Unenhanced CT imaging is highly sensitive to exclude pheochromocytoma: a multicenter study.

PubMed

Buitenwerf, Edward; Korteweg, Tijmen; Visser, Anneke; Haag, Charlotte M S C; Feelders, Richard A; Timmers, Henri J L M; Canu, Letizia; Haak, Harm R; Bisschop, Peter H L T; Eekhoff, Elisabeth M W; Corssmit, Eleonora P M; Krak, Nanda C; Rasenberg, Elise; van den Bergh, Janneke; Stoker, Jaap; Greuter, Marcel J W; Dullaart, Robin P F; Links, Thera P; Kerstens, Michiel N

2018-05-01

A substantial proportion of all pheochromocytomas is currently detected during the evaluation of an adrenal incidentaloma. Recently, it has been suggested that biochemical testing to rule out pheochromocytoma is unnecessary in case of an adrenal incidentaloma with an unenhanced attenuation value ≤10 Hounsfield Units (HU) at computed tomography (CT). We aimed to determine the sensitivity of the 10 HU threshold value to exclude a pheochromocytoma. Retrospective multicenter study with systematic reassessment of preoperative unenhanced CT scans performed in patients in whom a histopathologically proven pheochromocytoma had been diagnosed. Unenhanced attenuation values were determined independently by two experienced radiologists. Sensitivity of the 10 HU threshold was calculated, and interobserver consistency was assessed using the intraclass correlation coefficient (ICC). 214 patients were identified harboring a total number of 222 pheochromocytomas. Maximum tumor diameter was 51 (39-74) mm. The mean attenuation value within the region of interest was 36 ± 10 HU. Only one pheochromocytoma demonstrated an attenuation value ≤10 HU, resulting in a sensitivity of 99.6% (95% CI: 97.5-99.9). ICC was 0.81 (95% CI: 0.75-0.86) with a standard error of measurement of 7.3 HU between observers. The likelihood of a pheochromocytoma with an unenhanced attenuation value ≤10 HU on CT is very low. The interobserver consistency in attenuation measurement is excellent. Our study supports the recommendation that in patients with an adrenal incidentaloma biochemical testing for ruling out pheochromocytoma is only indicated in adrenal tumors with an unenhanced attenuation value >10 HU. © 2018 European Society of Endocrinology.

Incidental Findings in Abdominal Dual-Energy Computed Tomography: Correlation Between True Noncontrast and Virtual Noncontrast Images Considering Renal and Liver Cysts and Adrenal Masses.

PubMed

Slebocki, Karin; Kraus, Bastian; Chang, De-Hua; Hellmich, Martin; Maintz, David; Bangard, Christopher

To assess correlation between attenuation measurements of incidental findings in abdominal second generation dual-energy computed tomography (CT) on true noncontrast (TNC) and virtual noncontrast (VNC) images. Sixty-three patients underwent arterial dual-energy CT (Somatom Definition Flash, Siemens; pitch factor, 0.75-1.0; gantry rotation time, 0.28 seconds) after endovascular aneurysm repair, consisting of a TNC single energy CT scan (collimation, 128 × 0.6 mm; 120 kVp) and a dual-energy arterial phase scan (collimation, 32 × 0.6 mm, 140 and 100 kVp; blended, 120 kVp data set). Attenuation measurements in Hounsfield units (HU) of liver parenchyma and incidental findings like renal and hepatic cysts and adrenal masses on TNC and VNC images were done by drawing regions of interest. Statistical analysis was performed by paired t test and Pearson correlation. Incidental findings were detected in 56 (89%) patients. There was excellent correlation for both renal (n = 40) and hepatic cysts (n = 12) as well as adrenal masses (n = 6) with a Pearson correlation of 0.896, 0.800, and 0.945, respectively, and mean attenuation values on TNC and VNC images of 10.6 HU ± 12.8 versus 5.1 HU ± 17.5 (attenuation value range from -8.8 to 59.1 HU vs -11.8 to 73.4 HU), 6.4 HU ± 5.8 versus 6.3 HU ± 4.6 (attenuation value range from 2.0 to 16.2 HU vs -3.0 to 15.9 HU), and 12.8 HU ± 11.2 versus 12.4 HU ± 10.2 (attenuation value range from -2.3 to 27.5 HU vs -2.2 to 23.6 HU), respectively. As proof of principle, liver parenchyma measurements also showed excellent correlation between TNC and VNC (n = 40) images with a Pearson correlation of 0.839 and mean attenuation values on TNC and VNC images of 47.2 HU ± 10.5 versus 43.8 HU ± 8.7 (attenuation value range from 21.9 to 60.2 HU vs 4.5 to 65.3 HU). In conclusion, attenuation measurements of incidental findings like renal cysts or adrenal masses on TNC and VNC images derived from second generation dual-energy CT scans show excellent correlation providing considerable dose savings, favorable for future application in clinical routine.

TU-H-207A-03: CT Hounsfield Unit Accuracy: Effect of Beam Hardening On Phantom and Clinical Whole-Body CT Images

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ai, H; Wendt, R

2016-06-15

Purpose: To assess the effect of beam hardening on measured CT HU values. Methods: An anthropomorphic knee phantom was scanned with the CT component of a GE Discovery 690 PET/CT scanner (120kVp, 300mAs, 40?0.625mm collimation, pitch=0.984, FOV=500mm, matrix=512?512) with four different scan setups, each of which induces different degrees of beam hardening by introducing additional attenuation media into the field of view. Homogeneous voxels representing “soft tissue” and “bone” were segmented by HU thresholding followed by a 3D morphological erosion operation which removes the non-homogenous voxels located on the interface of thresholded tissue mask. HU values of segmented “soft tissue”more » and “bone” were compared.Additionally, whole-body CT data with coverage from the skull apex to the end of toes were retrospectively retrieved from seven PET/CT exams to evaluate the effect of beam hardening in vivo. Homogeneous bone voxels were segmented with the same method previously described. Total In-Slice Attenuation (TISA) for each CT slice, defined as the summation of HU values over all voxels within a CT slice, was calculated for all slices of the seven whole-body CT datasets and evaluated against the mean HU values of homogeneous bone voxels within that slice. Results: HU values measured from the phantom showed that while “soft tissue” HU values were unaffected, added attenuation within the FOV caused noticeable decreases in the measured HU values of “bone” voxels. A linear relationship was observed between bone HU and TISA for slices of the torso and legs, but not of the skull. Conclusion: Beam hardening effect is not an issue of concern for voxels with HU in the soft tissue range, but should not be neglected for bone voxels. A linear relationship exists between bone HU and the associated TISA in non-skull CT slices, which can be exploited to develop a correction strategy.« less

Effect of various refrigeration temperatures on quality of shell eggs.

PubMed

Shin, Daekeun; Narciso-Gaytán, Carlos; Regenstein, Joe M; Sánchez-Plata, Marcos X

2012-05-01

The objective of this study was to evaluate the effects of low storage temperatures on shell egg quality. Approximately 2100 shell eggs were collected and stored at - 1.1, 0.6, 2.2, 3.9, 5.6 and 7.2 °C for up to 4 weeks. Eighteen eggs at each storage temperature were evaluated after 0, 2, 7, 14, 21 and 28 days of storage. Haugh units (HU), yolk index (YI), albumen pH (pHA), yolk pH (pHY) and angel food cake density (CD) were measured. Shell egg quality tended to be preserved better at below 2.2 °C, as high HU and YI values relative to eggs stored at 7.2 °C were determined on day 28. However, storage at - 1.1 °C tended to cause the opposite effect, especially highly declined HU values over time. Significantly different HU values of shell eggs were measured after 14 days of storage, with eggs stored at 0.6 and 2.2 °C having the highest HU values, 80.42 and 77.97 respectively. A lower temperature limit for shell egg storage could be established between 0.6 and 2.2 °C, as both temperatures showed the highest HU values, 77.88 and 77.60 respectively, after 28 days of storage. Copyright © 2011 Society of Chemical Industry.

Usefulness of hounsfield unit and density in the assessment and treatment of urinary stones

PubMed Central

Gücük, Adnan; Üyetürk, Uğur

2014-01-01

Computed tomography (CT) is widely used to examine stones in the urinary system. In addition to the size and location of the stone and the overall health of the kidney, CT can also assess the density of the stone in Hounsfield units (HU). The HU, or Hounsfield density, measured by CT, is related to the density of the tissue or stone. A number of studies have assessed the use of HU in urology. HUs have been used to predict the type and opacity of stones during diagnosis, and the efficacy has been assessed using methods including extracorporeal shock wave lithotripsy (ESWL), percutaneous nephrolithotomy (PCNL), ureterorenoscopic ureterolithotripsy (URSL), and medical expulsive treatment (MET). Previous studies have focused on the success rate of HU for predicting the type of stone and of ESWL treatment. Understanding the composition of the stone plays a key role in determining the most appropriate treatment modality. The most recent reports have suggested that the HU value and its variants facilitate prediction of stone composition. However, the inclusion of data regarding urine, such as pH and presence of crystals, increases the predictive accuracy. HUs, which now form part of the clinical guidelines, allow us to predict the success of ESWL; therefore, they should be taken into account when ESWL is considered as a treatment option. However, there are currently insufficient data available regarding the value of HU for assessing the efficacy of PCNL, URSL, and MET. Studies performed to date suggest that these values would make a significant contribution to the diagnosis and treatment of urinary system stones. However, more data are required to assess this further. PMID:25374823

Effect of object location on the density measurement and Hounsfield conversion in a NewTom 3G cone beam computed tomography unit.

PubMed

Lagravère, M O; Carey, J; Ben-Zvi, M; Packota, G V; Major, P W

2008-09-01

The purpose of this study was to determine the effect of an object's location in a cone beam CT imaging chamber (CBCT-NewTom 3G) on its apparent density and to develop a linear conversion coefficient for Hounsfield units (HU) to material density (g cm(-3)) for the NewTom 3G Scanner. Three cylindrical models of materials with different densities were constructed and scanned at five different locations in a NewTom 3G Volume Scanner. The average HU value for each model at each location was obtained using two different types of software. Next, five cylinders of different known densities were scanned at the exact centre of a NewTom 3G Scanner. The collected data were analysed using the same two types of software to determine a standard linear relationship between density and HU for each type of software. There is no statistical significance of location of an object within the CBCT scanner on determination of its density. A linear relationship between the density of an object and the HU of a scan was rho = 0.001(HU)+1.19 with an R2 value of 0.893 (where density, rho, is measured in g cm(-3)). This equation is to be used on a range between 1.42 g cm(-3) and 0.4456 g cm(-3). A linear relationship can be used to determine the density of materials (in the density range of bone) from the HU values of a CBCT scan. This relationship is not affected by the object's location within the scanner itself.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Grzetic, S; Weldon, M; Noa, K

Purpose: This study compares the newly released MaxFOV Revision 1 EFOV reconstruction algorithm for GE RT590 to the older WideView EFOV algorithm. Two radiotherapy overlays from Q-fix and Diacor, are included in our analysis. Hounsfield Units (HU) generated with the WideView algorithm varied in the extended field (beyond 50cm) and the scanned object’s border varied from slice to slice. A validation of HU consistency between the two reconstruction algorithms is performed. Methods: A CatPhan 504 and CIRS062 Electron Density Phantom were scanned on a GE RT590 CT-Simulator. The phantoms were positioned in multiple locations within the scan field of viewmore » so some of the density plugs were outside the 50cm reconstruction circle. Images were reconstructed using both the WideView and MaxFOV algorithms. The HU for each scan were characterized both in average over a volume and in profile. Results: HU values are consistent between the two algorithms. Low-density material will have a slight increase in HU value and high-density material will have a slight decrease in HU value as the distance from the sweet spot increases. Border inconsistencies and shading artifacts are still present with the MaxFOV reconstruction on the Q-fix overlay but not the Diacor overlay (It should be noted that the Q-fix overlay is not currently GE-certified). HU values for water outside the 50cm FOV are within 40HU of reconstructions at the sweet spot of the scanner. CatPhan HU profiles show improvement with the MaxFOV algorithm as it approaches the scanner edge. Conclusion: The new MaxFOV algorithm improves the contour border for objects outside of the standard FOV when using a GE-approved tabletop. Air cavities outside of the standard FOV create inconsistent object borders. HU consistency is within GE specifications and the accuracy of the phantom edge improves. Further adjustments to the algorithm are being investigated by GE.« less

SU-E-I-17: Evaluation of Commercially Available Extension Plates for the ACR CT Accreditation Phantom

DOE Office of Scientific and Technical Information (OSTI.GOV)

Greene-Donnelly, K; Ogden, K

Purpose: To evaluate the impact of commercially available extension plates on Hounsfield Unit (HU) values in the ACR CT accreditation phantom (Model 464, Gammex Inc., Middleton, Wi). The extension plates are intended to improve water HU values in scanners where the traditional solution involves scanning the phantom with an adjacent water or CTDI phantom. Methods: The Model 464 phantom was scanned on 9 different CT scanners at 8 separate sites representing 16 and 64 slice MDCT technology from four CT manufacturers. The phantom was scanned with and without the extension plates (Gammex 464 EXTPLT-KIT) in helical and axial modes. Amore » water phantom was also scanned to verify water HU calibration. Technique was 120 kV tube potential, 350 mAs, and 210 mm display field of view. Slice thickness and reconstruction algorithm were based on site clinical protocols. The widest available beam collimation was used. Regions of interest were drawn on the HU test objects in Module 1 of the phantom and mean values recorded. Results: For all axial mode scans, water HU values were within limits with or without the extension plates. For two scanners (both Lightspeed VCT, GE Medical Systems, Waukesha WI), axial mode bone HU values were above the specified range both with and without the extension plates though they were closer to the specified range with the plates installed. In helical scan mode, two scanners (both GE Lightspeed VCT) had water HU values above the specified range without the plates installed. With the plates installed, the water HU values were within range for all scanners in all scan modes. Conclusion: Using the plates, the Lightspeed VCT scanners passed the water HU test when scanning in helical mode. The benefit of the extension plates was evident in helical mode scanning with GE scanners using a nominal 4 cm beam. Disclosure: The extension plates evaluated in this work were provided free of charge to the authors. The authors have no other financial interest in Gammex Inc.« less

Ultralow dose dentomaxillofacial CT imaging and iterative reconstruction techniques: variability of Hounsfield units and contrast-to-noise ratio

PubMed Central

Bischel, Alexander; Stratis, Andreas; Kakar, Apoorv; Bosmans, Hilde; Jacobs, Reinhilde; Gassner, Eva-Maria; Puelacher, Wolfgang; Pauwels, Ruben

2016-01-01

Objective: The aim of this study was to evaluate whether application of ultralow dose protocols and iterative reconstruction technology (IRT) influence quantitative Hounsfield units (HUs) and contrast-to-noise ratio (CNR) in dentomaxillofacial CT imaging. Methods: A phantom with inserts of five types of materials was scanned using protocols for (a) a clinical reference for navigated surgery (CT dose index volume 36.58 mGy), (b) low-dose sinus imaging (18.28 mGy) and (c) four ultralow dose imaging (4.14, 2.63, 0.99 and 0.53 mGy). All images were reconstructed using: (i) filtered back projection (FBP); (ii) IRT: adaptive statistical iterative reconstruction-50 (ASIR-50), ASIR-100 and model-based iterative reconstruction (MBIR); and (iii) standard (std) and bone kernel. Mean HU, CNR and average HU error after recalibration were determined. Each combination of protocols was compared using Friedman analysis of variance, followed by Dunn's multiple comparison test. Results: Pearson's sample correlation coefficients were all >0.99. Ultralow dose protocols using FBP showed errors of up to 273 HU. Std kernels had less HU variability than bone kernels. MBIR reduced the error value for the lowest dose protocol to 138 HU and retained the highest relative CNR. ASIR could not demonstrate significant advantages over FBP. Conclusions: Considering a potential dose reduction as low as 1.5% of a std protocol, ultralow dose protocols and IRT should be further tested for clinical dentomaxillofacial CT imaging. Advances in knowledge: HU as a surrogate for bone density may vary significantly in CT ultralow dose imaging. However, use of std kernels and MBIR technology reduce HU error values and may retain the highest CNR. PMID:26859336

Quantitative analysis of computed tomography images and early detection of cerebral edema for pediatric traumatic brain injury patients: retrospective study.

PubMed

Kim, Hakseung; Kim, Gwang-dong; Yoon, Byung C; Kim, Keewon; Kim, Byung-Jo; Choi, Young Hun; Czosnyka, Marek; Oh, Byung-Mo; Kim, Dong-Joo

2014-10-22

The purpose of this study was to identify whether the distribution of Hounsfield Unit (HU) values across the intracranial area in computed tomography (CT) images can be used as an effective diagnostic tool for determining the severity of cerebral edema in pediatric traumatic brain injury (TBI) patients. CT images, medical records and radiology reports on 70 pediatric patients were collected. Based on radiology reports and the Marshall classification, the patients were grouped as mild edema patients (n=37) or severe edema patients (n=33). Automated quantitative analysis using unenhanced CT images was applied to eliminate artifacts and identify the difference in HU value distribution across the intracranial area between these groups. The proportion of pixels with HU=17 to 24 was highly correlated with the existence of severe cerebral edema (P<0.01). This proportion was also able to differentiate patients who developed delayed cerebral edema from mild TBI patients. A significant difference between deceased patients and surviving patients in terms of the HU distribution came from the proportion of pixels with HU=19 to HU=23 (P<0.01). The proportion of pixels with an HU value of 17 to 24 in the entire cerebral area of a non-enhanced CT image can be an effective basis for evaluating the severity of cerebral edema. Based on this result, we propose a novel approach for the early detection of severe cerebral edema.

Albeni Falls Wildlife Protection, Mitigation, and Enhancement Plan, Final Report 1987.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Martin, Robert C.

1988-08-01

A wildlife impact assessment and mitigation plan has been developed for the US Army Corps of Engineers Albeni Falls Project in northern Idaho. The Habitat Evaluation Procedure (HEP) was used to evaluate pre- and post-construction habitat conditions at the Albeni Falls Project. There were 6617 acres of wetlands converted to open water due to development and operation of the project. Eight evaluation species were selected with impacts expressed in numbers of Habitat Units (HU's). For a given species, one HU is equivalent to one acre of prime habitat. The Albeni Falls Project resulted in estimated losses of 5985 mallard HU's,more » 4699 Canada goose HU's, 3379 redhead HU's, 4508 breeding bald eagle HU's, 4365 wintering bald eagle HU's, 2286 black-capped chickadee HU's, 1680 white-tailed deer HU's, and 1756 muskrat HU's. The yellow warbler gained 71 HU's. Therefore, total target species estimated impacts were 28,587 HU's. Impacts on peregrine falcons were not quantified in terms of HU's. Projects have been proposed by an interagency team of biologists to mitigate the impacts of Albeni Falls on wildlife. The HEP was used to estimate benefits of proposed mitigation projects to target species. Through a series of proposed protection and enhancement actions, the mitigation plan will provide benefits of an estimated 28,590 target species HU's to mitigate Albeni Falls wildlife habitat values lost. 52 refs., 9 figs., 14 tabs.« less

Adrenocortical tumours: high CT attenuation value correlates with eosinophilia but does not discriminate lipid-poor adenomas from malignancy.

PubMed

Pennanen, Mirkka; Raade, Merja; Louhimo, Johanna; Sane, Timo; Heiskanen, Ilkka; Arola, Johanna; Haglund, Caj

2013-12-01

Characterisation of adrenal tumours is an important clinical problem. Unenhanced CT is the primary imaging modality to assess the nature of these lesions. To study the correlation between unenhanced CT attenuation value and the specific histopathology, as well as the proportion of lipid-poor eosinophilic cells in adrenocortical tumours. We studied retrospectively primary adrenocortical tumours that had been operated on at Helsinki University Central Hospital between 2002 and 2008. Of 171 tumours, 79 had appropriate preoperative CT scans and were included in the study. We evaluated the unenhanced CT attenuation values (Hounsfield units, HU) of these tumours and determined their histopathological diagnosis by the Weiss scoring system. We also assessed the proportion of lipid-poor eosinophilic cells for each tumour. Unenhanced CT attenuation value (HU) in adrenocortical tumours correlated well with the proportion of lipid-poor eosinophilic cells (rs=0.750, p<0.001). HU and Weiss score also had a correlation (rs=0.582, p<0.001). Unenhanced CT attenuation value correlates well with the percentage of lipid-poor eosinophilic cells, but unenhanced CT attenuation value fails to differentiate between benign lipid-poor adenomas and malignant adrenocortical tumours. All adrenocortical tumours with unenhanced CT attenuation value ≤10 HU are histologically benign lipid-rich tumours.

WE-AB-202-06: Correlating Lung CT HU with Transformation-Based and Xe-CT Derived Ventilation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Du, K; Patton, T; Bayouth, J

Purpose: Regional lung ventilation is useful to reduce radiation-induced function damage during lung cancer radiation therapy. Recently a new direct HU (Hounsfield unit)-based method was proposed to estimate the ventilation potential without image registration. The purpose of this study is to examine if there is a functional dependence between HU values and transformation-based or Xe-CT derived ventilation. Methods: 4DCT images acquired from 13 patients prior to radiation therapy and 4 mechanically ventilated sheep subjects which also have associated Xe-CT images were used for this analysis. Transformation-based ventilation was computed using Jacobian determinant of the transformation field between peak-exhale and peak-inhalemore » 4DCT images. Both transformation and Xe-CT derived ventilation was computed for each HU bin. Color scatter plot and cumulative histogram were used to compare and validate the direct HU-based method. Results: There was little change of the center and shape of the HU histograms between free breathing CT and 4DCT average, with or without smoothing, and between the repeated 4DCT scans. HU of −750 and −630 were found to have the greatest transformation-based ventilation for human and sheep subjects, respectively. Maximum Xe-CT derived ventilation was found to locate at HU of −600 in sheep subjects. The curve between Xe-CT ventilation and HU was noisy for tissue above HU −400, possibly due to less intensity change of Xe gas during wash-out and wash-in phases. Conclusion: Both transformation-based and Xe-CT ventilation demonstrated that lung tissues with HU values in the range of (-750, −600) HU have the maximum ventilation potential. The correlation between HU and ventilation suggests that HU might be used to help guide the ventilation calculation and make it more robust to noise and image registration errors. Research support from NIH grants CA166703 and CA166119 and a gift from Roger Koch.« less

Quantitative computed tomography of lung parenchyma in patients with emphysema: analysis of higher-density lung regions

NASA Astrophysics Data System (ADS)

Lederman, Dror; Leader, Joseph K.; Zheng, Bin; Sciurba, Frank C.; Tan, Jun; Gur, David

2011-03-01

Quantitative computed tomography (CT) has been widely used to detect and evaluate the presence (or absence) of emphysema applying the density masks at specific thresholds, e.g., -910 or -950 Hounsfield Unit (HU). However, it has also been observed that subjects with similar density-mask based emphysema scores could have varying lung function, possibly indicating differences of disease severity. To assess this possible discrepancy, we investigated whether density distribution of "viable" lung parenchyma regions with pixel values > -910 HU correlates with lung function. A dataset of 38 subjects, who underwent both pulmonary function testing and CT examinations in a COPD SCCOR study, was assembled. After the lung regions depicted on CT images were automatically segmented by a computerized scheme, we systematically divided the lung parenchyma into different density groups (bins) and computed a number of statistical features (i.e., mean, standard deviation (STD), skewness of the pixel value distributions) in these density bins. We then analyzed the correlations between each feature and lung function. The correlation between diffusion lung capacity (DLCO) and STD of pixel values in the bin of -910HU <= PV < -750HU was -0.43, as compared with a correlation of -0.49 obtained between the post-bronchodilator ratio (FEV1/FVC) measured by the forced expiratory volume in 1 second (FEV1) dividing the forced vital capacity (FVC) and the STD of pixel values in the bin of -1024HU <= PV < -910HU. The results showed an association between the distribution of pixel values in "viable" lung parenchyma and lung function, which indicates that similar to the conventional density mask method, the pixel value distribution features in "viable" lung parenchyma areas may also provide clinically useful information to improve assessments of lung disease severity as measured by lung functional tests.

A Quantitative Approach to Distinguish Pneumonia From Atelectasis Using Computed Tomography Attenuation.

PubMed

Edwards, Rachael M; Godwin, J David; Hippe, Dan S; Kicska, Gregory

2016-01-01

It is known that atelectasis demonstrates greater contrast enhancement than pneumonia on computed tomography (CT). However, the effectiveness of using a Hounsfield unit (HU) threshold to distinguish pneumonia from atelectasis has never been shown. The objective of the study is to demonstrate that an HU threshold can be quantitatively used to effectively distinguish pneumonia from atelectasis. Retrospectively identified CT pulmonary angiogram examinations that did not show pulmonary embolism but contained nonaerated lungs were classified as atelectasis or pneumonia based on established clinical criteria. The HU attenuation was measured in these nonaerated lungs. Receiver operating characteristic (ROC) analysis was performed to determine the area under the ROC curve, sensitivity, and specificity of using the attenuation to distinguish pneumonia from atelectasis. Sixty-eight nonaerated lungs were measured in 55 patients. The mean (SD) enhancement was 62 (18) HU in pneumonia and 119 (24) HU in atelectasis (P < 0.001). A threshold of 92 HU diagnosed pneumonia with 97% sensitivity (confidence interval [CI], 80%-99%) and 85% specificity (CI, 70-93). Accuracy, measured as area under the ROC curve, was 0.97 (CI, 0.89-0.99). We have established that a threshold HU value can be used to confidently distinguish pneumonia from atelectasis with our standard CT pulmonary angiogram imaging protocol and patient population. This suggests that a similar threshold HU value may be determined for other scanning protocols, and application of this threshold may facilitate a more confident diagnosis of pneumonia and thus speed treatment.

TH-CD-202-06: A Method for Characterizing and Validating Dynamic Lung Density Change During Quiet Respiration

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dou, T; Ruan, D; Heinrich, M

2016-06-15

Purpose: To obtain a functional relationship that calibrates the lung tissue density change under free breathing conditions through correlating Jacobian values to the Hounsfield units. Methods: Free-breathing lung computed tomography images were acquired using a fast helical CT protocol, where 25 scans were acquired per patient. Using a state-of-the-art deformable registration algorithm, a set of the deformation vector fields (DVF) was generated to provide spatial mapping from the reference image geometry to the other free-breathing scans. These DVFs were used to generate Jacobian maps, which estimate voxelwise volume change. Subsequently, the set of 25 corresponding Jacobian and voxel intensity inmore » Hounsfield units (HU) were collected and linear regression was performed based on the mass conservation relationship to correlate the volume change to density change. Based on the resulting fitting coefficients, the tissues were classified into parenchymal (Type I), vascular (Type II), and soft tissue (Type III) types. These coefficients modeled the voxelwise density variation during quiet breathing. The accuracy of the proposed method was assessed using mean absolute difference in HU between the CT scan intensities and the model predicted values. In addition, validation experiments employing a leave-five-out method were performed to evaluate the model accuracy. Results: The computed mean model errors were 23.30±9.54 HU, 29.31±10.67 HU, and 35.56±20.56 HU, respectively, for regions I, II, and III, respectively. The cross validation experiments averaged over 100 trials had mean errors of 30.02 ± 1.67 HU over the entire lung. These mean values were comparable with the estimated CT image background noise. Conclusion: The reported validation experiment statistics confirmed the lung density modeling during free breathing. The proposed technique was general and could be applied to a wide range of problem scenarios where accurate dynamic lung density information is needed. This work was supported in part by NIH R01 CA0096679.« less

SU-G-IeP2-12: The Effect of Iterative Reconstruction and CT Tube Voltage On Hounsfield Unit Values of Iodinated Contrast

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ogden, K; Greene-Donnelly, K; Vallabhaneni, D

Purpose: To investigate the effects of changing iterative reconstruction strength and tube voltage on Hounsfield Unit (HU) values of varying concentrations of Iodinated contrast medium in a phantom. Method: Iodinated contrast (Omnipaque 300, GE Healthcare, Princeton NJ) was diluted with distilled water to concentrations of 0.6, 0.9, 1.8, 3.6, 7.2, and 10.8 mg/mL of Iodine. The solutions were scanned in a patient equivalent water phantom on two MDCT scanners: VCT 64 slice (GE Medical Systems, Waukesha, WI) and an Aquilion One 320 slice scanner (Toshiba America Medical Systems, Tustin CA). The phantom was scanned at 80, 100, 120, 140 kVmore » using 400, 255, 180, and 130 mAs, respectively, for the VCT scanner, and 80, 100, 120, and 135 kV using 400, 250, 200, and 150 mAs, respectively, on the Aquilion One. Images were reconstructed at 2.5 mm (VCT) and 0.5 mm (Aquilion One). The VCT images were reconstructed using Advanced Statistical Iterative Reconstruction (ASIR) at 6 different strengths: 0%, 20%, 40%, 60%, 80%, and 100%. Aquilion One images were reconstructed using Adaptive Iterative Dose Reduction (AIDR) at 4 strengths: no AIDR, Weak AIDR, Standard AIDR, and Strong AIDR. Regions of interest (ROIs) were drawn on the images to measure the HU values and standard deviations of the diluted contrast. Second order polynomials were used to fit the HU values as a function of Iodine concentration. Results: For both scanners, there was no significant effect of changing the iterative reconstruction strength. The polynomial fits yielded goodness-of-fit (R2) values averaging 0.997. Conclusion: Changing the strength of the iterative reconstruction has no significant effect on the HU values of Iodinated contrast in a tissue-equivalent phantom. Fit values of HU vs Iodine concentration are useful in quantitative imaging protocols such as the determination of cardiac output from time-density curves in the main pulmonary artery.« less

Variability of runoff-based drought conditions in the conterminous United States

USGS Publications Warehouse

McCabe, Gregory J.; Wolock, David M.; Austin, Samuel H.

2017-01-01

In this study, a monthly water-balance model is used to simulate monthly runoff for 2109 hydrologic units (HUs) in the conterminous United States (CONUS) for water-years 1901 through 2014. The monthly runoff time series for each HU were smoothed with a 3-month moving average, and then the 3-month moving-average runoff values were converted to percentiles. For each HU, a drought was considered to occur when the HU runoff percentile dropped to the 20th percentile or lower. A drought was considered to end when the HU runoff percentile exceeded the 20th percentile. After identifying drought events for each HU, the frequency and length of drought events were examined. Results indicated that (1) the longest mean drought lengths occur in the eastern CONUS and parts of the Rocky Mountain region and the northwestern CONUS, (2) the frequency of drought is highest in the southwestern and central CONUS, and lowest in the eastern CONUS, the Rocky Mountain region, and the northwestern CONUS, (3) droughts have occurred during all months of the year and there does not appear to be a seasonal pattern to drought occurrence, (4) the variability of precipitation appears to have been the principal climatic factor determining drought, and (5) for most of the CONUS, drought frequency appears to have decreased during the 1901 through 2014 period.

Increased red cell 2,3-diphosphoglycerate levels in haemodialysis patients treated with erythropoietin.

PubMed

Horina, J H; Schwaberger, G; Brussee, H; Sauseng-Fellegger, G; Holzer, H; Krejs, G J

1993-01-01

The efficacy of recombinant human erythropoietin (rHuEpo) for the treatment of renal anaemia is well established. To assess the effect of rHuEpo treatment on physical performance we evaluated physical working capacity, oxygen uptake and red cell 2,3-diphosphoglycerate (DPG) values at rest and during and after exercise on a bicycle spiroergometer in eight chronically haemodialysed patients. Follow-up examination was carried out after a mean of 14 weeks (range 9-19 weeks), when mean haemoglobin had increased from 7.8 to a stable value of 13.0 g/dl in response to rHuEpo treatment (P < 0.001). Physical working capacity and oxygen uptake at the anaerobic threshold (4 mmol/l blood lactate concentration) increased from 68 +/- 12 to 80 +/- 16 watts and 0.95 +/- 0.14 to 1.10 +/- 0.20 l/min, respectively (P < 0.01). DPG, which determines oxygen affinity to haemoglobin in red cells, increased by 13% from 13.7 +/- 1.5 to 15.5 +/- 2.2 mumol/g Hb (P < 0.05). With maximal exercise mean DPG values significantly decreased to a much lower level without rHuEpo treatment than after correction of anaemia. Therefore rHuEpo treatment results both in better oxygen transport capacity and reduced intraerythrocytic oxygen affinity, which is followed by improved oxygen delivery to tissues per unit of haemoglobin. These effects may explain the improvement of exercise capacity observed in dialysis patients after rHuEpo treatment.

Ability of calibration phantom to reduce the interscan variability in electron beam computed tomography.

PubMed

Budoff, Matthew J; Mao, Songshou; Lu, Bin; Takasu, Junichiro; Child, Janis; Carson, Sivi; Fisher, Hans

2002-01-01

To test the hypothesis that a calibration phantom would improve interpatient and interscan variability in coronary artery calcium (CAC) studies. We scanned 144 patients twice with or without the calibration phantom and then scanned 93 patients with a single calcific lesion twice and, finally, scanned a cork heart with calcific foci. There were no linear correlations in computed tomography Hounsfield unit (CT HU) and CT HU interscan variation between blood pool and phantom plugs at any slice level in patient groups (p > 0.05). The CT HU interscan variation in phantom plugs (2.11 HU) was less than that of the blood pool (3.47 HU; p < 0.05) and CAC lesion (20.39; p < 0.001). Comparing images with and without a calibration phantom, there was a significant decrease in CT HU as well as an increase in noise and peak values in patient studies and the cork phantom study. The CT HU attenuation variations of the interpatient and interscan blood pool, calibration phantom plug, and cork coronary arteries were not parallel. Therefore, the ability to adjust the CT HU variation of calcific lesions by a calibration phantom is problematic and may worsen the problem.

Quantitative analysis of pulmonary pathophysiology using postmortem computed tomography with regard to the cause of death.

PubMed

Michiue, Tomomi; Sakurai, Terumi; Ishikawa, Takaki; Oritani, Shigeki; Maeda, Hitoshi

2012-07-10

Radiological lung transparency depends on the air contents involved in respiratory function. The present study quantitatively investigated postmortem lung air distribution in forensic autopsy cases (n=135) using computed tomography (CT) to analyze cardiopulmonary pathophysiology in the death process, involving emphysema, congestion and edema. Combined analyses of the CT morphology and attenuation value (Hounsfield unit, HU) of the bilateral lungs, with reference to histopathology, could categorize CT findings (10-90 percentile mode/mean HU values) with regard to the causes of death as follows: (I) hyperaeration (mode/mean HU below -760/-560: emphysema) for obstructive pulmonary disease, starvation and hypothermia (cold exposure); (II) mostly normal aeration with partial ground glass opacification (mode/mean HU, -850 to -360/-700 to -380: partial congestion and edema), consisting of subtype II-a with peri-bronchial/-vascular opacity for mechanical asphyxia, drowning and fire fatality, and subtype II-b with decreased vascularity for gunshot head injury, cerebrovascular disease and hemopericardium; (III) hypoaeration to airless with predominant hypostatic ground glass opacification (mode/mean HU, -870 to 0/-720 to -200: mottled hypostatic congestion and edema) for blunt head/neck injury, intoxication, hyperthermia (heat stroke) and congestive heart failure; (IV) hypoaeration to airless with predominant hypostatic consolidation (mode/mean HU, -790 to 0/-520 to -70: intense hypostatic congestion with edema) for acute ischemic heart disease; and (V) airless to consolidated (mode/mean HU over -420/-370: segmental or multiple patchy consolidations with edema) for pneumonia. Mode HU represents the major alveolar status, while the mean HU reflects the whole lung air contents. CT data analysis is useful for quantitative evaluation of pulmonary pathology as a supplementary procedure. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

X-ray attenuation of the liver and kidney in cats considered at varying risk of hepatic lipidosis.

PubMed

Lam, Richard; Niessen, Stijn J; Lamb, Christopher R

2014-01-01

X-ray attenuation of the liver has been measured using computed tomography (CT) and reported to decrease in cats with experimentally induced hepatic lipidosis. To assess the clinical utility of this technique, medical records and noncontrast CT scans of a series of cats were retrospectively reviewed. A total of 112 cats met inclusion criteria and were stratified into three hepatic lipidosis risk groups. Group 1 cats were considered low-risk based on no history of inappetence or weight loss, and normal serum chemistry values; Group 2 cats were considered intermediate risk based on weight loss, serum hepatic enzymes above normal limits, or reasonably controlled diabetes mellitus; and Group 3 cats were considered high risk based on poorly controlled diabetes mellitus due to hypersomatotropism. Mean CT attenuation values (Hounsfield units, HU) were measured using regions of interest placed within the liver and cranial pole of the right kidney. Hepatic and renal attenuation were weakly positively correlated with each other (r = 0.2, P = 0.03) and weakly negatively correlated with body weight (r = -0.21, P = 0.05, and r = -0.34, P = 0.001, respectively). Mean (SD) hepatic and renal cortical attenuation values were 70.7 (8.7) HU and 49.6 (9.2) HU for Group 1 cats, 71.4 (7.9) HU and 48.6 (9.1) HU for Group 2, and 68.9 (7.6) HU and 47.6 (7.2) HU for Group 3. There were no significant differences in hepatic or renal attenuation among groups. Findings indicated that CT measures of X-ray attenuation in the liver and kidney may not be accurate predictors of naturally occurring hepatic lipidosis in cats. © 2013 American College of Veterinary Radiology.

Efficacy of CT in diagnosis of transudates and exudates in patients with pleural effusion

PubMed Central

Çullu, Neşat; Kalemci, Serdar; Karakaş, Ömer; Eser, İrfan; Yalçın, Funda; Boyacı, Fatıma Nurefşan; Karakaş, Ekrem

2014-01-01

PURPOSE We aimed to evaluate the efficacy of multidetector computed tomography (CT) imaging in diagnosis of pleural exudates and transudates using attenuation values. MATERIALS AND METHODS This retrospective study included 106 patients who were diagnosed with pleural effusion between January 2010 and June 2012. After the patients underwent chest CT, thoracentesis was performed in the first week. The attenuation values of the pleural effusions were measured in all patients. RESULTS According to Light’s criteria, 30 of 106 patients with pleural effusions had transudates, and the remaining patients had exudates. The Hounsfield unit (HU) value of the exudates (median, 12.5; range, 4–33) was significantly higher than that of the transudates (median, 5; range, 2–15) (P = 0.001). Additionally, when evaluated by disease subgroups, congestive heart failure and empyema were predictable in terms of median HU values of the pleural effusions with high and moderate sensitivity and specificity values (84.6% and 81.2%, respectively; 76.9% and 66.7%, respectively). Compared with other patients, the empyema patients had significantly more loculation and pleural thickening. CONCLUSION CT attenuation values may be useful in differentiating exu-dates from transudates. Although there is an overlap in most effusions, exudate can be considered when the CT attenuation values are >15 HU. Because of overlapping HU values, close correlation with clinical findings is essential. Additional signs, such as fluid loculation and pleural thickness, should be considered and may provide further information for the differentiation. PMID:24100060

Efficacy of CT in diagnosis of transudates and exudates in patients with pleural effusion.

PubMed

Çullu, Neşat; Kalemci, Serdar; Karakaş, Ömer; Eser, İrfan; Yalçin, Funda; Boyacı, Fatıma Nurefşan; Karakaş, Ekrem

2014-01-01

We aimed to evaluate the efficacy of multidetector computed tomography (CT) imaging in diagnosis of pleural exudates and transudates using attenuation values. This retrospective study included 106 patients who were diagnosed with pleural effusion between January 2010 and June 2012. After the patients underwent chest CT, thoracentesis was performed in the first week. The attenuation values of the pleural effusions were measured in all patients. According to Light's criteria, 30 of 106 patients with pleural effusions had transudates, and the remaining patients had exudates. The Hounsfield unit (HU) value of the exudates (median, 12.5; range, 4-33) was significantly higher than that of the transudates (median, 5; range, 2-15) (P = 0.001). Additionally, when evaluated by disease subgroups, congestive heart failure and empyema were predictable in terms of median HU values of the pleural effusions with high and moderate sensitivity and specificity values (84.6% and 81.2%, respectively; 76.9% and 66.7%, respectively). Compared with other patients, the empyema patients had significantly more loculation and pleural thickening. CT attenuation values may be useful in differentiating exudates from transudates. Although there is an overlap in most effusions, exudate can be considered when the CT attenuation values are >15 HU. Because of overlapping HU values, close correlation with clinical findings is essential. Additional signs, such as fluid loculation and pleural thickness, should be considered and may provide further information for the differentiation.

TU-F-CAMPUS-J-01: Dosimetric Effects of HU Changes During the Course of Proton Therapy for Lung Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Teng, C; Yin, L; Ainsley, C

2015-06-15

Purpose: To characterize the changes in Hounsfield unit (HU) in lung radiotherapy with proton beams during the course of treatment and to study the effect on the proton plan dose distribution. Methods: Twenty consecutive patients with non-small cell lung cancer treated with proton radiotherapy who underwent multiple CT scans including the planning CT and weekly verification CTs were studied. HU histograms were computed for irradiated lung volumes in beam paths for all scans using the same treatment plan. Histograms for un-irradiated lung volume were used as control to characterize inter-scan variations. HU statistics were calculated for both irradiated and un-irradiatedmore » lung volumes for each patient scan. Further, multiple CT scans based on the same planning CT were generated by replacing the HU of the lung based on the verification CT scans HU values. Using the same beam arrangement, we created plans for each of the altered CT scans to study the dosimetric effect using the dose volume histogram. Results: Lung HU decreased for irradiated lung volume during the course of radiotherapy. The magnitude of this change increased with total irradiation dose. On average, HU changed by −53.8 in the irradiated volume. This change resulted in less than 0.5mm of beam overshoot in tissue for every 1cm beam traversed in the irradiated lung. The dose modification is about +3% for the lung, and less than +1% for the primary tumor. Conclusion: HU of the lung decrease throughout the course of radiation therapy. This change results in a beam overshoot (e.g. 3mm for 6cm of lung traversed) and causes a small dose modification in the overall plan. However, this overshoot does not affect the quality of plans since the margins used in planning, based on proton range uncertainty, are greater. HU needs to change by 150 units before re-planning is warranted.« less

A novel diagnostic method (spectral computed tomography of sacroiliac joints) for axial spondyloarthritis.

PubMed

Zhang, Ping; Yu, Kai Hu; Guo, Rui Min; Ran, Jun; Liu, Yao; Morelli, John; Runge, Val M; Li, Xiao Ming

2016-08-01

To evaluate the diagnostic value of spectral computed tomography (CT) of sacroiliac joints for axial spondyloarthritis (SpA). We retrospectively analyzed the records of 125 patients with low back pain (LBP) suspected of having SpA. Each patient underwent sacroiliac joint spectral CT examination. Water- and calcium-based material decomposition images were reconstructed. After 3-6 months of follow-up, 76 were diagnosed with SpA, and the remaining 49 patients were diagnosed with nonspecific LBP (nLBP). The slope of sacroiliac bone marrow HU (Hounsfield unit) curve (λHU), CT value, and bone marrow to normal muscle ratios of water and calcium concentrations in the ilium and sacrum were calculated and compared between nLBP and SpA patients. The iliac λHU was 8.26 ± 3.91 for nLBP and 9.81 ± 4.92 for SpA. The mean iliac ratios of water and calcium concentrations were 1.04 ± 0.03 and 21.67 ± 4.40, respectively, for nLBP, and 1.07 ± 0.04 and 111.5 ± 358.98, respectively, for SpA. The mean iliac CT values were 311.12 ± 86.52 HU for nLBP and 423.97 ± 127.51 HU for SpA. There were statistically significant differences in iliac ratios of water and calcium concentrations, CT value, and λHU between nLBP and SpA patients (p < 0.05). The sensitivity of iliac λHU was the highest. The diagnostic odds ratio of ratio of iliac calcium concentration was the highest, and its negative likelihood ratio was the lowest. Spectral CT not only shows bone erosion and sclerosis, but also shows and quantitatively measures bone marrow edema in the sacroiliac joints of SpA patients. Copyright © 2015. Published by Elsevier B.V.

Sensitivity of Hyperdense Basilar Artery Sign on Non-Enhanced Computed Tomography.

PubMed

Ernst, Marielle; Romero, Javier M; Buhk, Jan-Hendrik; Cheng, Bastian; Herrmann, Jochen; Fiehler, Jens; Groth, Michael

2015-01-01

The hyperdense basilar artery sign (HBAS) is an indicator of vessel occlusion on non contrast-enhanced computer tomography (NECT) in acute stroke patients. Since basilar artery occlusion (BAO) is associated with a high mortality and morbidity, its early detection is of great clinical value. We sought to analyze the influence of density measurement as well as a normalized ratio of Hounsfield unit/hematocrit (HU/Hct) ratio on the detection of BAO on NECT in patients with suspected BAO. 102 patients with clinically suspected BAO were examined with NECT followed immediately by Multidetector computed tomography Angiography. Two observers independently analyzed the images regarding the presence or absence of HBAS on NECT and performed HU measurements in the basilar artery. Receiver operating characteristic curve analysis was performed to determine the optimal density threshold for BAO using attenuation measurements or HU/Hct ratio. Sensitivity of visual detection of the HBAS on NECT was relatively low 81% (95%-CI, 54-95%) while specificity was high 91% (95%-CI, 82-96%). The highest sensitivity was achieved by the combination of visual assessment and additional quantitative attenuation measurements applying a cut-off value of 46.5 HU with 94% sensitivity and 81% specificity for BAO. A HU/Hct ratio >1.32 revealed sensitivity of 88% (95%-CI, 60-98%) and specificity of 84% (95%-CI, 74-90%). In patients with clinically suspected acute BAO the combination of visual assessment and additional attenuation measurement with a cut-off value of 46.5 HU is a reliable approach with high sensitivity in the detection of BAO on NECT.

The impact of smart metal artefact reduction algorithm for use in radiotherapy treatment planning.

PubMed

Guilfoile, Connor; Rampant, Peter; House, Michael

2017-06-01

The presence of metal artefacts in computed tomography (CT) create issues in radiation oncology. The loss of anatomical information and incorrect Hounsfield unit (HU) values produce inaccuracies in dose calculations, providing suboptimal patient treatment. Metal artefact reduction (MAR) algorithms were developed to combat these problems. This study provides a qualitative and quantitative analysis of the "Smart MAR" software (General Electric Healthcare, Chicago, IL, USA), determining its usefulness in a clinical setting. A detailed analysis was conducted using both patient and phantom data, noting any improvements in HU values and dosimetry with the GE-MAR enabled. This study indicates qualitative improvements in severity of the streak artefacts produced by metals, allowing for easier patient contouring. Furthermore, the GE-MAR managed to recover previously lost anatomical information. Additionally, phantom data showed an improvement in HU value with GE-MAR correction, producing more accurate point dose calculations in the treatment planning system. Overall, the GE-MAR is a useful tool and is suitable for clinical environments.

SU-E-J-210: Characterizing Tissue Equivalent Materials for the Development of a Dual MRI-CT Heterogeneous Anthropomorphic Phantom Designed Specifically for MRI Guided Radiotherapy Systems

DOE Office of Scientific and Technical Information (OSTI.GOV)

Steinmann, A; Stafford, R; Yung, J

Purpose: MRI guided radiotherapy (MRIgRT) is an emerging technology which will eventually require a proficient quality auditing system. Due to different principles in which MR and CT acquire images, there is a need for a multi-imaging-modality, end-to-end QA phantom for MRIgRT. The purpose of this study is to identify lung, soft tissue, and tumor equivalent substitutes that share similar human-like CT and MR properties (i.e. Hounsfield units and relaxation times). Methods: Materials of interested such as common CT QA phantom materials, and other proprietary gels/silicones from Polytek, SmoothOn, and CompositeOne were first scanned on a GE 1.5T Signa HDxT MR.more » Materials that could be seen on both T1-weighted and T2-weighted images were then scanned on a GE Lightspeed RT16 CT simulator and a GE Discovery 750HD CT scanner and their HU values were then measured. The materials with matching HU values of lung (−500 to −700HU), muscle (+40HU) and soft tissue (+100 to +300HU) were further scanned on GE 1.5T Signa HDx to measure their T1 and T2 relaxation times from varying parameters of TI and TE. Results: Materials that could be visualized on T1-weighted and T2-weighted images from a 1.5T MR unit and had an appropriate average CT number, −650, −685, 46,169, and 168 HUs were: compressed cork saturated with water, Polytek Platsil™ Gel-00 combined with mini styrofoam balls, radiotherapy bolus material, SmoothOn Dragon-Skin™ and SmoothOn Ecoflex™, respectively. Conclusion: Post processing analysis is currently being performed to accurately map T1 and T2 values for each material tested. From previous MR visualization and CT examinations it is expected that Dragon-Skin™, Ecoflex™ and bolus will have values consistent with tissue and tumor substitutes. We also expect compressed cork statured with water, and Polytek™-styrofoam combination to have approximate T1 and T2 values suitable for lung-equivalent materials.« less

Correlations between quantitative fat–water magnetic resonance imaging and computed tomography in human subcutaneous white adipose tissue

PubMed Central

Gifford, Aliya; Walker, Ronald C.; Towse, Theodore F.; Brian Welch, E.

2015-01-01

Abstract. Beyond estimation of depot volumes, quantitative analysis of adipose tissue properties could improve understanding of how adipose tissue correlates with metabolic risk factors. We investigated whether the fat signal fraction (FSF) derived from quantitative fat–water magnetic resonance imaging (MRI) scans at 3.0 T correlates to CT Hounsfield units (HU) of the same tissue. These measures were acquired in the subcutaneous white adipose tissue (WAT) at the umbilical level of 21 healthy adult subjects. A moderate correlation exists between MRI- and CT-derived WAT values for all subjects, R2=0.54, p<0.0001, with a slope of −2.6, (95% CI [−3.3,−1.8]), indicating that a decrease of 1 HU equals a mean increase of 0.38% FSF. We demonstrate that FSF estimates obtained using quantitative fat–water MRI techniques correlate with CT HU values in subcutaneous WAT, and therefore, MRI-based FSF could be used as an alternative to CT HU for assessing metabolic risk factors. PMID:26702407

Detection of attenuated plaque in stable angina with 64-multidetector computed tomography: a comparison with intravascular ultrasound.

PubMed

Jinzaki, Masahiro; Okabe, Teruo; Endo, Ayaka; Kawamura, Akio; Koga, Seiko; Yamada, Minoru; Fukuda, Keiichi; Kuribayashi, Sachio

2012-01-01

To clarify multidetector computed tomography (MDCT) findings of attenuated plaque detected by intravascular ultrasound (IVUS). One hundred and fifty-four patients with stable angina underwent MDCT before IVUS. The attenuated plaque was identified in the targeted artery with IVUS, and the same artery was analyzed with MDCT for the presence of a high density area (HDA) >130 Hounsfield units (HU), and a low density area (LDA) <30 HU. A HDA in attenuated plaque was compared with that in calcified plaque. Ten attenuated plaques and 15 calcified plaques were identified in 9 of 154 patients (males=9, 66.2 ± 9.5 years). Eight of the 10 attenuated plaques and all 15 calcified plaques were accompanied with a HDA on MDCT. The HDA ranged from 174 to 667 HU (mean 389.0 ± 148.3 HU) in the 8 attenuated plaques, and from 545 to 1,205 HU (mean 920.9 ± 215.9 HU) in 15 calcified plaques. There was a significant difference in CT density of the HDA between the attenuated and calcified plaque (P<0.001). All attenuated plaques contained LDA <30 HU in the portions without HDA. MDCT has the ability to demonstrate attenuated plaque as the combination of HDA (approximately 400 HU on average) and LDA <30 HU. The HDA can be differentiated from calcified plaque by its lower CT density value.

Quantitative assessment of scatter correction techniques incorporated in next generation dual-source computed tomography

NASA Astrophysics Data System (ADS)

Mobberley, Sean David

Accurate, cross-scanner assessment of in-vivo air density used to quantitatively assess amount and distribution of emphysema in COPD subjects has remained elusive. Hounsfield units (HU) within tracheal air can be considerably more positive than -1000 HU. With the advent of new dual-source scanners which employ dedicated scatter correction techniques, it is of interest to evaluate how the quantitative measures of lung density compare between dual-source and single-source scan modes. This study has sought to characterize in-vivo and phantom-based air metrics using dual-energy computed tomography technology where the nature of the technology has required adjustments to scatter correction. Anesthetized ovine (N=6), swine (N=13: more human-like rib cage shape), lung phantom and a thoracic phantom were studied using a dual-source MDCT scanner (Siemens Definition Flash. Multiple dual-source dual-energy (DSDE) and single-source (SS) scans taken at different energy levels and scan settings were acquired for direct quantitative comparison. Density histograms were evaluated for the lung, tracheal, water and blood segments. Image data were obtained at 80, 100, 120, and 140 kVp in the SS mode (B35f kernel) and at 80, 100, 140, and 140-Sn (tin filtered) kVp in the DSDE mode (B35f and D30f kernels), in addition to variations in dose, rotation time, and pitch. To minimize the effect of cross-scatter, the phantom scans in the DSDE mode was obtained by reducing the tube current of one of the tubes to its minimum (near zero) value. When using image data obtained in the DSDE mode, the median HU values in the tracheal regions of all animals and the phantom were consistently closer to -1000 HU regardless of reconstruction kernel (chapters 3 and 4). Similarly, HU values of water and blood were consistently closer to their nominal values of 0 HU and 55 HU respectively. When using image data obtained in the SS mode the air CT numbers demonstrated a consistent positive shift of up to 35 HU with respect to the nominal -1000 HU value. In vivo data demonstrated considerable variability in tracheal, influenced by local anatomy with SS mode scanning while tracheal air was more consistent with DSDE imaging. Scatter effects in the lung parenchyma differed from adjacent tracheal measures. In summary, data suggest that enhanced scatter correction serves to provide more accurate CT lung density measures sought to quantitatively assess the presence and distribution of emphysema in COPD subjects. Data further suggest that CT images, acquired without adequate scatter correction, cannot be corrected by linear algorithms given the variability in tracheal air HU values and the independent scatter effects on lung parenchyma.

Non-destructive X-ray Computed Tomography (XCT) Analysis of Sediment Variance in Marine Cores

NASA Astrophysics Data System (ADS)

Oti, E.; Polyak, L. V.; Dipre, G.; Sawyer, D.; Cook, A.

2015-12-01

Benthic activity within marine sediments can alter the physical properties of the sediment as well as indicate nutrient flux and ocean temperatures. We examine burrowing features in sediment cores from the western Arctic Ocean collected during the 2005 Healy-Oden TransArctic Expedition (HOTRAX) and from the Gulf of Mexico Integrated Ocean Drilling Program (IODP) Expedition 308. While traditional methods for studying bioturbation require physical dissection of the cores, we assess burrowing using an X-ray computed tomography (XCT) scanner. XCT noninvasively images the sediment cores in three dimensions and produces density sensitive images suitable for quantitative analysis. XCT units are recorded as Hounsfield Units (HU), where -999 is air, 0 is water, and 4000-5000 would be a higher density mineral, such as pyrite. We rely on the fundamental assumption that sediments are deposited horizontally, and we analyze the variance over each flat-lying slice. The variance describes the spread of pixel values over a slice. When sediments are reworked, drawing higher and lower density matrix into a layer, the variance increases. Examples of this can be seen in two slices in core 19H-3A from Site U1324 of IODP Expedition 308. The first slice, located 165.6 meters below sea floor consists of relatively undisturbed sediment. Because of this, the majority of the sediment values fall between 1406 and 1497 HU, thus giving the slice a comparatively small variance of 819.7. The second slice, located 166.1 meters below sea floor, features a lower density sediment matrix disturbed by burrow tubes and the inclusion of a high density mineral. As a result, the Hounsfield Units have a larger variance of 1,197.5, which is a result of sediment matrix values that range from 1220 to 1260 HU, the high-density mineral value of 1920 HU and the burrow tubes that range from 1300 to 1410 HU. Analyzing this variance allows us to observe changes in the sediment matrix and more specifically capture where, and to what extent, the burrow tubes deviate from the sediment matrix. Future research will correlate changes in variance due to bioturbation to other features indicating ocean temperatures and nutrient flux, such as foraminifera counts and oxygen isotope data.

Computerized tomography attenuation values can be used to differentiate hydronephrosis from pyonephrosis.

PubMed

Yuruk, Emrah; Tuken, Murat; Sulejman, Suhejb; Colakerol, Aykut; Serefoglu, Ege Can; Sarica, Kemal; Muslumanoglu, Ahmet Yaser

2017-03-01

To determine the diagnostic value of computerized tomography (CT) in differentiating pyonephrosis from hydronephrosis on the basis of attenuation values (Hounsfield unit-HU). Data of the patients with grades 1-3 hydronephrosis on abdominopelvic CT, who underwent nephrostomy tube placement for decompression of the collecting system, were retrospectively analyzed. Patient demographics and CT findings were recorded along with the first access urine culture results. Three physicians calculated the surface areas and the attenuation values of the dilated collecting systems using the system software. Mean HU of pyonephrosis and hydronephrosis cases was compared. A total of 105 patients with the mean age of 47.7 ± 15.5 (range 20-80) were included. The interclass correlation coefficient of three physicians was 0.981 for HU measurement and 0.999 for calculation of collecting system surface area. Of the patients, 47 (44.8 %) had pyonephrosis. Mean surface areas of the collecting system were similar in patients with pyonephrosis and hydronephrosis (1481.13 ± 1562.94 vs. 1612.94 ± 2261.4 mm 2 , p = 0.735). Urine cultures were positive in all patients with pyonephrosis, whereas 12.7 % of hydronephrosis cases had bacterial in first access urine culture. The HU of the patients with pyonephrosis was significantly higher that that of patients with hydronephrosis (13.51 ± 13.29 vs. 4.67 ± 5.37, p = 0.0001). Having a HU of 9.21 or over diagnosed pyonephrosis accurately with 65.96 % sensitivity and 87.93 % specificity. Measuring attenuation values of the collecting system may be useful to differentiate pyonephrosis from hydronephrosis. Diagnosing pyonephrosis accurately may avoid septic complications.

Sensitivity of Hyperdense Basilar Artery Sign on Non-Enhanced Computed Tomography

PubMed Central

Ernst, Marielle; Romero, Javier M.; Buhk, Jan-Hendrik; Cheng, Bastian; Herrmann, Jochen; Fiehler, Jens; Groth, Michael

2015-01-01

Purpose The hyperdense basilar artery sign (HBAS) is an indicator of vessel occlusion on non contrast-enhanced computer tomography (NECT) in acute stroke patients. Since basilar artery occlusion (BAO) is associated with a high mortality and morbidity, its early detection is of great clinical value. We sought to analyze the influence of density measurement as well as a normalized ratio of Hounsfield unit/hematocrit (HU/Hct) ratio on the detection of BAO on NECT in patients with suspected BAO. Materials and Methods 102 patients with clinically suspected BAO were examined with NECT followed immediately by Multidetector computed tomography Angiography. Two observers independently analyzed the images regarding the presence or absence of HBAS on NECT and performed HU measurements in the basilar artery. Receiver operating characteristic curve analysis was performed to determine the optimal density threshold for BAO using attenuation measurements or HU/Hct ratio. Results Sensitivity of visual detection of the HBAS on NECT was relatively low 81% (95%-CI, 54–95%) while specificity was high 91% (95%-CI, 82–96%). The highest sensitivity was achieved by the combination of visual assessment and additional quantitative attenuation measurements applying a cut-off value of 46.5 HU with 94% sensitivity and 81% specificity for BAO. A HU/Hct ratio >1.32 revealed sensitivity of 88% (95%-CI, 60–98%) and specificity of 84% (95%-CI, 74–90%). Conclusion In patients with clinically suspected acute BAO the combination of visual assessment and additional attenuation measurement with a cut-off value of 46.5 HU is a reliable approach with high sensitivity in the detection of BAO on NECT. PMID:26479718

High-Density Free Fluid on Computed Tomography: a Predictor of Surgical Intervention in Patients with Adhesive Small Bowel Obstruction.

PubMed

Matsushima, Kazuhide; Inaba, Kenji; Dollbaum, Ryan; Cheng, Vincent; Khan, Moazzam; Herr, Keith; Strumwasser, Aaron; Asturias, Sabrina; Dilektasli, Evren; Demetriades, Demetrios

2016-11-01

Patients with adhesive small bowel obstruction (ASBO) often develop intraabdominal free fluid (IFF). While IFF is a finding on abdominopelvic computed tomography (CT) associated with the need for surgical intervention, many patients with IFF can be still managed non-operatively. A previous study suggested that a higher red blood cell count of IFF is highly predictive of strangulated ASBO. We hypothesized that radiodensity in IFF (Hounsfield unit (HU)) on CT would predict the need for surgical intervention. Patients with clinicoradiological evidence of ASBO between January 2009 and December 2013 were identified. In patients with IFF > 3 cm 2 identified on CT, the HU was measured in the largest pocket of IFF. A sensitivity analysis was performed to determine a high-density HU threshold. The HU of patients who underwent therapeutic laparotomy was compared with those successfully discharged with non-operative management. A total of 318 patients with ASBO (median age 52 years, 56.0 % male) were identified. Of 111 patients who had IFF on CT, 55.9 % underwent therapeutic laparotomy and 15.3 % required bowel resection. Radiodensity of IFF in the operative group was significantly higher than that in the non-operative group (18.2 vs. 7.0 HU, p < 0.01). Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of high-density IFF (>10 HU) to predict the need for surgical intervention were 83.9, 65.3, 75.4, 76.2, and 75.6 %, respectively. High-density IFF on CT was significantly associated with the need for surgical intervention in patients with ASBO. Prospective study to validate the predictive value of high-density IFF on CT will be warranted.

Hounsfield unit of screw trajectory as a predictor of pedicle screw loosening after single level lumber interbody fusion.

PubMed

Sakai, Yusuke; Takenaka, Shota; Matsuo, Yohei; Fujiwara, Hiroyasu; Honda, Hirotsugu; Makino, Takahiro; Kaito, Takashi

2018-06-01

This study aims to clarify the clinical potential of Hounsfield unit (HU), measured on computed tomography (CT) images, as a predictor of pedicle screw (PS) loosening, compared to bone mineral density (BMD). A total of 206 screws in 52 patients (21 men and 31 women; mean age 68.2 years) were analyzed retrospectively. The screws were classified into two groups depending on their screw loosening status on 3-month follow-up CT (loosening screw group vs. non-loosening screw group). Preoperative HU of the trajectory was evaluated by superimposing preoperative and postoperative CT images using three-dimensional image analysis software. Age, sex, body mass index, screw size, BMD of lumbar, and HU of screw trajectory were analyzed in association with screw loosening. Multivariate logistic regression analysis was performed, and the thresholds for PS loosening risk factors were evaluated using a continuous numerical variable and receiver operating characteristic (ROC) curve analyses. The area under the curve (AUC) was used to determine the diagnostic performance, and values > 0.75 were considered to represent good performance. The loosening screw group contained 24 screws (12%). Multivariate analysis revealed that the significant independent risk factors were not BMD but male sex [P = 0.028; odds ratio (OR) 2.852, 95% confidence interval (CI) 1.120-7.258] and HU of screw trajectory (P = 0.006; OR 0.989, 95% CI 0.980-0.997). ROC curve analysis demonstrated that the AUC for HU of screw trajectory for women was 0.880 (95% CI 0.798-0.961). The cutoff value was 153.5. AUC for men was 0.635 (95% CI 0.449-0.821), which was not considered to be a good performance. Low HU of screw trajectories was identified as a risk factor of PS loosening for women. For female patients with low HU, additional augmentation is recommended to prevent PS loosening. Copyright © 2018 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.

Dosimetric effects of endorectal balloons on intensity-modulated radiation therapy plans for prostate cancer

NASA Astrophysics Data System (ADS)

Kim, Jae-Sung; Chung, Jin-Beom; Kim, In-Ah; Eom, Keun-Yong

2013-10-01

We used an endorectal balloon (ERB) for prostate immobilization during intensity-modulated radiotherapy (IMRT) for prostate cancer treatment. To investigate the dosimetric effects of ERB-filling materials, we changed the ERB Hounsfield unit (HU) from 0 to 1000 HU in 200-HU intervals to simulate the various ERB fillings; 0 HU simulated a water-filled ERB, and 1000 HU simulated the densest material-filled ERB. Dosimetric data (coverage, homogeneity, conformity, maximal dose, and typical volume dose) for the tumor and the organs at risk (OARs) were evaluated in prostate IMRT treatment plans with 6-MV and 15-MV beams. The tumor coverage appeared to differ by approximately 1%, except for the clinical target volume (CTV) V100% and the planning target volume (PTV) V100%. The largest difference for the various ERB fillings was observed in the PTV V100%. In spite of increasing HU, the prostate IMRT plans at both energies had relatively low dosimetric effects on the PTV and the CTV. However, the maximal and the typical volume doses (D25%, D30%, and D50%) to the rectal wall and the bladder increased with increasing HU. For an air-filled ERB, the maximal doses to the rectal wall and the monitor units were lower than the corresponding values for the water-filled and the densest material-filled ERBs. An air-filled ERB spared the rectal wall because of its dosimetric effect. Thus, we conclude that the use of an air-filled ERB provides a dosimetric benefit to the rectal wall without a loss of target coverage and is an effective option for prostate IMRT treatment.

Study of Variation in Dose Calculation Accuracy Between kV Cone-Beam Computed Tomography and kV fan-Beam Computed Tomography

PubMed Central

Kaliyaperumal, Venkatesan; Raphael, C. Jomon; Varghese, K. Mathew; Gopu, Paul; Sivakumar, S.; Boban, Minu; Raj, N. Arunai Nambi; Senthilnathan, K.; Babu, P. Ramesh

2017-01-01

Cone-beam computed tomography (CBCT) images are presently used for geometric verification for daily patient positioning. In this work, we have compared the images of CBCT with the images of conventional fan beam CT (FBCT) in terms of image quality and Hounsfield units (HUs). We also compared the dose calculated using CBCT with that of FBCT. Homogenous RW3 plates and Catphan phantom were scanned by FBCT and CBCT. In RW3 and Catphan phantom, percentage depth dose (PDD), profiles, isodose distributions (for intensity modulated radiotherapy plans), and calculated dose volume histograms were compared. The HU difference was within ± 20 HU (central region) and ± 30 HU (peripheral region) for homogeneous RW3 plates. In the Catphan phantom, the difference in HU was ± 20 HU in the central area and peripheral areas. The HU differences were within ± 30 HU for all HU ranges starting from −1000 to 990 in phantom and patient images. In treatment plans done with simple symmetric and asymmetric fields, dose difference (DD) between CBCT plan and FBCT plan was within 1.2% for both phantoms. In intensity modulated radiotherapy (IMRT) treatment plans, for different target volumes, the difference was <2%. This feasibility study investigated HU variation and dose calculation accuracy between FBCT and CBCT based planning and has validated inverse planning algorithms with CBCT. In our study, we observed a larger deviation of HU values in the peripheral region compared to the central region. This is due to the ring artifact and scatter contribution which may prevent the use of CBCT as the primary imaging modality for radiotherapy treatment planning. The reconstruction algorithm needs to be modified further for improving the image quality and accuracy in HU values. However, our study with TG-119 and intensity modulated radiotherapy test targets shows that CBCT can be used for adaptive replanning as the recalculation of dose with the anisotropic analytical algorithm is in full accord with conventional planning CT except in the build-up regions. Patient images with CBCT have to be carefully analyzed for any artifacts before using them for such dose calculations. PMID:28974864

Antiplatelet Usage Impacts Clot Density in Acute Anterior Circulation Ischemic Stroke

PubMed Central

Pikija, Slaven; Magdic, Jozef; Lukic, Anita; Schreiber, Catharina; Mutzenbach, Johannes Sebastian; McCoy, Mark R.; Sellner, Johann

2016-01-01

We explored whether clot density in middle cerebral artery (MCA) occlusion is related to clinical variables, stroke etiology, blood constituents, and prestroke medication. We performed a retrospective chart review of patients with acute ischemic stroke of the anterior circulation admitted to two Central European stroke centers. The acquisition of non-contrast enhanced CT (NECT) and CT angiography (CTA) within 4.5 h of symptom onset was obligatory. We assessed the site of MCA occlusion as well as density, area, and length of the clot in 150 patients. The Hounsfield unit values for the clot were divided with contralateral MCA segment to yield relative Hounsfield Unit ratio (rHU). The site of the vessel occlusion (M1 vs. M2) and antiplatelet usage, but not stroke etiology, significantly influenced rHU. We found an inverse correlation of rHU with erythrocyte count (p < 0.001). The multivariate analysis revealed that a higher rHU (i.e., clot being more hyperdense) was more likely with the use of antiplatelets (OR 4.24, CI 1.10–16.31, p = 0.036). Erythrocyte (OR 0.18, CI 0.05–0.55, p = 0.003), and thrombocyte counts (OR 0.99, CI 0.98–0.99, p = 0.029) were associated with odds for more hypodense clots (lower rHU). Our study disclosed that antiplatelet therapy impacts the composition of intracranial clots of the anterior circulation. PMID:27563874

Hounsfield unit recovery in clinical cone beam CT images of the thorax acquired for image guided radiation therapy

NASA Astrophysics Data System (ADS)

Slot Thing, Rune; Bernchou, Uffe; Mainegra-Hing, Ernesto; Hansen, Olfred; Brink, Carsten

2016-08-01

A comprehensive artefact correction method for clinical cone beam CT (CBCT) images acquired for image guided radiation therapy (IGRT) on a commercial system is presented. The method is demonstrated to reduce artefacts and recover CT-like Hounsfield units (HU) in reconstructed CBCT images of five lung cancer patients. Projection image based artefact corrections of image lag, detector scatter, body scatter and beam hardening are described and applied to CBCT images of five lung cancer patients. Image quality is evaluated through visual appearance of the reconstructed images, HU-correspondence with the planning CT images, and total volume HU error. Artefacts are reduced and CT-like HUs are recovered in the artefact corrected CBCT images. Visual inspection confirms that artefacts are indeed suppressed by the proposed method, and the HU root mean square difference between reconstructed CBCTs and the reference CT images are reduced by 31% when using the artefact corrections compared to the standard clinical CBCT reconstruction. A versatile artefact correction method for clinical CBCT images acquired for IGRT has been developed. HU values are recovered in the corrected CBCT images. The proposed method relies on post processing of clinical projection images, and does not require patient specific optimisation. It is thus a powerful tool for image quality improvement of large numbers of CBCT images.

Analysis of intensity variability in multislice and cone beam computed tomography.

PubMed

Nackaerts, Olivia; Maes, Frederik; Yan, Hua; Couto Souza, Paulo; Pauwels, Ruben; Jacobs, Reinhilde

2011-08-01

The aim of this study was to evaluate the variability of intensity values in cone beam computed tomography (CBCT) imaging compared with multislice computed tomography Hounsfield units (MSCT HU) in order to assess the reliability of density assessments using CBCT images. A quality control phantom was scanned with an MSCT scanner and five CBCT scanners. In one CBCT scanner, the phantom was scanned repeatedly in the same and in different positions. Images were analyzed using registration to a mathematical model. MSCT images were used as a reference. Density profiles of MSCT showed stable HU values, whereas in CBCT imaging the intensity values were variable over the profile. Repositioning of the phantom resulted in large fluctuations in intensity values. The use of intensity values in CBCT images is not reliable, because the values are influenced by device, imaging parameters and positioning. © 2011 John Wiley & Sons A/S.

Practical determination of aortic valve calcium volume score on contrast-enhanced computed tomography prior to transcatheter aortic valve replacement and impact on paravalvular regurgitation: Elucidating optimal threshold cutoffs.

PubMed

Bettinger, Nicolas; Khalique, Omar K; Krepp, Joseph M; Hamid, Nadira B; Bae, David J; Pulerwitz, Todd C; Liao, Ming; Hahn, Rebecca T; Vahl, Torsten P; Nazif, Tamim M; George, Isaac; Leon, Martin B; Einstein, Andrew J; Kodali, Susheel K

The threshold for the optimal computed tomography (CT) number in Hounsfield Units (HU) to quantify aortic valvular calcium on contrast-enhanced scans has not been standardized. Our aim was to find the most accurate threshold to predict paravalvular regurgitation (PVR) after transcatheter aortic valve replacement (TAVR). 104 patients who underwent TAVR with the CoreValve prosthesis were studied retrospectively. Luminal attenuation (LA) in HU was measured at the level of the aortic annulus. Calcium volume score for the aortic valvular complex was measured using 6 threshold cutoffs (650 HU, 850 HU, LA × 1.25, LA × 1.5, LA+50, LA+100). Receiver-operating characteristic (ROC) analysis was performed to assess the predictive value for > mild PVR (n = 16). Multivariable analysis was performed to determine the accuracy to predict > mild PVR after adjustment for depth and perimeter oversizing. ROC analysis showed lower area under the curve (AUC) values for fixed threshold cutoffs (650 or 850 HU) compared to thresholds relative to LA. The LA+100 threshold had the highest AUC (0.81), and AUC was higher than all studied protocols, other than the LA x 1.25 and LA + 50 protocols, where the difference approached statistical significance (p = 0.05, and 0.068, respectively). Multivariable analysis showed calcium volume determined by the LAx1.25, LAx1.5, LA+50, and LA+ 100 HU protocols to independently predict PVR. Calcium volume scoring thresholds which are relative to LA are more predictive of PVR post-TAVR than those which use fixed cutoffs. A threshold of LA+100 HU had the highest predictive value. Copyright © 2017 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.

Acoustic property reconstruction of a neonate Yangtze finless porpoise's (Neophocaena asiaeorientalis) head based on CT imaging.

PubMed

Wei, Chong; Wang, Zhitao; Song, Zhongchang; Wang, Kexiong; Wang, Ding; Au, Whitlow W L; Zhang, Yu

2015-01-01

The reconstruction of the acoustic properties of a neonate finless porpoise's head was performed using X-ray computed tomography (CT). The head of the deceased neonate porpoise was also segmented across the body axis and cut into slices. The averaged sound velocity and density were measured, and the Hounsfield units (HU) of the corresponding slices were obtained from computed tomography scanning. A regression analysis was employed to show the linear relationships between the Hounsfield unit and both sound velocity and density of samples. Furthermore, the CT imaging data were used to compare the HU value, sound velocity, density and acoustic characteristic impedance of the main tissues in the porpoise's head. The results showed that the linear relationships between HU and both sound velocity and density were qualitatively consistent with previous studies on Indo-pacific humpback dolphins and Cuvier's beaked whales. However, there was no significant increase of the sound velocity and acoustic impedance from the inner core to the outer layer in this neonate finless porpoise's melon.

Use of erythropoietin and its effects on blood lactate and 2, 3-diphosphoglycerate in premature neonates.

PubMed

Soubasi, V; Kremenopoulos, G; Tsantali, C; Savopoulou, P; Mussafiris, C; Dimitriou, M

2000-11-01

The aim of this study was to investigate the effect of recombinant human erythropoietin (rHu-EPO) on oxygen affinity and adequate oxygen delivery to the tissues of stable premature infants. 36 very-low-birth-weight infants were randomly assigned to either receive rHu-EPO (200 units/kg every other day) or not, and both groups were supplemented with iron, folic acid and vitamin E. Arterial blood gases, oxygen saturation, complete blood counts, fetal haemoglobin, 2,3-diphosphoglycerate (2,3-DPG) and blood lactate were analysed weekly, from the 1st week till discharge. Patients in the two groups were comparable. There was a trend in increasing lactate values towards the 4th to 5th weeks of life, which did not reach statistical significance. There was no correlation between lactate values and the studied variables (pH, BE, oxygen saturation). In 35 transfusions, pre- and 24 h post-transfusion blood lactate status was studied. In 23 of them, a decrease in post-transfusion lactate was noticed, whilst an increased post-transfusion level was shown in 10 cases and no change in 2 cases. The mean pre-transfusion lactate value was significantly higher than the post-transfusion one (24.04 +/- 11.9 mg/dl before and 16.27 +/- 8.5 mg/dl after transfusion; p = 0.0025). In both groups there was a steady rise in 2,3-DPG concentration over the period of study, and the 2,3-DPG values at the end of our study were significantly increased in the rHu-EPO group (rHu-EPO 5.98 +/- 0.9, control 4.84 +/- 0.7; p = 0.04). In conclusion, the use of rHu-EPO did not affect blood lactate levels compared to the control group. Regarding oxygen affinity, it seems that rHu-EPO causes a shift of the oxy-haemoglobin dissociation curve to the right. This is a previously unreported effect of rHu-EPO and its clinical use may, thus, confer to preterm babies an added advantage.

Effect of Hemoconcentration on Dural Sinus Computed Tomography Density in a Pediatric Population.

PubMed

Yurttutan, Nursel; Kizildag, Betul; Sarica, Mehmet Akif; Baykara, Murat

2016-10-01

Unenhanced brain computed tomography (CT) is inexpensive, easily available, and the first-choice imaging modality for patients presenting with various neurologic symptoms. Venous thrombosis is not rare in childhood, but diagnosis can be difficult. In some cases, only denser vessels can be used to highlight an issue. The aim of this study was to retrospectively evaluate the relationship between X-ray attenuation and hemoconcentration in a pediatric population. This study enrolled 99 pediatric patients who had been referred radiology department for unenhanced brain CT. Images were retrospectively evaluated for measurement of dural sinus densities from four distinct dural sinus locations. Correlation between mean Hounsfield unit (HU) values and hemoglobin/hematocrit (Hb/Htc) levels, as well as age and gender were further analyzed. There was a strong correlation between mean HU and Hb levels (r = 0.411; standard deviation: 0.001) and also between mean HU and Htc levels (r = 0.393; p < 0.001). According to the results of this study, the mean sinus density and H:H (HU:Htc) values were 44.06 HU and 1.19, respectively, in a normal pediatric group. In conclusion, before deciding between a diagnosis of thrombosis and a determination of normal findings during an evaluation of unenhanced CT in a pediatric population, radiologists should consider complete blood count results as well as H:H ratios. Georg Thieme Verlag KG Stuttgart · New York.

Baseline Tumor Lipiodol Uptake after Transarterial Chemoembolization for Hepatocellular Carcinoma: Identification of a Threshold Value Predicting Tumor Recurrence.

PubMed

Matsui, Yusuke; Horikawa, Masahiro; Jahangiri Noudeh, Younes; Kaufman, John A; Kolbeck, Kenneth J; Farsad, Khashayar

2017-12-01

The aim of the study was to evaluate the association between baseline Lipiodol uptake in hepatocellular carcinoma (HCC) after transarterial chemoembolization (TACE) with early tumor recurrence, and to identify a threshold baseline uptake value predicting tumor response. A single-institution retrospective database of HCC treated with Lipiodol-TACE was reviewed. Forty-six tumors in 30 patients treated with a Lipiodol-chemotherapy emulsion and no additional particle embolization were included. Baseline Lipiodol uptake was measured as the mean Hounsfield units (HU) on a CT within one week after TACE. Washout rate was calculated dividing the difference in HU between the baseline CT and follow-up CT by time (HU/month). Cox proportional hazard models were used to correlate baseline Lipiodol uptake and other variables with tumor response. A receiver operating characteristic (ROC) curve was used to identify the optimal threshold for baseline Lipiodol uptake predicting tumor response. During the follow-up period (mean 5.6 months), 19 (41.3%) tumors recurred (mean time to recurrence = 3.6 months). In a multivariate model, low baseline Lipiodol uptake and higher washout rate were significant predictors of early tumor recurrence ( P = 0.001 and < 0.0001, respectively). On ROC analysis, a threshold Lipiodol uptake of 270.2 HU was significantly associated with tumor response (95% sensitivity, 93% specificity). Baseline Lipiodol uptake and washout rate on follow-up were independent predictors of early tumor recurrence. A threshold value of baseline Lipiodol uptake > 270.2 HU was highly sensitive and specific for tumor response. These findings may prove useful for determining subsequent treatment strategies after Lipiodol TACE.

Adrenal glands in hypovolemic shock: preservation of contrast enhancement at dynamic computed tomography.

PubMed

Ito, Katsuyoshi; Higashi, Hiroki; Kanki, Akihiko; Tamada, Tsutomu; Yamashita, Takenori; Yamamoto, Akira; Watanabe, Shigeru

2010-07-01

To evaluate contrast enhancement effects of the adrenal glands at dynamic computed tomography (CT) in adult severe trauma patients with hypovolemic shock in comparison with patients without hypovolemic shock. This study population included a total of 74 patients with (n = 24) and without (n = 50) blunt trauma and hypovolemic shock. Measurement of CT attenuation values of the adrenal gland and calculation of the enhancement washout percentages were performed. The mean +/- SD CT attenuation values of the adrenal glands in the arterial phase of dynamic CT in patients with hypovolemic shock (137.3 +/- 41.7 Hounsfield unit [HU]) were not significantly different (P = 0.16) from those in control subjects (127.3 +/- 19.6 HU). The mean CT attenuation values of the adrenal glands in the delayed phase of dynamic CT in patients with hypovolemic shock (82.0 +/- 14.7 HU) were also not significantly different (P = 0.89) from those in control subjects (82.4 +/- 10.0 HU). The mean percentage (35%) of enhancement washout of the adrenal glands in patients with hypovolemic shock was not significantly different (P = 0.81) from that (34%) in control subjects. Contrast enhancement effects of the adrenal glands at contrast-enhanced dynamic CT in patients with hypovolemic shock were similar to those in control subjects, indicating the preserved enhancement and perfusion of the adrenal gland rather than intense and persistent enhancement in patients with hypovolemic shock.

SU-F-T-220: Validation of Hounsfield Unit-To-Stopping Power Ratio Calibration Used for Dose Calculation in Proton Radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Polf, J; Chung, H; Langen, K

Purpose: To validate the stoichiometric calibration of the Hounsfield Unit (HU) to Stopping Power Ratio (SPR) calibration used to commission a commercial treatment planning system (TPS) for proton radiotherapy dose calculation. Methods and Materials: The water equivalent thickness (WET) of several individual pig tissues (lung, fat, muscle, liver, intestine, rib, femur), mixed tissue samples (muscle/rib, ice/femur, rib/air cavity/muscle), and an intact pig head were measured with a multi-layer ionization chamber (MLIC). A CT scan of each sample was obtained and imported into a commercial TPS. The WET calculated by the TPS for each tissue sample was compared to the measuredmore » WET value to determine the accuracy of the HU-to-SPR calibration curve used by the TPS to calculate dose. Results: The WET values calculated by the TPS showed good agreement (< 2.0%) with the measured values for bone and all soft tissues except fat (3.1% difference). For the mixed tissue samples and the intact pig head measurements, the difference in the TPS and measured WET values all agreed to within 3.5%. In addition, SPR values were calculated from the measured WET of each tissue, and compared to SPR values of reference tissues from ICRU 46 used to generate the HU-to-SPR calibration for the TPS. Conclusion: For clinical scenarios where the beam passes through multiple tissue types and its path is dominated by soft tissues, we believe using an uncertainty of 3.5% of the planned beam range is acceptable to account for uncertainties in the TPS WET determination.« less

Can a dual-energy computed tomography predict unsuitable stone components for extracorporeal shock wave lithotripsy?

PubMed

Ahn, Sung Hoon; Oh, Tae Hoon; Seo, Ill Young

2015-09-01

To assess the potential of dual-energy computed tomography (DECT) to identify urinary stone components, particularly uric acid and calcium oxalate monohydrate, which are unsuitable for extracorporeal shock wave lithotripsy (ESWL). This clinical study included 246 patients who underwent removal of urinary stones and an analysis of stone components between November 2009 and August 2013. All patients received preoperative DECT using two energy values (80 kVp and 140 kVp). Hounsfield units (HU) were measured and matched to the stone component. Significant differences in HU values were observed between uric acid and nonuric acid stones at the 80 and 140 kVp energy values (p<0.001). All uric acid stones were red on color-coded DECT images, whereas 96.3% of the nonuric acid stones were blue. Patients with calcium oxalate stones were divided into two groups according to the amount of monohydrate (calcium oxalate monohydrate group: monohydrate≥90%, calcium oxalate dihydrate group: monohydrate<90%). Significant differences in HU values were detected between the two groups at both energy values (p<0.001). DECT improved the characterization of urinary stone components and was a useful method for identifying uric acid and calcium oxalate monohydrate stones, which are unsuitable for ESWL.

Bronchocele density in cystic fibrosis as an indicator of allergic broncho-pulmonary aspergillosis: A preliminary study.

PubMed

Occelli, Aurélie; Soize, Sébastien; Ranc, Caroline; Giovannini-Chami, Lisa; Bailly, Carole; Leloutre, Béatrice; Boyer, Corinne; Baque-Juston, Marie

2017-08-01

Allergic broncho-pulmonary aspergillosis (ABPA) is a severe and under-diagnosed complication of cystic fibrosis (CF). The aim of the study was to determine whether the mucus content of bronchoceles in cystic fibrosis complicated with ABPA reveals a higher density than the mucus content of non-ABPA cystic fibrosis. We studied retrospectively 43 computed tomography scans (CT scans) of a pediatric population of cystic fibrosis patients. We measured the mucus attenuation in Hounsfield Units (HU) of all bronchoceles >5mm in diameter. We found bronchoceles >5mm in 13/43 patients. 5/13 patients had a positive diagnosis of ABPA. The median HU value of bronchoceles was higher in patients with than without ABPA [98 HU (26-135) vs 28 HU (10-36); P=0,02]. Moreover, all patients with a bronchocele density >36HU were ABPA positive. CF complicated with ABPA shows higher attenuation bronchoceles on CT scans of the chest. Systematic density measurements of bronchoceles could help to raise the difficult diagnosis of ABPA in patients suffering from cystic fibrosis. Larger series could confirm a threshold in HU which could become a new imaging criterion for the diagnosis of ABPA. Copyright © 2017 Elsevier B.V. All rights reserved.

Identification of infusion strategy for achieving repeatable nanoparticle distribution and quantification of thermal dosage using micro-CT Hounsfield unit in magnetic nanoparticle hyperthermia.

PubMed

LeBrun, Alexander; Joglekar, Tejashree; Bieberich, Charles; Ma, Ronghui; Zhu, Liang

2016-01-01

The objective of this study was to identify an injection strategy leading to repeatable nanoparticle deposition patterns in tumours and to quantify volumetric heat generation rate distribution based on micro-CT Hounsfield unit (HU) in magnetic nanoparticle hyperthermia. In vivo animal experiments were performed on graft prostatic cancer (PC3) tumours in immunodeficient mice to investigate whether lowering ferrofluid infusion rate improves control of the distribution of magnetic nanoparticles in tumour tissue. Nanoparticle distribution volume obtained from micro-CT scan was used to evaluate spreading of the nanoparticles from the injection site in tumours. Heating experiments were performed to quantify relationships among micro-CT HU values, local nanoparticle concentrations in the tumours, and the ferrofluid-induced volumetric heat generation rate (q(MNH)) when nanoparticles were subject to an alternating magnetic field. An infusion rate of 3 µL/min was identified to result in the most repeatable nanoparticle distribution in PC3 tumours. Linear relationships have been obtained to first convert micro-CT greyscale values to HU values, then to local nanoparticle concentrations, and finally to nanoparticle-induced q(MNH) values. The total energy deposition rate in tumours was calculated and the observed similarity in total energy deposition rates in all three infusion rate groups suggests improvement in minimising nanoparticle leakage from the tumours. The results of this study demonstrate that micro-CT generated q(MNH) distribution and tumour physical models improve predicting capability of heat transfer simulation for designing reliable treatment protocols using magnetic nanoparticle hyperthermia.

Development of a Multileaf Collimator for Proton Therapy

DTIC Science & Technology

2012-11-01

Hounsfield Units (HU) into density bins (of width 10 kg/m^3), we now define a unique density for each Hounsfield Unit . The density resolution is thus...patient basis given some knowledge about any implants they might have. 24 The calibration of CT Hounsfield unit to material type and density was...that region, resulting in a hot ring around the cold spot. It was determined that the Hounsfield unit values corresponding to the voxels in the cold

SU-E-T-599: The Variation of Hounsfield Unit and Relative Electron Density Determination as a Function of KVp and Its Effect On Dose Calculation Accuracy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ohl, A; Boer, S De

Purpose: To investigate the differences in relative electron density for different energy (kVp) settings and the effect that these differences have on dose calculations. Methods: A Nuclear Associates 76-430 Mini CT QC Phantom with materials of known relative electron densities was imaged by one multi-slice (16) and one single-slice computed tomography (CT) scanner. The Hounsfield unit (HU) was recorded for each material with energies ranging from 80 to 140 kVp and a representative relative electron density (RED) curve was created. A 5 cm thick inhomogeneity was created in the treatment planning system (TPS) image at a depth of 5 cm.more » The inhomogeneity was assigned HU for various materials for each kVp calibration curve. The dose was then calculated with the analytical anisotropic algorithm (AAA) at points within and below the inhomogeneity and compared using the 80 kVp beam as a baseline. Results: The differences in RED values as a function of kVp showed the largest variations of 580 and 547 HU for the Aluminum and Bone materials; the smallest differences of 0.6 and 3.0 HU were observed for the air and lung inhomogeneities. The corresponding dose calculations for the different RED values assigned to the 5 cm thick slab revealed the largest differences inside the aluminum and bone inhomogeneities of 2.2 to 6.4% and 4.3 to 7.0% respectively. The dose differences beyond these two inhomogeneities were between 0.4 to 1.6% for aluminum and 1.9 to 2.2 % for bone. For materials with lower HU the calculated dose differences were less than 1.0%. Conclusion: For high CT number materials the dose differences in the phantom calculation as high as 7.0% are significant. This result may indicate that implementing energy specific RED curves can increase dose calculation accuracy.« less

SU-E-T-161: Characterization and Validation of CT Simulator Hounsfield Units to Relative Stopping Power Values for Proton Treatment Planning

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schnell, E; Ahmad, S; De La Fuente Herman, T

2015-06-15

Purpose: To develop a calibration curve that includes and minimizes the variations of Hounsfield Unit (HU) from a CT scanner to Relative Stopping Power (RSP) of tissues along the proton beam path. The variations are due to scanner and proton energy, technique, phantom size and placement, and tissue arrangement. Methods: A CIRS 062 M phantom with 10 plugs of known relative electron density (RED) was scanned through a 16 slice GE Discovery CT Simulator scanner. Three setup combinations of plug distributions and techniques clinically implemented for five treatment regions were scanned with energies of 100, 120, and 140 kV. Volumetricmore » HU values were measured for each plug and scan. The RSP values derived through the Bethe-Bloch formula are currently being verified with parallel-plate ionization chamber measurements in water using 80, 150, and 225 MeV proton beam. Typical treatment plans for treatment regions of brain, head-&-neck, chest, abdomen, and pelvis are being planned and dose delivered will be compared with film and Optically Stimulated Luminescence (OSL) measurements. Results: Percentage variations were determined for each variable. For tissues close to water, variations were <1% from any given parameter. Tissues far from water equivalence (lung and bone) showed the greatest sensitivity to change (7.4% maximum) with scanner energy and up to 5.3% with positioning of the phantom. No major variations were observed for proton energies within the treatment range. Conclusion: When deriving a calibration curve, attention should be placed to low and high HU values. A thorough verification process of calculated vs. water-phantom measured RSP values at different proton energies, followed by dose validation of planned vs. measured doses in phantom with film and OSL detectors are currently being undertaken.« less

SU-E-QI-16: Reproducibility of Computed Tomography Quantitative Structural Features Using the FDA Thoracic Phantom Image Database

DOE Office of Scientific and Technical Information (OSTI.GOV)

Budzevich, M; Grove, O; Balagurunathan, Y

Purpose: To assess the reproducibility of quantitative structural features using images from the computed tomography thoracic FDA phantom database under different scanning conditions. Methods: Development of quantitative image features to describe lesion shape and size, beyond conventional RECIST measures, is an evolving area of research in need of benchmarking standards. Gavrielides et al. (2010) scanned a FDA-developed thoracic phantom with nodules of various Hounsfield units (HU) values, shapes and sizes close to vascular structures using several scanners and varying scanning conditions/parameters; these images are in the public domain. We tested six structural features, namely, Convexity, Perimeter, Major Axis, Minor Axis,more » Extent Mean and Eccentricity, to characterize lung nodules. Convexity measures lesion irregularity referenced to a convex surface. Previously, we showed it to have prognostic value in lung adenocarcinoma. The above metrics and RECIST measures were evaluated on three spiculated (8mm/-300HU, 12mm/+30HU and 15mm/+30HU) and two non-spiculated (8mm/+100HU and 10mm/+100HU) nodules (from layout 2) imaged at three different mAs values: 25, 100 and 200 mAs; on a Phillips scanner (16-slice Mx8000-IDT; 3mm slice thickness). The nodules were segmented semi-automatically using a commercial software tool; the same HU range was used for all nodules. Results: Analysis showed convexity having the lowest maximum coefficient of variation (MCV): 1.1% and 0.6% for spiculated and non-spiculated nodules, respectively, much lower compared to RECIST Major and Minor axes whose MCV were 10.1% and 13.4% for spiculated, and 1.9% and 2.3% for non-spiculated nodules, respectively, across the various mAs. MCVs were consistently larger for speculated nodules. In general, the dependence of structural features on mAs (noise) was low. Conclusion: The FDA phantom CT database may be used for benchmarking of structural features for various scanners and scanning conditions; we used only a small fraction of available data. Our feature convexity outperformed other structural features including RECIST measures.« less

Is Preoperative Biochemical Testing for Pheochromocytoma Necessary for All Adrenal Incidentalomas?

PubMed Central

Jun, Joo Hyun; Ahn, Hyun Joo; Lee, Sangmin M.; Kim, Jie Ae; Park, Byung Kwan; Kim, Jee Soo; Kim, Jung Han

2015-01-01

Abstract This study examined whether imaging phenotypes obtained from computed tomography (CT) can replace biochemical tests to exclude pheochromocytoma among adrenal incidentalomas (AIs) in the preoperative setting. We retrospectively reviewed the medical records of all patients (n = 251) who were admitted for operations and underwent adrenal-protocol CT for an incidentally discovered adrenal mass from January 2011 to December 2012. Various imaging phenotypes were assessed for their screening power for pheochromocytoma. Final diagnosis was confirmed by biopsy, biochemical tests, and follow-up CT. Pheochromocytomas showed similar imaging phenotypes as malignancies, but were significantly different from adenomas. Unenhanced attenuation values ≤10 Hounsfield units (HU) showed the highest specificity (97%) for excluding pheochromocytoma as a single phenotype. A combination of size ≤3 cm, unenhanced attenuation values ≤ 10 HU, and absence of suspicious morphology showed 100% specificity for excluding pheochromocytoma. Routine noncontrast CT can be used as a screening tool for pheochromocytoma by combining 3 imaging phenotypes: size ≤3 cm, unenhanced attenuation values ≤10 HU, and absence of suspicious morphology, and may substitute for biochemical testing in the preoperative setting. PMID:26559265

4D-CT Lung registration using anatomy-based multi-level multi-resolution optical flow analysis and thin-plate splines.

PubMed

Min, Yugang; Neylon, John; Shah, Amish; Meeks, Sanford; Lee, Percy; Kupelian, Patrick; Santhanam, Anand P

2014-09-01

The accuracy of 4D-CT registration is limited by inconsistent Hounsfield unit (HU) values in the 4D-CT data from one respiratory phase to another and lower image contrast for lung substructures. This paper presents an optical flow and thin-plate spline (TPS)-based 4D-CT registration method to account for these limitations. The use of unified HU values on multiple anatomy levels (e.g., the lung contour, blood vessels, and parenchyma) accounts for registration errors by inconsistent landmark HU value. While 3D multi-resolution optical flow analysis registers each anatomical level, TPS is employed for propagating the results from one anatomical level to another ultimately leading to the 4D-CT registration. 4D-CT registration was validated using target registration error (TRE), inverse consistency error (ICE) metrics, and a statistical image comparison using Gamma criteria of 1 % intensity difference in 2 mm(3) window range. Validation results showed that the proposed method was able to register CT lung datasets with TRE and ICE values <3 mm. In addition, the average number of voxel that failed the Gamma criteria was <3 %, which supports the clinical applicability of the propose registration mechanism. The proposed 4D-CT registration computes the volumetric lung deformations within clinically viable accuracy.

Hounsfield Unit inaccuracy in computed tomography lesion size and density, diagnostic quality vs attenuation correction

NASA Astrophysics Data System (ADS)

Szczepura, Katy; Thompson, John; Manning, David

2017-03-01

In computed tomography the Hounsfield Units (HU) are used as an indicator of the tissue type based on the linear attenuation coefficients of the tissue. HU accuracy is essential when this metric is used in any form to support diagnosis. In hybrid imaging, such as SPECT/CT and PET/CT, the information is used for attenuation correction (AC) of the emission images. This work investigates the HU accuracy of nodules of known size and HU, comparing diagnostic quality (DQ) images with images used for AC.

Is scoring system of computed tomography based metric parameters can accurately predicts shock wave lithotripsy stone-free rates and aid in the development of treatment strategies?

PubMed Central

Badran, Yasser Ali; Abdelaziz, Alsayed Saad; Shehab, Mohamed Ahmed; Mohamed, Hazem Abdelsabour Dief; Emara, Absel-Aziz Ali; Elnabtity, Ali Mohamed Ali; Ghanem, Maged Mohammed; ELHelaly, Hesham Abdel Azim

2016-01-01

Objective: The objective was to determine the predicting success of shock wave lithotripsy (SWL) using a combination of computed tomography based metric parameters to improve the treatment plan. Patients and Methods: Consecutive 180 patients with symptomatic upper urinary tract calculi 20 mm or less were enrolled in our study underwent extracorporeal SWL were divided into two main groups, according to the stone size, Group A (92 patients with stone ≤10 mm) and Group B (88 patients with stone >10 mm). Both groups were evaluated, according to the skin to stone distance (SSD) and Hounsfield units (≤500, 500–1000 and >1000 HU). Results: Both groups were comparable in baseline data and stone characteristics. About 92.3% of Group A rendered stone-free, whereas 77.2% were stone-free in Group B (P = 0.001). Furthermore, in both group SWL success rates was a significantly higher for stones with lower attenuation <830 HU than with stones >830 HU (P < 0.034). SSD were statistically differences in SWL outcome (P < 0.02). Simultaneous consideration of three parameters stone size, stone attenuation value, and SSD; we found that stone-free rate (SFR) was 100% for stone attenuation value <830 HU for stone <10 mm or >10 mm but total number SWL sessions and shock waves required for the larger stone group were higher than in the smaller group (P < 0.01). Furthermore, SFR was 83.3% and 37.5% for stone <10 mm, mean HU >830, SSD 90 mm and SSD >120 mm, respectively. On the other hand, SFR was 52.6% and 28.57% for stone >10 mm, mean HU >830, SSD <90 mm and SSD >120 mm, respectively. Conclusion: Stone size, stone density (HU), and SSD is simple to calculate and can be reported by radiologists to applying combined score help to augment predictive power of SWL, reduce cost, and improving of treatment strategies. PMID:27141192

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, J; Zhang, W; Lu, J

Purpose: To investigate the accuracy and feasibility of dose calculations using kilovoltage cone beam computed tomography in cervical cancer radiotherapy using a correction algorithm. Methods: The Hounsfield units (HU) and electron density (HU-density) curve was obtained for both planning CT (pCT) and kilovoltage cone beam CT (CBCT) using a CIRS-062 calibration phantom. The pCT and kV-CBCT images have different HU values, and if the HU-density curve of CBCT was directly used to calculate dose in CBCT images may have a deviation on dose distribution. It is necessary to normalize the different HU values between pCT and CBCT. A HU correctionmore » algorithm was used for CBCT images (cCBCT). Fifteen intensity-modulated radiation therapy (IMRT) plans of cervical cancer were chosen, and the plans were transferred to the pCT and cCBCT data sets without any changes for dose calculations. Phantom and patient studies were carried out. The dose differences and dose distributions were compared between cCBCT plan and pCT plan. Results: The HU number of CBCT was measured by several times, and the maximum change was less than 2%. To compare with pCT, the CBCT and cCBCT has a discrepancy, the dose differences in CBCT and cCBCT images were 2.48%±0.65% (range: 1.3%∼3.8%) and 0.48%±0.21% (range: 0.1%∼0.82%) for phantom study, respectively. For dose calculation in patient images, the dose differences were 2.25%±0.43% (range: 1.4%∼3.4%) and 0.63%±0.35% (range: 0.13%∼0.97%), respectively. And for the dose distributions, the passing rate of cCBCT was higher than the CBCTs. Conclusion: The CBCT image for dose calculation is feasible in cervical cancer radiotherapy, and the correction algorithm offers acceptable accuracy. It will become a useful tool for adaptive radiation therapy.« less

USE OF COMPUTED TOMOGRAPHY FOR INVESTIGATION OF HEPATIC LIPIDOSIS IN CAPTIVE CHELONOIDIS CARBONARIA (SPIX, 1824).

PubMed

Marchiori, Adriano; da Silva, Ieverton Cleiton Correia; de Albuquerque Bonelli, Marília; de Albuquerque Zanotti, Luciana Carla Rameh; Siqueira, Daniel B; Zanotti, Alexandre Pinheiro; Costa, Fabiano Séllos

2015-06-01

Computed tomography is a sensitive and highly applicable technique for determining the degree of radiographic attenuation of the hepatic parenchyma. Radiodensity measurements of the liver can help in the diagnosis of hepatic lipidosis in humans and animals. The objective was to investigate the presence of hepatic lipidosis in captive red-footed tortoises (Chelonoidis carbonaria) using computed tomography. Computed tomography was performed in 10 male red-footed tortoises. Mean radiographic attenuation values for the hepatic parenchyma were 11.2±3.0 Hounsfield units (HU). Seven red-footed tortoises had values lower than 20 HU, which is compatible with C. carbonaria hepatic lipidosis. These results allowed an early diagnosis of the hepatic changes and suggested corrective measures regarding feeding and management protocols.

SU-F-J-175: Evaluation of Metal Artifact Reduction Algorithms in Computed Tomography and Their Application to Radiation Therapy Treatment Planning

DOE Office of Scientific and Technical Information (OSTI.GOV)

Norris, H; Rangaraj, D; Kim, S

Purpose: High-Z (metal) implants in CT scans cause significant streak-like artifacts in the reconstructed dataset. This results in both inaccurate CT Hounsfield units for the tissue as well as obscuration of the target and organs at risk (OARs) for radiation therapy planning. Herein we analyze two metal artifact reduction algorithms: GE’s Smart MAR and a Metal Deletion Technique (MDT) for geometric and Hounsfield Unit (HU) accuracy. Methods: A CT-to-electron density phantom, with multiple inserts of various densities and a custom Cerrobend insert (Zeff=76.8), is utilized in this continuing study. The phantom is scanned without metal (baseline) and again with themore » metal insert. Using one set of projection data, reconstructed CT volumes are created with filtered-back-projection (FBP) and the MAR and the MDT algorithms. Regions-of-Interest (ROIs) are evaluated for each insert for HU accuracy; the metal insert’s Full-Width-Half-Maximum (FWHM) is used to evaluate the geometric accuracy. Streak severity is quantified with an HU error metric over the phantom volume. Results: The original FBP reconstruction has a Root-Mean-Square-Error (RMSE) of 57.55 HU (STD=29.19, range=−145.8 to +79.2) compared to baseline. The MAR reconstruction has a RMSE of 20.98 HU (STD=13.92, range=−18.3 to +61.7). The MDT reconstruction has a RMSE of 10.05 HU (STD=10.5, range=−14.8 to +18.6). FWHM for baseline=162.05; FBP=161.84 (−0.13%); MAR=162.36 (+0.19%); MDT=162.99 (+0.58%). Streak severity metric for FBP=19.73 (22.659% bad pixels); MAR=8.743 (9.538% bad); MDT=4.899 (5.303% bad). Conclusion: Image quality, in terms of HU accuracy, in the presence of high-Z metal objects in CT scans is improved by metal artifact reduction reconstruction algorithms. The MDT algorithm had the highest HU value accuracy (RMSE=10.05 HU) and best streak severity metric, but scored the worst in terms of geometric accuracy. Qualitatively, the MAR and MDT algorithms increased detectability of inserts, although there is a loss of in-plane resolution near the metallic insert.« less

Evidence for Human Norovirus Infection of Dogs in the United Kingdom

PubMed Central

Emmott, Edward; El-Attar, Laila; Mitchell, Judy A.; Hollinshead, Michael; Belliot, Gael; Brownlie, Joe; Le Pendu, Jacques; Goodfellow, Ian

2015-01-01

Human noroviruses (HuNoVs) are a major cause of viral gastroenteritis, with an estimated 3 million cases per year in the United Kingdom. HuNoVs have recently been isolated from pet dogs in Europe (M. Summa, C.-H. von Bonsdorff, and L. Maunula, J Clin Virol 53:244–247, 2012, http://dx.doi.org/10.1016/j.jcv.2011.12.014), raising concerns about potential zoonotic infections. With 31% of United Kingdom households owning a dog, this could prove to be an important transmission route. To examine this risk, canine tissues were studied for their ability to bind to HuNoV in vitro. In addition, canine stool samples were analyzed for the presence of viral nucleic acid, and canine serum samples were tested for the presence of anti-HuNoV antibodies. The results showed that seven different genotypes of HuNoV virus-like particles (VLPs) can bind to canine gastrointestinal tissue, suggesting that infection is at least theoretically possible. Although HuNoV RNA was not identified in stool samples from 248 dogs, serological evidence of previous exposure to HuNoV was obtained in 43/325 canine serum samples. Remarkably, canine seroprevalence for different HuNoV genotypes mirrored the seroprevalence in the human population. Though entry and replication within cells have not been demonstrated, the canine serological data indicate that dogs produce an immune response to HuNoV, implying productive infection. In conclusion, this study reveals zoonotic implications for HuNoV, and to elucidate the significance of this finding, further epidemiological and molecular investigations will be essential. PMID:25832298

Optimization of SPECT-CT Hybrid Imaging Using Iterative Image Reconstruction for Low-Dose CT: A Phantom Study

PubMed Central

Grosser, Oliver S.; Kupitz, Dennis; Ruf, Juri; Czuczwara, Damian; Steffen, Ingo G.; Furth, Christian; Thormann, Markus; Loewenthal, David; Ricke, Jens; Amthauer, Holger

2015-01-01

Background Hybrid imaging combines nuclear medicine imaging such as single photon emission computed tomography (SPECT) or positron emission tomography (PET) with computed tomography (CT). Through this hybrid design, scanned patients accumulate radiation exposure from both applications. Imaging modalities have been the subject of long-term optimization efforts, focusing on diagnostic applications. It was the aim of this study to investigate the influence of an iterative CT image reconstruction algorithm (ASIR) on the image quality of the low-dose CT images. Methodology/Principal Findings Examinations were performed with a SPECT-CT scanner with standardized CT and SPECT-phantom geometries and CT protocols with systematically reduced X-ray tube currents. Analyses included image quality with respect to photon flux. Results were compared to the standard FBP reconstructed images. The general impact of the CT-based attenuation maps used during SPECT reconstruction was examined for two SPECT phantoms. Using ASIR for image reconstructions, image noise was reduced compared to FBP reconstructions for the same X-ray tube current. The Hounsfield unit (HU) values reconstructed by ASIR were correlated to the FBP HU values(R2 ≥ 0.88) and the contrast-to-noise ratio (CNR) was improved by ASIR. However, for a phantom with increased attenuation, the HU values shifted for low X-ray tube currents I ≤ 60 mA (p ≤ 0.04). In addition, the shift of the HU values was observed within the attenuation corrected SPECT images for very low X-ray tube currents (I ≤ 20 mA, p ≤ 0.001). Conclusion/Significance In general, the decrease in X-ray tube current up to 30 mA in combination with ASIR led to a reduction of CT-related radiation exposure without a significant decrease in image quality. PMID:26390216

Evaluation of the Effect of Hemoglobin or Hematocrit Level on Dural Sinus Density Using Unenhanced Computed Tomography

PubMed Central

Cha, Sang-Hoon; Lee, Sung-Hyun; Shin, Dong-Ick

2013-01-01

Purpose To identify the relationship between hemoglobin (Hgb) or hematocrit (Hct) level and dural sinus density using unenhanced computed tomography (UECT). Materials and Methods Patients who were performed UECT and had records of a complete blood count within 24 hours from UECT were included (n=122). We measured the Hounsfield unit (HU) of the dural sinus at the right sigmoid sinus, left sigmoid sinus and 2 points of the superior sagittal sinus. Quantitative measurement of dural sinus density using the circle regions of interest (ROI) method was calculated as average ROI values at 3 or 4 points. Simple regression analysis was used to evaluate the correlation between mean HU and Hgb or mean HU and Hct. Results The mean densities of the dural sinuses ranged from 24.67 to 53.67 HU (mean, 43.28 HU). There was a strong correlation between mean density and Hgb level (r=0.832) and between mean density and Hct level (r=0.840). Conclusion Dural sinus density on UECT is closely related to Hgb and Hct levels. Therefore, the Hgb or Hct levels can be used to determine whether the dural sinus density is within the normal range or pathological conditions such as venous thrombosis. PMID:23225795

Enhanced Androgen Signaling with Androgen Receptor Overexpression in the Osteoblast Lineage Controls Skeletal Turnover, Matrix Quality and Bone Architecture

DTIC Science & Technology

2009-12-01

calculatedbyconverting thegrayscale output of bone voxels in Hounsfield units (HU) to mineral values (mg/cc of HA) through the use of a calibration phantom...NUMBER Kristine M. Wiren, Ph.D. 5e. TASK NUMBER E-Mail: wirenk@ohsu.edu 5f. WORK UNIT NUMBER 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES...and d) characterization of effects of androgen on MSC colony forming units and lineage commitment in vitro. In this final report, we have included

There′s no place like home: Boarding surgical ICU patients in other ICUs and the effect of distances from the home unit

PubMed Central

Pascual, Jose L.; Blank, Nicholas W.; Holena, Daniel N.; Robertson, Matthew P.; Diop, Mouhamed; Allen, Steve R.; Martin, Niels D.; Kohl, Benjamin A.; Sims, Carrie A.; Schwab, C. William; Reilly, Patrick M.

