Multisite concordance of apparent diffusion coefficient measurements across the NCI Quantitative Imaging Network.

PubMed

Newitt, David C; Malyarenko, Dariya; Chenevert, Thomas L; Quarles, C Chad; Bell, Laura; Fedorov, Andriy; Fennessy, Fiona; Jacobs, Michael A; Solaiyappan, Meiyappan; Hectors, Stefanie; Taouli, Bachir; Muzi, Mark; Kinahan, Paul E; Schmainda, Kathleen M; Prah, Melissa A; Taber, Erin N; Kroenke, Christopher; Huang, Wei; Arlinghaus, Lori R; Yankeelov, Thomas E; Cao, Yue; Aryal, Madhava; Yen, Yi-Fen; Kalpathy-Cramer, Jayashree; Shukla-Dave, Amita; Fung, Maggie; Liang, Jiachao; Boss, Michael; Hylton, Nola

2018-01-01

Diffusion weighted MRI has become ubiquitous in many areas of medicine, including cancer diagnosis and treatment response monitoring. Reproducibility of diffusion metrics is essential for their acceptance as quantitative biomarkers in these areas. We examined the variability in the apparent diffusion coefficient (ADC) obtained from both postprocessing software implementations utilized by the NCI Quantitative Imaging Network and online scan time-generated ADC maps. Phantom and in vivo breast studies were evaluated for two ([Formula: see text]) and four ([Formula: see text]) [Formula: see text]-value diffusion metrics. Concordance of the majority of implementations was excellent for both phantom ADC measures and in vivo [Formula: see text], with relative biases [Formula: see text] ([Formula: see text]) and [Formula: see text] (phantom [Formula: see text]) but with higher deviations in ADC at the lowest phantom ADC values. In vivo [Formula: see text] concordance was good, with typical biases of [Formula: see text] to 3% but higher for online maps. Multiple b -value ADC implementations were separated into two groups determined by the fitting algorithm. Intergroup mean ADC differences ranged from negligible for phantom data to 2.8% for [Formula: see text] in vivo data. Some higher deviations were found for individual implementations and online parametric maps. Despite generally good concordance, implementation biases in ADC measures are sometimes significant and may be large enough to be of concern in multisite studies.

Investigation of Metabolomic Blood Biomarkers for Detection of Adenocarcinoma Lung Cancer

PubMed Central

Fahrmann, Johannes F.; Kim, Kyoungmi; DeFelice, Brian C.; Taylor, Sandra L.; Gandara, David R.; Yoneda, Ken Y.; Cooke, David T.; Fiehn, Oliver; Kelly, Karen; Miyamoto, Suzanne

2015-01-01

Background Untargeted metabolomics was utilized in case control studies of adenocarcinoma (ADC) lung cancer in order to develop and test metabolite classifiers in serum and plasma as potential biomarkers for diagnosing lung cancer. Methods Serum and plasma were collected and used in two independent case-control studies (ADC1 and ADC2). Controls were frequency matched for gender, age and smoking history. There were 52 ADC cases and 31 controls in ADC1 and 43 ADC cases and 43 controls in ADC2. Metabolomics was conducted using gas chromatography time-of-flight mass spectrometry. Differential analysis was performed on ADC1 and the top candidates (FDR < 0.05) for serum and plasma used to develop individual and multiplex-classifiers that were then tested on an independent set of serum and plasma samples (ADC2). Results Aspartate provided the best accuracy (81.4%) for an individual metabolite classifier in serum whereas pyrophosphate had the best accuracy (77.9%) in plasma when independently tested. Multiplex classifiers of either 2 or 4 serum metabolites had an accuracy of 72.7% when independently tested. For plasma, a multi-metabolite classifier consisting of 8 metabolites gave an accuracy of 77.3% when independently tested. Comparison of overall diagnostic performance between the two blood matrices yielded similar performances. However, serum is most ideal given higher sensitivity for low abundant metabolites. Conclusion This study shows the potential of metabolite-based diagnostic tests for detection of lung adenocarcinoma. Further validation in a larger pool of samples is warranted. Impact These biomarkers could improve early detection and diagnosis of lung cancer. PMID:26282632

Positron lifetime setup based on DRS4 evaluation board

NASA Astrophysics Data System (ADS)

Petriska, M.; Sojak, S.; Slugeň, V.

2014-04-01

A digital positron lifetime setup based on DRS4 evaluation board designed at the Paul Scherrer Institute has been constructed and tested in the Positron annihilation laboratory Slovak University of Technology Bratislava. The high bandwidth, low power consumption and short readout time make DRS4 chip attractive for positron annihilation lifetime (PALS) setup, replacing traditional ADCs and TDCs. A software for PALS setup online and offline pulse analysis was developed with Qt,Qwt and ALGLIB libraries.

Multi-model Analysis of Diffusion-weighted Imaging of Normal Testes at 3.0 T: Preliminary Findings.

PubMed

Min, Xiangde; Feng, Zhaoyan; Wang, Liang; Cai, Jie; Li, Basen; Ke, Zan; Zhang, Peipei; You, Huijuan; Yan, Xu

2018-04-01

This study aimed to establish diffusion quantitative parameters (apparent diffusion coefficient [ADC], DDC, α, D app , and K app ) in normal testes at 3.0 T. Sixty-four healthy volunteers in two age groups (A: 10-39 years; B: ≥ 40 years) underwent diffusion-weighted imaging scanning at 3.0 T. ADC 1000 , ADC 2000 , ADC 3000 , DDC, α, D app , and K app were calculated using the mono-exponential, stretched-exponential, and kurtosis models. The correlations between parameters and the age were analyzed. The parameters were compared between the age groups and between the right and the left testes. The average ADC 1000 , ADC 2000 , ADC 3000 , DDC, α, D app , and K app values did not significantly differ between the right and the left testes (P > .05 for all). The following significant correlations were found: positive correlations between age and testicular ADC 1000 , ADC 2000 , ADC 3000 , DDC, and D app (r = 0.516, 0.518, 0.518, 0.521, and 0.516, respectively; P < .01 for all) and negative correlations between age and testicular α and K app (r = -0.363, -0.427, respectively; P < .01 for both). Compared to group B, in group A, ADC 1000 , ADC 2000 , ADC 3000 , DDC, and D app were significantly lower (P < .05 for all), but α and K app were significantly higher (P < .05 for both). Our study demonstrated the applicability of the testicular mono-exponential, stretched-exponential, and kurtosis models. Our results can help establish a baseline for the normal testicular parameters in these diffusion models. The contralateral normal testis can serve as a suitable reference for evaluating the abnormalities of the other side. The effect of age on these parameters requires further attention. Copyright © 2018 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.

An Implementation of Physical Layer Authentication Using Software Radio

DTIC Science & Technology

2009-07-01

USRP consists of an FPGA responsible for up/down conversions, ADCs and DACs, and various plug-in daughterboards. . . . . . . . . . . . . . . . . 7 5...seen in figure 4, the USRP consists of a USB interface, a 6 field-programmable gate array ( FPGA ), ADCs and DACs, and daughterboards. The...configuration. In the following, we detail the signal receive path to highlight the design of the hardware. FPGA Receive Daughterboar d A/D A/D Tr ansmit

Histogram analysis of apparent diffusion coefficient maps for the differentiation between lymphoma and metastatic lymph nodes of squamous cell carcinoma in head and neck region.

PubMed

Wang, Yan-Jun; Xu, Xiao-Quan; Hu, Hao; Su, Guo-Yi; Shen, Jie; Shi, Hai-Bin; Wu, Fei-Yun

2018-06-01

Background To clarify the nature of cervical malignant lymphadenopathy is highly important for the diagnosis and differential diagnosis of head and neck tumors. Purpose To investigate the role of first-order apparent diffusion coefficient (ADC) histogram analysis for differentiating lymphoma from metastatic lymph nodes of squamous cell carcinoma (SCC) in the head and neck region. Material and Methods Diffusion-weighted imaging (DWI) data of 67 patients (lymphoma, n = 20; SCC, n = 47) with malignant lymphadenopathy were retrospectively analyzed. The SCC group was divided into nasopharyngeal SCC and non-nasopharyngeal SCC groups. The ADC histogram features (ADC 10 , ADC 25 , ADC mean , ADC median , ADC 75 , ADC 90 , skewness, and kurtosis) were derived and then compared by independent-samples t-test and one-way analysis of variance test, respectively. Receiver operating characteristic curve analyses were employed to investigate diagnostic performance of the significant parameters. Results Lymphoma showed significantly lower ADC mean , ADC median , ADC 75 , and ADC 90 than SCC (all P < 0.05). Setting ADC 90  = 0.719 × 10 -3  mm 2 /s as the threshold value, optimal diagnostic performance was achieved (area under the curve [AUC] = 0.719, sensitivity = 95.7%, specificity = 50.0%). Subgroup analyses showed no significant difference between lymphoma and NPC (all P > 0.05). Lymphoma showed significantly lower ADC 25 , ADC mean , ADC median , ADC 75 , and ADC 90 than non-nasopharyngeal SCC (all P < 0.05). Optimal diagnostic performance (AUC = 0.847, sensitivity = 86.7%, specificity = 80.0%) could be achieved when setting ADC 90  = 0.943 × 10 -3  mm 2 /s as the threshold value. Conclusion Given its limitations, our study has shown that first-order ADC histogram analysis is capable of differentiating lymphoma from metastatic lymph nodes of SCC, especially those of non-nasopharyngeal SCC.

Episodic Memory in Detoxified Alcoholics: Contribution of Grey Matter Microstructure Alteration

PubMed Central

Chanraud, Sandra; Leroy, Claire; Martelli, Catherine; Kostogianni, Nikoleta; Delain, Françoise; Aubin, Henri-Jean; Reynaud, Michel; Martinot, Jean-Luc

2009-01-01

Even though uncomplicated alcoholics may likely have episodic memory deficits, discrepancies exist regarding to the integrity of brain regions that underlie this function in healthy subjects. Possible relationships between episodic memory and 1) brain microstructure assessed by magnetic resonance diffusion tensor imaging (DTI), 2) brain volumes assessed by voxel-based morphometry (VBM) were investigated in uncomplicated, detoxified alcoholics. Diffusion and morphometric analyses were performed in 24 alcohol dependent men without neurological or somatic complications and in 24 healthy men. The mean apparent coefficient of diffusion (ADC) and grey matter volumes were measured in the whole brain. Episodic memory performance was assessed using a French version of the Free and Cued Selective Reminding Test (FCSRT). Correlation analyses between verbal episodic memory, brain microstructure, and brain volumes were carried out using SPM2 software. In those with alcohol dependence, higher ADC was detected mainly in frontal, temporal and parahippocampal regions, and in the cerebellum. In alcoholics, regions with higher ADC typically also had lower grey matter volume. Low verbal episodic memory performance in alcoholism was associated with higher mean ADC in parahippocampal areas, in frontal cortex and in the left temporal cortex; no correlation was found between regional volumes and episodic memory scores. Regression analyses for the control group were not significant. These findings support the hypothesis that regional microstructural but no macrostructural alteration of the brain might be responsible, at least in part, for episodic memory deficits in alcohol dependence. PMID:19707568

Design and Testing of Space Telemetry SCA Waveform

NASA Technical Reports Server (NTRS)

Mortensen, Dale J.; Handler, Louis M.; Quinn, Todd M.

2006-01-01

A Software Communications Architecture (SCA) Waveform for space telemetry is being developed at the NASA Glenn Research Center (GRC). The space telemetry waveform is implemented in a laboratory testbed consisting of general purpose processors, field programmable gate arrays (FPGAs), analog-to-digital converters (ADCs), and digital-to-analog converters (DACs). The radio hardware is integrated with an SCA Core Framework and other software development tools. The waveform design is described from both the bottom-up signal processing and top-down software component perspectives. Simulations and model-based design techniques used for signal processing subsystems are presented. Testing with legacy hardware-based modems verifies proper design implementation and dynamic waveform operations. The waveform development is part of an effort by NASA to define an open architecture for space based reconfigurable transceivers. Use of the SCA as a reference has increased understanding of software defined radio architectures. However, since space requirements put a premium on size, mass, and power, the SCA may be impractical for today s space ready technology. Specific requirements for an SCA waveform and other lessons learned from this development are discussed.

Diagnostic accuracy of apparent diffusion coefficient and 123I-metaiodobenzylguanidine for differentiation of multiple system atrophy and Parkinson's disease.

PubMed

Umemura, Atsushi; Oeda, Tomoko; Hayashi, Ryutaro; Tomita, Satoshi; Kohsaka, Masayuki; Yamamoto, Kenji; Sawada, Hideyuki

2013-01-01

It is often hard to differentiate Parkinson's disease (PD) and parkinsonian variant of multiple system atrophy (MSA-P), especially in the early stages. Cardiac sympathetic denervation and putaminal rarefaction are specific findings for PD and MSA-P, respectively. We investigated diagnostic accuracy of putaminal apparent diffusion coefficient (ADC) test for MSA-P and (123)I-metaiodobenzylguanidine (MIBG) scintigram for PD, especially in early-stage patients. The referral standard diagnosis of PD and MSA-P were the diagnostic criteria of the United Kingdom Parkinson's Disease Society Brain Bank Criteria and the second consensus criteria, respectively. Based on the referral standard criteria, diagnostic accuracy [area under the receiver-operator characteristic curve (AUC), sensitivity and specificity] of the ADC and MIBG tests was estimated retrospectively. Diagnostic accuracy of these tests performed within 3 years of symptom onset was also investigated. ADC and MIBG tests were performed on 138 patients (20 MSA and 118 PD). AUC was 0.95 and 0.83 for the ADC and MIBG tests, respectively. Sensitivity and specificity were 85.0% and 89.0% for MSA-P diagnosis by ADC test and 67.0% and 80.0% for PD diagnosis by MIBG test. When these tests were restricted to patients with disease duration ≤ 3 years, the sensitivity and specificity were 75.0% and 91.4% for the ADC test (MSA-P diagnosis) and 47.7% and 92.3% for the MIBG test (PD diagnosis). Both tests were useful in differentiating between PD and MSA-P, even in the early stages. In early-stage patients, elevated putaminal ADC was a diagnostic marker for MSA-P. Despite high specificity of the MIBG test, careful neurological history and examinations were required for PD diagnosis because of possible false-negative results.

Radiation-hard analog-to-digital converters for space and strategic applications

NASA Technical Reports Server (NTRS)

Gauthier, M. K.; Dantas, A. R. V.

1985-01-01

During the course of the Jet Propulsion Laboratory's program to study radiation-hardened analog-to-digital converters (ADCs), numerous milestones have been reached in manufacturers' awareness and technology development and transfer, as well as in user awareness of these developments. The testing of ADCs has also continued with twenty different ADCs from seven manufacturers, all tested for total radiation dose and three tested for neutron effects. Results from these tests are reported.

PPM Receiver Implemented in Software

NASA Technical Reports Server (NTRS)

Gray, Andrew; Kang, Edward; Lay, Norman; Vilnrotter, Victor; Srinivasan, Meera; Lee, Clement

2010-01-01

A computer program has been written as a tool for developing optical pulse-position- modulation (PPM) receivers in which photodetector outputs are fed to analog-to-digital converters (ADCs) and all subsequent signal processing is performed digitally. The program can be used, for example, to simulate an all-digital version of the PPM receiver described in Parallel Processing of Broad-Band PPM Signals (NPO-40711), which appears elsewhere in this issue of NASA Tech Briefs. The program can also be translated into a design for digital PPM receiver hardware. The most notable innovation embodied in the software and the underlying PPM-reception concept is a digital processing subsystem that performs synchronization of PPM time slots, even though the digital processing is, itself, asynchronous in the sense that no attempt is made to synchronize it with the incoming optical signal a priori and there is no feedback to analog signal processing subsystems or ADCs. Functions performed by the software receiver include time-slot synchronization, symbol synchronization, coding preprocessing, and diagnostic functions. The program is written in the MATLAB and Simulink software system. The software receiver is highly parameterized and, hence, programmable: for example, slot- and symbol-synchronization filters have programmable bandwidths.

A Whole-Tumor Histogram Analysis of Apparent Diffusion Coefficient Maps for Differentiating Thymic Carcinoma from Lymphoma.

PubMed

Zhang, Wei; Zhou, Yue; Xu, Xiao-Quan; Kong, Ling-Yan; Xu, Hai; Yu, Tong-Fu; Shi, Hai-Bin; Feng, Qing

2018-01-01

To assess the performance of a whole-tumor histogram analysis of apparent diffusion coefficient (ADC) maps in differentiating thymic carcinoma from lymphoma, and compare it with that of a commonly used hot-spot region-of-interest (ROI)-based ADC measurement. Diffusion weighted imaging data of 15 patients with thymic carcinoma and 13 patients with lymphoma were retrospectively collected and processed with a mono-exponential model. ADC measurements were performed by using a histogram-based and hot-spot-ROI-based approach. In the histogram-based approach, the following parameters were generated: mean ADC (ADC mean ), median ADC (ADC median ), 10th and 90th percentile of ADC (ADC 10 and ADC 90 ), kurtosis, and skewness. The difference in ADCs between thymic carcinoma and lymphoma was compared using a t test. Receiver operating characteristic analyses were conducted to determine and compare the differentiating performance of ADCs. Lymphoma demonstrated significantly lower ADC mean , ADC median , ADC 10 , ADC 90 , and hot-spot-ROI-based mean ADC than those found in thymic carcinoma (all p values < 0.05). There were no differences found in the kurtosis ( p = 0.412) and skewness ( p = 0.273). The ADC 10 demonstrated optimal differentiating performance (cut-off value, 0.403 × 10 -3 mm 2 /s; area under the receiver operating characteristic curve [AUC], 0.977; sensitivity, 92.3%; specificity, 93.3%), followed by the ADC mean , ADC median , ADC 90 , and hot-spot-ROI-based mean ADC. The AUC of ADC 10 was significantly higher than that of the hot spot ROI based ADC (0.977 vs. 0.797, p = 0.036). Compared with the commonly used hot spot ROI based ADC measurement, a histogram analysis of ADC maps can improve the differentiating performance between thymic carcinoma and lymphoma.

An Apparent Diffusion Coefficient Histogram Method Versus a Traditional 2-Dimensional Measurement Method for Identifying Non-Puerperal Mastitis From Breast Cancer at 3.0 T.

PubMed

Tang, Qi; Li, Qiang; Xie, Dong; Chu, Ketao; Liu, Lidong; Liao, Chengcheng; Qin, Yunying; Wang, Zheng; Su, Danke

2018-05-21

This study aimed to investigate the utility of a volumetric apparent diffusion coefficient (ADC) histogram method for distinguishing non-puerperal mastitis (NPM) from breast cancer (BC) and to compare this method with a traditional 2-dimensional measurement method. Pretreatment diffusion-weighted imaging data at 3.0 T were obtained for 80 patients (NPM, n = 27; BC, n = 53) and were retrospectively assessed. Two readers measured ADC values according to 2 distinct region-of-interest (ROI) protocols. The first protocol included the generation of ADC histograms for each lesion, and various parameters were examined. In the second protocol, 3 freehand (TF) ROIs for local lesions were generated to obtain a mean ADC value (defined as ADC-ROITF). All of the ADC values were compared by an independent-samples t test or the Mann-Whitney U test. Receiver operating characteristic curves and a leave-one-out cross-validation method were also used to determine diagnostic deficiencies of the significant parameters. The ADC values for NPM were characterized by significantly higher mean, 5th to 95th percentiles, and maximum and mode ADCs compared with the corresponding ADCs for BC (all P < 0.05). However, the minimum, skewness, and kurtosis ADC values, as well as ADC-ROITF, did not significantly differ between the NPM and BC cases. Thus, the generation of volumetric ADC histograms seems to be a superior method to the traditional 2-dimensional method that was examined, and it also seems to represent a promising image analysis method for distinguishing NPM from BC.

Apparent diffusion coefficient measurement in a moving phantom simulating linear respiratory motion.

PubMed

Kwee, Thomas C; Takahara, Taro; Muro, Isao; Van Cauteren, Marc; Imai, Yutaka; Nievelstein, Rutger A J; Mali, Willem P T M; Luijten, Peter R

2010-10-01

The aim of this study was to examine the effect of simulated linear respiratory motion on apparent diffusion coefficient (ADC) measurements. Six rectangular test tubes (14 × 92 mm) filled with either water, tomato ketchup, or mayonnaise were positioned in a box containing agarose gel. This box was connected to a double-acting pneumatic cylinder, capable of inducing periodic linear motion in the long-axis direction of the magnetic bore (23-mm stroke). Diffusion-weighted magnetic resonance imaging was performed for both the static and moving phantoms, and ADC measurements were made in the six test tubes in both situations. In the three test tubes whose long axes were parallel to the direction of motion, ADCs agreed well between the moving and static phantom situations. However, in two test tubes that were filled with fluids that had a considerably lower diffusion coefficient than the surrounding agarose gel, and whose long axes were perpendicular to the direction of motion, the ADCs agreed poorly between the moving and static phantom situations. ADC measurements of large homogeneous structures are not affected by linear respiratory motion. However, ADC measurements of inhomogeneous or small structures are affected by linear respiratory motion due to partial volume effects.

Diffusion-weighted imaging: Apparent diffusion coefficient histogram analysis for detecting pathologic complete response to chemoradiotherapy in locally advanced rectal cancer.

PubMed

Choi, Moon Hyung; Oh, Soon Nam; Rha, Sung Eun; Choi, Joon-Il; Lee, Sung Hak; Jang, Hong Seok; Kim, Jun-Gi; Grimm, Robert; Son, Yohan

2016-07-01

To investigate the usefulness of apparent diffusion coefficient (ADC) values derived from histogram analysis of the whole rectal cancer as a quantitative parameter to evaluate pathologic complete response (pCR) on preoperative magnetic resonance imaging (MRI). We enrolled a total of 86 consecutive patients who had undergone surgery for rectal cancer after neoadjuvant chemoradiotherapy (CRT) at our institution between July 2012 and November 2014. Two radiologists who were blinded to the final pathological results reviewed post-CRT MRI to evaluate tumor stage. Quantitative image analysis was performed using T2 -weighted and diffusion-weighted images independently by two radiologists using dedicated software that performed histogram analysis to assess the distribution of ADC in the whole tumor. After surgery, 16 patients were confirmed to have achieved pCR (18.6%). All parameters from pre- and post-CRT ADC histogram showed good or excellent agreement between two readers. The minimum, 10th, 25th, 50th, and 75th percentile and mean ADC from post-CRT ADC histogram were significantly higher in the pCR group than in the non-pCR group for both readers. The 25th percentile value from ADC histogram in post-CRT MRI had the best diagnostic performance for detecting pCR, with an area under the receiver operating characteristic curve of 0.796. Low percentile values derived from the ADC histogram analysis of rectal cancer on MRI after CRT showed a significant difference between pCR and non-pCR groups, demonstrating the utility of the ADC value as a quantitative and objective marker to evaluate complete pathologic response to preoperative CRT in rectal cancer. J. Magn. Reson. Imaging 2016;44:212-220. © 2015 Wiley Periodicals, Inc.

A potential risk of overestimating apparent diffusion coefficient in parotid glands.

PubMed

Liu, Yi-Jui; Lee, Yi-Hsiung; Chang, Hing-Chiu; Huang, Teng-Yi; Chiu, Hui-Chu; Wang, Chih-Wei; Chiou, Ta-Wei; Hsu, Kang; Juan, Chun-Jung; Huang, Guo-Shu; Hsu, Hsian-He

2015-01-01

To investigate transient signal loss on diffusion weighted images (DWI) and overestimation of apparent diffusion coefficient (ADC) in parotid glands using single shot echoplanar DWI (EPDWI). This study enrolled 6 healthy subjects and 7 patients receiving radiotherapy. All participants received dynamic EPDWI with a total of 8 repetitions. Imaging quality of DWI was evaluated. Probability of severe overestimation of ADC (soADC), defined by an ADC ratio more than 1.2, was calculated. Error on T2WI, DWI, and ADC was computed. Statistical analysis included paired Student t testing and Mann-Whitney U test. A P value less than 0.05 was considered statistically significant. Transient signal loss was visually detected on some excitations of DWI but not on T2WI or mean DWI. soADC occurred randomly among 8 excitations and 3 directions of diffusion encoding gradients. Probability of soADC was significantly higher in radiotherapy group (42.86%) than in healthy group (24.39%). The mean error percentage decreased as the number of excitations increased on all images, and, it was smallest on T2WI, followed by DWI and ADC in an increasing order. Transient signal loss on DWI was successfully detected by dynamic EPDWI. The signal loss on DWI and overestimation of ADC could be partially remedied by increasing the number of excitations.

Drop Weight Impact Behavior of Al-Si-Cu Alloy Foam-Filled Thin-Walled Steel Pipe Fabricated by Friction Stir Back Extrusion

NASA Astrophysics Data System (ADS)

Hangai, Yoshihiko; Nakano, Yukiko; Utsunomiya, Takao; Kuwazuru, Osamu; Yoshikawa, Nobuhiro

2017-02-01

In this study, Al-Si-Cu alloy ADC12 foam-filled thin-walled stainless steel pipes, which exhibit metal bonding between the ADC12 foam and steel pipe, were fabricated by friction stir back extrusion. Drop weight impact tests were conducted to investigate the deformation behavior and mechanical properties of the foam-filled pipes during dynamic compression tests, which were compared with the results of static compression tests. From x-ray computed tomography observation, it was confirmed that the fabricated foam-filled pipes had almost uniform porosity and pore size distributions. It was found that no scattering of the fragments of collapsed ADC12 foam occurred for the foam-filled pipes owing to the existence of the pipe surrounding the ADC12 foam. Preventing the scattering of the ADC12 foam decreases the drop in stress during dynamic compression tests and therefore improves the energy absorption properties of the foam.

Test-retest reliability and repeatability of renal diffusion tensor MRI in healthy subjects.

PubMed

Cutajar, Marica; Clayden, Jonathan D; Clark, Christopher A; Gordon, Isky

2011-12-01

This study assessed test-retest reliability and repeatability of diffusion tensor imaging (DTI) in the kidneys. Seven healthy volunteers (age range, 19-31 years), were imaged three consecutive times on the same day (short-term reliability) and the same imaging protocol was repeated after a month (long-term reliability). Diffusion-weighted magnetic resonance imaging scans in the coronal-oblique projection of the kidney were acquired on a 1.5 T scanner using a multi-section echo-planar sequence; six contiguous slices each 5 mm thick, diffusion sensitisation along 20 non-collinear directions, TR=730 ms, TE=73 ms and 2 b-values (0 and 400 s mm(-2)). Volunteers were asked to hold their breath throughout each data acquisition (approx. 20 s). The apparent diffusion coefficient (ADC) and fractional anisotropy (FA) values were obtained from maps generated using dedicated software MIStar (Apollo Medical Imaging, Melbourne, Australia). Statistical analyses of both short- and long-term repeats were carried out from which the within-subject coefficient of variation (wsCV) was calculated. The wsCV obtained for both the ADC and FA values were less than 10% in all the analyses carried out. In addition, paired (repeated measures) t-test was used to measure the variation between the diffusion parameters collected from the two scanning sessions a month apart. It showed no significant difference and the wsCV obtained after comparing the first and second scans were found to be smaller than 15% for both ADC and FA. Renal DTI produces reliable and repeatable results which make longitudinal investigation of patients viable. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Diffusion-weighted MRI of the pancreas: correlation with secretin endoscopic pancreatic function test (ePFT).

PubMed

Balci, N Cem; Momtahen, Amir Javad; Akduman, E Isin; Alkaade, Samer; Bilgin, Mehmet; Burton, Frank R

2008-10-01

To evaluate the correlation between apparent diffusion coefficient (ADC) values of the pancreas on diffusion-weighted imaging (DWI) and pancreatic exocrine function determined by HCO(3) concentration in the secretin endoscopic pancreatic function test (ePFT). Mean ADC values derived from 10 different points of the pancreatic gland on DWI were reviewed in 14 patients with normal (peak HCO(3) > or = 80 mEq/L) and 14 patients with abnormal (peak HCO(3) < 80 mEq/L) ePFT results. Magnetic resonance cholangiopancreatography (MRCP) images of the same patients were evaluated for the diagnosis of chronic pancreatitis. Correlation between ADC values and HCO(3) concentration as well as Cambridge scores in MRCP was performed using Spearman's correlation test. Mean ADC value of the pancreas was 1.52 +/- 0.13 x 10(-3) mm(2)/s in patients with abnormal ePFT results and 1.78 +/- 0.07 x 10(-3) mm(2)/s in the normal group. There was a significant statistical difference between the ADC values of the pancreas in the two groups (P < .0001). There was also a statistically significant correlation between HCO(3) level and ADC value of the pancreas in the study patients (r = 0.771, P < .0001). Morphologic changes of the pancreas according to the Cambridge classification were also well correlated with the mean ADC values (r = -0.763, P < .0001). Strong correlation between ADC value and pancreatic exocrine function as well as Cambridge score for chronic pancreatitis exists. Further studies are needed to determine the cut off ADC value for chronic pancreatitis.

Radiological indeterminate vestibular schwannoma and meningioma in cerebellopontine angle area: differentiating using whole-tumor histogram analysis of apparent diffusion coefficient.

PubMed

Xu, Xiao-Quan; Li, Yan; Hong, Xun-Ning; Wu, Fei-Yun; Shi, Hai-Bin

2017-02-01

To assess the role of whole-tumor histogram analysis of apparent diffusion coefficient (ADC) maps in differentiating radiological indeterminate vestibular schwannoma (VS) from meningioma in cerebellopontine angle (CPA). Diffusion-weighted (DW) images (b = 0 and 1000 s/mm 2 ) of pathologically confirmed and radiological indeterminate CPA meningioma (CPAM) (n = 27) and VS (n = 12) were retrospectively collected and processed with mono-exponential model. Whole-tumor regions of interest were drawn on all slices of the ADC maps to obtain histogram parameters, including the mean ADC (ADC mean ), median ADC (ADC median ), 10th/25th/75th/90th percentile ADC (ADC 10 , ADC 25 , ADC 75 and ADC 90 ), skewness and kurtosis. The differences of ADC histogram parameters between CPAM and VS were compared using unpaired t-test. Multiple receiver operating characteristic (ROC) curves analysis was used to determine and compare the diagnostic value of each significant parameter. Significant differences were found on the ADC mean , ADC median , ADC 10 , ADC 25 , ADC 75 and ADC 90 between CPAM and VS (all p values < 0.001), while no significant difference was found on kurtosis (p = 0.562) and skewness (p = 0.047). ROC curves analysis revealed, a cut-off value of 1.126 × 10 -3 mm 2 /s for the ADC 90 value generated highest area under curves (AUC) for differentiating CPAM from VS (AUC, 0.975; sensitivity, 100%; specificity, 88.9%). Histogram analysis of ADC maps based on whole tumor can be a useful tool for differentiating radiological indeterminate CPAM from VS. The ADC 90 value was the most promising parameter for differentiating these two entities.

Is there a systematic bias of apparent diffusion coefficient (ADC) measurements of the breast if measured on different workstations? An inter- and intra-reader agreement study.

PubMed

Clauser, Paola; Marcon, Magda; Maieron, Marta; Zuiani, Chiara; Bazzocchi, Massimo; Baltzer, Pascal A T

2016-07-01

To evaluate the influence of post-processing systems, intra- and inter-reader agreement on the variability of apparent diffusion coefficient (ADC) measurements in breast lesions. Forty-one patients with 41 biopsy-proven breast lesions gave their informed consent and were included in this prospective IRB-approved study. Magnetic resonance imaging (MRI) examinations were performed at 1.5 T using an EPI-DWI sequence, with b-values of 0 and 1000 s/mm(2). Two radiologists (R1, R2) reviewed the images in separate sessions and measured the ADC for lesion, using MRI-workstation (S-WS), PACS-workstation (P-WS) and a commercial DICOM viewer (O-SW). Agreement was evaluated using the intraclass correlation coefficient (ICC), Bland-Altman plots and coefficient of variation (CV). Thirty-one malignant, two high-risk and eight benign mass-like lesions were analysed. Intra-reader agreement was almost perfect (ICC-R1 = 0.974; ICC-R2 = 0.990) while inter-reader agreement was substantial (ICC from 0.615 to 0.682). Bland-Altman plots revealed a significant bias in ADC values measured between O-SW and S-WS (P = 0.025), no further systematic differences were identified. CV varied from 6.8 % to 7.9 %. Post-processing systems may have a significant, although minor, impact on ADC measurements in breast lesions. While intra-reader agreement is high, the main source of ADC variability seems to be caused by inter-reader variation. • ADC provides quantitative information on breast lesions independent from the system used. • ADC measurement using different workstations and software systems is generally reliable. • Systematic, but minor, differences may occur between different post-processing systems. • Inter-reader agreement of ADC measurements exceeded intra-reader agreement.

Enhancing tumor apparent diffusion coefficient histogram skewness stratifies the postoperative survival in recurrent glioblastoma multiforme patients undergoing salvage surgery.

PubMed

Zolal, Amir; Juratli, Tareq A; Linn, Jennifer; Podlesek, Dino; Sitoci Ficici, Kerim Hakan; Kitzler, Hagen H; Schackert, Gabriele; Sobottka, Stephan B; Rieger, Bernhard; Krex, Dietmar

2016-05-01

Objective To determine the value of apparent diffusion coefficient (ADC) histogram parameters for the prediction of individual survival in patients undergoing surgery for recurrent glioblastoma (GBM) in a retrospective cohort study. Methods Thirty-one patients who underwent surgery for first recurrence of a known GBM between 2008 and 2012 were included. The following parameters were collected: age, sex, enhancing tumor size, mean ADC, median ADC, ADC skewness, ADC kurtosis and fifth percentile of the ADC histogram, initial progression free survival (PFS), extent of second resection and further adjuvant treatment. The association of these parameters with survival and PFS after second surgery was analyzed using log-rank test and Cox regression. Results Using log-rank test, ADC histogram skewness of the enhancing tumor was significantly associated with both survival (p = 0.001) and PFS after second surgery (p = 0.005). Further parameters associated with prolonged survival after second surgery were: gross total resection at second surgery (p = 0.026), tumor size (0.040) and third surgery (p = 0.003). In the multivariate Cox analysis, ADC histogram skewness was shown to be an independent prognostic factor for survival after second surgery. Conclusion ADC histogram skewness of the enhancing lesion, enhancing lesion size, third surgery, as well as gross total resection have been shown to be associated with survival following the second surgery. ADC histogram skewness was an independent prognostic factor for survival in the multivariate analysis.

Smart Antenna UKM Testbed for Digital Beamforming System

NASA Astrophysics Data System (ADS)

Islam, Mohammad Tariqul; Misran, Norbahiah; Yatim, Baharudin

2009-12-01

A new design of smart antenna testbed developed at UKM for digital beamforming purpose is proposed. The smart antenna UKM testbed developed based on modular design employing two novel designs of L-probe fed inverted hybrid E-H (LIEH) array antenna and software reconfigurable digital beamforming system (DBS). The antenna is developed based on using the novel LIEH microstrip patch element design arranged into [InlineEquation not available: see fulltext.] uniform linear array antenna. An interface board is designed to interface to the ADC board with the RF front-end receiver. The modular concept of the system provides the capability to test the antenna hardware, beamforming unit, and beamforming algorithm in an independent manner, thus allowing the smart antenna system to be developed and tested in parallel, hence reduces the design time. The DBS was developed using a high-performance [InlineEquation not available: see fulltext.] floating-point DSP board and a 4-channel RF front-end receiver developed in-house. An interface board is designed to interface to the ADC board with the RF front-end receiver. A four-element receiving array testbed at 1.88-2.22 GHz frequency is constructed, and digital beamforming on this testbed is successfully demonstrated.

Antibody responses to prime-boost vaccination with an HIV-1 gp145 envelope protein and chimpanzee adenovirus vectors expressing HIV-1 gp140.

PubMed

Emmer, Kristel L; Wieczorek, Lindsay; Tuyishime, Steven; Molnar, Sebastian; Polonis, Victoria R; Ertl, Hildegund C J

2016-10-23

Over 2 million individuals are infected with HIV type 1 (HIV-1) each year, yet an effective vaccine remains elusive. The most successful HIV-1 vaccine to date demonstrated 31% efficacy. Immune correlate analyses associated HIV-1 envelope (Env)-specific antibodies with protection, thus providing a path toward a more effective vaccine. We sought to test the antibody response from novel prime-boost vaccination with a chimpanzee-derived adenovirus (AdC) vector expressing a subtype C Env glycoprotein (gp)140 combined with either a serologically distinct AdC vector expressing gp140 of a different subtype C isolate or an alum-adjuvanted, partially trimeric gp145 from yet another subtype C isolate. Three different prime-boost regimens were tested in mice: AdC prime-protein boost, protein prime-AdC boost, and AdC prime-AdC boost. Each regimen was tested at two different doses of AdC vector in a total of six experimental groups. Sera were collected at various time points and evaluated by ELISA for Env-specific antibody binding, isotype, and avidity. Antibody functionality was assessed by pseudovirus neutralization assay. Priming with AdC followed by a protein boost or sequential immunizations with two AdC vectors induced HIV-1 Env-specific binding antibodies, including those to the variable region 2, whereas priming with protein followed by an AdC boost was relatively ineffective. Antibodies that cross-neutralized tier 1 HIV-1 from different subtypes were elicited with vaccine regimens that included immunizations with protein. Our study warrants further investigation of AdC vector and gp145 protein prime-boost vaccines and their ability to protect against acquisition in animal challenge studies.

Normalization of ADC does not improve correlation with overall survival in patients with high-grade glioma (HGG).

PubMed

Qin, Lei; Li, Angie; Qu, Jinrong; Reinshagen, Katherine; Li, Xiang; Cheng, Su-Chun; Bryant, Annie; Young, Geoffrey S

2018-04-01

Mixed reports leave uncertainty about whether normalization of apparent diffusion coefficient (ADC) to a within-subject white matter reference is necessary for assessment of tumor cellularity. We tested whether normalization improves the previously reported correlation of resection margin ADC with 15-month overall survival (OS) in HGG patients. Spin-echo echo-planar DWI was retrieved from 3 T MRI acquired between maximal resection and radiation in 37 adults with new-onset HGG (25 glioblastoma; 12 anaplastic astrocytoma). ADC maps were produced with the FSL DTIFIT tool (Oxford Centre for Functional MRI). 3 neuroradiologists manually selected regions of interest (ROI) in normal appearing white matter (NAWM) and in non-enhancing tumor (NT) < 2 cm from the margin of residual enhancing tumor or resection cavity. Normalized ADC (nADC) was computed as the ratio of absolute NT ADC to NAWM ADC. Reproducibility of nADC and absolute ADC among the readers' ROI was assessed using intra-class correlation coefficient (ICC) and within-subject coefficient of variation (wCV). Correlations of ADC and nADC with OS were compared using receiver operating characteristics (ROC) analysis. A p value 0.05 was considered statistically significant. Both mean ADC and nADC differed significantly between patients subgrouped by 15-month OS (p = 0.0014 and 0.0073 respectively). wCV and ICC among the readers were similar for absolute and normalized ADC. In ROC analysis of correlation with OS, nADC did not perform significantly better than absolute ADC. Normalization does not significantly improve the correlation of absolute ADC with OS in HGG, suggesting that normalization is not necessary for clinical or research ADC analysis in HGG patients.

Separation of antibody drug conjugate species by RPLC: A generic method development approach.

PubMed

Fekete, Szabolcs; Molnár, Imre; Guillarme, Davy

2017-04-15

This study reports the use of modelling software for the successful method development of IgG1 cysteine conjugated antibody drug conjugate (ADC) in RPLC. The goal of such a method is to be able to calculate the average drug to antibody ratio (DAR) of and ADC product. A generic method development strategy was proposed including the optimization of mobile phase temperature, gradient profile and mobile phase ternary composition. For the first time, a 3D retention modelling was presented for large therapeutic protein. Based on a limited number of preliminary experiments, a fast and efficient separation of the DAR species of a commercial ADC sample, namely brentuximab vedotin, was achieved. The prediction offered by the retention model was found to be highly reliable, with an average error of retention time prediction always lower than 0.5% using a 2D or 3D retention models. For routine purpose, four to six initial experiments were required to build the 2D retention models, while 12 experiments were recommended to create the 3D model. At the end, RPLC can therefore be considered as a good method for estimating the average DAR of an ADC, based on the observed peak area ratios of RPLC chromatogram of the reduced ADC sample. Copyright © 2017 Elsevier B.V. All rights reserved.

Toward uniform implementation of parametric map Digital Imaging and Communication in Medicine standard in multisite quantitative diffusion imaging studies.

PubMed

Malyarenko, Dariya; Fedorov, Andriy; Bell, Laura; Prah, Melissa; Hectors, Stefanie; Arlinghaus, Lori; Muzi, Mark; Solaiyappan, Meiyappan; Jacobs, Michael; Fung, Maggie; Shukla-Dave, Amita; McManus, Kevin; Boss, Michael; Taouli, Bachir; Yankeelov, Thomas E; Quarles, Christopher Chad; Schmainda, Kathleen; Chenevert, Thomas L; Newitt, David C

2018-01-01

This paper reports on results of a multisite collaborative project launched by the MRI subgroup of Quantitative Imaging Network to assess current capability and provide future guidelines for generating a standard parametric diffusion map Digital Imaging and Communication in Medicine (DICOM) in clinical trials that utilize quantitative diffusion-weighted imaging (DWI). Participating sites used a multivendor DWI DICOM dataset of a single phantom to generate parametric maps (PMs) of the apparent diffusion coefficient (ADC) based on two models. The results were evaluated for numerical consistency among models and true phantom ADC values, as well as for consistency of metadata with attributes required by the DICOM standards. This analysis identified missing metadata descriptive of the sources for detected numerical discrepancies among ADC models. Instead of the DICOM PM object, all sites stored ADC maps as DICOM MR objects, generally lacking designated attributes and coded terms for quantitative DWI modeling. Source-image reference, model parameters, ADC units and scale, deemed important for numerical consistency, were either missing or stored using nonstandard conventions. Guided by the identified limitations, the DICOM PM standard has been amended to include coded terms for the relevant diffusion models. Open-source software has been developed to support conversion of site-specific formats into the standard representation.

Quantitative analysis of diffusion tensor imaging (DTI) using statistical parametric mapping (SPM) for brain disorders

NASA Astrophysics Data System (ADS)

Lee, Jae-Seung; Im, In-Chul; Kang, Su-Man; Goo, Eun-Hoe; Kwak, Byung-Joon

2013-07-01

This study aimed to quantitatively analyze data from diffusion tensor imaging (DTI) using statistical parametric mapping (SPM) in patients with brain disorders and to assess its potential utility for analyzing brain function. DTI was obtained by performing 3.0-T magnetic resonance imaging for patients with Alzheimer's disease (AD) and vascular dementia (VD), and the data were analyzed using Matlab-based SPM software. The two-sample t-test was used for error analysis of the location of the activated pixels. We compared regions of white matter where the fractional anisotropy (FA) values were low and the apparent diffusion coefficients (ADCs) were increased. In the AD group, the FA values were low in the right superior temporal gyrus, right inferior temporal gyrus, right sub-lobar insula, and right occipital lingual gyrus whereas the ADCs were significantly increased in the right inferior frontal gyrus and right middle frontal gyrus. In the VD group, the FA values were low in the right superior temporal gyrus, right inferior temporal gyrus, right limbic cingulate gyrus, and right sub-lobar caudate tail whereas the ADCs were significantly increased in the left lateral globus pallidus and left medial globus pallidus. In conclusion by using DTI and SPM analysis, we were able to not only determine the structural state of the regions affected by brain disorders but also quantitatively analyze and assess brain function.

Experimental Setup and Commissioning of a Test Facility for Gain Evaluation of Microchannel-Plate Photomultipliers in High Magnetic Field at Jefferson Lab

NASA Astrophysics Data System (ADS)

Bringley, Eric; Cao, Tongtong; Ilieva, Yordonka; Nadel-Turonski, Pawel; Park, Kijun; Zorn, Carl

2014-09-01

At the Thomas Jefferson National Accelerator Facility (JLab) a research and development project for a Detector of Internally-Reflected Cherenkov light for the upcoming Electron Ion Collider is underway. One goal is the development of a compact readout camera that can operate in high magnetic fields. Small-size photon sensors, such as Microchannel-Plate Photomultipliers (MCP-PMT), are key components of the readout. Here we present our work to set up and commission a dedicated test facility at JLab where MCP-PMT gain is evaluated in magnetic fields of up to 5 T, and to develop a test procedure and analysis software to determine the gain. We operate the setup in a single-photon mode, where a light-emitting diode delivers photons to the sensor's photocathode. The PMT spectrum is measured with a flash Analog-to-Digital converter (fADC). We model the spectrum as a sum of an exponential background and a convolution of Poisson and Gaussian distributions of the pedestal and multiple photoelectron peaks, respectively. We determine the PMT's gain from the position of the single-photoelectron peak obtained by fitting the fADC spectrum to the model. Our gain uncertainty is <10%. The facility is now established and will have a long-lasting value for sensor tests and beyond-nuclear-physics applications.

The Adc/Lmb System Mediates Zinc Acquisition in Streptococcus agalactiae and Contributes to Bacterial Growth and Survival

PubMed Central

Moulin, Pauline; Patron, Kévin; Cano, Camille; Zorgani, Mohamed Amine; Camiade, Emilie; Borezée-Durant, Elise; Rosenau, Agnès; Mereghetti, Laurent

2016-01-01

ABSTRACT The Lmb protein of Streptococcus agalactiae is described as an adhesin that binds laminin, a component of the human extracellular matrix. In this study, we revealed a new role for this protein in zinc uptake. We also identified two Lmb homologs, AdcA and AdcAII, redundant binding proteins that combine with the AdcCB translocon to form a zinc-ABC transporter. Expression of this transporter is controlled by the zinc concentration in the medium through the zinc-dependent regulator AdcR. Triple deletion of lmb, adcA, and adcAII, or that of the adcCB genes, impaired growth and cell separation in a zinc-restricted environment. Moreover, we found that this Adc zinc-ABC transporter promotes S. agalactiae growth and survival in some human biological fluids, suggesting that it contributes to the infection process. These results indicated that zinc has biologically vital functions in S. agalactiae and that, under the conditions tested, the Adc/Lmb transporter constitutes the main zinc acquisition system of the bacterium. IMPORTANCE A zinc transporter, composed of three redundant binding proteins (Lmb, AdcA, and AdcAII), was characterized in Streptococcus agalactiae. This system was shown to be essential for bacterial growth and morphology in zinc-restricted environments, including human biological fluids. PMID:27672194

Whole-lesion apparent diffusion coefficient histogram analysis: significance in T and N staging of gastric cancers.

PubMed

Liu, Song; Zhang, Yujuan; Chen, Ling; Guan, Wenxian; Guan, Yue; Ge, Yun; He, Jian; Zhou, Zhengyang

2017-10-02

Whole-lesion apparent diffusion coefficient (ADC) histogram analysis has been introduced and proved effective in assessment of multiple tumors. However, the application of whole-volume ADC histogram analysis in gastrointestinal tumors has just started and never been reported in T and N staging of gastric cancers. Eighty patients with pathologically confirmed gastric carcinomas underwent diffusion weighted (DW) magnetic resonance imaging before surgery prospectively. Whole-lesion ADC histogram analysis was performed by two radiologists independently. The differences of ADC histogram parameters among different T and N stages were compared with independent-samples Kruskal-Wallis test. Receiver operating characteristic (ROC) analysis was performed to evaluate the performance of ADC histogram parameters in differentiating particular T or N stages of gastric cancers. There were significant differences of all the ADC histogram parameters for gastric cancers at different T (except ADC min and ADC max ) and N (except ADC max ) stages. Most ADC histogram parameters differed significantly between T1 vs T3, T1 vs T4, T2 vs T4, N0 vs N1, N0 vs N3, and some parameters (ADC 5% , ADC 10% , ADC min ) differed significantly between N0 vs N2, N2 vs N3 (all P < 0.05). Most parameters except ADC max performed well in differentiating different T and N stages of gastric cancers. Especially for identifying patients with and without lymph node metastasis, the ADC 10% yielded the largest area under the ROC curve of 0.794 (95% confidence interval, 0.677-0.911). All the parameters except ADC max showed excellent inter-observer agreement with intra-class correlation coefficients higher than 0.800. Whole-volume ADC histogram parameters held great potential in differentiating different T and N stages of gastric cancers preoperatively.

Correlation Between Minimum Apparent Diffusion Coefficient (ADCmin) and Tumor Cellularity: A Meta-analysis.

PubMed

Surov, Alexey; Meyer, Hans Jonas; Wienke, Andreas

2017-07-01

Diffusion-weighted imaging (DWI) is a magnetic resonance imaging (MRI) technique based on measure of water diffusion that can provide information about tissue microstructure, especially about cell count. Increase of cell density induces restriction of water diffusion and decreases apparent diffusion coefficient (ADC). ADC can be divided into three sub-parameters: ADC minimum or ADC min , mean ADC or ADC mean and ADC maximum or ADC max Some studies have suggested that ADC min shows stronger correlations with cell count in comparison to other ADC fractions and may be used as a parameter for estimation of tumor cellularity. The aim of the present meta-analysis was to summarize correlation coefficients between ADC min and cellularity in different tumors based on large patient data. For this analysis, MEDLINE database was screened for associations between ADC and cell count in different tumors up to September 2016. For this work, only data regarding ADC min were included. Overall, 12 publications with 317 patients were identified. Spearman's correlation coefficient was used to analyze associations between ADC min and cellularity. The reported Pearson correlation coefficients in some publications were converted into Spearman correlation coefficients. The pooled correlation coefficient for all included studies was ρ=-0.59 (95% confidence interval (CI)=-0.72 to -0.45), heterogeneity Tau 2 =0.04 (p<0.0001), I 2 =73%, test for overall effect Z=8.67 (p<0.00001). ADC min correlated moderately with tumor cellularity. The calculated correlation coefficient is not stronger in comparison to the reported coefficient for ADC mean and, therefore, ADC min does not represent a better means to reflect cellularity. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Evaluation of the normal-to-diseased apparent diffusion coefficient ratio as an indicator of prostate cancer aggressiveness.

PubMed

Lebovici, Andrei; Sfrangeu, Silviu A; Feier, Diana; Caraiani, Cosmin; Lucan, Ciprian; Suciu, Mihai; Elec, Florin; Iacob, Gheorghita; Buruian, Mircea

2014-05-10

We tested the feasibility of a simple method for assessment of prostate cancer (PCa) aggressiveness using diffusion-weighted magnetic resonance imaging (MRI) to calculate apparent diffusion coefficient (ADC) ratios between prostate cancer and healthy prostatic tissue. The requirement for institutional review board approval was waived. A set of 20 standardized core transperineal saturation biopsy specimens served as the reference standard for placement of regions of interest on ADC maps in tumorous and normal prostatic tissue of 22 men with PCa (median Gleason score: 7; range, 6-9). A total of 128 positive sectors were included for evaluation. Two diagnostic ratios were computed between tumor ADCs and normal sector ADCs: the ADC peripheral ratio (the ratio between tumor ADC and normal peripheral zone tissue, ADC-PR), and the ADC central ratio (the ratio between tumor ADC and normal central zone tissue, ADC-CR). The performance of the two ratios in detecting high-risk tumor foci (Gleason 8 and 9) was assessed using the area under the receiver operating characteristic curve (AUC). Both ADC ratios presented significantly lower values in high-risk tumors (0.48 ± 0.13 for ADC-CR and 0.40 ± 0.09 for ADC-PR) compared with low-risk tumors (0.66 ± 0.17 for ADC-CR and 0.54 ± 0.09 for ADC-PR) (p < 0.001) and had better diagnostic performance (ADC-CR AUC = 0.77, sensitivity = 82.2%, specificity = 66.7% and ADC-PR AUC = 0.90, sensitivity = 93.7%, specificity = 80%) than stand-alone tumor ADCs (AUC of 0.75, sensitivity = 72.7%, specificity = 70.6%) for identifying high-risk lesions. The ADC ratio as an intrapatient-normalized diagnostic tool may be better in detecting high-grade lesions compared with analysis based on tumor ADCs alone, and may reduce the rate of biopsies.

Evaluation of the normal-to-diseased apparent diffusion coefficient ratio as an indicator of prostate cancer aggressiveness

PubMed Central

2014-01-01

Background We tested the feasibility of a simple method for assessment of prostate cancer (PCa) aggressiveness using diffusion-weighted magnetic resonance imaging (MRI) to calculate apparent diffusion coefficient (ADC) ratios between prostate cancer and healthy prostatic tissue. Methods The requirement for institutional review board approval was waived. A set of 20 standardized core transperineal saturation biopsy specimens served as the reference standard for placement of regions of interest on ADC maps in tumorous and normal prostatic tissue of 22 men with PCa (median Gleason score: 7; range, 6–9). A total of 128 positive sectors were included for evaluation. Two diagnostic ratios were computed between tumor ADCs and normal sector ADCs: the ADC peripheral ratio (the ratio between tumor ADC and normal peripheral zone tissue, ADC-PR), and the ADC central ratio (the ratio between tumor ADC and normal central zone tissue, ADC-CR). The performance of the two ratios in detecting high-risk tumor foci (Gleason 8 and 9) was assessed using the area under the receiver operating characteristic curve (AUC). Results Both ADC ratios presented significantly lower values in high-risk tumors (0.48 ± 0.13 for ADC-CR and 0.40 ± 0.09 for ADC-PR) compared with low-risk tumors (0.66 ± 0.17 for ADC-CR and 0.54 ± 0.09 for ADC-PR) (p < 0.001) and had better diagnostic performance (ADC-CR AUC = 0.77, sensitivity = 82.2%, specificity = 66.7% and ADC-PR AUC = 0.90, sensitivity = 93.7%, specificity = 80%) than stand-alone tumor ADCs (AUC of 0.75, sensitivity = 72.7%, specificity = 70.6%) for identifying high-risk lesions. Conclusions The ADC ratio as an intrapatient-normalized diagnostic tool may be better in detecting high-grade lesions compared with analysis based on tumor ADCs alone, and may reduce the rate of biopsies. PMID:24885552

Histogram analysis of apparent diffusion coefficient maps for assessing thymic epithelial tumours: correlation with world health organization classification and clinical staging.

PubMed

Kong, Ling-Yan; Zhang, Wei; Zhou, Yue; Xu, Hai; Shi, Hai-Bin; Feng, Qing; Xu, Xiao-Quan; Yu, Tong-Fu

2018-04-01

To investigate the value of apparent diffusion coefficients (ADCs) histogram analysis for assessing World Health Organization (WHO) pathological classification and Masaoka clinical stages of thymic epithelial tumours. 37 patients with histologically confirmed thymic epithelial tumours were enrolled. ADC measurements were performed using hot-spot ROI (ADC HS-ROI ) and histogram-based approach. ADC histogram parameters included mean ADC (ADC mean ), median ADC (ADC median ), 10 and 90 percentile of ADC (ADC 10 and ADC 90 ), kurtosis and skewness. One-way ANOVA, independent-sample t-test, and receiver operating characteristic were used for statistical analyses. There were significant differences in ADC mean , ADC median , ADC 10 , ADC 90 and ADC HS-ROI among low-risk thymoma (type A, AB, B1; n = 14), high-risk thymoma (type B2, B3; n = 9) and thymic carcinoma (type C, n = 14) groups (all p-values <0.05), while no significant difference in skewness (p = 0.181) and kurtosis (p = 0.088). ADC 10 showed best differentiating ability (cut-off value, ≤0.689 × 10 -3 mm 2 s -1 ; AUC, 0.957; sensitivity, 95.65%; specificity, 92.86%) for discriminating low-risk thymoma from high-risk thymoma and thymic carcinoma. Advanced Masaoka stages (Stage III and IV; n = 24) tumours showed significant lower ADC parameters and higher kurtosis than early Masaoka stage (Stage I and II; n = 13) tumours (all p-values <0.05), while no significant difference on skewness (p = 0.063). ADC 10 showed best differentiating ability (cut-off value, ≤0.689 × 10 -3 mm 2 s -1 ; AUC, 0.913; sensitivity, 91.30%; specificity, 85.71%) for discriminating advanced and early Masaoka stage epithelial tumours. ADC histogram analysis may assist in assessing the WHO pathological classification and Masaoka clinical stages of thymic epithelial tumours. Advances in knowledge: 1. ADC histogram analysis could help to assess WHO pathological classification of thymic epithelial tumours. 2. ADC histogram analysis could help to evaluate Masaoka clinical stages of thymic epithelial tumours. 3. ADC 10 might be a promising imaging biomarker for assessing and characterizing thymic epithelial tumours.

Human papillomavirus prevalence and type‐distribution in cervical glandular neoplasias: Results from a European multinational epidemiological study

PubMed Central

Nowakowski, Andrzej M.; Powell, Ned; McCluggage, W. Glenn; Pirog, Edyta C.; Collas De Souza, Sabrina; Tjalma, Wiebren A.; Rosenlund, Mats; Fiander, Alison; Castro Sánchez, Maria; Damaskou, Vasileia; Joura, Elmar A.; Kirschner, Benny; Koiss, Robert; O'Leary, John; Quint, Wim; Reich, Olaf; Torné, Aureli; Wells, Michael; Rob, Lukas; Kolomiets, Larisa; Molijn, Anco; Savicheva, Alevtina; Shipitsyna, Elena; Rosillon, Dominique; Jenkins, David

2015-01-01

Cervical glandular neoplasias (CGN) present a challenge for cervical cancer prevention due to their complex histopathology and difficulties in detecting preinvasive stages with current screening practices. Reports of human papillomavirus (HPV) prevalence and type‐distribution in CGN vary, providing uncertain evidence to support prophylactic vaccination and HPV screening. This study [108288/108290] assessed HPV prevalence and type‐distribution in women diagnosed with cervical adenocarcinoma in situ (AIS, N = 49), adenosquamous carcinoma (ASC, N = 104), and various adenocarcinoma subtypes (ADC, N = 461) from 17 European countries, using centralised pathology review and sensitive HPV testing. The highest HPV‐positivity rates were observed in AIS (93.9%), ASC (85.6%), and usual‐type ADC (90.4%), with much lower rates in rarer ADC subtypes (clear‐cell: 27.6%; serous: 30.4%; endometrioid: 12.9%; gastric‐type: 0%). The most common HPV types were restricted to HPV16/18/45, accounting for 98.3% of all HPV‐positive ADC. There were variations in HPV prevalence and ADC type‐distribution by country. Age at diagnosis differed by ADC subtype, with usual‐type diagnosed in younger women (median: 43 years) compared to rarer subtypes (medians between 57 and 66 years). Moreover, HPV‐positive ADC cases were younger than HPV‐negative ADC. The six years difference in median age for women with AIS compared to those with usual‐type ADC suggests that cytological screening for AIS may be suboptimal. Since the great majority of CGN are HPV16/18/45‐positive, the incorporation of prophylactic vaccination and HPV testing in cervical cancer screening are important prevention strategies. Our results suggest that special attention should be given to certain rarer ADC subtypes as most appear to be unrelated to HPV. PMID:26096203

Characterization of diffuse orbital mass using Apparent diffusion coefficient in 3-tesla MRI.

PubMed

ElKhamary, Sahar M; Galindo-Ferreiro, Alicia; AlGhafri, Laila; Khandekar, Rajiv; Schellini, Silvana Artioli

2018-01-01

To evaluate if the apparent diffusion coefficient (ADC) value in diffusion-weighted magnetic resonance imaging (DW-MRI) improves the diagnostic accuracy of diffuse orbital masses. ADC DW-MRI was used to evaluate cases of diffuse orbital masses at our institution from 2000 to 2015. Lesions were grouped according to histopathologic diagnosis as, benign, pre-malignant and malignant. Lymphoproliferative lesions were further subgrouped as lymphoma or other lymphoproliferative lesions. The validity of the ADC value for the diffuse orbital mass was compared between groups. The area under curve (AUC) was also calculated. Thirty-nine cases of diffuse orbital masses were evaluated. The median ADC was 0.58 (25% quartile 0.48; minimum: 0.45; maximum: 1.72 × 10 (-3) ) for the malignant tumors and 1.19 (25% quartile 0.7; minimum: 0.5; maximum: 1.95 × 10 (-3)  mm (2)  s (-1) ) for benign lesions. This difference in ADC between lesions was statistically significant (Mann Whitney U test P < 0.001). The median ADC was 0.51 (25% quartile 0.48) for lymphomas and 0.9 (25% quartile 0.7) for other lymphoproliferative lesions. This difference in ADC was statistically significant (Mann Whitney U test P = 0.02). An ADC value of 0.8 × 10 (-3)  mm (2)  s (-1) was noted as the ideal threshold value for differentiating malignant from benign diffuse orbital masses. The validity of ADC in predicting a malignant or benign diffuse orbital mass had a sensitivity of 87%, specificity of 67% and accuracy of 88%. ADC is a promising imaging metric to characterize malignant and benign diffuse orbital masses and to distinguish lymphomas from other non-lymphoproliferative lesions.

The Adc/Lmb System Mediates Zinc Acquisition in Streptococcus agalactiae and Contributes to Bacterial Growth and Survival.

PubMed

Moulin, Pauline; Patron, Kévin; Cano, Camille; Zorgani, Mohamed Amine; Camiade, Emilie; Borezée-Durant, Elise; Rosenau, Agnès; Mereghetti, Laurent; Hiron, Aurélia

2016-12-15

The Lmb protein of Streptococcus agalactiae is described as an adhesin that binds laminin, a component of the human extracellular matrix. In this study, we revealed a new role for this protein in zinc uptake. We also identified two Lmb homologs, AdcA and AdcAII, redundant binding proteins that combine with the AdcCB translocon to form a zinc-ABC transporter. Expression of this transporter is controlled by the zinc concentration in the medium through the zinc-dependent regulator AdcR. Triple deletion of lmb, adcA, and adcAII, or that of the adcCB genes, impaired growth and cell separation in a zinc-restricted environment. Moreover, we found that this Adc zinc-ABC transporter promotes S. agalactiae growth and survival in some human biological fluids, suggesting that it contributes to the infection process. These results indicated that zinc has biologically vital functions in S. agalactiae and that, under the conditions tested, the Adc/Lmb transporter constitutes the main zinc acquisition system of the bacterium. A zinc transporter, composed of three redundant binding proteins (Lmb, AdcA, and AdcAII), was characterized in Streptococcus agalactiae This system was shown to be essential for bacterial growth and morphology in zinc-restricted environments, including human biological fluids. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Prediction of non-linear pharmacokinetics in humans of an antibody-drug conjugate (ADC) when evaluation of higher doses in animals is limited by tolerability: Case study with an anti-CD33 ADC.

PubMed

Figueroa, Isabel; Leipold, Doug; Leong, Steve; Zheng, Bing; Triguero-Carrasco, Montserrat; Fourie-O'Donohue, Aimee; Kozak, Katherine R; Xu, Keyang; Schutten, Melissa; Wang, Hong; Polson, Andrew G; Kamath, Amrita V

2018-05-14

For antibody-drug conjugates (ADCs) that carry a cytotoxic drug, doses that can be administered in preclinical studies are typically limited by tolerability, leading to a narrow dose range that can be tested. For molecules with non-linear pharmacokinetics (PK), this limited dose range may be insufficient to fully characterize the PK of the ADC and limits translation to humans. Mathematical PK models are frequently used for molecule selection during preclinical drug development and for translational predictions to guide clinical study design. Here, we present a practical approach that uses limited PK and receptor occupancy (RO) data of the corresponding unconjugated antibody to predict ADC PK when conjugation does not alter the non-specific clearance or the antibody-target interaction. We used a 2-compartment model incorporating non-specific and specific (target mediated) clearances, where the latter is a function of RO, to describe the PK of anti-CD33 ADC with dose-limiting neutropenia in cynomolgus monkeys. We tested our model by comparing PK predictions based on the unconjugated antibody to observed ADC PK data that was not utilized for model development. Prospective prediction of human PK was performed by incorporating in vitro binding affinity differences between species for varying levels of CD33 target expression. Additionally, this approach was used to predict human PK of other previously tested anti-CD33 molecules with published clinical data. The findings showed that, for a cytotoxic ADC with non-linear PK and limited preclinical PK data, incorporating RO in the PK model and using data from the corresponding unconjugated antibody at higher doses allowed the identification of parameters to characterize monkey PK and enabled human PK predictions.

Tensile Properties and Fracture Behavior of Aluminum Alloy Foam Fabricated from Die Castings without Using Blowing Agent by Friction Stir Processing Route

PubMed Central

Hangai, Yoshihiko; Kamada, Hiroto; Utsunomiya, Takao; Kitahara, Soichiro; Kuwazuru, Osamu; Yoshikawa, Nobuhiro

2014-01-01

Al foam has been used in a wide range of applications owing to its light weight, high energy absorption and high sound insulation. One of the promising processes for fabricating Al foam involves the use of a foamable precursor. In this study, ADC12 Al foams with porosities of 67%–78% were fabricated from Al alloy die castings without using a blowing agent by the friction stir processing route. The pore structure and tensile properties of the ADC12 foams were investigated and compared with those of commercially available ALPORAS. From X-ray computed tomography (X-ray CT) observations of the pore structure of ADC12 foams, it was found that they have smaller pores with a narrower distribution than those in ALPORAS. Tensile tests on the ADC12 foams indicated that as their porosity increased, the tensile strength and tensile strain decreased, with strong relation between the porosity, tensile strength, and tensile strain. ADC12 foams exhibited brittle fracture, whereas ALPORAS exhibited ductile fracture, which is due to the nature of the Al alloy used as the base material of the foams. By image-based finite element (FE) analysis using X-ray CT images corresponding to the tensile tests on ADC12 foams, it was shown that the fracture path of ADC12 foams observed in tensile tests and the regions of high stress obtained from FE analysis correspond to each other. Therefore, it is considered that the fracture behavior of ADC12 foams in relation to their pore structure distribution can be investigated by image-based FE analysis. PMID:28788573

Tensile Properties and Fracture Behavior of Aluminum Alloy Foam Fabricated from Die Castings without Using Blowing Agent by Friction Stir Processing Route.

PubMed

Hangai, Yoshihiko; Kamada, Hiroto; Utsunomiya, Takao; Kitahara, Soichiro; Kuwazuru, Osamu; Yoshikawa, Nobuhiro

2014-03-21

Al foam has been used in a wide range of applications owing to its light weight, high energy absorption and high sound insulation. One of the promising processes for fabricating Al foam involves the use of a foamable precursor. In this study, ADC12 Al foams with porosities of 67%-78% were fabricated from Al alloy die castings without using a blowing agent by the friction stir processing route. The pore structure and tensile properties of the ADC12 foams were investigated and compared with those of commercially available ALPORAS. From X-ray computed tomography (X-ray CT) observations of the pore structure of ADC12 foams, it was found that they have smaller pores with a narrower distribution than those in ALPORAS. Tensile tests on the ADC12 foams indicated that as their porosity increased, the tensile strength and tensile strain decreased, with strong relation between the porosity, tensile strength, and tensile strain. ADC12 foams exhibited brittle fracture, whereas ALPORAS exhibited ductile fracture, which is due to the nature of the Al alloy used as the base material of the foams. By image-based finite element (FE) analysis using X-ray CT images corresponding to the tensile tests on ADC12 foams, it was shown that the fracture path of ADC12 foams observed in tensile tests and the regions of high stress obtained from FE analysis correspond to each other. Therefore, it is considered that the fracture behavior of ADC12 foams in relation to their pore structure distribution can be investigated by image-based FE analysis.

Synergistic co-targeting of prostate-specific membrane antigen and androgen receptor in prostate cancer.

PubMed

Murga, Jose D; Moorji, Sameer M; Han, Amy Q; Magargal, Wells W; DiPippo, Vincent A; Olson, William C

2015-02-15

Antibody-drug conjugates (ADCs) are an emerging class of cancer therapies that have demonstrated favorable activity both as single agents and as components of combination regimens. Phase 2 testing of an ADC targeting prostate-specific membrane antigen (PSMA) in advanced prostate cancer has shown antitumor activity. The present study examined PSMA ADC used in combination with potent antiandrogens (enzalutamide and abiraterone) and other compounds. Antiproliferative activity and expression of PSMA, prostate-specific antigen and androgen receptor were evaluated in the prostate cancer cell lines LNCaP and C4-2. Cells were tested for susceptibility to antiandrogens or other inhibitors, used alone and in combination with PSMA ADC. Potential drug synergy or antagonism was evaluated using the Bliss independence method. Enzalutamide and abiraterone demonstrated robust, statistically significant synergy when combined with PSMA ADC. Largely additive activity was observed between the antiandrogens and the individual components of the ADC (free drug and unmodified antibody). Rapamycin also synergized with PSMA ADC in certain settings. Synergy was linked in part to upregulation of PSMA expression. In androgen-dependent LNCaP cells, enzalutamide and abiraterone each inhibited proliferation, upregulated PSMA expression, and synergized with PSMA ADC. In androgen-independent C4-2 cells, enzalutamide and abiraterone showed no measurable antiproliferative activity on their own but increased PSMA expression and synergized with PSMA ADC nonetheless. PSMA expression increased progressively over 3 weeks with enzalutamide and returned to baseline levels 1 week after enzalutamide removal. The findings support exploration of clinical treatment regimens that combine potent antiandrogens and PSMA-targeted therapies for prostate cancer. © 2014 Wiley Periodicals, Inc.

XML at the ADC: Steps to a Next Generation Data Archive

NASA Astrophysics Data System (ADS)

Shaya, E.; Blackwell, J.; Gass, J.; Oliversen, N.; Schneider, G.; Thomas, B.; Cheung, C.; White, R. A.

1999-05-01

The eXtensible Markup Language (XML) is a document markup language that allows users to specify their own tags, to create hierarchical structures to qualify their data, and to support automatic checking of documents for structural validity. It is being intensively supported by nearly every major corporate software developer. Under the funds of a NASA AISRP proposal, the Astronomical Data Center (ADC, http://adc.gsfc.nasa.gov) is developing an infrastructure for importation, enhancement, and distribution of data and metadata using XML as the document markup language. We discuss the preliminary Document Type Definition (DTD, at http://adc.gsfc.nasa.gov/xml) which specifies the elements and their attributes in our metadata documents. This attempts to define both the metadata of an astronomical catalog and the `header' information of an astronomical table. In addition, we give an overview of the planned flow of data through automated pipelines from authors and journal presses into our XML archive and retrieval through the web via the XML-QL Query Language and eXtensible Style Language (XSL) scripts. When completed, the catalogs and journal tables at the ADC will be tightly hyperlinked to enhance data discovery. In addition one will be able to search on fragmentary information. For instance, one could query for a table by entering that the second author is so-and-so or that the third author is at such-and-such institution.

Correlation of apparent diffusion coefficient ratio on 3.0 T MRI with prostate cancer Gleason score.

PubMed

Jyoti, Rajeev; Jain, Tarun Pankaj; Haxhimolla, Hodo; Liddell, Heath; Barrett, Sean Edward

2018-01-01

The purpose was to investigate the usefulness of ADC ratio on Diffusion MRI to discriminate between benign and malignant lesions of Prostate. Images of patients who underwent in-gantry MRI guided prostate lesion biopsy were retrospectively analyzed. Prostate Cancers with 20% or more Gleason score (GS) pattern 3 + 3 = 6 in each core or any volume of higher Gleason score pattern were included. ADC ratio was calculated by two reviewers for each lesion. The ADC ratio was calculated for each lesion by dividing the lowest ADC value in a lesion and highest ADC value in normal prostate in peripheral zone (PZ). ADC ratio values were compared with the biopsy result. Data was analysed using independent samples T-test, Spearman correlation, intra-class correlation coefficient (ICC) and Receiver operating characteristic (ROC) curve. 45 lesions in 33 patients were analyzed. 12 lesions were in transitional zone (TZ) and 33 in perpheral zone PZ. All lesions demonstrated an ADC ratio of 0.45 or lower. GS demonstrated a negative correlation with both the ADC value and ADC ratio . However, ADC ratio (p < 0.001) demonstrated a stronger correlation compared to ADC value alone (p = 0.014). There was no significant statistical difference between GS 3 + 4 and GS 4 + 3 mean ADC tumour value (p = 0.167). However when using ADC ratio , there was a significant difference (p = 0.032). ROC curve analysis demonstrated an area under the curve of 0.83 using ADC ratio and 0.76 when using ADC tumour value when discriminating Gleason 6 from Gleason ≥7 tumours. Inter-observer reliability in the calculation of ADC ratios was excellent, with ICC of 0.964. ADC ratio is a reliable and reproducible tool in quantification of diffusion restriction for clinically significant prostate cancer foci.

Apparent diffusion coefficient measurement in glioma: Influence of region-of-interest determination methods on apparent diffusion coefficient values, interobserver variability, time efficiency, and diagnostic ability.

PubMed

Han, Xu; Suo, Shiteng; Sun, Yawen; Zu, Jinyan; Qu, Jianxun; Zhou, Yan; Chen, Zengai; Xu, Jianrong

2017-03-01

To compare four methods of region-of-interest (ROI) placement for apparent diffusion coefficient (ADC) measurements in distinguishing low-grade gliomas (LGGs) from high-grade gliomas (HGGs). Two independent readers measured ADC parameters using four ROI methods (single-slice [single-round, five-round and freehand] and whole-volume) on 43 patients (20 LGGs, 23 HGGs) who had undergone 3.0 Tesla diffusion-weighted imaging and time required for each method of ADC measurements was recorded. Intraclass correlation coefficients (ICCs) were used to assess interobserver variability of ADC measurements. Mean and minimum ADC values and time required were compared using paired Student's t-tests. All ADC parameters (mean/minimum ADC values of three single-slice methods, mean/minimum/standard deviation/skewness/kurtosis/the10 th and 25 th percentiles/median/maximum of whole-volume method) were correlated with tumor grade (low versus high) by unpaired Student's t-tests. Discriminative ability was determined by receiver operating characteristic curves. All ADC measurements except minimum, skewness, and kurtosis of whole-volume ROI differed significantly between LGGs and HGGs (all P < 0.05). Mean ADC value of single-round ROI had the highest effect size (0.72) and the greatest areas under the curve (0.872). Three single-slice methods had good to excellent ICCs (0.67-0.89) and the whole-volume method fair to excellent ICCs (0.32-0.96). Minimum ADC values differed significantly between whole-volume and single-round ROI (P = 0.003) and, between whole-volume and five-round ROI (P = 0.001). The whole-volume method took significantly longer than all single-slice methods (all P < 0.001). ADC measurements are influenced by ROI determination methods. Whole-volume histogram analysis did not yield better results than single-slice methods and took longer. Mean ADC value derived from single-round ROI is the most optimal parameter for differentiating LGGs from HGGs. 3 J. Magn. Reson. Imaging 2017;45:722-730. © 2016 International Society for Magnetic Resonance in Medicine.

Apparent diffusion coefficient is highly reproducible on preclinical imaging systems: Evidence from a seven-center multivendor study.

PubMed

Doblas, Sabrina; Almeida, Gilberto S; Blé, François-Xavier; Garteiser, Philippe; Hoff, Benjamin A; McIntyre, Dominick J O; Wachsmuth, Lydia; Chenevert, Thomas L; Faber, Cornelius; Griffiths, John R; Jacobs, Andreas H; Morris, David M; O'Connor, James P B; Robinson, Simon P; Van Beers, Bernard E; Waterton, John C

2015-12-01

To evaluate between-site agreement of apparent diffusion coefficient (ADC) measurements in preclinical magnetic resonance imaging (MRI) systems. A miniaturized thermally stable ice-water phantom was devised. ADC (mean and interquartile range) was measured over several days, on 4.7T, 7T, and 9.4T Bruker, Agilent, and Magnex small-animal MRI systems using a common protocol across seven sites. Day-to-day repeatability was expressed as percent variation of mean ADC between acquisitions. Cross-site reproducibility was expressed as 1.96 × standard deviation of percent deviation of ADC values. ADC measurements were equivalent across all seven sites with a cross-site ADC reproducibility of 6.3%. Mean day-to-day repeatability of ADC measurements was 2.3%, and no site was identified as presenting different measurements than others (analysis of variance [ANOVA] P = 0.02, post-hoc test n.s.). Between-slice ADC variability was negligible and similar between sites (P = 0.15). Mean within-region-of-interest ADC variability was 5.5%, with one site presenting a significantly greater variation than the others (P = 0.0013). Absolute ADC values in preclinical studies are comparable between sites and equipment, provided standardized protocols are employed. © 2015 Wiley Periodicals, Inc.

Impact of post-processing methods on apparent diffusion coefficient values.

PubMed

Zeilinger, Martin Georg; Lell, Michael; Baltzer, Pascal Andreas Thomas; Dörfler, Arnd; Uder, Michael; Dietzel, Matthias

2017-03-01

The apparent diffusion coefficient (ADC) is increasingly used as a quantitative biomarker in oncological imaging. ADC calculation is based on raw diffusion-weighted imaging (DWI) data, and multiple post-processing methods (PPMs) have been proposed for this purpose. We investigated whether PPM has an impact on final ADC values. Sixty-five lesions scanned with a standardized whole-body DWI-protocol at 3 T served as input data (EPI-DWI, b-values: 50, 400 and 800 s/mm 2 ). Using exactly the same ROI coordinates, four different PPM (ADC_1-ADC_4) were executed to calculate corresponding ADC values, given as [10 -3 mm 2 /s] of each lesion. Statistical analysis was performed to intra-individually compare ADC values stratified by PPM (Wilcoxon signed-rank tests: α = 1 %; descriptive statistics; relative difference/∆; coefficient of variation/CV). Stratified by PPM, mean ADCs ranged from 1.136-1.206 *10 -3 mm 2 /s (∆ = 7.0 %). Variances between PPM were pronounced in the upper range of ADC values (maximum: 2.540-2.763 10 -3 mm 2 /s, ∆ = 8 %). Pairwise comparisons identified significant differences between all PPM (P ≤ 0.003; mean CV = 7.2 %) and reached 0.137 *10 -3 mm 2 /s within the 25th-75th percentile. Altering the PPM had a significant impact on the ADC value. This should be considered if ADC values from different post-processing methods are compared in patient studies. • Post-processing methods significantly influenced ADC values. • The mean coefficient of ADC variation due to PPM was 7.2 %. • To achieve reproducible ADC values, standardization of post-processing is recommended.

Investigation of aquaporins and apparent diffusion coefficient from ultra-high b-values in a rat model of diabetic nephropathy.

PubMed

Wang, Yu; Zhang, Heng; Zhang, Ruzhi; Zhao, Zhoushe; Xu, Ziqian; Wang, Lei; Liu, Rongbo; Gao, Fabao

2017-01-01

To assess kidney damage in a rat model of type-2 diabetic nephropathy based on apparent diffusion coefficient (ADC) data obtained from ultra-high b-values and discuss its relationship to the expression of aquaporins (AQPs). This study was approved by the institutional Animal Care and Use Committee. Thirty male Sprague-Dawley rats were randomised into two groups: (1) untreated controls and (2) diabetes mellitus (DM). All rats underwent diffusion-weighted imaging (DWI) with 18 b-values (0-4500 s/mm 2 ). Maps of low ADC (ADC low ), standard ADC (ADC st ) and ultra-high ADC (ADC uh ) were calculated from low b-values (0-200 s/mm 2 ), standard b-values (300-1500 s/mm 2 ) and ultra-high b-values (1700-4500 s/mm 2 ), respectively. The expression of AQPs in the kidneys was studied using immunohistochemistry. Laboratory parameters of diabetic and kidney functions, ADC low , ADC st , ADC uh , and the optical density (OD) of AQP expression in the two groups were compared using an independent t test. Correlations between ADCs and the OD of AQP expression were evaluated by Pearson's correlation analysis. ADC uh were significantly higher in the cortex (CO), outer stripe of the outer medulla (OS) and inner stripe of the outer medulla (IS), and the OD values of AQ-2 were significantly higher in the OS, IS and inner medulla (IM) in DM animals compared with control animals. ADC uh and OD values of AQP-2 expression were positively correlated in the OS, IS and IM of the kidney. ADC uh may work as useful metrics for early detection of kidney damage in diabetic nephropathy and may be associated with AQP-2 expression.

Current Status of the Beam Position Monitoring System at TLS

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

Kuo, C. H.; Hu, K. H.; Chen, Jenny

2006-11-20

The beam position monitoring system is an important part of a synchrotron light source that supports its routine operation and studies of beam physics. The Taiwan light source is equipped with 59 BPMs. Highly precise closed orbits are measured by multiplexing BPMs. Data are acquired using multi-channel 16-bit ADC modules. Orbit data are sampled every millisecond. Fast orbit data are shared in a reflective memory network to support fast orbit feedback. Averaged data were updated to control database at a rate of 10 Hz. A few new generation digital BPMs were tested to evaluate their performance and functionality. This reportmore » summarizes the system structure, the software environment and the preliminary beam test of the BPM system.« less

Current Status of the Beam Position Monitoring System at TLS

NASA Astrophysics Data System (ADS)

Kuo, C. H.; Hu, K. H.; Chen, Jenny; Lee, Demi; Wang, C. J.; Hsu, S. Y.; Hsu, K. T.

2006-11-01

The beam position monitoring system is an important part of a synchrotron light source that supports its routine operation and studies of beam physics. The Taiwan light source is equipped with 59 BPMs. Highly precise closed orbits are measured by multiplexing BPMs. Data are acquired using multi-channel 16-bit ADC modules. Orbit data are sampled every millisecond. Fast orbit data are shared in a reflective memory network to support fast orbit feedback. Averaged data were updated to control database at a rate of 10 Hz. A few new generation digital BPMs were tested to evaluate their performance and functionality. This report summarizes the system structure, the software environment and the preliminary beam test of the BPM system.

Value of apparent diffusion coefficient (ADC) in assessing radiotherapy and chemotherapy success in cervical cancer.

PubMed

Fu, Zhan-Zhao; Peng, Yong; Cao, Li-Yan; Chen, Yan-Sheng; Li, Kun; Fu, Bao-Hong

2015-06-01

We investigated the clinical significance of apparent diffusion coefficient (ADC) values in diffusion-weighted magnetic resonance imaging (DWI) in monitoring the efficacy of radiotherapy (RT) and chemotherapy (CT) treatments in cervical cancer. In order to identify relevant high quality clinical cohort studies reporting the use of DWI in cervical cancers, the following electronic databases in English and Chinese languages were comprehensively searched: MEDLINE, Science Citation Index database, Cochrane Library Database, PubMed, Embase, CINAHL, and Current Contents Index; Chinese Biomedical Database, Chinese Journal Full-Text Database. All selected studies were published prior to March 2014, and data extracted from these studies were analyzed using STATA 12.0 statistical software. We initially retrieved 196 articles (79 Chinese articles and 117 English articles) through database searches and finally selected sixteen cohort studies for this meta-analysis. The 16 studies contained a combined total of 517 subjects, and all selected studies reported the mean ADC value (10(-3) mm(2)/s) in DWI in cervical cancer patients treated with RT and CT. Combined standardized mean difference (SMD) suggested that the mean post-RT and mean post-CT ADC values were significantly higher than the mean pre-RT and mean pre-CT ADC values, respectively, in cervical cancer patients (SMD=2.95, 95% CI=2.19-3.72, P<0.001). Ethnicity-stratified analysis revealed that increased ADC values were observed post-RT and post-CT in both Caucasian (SMD=1.44, 95% CI=0.93-1.95, P<0.001) and Asian populations (SMD=3.32, 95% CI=2.42-4.22, P<0.001), compared with the mean ADC values before RT and CT, respectively, in the two subgroups. Further, subgroup analysis based on b-value revealed that higher ADC values were found in cervical cancer patients after RT and CT, compared to before RT and CT treatment, with both b value≤900 (SMD=3.71, 95% CI=2.35-5.07, P<0.001) and >900 (SMD=2.55, 95% CI=1.78-3.32, P<0.001). The mean ADC value in patients without residual tumor post-RT and post-CT treatment was significantly higher than seen in patients with residual tumors (SMD=0.80, 95% CI=0.49-1.12, P<0.001). Our meta-analysis revealed a significant correlation between mean ADC values and the clinical response to RT and CT treatment. Thus, ADC values in DWI may be effective in evaluating the clinical outcome of treatments in cervical cancer patients. Copyright © 2015 Elsevier Inc. All rights reserved.

Apparent diffusion coefficient on magnetic resonance imaging (MRI) in bladder cancer: relations with recurrence/progression risk

PubMed Central

Kikuchi, Ken; Shigihara, Takeshi; Hashimoto, Yuko; Miyajima, Masayuki; Haga, Nobuhiro; Kojima, Yoshiyuki; Shishido, Fumio

2017-01-01

Abstract AIMS: To evaluate the relationship between the apparent diffusion coefficient (ADC) value for bladder cancer and the recurrence/progression risk of post-transurethral resection (TUR). METHODS: Forty-one patients with initial and non-muscle-invasive bladder cancer underwent MRI from 2009 to 2012. Two radiologists measured ADC values. A pathologist calculated the recurrence/progression scores, and risk was classified based on the scores. Pearson’s correlation was used to analyze the correlations of ADC value with each score and with each risk group, and the optimal cut-off value was established based on receiver operating characteristic (ROC) curve analysis. Furthermore, the relationship between actual recurrence / progression of cases and ADC values was examined by Unpaird U test. RESULTS: There were significant correlations between ADC value and the recurrence score as well as the progression score (P<0.01, P<0.01, respectively). There were also significant correlations between ADC value and the recurrence risk group as well as progression risk group (P=0.042, P<0.01, respectively). The ADC cut-off value on ROC analysis was 1.365 (sensitivity 100%; specificity 97.4%) for the low and intermediate recurrence risk groups, 1.024 (sensitivity 47.4%; specificity 100%) for the intermediate and high recurrence risk groups, 1.252 (sensitivity 83.3%; specificity 81.3%) for the low and intermediate progression risk groups, and 0.955 (sensitivity 87.5%; specificity 63.2%) between the intermediate and high progression risk groups. The difference between the ADC values of the recurrence and nonrecurrence group in Unpaired t test was significant (P<0.05). CONCLUSION: ADC on MRI in bladder cancer could potentially be useful, non-invasive measurement for estimating the risks of recurrence and progression. PMID:28680010

ADC histogram analysis for adrenal tumor histogram analysis of apparent diffusion coefficient in differentiating adrenal adenoma from pheochromocytoma.

PubMed

Umanodan, Tomokazu; Fukukura, Yoshihiko; Kumagae, Yuichi; Shindo, Toshikazu; Nakajo, Masatoyo; Takumi, Koji; Nakajo, Masanori; Hakamada, Hiroto; Umanodan, Aya; Yoshiura, Takashi

2017-04-01

To determine the diagnostic performance of apparent diffusion coefficient (ADC) histogram analysis in diffusion-weighted (DW) magnetic resonance imaging (MRI) for differentiating adrenal adenoma from pheochromocytoma. We retrospectively evaluated 52 adrenal tumors (39 adenomas and 13 pheochromocytomas) in 47 patients (21 men, 26 women; mean age, 59.3 years; range, 16-86 years) who underwent DW 3.0T MRI. Histogram parameters of ADC (b-values of 0 and 200 [ADC 200 ], 0 and 400 [ADC 400 ], and 0 and 800 s/mm 2 [ADC 800 ])-mean, variance, coefficient of variation (CV), kurtosis, skewness, and entropy-were compared between adrenal adenomas and pheochromocytomas, using the Mann-Whitney U-test. Receiver operating characteristic (ROC) curves for the histogram parameters were generated to differentiate adrenal adenomas from pheochromocytomas. Sensitivity and specificity were calculated by using a threshold criterion that would maximize the average of sensitivity and specificity. Variance and CV of ADC 800 were significantly higher in pheochromocytomas than in adrenal adenomas (P < 0.001 and P = 0.001, respectively). With all b-value combinations, the entropy of ADC was significantly higher in pheochromocytomas than in adrenal adenomas (all P ≤ 0.001), and showed the highest area under the ROC curve among the ADC histogram parameters for diagnosing adrenal adenomas (ADC 200 , 0.82; ADC 400 , 0.87; and ADC 800 , 0.92), with sensitivity of 84.6% and specificity of 84.6% (cutoff, ≤2.82) with ADC 200 ; sensitivity of 89.7% and specificity of 84.6% (cutoff, ≤2.77) with ADC 400 ; and sensitivity of 94.9% and specificity of 92.3% (cutoff, ≤2.67) with ADC 800 . ADC histogram analysis of DW MRI can help differentiate adrenal adenoma from pheochromocytoma. 3 J. Magn. Reson. Imaging 2017;45:1195-1203. © 2016 International Society for Magnetic Resonance in Medicine.

Common pediatric cerebellar tumors: correlation between cell densities and apparent diffusion coefficient metrics.

PubMed

Koral, Korgün; Mathis, Derek; Gimi, Barjor; Gargan, Lynn; Weprin, Bradley; Bowers, Daniel C; Margraf, Linda

2013-08-01

To test whether there is correlation between cell densities and apparent diffusion coefficient (ADC) metrics of common pediatric cerebellar tumors. This study was reviewed for issues of patient safety and confidentiality and was approved by the Institutional Review Board of the University of Texas Southwestern Medical Center and was compliant with HIPAA. The need for informed consent was waived. Ninety-five patients who had preoperative magnetic resonance imaging and surgical pathologic findings available between January 2003 and June 2011 were included. There were 37 pilocytic astrocytomas, 34 medulloblastomas (23 classic, eight desmoplastic-nodular, two large cell, one anaplastic), 17 ependymomas (13 World Health Organization [WHO] grade II, four WHO grade III), and seven atypical teratoid rhabdoid tumors. ADCs of solid tumor components and normal cerebellum were measured. Tumor-to-normal brain ADC ratios (hereafter, ADC ratio) were calculated. The medulloblastomas and ependymomas were subcategorized according to the latest WHO classification, and tumor cellularity was calculated. Correlation was sought between cell densities and mean tumor ADCs, minimum tumor ADCs, and ADC ratio. When all tumors were considered together, negative correlation was found between cellularity and mean tumor ADCs (ρ = -0.737, P < .05) and minimum tumor ADCs (ρ = -0.736, P < .05) of common pediatric cerebellar tumors. There was no correlation between cellularity and ADC ratio. Negative correlation was found between cellularity and minimum tumor ADC in atypical teratoid rhabdoid tumors (ρ = -0.786, P < .05). In atypical teratoid rhabdoid tumors, no correlation was found between cellularity and mean tumor ADC and ADC ratio. There was no correlation between the ADC metrics and cellularity of the pilocytic astrocytomas, medulloblastomas, and ependymomas. Negative correlation was found between cellularity and ADC metrics of common pediatric cerebellar tumors. Although ADC metrics are useful in the preoperative diagnosis of common pediatric cerebellar tumors and this utility is generally attributed to differences in cellularity of tumors, tumor cellularity may not be the sole determinant of the differences in diffusivity.

A standardized way to select, evaluate, and test an analog-to-digital converter for ultrawide bandwidth radiofrequency signals based on user's needs, ideal, published,and actual specifications

NASA Astrophysics Data System (ADS)

Chang, Daniel Y.; Rowe, Neil C.

2012-06-01

The most important adverse impact on the Electronic Warfare (EW) simulation is that the number of signal sources that can be tested simultaneously is relatively small. When the number of signal sources increases, the analog hardware, complexity and costs grow by the order of N2, since the number of connections among N components is O(N*N) and the signal communication is bi-directional. To solve this problem, digitization of the signal is suggested. In digitizing a radiofrequency signal, an Analog-to-Digital Converter (ADC) is widely used. Most research studies on ADCs are conducted from designer/test engineers' perspective. Some research studies are conducted from market's perspective. This paper presents a generic way to select, evaluate and test ultra high bandwidth COTS ADCs and generate requirements for digitizing continuous time signals from the perspective of user's needs. Based on user's needs, as well as vendor's published, ideal and actual specifications, a decision can be made in selecting a proper ADC for an application. To support our arguments and illustrate the methodology, we evaluate a Tektronix TADC-1000, an 8-bit and 12 gigasamples per second ADC. This project is funded by JEWEL lab, NAWCWD at Point Mugu, CA.

Enhancing Observability of Signal Composition and Error Signatures During Dynamic SEE Analog to Digital Device Testing

NASA Technical Reports Server (NTRS)

Berg, M.; Buchner, S.; Kim, H.; Friendlich, M.; Perez, C.; Phan, A.; Seidleck, C.; LaBel, K.; Kruckmeyer, K.

2010-01-01

A novel approach to dynamic SEE ADC testing is presented. The benefits of this test scheme versus prior implemented techniques include the ability to observe ADC SEE errors that are in the form of phase shifts, single bit upsets, bursts of disrupted signal composition, and device clock loss.

Whole-Lesion Histogram Analysis of Apparent Diffusion Coefficient for the Assessment of Cervical Cancer.

PubMed

Guan, Yue; Shi, Hua; Chen, Ying; Liu, Song; Li, Weifeng; Jiang, Zhuoran; Wang, Huanhuan; He, Jian; Zhou, Zhengyang; Ge, Yun

2016-01-01

The aim of this study was to explore the application of whole-lesion histogram analysis of apparent diffusion coefficient (ADC) values of cervical cancer. A total of 54 women (mean age, 53 years) with cervical cancers underwent 3-T diffusion-weighted imaging with b values of 0 and 800 s/mm prospectively. Whole-lesion histogram analysis of ADC values was performed. Paired sample t test was used to compare differences in ADC histogram parameters between cervical cancers and normal cervical tissues. Receiver operating characteristic curves were constructed to identify the optimal threshold of each parameter. All histogram parameters in this study including ADCmean, ADCmin, ADC10%-ADC90%, mode, skewness, and kurtosis of cervical cancers were significantly lower than those of normal cervical tissues (all P < 0.0001). ADC90% had the largest area under receiver operating characteristic curve of 0.996. Whole-lesion histogram analysis of ADC maps is useful in the assessment of cervical cancer.

uSOP: A Microprocessor-Based Service-Oriented Platform for Control and Monitoring

NASA Astrophysics Data System (ADS)

Aloisio, Alberto; Ameli, Fabrizio; Anastasio, Antonio; Branchini, Paolo; Di Capua, Francesco; Giordano, Raffaele; Izzo, Vincenzo; Tortone, Gennaro

2017-06-01

uSOP is a general purpose single-board computer designed for deep embedded applications in control and monitoring of detectors, sensors, and complex laboratory equipment. In this paper, we present and discuss the main aspects of the hardware and software designs and the expandable peripheral architecture built around serial busses. We show the tests done with state-of-the-art ΔΣ 24-b ADC acquisition modules, in order to assess the achievable noise floor in a typical application. Eventually, we report on the deployment of uSOP in the monitoring system framework of the Belle2 experiment, presently under construction at the KEK Laboratory (Tsukuba, Japan).

Idiopathic normal-pressure hydrocephalus: temporal changes in ADC during cardiac cycle.

PubMed

Ohno, Naoki; Miyati, Tosiaki; Mase, Mitsuhito; Osawa, Tomoshi; Kan, Hirohito; Kasai, Harumasa; Hara, Masaki; Shibamoto, Yuta; Hayashi, Norio; Gabata, Toshifumi; Matsui, Osamu

2011-11-01

To determine whether temporal changes in apparent diffusion coefficient (ADC) over the cardiac cycle are different in patients with idiopathic normal-pressure hydrocephalus (INPH) as compared with patients with ex vacuo ventricular dilatation and healthy control subjects. This prospective study was approved by the institutional review board and was performed only after informed consent was obtained from each patient. At 1.5 T, electrocardiographically triggered single-shot diffusion echo-planar magnetic resonance imaging (b = 0 and 1000 sec/mm(2)) was performed with sensitivity encoding and half-scan techniques to minimize bulk motion. ΔADC was defined as the difference between maximum and minimum ADC on a pixel-by-pixel basis over 20 phases of the cardiac cycle. Mean ADC during the diastolic phase and ΔADC in the frontal white matter were determined in patients with INPH (n = 13), patients with ex vacuo ventricular dilatation (n = 8), and healthy volunteers (n = 10). Kruskal-Wallis tests were used to determine significance between groups. Mean ΔADC in the INPH group was significantly higher than that in the ex vacuo ventricular dilatation and control groups (P < .01 for both). There was no significant difference in ΔADC between the ex vacuo ventricular dilatation and control groups (P = .86). There was no significant difference in mean ADC during the diastolic phase among groups (P > .05 for all). There was no significant correlation between ΔADC and mean ADC during the diastolic phase in any group. Determination of fluctuation of ADC over the cardiac cycle may render it possible to noninvasively obtain new and more detailed information than that provided by standard ADC measurement in suspected INPH, potentially facilitating the diagnosis of this disease. RSNA, 2011

TU-H-CAMPUS-IeP2-01: Quantitative Evaluation of PROPELLER DWI Using QIBA Diffusion Phantom

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

Yung, J; Ai, H; Liu, H

Purpose: The purpose of this study is to determine the quantitative variability of apparent diffusion coefficient (ADC) values when varying imaging parameters in a diffusion-weighted (DW) fast spin echo (FSE) sequence with Periodically Rotated Overlapping ParallEL Lines with Enhanced Reconstruction (PROPELLER) k-space trajectory. Methods: Using a 3T MRI scanner, a NIST traceable, quantitative magnetic resonance imaging (MRI) diffusion phantom (High Precision Devices, Inc, Boulder, Colorado) consisting of 13 vials filled with various concentrations of polymer polyvinylpyrrolidone (PVP) in aqueous solution was imaged with a standard Quantitative Imaging Biomarkers Alliance (QIBA) DWI spin echo, echo planar imaging (SE EPI) acquisition. Themore » same phantom was then imaged with a DWI PROPELLER sequence at varying echo train lengths (ETL) of 8, 20, and 32, as well as b-values of 400, 900, and 2000. QIBA DWI phantom analysis software was used to generate ADC maps and create region of interests (ROIs) for quantitative measurements of each vial. Mean and standard deviations of the ROIs were compared. Results: The SE EPI sequence generated ADC values that showed very good agreement with the known ADC values of the phantom (r2 = 0.9995, slope = 1.0061). The ADC values measured from the PROPELLER sequences were inflated, but were highly correlated with an r2 range from 0.8754 to 0.9880. The PROPELLER sequence with an ETL=20 and b-value of 0 and 2000 showed the closest agreement (r2 = 0.9034, slope = 0.9880). Conclusion: The DW PROPELLER sequence is promising for quantitative evaluation of ADC values. A drawback of the PROPELLER sequence is the longer acquisition time. The 180° refocusing pulses may also cause the observed increase in ADC values compared to the standard SE EPI DW sequence. However, the FSE sequence offers an advantage with in-plane motion and geometric distortion which will be investigated in future studies.« less

A 9-Bit 50 MSPS Quadrature Parallel Pipeline ADC for Communication Receiver Application

NASA Astrophysics Data System (ADS)

Roy, Sounak; Banerjee, Swapna

2018-03-01

This paper presents the design and implementation of a pipeline Analog-to-Digital Converter (ADC) for superheterodyne receiver application. Several enhancement techniques have been applied in implementing the ADC, in order to relax the target specifications of its building blocks. The concepts of time interleaving and double sampling have been used simultaneously to enhance the sampling speed and to reduce the number of amplifiers used in the ADC. Removal of a front end sample-and-hold amplifier is possible by employing dynamic comparators with switched capacitor based comparison of input signal and reference voltage. Each module of the ADC comprises two 2.5-bit stages followed by two 1.5-bit stages and a 3-bit flash stage. Four such pipeline ADC modules are time interleaved using two pairs of non-overlapping clock signals. These two pairs of clock signals are in phase quadrature with each other. Hence the term quadrature parallel pipeline ADC has been used. These configurations ensure that the entire ADC contains only eight operational-trans-conductance amplifiers. The ADC is implemented in a 0.18-μm CMOS process and supply voltage of 1.8 V. The proto-type is tested at sampling frequencies of 50 and 75 MSPS producing an Effective Number of Bits (ENOB) of 6.86- and 6.11-bits respectively. At peak sampling speed, the core ADC consumes only 65 mW of power.

A 9-Bit 50 MSPS Quadrature Parallel Pipeline ADC for Communication Receiver Application

NASA Astrophysics Data System (ADS)

Roy, Sounak; Banerjee, Swapna

2018-06-01

This paper presents the design and implementation of a pipeline Analog-to-Digital Converter (ADC) for superheterodyne receiver application. Several enhancement techniques have been applied in implementing the ADC, in order to relax the target specifications of its building blocks. The concepts of time interleaving and double sampling have been used simultaneously to enhance the sampling speed and to reduce the number of amplifiers used in the ADC. Removal of a front end sample-and-hold amplifier is possible by employing dynamic comparators with switched capacitor based comparison of input signal and reference voltage. Each module of the ADC comprises two 2.5-bit stages followed by two 1.5-bit stages and a 3-bit flash stage. Four such pipeline ADC modules are time interleaved using two pairs of non-overlapping clock signals. These two pairs of clock signals are in phase quadrature with each other. Hence the term quadrature parallel pipeline ADC has been used. These configurations ensure that the entire ADC contains only eight operational-trans-conductance amplifiers. The ADC is implemented in a 0.18-μm CMOS process and supply voltage of 1.8 V. The proto-type is tested at sampling frequencies of 50 and 75 MSPS producing an Effective Number of Bits (ENOB) of 6.86- and 6.11-bits respectively. At peak sampling speed, the core ADC consumes only 65 mW of power.