2014-01-01

BACKGROUND Intensive care units (ICUs) function frequently at capacity, requiring incoming critically ill patients to be placed in alternate geographically distinct ICUs. In some medical ICU populations, “boarding” in an overflow ICU has been associated with increased mortality. We hypothesized that surgical ICU patients experience more complications when boarding in an overflow ICU and that the frequency of these complications are greatest in boarders farthest from the home unit (HU). METHODS A 5-year (June 2005 to June 2010) retrospective review of a prospectively maintained ICU database was performed, and demographics, severity of illness, length of stay, and incidence of ICU complications were extracted. Distances between boarding patients’ rooms and the HU were measured. Complications occurring in patients located in the same floor (BUSF) and different floor (BUDF) boarding units were compared and stratified by distance from HU to the patient room. Logistic regression was used to develop control for known confounders. RESULTS A total of 7,793 patients were admitted to the HU and 833 to a boarding unit (BUSF, n = 712; BUDF, n = 121). Boarders were younger, had a lower length of stay, and Acute Physiology and Chronic Health Evaluation II and were more of tentrauma/emergency surgery patients. Compared with in-HU patients, the incidence of aspiration pneumonia (2.2% vs. 3.6%, p < 0.01) was greater in BUSF patients and highest in those farthest from the HU (odds ratio [OR],2.39;p =0.01). Delirium occurred less often in HU than in BUDF patients (3.3% vs. 8.3 %, p < 0.01), and both delirium (OR, 6.09, p < 0.01) and ventilator-associated pneumonia (OR, 4.49, p < 0.05) were more frequent in patients farther from the HU. CONCLUSION Certain ICU complications occur more frequently in boarding patients particularly if they are located on a different floor or far from the HU. When surgical ICU bed availability forces overflow admissions to non–home ICUs, greater interdisciplinary awareness, education, and training may be needed to ensure equivalent care and outcomes. LEVEL OF EVIDENCE Epidemiologic study, level III. Therapeutic study, level IV. PMID:24662877

Physical analysis of breast cancer using dual-source computed tomography

NASA Astrophysics Data System (ADS)

Kim, H. J.; Lee, H. K.; Cho, J. H.

2014-12-01

This study was aimed to analyze various physical characteristics of breast cancer using dual-source computed tomography (CT). A phantom study and a clinical trial were performed in order and a 64-multidetector CT device was used for the examinations. In the phantom study, single-source (SS) CT was set up with a conventional scanning condition that is usually applied for breast CT examination and implementation was done at tube voltage of 120 kVp. Dual-source CT acquired images by irradiating X-ray sources with fast switching between two kilovoltage settings (80 and 140 kVp). After scanning, Hounsfield Unit (HU) values and radiation doses in a region of interest were measured and analyzed. In the clinical trial, the HU values were measured and analyzed after single-source computed tomography (SSCT) and dual-source CT in patients diagnosed with breast cancer. Also, the tumor size measured by dual-source CT was compared with the actual tumor size. The phantom study determined that the tumor region was especially measured by dual-source CT, while nylon fiber and specks region were especially measured by SSCT. The radiation dose was high with dual-source CT. The clinical trial showed a higher HU value of cancerous regions when scanned by dual-source CT compared with SSCT.

Hounsfield Unit Change in Root and Alveolar Bone during Canine Retraction

PubMed Central

Jiang, Feifei; Liu, Sean Y.; Xia, Zeyang; Li, Shuning; Chen, Jie; Kula, Katherine S.; Eckert, George

2014-01-01

Objectives The objective of this study was to determine the Hounsfield unit (HU) changes in the alveolar bone and root surface during controlled canine retractions. Methods Eighteen maxillary canine retraction patients were selected for this split mouth design clinical trial. The canines in each patient were randomly assigned to receive either translation or controlled tipping treatment strategy. Pre- and post-treatment cone beam computed tomography scans of each patient were used to determine tooth movement direction and HU changes. The alveolar bone and root surface were divided into 108 divisions, respectively. The HU in each division was measured. The Mixed-model ANOVA was applied to test the HU change distribution at the p<0.05 significant level. Results The HU changes varied with the directions relative to the canine movement. The HU reduction occurred at the root surface. Larger reductions occurred in the divisions that were perpendicular to the moving direction. However, HU decreased in the alveolar bone in the moving direction. The highest HU reduction was at the coronal level. Conclusions HU reduction occurs on the root surface in the direction perpendicular to the tooth movement and in the alveolar bone in the direction of tooth movement when a canine is retracted. PMID:25836004

Pathology Observed on Cone Beam Computed Tomographic Scans: A Comparison of Prevalence and Type of Incidental Findings for Child/Adolescents and Adults

DTIC Science & Technology

2013-04-13

the radiation passed through the subject. For conventional CT, this value is called a Hounsfield unit (HU), named in the honor of Godfrey Hounsfield ...concretions and tonsilloliths. Otolaryngol Clin North Am. 1987 May;20(2):305-9. 39. Reeves TE, Mah P, McDavid WD. Deriving Hounsfield units using grey...study are those of the authors and do not reflect the official policy of the United States Air Force, the Department of Defense, or the United States

Technical Note: Relation between dual-energy subtraction of CT images for electron density calibration and virtual monochromatic imaging.

PubMed

Saito, Masatoshi

2015-07-01

For accurate tissue inhomogeneity correction in radiotherapy treatment planning, the author previously proposed a simple conversion of the energy-subtracted computed tomography (CT) number to an electron density (ΔHU-ρe conversion), which provides a single linear relationship between ΔHU and ρe over a wide ρe range. The purpose of the present study was to reveal the relation between the ΔHU image for ρe calibration and a virtually monochromatic CT image by performing numerical analyses based on the basis material decomposition in dual-energy CT. The author determined the weighting factor, α0, of the ΔHU-ρe conversion through numerical analyses of the International Commission on Radiation Units and Measurements Report-46 human body tissues using their attenuation coefficients and given ρe values. Another weighting factor, α(E), for synthesizing a virtual monochromatic CT image from high- and low-kV CT images, was also calculated in the energy range of 0.03 < E < 5 MeV, assuming that cortical bone and water were the basis materials. The mass attenuation coefficients for these materials were obtained using the xcom photon cross sections database. The effective x-ray energies used to calculate the attenuation were chosen to imitate a dual-source CT scanner operated at 80-140 and 100-140 kV/Sn. The determined α0 values were 0.455 for 80-140 kV/Sn and 0.743 for 100-140 kV/Sn. These values coincided almost perfectly with the respective maximal points of the calculated α(E) curves located at approximately 1 MeV, in which the photon-matter interaction in human body tissues is exclusively the incoherent (Compton) scattering. The ΔHU image could be regarded substantially as a CT image acquired with monoenergetic 1-MeV photons, which provides a linear relationship between CT numbers and electron densities.

Wildlife Impact Assessment : Bonneville, McNary, The Dalles, and John Day Projects.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rasmussen, Larry; Wright, Patrick

1990-10-01

The Habitat Evaluation Procedures (HEP) were used to evaluate pre- and post-construction habitat conditions of the US Army Corps of Engineers Bonneville project in Oregon and Washington. The project directly impacted 20,749 acres of wildlife habitat. Seven evaluation species were selected with losses and gains expressed in Habitat Units (HU's). One HU is equivalent to 1 acre of prime habitat. The evaluation estimated a gain of 2671 HU's of lesser scaup wintering habitat. Losses of 4300 HU's of great blue heron habitat, 2443 HU's of Canada goose habitat, 2767 HU's of spotted sandpiper habitat, 163 HU's of yellow warbler habitat,more » 1022 HU's black-capped chickadee habitat, and 1622 HU's of mink habitat occurred as a result of the project. This amounts to a total combined loss of 12,317 HU's. 18 refs., 1 fig., 4 tabs.« less

[Detection of intraorbital foreign material using MDCT].

PubMed

Hoffstetter, P; Friedrich, C; Framme, C; Hoffstetter, M; Zorger, N; Stierstorfer, K; Ross, C; Uller, W; Müller-Wille, R; Rennert, J; Jung, E M; Schreyer, A G

2011-06-01

To judge the possibilities of detection of orbital foreign bodies in multidetector CT (MDCT) with a focus on glass slivers. Experimental systematic measuring of Hounsfield Units (HU) of 20 different materials, containing 16 different types of glass with 4 different types of ophthalmic lenses among them. The measurements were performed using a standardized protocol with an orbita phantom being scanned with 16-slice MDCT. Using the resulting density values, the smallest detectable volume was calculated. Using this data we produced slivers of 5 different glass types in the sub-millimeter range and calculated their volume. Those micro-slivers underwent another CT scan using the same protocol as mentioned above to experimentally discern and confirm the detection limit for micro-slivers made of different materials. Glass has comparatively high density values of at least 2000 HU. The density of glasses with strong refraction is significantly higher and reaches up to 12 400 HU. We calculated a minimum detectable volume of 0.07 mm (3) for glass with a density of 2000 HU. Only glass slivers with a density higher than 8300 HU were experimentally detectable in the sub-millimeter range up to a volume as small as 0.01 mm (3). Less dense glass slivers could not be seen, even though their volume was above the theoretically calculated threshold for detection. Due to its high density of at least 2000 HU, glass is usually easily recognizable as an orbital foreign body. The detection threshold depends on the object's density and size and can be as low as 0.01 mm (3) in the case of glass with strong refraction and thus high density. The detection of glass as an orbital foreign body seems to be secure for slivers with a volume of at least 0.2 mm (3) for all types of glass. © Georg Thieme Verlag KG Stuttgart · New York.

Bone mineral density loss in thoracic and lumbar vertebrae following radiation for abdominal cancers.

PubMed

Wei, Randy L; Jung, Brian C; Manzano, Wilfred; Sehgal, Varun; Klempner, Samuel J; Lee, Steve P; Ramsinghani, Nilam S; Lall, Chandana

2016-03-01

To investigate the relationship between abdominal chemoradiation (CRT) for locally advanced cancers and bone mineral density (BMD) reduction in the vertebral spine. Data from 272 patients who underwent abdominal radiation therapy from January 1997 to May 2015 were retrospectively reviewed. Forty-two patients received computed tomography (CT) scans of the abdomen prior to initiation and at least twice after radiation therapy. Bone attenuation (in Hounsfield unit) (HU) measurements were collected for each vertebral level from T7 to L5 using sagittal CT images. Radiation point dose was obtained at each mid-vertebral body from the radiation treatment plan. Percent change in bone attenuation (Δ%HU) between baseline and post-radiation therapy were computed for each vertebral body. The Δ%HU was compared against radiation dose using Pearson's linear correlation. Abdominal radiotherapy caused significant reduction in vertebral BMD as measured by HU. Patients who received only chemotherapy did not show changes in their BMD in this study. The Δ%HU was significantly correlated with the radiation point dose to the vertebral body (R=-0.472, P<0.001) within 4-8 months following RT. The same relationship persisted in subsequent follow up scans 9 months following RT (R=-0.578, P<0.001). Based on the result of linear regression, 5 Gy, 15 Gy, 25 Gy, 35 Gy, and 45 Gy caused 21.7%, 31.1%, 40.5%, 49.9%, and 59.3% decrease in HU following RT, respectively. Our generalized linear model showed that pre-RT HU had a positive effect (β=0.830) on determining post-RT HU, while number of months post RT (β=-0.213) and radiation point dose (β=-1.475) had a negative effect. A comparison of the predicted versus actual HU showed significant correlation (R=0.883, P<0.001) with the slope of the best linear fit=0.81. Our model's predicted HU were within ±20 HU of the actual value in 53% of cases, 70% of the predictions were within ±30 HU, 81% were within ±40 HU, and 90% were within ±50 HU of the actual post-RT HU. Four of 42 patients were found to have vertebral body compression fractures in the field of radiation. Patients who receive abdominal chemoradiation develop significant BMD loss in the thoracic and lumbar vertebrae. Treatment-related BMD loss may contribute to the development of vertebral compression fractures. A predictive model for post-CRT BMD changes may inform bone protective strategies in patients planned for abdominal CRT. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

A retrospective comparison of smart prep and test bolus multi-detector CT pulmonary angiography protocols

DOE Office of Scientific and Technical Information (OSTI.GOV)

Suckling, Tara; Smith, Tony; Reed, Warren

2013-06-15

Optimal arterial opacification is crucial in imaging the pulmonary arteries using computed tomography (CT). This poses the challenge of precisely timing data acquisition to coincide with the transit of the contrast bolus through the pulmonary vasculature. The aim of this quality assurance exercise was to investigate if a change in CT pulmonary angiography (CTPA) scanning protocol resulted in improved opacification of the pulmonary arteries. Comparison was made between the smart prep protocol (SPP) and the test bolus protocol (TBP) for opacification in the pulmonary trunk. A total of 160 CTPA examinations (80 using each protocol) performed between January 2010 andmore » February 2011 were assessed retrospectively. CT attenuation coefficients were measured in Hounsfield Units (HU) using regions of interest at the level of the pulmonary trunk. The average pixel value, standard deviation (SD), maximum, and minimum were recorded. For each of these variables a mean value was then calculated and compared for these two CTPA protocols. Minimum opacification of 200 HU was achieved in 98% of the TBP sample but only 90% of the SPP sample. The average CT attenuation over the pulmonary trunk for the SPP was 329 (SD = ±21) HU, whereas for the TBP it was 396 (SD = ±22) HU (P = 0.0017). The TBP also recorded higher maximum (P = 0.0024) and minimum (P = 0.0039) levels of opacification. This study has found that a TBP resulted in significantly better opacification of the pulmonary trunk than the SPP.« less

X-ray computed tomography to study rice (Oryza sativa L.) panicle development

PubMed Central

Jhala, Vibhuti M.; Thaker, Vrinda S.

2015-01-01

Computational tomography is an important technique for developing digital agricultural models that may help farmers and breeders for increasing crop quality and yield. In the present study an attempt has been made to understand rice seed development within the panicle at different developmental stages using this technique. During the first phase of cell division the Hounsfield Unit (HU) value remained low, increased in the dry matter accumulation phase, and finally reached a maximum at the maturation stage. HU value and seed dry weight showed a linear relationship in the varieties studied. This relationship was confirmed subsequently using seven other varieties. This is therefore an easy, simple, and non-invasive technique which may help breeders to select the best varieties. In addition, it may also help farmers to optimize post-anthesis agronomic practices as well as deciding the crop harvest time for higher grain yield. PMID:26265763

Low-dose lung cancer screening with photon-counting CT: a feasibility study

NASA Astrophysics Data System (ADS)

Symons, Rolf; Cork, Tyler E.; Sahbaee, Pooyan; Fuld, Matthew K.; Kappler, Steffen; Folio, Les R.; Bluemke, David A.; Pourmorteza, Amir

2017-01-01

To evaluate the feasibility of using a whole-body photon-counting detector (PCD) CT scanner for low-dose lung cancer screening compared to a conventional energy integrating detector (EID) system. Radiation dose-matched EID and PCD scans of the COPDGene 2 phantom were acquired at different radiation dose levels (CTDIvol: 3.0, 1.5, and 0.75 mGy) and different tube voltages (120, 100, and 80 kVp). EID and PCD images were compared for quantitative Hounsfield unit (HU) accuracy, noise levels, and contrast-to-noise ratios (CNR) for detection of ground-glass nodules (GGN) and emphysema. The PCD HU accuracy was better than EID for water at all scan parameters. PCD HU stability for lung, GGN and emphysema regions were superior to EID and PCD attenuation values were more reproducible than EID for all scan parameters (all P  <  0.01), while HUs for lung, GGN and emphysema ROIs changed significantly for EID with decreasing dose (all P  <  0.001). PCD showed lower noise levels at the lowest dose setting at 120, 100 and 80 kVp (15.2  ±  0.3 HU versus 15.8  ±  0.2 HU, P  =  0.03 16.1  ±  0.3 HU versus 18.0  ±  0.4 HU, P  =  0.003 and 16.1  ±  0.3 HU versus 17.9  ±  0.3 HU, P  =  0.001, respectively), resulting in superior CNR for evaluation of GGNs and emphysema at 100 and 80 kVp. PCD provided better HU stability for lung, ground-glass, and emphysema-equivalent foams at lower radiation dose settings with better reproducibility than EID. Additionally, PCD showed up to 10% less noise, and 11% higher CNR at 0.75 mGy for both 100 and 80 kVp. PCD technology may help reduce radiation exposure in lung cancer screening while maintaining diagnostic quality.

High dose microCT does not contribute towards improved microPET/CT image quantitative accuracy and can limit longitudinal scanning of small animals

NASA Astrophysics Data System (ADS)

McDougald, Wendy A.; Collins, Richard; Green, Mark; Tavares, Adriana A. S.

2017-10-01

Obtaining accurate quantitative measurements in preclinical Positron Emission Tomography/Computed Tomography (PET/CT) imaging is of paramount importance in biomedical research and helps supporting efficient translation of preclinical results to the clinic. The purpose of this study was two-fold: (1) to investigate the effects of different CT acquisition protocols on PET/CT image quality and data quantification; and (2) to evaluate the absorbed dose associated with varying CT parameters. Methods: An air/water quality control CT phantom, tissue equivalent material phantom, an in-house 3D printed phantom and an image quality PET/CT phantom were imaged using a Mediso nanoPET/CT scanner. Collected data was analyzed using PMOD software, VivoQuant software and National Electric Manufactures Association (NEMA) software implemented by Mediso. Measured Hounsfield Unit (HU) in collected CT images were compared to the known HU values and image noise was quantified. PET recovery coefficients (RC), uniformity and quantitative bias were also measured. Results: Only less than 2% and 1% of CT acquisition protocols yielded water HU values < -80 and air HU values < -840, respectively. Four out of eleven CT protocols resulted in more than 100 mGy absorbed dose. Different CT protocols did not impact PET uniformity and RC, and resulted in <4% overall bias relative to expected radioactive concentration. Conclusion: Preclinical CT protocols with increased exposure times can result in high absorbed doses to the small animals. These should be avoided, as they do not contributed towards improved microPET/CT image quantitative accuracy and could limit longitudinal scanning of small animals.

Segmentation and Estimation of the Histological Composition of the Tumor Mass in Computed Tomographic Images of Neuroblastoma

DTIC Science & Technology

2001-10-25

a CT image, each voxel contains an integer number which is the CT value, in Hounsfield units (HU), of the voxel. Therefore, the standard method of...Task Number Work Unit Number Performing Organization Name(s) and Address(es) Department of Electrical and Computer Engineering, University of...34, Journal of Pediatric Surgery, vol 24(7), pp. 708-711, 1989. [4] I. N. Bankman, editor, Handbook of Medical Image Analysis, Academic Press, London, UK

Hounsfield unit change in root and alveolar bone during canine retraction.

PubMed

Jiang, Feifei; Liu, Sean S-Y; Xia, Zeyang; Li, Shuning; Chen, Jie; Kula, Katherine S; Eckert, George

2015-04-01

The objective of this study was to determine the Hounsfield unit (HU) changes in the alveolar bone and root surfaces during controlled canine retractions. Eighteen maxillary canine retraction patients were selected for this split-mouth design clinical trial. The canines in each patient were randomly assigned to receive either translation or controlled tipping treatment. Pretreatment and posttreatment cone-beam computed tomography scans of each patient were used to determine tooth movement direction and HU changes. The alveolar bone and root surface were divided into 108 divisions, respectively. The HUs in each division were measured. Mixed-model analysis of variance was applied to test the HU change distribution at the P <0.05 significance level. The HU changes varied with the directions relative to the canine movement. The HU reductions occurred at the root surfaces. Larger reductions occurred in the divisions that were perpendicular to the moving direction. However, HUs decreased in the alveolar bone in the moving direction. The highest HU reduction was at the coronal level. HU reduction occurs on the root surface in the direction perpendicular to tooth movement and in the alveolar bone in the direction of tooth movement when a canine is retracted. Copyright © 2015 American Association of Orthodontists. Published by Elsevier Inc. All rights reserved.

Sacral Bone Mass Distribution Assessed by Averaged Three-Dimensional CT Models: Implications for Pathogenesis and Treatment of Fragility Fractures of the Sacrum.

PubMed

Wagner, Daniel; Kamer, Lukas; Sawaguchi, Takeshi; Richards, R Geoff; Noser, Hansrudi; Rommens, Pol M

2016-04-06

Fragility fractures of the sacrum are increasing in prevalence due to osteoporosis and epidemiological changes and are challenging in their treatment. They exhibit specific fracture patterns with unilateral or bilateral fractures lateral to the sacral foramina, and sometimes an additional transverse fracture leads to spinopelvic dissociation. The goal of this study was to assess sacral bone mass distribution and corresponding changes with decreased general bone mass. Clinical computed tomography (CT) scans of intact pelves in ninety-one individuals (mean age and standard deviation, 61.5 ± 11.3 years) were used to generate three-dimensional (3D) models of the sacrum averaging bone mass in Hounsfield units (HU). Individuals with decreased general bone mass were identified by measuring bone mass in L5 (group 1 with <100 HU; in contrast to group 2 with ≥100 HU). In group 1, a large zone of negative Hounsfield units was located in the paraforaminal lateral region from S1 to S3. Along the trans-sacral corridors, a Hounsfield unit peak was observed laterally, corresponding to cortical bone of the auricular surface. The lowest Hounsfield unit values were found in the paraforaminal lateral region in the sacral ala. An intermediate level of bone mass was observed in the area of the vertebral bodies, which also demonstrated the largest difference between groups 1 and 2. Overall, the Hounsfield units were lower at S2 than S1. The models of averaged bone mass in the sacrum revealed a distinct 3D distribution pattern. The negative values in the paraforaminal lateral region may explain the specific fracture patterns in fragility fractures of the sacrum involving the lateral areas of the sacrum. Transverse fractures located between S1 and S2 leading to spinopelvic dissociation may occur because of decreased bone mass in S2. The largest difference between the studied groups was found in the vertebral bodies and might support the use of transsacral or cement-augmented implants. Copyright © 2016 by The Journal of Bone and Joint Surgery, Incorporated.

Dual energy micro CT SkyScan 1173 for the characterization of urinary stone

NASA Astrophysics Data System (ADS)

Fitri, L. A.; Asyana, V.; Ridwan, T.; Anwary, F.; Soekersi, H.; Latief, F. D. E.; Haryanto, F.

2016-03-01

Knowledge of the composition of urinary stones is an essential part to determine suitable treatments for patients. The aim of this research is to characterize the urinary stones by using dual energy micro CT SkyScan 11173. This technique combines high-energy and low- energy scanning during a single acquisition. Six human urinary stones were scanned in vitro using 80 kV and 120 kV micro CT SkyScan 1173. Projected images were produced by micro CT SkyScan 1173 and then reconstructed using NRecon (in-house software from SkyScan) to obtain a complete 3D image. The urinary stone images were analysed using CT analyser to obtain information of internal structure and Hounsfield Unit (HU) values to determine the information regarding the composition of the urinary stones, respectively. HU values obtained from some regions of interest in the same slice are compared to a reference HU. The analysis shows information of the composition of the six scanned stones obtained. The six stones consist of stone number 1 (calcium+cystine), number 2 (calcium+struvite), number 3 (calcium+cystine+struvite), number 4 (calcium), number 5 (calcium+cystine+struvite), and number 6 (calcium+uric acid). This shows that dual energy micro CT SkyScan 1173 was able to characterize the composition of the urinary stone.

Technology of research of hydroturbine unit work using seismic methods

NASA Astrophysics Data System (ADS)

Seleznev, V. S.; Liseikin, A. V.; Gromyko, P. V.; Soloviev, V. M.

2013-05-01

On August, 17, 2009 one of the most significant accident in hydropower engineering was happened at Sayano-Shushenskaya Hydroelectric Power Station. Specialists of Geophysical Survey SB RAS took part in the State Committee on investigation of the accident cause at Sayano-Shushenskaya HPS. It was determined, that the cause of the accident was a break of stud-bolts on the turbine cover. Why stud-bolts did not stand a load? There were assumptions that hydraulic shock provoked the accident. But, if it is so, seismic station "Cheremushky", situated in 4 km away from the HPS, should has a record of this event. First of all, investigating the record, got at the seismic station in the moment of the accident, it was determined that strength of seismic waves, recorded at the moment of the accident, did not exceed strength of waves got at trotyl explosion of 500 g at a distance to 4 km. The version of hydraulic shock was not proved. There were distinguished low-frequency oscillations and it was determined that the hydroturbine unit (HU) had been raised up more then 10 m in height for 10 sec. Analyzing the seismic station records during the period of more than a year before the accident and records of operating modes of different HU, there was determined that oscillations radiated by second (damaged) HU were approximately 1.5 times more intense than oscillations from all other HU. After the accident at Sayano-Shushenskaya HPS hydroturbine units were started in turns: at first there were started hydroturbine units of old construction (3, 4, 5, 6), then HP of new construction (1, 7, 8, 9). We installed 10 - 15 three-component seismic stations in different points around a HU and studied field of seismic oscillations from it's work. It was determined, that HU radiates a set of monochromatic oscillations divisible by speed of rotation equal to 2.381 Hz. Change of these signals amplitude is connected with change of HU operation modes. Research of changes in oscillations spectral distribution in time allows to control HU work and it's technical condition. It was determined, that natural frequency of turbine cover (when water entry is closed) has several maximums, and it is situated in the range of 60 - 110 Hz. Power radiation of monochromatic signals is registered in the same range from old hydroturbine units when they work, especially on double blade frequency equal to 76.2 Hz. It turns out that the turbine cover and fixed it stud-bolts were in condition of constant resonance excitation during work of HU. Since second HU was arranged in such a way that oscillations radiated by it exceeded oscillations from other aggregates, the accident occurred exactly on this HU. The real cause of the accident is connected with the fact that at calculation of the turbine cover fastening it was not taken into account the fact that it would work in constant resonance excitation. On new constructed HU number of stud-bolts was increased and the amplitude of monochromatic oscillations was considerably reduced.

Evaluation of Chlorine Treatment Levels for Inactivation of Human Norovirus and MS2 Bacteriophage during Sewage Treatment.

PubMed

Kingsley, David H; Fay, Johnna P; Calci, Kevin; Pouillot, Régis; Woods, Jacquelina; Chen, Haiqiang; Niemira, Brendan A; Van Doren, Jane M

2017-12-01

This study examined the inactivation of human norovirus (HuNoV) GI.1 and GII.4 by chlorine under conditions mimicking sewage treatment. Using a porcine gastric mucin-magnetic bead (PGM-MB) assay, no statistically significant loss in HuNoV binding (inactivation) was observed for secondary effluent treatments of ≤25 ppm total chlorine; for both strains, 50 and 100 ppm treatments resulted in ≤0.8-log 10 unit and ≥3.9-log 10 unit reductions, respectively. Treatments of 10, 25, 50, and 100 ppm chlorine inactivated 0.31, 1.35, >5, and >5 log 10 units, respectively, of the norovirus indicator MS2 bacteriophage. Evaluation of treatment time indicated that the vast majority of MS2 and HuNoV inactivation occurred in the first 5 min for 0.2-μm-filtered, prechlorinated secondary effluent. Free chlorine measurements of secondary effluent seeded with MS2 and HuNoV demonstrated substantial oxidative burdens. With 25, 50, and 100 ppm treatments, free chlorine levels after 5 min of exposure ranged from 0.21 to 0.58 ppm, from 0.28 to 16.7 ppm, and from 11.6 to 53 ppm, respectively. At chlorine treatment levels of >50 ppm, statistically significant differences were observed between reductions for PGM-MB-bound HuNoV (potentially infectious) particles and those for unbound (noninfectious) HuNoV particles or total norovirus particles. While results suggested that MS2 and HuNoV (measured as PGM-MB binding) behave similarly, although not identically, both have limited susceptibility to chlorine treatments of ≤25 ppm total chlorine. Since sewage treatment is performed at ≤25 ppm total chlorine, targeting free chlorine levels of 0.5 to 1.0 ppm, these results suggest that traditional chlorine-based sewage treatment does not inactivate HuNoV efficiently. IMPORTANCE HuNoV is ubiquitous in sewage. A receptor binding assay was used to assess inactivation of HuNoV by chlorine-based sewage treatment, given that the virus cannot be routinely propagated in vitro Results reported here indicate that chlorine treatment of sewage is not effective for inactivating HuNoV unless chlorine levels are above those routinely used for sewage treatment. Copyright © 2017 American Society for Microbiology.

Evaluation of Chlorine Treatment Levels for Inactivation of Human Norovirus and MS2 Bacteriophage during Sewage Treatment

PubMed Central

Fay, Johnna P.; Calci, Kevin; Pouillot, Régis; Woods, Jacquelina; Chen, Haiqiang; Niemira, Brendan A.; Van Doren, Jane M.

2017-01-01

ABSTRACT This study examined the inactivation of human norovirus (HuNoV) GI.1 and GII.4 by chlorine under conditions mimicking sewage treatment. Using a porcine gastric mucin-magnetic bead (PGM-MB) assay, no statistically significant loss in HuNoV binding (inactivation) was observed for secondary effluent treatments of ≤25 ppm total chlorine; for both strains, 50 and 100 ppm treatments resulted in ≤0.8-log10 unit and ≥3.9-log10 unit reductions, respectively. Treatments of 10, 25, 50, and 100 ppm chlorine inactivated 0.31, 1.35, >5, and >5 log10 units, respectively, of the norovirus indicator MS2 bacteriophage. Evaluation of treatment time indicated that the vast majority of MS2 and HuNoV inactivation occurred in the first 5 min for 0.2-μm-filtered, prechlorinated secondary effluent. Free chlorine measurements of secondary effluent seeded with MS2 and HuNoV demonstrated substantial oxidative burdens. With 25, 50, and 100 ppm treatments, free chlorine levels after 5 min of exposure ranged from 0.21 to 0.58 ppm, from 0.28 to 16.7 ppm, and from 11.6 to 53 ppm, respectively. At chlorine treatment levels of >50 ppm, statistically significant differences were observed between reductions for PGM-MB-bound HuNoV (potentially infectious) particles and those for unbound (noninfectious) HuNoV particles or total norovirus particles. While results suggested that MS2 and HuNoV (measured as PGM-MB binding) behave similarly, although not identically, both have limited susceptibility to chlorine treatments of ≤25 ppm total chlorine. Since sewage treatment is performed at ≤25 ppm total chlorine, targeting free chlorine levels of 0.5 to 1.0 ppm, these results suggest that traditional chlorine-based sewage treatment does not inactivate HuNoV efficiently. IMPORTANCE HuNoV is ubiquitous in sewage. A receptor binding assay was used to assess inactivation of HuNoV by chlorine-based sewage treatment, given that the virus cannot be routinely propagated in vitro. Results reported here indicate that chlorine treatment of sewage is not effective for inactivating HuNoV unless chlorine levels are above those routinely used for sewage treatment. PMID:28939600

Hydroxyapatite ceramic implants for cranioplasty in children: a single-center experience.

PubMed

Zaccaria, Laura; Tharakan, Sasha Job; Altermatt, Stefan

2017-02-01

The use of hydroxyapatite ceramic (HAC) implants for the treatment of skull defects in pediatric patients started 2010 at our institution. Ceramic implants facilitate osteoblast migration and therefore optimize osteointegration with the host bone. The purpose of this study is to report a single-center experience with this treatment modality. A retrospective review of all patients from July 2010 through June 2014 undergoing a cranioplasty using hydroxyapatite ceramic implant and managed at a single institution was performed. Indication for cranioplasty, the hospital course, and follow-up were reviewed. Bone density was measured in Hounsfield Units (HU) and osteointegration was calculated using Mimics Software® (Mimics Innovation Suite v17.0 Medical, Materialize, Leuven, Belgium). Over the 4-year period, six patients met criteria for the study. Five patients had an osteointegration of nearly 100%. One patient had an incomplete osteointegration with a total bone-implant contact area of 69%. The mean bone density was 2800 HU (2300-3000 HU). Bone density alone is estimated to have a Hounsfield value between 400 and 2000 HU depending on the body region and bone quality. There were no major complications, and the patients were highly satisfied with the esthetical result. Hydroxyapatite ceramic implants for cranioplasty in pediatric patients are a good choice for different indications. The implants show excellent osteointegration and esthetical results.

SedCT: MATLAB™ tools for standardized and quantitative processing of sediment core computed tomography (CT) data collected using a medical CT scanner

NASA Astrophysics Data System (ADS)

Reilly, B. T.; Stoner, J. S.; Wiest, J.

2017-08-01

Computed tomography (CT) of sediment cores allows for high-resolution images, three-dimensional volumes, and down core profiles. These quantitative data are generated through the attenuation of X-rays, which are sensitive to sediment density and atomic number, and are stored in pixels as relative gray scale values or Hounsfield units (HU). We present a suite of MATLAB™ tools specifically designed for routine sediment core analysis as a means to standardize and better quantify the products of CT data collected on medical CT scanners. SedCT uses a graphical interface to process Digital Imaging and Communications in Medicine (DICOM) files, stitch overlapping scanned intervals, and create down core HU profiles in a manner robust to normal coring imperfections. Utilizing a random sampling technique, SedCT reduces data size and allows for quick processing on typical laptop computers. SedCTimage uses a graphical interface to create quality tiff files of CT slices that are scaled to a user-defined HU range, preserving the quantitative nature of CT images and easily allowing for comparison between sediment cores with different HU means and variance. These tools are presented along with examples from lacustrine and marine sediment cores to highlight the robustness and quantitative nature of this method.

Delivery of Nano-Tethered Therapies to Brain Metastases of Primary Breast Cancer Using a Cellular Trojan Horse

DTIC Science & Technology

2015-10-01

tomography images. The CT image densities in Hounsfield units (HU) of the brain were translated into corresponding optical properties (absorption...derived the Hounsfield units and optical properties of brain tissues such as white/gray matter. 13-15 The segmentation software generated an optical map...treatment protocol. Head CT image densities (in Hounsfield Units /HU) are segmented and translated into optical properties of the brain tissue

Delivery of Nano-Tethered Therapies to Brain Metastases of Primary Breast Cancer Using a Cellular Trojan Horse

DTIC Science & Technology

2015-12-01

Hounsfield units (HU) of the brain were translated into corresponding optical properties (absorption coefficient, scattering coefficient, and anisotropy...factor) using lookup tables (Fig 2). The lookup tables were prepared from earlier studies which derived the Hounsfield units and optical properties of... Hounsfield Units /HU) are segmented and translated into optical properties of the brain tissue (white/gray matter, CSF, skull bone, etc.). Monte

Low-dose CT for quantitative analysis in acute respiratory distress syndrome

DTIC Science & Technology

2013-08-31

noise of scans performed at 140, 60, 15 and 7.5 mAs corresponded to 10, 16, 38 and 74 Hounsfield Units , respectively. Conclusions: A reduction of...slice of a series, total lung volume, total lung tissue mass and frequency distribution of lung CT numbers expressed in Hounsfield Units (HU) were...tomography; HU: Hounsfield units ; CTDIvol: volumetric computed tomography dose index; DLP: dose length product; E: effective dose; SD: standard deviation

Quantitative characterization of liver tumor radiodensity in CT images: a phantom study between two scanners

NASA Astrophysics Data System (ADS)

Berman, Benjamin Paul; Li, Qin; McKenney, Sarah; Fricke, Stanley Thomas; Fang, Yuan; Gavrielides, Marios A.; Petrick, Nicholas

2018-02-01

Quantitative assessment of tumor radiodensity is important for the clinical evaluation of contrast enhancement and treatment response, as well as for the extraction of texture-related features for image analysis or radiomics. Radiodensity estimation, Hounsfield Units (HU) in CT images, can be affected by patient factors such as tumor size, and by system factors such as acquisition and reconstruction protocols. In this project, we quantified the measurability of liver tumor HU using a 3D-printed phantom, imaged with two CT systems: Siemens Somatom Force and GE Lightspeed VCT. The phantom was printed by dithering two materials to create spherical tumors (10, 14 mm) with uniform densities (90, 95, 100, 105 HU). Image datasets were acquired at 120 kVp including 15 repeats using two matching exposures across the CT systems, and reconstructed using comparable algorithms. The radiodensity of each tumor was measured using an automated matched-filter method. We assessed the performance of each protocol using the area under the ROC curve (AUC) as the metric for distinguishing between tumors with different radiodensities. The AUC ranged from 0.8 to 1.0 and was affected by tumor size, radiodensity, and scanner; the lowest AUC values corresponded to low dose measurements of 10 mm tumors with less than 5 HU difference. The two scanners exhibited similar performance >0.9 AUC for large lesions with contrast above 7 HU, though differences were observed for the smallest and lowest contrast tumors. These results show that HU estimation should be carefully examined, considering that uncertainty in the tumor radiodensity may propagate to quantification of other characteristics, such as size and texture.

Examination of forensic entomology evidence using computed tomography scanning: case studies and refinement of techniques for estimating maggot mass volumes in bodies.

PubMed

Johnson, Aidan; Archer, Melanie; Leigh-Shaw, Lyndie; Pais, Mike; O'Donnell, Chris; Wallman, James

2012-09-01

A new technique has recently been developed for estimating the volume of maggot masses on deceased persons using post-mortem CT scans. This allows volume to be measured non-invasively and factored into maggot mass temperature calculations for both casework and research. Examination of admission scans also allows exploration of entomological evidence in anatomical areas not usually exposed by autopsy (e.g. nasal cavities and facial sinuses), and before autopsy disrupts the maggot distribution on a body. This paper expands on work already completed by providing the x-ray attenuation coefficient by way of Hounsfield unit (HU) values for various maggot species, maggot masses and human tissue adjacent to masses. Specifically, this study looked at the HU values for four forensically important blowfly larvae: Lucilia cuprina, L. sericata, Calliphora stygia and C. vicina. The Calliphora species had significantly lower HU values than the Lucilia species. This might be explained by histological analysis, which revealed a non-significant trend, suggesting that Calliphora maggots have a higher fat content than the Lucilia maggots. It is apparent that the variation in the x-ray attenuation coefficient usually precludes its use as a tool for delineating the maggot mass from human tissue and that morphology is the dominant method for delineating a mass. This paper also includes three case studies, which reveal different applications for interpreting entomological evidence using post-mortem CT scans.

Evaluation of the CT Parameters to Suppress Renal Cysts Pseudoenhancement Effect: Influence of the Virtual Monochromatic Spectral Images, the Model-based Iterative Reconstruction Algorithm and the Aperture Size in Phantom Model.

PubMed

Sugisawa, Koichi; Ichikawa, Katsuhiro; Minamishima, Kazuya; Hasegawa, Masakazu; Yamada, Yoshitake; Jinzaki, Masahiro

2017-01-01

The purpose of this study was to evaluate the effect of the virtual monochromatic spectral images (VMSI) and the model-based iterative reconstruction (MBIR) images, to evaluate the influence of the aperture size (40- and 20-mm beam) on renal pseudoenhancement (PE) compared with the filtered back projection (FBP) images. The renal compartment-CT phantom was filled with iodinated contrast material diluted to the attenuation of 180 Hounsfield units (HU) at 120 kV. The water-filled spherical structures, which simulate cyst, were inserted into the renal compartment. Those diameters were 7, 15 and 25 mm. These were scanned by conventional mode (helical scan, 120 kV-FBP) and dual energy mode. 70 keV-VMSI were reconstructed from the dual energy mode, and MBIR images were reconstructed from conventional mode at 40- and 20-mm aperture. Additionally, the phantom was scanned using non-helical mode with 20-mm aperture, and FBP images were reconstructed. The CT value of the PE for cyst areas was measured for these images. The CT values of the cysts were 20.0-14.3 HU on the FBP images, 12.8-12.7 HU on the 70 keV-VMSI (PE-inhibition ratio was 36.0-11.2%) and 16.2-14.0 HU on the MBIR images (19.0-2.1%), respectively, at 40-mm aperture. The PE-inhibition ratio scanned by 20-mm aperture was improved by 28.0% with FBP, 32.8% with 70 keV-VMSI and 29.6% with MBIR compared with 40-mm aperture. One of the FBP images with non-helical mode was 11.6 HU. The best CT technique to minimize PE was the combination of 70 keV-VMSI and 20-mm aperture.

Evaluation of quantitative parameters for distinguishing pheochromocytoma from other adrenal tumors.

PubMed

Ohno, Youichi; Sone, Masakatsu; Taura, Daisuke; Yamasaki, Toshinari; Kojima, Katsutoshi; Honda-Kohmo, Kyoko; Fukuda, Yorihide; Matsuo, Koji; Fujii, Toshihito; Yasoda, Akihiro; Ogawa, Osamu; Inagaki, Nobuya

2018-03-01

Adrenal tumors are increasingly found incidentally during imaging examinations. It is important to distinguish pheochromocytomas from other adrenal tumors because of the risk of hypertensive crisis. Although catecholamines and their metabolites are generally used to diagnose pheochromocytoma, false-positive test results are common. An effective screening method to distinguish pheochromocytoma from adrenal incidentalomas is needed. We analyzed 297 consecutive patients with adrenal incidentalomas. Our findings included 162 non-functioning tumors, 47 aldosterone-producing adenomas, 26 metastases, 22 cases of subclinical Cushing's syndrome, 21 pheochromocytomas, 12 cases of Cushing's syndrome, and 7 adrenocortical cancers. We checked quantitative parameters such as age, blood, and urine catecholamines and their metabolites, neuron-specific enolase, size and computed tomography (CT) attenuation values. Among catecholamine-related parameters, the sum of urine metanephrine and normetanephrine (urineMNM) levels produced the highest area under the receiver operating characteristic curve regarding discrimination of pheochromocytoma from other lesions. Size and CT attenuation values also differed significantly. However, size was correlated with catecholamine levels. CT attenuation was not correlated with other factors. The optimal thresholds were 19 Hounsfield units (HU) for CT attenuation (sensitivity, 100%; specificity, 60%) and 0.43 mg/24 h for urineMNM (sensitivity, 89%; specificity, 96%). No pheochromocytomas were evident when CT attenuation values were under 19 HU. Even in adrenal tumors with CT attenuation values ≥ 19 HU, when urineMNM was < 0.43 mg/24 h, the frequency of pheochromocytoma was only 4.3%, when urineMNM was ≥ 0.43 mg/24 h, the frequency of pheochromocytoma was 93% and when urineMNM was > 0.77 mg/24 h the frequency of pheochromocytoma was 100%. CT attenuation value and urineMNM represented the most useful combination for diagnosis of pheochromocytoma.

SU-E-T-09: A Dosimetric Analysis of Various Clinically Used Bolus Materials

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stowe, M; Yeager, C; Zhou, F

Purpose: To evaluate the dosimetric effect of various clinically used bolus materials. Methods: Materials investigated include solid water, superflab, wet gauze, wet sheets, Play-Doh{sup ™}, and gauze embedded with petroleum jelly. Each bolusing material was scanned in a Philips CT to determine the Hounsfield unit (HU) and to verify uniformity throughout the material. Using the corresponding HU, boluses of 0.5 cm and 1.0 cm thicknesses were created in the Eclipse treatment planning system (TPS) on a solid water phantom. Dose was calculated at various depths for beam energies 6 MV, 6 MeV, 9 MeV, and 12 MeV to determine themore » effects of each material on deposition of dose. In addition, linac-based measurements at these energies were made using a farmer chamber in solid water. Wet sheets and wet gauze were measured with various water content to quantify the effects on dose. Results: Preliminary CT scans find a range in HU of bolus materials from −120 to almost 300. There is a trend in the dose at depth based on the HU of the material; however inconsistencies are found when the bolus materials have a negative HU value. The measured data indicates that there is a linear relationship between the mass of water in a material and the dose reading, the slope of which is material dependent. Conclusion: Due to the variation in HU of the bolus materials studied, it is recommended that any new bolus be evaluated before clinical use to determine physical and dosimetric properties. If possible, patients should have bolus included in their CT scans; or if the bolus is created in the TPS, the HU should correspond to the material used. For water-soaked materials, once the bolus material is selected (gauze or sheet), the bolusing effect is only dependent on the amount of water applied to the material.« less

Microdose computed tomographic cardiac angiography in normal cats.

PubMed

Rodriguez, Kiira T; O'Brien, Mauria A; Hartman, Susan K; Mulherin, Allison C; McReynolds, Casie J; McMichael, Maureen; Rapoport, Gregg; O'Brien, Robert T

2014-03-01

To determine if microdose contrast-enhanced multi-detector computed tomographic angiography (MDCTA) allows characterization of cardiac chambers in lightly sedated normal cats. Seven healthy domestic cats. Lightly sedated normal cats were imaged pre-contrast and with microdose (0.22 ml/kg of non-ionic iodinated contrast medium, 300 mg I/ml) triple-phase MDCTA in a motion restriction device. On pre-contrast images, the aorta (median: 52.43 Hounsfield units [HU], range 27.35-76.74 HU) was outlined by significantly (p = 0.015) lower attenuating periaortic fat (-66.16 HU, -42.62 to -92.77 HU). On post-contrast images, median peak contrast enhancement in the right ventricle (111.77 HU, 36.09-141.60 HU) was achieved in 3.1 s (range 2.9-7.3 s), in the aorta (149.30 HU, 99.43-319.60 HU) and left atrium (180.83 HU, 88.53-266.84 HU) in 6.4 s (range 5.6-7.7 s) and in the left ventricle (147.89 HU, 57.23-245.77 HU) in 7.10 s (range 6.2-11.2 s). Significantly higher attenuation was measured between all chambers and walls, the right ventricular lumen and interventricular septum (median ratio 53.78 HU, range 0.21-83.20 HU), left ventricular lumen and left ventricular free wall (89.32 HU, 38.81-185.95 HU) and aorta and periaortic fat (190.43 HU, 143.22-425.44 HU) on post-contrast images. Sufficient biological contrast is available on survey CT to discriminate between the aorta and the left atrium, and microdose MDCTA provides sufficient contrast enhancement for adequate visualization of the heart chambers in normal cats. Copyright © 2014 Elsevier B.V. All rights reserved.

Patient size and x-ray technique factors in head computed tomography examinations. I. Radiation doses.

PubMed

Huda, Walter; Lieberman, Kristin A; Chang, Jack; Roskopf, Marsha L

2004-03-01

We investigated how patient age, size and composition, together with the choice of x-ray technique factors, affect radiation doses in head computed tomography (CT) examinations. Head size dimensions, cross-sectional areas, and mean Hounsfield unit (HU) values were obtained from head CT images of 127 patients. For radiation dosimetry purposes patients were modeled as uniform cylinders of water. Dose computations were performed for 18 x 7 mm sections, scanned at a constant 340 mAs, for x-ray tube voltages ranging from 80 to 140 kV. Values of mean section dose, energy imparted, and effective dose were computed for patients ranging from the newborn to adults. There was a rapid growth of head size over the first two years, followed by a more modest increase of head size until the age of 18 or so. Newborns have a mean HU value of about 50 that monotonically increases with age over the first two decades of life. Average adult A-P and lateral dimensions were 186+/-8 mm and 147+/-8 mm, respectively, with an average HU value of 209+/-40. An infant head was found to be equivalent to a water cylinder with a radius of approximately 60 mm, whereas an adult head had an equivalent radius 50% greater. Adult males head dimensions are about 5% larger than for females, and their average x-ray attenuation is approximately 20 HU greater. For adult examinations performed at 120 kV, typical values were 32 mGy for the mean section dose, 105 mJ for the total energy imparted, and 0.64 mSv for the effective dose. Increasing the x-ray tube voltage from 80 to 140 kV increases patient doses by about a factor of 5. For the same technique factors, mean section doses in infants are 35% higher than in adults. Energy imparted for adults is 50% higher than for infants, but infant effective doses are four times higher than for adults. CT doses need to take into account patient age, head size, and composition as well as the selected x-ray technique factors.

Isolation, purification, crystallization, and preliminary X-ray diffraction study of the crystals of HU protein from M. gallisepticum

NASA Astrophysics Data System (ADS)

Nikolaeva, A. Yu.; Timofeev, V. I.; Boiko, K. M.; Korzhenevskii, D. A.; Rakitina, T. V.; Dorovatovskii, P. V.; Lipkin, A. V.

2015-11-01

HU proteins are involved in bacterial DNA and RNA repair. Since these proteins are absent in cells of higher organisms, inhibitors of HU proteins can be used as effective and safe antibiotics. The crystallization conditions for the M. gallisepticum HU protein were found and optimized by the vapor-diffusion method. The X-ray diffraction data set was collected to 2.91 Å resolution from the crystals grown by the vapor-diffusion method on a synchrotron source. The crystals of the HU protein belong to sp. gr. P41212 and have the following unit-cell parameters: a = b = 97.94 Å, c = 77.92 Å, α = β = γ = 90°.

Management Proposals of the Sabinas Reynosa Aquifer in Northeast Mexico, and Implications in the Development of Main Towns in Chihuahua

NASA Astrophysics Data System (ADS)

Sanchez, E. E.

2008-12-01

The Sabinas Reynosa water table aquifer is located in northeast Mexico in the state of Chihuahua, where this hydrologic unit is controlled by Laramide structures. The hydrostratigraphy consists of three units. At the base is a slightly compacted conglomerate HU1. The middle unit HU2 consists of clay materials packed with a carbonate cement. The upper unit is constituted by a sandy caliche with a calcareous matrix with secondary porosity, which allows it to store and transmit large volumes of water. The three units are of Paleogene age. Recently, the towns near the Sabinas Reynosa aquifer have presented supply problems, thus, this project will determine the hydrologic characterization using the groundwater budget method in order to establish the volume of water that the aquifer will yield per unit of time. The first phase consisted of defining the balance equation, by establishing the terms involved in the budget and calculating their respective values. Two different factors were defined: the inflows and outflows. In the first case, underground inflow with 225.68 Mm3 in the last five years, recharge by irrigation with 32.08 Mm3 and anthropogenic recharge with 270.50 Mm3 were considered. In the second case, the factors include underground outflow with 359.55 Mm3, pumping with 561.43 Mm3 and evapotranspiration from the water table with 130.61 Mm3. Although this last variable was calculated on a preliminary basis, a more accurate estimate requires additional studies (in process), with the aim of obtaining a more representative value. In this work is considered that evapotranspiration takes a decisive role in the analysis of the budget and hence, in the decisions that have to be taken for the proper management of the hydrological system.

Swabs as a tool for monitoring the presence of norovirus on environmental surfaces in the food industry.

PubMed

Rönnqvist, Maria; Rättö, Marjaana; Tuominen, Pirkko; Salo, Satu; Maunula, Leena

2013-08-01

Human norovirus (HuNoV), which causes gastroenteritis, can be transmitted to food and food contact surfaces via viruscontaminated hands. To investigate this transmission in food processing environments, we developed a swabbing protocol for environmental samples, evaluated the stability of HuNoV in the swabs, and applied the method in the food industry. Swabs made of polyester, flocked nylon, cotton wool, and microfiber were moistened in either phosphate-buffered saline (PBS) or glycine buffer (pH 9.5) and used to swab four surfaces (latex, plastic, stainless steel, and cucumber) inoculated with HuNoV. HuNoV was eluted with either PBS or glycine buffer and detected with quantitative reverse transcription PCR. HuNoV recoveries were generally higher with an inoculation dose of 100 PCR units than 1,000 PCR units. The highest recoveries were obtained when surfaces were swabbed with microfiber cloth moistened in and eluted with glycine buffer after a HuNoV inoculation dose of 100 PCR units: 66% ± 18% on latex, 89% ±2% on plastic, and 79% ±10% on stainless steel. The highest recovery for cucumber, 45% ±5%, was obtained when swabbing the surface with microfiber cloth and PBS. The stability of HuNoV was tested in microfiber cloths moistened in PBS or glycine buffer. HuNoV RNA was detected from swabs after 3 days at 4 and 22°C, although the RNA levels decreased more rapidly in swabs moistened with glycine buffer than in those moistened with PBS at 22°C. In the field study, 172 microfiber and 45 cotton wool swab samples were taken from environmental surfaces at three food processing companies. Five (5.6%) of 90 swabs collected in 2010 and 7 (8.5%) of 82 swabs collected in 2012 were positive for HuNoV genogroup II; all positive samples were collected with microfiber swabs. Three positive results were obtained from the production line and nine were obtained from the food workers' break room and restroom areas. Swabbing is a powerful tool for HuNoV RNA detection from environmental surfaces and enables investigation of virus transmission during food processing.

CRISPR Knockout of the HuR Gene Causes a Xenograft Lethal Phenotype.

PubMed

Lal, Shruti; Cheung, Edwin C; Zarei, Mahsa; Preet, Ranjan; Chand, Saswati N; Mambelli-Lisboa, Nicole C; Romeo, Carmella; Stout, Matthew C; Londin, Eric; Goetz, Austin; Lowder, Cinthya Y; Nevler, Avinoam; Yeo, Charles J; Campbell, Paul M; Winter, Jordan M; Dixon, Dan A; Brody, Jonathan R

2017-06-01

Pancreatic ductal adenocarcinoma (PDA) is the third leading cause of cancer-related deaths in the United States, whereas colorectal cancer is the third most common cancer. The RNA-binding protein HuR (ELAVL1) supports a pro-oncogenic network in gastrointestinal (GI) cancer cells through enhanced HuR expression. Using a publically available database, HuR expression levels were determined to be increased in primary PDA and colorectal cancer tumor cohorts as compared with normal pancreas and colon tissues, respectively. CRISPR/Cas9 technology was successfully used to delete the HuR gene in both PDA (MIA PaCa-2 and Hs 766T) and colorectal cancer (HCT116) cell lines. HuR deficiency has a mild phenotype, in vitro , as HuR-deficient MIA PaCa-2 (MIA.HuR-KO (-/-) ) cells had increased apoptosis when compared with isogenic wild-type (MIA.HuR-WT (+/+) ) cells. Using this isogenic system, mRNAs were identified that specifically bound to HuR and were required for transforming a two-dimensional culture into three dimensional (i.e., organoids). Importantly, HuR-deficient MIA PaCa-2 and Hs 766T cells were unable to engraft tumors in vivo compared with control HuR-proficient cells, demonstrating a unique xenograft lethal phenotype. Although not as a dramatic phenotype, CRISPR knockout HuR HCT116 colon cancer cells (HCT.HuR-KO (-/-) ) showed significantly reduced in vivo tumor growth compared with controls (HCT.HuR-WT (+/+) ). Finally, HuR deletion affects KRAS activity and controls a subset of pro-oncogenic genes. Implications: The work reported here supports the notion that targeting HuR is a promising therapeutic strategy to treat GI malignancies. Mol Cancer Res; 15(6); 696-707. ©2017 AACR . ©2017 American Association for Cancer Research.

Destruction of the Capsid and Genome of GII.4 Human Norovirus Occurs during Exposure to Metal Alloys Containing Copper

PubMed Central

Manuel, C. S.; Moore, M. D.

2015-01-01

Human norovirus (HuNoV) represents a significant public health burden worldwide and can be environmentally transmitted. Copper surfaces have been shown to inactivate the cultivable surrogate murine norovirus, but no such data exist for HuNoV. The purpose of this study was to characterize the destruction of GII.4 HuNoV and virus-like particles (VLPs) during exposure to copper alloy surfaces. Fecal suspensions positive for a GII.4 HuNoV outbreak strain or GII.4 VLPs were exposed to copper alloys or stainless steel for 0 to 240 min and recovered by elution. HuNoV genome integrity was assessed by reverse transcription-quantitative PCR (RT-qPCR) (without RNase treatment), and capsid integrity was assessed by RT-qPCR (with RNase treatment), transmission electron microscopy (TEM), SDS-PAGE/Western blot analysis, and a histo-blood group antigen (HBGA) binding assay. Exposure of fecal suspensions to pure copper for 60 min reduced the GII.4 HuNoV RNA copy number by ∼3 log10 units when analyzed by RT-qPCR without RNase treatment and by 4 log10 units when a prior RNase treatment was used. The rate of reduction of the HuNoV RNA copy number was approximately proportional to the percentage of copper in each alloy. Exposure of GII.4 HuNoV VLPs to pure-copper surfaces resulted in noticeable aggregation and destruction within 240 min, an 80% reduction in the VP1 major capsid protein band intensity in 15 min, and a near-complete loss of HBGA receptor binding within 8 min. In all experiments, HuNoV remained stable on stainless steel. These results suggest that copper surfaces destroy HuNoV and may be useful in preventing environmental transmission of the virus in at-risk settings. PMID:25979897

Ventilation-Perfusion Relationships Following Experimental Pulmonary Contusion

DTIC Science & Technology

2007-06-14

696.7 6.1 to 565.0 24.3 Hounsfield units ), as did VOL (4.3 0.5 to 33.5 3.2%). Multivariate linear regression of MGSD, VOL, VD/VT, and QS vs. PaO2...parenchyma was separated into four regions based on the Hounsfield unit (HU) ranges reported by Gattinoni et al. (23) via a segmentation process executed...determined by repeated measures ANOVA. CT, computed tomography; MGSD, mean gray-scale density of the entire lung by CT scan; HU, Hounsfield units

Effect of short-term recombinant human erythropoietin therapy in the prevention of anemia of prematurity in very low birth weight neonates.

PubMed

Yasmeen, B H N; Chowdhury, M A K A; Hoque, M M; Hossain, M M; Jahan, R; Akhtar, S

2012-12-01

Premature infants especially those with birth weight < 1500 g suffer from Anaemia of prematurity (AOP) and associated problems. Erythropoietin therapy is a safe effective way to prevent and to treat anaemia of prematurity. To evaluate the effect of short-term administration of recombinant human erythropoietin (rHuEPO) with iron and folic acid in very low birth weight (VLBW) neonates in the prevention of anaemia of prematurity. A randomized controlled trial was carried out at Dhaka Shishu Hospital. Sixty preterm very low birth weight (PTVLBW) babies were enrolled in this study. Thirty were assigned to rHuEPO group and 30 as control. Baseline haematologic values were estimated before administration of rHuEPO. From day 7 of life rHuEPO-200 IU/kg/dose subcutaneously every alternate day for 2 weeks was administered to rHuEPO group. All infants in both groups have received oral iron, folic acid from day 14. Clinical and haematological assessment was done at 6 and 10 weeks of life. Baseline clinical characteristics and haematologic values were almost similar in both groups. This study has shown increase in haematological values (haemoglobin and haematocrit) and reduction in the number of blood transfusions during both the 1st and 2nd follow up in rHuEPO group in comparison to control group (p < 0.01). Short-term rHuEPO appears to be very effective in prevention of Anaemia of prematurity.

SU-D-202-03: Statistical Segmentation On Quantitative CT for Assessing Spatial Tumor Response During Radiation Therapy Delivery

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schott, D; Chen, X; Klawikowski, S

2016-06-15

Purpose: Develop a method to segment regions of interest (ROIs) in tumor with statistically similar Hounsfield unit (HU) values and/or HU changes during chemoradiation therapy (CRT) delivery, to assess spatial tumor treatment response based on daily CTs during CRT delivery. Methods: Generate a three region map of ROIs with differential HUs, by sampling neighboring voxels around a selected voxel and comparing to the mean of the entire ROI using a t-test. The cumulative distribution function, P, is calculated from the t-test. The P value is assigned to be the value at the selected voxel, and this is repeated over allmore » voxels in the initial ROI. Three regions are defined as: (1-P) < 0.00001 (mid region), and 0.00001 < (1-P) (mean greater than baseline and mean lower than baseline). The test is then expanded to compare daily CT sets acquired during routine CT-guided RT delivery using a CT-on-rails. The first fraction CT is used as the baseline for comparison. We tested 15 pancreatic head tumor cases undergoing CRT, to identify the ROIs and changes corresponding to normal, fibrotic, and tumor tissue. The obtained ROIs were compared with MRI-ADC maps acquired pre- and post-CRT. Results: The ROIs in 13 out of 15 patients’ first fraction CTs and pre-CRT MRIs matched the general region and slices covered, as well as in 6 out of the 9 patients with post-CRT MRIs. The high HU region designated by the t-test was seen to correlate with the tumor region in MR, and these ROIs are positioned within the same region over the course of treatment. In patients with poorly delineated tumors in MR, the t-test was inconclusive. Conclusion: The proposed statistical segmentation technique shows the potential to identify regions in tumor with differential HUs and HU changes during CRT delivery for patients with pancreas head cancer.« less

Sixty-Four-Section Cardiac Computed Tomography in Mechanical Prosthetic Heart Valve Dysfunction: Thrombus or Pannus.

PubMed

Gündüz, Sabahattin; Özkan, Mehmet; Kalçik, Macit; Gürsoy, Ozan Mustafa; Astarcioğlu, Mehmet Ali; Karakoyun, Süleyman; Aykan, Ahmet Çağri; Biteker, Murat; Gökdeniz, Tayyar; Kaya, Hasan; Yesin, Mahmut; Duran, Nilüfer Ekşi; Sevinç, Deniz; Güneysu, Tahsin

2015-12-01

Distinguishing pannus and thrombus in patients with prosthetic valve dysfunction is essential for the selection of proper treatment. We have investigated the utility of 64-slice multidetector computed tomography (MDCT) in distinguishing between pannus and thrombus, the latter amenable to thrombolysis. Sixty-two (23 men, mean age 44±14 years) patients with suspected mechanical prosthetic valve dysfunction assessed by transesophageal echocardiography were included in this prospective observational trial. Subsequently, MDCT was performed before any treatment was started. Periprosthetic masses were detected by MDCT in 46 patients, and their attenuation values were measured as Hounsfield Units (HU). Patients underwent thrombolysis unless contraindicated, and those with a contraindication or failed thrombolysis underwent surgery. A mass which was completely lysed or surgically detected as a clot was classified as thrombus, whereas a mass which was surgically detected as tissue overgrowth was classified as pannus. A definitive diagnosis could be achieved in 37 patients with 39 MDCT masses (22 thrombus and 17 pannus). The mean attenuation value of 22 thrombotic masses was significantly lower than that in 17 pannus (87±59 versus 322±122; P<0.001). Area under the receiver operating characteristic curve was 0.96 (95% confidence interval: 0.91-0.99; P<0.001), and a cutoff point of HU≥145 provided high sensitivity (87.5%) and specificity (95.5%) in discriminating pannus from thrombus. Complete lysis was more common for masses with HU<90 compared with those with HU 90 to 145 (100% versus 42.1%; P=0.007). Sixty-four slice MDCT is helpful in identifying masses amenable to thrombolysis in patients with prosthetic valve dysfunction. A high (HU≥145) attenuation suggests pannus overgrowth, whereas a lower value is associated with thrombus formation. A higher attenuation (HU>90) is associated with reduced lysis rates. © 2015 American Heart Association, Inc.

Impact of stone density on outcomes in percutaneous nephrolithotomy (PCNL): an analysis of the clinical research office of the endourological society (CROES) pcnl global study database.

PubMed

Anastasiadis, Anastasios; Onal, Bulent; Modi, Pranjal; Turna, Burak; Duvdevani, Mordechai; Timoney, Anthony; Wolf, J Stuart; De La Rosette, Jean

2013-12-01

This study aimed to explore the relationship between stone density and outcomes of percutaneous nephrolithotomy (PCNL) using the Clinical Research Office of the Endourological Society (CROES) PCNL Global Study database. Patients undergoing PCNL treatment were assigned to a low stone density [LSD, ≤ 1000 Hounsfield units (HU)] or high stone density (HSD, > 1000 HU) group based on the radiological density of the primary renal stone. Preoperative characteristics and outcomes were compared in the two groups. Retreatment for residual stones was more frequent in the LSD group. The overall stone-free rate achieved was higher in the HSD group (79.3% vs 74.8%, p = 0.113). By univariate regression analysis, the probability of achieving a stone-free outcome peaked at approximately 1250 HU. Below or above this density resulted in lower treatment success, particularly at very low HU values. With increasing radiological stone density, operating time decreased to a minimum at approximately 1000 HU, then increased with further increase in stone density. Multivariate non-linear regression analysis showed a similar relationship between the probability of a stone-free outcome and stone density. Higher treatment success rates were found with low stone burden, pelvic stone location and use of pneumatic lithotripsy. Very low and high stone densities are associated with lower rates of treatment success and longer operating time in PCNL. Preoperative assessment of stone density may help in the selection of treatment modality for patients with renal stones.

Dose calculation accuracy of different image value to density tables for cone-beam CT planning in head & neck and pelvic localizations.

PubMed

Barateau, Anaïs; Garlopeau, Christopher; Cugny, Audrey; De Figueiredo, Bénédicte Henriques; Dupin, Charles; Caron, Jérôme; Antoine, Mikaël

2015-03-01

We aimed to identify the most accurate combination of phantom and protocol for image value to density table (IVDT) on volume-modulated arc therapy (VMAT) dose calculation based on kV-Cone-beam CT imaging, for head and neck (H&N) and pelvic localizations. Three phantoms (Catphan(®)600, CIRS(®)062M (inner phantom for head and outer phantom for body), and TomoTherapy(®) "Cheese" phantom) were used to create IVDT curves of CBCT systems with two different CBCT protocols (Standard-dose Head and Standard Pelvis). Hounsfield Unit (HU) time stability and repeatability for a single On-Board-Imager (OBI) and compatibility of two distinct devices were assessed with Catphan(®)600. Images from the anthropomorphic phantom CIRS ATOM(®) for both CT and CBCT modalities were used for VMAT dose calculation from different IVDT curves. Dosimetric indices from CT and CBCT imaging were compared. IVDT curves from CBCT images were highly different depending on phantom used (up to 1000 HU for high densities) and protocol applied (up to 200 HU for high densities). HU time stability was verified over seven weeks. A maximum difference of 3% on the dose calculation indices studied was found between CT and CBCT VMAT dose calculation across the two localizations using appropriate IVDT curves. One IVDT curve per localization can be established with a bi-monthly verification of IVDT-CBCT. The IVDT-CBCTCIRS-Head phantom with the Standard-dose Head protocol was the most accurate combination for dose calculation on H&N CBCT images. For pelvic localizations, the IVDT-CBCTCheese established with the Standard Pelvis protocol provided the best accuracy. Copyright © 2015 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

Dosimetric measurements of an n-butyl cyanoacrylate embolization material for arteriovenous malformations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Labby, Zacariah E., E-mail: zelabby@humonc.wisc.edu; Chaudhary, Neeraj; Gemmete, Joseph J.

2015-04-15

Purpose: The therapeutic regimen for cranial arteriovenous malformations often involves both stereotactic radiosurgery and endovascular embolization. Embolization agents may contain tantalum or other contrast agents to assist the neurointerventionalists, leading to concerns regarding the dosimetric effects of these agents. This study investigated dosimetric properties of n-butyl cyanoacrylate (n-BCA) plus lipiodol with and without tantalum powder. Methods: The embolization agents were provided cured from the manufacturer with and without added tantalum. Attenuation measurements were made for the samples and compared to the attenuation of a solid water substitute using a 6 MV photon beam. Effective linear attenuation coefficients (ELAC) were derivedmore » from attenuation measurements made using a portal imager and derived sample thickness maps projected in an identical geometry. Probable dosimetric errors for calculations in which the embolized regions are overridden with the properties of water were calculated using the ELAC values. Interface effects were investigated using a parallel plate ion chamber placed at set distances below fixed samples. Finally, Hounsfield units (HU) were measured using a stereotactic radiosurgery CT protocol, and more appropriate HU values were derived from the ELAC results and the CT scanner’s HU calibration curve. Results: The ELAC was 0.0516 ± 0.0063 cm{sup −1} and 0.0580 ± 0.0091 cm{sup −1} for n-BCA without and with tantalum, respectively, compared to 0.0487 ± 0.0009 cm{sup −1} for the water substitute. Dose calculations with the embolized region set to be water equivalent in the treatment planning system would result in errors of −0.29% and −0.93% per cm thickness of n-BCA without and with tantalum, respectively. Interface effects compared to water were small in magnitude and limited in distance for both embolization materials. CT values at 120 kVp were 2082 and 2358 HU for n-BCA without and with tantalum, respectively; dosimetrically appropriate HU values were estimated to be 79 and 199 HU, respectively. Conclusions: The dosimetric properties of the embolization agents are very close to those of water for a 6 MV beam. Therefore, treating the entire intracranial space as uniform in composition will result in less than 1% dosimetric error for n-BCA emboli smaller than 3.4 cm without added tantalum and n-BCA emboli smaller than 1.1 cm with added tantalum. Furthermore, when effective embolization can be achieved by the neurointerventionalist using n-BCA without tantalum, the dosimetric impact of overriding material properties will be lessened. However, due to the high attenuation of embolization agents with and without added tantalum for diagnostic energies, artifacts may occur that necessitate additional imaging to accurately identify the spatial extent of the region to be treated.« less

Work climate in Mexican hemodialysis units: a cross-sectional study.

PubMed

Rojas Russell, M; Tirado Gómez, L L; Pacheco Domínguez, R L; Escamilla Santiago, R; López Cervantes, M

2011-01-01

The work climate (WC) affects the performance of service providers and has an impact on the care provided to users. This is important in the case of conditions that affect the quality of life, as is the case of chronic kidney disease (CKD) treated with haemodialysis. In Mexico, the demand for the care of CKD cases is increasing and the haemodialysis offer is limited. The purpose of this study was to describe and compare the WC in public, private and social security haemodialysis units in Mexico and to validate a tool to measure WC in haemodialysis units (HU). 372 professionals from 84 HU in 27 states were interviewed using a questionnaire. This included questions about the WC, quality of care and structure and organisation of the HU. Variables were compared by type of institution and profession. Significant correlations were observed between the WC and indicators of the quality of care. Nine out of fourteen variables presented important differences by type of unit, with a better perception of WC in private units and a poorer perception in social security ones. The perception of WC relies on the organisation and planning of the institutions, as well as on their infrastructure. In the case of Social Security HU in Mexico, these appear to be the areas that require improvement in order to encourage a better work climate.

Assessment of the increased calcification of the jaw bone with CT-Scan after dental implant placement

PubMed Central

2011-01-01

Purpose This study was performed to evaluate the changes of jaw bone density around the dental implant after placement using computed tomography scan (CT-Scan). Materials and Methods This retrospective study consisted of 30 patients who had lost 1 posterior tooth in maxilla or mandible and installed dental implant. The patients took CT-Scan before and after implant placement. Hounsfield Unit (HU) was measured around the implants and evaluated the difference of HU before and after implant installation. Results The mean HU of jaw bone was 542.436 HU and 764.9 HU before and after implant placement, respectively (p<0.05). The means HUs for male were 632.3 HU and 932.2 HU and those for female 478.2 HU and 645.5 HU before and after implant placement, respectively (p<0.05). Also, the jaw bone with lower density needed longer period for implant procedure and the increased change of HU of jaw bone was less in the cases which needed longer period for osseointegration. Conclusion CT-Scan could be used to assess the change of bone density around dental implants. Bone density around dental implant was increased after placement. The increased rate of bone density could be determined by the quality of jaw bone before implant placement. PMID:21977476

Assessment of the increased calcification of the jaw bone with CT-Scan after dental implant placement.

PubMed

Yunus, Barunawaty

2011-06-01

This study was performed to evaluate the changes of jaw bone density around the dental implant after placement using computed tomography scan (CT-Scan). This retrospective study consisted of 30 patients who had lost 1 posterior tooth in maxilla or mandible and installed dental implant. The patients took CT-Scan before and after implant placement. Hounsfield Unit (HU) was measured around the implants and evaluated the difference of HU before and after implant installation. The mean HU of jaw bone was 542.436 HU and 764.9 HU before and after implant placement, respectively (p<0.05). The means HUs for male were 632.3 HU and 932.2 HU and those for female 478.2 HU and 645.5 HU before and after implant placement, respectively (p<0.05). Also, the jaw bone with lower density needed longer period for implant procedure and the increased change of HU of jaw bone was less in the cases which needed longer period for osseointegration. CT-Scan could be used to assess the change of bone density around dental implants. Bone density around dental implant was increased after placement. The increased rate of bone density could be determined by the quality of jaw bone before implant placement.

Evaluation of low-dose dual energy computed tomography for in vivo assessment of renal/ureteric calculus composition.

PubMed

Mahalingam, Harshavardhan; Lal, Anupam; Mandal, Arup K; Singh, Shrawan Kumar; Bhattacharyya, Shalmoli; Khandelwal, Niranjan

2015-08-01

This study aimed to assess the accuracy of low-dose dual-energy computed tomography (DECT) in predicting the composition of urinary calculi. A total of 52 patients with urinary calculi were scanned with a 128-slice dual-source DECT scanner by use of a low-dose protocol. Dual-energy (DE) ratio, weighted average Hounsfield unit (HU) of calculi, radiation dose, and image noise levels were recorded. Two radiologists independently rated study quality. Stone composition was assessed after extraction by Fourier transform infrared spectroscopy (FTIRS). Analysis of variance was used to determine if the differences in HU values and DE ratios between the various calculus groups were significant. Threshold cutoff values to classify the calculi into separate groups were identified by receiver operating characteristic curve analysis. A total of 137 calculi were detected. FTIRS analysis differentiated the calculi into five groups: uric acid (n=17), struvite (n=3), calcium oxalate monohydrate and dihydrate (COM-COD, n=84), calcium oxalate monohydrate (COM, n=28), and carbonate apatite (n=5). The HU value could differentiate only uric acid calculi from calcified calculi (p<0.001). The DE ratio could confidently differentiate uric acid, struvite, calcium oxalate, and carbonate apatite calculi (p<0.001) with cutoff values of 1.12, 1.34, and 1.66, respectively, giving >80% sensitivity and specificity to differentiate them. The DE ratio could not differentiate COM from COM-COD calculi. No study was rated poor in quality by either of the observers. The mean radiation dose was 1.8 mSv. Low-dose DECT accurately predicts urinary calculus composition in vivo while simultaneously reducing radiation exposure without compromising study quality.

Clinical Utility of Dual-Energy CT Analysis of Bone Marrow Edema in Acute Wrist Fractures.

PubMed

Ali, Ismail T; Wong, William D; Liang, Teresa; Khosa, Faisal; Mian, Memoona; Jalal, Sabeena; Nicolaou, Savvas

2018-04-01

The purpose of this study is to determine the utility of dual-energy CT (DECT) for assessing carpal fractures and to obtain an attenuation value cutoff (in Hounsfield units) to identify bone marrow edema due to an acute carpal fracture. In this retrospective study, 24 patients who presented with wrist fractures from September 3, 2014, through March 9, 2015, underwent imaging with DECT (80 and 140 kVp). Using the three-material decomposition algorithm specific for virtual noncalcium to construct images, two radiologists identified carpal fractures and associated bone marrow edema. Readers noted the attenuation at areas with and without bone marrow edema. The cutoff value was obtained by ROC analysis and was internally validated on 13 separate patients with suspected wrist fractures. A p < 0.05 was considered statistically significant. CT attenuation was significantly higher in areas of bone marrow edema than in areas without it (p < 0.0001, t test). A cutoff of 5.90 HU allows detection of bone marrow edema associated with acute wrist fractures with 100% sensitivity and 99.5% specificity, compared with visual DECT interpretation. In the 13 validation cases, the cutoff of 5.90 HU identified bone marrow edema with 100% accuracy, compared with visual interpretation. Kappa values were 0.83 between the two readings by reader 1, and 0.73 and 0.96 comparing the two readings of reader 1 with the reading by reader 2. DECT is a useful tool for identifying bone marrow edema in the setting of acute wrist fractures, providing an alternative to MRI. A cutoff value of 5.90 HU can be used for accurate diagnosis and exclusion of carpal fractures.

Evaluation of low-dose dual energy computed tomography for in vivo assessment of renal/ureteric calculus composition

PubMed Central

Mahalingam, Harshavardhan; Mandal, Arup K; Singh, Shrawan Kumar; Bhattacharyya, Shalmoli; Khandelwal, Niranjan

2015-01-01

Purpose This study aimed to assess the accuracy of low-dose dual-energy computed tomography (DECT) in predicting the composition of urinary calculi. Materials and Methods A total of 52 patients with urinary calculi were scanned with a 128-slice dual-source DECT scanner by use of a low-dose protocol. Dual-energy (DE) ratio, weighted average Hounsfield unit (HU) of calculi, radiation dose, and image noise levels were recorded. Two radiologists independently rated study quality. Stone composition was assessed after extraction by Fourier transform infrared spectroscopy (FTIRS). Analysis of variance was used to determine if the differences in HU values and DE ratios between the various calculus groups were significant. Threshold cutoff values to classify the calculi into separate groups were identified by receiver operating characteristic curve analysis. Results A total of 137 calculi were detected. FTIRS analysis differentiated the calculi into five groups: uric acid (n=17), struvite (n=3), calcium oxalate monohydrate and dihydrate (COM-COD, n=84), calcium oxalate monohydrate (COM, n=28), and carbonate apatite (n=5). The HU value could differentiate only uric acid calculi from calcified calculi (p<0.001). The DE ratio could confidently differentiate uric acid, struvite, calcium oxalate, and carbonate apatite calculi (p<0.001) with cutoff values of 1.12, 1.34, and 1.66, respectively, giving >80% sensitivity and specificity to differentiate them. The DE ratio could not differentiate COM from COM-COD calculi. No study was rated poor in quality by either of the observers. The mean radiation dose was 1.8 mSv. Conclusions Low-dose DECT accurately predicts urinary calculus composition in vivo while simultaneously reducing radiation exposure without compromising study quality. PMID:26279828

Tillage practices in the conterminous United States, 1989-2004-Datasets Aggregated by Watershed

USGS Publications Warehouse

Baker, Nancy T.

2011-01-01

This report documents the methods used to aggregate county-level tillage practices to the 8-digit hydrologic unit (HU) watershed. The original county-level data were collected by the Conservation Technology Information Center (CTIC). The CTIC collects tillage data by conducting surveys about tillage systems for all counties in the United States. Tillage systems include three types of conservation tillage (no-till, ridge-till, and mulch-till), reduced tillage, and intensive tillage. Total planted acreage for each tillage practice for each crop grown is reported to the CTIC. The dataset includes total planted acreage by tillage type for selected crops (corn, cotton, grain sorghum, soybeans, fallow, forage, newly established permanent pasture, spring and fall seeded small grains, and 'other' crops) for 1989-2004. Two tabular datasets, based on the 1992 enhanced and 2001 National Land Cover Data (NLCD), are provided as part of this report and include the land-cover area-weighted interpolation and aggregation of acreage for each tillage practice in each 8-digit HU watershed in the conterminous United States for each crop. Watershed aggregations were done by overlying the 8-digit HU polygons with a raster of county boundaries and a raster of either the enhanced 1992 or the 2001 NLCD for cultivated land to derive a county/land-cover area weighting factor. The weighting factor then was applied to the county-level tillage data for the counties within each 8-digit HU and summed to yield the total acreage of each tillage type within each 8-digit HU watershed.

Use of CT Hounsfield unit density to identify ablated tumor after laparoscopic radiofrequency ablation of hepatic tumors.

PubMed

Berber, E; Foroutani, A; Garland, A M; Rogers, S J; Engle, K L; Ryan, T L; Siperstein, A E

2000-09-01

When attempting to interpret CT scans after radiofrequency thermal ablation (RFA) of liver tumors, it is sometimes difficult to distinguish ablated from viable tumor tissue. Identification of the two types of tissue is specially problematic for lesions that are hypodense before ablation. The aim of this study was to determine whether quantitative Hounsfield unit (HU) density measurements can be used to document the lack of tumor perfusion and thereby identify ablated tissue. Liver spiral CT scans of 13 patients with 51 lesions undergoing laparoscopic RFA for metastatic liver tumors within a 2-year time period were reviewed. HU density of the lesions as well as normal liver were measured pre- and postoperatively in each CT phase (noncontrast, arterial, portovenous). Statistical analyses were performed using Student's paired t-test and ANOVA. Normal liver parenchyma, which was used as a control, showed a similar increase with contrast injection in both pre- and postprocedure CT scans (56.4 +/- 2.4 vs 57.1 +/- 2.4 HU, respectively; p = 0.3). In contrast, ablated liver lesions showed a preablation increase of 45.7 +/- 3.4 HU but only a minimal postablation increase of 6.6 +/- 0.7 HU (p < 0.0001). This was true for highly vascular tumors (neuroendocrine) as well as hypovascular ones (adenocarcinoma). This is the first study to define quantitative radiological criteria using HU density for the evaluation of ablated tissues. A lack of increase in HU density with contrast injection indicates necrotic tissue, whereas perfused tissue shows an increase in HU density. This technique can be used in the evaluation of patients undergoing RFA.

The synthetic cannabinoid HU210 induces spatial memory deficits and suppresses hippocampal firing rate in rats.

PubMed

Robinson, L; Goonawardena, A V; Pertwee, R G; Hampson, R E; Riedel, G

2007-07-01

Previous work implied that the hippocampal cannabinoid system was particularly important in some forms of learning, but direct evidence for this hypothesis is scarce. We therefore assessed the effects of the synthetic cannabinoid HU210 on memory and hippocampal activity. HU210 (100 microg kg(-1)) was administered intraperitoneally to rats under three experimental conditions. One group of animals were pre-trained in spatial working memory using a delayed-matching-to-position task and effects of HU210 were assessed in a within-subject design. In another, rats were injected before acquisition learning of a spatial reference memory task with constant platform location. Finally, a separate group of animals was implanted with electrode bundles in CA1 and CA3 and single unit responses were isolated, before and after HU210 treatment. HU210 treatment had no effect on working or short-term memory. Relative to its control Tween 80, deficits in acquisition of a reference memory version of the water maze were obtained, along with drug-related effects on anxiety, motor activity and spatial learning. Deficits were not reversed by the CB(1) receptor antagonists SR141716A (3 mg kg(-1)) or AM281 (1.5 mg kg(-1)). Single unit recordings from principal neurons in hippocampal CA3 and CA1 confirmed HU210-induced attenuation of the overall firing activity lowering both the number of complex spikes fired and the occurrence of bursts. These data provide the first direct evidence that the underlying mechanism for the spatial memory deficits induced by HU210 in rats is the accompanying abnormality in hippocampal cell firing.

Quantitative CT characterization of pediatric lung development using routine clinical imaging

PubMed Central

Stein, Jill M.; Walkup, Laura L.; Brody, Alan S.; Fleck, Robert J.

2016-01-01

Background The use of quantitative CT analysis in children is limited by lack of normal values of lung parenchymal attenuation. These characteristics are important because normal lung development yields significant parenchymal attenuation changes as children age. Objective To perform quantitative characterization of normal pediatric lung parenchymal X-ray CT attenuation under routine clinical conditions in order to establish a baseline comparison to that seen in pathological lung conditions. Materials and methods We conducted a retrospective query of normal CT chest examinations in children ages 0–7 years from 2004 to 2014 using standard clinical protocol. During these examinations semi-automated lung parenchymal segmentation was performed to measure lung volume and mean lung attenuation. Results We analyzed 42 CT examinations in 39 children, ages 3 days to 83 months (mean ± standard deviation [SD] = 42±27 months). Lung volume ranged 0.10–1.72 liters (L). Mean lung attenuation was much higher in children younger than 12 months, with values as high as −380 Hounsfield units (HU) in neonates (lung volume 0.10 L). Lung volume decreased to approximately −650 HU by age 2 years (lung volume 0.47 L), with subsequently slower exponential decrease toward a relatively constant value of −860 HU as age and lung volume increased. Conclusion Normal lung parenchymal X-ray CT attenuation decreases with increasing lung volume and age; lung attenuation decreases rapidly in the first 2 years of age and more slowly thereafter. This change in normal lung attenuation should be taken into account as quantitative CT methods are translated to pediatric pulmonary imaging. PMID:27576458

Combination of super chilling and high carbon dioxide concentration techniques most effectively to preserve freshness of shell eggs during long-term storage.

PubMed

Yanagisawa, T; Ariizumi, M; Shigematsu, Y; Kobayashi, H; Hasegawa, M; Watanabe, K

2010-01-01

This study was made to examine the combined effects of stored temperature and carbon dioxide atmosphere on shell egg quality. The shell eggs were packed into polyethylene terephthalate/polyethylene (PET/PE) pouches and stored at 0 degrees C (super chilling), 10 degrees C, and 20 degrees C, respectively for 90 d. The atmospheric carbon dioxide concentration was controlled to obtain the 3 concentration levels of high (about 2.0%), medium (about 0.5%), and low (below 0.01%). Changes in Haugh unit (HU) values, weakening of vitelline membranes, and generation of volatiles were analyzed to evaluate the freshness of shell eggs. Results showed that, compared with the other combinations, the technique of super chilling and high carbon dioxide concentration enabled shell eggs to be most effectively stored for 90 d, based on estimations of the statistical significances of differences in HU values, and on maintaining the initial HU values during storage. In addition, the storage of shell eggs using this combination technique was found to significantly prevent the weakening of the vitelline membrane based on the estimations of numbers of eggs without vitelline membrane breakage when eggs broke, and significantly lowered the incidence of hexanal in the yolk from exposure to the gas chromatographic-mass spectrometric analyses of volatiles. Thus, these results confirmed that the combination of super chilling and high carbon dioxide concentration was the most effective technique for preserving shell eggs during a long term of 90 d compared with other combination techniques.

Technical Note: Radiation properties of tissue- and water-equivalent materials formulated using the stoichiometric analysis method in charged particle therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yohannes, Indra; Vasiliniuc, Stefan; Hild, Sebastian

Purpose: Five tissue- and water-equivalent materials (TEMs) mimicking ICRU real tissues have been formulated using a previously established stoichiometric analysis method (SAM) to be applied in charged particle therapy. The purpose of this study was an experimental verification of the TEMs-SAM against charged particle beam measurements and for different computed tomography (CT) scanners. The potential of the TEMs-SAM to be employed in the dosimetry was also investigated. Methods: Experimental verification with three CT scanners was carried out to validate the calculated Hounsfield units (HUs) of the TEMs. Water-equivalent path lengths (WEPLs) of the TEMs for proton (106.8 MeV/u), helium (107.93more » MeV/u), and carbon (200.3 MeV/u) ions were measured to be compared with the computed relative stopping powers. HU calibration curves were also generated. Results: Differences between the measured HUs of the TEMs and the calculated HUs of the ICRU real tissues for all CT scanners were smaller than 4 HU except for the skeletal tissues which deviated up to 21 HU. The measured WEPLs verified the calculated WEPLs of the TEMs (maximum deviation was 0.17 mm) and were in good agreement with the calculated WEPLs of the ICRU real tissues (maximum deviation was 0.23 mm). Moreover, the relative stopping powers converted from the measured WEPLs differed less than 0.8% and 1.3% from the calculated values of the SAM and the ICRU, respectively. Regarding the relative nonelastic cross section per unit of volume for 200 MeV protons, the ICRU real tissues were generally well represented by the TEMs except for adipose which differed 3.8%. Further, the HU calibration curves yielded the mean and the standard deviation of the errors not larger than 0.5% and 1.9%, respectively. Conclusions: The results of this investigation implied the potential of the TEMs formulated using the SAM to be employed for both, beam dosimetry and HU calibration in charged particle therapy.« less

Post-mortem CT: Hounsfield unit profiles obtained in the lungs with respect to the cause of death assessment.

PubMed

Schober, Daniel; Schwendener, Nicole; Zech, Wolf-Dieter; Jackowski, Christian

2017-01-01

Segmentation of the lungs using post-mortem computed tomography (PMCT) data was so far not feasible due to post-mortem changes such as internal livores. Recently, an Osirix plug-in has been developed allowing automatically segmenting lungs also in PMCT data. The aim of this study was to investigate if the Hounsfield unit (HU) profiles obtained in PMCT data of the segmented lung tissue present with specific behaviour in relation to the cause of death. In 105 PMCT data sets of forensic cases, the entire lung volumes were segmented using the Mia Lite plug-in on Osirix. HU profiles of the lungs were generated and correlated to cause of death groups as assessed after forensic autopsy (cardiac death, fatal haemorrhage, craniocerebral injury, intoxication, drowning, hypothermia, hanging and suffocation). Especially cardiac death cases, intoxication cases, fatal haemorrhage cases and hypothermia cases showed very specific HU profiles. In drowning, the profiles showed two different behaviours representing wet and dry drowning. HU profiles rather varied in craniocerebral injury cases, hanging cases as well as in suffocation cases. HU profiles of the lungs segmented from PMCT data may support the cause of death diagnosis as they represent specific morphological changes in the lungs such as oedema, congestion or blood loss. Especially in cardiac death, intoxication, fatal haemorrhage, hypothermia and drowning cases, HU profiles may be very supportive for the forensic pathologist.

Pre-exposure Prophylaxis With OspA-Specific Human Monoclonal Antibodies Protects Mice Against Tick Transmission of Lyme Disease Spirochetes.

PubMed

Wang, Yang; Kern, Aurélie; Boatright, Naomi K; Schiller, Zachary A; Sadowski, Andrew; Ejemel, Monir; Souders, Colby A; Reimann, Keith A; Hu, Linden; Thomas, William D; Klempner, Mark S

2016-07-15

Tick transmission of Borrelia spirochetes to humans results in significant morbidity from Lyme disease worldwide. Serum concentrations of antibodies against outer surface protein A (OspA) were shown to correlate with protection from infection with Borrelia burgdorferi, the primary cause of Lyme disease in the United States. Mice transgenic for human immunoglobulin genes were immunized with OspA from B. burgdorferi to generate human monoclonal antibodies (HuMabs) against OspA. HuMabs were generated and tested in in vitro borreliacidal assays and animal protection assays. Nearly 100 unique OspA-specific HuMabs were generated, and 4 HuMabs (221-7, 857-2, 319-44, and 212-55) were selected as lead candidates on the basis of borreliacidal activity. HuMabs 319-44, 857-2, and 212-55 were borreliacidal against 1 or 2 Borrelia genospecies, whereas 221-7 was borreliacidal (half maximal inhibitory concentration, < 1 nM) against B. burgdorferi, Borrelia afzelii, and Borrelia garinii, the 3 main genospecies endemic in the United States, Europe, and Asia. All 4 HuMabs completely protected mice from infection at 10 mg/kg in a murine model of tick-mediated transmission of B. burgdorferi  Our study indicates that OspA-specific HuMabs can prevent the transmission of Borrelia and that administration of these antibodies could be employed as preexposure prophylaxis for Lyme disease. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

Feasibility of Selective Catheter-Directed Coronary Computed Tomography Angiography Using Ultralow-Dose Intracoronary Contrast Injection in a Swine Model.

PubMed

Hong, Youngtaek; Shin, Sanghoon; Park, Hyung-Bok; Lee, Byoung Kwon; Arsanjani, Reza; ó Hartaigh, Bríain; Ha, Seongmin; Jang, Yeonggul; Jeon, Byunghwan; Jung, Sunghee; Park, Se-Il; Sung, Ji Min; Shim, Hackjoon; Chang, Hyuk-Jae

2015-07-01

Selective catheter-directed intracoronary contrast injected coronary computed tomography angiography (selective CCTA) has recently been introduced for on-site evaluation of coronary artery disease during coronary artery catheterization. In this study, we aimed to develop a feasible protocol for selective CCTA using ultralow-dose contrast medium as compared with conventional intravenous CCTA (IV CCTA). A novel combined system incorporating coronary angiography and a 320-detector row computed tomographic scanner was used to study 4 swine (35-40 kg) under animal institutional review board approval. A selective CCTA scan was simultaneously performed with an injection of 13.13 mgI/mL of modulated contrast medium at multiple different injection rates including 2, 3, and 4 mL/s and different total injection volumes of either 20 or 30 mL. Intravenous CCTA was performed with 60 mL of contrast medium, followed by 30 mL of saline chaser at 5 mL/s. Coronary mean and peak intensity, transluminal attenuation gradient, as well as 3-dimensional maximum intensity projections were obtained. Attenuation values (mean ± standard error, in Hounsfield units [HUs]) of selective CCTA for the left anterior descending (LAD) and right coronary artery (RCA) using the various combinations of injection rates and total injection volumes were as follows: 20 mL at 2 mL/s (LAD, 270.3 ± 20.4 HU; RCA, 322.6 ± 7.4 HU), 20 mL at 3 mL/s (LAD, 262.9 ± 20.4 HU; RCA, 264.7 ± 7.4 HU), 30 mL at 3 mL/s (LAD, 276.8 ± 20.4 HU; RCA, 274.0 ± 7.4 HU), 20 mL at 4 mL/s (LAD, 268.0 ± 20.4 HU; RCA, 277.7 ± 7.4 HU), and 30 mL at 4 mL/s (LAD, 251.3 ± 20.4 HU; RCA, 334.7 ± 7.4 HU). The representative protocol of the selective CCTA studies produced results within the optimal enhancement range (approximately 250-350 HU) for all segments, and comparison of transluminal attenuation gradient data with selective CCTA and IV CCTA studies demonstrated that the former method was more homogenous (-1.5245 and -1.7558 for LAD as well as 0.0459 and 0.0799 for RCA, respectively). Notably, the volume of iodine contrast medium used for selective CCTA was reported to be 1.09% (0.2 g) of IV CCTA (24 g). The current findings demonstrate the feasibility of selective CCTA using ultralow-dose intracoronary contrast injection. This technique may provide additional means of coronary evaluation in patients who may require strategic planning before a procedure using a combined modality system.

Image quality and absorbed dose comparison of single- and dual-source cone-beam computed tomography.

PubMed

Miura, Hideharu; Ozawa, Shuichi; Okazue, Toshiya; Kawakubo, Atsushi; Yamada, Kiyoshi; Nagata, Yasushi

2018-05-01

Dual-source cone-beam computed tomography (DCBCT) is currently available in the Vero4DRT image-guided radiotherapy system. We evaluated the image quality and absorbed dose for DCBCT and compared the values with those for single-source CBCT (SCBCT). Image uniformity, Hounsfield unit (HU) linearity, image contrast, and spatial resolution were evaluated using a Catphan phantom. The rotation angle for acquiring SCBCT and DCBCT images is 215° and 115°, respectively. The image uniformity was calculated using measurements obtained at the center and four peripheral positions. The HUs of seven materials inserted into the phantom were measured to evaluate HU linearity and image contrast. The Catphan phantom was scanned with a conventional CT scanner to measure the reference HU for each material. The spatial resolution was calculated using high-resolution pattern modules. Image quality was analyzed using ImageJ software ver. 1.49. The absorbed dose was measured using a 0.6-cm 3 ionization chamber with a 16-cm-diameter cylindrical phantom, at the center and four peripheral positions of the phantom, and calculated using weighted cone-beam CT dose index (CBCTDI w ). Compared with that of SCBCT, the image uniformity of DCBCT was slightly reduced. A strong linear correlation existed between the measured HU for DCBCT and the reference HU, although the linear regression slope was different from that of the reference HU. DCBCT had poorer image contrast than did SCBCT, particularly with a high-contrast material. There was no significant difference between the spatial resolutions of SCBCT and DCBCT. The absorbed dose for DCBCT was higher than that for SCBCT, because in DCBCT, the two x-ray projections overlap between 45° and 70°. We found that the image quality was poorer and the absorbed dose was higher for DCBCT than for SCBCT in the Vero4DRT. © 2018 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.

Visceral and Subcutaneous Fat Quality is Associated with Cardiometabolic Risk

PubMed Central

Rosenquist, Klara J.; Pedley, Alison; Massaro, Joseph M.; Therkelsen, Kate E.; Murabito, Joanne M.; Hoffmann, Udo; Fox, Caroline S.

2013-01-01

Objective The aim of this study was to evaluate whether computed tomography (CT) attenuation, as a measure of fat quality, is associated with cardiometabolic risk factors above and beyond fat quantity. Background Visceral (VAT) and subcutaneous adipose tissue (SAT) are pathogenic fat depots associated with cardiometabolic risk. Adipose tissue attenuation in CT images is variable, similar to adipose tissue volume. However, whether the quality of abdominal fat attenuation is associated to cardiometabolic risk independent of the quantity is uncertain. Methods Participants were drawn from the Framingham Heart Study CT sub-study. VAT and SAT volumes were acquired by semi-quantitative assessment. Fat quality was measured by CT attenuation and recorded as mean Hounsfield Units (HU) within each fat depot. Sex-specific linear and logistic multivariable regression models were used to assess the association between standard deviation (SD) decrease in HU and each risk factor. Results Lower CT attenuation of VAT and SAT was correlated with higher BMI levels in both sexes. Risk factors were generally more adverse with decreasing HU values. For example, in women, per 1-SD decrease in VAT HU, the odds ratio (OR) was increased for hypertension (OR 1.80), impaired fasting glucose (OR 2.10), metabolic syndrome (OR 3.65) and insulin resistance (OR 3.36) (all p<0.0001). In models that further adjusted for VAT volume, impaired fasting glucose, metabolic syndrome and insulin resistance remained significant. Trends were similar but less pronounced in SAT and in men. There was evidence of an interaction between HU and fat volume among both women and men. Conclusion Lower CT attenuation of VAT and SAT is associated with adverse cardiometabolic risk above and beyond total adipose tissue volume. Qualitative indices of abdominal fat depots may provide insight regarding cardiometabolic risk independent of fat quantity. PMID:23664720

Quantification of image contrast of infarcts on computed tomography scans.

PubMed

Gomolka, R S; Chrzan, R M; Urbanik, A; Kazmierski, R; Grzanka, A D; Nowinski, W L

2017-02-01

Introduction Accurate identification of infarcts in non-contrast computed tomography (NC-CT) scans of the brain is fundamental in the diagnosis and management of patients with stroke. Quantification of image contrast properties at the boundaries of ischemic infarct regions in NC-CT can contribute to a more precise manual or automatic delineation of these regions. Here we explore these properties quantitatively. Methods We retrospectively investigated 519 NC-CT studies of 425 patients with clinically confirmed ischemic strokes. The average and standard deviation (SD) of patients' age was 67.5 ± 12.4 years and the average(median)±SD time from symptoms onset to NC-CT examination was 27.4(12)±35.7 h. For every scan with an ischemic lesion identified by experts, the image contrast of the lesion vs. normal surrounding parenchyma was calculated as a difference of mean Hounsfield Unit (HU) of 1-5 consecutive voxels (the contrast window width) belonging to the lesion and to the parenchyma. This contrast was calculated at each single voxel of ischemic lesion boundaries (previously delineated by the experts) in horizontal and vertical directions in each image. The distributions of obtained horizontal, vertical and both contrasts combined were calculated among all 519 NC-CTs. Results The highest applicative contrast window width was identified as 5 voxels. The ischemic infarcts were found to be characterized by 6.60 HU, 8.28 HU and 7.55 HU mean values for distributions of horizontal, vertical and combined contrasts. Approximately 40-50% of the infarct boundary voxels were found to refer to the image contrast below 5 HU. Conclusion Low image contrast of ischemic lesions prevents accurate delineation of the infarcts in NC-CT.

MRI-Based Computed Tomography Metal Artifact Correction Method for Improving Proton Range Calculation Accuracy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Park, Peter C.; Schreibmann, Eduard; Roper, Justin

2015-03-15

Purpose: Computed tomography (CT) artifacts can severely degrade dose calculation accuracy in proton therapy. Prompted by the recently increased popularity of magnetic resonance imaging (MRI) in the radiation therapy clinic, we developed an MRI-based CT artifact correction method for improving the accuracy of proton range calculations. Methods and Materials: The proposed method replaces corrupted CT data by mapping CT Hounsfield units (HU number) from a nearby artifact-free slice, using a coregistered MRI. MRI and CT volumetric images were registered with use of 3-dimensional (3D) deformable image registration (DIR). The registration was fine-tuned on a slice-by-slice basis by using 2D DIR.more » Based on the intensity of paired MRI pixel values and HU from an artifact-free slice, we performed a comprehensive analysis to predict the correct HU for the corrupted region. For a proof-of-concept validation, metal artifacts were simulated on a reference data set. Proton range was calculated using reference, artifactual, and corrected images to quantify the reduction in proton range error. The correction method was applied to 4 unique clinical cases. Results: The correction method resulted in substantial artifact reduction, both quantitatively and qualitatively. On respective simulated brain and head and neck CT images, the mean error was reduced from 495 and 370 HU to 108 and 92 HU after correction. Correspondingly, the absolute mean proton range errors of 2.4 cm and 1.7 cm were reduced to less than 2 mm in both cases. Conclusions: Our MRI-based CT artifact correction method can improve CT image quality and proton range calculation accuracy for patients with severe CT artifacts.« less

Absolute Hounsfield unit measurement on noncontrast computed tomography cannot accurately predict struvite stone composition.

PubMed

Marchini, Giovanni Scala; Gebreselassie, Surafel; Liu, Xiaobo; Pynadath, Cindy; Snyder, Grace; Monga, Manoj

2013-02-01

The purpose of our study was to determine, in vivo, whether single-energy noncontrast computed tomography (NCCT) can accurately predict the presence/percentage of struvite stone composition. We retrospectively searched for all patients with struvite components on stone composition analysis between January 2008 and March 2012. Inclusion criteria were NCCT prior to stone analysis and stone size ≥4 mm. A single urologist, blinded to stone composition, reviewed all NCCT to acquire stone location, dimensions, and Hounsfield unit (HU). HU density (HUD) was calculated by dividing mean HU by the stone's largest transverse diameter. Stone analysis was performed via Fourier transform infrared spectrometry. Independent sample Student's t-test and analysis of variance (ANOVA) were used to compare HU/HUD among groups. Spearman's correlation test was used to determine the correlation between HU and stone size and also HU/HUD to % of each component within the stone. Significance was considered if p<0.05. Fourty-four patients met the inclusion criteria. Struvite was the most prevalent component with mean percentage of 50.1%±17.7%. Mean HU and HUD were 820.2±357.9 and 67.5±54.9, respectively. Struvite component analysis revealed a nonsignificant positive correlation with HU (R=0.017; p=0.912) and negative with HUD (R=-0.20; p=0.898). Overall, 3 (6.8%) had <20% of struvite component; 11 (25%), 25 (56.8%), and 5 (11.4%) had 21% to 40%, 41% to 60%, and 61% to 80% of struvite, respectively. ANOVA revealed no difference among groups regarding HU (p=0.68) and HUD (p=0.37), with important overlaps. When comparing pure struvite stones (n=5) with other miscellaneous stones (n=39), no difference was found for HU (p=0.09) but HUD was significantly lower for pure stones (27.9±23.6 v 72.5±55.9, respectively; p=0.006). Again, significant overlaps were seen. Pure struvite stones have significantly lower HUD than mixed struvite stones, but overlap exists. A low HUD may increase the suspicion for a pure struvite calculus.

In Search of Golden Rules: Comment on Hypothesis-Testing Approaches to Setting Cutoff Values for Fit Indexes and Dangers in Overgeneralizing Hu and Bentler's (1999) Findings

ERIC Educational Resources Information Center

Marsh, Herbert W.; Hau, Kit-Tai; Wen, Zhonglin

2004-01-01

Goodness-of-fit (GOF) indexes provide "rules of thumb"?recommended cutoff values for assessing fit in structural equation modeling. Hu and Bentler (1999) proposed a more rigorous approach to evaluating decision rules based on GOF indexes and, on this basis, proposed new and more stringent cutoff values for many indexes. This article discusses…

A dual model HU conversion from MRI intensity values within and outside of bone segment for MRI-based radiotherapy treatment planning of prostate cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Korhonen, Juha, E-mail: juha.p.korhonen@hus.fi; Department of Oncology, Helsinki University Central Hospital, POB-180, 00029 HUS; Kapanen, Mika

2014-01-15

Purpose: The lack of electron density information in magnetic resonance images (MRI) poses a major challenge for MRI-based radiotherapy treatment planning (RTP). In this study the authors convert MRI intensity values into Hounsfield units (HUs) in the male pelvis and thus enable accurate MRI-based RTP for prostate cancer patients with varying tissue anatomy and body fat contents. Methods: T{sub 1}/T{sub 2}*-weighted MRI intensity values and standard computed tomography (CT) image HUs in the male pelvis were analyzed using image data of 10 prostate cancer patients. The collected data were utilized to generate a dual model HU conversion technique from MRImore » intensity values of the single image set separately within and outside of contoured pelvic bones. Within the bone segment local MRI intensity values were converted to HUs by applying a second-order polynomial model. This model was tuned for each patient by two patient-specific adjustments: MR signal normalization to correct shifts in absolute intensity level and application of a cutoff value to accurately represent low density bony tissue HUs. For soft tissues, such as fat and muscle, located outside of the bone contours, a threshold-based segmentation method without requirements for any patient-specific adjustments was introduced to convert MRI intensity values into HUs. The dual model HU conversion technique was implemented by constructing pseudo-CT images for 10 other prostate cancer patients. The feasibility of these images for RTP was evaluated by comparing HUs in the generated pseudo-CT images with those in standard CT images, and by determining deviations in MRI-based dose distributions compared to those in CT images with 7-field intensity modulated radiation therapy (IMRT) with the anisotropic analytical algorithm and 360° volumetric-modulated arc therapy (VMAT) with the Voxel Monte Carlo algorithm. Results: The average HU differences between the constructed pseudo-CT images and standard CT images of each test patient ranged from −2 to 5 HUs and from 22 to 78 HUs in soft and bony tissues, respectively. The average local absolute value differences were 11 HUs in soft tissues and 99 HUs in bones. The planning target volume doses (volumes 95%, 50%, 5%) in the pseudo-CT images were within 0.8% compared to those in CT images in all of the 20 treatment plans. The average deviation was 0.3%. With all the test patients over 94% (IMRT) and 92% (VMAT) of dose points within body (lower than 10% of maximum dose suppressed) passed the 1 mm and 1% 2D gamma index criterion. The statistical tests (t- and F-tests) showed significantly improved (p ≤ 0.05) HU and dose calculation accuracies with the soft tissue conversion method instead of homogeneous representation of these tissues in MRI-based RTP images. Conclusions: This study indicates that it is possible to construct high quality pseudo-CT images by converting the intensity values of a single MRI series into HUs in the male pelvis, and to use these images for accurate MRI-based prostate RTP dose calculations.« less

Measuring coronary calcium on CT images adjusted for attenuation differences.

PubMed

Nelson, Jennifer Clark; Kronmal, Richard A; Carr, J Jeffrey; McNitt-Gray, Michael F; Wong, Nathan D; Loria, Catherine M; Goldin, Jonathan G; Williams, O Dale; Detrano, Robert

2005-05-01

To quantify scanner and participant variability in attenuation values for computed tomographic (CT) images assessed for coronary calcium and define a method for standardizing attenuation values and calibrating calcium measurements. Institutional review board approval and participant informed consent were obtained at all study sites. An image attenuation adjustment method involving the use of available calibration phantom data to define standard attenuation values was developed. The method was applied to images from two population-based multicenter studies: the Coronary Artery Risk Development in Young Adults study (3041 participants) and the Multi-Ethnic Study of Atherosclerosis (6814 participants). To quantify the variability in attenuation, analysis of variance techniques were used to compare the CT numbers of standardized torso phantom regions across study sites, and multivariate linear regression models of participant-specific calibration phantom attenuation values that included participant age, race, sex, body mass index (BMI), smoking status, and site as covariates were developed. To assess the effect of the calibration method on calcium measurements, Pearson correlation coefficients between unadjusted and attenuation-adjusted calcium measurements were computed. Multivariate models were used to examine the effect of sex, race, BMI, smoking status, unadjusted score, and site on Agatston score adjustments. Mean attenuation values (CT numbers) of a standard calibration phantom scanned beneath participants varied significantly according to scanner and participant BMI (P < .001 for both). Values were lowest for Siemens multi-detector row CT scanners (110.0 HU), followed by GE-Imatron electron-beam (116.0 HU) and GE LightSpeed multi-detector row scanners (121.5 HU). Values were also lower for morbidly obese (BMI, > or =40.0 kg/m(2)) participants (108.9 HU), followed by obese (BMI, 30.0-39.9 kg/m(2)) (114.8 HU), overweight (BMI, 25.0-29.9 kg/m(2)) (118.5 HU), and normal-weight or underweight (BMI, <25.0 kg/m(2)) (120.1 HU) participants. Agatston score calibration adjustments ranged from -650 to 1071 (mean, -8 +/- 50 [standard deviation]) and increased with Agatston score (P < .001). The direction and magnitude of adjustment varied significantly according to scanner and BMI (P < .001 for both) and were consistent with phantom attenuation results in that calibration resulted in score decreases for images with higher phantom attenuation values. Image attenuation values vary by scanner and participant body size, producing calcium score differences that are not due to true calcium burden disparities. Use of calibration phantoms to adjust attenuation values and calibrate calcium measurements in research studies and clinical practice may improve the comparability of such measurements between persons scanned with different scanners and within persons over time.

Deriving concentrations of oxygen and carbon in human tissues using single- and dual-energy CT for ion therapy applications

NASA Astrophysics Data System (ADS)

Landry, Guillaume; Parodi, Katia; Wildberger, Joachim E.; Verhaegen, Frank

2013-08-01

Dedicated methods of in-vivo verification of ion treatment based on the detection of secondary emitted radiation, such as positron-emission-tomography and prompt gamma detection require high accuracy in the assignment of the elemental composition. This especially concerns the content in carbon and oxygen, which are the most abundant elements of human tissue. The standard single-energy computed tomography (SECT) approach to carbon and oxygen concentration determination has been shown to introduce significant discrepancies in the carbon and oxygen content of tissues. We propose a dual-energy CT (DECT)-based approach for carbon and oxygen content assignment and investigate the accuracy gains of the method. SECT and DECT Hounsfield units (HU) were calculated using the stoichiometric calibration procedure for a comprehensive set of human tissues. Fit parameters for the stoichiometric calibration were obtained from phantom scans. Gaussian distributions with standard deviations equal to those derived from phantom scans were subsequently generated for each tissue for several values of the computed tomography dose index (CTDIvol). The assignment of %weight carbon and oxygen (%wC,%wO) was performed based on SECT and DECT. The SECT scheme employed a HU versus %wC,O approach while for DECT we explored a Zeff versus %wC,O approach and a (Zeff, ρe) space approach. The accuracy of each scheme was estimated by calculating the root mean square (RMS) error on %wC,O derived from the input Gaussian distribution of HU for each tissue and also for the noiseless case as a limiting case. The (Zeff, ρe) space approach was also compared to SECT by comparing RMS error for hydrogen and nitrogen (%wH,%wN). Systematic shifts were applied to the tissue HU distributions to assess the robustness of the method against systematic uncertainties in the stoichiometric calibration procedure. In the absence of noise the (Zeff, ρe) space approach showed more accurate %wC,O assignment (largest error of 2%) than the Zeff versus %wC,O and HU versus %wC,O approaches (largest errors of 15% and 30%, respectively). When noise was present, the accuracy of the (Zeff, ρe) space (DECT approach) was decreased but the RMS error over all tissues was lower than the HU versus %wC,O (SECT approach) (5.8%wC versus 7.5%wC at CTDIvol = 20 mGy). The DECT approach showed decreasing RMS error with decreasing image noise (or increasing CTDIvol). At CTDIvol = 80 mGy the RMS error over all tissues was 3.7% for DECT and 6.2% for SECT approaches. However, systematic shifts greater than ±5HU undermined the accuracy gains afforded by DECT at any dose level. DECT provides more accurate %wC,O assignment than SECT when imaging noise and systematic uncertainties in HU values are not considered. The presence of imaging noise degrades the DECT accuracy on %wC,O assignment but it remains superior to SECT. However, DECT was found to be sensitive to systematic shifts of human tissue HU.

Application of a Receptor-Binding Capture Quantitative Reverse Transcription-PCR Assay To Concentrate Human Norovirus from Sewage and To Study the Distribution and Stability of the Virus

PubMed Central

Yang, David; Pan, Liangwen; Mandrell, Robert

2012-01-01

Water is an important route for human norovirus (HuNoV) transmission. Using magnetic beads conjugated with blood group-like antigens (HuNoV receptors), we developed a simple and rapid receptor-binding capture and magnetic sequestration (RBCMS) method and compared it to the existing negatively charged membrane absorption/elution (NCMAE) method for concentrating HuNoV from sewage effluent. RBCMS required 6-fold-less sample volume than the NCMAE method and also resulted in a significantly higher yield of HuNoV. The NCMAE and RBCMS concentrations of genogroup I (GI) HuNoV measured by quantitative reverse transcription-PCR (qRT-PCR) resulted in average threshold cycle (CT) values of 34.68 (8.68 copies, 252-fold concentration) versus 34.07 (13.05 copies, 477-fold concentration), respectively; the NCMAE and RBCMS concentrations of genogroup II (GII) HuNoV were measured as average CT values of 33.32 (24.7 copies, 239-fold concentration) versus 32.38 (46.9 copies, 333-fold concentration), respectively. The specificity of qRT-PCR was confirmed by traditional RT-PCR and an RNase I protection assay. The qRT-PCR signal from RBCMS-concentrated HuNoV treated with RNase I indicated that it was from encapsidated RNA and, probably, viable virus. In contrast, the qRT-PCR signal from NCMAE-concentrated HuNoV was not protected from RNase I and, likely, degradation. Both GI and GII HuNoV were detected from sewage effluent samples collected between April and July with average concentrations of 7.8 × 103 genomic copies per liter (gc/liter) and 4.3 × 104 gc/liter, respectively. No GI and <2% GII HuNoV were detected in sewage samples stored at room temperature for 4 weeks. We conclude that RBCMS requires less sample volume, has better recovery and sensitivity, and is faster than NCMAE for detection of HuNoV in sewage. PMID:22101044

Impact of Computer-Aided CT and PET Analysis on Non-invasive T Staging in Patients with Lung Cancer and Atelectasis.

PubMed

Flechsig, Paul; Rastgoo, Ramin; Kratochwil, Clemens; Martin, Ole; Holland-Letz, Tim; Harms, Alexander; Kauczor, Hans-Ulrich; Haberkorn, Uwe; Giesel, Frederik L

2018-04-20

Tumor delineation within an atelectasis in lung cancer patients is not always accurate. When T staging is done by integrated 2-deoxy-2-[ 18 F]fluoro-D-glucose ([ 18 F]FDG)-positron emission tomography (PET)/X-ray computer tomography (CT), tumors of neuroendocrine differentiation and slowly growing tumors can present with reduced FDG uptake, thus aggravating an exact T staging. In order to further exhaust information derived from [ 18 F]FDG-PET/CT, we evaluated the impact of CT density and maximum standardized uptake value (SUVmax) for the classification of different tumor subtypes within a surrounding atelectasis, as well as possible cutoff values for the differentiation between the primary tumor and atelectatic lung tissue. Seventy-two patients with histologically proven lung cancer and adjacent atelectasis were investigated. Non-contrast-enhanced [ 18 F]FDG-PET/CT was performed within 2 weeks before surgery/biopsy. Boundaries of the primary within the atelectasis were determined visually on the basis of [ 18 F]FDG uptake; CT density was quantified manually within each primary and each atelectasis. CT density of the primary (36.4 Hounsfield units (HU) ± 6.2) was significantly higher compared to that of atelectatic lung (24.3 HU ± 8.3; p < 0.01), irrespective of the histological subtype. The discrimination between different malignant tumors using density analysis failed. SUVmax was increased in squamous cell carcinomas compared to adenocarcinomas. Irrespective of the malignant subtype, a possible cutoff value of 24 HU may help to exclude the presence of a primary in lesions below 24 HU, whereas a density above a threshold of 40 HU can help to exclude atelectatic lung. Density measurements in patients with lung cancer and surrounding atelectasis may help to delineate the primary tumor, irrespective of the specific lung cancer subtype. This could improve T staging and radiation treatment planning (RTP) without additional application of a contrast agent in CT, or an additional magnetic resonance imaging (MRI), even in cases of lung tumors of neuroendocrine differentiation or in slowly growing tumors with less avidity to [ 18 F]FDG.

Trapping volumetric measurement by multidetector CT in chronic obstructive pulmonary disease: Effect of CT threshold

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Xiaohua; Yuan, Huishu; Duan, Jianghui

2013-08-15

Purpose: The purpose of this study was to evaluate the effect of various computed tomography (CT) thresholds on trapping volumetric measurements by multidetector CT in chronic obstructive pulmonary disease (COPD).Methods: Twenty-three COPD patients were scanned with a 64-slice CT scanner in both the inspiratory and expiratory phase. CT thresholds of −950 Hu in inspiration and −950 to −890 Hu in expiration were used, after which trapping volumetric measurements were made using computer software. Trapping volume percentage (Vtrap%) under the different CT thresholds in the expiratory phase and below −950 Hu in the inspiratory phase was compared and correlated with lungmore » function.Results: Mean Vtrap% was similar under −930 Hu in the expiratory phase and below −950 Hu in the inspiratory phase, being 13.18 ± 9.66 and 13.95 ± 6.72 (both lungs), respectively; this difference was not significant (P= 0.240). Vtrap% under −950 Hu in the inspiratory phase and below the −950 to −890 Hu threshold in the expiratory phase was moderately negatively correlated with the ratio of forced expiratory volume in one second to forced vital capacity and the measured value of forced expiratory volume in one second as a percentage of the predicted value.Conclusions: Trapping volumetric measurement with multidetector CT is a promising method for the quantification of COPD. It is important to know the effect of various CT thresholds on trapping volumetric measurements.« less

Enhanced Androgen Signaling with Androgen Receptor Overexpression in the Osteoblast Lineage Controls Skeletal Turnover, Matrix Quality and Bone Architecture

DTIC Science & Technology

2008-12-01

Hounsfield units (HU) to mineral values (mg/cc of HA) through the use of...Ph.D. Russell Turner 5e. TASK NUMBER E-Mail: wirenk@ohsu.edu 5f. WORK UNIT NUMBER 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) 8...gn al in g IL -6 S ig n al in g H ep at ic Fi b ro si s/ H ep at ic … IL -1 0 S ig n al in g V D R /R X R A ct iv at io n P PA R S ig n al

WE-FG-207B-10: Dual-Energy CT Monochromatic Image Consistency Across Vendors and Platforms

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jacobsen, M; Wood, C; Cody, D

Purpose: Although dual-energy CT provides improved sensitivity of HU for certain tissue types at lower simulated energy levels, if these values vary by scanner type they may impact clinical patient management decisions. Each manufacturer has selected a specific dual-energy CT approach (or in one case, three different approaches); understanding HU variability among low monochromatic images may be required when more than one dual-energy CT scanner type is available for use. Methods: A large elliptical dualenergy quality control phantom (Gammex Inc.; Middleton, WI) containing several standard tissue type materials was scanned at least three times on each of the following systems:more » GE HD750, prototype GE Revolution CT with GSI, Siemens Flash, Siemens Edge, Siemens AS 128, and Philips IQon. Images were generated at 50, 70, and 140 keV. Soft tissue and Iodine HU were measured on a single central 5mm-thick image; NIST constants were used to calculate the ideal HU for each material. Scan acquisitions were approximately dose-matched (∼25mGy CTDIvol) and image parameters were held as consistent as possible (thickness, kernel, no noise reduction). Results: Measured soft tissue (29 HU at 120 kVp) varied from 28 HU to 44 HU at 50 keV (excluding one outlier), from 21 HU to 31 HU at 70 keV, and from 19 HU to 32 HU at 140 keV. Measured iodine (5mg/ml, 106 HU at 120 kVp) varied from 246 HU to 280 HU at 50 keV, from 123 HU to 129 HU at 70 keV, and from 22 HU to 32 HU at 140 keV. Conclusion: Measured HU in standard rods across 3 dual-energy CT manufacturers and 6 scanner models varied directly with monochromatic level, with the most variability was observed at 50 keV and least variability at 70keV. Future work will include additional scanner platforms and how measurement variability impacts radiologists. This research has been supported by funds from Dr. William Murphy, Jr., the John S. Dunn, Sr. Distinguished Chair in Diagnostic Imaging at MD Anderson Cancer Center.« less

Analysis of deep inferior epigastric perforator (DIEP) arteries by using MDCTA: Comparison between 2 post-processing techniques.

PubMed

Saba, Luca; Atzeni, Matteo; Ribuffo, Diego; Mallarini, Giorgio; Suri, Jasjit S

2012-08-01

Our purpose was to compare two post-processing techniques, Maximum-Intensity-Projection (MIP) and Volume Rendering (VR) for the study of perforator arteries. Thirty patients who underwent Multi-Detector-Row CT Angiography (MDCTA) between February 2010 and May 2010 were retrospectively analyzed. For each patient and for each reconstruction method, the image quality was evaluated and the inter- and intra-observer agreement was calculated according to the Cohen statistics. The Hounsfield Unit (HU) value in the common femoral artery was quantified and the correlation (Pearson Statistic) between image quality and HU value was explored. The Pearson r between the right and left common femoral artery was excellent (r=0.955). The highest image quality score was obtained using MIP for both observers (total value 75, with a mean value 2.67 for observer 1 and total value of 79 and a mean value of 2.82 for observer 2). The highest agreement between the two observers was detected using the MIP protocol with a Cohen kappa value of 0.856. The ROC area under the curve (Az) for the VR is 0.786 (0.086 SD; p value=0.0009) whereas the ROC area under the curve (Az) for the MIP is 0.0928 (0.051 SD; p value=0.0001). MIP showed the optimal inter- and intra-observer agreement and the highest quality scores and therefore should be used as post-processing techniques in the analysis of perforating arteries. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

SU-D-206-05: A Critical Look at CBCT-Based Dose Calculation Accuracy as It Is Applied to Adaptive Radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bejarano Buele, A; Sperling, N; Parsai, E

2016-06-15

Purpose: Cone-beam CTs (CBCT) obtained from On-Board Imaging Devices (OBI) are increasingly being used for dose calculation purposes in adaptive radiotherapy. Patient and target morphology are monitored and the treatment plan is updated using CBCT. Due to the difference in image acquisition parameters, dose calculated in a CBCT can differ from planned dose. We evaluate the difference between dose calculation in kV CBCT and simulation CT, and the effect of HU-density tables in dose discrepancies Methods: HU values for various materials were obtained using a Catphan 504 phantom for a simulator CT (CTSIM) and two different OBI systems using threemore » imaging protocols: Head, Thorax and Pelvis. HU-density tables were created in the TPS for each OBI image protocol. Treatment plans were made on each Catphan 504 dataset and on the head, thorax and pelvis sections of an anthropomorphic phantom, with and without the respective HU-density table. DVH information was compared among OBI systems and planning CT. Results: Dose calculations carried on the Catphan 504 CBCTs, with and without the respective CT-density table, had a maximum difference of −0.65% from the values on the planning CT. The use of the respective HU-density table decreased the percent differences from planned values by half in most of the protocols. For the anthropomorphic phantom datasets, the use of the correct HU-density table reduced differences by 0.89% on OBI1 and 0.59% on OBI2 for the head, 0.49% on OBI1 for the thorax, and 0.25% on OBI2 for the pelvis. Differences from planned values without HU-density correction ranged from 3.13% (OBI1, thorax) to 0.30% (OBI2, thorax). Conclusion: CT-density tables in the TPS yield acceptable differences when used in partly homogeneous medium. Further corrections are needed when the medium contains pronounced density differences for accurate CBCT calculation. Current difference range (1–3%) can be clinically acceptable.« less

Effect of egg freshness on texture and baking characteristics of batter systems formulated using egg, flour and sugar.

PubMed

Xing, Liting; Niu, Fuge; Su, Yujie; Yang, Yanjun

2016-04-01

The aim of this work was to evaluate the effects of egg freshness on baking properties and final qualities in batter systems. Batters were made with eggs of different freshness, and the properties of batter systems were studied through rheological analysis, rapid viscosity analysis (RVA), differential scanning calorimetry (DSC), batter density and expansion rate during the baking and cooling processes. Moreover, the qualities of final baked systems were investigated, including specific volume and texture profile analysis (TPA). The flow behavior of batters showed that the consistency index (K) decreased as the Haugh unit (HU) value decreased, while the flow behavior index (n) increased. Both the storage modulus (G') and loss modulus (G″) determined by mechanical spectra at 20 °C decreased with decreasing HU. RVA and DSC determinations revealed that lower-HU samples had a lower viscosity in the baking process and a shorter time for starch gelatinization and egg protein denaturation. Observation of the batter density revealed an increasing change, which was reflected by a decrease in the specific volume of final models. TPA showed significant differences in hardness and chewiness, but no significant differences in springiness and cohesiveness were found. The egg freshness affected the properties of batter systems. © 2015 Society of Chemical Industry.

A relative quantitative assessment of myocardial perfusion by first-pass technique: animal study

NASA Astrophysics Data System (ADS)

Chen, Jun; Zhang, Zhang; Yu, Xuefang; Zhou, Kenneth J.

2015-03-01

The purpose of this study is to quantitatively assess the myocardial perfusion by first-pass technique in swine model. Numerous techniques based on the analysis of Computed Tomography (CT) Hounsfield Unit (HU) density have emerged. Although these methods proposed to be able to assess haemodynamically significant coronary artery stenosis, their limitations are noticed. There are still needs to develop some new techniques. Experiments were performed upon five (5) closed-chest swine. Balloon catheters were placed into the coronary artery to simulate different degrees of luminal stenosis. Myocardial Blood Flow (MBF) was measured using color microsphere technique. Fractional Flow Reserve (FFR) was measured using pressure wire. CT examinations were performed twice during First-pass phase under adenosine-stress condition. CT HU Density (HUDCT) and CT HU Density Ratio (HUDRCT) were calculated using the acquired CT images. Our study presents that HUDRCT shows a good (y=0.07245+0.09963x, r2=0.898) correlation with MBF and FFR. In receiver operating characteristic (ROC) curve analyses, HUDRCT provides excellent diagnostic performance for the detection of significant ischemia during adenosine-stress as defined by FFR indicated by the value of Area Under the Curve (AUC) of 0.927. HUDRCT has the potential to be developed as a useful indicator of quantitative assessment of myocardial perfusion.

Evaluation of individually body weight adapted contrast media injection in coronary CT-angiography.

PubMed

Mihl, Casper; Kok, Madeleine; Altintas, Sibel; Kietselaer, Bas L J H; Turek, Jakub; Wildberger, Joachim E; Das, Marco

2016-04-01

Contrast media (CM) injection protocols should be customized to the individual patient. Aim of this study was to determine if software tailored CM injections result in diagnostic enhancement of the coronary arteries in computed tomography angiography (CTA) and if attenuation values were comparable between different weight categories. 265 consecutive patients referred for routine coronary CTA were scanned on a 2nd generation dual-source CT. Group 1 (n=141) received an individual CM bolus based on weight categories (39-59 kg; 60-74 kg; 75-94 kg; 95-109 kg) and scan duration ('high-pitch: 1s; "dual-step prospective triggering": 7s), as determined by contrast injection software (Certegra™ P3T, Bayer, Berlin, Germany). Group 2 (n=124) received a standard fixed CM bolus; Iopromide 300 mgI/ml; volume: 75 ml; flow rate: 7.2 ml/s. Contrast enhancement was measured in all proximal and distal coronary segments. Subjective and objective image quality was evaluated. Statistical analysis was performed using SPSS (IBM, version 20.0). For group 1, mean attenuation values of all segments were diagnostic (>325 HU) without statistical significant differences between different weight categories (p>0.17), proximal vs. distal: 449 ± 65-373 ± 58 HU (39-59 kg); 443 ± 69-367 ± 81 HU (60-74 kg); 427 ± 59-370 ± 61 HU (75-94 kg); 427 ± 73-347 ± 61 HU (95-109 kg). Mean CM volumes were: 55 ± 6 ml (39-59 kg); 61 ± 7 ml (60-74 kg); 71 ± 8 ml (75-94 kg); 84 ± 9 ml (95-109 kg). For group 2, mean attenuation values were not all diagnostic with differences between weight categories (p<0.01), proximal vs. distal: 611 ± 142-408 ± 69 HU (39-59 kg); 562 ± 135-389 ± 98 HU (60-74 kg); 481 ± 83-329 ± 81 HU (75-94 kg); 420 ± 73-305 ± 35 HU (95-109 kg). Comparable image noise and image quality were found between groups (p ≥ 0.330). Individually tailored CM injection protocols yield diagnostic attenuation and a more homogeneous enhancement pattern between different weight groups. CM volumes could be reduced for the majority of patients utilizing individualized CM bolus application. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

TH-CD-207B-11: Multi-Vendor Phantom Study of CT Lung Density Metrics: Is a Reproducibility of Less Than 1 HU Achievable?

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen-Mayer, H; Judy, P; Fain, S

Purpose: To standardize the calibration procedures of CT lung density measurements using low-density reference foams in a phantom, and to demonstrate a reproducibility of less than 1 HU for lung equivalent foam densities measured across CT vendor platforms and protocols. Methods: A phantom study was conducted on CT scanner models from 4 vendors at 100, 120, and 135/140 kVp and 1.5, 3, and 6 mGy dose settings, using a lung density phantom containing air, water, and 3 reference foams (indirectly calibrated) with discrete densities simulating a 5-cm slice of the human chest. Customized segmentation software was used to analyze themore » images and generate a mean HU and variance for each of the density for the 22 vendor/protocols. A 3-step calibration process was devised to remove a scanner-dependent parameter using linear regression of the HU value vs the relative electron density. The results were mapped to a single energy (80 keV) for final comparison. Results: The heterogeneity across vendor platforms for each density assessed by a random effects model was reduced by 50% after re-calibration, while the standard deviation of the mean HU values also improved by about the same amount. The 95% CI of the final HU value was within +/−1 HU for all 3 reference foam densities. For the backing lung foam in the phantom (served as an “unknown”), this CI is +/− 1.6 HU. The kVp and dose settings did not appear to have significant contributions to the variability. Conclusion: With the proposed calibration procedures, the inter-scanner reproducibility of better than 1 HU is demonstrated in the current phantom study for the reference foam densities, but not yet achieved for a test density. The sources of error are being investigated in the next round of scanning with a certified Standard Reference Material for direct calibration. Fain: research funding from GE Healthcare to develop pulmonary MRI techniques. Hoppel: employee of Toshiba Medical Research Institute USA/financial interest with GE Healthcare. M. Fuld: employee of Siemens Healthcare for medical device equipment and software. This project is supported partially by RSNA QIBA Concept Award (Fain), NIH/NIBIB, HHSN268201300071C (Y).« less

Comparison between two treatment protocols with recombinant human erythropoietin (rHuEpo) in the treatment of late anemia in neonates with Rh-isoimmunization.

PubMed

Zuppa, A A; Alighieri, G; Fracchiolla, A; Catenazzi, P; D'Antuono, A; Riccardi, R; Cavani, M; Romagnoli, C

2012-01-01

[corrected] The Rh-hemolytic disease can lead to a late anemia by hemolytic and hyporigenerative mechanism. We compared the effectiveness of rHuEPO in two care protocols that differ for doses of rHuEPO administrated and for timing of administration. A cohort of 14 neonates was investigated. The neonates were treated with two different protocols. Protocol A: a dose of 200 U/kg/day of rHuEpo administered subcutaneously starting from the end of the second week of life; Protocol B: a dose of 400 U/kg/day of rHuEpo administered subcutaneously starting from the end of the first week of life. The hematocrit values in the protocol A group decreased during treatment (32,5% vs 25,2%), whereas the hematocrit value in protocol B group remained almost stable (38,7% vs 42,8%). The mean numbers of platelets remained stable in both groups while neutrophils increased in protocol A group and decreased in protocol B (p<0,05). Reticulocyte count increased during treatment in both groups, although only in protocol B group it was statistically significative (p<0,05). Our results suggest a similar efficacy between the two treatment protocols. Increasing doses of rHuEPO do not seem enhancing their effectiveness and the incidence of side effects.

Cloning, expression, purification and preliminary crystallographic studies of the adenylate/uridylate-rich element-binding protein HuR complexed with its target RNA

PubMed Central

Iyaguchi, Daisuke; Yao, Min; Tanaka, Isao; Toyota, Eiko

2009-01-01

Adenylate/uridylate-rich elements (AREs), which are found in the 3′-untrans­lated region (UTR) of many mRNAs, influence the stability of cytoplasmic mRNA. HuR (human antigen R) binds to AREs and regulates various genes. In order to reveal the RNA-recognition mechanism of HuR protein, an RNA-binding region of human HuR containing two N-terminal RNA-recognition motif domains bound to an 11-­base RNA fragment has been crystallized. The crystals belonged to space group P212121, with unit-cell parameters a = 42.4, b = 44.9, c = 91.1 Å. X-­ray diffraction data were collected to 1.8 Å resolution. PMID:19255485

Low contrast media volume in pre-TAVI CT examinations.

PubMed

Kok, Madeleine; Turek, Jakub; Mihl, Casper; Reinartz, Sebastian D; Gohmann, Robin F; Nijssen, Estelle C; Kats, Suzanne; van Ommen, Vincent G; Kietselaer, Bas L J H; Wildberger, Joachim E; Das, Marco

2016-08-01

To evaluate image quality using reduced contrast media (CM) volume in pre-TAVI assessment. Forty-seven consecutive patients referred for pre-TAVI examination were evaluated. Patients were divided into two groups: group 1 BMI < 28 kg/m(2) (n = 29); and group 2 BMI > 28 kg/m(2) (n = 18). Patients received a combined scan protocol: retrospective ECG-gated helical CTA of the aortic root (80kVp) followed by a high-pitch spiral CTA (group 1: 70 kV; group 2: 80 kVp) from aortic arch to femoral arteries. All patients received one bolus of CM (300 mgI/ml): group 1: volume = 40 ml; flow rate = 3 ml/s, group 2: volume = 53 ml; flow rate = 4 ml/s. Attenuation values (HU) and contrast-to-noise ratio (CNR) were measured at the levels of the aortic root (helical) and peripheral arteries (high-pitch). Diagnostic image quality was considered sufficient at attenuation values > 250HU and CNR > 10. Diagnostic image quality for TAVI measurements was obtained in 46 patients. Mean attenuation values and CNR (HU ± SD) at the aortic root (helical) were: group 1: 381 ± 65HU and 13 ± 8; group 2: 442 ± 68HU and 10 ± 5. At the peripheral arteries (high-pitch), mean values were: group 1: 430 ± 117HU and 11 ± 6; group 2: 389 ± 102HU and 13 ± 6. CM volume can be substantially reduced using low kVp protocols, while maintaining sufficient image quality for the evaluation of aortic root and peripheral access sites. • Image quality could be maintained using low kVp scan protocols. • Low kVp protocols reduce contrast media volume by 34-67 %. • Less contrast media volume lowers the risk of contrast-induced nephropathy.

Three-dimensional segmentation of the tumor mass in computed tomographic images of neuroblastoma

NASA Astrophysics Data System (ADS)

Deglint, Hanford J.; Rangayyan, Rangaraj M.; Boag, Graham S.

2004-05-01

Tumor definition and diagnosis require the analysis of the spatial distribution and Hounsfield unit (HU) values of voxels in computed tomography (CT) images, coupled with a knowledge of normal anatomy. Segmentation of the tumor in neuroblastoma is complicated by the fact that the mass is almost always heterogeneous in nature; furthermore, viable tumor, necrosis, fibrosis, and normal tissue are often intermixed. Rather than attempt to separate these tissue types into distinct regions, we propose to explore methods to delineate the normal structures expected in abdominal CT images, remove them from further consideration, and examine the remaining parts of the images for the tumor mass. We explore the use of fuzzy connectivity for this purpose. Expert knowledge provided by the radiologist in the form of the expected structures and their shapes, HU values, and radiological characteristics are also incorporated in the segmentation algorithm. Segmentation and analysis of the tissue composition of the tumor can assist in quantitative assessment of the response to chemotherapy and in the planning of delayed surgery for resection of the tumor. The performance of the algorithm is evaluated using cases acquired from the Alberta Children's Hospital.

Single energy micro CT SkyScan 1173 for the characterization of urinary stone

NASA Astrophysics Data System (ADS)

Fitri, L. A.; Asyana, V.; Ridwan, T.; Anwary, F.; Soekersi, H.; Latief, F. D. E.; Haryanto, F.

2016-08-01

A urinary stone is a solid piece of material produced from crystallization of excreted substances in the urine. Knowledge of the composition of urinary stones is essential to determine the suitable treatment for the patient. The aim of this research was to characterize urinary stones using single energy micro CT SkyScan 1173. Six human urinary stones were scanned in vitro using 80 kV in micro CT SkyScan 1173. The produced projection, images, were reconstructed using NRecon (in-house software from SkyScan). The images of urinary stones were analyzed using CT Analyser (CT An) to obtain information of the internal structure and the Hounsfield Unit (HU) value to determine the information regarding the composition of the urinary stones, respectively. The average HU values from certain region of interests in the same slice were compared with spectral curves of known materials from National Institute of Standards and Technology (NIST). From the analysis, the composition of the six scanned stones were obtained. Two stones are composed of cystine, two are composed of struvite, two other stones are composed of struvite+cystine. In conclusion, the single energy micro CT with 80 kV can be used identifying cystine and struvite urinary stone.

Health Utilities of Type 2 Diabetes-Related Complications: A Cross-Sectional Study in Sweden

PubMed Central

Kiadaliri, Aliasghar A.; Gerdtham, Ulf-G; Eliasson, Björn; Gudbjörnsdottir, Soffia; Svensson, Ann-Marie; Steen Carlsson, Katarina

2014-01-01

This study estimates health utilities (HU) in Sweden for a range of type 2 diabetes-related complications using EQ-5D and two alternative tariffs (UK and Swedish) from 1757 patients with type 2 diabetes from the Swedish National Diabetes Register (NDR). Ordinary least squares were used for statistical analysis. Lower HU was found for female gender, younger age at diagnosis, higher BMI, and history of complications. Microvascular and macrovascular complications had the most negative effect on HU among women and men, respectively. The greatest decline in HU was associated with kidney disorders (−0.114) using the UK tariff and stroke (−0.059) using the Swedish tariff. Multiple stroke and non-acute ischaemic heart disease had higher negative effect than a single event. With the UK tariff, each year elapsed since the last microvascular/macrovascular complication was associated with 0.013 and 0.007 units higher HU, respectively. We found important heterogeneities in effects of complications on HU in terms of gender, multiple event, and time. The Swedish tariff gave smaller estimates and so may result in less cost-effective interventions than the UK tariff. These results suggest that incorporating subgroup-specific HU in cost-utility analyses might provide more insight for informed decision-making. PMID:24810579

Making the invisible visible: improving conspicuity of noncalcified gallstones using dual-energy CT.

PubMed

Uyeda, Jennifer W; Richardson, Ian J; Sodickson, Aaron D

2017-12-01

To determine whether virtual monochromatic imaging (VMI) increases detectability of noncalcified gallstones on dual-energy CT (DECT) compared with conventional CT imaging. This retrospective IRB-approved, HIPAA-compliant study included consecutive patients who underwent DECT of the abdomen in the Emergency Department during a 30-month period (July 1, 2013-December 31, 2015), with a comparison US or MR within 1-year. 51 patients (36F, 15M; mean age 52 years) fulfilled the inclusion criteria. All DECT were acquired on a dual-source 128 × 2 slice scanner using either 80/Sn140 or 100/Sn140 kVp pairs. Source images at high and low kVp were used for DE post-processing with VMI. Within 3 mm reconstructed images, regions of interest of 0.5 cm 2 were placed on noncalcified gallstones and bile to record hounsfield units (HU) at VMI energy levels ranging between 40 and 190 keV. Noncalcified gallstones uniformly demonstrated lowest HU at 40 keV and increase at higher keV; the HU of bile varied at higher keV. Few of the noncalcified stones are visible at 70 keV (simulating a conventional 120 kVp scan), with measured contrast (bile-stone HU difference) <10 HU in 78%, 10-20 HU in 20%, and >20 HU in 2%. Contrast was maximal at 40 keV, where 100% demonstrated >20 HU difference from surrounding bile, 75% >44 HU difference, and 50% >60 HU difference. A paired t test demonstrated a significant difference (p < 0.0001) between this stone-bile contrast at 40 vs. 70 keV and 70 vs. 190 keV. Low keV virtual monochromatic imaging increased conspicuity of noncalcified gallstones, improving their detectability.

Additional Value of Transluminal Attenuation Gradient in CT Angiography to Predict Hemodynamic Significance of Coronary Artery Stenosis

PubMed Central

Stuijfzand, Wynand J.; Danad, Ibrahim; Raijmakers, Pieter G.; Marcu, C. Bogdan; Heymans, Martijn W.; van Kuijk, Cornelis C.; van Rossum, Albert C.; Nieman, Koen; Min, James K.; Leipsic, Jonathon; van Royen, Niels; Knaapen, Paul

2015-01-01

OBJECTIVES The current study evaluates the incremental value of transluminal attenuation gradient (TAG), TAG with corrected contrast opacification (CCO), and TAG with exclusion of calcified coronary segments (ExC) over coronary computed tomography angiogram (CTA) alone using fractional flow reserve (FFR) as the gold standard. BACKGROUND TAG is defined as the contrast opacification gradient along the length of a coronary artery on a coronary CTA. Preliminary data suggest that TAG provides additional functional information. Interpretation of TAG is hampered by multiple heartbeat acquisition algorithms and coronary calcifications. Two correction models have been proposed based on either dephasing of contrast delivery by relating coronary density to corresponding descending aortic opacification (TAG-CCO) or excluding calcified coronary segments (TAG-ExC). METHODS Eighty-five patients with intermediate probability of coronary artery disease were prospectively included. All patients underwent step-and-shoot 256-slice coronary CTA. TAG, TAG-CCO, and TAG-ExC analyses were performed followed by invasive coronary angiography in conjunction with FFR measurements of all major coronary branches. RESULTS Thirty-four patients (40%) were diagnosed with hemodynamically-significant coronary artery disease (i.e., FFR ≤0.80). On a per-vessel basis (n = 253), 59 lesions (23%) were graded as hemodynamically significant, and the diagnostic accuracy of coronary CTA (diameter stenosis ≥50%) was 95%, 75%, 98%, and 54% for sensitivity, specificity, negative predictive value, and positive predictive value, respectively. TAG and TAG-ExC did not discriminate between vessels with or without hemodynamically significant lesions (−13.5 ± 17.1 HU [Hounsfield units] × 10 mm−1 vs. −11.6 ± 13.3 HU × 10 mm−1, p = 0.36; and 13.1 ± 15.9 HU × 10 mm−1 vs. −11.4 ± 11.7 HU × 10 mm−1, p = 0.77, respectively). TAG-CCO was lower in vessels with a hemodynamically-significant lesion (−0.050 ± 0.051 10 mm−1 vs. −0.036 ± 0.034 10 mm−1, p = 0.03) and TAG-ExC resulted in a slight improvement of the net reclassification index (0.021, p < 0.05). CONCLUSIONS TAG did not provide incremental diagnostic value over 256-slice coronary CTA alone in assessing the hemodynamic consequences of a coronary stenosis. Correction for temporal nonuniformity of contrast delivery or exclusion of calcified coronary segments slightly enhanced the results. PMID:24631509

The rotating universe.

NASA Astrophysics Data System (ADS)

Surdin, M.

A closed universe obeying the Hubble equation v = Hu·r, where Hu is the Hubble constant, is considered. It is shown that such a universe is equivalent to a universe rotating around one of its diameters at an angular velocity Ωu = Hu. If one revives Blackett's conjecture, viz., a rotating body creates at its center a magnetic dipole, one computes the value of the magnetic field as B ≅ 2.5×10-5G. Intergalactic magnetic fields of the order of 10-6G were deduced from observations.

Prospective evaluation of [11C]Choline PET/CT in therapy response assessment of standardized docetaxel first-line chemotherapy in patients with advanced castration refractory prostate cancer.

PubMed

Schwarzenböck, Sarah M; Eiber, Matthias; Kundt, Günther; Retz, Margitta; Sakretz, Monique; Kurth, Jens; Treiber, Uwe; Nawroth, Roman; Rummeny, Ernst J; Gschwend, Jürgen E; Schwaiger, Markus; Thalgott, Mark; Krause, Bernd J

2016-11-01

The aim of this study was to prospectively evaluate the value of [ 11 C] Choline PET/CT in monitoring early and late response to a standardized first-line docetaxel chemotherapy in castration refractory prostate cancer (mCRPC) patients. Thirty-two patients were referred for [ 11 C] Choline PET/CT before the start of docetaxel chemotherapy, after one and ten chemotherapy cycles (or - in case of discontinuation - after the last administered cycle) for therapy response assessment. [ 11 C] Choline uptake (SUV max , SUV mean ), CT derived Houndsfield units (HU max , HU mean ), and volume of bone, lung, and nodal metastases and local recurrence were measured semi-automatically at these timepoints. Change in SUV max , SUV mean , HU max , HU mean, and volume was assessed between PET 2 and 1 (early response assessment, ERA) and PET 3 and 1 (late response assessment, LRA) on a patient and lesion basis. Results of PET/CT were compared to clinically used RECIST 1.1 and clinical criteria based therapy response assessment including PSA for defining progressive disease (PD) and non-progressive disease (nPD), respectively. Relationships between changes of SUV max and SUV mean (early and late) and changes of PSA early and PSA late were evaluated. Prognostic value of initial SUV max and SUV mean was assessed. Statistical analyses were performed using SPSS. In the patient-based ERA and LRA there were no statistically significant differences in change of choline uptake, HU, and volume between PD and nPD applying RECIST or clinical response criteria. In the lesion-based ERA, decrease in choline uptake of bone metastases was even higher in PD (applying RECIST criteria), whereas in LRA the decrease was higher in nPD (applying clinical criteria). There were only significant correlations between change in choline uptake and PSA in ERA in PD, in LRA no significant correlations were discovered. Initial SUV max and SUV mean were statistically significantly higher in nPD (applying clinical criteria). There is no significant correlation between change in choline uptake in [ 11 C] Choline PET/CT and clinically routinely used objective response assessment during the early and late course of docetaxel chemotherapy. Therefore, [ 11 C] Choline PET/CT seems to be of limited use in therapy response assessment in standardized first-line chemotherapy in mCRPC patients.

SU-F-J-74: High Z Geometric Integrity and Beam Hardening Artifact Assessment Using a Retrospective Metal Artifact Reduction (MAR) Reconstruction Algorithm

DOE Office of Scientific and Technical Information (OSTI.GOV)

Woods, K; DiCostanzo, D; Gupta, N

Purpose: To test the efficacy of a retrospective metal artifact reduction (MAR) reconstruction algorithm for a commercial computed tomography (CT) scanner for radiation therapy purposes. Methods: High Z geometric integrity and artifact reduction analysis was performed with three phantoms using General Electric’s (GE) Discovery CT. The three phantoms included: a Computerized Imaging Reference Systems (CIRS) electron density phantom (Model 062) with a 6.5 mm diameter titanium rod insert, a custom spine phantom using Synthes Spine hardware submerged in water, and a dental phantom with various high Z fillings submerged in water. Each phantom was reconstructed using MAR and compared againstmore » the original scan. Furthermore, each scenario was tested using standard and extended Hounsfield Unit (HU) ranges. High Z geometric integrity was performed using the CIRS phantom, while the artifact reduction was performed using all three phantoms. Results: Geometric integrity of the 6.5 mm diameter rod was slightly overestimated for non-MAR scans for both standard and extended HU. With MAR reconstruction, the rod was underestimated for both standard and extended HU. For artifact reduction, the mean and standard deviation was compared in a volume of interest (VOI) in the surrounding material (water and water equivalent material, ∼0HU). Overall, the mean value of the VOI was closer to 0 HU for the MAR reconstruction compared to the non-MAR scan for most phantoms. Additionally, the standard deviations for all phantoms were greatly reduced using MAR reconstruction. Conclusion: GE’s MAR reconstruction algorithm improves image quality with the presence of high Z material with minimal degradation of its geometric integrity. High Z delineation can be carried out with proper contouring techniques. The effects of beam hardening artifacts are greatly reduced with MAR reconstruction. Tissue corrections due to these artifacts can be eliminated for simple high Z geometries and greatly reduced for more complex geometries.« less

Light curing through glass ceramics: effect of curing mode on micromechanical properties of dual-curing resin cements.

PubMed

Flury, Simon; Lussi, Adrian; Hickel, Reinhard; Ilie, Nicoleta

2014-04-01

The aim of this study was to investigate micromechanical properties of five dual-curing resin cements after different curing modes including light curing through glass ceramic materials. Vickers hardness (VH) and indentation modulus (Y HU) of Panavia F2.0, RelyX Unicem 2 Automix, SpeedCEM, BisCem, and BeautiCem SA were measured after 1 week of storage (37 °C, 100 % humidity). The resin cements were tested following self-curing or light curing with the second-generation light-emitting diode (LED) curing unit Elipar FreeLight 2 in Standard Mode (1,545 mW/cm(2)) or with the third-generation LED curing unit VALO in High Power Mode (1,869 mW/cm(2)) or in XtraPower Mode (3,505 mW/cm(2)). Light curing was performed directly or through glass ceramic discs of 1.5 or 3 mm thickness of IPS Empress CAD or IPS e.max CAD. VH and Y HU were analysed with Kruskal-Wallis tests followed by pairwise Wilcoxon rank sum tests (α = 0.05). RelyX Unicem 2 Automix resulted in the highest VH and Y HU followed by BeautiCem SA, BisCem, SpeedCEM, and finally Panavia F2.0. Self-curing of RelyX Unicem 2 Automix and SpeedCEM lowered VH and Y HU compared to light curing whereas self-curing of Panavia F2.0, BisCem, and BeautiCem SA led to similar or significantly higher VH and Y HU compared to light curing. Generally, direct light curing resulted in similar or lower VH and Y HU compared to light curing through 1.5-mm-thick ceramic discs. Light curing through 3-mm-thick discs of IPS e.max CAD generally reduced VH and Y HU for all resin cements except SpeedCEM, which was the least affected by light curing through ceramic discs. The resin cements responded heterogeneously to changes in curing mode. The applied irradiances and light curing times adequately cured the resin cements even through 1.5-mm-thick ceramic discs. When light curing resin cements through thick glass ceramic restorations, clinicians should consider to prolong the light curing times even with LED curing units providing high irradiances.

Hounsfield units are a useful predictor of pleural effusion cytological type in dogs but not in cats.

PubMed

Woods, Sarah J; Spriet, Mathieu; Safra, Noa; Cissell, Derek D; Borjesson, Dori L

2018-04-23

All categories of pleural effusion subjectively display as soft tissue opacity on computed tomography (CT). Quantitative measurement using Hounsfield units (HU) has the potential to bring additional information regarding the nature of the fluid in a noninvasive way. The purposes of this retrospective cross-sectional analytical study were to compare Hounsfield units of different pleural effusion categories in dogs and cats, assess association between specific cytologic parameters and Hounsfield units, and evaluate the effect of dependent vs. nondependent aspect of the effusion pool on Hounsfield unit. A total of 111 patients (74 dogs and 37 cats) with pleural effusion, that underwent thoracic CT and diagnostic thoracocentesis, were included in the study. Effusions were cytologically categorized as exudate, transudate, modified transudate, hemorrhage, or chyle. Significant differences existed in Hounsfield units between categories in dogs (P < 0.0001) but not in cats (P = 0.334). Canine chylous effusion (6.1 ± 4.7 HU (mean ± standard deviation)) and transudate (5.6 ± 2.0) were significantly lower than exudate (20.3 ± 9.5) and hemorrhage (21.4 ± 9.2). No significant differences were found between modified transudate (13.6 ± 10.3) and other categories. Significant, weak linear correlation was identified in dogs between Hounsfield units and total protein (P = 0.018, R   = 0.089), red blood cells (P = 0.021, R   = 0.077), and total nucleated cells (P = 0.013, R   = 0.089). The Hounsfield units of dependent effusion was not significantly higher than the nondependent effusion, except for canine chylous effusion (P = 0.008). Fourteen Hounsfield units was identified as the most clinically useful threshold: <14 HU identified transudate or chylous effusion with a sensitivity of 100% and a specificity of 69%. A threshold >14 HU had a specificity of 100% and a sensitivity of 69% for identifying exudate, modified transudate, or hemorrhage. © 2018 American College of Veterinary Radiology.

Effect of Hindlimb Unloading on Rat Soleus Fiber Force, Stiffness, and Calcium Sensitivity

NASA Technical Reports Server (NTRS)

McDonald Kerry S.; Fitts, Robert H.

1995-01-01

The purpose of this study was to examine the time course of change in soleus muscle fiber peak force (N), tension (P(sub 0), kN/sq m), elastic modulus (E(sub 0)), and force-pCa and stiffness - pCa relationships. After 1, 2, or 3 wk of Hindlimb Unloading (HU), single fibers were isolated and placed between a motor arm and a transducer, and fiber diameter, peak absolute force, P(sub 0), E(sub 0), and force-pCa and stiffness-pca relationships were characterized. One week of HU resulted in a significant reduction in fiber diameter (68 +/- 2 vs. 57 +/- 1 micrometer), force (3.59 +/- 0.15 vs. 2.19 +/- 0.12 x 10(exp -4) N), P(sub 0) (102 +/- 4 vs. 85 +/- 2 kN/sq m), and E(sub 0) (1.96 +/- 0.12 vs. 1.37 +/- 0.13 X 10(exp 7) N/sq m) and 2 wk of HU caused a further decline in fiber diameter (45 +/- 1 micrometer), force (1.31 +/- 0.06 x 10(exp -4) N), and E(sub 0)(0.96 +/- 0.09 x 10(exp 7) N/sq m). Although the mean fiber diameter and absolute force continued to decline through 3 wk of HU, P(sub 0) recovered to values not significantly different from control. The P(sub 0)/E(sub 0) ratio was significantly increased after 1 (5.5 +/- 0.3 to 7.1 +/- 0.6), 2, and 3 wk of HU, and the 2-wk (9.5 +/- 0.4) and 3-wk (9.4 +/- 0.8) values were significantly greater than the 1-wk values. The force-pCa and stiffness-pCa curves were shifted right- ward after 1, 2, and 3 wk of HU. At 1 wk of HU, the Ca(2+) sensitivity of isometric force, assessed by Ca(2+) concentration required for half-maximal force, was increased from the control value of 1.83 +/- 0.12 to 2.30 +/- 0.10 micrometers. In conclusion, after HU, the decrease in soleus fiber P(sub 0) can be explained by a reduction in the number of myofibrillar cross bridges per cross-sectional area. Our working hypothesis is that the loss of contractile protein reduces the number of cross bridges per cross-sectional area and increases the filament lattice spacing. The increased spacing reduces cross-bridge force and stiffness, but P(sub 0)/E(sub 0) increases because of a quantitatively greater effect on stiffness.

Dose Calculation on KV Cone Beam CT Images: An Investigation of the Hu-Density Conversion Stability and Dose Accuracy Using the Site-Specific Calibration

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rong Yi, E-mail: rong@humonc.wisc.ed; Smilowitz, Jennifer; Tewatia, Dinesh

2010-10-01

Precise calibration of Hounsfield units (HU) to electron density (HU-density) is essential to dose calculation. On-board kV cone beam computed tomography (CBCT) imaging is used predominantly for patients' positioning, but will potentially be used for dose calculation. The impacts of varying 3 imaging parameters (mAs, source-imager distance [SID], and cone angle) and phantom size on the HU number accuracy and HU-density calibrations for CBCT imaging were studied. We proposed a site-specific calibration method to achieve higher accuracy in CBCT image-based dose calculation. Three configurations of the Computerized Imaging Reference Systems (CIRS) water equivalent electron density phantom were used to simulatemore » sites including head, lungs, and lower body (abdomen/pelvis). The planning computed tomography (CT) scan was used as the baseline for comparisons. CBCT scans of these phantom configurations were performed using Varian Trilogy{sup TM} system in a precalibrated mode with fixed tube voltage (125 kVp), but varied mAs, SID, and cone angle. An HU-density curve was generated and evaluated for each set of scan parameters. Three HU-density tables generated using different phantom configurations with the same imaging parameter settings were selected for dose calculation on CBCT images for an accuracy comparison. Changing mAs or SID had small impact on HU numbers. For adipose tissue, the HU discrepancy from the baseline was 20 HU in a small phantom, but 5 times lager in a large phantom. Yet, reducing the cone angle significantly decreases the HU discrepancy. The HU-density table was also affected accordingly. By performing dose comparison between CT and CBCT image-based plans, results showed that using the site-specific HU-density tables to calibrate CBCT images of different sites improves the dose accuracy to {approx}2%. Our phantom study showed that CBCT imaging can be a feasible option for dose computation in adaptive radiotherapy approach if the site-specific calibration is applied.« less

A novel forward projection-based metal artifact reduction method for flat-detector computed tomography.

PubMed

Prell, Daniel; Kyriakou, Yiannis; Beister, Marcel; Kalender, Willi A

2009-11-07

Metallic implants generate streak-like artifacts in flat-detector computed tomography (FD-CT) reconstructed volumetric images. This study presents a novel method for reducing these disturbing artifacts by inserting discarded information into the original rawdata using a three-step correction procedure and working directly with each detector element. Computation times are minimized by completely implementing the correction process on graphics processing units (GPUs). First, the original volume is corrected using a three-dimensional interpolation scheme in the rawdata domain, followed by a second reconstruction. This metal artifact-reduced volume is then segmented into three materials, i.e. air, soft-tissue and bone, using a threshold-based algorithm. Subsequently, a forward projection of the obtained tissue-class model substitutes the missing or corrupted attenuation values directly for each flat detector element that contains attenuation values corresponding to metal parts, followed by a final reconstruction. Experiments using tissue-equivalent phantoms showed a significant reduction of metal artifacts (deviations of CT values after correction compared to measurements without metallic inserts reduced typically to below 20 HU, differences in image noise to below 5 HU) caused by the implants and no significant resolution losses even in areas close to the inserts. To cover a variety of different cases, cadaver measurements and clinical images in the knee, head and spine region were used to investigate the effectiveness and applicability of our method. A comparison to a three-dimensional interpolation correction showed that the new approach outperformed interpolation schemes. Correction times are minimized, and initial and corrected images are made available at almost the same time (12.7 s for the initial reconstruction, 46.2 s for the final corrected image compared to 114.1 s and 355.1 s on central processing units (CPUs)).

Designing, Prototyping and Evaluating Digital Mindfulness Applications: A Case Study of Mindful Breathing for Stress Reduction

PubMed Central

Hedman, Anders; Feng, Shuo; Li, Haibo; Osika, Walter

2017-01-01

Background During the past decade, there has been a rapid increase of interactive apps designed for health and well-being. Yet, little research has been published on developing frameworks for design and evaluation of digital mindfulness facilitating technologies. Moreover, many existing digital mindfulness applications are purely software based. There is room for further exploration and assessment of designs that make more use of physical qualities of artifacts. Objective The study aimed to develop and test a new physical digital mindfulness prototype designed for stress reduction. Methods In this case study, we designed, developed, and evaluated HU, a physical digital mindfulness prototype designed for stress reduction. In the first phase, we used vapor and light to support mindful breathing and invited 25 participants through snowball sampling to test HU. In the second phase, we added sonification. We deployed a package of probes such as photos, diaries, and cards to collect data from users who explored HU in their homes. Thereafter, we evaluated our installation using both self-assessed stress levels and heart rate (HR) and heart rate variability (HRV) measures in a pilot study, in order to measure stress resilience effects. After the experiment, we performed a semistructured interview to reflect on HU and investigate the design of digital mindfulness apps for stress reduction. Results The results of the first phase showed that 22 of 25 participants (88%) claimed vapor and light could be effective ways of promoting mindful breathing. Vapor could potentially support mindful breathing better than light (especially for mindfulness beginners). In addition, a majority of the participants mentioned sound as an alternative medium. In the second phase, we found that participants thought that HU could work well for stress reduction. We compared the effect of silent HU (using light and vapor without sound) and sonified HU on 5 participants. Subjective stress levels were statistically improved with both silent and sonified HU. The mean value of HR using silent HU was significantly lower than resting baseline and sonified HU. The mean value of root mean square of differences (RMSSD) using silent HU was significantly higher than resting baseline. We found that the differences between our objective and subjective assessments were intriguing and prompted us to investigate them further. Conclusions Our evaluation of HU indicated that HU could facilitate relaxed breathing and stress reduction. There was a difference in outcome between the physiological measures of stress and the subjective reports of stress, as well as a large intervariability among study participants. Our conclusion is that the use of stress reduction tools should be customized and that the design work of mindfulness technology for stress reduction is a complex process, which requires cooperation of designers, HCI (Human-Computer Interaction) experts and clinicians. PMID:28615157

SU-C-206-03: Metal Artifact Reduction in X-Ray Computed Tomography Based On Local Anatomical Similarity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dong, X; Yang, X; Rosenfield, J

Purpose: Metal implants such as orthopedic hardware and dental fillings cause severe bright and dark streaking in reconstructed CT images. These artifacts decrease image contrast and degrade HU accuracy, leading to inaccuracies in target delineation and dose calculation. Additionally, such artifacts negatively impact patient set-up in image guided radiation therapy (IGRT). In this work, we propose a novel method for metal artifact reduction which utilizes the anatomical similarity between neighboring CT slices. Methods: Neighboring CT slices show similar anatomy. Based on this anatomical similarity, the proposed method replaces corrupted CT pixels with pixels from adjacent, artifact-free slices. A gamma map,more » which is the weighted summation of relative HU error and distance error, is calculated for each pixel in the artifact-corrupted CT image. The minimum value in each pixel’s gamma map is used to identify a pixel from the adjacent CT slice to replace the corresponding artifact-corrupted pixel. This replacement only occurs if the minimum value in a particular pixel’s gamma map is larger than a threshold. The proposed method was evaluated with clinical images. Results: Highly attenuating dental fillings and hip implants cause severe streaking artifacts on CT images. The proposed method eliminates the dark and bright streaking and improves the implant delineation and visibility. In particular, the image non-uniformity in the central region of interest was reduced from 1.88 and 1.01 to 0.28 and 0.35, respectively. Further, the mean CT HU error was reduced from 328 HU and 460 HU to 60 HU and 36 HU, respectively. Conclusions: The proposed metal artifact reduction method replaces corrupted image pixels with pixels from neighboring slices that are free of metal artifacts. This method proved capable of suppressing streaking artifacts, improving HU accuracy and image detectability.« less

Molecular structure, vibrational spectra and quantum chemical MP2/DFT studies toward the rational design of hydroxyurea imprinted polymer

NASA Astrophysics Data System (ADS)

Prasad, Bhim Bali; Rai, Garima

2013-03-01

In this study, both experimental and theoretical vibrational spectra of template (hydroxyurea, HU), monomer (N-(4,6-bisacryloyl amino-[1,3,5] triazine-2-yl-)-acryl amide, TAT), and HU-TAT complexes were compared and these were respectively found to be in good agreement. Binding energies of HU, when complexed with different monomers, were computed using second order Moller Plesset theory (MP2) at 6-311++G(d,p) level both in the gas as well as solution phases. HU is an antineoplastic agent extensively being used in the treatment of polycythaemia Vera and thrombocythemia. It is also used to reduce the frequency of painful attacks in sickle cell anemia. It has antiretroviral property in disease like AIDS. All spectral characterizations were made using Density Functional Theory (DFT) at B3LYP employing 6-31+g(2d, 2p) basis set. The theoretical values for 13C and 1H NMR chemical shifts were found to be in accordance with the corresponding experimental values. Of all different monomers studied for the synthesis of molecularly imprinted polymer (MIP) systems, the monomer TAT (2 mol) was typically found to have a best binding score requisite for complexation with HU (1 mol) at the ground state.

SU-D-201-02: Prediction of Delivered Dose Based On a Joint Histogram of CT and FDG PET Images

DOE Office of Scientific and Technical Information (OSTI.GOV)

Park, M; Choi, Y; Cho, A

2015-06-15

Purpose: To investigate whether pre-treatment images can be used in predicting microsphere distribution in tumors. When intra-arterial radioembolization using Y90 microspheres was performed, the microspheres were often delivered non-uniformly within the tumor, which could lead to an inefficient therapy. Therefore, it is important to estimate the distribution of microspheres. Methods: Early arterial phase CT and FDG PET images were acquired for patients with primary liver cancer prior to radioembolization (RE) using Y90 microspheres. Tumor volume was delineated on CT images and fused with FDG PET images. From each voxel (3.9×3.9×3.3 mm3) in the tumor, the Hounsfield unit (HU) from themore » CT and SUV values from the FDG PET were harvested. We binned both HU and SUV into 11 bins and then calculated a normalized joint-histogram in an 11×11 array.Patients also underwent a post-treatment Y90 PET imaging. Radiation dose for the tumor was estimated using convolution of the Y90 distribution with a dose-point kernel. We also calculated a fraction of the tumor volume that received a radiation dose great than 100Gy. Results: Averaged over 40 patients, 55% of tumor volume received a dose greater than 100Gy (range : 1.1 – 100%). The width of the joint histogram was narrower for patients with a high dose. For patients with a low dose, the width was wider and a larger fraction of tumor volume had low HU. Conclusion: We have shown the pattern of joint histogram of the HU and SUV depends on delivered dose. The patterns can predict the efficacy of uniform intra-arterial delivery of Y90 microspheres.« less

The value of "liver windows" settings in the detection of small renal cell carcinomas on unenhanced computed tomography.

PubMed

Sahi, Kamal; Jackson, Stuart; Wiebe, Edward; Armstrong, Gavin; Winters, Sean; Moore, Ronald; Low, Gavin

2014-02-01

To assess if "liver window" settings improve the conspicuity of small renal cell carcinomas (RCC). Patients were analysed from our institution's pathology-confirmed RCC database that included the following: (1) stage T1a RCCs, (2) an unenhanced computed tomography (CT) abdomen performed ≤ 6 months before histologic diagnosis, and (3) age ≥ 17 years. Patients with multiple tumours, prior nephrectomy, von Hippel-Lindau disease, and polycystic kidney disease were excluded. The unenhanced CT was analysed, and the tumour locations were confirmed by using corresponding contrast-enhanced CT or magnetic resonance imaging studies. Representative single-slice axial, coronal, and sagittal unenhanced CT images were acquired in "soft tissue windows" (width, 400 Hounsfield unit (HU); level, 40 HU) and liver windows (width, 150 HU; level, 88 HU). In addition, single-slice axial, coronal, and sagittal unenhanced CT images of nontumourous renal tissue (obtained from the same cases) were acquired in soft tissue windows and liver windows. These data sets were randomized, unpaired, and were presented independently to 3 blinded radiologists for analysis. The presence or absence of suspicious findings for tumour was scored on a 5-point confidence scale. Eighty-three of 415 patients met the study criteria. Receiver operating characteristics (ROC) analysis, t test analysis, and kappa analysis were used. ROC analysis showed statistically superior diagnostic performance for liver windows compared with soft tissue windows (area under the curve of 0.923 vs 0.879; P = .0002). Kappa statistics showed "good" vs "moderate" agreement between readers for liver windows compared with soft tissue windows. Use of liver windows settings improves the detection of small RCCs on the unenhanced CT. Copyright © 2014 Canadian Association of Radiologists. Published by Elsevier Inc. All rights reserved.

Use of internal references for assessing CT density measurements of the pelvis as replacement for use of an external phantom.

PubMed

Boomsma, Martijn F; Slouwerhof, Inge; van Dalen, Jorn A; Edens, Mireille A; Mueller, Dirk; Milles, Julien; Maas, Mario

2015-11-01

The purpose of this research is to study the use of an internal reference standard for fat- and muscle as a replacement for an external reference standard with a phantom. By using a phantomless internal reference standard, Hounsfield unit (HU) measurements of various tissues can potentially be assessed in patients with a CT scan of the pelvis without an added phantom at time of CT acquisition. This paves the way for development of a tool for quantification of the change in tissue density in one patient over time and between patients. This could make every CT scan made without contrast available for research purposes. Fifty patients with unilateral metal-on-metal total hip replacements, scanned together with a calibration reference phantom used in bone mineral density measurements, were included in this study. On computed tomography scans of the pelvis without the use of intravenous iodine contrast, reference values for fat and muscle were measured in the phantom as well as within the patient's body. The conformity between the references was examined with the intra-class correlation coefficient. The mean HU (± SD) of reference values for fat for the internal- and phantom references were -91.5 (±7.0) and -90.9 (±7.8), respectively. For muscle, the mean HU (± SD) for the internal- and phantom references were 59.2 (±6.2) and 60.0 (±7.2), respectively. The intra-class correlation coefficients for fat and muscle were 0.90 and 0.84 respectively and show excellent agreement between the phantom and internal references. Internal references can be used with similar accuracy as references from an external phantom. There is no need to use an external phantom to asses CT density measurements of body tissue.

Genes on a Wire: The Nucleoid-Associated Protein HU Insulates Transcription Units in Escherichia coli

PubMed Central

Berger, Michael; Gerganova, Veneta; Berger, Petya; Rapiteanu, Radu; Lisicovas, Viktoras; Dobrindt, Ulrich

2016-01-01

The extent to which chromosomal gene position in prokaryotes affects local gene expression remains an open question. Several studies have shown that chromosomal re-positioning of bacterial transcription units does not alter their expression pattern, except for a general decrease in gene expression levels from chromosomal origin to terminus proximal positions, which is believed to result from gene dosage effects. Surprisingly, the question as to whether this chromosomal context independence is a cis encoded property of a bacterial transcription unit, or if position independence is a property conferred by factors acting in trans, has not been addressed so far. For this purpose, we established a genetic test system assessing the chromosomal positioning effects by means of identical promoter-fluorescent reporter gene fusions inserted equidistantly from OriC into both chromosomal replichores of Escherichia coli K-12. Our investigations of the reporter activities in mutant cells lacking the conserved nucleoid associated protein HU uncovered various drastic chromosomal positional effects on gene transcription. In addition we present evidence that these positional effects are caused by transcriptional activity nearby the insertion site of our reporter modules. We therefore suggest that the nucleoid-associated protein HU is functionally insulating transcription units, most likely by constraining transcription induced DNA supercoiling. PMID:27545593

Feasibility of MR-only proton dose calculations for prostate cancer radiotherapy using a commercial pseudo-CT generation method

NASA Astrophysics Data System (ADS)

Maspero, Matteo; van den Berg, Cornelis A. T.; Landry, Guillaume; Belka, Claus; Parodi, Katia; Seevinck, Peter R.; Raaymakers, Bas W.; Kurz, Christopher

2017-12-01

A magnetic resonance (MR)-only radiotherapy workflow can reduce cost, radiation exposure and uncertainties introduced by CT-MRI registration. A crucial prerequisite is generating the so called pseudo-CT (pCT) images for accurate dose calculation and planning. Many pCT generation methods have been proposed in the scope of photon radiotherapy. This work aims at verifying for the first time whether a commercially available photon-oriented pCT generation method can be employed for accurate intensity-modulated proton therapy (IMPT) dose calculation. A retrospective study was conducted on ten prostate cancer patients. For pCT generation from MR images, a commercial solution for creating bulk-assigned pCTs, called MR for Attenuation Correction (MRCAT), was employed. The assigned pseudo-Hounsfield Unit (HU) values were adapted to yield an increased agreement to the reference CT in terms of proton range. Internal air cavities were copied from the CT to minimise inter-scan differences. CT- and MRCAT-based dose calculations for opposing beam IMPT plans were compared by gamma analysis and evaluation of clinically relevant target and organ at risk dose volume histogram (DVH) parameters. The proton range in beam’s eye view (BEV) was compared using single field uniform dose (SFUD) plans. On average, a (2%, 2 mm) gamma pass rate of 98.4% was obtained using a 10% dose threshold after adaptation of the pseudo-HU values. Mean differences between CT- and MRCAT-based dose in the DVH parameters were below 1 Gy (<1.5% ). The median proton range difference was 0.1 mm, with on average 96% of all BEV dose profiles showing a range agreement better than 3 mm. Results suggest that accurate MR-based proton dose calculation using an automatic commercial bulk-assignment pCT generation method, originally designed for photon radiotherapy, is feasible following adaptation of the assigned pseudo-HU values.

A Numeric Analysis of Bone Density in the Edentulous Interforaminal Region.

PubMed

Tavitian, Patrick; Ruquet, Michel; Mensé, Chloe; Nicolas, Emmanuel; Hue, Olivier

The purpose of this study was to assess the density of interforaminal bone using quantitative computed tomography (QCT) in simulated case histories to be prescribed an All-on-Five fixed implant treatment protocol. QCT scans from 30 edentulous patients (15 men and 15 women; mean age 63.33 ± 9.3 years) were analyzed using the Nobel Clinician software. Densities (in Hounsfield units [HU]) were recorded at the neck, middle part of the body, and apex of the lingual and buccal parts of proposed implant sites. The highest bone densities were measured at the neck of the implant (1,187 ± 382 HU), with lower densities at the apex (774 ± 571 HU) (P < .01). Bone densities decreased on the lingual interforaminal portion of the implant, especially on the two intermediate implants. Bone density was lower in women (917 ± 510 HU) than in men (1,095 ± 601 HU) (P < .01). The interforaminal measured bone densities are lower on the paramedian region of the symphysis and in women. However, these levels are in accordance with immediate loading with a fixed partial denture.

SU-F-J-213: Feasibility Study of Using a Dual-Energy Cone Beam CT (DECBCT) in Proton Therapy Treatment Planning

DOE Office of Scientific and Technical Information (OSTI.GOV)

Peng, H; Xing, L; Kanehira, T

2016-06-15

Purpose: The aim of this study is to evaluate the feasibility of using a dual-energy CBCT (DECBCT) in proton therapy treatment planning to allow for accurate electron density estimation. Methods: For direct comparison, two scenarios were selected: a dual-energy fan-beam CT (high: 140 kVp, low: 80 kVp) and a DECBCT (high: 125 kVp, low: 80 kVp). A Gammex 467 tissue characterization phantom was used, including the rods of air, water, bone (B2–30% mineral), cortical bone (SB3), lung (LN-300), brain, liver and adipose. For the CBCT, Hounsfield Unit (HU) numbers were first obtained from the reconstructed images after a calibration wasmore » made based on water (=0) and air materials (=−1000). For each tissue surrogate, region-of-interest (ROI) analyses were made to derive high-energy and low-energy HU values (HUhigh and HUlow), which were subsequently used to estimate electron density based on the algorithm as previously described by Hunemohr N., et al. Parameters k1 and k2 are energy dependent and can be derived from calibration materials. Results: While for the dual-energy FBCT, the electron density is found be within +/−3% error relative to the values provided by the phantom vendor: −1.8% (water), 0.03% (lung), 1.1% (brain), −2.82% (adipose), −0.49% (liver) and −1.89% (cortical bones). While for the DECBCT, the estimation of electron density exhibits a relatively larger variation: −1.76% (water), −36.7% (lung), −1.92% (brain), −3.43% (adipose), 8.1% (liver) and 9.5% (cortical bones). Conclusion: For DECBCT, the accuracy of electron density estimation is inferior to that of a FBCT, especially for materials of either low-density (lung) or high density (cortical bone) compared to water. Such limitation arises from inaccurate HU number derivation in a CBCT. Advanced scatter-correction and HU calibration routines, as well as the deployment of photon counting CT detectors need be investigated to minimize the difference between FBCT and CBCT.« less

SU-E-T-470: Importance of HU-Mass Density Calibration Technique in Proton Pencil Beam Dose Calculation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Penfold, S; Miller, A

2015-06-15

Purpose: Stoichiometric calibration of Hounsfield Units (HUs) for conversion to proton relative stopping powers (RStPs) is vital for accurate dose calculation in proton therapy. However proton dose distributions are not only dependent on RStP, but also on relative scattering power (RScP) of patient tissues. RScP is approximated from material density but a stoichiometric calibration of HU-density tables is commonly neglected. The purpose of this work was to quantify the difference in calculated dose of a commercial TPS when using HU-density tables based on tissue substitute materials and stoichiometric calibrated ICRU tissues. Methods: Two HU-density calibration tables were generated based onmore » scans of the CIRS electron density phantom. The first table was based directly on measured HU and manufacturer quoted density of tissue substitute materials. The second was based on the same CT scan of the CIRS phantom followed by a stoichiometric calibration of ICRU44 tissue materials. The research version of Pinnacle{sup 3} proton therapy was used to compute dose in a patient CT data set utilizing both HU-density tables. Results: The two HU-density tables showed significant differences for bone tissues; the difference increasing with increasing HU. Differences in density calibration table translated to a difference in calculated RScP of −2.5% for ICRU skeletal muscle and 9.2% for ICRU femur. Dose-volume histogram analysis of a parallel opposed proton therapy prostate plan showed that the difference in calculated dose was negligible when using the two different HU-density calibration tables. Conclusion: The impact of HU-density calibration technique on proton therapy dose calculation was assessed. While differences were found in the calculated RScP of bony tissues, the difference in dose distribution for realistic treatment scenarios was found to be insignificant.« less

An exploratory study on cultural variations in oral health attitudes, behaviour and values of freshman (first-year) dental students.

PubMed

Kawamura, M; Wright, F A C; Declerck, D; Freire, M C M; Hu, D Y; Honkala, E; Lévy, G; Kalwitzki, M; Polychronopoulou, A; Yip, H K; Kinirons, M J; Eli, I; Petti, S; Komabayashi, T; Kim, K J; Razak, A A A; Srisilapanan, P; Kwan, S Y L

2005-08-01

To identify similarities and differences in oral health attitudes, behaviour and values among freshman dental students. Cross-cultural survey of dental students. 18 cultural areas. 904 first-year dental students completed the Hiroshima University-Dental Behavioural Inventory (HU-DBI) translated into their own languages. Individual areas were clustered by similarity in responses to the questions. The first group displayed an 'occidental-culture orientation' with the exception of Brazil (Cluster 1 comprised: Australia, United Kingdom, Ireland, Belgium and Brazil, Cluster 2: Germany, Italy, Finland and France). The second group displayed an 'oriental-cultural orientation' with the exception of Greece and Israel (Cluster 3 comprised: China and Indonesia, and Cluster 4: Japan, Korea, Israel, Hong Kong, Malaysia, Thailand and Greece). Australia and United Kingdom were the countries that were most alike. Ireland was the 'neighbour' to these countries. Greece and Malaysia had similar patterns of oral health behaviour although geographic conditions are very different. Although it was considered that in Hong Kong, occidental nations have affected the development of education, it remained in the oriental-culture group. Comparison with the data from the occidentals indicates that a higher percentage of the orientals put off going to the dentist until they have toothache (p < 0.001). Only a small proportion of the occidentals (8%) reported a perception of inevitability in having false teeth, whereas 33% of the orientals held this fatalistic belief (p = 0.001). Grouping the countries into key cultural orientations and international clusters yielded plausible results, using the HU-DBI.

Accurate tissue characterization in low-dose CT imaging with pure iterative reconstruction.

PubMed

Murphy, Kevin P; McLaughlin, Patrick D; Twomey, Maria; Chan, Vincent E; Moloney, Fiachra; Fung, Adrian J; Chan, Faimee E; Kao, Tafline; O'Neill, Siobhan B; Watson, Benjamin; O'Connor, Owen J; Maher, Michael M

2017-04-01

We assess the ability of low-dose hybrid iterative reconstruction (IR) and 'pure' model-based IR (MBIR) images to maintain accurate Hounsfield unit (HU)-determined tissue characterization. Standard-protocol (SP) and low-dose modified-protocol (MP) CTs were contemporaneously acquired in 34 Crohn's disease patients referred for CT. SP image reconstruction was via the manufacturer's recommendations (60% FBP, filtered back projection; 40% ASiR, Adaptive Statistical iterative Reconstruction; SP-ASiR40). MP data sets underwent four reconstructions (100% FBP; 40% ASiR; 70% ASiR; MBIR). Three observers measured tissue volumes using HU thresholds for fat, soft tissue and bone/contrast on each data set. Analysis was via SPSS. Inter-observer agreement was strong for 1530 datapoints (rs > 0.9). MP-MBIR tissue volume measurement was superior to other MP reconstructions and closely correlated with the reference SP-ASiR40 images for all tissue types. MP-MBIR superiority was most marked for fat volume calculation - close SP-ASiR40 and MP-MBIR Bland-Altman plot correlation was seen with the lowest average difference (336 cm 3 ) when compared with other MP reconstructions. Hounsfield unit-determined tissue volume calculations from MP-MBIR images resulted in values comparable to SP-ASiR40 calculations and values that are superior to MP-ASiR images. Accuracy of estimation of volume of tissues (e.g. fat) using segmentation software on low-dose CT images appears optimal when reconstructed with pure IR. © 2016 The Royal Australian and New Zealand College of Radiologists.

Designing, Prototyping and Evaluating Digital Mindfulness Applications: A Case Study of Mindful Breathing for Stress Reduction.

PubMed

Zhu, Bin; Hedman, Anders; Feng, Shuo; Li, Haibo; Osika, Walter

2017-06-14

During the past decade, there has been a rapid increase of interactive apps designed for health and well-being. Yet, little research has been published on developing frameworks for design and evaluation of digital mindfulness facilitating technologies. Moreover, many existing digital mindfulness applications are purely software based. There is room for further exploration and assessment of designs that make more use of physical qualities of artifacts. The study aimed to develop and test a new physical digital mindfulness prototype designed for stress reduction. In this case study, we designed, developed, and evaluated HU, a physical digital mindfulness prototype designed for stress reduction. In the first phase, we used vapor and light to support mindful breathing and invited 25 participants through snowball sampling to test HU. In the second phase, we added sonification. We deployed a package of probes such as photos, diaries, and cards to collect data from users who explored HU in their homes. Thereafter, we evaluated our installation using both self-assessed stress levels and heart rate (HR) and heart rate variability (HRV) measures in a pilot study, in order to measure stress resilience effects. After the experiment, we performed a semistructured interview to reflect on HU and investigate the design of digital mindfulness apps for stress reduction. The results of the first phase showed that 22 of 25 participants (88%) claimed vapor and light could be effective ways of promoting mindful breathing. Vapor could potentially support mindful breathing better than light (especially for mindfulness beginners). In addition, a majority of the participants mentioned sound as an alternative medium. In the second phase, we found that participants thought that HU could work well for stress reduction. We compared the effect of silent HU (using light and vapor without sound) and sonified HU on 5 participants. Subjective stress levels were statistically improved with both silent and sonified HU. The mean value of HR using silent HU was significantly lower than resting baseline and sonified HU. The mean value of root mean square of differences (RMSSD) using silent HU was significantly higher than resting baseline. We found that the differences between our objective and subjective assessments were intriguing and prompted us to investigate them further. Our evaluation of HU indicated that HU could facilitate relaxed breathing and stress reduction. There was a difference in outcome between the physiological measures of stress and the subjective reports of stress, as well as a large intervariability among study participants. Our conclusion is that the use of stress reduction tools should be customized and that the design work of mindfulness technology for stress reduction is a complex process, which requires cooperation of designers, HCI (Human-Computer Interaction) experts and clinicians. ©Bin Zhu, Anders Hedman, Shuo Feng, Haibo Li, Walter Osika. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 14.06.2017.

Population pharmacokinetics and pharmacodynamics of hydroxyurea in sickle cell anemia patients, a basis for optimizing the dosing regimen

PubMed Central

2011-01-01

Background Hydroxyurea (HU) is the first approved pharmacological treatment of sickle cell anemia (SCA). The objectives of this study were to develop population pharmacokinetic(PK)-pharmacodynamic(PD) models for HU in order to characterize the exposure-efficacy relationships and their variability, compare two dosing regimens by simulations and develop some recommendations for monitoring the treatment. Methods The models were built using population modelling software NONMEM VII based on data from two clinical studies of SCA adult patients receiving 500-2000 mg of HU once daily. Fetal hemoglobin percentage (HbF%) and mean corpuscular volume (MCV) were used as biomarkers for response. A sequential modelling approach was applied. Models were evaluated using simulation-based techniques. Comparisons of two dosing regimens were performed by simulating 10000 patients in each arm during 12 months. Results The PK profiles were described by a bicompartmental model. The median (and interindividual coefficient of variation (CV)) of clearance was 11.6 L/h (30%), the central volume was 45.3 L (35%). PK steady-state was reached in about 35 days. For a given dosing regimen, HU exposure varied approximately fivefold among patients. The dynamics of HbF% and MCV were described by turnover models with inhibition of elimination of response. In the studied range of drug exposures, the effect of HU on HbF% was at its maximum (median Imax was 0.57, CV was 27%); the effect on MCV was close to its maximum, with median value of 0.14 and CV of 49%. Simulations showed that 95% of the steady-state levels of HbF% and MCV need 26 months and 3 months to be reached, respectively. The CV of the steady-state value of HbF% was about 7 times larger than that of MCV. Simulations with two different dosing regimens showed that continuous dosing led to a stronger HbF% increase in some patients. Conclusions The high variability of response to HU was related in part to pharmacokinetics and to pharmacodynamics. The steady-state value of MCV at month 3 is not predictive of the HbF% value at month 26. Hence, HbF% level may be a better biomarker for monitoring HU treatment. Continuous dosing might be more advantageous in terms of HbF% for patients who have a strong response to HU. Trial Registration The clinical studies whose data are analysed and reported in this work were not required to be registered in France at their time. Both studies were approved by local ethics committees (of Mondor Hospital and of Kremlin-Bicetre Hospital) and written informed consent was obtained from each patient. PMID:21619673

Anti-Inflammatory and Osteoprotective Effects of Cannabinoid-2 Receptor Agonist HU-308 in a Rat Model of Lipopolysaccharide-Induced Periodontitis.

PubMed

Ossola, Cesar A; Surkin, Pablo N; Mohn, Claudia E; Elverdin, Juan C; Fernández-Solari, Javier

2016-06-01

Anti-inflammatory and immunologic properties of cannabinoids have been reported in several tissues. Expression of cannabinoid receptor Type 2 was reported in osteoblasts and osteoclasts, suggesting a key role in bone metabolism. The aim of this study is to assess the effect of treatment with cannabinoid-2 receptor agonist HU-308 in the oral health of rats subjected to lipopolysaccharide (LPS)-induced periodontitis. Twenty-four rats were distributed in four groups (six rats per group): 1) control rats; 2) sham rats; 3) rats submitted to experimental periodontitis (LPS); and 4) rats submitted to experimental periodontitis and treated with HU-308 (LPS+HU). In groups LPS and LPS+HU, periodontitis was induced by LPS (1 mg/mL) injected into the gingival tissue (GT) of maxillary and mandibular first molars and into the interdental space between the first and second molars, 3 days per week for 6 weeks. In group LPS+HU, HU-308 (500 ng/mL) was applied topically to the GT daily. Alveolar bone loss resulting from LPS-induced periodontitis was significantly attenuated with HU-308 treatment (LPS+HU), measured by macroscopic and histologic examination. Treatment also reduced gingival production of inflammatory mediators augmented in LPS-injected rats, such as: 1) inducible nitric oxide (iNOS) activity (LPS: 90.18 ± 36.51 pmol/minute/mg protein versus LPS+HU: 16.37 ± 4.73 pmol/minute/mg protein; P <0.05); 2) tumor necrosis factor alpha (LPS: 185.70 ± 25.63 pg/mg protein versus LPS+HU: 95.89 ± 17.47 pg/mg protein; P <0.05); and 3) prostaglandin E2 (PGE2) (LPS: 159.20 ± 38.70 pg/mg wet weight versus LPS+HU: 71.25 ± 17.75 pg/mg wet weight; P <0.05). Additionally, HU-308 treatment prevented the inhibitory effect of LPS-induced periodontitis on the salivary secretory response to pilocarpine. Moreover, iNOS activity and PGE2 content, which were increased by LPS-induced periodontitis in the submandibular gland, returned to control values after HU-308 treatment. This study demonstrates anti-inflammatory, osteoprotective, and prohomeostatic effects of HU-308 in oral tissues of rats with LPS-induced periodontitis.

Recombinant human erythropoietin in the prevention of late anemia in intrauterine transfused neonates with Rh-isoimmunization.

PubMed

Zuppa, Antonio Alberto; Alighieri, Giovanni; Calabrese, Valentina; Visintini, Federica; Cota, Francesco; Carducci, Chiara; Antichi, Eleonora; Noia, Giuseppe Antonio; Fortunato, Giuseppe; Romagnoli, Costantino

2010-04-01

The majority of neonates with Rh-isoimmunization develops late anemia between the second and the sixth week of life. We report the effectiveness of recombinant human erythropoietin (rHuEPO) in preventing late anemia in 25 intrauterine and nonintrauterine-transfused neonates. The neonates were treated from 11+/-4 days after birth to 26+/-14 days (400 U/kg/d of rHuEpo, administered subcutaneously). During rHuEpo therapy, vitamin E, calcium folinate, and iron maltose were administered intramuscularly on a daily basis. Hematocrit, platelet, and neutrophil counts did not differ significantly before and after 21-days therapy. However, average values for reticulocyte showed a significant increase. The hematocrit values in the non-intrauterine transfusion (IUT) group increased progressively from the beginning to the end of the treatment, whereas that in the IUT group remained stable. Reticulocyte count increased during treatment in both groups, but it was significantly elevated in the non-IUT group only. Moreover, we observed that only neonates transfused with IUTs needed transfusions before and after treatment. This study suggests the effectiveness of rHuEpo therapy in the treatment of neonates with Rh-isoimmunization and it highlights how IUTs decrease the neonatal response efficacy. Larger, better if multicentric, randomized controlled trial are needed to definitely state whether rHuEPO safely decreases the incidence of late onset anemia.

Genetic diversity and population structure in the narrow endemic Chinese walnut Juglans hopeiensis Hu: implications for conservation

Treesearch

Yiheng Hu; Meng Dang; Xiaojia Feng; Keith Woeste; Peng Zhao

2017-01-01

The conservation of narrow endemic species relies on accurate information regarding their population structure. Juglans hopeiensis Hu (Ma walnut), found only in Hebei province, Beijing, and Tianjin, China, is a threatened tree species valued commercially for its nut and wood. Sequences of two maternally inherited mitochondrial markers and two...

Kilovoltage cone-beam CT: Comparative dose and image quality evaluations in partial and full-angle scan protocols

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kim, Sangroh; Yoo, Sua; Yin Fangfang

2010-07-15

Purpose: To assess imaging dose of partial and full-angle kilovoltage CBCT scan protocols and to evaluate image quality for each protocol. Methods: The authors obtained the CT dose index (CTDI) of the kilovoltage CBCT protocols in an on-board imager by ion chamber (IC) measurements and Monte Carlo (MC) simulations. A total of six new CBCT scan protocols were evaluated: Standard-dose head (100 kVp, 151 mA s, partial-angle), low-dose head (100 kVp, 75 mA s, partial-angle), high-quality head (100 kVp, 754 mA s, partial-angle), pelvis (125 kVp, 706 mA s, full-angle), pelvis spotlight (125 kVp, 752 mA s, partial-angle), and low-dosemore » thorax (110 kVp, 271 mA s, full-angle). Using the point dose method, various CTDI values were calculated by (1) the conventional weighted CTDI (CTDI{sub w}) calculation and (2) Bakalyar's method (CTDI{sub wb}). The MC simulations were performed to obtain the CTDI{sub w} and CTDI{sub wb}, as well as from (3) central slice averaging (CTDI{sub 2D}) and (4) volume averaging (CTDI{sub 3D}) techniques. The CTDI values of the new protocols were compared to those of the old protocols (full-angle CBCT protocols). Image quality of the new protocols was evaluated following the CBCT image quality assurance (QA) protocol [S. Yoo et al., ''A quality assurance program for the on-board imager registered ,'' Med. Phys. 33(11), 4431-4447 (2006)] testing Hounsfield unit (HU) linearity, spatial linearity/resolution, contrast resolution, and HU uniformity. Results: The CTDI{sub w} were found as 6.0, 3.2, 29.0, 25.4, 23.8, and 7.7 mGy for the new protocols, respectively. The CTDI{sub w} and CTDI{sub wb} differed within +3% between IC measurements and MC simulations. Method (2) results were within {+-}12% of method (1). In MC simulations, the CTDI{sub w} and CTDI{sub wb} were comparable to the CTDI{sub 2D} and CTDI{sub 3D} with the differences ranging from -4.3% to 20.6%. The CTDI{sub 3D} were smallest among all the CTDI values. CTDI{sub w} of the new protocols were found as {approx}14 times lower for standard head scan and 1.8 times lower for standard body scan than the old protocols, respectively. In the image quality QA tests, all the protocols except low-dose head and low-dose thorax protocols were within the tolerance in the HU verification test. The HU value for the two protocols was always higher than the nominal value. All the protocols passed the spatial linearity/resolution and HU uniformity tests. In the contrast resolution test, only high-quality head and pelvis scan protocols were within the tolerance. In addition, crescent effect was found in the partial-angle scan protocols. Conclusions: The authors found that CTDI{sub w} of the new CBCT protocols has been significantly reduced compared to the old protocols with acceptable image quality. The CTDI{sub w} values in the point dose method were close to the volume averaging method within 9%-21% for all the CBCT scan protocols. The Bakalyar's method produced more accurate dose estimation within 14%. The HU inaccuracy from low-dose head and low-dose thorax protocols can render incorrect dose results in the treatment planning system. When high soft-tissue contrast data are desired, high-quality head or pelvis scan protocol is recommended depending on the imaging area. The point dose method can be applicable to estimate CBCT dose with reasonable accuracy in the clinical environment.« less

Nanoengineered multimodal contrast agent for medical image guidance

NASA Astrophysics Data System (ADS)

Perkins, Gregory J.; Zheng, Jinzi; Brock, Kristy; Allen, Christine; Jaffray, David A.

2005-04-01

Multimodality imaging has gained momentum in radiation therapy planning and image-guided treatment delivery. Specifically, computed tomography (CT) and magnetic resonance (MR) imaging are two complementary imaging modalities often utilized in radiation therapy for visualization of anatomical structures for tumour delineation and accurate registration of image data sets for volumetric dose calculation. The development of a multimodal contrast agent for CT and MR with prolonged in vivo residence time would provide long-lasting spatial and temporal correspondence of the anatomical features of interest, and therefore facilitate multimodal image registration, treatment planning and delivery. The multimodal contrast agent investigated consists of nano-sized stealth liposomes encapsulating conventional iodine and gadolinium-based contrast agents. The average loading achieved was 33.5 +/- 7.1 mg/mL of iodine for iohexol and 9.8 +/- 2.0 mg/mL of gadolinium for gadoteridol. The average liposome diameter was 46.2 +/- 13.5 nm. The system was found to be stable in physiological buffer over a 15-day period, releasing 11.9 +/- 1.1% and 11.2 +/- 0.9% of the total amounts of iohexol and gadoteridol loaded, respectively. 200 minutes following in vivo administration, the contrast agent maintained a relative contrast enhancement of 81.4 +/- 13.05 differential Hounsfield units (ΔHU) in CT (40% decrease from the peak signal value achieved 3 minutes post-injection) and 731.9 +/- 144.2 differential signal intensity (ΔSI) in MR (46% decrease from the peak signal value achieved 3 minutes post-injection) in the blood (aorta), a relative contrast enhancement of 38.0 +/- 5.1 ΔHU (42% decrease from the peak signal value achieved 3 minutes post-injection) and 178.6 +/- 41.4 ΔSI (62% decrease from the peak signal value achieved 3 minutes post-injection) in the liver (parenchyma), a relative contrast enhancement of 9.1 +/- 1.7 ΔHU (94% decrease from the peak signal value achieved 3 minutes post-injection) and 461.7 +/- 78.1 ΔSI (60% decrease from the peak signal value achieved 5 minutes post-injection) in the kidney (cortex) of a New Zealand white rabbit. This multimodal contrast agent, with prolonged in vivo residence time and imaging efficacy, has the potential to bring about improvements in the fields of medical imaging and radiation therapy, particularly for image registration and guidance.

Feasibility of using 'lung density' values estimated from EIT images for clinical diagnosis of lung abnormalities in mechanically ventilated ICU patients.

PubMed

Nebuya, Satoru; Koike, Tomotaka; Imai, Hiroshi; Iwashita, Yoshiaki; Brown, Brian H; Soma, Kazui

2015-06-01

This paper reports on the results of a study which compares lung density values obtained from electrical impedance tomography (EIT), clinical diagnosis and CT values (HU) within a region of interest in the lung. The purpose was to assess the clinical use of lung density estimation using EIT data. In 11 patients supported by a mechanical ventilator, the consistency of regional lung density measurements as estimated by EIT was validated to assess the feasibility of its use in intensive care medicine. There were significant differences in regional lung densities recorded in the supine position between normal lungs and diseased lungs associated with pneumonia, atelectasis and pleural effusion (normal; 240 ± 71.7 kg m(-3), pneumonia; 306 ± 38.6 kg m(-3), atelectasis; 497 ± 130 kg m(-3), pleural effusion; 467 ± 113 kg m(-3): Steel-Dwass test, p < 0.05). In addition, in order to compare lung density with CT image pixels, the image resolution of CT images, which was originally 512 × 512 pixels, was changed to 16 × 16 pixels to match that of the EIT images. The results of CT and EIT images from five patients in an intensive care unit showed a correlation coefficient of 0.66 ± 0.13 between the CT values (HU) and the lung density values (kg m(-3)) obtained from EIT. These results indicate that it may be possible to obtain a quantitative value for regional lung density using EIT.

SU-E-J-122: The CBCT Dose Calculation Using a Patient Specific CBCT Number to Mass Density Conversion Curve Based On a Novel Image Registration and Organ Mapping Method in Head-And-Neck Radiation Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhou, J; Lasio, G; Chen, S

2015-06-15

Purpose: To develop a CBCT HU correction method using a patient specific HU to mass density conversion curve based on a novel image registration and organ mapping method for head-and-neck radiation therapy. Methods: There are three steps to generate a patient specific CBCT HU to mass density conversion curve. First, we developed a novel robust image registration method based on sparseness analysis to register the planning CT (PCT) and the CBCT. Second, a novel organ mapping method was developed to transfer the organs at risk (OAR) contours from the PCT to the CBCT and corresponding mean HU values of eachmore » OAR were measured in both the PCT and CBCT volumes. Third, a set of PCT and CBCT HU to mass density conversion curves were created based on the mean HU values of OARs and the corresponding mass density of the OAR in the PCT. Then, we compared our proposed conversion curve with the traditional Catphan phantom based CBCT HU to mass density calibration curve. Both curves were input into the treatment planning system (TPS) for dose calculation. Last, the PTV and OAR doses, DVH and dose distributions of CBCT plans are compared to the original treatment plan. Results: One head-and-neck cases which contained a pair of PCT and CBCT was used. The dose differences between the PCT and CBCT plans using the proposed method are −1.33% for the mean PTV, 0.06% for PTV D95%, and −0.56% for the left neck. The dose differences between plans of PCT and CBCT corrected using the CATPhan based method are −4.39% for mean PTV, 4.07% for PTV D95%, and −2.01% for the left neck. Conclusion: The proposed CBCT HU correction method achieves better agreement with the original treatment plan compared to the traditional CATPhan based calibration method.« less

Association of Condylar Bone Quality with TMJ Osteoarthritis.

PubMed

Shi, J; Lee, S; Pan, H C; Mohammad, A; Lin, A; Guo, W; Chen, E; Ahn, A; Li, J; Ting, K; Kwak, J H

2017-07-01

The etiology and treatment of temporomandibular joint (TMJ) osteoarthritis (TMJOA) remain complex and unclear. Based on clinical observations, we hypothesized that low condylar bone quality is significantly correlated with TMJOA and explored this association in a cross-sectional study with human patients. A total of 254 postmenopausal female participants were included in this study. Radiographic findings from cone beam computed tomography (CBCT) and clinical symptoms were used to classify each TMJ data sample as healthy control ( n = 124) or TMJOA ( n = 130). Condylar bone mineral density (BMD) (computed tomography Hounsfield unit [CT HU]) and bone volume fraction (BV/TV) were measured and modeled as predictors of healthy control versus TMJOA status in multilevel logistic regression analyses. Both CT HU (adjusted odds ratio [AOR] = 0.9989, interquartile odds ratio [IOR] = 0.4206) and BV/TV (AOR= 0.8096, IOR = 0.1769) were negatively associated with TMJOA ( P = 0.049, 0.011, respectively). To assess the diagnostic performance of CT HU and BV/TV for identification of TMJOA, receiver operating characteristic (ROC) curves were plotted. The estimated areas under the curve (AUC) were 0.6622 for BV/TV alone, 0.6074 for CT HU alone, and 0.7136 for CT HU and BV/TV together. The model incorporating CT HU and BV/TV together had a significantly higher AUC than the models using BV/TV alone ( P = 0.038) or HU alone ( P = 0.021). In conclusion, we found that low condylar bone quality was significantly correlated with TMJOA development and that condylar CT HU and BV/TV can be used together as a potential diagnostic tool for TMJOA. Careful clinical evaluation of the condyle coupled with appropriate radiographic interpretation would thus be critical for the early detection of TMJOA.

Clarifying the Links Among Online Gaming, Internet Use, Drinking Motives, and Online Pornography Use.

PubMed

Bőthe, Beáta; Tóth-Király, István; Orosz, Gábor

2015-04-01

This study was aimed at investigating the links between online gaming and online pornography use by considering gender, problematic Internet use, and different motives for alcohol drinking. University students (n=512; mean age=22.11 years; standard deviation=2.43 years; 64.06 percent women) filled in the Cyber Pornography Use Inventory, Hungarian version, the Problematic Online Gaming Questionnaire, Hungarian version (POGQ-HU), the Problematic Internet Use Questionnaire, Hungarian version (PIUQ-HU), and the Drinking Motive Questionnaire Revised Short Form, Hungarian version (DMQ-R-HU SF) questionnaires. According to hierarchical multiple regression analyses, the neglect factor of PIUQ-HU, the conformity factor of DMQ-R-HU SF, and the immersion and preoccupation factors of POGQ-HU have a significant predictive value on one's online pornography use, but gender does not. This research shows that independently from the effect of Internet and alcohol use dimensions, immersion and preoccupation factors of online gaming have significant effects on online pornography use. However, preoccupation has a negative effect on pornography use. Players scoring high on this subscale may think about gaming as the only interesting activity that rates higher than even pornography.

Virtual non-contrast in second-generation, dual-energy computed tomography: reliability of attenuation values.

PubMed

Toepker, Michael; Moritz, Thomas; Krauss, Bernhard; Weber, Michael; Euller, Gordon; Mang, Thomas; Wolf, Florian; Herold, Christian J; Ringl, Helmut

2012-03-01

To evaluate the reliability of attenuation values in virtual non-contrast images (VNC) reconstructed from contrast-enhanced, dual-energy scans performed on a second-generation dual-energy CT scanner, compared to single-energy, non-contrast images (TNC). Sixteen phantoms containing a mixture of contrast agent and water at different attenuations (0-1400 HU) were investigated on a Definition Flash-CT scanner using a single-energy scan at 120 kV and a DE-CT protocol (100 kV/SN140 kV). For clinical assessment, 86 patients who received a dual-phase CT, containing an unenhanced single-energy scan at 120 kV and a contrast enhanced (110 ml Iomeron 400 mg/ml; 4 ml/s) DE-CT (100 kV/SN140 kV) in an arterial (n=43) or a venous phase, were retrospectively analyzed. Mean attenuation was measured within regions of interest of the phantoms and in different tissue types of the patients within the corresponding VNC and TNC images. Paired t-tests and Pearson correlation were used for statistical analysis. For all phantoms, mean attenuation in VNC was 5.3±18.4 HU, with respect to water. In 86 patients overall, 2637 regions were measured in TNC and VNC images, with a mean difference between TNC and VNC of -3.6±8.3 HU. In 91.5% (n=2412) of all cases, absolute differences between TNC and VNC were under 15HU, and, in 75.3% (n=1986), differences were under 10 HU. Second-generation dual-energy CT based VNC images provide attenuation values close to those of TNC. To avoid possible outliers multiple measurements are recommended especially for measurements in the spleen, the mesenteric fat, and the aorta. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Association of Hematological Nadirs and Survival in a Nonhuman Primate Model of Hematopoietic Syndrome of Acute Radiation Syndrome.

PubMed

Gluzman-Poltorak, Zoya; Vainstein, Vladimir; Basile, Lena A

2015-08-01

Recombinant human interleukin-12 (rHuIL-12) mitigates the hematopoietic subsyndrome of acute radiation syndrome (HSARS) after total body irradiation (TBI) in a nonhuman primate (NHP) model of HSARS. The mechanism for this effect appears to involve multiple effects of rHuIL-12 on hematopoiesis. We conducted a meta-analysis to examine hematological nadirs and survival across our three NHP completed studies. Animals were irradiated (700 cGy) and treated with a single subcutaneous injection of vehicle (n = 64) or rHuIL-12 (50-500 ng/kg; n = 108) 24-25 h after irradiation, or with daily subcutaneous injections of granulocyte-colony stimulating factor (G-CSF; 10 μg/kg/day) for 18 days starting 24-25 h after exposure (n = 26). Blood samples were obtained at various time points up to day 60 after TBI. Lymphocytes, neutrophils and platelets were significantly lower in nonsurvivors than in survivors in the overall sample and in each treatment group (P < 0.001 for each comparison, Wilcoxon rank-sum test). Lymphocyte nadir was the strongest and most consistent predictor of death by Spearman's rank correlation. Receiver operating characteristic (ROC) curve analysis of death and threshold hematologic nadir values (where nadir values less than or equal the threshold are predictive of death) showed that a threshold of 0.08 × 10(9)/L for lymphocytes had the largest positive predictive value of death (97.2% and 92.5% for the control and rHuIL-12 groups, respectively) and high sensitivity (76.1% and 62.7%, respectively), consistent with human radiation victims data. The current findings suggest that enhanced early bone marrow regeneration resulting in increases in nadir values for all major blood cell types may be the main mechanism of action by which rHuIL-12 mitigates the lethality of HSARS.

NOTE: Ranges of ions in metals for use in particle treatment planning

NASA Astrophysics Data System (ADS)

Jäkel, Oliver

2006-05-01

In proton and ion radiotherapy, the range of particles is calculated from x-ray computed tomography (CT) numbers. Due to the strong absorption of x-rays in a metal and a cut-off for large Hounsfield units (HU) in the software of most CT-scanners, a range calculation in metals cannot be based on the measured HU. This is of special importance when metal implants such as gold fillings or hip prostheses are close to the treatment volume. In order to overcome this problem in treatment planning for heavy charged particles, the correct ranges of ions in the metal relative to water have to be assigned in the CT data. Measurements and calculations of carbon ion ranges in various metals are presented that can be used in treatment planning to allow for a more accurate range calculation of carbon ion beams in titanium, steel, tungsten and gold. The suggested values for the relative water-equivalent range and their uncertainties are 3.13 (±3%) for titanium, 5.59 (±3%) for stainless steel and 10.25 (±4%) for gold.

Matching the oculomotor drive during head-restrained and head-unrestrained gaze shifts in monkey.

PubMed

Bechara, Bernard P; Gandhi, Neeraj J

2010-08-01

High-frequency burst neurons in the pons provide the eye velocity command (equivalently, the primary oculomotor drive) to the abducens nucleus for generation of the horizontal component of both head-restrained (HR) and head-unrestrained (HU) gaze shifts. We sought to characterize how gaze and its eye-in-head component differ when an "identical" oculomotor drive is used to produce HR and HU movements. To address this objective, the activities of pontine burst neurons were recorded during horizontal HR and HU gaze shifts. The burst profile recorded on each HU trial was compared with the burst waveform of every HR trial obtained for the same neuron. The oculomotor drive was assumed to be comparable for the pair yielding the lowest root-mean-squared error. For matched pairs of HR and HU trials, the peak eye-in-head velocity was substantially smaller in the HU condition, and the reduction was usually greater than the peak head velocity of the HU trial. A time-varying attenuation index, defined as the difference in HR and HU eye velocity waveforms divided by head velocity [alpha = (H(hr) - E(hu))/H] was computed. The index was variable at the onset of the gaze shift, but it settled at values several times greater than 1. The index then decreased gradually during the movement and stabilized at 1 around the end of gaze shift. These results imply that substantial attenuation in eye velocity occurs, at least partially, downstream of the burst neurons. We speculate on the potential roles of burst-tonic neurons in the neural integrator and various cell types in the vestibular nuclei in mediating the attenuation in eye velocity in the presence of head movements.

Purification of human erythropoietin by affinity chromatography using cyclic peptide ligands.