Dynamic characteristics of MR diffusion-weighted imaging in a rabbit liver VX-2 tumor model.

PubMed

Yuan, You-Hong; Xiao, En-Hua; He, Zhong; Jin, Ke; Ma, Cong; Xiang, Jun; Xiao, Jian-Hua; Chen, Wei-Jian

2013-02-01

To investigate prospectively dynamic characteristics of the apparent diffusion coefficient (ADC) on MR diffusion-weighted imaging (DWI) in a rabbit VX-2 tumor model. Forty New Zealand rabbits were included in the study, and 47 rabbit VX-2 tumor models were developed by direct and intrahepatic implantation after opening the abdominal cavities. DWI was carried out periodically and respectively on days 7, 14 and 21 after implantation. The VX-2 tumor samples were studied by pathology. The distinction of VX-2 tumors on DWI was assessed by their ADC values by analysis of variance (ANOVA) using SPSS12.0 software. The ADC values (mean ± SD) × 10(-3) mm(2)/s of 47 VX-2 tumors in the peripheral and central areas were 2.18 ± 0.29, 1.96 ± 0.33, 1.80 ± 0.35, 2.20 ± 0.29, 2.05 ± 0.30 and 1.96 ± 0.48, respectively, on days 7, 14 and 21 after implantation. ADC values of 47 VX-2 tumors in the area of the tumor periphery, center and normal parenchyma were higher when the b-value was 100 s/mm(2) than those when the b-value was 300 s/mm(2) (F = 17.964, p < 0.001; F = 13.986, p < 0.001; F = 128.681, p < 0.001). ADC values in the area of normal liver parenchyma were higher than those in the area of the VX-2 tumor periphery and center when the b-value was 100 or 300 s/mm(2). ADCs of viable tumor cells in VX-2 tumors were lower on DWI than those in the area of normal liver parenchyma around the tumor, and ADCs of dead tumor cells in VX-2 tumors were unequal, including high, equal and low values, but they were higher than in the area of normal liver parenchyma around tumors after dead tumor cells had been liquefied or had become cystic. ADC is correlated with the tumor histology and degree of malignancy, and DWI has potential value for dynamically monitoring tumors and evaluating the degree of malignancy and therapeutic effect.

Communication Impairment in the AIDS Dementia Complex (ADC): A Case Report

ERIC Educational Resources Information Center

McCabe, Patricia J.; Sheard, Christine; Code, Chris

2008-01-01

This article details three examinations of communication impairment over 13 months in a man with AIDS dementia complex (ADC) and compares his performance on standardised language testing with that of two control participants. He had mild language impairments as measured on standardised tests but was severely impaired in pragmatic language skills.…

Is the necrosis/wall ADC ratio useful for the differentiation of benign and malignant breast lesions?

PubMed

Durur-Subasi, Irmak; Durur-Karakaya, Afak; Karaman, Adem; Seker, Mehmet; Demirci, Elif; Alper, Fatih

2017-05-01

To determine whether the necrosis/wall apparent diffusion coefficient (ADC) ratio is useful for the malignant-benign differentiation of necrotic breast lesions. Breast MRI was performed using a 3-T system. In this retrospective study, calculation of the necrosis/wall ADC ratio was based on ADC values measured from the necrosis and from the wall of malignant and benign breast lesions by diffusion-weighted imaging (DWI). By synchronizing post-contrast T 1 weighted images, the separate parts of wall and necrosis were maintained. All the diagnoses were pathologically confirmed. Statistical analyses were conducted using an independent sample t-test and receiver operating characteristic analysis. The intraclass and interclass correlations were evaluated. A total of 66 female patients were enrolled, 38 of whom had necrotic breast carcinomas and 28 of whom had breast abscesses. The ADC values were obtained from both the wall and necrosis. The mean necrosis/wall ADC ratio (± standard deviation) was 1.61 ± 0.51 in carcinomas, and it was 0.65 ± 0.33 in abscesses. The area under the curve values for necrosis ADC, wall ADC and the necrosis/wall ADC ratio were 0.680, 0.068 and 0.942, respectively. A wall/necrosis ADC ratio cut-off value of 1.18 demonstrated a sensitivity of 97%, specificity of 93%, a positive-predictive value of 95%, a negative-predictive value of 96% and an accuracy of 95% in determining the malignant nature of necrotic breast lesions. There was a good intra- and interclass reliability for the ADC values of both necrosis and wall. The necrosis/wall ADC ratio appears to be a reliable and promising tool for discriminating breast carcinomas from abscesses using DWI. Advances in knowledge: ADC values of the necrosis obtained by DWI are valuable for malignant-benign differentiation in necrotic breast lesions. The necrosis/wall ADC ratio appears to be a reliable and promising tool in the breast imaging field.

A Potential Mechanism for ADC-Induced Neutropenia: Role of Neutrophils in Their Own Demise.

PubMed

Zhao, Hui; Gulesserian, Sara; Malinao, Maria Christina; Ganesan, Sathish Kumar; Song, James; Chang, Mi Sook; Williams, Melissa M; Zeng, Zhilan; Mattie, Michael; Mendelsohn, Brian A; Stover, David R; Doñate, Fernando

2017-09-01

Neutropenia is a common adverse event in cancer patients treated with antibody-drug conjugates (ADC) and we aimed to elucidate the potential mechanism of this toxicity. To investigate whether ADCs affect neutrophil production from bone marrow, an in vitro assay was developed in which hematopoietic stem cells (HSC) were differentiated to neutrophils. Several antibodies against targets absent in HSCs and neutrophils were conjugated to MMAE via a cleavable valine-citrulline linker (vcMMAE-ADC) or MMAF via a noncleavable maleimidocaproyl linker (mcMMAF-ADC), and their cytotoxicity was tested in the neutrophil differentiation assay. Results showed that HSCs had similar sensitivity to vcMMAE-ADCs and mcMMAF-ADCs; however, vcMMAE-ADCs were more cytotoxic to differentiating neutrophils than the same antibody conjugated to mcMMAF. This inhibitory effect was not mediated by internalization of ADC either by macropinocytosis or FcγRs. Our results suggested that extracellular proteolysis of the cleavable valine-citrulline linker is responsible for the cytotoxicity to differentiating neutrophils. Mass spectrometry analyses indicated that free MMAE was released from vcMMAE-ADCs in the extracellular compartment when they were incubated with differentiating neutrophils or neutrophil conditioned medium, but not with HSC-conditioned medium. Using different protease inhibitors, our data suggested that serine, but not cysteine proteases, were responsible for the cleavage. In vitro experiments demonstrated that the purified serine protease, elastase, was capable of releasing free MMAE from a vcMMAE-ADC. Here we propose that ADCs containing protease cleavable linkers can contribute to neutropenia via extracellular cleavage mediated by serine proteases secreted by differentiating neutrophils in bone marrow. Mol Cancer Ther; 16(9); 1866-76. ©2017 AACR See related article by Zhao et al., p. 1877 . ©2017 American Association for Cancer Research.

Endometrial cancer: correlation of apparent diffusion coefficient (ADC) with tumor cellularity and tumor grade.

PubMed

Kishimoto, Keiko; Tajima, Shinya; Maeda, Ichiro; Takagi, Masayuki; Ueno, Takahiko; Suzuki, Nao; Nakajima, Yasuo

2016-08-01

Diffusion-weighted imaging (DWI) and the apparent diffusion coefficient (ADC) are widely used for detecting uterine endometrial cancer. The relationships between ADC values and pathological features of endometrial cancer have not yet been established. To investigate whether ADC values of endometrial cancer vary according to histologic tumor cellularity and tumor grade. We retrospectively reviewed 30 pathologically confirmed endometrial cancers. All patients underwent conventional non-enhanced magnetic resonance imaging (MRI) and DWI procedures, and ADC values were calculated. Tumor cellularity was evaluated by counting cancer cells in three high-power ( × 400) fields. The correlation between ADC values and tumor cellularity was assessed using Pearson's correlation coefficient test for statistical analysis. The mean ± standard deviation (SD) ADC value ( ×10(-3) mm(2)/s) of endometrial cancer was 0.85 ± 0.22 (range, 0.55-1.71). The mean ± SD tumor cellularity was 528.36 ± 16.89 (range, 298.0-763.6). ADC values were significantly inversely correlated with tumor cellularity. No significant relationship was observed between ADC values and tumor grade (mean ADC values: G1, 0.88 ± 0.265 × 10(-3) mm(2)/s; G2, 0.80 ± 0.178 × 10(-3) mm(2)/s; G3, 0.81 ± 0.117 × 10(-3) mm(2)/s). There is a significant inverse relationship between ADC values and tumor cellularity in endometrial cancer. No significant differences in average ADC value were observed between G1, G2, and G3 tumors. However, the lower the tumor grade, the wider the SD. © The Foundation Acta Radiologica 2015.

Diffusion-weighted MR imaging of the normal pancreas: reproducibility and variations of apparent diffusion coefficient measurement at 1.5- and 3.0-Tesla.

PubMed

Barral, M; Soyer, P; Ben Hassen, W; Gayat, E; Aout, M; Chiaradia, M; Rahmouni, A; Luciani, A

2013-04-01

To evaluate reproducibility and variations in apparent diffusion coefficient (ADC) measurement in normal pancreatic parenchyma at 1.5- and 3.0-Tesla and determine if differences may exist between the four pancreatic segments. Diffusion-weighted MR imaging of the pancreas was performed at 1.5-Tesla in 20 patients and at 3.0-Tesla in other 20 patients strictly matched for gender and age using the same b values (0, 400 and 800s/mm(2)). Two independent observers placed regions of interest within the four pancreatic segments to measure ADC at both fields. Intra- and inter-observer agreement in ADC measurement was assessed using Bland-Altman analysis and comparison between ADC values obtained at both fields using non-parametrical tests. There were no significant differences in ADC between repeated measurements and between ADC obtained at 1.5-Tesla and those at 3.0-Tesla. The 95% limits of intra-observer agreement between ADC were 2.3%-22.7% at 1.5-Tesla and 1%-24.2% at 3.0-Tesla and those for inter-observer agreement between 1.9%-14% at 1.5-Tesla and 8%-25% at 3.0-Tesla. ADC values were similar in all pancreatic segments at 3.0-T whereas the tail had lower ADC at 1.5-Tesla. ADC measurement conveys high degrees of intra- and inter-observer reproducibility. ADC have homogeneous distribution among the four pancreatic segments at 3.0-Tesla. Copyright © 2012 Éditions françaises de radiologie. Published by Elsevier Masson SAS. All rights reserved.

Image quality stability of whole-body diffusion weighted imaging.

PubMed

Chen, Yun-bin; Hu, Chun-miao; Zhong, Jing; Sun, Fei

2009-06-01

To assess the reproducibility of whole-body diffusion weighted imaging (WB-DWI) technique in healthy volunteers under normal breathing with background body signal suppression. WB-DWI was performed on 32 healthy volunteers twice within two-week period using short TI inversion-recovery diffusion-weighted echo-planar imaging sequence and built-in body coil. The volunteers were scanned across six stations continuously covering the entire body from the head to the feet under normal breathing. The bone apparent diffusion coefficient (ADC) and exponential ADC (eADC) of regions of interest (ROIs) were measured. We analyzed correlation of the results using paired-t-test to assess the reproducibility of the WB-DWI technique. We were successful in collecting and analyzing data of 64 WB-DWI images. There was no significant difference in bone ADC and eADC of 824 ROIs between the paired observers and paired scans (P>0.05). Most of the images from all stations were of diagnostic quality. The measurements of bone ADC and eADC have good reproducibility. WB-DWI technique under normal breathing with background body signal suppression is adequate.

High-throughput metabolic stability studies in drug discovery by orthogonal acceleration time-of-flight (OATOF) with analogue-to-digital signal capture (ADC).

PubMed

Temesi, David G; Martin, Scott; Smith, Robin; Jones, Christopher; Middleton, Brian

2010-06-30

Screening assays capable of performing quantitative analysis on hundreds of compounds per week are used to measure metabolic stability during early drug discovery. Modern orthogonal acceleration time-of-flight (OATOF) mass spectrometers equipped with analogue-to-digital signal capture (ADC) now offer performance levels suitable for many applications normally supported by triple quadruple instruments operated in multiple reaction monitoring (MRM) mode. Herein the merits of MRM and OATOF with ADC detection are compared for more than 1000 compounds screened in rat and/or cryopreserved human hepatocytes over a period of 3 months. Statistical comparison of a structurally diverse subset indicated good agreement for the two detection methods. The overall success rate was higher using OATOF detection and data acquisition time was reduced by around 20%. Targeted metabolites of diazepam were detected in samples from a CLint determination performed at 1 microM. Data acquisition by positive and negative ion mode switching can be achieved on high-performance liquid chromatography (HPLC) peak widths as narrow as 0.2 min (at base), thus enabling a more comprehensive first pass analysis with fast HPLC gradients. Unfortunately, most existing OATOF instruments lack the software tools necessary to rapidly convert the huge amounts of raw data into quantified results. Software with functionality similar to open access triple quadrupole systems is needed for OATOF to truly compete in a high-throughput screening environment. Copyright 2010 John Wiley & Sons, Ltd.

Assessing liver fibrosis: comparison of arterial enhancement fraction and diffusion-weighted imaging.

PubMed

Bonekamp, David; Bonekamp, Susanne; Ou, Hsin-You; Torbenson, Michael S; Corona-Villalobos, Celia Pamela; Mezey, Esteban; Kamel, Ihab R

2014-11-01

Noninvasive markers have been developed to reduce the need for liver biopsy. The aim of this study was to compare the strength of association of the arterial enhancement fraction (AEF), apparent diffusion coefficient (ADC), and serum biomarkers for staging hepatic fibrosis. Eighty-five patients with chronic liver disease underwent triple-phase contrast-enhanced MRI, used to calculate AEF, and diffusion-weighted MRI (b = 0,750 s/mm(2) ), used to calculate ADC. Hepatic fibrosis was staged according METAVIR criteria. The overall association of the four biomarkers (AEF, ADC, aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio, and aspartate aminotransferase to platelet ratio index [APRI]) was compared using nonparametric tests and receiver operating characteristic (ROC) curve, using histopathologic analysis as the reference standard. AEF and ADC values differed significantly between histopathologic fibrosis stages. AEF values correlated with fibrosis stage, ADC values correlated negatively with fibrosis stage. Compared with ADC, AEF showed a trend toward an improved capability of discriminating fibrosis stages. A weighted composite score of AEF and ADC had significantly better diagnostic accuracy than ADC alone (P ≤ 0.023). Imaging parameters had a significantly better diagnostic accuracy than AST/ALT ratio or APRI. AEF may be able to detect the presence of mild, moderate, and advanced liver fibrosis, and its value is increased with concomitant use of ADC. © 2013 Wiley Periodicals, Inc.

Confirmatory Factor Analysis and Test-Retest Reliability of the Alcohol and Drug Confrontation Scale (ADCS)

PubMed Central

Polcin, Douglas L.; Galloway, Gantt P.; Bond, Jason; Korcha, Rachael; Greenfield, Thomas K.

2008-01-01

The addiction field lacks an accepted definition and reliable measure of confrontation. The Alcohol and Drug Confrontation Scale (ADCS) defines confrontation as warnings about the potential consequences of substance use. To assess psychometric properties, 323 individual entering recovery houses in U.S. urban and suburban areas were interviewed between 2003 and 2005 (20% women, 68% white). Analyses included test-retest reliability, confirmatory factor analysis, and measures of internal consistency. Findings support the ADCS as a reliable way of assessing two factors: Internal Support and External intensity. Confrontation was experienced as supportive, accurate and helpful. Additional studies should assess confrontation in different contexts. PMID:20686635

Subtype Differentiation of Small (≤ 4 cm) Solid Renal Mass Using Volumetric Histogram Analysis of DWI at 3-T MRI.

PubMed

Li, Anqin; Xing, Wei; Li, Haojie; Hu, Yao; Hu, Daoyu; Li, Zhen; Kamel, Ihab R

2018-05-29

The purpose of this article is to evaluate the utility of volumetric histogram analysis of apparent diffusion coefficient (ADC) derived from reduced-FOV DWI for small (≤ 4 cm) solid renal mass subtypes at 3-T MRI. This retrospective study included 38 clear cell renal cell carcinomas (RCCs), 16 papillary RCCs, 18 chromophobe RCCs, 13 minimal fat angiomyolipomas (AMLs), and seven oncocytomas evaluated with preoperative MRI. Volumetric ADC maps were generated using all slices of the reduced-FOV DW images to obtain histogram parameters, including mean, median, 10th percentile, 25th percentile, 75th percentile, 90th percentile, and SD ADC values, as well as skewness, kurtosis, and entropy. Comparisons of these parameters were made by one-way ANOVA, t test, and ROC curves analysis. ADC histogram parameters differentiated eight of 10 pairs of renal tumors. Three subtype pairs (clear cell RCC vs papillary RCC, clear cell RCC vs chromophobe RCC, and clear cell RCC vs minimal fat AML) were differentiated by mean ADC. However, five other subtype pairs (clear cell RCC vs oncocytoma, papillary RCC vs minimal fat AML, papillary RCC vs oncocytoma, chromophobe RCC vs minimal fat AML, and chromophobe RCC vs oncocytoma) were differentiated by histogram distribution parameters exclusively (all p < 0.05). Mean ADC, median ADC, 75th and 90th percentile ADC, SD ADC, and entropy of malignant tumors were significantly higher than those of benign tumors (all p < 0.05). Combination of mean ADC with histogram parameters yielded the highest AUC (0.851; sensitivity, 80.0%; specificity, 86.1%). Quantitative volumetric ADC histogram analysis may help differentiate various subtypes of small solid renal tumors, including benign and malignant lesions.

Evaluation and validation of the diagnostic value of the apparent diffusion coefficient for differentiating early-stage endometrial carcinomas from benign mimickers at 3T MRI.

PubMed

Wang, Xue; Zhao, Yu; Hu, Yumin; Zhou, Yongjin; Ye, Xinjian; Liu, Kun; Bai, Guanghui; Guo, Anna; Du, Meimei; Jiang, Lezhen; Wang, Jinhong; Yan, Zhihan

2017-07-11

Previous researchers obtained various apparent diffusion coefficient (ADC) cutoff values to differentiate endometrial carcinoma from benign mimickers with 1.5T magnetic resonance imaging (MRI). Few studies have used 3T MRI or validated the effectiveness of these cutoff ADC values prospectively. This study was designed in two stages to obtain a cutoff ADC value at 3T MRI and to validate prospectively the role of the ADC value. First, we conducted a retrospective study of 60 patients to evaluate the diagnostic value of ADC by obtain a theoretical cutoff ADC value for differentiating between benign and malignant endometrial lesions. Student's t test revealed that ADC values for stage I endometrial carcinomas were significantly lower than those for benign lesions. The area under the curve value of the receiver operating characteristic curve was 0.993, and the cutoff ADC value was 0.98 × 10-3 mm2/s. The sensitivity, specificity, and overall accuracy of diagnosing stage I endometrial carcinoma were 100%, 97.1%, and 98.3%, respectively. Second, we conducted a prospective study of 26 patients to validate the use of the cutoff ADC value obtained in the study's first stage. The sensitivity, specificity, and overall accuracy for differentiating malignant from benign endometrial lesions based on the cutoff ADC value obtained earlier were as follows: radiologist 1 attained 86.67%, 100.0%, and 92.31%, respectively; radiologist 2 attained 86.67%, 91.0%, and 88.5%, respectively. Our results suggest that ADC values could be a potential biomarker for use as a quantitative and qualitative tool for differentiating between early-stage endometrial carcinomas and benign mimickers.

Evaluation and validation of the diagnostic value of the apparent diffusion coefficient for differentiating early-stage endometrial carcinomas from benign mimickers at 3T MRI

PubMed Central

Hu, Yumin; Zhou, Yongjin; Ye, Xinjian; Liu, Kun; Bai, Guanghui; Guo, Anna; Du, Meimei; Jiang, Lezhen

2017-01-01

Previous researchers obtained various apparent diffusion coefficient (ADC) cutoff values to differentiate endometrial carcinoma from benign mimickers with 1.5T magnetic resonance imaging (MRI). Few studies have used 3T MRI or validated the effectiveness of these cutoff ADC values prospectively. This study was designed in two stages to obtain a cutoff ADC value at 3T MRI and to validate prospectively the role of the ADC value. First, we conducted a retrospective study of 60 patients to evaluate the diagnostic value of ADC by obtain a theoretical cutoff ADC value for differentiating between benign and malignant endometrial lesions. Student's t test revealed that ADC values for stage I endometrial carcinomas were significantly lower than those for benign lesions. The area under the curve value of the receiver operating characteristic curve was 0.993, and the cutoff ADC value was 0.98 × 10−3 mm2/s. The sensitivity, specificity, and overall accuracy of diagnosing stage I endometrial carcinoma were 100%, 97.1%, and 98.3%, respectively. Second, we conducted a prospective study of 26 patients to validate the use of the cutoff ADC value obtained in the study's first stage. The sensitivity, specificity, and overall accuracy for differentiating malignant from benign endometrial lesions based on the cutoff ADC value obtained earlier were as follows: radiologist 1 attained 86.67%, 100.0%, and 92.31%, respectively; radiologist 2 attained 86.67%, 91.0%, and 88.5%, respectively. Our results suggest that ADC values could be a potential biomarker for use as a quantitative and qualitative tool for differentiating between early-stage endometrial carcinomas and benign mimickers. PMID:28634318

Ring Imaging Cerenkov Detector for CLAS12

NASA Astrophysics Data System (ADS)

Muhoza, Mireille; Aaron, Elise; Smoot, Waymond; Benmokhtar, Fatiha

2017-09-01

The CLAS12 detector at Thomas Jefferson National Accelerator Facility (TJNAF) is undergoing an upgrade. One of the additions to this detector is a Ring Imaging Cherenkov (RICH) detector to improve particle identification in the 3-8 GeV/c momentum range. Approximately 400 multi anode photomultiplier tubes (MAPMTs) will be used to detect Cherenkov Radiation in the single photoelectron spectra (SPS). Detector tests are taking place at Jefferson Lab, while analysis software development is ongoing at Duquesne. I will be summarizing the work done at Duquesne on the Database development and the analysis of the ADC and TDCs for the Hamamatsu Multi-Anode PMTs that are used for Cerenkov light radiation. National Science Foundation, Award 1615067.

Investigational Antibody-Drug Conjugates for Treatment of B-lineage Malignancies.

PubMed

Herrera, Alex F; Molina, Arturo

2018-05-10

Antibody-drug conjugates (ADCs) are tripartite molecules consisting of a monoclonal antibody, a covalent linker, and a cytotoxic payload. ADC development has aimed to target the specificity inherent in antigen-antibody interactions to deliver potent cytotoxins preferentially to tumor cells and maximize antitumor activity and simultaneously minimize off-target toxicity. The earliest ADCs provided disappointing results in the clinic; however, the lessons learned regarding the need for human or humanized antibodies, more stable linkers, and greater potency payloads led to improved ADCs. Three ADCs, gemtuzumab ozogamicin, brentuximab vedotin (BV), and inotuzumab ozogamicin, have been approved for hematologic malignancies. Site-specific conjugation methods have now resulted in a new generation of more uniform, molecularly defined ADCs. These are expected to display improved in vivo properties and have recently entered the clinic. We reviewed investigational ADCs currently in clinical testing for the treatment of B-cell lineage malignancies, including leukemias, lymphomas, and multiple myeloma. The rationales for antigen targeting, data reported to date, current trial status, and preclinical results for several newer ADCs expected to enter first-in-human studies are presented. Owing to the large number of ongoing and reported BV clinical studies, only the studies of BV for diffuse large B-cell lymphoma and those combining BV with checkpoint inhibitors in B-lineage malignancies have been reviewed. With > 40 ongoing clinical trials and 7 investigational ADCs already having advanced to phase II studies, the role of ADCs in the armamentarium for the treatment of B-lineage malignancies continues to be elucidated. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

A simple and versatile data acquisition system for software coincidence and pulse-height discrimination in 4πβ-γ coincidence experiments.

PubMed

Kawada, Y; Yamada, T; Unno, Y; Yunoki, A; Sato, Y; Hino, Y

2012-09-01

A simple but versatile data acquisition system for software coincidence experiments is described, in which any time stamping and live time controller are not provided. Signals from β- and γ-channels are fed to separately two fast ADCs (16 bits, 25 MHz clock maximum) via variable delay circuits and pulse-height stretchers, and also to pulse-height discriminators. The discriminating level was set to just above the electronic noise. Two ADCs were controlled with a common clock signal, and triggered simultaneously by the logic OR pulses from both discriminators. Paired digital signals for each sampling were sent to buffer memories connected to main PC with a FIFO (First-In, First-Out) pipe via USB. After data acquisition in list mode, various processing including pulse-height analyses was performed using MS-Excel (version 2007 and later). The usefulness of this system was demonstrated for 4πβ(PS)-4πγ coincidence measurements of (60)Co, (134)Cs and (152)Eu. Possibilities of other extended applications will be touched upon. Copyright © 2012 Elsevier Ltd. All rights reserved.

Is the necrosis/wall ADC ratio useful for the differentiation of benign and malignant breast lesions?

PubMed Central

Durur-Karakaya, Afak; Karaman, Adem; Seker, Mehmet; Demirci, Elif; Alper, Fatih

2017-01-01

Objective: To determine whether the necrosis/wall apparent diffusion coefficient (ADC) ratio is useful for the malignant–benign differentiation of necrotic breast lesions. Methods: Breast MRI was performed using a 3-T system. In this retrospective study, calculation of the necrosis/wall ADC ratio was based on ADC values measured from the necrosis and from the wall of malignant and benign breast lesions by diffusion-weighted imaging (DWI). By synchronizing post-contrast T1 weighted images, the separate parts of wall and necrosis were maintained. All the diagnoses were pathologically confirmed. Statistical analyses were conducted using an independent sample t-test and receiver operating characteristic analysis. The intraclass and interclass correlations were evaluated. Results: A total of 66 female patients were enrolled, 38 of whom had necrotic breast carcinomas and 28 of whom had breast abscesses. The ADC values were obtained from both the wall and necrosis. The mean necrosis/wall ADC ratio (± standard deviation) was 1.61 ± 0.51 in carcinomas, and it was 0.65 ± 0.33 in abscesses. The area under the curve values for necrosis ADC, wall ADC and the necrosis/wall ADC ratio were 0.680, 0.068 and 0.942, respectively. A wall/necrosis ADC ratio cut-off value of 1.18 demonstrated a sensitivity of 97%, specificity of 93%, a positive-predictive value of 95%, a negative-predictive value of 96% and an accuracy of 95% in determining the malignant nature of necrotic breast lesions. There was a good intra- and interclass reliability for the ADC values of both necrosis and wall. Conclusion: The necrosis/wall ADC ratio appears to be a reliable and promising tool for discriminating breast carcinomas from abscesses using DWI. Advances in knowledge: ADC values of the necrosis obtained by DWI are valuable for malignant-benign differentiation in necrotic breast lesions. The necrosis/wall ADC ratio appears to be a reliable and promising tool in the breast imaging field. PMID:28339285

An Open Hardware seismic data recorder - a solid basis for citizen science

NASA Astrophysics Data System (ADS)

Mertl, Stefan

2015-04-01

"Ruwai" is a 24-Bit Open Hardware seismic data recorder. It is built up of four stackable printed circuit boards fitting the Arduino Mega 2560 microcontroller prototyping platform. An interface to the BeagleBone Black single-board computer enables extensive data storage, -processing and networking capabilities. The four printed circuit boards provide a uBlox Lea-6T GPS module and real-time clock (GPS Timing shield), an Texas Instruments ADS1274 24-Bit analog to digital converter (ADC main shield), an analog input section with a Texas Instruments PGA281 programmable gain amplifier and an analog anti-aliasing filter (ADC analog interface pga) and the power conditioning based on 9-36V DC input (power supply shield). The Arduino Mega 2560 is used for controlling the hardware components, timestamping sampled data using the GPS timing information and transmitting the data to the BeagleBone Black single-board computer. The BeagleBone Black provides local data storage, wireless mesh networking using the optimized link state routing daemon and differential GNSS positioning using the RTKLIB software. The complete hardware and software is published under free software - or open hardware licenses and only free software (e.g. KiCad) was used for the development to facilitate the reusability of the design and increases the sustainability of the project. "Ruwai" was developed within the framework of the "Community Environmental Observation Network (CEON)" (http://www.mertl-research.at/ceon/) which was supported by the Internet Foundation Austria (IPA) within the NetIdee 2013 call.

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

Intravoxel Incoherent Motion and Quantitative Non-Gaussian Diffusion MR Imaging: Evaluation of the Diagnostic and Prognostic Value of Several Markers of Malignant and Benign Breast Lesions.

PubMed

Iima, Mami; Kataoka, Masako; Kanao, Shotaro; Onishi, Natsuko; Kawai, Makiko; Ohashi, Akane; Sakaguchi, Rena; Toi, Masakazu; Togashi, Kaori

2018-05-01

Purpose To investigate the performance of integrated approaches that combined intravoxel incoherent motion (IVIM) and non-Gaussian diffusion parameters compared with the Breast Imaging and Reporting Data System (BI-RADS) to establish multiparameter thresholds scores or probabilities by using Bayesian analysis to distinguish malignant from benign breast lesions and their correlation with molecular prognostic factors. Materials and Methods Between May 2013 and March 2015, 411 patients were prospectively enrolled and 199 patients (allocated to training [n = 99] and validation [n = 100] sets) were included in this study. IVIM parameters (flowing blood volume fraction [fIVIM] and pseudodiffusion coefficient [D*]) and non-Gaussian diffusion parameters (theoretical apparent diffusion coefficient [ADC] at b value of 0 sec/mm 2 [ADC 0 ] and kurtosis [K]) by using IVIM and kurtosis models were estimated from diffusion-weighted image series (16 b values up to 2500 sec/mm 2 ), as well as a synthetic ADC (sADC) calculated by using b values of 200 and 1500 (sADC 200-1500 ) and a standard ADC calculated by using b values of 0 and 800 sec/mm 2 (ADC 0-800 ). The performance of two diagnostic approaches (combined parameter thresholds and Bayesian analysis) combining IVIM and diffusion parameters was evaluated and compared with BI-RADS performance. The Mann-Whitney U test and a nonparametric multiple comparison test were used to compare their performance to determine benignity or malignancy and as molecular prognostic biomarkers and subtypes of breast cancer. Results Significant differences were found between malignant and benign breast lesions for IVIM and non-Gaussian diffusion parameters (ADC 0 , K, fIVIM, fIVIM · D*, sADC 200-1500, and ADC 0-800 ; P < .05). Sensitivity and specificity for the validation set by radiologists A and B were as follows: sensitivity, 94.7% and 89.5%, and specificity, 75.0% and 79.2% for sADC 200-1500 , respectively; sensitivity, 94.7% and 96.1%, and specificity, 75.0% and 66.7%, for the combined thresholds approach, respectively; sensitivity, 92.1% and 92.1%, and specificity, 83.3% and 66.7%, for Bayesian analysis, respectively; and sensitivity and specificity, 100% and 79.2%, for BI-RADS, respectively. The significant difference in values of sADC 200-1500 in progesterone receptor status (P = .002) was noted. sADC 200-1500 was significantly different between histologic subtypes (P = .006). Conclusion Approaches that combined various IVIM and non-Gaussian diffusion MR imaging parameters may provide BI-RADS-equivalent scores almost comparable to BI-RADS categories without the use of contrast agents. Non-Gaussian diffusion parameters also differed by biologic prognostic factors. © RSNA, 2017 Online supplemental material is available for this article.

Is it better to include necrosis in apparent diffusion coefficient (ADC) measurements? The necrosis/wall ADC ratio to differentiate malignant and benign necrotic lung lesions: Preliminary results.

PubMed

Karaman, Adem; Durur-Subasi, Irmak; Alper, Fatih; Durur-Karakaya, Afak; Subasi, Mahmut; Akgun, Metin

2017-10-01

To determine whether the use of necrosis/wall apparent diffusion coefficient (ADC) ratios in the differentiation of necrotic lung lesions is more reliable than measuring the wall alone. In this retrospective study, a total of 76 patients (54 males and 22 females, 71% vs. 29%, with a mean age of 53 ± 18 years, range, 18-84) were enrolled, 33 of whom had lung carcinoma and 43 had a benign necrotic lung lesion. A 3T scanner was used. The calculation of the necrosis/wall ADC ratio was based on ADC values measured from necrosis and the wall of the lesions by diffusion-weighted imaging (DWI). Statistical analyses were performed with the independent samples t-test and receiver operating characteristic analysis. Intraobserver and interobserver reliability were calculated for ADC values of wall and necrosis. The mean necrosis/wall ADC ratio was 1.67 ± 0.23 for malignant lesions and 0.75 ± 0.19 for benign lung lesions (P < 0.001). To estimate malignancy the area under the curve (AUC) values for necrosis ADC, wall ADC, and the necrosis/wall ADC ratio were 0.720, 0.073, and 0.997, respectively. A wall/necrosis ADC ratio cutoff value of 1.12 demonstrated a 100% sensitivity and 98% specificity in the estimation of malignancy. Positive predictive value was 100%, and negative predictive value 98% and diagnostic accuracy 99%. There was a good intraobserver and interobserver reliability for wall and necrosis. The necrosis/wall ADC ratio appears to be a reliable and promising tool for discriminating lung carcinoma from benign necrotic lung lesions than measuring the wall alone. 4 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2017;46:1001-1006. © 2017 International Society for Magnetic Resonance in Medicine.

Discussions on attitude determination and control system for micro/nano/pico-satellites considering survivability based on Hodoyoshi-3 and 4 experiences

NASA Astrophysics Data System (ADS)

Nakasuka, Shinichi; Miyata, Kikuko; Tsuruda, Yoshihiro; Aoyanagi, Yoshihide; Matsumoto, Takeshi

2018-04-01

The recent advancement of micro/nano/pico-satellites technologies encourages many universities to develop three axis stabilized satellites. As three axis stabilization is high level technology requiring the proper functioning of various sensors, actuators and control software, many early satellites failed in their initial operation phase because of shortage of solar power generation or inability to realize the initial step of missions because of unexpected attitude control system performance. These results come from failure to design the satellite attitude determination and control system (ADCS) appropriately and not considering "satellite survivability." ADCS should be designed such that even if some sensors or actuators cannot work as expected, the satellite can survive and carry out some of its missions, even if not full. This paper discusses how to realize ADCS while taking satellite survivability into account, based on our experiences of design and in-orbit operations of Hodoyoshi-3 and 4 satellites launched in 2014, which suffered from various component anomalies but could complete their missions.

Comparison of BOLD, diffusion-weighted fMRI and ADC-fMRI for stimulation of the primary visual system with a block paradigm.

PubMed

Nicolas, R; Gros-Dagnac, H; Aubry, F; Celsis, P

2017-06-01

The blood oxygen level-dependent (BOLD) effect is extensively used for functional MRI (fMRI) but presents some limitations. Diffusion-weighted fMRI (DfMRI) has been proposed as a method more tightly linked to neuronal activity. This work proposes a protocol of DfMRI acquired for several b-values and diffusion directions that is compared to gradient-echo BOLD (GE-BOLD) and to repeated spin-echo BOLD (SE-BOLD, acquisitions performed with b=0s/mm 2 ), which was also used to ensure the reproducibility of the response. A block stimulation paradigm of the primary visual system (V1) was performed in 12 healthy subjects with checkerboard alternations (2Hz frequency). DfMRI was performed at 3T with 5 b-values (b=1500, 1000, 500, 250, 0s/mm 2 ) with TR/TE=1004/93ms, Δ/δ=45.4ms/30ms, and 6 spatial directions for diffusion measures. GE-BOLD was performed with a similar block stimulation design timing. Apparent Diffusion Coefficient (ADC)-fMRI was computed with all b-values used. An identical Z-score level was used for all fMRI modalities for the comparison of volumes of activation. ADC-fMRI and SE-BOLD fMRI activation locations were compared in a voxel-based analysis to a cytoarchitectural probability map of V1. SE-BOLD activation volumes represented only 55% of the GE-BOLD activation volumes (P<0.0001). DfMRI activation volumes averaged for all b-values acquired represented only 12% of GE-BOLD (P<0.0001) and only 22% of SE-BOLD activation volumes (P<0.005). Compared to SE-BOLD-fMRI, ADC-fMRI activations showed fewer pixels outside of V1 and a higher average probability of belonging to V1. DfMRI and ADC-fMRI acquisition at 3T could be easily post-processed with common neuro-imaging software. DfMRI and ADC-fMRI activation volumes were significantly smaller than those obtained with SE-BOLD. ADC-fMRI activations were more precisely localized in V1 than those of SE-BOLD-fMRI. This validated the increased capability of ADC-fMRI compared to BOLD to enhance the precision of localizing an fMRI activation in the cyto-architectural zone V1, thereby justifying the use of ADC-fMRI for neuro-scientific studies. Copyright © 2017 Elsevier Inc. All rights reserved.

Apparent Diffusion Coefficient Values of the Benign Central Zone of the Prostate: Comparison With Low- and High-Grade Prostate Cancer.

PubMed

Gupta, Rajan T; Kauffman, Christopher R; Garcia-Reyes, Kirema; Palmeri, Mark L; Madden, John F; Polascik, Thomas J; Rosenkrantz, Andrew B

2015-08-01

The apparent diffusion coefficient (ADC) values for benign central zone (CZ) of the prostate were compared with ADC values of benign peripheral zone (PZ), benign transition zone (TZ), and prostate cancer, using histopathologic findings from radical prostatectomy as the reference standard. The study included 27 patients with prostate cancer (mean [± SD] age, 60.0 ± 7.6 years) who had 3-T endorectal coil MRI of the prostate performed before undergoing prostatectomy with whole-mount histopathologic assessment. Mean ADC values were recorded from the ROI within the index tumor and within benign CZ, PZ, and TZ, with the use of histopathologic findings as the reference standard. ADC values of the groups were compared using paired t tests and ROC curve analysis. The ADC of benign CZ in the right (1138 ± 123 × 10(-6) mm(2)/s) and left (1166 ± 141 × 10(-6) mm(2)/s) lobes was not significantly different (p = 0.217). However, the ADC of benign CZ (1154 ± 129 × 10(-6) mm(2)/s) was significantly lower (p < 0.001) than the ADCs of benign PZ (1579 ± 197 × 10(-6) mm(2)/s) and benign TZ (1429 ± 180 × 10(-6) mm(2)/s). Although the ADC of index tumors (1042 ± 134 × 10(-6) mm(2)/s) was significantly lower (p = 0.002) than the ADC of benign CZ there was no significant difference (p = 0.225) between benign CZ and tumors with a Gleason score of 6 (1119 ± 87 × 10(-6) mm(2)/s). In 22.2% of patients (6/27), including five patients who had tumors with a Gleason score greater than 6, the ADC was lower in benign CZ than in the index tumor. The AUC of ADC for the differentiation of benign CZ from index tumors was 72.4% (sensitivity, 70.4%; specificity, 51.9%), and the AUC of ADC for differentiation from tumors with a Gleason score greater than 6 was 76.7% (sensitivity, 75.0%; specificity, 65.0%). The ADC of benign CZ is lower than the ADC of other zones of the prostate and overlaps with the ADC of prostate cancer tissue, including high-grade tumors. Awareness of this potential diagnostic pitfall is important to avoid misinterpreting the normal CZ as suspicious for tumor.

Hepatocellular carcinoma: short-term reproducibility of apparent diffusion coefficient and intravoxel incoherent motion parameters at 3.0T.

PubMed

Kakite, Suguru; Dyvorne, Hadrien; Besa, Cecilia; Cooper, Nancy; Facciuto, Marcelo; Donnerhack, Claudia; Taouli, Bachir

2015-01-01

To evaluate short-term test-retest and interobserver reproducibility of IVIM (intravoxel incoherent motion) diffusion parameters and ADC (apparent diffusion coefficient) of hepatocellular carcinoma (HCC) and liver parenchyma at 3.0T. In this prospective Institutional Review Board (IRB)-approved study, 11 patients were scanned twice using a free-breathing single-shot echo-planar-imaging, diffusion-weighted imaging (DWI) sequence using 4 b values (b = 0, 50, 500, 1000 s/mm(2)) and IVIM DWI using 16 b values (0-800 s/mm(2)) at 3.0T. IVIM parameters (D: true diffusion coefficient, D*: pseudodiffusion coefficient, PF: perfusion fraction) and ADC (using 4 b and 16 b) were calculated. Short-term test-retest and interobserver reproducibility of IVIM parameters and ADC were assessed by measuring correlation coefficient, coefficient of variation (CV), and Bland-Altman limits of agreements (BA-LA). Fifteen HCCs were assessed in 10 patients. Reproducibility of IVIM metrics in HCC was poor for D* and PF (mean CV 60.6% and 37.3%, BA-LA: -161.6% to 135.3% and -66.2% to 101.0%, for D* and PF, respectively), good for D and ADC (CV 19.7% and <16%, BA-LA -57.4% to 36.3% and -38.2 to 34.1%, for D and ADC, respectively). Interobserver reproducibility was on the same order of test-retest reproducibility except for PF in HCC. Reproducibility of diffusion parameters was better in liver parenchyma compared to HCC. Poor reproducibility of D*/PF and good reproducibility for D/ADC were observed in HCC and liver parenchyma. These findings may have implications for trials using DWI in HCC. © 2014 Wiley Periodicals, Inc.

Test-retest reliability of diffusion tensor imaging of the liver at 3.0 T.

PubMed

Girometti, Rossano; Maieron, Marta; Lissandrello, Giovanni; Bazzocchi, Massimo; Zuiani, Chiara

2015-06-01

This study was done to evaluate test-retest reliability of liver diffusion tensor imaging (LDTI). Ten healthy volunteers (median age 23 years) underwent two LDTI scans on a 3.0 T magnet during two imaging sessions separated by 2 weeks (session-1/-2, respectively). Fifteen gradient directions and b values of 0-1,000 s/mm(2) were used. Two radiologists in consensus assessed liver apparent diffusion coefficient (ADC) and fraction of anisotropy (FA) values on ADC and FA maps at four reference levels, namely: right upper level (RUL), right lower level (RLL), left upper level (LUL) and left lower level (LLL). We then assessed (a) whether ADC and FA values overlapped when measured on different levels within the same imaging session or between different imaging sessions; (b) the degree of variability on an intra-session and inter-session basis, respectively, using the coefficient of variation (CV). In sessions 1 and 2, the ADC/FA values were significantly larger in the left liver lobe (LUL/LLL) compared to right liver lobe (RUL/RLL) (p < 0.05/6). Intra-session CVs were 9.51 % (session 1) and 9.73 % (session 2) for ADC, and 12.93 % (session 1) and 11.82 % (session 2) for FA, respectively. When comparing RUL, RLL, LUL and LLL on an inter-session basis, CVs were 6.52, 8.20, 6.52 and 11.06 % for ADC, and 15.42, 15.80, 15.42 and 6.80 % for FA, respectively. LDTI provides consistent and repeatable measurements. However, since larger left lobe ADC/FA values can be attributed to artefacts, right lobe values should be considered the most reliable measurements of water diffusivity within the liver.

Auto Code Generation for Simulink-Based Attitude Determination Control System

NASA Technical Reports Server (NTRS)

MolinaFraticelli, Jose Carlos

2012-01-01

This paper details the work done to auto generate C code from a Simulink-Based Attitude Determination Control System (ADCS) to be used in target platforms. NASA Marshall Engineers have developed an ADCS Simulink simulation to be used as a component for the flight software of a satellite. This generated code can be used for carrying out Hardware in the loop testing of components for a satellite in a convenient manner with easily tunable parameters. Due to the nature of the embedded hardware components such as microcontrollers, this simulation code cannot be used directly, as it is, on the target platform and must first be converted into C code; this process is known as auto code generation. In order to generate C code from this simulation; it must be modified to follow specific standards set in place by the auto code generation process. Some of these modifications include changing certain simulation models into their atomic representations which can bring new complications into the simulation. The execution order of these models can change based on these modifications. Great care must be taken in order to maintain a working simulation that can also be used for auto code generation. After modifying the ADCS simulation for the auto code generation process, it is shown that the difference between the output data of the former and that of the latter is between acceptable bounds. Thus, it can be said that the process is a success since all the output requirements are met. Based on these results, it can be argued that this generated C code can be effectively used by any desired platform as long as it follows the specific memory requirements established in the Simulink Model.

The design of 1-wire net meteorological observatory for 2.4 m telescope

NASA Astrophysics Data System (ADS)

Zhu, Gao-Feng; Wei, Ka-Ning; Fan, Yu-Feng; Xu, Jun; Qin, Wei

2005-03-01

The weather is an important factor to affect astronomical observations. The 2.4 m telescope can not work in Robotic Mode without the weather data input. Therefore it is necessary to build a meteorological observatory near the 2.4 m telescope. In this article, the design of the 1-wire net meteorological observatory, which includes hardware and software systems, is introduced. The hardware system is made up of some kinds of sensors and ADC. A suited power station system is also designed. The software system is based on Windows XP operating system and MySQL data management system, and a prototype system of browse/server model is developed by JAVA and JSP. After being tested, the meteorological observatory can register the immediate data of weather, such as raining, snowing, and wind speed. At last, the data will be stored for feature use. The product and the design can work well for the 2.4 m telescope.

Quantitative evaluation of benign and malignant vertebral fractures with diffusion-weighted MRI: what is the optimum combination of b values for ADC-based lesion differentiation with the single-shot turbo spin-echo sequence?

PubMed

Geith, Tobias; Schmidt, Gerwin; Biffar, Andreas; Dietrich, Olaf; Duerr, Hans Roland; Reiser, Maximilian; Baur-Melnyk, Andrea

2014-09-01

The purpose of our study was to determine the optimum combination of b values for calculating the apparent diffusion coefficient (ADC) using a diffusion-weighted (DW) single-shot turbo spin-echo (TSE) sequence in the differentiation between acute benign and malignant vertebral body fractures. Twenty-six patients with osteoporotic (mean age, 69 years; range, 31.5-86.2 years) and 20 patients with malignant vertebral fractures (mean age, 63.4 years; range, 24.7-86.4 years) were studied. T1-weighted, STIR, and T2-weighted sequences were acquired at 1.5 T. A DW single-shot TSE sequence at different b values (100, 250, 400, and 600 s/mm(2)) was applied. On the DW images for each evaluated fracture, an ROI was manually adapted to the area of hyperintense signal intensity on STIR-hypointense signal on T1-weighted images. For each ROI, nine different combinations of two, three, and four b values were used to calculate the ADC using a least-squares algorithm. The Student t test and Mann-Whitney U test were used to determine significant differences between benign and malignant fractures. An ROC analysis and the Youden index were used to determine cutoff values for assessment of the highest sensitivity and specificity for the different ADC values. The positive (PPV) and negative predictive values (NPV) were also determined. All calculated ADCs (except the combination of b = 400 s/mm(2) and b = 600 s/mm(2)) showed statistically significant differences between benign and malignant vertebral body fractures, with benign fractures having higher ADCs than malignant ones. The use of higher b values resulted in lower ADCs than those calculated with low b values. The highest AUC (0.85) showed the ADCs calculated with b = 100 and 400 s/mm(2), and the second highest AUC (0.829) showed the ADCs calculated with b = 100, 250, and 400 s/mm(2). The Youden index with equal weight given to sensitivity and specificity suggests use of an ADC calculated with b = 100, 250, and 400 s/mm(2) (cutoff ADC, < 1.7 × 10(-3) mm(2)/s) to best diagnose malignancy (sensitivity, 85%; specificity, 84.6%; PPV, 81.0%; NPV, 88.0%). ADCs calculated with a combination of low to intermediate b values (b = 100, 250, and 400 s/mm(2)) provide the best diagnostic performance of a DW single-shot TSE sequence to differentiate acute benign and malignant vertebral body fractures.

EGFR mutation incidence in non-small-cell lung cancer of adenocarcinoma histology: a systematic review and global map by ethnicity (mutMapII)

PubMed Central

Midha, Anita; Dearden, Simon; McCormack, Rose

2015-01-01

Mutations in the epidermal growth factor receptor (EGFR) gene are commonly observed in non-small-cell lung cancer (NSCLC), particularly in tumors of adenocarcinoma (ADC) histology (NSCLC/ADC). Robust data exist regarding the prevalence of EGFR mutations in Western and Asian patients with NSCLC/ADC, yet there is a lack of data for patients of other ethnicities. This review collated available data with the aim of creating a complete, global picture of EGFR mutation frequency in patients with NSCLC/ADC by ethnicity. Worldwide literature reporting EGFR mutation frequency in patients with NSCLC/ADC was reviewed, to create a map of the world populated with EGFR mutation frequency by country (a ‘global EGFR mutMap’). A total of 151 worldwide studies (n=33162 patients with NSCLC/ADC, of which 9749 patients had EGFR mutation-positive NSCLC/ADC) were included. There was substantial variation in EGFR mutation frequency between studies, even when grouped by geographic region or individual country. As expected, the Asia-Pacific NSCLC/ADC subgroup had the highest EGFR mutation frequency (47% [5958/12819; 87 studies; range 20%-76%]) and the lowest EGFR mutation frequency occurred in the Oceania NSCLC/ADC subgroup (12% [69/570; 4 studies; range 7%-36%]); however, comparisons between regions were limited due to the varying sizes of the patient populations studied. In all regional (geographic) subgroups where data were available, EGFR mutation frequency in NSCLC/ADC was higher in women compared with men, and in never-compared with ever-smokers. This review provides the foundation for a global map of EGFR mutation frequency in patients with NSCLC/ADC. The substantial lack of data from several large geographic regions of the world, notably Africa, the Middle East, Central Asia, and Central and South America, highlights a potential lack of routine mutation testing and the need for further investigations in these regions. PMID:26609494

A Novel Anti-CD22 Anthracycline-Based Antibody-Drug Conjugate (ADC) That Overcomes Resistance to Auristatin-Based ADCs.

PubMed

Yu, Shang-Fan; Zheng, Bing; Go, MaryAnn; Lau, Jeff; Spencer, Susan; Raab, Helga; Soriano, Robert; Jhunjhunwala, Suchit; Cohen, Robert; Caruso, Michele; Polakis, Paul; Flygare, John; Polson, Andrew G

2015-07-15

We are interested in identifying mechanisms of resistance to the current generation of antibody-drug conjugates (ADC) and developing ADCs that can overcome this resistance. Pinatuzumab vedotin (anti-CD22-vc-MMAE) and polatuzumab vedotin (anti-CD79b-vc-MMAE) are ADCs that contain the microtubule inhibitor monomethyl auristatin E (MMAE) attached to the antibody by the protease-cleavable linker maleimidocaproyl-valine-citrulline-p-aminobenzoyloxycarbonyl (MC-vc-PAB). Early clinical trial data suggest that these ADCs have promising efficacy for the treatment of non-Hodgkin lymphoma (NHL); however, some patients do not respond or become resistant to the ADCs. Anthracyclines are very effective in NHL, but ADCs containing the anthracycline doxorubicin were not clinically efficacious probably due to the low drug potency and inadequate linker technology. The anthracycline analogue PNU-159682 is thousands of times more cytotoxic than doxorubicin, so we used it to develop a new class of ADCs. We used the same MC-vc-PAB linker and antibody in pinatuzumab vedotin but replaced the MMAE with a derivative of PNU-159682 to make anti-CD22-NMS249 and tested it for in vivo efficacy in xenograft tumors resistant to MMAE-based ADCs. We derived cell lines from in vivo xenograft tumors that were made resistant to anti-CD22-vc-MMAE and anti-CD79b-vc-MMAE. We identified P-gp (ABCB1/MDR1) as the major driver of resistance to the vc-MMAE-based conjugates. Anti-CD22-NMS249 was at least as effective as anti-CD22-vc-MMAE in xenograft models of the parental cell lines and maintained its efficacy in the resistant cell lines. These studies provide proof of concept for an anthracycline-based ADC that could be used to treat B-cell malignancies that are resistant to vc-MMAE conjugates. ©2015 American Association for Cancer Research.

Implementation of Advanced Inventory Management Functionality in Automated Dispensing Cabinets

PubMed Central

Webb, Aaron; Lund, Jim

2015-01-01

Background: Automated dispensing cabinets (ADCs) are an integral component of distribution models in pharmacy departments across the country. There are significant challenges to optimizing ADC inventory management while minimizing use of labor and capital resources. The role of enhanced inventory control functionality is not fully defined. Objective: The aim of this project is to improve ADC inventory management by leveraging dynamic inventory standards and a low inventory alert platform. Methods: Two interventional groups and 1 historical control were included in the study. Each intervention group consisted of 6 ADCs that tested enhanced inventory management functionality. Interventions included dynamic inventory standards and a low inventory alert messaging system. Following separate implementation of each platform, dynamic inventory and low inventory alert systems were applied concurrently to all 12 ADCs. Outcome measures included number and duration of daily stockouts, ADC inventory turns, and number of phone calls related to stockouts received by pharmacy staff. Results: Low inventory alerts reduced both the number and duration of stockouts. Dynamic inventory standards reduced the number of daily stockouts without changing the inventory turns and duration of stockouts. No change was observed in number of calls related to stockouts made to pharmacy staff. Conclusions: Low inventory alerts and dynamic inventory standards are feasible mechanisms to help optimize ADC inventory management while minimizing labor and capital resources. PMID:26448672

Delta Modulation Technique for Improving the Sensitivity of Monobit Subsamplers in Radar and Coherent Receiver Applications

DOE PAGES

Rodenbeck, Christopher T.; Tracey, Keith J.; Barkley, Keith R.; ...

2014-08-01

This paper introduces a technique for improving the sensitivity of RF subsamplers in radar and coherent receiver applications. The technique, referred to herein as “delta modulation” (DM), feeds the time-average output of a monobit analog-to-digital converter (ADC) back to the ADC input, but with opposite polarity. Assuming pseudo-stationary modulation statistics on the sampled RF waveform, the feedback signal corrects for aggregate DC offsets present in the ADC that otherwise degrade ADC sensitivity. Two RF integrated circuits (RFICs) are designed to demonstrate the approach. One uses analog DM to create the feedback signal; the other uses digital DM to achieve themore » same result. A series of tests validates the designs. The dynamic time-domain response confirms the feedback loop’s basic operation. Measured output quantization imbalance, under noise-only input drive, significantly improves with the use of the DM circuit, even for large, deliberately induced DC offsets and wide temperature variation from -55°C to +85 °C. Examination of the corrected vs. uncorrected baseband spectrum under swept input signal-tonoise ratio (SNR) conditions demonstrates the effectiveness of this approach for realistic radar and coherent receiver applications. In conclusion, two-tone testing shows no impact of the DM technique on ADC linearity.« less

Considerations for the nonclinical safety evaluation of antibody drug conjugates for oncology.

PubMed

Roberts, Stanley A; Andrews, Paul A; Blanset, Diann; Flagella, Kelly M; Gorovits, Boris; Lynch, Carmel M; Martin, Pauline L; Kramer-Stickland, Kimberly; Thibault, Stephane; Warner, Garvin

2013-12-01

Antibody drug conjugates (ADCs) include monoclonal antibodies that are linked to cytotoxic small molecules. A number of these agents are currently being developed as anti-cancer agents designed to improve the therapeutic index of the cytotoxin (i.e., cytotoxic small molecule or cytotoxic agent) by specifically delivering it to tumor cells. This paper presents primary considerations for the nonclinical safety evaluation of ADCs and includes strategies for the evaluation of the entire ADC or the various individual components (i.e., antibody, linker or the cytotoxin). Considerations are presented on how to design a nonclinical safety assessment program to identify the on- and off-target toxicities to enable first-in-human (FIH) studies. Specific discussions are also included that provide details as to the need and how to conduct the studies for evaluating ADCs in genetic toxicology, tissue cross-reactivity, safety pharmacology, carcinogenicity, developmental and reproductive toxicology, biotransformation, toxicokinetic monitoring, bioanalytical assays, immunogenicity testing, test article stability and the selection of the FIH dose. Given the complexity of these molecules and our evolving understanding of their properties, there is no single all-encompassing nonclinical strategy. Instead, each ADC should be evaluated on a case-by-case scientifically-based approach that is consistent with ICH and animal research guidelines. Copyright © 2013 Elsevier Inc. All rights reserved.

Development of a hardware-in-loop attitude control simulator for a CubeSat satellite

NASA Astrophysics Data System (ADS)

Tapsawat, Wittawat; Sangpet, Teerawat; Kuntanapreeda, Suwat

2018-01-01

Attitude control is an important part in satellite on-orbit operation. It greatly affects the performance of satellites. Testing of an attitude determination and control subsystem (ADCS) is very challenging since it might require attitude dynamics and space environment in the orbit. This paper develops a low-cost hardware-in-loop (HIL) simulator for testing an ADCS of a CubeSat satellite. The simulator consists of a numerical simulation part, a hardware part, and a HIL interface hardware unit. The numerical simulation part includes orbital dynamics, attitude dynamics and Earth’s magnetic field. The hardware part is the real ADCS board of the satellite. The simulation part outputs satellite’s angular velocity and geomagnetic field information to the HIL interface hardware. Then, based on this information, the HIL interface hardware generates I2C signals mimicking the signals of the on-board rate-gyros and magnetometers and consequently outputs the signals to the ADCS board. The ADCS board reads the rate-gyro and magnetometer signals, calculates control signals, and drives the attitude actuators which are three magnetic torquers (MTQs). The responses of the MTQs sensed by a separated magnetometer are feedback to the numerical simulation part completing the HIL simulation loop. Experimental studies are conducted to demonstrate the feasibility and effectiveness of the simulator.

Does apparent diffusion coefficient predict the degree of liver regeneration of donor and recipient after living donor liver transplantation?

PubMed

Morita, Koichiro; Nishie, Akihiro; Asayama, Yoshiki; Ishigami, Kousei; Ushijima, Yasuhiro; Takayama, Yukihisa; Okamoto, Daisuke; Fujita, Nobuhiro; Ikegami, Toru; Yoshizumi, Tomoharu; Shirabe, Ken; Honda, Hiroshi

2017-05-01

To elucidate the relationship between the ADCs of the liver graft and the remnant liver and the degree of liver regeneration in LDLT. 15 recipients and 15 corresponding donors underwent magnetic resonance imaging and computed tomography 1-2 weeks after living donor liver transplantation (LDLT). For diffusion-weighted imaging (DWI), a single-shot echo-planar sequence with b-factors of 0, 500, and 1000s/mm 2 was scanned. ADCs of the liver parenchyma were calculated at b factors of 0 and 500 and 1000 (ADC 0-500-1000) or 0 and 500 (ADC 0-500) or 500 and 1000 (ADC 500-1000). The liver volume ratio at LDLT, the mean ADCs and the regeneration rate were compared between the graft and the remnant liver using paired-t tests. The mean liver volume ratio of the recipients (41.3±9.8%) tended to be smaller than that of the donors (51.8±13.8%). The mean ADC 0-500 of the remnant liver (1.72±0.33) was significantly higher than that of the graft (1.43±0.32). The regeneration rate of the graft (2.07±0.41) was significantly higher than that of the remnant liver (1.53±0.49). ADC 0-500 can describe differences in blood perfusion between liver grafts and the remnant liver according to the degree of liver regeneration. Copyright © 2017 Elsevier B.V. All rights reserved.

The value of multi ultra high-b-value DWI in grading cerebral astrocytomas and its association with aquaporin-4.

PubMed

Tan, Yan; Zhang, Hui; Wang, Xiao-Chun; Qin, Jiang-Bo; Wang, Le

2018-06-01

To investigate the value of multi-ultrahigh-b-value diffusion-weighted imaging (UHBV-DWI) in differentiating high-grade astrocytomas (HGAs) from low-grade astrocytomas (LGAs), analyze its association with aquaporin (AQP) expression. 40 astrocytomas divided into LGAs (N = 15) and HGAs (N = 25) were studied. Apparent diffusion coefficient (ADC) and UHBV-ADC values in solid parts and peritumoral edema were compared between LGAs and HGAs groups by the t-test. Using receiver operating characteristic curves to identify the better parameter. Using real time polymerase chain reaction to assess AQP messenger ribonucleic acid (mRNA). Using spearman correlation analysis to assess the correlation of AQP mRNA with each parameter. ADC values in solid parts of HGAs were significantly lower than LGAs (p = 0.02), while UHBV-ADC values of HGAs were significantly higher than LGAs (p < 0.01). Area under the curve (AUC) of UHBV-ADC (0.810) was larger than ADC (0.713), and the area under the curve of UHBV-ADC was significantly higher than that of ADC (p = 0.041). AQP4 mRNA was significantly higher in HGAs than that in LGAs (p < 0.01); there was less AQP9 mRNA and no AQP1 mRNA in LGAs and HGAs groups (p > 0.05); ADC value showed a negative correlation with AQP4 mRNA (r = -0.357; p = 0.024). UHBV-ADC value positively correlated with the AQP4 mRNA (r = 0.646; p < 0.01). UHBV-DWI allowed for a more accurate grading of cerebral astrocytoma than DWI, and UHBV-ADC value may be related with the AQP4 mRNA levels. UHBV-DWI could be of value in the assessment of astrocytoma. Advances in knowledge: UHBV-DWI generated by multi UHBV could have particular value for astrocytoma grading, and the level of AQP4 mRNA might be potentially linked to the change of UHBV-DWI parameter, and we might find the exact reason for the difference of UHBV-ADC between the LGAs and HGAs.

JSATS Detector Field Manual

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

Choi, Eric Y.; Flory, Adam E.; Lamarche, Brian L.

2014-06-01

The Juvenile Salmon Acoustic Telemetry System (JSATS) Detector is a software and hardware system that captures JSATS Acoustic Micro Transmitter (AMT) signals. The system uses hydrophones to capture acoustic signals in the water. This analog signal is then amplified and processed by the Analog to Digital Converter (ADC) and Digital Signal Processor (DSP) board in the computer. This board digitizes and processes the acoustic signal to determine if a possible JSATS tag is present. With this detection, the data will be saved to the computer for further analysis. This document details the features and functionality of the JSATS Detector software.more » The document covers how to install the software, setup and run the detector software. The document will also go over the raw binary waveform file format and CSV files containing RMS values« less

DWI-associated entire-tumor histogram analysis for the differentiation of low-grade prostate cancer from intermediate-high-grade prostate cancer.

PubMed

Wu, Chen-Jiang; Wang, Qing; Li, Hai; Wang, Xiao-Ning; Liu, Xi-Sheng; Shi, Hai-Bin; Zhang, Yu-Dong

2015-10-01

To investigate diagnostic efficiency of DWI using entire-tumor histogram analysis in differentiating the low-grade (LG) prostate cancer (PCa) from intermediate-high-grade (HG) PCa in comparison with conventional ROI-based measurement. DW images (b of 0-1400 s/mm(2)) from 126 pathology-confirmed PCa (diameter >0.5 cm) in 110 patients were retrospectively collected and processed by mono-exponential model. The measurement of tumor apparent diffusion coefficients (ADCs) was performed with using histogram-based and ROI-based approach, respectively. The diagnostic ability of ADCs from two methods for differentiating LG-PCa (Gleason score, GS ≤ 6) from HG-PCa (GS > 6) was determined by ROC regression, and compared by McNemar's test. There were 49 LG-tumor and 77 HG-tumor at pathologic findings. Histogram-based ADCs (mean, median, 10th and 90th) and ROI-based ADCs (mean) showed dominant relationships with ordinal GS of Pca (ρ = -0.225 to -0.406, p < 0.05). All above imaging indices reflected significant difference between LG-PCa and HG-PCa (all p values <0.01). Histogram 10th ADCs had dominantly high Az (0.738), Youden index (0.415), and positive likelihood ratio (LR+, 2.45) in stratifying tumor GS against mean, median and 90th ADCs, and ROI-based ADCs. Histogram mean, median, and 10th ADCs showed higher specificity (65.3%-74.1% vs. 44.9%, p < 0.01), but lower sensitivity (57.1%-71.3% vs. 84.4%, p < 0.05) than ROI-based ADCs in differentiating LG-PCa from HG-PCa. DWI-associated histogram analysis had higher specificity, Az, Youden index, and LR+ for differentiation of PCa Gleason grade than ROI-based approach.

Can histogram analysis of MR images predict aggressiveness in pancreatic neuroendocrine tumors?

PubMed

De Robertis, Riccardo; Maris, Bogdan; Cardobi, Nicolò; Tinazzi Martini, Paolo; Gobbo, Stefano; Capelli, Paola; Ortolani, Silvia; Cingarlini, Sara; Paiella, Salvatore; Landoni, Luca; Butturini, Giovanni; Regi, Paolo; Scarpa, Aldo; Tortora, Giampaolo; D'Onofrio, Mirko

2018-06-01

To evaluate MRI derived whole-tumour histogram analysis parameters in predicting pancreatic neuroendocrine neoplasm (panNEN) grade and aggressiveness. Pre-operative MR of 42 consecutive patients with panNEN >1 cm were retrospectively analysed. T1-/T2-weighted images and ADC maps were analysed. Histogram-derived parameters were compared to histopathological features using the Mann-Whitney U test. Diagnostic accuracy was assessed by ROC-AUC analysis; sensitivity and specificity were assessed for each histogram parameter. ADC entropy was significantly higher in G2-3 tumours with ROC-AUC 0.757; sensitivity and specificity were 83.3 % (95 % CI: 61.2-94.5) and 61.1 % (95 % CI: 36.1-81.7). ADC kurtosis was higher in panNENs with vascular involvement, nodal and hepatic metastases (p= .008, .021 and .008; ROC-AUC= 0.820, 0.709 and 0.820); sensitivity and specificity were: 85.7/74.3 % (95 % CI: 42-99.2 /56.4-86.9), 36.8/96.5 % (95 % CI: 17.2-61.4 /76-99.8) and 100/62.8 % (95 % CI: 56.1-100/44.9-78.1). No significant differences between groups were found for other histogram-derived parameters (p >.05). Whole-tumour histogram analysis of ADC maps may be helpful in predicting tumour grade, vascular involvement, nodal and liver metastases in panNENs. ADC entropy and ADC kurtosis are the most accurate parameters for identification of panNENs with malignant behaviour. • Whole-tumour ADC histogram analysis can predict aggressiveness in pancreatic neuroendocrine neoplasms. • ADC entropy and kurtosis are higher in aggressive tumours. • ADC histogram analysis can quantify tumour diffusion heterogeneity. • Non-invasive quantification of tumour heterogeneity can provide adjunctive information for prognostication.

Progress in Low-Power Digital Microwave Radiometer Technologies

NASA Technical Reports Server (NTRS)

Piepmeier, Jeffrey R.; Kim, Edward J.

2004-01-01

Three component technologies were combined into a digital correlation microwave radiometer. The radiometer comprises a dual-channel X-band superheterodyne receiver, low-power high-speed cross-correlator (HSCC), three-level ADCs, and a correlated noise source (CNS). The HSCC dissipates 10 mW and operates at 500 MHz clock speed. The ADCs are implemented using ECL components and dissipate more power than desired. Thus, a low-power ADC development is underway. The new ADCs arc predicted to dissipated less than 200 mW and operate at 1 GSps with 1.5 GHz of input bandwidth. The CNS provides different input correlation values for calibration of the radiometer. The correlation channel had a null offset of 0.0008. Test results indicate that the correlation channel can be calibrated with 0.09% error in gain.

A parallel unbalanced digitization architecture to reduce the dynamic range of multiple signals

NASA Astrophysics Data System (ADS)

Vallérian, Mathieu; HuÅ£u, Florin; Villemaud, Guillaume; Miscopein, Benoît; Risset, Tanguy

2016-05-01

Technologies employed in urban sensor networks are permanently evolving, and thus the gateways employed to collect data in such kind of networks have to be very flexible in order to be compliant with the new communication standards. A convenient way to do that is to digitize all the received signals in one shot and then to digitally perform the signal processing, as it is done in software-defined radio (SDR). All signals can be emitted with very different features (bandwidth, modulation type, and power level) in order to respond to the various propagation conditions. Their difference in terms of power levels is a problem when digitizing them together, as no current commercial analog-to-digital converter (ADC) can provide a fine enough resolution to digitize this high dynamic range between the weakest possible signal in the presence of a stronger signal. This paper presents an RF front end receiver architecture capable of handling this problem by using two ADCs of lower resolutions. The architecture is validated through a set of simulations using Keysight's ADS software. The main validation criterion is the bit error rate comparison with a classical receiver.

Activated matriptase as a target to treat breast cancer with a drug conjugate

PubMed Central

Lin, Hongxia; Banach-Petrosky, Whitney; Hirshfield, Kim M.; Lin, Chen-Yong; Johnson, Michael D.; Szekely, Zoltan; Bertino, Joseph R.

2018-01-01

The antitumor effects of a novel antibody drug conjugate (ADC) was tested against human solid tumor cell lines and against human triple negative breast cancer (TNBC) xenografts in immunosuppressed mice. The ADC targeting activated matriptase of tumor cells was synthesized by using the potent anti-tubulin toxin, monomethyl auristatin-E linked to the activated matriptase-specific monoclonal antibody (M69) via a lysosomal protease-cleavable dipeptide linker. This ADC was found to be cytotoxic against multiple activated matriptase-positive epithelial carcinoma cell lines in vitro and markedly inhibited growth of triple negative breast cancer xenografts and a primary human TNBC (PDX) in vivo. Overexpression of activated matriptase may be a biomarker for response to this ADC. The ADC had potent anti-tumor activity, while the unconjugated M69 antibody was ineffective in a mouse model study using MDA-MB-231 xenografts in mice. Treatment of a human TNBC (MDA-MB-231) showed potent anti-tumor effects in combination with cisplatin in mice. This ADC alone or in combination with cisplatin has the potential to improve the treatment outcomes of patients with TNBC as well as other tumors overexpressing activated matriptase. PMID:29899836

Impact of ADC parameters on linear optical sampling systems

NASA Astrophysics Data System (ADS)

Nguyen, Trung-Hien; Gay, Mathilde; Gomez-Agis, Fausto; Lobo, Sébastien; Sentieys, Olivier; Simon, Jean-Claude; Peucheret, Christophe; Bramerie, Laurent

2017-11-01

Linear optical sampling (LOS), based on the coherent photodetection of an optical signal under test with a low repetition-rate signal originating from a pulsed local oscillator (LO), enables the characterization of the temporal electric field of optical sources. Thanks to this technique, low-speed photodetectors and analog-to-digital converters (ADCs) can be integrated in the LOS system providing a cost-effective tool for characterizing high-speed signals. However, the impact of photodetector and ADC parameters on such LOS systems has not been explored in detail so far. These parameters, including the integration time of the track-and-hold function, the effective number of bits (ENOB) of the ADC, as well as the combined limited bandwidth of the photodetector and ADC are experimentally and numerically investigated in a LOS system for the first time. More specifically, by reconstructing 10-Gbit/s non-return-to-zero on-off keying (NRZ-OOK) and 10-Gbaud NRZ-quadrature phase-shift-keying (QPSK) signals, it is shown that a short integration time provides a better recovered signal fidelity. Furthermore, an ENOB of 6 bits and an ADC bandwidth normalized to the sampling rate of 2.8 are found to be sufficient in order to reliably monitor the considered signals.

Evaluation of Free Breathing Versus Breath Hold Diffusion Weighted Imaging in Terms Apparent Diffusion Coefficient (ADC) and Signal-to-Noise Ratio (SNR) Values for Solid Abdominal Organs.

PubMed

Herek, Duygu; Karabulut, Nevzat; Kocyıgıt, Ali; Yagcı, Ahmet Baki

2016-01-01

Our aim was to compare the apparent diffusion coefficient (ADC) values of normal abdominal parenchymal organs and signal-to-noise ratio (SNR) measurements in the same patients with breath hold (BH) and free breathing (FB) diffusion weighted imaging (DWI). Forty-eight patients underwent both BH and FB DWI. Spherical region of interest (ROI) was placed on the right hepatic lobe, spleen, pancreas, and renal cortices. ADC values were calculated for each organ on each sequence using an automated software. Image noise, defined as the standard deviation (SD) of the signal intensities in the most artifact-free area of the image background was measured by placing the largest possible ROI on either the left or the right side of the body outside the object in the recorded field of view. SNR was calculated using the formula: SNR=signal intensity (SI) (organ) /standard deviation (SD) (noise) . There were no statistically significant differences in ADC values of the abdominal organs between BH and FB DWI sequences ( p >0.05). There were statistically significant differences between SNR values of organs on BH and FB DWIs. SNRs were found to be better on FB DWI than BH DWI ( p <0.001). Free breathing DWI technique reduces image noise and increases SNR for abdominal examinations. Free breathing technique is therefore preferable to BH DWI in the evaluation of abdominal organs by DWI.

Apparent diffusion coefficient as it relates to histopathology findings in post-chemotherapy nephroblastoma: a feasibility study.

PubMed

Littooij, Annemieke S; Nikkels, Peter G; Hulsbergen-van de Kaa, Christina A; van de Ven, Cees P; van den Heuvel-Eibrink, Marry M; Olsen, Øystein E

2017-11-01

Nephroblastomas represent a group of heterogeneous tumours with variable proportions of distinct histopathological components. The purpose of this study was to investigate whether direct comparison of apparent diffusion coefficient (ADC) measurements with post-resection histopathology subtypes is feasible and whether ADC metrics are related to histopathological components. Twenty-three children were eligible for inclusion in this retrospective study. All children had MRI including diffusion-weighted imaging (DWI) after preoperative chemotherapy, just before tumour resection. A pathologist and radiologist identified corresponding slices at MRI and postoperative specimens using tumour morphology, the upper/lower calyx and hilar vessels as reference points. An experienced reader performed ADC measurements, excluding non-enhancing areas. A pathologist reviewed the corresponding postoperative slides according to the international standard guidelines. We tested potential associations with the Spearman rank test. Side-by-side comparison of MRI-DWI with corresponding histopathology slides was feasible in 15 transverse slices in 9 lesions in 8 patients. Most exclusions were related to extensive areas of necrosis/haemorrhage. In one lesion correlation was not possible because of the different orientation of sectioning of the specimen and MRI slices. The 25% ADC showed a strong relationship with percentage of blastema (Spearman rho=-0.71, P=0.003), whereas median ADC was strongly related to the percentage stroma (Spearman rho=0.74, P=0.002) at histopathology. Side-by-side comparison of MRI-DWI and histopathology is feasible in the majority of patients who do not have massive necrosis and hemorrhage. Blastemal and stromal components have a strong linear relationship with ADC markers.

QIN DAWG Validation of Gradient Nonlinearity Bias Correction Workflow for Quantitative Diffusion-Weighted Imaging in Multicenter Trials.

PubMed

Malyarenko, Dariya I; Wilmes, Lisa J; Arlinghaus, Lori R; Jacobs, Michael A; Huang, Wei; Helmer, Karl G; Taouli, Bachir; Yankeelov, Thomas E; Newitt, David; Chenevert, Thomas L

2016-12-01

Previous research has shown that system-dependent gradient nonlinearity (GNL) introduces a significant spatial bias (nonuniformity) in apparent diffusion coefficient (ADC) maps. Here, the feasibility of centralized retrospective system-specific correction of GNL bias for quantitative diffusion-weighted imaging (DWI) in multisite clinical trials is demonstrated across diverse scanners independent of the scanned object. Using corrector maps generated from system characterization by ice-water phantom measurement completed in the previous project phase, GNL bias correction was performed for test ADC measurements from an independent DWI phantom (room temperature agar) at two offset locations in the bore. The precomputed three-dimensional GNL correctors were retrospectively applied to test DWI scans by the central analysis site. The correction was blinded to reference DWI of the agar phantom at magnet isocenter where the GNL bias is negligible. The performance was evaluated from changes in ADC region of interest histogram statistics before and after correction with respect to the unbiased reference ADC values provided by sites. Both absolute error and nonuniformity of the ADC map induced by GNL (median, 12%; range, -35% to +10%) were substantially reduced by correction (7-fold in median and 3-fold in range). The residual ADC nonuniformity errors were attributed to measurement noise and other non-GNL sources. Correction of systematic GNL bias resulted in a 2-fold decrease in technical variability across scanners (down to site temperature range). The described validation of GNL bias correction marks progress toward implementation of this technology in multicenter trials that utilize quantitative DWI.

QIN DAWG Validation of Gradient Nonlinearity Bias Correction Workflow for Quantitative Diffusion-Weighted Imaging in Multicenter Trials

PubMed Central

Malyarenko, Dariya I.; Wilmes, Lisa J.; Arlinghaus, Lori R.; Jacobs, Michael A.; Huang, Wei; Helmer, Karl G.; Taouli, Bachir; Yankeelov, Thomas E.; Newitt, David; Chenevert, Thomas L.

2017-01-01

Previous research has shown that system-dependent gradient nonlinearity (GNL) introduces a significant spatial bias (nonuniformity) in apparent diffusion coefficient (ADC) maps. Here, the feasibility of centralized retrospective system-specific correction of GNL bias for quantitative diffusion-weighted imaging (DWI) in multisite clinical trials is demonstrated across diverse scanners independent of the scanned object. Using corrector maps generated from system characterization by ice-water phantom measurement completed in the previous project phase, GNL bias correction was performed for test ADC measurements from an independent DWI phantom (room temperature agar) at two offset locations in the bore. The precomputed three-dimensional GNL correctors were retrospectively applied to test DWI scans by the central analysis site. The correction was blinded to reference DWI of the agar phantom at magnet isocenter where the GNL bias is negligible. The performance was evaluated from changes in ADC region of interest histogram statistics before and after correction with respect to the unbiased reference ADC values provided by sites. Both absolute error and nonuniformity of the ADC map induced by GNL (median, 12%; range, −35% to +10%) were substantially reduced by correction (7-fold in median and 3-fold in range). The residual ADC nonuniformity errors were attributed to measurement noise and other non-GNL sources. Correction of systematic GNL bias resulted in a 2-fold decrease in technical variability across scanners (down to site temperature range). The described validation of GNL bias correction marks progress toward implementation of this technology in multicenter trials that utilize quantitative DWI. PMID:28105469

Role of apparent diffusion coefficients with diffusion-weighted magnetic resonance imaging in differentiating between benign and malignant bone tumors.

PubMed

Wang, Tingting; Wu, Xiangru; Cui, Yanfen; Chu, Caiting; Ren, Gang; Li, Wenhua

2014-11-29

Benign and malignant bone tumors can present similar imaging features. This study aims to evaluate the significance of apparent diffusion coefficients (ADC) in differentiating between benign and malignant bone tumors. A total of 187 patients with 198 bone masses underwent diffusion-weighted (DW) magnetic resonance (MR) imaging. The ADC values in the solid components of the bone masses were assessed. Statistical differences between the mean ADC values in the different tumor types were determined by Student's t-test. Histological analysis showed that 84/198 (42.4%) of the bone masses were benign and 114/198 (57.6%) were malignant. There was a significant difference between the mean ADC values in the benign and malignant bone lesions (P<0.05). However, no significant difference was found in the mean ADC value between non-ossifying fibromas, osteofibrous dysplasia, and malignant bone tumors. When an ADC cutoff value≥1.10×10(-3) mm2/s was applied, malignant bone lesions were excluded with a sensitivity of 89.7%, a specificity of 84.5%, a positive predictive value of 82.6%, and a negative predictive value of 95.3%. The combination of DW imaging with ADC quantification and T2-weighted signal characteristics of the solid components in lesions can facilitate differentiation between benign and malignant bone tumors.

Development of a computerized monitoring program to identify narcotic diversion in a pediatric anesthesia practice.

PubMed

Brenn, B Randall; Kim, Margaret A; Hilmas, Elora

2015-08-15

Development of an operational reporting dashboard designed to correlate data from multiple sources to help detect potential drug diversion by automated dispensing cabinet (ADC) users is described. A commercial business intelligence platform was used to create a dashboard tool for rapid detection of unusual patterns of ADC transactions by anesthesia service providers at a large pediatric hospital. By linking information from the hospital's pharmacy information management system (PIMS) and anesthesia information management system (AIMS) in an associative data model, the "narcotic reconciliation dashboard" can generate various reports to help spot outlier activity associated with ADC dispensing of controlled substances and documentation of medication waste processing. The dashboard's utility was evaluated by "back-testing" the program with historical data on an actual episode of diversion by an anesthesia provider that had not been detected through traditional methods of PIMS and AIMS data monitoring. Dashboard-generated reports on key metrics (e.g., ADC transaction counts, discrepancies in dispensed versus reconciled amounts of narcotics, PIMS-AIMS documentation mismatches) over various time frames during the period of known diversion clearly indicated the diverter's outlier status relative to other authorized ADC users. A dashboard program for correlating ADC transaction data with pharmacy and patient care data may be an effective tool for detecting patterns of ADC use that suggest drug diversion. Copyright © 2015 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

Putrescine Is Involved in Arabidopsis Freezing Tolerance and Cold Acclimation by Regulating Abscisic Acid Levels in Response to Low Temperature1

PubMed Central

Cuevas, Juan C.; López-Cobollo, Rosa; Alcázar, Rubén; Zarza, Xavier; Koncz, Csaba; Altabella, Teresa; Salinas, Julio; Tiburcio, Antonio F.; Ferrando, Alejandro

2008-01-01

The levels of endogenous polyamines have been shown to increase in plant cells challenged with low temperature; however, the functions of polyamines in the regulation of cold stress responses are unknown. Here, we show that the accumulation of putrescine under cold stress is essential for proper cold acclimation and survival at freezing temperatures because Arabidopsis (Arabidopsis thaliana) mutants defective in putrescine biosynthesis (adc1, adc2) display reduced freezing tolerance compared to wild-type plants. Genes ADC1 and ADC2 show different transcriptional profiles upon cold treatment; however, they show similar and redundant contributions to cold responses in terms of putrescine accumulation kinetics and freezing sensitivity. Our data also demonstrate that detrimental consequences of putrescine depletion during cold stress are due, at least in part, to alterations in the levels of abscisic acid (ABA). Reduced expression of NCED3, a key gene involved in ABA biosynthesis, and down-regulation of ABA-regulated genes are detected in both adc1 and adc2 mutant plants under cold stress. Complementation analysis of adc mutants with ABA and reciprocal complementation tests of the aba2-3 mutant with putrescine support the conclusion that putrescine controls the levels of ABA in response to low temperature by modulating ABA biosynthesis and gene expression. PMID:18701673

Diffusion-weighted magnetic resonance imaging in monitoring rectal cancer response to neoadjuvant chemoradiotherapy.

PubMed

Barbaro, Brunella; Vitale, Renata; Valentini, Vincenzo; Illuminati, Sonia; Vecchio, Fabio M; Rizzo, Gianluca; Gambacorta, Maria Antonietta; Coco, Claudio; Crucitti, Antonio; Persiani, Roberto; Sofo, Luigi; Bonomo, Lorenzo

2012-06-01

To prospectively monitor the response in patients with locally advanced nonmucinous rectal cancer after chemoradiotherapy (CRT) using diffusion-weighted magnetic resonance imaging. The histopathologic finding was the reference standard. The institutional review board approved the present study. A total of 62 patients (43 men and 19 women; mean age, 64 years; range, 28-83) provided informed consent. T(2)- and diffusion-weighted magnetic resonance imaging scans (b value, 0 and 1,000 mm(2)/s) were acquired before, during (mean 12 days), and 6-8 weeks after CRT. We compared the median apparent diffusion coefficients (ADCs) between responders and nonresponders and examined the associations with the Mandard tumor regression grade (TRG). The postoperative nodal status (ypN) was evaluated. The Mann-Whitney/Wilcoxon two-sample test was used to evaluate the relationships among the pretherapy ADCs, extramural vascular invasion, early percentage of increases in ADCs, and preoperative ADCs. Low pretreatment ADCs (<1.0 × 10(-3)mm(2)/s) were correlated with TRG 4 scores (p = .0011) and associated to extramural vascular invasion with ypN+ (85.7% positive predictive value for ypN+). During treatment, the mean percentage of increase in tumor ADC was significantly greater in the responders than in the nonresponders (p < .0001) and a >23% ADC increase had a 96.3% negative predictive value for TRG 4. In 9 of 16 complete responders, CRT-related tumor downsizing prevented ADC evaluations. The preoperative ADCs were significantly different (p = .0012) between the patients with and without downstaging (preoperative ADC ≥1.4 × 10(-3)mm(2)/s showed a positive and negative predictive value of 78.9% and 61.8%, respectively, for response assessment). The TRG 1 and TRG 2-4 groups were not significantly different. Diffusion-weighted magnetic resonance imaging seems to be a promising tool for monitoring the response to CRT. Copyright © 2012 Elsevier Inc. All rights reserved.

Diffusion-Weighted Magnetic Resonance Imaging in Monitoring Rectal Cancer Response to Neoadjuvant Chemoradiotherapy

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

Barbaro, Brunella, E-mail: bbarbaro@rm.unicatt.it; Vitale, Renata; Valentini, Vincenzo

2012-06-01

Purpose: To prospectively monitor the response in patients with locally advanced nonmucinous rectal cancer after chemoradiotherapy (CRT) using diffusion-weighted magnetic resonance imaging. The histopathologic finding was the reference standard. Methods and Materials: The institutional review board approved the present study. A total of 62 patients (43 men and 19 women; mean age, 64 years; range, 28-83) provided informed consent. T{sub 2}- and diffusion-weighted magnetic resonance imaging scans (b value, 0 and 1,000 mm{sup 2}/s) were acquired before, during (mean 12 days), and 6-8 weeks after CRT. We compared the median apparent diffusion coefficients (ADCs) between responders and nonresponders and examinedmore » the associations with the Mandard tumor regression grade (TRG). The postoperative nodal status (ypN) was evaluated. The Mann-Whitney/Wilcoxon two-sample test was used to evaluate the relationships among the pretherapy ADCs, extramural vascular invasion, early percentage of increases in ADCs, and preoperative ADCs. Results: Low pretreatment ADCs (<1.0 Multiplication-Sign 10{sup -3}mm{sup 2}/s) were correlated with TRG 4 scores (p = .0011) and associated to extramural vascular invasion with ypN+ (85.7% positive predictive value for ypN+). During treatment, the mean percentage of increase in tumor ADC was significantly greater in the responders than in the nonresponders (p < .0001) and a >23% ADC increase had a 96.3% negative predictive value for TRG 4. In 9 of 16 complete responders, CRT-related tumor downsizing prevented ADC evaluations. The preoperative ADCs were significantly different (p = .0012) between the patients with and without downstaging (preoperative ADC {>=}1.4 Multiplication-Sign 10{sup -3}mm{sup 2}/s showed a positive and negative predictive value of 78.9% and 61.8%, respectively, for response assessment). The TRG 1 and TRG 2-4 groups were not significantly different. Conclusion: Diffusion-weighted magnetic resonance imaging seems to be a promising tool for monitoring the response to CRT.« less

Utility of Diffusion-Weighted MRI to Detect Changes in Liver Diffusion in Benign and Malignant Distal Bile Duct Obstruction: The Influence of Choice of b-Values.

PubMed

Karan, Belgin; Erbay, Gurcan; Koc, Zafer; Pourbagher, Aysin; Yildirim, Sedat; Agildere, Ahmet Muhtesem

2016-11-01

The study sought to evaluate the potential of diffusion-weighted magnetic resonance imaging to detect changes in liver diffusion in benign and malignant distal bile duct obstruction and to investigate the effect of the choice of b-values on apparent diffusion coefficient (ADC). Diffusion-weighted imaging was acquired with b-values of 200, 600, 800, and 1000 s/mm 2 . ADC values were obtained in 4 segments of the liver. The mean ADC values of 16 patients with malignant distal bile duct obstruction, 14 patients with benign distal bile duct obstruction, and a control group of 16 healthy patients were compared. Mean ADC values for 4 liver segments were lower in the malignant obstruction group than in the benign obstruction and control groups using b = 200 s/mm 2 (P < .05). Mean ADC values of the left lobe medial and lateral segments were lower in the malignant obstruction group than in the benign obstructive and control groups using b = 600 s/mm 2 (P < .05). Mean ADC values of the right lobe posterior segment were lower in the malignant and benign obstruction groups than in the control group using b = 1000 s/mm 2 (P < .05). Using b = 800 s/mm 2 , ADC values of all 4 liver segments in each group were not significantly different (P > .05). There were no correlations between the ADC values of liver segments and liver function tests. Measurement of ADC shows good potential for detecting changes in liver diffusion in patients with distal bile duct obstruction. Calculated ADC values were affected by the choice of b-values. Copyright © 2016 Canadian Association of Radiologists. Published by Elsevier Inc. All rights reserved.

Attitude Determination and Control Subsystem (ADCS) Preparations for the EPOXI Flyby of Comet Haley 2

NASA Technical Reports Server (NTRS)

Luna, Michael E.; Collins, Stephen M.

2011-01-01

On November 4, 2010 the already "in-flight" Deep Impact spacecraft flew within 700km of comet 103P/Hartley 2 as part of its extended mission EPOXI, the 5th time to date any spacecraft visited a comet. In 2005, the spacecraft had previously imaged a probe impact comet Tempel 1. The EPOXI flyby marked the first time in history that two comets were explored with the same instruments on a re-used spacecraft-with hardware and software originally designed and optimized for a different mission. This made the function of the attitude determination and control subsystem (ADCS) critical to the successful execution of the EPOXI flyby. As part of the spacecraft team preparations, the ADCS team had to perform thorough sequence reviews, key spacecraft activities and onboard calibrations. These activities included: review of background sequences for the initial conditions vector, sun sensor coefficients, and reaction wheel assembly (RWA) de-saturations; design and execution of 10 trajectory correction maneuvers; science calibration of the two telescope instruments; a flight demonstration of the fastest turns conducted by the spacecraft between Earth and comet point; and assessment of RWA health (given RWA problems on other spacecraft).

Reconfigurable radio receiver with fractional sample rate converter and multi-rate ADC based on LO-derived sampling clock

NASA Astrophysics Data System (ADS)

Park, Sungkyung; Park, Chester Sungchung

2018-03-01

A composite radio receiver back-end and digital front-end, made up of a delta-sigma analogue-to-digital converter (ADC) with a high-speed low-noise sampling clock generator, and a fractional sample rate converter (FSRC), is proposed and designed for a multi-mode reconfigurable radio. The proposed radio receiver architecture contributes to saving the chip area and thus lowering the design cost. To enable inter-radio access technology handover and ultimately software-defined radio reception, a reconfigurable radio receiver consisting of a multi-rate ADC with its sampling clock derived from a local oscillator, followed by a rate-adjustable FSRC for decimation, is designed. Clock phase noise and timing jitter are examined to support the effectiveness of the proposed radio receiver. A FSRC is modelled and simulated with a cubic polynomial interpolator based on Lagrange method, and its spectral-domain view is examined in order to verify its effect on aliasing, nonlinearity and signal-to-noise ratio, giving insight into the design of the decimation chain. The sampling clock path and the radio receiver back-end data path are designed in a 90-nm CMOS process technology with 1.2V supply.

Age, period, and cohort analysis of regular dental care behavior and edentulism: A marginal approach

PubMed Central

2011-01-01

Background To analyze the regular dental care behavior and prevalence of edentulism in adult Danes, reported in sequential cross-sectional oral health surveys by the application of a marginal approach to consider the possible clustering effect of birth cohorts. Methods Data from four sequential cross-sectional surveys of non-institutionalized Danes conducted from 1975-2005 comprising 4330 respondents aged 15+ years in 9 birth cohorts were analyzed. The key study variables were seeking dental care on an annual basis (ADC) and edentulism. For the analysis of ADC, survey year, age, gender, socio-economic status (SES) group, denture-wearing, and school dental care (SDC) during childhood were considered. For the analysis of edentulism, only respondents aged 35+ years were included. Survey year, age, gender, SES group, ADC, and SDC during childhood were considered as the independent factors. To take into account the clustering effect of birth cohorts, marginal logistic regressions with an independent correlation structure in generalized estimating equations (GEE) were carried out, with PROC GENMOD in SAS software. Results The overall proportion of people seeking ADC increased from 58.8% in 1975 to 86.7% in 2005, while for respondents aged 35 years or older, the overall prevalence of edentulism (35+ years) decreased from 36.4% in 1975 to 5.0% in 2005. Females, respondents in the higher SES group, in more recent survey years, with no denture, and receiving SDC in all grades during childhood were associated with higher probability of seeking ADC regularly (P < 0.05). The interaction of SDC and age (P < 0.0001) was significant. The probabilities of seeking ADC were even higher among subjects with SDC in all grades and aged 45 years or older. Females, older age group, respondents in earlier survey years, not seeking ADC, lower SES group, and not receiving SDC in all grades were associated with higher probability of being edentulous (P < 0.05). Conclusions With the use of GEE, the potential clustering effect of birth cohorts in sequential cross-sectional oral health survey data could be appropriately considered. The success of Danish dental health policy was demonstrated by a continued increase of regular dental visiting habits and tooth retention in adults because school dental care was provided to Danes in their childhood. PMID:21410991

Correlation of ADC value with pathologic indexes in colorectal tumor homografts in Balb/c mouse.

PubMed

Li, Xiaojun; Jiang, Hongnan; Niu, Jinliang; Zheng, Ying

2014-08-01

Noninvasive diffusion-weighted magnetic resonance imaging (DWI) is a well-studied MR imaging technique for quantifying water diffusion especially in tumor area. The correlation between apparent diffusion coefficient (ADC) value and apoptosis or proliferation is not clear by now. This study aimed to investigate whether DWI-ADC value could be used as an imaging marker related with pathologic indexes of tumors. A total of 30 Balb/c mice with HT29 colorectal carcinoma were subjected to DWI and histologic analysis. The percentage of ADC changes and the apoptotic and proliferating indexes were calculated at predefined time points. Kolmogorov-Smirnov distances were considered to determine whether the percentage of ADC changes, and the apoptotic and proliferating indexes were normally distributed. An independent-samples t-test was used to analyze the difference between apoptotic and proliferating indexes in the two groups. THERE WAS A STATISTICALLY SIGNIFICANT DIFFERENCE IN PROLIFERATING INDEX BETWEEN THE RADIOTHERAPY AND CONTROL GROUPS (MEAN PROLIFERATING INDEX: 49.27% vs. 83.09%), and there was a statistically significant difference in apoptotic index between the two groups (mean apoptotic index: 37.7% vs. 2.71%). A significant positive correlation was found between the percentage of ADC changes of the viable tissue and apoptotic index. Pearson's correlation coefficient was 0.655 (P=0.015). A significant negative correlation was found between the percentage of ADC changes of the viable tissue and ki-67 proliferation index. Pearson's correlation coefficient was 0.734 (P<0.001). Our results suggest that ADC value may be used in measurement of cell apoptotic and proliferating indexes in colorectal carcinoma.

Pancreatic neuroendocrine tumour: Correlation of apparent diffusion coefficient or WHO classification with recurrence-free survival.

PubMed

Kim, Mimi; Kang, Tae Wook; Kim, Young Kon; Kim, Seong Hyun; Kwon, Wooil; Ha, Sang Yun; Ji, Sang A

2016-03-01

To evaluate the correlation between grade of pancreatic neuroendocrine tumours (pNETs) based on the 2010 World Health Organization (WHO) classification and the apparent diffusion coefficient (ADC), and to assess whether the ADC value and WHO classification can predict recurrence-free survival (RFS) after surgery for pNETs. This retrospective study was approved by the Institutional Review Board. The requirement for informed consent was waived. Between March 2009 and November 2014, forty-nine patients who underwent magnetic resonance (MR) imaging with diffusion-weighted image and subsequent surgery for single pNETs were included. Correlations among qualitative MR imaging findings, quantitative ADC values, and WHO classifications were assessed. An ordered logistic regression test was used to control for tumour size as a confounding factor. The association between ADC value (or WHO classification) and RFS was analysed. All tumors (n=49) were classified as low- (n=29, grade 1), intermediate- (n=17, grade 2), and high-grade (n=3, grade 3), respectively. The mean ADC of pNETs was moderately negatively correlated with WHO classification before and after adjustment for tumour size (ρ=-0.64, p<0.001 and ρ=-0.55, p=0.001 respectively). RFS was significantly associated with WHO classification (p=0.007), but not with the ADC value (p=0.569). The ADC value of pNETs is moderately correlated with WHO tumour grade, regardless of tumour size. However, the WHO tumour classification of pNET may be more suitable for predicting RFS than the ADC value. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Development of COTS ADC SEE Test System for the ATLAS LArCalorimeter Upgrade

DOE PAGES

Hu, Xue -Ye; Chen, Hu -Cheng; Chen, Kai; ...

2014-12-01

Radiation-tolerant, high speed, high density and low power commercial off-the-shelf (COTS) analog-to-digital converters (ADCs) are planned to be used in the upgrade to the Liquid Argon (LAr) calorimeter front end (FE) trigger readout electronics. Total ionization dose (TID) and single event effect (SEE) are two important radiation effects which need to be characterized on COTS ADCs. In our initial TID test, Texas Instruments (TI) ADS5272 was identified to be the top performer after screening a total 17 COTS ADCs from different manufacturers with dynamic range and sampling rate meeting the requirements of the FE electronics. Another interesting feature of ADS5272more » is its 6.5 clock cycles latency, which is the shortest among the 17 candidates. Based on the TID performance, we have designed a SEE evaluation system for ADS5272, which allows us to further assess its radiation tolerance. In this paper, we present a detailed design of ADS5272 SEE evaluation system and show the effectiveness of this system while evaluating ADS5272 SEE characteristics in multiple irradiation tests. According to TID and SEE test results, ADS5272 was chosen to be implemented in the full-size LAr Trigger Digitizer Board (LTDB) demonstrator, which will be installed on ATLAS calorimeter during the 2014 Long Shutdown 1 (LS1).« less

Diffusion weighted MRI and 18F-FDG PET/CT in non-small cell lung cancer (NSCLC): does the apparent diffusion coefficient (ADC) correlate with tracer uptake (SUV)?

PubMed

Regier, M; Derlin, T; Schwarz, D; Laqmani, A; Henes, F O; Groth, M; Buhk, J-H; Kooijman, H; Adam, G

2012-10-01

To investigate the potential correlation of the apparent diffusion coefficient assessed by diffusion-weighted MRI (DWI) and glucose metabolism determined by the standardized uptake value (SUV) at 18F-FDG PET/CT in non-small cell lung cancer (NSCLC). 18F-FDG PET/CT and DWI (TR/TE, 2000/66 ms; b-values, 0 and 500 s/mm(2)) were performed in 41 consecutive patients with histologically verified NSCLC. Analysing the PET-CT data calculation of the mean (SUV(mean)) and maximum (SUV(max)) SUV was performed. By placing a region-of-interest (ROI) encovering the entire tumor mean (ADC(mean)) and minimum ADC (ADC(min)) were determined by two independent radiologists. Results of 18F-FDG PET-CT and DWI were compared on a per-patient basis. For statistical analysis Pearson's correlation coefficient, Bland-Altman and regression analysis were assessed. Data analysis revealed a significant inverse correlation of the ADC(min) and SUV(max) (r=-0.46; p=0.032). Testing the correlation of the ADC(min) and SUV(max) for each histological subtype separately revealed that the inverse correlation was good for both adenocarcinomas (r=-0.47; p=0.03) and squamouscell carcinomas (r=-0.71; p=0.002), respectively. No significant correlation was found for the comparison of ADC(min) and SUV(mean) (r=-0.29; p=0.27), ADC(mean) vs. SUV(mean) (r=-0.28; p=0.31) or ADC(mean) vs. SUV(max) (r=-0.33; p=0.23). The κ-value of 0.88 indicated a good agreement between both observers. This preliminary study is the first to verify the relation between the SUV and the ADC in NSCLC. The significant inverse correlation of these two quantitative imaging approaches points out the association of metabolic activity and tumor cellularity. Therefore, DWI with ADC measurement might represent a new prognostic marker in NSCLC. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

WE-G-18C-02: Estimation of Optimal B-Value Set for Obtaining Apparent Diffusion Coefficient Free From Perfusion in Non-Small Cell Lung Cancer

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

Karki, K; Hugo, G; Ford, J

2014-06-15

Purpose: Diffusion-weighted MRI (DW-MRI) is increasingly being investigated for radiotherapy planning and response assessment. Selection of a limited number of b-values in DW-MRI is important to keep geometrical variations low and imaging time short. We investigated various b-value sets to determine an optimal set for obtaining monoexponential apparent diffusion coefficient (ADC) close to perfusion-insensitive intravoxel incoherent motion (IVIM) model ADC (ADC IVIM) in nonsmall cell lung cancer. Methods: Seven patients had 27 DW-MRI scans before and during radiotherapy in a 1.5T scanner. Respiratory triggering was applied to the echo-planar DW-MRI with TR=4500ms approximately, TE=74ms, pixel size=1.98X1.98mm{sub 2}, slice thickness=4–6mm andmore » 7 axial slices. Diffusion gradients were applied to all three axes producing traceweighted images with eight b-values of 0–1000μs/μm{sup 2}. Monoexponential model ADC values using various b-value sets were compared to ADC IVIM using all b-values. To compare the relative noise in ADC maps, intra-scan coefficient of variation (CV) of active tumor volumes was computed. Results: ADC IVIM, perfusion coefficient and perfusion fraction for tumor volumes were in the range of 880-1622 μm{sup 2}/s, 8119-33834 μm{sup 2}/s and 0.104–0.349, respectively. ADC values using sets of 250, 800 and 1000; 250, 650 and 1000; and 250–1000μs/μm{sup 2} only were not significantly different from ADC IVIM(p>0.05, paired t-test). Error in ADC values for 0–1000, 50–1000, 100–1000, 250–1000, 500–1000, and three b-value sets- 250, 500 and 1000; 250, 650 and 1000; and 250, 800 and 1000μs/μm{sup 2} were 15.0, 9.4, 5.6, 1.4, 11.7, 3.7, 2.0 and 0.2% relative to the reference-standard ADC IVIM, respectively. Mean intrascan CV was 20.2, 20.9, 21.9, 24.9, 32.6, 25.8, 25.4 and 24.8%, respectively, whereas that for ADC IVIM was 23.3%. Conclusion: ADC values of two 3 b-value sets (250, 650 and 1000; and 250, 800 and 1000μs/μm{sup 2}) approached ADC IVIM, with relative noise comparable to that of ADC IVIM. These sets may be used to obtain perfusion-insensitive ADC values in lung tumors. E. Weiss: Funding through Varian Medical Systems and Philips Oncology Systems, UpToDate royalties. G. Hugo: NIH R01CA166119, P01 CA116602, NHMRC Project Grant.« less

GNSS software receiver sampling noise and clock jitter performance and impact analysis

NASA Astrophysics Data System (ADS)

Chen, Jian Yun; Feng, XuZhe; Li, XianBin; Wu, GuangYao

2015-02-01

In the design of a multi-frequency multi-constellation GNSS software defined radio receivers is becoming more and more popular due to its simple architecture, flexible configuration and good coherence in multi-frequency signal processing. It plays an important role in navigation signal processing and signal quality monitoring. In particular, GNSS software defined radio receivers driving the sampling clock of analogue-to-digital converter (ADC) by FPGA implies that a more flexible radio transceiver design is possible. According to the concept of software defined radio (SDR), the ideal is to digitize as close to the antenna as possible. Whereas the carrier frequency of GNSS signal is of the frequency of GHz, converting at this frequency is expensive and consumes more power. Band sampling method is a cheaper, more effective alternative. When using band sampling method, it is possible to sample a RF signal at twice the bandwidth of the signal. Unfortunately, as the other side of the coin, the introduction of SDR concept and band sampling method induce negative influence on the performance of the GNSS receivers. ADC's suffer larger sampling clock jitter generated by FPGA; and low sampling frequency introduces more noise to the receiver. Then the influence of sampling noise cannot be neglected. The paper analyzes the sampling noise, presents its influence on the carrier noise ratio, and derives the ranging error by calculating the synchronization error of the delay locked loop. Simulations aiming at each impact factors of sampling-noise-induced ranging error are performed. Simulation and experiment results show that if the target ranging accuracy is at the level of centimeter, the quantization length should be no less than 8 and the sampling clock jitter should not exceed 30ps.

Characterization of testicular germ cell tumors: Whole-lesion histogram analysis of the apparent diffusion coefficient at 3T.

PubMed

Min, Xiangde; Feng, Zhaoyan; Wang, Liang; Cai, Jie; Yan, Xu; Li, Basen; Ke, Zan; Zhang, Peipei; You, Huijuan

2018-01-01

To assess the values of parameters derived from whole-lesion histograms of the apparent diffusion coefficient (ADC) at 3T for the characterization of testicular germ cell tumors (TGCTs). A total of 24 men with TGCTs underwent 3T diffusion-weighted imaging. Fourteen tumors were pathologically confirmed as seminomas, and ten tumors were pathologically confirmed as nonseminomas. Whole-lesion histogram analysis of the ADC values was performed. A Mann-Whitney U test was employed to compare the differences in ADC histogram parameters between seminomas and nonseminomas. Receiver operating characteristic analysis was used to identify the cutoff values for each parameter for differentiating seminomas from nonseminomas; furthermore, the area under the curve (AUC) was calculated to evaluate the diagnostic accuracy. The median of 10th, 25th, 50th, 75th, and 90th percentiles and mean, minimum and maximum ADC values were all significantly reduced for seminomas compared with nonseminomas (p<0.05 for all). In contrast, the median of kurtosis and skewness of ADC values of seminomas were both significantly increased compared with those of nonseminomas (p=0.003 and 0.001, respectively). For differentiating nonseminomas from seminomas, the 10th percentile ADC yielded the highest AUC with a sensitivity and specificity of 100% and 92.86%, respectively. Whole-lesion histogram analysis of ADCs might be used for preoperative characterization of TGCTs. Copyright © 2017 Elsevier B.V. All rights reserved.

Comparison and reproducibility of ADC measurements in breathhold, respiratory triggered, and free-breathing diffusion-weighted MR imaging of the liver.

PubMed

Kwee, Thomas C; Takahara, Taro; Koh, Dow-Mu; Nievelstein, Rutger A J; Luijten, Peter R

2008-11-01

To compare and determine the reproducibility of apparent diffusion coefficient (ADC) measurements of the normal liver parenchyma in breathhold, respiratory triggered, and free-breathing diffusion-weighted magnetic resonance imaging (DWI). Eleven healthy volunteers underwent three series of DWI. Each DWI series consisted of one breathhold, one respiratory triggered, and two free-breathing (thick and thin slice acquisition) scans of the liver, at b-values of 0 and 500 s/mm2. ADCs of the liver parenchyma were compared by using nonparametric tests. Reproducibility was assessed by the Bland-Altman method. Mean ADCs (in 10(-3) mm2/sec) in respiratory triggered DWI (2.07-2.27) were significantly higher than mean ADCs in breathhold DWI (1.57-1.62), thick slice free-breathing DWI (1.62-1.65), and thin slice free-breathing DWI (1.57-1.66) (P<0.005). Ranges of mean difference in ADC measurement+/-limits of agreement between two scans were -0.02-0.05+/-0.16-0.24 in breathhold DWI, -0.14-0.20+/-0.59-0.60 in respiratory triggered DWI, -0.03-0.03+/-0.20-0.29 in thick slice free-breathing DWI, and -0.01-0.09+/-0.21-0.29 in thin slice free-breathing DWI. ADC measurements of the normal liver parenchyma in respiratory triggered DWI are significantly higher and less reproducible than in breathhold and free-breathing DWI. Copyright (c) 2008 Wiley-Liss, Inc.

Whole-lesion histogram analysis metrics of the apparent diffusion coefficient as a marker of breast lesions characterization at 1.5 T.

PubMed

Bougias, H; Ghiatas, A; Priovolos, D; Veliou, K; Christou, A

2017-05-01

To retrospectively assess the role of whole-lesion apparent diffusion coefficient (ADC) in the characterization of breast tumors by comparing different histogram metrics. 49 patients with 53 breast lesions underwent magnetic resonance imaging (MRI). ADC histogram parameters, including the mean, mode, 10th/50th/90th percentile, skewness, kurtosis, and entropy ADCs, were derived for the whole-lesion volume in each patient. Mann-Whitney U-test, area under the receiver-operating characteristic curve (AUC) were used for statistical analysis. The mean, mode and 10th/50th/90th percentile ADC values were significantly lower in malignant lesions compared with benign ones (all P < 0.0001), while skewness was significantly higher in malignant lesions P = 0.02. However, no significant difference was found between entropy and kurtosis values in malignant lesions compared with benign ones (P = 0.06 and P = 1.00, respectively). Univariate logistic regression showed that 10th and 50th percentile ADC yielded the highest AUC (0.985; 95% confidence interval [CI]: 0.902, 1.000 and 0.982; 95% confidence interval [CI]: 0.896, 1.000 respectively), whereas kurtosis value yielded the lowest AUC (0.500; 95% CI: 0.355, 0.645), indicating that 10th and 50th percentile ADC values may be more accurate for lesion discrimination. Whole-lesion ADC histogram analysis could be a helpful index in the characterization and differentiation between benign and malignant breast lesions with the 10th and 50th percentile ADC be the most accurate discriminators. Copyright © 2017 The College of Radiographers. Published by Elsevier Ltd. All rights reserved.

Diffusion-weighted imaging for the cellularity assessment and matrix characterization of soft tissue tumour.

PubMed

Robba, Tiziana; Chianca, Vito; Albano, Domenico; Clementi, Valeria; Piana, Raimondo; Linari, Alessandra; Comandone, Alessandro; Regis, Guido; Stratta, Maurizio; Faletti, Carlo; Borrè, Alda

2017-11-01

To evaluate whether apparent diffusion coefficient (ADC) of diffusion-weighted imaging (DWI) is able to investigate the histological features of soft tissue tumours. We reviewed MRIs of soft tissue tumours performed from 2012 to 2015 to calculate the average ADCs. We included 46 patients (27 male; mean age: 57 years, range 12-85 years) with histologically proven soft tissue tumours (10 benign, 2 intermediate 34 malignant) grouped into eight tumour type classes. An experienced pathologist assigned a semi-quantitative cellularity score (very high, high, medium and low) and tumour grading. The t test, ANOVA and linear regression were used to correlate ADC with clinicopathological data. Approximate receiver operating characteristic curves were created to predict possible uses of ADC to differentiate benign from malignant tumours. There was a significant difference (p < 0.01) in ADCs between these three groups excluding myxoid sarcomas. A significant difference was also evident between the tumour type classes (p < 0.001), grade II and III myxoid lesions (p < 0.05), tumour grading classes (p < 0.001) and cellularity scores classes (p < 0.001), with the lowest ADCs in the very high cellularity. While the linear regression analysis showed a significant relationship between ADC and tumour cellularity (r = 0.590, p ≤ 0.05) and grading (r = 0.437, p ≤ 0.05), no significant relationship was found with age, gender, tumour size and histological subtype. An optimal cut-off ADC value of 1.45 × 10 -3 mm 2 /s with 76.8% accuracy was found to differentiate benign from malignant tumours. DWI may offer adjunctive information about soft tissue tumours, but its clinical role is still to be defined.

Diffusion-Weighted Magnetic Resonance Imaging Early After Chemoradiotherapy to Monitor Treatment Response in Head-and-Neck Squamous Cell Carcinoma

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

Vandecaveye, Vincent, E-mail: Vincent.Vandecaveye@uzleuven.be; Dirix, Piet; De Keyzer, Frederik

2012-03-01

Purpose: To evaluate diffusion-weighted imaging (DWI) for assessment of treatment response in head and neck squamous cell carcinoma (HNSCC) three weeks after the end of chemoradiotherapy (CRT). Methods and Materials: Twenty-nine patients with HNSCC underwent magnetic resonance imaging (MRI) prior to and 3 weeks after CRT, including T{sub 2}-weighted and pre- and postcontrast T{sub 1}-weighted sequences and an echo-planar DWI sequence with six b values (0 to 1,000 s/mm{sup 2}), from which the apparent diffusion coefficient (ADC) was calculated. ADC changes 3 weeks posttreatment compared to baseline ( Increment ADC) between responding and nonresponding primary lesions and adenopathies were correlatedmore » with 2 years locoregional control and compared with a Mann-Whitney test. In a blinded manner, the Increment ADC was compared to conventional MRI 3 weeks post-CRT and the routinely implemented CT, on average 3 months post-CRT, which used size-related and morphological criteria. Positive and negative predictive values (PPV and NPV, respectively) were compared between the Increment ADC and anatomical imaging. Results: The Increment ADC of lesions with later tumor recurrence was significantly lower than lesions with complete remission for both primary lesions (-2.3% {+-} 0.3% vs. 80% {+-} 41%; p < 0.0001) and adenopathies (19.9% {+-} 32% vs. 63% {+-} 36%; p = 0.003). The Increment ADC showed a PPV of 89% and an NPV of 100% for primary lesions and a PPV of 70% and an NPV of 96% for adenopathies per neck side. DWI improved PPV and NPV compared to anatomical imaging. Conclusion: DWI with the Increment ADC 3 weeks after concluding CRT for HNSCC allows for early assessment of treatment response.« less

Indeterminate orbital masses: restricted diffusion at MR imaging with echo-planar diffusion-weighted imaging predicts malignancy.

PubMed

Sepahdari, Ali R; Aakalu, Vinay K; Setabutr, Pete; Shiehmorteza, Masoud; Naheedy, John H; Mafee, Mahmood F

2010-08-01

To determine whether magnetic resonance (MR) imaging with diffusion-weighted (DW) imaging can help discriminate between radiologically indeterminate benign and malignant orbital masses and to identify optimal apparent diffusion coefficient (ADC) thresholds for such discrimination. Informed consent was waived for this HIPAA-compliant institutional review board-approved retrospective study. Forty-seven orbital masses imaged with echo-planar DW imaging were identified in 47 patients (25 female patients, 22 male patients; average age, 35 years). A fellowship-trained orbital surgeon determined reference-standard diagnoses on the basis of chart review, and a neuroradiology fellow and senior neuroradiologist who were blinded to the diagnoses selected a region of interest for each lesion by consensus. ADC was calculated from signal intensity on DW images obtained with b = 1000 and b = 0 sec/mm(2). Lesion ADC was also compared with that of normal-appearing white matter (ADC ratio). The Student t test was used to compare groups. Receiver operating characteristic analysis was performed. Intraobserver agreement was assessed with a repeat data collection. Malignant lesions had lower ADCs than benign lesions, irrespective of patient age (P < .02) and in adults specifically (P < .05). Lymphomas had lower ADCs than pseudotumors (P < .001). An ADC of less than 1.0 x 10(-3) mm(2)/sec and an ADC ratio of less than 1.2 were optimal for predicting malignancy (sensitivity, 63% for both; specificity, 84% and 90%, respectively; and accuracy, 77% and 81%, respectively). Lymphoma was differentiated from pseudotumor with 100% accuracy (in 16 of 16 cases) by using these values. Infiltrative lesions that were hypointense on T2-weighted images were better characterized with DW imaging than lesions that were hyperintense or well defined. Echo-planar DW MR imaging can help characterize indeterminate orbital masses.

Role of Arginine decarboxylase (ADC) in Arabidopsis thaliana defence against the pathogenic bacterium Pseudomonas viridiflava.

PubMed

Rossi, F R; Marina, M; Pieckenstain, F L

2015-07-01

Polyamine biosynthesis starts with putrescine production through the decarboxylation of arginine or ornithine. In Arabidopsis thaliana, putrescine is synthesised exclusively by arginine decarboxylase (ADC), which exists as two isoforms (ADC1 and 2) that are differentially regulated by abiotic stimuli, but their role in defence against pathogens has not been studied in depth. This work analysed the participation of ADC in Arabidopsis defence against Pseudomonas viridiflava. ADC activity and expression, polyamine levels and bacterial resistance were analysed in null mutants of each ADC isoform. In non-infected wild-type (WT) plants, ADC2 expression was much higher than ADC1. Analysis of adc mutants demonstrated that ADC2 contributes to a much higher extent than ADC1 to basal ADC activity and putrescine biosynthesis. In addition, adc2 mutants showed increased basal expression of salicylic acid- and jasmonic acid-dependent PR genes. Bacterial infection induced putrescine accumulation and ADC1 expression in WT plants, but pathogen-induced putrescine accumulation was blocked in adc1 mutants. Results suggest a specific participation of ADC1 in defence, although basal resistance was not decreased by dysfunction of either of the two ADC genes. In addition, and as opposed to WT plants, bacterial infection increased ADC2 expression and ADC activity in adc1 mutants, which could counterbalance the lack of ADC1. Results demonstrate a major contribution of ADC2 to total ADC activity and the specific induction of ADC1 in response to infection. A certain degree of functional redundancy between the two isoforms in relation to their contribution to basal resistance is also evident. © 2015 German Botanical Society and The Royal Botanical Society of the Netherlands.

Design and demonstration of an advanced data collection/position location system

NASA Technical Reports Server (NTRS)

1977-01-01

The final report on a breadboard evaluation and demonstration program is reported concerning the applicability of MSK modulation and chirp-z transformer technology in Advanced Data Collection/Position Location (ADC/PL) systems. The program effort consisted of three phases - design, testing, and evaluation. Section 2 describes the breadboard hardware built during the design phase of the program, Section 3 describes the tests conducted on the breadboard and the results of the tests, and Section 4 presents a brief analysis and summary of the findings of the breadboard tests and develops a sample ADC/PL system which incorporates both MSK modulation and a chirp-z transformer.

Converting the Active Digital Controller for Use in Two Tests

NASA Technical Reports Server (NTRS)

Wright, Robert G.

1995-01-01

The Active Digital Controller is a system used to control the various functions of wind tunnel models. It has the capability of digitizing and saving of up to sixty-four channels of analog data. It can output up to 16 channels of analog command signals. In addition to its use as a general controller, it can run up to two distinct control laws. All of this is done at a regulated speed of two hundred hertz. The Active Digital Controller (ADC) was modified for use in the Actively Controlled Response of Buffet Affected Tails (ACROBAT) tests and for side-wall pressure data acquisition. The changes included general maintenance and updating of the controller as well as setting up special modes of operation. The ACROBAT tests required that two sets of output signals be available. The pressure data acquisition needed a sampling rate of four hundred hertz, twice the standard ADC rate. These modifications were carried out and the ADC was used during the ACROBAT wind tunnel entry.

"Smart" Sensor Module

NASA Technical Reports Server (NTRS)

Mahajan, Ajay

2007-01-01

An assembly that contains a sensor, sensor-signal-conditioning circuitry, a sensor-readout analog-to-digital converter (ADC), data-storage circuitry, and a microprocessor that runs special-purpose software and communicates with one or more external computer(s) has been developed as a prototype of "smart" sensor modules for monitoring the integrity and functionality (the "health") of engineering systems. Although these modules are now being designed specifically for use on rocket-engine test stands, it is anticipated that they could also readily be designed to be incorporated into health-monitoring subsystems of such diverse engineering systems as spacecraft, aircraft, land vehicles, bridges, buildings, power plants, oilrigs, and defense installations. The figure is a simplified block diagram of the "smart" sensor module. The analog sensor readout signal is processed by the ADC, the digital output of which is fed to the microprocessor. By means of a standard RS-232 cable, the microprocessor is connected to a local personal computer (PC), from which software is downloaded into a randomaccess memory in the microprocessor. The local PC is also used to debug the software. Once the software is running, the local PC is disconnected and the module is controlled by, and all output data from the module are collected by, a remote PC via an Ethernet bus. Several smart sensor modules like this one could be connected to the same Ethernet bus and controlled by the single remote PC. The software running in the microprocessor includes driver programs for operation of the sensor, programs that implement self-assessment algorithms, programs that implement protocols for communication with the external computer( s), and programs that implement evolutionary methodologies to enable the module to improve its performance over time. The design of the module and of the health-monitoring system of which it is a part reflects the understanding that the main purpose of a health-monitoring system is to detect damage and, therefore, the health-monitoring system must be able to function effectively in the presence of damage and should be capable of distinguishing between damage to itself and damage to the system being monitored. A major benefit afforded by the self-assessment algorithms is that in the output of the module, the sensor data indicative of the health of the engineering system being monitored are coupled with a confidence factor that quantifies the degree of reliability of the data. Hence, the output includes information on the health of the sensor module itself in addition to information on the health of the engineering system being monitored.

[Brain apparent diffusion coefficient: differences caused by age, sex, laterality, and distinct b value].

PubMed

García Santos, J M; Ordóñez González, C; Torres del Río, S

2009-01-01

To analyze the effects of age, sex, and b value on the apparent diffusion coefficient (ADC) in brain areas affected by neurodegenerative diseases. We studied the ADC of the genu and splenium of the corpus callosum and of the hippocampus in normal patients using diffusion magnetic resonance imaging (dMRI) with b1,000 s/mm2 and b3,000 s/mm2. We calculated the differences between the ADC (diffusion differential [DD]) with b1,000 and with b3,000 for each region. Patients were classified into the following age groups (60 years old). We used a Kruskal-Wallis one-way ANOVA and the Bonferroni correction to analyze the differences in ADC and DD between age groups and between sexes. Pearson's chi-square test was used to correlate the ADC and DD with age. In the right hippocampus, we observed differences in ADC (b1,000, p=0.011; b3,000, p=0.024) and DD (p=0.006) with age. Differences in ADC were observed between the 31-60 year-old age group and the >60 year-old age group (p=0.009) for b1,000, and between the<30 year-old age group and the 31-60 year-old age group (p=0.036) for b3,000. The DD in the >60 year-old age group was different from the rest. In the corpus callosum, there were significant differences between sexes in the DD of the genu (p=0.016). The DD was correlated with age in the right hippocampus (r=0.321, p=0.023). Our data indicate greater stability in mean ADC values with b3000 during aging. It might be useful to analyze the ADC with a higher b in patients with neurodegenerative diseases.

Differentiation between cavernous hemangiomas and untreated malignant neoplasms of the liver with free-breathing diffusion-weighted MR imaging: comparison with T2-weighted fast spin-echo MR imaging.

PubMed

Soyer, Philippe; Corno, Lucie; Boudiaf, Mourad; Aout, Mounir; Sirol, Marc; Placé, Vinciane; Duchat, Florent; Guerrache, Youcef; Fargeaudou, Yann; Vicaut, Eric; Pocard, Marc; Hamzi, Lounis

2011-11-01

To test interobserver variability of ADC measurements and compare the diagnostic performances of free-breathing diffusion-weighted (FBDW) with that of T2-weighted FSE (T2WFSE) MR imaging for differentiating between cavernous hemangiomas and untreated malignant hepatic neoplasms. Thirty-five patients with cavernous hemangiomas and 35 with untreated hepatic malignant neoplasms had FBDW and T2WFSE MR imaging. Hepatic lesions were characterized with ADC measurement and visual evaluation. Interobserver agreement for ADC measurement was calculated. Association between ADC value and lesion type was assessed using univariate analysis. Sensitivity, specificity and accuracy of ADC values and visual evaluation of MR images for the diagnosis of untreated malignant hepatic neoplasm were compared. ADC measurements showed excellent interobserver correlation (intraclass correlation coefficient=0.980). Malignant neoplasms had lower ADC values than hemangiomas for the two observers (1.11×10(-3) mm2/s±.21×10(-3) vs. 1.77×10(-3) mm2/s±.29×10(-3) for observer 1 and 1.11×10(-3) mm2/s±.19×10(-3) vs. 1.79×10(-3) mm2/s±.32×10(-3) for observer 2) and univariate analysis found significant correlations between lesion type and ADC values. Depending on ADC threshold value, accuracy for the diagnosis of malignant neoplasm varied from 82.9% to 94.3%. Using visual evaluation, FBDW showed better specificity and accuracy than T2WFSE MR images for the diagnosis of malignant neoplasm (97.1% vs. 77.1% and 94.3% vs. 62.9%, respectively). FBDW imaging provides reproducible quantitative information and surpasses the value of T2WFSE MR imaging for differentiating between cavernous hemangiomas and untreated malignant hepatic neoplasms. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Comparative study with two different enrichments in the culture media used in the disinfectant efficacy assay.

PubMed

Sabagh, Bruna Peres; Souto, Aline da Silva Soares; Reis, Louise Moreira; Silva, Sérgio Alves da; Pereira, Daniella Cristina Rodrigues; Neves, Marta de Campos; Pinheiro, Rodrigo Rollin; Duarte, Rafael Silva; Miyazaki, Neide Hiromi Tokumaru; Bôas, Maria Helena Simões Villas

2012-02-01

Recent changes in Brazilian legislation for commercial disinfectants have been published due to the recent epidemic of nosocomial infections caused by rapidly growing mycobacteria (RGM) in many states of Brazil over the last 8years. One of these documents requires that all the manufacturers provide evidence of efficacy of sterilizing and disinfectant products, used for semi critical medical devices, against the Mycobacterium bovis BCG Moreau and Mycobacterium abscessus subsp. bolletii INCQS 00594 strains by using the Confirmative in vitro Test for Determining Tuberculocidal Activity of Disinfectants recommended by the Association of Official Analytical Chemists. These changes have caused additional costs and increased problems for importation of enrichment products at national laboratories where disinfectant efficacy assay service is performed. Middlebrook ADC Enrichment (ADC) is provided by a unique manufacturer and used in the official protocol. The aim of the present study was to evaluate an alternative in house low-cost enrichment composed of fetal bovine serum and glucose (FBSG) with ADC for performance of disinfectant efficacy assay against mycobacteria. After obtaining the growth curves for M. abscessus ATCC 19977, M. abscessus subsp. bolletii INCQS 00594, Mycobacterium chelonae ATCC 35752, and Mycobacterium fortuitum ATCC 6841 by using ADC enrichment and FBSG in Kirchners and 7H9 culture media. Through statistical analysis via the Kruskal-Wallis test on the evaluation of microorganism growth rate, it was observed that there was no inhibition of RGM growth by any of the enrichments used. These results suggest that low-cost enrichment FBSG may be used as a potential substitute of ADC for composition of media for mycobacterial growth, including in disinfectant tests. Copyright © 2011 Elsevier B.V. All rights reserved.

Signaling protein signature predicts clinical outcome of non-small-cell lung cancer.

PubMed

Jin, Bao-Feng; Yang, Fan; Ying, Xiao-Min; Gong, Lin; Hu, Shuo-Feng; Zhao, Qing; Liao, Yi-Da; Chen, Ke-Zhong; Li, Teng; Tai, Yan-Hong; Cao, Yuan; Li, Xiao; Huang, Yan; Zhan, Xiao-Yan; Qin, Xuan-He; Wu, Jin; Chen, Shuai; Guo, Sai-Sai; Zhang, Yu-Cheng; Chen, Jing; Shen, Dan-Hua; Sun, Kun-Kun; Chen, Lu; Li, Wei-Hua; Li, Ai-Ling; Wang, Na; Xia, Qing; Wang, Jun; Zhou, Tao

2018-03-06

Non-small-cell lung cancer (NSCLC) is characterized by abnormalities of numerous signaling proteins that play pivotal roles in cancer development and progression. Many of these proteins have been reported to be correlated with clinical outcomes of NSCLC. However, none of them could provide adequate accuracy of prognosis prediction in clinical application. A total of 384 resected NSCLC specimens from two hospitals in Beijing (BJ) and Chongqing (CQ) were collected. Using immunohistochemistry (IHC) staining on stored formalin-fixed paraffin-embedded (FFPE) surgical samples, we examined the expression levels of 75 critical proteins on BJ samples. Random forest algorithm (RFA) and support vector machines (SVM) computation were applied to identify protein signatures on 2/3 randomly assigned BJ samples. The identified signatures were tested on the remaining BJ samples, and were further validated with CQ independent cohort. A 6-protein signature for adenocarcinoma (ADC) and a 5-protein signature for squamous cell carcinoma (SCC) were identified from training sets and tested in testing sets. In independent validation with CQ cohort, patients can also be divided into high- and low-risk groups with significantly different median overall survivals by Kaplan-Meier analysis, both in ADC (31 months vs. 87 months, HR 2.81; P <  0.001) and SCC patients (27 months vs. not reached, HR 9.97; P <  0.001). Cox regression analysis showed that both signatures are independent prognostic indicators and outperformed TNM staging (ADC: adjusted HR 3.07 vs. 2.43, SCC: adjusted HR 7.84 vs. 2.24). Particularly, we found that only the ADC patients in high-risk group significantly benefited from adjuvant chemotherapy (P = 0.018). Both ADC and SCC protein signatures could effectively stratify the prognosis of NSCLC patients, and may support patient selection for adjuvant chemotherapy.

Cost effective, high performance transient recorder systems, utilizing the latest ADC`s, S/H`s, memories and PLA`s; Final report, May 14, 1987--February 14, 1990

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

Joerger, F. A.

1990-02-01

This project was to develop five transient recorder modules of various speeds and features. Four of the modules; TR200, 200MHZ recorder; TR2/25, Dual 25MHZ recorder; TR1012, 10MHZ, 12 bit recorder, and the ADC3216, 32 channel, 16 bit recorder were developed in the international CAMAC standard. The fifth unit, VTR1, 25MHZ recorder was packaged in the VME standard. Three of the modules, Models TR200, TR2/25 and VTR1 are already in Phase 3. The ADC3216 has been prototyped and successfully evaluated by a number of customers. The last module, Model TR1012, has been completely designed and the artwork completed. This module willmore » undergo tests shortly. 4 figs.« less

First time combination of frozen density embedding theory with the algebraic diagrammatic construction scheme for the polarization propagator of second order

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

Prager, Stefan, E-mail: stefan.prager@iwr.uni-heidelberg.de; Dreuw, Andreas, E-mail: dreuw@uni-heidelberg.de; Zech, Alexander, E-mail: alexander.zech@unige.ch

The combination of Frozen Density Embedding Theory (FDET) and the Algebraic Diagrammatic Construction (ADC) scheme for the polarization propagator for describing environmental effects on electronically excited states is presented. Two different ways of interfacing and expressing the so-called embedding operator are introduced. The resulting excited states are compared with supermolecular calculations of the total system at the ADC(2) level of theory. Molecular test systems were chosen to investigate molecule–environment interactions of varying strength from dispersion interaction up to multiple hydrogen bonds. The overall difference between the supermolecular and the FDE-ADC calculations in excitation energies is lower than 0.09 eV (max)more » and 0.032 eV in average, which is well below the intrinsic error of the ADC(2) method itself.« less

Biochemical and Structural Analysis of Inhibitors Targeting the ADC-7 Cephalosporinase of Acinetobacter baumannii

DOE PAGES

Powers, Rachel A.; Swanson, Hollister C.; Taracila, Magdalena A.; ...

2014-11-07

β-Lactam resistance in Acinetobacter baumannii presents one of the greatest challenges to contemporary antimicrobial chemotherapy. Much of this resistance to cephalosporins derives from the expression of the class C β-lactamase enzymes, known as Acinetobacter-derived cephalosporinases (ADCs). Currently, β-lactamase inhibitors are structurally similar to β-lactam substrates and are not effective inactivators of this class C cephalosporinase. Herein, two boronic acid transition state inhibitors (BATSIs S02030 and SM23) that are chemically distinct from β-lactams were designed and tested for inhibition of ADC enzymes. BATSIs SM23 and S02030 bind with high affinity to ADC-7, a chromosomal cephalosporinase from Acinetobacter baumannii (K i =more » 21.1 ± 1.9 nM and 44.5 ± 2.2 nM, respectively). The X-ray crystal structures of ADC-7 were determined in both the apo form (1.73 Å resolution) and in complex with S02030 (2.0 Å resolution). In the complex, S02030 makes several canonical interactions: the O1 oxygen of S02030 is bound in the oxyanion hole, and the R1 amide group makes key interactions with conserved residues Asn152 and Gln120. In addition, the carboxylate group of the inhibitor is meant to mimic the C 3/C 4 carboxylate found in β-lactams. The C 3/C 4 carboxylate recognition site in class C enzymes is comprised of Asn346 and Arg349 (AmpC numbering), and these residues are conserved in ADC-7. Interestingly, in the ADC-7/S02030 complex, the inhibitor carboxylate group is observed to interact with Arg340, a residue that distinguishes ADC-7 from the related class C enzyme AmpC. A thermodynamic analysis suggests that ΔH driven compounds may be optimized to generate new lead agents. In conclusion, the ADC-7/BATSI complex provides insight into recognition of non-β-lactam inhibitors by ADC enzymes and offers a starting point for the structure-based optimization of this class of novel β-lactamase inhibitors against a key resistance target.« less

Fast response neutron emission monitor for fusion reactor using stilbene scintillator and Flash-ADC.

PubMed

Itoga, T; Ishikawa, M; Baba, M; Okuji, T; Oishi, T; Nakhostin, M; Nishitani, T

2007-01-01

The stilbene neutron detector which has been used for neutron emission profile monitoring in JT-60U has been improved, to respond to the requirement to observe the high-frequency phenomena in megahertz region such as toroidicity-induced Alfvén Eigen mode in burning plasma as well as the spatial profile and the energy spectrum. This high-frequency phenomenon is of great interest and one of the key issues in plasma physics in recent years. To achieve a fast response in the stilbene detector, a Flash-ADC is applied and the wave form of the anode signal stored directly, and neutron/gamma discrimination was carried out via software with a new scheme for data acquisition mode to extend the count rate limit to MHz region from 1.3 x 10(5) neutron/s in the past, and confirmed the adequacy of the method.

A look-up-table digital predistortion technique for high-voltage power amplifiers in ultrasonic applications.

PubMed

Gao, Zheng; Gui, Ping

2012-07-01

In this paper, we present a digital predistortion technique to improve the linearity and power efficiency of a high-voltage class-AB power amplifier (PA) for ultrasound transmitters. The system is composed of a digital-to-analog converter (DAC), an analog-to-digital converter (ADC), and a field-programmable gate array (FPGA) in which the digital predistortion (DPD) algorithm is implemented. The DPD algorithm updates the error, which is the difference between the ideal signal and the attenuated distorted output signal, in the look-up table (LUT) memory during each cycle of a sinusoidal signal using the least-mean-square (LMS) algorithm. On the next signal cycle, the error data are used to equalize the signal with negative harmonic components to cancel the amplifier's nonlinear response. The algorithm also includes a linear interpolation method applied to the windowed sinusoidal signals for the B-mode and Doppler modes. The measurement test bench uses an arbitrary function generator as the DAC to generate the input signal, an oscilloscope as the ADC to capture the output waveform, and software to implement the DPD algorithm. The measurement results show that the proposed system is able to reduce the second-order harmonic distortion (HD2) by 20 dB and the third-order harmonic distortion (HD3) by 14.5 dB, while at the same time improving the power efficiency by 18%.

[Comparative study on clinical and pathological changes of liver fibrosis with diffusion-weighted imaging].

PubMed

Zhou, Mei-Ling; Yan, Fu-Hua; Xu, Peng-Ju; Chen, Cai-Zhong; Shen, Ji-Zhang; Li, Ren-Chen; Ji, Yuan; Shi, Jian-Ying

2009-07-07

To evaluate the clinical practical value of apparent diffusion coefficient (ADC) measurements based on diffusion-weighted MR imaging (DWI) for quantification of liver fibrosis and inflammation for hepatitis viral infection. Diffusion-weighted MRI with parallel imaging was prospectively performed on 85 patients with chronic hepatitis and on 22 healthy volunteers within a single breath-hold using a single-shot spin-echo echo-planar sequence at b values of 100, 300, 500, 800 and 1000 s/mm2 respectively. ADC values of liver were measured with five different b values. The inflammation grades and fibrosis stages were evaluated histologically by biopsy. One-way analysis of variance and Spearman' s rank correlation test were used for statistical analysis. Receiver operating characteristics analysis was used to assess the performance of ADC in predicting the presence of stage > or = 2 and stage > or = 3 hepatic fibrosis, and grade > or = 1 hepatic inflammation. There was moderate negative correlation between hepatic ADC values and fibrosis stage. And the best correlation was obtained for a b value of 800 s/mm2 (r = -0.697, P = 0. 000). At all b values there was a significant decrease in hepatic ADC in patients with stage < or = 1 versus stage > or = 2 fibrosis and stage < or = 2 versus stage > or = 3 fibrosis (P < 0.05). Hepatic ADC was a significant predictor of stage > or = 2 and > or = 3 fibrosis. The areas under the curve were 0.909 vs 0.917, sensitivity 76.6% vs 80.0% and specificity 88.3% vs 91.5% (ADC with a b value of 800 s/mm2, 1.26 x 10(-3) mm2/s or less and 1.19 x 10(-3) mm2/s or less). There was weak to moderate negative correlation between ADCs and inflammation grade. Hepatic ADC was a significant predictor of grade > 1 inflammation with an area under the curve of 0.781, sensitivity of 60.0% and specificity of 86.4% (ADC with a b value of 500 s/mm2, 1.54 x 10(-3) mm2/s or less). The DWI measurement of hepatic ADC can be used to quantify liver fibrosis and inflammation. It will be a new approach for early diagnosis and therapeutic follow-up of hepatic fibrosis.

NASA Tech Briefs, July 2003

NASA Technical Reports Server (NTRS)

2003-01-01

Topics covered include: Real-Time, High-Frequency QRS Electrocardiograph; Software for Improved Extraction of Data From Tape Storage; Radio System for Locating Emergency Workers; Software for Displaying High-Frequency Test Data; Capacitor-Chain Successive-Approximation ADC; Simpler Alternative to an Optimum FQPSK-B Viterbi Receiver; Multilayer Patch Antenna Surrounded by a Metallic Wall; Software To Secure Distributed Propulsion Simulations; Explicit Pore Pressure Material Model in Carbon-Cloth Phenolic; Meshed-Pumpkin Super-Pressure Balloon Design; Corrosion Inhibitors as Penetrant Dyes for Radiography; Transparent Metal-Salt-Filled Polymeric Radiation Shields; Lightweight Energy Absorbers for Blast Containers; Brush-Wheel Samplers for Planetary Exploration; Dry Process for Making Polyimide/ Carbon-and-Boron-Fiber Tape; Relatively Inexpensive Rapid Prototyping of Small Parts; Magnetic Field Would Reduce Electron Backstreaming in Ion Thrusters; Alternative Electrochemical Systems for Ozonation of Water; Interferometer for Measuring Displacement to Within 20 pm; UV-Enhanced IR Raman System for Identifying Biohazards; Prognostics Methodology for Complex Systems; Algorithms for Haptic Rendering of 3D Objects; Modeling and Control of Aerothermoelastic Effects; Processing Digital Imagery to Enhance Perceptions of Realism; Analysis of Designs of Space Laboratories; Shields for Enhanced Protection Against High-Speed Debris; Study of Dislocation-Ordered In(x)Ga(1-x)As/GaAs Quantum Dots; and Tilt-Sensitivity Analysis for Space Telescopes.

Utility of DWI with quantitative ADC values in ovarian tumors: a meta-analysis of diagnostic test performance.

PubMed

Pi, Shan; Cao, Rong; Qiang, Jin Wei; Guo, Yan Hui

2018-01-01

Background Diffusion-weighted imaging (DWI) and quantitative apparent diffusion coefficient (ADC) values are widely used in the differential diagnosis of ovarian tumors. Purpose To assess the diagnostic performance of quantitative ADC values in ovarian tumors. Material and Methods PubMed, Embase, the Cochrane Library, and local databases were searched for studies assessing ovarian tumors using quantitative ADC values. We quantitatively analyzed the diagnostic performances for two clinical problems: benign vs. malignant tumors and borderline vs. malignant tumors. We evaluated diagnostic performances by the pooled sensitivity and specificity values and by summary receiver operating characteristic (SROC) curves. Subgroup analyses were used to analyze study heterogeneity. Results From the 742 studies identified in the search results, 16 studies met our inclusion criteria. A total of ten studies evaluated malignant vs. benign ovarian tumors and six studies assessed malignant vs. borderline ovarian tumors. Regarding the diagnostic accuracy of quantitative ADC values for distinguishing between malignant and benign ovarian tumors, the pooled sensitivity and specificity values were 0.91 and 0.91, respectively. The area under the SROC curve (AUC) was 0.96. For differentiating borderline from malignant tumors, the pooled sensitivity and specificity values were 0.89 and 0.79, and the AUC was 0.91. The methodological quality of the included studies was moderate. Conclusion Quantitative ADC values could serve as useful preoperative markers for predicting the nature of ovarian tumors. Nevertheless, prospective trials focused on standardized imaging parameters are needed to evaluate the clinical value of quantitative ADC values in ovarian tumors.

Using the apparent diffusion coefficient to identifying MGMT promoter methylation status early in glioblastoma: importance of analytical method

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

Rundle-Thiele, Dayle; Day, Bryan; Stringer, Brett

Accurate knowledge of O{sup 6}-methylguanine methyltransferase (MGMT) gene promoter subtype in patients with glioblastoma (GBM) is important for treatment. However, this test is not always available. Pre-operative diffusion MRI (dMRI) can be used to probe tumour biology using the apparent diffusion coefficient (ADC); however, its ability to act as a surrogate to predict MGMT status has shown mixed results. We investigated whether this was due to variations in the method used to analyse ADC. We undertook a retrospective study of 32 patients with GBM who had MGMT status measured. Matching pre-operative MRI data were used to calculate the ADC withinmore » contrast enhancing regions of tumour. The relationship between ADC and MGMT was examined using two published ADC methods. A strong trend between a measure of ‘minimum ADC’ and methylation status was seen. An elevated minimum ADC was more likely in the methylated compared to the unmethylated MGMT group (U = 56, P = 0.0561). In contrast, utilising a two-mixture model histogram approach, a significant reduction in mean measure of the ‘low ADC’ component within the histogram was associated with an MGMT promoter methylation subtype (P < 0.0246). This study shows that within the same patient cohort, the method selected to analyse ADC measures has a significant bearing on the use of that metric as a surrogate marker of MGMT status. Thus for dMRI data to be clinically useful, consistent methods of data analysis need to be established prior to establishing any relationship with genetic or epigenetic profiling.« less

Liver diffusivity in healthy volunteers and patients with chronic liver disease: Comparison of breath-hold and free-breathing techniques

PubMed Central

Eatesam, Mamak; Noworolski, Susan M; Tien, Phyllis C; Nystrom, Michelle; Dodge, Jennifer L.; Merriman, Raphael B.; Qayyum, Aliya

2011-01-01

Purpose To compare liver ADC obtained with breath-hold and free-breathing diffusion weighted imaging (DWI) in healthy volunteers and patients with liver disease. Materials and Methods Twenty-eight subjects, 12 healthy volunteers and 16 patients (9 NAFLD, 7 chronic active HCV), underwent breath-hold (BH) and free-breathing (FB) DWI MRI at 1.5T. Pearson’s correlation coefficient was used to determine correlation while paired t-tests assessed differences between BH and FB ADC. Estimated bias was calculated using the Bland-Altman method. Results Liver ADC (×10−3 mm2/sec) was lower on BH for all groups (mean difference 0.36±0.20; p<0.01). ADC was higher in healthy volunteers (BH 1.80±0.18; FB 2.24±0.20) compared to NAFLD patients (BH 1.43±0.27; FB 1.78±0.28) (p<0.001) and HCV patients (BH 1.63±0.191; FB 1.88±0.12). Overall correlation between BH and FB ADC was (r =0.75), greatest in NAFLD (r =0.90) compared to the correlation in HCV (r =0.24) and healthy subjects (r =0.34). Bland-Altman plots did not show agreement in mean absolute difference and estimated bias between subjects. Conclusion Correlation between BH and FB liver ADC is moderate indicating that BH and FB should not be used interchangeably. Additionally, the lower ADC values in BH versus FB should be accounted for when comparing different liver DWI studies. PMID:22034200

Liver diffusivity in healthy volunteers and patients with chronic liver disease: comparison of breathhold and free-breathing techniques.

PubMed

Eatesam, Mamak; Noworolski, Susan M; Tien, Phyllis C; Nystrom, Michelle; Dodge, Jennifer L; Merriman, Raphael B; Qayyum, Aliya

2012-01-01

To compare liver ADC obtained with breathhold and free-breathing diffusion weighted imaging (DWI) in healthy volunteers and patients with liver disease. Twenty-eight subjects, 12 healthy volunteers and 16 patients (9 NAFLD, 7 chronic active HCV), underwent breathhold (BH) and free-breathing (FB) DWI MRI at 1.5 Tesla. Pearson's correlation coefficient was used to determine correlation while paired t-tests assessed differences between BH and FB ADC. Estimated bias was calculated using the Bland-Altman method. Liver ADC (×10(-3) mm(2) /s) was lower on BH for all groups (mean difference 0.36 ± 0.20; P < 0.01). ADC was higher in healthy volunteers (BH 1.80 ± 0.18; FB 2.24 ± 0.20) compared with NAFLD patients (BH 1.43 ± 0.27; FB 1.78 ± 0.28) (P < 0.001) and HCV patients (BH 1.63 ± 0.191; FB 1.88 ± 0.12). Overall correlation between BH and FB ADC was (r = 0.75), greatest in NAFLD (r = 0.90) compared with the correlation in HCV (r = 0.24) and healthy subjects (r = 0.34). Bland-Altman plots did not show agreement in mean absolute difference and estimated bias between subjects. Correlation between BH and FB liver ADC is moderate indicating that BH and FB should not be used interchangeably. Additionally, the lower ADC values in BH versus FB should be accounted for when comparing different liver DWI studies. Copyright © 2011 Wiley-Liss, Inc.

Accuracy of apparent diffusion coefficient value measurement on PACS workstation: A comparative analysis.

PubMed

El Kady, Reem M; Choudhary, Arabinda Kumar; Tappouni, Rafel

2011-03-01

The purpose of this article is to evaluate the accuracy of apparent diffusion coefficient (ADC) measurements made with a PACS workstation compared with measurements made with a dedicated workstation, which is currently considered the reference standard. A retrospective review was performed in liver lesions from 79 patients using three MRI platforms. The final diagnosis was established by liver biopsy in 31 patients and by dynamic MRI and follow-up, both clinical and radiologic as indicated, in 48 patients. Each lesion that was clearly demonstrable on the ADC map was measured with a commercial dedicated postprocessing workstation and again with a PACS system. A two-sample t test was used to determine the statistically significant differences between the two ADC measurements. A total of 79 patients with 120 liver lesions were included. ADC values measured on the workstation were 0.4-4.38 × 10(-3) mm(2)/s. The ADC values measured on the PACS were 0.42-4.35 × 10(-3) mm(2)/s. The T value was -1.113, with 119 degrees of freedom, and the significance level was 0.268, which implies no significant difference between the two different measuring systems for all pathologic abnormalities and MRI scanners used. ADC values measured on a routine PACS workstation are as accurate as the values obtained on a dedicated specialized workstation. ADC value measurement on the routine PACS will save time and lead to increased utilization, which, in turn, will lead to an improved understanding of the different disease processes and their clinical management.

Differential role of gene hypermethylation in adenocarcinomas, squamous cell carcinomas and cervical intraepithelial lesions of the uterine cervix.

PubMed

Blanco-Luquin, Idoia; Guarch, Rosa; Ojer, Amaya; Pérez-Janices, Noemí; Martín-Sánchez, Esperanza; Maria-Ruiz, Sergio; Monreal-Santesteban, Iñaki; Blanco-Fernandez, Laura; Pernaut-Leza, Eduardo; Escors, David; Guerrero-Setas, David

2015-09-01

Cervical cancer is the third most common cancer in women worldwide. The hypermethylation of P16, TSLC-1 and TSP-1 genes was analyzed in squamous cell carcinomas (SCC), cervical intraepithelial lesions (CIN) and adenocarcinomas (ADC) of the uterine cervix (total 181 lesions). Additionally human papillomavirus (HPV) type, EPB41L3, RASSF1 and RASSF2 hypermethylation were tested in ADC and the results were compared with those obtained previously by our group in SCC. P16, TSLC-1 and TSP-1 hypermethylation was more frequent in SCCs than in CINs. These percentages and the corresponding ones for EPB41L3, RASSF1 and RASSF2 genes were also higher in SCCs than in ADCs, except for P16. The presence of HPV in ADCs was lower than reported previously in SCC and CIN. Patients with RASSF1A hypermethylation showed significantly longer disease-free survival (P = 0.015) and overall survival periods (P = 0.009) in ADC patients. To our knowledge, this is the first description of the EPB41L3 and RASSF2 hypermethylation in ADCs. These results suggest that the involvement of DNA hypermethylation in cervical cancer varies depending on the histological type, which might contribute to explaining the different prognosis of patients with these types of tumors. © 2015 Japanese Society of Pathology and Wiley Publishing Asia Pty Ltd.

Can diffusion-weighted imaging distinguish between benign and malignant pediatric liver tumors?

PubMed

Caro-Domínguez, Pablo; Gupta, Abha A; Chavhan, Govind B

2018-01-01

There are limited data on utility of diffusion-weighted imaging (DWI) in the evaluation of pediatric liver lesions. To determine whether qualitative and quantitative DWI can be used to differentiate benign and malignant pediatric liver lesions. We retrospectively reviewed MRIs in children with focal liver lesions to qualitatively evaluate lesions noting diffusion restriction, T2 shine-through, increased diffusion, hypointensity on DWI and apparent diffusion coefficient (ADC) maps, and intermediate signal on both, and to measure ADC values. Pathology confirmation or a combination of clinical, laboratory and imaging features, and follow-up was used to determine final diagnosis. We included 112 focal hepatic lesions in 89 children (median age 11.5 years, 51 female), of which 92 lesions were benign and 20 malignant. Interobserver agreement was almost perfect for both qualitative (kappa 0.8735) and quantitative (intraclass correlation coefficient [ICC] 0.96) diffusion assessment. All malignant lesions showed diffusion restriction. Most benign lesions other than abscesses were not restricted. There was significant association of qualitative restriction with malignancy and non-restriction with benignancy (Fisher exact test P<0.0001). Mean normalized ADC values of malignant lesions (1.23x10 -3  mm 2 /s) were lower than benign lesions (1.62x10 -3  mm 2 /s; Student's t-test, P<0.015). However, there was significant overlap of ADC between benign and malignant lesions, with wide range for each diagnosis. Receiver operating characteristic (ROC) analysis revealed an area under the curve (AUC) of 0.63 for predicting malignancy using an ADC cut-off value of ≤1.20x10 -3  mm 2 /s, yielding a sensitivity of 78% and a specificity of 54% for differentiating malignant from benign lesions. Qualitative diffusion restriction in pediatric liver lesions is a good predictor of malignancy and can help to differentiate between benign and malignant lesions, in conjunction with conventional MR sequences. Even though malignant lesions demonstrated significantly lower ADC values than benign lesions, the use of quantitative diffusion remains limited in its utility for distinguishing them because of the significant overlap and wide ranges of ADC values.

Distortion-free diffusion MRI using an MRI-guided Tri-Cobalt 60 radiotherapy system: Sequence verification and preliminary clinical experience.

PubMed

Gao, Yu; Han, Fei; Zhou, Ziwu; Cao, Minsong; Kaprealian, Tania; Kamrava, Mitchell; Wang, Chenyang; Neylon, John; Low, Daniel A; Yang, Yingli; Hu, Peng

2017-10-01

Monitoring tumor response during the course of treatment and adaptively modifying treatment plan based on tumor biological feedback may represent a new paradigm for radiotherapy. Diffusion MRI has shown great promises in assessing and predicting tumor response to radiotherapy. However, the conventional diffusion-weighted single-shot echo-planar-imaging (DW-ssEPI) technique suffers from limited resolution, severe distortion, and possibly inaccurate ADC at low field strength. The purpose of this work was to develop a reliable, accurate and distortion-free diffusion MRI technique that is practicable for longitudinal tumor response evaluation and adaptive radiotherapy on a 0.35 T MRI-guided radiotherapy system. A diffusion-prepared turbo spin echo readout (DP-TSE) sequence was developed and compared with the conventional diffusion-weighted single-shot echo-planar-imaging sequence on a 0.35 T MRI-guided radiotherapy system (ViewRay). A spatial integrity phantom was used to quantitate and compare the geometric accuracy of the two diffusion sequences for three orthogonal orientations. The apparent diffusion coefficient (ADC) accuracy was evaluated on a diffusion phantom under both 0 °C and room temperature to cover a diffusivity range between 0.40 × 10 -3 and 2.10 × 10 -3 mm 2 /s. Ten room temperature measurements repeated on five different days were conducted to assess the ADC reproducibility of DP-TSE. Two glioblastoma (GBM) and six sarcoma patients were included to examine the in vivo feasibility. The target registration error (TRE) was calculated to quantitate the geometric accuracy where structural CT or MR images were co-registered to the diffusion images as references. ADC maps from DP-TSE and DW-ssEPI were calculated and compared. A tube phantom was placed next to patients not treated on ViewRay, and ADCs of this reference tube were also compared. The proposed DP-TSE passed the spatial integrity test (< 1 mm within 100 mm radius and < 2 mm within 175 mm radius) under the three orthogonal orientations. The detected errors were 0.474 ± 0.355 mm, 0.475 ± 0.287 mm, and 0.546 ± 0.336 mm in the axial, coronal, and sagittal plane. DW-ssEPI, however, failed the tests due to severe distortion and low signal intensity. Noise correction must be performed for the DW-ssEPI to avoid ADC quantitation errors, whereas it is optional for DP-TSE. At 0 °C, the two sequences provided accurate quantitation with < 3% variation with the reference. In the room temperature study, discrepancies between ADCs from DP-TSE and the reference were within 4%, but could be as high as 8% for DW-ssEPI after the noise correction. Excellent ADC reproducibility with a coefficient of variation < 5% was observed among the 10 measurements of DP-TSE, indicating desirable robustness for ADC-based tumor response assessment. In vivo TRE in DP-TSE was less than 1.6 mm overall, whereas it could be greater than 12 mm in DW-ssEPI. For GBM patients, the CSF and brain tissue ADCs from DP-TSE were within the ranges found in literature. ADC differences between the two techniques were within 8% among the six sarcoma patients. For the reference tube that had a relatively low diffusivity, the two diffusion sequences provided matched measurements. A diffusion technique with excellent geometric fidelity, accurate, and reproducible ADC measurement was demonstrated for longitudinal tumor response assessment using a low-field MRI-guided radiotherapy system. © 2017 American Association of Physicists in Medicine.

The Preclinical Alzheimer Cognitive Composite

PubMed Central

Donohue, Michael C.; Sperling, Reisa A.; Salmon, David P.; Rentz, Dorene M.; Raman, Rema; Thomas, Ronald G.; Weiner, Michael; Aisen, Paul S.

2015-01-01

IMPORTANCE As Alzheimer disease (AD) research moves to intervene in presymptomatic phases of the disease, we must develop outcome measures sensitive to the earliest disease-related changes. OBJECTIVE To demonstrate the feasibility of a cognitive composite outcome for clinically normal elderly participants with evidence of AD pathology using the ADCS Preclinical Alzheimer Cognitive Composite (ADCS-PACC). The ADCS-PACC combines tests that assess episodic memory, timed executive function, and global cognition. The ADCS-PACC is the primary outcome measure for the first clinical trial in preclinical AD (ie, the Anti-Amyloid Treatment in Asymptomatic Alzheimer’s study). DESIGN, SETTING, AND PARTICIPANTS With the ADCS-PACC, we derive pilot estimates of amyloid-related decline using data from 2 observational studies conducted in North America and another conducted in Australia. The participants analyzed had normal cognition and mean ages of 75.81, 71.37, and 79.42 years across the 3 studies. MAIN OUTCOMES AND MEASURES For the 2 studies that collected data on Aβ levels (ADNI and AIBL), we estimate decline in a preclinical AD “Aβ-positive” placebo group and compare them with an “Aβ-negative” group. For the study that did not include data on Aβ levels (the ADCS Prevention Instrument [ADCS-PI] study), we grouped participants by the presence of APOE-ɛ4 and by clinical progression. RESULTS In ADNI, Aβ-positive participants showed more decline than did Aβ-negative participants with regard to the ADCS-PACC score at 24 months (mean [SE] difference, −1.239 [0.522] [95% CI, −2.263 to −0.215]; P = .02). In AIBL, the mean (SE) difference is significant at both 18 months (−1.009 [0.406] [95% CI, −1.805 to −0.213]; P = .01) and 36 months (−1.404 [0.452] [95% CI, −2.290 to −0.519]; P = .002). In the ADCS-PI study, APOE-ɛ4 allele carriers performed significantly worse on the ADCS-PACC at 24 months (mean [SE] score, −0.742 [0.294] [95% CI, −1.318 to −0.165]; P = .01) and 36 months (−1.531 [0.469] [95% CI, −2.450 to −0.612]; P = .001). In the ADCS-PI study, cognitively normal participants who progress from a global Clinical Dementia Rating score of 0 are significantly worse on the ADCS-PACC than cognitively normal participants who are stable with a global Clinical Dementia Rating score of 0 at months 12, 24, and 36 (mean [SE] ADCS-PACC score, −4.471 [0.702] [95% CI, −5.848 to −3.094]; P < .001). Using pilot estimates of variance and assuming 500 participants per group with 30% attrition and a 5% α level, we project 80% power to detect effects in the range of Δ = 0.467 to 0.733 on the ADCS-PACC. CONCLUSIONS AND RELEVANCE Analyses of at-risk cognitively normal populations suggest that we can reliably measure the first signs of cognitive decline with the ADCS-PACC. These analyses also suggest the feasibility of secondary prevention trials. PMID:24886908

The role of diffusion weighted MR imaging for differentiation between Graves' disease and Hashimoto thyroiditis.

PubMed

Ozturk, T; Bozgeyik, Z; Ozturk, F; Burakgazi, G; Akyol, M; Coskun, S; Ozkan, Y; Ogur, E

2015-08-01

The aim of this study was to evaluate the usefulness of diffusion-weighted magnetic resonance imaging (DWMRI) for differentation between Graves' disease and Hashimoto's thyroiditis. Fifty patients (27 Graves diseases and 23 Hashimoto thyroiditis) and twenty healthy volunteers were examined using T1, T2 and DWMRI. The patients were diagnosed on the basis of physical findings and the results of thyroid function tests and serological tests. Circular ROIs were positioned on the bilateral thyroid lobes and isthmus. All measurements were repeated three different b values including 100, 600 and 1000 s/mm2 in all cases. ADC (Apparent diffusion coefficient) maps were calculated automatically with the MR system. Mean ADC values were 2.93 × 10-3, 1.97 × 10-3 and 1.62 × 10-3 mm2/s in the healthy volunteers; 3.47 × 10-3, 2.25 × 10-3 and 1.64 × 10-3 mm2/s in Graves' disease; 2.53 × 10-3, 1.76 × 10-3, 1.28 × 10-3 mm2/s in Hashimoto thyroiditis for b100, b600 and b1000, respectively. The ADC values of the Graves diseases were higher than healty volunteers and Hashimoto thyroiditis. ADC values were statistically significant for differentation between Hashimoto thyroiditis and Graves' disease all b values (p < 0.05). DWMRI is fast sequence and does not require contrast agent. Quantitative assessment of the lesion is possible using ADC map. So, DWMRI may be useful differentiation of the Hashimoto thyroiditis and Graves' disease.

Whole lesion histogram analysis of meningiomas derived from ADC values. Correlation with several cellularity parameters, proliferation index KI 67, nucleic content, and membrane permeability.

PubMed

Surov, Alexey; Hamerla, Gordian; Meyer, Hans Jonas; Winter, Karsten; Schob, Stefan; Fiedler, Eckhard

2018-09-01

To analyze several histopathological features and their possible correlations with whole lesion histogram analysis derived from ADC maps in meningioma. The retrospective study involved 36 patients with primary meningiomas. For every tumor, the following histogram analysis parameters of apparent diffusion coefficient (ADC) were calculated: ADC mean , ADC max , ADC min , ADC median , ADC mode , ADC percentiles: P10, P25, P75, P90, as well kurtosis, skewness, and entropy. All measures were performed by two radiologists. Proliferation index KI 67, minimal, maximal and mean cell count, total nucleic area, and expression of water channel aquaporin 4 (AQP4) were estimated. Spearman's correlation coefficient was used to analyze associations between investigated parameters. A perfect interobserver agreement for all ADC values (0.84-0.97) was identified. All ADC values correlated inversely with tumor cellularity with the strongest correlation between P10, P25 and mean cell count (-0.558). KI 67 correlated inversely with all ADC values except ADC min . ADC parameters did not correlate with total nucleic area. All ADC values correlated statistically significant with expression of AQP4. ADC histogram analysis is a valid method with an excellent interobserver agreement. Cellularity parameters and proliferation potential are associated with different ADC values. Membrane permeability may play a greater role for water diffusion than cell count and proliferation activity. Copyright © 2018 Elsevier Inc. All rights reserved.

Pre-Clinical and Clinical Evaluation of High Resolution, Mobile Gamma Camera and Positron Imaging Devices

DTIC Science & Technology

2007-11-01

accuracy. FPGA ADC data acquisition is controlled by distributed Java -based software. Java -based server application sits on each of the acquisition...JNI ( Java Native Interface) is used to allow Java indirect control of the USB driver. Fig. 5. Photograph of mobile electronics rack...supplies with the monitor and keyboard. The server application on each of these machines is controlled by a remote client Java -based application

Histogram analysis parameters of apparent diffusion coefficient reflect tumor cellularity and proliferation activity in head and neck squamous cell carcinoma.

PubMed

Surov, Alexey; Meyer, Hans Jonas; Winter, Karsten; Richter, Cindy; Hoehn, Anna-Kathrin

2018-05-04

Our purpose was to analyze associations between apparent diffusion coefficient (ADC) histogram analysis parameters and histopathologicalfeatures in head and neck squamous cell carcinoma (HNSCC). The study involved 32 patients with primary HNSCC. For every tumor, the following histogram analysis parameters were calculated: ADCmean, ADCmax, ADC min , ADC median , ADC mode , P10, P25, P75, P90, kurtosis, skewness, and entropy. Furthermore, proliferation index KI 67, cell count, total and average nucleic areas were estimated. Spearman's correlation coefficient (p) was used to analyze associations between investigated parameters. In overall sample, all ADC values showed moderate inverse correlations with KI 67. All ADC values except ADCmax correlated inversely with tumor cellularity. Slightly correlations were identified between total/average nucleic area and ADC mean , ADC min , ADC median , and P25. In G1/2 tumors, only ADCmode correlated well with Ki67. No statistically significant correlations between ADC parameters and cellularity were found. In G3 tumors, Ki 67 correlated with all ADC parameters except ADCmode. Cell count correlated well with all ADC parameters except ADCmax. Total nucleic area correlated inversely with ADC mean , ADC min , ADC median , P25, and P90. ADC histogram parameters reflect proliferation potential and cellularity in HNSCC. The associations between histopathology and imaging depend on tumor grading.

Longitudinal diffusion MRI for treatment response assessment: Preliminary experience using an MRI-guided tri-cobalt 60 radiotherapy system.

PubMed

Yang, Yingli; Cao, Minsong; Sheng, Ke; Gao, Yu; Chen, Allen; Kamrava, Mitch; Lee, Percy; Agazaryan, Nzhde; Lamb, James; Thomas, David; Low, Daniel; Hu, Peng

2016-03-01

To demonstrate the preliminary feasibility of a longitudinal diffusion magnetic resonance imaging (MRI) strategy for assessing patient response to radiotherapy at 0.35 T using an MRI-guided radiotherapy system (ViewRay). Six patients (three head and neck cancer, three sarcoma) who underwent fractionated radiotherapy were enrolled in this study. A 2D multislice spin echo single-shot echo planar imaging diffusion pulse sequence was implemented on the ViewRay system and tested in phantom studies. The same pulse sequence was used to acquire longitudinal diffusion data (every 2-5 fractions) on the six patients throughout the entire course of radiotherapy. The reproducibility of the apparent diffusion coefficient (ADC) measurements was assessed using reference regions and the temporal variations of the tumor ADC values were evaluated. In diffusion phantom studies, the ADC values measured on the ViewRay system matched well with reference ADC values with <5% error for a range of ground truth diffusion coefficients of 0.4-1.1 × 10(-3) mm(2)/s. The remote reference regions (i.e., brainstem in head and neck patients) had consistent ADC values throughout the therapy for all three head and neck patients, indicating acceptable reproducibility of the diffusion imaging sequence. The tumor ADC values changed throughout therapy, with the change differing between patients, ranging from a 40% drop in ADC within the first week of therapy to gradually increasing throughout therapy. For larger tumors, intratumoral heterogeneity was observed. For one sarcoma patient, postradiotherapy biopsy showed less than 10% necrosis score, which correlated with the observed 40% decrease in ADC from the fifth fraction to the eighth treatment fraction. This pilot study demonstrated that longitudinal diffusion MRI is feasible using the 0.35 T ViewRay MRI. Larger patient cohort studies are warranted to correlate the longitudinal diffusion measurements to patient outcomes. Such an approach may enable response-guided adaptive radiotherapy.

Role of Diffusion-Weighted Magnetic Resonance (MR) Imaging in Differentiation Between Graves’ Disease and Painless Thyroiditis

PubMed Central

Abdel Razek, Ahmed Abdel Khalek; El-Said, Amr Abd El-hamid

2017-01-01

Summary Background To assess the role of diffusion-weighted MR imaging in differentiation between Graves’ disease and painless thyroiditis. Material/Methods A prospective study was conducted among 37 consecutive patients with untreated thyrotoxicosis (25 female and 12 male; mean age of 44 years) and 15 ageand sex-matched controls. Diffusion-weighted MR imaging of the thyroid gland was performed in patients and controls. The apparent diffusion coefficient (ADC) value of the thyroid gland was calculated and correlated with Tc-99m uptake and thyroid function tests of the patients. Results There was a significant difference in the ADC value of the thyroid gland between patients and the control group (P=0.001). The mean ADC value of the thyroid gland in Graves’ disease was 2.03±0.28×10–3 mm2/sec, and in patients with painless thyroiditis 1.46±0.22×10–3 mm2/sec, respectively. There was a significant difference in the ADC values between Graves’ disease and painless thyroiditis (P=0.001). When the ADC value of 1.45×10–3 mm2/sec was used as a threshold value for differentiating Graves’ disease from painless thyroiditis, the best result was obtained with area under the curve of 0.934, accuracy of 83.8%, sensitivity of 95.8%, and specificity of 61.5%. The mean ADC value of the thyroid gland in patients positively correlated with serum TRAb and Tc-99m uptake (r=0.57, P=0.001 and r=0.74, P=0.001, respectively). Conclusions We concluded that ADC values of the thyroid gland can be used to differentiate Graves’ disease from painless thyroiditis in patients with untreated thyrotoxicosis. PMID:29662585

Role of Diffusion-Weighted Magnetic Resonance (MR) Imaging in Differentiation Between Graves' Disease and Painless Thyroiditis.

PubMed

Abdel Razek, Ahmed Abdel Khalek; Abd Allah, Sieza Samir; El-Said, Amr Abd El-Hamid

2017-01-01

To assess the role of diffusion-weighted MR imaging in differentiation between Graves' disease and painless thyroiditis. A prospective study was conducted among 37 consecutive patients with untreated thyrotoxicosis (25 female and 12 male; mean age of 44 years) and 15 ageand sex-matched controls. Diffusion-weighted MR imaging of the thyroid gland was performed in patients and controls. The apparent diffusion coefficient (ADC) value of the thyroid gland was calculated and correlated with Tc-99m uptake and thyroid function tests of the patients. There was a significant difference in the ADC value of the thyroid gland between patients and the control group ( P =0.001). The mean ADC value of the thyroid gland in Graves' disease was 2.03±0.28×10 -3 mm 2 /sec, and in patients with painless thyroiditis 1.46±0.22×10 -3 mm 2 /sec, respectively. There was a significant difference in the ADC values between Graves' disease and painless thyroiditis ( P =0.001). When the ADC value of 1.45×10 -3 mm 2 /sec was used as a threshold value for differentiating Graves' disease from painless thyroiditis, the best result was obtained with area under the curve of 0.934, accuracy of 83.8%, sensitivity of 95.8%, and specificity of 61.5%. The mean ADC value of the thyroid gland in patients positively correlated with serum TRAb and Tc-99m uptake ( r =0.57, P =0.001 and r =0.74, P =0.001, respectively). We concluded that ADC values of the thyroid gland can be used to differentiate Graves' disease from painless thyroiditis in patients with untreated thyrotoxicosis.

Differentiating between Glioblastoma and Primary CNS Lymphoma Using Combined Whole-tumor Histogram Analysis of the Normalized Cerebral Blood Volume and the Apparent Diffusion Coefficient.

PubMed

Bao, Shixing; Watanabe, Yoshiyuki; Takahashi, Hiroto; Tanaka, Hisashi; Arisawa, Atsuko; Matsuo, Chisato; Wu, Rongli; Fujimoto, Yasunori; Tomiyama, Noriyuki

2018-05-31

This study aimed to determine whether whole-tumor histogram analysis of normalized cerebral blood volume (nCBV) and apparent diffusion coefficient (ADC) for contrast-enhancing lesions can be used to differentiate between glioblastoma (GBM) and primary central nervous system lymphoma (PCNSL). From 20 patients, 9 with PCNSL and 11 with GBM without any hemorrhagic lesions, underwent MRI, including diffusion-weighted imaging and dynamic susceptibility contrast perfusion-weighted imaging before surgery. Histogram analysis of nCBV and ADC from whole-tumor voxels in contrast-enhancing lesions was performed. An unpaired t-test was used to compare the mean values for each type of tumor. A multivariate logistic regression model (LRM) was performed to classify GBM and PCNSL using the best parameters of ADC and nCBV. All nCBV histogram parameters of GBMs were larger than those of PCNSLs, but only average nCBV was statistically significant after Bonferroni correction. Meanwhile, ADC histogram parameters were also larger in GBM compared to those in PCNSL, but these differences were not statistically significant. According to receiver operating characteristic curve analysis, the nCBV average and ADC 25th percentile demonstrated the largest area under the curve with values of 0.869 and 0.838, respectively. The LRM combining these two parameters differentiated between GBM and PCNSL with a higher area under the curve value (Logit (P) = -21.12 + 10.00 × ADC 25th percentile (10 -3 mm 2 /s) + 5.420 × nCBV mean, P < 0.001). Our results suggest that whole-tumor histogram analysis of nCBV and ADC combined can be a valuable objective diagnostic method for differentiating between GBM and PCNSL.

[The value of high resolution diffusion weighted imaging in differentiating benign and malignant epithelial tumors of parotid gland].

PubMed

Wen, B H; Cheng, J L; Zhang, H X; Zhang, Z X; Wang, F F; Xue, K K

2018-05-08

Objective: To investigate the diagnostic value of RESOLVE DWI in the evaluation of benign and malignant epithelial tumors of parotid gland. Methods: A total of 106 patients in the First Affiliated Hospital of Zhengzhou University with epithelial tumors of parotid gland confirmed by pathology from July 2015 to October 2017 were retrospectively analyzed. All patients underwent preoperative routine MRI and RESOLVE DWI, the ADC average values were calculated, t test were used to compare the ADC values of benign and malignant epithelial tumors of parotid gland. Diagnostic performance of ADC value was compared using receiver operating characteristic (ROC)curves. Results: All lesions were solitary, including 69 benign epithelial tumors and 37 malignant epithelial tumors. The mean ADC values of pleomorphic adenoma and basal cell adenoma, adenolymphoma and malignant epithelial tumors were (1.47±0.16)×10(-3) mm(2)/s, (0.83±0.19)×10(-3) mm(2)/s and(1.14±0.14)×10(-3) mm(2)/s, the mean ADC value of adenolymphoma lower than the rest of the two groups, there were statistically significant differences among them ( P <0.05). Using 0.94×10(-3) mm(2)/s≤ADC value≤1.28×10(-3)mm(2)/s as the critical value for diagnosing malignant epithelial tumors of parotid gland and comparing with pathological results, the result obtained had a sensitivity of 81.1%, specificity of 88.9%. ADC value had high correlations compared with pathological results, kappa value was 0.600. Conclusion: RESOLVE DWI can be applied in differential diagnosis between benign and malignant epithelial tumors of parotid gland.

Utility of histogram analysis of apparent diffusion coefficient maps obtained using 3.0T MRI for distinguishing uterine carcinosarcoma from endometrial carcinoma.

PubMed

Takahashi, Masahiro; Kozawa, Eito; Tanisaka, Megumi; Hasegawa, Kousei; Yasuda, Masanori; Sakai, Fumikazu

2016-06-01

We explored the role of histogram analysis of apparent diffusion coefficient (ADC) maps for discriminating uterine carcinosarcoma and endometrial carcinoma. We retrospectively evaluated findings in 13 patients with uterine carcinosarcoma and 50 patients with endometrial carcinoma who underwent diffusion-weighted imaging (b = 0, 500, 1000 s/mm(2) ) at 3T with acquisition of corresponding ADC maps. We derived histogram data from regions of interest drawn on all slices of the ADC maps in which tumor was visualized, excluding areas of necrosis and hemorrhage in the tumor. We used the Mann-Whitney test to evaluate the capacity of histogram parameters (mean ADC value, 5th to 95th percentiles, skewness, kurtosis) to discriminate uterine carcinosarcoma and endometrial carcinoma and analyzed the receiver operating characteristic (ROC) curve to determine the optimum threshold value for each parameter and its corresponding sensitivity and specificity. Carcinosarcomas demonstrated significantly higher mean vales of ADC, 95th, 90th, 75th, 50th, 25th percentiles and kurtosis than endometrial carcinomas (P < 0.05). ROC curve analysis of the 75th percentile yielded the best area under the ROC curve (AUC; 0.904), sensitivity of 100%, and specificity of 78.0%, with a cutoff value of 1.034 × 10(-3) mm(2) /s. Histogram analysis of ADC maps might be helpful for discriminating uterine carcinosarcomas and endometrial carcinomas. J. Magn. Reson. Imaging 2016;43:1301-1307. © 2015 Wiley Periodicals, Inc.

Technical Note: A safe, cheap, and easy-to-use isotropic diffusion MRI phantom for clinical and multicenter studies.

PubMed

Pullens, Pim; Bladt, Piet; Sijbers, Jan; Maas, Andrew I R; Parizel, Paul M

2017-03-01

Since Diffusion Weighted Imaging (DWI) data acquisition and processing are not standardized, substantial differences in DWI derived measures such as Apparent Diffusion Coefficient (ADC) may arise which are related to the acquisition or MRI processing method, but not to the sample under study. Quality assurance using a standardized test object, or phantom, is a key factor in standardizing DWI across scanners. Current diffusion phantoms are either complex to use, not available in larger quantities, contain substances unwanted in a clinical environment, or are expensive. A diffusion phantom based on a polyvinylpyrrolidone (PVP) solution, together with a phantom holder, is presented and compared to existing diffusion phantoms for use in clinical DWI scans. An ADC vs. temperature calibration curve was obtained. ADC of the phantom (808 to 857 ± 0.2 mm 2 /s) is in the same range as ADC values found in brain tissue. ADC measurements are highly reproducible across time with an intra-class correlation coefficient of > 0.8. ADC as function of temperature (in Kelvin) can be estimated as ADCm(T)=[exp(-7.09)·exp-2903.81T-1293.55] with a total uncertainty (95% confidence limit) of ± 1.7%. We present an isotropic diffusion MRI phantom, together with its temperature calibration curve, that is easy-to-use in a clinical environment, cost-effective, reproducible to produce, and that contains no harmful substances. © 2017 American Association of Physicists in Medicine.

A mixed signal ECG processing platform with an adaptive sampling ADC for portable monitoring applications.

PubMed

Kim, Hyejung; Van Hoof, Chris; Yazicioglu, Refet Firat

2011-01-01

This paper describes a mixed-signal ECG processing platform with an 12-bit ADC architecture that can adapt its sampling rate according to the input signals rate of change. This enables the sampling of ECG signals with significantly reduced data rate without loss of information. The presented adaptive sampling scheme reduces the ADC power consumption, enables the processing of ECG signals with lower power consumption, and reduces the power consumption of the radio while streaming the ECG signals. The test results show that running a CWT-based R peak detection algorithm using the adaptively sampled ECG signals consumes only 45.6 μW and it leads to 36% less overall system power consumption.

Differentiation of orbital lymphoma and idiopathic orbital inflammatory pseudotumor: combined diagnostic value of conventional MRI and histogram analysis of ADC maps.

PubMed

Ren, Jiliang; Yuan, Ying; Wu, Yingwei; Tao, Xiaofeng

2018-05-02

The overlap of morphological feature and mean ADC value restricted clinical application of MRI in the differential diagnosis of orbital lymphoma and idiopathic orbital inflammatory pseudotumor (IOIP). In this paper, we aimed to retrospectively evaluate the combined diagnostic value of conventional magnetic resonance imaging (MRI) and whole-tumor histogram analysis of apparent diffusion coefficient (ADC) maps in the differentiation of the two lesions. In total, 18 patients with orbital lymphoma and 22 patients with IOIP were included, who underwent both conventional MRI and diffusion weighted imaging before treatment. Conventional MRI features and histogram parameters derived from ADC maps, including mean ADC (ADC mean ), median ADC (ADC median ), skewness, kurtosis, 10th, 25th, 75th and 90th percentiles of ADC (ADC 10 , ADC 25 , ADC 75 , ADC 90 ) were evaluated and compared between orbital lymphoma and IOIP. Multivariate logistic regression analysis was used to identify the most valuable variables for discriminating. Differential model was built upon the selected variables and receiver operating characteristic (ROC) analysis was also performed to determine the differential ability of the model. Multivariate logistic regression showed ADC 10 (P = 0.023) and involvement of orbit preseptal space (P = 0.029) were the most promising indexes in the discrimination of orbital lymphoma and IOIP. The logistic model defined by ADC 10 and involvement of orbit preseptal space was built, which achieved an AUC of 0.939, with sensitivity of 77.30% and specificity of 94.40%. Conventional MRI feature of involvement of orbit preseptal space and ADC histogram parameter of ADC 10 are valuable in differential diagnosis of orbital lymphoma and IOIP.

Correlation between apparent diffusion coefficient value on diffusion-weighted MR imaging and Gleason score in prostate cancer.

PubMed

Wu, X; Reinikainen, P; Vanhanen, A; Kapanen, M; Vierikko, T; Ryymin, P; Hyödynmaa, S; Kellokumpu-Lehtinen, P-L

2017-01-01

To investigate whether diffusion-weighted imaging (DWI) apparent diffusion coefficient (ADC) correlates with prostate cancer aggressiveness and further to compare the diagnostic performance of ADC and normalized ADC (nADC: normalized to non-tumor tissue). Thirty pre-treatment patients (mean age, 69years; range: 59-78years) with prostate cancer underwent magnetic resonance imaging (MRI) examination, including DWI with three b values: 50, 400, and 800s/mm 2 . Both ADC and nADC were correlated with the Gleason score obtained through transrectal ultrasound-guided biopsy. The tumor minimum ADC (ADC min : the lowest ADC value within tumor) had an inverse correlation with the Gleason score (r=-0.43, P<0.05), and it was lower in patients with Gleason score 3+4 than in those with Gleason score 3+3 (0.54±0.11×10 3 mm 2 /s vs. 0.64±0.12×10 -3 mm 2 /s, P<0.05). Both the nADC min and nADC mean correlated with the Gleason score (r=-0.52 and r=-0.55, P<0.01; respectively), and they were lower in patients with Gleason score 3+4 than those with Gleason score 3+3 (P<0.01; respectively). Receiver operating characteristic (ROC) analysis showed that the area under the ROC curve was 0.765, 0.818, or 0.833 for the ADC min , nADC min , or nADC mean ; respectively, in differentiating between Gleason score 3+4 and 3+3 tumors. Tumor ADC min , nADC min , and nADC mean are useful markers to predict the aggressiveness of prostate cancer. Copyright © 2016 Éditions françaises de radiologie. Published by Elsevier Masson SAS. All rights reserved.

High fidelity, radiation tolerant analog-to-digital converters

NASA Technical Reports Server (NTRS)

Wang, Charles Chang-I (Inventor); Linscott, Ivan Richard (Inventor); Inan, Umran S. (Inventor)

2012-01-01

Techniques for an analog-to-digital converter (ADC) using pipeline architecture includes a linearization technique for a spurious-free dynamic range (SFDR) over 80 deciBels. In some embodiments, sampling rates exceed a megahertz. According to a second approach, a switched-capacitor circuit is configured for correct operation in a high radiation environment. In one embodiment, the combination yields high fidelity ADC (>88 deciBel SFDR) while sampling at 5 megahertz sampling rates and consuming <60 milliWatts. Furthermore, even though it is manufactured in a commercial 0.25-.mu.m CMOS technology (1 .mu.m=12.sup.-6 meters), it maintains this performance in harsh radiation environments. Specifically, the stated performance is sustained through a highest tested 2 megarad(Si) total dose, and the ADC displays no latchup up to a highest tested linear energy transfer of 63 million electron Volts square centimeters per milligram at elevated temperature (131 degrees C.) and supply (2.7 Volts, versus 2.5 Volts nominal).

Ultra-high field diffusion tensor imaging of articular cartilage correlated with histology and scanning electron microscopy.

PubMed

Raya, José G; Arnoldi, Andreas P; Weber, Daniel L; Filidoro, Lucianna; Dietrich, Olaf; Adam-Neumair, Silvia; Mützel, Elisabeth; Melkus, Gerd; Putz, Reinhard; Reiser, Maximilian F; Jakob, Peter M; Glaser, Christian

2011-08-01

To investigate the relationship of the different diffusion tensor imaging (DTI) parameters (ADC, FA, and first eigenvector (EV)) to the constituents (proteoglycans and collagen), the zonal arrangement of the collagen network, and mechanical loading of articular cartilage. DTI of eight cartilage-on-bone samples of healthy human patellar cartilage was performed at 17.6 T. Three samples were additionally imaged under indentation loading. After DTI, samples underwent biomechanical testing, safranin-O staining for semiquantitative proteoglycan estimation, and scanning electron microscopy (SEM) for depicting collagen architecture. From the articular surface to the bone-cartilage interface, ADC continuously decreased and FA increased. Cartilage zonal heights calculated from EVs strongly correlated with SEM-derived zonal heights (P < 0.01, r (2)=0.87). Compression reduced ADC in the superficial 30% of cartilage and increased FA in the superficial 5% of cartilage. Reorientation of the EVs indicative of collagen fiber reorientation under the indenter was observed. No significant correlation was found between ADC, FA, and compressive stiffness. Correlating ADC and FA with proteoglycan and collagen content suggests that diffusion is dominated by different depth-dependent mechanisms within cartilage. Knowledge of the spatial distribution of the DTI parameters and their variation contributes to form a database for future analysis of defective cartilage.

Controlled Substance Reconciliation Accuracy Improvement Using Near Real-Time Drug Transaction Capture from Automated Dispensing Cabinets.

PubMed

Epstein, Richard H; Dexter, Franklin; Gratch, David M; Perino, Michael; Magrann, Jerry

2016-06-01

Accurate accounting of controlled drug transactions by inpatient hospital pharmacies is a requirement in the United States under the Controlled Substances Act. At many hospitals, manual distribution of controlled substances from pharmacies is being replaced by automated dispensing cabinets (ADCs) at the point of care. Despite the promise of improved accountability, a high prevalence (15%) of controlled substance discrepancies between ADC records and anesthesia information management systems (AIMS) has been published, with a similar incidence (15.8%; 95% confidence interval [CI], 15.3% to 16.2%) noted at our institution. Most reconciliation errors are clerical. In this study, we describe a method to capture drug transactions in near real-time from our ADCs, compare them with documentation in our AIMS, and evaluate subsequent improvement in reconciliation accuracy. ADC-controlled substance transactions are transmitted to a hospital interface server, parsed, reformatted, and sent to a software script written in Perl. The script extracts the data and writes them to a SQL Server database. Concurrently, controlled drug totals for each patient having care are documented in the AIMS and compared with the balance of the ADC transactions (i.e., vending, transferring, wasting, and returning drug). Every minute, a reconciliation report is available to anesthesia providers over the hospital Intranet from AIMS workstations. The report lists all patients, the current provider, the balance of ADC transactions, the totals from the AIMS, the difference, and whether the case is still ongoing or had concluded. Accuracy and latency of the ADC transaction capture process were assessed via simulation and by comparison with pharmacy database records, maintained by the vendor on a central server located remotely from the hospital network. For assessment of reconciliation accuracy over time, data were collected from our AIMS from January 2012 to June 2013 (Baseline), July 2013 to April 2014 (Next Day Reports), and May 2014 to September 2015 (Near Real-Time Reports) and reconciled against pharmacy records from the central pharmacy database maintained by the vendor. Control chart (batch means) methods were used between successive epochs to determine if improvement had taken place. During simulation, 100% of 10,000 messages, transmitted at a rate of 1295 per minute, were accurately captured and inserted into the database. Latency (transmission time to local database insertion time) was 46.3 ± 0.44 milliseconds (SEM). During acceptance testing, only 1 of 1384 transactions analyzed had a difference between the near real-time process and what was in the central database; this was for a "John Doe" patient whose name had been changed subsequent to data capture. Once a transaction was entered at the ADC workstation, 84.9% (n = 18 bins; 95% CI, 78.4% to 91.3%) of these transactions were available in the database on the AIMS server within 2 minutes. Within 5 minutes, 98.2% (n = 18 bins; 95% CI, 97.2% to 99.3%) were available. Among 145,642 transactions present in the central pharmacy database, only 24 were missing from the local database table (mean = 0.018%; 95% CI, 0.002% to 0.034%). Implementation of near real-time reporting improved the controlled substance reconciliation error rate compared to the previous Next Day Reports epoch, from 8.8% to 5.2% (difference = -3.6%; 95% CI, -4.3% to -2.8%; P < 10). Errors were distributed among staff, with 50% of discrepancies accounted for by 12.4% of providers and 80% accounted for by 28.5% of providers executing transactions during the Near Real-Time Reports epoch. The near real-time system for the capture of transactional data flowing over the hospital network was highly accurate, reliable, and exhibited acceptable latency. This methodology can be used to implement similar data capture for transactions from their drug ADCs. Reconciliation accuracy improved significantly as a result of implementation. Our approach may be of particular utility at facilities with limited pharmacy resources to audit anesthesia records for controlled substance administration and reconcile them against dispensing records.

High-speed, multi-channel detector readout electronics for fast radiation detectors

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

Hennig, Wolfgang

2012-06-22

In this project, we are developing a high speed digital spectrometer that a) captures detector waveforms at rates up to 500 MSPS b) has upgraded event data acquisition with additional data buffers for zero dead time operation c) moves energy calculations to the FPGA to increase spectrometer throughput in fast scintillator applications d) uses a streamlined architecture and high speed data interface for even faster readout to the host PC These features are in addition to the standard functions in our existing spectrometers such as digitization, programmable trigger and energy filters, pileup inspection, data acquisition with energy and time stamps,more » MCA histograms, and run statistics. In Phase I, we upgraded one of our existing spectrometer designs to demonstrate the key principle of fast waveform capture using a 500 MSPS, 12 bit ADC and a Xilinx Virtex-4 FPGA. This upgraded spectrometer, named P500, performed well in initial tests of energy resolution, pulse shape analysis, and timing measurements, thus achieving item (a) above. In Phase II, we are revising the P500 to build a commercial prototype with the improvements listed in items (b)-(d). As described in the previous report, two devices were built to pursue this goal, named the Pixie-500 and the Pixie-500 Express. The Pixie-500 has only minor improvements from the Phase I prototype and is intended as an early commercial product (its production and part of its development were funded outside the SBIR). It also allows testing of the ADC performance in real applications.The Pixie-500 Express (or Pixie-500e) includes all of the improvements (b)-(d). At the end of Phase II of the project, we have tested and debugged the hardware, firmware and software of the Pixie-500 Express prototype boards delivered 12/3/2010. This proved substantially more complex than anticipated. At the time of writing, all hardware bugs have been fixed, the PCI Express interface is working, the SDRAM has been successfully tested and the SHARC DSP has been booted with preliminary code. All new ICs and circuitry on the prototype are working properly, however some of the planned firmware and software functions have not yet been completely implemented and debugged. Overall, due to the unanticipated complexity of the PCI Express interface, some aspects of the project could not be completed with the time and funds available in Phase II. These aspects will be completed in self-funded Phase III.« less

Diagnostic Accuracy of Centrally Restricted Diffusion in the Differentiation of Treatment-Related Necrosis from Tumor Recurrence in High-Grade Gliomas.

PubMed

Zakhari, N; Taccone, M S; Torres, C; Chakraborty, S; Sinclair, J; Woulfe, J; Jansen, G H; Nguyen, T B

2018-02-01

Centrally restricted diffusion has been demonstrated in recurrent high-grade gliomas treated with bevacizumab. Our purpose was to assess the accuracy of centrally restricted diffusion in the diagnosis of radiation necrosis in high-grade gliomas not treated with bevacizumab. In this prospective study, we enrolled patients with high-grade gliomas who developed a new ring-enhancing necrotic lesion and who underwent re-resection. The presence of a centrally restricted diffusion within the ring-enhancing lesion was assessed visually on diffusion trace images and by ADC measurements on 3T preoperative diffusion tensor examination. The percentage of tumor recurrence and radiation necrosis in each surgical specimen was defined histopathologically. The association between centrally restricted diffusion and radiation necrosis was assessed using the Fisher exact test. Differences in ADC and the ADC ratio between the groups were assessed via the Mann-Whitney U test, and receiver operating characteristic curve analysis was performed. Seventeen patients had re-resected ring-enhancing lesions: 8 cases of radiation necrosis and 9 cases of tumor recurrence. There was significant association between centrally restricted diffusion by visual assessment and radiation necrosis ( P = .015) with a sensitivity of 75% and a specificity of 88.9%, a positive predictive value 85.7%, and a negative predictive value of 80% for the diagnosis of radiation necrosis. There was a statistically significant difference in the ADC and ADC ratio between radiation necrosis and tumor recurrence ( P = .027). The presence of centrally restricted diffusion in a new ring-enhancing lesion might indicate radiation necrosis rather than tumor recurrence in high-grade gliomas previously treated with standard chemoradiation without bevacizumab. © 2018 by American Journal of Neuroradiology.

How to create a very-low cost, very-low-power, credit-card-sized and real-time ready datalogger

NASA Astrophysics Data System (ADS)

Bès de Berc, Maxime; Grunberg, Marc; Engels, Fabien

2014-05-01

In some cases a field instrumentalist could have to add some extra sensors in a remote station. Additional ADCs (Analogic Digital Converters) are not always implemented on commercial dataloggers, or may already be used. Adding more ADCs often implies an expensive development, or buy a new datalogger. We present here a very simple way to deploy an embedded ARM computer, use its features and embedded ADCs to create datas in a seismological standard format and integrating it within the real-time data stream from the station. In the past few years, because of the market growth of telephony and mobile applications, the ARM processor from ARM Ltd has become very common and available at a reasonable price. This processor has the particularity to be an excellent compromise between its frequency and its power consumption. That's why most of smartphones and tablets feature nowadays that kind of processor. It is also available on the market as Soc (System on Chip) or complete embedded computer. The most known is probably the Raspberry Pi, but many ohers exist like the BeagleBone or BeagleBoard. This kind of computer can be bought between 35€ for Raspberry Pi and several hundred Euro for more industrial products. Each model often embed some ADCs on its chip or some special buses, allowing additional ADCs to be easily used. Our experiment has been made on a BeagleBone platform, available at 78€. We chose it because its a more mature product than Raspberry Pi, it has all connectors and options needed: seven ADCs, an USB port for local backup, an Ethernet port for real-time streams, and some useful things like GPIO and I2C buses. Our goal was to plug temperature and humidity sensors on the ADCs, read datas, record them in mini-SEED format (Standard for the Exchange of the Earthquake Data), and transmit those datas to a central server as a secondary source for a remote station, by using Seedlink, which is a standard for seismology. Seedlink is a real-time data acquisition protocol and a client-server software that implements this protocol. We first discuss on how install a linux Os, and a Seedlink server on this platform. We then explain how we developed a very simple plugin for the Seedlink server, for reading, preparing, sending and recording datas in mini-Seed format, and how we implemented it in the whole data stream. We later evaluate the quality of this low-cost datalogger, with methods we normally use with our commercial seismological dataloggers. We finally talk about how deploy several platform with the same disk image as quickly as possible.

Histogram analysis of apparent diffusion coefficient at 3.0 T in urinary bladder lesions: correlation with pathologic findings.

PubMed

Suo, Shi-Teng; Chen, Xiao-Xi; Fan, Yu; Wu, Lian-Ming; Yao, Qiu-Ying; Cao, Meng-Qiu; Liu, Qiang; Xu, Jian-Rong

2014-08-01

To investigate the potential value of histogram analysis of apparent diffusion coefficient (ADC) obtained at standard (700 s/mm(2)) and high (1500 s/mm(2)) b values on a 3.0-T scanner in the differentiation of bladder cancer from benign lesions and in assessing bladder tumors of different pathologic T stages and to evaluate the diagnostic performance of ADC-based histogram parameters. In all, 52 patients with bladder lesions, including benign lesions (n = 7) and malignant tumors (n = 45; T1 stage or less, 23; T2 stage, 7; T3 stage, 8; and T4 stage, 7), were retrospectively evaluated. Magnetic resonance examination at 3.0 T and diffusion-weighted imaging were performed. ADC maps were obtained at two b values (b = 700 and 1500 s/mm(2); ie, ADC-700 and ADC-1500). Parameters of histogram analysis included mean, kurtosis, skewness, and entropy. The correlations between these parameters and pathologic results were revealed. Receiver operating characteristic (ROC) curves were generated to determine the diagnostic value of histogram parameters. Significant differences were found in mean ADC-700, mean ADC-1500, skewness ADC-1500, and kurtosis ADC-1500 between bladder cancer and benign lesions (P = .002-.032). There were also significant differences in mean ADC-700, mean ADC-1500, and kurtosis ADC-1500 among bladder tumors of different pathologic T stages (P = .000-.046). No significant differences were observed in other parameters. Mean ADC-1500 and kurtosis ADC-1500 were significantly correlated with T stage, respectively (ρ = -0.614, P < .001; ρ = 0.374, P = .011). ROC analysis showed that the combination of mean ADC-1500 and kurtosis ADC-1500 has the maximal area under the ROC curve (AUC, 0.894; P < .001) in the differentiation of benign lesions and malignant tumors, with a sensitivity of 77.78% and specificity of 100%. AUCs for differentiating low- and high-stage tumors were 0.840 for mean ADC-1500 (P < .001) and 0.696 for kurtosis ADC-1500 (P = .015). Histogram analysis of ADC-1500 at 3.0 T can be useful in evaluation of bladder lesions. A combination of mean ADC-1500 and kurtosis ADC-1500 may be more beneficial in the differentiation of benign and malignant lesions. Mean ADC-1500 was the most promising parameter for differentiating low- from high-stage bladder cancer. Copyright © 2014 AUR. Published by Elsevier Inc. All rights reserved.

Locally advanced rectal cancer: post-chemoradiotherapy ADC histogram analysis for predicting a complete response.

PubMed

Cho, Seung Hyun; Kim, Gab Chul; Jang, Yun-Jin; Ryeom, Hunkyu; Kim, Hye Jung; Shin, Kyung-Min; Park, Jun Seok; Choi, Gyu-Seog; Kim, See Hyung

2015-09-01

The value of diffusion-weighted imaging (DWI) for reliable differentiation between pathologic complete response (pCR) and residual tumor is still unclear. Recently, a few studies reported that histogram analysis can be helpful to monitor the therapeutic response in various cancer research. To investigate whether post-chemoradiotherapy (CRT) apparent diffusion coefficient (ADC) histogram analysis can be helpful to predict a pCR in locally advanced rectal cancer (LARC). Fifty patients who underwent preoperative CRT followed by surgery were enrolled in this retrospective study, non-pCR (n = 41) and pCR (n = 9), respectively. ADC histogram analysis encompassing the whole tumor was performed on two post-CRT ADC600 and ADC1000 (b factors 0, 600 vs. 0, 1000 s/mm(2)) maps. Mean, minimum, maximum, SD, mode, 10th, 25th, 50th, 75th, 90th percentile ADCs, skewness, and kurtosis were derived. Diagnostic performance for predicting pCR was evaluated and compared. On both maps, 10th and 25th ADCs showed better diagnostic performance than that using mean ADC. Tenth percentile ADCs revealed the best diagnostic performance on both ADC600 (AZ 0.841, sensitivity 100%, specificity 70.7%) and ADC1000 (AZ 0.821, sensitivity 77.8%, specificity 87.8%) maps. In comparison between 10th percentile and mean ADC, the specificity was significantly improved on both ADC600 (70.7% vs. 53.7%; P = 0.031) and ADC1000 (87.8% vs. 73.2%; P = 0.039) maps. Post-CRT ADC histogram analysis is helpful for predicting pCR in LARC, especially, in improving the specificity, compared with mean ADC. © The Foundation Acta Radiologica 2014.

A simple and versatile phase detector for heterodyne interferometers

NASA Astrophysics Data System (ADS)

Mlynek, A.; Faugel, H.; Eixenberger, H.; Pautasso, G.; Sellmair, G.

2017-02-01

The measurement of the relative phase of two sinusoidal electrical signals is a frequently encountered task in heterodyne interferometry, but also occurs in many other applications. Especially in interferometry, multi-radian detectors are often required, which track the temporal evolution of the phase difference and are able to register phase changes that exceed 2π. While a large variety of solutions to this problem is already known, we present an alternative approach, which pre-processes the signals with simple analog circuitry and digitizes two resulting voltages with an analog-to-digital converter (ADC), whose sampling frequency can be far below the frequency of the sinusoidal signals. Phase reconstruction is finally carried out by software. The main advantage of this approach is its simplicity, using only few low-cost hardware components and a standard 2-channel ADC with low performance requirements. We present an application on the two-color interferometer of the ASDEX Upgrade tokamak, where the relative phase of 40 MHz sinusoids is measured.

Radio Astronomy Software Defined Receiver Project

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

Vacaliuc, Bogdan; Leech, Marcus; Oxley, Paul

The paper describes a Radio Astronomy Software Defined Receiver (RASDR) that is currently under development. RASDR is targeted for use by amateurs and small institutions where cost is a primary consideration. The receiver will operate from HF thru 2.8 GHz. Front-end components such as preamps, block down-converters and pre-select bandpass filters are outside the scope of this development and will be provided by the user. The receiver includes RF amplifiers and attenuators, synthesized LOs, quadrature down converters, dual 8 bit ADCs and a Signal Processor that provides firmware processing of the digital bit stream. RASDR will interface to a usermore » s PC via a USB or higher speed Ethernet LAN connection. The PC will run software that provides processing of the bit stream, a graphical user interface, as well as data analysis and storage. Software should support MAC OS, Windows and Linux platforms and will focus on such radio astronomy applications as total power measurements, pulsar detection, and spectral line studies.« less

Whole-tumor apparent diffusion coefficient (ADC) histogram analysis to differentiate benign peripheral neurogenic tumors from soft tissue sarcomas.

PubMed

Nakajo, Masanori; Fukukura, Yoshihiko; Hakamada, Hiroto; Yoneyama, Tomohide; Kamimura, Kiyohisa; Nagano, Satoshi; Nakajo, Masayuki; Yoshiura, Takashi

2018-02-22

Apparent diffusion coefficient (ADC) histogram analyses have been used to differentiate tumor grades and predict therapeutic responses in various anatomic sites with moderate success. To determine the ability of diffusion-weighted imaging (DWI) with a whole-tumor ADC histogram analysis to differentiate benign peripheral neurogenic tumors (BPNTs) from soft tissue sarcomas (STSs). Retrospective study, single institution. In all, 25 BPNTs and 31 STSs. Two-b value DWI (b-values = 0, 1000s/mm 2 ) was at 3.0T. The histogram parameters of whole-tumor for ADC were calculated by two radiologists and compared between BPNTs and STSs. Nonparametric tests were performed for comparisons between BPNTs and STSs. P < 0.05 was considered statistically significant. The ability of each parameter to differentiate STSs from BPNTs was evaluated using area under the curve (AUC) values derived from a receiver operating characteristic curve analysis. The mean ADC and all percentile parameters were significantly lower in STSs than in BPNTs (P < 0.001-0.009), with AUCs of 0.703-0.773. However, the coefficient of variation (P = 0.020 and AUC = 0.682) and skewness (P = 0.012 and AUC = 0.697) were significantly higher in STSs than in BPNTs. Kurtosis (P = 0.295) and entropy (P = 0.604) did not differ significantly between BPNTs and STSs. Whole-tumor ADC histogram parameters except kurtosis and entropy differed significantly between BPNTs and STSs. 3 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018. © 2018 International Society for Magnetic Resonance in Medicine.

Apparent diffusion coefficient value of diffusion-weighted imaging for differential diagnosis of ductal carcinoma in situ and infiltrating ductal carcinoma.