PubMed

Kish, William S; Roach, Matthew K; Sachi, Hiroyuki; Naik, Amith D; Menegatti, Stefano; Carbonell, Ruben G

2018-05-15

Prior work described the identification and characterization of erythropoietin-binding cyclic peptides SLFFLH, VVFFVH, FSLLHH and FSLLSH (all of the form cyclo[(N α -Ac)Dap(A)-X 1 -X 6 -AE], wherein X 1 -X 6 is the listed sequences). In this work, the peptide ligands were synthesized on Toyopearl chromatographic resins and utilized for purifying recombinant human erythropoietin (rHuEPO) from complex sources. Elution buffer pH and composition were optimized to maximize the recovery of standard rHuEPO from the peptide resins. The peptide-based adsorbents were employed for separating rHuEPO from a mixture of albumin, myoglobin, and IgG to examine their selectivity. When using FSLLHH, the inclusion of low amounts of surfactants in the wash and elution buffers facilitated the recovery of rHuEPO with high yield and purity. Specifically, FSLLSH and VVFFVH afforded the most efficient separation of rHuEPO, with yield and purity of 85% and 95-97%, respectively. The affinity resins were also utilized to purify rHuEPO from spiked CHO cell culture fluid. In particular, FSLLSH provided the most successful separation from CHO, with yield and purity above 90%, and 1.0 log 10 reduction of host cell proteins. The influence of conductivity and pH in the CHO-rHuEPO load was investigated. Finally, FSLLSH-based resins were used to purify rHuEPO spiked into a Pichia pastoris cell culture fluid, resulting in product yield and purity of 96% and 84%, respectively, and 1.3 log 10 reduction of host DNA. These results compare well with values obtained using wheat germ agglutinin agarose and clearly indicate the potential of the cyclic peptide resins as a viable tool for rHuEPO purification. Copyright © 2018 Elsevier B.V. All rights reserved.

Alpha-thalassaemia and response to hydroxyurea in sickle cell anaemia.

PubMed

Darbari, Deepika S; Nouraie, Mehdi; Taylor, James G; Brugnara, Carlo; Castro, Oswaldo; Ballas, Samir K

2014-04-01

Hydroxyurea (HU) reduces vaso-occlusive crises (VOC) and other complications of sickle cell anaemia (SCA). Alpha-thalassaemia is a known modifier of SCA. Studies on the efficacy of HU in SCA patients with α-thalassaemia have yielded varying results. To determine the effect of α-thalassaemia in response to HU therapy in the Multicenter Study of Hydroxyurea (MSH) cohort. We compared the laboratory parameters and VOC incidence in the MSH cohort stratified by the presence or the absence of α-thalassaemia. Hydroxyurea showed significant (P = 0.001 for all baseline vs. follow-up comparisons) treatment effect on red cell indices irrespective of α-globin gene deletion. The magnitude of the HU-related changes was similar for mean corpuscular volume (MCV) (no α-thalassaemia 13 fl and α-thalassaemia 13 fl) and mean corpuscular haemoglobin (MCH) (no α-thalassaemia 4 pg and α-thalassaemia 4 pg) in both groups. Foetal haemoglobin (HbF) and F-cells also increased significantly with HU treatment in both groups. Total haemoglobin increased after HU treatment in both groups, but the increase was smaller and not statistically significant in patients with α-thalassaemia. In contrast, HU-related reduction in VOCs was more pronounced in patients with α-thalassaemia (VOC incidence rate ratio HU/placebo: 0.63 for α-thalassaemia and 0.54 for no α-thalassaemia (P for interaction 0.003). Hydroxyurea decreases VOCs in SCA patients with and without α-thalassaemia, and the degree of VOC reduction was more pronounced in the patients with alpha-thalassaemia. Despite the lower baseline values, changes in standard laboratory parameters such as MCV and HbF percent remain useful in monitoring HU therapy in the presence of α-thalassaemia. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Effects of hydroxyurea on blood rheology in sickle cell anemia: A two-years follow-up study.

PubMed

Lemonne, Nathalie; Möckesch, Berenike; Charlot, Keyne; Garnier, Yohann; Waltz, Xavier; Lamarre, Yann; Antoine-Jonville, Sophie; Etienne-Julan, Maryse; Hardy-Dessources, Marie-Dominique; Romana, Marc; Connes, Philippe

2017-01-01

The aim of the present study was to test the effects of hydroxyurea (HU) therapy on clinical, hematological and hemorheological parameters in adult patients with sickle cell anemia (SCA). Hematological and hemorheological parameters were measured in 28 SCA patients before HU therapy (i.e., baseline) and at 6, 12 and 24 months of treatment. RBC deformability was determined by ektacytometry at 30 Pa. RBC aggregation properties were investigated by light-backscatter method. Blood viscosity was measured at 225 s-1 by a cone-plate viscometer. The rates of vaso-occlusive crises and acute chest syndrome were lower at 1 and 2 years of HU therapy compared to baseline. The proportion of patients with leg ulcers tended to decrease after 2 years of treatment. Hemoglobin oxygen saturation improved with HU therapy. HU therapy induced a decrease of platelet and white blood cell counts and a rise in fetal hemoglobin level and mean cell volume. While hemoglobin concentrations increased under HU, blood viscosity remained unchanged all along the study. RBC deformability increased over baseline values at 6 months of HU therapy and continued to rise until the end of the follow-up period. In conclusion, the improvement in RBC deformability probably compensates the increase of hemoglobin on blood viscosity and participates to the improvement of the clinical status of patients.

BDNF contributes to IBS-like colonic hypersensitivity via activating the enteroglia-nerve unit

PubMed Central

Wang, Peng; Du, Chao; Chen, Fei-Xue; Li, Chang-Qing; Yu, Yan-Bo; Han, Ting; Akhtar, Suhail; Zuo, Xiu-Li; Tan, Xiao-Di; Li, Yan-Qing

2016-01-01

The over-expressed colonic brain-derived neurotrophic factor (BDNF) has been reported to be associated with abdominal pain in patients with irritable bowel syndrome (IBS). However, the neuropathological mechanism is unclear. We here investigated the involvement of enteroglial cells (EGCs) and enteric nerves in IBS-like visceral hypersensitivity. We showed that glial fibrillary acidic protein (GFAP), tyrosine receptor kinase B (TrkB) and substance P (SP) were significantly increased in the colonic mucosa of IBS patients. The upregulation of those proteins was also observed in the colon of mice with visceral hypersensitivity, but not in the colon of BDNF+/− mice. Functionally, TrkB or EGC inhibitors, or BDNF knockdown significantly suppressed visceral hypersensitivity in mice. Using the EGC cell line, we found that recombinant human BDNF (r-HuBDNF) could directly activate EGCs via the TrkB-phospholipase Cγ1 pathway, thereby inducing a significant upregulation of SP. Moreover, supernatants from r-HuBDNF-activated EGC culture medium, rather than r-HuBDNF alone, triggered markedly augmented discharges in isolated intestinal mesenteric afferent nerves. r-HuBDNF alone could cause mesenteric afferent mechanical hypersensitivity independently, and this effect was synergistically enhanced by activated EGCs. We conclude that EGC-enteric nerve unit may be involved in IBS-like visceral hypersensitivity, and this process is likely initiated by BDNF-TrkB pathway activation. PMID:26837784

Collateral Ventilation Quantification Using Xenon-Enhanced Dynamic Dual-Energy CT: Differences between Canine and Swine Models of Bronchial Occlusion.

PubMed

Park, Eun-Ah; Goo, Jin Mo; Park, Sang Joon; Lee, Chang Hyun; Park, Chang Min

2015-01-01

The aim of this study was to evaluate whether the difference in the degree of collateral ventilation between canine and swine models of bronchial obstruction could be detected by using xenon-enhanced dynamic dual-energy CT. Eight mongrel dogs and six pigs underwent dynamic dual-energy scanning of 64-slice dual-source CT at 12-second interval for 2-minute wash-in period (60% xenon) and at 24-second interval for 3-minute wash-out period with segmental bronchus occluded. Ventilation parameters of magnitude (A value), maximal slope, velocity (K value), and time-to-peak (TTP) enhancement were calculated from dynamic xenon maps using exponential function of Kety model. A larger difference in A value between parenchyma was observed in pigs than in dogs (absolute difference, -33.0 ± 5.0 Hounsfield units [HU] vs. -2.8 ± 7.1 HU, p = 0.001; normalized percentage difference, -79.8 ± 1.8% vs. -5.4 ± 16.4%, p = 0.0007). Mean maximal slopes in both periods in the occluded parenchyma only decreased in pigs (all p < 0.05). K values of both periods were not different (p = 0.892) in dogs. However, a significant (p = 0.027) difference was found in pigs in the wash-in period. TTP was delayed in the occluded parenchyma in pigs (p = 0.013) but not in dogs (p = 0.892). Xenon-ventilation CT allows the quantification of collateral ventilation and detection of differences between canine and swine models of bronchial obstruction.

Collateral Ventilation Quantification Using Xenon-Enhanced Dynamic Dual-Energy CT: Differences between Canine and Swine Models of Bronchial Occlusion

PubMed Central

Park, Eun-Ah; Park, Sang Joon; Lee, Chang Hyun; Park, Chang Min

2015-01-01

Objective The aim of this study was to evaluate whether the difference in the degree of collateral ventilation between canine and swine models of bronchial obstruction could be detected by using xenon-enhanced dynamic dual-energy CT. Materials and Methods Eight mongrel dogs and six pigs underwent dynamic dual-energy scanning of 64-slice dual-source CT at 12-second interval for 2-minute wash-in period (60% xenon) and at 24-second interval for 3-minute wash-out period with segmental bronchus occluded. Ventilation parameters of magnitude (A value), maximal slope, velocity (K value), and time-to-peak (TTP) enhancement were calculated from dynamic xenon maps using exponential function of Kety model. Results A larger difference in A value between parenchyma was observed in pigs than in dogs (absolute difference, -33.0 ± 5.0 Hounsfield units [HU] vs. -2.8 ± 7.1 HU, p = 0.001; normalized percentage difference, -79.8 ± 1.8% vs. -5.4 ± 16.4%, p = 0.0007). Mean maximal slopes in both periods in the occluded parenchyma only decreased in pigs (all p < 0.05). K values of both periods were not different (p = 0.892) in dogs. However, a significant (p = 0.027) difference was found in pigs in the wash-in period. TTP was delayed in the occluded parenchyma in pigs (p = 0.013) but not in dogs (p = 0.892). Conclusion Xenon-ventilation CT allows the quantification of collateral ventilation and detection of differences between canine and swine models of bronchial obstruction. PMID:25995696

Bone Density Development of the Temporal Bone Assessed by Computed Tomography.

PubMed

Takahashi, Kuniyuki; Morita, Yuka; Ohshima, Shinsuke; Izumi, Shuji; Kubota, Yamato; Horii, Arata

2017-12-01

The temporal bone shows regional differences in bone development. The spreading pattern of acute mastoiditis shows age-related differences. In infants, it spreads laterally and causes retroauricular swelling, whereas in older children, it tends to spread medially and causes intracranial complications. We hypothesized that bone maturation may influence the spreading pattern of acute mastoiditis. Eighty participants with normal hearing, aged 3 months to 42 years, participated in this study. Computed tomography (CT) values (Hounsfield unit [HU]) in various regions of the temporal bone, such as the otic capsule (OC), lateral surface of the mastoid cavity (LS), posterior cranial fossa (PCF), and middle cranial fossa (MCF), were measured as markers of bone density. Bone density development curves, wherein CT values were plotted against age, were created for each region. The age at which the CT value exceeded 1000 HU, which is used as an indicator of bone maturation, was calculated from the development curves and compared between the regions. The OC showed mature bone at birth, whereas the LS, PCF, and MCF showed rapid maturation in early childhood. However, there were significant regional differences in the ages of maturation: 1.7, 3.9, and 10.8 years for the LS, PCF, and MCF, respectively. To our knowledge, this is the first report to show regional differences in the maturation of temporal bone, which could partly account for the differences in the spreading pattern of acute mastoiditis in individuals of different ages.

SU-F-R-56: Early Assessment of Treatment Response During Radiation Therapy Delivery for Esophageal Cancer Using Quantitative CT

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, D; Chen, X; Li, X

2016-06-15

Purpose: To investigate the feasibility of assessing treatment response using CTs during delivery of radiation therapy (RT) for esophageal cancer. Methods: Daily CTs acquired using a CT-on-Rails during the routine CT-guided RT for 20 patients with stage II to IV esophageal cancers were analyzed. All patients were treated with combined chemotherapy and IMRT of 45–50 Gy in 25 fractions, and were followed up for two years. Contours of GTV, spinal cord, and non-specified tissue (NST) irradiated with low dose were generated on each daily CT. A series of CT-texture metrics including Hounsfield Unit (HU) histogram, mean HU, standard derivation (STD),more » entropy, and energy were obtained in these contours on each daily CT. The changes of these metrics and GTV volume during RT delivery were calculated and correlated with treatment outcome. Results: Changes in CT texture (e.g., HU histogram) in GTV and spinal cord (but not in NST) were observed during RT delivery and were consistently increased with radiation dose. For the 20 cases studied, the mean HU in GTV was reduced on average by 4.0HU from the first to the last fractions, while 8 patients (responders) had larger reductions in GTV mean HU (average 7.8 HU) with an average GTV reduction of 51% and had increased consistently in GTV STD and entropy with radiation dose. The rest of 12 patients (non-responders) had lower reductions in GTV mean HU (average 1.5HU) and almost no change in STD and entropy. For the 8 responders, 2 experienced complete response, 7 (88%) survived and 1 died. In contrast, for the 12 non-responders, 4 (33%) survived and 8 died. Conclusion: Radiation can induce changes in CT texture in tumor (e.g., mean HU) during the delivery of RT for esophageal cancer. If validated with more data, such changes may be used for early prediction of RT response for esophageal cancer.« less

Effects of Nandrolone in the Counteraction of Skeletal Muscle Atrophy in a Mouse Model of Muscle Disuse: Molecular Biology and Functional Evaluation

PubMed Central

Camerino, Giulia Maria; Desaphy, Jean-François; De Bellis, Michela; Capogrosso, Roberta Francesca; Cozzoli, Anna; Dinardo, Maria Maddalena; Caloiero, Roberta; Musaraj, Kejla; Fonzino, Adriano; Conte, Elena; Jagerschmidt, Catherine; Namour, Florence; Liantonio, Antonella; De Luca, Annamaria; Conte Camerino, Diana; Pierno, Sabata

2015-01-01

Muscle disuse produces severe atrophy and a slow-to-fast phenotype transition in the postural Soleus (Sol) muscle of rodents. Antioxidants, amino-acids and growth factors were ineffective to ameliorate muscle atrophy. Here we evaluate the effects of nandrolone (ND), an anabolic steroid, on mouse skeletal muscle atrophy induced by hindlimb unloading (HU). Mice were pre-treated for 2-weeks before HU and during the 2-weeks of HU. Muscle weight and total protein content were reduced in HU mice and a restoration of these parameters was found in ND-treated HU mice. The analysis of gene expression by real-time PCR demonstrates an increase of MuRF-1 during HU but minor involvement of other catabolic pathways. However, ND did not affect MuRF-1 expression. The evaluation of anabolic pathways showed no change in mTOR and eIF2-kinase mRNA expression, but the protein expression of the eukaryotic initiation factor eIF2 was reduced during HU and restored by ND. Moreover we found an involvement of regenerative pathways, since the increase of MyoD observed after HU suggests the promotion of myogenic stem cell differentiation in response to atrophy. At the same time, Notch-1 expression was down-regulated. Interestingly, the ND treatment prevented changes in MyoD and Notch-1 expression. On the contrary, there was no evidence for an effect of ND on the change of muscle phenotype induced by HU, since no effect of treatment was observed on the resting gCl, restCa and contractile properties in Sol muscle. Accordingly, PGC1α and myosin heavy chain expression, indexes of the phenotype transition, were not restored in ND-treated HU mice. We hypothesize that ND is unable to directly affect the phenotype transition when the specialized motor unit firing pattern of stimulation is lacking. Nevertheless, through stimulation of protein synthesis, ND preserves protein content and muscle weight, which may result advantageous to the affected skeletal muscle for functional recovery. PMID:26066046

Recognition of Histo-Blood Group Antigen-Like Carbohydrates in Lettuce by Human GII.4 Norovirus

PubMed Central

Gao, Xiang; Esseili, Malak A.; Lu, Zhongyan; Saif, Linda J.

2016-01-01

ABSTRACT Human norovirus (HuNoV) genogroup II genotype 4 (GII.4) strains account for about 80% of the gastroenteritis outbreaks in the United States. Contaminated food is a major transmission vehicle for this virus. In humans, pigs, and oysters, histo-blood group antigens (HBGAs) act as attachment factors for HuNoVs. In lettuce, although the virus-like particles (VLPs) of a GII.4 HuNoV were found to bind to cell wall carbohydrates, the exact binding site has not been investigated. Here, we show the presence of HBGA-like carbohydrates in the cell wall of lettuce. The digestion of lettuce leaves with cell wall-degrading enzymes exposed more binding sites and significantly increased the level of binding of GII.4 HuNoV VLPs. Competition assays showed that both the HBGA monoclonal antibody, recognizing the H type, and plant lectins, recognizing α-l-fucose in the H type, effectively inhibited VLP binding to lettuce tissues. Lettuce cell wall components were isolated and their NoV VLP binding characteristics were tested by enzyme-linked immunosorbent assays. The binding was inhibited by pretreatment of the lettuce cell wall materials with α-1,2-fucosidase. Collectively, our results indicate that H-type HBGA-like carbohydrates exist in lettuce tissues and that GII.4 HuNoV VLPs can bind the exposed fucose moiety, possibly in the hemicellulose component of the cell wall. IMPORTANCE Salad crops and fruits are increasingly recognized as vehicles for human norovirus (HuNoV) transmission. A recent study showed that HuNoVs specifically bind to the carbohydrates of the lettuce cell wall. Histo-blood group antigens (HBGAs) are carbohydrates and are known as the attachment factors for HuNoV infection in humans. In this study, we show the presence of HBGA-like carbohydrates in lettuce, to which HuNoVs specifically bind. These results suggest that specifically bound HuNoVs cannot be removed by simple washing, which may allow viral transmission to consumers. Our findings provide new information needed for developing potential inhibitors to block binding and prevent contamination. PMID:26969699

Recognition of Histo-Blood Group Antigen-Like Carbohydrates in Lettuce by Human GII.4 Norovirus.

PubMed

Gao, Xiang; Esseili, Malak A; Lu, Zhongyan; Saif, Linda J; Wang, Qiuhong

2016-05-15

Human norovirus (HuNoV) genogroup II genotype 4 (GII.4) strains account for about 80% of the gastroenteritis outbreaks in the United States. Contaminated food is a major transmission vehicle for this virus. In humans, pigs, and oysters, histo-blood group antigens (HBGAs) act as attachment factors for HuNoVs. In lettuce, although the virus-like particles (VLPs) of a GII.4 HuNoV were found to bind to cell wall carbohydrates, the exact binding site has not been investigated. Here, we show the presence of HBGA-like carbohydrates in the cell wall of lettuce. The digestion of lettuce leaves with cell wall-degrading enzymes exposed more binding sites and significantly increased the level of binding of GII.4 HuNoV VLPs. Competition assays showed that both the HBGA monoclonal antibody, recognizing the H type, and plant lectins, recognizing α-l-fucose in the H type, effectively inhibited VLP binding to lettuce tissues. Lettuce cell wall components were isolated and their NoV VLP binding characteristics were tested by enzyme-linked immunosorbent assays. The binding was inhibited by pretreatment of the lettuce cell wall materials with α-1,2-fucosidase. Collectively, our results indicate that H-type HBGA-like carbohydrates exist in lettuce tissues and that GII.4 HuNoV VLPs can bind the exposed fucose moiety, possibly in the hemicellulose component of the cell wall. Salad crops and fruits are increasingly recognized as vehicles for human norovirus (HuNoV) transmission. A recent study showed that HuNoVs specifically bind to the carbohydrates of the lettuce cell wall. Histo-blood group antigens (HBGAs) are carbohydrates and are known as the attachment factors for HuNoV infection in humans. In this study, we show the presence of HBGA-like carbohydrates in lettuce, to which HuNoVs specifically bind. These results suggest that specifically bound HuNoVs cannot be removed by simple washing, which may allow viral transmission to consumers. Our findings provide new information needed for developing potential inhibitors to block binding and prevent contamination. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Effects of Nandrolone in the Counteraction of Skeletal Muscle Atrophy in a Mouse Model of Muscle Disuse: Molecular Biology and Functional Evaluation.

PubMed

Camerino, Giulia Maria; Desaphy, Jean-François; De Bellis, Michela; Capogrosso, Roberta Francesca; Cozzoli, Anna; Dinardo, Maria Maddalena; Caloiero, Roberta; Musaraj, Kejla; Fonzino, Adriano; Conte, Elena; Jagerschmidt, Catherine; Namour, Florence; Liantonio, Antonella; De Luca, Annamaria; Conte Camerino, Diana; Pierno, Sabata

2015-01-01

Muscle disuse produces severe atrophy and a slow-to-fast phenotype transition in the postural Soleus (Sol) muscle of rodents. Antioxidants, amino-acids and growth factors were ineffective to ameliorate muscle atrophy. Here we evaluate the effects of nandrolone (ND), an anabolic steroid, on mouse skeletal muscle atrophy induced by hindlimb unloading (HU). Mice were pre-treated for 2-weeks before HU and during the 2-weeks of HU. Muscle weight and total protein content were reduced in HU mice and a restoration of these parameters was found in ND-treated HU mice. The analysis of gene expression by real-time PCR demonstrates an increase of MuRF-1 during HU but minor involvement of other catabolic pathways. However, ND did not affect MuRF-1 expression. The evaluation of anabolic pathways showed no change in mTOR and eIF2-kinase mRNA expression, but the protein expression of the eukaryotic initiation factor eIF2 was reduced during HU and restored by ND. Moreover we found an involvement of regenerative pathways, since the increase of MyoD observed after HU suggests the promotion of myogenic stem cell differentiation in response to atrophy. At the same time, Notch-1 expression was down-regulated. Interestingly, the ND treatment prevented changes in MyoD and Notch-1 expression. On the contrary, there was no evidence for an effect of ND on the change of muscle phenotype induced by HU, since no effect of treatment was observed on the resting gCl, restCa and contractile properties in Sol muscle. Accordingly, PGC1α and myosin heavy chain expression, indexes of the phenotype transition, were not restored in ND-treated HU mice. We hypothesize that ND is unable to directly affect the phenotype transition when the specialized motor unit firing pattern of stimulation is lacking. Nevertheless, through stimulation of protein synthesis, ND preserves protein content and muscle weight, which may result advantageous to the affected skeletal muscle for functional recovery.

Influence of fixed muscle length and contractile properties on atrophy and subsequent recovery in the rat soleus and plantaris muscles.

PubMed

Fujita, Naoto; Arakawa, Takamitsu; Matsubara, Takako; Ando, Hiroshi; Miki, Akinori

2009-01-01

This study examined muscular atrophy and the recovery process induced by hindlimb unloading and joint immobilization in the rat soleus and plantaris muscles. Rats were divided into control, hindlimb unloading (HU), hindlimb unloading with ankle joint immobilization at the maximum dorsiflexion (HUD), and maximum plantarflexion (HUP) groups. The hindlimb was reloaded after fourteen days of unloading, and muscle atrophy and walking ability were assessed at 0, 3, and 7 days of reloading. A cross sectional area of muscle fibers in the soleus muscle on day 0 of reloading revealed sizes in order from the control, HUD, HUP down to the HU group, indicating that the HU group was the most atrophied among the four groups. These values in the plantaris muscle ranged in order from the control, HU, HUD, to HUP groups, the HUP group being the most atrophied among the four groups. These muscles recovered from atrophy in the same descending order, and the values in the HUD and HUP groups slowly recovered during the reloading periods. The HUD and HUP groups showed a central core lesion and reloading-induced lesions in some type I muscle fibers after the immobilization and reloading, one possible reason for the delayed recovery in these groups. The muscle atrophy in the HU, HUD, and HUP groups remained at day 7 although the walking ability appeared to be normal. Accordingly, further rehabilitation therapy might be necessary even if the functional ability appears to be normal.

Image-based metal artifact reduction in x-ray computed tomography utilizing local anatomical similarity

NASA Astrophysics Data System (ADS)

Dong, Xue; Yang, Xiaofeng; Rosenfield, Jonathan; Elder, Eric; Dhabaan, Anees

2017-03-01

X-ray computed tomography (CT) is widely used in radiation therapy treatment planning in recent years. However, metal implants such as dental fillings and hip prostheses can cause severe bright and dark streaking artifacts in reconstructed CT images. These artifacts decrease image contrast and degrade HU accuracy, leading to inaccuracies in target delineation and dose calculation. In this work, a metal artifact reduction method is proposed based on the intrinsic anatomical similarity between neighboring CT slices. Neighboring CT slices from the same patient exhibit similar anatomical features. Exploiting this anatomical similarity, a gamma map is calculated as a weighted summation of relative HU error and distance error for each pixel in an artifact-corrupted CT image relative to a neighboring, artifactfree image. The minimum value in the gamma map for each pixel is used to identify an appropriate pixel from the artifact-free CT slice to replace the corresponding artifact-corrupted pixel. With the proposed method, the mean CT HU error was reduced from 360 HU and 460 HU to 24 HU and 34 HU on head and pelvis CT images, respectively. Dose calculation accuracy also improved, as the dose difference was reduced from greater than 20% to less than 4%. Using 3%/3mm criteria, the gamma analysis failure rate was reduced from 23.25% to 0.02%. An image-based metal artifact reduction method is proposed that replaces corrupted image pixels with pixels from neighboring CT slices free of metal artifacts. This method is shown to be capable of suppressing streaking artifacts, thereby improving HU and dose calculation accuracy.

The interaction of hydroxyurea and ionizing radiation in human cervical carcinoma cells.

PubMed

Kuo, M L; Kunugi, K A; Lindstrom, M J; Kinsella, T J

1997-01-01

The results from prior in vitro and in vivo studies and recent phase 3 clinical trials suggest a significant potential role for hydroxyurea (HU) as a clinical radiosensitizer for cervix cancer. However, a detailed study of possible cellular mechanisms of radiosensitization in human cervix cancer cells as a consequence of dose and timing of HU and ionizing radiation (IR) has not been performed. This in vitro study analyses the interactions of HU and IR in a human cervical carcinoma cell line, Caski. Exponentially growing Caski cells were continuously exposed to clinically achievable but minimally cytotoxic concentrations of HU (0.3-3.0 mM) for various time intervals (6, 12, 18, 24, and 30 hours) up to one population doubling time either prior to or immediately following IR (2-8 Gy). The radiation survival data were analyzed using our modification of the linear-quadratic model to test for an interaction (greater than additive). The effects of HU alone, IR alone, and the combination on cell cycle progression and on apoptotic cell death in exponentially growing Caski cells were measured. We report a significant HU-IR interaction (radiosensitization) based on the sequence of HU exposure (post- > pre-IR) and with increasing concentrations of HU (0.3-3.0 mM), but no effect on radiosensitization with the duration of exposure to HU for up to one cell population doubling (6-30 hours). HU concentration has a significant effect on both alpha and beta linear-quadratic values in the post-IR sequences. Exposures of exponentially growing Caski cells to 1 mM and 3 mM HU alone result in a complete block in early S phase throughout the 30-hour exposure, while 0.3 mM HU causes a transient early S-phase block over the initial 12 to 18 hours of exposure. HU alone has no effect on cell cycle progression in G1 or G2/M populations but results in a large apoptotic population (31% following 1 mM HU x 30 hours), which appears to be the principal mechanism of drug cytotoxicity in these cells. IR alone (4 or 6 Gy) results in a significant G2 delay for 6 to 18 hours following IR but no G1 delay and a small apoptotic population at 30 hours post-IR (5.4% vs 2.1% in non-IR controls). The use of HU (0.3 or 1.0 mM) following IR (4 or 6 Gy) results in a significantly larger G2 delay compared with IR alone, but with only an additive effect on the apoptotic population. These in vitro data demonstrate that radiosensitization of Caski cells is more significant with post-IR exposures to clinically achievable concentrations of HU. This HU-IR interaction is associated with an increased G2 delay, suggesting a reduction in IR damage repair. However, this interaction appears to be independent of the cytotoxicity (principally by apoptosis) from HU alone.

Deriving Hounsfield units using grey levels in cone beam computed tomography

PubMed Central

Mah, P; Reeves, T E; McDavid, W D

2010-01-01

Objectives An in vitro study was performed to investigate the relationship between grey levels in dental cone beam CT (CBCT) and Hounsfield units (HU) in CBCT scanners. Methods A phantom containing 8 different materials of known composition and density was imaged with 11 different dental CBCT scanners and 2 medical CT scanners. The phantom was scanned under three conditions: phantom alone and phantom in a small and large water container. The reconstructed data were exported as Digital Imaging and Communications in Medicine (DICOM) and analysed with On Demand 3D® by Cybermed, Seoul, Korea. The relationship between grey levels and linear attenuation coefficients was investigated. Results It was demonstrated that a linear relationship between the grey levels and the attenuation coefficients of each of the materials exists at some “effective” energy. From the linear regression equation of the reference materials, attenuation coefficients were obtained for each of the materials and CT numbers in HU were derived using the standard equation. Conclusions HU can be derived from the grey levels in dental CBCT scanners using linear attenuation coefficients as an intermediate step. PMID:20729181

DOE Office of Scientific and Technical Information (OSTI.GOV)

Korhonen, Juha, E-mail: juha.p.korhonen@hus.fi; Kapanen, Mika; Department of Oncology, Helsinki University Central Hospital, POB-180, 00029 HUS

Purpose: The lack of electron density information in magnetic resonance images (MRI) poses a major challenge for MRI-based radiotherapy treatment planning (RTP). In this study the authors convert MRI intensity values into Hounsfield units (HUs) in the male pelvis and thus enable accurate MRI-based RTP for prostate cancer patients with varying tissue anatomy and body fat contents. Methods: T{sub 1}/T{sub 2}*-weighted MRI intensity values and standard computed tomography (CT) image HUs in the male pelvis were analyzed using image data of 10 prostate cancer patients. The collected data were utilized to generate a dual model HU conversion technique from MRImore » intensity values of the single image set separately within and outside of contoured pelvic bones. Within the bone segment local MRI intensity values were converted to HUs by applying a second-order polynomial model. This model was tuned for each patient by two patient-specific adjustments: MR signal normalization to correct shifts in absolute intensity level and application of a cutoff value to accurately represent low density bony tissue HUs. For soft tissues, such as fat and muscle, located outside of the bone contours, a threshold-based segmentation method without requirements for any patient-specific adjustments was introduced to convert MRI intensity values into HUs. The dual model HU conversion technique was implemented by constructing pseudo-CT images for 10 other prostate cancer patients. The feasibility of these images for RTP was evaluated by comparing HUs in the generated pseudo-CT images with those in standard CT images, and by determining deviations in MRI-based dose distributions compared to those in CT images with 7-field intensity modulated radiation therapy (IMRT) with the anisotropic analytical algorithm and 360° volumetric-modulated arc therapy (VMAT) with the Voxel Monte Carlo algorithm. Results: The average HU differences between the constructed pseudo-CT images and standard CT images of each test patient ranged from −2 to 5 HUs and from 22 to 78 HUs in soft and bony tissues, respectively. The average local absolute value differences were 11 HUs in soft tissues and 99 HUs in bones. The planning target volume doses (volumes 95%, 50%, 5%) in the pseudo-CT images were within 0.8% compared to those in CT images in all of the 20 treatment plans. The average deviation was 0.3%. With all the test patients over 94% (IMRT) and 92% (VMAT) of dose points within body (lower than 10% of maximum dose suppressed) passed the 1 mm and 1% 2D gamma index criterion. The statistical tests (t- and F-tests) showed significantly improved (p ≤ 0.05) HU and dose calculation accuracies with the soft tissue conversion method instead of homogeneous representation of these tissues in MRI-based RTP images. Conclusions: This study indicates that it is possible to construct high quality pseudo-CT images by converting the intensity values of a single MRI series into HUs in the male pelvis, and to use these images for accurate MRI-based prostate RTP dose calculations.« less

Multilineage hematopoietic recovery by a single injection of pegylated recombinant human megakaryocyte growth and development factor in myelosuppressed mice.

PubMed

Shibuya, K; Akahori, H; Takahashi, K; Tahara, E; Kato, T; Miyazaki, H

1998-01-01

Previous studies have shown that daily multiple administration of pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF) markedly stimulates thrombopoiesis and effectively ameliorates thrombocytopenia, and in most cases anemia and neutropenia, in myelosuppressed animals. In this study, we evaluated the effects of a single intravenous injection of PEG-rHuMGDF on hematopoietic recovery after sublethal total-body irradiation in mice. A single injection of PEG-rHuMGDF (1 to 640 microg/kg) 1 hour after irradiation accelerated platelet, red blood cell (RBC), and white blood cell (WBC) recovery in a dose-dependent fashion. In the bone marrow of vehicle-treated mice, megakaryocytic, erythroid, and myeloid progenitors, as well as day 12 colony-forming unit-spleen (CFU-S), were dramatically decreased much earlier than the nadirs of peripheral blood cells, whereas megakaryocytes were modestly decreased. Treatment with PEG-rHuMGDF (80 microg/kg, an optimal dose) 1 hour after irradiation resulted in more rapid recovery of these four hematopoietic progenitors and also significantly facilitated megakaryocyte recovery. In addition, the same PEG-rHuMGDF administration schedule expanded bone marrow cells capable of rescuing lethally irradiated recipient mice. As the interval between irradiation and PEG-rHuMGDF treatment was longer, its effects on hematopoietic recovery were attenuated. In contrast to the effects of PEG-rHuMGDF, a single injection of recombinant human granulocyte colony-stimulating factor (rhG-CSF) 1 hour after irradiation exclusively accelerated WBC recovery, but only to a similar extent as PEG-rHuMGDF (80 microg/kg) treatment even when rhG-CSF doses were escalated to 1,000 microg/kg. This appeared related to different pharmacokinetics of these two factors after a single injection in irradiated mice. The concentrations of PEG-rHuMGDF after injection persisted in the plasma for a longer time compared with rhG-CSF. These results indicate that a single injection of PEG-rHuMGDF at an early time after irradiation is able to effectively improve thrombocytopenia, anemia, and leukopenia with concomitant accelerated recovery of both primitive and committed hematopoietic progenitors in irradiated mice. Our data also show that compared with the rhG-CSF shown to exert multilineage effects on hematopoiesis, PEG-rHuMGDF has more wide-ranging effects on peripheral blood cell recovery.

Patient size and x-ray technique factors in head computed tomography examinations. II. Image quality.

PubMed

Huda, Walter; Lieberman, Kristin A; Chang, Jack; Roskopf, Marsha L

2004-03-01

We investigated how patient head characteristics, as well as the choice of x-ray technique factors, affect lesion contrast and noise values in computed tomography (CT) images. Head sizes and mean Hounsfield unit (HU) values were obtained from head CT images for five classes of patients ranging from the newborn to adults. X-ray spectra with tube voltages ranging from 80 to 140 kV were used to compute the average photon energy, and energy fluence, transmitted through the heads of patients of varying size. Image contrast, and the corresponding contrast to noise ratios (CNRs), were determined for lesions of fat, muscle, and iodine relative to a uniform water background. Maintaining a constant image CNR for each lesion, the patient energy imparted was also computed to identify the x-ray tube voltage that minimized the radiation dose. For adults, increasing the tube voltage from 80 to 140 kV changed the iodine HU from 2.62 x 10(5) to 1.27 x 10(5), the fat HU from -138 to -108, and the muscle HU from 37.1 to 33.0. Increasing the x-ray tube voltage from 80 to 140 kV increased the percentage energy fluence transmission by up to a factor of 2. For a fixed x-ray tube voltage, the percentage transmitted energy fluence in adults was more than a factor of 4 lower than for newborns. For adults, increasing the x-ray tube voltage from 80 to 140 kV improved the CNR for muscle lesions by 130%, for fat lesions by a factor of 2, and for iodine lesions by 25%. As the size of the patient increased from newborn to adults, lesion CNR was reduced by about a factor of 2. The mAs value can be reduced by 80% when scanning newborns while maintaining the same lesion CNR as for adults. Maintaining the CNR of an iodine lesion at a constant level, use of 140 kV increases the energy imparted to an adult patient by nearly a factor of 3.5 in comparison to 80 kV. For fat and muscle lesions, raising the x-ray tube voltage from 80 to 140 kV at a constant CNR increased the patient dose by 37% and 7%, respectively. Our two key findings are that for head CT examinations performed at a constant CNR, the mAs can be substantially reduced when scanning infants, and that use of the lowest x-ray tube voltage will generally reduce patient doses.

Clinical and radiological investigations of mandibular overdentures supported by conventional or mini-dental implants: A 2-year prospective follow-up study.

PubMed

Temizel, Sonay; Heinemann, Friedhelm; Dirk, Cornelius; Bourauel, Christoph; Hasan, Istabrak

2017-02-01

Conventional dental implants are not applicable in the mandibular interforaminal region if bone volume is limited. Mini-dental implants offer an alternative means of supporting mandibular overdentures in a narrow residual ridge, without additional surgery. The purpose of this nonrandomized clinical trial was to compare the ability of mini-dental implants with that of conventional dental implants in supporting mandibular overdentures during a 2-year clinical follow-up. Bone quality, bone resorption, implant stability, and oral health were assessed radiographically. A total of 32 participants with edentulism were included. Twenty-two participants (99 implants) received 4 to 5 mini-dental implants (diameter: 1.8-2.4 mm; length: 13-15 mm, study group), and 10 participants (35 implants) received 2 to 4 conventional dental implants (diameter: 3.3-3.7 mm; length: 11-13 mm, control group). The selection of the participants in the study or control group was based on the available bone volume in the mandible. The selection was not randomized. The density of cortical bone thickness was measured in Hounsfield units (HU) from computed tomography data, and patients were followed for 2 years. The participants were examined 3, 6, 12, and 24 months after surgery. Primary stability immediately after the insertion of dental implants (Periotest), secondary stability 6 months after implantation, modified plaque, bleeding on probing indices, and probing depth were measured and analyzed statistically (α=.05). The mean HU value 6 months after implantation in the participants who received mini-dental implants was significantly (P=.035) higher (1250 HU) than that in the participants who received conventional dental implants (1100 HU). The probing depths around the conventional dental implants (1.6 and 1.8 mm, respectively) were significantly higher than those around the mini-dental implants (1.3 and 1.2 mm, respectively) 12 and 24 months after surgery, respectively (P<.001). The mean primary and secondary stability values for conventional dental implants were -4.0 and -4.9, respectively. The primary and secondary stability values for the mini-dental implants were -0.3 and -1.4, respectively. The Periotest values of the primary (measured immediately after implant insertion) and secondary implant stabilities (measured 6 months after implant insertion) were significantly higher for the conventional dental implants than for the mini-dental implants (P<.001). Based on this 2-year clinical trial, patients receiving mini-dental implants had clinical outcomes similar to those of patients receiving conventional dental implants to support overdenture prostheses. Copyright © 2016 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.

Computed tomography imaging for the characterisation of drugs with radiation density measurements and HU spectroscopy.

PubMed

Sieron, Dominik A; Steib, Moritz; Suter, Dominik; Obmann, Verena C; Huber, Adrian T; Ebner, Lukas; Inderbitzin, Daniel; Christe, Andreas

2018-01-29

To investigate the computed tomography (CT) density of frequently administered medications (1) for the better characterisation of substances on abdominal CT, (2) to allow radiologists to narrow down possibilities in the identification of hyperdense material in the bowel and (3) to provide forensic doctors with a tool to identify gastric contents before an autopsy. From the list of the local hospital pharmacy, the 50 most frequently used medications were identified and scanned twice with a 128 row CT scanner (Acquillion, Toshiba, Tokyo, Japan). The protocol comprised two tube voltages of 100 kVp and 120 kVp, with a tube current of 100 mAs, a collimation of 0.5 mm and a slice thickness of 0.5 mm. Two readers were asked to measure the density (in Hounsfield units) and the noise (standard deviation of the Hounsfield units) of each pill in the two scans (100/120 kVp). After 4 weeks, both readers repeated the measurements to test repeatability (intra-rater agreement). The behaviour of each pill in hydrochloric acid (pH 2) was examined and the dissolution time was determined. The most dense pill was Cordarone (7265 HU), and the least was Perenterol (529 HU), with an attenuation that was lower than fat density (<120 HU). The standard deviation of pixel density (noise) reflects inhomogeneity of the pharmacological product, varying from 9 to 1592 HU among the different pills (at 120 kVp). The absolute average HU increase per pill when changing to lower voltage was 78 ± 253 HU, with a linear fitting line with a slope of 0.21 as a constant variable in the density spectroscopy. After 4 hours in hydrochloric acid, only six tablets were still intact, including Flagyl and Dafalgan. The intra- and inter-rater agreements for all measurements were nearly perfect, with a correlation coefficient r of ≥0.99 (p <0.0001). Our data suggest that measuring the attenuation of drugs on CT images, including the homogeneity, and applying CT spectroscopy can narrow down possible identities of the most frequently medications. Other clinicians and forensic pathologists can perform this easy measurement, as the intra- and inter-reader variability is very small.

Differentiation of Ductal Carcinoma In-Situ from Benign Micro-Calcifications by Dedicated Breast Computed Tomography

PubMed Central

Shakeri, Shadi A.; Abbey, Craig K.; Gazi, Peymon; Prionas, Nicolas; Nosratieh, Anita; Li, Chin-Shang; Boone, John M.; Lindfors, Karen K.

2015-01-01

Purpose Compare conspicuity of ductal carcinoma in-situ (DCIS) to benign calcifications on unenhanced (bCT), contrast-enhanced dedicated breast CT (CEbCT) and mammography (DM). Methods and Materials The institutional review board approved this HIPAA-compliant study. 42 women with Breast Imaging Reporting and Data System 4 or 5 category micro-calcifications had breast CT before biopsy. Three subjects with invasive disease at surgery were excluded. Two breast radiologists independently compared lesion conspicuity scores (CS) for CEbCT, to bCT and DM. Enhancement was measured in Hounsfield units (HU). Mean CS ± standard deviations are shown. Receiver operating characteristic analysis (ROC) measured radiologists’ discrimination performance by comparing CS to enhancement alone. Statistical measurements were made using ANOVA F-test, Wilcoxon rank-sum test and robust linear regression analyses. Results 39 lesions (17 DCIS, 22 benign) were analyzed. DCIS (8.5±0.9, n=17) was more conspicuous than benign micro-calcifications (3.6±2.9, n=22; p<0.0001) on CEbCT. DCIS was equally conspicuous on CEbCT and DM (8.5±0.9, 8.7±0.8, n=17; p=0.85) and more conspicuous when compared to bCT (5.3±2.6, n=17; p<0.001). All DCIS enhanced; mean enhancement (90HU ±53HU, n=17) was higher compared to benign lesions (33 ±30HU, n=22)(p<0.0001). ROC analysis of the radiologists’ CS showed high discrimination performance (AUC=0.94) compared to enhancement alone (AUC=0.85) (p<0.026). Conclusion DCIS is more conspicuous than benign micro-calcifications on CEbCT. DCIS visualization on CEbCT is equal to mammography but improved compared to bCT. Radiologists’ discrimination performance using CEBCT is significantly higher than enhancement values alone. CEbCT may have an advantage over mammography by reducing false positive examinations when calcifications are analyzed. PMID:26520874

Effects of different tube potentials and iodine concentrations on image enhancement, contrast-to-noise ratio and noise in micro-CT images: a phantom study

PubMed Central

Shaffiq Said Rahmat, Said Mohd; Md Saad, Wan Mazlina

2013-01-01

The study aimed to investigate the effects of different tube potentials and concentrations of iodinated contrast media (CM) on the image enhancement, contrast-to-noise ratio (CNR) and noise in micro-computed tomography (µCT) images. A phantom containing of five polyethylene tube was filled with 2 mL of deionized water and iodinated CM (Omnipaque 300 mgI/mL) at four different concentrations: 5, 10, 15, and 20 mol/L, respectively. The phantom was scanned with a µCT machine (SkyScan 1176) using various tube potentials: 40, 50, 60, 70, 80, and 90 kVp, a fixed tube current; 100 µA, and filtration of 0.2 mm aluminum (Al). The percentage difference of image enhancement, CNR and noise of all images, acquired at different kVps and concentrations, were calculated. The image enhancement, CNR and noise curves with respect to tube potential and concentration were plotted and analysed. The highest image enhancement was found at the lowest tube potential of 40 kVp. At this kVp setting, the percentage difference of image enhancement [Hounsfield Unit (HU) of 20 mol/L iodine concentration over HU of deionized water] was 43%. By increasing the tube potential, it resulted with the reduction of HU, where only 17.5% different were noticed for 90 kVp. Across all iodine concentrations (5-20 M), CNR peaked at 80 kVp and then these values showed a slight decreasing pattern, which might be due insufficient tube current compensation. The percentage difference of image noise obtained at 40 and 90 kVp was 72.4%. Lower tube potential setting results in higher image enhancement (HU) in conjunction with increasing concentration of iodinated CM. Overall, the tube potential increment will substantially improve CNR and reduce image noise. PMID:24273743

Fluid tagging for CT colonography: effectiveness of a 2-hour iodinated oral preparation after incomplete optical colonoscopy.

PubMed

Chang, Kevin J; Rekhi, Satinder S; Anderson, Stephan W; Soto, Jorge A

2011-01-01

To evaluate the distal extent and attenuation of bowel opacification achieved after administration of a single low volume dose of oral contrast 2 hours before computed tomographic colonography (CTC) after incomplete optical colonoscopy. This retrospective study included 144 patients undergoing CTC after incomplete colonoscopy from April 2006 to July 2008 at 2 separate medical centers. Each patient received 20 to 30 mL of diatrizoate meglumine and diatrizoate sodium solution 2 hours before being scanned. The distalmost extent of opacification was: stomach/small bowel, n = 13; cecum, n = 2; ascending colon, n = 7; transverse colon, n = 19; descending colon, n = 14; sigmoid colon, n = 24; rectum, n = 65. The mean attenuation of each opacified segment was: cecum, 449 Hounsfield units (HU); ascending colon, 474 HU; transverse colon, 468 HU; descending colon, 421 HU; sigmoid colon, 391 HU; and rectum, 382 HU. In 103 (71.5%) patients, oral contrast reached the distal colon (descending colon, sigmoid colon, or rectum). The oral contrast did not reach the colon in only 13 (9.0%) patients. Oral administration of a small volume hyperosmolar oral contrast agent 2 hours before CTC results in satisfactory colonic opacification in the majority of patients. Adding same-day fluid tagging in incomplete colonoscopy patients presenting for completion CTC should result in adequate fluid opacification for most of the colon, especially proximal segments not visualized at the time of incomplete colonoscopy.

Qualitative and quantitative interpretation of computed tomography of the lungs in healthy neonatal foals.

PubMed

Lascola, Kara M; O'Brien, Robert T; Wilkins, Pamela A; Clark-Price, Stuart C; Hartman, Susan K; Mitchell, Mark A

2013-09-01

To qualitatively describe lung CT images obtained from sedated healthy equine neonates (≤ 14 days of age), use quantitative analysis of CT images to characterize attenuation and distribution of gas and tissue volumes within the lungs, and identify differences between lung characteristics of foals ≤ 7 days of age and foals > 7 days of age. 10 Standardbred foals between 2.5 and 13 days of age. Foals were sedated with butorphanol, midazolam, and propofol and positioned in sternal recumbency for thoracic CT. Image analysis software was used to exclude lung from nonlung structures. Lung attenuation was measured in Hounsfield units (HU) for analysis of whole lung and regional changes in attenuation and lung gas and tissue components. Degree of lung attenuation was classified as follows: hyperinflated or emphysema, -1,000 to -901 HU; well aerated, -900 to -501 HU; poorly aerated, -500 to -101 HU; and nonaerated, > -100 HU. Qualitative evidence of an increase in lung attenuation and patchy alveolar patterns in the ventral lung region were more pronounced in foals ≤ 7 days of age than in older foals. Quantitative analysis revealed that mean ± SD lung attenuation was greater in foals ≤ 7 days of age (-442 ± 28 HU) than in foals > 7 days of age (-521 ± 24 HU). Lung aeration and gas volumes were lower than in other regions ventrally and in the mid lung region caudal to the heart. CONCLUSIONS AND CLINICAL RELEVANCE-Identified radiographic patterns and changes in attenuation were most consistent with atelectasis and appeared more severe in foals ≤ 7 days of age than in older neonatal foals. Recognition of these changes may have implications for accurate CT interpretation in sedated neonatal foals with pulmonary disease.

Development of an in vitro Bioassay for Recombinant Human Erythropoietin (rHuEPO) Based on Proliferative Stimulation of an Erythroid Cell Line and Analysis of Sialic Acid Dependent Microheterogeneity: UT-7 Cell Bioassay.

PubMed

Metta, Manoj Kumar; Malkhed, Vasavi; Tantravahi, Srinivasan; Vuruputuri, Uma; Kunaparaju, Rajkumar

2017-04-01

Determination of biological activity and its comparison with clinical behavior is important in the quality assessment of therapeutic glycoproteins. In vivo studies are usually employed for evaluating bioactivity of these glycomolecules. However, alternative methods are required to simplify the bioassay and avoid ethical issues associated with in vivo studies. Negatively charged sialic acid residues are known to be critical for in vivo bioactivity of rHuEPO. To address this need, we employed the human acute myeloid leukemia cell line UT-7 for the determination of proliferative stimulation induced by rHuEPO. Relative potencies of various intact and sugar-trimmed rHuEPO preparations were estimated using the International Standard for Human r-DNA derived EPO (87/684) as a reference for bioactivity. The cellular response was measured with a multi-channel photometer using a colorimetric microassay, based on the metabolism of the Resazurin sodium by cell viability. For a resourceful probing of physiological features of rHuEPO with significance, we obtained partly or completely desialylated rHuEPO digested by the neuraminidase enzyme without degradation of carbohydrates. Two-fold higher specific activity was shown by asialoerythropoietin in in vitro analysis compared with the sialoerythropoietin. Further, computational studies were also carried out to construct the 3D model of the erythropoietin (EPO) protein structure using standard comparative modeling methods. The quality of the model was validated using Procheck and protein structure analysis (ProSA) server tools. N-glycan units were constructed; moreover, EPO protein was glycosylated at potential glycosylation amino acid residue sites. The method described should be suitable for potency assessments of pharmaceutical formulations of rHuEPO (European Pharmacopeia, 2016).

Temporal changes in physiology and haematology in response to high- and micro-doses of recombinant human erythropoietin.

PubMed

Clark, Brad; Woolford, Sarah M; Eastwood, Annette; Sharpe, Ken; Barnes, Peter G; Gore, Christopher J

2017-10-01

There is evidence to suggest athletes have adopted recombinant human erythropoietin (rHuEPO) dosing regimens that diminish the likelihood of being caught by direct detection techniques. However, the temporal response in physiology, performance, and Athlete Biological Passport (ABP) parameters to such regimens is not clearly understood. Participants were assigned to a high-dose only group (HIGH, n = 8, six rHuEPO doses of 250 IU/kg over two weeks), a combined high micro-dose group (COMB, n = 8, high-dose plus nine rHuEPO micro-doses over a further three weeks), or one of two placebo control groups who received saline in the same pattern as the HIGH (HIGH-PLACEBO, n = 4) or COMB (COMB-PLACEBO, n = 4) groups. Temporal changes in physiology and performance were tracked by graded exercise test (GXT) and haemoglobin mass assessment at baseline, after high dose, after micro-dose (COMB and COMB-PLACEBO only) and after a four-week washout. Venous blood samples were collected throughout the baseline, rHuEPO administration, and washout periods to determine the haematological and ABP response to each dosing regimen. Physiological adaptations induced by a two-week rHuEPO high-dose were maintained by rHuEPO micro-dosing for at least three weeks. However, all participants administered rHuEPO registered at least one suspicious ABP value during the administration or washout periods. These results indicate there is sufficient sensitivity in the ABP to detect use of high rHuEPO doping regimens in athletic populations and they provide important empirical examples for use by anti-doping experts. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Abdominal Imaging with Contrast-enhanced Photon-counting CT: First Human Experience

PubMed Central

Pourmorteza, Amir; Symons, Rolf; Sandfort, Veit; Mallek, Marissa; Fuld, Matthew K.; Henderson, Gregory; Jones, Elizabeth C.; Malayeri, Ashkan A.; Folio, Les R.

2016-01-01

Purpose To evaluate the performance of a prototype photon-counting detector (PCD) computed tomography (CT) system for abdominal CT in humans and to compare the results with a conventional energy-integrating detector (EID). Materials and Methods The study was HIPAA-compliant and institutional review board–approved with informed consent. Fifteen asymptomatic volunteers (seven men; mean age, 58.2 years ± 9.8 [standard deviation]) were prospectively enrolled between September 2 and November 13, 2015. Radiation dose–matched delayed contrast agent–enhanced spiral and axial abdominal EID and PCD scans were acquired. Spiral images were scored for image quality (Wilcoxon signed-rank test) in five regions of interest by three radiologists blinded to the detector system, and the axial scans were used to assess Hounsfield unit accuracy in seven regions of interest (paired t test). Intraclass correlation coefficient (ICC) was used to assess reproducibility. PCD images were also used to calculate iodine concentration maps. Spatial resolution, noise-power spectrum, and Hounsfield unit accuracy of the systems were estimated by using a CT phantom. Results In both systems, scores were similar for image quality (median score, 4; P = .19), noise (median score, 3; P = .30), and artifact (median score, 1; P = .17), with good interrater agreement (image quality, noise, and artifact ICC: 0.84, 0.88, and 0.74, respectively). Hounsfield unit values, spatial resolution, and noise-power spectrum were also similar with the exception of mean Hounsfield unit value in the spinal canal, which was lower in the PCD than the EID images because of beam hardening (20 HU vs 36.5 HU; P < .001). Contrast-to-noise ratio of enhanced kidney tissue was improved with PCD iodine mapping compared with EID (5.2 ± 1.3 vs 4.0 ± 1.3; P < .001). Conclusion The performance of PCD showed no statistically significant difference compared with EID when the abdomen was evaluated in a conventional scan mode. PCD provides spectral information, which may be used for material decomposition. © RSNA, 2016 PMID:26840654

Prevalence of Pancreatic Steatosis at a Pediatric Tertiary Care Center.

PubMed

Pham, Yen H; Bingham, Brigid A; Bell, Cynthia S; Greenfield, Susan A; John, Susan D; Robinson, Lawrence H; Eissa, Mona A

2016-03-01

Pancreatic steatosis in adults has been proposed to be associated with obesity; however, data on pancreatic steatosis in children are lacking. Our study aimed to measure the prevalence of pancreatic steatosis in children and to examine its association with obesity and nonalcoholic fatty liver disease. This is a retrospective chart review study of 232 patients 2 to 18 years old who underwent abdominal computed tomographic imaging in the emergency department or inpatient ward within a 1-year time span and from whom demographics, anthropometrics, and medical history were obtained. Our radiologist determined mean Hounsfield unit (HU) measurements for the pancreas, liver, and spleen. A difference of -20 between the pancreas and spleen (psHU) and between the liver and spleen was used to determine fatty infiltration. Of the 232 patients, 11.5% had a psHU less than -20. The prevalence of pancreatic steatosis was more than double among obese children (19%) than that in nonobese groups (8%). There is a significant correlation between the psHU and liver-spleen HU (r = 0.50, P < 0.001). Pancreatic steatosis was identified in 10% of the study population and is associated with obesity. Also, pancreatic steatosis is significantly associated with nonalcoholic fatty liver disease. This is the first study assessing the prevalence of pancreatic steatosis in children.

Oral health attitudes and behavior of dental students at the University of Zagreb, Croatia.

PubMed

Badovinac, Ana; Božić, Darko; Vučinac, Ivana; Vešligaj, Jasna; Vražić, Domagoj; Plancak, Darije

2013-09-01

The aim of this study was to investigate oral health behavior and attitudes of dental students in years 1 to 6 at the University of Zagreb, Croatia. The Croatian version of the Hiroshima University-Dental Behavioral Inventory (HU-DBI) was administered to predoctoral dental students, and collected data were analyzed. A total of 503 students (22.3 ± 2.6 mean age) completed the questionnaire. The response rate was 85.1 percent, and 72.4 percent of the respondents were female. These dental students' answers to eleven out of twenty HU-DBI items differed significantly by academic year. The mean questionnaire score was 6.62 ± 1.54, and the highest value of the HU-DBI score was in the fourth year (7.24 ± 1.54). First-year students were most likely to have a toothbrush with hard bristles and felt they had not brushed well unless done with hard strokes. Students in the sixth year were least worried about visiting a dentist and most frequently put off going to a dentist until having a toothache, indicating that rise of knowledge contributes to higher self-confidence. The mean HU-DBI score for these students showed average value, pointing out the need for a comprehensive oral hygiene and preventive program from the start of dental school.

Computer-aided diagnosis of lung cancer: definition and detection of ground-glass opacity type of nodules by high-resolution computed tomography.

PubMed

Okada, Tohru; Iwano, Shingo; Ishigaki, Takeo; Kitasaka, Takayuki; Hirano, Yasushi; Mori, Kensaku; Suenaga, Yasuhito; Naganawa, Shinji

2009-02-01

The ground-glass opacity (GGO) of lung cancer is identified only subjectively on computed tomography (CT) images as no quantitative characteristic has been defined for GGOs. We sought to define GGOs quantitatively and to differentiate between GGOs and solid-type lung cancers semiautomatically with a computer-aided diagnosis (CAD). High-resolution CT images of 100 pulmonary nodules (all peripheral lung cancers) were collected from our clinical records. Two radiologists traced the contours of nodules and distinguished GGOs from solid areas. The CT attenuation value of each area was measured. Differentiation between cancer types was assessed by a receiver-operating characteristic (ROC) analysis. The mean CT attenuation of the GGO areas was -618.4 +/- 212.2 HU, whereas that of solid areas was -68.1 +/- 230.3 HU. CAD differentiated between solidand GGO-type lung cancers with a sensitivity of 86.0% and specificity of 96.5% when the threshold value was -370 HU. Four nodules of mixed GGOs were incorrectly classified as the solid type. CAD detected 96.3% of GGO areas when the threshold between GGO and solid areas was 194 HU. Objective definition of GGO area by CT attenuation is feasible. This method is useful for semiautomatic differentiation between GGOs and solid types of lung cancer.

Effects of quantum noise in 4D-CT on deformable image registration and derived ventilation data

NASA Astrophysics Data System (ADS)

Latifi, Kujtim; Huang, Tzung-Chi; Feygelman, Vladimir; Budzevich, Mikalai M.; Moros, Eduardo G.; Dilling, Thomas J.; Stevens, Craig W.; van Elmpt, Wouter; Dekker, Andre; Zhang, Geoffrey G.

2013-11-01

Quantum noise is common in CT images and is a persistent problem in accurate ventilation imaging using 4D-CT and deformable image registration (DIR). This study focuses on the effects of noise in 4D-CT on DIR and thereby derived ventilation data. A total of six sets of 4D-CT data with landmarks delineated in different phases, called point-validated pixel-based breathing thorax models (POPI), were used in this study. The DIR algorithms, including diffeomorphic morphons (DM), diffeomorphic demons (DD), optical flow and B-spline, were used to register the inspiration phase to the expiration phase. The DIR deformation matrices (DIRDM) were used to map the landmarks. Target registration errors (TRE) were calculated as the distance errors between the delineated and the mapped landmarks. Noise of Gaussian distribution with different standard deviations (SD), from 0 to 200 Hounsfield Units (HU) in amplitude, was added to the POPI models to simulate different levels of quantum noise. Ventilation data were calculated using the ΔV algorithm which calculates the volume change geometrically based on the DIRDM. The ventilation images with different added noise levels were compared using Dice similarity coefficient (DSC). The root mean square (RMS) values of the landmark TRE over the six POPI models for the four DIR algorithms were stable when the noise level was low (SD <150 HU) and increased with added noise when the level is higher. The most accurate DIR was DD with a mean RMS of 1.5 ± 0.5 mm with no added noise and 1.8 ± 0.5 mm with noise (SD = 200 HU). The DSC values between the ventilation images with and without added noise decreased with the noise level, even when the noise level was relatively low. The DIR algorithm most robust with respect to noise was DM, with mean DSC = 0.89 ± 0.01 and 0.66 ± 0.02 for the top 50% ventilation volumes, as compared between 0 added noise and SD = 30 and 200 HU, respectively. Although the landmark TRE were stable with low noise, the differences between ventilation images increased with noise level, even when the noise was low, indicating ventilation imaging from 4D-CT was sensitive to image noise. Therefore, high quality 4D-CT is essential for accurate ventilation images.

Characterization of 3D printing techniques: Toward patient specific quality assurance spine-shaped phantom for stereotactic body radiation therapy.

PubMed

Kim, Min-Joo; Lee, Seu-Ran; Lee, Min-Young; Sohn, Jason W; Yun, Hyong Geon; Choi, Joon Yong; Jeon, Sang Won; Suh, Tae Suk

2017-01-01

Development and comparison of spine-shaped phantoms generated by two different 3D-printing technologies, digital light processing (DLP) and Polyjet has been purposed to utilize in patient-specific quality assurance (QA) of stereotactic body radiation treatment. The developed 3D-printed spine QA phantom consisted of an acrylic body phantom and a 3D-printed spine shaped object. DLP and Polyjet 3D printers using a high-density acrylic polymer were employed to produce spine-shaped phantoms based on CT images. Image fusion was performed to evaluate the reproducibility of our phantom, and the Hounsfield units (HUs) were measured based on each CT image. Two different intensity-modulated radiotherapy plans based on both CT phantom image sets from the two printed spine-shaped phantoms with acrylic body phantoms were designed to deliver 16 Gy dose to the planning target volume (PTV) and were compared for target coverage and normal organ-sparing. Image fusion demonstrated good reproducibility of the developed phantom. The HU values of the DLP- and Polyjet-printed spine vertebrae differed by 54.3 on average. The PTV Dmax dose for the DLP-generated phantom was about 1.488 Gy higher than that for the Polyjet-generated phantom. The organs at risk received a lower dose for the 3D printed spine-shaped phantom image using the DLP technique than for the phantom image using the Polyjet technique. Despite using the same material for printing the spine-shaped phantom, these phantoms generated by different 3D printing techniques, DLP and Polyjet, showed different HU values and these differently appearing HU values according to the printing technique could be an extra consideration for developing the 3D printed spine-shaped phantom depending on the patient's age and the density of the spinal bone. Therefore, the 3D printing technique and materials should be carefully chosen by taking into account the condition of the patient in order to accurately produce 3D printed patient-specific QA phantom.

Characterization of 3D printing techniques: Toward patient specific quality assurance spine-shaped phantom for stereotactic body radiation therapy

PubMed Central

Lee, Min-Young; Sohn, Jason W.; Yun, Hyong Geon; Choi, Joon Yong; Jeon, Sang Won

2017-01-01

Development and comparison of spine-shaped phantoms generated by two different 3D-printing technologies, digital light processing (DLP) and Polyjet has been purposed to utilize in patient-specific quality assurance (QA) of stereotactic body radiation treatment. The developed 3D-printed spine QA phantom consisted of an acrylic body phantom and a 3D-printed spine shaped object. DLP and Polyjet 3D printers using a high-density acrylic polymer were employed to produce spine-shaped phantoms based on CT images. Image fusion was performed to evaluate the reproducibility of our phantom, and the Hounsfield units (HUs) were measured based on each CT image. Two different intensity-modulated radiotherapy plans based on both CT phantom image sets from the two printed spine-shaped phantoms with acrylic body phantoms were designed to deliver 16 Gy dose to the planning target volume (PTV) and were compared for target coverage and normal organ-sparing. Image fusion demonstrated good reproducibility of the developed phantom. The HU values of the DLP- and Polyjet-printed spine vertebrae differed by 54.3 on average. The PTV Dmax dose for the DLP-generated phantom was about 1.488 Gy higher than that for the Polyjet-generated phantom. The organs at risk received a lower dose for the 3D printed spine-shaped phantom image using the DLP technique than for the phantom image using the Polyjet technique. Despite using the same material for printing the spine-shaped phantom, these phantoms generated by different 3D printing techniques, DLP and Polyjet, showed different HU values and these differently appearing HU values according to the printing technique could be an extra consideration for developing the 3D printed spine-shaped phantom depending on the patient’s age and the density of the spinal bone. Therefore, the 3D printing technique and materials should be carefully chosen by taking into account the condition of the patient in order to accurately produce 3D printed patient-specific QA phantom. PMID:28472175

SU-E-J-100: The Combination of Deformable Image Registration and Regions-Of-Interest Mapping Technique to Accomplish Accurate Dose Calculation On Cone Beam Computed Tomography for Esophageal Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Huang, B-T; Lu, J-Y

Purpose: We introduce a new method combined with the deformable image registration (DIR) and regions-of-interest mapping (ROIM) technique to accurately calculate dose on daily CBCT for esophageal cancer. Methods: Patients suffered from esophageal cancer were enrolled in the study. Prescription was set to 66 Gy/30 F and 54 Gy/30 F to the primary tumor (PTV66) and subclinical disease (PTV54) . Planning CT (pCT) were segmented into 8 substructures in terms of their differences in physical density, such as gross target volume (GTV), venae cava superior (SVC), aorta, heart, spinal cord, lung, muscle and bones. The pCT and its substructures weremore » transferred to the MIM software to readout their mean HU values. Afterwards, a deformable planning CT to daily KV-CBCT image registration method was then utilized to acquire a new structure set on CBCT. The newly generated structures on CBCT were then transferred back to the treatment planning system (TPS) and its HU information were overridden manually with mean HU values obtained from pCT. Finally, the treatment plan was projected onto the CBCT images with the same beam arrangements and monitor units (MUs) to accomplish dose calculation. Planning target volume (PTV) and organs at risk (OARs) from both of the pCT and CBCT were compared to evaluate the dose calculation accuracy. Results: It was found that the dose distribution in the CBCT showed little differences compared to the pCT, regardless of whether PTV or OARs were concerned. Specifically, dose variation in GTV, PTV54, PTV66, SVC, lung and heart were within 0.1%. The maximum dose variation was presented in the spinal cord, which was up to 2.7% dose difference. Conclusion: The proposed method combined with DIR and ROIM technique to accurately calculate dose distribution on CBCT for esophageal cancer is feasible.« less

Quantification of epicardial adipose tissue in coronary calcium score and CT coronary angiography image data sets: comparison of attenuation values, thickness and volumes.

PubMed

La Grutta, Ludovico; Toia, Patrizia; Farruggia, Alfonso; Albano, Domenico; Grassedonio, Emanuele; Palmeri, Antonella; Maffei, Erica; Galia, Massimo; Vitabile, Salvatore; Cademartiri, Filippo; Midiri, Massimo

2016-06-01

The aim of the study was to compare epicardial adipose tissue (EAT) characteristics assessed with coronary calcium score (CS) and CT coronary angiography (CTCA) image data sets. In 76 patients (mean age 59 ± 13 years) who underwent CS and CTCA owing to suspected coronary artery disease (CAD), EAT was quantified in terms of density (Hounsfield units), thickness and volume. The EAT volume was extracted with a semi-automatic software. A moderate correlation was found between EAT density in CS and CTCA image data sets (-100 ± 19 HU vs -70 ± 24 HU; p < 0.05, r = 0.55). The distribution of EAT was not symmetrical with a maximal thickness at the right atrioventricular groove (14.2 ± 5.3 mm in CS, 15.7 ± 5 mm in CTCA; p > 0.05, r = 0.76). The EAT volume resulted as 122 ± 50 cm(3) in CS and 86 ± 40 cm(3) in CTCA (Δ = 30%, p < 0.05, r = 0.92). After adjustment for post-contrast EAT attenuation difference (Δ = 30 HU), the volume was 101 ± 47 cm(3) (Δ = 17%, p < 0.05, r = 0.92). Based on EAT volume median values, no differences were found between groups with smaller and larger volumes in terms of Agatston score and CAD severity. CS and CTCA image data sets may be equally employed for EAT assessment; however, an underestimation of volume is found with the latter acquisition even after post-contrast attenuation adjustment. EAT may be measured by processing either the CS or CTCA image data sets.

Human plasma kallikrein and tissue kallikrein binding to a substrate based on the reactive site of a factor Xa inhibitor isolated from Bauhinia ungulata seeds.

PubMed

Oliva, M L; Andrade, S A; Batista, I F; Sampaio, M U; Juliano, M; Fritz, H; Auerswald, E A; Sampaio, C A

1999-12-01

Kunitz type Bauhinia ungulata factor Xa inhibitor (BuXI) was purified from B. ungulata seeds. BuXI inactivates factor Xa and human plasma kallikrein (HuPK) with Ki values of 18.4 and 6.9 nM, respectively. However, Bauhinia variegata trypsin inhibitor (BvTI) which is 70% homologous to BuXI does not inhibit factor Xa and is less efficient on HuPK (Ki = 80 nM). The comparison between BuXI and BvTI reactive site structure indicates differences at Met59, Thr66 and Met67 residues. The hydrolysis rate of quenched fluorescence peptide substrates based on BuXI reactive site sequence, Abz-VMIAALPRTMFIQ-EDDnp (leading peptide), by HuPK and porcine pancreatic kallikrein (PoPK) is low, but hydrolysis is enhanced with Abz-VMIAALPRTMQ-EDDnp, derived from the leading peptide shortened by removing the dipeptide Phe-Ileu from the C-terminal portion, for HuPK (Km = 0.68 microM, k(cat)/Km = 1.3 x 10(6) M(-1) s(-1)), and the shorter substrate Abz-LPRTMQ-EDDnp is better for PoPK (Km = 0.66 microM, k(cat)/Km = 2.2 x 10(3) M(-1) s(-1)). The contribution of substrate methionine residues to HuPK and PoPK hydrolysis differs from that observed with factor Xa. The determined Km and k(cat) values suggest that the substrates interact with kallikreins the same as an enzyme and inhibitor interacts to form complexes.

Exploration of the metal coordination region of concanavalin A for its interaction with human norovirus.

PubMed

Kim, Duwoon; Lee, Hee-Min; Oh, Kyung-Seo; Ki, Ah Young; Protzman, Rachael A; Kim, Dongkyun; Choi, Jong-Soon; Kim, Min Ji; Kim, Sung Hyun; Vaidya, Bipin; Lee, Seung Jae; Kwon, Joseph

2017-06-01

Rapid methods for the detection and clinical treatment of human norovirus (HuNoV) are needed to control foodborne disease outbreaks, but reliable techniques that are fast and sensitive enough to detect small amounts of HuNoV in food and aquatic environments are not yet available. We explore the interactions between HuNoV and concanavalin A (Con A), which could facilitate the development of a sensitive detection tool for HuNoV. Biophysical studies including hydrogen/deuterium exchange (HDX) mass spectrometry and surface plasmon resonance (SPR) revealed that when the metal coordinated region of Con A, which spans Asp16 to His24, is converted to nine alanine residues (mCon A MCR ), the affinity for HuNoV (GII.4) diminishes, demonstrating that this Ca 2+ and Mn 2+ coordinated region is responsible for the observed virus-protein interaction. The mutated carbohydrate binding region of Con A (mCon A CBR ) does not affect binding affinity significantly, indicating that MCR of Con A is a major region of interaction to HuNoV (GII.4). The results further contribute to the development of a HuNoV concentration tool, Con A-immobilized polyacrylate beads (Con A-PAB), for rapid detection of genotypes from genogroups I and II (GI and GII). This method offers many advantages over currently available methods, including a short concentration time. HuNov (GI and GII) can be detected in just 15 min with 90% recovery through Con A-PAB application. In addition, this method can be used over a wide range of pH values (pH 3.0 - 10.0). Overall, this rapid and sensitive detection of HuNoV (GI and GII) will aid in the prevention of virus transmission pathways, and the method developed here may have applicability for other foodborne viral infections. Copyright © 2017 Elsevier Ltd. All rights reserved.

Stability of and Attachment to Lettuce by a Culturable Porcine Sapovirus Surrogate for Human Caliciviruses

PubMed Central

Zhang, Zhenwen

2012-01-01

Human noroviruses (HuNoVs) are the leading cause of food-borne illness, accounting for 58% of U.S. cases. Because HuNoVs are unculturable, surrogates are needed to investigate transmission routes and evaluate disinfection methods. However, the current surrogates, feline calicivirus (FCV) and murine NoV (MNV), are less tolerant than HuNoVs to acid and chlorine, respectively. Porcine sapovirus (SaV) is the only culturable enteropathogenic calicivirus. In this study, the resistance of SaV to physicochemical treatments was compared to that of HuNoVs (by reverse transcription-PCR), FCV, and MNV (by infectivity assays). Sapovirus and HuNoV (viral RNA) showed similar resistances to heat (56°C) and to different concentrations of chlorine. However, SaV was more resistant than HuNoVs to ethanol treatment (60% and 70%). Like HuNoVs, SaV was stable at pH 3.0 to 8.0, with a <1.0 log10 50% tissue culture infective dose (TCID50) reduction at pH 3.0 compared to the value for pH 4.0 to 8.0. SaV and MNV showed similar resistances, and both were more resistant than FCV to heat inactivation (56°C). FCV was more resistant than MNV and SaV to ethanol, and all three viruses showed similar resistances to treatment with low concentrations of chlorine for 1 min. Those results indicate that SaV is a promising surrogate for HuNoVs. Next, we used SaV as a surrogate to examine virus attachment to lettuce at different pHs. Sapovirus attached to lettuce leaves significantly at its capsid isoelectric point (pH 5.0), and the attached viral particles remained infectious on lettuce after 1 week of storage at 4°C. The culturable SaV is a good surrogate for studying HuNoV contamination and transmission in leafy greens and potential disinfectants. PMID:22447610

SU-F-R-50: Radiation-Induced Changes in CT Number Histogram During Chemoradiation Therapy for Pancreatic Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, X; Schott, D; Song, Y

Purpose: In an effort of early assessment of treatment response, we investigate radiation induced changes in CT number histogram of GTV during the delivery of chemoradiation therapy (CRT) for pancreatic cancer. Methods: Diagnostic-quality CT data acquired daily during routine CT-guided CRT using a CT-on-rails for 20 pancreatic head cancer patients were analyzed. All patients were treated with a radiation dose of 50.4 in 28 fractions. On each daily CT set, the contours of the pancreatic head and the spinal cord were delineated. The Hounsfiled Units (HU) histogram in these contourswere extracted and processed using MATLAB. Eight parameters of the histogrammore » including the mean HU over all the voxels, peak position, volume, standard deviation (SD), skewness, kurtosis, energy, and entropy were calculated for each fraction. The significances were inspected using paired two-tailed t-test and the correlations were analyzed using Spearman rank correlation tests. Results: In general, HU histogram in pancreatic head (but not in spinal cord) changed during the CRT delivery. Changes from the first to the last fraction in mean HU in pancreatic head ranged from −13.4 to 3.7 HU with an average of −4.4 HU, which was significant (P<0.001). Among other quantities, the volume decreased, the skewness increased (less skewed), and the kurtosis decreased (less sharp) during the CRT delivery. The changes of mean HU, volume, skewness, and kurtosis became significant after two weeks of treatment. Patient pathological response status is associated with the changes of SD (ΔSD), i.e., ΔSD= 1.85 (average of 7 patients) for good reponse, −0.08 (average of 6 patients) for moderate and poor response. Conclusion: Significant changes in HU histogram and the histogram-based metrics (e.g., meam HU, skewness, and kurtosis) in tumor were observed during the course of chemoradiation therapy for pancreas cancer. These changes may be potentially used for early assessment of treatment response.« less

TH-CD-202-02: A Preliminary Study Evaluating Beam-Hardening Artifact Reduction On CT Direct Electron-Density Images

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, H; Dolly, S; Zhao, T

Purpose: A prototype reconstruction algorithm that can provide direct electron density (ED) images from single energy CT scans is being currently developed by Siemens Healthcare GmbH. This feature can eliminate the need for kV specific calibration curve for radiation treatemnt planning. An added benefit is that beam-hardening artifacts are also reduced on direct-ED images due to the underlying material decomposition. This study is to quantitatively analyze the reduction of beam-hardening artifacts on direct-ED images and suggest additional clinical usages. Methods: HU and direct-ED images were reconstructed on a head phantom scanned on a Siemens Definition AS CT scanner at fivemore » tube potentials of 70kV, 80kV, 100kV, 120kV and 140kV respectively. From these images, mean, standard deviation (SD), and local NPS were calculated for regions of interest (ROI) of same locations and sizes. A complete analysis of beam-hardening artifact reduction and image quality improvement was conducted. Results: Along with the increase of tube potentials, ROI means and SDs decrease on both HU and direct-ED images. The mean value differences between HU and direct-ED images are up to 8% with absolute value of 2.9. Compared to that on HU images, the SDs are lower on direct-ED images, and the differences are up to 26%. Interestingly, the local NPS calculated from direct-ED images shows consistent values in the low spatial frequency domain for images acquired from all tube potential settings, while varied dramatically on HU images. This also confirms the beam -hardening artifact reduction on ED images. Conclusions: The low SDs on direct-ED images and relative consistent NPS values in the low spatial frequency domain indicate a reduction of beam-hardening artifacts. The direct-ED image has the potential to assist in more accurate organ contouring, and is a better fit for the desired purpose of CT simulations for radiotherapy.« less

TH-CD-207B-10: Effect of CT Reconstruction Filter On Measured Hounsfield Values in Lung Nodules

DOE Office of Scientific and Technical Information (OSTI.GOV)

Little, K; Reiser, I; Sanchez, A

Purpose: Measured Hounsfield numbers in CT are used by radiologists to determine the presence of calcium or fat in lung nodules, either of which suggests a benign diagnosis. However, substantial variations in Hounsfield number may arise due to the use of different reconstruction parameters such as the filter/kernel, leading to measurement inaccuracies. This quality improvement project was developed to demonstrate measurement pitfalls and to identify acceptable conditions for incorporating Hounsfield values as a factor in lung nodule diagnosis. Methods: 12 mm-diameter spheres of polyurethane and urethane foam were placed into an anthropomorphic chest phantom, and 10 mm-diameter tubes with varyingmore » iodine concentrations were placed into a 16 cm PMMA cylindrical phantom. Additionally, 11 mm-diameter PMMA and HDPE spheres were placed in a 10 cm PMMA cylindrical phantom. Phantoms were scanned at 120 kVp using a Siemens Biograph mCT and on a Philips iCT and reconstructed using various reconstruction filters. Results: For the Siemens system, both sharp kernels and smooth kernels altered the Hounsfield numbers. Hounsfield numbers varied within a range of 8.9 HU for urethane foam and varied within 58.7 HU for polyurethane. The iodine measurements varied up to 37.9 HU for the lowest concentration. For the Philips system, Hounsfield numbers were relatively consistent but were higher for the “Detail” and “Lung Enhanced” filters, varying by 36.9 HU for PMMA and 15.9 HU for HDPE. Conclusion: Reconstruction filters can change the measured Hounsfield numbers of nodular objects, especially with detail-enhancing (sharpening) filters commonly used in lung imaging. Measured values should only be used for diagnostic decision support with filters that have demonstrated accuracy and consistency. While filter accuracy statements are available from manufacturers, radiologists are likely not aware of the extent of potential variations that can occur in a clinical setting.« less

Establishment of the first humpback whale fibroblast cell lines and their application in chemical risk assessment.

PubMed

Burkard, Michael; Whitworth, Deanne; Schirmer, Kristin; Nash, Susan Bengtson

2015-10-01

This paper reports the first successful derivation and characterization of humpback whale fibroblast cell lines. Primary fibroblasts were isolated from the dermal connective tissue of skin biopsies, cultured at 37 °C and 5% CO2 in the standard mammalian medium DMEM/F12 supplemented with 10% fetal bovine serum (FBS). Of nine initial biopsies, two cell lines were established from two different animals and designated HuWa1 and HuWa2. The cells have a stable karyotype with 2n=44, which has commonly been observed in other baleen whale species. Cells were verified as being fibroblasts based on their spindle-shaped morphology, adherence to plastic and positive immunoreaction to vimentin. Population doubling time was determined to be ∼41 h and cells were successfully cryopreserved and thawed. To date, HuWa1 cells have been propagated 30 times. Cells proliferate at the tested temperatures, 30, 33.5 and 37 °C, but show the highest rate of proliferation at 37 °C. Short-term exposure to para,para'-dichlorodiphenyldichloroethylene (p,p'-DDE), a priority compound accumulating in southern hemisphere humpback whales, resulted in a concentration-dependent loss of cell viability. The effective concentration which caused a 50% reduction in HuWa1 cell viability (EC50 value) was approximately six times greater than the EC50 value for the same chemical measured with human dermal fibroblasts. HuWa1 exposed to a natural, p,p'-DDE-containing, chemical mixture extracted from whale blubber showed distinctively higher sensitivity than to p,p'-DDE alone. Thus, we provide the first cytotoxicological data for humpback whales and with establishment of the HuWa cell lines, a unique in vitro model for the study of the whales' sensitivity and cellular response to chemicals and other environmental stressors. Copyright © 2015 Elsevier B.V. All rights reserved.

Standardizing CT lung density measure across scanner manufacturers.

PubMed

Chen-Mayer, Huaiyu Heather; Fuld, Matthew K; Hoppel, Bernice; Judy, Philip F; Sieren, Jered P; Guo, Junfeng; Lynch, David A; Possolo, Antonio; Fain, Sean B

2017-03-01

Computed Tomography (CT) imaging of the lung, reported in Hounsfield Units (HU), can be parameterized as a quantitative image biomarker for the diagnosis and monitoring of lung density changes due to emphysema, a type of chronic obstructive pulmonary disease (COPD). CT lung density metrics are global measurements based on lung CT number histograms, and are typically a quantity specifying either the percentage of voxels with CT numbers below a threshold, or a single CT number below which a fixed relative lung volume, nth percentile, falls. To reduce variability in the density metrics specified by CT attenuation, the Quantitative Imaging Biomarkers Alliance (QIBA) Lung Density Committee has organized efforts to conduct phantom studies in a variety of scanner models to establish a baseline for assessing the variations in patient studies that can be attributed to scanner calibration and measurement uncertainty. Data were obtained from a phantom study on CT scanners from four manufacturers with several protocols at various tube potential voltage (kVp) and exposure settings. Free from biological variation, these phantom studies provide an assessment of the accuracy and precision of the density metrics across platforms solely due to machine calibration and uncertainty of the reference materials. The phantom used in this study has three foam density references in the lung density region, which, after calibration against a suite of Standard Reference Materials (SRM) foams with certified physical density, establishes a HU-electron density relationship for each machine-protocol. We devised a 5-step calibration procedure combined with a simplified physical model that enabled the standardization of the CT numbers reported across a total of 22 scanner-protocol settings to a single energy (chosen at 80 keV). A standard deviation was calculated for overall CT numbers for each density, as well as by scanner and other variables, as a measure of the variability, before and after the standardization. In addition, a linear mixed-effects model was used to assess the heterogeneity across scanners, and the 95% confidence interval of the mean CT number was evaluated before and after the standardization. We show that after applying the standardization procedures to the phantom data, the instrumental reproducibility of the CT density measurement of the reference foams improved by more than 65%, as measured by the standard deviation of the overall mean CT number. Using the lung foam that did not participate in the calibration as a test case, a mixed effects model analysis shows that the 95% confidence intervals are [-862.0 HU, -851.3 HU] before standardization, and [-859.0 HU, -853.7 HU] after standardization to 80 keV. This is in general agreement with the expected CT number value at 80 keV of -855.9 HU with 95% CI of [-857.4 HU, -854.5 HU] based on the calibration and the uncertainty in the SRM certified density. This study provides a quantitative assessment of the variations expected in CT lung density measures attributed to non-biological sources such as scanner calibration and scanner x-ray spectrum and filtration. By removing scanner-protocol dependence from the measured CT numbers, higher accuracy and reproducibility of quantitative CT measures were attainable. The standardization procedures developed in study may be explored for possible application in CT lung density clinical data. © 2017 American Association of Physicists in Medicine.

A mild transient decrease of peripheral red blood cell counts induced by a suprapharmacological dose of pegylated human megakaryocyte growth and development factor in rats.

PubMed

Harada, K; Ide, Y; Tazunoki, Y; Imai, A; Yanagida, M; Kikuchi, Y; Imai, A; Ishii, H; Kawahara, J; Izumi, H; Kusaka, M; Tokiwa, T

1999-07-01

Previous studies have shown that pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF) at suprapharmacological dose induces a mild transient decrease of red blood cell counts according to thrombopoiesis in normal mice. To unravel the mechanism underlying this mild transient decrease of red blood cells, we have studied the effect of PEG-rHuMGDF on the circulating plasma and blood volume, and the serum biochemical parameters of anaemia and splenectomy. Also, we have performed histological studies of the bone marrow and the spleen of PEG-rHuMGDF-treated rats. PEG-rHuMGDF (300 microg kg(-1)]) or vehicle was subcutaneously administered to rats once a day for up to five days. From day 6 after the start of PEG-rHuMGDF administration, the platelet counts and plateletcrit levels were significantly increased, reaching peak values on day 10, and recovering to normal by day 20. The red blood cell counts and the haematocrit levels were significantly decreased on day 6 to 13. The decreases in red blood cell levels and haematocrit produced by PEG-rHuMGDF treatment were mild and had recovered by day 15. The plasma and blood volumes were significantly increased on day 10 in PEG-rHuMGDF-treated rats. No alteration of the serum biochemical parameters for anaemia, iron or total bilirubin, were observed on day 10. The histological examination on day 10 revealed a marked increase in megakaryocytes and a slight decrease in erythropoiesis in the bone marrow of rats that received PEG-rHuMGDF (300 microg kg(-1)). There was also a slight increase in splenic megakaryocytes and erythropoiesis. The decrease of red blood cells by PEG-rHuMGDF was not affected by splenectomy. These results suggest that the mild transient decrease of red blood cells induced by PEG-rHuMGDF treatment for up to five days is based mainly on the increases in the plasma and blood volume. These events are secondary changes due to the regulation of the excess production of megakaryocytes in the marrow and the peripheral platelets.

Computed tomographic evaluation of abdominal fat in minipigs.

PubMed

Chang, Jinhwa; Jung, Joohyun; Lee, Hyeyeon; Chang, Dongwoo; Yoon, Junghee; Choi, Mincheol

2011-03-01

Computed tomography (CT) exams were conducted to determine the distribution of abdominal fat identified based on the CT number measured in Hounsfield Units (HU) and to measure the volume of the abdominal visceral and subcutaneous fat in minipigs. The relationship between the CT-based fat volumes of several vertebral levels and the entire abdomen and anthropometric data including the sagittal abdominal diameter and waist circumference were evaluated. Moreover, the total fat volumes at the T11, T13, L3, and L5 levels were compared with the total fat volume of the entire abdomen to define the landmark of abdominal fat distribution. Using a single-detector CT, six 6-month-old male minipigs were scanned under general anesthesia. Three radiologists then assessed the HU value of visceral and subcutaneous abdominal fat by drawing the region of interest manually at the T11, T13, L1, L3, and L5 levels. The CT number and abdominal fat determined in this way by the three radiologists was found to be correlated (intra-class coefficient = 0.9). The overall HU ranges for the visceral and subcutaneous fat depots were -147.47 to -83.46 and -131.62 to -90.97, respectively. The total fat volume of the entire abdomen was highly correlated with the volume of abdominal fat at the T13 level (r = 0.97, p < 0.0001). These findings demonstrate that the volume of abdominal adipose tissue measured at the T13 level using CT is a strong and reliable predictor of total abdominal adipose volume.

Magnetic Resonance–Based Automatic Air Segmentation for Generation of Synthetic Computed Tomography Scans in the Head Region

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zheng, Weili; Kim, Joshua P.; Kadbi, Mo

2015-11-01

Purpose: To incorporate a novel imaging sequence for robust air and tissue segmentation using ultrashort echo time (UTE) phase images and to implement an innovative synthetic CT (synCT) solution as a first step toward MR-only radiation therapy treatment planning for brain cancer. Methods and Materials: Ten brain cancer patients were scanned with a UTE/Dixon sequence and other clinical sequences on a 1.0 T open magnet with simulation capabilities. Bone-enhanced images were generated from a weighted combination of water/fat maps derived from Dixon images and inverted UTE images. Automated air segmentation was performed using unwrapped UTE phase maps. Segmentation accuracy was assessedmore » by calculating segmentation errors (true-positive rate, false-positive rate, and Dice similarity indices using CT simulation (CT-SIM) as ground truth. The synCTs were generated using a voxel-based, weighted summation method incorporating T2, fluid attenuated inversion recovery (FLAIR), UTE1, and bone-enhanced images. Mean absolute error (MAE) characterized Hounsfield unit (HU) differences between synCT and CT-SIM. A dosimetry study was conducted, and differences were quantified using γ-analysis and dose-volume histogram analysis. Results: On average, true-positive rate and false-positive rate for the CT and MR-derived air masks were 80.8% ± 5.5% and 25.7% ± 6.9%, respectively. Dice similarity indices values were 0.78 ± 0.04 (range, 0.70-0.83). Full field of view MAE between synCT and CT-SIM was 147.5 ± 8.3 HU (range, 138.3-166.2 HU), with the largest errors occurring at bone–air interfaces (MAE 422.5 ± 33.4 HU for bone and 294.53 ± 90.56 HU for air). Gamma analysis revealed pass rates of 99.4% ± 0.04%, with acceptable treatment plan quality for the cohort. Conclusions: A hybrid MRI phase/magnitude UTE image processing technique was introduced that significantly improved bone and air contrast in MRI. Segmented air masks and bone-enhanced images were integrated into our synCT pipeline for brain, and results agreed well with clinical CTs, thereby supporting MR-only radiation therapy treatment planning in the brain.« less

Magnetic Resonance-Based Automatic Air Segmentation for Generation of Synthetic Computed Tomography Scans in the Head Region.

PubMed

Zheng, Weili; Kim, Joshua P; Kadbi, Mo; Movsas, Benjamin; Chetty, Indrin J; Glide-Hurst, Carri K

2015-11-01

To incorporate a novel imaging sequence for robust air and tissue segmentation using ultrashort echo time (UTE) phase images and to implement an innovative synthetic CT (synCT) solution as a first step toward MR-only radiation therapy treatment planning for brain cancer. Ten brain cancer patients were scanned with a UTE/Dixon sequence and other clinical sequences on a 1.0 T open magnet with simulation capabilities. Bone-enhanced images were generated from a weighted combination of water/fat maps derived from Dixon images and inverted UTE images. Automated air segmentation was performed using unwrapped UTE phase maps. Segmentation accuracy was assessed by calculating segmentation errors (true-positive rate, false-positive rate, and Dice similarity indices using CT simulation (CT-SIM) as ground truth. The synCTs were generated using a voxel-based, weighted summation method incorporating T2, fluid attenuated inversion recovery (FLAIR), UTE1, and bone-enhanced images. Mean absolute error (MAE) characterized Hounsfield unit (HU) differences between synCT and CT-SIM. A dosimetry study was conducted, and differences were quantified using γ-analysis and dose-volume histogram analysis. On average, true-positive rate and false-positive rate for the CT and MR-derived air masks were 80.8% ± 5.5% and 25.7% ± 6.9%, respectively. Dice similarity indices values were 0.78 ± 0.04 (range, 0.70-0.83). Full field of view MAE between synCT and CT-SIM was 147.5 ± 8.3 HU (range, 138.3-166.2 HU), with the largest errors occurring at bone-air interfaces (MAE 422.5 ± 33.4 HU for bone and 294.53 ± 90.56 HU for air). Gamma analysis revealed pass rates of 99.4% ± 0.04%, with acceptable treatment plan quality for the cohort. A hybrid MRI phase/magnitude UTE image processing technique was introduced that significantly improved bone and air contrast in MRI. Segmented air masks and bone-enhanced images were integrated into our synCT pipeline for brain, and results agreed well with clinical CTs, thereby supporting MR-only radiation therapy treatment planning in the brain. Copyright © 2015 Elsevier Inc. All rights reserved.

Patient size and x-ray transmission in body CT.

PubMed

Ogden, Kent; Huda, Walter; Scalzetti, Ernest M; Roskopf, Marsha L

2004-04-01

Physical characteristics were obtained for 196 patients undergoing chest and abdomen computed tomography (CT) examinations. Computed tomography sections for these patients having no evident pathology were analyzed to determine patient dimensions (AP and lateral), together with the average attenuation coefficient. Patient weights ranged from approximately 3 kg to about 120 kg. For chest CT, the mean Hounsfield unit (HU) fell from about -120 HU for newborns to about -300 HU for adults. For abdominal CT, the mean HU for children and normal-sized adults was about 20 HU, but decreased to below -50 HU for adults weighing more than 100 kg. The effective photon energy and percent energy fluence transmitted through a given patient size and composition was calculated for representative x-ray spectra at 80, 100, 120, and 140 kV tube potentials. A 70-kg adult scanned at 120 kVp transmits 2.6% of the energy fluence for chest and 0.7% for abdomen CT examinations. Reducing the patient size to 10 kg increases transmission by an order of magnitude. For 70 kg patients, effective energies in body CT range from approximately 50 keV at 80 kVp to approximately 67 keV at 140 kVp; increasing patient size from 10 to 120 kg resulted in an increase in effective photon energy of approximately 4 keV. The x-ray transmission data and effective photon energy data can be used to determine CT image noise and image contrast, respectively, and information on patient size and composition can be used to determine patient doses.

Improved scatter correction using adaptive scatter kernel superposition

NASA Astrophysics Data System (ADS)

Sun, M.; Star-Lack, J. M.

2010-11-01

Accurate scatter correction is required to produce high-quality reconstructions of x-ray cone-beam computed tomography (CBCT) scans. This paper describes new scatter kernel superposition (SKS) algorithms for deconvolving scatter from projection data. The algorithms are designed to improve upon the conventional approach whose accuracy is limited by the use of symmetric kernels that characterize the scatter properties of uniform slabs. To model scatter transport in more realistic objects, nonstationary kernels, whose shapes adapt to local thickness variations in the projection data, are proposed. Two methods are introduced: (1) adaptive scatter kernel superposition (ASKS) requiring spatial domain convolutions and (2) fast adaptive scatter kernel superposition (fASKS) where, through a linearity approximation, convolution is efficiently performed in Fourier space. The conventional SKS algorithm, ASKS, and fASKS, were tested with Monte Carlo simulations and with phantom data acquired on a table-top CBCT system matching the Varian On-Board Imager (OBI). All three models accounted for scatter point-spread broadening due to object thickening, object edge effects, detector scatter properties and an anti-scatter grid. Hounsfield unit (HU) errors in reconstructions of a large pelvis phantom with a measured maximum scatter-to-primary ratio over 200% were reduced from -90 ± 58 HU (mean ± standard deviation) with no scatter correction to 53 ± 82 HU with SKS, to 19 ± 25 HU with fASKS and to 13 ± 21 HU with ASKS. HU accuracies and measured contrast were similarly improved in reconstructions of a body-sized elliptical Catphan phantom. The results show that the adaptive SKS methods offer significant advantages over the conventional scatter deconvolution technique.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, J; Li, X; Liu, G

Purpose: We compare and investigate the dosimetric impacts on pencil beam scanning (PBS) proton treatment plans generated with CT calibration curves from four different CT scanners and one averaged ‘global’ CT calibration curve. Methods: The four CT scanners are located at three different hospital locations within the same health system. CT density calibration curves were collected from these scanners using the same CT calibration phantom and acquisition parameters. Mass density to HU value tables were then commissioned in a commercial treatment planning system. Five disease sites were chosen for dosimetric comparisons at brain, lung, head and neck, adrenal, and prostate.more » Three types of PBS plans were generated at each treatment site using SFUD, IMPT, and robustness optimized IMPT techniques. 3D dose differences were investigated using 3D Gamma analysis. Results: The CT calibration curves for all four scanners display very similar shapes. Large HU differences were observed at both the high HU and low HU regions of the curves. Large dose differences were generally observed at the distal edges of the beams and they are beam angle dependent. Out of the five treatment sites, lung plans exhibits the most overall range uncertainties and prostate plans have the greatest dose discrepancy. There are no significant differences between the SFUD, IMPT, and the RO-IMPT methods. 3D gamma analysis with 3%, 3 mm criteria showed all plans with greater than 95% passing rate. Two of the scanners with close HU values have negligible dose difference except for lung. Conclusion: Our study shows that there are more than 5% dosimetric differences between different CT calibration curves. PBS treatment plans generated with SFUD, IMPT, and the robustness optimized IMPT has similar sensitivity to the CT density uncertainty. More patient data and tighter gamma criteria based on structure location and size will be used for further investigation.« less

Stone heterogeneity index on single-energy noncontrast computed tomography can be a positive predictor of urinary stone composition

PubMed Central

Lee, Jong Soo; Cho, Kang Su; Lee, Seung Hwan; Yoon, Young Eun; Kang, Dong Hyuk; Jeong, Won Sik; Jung, Hae Do; Kwon, Jong Kyou

2018-01-01

The aim of this study was to investigate the correlation between stone composition and single-energy noncontrast computed tomography (NCCT) parameters, including stone heterogeneity index (SHI) and mean stone density (MSD), in patients with urinary calculi. We retrospectively reviewed medical records of 255 patients who underwent operations or procedures for urinary stones or had spontaneous stone passage between December 2014 and October 2015. Among these, 214 patients with urinary calculi who underwent NCCT and stone composition analyses were included in the study. Maximal stone length (MSL), mean stone density (MSD), and stone heterogeneity index (SHI) were determined on pretreatment NCCT. The mean MSD (454.68±177.80 HU) and SHI (115.82±96.31 HU) of uric acid stones were lower than those of all other types. Based on post hoc tests, MSD was lower for uric acid stones than for the other types (vs. CaOx: P<0.001; vs. infection stones: P<0.001). SHI was lower for uric acid stones than for the other types (vs. CaOx: P<0.001; vs. infection stones: P<0.001) Receiver operating characteristic curves of uric acid stones for MSD and SHI demonstrated that SHI (cut-off value: 140.4 HU) was superior to MSD (cut-off value: 572.3 HU) in predicting uric acid stones (P<0.001). PMID:29649219

Effect of Hindlimb Unweighting on Tissue Blood Flow in the Rat

NASA Technical Reports Server (NTRS)

McDonald, K. S.; Delp, M. D.; Fitts, R. H.

1992-01-01

The purpose of this study was to characterize the distribution of blood flow in the rat during hindlimb unweighting (HU) and post-HU standing and exercise and examine whether the previously reported elevation in anaerobic metabolism observed with contractile activity in the atrophied soleus muscle was caused by a reduced hindlimb blood flow. After either 15 days of HU or cage control, blood flow was measured with radioactive microspheres during unweighting, normal standing, and running on a treadmill (15 m/min). In another group of control and experimental animals, blood flow was measured during preexercise (PE) treadmill standing and treadmill running (15 m/min). Soleus muscle blood flow was not different between groups during unweighting, PE standing, and running at 15 m/min. Chronic unweighting resulted in the tendency for greater blood flow to muscles composed of predominantly fast-twitch glycolytic fibers. With exercise, blood flow to visceral organs was reduced compared with PE values in the control rats, whereas flow to visceral organs in 15-day HU animals was unaltered by exercise. These higher flows to the viscera and to muscles composed of predominantly fast-twitch glycolytic fibers suggest an apparent reduction in the ability of the sympathetic nervous system to distribute cardiac output after chronic HU. In conclusion, because 15 days of HU did not affect blood flow to the soleus during exercise, the increased dependence of the atrophied soleus on anerobic energy production during contractile activity cannot be explained by a reduced muscle blood flow.

TH-CD-202-01: BEST IN PHYSICS (JOINT IMAGING-THERAPY): Evaluation of the Use of Direct Electron Density CT Images in Radiation Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhao, T; Sun, B; Li, H

Purpose: The current standard for calculation of photon and electron dose requires conversion of Hounsfield Units (HU) to Electron Density (ED) by applying a calibration curve specifically constructed for the corresponding CT tube voltage. This practice limits the use of the CT scanner to a single tube voltage and hinders the freedom in the selection of optimal tube voltage for better image quality. The objective of this study is to report a prototype CT reconstruction algorithm that provides direct ED images from the raw CT data independently of tube voltages used during acquisition. Methods: A tissue substitute phantom was scannedmore » for Stoichiometric CT calibrations at tube voltages of 70kV, 80kV, 100kV, 120kV and 140kV respectively. HU images and direct ED images were acquired sequentially on a thoracic anthropomorphic phantom at the same tube voltages. Electron densities converted from the HU images were compared to ED obtained from the direct ED images. A 7-field treatment plan was made on all HU and ED images. Gamma analysis was performed to demonstrate quantitatively dosimetric change from the two schemes in acquiring ED. Results: The average deviation of EDs obtained from the direct ED images was −1.5%±2.1% from the EDs from HU images with the corresponding CT calibration curves applied. Gamma analysis on dose calculated on the direct ED images and the HU images acquired at the same tube voltage indicated negligible difference with lowest passing rate at 99.9%. Conclusion: Direct ED images require no CT calibration while demonstrate equivalent dosimetry compared to that obtained from standard HU images. The ability of acquiring direct ED images simplifies the current practice at a safer level by eliminating CT calibration and HU conversion from commissioning and treatment planning respectively. Furthermore, it unlocks a wider range of tube voltages in CT scanner for better imaging quality while maintaining similar dosimetric accuracy.« less

West Foster Creek 2007 Follow-up Habitat Evaluation Procedures (HEP) Report.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ashley, Paul R.

A follow-up habitat evaluation procedures (HEP) analysis was conducted on the West Foster Creek (Smith acquisition) wildlife mitigation site in May 2007 to determine the number of additional habitat units to credit Bonneville Power Administration (BPA) for providing funds to enhance and maintain the project site as partial mitigation for habitat losses associated with construction of Grand Coulee Dam. The West Foster Creek 2007 follow-up HEP survey generated 2,981.96 habitat units (HU) or 1.51 HUs per acre for a 34% increase (+751.34 HUs) above baseline HU credit (the 1999 baseline HEP survey generated 2,230.62 habitat units or 1.13 HUs permore » acre). The 2007 follow-up HEP analysis yielded 1,380.26 sharp-tailed grouse (Tympanuchus phasianellus) habitat units, 879.40 mule deer (Odocoileus hemionus) HUs, and 722.29 western meadowlark (Sturnella neglecta) habitat units. Mule deer and sharp-tailed grouse habitat units increased by 346.42 HUs and 470.62 HUs respectively over baseline (1999) survey results due largely to cessation of livestock grazing and subsequent passive restoration. In contrast, the western meadowlark generated slightly fewer habitat units in 2007 (-67.31) than in 1999, because of increased shrub cover, which lowers habitat suitability for that species.« less

Material matters: Analysis of density uncertainty in 3D printing and its consequences for radiation oncology.

PubMed

Craft, Daniel F; Kry, Stephen F; Balter, Peter; Salehpour, Mohammad; Woodward, Wendy; Howell, Rebecca M

2018-04-01

Using 3D printing to fabricate patient-specific devices such as tissue compensators, boluses, and phantoms is inexpensive and relatively simple. However, most 3D printing materials have not been well characterized, including their radiologic tissue equivalence. The purposes of this study were to (a) determine the variance in Hounsfield Units (HU) for printed objects, (b) determine if HU varies over time, and (c) calculate the clinical dose uncertainty caused by these material variations. For a sample of 10 printed blocks each of PLA, NinjaFlex, ABS, and Cheetah, the average HU and physical density were tracked at initial printing and over the course of 5 weeks, a typical timeframe for a standard course of radiotherapy. After initial printing, half the blocks were stored in open boxes, the other half in sealed bags with desiccant. Variances in HU and density over time were evaluated for the four materials. Various clinical photon and electron beams were used to evaluate potential errors in clinical depth dose as a function of assumptions made during treatment planning. The clinical depth error was defined as the distance between the correctly calculated 90% isodose line and the 90% isodose line calculated using clinically reasonable, but simplified, assumptions. The average HU measurements of individual blocks of PLA, ABS, NinjaFlex, and Cheetah varied by as much as 121, 30, 178, and 30 HU, respectively. The HU variation over 5 weeks was much smaller for all materials. The magnitude of clinical depth errors depended strongly on the material, energy, and assumptions, but some were as large as 9.0 mm. If proper quality assurance steps are taken, 3D printed objects can be used accurately and effectively in radiation therapy. It is critically important, however, that the properties of any material being used in patient care be well understood and accounted for. © 2018 American Association of Physicists in Medicine.

SU-C-204-02: Improved Patient-Specific Optimization of the Stopping Power Calibration for Proton Therapy Planning Using a Single Proton Radiography

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rinaldi, I; Ludwig Maximilian University, Garching, DE; Heidelberg University Hospital, Heidelberg, DE

2015-06-15

Purpose: We present an improved method to calculate patient-specific calibration curves to convert X-ray computed tomography (CT) Hounsfield Unit (HU) to relative stopping powers (RSP) for proton therapy treatment planning. Methods: By optimizing the HU-RSP calibration curve, the difference between a proton radiographic image and a digitally reconstructed X-ray radiography (DRR) is minimized. The feasibility of this approach has previously been demonstrated. This scenario assumes that all discrepancies between proton radiography and DRR originate from uncertainties in the HU-RSP curve. In reality, external factors cause imperfections in the proton radiography, such as misalignment compared to the DRR and unfaithful representationmore » of geometric structures (“blurring”). We analyze these effects based on synthetic datasets of anthropomorphic phantoms and suggest an extended optimization scheme which explicitly accounts for these effects. Performance of the method is been tested for various simulated irradiation parameters. The ultimate purpose of the optimization is to minimize uncertainties in the HU-RSP calibration curve. We therefore suggest and perform a thorough statistical treatment to quantify the accuracy of the optimized HU-RSP curve. Results: We demonstrate that without extending the optimization scheme, spatial blurring (equivalent to FWHM=3mm convolution) in the proton radiographies can cause up to 10% deviation between the optimized and the ground truth HU-RSP calibration curve. Instead, results obtained with our extended method reach 1% or better correspondence. We have further calculated gamma index maps for different acceptance levels. With DTA=0.5mm and RD=0.5%, a passing ratio of 100% is obtained with the extended method, while an optimization neglecting effects of spatial blurring only reach ∼90%. Conclusion: Our contribution underlines the potential of a single proton radiography to generate a patient-specific calibration curve and to improve dose delivery by optimizing the HU-RSP calibration curve as long as all sources of systematic incongruence are properly modeled.« less

SU-F-R-55: Early Detection of Treatment Induced Bone Marrow Injury During Chemoradiation Therapy Using Quantitative CT

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, X; Song, Y; Erickson, B

Purpose: Acute hematologic toxicity associated with bone marrow injury is a common complication of chemoradiation therapy (CRT) for pelvic malignancies. In this work, we investigate the feasibility of using quantitative CT to detect bone marrow injury during CRT. Methods: Daily CTs were acquired during routine CT-guided radiation therapy using a CT-on-rails for 15 cervical cancer patients. All patients treated with a radiation dose of 45.0 to 50.4 Gy in 1.8 Gy/fraction along with chemotherapy. For each patient, the contours of bone marrow were generated in L4, L5 and sacrum on the first daily CT and then populated to other dailymore » CTs by rigid registration using MIM (MIM Software Inc., Cleveland, OH) with manual editing if possible. A series of CT texture parameters, including Hunsfield Unit (HU) histogram, mean HU, entropy, energy, in bone marrow contours were calculated using MATLAB on each daily CT and were correlated with the completed blood counts (CBC) collected weekly for each patient. The correlations were analyzed with Pearson correlation tests. Results: For all patient data analyzed, mean HU in bone marrow decreased during CRT delivery. From the first to the last fraction the average mean HU reduction is 58.1 ± 13.6 HU (P<0.01). This decrease can be observed as early as after first 5 fractions and is strongly associated with the changes of most CBC quantities, such as the reductions of white and blood cell counts (r=0.97, P=0.001). The reduction of HU is spatially varied. Conclusion: Chemoradiation induced bone marrow injury can be detected during the delivery of CRT using quantitative CT. Chemoradiation results in reductions in mean HU, which are strongly associated with the change in the pretrial blood cell counts. Early detection of bone marrow injury with commonly available CT opens a door to improve bone marrow sparing, reducing risk of hematologic toxicity.« less

Effect of different CT scanners and settings on femoral failure loads calculated by finite element models.