PubMed

Ding, Jian-Rong; Wang, Dong-Nv; Pan, Jing-Li

2016-01-01

The present meta-analysis investigated the clinical value of apparent diffusion coefficient (ADC) values in diffusion-weighted imaging (DWI) for differential diagnosis of ductal carcinoma in situ (DCIS) and infiltrating ductal carcinoma (IDC). Electronic databases searches were employed to identify relevant scientific literature, and the search results were screened to selected high-quality studies for this meta-analysis. Methodological quality of the enrolled studies was evaluated by quality evaluation of diagnostic accuracy studies (QUADAS). Summary odds ratios (ORs) and its corresponding 95% confidence interval (95% CI) were calculated for DCIS versus IDC category of ADC value using Z test. Our meta-analysis contained a combined total of 1,097 subjects (928 patients with IDC and 169 patients with DCIS) from 9 relevant high-quality cohort studies. Pooled ORs demonstrated that ADC value in IDC patients was significantly lower than DCIS patients. Subgroup analysis stratified by ethnicity indicated a higher ADC value in DCIS patients compared to IDC, in Asian population, but not in Caucasians. Magnetic resonance imaging (MRI) machine type-stratified analysis revealed that the ADC value of DWI obtained from both non- General Electric Company (GE) 1.5T and GE 1.5T machines were highly reliable in the differential diagnosis of DCIS and IDC. Our meta-analysis provides evidence that ADC values in DWI accurately conveys the differences in tumor architecture between IDC and DCIS, which has high clinical value in differentiatal diagnosis of IDC and DCIS. This may lead to improved BC prediction and treatment.

Diffusion-weighted imaging in the evaluation of odontogenic cysts and tumours.

PubMed

Srinivasan, K; Seith Bhalla, A; Sharma, R; Kumar, A; Roychoudhury, A; Bhutia, O

2012-10-01

The differentiation between keratocystic odontogenic tumour (KCOT) and other cystic/predominantly cystic odontogenic tumours is difficult on conventional CT and MR sequences as there is overlap in the imaging characteristics of these lesions. The purpose of this study was to evaluate the role of diffusion-weighted imaging (DWI) and to assess the performance of apparent diffusion coefficients (ADCs) in the differential diagnosis of odontogenic cysts and tumours. 20 patients with odontogenic cysts and tumours of the maxillomandibular region were examined with DWI. Diffusion-weighted images were obtained with a single-shot echoplanar technique with b-values of 0, 500 and 1000 s mm(-2). An ADC map was obtained at each slice position. The cystic areas of ameloblastoma (n=10) showed free diffusion with a mean ADC value of 2.192±0.33×10(-3) mm(2) s(-1), whereas the solid areas showed restricted diffusion with a mean ADC value of 1.041±0.41×10(-3) mm(2) s(-1). KCOT (n=5) showed restricted diffusion with a mean ADC value of 1.019±0.07×10(-3) mm(2) s(-1). There was a significant difference between the ADC values of KCOT and cystic ameloblastoma (p<0.01, Mann-Whitney U-test). The cut-off with which KCOT and predominantly cystic ameloblastomas were optimally differentiated was 2.013×10(-3) mm(2) s(-1), which yielded 100% sensitivity and 100% specificity. DWI can be used to differentiate KCOT from cystic (or predominantly cystic) odontogenic tumours.

The Flash ADC system and PMT waveform reconstruction for the Daya Bay experiment

NASA Astrophysics Data System (ADS)

Huang, Yongbo; Chang, Jinfan; Cheng, Yaping; Chen, Zhang; Hu, Jun; Ji, Xiaolu; Li, Fei; Li, Jin; Li, Qiuju; Qian, Xin; Jetter, Soeren; Wang, Wei; Wang, Zheng; Xu, Yu; Yu, Zeyuan

2018-07-01

To better understand the energy response of the Antineutrino Detector (AD), the Daya Bay Reactor Neutrino Experiment installed a full Flash ADC readout system on one AD that allowed for simultaneous data taking with the current readout system. This paper presents the design, data acquisition, and simulation of the Flash ADC system, and focuses on the PMT waveform reconstruction algorithms. For liquid scintillator calorimetry, the most critical requirement to waveform reconstruction is linearity. Several common reconstruction methods were tested but the linearity performance was not satisfactory. A new method based on the deconvolution technique was developed with 1% residual non-linearity, which fulfills the requirement. The performance was validated with both data and Monte Carlo (MC) simulations, and 1% consistency between them has been achieved.

A multiple-drawer medication layout problem in automated dispensing cabinets.

PubMed

Pazour, Jennifer A; Meller, Russell D

2012-12-01

In this paper we investigate the problem of locating medications in automated dispensing cabinets (ADCs) to minimize human selection errors. We formulate the multiple-drawer medication layout problem and show that the problem can be formulated as a quadratic assignment problem. As a way to evaluate various medication layouts, we develop a similarity rating for medication pairs. To solve industry-sized problem instances, we develop a heuristic approach. We use hospital ADC transaction data to conduct a computational experiment to test the performance of our developed heuristics, to demonstrate how our approach can aid in ADC design trade-offs, and to illustrate the potential improvements that can be made when applying an analytical process to the multiple-drawer medication layout problem. Finally, we present conclusions and future research directions.

Brain-water diffusion coefficients reflect the severity of inherited prion disease

PubMed Central

Hyare, H.; Wroe, S.; Siddique, D.; Webb, T.; Fox, N. C.; Stevens, J.; Collinge, J.; Yousry, T.; Thornton, J. S.

2010-01-01

Objective: Inherited prion diseases are progressive neurodegenerative conditions, characterized by cerebral spongiosis, gliosis, and neuronal loss, caused by mutations within the prion protein (PRNP) gene. We wished to assess the potential of diffusion-weighted MRI as a biomarker of disease severity in inherited prion diseases. Methods: Twenty-five subjects (mean age 45.2 years) with a known PRNP mutation including 19 symptomatic patients, 6 gene-positive asymptomatic subjects, and 7 controls (mean age 54.1 years) underwent conventional and diffusion-weighted MRI. An index of normalized brain volume (NBV) and region of interest (ROI) mean apparent diffusion coefficient (ADC) for the head of caudate, putamen, and pulvinar nuclei were recorded. ADC histograms were computed for whole brain (WB) and gray matter (GM) tissue fractions. Clinical assessment utilized standardized clinical scores. Mann-Whitney U test and regression analyses were performed. Results: Symptomatic patients exhibited an increased WB mean ADC (p = 0.006) and GM mean ADC (p = 0.024) compared to controls. Decreased NBV and increased mean ADC measures significantly correlated with clinical measures of disease severity. Using a stepwise multivariate regression procedure, GM mean ADC was an independent predictor of Clinician's Dementia Rating score (p = 0.001), Barthel Index of activities of daily living (p = 0.001), and Rankin disability score (p = 0.019). Conclusions: Brain volume loss in inherited prion diseases is accompanied by increased cerebral apparent diffusion coefficient (ADC), correlating with increased disease severity. The association between gray matter ADC and clinical neurologic status suggests this measure may prove a useful biomarker of disease activity in inherited prion diseases. GLOSSARY ADAS-Cog = Alzheimer's Disease Assessment Scale–Cognitive subscale; ADC = apparent diffusion coefficient; ADL = Barthel Activities of Daily Living scale; BET = brain extraction tool; BPRS = Brief Psychiatric Rating Scale; BSE = bovine spongiform encephalopathy; CDR = Clinician's Dementia Rating Scale; CGIS = Clinician's Global Impression of Disease; CI = confidence interval; DWI = diffusion-weighted imaging; FLAIR = fluid-attenuated inversion recovery; FOV = field of view; GM = gray matter; LC = left head of caudate; LP = left putamen; LPu = left pulvinar; MMSE = Mini-Mental State Examination; NBV = normalized brain volume; PH = peak height; PL = peak location; RC = right head of caudate; RP = right putamen; RPu = right pulvinar; ROI = region of interest; sCJD = sporadic Creutzfeldt-Jakob disease; TE = echo time; TI = inversion time; TR = repetition time; vCJD = variant Creutzfeldt-Jakob disease; WB = whole brain; WM = white matter. PMID:20177119

Differentiation between malignant and benign thyroid nodules and stratification of papillary thyroid cancer with aggressive histological features: Whole-lesion diffusion-weighted imaging histogram analysis.

PubMed

Hao, Yonghong; Pan, Chu; Chen, WeiWei; Li, Tao; Zhu, WenZhen; Qi, JianPin

2016-12-01

To explore the usefulness of whole-lesion histogram analysis of apparent diffusion coefficient (ADC) derived from reduced field-of-view (r-FOV) diffusion-weighted imaging (DWI) in differentiating malignant and benign thyroid nodules and stratifying papillary thyroid cancer (PTC) with aggressive histological features. This Institutional Review Board-approved, retrospective study included 93 patients with 101 pathologically proven thyroid nodules. All patients underwent preoperative r-FOV DWI at 3T. The whole-lesion ADC assessments were performed for each patient. Histogram-derived ADC parameters between different subgroups (pathologic type, extrathyroidal extension, lymph node metastasis) were compared. Receiver operating characteristic curve analysis was used to determine optimal histogram parameters in differentiating benign and malignant nodules and predicting aggressiveness of PTC. Mean ADC, median ADC, 5 th percentile ADC, 25 th percentile ADC, 75 th percentile ADC, 95 th percentile ADC (all P < 0.001), and kurtosis (P = 0.001) were significantly lower in malignant thyroid nodules, and mean ADC achieved the highest AUC (0.919) with a cutoff value of 1842.78 × 10 -6 mm 2 /s in differentiating malignant and benign nodules. Compared to the PTCs without extrathyroidal extension, PTCs with extrathyroidal extension showed significantly lower median ADC, 5 th percentile ADC, and 25 th percentile ADC. The 5 th percentile ADC achieved the highest AUC (0.757) with cutoff value of 911.5 × 10 -6 mm 2 /s for differentiating between PTCs with and without extrathyroidal extension. Whole-lesion ADC histogram analysis might help to differentiate malignant nodules from benign ones and show the PTCs with extrathyroidal extension. J. Magn. Reson. Imaging 2016;44:1546-1555. © 2016 International Society for Magnetic Resonance in Medicine.

Performance evaluation of the analogue front-end and ADC prototypes for the Gotthard-II development

NASA Astrophysics Data System (ADS)

Zhang, J.; Andrä, M.; Barten, R.; Bergamaschi, A.; Brückner, M.; Dinapoli, R.; Fröjdh, E.; Greiffenberg, D.; Lopez-Cuenca, C.; Mezza, D.; Mozzanica, A.; Ramilli, M.; Redford, S.; Ruat, M.; Ruder, C.; Schmitt, B.; Shi, X.; Thattil, D.; Tinti, G.; Turcato, M.; Vetter, S.

2017-12-01

Gotthard-II is a silicon microstrip detector developed for the European X-ray Free-Electron Laser (XFEL.EU). Its potential scientific applications include X-ray absorption/emission spectroscopy, hard X-ray high resolution single-shot spectrometry (HiREX), energy dispersive experiments at 4.5 MHz frame rate, beam diagnostics, as well as veto signal generation for pixel detectors. Gotthard-II uses a silicon microstrip sensor with a pitch of 50 μm or 25 μm and with 1280 or 2560 channels wire-bonded to readout chips (ROCs). In the ROC, an adaptive gain switching pre-amplifier (PRE), a fully differential Correlated-Double-Sampling (CDS) stage, an Analog-to-Digital Converter (ADC) as well as a Static Random-Access Memory (SRAM) capable of storing all the 2700 images in an XFEL.EU bunch train will be implemented. Several prototypes with different designs of the analogue front-end (PRE and CDS) and ADC test structures have been fabricated in UMC-110 nm CMOS technology and their performance has been evaluated. In this paper, the performance of the analogue front-end and ADC will be summarized.

Diffusion-weighted MR imaging findings of kidneys in patients with early phase of obstruction.

PubMed

Bozgeyik, Zulkif; Kocakoc, Ercan; Sonmezgoz, Fitnet

2009-04-01

Diffusion-weighted (DW) magnetic resonance (MR) imaging is an MR technique used to show molecular diffusion. The apparent diffusion coefficient (ADC), as a quantitative parameter calculated from the DW MR images. The purpose of this study is to evaluate the ability of DW MR imaging in early phase of obstruction due to urolithiasis. Twenty-six patients with acute dilatation of the pelvicalyceal system detected by intravenous urography were included in this study. MR imaging was performed using a 1.5 T whole-body superconducting MR scanner. DW imaging can be performed using single-shot spin-echo, echo-planar imaging (EPI) sequences with the following diffusion gradient b values: 100, 600, 1000 s/mm(2). Circular region of interest (ROI) was placed in the renal parenchyma for the measurement of ADC values in the normal and obstructed kidney. For statistical analyses, Paired t test were used. In spite of obstructed kidneys had the lower ADC values compared to normal kidneys, these alterations were statistically insignificant. We did not observe significantly different ADC values of early phase of obstructed kidneys compared to normal kidneys.

Survival in HIV-infected patients after a cancer diagnosis in the cART Era: results of an italian multicenter study.

PubMed

Gotti, Daria; Raffetti, Elena; Albini, Laura; Sighinolfi, Laura; Maggiolo, Franco; Di Filippo, Elisa; Ladisa, Nicoletta; Angarano, Gioacchino; Lapadula, Giuseppe; Pan, Angelo; Esposti, Anna Degli; Fabbiani, Massimiliano; Focà, Emanuele; Scalzini, Alfredo; Donato, Francesco; Quiros-Roldan, Eugenia

2014-01-01

We studied survival and associated risk factors in an Italian nationwide cohort of HIV-infected individuals after an AIDS-defining cancer (ADC) or non-AIDS-defining cancer (NADC) diagnosis in the modern cART era. Multi-center, retrospective, observational study of HIV patients included in the MASTER Italian Cohort with a cancer diagnosis from January 1998 to September 2012. Malignancies were divided into ADC or NADC on the basis of the Centre for Disease Control-1993 classification. Recurrence of cancer and metastases were excluded. Survivals were estimated according to the Kaplan-Meier method and compared according to the log-rank test. Statistically significant variables at univariate analysis were entered in a multivariate Cox regression model. Eight hundred and sixty-six cancer diagnoses were recorded among 13,388 subjects in the MASTER Database after 1998: 435 (51%) were ADCs and 431 (49%) were NADCs. Survival was more favorable after an ADC diagnosis than a NADC diagnosis (10-year survival: 62.7%±2.9% vs. 46%±4.2%; p = 0.017). Non-Hodgkin lymphoma had lower survival rates than patients with Kaposi sarcoma or cervical cancer (10-year survival: 48.2%±4.3% vs. 72.8%±4.0% vs. 78.5%±9.9%; p<0.001). Regarding NADCs, breast cancer showed better survival (10-year survival: 65.1%±14%) than lung cancer (1-year survival: 28%±8.7%), liver cancer (5-year survival: 31.9%±6.4%) or Hodgkin lymphoma (10-year survival: 24.8%±11.2%). Lower CD4+ count and intravenous drug use were significantly associated with decreased survival after ADCs or NADCs diagnosis. Exposure to cART was found to be associated with prolonged survival only in the case of ADCs. cART has improved survival in patients with an ADC diagnosis, whereas the prognosis after a diagnosis of NADCs is poor. Low CD4+ counts and intravenous drug use are risk factors for survival following a diagnosis of ADCs and Hodgkin lymphoma in the NADC group.

Survival in HIV-Infected Patients after a Cancer Diagnosis in the cART Era: Results of an Italian Multicenter Study

PubMed Central

Gotti, Daria; Raffetti, Elena; Albini, Laura; Sighinolfi, Laura; Maggiolo, Franco; Di Filippo, Elisa; Ladisa, Nicoletta; Angarano, Gioacchino; Lapadula, Giuseppe; Pan, Angelo; Esposti, Anna Degli; Fabbiani, Massimiliano; Focà, Emanuele; Scalzini, Alfredo; Donato, Francesco; Quiros-Roldan, Eugenia

2014-01-01

Objectives We studied survival and associated risk factors in an Italian nationwide cohort of HIV-infected individuals after an AIDS-defining cancer (ADC) or non-AIDS-defining cancer (NADC) diagnosis in the modern cART era. Methods Multi-center, retrospective, observational study of HIV patients included in the MASTER Italian Cohort with a cancer diagnosis from January 1998 to September 2012. Malignancies were divided into ADC or NADC on the basis of the Centre for Disease Control-1993 classification. Recurrence of cancer and metastases were excluded. Survivals were estimated according to the Kaplan-Meier method and compared according to the log-rank test. Statistically significant variables at univariate analysis were entered in a multivariate Cox regression model. Results Eight hundred and sixty-six cancer diagnoses were recorded among 13,388 subjects in the MASTER Database after 1998: 435 (51%) were ADCs and 431 (49%) were NADCs. Survival was more favorable after an ADC diagnosis than a NADC diagnosis (10-year survival: 62.7%±2.9% vs. 46%±4.2%; p = 0.017). Non-Hodgkin lymphoma had lower survival rates than patients with Kaposi sarcoma or cervical cancer (10-year survival: 48.2%±4.3% vs. 72.8%±4.0% vs. 78.5%±9.9%; p<0.001). Regarding NADCs, breast cancer showed better survival (10-year survival: 65.1%±14%) than lung cancer (1-year survival: 28%±8.7%), liver cancer (5-year survival: 31.9%±6.4%) or Hodgkin lymphoma (10-year survival: 24.8%±11.2%). Lower CD4+ count and intravenous drug use were significantly associated with decreased survival after ADCs or NADCs diagnosis. Exposure to cART was found to be associated with prolonged survival only in the case of ADCs. Conclusions cART has improved survival in patients with an ADC diagnosis, whereas the prognosis after a diagnosis of NADCs is poor. Low CD4+ counts and intravenous drug use are risk factors for survival following a diagnosis of ADCs and Hodgkin lymphoma in the NADC group. PMID:24760049

Development of Fluorophore-Labeled Thailanstatin Antibody-Drug Conjugates for Cellular Trafficking Studies.

PubMed

Kulkarni, Chethana; Finley, James E; Bessire, Andrew J; Zhong, Xiaotian; Musto, Sylvia; Graziani, Edmund I

2017-04-19

As the antibody-drug conjugate (ADC) field grows increasingly important for cancer treatment, it is vital for researchers to establish a firm understanding of how ADCs function at the molecular level. To gain insight into ADC uptake, trafficking, and catabolism-processes that are critical to ADC efficacy and toxicity-imaging studies have been performed with fluorophore-labeled conjugates. However, such labels may alter the properties and behavior of the ADC under investigation. As an alternative approach, we present here the development of a "clickable" ADC bearing an azide-functionalized linker-payload (LP) poised for "click" reaction with alkyne fluorophores; the azide group represents a significantly smaller structural perturbation to the LP than most fluorophores. Notably, the clickable ADC shows excellent potency in target-expressing cells, whereas the fluorophore-labeled product ADC suffers from a significant loss of activity, underscoring the impact of the label itself on the payload. Live-cell confocal microscopy reveals robust uptake of the clickable ADC, which reacts selectively in situ with a derivatized fluorescent label. Time-course trafficking studies show greater and more rapid net internalization of the ADCs than the parent antibody. More generally, the application of chemical biology tools to the study of ADCs should improve our understanding of how ADCs are processed in biological systems.

Assessment of physical stability of an antibody drug conjugate by higher order structure analysis: impact of thiol- maleimide chemistry.

PubMed

Guo, Jianxin; Kumar, Sandeep; Prashad, Amarnauth; Starkey, Jason; Singh, Satish K

2014-07-01

To provide a systematic biophysical approach towards a better understanding of impact of conjugation chemistry on higher order structure and physical stability of an antibody drug conjugate (ADC). ADC was prepared using thiol-maleimide chemistry. Physical stabilities of ADC and its parent IgG1 mAb were compared using calorimetric, spectroscopic and molecular modeling techniques. ADC and mAb respond differently to thermal stress. Both the melting temperatures and heat capacities are substantially lower for the ADC. Spectroscopic experiments show that ADC and mAb have similar secondary and tertiary structures, but these are more easily destabilized by thermal stress on the ADC indicating reduced conformational stability. Molecular modeling calculations suggest a substantial decrease in the conformational energy of the mAb upon conjugation. The local surface around the conjugation sites also becomes more hydrophobic in the ADC, explaining the lower colloidal stability and greater tendency of the ADC to aggregate. Computational and biophysical analyses of an ADC and its parent mAb have provided insights into impact of conjugation on physical stability and pinpointed reasons behind lower structural stability and increased aggregation propensity of the ADC. This knowledge can be used to design appropriate formulations to stabilize the ADC.

Computing shifts to monitor ATLAS distributed computing infrastructure and operations

NASA Astrophysics Data System (ADS)

Adam, C.; Barberis, D.; Crépé-Renaudin, S.; De, K.; Fassi, F.; Stradling, A.; Svatos, M.; Vartapetian, A.; Wolters, H.

2017-10-01

The ATLAS Distributed Computing (ADC) group established a new Computing Run Coordinator (CRC) shift at the start of LHC Run 2 in 2015. The main goal was to rely on a person with a good overview of the ADC activities to ease the ADC experts’ workload. The CRC shifter keeps track of ADC tasks related to their fields of expertise and responsibility. At the same time, the shifter maintains a global view of the day-to-day operations of the ADC system. During Run 1, this task was accomplished by a person of the expert team called the ADC Manager on Duty (AMOD), a position that was removed during the shutdown period due to the reduced number and availability of ADC experts foreseen for Run 2. The CRC position was proposed to cover some of the AMODs former functions, while allowing more people involved in computing to participate. In this way, CRC shifters help with the training of future ADC experts. The CRC shifters coordinate daily ADC shift operations, including tracking open issues, reporting, and representing ADC in relevant meetings. The CRC also facilitates communication between the ADC experts team and the other ADC shifters. These include the Distributed Analysis Support Team (DAST), which is the first point of contact for addressing all distributed analysis questions, and the ATLAS Distributed Computing Shifters (ADCoS), which check and report problems in central services, sites, Tier-0 export, data transfers and production tasks. Finally, the CRC looks at the level of ADC activities on a weekly or monthly timescale to ensure that ADC resources are used efficiently.

Simultaneous Measurement of T2 and Apparent Diffusion Coefficient (T2+ADC) in the Heart With Motion-Compensated Spin Echo Diffusion-Weighted Imaging

PubMed Central

Aliotta, Eric; Moulin, Kévin; Zhang, Zhaohuan; Ennis, Daniel B.

2018-01-01

Purpose To evaluate a technique for simultaneous quantitative T2 and apparent diffusion coefficient (ADC) mapping in the heart (T2+ADC) using spin echo (SE) diffusion-weighted imaging (DWI). Theory and Methods T2 maps from T2+ADC were compared with single-echo SE in phantoms and with T2-prepared (T2-prep) balanced steady-state free precession (bSSFP) in healthy volunteers. ADC maps from T2+ADC were compared with conventional DWI in phantoms and in vivo. T2+ADC was also demonstrated in a patient with acute myocardial infarction (MI). Results Phantom T2 values from T2+ADC were closer to a single-echo SE reference than T2-prep bSSFP (−2.3 ± 6.0% vs 22.2 ± 16.3%; P < 0.01), and ADC values were in excellent agreement with DWI (0.28 ± 0.4%). In volunteers, myocardial T2 values from T2+ADC were significantly shorter than T2-prep bSSFP (35.8 ± 3.1 vs 46.8 ± 3.8 ms; P < 0.01); myocardial ADC was not significantly (N.S.) different between T2+ADC and conventional motion-compensated DWI (1.39 ± 0.18 vs 1.38 ± 0.18 mm2/ms; P = N.S.). In the patient, T2 and ADC were both significantly elevated in the infarct compared with remote myocardium (T2: 40.4 ± 7.6 vs 56.8 ± 22.0; P < 0.01; ADC: 1.47 ± 0.59 vs 1.65 ± 0.65 mm2/ms; P < 0.01). Conclusion T2+ADC generated coregistered, free-breathing T2 and ADC maps in healthy volunteers and a patient with acute MI with no cost in accuracy, precision, or scan time compared with DWI. PMID:28516485

TORMES-BEXUS 17 and 19: Precursor of the 6U CubeSat 3CAT-2

NASA Astrophysics Data System (ADS)

Carreno-Luengo, H.; Amezaga, A.; Bolet, A.; Vidal, D.; Jane, J.; Munoz, J. F.; Olive, R.; Camps, A.; Carola, J.; Catarino, N.; Hagenfeldt, M.; Palomo, P.; Cornara, S.

2015-09-01

3Cat-2 Assembly, Integration and Verification (AIV) activities of the Engineering Model (EM) and the Flight Model (FM) are being carried out at present. The Attitude Determination and Control System (ADCS) and Flight Software (FSW) validation campaigns will be performed at Universitat Politècnica de Catalunya (UPC) during the incomings months. An analysis and verification of the 3Cat-2 key mission requirements has been performed. The main results are summarized in this work.

Two-step single slope/SAR ADC with error correction for CMOS image sensor.

PubMed

Tang, Fang; Bermak, Amine; Amira, Abbes; Amor Benammar, Mohieddine; He, Debiao; Zhao, Xiaojin

2014-01-01

Conventional two-step ADC for CMOS image sensor requires full resolution noise performance in the first stage single slope ADC, leading to high power consumption and large chip area. This paper presents an 11-bit two-step single slope/successive approximation register (SAR) ADC scheme for CMOS image sensor applications. The first stage single slope ADC generates a 3-bit data and 1 redundant bit. The redundant bit is combined with the following 8-bit SAR ADC output code using a proposed error correction algorithm. Instead of requiring full resolution noise performance, the first stage single slope circuit of the proposed ADC can tolerate up to 3.125% quantization noise. With the proposed error correction mechanism, the power consumption and chip area of the single slope ADC are significantly reduced. The prototype ADC is fabricated using 0.18 μ m CMOS technology. The chip area of the proposed ADC is 7 μ m × 500 μ m. The measurement results show that the energy efficiency figure-of-merit (FOM) of the proposed ADC core is only 125 pJ/sample under 1.4 V power supply and the chip area efficiency is 84 k  μ m(2) · cycles/sample.

Optical-analog-to-digital conversion based on successive-like approximations in octagonal-shape photonic crystal ring resonators

NASA Astrophysics Data System (ADS)

Tavousi, A.; Mansouri-Birjandi, M. A.

2018-02-01

Implementing intensity-dependent Kerr-like nonlinearity in octagonal-shape photonic crystal ring resonators (OSPCRRs), a new class of optical analog-to-digital converters (ADCs) with low power consumption is presented. Due to its size dependent refractive index, Silicon (Si) nanocrystal is used as nonlinear medium in the proposed ADC. Coding system of optical ADC is based on successive-like approximations which requires only one quantization level to represent each single bit, despite of conventional ADCs that require at least two distinct levels for each bit. Each is representing bit of optical ADC is formed by vertically alignment of double rings of OSPCRRs (DR-OSPCRR) and cascading m number of DR-OSPCRR, forms an m bit ADC. Investigating different parameters of DR-OSPCRR such as refractive indices of rings, lattice refractive index, and coupling coefficients of waveguide-to-ring and ring-to-ring, the ADC's threshold power is tuned. Increasing the number of bits of ADC, increases the overall power consumption of ADC. One can arrange to have any number of bits for this ADC, as long as the power levels are treated carefully. Finite difference time domain (FDTD) in-house codes were used to evaluate the ADC's effectiveness.

Preoperative grading of supratentorial nonenhancing gliomas by high b-value diffusion-weighted 3 T magnetic resonance imaging.

PubMed

Han, Haiwei; Han, Chengkun; Wu, Xiurong; Zhong, Shan; Zhuang, Xiongjie; Tan, Guowei; Wu, Hua

2017-05-01

The purpose of this study was to determine the difference in discrimination between high- and low-grade supratentorial nonenhancing gliomas (HGGs and LGGs, respectively) when using apparent diffusion coefficient (ADC) values with high or standard b-value. Thirty-nine patients underwent conventional magnetic resonance imaging and diffusion-weighted imaging (DWI) with standard and high b-values (b = 1000 and 3000 s/mm 2 , respectively). Minimum, maximum, and mean ADC values (ADC MIN , ADC MAX , and ADC MEAN , respectively) were measured from ADC maps with both b-values. Receiver operating curve analysis was used to determine the cutoff ADC values for distinguishing between nonenhancing HGGs and LGGs. ADC MIN , ADC MAX , and ADC MEAN values for the nonenhancing HGGs were lower than those for LGGs. These differences were much larger when a high b-value was used (all P < 0.0001) than when a standard b-value was used (P = 0.0001, <0.0001, and <0.0001, respectively). Discriminant analysis indicated that the greatest likelihood for discriminating HGGs and LGGs when ADC MEAN was obtained with a high b-value, with cutoff value of 0.814 × 10 -3  mm 2 /s. ADC values obtained with a high b-value can be useful for grading and surgical management of nonenhancing HGGs and LGGs. The lowest degree of overlap was obtained when ADC MEAN was determined with a b-value of 3000 s/mm 2 .

Simultaneous Silencing of Two Arginine Decarboxylase Genes Alters Development in Arabidopsis

PubMed Central

Sánchez-Rangel, Diana; Chávez-Martínez, Ana I.; Rodríguez-Hernández, Aída A.; Maruri-López, Israel; Urano, Kaoru; Shinozaki, Kazuo; Jiménez-Bremont, Juan F.

2016-01-01

Polyamines (PAs) are small aliphatic polycations that are found ubiquitously in all organisms. In plants, PAs are involved in diverse biological processes such as growth, development, and stress responses. In Arabidopsis thaliana, the arginine decarboxylase enzymes (ADC1 and 2) catalyze the first step of PA biosynthesis. For a better understanding of PA biological functions, mutants in PA biosynthesis have been generated; however, the double adc1/adc2 mutant is not viable in A. thaliana. In this study, we generated non-lethal A. thaliana lines through an artificial microRNA that simultaneously silenced the two ADC genes (amiR:ADC). The generated transgenic lines (amiR:ADC-L1 and -L2) showed reduced AtADC1 and AtADC2 transcript levels. For further analyses the amiR:ADC-L2 line was selected. We found that the amiR:ADC-L2 line showed a significant decrease of their PA levels. The co-silencing revealed a stunted growth in A. thaliana seedlings, plantlets and delay in its flowering rate; these phenotypes were reverted with PA treatment. In addition, amiR:ADC-L2 plants displayed two seed phenotypes, such as yellow and brownish seeds. The yellow mutant seeds were smaller than adc1, adc2 mutants and wild type seeds; however, the brownish were the smallest seeds with arrested embryos at the torpedo stage. These data reinforce the importance of PA homeostasis in the plant development processes. PMID:27014322

Can Apparent Diffusion Coefficient Values Assist PI-RADS Version 2 DWI Scoring? A Correlation Study Using the PI-RADSv2 and International Society of Urological Pathology Systems.

PubMed

Gaur, Sonia; Harmon, Stephanie; Rosenblum, Lauren; Greer, Matthew D; Mehralivand, Sherif; Coskun, Mehmet; Merino, Maria J; Wood, Bradford J; Shih, Joanna H; Pinto, Peter A; Choyke, Peter L; Turkbey, Baris

2018-05-07

The purposes of this study were to assess correlation of apparent diffusion coefficient (ADC) and normalized ADC (ratio of tumor to nontumor tissue) with the Prostate Imaging Reporting and Data System version 2 (PI-RADSv2) and updated International Society of Urological Pathology (ISUP) categories and to determine how to optimally use ADC metrics for objective assistance in categorizing lesions within PI-RADSv2 guidelines. In this retrospective study, 100 patients (median age, 62 years; range, 44-75 years; prostate-specific antigen level, 7.18 ng/mL; range, 1.70-84.56 ng/mL) underwent 3-T multiparametric MRI of the prostate with an endorectal coil. Mean ADC was extracted from ROIs based on subsequent prostatectomy specimens. Histopathologic analysis revealed 172 lesions (113 peripheral, 59 transition zone). Two radiologists blinded to histopathologic outcome assigned PI-RADSv2 categories. Kendall tau was used to correlate ADC metrics with PI-RADSv2 and ISUP categories. ROC curves were used to assess the utility of ADC metrics in differentiating each reader's PI-RADSv2 DWI category 4 or 5 assessment in the whole prostate and by zone. ADC metrics negatively correlated with ISUP category in the whole prostate (ADC, τ = -0.21, p = 0.0002; normalized ADC, τ = -0.21, p = 0.0001). Moderate negative correlation was found in expert PI-RADSv2 DWI categories (ADC, τ = -0.34; normalized ADC, τ = -0.31; each p < 0.0001) maintained across zones. In the whole prostate, AUCs of ADC and normalized ADC were 87% and 82% for predicting expert PI-RADSv2 DWI category 4 or 5. A derived optimal cutoff ADC less than 1061 and normalized ADC less than 0.65 achieved positive predictive values of 83% and 84% for correct classification of PI-RADSv2 DWI category 4 or 5 by an expert reader. Consistent relations and predictive values were found by an independent novice reader. ADC and normalized ADC inversely correlate with PI-RADSv2 and ISUP categories and can serve as quantitative metrics to assist with assigning PI-RADSv2 DWI category 4 or 5.

Detection of ISAba1 in association with a novel allelic variant of the β-lactamase ADC-82 and class D β-lactamase genes mediating carbapenem resistance among the clinical isolates of MDR A. baumannii.

PubMed

Saranathan, Rajagopalan; Kumari, Rinki; Kalaivani, Ramakrishnan; Suresh, Sah; Rani, Anshu; Purty, Shashikala; Prashanth, K

2017-03-01

The objective of the present study is to investigate the diverse resistance determinants, their association with insertion sequence mobile elements and predilection of a particular clone for such associations in Acinetobacter baumannii. Fifty-four consecutive isolates collected during 2011-2012 from a tertiary care hospital were subjected to susceptibility testing followed by PCR screening of commonly reported β-lactamases and 16S rRNA methyltransferase encoding genes. The integrity of resistance-nodulation-cell division efflux pump-related genes in their respective operons was also investigated. β-Lactamase genes such as blaADC (100 %), blaOXA-23 (81 %), blaPER-1 (81 %), blaIMP-1 (31 %) and blaNDM-1 (15 %) were found to be present more frequently while blaVIM-2 and blaOXA-24 were not observed in our study population. ISAba1 was associated only with blaOXA-51-like like (30 %), blaOXA-23-like (55 %) and blaADC-like (33 %). armA was found in 87 % of isolates and ISAba1 linked with one novel variant of ADC, namely blaADC-82, which was identified to have 15 nucleotide differences with blaADC-79, and this finding is of much significance. In many isolates, efflux pump genes were not intact, resulting in severely altered effluxing functions. For the first time, we have identified ISAba1-mediated disruption of adeN among the isolates of ST 195B, which would have led to overexpression of AdeIJK efflux pump causing elevated resistance. Multilocus sequence typing revealed the predominance of CC 92B (IC-IIB) and CC 447B clonal complexes. High incidence of IC-II clones, novel resistance determinants (ADC-82) and elevated resistance mediated by ISAba1 reported here will be of enormous importance while assessing the emergence of extremely resistant A. baumannii in India.

Apparent diffusion coefficient mapping in medulloblastoma predicts non-infiltrative surgical planes.

PubMed

Marupudi, Neena I; Altinok, Deniz; Goncalves, Luis; Ham, Steven D; Sood, Sandeep

2016-11-01

An appropriate surgical approach for posterior fossa lesions is to start tumor removal from areas with a defined plane to where tumor is infiltrating the brainstem or peduncles. This surgical approach minimizes risk of damage to eloquent areas. Although magnetic resonance imaging (MRI) is the current standard preoperative imaging obtained for diagnosis and surgical planning of pediatric posterior fossa tumors, it offers limited information on the infiltrative planes between tumor and normal structures in patients with medulloblastomas. Because medulloblastomas demonstrate diffusion restriction on apparent diffusion coefficient map (ADC map) sequences, we investigated the role of ADC map in predicting infiltrative and non-infiltrative planes along the brain stem and/or cerebellar peduncles by medulloblastomas prior to surgery. Thirty-four pediatric patients with pathologically confirmed medulloblastomas underwent surgical resection at our facility from 2004 to 2012. An experienced pediatric neuroradiologist reviewed the brain MRIs/ADC map, assessing the planes between the tumor and cerebellar peduncles/brain stem. An independent evaluator documented surgical findings from operative reports for comparison to the radiographic findings. The radiographic findings were statistically compared to the documented intraoperative findings to determine predictive value of the test in identifying tumor infiltration of the brain stem cerebellar peduncles. Twenty-six patients had preoperative ADC mapping completed and thereby, met inclusion criteria. Mean age at time of surgery was 8.3 ± 4.6 years. Positive predictive value of ADC maps to predict tumor invasion of the brain stem and cerebellar peduncles ranged from 69 to 88 %; negative predictive values ranged from 70 to 89 %. Sensitivity approached 93 % while specificity approached 78 %. ADC maps are valuable in predicting the infiltrative and non-infiltrative planes along the tumor and brain stem interface in medulloblastomas. Inclusion and evaluation of ADC maps in preoperative evaluation can assist in surgical resection planning in patients with medulloblastoma.

Maternal Immunization with Chimpanzee Adenovirus Expressing RSV Fusion Protein Protects Against Neonatal RSV Pulmonary Infection

PubMed Central

Sharma, Anurag; Wendland, Rebecca; Sung, Biin; Wu, Wendy; Grunwald, Thomas; Worgall, Stefan

2014-01-01

Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract disease with high morbidity and mortality in young infants and children. Despite numerous efforts, a licensed vaccine against RSV remains elusive. Since young infants form the primary target group of RSV disease, maternal immunization to boost the protection in neonates is an attractive strategy. In this study we tested the efficacy of maternal immunization with a chimpanzee adenovirus expressing codon-optimized RSV fusion protein (AdC7-Fsyn) to protect infants against RSV infection. Single intranasal immunization of mice by AdC7-Fsyn induced robust anti-RSV systemic and mucosal immunity that protected against RSV without causing vaccine-enhanced RSV disease. RSV humoral immunity was transferred to pups born to immunized mothers that provided protection against RSV. Immunization with AdC7-Fsyn was effective even in the presence of Ad5 preimmunity. The maternally derived immunity was durable with the half-life of 14.63 days that reduced the viral replication up to 15 weeks of age. Notably, the passively immunized mice could be actively re-immunized with AdC7-Fsyn to boost and extend the protection. This substantiates maternal immunization with an AdC7-based vaccine expressing RSV F as feasible approach to protect against RSV early in life. PMID:25171847

Diffusion-weighted magnetic resonance imaging with apparent diffusion coefficient (ADC) determination in normal and pathological fetal kidneys.

PubMed

Chaumoitre, K; Colavolpe, N; Shojai, R; Sarran, A; D' Ercole, C; Panuel, M

2007-01-01

To assess the use of diffusion-weighted magnetic resonance imaging (DW-MRI) in the evaluation of the fetal kidney and to estimate age-dependent changes in the apparent diffusion coefficient (ADC) of normal and pathological fetal kidneys. DW-MRI was performed on a 1.5-T machine at 23-38 gestational weeks in 51 pregnant women in whom the fetal kidneys were normal and in 10 whose fetuses had renal pathology (three with suspected nephropathy, three with renal tract dilatation, one with unilateral renal venous thrombosis, and three with twin-twin transfusion syndrome (TTTS)). The ADC was measured in an approximately 1-cm2 region of interest within the renal parenchyma. ADC values in normal renal parenchyma ranged from 1.1 to 1.8 10(-3) mm2 s-1. There was no significant age-dependent change in the ADC of normal kidneys. In cases of nephropathy, the ADC value was not always pathological but an ADC map could show abnormal findings. In cases of dilatation, the ADC value was difficult to determine when the dilatation was huge. In cases of TTTS, the ADC of the donor twin was higher than that of the recipient twin and the difference seemed to be related to the severity of the syndrome. Evaluation of the ADC for fetal kidneys is feasible. Fetal measurement of the ADC value and ADC maps may be useful tools with which to explore the fetal kidney when used in conjunction with current methods. DW-MR images, ADC value and ADC map seem to be useful in cases of suspected nephropathy (hyperechoic kidneys), dilated kidney and vascular pathology (renal venous thrombosis, TTTS). Copyright (c) 2006 ISUOG.

Preoperative grading of supratentorial gliomas using high or standard b-value diffusion-weighted MR imaging at 3T.

PubMed

Cihangiroglu, M M; Ozturk-Isik, E; Firat, Z; Kilickesmez, O; Ulug, A M; Ture, U

2017-03-01

The goal of this study was to compare diffusion-weighted magnetic resonance imaging (DW-MRI) using high b-value (b=3000s/mm 2 ) to DW-MRI using standard b-value (b=1000s/mm 2 ) in the preoperative grading of supratentorial gliomas. Fifty-three patients with glioma had brain DW-MRI at 3T using two different b-values (b=1000s/mm 2 and b=3000s/mm 2 ). There were 35 men and 18 women with a mean age of 40.5±17.1 years (range: 18-79 years). Mean, minimum, maximum, and range of apparent diffusion coefficient (ADC) values for solid tumor ROIs (ADC mean , ADC min , ADC max , and ADC diff ), and the normalized ADC (ADC ratio ) were calculated. A Kruskal-Wallis statistic with Bonferroni correction for multiple comparisons was applied to detect significant ADC parameter differences between tumor grades by including or excluding 19 patients with an oligodendroglioma. Receiver operating characteristic curve analysis was conducted to define appropriate cutoff values for grading gliomas. No differences in ADC derived parameters were found between grade II and grade III gliomas. Mean ADC values using standard b-value were 1.17±0.27×10 -3 mm 2 /s [range: 0.63-1.61], 1.05±0.22×10 -3 mm 2 /s [range: 0.73-1.33], and 0.86±0.23×10 -3 mm 2 /s [range: 0.52-1.46] for grades II, III and IV gliomas, respectively. Using high b-value, mean ADC values were 0.89±0.24×10 -3 mm 2 /s [range: 0.42-1.25], 0.82±0.20×10 -3 mm 2 /s [range: 0.56-1.10], and 0.59±0.17×10 -3 mm 2 /s [range: 0.40-1.01] for grades II, III and IV gliomas, respectively. ADC mean , ADC ratio , ADC max , and ADC min were different between grade II and grade IV gliomas at both standard and high b-values. Differences in ADC mean , ADC max , and ADC diff were found between grade III and grade IV only using high b-value. ADC parameters derived from DW-MRI using a high b-value allows a better differential diagnosis of gliomas, especially for differentiating grades III and IV, than those derived from DW-MRI using a standard b-value. Copyright © 2016 Éditions françaises de radiologie. Published by Elsevier Masson SAS. All rights reserved.

Diffusion tensor imaging assessment of brain white matter maturation during the first postnatal year.

PubMed

Provenzale, James M; Liang, Luxia; DeLong, David; White, Leonard E

2007-08-01

The purpose of this study was to use diffusion-weighted and diffusion tensor imaging to investigate the status of cerebral white matter (WM) at term gestation and the rate of WM maturation throughout the first year of life in healthy infants. Fifty-three children (35 boys) ranging in age from 1.5 weeks premature to 51.5 weeks (mean age, 22.9 weeks) underwent conventional MRI, diffusion imaging in three directions (b = 1,000 s/mm2), and diffusion tensor imaging with gradient encoding in six directions, all on a 1.5-T MRI system. Apparent diffusion coefficient (ADC) and fractional anisotropy (FA) were measured in three deep WM structures (posterior limb of internal capsule, genu, and splenium of corpus callosum) and two peripheral WM regions (associational WM underlying prefrontal and posterior parietal cortex) with a standard region of interest (44 +/- 4 cm2). ADC and FA were expressed as a percentage of corresponding values measured in a group of healthy young adults. Mean ADC and FA values for deep and peripheral WM were plotted against gestational age normalized to term. The data were fit best with a broken-line linear regression model with a breakpoint at 100 days. ADC and FA values at term were estimated according to the intercept of the initial linear period (before day 100) with day 0. The slope of the linear fits was used to determine the rate of WM maturation in both the early and the late (after day 100) periods. Multivariate analysis of variance tests were used to compare deep and peripheral WM structures at term and at representative early and late ages (days 30 and 200) and to compare rates of ADC and FA maturation in early and late periods within the first year. At term, peripheral WM was less mature than deep WM according to results of extrapolation of ADC and FA values in the first 100 days of life to day 0 (p < 0.01). Mean ADC and FA value (percentage of mean adult value) for peripheral WM were 1.32 x 10(-3) mm2/s (163%) and 0.16 (32%), respectively, and 1.09 x 10(-3) mm2/s (143%) and 0.36 (54%), respectively, for deep WM. On day 30 and day 200, estimated mean ADC and FA continued to show greater diffusion (higher ADC) and less anisotropy (lower FA value) in peripheral WM (p <0.01). During the first year of postnatal life, both ADC and FA matured at higher rates before postnatal day 100 compared with a later time. Differences were observed in rates of maturation in the first 100 days when rates of decrease in ADC and increase in FA were compared between peripheral WM and deep WM; however, the maturational trends differed whether ADC or FA was examined. The early rate of ADC decrease (maturation) was twice as great for peripheral WM than for deep WM (p < 0.01) unexpectedly, but the opposite pattern was observed for FA. The early rate of FA increase (maturation) was approximately one half as great for peripheral WM as for deep WM (p = 0.01). Throughout the rest of the first year, no differences were observed in the rates of change in either index between peripheral WM and deep WM. At term, both ADC and FA differ significantly in peripheral WM and deep WM, deep WM structures being more mature. Both deep WM and peripheral WM mature more rapidly during approximately the first 3 months in comparison with the rest of the first year. Unexpected differences in early (first 100 days) rates of maturation assessed with diffusion-weighted (ADC) and diffusion tensor (FA) imaging suggest that these two techniques may be sensitive to different aspects of WM maturation in the early perinatal period.

Method and apparatus for low power analog-to-digital conversion

DOEpatents

De Geronimo, Gianluigi; Nambiar, Neena

2013-10-01

A method and apparatus for analog-to-digital conversion. An Analog-to-Digital Converter (ADC) includes M ADC.sub.j, j=1, 2, . . . , M. Each ADC.sub.j comprises a number of cells each of which comprises a first switch, a second switch, a current sink and an inverter. An inverter of a cell in an ADC.sub.j changes state in response to a current associate with an input signal of the ADC.sub.j exceeding a threshold, thus switching on the next cell. Each ADC.sub.j is enabled to perform analog-to-digital conversion on a residual current of a previous ADC.sub.j-1 after the previous ADC.sub.j-1 has completed its analog-to-digital conversion and has been disabled.

Diagnostic value of ADC in patients with prostate cancer: influence of the choice of b values.

PubMed

Thörmer, Gregor; Otto, Josephin; Reiss-Zimmermann, Martin; Seiwerts, Matthias; Moche, Michael; Garnov, Nikita; Franz, Toni; Do, Minh; Stolzenburg, Jens-Uwe; Horn, Lars-Christian; Kahn, Thomas; Busse, Harald

2012-08-01

To evaluate the influence of the choice of b values on the diagnostic value of the apparent diffusion coefficient (ADC) for detection and grading of prostate cancer (PCa). Forty-one patients with biopsy-proven PCa underwent endorectal 3-T MRI before prostatectomy. Different combinations of b values (0-800 s/mm(2)) were used to calculate four representative ADC maps. Mean ADCs of tumours and non-malignant tissue were determined. Tumour appearance on different ADC maps was rated by three radiologists as good, fair or poor by assigning a visual score (VS) of 2, 1 or 0, respectively. Differences in the ADC values with the choice of b values were analysed using one-way ANOVA. Choice of b values had a highly (P < 0.001) significant influence on the absolute ADC in each tissue. Maps using b = [50, 800] and [0, 800] were rated best (VS= 1.6 ± 0.3) and second best (1.1 ± 0.3, P < 0.001), respectively. For low-grade carcinomas (Gleason score ≤ 6, 13/41 patients), only the former choice received scores better than fair (VS = 1.4 ± 0.3). Mean tumour ADCs showed significant negative correlation (Spearman's ρ -0.38 to -0.46, P < 0.05) with Gleason score. Absolute ADC values strongly depend on the choice of b values and therefore should be used with caution for diagnostic purposes. A minimum b value greater than zero is recommended for ADC calculation to improve the visual assessment of PCa in ADC maps. • Absolute ADC values are highly dependent on the choice of b values. • Absolute ADC thresholds should be used carefully to predict tumour aggressiveness. • Subjective ratings of ADC maps involving b = 0 s/mm ( 2 ) are poor to fair. • Minimum b value greater than 0 s/mm ( 2 ) is recommended for ADC calculation.

Apparent diffusion coefficient for molecular subtyping of non-gadolinium-enhancing WHO grade II/III glioma: volumetric segmentation versus two-dimensional region of interest analysis.

PubMed

Thust, S C; Hassanein, S; Bisdas, S; Rees, J H; Hyare, H; Maynard, J A; Brandner, S; Tur, C; Jäger, H R; Yousry, T A; Mancini, L

2018-03-23

To investigate if quantitative apparent diffusion coefficient (ADC) measurements can predict genetic subtypes of non-gadolinium-enhancing gliomas, comparing whole tumour against single slice analysis. Volumetric T2-derived masks of 44 gliomas were co-registered to ADC maps with ADC mean (ADC mean ) calculated. For the slice analysis, two observers placed regions of interest in the largest tumour cross-section. The ratio (ADC ratio ) between ADC mean in the tumour and normal appearing white matter was calculated for both methods. Isocitrate dehydrogenase (IDH) wild-type gliomas showed the lowest ADC values throughout (p < 0.001). ADC mean in the IDH-mutant 1p19q intact group was significantly higher than in the IDH-mutant 1p19q co-deleted group (p < 0.01). A volumetric ADC mean threshold of 1201 × 10 -6 mm 2 /s identified IDH wild-type with a sensitivity of 83% and a specificity of 86%; a volumetric ADC ratio cut-off value of 1.65 provided a sensitivity of 80% and a specificity of 92% (area under the curve (AUC) 0.9-0.94). A slice ADC ratio threshold for observer 1 (observer 2) of 1.76 (1.83) provided a sensitivity of 80% (86%), specificity of 91% (100%) and AUC of 0.95 (0.96). The intraclass correlation coefficient was excellent (0.98). ADC measurements can support the distinction of glioma subtypes. Volumetric and two-dimensional measurements yielded similar results in this study. • Diffusion-weighted MRI aids the identification of non-gadolinium-enhancing malignant gliomas • ADC measurements may permit non-gadolinium-enhancing glioma molecular subtyping • IDH wild-type gliomas have lower ADC values than IDH-mutant tumours • Single cross-section and volumetric ADC measurements yielded comparable results in this study.

Automated On-tip Affinity Capture Coupled with Mass Spectrometry to Characterize Intact Antibody-Drug Conjugates from Blood

NASA Astrophysics Data System (ADS)

Li, Ke Sherry; Chu, Phillip Y.; Fourie-O'Donohue, Aimee; Srikumar, Neha; Kozak, Katherine R.; Liu, Yichin; Tran, John C.

2018-05-01

Antibody-drug conjugates (ADCs) present unique challenges for ligand-binding assays primarily due to the dynamic changes of the drug-to-antibody ratio (DAR) distribution in vivo and in vitro. Here, an automated on-tip affinity capture platform with subsequent mass spectrometry analysis was developed to accurately characterize the DAR distribution of ADCs from biological matrices. A variety of elution buffers were tested to offer optimal recovery, with trastuzumab serving as a surrogate to the ADCs. High assay repeatability (CV 3%) was achieved for trastuzumab antibody when captured below the maximal binding capacity of 7.5 μg. Efficient on-tip deglycosylation was also demonstrated in 1 h followed by affinity capture. Moreover, this tip-based platform affords higher throughput for DAR characterization when compared with a well-characterized bead-based method.

Histogram analysis of apparent diffusion coefficient maps for differentiating primary CNS lymphomas from tumefactive demyelinating lesions.

PubMed

Lu, Shan Shan; Kim, Sang Joon; Kim, Namkug; Kim, Ho Sung; Choi, Choong Gon; Lim, Young Min

2015-04-01

This study intended to investigate the usefulness of histogram analysis of apparent diffusion coefficient (ADC) maps for discriminating primary CNS lymphomas (PCNSLs), especially atypical PCNSLs, from tumefactive demyelinating lesions (TDLs). Forty-seven patients with PCNSLs and 18 with TDLs were enrolled in our study. Hyperintense lesions seen on T2-weighted images were defined as ROIs after ADC maps were registered to the corresponding T2-weighted image. ADC histograms were calculated from the ROIs containing the entire lesion on every section and on a voxel-by-voxel basis. The ADC histogram parameters were compared among all PCNSLs and TDLs as well as between the subgroup of atypical PCNSLs and TDLs. ROC curves were constructed to evaluate the diagnostic performance of the histogram parameters and to determine the optimum thresholds. The differences between the PCNSLs and TDLs were found in the minimum ADC values (ADCmin) and in the 5th and 10th percentiles (ADC5% and ADC10%) of the cumulative ADC histograms. However, no statistical significance was found in the mean ADC value or in the ADC value concerning the mode, kurtosis, and skewness. The ADCmin, ADC5%, and ADC10% were also lower in atypical PCNSLs than in TDLs. ADCmin was the best indicator for discriminating atypical PCNSLs from TDLs, with a threshold of 556×10(-6) mm2/s (sensitivity, 81.3 %; specificity, 88.9%). Histogram analysis of ADC maps may help to discriminate PCNSLs from TDLs and may be particularly useful in differentiating atypical PCNSLs from TDLs.

Comparison of bi-exponential and mono-exponential models of diffusion-weighted imaging for detecting active sacroiliitis in ankylosing spondylitis.

PubMed

Sun, Haitao; Liu, Kai; Liu, Hao; Ji, Zongfei; Yan, Yan; Jiang, Lindi; Zhou, Jianjun

2018-04-01

Background There has been a growing need for a sensitive and effective imaging method for the differentiation of the activity of ankylosing spondylitis (AS). Purpose To compare the performances of intravoxel incoherent motion (IVIM)-derived parameters and the apparent diffusion coefficient (ADC) for distinguishing AS-activity. Material and Methods One hundred patients with AS were divided into active (n = 51) and non-active groups (n = 49) and 21 healthy volunteers were included as control. The ADC, diffusion coefficient ( D), pseudodiffusion coefficient ( D*), and perfusion fraction ( f) were calculated for all groups. Kruskal-Wallis tests and receiver operator characteristic (ROC) curve analysis were performed for all parameters. Results There was good reproducibility of ADC /D and relatively poor reproducibility of D*/f. ADC, D, and f were significantly higher in the active group than in the non-active and control groups (all P < 0.0001, respectively). D* was slightly but significant lower in the active group than in the non-active and control group ( P = 0.0064, 0.0215). There was no significant difference in any parameter between the non-active group and the control group (all P > 0.050). In the ROC analysis, ADC had the largest AUC for distinguishing between the active group and the non-active group (0.988) and between the active and control groups (0.990). Multivariate logistic regression analysis models showed no diagnostic improvement. Conclusion ADC provided better diagnostic performance than IVIM-derived parameters in differentiating AS activity. Therefore, a straightforward and effective mono-exponential model of diffusion-weighted imaging may be sufficient for differentiating AS activity in the clinic.

Feasibility of Intravoxel Incoherent Motion for Differentiating Benign and Malignant Thyroid Nodules.

PubMed

Tan, Hui; Chen, Jun; Zhao, Yi Ling; Liu, Jin Huan; Zhang, Liang; Liu, Chang Sheng; Huang, Dongjie

2018-06-13

This study aimed to preliminarily investigate the feasibility of intravoxel incoherent motion (IVIM) theory in the differential diagnosis of benign and malignant thyroid nodules. Forty-five patients with 56 confirmed thyroid nodules underwent preoperative routine magnetic resonance imaging and IVIM diffusion-weighted imaging. The histopathologic diagnosis was confirmed by surgery. Apparent diffusion coefficient (ADC), perfusion fraction f, diffusivity D, and pseudo-diffusivity D* were quantified. Independent samples t test of IVIM-derived metrics were conducted between benign and malignant nodules. Receiver-operating characteristic analyses were performed to determine the optimal thresholds as well as the sensitivity and specificity for differentiating. Significant intergroup difference was observed in ADC, D, D*, and f (p < 0.001). Malignant tumors featured significantly lower ADC, D and D* values and a higher f value than that of benign nodules. The ADC, D, and D* could distinguish the benign from malignant thyroid nodules, and parameter f differentiate the malignant tumors from benign nodules. The values of the area under the curve for parameter ADC, D, and D* were 0.784 (p = 0.001), 0.795 (p = 0.001), and 0.850 (p < 0.001), separately, of which the area under the curve of f value was the maximum for identifying the malignant from benign nodules, which was 0.841 (p < 0.001). This study suggested that ADC and IVIM-derived metrics, including D, D*, and f, could potentially serve as noninvasive predictors for the preoperative differentiating of thyroid nodules, and f value performed best in identifying the malignant from benign nodules among these parameters. Copyright © 2018 Academic Radiology. Published by Elsevier Inc. All rights reserved.

Physiological Background of Differences in Quantitative Diffusion-Weighted Magnetic Resonance Imaging Between Acute Malignant and Benign Vertebral Body Fractures: Correlation of Apparent Diffusion Coefficient With Quantitative Perfusion Magnetic Resonance Imaging Using the 2-Compartment Exchange Model.

PubMed

Geith, Tobias; Biffar, Andreas; Schmidt, Gerwin; Sourbron, Steven; Dietrich, Olaf; Reiser, Maximilian; Baur-Melnyk, Andrea

2015-01-01

To test the hypothesis that apparent diffusion coefficient (ADC) in vertebral bone marrow of benign and malignant fractures is related to the volume of the interstitial space, determined with dynamic contrast-enhanced (DCE) magnetic resonance imaging. Patients with acute benign (n = 24) and malignant (n = 19) vertebral body fractures were examined at 1.5 T. A diffusion-weighted single-shot turbo-spin-echo sequence (b = 100 to 600 s/mm) and DCE turbo-FLASH sequence were evaluated. Regions of interest were manually selected for each fracture. Apparent diffusion coefficient was determined with a monoexponential decay model. The DCE magnetic resonance imaging concentration-time curves were analyzed using a 2-compartment tracer-kinetic model. Apparent diffusion coefficient showed a significant positive correlation with interstitial volume in the whole study population (Pearson r = 0.66, P < 0.001), as well as in the malignant (Pearson r = 0.64, P = 0.004) and benign (Pearson r = 0.52, P = 0.01) subgroup. A significant correlation between ADC and the permeability-surface area product could be observed when analyzing the whole study population (Spearman rs = 0.40, P = 0.008), but not when separately examining the subgroups. Plasma flow showed a significant correlation with ADC in benign fractures (Pearson r = 0.23, P = 0.03). Plasma volume did not show significant correlations with ADC. The results support the hypothesis that the ADC of a lesion is inversely correlated to its cellularity. This explains previous observations that ADC is reduced in more malignant lesions.

Non-invasive quantification of tumour heterogeneity in water diffusivity to differentiate malignant from benign tissues of urinary bladder: a phase I study.

PubMed

Nguyen, Huyen T; Shah, Zarine K; Mortazavi, Amir; Pohar, Kamal S; Wei, Lai; Jia, Guang; Zynger, Debra L; Knopp, Michael V

2017-05-01

To quantify the heterogeneity of the tumour apparent diffusion coefficient (ADC) using voxel-based analysis to differentiate malignancy from benign wall thickening of the urinary bladder. Nineteen patients with histopathological findings of their cystectomy specimen were included. A data set of voxel-based ADC values was acquired for each patient's lesion. Histogram analysis was performed on each data set to calculate uniformity (U) and entropy (E). The k-means clustering of the voxel-wised ADC data set was implemented to measure mean intra-cluster distance (MICD) and largest inter-cluster distance (LICD). Subsequently, U, E, MICD, and LICD for malignant tumours were compared with those for benign lesions using a two-sample t-test. Eleven patients had pathological confirmation of malignancy and eight with benign wall thickening. Histogram analysis showed that malignant tumours had a significantly higher degree of ADC heterogeneity with lower U (P = 0.016) and higher E (P = 0.005) than benign lesions. In agreement with these findings, k-means clustering of voxel-wise ADC indicated that bladder malignancy presented with significantly higher MICD (P < 0.001) and higher LICD (P = 0.002) than benign wall thickening. The quantitative assessment of tumour diffusion heterogeneity using voxel-based ADC analysis has the potential to become a non-invasive tool to distinguish malignant from benign tissues of urinary bladder cancer. • Heterogeneity is an intrinsic characteristic of tumoral tissue. • Non-invasive quantification of tumour heterogeneity can provide adjunctive information to improve cancer diagnosis accuracy. • Histogram analysis and k-means clustering can quantify tumour diffusion heterogeneity. • The quantification helps differentiate malignant from benign urinary bladder tissue.

Differential cyclooxygenase-2 expression in squamous cell carcinoma and adenocarcinoma of the uterine cervix.

PubMed

Kim, Yong Bae; Kim, Gwi Eon; Pyo, Hong Ryull; Cho, Nam Hoon; Keum, Ki Chang; Lee, Chang Geol; Seong, Jinsil; Suh, Chang Ok; Park, Tchan Kyu

2004-11-01

To determine the differential expression of cyclooxygenase-2 (COX-2) in patients with squamous cell carcinoma (SCC) and adenocarcinoma (ADC) of the uterine cervix and the prognostic significance of COX-2 expression in these histologic types. A total of 105 International Federation of Gynecology and Obstetrics Stage IIB uterine cervical cancer patients were screened for COX-2 expression immunohistochemically. COX-2 expression was determined in invasive cervical SCC (n = 84) and invasive cervical ADC (n = 21). To determine the clinical significance of COX-2 expression by histologic type, the patients were arbitrarily divided into four groups: SCC/COX-2 negative (n = 64); SCC/COX-2 positive (n = 20); ADC/COX-2 negative (n = 9); and ADC/COX-2 positive (n = 12). The clinical response to treatment, patterns of treatment failure, and survival data by COX-2 expression were compared for these two major histologic types. Univariate and multivariate analyses were performed to identify the prognostic factors influencing survival. Immunohistochemical examination showed that COX-2 expression was more frequently observed in ADC than in SCC (57% vs. 24%, p = 0.007). Moreover, COX-2 expression was an important predictor of treatment response, irrespective of the histologic type. All COX-2-negative patients achieved complete remission after initial treatment; 17% of SCC patients and 33% of ADC patients with COX-2 expression did not have complete remission after the initial treatment. The incidence of local failure for those with COX-2 expression was significantly greater than for COX-2-negative patients, regardless of histologic type. With a minimal follow-up of 60 months, the overall 5-year actuarial survival rate for SCC and ADC patients was 79% and 62%, respectively (p = 0.05). The 5-year disease-free survival rate for SCC and ADC patients was 73% and 56%, respectively (p = 0.13). Irrespective of the pathologic type, COX-2-positive patients had an unfavorable prognosis. The overall 5-year actuarial survival rate was 57% for COX-2-positive patients and 83% for COX-2-negative patients (p = 0.001). When patients were stratified into the four groups according to histologic type and COX-2 expression status, ADC/COX-2-positive patients had the worst prognosis, with an overall 5-year actuarial survival rate of 49% compared with 78% for ADC/COX-2-negative patients, 62% for SCC/COX-2-positive, and 84% for SCC/COX-2-negative patients (p = 0.007, log-rank test). Irrespective of histologic type, COX-2 expression was an independent prognostic factor by univariate and multivariate analyses. In uterine cervical cancer, COX-2 was expressed in a greater proportion of ADC patients than SCC patients. COX-2 expression was also identified as a major determiner of a poor response to treatment and of an unfavorable prognosis, irrespective of the histologic type, reflecting the importance of the COX-2 protein in the acquisition of biologic aggressiveness and more malignant phenotype or increased resistance to the standard chemotherapy and radiotherapy in both histologic types. Given these observations, we believe that that ADC/COX-2-positive patients might be appropriate candidates for future trials of selective COX-2 inhibitor adjunctive therapy.

Optimization of an FPGA Trigger Based on an Artificial Neural Network for the Detection of Neutrino-Induced Air Showers

NASA Astrophysics Data System (ADS)

Szadkowski, Zbigniew; Głas, Dariusz; Pytel, Krzysztof; Wiedeński, Michał

2017-06-01

Neutrinos play a fundamental role in the understanding of the origin of ultrahigh-energy cosmic rays. They interact through charged and neutral currents in the atmosphere generating extensive air showers. However, the very low rate of events potentially generated by neutrinos is a significant challenge for detection techniques and requires both sophisticated algorithms and high-resolution hardware. Air showers initiated by protons and muon neutrinos at various altitudes, angles, and energies were simulated in CORSIKA and the Auger OffLine event reconstruction platforms, giving analog-to-digital convertor (ADC) patterns in Auger water Cherenkov detectors on the ground. The proton interaction cross section is high, so proton “old” showers start their development early in the atmosphere. In contrast to this, neutrinos can generate “young” showers deeply in the atmosphere relatively close to the detectors. Differences between “old” proton and “young” neutrino showers are visible in attenuation factors of ADC waveforms. For the separation of “old” proton and “young” neutrino ADC traces, many three-layer artificial neural networks (ANNs) were tested. They were trained in MATLAB (in a dedicated way -only “old” proton and “young” neutrino showers as patterns) by simulated ADC traces according to the Levenberg-Marquardt algorithm. Unexpectedly, the recognition efficiency is found to be almost independent of the size of the networks. The ANN trigger based on a selected 8-6-1 network was tested in the Cyclone V E FPGA 5CEFA9F31I7, the heart of prototype front-end boards developed for testing new algorithms in the Pierre Auger surface detectors.

Whole-body diffusion kurtosis imaging: initial experience on non-Gaussian diffusion in various organs.

PubMed

Filli, Lukas; Wurnig, Moritz; Nanz, Daniel; Luechinger, Roger; Kenkel, David; Boss, Andreas

2014-12-01

Diffusion kurtosis imaging (DKI) is based on a non-Gaussian diffusion model that should inherently better account for restricted water diffusion within the complex microstructure of most tissues than the conventional diffusion-weighted imaging (DWI), which presumes Gaussian distributed water molecule displacement probability. The aim of this investigation was to test the technical feasibility of in vivo whole-body DKI, probe for organ-specific differences, and compare whole-body DKI and DWI results. Eight healthy subjects underwent whole-body DWI on a clinical 3.0 T magnetic resonance imaging system. Echo-planar images in the axial orientation were acquired at b-values of 0, 150, 300, 500, and 800 mm²/s. Parametrical whole-body maps of the diffusion coefficient (D), the kurtosis (K), and the traditional apparent diffusion coefficient (ADC) were generated. Goodness of fit was compared between DKI and DWI fits using the sums of squared residuals. Data groups were tested for significant differences of the mean by paired Student t tests. Good-quality parametrical whole-body maps of D, K, and ADC could be computed. Compared with ADC values, D values were significantly higher in the cerebral gray matter (by 30%) and white matter (27%), renal cortex (23%) and medulla (21%), spleen (101%), as well as erector spinae muscle (34%) (each P value <0.001). No significant differences between D and ADC were found in the cerebrospinal fluid (P = 0.08) and in the liver (P = 0.13). Curves of DKI fitted the measurement points significantly better than DWI curves did in most organs. Whole-body DKI is technically feasible and may reflect tissue microstructure more meaningfully than whole-body DWI.

Role of intravoxel incoherent motion MR imaging in preoperative assessing HER2 status of gastric cancers.

PubMed

Ji, Changfeng; Zhang, Qinglei; Guan, Wenxian; Guo, Tingting; Chen, Ling; Liu, Song; He, Jian; Zhou, Zhengyang

2017-07-25

To explore the role of intravoxel incoherent motion (IVIM) magnetic resonance (MR) imaging in evaluating human epidermal growth factor receptor 2 (HER2) status of gastric cancers preoperatively. The apparent diffusion coefficient (ADC) and pure diffusion coefficient (D) values correlated positively with HER2 scores of gastric cancers significantly (r = 0.276, P = 0.048; r = 0.481, P < 0.001, respectively). The ADC and D values of HER2 positive gastric cancers were significantly higher than those of HER2 negative tumors (P = 0.033, 0.007, respectively). With a cut-off value of 1.321 and 1.123 × 10-3 mm2/sec, the ADC and D values could distinguish HER2 positive gastric cancers from HER2 negative ones with an area under the curve of 0.733 and 0.762, respectively (P = 0.023, 0.011, respectively). Fifty-three patients with gastric cancers underwent IVIM MR imaging preoperatively. The values of ADC, D, pseudo diffusion coefficient (D*) and perfusion related fraction (f) of the lesions were obtained. Partial correlation test including tumor volume was performed to analyze correlations between IVIM values and HER2 scores excluding the impact of tumor size. IVIM parameters of gastric cancers with different HER2 status were compared using independent samples t test. Diagnostic performance of IVIM parameters in distinguishing HER2 positive gastric cancers from negative ones was tested with receiver operating characteristic analysis. We confirmed the feasibility of IVIM MR imaging in preoperative assessment of HER2 status of gastric cancers, which might make up the shortfall of biopsy and facilitate personalized treatment for patients with gastric cancers.

Configurable analog-digital conversion using the neural engineering framework

PubMed Central

Mayr, Christian G.; Partzsch, Johannes; Noack, Marko; Schüffny, Rene

2014-01-01

Efficient Analog-Digital Converters (ADC) are one of the mainstays of mixed-signal integrated circuit design. Besides the conventional ADCs used in mainstream ICs, there have been various attempts in the past to utilize neuromorphic networks to accomplish an efficient crossing between analog and digital domains, i.e., to build neurally inspired ADCs. Generally, these have suffered from the same problems as conventional ADCs, that is they require high-precision, handcrafted analog circuits and are thus not technology portable. In this paper, we present an ADC based on the Neural Engineering Framework (NEF). It carries out a large fraction of the overall ADC process in the digital domain, i.e., it is easily portable across technologies. The analog-digital conversion takes full advantage of the high degree of parallelism inherent in neuromorphic networks, making for a very scalable ADC. In addition, it has a number of features not commonly found in conventional ADCs, such as a runtime reconfigurability of the ADC sampling rate, resolution and transfer characteristic. PMID:25100933

Different histological subtypes of peripheral lung cancer based on emphysema distribution in patients with both airflow limitation and CT-determined emphysema.

PubMed

Shin, Beomsu; Shin, Sumin; Chung, Myung Jin; Lee, Hyun; Koh, Won-Jung; Kim, Hojoong; Park, Hye Yun

2017-02-01

The histological subtypes by peripheral tumor location remain uncharacterized in COPD patients with emphysema. We investigated histologic subtypes of peripheral lung cancers based on the context of heterogeneous emphysema distribution in patients with airflow limitation and CT-determined emphysema. A retrospective, cross-sectional study was conducted using data from 754 patients with airflow limitation and newly-diagnosed primary lung cancers from February 2013 to February 2015. Of these, 230 patients had emphysema, as determined by computed tomography software designed to quantify emphysema. Among the 230 patients, the most common subtype in central lesions (n=84) was squamous cell carcinoma (SCC) (n=64/84, 76%). Adenocarcinoma (ADC) was more frequently observed in peripheral lesions (n=146) than central lesions (58/146 [40%] vs. 4/84 [5%], p<0.001). In peripheral lesions, ADC was more frequently seen in areas without emphysema than emphysema areas (43/74 [58%] vs. 15/72 [21%], p<0.001), while SCC was more frequently found in emphysema areas than areas without emphysema (44/72 [61%] vs. 13/74 [18%], p<0.001). These associations persisted with adjustments for age, sex, smoking status and forced expiratory volume in 1s. In patients with both airflow limitation and CT-determined emphysema, the main histological subtype of peripheral lung cancer was SCC in emphysema areas and ADC in areas without emphysema. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Increasing the Accuracy of Volume and ADC Delineation for Heterogeneous Tumor on Diffusion-Weighted MRI: Correlation with PET/CT

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

Gong, Nan-Jie; Wong, Chun-Sing, E-mail: drcswong@gmail.com; Chu, Yiu-Ching

2013-10-01

Purpose: To improve the accuracy of volume and apparent diffusion coefficient (ADC) measurements in diffusion-weighted magnetic resonance imaging (MRI), we proposed a method based on thresholding both the b0 images and the ADC maps. Methods and Materials: In 21 heterogeneous lesions from patients with metastatic gastrointestinal stromal tumors (GIST), gross lesion were manually contoured, and corresponding volumes and ADCs were denoted as gross tumor volume (GTV) and gross ADC (ADC{sub g}), respectively. Using a k-means clustering algorithm, the probable high-cellularity tumor tissues were selected based on b0 images and ADC maps. ADC and volume of the tissues selected using themore » proposed method were denoted as thresholded ADC (ADC{sub thr}) and high-cellularity tumor volume (HCTV), respectively. The metabolic tumor volume (MTV) in positron emission tomography (PET)/computed tomography (CT) was measured using 40% maximum standard uptake value (SUV{sub max}) as the lower threshold, and corresponding mean SUV (SUV{sub mean}) was also measured. Results: HCTV had excellent concordance with MTV according to Pearson's correlation (r=0.984, P<.001) and linear regression (slope = 1.085, intercept = −4.731). In contrast, GTV overestimated the volume and differed significantly from MTV (P=.005). ADC{sub thr} correlated significantly and strongly with SUV{sub mean} (r=−0.807, P<.001) and SUV{sub max} (r=−0.843, P<.001); both were stronger than those of ADC{sub g}. Conclusions: The proposed lesion-adaptive semiautomatic method can help segment high-cellularity tissues that match hypermetabolic tissues in PET/CT and enables more accurate volume and ADC delineation on diffusion-weighted MR images of GIST.« less

Internalization, Trafficking, Intracellular Processing and Actions of Antibody-Drug Conjugates.

PubMed

Xu, Shi

2015-11-01

This review discusses the molecular mechanism involved in the targeting and delivery of antibody-drug conjugates (ADCs), the new class of biopharmaceuticals mainly designed for targeted cancer therapy. this review goes over major progress in preclinical and clinical studies of ADCs, in the past 5 years. The pharmacokinetics and pharmacodynamics of ADCs involve multiple mechanisms, including internalization of ADCs by target cells, intracellular trafficking, release of conjugated drugs, and payload. These mechanisms actually jointly determine the efficacy of ADCs. Therefore, the optimization of ADCs should take them as necessary rationales.

In Vitro and In Vivo Evaluation of Cysteine and Site Specific Conjugated Herceptin Antibody-Drug Conjugates

PubMed Central

Jackson, Dowdy; Atkinson, John; Guevara, Claudia I.; Zhang, Chunying; Kery, Vladimir; Moon, Sung-Ju; Virata, Cyrus; Yang, Peng; Lowe, Christine; Pinkstaff, Jason; Cho, Ho; Knudsen, Nick; Manibusan, Anthony; Tian, Feng; Sun, Ying; Lu, Yingchun; Sellers, Aaron; Jia, Xiao-Chi; Joseph, Ingrid; Anand, Banmeet; Morrison, Kendall; Pereira, Daniel S.; Stover, David

2014-01-01

Antibody drug conjugates (ADCs) are monoclonal antibodies designed to deliver a cytotoxic drug selectively to antigen expressing cells. Several components of an ADC including the selection of the antibody, the linker, the cytotoxic drug payload and the site of attachment used to attach the drug to the antibody are critical to the activity and development of the ADC. The cytotoxic drugs or payloads used to make ADCs are typically conjugated to the antibody through cysteine or lysine residues. This results in ADCs that have a heterogeneous number of drugs per antibody. The number of drugs per antibody commonly referred to as the drug to antibody ratio (DAR), can vary between 0 and 8 drugs for a IgG1 antibody. Antibodies with 0 drugs are ineffective and compete with the ADC for binding to the antigen expressing cells. Antibodies with 8 drugs per antibody have reduced in vivo stability, which may contribute to non target related toxicities. In these studies we incorporated a non-natural amino acid, para acetyl phenylalanine, at two unique sites within an antibody against Her2/neu. We covalently attached a cytotoxic drug to these sites to form an ADC which contains two drugs per antibody. We report the results from the first direct preclinical comparison of a site specific non-natural amino acid anti-Her2 ADC and a cysteine conjugated anti-Her2 ADC. We report that the site specific non-natural amino acid anti-Her2 ADCs have superior in vitro serum stability and preclinical toxicology profile in rats as compared to the cysteine conjugated anti-Her2 ADCs. We also demonstrate that the site specific non-natural amino acid anti-Her2 ADCs maintain their in vitro potency and in vivo efficacy against Her2 expressing human tumor cell lines. Our data suggests that site specific non-natural amino acid ADCs may have a superior therapeutic window than cysteine conjugated ADCs. PMID:24454709

Diffusion-weighted MR imaging of upper abdominal organs at different time points: Apparent diffusion coefficient normalization using a reference organ.

PubMed

Song, Ji Soo; Kwak, Hyo Sung; Byon, Jung Hee; Jin, Gong Yong

2017-05-01

To compare the apparent diffusion coefficient (ADC) of upper abdominal organs acquired at different time points, and to investigate the usefulness of normalization. We retrospectively evaluated 58 patients who underwent three rounds of magnetic resonance (MR) imaging including diffusion-weighted imaging of the upper abdomen. MR examinations were performed using three different 3.0 Tesla (T) and one 1.5T systems, with variable b value combinations and respiratory motion compensation techniques. The ADC values of the upper abdominal organs from three different time points were analyzed, using the ADC values of the paraspinal muscle (ADC psm ) and spleen (ADC spleen ) for normalization. Intraclass correlation coefficients (ICC) and comparison of dependent ICCs were used for statistical analysis. The ICCs of the original ADC and ADC psm showed fair to substantial agreement, while ADC spleen showed substantial to almost perfect agreement. The ICC of ADC spleen of all anatomical regions showed less variability compared with that of the original ADC (P < 0.005). Normalized ADC using the spleen as a reference organ significantly decreased variability in measurement of the upper abdominal organs in different MR systems at different time points and could be regarded as an imaging biomarker for future multicenter, longitudinal studies. 5 J. MAGN. RESON. IMAGING 2017;45:1494-1501. © 2016 International Society for Magnetic Resonance in Medicine.

Cerebral schistosomiasis: diffusion-weighted imaging helps to differentiate from brain glioma and metastasis.

PubMed

Huang, Jinbai; Luo, Jing; Peng, Jie; Yang, Tao; Zheng, Huanghua; Mao, Chunping

2017-11-01

Background Diffusion-weighted imaging (DWI) was introduced into clinical use some years ago. However, its use in the diagnosis of cerebral schistosomiasis has not been reported. Purpose To investigate the ability of the apparent diffusion coefficient (ADC) value of DWI in the diagnosis of cerebral schistosomiasis, and to differentiate it from brain high-grade gliomas and metastasis. Material and Methods Conventional brain MRI with pre-contrast, post-contrast, and DWI was performed on 50 cases of cerebral schistosomiasis, high-grade glioma, and brain metastasis. The ADC values of the three lesions, the proximal and the distal perifocal edema were measured. In order to remove the individual difference effect of ADC values, relative ADC (rADC) values were calculated through dividing the ADC value of the lesion area by that of the contralateral normal white matter. rADC values were used to evaluate the differences among cerebral schistosomiasis, brain high-grade gliomas, and metastasis. Results rADC of cerebral schistosomiasis was significantly lower than rADC of brain metastasis ( P < 0.05), without any significant differences when compared with high-grade gliomas. rADC of proximal perifocal edema in cerebral schistosomiasis was significantly higher than in high-grade gliomas ( P < 0.010), but not different compared with brain metastasis. Conclusion DWI examination with ADC values of lesions and proximal perifocal edema might be helpful in the exact diagnosis of cerebral schistosomiasis.

PET/MR in invasive ductal breast cancer: correlation between imaging markers and histological phenotype.

PubMed

Catalano, Onofrio Antonio; Horn, Gary Lloyd; Signore, Alberto; Iannace, Carlo; Lepore, Maria; Vangel, Mark; Luongo, Angelo; Catalano, Marco; Lehman, Constance; Salvatore, Marco; Soricelli, Andrea; Catana, Ciprian; Mahmood, Umar; Rosen, Bruce Robert

2017-03-28

Differences in genetics and receptor expression (phenotypes) of invasive ductal breast cancer (IDC) impact on prognosis and treatment response. Immunohistochemistry (IHC), the most used technique for IDC phenotyping, has some limitations including its invasiveness. We explored the possibility of contrast-enhanced positron emission tomography magnetic resonance (CE-FDG PET/MR) to discriminate IDC phenotypes. 21 IDC patients with IHC assessment of oestrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor-2 (HER2), and antigen Ki-67 (Ki67) underwent CE-FDG PET/MR. Magnetic resonance-perfusion biomarkers, apparent diffusion coefficient (ADC), and standard uptake value (SUV) were compared with IHC markers and phenotypes, using a Student's t-test and one-way ANOVA. ER/PR- tumours demonstrated higher Kep mean and SUV max than ER or PR+ tumours. HER2- tumours displayed higher ADC mean , Kep mean , and SUV max than HER2+tumours. Only ADC mean discriminated Ki67⩽14% tumours (lower ADC mean ) from Ki67>14% tumours. PET/MR biomarkers correlated with IHC phenotype in 13 out of 21 patients (62%; P=0.001). Positron emission tomography magnetic resonance might non-invasively help discriminate IDC phenotypes, helping to optimise individual therapy options.

Continuous Time Level Crossing Sampling ADC for Bio-Potential Recording Systems

PubMed Central

Tang, Wei; Osman, Ahmad; Kim, Dongsoo; Goldstein, Brian; Huang, Chenxi; Martini, Berin; Pieribone, Vincent A.

2013-01-01

In this paper we present a fixed window level crossing sampling analog to digital convertor for bio-potential recording sensors. This is the first proposed and fully implemented fixed window level crossing ADC without local DACs and clocks. The circuit is designed to reduce data size, power, and silicon area in future wireless neurophysiological sensor systems. We built a testing system to measure bio-potential signals and used it to evaluate the performance of the circuit. The bio-potential amplifier offers a gain of 53 dB within a bandwidth of 200 Hz-20 kHz. The input-referred rms noise is 2.8 µV. In the asynchronous level crossing ADC, the minimum delta resolution is 4 mV. The input signal frequency of the ADC is up to 5 kHz. The system was fabricated using the AMI 0.5 µm CMOS process. The chip size is 1.5 mm by 1.5 mm. The power consumption of the 4-channel system from a 3.3 V supply is 118.8 µW in the static state and 501.6 µW with a 240 kS/s sampling rate. The conversion efficiency is 1.6 nJ/conversion. PMID:24163640

Estimate of the global burden of cervical adenocarcinoma and potential impact of prophylactic human papillomavirus vaccination

PubMed Central

2013-01-01

Background Data on the current burden of adenocarcinoma (ADC) and histology-specific human papillomavirus (HPV) type distribution are relevant to predict the future impact of prophylactic HPV vaccines. Methods We estimate the proportion of ADC in invasive cervical cancer, the global number of cases of cervical ADC in 2015, the effect of cervical screening on ADC, the number of ADC cases attributable to high-risk HPV types -16, -18, -45, -31 and -33, and the potential impact of HPV vaccination using a variety of data sources including: GLOBOCAN 2008, Cancer Incidence in Five Continents (CI5) Volume IX, cervical screening data from the World Health Organization/Institut Català d'Oncologia Information Centre on HPV and cervical cancer, and published literature. Results ADC represents 9.4% of all ICC although its contribution varies greatly by country and region. The global crude incidence rate of cervical ADC in 2015 is estimated at 1.6 cases per 100,000 women, and the projected worldwide incidence of ADC in 2015 is 56,805 new cases. Current detection rates for HPV DNA in cervical ADC tend to range around 80–85%; the lower HPV detection rates in cervical ADC versus squamous cell carcinoma may be due to technical artefacts or to misdiagnosis of endometrial carcinoma as cervical ADC. Published data indicate that the five most common HPV types found in cervical ADC are HPV-16 (41.6%), -18 (38.7%), -45 (7.0%), -31 (2.2%) and -33 (2.1%), together comprising 92% of all HPV positive cases. Future projections using 2015 data, assuming 100% vaccine coverage and a true HPV causal relation of 100%, suggest that vaccines providing protection against HPV-16/18 may theoretically prevent 79% of new HPV-related ADC cases (44,702 cases annually) and vaccines additionally providing cross-protection against HPV-31/33/45 may prevent 89% of new HPV-related ADC cases (50,769 cases annually). Conclusions It is predicted that the currently available HPV vaccines will be highly effective in preventing HPV-related cervical ADC. PMID:24261839

Diffusion-weighted imaging of breast lesions: Region-of-interest placement and different ADC parameters influence apparent diffusion coefficient values.

PubMed

Bickel, Hubert; Pinker, Katja; Polanec, Stephan; Magometschnigg, Heinrich; Wengert, Georg; Spick, Claudio; Bogner, Wolfgang; Bago-Horvath, Zsuzsanna; Helbich, Thomas H; Baltzer, Pascal

2017-05-01

To investigate the influence of region-of-interest (ROI) placement and different apparent diffusion coefficient (ADC) parameters on ADC values, diagnostic performance, reproducibility and measurement time in breast tumours. In this IRB-approved, retrospective study, 149 histopathologically proven breast tumours (109 malignant, 40 benign) in 147 women (mean age 53.2) were investigated. Three radiologists independently measured minimum, mean and maximum ADC, each using three ROI placement approaches:1 - small 2D-ROI, 2 - large 2D-ROI and 3 - 3D-ROI covering the whole lesion. One reader performed all measurements twice. Median ADC values, diagnostic performance, reproducibility, and measurement time were calculated and compared between all combinations of ROI placement approaches and ADC parameters. Median ADC values differed significantly between the ROI placement approaches (p < .001). Minimum ADC showed the best diagnostic performance (AUC .928-.956), followed by mean ADC obtained from 2D ROIs (.926-.94). Minimum and mean ADC showed high intra- (ICC .85-.94) and inter-reader reproducibility (ICC .74-.94). Median measurement time was significantly shorter for the 2D ROIs (p < .001). ROI placement significantly influences ADC values measured in breast tumours. Minimum and mean ADC acquired from 2D-ROIs are useful for the differentiation of benign and malignant breast lesions, and are highly reproducible, with rapid measurement. • Region of interest placement significantly influences apparent diffusion coefficient of breast tumours. • Minimum and mean apparent diffusion coefficient perform best and are reproducible. • 2D regions of interest perform best and provide rapid measurement times.

A low-power inverter-based CMOS level-crossing analog-to-digital converter for low-frequency biosignal sensing

NASA Astrophysics Data System (ADS)

Tanaka, Suiki; Niitsu, Kiichi; Nakazato, Kazuo

2016-03-01

Low-power analog-to-digital conversion is a key technique for power-limited biomedical applications such as power-limited continuous glucose monitoring. However, a conventional uniform-sampling analog-to-digital converter (ADC) is not suitable for nonuniform biosignals. A level-crossing ADC (LC-ADC) is a promising candidate for low-power biosignal processing because of its event-driven properties. The LC-ADC acquires data by level-crossing sampling. When an input signal crosses the threshold level, the LC-ADC samples the signal. The conventional LC-ADC employs a power-hungry comparator. In this paper, we present a low-power inverter-based LC-ADC. By adjusting the threshold level of the inverter, it can be used as a threshold-fixed window comparator. By using the inverter as an alternative to a comparator, power consumption can be markedly reduced. As a result, the total power consumption is successfully reduced by 90% of that of previous LC-ADC. The inverter-based LC-ADC was found to be very suitable for use in power-limited biomedical devices.

A preprocessor for the Urbana coherent-scatter radar

NASA Technical Reports Server (NTRS)

Zendt, F. T.; Bowhill, S. A.

1982-01-01

The design, interfacing, testing, and operation of a preprocessor to increase the altitude and temporal resolution of the present coherent-scatter system are described. This system upgrade requires an increase in the data collection rate. Replacing the present, relatively slow, ADC with two high speed ADCs achieves the increased echo sampling rate desired. To stay within the capabilities of the main computer's I/O and processing rate the data must be reduced before transfer to the main computer. Thus the preprocessor also coherently integrates the data before transfer.

Intravoxel Incoherent Motion–derived Histogram Metrics for Assessment of Response after Combined Chemotherapy and Radiation Therapy in Rectal Cancer: Initial Experience and Comparison between Single-Section and Volumetric Analyses

PubMed Central

Vargas, Hebert Alberto; Lakhman, Yulia; Sudre, Romain; Do, Richard K. G.; Bibeau, Frederic; Azria, David; Assenat, Eric; Molinari, Nicolas; Pierredon, Marie-Ange; Rouanet, Philippe; Guiu, Boris

2016-01-01

Purpose To determine the diagnostic performance of intravoxel incoherent motion (IVIM) parameters and apparent diffusion coefficient (ADC) to assess response to combined chemotherapy and radiation therapy (CRT) in patients with rectal cancer by using histogram analysis derived from whole-tumor volumes and single-section regions of interest (ROIs). Materials and Methods The institutional review board approved this retrospective study of 31 patients with rectal cancer who underwent magnetic resonance (MR) imaging before and after CRT, including diffusion-weighted imaging with 34 b values prior to surgery. Patient consent was not required. ADC, perfusion-related diffusion fraction (f), slow diffusion coefficient (D), and fast diffusion coefficient (D*) were calculated on MR images acquired before and after CRT by using biexponential fitting. ADC and IVIM histogram metrics and median values were obtained by using whole-tumor volume and single-section ROI analyses. All ADC and IVIM parameters obtained before and after CRT were compared with histopathologic findings by using t tests with Holm-Sidak correction. Receiver operating characteristic curves were generated to evaluate the diagnostic performance of IVIM parameters derived from whole-tumor volume and single-section ROIs for prediction of histopathologic response. Results Extreme values aside, results of histogram analysis of ADC and IVIM were equivalent to median values for tumor response assessment (P > .06). Prior to CRT, none of the median ADC and IVIM diffusion metrics correlated with subsequent tumor response (P > .36). Median D and ADC values derived from either whole-volume or single-section analysis increased significantly after CRT (P ≤ .01) and were significantly higher in good versus poor responders (P ≤ .02). Median IVIM f and D* values did not significantly change after CRT and were not associated with tumor response to CRT (P > .36). Interobserver agreement was excellent for whole-tumor volume analysis (range, 0.91–0.95) but was only moderate for single-section ROI analysis (range, 0.50–0.63). Conclusion Median D and ADC values obtained after CRT were useful for discrimination between good and poor responders. Histogram metrics did not add to the median values for assessment of tumor response. Volumetric analysis demonstrated better interobserver reproducibility when compared with single-section ROI analysis. © RSNA, 2016 Online supplemental material is available for this article. PMID:26919562

Value of Diffusion-Weighted Magnetic Resonance Imaging for Prediction and Early Assessment of Response to Neoadjuvant Radiochemotherapy in Rectal Cancer: Preliminary Results

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

Lambrecht, Maarten, E-mail: maarten.lambrecht@uzleuven.be; Vandecaveye, Vincent; De Keyzer, Frederik

2012-02-01

Purpose: To evaluate diffusion-weighted magnetic resonance imaging (DWI) for response prediction before and response assessment during and early after preoperative radiochemotherapy (RCT) for locally advanced rectal cancer (LARC). Methods and Materials: Twenty patients receiving RCT for LARC underwent MRI including DWI before RCT, after 10-15 fractions and 1 to 2 weeks before surgery. Tumor volume and apparent diffusion coefficient (ADC; b-values: 0-1000 s/mm{sup 2}) were determined at all time points. Pretreatment tumor ADC and volume, tumor ADC change ( Increment ADC), and volume change ( Increment V) between pretreatment and follow-up examinations were compared with histopathologic findings after total mesorectalmore » excision (pathologic complete response [pCR] vs. no pCR, ypT0-2 vs. ypT3-4, T-downstaging or not). The discriminatory capability of pretreatment tumor ADC and volume, Increment ADC, and Increment V for the detection of pCR was compared with receiver operating characteristics analysis. Results: Pretreatment ADC was significantly lower in patients with pCR compared with patients without (in mm{sup 2}/s: 0.94 {+-} 0.12 Multiplication-Sign 10{sup -3} vs. 1.19 {+-} 0.22 Multiplication-Sign 10{sup -3}, p = 0.003), yielding a sensitivity of 100% and specificity of 86% for detection of pCR. The volume reduction during and after RCT was significantly higher in patients with pCR compared with patients without (in %: {Delta}V{sub during}: -62 {+-} 16 vs. -33 {+-} 16, respectively, p = 0.015; and {Delta}V{sub post}: -86 {+-} 12 vs. -60 {+-} 21, p = 0.012), yielding a sensitivity of 83% and specificity of 71% for the {Delta}V{sub during} and, respectively, 83% and 86% for the {Delta}V{sub post}. The Increment ADC during ({Delta}ADC{sub during}) and after RCT ({Delta}ADC{sub post}) showed a significantly higher value in patients with pCR compared with patients without (in %: {Delta}ADC{sub during}: 72 {+-} 14 vs. 16 {+-} 12, p = 0.0006; and {Delta}ADC{sub post}: 88 {+-} 35 vs. 26 {+-} 19, p = 0.0011), yielding a sensitivity and specificity of 100% for the {Delta}ADC{sub during} and, respectively, 100% and 93% for the {Delta}ADC{sub post}. Conclusions: These initial findings indicate that DWI, using pretreatment ADC, {Delta}ADC{sub during}, and {Delta}ADC{sub post} may be useful for prediction and early assessment of pathologic response to preoperative RCT of LARC, with higher accuracy than volumetric measurements.« less

Development and Properties of Valine-Alanine based Antibody-Drug Conjugates with Monomethyl Auristatin E as the Potent Payload

PubMed Central

Fan, Shiyong; Zhong, Wu; Zhou, Xinbo; Li, Song

2017-01-01

Antibody-drug conjugates (ADCs), designed to selectively deliver cytotoxic agents to antigen-bearing cells, are poised to become an important class of cancer therapeutics. Human epithelial growth factor receptor (HER2) is considered an effective target for cancer treatment, and a HER2-targeting ADC has shown promising results. Most ADCs undergoing clinical evaluation contain linkers that have a lysosomal protease-cleavable dipeptide, of which the most common is valine-citrulline (VC). However, valine-alanine (VA), another dipeptide comprising two human essential amino acids, has been used in next generation ADCs loading new toxins, but the druggable properties of ADCs loaded the most popular monomethyl auristatin E (MMAE) remain to be further explored. In this study, we generated VA-based ADCs that connected MMAE to an anti-HER2 antibody. We studied the differences in the preparation process, in vitro stability, cathepsin B activity and in vitro cytotoxicity of VA-based ADC compared to the ADC of VC. VA had comparable performance to VC, which preliminarily displays its practicability. Additional efficacy and safety studies in a xenograft model indicate this novel ADC exerted potent anti-tumor activity and negligible toxicity. The results of this study show the application potential of VA-based ADC with MMAE as the payload. PMID:28841157

Development and Properties of Valine-Alanine based Antibody-Drug Conjugates with Monomethyl Auristatin E as the Potent Payload.

PubMed

Wang, Yanming; Fan, Shiyong; Zhong, Wu; Zhou, Xinbo; Li, Song

2017-08-25

Antibody-drug conjugates (ADCs), designed to selectively deliver cytotoxic agents to antigen-bearing cells, are poised to become an important class of cancer therapeutics. Human epithelial growth factor receptor (HER2) is considered an effective target for cancer treatment, and a HER2-targeting ADC has shown promising results. Most ADCs undergoing clinical evaluation contain linkers that have a lysosomal protease-cleavable dipeptide, of which the most common is valine-citrulline (VC). However, valine-alanine (VA), another dipeptide comprising two human essential amino acids, has been used in next generation ADCs loading new toxins, but the druggable properties of ADCs loaded the most popular monomethyl auristatin E (MMAE) remain to be further explored. In this study, we generated VA-based ADCs that connected MMAE to an anti-HER2 antibody. We studied the differences in the preparation process, in vitro stability, cathepsin B activity and in vitro cytotoxicity of VA-based ADC compared to the ADC of VC. VA had comparable performance to VC, which preliminarily displays its practicability. Additional efficacy and safety studies in a xenograft model indicate this novel ADC exerted potent anti-tumor activity and negligible toxicity. The results of this study show the application potential of VA-based ADC with MMAE as the payload.

Seroprevalence of Neutralizing Antibodies against Human Adenovirus Type-5 and Chimpanzee Adenovirus Type-68 in Cancer Patients

PubMed Central

Zhao, Hua; Xu, Can; Luo, Xiaoli; Wei, Feng; Wang, Ning; Shi, Huiying; Ren, Xiubao

2018-01-01

Since the preclinical results about chimpanzee adenovirus serotype-68 (AdC68)-based vaccine showed an encouraging results, it reminded us that AdC68 may be a suitable cancer vaccine vector. Previous study indicated that the seroprevalence of neutralizing antibodies (NAbs) against adenovirus was different between cancer patients and healthy volunteers. Knowledge regarding the prevalence rates of AdC68 NAbs for cancer patients is lacking. Therefore, assessing the preexistence of NAbs against AdC68 in cancer patients could provide useful insights for developing future AdC68-based cancer vaccines. In this study, 440 patients with different pathological types of tumors and 204 healthy adult volunteers were enrolled to evaluate the NAbs against AdC68 and human adenovirus serotype-5 (AdHu5). The seroprevalence of NAbs against AdC68 was much lower than that against AdHu5 in cancer subjects (43.64 vs. 67.05%, P < 0.01). The seroprevalence rates of NAbs to AdC68 in the cancer subjects were statistically higher than those detected in the healthy adult volunteers (43.64 vs. 23.53%, P = 0.000). The seroprevalence rates of AdC68 NAbs were much lower in lung, laryngeal, esophageal, and cervical cancer patients compared with oropharyngeal, colon, and rectal cancer patients. Furthermore, the seroprevalence rates of AdC68 NAbs were much lower in lung adenocarcinoma patients than in lung squamous cell carcinoma patients (35.00 vs. 70.00%, P < 0.05). No significant difference in the AdC68 NAbs among patients with different clinical stages of cancer was detected. The percentage of NAbs against AdC68 was significantly lower than that against AdHu5 (P < 0.05) in stage-I, -II, and -III cancer patients. No significant difference between the percentage of NAbs against AdC68 and AdHu5 in the subjects with stage-IV cancer was detected. The study also demonstrated the distribution of AdHu5 and AdC68 NAb titers for the positive samples. It showed that very low NAb titers against AdC68 with respect to AdHu5 in both healthy subjects and cancer subjects, especially in lung, laryngeal, esophageal, gastric, and cervical carcinomas. Also, the titer of NAbs against AdC68 was significantly lower than that against AdHu5 in the same clinical stage and age group (P < 0.05). Taken together, the present study showed that NAbs against AdC68 is much lower than AdHu5, especially in lung adenocarcinoma, laryngeal cancer, esophageal cancer, and cervical cancer patients. These results provided strong support for candidating AdC68 as a suitable vector of cancer vaccines. PMID:29563911

Improved Lysosomal Trafficking Can Modulate the Potency of Antibody Drug Conjugates.

PubMed

DeVay, Rachel M; Delaria, Kathy; Zhu, Guoyun; Holz, Charles; Foletti, Davide; Sutton, Janette; Bolton, Gary; Dushin, Russell; Bee, Christine; Pons, Jaume; Rajpal, Arvind; Liang, Hong; Shelton, David; Liu, Shu-Hui; Strop, Pavel

2017-04-19

Antibody drug conjugates (ADCs) provide an efficacious and relatively safe means by which chemotherapeutic agents can be specifically targeted to cancer cells. In addition to the selection of antibody targets, ADCs offer a modular design that allows selection of ADC characteristics through the choice of linker chemistries, toxins, and conjugation sites. Many studies have indicated that release of toxins bound to antibodies via noncleavable linker chemistries relies on the internalization and intracellular trafficking of the ADC. While this can make noncleavable ADCs more stable in the serum, it can also result in lower efficacy when their respective targets are not internalized efficiently or are recycled back to the cell surface following internalization. Here, we show that a lysosomally targeted ADC against the protein APLP2 mediates cell killing, both in vitro and in vivo, more effectively than an ADC against Trop2, a protein with less efficient lysosomal targeting. We also engineered a bispecific ADC with one arm targeting HER2 for the purpose of directing the ADC to tumors, and the other arm targeting APLP2, whose purpose is to direct the ADC to lysosomes for toxin release. This proof-of-concept bispecific ADC demonstrates that this technology can be used to shift the intracellular trafficking of a constitutively recycled target by directing one arm of the antibody against a lysosomally delivered protein. Our data also show limitations of this approach and potential future directions for development.

A sub-microwatt asynchronous level-crossing ADC for biomedical applications.

PubMed

Li, Yongjia; Zhao, Duan; Serdijn, Wouter A

2013-04-01

A continuous-time level-crossing analog-to-digital converter (LC-ADC) for biomedical applications is presented. When compared to uniform-sampling (US) ADCs LC-ADCs generate fewer samples for various sparse biomedical signals. Lower power consumption and reduced design complexity with respect to conventional LC-ADCs are achieved due to: 1) replacing the n-bit digital-to-analog converter (DAC) with a 1-bit DAC; 2) splitting the level-crossing detections; and 3) fixing the comparison window. Designed and implemented in 0.18 μm CMOS technology, the proposed ADC uses a chip area of 220 × 203 μm(2). Operating from a supply voltage of 0.8 V, the ADC consumes 313-582 nW from 5 Hz to 5 kHz and achieves an ENOB up to 7.9 bits.

Volumetric segmentation of ADC maps and utility of standard deviation as measure of tumor heterogeneity in soft tissue tumors.

PubMed

Singer, Adam D; Pattany, Pradip M; Fayad, Laura M; Tresley, Jonathan; Subhawong, Ty K

2016-01-01

Determine interobserver concordance of semiautomated three-dimensional volumetric and two-dimensional manual measurements of apparent diffusion coefficient (ADC) values in soft tissue masses (STMs) and explore standard deviation (SD) as a measure of tumor ADC heterogeneity. Concordance correlation coefficients for mean ADC increased with more extensive sampling. Agreement on the SD of tumor ADC values was better for large regions of interest and multislice methods. Correlation between mean and SD ADC was low, suggesting that these parameters are relatively independent. Mean ADC of STMs can be determined by volumetric quantification with high interobserver agreement. STM heterogeneity merits further investigation as a potential imaging biomarker that complements other functional magnetic resonance imaging parameters. Copyright © 2016 Elsevier Inc. All rights reserved.

Time Trends in Epidemiologic Characteristics and Imaging Features of Lung Adenocarcinoma: A Population Study of 21,113 Cases in China

PubMed Central

Zhang, Li; Li, Meng; Wu, Ning; Chen, Yuheng

2015-01-01

Objectives This study aims to describe time trends of epidemiologic characteristics and imaging features over 14 years among histologically confirmed lung adenocarcinoma (ADC) in China and to discuss the possible reasons for these changes. Materials and Methods Data of 21,113 pathologically confirmed lung cancer patients from January 1999 to December 2012 were analyzed retrospectively. Preoperative high-resolution computer tomography (HRCT) images were available and reviewed in 5,439 lung ADC patients since 2005. Time trends of the ADC proportion of lung cancer cases, gender distribution, age at diagnosis, the proportion of early-stage ADC and imaging features were investigated. Results The proportion of ADC increased during the 14 years (P = 0.000). The ratio of female to male ADC cases was higher than both squamous cell carcinoma (SQCC) and total lung cancer cases (P = 0.000). The median age at diagnosis of ADC patients was younger than that of both SQCC and total lung cancer during the 14 years (P = 0.000). The proportion of age group 45–59 years increased in total lung cancer cases (P = 0.000). When stratified by lung cancer histopathologic subtypes, this trend was also observed in ADC (P = 0.001) and SQCC (P = 0.007). The proportion of early-stage cases of ADC increased from 2008 to 2012 (P < 0.001). The proportion of subsolid nodules (SSN) in ADC increased (P = 0.001) from 2005 to 2012. Conclusion The data suggests that the proportion of ADC increased from 1999 to 2012 especially in middle-aged, female patients; early-stage ADC and SSN on HRCT images gradually increased, which may have been caused by a change in smoking habits and increased application of HRCT. PMID:26317971

Capacitor-Chain Successive-Approximation ADC

NASA Technical Reports Server (NTRS)

Cunningham, Thomas

2003-01-01

A proposed successive-approximation analog-to-digital converter (ADC) would contain a capacitively terminated chain of identical capacitor cells. Like a conventional successive-approximation ADC containing a bank of binary-scaled capacitors, the proposed ADC would store an input voltage on a sample-and-hold capacitor and would digitize the stored input voltage by finding the closest match between this voltage and a capacitively generated sum of binary fractions of a reference voltage (Vref). However, the proposed capacitor-chain ADC would offer two major advantages over a conventional binary-scaled-capacitor ADC: (1) In a conventional ADC that digitizes to n bits, the largest capacitor (representing the most significant bit) must have 2(exp n-1) times as much capacitance, and hence, approximately 2(exp n-1) times as much area as does the smallest capacitor (representing the least significant bit), so that the total capacitor area must be 2(exp n) times that of the smallest capacitor. In the proposed capacitor-chain ADC, there would be three capacitors per cell, each approximately equal to the smallest capacitor in the conventional ADC, and there would be one cell per bit. Therefore, the total capacitor area would be only about 3(exp n) times that of the smallest capacitor. The net result would be that the proposed ADC could be considerably smaller than the conventional ADC. (2) Because of edge effects, parasitic capacitances, and manufacturing tolerances, it is difficult to make capacitor banks in which the values of capacitance are scaled by powers of 2 to the required precision. In contrast, because all the capacitors in the proposed ADC would be identical, the problem of precise binary scaling would not arise.

Apparent Diffusion Coefficient (ADC) value: a potential imaging biomarker that reflects the biological features of rectal cancer.

PubMed

Sun, Yiqun; Tong, Tong; Cai, Sanjun; Bi, Rui; Xin, Chao; Gu, Yajia

2014-01-01

We elected to analyze the correlation between the pre-treatment apparent diffusion coefficient (ADC) and the clinical, histological, and immunohistochemical status of rectal cancers. Forty-nine rectal cancer patients who received surgical resection without neoadjuvant therapy were selected that underwent primary MRI and diffusion-weighted imaging (DWI). Tumor ADC values were determined and analyzed to identify any correlations between these values and pre-treatment CEA or CA19-9 levels, and/or the histological and immunohistochemical properties of the tumor. Inter-observer agreement of confidence levels from two separate observers was suitable for ADC measurement (k  =  0.775). The pre-treatment ADC values of different T stage tumors were not equal (p  =  0.003). The overall trend was that higher T stage values correlated with lower ADC values. ADC values were also significantly lower for the following conditions: tumors with the presence of extranodal tumor deposits (p  =  0.006) and tumors with CA19-9 levels ≥ 35 g/ml (p  =  0.006). There was a negative correlation between Ki-67 LI and the ADC value (r  =  -0.318, p  =  0.026) and between the AgNOR count and the ADC value (r  =  -0.310, p  =  0.030). Significant correlations were found between the pre-treatment ADC values and T stage, extranodal tumor deposits, CA19-9 levels, Ki-67 LI, and AgNOR counts in our study. Lower ADC values were associated with more aggressive tumor behavior. Therefore, the ADC value may represent a useful biomarker for assessing the biological features and possible relationship to the status of identified rectal cancers.

Differentiation of Benign and Malignant Head and Neck Lesions With Diffusion Tensor Imaging and DWI.

PubMed

Koontz, Nicholas A; Wiggins, Richard H

2017-05-01

The purpose of this study was to determine whether diffusion tensor imaging (DTI) can be used to differentiate between benign and malignant head and neck lesions. This retrospective study included patients with head and neck lesions who underwent clinical MRI at 1.5 or 3 T with DWI or DTI parameters. ROI analysis was performed, with lesion-to-medulla apparent diffusion coefficient (ADC) ratios generated. Sixty-five patients with head and neck lesions were included (71 benign, 40 malignant). Twenty-one patients had multiple lesions. Statistically significant differences (p < 0.001) were seen in the mean ADC values ± SD of malignant and benign lesions (0.55 × 10 -3 ± 0.14 × 10 -3 mm 2 /s vs 0.89 × 10 -3 ± 0.29 × 10 -3 mm 2 /s, respectively) and in the mean ADC ratios of malignant and benign lesions (0.88 ± 0.21 vs 1.40 ± 0.44, respectively) with DTI parameters. DTI and DWI parameters produced similar mean ADC ratio values for malignant (0.88 ± 0.21 and 0.92 ± 0.54, respectively) and benign lesions (1.40 ± 0.44 and 1.79 ± 0.52, respectively). ADC ratio thresholds for predicting malignancy for DTI (ADC ratio ≤ 1) and DWI (ADC ratio ≤ 0.94) were also similar. DTI is a useful predictor of malignancy for head and neck lesions, with ADC values of malignant lesions significantly lower than those of benign lesions. DTI ADC values were lower than DWI ADC values for all head and neck lesions in our study group, often below reported malignant DWI threshold values. Normalization of ADC values to an internal control resulted in similar ADC ratios on DWI and DTI.

Utility of Diffusion Weighted Magnetic Resonance Imaging with Multiple B Values in Evaluation of Pancreatic Malignant and Benign Lesions and Pancreatitis.

PubMed

Karadeli, Elif; Erbay, Gurcan; Parlakgumus, Alper; Koc, Zafer

2018-02-01

To determine the feasibility of diffusion-weighted imaging in evaluation of pancreatic lesions and in differentiation of benign from malignant lesions. Descriptive study. Baskent University Adana Teaching and Research Center, Adana, Turkey, between September 2013 and May 2015. Forty-three lesions [pancreas adenocarcinoma (n=25)], pancreatitis (n=10), benign lesion (n=8)] were utilized with diffusion-weighted magnetic resonance imaging with multiple b-values. Different ADC maps of diffusion weighted images by using b-values were acquired. The median ADC at all b values for malignant lesions was significantly different from that for benign lesions (p<0.001). When ADCs at all b values were compared between benign lesions/normal parenchyma and malignant lesions/normal parenchyma, there was a significant statistical difference in all b values between benign and malignant lesions except at b 50 and b 200 (p<0.05). The lesion/normal parenchyma ADC ratio for b 600 value (AUC=0.804) was more effective than the lesion ADC for b 600 value (AUC=0.766) in differentiation of benign and malignant lesions. The specificity and sensitivity of the lesion/normal parenchyma ADC ratio were higher than those of ADC values of lesions. When the ADC was compared between benign lesions and pancreatitis, a significant difference was found at all b values (p<0.001). There was not a statistically significant difference between the ADC for pancreatitis and that for malignant lesions at any b value combinations (p>0.05). Diffusion-weighted magnetic resonance images can be helpful in differentiation of pancreatic carcinoma and benign lesions. Lesion ADC / normal parenchyma ADC ratios are more important than lesion ADC values in assessment of pancreatic lesions.

Beam Instrument Development System

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

DOOLITTLE, LAWRENCE; HUANG, GANG; DU, QIANG

Beam Instrumentation Development System (BIDS) is a collection of common support libraries and modules developed during a series of Low-Level Radio Frequency (LLRF) control and timing/synchronization projects. BIDS includes a collection of Hardware Description Language (HDL) libraries and software libraries. The BIDS can be used for the development of any FPGA-based system, such as LLRF controllers. HDL code in this library is generic and supports common Digital Signal Processing (DSP) functions, FPGA-specific drivers (high-speed serial link wrappers, clock generation, etc.), ADC/DAC drivers, Ethernet MAC implementation, etc.

Role of exponential apparent diffusion coefficient in characterizing breast lesions by 3.0 Tesla diffusion-weighted magnetic resonance imaging

PubMed Central

Kothari, Shweta; Singh, Archana; Das, Utpalendu; Sarkar, Diptendra K; Datta, Chhanda; Hazra, Avijit

2017-01-01

Objective: To evaluate the role of exponential apparent diffusion coefficient (ADC) as a tool for differentiating benign and malignant breast lesions. Patients and Methods: This prospective observational study included 88 breast lesions in 77 patients (between 18 and 85 years of age) who underwent 3T breast magnetic resonance imaging (MRI) including diffusion-weighted imaging (DWI) using b-values of 0 and 800 s/mm2 before biopsy. Mean exponential ADC and ADC of benign and malignant lesions obtained from DWI were compared. Receiver operating characteristics (ROC) curve analysis was undertaken to identify any cut-off for exponential ADC and ADC to predict malignancy. P value of <0.05 was considered statistically significant. Histopathology was taken as the gold standard. Results: According to histopathology, 65 lesions were malignant and 23 were benign. The mean ADC and exponential ADC values of malignant lesions were 0.9526 ± 0.203 × 10−3 mm2/s and 0.4774 ± 0.071, respectively, and for benign lesions were 1.48 ± 0.4903 × 10−3 mm2/s and 0.317 ± 0.1152, respectively. For both the parameters, differences were highly significant (P < 0.001). Cut-off value of ≤0.0011 mm2/s (P < 0.0001) for ADC provided 92.3% sensitivity and 73.9% specificity, whereas with an exponential ADC cut-off value of >0.4 (P < 0.0001) for malignant lesions, 93.9% sensitivity and 82.6% specificity was obtained. The performance of ADC and exponential ADC in distinguishing benign and malignant breast lesions based on respective cut-offs was comparable (P = 0.109). Conclusion: Exponential ADC can be used as a quantitative adjunct tool for characterizing breast lesions with comparable sensitivity and specificity as that of ADC. PMID:28744085

ADC Histogram Analysis of Cervical Cancer Aids Detecting Lymphatic Metastases-a Preliminary Study.

PubMed

Schob, Stefan; Meyer, Hans Jonas; Pazaitis, Nikolaos; Schramm, Dominik; Bremicker, Kristina; Exner, Marc; Höhn, Anne Kathrin; Garnov, Nikita; Surov, Alexey

2017-12-01

Apparent diffusion coefficient (ADC) histogram analysis has been used to some extent in cervical cancer (CC) to distinguish between low-grade and high-grade tumors. Although this differentiation is undoubtedly helpful, it would be even more crucial in the presurgical setting to determine whether a tumor already gained the potential to metastasize via the lymphatic system. So far, no studies investigated the potential of 3T ADC histogram analysis in CC to differentiate between nodal-positive and nodal-negative entities. Therefore, the principal aim of our study was to investigate the potential of 3T ADC histogram analysis to differentiate between CC with and without lymph node metastasis. The second aim was to elucidate possible differences in ADC histogram parameters between CC with limited vs. advanced tumor stages and well-differentiated vs. undifferentiated lesions. Finally, correlations of p53 expression and Ki-67 index with ADC parameters were analyzed. Eighteen female patients (mean age 55.4 years, range 32-79 years) with histopathologically confirmed cervical squamous cell carcinoma of the uterine cervix were prospectively enrolled. Tumor stages, tumor grading, status of metastatic dissemination, Ki67-index, and p53 expression were assessed in these patients. Diffusion weighted imaging (DWI) was obtained in a 3T scanner using the following b values: b0 and b1000 s/mm 2 . Group comparisons using Mann-Whitney U test revealed the following findings: nodal-positive CC had statistically significant lower ADC parameters (ADCmin, ADCmean, median ADC, Mode, p10, p25, p75, and p90) in comparison to nodal-negative CC (all p < 0.05). ADCentropy was significantly elevated (p = 0.046) in tumors with advanced T stages (T3/4) compared to tumors with limited T stage (T2). ADCmin values were different in a statistically significant manner comparing G1/G2 and G3 tumors (40.45 ± 18.63 vs. 65.0 ± 23.63 × 10-5 mm2 s -1 , p = 0.035). Furthermore, Spearman Rho calculation identified an inverse correlation between ADCentropy and p53 expression (r = -0.472, p = 0.048). The main finding of our study is the discriminability of nodal-positive from nodal-negative CC using ADC histogram analysis in 3T DWI. This information is crucial for the gynecological surgeon to identify the optimal treatment strategy for patients suffering from CC. Furthermore, ADCentropy was identified as a potential imaging biomarker for tumor heterogeneity and might be able to indicate further molecular changes like loss of p53 expression, which is associated with EMT and consequentially indicates a poor prognosis in CC. Finally, our study confirmed the findings of previous works, which indicated that histogram analysis of ADC maps can distinguish between low-grade and high-grade CC. In conclusion, it can be stated that ADC histogram analysis provides additional, prognostically important information on tumor biology in CC.

Superconducting Digital Multiplexers for Sensor Arrays

NASA Technical Reports Server (NTRS)

Kadin, Alan M.; Brock, Darren K.; Gupta, Deepnarayan

2004-01-01

Arrays of cryogenic microbolometers and other cryogenic detectors are being developed for infrared imaging. If the signal from each sensor is amplified, multiplexed, and digitized using superconducting electronics, then this data can be efficiently read out to ambient temperature with a minimum of noise and thermal load. HYPRES is developing an integrated system based on SQUID amplifiers, a high-resolution analog-to-digital converter (ADC) based on RSFQ (rapid single flux quantum) logic, and a clocked RSFQ multiplexer. The ADC and SQUIDs have already been demonstrated for other projects, so this paper will focus on new results of a digital multiplexer. Several test circuits have been fabricated using Nb Josephson technology and are about to be tested at T = 4.2 K, with a more complete prototype in preparation.

Diffusion-weighted magnetic resonance imaging of femoral head osteonecrosis in two groups of patients: Legg-Perthes-Calve and Avascular necrosis.

PubMed

Ozel, Betul Duran; Ozel, Deniz; Ozkan, Fuat; Halefoglu, Ahmet M

2016-03-01

The aim of this prospective study was to evaluate the value of diffusion-weighted magnetic resonance imaging (DW-MRI) in patients with osteonecrosis. Patients were divided into two subgroups as avascular necrosis (AVN) of femoral head for adult group and Legg-Calvé-Perthes (LCP) patients for children. Seventeen patients with femoral head AVN (mean age 42.3 years) and 17 patients with LCP (mean age 8.2 years) were included in this study. Diagnosis confirmed with clinical and other imaging procedures among the patients complaining hip pain. DW images were obtained using the single-shot echo planar sequence and had b values of 0, 500, 1000 s/mm(2). The apparent diffusion coefficient (ADC) values were measured from ADC maps in epiphysis of patients with AVN, both from metaphysis and epiphysis in patients with LCP, respectively. Mann-Whitney U test was used to compare ADC values. The mean ADC value of femoral heads (1.285 ± 0.204 × 10(-3) mm(2)/s) was increased in patients with AVN when compared to normal bone tissue (0.209 ± 0.214 × 10(-3) mm(2)/s) (p < 0.01). The mean ADC values (×10(-3) mm(2)/s) of both metaphysis (0.852 ± 0.293) and epiphysis (0.843 ± 0.332) were also increased in patients with LCP and differences were statistically significant (p < 0.01). As a result, osteonecrosis shows increased ADC values. But it is a controversial concept that DWI offers a valuable data to conventional MRI or not. However, as there are report states, there is a correlation between the stage of the disease with ADC values in the LCP disease. DWI is a fast, without-contrast administration technique and provides quantitative values additional to conventional MR techniques; we believe DWI may play an additional assistance to the diagnosis and treatment for LCP patients. Multicentric larger group studies may provide additional data to this issue.

Effect of gadolinium injection on diffusion-weighted imaging with background body signal suppression (DWIBS) imaging of breast lesions.

PubMed

Moschetta, Marco; Telegrafo, Michele; Rella, Leonarda; Stabile Ianora, Amato Antonio; Angelelli, Giuseppe

2014-12-01

Diffusion-weighted imaging with background body signal suppression (DWIBS) provides both qualitative and quantitative imaging of breast lesions and are usually performed before contrast material injection (CMI). This study aims to assess whether the administration of gadolinium significantly affects DWIBS imaging. 200 patients were prospectively evaluated by MRI with STIR, TSE-T2, pre-CMI DWIBS, contrast enhanced THRIVE-T1 and post-CMI DWIBS sequences. Pre and post-CMI DWIBS were analyzed searching for the presence of breast lesions and calculating the ADC value. ADC values of ≤1.44×10(-3) mm(2)/s were considered suspicious for malignancy. This analysis was then compared with the histological findings. Sensitivity, specificity, diagnostic accuracy (DA), positive predictive value (PPV) and negative (NPV) were calculated for both sequences and represented by ROC analysis. Pre and post-CMI ADC values were compared by using the paired t test. In 150/200 (59%) patients, pre and post-CMI DWIBS indicated the presence of breast lesions, 53 (35%) with ADC values of >1.44×10(-3) mm(2)/s and 97 (65%) with ADC≤1.44×10(-3) mm(2)/s. Pre-CMI and post-DWIBS sequences obtained the same sensitivity, specificity, DA, PPV and NPV values of 97%, 83%, 89%, 79% and 98%. The mean ADC value of benign lesions was 1.831±0.18×10(-3) mm(2)/s before and 1.828±0.18×10(-3) mm(2)/s after CMI. The mean ADC value of the malignant lesions was 1.146±0.16×10(-3) mm(2)/s before and 1.144±0.16×10(-3) mm(2)/s after CMI. No significant difference was found between pre and post CMI ADC values (p>0.05). DWIBS imaging is not influenced by CMI. Breast MR protocol could be modified by placing DWIBS after dynamic contrast enhanced sequences in order to maximize patient cooperation. Copyright © 2014 Elsevier Inc. All rights reserved.

Pretreatment ADC histogram analysis is a predictive imaging biomarker for bevacizumab treatment but not chemotherapy in recurrent glioblastoma.

PubMed

Ellingson, B M; Sahebjam, S; Kim, H J; Pope, W B; Harris, R J; Woodworth, D C; Lai, A; Nghiemphu, P L; Mason, W P; Cloughesy, T F

2014-04-01

Pre-treatment ADC characteristics have been shown to predict response to bevacizumab in recurrent glioblastoma multiforme. However, no studies have examined whether ADC characteristics are specific to this particular treatment. The purpose of the current study was to determine whether ADC histogram analysis is a bevacizumab-specific or treatment-independent biomarker of treatment response in recurrent glioblastoma multiforme. Eighty-nine bevacizumab-treated and 43 chemotherapy-treated recurrent glioblastoma multiformes never exposed to bevacizumab were included in this study. In all patients, ADC values in contrast-enhancing ROIs from MR imaging examinations performed at the time of recurrence, immediately before commencement of treatment for recurrence, were extracted and the resulting histogram was fitted to a mixed model with a double Gaussian distribution. Mean ADC in the lower Gaussian curve was used as the primary biomarker of interest. The Cox proportional hazards model and log-rank tests were used for survival analysis. Cox multivariate regression analysis accounting for the interaction between bevacizumab- and non-bevacizumab-treated patients suggested that the ability of the lower Gaussian curve to predict survival is dependent on treatment (progression-free survival, P = .045; overall survival, P = .003). Patients with bevacizumab-treated recurrent glioblastoma multiforme with a pretreatment lower Gaussian curve > 1.2 μm(2)/ms had a significantly longer progression-free survival and overall survival compared with bevacizumab-treated patients with a lower Gaussian curve < 1.2 μm(2)/ms. No differences in progression-free survival or overall survival were observed in the chemotherapy-treated cohort. Bevacizumab-treated patients with a mean lower Gaussian curve > 1.2 μm(2)/ms had a significantly longer progression-free survival and overall survival compared with chemotherapy-treated patients. The mean lower Gaussian curve from ADC histogram analysis is a predictive imaging biomarker for bevacizumab-treated, not chemotherapy-treated, recurrent glioblastoma multiforme. Patients with recurrent glioblastoma multiforme with a mean lower Gaussian curve > 1.2 μm(2)/ms have a survival advantage when treated with bevacizumab.

Endometrial Cancer: Combined MR Volumetry and Diffusion-weighted Imaging for Assessment of Myometrial and Lymphovascular Invasion and Tumor Grade

PubMed Central

Reinhold, Caroline; Alsharif, Shaza S.; Addley, Helen; Arceneau, Jocelyne; Molinari, Nicolas; Guiu, Boris; Sala, Evis

2015-01-01

Purpose To investigate magnetic resonance (MR) volumetry of endometrial tumors and its association with deep myometrial invasion, tumor grade, and lymphovascular invasion and to assess the value of apparent diffusion coefficient (ADC) histographic analysis of the whole tumor volume for prediction of tumor grade and lymphovascular invasion. Materials and Methods The institutional review board approved this retrospective study; patient consent was not required. Between May 2010 and May 2012, 70 women (mean age, 64 years; range, 24–91 years) with endometrial cancer underwent preoperative MR imaging, including axial oblique and sagittal T2-weighted, dynamic contrast material–enhanced, and diffusion-weighted imaging. Volumetry of the tumor and uterus was performed during the six sequences, with manual tracing of each section, and the tumor volume ratio (TVR) was calculated. ADC histograms were generated from pixel ADCs from the whole tumor volume. The threshold of TVR associated with myometrial invasion was assessed by using receiver operating characteristic curves. An independent sample Mann Whitney U test was used to compare differences in ADCs, skewness, and kurtosis between tumor grade and the presence of lymphovascular invasion. Results No significant difference in tumor volume and TVR was found among the six MR imaging sequences (P = .95 and .86, respectively). A TVR greater than or equal to 25% allowed prediction of deep myometrial invasion with sensitivity of 100% and specificity of 93% (area under the curve, 0.96; 95% confidence interval: 0.86, 0.99) at axial oblique diffusion-weighted imaging. A TVR of greater than or equal to 25% was associated with grade 3 tumors (P = .0007) and with lymphovascular invasion (P < .0001). There was no significant difference in the ADCs between grades 1 and 2 tumors (P > .05). The minimum, 10th, 25th, 50th, 75th, and 90th percentile ADCs were significantly lower in grade 3 tumors than in grades 1 and 2 tumors (P < .02). Conclusion The combination of whole tumor volume and ADC can be used for prediction of tumor grade, lymphovascular invasion, and depth of myometrial invasion. © RSNA, 2015 PMID:25928157

Can diffusion-weighted imaging serve as a biomarker of fibrosis in pancreatic adenocarcinoma?

PubMed

Hecht, Elizabeth M; Liu, Michael Z; Prince, Martin R; Jambawalikar, Sachin; Remotti, Helen E; Weisberg, Stuart W; Garmon, Donald; Lopez-Pintado, Sara; Woo, Yanghee; Kluger, Michael D; Chabot, John A

2017-08-01

To assess the relationship between diffusion-weighted imaging (DWI) and intravoxel incoherent motion (IVIM)-derived quantitative parameters (apparent diffusion coefficient [ADC], perfusion fraction [f], D slow , diffusion coefficient [D], and D fast , pseudodiffusion coefficient [D*]) and histopathology in pancreatic adenocarcinoma (PAC). Subjects with suspected surgically resectable PAC were prospectively enrolled in this Health Insurance Portability and Accountability Act (HIPAA)-compliant, Institutional Review Board-approved study. Imaging was performed at 1.5T with a respiratory-triggered echo planar DWI sequence using 10 b values. Two readers drew regions of interest (ROIs) over the tumor and adjacent nontumoral tissue. Monoexponential and biexponential fits were used to derive ADC 2b , ADC all , f, D, and D*, which were compared to quantitative histopathology of fibrosis, mean vascular density, and cellularity. Two biexponential IVIM models were investigated and compared: 1) nonlinear least-square fitting based on the Levenberg-Marquardt algorithm, and 2) linear fit using a fixed D* (20 mm 2 /s). Statistical analysis included Student's t-test, Pearson correlation (P < 0.05 was considered significant), intraclass correlation, and coefficients of variance. Twenty subjects with PAC were included in the final cohort. Negative correlation between D and fibrosis (Reader 2: r = -0.57 P = 0.01; pooled P = -0.46, P = 0.04) was observed with a trend toward positive correlation between f and fibrosis (r = 0.44, P = 0.05). ADC 2b was significantly lower in PAC with dense fibrosis than with loose fibrosis ADC 2b (P = 0.03). Inter- and intrareader agreement was excellent for ADC, D, and f. In PAC, D negatively correlates with fibrosis, with a trend toward positive correlation with f suggesting both perfusion and diffusion effects contribute to stromal desmoplasia. ADC 2b is significantly lower in tumors with dense fibrosis and may serve as a biomarker of fibrosis architecture. 1 Technical Efficacy: Stage 2 J. MAGN. RESON. IMAGING 2017;46:393-402. © 2017 International Society for Magnetic Resonance in Medicine.

Grading of Gliomas by Using Monoexponential, Biexponential, and Stretched Exponential Diffusion-weighted MR Imaging and Diffusion Kurtosis MR Imaging

PubMed Central

Bai, Yan; Lin, Yusong; Tian, Jie; Shi, Dapeng; Cheng, Jingliang; Haacke, E. Mark; Hong, Xiaohua; Ma, Bo; Zhou, Jinyuan

2016-01-01

Purpose To quantitatively compare the potential of various diffusion parameters obtained from monoexponential, biexponential, and stretched exponential diffusion-weighted imaging models and diffusion kurtosis imaging in the grading of gliomas. Materials and Methods This study was approved by the local ethics committee, and written informed consent was obtained from all subjects. Both diffusion-weighted imaging and diffusion kurtosis imaging were performed in 69 patients with pathologically proven gliomas by using a 3-T magnetic resonance (MR) imaging unit. An isotropic apparent diffusion coefficient (ADC), true ADC, pseudo-ADC, and perfusion fraction were calculated from diffusion-weighted images by using a biexponential model. A water molecular diffusion heterogeneity index and distributed diffusion coefficient were calculated from diffusion-weighted images by using a stretched exponential model. Mean diffusivity, fractional anisotropy, and mean kurtosis were calculated from diffusion kurtosis images. All values were compared between high-grade and low-grade gliomas by using a Mann-Whitney U test. Receiver operating characteristic and Spearman rank correlation analysis were used for statistical evaluations. Results ADC, true ADC, perfusion fraction, water molecular diffusion heterogeneity index, distributed diffusion coefficient, and mean diffusivity values were significantly lower in high-grade gliomas than in low-grade gliomas (U = 109, 56, 129, 6, 206, and 229, respectively; P < .05). Pseudo-ADC and mean kurtosis values were significantly higher in high-grade gliomas than in low-grade gliomas (U = 98 and 8, respectively; P < .05). Both water molecular diffusion heterogeneity index (area under the receiver operating characteristic curve [AUC] = 0.993) and mean kurtosis (AUC = 0.991) had significantly greater AUC values than ADC (AUC = 0.866), mean diffusivity (AUC = 0.722), and fractional anisotropy (AUC = 0.500) in the differentiation of low-grade and high-grade gliomas (P < .05). Conclusion Water molecular diffusion heterogeneity index and mean kurtosis values may provide additional information and improve the grading of gliomas compared with conventional diffusion parameters. © RSNA, 2015 Online supplemental material is available for this article. PMID:26230975

Clinical applications and characteristics of apparent diffusion coefficient maps for the brain of two dogs.

PubMed

Kim, Boeun; Yi, Kangjae; Jung, Sunyoung; Ji, Seoyeon; Choi, Mincheol; Yoon, Junghee

2014-01-01

Diffusion-weighted imaging (DWI) and apparent diffusion coefficient (ADC) mapping are functional magnetic resonance imaging techniques for detecting water diffusion. DWI and the ADC map were performed for intracranial lesions in two dogs. In necrotizing leukoencephalitis, cavitated lesions contained a hypointense center with a hyperintense periphery on DWI, and hyperintense signals on the ADC maps. In metastatic sarcoma, masses including a necrotic region were hypointense with DWI, and hyperintense on the ADC map with hyperintense perilesional edema on DWI and ADC map. Since DWI and ADC data reflect the altered water diffusion, they can provide additional information at the molecular level.

Arginine Decarboxylase Is Localized in Chloroplasts.

PubMed Central

Borrell, A.; Culianez-Macia, F. A.; Altabella, T.; Besford, R. T.; Flores, D.; Tiburcio, A. F.

1995-01-01

Plants, unlike animals, can use either ornithine decarboxylase or arginine decarboxylase (ADC) to produce the polyamine precursor putrescine. Lack of knowledge of the exact cellular and subcellular location of these enzymes has been one of the main obstacles to our understanding of the biological role of polyamines in plants. We have generated polyclonal antibodies to oat (Avena sativa L.) ADC to study the spatial distribution and subcellular localization of ADC protein in different oat tissues. By immunoblotting and immunocytochemistry, we show that ADC is organ specific. By cell fractionation and immunoblotting, we show that ADC is localized in chloroplasts associated with the thylakoid membrane. The results also show that increased levels of ADC protein are correlated with high levels of ADC activity and putrescine in osmotically stressed oat leaves. A model of compartmentalization for the arginine pathway and putrescine biosynthesis in active photosynthetic tissues has been proposed. In the context of endosymbiote-driven metabolic evolution in plants, the location of ADC in the chloroplast compartment may have major evolutionary significance, since it explains (a) why plants can use two alternative pathways for putrescine biosynthesis and (b) why animals do not possess ADC. PMID:12228631

Incremental Prognostic Value of Apparent Diffusion Coefficient Histogram Analysis in Head and Neck Squamous Cell Carcinoma.

PubMed

Li, Xiaoxia; Yuan, Ying; Ren, Jiliang; Shi, Yiqian; Tao, Xiaofeng

2018-03-26

We aimed to investigate the incremental prognostic value of apparent diffusion coefficient (ADC) histogram analysis in patients with head and neck squamous cell carcinoma (HNSCC) and integrate it into a multivariate prognostic model. A retrospective review of magnetic resonance imaging findings was conducted in patients with pathologically confirmed HNSCC between June 2012 and December 2015. For each tumor, six histogram parameters were derived: the 10th, 50th, and 90th percentiles of ADC (ADC 10 , ADC 50 , and ADC 90 ); mean ADC values (ADC mean ); kurtosis; and skewness. The clinical variables included age, sex, smoking status, tumor volume, and tumor node metastasis stage. The association of these histogram and clinical variables with overall survival (OS) was determined. Further validation of the histogram parameters as independent biomarkers was performed using multivariate Cox proportional hazard models combined with clinical variables, which was compared to the clinical model. Models were assessed with C index and receiver operating characteristic curve analyses for the 12- and 36-month OS. Ninety-six patients were eligible for analysis. Median follow-up was 877 days (range, 54-1516 days). A total of 29 patients died during follow-up (30%). Patients with higher ADC values (ADC 10  > 0.958 × 10 -3 mm 2 /s, ADC 50  > 1.089 × 10 -3 mm 2 /s, ADC 90  > 1.152 × 10 -3 mm 2 /s, ADC mean  > 1.047 × 10 -3 mm 2 /s) and lower kurtosis (≤0.967) were significant predictors of poor OS (P < .100 for all). After adjusting for sex and tumor node metastasis stage, the ADC 90 and kurtosis are both significant predictors of OS with hazard ratios = 1.00 (95% confidence interval: 1.001-1.004) and 0.58 (95% confidence interval: 0.37-0.90), respectively. By adding the ADC parameters into the clinical model, the C index and diagnostic accuracies for the 12- and 36-month OS showed significant improvement. ADC histogram analysis has incremental prognostic value in patients with HNSCC and increases the performance of a multivariable prognostic model in addition to clinical variables. Copyright © 2018 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.

Staging of pelvic lymph nodes in patients with prostate cancer: Usefulness of multiple b value SE-EPI diffusion-weighted imaging on a 3.0 T MR system.

PubMed

Vallini, Valentina; Ortori, Simona; Boraschi, Piero; Manassero, Francesca; Gabelloni, Michela; Faggioni, Lorenzo; Selli, Cesare; Bartolozzi, Carlo

2016-01-01

To evaluate the usefulness of diffusion-weighted imaging (DWI) with a multiple b value SE-EPI sequence on a 3.0 T MR scanner for staging of pelvic lymph nodes in patients with prostate cancer candidate to radical prostatectomy and extended pelvic lymph node dissection (PLND). Institutional review board approval was obtained and written informed consent was taken from all enrolled subjects. A series of 26 patients with pathologically proven prostate cancer (high or intermediate risk according to D'Amico risk groups) scheduled for radical prostatectomy and PLND underwent 3 T MRI before surgery. DWI was performed using an axial respiratory-triggered spin-echo echo-planar sequence with multiple b values (500, 800, 1000, 1500 s/mm(2)) in all diffusion directions. ADC values were calculated by means of dedicated software fitting the curve obtained from the corresponding ADC for each b value. Fitted ADC measurements were performed at the level of proximal and distal external iliac, internal iliac, and obturator nodal stations bilaterally. Lymph node appearance was also assessed in terms of short axis, long-to-short axis ratio, node contour and intranodal heterogeneity of signal intensity. A total of 173 lymph nodes and 104 nodal stations were evaluated on DWI and pathologically analysed. Mean fitted ADC values were 0.79 ± 0.14 × 10(-3) mm(2)/s for metastatic lymph nodes and 1.13 ± 0.29 × 10(-3) mm(2)/s in non-metastatic ones (P < 0.0001). The cut-off for fitted ADC obtained by ROC curve analysis was 0.91 × 10(-3) mm(2)/s. A two-point-level score was assigned for each qualitative parameter, and the mean grading score was 6.09 ± 0.61 for metastastic lymph nodes and 5.42 ± 0.79 for non-metastatic ones, respectively (P = 0.001). Using a score threshold of 4 for morphological, structural, and dimensional MRI analysis and a cut--off value of 0.91 × 10(-3) mm(2)/s for fitted ADC measurements of pelvic lymph nodes, per--station sensitivity, specificity, PPV, NPV and diagnostic accuracy were 100%, 7.9%, 15.6%, 100% and 21.3%, and 84.6%, 89.5%, 57.9%, 97.1% and 88.8%, respectively. 3.0T DWI with a multiple b value SE-EPI sequence may help distinguish benign from malignant pelvic lymph nodes in patients with prostate cancer.

Whole-tumour diffusion kurtosis MR imaging histogram analysis of rectal adenocarcinoma: Correlation with clinical pathologic prognostic factors.

PubMed

Cui, Yanfen; Yang, Xiaotang; Du, Xiaosong; Zhuo, Zhizheng; Xin, Lei; Cheng, Xintao

2018-04-01

To investigate potential relationships between diffusion kurtosis imaging (DKI)-derived parameters using whole-tumour volume histogram analysis and clinicopathological prognostic factors in patients with rectal adenocarcinoma. 79 consecutive patients who underwent MRI examination with rectal adenocarcinoma were retrospectively evaluated. Parameters D, K and conventional ADC were measured using whole-tumour volume histogram analysis. Student's t-test or Mann-Whitney U-test, receiver operating characteristic curves and Spearman's correlation were used for statistical analysis. Almost all the percentile metrics of K were correlated positively with nodal involvement, higher histological grades, the presence of lymphangiovascular invasion (LVI) and circumferential margin (CRM) (p<0.05), with the exception of between K 10th , K 90th and histological grades. In contrast, significant negative correlations were observed between 25th, 50th percentiles and mean values of ADC and D, as well as ADC 10th , with tumour T stages (p< 0.05). Meanwhile, lower 75th and 90th percentiles of ADC and D values were also correlated inversely with nodal involvement (p< 0.05). K mean showed a relatively higher area under the curve (AUC) and higher specificity than other percentiles for differentiation of lesions with nodal involvement. DKI metrics with whole-tumour volume histogram analysis, especially K parameters, were associated with important prognostic factors of rectal cancer. • K correlated positively with some important prognostic factors of rectal cancer. • K mean showed higher AUC and specificity for differentiation of nodal involvement. • DKI metrics with whole-tumour volume histogram analysis depicted tumour heterogeneity.

Seroprevalence of Neutralizing Antibodies against Human Adenovirus Type-5 and Chimpanzee Adenovirus Type-68 in Cancer Patients.

PubMed

Zhao, Hua; Xu, Can; Luo, Xiaoli; Wei, Feng; Wang, Ning; Shi, Huiying; Ren, Xiubao

2018-01-01

Since the preclinical results about chimpanzee adenovirus serotype-68 (AdC68)-based vaccine showed an encouraging results, it reminded us that AdC68 may be a suitable cancer vaccine vector. Previous study indicated that the seroprevalence of neutralizing antibodies (NAbs) against adenovirus was different between cancer patients and healthy volunteers. Knowledge regarding the prevalence rates of AdC68 NAbs for cancer patients is lacking. Therefore, assessing the preexistence of NAbs against AdC68 in cancer patients could provide useful insights for developing future AdC68-based cancer vaccines. In this study, 440 patients with different pathological types of tumors and 204 healthy adult volunteers were enrolled to evaluate the NAbs against AdC68 and human adenovirus serotype-5 (AdHu5). The seroprevalence of NAbs against AdC68 was much lower than that against AdHu5 in cancer subjects (43.64 vs. 67.05%, P  < 0.01). The seroprevalence rates of NAbs to AdC68 in the cancer subjects were statistically higher than those detected in the healthy adult volunteers (43.64 vs. 23.53%, P  = 0.000). The seroprevalence rates of AdC68 NAbs were much lower in lung, laryngeal, esophageal, and cervical cancer patients compared with oropharyngeal, colon, and rectal cancer patients. Furthermore, the seroprevalence rates of AdC68 NAbs were much lower in lung adenocarcinoma patients than in lung squamous cell carcinoma patients (35.00 vs. 70.00%, P  < 0.05). No significant difference in the AdC68 NAbs among patients with different clinical stages of cancer was detected. The percentage of NAbs against AdC68 was significantly lower than that against AdHu5 ( P  < 0.05) in stage-I, -II, and -III cancer patients. No significant difference between the percentage of NAbs against AdC68 and AdHu5 in the subjects with stage-IV cancer was detected. The study also demonstrated the distribution of AdHu5 and AdC68 NAb titers for the positive samples. It showed that very low NAb titers against AdC68 with respect to AdHu5 in both healthy subjects and cancer subjects, especially in lung, laryngeal, esophageal, gastric, and cervical carcinomas. Also, the titer of NAbs against AdC68 was significantly lower than that against AdHu5 in the same clinical stage and age group ( P  < 0.05). Taken together, the present study showed that NAbs against AdC68 is much lower than AdHu5, especially in lung adenocarcinoma, laryngeal cancer, esophageal cancer, and cervical cancer patients. These results provided strong support for candidating AdC68 as a suitable vector of cancer vaccines.

Apparent diffusion coefficient of vertebral haemangiomas allows differentiation from malignant focal deposits in whole-body diffusion-weighted MRI.

PubMed

Winfield, Jessica M; Poillucci, Gabriele; Blackledge, Matthew D; Collins, David J; Shah, Vallari; Tunariu, Nina; Kaiser, Martin F; Messiou, Christina

2018-04-01

The aim of this study was to identify apparent diffusion coefficient (ADC) values for typical haemangiomas in the spine and to compare them with active malignant focal deposits. This was a retrospective single-institution study. Whole-body magnetic resonance imaging (MRI) scans of 106 successive patients with active multiple myeloma, metastatic prostate or breast cancer were analysed. ADC values of typical vertebral haemangiomas and malignant focal deposits were recorded. The ADC of haemangiomas (72 ROIs, median ADC 1,085×10 -6 mm 2 s -1 , interquartile range 927-1,295×10 -6 mm 2 s -1 ) was significantly higher than the ADC of malignant focal deposits (97 ROIs, median ADC 682×10 -6 mm 2 s -1 , interquartile range 583-781×10 -6 mm 2 s -1 ) with a p-value < 10 -6 . Receiver operating characteristic (ROC) analysis produced an area under the curve of 0.93. An ADC threshold of 872×10 -6 mm 2 s -1 separated haemangiomas from malignant focal deposits with a sensitivity of 84.7 % and specificity of 91.8 %. ADC values of classical vertebral haemangiomas are significantly higher than malignant focal deposits. The high ADC of vertebral haemangiomas allows them to be distinguished visually and quantitatively from active sites of disease, which show restricted diffusion. • Whole-body diffusion-weighted MRI is becoming widely used in myeloma and bone metastases. • ADC values of vertebral haemangiomas are significantly higher than malignant focal deposits. • High ADCs of haemangiomas allows them to be distinguished from active disease.

Virtual Sensor Test Instrumentation

NASA Technical Reports Server (NTRS)

Wang, Roy

2011-01-01

Virtual Sensor Test Instrumentation is based on the concept of smart sensor technology for testing with intelligence needed to perform sell-diagnosis of health, and to participate in a hierarchy of health determination at sensor, process, and system levels. A virtual sensor test instrumentation consists of five elements: (1) a common sensor interface, (2) microprocessor, (3) wireless interface, (4) signal conditioning and ADC/DAC (analog-to-digital conversion/ digital-to-analog conversion), and (5) onboard EEPROM (electrically erasable programmable read-only memory) for metadata storage and executable software to create powerful, scalable, reconfigurable, and reliable embedded and distributed test instruments. In order to maximize the efficient data conversion through the smart sensor node, plug-and-play functionality is required to interface with traditional sensors to enhance their identity and capabilities for data processing and communications. Virtual sensor test instrumentation can be accessible wirelessly via a Network Capable Application Processor (NCAP) or a Smart Transducer Interlace Module (STIM) that may be managed under real-time rule engines for mission-critical applications. The transducer senses the physical quantity being measured and converts it into an electrical signal. The signal is fed to an A/D converter, and is ready for use by the processor to execute functional transformation based on the sensor characteristics stored in a Transducer Electronic Data Sheet (TEDS). Virtual sensor test instrumentation is built upon an open-system architecture with standardized protocol modules/stacks to interface with industry standards and commonly used software. One major benefit for deploying the virtual sensor test instrumentation is the ability, through a plug-and-play common interface, to convert raw sensor data in either analog or digital form, to an IEEE 1451 standard-based smart sensor, which has instructions to program sensors for a wide variety of functions. The sensor data is processed in a distributed fashion across the network, providing a large pool of resources in real time to meet stringent latency requirements.

Improved differentiation between hepatic hemangioma and metastases on diffusion-weighted MRI by measurement of standard deviation of apparent diffusion coefficient.

PubMed

Hardie, Andrew D; Egbert, Robert E; Rissing, Michael S

2015-01-01

Diffusion-weighted magnetic resonance imaging (DW-MR) can be useful in the differentiation of hemangiomata from liver metastasis, but improved methods other than by mean apparent diffusion coefficient (mADC) are needed. A retrospective review identified 109 metastatic liver lesions and 86 hemangiomata in 128 patients who had undergone DW-MR. For each lesion, mADC and the standard deviation of the mean ADC (sdADC) were recorded and compared by receiver operating characteristic analysis. Mean mADC was higher in benign hemangiomata (1.52±0.12 mm(2)/s) than in liver metastases (1.33±0.18 mm(2)/s), but there was significant overlap in values. The mean sdADC was lower in hemangiomata (101±17 mm(2)/s) than metastases (245±25 mm(2)/s) and demonstrated no overlap in values, which was significantly different (P<.0001). Hemangiomata may be better able to be differentiated from liver metastases on the basis of sdADC than by mADC, although further studies are needed. Copyright © 2015 Elsevier Inc. All rights reserved.

Antibody drug conjugates - Trojan horses in the war on cancer.

PubMed

Iyer, U; Kadambi, V J

2011-01-01

Antibody drug conjugates (ADCs) consist of an antibody attached to a cytotoxic drug by means of a linker. ADCs provide a way to couple the specificity of a monoclonal antibody (mAb) to the cytotoxicity of a small-molecule drug and, therefore, are promising new therapies for cancer. ADCs are prodrugs that are inactive in circulation but exert their cytotoxicity upon binding to the target cancer cell. Earlier unsuccessful attempts to generate ADCs with therapeutic value have emphasized the important role each component plays in determining the efficacy and safety of the final ADC. Scientific advances in engineering antibodies for maximum efficacy as anticancer agents, identification of highly cytotoxic molecules, and generation of linkers with increased stability in circulation have all contributed to the development of the many ADCs that are currently in clinical trials. This review discusses parameters that guide the selection of the components of an ADC to increase its therapeutic window, provides a brief look at ADCs currently in clinical trials, and discusses future challenges in this field. Copyright © 2011. Published by Elsevier Inc.

Localization of arginine decarboxylase in tobacco plants.

PubMed

Bortolotti, Cristina; Cordeiro, Alexandra; Alcázar, Rubén; Borrell, Antoni; Culiañez-Macià, Francisco A.; Tiburcio, Antonio F.; Altabella, Teresa

2004-01-01

The lack of knowledge about the tissue and subcellular distribution of polyamines (PAs) and the enzymes involved in their metabolism remains one of the main obstacles in our understanding of the biological role of PAs in plants. Arginine decarboxylase (ADC; EC 4.1.1.9) is a key enzyme in polyamine biosynthesis in plants. We have characterized a cDNA coding for ADC from Nicotiana tabacum L. cv. Petit Havana SR1. The deduced ADC polypeptide had 721 amino acids and a molecular mass of 77 kDa. The ADC cDNA was overexpressed in Escherichia coli, and the ADC fusion protein obtained was used to produce polyclonal antibodies. Using immunological methods, we demonstrate the presence of the ADC protein in all plant organs analysed: flowers, seeds, stems, leaves and roots. Moreover, depending on the tissue, the protein is localized in two different subcellular compartments, the nucleus and the chloroplast. In photosynthetic tissues, ADC is located mainly in chloroplasts, whereas in non-photosynthetic tissues the protein appears to be located in nuclei. The different compartmentation of ADC may be related to distinct functions of the protein in different cell types.

Evaluation of diffusivity in the anterior lobe of the pituitary gland: 3D turbo field echo with diffusion-sensitized driven-equilibrium preparation.

PubMed

Hiwatashi, A; Yoshiura, T; Togao, O; Yamashita, K; Kikuchi, K; Kobayashi, K; Ohga, M; Sonoda, S; Honda, H; Obara, M

2014-01-01

3D turbo field echo with diffusion-sensitized driven-equilibrium preparation is a non-echo-planar technique for DWI, which enables high-resolution DWI without field inhomogeneity-related image distortion. The purpose of this study was to evaluate the feasibility of diffusion-sensitized driven-equilibrium turbo field echo in evaluating diffusivity in the normal pituitary gland. First, validation of diffusion-sensitized driven-equilibrium turbo field echo was attempted by comparing it with echo-planar DWI. Five healthy volunteers were imaged by using diffusion-sensitized driven-equilibrium turbo field echo and echo-planar DWI. The imaging voxel size was 1.5 × 1.5 × 1.5 mm(3) for diffusion-sensitized driven-equilibrium turbo field echo and 1.5 × 1.9 × 3.0 mm(3) for echo-planar DWI. ADCs measured by the 2 methods in 15 regions of interests (6 in gray matter and 9 in white matter) were compared by using the Pearson correlation coefficient. The ADC in the pituitary anterior lobe was then measured in 10 volunteers by using diffusion-sensitized driven-equilibrium turbo field echo, and the results were compared with those in the pons and vermis by using a paired t test. The ADCs from the 2 methods showed a strong correlation (r = 0.79; P < .0001), confirming the accuracy of the ADC measurement with the diffusion-sensitized driven-equilibrium sequence. The ADCs in the normal pituitary gland were 1.37 ± 0.13 × 10(-3) mm(2)/s, which were significantly higher than those in the pons (1.01 ± 0.24 × 10(-3) mm(2)/s) and the vermis (0.89 ± 0.25 × 10(-3) mm(2)/s, P < .01). We demonstrated that diffusion-sensitized driven-equilibrium turbo field echo is feasible in assessing ADC in the pituitary gland.

Apparent diffusion coefficient measurement of ovarian stroma: A potential tool for the diagnosis of polycystic ovary syndrome.

PubMed

Samanci, C; Alis, D; Ustabasioglu, F E; Ozmen, E; Ucar, A K; Aslan, M; Habibi, H A; Bakan, S; Ozcabi, B; Evliyaoğlu, S O; Adaletli, I

2017-01-01

The purpose of this study was to assess the diagnostic value of measuring the apparent diffusion coefficient (ADC) of ovarian stroma in polycystic ovary syndrome (PCOS). This study was approved by the institutional review board and informed consent was obtained from each women. A total of 17 women (mean age, 22.2 years±5.1 [SD]; range, 16-33 years) with a diagnosis of PCOS according to the Androgen Excess and PCOS Society criteria and 18 healthy women (mean age, 22.8 years±5.2 [SD]; range, 16-31 years) who served as a control group were included in this prospective study. ADC values of the ovarian stroma during the early follicular phase were calculated by two observers in the two groups. Comparisons were performed using the Student t-test. The mean ADC value in woman with PCOS (1.29±0.27×10 -3  mm 2 /s; range: 0.59×10 -3 - 1.88×10 -3  mm 2 /s) was significantly lower than that in the control group (1.48±0.17×10 -3 mm 2 /s; range: 1.12×10 -3 - 1.86×10 -3 mm 2 /s) (P<0.001). The ADC cutoff value for the determination of PCOS with maximum accuracy was 1.38×10 -3  mm 2 /s (AUC: 0.720; 95% CI: 0.597, 0.843), yielding 78% sensitivity and 62.9% specificity. ADC values of ovarian stroma are lower in patients with PCOS than in control subjects. ADC measurement of ovarian stroma in women with PCOS might help improve the diagnosis of PCOS. Copyright © 2016 Éditions françaises de radiologie. Published by Elsevier Masson SAS. All rights reserved.

Subgrid parameterization of snow distribution at a Mediterranean site using terrestrial photography

NASA Astrophysics Data System (ADS)

Pimentel, Rafael; Herrero, Javier; José Polo, María

2017-02-01

Subgrid variability introduces non-negligible scale effects on the grid-based representation of snow. This heterogeneity is even more evident in semiarid regions, where the high variability of the climate produces various accumulation melting cycles throughout the year and a large spatial heterogeneity of the snow cover. This variability in a watershed can often be represented by snow accumulation-depletion curves (ADCs). In this study, terrestrial photography (TP) of a cell-sized area (30 × 30 m) was used to define local snow ADCs at a Mediterranean site. Snow-cover fraction (SCF) and snow-depth (h) values obtained with this technique constituted the two datasets used to define ADCs. A flexible sigmoid function was selected to parameterize snow behaviour on this subgrid scale. It was then fitted to meet five different snow patterns in the control area: one for the accumulation phase and four for the melting phase in a cycle within the snow season. Each pattern was successfully associated with the snow conditions and previous evolution. The resulting ADCs were associated to certain physical features of the snow, which were used to incorporate them in the point snow model formulated by Herrero et al. (2009) by means of a decision tree. The final performance of this model was tested against field observations recorded over four hydrological years (2009-2013). The calibration and validation of this ADC snow model was found to have a high level of accuracy, with global RMSE values of 105.8 mm for the average snow depth and 0.21 m2 m-2 for the snow-cover fraction in the control area. The use of ADCs on the cell scale proposed in this research provided a sound basis for the extension of point snow models to larger areas by means of a gridded distributed calculation.

Comparison of Free-Breathing With Navigator-Triggered Technique in Diffusion Weighted Imaging for Evaluation of Small Hepatocellular Carcinoma: Effect on Image Quality and Intravoxel Incoherent Motion Parameters.

PubMed

Shan, Yan; Zeng, Meng-su; Liu, Kai; Miao, Xi-Yin; Lin, Jiang; Fu, Cai xia; Xu, Peng-ju

2015-01-01

To evaluate the effect on image quality and intravoxel incoherent motion (IVIM) parameters of small hepatocellular carcinoma (HCC) from choice of either free-breathing (FB) or navigator-triggered (NT) diffusion-weighted (DW) imaging. Thirty patients with 37 small HCCs underwent IVIM DW imaging using 12 b values (0-800 s/mm) with 2 sequences: NT, FB. A biexponential analysis with the Bayesian method yielded true diffusion coefficient (D), pseudodiffusion coefficient (D*), and perfusion fraction (f) in small HCCs and liver parenchyma. Apparent diffusion coefficient (ADC) was also calculated. The acquisition time and image quality scores were assessed for 2 sequences. Independent sample t test was used to compare image quality, signal intensity ratio, IVIM parameters, and ADC values between the 2 sequences; reproducibility of IVIM parameters, and ADC values between 2 sequences was assessed with the Bland-Altman method (BA-LA). Image quality with NT sequence was superior to that with FB acquisition (P = 0.02). The mean acquisition time for FB scheme was shorter than that of NT sequence (6 minutes 14 seconds vs 10 minutes 21 seconds ± 10 seconds P < 0.01). The signal intensity ratio of small HCCs did not vary significantly between the 2 sequences. The ADC and IVIM parameters from the 2 sequences show no significant difference. Reproducibility of D*and f parameters in small HCC was poor (BA-LA: 95% confidence interval, -180.8% to 189.2% for D* and -133.8% to 174.9% for f). A moderate reproducibility of D and ADC parameters was observed (BA-LA: 95% confidence interval, -83.5% to 76.8% for D and -74.4% to 88.2% for ADC) between the 2 sequences. The NT DW imaging technique offers no advantage in IVIM parameters measurements of small HCC except better image quality, whereas FB technique offers greater confidence in fitted diffusion parameters for matched acquisition periods.

Milatuzumab-SN-38 conjugates for the treatment of CD74+ cancers.

PubMed

Govindan, Serengulam V; Cardillo, Thomas M; Sharkey, Robert M; Tat, Fatma; Gold, David V; Goldenberg, David M

2013-06-01

CD74 is an attractive target for antibody-drug conjugates (ADC), because it internalizes and recycles after antibody binding. CD74 mostly is associated with hematologic tumors but is expressed also in solid cancers. Therefore, ADCs of the humanized anti-CD74 antibody, milatuzumab, were examined for the therapy of CD74-expressing solid tumors. Milatuzumab-doxorubicin and two milatuzumab-SN-38 conjugates with cleavable linkers, differing in their stability in serum and how they release SN-38 in the lysosome, were prepared. CD74 expression was determined by flow cytometry and immunohistology. In vitro cytotoxicity and in vivo therapeutic studies were conducted in the human cancer cell lines A-375 (melanoma), HuH-7 and Hep-G2 (hepatoma), Capan-1 (pancreatic), NCI-N87 (gastric), and Raji Burkitt lymphoma. The milatuzumab-SN-38 ADC was compared with SN-38 ADCs prepared with anti-Trop-2 and anti-CEACAM6 antibodies in xenografts expressing their target antigens. Milatuzumab-doxorubicin was most effective in the lymphoma model, whereas in A-375 and Capan-1 solid tumors, only milatuzumab-SN-38 showed a therapeutic benefit. Despite much lower surface expression of CD74 than Trop-2 or CEACAM6, milatuzumab-SN-38 had similar efficacy in Capan-1 as anti-Trop-2-SN-38, but in NCI-N87, anti-CEACAM6 and anti-Trop-2 conjugates were superior. Studies in two hepatoma lines at a single dose level showed significant benefit over saline controls but not against an irrelevant immunoglobulin G conjugate. CD74 is a suitable target for ADCs in some solid tumor xenografts, with efficacy largely influenced by uniformity of CD74 expression and with SN-38 conjugates providing the best therapeutic responses; SN-38 conjugates were preferable in solid cancers, whereas doxorubicin ADC was better in lymphoma tested. ©2013 AACR

Drug-to-antibody determination for an antibody-drug-conjugate utilizing cathepsin B digestion coupled with reversed-phase high-pressure liquid chromatography analysis.

PubMed

Adamo, Michael; Sun, Guoyong; Qiu, Difei; Valente, Joseph; Lan, Wenkui; Song, Hangtian; Bolgar, Mark; Katiyar, Amit; Krishnamurthy, Girija

2017-01-20

Antibody drug conjugates or ADCs are currently being evaluated for their effectiveness as targeted chemotherapeutic agents across the pharmaceutical industry. Due to the complexity arising from the choice of antibody, drug and linker; analytical methods for release and stability testing are required to provide a detailed understanding of both the antibody and the drug during manufacturing and storage. The ADC analyzed in this work consists of a tubulysin drug analogue that is randomly conjugated to lysine residues in a human IgG1 antibody. The drug is attached to the lysine residue through a peptidic, hydrolytically stable, cathepsin B cleavable linker. The random lysine conjugation produces a heterogeneous mixture of conjugated species with a variable drug-to-antibody ratio (DAR), therefore, the average amount of drug attached to the antibody is a critical parameter that needs to be monitored. In this work we have developed a universal method for determining DAR in ADCs that employ a cathepsin B cleavable linker. The ADC is first cleaved at the hinge region and then mildly reduced prior to treatment with the cathepsin B enzyme to release the drug from the antibody fragments. This pre-treatment allows the cathepsin B enzyme unrestricted access to the cleavage sites and ensures optimal conditions for the cathepsin B to cleave all the drug from the ADC molecule. The cleaved drug is then separated from the protein components by reversed phase high performance liquid chromatography (RP-HPLC) and quantitated using UV absorbance. This method affords superior cleavage efficiency to other methods that only employ a cathepsin digestion step as confirmed by mass spectrometry analysis. This method was shown to be accurate and precise for the quantitation of the DAR for two different random lysine conjugated ADC molecules. Copyright © 2016 Elsevier B.V. All rights reserved.

Additional Value of Diffusion-Weighted Imaging to Evaluate Prognostic Factors of Breast Cancer: Correlation with the Apparent Diffusion Coefficient.

PubMed

Park, Eun Kyung; Cho, Kyu Ran; Seo, Bo Kyoung; Woo, Ok Hee; Cho, Sung Bum; Bae, Jeoung Won

2016-01-01

Breast cancer is a heterogeneous disease with diverse prognoses. The main prognostic determinants are lymph node status, tumor size, histological grade, and biological factors, such as hormone receptors, human epidermal growth factor receptor 2 (HER2), Ki-67 protein levels, and p53 expression. Diffusion-weighted imaging (DWI) can be used to measure the apparent diffusion coefficient (ADC) that provides information related to tumor cellularity and the integrity of the cell membranes. The goal of this study was to evaluate whether ADC measurements could provide information on the prognostic factors of breast cancer. A total of 71 women with invasive breast cancer, treated consecutively, who underwent preoperative breast MRIs with DWI at 3.0 Tesla and subsequent surgery, were prospectively included in this study. Each DWI was acquired with b values of 0 and 1000 s/mm(2). The mean ADC values of the lesions were measured, including the entire lesion on the three largest sections. We performed histopathological analyses for the tumor size, lymph node status, histological grade, hormone receptors, human epidermal growth factor receptor 2 (HER2), Ki-67, p53, and molecular subtypes. The associations with the ADC values and prognostic factors of breast cancer were evaluated using the independent-samples t test and the one-way analysis of variance (ANOVA). A low ADC value was associated with lymph node metastasis (P < 0.01) and with high Ki-67 protein levels (P = 0.03). There were no significant differences in the ADC values among the histological grade (P = 0.48), molecular subtype (P = 0.51), tumor size (P = 0.46), and p53 protein level (P = 0.62). The pre-operative use of the 3.0 Tesla DWI could provide information about the lymph node status and tumor proliferation for breast cancer patients, and could help determine the optimal treatment plan.

76 FR 43286 - National Assessment Governing Board; Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-20

... levels for each grade and subject tested, developing standards and procedures for interstate and national... in closed session to review secure test items for the 2012 Economics assessment at grade 12 and the... meeting the ADC will complete their review of secure NAEP test items for the 2012 Economics assessment at...

Apparent diffusion coefficient value as a biomarker reflecting morphological and biological features of prostate cancer.

PubMed

Bae, Hyeyeol; Yoshida, Soichiro; Matsuoka, Yoh; Nakajima, Hiroshi; Ito, Eisaku; Tanaka, Hiroshi; Oya, Miyako; Nakayama, Takayuki; Takeshita, Hideki; Kijima, Toshiki; Ishioka, Junichiro; Numao, Noboru; Koga, Fumitaka; Saito, Kazutaka; Akashi, Takumi; Fujii, Yasuhisa; Kihara, Kazunori

2014-03-01

To assess whether there is an association between the apparent diffusion coefficient (ADC) value and the pathological characteristics of prostate cancer. The study cohort consisted of 29 consecutive patients with prostate cancer treated with radical prostatectomy. All patients underwent diffusion-weighted MRI before the prostate biopsy. In 42 tumor foci, the associations of the ADC values with the clinicopathological characteristics and Ki-67 labeling index (LI) were analyzed. High-grade cancers (Gleason score [GS] ≥ 4 + 3), larger cancers (maximum diameter (MD) ≥ 16 mm), and highly proliferating cancers (Ki-67 LI ≥ 4.43 %) had significantly lower ADC values, respectively (P < .001, P = .008, and P = .044, respectively). There was no significant difference in ADC value according to age, prostate-specific antigen, presence of extra-prostatic extension, and intra-tumoral stroma proportion. Multivariate analysis showed that GS, Ki-67 LI, and MD had independent and significant correlations with ADC value (P < .001, P = .006, and P = .002, respectively). Low ADC tumors (<0.52 × 10(-3) mm(2)/s) are likely to be high-grade cancer foci compared with high ADC tumors (relative risk: 65.2). The sensitivity and specificity of the ADC value to predict high-grade cancer foci are 81.8 and 93.5 %, respectively. A low ADC value reflects the morphological and biological features of prostate cancer. Analyzing the ADC value may make it possible to more precisely predict the cancer aggressiveness of each focus before treatment.

Age-related differences in the response of leg muscle cross-sectional area and water diffusivity measures to a period of supine rest.

PubMed

Lorbergs, Amanda L; Noseworthy, Michael D; MacIntyre, Norma J

2015-06-01

The object was to assess whether cross-sectional area (CSA) and water diffusion properties of leg muscles in young and older women change with increased time spent in supine rest. Healthy young (n = 9, aged 20-30 years) and older (n = 9, aged 65-75 years) women underwent MRI scanning of the right leg at baseline, 30 and 60 min of supine rest. Muscle CSA was derived from proton density images. Water diffusion properties [apparent diffusion coefficient (ADC) and fractional anisotropy (FA)] of the tibialis anterior and posterior, soleus, and medial and lateral heads of the gastrocnemius were derived from diffusion tensor imaging (DTI). Repeated measures ANOVAs and Bonferroni post hoc tests determined the effects of time and group on each muscle outcome. In both groups, muscle CSA and FA did not significantly change over time, whereas ADC significantly decreased. A greater decline at 30 min for young women was only observed for ADC in the medial gastrocnemius. Regardless of age, ADC values decreased with fluid shift associated with time spent supine, whereas CSA and FA were not affected. For leg muscle assessment in young and older women, DTI scanning protocols should consider the amount of time spent in a recumbent position.

The initial characterization of a revised 10-Gsps analog-to-digital converter board for radio telescopes

NASA Astrophysics Data System (ADS)

Jiango, Homin; Liuo, Howard; Guzzino, Kim

2016-07-01

In this study, the design of a 4 bit, 10-gigasamples-per-second analog-to-digital converter (ADC) printed circuit board assembly (PCBA) was revised, manufactured, and tested. It is used for digitizing radio telescopes. An Adsantec ANST7120-KMA flash ADC chip was used, as in the original design. Associated with the field-programmable gate array platform developed by the Collaboration for Astronomy Signal Processing and Electronics Research community, the developed PCBA provides data acquisition systems with a wider bandwidth and simplifies the intermediate frequency section. The current version of the PCBA exhibits an analog bandwidth of up to 10 GHz (3 dB loss), and the chip exhibits an analog bandwidth of up to 18 GHz. This facilitates second and third Nyquist sampling. The following worstcase performance parameters were obtained from the revised PCBA at over 5 GHz: spurious-free dynamic range of 12 dB, signal-to-noise and distortion ratio of 2 dB, and effective number of bits of 0.7. The design bugs in the ADC chip caused the poor performance. The vendor created a new batch run and confirmed that the ADC chips of the new batch will meet the specifications addressed in its data sheet.

Diffusion-Tensor Imaging of Thigh Muscles in Duchenne Muscular Dystrophy: Correlation of Apparent Diffusion Coefficient and Fractional Anisotropy Values With Fatty Infiltration.

PubMed

Li, Gui Dian; Liang, Ying Yin; Xu, Ping; Ling, Jian; Chen, Ying Ming

2016-04-01

The purpose of this study is to investigate the correlation of apparent diffusion coefficient (ADC) and fractional anisotropy (FA) values with fatty infiltration in the thigh muscles of patients with Duchenne muscular dystrophy (DMD) using diffusion-tensor imaging (DTI). Twenty-one boys with DMD were recruited. The grade of fatty infiltration and the ADC and FA values of four thigh muscles (rectus femoris, semitendinosus, sartorius, and gracilis) were measured, and the FA and ADC values were compared with the grade of fatty infiltration. Twenty age-matched healthy boys were enrolled as the control group. The differences in the ADC and FA values of the thigh muscles between patients with DMD and the control group were compared. The patients with DMD showed lower FA values and higher ADC values in all measured muscles when compared with the control group. The FA and ADC values were correlated with the grade of fatty infiltration. For the rectus femoris muscle, r = -0.753 and p = 0.007 for FA, and r = 0.685 and p = 0.001 for ADC. For the semitendinosus muscle, r = -0.621 and p = 0.041 for FA, and r = 0.705 and p = 0.021 for ADC. For the sartorius muscle, r = -0.662 and p = 0.027 for FA, and r = 0.701 and p = 0.017 for ADC. For the gracilis muscle, r = -0.618 and p = 0.043 for FA, and r = 0.695 and p = 0.022 for ADC. Damage to the thigh muscles in patients with DMD can be detected by ADC and FA values using DTI. DTI can be used to assess the severity of the disease.

Correlation of histogram analysis of apparent diffusion coefficient with uterine cervical pathologic finding.

PubMed

Lin, Yuning; Li, Hui; Chen, Ziqian; Ni, Ping; Zhong, Qun; Huang, Huijuan; Sandrasegaran, Kumar

2015-05-01

The purpose of this study was to investigate the application of histogram analysis of apparent diffusion coefficient (ADC) in characterizing pathologic features of cervical cancer and benign cervical lesions. This prospective study was approved by the institutional review board, and written informed consent was obtained. Seventy-three patients with cervical cancer (33-69 years old; 35 patients with International Federation of Gynecology and Obstetrics stage IB cervical cancer) and 38 patients (38-61 years old) with normal cervix or cervical benign lesions (control group) were enrolled. All patients underwent 3-T diffusion-weighted imaging (DWI) with b values of 0 and 800 s/mm(2). ADC values of the entire tumor in the patient group and the whole cervix volume in the control group were assessed. Mean ADC, median ADC, 25th and 75th percentiles of ADC, skewness, and kurtosis were calculated. Histogram parameters were compared between different pathologic features, as well as between stage IB cervical cancer and control groups. Mean ADC, median ADC, and 25th percentile of ADC were significantly higher for adenocarcinoma (p = 0.021, 0.006, and 0.004, respectively), and skewness was significantly higher for squamous cell carcinoma (p = 0.011). Median ADC was statistically significantly higher for well or moderately differentiated tumors (p = 0.044), and skewness was statistically significantly higher for poorly differentiated tumors (p = 0.004). No statistically significant difference of ADC histogram was observed between lymphovascular space invasion subgroups. All histogram parameters differed significantly between stage IB cervical cancer and control groups (p < 0.05). Distribution of ADCs characterized by histogram analysis may help to distinguish early-stage cervical cancer from normal cervix or cervical benign lesions and may be useful for evaluating the different pathologic features of cervical cancer.

Regional MRI Diffusion, White-Matter Hyperintensities, and Cognitive Function in Alzheimer's Disease and Vascular Dementia

PubMed Central

Scrascia, Federica; Quattrocchi, Carlo Cosimo; Errante, Yuri; Gangemi, Emma; Curcio, Giuseppe; Ursini, Francesca; Silvestrini, Mauro; Maggio, Paola; Beomonte Zobel, Bruno; Rossini, Paolo Maria; Pasqualetti, Patrizio; Falsetti, Lorenzo; Vernieri, Fabrizio

2016-01-01

Background and Purpose An increase in brain water diffusivity as measured using magnetic resonance imaging (MRI) has been recently reported in normal-appearing white matter (NAWM) in patients affected by cognitive impairment. However, it remains to be clarified if this reflects an overt neuronal tissue disruption that leads to degenerative or microvascular lesions. This question was addressed by comparing the regional MRI apparent diffusion coefficients (ADCs) of NAWM in patients affected by Alzheimer's disease (AD) or vascular dementia (VaD). The relationships of ADCs with the white-matter hyperintensity (WMH) burden, carotid atherosclerosis, and cognitive performance were also investigated. Methods Forty-nine AD and 31 VaD patients underwent brain MRI to assess the WMH volume and regional NAWM ADCs, neuropsychological evaluations, and carotid ultrasound to assess the plaque severity and intima-media thickness (IMT). Results Regional ADCs in NAWM did not differ between VaD and AD patients, while the WMH volume was greater in VaD than in AD patients. The ADC in the anterior corpus callosum was related to the WMH volume, while a greater carotid IMT was positively correlated with the temporal ADC and WMH volume. The memory performance was worse in patients with higher temporal ADCs. Constructional praxis scores were related to ADCs in the frontal, and occipital lobes, in the anterior and posterior corpus callosum as well as to the WMH volume. Abstract reasoning was related to frontal, parietal, and temporal ADCs. Conclusions Our data show that higher regional ADCs in NAWM are associated with microcirculatory impairment, as depicted by the WMH volume. Moreover, regional ADCs in NAWM are differently associated with the neuropsychological performances in memory, constructional praxia, and abstract reasoning domains. PMID:27074295

Putrescine biosynthesis in mammalian tissues.

PubMed Central

Coleman, Catherine S; Hu, Guirong; Pegg, Anthony E

2004-01-01

L-ornithine decarboxylase provides de novo putrescine biosynthesis in mammals. Alternative pathways to generate putrescine that involve ADC (L-arginine decarboxylase) occur in non-mammalian organisms. It has been suggested that an ADC-mediated pathway may generate putrescine via agmatine in mammalian tissues. Published evidence for a mammalian ADC is based on (i) assays using mitochondrial extracts showing production of 14CO2 from [1-14C]arginine and (ii) cloned cDNA sequences that have been claimed to represent ADC. We have reinvestigated this evidence and were unable to find any evidence supporting a mammalian ADC. Mitochondrial extracts prepared from freshly isolated rodent liver and kidney using a metrizamide/Percoll density gradient were assayed for ADC activity using L-[U-14C]-arginine in the presence or absence of arginine metabolic pathway inhibitors. Although 14CO2 was produced in substantial amounts, no labelled agmatine or putrescine was detected. [14C]Agmatine added to liver extracts was not degraded significantly indicating that any agmatine derived from a putative ADC activity was not lost due to further metabolism. Extensive searches of current genome databases using non-mammalian ADC sequences did not identify a viable candidate ADC gene. One of the putative mammalian ADC sequences appears to be derived from bacteria and the other lacks several residues that are essential for decarboxylase activity. These results indicate that 14CO2 release from [1-14C]arginine is not adequate evidence for a mammalian ADC. Although agmatine is a known constituent of mammalian cells, it can be transported from the diet. Therefore L-ornithine decarboxylase remains the only established route for de novo putrescine biosynthesis in mammals. PMID:14763899

RGD capsid modification enhances mucosal protective immunity of a non-human primate adenovirus vector expressing Pseudomonas aeruginosa OprF

PubMed Central

Krause, A; Whu, W Z; Qiu, J; Wafadari, D; Hackett, N R; Sharma, A; Crystal, R G; Worgall, S

2013-01-01

Replication-deficient adenoviral (Ad) vectors of non-human serotypes can serve as Ad vaccine platforms to circumvent pre-existing anti-human Ad immunity. We found previously that, in addition to that feature, a non-human primate-based AdC7 vector expressing outer membrane protein F of P. aeruginosa (AdC7OprF) was more potent in inducing lung mucosal and protective immunity compared to a human Ad5-based vector. In this study we analysed if genetic modification of the AdC7 fibre to display an integrin-binding arginine–glycine–aspartic acid (RGD) sequence can further enhance lung mucosal immunogenicity of AdC7OprF. Intratracheal immunization of mice with either AdC7OprF.RGD or AdC7OprF induced robust serum levels of anti-OprF immunoglobulin (Ig)G up to 12 weeks that were higher compared to immunization with the human vectors Ad5OprF or Ad5OprF.RGD. OprF-specific cellular responses in lung T cells isolated from mice immunized with AdC7OprF.RGD and AdC7OprF were similar for T helper type 1 (Th1) [interferon (IFN)-γ in CD8+ and interleukin (IL)-12 in CD4+], Th2 (IL-4, IL-5 and IL-13 in CD4+) and Th17 (IL-17 in CD4+). Interestingly, AdC7OprF.RGD induced more robust protective immunity against pulmonary infection with P. aeruginosa compared to AdC7OprF or the control Ad5 vectors. The enhanced protective immunity induced by AdC7OprF.RGD was maintained in the absence of alveolar macrophages (AM) or CD1d natural killer T cells. Together, the data suggest that addition of RGD to the fibre of an AdC7-based vaccine is useful to enhance its mucosal protective immunogenicity. PMID:23607394

TU-C-12A-05: Repeatability Study of Reduced Field-Of-View Diffusion-Weighted MRI On Human Thyroid Gland

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

Shukla-Dave, A; Lu, Y; Hatzoglou, V

2014-06-15

Purpose: To investigate the repeatability of reduced field-of-view diffusion-weighted imaging (rFOV DWI) in quantifying apparent diffusion coefficients (ADCs) for human thyroid glands in a clinical setting. Methods: Nine healthy human volunteers were enrolled and underwent 3T MRI exams. For each volunteer, 3 longitudinal exams (2 weeks apart) with 2 repetitive sessions within each exam, including rFOV and conventional full field-of-view (fFOV) DWI scans, were performed. In the acquired DWI images, a fixed-size region of interest (ROI; diameter=8mm) was placed on thyroid glands to calculate ADC. ADC was calculated using a monoexponential function with a noise correction scheme. The repeatability ofmore » ADC was assessed by using coefficient variation (CV) across sessions or exams, which was defined to be: r = 1-CV, 0 < r < 1, where CV=STD/m, STD is the standard deviation of ADC, and m is the average of ADC across sessions or exams. An experienced radiologist assessed and scored rFOV and fFOV DW images based on image characteristics (1, nondiagnostic; 2, poor; 3, satisfactory; 4, good; and 5, excellent).Analysis of variance (ANOVA) was performed to compare ADC values, CV of ADC, repeatability of ADC across sessions and exams, and radiologic scores between rFOV and fFOV DWI techniques. Results: There was no significant difference in ADC values across sessions and exams either in rFOV or fFOV DWI. The average CVs of both rFOV and fFOV DWI were less than 13%. The repeatability of ADC measurement between rFOV and fFOV DWI was not significantly different. The overall image quality was significantly higher with rFOV DWI than with fFOV DWI. Conclusion: This study suggested that ADCs from both rFOV and fFOV DWI were repeatable, but rFOV DWI had superior imaging quality for human thyroid glands in a clinical setting.« less

Design and implementation of projects with Xilinx Zynq FPGA: a practical case

NASA Astrophysics Data System (ADS)

Travaglini, R.; D'Antone, I.; Meneghini, S.; Rignanese, L.; Zuffa, M.

The main advantage when using FPGAs with embedded processors is the availability of additional several high-performance resources in the same physical device. Moreover, the FPGA programmability allows for connect custom peripherals. Xilinx have designed a programmable device named Zynq-7000 (simply called Zynq in the following), which integrates programmable logic (identical to the other Xilinx "serie 7" devices) with a System on Chip (SOC) based on two embedded ARM processors. Since both parts are deeply connected, the designers benefit from performance of hardware SOC and flexibility of programmability as well. In this paper a design developed by the Electronic Design Department at the Bologna Division of INFN will be presented as a practical case of project based on Zynq device. It is developed by using a commercial board called ZedBoard hosting a FMC mezzanine with a 12-bit 500 MS/s ADC. The Zynq FPGA on the ZedBoard receives digital outputs from the ADC and send them to the acquisition PC, after proper formatting, through a Gigabit Ethernet link. The major focus of the paper will be about the methodology to develop a Zynq-based design with the Xilinx Vivado software, enlightening how to configure the SOC and connect it with the programmable logic. Firmware design techniques will be presented: in particular both VHDL and IP core based strategies will be discussed. Further, the procedure to develop software for the embedded processor will be presented. Finally, some debugging tools, like the embedded Logic Analyzer, will be shown. Advantages and disadvantages with respect to adopting FPGA without embedded processors will be discussed.

Inter- and Intra-Observer Repeatability of Quantitative Whole-Body, Diffusion-Weighted Imaging (WBDWI) in Metastatic Bone Disease.

PubMed

Blackledge, Matthew D; Tunariu, Nina; Orton, Matthew R; Padhani, Anwar R; Collins, David J; Leach, Martin O; Koh, Dow-Mu

2016-01-01

Quantitative whole-body diffusion-weighted MRI (WB-DWI) is now possible using semi-automatic segmentation techniques. The method enables whole-body estimates of global Apparent Diffusion Coefficient (gADC) and total Diffusion Volume (tDV), both of which have demonstrated considerable utility for assessing treatment response in patients with bone metastases from primary prostate and breast cancers. Here we investigate the agreement (inter-observer repeatability) between two radiologists in their definition of Volumes Of Interest (VOIs) and subsequent assessment of tDV and gADC on an exploratory patient cohort of nine. Furthermore, each radiologist was asked to repeat his or her measurements on the same patient data sets one month later to identify the intra-observer repeatability of the technique. Using a Markov Chain Monte Carlo (MCMC) estimation method provided full posterior probabilities of repeatability measures along with maximum a-posteriori values and 95% confidence intervals. Our estimates of the inter-observer Intraclass Correlation Coefficient (ICCinter) for log-tDV and median gADC were 1.00 (0.97-1.00) and 0.99 (0.89-0.99) respectively, indicating excellent observer agreement for these metrics. Mean gADC values were found to have ICCinter = 0.97 (0.81-0.99) indicating a slight sensitivity to outliers in the derived distributions of gADC. Of the higher order gADC statistics, skewness was demonstrated to have good inter-user agreement with ICCinter = 0.99 (0.86-1.00), whereas gADC variance and kurtosis performed relatively poorly: 0.89 (0.39-0.97) and 0.96 (0.69-0.99) respectively. Estimates of intra-observer repeatability (ICCintra) demonstrated similar results: 0.99 (0.95-1.00) for log-tDV, 0.98 (0.89-0.99) and 0.97 (0.83-0.99) for median and mean gADC respectively, 0.64 (0.25-0.88) for gADC variance, 0.85 (0.57-0.95) for gADC skewness and 0.85 (0.57-0.95) for gADC kurtosis. Further investigation of two anomalous patient cases revealed that a very small proportion of voxels with outlying gADC values lead to instability in higher order gADC statistics. We therefore conclude that estimates of median/mean gADC and tumour volume demonstrate excellent inter- and intra-observer repeatability whilst higher order statistics of gADC should be used with caution when ascribing significance to clinical changes.

Optimal Parameters to Determine the Apparent Diffusion Coefficient in Diffusion Weighted Imaging via Simulation

NASA Astrophysics Data System (ADS)

Perera, Dimuthu

Diffusion weighted (DW) Imaging is a non-invasive MR technique that provides information about the tissue microstructure using the diffusion of water molecules. The diffusion is generally characterized by the apparent diffusion coefficient (ADC) parametric map. The purpose of this study is to investigate in silico how the calculation of ADC is affected by image SNR, b-values, and the true tissue ADC. Also, to provide optimal parameter combination depending on the percentage accuracy and precision for prostate peripheral region cancer application. Moreover, to suggest parameter choices for any type of tissue, while providing the expected accuracy and precision. In this research DW images were generated assuming a mono-exponential signal model at two different b-values and for known true ADC values. Rician noise of different levels was added to the DWI images to adjust the image SNR. Using the two DWI images, ADC was calculated using a mono-exponential model for each set of b-values, SNR, and true ADC. 40,000 ADC data were collected for each parameter setting to determine the mean and the standard-deviation of the calculated ADC, as well as the percentage accuracy and precision with respect to the true ADC. The accuracy was calculated using the difference between known and calculated ADC. The precision was calculated using the standard-deviation of calculated ADC. The optimal parameters for a specific study was determined when both the percentage accuracy and precision were minimized. In our study, we simulated two true ADCs (ADC 0.00102 for tumor and 0.00180 mm2/s for normal prostate peripheral region tissue). Image SNR was varied from 2 to 100 and b-values were varied from 0 to 2000s/mm2. The results show that the percentage accuracy and percentage precision were minimized with image SNR. To increase SNR, 10 signal-averagings (NEX) were used considering the limitation in total scan time. The optimal NEX combination for tumor and normal tissue for prostate peripheral region was 1: 9. Also, the minimum percentage accuracy and percentage precision were obtained when low b-value is 0 and high b-value is 800 mm2/s for normal tissue and 1400 mm2/s for tumor tissue. Results also showed that for tissues with 1 x 10-3 < ADC < 2.1 x 10-3 mm 2/s the parameter combination at SNR = 20, b-value pair 0, 800 mm 2/s with NEX = 1:9 can calculate ADC with a percentage accuracy of less than 2% and percentage precision of 6-8%. Also, for tissues with 0.6 x 10-3 < ADC < 1.25 x 10-3 mm2 /s the parameter combination at SNR = 20, b-value pair 0, 1400 mm 2/s with NEX =1:9 can calculate ADC with a percentage accuracy of less than 2% and percentage precision of 6-8%.

Attitude Determination and Control System (ADCS) and Maintenance and Diagnostic System (MDS): A maintenance and diagnostic system for Space Station Freedom

NASA Technical Reports Server (NTRS)

Toms, David; Hadden, George D.; Harrington, Jim

1990-01-01

The Maintenance and Diagnostic System (MDS) that is being developed at Honeywell to enhance the Fault Detection Isolation and Recovery system (FDIR) for the Attitude Determination and Control System on Space Station Freedom is described. The MDS demonstrates ways that AI-based techniques can be used to improve the maintainability and safety of the Station by helping to resolve fault anomalies that cannot be fully determined by built-in-test, by providing predictive maintenance capabilities, and by providing expert maintenance assistance. The MDS will address the problems associated with reasoning about dynamic, continuous information versus only about static data, the concerns of porting software based on AI techniques to embedded targets, and the difficulties associated with real-time response. An initial prototype was built of the MDS. The prototype executes on Sun and IBM PS/2 hardware and is implemented in the Common Lisp; further work will evaluate its functionality and develop mechanisms to port the code to Ada.

Diagnostic-management system and test pulse acquisition for WEST plasma measurement system

NASA Astrophysics Data System (ADS)

Wojenski, A.; Kasprowicz, G.; Pozniak, K. T.; Byszuk, A.; Juszczyk, B.; Zabolotny, W.; Zienkiewicz, P.; Chernyshova, M.; Czarski, T.; Mazon, D.; Malard, P.

2014-11-01

This paper describes current status of electronics, firmware and software development for new plasma measurement system for use in WEST facility. The system allows to perform two dimensional plasma visualization (in time) with spectrum measurement. The analog front-end is connected to Gas Electron Multiplier detector (GEM detector). The system architecture have high data throughput due to use of PCI-Express interface, Gigabit Transceivers and sampling frequency of ADC integrated circuits. The hardware is based on several years of experience in building X-ray spectrometer system for Joint European Torus (JET) facility. Data streaming is done using Artix7 FPGA devices. The system in basic configuration can work with up to 256 channels, while the maximum number of measurement channels is 2048. Advanced firmware for the FPGA is required in order to perform high speed data streaming and analog signal sampling. Diagnostic system management has been developed in order to configure measurement system, perform necessary calibration and prepare hardware for data acquisition.

Circuit design of an EMCCD camera

NASA Astrophysics Data System (ADS)

Li, Binhua; Song, Qian; Jin, Jianhui; He, Chun

2012-07-01

EMCCDs have been used in the astronomical observations in many ways. Recently we develop a camera using an EMCCD TX285. The CCD chip is cooled to -100°C in an LN2 dewar. The camera controller consists of a driving board, a control board and a temperature control board. Power supplies and driving clocks of the CCD are provided by the driving board, the timing generator is located in the control board. The timing generator and an embedded Nios II CPU are implemented in an FPGA. Moreover the ADC and the data transfer circuit are also in the control board, and controlled by the FPGA. The data transfer between the image workstation and the camera is done through a Camera Link frame grabber. The software of image acquisition is built using VC++ and Sapera LT. This paper describes the camera structure, the main components and circuit design for video signal processing channel, clock driver, FPGA and Camera Link interfaces, temperature metering and control system. Some testing results are presented.

Effects of a direct refill program for automated dispensing cabinets on medication-refill errors.

PubMed

Helmons, Pieter J; Dalton, Ashley J; Daniels, Charles E

2012-10-01

The effects of a direct refill program for automated dispensing cabinets (ADCs) on medication-refill errors were studied. This study was conducted in designated acute care areas of a 386-bed academic medical center. A wholesaler-to-ADC direct refill program, consisting of prepackaged delivery of medications and bar-code-assisted ADC refilling, was implemented in the inpatient pharmacy of the medical center in September 2009. Medication-refill errors in 26 ADCs from the general medicine units, the infant special care unit, the surgical and burn intensive care units, and intermediate units were assessed before and after the implementation of this program. Medication-refill errors were defined as an ADC pocket containing the wrong drug, wrong strength, or wrong dosage form. ADC refill errors decreased by 77%, from 62 errors per 6829 refilled pockets (0.91%) to 8 errors per 3855 refilled pockets (0.21%) (p < 0.0001). The predominant error type detected before the intervention was the incorrect medication (wrong drug, wrong strength, or wrong dosage form) in the ADC pocket. Of the 54 incorrect medications found before the intervention, 38 (70%) were loaded in a multiple-drug drawer. After the implementation of the new refill process, 3 of the 5 incorrect medications were loaded in a multiple-drug drawer. There were 3 instances of expired medications before and only 1 expired medication after implementation of the program. A redesign of the ADC refill process using a wholesaler-to-ADC direct refill program that included delivery of prepackaged medication and bar-code-assisted refill significantly decreased the occurrence of ADC refill errors.

Ischemic lesion volume determination on diffusion weighted images vs. apparent diffusion coefficient maps.

PubMed

Bråtane, Bernt Tore; Bastan, Birgul; Fisher, Marc; Bouley, James; Henninger, Nils

2009-07-07

Though diffusion weighted imaging (DWI) is frequently used for identifying the ischemic lesion in focal cerebral ischemia, the understanding of spatiotemporal evolution patterns observed with different analysis methods remains imprecise. DWI and calculated apparent diffusion coefficient (ADC) maps were serially obtained in rat stroke models (MCAO): permanent, 90 min, and 180 min temporary MCAO. Lesion volumes were analyzed in a blinded and randomized manner by 2 investigators using (i) a previously validated ADC threshold, (ii) visual determination of hypointense regions on ADC maps, and (iii) visual determination of hyperintense regions on DWI. Lesion volumes were correlated with 24 hour 2,3,5-triphenyltetrazoliumchloride (TTC)-derived infarct volumes. TTC-derived infarct volumes were not significantly different from the ADC and DWI-derived lesion volumes at the last imaging time points except for significantly smaller DWI lesions in the pMCAO model (p=0.02). Volumetric calculation based on TTC-derived infarct also correlated significantly stronger to volumetric calculation based on last imaging time point derived lesions on ADC maps than DWI (p<0.05). Following reperfusion, lesion volumes on the ADC maps significantly reduced but no change was observed on DWI. Visually determined lesion volumes on ADC maps and DWI by both investigators correlated significantly with threshold-derived lesion volumes on ADC maps with the former method demonstrating a stronger correlation. There was also a better interrater agreement for ADC map analysis than for DWI analysis. Ischemic lesion determination by ADC was more accurate in final infarct prediction, rater independent, and provided exclusive information on ischemic lesion reversibility.

Insights from native mass spectrometry approaches for top- and middle- level characterization of site-specific antibody-drug conjugates

PubMed Central

Botzanowski, Thomas; Erb, Stéphane; Hernandez-Alba, Oscar; Ehkirch, Anthony; Colas, Olivier; Wagner-Rousset, Elsa; Rabuka, David; Beck, Alain; Drake, Penelope M.; Cianférani, Sarah

2017-01-01

ABSTRACT Antibody-drug conjugates (ADCs) have emerged as a family of compounds with promise as efficient immunotherapies. First-generation ADCs were generated mostly via reactions on either lysine side-chain amines or cysteine thiol groups after reduction of the interchain disulfide bonds, resulting in heterogeneous populations with a variable number of drug loads per antibody. To control the position and the number of drug loads, new conjugation strategies aiming at the generation of more homogeneous site-specific conjugates have been developed. We report here the first multi-level characterization of a site-specific ADC by state-of-the-art mass spectrometry (MS) methods, including native MS and its hyphenation to ion mobility (IM-MS). We demonstrate the versatility of native MS methodologies for site-specific ADC analysis, with the unique ability to provide several critical quality attributes within one single run, along with a direct snapshot of ADC homogeneity/heterogeneity without extensive data interpretation. The capabilities of native IM-MS to directly access site-specific ADC conformational information are also highlighted. Finally, the potential of these techniques for assessing an ADC's heterogeneity/homogeneity is illustrated by comparing the analytical characterization of a site-specific DAR4 ADC to that of first-generation ADCs. Altogether, our results highlight the compatibility, versatility, and benefits of native MS approaches for the analytical characterization of all types of ADCs, including site-specific conjugates. Thus, we envision integrating native MS and IM-MS approaches, even in their latest state-of-the-art forms, into workflows that benchmark bioconjugation strategies. PMID:28406343

Implementation and optimization of automated dispensing cabinet technology.

PubMed

McCarthy, Bryan C; Ferker, Michael

2016-10-01

A multifaceted automated dispensing cabinet (ADC) optimization initiative at a large hospital is described. The ADC optimization project, which was launched approximately six weeks after activation of ADCs in 30 patient care unit medication rooms of a newly established adult hospital, included (1) adjustment of par inventory levels (desired on-hand quantities of medications) and par reorder quantities to reduce the risk of ADC supply exhaustion and improve restocking efficiency, (2) expansion of ADC "common stock" (medications assigned to ADC inventories) to increase medication availability at the point of care, and (3) removal of some infrequently prescribed medications from ADCs to reduce the likelihood of product expiration. The purpose of the project was to address organizational concerns regarding widespread ADC medication stockouts, growing reliance on cart-fill medication delivery systems, and suboptimal medication order turnaround times. Leveraging of the ADC technology platform's reporting functionalities for enhanced inventory control yielded a number of benefits, including cost savings resulting from reduced pharmacy technician labor requirements (estimated at $2,728 annually), a substantial reduction in the overall weekly stockout percentage (from 3.2% before optimization to 0.5% eight months after optimization), an improvement in the average medication turnaround time, and estimated cost avoidance of $19,660 attributed to the reduced potential for product expiration. Efforts to optimize ADCs through par level optimization, expansion of common stock, and removal of infrequently used medications reduced pharmacy technician labor, decreased stockout percentages, generated opportunities for cost avoidance, and improved medication turnaround times. Copyright © 2016 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

Diffusion-weighted MRI derived apparent diffusion coefficient identifies prognostically distinct subgroups of pediatric diffuse intrinsic pontine glioma.

PubMed

Lober, Robert M; Cho, Yoon-Jae; Tang, Yujie; Barnes, Patrick D; Edwards, Michael S; Vogel, Hannes; Fisher, Paul G; Monje, Michelle; Yeom, Kristen W

2014-03-01

While pediatric diffuse intrinsic pontine gliomas (DIPG) remain fatal, recent data have shown subgroups with distinct molecular biology and clinical behavior. We hypothesized that diffusion-weighted MRI can be used as a prognostic marker to stratify DIPG subsets with distinct clinical behavior. Apparent diffusion coefficient (ADC) values derived from diffusion-weighted MRI were computed in 20 consecutive children with treatment-naïve DIPG tumors. The median ADC for the cohort was used to stratify the tumors into low and high ADC groups. Survival, gender, therapy, and potential steroid effects were compared between the ADC groups. Median age at diagnosis was 6.6 (range 2.3-13.2) years, with median follow-up seven (range 1-36) months. There were 14 boys and six girls. Seventeen patients received radiotherapy, five received chemotherapy, and six underwent cerebrospinal fluid diversion. The median ADC of 1,295 × 10(-6) mm(2)/s for the cohort partitioned tumors into low or high diffusion groups, which had distinct median survivals of 3 and 13 months, respectively (log-rank p < 0.001). Low ADC tumors were found only in boys, whereas high ADC tumors were found in both boys and girls. Available tissue specimens in three low ADC tumors demonstrated high-grade histology, whereas one high ADC tumor demonstrated low-grade histology with a histone H3.1 K27M mutation and high-grade metastatic lesion at autopsy. ADC derived from diffusion-weighted MRI may identify prognostically distinct subgroups of pediatric DIPG.

Evaluating the apparent diffusion coefficient in MRI studies as a means of determining paediatric brain tumour stages.

PubMed

Domínguez-Pinilla, N; Martínez de Aragón, A; Diéguez Tapias, S; Toldos, O; Hinojosa Bernal, J; Rigal Andrés, M; González-Granado, L I

2016-09-01

The apparent diffusion coefficient (ADC) in MRI seems to be related to cellularity in brain tumours. Its utility as a tool for distinguishing between histological types and tumour stages remains controversial. We retrospectively evaluated children diagnosed with CNS tumours between January 2008 and December 2013. Data collected were age, sex, histological diagnosis, and location of the tumour. We evaluated the ADC and ADC ratio and correlated those values with histological diagnoses. The study included 55 patients with a median age of 6 years. Histological diagnoses were pilocytic astrocytoma (40%), anaplastic ependymoma (16.4%), ganglioglioma (10.9%), glioblastoma (7.3%), medulloblastoma (5.5%), and other (20%). Tumours could also be classified as low-grade (64%) or high-grade (36%). Mean ADC was 1.3 for low-grade tumours and 0.9 for high-grade tumours (p=.004). Mean ADC ratios were 1.5 and 1.2 for low and high-grade tumours respectively (p=.025). There were no significant differences in ADC/ADC ratio between different histological types. ADC and ADC ratio may be useful in imaging-study based differential diagnosis of low and high-grade tumours, but they are not a substitute for an anatomical pathology study. Copyright © 2014 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

Effects of Diffusion Time on Short-Range Hyperpolarized 3He Diffusivity Measurements in Emphysema

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

Gierada, David S.; Woods, Jason C.; Bierhals, Andrew J.

2009-09-28

Purpose: To characterize the effect of diffusion time on short-range hyperpolarized 3He MR diffusion measurements across a wide range of emphysema severity. Materials and Methods: 3He diffusion MR imaging was performed on 19 lungs or lobes resected from 18 subjects with varying degrees of emphysema using 3 diffusion times (1.6 msec, 5 msec, and 10 msec) at constant b value. Emphysema severity was quantified as the mean apparent diffusion coefficient (ADC) and as the percentage of pixels with ADC higher than multiple thresholds from 0.30-0.55 cm2/sec (ADC index). Quantitative histology (mean linear intercept) was obtained in 10 of the lungmore » specimens from 10 of the subjects. Results: The mean ADCs with diffusion times of 1.6, 5.0, and 10.0 msec were 0.46, 0.40, and 0.37 cm2/sec, respectively (P <0.0001, ANOVA). There was no relationship between the ADC magnitude and the effect of diffusion time on ADC values. Mean linear intercept correlated with ADC (r=0.91-0.94, P<0.001) and ADC index (r=0.78-0.92, P<0.01) at all diffusion times.« less

Apparent diffusion coefficient measurements in the differentiation between benign and malignant lesions: a systematic review.

PubMed

Vermoolen, M A; Kwee, T C; Nievelstein, R A J

2012-08-01

To systematically review the value of apparent diffusion coefficient (ADC) measurement in the differentiation between benign and malignant lesions. A systematic search of the Medline/Pubmed and Embase databases revealed 109 relevant studies. Quality of these articles was assessed using the Quality Assessment of the Studies of Diagnostic Accuracy Included in Systematic Reviews (QUADAS) criteria. Reported ADC values of benign and malignant lesions were compared per organ. The mean quality score of the reviewed articles was 50%. Comparison of ADC values showed marked variation among studies and between benign and malignant lesions in various organs. In several organs, such as breast, liver, and uterus, ADC values discriminated well between benign and malignant lesions. In other organs, such as the salivary glands, thyroid, and pancreas, ADCs were not significantly different between benign and malignant lesions. The potential utility of ADC measurement for the characterisation of tumours differs per organ. Future well-designed studies are required before ADC measurements can be recommended for the differentiation of benign and malignant lesions. These future studies should use standardised acquisition protocols and provide complete reporting of study methods, to facilitate comparison of results and clinical implementation of ADC measurement for tumour characterisation.

Two zinc-binding domains in the transporter AdcA from Streptococcus pyogenes facilitate high-affinity binding and fast transport of zinc.

PubMed

Cao, Kun; Li, Nan; Wang, Hongcui; Cao, Xin; He, Jiaojiao; Zhang, Bing; He, Qing-Yu; Zhang, Gong; Sun, Xuesong

2018-04-20

Zinc is an essential metal in bacteria. One important bacterial zinc transporter is AdcA, and most bacteria possess AdcA homologs that are single-domain small proteins due to better efficiency of protein biogenesis. However, a double-domain AdcA with two zinc-binding sites is significantly overrepresented in Streptococcus species, many of which are major human pathogens. Using molecular simulation and experimental validations of AdcA from Streptococcus pyogenes , we found here that the two AdcA domains sequentially stabilize the structure upon zinc binding, indicating an organization required for both increased zinc affinity and transfer speed. This structural organization appears to endow Streptococcus species with distinct advantages in zinc-depleted environments, which would not be achieved by each single AdcA domain alone. This enhanced zinc transport mechanism sheds light on the significance of the evolution of the AdcA domain fusion, provides new insights into double-domain transporter proteins with two binding sites for the same ion, and indicates a potential target of antimicrobial drugs against pathogenic Streptococcus species. © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.

Recent Results from the MicroMAS Global Environmental MonitoringNanosatellite Mission

NASA Astrophysics Data System (ADS)

Blackwell, W. J.; Cahoy, K.