PubMed

Eggermont, Florieke; Derikx, Loes C; Free, Jeffrey; van Leeuwen, Ruud; van der Linden, Yvette M; Verdonschot, Nico; Tanck, Esther

2018-03-06

In a multi-center patient study, using different CT scanners, CT-based finite element (FE) models are utilized to calculate failure loads of femora with metastases. Previous studies showed that using different CT scanners can result in different outcomes. This study aims to quantify the effects of (i) different CT scanners; (ii) different CT protocols with variations in slice thickness, field of view (FOV), and reconstruction kernel; and (iii) air between calibration phantom and patient, on Hounsfield Units (HU), bone mineral density (BMD), and FE failure load. Six cadaveric femora were scanned on four CT scanners. Scans were made with multiple CT protocols and with or without an air gap between the body model and calibration phantom. HU and calibrated BMD were determined in cortical and trabecular regions of interest. Non-linear isotropic FE models were constructed to calculate failure load. Mean differences between CT scanners varied up to 7% in cortical HU, 6% in trabecular HU, 6% in cortical BMD, 12% in trabecular BMD, and 17% in failure load. Changes in slice thickness and FOV had little effect (≤4%), while reconstruction kernels had a larger effect on HU (16%), BMD (17%), and failure load (9%). Air between the body model and calibration phantom slightly decreased the HU, BMD, and failure loads (≤8%). In conclusion, this study showed that quantitative analysis of CT images acquired with different CT scanners, and particularly reconstruction kernels, can induce relatively large differences in HU, BMD, and failure loads. Additionally, if possible, air artifacts should be avoided. © 2018 Orthopaedic Research Society. © 2018 The Authors. Journal of Orthopaedic Research® Published by Wiley Periodicals, Inc. on behalf of the Orthopaedic Research Society. J Orthop Res. © 2018 The Authors. Journal of Orthopaedic Research® Published by Wiley Periodicals, Inc. on behalf of the Orthopaedic Research Society.

Likelihood of Incomplete Kidney Tumor Ablation with Radio Frequency Energy: Degree of Enhancement Matters.

PubMed

Lay, Aaron H; Stewart, Jeremy; Canvasser, Noah E; Cadeddu, Jeffrey A; Gahan, Jeffrey C

2016-07-01

Larger size and clear cell histopathology are associated with worse outcomes for malignant renal tumors treated with radio frequency ablation. We hypothesize that greater tumor enhancement may be a risk factor for radio frequency ablation failure due to increased vascularity. A retrospective review of patients who underwent radio frequency ablation for renal tumors with contrast enhanced imaging available was performed. The change in Hounsfield units (HU) of the tumor from the noncontrast phase to the contrast enhanced arterial phase was calculated. Radio frequency ablation failure rates for biopsy confirmed malignant tumors were compared using the chi-squared test. Multivariate logistic analysis was performed to assess predictive variables for radio frequency ablation failure. Disease-free survival was calculated using Kaplan-Meier analysis. A total of 99 patients with biopsy confirmed malignant renal tumors and contrast enhanced imaging were identified. The incomplete ablation rate was significantly lower for tumors with enhancement less than 60 vs 60 HU or greater (0.0% vs 14.6%, p=0.005). On multivariate logistic regression analysis tumor enhancement 60 HU or greater (OR 1.14, p=0.008) remained a significant predictor of incomplete initial ablation. The 5-year disease-free survival for size less than 3 cm was 100% vs 69.2% for size 3 cm or greater (p <0.01), while 5-year disease-free survival for HU change less than 60 was 100% vs 92.4% for HU change 60 or greater (p=0.24). Biopsy confirmed malignant renal tumors, which exhibit a change in enhancement of 60 HU or greater, experience a higher rate of incomplete initial tumor ablation than tumors with enhancement less than 60 HU. Size 3 cm or greater portends worse 5-year disease-free survival after radio frequency ablation. The degree of enhancement should be considered when counseling patients before radio frequency ablation. Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Thrombopoietin: biology and clinical potentials.

PubMed

Miyazaki, H; Kato, T

1999-12-01

Thrombopoietin (TPO) is the principal physiologic regulator of platelet production. In vitro, TPO induces the growth of colony-forming units-megakaryocyte (CFU-MK) and the generation of mature polyploid megakaryocytes, which subsequently form extended cytoplasmic processes, termed proplatelets. On more differentiated CFU-MK, but not on megakaryocytes, TPO is critical for enhancing proplatelet formation. TPO has multilineage effects in hematopoiesis, not only stimulating megakaryocytopoiesis but also acting in synergy with other cytokines to enhance proliferation and survival of committed erythroid progenitors and primitive hematopoietic stem cells. Surface c-MPL, the receptor for TPO, defines a phenotype of hematopoietic stem cells with long-term repopulating ability. Treatment with various cytokine combinations, including TPO, results in an extensive ex vivo expansion of hematopoietic stem cells and blood cell precursors. In normal animals, pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF) or glycosylated TPO increases the number of bone marrow megakaryocytes and their progenitors and greatly enhance the production of morphologically and functionally normal platelets. In contrast, they have only minimal effects on peripheral white blood cell and red blood cell counts. PEG-rHuMGDF used alone markedly expands circulating levels of multiple types of hematopoietic progenitors, and its effect is enhanced in combination with granulocyte colony-stimulating factor (G-CSF). Although PEG-rHuMGDF augments platelet aggregation induced by agonists in vitro, it has no influence in an animal model of thrombus formation. PEG-rHuMGDF or glycosylated TPO has a profound effect in a variety of animal models of thrombocytopenia, including myelosuppressive therapy. PEG-rHuMGDF treatment accelerates multilineage hematopoietic recovery, effectively improving thrombocytopenia, and, in most models, neutropenia and anemia. The concurrent administration of PEG-rHuMGDF and G-CSF does not interfere with the in vivo activity of cytokines but rather has synergistic effects. To further accelerate hematopoietic recovery, PEG-rHuMGDF administration should start at the earliest time following myelosuppressive treatment; this time sensitivity may result from the presence of a greater number of residual hematopoietic progenitors in the bone marrow soon after treatment. Moreover, if a relatively large dose of PEG-rHuMGDF is administered, a single intravenous injection is fully effective in improving impaired hematopoiesis. This effectiveness appears to be related to the persistence of PEG-rHuMGDF in the circulation. The safety and efficacy of two forms of the recombinant hormone, PEG-rHuMDGF and glycosylated human full-length TPO produced in mammalian cells, are currently under clinical investigation.

Assessment of Severity of Ovine Smoke Inhalation Injury by Analysis of Computed Tomographic Scans

DTIC Science & Technology

2003-09-01

Computerized analysis of three- dimensional reconstructed scans was also performed, based on Hounsfield unit ranges: hyperinflated, 1,000 to 900; normal...the interactive segmentation function of the software. The pulmonary parenchyma was separated into four regions based on the Hounsfield unit (HU...SII) severity. Methods: Twenty anesthetized sheep underwent graded SII: group I, no smoke; group II, 5 smoke units ; group III, 10 units ; and group IV

Computed tomography of the liver and kidneys in glycogen storage disease.

PubMed

Doppman, J L; Cornblath, M; Dwyer, A J; Adams, A J; Girton, M E; Sidbury, J

1982-02-01

Glycogen, in concentrations encountered in von Gierke's disease, has computed tomography (CT) attenuation coefficients in the 50 to 70 Hounsfield unit (HU: 1,000 scale) range and accounts for the increased density of the liver. However, in eight patients with Type I glycogen storage disease, simultaneous hepatic infiltration with fat and glycogen led to a range of liver CT densities from 13 to 80 HU. Fatty infiltration may facilitate the demonstration of hepatic tumors in older patients with this disease. Half the patients showed increased attenuation coefficients of the renal cortex, indicating glycogen deposition in the kidneys.

Computed Tomographic Window Setting for Bronchial Measurement to Guide Double-Lumen Tube Size.

PubMed

Seo, Jeong-Hwa; Bae, Jinyoung; Paik, Hyesun; Koo, Chang-Hoon; Bahk, Jae-Hyon

2018-04-01

The bronchial diameter measured on computed tomography (CT) can be used to guide double-lumen tube (DLT) sizes objectively. The bronchus is known to be measured most accurately in the so-called bronchial CT window. The authors investigated whether using the bronchial window results in the selection of more appropriately sized DLTs than using the other windows. CT image analysis and prospective randomized study. Tertiary hospital. Adults receiving left-sided DLTs. The authors simulated selection of DLT sizes based on the left bronchial diameters measured in the lung (width 1,500 Hounsfield unit [HU] and level -700 HU), bronchial (1,000 HU and -450 HU), and mediastinal (400 HU and 25 HU) CT windows. Furthermore, patients were randomly assigned to undergo imaging with either the bronchial or mediastinal window to guide DLT sizes. Using the underwater seal technique, the authors assessed whether the DLT was appropriately sized, undersized, or oversized for the patient. On 130 CT images, the bronchial diameter (9.9 ± 1.2 mm v 10.5 ± 1.3 mm v 11.7 ± 1.3 mm) and the selected DLT size were different in the lung, bronchial, and mediastinal windows, respectively (p < 0.001). In 13 patients (17%), the bronchial diameter measured in the lung window suggested too small DLTs (28 Fr) for adults. In the prospective study, oversized tubes were chosen less frequently in the bronchial window than in the mediastinal window (6/110 v 23/111; risk ratio 0.38; 95% CI 0.19-0.79; p = 0.003). No tubes were undersized after measurements in these two windows. The bronchial measurement in the bronchial window guided more appropriately sized DLTs compared with the lung or mediastinal windows. Copyright © 2017 Elsevier Inc. All rights reserved.

Interactions between Human Norovirus Surrogates and Acanthamoeba spp.

PubMed Central

Hsueh, Tun-Yun

2015-01-01

Human noroviruses (HuNoVs) are the most common cause of food-borne disease outbreaks, as well as virus-related waterborne disease outbreaks in the United States. Here, we hypothesize that common free-living amoebae (FLA)—ubiquitous in the environment, known to interact with pathogens, and frequently isolated from water and fresh produce—could potentially act as reservoirs of HuNoV and facilitate the environmental transmission of HuNoVs. To investigate FLA as reservoirs for HuNoV, the interactions between two Acanthamoeba species, A. castellanii and A. polyphaga, as well as two HuNoV surrogates, murine norovirus type 1 (MNV-1) and feline calicivirus (FCV), were evaluated. The results showed that after 1 h of amoeba-virus incubation at 25°C, 490 and 337 PFU of MNV-1/ml were recovered from A. castellanii and A. polyphaga, respectively, while only few or no FCVs were detected. In addition, prolonged interaction of MNV-1 with amoebae was investigated for a period of 8 days, and MNV-1 was demonstrated to remain stable at around 200 PFU/ml from day 2 to day 8 after virus inoculation in A. castellanii. Moreover, after a complete amoeba life cycle (i.e., encystment and excystment), infectious viruses could still be detected. To determine the location of virus associated with amoebae, immunofluorescence experiments were performed and showed MNV-1 transitioning from the amoeba surface to inside the amoeba over a 24-h period. These results are significant to the understanding of how HuNoVs may interact with other microorganisms in the environment in order to aid in its persistence and survival, as well as potential transmission in water and to vulnerable food products such as fresh produce. PMID:25841006

Imaging-based assessment of the mineral composition of urinary stones: an in vitro study of the combination of hounsfield unit measurement in noncontrast helical computerized tomography and the twinkling artifact in color Doppler ultrasound.

PubMed

Hassani, Hakim; Raynal, Gauthier; Spie, Romain; Daudon, Michel; Vallée, Jean-Noël

2012-05-01

We evaluated the value of combining noncontrast helical computerized tomography (NCHCT) and color Doppler ultrasound in the assessment of the composition of urinary stones. In vitro, we studied 120 stones of known composition, that separate into the five main types: 18 calcium oxalate monohydrate (COM) stones, 41 calcium oxalate dihydrate (COD) stones, 24 uric acid stones, 25 calcium phosphate stones and 12 cystine calculi. Stones were characterized in terms of their Hounsfield density (HU) in NCHCT and the presence of a twinkling artifact (TA) in color Doppler ultrasound. There were statistically significant HU differences between calcium and non-calcium stones (p < 0.001), calcium oxalate stones and calcium phosphate stones (p < 0.001) and uric acid stones and cystine calculi (p < 0.001) but not between COM and COD stones (p = 0.786). Hence, the HU was a predictive factor of the composition of all types of stones, other than for COM and COD stones within the calcium oxalate class (p > 0.05). We found that the TA does not enable differentiation between calcium and non-calcium stones (p > 0.999), calcium oxalate stones and calcium phosphate stones (p = 0.15), or uric acid stones and cystine calculi (p = 0.079). However, it did reveal a significant difference between COM and COD stones (p = 0.002). The absence of a TA is a predictive factor for the presence of COM stones (p = 0.008). Hence, the association of NCHCT and Doppler enables the accurate classification of the five types of stones in vitro. Copyright © 2012 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Is 18F-FDG PET/CT useful for distinguishing between primary thyroid lymphoma and chronic thyroiditis?

PubMed

Nakadate, Masashi; Yoshida, Katsuya; Ishii, Akihiro; Koizumi, Masayuki; Tochigi, Naobumi; Suzuki, Yoshio; Ryu, Yoshiharu; Nakagawa, Tassei; Umehara, Isao; Shibuya, Hitoshi

2013-09-01

This study aims to investigate the usefulness of (18)F-FDG PET/CT for distinguishing between primary thyroid lymphoma (PTL) and chronic thyroiditis. We retrospectively reviewed the data of 196 patients with diffuse (18)F-FDG uptake of the thyroid gland and enrolled patients who were diagnosed as having PTL or chronic thyroiditis based on the medical records, pathological findings, and laboratory data. The enrolled patients comprised 10 PTL patients (M/F = 4:6) and 51 chronic thyroiditis patients (M/F = 8:43). Images had been acquired on a PET/CT scanner at 100 minutes after intravenous injection of (18)F-FDG. The PTL group consisted of 7 patients with diffuse large B-cell lymphoma (DLBCL) and 3 with mucosa-associated lymphoid tissue (MALT) lymphoma. The maximum standardized uptake value (SUV(max)) was significantly higher in the PTL group than that in the chronic thyroiditis group (25.3 ± 8.0 and 7.4 ± 3.2, P < 0.001). On the other hand, the CT density (Hounsfield unit: HU) was significantly lower in the PTL group than that in the chronic thyroiditis group (46.1 ± 7.0 HU and 62.1 ± 6.9 HU, P < 0.001). Within the PTL group, the SUV(max) was significantly higher in the cases of DLBCL than in those of MALT lymphoma (29.0 ± 6.4 and 16.7 ± 2.3, P = 0.017). The SUV(max) was significantly higher and the CT density was significantly lower in PTL as compared with those in chronic thyroiditis. Thus, (18)F-FDG PET/CT may be useful for distinguishing between PTL and chronic thyroiditis.

Comparison of volumetric breast density estimations from mammography and thorax CT

NASA Astrophysics Data System (ADS)

Geeraert, N.; Klausz, R.; Cockmartin, L.; Muller, S.; Bosmans, H.; Bloch, I.

2014-08-01

Breast density has become an important issue in current breast cancer screening, both as a recognized risk factor for breast cancer and by decreasing screening efficiency by the masking effect. Different qualitative and quantitative methods have been proposed to evaluate area-based breast density and volumetric breast density (VBD). We propose a validation method comparing the computation of VBD obtained from digital mammographic images (VBDMX) with the computation of VBD from thorax CT images (VBDCT). We computed VBDMX by applying a conversion function to the pixel values in the mammographic images, based on models determined from images of breast equivalent material. VBDCT is computed from the average Hounsfield Unit (HU) over the manually delineated breast volume in the CT images. This average HU is then compared to the HU of adipose and fibroglandular tissues from patient images. The VBDMX method was applied to 663 mammographic patient images taken on two Siemens Inspiration (hospL) and one GE Senographe Essential (hospJ). For the comparison study, we collected images from patients who had a thorax CT and a mammography screening exam within the same year. In total, thorax CT images corresponding to 40 breasts (hospL) and 47 breasts (hospJ) were retrieved. Averaged over the 663 mammographic images the median VBDMX was 14.7% . The density distribution and the inverse correlation between VBDMX and breast thickness were found as expected. The average difference between VBDMX and VBDCT is smaller for hospJ (4%) than for hospL (10%). This study shows the possibility to compare VBDMX with the VBD from thorax CT exams, without additional examinations. In spite of the limitations caused by poorly defined breast limits, the calibration of mammographic images to local VBD provides opportunities for further quantitative evaluations.

SU-F-T-300: Impact of Electron Density Modeling of ArcCHECK Cylindricaldiode Array On 3DVH Patient Specific QA Software Tool Analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Patwe, P; Mhatre, V; Dandekar, P

Purpose: 3DVH software is a patient specific quality assurance tool which estimates the 3D dose to the patient specific geometry with the help of Planned Dose Perturbation algorithm. The purpose of this study is to evaluate the impact of HU value of ArcCHECK phantom entered in Eclipse TPS on 3D dose & DVH QA analysis. Methods: Manufacturer of ArcCHECK phantom provides CT data set of phantom & recommends considering it as a homogeneous phantom with electron density (1.19 gm/cc or 282 HU) close to PMMA. We performed this study on Eclipse TPS (V13, VMS) & trueBEAM STx VMS Linac &more » ArcCHECK phantom (SNC). Plans were generated for 6MV photon beam, 20cm×20cm field size at isocentre & SPD (Source to phantom distance) of 86.7 cm to deliver 100cGy at isocentre. 3DVH software requires patients DICOM data generated by TPS & plan delivered on ArcCHECK phantom. Plans were generated in TPS by assigning different HU values to phantom. We analyzed gamma index & the dose profile for all plans along vertical down direction of beam’s central axis for Entry, Exit & Isocentre dose. Results: The global gamma passing rate (2% & 2mm) for manufacturer recommended HU value 282 was 96.3%. Detector entry, Isocentre & detector exit Doses were 1.9048 (1.9270), 1.00(1.0199) & 0.5078(0.527) Gy for TPS (Measured) respectively.The global gamma passing rate for electron density 1.1302 gm/cc was 98.6%. Detector entry, Isocentre & detector exit Doses were 1.8714 (1.8873), 1.00(0.9988) & 0.5211(0.516) Gy for TPS (Measured) respectively. Conclusion: Electron density value assigned by manufacturer does not hold true for every user. Proper modeling of electron density of ArcCHECK in TPS is essential to avoid systematic error in dose calculation of patient specific QA.« less

Comparison between In-house developed and Diamond commercial software for patient specific independent monitor unit calculation and verification with heterogeneity corrections.

PubMed

Kuppusamy, Vijayalakshmi; Nagarajan, Vivekanandan; Jeevanandam, Prakash; Murugan, Lavanya

2016-02-01

The study was aimed to compare two different monitor unit (MU) or dose verification software in volumetric modulated arc therapy (VMAT) using modified Clarkson's integration technique for 6 MV photons beams. In-house Excel Spreadsheet based monitor unit verification calculation (MUVC) program and PTW's DIAMOND secondary check software (SCS), version-6 were used as a secondary check to verify the monitor unit (MU) or dose calculated by treatment planning system (TPS). In this study 180 patients were grouped into 61 head and neck, 39 thorax and 80 pelvic sites. Verification plans are created using PTW OCTAVIUS-4D phantom and also measured using 729 detector chamber and array with isocentre as the suitable point of measurement for each field. In the analysis of 154 clinically approved VMAT plans with isocentre at a region above -350 HU, using heterogeneity corrections, In-house Spreadsheet based MUVC program and Diamond SCS showed good agreement TPS. The overall percentage average deviations for all sites were (-0.93% + 1.59%) and (1.37% + 2.72%) for In-house Excel Spreadsheet based MUVC program and Diamond SCS respectively. For 26 clinically approved VMAT plans with isocentre at a region below -350 HU showed higher variations for both In-house Spreadsheet based MUVC program and Diamond SCS. It can be concluded that for patient specific quality assurance (QA), the In-house Excel Spreadsheet based MUVC program and Diamond SCS can be used as a simple and fast accompanying to measurement based verification for plans with isocentre at a region above -350 HU. Copyright © 2016 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

SU-E-J-26: Analysis of Image Quality in CBCT QA Using a Treatment Planning System

DOE Office of Scientific and Technical Information (OSTI.GOV)

Xu, M

2014-06-01

Purpose: The objective of this study is to propose an alternative QA technique that analyzes imaging quality(IQ) in CBCT-QA processing. Methods: A catphan phantom was used to take CT imaging data set that were imported into a treatment planning system - Eclipse. The image quality was analyzed in terms of in-slice geometry resolution, Hounsfield numbers(HU) accuracy, mean-slice thickness, edge-to-center uniformity, low contrast resolution, and high contrast spatial resolution in Eclipse workstation. The CBCT-QA was also analyzed by OBI-workstation and a commercial software. Comparison was made to evaluation feasibility in a TPS environment. Results: The analysis of IQ was conducted inmore » Eclipse v10.0 TPS. In-slice geometric resolution was measured between 2-rods in section CTP404 and repeated for all 4 rods with the difference between expected and measured values less than +/−0.1 cm. For HU, the difference between expected and measured values in HU was found much less than +/−40. Mean slice thickness measured by a distance on the wire proportional to scanner increment multiplying by a factor of 0.42. After repeating measurements to 4 wires, the average difference between expected and measured values was less +/−0.124 mm in slice thickness. HU uniformity was measured in section CTP486 with the tolerance less than +/−40 HU. Low contrast resolution in section CTP515 and high contrast resolution in section CTP528 were found to be 7 disks in diameter of 4 mm and 6 lp/cm, respectively. Eclipse TPS results indicated a good agreement to those obtained in OBI workstation and ImagePro software for major parameters. Conclusion: An analysis of IQ was proposed as an alternative CBCT QA processing. Based upon measured data assessment, proposed method was accurate and consistent to IQ evaluation and TG142 guideline. The approach was to utilize TPS resource, which can be valuable to re-planning, verification, and delivery in adaptive therapy.« less

Intravascular enhancement with identical iodine delivery rate using different iodine contrast media in a circulation phantom.

PubMed

Mihl, Casper; Wildberger, Joachim E; Jurencak, Tomas; Yanniello, Michael J; Nijssen, Estelle C; Kalafut, John F; Nalbantov, Georgi; Mühlenbruch, Georg; Behrendt, Florian F; Das, Marco

2013-11-01

Both iodine delivery rate (IDR) and iodine concentration are decisive factors for vascular enhancement in computed tomographic angiography. It is unclear, however, whether the use of high-iodine concentration contrast media is beneficial to lower iodine concentrations when IDR is kept identical. This study evaluates the effect of using different iodine concentrations on intravascular attenuation in a circulation phantom while maintaining a constant IDR. A circulation phantom with a low-pressure venous compartment and a high-pressure arterial compartment simulating physiological circulation parameters was used (heart rate, 60 beats per minute; stroke volume, 60 mL; blood pressure, 120/80 mm Hg). Maintaining a constant IDR (2.0 g/s) and a constant total iodine load (20 g), prewarmed (37°C) contrast media with differing iodine concentrations (240-400 mg/mL) were injected into the phantom using a double-headed power injector. Serial computed tomographic scans at the level of the ascending aorta (AA), the descending aorta (DA), and the left main coronary artery (LM) were obtained. Total amount of contrast volume (milliliters), iodine delivery (grams of iodine), peak flow rate (milliliter per second), and intravascular pressure (pounds per square inch) were monitored using a dedicated data acquisition program. Attenuation values in the AA, the DA, and the LM were constantly measured (Hounsfield unit [HU]). In addition, time-enhancement curves, aortic peak enhancement, and time to peak were determined. All contrast injection protocols resulted in similar attenuation values: the AA (516 [11] to 531 [37] HU), the DA (514 [17] to 531 [32] HU), and the LM (490 [10] to 507 [17] HU). No significant differences were found between the AA, the DA, and the LM for either peak enhancement (all P > 0.05) or mean time to peak (AA, 19.4 [0.58] to 20.1 [1.05] seconds; DA, 21.1 [1.0] to 21.4 [1.15] seconds; LM, 19.8 [0.58] to 20.1 [1.05] seconds). This phantom study demonstrates that constant injection parameters (IDR, overall iodine load) lead to robust enhancement patterns, regardless of the contrast material used. Higher iodine concentration itself does not lead to higher attenuation levels. These results may stimulate a shift in paradigm toward clinical usage of contrast media with lower iodine concentrations (eg, 240 mg iodine/mL) in individual tailored contrast protocols. The use of low-iodine concentration contrast media is desirable because of the lower viscosity and the resulting lower injection pressure.

Renal Cyst Pseudoenhancement: Intraindividual Comparison Between Virtual Monochromatic Spectral Images and Conventional Polychromatic 120-kVp Images Obtained During the Same CT Examination and Comparisons Among Images Reconstructed Using Filtered Back Projection, Adaptive Statistical Iterative Reconstruction, and Model-Based Iterative Reconstruction

PubMed Central

Yamada, Yoshitake; Yamada, Minoru; Sugisawa, Koichi; Akita, Hirotaka; Shiomi, Eisuke; Abe, Takayuki; Okuda, Shigeo; Jinzaki, Masahiro

2015-01-01

Abstract The purpose of this study was to compare renal cyst pseudoenhancement between virtual monochromatic spectral (VMS) and conventional polychromatic 120-kVp images obtained during the same abdominal computed tomography (CT) examination and among images reconstructed using filtered back projection (FBP), adaptive statistical iterative reconstruction (ASIR), and model-based iterative reconstruction (MBIR). Our institutional review board approved this prospective study; each participant provided written informed consent. Thirty-one patients (19 men, 12 women; age range, 59–85 years; mean age, 73.2 ± 5.5 years) with renal cysts underwent unenhanced 120-kVp CT followed by sequential fast kVp-switching dual-energy (80/140 kVp) and 120-kVp abdominal enhanced CT in the nephrographic phase over a 10-cm scan length with a random acquisition order and 4.5-second intervals. Fifty-one renal cysts (maximal diameter, 18.0 ± 14.7 mm [range, 4–61 mm]) were identified. The CT attenuation values of the cysts as well as of the kidneys were measured on the unenhanced images, enhanced VMS images (at 70 keV) reconstructed using FBP and ASIR from dual-energy data, and enhanced 120-kVp images reconstructed using FBP, ASIR, and MBIR. The results were analyzed using the mixed-effects model and paired t test with Bonferroni correction. The attenuation increases (pseudoenhancement) of the renal cysts on the VMS images reconstructed using FBP/ASIR (least square mean, 5.0/6.0 Hounsfield units [HU]; 95% confidence interval, 2.6–7.4/3.6–8.4 HU) were significantly lower than those on the conventional 120-kVp images reconstructed using FBP/ASIR/MBIR (least square mean, 12.1/12.8/11.8 HU; 95% confidence interval, 9.8–14.5/10.4–15.1/9.4–14.2 HU) (all P < .001); on the other hand, the CT attenuation values of the kidneys on the VMS images were comparable to those on the 120-kVp images. Regardless of the reconstruction algorithm, 70-keV VMS images showed a lower degree of pseudoenhancement of renal cysts than 120-kVp images, while maintaining kidney contrast enhancement comparable to that on 120-kVp images. PMID:25881852

Archaeological Investigations at Site 45-OK-258, Chief Joseph Dam Project, Washington.

DTIC Science & Technology

1985-01-01

skull - 6 1 - - - 3 - - - - - - mandible 1 6 1 12 7 scepuLe - 2 - 1 - - 3 - - hu~ mrus dista- 1 3 - - - - 3 - - - - radius praximaIL - - - - - 1...unit level materials from the other tesiing unit (3N64W). Bitterbrush wood was not utilized for tools or other artifacts; the southern Okanogan used it

An anthropomorphic abdominal phantom for deformable image registration accuracy validation in adaptive radiation therapy.

PubMed

Liao, Yuliang; Wang, Linjing; Xu, Xiangdong; Chen, Haibin; Chen, Jiawei; Zhang, Guoqian; Lei, Huaiyu; Wang, Ruihao; Zhang, Shuxu; Gu, Xuejun; Zhen, Xin; Zhou, Linghong

2017-06-01

To design and construct a three-dimensional (3D) anthropomorphic abdominal phantom for geometric accuracy and dose summation accuracy evaluations of deformable image registration (DIR) algorithms for adaptive radiation therapy (ART). Organ molds, including liver, kidney, spleen, stomach, vertebra, and two metastasis tumors, were 3D printed using contours from an ovarian cancer patient. The organ molds were molded with deformable gels made of different mixtures of polyvinyl chloride (PVC) and the softener dioctyl terephthalate. Gels with different densities were obtained by a polynomial fitting curve that described the relation between the Hounsfield unit (HU) and PVC-softener blending ratio. The rigid vertebras were constructed by molding of white cement and cellulose pulp. The final abdominal phantom was assembled by arranging all the fabricated organs inside a hollow dummy according to their anatomies, and sealed by deformable gel with averaged HU of muscle and fat. Fiducial landmarks were embedded inside the phantom for spatial accuracy and dose accumulation accuracy studies. Two channels were excavated to facilitate ionization chamber insertion for dosimetric measurements. Phantom properties such as deformable gel elasticity and HU stability were studied. The dosimetric measurement accuracy in the phantom was performed, and the DIR accuracies of three DIR algorithms available in the open source DIR toolkit-DIRART were also validated. The constructed deformable gel showed elastic behavior and was stable in HU values over times, proving to be a practical material for the deformable phantom. The constructed abdominal phantom consisted of realistic anatomies in terms of both anatomical shapes and densities when compared with its reference patient. The dosimetric measurements showed a good agreement with the calculated doses from the treatment planning system. Fiducial-based accuracy analysis conducted on the constructed phantom demonstrated the feasibility of applying the phantom for organ-wise DIR accuracy assessment. We have designed and constructed an anthropomorphic abdominal deformable phantom with satisfactory elastic property, realistic organ density, and anatomy. This physical phantom can be used for routine validations of DIR geometric accuracy and dose accumulation accuracy in ART. © 2017 American Association of Physicists in Medicine.

Material decomposition images generated from spectral CT: detectability of urinary calculi and influencing factors.

PubMed

Lv, Peijie; Zhang, Yonggao; Liu, Jie; Ji, Lijuan; Chen, Yan; Gao, Jianbo

2014-01-01

To evaluate the detectability of urinary calculi on material decomposition (MD) images generated from spectral computed tomography (CT) and identify the influencing factors. Forty-six patients were examined with true nonenhanced (TNE) CT and spectral CT urography in the excretory phase. The contrast medium was removed from excretory phase images using water-based (WB) and calcium-based (CaB) MD analysis. The sensitivity for detection on WB and CaB images was evaluated using TNE results as the reference standard. The signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) on MD images were evaluated. Using logistic regression, the influences of image noise, attenuation, stone size, and patient's body mass index (BMI) were assessed. Threshold values with maximal sensitivity and specificity were calculated by means of receiver operating characteristic analyses. One hundred thirty-six calculi were detected on TNE images; 98 calculi were identified on WB images (sensitivity, 72.06%) and 101 calculi on CaB images (sensitivity, 74.26%). Sensitivities were 76.92% for the 3-5-mm stones and 84.51% for the 5-mm or larger stones on both WB and CaB images but reduced to 46.15% on WB images and 53.85% on CaB images for small calculi (<3 mm). Compared to WB images, CaB images showed lower image noise, higher SNR but similar CNR. Larger stone sizes (both >2.71 mm on WB and CaB) and greater CT attenuation (>280 Hounsfield units [HU] on WB, >215 HU on CaB) of the urinary stones were significantly associated with higher stone visibility rates on WB and CaB images (P ≤ .003). Image noise and BMI showed no impact on the stone detection. MD images generated from spectral CT showed good reliability for the detection of large (>2.71 mm) and hyperattenuating (>280 HU on WB, >215 HU on CaB) urinary calculi. Copyright © 2014 AUR. Published by Elsevier Inc. All rights reserved.

Biomechanics of North Atlantic Right Whale Bone: Mandibular Fracture as a Fatal Endpoint for Blunt Vessel-Whale Collision Modeling

DTIC Science & Technology

2007-09-01

Calibration curves for CT number ( Hounsfield unit )s vs. mineral density (g /c c...12 3 Figure 3.4. Calibration curves for CT number ( Hounsfield units ) vs. apparent density (g /c c...named Hounsfield units (HU) after Sir Godfrey Hounsfield . The CT number is K([i- iw]/pw), where K = a magnifying constant, which depends on the make of CT

DECT evaluation of noncalcified coronary artery plaque

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ravanfar Haghighi, Rezvan; Chatterjee, S.; Tabin, Milo

2015-10-15

Purpose: Composition of the coronary artery plaque is known to have critical role in heart attack. While calcified plaque can easily be diagnosed by conventional CT, it fails to distinguish between fibrous and lipid rich plaques. In the present paper, the authors discuss the experimental techniques and obtain a numerical algorithm by which the electron density (ρ{sub e}) and the effective atomic number (Z{sub eff}) can be obtained from the dual energy computed tomography (DECT) data. The idea is to use this inversion method to characterize and distinguish between the lipid and fibrous coronary artery plaques. Methods: For the purposemore » of calibration of the CT machine, the authors prepare aqueous samples whose calculated values of (ρ{sub e}, Z{sub eff}) lie in the range of (2.65 × 10{sup 23} ≤ ρ{sub e} ≤ 3.64 × 10{sup 23}/cm{sup 3}) and (6.80 ≤ Z{sub eff} ≤ 8.90). The authors fill the phantom with these known samples and experimentally determine HU(V{sub 1}) and HU(V{sub 2}), with V{sub 1},V{sub 2} = 100 and 140 kVp, for the same pixels and thus determine the coefficients of inversion that allow us to determine (ρ{sub e}, Z{sub eff}) from the DECT data. The HU(100) and HU(140) for the coronary artery plaque are obtained by filling the channel of the coronary artery with a viscous solution of methyl cellulose in water, containing 2% contrast. These (ρ{sub e}, Z{sub eff}) values of the coronary artery plaque are used for their characterization on the basis of theoretical models of atomic compositions of the plaque materials. These results are compared with histopathological report. Results: The authors find that the calibration gives ρ{sub e} with an accuracy of ±3.5% while Z{sub eff} is found within ±1% of the actual value, the confidence being 95%. The HU(100) and HU(140) are found to be considerably different for the same plaque at the same position and there is a linear trend between these two HU values. It is noted that pure lipid type plaques are practically nonexistent, and microcalcification, as observed in histopathology, has to be taken into account to explain the nature of the observed (ρ{sub e}, Z{sub eff}) data. This also enables us to judge the composition of the plaque in terms of basic model which considers the plaque to be composed of fibres, lipids, and microcalcification. Conclusions: This simple and reliable method has the potential as an effective modality to investigate the composition of noncalcified coronary artery plaques and thus help in their characterization. In this inversion method, (ρ{sub e}, Z{sub eff}) of the scanned sample can be found by eliminating the effects of the CT machine and also by ensuring that the determination of the two unknowns (ρ{sub e}, Z{sub eff}) does not interfere with each other and the nature of the plaque can be identified in terms of a three component model.« less

Bone quality evaluation at dental implant site using multislice CT, micro-CT, and cone beam CT.

PubMed

Parsa, Azin; Ibrahim, Norliza; Hassan, Bassam; van der Stelt, Paul; Wismeijer, Daniel

2015-01-01

The first purpose of this study was to analyze the correlation between bone volume fraction (BV/TV) and calibrated radiographic bone density Hounsfield units (HU) in human jaws, derived from micro-CT and multislice computed tomography (MSCT), respectively. The second aim was to assess the accuracy of cone beam computed tomography (CBCT) in evaluating trabecular bone density and microstructure using MSCT and micro-CT, respectively, as reference gold standards. Twenty partially edentulous human mandibular cadavers were scanned by three types of CT modalities: MSCT (Philips, Best, the Netherlands), CBCT (3D Accuitomo 170, J Morita, Kyoto, Japan), and micro-CT (SkyScan 1173, Kontich, Belgium). Image analysis was performed using Amira (v4.1, Visage Imaging Inc., Carlsbad, CA, USA), 3Diagnosis (v5.3.1, 3diemme, Cantu, Italy), Geomagic (studio(®) 2012, Morrisville, NC, USA), and CTAn (v1.11, SkyScan). MSCT, CBCT, and micro-CT scans of each mandible were matched to select the exact region of interest (ROI). MSCT HU, micro-CT BV/TV, and CBCT gray value and bone volume fraction of each ROI were derived. Statistical analysis was performed to assess the correlations between corresponding measurement parameters. Strong correlations were observed between CBCT and MSCT density (r = 0.89) and between CBCT and micro-CT BV/TV measurements (r = 0.82). Excellent correlation was observed between MSCT HU and micro-CT BV/TV (r = 0.91). However, significant differences were found between all comparisons pairs (P < 0.001) except for mean measurement between CBCT BV/TV and micro-CT BV/TV (P = 0.147). An excellent correlation exists between bone volume fraction and bone density as assessed on micro-CT and MSCT, respectively. This suggests that bone density measurements could be used to estimate bone microstructural parameters. A strong correlation also was found between CBCT gray values and BV/TV and their gold standards, suggesting the potential of this modality in bone quality assessment at implant site. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

SU-G-BRB-01: A Novel 3D Printed Patient-Specific Phantom for Spine SBRT Quality Assurance: Comparison of 3D Printing Techniques

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lee, S; Kim, M; Lee, M

Purpose: The novel 3 dimensional (3D)-printed spine quality assurance (QA) phantoms generated by two different 3D-printing technologies, digital light processing (DLP) and Polyjet, were developed and evaluated for spine stereotactic body radiation treatment (SBRT). Methods: The developed 3D-printed spine QA phantom consisted of an acrylic body and a 3D-printed spine phantom. DLP and Polyjet 3D printers using the high-density acrylic polymer were employed to produce spine-shaped phantoms based on CT images. To verify dosimetric effects, the novel phantom was made it enable to insert films between each slabs of acrylic body phantom. Also, for measuring internal dose of spine, 3D-printedmore » spine phantom was designed as divided laterally exactly in half. Image fusion was performed to evaluate the reproducibility of our phantom, and the Hounsfield unit (HU) was measured based on each CT image. Intensity-modulated radiotherapy plans to deliver a fraction of a 16 Gy dose to a planning target volume (PTV) based on the two 3D-printing techniques were compared for target coverage and normal organ-sparing. Results: Image fusion demonstrated good reproducibility of the fabricated spine QA phantom. The HU values of the DLP- and Polyjet-printed spine vertebrae differed by 54.3 on average. The PTV Dmax dose for the DLP-generated phantom was about 1.488 Gy higher than for the Polyjet-generated phantom. The organs at risk received a lower dose when the DLP technique was used than when the Polyjet technique was used. Conclusion: This study confirmed that a novel 3D-printed phantom mimicking a high-density organ can be created based on CT images, and that a developed 3D-printed spine phantom could be utilized in patient-specific QA for SBRT. Despite using the same main material, DLP and Polyjet yielded different HU values. Therefore, the printing technique and materials must be carefully chosen in order to accurately produce a patient-specific QA phantom.« less

SU-F-J-220: Micro-CT Based Quantification of Mouse Brain Vasculature: The Effects of Acquisition Technique and Contrast Material

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tipton, C; Lamba, M; Qi, Z

Purpose: Cognitive impairment from radiation therapy to the brain may be linked to the loss of total blood volume in the brain. To account for brain injury, it is crucial to develop an understanding of blood volume loss as a result of radiation therapy. This study investigates µCT based quantification of mouse brain vasculature, focusing on the effect of acquisition technique and contrast material. Methods: Four mice were scanned on a µCT scanner (Siemens Inveon). The reconstructed voxel size was 18µm3 and all protocols were Hounsfield Unit (HU) calibrated. The mice were injected with 40mg of gold nanoparticles (MediLumine) ormore » 100µl of Exitron 12000 (Miltenyi Biotec). Two acquisition techniques were also performed. A single kVp technique scanned the mouse once using an x-ray beam of 80kVp and segmentation was completed based on a threshold of HU values. The dual kVp technique scanned the mouse twice using 50kVp and 80kVp, this segmentation was based on the ratio of the HU value of the two kVps. After image reconstruction and segmentation, the brain blood volume was determined as a percentage of the total brain volume. Results: For the single kVp acquisition at 80kVp, the brain blood volume had an average of 3.5% for gold and 4.0% for Exitron 12000. Also at 80kVp, the contrast-noise ratio was significantly better for images acquired with the gold nanoparticles (2.0) than for those acquired with the Exitron 12000 (1.4). The dual kVp acquisition shows improved separation of skull from vasculature, but increased image noise. Conclusion: In summary, the effects of acquisition technique and contrast material for quantification of mouse brain vasculature showed that gold nanoparticles produced more consistent segmentation of brain vasculature than Exitron 12000. Also, dual kVp acquisition may improve the accuracy of brain vasculature quantification, although the effect of noise amplification warrants further study.« less

Hydroxyurea inhibits parvovirus B19 replication in erythroid progenitor cells.

PubMed

Bonvicini, Francesca; Bua, Gloria; Conti, Ilaria; Manaresi, Elisabetta; Gallinella, Giorgio

2017-07-15

Parvovirus B19 (B19V) infection is restricted to erythroid progenitor cells (EPCs) of the human bone marrow, leading to transient arrest of erythropoiesis and severe complications mainly in subjects with underlying hematological disorders or with immune system deficits. Currently, there are no specific antiviral drugs for B19V treatment, but identification of compounds inhibiting B19V replication can be pursued by a drug repositioning strategy. In this frame, the present study investigates the activity of hydroxyurea (HU), the only disease-modifying therapy approved for sickle cell disease (SCD), towards B19V replication in the two relevant cellular systems, the UT7/EpoS1 cell line and EPCs. Results demonstrate that HU inhibits B19V replication with EC 50 values of 96.2µM and 147.1µM in UT7/EpoS1 and EPCs, respectively, providing experimental evidence of the antiviral activity of HU towards B19V replication, and confirming the efficacy of a drug discovery process by drug repositioning strategy. The antiviral activity occurs in vitro at concentrations lower than those affecting cellular DNA replication and viability, and at levels measured in plasma samples of SCD patients undergoing HU therapy. HU might determine a dual beneficial effect on SCD patients, not only for the treatment of the disease but also towards a virus responsible for severe complications. Copyright © 2017 Elsevier Inc. All rights reserved.

Alveolar Soft Part Sarcoma Presenting as Hypervascular Adrenal Metastasis

PubMed Central

Goroshi, Manjunath; Lila, Anurag R.; Bandgar, Tushar; Shah, Nalini S.

2018-01-01

Hypervascular adrenal masses include pheochromocytoma, metastases caused by clear renal cell carcinoma/hepatocellular carcinoma. Alveolar soft part sarcoma (ASPS) causing hypervascular metastases is not described in the literature. Here, we describe the first case of ASPS presenting as hypervascular metastasis. Our case was a 23-year-old male incidentally detected right adrenal mass during the evaluation of pain in the abdomen. On computed tomography (CT), adrenal mass showed bright enhancement in early arterial phase (unenhanced Hounsfield unit [HU]-45.3; arterial phase HU-158.2). 18- flurodeoxyglucose positron emission tomography/CT showed multiple lesions and was confirmed histologically to be due to ASPS. PMID:29398970

Georgetown University and Hampton University Prostate Cancer Undergraduate Fellowship Program

DTIC Science & Technology

2014-09-01

HU-GU Fellow Summer 2013 HU Class of 2015 Kimiko Krieger HU-GU Fellow Summer 2013 HU Class of 2014 Nathan Wilson HU-GU Fellow Summer 2013 HU Class...Tiffany Lumpkin HU-GU Fellow Summer 2010 Class of 2012; Johns Hopkins MS Biotechnology 2013 Zerin Scales HU-GU Fellow Summer 2010 Class of 2013

A new cannabinoid CB2 receptor agonist HU-910 attenuates oxidative stress, inflammation and cell death associated with hepatic ischaemia/reperfusion injury

PubMed Central

Horváth, Bėla; Magid, Lital; Mukhopadhyay, Partha; Bátkai, Sándor; Rajesh, Mohanraj; Park, Ogyi; Tanchian, Galin; Gao, Rachel Y; Goodfellow, Catherine E; Glass, Michelle; Mechoulam, Raphael; Pacher, Pál

2012-01-01

BACKGROUND AND PURPOSE Cannabinoid CB2 receptor activation has been reported to attenuate myocardial, cerebral and hepatic ischaemia-reperfusion (I/R) injury. EXPERIMENTAL APPROACH We have investigated the effects of a novel CB2 receptor agonist ((1S,4R)-2-(2,6-dimethoxy-4-(2-methyloctan-2-yl)phenyl)-7,7-dimethylbicyclo[2.2.1]hept-2-en-1-yl)methanol (HU-910) on liver injury induced by 1 h of ischaemia followed by 2, 6 or 24 h of reperfusion, using a well-established mouse model of segmental hepatic I/R. KEY RESULTS Displacement of [3H]CP55940 by HU-910 from specific binding sites in CHO cell membranes transfected with human CB2 or CB1 receptors (hCB1/2) yielded Ki values of 6 nM and 1.4 µM respectively. HU-910 inhibited forskolin-stimulated cyclic AMP production by hCB2 CHO cells (EC50= 162 nM) and yielded EC50 of 26.4 nM in [35S]GTPγS binding assays using hCB2 expressing CHO membranes. HU-910 given before ischaemia significantly attenuated levels of I/R-induced hepatic pro-inflammatory chemokines (CCL3 and CXCL2), TNF-α, inter-cellular adhesion molecule-1, neutrophil infiltration, oxidative stress and cell death. Some of the beneficial effect of HU-910 also persisted when given at the beginning of the reperfusion or 1 h after the ischaemic episode. Furthermore, HU-910 attenuated the bacterial endotoxin-triggered TNF-α production in isolated Kupffer cells and expression of adhesion molecules in primary human liver sinusoidal endothelial cells stimulated with TNF-α. Pretreatment with a CB2 receptor antagonist attenuated the protective effects of HU-910, while pretreatment with a CB1 antagonist tended to enhance them. CONCLUSION AND IMPLICATIONS HU-910 is a potent CB2 receptor agonist which may exert protective effects in various diseases associated with inflammation and tissue injury. LINKED ARTICLES This article is part of a themed section on Cannabinoids in Biology and Medicine. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2012.165.issue-8. To view Part I of Cannabinoids in Biology and Medicine visit http://dx.doi.org/10.1111/bph.2011.163.issue-7 PMID:21449982

SU-F-T-181: Proton Therapy Tissue-Equivalence of 3D Printed Materials

DOE Office of Scientific and Technical Information (OSTI.GOV)

Taylor, P; Craft, D; Followill, D

Purpose: This work investigated the proton tissue-equivalence of various 3D printed materials. Methods: Three 3D printers were used to create 5 cm cubic phantoms made of different plastics with varying percentages of infill. White resin, polylactic acid (PLA), and NinjaFlex plastics were used. The infills ranged from 15% to 100%. Each phantom was scanned with a CT scanner to obtain the HU value. The relative linear stopping power (RLSP) was then determined using a multi-layer ion chamber in a 200 MeV proton beam. The RLSP was measured both parallel and perpendicular to the print direction for each material. Results: Themore » HU values of the materials ranged from lung-equivalent (−820 HU σ160) when using a low infill, to soft-tissue-equivalent 159 (σ12). The RLSP of the materials depended on the orientation of the beam relative to the print direction. When the proton beam was parallel to the print direction, the RLSP was generally higher than the RLSP in the perpendicular orientation, by up to 45%. This difference was smaller (less than 6%) for the materials with 100% infill. For low infill cubes irradiated parallel to the print direction, the SOBP curve showed extreme degradation of the beam in the distal region. The materials with 15–25% infill had wide-ranging agreement with a clinical HU-RLSP conversion curve, with some measurements falling within 1% of the curve and others deviating up to 45%. The materials with 100% infill all fell within 7% of the curve. Conclusion: While some materials tested fall within 1% of a clinical HU-RLSP curve, caution should be taken when using 3D printed materials with proton therapy, as the orientation of the beam relative to the print direction can result in a large change in RLSP. Further investigation is needed to measure how the infill pattern affects the material RLSP. This work was supported by PHS grant CA180803.« less

Design of a multimodal (1H/23Na MR/CT) anthropomorphic thorax phantom.

PubMed

Neumann, Wiebke; Lietzmann, Florian; Schad, Lothar R; Zöllner, Frank G

2017-06-01

This work proposes a modular, anthropomorphic MR and CT thorax phantom that enables the comparison of experimental studies for quantitative evaluation of deformable, multimodal image registration algorithms and realistic multi-nuclear MR imaging techniques. A human thorax phantom was developed with insertable modules representing lung, liver, ribs and additional tracking spheres. The quality of human tissue mimicking characteristics was evaluated for 1 H and 23 Na MR as well as CT imaging. The position of landmarks in the lung lobes was tracked during CT image acquisition at several positions during breathing cycles. 1 H MR measurements of the liver were repeated after seven months to determine long term stability. The modules possess HU, T 1 and T 2 values comparable to human tissues (lung module: -756±148HU, artificial ribs: 218±56HU (low CaCO 3 concentration) and 339±121 (high CaCO 3 concentration), liver module: T 1 =790±28ms, T 2 =65±1ms). Motion analysis showed that the landmarks in the lung lobes follow a 3D trajectory similar to human breathing motion. The tracking spheres are well detectable in both CT and MRI. The parameters of the tracking spheres can be adjusted in the following ranges to result in a distinct signal: HU values from 150 to 900HU, T 1 relaxation time from 550ms to 2000ms, T 2 relaxation time from 40ms to 200ms. The presented anthropomorphic multimodal thorax phantom fulfills the demands of a simple, inexpensive system with interchangeable components. In future, the modular design allows for complementing the present set up with additional modules focusing on specific research targets such as perfusion studies, 23 Na MR quantification experiments and an increasing level of complexity for motion studies. Copyright © 2016. Published by Elsevier GmbH.

SU-F-J-114: On-Treatment Imagereconstruction Using Transit Images of Treatment Beams Through Patient and Thosethrough Planning CT Images

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lee, H; Cho, S; Cheong, K

Purpose: To reconstruct patient images at the time of radiation delivery using measured transit images of treatment beams through patient and calculated transit images through planning CT images. Methods: We hypothesize that the ratio of the measured transit images to the calculated images may provide changed amounts of the patient image between times of planning CT and treatment. To test, we have devised lung phantoms with a tumor object (3-cm diameter) placed at iso-center (simulating planning CT) and off-center by 1 cm (simulating treatment). CT images of the two phantoms were acquired; the image of the off-centered phantom, unavailable clinically,more » represents the reference on-treatment image in the image quality of planning CT. Cine-transit images through the two phantoms were also acquired in EPID from a non-modulated 6 MV beam when the gantry was rotated 360 degrees; the image through the centered phantom simulates calculated image. While the current study is a feasibility study, in reality our computational EPID model can be applicable in providing accurate transit image from MC simulation. Changed MV HU values were reconstructed from the ratio between two EPID projection data, converted to KV HU values, and added to the planning CT, thereby reconstructing the on-treatment image of the patient limited to the irradiated region of the phantom. Results: The reconstructed image was compared with the reference image. Except for local HU differences>200 as a maximum, excellent agreement was found. The average difference across the entire image was 16.2 HU. Conclusion: We have demonstrated the feasibility of a method of reconstructing on-treatment images of a patient using EPID image and planning CT images. Further studies will include resolving the local HU differences and investigation on the dosimetry impact of the reconstructed image.« less

High hydrostatic pressure inactivation of murine norovirus and human noroviruses on green onions and in salsa.

PubMed

Sido, Robert F; Huang, Runze; Liu, Chuhan; Chen, Haiqiang

2017-02-02

In this study, high hydrostatic pressure (HHP) was evaluated as an intervention for human noroviruses (HuNoVs) in green onions and salsa. To determine the effect of water during HHP treatment on virus inactivation, a HuNoV surrogate, murine norovirus 1 (MNV-1), was inoculated onto green onions and then HHP-treated at 350MPa with or without water at 4 or 20°C. The presence of water enhanced HHP inactivation of MNV-1 on green onions at 4°C but not at 20°C. To test the temperature effect on HHP inactivation of MNV-1, inoculated green onions were HHP-treated at 300MPa at 1, 4 and 10°C. As the temperature decreased, MNV-1 became more sensitive to HHP treatment. HHP inactivation curves of MNV-1 on green onions and salsa were obtained at 300 or 350MPa for 0.5-3min at 1°C. All three inactivation curves showed a linear relationship between log reduction of MNV-1 and time. D values of HHP inactivation of MNV-1 on green onions were 1.10 and 0.61min at 300 and 350MPa, respectively. The D value of HHP inactivation of MNV-1 in salsa at 300MPa was 0.63min. HHP inactivation of HuNoV GI.1 and GII.4 on green onions and salsa was also conducted. To achieve >3 log reduction of HuNoV GI.1, HHP treatments for 2min at 1°C should be conducted at 600MPa and 500MPa for green onions and salsa, respectively. To achieve >3 log reduction of HuNoV GII.4, HHP treatments for 2min at 1°C should be conducted at 500MPa and 300MPa for green onions and salsa, respectively. Copyright © 2016 Elsevier B.V. All rights reserved.

Choline deficiency causes reversible hepatic abnormalities in patients receiving parenteral nutrition: proof of a human choline requirement: a placebo-controlled trial.

PubMed

Buchman, A L; Ament, M E; Sohel, M; Dubin, M; Jenden, D J; Roch, M; Pownall, H; Farley, W; Awal, M; Ahn, C

2001-01-01

Previous studies have shown that plasma free choline concentrations are significantly decreased in many long-term home total parenteral nutrition (TPN) patients. Furthermore, low choline status has been associated with both hepatic morphologic and hepatic aminotransferase abnormalities. A preliminary pilot study suggested choline-supplemented TPN may be useful in reversal of these hepatic abnormalities. Fifteen patients (10 M, 5 F) who had required TPN for > or =80% of their nutritional needs were randomized to receive their usual TPN (n = 8), or TPN to which 2 g choline chloride had been added (n = 7) for 24 weeks. Baseline demographic data were similar between groups. Patients had CT scans of the liver and spleen, and blood for plasma free and phospholipid-bound choline, alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase, gamma glutamyl transferase (GGT), bilirubin, serum lipids, complete blood count (CBC), and chemistry profile obtained at baseline, and weeks 2, 4, 6, 12, 16, 20, 24, and 34. CT scans were analyzed for Hounsfield unit (HU) densities. There were no significant differences in any measured parameters after 2 weeks. However, at 4 weeks, a significant difference in liver HU between groups was observed (13.3+/-5.0 HU [choline] vs 5.8+/-5.2 HU [placebo], p = .04). This significant trend continued through week 24. Recurrent hepatic steatosis and decreased HU were observed at week 34, 10 weeks after choline supplementation had been discontinued. A significant increase in the liver-spleen differential HU was also observed in the choline group (10.6+/-6.2 HU [choline] vs 1.3+/-3.3 HU [placebo], p = .01). Serum ALT decreased significantly (p = .01 to .05) in the choline group vs placebo at weeks 6,12, 20, and 24. Serum AST was significantly decreased in the choline group by week 24 (p = .02). The serum alkaline phosphatase was significantly reduced in the choline group at weeks 2, 12, 20, 24, and 34 (p = .02 to 0.07). Total bilirubin was normal in these patients and remained unchanged during the study. Serum GGT tended to decrease more in the choline group, but the greater decrease was not statistically significant. Choline deficiency is a significant contributor to the development of TPN-associated liver disease. The data suggest choline is a required nutrient for long-term home TPN patients.

Shading correction for cone-beam CT in radiotherapy: validation of dose calculation accuracy using clinical images

NASA Astrophysics Data System (ADS)

Marchant, T. E.; Joshi, K. D.; Moore, C. J.

2017-03-01

Cone-beam CT (CBCT) images are routinely acquired to verify patient position in radiotherapy (RT), but are typically not calibrated in Hounsfield Units (HU) and feature non-uniformity due to X-ray scatter and detector persistence effects. This prevents direct use of CBCT for re-calculation of RT delivered dose. We previously developed a prior-image based correction method to restore HU values and improve uniformity of CBCT images. Here we validate the accuracy with which corrected CBCT can be used for dosimetric assessment of RT delivery, using CBCT images and RT plans for 45 patients including pelvis, lung and head sites. Dose distributions were calculated based on each patient's original RT plan and using CBCT image values for tissue heterogeneity correction. Clinically relevant dose metrics were calculated (e.g. median and minimum target dose, maximum organ at risk dose). Accuracy of CBCT based dose metrics was determined using an "override ratio" method where the ratio of the dose metric to that calculated on a bulk-density assigned version of the image is assumed to be constant for each patient, allowing comparison to "gold standard" CT. For pelvis and head images the proportion of dose errors >2% was reduced from 40% to 1.3% after applying shading correction. For lung images the proportion of dose errors >3% was reduced from 66% to 2.2%. Application of shading correction to CBCT images greatly improves their utility for dosimetric assessment of RT delivery, allowing high confidence that CBCT dose calculations are accurate within 2-3%.

Alternative role of HuD splicing variants in neuronal differentiation.

PubMed

Hayashi, Satoru; Yano, Masato; Igarashi, Mana; Okano, Hirotaka James; Okano, Hideyuki

2015-03-01

HuD is a neuronal RNA-binding protein that plays an important role in neuronal differentiation of the nervous system. HuD has been reported to have three RNA recognition motifs (RRMs) and three splice variants (SVs) that differ in their amino acid sequences between RRM2 and RRM3. This study investigates whether these SVs have specific roles in neuronal differentiation. In primary neural epithelial cells under differentiating conditions, HuD splice variant 1 (HuD-sv1), which is a general form, and HuD-sv2 were expressed at all tested times, whereas HuD-sv4 was transiently expressed at the beginning of differentiation, indicating that HuD-sv4 might play a role compared different from that of HuD-sv1. Indeed, HuD-sv4 did not promote neuronal differentiation in epithelial cells, whereas HuD-sv1 did promote neuronal differentiation. HuD-sv4 overexpression showed less neurite-inducing activity than HuD-sv1 in mouse neuroblastoma N1E-115 cells; however, HuD-sv4 showed stronger growth-arresting activity. HuD-sv1 was localized only in the cytoplasm, whereas HuD-sv4 was localized in both the cytoplasm and the nuclei. The Hu protein has been reported to be involved in translation and alternative splicing in the cytoplasm and nuclei, respectively. Consistent with this observation, HuD-sv1 showed translational activity on p21, which plays a role in growth arrest and neuronal differentiation, whereas HuD-sv4 did not. By contrast, HuD-sv4 showed stronger pre-mRNA splicing activity than did HuD-sv1 on Clasp2, which participates in cell division. Therefore, HuD SVs might play a role in controlling the timing of proliferation/differentiation switching by controlling the translation and alternative splicing of target genes. © 2014 Wiley Periodicals, Inc.

A study of the dependence of protocol optimization on the left ventricular ejection fraction (LVEF) in coronary CT angiography (CCTA) examination

NASA Astrophysics Data System (ADS)

Yu, Dong-Su; Cho, Jae-Hwan; Park, Cheol-Soo; Yoo, Heung-Joon; Choi, Cheon-Woong; Kim, Dae-Hyun

2013-10-01

The purpose of this study is to obtain a good quality image and to minimize patient doses and re-examination rates through an optimization of the protocol for coronary computed tomography angiography (CCTA) examination based on a comparison and an analysis of the heart rates (HRs) of patients who had left ventricular ejection fraction (LVEF) values of less than 40% and the HRs of ordinary patients. This study targeted 16 patients who received thallium single-photon emission computed tomography (SPECT) or echocardiography simultaneously among the patients who took the CCTA examinations. Depending on the LVEF value (30 ˜ 39, 40 ˜ 49, 50 ˜ 59, and 60% or above), the patients were divided into groups of four based on HR (50 ˜ 59, 60 ˜ 69, 70 ˜ 79, and 80 or above). DynEva software was used to set the region of interest (ROI) on the ascending aorta and for a measurement of the threshold value. Comparisons and analyses were made based on the LVEF values and the HRs, after which the results were compared with the ones from the existing examination protocols and contrast medium protocols. According to the study results, the relation between the HR and the LVEF demonstrated that it took a long time to reach the true 100 hounsfield unit (HU) when the LVEF was 40% or below. Contrasting media showed significant differences, except in the case where the HR was 80 or above, and/or the LVEF was less than 40%. Moreover, for an LVEF of less than 40%, time differences were significant when contrasting media reached the true 100 HU to begin the scanning process. Therefore, it was possible to predict that the contrasting media were already being washed out from the left ventricle.

Hu antigen R (HuR) multimerization contributes to glioma disease progression.

PubMed

Filippova, Natalia; Yang, Xiuhua; Ananthan, Subramaniam; Sorochinsky, Anastasia; Hackney, James R; Gentry, Zachery; Bae, Sejong; King, Peter; Nabors, L Burt

2017-10-13

Among primary brain cancers, gliomas are the most deadly and most refractory to current treatment modalities. Previous reports overwhelmingly support the role of the RNA-binding protein Hu antigen R (HuR) as a positive regulator of glioma disease progression. HuR expression is consistently elevated in tumor tissues, and a cytoplasmic localization appears essential for HuR-dependent oncogenic transformation. Here, we report HuR aggregation (multimerization) in glioma and the analysis of this tumor-specific HuR protein multimerization in clinical brain tumor samples. Using a split luciferase assay, a bioluminescence resonance energy transfer technique, and site-directed mutagenesis, we examined the domains involved in HuR multimerization. Results obtained with the combination of the split HuR luciferase assay with the bioluminescence resonance energy transfer technique suggested that multiple (at least three) HuR molecules come together during HuR multimerization in glioma cells. Using these data, we developed a model of HuR multimerization in glioma cells. We also demonstrate that exposing glioma cells to the HuR inhibitor tanshinone group compound 15,16-dihydrotanshinone-I or to the newly identified compound 5 disrupts HuR multimerization modules and reduces tumor cell survival and proliferation. In summary, our findings provide new insights into HuR multimerization in glioma and highlight possible pharmacological approaches for targeting HuR domains involved in cancer cell-specific multimerization.

Structure-based Analysis to Hu-DNA Binding

DOE Office of Scientific and Technical Information (OSTI.GOV)

Swinger,K.; Rice, P.

2007-01-01

HU and IHF are prokaryotic proteins that induce very large bends in DNA. They are present in high concentrations in the bacterial nucleoid and aid in chromosomal compaction. They also function as regulatory cofactors in many processes, such as site-specific recombination and the initiation of replication and transcription. HU and IHF have become paradigms for understanding DNA bending and indirect readout of sequence. While IHF shows significant sequence specificity, HU binds preferentially to certain damaged or distorted DNAs. However, none of the structurally diverse HU substrates previously studied in vitro is identical with the distorted substrates in the recently publishedmore » Anabaena HU(AHU)-DNA cocrystal structures. Here, we report binding affinities for AHU and the DNA in the cocrystal structures. The binding free energies for formation of these AHU-DNA complexes range from 10-14.5 kcal/mol, representing K{sub d} values in the nanomolar to low picomolar range, and a maximum stabilization of at least 6.3 kcal/mol relative to complexes with undistorted, non-specific DNA. We investigated IHF binding and found that appropriate structural distortions can greatly enhance its affinity. On the basis of the coupling of structural and relevant binding data, we estimate the amount of conformational strain in an IHF-mediated DNA kink that is relieved by a nick (at least 0.76 kcal/mol) and pinpoint the location of the strain. We show that AHU has a sequence preference for an A+T-rich region in the center of its DNA-binding site, correlating with an unusually narrow minor groove. This is similar to sequence preferences shown by the eukaryotic nucleosome.« less

Influence of technical parameters on epicardial fat volume quantification at cardiac CT.

PubMed

Bucher, Andreas M; Joseph Schoepf, U; Krazinski, Aleksander W; Silverman, Justin; Spearman, James V; De Cecco, Carlo N; Meinel, Felix G; Vogl, Thomas J; Geyer, Lucas L

2015-06-01

To systematically analyze the influence of technical parameters on quantification of epicardial fat volume (EATV) at cardiac CT. 153 routine cardiac CT data sets were analyzed using three-dimensional pericardial border delineation. Three image series were reconstructed per patient: (a) CTAD: coronary CT angiography (CTA), diastolic phase; (b) CTAS: coronary CTA, systolic phase; (c) CaScD: non-contrast CT, diastolic phase. EATV was calculated using three different upper thresholds (-15HU, -30 HU, -45HU). Repeated measures ANOVA, Spearman's rho, and Bland Altman plots were used. Mean EATV differed between all three image series at a -30HU threshold (CTAD 87.2 ± 38.5 ml, CTAS 90.9 ± 37.7 ml, CaScD 130.7 ± 49.5 ml, P<0.001). EATV of diastolic and systolic CTA reconstructions did not differ significantly (P=0.225). Mean EATV for contrast enhanced CTA at a -15HU threshold (CTAD15 102.4 ± 43.6 ml, CTAS15 105.3 ± 42.3 ml) could be approximated most closely by non-contrast CT at -45HU threshold (CaScD45 105.3 ± 40.8 ml). The correlation was excellent: CTAS15-CTAD15, rho=0.943; CTAD15-CaScD45, rho=0.905; CTAS15-CaScD45, rho=0.924; each P<0.001). Bias values from Bland Altman Analysis were: CTAS15-CTAD15, 4.9%; CTAD15-CaScD45, -4.3%; CTAS15-CaScD45, 0.6%. Measured EATV can differ substantially between contrast enhanced and non-contrast CT studies, which can be reconciled by threshold modification. Heart cycle phase does not significantly influence EATV measurements. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

High Resolution Diffusion Tensor Imaging of Cortical-Subcortical White Matter Tracts in TBI

DTIC Science & Technology

2009-10-01

other words, CT perfusion is a change in CT intensity (or Hounsfield Unit , HU) over time following a bolus of iodine based contrast agent. Although...E-Mail: little@uic.edu 5f. WORK UNIT NUMBER 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) 8. PERFORMING ORGANIZATION REPORT...estimates of the eigenvalues and decrease the signal-to-noise ratio, a background noise level of 125 (MR Units ) was applied prior to calculation of

SU-F-J-210: A Preliminary Study On the Dosimetric Impact of Detector Based Spectral Ct On Proton Therapy Treatment Planning

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cheng, C; Lee, S; Wessels, B

2016-06-15

Purpose: To compare the difference in Hounsfield unit-relative stopping power and evaluate the dosimetric impact of spectral vs. conventional CT on proton therapy treatment plans. Method: The Philips prototype (IQon), a detector-based, spectral CT system (spectral) was used to scan calibration and Rando phantoms. Data were reconstructed with and without energy decomposition to produce monoenergetic 70 keV, 140 keV, and the Zeff images. Relative stopping power (RSP) in the head and lung regions were evaluated as a function of HU in order to compare spectral and conventional CT. Treatment plans for the Rando phantom were also generated and used tomore » produce DVHs of fictitious target volume and organ-at-risk contoured on the head and lung. Results: Agreement of the Zeff of the tissue-substitute materials determined using spectral CT agrees to within 1 to 5% of the Zeff of the known phantom composition. The discrepancy is primarily attributed to non-uniformity in the phantom. Differences between the HU-RSP curves obtained using spectral and conventional CT were small except for in the lung curve at HU>1000. The large difference in planned doses using Spectral vs. conventional CT occurred in a low-dose brain region (1.7mm between the locations of the 100 cGy lines and 3 mm for 50 cGy lines). Conclusion: Conventionally, a single HU-RSP from CT scanner is used in proton treatment planning. Spectral CT allows site-specific HU-RSP for each patient. Spectral and conventional HU-RSP may result in different distributions as shown here. Additional study is required to evaluate the impact of Spectral CT in proton treatment planning. This study is part of a research agreement between Philips and University Hospitals/Case Medical Center.« less

SU-E-I-63: Quantitative Evaluation of the Effects of Orthopedic Metal Artifact Reduction (OMAR) Software On CT Images for Radiotherapy Simulation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jani, S

Purpose: CT simulation for patients with metal implants can often be challenging due to artifacts that obscure tumor/target delineation and normal organ definition. Our objective was to evaluate the effectiveness of Orthopedic Metal Artifact Reduction (OMAR), a commercially available software, in reducing metal-induced artifacts and its effect on computed dose during treatment planning. Methods: CT images of water surrounding metallic cylindrical rods made of aluminum, copper and iron were studied in terms of Hounsfield Units (HU) spread. Metal-induced artifacts were characterized in terms of HU/Volume Histogram (HVH) using the Pinnacle treatment planning system. Effects of OMAR on enhancing our abilitymore » to delineate organs on CT and subsequent dose computation were examined in nine (9) patients with hip implants and two (2) patients with breast tissue expanders. Results: Our study characterized water at 1000 HU with a standard deviation (SD) of about 20 HU. The HVHs allowed us to evaluate how the presence of metal changed the HU spread. For example, introducing a 2.54 cm diameter copper rod in water increased the SD in HU of the surrounding water from 20 to 209, representing an increase in artifacts. Subsequent use of OMAR brought the SD down to 78. Aluminum produced least artifacts whereas Iron showed largest amount of artifacts. In general, an increase in kVp and mA during CT scanning showed better effectiveness of OMAR in reducing artifacts. Our dose analysis showed that some isodose contours shifted by several mm with OMAR but infrequently and were nonsignificant in planning process. Computed volumes of various dose levels showed <2% change. Conclusions: In our experience, OMAR software greatly reduced the metal-induced CT artifacts for the majority of patients with implants, thereby improving our ability to delineate tumor and surrounding organs. OMAR had a clinically negligible effect on computed dose within tissues. Partially funded by unrestricted educational grant from Philips.« less

Correlation between clot density and recanalization success or stroke etiology in acute ischemic stroke patients

PubMed Central

Kallmes, David F; Brinjikji, Waleed

2017-01-01

Background Predicting recanalization success for patients undergoing endovascular treatment for acute ischemic stroke is of significant interest. Studies have previously correlated the success of recanalization with the density of the clot. We evaluated clot density and its relationship to revascularization success and stroke etiology. Methods We conducted a retrospective review of 118 patients undergoing intra-arterial therapy for acute ischemic stroke. Mean and maximum thrombus density was measured by drawing a circular region of interest on an axial slice of a non-contrast computed tomography scan. T-tests were used to compare clot density to recanalization success or to stroke etiology, namely large artery atherosclerosis and cardioembolism. Recanalization success was compared in four device groups: aspiration, stent retriever, aspiration and stent retriever, and all other. Results There was no significant difference in the mean clot density in patients with successful (n = 80) versus unsuccessful recanalization (n = 38, 50.1 ± 7.4 Hounsfield unit (HU) vs. 53 ± 12.7 HU; P = 0.17). Comparing the large artery thromboembolism (n = 35) to the cardioembolic etiology group (n = 56), there was no significant difference in mean clot density (51.5 ± 7.7 HU vs. 49.7 ± 8.5 HU; P = 0.31). A subgroup analysis of middle cerebral artery occlusions (n = 65) showed similar, non-statistically significant differences between groups. There was no difference in the rate of recanalization success in patients with a mean clot density greater than 50 HU or less than 50 HU in each of the four device groups. Conclusions There was no relationship between clot density and revascularization success or stroke etiology in our study. More research is needed to determine if clot density can predict recanalization rates or indicate etiology. PMID:28604188

Impact of tube current modulation on lesion conspicuity index in hi-resolution chest computed tomography

NASA Astrophysics Data System (ADS)

Szczepura, Katy; Tomkinson, David; Manning, David

2017-03-01

Tube current modulation is a method employed in the use of CT in an attempt to optimize radiation dose to the patient. The acceptable noise (noise index) can be varied, based on the level of optimization required; higher accepted noise reduces the patient dose. Recent research [1] suggests that measuring the conspicuity index (C.I.) of focal lesions within an image is more reflective of a clinical reader's ability to perceive focal lesions than traditional physical measures such as contrast to noise (CNR) and signal to noise ratio (SNR). Software has been developed and validated to calculate the C.I. in DICOM images. The aim of this work is assess the impact of tube current modulation on conspicuity index and CTDIvol, to indicate the benefits and limitations of tube current modulation on lesion detectability. Method An anthropomorphic chest phantom was used "Lungman" with inserted lesions of varying size and HU (see table below) a range of Hounsfield units and sizes were used to represent the variation in lesion Hounsfield units found. This meant some lesions had negative Hounsfield unit values.

"X-Map 2.0" for Edema Signal Enhancement for Acute Ischemic Stroke Using Non-Contrast-Enhanced Dual-Energy Computed Tomography.

PubMed

Taguchi, Katsuyuki; Itoh, Toshihide; Fuld, Matthew K; Fournie, Eric; Lee, Okkyun; Noguchi, Kyo

2018-03-14

A novel imaging technique ("X-map") has been developed to identify acute ischemic lesions for stroke patients using non-contrast-enhanced dual-energy computed tomography (NE-DE-CT). Using the 3-material decomposition technique, the original X-map ("X-map 1.0") eliminates fat and bone from the images, suppresses the gray matter (GM)-white matter (WM) tissue contrast, and makes signals of edema induced by severe ischemia easier to detect. The aim of this study was to address the following 2 problems with the X-map 1.0: (1) biases in CT numbers (or artifacts) near the skull of NE-DE-CT images and (2) large intrapatient and interpatient variations in X-map 1.0 values. We improved both an iterative beam-hardening correction (iBHC) method and the X-map algorithm. The new iBHC (iBHC2) modeled x-ray physics more accurately. The new X-map ("X-map 2.0") estimated regional GM values-thus, maximizing the ability to suppress the GM-WM contrast, make edema signals quantitative, and enhance the edema signals that denote an increased water density for each pixel. We performed a retrospective study of 11 patients (3 men, 8 women; mean age, 76.3 years; range, 68-90 years) who presented to the emergency department with symptoms of acute stroke. Images were reconstructed with the old iBHC (iBHC1) and the iBHC2, and biases in CT numbers near the skull were measured. Both X-map 2.0 maps and X-map 1.0 maps were computed from iBHC2 images, both with and without a material decomposition-based edema signal enhancement (ESE) process. X-map values were measured at 5 to 9 locations on GM without infarct per patient; the mean value was calculated for each patient (we call it the patient-mean X-map value) and subtracted from the measured X-map values to generate zero-mean X-map values. The standard deviation of the patient-mean X-map values over multiple patients denotes the interpatient variation; the standard deviation over multiple zero-mean X-map values denotes the intrapatient variation. The Levene F test was performed to assess the difference in the standard deviations with different algorithms. Using 5 patient data who had diffusion weighted imaging (DWI) within 2 hours of NE-DE-CT, mean values at and near ischemic lesions were measured at 7 to 14 locations per patient with X-map images, CT images (low kV and high kV), and DWI images. The Pearson correlation coefficient was calculated between a normalized increase in DWI signals and either X-map or CT. The bias in CT numbers was lower with iBHC2 than with iBHC1 in both high- and low-kV images (2.5 ± 2.0 HU [95% confidence interval (CI), 1.3-3.8 HU] for iBHC2 vs 6.9 ± 2.3 HU [95% CI, 5.4-8.3 HU] for iBHC1 with high-kV images, P < 0.01; 1.5 ± 3.6 HU [95% CI, -0.8 to 3.7 HU] vs 12.8 ± 3.3 HU [95% CI, 10.7-14.8 HU] with low-kV images, P < 0.01). The interpatient variation was smaller with X-map 2.0 than with X-map 1.0, both with and without ESE (4.3 [95% CI, 3.0-7.6] for X-map 2.0 vs 19.0 [95% CI, 13.3-22.4] for X-map 1.0, both with ESE, P < 0.01; 3.0 [95% CI, 2.1-5.3] vs 12.0 [95% CI, 8.4-21.0] without ESE, P < 0.01). The intrapatient variation was also smaller with X-map 2.0 than with X-map 1.0 (6.2 [95% CI, 5.3-7.3] vs 8.5 [95% CI, 7.3-10.1] with ESE, P = 0.0122; 4.1 [95% CI, 3.6-4.9] vs 6.3 [95% CI, 5.5-7.6] without ESE, P < 0.01). The best 3 correlation coefficients (R) with DWI signals were -0.733 (95% CI, -0.845 to -0.560, P < 0.001) for X-map 2.0 with ESE, -0.642 (95% CI, -0.787 to -0.429, P < 0.001) for high-kV CT, and -0.609 (95% CI, -0.766 to -0.384, P < 0.001) for X-map 1.0 with ESE. Both of the 2 problems outlined in the objectives have been addressed by improving both iBHC and X-map algorithm. The iBHC2 improved the bias in CT numbers and the visibility of GM-WM contrast throughout the brain space. The combination of iBHC2 and X-map 2.0 with ESE decreased both intrapatient and interpatient variations of edema signals significantly and had a strong correlation with DWI signals in terms of the strength of edema signals.

Domain-specific phosphomimetic mutation allows dissection of different protein kinase C (PKC) isotype-triggered activities of the RNA binding protein HuR.

PubMed

Schulz, Sebastian; Doller, Anke; Pendini, Nicole R; Wilce, Jacqueline A; Pfeilschifter, Josef; Eberhardt, Wolfgang

2013-12-01

The ubiquitous mRNA binding protein human antigen R (HuR) participates in the post-transcriptional regulation of many AU-rich element (ARE)-bearing mRNAs. Previously, by using in vitro kinase assay, we have identified serines (Ser) 158, 221 and 318 as targets of protein kinase C (PKC)-triggered phosphorylation. In this study, we tested whether GFP- or GST-tagged HuR constructs bearing a phosphomimetic Ser (S)-to-Asp (D) substitution at the different PKC target sites, would affect different HuR functions including HuR nucleo-cytoplasmic redistribution and binding to different types of ARE-containing mRNAs. The phosphomimetic GFP-tagged HuR protein bearing a phosphomimetic substitution in the hinge region of HuR (HuR-S221D) showed an increased cytoplasmic abundance when compared to wild-type HuR. Conversely, data from in vitro kinase assay and electrophoretic mobility shift assay (EMSA), implicates that phosphorylation at Ser 221 is not relevant for mRNA binding of HuR. Quantification of in vitro binding affinities of GST-tagged wild-type HuR and corresponding HuR proteins bearing a phosphomimetic substitution in either RRM2 (HuR-S158D) or in RRM3 (HuR-S318D) by microscale thermophoresis (MST) indicates a specific binding of wild-type HuR to type I, II or type III-ARE-oligonucleotides in the high nanomolar range. Interestingly, phosphomimetic mutation at position 158 or 318 had a negative influence on HuR binding to type I- and type II-ARE-mRNAs whereas it significantly enhanced HuR affinity to a type III-ARE substrate. Our data suggest that differential phosphorylation of HuR by PKCs at different HuR domains coordinates subcellular HuR distribution and leads to a preferential binding to U-rich bearing target mRNA. © 2013.

Prospective ECG-Triggered Coronary CT Angiography: Clinical Value of Noise-Based Tube Current Reduction Method with Iterative Reconstruction

PubMed Central

Shen, Junlin; Du, Xiangying; Guo, Daode; Cao, Lizhen; Gao, Yan; Yang, Qi; Li, Pengyu; Liu, Jiabin; Li, Kuncheng

2013-01-01

Objectives To evaluate the clinical value of noise-based tube current reduction method with iterative reconstruction for obtaining consistent image quality with dose optimization in prospective electrocardiogram (ECG)-triggered coronary CT angiography (CCTA). Materials and Methods We performed a prospective randomized study evaluating 338 patients undergoing CCTA with prospective ECG-triggering. Patients were randomly assigned to fixed tube current with filtered back projection (Group 1, n = 113), noise-based tube current with filtered back projection (Group 2, n = 109) or with iterative reconstruction (Group 3, n = 116). Tube voltage was fixed at 120 kV. Qualitative image quality was rated on a 5-point scale (1 = impaired, to 5 = excellent, with 3–5 defined as diagnostic). Image noise and signal intensity were measured; signal-to-noise ratio was calculated; radiation dose parameters were recorded. Statistical analyses included one-way analysis of variance, chi-square test, Kruskal-Wallis test and multivariable linear regression. Results Image noise was maintained at the target value of 35HU with small interquartile range for Group 2 (35.00–35.03HU) and Group 3 (34.99–35.02HU), while from 28.73 to 37.87HU for Group 1. All images in the three groups were acceptable for diagnosis. A relative 20% and 51% reduction in effective dose for Group 2 (2.9 mSv) and Group 3 (1.8 mSv) were achieved compared with Group 1 (3.7 mSv). After adjustment for scan characteristics, iterative reconstruction was associated with 26% reduction in effective dose. Conclusion Noise-based tube current reduction method with iterative reconstruction maintains image noise precisely at the desired level and achieves consistent image quality. Meanwhile, effective dose can be reduced by more than 50%. PMID:23741444

TH-C-BRD-06: A Novel MRI Based CT Artifact Correction Method for Improving Proton Range Calculation in the Presence of Severe CT Artifacts

DOE Office of Scientific and Technical Information (OSTI.GOV)

Park, P; Schreibmann, E; Fox, T

2014-06-15

Purpose: Severe CT artifacts can impair our ability to accurately calculate proton range thereby resulting in a clinically unacceptable treatment plan. In this work, we investigated a novel CT artifact correction method based on a coregistered MRI and investigated its ability to estimate CT HU and proton range in the presence of severe CT artifacts. Methods: The proposed method corrects corrupted CT data using a coregistered MRI to guide the mapping of CT values from a nearby artifact-free region. First patient MRI and CT images were registered using 3D deformable image registration software based on B-spline and mutual information. Themore » CT slice with severe artifacts was selected as well as a nearby slice free of artifacts (e.g. 1cm away from the artifact). The two sets of paired MRI and CT images at different slice locations were further registered by applying 2D deformable image registration. Based on the artifact free paired MRI and CT images, a comprehensive geospatial analysis was performed to predict the correct CT HU of the CT image with severe artifact. For a proof of concept, a known artifact was introduced that changed the ground truth CT HU value up to 30% and up to 5cm error in proton range. The ability of the proposed method to recover the ground truth was quantified using a selected head and neck case. Results: A significant improvement in image quality was observed visually. Our proof of concept study showed that 90% of area that had 30% errors in CT HU was corrected to 3% of its ground truth value. Furthermore, the maximum proton range error up to 5cm was reduced to 4mm error. Conclusion: MRI based CT artifact correction method can improve CT image quality and proton range calculation for patients with severe CT artifacts.« less

Pervious Concrete with Titanium Dioxide as a Photocatalyst Compound for a Greener Road Environment

DOT National Transportation Integrated Search

2012-11-11

With the rapid development in transportation related activities and the growth of population density in urban and metropolitan area, the United States is now facing significant challenges in controlling air pollution and the associated problems in hu...

The effects of low levels of herbicides on simple plant communities

EPA Science Inventory

In the United States, the US Environmental Protection Agency has the responsibility for the registration of pesticides under the Federal Insecticide, Fungicide, and Rodenticide Act. Prior to registration applicants must demonstrate that their product will not adversely affect hu...

The Potential Biomarkers to Identify the Development of Steatosis in Hyperuricemia

PubMed Central

He, Xiaojuan; Lu, Cheng; He, Bing; Niu, Xuyan; Xiao, Cheng; Xu, Gang; Bian, Zhaoxiang; Zu, Xianpeng; Zhang, Ge; Zhang, Weidong; Lu, Aiping

2016-01-01

Hyperuricemia (HU) often progresses to combine with non-alcoholic fatty liver disease (NAFLD) in the clinical scenario, which further exacerbates metabolic disorders; early detection of biomarkers, if obtained during the HU progression, may be beneficial for preventing its combination with NAFLD. This study aimed to decipher the biomarkers and mechanisms of the development of steatosis in HU. Four groups of subjects undergoing health screening, including healthy subjects, subjects with HU, subjects with HU combined with NAFLD (HU+NAFLD) and subjects with HU initially and then with HU+NAFLD one year later (HU→HU+NAFLD), were recruited in this study. The metabolic profiles of all subjects’ serum were analyzed by liquid chromatography quadruple time-of-flight mass spectrometry. The metabolomic data from subjects with HU and HU+NAFLD were compared, and the biomarkers for the progression from HU to HU+NAFLD were predicted. The metabolomic data from HU→HU+NAFLD subjects were collected for further verification. The results showed that the progression was associated with disturbances of phospholipase metabolism, purine nucleotide degradation and Liver X receptor/retinoic X receptor activation as characterized by up-regulated phosphatidic acid, cholesterol ester (18:0) and down-regulated inosine. These metabolic alterations may be at least partially responsible for the development of steatosis in HU. This study provides a new paradigm for better understanding and further prevention of disease progression. PMID:26890003

[Distribution characteristics of soil humus fractions stable carbon isotope natural abundance (delta 13C) in paddy field under long-term ridge culture].

PubMed

Tang, Xiao-hong; Luo, You-jin; Ren, Zhen-jiang; Lü, Jia-ke; Wei, Chao-fu

2011-04-01

A 16-year field experiment was conducted in a ridge culture paddy field in the hilly region of Sichuan Basin, aimed to investigate the distribution characteristics of stable carbon isotope natural abundance (delta 13C) in soil humus fractions. The soil organic carbon (SOC) content in the paddy field under different cultivation modes ranked in the order of wide ridge culture > ridge culture > paddy and upland rotation. In soil humus substances (HS), humin (HU) was the main composition, occupying 21% - 30% of the total SOC. In the extracted soil carbon, humic acid (HA) dominated, occupying 17% - 21% of SOC and 38% - 65% of HS. The delta 13C value of SOC ranged from -27.9 per thousand to -25.6 per thousand, and the difference of the delta 13C value between 0-5 cm and 20-40 cm soil layers was about 1.9 per thousand. The delta 13C value of HA under different cultivation modes was 1 per thousand - 2 per thousand lower than that of SOC, and more approached to the delta 13C value of rapeseed and rice residues. As for fulvic acid (FA), its delta 13C value was about 2 per thousand and 4 per thousand higher than that of SOC and HA, respectively. The delta 13C value of HU in plough layer (0-20 cm) and plow layer (20-40 cm) ranged from -23.7 per thousand - -24.9 per thousand and -22.6 per thousand - -24.2 per thousand, respectively, reflecting the admixture of young and old HS. The delta 13C value in various organic carbon fractions was HU>FA>SOC>rapeseed and rice residues>HA. Long-term rice planting benefited the increase of SOC content, and cultivation mode played an important role in affecting the distribution patterns of soil humus delta 13C in plough layer and plow layer.

CRISPR Knockout of the HuR Gene Causes a Xenograft Lethal Phenotype

PubMed Central

Lal, Shruti; Cheung, Edwin C.; Zarei, Mahsa; Preet, Ranjan; Chand, Saswati N.; Mambelli-Lisboa, Nicole C.; Romeo, Carmella; Stout, Matthew C.; Londin, Eric; Goetz, Austin; Lowder, Cinthya Y.; Nevler, Avinoam; Yeo, Charles J.; Campbell, Paul M.; Winter, Jordan M.; Dixon, Dan A.; Brody, Jonathan R.

2017-01-01

Pancreatic ductal adenocarcinoma (PDA) is the third leading cause of cancer related deaths in the U.S., while colorectal cancer (CRC) is the third most common cancer. The RNA binding protein HuR (ELAVL1), supports a pro-oncogenic network in gastrointestinal (GI) cancer cells through enhanced HuR expression. Using a publically available database, HuR expression levels were determined to be increased in primary PDA and CRC tumor cohorts as compared to normal pancreas and colon tissues, respectively. CRISPR/Cas9 technology was successfully used to delete the HuR gene in both PDA (MIA PaCa-2 and Hs 766T) and CRC (HCT116) cell lines. HuR deficiency has a mild phenotype, in vitro, as HuR-deficient MIA PaCa-2 (MIA.HuR-KO(−/−)) cells had increased apoptosis when compared to isogenic wild-type (MIA.HuR-WT(+/+)) cells. Using this isogenic system, mRNAs were identified that specifically bound to HuR and were required for transforming a 2D culture into 3D (i.e., organoids). Importantly, HuR-deficient MIA PaCa-2 and Hs 766T cells were unable to engraft tumors in vivo compared to control HuR-proficient cells, demonstrating a unique xenograft lethal phenotype. While not as a dramatic phenotype, CRISPR knockout HuR HCT116 colon cancer cells (HCT.HuR-KO(−/−)) showed significantly reduced in vivo tumor growth compared to controls (HCT.HuR-WT(+/+)). Finally, HuR deletion affects KRAS activity and controls a subset of pro-oncogenic genes. Implications The work reported here supports the notion that targeting HuR is a promising therapeutic strategy to treat GI malignancies. PMID:28242812

A new cannabinoid CB2 receptor agonist HU-910 attenuates oxidative stress, inflammation and cell death associated with hepatic ischaemia/reperfusion injury.

PubMed

Horváth, Bėla; Magid, Lital; Mukhopadhyay, Partha; Bátkai, Sándor; Rajesh, Mohanraj; Park, Ogyi; Tanchian, Galin; Gao, Rachel Y; Goodfellow, Catherine E; Glass, Michelle; Mechoulam, Raphael; Pacher, Pál

2012-04-01

Cannabinoid CB(2) receptor activation has been reported to attenuate myocardial, cerebral and hepatic ischaemia-reperfusion (I/R) injury. We have investigated the effects of a novel CB(2) receptor agonist ((1S,4R)-2-(2,6-dimethoxy-4-(2-methyloctan-2-yl)phenyl)-7,7-dimethylbicyclo[2.2.1]hept-2-en-1-yl)methanol (HU-910) on liver injury induced by 1 h of ischaemia followed by 2, 6 or 24 h of reperfusion, using a well-established mouse model of segmental hepatic I/R. Displacement of [(3) H]CP55940 by HU-910 from specific binding sites in CHO cell membranes transfected with human CB(2) or CB(1) receptors (hCB(1/2) ) yielded K(i) values of 6 nM and 1.4 µM respectively. HU-910 inhibited forskolin-stimulated cyclic AMP production by hCB(2) CHO cells (EC(50) = 162 nM) and yielded EC(50) of 26.4 nM in [(35) S]GTPγS binding assays using hCB(2) expressing CHO membranes. HU-910 given before ischaemia significantly attenuated levels of I/R-induced hepatic pro-inflammatory chemokines (CCL3 and CXCL2), TNF-α, inter-cellular adhesion molecule-1, neutrophil infiltration, oxidative stress and cell death. Some of the beneficial effect of HU-910 also persisted when given at the beginning of the reperfusion or 1 h after the ischaemic episode. Furthermore, HU-910 attenuated the bacterial endotoxin-triggered TNF-α production in isolated Kupffer cells and expression of adhesion molecules in primary human liver sinusoidal endothelial cells stimulated with TNF-α. Pretreatment with a CB(2) receptor antagonist attenuated the protective effects of HU-910, while pretreatment with a CB(1) antagonist tended to enhance them. HU-910 is a potent CB(2) receptor agonist which may exert protective effects in various diseases associated with inflammation and tissue injury. This article is part of a themed section on Cannabinoids in Biology and Medicine. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2012.165.issue-8. To view Part I of Cannabinoids in Biology and Medicine visit http://dx.doi.org/10.1111/bph.2011.163.issue-7. Published 2011. This article is a U.S. Government work and is in the public domain in the USA.

Differentiation of low-attenuation intracranial hemorrhage and calcification using dual-energy computed tomography in a phantom system

PubMed Central

Nute, Jessica L.; Roux, Lucia Le; Chandler, Adam G.; Baladandayuthapani, Veera; Schellingerhout, Dawid; Cody, Dianna D.

2015-01-01

Objectives Calcific and hemorrhagic intracranial lesions with attenuation levels of <100 Hounsfield Units (HU) cannot currently be reliably differentiated by single-energy computed tomography (SECT). The proper differentiation of these lesion types would have a multitude of clinical applications. A phantom model was used to test the ability of dual-energy CT (DECT) to differentiate such lesions. Materials and Methods Agar gel-bound ferric oxide and hydroxyapatite were used to model hemorrhage and calcification, respectively. Gel models were scanned using SECT and DECT and organized into SECT attenuation-matched pairs at 16 attenuation levels between 0 and 100 HU. DECT data were analyzed using 3D Gaussian mixture models (GMMs), as well as a simplified threshold plane metric derived from the 3D GMM, to assign voxels to hemorrhagic or calcific categories. Accuracy was calculated by comparing predicted voxel assignments with actual voxel identities. Results We measured 6,032 voxels from each gel model, for a total of 193,024 data points (16 matched model pairs). Both the 3D GMM and its more clinically implementable threshold plane derivative yielded similar results, with >90% accuracy at matched SECT attenuation levels ≥50 HU. Conclusions Hemorrhagic and calcific lesions with attenuation levels between 50 and 100 HU were differentiable using DECT in a clinically relevant phantom system with >90% accuracy. This method warrants further testing for potential clinical applications. PMID:25162534

Losartan alleviates hyperuricemia-induced atherosclerosis in a rabbit model.

PubMed

Zheng, Hongchao; Li, Ning; Ding, Yueyou; Miao, Peizhi

2015-01-01

To investigate the mechanisms underlying the therapeutic effects of losartan on hyperuricemia-induced aortic atherosclerosis, in an experimental rabbit model. Male rabbits (n = 48) were divided into control, hyperuricemia (HU), hypercholesterolemia + hyperuricemia (HC + HU) and high-purine with 30-mg/kg/d losartan (HU + losartan) groups. Serum uric acid (UA) and plasma renin and angiotensin II activities were determined. Aortic tissue specimens were analyzed for histological changes and proliferating cell nuclear antigen (PCNA). Liver tissues were sampled for quantitative analyses of liver low-density lipoprotein receptor (LDLR) mRNA and protein via reverse transcription polymerase chain reaction and western blotting. After 12 weeks, serum UA and plasma renin and plasma angiotensin II activities were enhanced in the HU and HU + HC groups (P < 0.001) compared to the control, whereas in the HU + losartan group plasma renin activity was not different and serum UA concentrations as well as plasma angiotensin II activity were moderately enhanced (P < 0.05). Smooth muscle cell (SMC) PCNA expression increased strongly in the HU and HU + HC groups (P < 0.001), but was less pronounced in the HU + losartan group. In contrast, transcription and expression of LDLR mRNA and protein were significantly higher in the control and HU + losartan groups compared to the HU and HU + HC groups. Both the HU and HU + HC groups had elevated intima thickness and intima areas compared to the control and HU + losartan groups. Losartan can alleviate experimental atherosclerosis induced by hyperuricemia.

Losartan alleviates hyperuricemia-induced atherosclerosis in a rabbit model

PubMed Central

Zheng, Hongchao; Li, Ning; Ding, Yueyou; Miao, Peizhi

2015-01-01

Objective: To investigate the mechanisms underlying the therapeutic effects of losartan on hyperuricemia-induced aortic atherosclerosis, in an experimental rabbit model. Methods: Male rabbits (n = 48) were divided into control, hyperuricemia (HU), hypercholesterolemia + hyperuricemia (HC + HU) and high-purine with 30-mg/kg/d losartan (HU + losartan) groups. Serum uric acid (UA) and plasma renin and angiotensin II activities were determined. Aortic tissue specimens were analyzed for histological changes and proliferating cell nuclear antigen (PCNA). Liver tissues were sampled for quantitative analyses of liver low-density lipoprotein receptor (LDLR) mRNA and protein via reverse transcription polymerase chain reaction and western blotting. Results: After 12 weeks, serum UA and plasma renin and plasma angiotensin II activities were enhanced in the HU and HU + HC groups (P < 0.001) compared to the control, whereas in the HU + losartan group plasma renin activity was not different and serum UA concentrations as well as plasma angiotensin II activity were moderately enhanced (P < 0.05). Smooth muscle cell (SMC) PCNA expression increased strongly in the HU and HU + HC groups (P < 0.001), but was less pronounced in the HU + losartan group. In contrast, transcription and expression of LDLR mRNA and protein were significantly higher in the control and HU + losartan groups compared to the HU and HU + HC groups. Both the HU and HU + HC groups had elevated intima thickness and intima areas compared to the control and HU + losartan groups. Conclusions: Losartan can alleviate experimental atherosclerosis induced by hyperuricemia. PMID:26617751

The cytoskeletal inhibitors latrunculin A and blebbistatin exert antitumorigenic properties in human hepatocellular carcinoma cells by interfering with intracellular HuR trafficking

DOE Office of Scientific and Technical Information (OSTI.GOV)

Doller, Anke; Badawi, Amel; Schmid, Tobias

The impact of the RNA-binding protein HuR for the post-transcriptional deregulation of tumor-relevant genes is well established. Despite of elevations in HuR expression levels, an increase in cytoplasmic HuR abundance in many cases correlates with a high grade of malignancy. Here, we demonstrated that administration of the actin-depolymerizing macrolide latrunculin A, or blebbistatin, an inhibitor of myosin II ATPase activity, caused a dose- and time-dependent reduction in the high cytoplasmic HuR content of HepG2 and Huh7 hepatocellular carcinoma (HCC) cells. Subcellular fractionation revealed that in addition, both inhibitors strongly attenuated cytoskeletal and membrane-bound HuR abundance and conversely increased the HuRmore » amount in nuclear cell fractions. Concomitant with changes in intracellular HuR localization, both cytoskeletal inhibitors markedly decreased the half-lives of cyclooxygenase-2 (COX-2), cyclin A and cyclin D{sub 1} encoding mRNAs resulting in a significant reduction in their expression levels in HepG2 cells. Importantly, a similar reduction in the expression of these HuR targets was achieved by a RNA interference (RNAi)-mediated knockdown of either HuR or nonmuscle myoin IIA. Using polysomal fractionation, we further demonstrate that the decrease in cytoplasmic HuR by latrunculin A or blebbistatin is accompanied by a marked change in the allocation of HuR and its mRNA cargo from polysomes to ribonucleoprotein (RNP) particles. Functionally, the basal migration and prostaglandin E{sub 2} synthesis are similarly impaired in inhibitor-treated and stable HuR-knockdown HepG2 cells. Our data demonstrate that interfering with the actomyosin-dependent HuR trafficking may comprise a valid therapeutic option for antagonizing pathologic posttranscriptional gene expression by HuR and furthermore emphasize the potential benefit of HuR inhibitory strategies for treatment of HCC. - Highlights: • We tested the effects of latrunculin A and blebbistatin on different HuR activities. • Both cytoskeletal inhibitors disturbed the RNP-polysome HuR allocation in HepG2 cells. • Accordingly, both inhibitors reduced the stability and levels of HuR controlled mRNAs. • Functionally, important HuR-triggered cell functions were impaired by both compounds. • Targeting of HuR trafficking implies a useful approach for novel antitumor therapy.« less

Optimal Cotton Insecticide Application Termination Timing: A Meta-Analysis.

PubMed

Griffin, T W; Zapata, S D

2016-08-01

The concept of insecticide termination timing is generally accepted among cotton (Gossypium hirsutum) researchers; however, exact timings are often disputed. Specifically, there is uncertainty regarding the last economic insecticide application to control fruit-feeding pests including tarnished plant bug (Lygus lineolaris (Palisot de Beauvois)), boll weevil (Anthonomus grandis), bollworm (Helicoverpa zea), tobacco budworm (Heliothis virescens), and cotton fleahopper (Pseudatomoscelis seriatus). A systematic review of prior studies was conducted within a meta-analytic framework. Nine publicly available articles were amalgamated to develop an optimal timing principle. These prior studies reported 53 independent multiple means comparison field experiments for a total of 247 trial observations. Stochastic plateau theory integrated with econometric meta-analysis methodology was applied to the meta-database to determine the shape of the functional form of both the agronomic optimal insecticide termination timing and corresponding yield potential. Results indicated that current university insecticide termination timing recommendations are later than overall estimated timing suggested. The estimated 159 heat units (HU) after the fifth position above white flower (NAWF5) was found to be statistically different than the 194 HU termination used as the status quo recommended termination timing. Insecticides applied after 159 HU may have been applied in excess, resulting in unnecessary economic and environmental costs. Empirical results also suggested that extending the insecticide termination time by one unit resulted in a cotton lint yield increase of 0.27 kilograms per hectare up to the timing where the plateau began. Based on economic analyses, profit-maximizing producers may cease application as soon as 124 HU after NAWF5. These results provided insights useful to improve production systems by applying inputs only when benefits were expected to be in excess of the respective costs. © The Authors 2016. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

The characterization of small hypoattenuating renal masses on contrast-enhanced CT☆

PubMed Central

Patel, Neesha S.; Poder, Liina; Wang, Zhen J.; Yeh, Benjamin M.; Qayyum, Aliya; Jin, Hua; Coakley, Fergus V.

2011-01-01

Purpose To determine if small hypoattenuating renal masses can be characterized as simple cysts or renal cell carcinomas on contrast-enhanced computed tomography (CT). Materials and methods We retrospectively identified 20 small (≤1.5 cm) hypoattenuating renal masses seen on contrast enhanced CT, consisting of 14 simple cysts and six renal cell carcinomas. Three independent readers recorded subjective visual impression (five-point scale from 1=definitely fluid to 5=definitely solid), CT attenuation, border (well circumscribed or ill defined), and shape (ovoid or irregular) for each lesion. Results The overall area under the receiver operator characteristic curves for subjective visual impression, CT attenuation, border, and shape were 0.97, 0.82, 0.59, and 0.55, respectively. Using dichotomized ratings (1–2=cyst and 3–5=carcinoma), subjective impression had a sensitivity and specificity of 100% and 79–100%, respectively, for the diagnosis of renal cell carcinoma. Using a threshold of 50 Hounsfield Units (HU) or more, CT attenuation had a sensitivity and specificity of 100% and 43–64%, respectively. Conclusion Small hypoattenuating renal masses can be characterized with reasonable accuracy by subjective impression and CT attenuation; lesions that appear solid on visual inspection or have an attenuation value of 50 HU or more are likely to be renal cell carcinoma. © 2009 Elsevier Inc. All rights reserved. PMID:19559352

Energy-Specific Optimization of Attenuation Thresholds for Low-Energy Virtual Monoenergetic Images in Renal Lesion Evaluation.

PubMed

Patel, Bhavik N; Farjat, Alfredo; Schabel, Christoph; Duvnjak, Petar; Mileto, Achille; Ramirez-Giraldo, Juan Carlos; Marin, Daniele

2018-05-01

The purpose of this study was to determine in vitro and in vivo the optimal threshold for renal lesion vascularity at low-energy (40-60 keV) virtual monoenergetic imaging. A rod simulating unenhanced renal parenchymal attenuation (35 HU) was fitted with a syringe containing water. Three iodinated solutions (0.38, 0.57, and 0.76 mg I/mL) were inserted into another rod that simulated enhanced renal parenchyma (180 HU). Rods were inserted into cylindric phantoms of three different body sizes and scanned with single- and dual-energy MDCT. In addition, 102 patients (32 men, 70 women; mean age, 66.8 ± 12.9 [SD] years) with 112 renal lesions (67 nonvascular, 45 vascular) measuring 1.1-8.9 cm underwent single-energy unenhanced and contrast-enhanced dual-energy CT. Optimal threshold attenuation values that differentiated vascular from nonvascular lesions at 40-60 keV were determined. Mean optimal threshold values were 30.2 ± 3.6 (standard error), 20.9 ± 1.3, and 16.1 ± 1.0 HU in the phantom, and 35.9 ± 3.6, 25.4 ± 1.8, and 17.8 ± 1.8 HU in the patients at 40, 50, and 60 keV. Sensitivity and specificity for the thresholds did not change significantly between low-energy and 70-keV virtual monoenergetic imaging (sensitivity, 87-98%; specificity, 90-91%). The AUC from 40 to 70 keV was 0.96 (95% CI, 0.93-0.99) to 0.98 (95% CI, 0.95-1.00). Low-energy virtual monoenergetic imaging at energy-specific optimized attenuation thresholds can be used for reliable characterization of renal lesions.

TU-G-BRA-02: Can We Extract Lung Function Directly From 4D-CT Without Deformable Image Registration?

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kipritidis, J; Woodruff, H; Counter, W

Purpose: Dynamic CT ventilation imaging (CT-VI) visualizes air volume changes in the lung by evaluating breathing-induced lung motion using deformable image registration (DIR). Dynamic CT-VI could enable functionally adaptive lung cancer radiation therapy, but its sensitivity to DIR parameters poses challenges for validation. We hypothesize that a direct metric using CT parameters derived from Hounsfield units (HU) alone can provide similar ventilation images without DIR. We compare the accuracy of Direct and Dynamic CT-VIs versus positron emission tomography (PET) images of inhaled {sup 68}Ga-labelled nanoparticles (‘Galligas’). Methods: 25 patients with lung cancer underwent Galligas 4D-PET/CT scans prior to radiation therapy.more » For each patient we produced three CT- VIs. (i) Our novel method, Direct CT-VI, models blood-gas exchange as the product of air and tissue density at each lung voxel based on time-averaged 4D-CT HU values. Dynamic CT-VIs were produced by evaluating: (ii) regional HU changes, and (iii) regional volume changes between the exhale and inhale 4D-CT phase images using a validated B-spline DIR method. We assessed the accuracy of each CT-VI by computing the voxel-wise Spearman correlation with free-breathing Galligas PET, and also performed a visual analysis. Results: Surprisingly, Direct CT-VIs exhibited better global correlation with Galligas PET than either of the dynamic CT-VIs. The (mean ± SD) correlations were (0.55 ± 0.16), (0.41 ± 0.22) and (0.29 ± 0.27) for Direct, Dynamic HU-based and Dynamic volume-based CT-VIs respectively. Visual comparison of Direct CT-VI to PET demonstrated similarity for emphysema defects and ventral-to-dorsal gradients, but inability to identify decreased ventilation distal to tumor-obstruction. Conclusion: Our data supports the hypothesis that Direct CT-VIs are as accurate as Dynamic CT-VIs in terms of global correlation with Galligas PET. Visual analysis, however, demonstrated that different CT-VI algorithms might have varying accuracy depending on the underlying cause of ventilation abnormality. This research was supported by a National Health and Medical Research Council (NHMRC) Australia Fellowship, an Cancer Institute New South Wales Early Career Fellowship 13-ECF-1/15 and NHMRC scholarship APP1038399. No commercial funding was received for this work.« less

A model-based scatter artifacts correction for cone beam CT

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhao, Wei; Zhu, Jun; Wang, Luyao

2016-04-15

Purpose: Due to the increased axial coverage of multislice computed tomography (CT) and the introduction of flat detectors, the size of x-ray illumination fields has grown dramatically, causing an increase in scatter radiation. For CT imaging, scatter is a significant issue that introduces shading artifact, streaks, as well as reduced contrast and Hounsfield Units (HU) accuracy. The purpose of this work is to provide a fast and accurate scatter artifacts correction algorithm for cone beam CT (CBCT) imaging. Methods: The method starts with an estimation of coarse scatter profiles for a set of CBCT data in either image domain ormore » projection domain. A denoising algorithm designed specifically for Poisson signals is then applied to derive the final scatter distribution. Qualitative and quantitative evaluations using thorax and abdomen phantoms with Monte Carlo (MC) simulations, experimental Catphan phantom data, and in vivo human data acquired for a clinical image guided radiation therapy were performed. Scatter correction in both projection domain and image domain was conducted and the influences of segmentation method, mismatched attenuation coefficients, and spectrum model as well as parameter selection were also investigated. Results: Results show that the proposed algorithm can significantly reduce scatter artifacts and recover the correct HU in either projection domain or image domain. For the MC thorax phantom study, four-components segmentation yields the best results, while the results of three-components segmentation are still acceptable. The parameters (iteration number K and weight β) affect the accuracy of the scatter correction and the results get improved as K and β increase. It was found that variations in attenuation coefficient accuracies only slightly impact the performance of the proposed processing. For the Catphan phantom data, the mean value over all pixels in the residual image is reduced from −21.8 to −0.2 HU and 0.7 HU for projection domain and image domain, respectively. The contrast of the in vivo human images is greatly improved after correction. Conclusions: The software-based technique has a number of advantages, such as high computational efficiency and accuracy, and the capability of performing scatter correction without modifying the clinical workflow (i.e., no extra scan/measurement data are needed) or modifying the imaging hardware. When implemented practically, this should improve the accuracy of CBCT image quantitation and significantly impact CBCT-based interventional procedures and adaptive radiation therapy.« less

Technical Note: Multipurpose CT, ultrasound, and MRI breast phantom for use in radiotherapy and minimally invasive interventions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ruschin, Mark, E-mail: Mark.Ruschin@sunnybrook.ca; Chin, Lee; Ravi, Ananth

Purpose: To develop a multipurpose gel-based breast phantom consisting of a simulated tumor with realistic imaging properties in CT, ultrasound and MRI, or a postsurgical cavity on CT. Applications for the phantom include: deformable image registration (DIR) quality assurance (QA), autosegmentation validation, and localization testing and training for minimally invasive image-guided procedures such as those involving catheter or needle insertion. Methods: A thermoplastic mask of a typical breast patient lying supine was generated and then filled to make an array of phantoms. The background simulated breast tissue consisted of 32.4 g each of ballistic gelatin (BG) powder and Metamusil™ (MM)more » dissolved in 800 ml of water. Simulated tumors were added using the following recipe: 12 g of barium sulfate (1.4% v/v) plus 0.000 14 g copper sulfate plus 0.7 g of MM plus 7.2 g of BG all dissolved in 75 ml of water. The phantom was evaluated quantitatively in CT by comparing Hounsfield units (HUs) with actual breast tissue. For ultrasound and MRI, the phantoms were assessed based on subjective image quality and signal-difference to noise (SDNR) ratio, respectively. The stiffness of the phantom was evaluated based on ultrasound elastography measurements to yield an average Young’s modulus. In addition, subjective tactile assessment of phantom was performed under needle insertion. Results: The simulated breast tissue had a mean background value of 24 HU on CT imaging, which more closely resembles fibroglandular tissue (40 HU) as opposed to adipose (−100 HU). The tumor had a mean CT number of 45 HU, which yielded a qualitatively realistic image contrast relative to the background either as an intact tumor or postsurgical cavity. The tumor appeared qualitatively realistic on ultrasound images, exhibiting hypoechoic characteristics compared to background. On MRI, the tumor exhibited a SDNR of 3.7. The average Young’s modulus was computed to be 15.8 ± 0.7 kPa (1 SD). Conclusions: We have developed a process to efficiently and inexpensively produce multipurpose breast phantoms containing simulated tumors visible on CT, ultrasound, and MRI. The phantoms have been evaluated for image quality and elasticity and can serve as a medium for DIR QA, autosegmentation QA, and training for minimally invasive procedures.« less

A pilot study using low-dose Spectral CT and ASIR (Adaptive Statistical Iterative Reconstruction) algorithm to diagnose solitary pulmonary nodules.

PubMed

Xiao, Huijuan; Liu, Yihe; Tan, Hongna; Liang, Pan; Wang, Bo; Su, Lei; Wang, Suya; Gao, Jianbo

2015-11-17

Lung cancer is the most common cancer which has the highest mortality rate. With the development of computed tomography (CT) techniques, the case detection rates of solitary pulmonary nodules (SPN) has constantly increased and the diagnosis accuracy of SPN has remained a hot topic in clinical and imaging diagnosis. The aim of this study was to evaluate the combination of low-dose spectral CT and ASIR (Adaptive Statistical Iterative Reconstruction) algorithm in the diagnosis of solitary pulmonary nodules (SPN). 62 patients with SPN (42 cases of benign SPN and 20 cases of malignant SPN, pathology confirmed) were scanned by spectral CT with a dual-phase contrast-enhanced method. The iodine and water concentration (IC and WC) of the lesion and the artery in the image that had the same density were measured by the GSI (Gemstone Spectral Imaging) software. The normalized iodine and water concentration (NIC and NWC) of the lesion and the normalized iodine and water concentration difference (ICD and WCD) between the arterial and venous phases (AP and VP) were also calculated. The spectral HU (Hounsfield Unit ) curve was divided into 3 sections based on the energy (40-70, 70-100 and 100-140 keV) and the slopes (λHU) in both phases were calculated. The ICAP, ICVP, WCAP and WCVP, NIC and NWC, and the λHU in benign and malignant SPN were compared by independent sample t-test. The iodine related parameters (ICAP, ICVP, NICAP, NICVP, and the ICD) of malignant SPN were significantly higher than that of benign SPN (t = 3.310, 1.330, 2.388, 1.669 and 3.251, respectively, P <0.05). The 3 λHU values of venous phase in malignant SPN were higher than that of benign SPN (t = 3.803, 2.846 and 3.205, P <0.05). The difference of water related parameters (WCAP, WCVP, NWCAP, NWCVP and WCD) between malignant and benign SPN were not significant (t = 0.666, 0.257, 0.104, 0.550 and 0.585, P > 0.05). The iodine related parameters and the slope of spectral curve are useful markers to distinguish the benign from the malignant lung diseases, and its application is extremely feasible in clinical applications.

Hindlimb unloading induces a collagen isoform shift in the soleus muscle of the rat.

PubMed

Miller, T A; Lesniewski, L A; Muller-Delp, J M; Majors, A K; Scalise, D; Delp, M D

2001-11-01

To determine whether hindlimb unloading (HU) alters the extracellular matrix of skeletal muscle, male Sprague-Dawley rats were subjected to 0 (n = 11), 1 (n = 11), 14 (n = 13), or 28 (n = 11) days of unloading. Remodeling of the soleus and plantaris muscles was examined biochemically for collagen abundance via measurement of hydroxyproline, and the percentage of cross-sectional area of collagen was determined histologically with picrosirius red staining. Total hydroxyproline content in the soleus and plantaris muscles was unaltered by HU at any time point. However, the relative proportions of type I collagen in the soleus muscle decreased relative to control (Con) with 14 and 28 days HU (Con 68 +/- 5%; 14 days HU 53 +/- 4%; 28 days HU 53 +/- 7%). Correspondingly, type III collagen increased in soleus muscle with 14 and 28 days HU (Con 32 +/- 5%; 14 days HU 47 +/- 4%; 28 days HU 48 +/- 7%). The proportion of type I muscle fibers in soleus muscle was diminished with HU (Con 96 +/- 2%; 14 days HU 86 +/- 1%; 28 days HU 83 +/- 1%), and the proportion of hybrid type I/IIB fibers increased (Con 0%; 14 days HU 8 +/- 2%; 28 days HU 14 +/- 2%). HU had no effect on the proportion of type I and III collagen or muscle fiber composition in plantaris muscle. The data demonstrate that HU induces a shift in the relative proportion of collagen isoform (type I to III) in the antigravity soleus muscle, which occurs concomitantly with a slow-to-fast myofiber transformation.

Hindlimb unloading induces a collagen isoform shift in the soleus muscle of the rat

NASA Technical Reports Server (NTRS)

Miller, T. A.; Lesniewski, L. A.; Muller-Delp, J. M.; Majors, A. K.; Scalise, D.; Delp, M. D.

2001-01-01

To determine whether hindlimb unloading (HU) alters the extracellular matrix of skeletal muscle, male Sprague-Dawley rats were subjected to 0 (n = 11), 1 (n = 11), 14 (n = 13), or 28 (n = 11) days of unloading. Remodeling of the soleus and plantaris muscles was examined biochemically for collagen abundance via measurement of hydroxyproline, and the percentage of cross-sectional area of collagen was determined histologically with picrosirius red staining. Total hydroxyproline content in the soleus and plantaris muscles was unaltered by HU at any time point. However, the relative proportions of type I collagen in the soleus muscle decreased relative to control (Con) with 14 and 28 days HU (Con 68 +/- 5%; 14 days HU 53 +/- 4%; 28 days HU 53 +/- 7%). Correspondingly, type III collagen increased in soleus muscle with 14 and 28 days HU (Con 32 +/- 5%; 14 days HU 47 +/- 4%; 28 days HU 48 +/- 7%). The proportion of type I muscle fibers in soleus muscle was diminished with HU (Con 96 +/- 2%; 14 days HU 86 +/- 1%; 28 days HU 83 +/- 1%), and the proportion of hybrid type I/IIB fibers increased (Con 0%; 14 days HU 8 +/- 2%; 28 days HU 14 +/- 2%). HU had no effect on the proportion of type I and III collagen or muscle fiber composition in plantaris muscle. The data demonstrate that HU induces a shift in the relative proportion of collagen isoform (type I to III) in the antigravity soleus muscle, which occurs concomitantly with a slow-to-fast myofiber transformation.

Dephosphorylation of HuR Protein during Alphavirus Infection Is Associated with HuR Relocalization to the Cytoplasm*

PubMed Central

Dickson, Alexa M.; Anderson, John R.; Barnhart, Michael D.; Sokoloski, Kevin J.; Oko, Lauren; Opyrchal, Mateusz; Galanis, Evanthia; Wilusz, Carol J.; Morrison, Thomas E.; Wilusz, Jeffrey

2012-01-01

We have demonstrated previously that the cellular HuR protein binds U-rich elements in the 3′ untranslated region (UTR) of Sindbis virus RNA and relocalizes from the nucleus to the cytoplasm upon Sindbis virus infection in 293T cells. In this study, we show that two alphaviruses, Ross River virus and Chikungunya virus, lack the conserved high-affinity U-rich HuR binding element in their 3′ UTRs but still maintain the ability to interact with HuR with nanomolar affinities through alternative binding elements. The relocalization of HuR protein occurs during Sindbis infection of multiple mammalian cell types as well as during infections with three other alphaviruses. Interestingly, the relocalization of HuR is not a general cellular reaction to viral infection, as HuR protein remained largely nuclear during infections with dengue and measles virus. Relocalization of HuR in a Sindbis infection required viral gene expression, was independent of the presence of a high-affinity U-rich HuR binding site in the 3′ UTR of the virus, and was associated with an alteration in the phosphorylation state of HuR. Sindbis virus-induced HuR relocalization was mechanistically distinct from the movement of HuR observed during a cellular stress response, as there was no accumulation of caspase-mediated HuR cleavage products. Collectively, these data indicate that virus-induced HuR relocalization to the cytoplasm is specific to alphavirus infections and is associated with distinct posttranslational modifications of this RNA-binding protein. PMID:22915590

A stoichiometric calibration method for dual energy computed tomography

NASA Astrophysics Data System (ADS)

Bourque, Alexandra E.; Carrier, Jean-François; Bouchard, Hugo

2014-04-01

The accuracy of radiotherapy dose calculation relies crucially on patient composition data. The computed tomography (CT) calibration methods based on the stoichiometric calibration of Schneider et al (1996 Phys. Med. Biol. 41 111-24) are the most reliable to determine electron density (ED) with commercial single energy CT scanners. Along with the recent developments in dual energy CT (DECT) commercial scanners, several methods were published to determine ED and the effective atomic number (EAN) for polyenergetic beams without the need for CT calibration curves. This paper intends to show that with a rigorous definition of the EAN, the stoichiometric calibration method can be successfully adapted to DECT with significant accuracy improvements with respect to the literature without the need for spectrum measurements or empirical beam hardening corrections. Using a theoretical framework of ICRP human tissue compositions and the XCOM photon cross sections database, the revised stoichiometric calibration method yields Hounsfield unit (HU) predictions within less than ±1.3 HU of the theoretical HU calculated from XCOM data averaged over the spectra used (e.g., 80 kVp, 100 kVp, 140 kVp and 140/Sn kVp). A fit of mean excitation energy (I-value) data as a function of EAN is provided in order to determine the ion stopping power of human tissues from ED-EAN measurements. Analysis of the calibration phantom measurements with the Siemens SOMATOM Definition Flash dual source CT scanner shows that the present formalism yields mean absolute errors of (0.3 ± 0.4)% and (1.6 ± 2.0)% on ED and EAN, respectively. For ion therapy, the mean absolute errors for calibrated I-values and proton stopping powers (216 MeV) are (4.1 ± 2.7)% and (0.5 ± 0.4)%, respectively. In all clinical situations studied, the uncertainties in ion ranges in water for therapeutic energies are found to be less than 1.3 mm, 0.7 mm and 0.5 mm for protons, helium and carbon ions respectively, using a generic reconstruction algorithm (filtered back projection). With a more advanced method (sinogram affirmed iterative technique), the values become 1.0 mm, 0.5 mm and 0.4 mm for protons, helium and carbon ions, respectively. These results allow one to conclude that the present adaptation of the stoichiometric calibration yields a highly accurate method for characterizing tissue with DECT for ion beam therapy and potentially for photon beam therapy.

Comparison of epicardial adipose tissue radiodensity threshold between contrast and non-contrast enhanced computed tomography scans: A cohort study of derivation and validation.

PubMed

Xu, Lingyu; Xu, Yuancheng; Coulden, Richard; Sonnex, Emer; Hrybouski, Stanislau; Paterson, Ian; Butler, Craig

2018-05-11

Epicardial adipose tissue (EAT) volume derived from contrast enhanced (CE) computed tomography (CT) scans is not well validated. We aim to establish a reliable threshold to accurately quantify EAT volume from CE datasets. We analyzed EAT volume on paired non-contrast (NC) and CE datasets from 25 patients to derive appropriate Hounsfield (HU) cutpoints to equalize two EAT volume estimates. The gold standard threshold (-190HU, -30HU) was used to assess EAT volume on NC datasets. For CE datasets, EAT volumes were estimated using three previously reported thresholds: (-190HU, -30HU), (-190HU, -15HU), (-175HU, -15HU) and were analyzed by a semi-automated 3D Fat analysis software. Subsequently, we applied a threshold correction to (-190HU, -30HU) based on mean differences in radiodensity between NC and CE images (ΔEATrd = CE radiodensity - NC radiodensity). We then validated our findings on EAT threshold in 21 additional patients with paired CT datasets. EAT volume from CE datasets using previously published thresholds consistently underestimated EAT volume from NC dataset standard by a magnitude of 8.2%-19.1%. Using our corrected threshold (-190HU, -3HU) in CE datasets yielded statistically identical EAT volume to NC EAT volume in the validation cohort (186.1 ± 80.3 vs. 185.5 ± 80.1 cm 3 , Δ = 0.6 cm 3 , 0.3%, p = 0.374). Estimating EAT volume from contrast enhanced CT scans using a corrected threshold of -190HU, -3HU provided excellent agreement with EAT volume from non-contrast CT scans using a standard threshold of -190HU, -30HU. Copyright © 2018. Published by Elsevier B.V.

Targeting Mycobacterium tuberculosis nucleoid-associated protein HU with structure-based inhibitors

NASA Astrophysics Data System (ADS)

Bhowmick, Tuhin; Ghosh, Soumitra; Dixit, Karuna; Ganesan, Varsha; Ramagopal, Udupi A.; Dey, Debayan; Sarma, Siddhartha P.; Ramakumar, Suryanarayanarao; Nagaraja, Valakunja

2014-06-01

The nucleoid-associated protein HU plays an important role in maintenance of chromosomal architecture and in global regulation of DNA transactions in bacteria. Although HU is essential for growth in Mycobacterium tuberculosis (Mtb), there have been no reported attempts to perturb HU function with small molecules. Here we report the crystal structure of the N-terminal domain of HU from Mtb. We identify a core region within the HU-DNA interface that can be targeted using stilbene derivatives. These small molecules specifically inhibit HU-DNA binding, disrupt nucleoid architecture and reduce Mtb growth. The stilbene inhibitors induce gene expression changes in Mtb that resemble those induced by HU deficiency. Our results indicate that HU is a potential target for the development of therapies against tuberculosis.

MO-FG-BRA-04: A Novel Time Weighted Density Correction for Stereotactic Lung Radiotherapy: A Phantom Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mohatt, D; Malhotra, H

Purpose: Conventional treatment plans for lung radiotherapy are created using either the free breathing (FB) scheme which represents the tumor at an arbitrary breathing phase of the patient’s respiratory cycle, or the average computed tomography (ACT) intensity projection over 10-binned phases. Neither method is entirely accurate because of the absence of time dependence of tumor movement. In the present “Hybrid” method, the HU of tumor in 3D space is determined by relative weighting of the HU of the tumor and lung in proportion to the time they spend at that location during the entire breathing cycle. Methods: A Quasar respiratorymore » motion phantom was employed to simulate lung tumor movement. Utilizing 4DCT image scans, volumetric modulated arc therapy (VMAT) plans were generated for three treatment planning scenarios which included conventional FB and ACT schemes, along with a third alternative Hybrid approach. Our internal target volume (ITV) hybrid structure was created using Boolean operation in Eclipse (ver. 11) treatment planning system, where independent sub-regions created by the gross tumor volume (GTV) overlap from the 10 motion phases were each assigned a time weighted CT value. The dose-volume-histograms (DVH) for each scheme were compared and analyzed. Results: Using our hybrid technique, we have demonstrated a reduction of 1.9% – 3.4% in total monitor units with respect to conventional treatment planning strategies, along with a 6 fold improvement in high dose spillage over the FB plan. The higher density ACT and Hybrid schemes also produced a slight enhancement in target conformity and reduction in low dose spillage. Conclusion: All treatment plans created in this study exceeded RTOG protocol criteria. Our results determine the free breathing approach yields an inaccurate account of the target treatment density. A significant decrease in unnecessary lung irradiation can be achieved by implementing Hybrid HU method with ACT method second best.« less

SU-E-J-268: Change of CT Number During the Course of Chemoradiation Therapy for Pancreatic Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, X; Dalah, E; Liu, F

2015-06-15

Purpose: It has been observed radiation can induce changes in CT number (CTN) inside tumor during the course of radiation therapy (RT) for several tumor sites including lung and head and neck, suggesting that the CTN change may be potentially used to assess RT response. In this study, we investigate the CTN changes inside tumor during the course of chemoradiation therapy (CRT) for pancreatic cancer. Methods: Daily diagnostic-quality CT data acquired during IGRT for 17 pancreatic head cancer patients using an in-room CT (CTVision, Siemens) were analyzed. All patients were treated with a radiation dose of 50.4 in 1.8 Gymore » per fraction. On each daily CT set, The contour of the pancreatic head, included in the treatment target, was generated by populating the pancreatic head contour from the planning CT or MRI using an auto-segmentation tool based on deformable registration (ABAS, Elekta) with manual editing if necessary. The CTN at each voxel in the pancreatic head contour was extracted and the 3D distribution of the CTNs was processed using MATLAB. The mean value of CTN distribution was used to quantify the daily CTN change in the pancreatic head. Results: Reduction of CTN in pancreatic head was observed during the CRT delivery in 14 out the 17 (82%) patients studied. Although the average reduction is only 3.5 Houncefield Unit (HU), this change is significant (p<0.01). Among them, there are 7 patients who had a CTN drop larger than 5 HU, ranging from 6.0 to 11.8 HU. In contrast to this trend, CTN was increased in 3 patients. Conclusion: Measurable changes in the CT number in tumor target were observed during the course of chemoradiation therapy for the pancreas cancer patients, indicating this radiation-induced CTN change may be used to assess treatment response.« less

Investigation of four-dimensional computed tomography-based pulmonary ventilation imaging in patients with emphysematous lung regions

NASA Astrophysics Data System (ADS)

Yamamoto, Tokihiro; Kabus, Sven; Klinder, Tobias; Lorenz, Cristian; von Berg, Jens; Blaffert, Thomas; Loo, Billy W., Jr.; Keall, Paul J.

2011-04-01

A pulmonary ventilation imaging technique based on four-dimensional (4D) computed tomography (CT) has advantages over existing techniques. However, physiologically accurate 4D-CT ventilation imaging has not been achieved in patients. The purpose of this study was to evaluate 4D-CT ventilation imaging by correlating ventilation with emphysema. Emphysematous lung regions are less ventilated and can be used as surrogates for low ventilation. We tested the hypothesis: 4D-CT ventilation in emphysematous lung regions is significantly lower than in non-emphysematous regions. Four-dimensional CT ventilation images were created for 12 patients with emphysematous lung regions as observed on CT, using a total of four combinations of two deformable image registration (DIR) algorithms: surface-based (DIRsur) and volumetric (DIRvol), and two metrics: Hounsfield unit (HU) change (VHU) and Jacobian determinant of deformation (VJac), yielding four ventilation image sets per patient. Emphysematous lung regions were detected by density masking. We tested our hypothesis using the one-tailed t-test. Visually, different DIR algorithms and metrics yielded spatially variant 4D-CT ventilation images. The mean ventilation values in emphysematous lung regions were consistently lower than in non-emphysematous regions for all the combinations of DIR algorithms and metrics. VHU resulted in statistically significant differences for both DIRsur (0.14 ± 0.14 versus 0.29 ± 0.16, p = 0.01) and DIRvol (0.13 ± 0.13 versus 0.27 ± 0.15, p < 0.01). However, VJac resulted in non-significant differences for both DIRsur (0.15 ± 0.07 versus 0.17 ± 0.08, p = 0.20) and DIRvol (0.17 ± 0.08 versus 0.19 ± 0.09, p = 0.30). This study demonstrated the strong correlation between the HU-based 4D-CT ventilation and emphysema, which indicates the potential for HU-based 4D-CT ventilation imaging to achieve high physiologic accuracy. A further study is needed to confirm these results.

Do clinical outcomes correlate with bone density after open reduction and internal fixation of tibial plateau fractures.

PubMed

Gausden, Elizabeth; Garner, Matthew R; Fabricant, Peter D; Warner, Stephen J; Shaffer, Andre D; Lorich, Dean G

2017-06-01

The operative management of tibial plateau fractures in elderly patients has historically led to inconsistent results, and these clinical outcomes were thought to be associated with poor bone quality often in elderly patients. The goal of this study was to investigate the relationship between bone density and subjective clinical outcome scores after open reduction and internal fixation of tibial plateau fractures. This is a retrospective cohort study from a single-surgeon conducted at an Academic, Level 1 Trauma Center. A preoperative computed tomography (CT) scan was obtained for all patients. Bone density of the distal femur was quantified with Hounsfield units (HU) as measured on axial CT scans. Inter-rater reliability of HU measurements was assessed using interclass correlation coefficients. Regression models controlling for age were used to identify relationships between bone density (HU) and the following variables: articular subsidence and 1-year subjective clinical outcomes scores [Knee Outcome Survey Activities of Daily Living Scale (KOS-ADLS), and Short-Form-36 (SF-36) physical and mental component scores (PCS, MCS)]. Sixty-one patients with a mean age of 59.3 years (range 27-85 years) and a minimum of 12 months of clinical follow-up were included in the study. The majority of the fractures (32 of 61) were classified as Schatzker II tibial plateau fractures, and there were 13 Schatzker V fractures, 11 Schatzker VI fractures, 2 Schatzker IV fractures and 1 Schatzker 1 fracture. HU measurements demonstrated an almost perfect inter-observer reliability (ICC = 0.97). Age was negatively correlated with HU measurements (r = -0.51, p < 0.001), and using a geriatric cut-off of 65 years of age, the geriatric group had a lower mean HU compared to the non-geriatric group (78.2 versus 114.8, p = 0.018). There was no significant relationship between bone quality, as assessed by distal femoral HU, and any subjective clinical outcome score. Inferior bone mineral density alone does not appear to affect clinical outcomes 1 year postoperatively when bone grafting is used to restore osseous voids. Poor bone quality should not be used as an indication for non-operative management of tibial plateau fractures.

TU-CD-BRA-08: Single-Energy Computed Tomography-Based Pulmonary Perfusion Imaging: Proof-Of-Principle in a Canine Model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yamamoto, T; Boone, J; Kent, M

Purpose: Pulmonary perfusion imaging has provided significant insights into pulmonary diseases, and can be useful in radiotherapy. The purpose of this study was to prospectively establish proof-of-principle in a canine model for single-energy CT-based perfusion imaging, which has the potential for widespread clinical implementation. Methods: Single-energy CT perfusion imaging is based on: (1) acquisition of inspiratory breath-hold CT scans before and after intravenous injection of iodinated contrast medium, (2) deformable image registration (DIR) of the two CT image data sets, and (3) subtraction of the pre-contrast image from post-contrast image, yielding a map of Hounsfield unit (HU) enhancement. These subtractionmore » image data sets hypothetically represent perfused blood volume, a surrogate for perfusion. In an IACUC-approved clinical trial, we acquired pre- and post-contrast CT scans in the prone posture for six anesthetized, mechanically-ventilated dogs. The elastix algorithm was used for DIR. The registration accuracy was quantified using the target registration errors (TREs) for 50 pulmonary landmarks in each dog. The gradient of HU enhancement between gravity-dependent (ventral) and non-dependent (dorsal) regions was evaluated to quantify the known effect of gravity, i.e., greater perfusion in ventral regions. Results: The lung volume difference between the two scans was 4.3±3.5% on average (range 0.3%–10.1%). DIR demonstrated an average TRE of 0.7±1.0 mm. HU enhancement in lung parenchyma was 34±10 HU on average and varied considerably between individual dogs, indicating the need for improvement of the contrast injection protocol. HU enhancement in ventral (gravity-dependent) regions was found to be greater than in dorsal regions. A population average ventral-to-dorsal gradient of HU enhancement was strong (R{sup 2}=0.94) and statistically significant (p<0.01). Conclusion: This canine study demonstrated relatively accurate DIR and a strong ventral-to-dorsal gradient of HU enhancement, providing proof-of-principle for single-energy CT pulmonary perfusion imaging. This ongoing study will enroll more dogs and investigate the physiological significance. This study was supported by a Philips Healthcare/Radiological Society of North America (RSNA) Research Seed Grant (RSD1458)« less

Noninvasive Imaging of PSMA in prostate tumors with (89)Zr-Labeled huJ591 engineered antibody fragments: the faster alternatives.

PubMed

Viola-Villegas, Nerissa Therese; Sevak, Kuntal K; Carlin, Sean D; Doran, Michael G; Evans, Henry W; Bartlett, Derek W; Wu, Anna M; Lewis, Jason S

2014-11-03

Engineered antibody fragments offer faster delivery with retained tumor specificity and rapid clearance from nontumor tissues. Here, we demonstrate that positron emission tomography (PET) based detection of prostate specific membrane antigen (PSMA) in prostatic tumor models using engineered bivalent antibodies built on single chain fragments (scFv) derived from the intact antibody, huJ591, offers similar tumor delineating properties but with the advantage of rapid targeting and imaging. (89)Zr-radiolabeled huJ591 scFv (dimeric scFv-CH3; (89)Zr-Mb) and cysteine diabodies (dimeric scFv; (89)Zr-Cys-Db) demonstrated internalization and similar Kds (∼2 nM) compared to (89)Zr-huJ591 in PSMA(+) cells. Tissue distribution assays established the specificities of both (89)Zr-Mb and (89)Zr-Cys-Db for PSMA(+) xenografts (6.2 ± 2.5% ID/g and 10.2 ± 3.4% ID/g at 12 h p.i. respectively), while minimal accumulation in PSMA(-) tumors was observed. From the PET images, (89)Zr-Mb and (89)Zr-Cys-Db exhibited faster blood clearance than the parent huJ591 while tumor-to-muscle ratios for all probes show comparable values across all time points. Ex vivo autoradiography and histology assessed the distribution of the probes within the tumor. Imaging PSMA-expressing prostate tumors with smaller antibody fragments offers rapid tumor accumulation and accelerated clearance; hence, shortened wait periods between tracer administration and high-contrast tumor imaging and lower dose-related toxicity are potentially realized.

Prediction of calcium level in melamine-related urinary calculi with helical CT: diagnostic performance evaluation and clinical significance.

PubMed

Yuan, Li; Xiaorui, Ru; Gang, Huang; Xinsheng, Xi; Xiaogang, Huang; Li, Dong; Yirong, Chen

2012-06-01

The aim of the study was to investigate the relationship between CT-attenuation and stone calcium level in melamine-related urinary calculi (MRUC). A total of 25 MRUC with known composition and calcium level were included (11 uric acid stones, 2 calcium oxalate stones and 12 mixture stones of uric acid and calcium oxalate). Of all, 18 renal stones accepted alkalization therapy except for 5 lower urinary tract stones and 2 stones of unknown position. With well-matched composition, 61 adult urinary stones were included as controls. Every stone was scanned by helical CT (80 kV/120 kV, 300 mA, pitch 0.625 mm) and the highest CT-attenuation value measured. CT-attenuation values of MRUC increased gradually from uric acid stones, mixture stones to calcium oxalate stones, but were always lower than the values of controls. Furthermore, a strong positive correlation was found between stone CT-attenuation value and stone calcium level (n = 25, r (80kV) = 0.883, p = 0.000; r (120kV) = 0.855, p = 0.000). Compared with alkalization-therapy-alone group, stone CT-attenuation values and stone calcium level in the comprehensive-therapy group were significantly greater (CT(80kV) 1,057 ± 639 vs. 172 ± 61 HU, p = 0.001; CT(120kV) 783 ± 476 vs. 162 ± 60 HU, p = 0.001; Ca 19.83 ± 7.48% vs. 1.30 ± 1.51%, p = 0.000). Fisher's exact test suggested that the stones with higher CT-attenuation values tended to resist alkalization when 400 HU served as the cutoff value (P (80kV) = 0.002, P (120kV) = 0.000). In conclusion, the study was the first to illustrate that the CT-attenuation value could reflect calcium level in MRUC and found that stones with higher CT-attenuation value were not amenable to alkalization because they probably contained greater calcium. For those patients, we believe that comprehensive therapy will be the best choice.

RNA-binding protein HuR autoregulates its expression by promoting alternative polyadenylation site usage

PubMed Central

Dai, Weijun; Zhang, Gen; Makeyev, Eugene V.

2012-01-01

RNA-binding protein HuR modulates the stability and translational efficiency of messenger RNAs (mRNAs) encoding essential components of the cellular proliferation, growth and survival pathways. Consistent with these functions, HuR levels are often elevated in cancer cells and reduced in senescent and quiescent cells. However, the molecular mechanisms that control HuR expression are poorly understood. Here we show that HuR protein autoregulates its abundance through a negative feedback loop that involves interaction of the nuclear HuR protein with a GU-rich element (GRE) overlapping with the HuR major polyadenylation signal (PAS2). An increase in the cellular HuR protein levels stimulates the expression of long HuR mRNA species containing an AU-rich element (ARE) that destabilizes the mRNAs and thus reduces the protein production output. The PAS2 read-through occurs due to a reduced recruitment of the CstF-64 subunit of the pre-mRNA cleavage stimulation factor in the presence of the GRE-bound HuR. We propose that this mechanism maintains HuR homeostasis in proliferating cells. Since only the nuclear HuR is expected to contribute to the auto-regulation, our model may explain the longstanding observation that the increase in the total HuR expression in cancer cells often correlates with the accumulation of its substantial fraction in the cytoplasm. PMID:21948791

RNA-binding protein HuR autoregulates its expression by promoting alternative polyadenylation site usage.

PubMed

Dai, Weijun; Zhang, Gen; Makeyev, Eugene V

2012-01-01

RNA-binding protein HuR modulates the stability and translational efficiency of messenger RNAs (mRNAs) encoding essential components of the cellular proliferation, growth and survival pathways. Consistent with these functions, HuR levels are often elevated in cancer cells and reduced in senescent and quiescent cells. However, the molecular mechanisms that control HuR expression are poorly understood. Here we show that HuR protein autoregulates its abundance through a negative feedback loop that involves interaction of the nuclear HuR protein with a GU-rich element (GRE) overlapping with the HuR major polyadenylation signal (PAS2). An increase in the cellular HuR protein levels stimulates the expression of long HuR mRNA species containing an AU-rich element (ARE) that destabilizes the mRNAs and thus reduces the protein production output. The PAS2 read-through occurs due to a reduced recruitment of the CstF-64 subunit of the pre-mRNA cleavage stimulation factor in the presence of the GRE-bound HuR. We propose that this mechanism maintains HuR homeostasis in proliferating cells. Since only the nuclear HuR is expected to contribute to the auto-regulation, our model may explain the longstanding observation that the increase in the total HuR expression in cancer cells often correlates with the accumulation of its substantial fraction in the cytoplasm.

Computed tomographic venography for varicose veins of the lower extremities: prospective comparison of 80-kVp and conventional 120-kVp protocols.

PubMed

Cho, Eun-Suk; Kim, Joo Hee; Kim, Sungjun; Yu, Jeong-Sik; Chung, Jae-Joon; Yoon, Choon-Sik; Lee, Hyeon-Kyeong; Lee, Kyung Hee

2012-01-01

To prospectively investigate the feasibility of an 80-kilovolt (peak) (kVp) protocol in computed tomographic venography for varicose veins of the lower extremities by comparison with conventional 120-kVp protocol. Attenuation values and signal-to-noise ratio of iodine contrast medium (CM) were determined in a water phantom for 2 tube voltages (80 kVp and 120 kVp). Among 100 patients, 50 patients were scanned with 120 kVp and 150 effective milliampere second (mAs(eff)), and the other 50 patients were scanned with 80 kVp and 390 mAs(eff) after the administration of 1.7-mL/kg CM (370 mg of iodine per milliliter). The 2 groups were compared for venous attenuation, contrast-to-noise ratio, and subjective degree of venous enhancement, image noise, and overall diagnostic image quality. In the phantom, the attenuation value and signal-to-noise ratio value for iodine CM at 80 kVp were 63.8% and 33.0% higher, respectively, than those obtained at 120 kVp. The mean attenuation of the measured veins of the lower extremities was 148.3 Hounsfield units (HU) for the 80-kVp protocol and 94.8 HU for the 120-kVp protocol. Contrast-to-noise ratio was also significantly higher with the 80-kVp protocol. The overall diagnostic image quality of the 3-dimensional volume-rendered images was good with both protocols. The subjective score for venous enhancement was higher at the 80-kVp protocol. The mean volume computed tomography dose index of the 80-kVp (5.6 mGy) protocol was 23.3% lower than that of the 120-kVp (7.3 mGy) protocol. The use of the 80-kVp protocol improved overall venous attenuation, especially in perforating vein, and provided similarly high diagnostic image quality with a lower radiation dose when compared to the conventional 120-kVp protocol.

Advanced quantitative methods in correlating sarcopenic muscle degeneration with lower extremity function biometrics and comorbidities

PubMed Central

Gíslason, Magnús; Sigurðsson, Sigurður; Guðnason, Vilmundur; Harris, Tamara; Carraro, Ugo; Gargiulo, Paolo

2018-01-01

Sarcopenic muscular degeneration has been consistently identified as an independent risk factor for mortality in aging populations. Recent investigations have realized the quantitative potential of computed tomography (CT) image analysis to describe skeletal muscle volume and composition; however, the optimum approach to assessing these data remains debated. Current literature reports average Hounsfield unit (HU) values and/or segmented soft tissue cross-sectional areas to investigate muscle quality. However, standardized methods for CT analyses and their utility as a comorbidity index remain undefined, and no existing studies compare these methods to the assessment of entire radiodensitometric distributions. The primary aim of this study was to present a comparison of nonlinear trimodal regression analysis (NTRA) parameters of entire radiodensitometric muscle distributions against extant CT metrics and their correlation with lower extremity function (LEF) biometrics (normal/fast gait speed, timed up-and-go, and isometric leg strength) and biochemical and nutritional parameters, such as total solubilized cholesterol (SCHOL) and body mass index (BMI). Data were obtained from 3,162 subjects, aged 66–96 years, from the population-based AGES-Reykjavik Study. 1-D k-means clustering was employed to discretize each biometric and comorbidity dataset into twelve subpopulations, in accordance with Sturges’ Formula for Class Selection. Dataset linear regressions were performed against eleven NTRA distribution parameters and standard CT analyses (fat/muscle cross-sectional area and average HU value). Parameters from NTRA and CT standards were analogously assembled by age and sex. Analysis of specific NTRA parameters with standard CT results showed linear correlation coefficients greater than 0.85, but multiple regression analysis of correlative NTRA parameters yielded a correlation coefficient of 0.99 (P<0.005). These results highlight the specificities of each muscle quality metric to LEF biometrics, SCHOL, and BMI, and particularly highlight the value of the connective tissue regime in this regard. PMID:29513690

Advanced quantitative methods in correlating sarcopenic muscle degeneration with lower extremity function biometrics and comorbidities.

PubMed

Edmunds, Kyle; Gíslason, Magnús; Sigurðsson, Sigurður; Guðnason, Vilmundur; Harris, Tamara; Carraro, Ugo; Gargiulo, Paolo

2018-01-01

Sarcopenic muscular degeneration has been consistently identified as an independent risk factor for mortality in aging populations. Recent investigations have realized the quantitative potential of computed tomography (CT) image analysis to describe skeletal muscle volume and composition; however, the optimum approach to assessing these data remains debated. Current literature reports average Hounsfield unit (HU) values and/or segmented soft tissue cross-sectional areas to investigate muscle quality. However, standardized methods for CT analyses and their utility as a comorbidity index remain undefined, and no existing studies compare these methods to the assessment of entire radiodensitometric distributions. The primary aim of this study was to present a comparison of nonlinear trimodal regression analysis (NTRA) parameters of entire radiodensitometric muscle distributions against extant CT metrics and their correlation with lower extremity function (LEF) biometrics (normal/fast gait speed, timed up-and-go, and isometric leg strength) and biochemical and nutritional parameters, such as total solubilized cholesterol (SCHOL) and body mass index (BMI). Data were obtained from 3,162 subjects, aged 66-96 years, from the population-based AGES-Reykjavik Study. 1-D k-means clustering was employed to discretize each biometric and comorbidity dataset into twelve subpopulations, in accordance with Sturges' Formula for Class Selection. Dataset linear regressions were performed against eleven NTRA distribution parameters and standard CT analyses (fat/muscle cross-sectional area and average HU value). Parameters from NTRA and CT standards were analogously assembled by age and sex. Analysis of specific NTRA parameters with standard CT results showed linear correlation coefficients greater than 0.85, but multiple regression analysis of correlative NTRA parameters yielded a correlation coefficient of 0.99 (P<0.005). These results highlight the specificities of each muscle quality metric to LEF biometrics, SCHOL, and BMI, and particularly highlight the value of the connective tissue regime in this regard.

Noninvasive microwave ablation zone radii estimation using x-ray CT image analysis.

PubMed

Weiss, Noam; Goldberg, S Nahum; Nissenbaum, Yitzhak; Sosna, Jacob; Azhari, Haim

2016-08-01

The aims of this study were to noninvasively and automatically estimate both the radius of the ablated liver tissue and the radius encircling the treated zone, which also defines where the tissue is definitely untreated during a microwave (MW) thermal ablation procedure. Fourteen ex vivo bovine fresh liver specimens were ablated at 40 W using a 14 G microwave antenna, for durations of 3, 6, 8, and 10 min. The tissues were scanned every 5 s during the ablation using an x-ray CT scanner. In order to estimate the radius of the ablation zone, the acquired images were transformed into a polar presentation by displaying the Hounsfield units (HU) as a function of angle and radius. From this polar presentation, the average HU radial profile was analyzed at each time point and the ablation zone radius was estimated. In addition, textural analysis was applied to the original CT images. The proposed algorithm identified high entropy regions and estimated the treated zone radius per time. The estimated ablated zone radii as a function of treatment durations were compared, by means of correlation coefficient and root mean square error (RMSE) to gross pathology measurements taken immediately post-treatment from similarly ablated tissue. Both the estimated ablation radii and the treated zone radii demonstrated strong correlation with the measured gross pathology values (R(2) ≥ 0.89 and R(2) ≥ 0.86, respectively). The automated ablation radii estimation had an average discrepancy of less than 1 mm (RMSE = 0.65 mm) from the gross pathology measured values, while the treated zone radii showed a slight overestimation of approximately 1.5 mm (RMSE = 1.6 mm). Noninvasive monitoring of MW ablation using x-ray CT and image analysis is feasible. Automatic estimations of the ablation zone radius and the radius encompassing the treated zone that highly correlate with actual ablation measured values can be obtained. This technique can therefore potentially be used to obtain real time monitoring and improve the clinical outcome.

SU-G-IeP1-06: Estimating Relative Tissue Density From Quantitative MR Images: A Novel Perspective for MRI-Only Heterogeneity Corrected Dose Calculation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Soliman, A; Hashemi, M; Safigholi, H

Purpose: To explore the feasibility of extracting the relative density from quantitative MRI measurements as well as estimate a correlation between the extracted measures and CT Hounsfield units. Methods: MRI has the ability to separate water and fat signals, producing two separate images for each component. By performing appropriate corrections on the separated images, quantitative measurement of water and fat mass density can be estimated. This work aims to test this hypothesis on 1.5T.Peanut oil was used as fat-representative, while agar as water-representative. Gadolinium Chloride III and Sodium Chloride were added to the agar solution to adjust the relaxation timesmore » and the medium conductivity, respectively. Peanut oil was added to the agar solution with different percentages: 0%, 3%, 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90% and 100%. The phantom was scanned on 1.5T GE Optima 450W with the body coil using a multigradient echo sequences. Water/fat separation were performed while correcting for main field (B0) inhomogeneity and T{sub 2}* relaxation time. B1+ inhomogeneities were ignored. The phantom was subsequently scanned on a Philips Brilliance CT Big Bore. MR-corrected fat signal from all vials were normalized to 100% fat signal. CT Hounsfield values were then compared to those obtained from the normalized MR-corrected fat values as well as to the phantom for validation. Results: Good agreement were found between CT HU and the MR-extracted fat values (R{sup 2} = 0.98). CT HU also showed excellent agreement with the prepared fat fractions (R{sup 2}=0.99). Vials with 70%, 80%, and 90% fat percentages showed inhomogeneous distributions, however their results were included for completion. Conclusion: Quantitative MRI water/fat imaging can be potentially used to extract the relative tissue density. Further in-vivo validation are required.« less

SU-E-J-272: Auto-Segmentation of Regions with Differentiating CT Numbers for Treatment Response Assessment

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yang, C; Noid, G; Dalah, E

2015-06-15

Purpose: It has been reported recently that the change of CT number (CTN) during and after radiation therapy (RT) may be used to assess RT response. The purpose of this work is to develop a tool to automatically segment the regions with differentiating CTN and/or with change of CTN in a series of CTs. Methods: A software tool was developed to identify regions with differentiating CTN using K-mean Cluster of CT numbers and to automatically delineate these regions using convex hull enclosing method. Pre- and Post-RT CT, PET, or MRI images acquired for sample lung and pancreatic cancer cases weremore » used to test the software tool. K-mean cluster of CT numbers within the gross tumor volumes (GTVs) delineated based on PET SUV (standard uptake value of fludeoxyglucose) and/or MRI ADC (apparent diffusion coefficient) map was analyzed. The cluster centers with higher value were considered as active tumor volumes (ATV). The convex hull contours enclosing preset clusters were used to delineate these ATVs with color washed displays. The CTN defined ATVs were compared with the SUV- or ADC-defined ATVs. Results: CTN stability of the CT scanner used to acquire the CTs in this work is less than 1.5 Hounsfield Unit (HU) variation annually. K-mean cluster centers in the GTV have difference of ∼20 HU, much larger than variation due to CTN stability, for the lung cancer cases studied. The dice coefficient between the ATVs delineated based on convex hull enclosure of high CTN centers and the PET defined GTVs based on SUV cutoff value of 2.5 was 90(±5)%. Conclusion: A software tool was developed using K-mean cluster and convex hull contour to automatically segment high CTN regions which may not be identifiable using a simple threshold method. These CTN regions were reasonably overlapped with the PET or MRI defined GTVs.« less

Accuracy of Dual-Energy Virtual Monochromatic CT Numbers: Comparison between the Single-Source Projection-Based and Dual-Source Image-Based Methods.

PubMed

Ueguchi, Takashi; Ogihara, Ryota; Yamada, Sachiko

2018-03-21

To investigate the accuracy of dual-energy virtual monochromatic computed tomography (CT) numbers obtained by two typical hardware and software implementations: the single-source projection-based method and the dual-source image-based method. A phantom with different tissue equivalent inserts was scanned with both single-source and dual-source scanners. A fast kVp-switching feature was used on the single-source scanner, whereas a tin filter was used on the dual-source scanner. Virtual monochromatic CT images of the phantom at energy levels of 60, 100, and 140 keV were obtained by both projection-based (on the single-source scanner) and image-based (on the dual-source scanner) methods. The accuracy of virtual monochromatic CT numbers for all inserts was assessed by comparing measured values to their corresponding true values. Linear regression analysis was performed to evaluate the dependency of measured CT numbers on tissue attenuation, method, and their interaction. Root mean square values of systematic error over all inserts at 60, 100, and 140 keV were approximately 53, 21, and 29 Hounsfield unit (HU) with the single-source projection-based method, and 46, 7, and 6 HU with the dual-source image-based method, respectively. Linear regression analysis revealed that the interaction between the attenuation and the method had a statistically significant effect on the measured CT numbers at 100 and 140 keV. There were attenuation-, method-, and energy level-dependent systematic errors in the measured virtual monochromatic CT numbers. CT number reproducibility was comparable between the two scanners, and CT numbers had better accuracy with the dual-source image-based method at 100 and 140 keV. Copyright © 2018 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.

SU-E-J-152: Evaluation of TrueBeam OBI V. 1.5 CBCT Performance in An Adaptive RT Environment

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gardner, S; Studenski, M; Giaddui, T

2014-06-01

Purpose: To evaluate the image quality and imaging dose of the Varian TrueBeam OBIv.1.5 CBCT system in a clinical adaptive radiation therapy environment, simulated by changing phantom thickness. Methods: Various OBI CBCT protocols(Head, Pelvis, Thorax, Spotlight) were used to acquire images of Catphan504 phantom(nominal phantom thickness and 10 cm additional phantom thickness). The images were analyzed for low contrast detectability(CNR), uniformity(UI), and HU sensitivity. These results were compared to the same image sets for planning CT(pCT)(GE LightSpeed 16- slice). Imaging dose measurements were performed with Gafchromic XRQA2 film for various OBI protocols (Pelvis, Thorax, Spotlight) in a pelvic-sized phantom(nominal thicknessmore » and 4cm additional thickness). Dose measurements were acquired in the interior and at the surface of the phantom. Results: The nominal CNR[additional thickness CNR] for OBI was—Pelvis:1.45[0.81],Thorax:0.86[0.48], Spotlight:0.67[0.39],Head:0.28 [0.10]. The nominal CNR[additional thickness CNR] for pCT was— Pelvis:0.87[0.41],Head:0.60[0.22]. The nominal UI[additional thickness UI] for OBI was—Pelvis:11.5[24.1],Thorax:17.0[20.6], Spotlight:23.2[23.2], Head:15.6[59.9]. The nominal UI[additional thickness UI] for pCT was— Pelvis:9.2[8.6],Head:2.1[2.9]. The HU difference(averaged over all material inserts) between nominal and additional thickness scans for OBI: 8.26HU(Pelvis), 33.39HU(Thorax), 178.98HU(Head), 108.20HU (Spotlight); for pCT: 16.00HU(Pelvis), 19.85HU(Head). Uncertainties in electron density were calculated based on HU values with varying phantom thickness. Average electron-density deviations (ρ(water)=1)for GE-Pelvis, GE-Head, OBI-Pelvis, OBI-Thorax, OBI-Spotlight, and OBI-Head were: 0.0182, 0.0180, 0.0058, 0.0478, 0.2750, and 0.3115, respectively.The average phantom interior dose was(OBI-nominal):2.35cGy(Pelvis), 0.60cGy(Thorax), 1.87cGy(Spotlight); OBI-increased thickness: 1.77cGy(Pelvis), 0.43cGy(Thorax), 1.53cGy (Spotlight). Average surface dose(OBI-nominal): 2.29cGy(Pelvis), 0.56cGy(Thorax), 1.79cGy (Spotlight); OBI-increased thickness: 1.94cGy(Pelvis), 0.48cGy(Thorax), 1.47cGy (Spotlight). Conclusion: The OBI-Pelvis protocol offered comparable CNR and HU constancy to pCT for each geometry; other protocols, particularly Spotlight and Head, exhibited lower HU constancy and CNR. The uniformity of pCT was superior to OBI for all protocols. CNR and UI were degraded for both systems/scan types with increased thickness. The OBI interior dose decreased by approximately 30% with additional thickness. This work was funded, in part, under a grant with the Pennsylvania Department of Health. The Department of Health specifically declaims responsibility for any analyses, interpretations, or conclusions.« less

Dual-Energy Computed Tomography for the Characterization of Intracranial Hemorrhage and Calcification: A Systematic Approach in a Phantom System.

PubMed

Nute, Jessica L; Jacobsen, Megan C; Chandler, Adam; Cody, Dianna D; Schellingerhout, Dawid

2017-01-01

The aim of this study was to develop a diagnostic framework for distinguishing calcific from hemorrhagic cerebral lesions using dual-energy computed tomography (DECT) in an anthropomorphic phantom system. An anthropomorphic phantom was designed to mimic the CT imaging characteristics of the human head. Cylindrical lesion models containing either calcium or iron, mimicking calcification or hemorrhage, respectively, were developed to exhibit matching, and therefore indistinguishable, single-energy CT (SECT) attenuation values from 40 to 100 HU. These lesion models were fabricated at 0.5, 1, and 1.5 cm in diameter and positioned in simulated cerebrum and skull base locations within the anthropomorphic phantom. All lesion sizes were modeled in the cerebrum, while only 1.5-cm lesions were modeled in the skull base. Images were acquired using a GE 750HD CT scanner and an expansive dual-energy protocol that covered variations in dose (36.7-132.6 mGy CTDIvol, n = 12), image thickness (0.625-5 mm, n = 4), and reconstruction filter (soft, standard, detail, n = 3) for a total of 144 unique technique combinations. Images representing each technique combination were reconstructed into water and calcium material density images, as well as a monoenergetic image chosen to mimic the attenuation of a 120-kVp SECT scan. A true single-energy routine brain protocol was also included for verification of lesion SECT attenuation. Points representing the 3 dual-energy reconstructions were plotted into a 3-dimensional space (water [milligram/milliliter], calcium [milligram/milliliter], monoenergetic Hounsfield unit as x, y, and z axes, respectively), and the distribution of points analyzed using 2 approaches: support vector machines and a simple geometric bisector (GB). Each analysis yielded a plane of optimal differentiation between the calcification and hemorrhage lesion model distributions. By comparing the predicted lesion composition to the known lesion composition, we identified the optimal combination of CTDIvol, image thickness, and reconstruction filter to maximize differentiation between the lesion model types. To validate these results, a new set of hemorrhage and calcification lesion models were created, scanned in a blinded fashion, and prospectively classified using the planes of differentiation derived from support vector machine and GB methods. Accuracy of differentiation improved with increasing dose (CTDIvol) and image thickness. Reconstruction filter had no effect on the accuracy of differentiation. Using an optimized protocol consisting of the maximum CTDIvol of 132.6 mGy, 5-mm-thick images, and a standard filter, hemorrhagic and calcific lesion models with equal SECT attenuation (Hounsfield unit) were differentiated with over 90% accuracy down to 70 HU for skull base lesions of 1.5 cm, and down to 100 HU, 60 HU, and 60 HU for cerebrum lesions of 0.5, 1.0, and 1.5 cm, respectively. The analytic method that yielded the best results was a simple GB plane through the 3-dimensional DECT space. In the validation study, 96% of unknown lesions were correctly classified across all lesion sizes and locations investigated. We define the optimal scan parameters and expected limitations for the accurate classification of hemorrhagic versus calcific cerebral lesions in an anthropomorphic phantom with DECT. Although our proposed DECT protocol represents an increase in dose compared with routine brain CT, this method is intended as a specialized evaluation of potential brain hemorrhage and is thus counterbalanced by increased diagnostic benefit. This work provides justification for the application of this technique in human clinical trials.

Development of a Test Method for the Evaluation of DNA Damage in Mouse Spermatogonial Stem Cells

PubMed Central

Jeon, Hye Lyun; Yi, Jung-Sun; Kim, Tae Sung; Oh, Youkyung; Lee, Hye Jeong; Lee, Minseong; Bang, Jin Seok; Ko, Kinarm; Ahn, Il Young; Ko, Kyungyuk; Kim, Joohwan; Park, Hye-Kyung; Lee, Jong Kwon; Sohn, Soo Jung

2017-01-01

Although alternative test methods based on the 3Rs (Replacement, Reduction, Refinement) are being developed to replace animal testing in reproductive and developmental toxicology, they are still in an early stage. Consequently, we aimed to develop alternative test methods in male animals using mouse spermatogonial stem cells (mSSCs). Here, we modified the OECD TG 489 and optimized the in vitro comet assay in our previous study. This study aimed to verify the validity of in vitro tests involving mSSCs by comparing their results with those of in vivo tests using C57BL/6 mice by gavage. We selected hydroxyurea (HU), which is known to chemically induce male reproductive toxicity. The 50% inhibitory concentration (IC50) value of HU was 0.9 mM, as determined by the MTT assay. In the in vitro comet assay, % tail DNA and Olive tail moment (OTM) after HU administration increased significantly, compared to the control. Annexin V, PI staining and TUNEL assays showed that HU caused apoptosis in mSSCs. In order to compare in vitro tests with in vivo tests, the same substances were administered to male C57BL/6 mice. Reproductive toxicity was observed at 25, 50, 100, and 200 mg/kg/day as measured by clinical measures of reduction in sperm motility and testicular weight. The comet assay, DCFH-DA assay, H&E staining, and TUNEL assay were also performed. The results of the test with C57BL/6 mice were similar to those with mSSCs for HU treatment. Finally, linear regression analysis showed a strong positive correlation between results of in vitro tests and those of in vivo. In conclusion, the present study is the first to demonstrate the effect of HU-induced DNA damage, ROS formation, and apoptosis in mSSCs. Further, the results of the current study suggest that mSSCs could be a useful model to predict male reproductive toxicity. PMID:28443181

[Anemia management in haemodialysis. EuCliD database in Spain].

PubMed

Avilés, B; Coronel, F; Pérez-García, R; Marcelli, D; Orlandini, G; Ayala, J A; Rentero, R

2002-01-01

We present the results on Anaemia Management in Fresenius Medical Care Spain dialysis centres as reported by EuCliD (European Clinical Database), evaluating a population of 4,426 patients treated in Spain during the year 2001. To analyse the erythropoietin dose and the haemoglobin levels we divided the population in two groups according to the time with dialysis treatment: patients treated less than six months and patients between six months, and four years on therapy. We compared our results with the evidence based recommendations Guidelines: the European Best Practice Guidelines (EBPG) and the US National Kidney Foundation (NKF-K/DOQI). We also compared our results with those presented by the ESAM2 on 2,618 patients on dialysis in Spain carried out in the second half of the year 2000. We observed that 70% of the population reaches an haemoglobin value higher that 11 g/dl, with a mean erythropoietin (rHu-EPO) dose of 111.9 Ul/kg weight/week (n = 3,700; SD 74.9). However, for those patients on treatment for less than six months, the mean Haemoglobin only reaches 10.65 g/dl (n = 222; SD 1.4). The rHu-EPO was administrated subcutaneously in 70.2% of the patients. About the iron therapy, 86% of the patients received iron treatment and the administration route was intravenous in 93% of the population. The ferritin levels were below 100 micrograms/dl in 10% of the patients and 26.4% showed a transferrin saturation index (TSAT) below 20%. The erythropoieting resistance index (ERI), as rHu-EPO/haemoglobin, has been used to evaluate the response to rHu-Epo, according to different variables. It was observed that the following factors lead to a higher rHu-EPO resistance: intravenous rHu-EPO as administration route, the presence of hypoalbuminemia, increase of protein C reactive, Transferrin saturation below 20% and starting dialysis during the last six months.

Single-Dose Primaquine in a Preclinical Model of Glucose-6-Phosphate Dehydrogenase Deficiency: Implications for Use in Malaria Transmission-Blocking Programs

PubMed Central

Wickham, Kristina S.; Baresel, Paul C.; Sousa, Jason; Vuong, Chau T.; Reichard, Gregory A.; Campo, Brice; Tekwani, Babu L.; Walker, Larry A.

2016-01-01

Individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency (G6PDd) are at risk for developing hemolytic anemia when given the antimalarial drug primaquine (PQ). The WHO Evidence Review Group released a report suggesting that mass administration of a single dose of PQ at 0.25 mg of base/kg of body weight (mpk) (mouse equivalent of 3.125 mpk) could potentially reduce malaria transmission based on its gametocytocidal activity and could be safely administered to G6PD-deficient individuals, but there are limited safety data available confirming the optimum single dose of PQ. A single-dose administration of PQ was therefore assessed in our huRBC-SCID mouse model used to predict hemolytic toxicity with respect to G6PD deficiency. In this model, nonobese diabetic (NOD)/SCID mice are engrafted with human red blood cells (huRBC) from donors with the African or Mediterranean variant of G6PDd (A-G6PDd or Med-G6PDd, respectively) and demonstrate dose-dependent sensitivity to PQ. In mice engrafted with A-G6PD-deficient huRBC, single-dose PQ at 3.125, 6.25, or 12.5 mpk had no significant loss of huRBC compared to the vehicle control group. In contrast, in mice engrafted with Med-G6PDd huRBC, a single dose of PQ at 3.125, 6.25, or 12.5 mpk resulted in a significant, dose-dependent loss of huRBC compared to the value for the vehicle control group. Our data suggest that administration of a single low dose of 0.25 mpk of PQ could induce hemolytic anemia in Med-G6PDd individuals but that use of single-dose PQ at 0.25 mpk as a gametocytocidal drug to block transmission would be safe in areas where A-G6PDd predominates. PMID:27458212

Single-Dose Primaquine in a Preclinical Model of Glucose-6-Phosphate Dehydrogenase Deficiency: Implications for Use in Malaria Transmission-Blocking Programs.

PubMed

Wickham, Kristina S; Baresel, Paul C; Marcsisin, Sean R; Sousa, Jason; Vuong, Chau T; Reichard, Gregory A; Campo, Brice; Tekwani, Babu L; Walker, Larry A; Rochford, Rosemary

2016-10-01

Individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency (G6PDd) are at risk for developing hemolytic anemia when given the antimalarial drug primaquine (PQ). The WHO Evidence Review Group released a report suggesting that mass administration of a single dose of PQ at 0.25 mg of base/kg of body weight (mpk) (mouse equivalent of 3.125 mpk) could potentially reduce malaria transmission based on its gametocytocidal activity and could be safely administered to G6PD-deficient individuals, but there are limited safety data available confirming the optimum single dose of PQ. A single-dose administration of PQ was therefore assessed in our huRBC-SCID mouse model used to predict hemolytic toxicity with respect to G6PD deficiency. In this model, nonobese diabetic (NOD)/SCID mice are engrafted with human red blood cells (huRBC) from donors with the African or Mediterranean variant of G6PDd (A-G6PDd or Med-G6PDd, respectively) and demonstrate dose-dependent sensitivity to PQ. In mice engrafted with A-G6PD-deficient huRBC, single-dose PQ at 3.125, 6.25, or 12.5 mpk had no significant loss of huRBC compared to the vehicle control group. In contrast, in mice engrafted with Med-G6PDd huRBC, a single dose of PQ at 3.125, 6.25, or 12.5 mpk resulted in a significant, dose-dependent loss of huRBC compared to the value for the vehicle control group. Our data suggest that administration of a single low dose of 0.25 mpk of PQ could induce hemolytic anemia in Med-G6PDd individuals but that use of single-dose PQ at 0.25 mpk as a gametocytocidal drug to block transmission would be safe in areas where A-G6PDd predominates. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Hydroxyurea prescription, availability and use for children with sickle cell disease in Italy: Results of a National Multicenter survey.

PubMed

Colombatti, Raffaella; Palazzi, Giovanni; Masera, Nicoletta; Notarangelo, Lucia Dora; Bonetti, Elisa; Samperi, Piera; Barone, Angelica; Perrotta, Silverio; Facchini, Elena; Miano, Maurizio; Del Vecchio, Giovanni Carlo; Guerzoni, Maria Elena; Corti, Paola; Menzato, Federica; Cesaro, Simone; Casale, Maddalena; Rigano, Paolo; Forni, Gian Luca; Russo, Giovanna; Sainati, Laura

2018-02-01

The number of patients with sickle cell disease (SCD) has increased in Italy in the past decade due to immigration. In spite of the established efficacy of hydroxyurea (HU) in childhood, population-based data regarding its prescription and effectiveness come mainly from studies performed in adults or outside Europe. The Hydroxyurea in SCD: A Large Nation-wide Cohort Study from Italy was a retrospective cohort study of adult and pediatric patients with SCD attending 32 centers. Pediatric data are analyzed separately. Out of 504 children followed in 11 centers, 206 (40%) were on HU (194 SS/Sβ°, 12 SC/Sß+); 74% came from Sub-Saharian Africa and 18% from Europe. HU therapy indications for SS/Sβ° patients were as follows: 57% painful vaso-occlusive crisis, acute chest syndrome or both, 24% anemia, 8% anemia, and other reasons (the majority had Hb ≤ 8-8.5 g/dl, revealing scarce acceptance of low Hb values by pediatric hematologist). Mean starting dose was 15.5 mg/kg, and dose at full regimen was 17.1 mg/kg. Mean age at HU therapy was 7.68 years, although it was lower for SS/Sβ° patients. Only 10% started HU before 3 years. In 92%, 500 mg capsule was used; in 6%, the galenic was used; and in 2%, 100 mg tablet was used. Significant reduction of clinical events and inpatients admissions, with improvement in hematological parameters, was observed for SS/Sβ° patients and a trend toward improvement for SC/Sß+ patients was also observed. HU effectiveness is demonstrated in a national cohort of children with SCD living in Italy, even at a lower dose than recommended, revealing good adherence to a treatment program by a socially vulnerable group of patients such as immigrants. © 2017 Wiley Periodicals, Inc.

Watersheds, ecoregions and hydrologic units: the appropriate use of each for research and environmental management decisions

Treesearch

James Glover; James Omernik; Robert Hughes; Glenn Griffith; Marc Weber

2016-01-01

It has long been recognized that conditions at a point on a stream are highly dependent on conditions upgradient within the topographic watershed. The hydrologic unit (HU) system has provided a useful set of nationally consistent, hydrologically based polygons that has allowed for the generalization and tabulation of various conditions within the stream and its valley...

Genetic evolution of recently emerged novel human-like swine H3 influenza A viruses (IAV) in United States swine

USDA-ARS?s Scientific Manuscript database

Introduction Influenza A virus (IAV) is a major cause of respiratory disease in swine. IAV transmission from humans to swine is a major contributor to swine IAV diversity. In 2012, a novel H3N2 with an HA (hu-H3) and NA derived from human seasonal H3N2 was detected in United States (US) swine. The h...

Expression of heat shock protein 72 in atrophied rat skeletal muscles

NASA Technical Reports Server (NTRS)

Oishi, Y.; Ishihara, A.; Talmadge, R. J.; Ohira, Y.; Taniguchi, K.; Matsumoto, H.; Roy, R. R.; Edgerton, V. R.

2001-01-01

Changes in the expression of heat shock protein 72 (HSP72) in response to atrophic-inducing perturbations of muscle involving chronic mechanical unloading and denervation were determined. Adult male Wistar rats were assigned randomly to a sedentary cage control (CON), hind limb unloading (HU, via tail suspension), HU plus tenotomy (HU + TEN), HU plus denervation (HU + DEN), or HU + TEN + DEN group. Tenotomy and DEN involved cutting the Achilles tendon and removing a segment of the sciatic nerve, respectively. After 5 days, HSP72 levels in the soleus of the HU + DEN and HU + TEN + DEN groups were 42 (P < 0.05) and 53% (P < 0.01) less than CON, respectively. Soleus weight decreased in both groups. Heat shock protein 72 levels in the plantaris of the HU + TEN, HU + DEN, and HU + TEN + DEN groups were 31, 25, and 30% lower than CON, respectively (P < 0.05). Plantaris weight decreased in the HU + DEN and HU + TEN + DEN, but not in the HU + TEN group. Hind limb unloading alone had little effect on the HSP72 level in either muscle. Reduced levels of HSP72 were associated with a decreased soleus (r=0.62, P < 0.01) and plantaris (r=0.78, P < 0.001) weight. These results indicate that the levels of HSP72 in both a slow and a fast rat plantarflexor are responsive to a chronic decrease in the levels of loading and/or activation and suggest that the neuromuscular activity level and the presence of innervation of a muscle are important factors that induce HSP72 expression.

ASSESSING RELATIVE BED STABILITY AND EXCESS FINE SEDIMENTS IN STREAMS

EPA Science Inventory

Excess fine sedimentation is recognized as a leading cause of water quality impairment in surface waters in the United States. We developed an index of Relative Bed Stability (RBS) that factors out natural controls on streambed particle size to allow evaluation of the role of hu...

Bringing Space Crisis Stability Down to Earth

DTIC Science & Technology

2015-01-01

President Hu Jintao agreed during one of their first meetings that “the two countries have common interests in promoting the peaceful use of outer...linked, and they are linked not only for the United States, but also in- creasingly for China and other countries that rely on space systems to

Validating and improving CT ventilation imaging by correlating with ventilation 4D-PET/CT using {sup 68}Ga-labeled nanoparticles

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kipritidis, John, E-mail: john.kipritidis@sydney.edu.au; Keall, Paul J.; Siva, Shankar

Purpose: CT ventilation imaging is a novel functional lung imaging modality based on deformable image registration. The authors present the first validation study of CT ventilation using positron emission tomography with{sup 68}Ga-labeled nanoparticles (PET-Galligas). The authors quantify this agreement for different CT ventilation metrics and PET reconstruction parameters. Methods: PET-Galligas ventilation scans were acquired for 12 lung cancer patients using a four-dimensional (4D) PET/CT scanner. CT ventilation images were then produced by applying B-spline deformable image registration between the respiratory correlated phases of the 4D-CT. The authors test four ventilation metrics, two existing and two modified. The two existing metricsmore » model mechanical ventilation (alveolar air-flow) based on Hounsfield unit (HU) change (V{sub HU}) or Jacobian determinant of deformation (V{sub Jac}). The two modified metrics incorporate a voxel-wise tissue-density scaling (ρV{sub HU} and ρV{sub Jac}) and were hypothesized to better model the physiological ventilation. In order to assess the impact of PET image quality, comparisons were performed using both standard and respiratory-gated PET images with the former exhibiting better signal. Different median filtering kernels (σ{sub m} = 0 or 3 mm) were also applied to all images. As in previous studies, similarity metrics included the Spearman correlation coefficient r within the segmented lung volumes, and Dice coefficient d{sub 20} for the (0 − 20)th functional percentile volumes. Results: The best agreement between CT and PET ventilation was obtained comparing standard PET images to the density-scaled HU metric (ρV{sub HU}) with σ{sub m} = 3 mm. This leads to correlation values in the ranges 0.22 ⩽ r ⩽ 0.76 and 0.38 ⩽ d{sub 20} ⩽ 0.68, with r{sup ¯}=0.42±0.16 and d{sup ¯}{sub 20}=0.52±0.09 averaged over the 12 patients. Compared to Jacobian-based metrics, HU-based metrics lead to statistically significant improvements in r{sup ¯} and d{sup ¯}{sub 20} (p < 0.05), with density scaled metrics also showing higher r{sup ¯} than for unscaled versions (p < 0.02). r{sup ¯} and d{sup ¯}{sub 20} were also sensitive to image quality, with statistically significant improvements using standard (as opposed to gated) PET images and with application of median filtering. Conclusions: The use of modified CT ventilation metrics, in conjunction with PET-Galligas and careful application of image filtering has resulted in improved correlation compared to earlier studies using nuclear medicine ventilation. However, CT ventilation and PET-Galligas do not always provide the same functional information. The authors have demonstrated that the agreement can improve for CT ventilation metrics incorporating a tissue density scaling, and also with increasing PET image quality. CT ventilation imaging has clear potential for imaging regional air volume change in the lung, and further development is warranted.« less

TU-A-12A-12: Improved Airway Measurement Accuracy for Low Dose Quantitative CT (qCT) Using Statistical (ASIR), at Reduced DFOV, and High Resolution Kernels in a Phantom and Swine Model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yadava, G; Imai, Y; Hsieh, J

2014-06-15

Purpose: Quantitative accuracy of Iodine Hounsfield Unit (HU) in conventional single-kVp scanning is susceptible to beam-hardening effect. Dual-energy CT has unique capabilities of quantification using monochromatic CT images, but this scanning mode requires the availability of the state-of-the-art CT scanner and, therefore, is limited in routine clinical practice. Purpose of this work was to develop a beam-hardening-correction (BHC) for single-kVp CT that can linearize Iodine projections at any nominal energy, apply this approach to study Iodine response with respect to keV, and compare with dual-energy based monochromatic images obtained from material-decomposition using 80kVp and 140kVp. Methods: Tissue characterization phantoms (Gammexmore » Inc.), containing solid-Iodine inserts of different concentrations, were scanned using GE multi-slice CT scanner at 80, 100, 120, and 140 kVp. A model-based BHC algorithm was developed where Iodine was estimated using re-projection of image volume and corrected through an iterative process. In the correction, the re-projected Iodine was linearized using a polynomial mapping between monochromatic path-lengths at various nominal energies (40 to 140 keV) and physically modeled polychromatic path-lengths. The beam-hardening-corrected 80kVp and 140kVp images (linearized approximately at effective energy of the beam) were used for dual-energy material-decomposition in Water-Iodine basis-pair followed by generation of monochromatic images. Characterization of Iodine HU and noise in the images obtained from singlekVp with BHC at various nominal keV, and corresponding dual-energy monochromatic images, was carried out. Results: Iodine HU vs. keV response from single-kVp with BHC and dual-energy monochromatic images were found to be very similar, indicating that single-kVp data may be used to create material specific monochromatic equivalent using modelbased projection linearization. Conclusion: This approach may enable quantification of Iodine contrast enhancement and potential reduction in injected contrast without using dual-energy scanning. However, in general, dual-energy scanning has unique value in material characterization and quantification, and its value cannot be discounted. GE Healthcare Employee.« less

Activity-dependent expression of ELAV/Hu RBPs and neuronal mRNAs in seizure and cocaine brain.

PubMed

Tiruchinapalli, Dhanrajan M; Caron, Marc G; Keene, Jack D

2008-12-01

Growing evidence indicates that both seizure (glutamate) and cocaine (dopamine) treatment modulate synaptic plasticity within the mesolimbic region of the CNS. Activation of glutamatergic neurons depends on the localized translation of neuronal mRNA products involved in modulating synaptic plasticity. In this study, we demonstrate the dendritic localization of HuR and HuD RNA-binding proteins (RBPs) and their association with neuronal mRNAs following these two paradigms of seizure and cocaine treatment. Both the ubiquitously expressed HuR and neuronal HuD RBPs were detected in different regions as well as within dendrites of the brain and in dissociated neurons. Quantitative analysis revealed an increase in HuR, HuD and p-glycogen synthase kinase 3beta (GSK3beta) protein levels as well as neuronal mRNAs encoding Homer, CaMKIIalpha, vascular early response gene, GAP-43, neuritin, and neuroligin protein products following either seizure or cocaine treatment. Inhibition of the Akt/GSK3beta signaling pathway by acute or chronic LiCl treatment revealed changes in HuR, HuD, pGSK3beta, p-Akt, and beta-catenin protein levels. In addition, a genetically engineered hyperdopaminergic mouse model (dopamine transporter knockout) revealed decreased expression of HuR protein levels, but no significant change was observed in HuD or fragile-X mental retardation protein RBPs. Finally, our data suggest that HuR and HuD RBPs potentially interact directly with neuronal mRNAs important for differentiation and synaptic plasticity.

Early Assessment of Treatment Responses During Radiation Therapy for Lung Cancer Using Quantitative Analysis of Daily Computed Tomography

DOE Office of Scientific and Technical Information (OSTI.GOV)

Paul, Jijo; Yang, Cungeng; Wu, Hui

Purpose: To investigate early tumor and normal tissue responses during the course of radiation therapy (RT) for lung cancer using quantitative analysis of daily computed tomography (CT) scans. Methods and Materials: Daily diagnostic-quality CT scans acquired using CT-on-rails during CT-guided RT for 20 lung cancer patients were quantitatively analyzed. On each daily CT set, the contours of the gross tumor volume (GTV) and lungs were generated and the radiation dose delivered was reconstructed. The changes in CT image intensity (Hounsfield unit [HU]) features in the GTV and the multiple normal lung tissue shells around the GTV were extracted from themore » daily CT scans. The associations between the changes in the mean HUs, GTV, accumulated dose during RT delivery, and patient survival rate were analyzed. Results: During the RT course, radiation can induce substantial changes in the HU histogram features on the daily CT scans, with reductions in the GTV mean HUs (dH) observed in the range of 11 to 48 HU (median 30). The dH is statistically related to the accumulated GTV dose (R{sup 2} > 0.99) and correlates weakly with the change in GTV (R{sup 2} = 0.3481). Statistically significant increases in patient survival rates (P=.038) were observed for patients with a higher dH in the GTV. In the normal lung, the 4 regions proximal to the GTV showed statistically significant (P<.001) HU reductions from the first to last fraction. Conclusion: Quantitative analysis of the daily CT scans indicated that the mean HUs in lung tumor and surrounding normal tissue were reduced during RT delivery. This reduction was observed in the early phase of the treatment, is patient specific, and correlated with the delivered dose. A larger HU reduction in the GTV correlated significantly with greater patient survival. The changes in daily CT features, such as the mean HU, can be used for early assessment of the radiation response during RT delivery for lung cancer.« less

Early Assessment of Treatment Responses During Radiation Therapy for Lung Cancer Using Quantitative Analysis of Daily Computed Tomography.

PubMed

Paul, Jijo; Yang, Cungeng; Wu, Hui; Tai, An; Dalah, Entesar; Zheng, Cheng; Johnstone, Candice; Kong, Feng-Ming; Gore, Elizabeth; Li, X Allen

2017-06-01

To investigate early tumor and normal tissue responses during the course of radiation therapy (RT) for lung cancer using quantitative analysis of daily computed tomography (CT) scans. Daily diagnostic-quality CT scans acquired using CT-on-rails during CT-guided RT for 20 lung cancer patients were quantitatively analyzed. On each daily CT set, the contours of the gross tumor volume (GTV) and lungs were generated and the radiation dose delivered was reconstructed. The changes in CT image intensity (Hounsfield unit [HU]) features in the GTV and the multiple normal lung tissue shells around the GTV were extracted from the daily CT scans. The associations between the changes in the mean HUs, GTV, accumulated dose during RT delivery, and patient survival rate were analyzed. During the RT course, radiation can induce substantial changes in the HU histogram features on the daily CT scans, with reductions in the GTV mean HUs (dH) observed in the range of 11 to 48 HU (median 30). The dH is statistically related to the accumulated GTV dose (R 2  > 0.99) and correlates weakly with the change in GTV (R 2  = 0.3481). Statistically significant increases in patient survival rates (P=.038) were observed for patients with a higher dH in the GTV. In the normal lung, the 4 regions proximal to the GTV showed statistically significant (P<.001) HU reductions from the first to last fraction. Quantitative analysis of the daily CT scans indicated that the mean HUs in lung tumor and surrounding normal tissue were reduced during RT delivery. This reduction was observed in the early phase of the treatment, is patient specific, and correlated with the delivered dose. A larger HU reduction in the GTV correlated significantly with greater patient survival. The changes in daily CT features, such as the mean HU, can be used for early assessment of the radiation response during RT delivery for lung cancer. Copyright © 2017 Elsevier Inc. All rights reserved.

Four-Dimensional CT of the Diaphragm in Children: Initial Experience

PubMed Central

2018-01-01

Objective To evaluate the technical feasibility of four-dimensional (4D) CT for the functional evaluation of the pediatric diaphragm. Materials and Methods In 22 consecutive children (median age 3.5 months, age range 3 days–3 years), 4D CT was performed to assess diaphragm motion. Diaphragm abnormalities were qualitatively evaluated and diaphragm motion was quantitatively measured on 4D CT. Lung density changes between peak inspiration and expiration were measured in the basal lung parenchyma. The diaphragm motions and lung density changes measured on 4D CT were compared between various diaphragm conditions. In 11 of the 22 children, chest sonography was available for comparison. Results Four-dimensional CT demonstrated normal diaphragm (n = 8), paralysis (n = 10), eventration (n = 3), and diffusely decreased motion (n = 1). Chest sonography demonstrated normal diaphragm (n = 2), paralysis (n = 6), eventration (n = 2), and right pleural effusion (n = 1). The sonographic findings were concordant with the 4D CT findings in 90.9% (10/11) of the patients. In diaphragm paralysis, the affected diaphragm motion was significantly decreased compared with the contralateral normal diaphragm motion (−1.1 ± 2.2 mm vs. 7.6 ± 3.8 mm, p = 0.005). The normal diaphragms showed significantly greater motion than the paralyzed diaphragms (4.5 ± 2.1 mm vs. −1.1 ± 2.2 mm, p < 0.0001), while the normal diaphragm motion was significantly smaller than the motion of the contralateral normal diaphragm in paralysis (4.5 ± 2.1 mm vs. 7.6 ± 3.8 mm, p = 0.01). Basal lung density change of the affected side was significantly smaller than that of the contralateral side in diaphragm paralysis (89 ± 73 Hounsfield units [HU] vs. 180 ± 71 HU, p = 0.03), while no significant differences were found between the normal diaphragms and the paralyzed diaphragms (136 ± 66 HU vs. 89 ± 73 HU, p = 0.1) or between the normal diaphragms and the contralateral normal diaphragms in paralysis (136 ± 66 HU vs. 180 ± 71 HU, p = 0.1). Conclusion The functional evaluation of the pediatric diaphragm is feasible with 4D CT in select children. PMID:29354007

Bone density loss on computed tomography at 3-year follow-up in current compared to former male smokers.

PubMed

Pompe, E; Bartstra, J; Verhaar, H J; de Koning, H J; van der Aalst, C M; Oudkerk, M; Vliegenthart, R; Lammers, J-W J; de Jong, P A; Mohamed Hoesein, F A A

2017-04-01

Cigarette smoking negatively affects bone quality and increases fracture risk. Little is known on the effect of smoking cessation and computed tomography (CT)-derived bone mineral density (BMD) decline in the spine. We evaluated the association of current and former smoking with BMD decline after 3-year follow-up. Male current and former smokers participating in a lung cancer screening trial who underwent baseline and 3-year follow-up CT were included. BMD was measured by manual placement of a region of interest in the first lumbar vertebra and expressed in Hounsfield Unit (HU). Multiple linear regression analysis was used to evaluate the association between pack years smoked and smoking status with BMD decline. 408 participants were included with median (25th-75th percentile) age of 59.4 (55.9-63.5) years. At the start of the study, 197 (48.3%) participants were current smokers and 211 (51.7%) were former smokers and had a similar amount of pack years. Current smokers had quit smoking for 6 (4-8) years prior to inclusion. There was no difference in BMD between current and former smokers at baseline (109±34 HU vs. 108±32 HU, p=0.96). At 3-year follow-up, current smokers had a mean BMD decline of -3±13 HU (p=0.001), while BMD in former smokers did not change as compared to baseline (1±13 HU, p=0.34). After adjustment for BMD at baseline and body mass index, current smoking was independently associated with BMD decline (-3.8 HU, p=0.003). Age, pack years, and the presence of a fracture at baseline did not associate with BMD decline. Current smokers showed a more rapid BMD decline over a 3-year period compared to former smokers. This information might be important to identify subjects at risk for osteoporosis and emphasizes the importance of smoking cessation in light of BMD decline. Copyright © 2017 Elsevier B.V. All rights reserved.

MO-F-CAMPUS-J-04: Tissue Segmentation-Based MR Electron Density Mapping Method for MR-Only Radiation Treatment Planning of Brain

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yu, H; Lee, Y; Ruschin, M

2015-06-15

Purpose: Automatically derive electron density of tissues using MR images and generate a pseudo-CT for MR-only treatment planning of brain tumours. Methods: 20 stereotactic radiosurgery (SRS) patients’ T1-weighted MR images and CT images were retrospectively acquired. First, a semi-automated tissue segmentation algorithm was developed to differentiate tissues with similar MR intensities and large differences in electron densities. The method started with approximately 12 slices of manually contoured spatial regions containing sinuses and airways, then air, bone, brain, cerebrospinal fluid (CSF) and eyes were automatically segmented using edge detection and anatomical information including location, shape, tissue uniformity and relative intensity distribution.more » Next, soft tissues - muscle and fat were segmented based on their relative intensity histogram. Finally, intensities of voxels in each segmented tissue were mapped into their electron density range to generate pseudo-CT by linearly fitting their relative intensity histograms. Co-registered CT was used as a ground truth. The bone segmentations of pseudo-CT were compared with those of co-registered CT obtained by using a 300HU threshold. The average distances between voxels on external edges of the skull of pseudo-CT and CT in three axial, coronal and sagittal slices with the largest width of skull were calculated. The mean absolute electron density (in Hounsfield unit) difference of voxels in each segmented tissues was calculated. Results: The average of distances between voxels on external skull from pseudo-CT and CT were 0.6±1.1mm (mean±1SD). The mean absolute electron density differences for bone, brain, CSF, muscle and fat are 78±114 HU, and 21±8 HU, 14±29 HU, 57±37 HU, and 31±63 HU, respectively. Conclusion: The semi-automated MR electron density mapping technique was developed using T1-weighted MR images. The generated pseudo-CT is comparable to that of CT in terms of anatomical position of tissues and similarity of electron density assignment. This method can allow MR-only treatment planning.« less

Folate receptor-targeted nanoparticle delivery of HuR-RNAi suppresses lung cancer cell proliferation and migration.

PubMed

Muralidharan, Ranganayaki; Babu, Anish; Amreddy, Narsireddy; Basalingappa, Kanthesh; Mehta, Meghna; Chen, Allshine; Zhao, Yan Daniel; Kompella, Uday B; Munshi, Anupama; Ramesh, Rajagopal

2016-06-21

Human antigen R (HuR) is an RNA binding protein that is overexpressed in many human cancers, including lung cancer, and has been shown to regulate the expression of several oncoproteins. Further, HuR overexpression in cancer cells has been associated with poor-prognosis and therapy resistance. Therefore, we hypothesized that targeted inhibition of HuR in cancer cells should suppress several HuR-regulated oncoproteins resulting in an effective anticancer efficacy. To test our hypothesis, in the present study we investigated the efficacy of folate receptor-α (FRA)-targeted DOTAP:Cholesterol lipid nanoparticles carrying HuR siRNA (HuR-FNP) against human lung cancer cells. The therapeutic efficacy of HuR-FNP was tested in FRA overexpressing human H1299 lung cancer cell line and compared to normal lung fibroblast (CCD16) cells that had low to no FRA expression. Physico-chemical characterization studies showed HuR-FNP particle size was 303.3 nm in diameter and had a positive surface charge (+4.3 mV). Gel retardation and serum stability assays showed that the FNPs were efficiently protected siRNA from rapid degradation. FNP uptake was significantly higher in H1299 cells compared to CCD16 cells indicating a receptor-dose effect. The results of competitive inhibition studies in H1299 cells demonstrated that HuR-FNPs were efficiently internalized via FRA-mediated endocytosis. Biologic studies demonstrated HuR-FNP but not C-FNP (control siRNA) induced G1 phase cell-cycle arrest and apoptosis in H1299 cells resulting in significant growth inhibition. Further, HuR-FNP exhibited significantly higher cytotoxicity against H1299 cells than it did against CCD16 cells. The reduction in H1299 cell viability was correlated with a marked decrease in HuR mRNA and protein expression. Further, reduced expression of HuR-regulated oncoproteins (cyclin D1, cyclin E, and Bcl-2) and increased p27 tumor suppressor protein were observed in HuR-FNP-treated H1299 cells but not in C-FNP-treated cells. Finally, cell migration was significantly inhibited in HuR-FNP-treated H1299 cells compared to C-FNP. Our results demonstrate that HuR is a molecular target for lung cancer therapy and its suppression using HuR-FNP produced significant therapeutic efficacy in vitro.

The novel antihyperglycaemic action of Hunteria umbellata seed fractions mediated via intestinal glucose uptake inhibition.

PubMed

Adeneye, A A; Adeyemi, O O; Agbaje, E O; Sofidiya, M O

2012-01-01

The present study evaluated the antihyperglycaemic effect and mechanism of action of fractions of the aqueous seed extract of Hunteria umbellata (K. Schum.) Hallier f. (HU) in normal and alloxan-induced hyperglycaemic rats. HU was partitioned in chloroform, acetyl acetate and butan-1-ol to give chloroform fraction (HU c), ethyl acetate fraction (HU e), butanol fraction (HU b) and the "residue" (HU m), respectively. 200 mg/kg of each of these fraction dissolved in 5% Tween 20 in distilled water was investigated for its acute oral hypoglycaemic effects in normal rats over 6 hours while its repeated dose antihyperglycaemic effect was evaluated in alloxan-induced hyperglycaemic rats over 5 days. In addition, 50 mg/kg of the crude alkaloid fraction (HU Af) extracted from HU was evaluated for its possible antihyperglycaemic activity in alloxaninduced hyperglycaemic rats using oral glucose tolerance test (OGTT) over 6 hours. Using the solvent system, distilled water-butanol-ammonium hydroxide (2:15:1, v/v/v), HU b was chromatographed and stained with Dragendorff's reagent for confirmatory qualitative analysis for alkaloids. Results showed that oral pre-treatment with 200 mg/kg of HU e, HU b and HU m resulted in a significant (p<0.05, p<0.001) time dependent hypoglycaemic effect, with the butan-1-ol fraction HU causing the most significant (p<0.001) hypoglycaemic effect. In the alloxan-induced hyperglycaemic rats, repeated oral treatment with 200 mg/kg of same HU fractions for 5 days resulted in significant (p<0.05) decreases in the fasting blood glucose concentrations with the most significant (p<0.01) antihyperglycaemic effect also recorded for HU b. Similarly, oral pretreatment with 50 mg/kg of HU Af significantly (p<0.05, p<0.01 and p<0.001) attenuated an increase in the post-absorptive glucose concentration at 1(st) - 6(th) h in the alloxan-induced hyperglycaemic OGTT model. In addition, alkaloid was present in most of the separated spots on the TLC plate. In conclusion, results of this study showed that HU contains a relative high amount of alkaloids which could have accounted for the antihyperglycaemic action of HU that was mediated via intestinal glucose uptake inhibition.

Value of two-phase dynamic multidetector computed tomography in differential diagnosis of post-inflammatory strictures from esophageal cancer

PubMed Central

Karmazanovsky, Grigory G; Buryakina, Svetlana A; Kondratiev, Evgeny V; Yang, Qin; Ruchkin, Dmitry V; Kalinin, Dmitry V

2015-01-01

AIM: To characterize the computed tomography (CT) findings in patients with post-inflammatory esophageal strictures (corrosive and peptic) and reveal the optimal scanning phase protocols for distinguishing post-inflammatory esophageal stricture and esophageal cancer. METHODS: Sixty-five patients with esophageal strictures of different etiology were included in this study: 24 patients with 27 histopathologically confirmed corrosive strictures, 10 patients with 12 peptic strictures and 31 patients with esophageal cancer were evaluated with a two-phase dynamic contrast-enhanced MDCT. Arterial and venous phases at 10 and 35 s after the attenuation of 200 HU were obtained at the descending aorta, with a delayed phase at 6-8 min after the start of injection of contrast media. For qualitative analysis, CT scans of benign strictures were reviewed for the presence/absence of the following features: “target sign”, luminal mass, homogeneity of contrast medium uptake, concentric wall thickening, conically shaped suprastenotic dilatation, smooth boundaries of stenosis and smooth mucous membrane at the transition to stenosis, which were compared with a control group of 31 patients who had esophageal cancer. The quantitative analysis included densitometric parameter acquisition using regions-of-interest measurement of the zone of stenosis and normal esophageal wall and the difference between those measurements (ΔCT) at all phases of bolus contrast enhancement. Esophageal wall thickening, length of esophageal wall thickening and size of the regional lymph nodes were also evaluated. RESULTS: The presence of a concentric esophageal wall, conically shaped suprastenotic dilatation, smooth upper and lower boundaries, “target sign” and smooth mucous membrane at the transition to stenosis were suggestive of a benign cause, with sensitivities of 92.31%, 87.17%, 94.87%, 76.92% and 82.05%, respectively, and specificities of 70.96%, 89.66%, 80.65%, 96.77% and 93.55%, respectively. The features that were most suggestive of a malignant cause were eccentric esophageal wall thickening, tuberous upper and lower boundaries of stenosis, absence of mucous membrane visualization, rupture of the mucous membrane at the upper boundary of stenosis, cup-shaped suprastenotic dilatation, luminal mass and enlarged regional lymph nodes with specificities of 92.31% 94.87%, 67.86%, 100%, 97.44%, 94.87% and 82.86%, respectively and sensitivities of 70.97%, 80.65%, 96.77%, 80.65%, 54.84%, 87.10% and 60%, respectively. The highest tumor attenuation occurred in the arterial phase (mean attenuation 74.13 ± 17.42 HU), and the mean attenuation difference between the tumor and the normal esophageal wall (mean ΔCT) in the arterial phase was 23.86 ± 19.31 HU. Here, 11.5 HU of ΔCT in the arterial phase was the cut-off value used to differentiate esophageal cancer from post-inflammatory stricture (P = 0.000). The highest attenuation of post-inflammatory strictures occurred in the delayed phase (mean attenuation 71.66 ± 14.28 HU), and the mean ΔCT in delayed phase was 34.03 ± 15.94 HU. Here, 18.5 HU of ΔCT in delayed phase was the cut-off value used to differentiate post-inflammatory stricture from esophageal cancer (P < 0.0001). CONCLUSION: The described imaging findings reveal high diagnostic significance in the differentiation of benign strictures from esophageal cancer. PMID:26269677

Identification and Validation of Novel Small Molecule Disruptors of HuR-mRNA Interaction

PubMed Central

Wu, Xiaoqing; Lan, Lan; Wilson, David Michael; Marquez, Rebecca T.; Tsao, Wei-chung; Gao, Philip; Roy, Anuradha; Turner, Benjamin Andrew; McDonald, Peter; Tunge, Jon A; Rogers, Steven A; Dixon, Dan A.; Aubé, Jeffrey; Xu, Liang

2015-01-01

HuR, an RNA binding protein, binds to adenine- and uridine-rich elements (ARE) in the 3′-untranslated region (UTR) of target mRNAs, regulating their stability and translation. HuR is highly abundant in many types of cancer, and it promotes tumorigenesis by interacting with cancer-associated mRNAs, which encode proteins that are implicated in different tumor processes including cell proliferation, cell survival, angiogenesis, invasion, and metastasis. Drugs that disrupt the stabilizing effect of HuR upon mRNA targets could have dramatic effects on inhibiting cancer growth and persistence. In order to identify small molecules that directly disrupt the HuR–ARE interaction, we established a fluorescence polarization (FP) assay optimized for high throughput screening (HTS) using HuR protein and an ARE oligo from Musashi RNA-binding protein 1 (Msi1) mRNA, a HuR target. Following the performance of an HTS of ~6000 compounds, we discovered a cluster of potential disruptors, which were then validated by AlphaLISA (Amplified Luminescent Proximity Homogeneous Assay), surface plasmon resonance (SPR), ribonucleoprotein immunoprecipitation (RNP IP) assay, and luciferase reporter functional studies. These compounds disrupted HuR–ARE interactions at the nanomolar level and blocked HuR function by competitive binding to HuR. These results support future studies toward chemical probes for a HuR function study and possibly a novel therapy for HuR-overexpressing cancers. PMID:25750985

Overexpression of Neuronal RNA-binding protein HuD increases reward induced reinstatement of an instrumental response.

PubMed

Oliver, Robert J; Kenton, Johnny A; Stevens, Wennonah; Perrone-Bizzozero, Nora I; Brigman, Jonathan L

2018-06-22

The neuronal RNA-binding protein HuD is involved in synaptic plasticity and the molecular mechanisms of learning and memory. Previously, we have shown that HuD is upregulated after both spatial and addiction-associated forms of learning, such as conditioned place preference. However, what role HuD plays in non-drug dependent learning and memory is not fully understood. In order to elucidate the role that HuD plays in non-drug appetitive behavior, we assessed mice over-expressing HuD (HuD OE ) throughout the forebrain on the acquisition of an instrumental response for a non-sucrose food reward utilizing a touch-screen paradigm. Next, we examined whether HuD level would alter the extinction or reward-induced reinstatement of responding. We found that HuD OE acquired and extinguished the instrumental response at rates similar to control littermates with no significant alterations in secondary measures of motor behavior or motivation. However, HuD OE reinstated their responding for food reward at rates significantly higher than control animals after a brief presentation of reward. These results suggest that HuD positively regulates the reinstatement of natural reward seeking and supports the role of HuD in forms of learning and memory associated with seeking of appetitive rewards. Copyright © 2018. Published by Elsevier B.V.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kim, Inae; Hur, Jung; Jeong, Sunjoo, E-mail: sjsj@dankook.ac.kr

Highlights: • Wnt signaling as well as β-catenin overexpression enhance HuR cytoplasmic export. • HuR overexpression promotes cytoplasmic localization of β-catenin from the perinuclear fraction. • Wnt/β-catenin-mediated transcriptional activity is repressesed by HuR. - Abstract: β-Catenin is the key transcriptional activator of canonical Wnt signaling in the nucleus; thus, nuclear accumulation of β-catenin is a critical step for expressing target genes. β-Catenin accumulates in the nucleus of cancer cells where it activates oncogenic target genes. Hu antigen R (HuR) is a RNA binding protein that regulates multiple post-transcriptional processes including RNA stability. Thus, cytoplasmic HuR protein may be involved inmore » tumorigenesis by stabilizing oncogenic transcripts, but the molecular mechanism remains unclear. Here, we observed that Wnt/β-catenin signaling induced export of the HuR protein, whereas HuR overexpression promoted accumulation of the β-catenin protein in the cytoplasm. Thus, Wnt/β-catenin-mediated transcriptional activity in the nucleus was reduced by overexpressing HuR. These results suggest novel and uncharacterized cytoplasmic β-catenin functions related to HuR-mediated RNA metabolism in cancer cells.« less

Dosimetric Evaluation of Metal Artefact Reduction using Metal Artefact Reduction (MAR) Algorithm and Dual-energy Computed Tomography (CT) Method

NASA Astrophysics Data System (ADS)

Laguda, Edcer Jerecho

Purpose: Computed Tomography (CT) is one of the standard diagnostic imaging modalities for the evaluation of a patient's medical condition. In comparison to other imaging modalities such as Magnetic Resonance Imaging (MRI), CT is a fast acquisition imaging device with higher spatial resolution and higher contrast-to-noise ratio (CNR) for bony structures. CT images are presented through a gray scale of independent values in Hounsfield units (HU). High HU-valued materials represent higher density. High density materials, such as metal, tend to erroneously increase the HU values around it due to reconstruction software limitations. This problem of increased HU values due to metal presence is referred to as metal artefacts. Hip prostheses, dental fillings, aneurysm clips, and spinal clips are a few examples of metal objects that are of clinical relevance. These implants create artefacts such as beam hardening and photon starvation that distort CT images and degrade image quality. This is of great significance because the distortions may cause improper evaluation of images and inaccurate dose calculation in the treatment planning system. Different algorithms are being developed to reduce these artefacts for better image quality for both diagnostic and therapeutic purposes. However, very limited information is available about the effect of artefact correction on dose calculation accuracy. This research study evaluates the dosimetric effect of metal artefact reduction algorithms on severe artefacts on CT images. This study uses Gemstone Spectral Imaging (GSI)-based MAR algorithm, projection-based Metal Artefact Reduction (MAR) algorithm, and the Dual-Energy method. Materials and Methods: The Gemstone Spectral Imaging (GSI)-based and SMART Metal Artefact Reduction (MAR) algorithms are metal artefact reduction protocols embedded in two different CT scanner models by General Electric (GE), and the Dual-Energy Imaging Method was developed at Duke University. All three approaches were applied in this research for dosimetric evaluation on CT images with severe metal artefacts. The first part of the research used a water phantom with four iodine syringes. Two sets of plans, multi-arc plans and single-arc plans, using the Volumetric Modulated Arc therapy (VMAT) technique were designed to avoid or minimize influences from high-density objects. The second part of the research used projection-based MAR Algorithm and the Dual-Energy Method. Calculated Doses (Mean, Minimum, and Maximum Doses) to the planning treatment volume (PTV) were compared and homogeneity index (HI) calculated. Results: (1) Without the GSI-based MAR application, a percent error between mean dose and the absolute dose ranging from 3.4-5.7% per fraction was observed. In contrast, the error was decreased to a range of 0.09-2.3% per fraction with the GSI-based MAR algorithm. There was a percent difference ranging from 1.7-4.2% per fraction between with and without using the GSI-based MAR algorithm. (2) A range of 0.1-3.2% difference was observed for the maximum dose values, 1.5-10.4% for minimum dose difference, and 1.4-1.7% difference on the mean doses. Homogeneity indexes (HI) ranging from 0.068-0.065 for dual-energy method and 0.063-0.141 with projection-based MAR algorithm were also calculated. Conclusion: (1) Percent error without using the GSI-based MAR algorithm may deviate as high as 5.7%. This error invalidates the goal of Radiation Therapy to provide a more precise treatment. Thus, GSI-based MAR algorithm was desirable due to its better dose calculation accuracy. (2) Based on direct numerical observation, there was no apparent deviation between the mean doses of different techniques but deviation was evident on the maximum and minimum doses. The HI for the dual-energy method almost achieved the desirable null values. In conclusion, the Dual-Energy method gave better dose calculation accuracy to the planning treatment volume (PTV) for images with metal artefacts than with or without GE MAR Algorithm.

Antidepressant-like actions by silencing of neuronal ELAV-like RNA-binding proteins HuB and HuC in a model of depression in male mice.

PubMed

Sanna, Maria Domenica; Quattrone, Alessandro; Galeotti, Nicoletta

2018-06-01

Currently available antidepressant drugs often fail to achieve full remission and patients might evolve to treatment resistance, showing the need to achieve a better therapy of depressive disorders. Increasing evidence supports that post-transcriptional regulation of gene expression is important in neuronal development and survival and a relevant role is played by RNA binding proteins (RBP). To explore new therapeutic strategies, we investigated the role of the neuron-specific ELAV-like RBP (HuB, HuC, HuD) in a mouse model of depression. In this study, a 4-week unpredictable chronic mild stress (UCMS) protocol was applied to mice to induce a depressive-like phenotype. In the last 2 weeks of the UCMS regimen, silencing of HuB, HuC or HuD was performed by using specific antisense oligonucleotides (aODN). Treatment of UCMS-exposed mice with anti-HuB and anti-HuC aODN improved both anhedonia and behavioural despair, used as measures of depressive-like behaviour, without modifying the response of stressed mice to an anxiety-inducing environment. On the contrary, HuD silencing promoted an anxiolytic-like behaviour in UCMS-exposed mice without improving depressive-like behaviours. The antidepressant-like phenotype of anti-HuB and anti-HuC mice was not shown concurrently with the promotion of adult hippocampal neurogenesis in the dentate gyrus, and no increase in the BDNF and CREB content was detected. Conversely, in the CA3 hippocampal region, projection area of newly born neurons, HuB and HuC silencing increased the number of BrdU/NeuN positive cells. These results give the first indication of a role of nELAV in the modulation of emotional states in a mouse model of depression. Copyright © 2018 Elsevier Ltd. All rights reserved.

The mRNA-stabilizing factor HuR protein is targeted by β-TrCP protein for degradation in response to glycolysis inhibition.

PubMed

Chu, Po-Chen; Chuang, Hsiao-Ching; Kulp, Samuel K; Chen, Ching-Shih

2012-12-21

The mRNA-stabilizing protein HuR acts a stress response protein whose function and/or protein stability are modulated by diverse stress stimuli through posttranslational modifications. Here, we report a novel mechanism by which metabolic stress facilitates proteasomal degradation of HuR in cancer cells. In response to the glucose transporter inhibitor CG-5, HuR translocates to the cytoplasm, where it is targeted by the ubiquitin E3 ligase β-TrCP1 for degradation. The cytoplasmic localization of HuR is facilitated by PKCα-mediated phosphorylation at Ser-318 as the Ser-318 → alanine substitution abolishes the ability of the resulting HuR to bind PKCα and to undergo nuclear export. The mechanistic link between β-TrCP1 and HuR degradation was supported by the ability of ectopically expressed β-TrCP1 to mimic CG-5 to promote HuR degradation and by the protective effect of dominant negative inhibition of β-TrCP1 on HuR ubiquitination and degradation. Substrate targeting of HuR by β-TrCP1 was further verified by coimmunoprecipitation and in vitro GST pull-down assays and by the identification of a β-TrCP1 recognition site. Although HuR does not contain a DSG destruction motif, we obtained evidence that β-TrCP1 recognizes an unconventional motif, (296)EEAMAIAS(304), in the RNA recognition motif 3. Furthermore, mutational analysis indicates that IKKα-dependent phosphorylation at Ser-304 is crucial to the binding of HuR to β-TrCP1. Mechanistically, this HuR degradation pathway differs from that reported for heat shock and hypoxia, which underlies the complexity in the regulation of HuR turnover under different stress stimuli. The ability of glycolysis inhibitors to target the expression of oncogenic proteins through HuR degradation might foster novel strategies for cancer therapy.