2014-12-01

The Micro-sized Microwave Atmospheric Satellite (MicroMAS) is a dual-spinning 3U CubeSat equipped with apassive microwave radiometer that observes in nine channels near the 118.75-GHz oxygen absorption line.MicroMAS is designed to observe convective thunderstorms, tropical cyclones, and hurricanes from a midinclinationorbit. The MicroMAS flight unit was developed by MIT Lincoln Laboratory and the MIT Space SystemsLaboratory and was launched to the International Space Station on July 13, 2014, and scheduled for an earlySeptember deployment for a ~90-day mission. The payload is housed in the "lower" 1U of the dual-spinning 3UCubeSat and mechanically rotated approximately once per second as the spacecraft orbits the Earth, resulting in across-track scanned beam with a full-width half-max (FWHM) beamwidth of 2.4 degrees and an approximately 17-km diameter footprint at nadir incidence from a nominal altitude of 400 km. The relatively low cost of MicroMASenables the deployment of a constellation of sensors, spaced equally around several orbit planes. A small fleet ofMicroMAS systems could yield high-resolution global temperature and water vapor profiles, as well as cloudmicrophysical and precipitation parameters.Significant advancements were made in the Assembly, Integration, and Test phase of the project developmentlifecycle. The flight software and communications architecture was refined and tested in relevant lab facilities. Thepower subsystem was modified to include additional required inhibits for the ISS launch. Hardware in the loop testsas well as simulations of the attitude determination and control system (ADCS) were performed to validate theunique dual-spinning, local vertical, local horizontal (LVLH) stabilized flight design. ADCS algorithms were testedon a 3-axis air bearing and custom rig inside a 3-axis programmable Helmholtz cage. Finally, the integratedspacecraft underwent a series of environmental tests in order to verify the results of thermal modeling analyses,prove the performance of critical design components in relevant environmental conditions, and validate the softwareand concept-of-operations developed for flight. We present these advancements, lessons-learned in developing ascience-oriented CubeSat system, and any available launch/on-orbit updates.

Chemically triggered drug release from an antibody-drug conjugate leads to potent antitumour activity in mice.

PubMed

Rossin, Raffaella; Versteegen, Ron M; Wu, Jeremy; Khasanov, Alisher; Wessels, Hans J; Steenbergen, Erik J; Ten Hoeve, Wolter; Janssen, Henk M; van Onzen, Arthur H A M; Hudson, Peter J; Robillard, Marc S

2018-05-04

Current antibody-drug conjugates (ADCs) target internalising receptors on cancer cells leading to intracellular drug release. Typically, only a subset of patients with solid tumours has sufficient expression of such a receptor, while there are suitable non-internalising receptors and stroma targets. Here, we demonstrate potent therapy in murine tumour models using a non-internalising ADC that releases its drugs upon a click reaction with a chemical activator, which is administered in a second step. This was enabled by the development of a diabody-based ADC with a high tumour uptake and very low retention in healthy tissues, allowing systemic administration of the activator 2 days later, leading to efficient and selective activation throughout the tumour. In contrast, the analogous ADC comprising the protease-cleavable linker used in the FDA approved ADC Adcetris is not effective in these tumour models. This first-in-class ADC holds promise for a broader applicability of ADCs across patient populations.

A 0.9-V 12-bit 40-MSPS Pipeline ADC for Wireless Receivers

NASA Astrophysics Data System (ADS)

Ito, Tomohiko; Itakura, Tetsuro

A 0.9-V 12-bit 40-MSPS pipeline ADC with I/Q amplifier sharing technique is presented for wireless receivers. To achieve high linearity even at 0.9-V supply, the clock signals to sampling switches are boosted over 0.9V in conversion stages. The clock-boosting circuit for lifting these clocks is shared between I-ch ADC and Q-ch ADC, reducing the area penalty. Low supply voltage narrows the available output range of the operational amplifier. A pseudo-differential (PD) amplifier with two-gain-stage common-mode feedback (CMFB) is proposed in views of its wide output range and power efficiency. This ADC is fabricated in 90-nm CMOS technology. At 40MS/s, the measured SNDR is 59.3dB and the corresponding effective number of bits (ENOB) is 9.6. Until Nyquist frequency, the ENOB is kept over 9.3. The ADC dissipates 17.3mW/ch, whose performances are suitable for ADCs for mobile wireless systems such as WLAN/WiMAX.

An Analysis of Offset, Gain, and Phase Corrections in Analog to Digital Converters

NASA Astrophysics Data System (ADS)

Cody, Devin; Ford, John

2015-01-01

Many high-speed analog to digital converters (ADCs) use interwoven ADCs to greatly boost their sample rate. This interwoven architecture can introduce problems if the low speed ADCs do not have identical outputs. These errors are manifested as phantom frequencies that appear in the digitized signal although they never existed in the analog domain. Through the application of offset, gain, and phase (OGP) corrections to the ADC, this problem can be reduced. Here we report on an implementation of such a correction in a high speed ADC chip used for radio astronomy. While the corrections could not be implemented in the ADCs themselves, a partial solution was devised and implemented digitally inside of a signal processing field programmable gate array (FPGA). Positive results to contrived situations are shown, and null results are presented for implementation in an ADC083000 card with minimal error. Lastly, we discuss the implications of this method as well as its mathematical basis.

Assessment of induced rat mammary tumour response to chemotherapy using the apparent diffusion coefficient of tissue water as determined by diffusion-weighted 1H-NMR spectroscopy in vivo.

PubMed

Lemaire, L; Howe, F A; Rodrigues, L M; Griffiths, J R

1999-03-01

Chemosensitivity of N-methyl-N-nitrosourea-induced rat mammary tumours treated with 5-fluorouracil at a dose of 100 mg kg(-1) i.p. was assessed by using diffusion-weighted 1H-MRS to measure the average diffusion coefficient (ADC) of water in the tumour tissue. ADC measurements prior to any therapy correlated positively with necrotic fraction. Tumours with low initial ADC (< 0.95 x 10(9) m2 s(-1)) showed an increase in ADC 7 days after treatment, whereas tumours with a high initial ADC (> 1.2 x 10(9) m2 s(-1)) showed a decrease. All tumours decreased significantly in volume (P < 0.05) 2, 5 and 7 days after treatment. At day 7 post-treatment, tumours with a high pre-treatment ADC started to regrow. The initial ADC value, as well as changes after treatment predict tumour chemosensitivity, which could be clinically relevant.

Subcategorization of Suspicious Breast Lesions (BI-RADS Category 4) According to MRI Criteria: Role of Dynamic Contrast-Enhanced and Diffusion-Weighted Imaging.

PubMed

Maltez de Almeida, João Ricardo; Gomes, André Boechat; Barros, Thomas Pitangueira; Fahel, Paulo Eduardo; de Seixas Rocha, Mário

2015-07-01

The purposes of this study were to investigate whether dynamic contrast-enhanced MRI is adequate for subcategorization of suspicious lesions (BI-RADS category 4) and to evaluate whether use of DWI improves diagnostic performance. The study group was composed of 103 suspicious lesions found in 83 subjects. Patient ages and lesion sizes were compiled, and two radiologists reanalyzed the images; subcategorized the findings as BI-RADS 4A, 4B, or 4C; and calculated apparent diffusion coefficient (ADC) values. The stratified variables were tested by univariate analysis and inserted in two multivariate predictive models, which were used to generate ROC curves and compare AUCs. Positive predictive values (PPVs) for each subcategory and ADC level were calculated, and interobserver agreement was tested. Forty-four (42.7%) suspicious findings proved malignant. Except for age (p = 0.08), all stratified predictor variables were significant in univariate analyses (p < 0.01). Logistic regression models did not differ substantially after comparison of the ROC curves (p = 0.09), but the one including ADC values was slightly better: AUC of 0.89 (95% CI, 0.82-0.95) against AUC of 0.85 (95% CI, 0.78-0.93). PPV increased progressively in each BI-RADS 4 subcategory (4A, 0.15; 4B, 0.37; 4C, 0.84). ADC values of 1.10 × 10(-3) mm(2)/s or less had the second highest PPV (0.77). Interobserver agreement was substantial at a kappa value of 0.80 (95% CI, 0.70-0.90; p < 0.01). Risk stratification of suspicious lesions (BI-RADS category 4) can be satisfactorily performed with DCE-MRI and slightly improved when DWI is introduced.

Cardiopulmonary resuscitation duty cycle in out-of-hospital cardiac arrest.

PubMed

Johnson, Bryce V; Johnson, Bryce; Coult, Jason; Fahrenbruch, Carol; Blackwood, Jennifer; Sherman, Larry; Kudenchuk, Peter; Sayre, Michael; Rea, Thomas

2015-02-01

Duty cycle is the portion of time spent in compression relative to total time of the compression-decompression cycle. Guidelines recommend a 50% duty cycle based largely on animal investigation. We undertook a descriptive evaluation of duty cycle in human resuscitation, and whether duty cycle correlates with other CPR measures. We calculated the duty cycle, compression depth, and compression rate during EMS resuscitation of 164 patients with out-of-hospital ventricular fibrillation cardiac arrest. We captured force recordings from a chest accelerometer to measure ten-second CPR epochs that preceded rhythm analysis. Duty cycle was calculated using two methods. Effective compression time (ECT) is the time from beginning to end of compression divided by total period for that compression-decompression cycle. Area duty cycle (ADC) is the ratio of area under the force curve divided by total area of one compression-decompression cycle. We evaluated the compression depth and compression rate according to duty cycle quartiles. There were 369 ten-second epochs among 164 patients. The median duty cycle was 38.8% (SD=5.5%) using ECT and 32.2% (SD=4.3%) using ADC. A relatively shorter compression phase (lower duty cycle) was associated with greater compression depth (test for trend <0.05 for ECT and ADC) and slower compression rate (test for trend <0.05 for ADC). Sixty-one of 164 patients (37%) survived to hospital discharge. Duty cycle was below the 50% recommended guideline, and was associated with compression depth and rate. These findings provider rationale to incorporate duty cycle into research aimed at understanding optimal CPR metrics. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Astronomical catalog desk reference, 1994 edition

NASA Technical Reports Server (NTRS)

1994-01-01

The Astronomical Catalog Desk Reference is designed to aid astronomers in locating machine readable catalogs in the Astronomical Data Center (ADC) archives. The key reference components of this document are as follows: A listing of shortened titles for all catalogs available from the ADC (includes the name of the lead author and year of publication), brief descriptions of over 300 astronomical catalogs, an index of ADC catalog numbers by subject keyword, and an index of ADC catalog numbers by author. The heart of this document is the set of brief descriptions generated by the ADC staff. The 1994 edition of the Astronomical Catalog Desk Reference contains descriptions for over one third of the catalogs in the ADC archives. Readers are encouraged to refer to this section for concise summaries of those catalogs and their contents.

IVIM diffusion-weighted imaging of the liver at 3.0 T: Comparison with 1.5 T

PubMed Central

Cui, Yong; Dyvorne, Hadrien; Besa, Cecilia; Cooper, Nancy; Taouli, Bachir

2015-01-01

Purpose To compare intravoxel incoherent motion (IVIM) diffusion-weighted imaging (DWI) of the liver between 1.5 T and 3.0 T in terms of parameter quantification and inter-platform reproducibility. Materials and methods In this IRB approved prospective study, 19 subjects (17 patients with chronic liver disease and 2 healthy volunteers) underwent two repeat scans at 1.5 T and 3.0 T. Each scan included IVIM DWI using 16 b values from 0 to 800 s/mm2. A single observer measured IVIM parameters for each platform and estimated signal to noise ratio (eSNR) at b0, 200, 400 and 800 s/mm2. Wilcoxon paired tests were used to compare liver eSNR and IVIM parameters. Inter-platform reproducibility was assessed by calculating within-subject coefficient of variation (CV) and Bland–Altman limits of agreement. An ice water phantom was used to test ADC variability between the two MRI systems. Results The mean invitro difference in ADC between the two platforms was 6.8%. eSNR was significantly higher at 3.0T for all selected b values (p = 0.006–0.020), except for b0 (p = 0.239). Liver IVIM parameters were significantly different between 1.5 T and 3.0 T (p = 0.005–0.044), except for ADC (p = 0.748). The inter-platform reproducibility of true diffusion coefficient (D) and ADC were good, with mean CV of 10.9% and 11.1%, respectively. Perfusion fraction (PF) and pseudodiffusion coefficient (D*) showed more limited inter-platform reproducibility (mean CV of 22.6% for PF and 46.9% for D*). Conclusion Liver D and ADC values showed good reproducibility between 1.5 T and 3.0 T platforms; while there was more variability in PF, and large variability in D* parameters between the two platforms. These findings may have implications for drug trials assessing the role of IVIM DWI in tumor response and liver fibrosis. PMID:26393236

Assessment and quantification of sources of variability in breast apparent diffusion coefficient (ADC) measurements at diffusion weighted imaging.

PubMed

Giannotti, E; Waugh, S; Priba, L; Davis, Z; Crowe, E; Vinnicombe, S

2015-09-01

Apparent Diffusion Coefficient (ADC) measurements are increasingly used for assessing breast cancer response to neoadjuvant chemotherapy although little data exists on ADC measurement reproducibility. The purpose of this work was to investigate and characterise the magnitude of errors in ADC measures that may be encountered in such follow-up studies- namely scanner stability, scan-scan reproducibility, inter- and intra- observer measures and the most reproducible measurement of ADC. Institutional Review Board approval was obtained for the prospective study of healthy volunteers and written consent acquired for the retrospective study of patient images. All scanning was performed on a 3.0-T MRI scanner. Scanner stability was assessed using an ice-water phantom weekly for 12 weeks. Inter-scan repeatability was assessed across two scans of 10 healthy volunteers (26-61 years; mean: 44.7 years). Inter- and intra-reader analysis repeatability was measured in 52 carcinomas from clinical patients (29-70 years; mean: 50.0 years) by measuring the whole tumor ADC value on a single slice with maximum tumor diameter (ADCS) and the ADC value of a small region of interest (ROI) on the same slice (ADCmin). Repeatability was assessed using intraclass correlation coefficients (ICC) and coefficients of repeatability (CoR). Scanner stability contributed 6% error to phantom ADC measurements (0.071×10(-3)mm(2)/s; mean ADC=1.089×10(-3)mm(2)/s). The measured scan-scan CoR in the volunteers was 0.122×10(-3)mm(2)/s, contributing an error of 8% to the mean measured values (ADCscan1=1.529×10(-3)mm(2)/s; ADCscan2=1.507×10(-3)mm(2)/s). Technical and clinical observers demonstrated excellent intra-observer repeatability (ICC>0.9). Clinical observer CoR values were marginally better than technical observer measures (ADCS=0.035×10(-3)mm(2)/s vs. 0.097×10(-3)mm(2)/s; ADCmin=0.09×10(-3)mm(2)/s vs. 0.114×10(-3)mm(2)/s). Inter-reader ICC values were good 0.864 (ADCS) and fair 0.677 (ADCmin). Corresponding CoR values were 0.202×10(-3)mm(2)/s and 0.264×10(-3)mm(2)/s, respectively. Both scanner stability and scan-scan variation have minimal influence on breast ADC measurements, contributing less than 10% error of average measured ADC values. Measurement of ADC values from a small ROI contributes a greater variability in measurements compared with measurement of ADC across the whole visible tumor on one slice. The greatest source of error in follow-up studies is likely to be associated with measures made by multiple observers, and this should be considered where multiple measures are required to assess response to treatment. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Diagnostic value of diffusion weighted MRI and ADC in differential diagnosis of cavernous hemangioma of the liver.

PubMed

Tokgoz, Ozlem; Unlu, Ebru; Unal, Ilker; Serifoglu, Ismail; Oz, Ilker; Aktas, Elif; Caglar, Emrah

2016-03-01

To investigate the use of diffusion weighted magnetic resonance imaging (DWI) and the apparent diffusion coefficient (ADC) values in the diagnosis of hemangioma. The study population consisted of 72 patients with liver masses larger than 1 cm (72 focal lesions). DWI examination with a b value of 600 s/mm2 was carried out for all patients. After DWI examination, an ADC map was created and ADC values were measured for 72 liver masses and normal liver tissue (control group). The average ADC values of normal liver tissue and focal liver lesions, the "cut-off" ADC values, and the diagnostic sensitivity and specificity of the ADC map in diagnosing hemangioma, benign and malignant lesions were researched. Of the 72 liver masses, 51 were benign and 21 were malignant. Benign lesions comprised 38 hemangiomas and 13 simple cysts. Malignant lesions comprised 9 hepatocellular carcinomas, and 12 metastases. The highest ADC values were measured for cysts (3.782±0.53×10(-3) mm(2)/s) and hemangiomas (2.705±0.63×10(-3) mm(2)/s). The average ADC value of hemangiomas was significantly higher than malignant lesions and the normal control group (p<0.001). The average ADC value of cysts were significantly higher when compared to hemangiomas and normal control group (p<0.001). To distinguish hemangiomas from malignant liver lesions, the "cut-off" ADC value of 1.800×10(-3) mm(2)/s had a sensitivity of 97.4% and a specificity of 90.9%. To distinguish hemangioma from normal liver parenchyma the "cut-off" value of 1.858×10(-3) mm(2)/s had a sensitivity of 97.4% and a specificity of 95.7%. To distinguish benign liver lesions from malignant liver lesions the "cut-off" value of 1.800×10(-3) mm(2)/s had a sensitivity of 96.1% and a specificity of 90.0%. DWI and quantitative measurement of ADC values can be used in differential diagnosis of benign and malignant liver lesions and also in the diagnosis and differentiation of hemangiomas. When dynamic examination cannot distinguish cases with vascular metastasis and lesions from hemangioma, DWI and ADC values can be useful in the primary diagnosis and differential diagnosis. The technique does not require contrast material, so it can safely be used in patients with renal failure.

Digital Receiver Phase Meter

NASA Technical Reports Server (NTRS)

Marcin, Martin; Abramovici, Alexander

2008-01-01

The software of a commercially available digital radio receiver has been modified to make the receiver function as a two-channel low-noise phase meter. This phase meter is a prototype in the continuing development of a phase meter for a system in which radiofrequency (RF) signals in the two channels would be outputs of a spaceborne heterodyne laser interferometer for detecting gravitational waves. The frequencies of the signals could include a common Doppler-shift component of as much as 15 MHz. The phase meter is required to measure the relative phases of the signals in the two channels at a sampling rate of 10 Hz at a root power spectral density <5 microcycle/(Hz)1/2 and to be capable of determining the power spectral density of the phase difference over the frequency range from 1 mHz to 1 Hz. Such a phase meter could also be used on Earth to perform similar measurements in laser metrology of moving bodies. To illustrate part of the principle of operation of the phase meter, the figure includes a simplified block diagram of a basic singlechannel digital receiver. The input RF signal is first fed to the input terminal of an analog-to-digital converter (ADC). To prevent aliasing errors in the ADC, the sampling rate must be at least twice the input signal frequency. The sampling rate of the ADC is governed by a sampling clock, which also drives a digital local oscillator (DLO), which is a direct digital frequency synthesizer. The DLO produces samples of sine and cosine signals at a programmed tuning frequency. The sine and cosine samples are mixed with (that is, multiplied by) the samples from the ADC, then low-pass filtered to obtain in-phase (I) and quadrature (Q) signal components. A digital signal processor (DSP) computes the ratio between the Q and I components, computes the phase of the RF signal (relative to that of the DLO signal) as the arctangent of this ratio, and then averages successive such phase values over a time interval specified by the user.

Why prostate tumour delineation based on apparent diffusion coefficient is challenging: an exploration of the tissue microanatomy.

PubMed

Borren, Alie; Moman, Maaike R; Groenendaal, Greetje; Boeken Kruger, Arto E; van Diest, Paul J; van der Groep, Petra; van der Heide, Uulke A; van Vulpen, Marco; Philippens, Marielle E P

2013-11-01

Focal boosting of prostate tumours to improve outcome, requires accurate tumour delineation. For this, the apparent diffusion coefficient (ADC) derived from diffusion-weighted MR imaging (DWI) seems a useful tool. On voxel level, the relationship between ADC and histological presence of tumour is, however, ambiguous. Therefore, in this study the relationship between ADC and histological variables was investigated on voxel level to understand the strengths and limitations of DWI for prostate tumour delineation. Twelve radical prostatectomy patients underwent a pre-operative 3.0T DWI exam and the ADC was calculated. From whole-mount histological sections cell density and glandular area were retrieved for every voxel. The distribution of all variables was described for tumour, peripheral zone (PZ) and central gland (CG) on regional and voxel level. Correlations between variables and differences between regions were calculated. Large heterogeneity of ADC on voxel level was observed within tumours, between tumours and between patients. This heterogeneity was reflected by the distribution of cell density and glandular area. On regional level, tumour was different from PZ having higher cell density (p = 0.007), less glandular area (p = 0.017) and lower ADCs (p = 0.017). ADC was correlated with glandular area (r = 0.402) and tumour volume (r = -0.608), but not with Gleason score. ADC tended to decrease with increasing cell density (r = -0.327, p = 0.073). On voxel level, correlations between ADC and histological variables varied among patients, for cell density ranging from r = -0.439 to r = 0.261 and for glandular area from r = 0.593 to r = 0.207. The variation in ADC can to a certain extent be explained by the variation in cell density and glandular area. The ADC is highly heterogeneous, which reflects the heterogeneity of malignant and benign prostate tissue. This heterogeneity might however obscure small tumours or parts of tumours. Therefore, DWI has to be used in the context of multiparametric MRI.

Effect of intravenous gadolinium-DTPA on diffusion-weighted imaging of brain tumors: a short temporal interval assessment.

PubMed

Li, Xiang; Qu, Jin-Rong; Luo, Jun-Peng; Li, Jing; Zhang, Hong-Kai; Shao, Nan-Nan; Kwok, Keith; Zhang, Shou-Ning; Li, Yan-le; Liu, Cui-Cui; Zee, Chi-Shing; Li, Hai-Liang

2014-09-01

To determine the effect of intravenous administration of gadolinium (Gd) contrast medium (Gd-DTPA) on diffusion-weighted imaging (DWI) for the evaluation of normal brain parenchyma vs. brain tumor following a short temporal interval. Forty-four DWI studies using b values of 0 and 1000 s/mm(2) were performed before, immediately after, 1 min after, 3 min after, and 5 min after the administration of Gd-DTPA on 62 separate lesions including 15 meningioma, 17 glioma and 30 metastatic lesions. The signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR) and apparent diffusion coefficient (ADC) values of the brain tumor lesions and normal brain tissues were measured on pre- and postcontrast images. Statistical analysis using paired t-test between precontrast and postcontrast data were obtained on three brain tumors and normal brain tissue. The SNR and CNR of brain tumors and the SNR of normal brain tissue showed no statistical differences between pre- and postcontrast (P > 0.05). The ADC values on the three cases of brain tumors demonstrated significant initial increase on the immediate time point (P < 0.01) and decrease on following the 1 min time point (P < 0.01) after contrast. Significant decrease of ADC value was still found at 3min and 5min time point in the meningioma group (P < 0.01) with gradual normalization over time. The ADC values of normal brain tissues demonstrated significant initial elevation on the immediately postcontrast DWI sequence (P < 0.01). Contrast medium can cause a slight but statistically significant change on the ADC value within a short temporal interval after the contrast administration. The effect is both time and lesion-type dependent. © 2013 Wiley Periodicals, Inc.

The collagen receptor uPARAP/Endo180 as a novel target for antibody-drug conjugate mediated treatment of mesenchymal and leukemic cancers

PubMed Central

Nielsen, Christoffer Fagernæs; van Putten, Sander Maarten; Lund, Ida Katrine; Melander, Maria Carlsén; Nørregaard, Kirstine Sandal; Jürgensen, Henrik Jessen; Reckzeh, Kristian; Christensen, Kristine Rothaus; Ingvarsen, Signe Ziir; Gårdsvoll, Henrik; Jensen, Kamilla Ellermann; Hamerlik, Petra; Engelholm, Lars Henning; Behrendt, Niels

2017-01-01

A key task in developing the field of personalized cancer therapy is the identification of novel molecular targets that enable treatment of cancers not susceptible to other means of specific therapy. The collagen receptor uPARAP/Endo180 is overexpressed by malignant cells in several non-epithelial cancers, notably including sarcomas, glioblastomas and subsets of acute myeloid leukemia. In contrast, in healthy adult individuals, expression is restricted to minor subsets of mesenchymal cells. Functionally, uPARAP/Endo180 is a rapidly recycling endocytic receptor that delivers its cargo directly into the endosomal-lysosomal system, thus opening a potential route of entry into receptor-positive cells. This combination of specific expression and endocytic function appears well suited for targeting of uPARAP/Endo180-positive cancers by antibody-drug conjugate (ADC) mediated drug delivery. Therefore, we utilized a specific monoclonal antibody against uPARAP/Endo180, raised through immunization of a uPARAP/Endo180 knock-out mouse, which reacts with both the human and the murine receptor, to construct a uPARAP-directed ADC. This antibody was coupled to the highly toxic dolastatin derivative, monomethyl auristatin E, via a cathepsin-labile valine-citrulline linker. With this ADC, we show strong and receptor-dependent cytotoxicity in vitro in uPARAP/Endo180-positive cancer cell lines of sarcoma, glioblastoma and leukemic origin. Furthermore, we demonstrate the potency of the ADC in vivo in a xenograft mouse model with human uPARAP/Endo180-positive leukemic cells, obtaining a complete cure of all tested mice following intravenous ADC treatment with no sign of adverse effects. Our study identifies uPARAP/Endo180 as a promising target for novel therapy against several highly malignant cancer types. PMID:28574834

Diffusion-weighted magnetic resonance imaging in autoimmune pancreatitis.

PubMed

Taniguchi, Takao; Kobayashi, Hisato; Nishikawa, Koji; Iida, Etsushi; Michigami, Yoshihiro; Morimoto, Emiko; Yamashita, Rikiya; Miyagi, Ken; Okamoto, Motozumi

2009-04-01

The aim of this study was to investigate the usefulness of diffusion-weighted magnetic resonance imaging (DWI MRI) for the diagnosis and evaluation of autoimmune pancreatitis (AIP). A total of 4 consecutive patients with AIP, 5 patients with chronic alcoholic pancreatitis (CP), and 13 patients without pancreatic disease (controls) were studied. DWI was performed in the axial plane with spin-echo echo-planar imaging single-shot sequence. Apparent diffusion coefficients (ADCs) were measured in circular regions of interest in the pancreas. In AIP patients, abdominal MRI was performed before, and 2-4 weeks after steroid treatment. Follow-up study was performed chronologically for up to 11 months in two patients. The correlation between ADCs of the pancreas and the immunoglobulin G4 (IgG4) index (serum IgG4 value/serum IgG4 value before steroid treatment) was evaluated. In the AIP patients, DWI of the pancreas showed high signal intensity, and the ADCs of the pancreas (mean +/- SD: 0.97 +/- 0.18 x 10(-3) mm(2)/s) were significantly lower than those in patients with CP (1.45 +/- 0.10 x 10(-3) mm(2)/s) or the controls (1.45 +/- 0.16 x 10(-3) mm(2)/s) (Mann-Whitney U-test, P < 0.05). In one AIP patient with focal swelling of the pancreas head that appeared to be a mass, DWI showed high signal intensity throughout the pancreas, indicating diffuse involvement. The ADCs of the pancreas and IgG4 index were significantly inversely correlated (Spearman's rank correlation coefficient, r (s) = -0.80, P < 0.05). Autoimmune pancreatitis showed high signal intensity on DWI, which improved after steroid treatment. ADCs reflected disease activity. Thus, diffusion-weighted MRI might be useful for diagnosing AIP, determining the affected area, and evaluating the effect of treatment.

Quantitative Analysis of Diffusion-Weighted Imaging for Diagnosis of Puerperal Breast Abscess After Polyacrylamide Hydrogel Augmentation Mammoplasty: Compared with Other Conventional Modalities.

PubMed

Liu, Lihua; Long, Miaomiao; Wang, Junping; Liu, Ning; Ge, Xihong; Hu, Zhandong; Shen, Wen

2015-02-01

Puerperal breast abscess after polyacrylamide hydrogel (PAAG) augmentation mammoplasty can induce breast auto-inflation resulting in serious consequences. Mammography, ultrasound, and conventional MRI are poor at detecting related PAAG abnormality histologically. We evaluated the value of diffusion-weighted imaging (DWI) in the quantitative analysis of puerperal PAAG abscess after augmentation mammoplasty. This was a retrospective study, and a waiver for informed consent was granted. Sixteen puerperal women with breast discomfort underwent conventional breast non-enhanced MRI and axial DWI using a 3T MR scanner. Qualitative analysis of the signal intensity on DWI and conventional sequences was performed. The apparent diffusion coefficient (ADC) values of the affected and contralateral normal PAAG cysts were measured quantitatively. Paired t test was used to evaluate whether there was significant difference. Both affected and normal PAAG cysts showed equal signal intensity on conventional T1WI and fat saturation T2WI, which were not helpful in detecting puerperal PAAG abscess. However, the affected PAAG cysts had a significantly decreased ADC value of 1.477 ± 0.332 × 10(-3)mm(2)/s and showed obvious hypo-intensity on the ADC map and increased signal intensity on DWI compared with the ADC value of 2.775 ± 0.233 × 10(-3)mm(2)/s of the contralateral normal PAAG cysts. DWI and quantitative measurement of ADC values are of great value for the diagnosis of puerperal PAAG abscess. Standardized MRI should be suggested to these puerperal women with breast discomfort or just for the purpose of check up. DWI should be selected as the essential MRI sequence.

Metrics and textural features of MRI diffusion to improve classification of pediatric posterior fossa tumors.

PubMed

Rodriguez Gutierrez, D; Awwad, A; Meijer, L; Manita, M; Jaspan, T; Dineen, R A; Grundy, R G; Auer, D P

2014-05-01

Qualitative radiologic MR imaging review affords limited differentiation among types of pediatric posterior fossa brain tumors and cannot detect histologic or molecular subtypes, which could help to stratify treatment. This study aimed to improve current posterior fossa discrimination of histologic tumor type by using support vector machine classifiers on quantitative MR imaging features. This retrospective study included preoperative MRI in 40 children with posterior fossa tumors (17 medulloblastomas, 16 pilocytic astrocytomas, and 7 ependymomas). Shape, histogram, and textural features were computed from contrast-enhanced T2WI and T1WI and diffusivity (ADC) maps. Combinations of features were used to train tumor-type-specific classifiers for medulloblastoma, pilocytic astrocytoma, and ependymoma types in separation and as a joint posterior fossa classifier. A tumor-subtype classifier was also produced for classic medulloblastoma. The performance of different classifiers was assessed and compared by using randomly selected subsets of training and test data. ADC histogram features (25th and 75th percentiles and skewness) yielded the best classification of tumor type (on average >95.8% of medulloblastomas, >96.9% of pilocytic astrocytomas, and >94.3% of ependymomas by using 8 training samples). The resulting joint posterior fossa classifier correctly assigned >91.4% of the posterior fossa tumors. For subtype classification, 89.4% of classic medulloblastomas were correctly classified on the basis of ADC texture features extracted from the Gray-Level Co-Occurence Matrix. Support vector machine-based classifiers using ADC histogram features yielded very good discrimination among pediatric posterior fossa tumor types, and ADC textural features show promise for further subtype discrimination. These findings suggest an added diagnostic value of quantitative feature analysis of diffusion MR imaging in pediatric neuro-oncology. © 2014 by American Journal of Neuroradiology.

Apparent diffusion coefficient of breast cancer and normal fibroglandular tissue in diffusion-weighted imaging: the effects of menstrual cycle and menopausal status.

PubMed

Kim, Jin You; Suh, Hie Bum; Kang, Hyun Jung; Shin, Jong Ki; Choo, Ki Seok; Nam, Kyung Jin; Lee, Seok Won; Jung, Young Lae; Bae, Young Tae

2016-05-01

The purpose of this study was to investigate prospectively whether the apparent diffusion coefficients (ADCs) of both breast cancer and normal fibroglandular tissue vary with the menstrual cycle and menopausal status. Institutional review board approval was obtained, and informed consent was obtained from each participant. Fifty-seven women (29 premenopausal, 28 postmenopausal) with newly diagnosed breast cancer underwent diffusion-weighted imaging twice (interval 12-20 days) before surgery. Two radiologists independently measured ADC of breast cancer and normal contralateral breast tissue, and we quantified the differences according to the phases of menstrual cycle and menopausal status. With normal fibroglandular tissue, ADC was significantly lower in postmenopausal than in premenopausal women (P = 0.035). In premenopausal women, ADC did not differ significantly between proliferative and secretory phases in either breast cancer or normal fibroglandular tissue (P = 0.969 and P = 0.519, respectively). In postmenopausal women, no significant differences were found between ADCs measured at different time intervals in either breast cancer or normal fibroglandular tissue (P = 0.948 and P = 0.961, respectively). The within-subject variability of the ADC measurements was quantified using the coefficient of variation (CV) and was small: the mean CVs of tumor ADC were 2.90 % (premenopausal) and 3.43 % (postmenopausal), and those of fibroglandular tissue ADC were 4.37 % (premenopausal) and 2.55 % (postmenopausal). Both intra- and interobserver agreements were excellent for ADC measurements, with intraclass correlation coefficients in the range of 0.834-0.974. In conclusion, the measured ADCs of breast cancer and normal fibroglandular tissue were not affected significantly by menstrual cycle, and the measurements were highly reproducible both within and between observers.

Data-Driven prioritisation of antibody-drug conjugate targets in head and neck squamous cell carcinoma.

PubMed

Hanemaaijer, Saskia H; van Gijn, Stephanie E; Oosting, Sjoukje F; Plaat, Boudewijn E C; Moek, Kirsten L; Schuuring, Ed M; van der Laan, Bernard F A M; Roodenburg, Jan L N; van Vugt, Marcel A T M; van der Vegt, Bert; Fehrmann, Rudolf S N

2018-05-01

For patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) palliative treatment options that improve overall survival are limited. The prognosis in this group remains poor and there is an unmet need for new therapeutic options. An emerging class of therapeutics, targeting tumor-specific antigens, are antibodies bound to a cytotoxic agent, known as antibody-drug conjugates (ADCs). The aim of this study was to prioritize ADC targets in HNSCC. With a systematic search, we identified 55 different ADC targets currently targeted by registered ADCs and ADCs under clinical evaluation. For these 55 ADC targets, protein overexpression was predicted in a dataset containing 344 HNSCC mRNA expression profiles by using a method called functional genomic mRNA profiling. The ADC target with the highest predicted overexpression was validated by performing immunohistochemistry (IHC) on an independent tissue microarray containing 414 HNSCC tumors. The predicted top 5 overexpressed ADC targets in HNSCC were: glycoprotein nmb (GPNMB), SLIT and NTRK-like family member 6, epidermal growth factor receptor, CD74 and CD44. IHC validation showed combined cytoplasmic and membranous GPNMB protein expression in 92.0% of the cases. Strong expression was seen in 65.9% of the cases. In addition, 86.5% and 67.7% of cases showed ≥5% and >25% GPNMB positive tumor cells, respectively. This study provides a data-driven prioritization of ADCs targets that will facilitate clinicians and drug developers in deciding which ADC should be taken for further clinical evaluation in HNSCC. This might help to improve disease outcome of HNSCC patients. Copyright © 2018 Elsevier Ltd. All rights reserved.

Drug-conjugated antibodies for the treatment of cancer

PubMed Central

Lambert, John M

2013-01-01

Despite considerable effort, application of monoclonal antibody technology has had only modest success in improving treatment outcomes in patients with solid tumours. Enhancing the cancer cell-killing activity of antibodies through conjugation to highly potent cytotoxic ‘payloads’ to create antibody–drug conjuates (ADCs) offers a strategy for developing anti-cancer drugs of great promise. Early ADCs exhibited side-effect profiles similar to those of ‘classical’ chemotherapeutic agents and their performance in clinical trials in cancer patients was generally poor. However, the recent clinical development of ADCs that have highly potent tubulin-acting agents as their payloads have profoundly changed the outlook for ADC technology. Twenty-five such ADCs are in clinical development and one, brentuximab vedotin, was approved by the FDA in August, 2011, for the treatment of patients with Hodgkin's lymphoma and patients with anaplastic large cell lymphoma, based on a high rate of durable responses in single arm phase II clinical trials. More recently, a second ADC, trastuzumab emtansine, has shown excellent anti-tumour activity with the presentation of results of a 991-patient randomized phase III trial in patients with HER2-positive metastatic breast cancer. Treatment with this ADC (single agent) resulted in a significantly improved progression-free survival of 9.6 months compared with 6.4 months for lapatinib plus capecitabine in the comparator arm and significantly prolonged overall survival. Besides demonstrating excellent efficacy, these ADCs were remarkably well tolerated. Thus these, and other ADCs in development, promise to achieve the long sought goal of ADC technology, that is, of having compounds with high anti-tumour activity at doses where adverse effects are generally mild. PMID:23173552

Zn2+ Uptake in Streptococcus pyogenes: Characterization of adcA and lmb Null Mutants.

PubMed

Tedde, Vittorio; Rosini, Roberto; Galeotti, Cesira L

2016-01-01

An effective regulation of metal ion homeostasis is essential for the growth of microorganisms in any environment and in pathogenic bacteria is strongly associated with their ability to invade and colonise their hosts. To gain a better insight into zinc acquisition in Group A Streptococcus (GAS) we characterized null deletion mutants of the adcA and lmb genes of Streptococcus pyogenes strain MGAS5005 encoding the orthologues of AdcA and AdcAII, the two surface lipoproteins with partly redundant roles in zinc homeostasis in Streptococcus pneumoniae. Null adcA and lmb mutants were analysed for their capability to grow in zinc-depleted conditions and were found to be more susceptible to zinc starvation, a phenotype that could be rescued by the addition of Zn2+ ions to the growth medium. Expression of AdcA, Lmb and HtpA, the polyhistidine triad protein encoded by the gene adjacent to lmb, during growth under conditions of limited zinc availability was examined by Western blot analysis in wild type and null mutant strains. In the wild type strain, AdcA was always present with little variation in expression levels between conditions of excess or limited zinc availability. In contrast, Lmb and HtpA were expressed at detectable levels only during growth in the presence of low zinc concentrations or in the null adcA mutant, when expression of lmb is required to compensate for the lack of adcA expression. In the latter case, Lmb and HtpA were overexpressed by several fold, thus indicating that also in GAS AdcA is a zinc-specific importer and, although it shares this function with Lmb, the two substrate-binding proteins do not show fully overlapping roles in zinc homeostasis.

Cancer in HIV-infected Persons from the Caribbean, Central and South America

PubMed Central

Fink, Valeria I.; Shepherd, Bryan E.; Cesar, Carina; Krolewiecki, Alejandro; Wehbe, Firas; Cortés, Claudia P.; Crabtree-Ramírez, Brenda; Padgett, Denis; Shafaee, Maryam; Schechter, Mauro; Gotuzzo, Eduardo; Bacon, Melanie; McGowan, Catherine; Cahn, Pedro; Masys, Daniel

2011-01-01

Background HIV infected individuals have heightened cancer risk. With the advent of HAART, the frequency of some AIDS defining cancers (ADC) has decreased while certain non-AIDS defining cancers (NADC) are becoming more frequent. Cancers among HIV-infected individuals in Latin American and the Caribbean have not yet been carefully studied. Methods Cancer cases among the Caribbean, Central and South American network for HIV Research (CCASAnet) cohort were identified reviewing clinical records and preexisting databases. Results There were 406 cancers reported: 331 ADC (224 Kaposi´s sarcomas and 98 non Hodgkin lymphomas). Most frequent NADC (n=75) were Hodgkin lymphoma and skin cancers. Seventy-three percent of NADC and 45% of ADC were diagnosed >1 year after HIV diagnosis. 56% of ADC occurred before HAART start. Median time from HAART start until cancer diagnosis was 2.5 years for NADC and 0.5 years for ADC (p=<0.001). Within 3372 HAART starters, 158 were diagnosed with 165 cancers (82.4% ADC); 85 cases were previous to or concomitant with HAART initiation. Incidence of cancer after HAART initiation in 8080 person-years of follow-up was 7.2 per 1000 person-years (95%CI= 5.5–9.3) for ADC and 2.7 (95%CI= 1.8–4.1) for NADC; incidence was higher in the first two months, particularly for ADC (47.6). A pre-HAART ADC was a predictor of mortality after adjusting for age, sex, and CD4 at HAART initiation. Conclusions ADC were the most frequent cancers in this region and were often diagnosed close to HIV diagnosis and HAART start. Incidence of cancer was highest around HAART initiation. PMID:21239992

PI-RADS v2 and ADC values: is there room for improvement?

PubMed

Jordan, Eric J; Fiske, Charles; Zagoria, Ronald; Westphalen, Antonio C

2018-03-17

To determine the diagnostic accuracy of ADC values in combination with PI-RADS v2 for the diagnosis of clinically significant prostate cancer (CS-PCa) compared to PI-RADS v2 alone. This retrospective study included 155 men whom underwent 3-Tesla prostate MRI and subsequent MR/US fusion biopsies at a single non-academic center from 11/2014 to 3/2016. All scans were performed with a surface coil and included T2, diffusion-weighted, and dynamic contrast-enhanced sequences. Suspicious findings were classified using Prostate Imaging Reporting and Data System (PI-RADS) v2 and targeted using MR/US fusion biopsies. Mixed-effect logistic regression analyses were used to determine the ability of PIRADS v2 alone and combined with ADC values to predict CS-PCa. As ADC categories are more practical in clinical situations than numeric values, an additional model with ADC categories of ≤ 800 and > 800 was performed. A total of 243 suspicious lesions were included, 69 of which were CS-PCa, 34 were Gleason score 3+3 PCa, and 140 were negative. The overall PIRADS v2 score, ADC values, and ADC categories are independent statistically significant predictors of CS-PCa (p < 0.001). However, the area under the ROC of PIRADS v2 alone and PIRADS v2 with ADC categories are significantly different in both peripheral and transition zone lesions (p = 0.026 and p = 0.03, respectively) Further analysis of the ROC curves also shows that the main benefit of utilizing ADC values or categories is better discrimination of PI-RADS v2 4 lesions. ADC values and categories help to diagnose CS-PCa when lesions are assigned a PI-RADS v2 score of 4.

Pre-operative assessment of residual disease in locally advanced breast cancer patients: A sequential study by quantitative diffusion weighted MRI as a function of therapy.

PubMed

Agarwal, Khushbu; Sharma, Uma; Sah, Rani G; Mathur, Sandeep; Hari, Smriti; Seenu, Vurthaluru; Parshad, Rajinder; Jagannathan, Naranamangalam R

2017-10-01

The potential of diffusion weighted imaging (DWI) in assessing pathologic response and surgical margins in locally advanced breast cancer patients (n=38) undergoing neoadjuvant chemotherapy was investigated. DWI was performed at pre-therapy (Tp0), after I (Tp1) and III (Tp3) NACT at 1.5T. Apparent diffusion coefficient (ADC) of whole tumor (ADC WT ), solid tumor (ADC ST ), intra-tumoral necrosis (ADC Nec ) was determined. Further, ADC of 6 consecutive shells (5mm thickness each) including tumor margin to outside tumor margins (OM1 to OM5) was calculated and the data analyzed to define surgical margins. Of 38 patients, 6 were pathological complete responders (pCR), 19 partial responders (pPR) and 13 were non-responders (pNR). Significant increase was observed in ADC ST and ADC WT in pCR and pPR following therapy. Pre-therapy ADC was significantly lower in pCR compared to pPR and pNR indicating the heterogeneous nature of tumor which may affect drug perfusion and consequently the response. ADC of outside margins (OM1, OM2, and OM3) was significantly different among pCR, pPR and pNR at Tp3 which may serve as response predictive parameter. Further, at Tp3, ADC of outside margins (OM1, OM2, and OM3) was significantly lower compared to that seen at Tp0 in pCR, indicating the presence of residual disease in these shells. Pre-surgery information may serve as a guide to define cancer free margins and the extent of residual disease which may be useful in planning breast conservation surgery. Copyright © 2017 Elsevier Inc. All rights reserved.

Alterations in apparent diffusion coefficient values of the kidney during the cardiac cycle: Evaluation with ECG-triggered diffusion-weighted MR imaging.

PubMed

Ito, Katsuyoshi; Hayashida, Minoru; Kanki, Akihiko; Yamamoto, Akira; Tamada, Tsutomu; Yoshida, Koji; Tanabe, Masahiro

2018-05-17

To evaluate dynamic changes in apparent diffusion coefficient (ADC) values of the kidney at different time points during the cardiac cycle using electrocardiographic (ECG)-triggered diffusion-weighted MR imaging in normal subjects, and to elucidate the differences in ADC values between the right and left kidneys during a cardiac cycle. The study was approved by our institutional review board and informed consent was obtained from subjects. Twenty healthy volunteers who underwent ECG-triggered diffusion-weighted MR imaging of the kidney were included. The differences in ADC values of each kidney during different cardiac phases were compared. Additionally, the differences in maximum and minimum ADC values between the right and left kidney were also evaluated. ADC values in the right and left kidney changed significantly during the cardiac cycle (P < 0.00001). Maximum and minimum ADC values during the cardiac cycle of the left kidney were significantly higher (P = 0.026 and 0.017, respectively) than those of the right kidney. Maximum ADC value in the left kidney had a significantly strong positive correlation with the left renal vein ratio (r = 0.83, P < 0.00001). In the right kidney, maximum ADC showed a weakly positive correlation with the diameter of the right renal vein (r = 0.45, P = 0.048). ADC values of the kidney obtained using ECG-triggered diffusion-weighted MR imaging change significantly during the cardiac cycle. Maximum (systolic) ADC during the cardiac cycle of the left kidney was significantly higher than that of the right kidney, probably due to the anatomical difference in the renal vein. Copyright © 2018 Elsevier Inc. All rights reserved.

Piriformis muscle syndrome with assessment of sciatic nerve using diffusion tensor imaging and tractography: a case report.

PubMed

Wada, Keizo; Goto, Tomohiro; Takasago, Tomoya; Hamada, Daisuke; Sairyo, Koichi

2017-10-01

Piriformis muscle syndrome (PMS) is difficult to diagnose by objective evaluation of sciatic nerve injury. Here we report a case of PMS diagnosed by diffusion tensor imaging (DTI) and tractography of the sciatic nerve, which can assess and visualize the extent of nerve injury. The patient was a 53-year-old man with a 2-year history of continuous pain and numbness in the left leg. His symptoms worsened when sitting. Physical examination, including sensorimotor neurologic tests, the deep tendon reflex test, and the straight leg raise test, revealed no specific findings. The hip flexion adduction and internal rotation test and resisted contraction maneuvers for the piriformis muscle were positive. There were no abnormal findings on magnetic resonance imaging (MRI) of the lumbar spine. The transverse diameter of piriformis muscle was slightly thicker in affected side on MRI of the pelvis. A single DTI sequence was performed during MRI of the pelvis. Fractional anisotropy (FA) and the apparent diffusion coefficient (ADC) of the sciatic nerve were quantified at three levels using the fiber-tracking method. FA values were significantly lower and ADC values were significantly higher distal to the piriformis muscle. We performed endoscopic-assisted resection of the piriformis tendon. Intraoperatively, the motor-evoked potentials in the left gastrocnemius were improved by resection of the piriformis tendon. The patient's symptoms improved immediately after surgery. There was no significant difference in FA or ADC at any level between the affected side and the unaffected side 3 months postoperatively. MRI-DTI may aid the diagnosis of PMS.

Data acquisition electronics for gamma ray emission tomography using width-modulated leading-edge discriminators

NASA Astrophysics Data System (ADS)

Lage, E.; Tapias, G.; Villena, J.; Desco, M.; Vaquero, J. J.

2010-08-01

We present a new high-performance and low-cost approach for implementing radiation detection acquisition systems. The basic elements used are charge-integrating ADCs and a set of components encapsulated in an HDL (hardware definition language) library which makes it possible to implement several acquisition tasks such as time pickoff and coincidence detection using a new and simple trigger technique that we name WMLET (width-modulated leading-edge timing). As proof of concept, a 32-channel hybrid PET/SPECT acquisition system based on these elements was developed and tested. This demonstrator consists of a master module responsible for the generation and distribution of trigger signals, 2 × 16-channel ADC cards (12-bit resolution) for data digitization and a 32-bit digital I/O PCI card for handling data transmission to a personal computer. System characteristics such as linearity, maximum transmission rates or timing resolution in coincidence mode were evaluated with test and real detector signals. Imaging capabilities of the prototype were also evaluated using different detector configurations. The performance tests showed that this implementation is able to handle data rates in excess of 600k events s-1 when acquiring simultaneously 32 channels (96-byte events). ADC channel linearity is >98.5% in energy quantification. Time resolution in PET mode for the tested configurations ranges from 3.64 ns FWHM to 7.88 ns FWHM when signals from LYSO-based detectors are used. The measured energy resolution matched the expected values for the detectors evaluated and single elements of crystal matrices can be neatly separated in the acquired flood histograms.

Data acquisition electronics for gamma ray emission tomography using width-modulated leading-edge discriminators.

PubMed

Lage, E; Tapias, G; Villena, J; Desco, M; Vaquero, J J

2010-08-07

We present a new high-performance and low-cost approach for implementing radiation detection acquisition systems. The basic elements used are charge-integrating ADCs and a set of components encapsulated in an HDL (hardware definition language) library which makes it possible to implement several acquisition tasks such as time pickoff and coincidence detection using a new and simple trigger technique that we name WMLET (width-modulated leading-edge timing). As proof of concept, a 32-channel hybrid PET/SPECT acquisition system based on these elements was developed and tested. This demonstrator consists of a master module responsible for the generation and distribution of trigger signals, 2 x 16-channel ADC cards (12-bit resolution) for data digitization and a 32-bit digital I/O PCI card for handling data transmission to a personal computer. System characteristics such as linearity, maximum transmission rates or timing resolution in coincidence mode were evaluated with test and real detector signals. Imaging capabilities of the prototype were also evaluated using different detector configurations. The performance tests showed that this implementation is able to handle data rates in excess of 600k events s(-1) when acquiring simultaneously 32 channels (96-byte events). ADC channel linearity is >98.5% in energy quantification. Time resolution in PET mode for the tested configurations ranges from 3.64 ns FWHM to 7.88 ns FWHM when signals from LYSO-based detectors are used. The measured energy resolution matched the expected values for the detectors evaluated and single elements of crystal matrices can be neatly separated in the acquired flood histograms.

An 11-bit 200 MS/s subrange SAR ADC with low-cost integrated reference buffer

NASA Astrophysics Data System (ADS)

He, Xiuju; Gu, Xian; Li, Weitao; Jiang, Hanjun; Li, Fule; Wang, Zhihua

2017-10-01

This paper presents an 11-bit 200 MS/s subrange SAR ADC with an integrated reference buffer in 65 nm CMOS. The proposed ADC employs a 3.5-bit flash ADC for coarse conversion, and a compact timing scheme at the flash/SAR boundary to speed up the conversion. The flash decision is used to control charge compensating for the reference voltage to reduce its input-dependent fluctuation. Measurement results show that the fabricated ADC has achieved significant improvement by applying the reference charge compensation. In addition, the ADC achieves a maximum signal-to-noise-and-distortion ratio of 59.3 dB at 200 MS/s. It consumes 3.91 mW from a 1.2 V supply, including the reference buffer. Project supported by the Zhongxing Telecommunication Equipment Corporation and Beijing Microelectronics Technology Institute.

Metal Organic Framework Micro/Nanopillars of Cu(BTC)·3H₂O and Zn(ADC)·DMSO.

PubMed

Kojtari, Arben; Ji, Hai-Feng

2015-04-09

In this work, we report the optical and thermal properties of Cu(BTC)·3H₂O (BTC = 1,3,5-benzenetricarboxylic acid) and Zn(ADC)·DMSO (ADC = 9,10- anthracenedicarboxylic acid, DMSO = dimethyl sulfoxide) metal-organic frameworks (MOFs) micro/nanopillars. The morphologies of MOFs on surfaces are most in the form of micro/nanopillars that were vertically oriented on the surface. The size and morphology of the pillars depend on the evaporation time, concentration, solvent, substrate, and starting volume of solutions. The crystal structures of the nanopillars and micropillars are the same, confirmed by powder XRD. Zn(ADC)·DMSO pillars have a strong blue fluorescence. Most of ADC in the pillars are in the form of monomers, which is different from ADC in the solid powder.

Characterization of arginine decarboxylase from Dianthus caryophyllus.

PubMed

Ha, Byung Hak; Cho, Ki Joon; Choi, Yu Jin; Park, Ky Young; Kim, Kyung Hyun

2004-04-01

Arginine decarboxylase (ADC, EC 4.1.1.9) is a key enzyme in the biosynthesis of polyamines in higher plants, whereas ornithine decarboxylase represents the sole pathway of polyamine biosynthesis in animals. Previously, we characterized a genomic clone from Dianthus caryophyllus, in which the deduced polypeptide of ADC was 725 amino acids with a molecular mass of 78 kDa. In the present study, the ADC gene was subcloned into the pGEX4T1 expression vector in combination with glutathione S-transferase (GST). The fusion protein GST-ADC was water-soluble and thus was purified by sequential GSTrap-arginine affinity chromatography. A thrombin-mediated on-column cleavage reaction was employed to release free ADC from GST. Hiload superdex gel filtration FPLC was then used to obtain a highly purified ADC. The identity of the ADC was confirmed by immunoblot analysis, and its specific activity with respect to (14)C-arginine decarboxylation reaction was determined to be 0.9 CO(2) pkat mg(-1) protein. K(m) and V(max) of the reaction between ADC and the substrate were 0.077 +/- 0.001 mM and 6.0 +/- 0.6 pkat mg(-1) protein, respectively. ADC activity was reduced by 70% in the presence of 0.1 mM Cu(2+) or CO(2+), but was only marginally affected by Mg(2+), or Ca(2+) at the same concentration. Moreover, spermine at 1 mM significantly reduced its activity by 30%.

Diagnostic performance of conventional MRI parameters and apparent diffusion coefficient values in differentiating between benign and malignant soft-tissue tumours.

PubMed

Song, Y; Yoon, Y C; Chong, Y; Seo, S W; Choi, Y-L; Sohn, I; Kim, M-J

2017-08-01

To compare the abilities of conventional magnetic resonance imaging (MRI) and apparent diffusion coefficient (ADC) in differentiating between benign and malignant soft-tissue tumours (STT). A total of 123 patients with STT who underwent 3 T MRI, including diffusion-weighted imaging (DWI), were retrospectively analysed using variate conventional MRI parameters, ADC mean and ADC min . For the all-STT group, the correlation between the malignant STT conventional MRI parameters, except deep compartment involvement, compared to those of benign STT were statistically significant with univariate analysis. Maximum diameter of the tumour (p=0.001; odds ratio [OR], 8.97) and ADC mean (p=0.020; OR, 4.30) were independent factors with multivariate analysis. For the non-myxoid non-haemosiderin STT group, signal heterogeneity on axial T1-weighted imaging (T1WI; p=0.017), ADC mean , and ADC min (p=0.001, p=0.001), showed significant differences with univariate analysis between malignancy and benignity. Signal heterogeneity in axial T1WI (p=0.025; OR, 12.64) and ADC mean (p=0.004; OR, 33.15) were independent factors with multivariate analysis. ADC values as well as conventional MRI parameters were useful in differentiating between benign and malignant STT. The ADC mean was the most powerful diagnostic parameter in non-myxoid non-haemosiderin STT. Copyright © 2017 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Correlation between electrical conductivity and apparent diffusion coefficient in breast cancer: effect of necrosis on magnetic resonance imaging.

PubMed

Kim, Soo-Yeon; Shin, Jaewook; Kim, Dong-Hyun; Kim, Eun-Kyung; Moon, Hee Jung; Yoon, Jung Hyun; You, Jai Kyung; Kim, Min Jung

2018-03-06

To investigate the correlation between conductivity and ADC in invasive ductal carcinoma according to the presence of necrosis on MRI. Eighty-one women with invasive ductal carcinoma ≥1 cm on T2-weighted fast spin echo sequence of preoperative MRI were included. Phase-based MR electric properties tomography was used to reconstruct conductivity. Mean ADC was measured. Necrosis was defined as an area with very high T2 signal intensity. The relationship between conductivity and ADC was examined using Spearman's correlation coefficient (r). Multiple linear regression analysis was performed to identify factors associated with conductivity or ADC. In the total group, conductivity showed negative correlation with ADC (r = -0.357, p = 0.001). This correlation was maintained in the subgroup without necrosis (n = 53, r = -0.455, p = 0.001), but not in the subgroup with necrosis (n = 28, r = -0.080, p = 0.687). The correlation between the two parameters was different according to necrosis (r = -0.455 vs -0.080, p = 0.047). HER2 enriched subtype was independently associated with conductivity (p = 0.029). Necrosis on MRI was independently associated with ADC (p = 0.027). Conductivity shows negative correlation with ADC that is abolished by the presence of necrosis on MRI. • Electric conductivity showed negative correlation with ADC • However, the correlation was abolished by the presence of necrosis on MRI • HER2-enriched subtype was independently associated with conductivity • Necrosis on MRI was independently associated with ADC.

Evaluation of extra- and intracellular apparent diffusion coefficient of sodium in rat skeletal muscle: effects of prolonged ischemia.

PubMed

Babsky, Andriy M; Topper, Stephen; Zhang, Hong; Gao, Yong; James, Judy R; Hekmatyar, Shahryar K; Bansal, Navin

2008-03-01

The mechanism of water and sodium apparent diffusion coefficient (ADC) changes in rat skeletal muscle during global ischemia was examined by in vivo 1H and 23Na magnetic resonance spectroscopy (MRS). The ADCs of Na+ and water are expected to have similar characteristics because sodium is present as an aqua-cation in tissue. The shift reagent, TmDOTP5(-), was used to separate intra- and extracellular sodium (Na+i and Na+e, respectively) signals. Water, total tissue sodium (Na+t), Na+i, and Na+e ADCs were measured before and 1, 2, 3, and 4 hr after ischemia. Contrary to the general perception, Na+i and Na+e ADCs were identical before ischemia. Thus, ischemia-induced changes in Na+e ADC cannot be explained by a simple change in the size of relative intracellular or extracellular space. Na+t and Na+e ADCs decreased after 2-4 hr of ischemia, while water and Na+i ADC remained unchanged. The correlation between Na+t and Na+e ADCs was observed because of high Na+e concentration. Similarly, the correlation between water and Na+i ADCs was observed because cells occupy 80% of the tissue space in the skeletal muscle. Ischemia also caused an increase in the Na+i and an equal decrease in Na+e signal intensity due to cessation of Na+/K+-ATPase function. (c) 2008 Wiley-Liss, Inc.

Design and development of digital seismic amplifier recorder

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

Samsidar, Siti Alaa; Afuar, Waldy; Handayani, Gunawan, E-mail: gunawanhandayani@gmail.com

2015-04-16

A digital seismic recording is a recording technique of seismic data in digital systems. This method is more convenient because it is more accurate than other methods of seismic recorders. To improve the quality of the results of seismic measurements, the signal needs to be amplified to obtain better subsurface images. The purpose of this study is to improve the accuracy of measurement by amplifying the input signal. We use seismic sensors/geophones with a frequency of 4.5 Hz. The signal is amplified by means of 12 units of non-inverting amplifier. The non-inverting amplifier using IC 741 with the resistor values 1KΩmore » and 1MΩ. The amplification results were 1,000 times. The results of signal amplification converted into digital by using the Analog Digital Converter (ADC). Quantitative analysis in this study was performed using the software Lab VIEW 8.6. The Lab VIEW 8.6 program was used to control the ADC. The results of qualitative analysis showed that the seismic conditioning can produce a large output, so that the data obtained is better than conventional data. This application can be used for geophysical methods that have low input voltage such as microtremor application.« less

Prognostic Value of the Apparent Diffusion Coefficient in Newborns with Hypoxic-Ischaemic Encephalopathy Treated with Therapeutic Hypothermia.

PubMed

Heursen, Eva-Marie; Zuazo Ojeda, Amaya; Benavente Fernández, Isabel; Jimenez Gómez, Gema; Campuzano Fernández-Colima, Rosalía; Paz-Expósito, José; Lubián López, Simón Pedro

2017-01-01

Apparent diffusion coefficient (ADC) quantification has been proven to be of prognostic value in term newborns with hypoxic-ischaemic encephalopathy (HIE) who were treated under normothermia. To evaluate the prognostic value of ADC in standardized brain regions in neonates with HIE who were treated with therapeutic hypothermia (TH). This prospective cohort study included 54 term newborns who were admitted with HIE and treated with TH. All magnetic resonance imaging examinations were performed between days 4 and 6 of life, and ADC values were measured in 13 standardized regions of the brain. At 2 years of age we explored whether ADC values were related to composite outcomes (death or survival with abnormal neurodevelopment). The severity of HIE is inversely related to ADC values in different brain regions. We found that lower ADC values in the posterior limb of the internal capsule (PLIC), the thalami, the semioval centre, and frontal and parietal white matter were related to adverse outcomes. ADC values in the PLIC and thalami are good predictors of adverse outcomes (AUC 0.86 and 0.76). Low ADC values in the PLIC, thalamus, semioval centre, and frontal and parietal white matter in full-term infants with HIE treated with TH were associated with a poor outcome. © 2017 S. Karger AG, Basel.

A two-step A/D conversion and column self-calibration technique for low noise CMOS image sensors.

PubMed

Bae, Jaeyoung; Kim, Daeyun; Ham, Seokheon; Chae, Youngcheol; Song, Minkyu

2014-07-04

In this paper, a 120 frames per second (fps) low noise CMOS Image Sensor (CIS) based on a Two-Step Single Slope ADC (TS SS ADC) and column self-calibration technique is proposed. The TS SS ADC is suitable for high speed video systems because its conversion speed is much faster (by more than 10 times) than that of the Single Slope ADC (SS ADC). However, there exist some mismatching errors between the coarse block and the fine block due to the 2-step operation of the TS SS ADC. In general, this makes it difficult to implement the TS SS ADC beyond a 10-bit resolution. In order to improve such errors, a new 4-input comparator is discussed and a high resolution TS SS ADC is proposed. Further, a feedback circuit that enables column self-calibration to reduce the Fixed Pattern Noise (FPN) is also described. The proposed chip has been fabricated with 0.13 μm Samsung CIS technology and the chip satisfies the VGA resolution. The pixel is based on the 4-TR Active Pixel Sensor (APS). The high frame rate of 120 fps is achieved at the VGA resolution. The measured FPN is 0.38 LSB, and measured dynamic range is about 64.6 dB.

A low-power small-area ADC array for IRFPA readout

NASA Astrophysics Data System (ADS)

Zhong, Shengyou; Yao, Libin

2013-09-01

The readout integrated circuit (ROIC) is a bridge between the infrared focal plane array (IRFPA) and image processing circuit in an infrared imaging system. The ROIC is the first part of signal processing circuit and connected to detectors directly, so its performance will greatly affect the detector or even the whole imaging system performance. With the development of CMOS technologies, it's possible to digitalize the signal inside the ROIC and develop the digital ROIC. Digital ROIC can reduce complexity of the whole system and improve the system reliability. More importantly, it can accommodate variety of digital signal processing techniques which the traditional analog ROIC cannot achieve. The analog to digital converter (ADC) is the most important building block in the digital ROIC. The requirements for ADCs inside the ROIC are low power, high dynamic range and small area. In this paper we propose an RC hybrid Successive Approximation Register (SAR) ADC as the column ADC for digital ROIC. In our proposed ADC structure, a resistor ladder is used to generate several voltages. The proposed RC hybrid structure not only reduces the area of capacitor array but also releases requirement for capacitor array matching. Theory analysis and simulation show RC hybrid SAR ADC is suitable for ADC array applications

Diffusion weighted imaging reflects variable cellularity and stromal density present in breast fibroadenomas

PubMed Central

Parsian, Sana; Giannakopoulos, Nadia V.; Rahbar, Habib; Rendi, Mara H.; Chai, Xiaoyu

2016-01-01

OBJECTIVE To determine the underlying histopathologic features influencing apparent diffusion coefficient (ADC) values of breast fibroadenomas. MATERIALS AND METHODS Biopsy proven fibroadenomas (n=26) initially identified as suspicious on breast MRI were retrospectively evaluated. Histopathological assessments of lesion cellularity and stromal type were compared with ADC measures on diffusion-weighted MRI. RESULTS Presence of epithelial hyperplasia (increased cellularity) and dense collagenous stroma were both significantly associated with lower lesion ADC values (p=0.02 and 0.004, respectively. CONCLUSION Variations in epithelial cellularity and stromal type influence breast lesion ADC values and may explain the wide range of ADC measures observed in benign fibroadenomas. PMID:27379441

A 25μm pitch LWIR focal plane array with pixel-level 15-bit ADC providing high well capacity and targeting 2mK NETD

NASA Astrophysics Data System (ADS)

Guellec, Fabrice; Peizerat, Arnaud; Tchagaspanian, Michael; de Borniol, Eric; Bisotto, Sylvette; Mollard, Laurent; Castelein, Pierre; Zanatta, Jean-Paul; Maillart, Patrick; Zecri, Michel; Peyrard, Jean-Christophe

2010-04-01

CEA Leti has recently developed a new readout IC (ROIC) with pixel-level ADC for cooled infrared focal plane arrays (FPAs). It operates at 50Hz frame rate in a snapshot Integrate-While-Read (IWR) mode. It targets applications that provide a large amount of integrated charge thanks to a long integration time. The pixel-level analog-to-digital conversion is based on charge packets counting. This technique offers a large well capacity that paves the way for a breakthrough in NETD performances. The 15 bits ADC resolution preserves the excellent detector SNR at full well (3Ge-). These characteristics are essential for LWIR FPAs as broad intra-scene dynamic range imaging requires high sensitivity. The ROIC, featuring a 320x256 array with 25μm pixel pitch, has been designed in a standard 0.18μm CMOS technology. The main design challenges for this digital pixel array (SNR, power consumption and layout density) are discussed. The IC has been hybridized to a LWIR detector fabricated using our in-house HgCdTe process. The first electro-optical test results of the detector dewar assembly are presented. They validate both the pixel-level ADC concept and its circuit implementation. Finally, the benefit of this LWIR FPA in terms of NETD performance is demonstrated.

Evolution of the ATLAS distributed computing system during the LHC long shutdown

NASA Astrophysics Data System (ADS)

Campana, S.; Atlas Collaboration

2014-06-01

The ATLAS Distributed Computing project (ADC) was established in 2007 to develop and operate a framework, following the ATLAS computing model, to enable data storage, processing and bookkeeping on top of the Worldwide LHC Computing Grid (WLCG) distributed infrastructure. ADC development has always been driven by operations and this contributed to its success. The system has fulfilled the demanding requirements of ATLAS, daily consolidating worldwide up to 1 PB of data and running more than 1.5 million payloads distributed globally, supporting almost one thousand concurrent distributed analysis users. Comprehensive automation and monitoring minimized the operational manpower required. The flexibility of the system to adjust to operational needs has been important to the success of the ATLAS physics program. The LHC shutdown in 2013-2015 affords an opportunity to improve the system in light of operational experience and scale it to cope with the demanding requirements of 2015 and beyond, most notably a much higher trigger rate and event pileup. We will describe the evolution of the ADC software foreseen during this period. This includes consolidating the existing Production and Distributed Analysis framework (PanDA) and ATLAS Grid Information System (AGIS), together with the development and commissioning of next generation systems for distributed data management (DDM/Rucio) and production (Prodsys-2). We will explain how new technologies such as Cloud Computing and NoSQL databases, which ATLAS investigated as R&D projects in past years, will be integrated in production. Finally, we will describe more fundamental developments such as breaking job-to-data locality by exploiting storage federations and caches, and event level (rather than file or dataset level) workload engines.

Grading of Gliomas by Using Radiomic Features on Multiple Magnetic Resonance Imaging (MRI) Sequences.

PubMed

Qin, Jiang-Bo; Liu, Zhenyu; Zhang, Hui; Shen, Chen; Wang, Xiao-Chun; Tan, Yan; Wang, Shuo; Wu, Xiao-Feng; Tian, Jie

2017-05-07

BACKGROUND Gliomas are the most common primary brain neoplasms. Misdiagnosis occurs in glioma grading due to an overlap in conventional MRI manifestations. The aim of the present study was to evaluate the power of radiomic features based on multiple MRI sequences - T2-Weighted-Imaging-FLAIR (FLAIR), T1-Weighted-Imaging-Contrast-Enhanced (T1-CE), and Apparent Diffusion Coefficient (ADC) map - in glioma grading, and to improve the power of glioma grading by combining features. MATERIAL AND METHODS Sixty-six patients with histopathologically proven gliomas underwent T2-FLAIR and T1WI-CE sequence scanning with some patients (n=63) also undergoing DWI scanning. A total of 114 radiomic features were derived with radiomic methods by using in-house software. All radiomic features were compared between high-grade gliomas (HGGs) and low-grade gliomas (LGGs). Features with significant statistical differences were selected for receiver operating characteristic (ROC) curve analysis. The relationships between significantly different radiomic features and glial fibrillary acidic protein (GFAP) expression were evaluated. RESULTS A total of 8 radiomic features from 3 MRI sequences displayed significant differences between LGGs and HGGs. FLAIR GLCM Cluster Shade, T1-CE GLCM Entropy, and ADC GLCM Homogeneity were the best features to use in differentiating LGGs and HGGs in each MRI sequence. The combined feature was best able to differentiate LGGs and HGGs, which improved the accuracy of glioma grading compared to the above features in each MRI sequence. A significant correlation was found between GFAP and T1-CE GLCM Entropy, as well as between GFAP and ADC GLCM Homogeneity. CONCLUSIONS The combined radiomic feature had the highest efficacy in distinguishing LGGs from HGGs.

Wireless, battery-operated data acquisition system for mobile spectrometry applications and (potentially) for the Internet of things

NASA Astrophysics Data System (ADS)

Fitzgerald, Ryan; Karanassios, Vassili

2017-05-01

There are many applications requiring chemical analysis in the field and analytical results in (near) real-time. For example, when accidental spills occur. In others, collecting samples in the field followed by analysis in a lab increases costs and introduces time-delays. In such cases, "bring part of the lab to the sample" would be ideal. Toward this ideal (and to further reduce size and weight), we developed a relatively inexpensive, battery-operated, wireless data acquisition hardware system around an Arduino nano micro-controller and a 16-bit ADC (Analog-to- Digital Converter) with a max sampling rate of 860 samples/s. The hardware communicates the acquired data using low-power Bluetooth. Software for data acquisition and data display was written in Python. Potential ways of making the hardware-software approach described here a part of the Internet-of-Things (IoT) are presented.

New system for digital to analog transformation and reconstruction of 12-lead ECGs.

PubMed

Kothadia, Roshni; Kulecz, Walter B; Kofman, Igor S; Black, Adam J; Grier, James W; Schlegel, Todd T

2013-01-01

We describe initial validation of a new system for digital to analog conversion (DAC) and reconstruction of 12-lead ECGs. The system utilizes an open and optimized software format with a commensurately optimized DAC hardware configuration to accurately reproduce, from digital files, the original analog electrocardiographic signals of previously instrumented patients. By doing so, the system also ultimately allows for transmission of data collected on one manufacturer's 12-lead ECG hardware/software into that of any other. To initially validate the system, we compared original and post-DAC re-digitized 12-lead ECG data files (∼5-minutes long) in two types of validation studies in 10 patients. The first type quantitatively compared the total waveform voltage differences between the original and re-digitized data while the second type qualitatively compared the automated electrocardiographic diagnostic statements generated by the original versus re-digitized data. The grand-averaged difference in root mean squared voltage between the original and re-digitized data was 20.8 µV per channel when re-digitization involved the same manufacturer's analog to digital converter (ADC) as the original digitization, and 28.4 µV per channel when it involved a different manufacturer's ADC. Automated diagnostic statements generated by the original versus reconstructed data did not differ when using the diagnostic algorithm from the same manufacturer on whose device the original data were collected, and differed only slightly for just 1 of 10 patients when using a third-party diagnostic algorithm throughout. Original analog 12-lead ECG signals can be reconstructed from digital data files with accuracy sufficient for clinical use. Such reconstructions can readily enable automated second opinions for difficult-to-interpret 12-lead ECGs, either locally or remotely through the use of dedicated or cloud-based servers.

Breast lesion characterization using whole-lesion histogram analysis with stretched-exponential diffusion model.

PubMed

Liu, Chunling; Wang, Kun; Li, Xiaodan; Zhang, Jine; Ding, Jie; Spuhler, Karl; Duong, Timothy; Liang, Changhong; Huang, Chuan

2018-06-01

Diffusion-weighted imaging (DWI) has been studied in breast imaging and can provide more information about diffusion, perfusion and other physiological interests than standard pulse sequences. The stretched-exponential model has previously been shown to be more reliable than conventional DWI techniques, but different diagnostic sensitivities were found from study to study. This work investigated the characteristics of whole-lesion histogram parameters derived from the stretched-exponential diffusion model for benign and malignant breast lesions, compared them with conventional apparent diffusion coefficient (ADC), and further determined which histogram metrics can be best used to differentiate malignant from benign lesions. This was a prospective study. Seventy females were included in the study. Multi-b value DWI was performed on a 1.5T scanner. Histogram parameters of whole lesions for distributed diffusion coefficient (DDC), heterogeneity index (α), and ADC were calculated by two radiologists and compared among benign lesions, ductal carcinoma in situ (DCIS), and invasive carcinoma confirmed by pathology. Nonparametric tests were performed for comparisons among invasive carcinoma, DCIS, and benign lesions. Comparisons of receiver operating characteristic (ROC) curves were performed to show the ability to discriminate malignant from benign lesions. The majority of histogram parameters (mean/min/max, skewness/kurtosis, 10-90 th percentile values) from DDC, α, and ADC were significantly different among invasive carcinoma, DCIS, and benign lesions. DDC 10% (area under curve [AUC] = 0.931), ADC 10% (AUC = 0.893), and α mean (AUC = 0.787) were found to be the best metrics in differentiating benign from malignant tumors among all histogram parameters derived from ADC and α, respectively. The combination of DDC 10% and α mean , using logistic regression, yielded the highest sensitivity (90.2%) and specificity (95.5%). DDC 10% and α mean derived from the stretched-exponential model provides more information and better diagnostic performance in differentiating malignancy from benign lesions than ADC parameters derived from a monoexponential model. 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;47:1701-1710. © 2017 International Society for Magnetic Resonance in Medicine.

MRI diffusion-weighted imaging (DWI) in pediatric small bowel Crohn disease: correlation with MRI findings of active bowel wall inflammation.

PubMed

Ream, Justin M; Dillman, Jonathan R; Adler, Jeremy; Khalatbari, Shokoufeh; McHugh, Jonathan B; Strouse, Peter J; Dhanani, Muhammad; Shpeen, Benjamin; Al-Hawary, Mahmoud M

2013-09-01

Restricted diffusion on diffusion-weighted imaging (DWI) sequences during magnetic resonance enterography (MRE) has been shown in segments of bowel affected by Crohn disease. However, the exact meaning of this finding, particularly within the pediatric Crohn disease population, is poorly understood. The purpose of this study was to determine the significance of bowel wall restricted diffusion in children with small bowel Crohn disease by correlating apparent diffusion coefficient (ADC) values with other MRI markers of disease activity. A retrospective review of pediatric patients (≤ 18 years of age) with Crohn disease terminal ileitis who underwent MRE with DWI at our institution between May 1, 2009 and May 31, 2011 was undertaken. All of the children had either biopsy-proven Crohn disease terminal ileitis or clinically diagnosed Crohn disease, including terminal ileal involvement by imaging. The mean minimum ADC value within the wall of the terminal ileum was determined for each examination. ADC values were tested for correlation/association with other MRI findings to determine whether a relationship exists between bowel wall restricted diffusion and disease activity. Forty-six MRE examinations with DWI in children with terminal ileitis were identified (23 girls and 23 boys; mean age, 14.3 years). There was significant negative correlation or association between bowel wall minimum ADC value and established MRI markers of disease activity, including degree of bowel wall thickening (R = (-)0.43; P = 0.003), striated pattern of arterial enhancement (P = 0.01), degree of arterial enhancement (P = 0.01), degree of delayed enhancement (P = 0.045), amount of mesenteric inflammatory changes (P < 0.0001) and presence of a stricture (P = 0.02). ADC values were not significantly associated with bowel wall T2-weighted signal intensity, length of disease involvement or mesenteric fibrofatty proliferation. Increasing bowel wall restricted diffusion (lower ADC values) is associated with multiple MRI findings that are traditionally associated with active inflammation in pediatric small bowel Crohn disease.

Contrast-enhanced dynamic and diffusion-weighted magnetic resonance imaging at 3.0 T to assess early-stage nasopharyngeal carcinoma.

PubMed

Ni, Liangping; Liu, Ying

2018-04-01

The present study aimed to assess early-stage nasopharyngeal carcinoma (NPC) with dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and diffusion-weighted imaging (DWI) at 3.0 T. A total of 44 patients newly diagnosed with NPC were included in the present study. All patients underwent MR examination at 3.0 T using DCE-MRI and DWI. The volume transfer constant ( K trans ), flux rate constant between extravascular extracellular space and plasma ( K ep ), the volume of extravascular extracellular space per unit volume of tissue ( V e ) and the apparent diffusion coefficient (ADC) of tumours were investigated. Furthermore, the correlation between clinical stages and ADC value and K trans were analysed. The diagnostic accuracy of K trans and ADC were estimated using receiver operating characteristic curves. NPC stage correlated positively with K trans and negatively with ADC values. Additionally, tumour K trans negatively correlated with ADC value. The sensitivity and accuracy of combined K trans and ADC in distinguishing between stage II and stage III and stage III and IV were higher than the values of either measurement used separately. The present study suggested that K trans and ADC derived from DCE-MRI and DWI may be useful to detect stage early NPC accurately. K trans and ADC in combination were superior than either alone.

A comparative quantitative analysis of magnetic susceptibility artifacts in echo planar and PROPELLER diffusion-weighted images

NASA Astrophysics Data System (ADS)

Cho, Jae-Hwan; Lee, Hae-Kag; Yang, Han-Joon; Lee, Gui-Won; Park, Yong-Soon; Chung, Woon-Kwan

2013-01-01

In this study, the authors investigated whether periodically-rotated overlapping parallel lines with enhanced reconstruction (PROPELLER) diffusion-weighted imaging (DWI) can remove magnetic susceptibility artifacts and compared apparent diffusion coefficient (ADC) values for PROPELLER DWI and the common echo planar (EP) DWI. Twenty patients that underwent brain MRI with a metal dental implant were selected. A 3.0T MR scanner was then used to obtain EP DWI, PROPELLER DWI, and corresponding apparent diffusion coefficient (ADC) maps for a b-value of 0 and 1,000 s/mm2. The frequencies of magnetic susceptibility artifacts in four parts of the brain (bilateral temporal lobes, pons, and orbit) were selected. In the ADC maps, we measured the ADC values of both sides of the temporal lobe and the pons. According to the study results, the frequency of magnetic susceptibility artifacts in PROPELLER DW images was lower than it was in EP DW images. In ADC maps, the ADC values of the bilateral temporal lobes and the pons were all higher in PROPELLER ADC maps than in EP ADC maps. Our findings show that when a high-field MRI machine is used, magnetic susceptibility artifacts can distort anatomical structures and produce high-intensity signals. Furthermore, our findings suggest that in many cases, PROPELLER DWI would be helpful in terms of achieving a correct diagnosis.

Regional ADC values of the normal brain: differences due to age, gender, and laterality.

PubMed

Naganawa, Shinji; Sato, Kimihide; Katagiri, Toshio; Mimura, Takeo; Ishigaki, Takeo

2003-01-01

The purpose of this study was to evaluate the stability of measurement for apparent diffusion coefficient (ADC) values in normal brain, to clarify the effect of aging on ADC values, to compare ADC values between men and women, and to compare ADC values between right and left sides of the brain. To evaluate the stability of measurements, five normal volunteers (four men and one woman) were examined five times on different days. Then, 294 subjects with normal MR imaging (147 men and 147 women; age range 20-89 years) were measured. The ADC measurement in normal volunteers was stable. The ADC values stayed within the 5% deviation of average values in all volunteers (mean+/-standard deviation 2.3+/-1.2%). The ADC values gradually increased by aging in all regions. In thalamus, no significant difference was seen between right and left in the subjects under 60 years; however, right side showed higher values in the subjects over 60 years (p<0.01). In the subjects under 60 years, women showed higher values in right frontal, bilateral thalamus, and temporal (p<0.01); however, in the subjects over 60 years, no region showed difference between men and women. The knowledge obtained in this study may be helpful to understand the developmental and aging mechanisms of normal brain and may be useful for the future quantitative study as a reference.

Analysis and correction of gradient nonlinearity bias in ADC measurements

PubMed Central

Malyarenko, Dariya I.; Ross, Brian D.; Chenevert, Thomas L.

2013-01-01

Purpose Gradient nonlinearity of MRI systems leads to spatially-dependent b-values and consequently high non-uniformity errors (10–20%) in ADC measurements over clinically relevant field-of-views. This work seeks practical correction procedure that effectively reduces observed ADC bias for media of arbitrary anisotropy in the fewest measurements. Methods All-inclusive bias analysis considers spatial and time-domain cross-terms for diffusion and imaging gradients. The proposed correction is based on rotation of the gradient nonlinearity tensor into the diffusion gradient frame where spatial bias of b-matrix can be approximated by its Euclidean norm. Correction efficiency of the proposed procedure is numerically evaluated for a range of model diffusion tensor anisotropies and orientations. Results Spatial dependence of nonlinearity correction terms accounts for the bulk (75–95%) of ADC bias for FA = 0.3–0.9. Residual ADC non-uniformity errors are amplified for anisotropic diffusion. This approximation obviates need for full diffusion tensor measurement and diagonalization to derive a corrected ADC. Practical scenarios are outlined for implementation of the correction on clinical MRI systems. Conclusions The proposed simplified correction algorithm appears sufficient to control ADC non-uniformity errors in clinical studies using three orthogonal diffusion measurements. The most efficient reduction of ADC bias for anisotropic medium is achieved with non-lab-based diffusion gradients. PMID:23794533

Recent Advances in Antibody-Drug Conjugates for Breast Cancer Treatment.

PubMed

Deng, Shanshan; Lin, Zongtao; Li, Wei

2017-01-01

Breast cancer is the most common cancer in women, with roughly half a million deaths per year worldwide. Among various approaches for breast cancer treatment, chemotherapy is predominantly used for patients at stages II-IV, and monoclonal antibody (mAb) therapy is used for patients with human epidermal growth factor receptor 2 (HER2) overexpression. Integrating the tumor specificity provided by unique mAbs and cytotoxicity of small molecule drugs, antibody-drug conjugates (ADCs) are a series of smart chemotherapeutics that have recently shown great promise in treating a number of cancer types. ADCs are designed to selectively attack and kill cancer cells with minimal toxicity to normal tissues. Ado-Trastuzumab emtansine (T-DM1) was the first and only ADC approved by the US Food and Drug Administration for HER2-positive breast cancer. Following the success of T-DM1, many novel ADCs have been developed, and their anticancer efficacies are currently undergoing preclinical or clinical investigation. The development of ADCs is a rapidly progressing field, and this review aims to summarize the most recent advances in ADCs targeting breast cancer over the past five years (2011-2016). The review highlights compositions and mechanisms of action of these newly developed ADCs and discusses current challenges and future directions of developing new ADCs for improved treatment of breast cancer. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Decreased apparent diffusion coefficient in the pituitary and correlation with hypopituitarism in patients with traumatic brain injury.

PubMed

Zheng, Ping; He, Bin; Guo, Yijun; Zeng, Jingsong; Tong, Wusong

2015-07-01

The relationship between microstructural abnormality in patients with traumatic brain injury (TBI) and hormone-secreting status remains unknown. In this study, the authors aimed to identify the role of the apparent diffusion coefficient (ADC) using a diffusion-weighted imaging (DWI) technique and to evaluate the association of such changes with hypopituitarism in patients with TBI. Diffusion-weighted images were obtained in 164 consecutive patients with TBI within 2 weeks after injury to generate the pituitary ADC as a measure of microstructural change. Patients with TBI were further grouped into those with and those without hypopituitarism based on the secretion status of pituitary hormones at 6 months postinjury. Thirty healthy individuals were enrolled in the study and underwent MRI examinations for comparison. Mean ADC values were compared between this control group, the patients with TBI and hypopituitarism, and the patients with TBI without hypopituitarism; correlational studies were also performed. Neurological outcome was assessed with the Glasgow Outcome Scale (GOS) for all TBI patients 6 months postinjury. In the TBI group, 84 patients had hypopituitarism and 80 had normal pituitary function. The pituitary ADC in TBI patients was significantly less than that in controls (1.83 ± 0.16 vs 4.13 ± 0.33, p < 0.01). Furthermore, the mean ADC was much lower in TBI patients with hypopituitarism than in those without pituitary dysfunction (1.32 ± 0.09 vs 2.28 ± 0.17, p < 0.05). There was also a significant difference in ADC values between patients with hyperprolactinemia and those with normal prolactin levels (p < 0.05). Additionally, the receiver operating characteristic curve analysis showed that the pituitary ADC could predict hypopituitarism with a sensitivity of 90.0% and a specificity of 90.1% at the level of 1.720 (ADC value). Finally, the ADC value was positively correlated with neurological outcome at 6 months following TBI (r = 0.602, p < 0.05). Use of DWI demonstrated that the pituitary ADC is correlated with hormone-secreting status in TBI patients. The authors suggest that pituitary ADC may be a useful biomarker to predict pituitary function in patients with TBI.

Cathepsin B Cleavage of vcMMAE-Based Antibody-Drug Conjugate Is Not Drug Location or Monoclonal Antibody Carrier Specific.

PubMed

Gikanga, Benson; Adeniji, Nia S; Patapoff, Thomas W; Chih, Hung-Wei; Yi, Li

2016-04-20

Antibody-drug conjugates (ADCs) require thorough characterization and understanding of product quality attributes. The framework of many ADCs comprises one molecule of antibody that is usually conjugated with multiple drug molecules at various locations. It is unknown whether the drug release rate from the ADC is dependent on drug location, and/or local environment, dictated by the sequence and structure of the antibody carrier. This study addresses these issues with valine-citrulline-monomethylauristatin E (vc-MMAE)-based ADC molecules conjugated at reduced disulfide bonds, by evaluating the cathepsin B catalyzed drug release rate of ADC molecules with different drug distributions or antibody carriers. MMAE drug release rates at different locations on ADC I were compared to evaluate the impact of drug location. No difference in rates was observed for drug released from the V(H), V(L), or C(H)2 domains of ADC I. Furthermore, four vc-MMAE ADC molecules were chosen as substrates for cathepsin B for evaluation of Michaelis-Menten parameters. There was no significant difference in K(M) or k(cat) values, suggesting that different sequences of the antibody carrier do not result in different drug release rates. Comparison between ADCs and small molecules containing vc-MMAE moieties as substrates for cathepsin B suggests that the presence of IgG1 antibody carrier, regardless of its bulkiness, does not impact drug release rate. Finally, a molecular dynamics simulation on ADC II revealed that the val-cit moiety at each of the eight possible conjugation sites was, on average, solvent accessible over 50% of its maximum solvent accessible surface area (SASA) during a 500 ns trajectory. Combined, these results suggest that the cathepsin cleavage sites for conjugated drugs are exposed enough for the enzyme to access and that the drug release rate is rather independent of drug location or monoclonal antibody carrier. Therefore, the distribution of drug conjugation at different sites is not a critical parameter to control in manufacturing of the vc-MMAE-based ADC conjugated at reduced disulfide bonds.

Establishing an EGFR mutation screening service for non-small cell lung cancer - sample quality criteria and candidate histological predictors.

PubMed

Leary, Alexandra F; Castro, David Gonzalez de; Nicholson, Andrew G; Ashley, Sue; Wotherspoon, Andrew; O'Brien, Mary E R; Popat, Sanjay

2012-01-01

EGFR screening requires good quality tissue, sensitivity and turn-around time (TAT). We report our experience of routine screening, describing sample type, TAT, specimen quality (cellularity and DNA yield), histopathological description, mutation result and clinical outcome. Non-small cell lung cancer (NSCLC) sections were screened for EGFR mutations (M+) in exons 18-21. Clinical, pathological and screening outcome data were collected for year 1 of testing. Screening outcome alone was collected for year 2. In year 1, 152 samples were tested, most (72%) were diagnostic. TAT was 4.9 days (95%confidence interval (CI)=4.5-5.5). EGFR-M+ prevalence was 11% and higher (20%) among never-smoking women with adenocarcinomas (ADCs), but 30% of mutations occurred in current/ex-smoking men. EGFR-M+ tumours were non-mucinous ADCs and 100% thyroid transcription factor (TTF1+). No mutations were detected in poorly differentiated NSCLC-not otherwise specified (NOS). There was a trend for improved overall survival (OS) among EGFR-M+ versus EGFR-M- patients (median OS=78 versus 17 months). In year 1, test failure rate was 19%, and associated with scant cellularity and low DNA concentrations. However 75% of samples with poor cellularity but representative of tumour were informative and mutation prevalence was 9%. In year 2, 755 samples were tested; mutation prevalence was 13% and test failure only 5.4%. Although samples with low DNA concentration (<2 ng/μL) had more test failures (30% versus 3.9% for [DNA]>2.2 ng/μL), the mutation rate was 9.2%. Routine epidermal growth factor receptor (EGFR) screening using diagnostic samples is fast and feasible even on samples with poor cellularity and DNA content. Mutations tend to occur in better-differentiated non-mucinous TTF1+ ADCs. Whether these histological criteria may be useful to select patients for EGFR testing merits further investigation. Copyright © 2011 Elsevier Ltd. All rights reserved.

Implementation of integrated circuit and design of SAR ADC for fully implantable hearing aids.

PubMed

Kim, Jong Hoon; Lee, Jyung Hyun; Cho, Jin-Ho

2017-07-20

The hearing impaired population has been increasing; many people suffer from hearing problems. To deal with this difficulty, various types of hearing aids are being rapidly developed. In particular, fully implantable hearing aids are being actively studied to improve the performance of existing hearing aids and to reduce the stigma of hearing loss patients. It has to be of small size and low-power consumption for easy implantation and long-term use. The objective of the study was to implement a small size and low-power consumption successive approximation register analog-to-digital converter (SAR ADC) for fully implantable hearing aids. The ADC was selected as the SAR ADC because its analog circuit components are less required by the feedback circuit of the SAR ADC than the sigma-delta ADC which is conventionally used in hearing aids, and it has advantages in the area and power consumption. So, the circuit of SAR ADC is designed considering the speech region of humans because the objective is to deliver the speech signals of humans to hearing loss patients. If the switch of sample and hold works in the on/off positions, the charge injection and clock feedthrough are produced by a parasitic capacitor. These problems affect the linearity of the hold voltage, and as a result, an error of the bit conversion is generated. In order to solve the problem, a CMOS switch that consists of NMOS and PMOS was used, and it reduces the charge injection because the charge carriers in the NMOS and PMOS have inversed polarity. So, 16 bit conversion is performed before the occurrence of the Least Significant Bit (LSB) error. In order to minimize the offset voltage and power consumption of the designed comparator, we designed a preamplifier with current mirror. Therefore, the power consumption was reduced by the power control switch used in the comparator. The layout of the designed SAR ADC was performed by Virtuoso Layout Editor (Cadence, USA). In the layout result, the size of the designed SAR ADC occupied 124.9 μm × 152.1 μm. The circuit verification was performed by layout versus schematic (LVS) and design rule check (DRC) which are provided by Calibre (Mentor Graphics, USA), and it was confirmed that there was no error. The designed SAR ADC was implemented in SMIC 180 nm CMOS technology. The operation of the manufactured SAR ADC was confirmed by using an oscilloscope. The SAR ADC output was measured using a distortion meter (HM 8027), when applying pure tone sounds of 94 dB SPL at 500, 800, and 1600 Hz regions. As a result, the THD performance of the proposed chip was satisfied with the ANSI. s3. 22. 2003 standard. We proposed a low-power 16-bit 32 kHz SAR ADC for fully implantable hearing aids. The manufactured SAR ADC based on this design was confirmed to have advantages in power consumption and size through the comparison with the conventional ADC. Therefore, the manufactured SAR ADC is expected to be used in the implantable medical device field and speech signal processing field, which require small size and low power consumption.

Computer aided detection in prostate cancer diagnostics: A promising alternative to biopsy? A retrospective study from 104 lesions with histological ground truth.

PubMed

Thon, Anika; Teichgräber, Ulf; Tennstedt-Schenk, Cornelia; Hadjidemetriou, Stathis; Winzler, Sven; Malich, Ansgar; Papageorgiou, Ismini

2017-01-01

Prostate cancer (PCa) diagnosis by means of multiparametric magnetic resonance imaging (mpMRI) is a current challenge for the development of computer-aided detection (CAD) tools. An innovative CAD-software (Watson Elementary™) was proposed to achieve high sensitivity and specificity, as well as to allege a correlate to Gleason grade. To assess the performance of Watson Elementary™ in automated PCa diagnosis in our hospital´s database of MRI-guided prostate biopsies. The evaluation was retrospective for 104 lesions (47 PCa, 57 benign) from 79, 64.61±6.64 year old patients using 3T T2-weighted imaging, Apparent Diffusion Coefficient (ADC) maps and dynamic contrast enhancement series. Watson Elementary™ utilizes signal intensity, diffusion properties and kinetic profile to compute a proportional Gleason grade predictor, termed Malignancy Attention Index (MAI). The analysis focused on (i) the CAD sensitivity and specificity to classify suspect lesions and (ii) the MAI correlation with the histopathological ground truth. The software revealed a sensitivity of 46.80% for PCa classification. The specificity for PCa was found to be 75.43% with a positive predictive value of 61.11%, a negative predictive value of 63.23% and a false discovery rate of 38.89%. CAD classified PCa and benign lesions with equal probability (P 0.06, χ2 test). Accordingly, receiver operating characteristic analysis suggests a poor predictive value for MAI with an area under curve of 0.65 (P 0.02), which is not superior to the performance of board certified observers. Moreover, MAI revealed no significant correlation with Gleason grade (P 0.60, Pearson´s correlation). The tested CAD software for mpMRI analysis was a weak PCa biomarker in this dataset. Targeted prostate biopsy and histology remains the gold standard for prostate cancer diagnosis.

Computer aided detection in prostate cancer diagnostics: A promising alternative to biopsy? A retrospective study from 104 lesions with histological ground truth

PubMed Central

Thon, Anika; Teichgräber, Ulf; Tennstedt-Schenk, Cornelia; Hadjidemetriou, Stathis; Winzler, Sven; Malich, Ansgar

2017-01-01

Background Prostate cancer (PCa) diagnosis by means of multiparametric magnetic resonance imaging (mpMRI) is a current challenge for the development of computer-aided detection (CAD) tools. An innovative CAD-software (Watson Elementary™) was proposed to achieve high sensitivity and specificity, as well as to allege a correlate to Gleason grade. Aim/Objective To assess the performance of Watson Elementary™ in automated PCa diagnosis in our hospital´s database of MRI-guided prostate biopsies. Methods The evaluation was retrospective for 104 lesions (47 PCa, 57 benign) from 79, 64.61±6.64 year old patients using 3T T2-weighted imaging, Apparent Diffusion Coefficient (ADC) maps and dynamic contrast enhancement series. Watson Elementary™ utilizes signal intensity, diffusion properties and kinetic profile to compute a proportional Gleason grade predictor, termed Malignancy Attention Index (MAI). The analysis focused on (i) the CAD sensitivity and specificity to classify suspect lesions and (ii) the MAI correlation with the histopathological ground truth. Results The software revealed a sensitivity of 46.80% for PCa classification. The specificity for PCa was found to be 75.43% with a positive predictive value of 61.11%, a negative predictive value of 63.23% and a false discovery rate of 38.89%. CAD classified PCa and benign lesions with equal probability (P 0.06, χ2 test). Accordingly, receiver operating characteristic analysis suggests a poor predictive value for MAI with an area under curve of 0.65 (P 0.02), which is not superior to the performance of board certified observers. Moreover, MAI revealed no significant correlation with Gleason grade (P 0.60, Pearson´s correlation). Conclusion The tested CAD software for mpMRI analysis was a weak PCa biomarker in this dataset. Targeted prostate biopsy and histology remains the gold standard for prostate cancer diagnosis. PMID:29023572

Treatment with the C5a receptor antagonist ADC-1004 reduces myocardial infarction in a porcine ischemia-reperfusion model

PubMed Central

2010-01-01

Background Polymorphonuclear neutrophils, stimulated by the activated complement factor C5a, have been implicated in cardiac ischemia/reperfusion injury. ADC-1004 is a competitive C5a receptor antagonist that has been shown to inhibit complement related neutrophil activation. ADC-1004 shields the neutrophils from C5a activation before they enter the reperfused area, which could be a mechanistic advantage compared to previous C5a directed reperfusion therapies. We investigated if treatment with ADC-1004, according to a clinically applicable protocol, would reduce infarct size and microvascular obstruction in a large animal myocardial infarct model. Methods In anesthetized pigs (42-53 kg), a percutaneous coronary intervention balloon was inflated in the left anterior descending artery for 40 minutes, followed by 4 hours of reperfusion. Twenty minutes after balloon inflation the pigs were randomized to an intravenous bolus administration of ADC-1004 (175 mg, n = 8) or saline (9 mg/ml, n = 8). Area at risk (AAR) was evaluated by ex vivo SPECT. Infarct size and microvascular obstruction were evaluated by ex vivo MRI. The observers were blinded to the treatment at randomization and analysis. Results ADC-1004 treatment reduced infarct size by 21% (ADC-1004: 58.3 ± 3.4 vs control: 74.1 ± 2.9%AAR, p = 0.007). Microvascular obstruction was similar between the groups (ADC-1004: 2.2 ± 1.2 vs control: 5.3 ± 2.5%AAR, p = 0.23). The mean plasma concentration of ADC-1004 was 83 ± 8 nM at sacrifice. There were no significant differences between the groups with respect to heart rate, mean arterial pressure, cardiac output and blood-gas data. Conclusions ADC-1004 treatment reduces myocardial ischemia-reperfusion injury and represents a novel treatment strategy of myocardial infarct with potential clinical applicability. PMID:20875134

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

Engstroem, K; Casares-Magaz, O; Muren, L

Purpose: Multi-parametric MRI (mp-MRI) is being introduced in radiotherapy (RT) of prostate cancer, including for tumour delineation in focal boosting strategies. We recently developed an image-based tumour control probability model, based on cell density distributions derived from apparent diffusion coefficient (ADC) maps. Beyond tumour volume and cell densities, tumour hypoxia is also an important determinant of RT response. Since tissue perfusion from mp-MRI has been related to hypoxia we have explored the patterns of ADC and perfusion maps, and the relations between them, inside and outside prostate index lesions. Methods: ADC and perfusion maps from 20 prostate cancer patients weremore » used, with the prostate and index lesion delineated by a dedicated uro-radiologist. To reduce noise, the maps were averaged over a 3×3×3 voxel cube. Associations between different ADC and perfusion histogram parameters within the prostate, inside and outside the index lesion, were evaluated with the Pearson’s correlation coefficient. In the voxel-wise analysis, scatter plots of ADC vs perfusion were analysed for voxels in the prostate, inside and outside of the index lesion, again with the associations quantified with the Pearson’s correlation coefficient. Results: Overall ADC was lower inside the index lesion than in the normal prostate as opposed to ktrans that was higher inside the index lesion than outside. In the histogram analysis, the minimum ktrans was significantly correlated with the maximum ADC (Pearson=0.47; p=0.03). At the voxel level, 15 of the 20 cases had a statistically significant inverse correlation between ADC and perfusion inside the index lesion; ten of the cases had a Pearson < −0.4. Conclusion: The minimum value of ktrans across the tumour was correlated to the maximum ADC. However, on the voxel level, the ‘local’ ktrans in the index lesion is inversely (i.e. negatively) correlated to the ‘local’ ADC in most patients. Research agreement with Varian Medical Systems, not related to the work presented in this abstract.« less

Treatment with the C5a receptor antagonist ADC-1004 reduces myocardial infarction in a porcine ischemia-reperfusion model.

PubMed

van der Pals, Jesper; Koul, Sasha; Andersson, Patrik; Götberg, Matthias; Ubachs, Joey F A; Kanski, Mikael; Arheden, Håkan; Olivecrona, Göran K; Larsson, Bengt; Erlinge, David

2010-09-27

Polymorphonuclear neutrophils, stimulated by the activated complement factor C5a, have been implicated in cardiac ischemia/reperfusion injury. ADC-1004 is a competitive C5a receptor antagonist that has been shown to inhibit complement related neutrophil activation. ADC-1004 shields the neutrophils from C5a activation before they enter the reperfused area, which could be a mechanistic advantage compared to previous C5a directed reperfusion therapies. We investigated if treatment with ADC-1004, according to a clinically applicable protocol, would reduce infarct size and microvascular obstruction in a large animal myocardial infarct model. In anesthetized pigs (42-53 kg), a percutaneous coronary intervention balloon was inflated in the left anterior descending artery for 40 minutes, followed by 4 hours of reperfusion. Twenty minutes after balloon inflation the pigs were randomized to an intravenous bolus administration of ADC-1004 (175 mg, n = 8) or saline (9 mg/ml, n = 8). Area at risk (AAR) was evaluated by ex vivo SPECT. Infarct size and microvascular obstruction were evaluated by ex vivo MRI. The observers were blinded to the treatment at randomization and analysis. ADC-1004 treatment reduced infarct size by 21% (ADC-1004: 58.3 ± 3.4 vs control: 74.1 ± 2.9%AAR, p = 0.007). Microvascular obstruction was similar between the groups (ADC-1004: 2.2 ± 1.2 vs control: 5.3 ± 2.5%AAR, p = 0.23). The mean plasma concentration of ADC-1004 was 83 ± 8 nM at sacrifice. There were no significant differences between the groups with respect to heart rate, mean arterial pressure, cardiac output and blood-gas data. ADC-1004 treatment reduces myocardial ischemia-reperfusion injury and represents a novel treatment strategy of myocardial infarct with potential clinical applicability.

Anal Cancer Incidence in the United States, 1977–2011: Distinct Patterns by Histology and Behavior

PubMed Central

Shiels, Meredith S.; Kreimer, Aimée R.; Coghill, Anna E.; Darragh, Teresa M.; Devesa, Susan S.

2015-01-01

Background Although anal squamous cell carcinoma (SCC) and adenocarcinoma (ADC) are generally combined in cancer surveillance, their etiologies likely differ. Here, we describe demographic characteristics and trends in incidence rates (IRs) of anal cancer by histology (SCC, ADC) and behavior (invasive, in situ) in the United States. Methods With data from the Surveillance, Epidemiology and End Results (SEER) Program, we estimated age-adjusted anal cancer IRs across behavior/histology by demographic and tumor characteristics for 2000–2011. Trends in IRs and annual percent changes during 1977–2011 were also estimated and compared to rectal cancer. Results Women had higher rates of SCC (rate ratio [RR]=1.45; 95%CI 1.40–1.50) and lower rates of ADC (RR=0.68; 95%CI 0.62–0.74) and squamous carcinoma in situ (CIS) (RR=0.36; 95%CI 0.34–0.38) than men. Blacks had lower rates of SCC (RR=0.82; 95%CI 0.77–0.87) and CIS (RR=0.90; 95%CI 0.83–0.98) than non-Hispanic whites, but higher rates of ADC (RR=1.48; 95%CI 1.29–1.70). Anal cancer IRs were higher in men and blacks aged <40 years. During 1992–2011, SCC IRs increased 2.9%/year, ADC IRs declined non-significantly, and CIS IRs rose 14.2%/year. SCC and ADC IR patterns and trends were similar across anal and rectal cancers. Conclusions Rates of anal SCC and CIS have increased strongly over time, in contrast to rates of anal ADC, similar to trends observed for rectal SCC and ADC. Impact Anal SCC and ADC likely have different etiologies, but may have similar etiologies to rectal SCC and ADC, respectively. Strong increases in CIS IRs over time may reflect anal cancer screening patterns. PMID:26224796

B-spline algebraic diagrammatic construction: Application to photoionization cross-sections and high-order harmonic generation

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

Ruberti, M.; Averbukh, V.; Decleva, P.

2014-10-28

We present the first implementation of the ab initio many-body Green's function method, algebraic diagrammatic construction (ADC), in the B-spline single-electron basis. B-spline versions of the first order [ADC(1)] and second order [ADC(2)] schemes for the polarization propagator are developed and applied to the ab initio calculation of static (photoionization cross-sections) and dynamic (high-order harmonic generation spectra) quantities. We show that the cross-section features that pose a challenge for the Gaussian basis calculations, such as Cooper minima and high-energy tails, are found to be reproduced by the B-spline ADC in a very good agreement with the experiment. We also presentmore » the first dynamic B-spline ADC results, showing that the effect of the Cooper minimum on the high-order harmonic generation spectrum of Ar is correctly predicted by the time-dependent ADC calculation in the B-spline basis. The present development paves the way for the application of the B-spline ADC to both energy- and time-resolved theoretical studies of many-electron phenomena in atoms, molecules, and clusters.« less

Target-mediated drug disposition model and its approximations for antibody-drug conjugates.

PubMed

Gibiansky, Leonid; Gibiansky, Ekaterina

2014-02-01

Antibody-drug conjugate (ADC) is a complex structure composed of an antibody linked to several molecules of a biologically active cytotoxic drug. The number of ADC compounds in clinical development now exceeds 30, with two of them already on the market. However, there is no rigorous mechanistic model that describes pharmacokinetic (PK) properties of these compounds. PK modeling of ADCs is even more complicated than that of other biologics as the model should describe distribution, binding, and elimination of antibodies with different toxin load, and also the deconjugation process and PK of the released toxin. This work extends the target-mediated drug disposition (TMDD) model to describe ADCs, derives the rapid binding (quasi-equilibrium), quasi-steady-state, and Michaelis-Menten approximations of the TMDD model as applied to ADCs, derives the TMDD model and its approximations for ADCs with load-independent properties, and discusses further simplifications of the system under various assumptions. The developed models are shown to describe data simulated from the available clinical population PK models of trastuzumab emtansine (T-DM1), one of the two currently approved ADCs. Identifiability of model parameters is also discussed and illustrated on the simulated T-DM1 examples.

A 12-bit high-speed column-parallel two-step single-slope analog-to-digital converter (ADC) for CMOS image sensors.

PubMed

Lyu, Tao; Yao, Suying; Nie, Kaiming; Xu, Jiangtao

2014-11-17

A 12-bit high-speed column-parallel two-step single-slope (SS) analog-to-digital converter (ADC) for CMOS image sensors is proposed. The proposed ADC employs a single ramp voltage and multiple reference voltages, and the conversion is divided into coarse phase and fine phase to improve the conversion rate. An error calibration scheme is proposed to correct errors caused by offsets among the reference voltages. The digital-to-analog converter (DAC) used for the ramp generator is based on the split-capacitor array with an attenuation capacitor. Analysis of the DAC's linearity performance versus capacitor mismatch and parasitic capacitance is presented. A prototype 1024 × 32 Time Delay Integration (TDI) CMOS image sensor with the proposed ADC architecture has been fabricated in a standard 0.18 μm CMOS process. The proposed ADC has average power consumption of 128 μW and a conventional rate 6 times higher than the conventional SS ADC. A high-quality image, captured at the line rate of 15.5 k lines/s, shows that the proposed ADC is suitable for high-speed CMOS image sensors.

Fast and Analytical EAP Approximation from a 4th-Order Tensor.

PubMed

Ghosh, Aurobrata; Deriche, Rachid

2012-01-01

Generalized diffusion tensor imaging (GDTI) was developed to model complex apparent diffusivity coefficient (ADC) using higher-order tensors (HOTs) and to overcome the inherent single-peak shortcoming of DTI. However, the geometry of a complex ADC profile does not correspond to the underlying structure of fibers. This tissue geometry can be inferred from the shape of the ensemble average propagator (EAP). Though interesting methods for estimating a positive ADC using 4th-order diffusion tensors were developed, GDTI in general was overtaken by other approaches, for example, the orientation distribution function (ODF), since it is considerably difficult to recuperate the EAP from a HOT model of the ADC in GDTI. In this paper, we present a novel closed-form approximation of the EAP using Hermite polynomials from a modified HOT model of the original GDTI-ADC. Since the solution is analytical, it is fast, differentiable, and the approximation converges well to the true EAP. This method also makes the effort of computing a positive ADC worthwhile, since now both the ADC and the EAP can be used and have closed forms. We demonstrate our approach with 4th-order tensors on synthetic data and in vivo human data.

Fast and Analytical EAP Approximation from a 4th-Order Tensor

PubMed Central

Ghosh, Aurobrata; Deriche, Rachid

2012-01-01

Generalized diffusion tensor imaging (GDTI) was developed to model complex apparent diffusivity coefficient (ADC) using higher-order tensors (HOTs) and to overcome the inherent single-peak shortcoming of DTI. However, the geometry of a complex ADC profile does not correspond to the underlying structure of fibers. This tissue geometry can be inferred from the shape of the ensemble average propagator (EAP). Though interesting methods for estimating a positive ADC using 4th-order diffusion tensors were developed, GDTI in general was overtaken by other approaches, for example, the orientation distribution function (ODF), since it is considerably difficult to recuperate the EAP from a HOT model of the ADC in GDTI. In this paper, we present a novel closed-form approximation of the EAP using Hermite polynomials from a modified HOT model of the original GDTI-ADC. Since the solution is analytical, it is fast, differentiable, and the approximation converges well to the true EAP. This method also makes the effort of computing a positive ADC worthwhile, since now both the ADC and the EAP can be used and have closed forms. We demonstrate our approach with 4th-order tensors on synthetic data and in vivo human data. PMID:23365552

12-bit 32 channel 500 MS/s low-latency ADC for particle accelerators real-time control

NASA Astrophysics Data System (ADS)

Karnitski, Anton; Baranauskas, Dalius; Zelenin, Denis; Baranauskas, Gytis; Zhankevich, Alexander; Gill, Chris

2017-09-01

Particle beam control systems require real-time low latency digital feedback with high linearity and dynamic range. Densely packed electronic systems employ high performance multichannel digitizers causing excessive heat dissipation. Therefore, low power dissipation is another critical requirement for these digitizers. A described 12-bit 500 MS/s ADC employs a sub-ranging architecture based on a merged sample & hold circuit, a residue C-DAC and a shared 6-bit flash core ADC. The core ADC provides a sequential coarse and fine digitization featuring a latency of two clock cycles. The ADC is implemented in a 28 nm CMOS process and consumes 4 mW of power per channel from a 0.9 V supply (interfacing and peripheral circuits are excluded). Reduced power consumption and small on-chip area permits the implementation of 32 ADC channels on a 10.7 mm2 chip. The ADC includes a JESD204B standard compliant output data interface operated at the 7.5 Gbps/ch rate. To minimize the data interface related time latency, a special feature permitting to bypass the JESD204B interface is built in. DoE Phase I Award Number: DE-SC0017213.

The Role of Diffusion-Weighted Magnetic Resonance Imaging in the Differentiation of Head and Neck Masses.

PubMed

Kanmaz, Lutfi; Karavas, Erdal

2018-05-29

The purpose of this study was to evaluate the value of diffusion-weighted MRI (DW-MRI) in differentiating benign and malignant head and neck masses by comparing their apparent diffusion coefficient (ADC) values. The study included 32 patients with a neck mass >1 cm in diameter who were examined with echo planar DW-MRI. Two different diffusion gradients (b values of b = 0 and b = 1000 s/mm²) were applied. DWI and ADC maps of 32 neck masses in 32 patients were obtained. Mean ADC values of benign and malignant neck lesions were measured and compared statistically. A total of 15 (46.9%) malignant masses and 17 (53.1%) benign masses were determined. Of all the neck masses, the ADC value of cystic masses was the highest and that of lymphomas was the lowest. The mean ADC values of benign and malignant neck masses were 1.57 × 10 -3 mm²/s and 0.90 × 10 -3 mm²/s, respectively. The difference between mean ADC values of benign and malignant neck masses was significant ( p < 0.01). Diffusion-weighted MRI with ADC measurements can be useful in the differential diagnosis of neck masses.

Interpolation algorithm for asynchronous ADC-data

NASA Astrophysics Data System (ADS)

Bramburger, Stefan; Zinke, Benny; Killat, Dirk

2017-09-01

This paper presents a modified interpolation algorithm for signals with variable data rate from asynchronous ADCs. The Adaptive weights Conjugate gradient Toeplitz matrix (ACT) algorithm is extended to operate with a continuous data stream. An additional preprocessing of data with constant and linear sections and a weighted overlap of step-by-step into spectral domain transformed signals improve the reconstruction of the asycnhronous ADC signal. The interpolation method can be used if asynchronous ADC data is fed into synchronous digital signal processing.

A CMOS pixel sensor prototype for the outer layers of linear collider vertex detector

NASA Astrophysics Data System (ADS)

Zhang, L.; Morel, F.; Hu-Guo, C.; Himmi, A.; Dorokhov, A.; Hu, Y.

2015-01-01

The International Linear Collider (ILC) expresses a stringent requirement for high precision vertex detectors (VXD). CMOS pixel sensors (CPS) have been considered as an option for the VXD of the International Large Detector (ILD), one of the detector concepts proposed for the ILC. MIMOSA-31 developed at IPHC-Strasbourg is the first CPS integrated with 4-bit column-level ADC for the outer layers of the VXD, adapted to an original concept minimizing the power consumption. It is composed of a matrix of 64 rows and 48 columns. The pixel concept combines in-pixel amplification with a correlated double sampling (CDS) operation in order to reduce the temporal noise and fixed pattern noise (FPN). At the bottom of the pixel array, each column is terminated with a self-triggered analog-to-digital converter (ADC). The ADC design was optimized for power saving at a sampling frequency of 6.25 MS/s. The prototype chip is fabricated in a 0.35 μm CMOS technology. This paper presents the details of the prototype chip and its test results.

Continuous-time ΣΔ ADC with implicit variable gain amplifier for CMOS image sensor.

PubMed

Tang, Fang; Bermak, Amine; Abbes, Amira; Benammar, Mohieddine Amor

2014-01-01

This paper presents a column-parallel continuous-time sigma delta (CTSD) ADC for mega-pixel resolution CMOS image sensor (CIS). The sigma delta modulator is implemented with a 2nd order resistor/capacitor-based loop filter. The first integrator uses a conventional operational transconductance amplifier (OTA), for the concern of a high power noise rejection. The second integrator is realized with a single-ended inverter-based amplifier, instead of a standard OTA. As a result, the power consumption is reduced, without sacrificing the noise performance. Moreover, the variable gain amplifier in the traditional column-parallel read-out circuit is merged into the front-end of the CTSD modulator. By programming the input resistance, the amplitude range of the input current can be tuned with 8 scales, which is equivalent to a traditional 2-bit preamplification function without consuming extra power and chip area. The test chip prototype is fabricated using 0.18 μm CMOS process and the measurement result shows an ADC power consumption lower than 63.5 μW under 1.4 V power supply and 50 MHz clock frequency.

Effect of disease progression on liver apparent diffusion coefficient values in a murine model of NASH at 11.7 Tesla MRI.

PubMed

Anderson, Stephan W; Soto, Jorge A; Milch, Holly N; Ozonoff, Al; O'Brien, Michael; Hamilton, James A; Jara, Hernan J

2011-04-01

To evaluate the apparent diffusion coefficient (ADC) values of liver in a murine model of non-alcoholic steatohepatitis using 11.7 Tesla (T) MRI. This animal study was IACUC approved. Seventeen male C57BL/6 mice were divided into control (n = 3) and experimental groups (n = 14) fed a methionine-deficient choline-deficient (MCD) diet to induce steatohepatitis. Livers underwent ex vivo diffusion-weighted MR imaging and ADC maps were calculated. A pathologist determined subjective scores of steatosis, classified from 0 to 3. Digital image analysis was used to determine percentage areas of steatosis. Graphs comparing ADC to subjective and digital image analysis (DIA) determinations of steatosis were plotted. Subjective assessments of steatosis ranged up to values of 3 and DIA determined areas of steatosis to range up to approximately 16%. ADC values approximated 800 × 10(-6) mm(2) /s (range, 749-811 × 10(-6) mm(2) /s, mean 786 × 10(-6) mm(2) /s) in controls and 500 × 10(-6) mm(2) /s (range, 478-733 × 10(-6) mm(2) /s, mean 625 × 10(-6) mm(2) /s) in experimental mice. Moderate correlation between ADC and subjective scores of steatosis (R = -0.56) was observed. Strong correlation between ADC values and percentage areas of steatosis was between ADC values and percentage areas of steatosis was observed greater (R = -0.81) and very strong correlation was observed with the exclusion of a single outlying data point (R = -0.91). Based on the comparison of ADC values and steatosis determinations by DIA, increasing degrees of steatosis are seen to result in decreased hepatic ADC values. Copyright © 2011 Wiley-Liss, Inc.

Total photoionization cross-sections of excited electronic states by the algebraic diagrammatic construction-Stieltjes-Lanczos method.

PubMed

Ruberti, M; Yun, R; Gokhberg, K; Kopelke, S; Cederbaum, L S; Tarantelli, F; Averbukh, V

2014-05-14

Here, we extend the L2 ab initio method for molecular photoionization cross-sections introduced in Gokhberg et al. [J. Chem. Phys. 130, 064104 (2009)] and benchmarked in Ruberti et al. [J. Chem. Phys. 139, 144107 (2013)] to the calculation of total photoionization cross-sections of molecules in electronically excited states. The method is based on the ab initio description of molecular electronic states within the many-electron Green's function approach, known as algebraic diagrammatic construction (ADC), and on the application of Stieltjes-Chebyshev moment theory to Lanczos pseudospectra of the ADC electronic Hamiltonian. The intermediate state representation of the dipole operator in the ADC basis is used to compute the transition moments between the excited states of the molecule. We compare the results obtained using different levels of the many-body theory, i.e., ADC(1), ADC(2), and ADC(2)x for the first two excited states of CO, N2, and H2O both at the ground state and the excited state equilibrium or saddle point geometries. We find that the single excitation ADC(1) method is not adequate even at the qualitative level and that the inclusion of double electronic excitations for description of excited state photoionization is essential. Moreover, we show that the use of the extended ADC(2)x method leads to a substantial systematic difference from the strictly second-order ADC(2). Our calculations demonstrate that a theoretical modelling of photoionization of excited states requires an intrinsically double excitation theory with respect to the ground state and cannot be achieved by the standard single excitation methods with the ground state as a reference.

Total photoionization cross-sections of excited electronic states by the algebraic diagrammatic construction-Stieltjes-Lanczos method

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

Ruberti, M.; Yun, R.; Averbukh, V.

2014-05-14

Here, we extend the L{sup 2} ab initio method for molecular photoionization cross-sections introduced in Gokhberg et al. [J. Chem. Phys. 130, 064104 (2009)] and benchmarked in Ruberti et al. [J. Chem. Phys. 139, 144107 (2013)] to the calculation of total photoionization cross-sections of molecules in electronically excited states. The method is based on the ab initio description of molecular electronic states within the many-electron Green's function approach, known as algebraic diagrammatic construction (ADC), and on the application of Stieltjes-Chebyshev moment theory to Lanczos pseudospectra of the ADC electronic Hamiltonian. The intermediate state representation of the dipole operator in themore » ADC basis is used to compute the transition moments between the excited states of the molecule. We compare the results obtained using different levels of the many-body theory, i.e., ADC(1), ADC(2), and ADC(2)x for the first two excited states of CO, N{sub 2}, and H{sub 2}O both at the ground state and the excited state equilibrium or saddle point geometries. We find that the single excitation ADC(1) method is not adequate even at the qualitative level and that the inclusion of double electronic excitations for description of excited state photoionization is essential. Moreover, we show that the use of the extended ADC(2)x method leads to a substantial systematic difference from the strictly second-order ADC(2). Our calculations demonstrate that a theoretical modelling of photoionization of excited states requires an intrinsically double excitation theory with respect to the ground state and cannot be achieved by the standard single excitation methods with the ground state as a reference.« less

Value of diffusion-weighted MRI and apparent diffusion coefficient measurements for predicting the response of locally advanced rectal cancer to neoadjuvant chemoradiotherapy.

PubMed

Iannicelli, Elsa; Di Pietropaolo, Marco; Pilozzi, Emanuela; Osti, Mattia Falchetto; Valentino, Maria; Masoni, Luigi; Ferri, Mario

2016-10-01

The aim of our study was to assess the performance value of magnetic resonance imaging (MRI) in the restaging of locally advanced rectal cancer after neoadjuvant chemoradiotherapy (CRT) and in the identification of good vs. poor responders to neoadjuvant therapy. A total of 34 patients with locally advanced rectal cancer underwent MRI prior to and after CRT. T stage and tumor regression grade (TRG) on post-CRT MRI was compared with the pathological staging ypT and TRG. Tumor volume and the apparent diffusion coefficient (ADC) were measured using diffusion-weighted imaging (DWI) before and after neoadjuvant CRT; the percentage of tumor volume reduction and the change of ADC (ΔADC) was also calculated. ADC parameters and the percentage of tumor volume reduction were correlated to histopathological results. The diagnostic performance of ADC and volume reduction to assess tumor response was evaluated by calculating the area under the ROC curve and the optimal cut-off values. A significant correlation between the T stage and the TRG defined in DW-MRI after CRT and the ypT and the TRG observed on the surgical specimens was found (p = 0.001; p < 0.001). The mean post-CRT ADC and ΔADC in responder patients was significantly higher compared to non-responder ones (p = 0.001; p = 0.01). Furthermore, the mean post-CRT ADC values were significantly higher in tumors with T-downstage (p = 0.01). DW-MRI may have a significant role in the restaging and in the evaluation of post-CRT response of locally advanced rectal cancer. Quantitative analysis of DWI through ADC map may result in a promising noninvasive tool to evaluate the response to therapy.

Inter- and intraobserver agreement of ADC measurements of lung cancer in free breathing, breath-hold and respiratory triggered diffusion-weighted MRI.

PubMed

Cui, Lei; Yin, Jian-Bing; Hu, Chun-Hong; Gong, Shen-Chu; Xu, Jun-Feng; Yang, Ju-Shun

2016-01-01

To prospectively evaluate the inter- and intraobserver agreement of apparent diffusion coefficient (ADC) measurements in free breathing, breath-hold, and respiratory triggered diffusion-weighted imaging (DWI) of lung cancer. Twenty-two patients with lung cancer (tumor size >2cm) underwent DWIs (3.0T) in three imaging methods. Lesion ADCs were measured twice by both of the two independent observers and compared. No statistical significance was found among methods, though respiratory-triggered DWI tended to have higher ADCs than breath-hold DWI. Great inter- and intraobserver agreement was shown. ADCs had good inter- and intraobserver agreement in all three DWI methods. Copyright © 2016 Elsevier Inc. All rights reserved.

SALT, a dedicated readout chip for high precision tracking silicon strip detectors at the LHCb Upgrade

NASA Astrophysics Data System (ADS)

Bugiel, Sz.; Dasgupta, R.; Firlej, M.; Fiutowski, T.; Idzik, M.; Kuczynska, M.; Moron, J.; Swientek, K.; Szumlak, T.

2016-02-01

The Upstream Tracker (UT) silicon strip detector, one of the central parts of the tracker system of the modernised LHCb experiment, will use a new 128-channel readout ASIC called SALT. It will extract and digitise analogue signals from the UT sensors, perform digital signal processing and transmit a serial output data. The SALT is being designed in CMOS 130 nm process and uses a novel architecture comprising of analog front-end and fast (40 MSps) ultra-low power (<0.5 mW) 6-bit ADC in each channel. The prototype ASICs of important functional blocks, like analogue front-end, 6-bit SAR ADC, PLL, and DLL, were designed, fabricated and tested. A prototype of an 8-channel version of the SALT chip, comprising all important functionalities was also designed and fabricated. The architecture and design of the SALT, together with the selected preliminary tests results, are presented.

Correlation of 18F-FDG PET and MRI Apparent Diffusion Coefficient Histogram Metrics with Survival in Diffuse Intrinsic Pontine Glioma: A Report from the Pediatric Brain Tumor Consortium.

PubMed

Zukotynski, Katherine A; Vajapeyam, Sridhar; Fahey, Frederic H; Kocak, Mehmet; Brown, Douglas; Ricci, Kelsey I; Onar-Thomas, Arzu; Fouladi, Maryam; Poussaint, Tina Young

2017-08-01

The purpose of this study was to describe baseline 18 F-FDG PET voxel characteristics in pediatric diffuse intrinsic pontine glioma (DIPG) and to correlate these metrics with baseline MRI apparent diffusion coefficient (ADC) histogram metrics, progression-free survival (PFS), and overall survival. Methods: Baseline brain 18 F-FDG PET and MRI scans were obtained in 33 children from Pediatric Brain Tumor Consortium clinical DIPG trials. 18 F-FDG PET images, postgadolinium MR images, and ADC MR images were registered to baseline fluid attenuation inversion recovery MR images. Three-dimensional regions of interest on fluid attenuation inversion recovery MR images and postgadolinium MR images and 18 F-FDG PET and MR ADC histograms were generated. Metrics evaluated included peak number, skewness, and kurtosis. Correlation between PET and MR ADC histogram metrics was evaluated. PET pixel values within the region of interest for each tumor were plotted against MR ADC values. The association of these imaging markers with survival was described. Results: PET histograms were almost always unimodal (94%, vs. 6% bimodal). None of the PET histogram parameters (skewness or kurtosis) had a significant association with PFS, although a higher PET postgadolinium skewness tended toward a less favorable PFS (hazard ratio, 3.48; 95% confidence interval [CI], 0.75-16.28 [ P = 0.11]). There was a significant association between higher MR ADC postgadolinium skewness and shorter PFS (hazard ratio, 2.56; 95% CI, 1.11-5.91 [ P = 0.028]), and there was the suggestion that this also led to shorter overall survival (hazard ratio, 2.18; 95% CI, 0.95-5.04 [ P = 0.067]). Higher MR ADC postgadolinium kurtosis tended toward shorter PFS (hazard ratio, 1.30; 95% CI, 0.98-1.74 [ P = 0.073]). PET and MR ADC pixel values were negatively correlated using the Pearson correlation coefficient. Further, the level of PET and MR ADC correlation was significantly positively associated with PFS; tumors with higher values of ADC-PET correlation had more favorable PFS (hazard ratio, 0.17; 95% CI, 0.03-0.89 [ P = 0.036]), suggesting that a higher level of negative ADC-PET correlation leads to less favorable PFS. A more significant negative correlation may indicate higher-grade elements within the tumor leading to poorer outcomes. Conclusion: 18 F-FDG PET and MR ADC histogram metrics in pediatric DIPG demonstrate different characteristics with often a negative correlation between PET and MR ADC pixel values. A higher negative correlation is associated with a worse PFS, which may indicate higher-grade elements within the tumor. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

Performance of Ultrafast DCE-MRI for Diagnosis of Prostate Cancer.

PubMed

Chatterjee, Aritrick; He, Dianning; Fan, Xiaobing; Wang, Shiyang; Szasz, Teodora; Yousuf, Ambereen; Pineda, Federico; Antic, Tatjana; Mathew, Melvy; Karczmar, Gregory S; Oto, Aytekin

2018-03-01

This study aimed to test high temporal resolution dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) for different zones of the prostate and evaluate its performance in the diagnosis of prostate cancer (PCa). Determine whether the addition of ultrafast DCE-MRI improves the performance of multiparametric MRI. Patients (n = 20) with pathologically confirmed PCa underwent preoperative 3T MRI with T2-weighted, diffusion-weighted, and high temporal resolution (~2.2 seconds) DCE-MRI using gadoterate meglumine (Guerbet, Bloomington, IN) without an endorectal coil. DCE-MRI data were analyzed by fitting signal intensity with an empirical mathematical model to obtain parameters: percent signal enhancement, enhancement rate (α), washout rate (β), initial enhancement slope, and enhancement start time along with apparent diffusion coefficient (ADC) and T2 values. Regions of interests were placed on sites of prostatectomy verified malignancy (n = 46) and normal tissue (n = 71) from different zones. Cancer (α = 6.45 ± 4.71 s -1 , β = 0.067 ± 0.042 s -1 , slope = 3.78 ± 1.90 s -1 ) showed significantly (P <.05) faster signal enhancement and washout rates than normal tissue (α = 3.0 ± 2.1 s -1 , β = 0.034 ± 0.050 s -1 , slope = 1.9 ± 1.4 s -1 ), but showed similar percentage signal enhancement and enhancement start time. Receiver operating characteristic analysis showed area under the curve for DCE parameters was comparable to ADC and T2 in the peripheral (DCE 0.67-0.82, ADC 0.80, T2 0.89) and transition zones (DCE 0.61-0.72, ADC 0.69, T2 0.75), but higher in the central zone (DCE 0.79-0.88, ADC 0.45, T2 0.45) and anterior fibromuscular stroma (DCE 0.86-0.89, ADC 0.35, T2 0.12). Importantly, combining DCE with ADC and T2 increased area under the curve by ~30%, further improving the diagnostic accuracy of PCa detection. Quantitative parameters from empirical mathematical model fits to ultrafast DCE-MRI improve diagnosis of PCa. DCE-MRI with higher temporal resolution may capture clinically useful information for PCa diagnosis that would be missed by low temporal resolution DCE-MRI. This new information could improve the performance of multiparametric MRI in PCa detection. Copyright © 2018 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.

The Spatial Relationship between Apparent Diffusion Coefficient and Standardized Uptake Value of 18F-Fluorodeoxyglucose Has a Crucial Influence on the Numeric Correlation of Both Parameters in PET/MRI of Lung Tumors.

PubMed

Sauter, Alexander W; Stieltjes, Bram; Weikert, Thomas; Gatidis, Sergios; Wiese, Mark; Klarhöfer, Markus; Wild, Damian; Lardinois, Didier; Bremerich, Jens; Sommer, Gregor

2017-01-01

The minimum apparent diffusion coefficient (ADC min ) derived from diffusion-weighted MRI (DW-MRI) and the maximum standardized uptake value (SUV max ) of FDG-PET are markers of aggressiveness in lung cancer. The numeric correlation of the two parameters has been extensively studied, but their spatial interplay is not well understood. After FDG-PET and DW-MRI coregistration, values and location of ADC min - and SUV max -voxels were analyzed. The upper limit of the 95% confidence interval for registration accuracy of sequential PET/MRI was 12 mm, and the mean distance ( D ) between ADC min - and SUV max -voxels was 14.0 mm (average of two readers). Spatial mismatch ( D > 12 mm) between ADC min and SUV max was found in 9/25 patients. A considerable number of mismatch cases (65%) was also seen in a control group that underwent simultaneous PET/MRI. In the entire patient cohort, no statistically significant correlation between SUV max and ADC min was seen, while a moderate negative linear relationship ( r = -0.5) between SUV max and ADC min was observed in tumors with a spatial match ( D ≤ 12 mm). In conclusion, spatial mismatch between ADC min and SUV max is found in a considerable percentage of patients. The spatial connection of the two parameters SUV max and ADC min has a crucial influence on their numeric correlation.

Multivalent peptidic linker enables identification of preferred sites of conjugation for a potent thialanstatin antibody drug conjugate.

PubMed

Puthenveetil, Sujiet; He, Haiyin; Loganzo, Frank; Musto, Sylvia; Teske, Jesse; Green, Michael; Tan, Xingzhi; Hosselet, Christine; Lucas, Judy; Tumey, L Nathan; Sapra, Puja; Subramanyam, Chakrapani; O'Donnell, Christopher J; Graziani, Edmund I

2017-01-01

Antibody drug conjugates (ADCs) are no longer an unknown entity in the field of cancer therapy with the success of marketed ADCs like ADCETRIS and KADCYLA and numerous others advancing through clinical trials. The pursuit of novel cytotoxic payloads beyond the mictotubule inhibitors and DNA damaging agents has led us to the recent discovery of an mRNA splicing inhibitor, thailanstatin, as a potent ADC payload. In our previous work, we observed that the potency of this payload was uniquely tied to the method of conjugation, with lysine conjugates showing much superior potency as compared to cysteine conjugates. However, the ADC field is rapidly shifting towards site-specific ADCs due to their advantages in manufacturability, characterization and safety. In this work we report the identification of a highly efficacious site-specific thailanstatin ADC. The site of conjugation played a critical role on both the in vitro and in vivo potency of these ADCs. During the course of this study, we developed a novel methodology of loading a single site with multiple payloads using an in situ generated multi-drug carrying peptidic linker that allowed us to rapidly screen for optimal conjugation sites. Using this methodology, we were able to identify a double-cysteine mutant ADC delivering four-loaded thailanstatin that was very efficacious in a gastric cancer xenograft model at 3mg/kg and was also shown to be efficacious against T-DM1 resistant and MDR1 overexpressing tumor cell lines.

Antibody-Drug Conjugates (ADCs) for Personalized Treatment of Solid Tumors: A Review.

PubMed

Lambert, John M; Morris, Charles Q

2017-05-01

Attaching a cytotoxic "payload" to an antibody to form an antibody-drug conjugate (ADC) provides a mechanism for selective delivery of the cytotoxic agent to cancer cells via the specific binding of the antibody to cancer-selective cell surface molecules. The first ADC to receive marketing authorization was gemtuzumab ozogamicin, which comprises an anti-CD33 antibody conjugated to a highly potent DNA-targeting antibiotic, calicheamicin, approved in 2000 for treating acute myeloid leukemia. It was withdrawn from the US market in 2010 following an unsuccessful confirmatory trial. The development of two classes of highly potent microtubule-disrupting agents, maytansinoids and auristatins, as payloads for ADCs resulted in approval of brentuximab vedotin in 2011 for treating Hodgkin lymphoma and anaplastic large cell lymphoma, and approval of ado-trastuzumab emtansine in 2013 for treating HER2-positive breast cancer. Their success stimulated much research into the ADC approach, with >60 ADCs currently in clinical evaluation, mostly targeting solid tumors. Five ADCs have advanced into pivotal clinical trials for treating various solid tumors-platinum-resistant ovarian cancer, mesothelioma, triple-negative breast cancer, glioblastoma, and small cell lung cancer. The level of target expression is a key parameter in predicting the likelihood of patient benefit for all these ADCs, as well as for the approved compound, ado-trastuzumab emtansine. The development of a patient selection strategy linked to target expression on the tumor is thus critically important for identifying the population appropriate for receiving treatment.

Sodium-23 magnetic resonance imaging has potential for improving penumbra detection but not for estimating stroke onset time

PubMed Central

Wetterling, Friedrich; Gallagher, Lindsay; Mullin, Jim; Holmes, William M; McCabe, Chris; Macrae, I Mhairi; Fagan, Andrew J

2015-01-01

Tissue sodium concentration increases in irreversibly damaged (core) tissue following ischemic stroke and can potentially help to differentiate the core from the adjacent hypoperfused but viable penumbra. To test this, multinuclear hydrogen-1/sodium-23 magnetic resonance imaging (MRI) was used to measure the changing sodium signal and hydrogen-apparent diffusion coefficient (ADC) in the ischemic core and penumbra after rat middle cerebral artery occlusion (MCAO). Penumbra and core were defined from perfusion imaging and histologically defined irreversibly damaged tissue. The sodium signal in the core increased linearly with time, whereas the ADC rapidly decreased by >30% within 20 minutes of stroke onset, with very little change thereafter (0.5–6 hours after MCAO). Previous reports suggest that the time point at which tissue sodium signal starts to rise above normal (onset of elevated tissue sodium, OETS) represents stroke onset time (SOT). However, extrapolating core data back in time resulted in a delay of 72±24 minutes in OETS compared with actual SOT. At the OETS in the core, penumbra sodium signal was significantly decreased (88±6%, P=0.0008), whereas penumbra ADC was not significantly different (92±18%, P=0.2) from contralateral tissue. In conclusion, reduced sodium-MRI signal may serve as a viability marker for penumbra detection and can complement hydrogen ADC and perfusion MRI in the time-independent assessment of tissue fate in acute stroke patients. PMID:25335803

The distribution of the apparent diffusion coefficient as an indicator of the response to chemotherapeutics in ovarian tumour xenografts

NASA Astrophysics Data System (ADS)

Tourell, Monique C.; Shokoohmand, Ali; Landgraf, Marietta; Holzapfel, Nina P.; Poh, Patrina S. P.; Loessner, Daniela; Momot, Konstantin I.

2017-02-01

Diffusion-weighted magnetic resonance imaging (DW-MRI) was used to evaluate the effects of single-agent and combination treatment regimens in a spheroid-based animal model of ovarian cancer. Ovarian tumour xenografts grown in non-obese diabetic/severe-combined-immunodeficiency (NOD/SCID) mice were treated with carboplatin or paclitaxel, or combination carboplatin/paclitaxel chemotherapy regimens. After 4 weeks of treatment, tumours were extracted and underwent DW-MRI, mechanical testing, immunohistochemical and gene expression analyses. The distribution of the apparent diffusion coefficient (ADC) exhibited an upward shift as a result of each treatment regimen. The 99-th percentile of the ADC distribution (“maximum ADC”) exhibited a strong correlation with the tumour size (r2 = 0.90) and with the inverse of the elastic modulus (r2 = 0.96). Single-agent paclitaxel (n = 5) and combination carboplatin/paclitaxel (n = 2) treatment regimens were more effective in inducing changes in regions of higher cell density than single-agent carboplatin (n = 3) or the no-treatment control (n = 5). The maximum ADC was a good indicator of treatment-induced cell death and changes in the extracellular matrix (ECM). Comparative analysis of the tumours’ ADC distribution, mechanical properties and ECM constituents provides insights into the molecular and cellular response of the ovarian tumour xenografts to chemotherapy. Increased sample sizes are recommended for future studies. We propose experimental approaches to evaluation of the timeline of the tumour’s response to treatment.

Central acylated ghrelin improves memory function and hippocampal AMPK activation and partly reverses the impairment of energy and glucose metabolism in rats infused with β-amyloid.

PubMed

Kang, Suna; Moon, Na Rang; Kim, Da Sol; Kim, Sung Hoon; Park, Sunmin

2015-09-01

Ghrelin is a gastric hormone released during the fasting state that targets the hypothalamus where it induces hunger; however, emerging evidence suggests it may also affect memory function. We examined the effect of central acylated-ghrelin and DES-acetylated ghrelin (native ghrelin) on memory function and glucose metabolism in an experimentally induced Alzheimer's disease (AD) rat model. AD rats were divided into 3 groups and Non-AD rats were used as a normal-control group. Each rat in the AD groups had intracerebroventricular (ICV) infusion of β-amyloid (25-35; 16.8nmol/day) into the lateral ventricle for 3 days, and then the pumps were changed to infuse either acylated-ghrelin (0.2nmol/h; AD-G), DES-acylated ghrelin (0.2nmol/h; AD-DES-G), or saline (control; AD-C) for 3 weeks. The Non-AD group had ICV infusion of β-amyloid (35-25) which does not deposit in the hippocampus. During the next 3 weeks memory function, food intake, body weight gain, body fat composition, and glucose metabolism were measured. AD-C exhibited greater β-amyloid deposition compared to Non-AD-C, and AD-G suppressed the increased β-amyloid deposition and potentiated the phosphorylation AMPK. In addition, AD-G increased the phosphorylation GSK and decreased the phosphorylation of Tau in comparison to AD-C and AD-DES-G. Cognitive function, measured by passive avoidance and water maze tests, was much lower in AD-C than Non-AD-C whereas AD-G but not AD-DES-G prevented the decrease (p<0.021). Body weight gain was lower in AD-C group than Non-AD-C group without changing epididymal fat mass. AD-G reversed the decrease in body weight which was due to increased energy intake and decreased energy expenditure. The AD-G group exhibited a decrease in the second part of serum glucose levels during an oral glucose tolerance test (OGTT) compared to the AD-C and AD-DES-G group (p<0.009). However, area under the curve of insulin during the first part of OGTT was higher in AD-DES-G than other groups, whereas during the second part it was suppressed in AD-G as much as Non-AD. In conclusion, central acylated ghrelin in rats prevented the deterioration of memory function, and energy and glucose metabolisms were partially improved, possibly due to less β-amyloid accumulation. This research suggests that interventions such as intermittent fasting to facilitate sustained elevations of acyl-ghrelin should be investigated for cognitive and metabolic benefits, especially in person with early symptoms of memory impairment. Copyright © 2015 Elsevier Inc. All rights reserved.

Self-Calibration Approach for Mixed Signal Circuits in Systems-on-Chip

NASA Astrophysics Data System (ADS)

Jung, In-Seok

MOSFET scaling has served industry very well for a few decades by proving improvements in transistor performance, power, and cost. However, they require high test complexity and cost due to several issues such as limited pin count and integration of analog and digital mixed circuits. Therefore, self-calibration is an excellent and promising method to improve yield and to reduce manufacturing cost by simplifying the test complexity, because it is possible to address the process variation effects by means of self-calibration technique. Since the prior published calibration techniques were developed for a specific targeted application, it is not easy to be utilized for other applications. In order to solve the aforementioned issues, in this dissertation, several novel self-calibration design techniques in mixed-signal mode circuits are proposed for an analog to digital converter (ADC) to reduce mismatch error and improve performance. These are essential components in SOCs and the proposed self-calibration approach also compensates the process variations. The proposed novel self-calibration approach targets the successive approximation (SA) ADC. First of all, the offset error of the comparator in the SA-ADC is reduced using the proposed approach by enabling the capacitor array in the input nodes for better matching. In addition, the auxiliary capacitors for each capacitor of DAC in the SA-ADC are controlled by using synthesized digital controller to minimize the mismatch error of the DAC. Since the proposed technique is applied during foreground operation, the power overhead in SA-ADC case is minimal because the calibration circuit is deactivated during normal operation time. Another benefit of the proposed technique is that the offset voltage of the comparator is continuously adjusted for every step to decide one-bit code, because not only the inherit offset voltage of the comparator but also the mismatch of DAC are compensated simultaneously. Synthesized digital calibration control circuit operates as fore-ground mode, and the controller has been highly optimized for low power and better performance with simplified structure. In addition, in order to increase the sampling clock frequency of proposed self-calibration approach, novel variable clock period method is proposed. To achieve high speed SAR operation, a variable clock time technique is used to reduce not only peak current but also die area. The technique removes conversion time waste and extends the SAR operation speed easily. To verify and demonstrate the proposed techniques, a prototype charge-redistribution SA-ADCs with the proposed self-calibration is implemented in a 130nm standard CMOS process. The prototype circuit's silicon area is 0.0715 mm 2 and consumers 4.62mW with 1.2V power supply.

ANALOG I/O MODULE TEST SYSTEM BASED ON EPICS CA PROTOCOL AND ACTIVEX CA INTERFACE

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

YENG,YHOFF,L.

2003-10-13

Analog input (ADC) and output (DAC) modules play a substantial role in device level control of accelerator and large experiment physics control system. In order to get the best performance some features of analog modules including linearity, accuracy, crosstalk, thermal drift and so on have to be evaluated during the preliminary design phase. Gain and offset error calibration and thermal drift compensation (if needed) may have to be done in the implementation phase as well. A natural technique for performing these tasks is to interface the analog VO modules and GPIB interface programmable test instruments with a computer, which canmore » complete measurements or calibration automatically. A difficulty is that drivers of analog modules and test instruments usually work on totally different platforms (vxworks VS Windows). Developing new test routines and drivers for testing instruments under VxWorks (or any other RTOS) platform is not a good solution because such systems have relatively poor user interface and developing such software requires substantial effort. EPICS CA protocol and ActiveX CA interface provide another choice, a PC and LabVIEW based test system. Analog 110 module can be interfaced from LabVIEW test routines via ActiveX CA interface. Test instruments can be controlled via LabVIEW drivers, most of which are provided by instrument vendors or by National Instruments. Labview also provides extensive data analysis and process functions. Using these functions, users can generate powerful test routines very easily. Several applications built for Spallation Neutron Source (SNS) Beam Loss Monitor (BLM) system are described in this paper.« less

High power-efficient asynchronous SAR ADC for IoT devices

NASA Astrophysics Data System (ADS)

Zhang, Beichen; Yao, Bingbing; Liu, Liyuan; Liu, Jian; Wu, Nanjian

2017-10-01

This paper presents a power-efficient 100-MS/s, 10-bit asynchronous successive approximation register (SAR) ADC. It includes an on-chip reference buffer and the total power dissipation is 6.8 mW. To achieve high performance with high power-efficiency in the proposed ADC, bootstrapped switch, redundancy, set-and-down switching approach, dynamic comparator and dynamic logic techniques are employed. The prototype was fabricated using 65 nm standard CMOS technology. At a 1.2-V supply and 100 MS/s, the ADC achieves an SNDR of 56.2 dB and a SFDR of 65.1 dB. The ADC core consumes only 3.1 mW, resulting in a figure of merit (FOM) of 30.27 fJ/conversionstep and occupies an active area of only 0.009 mm2.

Resistance to Antibody-Drug Conjugates.

PubMed

García-Alonso, Sara; Ocaña, Alberto; Pandiella, Atanasio

2018-05-01

Antibody-drug conjugates (ADC) are multicomponent molecules constituted by an antibody covalently linked to a potent cytotoxic agent. ADCs combine high target specificity provided by the antibody together with strong antitumoral properties provided by the attached cytotoxic agent. At present, four ADCs have been approved and over 60 are being explored in clinical trials. Despite their effectiveness, resistance to these drugs unfortunately occurs. Efforts to understand the bases underlying such resistance are being carried out with the final purpose of counteracting them. In this review, we report described mechanisms of resistance to ADCs used in the clinic along with other potential ones that may contribute to resistance acquisition. We also discuss strategies to overcome resistance to ADCs. Cancer Res; 78(9); 2159-65. ©2018 AACR . ©2018 American Association for Cancer Research.

Intracellular trafficking of new anticancer therapeutics: antibody-drug conjugates.

PubMed

Kalim, Muhammad; Chen, Jie; Wang, Shenghao; Lin, Caiyao; Ullah, Saif; Liang, Keying; Ding, Qian; Chen, Shuqing; Zhan, Jinbiao

2017-01-01

Antibody-drug conjugate (ADC) is a milestone in targeted cancer therapy that comprises of monoclonal antibodies chemically linked to cytotoxic drugs. Internalization of ADC takes place via clathrin-mediated endocytosis, caveolae-mediated endocytosis, and pinocytosis. Conjugation strategies, endocytosis and intracellular trafficking optimization, linkers, and drugs chemistry present a great challenge for researchers to eradicate tumor cells successfully. This inventiveness of endocytosis and intracellular trafficking has given considerable momentum recently to develop specific antibodies and ADCs to treat cancer cells. It is significantly advantageous to emphasize the endocytosis and intracellular trafficking pathways efficiently and to design potent engineered conjugates and biological entities to boost efficient therapies enormously for cancer treatment. Current studies illustrate endocytosis and intracellular trafficking of ADC, protein, and linker strategies in unloading and also concisely evaluate practically applicable ADCs.

Intracellular trafficking of new anticancer therapeutics: antibody–drug conjugates

PubMed Central

Kalim, Muhammad; Chen, Jie; Wang, Shenghao; Lin, Caiyao; Ullah, Saif; Liang, Keying; Ding, Qian; Chen, Shuqing; Zhan, Jinbiao

2017-01-01

Antibody–drug conjugate (ADC) is a milestone in targeted cancer therapy that comprises of monoclonal antibodies chemically linked to cytotoxic drugs. Internalization of ADC takes place via clathrin-mediated endocytosis, caveolae-mediated endocytosis, and pinocytosis. Conjugation strategies, endocytosis and intracellular trafficking optimization, linkers, and drugs chemistry present a great challenge for researchers to eradicate tumor cells successfully. This inventiveness of endocytosis and intracellular trafficking has given considerable momentum recently to develop specific antibodies and ADCs to treat cancer cells. It is significantly advantageous to emphasize the endocytosis and intracellular trafficking pathways efficiently and to design potent engineered conjugates and biological entities to boost efficient therapies enormously for cancer treatment. Current studies illustrate endocytosis and intracellular trafficking of ADC, protein, and linker strategies in unloading and also concisely evaluate practically applicable ADCs. PMID:28814834

Random Walk Simulation of the MRI Apparent Diffusion Coefficient in a Geometrical Model of the Acinar Tree

PubMed Central

Pérez-Sánchez, José M.; Rodríguez, Ignacio; Ruiz-Cabello, Jesús

2009-01-01

Abstract Apparent diffusion coefficient (ADC) measurement in the lung using gas magnetic resonance imaging is a promising technique with potential for reflecting changes in lung microstructure. Despite some recent impressive human applications, full interpretation of ADC measures remains an elusive goal, due to a lack of detailed knowledge about the structure dependency of ADC. In an attempt to fill this gap we have performed random walk simulations in a three-dimensional geometrical model of the lung acinus, the distal alveolated sections of the lung tree accounting for ∼90% of the total lung volume. Simulations were carried out adjusting model parameters after published morphological data for the rat peripheral airway system, which predict an ADC behavior as microstructure changes with lung inflation in partial agreement with measured ADCs at different airway pressures. The approach used to relate experimental ADCs to lung microstructural changes does not make any assumption about the cause of the changes, so it could be applied to other scenarios such as chronic obstructive pulmonary disease, lung development, etc. The work presented here predicts numerically for the first time ADC values measured in the lung from independent morphological measures of lung microstructure taken at different inflation stages during the breath cycle. PMID:19619480

Histogram analysis parameters of apparent diffusion coefficient reflect tumor cellularity and proliferation activity in head and neck squamous cell carcinoma

PubMed Central

Winter, Karsten; Richter, Cindy; Hoehn, Anna-Kathrin

2018-01-01

Our purpose was to analyze associations between apparent diffusion coefficient (ADC) histogram analysis parameters and histopathologicalfeatures in head and neck squamous cell carcinoma (HNSCC). The study involved 32 patients with primary HNSCC. For every tumor, the following histogram analysis parameters were calculated: ADCmean, ADCmax, ADCmin, ADCmedian, ADCmode, P10, P25, P75, P90, kurtosis, skewness, and entropy. Furthermore, proliferation index KI 67, cell count, total and average nucleic areas were estimated. Spearman's correlation coefficient (p) was used to analyze associations between investigated parameters. In overall sample, all ADC values showed moderate inverse correlations with KI 67. All ADC values except ADCmax correlated inversely with tumor cellularity. Slightly correlations were identified between total/average nucleic area and ADCmean, ADCmin, ADCmedian, and P25. In G1/2 tumors, only ADCmode correlated well with Ki67. No statistically significant correlations between ADC parameters and cellularity were found. In G3 tumors, Ki 67 correlated with all ADC parameters except ADCmode. Cell count correlated well with all ADC parameters except ADCmax. Total nucleic area correlated inversely with ADCmean, ADCmin, ADCmedian, P25, and P90. ADC histogram parameters reflect proliferation potential and cellularity in HNSCC. The associations between histopathology and imaging depend on tumor grading. PMID:29805759

Hyperpolarized 3He and 129Xe magnetic resonance imaging apparent diffusion coefficients: physiological relevance in older never‐ and ex‐smokers

PubMed Central

Kirby, Miranda; Ouriadov, Alexei; Svenningsen, Sarah; Owrangi, Amir; Wheatley, Andrew; Etemad‐Rezai, Roya; Santyr, Giles E.; McCormack, David G.; Parraga, Grace

2014-01-01

Abstract Noble gas pulmonary magnetic resonance imaging (MRI) is transitioning away from 3He to 129Xe gas, but the physiological/clinical relevance of 129Xe apparent diffusion coefficient (ADC) parenchyma measurements is not well understood. Therefore, our objective was to generate 129Xe MRI ADC for comparison with 3He ADC and with well‐established measurements of alveolar structure and function in older never‐smokers and ex‐smokers with chronic obstructive pulmonary disease (COPD). In four never‐smokers and 10 COPD ex‐smokers, 3He (b = 1.6 sec/cm2) and 129Xe (b = 12, 20, and 30 sec/cm2) ADC, computed tomography (CT) density‐threshold measurements, and the diffusing capacity for carbon monoxide (DLCO) were measured. To understand regional differences, the anterior–posterior (APG) and superior–inferior (∆SI) ADC differences were evaluated. Compared to never‐smokers, COPD ex‐smokers showed greater 3He ADC (P = 0.006), 129Xe ADCb12 (P = 0.006), and ADCb20 (P = 0.006), but not for ADCb30 (P > 0.05). Never‐smokers and COPD ex‐smokers had significantly different APG for 3He ADC (P = 0.02), 129Xe ADCb12 (P = 0.006), and ADCb20 (P = 0.01), but not for ADCb30 (P > 0.05). ∆SI for never‐ and ex‐smokers was significantly different for 3He ADC (P = 0.046), but not for 129Xe ADC (P > 0.05). There were strong correlations for DLCO with 3He ADC and 129Xe ADCb12 (both r = −0.95, P < 0.05); in a multivariate model 129Xe ADCb12 was the only significant predictor of DLCO (P = 0.049). For COPD ex‐smokers, CT relative area <−950 HU (RA950) correlated with 3He ADC (r = 0.90, P = 0.008) and 129Xe ADCb12 (r = 0.85, P = 0.03). In conclusion, while 129Xe ADCb30 may be appropriate for evaluating subclinical or mild emphysema, in this small group of never‐smokers and ex‐smokers with moderate‐to‐severe emphysema, 129Xe ADCb12 provided a physiologically appropriate estimate of gas exchange abnormalities and alveolar microstructure. PMID:25347853

A Digital Motion Control System for Large Telescopes

NASA Astrophysics Data System (ADS)

Hunter, T. R.; Wilson, R. W.; Kimberk, R.; Leiker, P. S.

2001-05-01

We have designed and programmed a digital motion control system for large telescopes, in particular, the 6-meter antennas of the Submillimeter Array on Mauna Kea. The system consists of a single robust, high-reliability microcontroller board which implements a two-axis velocity servo while monitoring and responding to critical safety parameters. Excellent tracking performance has been achieved with this system (0.3 arcsecond RMS at sidereal rate). The 24x24 centimeter four-layer printed circuit board contains a multitude of hardware devices: 40 digital inputs (for limit switches and fault indicators), 32 digital outputs (to enable/disable motor amplifiers and brakes), a quad 22-bit ADC (to read the motor tachometers), four 16-bit DACs (that provide torque signals to the motor amplifiers), a 32-LED status panel, a serial port to the LynxOS PowerPC antenna computer (RS422/460kbps), a serial port to the Palm Vx handpaddle (RS232/115kbps), and serial links to the low-resolution absolute encoders on the azimuth and elevation axes. Each section of the board employs independent ground planes and power supplies, with optical isolation on all I/O channels. The processor is an Intel 80C196KC 16-bit microcontroller running at 20MHz on an 8-bit bus. This processor executes an interrupt-driven, scheduler-based software system written in C and assembled into an EPROM with user-accessible variables stored in NVSRAM. Under normal operation, velocity update requests arrive at 100Hz from the position-loop servo process running independently on the antenna computer. A variety of telescope safety checks are performed at 279Hz including routine servicing of a 6 millisecond watchdog timer. Additional ADCs onboard the microcontroller monitor the winding temperature and current in the brushless three-phase drive motors. The PID servo gains can be dynamically changed in software. Calibration factors and software filters can be applied to the tachometer readings prior to the application of the servo gains in the torque computations. The Palm pilot handpaddle displays the complete status of the telescope and allows full local control of the drives in an intuitive, touchscreen user interface which is especially useful during reconfigurations of the antenna array.

Identification of early and distinct glioblastoma response patterns treated by boron neutron capture therapy not predicted by standard radiographic assessment using functional diffusion map

PubMed Central

2013-01-01

Background Radiologic response of brain tumors is traditionally assessed according to the Macdonald criteria 10 weeks from the start of therapy. Because glioblastoma (GB) responds in days rather than weeks after boron neutron capture therapy (BNCT) that is a form of tumor-selective particle radiation, it is inconvenient to use the Macdonald criteria to assess the therapeutic efficacy of BNCT by gadolinium-magnetic resonance imaging (Gd-MRI). Our study assessed the utility of functional diffusion map (fDM) for evaluating response patterns in GB treated by BNCT. Methods The fDM is an image assessment using time-dependent changes of apparent diffusion coefficient (ADC) in tumors on a voxel-by-voxel approach. Other than time-dependent changes of ADC, fDM can automatically assess minimum/maximum ADC, Response Evaluation Criteria In Solid Tumors (RECIST), and the volume of enhanced lesions on Gd-MRI over time. We assessed 17 GB patients treated by BNCT using fDM. Additionally, in order to verify our results, we performed a histopathological examination using F98 rat glioma models. Results Only the volume of tumor with decreased ADC by fDM at 2 days after BNCT was a good predictor for GB patients treated by BNCT (P value = 0.022 by log-rank test and 0.033 by wilcoxon test). In a histopathological examination, brain sections of F98 rat glioma models treated by BNCT showed cell swelling of both the nuclei and the cytoplasm compared with untreated rat glioma models. Conclusions The fDM could identify response patterns in BNCT-treated GB earlier than a standard radiographic assessment. Early detection of treatment failure can allow a change or supplementation before tumor progression and might lead to an improvement of GB patients’ prognosis. PMID:23915330

On-field measurement trial of 4×128 Gbps PDM-QPSK signals by linear optical sampling

NASA Astrophysics Data System (ADS)

Bin Liu; Wu, Zhichao; Fu, Songnian; Feng, Yonghua; Liu, Deming

2017-02-01

Linear optical sampling is a promising characterization technique for advanced modulation formats, together with digital signal processing (DSP) and software-synchronized algorithm. We theoretically investigate the acquisition of optical sampling, when the high-speed signal under test is either periodic or random. Especially, when the profile of optical sampling pulse is asymmetrical, the repetition frequency of sampling pulse needs careful adjustment in order to obtain correct waveform. Then, we demonstrate on-field measurement trial of commercial four-channel 128 Gbps polarization division multiplexing quadrature phase shift keying (PDM-QPSK) signals with truly random characteristics by self-developed equipment. A passively mode-locked fiber laser (PMFL) with a repetition frequency of 95.984 MHz is used as optical sampling source, meanwhile four balanced photo detectors (BPDs) with 400 MHz bandwidth and four-channel analog-to-digital convertor (ADC) with 1.25 GS/s sampling rate are used for data acquisition. The performance comparison with conventional optical modulation analyzer (OMA) verifies that the self-developed equipment has the advantages of low cost, easy implementation, and fast response.

Predicting Treatment Response of Colorectal Cancer Liver Metastases to Conventional Lipiodol-Based Transarterial Chemoembolization Using Diffusion-Weighted MR Imaging: Value of Pretreatment Apparent Diffusion Coefficients (ADC) and ADC Changes Under Therapy

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

Lahrsow, Maximilian, E-mail: mlahrsow@gmail.com; Albrecht, Moritz H.; Bickford, Matthew W.

PurposeTo use absolute pretreatment apparent diffusion coefficients (ADC) derived from diffusion-weighted MR imaging (DWI) to predict response to repetitive cTACE for unresectable liver metastases of colorectal carcinoma (CRLM) at 1 and 3 months after start of treatment.Materials and MethodsFifty-five metastases in 34 patients were examined with DWI prior to treatment and 1 month after initial cTACE. Treatment was performed in 4-week intervals. Response was evaluated at 1 and 3 months after start of therapy. Metastases showing a decrease of ≥30% in axial diameter were classified as responding lesions.ResultsOne month after initial cTACE, seven lesions showed early response. There was no significant differencemore » in absolute pretreatment ADC values between responding and non-responding lesions (p = 0.94). Three months after initial cTACE, 17 metastases showed response. There was a significant difference (p = 0.021) between absolute pretreatment ADC values of lesions showing response (median 1.08 × 10{sup −3} mm{sup 2}/s) and no response (median 1.30 × 10{sup −3} mm{sup 2}/s). Pretreatment ADC showed fair diagnostic value to predict response (AUC 0.7). Lesions showing response at 3 months also revealed a significant increase in ADC between measurements before treatment and at one month after initial cTACE (p < 0.001). Applying an increase in ADC of 12.17%, response at 3 months after initial cTACE could be predicted with a sensitivity and specificity of 77 and 74%, respectively (AUC 0.817). Furthermore, there was a strong and significant correlation (r = 0.651, p < 0.001) between percentage change in size after third cTACE and percentage change in ADC.ConclusionIn patients with CRLM, ADC measurements are potential biomarkers for assessing response to cTACE.« less

Whole-lesion histogram analysis of the apparent diffusion coefficient: Evaluation of the correlation with subtypes of mucinous breast carcinoma.

PubMed

Guo, Yuan; Kong, Qing-Cong; Zhu, Ye-Qing; Liu, Zhen-Zhen; Peng, Ling-Rong; Tang, Wen-Jie; Yang, Rui-Meng; Xie, Jia-Jun; Liu, Chun-Ling

2018-02-01

To evaluate the utility of the whole-lesion histogram apparent diffusion coefficient (ADC) for characterizing the heterogeneity of mucinous breast carcinoma (MBC) and to determine which ADC metrics may help to best differentiate subtypes of MBC. This retrospective study involved 52 MBC patients, including 37 pure MBC (PMBC) and 15 mixed MBC (MMBC). The PMBC patients were subtyped into PMBC-A (20 cases) and PMBC-B (17 cases) groups. All patients underwent preoperative diffusion-weighted imaging (DWI) at 1.5T and the whole-lesion ADC assessments were generated. Histogram-derived ADC parameters were compared between PMBC vs. MMBC and PMBC-A vs. PMBC-B, and receiver operating characteristic (ROC) curve analysis was used to determine optimal histogram parameters for differentiating these groups. The PMBC group exhibited significantly higher ADC values for the mean (P = 0.004), 25 th (P = 0.004), 50 th (P = 0.004), 75 th (P = 0.006), and 90 th percentiles (P = 0.013) and skewness (P = 0.021) than did the MMBC group. The 25 th percentile of ADC values achieved the highest area under the curve (AUC) (0.792), with a cutoff value of 1.345 × 10 -3 mm 2 /s, in distinguishing PMBC and MMBC. The PMBC-A group showed significantly higher ADC values for the mean (P = 0.049), 25 th (P = 0.015), and 50 th (P = 0.026) percentiles and skewness (P = 0.004) than did the PMBC-B group. The 25 th percentile of the ADC cutoff value (1.476 × 10 -3 mm 2 /s) demonstrated the best AUC (0.837) among the ADC values for distinguishing PMBC-A and PMBC-B. Whole-lesion ADC histogram analysis enables comprehensive evaluation of an MBC in its entirety and differentiating subtypes of MBC. Thus, it may be a helpful and supportive tool for conventional MRI. 4 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;47:391-400. © 2017 International Society for Magnetic Resonance in Medicine.

DCE-MRI-Derived Volume Transfer Constant (Ktrans) and DWI Apparent Diffusion Coefficient as Predictive Markers of Short- and Long-Term Efficacy of Chemoradiotherapy in Patients With Esophageal Cancer.

PubMed

Ye, Zhi-Min; Dai, Shu-Jun; Yan, Feng-Qin; Wang, Lei; Fang, Jun; Fu, Zhen-Fu; Wang, Yue-Zhen

2018-01-01

This study aimed to evaluate both the short- and long-term efficacies of chemoradiotherapy in relation to the treatment of esophageal cancer . This was achieved through the use of dynamic contrast-enhanced magnetic resonance imaging-derived volume transfer constant and diffusion weighted imaging-derived apparent diffusion coefficient . Patients with esophageal cancer were assigned into the sensitive and resistant groups based on respective efficacies in chemoradiotherapy. Dynamic contrast-enhanced magnetic resonance imaging and diffusion weighted imaging were used to measure volume transfer constant and apparent diffusion coefficient, while computed tomography was used to calculate tumor size reduction rate. Pearson correlation analyses were conducted to analyze correlation between volume transfer constant, apparent diffusion coefficient, and the tumor size reduction rate. Receiver operating characteristic curve was constructed to analyze the short-term efficacy of volume transfer constant and apparent diffusion coefficient, while Kaplan-Meier curve was employed for survival rate analysis. Cox proportional hazard model was used for the risk factors for prognosis of patients with esophageal cancer. Our results indicated reduced levels of volume transfer constant, while increased levels were observed in ADC min , ADC mean , and ADC max following chemoradiotherapy. A negative correlation was determined between ADC min , ADC mean , and ADC max , as well as in the tumor size reduction rate prior to chemoradiotherapy, whereas a positive correlation was uncovered postchemoradiotherapy. Volume transfer constant was positively correlated with tumor size reduction rate both before and after chemoradiotherapy. The 5-year survival rate of patients with esophageal cancer having high ADC min , ADC mean , and ADC max and volume transfer constant before chemoradiotherapy was greater than those with respectively lower values. According to the Cox proportional hazard model, ADC mean , clinical stage, degree of differentiation, and tumor stage were all confirmed as being independent risk factors in regard to the prognosis of patients with EC. The findings of this study provide evidence suggesting that volume transfer constant and apparent diffusion coefficient as being tools allowing for the evaluation of both the short- and long-term efficacies of chemoradiotherapy esophageal cancer treatment.

WE-FG-202-08: Assessment of Treatment Response Via Longitudinal Diffusion MRI On A MRI-Guided System: Initial Experience of Quantitative Analysis

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

Qi, X; Yang, Y; Yang, L

Purpose: To report our initial experience of systematic monitoring treatment response using longitudinal diffusion MR images on a Co-60 MRI-guided radiotherapy system. Methods: Four patients, including 2 head-and-necks, 1 sarcoma and 1 GBM treated on a 0.35 Tesla MRI-guided treatment system, were analyzed. For each patient, 3D TrueFISP MRIs were acquired during CT simulation and before each treatment for treatment planning and patient setup purposes respectively. Additionally, 2D diffusion-weighted MR images (DWI) were acquired weekly throughout the treatment course. The gross target volume (GTV) and brainstem (as a reference structure) were delineated on weekly 3D TrueFISP MRIs to monitor anatomymore » changes, the contours were then transferred onto the corresponding DWI images after fusing with the weekly TrueFISP images. The patient-specific temporal and spatial variations during the entire treatment course, such as anatomic changes, target apparent diffusion coefficient (ADC) distribution were evaluated in a longitudinal pattern. Results: Routine MRI revealed progressive soft-tissue GTV volume changes (up to 53%) for the H&N cases during the treatment course of 5–7 weeks. Within the GTV, the mean ADC values varied from −44% (ADC decrease) to +26% (ADC increase) in a week. The gradual increase of ADC value was inversely associated with target volume variation for one H&N case. The maximal changes of mean ADC values within the brainstem were 5.3% for the H&N cases. For the large size sarcoma and GBM tumors, spatial heterogeneity and temporal variations were observed through longitudinal ADC analysis. Conclusion: In addition to the superior soft-tissue visualization, the 0.35T MR system on ViewRay showed the potential to quantitatively measure the ADC values for both tumor and normal tissues. For normal tissue that is minimally affected by radiation, its ADC values are reproducible. Tumor ADC values show temporal and spatial fluctuation that can be exploited for personalized adaptive therapy.« less

Short Diffusion Time Diffusion-Weighted Imaging With Oscillating Gradient Preparation as an Early Magnetic Resonance Imaging Biomarker for Radiation Therapy Response Monitoring in Glioblastoma: A Preclinical Feasibility Study.

PubMed

Bongers, Andre; Hau, Eric; Shen, Han

2018-01-04

To investigate a novel alternative diffusion-weighted imaging (DWI) approach using oscillating gradients preparation (OGSE) to obtain much shorter effective diffusion times (Δ eff ) for tumor response monitoring by apparent diffusion coefficient (ADC) mapping in a glioblastoma mouse model. Twenty-four BALB/c nude mice inoculated with U87 glioblastoma cells were randomized into a control group and an irradiation group, which underwent a 15-day fractioned radiation therapy (RT) course with 2 Gy/d. Therapy response was assessed by mapping of ADCs at 6 time points using an in-house implementation of a cos-OGSE DWI sequence with Δ eff  = 1.25 ms and compared with a standard pulsed gradient DWI protocol (PGSE) with typical clinical diffusion time Δ eff  = 18 ms. Longitudinal ADC changes in tumor and contralateral white matter (WM) were statistically assessed using repeated-measures analysis of variance and post hoc (Sidak) testing. On short Δ eff OGSE maps tumor ADC was generally 30%-50% higher than in surrounding WM. Areas correlated well with histology. Tumor identification was generally more difficult on PGSE maps owing to nonsignificant WM/tumor contrast. During RT, OGSE maps also showed significant tumor ADC increase (approximately 15%) in response to radiation, consistently seen after 14-Gy RT dose. The clinical reference (PGSE) showed lower sensitivity to radiation changes, and no significant response across the radiation group and time course could be detected. Our short Δ eff DWI method using OGSE better reflected histologically defined tumor areas and enabled more consistent and earlier detection of microstructural radiation changes than conventional methods. Oscillating gradients preparation offers significant potential as a robust microstructural RT response biomarker, potentially helping to shift important therapy decisions to earlier stages in the RT time course. Copyright © 2018 Elsevier Inc. All rights reserved.

Effect of intravascular contrast agent on diffusion and perfusion fraction coefficients in the peripheral zone and prostate cancer.

PubMed

Mazaheri, Yousef; Hötker, Andreas M; Shukla-Dave, Amita; Akin, Oguz; Hricak, Hedvig

2018-09-01

To determine whether water diffusion and the perfusion fraction coefficients in prostate peripheral zone (PZ) and prostate cancer (PCa) are affected by intravenous contrast injection and explore the potential mechanism behind previously reported differences between pre- and post-contrast ADC values. Our institutional review board waived informed consent for this HIPAA-compliant, retrospective study, which included 32 patients (median age, 63 years; range, 47-77 years) with biopsy-proven, untreated PCa who underwent 3-Tesla MRI, including DW-MRI at b-values 0, 400, 700, 1000 s/mm 2 before and after gadolinium injection. For regions of interest (ROIs) in presumed benign PZ and PZ PCa, apparent diffusion coefficient (ADC), perfusion fraction f, and diffusion coefficient D were estimated voxel-wise, and signal-to-noise ratio (SNR) and contrast-to-noise (CNR) were estimated. Pre- and post-contrast measurements were compared by Wilcoxon signed-rank test; P < 0.05 was considered significant. In PZ, f (P = 0.002) was significantly higher on post-contrast imaging than on pre-contrast imaging, but ADC and D values did not change significantly (P = 0.562 and 0.295 respectively). In PCa, all parameters differed significantly between post-contrast and pre-contrast imaging (P < 0.0001 for ADC, P = 0.0084 for D, and P = 0.029 for f). On post-contrast imaging, SNR was not significantly different in PZ (P = 0.260) but was significantly lower in PCa (P < 0.0001); CNR did not change significantly (P = 0.059). After contrast injection, ADC and D declined significantly in PCa only, while f increased significantly in both PCa and PZ. Pre- and post-contrast diffusion parameters cannot be used interchangeably for diagnostic purposes that require quantitative diffusion estimates. Copyright © 2018. Published by Elsevier Inc.

Improving H-Q rating curves in temprorary streams by using Acoustic Doppler Current meters

NASA Astrophysics Data System (ADS)

Marchand, P.; Salles, C.; Rodier, C.; Hernandez, F.; Gayrard, E.; Tournoud, M.-G.

2012-04-01

Intermittent rivers pose different challenges to stream rating due to high spatial and temporal gradients. Long dry periods, cut by short duration flush flood events explain the difficulty to obtain reliable discharge data, for low flows as well as for floods: problems occur with standard gauging, zero flow period, etc. Our study aims to test the use of an acoustic Doppler currentmeter (ADC) for improving stream rating curves in small catchments subject to large variations of discharge, solid transport and high eutrophication levels. The study is conducted at the outlet of the river Vène, a small coastal river (67 km2) located close to the city of Montpellier (France). The low flow period lasts for more than 6 month; during this period the river flow is sustained by effluents from urban sewage systems, which allows development of algae and macrophytes in the riverbed. The ADC device (Sontek ®Argonaut SW) is a pulsed Doppler current profiling system designed for measuring water velocity profiles and levels that are used to compute volumetric flow rates. It is designed for shallow waters (less than 4 meter depth). Its main advantages are its low cost and high accuracy (±1% of the measured velocity or ±0.05 m/sec, as reported by the manufacturer). The study will evaluate the improvement in rating curves in an intermittent flow context and the effect of differences in sensitivity between low and high water level, by comparing mean flow velocity obtained by ADC to direct discharges measurements. The study will also report long-term use of ADC device, by considering effects of biofilms, algae and macrophytes, as well as solid transport on the accuracy of the measurements. In conclusion, we show the possibility to improve stream rating and continuous data collection of an intermittent river by using a ADC with some precautions.

Acute pyelonephritis in transplanted kidneys: can diffusion-weighted magnetic resonance imaging be useful for diagnosis and follow-up?

PubMed

Faletti, Riccardo; Cassinis, Maria Carla; Gatti, Marco; Giglio, Jacopo; Guarnaccia, Carla; Messina, Marina; Bergamasco, Laura; Fonio, Paolo

2016-03-01

To assess reliability of diffusion-weighted magnetic resonance imaging (DW-MRI) in the management of acute pyelonephritis (APN) foci in transplanted kidneys. In the 2012-2014 period, 24 kidney-transplanted patients underwent MR screening for clinical suspicion of APN. Two readers independently analyzed all images, establishing presence and location of APN foci. The 22 patients who were positive at the MR exam constituted the study population. For each patient the apparent diffusion coefficient (ADC) was measured in the APN foci and in three sites of the healthy parenchyma (case-control comparison). The data were matched to the laboratory measurements for white blood cell, C-reactive protein, and serum creatinine. Forty-six APN foci were found in 22/24 patients. At the acute stage, the difference in ADC between healthy parenchyma and APN foci was significant (2.06 ± 0.16 vs. 1.43 ± 0.32 × 10(-3) mm(2)/s; p < 0.0001). The performance of ADC as APN indicator was tested by the receiving operating characteristics (ROC) curve: the area under curve AUC = 0.99 witnessed an excellent discriminatory ability, with threshold APN/normal parenchyma 1.9 × 10(-3) mm(2)/s. At the 1-month follow-up 43/46 APN foci were no longer visible, with ADC values significantly higher than at the acute stage; all laboratory data were physiological, with WBC significantly reduced from the acute phase (5.2 ± 1.6 × 10(9)/L vs. 10.6 ± 4.8 × 10(9)/L; p < 0.0001). The other 3 patients underwent further therapy and exams, including a third MR. DW-MRI with ADC measurement seems to be a reliable tool in diagnosing and monitoring APN foci in transplanted kidneys, with clinical impact on patient management.

Design and characterization of a 12-bit 10MS/s 10mW pipelined SAR ADC for CZT-based hard X-ray imager

NASA Astrophysics Data System (ADS)

Xue, F.; Gao, W.; Duan, Y.; Zheng, R.; Hu, Y.

2018-02-01

This paper presents a 12-bit pipelined successive approximation register (SAR) ADC for CZT-based hard X-ray Imager. The proposed ADC is comprised of a first-stage 6-bit SAR-based Multiplying Digital Analog Converter (MDAC) and a second-stage 8-bit SAR ADC. A novel MDAC architecture using Vcm-based Switching method is employed to maximize the energy efficiency and improve the linearity of the ADC. Moreover, the unit-capacitor array instead of the binary-weighted capacitor array is adopted to improve the conversion speed and linearity of the ADC in the first-stage MDAC. In addition, a new layout design method for the binary-weighted capacitor array is proposed to reduce the capacitor mismatches and make the routing become easier and less-time-consuming. Finally, several radiation-hardened-by-design technologies are adopted in the layout design against space radiation effects. The prototype chip was fabricated in 0.18 μm mixed-signal 1.8V/3.3V process and operated at 1.8 V supply. The chip occupies a core area of only 0.58 mm2. The proposed pipelined SAR ADC achieves a peak signal-to-noise-and-distortion ratio (SNDR) of 66.7 dB and a peak spurious-free dynamic range (SFDR) of 78.6 dB at 10 MS/s sampling rate and consumes 10 mW. The figure of merit (FOM) of the proposed ADC is 0.56 pJ/conversion-step.

Alterations of apparent diffusion coefficient (ADC) in the brain of rats chronically exposed to lead acetate.

PubMed

López-Larrubia, Pilar; Cauli, Omar

2011-03-15

Diffusion-weighted imaging (DWI) allows the assessment of the water apparent diffusion coefficient (ADC), a measure of tissue water diffusivity which is altered during different pathological conditions such as cerebral oedema. By means of DWI, we repeatedly measured in the same rats apparent diffusion coefficient ADC in different brain areas (motor cortex (MCx), somato-sensory cortex (SCx), caudate-putamen (CPu), hippocampus (Hip), mesencephalic reticular formation (RF), corpus callosum (CC) and cerebellum (Cb)) after 1 week, 4 and 12 weeks of lead acetate exposure via drinking water (50 or 500 ppm). After 12 weeks of lead exposure rats received albumin-Evans blue complex administration and were sacrificed 1h later. Blood-brain barrier permeability and water tissue content were determined in order to evaluate their relationship with ADC changes. Chronic exposure to lead acetate (500 ppm) for 4 weeks increased ADC values in Hip, RF and Cb but no in other brain areas. After 12 weeks of lead acetate exposure at 500 ppm ADC is significantly increased also in CPu and CC. Brain areas displaying high ADC values after lead exposure showed also an increased water content and increased BBB permeability to Evans blue-albumin complex. Exposure to 50 ppm for 12 weeks increased ADC values and BBB permeability in the RF and Cb. In summary, chronic lead exposure induces cerebral oedema in the adult brain depending on the brain area and the dose of exposure. RF and Cb appeared the most sensitive brain areas whereas cerebral cortex appears resistant to lead-induced cerebral oedema. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Apparent diffusion coefficient mapping using diffusion-weighted MRI: impact of background parenchymal enhancement, amount of fibroglandular tissue and menopausal status on breast cancer diagnosis.

PubMed

Horvat, Joao V; Durando, Manuela; Milans, Soledad; Patil, Sujata; Massler, Jessica; Gibbons, Girard; Giri, Dilip; Pinker, Katja; Morris, Elizabeth A; Thakur, Sunitha B

2018-06-01

To investigate the impact of background parenchymal enhancement (BPE), amount of fibroglandular tissue (FGT) and menopausal status on apparent diffusion coefficient (ADC) values in differentiation between malignant and benign lesions. In this HIPAA-compliant study, mean ADC values of 218 malignant and 130 benign lesions from 288 patients were retrospectively evaluated. The differences in mean ADC values between benign and malignant lesions were calculated within groups stratified by BPE level (high/low), amount of FGT (dense/non-dense) and menopausal status (premenopausal/postmenopausal). Sensitivities and specificities for distinguishing malignant from benign lesions within different groups were compared for statistical significance. The mean ADC value for malignant lesions was significantly lower compared to that for benign lesions (1.07±0.21 x 10 -3 mm 2 /s vs. 1.53±0.26 x 10 -3 mm 2 /s) (p<0.0001). Using the optimal cut-off point of 1.30 x 10 -3 mm 2 /s, an area under the curve of 0.918 was obtained, with sensitivity and specificity both of 87 %. There was no statistically significant difference in sensitivities and specificities of ADC values between different groups stratified by BPE level, amount of FGT or menopausal status. Differentiation between benign and malignant lesions on ADC values is not significantly affected by BPE level, amount of FGT or menopausal status. • ADC allows differentiation between benign and malignant lesions. • ADC is useful for breast cancer diagnosis despite different patient characteristics. • BPE, FGT or menopause do not significantly affect sensitivity and specificity.

Ghosts, Meaning, and Faith: After-Death Communications in Bereavement Narratives

ERIC Educational Resources Information Center

Kwilecki, Susan

2011-01-01

After-death communications (ADCs) are reported encounters with a deceased loved one, a contemporary type of ghost experience heralded as therapeutic in coping with bereavement. Pertinent literature generally illustrates the healing power of ADCs with brief, self-contained episodes. The functions of ADCs over the course of grief need exploration.…

Site-Specific Antibody–Drug Conjugates: The Nexus of Bioorthogonal Chemistry, Protein Engineering, and Drug Development

PubMed Central

2015-01-01

Antibody–drug conjugates (ADCs) combine the specificity of antibodies with the potency of small molecules to create targeted drugs. Despite the simplicity of this concept, generation of clinically successful ADCs has been very difficult. Over the past several decades, scientists have learned a great deal about the constraints on antibodies, linkers, and drugs as they relate to successful construction of ADCs. Once these components are in hand, most ADCs are prepared by nonspecific modification of antibody lysine or cysteine residues with drug-linker reagents, which results in heterogeneous product mixtures that cannot be further purified. With advances in the fields of bioorthogonal chemistry and protein engineering, there is growing interest in producing ADCs by site-specific conjugation to the antibody, yielding more homogeneous products that have demonstrated benefits over their heterogeneous counterparts in vivo. Here, we chronicle the development of a multitude of site-specific conjugation strategies for assembly of ADCs and provide a comprehensive account of key advances and their roots in the fields of bioorthogonal chemistry and protein engineering. PMID:25494884

Site-specific antibody-drug conjugates: the nexus of bioorthogonal chemistry, protein engineering, and drug development.

PubMed

Agarwal, Paresh; Bertozzi, Carolyn R

2015-02-18

Antibody-drug conjugates (ADCs) combine the specificity of antibodies with the potency of small molecules to create targeted drugs. Despite the simplicity of this concept, generation of clinically successful ADCs has been very difficult. Over the past several decades, scientists have learned a great deal about the constraints on antibodies, linkers, and drugs as they relate to successful construction of ADCs. Once these components are in hand, most ADCs are prepared by nonspecific modification of antibody lysine or cysteine residues with drug-linker reagents, which results in heterogeneous product mixtures that cannot be further purified. With advances in the fields of bioorthogonal chemistry and protein engineering, there is growing interest in producing ADCs by site-specific conjugation to the antibody, yielding more homogeneous products that have demonstrated benefits over their heterogeneous counterparts in vivo. Here, we chronicle the development of a multitude of site-specific conjugation strategies for assembly of ADCs and provide a comprehensive account of key advances and their roots in the fields of bioorthogonal chemistry and protein engineering.

Mathematical modeling of antibody drug conjugates with the target and tubulin dynamics to predict AUC.

PubMed

Byun, Jong Hyuk; Jung, Il Hyo

2018-04-14

Antibody drug conjugates (ADCs)are one of the most recently developed chemotherapeutics to treat some types of tumor cells. They consist of monoclonal antibodies (mAbs), linkers, and potent cytotoxic drugs. Unlike common chemotherapies, ADCs combine selectively with a target at the surface of the tumor cell, and a potent cytotoxic drug (payload) effectively prevents microtubule polymerization. In this work, we construct an ADC model that considers both the target of antibodies and the receptor (tubulin) of the cytotoxic payloads. The model is simulated with brentuximab vedotin, one of ADCs, and used to investigate the pharmacokinetic (PK) characteristics of ADCs in vivo. It also predicts area under the curve (AUC) of ADCs and the payloads by identifying the half-life. The results show that dynamical behaviors fairly coincide with the observed data and half-life and capture AUC. Thus, the model can be used for estimating some parameters, fitting experimental observations, predicting AUC, and exploring various dynamical behaviors of the target and the receptor. Copyright © 2018 Elsevier Ltd. All rights reserved.

Evaluation of Multi-Channel ADCs for Gamma-Ray Spectroscopy

NASA Astrophysics Data System (ADS)

Tan, Hui; Hennig, Wolfgang; Walby, Mark D.; Breus, Dimitry; Harris, Jackson

2013-04-01

As nuclear physicists increasingly design large scale experiments with hundreds or thousands of detector channels, there are growing needs for high density readout electronics with good timing and energy resolution that at the same time offer lower cost per channel compared to existing commercial solutions. Recent improvements in the design of commercial analog to digital converters (ADCs) have resulted in a variety of multi-channel ADCs that are natural choice for designing such high density readout modules. However, multi-channel ADCs typically are designed for medical imaging/ultrasound applications and therefore are not rated for their spectroscopic characteristics. In this work, we evaluated the gamma-ray spectroscopic performance of several multi-channel ADCs, including their energy resolution, nonlinearity, and timing resolution. Some of these ADCs demonstrated excellent energy resolution, 2.66% FWHM at 662 keV with a LaBr3 or 1.78 keV FWHM at 1332.5 keV with a high purity germanium (HPGe) detector, and sub-nanosecond timing resolution with LaBr 3. We present results from these measurements to illustrate their suitability for gamma-ray spectroscopy.

Unresectable Hepatocellular Carcinoma: MR Imaging after Intraarterial Therapy. Part I. Identification and Validation of Volumetric Functional Response Criteria

PubMed Central

Bonekamp, Susanne; Li, Zhen; Geschwind, Jean-François H.; Halappa, Vivek Gowdra; Corona-Villalobos, Celia Pamela; Reyes, Diane; Pawlik, Timothy M.; Bonekamp, David; Eng, John

2013-01-01

Purpose: To identify and validate the optimal thresholds for volumetric functional MR imaging response criteria to predict overall survival after intraarterial treatment (IAT) in patients with unresectable hepatocellular carcinoma (HCC). Materials and Methods: Institutional review board approval and waiver of informed consent were obtained. A total of 143 patients who had undergone MR imaging before and 3–4 weeks after the first cycle of IAT were included. MR imaging analysis of one representative HCC index lesion was performed with proprietary software after initial treatment. Subjects were randomly divided into training (n = 114 [79.7%]) and validation (n = 29 [20.3%]) data sets. Uni- and multivariate Cox models were used to determine the best cutoffs, as well as survival differences, between response groups in the validation data set. Results: Optimal cutoffs in the training data set were 23% increase in apparent diffusion coefficient (ADC) and 65% decrease in volumetric enhancement in the portal venous phase (VE). Subsequently, 25% increase in ADC and 65% decrease in VE were used to stratify patients in the validation data set. Comparison of ADC responders (n = 12 [58.6%]) with nonresponders (n = 17 [34.5%]) showed significant differences in survival (25th percentile survival, 11.2 vs 4.9 months, respectively; P = .008), as did VE responders (n = 9 [31.0%]) compared with nonresponders (n = 20 [69.0%]; 25th percentile survival, 11.5 vs 5.1 months, respectively; P = .01). Stratification of patients with a combination of the criteria resulted in significant differences in survival between patients with lesions that fulfilled both criteria (n = 6 [20.7%]; too few cases to determine 25th percentile), one criterion (n = 9 [31.0%]; 25th percentile survival, 6.0 months), and neither criterion (n = 14 [48.3%]; 25th percentile survival, 5.1 months; P = .01). The association between the two criteria and overall survival remained significant in a multivariate analysis that included age, sex, Barcelona Clinic for Liver Cancer stage, and number of follow-up treatments. Conclusion: After IAT for unresectable HCC, patients can be stratified into significantly different survival categories based on responder versus nonresponder status according to MR imaging ADC and VE cutoffs. © RSNA, 2013 PMID:23616631

SU-F-J-173: Online Replanning for Dose Painting Based On Changing ADC Map of Pancreas Cancer

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

Ates, O; Ahunbay, E; Erickson, B

Purpose: The introduction of MR-guided radiation therapy (RT), e.g., MR-Linac, would allow dose painting to adapt spatial RT response revealed from MRI data during the RT delivery. The purpose of this study is to investigate the use of an online replanning method to adapt dose painting from the MRI Apparent Diffusion Coefficient (ADC) map acquired during the delivery of RT for pancreatic cancers. Methods: Original dose painting plans were created based on multi-parametric simulation MRI including T1, T2 and ADC, using a treatment planning system (MONACO, Elekta) equipped with an online replanning algorithm (WSO, warm start optimization). Multiple GTVs, identifiedmore » based on various ADC levels were prescribed to different doses ranging from 50–70 Gy with simultaneous integrated boost in 28 fractions. The MRI acquired after RT were used to mimic weekly MRI, on which the changing GTVs, pancreatic head and other organs-at-risk (OAR) (duodenum, stomach, small bowel) were delineated. The adaptive plan was generated by applying WSO algorithm starting from the deformed original plan based on the weekly MRI using a deformable image registration (DIR) software (ADMIRE, Elekta). The online replanning method takes <10 min. including DIR, target delineation, WSO execution and final dose calculation. Standard IGRT repositioning and full-blown reoptimization plans were also generated to compare with the adaptive plans. Results: The online replanning method significantly improved the multiple target coverages and OAR sparing for pancreatic cancers. For example, for a case with two GTVs with prescriptions of 60 and 70 Gy in pancreatic head, V100-GTV70 (the volume covered by 100% of prescription dose for GTV with 70 Gy)/V100-GTV60/V100-CTV50/V45-duodenum were (95.1/22.2/69.5/85.7), (95.0/97.0/98.6/34.3), and (95.0/98.1/100.0/38.7) for the IGRT, adaptive and reoptimization plans, respectively. Conclusion: The introduced online adaptive replanning method can effectively account for interfractional changes including tumor spatial response during MR-guided RT delivery, allowing precise delivery of dose painting. This study was partially supported by Elekta Inc.« less

Diffusion-weighted magnetic resonance imaging using different b-value combinations for the evaluation of treatment results after volumetric MR-guided high-intensity focused ultrasound ablation of uterine fibroids.

PubMed

Ikink, Marlijne E; Voogt, Marianne J; van den Bosch, Maurice A A J; Nijenhuis, Robbert J; Keserci, Bilgin; Kim, Young-sun; Vincken, Koen L; Bartels, Lambertus W

2014-09-01

To assess the value of diffusion-weighted magnetic resonance imaging (DWI) and apparent diffusion coefficient (ADC) mapping using different b-value combinations for treatment evaluation after magnetic resonance-guided high-intensity focused ultrasound (MR-HIFU) of uterine fibroids. Fifty-six patients with 67 uterine fibroids were treated with volumetric MR-HIFU. Pre-treatment and post-treatment images were obtained using contrast-enhanced T1-weighted MRI (CE-T1WI) and DWI using b = 0, 200, 400, 600, 800 s/mm(2). ADC maps were generated using subsets of b-values to investigate the effects of tissue ablation on water diffusion and perfusion in fibroids treated with MR-HIFU. Four combinations of b-values were used: (1) all b-values; (2) b = 0, 200 s/mm(2); (3) b = 400, 600, 800 s/mm(2); and (4) b = 0, 800 s/mm(2). Using the lowest b-values (0 and 200 s/mm(2)), the mean ADC value in the ablated tissue reduced significantly (p < 0.001) compared with baseline. Calculating the ADC value with the highest b-values (400, 600, 800 s/mm(2)), the ADC increased significantly (p < 0.001) post-treatment. ADC maps calculated with the lowest b-values resulted in the best visual agreement of non-perfused fibroid tissue detected on CE images. Other b-value combinations and normal myometrium showed no difference in ADC after MR-HIFU treatment. A decrease in contrast agent uptake within the ablated region on CE-T1WI was correlated to a significantly decreased ADC when b = 0 and 200 s/mm(2) were used. DWI could be useful for treatment evaluation after MR-HIFU of uterine fibroids. The ADC in fibroid tissue is influenced by the choice of b- values. Low b-values seem the best choice to emphasise perfusion effects after MR-HIFU.

Comparison of stretched-Exponential and monoexponential model diffusion-Weighted imaging in prostate cancer and normal tissues.

PubMed

Liu, Xiaohang; Zhou, Liangping; Peng, Weijun; Wang, He; Zhang, Yong

2015-10-01

To compare stretched-exponential and monoexponential model diffusion-weighted imaging (DWI) in prostate cancer and normal tissues. Twenty-seven patients with prostate cancer underwent DWI exam using b-values of 0, 500, 1000, and 2000 s/mm(2) . The distributed diffusion coefficients (DDC) and α values of prostate cancer and normal tissues were obtained with stretched-exponential model and apparent diffusion coefficient (ADC) values using monoexponential model. The ADC, DDC (both in 10(-3) mm(2)/s), and α values (range, 0-1) were compared among different prostate tissues. The ADC and DDC were also compared and correlated in each tissue, and the standardized differences between DDC and ADC were compared among different tissues. Data were obtained for 31 cancers, 36 normal peripheral zone (PZ) and 26 normal central gland (CG) tissues. The ADC (0.71 ± 0.12), DDC (0.60 ± 0.18), and α value (0.64 ± 0.05) of tumor were all significantly lower than those of the normal PZ (1.41 ± 0.22, 1.47 ± 0.20, and 0.85 ± 0.09) and CG (1.25 ± 0.14, 1.32 ± 0.13, and 0.82 ± 0.06) (all P < 0.05). ADC was significantly higher than DDC in cancer, but lower than DDC in the PZ and CG (all P < 0.05). The ADC and DDC were strongly correlated (R(2)  = 0.99, 0.98, 0.99, respectively, all P < 0.05) in all the tissue, and standardized difference between ADC and DDC of cancer was slight but significantly higher than that in normal tissue. The stretched-exponential model DWI provides more parameters for distinguishing prostate cancer and normal tissue and reveals slight differences between DDC and ADC values. © 2015 Wiley Periodicals, Inc.

Apparent diffusion coefficient (ADC) does not correlate with different serological parameters in myositis and myopathy.

PubMed

Meyer, Hans-Jonas; Ziemann, Oliver; Kornhuber, Malte; Emmer, Alexander; Quäschling, Ulf; Schob, Stefan; Surov, Alexey

2018-06-01

Background Magnetic resonance imaging (MRI) is widely used in several muscle disorders. Diffusion-weighted imaging (DWI) is an imaging modality, which can reflect microstructural tissue composition. The apparent diffusion coefficient (ADC) is used to quantify the random motion of water molecules in tissue. Purpose To investigate ADC values in patients with myositis and non-inflammatory myopathy and to analyze possible associations between ADC and laboratory parameters in these patients. Material and Methods Overall, 17 patients with several myositis entities, eight patients with non-inflammatory myopathies, and nine patients without muscle disorder as a control group were included in the study (mean age = 55.3 ± 14.3 years). The diagnosis was confirmed by histopathology in every case. DWI was obtained in a 1.5-T scanner using two b-values: 0 and 1000 s/mm 2 . In all patients, the blood sample was acquired within three days to the MRI. The following serological parameters were estimated: C-reactive protein, lactate dehydrogenase, alanine aminotransferase, aspartate aminotransferase, creatine kinase, and myoglobine. Results The estimated mean ADC value for the myositis group was 1.89 ± 0.37 × 10 -3  mm 2 /s and for the non-inflammatory myopathy group was 1.79 ± 0.33 × 10 -3  mm 2 /s, respectively. The mean ADC values (1.15 ± 0.37 × 10 -3  mm 2 /s) were significantly higher to unaffected muscles (vs. myositis P = 0.0002 and vs. myopathy P = 0.0021). There were no significant correlations between serological parameters and ADC values. Conclusion Affected muscles showed statistically significantly higher ADC values than normal muscles. No linear correlations between ADC and serological parameters were identified.

Associations between apparent diffusion coefficient and electromyography parameters in myositis-A preliminary study.

PubMed

Meyer, Hans-Jonas; Emmer, Alexander; Kornhuber, Malte; Surov, Alexey

2018-05-01

MRI is widely used in several muscle disorders. Diffusion-weighted imaging (DWI) is an emergent imaging modality sensitive to microstructural alterations in tissue. The apparent diffusion coefficient (ADC) is used to quantify the random motion of water molecules. Electromyography (EMG) is a clinically used diagnostic tool in myositis. The aim of this study was to elucidate possible associations between ADC values and EMG findings in myositis patients. Seven patients (eight investigated muscles) with myositis (mean age 51.43 ± 19 years) were included in this study. The diagnosis was confirmed by histopathology in every case. DWI was obtained with a 1.5-T scanner using two b-values 0 and 1000 s/mm². In all patients, a needle electromyography (EMG) was performed within 3 days to the MRI. The following EMG parameters were studied: motor unit action potential (MUAP) amplitudes and durations, as well as pathological spontaneous activity. Spearman's correlation coefficient was used to analyze associations between investigated parameters. The estimated mean ADC mean value was 1.51 ± 0.29 × 10 -3  mm²/s, mean ADC min was 1.28 ± 0.27 × 10 -3  mm²/s, and mean ADC max was 1.73 ± 0.28 × 10 -3  mm²/s. Correlation analysis identified significant associations between ADC mean and duration of the MUAP (p   = .78 P = .0279) and between ADC min and duration of the MUAP (p = .85, P = .01). There were no significant differences according to pathological spontaneous activity. ADC mean and ADC min showed strong positive correlations with the duration of the MUAP in myositis patients. Both modalities might similarly reflect muscle fiber loss in myositis patients.

Global analysis of serum microRNAs as potential biomarkers for lung adenocarcinoma.

PubMed

Rani, Sweta; Gately, Kathy; Crown, John; O'Byrne, Ken; O'Driscoll, Lorraine

2013-12-01

Early diagnosis and the ability to predict the most relevant treatment option for individuals is essential to improve clinical outcomes for non-small cell lung cancer (NSCLC) patients. Adenocarcinoma (ADC), a subtype of NSCLC, is the single biggest cancer killer and therefore an urgent need to identify minimally invasive biomarkers to enable early diagnosis. Recent studies, by ourselves and others, indicate that circulating miRNAs have potential as biomarkers. Here we applied global profiling approaches in serum from patients with ADC of the lung to explore if miRNAs have potential as diagnostic biomarkers. This study involved RNA isolation from 80 sera specimens including those from ADC patients (equal numbers of stages 1, 2, 3, and 4) and age- and gender-matched controls (n = 40 each). Six hundred and sixty-seven miRNAs were co-analyzed in these specimens using TaqMan low density arrays and qPCR validation using individual miRNAs. Overall, approximately 390 and 370 miRNAs were detected in ADC and control sera, respectively. A group of 6 miRNAs, miR-30c-1* (AUC = 0.74; P<0.002), miR-616* (AUC = 0.71; P = 0.001), miR-146b-3p (AUC = 0.82; P<0.0001), miR-566 (AUC = 0.80; P<0.0001), miR-550 (AUC = 0.72; P = 0.0006), and miR-939 (AUC = 0.82; P<0.0001) was found to be present at substantially higher levels in ADC compared with control sera. Conversely, miR-339-5p and miR-656 were detected at substantially lower levels in ADC sera (co-analysis resulting in AUC = 0.6; P = 0.02). Differences in miRNA profile identified support circulating miRNAs having potential as diagnostic biomarkers for ADC. More extensive studies of ADC and control serum specimens are warranted to independently validate the potential clinical relevance of these miRNAs as minimally invasive biomarkers for ADC.

Apparent diffusion coefficients in prostate cancer: correlation with molecular markers Ki-67, HIF-1α and VEGF.

PubMed

Ma, Teng; Yang, Shaolin; Jing, Haiyan; Cong, Lin; Cao, Zhixin; Liu, Zhiling; Huang, Zhaoqin

2018-03-01

Prostate cancer (PCa) is the second most common cancer in men. The Gleason score (GS) and biomarkers play important roles in the diagnosis and treatment of patients with PCa. The purpose of this study was to investigate the relationship between the apparent diffusion coefficient (ADC) and the molecular markers Ki-67, hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) in PCa. Thirty-nine patients with 39 lesions, who had been diagnosed with PCa, were enrolled in this study. All patients underwent diffusion-weighted magnetic resonance imaging (DW-MRI) (b = 800 s/mm 2 ). The expression of Ki-67, HIF-1α and VEGF was assessed by immunohistochemistry. Statistical analysis was applied to analyze the association between ADC and prostate-specific antigen (PSA), GS and the expression of Ki-67, HIF-1α and VEGF. The group differences in ADC among different grades of Ki-67, HIF-1α and VEGF were also analyzed. The mean ± standard deviation of ADC was (0.76 ± 0.27) × 10 -3  mm 2 /s. ADC correlated negatively with PSA and GS (p < 0.05). The Ki-67 staining index (SI), HIF-1α expression and VEGF expression in PCa were correlated inversely with ADC, controlling for age (r = -0.332, p < 0.05; r = -0.662, p < 0.0005; and r = -0.714, p < 0.0005, respectively). ADC showed a significant difference among different grades of Ki-67 (F = 9.164, p = 0.005), HIF-1α (F = 40.333, p < 0.0005) and VEGF (F = 22.048, p < 0.0005). In conclusion, ADC was correlated with PSA, GS, and Ki-67, HIF-1α and VEGF expression in patients with PCa. ADC may be used to evaluate tumor proliferation, hypoxia and angiogenesis in PCa. Copyright © 2018 John Wiley & Sons, Ltd.