The mRNA-stabilizing Factor HuR Protein Is Targeted by β-TrCP Protein for Degradation in Response to Glycolysis Inhibition*

PubMed Central

Chu, Po-Chen; Chuang, Hsiao-Ching; Kulp, Samuel K.; Chen, Ching-Shih

2012-01-01

The mRNA-stabilizing protein HuR acts a stress response protein whose function and/or protein stability are modulated by diverse stress stimuli through posttranslational modifications. Here, we report a novel mechanism by which metabolic stress facilitates proteasomal degradation of HuR in cancer cells. In response to the glucose transporter inhibitor CG-5, HuR translocates to the cytoplasm, where it is targeted by the ubiquitin E3 ligase β-TrCP1 for degradation. The cytoplasmic localization of HuR is facilitated by PKCα-mediated phosphorylation at Ser-318 as the Ser-318 → alanine substitution abolishes the ability of the resulting HuR to bind PKCα and to undergo nuclear export. The mechanistic link between β-TrCP1 and HuR degradation was supported by the ability of ectopically expressed β-TrCP1 to mimic CG-5 to promote HuR degradation and by the protective effect of dominant negative inhibition of β-TrCP1 on HuR ubiquitination and degradation. Substrate targeting of HuR by β-TrCP1 was further verified by coimmunoprecipitation and in vitro GST pull-down assays and by the identification of a β-TrCP1 recognition site. Although HuR does not contain a DSG destruction motif, we obtained evidence that β-TrCP1 recognizes an unconventional motif, 296EEAMAIAS304, in the RNA recognition motif 3. Furthermore, mutational analysis indicates that IKKα-dependent phosphorylation at Ser-304 is crucial to the binding of HuR to β-TrCP1. Mechanistically, this HuR degradation pathway differs from that reported for heat shock and hypoxia, which underlies the complexity in the regulation of HuR turnover under different stress stimuli. The ability of glycolysis inhibitors to target the expression of oncogenic proteins through HuR degradation might foster novel strategies for cancer therapy. PMID:23115237

Preliminary study on the diagnostic value of single-source dual-energy CT in diagnosing cervical lymph node metastasis of thyroid carcinoma

PubMed Central

Zhao, Yanfeng; Li, Xiaolu; Wang, Xiaoyi; Lin, Meng; Zhao, Xinming; Luo, Dehong; Li, Jianying

2017-01-01

Background To investigate the value of single-source dual-energy spectral CT imaging in improving the accuracy of preoperative diagnosis of lymph node metastasis of thyroid carcinoma. Methods Thirty-four thyroid carcinoma patients were enrolled and received spectral CT scanning before thyroidectomy and cervical lymph node dissection surgery. Iodine-based material decomposition (MD) images and 101 sets of monochromatic images from 40 to 140 keV were reconstructed after CT scans. The iodine concentrations (IC) of lymph nodes were measured on the MD images and was normalized to that of common carotid artery to obtain the normalized iodine concentration (NIC). The CT number of lymph nodes as function of photon energy was measured on the 101 sets of images to generate a spectral HU curve and to calculate its slope λHU. The measurements between the metastatic and non-metastatic lymph nodes were statistically compared and receiver operating characteristic (ROC) curves were used to determine the optimal thresholds of these measurements for diagnosing lymph nodes metastasis. Results There were 136 lymph nodes that were pathologically confirmed. Among them, 102 (75%) were metastatic and 34 (25%) were non-metastatic. The IC, NIC and the slope λHU of the metastatic lymph nodes were 3.93±1.58 mg/mL, 0.70±0.55 and 4.63±1.91, respectively. These values were statistically higher than the respective values of 1.77±0.71 mg/mL, 0.29±0.16 and 2.19±0.91 for the non-metastatic lymph nodes (all P<0.001). ROC analysis determined the optimal diagnostic threshold for IC as 2.56 mg/mL, with the sensitivity, specificity and accuracy of 83.3%, 91.2% and 85.3%, respectively. The optimal threshold for NIC was 0.289, with the sensitivity, specificity and accuracy of 96.1%, 76.5% and 91.2%, respectively. The optimal threshold for the spectral curve slope λHU was 2.692, with the sensitivity, specificity and accuracy of 88.2%, 82.4% and 86.8%, respectively. Conclusions The measurements obtained in dual-energy spectral CT improve the sensitivity and accuracy for preoperatively diagnosing lymph node metastasis in thyroid carcinoma. PMID:29268547

Development and validation of segmentation and interpolation techniques in sinograms for metal artifact suppression in CT.

PubMed

Veldkamp, Wouter J H; Joemai, Raoul M S; van der Molen, Aart J; Geleijns, Jacob

2010-02-01

Metal prostheses cause artifacts in computed tomography (CT) images. The purpose of this work was to design an efficient and accurate metal segmentation in raw data to achieve artifact suppression and to improve CT image quality for patients with metal hip or shoulder prostheses. The artifact suppression technique incorporates two steps: metal object segmentation in raw data and replacement of the segmented region by new values using an interpolation scheme, followed by addition of the scaled metal signal intensity. Segmentation of metal is performed directly in sinograms, making it efficient and different from current methods that perform segmentation in reconstructed images in combination with Radon transformations. Metal signal segmentation is achieved by using a Markov random field model (MRF). Three interpolation methods are applied and investigated. To provide a proof of concept, CT data of five patients with metal implants were included in the study, as well as CT data of a PMMA phantom with Teflon, PVC, and titanium inserts. Accuracy was determined quantitatively by comparing mean Hounsfield (HU) values and standard deviation (SD) as a measure of distortion in phantom images with titanium (original and suppressed) and without titanium insert. Qualitative improvement was assessed by comparing uncorrected clinical images with artifact suppressed images. Artifacts in CT data of a phantom and five patients were automatically suppressed. The general visibility of structures clearly improved. In phantom images, the technique showed reduced SD close to the SD for the case where titanium was not inserted, indicating improved image quality. HU values in corrected images were different from expected values for all interpolation methods. Subtle differences between interpolation methods were found. The new artifact suppression design is efficient, for instance, in terms of preserving spatial resolution, as it is applied directly to original raw data. It successfully reduced artifacts in CT images of five patients and in phantom images. Sophisticated interpolation methods are needed to obtain reliable HU values close to the prosthesis.

Accuracy of iodine removal using dual-energy CT with or without a tin filter: an experimental phantom study.

PubMed

Kawai, Tatsuya; Takeuchi, Mitsuru; Hara, Masaki; Ohashi, Kazuya; Suzuki, Hirochika; Yamada, Kiyotaka; Sugimura, Yuya; Shibamoto, Yuta

2013-10-01

The effects of a tin filter on virtual non-enhanced (VNE) images created by dual-energy CT have not been well evaluated. To compare the accuracy of VNE images between those with and without a tin filter. Two different types of columnar phantoms made of agarose gel were evaluated. Phantom A contained various concentrations of iodine (4.5-1590 HU at 120 kVp). Phantom B consisted of a central component (0, 10, 25, and 40 mgI/cm(3)) and a surrounding component (0, 50, 100, and 200 mgI/cm(3)) with variable iodine concentration. They were scanned by dual-source CT in conventional single-energy mode and dual-energy mode with and without a tin filter. CT values on each gel at the corresponding points were measured and the accuracy of iodine removal was evaluated. On VNE images, the CT number of the gel of Phantom A fell within the range between -15 and +15 HU under 626 and 881 HU at single-energy 120 kVp with and without a tin filter, respectively. With attenuation over these thresholds, iodine concentration of gels was underestimated with the tin filter but overestimated without it. For Phantom B, the mean CT numbers on VNE images in the central gel component surrounded by the gel with iodine concentrations of 0, 50, 100, and 200 mgI/cm(3) were in the range of -19-+6 HU and 21-100 HU with and without the tin filter, respectively. Both with and without a tin filter, iodine removal was accurate under a threshold of iodine concentration. Although a surrounding structure with higher attenuation decreased the accuracy, a tin filter improved the margin of error.

HU-446 and HU-465, Derivatives of the Non-psychoactive Cannabinoid Cannabidiol, Decrease the Activation of Encephalitogenic T Cells.

PubMed

Kozela, Ewa; Haj, Christeene; Hanuš, Lumir; Chourasia, Mukesh; Shurki, Avital; Juknat, Ana; Kaushansky, Nathali; Mechoulam, Raphael; Vogel, Zvi

2016-01-01

Cannabidiol (CBD), the non-psychoactive cannabinoid, has been previously shown by us to decrease peripheral inflammation and neuroinflammation in mouse experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis (MS). Here we have studied the anti-inflammatory effects of newly synthesized derivatives of natural (-)-CBD ((-)-8,9-dihydro-7-hydroxy-CBD; HU-446) and of synthetic (+)-CBD ((+)-8,9-dihydro-7-hydroxy-CBD; HU-465) on activated myelin oligodendrocyte glycoprotein (MOG)35-55-specific mouse encephalitogenic T cells (T(MOG) ) driving EAE/MS-like pathologies. Binding assays followed by molecular modeling revealed that HU-446 has negligible affinity toward the cannabinoid CB1 and CB2 receptors while HU-465 binds to both CB1 and CB2 receptors at the high nanomolar concentrations (Ki = 76.7 ± 5.8 nm and 12.1 ± 2.3 nm, respectively). Both, HU-446 and HU-465, at 5 and 10 μm (but not at 0.1 and 1 μm), inhibited the MOG35-55-induced proliferation of autoreactive T(MOG) cells via CB1/CB2 receptor independent mechanisms. Moreover, both HU-446 and HU-465, at 5 and 10 μm, inhibited the release of IL-17, a key autoimmune cytokine, from MOG35-55-stimulated T(MOG) cells. These results suggest that HU-446 and HU-465 have anti-inflammatory potential in inflammatory and autoimmune diseases. © 2015 John Wiley & Sons A/S.

TU-F-CAMPUS-J-04: Evaluation of Metal Artifact Reduction Technique for the Radiation Therapy Planning

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jeong, K; Kuo, H; Ritter, J

Purpose: To evaluate the feasibility of using a metal artifact reduction technique in depleting metal artifact and its application in improving dose calculation in External Radiation Therapy Planning. Methods: CIRS electron density phantom was scanned with and without steel drill bits placed in some plug holes. Meta artifact reduction software with Metal Deletion Technique (MDT) was used to remove metal artifacts for scanned image with metal. Hounsfield units of electron density plugs from artifact free reference image and MDT processed images were compared. To test the dose calculation improvement after the MDT processed images, clinically approved head and neck planmore » with manual dental artifact correction was tested. Patient images were exported and processed with MDT and plan was recalculated with new MDT image without manual correction. Dose profiles near the metal artifacts were compared. Results: The MDT used in this study effectively reduced the metal artifact caused by beam hardening and scatter. The windmill around the metal drill was greatly improved with smooth rounded view. Difference of the mean HU in each density plug between reference and MDT images were less than 10 HU in most of the plugs. Dose difference between original plan and MDT images were minimal. Conclusion: Most metal artifact reduction methods were developed for diagnostic improvement purpose. Hence Hounsfield unit accuracy was not rigorously tested before. In our test, MDT effectively eliminated metal artifacts with good HU reproduciblity. However, it can introduce new mild artifacts so the MDT images should be checked with original images.« less

The Economic Effects of the President’s 2015 Budget

DTIC Science & Technology

2014-07-01

CONGRESS OF THE UNITED STATES CONGRESSIONAL BUDGET OFFICE CBO The Economic Effects of the President’s 2015 Budget JULY 2014 © S hu tte rs to ck...from other proposals: cuts in spending for overseas military operations, reductions in Medicare’s net payments, and tax increases for people with high

Evaluation of variations in absorbed dose and image noise according to patient forms in X-ray computed tomography.

PubMed

Matsubara, Kosuke; Koshida, Kichiro; Suzuki, Masayuki; Hayakawa, Mayumi; Tsujii, Hideo; Yamamoto, Tomoyuki

2005-12-20

Excessive radiation exposure in pediatric computed tomography (CT) scanning has become a serious problem, and it is difficult to select scan parameters for the scanning of small patients such as children. We investigated differences in absorbed dose and standard deviation (SD) in Hounsfield unit (HU) caused by differences in the form of the subject using a body-type phantom with removable body parts. Using four X-ray CT scanners, measurements were made with values from 50 mAs to 300 mAs, with slices of 50 mAs, using scan protocols that were assumed to perform thorough examinations. The results showed that the mAs values and absorbed doses were almost proportional, and the absorbed doses in the phantom without body parts were about 1.1-2.2-fold higher than those of the phantom with body parts at the same points. The SD values obtained indicated that the absorbed doses in the phantom with body parts were 0.3-0.6 times those of the phantom without body parts when the mAs values used were adjusted so that both SD values were the same. The absorbed doses in various patient forms can be estimated from these results, and they will become critical data for the selection of appropriate scan protocols.

Evaluation of prosthetic valve obstruction on electrocardiographically gated multidetector-row computed tomography--identification of subprosthetic pannus in the aortic position.

PubMed

Ueda, Tomohiro; Teshima, Hideki; Fukunaga, Shuji; Aoyagi, Shigeaki; Tanaka, Hiroyuki

2013-01-01

This study was performed to evaluate the diagnostic role of electrocardiographically gated multidetector-row computed tomography (MDCT) for prosthetic valve obstruction (PVO) in the aortic position. Between 2002 and 2006, 9 patients were diagnosed with PVO of an aortic bileaflet mechanical valve based on echocardiographic and cineradiographic criteria. These 9 patients were examined using MDCT before replacement of the mechanical valve, and intraoperative findings were compared to morphologic periprosthetic abnormalities observed on MDCT. CT attenuation (Hounsfield units; HU) of the periprosthetic abnormalities was measured to investigate the underlying cause of the PVO. MDCT showed subprosthetic masses extending beyond the prosthetic ring into the orifice of the valve. At reoperation, presence of subprosthetic pannus was confirmed in all of the 9 patients, but no periprosthetic thrombus was found. The mean CT attenuation of the subprosthetic pannus was 170 HU, and it was significantly greater than that obtained from the interventricular septum (108 HU; P<0.0001). MDCT can be used to clearly visualize subprosthetic pannus causing PVO and the mean CT attenuation of subprosthetic pannus is significantly higher than that of the interventricular septum on MDCT.

Cytoplasmic Hu-Antigen R (HuR) Expression is Associated with Poor Survival in Patients with Surgically Resected Cholangiocarcinoma Treated with Adjuvant Gemcitabine-Based Chemotherapy.

PubMed

Toyota, Kazuhiro; Murakami, Yoshiaki; Kondo, Naru; Uemura, Kenichiro; Nakagawa, Naoya; Takahashi, Shinya; Sueda, Taijiro

2018-05-01

Hu-antigen R (HuR) is an RNA-binding protein that regulates the stability, translation, and nucleus-to-cytoplasm translocation of messenger RNAs (mRNAs). The aim of this study was to investigate the prognostic significance of HuR in cholangiocarcinoma patients who received adjuvant gemcitabine-based chemotherapy (AGC) after surgical resection. Nuclear and cytoplasmic HuR expression was investigated immunohistochemically in 131 patients with resected cholangiocarcinoma, including 91 patients administered AGC and 40 patients who did not receive adjuvant chemotherapy. The correlation between HuR expression and survival was evaluated by statistical analysis. High nuclear and cytoplasmic HuR expression was observed in 67 (51%) and 45 (34%) patients, respectively. Cytoplasmic HuR expression was significantly associated with lymph node metastasis (p < 0.01), while high cytoplasmic HuR expression was significantly associated with poor disease-free survival [DFS] (p = 0.03) and overall survival [OS] (p = 0.001) in the 91 patients who received AGC, but not in the 40 patients who did not receive AGC (DFS p = 0.17; OS p = 0.07). In the multivariate analysis of patients who received AGC, high cytoplasmic HuR expression was an independent predictor of poor DFS (hazard ratio [HR] 1.77; p = 0.04) and OS (HR 2.09; p = 0.02). Nuclear HuR expression did not affect the survival of enrolled patients. High cytoplasmic HuR expression was closely associated with the efficacy of AGC in patients with cholangiocarcinoma. The current findings warrant further investigations to optimize adjuvant chemotherapy regimens for resectable cholangiocarcinoma.

FRET-detectable interactions between the ARE binding proteins, HuR and p37AUF1

PubMed Central

David, Pamela S.; Tanveer, Rasheeda; Port, J. David

2007-01-01

A number of highly regulated gene classes are regulated post-transcriptionally at the level of mRNA stability. A central feature in these mRNAs is the presence of A+U-rich elements (ARE) within their 3′ UTRs. Two ARE binding proteins, HuR and AUF1, are associated with mRNA stabilization and destabilization, respectively. Previous studies have demonstrated homomultimerization of each protein and the capacity to bind simultaneous or competitively to a single ARE. To investigate this possibility further, cell biological and biophysical approaches were undertaken. Protein–protein interaction was monitored by fluorescence resonance energy transfer (FRET) and by immunocytochemistry in live and fixed cells using fluorescently labeled CFP/YFP fusion proteins of HuR and p37AUF1. Strong nuclear FRET between HuR/HuR and AUF1/AUF1 homodimers as well as HuR/AUF1 heterodimers was observed. Treatment with the MAP kinase activator, anisomycin, which commonly stabilizes ARE-containing mRNAs, caused rapid nuclear to cytoplasmic shuttling of HuR. AUF1 also underwent shuttling, but on a longer time scale. After shuttling, HuR/HuR, AUF1/AUF1, and HuR/AUF1, FRET was also observed in the cytoplasm. In further studies, arsenite rapidly induced the formation of stress granules containing HuR and TIA-1 but not AUF1. The current studies demonstrate that two mRNA binding proteins, HuR and AUF1, are colocalized and are capable of functional interaction in both the nucleus and cytoplasm. FRET-based detection of AUF1/HuR interaction may serve as a basis of opening up new dimensions in delineating the functional interaction of mRNA binding proteins with RNA turnover. PMID:17626845

SU-D-207A-01: Female Pelvic Synthetic CT Generation Based On Joint Shape and Intensity Analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, L; Jolly, S; Cao, Y

Purpose: To develop a method for generating female pelvic synthetic CT (MRCT) images from a single MR scan and evaluate its utility in radiotherapy. Methods: Under IRB-approval, an imaging sequence (T1-VIBE-Dixon) was acquired for 10 patients. This sequence yields 3 useful image volumes of different contrast (“in-phase” T1-weighted, fat and water). A previously published pelvic bone shape model was used to generate a rough bone mask for each patient. A modified fuzzy c-means classification was performed on the multi spectral MR data, with a regularization term that utilizes the prior knowledge provided by the bone mask and addresses the intensitymore » overlap between different tissue types. A weighted sum of classification probabilities with attenuation values yielded MRCT volumes. The mean absolute error (MAE) between MRCT and real CT on various regions was calculated following deformable alignment (Velocity). Intensity modulated Treatment plans based on actual CT and MRCT were made and compared. Results: The average/standard deviation of MAE across 10 patients was 10.1/6.7 HU for muscle, 6.7/4.6 HU for fat, 136.9/53.5 HU for bony tissues under 850 HU (97% of total bone volume), 188.9/119.3 HU for bony tissues above 850 HU and 17.3/13.3 HU for intrapelvic soft tissues. Calculated doses were comparable for plans generated on CT and calculated using MRCT densities or vice versa, with differences in PTV D99% (mean/σ) of (–0.1/0.2 Gy) and (0.3/0.2 Gy), PTV D0.5cc of (–0.3/0.2 Gy) and (–0.4/1.7 Gy). OAR differences were similarly small for comparable structures, with differences in bowel V50Gy of (–0.3/0.2%) and (0.0/0.2%), femur V30Gy of (0.7/1.2%) and (0.2/1.2%), sacrum V20GY of (0.0/0.1%) and (–0.1/1.1%) and mean pelvic V20Gy of (0.0/0.1%) and (0.6/1.8%). Conclusion: MRCT based on a single imaging sequence in the female pelvis is feasible, with acceptably small variations in attenuation estimates and calculated doses to target and critical organs. Work supported by NIHR01EB016079.« less

Analysis of human reticulocyte genes reveals altered erythropoiesis: potential use to detect recombinant human erythropoietin doping.

PubMed

Varlet-Marie, Emmanuelle; Audran, Michel; Lejeune, Mireille; Bonafoux, Béatrice; Sicart, Marie-Therese; Marti, Jacques; Piquemal, David; Commes, Thérèse

2004-08-01

Enhancement of oxygen delivery to tissues is associated with improved sporting performance. One way of enhancing oxygen delivery is to take recombinant human erythropoietin (rHuEpo), which is an unethical and potentially dangerous practice. However, detection of the use of rHuEpo remains difficult in situations such as: i) several days after the end of treatment ii) when a treatment with low doses is conducted iii) if the rHuEpo effect is increased by other substances. In an attempt to detect rHuEpo abuse, we selected erythroid gene markers from a SAGE library and analyzed the effects of rHuEpo administration on expression of the HBB, FTL and OAZ genes. Ten athletes were assigned to the rHuEpo or placebo group. The rHuEpo group received subcutaneous injections of rHuEpo (50 UI/kg three times a week, 4 weeks; 20 UI/kg three times a week, 2 weeks). HBB, FTL and OAZ gene profiles were monitored by real time-polymerase chain reaction (PCR) quantification during and for 3 weeks after drug administration. The global analysis of these targeted genes detected in whole blood samples showed a characteristic profile of subjects misusing rHuEpo with a increase above the threshold levels. The individual analysis of OAZ mRNA seemed indicative of rHuEpo treatment. The performance-enhancing effect of rHuEpo treatment is greater than the duration of hematologic changes associated with rHuEpo misuse. Although direct electrophoretic methods to detect rHuEpo have been developed, recombinant isoforms of rHuEpo are not detectable some days after the last subcutaneous injection. To overcome these limitations indirect OFF models have been developed. Our data suggest that, in the near future, it will be possible to consolidate results achievable with the OFF models by analyzing selected erythroid gene markers as a supplement to indirect methods.

Accuracy of radiotherapy dose calculations based on cone-beam CT: comparison of deformable registration and image correction based methods

NASA Astrophysics Data System (ADS)

Marchant, T. E.; Joshi, K. D.; Moore, C. J.

2018-03-01

Radiotherapy dose calculations based on cone-beam CT (CBCT) images can be inaccurate due to unreliable Hounsfield units (HU) in the CBCT. Deformable image registration of planning CT images to CBCT, and direct correction of CBCT image values are two methods proposed to allow heterogeneity corrected dose calculations based on CBCT. In this paper we compare the accuracy and robustness of these two approaches. CBCT images for 44 patients were used including pelvis, lung and head & neck sites. CBCT HU were corrected using a ‘shading correction’ algorithm and via deformable registration of planning CT to CBCT using either Elastix or Niftyreg. Radiotherapy dose distributions were re-calculated with heterogeneity correction based on the corrected CBCT and several relevant dose metrics for target and OAR volumes were calculated. Accuracy of CBCT based dose metrics was determined using an ‘override ratio’ method where the ratio of the dose metric to that calculated on a bulk-density assigned version of the same image is assumed to be constant for each patient, allowing comparison to the patient’s planning CT as a gold standard. Similar performance is achieved by shading corrected CBCT and both deformable registration algorithms, with mean and standard deviation of dose metric error less than 1% for all sites studied. For lung images, use of deformed CT leads to slightly larger standard deviation of dose metric error than shading corrected CBCT with more dose metric errors greater than 2% observed (7% versus 1%).

Immunostimulatory effects of natural human interferon-alpha (huIFN-alpha) on carps Cyprinus carpio L.

PubMed

Watanuki, Hironobu; Chakraborty, Gunimala; Korenaga, Hiroki; Kono, Tomoya; Shivappa, R B; Sakai, Masahiro

2009-10-15

Human interferon-alpha (huIFN-alpha) is an important immunomodulatory substance used in the treatment and prevention of numerous infectious and immune-related diseases in animals. However, the immunostimulatory effects of huIFN-alpha in fish remain to be investigated. In the current study, the immune responses of the carp species Cyprinus carpio L. to treatment with huIFN-alpha were analyzed via measurement of superoxide anion production, phagocytic activity and the expression of cytokine genes including interleukin-1beta, tumor necrosis factor-alpha and interleukin 10. Low doses of huIFN-alpha were administered orally once a day for 3 days, and sampling was carried out at 1, 3 and 5 days post-treatment. Our results indicate that a low dose of huIFN-alpha significantly increased phagocytic activity and superoxide anion production in the carp kidney. The huIFN-alpha-treated fish also displayed a significant upregulation in cytokine gene expression. The current study demonstrates the stimulatory effects of huIFN-alpha on the carp immune system and highlights the immunomodulatory role of huIFN-alpha in fish.

Tissue distribution of mucosal antibody-producing cells specific for respiratory syncytial virus in severe combined immune deficiency (SCID) mice engrafted with human tonsils.

PubMed Central

Nadal, D; Albini, B; Schläpfer, E; Chen, C; Brodsky, L; Ogra, P L

1991-01-01

Groups of C.B-17 SCID mice were reconstituted intraperitoneally with human tonsillar mononuclear cells (hu-TMC) from children seropositive for antibody to respiratory syncytial virus (RSV) and subsequently challenged intraperitoneally with inactivated RSV or sham-immunized. The synthesis and the distribution characteristics of human antibody to RSV in various murine tissues were studied using an enzyme-linked immunospot assay (ELISPOT). No specific antibody was observed in sham-immunized animals. In contrast, mice engrafted with hu-TMC exhibited the appearance of specific human antibody secreting cells (hu-ASC) after i.p. immunization with inactivated RSV. RSV-specific hu-ASC were detected only in animals engrafted with cells from donors seropositive for antibodies to Epstein-Barr virus. Hu-TMC engrafted mice showed RSV-specific IgM and, in lower numbers, IgG hu-ASC in several tissues including the lungs. Numbers of RSV-specific IgA hu-ASC were low, however, and detected only in the lung. No RSV-specific hu-ASC were detected in the intestine. These data demonstrate for the first time that hu-TMC-SCID chimeras respond to immunization with viral antigen. Furthermore, the results suggest that hu-TMC engraft in lungs but not in the intestinal tissue. PMID:1893614

Tumor imaging using a standardized radiolabeled adapter protein docked to vascular endothelial growth factor.

PubMed

Blankenberg, Francis G; Mandl, Stefanie; Cao, Yu-An; O'Connell-Rodwell, Caitlin; Contag, Christopher; Mari, Carina; Gaynutdinov, Timur I; Vanderheyden, Jean-Luc; Backer, Marina V; Backer, Joseph M

2004-08-01

Direct radiolabeling of proteins can result in the loss of targeting activity, requires highly customized procedures, and yields heterogeneous products. Here we describe a novel imaging complex comprised of a standardized (99m)Tc-radiolabeled adapter protein noncovalently bound to a "Docking tag" fused to a "Targeting protein". The assembly of this complex is based on interactions between human 109-amino acid (HuS) and 15-amino acid (Hu-tag) fragments of ribonuclease I, which serve as an "Adapter protein" and a Docking tag, respectively. HuS modified with hydrazinonicotinamide (HYNIC) was radiolabeled using (99m)Tc-tricine to a specific activity of 3.4-7.4 MBq/microg. Protein complexes were then formed by mixing (99m)Tc-HuS with equimolar amounts of either Hu-tagged VEGF(121) (Hu-VEGF [vascular endothelial growth factor]) or Hu-tagged anti-VEGFR-2 single-chain antibody (Hu-P4G7) and incubating on ice for 15 min. 4T1 luc/gfp luciferase-expressing murine mammary adenocarcinoma cells (1 x 10(4)) were implanted subcutaneously or injected intravenously into BALB/c mice. Bioluminescent imaging (BLI) was performed 10 d later. Immediately after BLI visualization of tumor, 18.5-37 MBq of tracer (5-10 microg of protein) were injected via tail vein. One hour later planar or SPECT images were obtained, followed by killing the mice. There was significantly (P = 0.0128) increased uptake of (99m)Tc-HuS/Hu-VEGF (n = 10) within subcutaneous tumor as compared with (99m)Tc-HuS/Hu-P4G7 (n = 5) at biodistribution assay (2.68 +/- 0.75 vs. 1.8 +/- 0.21; tumor-to-subcutaneous tissue [ratio of specific activities], respectively), despite similar molecular weights. The focal (99m)Tc-HuS/Hu-VEGF uptake seen on planar images (3.44 +/- 1.16 [tumor to soft-tissue background]) corresponded directly to the locations of tumor observed by BLI. Region of interest analyses of SPECT images revealed a significant increase of (99m)Tc-HuS/Hu-VEGF (n = 5) within the lungs with BLI-detectable pulmonary tumor nodules as compared with controls (n = 4) (right: 4.47 +/- 2.07 vs. 1.79 +/- 0.56; left: 3.66 +/- 1.65 vs. 1.62 +/- 0.45, tumor lung [counts/pixel]/normal lung [counts/pixel], respectively). (99m)Tc-HuS/Hu-VEGF complex is stable for at least 1 h in vivo and can be effectively used to image mouse tumor neovasculature in lesions as small as several millimeters in soft tissue. We expect that a similar approach can be adapted for in vivo delivery of other targeting proteins of interest without affecting their bioactivity.

Clinical Application of Dual-Energy Spectral Computed Tomography in Detecting Cholesterol Gallstones From Surrounding Bile.

PubMed

Yang, Chuang-Bo; Zhang, Shuang; Jia, Yong-Jun; Duan, Hai-Feng; Ma, Guang-Ming; Zhang, Xi-Rong; Yu, Yong; He, Tai-Ping

2017-04-01

This study aimed to investigate the clinical value of spectral computed tomography (CT) in the detection of cholesterol gallstones from surrounding bile. This study was approved by the institutional review board. The unenhanced spectral CT data of 24 patients who had surgically confirmed cholesterol gallstones were analyzed. Lipid concentrations and CT numbers were measured from fat-based material decomposition image and virtual monochromatic image sets (40-140 keV), respectively. The difference in lipid concentration and CT number between cholesterol gallstones and the surrounding bile were statistically analyzed. Receiver operating characteristic analysis was applied to determine the diagnostic accuracy of using lipid concentration to differentiate cholesterol gallstones from bile. Cholesterol gallstones were bright on fat-based material decomposition images yielding a 92% detection rate (22 of 24). The lipid concentrations (552.65 ± 262.36 mg/mL), CT number at 40 keV (-31.57 ± 16.88 HU) and 140 keV (24.30 ± 5.85 HU) for the cholesterol gallstones were significantly different from those of bile (-13.94 ± 105.12 mg/mL, 12.99 ± 9.39 HU and 6.19 ± 4.97 HU, respectively). Using 182.59 mg/mL as the threshold value for lipid concentration, one could obtain sensitivity of 95.5% and specificity of 100% with accuracy of 0.994 for differentiating cholesterol gallstones from bile. Virtual monochromatic spectral CT images at 40 keV and 140 keV provide significant CT number differences between cholesterol gallstones and the surrounding bile. Spectral CT provides an excellent detection rate for cholesterol gallstones. Copyright © 2017 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.

GPRC5A is a potential oncogene in pancreatic ductal adenocarcinoma cells that is upregulated by gemcitabine with help from HuR.

PubMed

Zhou, H; Telonis, A G; Jing, Y; Xia, N L; Biederman, L; Jimbo, M; Blanco, F; Londin, E; Brody, J R; Rigoutsos, I

2016-07-14

GPRC5A is an orphan G-protein coupled receptor with an intriguing dual behavior, acting as an oncogene in some cancers and as a tumor suppressor in other cancers. In the pancreatic cancer context, very little is known about GPRC5A. By analyzing messenger RNA (mRNA) expression data from 675 human cancer cell lines and 10 609 samples from The Cancer Genome Atlas (TCGA) we found that GPRC5A's abundance in pancreatic cancer is highest (cell lines) or second highest (TCGA) among all tissues and cancer types. Further analyses of an independent set of 252 pancreatic normal and cancer samples showed GPRC5A mRNA to be more than twofold upregulated in primary tumor samples compared with normal pancreas (P-value<10(-5)), and even further upregulated in pancreatic cancer metastases to various organs (P-value=0.0021). Immunostaining of 208 cores (103 samples) of a tissue microarray showed generally low expression of GPRC5A protein in normal pancreatic ductal cells; on the other hand, in primary and metastatic samples, GPRC5A protein levels were dramatically increased in pancreatic ductal cells. In vitro studies of multiple pancreatic cancer cell lines showed that an increase in GPRC5A protein levels promoted pancreatic cancer cell growth and migration. Unexpectedly, when we treated pancreatic cancer cell lines with gemcitabine (2',2'-difluorodeoxycytidine), we observed an increase in GPRC5A protein abundance. On the other hand, when we knocked down GPRC5A we sensitized pancreatic cancer cells to gemcitabine. Through further experimentation we showed that the monotonic increase in GPRC5A protein levels that we observe for the first 18 h following gemcitabine treatment results from interactions between GPRC5A's mRNA and the RNA-binding protein HuR, which is an established key mediator of gemcitabine's efficacy in cancer cells. As we discovered, the interaction between GPRC5A and HuR is mediated by at least one HuR-binding site in GPRC5A's mRNA. Our findings indicate that GPRC5A is part of a complex molecular axis that involves gemcitabine and HuR, and, possibly, other genes. Further work is warranted before it can be established unequivocally that GPRC5A is an oncogene in the pancreatic cancer context.

Lung nodule detection in pediatric chest CT: quantitative relationship between image quality and radiologist performance.

PubMed

Li, Xiang; Samei, Ehsan; Barnhart, Huiman X; Gaca, Ana Maria; Hollingsworth, Caroline L; Maxfield, Charles M; Carrico, Caroline W T; Colsher, James G; Frush, Donald P

2011-05-01

To determine the quantitative relationship between image quality and radiologist performance in detecting small lung nodules in pediatric CT. The study included clinical chest CT images of 30 pediatric patients (0-16 years) scanned at tube currents of 55-180 mA. Calibrated noise addition software was used to simulate cases at three nominal mA settings: 70, 35, and 17.5 mA, resulting in quantum noise of 7-32 Hounsfield Unit (HU). Using a validated nodule simulation technique, lung nodules with diameters of 3-5 mm and peak contrasts of 200-500 HU were inserted into the cases, which were then randomized and rated independently by four experienced pediatric radiologists for nodule presence on a continuous scale from 0 (definitely absent) to 100 (definitely present). The receiver operating characteristic (ROC) data were analyzed to quantify the relationship between diagnostic accuracy (area under the ROC curve, AUC) and image quality (the product of nodule peak contrast and displayed diameter to noise ratio, CDNR display). AUC increased rapidly from 0.70 to 0.87 when CDNR display increased from 60 to 130 mm, followed by a slow increase to 0.94 when CDNR display further increased to 257 mm. For the average nodule diameter (4 mm) and contrast (350 HU), AUC decreased from 0.93 to 0.71 with noise increased from 7 to 28 HU. We quantified the relationship between image quality and the performance of radiologists in detecting lung nodules in pediatric CT. The relationship can guide CT protocol design to achieve the desired diagnostic performance at the lowest radiation dose.

Quantitative computed tomography and cranial burr holes: a model to evaluate the quality of cranial reconstruction in humans.

PubMed

Worm, Paulo Valdeci; Ferreira, Nelson Pires; Ferreira, Marcelo Paglioli; Kraemer, Jorge Luiz; Lenhardt, Rene; Alves, Ronnie Peterson Marcondes; Wunderlich, Ricardo Castilho; Collares, Marcus Vinicius Martins

2012-05-01

Current methods to evaluate the biologic development of bone grafts in human beings do not quantify results accurately. Cranial burr holes are standardized critical bone defects, and the differences between bone powder and bone grafts have been determined in numerous experimental studies. This study evaluated quantitative computed tomography (QCT) as a method to objectively measure cranial bone density after cranial reconstruction with autografts. In each of 8 patients, 2 of 4 surgical burr holes were reconstructed with autogenous wet bone powder collected during skull trephination, and the other 2 holes, with a circular cortical bone fragment removed from the inner table of the cranial bone flap. After 12 months, the reconstructed areas and a sample of normal bone were studied using three-dimensional QCT; bone density was measured in Hounsfield units (HU). Mean (SD) bone density was 1535.89 (141) HU for normal bone (P < 0.0001), 964 (176) HU for bone fragments, and 453 (241) HU for bone powder (P < 0.001). As expected, the density of the bone fragment graft was consistently greater than that of bone powder. Results confirm the accuracy and reproducibility of QCT, already demonstrated for bone in other locations, and suggest that it is an adequate tool to evaluate cranial reconstructions. The combination of QCT and cranial burr holes is an excellent model to accurately measure the quality of new bone in cranial reconstructions and also seems to be an appropriate choice of experimental model to clinically test any cranial bone or bone substitute reconstruction.

Comparative Recovery of Two Human Norovirus Surrogates, Feline Calicivirus and Murine Norovirus, with a Wet Vacuum System, Macrofoam-Tipped Swab, and Bottle Extraction Method from Carpets.

PubMed

Buckley, David; Fraser, Angela; Pettigrew, Charles; Anderson, Jeffery; Jiang, Xiuping

2018-05-10

Human noroviruses (HuNoV) are the leading cause of known foodborne illness in the United States, but direct detection during outbreak investigations is challenging. On the other hand, sampling both hard and soft environmental surfaces can be used to improve outbreak investigations. Currently, we lack virus recovery methods for soft surfaces, such as carpet, despite evidence suggesting that carpets contribute to HuNoV outbreaks. Our aim was to compare two recovery methods, wet vacuum and swabbing, for routine carpet sampling of HuNoV against a laboratory reference method known as bottle extraction (BE). Specifically, we compared the microbial vacuum (MVAC), macrofoam-tipped swab (MS), and BE by using HuNoV surrogates, feline calicivirus (FCV) and murine norovirus (MNV), inoculated on wool and nylon carpet carriers. The highest recovery of infectious FCV from wool was 5.51, 3.76, and 5.16 log PFU, whereas on nylon, recovery was 5.03, 3.62, and 4.75 log PFU by using BE, MS, and MVAC, respectively. On the other hand, the highest recovery of infectious MNV from wool was 6.10, 4.50, and 5.99 log PFU, while recovery on nylon was 6.07, 4.58, and 6.13 log PFU by using BE, MS, and MVAC, respectively. Significantly more PFU and genomic copies were recovered by using BE and MVAC compared with MS, while buffer type played a significant role in recovery of infectious FCV.

Modulation of prion polymerization and toxicity by rationally designed peptidomimetics.

PubMed

Srivastava, Ankit; Sharma, Sakshi; Sadanandan, Sandhya; Gupta, Sakshi; Singh, Jasdeep; Gupta, Sarika; Haridas, V; Kundu, Bishwajit

2017-01-01

Misfolding and aggregation of cellular prion protein is associated with a large array of neurological disorders commonly called the transmissible spongiform encephalopathies. Designing inhibitors against prions has remained a daunting task owing to limited information about mechanism(s) of their pathogenic self-assembly. Here, we explore the anti-prion properties of a combinatorial library of bispidine-based peptidomimetics (BPMs) that conjugate amino acids with hydrophobic and aromatic side chains. Keeping the bispidine unit unaltered, a series of structurally diverse BPMs were synthesized and tested for their prion-modulating properties. Administration of Leu- and Trp-BPMs delayed and completely inhibited the amyloidogenic conversion of human prion protein (HuPrP), respectively. We found that each BPM induced the HuPrP to form unique oligomeric nanostructures differing in their biophysical properties, cellular toxicities and response to conformation-specific antibodies. While Leu-BPMs were found to stabilize the oligomers, Trp-BPMs effected transient oligomerization, resulting in the formation of non-toxic, non-fibrillar aggregates. Yet another aromatic residue, Phe, however, accelerated the aggregation process in HuPrP. Molecular insights obtained through MD (molecular dynamics) simulations suggested that each BPM differently engages a conserved Tyr 169 residue at the α2-β2 loop of HuPrP and affects the stability of α2 and α3 helices. Our results demonstrate that this new class of molecules having chemical scaffolds conjugating hydrophobic/aromatic residues could effectively modulate prion aggregation and toxicity. © 2017 The Author(s); published by Portland Press Limited on behalf of the Biochemical Society.

Evidence that simulated microgravity may alter the vascular nonreceptor tyrosine kinase second messenger pathway

NASA Technical Reports Server (NTRS)

Kahwaji, C. I.; Sheibani, S.; Han, S.; Siu, W. O.; Kaka, A. H.; Fathy, T. M.; el-Abbadi, N. H.; Purdy, R. E.

2000-01-01

Simulated microgravity (hind limb unweighting; HU) reduces maximal contractile capacity to norepinephrine (NE) but not 5-hydroxytryptamine (5-HT) in the rat abdominal aorta of male Wistar rats. Our earlier study showed that voltage-operated calcium channels, the MAPK pathway [1], and vasoconstrictive prostaglandins contribute to the NE-induced contraction of control (C) but not HU, aorta rings. Genistein, a general tyrosine kinase inhibitor, caused a significant reduction in vascular contractility in C but not HU arteries. The present study explored the role of protein kinase C (PKC) and extracellular receptor-activated kinase 1 and 2 (ERK1/2) in the HU-induced vascular hyporesponsiveness to NE. Microgravity was simulated in Wistar rats by 20 day HU. The abdominal aorta was removed from control and HU rats, cut into 3 mm rings, and mounted in tissue baths to measure isometric contraction. Protein levels were determined using Western blot analysis. PD98059, a selective MAPKK inhibitor, caused a marked inhibition of NE-induced contraction in both C and HU arteries. Calphostin C, a PKC inhibitor, completely abolished the contractile response to NE in both C and HU tissues. Phosphorylated (activated) ERK1/2 protein mass was greater in C, compared to HU, aortas, and was reduced by genistein only in C tissues. MAPK total protein levels in the rat aorta were increased in the HU-treated, compared to C, animals. These results indicate that PKC represents an early transduction step in the contractile response to NE in the rat abdominal aorta. That inhibition of the step immediately before activation of MAPK reduced contraction in both C and HU tissues, while general tyrosine kinase inhibition with genistein blocked only the control responses, suggests that a nonreceptor tyrosine kinase may be involved in HU-induced vascular hyporesponsiveness to NE.

Nonspecific DNA Binding and Bending by HUαβ: Interfaces of the Three Binding Modes Characterized by Salt Dependent Thermodynamics

PubMed Central

Koh, Junseock; Shkel, Irina; Saecker, Ruth M.; Record, M. Thomas

2011-01-01

Previous ITC and FRET studies demonstrated that Escherichia coli HUαβ binds nonspecifically to duplex DNA in three different binding modes: a tighter-binding 34 bp mode which interacts with DNA in large (>34 bp) gaps between bound proteins, reversibly bending it 140° and thereby increasing its flexibility, and two weaker, modestly cooperative small-site-size modes (10 bp, 6 bp) useful for filling gaps between bound proteins shorter than 34 bp. Here we use ITC to determine the thermodynamics of these binding modes as a function of salt concentration, and deduce that DNA in the 34 bp mode is bent around but not wrapped on the body of HU, in contrast to specific binding of IHF. Analyses of binding isotherms (8, 15, 34 bp DNA) and initial binding heats (34, 38, 160 bp DNA) reveal that all three modes have similar log-log salt concentration derivatives of the binding constants (Ski) even though their binding site sizes differ greatly; most probable values of Ski on 34 bp or larger DNA are − 7.5 ± 0.5. From the similarity of Ski values, we conclude that binding interfaces of all three modes involve the same region of the arms and saddle of HU. All modes are entropy-driven, as expected for nonspecific binding driven by the polyelectrolyte effect. The bent-DNA 34 bp mode is most endothermic, presumably because of the cost of HU-induced DNA bending, while the 6 bp mode is modestly exothermic at all salt concentrations examined. Structural models consistent with the observed Ski values are proposed. PMID:21513716

Measurement of vascular wall attenuation: comparison of CT angiography using model-based iterative reconstruction with standard filtered back-projection algorithm CT in vitro.

PubMed

Suzuki, Shigeru; Machida, Haruhiko; Tanaka, Isao; Ueno, Eiko

2012-11-01

To compare the performance of model-based iterative reconstruction (MBIR) with that of standard filtered back projection (FBP) for measuring vascular wall attenuation. After subjecting 9 vascular models (actual attenuation value of wall, 89 HU) with wall thickness of 0.5, 1.0, or 1.5 mm that we filled with contrast material of 275, 396, or 542 HU to scanning using 64-detector computed tomography (CT), we reconstructed images using MBIR and FBP (Bone, Detail kernels) and measured wall attenuation at the center of the wall for each model. We performed attenuation measurements for each model and additional supportive measurements by a differentiation curve. We analyzed statistics using analyzes of variance with repeated measures. Using the Bone kernel, standard deviation of the measurement exceeded 30 HU in most conditions. In measurements at the wall center, the attenuation values obtained using MBIR were comparable to or significantly closer to the actual wall attenuation than those acquired using Detail kernel. Using differentiation curves, we could measure attenuation for models with walls of 1.0- or 1.5-mm thickness using MBIR but only those of 1.5-mm thickness using Detail kernel. We detected no significant differences among the attenuation values of the vascular walls of either thickness (MBIR, P=0.1606) or among the 3 densities of intravascular contrast material (MBIR, P=0.8185; Detail kernel, P=0.0802). Compared with FBP, MBIR reduces both reconstruction blur and image noise simultaneously, facilitates recognition of vascular wall boundaries, and can improve accuracy in measuring wall attenuation. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Design and development of a non-rigid phantom for the quantitative evaluation of DIR-based mapping of simulated pulmonary ventilation.

PubMed

Miyakawa, Shin; Tachibana, Hidenobu; Moriya, Shunsuke; Kurosawa, Tomoyuki; Nishio, Teiji; Sato, Masanori

2018-05-28

The validation of deformable image registration (DIR)-based pulmonary ventilation mapping is time-consuming and prone to inaccuracies and is also affected by deformation parameters. In this study, we developed a non-rigid phantom as a quality assurance (QA) tool that simulates ventilation to evaluate DIR-based images quantitatively. The phantom consists of an acrylic cylinder filled with polyurethane foam designed to simulate pulmonic alveoli. A polyurethane membrane is attached to the inferior end of the phantom to simulate the diaphragm. In addition, tracheobronchial-tree-shaped polyurethane tubes are inserted through the foam and converge outside the phantom to simulate the trachea. Solid polyurethane is also used to model arteries, which closely follow the model airways. Two three-dimensional CT scans were performed during exhalation and inhalation phases using xenon (Xe) gas as the inhaled contrast agent. The exhalation 3D-CT image is deformed to an inhalation 3D-CT image using our in-house program based on the NiftyReg open-source package. The target registration error (TRE) between the two images was calculated for 16 landmarks located in the simulated lung volume. The DIR-based ventilation image was generated using Jacobian determinant (JD) metrics. Subsequently, differences in the Hounsfield unit (HU) values between the two images were measured. The correlation coefficient between the JD and HU differences was calculated. In addition, three 4D-CT scans are performed to evaluate the reproducibility of the phantom motion and Xe gas distribution. The phantom exhibited a variety of displacements for each landmark (range: 1-20 mm). The reproducibility analysis indicated that the location differences were < 1 mm for all landmarks, and the HU variation in the Xe gas distribution was close to zero. The mean TRE in the evaluation of spatial accuracy according to the DIR software was 1.47 ± 0.71 mm (maximum: 2.6 mm). The relationship between the JD and HU differences had a large correlation (R = -0.71) for the DIR software. The phantom implemented new features, namely, deformation and simulated ventilation. To assess the accuracy of the DIR-based mapping of the simulated pulmonary ventilation, the phantom allows for simulation of Xe gas wash-in and wash-out. The phantom may be an effective QA tool, because the DIR algorithm can be quickly changed and its accuracy evaluated with a high degree of precision. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

HuR binding to cytoplasmic mRNA is perturbed by heat shock

PubMed Central

Gallouzi, Imed-Eddine; Brennan, Christopher M.; Stenberg, Myrna G.; Swanson, Maurice S.; Eversole, Ashley; Maizels, Nancy; Steitz, Joan A.

2000-01-01

AU-rich elements (AREs) located in the 3′ untranslated region target the mRNAs encoding many protooncoproteins, cytokines, and lymphokines for rapid degradation. HuR, a ubiquitously expressed member of the embryonic lethal abnormal vision (ELAV) family of RNA-binding proteins, binds ARE sequences and selectively stabilizes ARE-containing reporter mRNAs when overexpressed in transiently transfected cells. HuR appears predominantly nucleoplasmic but has been shown to shuttle between the nucleus and cytoplasm via a novel shuttling sequence HNS. We report generation of a mouse monoclonal antibody 3A2 that both immunoblots and immunoprecipitates HuR protein; it recognizes an epitope located in the first of HuR's three RNA recognition motifs. This antibody was used to probe HuR interactions with mRNA before and after heat shock, a condition that has been reported to stabilize ARE-containing mRNAs. At 37°C, approximately one-third of the cytoplasmic HuR appears polysome associated, and in vivo UV crosslinking reveals that HuR interactions with poly(A)+ RNA are predominantly cytoplasmic rather than nuclear. This comprises evidence that HuR directly interacts with mRNA in vivo. After heat shock, 12–15% of HuR accumulates in discrete foci in the cytoplasm, but surprisingly the majority of HuR crosslinks instead to nuclear poly(A)+ RNA, whose levels are dramatically increased in the stressed cells. This behavior of HuR differs from that of another ARE-binding protein, hnRNP D, which has been implicated as an effector of mRNA decay rather than mRNA stabilization and of the general pre-RNA-binding protein hnRNP A1. We interpret these differences to mean that the temporal association of HuR with ARE-containing mRNAs is different from that of these other two proteins. PMID:10737787

Downregulation of HuR Inhibits the Progression of Esophageal Cancer through Interleukin-18.

PubMed

Xu, Xiaohui; Song, Cheng; Chen, Zhihua; Yu, Chenxiao; Wang, Yi; Tang, Yiting; Luo, Judong

2018-01-01

The purpose of this study was to investigate the effect of human antigen R (HuR) downregulation and the potential target genes of HuR on the progression of esophageal squamous cell carcinoma (ESCC). In this study, a proteomics assay was used to detect the expression of proteins after HuR downregulation, and a luciferase assay was used to detect the potential presence of a HuR binding site on the 3'-untranslated region (3'-UTR) of interleukin 18 (IL-18). In addition, colony formation assay, MTT, EdU incorporation assay, Western blot, flow cytometry, immunohistochemistry, transwell invasion assay, and wound healing assay were used. In the present study, we found that the expression of both HuR protein and mRNA levels were higher in tumor tissues than in the adjacent tissues. HuR downregulation significantly suppressed cell proliferation. In addition, the metastasis of esophageal cancer cells was inhibited, while the expression of E-cadherin was increased and the expression of matrix metalloproteinase (MMP) 2, MMP9, and vimentin was decreased after HuR knockdown. Moreover, silencing of HuR disturbed the cell cycle of ESCC cells mainly by inducing G1 arrest. Furthermore, proteomics analysis showed that downregulation of HuR in TE-1 cells resulted in 100 upregulated and 122 downregulated proteins, including IL-18 as a significantly upregulated protein. The expression of IL-18 was inversely regulated by HuR. IL-18 expression was decreased in ESCC tissues, and exogenous IL-18 significantly inhibited the proliferation and metastasis of ESCC cells. The 3'-UTR of IL-18 harbored a HuR binding site, as shown by an in vitro luciferase assay. HuR plays an important role in the progression of esophageal carcinoma by targeting IL-18, which may be a potential therapeutic target for the treatment of ESCC.

Humanized Mouse Model of Skin Inflammation Is Characterized by Disturbed Keratinocyte Differentiation and Influx of IL-17A Producing T Cells

PubMed Central

de Oliveira, Vivian L.; Keijsers, Romy R. M. C.; van de Kerkhof, Peter C. M.; Seyger, Marieke M. B.; Fasse, Esther; Svensson, Lars; Latta, Markus; Norsgaard, Hanne; Labuda, Tord; Hupkens, Pieter; van Erp, Piet E. J.; Joosten, Irma; Koenen, Hans J. P. M.

2012-01-01

Humanized mouse models offer a challenging possibility to study human cell function in vivo. In the huPBL-SCID-huSkin allograft model human skin is transplanted onto immunodeficient mice and allowed to heal. Thereafter allogeneic human peripheral blood mononuclear cells are infused intra peritoneally to induce T cell mediated inflammation and microvessel destruction of the human skin. This model has great potential for in vivo study of human immune cells in (skin) inflammatory processes and for preclinical screening of systemically administered immunomodulating agents. Here we studied the inflammatory skin response of human keratinocytes and human T cells and the concomitant systemic human T cell response. As new findings in the inflamed human skin of the huPBL-SCID-huSkin model we here identified: 1. Parameters of dermal pathology that enable precise quantification of the local skin inflammatory response exemplified by acanthosis, increased expression of human β-defensin-2, Elafin, K16, Ki67 and reduced expression of K10 by microscopy and immunohistochemistry. 2. Induction of human cytokines and chemokines using quantitative real-time PCR. 3. Influx of inflammation associated IL-17A-producing human CD4+ and CD8+ T cells as well as immunoregulatory CD4+Foxp3+ cells using immunohistochemistry and -fluorescence, suggesting that active immune regulation is taking place locally in the inflamed skin. 4. Systemic responses that revealed activated and proliferating human CD4+ and CD8+ T cells that acquired homing marker expression of CD62L and CLA. Finally, we demonstrated the value of the newly identified parameters by showing significant changes upon systemic treatment with the T cell inhibitory agents cyclosporine-A and rapamycin. In summary, here we equipped the huPBL-SCID-huSkin humanized mouse model with relevant tools not only to quantify the inflammatory dermal response, but also to monitor the peripheral immune status. This combined approach will gain our understanding of the dermal immunopathology in humans and benefit the development of novel therapeutics for controlling inflammatory skin diseases. PMID:23094018

Repeated Gestational Exposure of Mice to Chlorpyrifos Oxon Is Associated with Paraoxonase 1 (PON1) Modulated Effects in Maternal and Fetal Tissues

PubMed Central

Co, Aila L.; Hay, Ariel M.; MacDonald, James W.; Bammler, Theo K.; Farin, Federico M.; Costa, Lucio G.; Furlong, Clement E.

2014-01-01

Chlorpyrifos oxon (CPO), the toxic metabolite of the organophosphorus (OP) insecticide chlorpyrifos, causes developmental neurotoxicity in humans and rodents. CPO is hydrolyzed by paraoxonase-1 (PON1), with protection determined by PON1 levels and the human Q192R polymorphism. To examine how the Q192R polymorphism influences fetal toxicity associated with gestational CPO exposure, we measured enzyme inhibition and fetal-brain gene expression in wild-type (PON1+/+), PON1-knockout (PON1−/−), and tgHuPON1R192 and tgHuPON1Q192 transgenic mice. Pregnant mice exposed dermally to 0, 0.50, 0.75, or 0.85 mg/kg/d CPO from gestational day (GD) 6 through 17 were sacrificed on GD18. Biomarkers of CPO exposure inhibited in maternal tissues included brain acetylcholinesterase (AChE), red blood cell acylpeptide hydrolase (APH), and plasma butyrylcholinesterase (BChE) and carboxylesterase (CES). Fetal plasma BChE was inhibited in PON1−/− and tgHuPON1Q192, but not PON1+/+ or tgHuPON1R192 mice. Fetal brain AChE and plasma CES were inhibited in PON1−/− mice, but not in other genotypes. Weighted gene co-expression network analysis identified five gene modules based on clustering of the correlations among their fetal-brain expression values, allowing for correlation of module membership with the phenotypic data on enzyme inhibition. One module that correlated highly with maternal brain AChE activity had a large representation of homeobox genes. Gene set enrichment analysis revealed multiple gene sets affected by gestational CPO exposure in tgHuPON1Q192 but not tgHuPON1R192 mice, including gene sets involved in protein export, lipid metabolism, and neurotransmission. These data indicate that maternal PON1 status modulates the effects of repeated gestational CPO exposure on fetal-brain gene expression and on inhibition of both maternal and fetal biomarker enzymes. PMID:25070982

Neuronal uptake of anti-Hu antibody, but not anti-Ri antibody, leads to cell death in brain slice cultures.

PubMed

Greenlee, John E; Clawson, Susan A; Hill, Kenneth E; Wood, Blair; Clardy, Stacey L; Tsunoda, Ikuo; Jaskowski, Troy D; Carlson, Noel G

2014-09-17

Anti-Hu and anti-Ri antibodies are paraneoplastic immunoglobulin (Ig)G autoantibodies which recognize cytoplasmic and nuclear antigens present in all neurons. Although both antibodies produce similar immunohistological labeling, they recognize different neuronal proteins. Both antibodies are associated with syndromes of central nervous system dysfunction. However, the neurological deficits associated with anti-Hu antibody are associated with neuronal death and are usually irreversible, whereas neurological deficits in patients with anti-Ri antibody may diminish following tumor removal or immunosuppression. To study the effect of anti-Hu and anti-Ri antibodies on neurons, we incubated rat hippocampal and cerebellar slice cultures with anti-Hu or anti-Ri sera from multiple patients. Cultures were evaluated in real time for neuronal antibody uptake and during prolonged incubation for neuronal death. To test the specificity of anti-Hu antibody cytotoxic effect, anti-Hu serum IgG was incubated with rat brain slice cultures prior to and after adsorption with its target Hu antigen, HuD. We demonstrated that: 1) both anti-Hu and anti-Ri antibodies were rapidly taken up by neurons throughout both cerebellum and hippocampus; 2) antibody uptake occurred in living neurons and was not an artifact of antibody diffusion into dead cells; 3) intracellular binding of anti-Hu antibody produced neuronal cell death, whereas uptake of anti-Ri antibody did not affect cell viability during the period of study; and 4) adsorption of anti-Hu antisera against HuD greatly reduced intraneuronal IgG accumulation and abolished cytotoxicity, confirming specificity of antibody-mediated neuronal death. Both anti-Hu and anti-Ri antibodies were readily taken up by viable neurons in slice cultures, but the two antibodies differed markedly in terms of their effects on neuronal viability. The ability of anti-Hu antibodies to cause neuronal death could account for the irreversible nature of paraneoplastic neurological deficits in patients with this antibody response. Our results raise questions as to whether anti-Ri antibody might initially induce reversible neuronal dysfunction, rather than causing cell death. The ability of IgG antibodies to access and react with intracellular neuronal proteins could have implications for other autoimmune diseases involving the central nervous system.

The ELAV RNA-stability factor HuR binds the 5′-untranslated region of the human IGF-IR transcript and differentially represses cap-dependent and IRES-mediated translation

PubMed Central

Meng, Zheng; King, Peter H.; Nabors, L. Burt; Jackson, Nateka L.; Chen, Ching-Yi; Emanuel, Peter D.; Blume, Scott W.

2005-01-01

The type I insulin-like growth factor receptor (IGF-IR) is an integral component in the control of cell proliferation, differentiation and apoptosis. The IGF-IR mRNA contains an extraordinarily long (1038 nt) 5′-untranslated region (5′-UTR), and we have characterized a diverse series of proteins interacting with this RNA sequence which may provide for intricate regulation of IGF-IR gene expression at the translational level. Here, we report the purification and identification of one of these IGF-IR 5′-UTR-binding proteins as HuR, using a novel RNA crosslinking/RNase elution strategy. Because HuR has been predominantly characterized as a 3′-UTR-binding protein, enhancing mRNA stability and generally increasing gene expression, we sought to determine whether HuR might serve a different function in the context of its binding the IGF-IR 5′-UTR. We found that HuR consistently repressed translation initiation through the IGF-IR 5′-UTR. The inhibition of translation by HuR was concentration dependent, and could be reversed in trans by addition of a fragment of the IGF-IR 5′-UTR containing the HuR binding sites as a specific competitor, or abrogated by deletion of the third RNA recognition motif of HuR. We determined that HuR repressed translation initiation through the IGF-IR 5′-UTR in cells as well, and that siRNA knockdown of HuR markedly increased IGF-IR protein levels. Interestingly, we also found that HuR potently inhibited IGF-IR translation mediated through internal ribosome entry. Kinetic assays were performed to investigate the mechanism of translation repression by HuR and the dynamic interplay between HuR and the translation apparatus. We found that HuR, occupying a cap-distal position, significantly delayed translation initiation mediated by cap-dependent scanning, but was eventually displaced from its binding site, directly or indirectly, as a consequence of ribosomal scanning. However, HuR perpetually blocked the activity of the IGF-IR IRES, apparently arresting the IRES-associated translation pre-initiation complex in an inactive state. This function of HuR as a 5′-UTR-binding protein and dual-purpose translation repressor may be critical for the precise regulation of IGF-IR expression essential to normal cellular homeostasis. PMID:15914670

Recovery Optimization and Survival of the Human Norovirus Surrogates Feline Calicivirus and Murine Norovirus on Carpet

PubMed Central

Buckley, David; Fraser, Angela; Huang, Guohui

2017-01-01

ABSTRACT Carpets have been implicated in prolonged and reoccurring outbreaks of human noroviruses (HuNoV), the leading cause of acute gastroenteritis worldwide. Viral recovery from environmental surfaces, such as carpet, remains undeveloped. Our aim was to determine survival of HuNoV surrogates on an understudied environmental surface, carpet. First, we measured the zeta potential and absorption capacity of wool and nylon carpet fibers, we then developed a minispin column elution (MSC) method, and lastly we characterized the survival of HuNoV surrogates, feline calicivirus (FCV) and murine norovirus (MNV), over 60 days under 30 and 70% relative humidity (RH) on two types of carpet and one glass surface. Carpet surface charge was negative between relevant pH values (i.e., pH 7 to 9). In addition, wool could absorb approximately two times more liquid than nylon. The percent recovery efficiency obtained by the MSC method ranged from 4.34 to 20.89% and from 30.71 to 54.14% for FCV and MNV on carpet fibers, respectively, after desiccation. Overall, elution buffer type did not significantly affect recovery. Infectious FCV or MNV survived between <1 and 15 or between 3 and 15 days, respectively. However, MNV survived longer under some conditions and at significantly (P < 0.05) higher titers compared to FCV. Albeit, surrogates followed similar survival trends, i.e., both survived longest on wool then nylon and glass, while 30% RH provided a more hospitable environment compared to 70% RH. Reverse transcription-quantitative PCR signals for both surrogates were detectable for the entire study, but FCV genomic copies experienced significantly higher reductions (<3.80 log10 copies) on all surfaces compared to MNV (<1.10 log10 copies). IMPORTANCE Human noroviruses (HuNoV) are the leading cause of acute gastroenteritis worldwide. Classical symptoms of illness include vomiting and diarrhea which could lead to severe dehydration and death. HuNoV are transmitted by the fecal-oral or vomitus-oral route via person-to-person contact, food, water, and/or environmental surfaces. Published laboratory-controlled studies have documented the environmental stability of HuNoV on hard surfaces, but there is limited laboratory-based evidence available about survival on soft surfaces, e.g., carpet and upholstered furniture. Several epidemiological reports have suggested soft surfaces may be HuNoV fomites illustrating the importance of conducting a survival study. The three objectives of our research were to demonstrate techniques to characterize soft surfaces, develop a viral elution method for carpet, and characterize the survival of HuNoV surrogates on carpet. These results can be used to improve microbial risk assessments, the development of much-needed soft surface disinfectant, and standardizing protocols for future soft surface studies. PMID:28864657

CB2 cannabinoid receptor agonist enantiomers HU-433 and HU-308: An inverse relationship between binding affinity and biological potency.

PubMed

Smoum, Reem; Baraghithy, Saja; Chourasia, Mukesh; Breuer, Aviva; Mussai, Naama; Attar-Namdar, Malka; Kogan, Natalya M; Raphael, Bitya; Bolognini, Daniele; Cascio, Maria G; Marini, Pietro; Pertwee, Roger G; Shurki, Avital; Mechoulam, Raphael; Bab, Itai

2015-07-14

Activation of the CB2 receptor is apparently an endogenous protective mechanism. Thus, it restrains inflammation and protects the skeleton against age-related bone loss. However, the endogenous cannabinoids, as well as Δ(9)-tetrahydrocannabinol, the main plant psychoactive constituent, activate both cannabinoid receptors, CB1 and CB2. HU-308 was among the first synthetic, selective CB2 agonists. HU-308 is antiosteoporotic and antiinflammatory. Here we show that the HU-308 enantiomer, designated HU-433, is 3-4 orders of magnitude more potent in osteoblast proliferation and osteoclast differentiation culture systems, as well as in mouse models, for the rescue of ovariectomy-induced bone loss and ear inflammation. HU-433 retains the HU-308 specificity for CB2, as shown by its failure to bind to the CB1 cannabinoid receptor, and has no activity in CB2-deficient cells and animals. Surprisingly, the CB2 binding affinity of HU-433 in terms of [(3)H]CP55,940 displacement and its effect on [(35)S]GTPγS accumulation is substantially lower compared with HU-308. A molecular-modeling analysis suggests that HU-433 and -308 have two different binding conformations within CB2, with one of them possibly responsible for the affinity difference, involving [(35)S]GTPγS and cAMP synthesis. Hence, different ligands may have different orientations relative to the same binding site. This situation questions the usefulness of universal radioligands for comparative binding studies. Moreover, orientation-targeted ligands have promising potential for the pharmacological activation of distinct processes.

CB2 cannabinoid receptor agonist enantiomers HU-433 and HU-308: An inverse relationship between binding affinity and biological potency

PubMed Central

Smoum, Reem; Baraghithy, Saja; Chourasia, Mukesh; Breuer, Aviva; Mussai, Naama; Attar-Namdar, Malka; Kogan, Natalya M.; Raphael, Bitya; Bolognini, Daniele; Cascio, Maria G.; Marini, Pietro; Pertwee, Roger G.; Shurki, Avital; Mechoulam, Raphael; Bab, Itai

2015-01-01

Activation of the CB2 receptor is apparently an endogenous protective mechanism. Thus, it restrains inflammation and protects the skeleton against age-related bone loss. However, the endogenous cannabinoids, as well as Δ9-tetrahydrocannabinol, the main plant psychoactive constituent, activate both cannabinoid receptors, CB1 and CB2. HU-308 was among the first synthetic, selective CB2 agonists. HU-308 is antiosteoporotic and antiinflammatory. Here we show that the HU-308 enantiomer, designated HU-433, is 3–4 orders of magnitude more potent in osteoblast proliferation and osteoclast differentiation culture systems, as well as in mouse models, for the rescue of ovariectomy-induced bone loss and ear inflammation. HU-433 retains the HU-308 specificity for CB2, as shown by its failure to bind to the CB1 cannabinoid receptor, and has no activity in CB2-deficient cells and animals. Surprisingly, the CB2 binding affinity of HU-433 in terms of [3H]CP55,940 displacement and its effect on [35S]GTPγS accumulation is substantially lower compared with HU-308. A molecular-modeling analysis suggests that HU-433 and -308 have two different binding conformations within CB2, with one of them possibly responsible for the affinity difference, involving [35S]GTPγS and cAMP synthesis. Hence, different ligands may have different orientations relative to the same binding site. This situation questions the usefulness of universal radioligands for comparative binding studies. Moreover, orientation-targeted ligands have promising potential for the pharmacological activation of distinct processes. PMID:26124120

Recombinant human erythropoietin improves gut barrier function in a hemorrhagic shock and resuscitation rat model.

PubMed

Kao, N Raymond L C; Xenocostas, Anargyros; Driman, David K; Rui, Tao; Huang, Weixiong; Jiao, Xiujun; Martin, Claudio M

2011-11-01

Gut injury and bacterial translocation develop and persist after limited periods of hemorrhagic shock. Erythropoietin (EPO) can exert hemodynamic, anti-inflammatory, and tissue protective effects. We tested the hypothesis that EPO given at the time of resuscitation with saline will reduce functional ileal injury 24 hours after shock. Sprague-Dawley rats (n = 6 per group) were randomized to sham surgery or hemorrhagic shock maintained at mean arterial pressure 40 mm Hg for 60 minutes and then treated with either saline resuscitation (three times the volume of shed blood) or saline + recombinant human EPO (rHuEPO) resuscitation. Intravenous rHuEPO (1,000 U/kg) was given at the start of saline resuscitation, and at 24 hours ileal function was evaluated using quantitative cultures of mesenteric lymph nodes to assess for bacterial translocation (colony-forming units per gram of tissue [CFU/g]), determination of portal vein plasma endotoxin levels and histopathological evaluation using semi-thin plastic sections of the distal ileum. In a second series of animals, fluorescein isothiocyanate-dextran 4000 (FD-4) was used to assess mucosal permeability of the distal ileum to macromolecules. At 24 hours, the saline group had morphologic evidence of intestinal injury when compared with the sham group, and the degree of mucosal injury was less in the saline + rHuEPO when compared with the saline group, which demonstrated significantly reduced bacterial translocation to the mesenteric lymph nodes (383 CFU/g ± 111 CFU/g vs. 1130 CFU/g ± 297 CFU/g; p < 0.05) and decreased terminal ileum permeability to FD-4 (3.08 μg/mL ± 0.31 μg/mL vs. 5.14 μg/mL ± 0.88 μg/mL; p < 0.05). No significant difference was found in the portal vein endotoxin levels between the two groups. Histopathological evaluation demonstrated a trend for decreased enterocyte disarray or disruption and vacuolization in the saline + rHuEPO versus saline group. Using rHuEPO at time of saline resuscitation resulted in decreased bacterial translocation and permeability to macromolecules 24 hours after shock. These observations suggest that rHuEPO can mediate a protective effect on intestinal mucosal barrier function during ischemic injury.

Erythropoietin, Iron Depletion and Relative Thrombocytosis: A Possible Explanation for Hemoglobin-Survival Paradox in Chronic Kidney Disease

PubMed Central

Streja, Elani; Kovesdy, Csaba P; Greenland, Sander; Kopple, Joel D.; McAllister, Charles J; Nissenson, Allen R; Kalantar-Zadeh, Kamyar

2017-01-01

Background High doses of human recombinant erythropoietin (rHuEPO) to achieve hemoglobin levels above 13 g/dL in chronic kidney disease appear associated with elevated mortality. Study Design We conducted logistic regression and survival analyses in a retrospective cohort of maintenance hemodialysis (MHD) patients to examine the hypothesis that the induced iron depletion with resultant relative thrombocytosis may be a possible contributor to the link between the high rHuEPO dose associated hemoglobin ≥13 g/dL and mortality. Setting & Participants The national database of a large dialysis organization (DaVita) with 40,787 MHD patients during July to December 2001 and their survival up to July 2004 were examined. Predictors Hemoglobin level, platelet count and administered rHuEPO dose during each calendar quarter. Outcomes & other Measurements Case-mix adjusted 3-year all-cause mortality; and measures of iron stores including serum ferritin and iron saturation ratio (ISAT). Results Higher platelet count was associated with lower iron stores and higher prescribed rHuEPO dose. Compared to hemoglobin of 12-13 g/dL, hemoglobin ≥13 g/dL was associated with increased mortality in the presence of relative thrombocytosis, i.e., platelet count ≥300,000/μl, (case-mix adjusted death-rate ratio [RR]: 1.21, 95% confidence limits [CL]: 1.02–1.44, P=0.03) as opposed to the absence of relative thrombocytosis (RR: 1.04, 95% CL: 0.98–1.08, P=0.13). Prescribed rHuEPO dose >20,000 units/week was associated with higher likelihood of iron depletion (ISAT<20%) and relative thrombocytosis (case-mix adjusted odds ratio: 2.53 [CL: 2.37–2.69] and 1.36 [CL: 1.30–1.42], respectively, p<0.001) and increased mortality over 3 years (death-rate ratio of 1.59, CL: 1.54, 1.65, p<0.001). Limitations Our results may incorporate uncontrolled confounding. Achieved hemoglobin may have different mortality-predictability than targeted hemoglobin. Conclusions Iron depletion and associated relative thrombocytosis might contribute to increased mortality when administering high rHuEPO doses to achieve hemoglobin ≥13 g/dL in MHD patients. Randomized trials are needed to test these observational associations. PMID:18760517

Early changes of parotid density and volume predict modifications at the end of therapy and intensity of acute xerostomia.

PubMed

Belli, Maria Luisa; Scalco, Elisa; Sanguineti, Giuseppe; Fiorino, Claudio; Broggi, Sara; Dinapoli, Nicola; Ricchetti, Francesco; Valentini, Vincenzo; Rizzo, Giovanna; Cattaneo, Giovanni Mauro

2014-10-01

To quantitatively assess the predictive power of early variations of parotid gland volume and density on final changes at the end of therapy and, possibly, on acute xerostomia during IMRT for head-neck cancer. Data of 92 parotids (46 patients) were available. Kinetics of the changes during treatment were described by the daily rate of density (rΔρ) and volume (rΔvol) variation based on weekly diagnostic kVCT images. Correlation between early and final changes was investigated as well as the correlation with prospective toxicity data (CTCAEv3.0) collected weekly during treatment for 24/46 patients. A higher rΔρ was observed during the first compared to last week of treatment (-0,50 vs -0,05HU, p-value = 0.0001). Based on early variations, a good estimation of the final changes may be obtained (Δρ: AUC = 0.82, p = 0.0001; Δvol: AUC = 0.77, p = 0.0001). Both early rΔρ and rΔvol predict a higher "mean" acute xerostomia score (≥ median value, 1.57; p-value = 0.01). Median early density rate changes for patients with mean xerostomia score ≥ / < 1.57 were -0.98 vs -0.22 HU/day respectively (p = 0.05). Early density and volume variations accurately predict final changes of parotid glands. A higher longitudinally assessed score of acute xerostomia is well predicted by higher rΔρ and rΔvol in the first two weeks of treatment: best cut-off values were -0.50 HU/day and -380 mm(3)/day for rΔρ and rΔvol respectively. Further studies are necessary to definitively assess the potential of early density/volume changes in identifying more sensitive patients at higher risk of experiencing xerostomia.

Experimental verification of ion stopping power prediction from dual energy CT data in tissue surrogates

NASA Astrophysics Data System (ADS)

Farace, Paolo

2014-11-01

A two-steps procedure is presented to convert dual-energy CT data to stopping power ratio (SPR), relative to water. In the first step the relative electron density (RED) is calculated from dual-energy CT-numbers by means of a bi-linear relationship: RED = a HUscH + b HUscL + c, where HUscH and HUscL are scaled units (HUsc = HU + 1000) acquired at high and low energy respectively, and the three parameters a, b and c has to be determined for each CT scanner. In the second step the RED values were converted into SPR by means of published poly-line functions, which are invariant as they do not depend on a specific CT scanner. The comparison with other methods provides encouraging results, with residual SPR error on human tissue within 1%. The distinctive features of the proposed method are its simplicity and the generality of the conversion functions.

Experimental verification of ion stopping power prediction from dual energy CT data in tissue surrogates.

PubMed

Farace, Paolo

2014-11-21

A two-steps procedure is presented to convert dual-energy CT data to stopping power ratio (SPR), relative to water. In the first step the relative electron density (RED) is calculated from dual-energy CT-numbers by means of a bi-linear relationship: RED=a HUscH+b HUscL+c, where HUscH and HUscL are scaled units (HUsc=HU+1000) acquired at high and low energy respectively, and the three parameters a, b and c has to be determined for each CT scanner. In the second step the RED values were converted into SPR by means of published poly-line functions, which are invariant as they do not depend on a specific CT scanner. The comparison with other methods provides encouraging results, with residual SPR error on human tissue within 1%. The distinctive features of the proposed method are its simplicity and the generality of the conversion functions.

The Elav-like protein HuR exerts translational control of viral internal ribosome entry sites

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rivas-Aravena, Andrea; Ramdohr, Pablo; Vallejos, Maricarmen

2009-09-30

The human embryonic-lethal abnormal vision (ELAV)-like protein, HuR, has been recently found to be involved in the regulation of protein synthesis. In this study we show that HuR participates in the translational control of the HIV-1 and HCV IRES elements. HuR functions as a repressor of HIV-1 IRES activity and acts as an activator of the HCV IRES. The effect of HuR was evaluated in three independent experimental systems, rabbit reticulocyte lysate, HeLa cells, and Xenopus laevis oocytes, using both overexpression and knockdown approaches. Furthermore, results suggest that HuR mediated regulation of HIV-1 and HCV IRESes does not require directmore » binding of the protein to the RNA nor does it need the nuclear translocation of the IRES-containing RNAs. Finally, we show that HuR has a negative impact on post-integration steps of the HIV-1 replication cycle. Thus, our observations yield novel insights into the role of HuR in the post-transcriptional regulation of HCV and HIV-1 gene expression.« less

VX hydrolysis by human serum paraoxonase 1: a comparison of experimental and computational results.

PubMed

Peterson, Matthew W; Fairchild, Steven Z; Otto, Tamara C; Mohtashemi, Mojdeh; Cerasoli, Douglas M; Chang, Wenling E

2011-01-01

Human Serum paraoxonase 1 (HuPON1) is an enzyme that has been shown to hydrolyze a variety of chemicals including the nerve agent VX. While wildtype HuPON1 does not exhibit sufficient activity against VX to be used as an in vivo countermeasure, it has been suggested that increasing HuPON1's organophosphorous hydrolase activity by one or two orders of magnitude would make the enzyme suitable for this purpose. The binding interaction between HuPON1 and VX has recently been modeled, but the mechanism for VX hydrolysis is still unknown. In this study, we created a transition state model for VX hydrolysis (VX(ts)) in water using quantum mechanical/molecular mechanical simulations, and docked the transition state model to 22 experimentally characterized HuPON1 variants using AutoDock Vina. The HuPON1-VX(ts) complexes were grouped by reaction mechanism using a novel clustering procedure. The average Vina interaction energies for different clusters were compared to the experimentally determined activities of HuPON1 variants to determine which computational procedures best predict how well HuPON1 variants will hydrolyze VX. The analysis showed that only conformations which have the attacking hydroxyl group of VX(ts) coordinated by the sidechain oxygen of D269 have a significant correlation with experimental results. The results from this study can be used for further characterization of how HuPON1 hydrolyzes VX and design of HuPON1 variants with increased activity against VX.

VX Hydrolysis by Human Serum Paraoxonase 1: A Comparison of Experimental and Computational Results

PubMed Central

Peterson, Matthew W.; Fairchild, Steven Z.; Otto, Tamara C.; Mohtashemi, Mojdeh; Cerasoli, Douglas M.; Chang, Wenling E.

2011-01-01

Human Serum paraoxonase 1 (HuPON1) is an enzyme that has been shown to hydrolyze a variety of chemicals including the nerve agent VX. While wildtype HuPON1 does not exhibit sufficient activity against VX to be used as an in vivo countermeasure, it has been suggested that increasing HuPON1's organophosphorous hydrolase activity by one or two orders of magnitude would make the enzyme suitable for this purpose. The binding interaction between HuPON1 and VX has recently been modeled, but the mechanism for VX hydrolysis is still unknown. In this study, we created a transition state model for VX hydrolysis (VXts) in water using quantum mechanical/molecular mechanical simulations, and docked the transition state model to 22 experimentally characterized HuPON1 variants using AutoDock Vina. The HuPON1-VXts complexes were grouped by reaction mechanism using a novel clustering procedure. The average Vina interaction energies for different clusters were compared to the experimentally determined activities of HuPON1 variants to determine which computational procedures best predict how well HuPON1 variants will hydrolyze VX. The analysis showed that only conformations which have the attacking hydroxyl group of VXts coordinated by the sidechain oxygen of D269 have a significant correlation with experimental results. The results from this study can be used for further characterization of how HuPON1 hydrolyzes VX and design of HuPON1 variants with increased activity against VX. PMID:21655255

Intestinal microbiota contributes to colonic epithelial changes in simulated microgravity mouse model.

PubMed

Shi, Junxiu; Wang, Yifan; He, Jian; Li, Pingping; Jin, Rong; Wang, Ke; Xu, Xi; Hao, Jie; Zhang, Yan; Liu, Hongju; Chen, Xiaoping; Wu, Hounan; Ge, Qing

2017-08-01

Exposure to microgravity leads to alterations in multiple systems, but microgravity-related changes in the gastrointestinal tract and its clinical significance have not been well studied. We used the hindlimb unloading (HU) mouse model to simulate a microgravity condition and investigated the changes in intestinal microbiota and colonic epithelial cells. Compared with ground-based controls (Ctrls), HU affected fecal microbiota composition with a profile that was characterized by the expansion of Firmicutes and decrease of Bacteroidetes. The colon epithelium of HU mice showed decreased goblet cell numbers, reduced epithelial cell turnover, and decreased expression of genes that are involved in defense and inflammatory responses. As a result, increased susceptibility to dextran sulfate sodium-induced epithelial injury was observed in HU mice. Cohousing of Ctrl mice with HU mice resulted in HU-like epithelial changes in Ctrl mice. Transplantation of feces from Ctrl to HU mice alleviated these epithelial changes in HU mice. Results indicate that HU changes intestinal microbiota, which leads to altered colonic epithelial cell homeostasis, impaired barrier function, and increased susceptibility to colitis. We further demonstrate that alteration in gastrointestinal motility may contribute to HU-associated dysbiosis. These animal results emphasize the necessity of evaluating astronauts' intestinal homeostasis during distant space travel.-Shi, J., Wang, Y., He, J., Li, P., Jin, R., Wang, K., Xu, X., Hao, J., Zhang, Y., Liu, H., Chen, X., Wu, H., Ge, Q. Intestinal microbiota contributes to colonic epithelial changes in simulated microgravity mouse model. © FASEB.

Characterization of the hypothermic effect of the synthetic cannabinoid HU-210 in the rat. Relation to the adrenergic system and endogenous pyrogens.

PubMed

Ovadia, H; Wohlman, A; Mechoulam, R; Weidenfeld, J

1995-02-01

In the present study we have characterized the hypothermic effect of the psychoactive cannabinoid HU-210, by investigating its interaction with the endogenous pyrogens, IL-1 and PGE2. We also studied the involvement of the adrenergic system in mediation of this hypothermic effect. Injection of HU-210 directly into the preoptic area caused a dose dependent reduction of rectal temperature from 37 to 32.1 degrees C. Injection of the non-psychoactive analog, HU-211 which does not bind to brain cannabinoid receptor, did not affect body temperature. Injection of the adrenergic agonists, CGP-12177 and clonidine (beta, and alpha adrenergic agonists, respectively) abrogated the hypothermia induced by HU-210. Injection of the adrenergic antagonists, prazosin (alpha 1) and propranolol (beta) enhanced the hypothermic effect of HU-210. Intracerebral administration of IL-1 or PGE2 to rats pretreated with HU-210 caused a transient inhibition of the hypothermia. The ex vivo rate of basal or bacterial endotoxin-induced synthesis of PGE2 by different brain regions, including the preoptic area was not affected by HU-210 administration. These results suggest that the synthetic cannabinoid HU-210 acts in the preoptic area, probably via the brain cannabinoid receptor to induce hypothermia. The hypothermic effect can be antagonized by adrenergic agonists and enhanced by adrenergic antagonists. HU-210 does not interfere with the pyrogenic effect of IL-1 or PGE2.

Curcumin Suppresses In Vitro Proliferation and Invasion of Human Prostate Cancer Stem Cells by Modulating DLK1-DIO3 Imprinted Gene Cluster MicroRNAs.

PubMed

Zhang, Hu; Zheng, Jiajia; Shen, Hongliang; Huang, Yongyi; Liu, Te; Xi, Hao; Chen, Chuan

2018-01-01

Curcumin can suppress human prostate cancer (HuPCa) cell proliferation and invasion. However, it is not known whether curcumin can inhibit HuPCa stem cell (HuPCaSC) proliferation and invasion. We used methyl thiazolyl tetrazolium and Transwell assays to examine the proliferation and invasion of the HuPCaSC lines DU145 and 22Rv1 following curcumin or dimethyl sulfoxide (control) treatment. The microRNA (miRNA) expression levels in the DLK1-DIO3 imprinted genomic region in the cells and in tumor tissues from patients with PCa were examined using microarray and quantitative PCR. The median inhibitory concentration of curcumin for HuPCa cells significantly inhibited HuPCaSC proliferation and invasion in vitro. The miR-770-5p and miR-1247 expression levels in the DLK1-DIO3 imprinted gene cluster were significantly different between the curcumin-treated and control HuPCaSCs. Overexpression of these positive miRNAs significantly increased the inhibition rates of miR-770-5p- and miR-1247-transfected HuPCaSCs compared to the control miR-Mut-transfected HuPCaSCs. Lastly, low-tumor grade PCa tissues had higher miR-770-5p and miR-1247 expression levels than high-grade tumor tissues. Curcumin can suppress HuPCaSC proliferation and invasion in vitro by modulating specific miRNAs in the DLK1-DIO3 imprinted gene cluster.

Site- and compartment-specific changes in bone with hindlimb unloading in mature adult rats

NASA Technical Reports Server (NTRS)

Bloomfield, S. A.; Allen, M. R.; Hogan, H. A.; Delp, M. D.

2002-01-01

The purpose of this study was to examine site- and compartment-specific changes in bone induced by hindlimb unloading (HU) in the mature adult male rat (6 months old). Tibiae, femora, and humeri were removed after 14, 21, and 28 days of HU for determination of bone mineral density (BMD) and geometry by peripheral quantitative computed tomography (pQCT), mechanical properties, and bone formation rate (BFR), and compared with baseline (0 day) and aging (28 day) controls. HU resulted in 20%-21% declines in cancellous BMD at the proximal tibia and femoral neck after 28 day HU vs. 0 day controls (CON). Cortical shell BMD at these sites was greater (by 4%-6%) in both 28 day HU and 28 day CON vs. 0 day CON animals, and nearly identical to that gain seen in the weight-bearing humerus. Mechanical properties at the proximal tibia exhibited a nonsignificant decline after HU vs. those of 0 day CON rats. At the femoral neck, a 10% decrement was noted in ultimate load in 28 day HU rats vs. 28 day CON animals. Middiaphyseal tibial bone increased slightly in density and area during HU; no differences in structural and material properties between 28 day HU and 28 day CON rats were noted. BFR at the tibial midshaft was significantly lower (by 90%) after 21 day HU vs. 0 day CON; this decline was maintained throughout 28 day HU. These results suggest there are compartment-specific differences in the mature adult skeletal response to hindlimb unloading, and that the major impact over 28 days of unloading is on cancellous bone sites. Given the sharp decline in BFR for midshaft cortical bone, it appears likely that deficits in BMD, area, or mechanical properties would develop with longer duration unloading.

Chronic treatment with recombinant human erythropoietin exerts renoprotective effects beyond hematopoiesis in streptozotocin-induced diabetic rat.

PubMed

Toba, Hiroe; Sawai, Naoki; Morishita, Masayuki; Murata, Shoko; Yoshida, Mamiko; Nakashima, Kohei; Morita, Yosuke; Kobara, Miyuki; Nakata, Tetsuo

2009-06-10

Recombinant human erythropoietin (rHuEPO), which has been used clinically for the management of renal anemia, is reported to exert pleiotropic beneficial properties against acute ischemic/reperfusion injury in various tissues. To investigate the hypothesis that chronic treatment with rHuEPO might ameliorate diabetic nephropathy beyond hematopoiesis, rHuEPO (150 U/kg, subcutaneously) was administered three times per week to the streptozotocin-induced diabetic rats for 4 weeks. Streptozotocin (65 mg/kg, intravenously) significantly increased urinary protein excretion and collagen deposition in glomerular and tubulointerstitial areas in the kidney, which were attenuated by rHuEPO. rHuEPO normalized the levels of creatinine clearance, serum creatinine, and blood urea nitrogen of diabetic rats. RT-PCR analysis revealed that the expressions of mRNA for transforming growth factor-beta, osteopontin and adhesion molecules were enhanced in the diabetic rat kidney and that the overexpression of these molecules was suppressed by rHuEPO. rHuEPO exerted antioxidant properties by inhibiting renal activation and overexpression of NADPH oxidase. We found the activation of the Akt signaling pathway by the increased expression of phosphorylated Akt and GSK-3beta and a reduction of TUNEL-positive apoptotic cell death in renal tissue from rHuEPO-treated diabetic group. We also demonstrated that rHuEPO restored the endothelial nitric oxide synthase (eNOS) content in the diabetic rat kidney. On the other hand, treatment with rHuEPO did not affect blood glucose level, blood pressure, or hematocrit in diabetic rats. These results suggest that chronic treatment with rHuEPO attenuated renal injury beyond hematopoiesis and regulated apoptosis and eNOS expression, which might be due to the activation of Akt pathway.

Changes in urine albumin to creatinine ratio with the initiation of hydroxyurea therapy among children and adolescents with sickle cell disease.

PubMed

Tehseen, Sarah; Joiner, Clinton H; Lane, Peter A; Yee, Marianne E

2017-12-01

Renal damage is a progressive complication of sickle cell disease (SCD) that begins in childhood and may progress to renal failure and early mortality in 12% of adults with hemoglobin SS (HbSS) SCD. Early sickle nephropathy is characterized by hyperfiltration and microalbuminuria; therefore, urine albumin to creatinine ratio (ACR) is an effective screening tool for its detection. This study investigated the effect of hydroxyurea (HU) therapy on urine ACR levels among children with SCD. A retrospective review was conducted to identify all patients with HbSS or HbSβ 0 thalassemia of age 7-18 years who began HU therapy in 2011-2013; a control group of patients not on HU were matched by age and baseline hemoglobin. All urine ACR measurements ≤24 months prior to and ≥24 months after HU initiation were recorded. There were 63 eligible patients on HU and 13 (25%) with albuminuria prior to HU initiation. Among those with baseline albuminuria, the median ACR was 96 mg/g prior to HU, 39 mg/g at 1 year (P = 0.02), and 25 mg/g at 2 years (P = 0.03). Albuminuria normalized in 37.5% (6/16) after 1 year and 61% (8/13) after 2 years of HU therapy. Among those without albuminuria prior to HU, 13% (6/47) developed albuminuria during HU therapy. Sixteen percent (13/80) of control patients had albuminuria in the beginning of study period, which normalized in 15% (two of 13) of patients at 1-year follow up. Introduction of HU is associated with significant decreases in urine ACR in children with SCD and albuminuria. © 2017 Wiley Periodicals, Inc.

SU-F-J-172: Hybrid MR/CT Compatible Phantom for MR-Only Based Radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kim, M; Lee, S; Song, K

2016-06-15

Purpose: Development of hybrid MR/CT compatible phantom was introduced to fully establish MR image only radiation treatment and this suggested technique using in-house developed hybrid MR/CT compatible phantom image would utilize to generate radiation treatment planning and perform dose calculation without multi-modal registration process or generation of pseudo CT. Methods: Fundamental characteristics for “hybrid MR/CT compatible phantom” was established: Relaxation times equivalent to human tissue, dielectric properties, homogeneous relaxation times, sufficient strength to fabricate a torso, ease of handling, a wide variety of density material for calibration, chemical and physical stability over an extended time. For this requirements, chemical componentmore » in each tested plug which would be tissue equivalent to human tissue on MR and CT image and production of phantom body and plug was performed. Chemical component has described below: Agaros, GdCl{sub 3}, NaN{sub 3}, NaCl, K{sub 2}Co{sub 3}, deionized-distilled water. Various mixture of chemical component to simulate human tissue on both MR and CT image was tested by measuring T1, T2 relaxation time and signal intensity (SI) on MR image and Hounsfield unit (HU) on CT and each value was compared. The hybrid MR/CT compatible phantom with 14 plugs was designed and has made. Total height and external diameter was decided by internal size of 32 channel MR head-coil. Results: Tissue-equivalent chemical component materials and hybrid MR/CT compatible phantom was developed. The range of T1, T2 relaxation time and SI on MR image, HU on CT was acquired and could be adjusted to correspond to simulated human tissue. Conclusion: Current result shows its possibility for MR-only based radiotherapy and the best mixing rate of chemical component for tissue-equivalent image on MR and CT was founded. However, additional technical issues remain to be overcome. Conversion of SI on MR image into HU and dose calculation based on converted MRI will be progressing.« less

The induced RNA-binding protein, HuR, targets 3'-UTR region of IL-6 mRNA and enhances its stabilization in periodontitis.

PubMed

Ouhara, K; Munenaga, S; Kajiya, M; Takeda, K; Matsuda, S; Sato, Y; Hamamoto, Y; Iwata, T; Yamasaki, S; Akutagawa, K; Mizuno, N; Fujita, T; Sugiyama, E; Kurihara, H

2018-06-01

RNA-binding proteins (RBPs) regulate mRNA stability by binding to the 3'-untranslated region (UTR) region of mRNA. Human antigen-R (HuR), one of the RBPs, is involved in the progression of diseases, such as rheumatoid arthritis, diabetes mellitus and some inflammatory diseases. Interleukin (IL)-6 is a major inflammatory cytokine regulated by HuR binding to mRNA. Periodontal disease (PD) is also an inflammatory disease caused by elevations in IL-6 following an infection by periodontopathogenic bacteria. The involvement of HuR in the progression of PD was assessed using in-vitro and in-vivo experiments. Immunohistochemistry of inflamed periodontal tissue showed strong staining of HuR in the epithelium and connective tissue. HuR mRNA and protein level was increased following stimulation with Porphyromonas gingivalis (Pg), one of the periodontopathogenic bacteria, lipopolysacchride (LPS)-derived from Pg (PgLPS) and tumour necrosis factor (TNF)-α in OBA-9, an immortalized human gingival epithelial cell. The luciferase activity of 3'-UTR of IL-6 mRNA was increased by TNF-α, Pg and PgLPS in OBA-9. Luciferase activity was also increased in HuR-over-expressing OBA-9 following a bacterial stimulation. Down-regulation of HuR by siRNA resulted in a decrease in mRNA expression and production of IL-6. In contrast, the over-expression of HuR increased IL-6 mRNA expression and production in OBA-9. The HuR inhibitor, quercetin, suppressed Pg-induced HuR mRNA expression and IL-6 production in OBA-9. An oral inoculation with quercetin also inhibited bone resorption in ligature-induced periodontitis model mice as a result of down-regulation of IL-6. These results show that HuR modulates inflammatory responses by regulating IL-6. © 2018 British Society for Immunology.

Silencing expression of UO-44 (CUZD1) using small interfering RNA sensitizes human ovarian cancer cells to cisplatin in vitro.

PubMed

Leong, C T C; Ong, C K; Tay, S K; Huynh, H

2007-02-08

Ovarian cancer is currently the second leading cause of gynecological malignancy and cisplatin or cisplatin-based regimens have been the standard of care for the treatment of advance epithelial ovarian cancers. However, the efficacy of cisplatin treatment is often limited by the development of drug resistance either through the inhibition of apoptotic genes or activation of antiapoptotic genes. We have previously reported the overexpression of human UO-44 (HuUO-44) in ovarian cancers and the HuUO-44 antisera markedly inhibited NIH-OVCAR3 ovarian cancer cell attachment and proliferation (Oncogene 23: 5707-5718, 2004). In the present study, we observed through the cancer cell line profiling array that the expression of HuUO-44 was suppressed in the ovarian cancer cell line (SKOV-3) after treatment with several chemotherapeutic drugs. Similarly, this suppression in HuUO-44 expression was also correlated to the cisplatin sensitivity in two other ovarian cancer cell lines NIH-OVCAR3 and OV-90 in a dose-dependent manner. To elucidate the function of HuUO-44 in cisplatin chemoresistance in ovarian cancer cell, small interfering RNAs (siRNAs) were employed to mediate HuUO-44 silencing in ovarian cancer cell line, NIH-OVCAR3. HuUO-44 RNA interference (RNAi) resulted in the inhibition of cell growth and proliferation. Importantly, HuUO-44 RNAi significantly increased sensitivity of NIH-OVCAR3 to cytotoxic stress induced by cisplatin (P<0.01). Strikingly, we have also demonstrated that overexpression of HuUO-44 significantly conferred cisplatin resistance in NIH-OVCAR3 cells (P<0.05). Taken together, UO-44 is involved in conferring cisplatin resistance; the described HuUO-44-specific siRNA oligonucleotides that can potently silence HuUO-44 gene expression may prove to be valuable pretreatment targets for antitumor therapy or other pathological conditions that involves aberrant HuUO-44 expression.

The heterodimeric structure of heterogeneous nuclear ribonucleoprotein C1/C2 dictates 1,25-dihydroxyvitamin D-directed transcriptional events in osteoblasts.

PubMed

Lisse, Thomas S; Vadivel, Kanagasabai; Bajaj, S Paul; Chun, Rene F; Hewison, Martin; Adams, John S

2014-01-01

Heterogeneous nuclear ribonucleoprotein (hnRNP) C plays a key role in RNA processing. More recently hnRNP C has also been shown to function as a DNA binding protein exerting a dominant-negative effect on transcriptional responses to the vitamin D hormone,1,25-dihydroxyvitamin D (1,25(OH) 2 D), via interaction in cis with vitamin D response elements (VDREs). The physiologically active form of human hnRNPC is a tetramer of hnRNPC1 (huC1) and C2 (huC2) subunits known to be critical for specific RNA binding activity in vivo , yet the requirement for heterodimerization of huC1 and C2 in DNA binding and downstream action is not well understood. While over-expression of either huC1 or huC2 alone in mouse osteoblastic cells did not suppress 1,25(OH) 2 D-induced transcription, over-expression of huC1 and huC2 in combination using a bone-specific polycistronic vector successfully suppressed 1,25(OH) 2 D-mediated induction of osteoblast target gene expression. Over-expression of either huC1 or huC2 in human osteoblasts was sufficient to confer suppression of 1,25(OH) 2 D-mediated transcription, indicating the ability of transfected huC1 and huC2 to successfully engage as heterodimerization partners with endogenously expressed huC1 and huC2. The failure of the chimeric combination of mouse and human hnRNPCs to impair 1,25(OH) 2 D-driven gene expression in mouse cells was structurally predicted, owing to the absence of the last helix in the leucine zipper (LZ) heterodimerization domain of hnRNPC gene product in lower species, including the mouse. These results confirm that species-specific heterodimerization of hnRNPC1 and hnRNPC2 is a necessary prerequisite for DNA binding and down-regulation of 1,25(OH) 2 D-VDR-VDRE-directed gene transactivation in osteoblasts.

Estrous Cyclicity of Mice During Simulated Weightlessness

NASA Technical Reports Server (NTRS)

Moyer, Eric; Talyansky, Yuli; Scott, Ryan; Tash, Joseph; Christenson, Lane; Alwood, Joshua; Ronca, April

2017-01-01

Hindlimb unloading (HU) is a rodent model system used to simulate weightlessness experienced in space. However, some effects of this approach on rodent physiology are under-studied, specifically the effects on ovarian estrogen production which drives the estrous cycle. To resolve this deficiency, we conducted a ground-based validation study using the HU model, while monitoring estrous cycles in 16-weeks-old female C57BL6 mice. Animals were exposed to HU for 12 days following a 3 day HU cage acclimation period, and estrous cycling was analyzed in HU animals (n22), normally loaded HU Cage Pair-Fed controls (CPF; n22), and Vivarium controls fed ad libitum (VIV; n10). Pair feeding was used to control for potential nutritional deficits on ovarian function. Vaginal cells were sampled daily in all mice via saline lavage. Cells were dried and stained with crystal violet, and the smears evaluated using established vaginal cytology techniques by two individuals blinded to the animal treatment group. Estrous cyclicity was disrupted in nearly all HU and CPF mice, while those maintained in VIV had an average normal cycle length of 4.8 0.5 days, with all stages in the cycle visibly observed. CPF and HU animals arrested in the diestrous phase, which precedes the pre-ovulatory estrogen surge. Additionally, infection-like symptoms characterized by vaginal discharge and swelling arose in several HU animals, which we suspect was due to an inability of these mice to properly groom themselves, andor due to the change in the gravity vector relative to the vaginal opening, which prevented drainage of the lavage solution. Pair-feeding resulted in similar weight gains of HU and CPF (1.5 vs 3.0, respectively). The current results indicate that pair-feeding controlled weight gain and that the HU cage alone influenced estrous cyclicity. Thus, longer acclimation needs to be tested to determine if and when normal estrous cycling resumes in non-loaded mice in HU cages prior to HU testing. Future studies might also examine whether modifications to the vaginal lavage procedure might prevent the onset of the infection-like symptoms, and allow estrous cyclicity to be measured in this model system.

Impact of divergent selection for ultimate pH of pectoralis major muscle on biochemical, histological, and sensorial attributes of broiler meat.

PubMed

Alnahhas, N; Le Bihan-Duval, E; Baéza, E; Chabault, M; Chartrin, P; Bordeau, T; Cailleau-Audouin, E; Meteau, K; Berri, C

2015-09-01

The impact of divergent selection based on the ultimate pH (pHu) of pectoralis major (P. major) muscle on the chemical, biochemical, and histological profiles of the muscle and sensorial quality of meat was investigated in broiler chickens. The protein, lipid, DM, glycogen and lactate content, glycolytic potential, proteolysis, lipid and protein oxidation index, muscle fiber cross-sectional area, capillary density, and collagen surface were determined on the breast P. major muscle of 6-wk-old broilers issued from the high-pHu (pHu+) and low-pHu (pHu-) lines. Sensory attributes were also evaluated on the breast (roasted or grilled) and thigh (roasted) meat of the 2 lines. Protein, lipid, and DM content of P. major muscle were not affected by selection ( > 0.05). However, the P. major muscle of the pHu+ line was characterized by lower residual glycogen (-16%; ≤ 0.001) and lactate (-14%; ≤ 0.001) content and lower glycolytic potential (-14%; ≤ 0.001) compared with the pHu- line. Although the average cross-sectional area of muscle fibers and surface occupied by collagen were similar ( > 0.05) in both lines, fewer capillaries per fiber (-15%; ≤ 0.05) were observed in the pHu+ line. The pHu+ line was also characterized by lower lipid oxidation (thiobarbituric acid reactive substance index: -23%; ≤ 0.05) but protein oxidation and proteolysis index were not different ( > 0.05) between the 2 lines. At the sensory level, selection on breast muscle pHu mainly affected the texture of grilled and roast breast meat, which was judged significantly more tender ( ≤ 0.001) in the pHu+ line, and the acid taste, which was less pronounced in the roasted breast meat of the pHu+ line ( ≤ 0.002). This study highlighted that selection based on pHu does not affect the chemical composition and structure of breast meat. However, by modifying muscle blood supply and glycogen turnover, it affects meat acidity and oxidant status, both of which are likely to contribute to the large differences in texture observed between the 2 lines.

Optimization of coronary attenuation in coronary computed tomography angiography using diluted contrast material.

PubMed

Kawaguchi, Naoto; Kurata, Akira; Kido, Teruhito; Nishiyama, Yoshiko; Kido, Tomoyuki; Miyagawa, Masao; Ogimoto, Akiyoshi; Mochizuki, Teruhito

2014-01-01

The purpose of this study was to evaluate a personalized protocol with diluted contrast material (CM) for coronary computed tomography angiography (CTA). One hundred patients with suspected coronary artery disease underwent retrospective electrocardiogram-gated coronary CTA on a 256-slice multidetector-row CT scanner. In the diluted CM protocol (n=50), the optimal scan timing and CM dilution rate were determined by the timing bolus scan, with 20% CM dilution (5ml/s during 10s) being considered suitable to achieve the target arterial attenuation of 350 Hounsfield units (HU). In the body weight (BW)-adjusted protocol (n=50, 222mg iodine/kg), only the optimal scan timing was determined by the timing bolus scan. The injection rate and volume in the timing bolus scan and real scan were identical between the 2 protocols. We compared the means and variations in coronary attenuation between the 2 protocols. Coronary attenuation (mean±SD) in the diluted CM and BW-adjusted protocols was 346.1±23.9 HU and 298.8±45.2 HU, respectively. The diluted CM protocol provided significantly higher coronary attenuation and lower variance than did the BW-adjusted protocol (P<0.05, in each). The diluted CM protocol facilitates more uniform attenuation on coronary CTA in comparison with the BW-adjusted protocol.  

Predictive validity of preoperative CT scans and the risk of pedicle screw loosening in spinal surgery.

PubMed

Bredow, Jan; Boese, C K; Werner, C M L; Siewe, J; Löhrer, L; Zarghooni, K; Eysel, P; Scheyerer, M J

2016-08-01

Pedicle screw fixation is the standard technique for the stabilization of the spine, a clinically relevant complication of which is screw loosening. This retrospective study investigates whether preoperative CT scanning can offer a predictor of screw loosening. CT-scan attenuation in 365 patients was evaluated to determine the mean bone density of each vertebral body. Screw loosening or dislocation was determined in CT scans postoperatively using the standard radiological criteria. Forty-five of 365 patients (12.3 %; 24 male, 21 female) suffered postoperative screw loosening (62 of 2038 screws) over a mean follow-up time of 50.8 months. Revision surgeries were necessary in 23 patients (6.3 %). The correlation between decreasing mean CT attenuation in Hounsfield Units (HU) and increasing patient age was significant (p < 0.001). Mean bone density was 116.3 (SD 53.5) HU in cases with screw loosening and 132.7 (SD 41.3) HU in cases in which screws remained fixed. The difference was statistically significant (p = 0.003). The determination of bone density with preoperative CT scanning can predict the risk of screw loosening and inform the decision to use cement augmentation to reduce the incidence of screw loosening.

Preliminary evaluation of the dosimetric accuracy of cone-beam computed tomography for cases with respiratory motion

NASA Astrophysics Data System (ADS)

Kim, Dong Wook; Bae, Sunhyun; Chung, Weon Kuu; Lee, Yoonhee

2014-04-01

Cone-beam computed tomography (CBCT) images are currently used for patient positioning and adaptive dose calculation; however, the degree of CBCT uncertainty in cases of respiratory motion remains an interesting issue. This study evaluated the uncertainty of CBCT-based dose calculations for a moving target. Using a phantom, we estimated differences in the geometries and the Hounsfield units (HU) between CT and CBCT. The calculated dose distributions based on CT and CBCT images were also compared using a radiation treatment planning system, and the comparison included cases with respiratory motion. The geometrical uncertainties of the CT and the CBCT images were less than 0.15 cm. The HU differences between CT and CBCT images for standard-dose-head, high-quality-head, normal-pelvis, and low-dose-thorax modes were 31, 36, 23, and 33 HU, respectively. The gamma (3%, 0.3 cm)-dose distribution between CT and CBCT was greater than 1 in 99% of the area. The gamma-dose distribution between CT and CBCT during respiratory motion was also greater than 1 in 99% of the area. The uncertainty of the CBCT-based dose calculation was evaluated for cases with respiratory motion. In conclusion, image distortion due to motion did not significantly influence dosimetric parameters.

Iodine concentration calculated by dual-energy computed tomography (DECT) as a functional parameter to evaluate thyroid metabolism in patients with hyperthyroidism.

PubMed

Binh, Duong Duc; Nakajima, Takahito; Otake, Hidenori; Higuchi, Tetsuya; Tsushima, Yoshito

2017-07-19

Thyroid function in patients with Grave's disease is usually evaluated by thyroid scintigraphy with radioactive iodine. Recently, dual-energy computed tomography (DECT) with two different energy X-rays can calculate iodine concentrations and can be applied for iodine measurements in thyroid glands. This study aimed to assess the potential use of DECT for the functional assessment of the thyroid gland. Thirteen patients with Grave's disease treated at our hospital from May to September 2015 were included in this retrospective study. Before treatments, all subjects had undergone both iodine scintigraphy [three and 24 h after oral administration of 123 I (20 μCi)] and non-enhanced DECT. The region of interests (ROIs) were placed in both lobes of the thyroid glands, and CT values (HU: Hounsfield unit) and iodine concentrations (mg/mL) calculated from DECT images were measured. The correlation between CT values and iodine concentrations from DECT in the thyroid gland was evaluated and then the iodine concentrations were compared with radioactive iodine uptake ratios by thyroid scintigraphy. Mean (±SD) 123 I uptake increased from 46.3 (±22.2) % (range, 11.1-80.1) at 3 h, to 66.5 (±15.2) % (range, 40.0-86.1) at 24 h (p < 0.01). CT values ranged from 34.5 to 98.7 HU [mean: 67.8 (±18.6)], while the iodine concentrations calculated with DECT ranged from 0.0 to 1.3 mg/mL [mean: 0.5 (±0.4)]. A moderate positive correlation between CT values and the calculated iodine concentrations in the thyroid gland was seen (R = 0.429, p < 0.05). A significant negative correlation between 123 I uptake at 3 h and iodine concentration by DECT were seen (R = -0.680, p < 0.05), although no correlation was observed between 123 I uptake at 3 h and CT values (p = 0.087). No correlation was observed between 123 I uptake at 24 h and CT values (p = 0.153) or that between 123 I uptake at 24 h and iodine concentration by DECT (p = 0.073). The negative correlation of 123 I uptake at 3 h with iodine concentration evaluated by DECT was better than that observed with simple CT value. DECT may have a potential role in the evaluation of iodine turnover in hyperthyroid patients.

Paramagnetic nanoparticles to track and quantify in vivo immune human therapeutic cells

NASA Astrophysics Data System (ADS)

Aspord, Caroline; Laurin, David; Janier, Marc F.; Mandon, Céline A.; Thivolet, Charles; Villiers, Christian; Mowat, Pierre; Madec, Anne-Marie; Tillement, Olivier; Perriat, Pascal; Louis, Cédric; Bérard, Frédéric; Marche, Patrice N.; Plumas, Joël; Billotey, Claire

2013-11-01

This study aims to investigate gadolinium-based nanoparticles (Gd-HNP) for in vitro labeling of human plasmacytoid dendritic cells (HuPDC) to allow for in vivo tracking and HuPDC quantifying using magnetic resonance imaging (MRI) following parenteral injection. Human plasmacytoid DC were labeled (LabHuPDC) with fluorescent Gd-HNP (Gd-FITC-HNP) and injected via intraperitoneal and intravenous routes in 4-5 NOD-SCID β2m-/-mice (treated mice = TM). Control mice (CM) were similarly injected with unlabeled HuPDC. In vivo 7 T MRI was performed 24 h later and all spleens were removed in order to measure Gd and fluorescence contents and identify HuPDC. Gd-FITC-HNP efficiently labeled HuPDC (0.05 to 0.1 pg per cell), without altering viability and activation properties. The magnetic resonance (MR) signal was exclusively due to HuPDC. The normalized MR splenic intensity for TM was significantly higher than for CM (p < 0.024), and highly correlated with the spleen Gd content (r = 0.97), and the number of HuPDC found in the spleen (r = 0.94). Gd-FITC-HNP allowed for in vivo tracking and HuPDC quantifying by means of MRI following parenteral injection, with very high sensitivity (<3000 cells per mm3). The safety of these new nanoparticle types must be confirmed via extensive toxicology tests including in vivo stability and biodistribution studies.This study aims to investigate gadolinium-based nanoparticles (Gd-HNP) for in vitro labeling of human plasmacytoid dendritic cells (HuPDC) to allow for in vivo tracking and HuPDC quantifying using magnetic resonance imaging (MRI) following parenteral injection. Human plasmacytoid DC were labeled (LabHuPDC) with fluorescent Gd-HNP (Gd-FITC-HNP) and injected via intraperitoneal and intravenous routes in 4-5 NOD-SCID β2m-/-mice (treated mice = TM). Control mice (CM) were similarly injected with unlabeled HuPDC. In vivo 7 T MRI was performed 24 h later and all spleens were removed in order to measure Gd and fluorescence contents and identify HuPDC. Gd-FITC-HNP efficiently labeled HuPDC (0.05 to 0.1 pg per cell), without altering viability and activation properties. The magnetic resonance (MR) signal was exclusively due to HuPDC. The normalized MR splenic intensity for TM was significantly higher than for CM (p < 0.024), and highly correlated with the spleen Gd content (r = 0.97), and the number of HuPDC found in the spleen (r = 0.94). Gd-FITC-HNP allowed for in vivo tracking and HuPDC quantifying by means of MRI following parenteral injection, with very high sensitivity (<3000 cells per mm3). The safety of these new nanoparticle types must be confirmed via extensive toxicology tests including in vivo stability and biodistribution studies. Corresponding address: Service de Médecine Nucléaire, Hôpital, Nord - CHU Saint-Etienne, Avenue Albert Raimond, 42270 Saint-Priest-en-Jarez, France. E-mail: claire.billotey@chu-st-etienne.fr

Quantifying metal artefact reduction using virtual monochromatic dual-layer detector spectral CT imaging in unilateral and bilateral total hip prostheses.

PubMed

Wellenberg, R H H; Boomsma, M F; van Osch, J A C; Vlassenbroek, A; Milles, J; Edens, M A; Streekstra, G J; Slump, C H; Maas, M

2017-03-01

To quantify the impact of prosthesis material and design on the reduction of metal artefacts in total hip arthroplasties using virtual monochromatic dual-layer detector Spectral CT imaging. The water-filled total hip arthroplasty phantom was scanned on a novel 128-slice Philips IQon dual-layer detector Spectral CT scanner at 120-kVp and 140-kVp at a standard computed tomography dose index of 20.0mGy. Several unilateral and bilateral hip prostheses consisting of different metal alloys were inserted and combined which were surrounded by 18 hydroxyapatite calcium carbonate pellets representing bone. Images were reconstructed with iterative reconstruction and analysed at monochromatic energies ranging from 40 to 200keV. CT numbers in Hounsfield Units (HU), noise measured as the standard deviation in HU, signal-to-noise-ratios (SNRs) and contrast-to-noise-ratios (CNRs) were analysed within fixed regions-of-interests placed in and around the pellets. In 70 and 74keV virtual monochromatic images the CT numbers of the pellets were similar to 120-kVp and 140-kVp polychromatic results, therefore serving as reference. A separation into three categories of metal artefacts was made (no, mild/moderate and severe) where pellets were categorized based on HU deviations. At high keV values overall image contrast was reduced. For mild/moderate artefacts, the highest average CNRs were attained with virtual monochromatic 130keV images, acquired at 140-kVp. Severe metal artefacts were not reduced. In 130keV images, only mild/moderate metal artefacts were significantly reduced compared to 70 and 74keV images. Deviations in CT numbers, noise, SNRs and CNRs due to metal artefacts were decreased with respectively 64%, 57%, 62% and 63% (p<0.001) compared to unaffected pellets. Optimal keVs, based on CNRs, for different unilateral and bilateral metal hip prostheses consisting of different metal alloys varied from 74 to 150keV. The Titanium alloy resulted in less severe artefacts and were reduced more effectively compared to the Cobalt alloy. Virtual monochromatic dual-layer Spectral CT imaging results in a significant reduction of streak artefacts produced by beam-hardening in mild and moderate artefacts by improving CT number accuracy, SNRs and CNRs, while decreasing noise values in a total hip arthroplasty phantom. An optimal monochromatic energy of 130keV was found ranging from 74keV to 150keV for different unilateral and bilateral hip prostheses consisting of different metal alloys. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

Dynamic iterative beam hardening correction (DIBHC) in myocardial perfusion imaging using contrast-enhanced computed tomography.

PubMed

Stenner, Philip; Schmidt, Bernhard; Allmendinger, Thomas; Flohr, Thomas; Kachelrie, Marc

2010-06-01

In cardiac perfusion examinations with computed tomography (CT) large concentrations of iodine in the ventricle and in the descending aorta cause beam hardening artifacts that can lead to incorrect perfusion parameters. The aim of this study is to reduce these artifacts by performing an iterative correction and by accounting for the 3 materials soft tissue, bone, and iodine. Beam hardening corrections are either implemented as simple precorrections which cannot account for higher order beam hardening effects, or as iterative approaches that are based on segmenting the original image into material distribution images. Conventional segmentation algorithms fail to clearly distinguish between iodine and bone. Our new algorithm, DIBHC, calculates the time-dependent iodine distribution by analyzing the voxel changes of a cardiac perfusion examination (typically N approximately 15 electrocardiogram-correlated scans distributed over a total scan time up to T approximately 30 s). These voxel dynamics are due to changes in contrast agent. This prior information allows to precisely distinguish between bone and iodine and is key to DIBHC where each iteration consists of a multimaterial (soft tissue, bone, iodine) polychromatic forward projection, a raw data comparison and a filtered backprojection. Simulations with a semi-anthropomorphic dynamic phantom and clinical scans using a dual source CT scanner with 2 x 128 slices, a tube voltage of 100 kV, a tube current of 180 mAs, and a rotation time of 0.28 seconds have been carried out. The uncorrected images suffer from beam hardening artifacts that appear as dark bands connecting large concentrations of iodine in the ventricle, aorta, and bony structures. The CT-values of the affected tissue are usually underestimated by roughly 20 HU although deviations of up to 61 HU have been observed. For a quantitative evaluation circular regions of interest have been analyzed. After application of DIBHC the mean values obtained deviate by only 1 HU for the simulations and the corrected values show an increase of up to 61 HU for the measurements. One iteration of DIBHC greatly reduces the beam hardening artifacts induced by the contrast agent dynamics (and those due to bone) now allowing for an improved assessment of contrast agent uptake in the myocardium which is essential for determining myocardial perfusion.

Association of Changes in Abdominal Fat and Cardiovascular Risk Factors

PubMed Central

Lee, Jane J.; Pedley, Alison; Hoffmann, Udo; Massaro, Joseph M.; Fox, Caroline S.

2017-01-01

BACKGROUND Subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) are associated with adverse cardiometabolic risk profiles. OBJECTIVES This study explored the degree to which changes in abdominal fat quantity and quality are associated with changes in cardiovascular disease (CVD) risk factors. METHODS Study participants (n = 1,106; 44.1% women; mean baseline age 45.1 years) were drawn from the Framingham Heart Study Third Generation cohort who participated in the computed tomography (CT) substudy Exams 1 and 2. Participants were followed for 6.1 years on average. Abdominal adipose tissue volume in cm3 and attenuation in Hounsfield units (HU) were determined by CT-acquired abdominal scans. RESULTS The mean fat volume change was an increase of 602 cm3 for SAT and an increase of 703 cm3 for VAT; the mean fat attenuation change was a decrease of 5.5HU for SAT and an increase of 0.07 HU for VAT. An increase in fat volume and decrease in fat attenuation were associated with adverse changes in CVD risk factors. An additional 500 cm3 increase in fat volume was associated with incident hypertension (odds ratio [OR]: 1.21 for SAT; OR: 1.30 for VAT), hypertriglyceridemia (OR: 1.15 for SAT; OR: 1.56 for VAT), and metabolic syndrome (OR: 1.43 for SAT; OR: 1.82 for VAT; all p < 0.05). Similar trends were observed for each additional 5 HU decrease in abdominal adipose tissue attenuation. Most associations remained significant even after further accounting for body mass index change, waist circumference change, or respective abdominal adipose tissue volumes. CONCLUSIONS Increasing accumulation of fat quantity and decreasing fat attenuation are associated with worsening of CVD risk factors beyond the associations with generalized adiposity, central adiposity, or respective adipose tissue volumes. PMID:27687192

Biological impact of α genes, β haplotypes, and G6PD activity in sickle cell anemia at baseline and with hydroxyurea

PubMed Central

Arnaud, Cécile; Kamdem, Annie; Hau, Isabelle; Lelong, Françoise; Epaud, Ralph; Pondarré, Corinne; Pissard, Serge

2018-01-01

Sickle cell anemia (SCA), albeit monogenic, has heterogeneous phenotypic expression, mainly related to the level of hemoglobin F (HbF). No large cohort studies have ever compared biological parameters in patients with major β-globin haplotypes; ie, Senegal (SEN), Benin (BEN), and Bantu/Central African Republic (CAR). The aim of this study was to evaluate the biological impact of α genes, β haplotypes, and glucose-6-phosphate dehydrogenase (G6PD) activity at baseline and with hydroxyurea (HU). Homozygous HbS patients from the Créteil pediatric cohort with available α-gene and β-haplotype data were included (n = 580; 301 females and 279 males) in this retrospective study. Homozygous β-haplotype patients represented 74% of cases (37.4% CAR/CAR, 24.3% BEN/BEN, and 12.1% SEN/SEN). HU was given to 168 cohort SCA children. Hematological parameters were recorded when HbF was maximal, and changes (ΔHU-T0) were calculated. At baseline, CAR-haplotype and α-gene numbers were independently and negatively correlated with Hb and positively correlated with lactate dehydrogenase. HbF was negatively correlated with CAR-haplotype numbers and positively with BEN- and SEN-haplotype numbers. The BCL11A/rs1427407 “T” allele, which is favorable for HbF expression, was positively correlated with BEN- and negatively correlated with CAR-haplotype numbers. With HU treatment, Δ and HbF values were positively correlated with the BEN-haplotype number. BEN/BEN patients had higher HbF and Hb levels than CAR/CAR and SEN/SEN patients. In conclusion, we show that BEN/BEN patients have the best response on HU and suggest that this could be related to the higher prevalence of the favorable BCL11A/rs1427407/T/allele for HbF expression in these patients. PMID:29555644

High-Pitch Coronary CT Angiography at 70 kVp Adopting a Protocol of Low Injection Speed and Low Volume of Contrast Medium

PubMed Central

Feng, Ruiqi; Tong, Jiajie; Liu, Xiaofei; Zhao, Yu

2017-01-01

Objective To evaluate the feasibility and image quality (IQ) of prospectively high-pitch coronary CT angiography (CCTA) with low contrast medium injection rate at 70 kVp. Materials and Methods One hundred and four patients with suspected coronary artery disease (body mass index < 26 kg/m2, sinus rhythm and heart rate < 70 beats/min) were prospectively enrolled and randomly divided into two groups. In group A and group B, 28 mL and 40 mL of 370 mgI/mL iodinated contrast media was administrated at a flow rate of 3.5 and 5 mL/s, respectively. CT values, noise, signal-to-noise ratio, contrast-to-noise ratio (CNR) of the proximal segments of coronary arteries and subjective IQ were evaluated. Results The CT values and noise in group A were significantly lower than those in group B (434–485 Hounsfield units [HU] vs. 772–851 HU, all p < 0.001; 17.8–22.3 vs. 23.3–26.4, all p < 0.005). The CNRs of the right coronary artery and left main artery showed no statistical difference between the two groups (42.1 ± 13.8 vs. 36.8 ± 16.0, p = 0.074; 38.7 ± 10.6 vs. 38.1 ± 17.0, p = 0.819). No statistical difference was observed between the two groups in IQ scores (3.04 ± 0.75 vs. 3.0 ± 0.79, p = 0.526) and diagnostic ratio (96.1% [50/52] vs. 94.2% [49/52], p = 0.647). Conclusion Prospective high-pitch CCTA at 70 kVp with 28 mL of contrast media and injection rate of 3.5 mL/s could provide diagnostic IQ for normal-weight patients with heart rate of < 70 beats/min. PMID:28860894

Computed Tomography Demonstration of the Production and Distribution of Oxygen Gas Following Intratumoral Injection of a New Radiosensitizer (KORTUC) for Patients with Breast Cancer-Is Intratumoral Injection Not an Ideal Approach to Solve the Major Problem of Tumor Hypoxia in Radiotherapy?

PubMed

Hayashi, Naoya; Ogawa, Yasuhiro; Kubota, Kei; Okino, Kazuhiro; Akima, Ryo; Morita-Tokuhiro, Shiho; Tsuzuki, Akira; Yaogawa, Shin; Nishioka, Akihito; Miyamura, Mitsuhiko

2016-04-01

We previously developed a new enzyme-targeting radiosensitization treatment named Kochi Oxydol-Radiation Therapy for Unresectable Carcinomas, Type II (KORTUC II), which contains hydrogen peroxide and sodium hyaluronate for injection into various types of tumors. For breast cancer treatment, the radiosensitization agent was injected into the tumor tissue twice a week under ultrasonographic guidance, immediately prior to each administration of radiation therapy. At approximately three hours after the second or third injection, computed tomography (CT) was performed to confirm the production and distribution of oxygen gas generated from the KORTUC radiosensitization agent by catalysis of peroxidases contained mainly in tumor tissue. The purpose of this study was to demonstrate that tumor hypoxia could be overcome by such a procedure and to evaluate the method of intratumoral injection in terms of confirming oxygen distribution in the target tumor tissue and around the tumor to be visualized on dedicated CT imaging. Three-dimensional reconstructed maximum intensity projection imaging of contrast-enhanced breast magnetic resonance imaging was used to compare the position of the tumor and that of the generated oxygen. Distributed oxygen gas was confirmed in the tumor tissue and around it in all 10 patients examined in the study. A region of oxygen gas was measured as an average value of -457.2 Hounsfield units (HU) as a region of interest. A slightly increased HU value compared to the density of air or oxygen was considered due to the presence of tumor tissue in the low-density area on 5-mm-thick reconstructed CT imaging. The results of this study showed that intratumoral oxygen was successfully produced by intratumoral KORTUC injection under ultrasonographic guidance, and that tumor hypoxia, which is considered a main cause of radioresistance in currently used Linac (linear accelerator) radiation therapy for malignant neoplasms, could be resolved by this method.

Efficacy of various protein-based coating on enhancing the shelf life of fresh eggs during storage.

PubMed

Caner, Cengiz; Yüceer, Muhammed

2015-07-01

The effectiveness of various coatings (whey protein isolate [WPI], whey protein concentrate [WPC], zein, and shellac) on functional properties, interior quality, and eggshell breaking strength of fresh eggs were evaluated during storage at 24 °: C for 6 weeks. Coatings and storage time had significant effects on Haugh unit, yolk index, albumen pH, dry matter (DMA), relative whipping capacity (RWC), and albumen viscosity. Uncoated eggs had higher albumen pH (9.56) and weight loss, and lower albumen viscosity (5.73), Haugh unit (HU), and yolk index (YI) during storage. Among the coated eggs, the shellac and zein coated eggs had the highest value of albumen viscosity (27.26 to 26.90), HU (74.10 to 73.61), and YI (44.84 to 44.63) after storage. Shellac (1.44%) was more effective in preventing weight loss than WPC (4.59%), WPI (4.60%), and zein (2.13%) coatings. Uncoated eggs had the higest value (6.71%) of weight lost. All coatings increased shell strength (5.18 to 5.73 for top and 3.58 to 4.71 for bottom) significantly (P < 0.05) compared to the uncoated eggs (4.70 for top and 3.15 for bottom). The functional properties such as albumen DMA (14.50 to 16.66 and 18.97 for uncoated) and albumen RWC (841 to 891 and 475 for uncoated) of fresh eggs can be preserved during storage when they are coated. The shellac and zein coatings were more effective for maintaining the internal quality of fresh eggs during storage. Fourier transform near infrared (FT-NIR) in the 800 to 2500 nm reflection spectra were used to quantify the contents of the fresh eggs at the end of storage. Eggs coated with shellac or zein displayed a higher absorbance at 970 and 1,197 nm respectively (OH vibration of water) compared with those coated with WPI or WPC and the uncoated group at the end of storage. The coatings improved functional properties and also shell strength and could be a viable alternative technology for maintaining the internal quality of eggs during long-term storage. This study highlights the promising use of various coatings to both enhance the functional properties and to reduce the breakage of eggs. © 2015 Poultry Science Association Inc.

Occurrence of chai hu (Bupleuri radix) in prescriptions of Chinese herbal medicine in Switzerland.

PubMed

Klein, Sabine D; Becker, Simon; Wolf, Ursula

2012-01-01

Chai hu (Bupleuri radix), one of the most frequently used herbs in Chinese herbal medicine, has 3 major functions, depending on dosage and combination with other herbs. The aim of this study was to investigate how chai hu is prescribed in everyday practice in Switzerland, and whether these prescription patterns reflect its various applications. A random sample of 1,053 prescriptions was drawn from the database of Lian Chinaherb AG, Wollerau, Switzerland, and analyzed regarding the most frequently used classical formulas containing chai hu, daily dosages and combinations with other herbs. 29.0% of all prescriptions contained chai hu, and 98.0% of these were in granular form. The most frequently used classical formulas were xiao yao san ('rambling powder'), jia wei xiao yao san ('augmented rambling powder') and chai hu shu gan san ('Bupleurum powder to spread the liver'). In more than half of the prescriptions, chai hu was combined with bai shao (Paeoniae Radix Alba), dang gui (Angelicae sinensis radix) or fu ling (Poria). 51.8% of the prescriptions contained a low daily dosage of chai hu, 24.9% a medium and 15.1% a high dosage. Chai hu was generally prescribed in classic combinations with other herbs and in a medium dosage. Due to the addition of supplementary herbs to classical formulas, its daily dose was often diminished from a high or medium dose to a low dose. This raises the question if chai hu would then still exert its desired function of, e.g., moving liver-qi in these prescriptions.

Pharmacokinetics and bioequivalence of a liquid formulation of hydroxyurea in children with sickle cell anemia.

PubMed

Estepp, Jeremie H; Melloni, Chiara; Thornburg, Courtney D; Wiczling, Paweł; Rogers, Zora; Rothman, Jennifer A; Green, Nancy S; Liem, Robert; Brandow, Amanda M; Crary, Shelley E; Howard, Thomas H; Morris, Maurine H; Lewandowski, Andrew; Garg, Uttam; Jusko, William J; Neville, Kathleen A

2016-03-01

Hydroxyurea (HU) is a crucial therapy for children with sickle cell anemia, but its off-label use is a barrier to widespread acceptance. We found HU exposure is not significantly altered by liquid vs capsule formulation, and weight-based dosing schemes provide consistent exposure. HU is recommended for all children starting as young as 9 months of age with sickle cell anemia (SCA; HbSS and HbSβspan(0) thalassemia); however; a paucity of pediatric data exists regarding the pharmacokinetics (PK) or the exposure-response relationship of HU. This trial aimed to characterize the PK of HU in children and to evaluate and compare the bioavailability of a liquid vs capsule formulation. This multicenter; prospective; open-label trial enrolled 39 children with SCA who provided 682 plasma samples for PK analysis following administration of HU. Noncompartmental and population PK models are described. We report that liquid and capsule formulations of HU are bioequivalent; weight-based dosing schemes provide consistent drug exposure; and age-based dosing schemes are unnecessary. These data support the use of liquid HU in children unable to swallow capsules and in those whose weight precludes the use of fixed capsule formulations. Taken with existing safety and efficacy literature; these findings should encourage the use of HU across the spectrum of age and weight in children with SCA; and they should facilitate the expanded use of HU as recommended in the National Heart; Lung; and Blood Institute guidelines for individuals with SCA. © 2015, The American College of Clinical Pharmacology.

Design, synthesis and biological evaluation of phthalimide-alkylamine derivatives as balanced multifunctional cholinesterase and monoamine oxidase-B inhibitors for the treatment of Alzheimer's disease.

PubMed

Sang, Zhipei; Wang, Keren; Wang, Huifang; Yu, Lintao; Wang, Huijuan; Ma, Qianwen; Ye, Mengyao; Han, Xue; Liu, Wenmin

2017-11-15

A series of novel phthalimide-alkylamine derivatives were synthesized and evaluated as multi-functions inhibitors for the treatment of Alzheimer's disease (AD). The results showed that compound TM-9 could be regarded as a balanced multi-targets active molecule. It exhibited potent and balanced inhibitory activities against ChE and MAO-B (huAChE, huBuChE, and huMAO-B with IC 50 values of 1.2μM, 3.8μM and 2.6 μM, respectively) with low selectivity. Both kinetic analysis of AChE inhibition and molecular modeling study suggested that TM-9 binds simultaneously to the catalytic active site and peripheral anionic site of AChE. Interestingly, compound TM-9 abided by Lipinski's rule of five. Furthermore, our investigation proved that TM-9 indicated weak cytotoxicity, and it could cross the blood-brain barrier (BBB) in vitro. The results suggest that compound TM-9, an interesting multi-targeted active molecule, offers an attractive starting point for further lead optimization in the drug-discovery process against Alzheimer's disease. Copyright © 2017 Elsevier Ltd. All rights reserved.

PEG-rHuMGDF ameliorates thrombocytopenia in carboplatin-treated rats without inducing myelofibrosis.

PubMed

Ide, Y; Harada, K; Imai, A; Yanagida, M

1999-08-01

We examined the effects of pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF) on carboplatin-induced thrombocytopenia in rats. The focus was on whether myelofibrosis is associated with the PEG-rHuMGDF treatment in this chemotherapy model. After a single injection of carboplatin, rats received subcutaneous PEG-rHuMGDF at pharmacologic doses (1,3, or 30 micrograms/kg) or a vehicle daily for 7 days. PEG-rHuMGDF at more than 3 micrograms/kg ameliorated the thrombocytopenia at day 10. Histologically, no myelofibrosis was detected in the rats treated with PEG-rHuMGDF or vehicle. Subsequently, PEG-rHuMGDF at a suprapharmacologic dose (100 micrograms/kg) was subcutaneously administered to normal and to carboplatin-treated rats daily for 7 days. Histological analysis revealed that the treatment with PEG-rHuMGDF induced myelofibrosis in the normal rats but not in the carboplatin-treated rats. Additionally, the transforming growth factor-beta 1 (TGF-beta 1) levels in the extracellular fluid and the whole extract of the bone marrow were increased to a much lesser degree in the carboplatin-treated rats compared to the normal rats. These findings suggest that PEG-rHuMGDF is effective for carboplatin-induced thrombocytopenia. Proper control of platelet counts and TGF-beta 1 levels is essential so that myelofibrosis is not induced in clinical use.

Icariin combined with human umbilical cord mesenchymal stem cells significantly improve the impaired kidney function in chronic renal failure.

PubMed

Li, Wen; Wang, Li; Chu, Xiaoqian; Cui, Huantian; Bian, Yuhong

2017-04-01

At present, the main therapy for chronic renal failure (CRF) is dialysis and renal transplantation, but neither obtains satisfactory results. Human umbilical cord mesenchymal stem cells (huMSCs) are isolated from the fetal umbilical cord which has a high self-renewal and multi-directional differentiation potential. Icariin (ICA), a kidney-tonifying Chinese Medicine can enhance the multipotency of huMSCs. Therefore, this work seeks to employ the use of ICA-treated huMSCs for the treatment of chronic renal failure. Blood urea nitrogen and creatinine (Cr) analyses showed amelioration of functional parameters in ICA-treated huMSCs for the treatment of CRF rats at 3, 7, and 14 days after transplantation. ICA-treated huMSCs can obviously increase the number of cells in injured renal tissues at 3, 7, and 14 days after transplantation by optical molecular imaging system. Hematoxylin-eosin staining demonstrated that ICA-treated huMSCs reduced the levels of fibrosis in CRF rats at 14 days after transplantation. Superoxide dismutase and Malondialdehyde analyses showed that ICA-treated huMSCs reduced the oxidative damage in CRF rats. Moreover, transplantation with ICA-treated huMSCs decreased inflammatory responses, promoted the expression of growth factors, and protected injured renal tissues. Taken together, our findings suggest that ICA-treated huMSCs could improve the kidney function in CRF rats.

Simultaneous Administration of ADSCs-Based Therapy and Gene Therapy Using Ad-huPA Reduces Experimental Liver Fibrosis.

PubMed

Meza-Ríos, Alejandra; García-Benavides, Leonel; García-Bañuelos, Jesus; Salazar-Montes, Adriana; Armendáriz-Borunda, Juan; Sandoval-Rodríguez, Ana

2016-01-01

hADSCs transplantation in cirrhosis models improves liver function and reduces fibrosis. In addition, Ad-huPA gene therapy diminished fibrosis and increased hepatocyte regeneration. In this study, we evaluate the combination of these therapies in an advanced liver fibrosis experimental model. hADSCs were expanded and characterized before transplantation. Ad-huPA was simultaneously administrated via the ileac vein. Animals were immunosuppressed by CsA 24 h before treatment and until sacrifice at 10 days post-treatment. huPA liver expression and hADSCs biodistribution were evaluated, as well as the percentage of fibrotic tissue, hepatic mRNA levels of Col-αI, TGF-β1, CTGF, α-SMA, PAI-I, MMP2 and serum levels of ALT, AST and albumin. hADSCs homed mainly in liver, whereas huPA expression was similar in Ad-huPA and hADSCs/Ad-huPA groups. hADSCs, Ad-huPA and hADSCs/Ad-huPA treatment improves albumin levels, reduces liver fibrosis and diminishes Collagen α1, CTGF and α-SMA mRNA liver levels. ALT and AST serum levels showed a significant decrease exclusively in the hADSCs group. These results showed that combinatorial effect of cell and gene-therapy does not improve the antifibrogenic effects of individual treatments, whereas hADSCs transplantation seems to reduce liver fibrosis in a greater proportion.

Flexible DNA bending in HU–DNA cocrystal structures

PubMed Central

Swinger, Kerren K.; Lemberg, Kathryn M.; Zhang, Ying; Rice, Phoebe A.

2003-01-01

HU and IHF are members of a family of prokaryotic proteins that interact with the DNA minor groove in a sequence-specific (IHF) or non-specific (HU) manner to induce and/or stabilize DNA bending. HU plays architectural roles in replication initiation, transcription regulation and site-specific recombination, and is associated with bacterial nucleoids. Cocrystal structures of Anabaena HU bound to DNA (1P71, 1P78, 1P51) reveal that while underlying proline intercalation and asymmetric charge neutralization mechanisms of DNA bending are similar for IHF and HU, HU stabilizes different DNA bend angles (∼105–140°). The two bend angles within a single HU complex are not coplanar, and the resulting dihedral angle is consistent with negative supercoiling. Comparison of HU–DNA and IHF–DNA structures suggests that sharper bending is correlated with longer DNA binding sites and smaller dihedral angles. An HU-induced bend may be better modeled as a hinge, not a rigid bend. The ability to induce or stabilize varying bend angles is consistent with HU’s role as an architectural cofactor in many different systems that may require differing geometries. PMID:12853489

Optimization of the scan protocols for CT-based material extraction in small animal PET/CT studies

NASA Astrophysics Data System (ADS)

Yang, Ching-Ching; Yu, Jhih-An; Yang, Bang-Hung; Wu, Tung-Hsin

2013-12-01

We investigated the effects of scan protocols on CT-based material extraction to minimize radiation dose while maintaining sufficient image information in small animal studies. The phantom simulation experiments were performed with the high dose (HD), medium dose (MD) and low dose (LD) protocols at 50, 70 and 80 kVp with varying mA s. The reconstructed CT images were segmented based on Hounsfield unit (HU)-physical density (ρ) calibration curves and the dual-energy CT-based (DECT) method. Compared to the (HU;ρ) method performed on CT images acquired with the 80 kVp HD protocol, a 2-fold improvement in segmentation accuracy and a 7.5-fold reduction in radiation dose were observed when the DECT method was performed on CT images acquired with the 50/80 kVp LD protocol, showing the possibility to reduce radiation dose while achieving high segmentation accuracy.

Technical Note: Improving proton stopping power ratio determination for a deformable silicone-based 3D dosimeter using dual energy CT

DOE Office of Scientific and Technical Information (OSTI.GOV)

Taasti, Vicki Trier, E-mail: victaa@rm.dk; Høye, Ellen Marie; Hansen, David Christoffer

Purpose: The aim of this study was to investigate whether the stopping power ratio (SPR) of a deformable, silicone-based 3D dosimeter could be determined more accurately using dual energy (DE) CT compared to using conventional methods based on single energy (SE) CT. The use of SECT combined with the stoichiometric calibration method was therefore compared to DECT-based determination. Methods: The SPR of the dosimeter was estimated based on its Hounsfield units (HUs) in both a SECT image and a DECT image set. The stoichiometric calibration method was used for converting the HU in the SECT image to a SPR valuemore » for the dosimeter while two published SPR calibration methods for dual energy were applied on the DECT images. Finally, the SPR of the dosimeter was measured in a 60 MeV proton by quantifying the range difference with and without the dosimeter in the beam path. Results: The SPR determined from SECT and the stoichiometric method was 1.10, compared to 1.01 with both DECT calibration methods. The measured SPR for the dosimeter material was 0.97. Conclusions: The SPR of the dosimeter was overestimated by 13% using the stoichiometric method and by 3% when using DECT. If the stoichiometric method should be applied for the dosimeter, the HU of the dosimeter must be manually changed in the treatment planning system in order to give a correct SPR estimate. Using a wrong SPR value will cause differences between the calculated and the delivered treatment plans.« less

Single low-dose rHuIL-12 safely triggers multilineage hematopoietic and immune-mediated effects

PubMed Central

2014-01-01

Background Recombinant human interleukin 12 (rHuIL-12) regulates hematopoiesis and cell-mediated immunity. Based on these hematopoietic and immunomodulatory activities, a recombinant human IL-12 (rHuIL-12) is now under development to address the unmet need for a medical countermeasure against the hematopoietic syndrome of the acute radiation syndrome (HSARS) that occurs in individuals exposed to lethal radiation, and also to serve as adjuvant therapy that could provide dual hematopoietic and immunotherapeutic benefits in patients with cancer receiving chemotherapy. We sought to demonstrate in healthy subjects the safety of rHuIL-12 at single, low doses that are appropriate for use as a medical countermeasure for humans exposed to lethal radiation and as an immunomodulatory anti-cancer agent. Methods Two placebo-controlled, double-blinded studies assessed the safety, tolerability, pharmacokinetics and pharmacodynamics of rHuIL-12. The first-in-human (FIH) dose-escalation study randomized subjects to single subcutaneous injections of placebo or rHuIL-12 at 2, 5, 10, and 20 μg doses. Due to toxicity, dose was reduced to 15 μg and then to 12 μg. The phase 1b expansion study randomized subjects to the highest safe and well tolerated dose of 12 μg. Results Thirty-two subjects were enrolled in the FIH study: 4 active and 2 placebo at rHuIL-12 doses of 2, 5, 10, 12, and 15 μg; 1 active and 1 placebo at 20 μg. Sixty subjects were enrolled in the expansion study: 48 active and 12 placebo at 12 μg dose of rHuIL-12. In both studies, the most common adverse events (AEs) related to rHuIL-12 were headache, dizziness, and chills. No immunogenicity was observed. Elimination of rHuIL-12 was biphasic, suggesting significant distribution into extravascular spaces. rHuIL-12 triggered transient changes in neutrophils, platelets, reticulocytes, lymphocytes, natural killer cells, and CD34+ hematopoietic progenitor cells, and induced increases in interferon-γ and C-X-C motif chemokine 10. Conclusion A single low dose of rHuIl-12 administered subcutaneously can elicit hematological and immune-mediated effects without undue toxicity. The safety and the potent multilineage hematopoietic/immunologic effects triggered by low-dose rHuIL-12 support the development of rHuIL-12 both as a radiation medical countermeasure and as adjuvant immunotherapy for cancer. Trial registration ClinicalTrials.gov: NCT01742221 PMID:24725395

Stimulating angiogenesis mitigates the unloading-induced reduction in osteogenesis in early-stage bone repair in rats

PubMed Central

Matsumoto, Takeshi; Sato, Shota

2015-01-01

Accelerating fracture healing during bed rest allows early mobilization and avoids prolonged fracture healing times. We tested the hypothesis that stimulating angiogenesis with deferoxamine (DFO) mitigates the unloading-induced reduction in early-stage bone repair. Rats aged 12 weeks were subjected to cortical drilling on their tibial diaphysis under anesthesia and treated with hindlimb unloading (HU), HU and DFO administration (DFOHU), or weight bearing (WB) for 5 or 10 days (HU5/10, DFOHU5/10, WB5/10; n = 8 per groups) until sacrifice for vascular casting with a zirconium dioxide-based contrast agent. Taking advantage of its absorption discontinuity at the K-absorption edge, vascular and bone images in the drill-hole defects were acquired by synchrotron radiation subtraction CT. Bone repair was reduced in HU rats. The bone volume fraction (B.Vf) was 88% smaller in HU5 and 42% smaller in HU10 than in WB5/10. The bone segment densities (B.Seg) were 97% smaller in HU5 and 141% larger in HU10 than in WB5/10, and bone thickness (B.Th) was 38% smaller in HU10 than in WB10. The vascular volume fraction (V.Vf) was 35% and the mean vessel diameter (V.D) was 13% smaller in HU10 than in WB10. When compared according to categorized vessel sizes, V.Vf in the diameter ranges 20–30, 30–40, and >40 μm were smaller in HU10 than in WB10, and V.Seg in the diameter range >40 μm was smaller in HU10 than in WB10. In contrast, there was no difference in B.Vf between DFOHU5/10 and WB5/10 and in V.Vf between DFOHU10 and WB10, though B.Seg remained 86% smaller in DFOHU5 and 94% larger in DFOHU10 than in WB5/10, and B.Th and V.D were 23% and 14% lower in DFOHU10 than in WB10. Vessel size-specific V.Vf in the diameter ranges 10–20 and 20–30 μm was larger in DFOHU5 than in HU5. In conclusion, the enhanced angiogenic ingrowth mitigates the reduction in bone repair during mechanical unloading. PMID:25780087

The inhibition, reactivation and mechanism of VX-, sarin-, fluoro-VX and fluoro-sarin surrogates following their interaction with HuAChE and HuBuChE.

PubMed

Chao, Chih-Kai; Balasubramanian, Narayanaganesh; Gerdes, John M; Thompson, Charles M

2018-06-16

In this study, the mechanisms of HuAChE and HuBChE inhibition by Me-P(O) (OPNP) (OR) [PNP = p-nitrophenyl; R = CH 2 CH 3 , CH 2 CH 2 F, OCH(CH 3 ) 2 , OCH(CH 3 ) (CH 2 F)] representing surrogates and fluoro-surrogates of VX and sarin were studied by in vitro kinetics and mass spectrometry. The in vitro measures showed that the VX- and fluoro-VX surrogates were relatively strong inhibitors of HuAChE and HuBChE (k i  ∼ 10 5 -10 6  M -1 min -1 ) and underwent spontaneous and 2-PAM-mediated reactivation within 30 min. The sarin surrogates were weaker inhibitors of HuAChE and HuBChE (k i  ∼ 10 4 -10 5  M -1 min -1 ), and in general did not undergo spontaneous reactivation, although HuAChE adducts were partially reactivatable at 18 h using 2-PAM. The mechanism of HuAChE and HuBChE inhibition by the surrogates was determined by Q-TOF and MALDI-TOF mass spectral analyses. The surrogate-adducted proteins were trypsin digested and the active site-containing peptide bearing the OP-modified serine identified by Q-TOF as triply- and quadruply-charged ions representing the respective increase in mass of the attached OP moiety. Correspondingly, monoisotopic ions of the tryptic peptides representing the mass increase of the OP-adducted peptide was identified by MALDI-TOF. The mass spectrometry analyses validated the identity of the OP moiety attached to HuAChE or HuBChE as MeP(O) (OR)-O-serine peptides (loss of the PNP leaving group) via mechanisms consistent with those found with chemical warfare agents. MALDI-TOF MS analyses of the VX-modified peptides versus time showed a steady reduction in adduct versus parent peptide (reactivation), whereas the sarin-surrogate-modified peptides remained largely intact over the course of the experiment (24 h). Overall, the presence of a fluorine atom on the surrogate modestly altered the rate constants of inhibition and reactivation, however, the mechanism of inhibition (ejection of PNP group) did not change. Copyright © 2018. Published by Elsevier B.V.

Estrous Cyclicity in Mice During Simulated Weightlessness

NASA Technical Reports Server (NTRS)

Moyer, E. L.; Talyansky, Y.; Scott, R. T.; Tash, J. S.; Christenson, L. K.; Alwood, J. S.; Ronca, A. E.

2017-01-01

Hindlimb unloading (HU) is a rodent model system used to simulate weightlessness experienced in space. However, some effects of this approach on rodent physiology are under-studied, specifically the effects on ovarian estrogen production which drives the estrous cycle. To resolve this deficiency, we conducted a ground-based validation study using the HU model, while monitoring estrous cycles in 16-weeks-old female C57BL6 mice. Animals were exposed to HU for 12 days following a 3 day HU cage acclimation period, and estrous cycling was analyzed in HU animals (n=22), normally loaded HU Cage Pair-Fed controls (CPF; n=22), and Vivarium controls fed ad libitum (VIV; n=10). Pair feeding was used to control for potential nutritional deficits on ovarian function. Vaginal cells were sampled daily in all mice via saline lavage. Cells were dried and stained with crystal violet, and the smears evaluated using established vaginal cytology techniques by two individuals blinded to the animal treatment group. Estrous cyclicity was disrupted in nearly all HU and CPF mice, while those maintained in VIV had an average normal cycle length of 4.8+/- 0.5 days, with all stages in the cycle visibly observed. CPF and HU animals arrested in the diestrous phase, which precedes the pre-ovulatory estrogen surge. Additionally, infection-like symptoms characterized by vaginal discharge and swelling arose in several HU animals, which we suspect was due to an inability of these mice to properly groom themselves, and/or due to the change in the gravity vector relative to the vaginal opening, which prevented drainage of the lavage solution. Pair-feeding resulted in similar weight gains of HU and CPF (1.5% vs 3.0%, respectively). The current results indicate that pair-feeding controlled weight gain and that the HU cage alone influenced estrous cyclicity. Thus, longer acclimation needs to be tested to determine if and when normal estrous cycling resumes in non-loaded mice in HU cages prior to HU testing. Future studies might also examine whether modifications to the vaginal lavage procedure might prevent the onset of the infection-like symptoms, and allow estrous cyclicity to be measured in this model system. Research supported by NNX15AB48G to JST.

The Effects of Ligustrazine on the Ca2+ Concentration of Soleus and Gastrocnemius Muscle Fibers in Hindlimb Unloaded Rat

NASA Astrophysics Data System (ADS)

Gao, Yunfang; Goswami, Nandu; Du, Bei; Hu, Huanxin; Wu, Xue

Background Spaceflight or inactivity (bed rest, limb immobilization, hindlimb unloading) causes skeletal muscle atrophy. Recent studies show that an increase in protein degradation is an important mechanism for disuse atrophy. Furthermore, the calcium overload of disuse-atrophied muscle fiber has been shown to initiate the skeletal muscle proteolysis in disuse atrophy. Ligustrazine (tetramethylpyrazine, TMP), one of the important active ingredient extracted from Chuanxiong, has been shown by our group to increase muscle fiber cross-sectional area in atrophied soleus induced by 14 days hindlimb unloading. However, the underlying mechanisms of ligustrazine effects on disuse-atrophied muscle fibers remain unknown. Objective: We investigated the effects of ligustrazine on the cytoplasmic calcium overloading in soleus and gastrocnemius in 14 days hindlimb unloaded (HU) rats. Methods: Adult female Sprague-Dawley rats were matched for body mass and randomly assigned to three groups (n=8, each group): 1) synchronous control (CON); HU + intragastric water instillation (HU+W); HU + intragastric 60.0 mg kg-1 ligustrazine instillation (HU+Tmp). Laser scanning confocal microscope assessed the concentrations of cytoplasmic calcium ions. Spaceflight disuse atrophy was simulated by hindlimb unloading, provided by tail suspension. Results: 1) Compared with CON, the concentration of soleus intracellular calcium ion in HU+W and HU+Tmp increased 330% and 86% respectively P<0.01). Compared with HU+W, the concentration of soleus intracellular calcium ion in HU+Tmp decreased by 130% P<0.01). 2) Compared with CON, the concentration of gastrocnemius intracellular calcium ion in HU+W and HU+Tmp increased 189.8% and 32.1% respectively P<0.01). Compared with HU+W, the concentration of gastrocnemius intracellular calcium ion in HU+Tmp decreased by 119.3% (P<0.01). Conclusion: After 14 days of hindlimb unloading, cytoplasmic calcium of soleus (slow-twitch muscle) and gastrocnemius (fast-twitch muscle) showed significant overload. This was especially true for the soleus. Ligustrazine appears to inhibit the cytoplasmic calcium overload thus leadig to lesser muscle atrophy in hindlimb unloaded animals. Therefore, ligustrazine may play important role in preventing muscle loss during spaceflight. Key words: Ligustrazine; Tetramethylpyrazine; disuse atrophy; calcium overload; soleus; gastrocnemius; spaceflight This work was supported by funds from the National Natural Science Foundation of China (Grant No. 31270455), International Scientific and Technological Cooperation Projects in Shaanxi Province of China (Grant No. 2013KW26-01).

A new risk stratification algorithm for the management of patients with adrenal incidentalomas.

PubMed

Birsen, Onur; Akyuz, Muhammet; Dural, Cem; Aksoy, Erol; Aliyev, Shamil; Mitchell, Jamie; Siperstein, Allan; Berber, Eren

2014-10-01

Although adrenal incidentalomas (AI) are detected in ≤5% of patients undergoing chest and abdominal computed tomography (CT), their management is challenging. The current guidelines include recommendations from the National Institutes of Health, the American Association of Endocrine Surgeons (AAES), and the American Association for Cancer Education (AACE). The aim of this study was to develop a new risk stratification model and compare its performance against the existing guidelines for managing AI. A risk stratification model was designed by assigning points for adrenal size (1, 2, or 3 points for tumors <4, 4-6, or >6 cm, respectively) and Hounsfield unit (HU) density on noncontrast CT (1, 2, or 3 points for HU <10, 10-20, or >20, respectively). This model was applied retrospectively to 157 patients with AI managed in an endocrine surgery clinic to assign a score to each tumor. The utility of this model versus the AAES/AACE guidelines was assessed. Of the 157 patients, 54 (34%), had tumors <4 cm with HU <10 (a score of 2). One third of these were hormonally active on biochemical workup and underwent adrenalectomy. The remaining two thirds were nonsecretory lesions and have been followed conservatively with annual testing. In 103 patients (66%), the adrenal mass was >4 cm and/or had indeterminate features on noncontrast CT (HU >10, irregular borders, heterogeneity), and adrenalectomy was performed after hormonal evaluation was completed (10 were hormonally active on biochemical testing). Seven of these patients (7%) had adrenocortical cancer on final pathology with tumor size <4 cm in 0, 4-6 cm in 1, and >6 cm in 5 patients. Of the hormonally inactive patients, 32% had a score of 3, 38% 4, and 30% 5 or 6. The incidence of adrenocortical cancer in these subgroups was 0, 0, and 25%, respectively. This study shows that an algorithm that utilizes the hormonal activity at the first decision step followed by a consolidated risk stratification, based on tumor size and HU density, has a potential to spare a substantial number of patients from unnecessary "diagnostic" surgery for AI. Copyright © 2014 Elsevier Inc. All rights reserved.

WE-AB-202-05: Validation of Lung Stress Maps for CT-Ventilation Imaging

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cazoulat, G; Jolly, S; Matuszak, M

Purpose: To date, lung CT-ventilation imaging has been based on quantification of local breathing-induced changes in Hounsfield Units (HU) or volume. This work investigates the use of a stress map resulting from a biomechanical deformable image registration (DIR) algorithm as a metric of the ventilation function. Method: Eight lung cancer patients presenting different kinds of ventilation defects were retrospectively analyzed. Additionally, to the 4DCT acquired for radiotherapy planning, five of them had PET and three had SPECT imaging following inhalation of Ga-68 and Tc-99m, respectively. For each patient, the inhale phase of the 4DCT was registered to the exhale phasemore » using Morfeus, a biomechanical DIR algorithm based on the determination of boundary conditions on the lung surfaces and vessel tree. To take into account the heterogeneity of the tissue stiffness in the stress map estimation, each tetrahedral element of the finite-element model was assigned a Young’s modulus ranging from 60kPa to 12MPa, as a function of the HU in the inhale CT. The node displacements and element stresses resulting from the numerical simulation were used to generate three CT-ventilation maps based on: (i) volume changes (Jacobian determinant), (ii) changes in HU, (iii) the maximum principal stress. The voxel-wise correlation between each CT-ventilation map and the PET or SPECT V image was computed in a lung mask. Results: For patients with PET, the mean (min-max) Spearman correlation coefficients r were: 0.33 (0.19–0.45), 0.36 (0.16–0.51) and 0.42 (0.21–0.59) considering the Jacobian, changes in HU and maximum principal stress, respectively. For patients with SPECT V, the mean r were: 0.12 (−0.12–0.43), 0.29 (0.22–0.45) and 0.33 (0.25–0.39). Conclusion: The maximum principal stress maps showed a stronger correlation with the ventilation images than the previously proposed Jacobian or change in HU maps. This metric thus appears promising for CT-ventilation imaging. This work was funded in part by NIH P01CA059827.« less

Masking Misfit in Confirmatory Factor Analysis by Increasing Unique Variances: A Cautionary Note on the Usefulness of Cutoff Values of Fit Indices

ERIC Educational Resources Information Center

Heene, Moritz; Hilbert, Sven; Draxler, Clemens; Ziegler, Matthias; Buhner, Markus

2011-01-01

Fit indices are widely used in order to test the model fit for structural equation models. In a highly influential study, Hu and Bentler (1999) showed that certain cutoff values for these indices could be derived, which, over time, has led to the reification of these suggested thresholds as "golden rules" for establishing the fit or other aspects…

Efficacy of human serum butyrylcholinesterase against sarin vapor.

PubMed

Saxena, Ashima; Sun, Wei; Dabisch, Paul A; Hulet, Stanley W; Hastings, Nicholas B; Jakubowski, Edward M; Mioduszewski, Robert J; Doctor, Bhupendra P

2008-09-25

Human serum butyrylcholinesterase (Hu BChE) is currently under advanced development as a pretreatment drug for organophosphate (OP) poisoning in humans. It was shown to protect mice, rats, guinea pigs, and monkeys against multiple LD(50) challenges of OP nerve agents by i.v. or s.c. bolus injections. Since inhalation is the most likely route of exposure to OP nerve agents on the battlefield or in public places, the aim of this study was to evaluate the efficacy of Hu BChE against whole-body inhalation exposure to sarin (GB) vapor. Male Göttingen minipigs were subjected to one of the following treatments: (1) air exposure; (2) GB vapor exposure; (3) pretreatment with 3 mg/kg of Hu BChE followed by GB vapor exposure; (4) pretreatment with 6.5 mg/kg of Hu BChE followed by GB vapor exposure; (5) pretreatment with 7.5 mg/kg of Hu BChE followed by GB vapor exposure. Hu BChE was administered by i.m. injection, 24h prior to whole-body exposure to GB vapor at a concentration of 4.1 mg/m(3) for 60 min, a dose lethal to 99% of untreated exposed pigs (LCt99). EEG, ECG, and pupil size were monitored throughout exposure, and blood drawn from a surgically implanted jugular catheter before and throughout the exposure period, was analyzed for acetylcholinesterase (AChE) and BChE activities, and the amount of GB present in plasma. All animals exposed to GB vapor alone or pretreated with 3 or 6.5 mg/kg of Hu BChE, died following exposure to GB vapor. All five animals pretreated with 7.5 mg/kg of Hu BChE survived the GB exposure. The amount of GB bound in plasma was 200-fold higher compared to that from plasma of pigs that did not receive Hu BChE, suggesting that Hu BChE was effective in scavenging GB in blood. Additionally, pretreatment with 7.5 mg/kg of Hu BChE prevented cardiac abnormalities and seizure activity observed in untreated animals and those treated with lower doses of Hu BChE.

Recovery Optimization and Survival of the Human Norovirus Surrogates Feline Calicivirus and Murine Norovirus on Carpet.

PubMed

Buckley, David; Fraser, Angela; Huang, Guohui; Jiang, Xiuping

2017-11-15

Carpets have been implicated in prolonged and reoccurring outbreaks of human noroviruses (HuNoV), the leading cause of acute gastroenteritis worldwide. Viral recovery from environmental surfaces, such as carpet, remains undeveloped. Our aim was to determine survival of HuNoV surrogates on an understudied environmental surface, carpet. First, we measured the zeta potential and absorption capacity of wool and nylon carpet fibers, we then developed a minispin column elution (MSC) method, and lastly we characterized the survival of HuNoV surrogates, feline calicivirus (FCV) and murine norovirus (MNV), over 60 days under 30 and 70% relative humidity (RH) on two types of carpet and one glass surface. Carpet surface charge was negative between relevant pH values (i.e., pH 7 to 9). In addition, wool could absorb approximately two times more liquid than nylon. The percent recovery efficiency obtained by the MSC method ranged from 4.34 to 20.89% and from 30.71 to 54.14% for FCV and MNV on carpet fibers, respectively, after desiccation. Overall, elution buffer type did not significantly affect recovery. Infectious FCV or MNV survived between <1 and 15 or between 3 and 15 days, respectively. However, MNV survived longer under some conditions and at significantly ( P < 0.05) higher titers compared to FCV. Albeit, surrogates followed similar survival trends, i.e., both survived longest on wool then nylon and glass, while 30% RH provided a more hospitable environment compared to 70% RH. Reverse transcription-quantitative PCR signals for both surrogates were detectable for the entire study, but FCV genomic copies experienced significantly higher reductions (<3.80 log 10 copies) on all surfaces compared to MNV (<1.10 log 10 copies). IMPORTANCE Human noroviruses (HuNoV) are the leading cause of acute gastroenteritis worldwide. Classical symptoms of illness include vomiting and diarrhea which could lead to severe dehydration and death. HuNoV are transmitted by the fecal-oral or vomitus-oral route via person-to-person contact, food, water, and/or environmental surfaces. Published laboratory-controlled studies have documented the environmental stability of HuNoV on hard surfaces, but there is limited laboratory-based evidence available about survival on soft surfaces, e.g., carpet and upholstered furniture. Several epidemiological reports have suggested soft surfaces may be HuNoV fomites illustrating the importance of conducting a survival study. The three objectives of our research were to demonstrate techniques to characterize soft surfaces, develop a viral elution method for carpet, and characterize the survival of HuNoV surrogates on carpet. These results can be used to improve microbial risk assessments, the development of much-needed soft surface disinfectant, and standardizing protocols for future soft surface studies. Copyright © 2017 American Society for Microbiology.

Intensity-based dual model method for generation of synthetic CT images from standard T2-weighted MR images - Generalized technique for four different MR scanners.

PubMed

Koivula, Lauri; Kapanen, Mika; Seppälä, Tiina; Collan, Juhani; Dowling, Jason A; Greer, Peter B; Gustafsson, Christian; Gunnlaugsson, Adalsteinn; Olsson, Lars E; Wee, Leonard; Korhonen, Juha

2017-12-01

Recent studies have shown that it is possible to conduct entire radiotherapy treatment planning (RTP) workflow using only MR images. This study aims to develop a generalized intensity-based method to generate synthetic CT (sCT) images from standard T2-weighted (T2 w ) MR images of the pelvis. This study developed a generalized dual model HU conversion method to convert standard T2 w MR image intensity values to synthetic HU values, separately inside and outside of atlas-segmented bone volume contour. The method was developed and evaluated with 20 and 35 prostate cancer patients, respectively. MR images with scanning sequences in clinical use were acquired with four different MR scanners of three vendors. For the generated synthetic CT (sCT) images of the 35 prostate patients, the mean (and maximal) HU differences in soft and bony tissue volumes were 16 ± 6 HUs (34 HUs) and -46 ± 56 HUs (181 HUs), respectively, against the true CT images. The average of the PTV mean dose difference in sCTs compared to those in true CTs was -0.6 ± 0.4% (-1.3%). The study provides a generalized method for sCT creation from standard T2 w images of the pelvis. The method produced clinically acceptable dose calculation results for all the included scanners and MR sequences. Copyright © 2017 Elsevier B.V. All rights reserved.

Pleiotropic activity of systemically delivered angiogenin in the SOD1G93A mouse model.

PubMed

Crivello, Martin; O'Riordan, Saidhbhe L; Woods, Ina; Cannon, Sarah; Halang, Luise; Coughlan, Karen S; Hogg, Marion C; Lewandowski, Sebastian A; Prehn, Jochen H M

2018-05-01

Loss-of-function mutations in the angiogenin (ANG) gene have been identified in familial and sporadic ALS patients. Previous work from our group identified human ANG (huANG) to protect motoneurons in vitro, and provided proof-of-concept that daily intraperitoneal (i.p.) huANG injections post-symptom onset increased lifespan and delayed disease progression in SOD1 G93A mice. huANG's mechanism of action remains less well understood. Here, we implemented a preclinical in vivo design to validate our previous results, provide pharmacokinetic and protein distribution data after systemic administration, and explore potential pleiotropic activities of huANG in vivo. SOD1 G93A mice (n = 45) and non-transgenic controls (n = 31) were sex- age- and litter-matched according to the 2010 European ALS/MND group guidelines, and treated with huANG (1 μg, i.p., 3 times/week) or vehicle from 90 days on. huANG treatment increased survival and delayed motor dysfunction as assessed by rotarod in SOD1 G93A mice. Increased huANG serum levels were detectable 2 and 24 h after i.p. injection equally in transgenic and non-transgenic mice. Exogenous huANG localized to spinal cord astrocytes, supporting a glia-mediated, paracrine mechanism of action; uptake into endothelial cells was also observed. 1 μg huANG or vehicle were administered from 90 to 115 days of age for histological analysis. Vehicle-treated SOD1 G93A mice showed decreased motoneuron numbers and vascular length per ventral horn area, while huANG treatment resulted in improved vascular network maintenance and motoneuron survival. Our data suggest huANG represents a new class of pleiotropic ALS therapeutic that acts on the spinal cord vasculature and glia to delay motoneuron degeneration and disease progression. Copyright © 2018 Elsevier Ltd. All rights reserved.

Transgenic chickens expressing human urokinase-type plasminogen activator.

PubMed

Lee, Sung Ho; Gupta, Mukesh Kumar; Ho, Young Tae; Kim, Teoan; Lee, Hoon Taek

2013-09-01

Urokinase-type plasminogen activator is a serine protease that is clinically used in humans for the treatment of thrombolytic disorders and vascular diseases such as acute ischemic stroke and acute peripheral arterial occlusion. This study explored the feasibility of using chickens as a bioreactor for producing human urokinase-type plasminogen activator (huPA). Recombinant huPA gene, under the control of a ubiquitous Rous sarcoma virus promoter, was injected into the subgerminal cavity of freshly laid chicken eggs at stage X using the replication-defective Moloney murine leukemia virus (MoMLV)-based retrovirus vectors encapsidated with VSV-G (vesicular stomatitis virus G) glycoprotein. A total of 38 chicks, out of 573 virus-injected eggs, hatched and contained the huPA gene in their various body parts. The mRNA transcript of the huPA gene was present in various organs, including blood and egg, and was germ-line transmitted to the next generation. The level of active huPA protein was 16-fold higher in the blood of the transgenic chicken than in the nontransgenic chicken (P < 0.05). The expression of huPA protein in eggs increased from 7.82 IU/egg in the G0 generation to 17.02 IU/egg in the G1 generation. However, huPA-expressing embryos had reduced survival and hatchability at d 18 and 21 of incubation, respectively, and the blood clotting time was significantly higher in transgenic chickens than their nontransgenic counterparts (P < 0.05). Furthermore, adult transgenic rooster showed reduced (P < 0.05) fertility, as revealed by reduced volume of semen ejaculate, sperm concentration, and sperm viability. Taken together, our data suggest that huPA transgenic chickens could be successfully produced by the retroviral vector system. Transgenic chickens, expressing the huPA under the control of a ubiquitous promoter, may not only be used as a bioreactor for pharming of the huPA drug but also be useful for studying huPA-induced bleeding and other disorders.

SU-E-J-267: Change in Mean CT Intensity of Lung Tumors During Radiation Treatment

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mahon, R; Tennyson, N; Weiss, E

2015-06-15

Purpose: To evaluate CT intensity change of lung tumors during radiation therapy. Methods: Repeated 4D CT images were acquired on a CT simulator during the course of therapy for 27 lung cancer patients on IRB approved protocols. All subjects received definitive radiation treatment ± chemotherapy. CT scans were completed prior to treatment, and 2–7 times during the treatment course. Primary tumor was delineated by an experienced Radiation Oncologist. Contours were thresholded between −100 HU and 200 HU to remove airways and bone. Correlations between the change in the mean tumor intensity and initial tumor intensity, SUVmax, and tumor volume changemore » rate were investigated. Reproducibility was assessed by evaluating the variation in mean intensity over all phases in 4DCT, for a subgroup of 19 subjects. Results: Reproducibility of tumor intensity between phases as characterized by the root mean square of standard deviation across 19 subjects was 1.8 HU. Subjects had a mean initial tumor intensity of 16.5 ± 11.6 HU and an overall reduction in HU by 10.3 ± 8.5 HU. Evaluation of the changes in tumor intensity during treatment showed a decrease of 0.3 ± 0.3 HU/day for all subjects, except three. No significant correlation was found between change in HU/day and initial HU intensity (p=0.53), initial PET SUVmax (p=0.69), or initial tumor volume (p=0.70). The rate of tumor volume change was weakly correlated (R{sup 2}=0.05) with HU change (p=0.01). Conclusion: Most lung cancer subjects showed a marked trend of decreasing mean tumor CT intensity throughout radiotherapy, including early in the treatment course. Change in HU/day is not correlated with other potential early predictors for response, such as SUV and tumor volume change. This Result supports future studies to evaluate change in tumor intensity on CT as an early predictor of response.« less

Technical Note: Evaluation of a 160-mm/256-row CT scanner for whole-heart quantitative myocardial perfusion imaging.

PubMed

So, Aaron; Imai, Yasuhiro; Nett, Brian; Jackson, John; Nett, Liz; Hsieh, Jiang; Wisenberg, Gerald; Teefy, Patrick; Yadegari, Andrew; Islam, Ali; Lee, Ting-Yim

2016-08-01

The authors investigated the performance of a recently introduced 160-mm/256-row CT system for low dose quantitative myocardial perfusion (MP) imaging of the whole heart. This platform is equipped with a gantry capable of rotating at 280 ms per full cycle, a second generation of adaptive statistical iterative reconstruction (ASiR-V) to correct for image noise arising from low tube voltage potential/tube current dynamic scanning, and image reconstruction algorithms to tackle beam-hardening, cone-beam, and partial-scan effects. Phantom studies were performed to investigate the effectiveness of image noise and artifact reduction with a GE Healthcare Revolution CT system for three acquisition protocols used in quantitative CT MP imaging: 100, 120, and 140 kVp/25 mAs. The heart chambers of an anthropomorphic chest phantom were filled with iodinated contrast solution at different concentrations (contrast levels) to simulate the circulation of contrast through the heart in quantitative CT MP imaging. To evaluate beam-hardening correction, the phantom was scanned at each contrast level to measure the changes in CT number (in Hounsfield unit or HU) in the water-filled region surrounding the heart chambers with respect to baseline. To evaluate cone-beam artifact correction, differences in mean water HU between the central and peripheral slices were compared. Partial-scan artifact correction was evaluated from the fluctuation of mean water HU in successive partial scans. To evaluate image noise reduction, a small hollow region adjacent to the heart chambers was filled with diluted contrast, and contrast-to-noise ratio in the region before and after noise correction with ASiR-V was compared. The quality of MP maps acquired with the CT system was also evaluated in porcine CT MP studies. Myocardial infarct was induced in a farm pig from a transient occlusion of the distal left anterior descending (LAD) artery with a catheter-based interventional procedure. MP maps were generated from the dynamic contrast-enhanced (DCE) heart images taken at baseline and three weeks after the ischemic insult. Their results showed that the phantom and animal images acquired with the CT platform were minimally affected by image noise and artifacts. For the beam-hardening phantom study, changes in water HU in the wall surrounding the heart chambers greatly reduced from >±30 to ≤ ± 5 HU at all kVp settings except one region at 100 kVp (7 HU). For the cone-beam phantom study, differences in mean water HU from the central slice were less than 5 HU at two peripheral slices with each 4 cm away from the central slice. These findings were reproducible in the pig DCE images at two peripheral slices that were 6 cm away from the central slice. For the partial-scan phantom study, standard deviations of the mean water HU in 10 successive partial scans were less than 5 HU at the central slice. Similar observations were made in the pig DCE images at two peripheral slices with each 6 cm away from the central slice. For the image noise phantom study, CNRs in the ASiR-V images were statistically higher (p < 0.05) than the non-ASiR-V images at all kVp settings. MP maps generated from the porcine DCE images were in excellent quality, with the ischemia in the LAD territory clearly seen in the three orthogonal views. The study demonstrates that this CT system can provide accurate and reproducible CT numbers during cardiac gated acquisitions across a wide axial field of view. This CT number fidelity will enable this imaging tool to assess contrast enhancement, potentially providing valuable added information beyond anatomic evaluation of coronary stenoses. Furthermore, their results collectively suggested that the 100 kVp/25 mAs protocol run on this CT system provides sufficient image accuracy at a low radiation dose (<3 mSv) for whole-heart quantitative CT MP imaging.

Effects of Hindlimb Unweighting on MBP and GDNF Expression and Morphology in Rat Dorsal Root Ganglia Neurons.

PubMed

Zhang, Heng; Ren, Ning-Tao; Zhou, Fang-Qiang; Li, Jie; Lei, Wei; Liu, Ning; Bi, Long; Wu, Zi-Xiang; Zhang, Ran; Zhang, Yong-Gang; Cui, Geng

2016-09-01

With the development of technology and space exploration, studies on long-duration space flights have shown that microgravity induces damage to multiple organs, including the dorsal root ganglia (DRG). However, very little is known about the effects of long-term microgravity on DRG neurons. This study investigated the effects of microgravity on lumbar 5 (L5) DRG neurons in rats using the hindlimb unweighting (HU) model. Male (M) and female (F) Sprague-Dawley rats were randomly divided into M- and F-control (CON) groups and M- and F-HU groups, respectively (n = 10). At the end of HU treatment for 4 weeks, morphological changes were detected. Myelin basic protein (MBP) and degenerated myelin basic protein (dgen-MBP) expressions were analyzed by immunofluorescence and western blot assays. Glial cell line-derived neurotrophic factor (GDNF) protein and mRNA expressions were also analyzed by immunohistochemistry, western blot, and RT-PCR analysis, respectively. Compared with the corresponding CON groups, the HU groups exhibited slightly loose junctions between DRG neurons, some separated ganglion cells and satellite cells, and lightly stained Nissl bodies that were of smaller size and had a scattered distribution. High levels of dgen-MBP and low MBP expressions were appeared and GDNF expressions were significantly decreased in both HU groups. Changes were more pronounced in the F-HU group than in the M-HU group. In conclusion, HU treatment induced damage of L5 DRG neurons, which was correlated with decreased total MBP protein expression, increased dgen-MBP expression, and reduced GDNF protein and mRNA expression. Importantly, these changes were more severe in F-HU rats compared with M-HU rats.

Altered regulation of ELAVL1/HuR in HLA-B27-expressing U937 monocytic cells.

PubMed

Sahlberg, Anna S; Ruuska, Marja; Granfors, Kaisa; Penttinen, Markus A

2013-01-01

To investigate the role of HLA-B27 expression in the regulation of RNA binding protein (RBP) Embryonic Lethal Abnormal Vision (ELAV) L1/Human antigen R (HuR) expression in Salmonella-infected or LPS-stimulated human monocytic cells, since HuR is a critical regulator of the post-transcriptional fate of many genes (e.g. TNFα) important in inflammatory response. U937 monocytic cells were stably transfected with pSV2neo resistant vector (mock), wild type HLA-B27, or mutated HLA-B27 with amino acid substitutions in the B pocket. Cells were differentiated, infected with Salmonella enteritidis or stimulated with lipopolysaccharide. The expression levels of HuR protein and cleavage products (CP1 and CP2) were detected by Western blotting and flow cytometry. Specific inhibitors were used to study the role of PKR and p38 in HuR expression and generation of CPs. TNFα and IL-10 secretion after p38 and PKR inhibition were measured by ELISA. Full length HuR is overexpressed and HuR cleavage is disturbed in U937 monocytic cells expressing HLA-B27 heavy chains (HC). Increased full length HuR expression, disturbed cleavage and reduced dependence on PKR after infection correlate with the expression of glutamic acid 45 in the B pocket that is linked to the misfolding of HLA-B27. Results show that the expression of HLA-B27 HCs modulates the intracellular environment of U937 monocyte/macrophages by altering HuR regulation. This phenomenon is at least partly dependent on the misfolding feature of the B27 molecule. Since HuR is an important regulator of multiple genes involved in inflammatory response observations offer an explanation how HLA-B27 may modulate inflammatory response.

Randomized feasibility trial to improve hydroxyurea adherence in youth ages 10-18 years through community health workers: The HABIT study.

PubMed

Green, Nancy S; Manwani, Deepa; Matos, Sergio; Hicks, April; Soto, Luisa; Castillo, Yina; Ireland, Karen; Stennett, Yvonne; Findley, Sally; Jia, Haomiao; Smaldone, Arlene

2017-12-01

The main therapeutic intervention for sickle cell disease (SCD) is hydroxyurea (HU). The effect of HU is largely through dose-dependent induction of fetal hemoglobin (HbF). Poor HU adherence is common among adolescents. Our 6-month, two-site pilot intervention trial, "HABIT," was led by culturally aligned community health workers (CHWs). CHWs performed support primarily through home visits, augmented by tailored text message reminders. Dyads of youth with SCD ages 10-18 years and a parent were enrolled. A customized HbF biomarker, the percentage decrease from each patients' highest historical HU-induced HbF, "Personal best," was used to qualify for enrollment and assess HU adherence. Two primary outcomes were as follows: (1) intervention feasibility and acceptability and (2) HU adherence measured in three ways: monthly percentage improvement toward HbF Personal best, proportion of days covered (PDC) by HU, and self-report. Twenty-eight dyads were enrolled, of which 89% were retained. Feasibility and acceptability were excellent. Controlling for group assignment and month of intervention, the intervention group improved percentage decrease from Personal best by 2.3% per month during months 0-4 (P = 0.30), with similar improvement in adherence demonstrated using pharmacy records. Self-reported adherence did not correlate. Dyads viewed CHWs as supportive for learning about SCD and HU, living with SCD and making progress in coordinated self-management responsibility to support a daily HU habit. Most parents and youth appreciated text message HU reminders. The HABIT pilot intervention demonstrated feasibility and acceptability with promising effect toward improved medication adherence. Testing in a larger multisite intervention trial is warranted. © 2017 Wiley Periodicals, Inc.

Simultaneous Administration of ADSCs-Based Therapy and Gene Therapy Using Ad-huPA Reduces Experimental Liver Fibrosis

PubMed Central

Meza-Ríos, Alejandra; García-Benavides, Leonel; García-Bañuelos, Jesus; Salazar-Montes, Adriana; Armendáriz-Borunda, Juan; Sandoval-Rodríguez, Ana

2016-01-01

Background and Aims hADSCs transplantation in cirrhosis models improves liver function and reduces fibrosis. In addition, Ad-huPA gene therapy diminished fibrosis and increased hepatocyte regeneration. In this study, we evaluate the combination of these therapies in an advanced liver fibrosis experimental model. Methods hADSCs were expanded and characterized before transplantation. Ad-huPA was simultaneously administrated via the ileac vein. Animals were immunosuppressed by CsA 24 h before treatment and until sacrifice at 10 days post-treatment. huPA liver expression and hADSCs biodistribution were evaluated, as well as the percentage of fibrotic tissue, hepatic mRNA levels of Col-αI, TGF-β1, CTGF, α-SMA, PAI-I, MMP2 and serum levels of ALT, AST and albumin. Results hADSCs homed mainly in liver, whereas huPA expression was similar in Ad-huPA and hADSCs/Ad-huPA groups. hADSCs, Ad-huPA and hADSCs/Ad-huPA treatment improves albumin levels, reduces liver fibrosis and diminishes Collagen α1, CTGF and α-SMA mRNA liver levels. ALT and AST serum levels showed a significant decrease exclusively in the hADSCs group. Conclusions These results showed that combinatorial effect of cell and gene-therapy does not improve the antifibrogenic effects of individual treatments, whereas hADSCs transplantation seems to reduce liver fibrosis in a greater proportion. PMID:27992438

Hepatitis C virus core protein potentiates proangiogenic activity of hepatocellular carcinoma cells.

PubMed

Shao, Yu-Yun; Hsieh, Min-Shu; Wang, Han-Yu; Li, Yong-Shi; Lin, Hang; Hsu, Hung-Wei; Huang, Chung-Yi; Hsu, Chih-Hung; Cheng, Ann-Lii

2017-10-17

Increased angiogenic activity has been demonstrated in hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC), but the mechanism was unclear. To study the role of HCV core protein, we used tube formation and Matrigel plug assays to assess the proangiogenic activity of an HCC cell line, HuH7, and 2 of its stable clones-HuH7-core-high and HuH7-core-low, with high and low HCV core protein expression, respectively. In both assays, HuH7-core-high and HuH7-core-low cells dose-dependently induced stronger angiogenesis than control cells. HuH7 cells with HCV core protein expression showed increased mRNA and protein expression of vascular endothelial growth factor (VEGF). VEGF inhibition by bevacizumab reduced the proangiogenic activity of HuH7-core-high cells. The promotor region of VEGF contains the binding site of activator protein-1 (AP-1). Compared with controls, HuH7-core-high cells had an increased AP-1 activity and nuclear localization of phospho-c-jun. AP-1 inhibition using either RNA knockdown or AP-1 inhibitors reduced the VEGF mRNA expression and the proangiogenic activity of HuH7-core-high cells. Among 131 tissue samples from HCC patients, HCV-related HCC revealed stronger VEGF expression than did hepatitis B virus-related HCC. In conclusion, increased VEGF expression through AP-1 activation is a crucial mechanism underlying the proangiogenic activity of the HCV core protein in HCC cells.

Hepatitis C virus core protein potentiates proangiogenic activity of hepatocellular carcinoma cells

PubMed Central

Shao, Yu-Yun; Hsieh, Min-Shu; Wang, Han-Yu; Li, Yong-Shi; Lin, Hang; Hsu, Hung-Wei; Huang, Chung-Yi; Hsu, Chih-Hung; Cheng, Ann-Lii

2017-01-01

Increased angiogenic activity has been demonstrated in hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC), but the mechanism was unclear. To study the role of HCV core protein, we used tube formation and Matrigel plug assays to assess the proangiogenic activity of an HCC cell line, HuH7, and 2 of its stable clones—HuH7-core-high and HuH7-core-low, with high and low HCV core protein expression, respectively. In both assays, HuH7-core-high and HuH7-core-low cells dose-dependently induced stronger angiogenesis than control cells. HuH7 cells with HCV core protein expression showed increased mRNA and protein expression of vascular endothelial growth factor (VEGF). VEGF inhibition by bevacizumab reduced the proangiogenic activity of HuH7-core-high cells. The promotor region of VEGF contains the binding site of activator protein-1 (AP-1). Compared with controls, HuH7-core-high cells had an increased AP-1 activity and nuclear localization of phospho-c-jun. AP-1 inhibition using either RNA knockdown or AP-1 inhibitors reduced the VEGF mRNA expression and the proangiogenic activity of HuH7-core-high cells. Among 131 tissue samples from HCC patients, HCV-related HCC revealed stronger VEGF expression than did hepatitis B virus-related HCC. In conclusion, increased VEGF expression through AP-1 activation is a crucial mechanism underlying the proangiogenic activity of the HCV core protein in HCC cells. PMID:29156827

Dynamic Foot Stimulation Attenuates Soleus Muscle Atrophy Induced by Hindlimb Unloading in Rats

NASA Technical Reports Server (NTRS)

Kyparos, Antonios; Feeback, Daniel L.; Layne, Charles S.; Martinez, Daniel A.; Clarke, Mark S. F.

2004-01-01

Unloading-induced myofiber atrophy is a phenomenon that occurs in the aging population, bed-ridden patients and astronauts. The objective of this study was to determine whether or not dynamic foot stimulation (DFS) applied to the plantar surface of the rat foot can serve as a countermeasure to the soleus muscle atrophy normally observed in hindlimb unloaded (HU) rats. Thirty mature adult (6-month-old) male Wistar rats were randomly assigned into ambulatory control (AMB), hindlimb unloaded alone (HU), or hindlimb unloaded with the application of DFS (HU+DFS) groups. A dynamic pattern of pressure was applied to the right foot of each HU animal using a specially fabricated boot containing an inflatable air bladder connected to a solenoid air pump controlled by a laptop computer. The anti-atrophic effects of DFS were quantified morphometrically in frozen cross-sections of soleus muscle stained using the metachromatic-ATPase fiber typing technique. Application of DFS during HU significantly counteracted the atrophic response observed in the soleus by preventing approximately 85% of the reduction in Type I myofiber cross-sectional area (CSA) observed during HU. However, DFS did not protect type II fibers of the soleus from HU-induced atrophy or any fiber type in the soleus muscle of the contralateral control leg of the DFS-treated HU animals. These results illustrate that the application of DFS to the rat foot is an effective countermeasure to soleus muscle atrophy induced by HU.

Tumor invasiveness defined by IASLC/ATS/ERS classification of ground-glass nodules can be predicted by quantitative CT parameters.

PubMed

Zhou, Qian-Jun; Zheng, Zhi-Chun; Zhu, Yong-Qiao; Lu, Pei-Ji; Huang, Jia; Ye, Jian-Ding; Zhang, Jie; Lu, Shun; Luo, Qing-Quan

2017-05-01

To investigate the potential value of CT parameters to differentiate ground-glass nodules between noninvasive adenocarcinoma and invasive pulmonary adenocarcinoma (IPA) as defined by IASLC/ATS/ERS classification. We retrospectively reviewed 211 patients with pathologically proved stage 0-IA lung adenocarcinoma which appeared as subsolid nodules, from January 2012 to January 2013 including 137 pure ground glass nodules (pGGNs) and 74 part-solid nodules (PSNs). Pathological data was classified under the 2011 IASLC/ATS/ERS classification. Both quantitative and qualitative CT parameters were used to determine the tumor invasiveness between noninvasive adenocarcinomas and IPAs. There were 154 noninvasive adenocarcinomas and 57 IPAs. In pGGNs, CT size and area, one-dimensional mean CT value and bubble lucency were significantly different between noninvasive adenocarcinomas and IPAs on univariate analysis. Multivariate regression and ROC analysis revealed that CT size and one-dimensional mean CT value were predictive of noninvasive adenocarcinomas compared to IPAs. Optimal cutoff value was 13.60 mm (sensitivity, 75.0%; specificity, 99.6%), and -583.60 HU (sensitivity, 68.8%; specificity, 66.9%). In PSNs, there were significant differences in CT size and area, solid component area, solid proportion, one-dimensional mean and maximum CT value, three-dimensional (3D) mean CT value between noninvasive adenocarcinomas and IPAs on univariate analysis. Multivariate and ROC analysis showed that CT size and 3D mean CT value were significantly differentiators. Optimal cutoff value was 19.64 mm (sensitivity, 53.7%; specificity, 93.9%), -571.63 HU (sensitivity, 85.4%; specificity, 75.8%). For pGGNs, CT size and one-dimensional mean CT value are determinants for tumor invasiveness. For PSNs, tumor invasiveness can be predicted by CT size and 3D mean CT value.

China and United Nations Peacekeeping Operations in Africa

DTIC Science & Technology

2007-01-01

November 2006 China-Africa Economic Forum , hosted by Beijing and attended by forty-eight African nations, President Hu promised that China would...scholarships to four thousand African students, and develop increasingly closer ties over the succeeding decade.7 This forum and China’s actions with...and Eritrea (UNMEE), Liberia (UNMIL), Sudan (UNMIS), Sierra Leone (UNIOSIL), and the Western Sahara (MINURSO, discussed at length below). The Chinese

Methylselenium and Prostate Cancer Apoptosis

DTIC Science & Technology

2008-02-01

Page C , Hu C , Nunez G, BakerV. Bcl-xL is expressed in ovarian carcinoma and modu- lates chemotherapy-induced apoptosis. Gynecol Oncol1998;70:398^403...WORK UNIT NUMBER 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS( ES ) 8. PERFORMING ORGANIZATION REPORT NUMBER University of Minnesota...Austin, MN 55912 9. SPONSORING / MONITORING AGENCY NAME(S) AND ADDRESS( ES ) 10. SPONSOR/MONITOR’S ACRONYM(S) U.S. Army Medical

Positive feedback between RNA-binding protein HuD and transcription factor SATB1 promotes neurogenesis.

PubMed

Wang, Feifei; Tidei, Joseph J; Polich, Eric D; Gao, Yu; Zhao, Huashan; Perrone-Bizzozero, Nora I; Guo, Weixiang; Zhao, Xinyu

2015-09-08

The mammalian embryonic lethal abnormal vision (ELAV)-like protein HuD is a neuronal RNA-binding protein implicated in neuronal development, plasticity, and diseases. Although HuD has long been associated with neuronal development, the functions of HuD in neural stem cell differentiation and the underlying mechanisms have gone largely unexplored. Here we show that HuD promotes neuronal differentiation of neural stem/progenitor cells (NSCs) in the adult subventricular zone by stabilizing the mRNA of special adenine-thymine (AT)-rich DNA-binding protein 1 (SATB1), a critical transcriptional regulator in neurodevelopment. We find that SATB1 deficiency impairs the neuronal differentiation of NSCs, whereas SATB1 overexpression rescues the neuronal differentiation phenotypes resulting from HuD deficiency. Interestingly, we also discover that SATB1 is a transcriptional activator of HuD during NSC neuronal differentiation. In addition, we demonstrate that NeuroD1, a neuronal master regulator, is a direct downstream target of SATB1. Therefore, HuD and SATB1 form a positive regulatory loop that enhances NeuroD1 transcription and subsequent neuronal differentiation. Our results here reveal a novel positive feedback network between an RNA-binding protein and a transcription factor that plays critical regulatory roles in neurogenesis.

HU-331, a novel cannabinoid-based anticancer topoisomerase II inhibitor.

PubMed

Kogan, Natalya M; Schlesinger, Michael; Priel, Esther; Rabinowitz, Ruth; Berenshtein, Eduard; Chevion, Mordechai; Mechoulam, Raphael

2007-01-01

Anthracyclines, a large group of quinonoid compounds, are used to treat some forms of cancer. Although highly effective in cancer therapy, the mechanism of action of these compounds is not specific; they act on cancer and other cells by numerous mechanisms. A new anticancer quinone (HU-331) was synthesized from cannabidiol. It shows significant high efficacy against human cancer cell lines in vitro and against in vivo tumor grafts in nude mice. In this study, we investigated its mode of action and present evidence on its unique mechanism. HU-331 does not cause cancer cell cycle arrest, cell apoptosis, or caspase activation. HU-331-caused cell death of human cancer cell lines is not mediated by reactive oxygen intermediates/species, as exposure to HU-331 failed to elicit the generation of reactive oxygen species. HU-331 inhibits DNA topoisomerase II even at nanomolar concentrations but has only a slight nonsignificant effect on DNA topoisomerase I action. The cannabinoid quinone HU-331 is a highly specific inhibitor of topoisomerase II, compared with most known anticancer quinones. It might represent a new potent anticancer drug.

Assessment of in vitro cyto/genotoxicity of sequentially treated electroplating effluent on the human hepatocarcinoma HuH-7 cell line.

PubMed

Naik, Umesh Chandra; Das, Mihir Tanay; Sauran, Swati; Thakur, Indu Shekhar

2014-03-01

The present study compares in vitro toxicity of electroplating effluent after the batch treatment process with that obtained after the sequential treatment process. Activated charcoal prepared from sugarcane bagasse through chemical carbonization, and tolerant indigenous bacteria, Bacillus sp. strain IST105, were used individually and sequentially for the treatment of electroplating effluent. The sequential treatment involving activated charcoal followed by bacterial treatment removed 99% of Cr(VI) compared with the batch processes, which removed 40% (charcoal) and 75% (bacteria), respectively. Post-treatment in vitro cyto/genotoxicity was evaluated by the MTT test and the comet assay in human HuH-7 hepatocarcinoma cells. The sequentially treated sample showed an increase in LC50 value with a 6-fold decrease in comet-assay DNA migration compared with that of untreated samples. A significant decrease in DNA migration and an increase in LC50 value of treated effluent proved the higher effectiveness of the sequential treatment process over the individual batch processes. Copyright © 2014 Elsevier B.V. All rights reserved.

A Trauma Doctor's Practice in Nineteenth-century China: The Medical Cases of Hu Tingguang.

PubMed

Wu, Yi-Li

2017-05-01

This paper analyses the medical activities of Hu Tingguang, an early nineteenth-century Chinese healer who specialized in treating traumatic injuries. Hu aimed to improve the state of medical knowledge about injuries by writing a comprehensive treatise titled Compilation of Teachings on Traumatology , completed in 1815. This work notably included a set of medical cases describing the experiences of Hu and his father, which Hu used to teach readers how to employ and adapt different therapies: bone setting, petty surgery, and drugs. By examining how Hu dealt with different forms of damage to the body's material form, this paper shows how manual therapies could be a focus of medical creativity and innovation. It also contributes to a growing corpus of scholarship exploring the way that awareness of and concern with the structure of the body historically shaped Chinese medical thought and practice.

A Trauma Doctor’s Practice in Nineteenth-century China: The Medical Cases of Hu Tingguang

PubMed Central

Wu, Yi-Li

2017-01-01

Summary This paper analyses the medical activities of Hu Tingguang, an early nineteenth-century Chinese healer who specialized in treating traumatic injuries. Hu aimed to improve the state of medical knowledge about injuries by writing a comprehensive treatise titled Compilation of Teachings on Traumatology, completed in 1815. This work notably included a set of medical cases describing the experiences of Hu and his father, which Hu used to teach readers how to employ and adapt different therapies: bone setting, petty surgery, and drugs. By examining how Hu dealt with different forms of damage to the body’s material form, this paper shows how manual therapies could be a focus of medical creativity and innovation. It also contributes to a growing corpus of scholarship exploring the way that awareness of and concern with the structure of the body historically shaped Chinese medical thought and practice. PMID:29075051

Modeling electrostatic and heterogeneity effects on proton dissociation from humic substances

USGS Publications Warehouse

Tipping, E.; Reddy, M.M.; Hurley, M.A.

1990-01-01

The apparent acid dissociation constant of humic substances increases by 2-4 pK units as ionization of the humic carboxylate groups proceeds. This change in apparent acid strength is due in part to the increase in electrical charge on the humic molecules as protons are shed. In addition, proton dissociation reactions are complicated because humic substances are heterogeneous with respect to proton dissociating groups and molecular size. In this paper, we use the Debye-Hu??ckel theory to describe the effects of electrostatic interactions on proton dissociation of humic substances. Simulations show that, for a size-heterogeneous system of molecules, the weight-average molecular weight is preferable to the number-average value for averaging the effects of electrostatic interactions. Analysis of published data on the proton dissociation of fulvic acid from the Suwannee River shows that the electrostatic interactions can be satisfactorily described by a hypothetical homogeneous compound having a molecular weight of 1000 (similar to the experimentally determined weight-average value). Titration data at three ionic strengths, for several fulvic acid concentrations, and in the pH range from 2.9 to 6.4 can be fitted with three adjustable parameters (pK??int values), given information on molecular size and carboxylate group content. ?? 1990 American Chemical Society.

Stimulating angiogenesis mitigates the unloading-induced reduction in osteogenesis in early-stage bone repair in rats.

PubMed

Matsumoto, Takeshi; Sato, Shota

2015-03-01

Accelerating fracture healing during bed rest allows early mobilization and avoids prolonged fracture healing times. We tested the hypothesis that stimulating angiogenesis with deferoxamine (DFO) mitigates the unloading-induced reduction in early-stage bone repair. Rats aged 12 weeks were subjected to cortical drilling on their tibial diaphysis under anesthesia and treated with hindlimb unloading (HU), HU and DFO administration (DFOHU), or weight bearing (WB) for 5 or 10 days (HU5/10, DFOHU5/10, WB5/10; n = 8 per groups) until sacrifice for vascular casting with a zirconium dioxide-based contrast agent. Taking advantage of its absorption discontinuity at the K-absorption edge, vascular and bone images in the drill-hole defects were acquired by synchrotron radiation subtraction CT. Bone repair was reduced in HU rats. The bone volume fraction (B.Vf) was 88% smaller in HU5 and 42% smaller in HU10 than in WB5/10. The bone segment densities (B.Seg) were 97% smaller in HU5 and 141% larger in HU10 than in WB5/10, and bone thickness (B.Th) was 38% smaller in HU10 than in WB10. The vascular volume fraction (V.Vf) was 35% and the mean vessel diameter (V.D) was 13% smaller in HU10 than in WB10. When compared according to categorized vessel sizes, V.Vf in the diameter ranges 20-30, 30-40, and >40 μm were smaller in HU10 than in WB10, and V.Seg in the diameter range >40 μm was smaller in HU10 than in WB10. In contrast, there was no difference in B.Vf between DFOHU5/10 and WB5/10 and in V.Vf between DFOHU10 and WB10, though B.Seg remained 86% smaller in DFOHU5 and 94% larger in DFOHU10 than in WB5/10, and B.Th and V.D were 23% and 14% lower in DFOHU10 than in WB10. Vessel size-specific V.Vf in the diameter ranges 10-20 and 20-30 μm was larger in DFOHU5 than in HU5. In conclusion, the enhanced angiogenic ingrowth mitigates the reduction in bone repair during mechanical unloading. © 2015 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

HuD and the Survival Motor Neuron Protein Interact in Motoneurons and Are Essential for Motoneuron Development, Function, and mRNA Regulation.

PubMed

Hao le, Thi; Duy, Phan Q; An, Min; Talbot, Jared; Iyer, Chitra C; Wolman, Marc; Beattie, Christine E

2017-11-29

Motoneurons establish a critical link between the CNS and muscles. If motoneurons do not develop correctly, they cannot form the required connections, resulting in movement defects or paralysis. Compromised development can also lead to degeneration because the motoneuron is not set up to function properly. Little is known, however, regarding the mechanisms that control vertebrate motoneuron development, particularly the later stages of axon branch and dendrite formation. The motoneuron disease spinal muscular atrophy (SMA) is caused by low levels of the survival motor neuron (SMN) protein leading to defects in vertebrate motoneuron development and synapse formation. Here we show using zebrafish as a model system that SMN interacts with the RNA binding protein (RBP) HuD in motoneurons in vivo during formation of axonal branches and dendrites. To determine the function of HuD in motoneurons, we generated zebrafish HuD mutants and found that they exhibited decreased motor axon branches, dramatically fewer dendrites, and movement defects. These same phenotypes are present in animals expressing low levels of SMN, indicating that both proteins function in motoneuron development. HuD binds and transports mRNAs and one of its target mRNAs, Gap43 , is involved in axonal outgrowth. We found that Gap43 was decreased in both HuD and SMN mutants. Importantly, transgenic expression of HuD in motoneurons of SMN mutants rescued the motoneuron defects, the movement defects, and Gap43 mRNA levels. These data support that the interaction between SMN and HuD is critical for motoneuron development and point to a role for RBPs in SMA. SIGNIFICANCE STATEMENT In zebrafish models of the motoneuron disease spinal muscular atrophy (SMA), motor axons fail to form the normal extent of axonal branches and dendrites leading to decreased motor function. SMA is caused by low levels of the survival motor neuron (SMN) protein. We show in motoneurons in vivo that SMN interacts with the RNA binding protein, HuD. Novel mutants reveal that HuD is also necessary for motor axonal branch and dendrite formation. Data also revealed that both SMN and HuD affect levels of an mRNA involved in axonal growth. Moreover, expressing HuD in SMN-deficient motoneurons can rescue the motoneuron development and motor defects caused by low levels of SMN. These data support that SMN:HuD complexes are essential for normal motoneuron development and indicate that mRNA handling is a critical component of SMA. Copyright © 2017 the authors 0270-6474/17/3711559-13$15.00/0.

Improvement of anemia in W/WV mice by recombinant human erythropoietin (rHuEPO) mediated through EPO receptors with lowered affinity.

PubMed

Kabaya, K; Akiyama, H; Nishi, N; Misaizu, T; Okada, Y; Kawagishi, M; Amano, K; Kusaka, M; Seki, M; Uzumaki, H

1995-01-01

We studied the effects of recombinant human erythropoietin (rHuEPO) on anemic W/WV mice which manifested severe anemia accompanied by mutation of the W gene encoding tyrosine kinase type receptor (c-kit gene) of bone marrow hematopoietic cells. Nine-week-old male W/WV mice or normal littermates (+/+) were used. Since serum EPO concentration in W/WV mice increased in proportion to severity of anemia, EPO production in the kidneys of these animals was found to be regulated normally. Hematocrit in +/+ mice increased and a maximal response was also obtained with 2,000 IU/kg of rHuEPO. On the other hand, hematocrit in W/WV mice increased in a dose-responsive manner by administration with 2,000 and 10,000 IU/kg, showing different responses to rHuEPO in these two types of mice. The responsiveness of W/WV mice to rHuEPO was low in terms of increases in erythroblastic precursor cells (CFU-E), and immature cells in the bone marrow. Scatchard analysis of the specific binding of 125I-rHuEPO against bone marrow cells revealed that the different responsiveness to rHuEPO between W/WV and +/+ mice may be correlated with differences in affinity of EPO receptor of bone marrow cells in these mice. From these results, a high dose of rHuEPO is capable of improving the anemia in W/WV mice that had EPO receptors with lowered affinity, indicating the possible effectiveness of rHuEPO in anemic patients with EPO receptor abnormality.

Bone mineralization changes of the glenoid in shoulders with symptomatic rotator cuff tear.

PubMed

Harada, Yohei; Yokoya, Shin; Akiyama, Yuji; Mochizuki, Yu; Ochi, Mitsuo; Adachi, Nobuo

2018-06-06

Computed tomography osteoabsorptiometry (CTO) is a method to analyze the stress distribution in joints by measuring the subchondral bone density. The purpose of this study was to evaluate the bone mineralization changes of the glenoid in shoulders with rotator cuff tears by CTO and to evaluate whether rotator cuff tears are associated with stress changes in the glenoid. In total, 32 patients, who were diagnosed with unilateral rotator cuff tears and underwent arthroscopic rotator cuff repair, were enrolled in this study. They underwent CT scanning of both shoulders pre-operatively and the glenoid was evaluated using CTO. Hounsfield units (HU) in seven areas of the glenoid were compared between the affected and unaffected sides. The central area of the glenoid on the affected side had significantly lower HU than on the unaffected side among all patients. Focusing on the rotator cuff tear size and the subscapularis tendon, only patients with larger cuff tears or with subscapularis tendon tears showed significantly lower HU in the central area of the affected side. This study showed a decrease in bone mineralization density in the central glenoid in shoulders with rotator cuff tear. This change was observed in the case of larger cuff tears and subscapularis tendon tears. Our results help clarify the changes in stress distribution in the shoulder joint caused by symptomatic rotator cuff tears.

Imaging Characteristics of Pathologically Proven Thymic Hyperplasia: Identifying Features That Can Differentiate True From Lymphoid Hyperplasia

PubMed Central

Araki, Tetsuro; Sholl, Lynette M.; Gerbaudo, Victor H.; Hatabu, Hiroto; Nishino, Mizuki

2014-01-01

OBJECTIVE The purpose of this article is to investigate the imaging characteristics of pathologically proven thymic hyperplasia and to identify features that can differentiate true hyperplasia from lymphoid hyperplasia. MATERIALS AND METHODS Thirty-one patients (nine men and 22 women; age range, 20–68 years) with pathologically confirmed thymic hyperplasia (18 true and 13 lymphoid) who underwent preoperative CT (n = 27), PET/CT (n = 5), or MRI (n = 6) were studied. The length and thickness of each thymic lobe and the transverse and anterior-posterior diameters and attenuation of the thymus were measured on CT. Thymic morphologic features and heterogeneity on CT and chemical shift on MRI were evaluated. Maximum standardized uptake values were measured on PET. Imaging features between true and lymphoid hyperplasia were compared. RESULTS No significant differences were observed between true and lymphoid hyperplasia in terms of thymic length, thickness, diameters, morphologic features, and other qualitative features (p > 0.16). The length, thickness, and diameters of thymic hyperplasia were significantly larger than the mean values of normal glands in the corresponding age group (p < 0.001). CT attenuation of lymphoid hyperplasia was significantly higher than that of true hyperplasia among 15 patients with contrast-enhanced CT (median, 47.9 vs 31.4 HU; Wilcoxon p = 0.03). The receiver operating characteristic analysis yielded greater than 41.2 HU as the optimal threshold for differentiating lymphoid hyperplasia from true hyperplasia, with 83% sensitivity and 89% specificity. A decrease of signal intensity on opposed-phase images was present in all four cases with in- and opposed-phase imaging. The mean maximum standardized uptake value was 2.66. CONCLUSION CT attenuation of the thymus was significantly higher in lymphoid hyperplasia than in true hyperplasia, with an optimal threshold of greater than 41.2 HU in this cohort of patients with pathologically confirmed thymic hyperplasia. PMID:24555583

DOE Office of Scientific and Technical Information (OSTI.GOV)

Thomas, S; Yuen, C; Huang, V

Purpose: In this abstract we implement and validate a 4D VMAT Acuros XB dose calculation using Gafchromic film. Special attention is paid to the physical material assignment in the CT dataset and to reported dose to water and dose to medium. Methods: A QUASAR phantom with a 3 cm sinusoidal tumor motion and 5 second period was scanned using 4D computed tomography. A CT was also obtained of the static QUASAR phantom with the tumor at the central position. A VMAT plan was created on the average CT dataset and was delivered on a Varian TrueBeam linear accelerator. The trajectorymore » log file from this treatment was acquired and used to create 10 VMAT subplans (one for each portion of the breathing cycle). Motion for each subplan was simulated by moving the beam isocentre in the superior/inferior direction in the Treatment Planning System on the static CT scan. The 10 plans were calculated (both dose to medium and dose to water) and summed for 1) the original HU values from the static CT scan and 2) the correct physical material assignment in the CT dataset. To acquire a breathing phase synchronized film measurements the trajectory log was used to create a VMAT delivery plan which includes dynamic couch motion using the Developer Mode. Three different treatment start phases were investigated (mid inhalation, full inhalation and full exhalation). Results: For each scenario the coronal dose distributions were measured using Gafchromic film and compared to the corresponding calculation with Film QA Pro Software using a Gamma test with a 3%/3mm distance to agreement criteria. Good agreement was found between calculation and measurement. No statistically significant difference in agreement was found between calculations to original HU values vs calculations to over-written (material-assigned) HU values. Conclusion: The investigated 4D dose calculation method agrees well with measurement.« less

Effect of Age on Energy Requirement for Maintenance and Growth of Dorper and Hu Crossbred F1 Ewes Weighing 20 to 50 kg

PubMed Central

Nie, H. T.; Wan, Y. J.; You, J. H.; Wang, Z. Y.; Lan, S.; Fan, Y. X.; Wang, F.

2015-01-01

This research aimed to define the energy requirement of Dorper and Hu Hybrid F1 ewes 20 to 50 kg of body weight, furthermore to study energy requirement changes with age and evaluate the effect of age on energy requirement parameters. In comparative slaughter trial, thirty animals were divided into three dry matter intake treatments (ad libitum, n = 18; low restricted, n = 6; high restricted, n = 6), and were all slaughtered as baseline, intermediate, and final slaughter groups, to calculate body chemical components and energy retained. In digestibility trial, twelve ewes were housed in individual metabolic cages and randomly assigned to three feeding treatments in accordance with the design of a comparative slaughter trial, to evaluate dietary energetic values at different feed intake levels. The combined data indicated that, with increasing age, the net energy requirement for maintenance (NEm) decreased from 260.62±13.21 to 250.61±11.79 kJ/kg0.75 of shrunk body weight (SBW)/d, and metabolizable energy requirement for maintenance (MEm) decreased from 401.99±20.31 to 371.23±17.47 kJ/kg0.75 of SBW/d. Partial efficiency of ME utilization for maintenance (km, 0.65 vs 0.68) and growth (kg, 0.42 vs 0.41) did not differ (p>0.05) due to age; At the similar condition of average daily gain, net energy requirements for growth (NEg) and metabolizable energy requirements for growth (MEg) for ewes during late fattening period were 23% and 25% greater than corresponding values of ewes during early fattening period. In conclusion, the effect of age upon energy requirement parameters in the present study were similar in tendency with previous recommendations, values of energy requirement for growth (NEg and MEg) for Dorper and Hu crossbred female lambs ranged between the NRC (2007) recommendation for early and later maturating growing sheep. PMID:26104522

Optimization of PMAxx pretreatment to distinguish between human norovirus with intact and altered capsids in shellfish and sewage samples.

PubMed

Randazzo, Walter; Khezri, Mohammad; Ollivier, Joanna; Le Guyader, Françoise S; Rodríguez-Díaz, Jesús; Aznar, Rosa; Sánchez, Gloria

2018-02-02

Shellfish contamination by human noroviruses (HuNoVs) is a serious health and economic problem. Recently an ISO procedure based on RT-qPCR for the quantitative detection of HuNoVs in shellfish has been issued, but these procedures cannot discriminate between inactivated and potentially infectious viruses. The aim of the present study was to optimize a pretreatment using PMAxx to better discriminate between intact and heat-treated HuNoVs in shellfish and sewage. To this end, the optimal conditions (30min incubation with 100μM of PMAxx and 0.5% of Triton, and double photoactivation) were applied to mussels, oysters and cockles artificially inoculated with thermally-inactivated (99°C for 5min) HuNoV GI and GII. This pretreatment reduced the signal of thermally-inactivated HuNoV GI in cockles and HuNoV GII in mussels by >3 log. Additionally, this pretreatment reduced the signal of thermally-inactivated HuNoV GI and GII between 1 and 1.5 log in oysters. Thermal inactivation of HuNoV GI and GII in PBS, sewage and bioaccumulated oysters was also evaluated by the PMAxx-Triton pretreatment. Results showed significant differences between reductions observed in the control and PMAxx-treated samples in PBS following treatment at 72 and 95°C for 15min. In sewage, the RT-qPCR signal of HuNoV GI was completely removed by the PMAxx pretreatment after heating at 72 and 95°C, while the RT-qPCR signal for HuNoV GII was completely eliminated only at 95°C. Finally, the PMAxx-Triton pretreatment was applied to naturally contaminated sewage and oysters, resulting in most of the HuNoV genomes quantified in sewage and oyster samples (12 out of 17) corresponding to undamaged capsids. Although this procedure may still overestimate infectivity, the PMAxx-Triton pretreatment represents a step forward to better interpret the quantification of intact HuNoVs in complex matrices, such as sewage and shellfish, and it could certainly be included in the procedures based on RT-qPCR. Copyright © 2017 Elsevier B.V. All rights reserved.

New Aspects of the Interplay between Penicillin Binding Proteins, murM, and the Two-Component System CiaRH of Penicillin-Resistant Streptococcus pneumoniae Serotype 19A Isolates from Hungary.

PubMed

Schweizer, Inga; Blättner, Sebastian; Maurer, Patrick; Peters, Katharina; Vollmer, Daniela; Vollmer, Waldemar; Hakenbeck, Regine; Denapaite, Dalia

2017-07-01

The Streptococcus pneumoniae clone Hungary 19A -6 expresses unusually high levels of β-lactam resistance, which is in part due to mutations in the MurM gene, encoding a transferase involved in the synthesis of branched peptidoglycan. Moreover, it contains the allele ciaH232 , encoding the histidine kinase CiaH (M. Müller, P. Marx, R. Hakenbeck, and R. Brückner, Microbiology 157:3104-3112, 2011, https://doi.org/10.1099/mic.0.053157-0). High-level penicillin resistance primarily requires the presence of low-affinity (mosaic) penicillin binding protein (PBP) genes, as, for example, in strain Hu17, a closely related member of the Hungary 19A -6 lineage. Interestingly, strain Hu15 is β-lactam sensitive due to the absence of mosaic PBPs. This unique situation prompted us to investigate the development of cefotaxime resistance in transformation experiments with genes known to play a role in this phenotype, pbp2x , pbp1a , murM , and ciaH , and penicillin-sensitive recipient strains R6 and Hu15. Characterization of phenotypes, peptidoglycan composition, and CiaR-mediated gene expression revealed several novel aspects of penicillin resistance. The murM gene of strain Hu17 ( murM Hu17 ), which is highly similar to murM of Streptococcus mitis , induced morphological changes which were partly reversed by ciaH232. murM Hu17 conferred cefotaxime resistance only in the presence of the pbp2x o f strain Hu17 ( pbp2x Hu17 ). The ciaH232 allele contributed to a remarkable increase in cefotaxime resistance in combination with pbp2x Hu17 and pbp1a of strain Hu17 ( pbp1a Hu17 ), accompanied by higher levels of expression of CiaR-regulated genes, documenting that ciaH232 responds to PBP1a Hu17 -mediated changes in cell wall synthesis. Most importantly, the proportion of branched peptides relative to the proportion of linear muropeptides increased in cells containing mosaic PBPs, suggesting an altered enzymatic activity of these proteins. Copyright © 2017 Schweizer et al.

Nanosystems based on siRNA silencing HuR expression counteract diabetic retinopathy in rat.

PubMed

Amadio, Marialaura; Pascale, Alessia; Cupri, Sarha; Pignatello, Rosario; Osera, Cecilia; D Agata, Velia; D Amico, Agata Grazia; Leggio, Gian Marco; Ruozi, Barbara; Govoni, Stefano; Drago, Filippo; Bucolo, Claudio

2016-09-01

We evaluated whether specifically and directly targeting human antigen R (HuR), a member of embryonic lethal abnormal vision (ELAV) proteins family, may represent a new potential therapeutic strategy to manage diabetic retinopathy. Nanosystems loaded with siRNA silencing HuR expression (lipoplexes), consisting of solid lipid nanoparticles (SLN) and liposomes (SUV) were prepared. Photon correlation spectroscopy analysis, Zeta potential measurement and atomic force microscopy (AFM) studies were carried out to characterize the complexation of siRNA with the lipid nanocarriers. Nanosystems were evaluated by using AFM and scanning electron microscopy. The lipoplexes were injected into the eye of streptozotocin (STZ)-induced diabetic rats. Retinal HuR and VEGF levels were detected by Western blot and ELISA, respectively. Retinal histology was also carried out. The results demonstrated that retinal HuR and VEGF are significantly increased in STZ-rats and are blunted by HuR siRNA treatment. Lipoplexes with a weak positive surface charge and with a 4:1 N/P (cationic lipid nitrogen to siRNA phosphate) ratio exert a better transfection efficiency, significantly dumping retinal HuR and VEGF levels. In conclusion, we demonstrated that siRNA can be efficiently delivered into the rat retina using lipid-based nanocarriers, and some of the lipoplexes loaded with siRNA silencing HuR expression are potential candidates to manage retinal diseases. Copyright © 2016 Elsevier Ltd. All rights reserved.