A Longitudinal Magnetic Resonance Imaging Study of the Apparent Diffusion Coefficient Values in Corpus Callosum during the First Year after Traumatic Brain Injury

PubMed Central

Håberg, Asta Kristine; Skandsen, Toril; Finnanger, Torun Gangaune; Vik, Anne

2014-01-01

Abstract The objective of this study was to explore the evolution of apparent diffusion coefficient (ADC) values in magnetic resonance imaging (MRI) in normal-appearing tissue of the corpus callosum during the 1st year after traumatic brain injury (TBI), and relate findings to outcome. Fifty-seven patients (mean age 34 [range 11–63] years) with moderate to severe TBI were examined with diffusion weighted MRI at three time points (median 7 days, 3 and 12 months), and a sex- and age-matched control group of 47 healthy individuals, were examined once. The corpus callosum was subdivided and the mean ADC values computed blinded in 10 regions of interests without any visible lesions in the ADC map. Outcome measures were Glasgow Outcome Scale Extended (GOSE) and neuropsychological domain scores at 12 months. We found a gradual increase of the mean ADC values during the 12 month follow-up, most evident in the posterior truncus (r=0.19, p<0.001). Compared with the healthy control group, we found higher mean ADC values in posterior truncus both at 3 months (p=0.021) and 12 months (p=0.003) post-injury. Patients with fluid-attenuated inversion recovery (FLAIR) lesions in the corpus callosum in the early MRI, and patients with disability (GOSE score ≤6) showed evidence of increased mean ADC values in the genu and posterior truncus at 12 months. Mean ADC values in posterior parts of the corpus callosum at 3 months predicted the sensory-motor function domain score (p=0.010–0.028). During the 1st year after moderate and severe TBI, we demonstrated a slowly evolving disruption of the microstructure in normal appearing corpus callosum in the ADC map, most evident in the posterior truncus. The mean ADC values were associated with both outcome and ability to perform speeded, complex sensory-motor action. PMID:23837731

Differences in Brain Morphological Findings between Narcolepsy with and without Cataplexy

PubMed Central

Nakamura, Masaki; Nishida, Shingo; Hayashida, Kenichi; Ueki, Yoichiro; Dauvilliers, Yves; Inoue, Yuichi

2013-01-01

Objective Maps of fractional anisotropy (FA) and apparent diffusion coefficient (ADC) obtained by diffusion tensor imaging (DTI) can detect microscopic axonal changes by estimating the diffusivity of water molecules using magnetic resonance imaging (MRI). We applied an MRI voxel-based statistical approach to FA and ADC maps to evaluate microstructural abnormalities in the brain in narcolepsy and to investigate differences between patients having narcolepsy with and without cataplexy. Methods Twelve patients with drug-naive narcolepsy with cataplexy (NA/CA), 12 with drug-naive narcolepsy without cataplexy (NA w/o CA) and 12 age-matched healthy normal controls (NC) were enrolled. FA and ADC maps for these 3 groups were statistically compared by using voxel-based one-way ANOVA. In addition, we investigated the correlation between FA and ADC values and clinical variables in the patient groups. Results Compared to the NC group, the NA/CA group showed higher ADC values in the left inferior frontal gyrus and left amygdala, and a lower ADC value in the left postcentral gyrus. The ADC value in the right inferior frontal gyrus and FA value in the right precuneus were higher for NA/CA group than for the NA w/o CA group. However, no significant differences were observed in FA and ADC values between the NA w/o CA and NC groups in any of the areas investigated. In addition, no correlation was found between the clinical variables and ADC and FA values of any brain areas in these patient groups. Conclusions Several microstructural changes were noted in the inferior frontal gyrus and amygdala in the NA/CA but not in the NA w/o CA group. These findings suggest that these 2 narcolepsy conditions have different pathological mechanisms: narcolepsy without cataplexy form appears to be a potentially broader condition without any significant brain imaging differences from normal controls. PMID:24312261

Liver diffusion-weighted MR imaging: reproducibility comparison of ADC measurements obtained with multiple breath-hold, free-breathing, respiratory-triggered, and navigator-triggered techniques.

PubMed

Chen, Xin; Qin, Lei; Pan, Dan; Huang, Yanqi; Yan, Lifen; Wang, Guangyi; Liu, Yubao; Liang, Changhong; Liu, Zaiyi

2014-04-01

To prospectively compare the reproducibility of normal liver apparent diffusion coefficient (ADC) measurements by using different respiratory motion compensation techniques with multiple breath-hold (MBH), free-breathing (FB), respiratory-triggered (RT), and navigator-triggered (NT) diffusion-weighted (DW) imaging and to compare the ADCs at different liver anatomic locations. The study protocol was approved by the institutional review board, and written informed consent was obtained from each participant. Thirty-nine volunteers underwent liver DW imaging twice. Imaging was performed with a 1.5-T MR imager with MBH, FB, RT, and NT techniques (b = 0, 100, and 500 sec/mm(2)). Three representative sections--superior, central, and inferior--were selected on left and right liver lobes, respectively. On each selected section, three regions of interest were drawn, and ADCs were measured. Analysis of variance was used to assess ADCs among the four techniques and various anatomic locations. Reproducibility of ADCs was assessed with the Bland-Altman method. ADCs obtained with MBH (range: right lobe, [1.641-1.662] × 10(-3)mm(2)/sec; left lobe, [2.034-2.054] ×10(-3)mm(2)/sec) were higher than those obtained with FB (right, [1.349-1.391] ×10(-3)mm(2)/sec; left, [1.630-1.700] ×10(-3)mm(2)/sec), RT (right, [1.439-1.455] ×10(-3)mm(2)/sec; left, [1.720-1.755] ×10(-3)mm(2)/sec), or NT (right, [1.387-1.400] ×10(-3)mm(2)/sec; left, [1.661-1.736] ×10(-3)mm(2)/sec) techniques (P < .001); however, no significant difference was observed between ADCs obtained with FB, RT, and NT techniques (P = .130 to P >.99). ADCs showed a trend to decrease moving from left to right. Reproducibility in the left liver lobe was inferior to that in the right, and the central middle segment in the right lobe had the most reproducible ADC. Statistical differences in ADCs were observed in the left-right direction in the right lobe (P < .001), but they were not observed in the superior-inferior direction (P = .144-.450). However, in the left liver lobe, statistical differences existed in both directions (P = .001 to P = .016 in the left-right direction, P < .001 in the superior-inferior direction). Both anatomic location and DW imaging technique influence liver ADC measurements and their reproducibility. FB DW imaging is recommended for liver DW imaging because of its good reproducibility and shorter acquisition time compared with that of MBH, RT, and NT techniques. RSNA, 2014

Analysis and correction of gradient nonlinearity bias in apparent diffusion coefficient measurements.

PubMed

Malyarenko, Dariya I; Ross, Brian D; Chenevert, Thomas L

2014-03-01

Gradient nonlinearity of MRI systems leads to spatially dependent b-values and consequently high non-uniformity errors (10-20%) in apparent diffusion coefficient (ADC) measurements over clinically relevant field-of-views. This work seeks practical correction procedure that effectively reduces observed ADC bias for media of arbitrary anisotropy in the fewest measurements. All-inclusive bias analysis considers spatial and time-domain cross-terms for diffusion and imaging gradients. The proposed correction is based on rotation of the gradient nonlinearity tensor into the diffusion gradient frame where spatial bias of b-matrix can be approximated by its Euclidean norm. Correction efficiency of the proposed procedure is numerically evaluated for a range of model diffusion tensor anisotropies and orientations. Spatial dependence of nonlinearity correction terms accounts for the bulk (75-95%) of ADC bias for FA = 0.3-0.9. Residual ADC non-uniformity errors are amplified for anisotropic diffusion. This approximation obviates need for full diffusion tensor measurement and diagonalization to derive a corrected ADC. Practical scenarios are outlined for implementation of the correction on clinical MRI systems. The proposed simplified correction algorithm appears sufficient to control ADC non-uniformity errors in clinical studies using three orthogonal diffusion measurements. The most efficient reduction of ADC bias for anisotropic medium is achieved with non-lab-based diffusion gradients. Copyright © 2013 Wiley Periodicals, Inc.

Diffusion-weighted magnetic resonance imaging in the characterization of testicular germ cell neoplasms: Effect of ROI methods on apparent diffusion coefficient values and interobserver variability.

PubMed

Tsili, Athina C; Ntorkou, Alexandra; Astrakas, Loukas; Xydis, Vasilis; Tsampalas, Stavros; Sofikitis, Nikolaos; Argyropoulou, Maria I

2017-04-01

To evaluate the difference in apparent diffusion coefficient (ADC) measurements at diffusion-weighted (DW) magnetic resonance imaging of differently shaped regions-of-interest (ROIs) in testicular germ cell neoplasms (TGCNS), the diagnostic ability of differently shaped ROIs in differentiating seminomas from nonseminomatous germ cell neoplasms (NSGCNs) and the interobserver variability. Thirty-three TGCNs were retrospectively evaluated. Patients underwent MR examinations, including DWI on a 1.5-T MR system. Two observers measured mean tumor ADCs using four distinct ROI methods: round, square, freehand and multiple small, round ROIs. The interclass correlation coefficient was analyzed to assess interobserver variability. Statistical analysis was used to compare mean ADC measurements among observers, methods and histologic types. All ROI methods showed excellent interobserver agreement, with excellent correlation (P<0.001). Multiple, small ROIs provided the lower mean ADC in TGCNs. Seminomas had lower mean ADC compared to NSGCNs for each ROI method (P<0.001). Round ROI proved the most accurate method in characterizing TGCNS. Interobserver variability in ADC measurement is excellent, irrespective of the ROI shape. Multiple, small round ROIs and round ROI proved the more accurate methods for ADC measurement in the characterization of TGCNs and in the differentiation between seminomas and NSGCNs, respectively. Copyright © 2017 Elsevier B.V. All rights reserved.

Application of 23Na MRI to Monitor Chemotherapeutic Response in RIF-1 Tumors1

PubMed Central

Babsky, Andriy M; Hekmatyar, Shahryar K; Zhang, Hong; Solomon, James L; Bansal, Navin

2005-01-01

Abstract Effects of an alkylating anticancer drug, cyclophosphamide (Cp), on 23Na signal intensity (23Na SI) and water apparent diffusion coefficient (ADC) were examined in subcutaneously-implanted radiation-induced fibrosarcoma (RIF-1) tumors by in vivo 23Na and 1H magnetic resonance imaging (MRI). MRI experiments were performed on untreated control (n = 5) and Cp-treated (n = 6) C3H mice, once before Cp injection (300 mg/kg) then daily for 3 days after treatment. Tumor volumes were significantly lower in treated animals 2 and 3 days posttreatment. At the same time points, MRI experiments showed an increase in both 23Na SI and water ADC in treated tumors, whereas control tumors did not show any significant changes. The correlation between 23Na SI and water ADC changes was dramatically increased in the Cp-treated group, suggesting that the observed increases in 23Na SI and water ADC were caused by the same mechanism. Histologic sections showed decreased cell density in the regions of increased 23Na and water ADC SI. Destructive chemical analysis showed that Cp treatment increased the relative extracellular space and tumor [Na+]. We conclude that the changes in water ADC and 23Na SI were largely due to an increase in extracellular space. 23Na MRI and 1H water ADC measurements may provide valuable noninvasive techniques for monitoring chemotherapeutic responses. PMID:16026645

Resolution-Adaptive Hybrid MIMO Architectures for Millimeter Wave Communications

NASA Astrophysics Data System (ADS)

Choi, Jinseok; Evans, Brian L.; Gatherer, Alan

2017-12-01

In this paper, we propose a hybrid analog-digital beamforming architecture with resolution-adaptive ADCs for millimeter wave (mmWave) receivers with large antenna arrays. We adopt array response vectors for the analog combiners and derive ADC bit-allocation (BA) solutions in closed form. The BA solutions reveal that the optimal number of ADC bits is logarithmically proportional to the RF chain's signal-to-noise ratio raised to the 1/3 power. Using the solutions, two proposed BA algorithms minimize the mean square quantization error of received analog signals under a total ADC power constraint. Contributions of this paper include 1) ADC bit-allocation algorithms to improve communication performance of a hybrid MIMO receiver, 2) approximation of the capacity with the BA algorithm as a function of channels, and 3) a worst-case analysis of the ergodic rate of the proposed MIMO receiver that quantifies system tradeoffs and serves as the lower bound. Simulation results demonstrate that the BA algorithms outperform a fixed-ADC approach in both spectral and energy efficiency, and validate the capacity and ergodic rate formula. For a power constraint equivalent to that of fixed 4-bit ADCs, the revised BA algorithm makes the quantization error negligible while achieving 22% better energy efficiency. Having negligible quantization error allows existing state-of-the-art digital beamformers to be readily applied to the proposed system.

Molecular characterization of dihydroneopterin aldolase and aminodeoxychorismate synthase in common bean-genes coding for enzymes in the folate synthesis pathway.

PubMed

Xie, Weilong; Perry, Gregory; Martin, C Joe; Shim, Youn-Seb; Navabi, Alireza; Pauls, K Peter

2017-07-01

Common beans (Phaseolus vulgaris) are excellent sources of dietary folates, but different varieties contain different amounts of these compounds. Genes coding for dihydroneopterin aldolase (DHNA) and aminodeoxychorismate synthase (ADCS) of the folate synthesis pathway were characterized by PCR amplification, BAC clone sequencing, and whole genome sequencing. All DHNA and ADCS genes in the Mesoamerican cultivar OAC Rex were isolated and compared with those genes in the genome of Andean genotype G19833. Both genotypes have two functional DHNA genes and one pseudo gene. PvDHNA1 and PvDHNA2 proteins have similar secondary structures and conserved residues as DHNA homologs in Staphylococcus aureus and Arabidopsis. Sequence analysis and synteny mapping indicated that PvDHNA1 might be a duplicated and transposed copy of PvDHNA2. There is only one ADCS gene (PvADCS) identified in the bean genome and it is identical in OAC Rex and G19833. PvADCS has the conserved motifs required for catalytic activity similar to other plant ADCS homologs. DHNA and ADCS gene-specific markers were developed, mapped, and compared to their physical locations on chromosomes 1 and 7, respectively. The gene-specific markers developed in this study should be useful for detection and selection of varieties with enhanced folate contents in bean breeding programs.

[Effect of exercise load on apparent diffusion coefficient and fractional anisotropy of normal lumbar intervertebral discs in diffusion tensor imaging].

PubMed

Zhong, Xiu; Qiu, Shijun

2015-06-01

To investigate the effect of exercise load on apparent diffusion coefficient (ADC) and fractional anisotropy (FA) of normal lumbar intervertebral discs in magnetic resonance (MR) diffusion tensor imaging (DTI). Thirty healthy volunteers (24 males and 6 females, aged 19 to 25 years) underwent examinations with MR T2WI and DTI of the lumbar intervertebral discs before and after exercise load. Pfirrmann grading was evaluated with T2WI, and the B0 map, ADC map and FA map were reconstructed based on the DTI data to investigate the changes in ADC and FA after exercise. Of the 30 volunteers (150 intervertebral discs) receiving the examination, 27 with discs of Pfirrminn grade II were included for analysis. In these 27 volunteers, the average ADC and FA before exercise were (1.99 ± 0.18)×10⁻³ mm²/s and 0.155∓0.059, respectively. After exercise, ADC was lowered significantly to (1.93 ± 0.17)×10⁻³ mm²/s (P<0.05) and FA increased slightly to 0.1623 ± 0.017 (P>0.05). DTI allows quantitatively analysis of the changes in water molecular diffusion and anisotropy of the lumbar intervertebral discs after exercise load, which can cause a decreased ADC and a increased FA value, and the change of ADC is more sensitive to exercise load.

Investigating Barriers in HIV-Testing Oncology Patients: The IBITOP Study, Phase I.

PubMed

Merz, Laurent; Zimmermann, Stefan; Peters, Solange; Cavassini, Matthias; Darling, Katharine E A

2016-10-01

Although the prevalence of non-AIDS-defining cancers (non-ADCs) among people living with HIV is rising, we observed HIV testing rates below 5% at our oncology center, against a regional HIV prevalence of 0.2%-0.4%. We performed the Investigating Barriers in HIV-Testing Oncology Patients (IBITOP) study among oncology physicians and patients. Between July 1 and October 31, 2013, patients of unknown HIV status newly diagnosed with solid-organ non-ADCs referred to Lausanne University Hospital Oncology Service, Switzerland, were offered free HIV testing as part of their oncology work-up. The primary endpoints were (a) physician willingness to offer and patient acceptance of HIV testing and (b) physicians' reasons for not offering testing. Of 239 patients of unknown HIV status with a new non-ADC diagnosis, 43 (18%) were offered HIV testing, of whom 4 declined (acceptance rate: 39 of 43; 91%). Except for 21 patients tested prior to oncology consultation, 175 patients (of 239; 73%) were not offered testing. Testing rate declined among patients who were >70 years old (12% versus 30%; p = .04); no non-European patients were tested. Physicians gave reasons for not testing in 16% of cases, the main reason being patient follow-up elsewhere (10 patients; 5.7%). HIV testing during the IBITOP study increased the HIV testing rate to 18%. Although the IBITOP study increased HIV testing rates, most patients were not tested. Testing was low or nonexistent among individuals at risk of late HIV presentation (older patients and migrants). Barriers to testing appear to be physician-led, because patient acceptance of testing offered was very high (91%). In November 2013, the Swiss HIV testing recommendations were updated to propose testing in cancer patients. Phase II of the IBITOP study is examining the effect of these recommendations on HIV testing rates and focusing on physician-led testing barriers. Patients of unknown HIV status newly diagnosed with solid-organ non-AIDS-defining cancers were offered free HIV testing. Physician and patient barriers to HIV testing were examined. Most patients (82%) were not offered testing, and testing of individuals at risk of late HIV presentation (older patients and migrants) was low or nonexistent. Conversely, patient acceptance of testing offered was very high (91%), suggesting that testing barriers in this setting are physician-led. Since this study, the Swiss HIV testing recommendations now advise testing cancer patients before chemotherapy. Phase II of the Investigating Barriers in HIV-Testing Oncology Patients study is examining the effect of these recommendations on testing rates and physician barriers. ©AlphaMed Press.

SU-E-J-136: Multimodality-Image-Based Target Delineation for Dose Painting of Pancreatic Cancer

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

Dalah, E; Paulson, E; Erickson, B

Purpose: Dose escalated RT may provide improved disease local-control for selected unresectable pancreatic cancer. Accurate delineation of the gross tumor volume (GTV) inside pancreatic head or body would allow safe dose escalation considering the tolerances of adjacent organs at risk (OAR). Here we explore the potential of multi-modality imaging (DCE-MRI, ADC-MRI, and FDG-PET) to define the GTV for dose painting of pancreatic cancer. Volumetric variations of DCE-MRI, ADC-MRI and FDG-PET defined GTVs were assessed in comparison to the findings on CT, and to pathology specimens for resectable and borderline reseactable cases of pancreatic cancer. Methods: A total of 19 representativemore » patients with DCE-MRI, ADC-MRI and FDG-PET data were analyzed. Of these, 8 patients had pathological specimens. GTV, inside pancreatic head/neck, or body, were delineated on MRI (denoted GTVDCE, and GTVADC), on FDG-PET using SUV of 2.5, 40% SUVmax, and 50% SUVmax (denoted GTV2.5, GTV40%, and GTV50%). A Kruskal-Wallis test was used to determine whether significant differences existed between GTV volumes. Results: Significant statistical differences were found between the GTVs defined by DCE-MRI, ADC-MRI, and FDG-PET, with a mean and range of 4.73 (1.00–9.79), 14.52 (3.21–25.49), 22.04 (1.00–45.69), 19.10 (4.84–45.59), and 9.80 (0.32–35.21) cm3 (p<0.0001) for GTVDCE, GTVADC, GTV2.5, GTV40%, and GTV50%, respectively. The mean difference and range in the measurements of maximum dimension of GTVs based on DCE-MRI, ADC-MRI, SUV2.5, 40% SUVmax, and 50% SUVmax compared with pathologic specimens were −0.84 (−2.24 to 0.9), 0.41 (−0.15 to 2.3), 0.58 (−1.41 to 3.69), 0.66 (−0.67 to 1.32), and 0.15 (−1.53 to 2.38) cm, respectively. Conclusion: Differences exists between DCE, ADC, and PET defined target volumes for RT of pancreatic cancer. Further studies combined with pathological specimens are required to identify the optimal imaging modality and/or acquisition method to define the GTV.« less

Predicting liver metastasis of gastrointestinal tract cancer by diffusion-weighted imaging of apparent diffusion coefficient values

PubMed Central

Zheng, De-Xian; Meng, Shu-Chun; Liu, Qing-Jun; Li, Chuan-Ting; Shang, Xi-Dan; Zhu, Yu-Seng; Bai, Tian-Jun; Xu, Shi-Ming

2016-01-01

AIM: To determine if efficacy of chemotherapy on liver metastasis of gastrointestinal tract cancer can be predicted by apparent diffusion coefficient (ADC) values of diffusion-weighted imaging (DWI). METHODS: In total, 86 patients with liver metastasis of gastrointestinal tract cancer (156 metastatic lesions) diagnosed in our hospital were included in this study. The maximum diameters of these tumors were compared with each other before treatment, 2 wk after treatment, and 12 wk after treatment. Selected patients were classified as the effective group and the ineffective group, depending on the maximum diameter of the tumor after 12 wk of treatment; and the ADC values at different treatment times between the two groups were compared. Spearman rank correlation was used to analyze the relationship between ADC value and tumor diameter. Receiver operating characteristic curve (ROC curve) was used to analyze the ADC values before treatment to predict the patient’s sensitivity and specificity degree of efficacy to the chemotherapy. RESULTS: There was no difference in age between the two groups and in maximum tumor diameter before treatment and 2 wk after treatment. However, after 12 wk of treatment, maximum tumor diameter in the effective group was significantly lower than that in the ineffective group (P < 0.05). Before treatment, ADC values in the ineffective group were significantly higher than those in the effective group (P < 0.05). There was no difference in ADC values between the effective and ineffective groups after 2 and 12 wk of treatment. However, ADC values were significantly higher after 2 and 12 wk of treatment compared to before treatment in the effective group (P < 0.05). Spearman rank correlation analysis showed that ADC value before treatment and the reduced percentage of the maximum tumor diameter after 12 wk of treatment were negatively correlated, while the increase in the percentage of the ADC value 12 wk after treatment and the decrease in the percentage of the maximum tumor diameter were significantly positively correlated. The results of the ROC curve showed that ADC value with a chemotherapy ineffective threshold value of 1.14 × 10-3 mm2/s before treatment had a sensitivity and specificity of 94.3% and 76.7%, respectively. CONCLUSION: DWI ADC values can be used to predict the response of patients with liver metastasis of gastrointestinal tract cancer to chemotherapy with high sensitivity and relatively high specificity. PMID:26973399

A comparison of automated dispensing cabinet optimization methods.

PubMed

O'Neil, Daniel P; Miller, Adam; Cronin, Daniel; Hatfield, Chad J

2016-07-01

Results of a study comparing two methods of optimizing automated dispensing cabinets (ADCs) are reported. Eight nonprofiled ADCs were optimized over six months. Optimization of each cabinet involved three steps: (1) removal of medications that had not been dispensed for at least 180 days, (2) movement of ADC stock to better suit end-user needs and available space, and (3) adjustment of par levels (desired on-hand inventory levels). The par levels of four ADCs (the Day Supply group) were adjusted according to average daily usage; the par levels of the other four ADCs (the Formula group) were adjusted using a standard inventory formula. The primary outcome was the vend:fill ratio, while secondary outcomes included total inventory, inventory cost, quantity of expired medications, and ADC stockout percentage. The total number of medications stocked in the eight machines was reduced from 1,273 in a designated two-month preoptimization period to 1,182 in a designated two-month postoptimization period, yielding a carrying cost savings of $44,981. The mean vend:fill ratios before and after optimization were 4.43 and 4.46, respectively. The vend:fill ratio for ADCs in the Formula group increased from 4.33 before optimization to 5.2 after optimization; in the Day Supply group, the ratio declined (from 4.52 to 3.90). The postoptimization interaction difference between the Formula and Day Supply groups was found to be significant (p = 0.0477). ADC optimization via a standard inventory formula had a positive impact on inventory costs, refills, vend:fill ratios, and stockout percentages. Copyright © 2016 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

Diffusion tensor imaging of white matter after cranial radiation in children for medulloblastoma: correlation with IQ.

PubMed

Mabbott, Donald J; Noseworthy, Michael D; Bouffet, Eric; Rockel, Conrad; Laughlin, Suzanne

2006-07-01

Treatment of children with cranial-spinal radiation (CSR) for brain tumors is associated with adverse intellectual outcome and white matter damage. However, the correlation between IQ and measures of white matter integrity has received little attention. We examined apparent diffusion coefficient (ADC), fractional anisotropy (FA), and intelligence in pediatric patients treated with CSR for medulloblastoma relative to control subjects. ADC and FA measures were obtained for eight patients and eight control children and evaluated in multiple regions of interest in the cerebral hemispheres. Mean ADC and mean FA for each region were calculated, group differences were evaluated, and the relationship between these measures and intelligence were examined. In our study group, decreased IQ was associated with increased ADC and decreased FA (P < 0.01). Mean IQ for the CSR group was lower than that for the control group, but the difference was not significant when controlling for overall mean FA or ADC (P > 0.10). Overall mean FA was lower and ADC was higher in the CSR group relative to controls (P < 0.01). Specifically, FA was lower in the genu of the corpus callosum, the anterior and posterior limbs of the internal capsule, inferior frontal white matter, and high frontal white matter, and ADC was higher in all regions in patients relative to controls (P < 0.01). Compromised white matter integrity was observed for multiple regions within the cerebral hemispheres following CSR. A novel finding was that microscopic damage in normal-appearing white matter, as indexed by higher ADC and lower FA, was related to poor intellectual outcome relative to age-matched controls.

Measuring the apparent diffusion coefficient in primary rectal tumors: is there a benefit in performing histogram analyses?

PubMed

van Heeswijk, Miriam M; Lambregts, Doenja M J; Maas, Monique; Lahaye, Max J; Ayas, Z; Slenter, Jos M G M; Beets, Geerard L; Bakers, Frans C H; Beets-Tan, Regina G H

2017-06-01

The apparent diffusion coefficient (ADC) is a potential prognostic imaging marker in rectal cancer. Typically, mean ADC values are used, derived from precise manual whole-volume tumor delineations by experts. The aim was first to explore whether non-precise circular delineation combined with histogram analysis can be a less cumbersome alternative to acquire similar ADC measurements and second to explore whether histogram analyses provide additional prognostic information. Thirty-seven patients who underwent a primary staging MRI including diffusion-weighted imaging (DWI; b0, 25, 50, 100, 500, 1000; 1.5 T) were included. Volumes-of-interest (VOIs) were drawn on b1000-DWI: (a) precise delineation, manually tracing tumor boundaries (2 expert readers), and (b) non-precise delineation, drawing circular VOIs with a wide margin around the tumor (2 non-experts). Mean ADC and histogram metrics (mean, min, max, median, SD, skewness, kurtosis, 5th-95th percentiles) were derived from the VOIs and delineation time was recorded. Measurements were compared between the two methods and correlated with prognostic outcome parameters. Median delineation time reduced from 47-165 s (precise) to 21-43 s (non-precise). The 45th percentile of the non-precise delineation showed the best correlation with the mean ADC from the precise delineation as the reference standard (ICC 0.71-0.75). None of the mean ADC or histogram parameters showed significant prognostic value; only the total tumor volume (VOI) was significantly larger in patients with positive clinical N stage and mesorectal fascia involvement. When performing non-precise tumor delineation, histogram analysis (in specific 45th ADC percentile) may be used as an alternative to obtain similar ADC values as with precise whole tumor delineation. Histogram analyses are not beneficial to obtain additional prognostic information.

The histogram analysis of diffusion-weighted intravoxel incoherent motion (IVIM) imaging for differentiating the gleason grade of prostate cancer.

PubMed

Zhang, Yu-Dong; Wang, Qing; Wu, Chen-Jiang; Wang, Xiao-Ning; Zhang, Jing; Liu, Hui; Liu, Xi-Sheng; Shi, Hai-Bin

2015-04-01

To evaluate histogram analysis of intravoxel incoherent motion (IVIM) for discriminating the Gleason grade of prostate cancer (PCa). A total of 48 patients pathologically confirmed as having clinically significant PCa (size > 0.5 cm) underwent preoperative DW-MRI (b of 0-900 s/mm(2)). Data was post-processed by monoexponential and IVIM model for quantitation of apparent diffusion coefficients (ADCs), perfusion fraction f, diffusivity D and pseudo-diffusivity D*. Histogram analysis was performed by outlining entire-tumour regions of interest (ROIs) from histological-radiological correlation. The ability of imaging indices to differentiate low-grade (LG, Gleason score (GS) ≤6) from intermediate/high-grade (HG, GS > 6) PCa was analysed by ROC regression. Eleven patients had LG tumours (18 foci) and 37 patients had HG tumours (42 foci) on pathology examination. HG tumours had significantly lower ADCs and D in terms of mean, median, 10th and 75th percentiles, combined with higher histogram kurtosis and skewness for ADCs, D and f, than LG PCa (p < 0.05). Histogram D showed relatively higher correlations (ñ = 0.641-0.668 vs. ADCs: 0.544-0.574) with ordinal GS of PCa; and its mean, median and 10th percentile performed better than ADCs did in distinguishing LG from HG PCa. It is feasible to stratify the pathological grade of PCa by IVIM with histogram metrics. D performed better in distinguishing LG from HG tumour than conventional ADCs. • GS had relatively higher correlation with tumour D than ADCs. • Difference of histogram D among two-grade tumours was statistically significant. • D yielded better individual features in demonstrating tumour grade than ADC. • D* and f failed to determine tumour grade of PCa.

Non-small cell lung cancer: Whole-lesion histogram analysis of the apparent diffusion coefficient for assessment of tumor grade, lymphovascular invasion and pleural invasion.

PubMed

Tsuchiya, Naoko; Doai, Mariko; Usuda, Katsuo; Uramoto, Hidetaka; Tonami, Hisao

2017-01-01

Investigating the diagnostic accuracy of histogram analyses of apparent diffusion coefficient (ADC) values for determining non-small cell lung cancer (NSCLC) tumor grades, lymphovascular invasion, and pleural invasion. We studied 60 surgically diagnosed NSCLC patients. Diffusion-weighted imaging (DWI) was performed in the axial plane using a navigator-triggered single-shot, echo-planar imaging sequence with prospective acquisition correction. The ADC maps were generated, and we placed a volume-of-interest on the tumor to construct the whole-lesion histogram. Using the histogram, we calculated the mean, 5th, 10th, 25th, 50th, 75th, 90th, and 95th percentiles of ADC, skewness, and kurtosis. Histogram parameters were correlated with tumor grade, lymphovascular invasion, and pleural invasion. We performed a receiver operating characteristics (ROC) analysis to assess the diagnostic performance of histogram parameters for distinguishing different pathologic features. The ADC mean, 10th, 25th, 50th, 75th, 90th, and 95th percentiles showed significant differences among the tumor grades. The ADC mean, 25th, 50th, 75th, 90th, and 95th percentiles were significant histogram parameters between high- and low-grade tumors. The ROC analysis between high- and low-grade tumors showed that the 95th percentile ADC achieved the highest area under curve (AUC) at 0.74. Lymphovascular invasion was associated with the ADC mean, 50th, 75th, 90th, and 95th percentiles, skewness, and kurtosis. Kurtosis achieved the highest AUC at 0.809. Pleural invasion was only associated with skewness, with the AUC of 0.648. ADC histogram analyses on the basis of the entire tumor volume are able to stratify NSCLCs' tumor grade, lymphovascular invasion and pleural invasion.

Apparent diffusion coefficient histogram analysis can evaluate radiation-induced parotid damage and predict late xerostomia degree in nasopharyngeal carcinoma.

PubMed

Zhou, Nan; Guo, Tingting; Zheng, Huanhuan; Pan, Xia; Chu, Chen; Dou, Xin; Li, Ming; Liu, Song; Zhu, Lijing; Liu, Baorui; Chen, Weibo; He, Jian; Yan, Jing; Zhou, Zhengyang; Yang, Xiaofeng

2017-09-19

We investigated apparent diffusion coefficient (ADC) histogram analysis to evaluate radiation-induced parotid damage and predict xerostomia degrees in nasopharyngeal carcinoma (NPC) patients receiving radiotherapy. The imaging of bilateral parotid glands in NPC patients was conducted 2 weeks before radiotherapy (time point 1), one month after radiotherapy (time point 2), and four months after radiotherapy (time point 3). From time point 1 to 2, parotid volume, skewness, and kurtosis decreased ( P < 0.001, = 0.001, and < 0.001, respectively), but all other ADC histogram parameters increased (all P < 0.001, except P = 0.006 for standard deviation [SD]). From time point 2 to 3, parotid volume continued to decrease ( P = 0.022), and SD, 75 th and 90 th percentiles continued to increase ( P = 0.024, 0.010, and 0.006, respectively). Early change rates of parotid ADC mean , ADC min , kurtosis, and 25 th , 50 th , 75 th , 90 th percentiles (from time point 1 to 2) correlated with late parotid atrophy rate (from time point 1 to 3) (all P < 0.05). Multiple linear regression analysis revealed correlations among parotid volume, time point, and ADC histogram parameters. Early mean change rates for bilateral parotid SD and ADC max could predict late xerostomia degrees at seven months after radiotherapy (three months after time point 3) with AUC of 0.781 and 0.818 ( P = 0.014, 0.005, respectively). ADC histogram parameters were reproducible (intraclass correlation coefficient, 0.830 - 0.999). ADC histogram analysis could be used to evaluate radiation-induced parotid damage noninvasively, and predict late xerostomia degrees of NPC patients treated with radiotherapy.

Usefulness of the apparent diffusion coefficient for the evaluation of the white matter to differentiate between glioblastoma and brain metastases.

PubMed

Miquelini, L A; Pérez Akly, M S; Funes, J A; Besada, C H

2016-01-01

To determine whether there are significant differences in the apparent diffusion coefficient (ADC) between the apparently normal peritumor white matter surrounding glioblastomas and that surrounding brain metastases. We retrospectively reviewed 42 patients with histologically confirmed glioblastomas and 42 patients with a single cerebral metastasis. We measured the signal intensity in the apparently normal peritumor white matter and in the abnormal peritumor white matter on the ADC maps. We used mean ADC values in the contralateral occipital white matter as a reference from which to design normalized ADC indices. We compared mean values between the two tumor types. We calculated the area under the receiver operator characteristic curve and estimated the sensitivity and specificity of the measurements taken. Supratentorial lesions and compromise of the corpus callosum were more common in patients with glioblastoma than in patients with brain metastases. The maximum diameter of the enhanced area after injection of a contrast agent was greater in the glioblastomas (p<0.001). The minimum ADC value measured in the apparently normal peritumor white matter was higher for the glioblastomas than for the metastases (p=0.002). Significant differences in the ADC index were found only for the minimum ADC value in apparently normal peritumor white matter. The sensitivity and specificity were less than 70% for all variables analyzed. There are differences in the ADC values of apparently normal peritumor white matter between glioblastomas and cerebral metastases, but the magnitude of these differences is slight and the application of these differences in clinical practice is still limited. Copyright © 2015 SERAM. Published by Elsevier España, S.L.U. All rights reserved.

ADC as a useful diagnostic tool for differentiating benign and malignant vertebral bone marrow lesions and compression fractures: a systematic review and meta-analysis.

PubMed

Suh, Chong Hyun; Yun, Seong Jong; Jin, Wook; Lee, Sun Hwa; Park, So Young; Ryu, Chang-Woo

2018-07-01

To assess the sensitivity and specificity of quantitative assessment of the apparent diffusion coefficient (ADC) for differentiating benign and malignant vertebral bone marrow lesions (BMLs) and compression fractures (CFs) METHODS: An electronic literature search of MEDLINE and EMBASE was conducted. Bivariate modelling and hierarchical summary receiver operating characteristic modelling were performed to evaluate the diagnostic performance of ADC for differentiating vertebral BMLs. Subgroup analysis was performed for differentiating benign and malignant vertebral CFs. Meta-regression analyses according to subject, study and diffusion-weighted imaging (DWI) characteristics were performed. Twelve eligible studies (748 lesions, 661 patients) were included. The ADC exhibited a pooled sensitivity of 0.89 (95% confidence interval [CI] 0.80-0.94) and a pooled specificity of 0.87 (95% CI 0.78-0.93) for differentiating benign and malignant vertebral BMLs. In addition, the pooled sensitivity and specificity for differentiating benign and malignant CFs were 0.92 (95% CI 0.82-0.97) and 0.91 (95% CI 0.87-0.94), respectively. In the meta-regression analysis, the DWI slice thickness was a significant factor affecting heterogeneity (p < 0.01); thinner slice thickness (< 5 mm) showed higher specificity (95%) than thicker slice thickness (81%). Quantitative assessment of ADC is a useful diagnostic tool for differentiating benign and malignant vertebral BMLs and CFs. • Quantitative assessment of ADC is useful in differentiating vertebral BMLs. • Quantitative ADC assessment for BMLs had sensitivity of 89%, specificity of 87%. • Quantitative ADC assessment for CFs had sensitivity of 92%, specificity of 91%. • The specificity is highest (95%) with thinner (< 5 mm) DWI slice thickness.

Evolution of Antibody-Drug Conjugate Tumor Disposition Model to Predict Preclinical Tumor Pharmacokinetics of Trastuzumab-Emtansine (T-DM1).

PubMed

Singh, Aman P; Maass, Katie F; Betts, Alison M; Wittrup, K Dane; Kulkarni, Chethana; King, Lindsay E; Khot, Antari; Shah, Dhaval K

2016-07-01

A mathematical model capable of accurately characterizing intracellular disposition of ADCs is essential for a priori predicting unconjugated drug concentrations inside the tumor. Towards this goal, the objectives of this manuscript were to: (1) evolve previously published cellular disposition model of ADC with more intracellular details to characterize the disposition of T-DM1 in different HER2 expressing cell lines, (2) integrate the improved cellular model with the ADC tumor disposition model to a priori predict DM1 concentrations in a preclinical tumor model, and (3) identify prominent pathways and sensitive parameters associated with intracellular activation of ADCs. The cellular disposition model was augmented by incorporating intracellular ADC degradation and passive diffusion of unconjugated drug across tumor cells. Different biomeasures and chemomeasures for T-DM1, quantified in the companion manuscript, were incorporated into the modified model of ADC to characterize in vitro pharmacokinetics of T-DM1 in three HER2+ cell lines. When the cellular model was integrated with the tumor disposition model, the model was able to a priori predict tumor DM1 concentrations in xenograft mice. Pathway analysis suggested different contribution of antigen-mediated and passive diffusion pathways for intracellular unconjugated drug exposure between in vitro and in vivo systems. Global and local sensitivity analyses revealed that non-specific deconjugation and passive diffusion of the drug across tumor cell membrane are key parameters for drug exposure inside a cell. Finally, a systems pharmacokinetic model for intracellular processing of ADCs has been proposed to highlight our current understanding about the determinants of ADC activation inside a cell.

The performance of PI-RADSv2 and quantitative apparent diffusion coefficient for predicting confirmatory prostate biopsy findings in patients considered for active surveillance of prostate cancer.

PubMed

Nougaret, Stephanie; Robertson, Nicola; Golia Pernicka, Jennifer; Molinari, Nicolas; Hötker, Andreas M; Ehdaie, Behfar; Sala, Evis; Hricak, Hedvig; Vargas, Hebert Alberto

2017-07-01

To assess the performance of the updated Prostate Imaging Reporting and Data System (PI-RADSv2) and the apparent diffusion coefficient (ADC) for predicting confirmatory biopsy results in patients considered for active surveillance of prostate cancer (PCA). IRB-approved, retrospective study of 371 consecutive men with clinically low-risk PCA (initial biopsy Gleason score ≤6, prostate-specific antigen <10 ng/ml, clinical stage ≤T2a) who underwent 3T-prostate MRI before confirmatory biopsy. Two independent radiologists recorded the PI-RADSv2 scores and measured the corresponding ADC values in each patient. A composite score was generated to assess the performance of combining PI-RADSv2 + ADC. PCA was upgraded on confirmatory biopsy in 107/371 (29%) patients. Inter-reader agreement was substantial (PI-RADSv2: k = 0.73; 95% CI [0.66-0.80]; ADC: r = 0.74; 95% CI [0.69-0.79]). Accuracies, sensitivities, specificities, positive predicted value and negative predicted value of PI-RADSv2 were 85, 89, 83, 68, 95 and 78, 82, 76, 58, 91% for ADC. PI-RADSv2 accuracy was significantly higher than that of ADC for predicting biopsy upgrade (p = 0.014). The combined PI-RADSv2 + ADC composite score did not perform better than PI-RADSv2 alone. Obviating biopsy in patients with PI-RADSv2 score ≤3 would have missed Gleason Score upgrade in 12/232 (5%) of patients. PI-RADSv2 was superior to ADC measurements for predicting PCA upgrading on confirmatory biopsy.

Characterizing focal hepatic lesions by free-breathing intravoxel incoherent motion MRI at 3.0 T.

PubMed

Watanabe, Haruo; Kanematsu, Masayuki; Goshima, Satoshi; Kajita, Kimihiro; Kawada, Hiroshi; Noda, Yoshifumi; Tatahashi, Yukichi; Kawai, Nobuyuki; Kondo, Hiroshi; Moriyama, Noriyuki

2014-12-01

Diffusion-weighted (DW) imaging is commonly used to distinguish between benign and malignant liver lesions. To prospectively evaluate the true molecular-diffusion coefficient (D), perfusion-related diffusion coefficient (D*), perfusion fraction (f), and ADC of focal hepatic lesions using a free-breathing intravoxel incoherent motion (IVIM) DW sequence, and to determine if these parameters are useful for characterizing focal hepatic lesions. One hundred and twenty hepatic lesions (34 metastases, 32 hepatocellular carcinoma [HCC], 33 hemangiomas, and 21 liver cysts) in 74 patients were examined. Mean D, D*, f, and ADC values of hepatic lesions were compared among pathologies. ROC curve analyses were performed to assess the performances of D, D*, f, and ADC values for the characterization of liver lesions as benign or malignant. The mean D and ADC values of benign lesions were greater than those of malignant lesions (P < 0.001). Although the mean D and ADC values of liver cysts were greater than those of hemangiomas (P < 0.001), and these values were not significantly different between metastases and HCCs (P = 0.99). Area under the ROC curve for ADC values (0.98) was significantly greater (P = 0.048) than that for D values (0.96) for the differentiation of benign and malignant lesions. Sensitivity and specificity for the detection of malignant lesion were 89% and 98%, respectively, when an ADC cut-off value of 1.40 was applied. D and ADC values have more potential for characterizing focal hepatic lesions than D* or f values, and for the differentiation of malignancy and benignity. © The Foundation Acta Radiologica 2013 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Diffusion-weighted MR imaging: role in the differential diagnosis of breast lesions.

PubMed

Altay, C; Balci, P; Altay, S; Karasu, S; Saydam, S; Canda, T; Dicle, O

2014-01-01

To evaluate the diagnostic value of magnetic resonance diffusion-weighted imaging (DWI) using apparent diffusion coefficient (ADC) values to the characterization of breast lesions and differentiation of benign and malignant lesions. Thirty-seven women (mean age, 38 years) with 37 enrolled in the study. DWI and ADC maps in the axial plane were obtained using a 1.5 Tesla MRI device. Mean ADC measurements were calculated among cysts, normal fibroglandular tissue, benign lesions and malignant lesions were evaluated. Out of 37 women, 4 had normally breast MRI findings. The diagnosis of remaining 33 patients with 37 breast lesions were as follows; malign lesions (n = 23), benign lesions (n = 10) and simple breast cyst (n = 4). The ADC values were as follows (in units of 10(-3) mm2/s): Normal fibroglandular tissue (range: 1.39-2.06; mean: 1.61 ± 0.23), benign breast lesions (range: 1.09-1.76; mean: 1.47 ± 0.25), cyts (range: 2.27-2.46, mean: 2.37 ± 0.07) and malignant breast lesions (range: 0.78-1.26, mean: 0.96 ± 0.25). The mean ADC obtained from malignant breast lesions was statistically different from that observed in benign solid lesions (p < < 0.01) and normal fibroglandular breast tissue (p < 0.01). Furthermore, the mean ADC values of benign breast lesions was not statistically different from cyst (p ≥ 0.01) and normal fibroglandular breast tissue (p ≥ 0.01). A ADC value of 1.1 x 10(-3) mm'/s as a treshold value provided differantiation for malign and benign lesions, with a sensitivity of 91.3% and a specificity of 85.7% compared with conventional breast MRI values. DWI with quantitative ADC measurements is a reliable tool for differentiation of benign and malignant breast lesions.

Can Diffusion-Weighted Imaging and Related Apparent Diffusion Coefficient be a Prognostic Value in Women With Breast Cancer?

PubMed

Rabasco, Paola; Caivano, Rocchina; Simeon, Vittorio; Dinardo, Giuseppina; Lotumolo, Antonella; Gioioso, Matilde; Villonio, Antonio; Iannelli, Giancarlo; D'Antuono, Felice; Zandolino, Alexis; Macarini, Luca; Guglielmi, Giuseppe; Cammarota, Aldo

2017-02-07

To analyze diffusion-weighted imaging (DWI) and the related apparent diffusion coefficient (ADC) in women with breast cancer, correlating these values with the presence at 3 years of distant metastases, and to demonstrate that DWI-Magnetic Resonance Imaging (MRI) and related ADC values may represent a prognostic value in the study of women with breast cancer. Sixty women (aged 45-73 years) affected with breast cancer with a follow-up in 3 years were enrolled. On DWI, we obtained the ADC values, and these were correlated with the clinical condition of patients at 3 years. Moreover, tumour size, lymph node status, and molecular markers, including estrogens receptor, progesterone receptor, Ki-67 index, and human growth factor receptor 2 protein, were correlated with ADC values. This study was approved by the Scientific Committee of our institution. We considered patients with metastasis at 3 years (12 patients - 20%) and without metastasis (48 patients - 80%). The mean ADC value in patients with no metastases at 3 years was 1.06 ± 0.38, while for patients with metastases it was 0.74 ± 0.34 (p = .011). The receiver-operator curve analysis identified a value of 0.75 (<0.75 with risk to develop metastasis) as the best predictive cutoff for ADC values, with the highest sensitivity (81.25%) and higher specificity (66.67%). After regression analysis, ADC value, positivity to estrogen-progestin receptors, and presence of lymph nodes were the only prognostic factors found to be statistically significant. DWI-MRI and related ADC values may represent a prognostic value in women with breast cancer.

Optimization and Clinical Feasibility of Free-breathing Diffusion-weighted Imaging of the Liver: Comparison with Respiratory-Triggered Diffusion-weighted Imaging.

PubMed

Takayama, Yukihisa; Nishie, Akihiro; Asayama, Yoshiki; Ishigami, Kousei; Kakihara, Daisuke; Ushijima, Yasuhiro; Fujita, Nobuhiro; Yoshiura, Takashi; Takemura, Atsushi; Obara, Makoto; Takahara, Taro; Honda, Hiroshi

2015-01-01

We compared the image quality of free-breathing diffusion-weighted imaging (FB-DWI) to that of respiratory-triggered DWI (RT-DWI) after proper optimization. Three healthy subjects were scanned to optimize magnetic resonance (MR) parameters of FB-DWI to improve image quality, including spatial resolution, image noise, and chemical shift artifacts. After this optimization, we scanned 32 patients with liver disease to assess the clinical feasibility of the optimized FB-DWI. Of the 32 patients, 14 had a total of 28 hepatocellular carcinomas (HCCs), four had a total of 15 metastatic liver tumors, and the other 14 had no tumor. Qualitatively, we compared the image quality scores of FB-DWI with those of RT-DWI with the Wilcoxon signed-rank test. Quantitatively, we compared the signal-to-noise ratios (SNRs) of the liver parenchyma, lesion-to-nonlesion contrast-to-noise ratios (CNRs) and apparent diffusion coefficient (ADC) values of the liver parenchyma and liver tumor by the paired t-test. The average scores of image quality for sharpness of liver contour, image noise, and chemical shift artifacts were significantly higher for FB-DWI than RT-DWI (P < 0.05). SNRs, CNRs, and ADC values of the liver parenchyma and tumors did not differ significantly between the 2 DWI methods. Compared with RT-DWI, the optimized FB-DWI provided better spatial resolution, fewer artifacts, and comparable SNRs, lesion-to-nonlesion CNRs, and ADC values.

Bioanalysis of antibody-drug conjugates: American Association of Pharmaceutical Scientists Antibody-Drug Conjugate Working Group position paper.

PubMed

Gorovits, Boris; Alley, Stephen C; Bilic, Sanela; Booth, Brian; Kaur, Surinder; Oldfield, Phillip; Purushothama, Shobha; Rao, Chetana; Shord, Stacy; Siguenza, Patricia

2013-05-01

Antibody-drug conjugates (ADCs) typically consist of a cytotoxic drug covalently bound to an antibody by a linker. These conjugates have the potential to substantially improve efficacy and reduce toxicity compared with cytotoxic small-molecule drugs. Since ADCs are generally complex heterogeneous mixtures of multiple species, these novel therapeutic products present unique bioanalytical challenges. The growing number of ADCs being developed across the industry suggests the need for alignment of the bioanalytical methods or approaches used to assess the multiple species and facilitate consistent interpretation of the bioanalytical data. With limited clinical data, the current strategies that can be used to provide insight into the relationship between the multiple species and the observed clinical safety and efficacy are still evolving. Considerations of the bioanalytical strategies for ADCs based on the current industry practices that take into account the complexity and heterogeneity of ADCs are discussed.

Effects of antibody, drug and linker on the preclinical and clinical toxicities of antibody-drug conjugates

PubMed Central

Donaghy, Heather

2016-01-01

ABSTRACT Antibody-drug conjugates (ADCs) represent a new class of cancer therapeutics. Their design involves a tumor-specific antibody, a linker and a cytotoxic payload. They were designed to allow specific targeting of highly potent cytotoxic agents to tumor cells whilst sparing normal cells. Frequent toxicities that may be driven by any of the components of an ADC have been reported. There are currently more than 50 ADCs in active clinical development, and a further ∼20 that have been discontinued. For this review, the reported toxicities of ADCs were analysed, and the mechanisms for their effects are explored in detail. Methods to reduce toxicities, including dosing strategies and drug design, are discussed. The toxicities reported for active and discontinued drugs are important to drive the rational design and improve the therapeutic index of ADCs of the future. PMID:27045800

Recent advances in the construction of antibody-drug conjugates

NASA Astrophysics Data System (ADS)

Chudasama, Vijay; Maruani, Antoine; Caddick, Stephen

2016-02-01

Antibody-drug conjugates (ADCs) comprise antibodies covalently attached to highly potent drugs using a variety of conjugation technologies. As therapeutics, they combine the exquisite specificity of antibodies, enabling discrimination between healthy and diseased tissue, with the cell-killing ability of cytotoxic drugs. This powerful and exciting class of targeted therapy has shown considerable promise in the treatment of various cancers with two US Food and Drug Administration approved ADCs currently on the market (Adcetris and Kadcyla) and approximately 40 currently undergoing clinical evaluation. However, most of these ADCs exist as heterogeneous mixtures, which can result in a narrow therapeutic window and have major pharmacokinetic implications. In order for ADCs to deliver their full potential, sophisticated site-specific conjugation technologies to connect the drug to the antibody are vital. This Perspective discusses the strategies currently used for the site-specific construction of ADCs and appraises their merits and disadvantages.

Combined diffusion-weighted, blood oxygen level-dependent, and dynamic contrast-enhanced MRI for characterization and differentiation of renal cell carcinoma.

PubMed

Notohamiprodjo, Mike; Staehler, Michael; Steiner, Nicole; Schwab, Felix; Sourbron, Steven P; Michaely, Henrik J; Helck, Andreas D; Reiser, Maximilian F; Nikolaou, Konstantin

2013-06-01

To investigate a multiparametric magnetic resonance imaging (MRI) approach comprising diffusion-weighted imaging (DWI), blood oxygen-dependent (BOLD), and dynamic contrast-enhanced (DCE) MRI for characterization and differentiation of primary renal cell carcinoma (RCC). Fourteen patients with clear-cell carcinoma and four patients with papillary RCC were examined with DWI, BOLD MRI, and DCE MRI at 1.5T. The apparent diffusion coefficient (ADC) was calculated with a monoexponential decay. The spin-dephasing rate R2* was derived from parametric R2* maps. DCE-MRI was analyzed using a two-compartment exchange model allowing separation of perfusion (plasma flow [FP] and plasma volume [VP]), permeability (permeability surface area product [PS]), and extravascular extracellular volume (VE). Statistical analysis was performed with Wilcoxon signed-rank test, Pearson's correlation coefficient, and receiver operating characteristic curve analysis. Clear-cell RCC showed higher ADC and lower R2* compared to papillary subtypes, but differences were not significant. FP of clear-cell subtypes was significantly higher than in papillary RCC. Perfusion parameters showed moderate but significant inverse correlation with R2*. VE showed moderate inverse correlation with ADC. Fp and Vp showed best sensitivity for histological differentiation. Multiparametric MRI comprising DWI, BOLD, and DCE MRI is feasible for assessment of primary RCC. BOLD moderately correlates to DCE MRI-derived perfusion. ADC shows moderate correlation to the extracellular volume, but does not correlate to tumor oxygenation or perfusion. In this preliminary study DCE-MRI appeared superior to BOLD and DWI for histological differentiation. Copyright © 2013 AUR. Published by Elsevier Inc. All rights reserved.

Fast data transmission in dynamic data acquisition system for plasma diagnostics

NASA Astrophysics Data System (ADS)

Byszuk, Adrian; Poźniak, Krzysztof; Zabołotny, Wojciech M.; Kasprowicz, Grzegorz; Wojeński, Andrzej; Cieszewski, Radosław; Juszczyk, Bartłomiej; Kolasiński, Piotr; Zienkiewicz, Paweł; Chernyshova, Maryna; Czarski, Tomasz

2014-11-01

This paper describes architecture of a new data acquisition system (DAQ) targeted mainly at plasma diagnostic experiments. Modular architecture, in combination with selected hardware components, allows for straightforward reconfiguration of the whole system, both offline and online. Main emphasis will be put into the implementation of data transmission subsystem in said system. One of the biggest advantages of described system is modular architecture with well defined boundaries between main components: analog frontend (AFE), digital backplane and acquisition/control software. Usage of a FPGA chips allows for a high flexibility in design of analog frontends, including ADC <--> FPGA interface. Data transmission between backplane boards and user software was accomplished with the use of industry-standard PCI Express (PCIe) technology. PCIe implementation includes both FPGA firmware and Linux device driver. High flexibility of PCIe connections was accomplished due to use of configurable PCIe switch. Whenever it's possible, described DAQ system tries to make use of standard off-the-shelf (OTF) components, including typical x86 CPU & motherboard (acting as PCIe controller) and cabling.

Arithmetic Data Cube as a Data Intensive Benchmark

NASA Technical Reports Server (NTRS)

Frumkin, Michael A.; Shabano, Leonid

2003-01-01

Data movement across computational grids and across memory hierarchy of individual grid machines is known to be a limiting factor for application involving large data sets. In this paper we introduce the Data Cube Operator on an Arithmetic Data Set which we call Arithmetic Data Cube (ADC). We propose to use the ADC to benchmark grid capabilities to handle large distributed data sets. The ADC stresses all levels of grid memory by producing 2d views of an Arithmetic Data Set of d-tuples described by a small number of parameters. We control data intensity of the ADC by controlling the sizes of the views through choice of the tuple parameters.

Use of quantitative diffusion-weighted magnetic resonance imaging to predict human papilloma virus status in patients with oropharyngeal squamous cell carcinoma.

PubMed

Nakahira, Mitsuhiko; Saito, Naoko; Yamaguchi, Hiroshi; Kuba, Kiyomi; Sugasawa, Masashi

2014-05-01

Although identification of human papilloma virus (HPV) status in oropharyngeal squamous cell carcinoma (OPSCC) is essential in predicting treatment response, no imaging modality can currently determine whether a tumor is HPV-related. In this retrospective study, 26 patients with OPSCC confined to the lateral wall or the base of tongue underwent neck magnetic resonance imaging, using T1-, T2- and diffusion-weighted imaging (DWI). Apparent diffusion coefficients (ADCs) in a region of interest covering the largest available primary tumor area of OPSCC on a single slice of the ADC map were calculated using two b values (0 and 1,000 s/mm(2)). Mean and minimum ADCs were compared with HPV status, using p16 immunohistochemistry as a surrogate marker for HPV infection. Mean and minimum ADCs for HPV(+) OPSCC were significantly lower than those for HPV(-) OPSCC. A cut-off value of mean ADC for HPV(+) OPSCC of 1.027 × 10(-3) mm(2)/s yielded sensitivity and specificity of 83.33 and 78.57%, respectively. In conclusion, the present study indicates that ADC could be used to predict HPV status in patients with OPSCC.

Multiparametric MRI Apparent Diffusion Coefficient (ADC) Accuracy in Diagnosing Clinically Significant Prostate Cancer.

PubMed

Pepe, Pietro; D'Urso, Davide; Garufi, Antonio; Priolo, Giandomenico; Pennisi, Michele; Russo, Giorgio; Sabini, Maria Gabriella; Valastro, Lucia Maria; Galia, Antonio; Fraggetta, Filippo

2017-01-01

To evaluate the accuracy of multiparametric magnetic resonance imaging apparent diffusion coefficient (mpMRI ADC) in the diagnosis of clinically significant prostate cancer (PCa). From January 2016 to December 2016, 44 patients who underwent radical prostatectomy for PCa and mpMRI lesions suggestive of cancer were retrospectively evaluated at definitive specimen. The accuracy of suspicious mpMRI prostate imaging reporting and data system (PI-RADS ≥3) vs. ADC values in the diagnosis of Gleason score ≥7 was evaluated. Receiver operating characteristics (ROC) curve analysis gave back an ADC threshold of 0.747×10 -3 mm 2 /s to separate between Gleason Score 6 and ≥7. The diagnostic accuracy of ADC value (cut-off 0.747×10 -3 mm 2 /s) vs. PI-RADS score ≥3 in diagnosing PCa with Gleason score ≥7 was equal to 84% vs. 63.6% with an area under the curve (AUC) ROC of 0.81 vs. 0.71, respectively. ADC evaluation could support clinicians in decision making of patients with PI-RADS score <3 at risk for PCa. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Reticular Appearance on Gadolinium-enhanced T1- and Diffusion-weighted MRI, and Low Apparent Diffusion Coefficient Values in Microcystic Meningioma Cysts.

PubMed

Terada, Yukinori; Toda, Hiroki; Okumura, Ryosuke; Ikeda, Naokado; Yuba, Yoshiaki; Katayama, Toshiro; Iwasaki, Koichi

2018-03-01

Microcystic meningioma, a rare meningioma subtype, can present diagnostic difficulty. We aimed to investigate the historadiological properties of microcystic meningioma using conventional magnetic resonance imaging (MRI) and diffusion-weighted imaging (DWI) analysis. We retrospectively analyzed conventional MRI and DWI results of six microcystic meningioma cases by examining their appearance and determining their apparent diffusion coefficient (ADC) values. The ADC values of the intratumoral components were normalized with ADC values of the cerebrospinal fluid in the lateral ventricle (ADC ratios). As cystic formations are frequently associated with microcystic meningiomas, their MRI characteristics were compared with the imaging data from 11 cystic meningiomas of non-microcystic subtypes. We found that cysts in microcystic meningioma tended to have a reticular appearance on DWI, as they did on gadolinium-enhanced T1-weighted imaging. Additionally, these reticular cysts had significantly lower ADC ratios than microcystic non-reticular and non-microcystic cysts. These DWI characteristics likely reflect the histological properties of microcystic meningioma. A reticular appearance on gadolinium-enhanced T1-weighted MRI and DWI, and cyst formation with relatively low ADC values can be diagnostic markers of microcystic meningiomas.

TU-AB-BRA-07: Distortion-Free 3D Diffusion MRI On An MRI-Guided Radiotherapy System for Longitudinal Tumor Response Assessment

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

Gao, Y; Yang, Y; Rangwala, N

Purpose: To develop a reliable, 3D distortion-free diffusion MRI technique for longitudinal tumor response assessment and MRI-guided adaptive radiotherapy(RT). Methods: A diffusion prepared 3D turbo spin echo readout (DP-TSE) sequence was developed and compared with the conventional diffusion-weighted single-shot echo-planar-imaging (DW-ssEPI) sequence in a commercially available diffusion phantom, and one head-and-neck and one brain cancer patient on an MRI-guided RT system (ViewRay). In phantom study, the geometric fidelity was quantified as the ratio between the left-right (RL) and anterior-posterior (AP) dimension. Ten slices were measured on DP-TSE, DW-ssEPI and standard TSE images where the later was used as the geometricmore » reference. ADC accuracy was verified at both 0°C (reference ADC available) and room temperature with a range of diffusivity between 0.35 and 2.0*10{sup −3}mm{sup 2}/s. The ADC reproducibility was assessed based on 8 room-temperature measurements on 6 different days. In the pilot single-slice in-vivo study, CT images were used as the geometric reference, and ADC maps from both diffusion sequences were compared. Results: Distortion and susceptive-related artifact were severe in DW-ssEPI, with significantly lower RL/AP ratio (0.9579±0.0163) than DP-TSE (0.9990±0.0031) and TSE (0.9995±0.0031). ADCs from the two diffusion sequences both matched well with the vendor-provided values at 0°C; however DW-ssEPI fails to provide accurate ADC for high diffusivity vials at room temperature due to high noise level (10 times higher than DP-TSE). The DP-TSE sequence had excellent ADC reproducibility with <4% ADC variation among 8 separate measurements. In patient study, DP-TSE exhibited substantially improved geometric reliability. ROI analysis in ADC maps generated from DP-TSE and DW-ssEPI showed <5% difference where high b-value images were excluded from the latter approach due to excessive noise level. Conclusion: A diffusion MRI sequence with excellent geometric fidelity, accurate and highly reproducible ADC measurements was proposed for longitudinal tumor response assessment using an MRI-guided RT system. Yu Gao acknowledges research support from ViewRay.« less

GET: A generic electronics system for TPCs and nuclear physics instrumentation

NASA Astrophysics Data System (ADS)

Pollacco, E. C.; Grinyer, G. F.; Abu-Nimeh, F.; Ahn, T.; Anvar, S.; Arokiaraj, A.; Ayyad, Y.; Baba, H.; Babo, M.; Baron, P.; Bazin, D.; Beceiro-Novo, S.; Belkhiria, C.; Blaizot, M.; Blank, B.; Bradt, J.; Cardella, G.; Carpenter, L.; Ceruti, S.; De Filippo, E.; Delagnes, E.; De Luca, S.; De Witte, H.; Druillole, F.; Duclos, B.; Favela, F.; Fritsch, A.; Giovinazzo, J.; Gueye, C.; Isobe, T.; Hellmuth, P.; Huss, C.; Lachacinski, B.; Laffoley, A. T.; Lebertre, G.; Legeard, L.; Lynch, W. G.; Marchi, T.; Martina, L.; Maugeais, C.; Mittig, W.; Nalpas, L.; Pagano, E. V.; Pancin, J.; Poleshchuk, O.; Pedroza, J. L.; Pibernat, J.; Primault, S.; Raabe, R.; Raine, B.; Rebii, A.; Renaud, M.; Roger, T.; Roussel-Chomaz, P.; Russotto, P.; Saccà, G.; Saillant, F.; Sizun, P.; Suzuki, D.; Swartz, J. A.; Tizon, A.; Usher, N.; Wittwer, G.; Yang, J. C.

2018-04-01

General Electronics for TPCs (GET) is a generic, reconfigurable and comprehensive electronics and data-acquisition system for nuclear physics instrumentation of up to 33792 channels. The system consists of a custom-designed ASIC for signal processing, front-end cards that each house 4 ASIC chips and digitize the data in parallel through 12-bit ADCs, concentration boards to read and process the digital data from up to 16 ASICs, a 3-level trigger and master clock module to trigger the system and synchronize the data, as well as all of the associated firmware, communication and data-acquisition software. An overview of the system including its specifications and measured performances are presented.

Impact of automated dispensing cabinets on medication selection and preparation error rates in an emergency department: a prospective and direct observational before-and-after study.

PubMed

Fanning, Laura; Jones, Nick; Manias, Elizabeth

2016-04-01

The implementation of automated dispensing cabinets (ADCs) in healthcare facilities appears to be increasing, in particular within Australian hospital emergency departments (EDs). While the investment in ADCs is on the increase, no studies have specifically investigated the impacts of ADCs on medication selection and preparation error rates in EDs. Our aim was to assess the impact of ADCs on medication selection and preparation error rates in an ED of a tertiary teaching hospital. Pre intervention and post intervention study involving direct observations of nurses completing medication selection and preparation activities before and after the implementation of ADCs in the original and new emergency departments within a 377-bed tertiary teaching hospital in Australia. Medication selection and preparation error rates were calculated and compared between these two periods. Secondary end points included the impact on medication error type and severity. A total of 2087 medication selection and preparations were observed among 808 patients pre and post intervention. Implementation of ADCs in the new ED resulted in a 64.7% (1.96% versus 0.69%, respectively, P = 0.017) reduction in medication selection and preparation errors. All medication error types were reduced in the post intervention study period. There was an insignificant impact on medication error severity as all errors detected were categorised as minor. The implementation of ADCs could reduce medication selection and preparation errors and improve medication safety in an ED setting. © 2015 John Wiley & Sons, Ltd.

Histogram Analysis of Diffusion Weighted Imaging at 3T is Useful for Prediction of Lymphatic Metastatic Spread, Proliferative Activity, and Cellularity in Thyroid Cancer.

PubMed

Schob, Stefan; Meyer, Hans Jonas; Dieckow, Julia; Pervinder, Bhogal; Pazaitis, Nikolaos; Höhn, Anne Kathrin; Garnov, Nikita; Horvath-Rizea, Diana; Hoffmann, Karl-Titus; Surov, Alexey

2017-04-12

Pre-surgical diffusion weighted imaging (DWI) is increasingly important in the context of thyroid cancer for identification of the optimal treatment strategy. It has exemplarily been shown that DWI at 3T can distinguish undifferentiated from well-differentiated thyroid carcinoma, which has decisive implications for the magnitude of surgery. This study used DWI histogram analysis of whole tumor apparent diffusion coefficient (ADC) maps. The primary aim was to discriminate thyroid carcinomas which had already gained the capacity to metastasize lymphatically from those not yet being able to spread via the lymphatic system. The secondary aim was to reflect prognostically important tumor-biological features like cellularity and proliferative activity with ADC histogram analysis. Fifteen patients with follicular-cell derived thyroid cancer were enrolled. Lymph node status, extent of infiltration of surrounding tissue, and Ki-67 and p53 expression were assessed in these patients. DWI was obtained in a 3T system using b values of 0, 400, and 800 s/mm². Whole tumor ADC volumes were analyzed using a histogram-based approach. Several ADC parameters showed significant correlations with immunohistopathological parameters. Most importantly, ADC histogram skewness and ADC histogram kurtosis were able to differentiate between nodal negative and nodal positive thyroid carcinoma. histogram analysis of whole ADC tumor volumes has the potential to provide valuable information on tumor biology in thyroid carcinoma. However, further studies are warranted.

Histogram Analysis of Diffusion Weighted Imaging at 3T is Useful for Prediction of Lymphatic Metastatic Spread, Proliferative Activity, and Cellularity in Thyroid Cancer

PubMed Central

Schob, Stefan; Meyer, Hans Jonas; Dieckow, Julia; Pervinder, Bhogal; Pazaitis, Nikolaos; Höhn, Anne Kathrin; Garnov, Nikita; Horvath-Rizea, Diana; Hoffmann, Karl-Titus; Surov, Alexey

2017-01-01

Pre-surgical diffusion weighted imaging (DWI) is increasingly important in the context of thyroid cancer for identification of the optimal treatment strategy. It has exemplarily been shown that DWI at 3T can distinguish undifferentiated from well-differentiated thyroid carcinoma, which has decisive implications for the magnitude of surgery. This study used DWI histogram analysis of whole tumor apparent diffusion coefficient (ADC) maps. The primary aim was to discriminate thyroid carcinomas which had already gained the capacity to metastasize lymphatically from those not yet being able to spread via the lymphatic system. The secondary aim was to reflect prognostically important tumor-biological features like cellularity and proliferative activity with ADC histogram analysis. Fifteen patients with follicular-cell derived thyroid cancer were enrolled. Lymph node status, extent of infiltration of surrounding tissue, and Ki-67 and p53 expression were assessed in these patients. DWI was obtained in a 3T system using b values of 0, 400, and 800 s/mm2. Whole tumor ADC volumes were analyzed using a histogram-based approach. Several ADC parameters showed significant correlations with immunohistopathological parameters. Most importantly, ADC histogram skewness and ADC histogram kurtosis were able to differentiate between nodal negative and nodal positive thyroid carcinoma. Conclusions: histogram analysis of whole ADC tumor volumes has the potential to provide valuable information on tumor biology in thyroid carcinoma. However, further studies are warranted. PMID:28417929

The correlation between biological activity and diffusion-weighted MR imaging and ADC value in cases with prostate cancer.

PubMed

Sokmen, Bedriye Koyuncu; Sokmen, Dogukan; Ucar, Nese; Ozkurt, Huseyin; Simsek, Abdulmuttalip

2017-12-31

Firstly, we aimed to investigate the correlation among dynamic contrasted magnetic resonance (MR) images, diffusion-weighted MR images, and apparent diffusion coefficent (ADC) values in patients with prostate cancer. Secondly, we aimed to investigate the roles of these variables on clinical risk classification and the biological behavior of the prostate cancer. A total of sixty with prostatic adenocarcinoma patients diagnosed between January 2011 and May 2013 were retrospectively included in the study. Risk classification of patients were evaluated as low-risk (Group 1) (n = 20) (Stage T1c-T2a, PSA < 10 ng/ml, Gleason Score < 7), moderate-risk (Group 2) (n = 18) (Stage T1b-T2c, PSA = 10-20 ng/ml, Gleason Score = 7) and high-risk (Group 3) (n = 22) (Stage > T3a, PSA > 20 ng/ml, Gleason Score > 7). Diffusion-weighted MR images, dynamic contrasted MR images, and ADC values of the prostates were correlated. ADC values of the cases in Group 3 were lower than those of the other groups (p < 0.001). ADC values of the areas without malignancy did not differ significantly between groups (p > 0.05). Biological activity of the tumor tissue was determined by GS, while a negative correlation was observed between GSs and ADC values of the patients, (p < 0.001). In tumors with higher Gleason scores, lower ADC values were obtained. These measured values can play a role in the noninvasive determination of the cellularity of the tumoral mass.

Assessing the inter-observer variability of Computer-Aided Nodule Assessment and Risk Yield (CANARY) to characterize lung adenocarcinomas.

PubMed

Nakajima, Erica C; Frankland, Michael P; Johnson, Tucker F; Antic, Sanja L; Chen, Heidi; Chen, Sheau-Chiann; Karwoski, Ronald A; Walker, Ronald; Landman, Bennett A; Clay, Ryan D; Bartholmai, Brian J; Rajagopalan, Srinivasan; Peikert, Tobias; Massion, Pierre P; Maldonado, Fabien

2018-01-01

Lung adenocarcinoma (ADC), the most common lung cancer type, is recognized increasingly as a disease spectrum. To guide individualized patient care, a non-invasive means of distinguishing indolent from aggressive ADC subtypes is needed urgently. Computer-Aided Nodule Assessment and Risk Yield (CANARY) is a novel computed tomography (CT) tool that characterizes early ADCs by detecting nine distinct CT voxel classes, representing a spectrum of lepidic to invasive growth, within an ADC. CANARY characterization has been shown to correlate with ADC histology and patient outcomes. This study evaluated the inter-observer variability of CANARY analysis. Three novice observers segmented and analyzed independently 95 biopsy-confirmed lung ADCs from Vanderbilt University Medical Center/Nashville Veterans Administration Tennessee Valley Healthcare system (VUMC/TVHS) and the Mayo Clinic (Mayo). Inter-observer variability was measured using intra-class correlation coefficient (ICC). The average ICC for all CANARY classes was 0.828 (95% CI 0.76, 0.895) for the VUMC/TVHS cohort, and 0.852 (95% CI 0.804, 0.901) for the Mayo cohort. The most invasive voxel classes had the highest ICC values. To determine whether nodule size influenced inter-observer variability, an additional cohort of 49 sub-centimeter nodules from Mayo were also segmented by three observers, with similar ICC results. Our study demonstrates that CANARY ADC classification between novice CANARY users has an acceptably low degree of variability, and supports the further development of CANARY for clinical application.

Diffusion radiomics analysis of intratumoral heterogeneity in a murine prostate cancer model following radiotherapy: Pixelwise correlation with histology.

PubMed

Lin, Yu-Chun; Lin, Gigin; Hong, Ji-Hong; Lin, Yi-Ping; Chen, Fang-Hsin; Ng, Shu-Hang; Wang, Chun-Chieh

2017-08-01

To investigate the biological meaning of apparent diffusion coefficient (ADC) values in tumors following radiotherapy. Five mice bearing TRAMP-C1 tumor were half-irradiated with a dose of 15 Gy. Diffusion-weighted images, using multiple b-values from 0 to 3000 s/mm 2 , were acquired at 7T on day 6. ADC values calculated by a two-point estimate and monoexponential fitting of signal decay were compared between the irradiated and nonirradiated regions of the tumor. Pixelwise ADC maps were correlated with histological metrics including nuclear counts, nuclear sizes, nuclear spaces, cytoplasmic spaces, and extracellular spaces. As compared with the nonirradiated region, the irradiated region exhibited significant increases in ADC, extracellular space, and nuclear size, and a significant decrease in nuclear counts (P < 0.001 for all). Optimal ADC to differentiate the irradiated from nonirradiated regions was achieved at a b-value of 800 s/mm 2 by the two-point method and monoexponential curve fitting. ADC positively correlated with extracellular spaces (r = 0.74) and nuclear sizes (r = 0.72), and negatively correlated with nuclear counts (r = -0.82, P < 0.001 for all). As a radiomic biomarker, ADC maps correlating with histological metrics pixelwise could be a means of evaluating tumor heterogeneity and responses to radiotherapy. 1 Technical Efficacy: Stage 2 J. MAGN. RESON. IMAGING 2017;46:483-489. © 2017 International Society for Magnetic Resonance in Medicine.

Ocular Adverse Events Associated with Antibody–Drug Conjugates in Human Clinical Trials

PubMed Central

Miller, Paul E.; Mannis, Mark J.

2015-01-01

Abstract This article reviews ocular adverse events (AEs) reported in association with administration of antibody–drug conjugates (ADCs) in human clinical trials. References reporting ocular toxicity or AEs associated with ADCs were collected using online publication searches. Articles, abstracts, or citations were included if they cited ocular toxicities or vision-impairing AEs with a confirmed or suspected association with ADC administration. Twenty-two references were found citing ocular or vision-impairing AEs in association with ADC administration. All references reported use of ADCs in human clinical trials for treatment of various malignancies. The molecular target and cytotoxic agent varied depending on the ADC used. Ocular AEs affected a diversity of ocular tissues. The most commonly reported AEs involved the ocular surface and included blurred vision, dry eye, and corneal abnormalities (including microcystic corneal disease). Most ocular AEs were not severe (≤ grade 2) or dose limiting. Clinical outcomes were not consistently reported, but when specified, most AEs improved or resolved with cessation of treatment or with ameliorative therapy. A diverse range of ocular AEs are reported in association with administration of ADCs for the treatment of cancer. The toxicologic mechanism(s) and pathogenesis of such events are not well understood, but most are mild in severity and reversible. Drug development and medical professionals should be aware of the clinical features of these events to facilitate early recognition and intervention in the assessment of preclinical development programs and in human clinical trials. PMID:26539624

SU-F-303-13: Initial Evaluation of Four Dimensional Diffusion- Weighted MRI (4D-DWI) and Its Effect On Apparent Diffusion Coefficient (ADC) Measurement

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

Liu, Y; Yin, F; Czito, B

2015-06-15

Purpose: Diffusion-weighted imaging(DWI) has been shown to have superior tumor-to-tissue contrast for cancer detection.This study aims at developing and evaluating a four dimensional DWI(4D-DWI) technique using retrospective sorting method for imaging respiratory motion for radiotherapy planning,and evaluate its effect on Apparent Diffusion Coefficient(ADC) measurement. Materials/Methods: Image acquisition was performed by repeatedly imaging a volume of interest using a multi-slice single-shot 2D-DWI sequence in the axial planes and cine MRI(served as reference) using FIESTA sequence.Each 2D-DWI image were acquired in xyz-diffusion-directions with a high b-value(b=500s/mm2).The respiratory motion was simultaneously recorded using bellows.Retrospective sorting was applied in each direction to reconstruct 4D-DWI.Themore » technique was evaluated using a computer simulated 4D-digital human phantom(XCAT),a motion phantom and a healthy volunteer under an IRB-approved study.Motion trajectories of regions-of-interests(ROI) were extracted from 4D-DWI and compared with reference.The mean motion trajectory amplitude differences(D) between the two was calculated.To quantitatively analyze the motion artifacts,XCAT were controlled to simulate regular motion and the motions of 10 liver cancer patients.4D-DWI,free-breathing DWI(FB- DWI) were reconstructed.Tumor volume difference(VD) of each phase of 4D-DWI and FB-DWI from the input static tumor were calculated.Furthermore, ADC was measured for each phase of 4D-DWI and FB-DWI data,and mean tumor ADC values(M-ADC) were calculated.Mean M-ADC over all 4D-DWI phases was compared with M-ADC calculated from FB-DWI. Results: 4D-DWI of XCAT,the motion phantom and the healthy volunteer demonstrated the respiratory motion clearly.ROI D values were 1.9mm,1.7mm and 2.0mm,respectively.For motion artifacts analysis,XCAT 4D-DWI images show much less motion artifacts compare to FB-DWI.Mean VD for 4D-WDI and FB-DWI were 8.5±1.4% and 108±15%,respectively.Mean M-ADC for ADC measured from 4D-DWI and M-ADC measured from FB-DWI were (2.29±0.04)*0.001*mm2/s and (3.80±0.01)*0.001*mm2/s,respectively.ADC value ground-truth is 2.24*0.001*mm2/s from the input of the simulation. Conclusion: A respiratory correlated 4D-DWI technique has been initially evaluated in phantoms and a human subject.Comparing to free breathing DWI,4D-DWI can lead to more accurate measurement of ADC.« less

A CMOS Imager with Focal Plane Compression using Predictive Coding

NASA Technical Reports Server (NTRS)

Leon-Salas, Walter D.; Balkir, Sina; Sayood, Khalid; Schemm, Nathan; Hoffman, Michael W.

2007-01-01

This paper presents a CMOS image sensor with focal-plane compression. The design has a column-level architecture and it is based on predictive coding techniques for image decorrelation. The prediction operations are performed in the analog domain to avoid quantization noise and to decrease the area complexity of the circuit, The prediction residuals are quantized and encoded by a joint quantizer/coder circuit. To save area resources, the joint quantizerlcoder circuit exploits common circuitry between a single-slope analog-to-digital converter (ADC) and a Golomb-Rice entropy coder. This combination of ADC and encoder allows the integration of the entropy coder at the column level. A prototype chip was fabricated in a 0.35 pm CMOS process. The output of the chip is a compressed bit stream. The test chip occupies a silicon area of 2.60 mm x 5.96 mm which includes an 80 X 44 APS array. Tests of the fabricated chip demonstrate the validity of the design.

The BGO Calorimeter of BGO-OD Experiment

NASA Astrophysics Data System (ADS)

Bantes, B.; Bayadilov, D.; Beck, R.; Becker, M.; Bella, A.; Bielefeldt, P.; Bieling, J.; Bleckwenn, M.; Böse, S.; Braghieri, A.; Brinkmann, K.-Th; Burdeynyi, D.; Curciarello, F.; De Leo, V.; Di Salvo, R.; Dutz, H.; Elsner, D.; Fantini, A.; Freyermuth, O.; Friedrich, S.; Frommberger, F.; Ganenko, V.; Geffers, D.; Gervino, G.; Ghio, F.; Giardina, G.; Girolami, B.; Glazier, D.; Goertz, S.; Gridnev, A.; Gutz, E.; Hammann, D.; Hannappel, J.; Hartmann, P.-F.; Hillert, W.; Ignatov, A.; Jahn, R.; Joosten, R.; Jude, T. C.; Klein, F.; Koop, K.; Krusche, B.; Lapik, A.; Levi Sandri, P.; Lopatin, I.; Mandaglio, G.; Mei, P.; Messi, F.; Messi, R.; Metag, V.; Moricciani, D.; Nanova, M.; Nedorezov, V.; Novinskiy, D.; Pedroni, P.; Romaniuk, M.; Rostomyan, T.; Rudnev, N.; Schaerf, C.; Scheluchin, G.; Schmieden, H.; Sumachev, V.; Tarakanov, V.; Vegna, V.; Walther, D.; Watts, D.; Zaunick, H.-G.; Zimmermann, T.

2015-02-01

The BGO Rugby Ball is a large solid angle electromagnetic calorimeter now installed in the ELSA Facility in Bonn. The BGO is operating in the BGO-OD experiment aiming to study meson photoproduction off proton and neutron induced by a Bremsstrahlung polarized gamma beam of energies from 0.2 to 3.2 GeV and an intensity of 5 × 107 photons per second. The scintillating material characteristics and the photomultiplier read-out make this detector particularly suited for the detection of medium energy photons and electrons with very good energy resolution. The detector has been equipped with a new electronics read-out system, consisting of 30 sampling ADC Wie-Ne-R modules which perform the off-line reconstruction of the signal start-time allowing for a good timing resolution. Performances in linearity, resolution and time response have been carefully tested at the Beam Test Facility of the INFN National Laboratories in Frascati by using a matrix of 7 BGO crystals coupled to photomultipliers and equipped with the Wie-Ne-R sampling ADCs.

SU-E-T-76: Comparing Homogeneity Between Gafchromic Film EBT2 and EBT3

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

Mizuno, H; Sumida, I; Ogawa, K

2014-06-01

Purpose: We found out that homogeneity of EBT2 was different among lot numbers in previous study. Variation in local homogeneity of EBT3 among several lot numbers has not been reported. In this study, we investigated film homogeneity of Gafcrhomic EBT3 films compared with EBT2 films. Methods: All sheets from five lots were cut into 12 pieces to investigate film homogeneity, and were irradiated at 0.5, 2, and 3 Gy. To investigate intra- and inter-sheet uniformity, five sheets from five lots were exposed to 2 Gy: intra-sheet uniformity was evaluated by the coefficient of variation of homogeneity for all pieces ofmore » a single sheet, and inter-sheet uniformity was evaluated by the coefficient of variation of homogeneity among the same piece numbers in the five sheets. To investigate the difference of ADC value in various doses, a single sheet from each of five lots was irradiated at 0.5 Gy and 3 Gy in addition to 2 Gy. A scan resolution of 72 dots per inch (dpi) and color depth of 48-bit RGB were used. Films were analyzed by the inhouse software; Average of ADC value in center ROI and profile X and Y axis were measured. Results and Conclusion: Intra-sheet uniformity of non-irradiated EBT2 films were ranged from 0.1% to 0.4%, however that of irradiated EBT2 films were ranged from 0.2% to 1.5%. On the other hand, intra-sheet uniformity of irradiated and non-irradiated EBT3 films were from 0.2% to 0.6%. Inter-sheet uniformity of all films were less than 0.5%. It was interesting point that homogeneity of EBT3 between no-irradiated and irradiated films were similar value, whereas EBT2 had dose dependence of homogeneity in ADC value evaluation. These results suggested that EBT3 homogeneity was corrected by this feature.« less

Histogram analysis of ADC in brain tumor patients

NASA Astrophysics Data System (ADS)

Banerjee, Debrup; Wang, Jihong; Li, Jiang

2011-03-01

At various stage of progression, most brain tumors are not homogenous. In this presentation, we retrospectively studied the distribution of ADC values inside tumor volume during the course of tumor treatment and progression for a selective group of patients who underwent an anti-VEGF trial. Complete MRI studies were obtained for this selected group of patients including pre- and multiple follow-up, post-treatment imaging studies. In each MRI imaging study, multiple scan series were obtained as a standard protocol which includes T1, T2, T1-post contrast, FLAIR and DTI derived images (ADC, FA etc.) for each visit. All scan series (T1, T2, FLAIR, post-contrast T1) were registered to the corresponding DTI scan at patient's first visit. Conventionally, hyper-intensity regions on T1-post contrast images are believed to represent the core tumor region while regions highlighted by FLAIR may overestimate tumor size. Thus we annotated tumor regions on the T1-post contrast scans and ADC intensity values for pixels were extracted inside tumor regions as defined on T1-post scans. We fit a mixture Gaussian (MG) model for the extracted pixels using the Expectation-Maximization (EM) algorithm, which produced a set of parameters (mean, various and mixture coefficients) for the MG model. This procedure was performed for each visits resulting in a series of GM parameters. We studied the parameters fitted for ADC and see if they can be used as indicators for tumor progression. Additionally, we studied the ADC characteristics in the peri-tumoral region as identified by hyper-intensity on FLAIR scans. The results show that ADC histogram analysis of the tumor region supports the two compartment model that suggests the low ADC value subregion corresponding to densely packed cancer cell while the higher ADC value region corresponding to a mixture of viable and necrotic cells with superimposed edema. Careful studies of the composition and relative volume of the two compartments in tumor region may provide some insights in the early assessment of tumor response to therapy for recurrence brain cancer patients.

DWI in Pediatric Small-Bowel Crohn Disease: Are Apparent Diffusion Coefficients Surrogates for Disease Activity in Patients Receiving Infliximab Therapy?

PubMed

Dillman, Jonathan R; Smith, Ethan A; Sanchez, Ramon; Adler, Jeremy; Fazeli, Soudabeh; Zhang, Bin; Davenport, Matthew S

2016-11-01

The purpose of this study was to determine prospectively whether bowel wall apparent diffusion coefficient (ADC) measurements can be used to monitor treatment response to infliximab therapy in the setting of pediatric small-bowel Crohn disease. Twenty-eight pediatric subjects with newly diagnosed biopsy-proven Crohn disease of the distal or terminal ileum treated with infliximab were enrolled. Subjects underwent MR enterography at baseline, 1 month after therapy, and 6 months after therapy. Imaging features were documented, including bowel wall ADC and arterial or enteric phase contrast-enhanced signal intensity normalized to that of unenhanced imaging. A linear mixed model assessed the relationship between ADC and time; patient age and sex and azathioprine combination therapy were covariates. The diagnostic performance (with 95% CIs) of an increase in bowel wall ADC of 20% or more for identifying response to infliximab was calculated using a decrease in normalized contrast-enhanced bowel wall signal intensity of 20% or more as the reference standard. Bowel wall ADC increased over time (mean [± SD], 1180 ± 200 × 10 -6 mm 2 /s at baseline, 1420 ± 420 × 10 -6 mm 2 /s at 1 month, and 1450 ± 450 × 10 -6 mm 2 /s at 6 months; p = 0.0003); azathioprine therapy modulated this rate of change (p = 0.003). There was a statistically significant negative correlation between change in ADC and change in normalized contrast-enhanced signal intensity over time (ρ = -0.36; p < 0.001). The diagnostic performance of change in ADC for identifying response to infliximab therapy was sensitivity of 0.58 (95% CI, 0.34-0.80), specificity of 0.52 (95% CI, 0.31-0.72), positive predictive value of 0.48 (95% CI, 0.27-0.69), and negative predictive value of 0.62 (95% CI, 0.38-0.82). Bowel wall ADC increases over time in pediatric subjects receiving infliximab, but the diagnostic performance of ADC is likely insufficient for reliable treatment monitoring.

SU-F-T-347: An Absolute Dose-Volume Constraint Based Deterministic Optimization Framework for Multi-Co60 Source Focused Radiotherapy

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

Liang, B; Liu, B; Li, Y

2016-06-15

Purpose: Treatment plan optimization in multi-Co60 source focused radiotherapy with multiple isocenters is challenging, because dose distribution is normalized to maximum dose during optimization and evaluation. The objective functions are traditionally defined based on relative dosimetric distribution. This study presents an alternative absolute dose-volume constraint (ADC) based deterministic optimization framework (ADC-DOF). Methods: The initial isocenters are placed on the eroded target surface. Collimator size is chosen based on the area of 2D contour on corresponding axial slice. The isocenter spacing is determined by adjacent collimator sizes. The weights are optimized by minimizing the deviation from ADCs using the steepest descentmore » technique. An iterative procedure is developed to reduce the number of isocenters, where the isocenter with lowest weight is removed without affecting plan quality. The ADC-DOF is compared with the genetic algorithm (GA) using the same arbitrary shaped target (254cc), with a 15mm margin ring structure representing normal tissues. Results: For ADC-DOF, the ADCs imposed on target and ring are (D100>10Gy, D50,10, 0<12Gy, 15Gy and 20Gy) and (D40<10Gy). The resulting D100, 50, 10, 0 and D40 are (9.9Gy, 12.0Gy, 14.1Gy and 16.2Gy) and (10.2Gy). The objectives of GA are to maximize 50% isodose target coverage (TC) while minimize the dose delivered to the ring structure, which results in 97% TC and 47.2% average dose in ring structure. For ADC-DOF (GA) techniques, 20 out of 38 (10 out of 12) initial isocenters are used in the final plan, and the computation time is 8.7s (412.2s) on an i5 computer. Conclusion: We have developed a new optimization technique using ADC and deterministic optimization. Compared with GA, ADC-DOF uses more isocenters but is faster and more robust, and achieves a better conformity. For future work, we will focus on developing a more effective mechanism for initial isocenter determination.« less

In-pixel conversion with a 10 bit SAR ADC for next generation X-ray FELs

NASA Astrophysics Data System (ADS)

Lodola, L.; Batignani, G.; Benkechkache, M. A.; Bettarini, S.; Casarosa, G.; Comotti, D.; Dalla Betta, G. F.; Fabris, L.; Forti, F.; Grassi, M.; Latreche, S.; Malcovati, P.; Manghisoni, M.; Mendicino, R.; Morsani, F.; Paladino, A.; Pancheri, L.; Paoloni, E.; Ratti, L.; Re, V.; Rizzo, G.; Traversi, G.; Vacchi, C.; Verzellesi, G.; Xu, H.

2016-07-01

This work presents the design of an interleaved Successive Approximation Register (SAR) ADC, part of the readout channel for the PixFEL detector. The PixFEL project aims at substantially advancing the state-of-the-art in the field of 2D X-ray imaging for applications at the next generation Free Electron Laser (FEL) facilities. For this purpose, the collaboration is developing the fundamental microelectronic building blocks for the readout channel. This work focuses on the design of the ADC carried out in a 65 nm CMOS technology. To obtain a good tradeoff between power consumption, conversion speed and area occupation, an interleaved SAR ADC architecture was adopted.

Changes of normal appearing optic nerve head on diffusion-weighted imaging in patients with diabetic retinopathy.

PubMed

Yılmaz, Sevda; Yumusak, Erhan; Burulday, Veysel

To investigate whether there is any change by measuring ADC values particularly of the optic nerve head (ONH) in patients with diabetic retinopathy (DR). ADC values at the ONHs was measured in 56 patients and 68 controls. ADC values of ONHs were significantly higher in patients with DR compared to controls (p=0.011). ADC values in patients with macular edema were higher than those without macular edema (p=0.017). DWI of ONHs can be useful in cases where it is difficult to assess macular edema during fundus examination, especially in diabetic patients with cataract. Copyright © 2016 Elsevier Inc. All rights reserved.

The diagnostic value of diffusion-weighted imaging and the apparent diffusion coefficient values in the differentiation of benign and malignant breast lesions.

PubMed

Çabuk, Gonca; Nass Duce, Meltem; Özgür, Anıl; Apaydın, Feramuz Demir; Polat, Ayşe; Orekici, Gülhan

2015-04-01

The goal of our study was to evaluate the diagnostic efficacy of diffusion-weighted imaging (DWI) in the differentiation of benign and malignant breast lesions. Between June 2012 and March 2013, 60 patients with 63 lesions (age range 29-70 years, mean age 48.6 years) were included in our study. All lesions, except complicated cysts and intra-mammary lymph nodes, were confirmed histopathologically. The patients were evaluated with a 1.5 Tesla MR scanner using dedicated bilateral breast coil. DWI images were obtained by echo planar imaging sequence and 'b' values were selected as 200, 600 and 1000 s/mm(2). Apparent diffusion coefficient (ADC) values of both breast lesions and the normal fibroglandular tissue of the contralateral breast were calculated and statistically compared using Shapiro-Wilk test, Student's t-test, Mann-Whitney U test, chi-square test and the receiver operating curve. Of 63 lesions, 22 were malignant and 41 were benign. In malignant lesions, the mean ADC values were 1.40 ± 0.41 × 10(-3) mm(2)/s for b = 200, 1.05 ± 0.28 × 10(-3) mm(2)/s for b = 600 and 0.91 ± 0.20 × 10(-3) mm(2)/s for b = 1000 and in benign lesions, the mean ADC values were 2.13 ± 0.85 × 10(-3) mm(2)/s for b = 200, 1.64 ± 0.47 × 10(-3) mm(2)/s for b = 600 and 1.40 ± 0.43 × 10(-3) mm(2)/s for b = 1000. The success of ADC values in differentiation of benign and malignant lesions was statistically significant (P = 0.0001). The threshold values were determined to be 1.50 × 10(-3) mm(2)/s for b = 200, 1.22 × 10(-3) mm(2)/s for b = 600 and 0.98 × 10(-3) mm(2)/s for b = 1000 (P < 0.05). DWI can be an effective radiological method in the differentiation of benign and malignant breast lesions. © 2015 The Royal Australian and New Zealand College of Radiologists.

Testing of the Engineering Model Electrical Power Control Unit for the Fluids and Combustion Facility

NASA Technical Reports Server (NTRS)

Kimnach, Greg L.; Lebron, Ramon C.; Fox, David A.

1999-01-01

The John H. Glenn Research Center at Lewis Field (GRC) in Cleveland, OH and the Sundstrand Corporation in Rockford, IL have designed and developed an Engineering Model (EM) Electrical Power Control Unit (EPCU) for the Fluids Combustion Facility, (FCF) experiments to be flown on the International Space Station (ISS). The EPCU will be used as the power interface to the ISS power distribution system for the FCF's space experiments'test and telemetry hardware. Furthermore. it is proposed to be the common power interface for all experiments. The EPCU is a three kilowatt 12OVdc-to-28Vdc converter utilizing three independent Power Converter Units (PCUs), each rated at 1kWe (36Adc @ 28Vdc) which are paralleled and synchronized. Each converter may be fed from one of two ISS power channels. The 28Vdc loads are connected to the EPCU output via 48 solid-state and current-limiting switches, rated at 4Adc each. These switches may be paralleled to supply any given load up to the 108Adc normal operational limit of the paralleled converters. The EPCU was designed in this manner to maximize allocated-power utilization. to shed loads autonomously, to provide fault tolerance. and to provide a flexible power converter and control module to meet various ISS load demands. Tests of the EPCU in the Power Systems Facility testbed at GRC reveal that the overall converted-power efficiency, is approximately 89% with a nominal-input voltage of 12OVdc and a total load in the range of 4O% to 110% rated 28Vdc load. (The PCUs alone have an efficiency of approximately 94.5%). Furthermore, the EM unit passed all flight-qualification level (and beyond) vibration tests, passed ISS EMI (conducted, radiated. and susceptibility) requirements. successfully operated for extended periods in a thermal/vacuum chamber, was integrated with a proto-flight experiment and passed all stability and functional requirements.

Preparation of astaxanthin-loaded DNA/chitosan nanoparticles for improved cellular uptake and antioxidation capability.

PubMed

Wang, Qian; Zhao, Yingyuan; Guan, Lei; Zhang, Yaping; Dang, Qifeng; Dong, Ping; Li, Jing; Liang, Xingguo

2017-07-15

DNA/chitosan co-assemblies were initially used as nanocarriers for efficient astaxanthin encapsulation and delivery. The obtained astaxanthin-loaded DNA/chitosan (ADC) colloidal system was transparent and homogenous, with astaxanthin content up to 65μg/ml. Compared to free astaxanthin, ADC nanoparticles with an astaxanthin concentration as low as 3.35nM still showed a more powerful cytoprotective effect on H 2 O 2 -induced oxidative cell damage, and improved cell viability from 49.9% to 61.9%. The ROS scavenging efficiency of ADC nanoparticles was as high as 54.3%, which was 2-fold higher than that of free astaxanthin. Besides this, ADC nanoparticles were easily engulfed by Caco-2 cells in a short time, indicating that the encapsulated astaxanthin could be absorbed through endocytosis by intestinal epithelial cells. The improved antioxidation capability and facilitated cellular uptake enabled the ADC nanoparticles to be good candidates for efficient delivery and absorption of astaxanthin. Copyright © 2017 Elsevier Ltd. All rights reserved.

Joint groupwise registration and ADC estimation in the liver using a B-value weighted metric.

PubMed

Sanz-Estébanez, Santiago; Rabanillo-Viloria, Iñaki; Royuela-Del-Val, Javier; Aja-Fernández, Santiago; Alberola-López, Carlos

2018-02-01

The purpose of this work is to develop a groupwise elastic multimodal registration algorithm for robust ADC estimation in the liver on multiple breath hold diffusion weighted images. We introduce a joint formulation to simultaneously solve both the registration and the estimation problems. In order to avoid non-reliable transformations and undesirable noise amplification, we have included appropriate smoothness constraints for both problems. Our metric incorporates the ADC estimation residuals, which are inversely weighted according to the signal content in each diffusion weighted image. Results show that the joint formulation provides a statistically significant improvement in the accuracy of the ADC estimates. Reproducibility has also been measured on real data in terms of the distribution of ADC differences obtained from different b-values subsets. The proposed algorithm is able to effectively deal with both the presence of motion and the geometric distortions, increasing accuracy and reproducibility in diffusion parameters estimation. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Novel antibody drug conjugates containing exatecan derivative-based cytotoxic payloads.

PubMed

Nakada, Takashi; Masuda, Takeshi; Naito, Hiroyuki; Yoshida, Masao; Ashida, Shinji; Morita, Koji; Miyazaki, Hideki; Kasuya, Yuji; Ogitani, Yusuke; Yamaguchi, Junko; Abe, Yuki; Honda, Takeshi

2016-03-15

Trastuzumab conjugates consisting of exatecan derivatives were prepared and their biological activities and physicochemical properties were evaluated. The ADCs showed strong efficacy and a low aggregation rate. The exatecan derivatives were covalently connected via a peptidyl spacer (Gly-Gly-Phe-Gly), which is assumed to be stable in circulation, and were cleaved by lysosomal enzymes following ADC internalization into tumor tissue. These anti-HER2 ADCs exhibited a high potency, specifically against HER2-positive cancer cell lines in vitro. The ADCs, bearing exatecan derivatives which have more than two methylene chains, exhibited superior cytotoxicity. It was speculated that steric hindrance of the cleavable amide moiety could be involved in the drug release. The adequate alkyl lengths of exatecan derivatives (13, 14, 15) were from two to four in terms of aggregation rate. The ADC having a hydrophilic moiety showed good efficacy in a HER2-positive and Trastuzumab-resistant breast carcinoma cell model in mice. Copyright © 2016 Elsevier Ltd. All rights reserved.

Effect of inhibitors of polyamine biosynthesis on gibberellin-induced internode growth in light-grown dwarf peas

NASA Technical Reports Server (NTRS)

Kaur-Sawhney, R.; Dai, Y. R.; Galston, A. W.

1986-01-01

When gibberellic acid (GA3) is sprayed on 9-day-old light-brown dwarf Progress pea (Pisum sativum) seedlings, arginine decarboxylase (ADC; EC 4.1.1.9) activity increases within 3 h and peaks at about 9 h after GA3 application. This is followed by a second lower peak at about 30 h; both peaks were higher than the corresponding peaks in the controls. In contrast, no appreciable effect of GA3 on internode length was observed until about 12 h, after which time a dramatic increase in growth rate occurred and persisted for about 12 h. Specific (DL-alpha-difluoromethylarginine) and non-specific (D-arginine and L-canavanine) inhibitors of ADC strongly inhibited ADC activity and to a lesser extent internode growth. The inhibition was reversed only slightly by the addition of polyamines. Actinomycin D and cycloheximide inhibited the rise in ADC activity induced by GA3. The half-life of the enzyme was increased by GA3 treatment. The results suggest that part of the GA3-induced increase in internode growth may result from enhanced polyamine biosynthesis through the ADC pathway. Furthermore, the GA3 induced increase in ADC activity probably requires de novo synthesis of both RNA and protein.

Antibody-drug conjugates: Promising and efficient tools for targeted cancer therapy.

PubMed

Nasiri, Hadi; Valedkarimi, Zahra; Aghebati-Maleki, Leili; Majidi, Jafar

2018-09-01

Over the recent decades, the use of antibody-drug conjugates (ADCs) has led to a paradigm shift in cancer chemotherapy. Antibody-based treatment of various human tumors has presented dramatic efficacy and is now one of the most promising strategies used for targeted therapy of patients with a variety of malignancies, including hematological cancers and solid tumors. Monoclonal antibodies (mAbs) are able to selectively deliver cytotoxic drugs to tumor cells, which express specific antigens on their surface, and has been suggested as a novel category of agents for use in the development of anticancer targeted therapies. In contrast to conventional treatments that cause damage to healthy tissues, ADCs use mAbs to specifically attach to antigens on the surface of target cells and deliver their cytotoxic payloads. The therapeutic success of future ADCs depends on closely choosing the target antigen, increasing the potency of the cytotoxic cargo, improving the properties of the linker, and reducing drug resistance. If appropriate solutions are presented to address these issues, ADCs will play a more important role in the development of targeted therapeutics against cancer in the next years. We review the design of ADCs, and focus on how ADCs can be exploited to overcome multiple drug resistance (MDR). © 2018 Wiley Periodicals, Inc.