Design and Analysis of an Attitude Determination and Control Subsystem (ADCS) for AFIT’s 6U Standard Bus

DTIC Science & Technology

2014-03-27

Fault Detection and Isolation GUI Graphical User Interface IGRF International Geomagnetic Reference Field IMU Inertial Measurement Unit IR infrared xv...ADCS hardware components were either commercially purchased or built in-house and include an Inertial Measurement Unit ( IMU ), external magnetometer, 4...3.2.1.3 IMU . . . . . . . . . . . . . . . . . . . . . . . . . . . . 46 3.2.1.4 External Magnetometer . . . . . . . . . . . . . . . . . . 48 3.2.2

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.

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.

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

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

FDG-PET/CT and diffusion-weighted imaging for resected lung cancer: correlation of maximum standardized uptake value and apparent diffusion coefficient value with prognostic factors.

PubMed

Usuda, Katsuo; Funasaki, Aika; Sekimura, Atsushi; Motono, Nozomu; Matoba, Munetaka; Doai, Mariko; Yamada, Sohsuke; Ueda, Yoshimichi; Uramoto, Hidetaka

2018-04-09

Diffusion-weighted magnetic resonance imaging (DWI) is useful for detecting malignant tumors and the assessment of lymph nodes, as FDG-PET/CT is. But it is not clear how DWI influences the prognosis of lung cancer patients. The focus of this study is to evaluate the correlations between maximum standardized uptake value (SUVmax) of FDG-PET/CT and apparent diffusion coefficient (ADC) value of DWI with known prognostic factors in resected lung cancer. A total of 227 patients with resected lung cancers were enrolled in this study. FEG-PET/CT and DWI were performed in each patient before surgery. There were 168 patients with adenocarcinoma, 44 patients with squamous cell carcinoma, and 15 patients with other cell types. SUVmax was a factor that was correlated to T factor, N factor, or cell differentiation. ADC of lung cancer was a factor that was not correlated to T factor, or N factor. There was a significantly weak inverse relationship between SUVmax and ADC (Correlation coefficient r = - 0.227). In analysis of survival, there were significant differences between the categories of sex, age, pT factor, pN factor, cell differentiation, cell type, and SUVmax. Univariate analysis revealed that SUVmax, pN factor, age, cell differentiation, cell type, sex, and pT factor were significant factors. Multivariate analysis revealed that SUVmax and pN factor were independent significant prognostic factors. SUVmax was a significant prognostic factor that is correlated to T factor, N factor, or cell differentiation, but ADC was not. SUVmax may be more useful for predicting the prognosis of lung cancer than ADC values.

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.

Quantitative evaluation of diffusion-kurtosis imaging for grading endometrial carcinoma: a comparative study with diffusion-weighted imaging.

PubMed

Chen, T; Li, Y; Lu, S-S; Zhang, Y-D; Wang, X-N; Luo, C-Y; Shi, H-B

2017-11-01

To evaluate the diagnostic performance of histogram analysis of diffusion kurtosis magnetic resonance imaging (DKI) and standard diffusion-weighted imaging (DWI) in discriminating tumour grades of endometrial carcinoma (EC). Seventy-three patients with EC were included in this study. The apparent diffusion coefficient (ADC) value from standard DWI, apparent diffusion for Gaussian distribution (D app ), and apparent kurtosis coefficient (K app ) from DKI were acquired using a 3 T magnetic resonance imaging (MRI) system. The measurement was based on an entire-tumour analysis. Histogram parameters (D app , K app , and ADC) were compared between high-grade (grade 3) and low-grade (grade 1 and 2) tumours. The diagnostic performance of imaging parameters for discriminating high- from low-grade tumours was analysed using a receiver operating characteristic curve (ROC). The area under the ROC curve (AUC) of the 10th percentile of D app , 90th percentile of K app and 10th percentile of ADC were higher than other parameters in distinguishing high-grade tumours from low-grade tumours (AUC=0.821, 0.891 and 0.801, respectively). The combination of 10th percentile of D app and 90th percentile of K app improved the AUC to 0.901, which was significantly higher than that of the 10th percentile of ADC (0.810, p=0.0314) in differentiating high- from low-grade EC. Entire-tumour volume histogram analysis of DKI and standard DWI were feasible for discriminating histological tumour grades of EC. DKI was relatively better than DWI in distinguishing high-grade from low-grade tumour in EC. Copyright © 2017. Published by Elsevier Ltd.

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 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.

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.

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.

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

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.

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.

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.

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.

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

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.

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.

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

Diffusion-weighted imaging of the breast: principles and clinical applications.

PubMed

Woodhams, Reiko; Ramadan, Saadallah; Stanwell, Peter; Sakamoto, Satoko; Hata, Hirofumi; Ozaki, Masanori; Kan, Shinichi; Inoue, Yusuke

2011-01-01

Diffusion-weighted imaging provides a novel contrast mechanism in magnetic resonance (MR) imaging and has a high sensitivity in the detection of changes in the local biologic environment. A significant advantage of diffusion-weighted MR imaging over conventional contrast material-enhanced MR imaging is its high sensitivity to change in the microscopic cellular environment without the need for intravenous contrast material injection. Approaches to the assessment of diffusion-weighted breast imaging findings include assessment of these data alone and interpretation of the data in conjunction with T2-weighted imaging findings. In addition, the analysis of apparent diffusion coefficient (ADC) value can be undertaken either in isolation or in combination with diffusion-weighted and T2-weighted imaging. Most previous studies have evaluated ADC value alone; however, overlap in the ADC values of malignant and benign disease has been observed. This overlap may be partly due to selection of b value, which can influence the concomitant effect of perfusion and emphasize the contribution of multicomponent model influences. The simultaneous assessment of diffusion-weighted and T2-weighted imaging data and ADC value has the potential to improve specificity. In addition, the use of diffusion-weighted imaging in a standard breast MR imaging protocol may heighten sensitivity and thereby improve diagnostic accuracy. Standardization of diffusion-weighted imaging parameters is needed to allow comparison of multicenter studies and assessment of the clinical utility of diffusion-weighted imaging and ADC values in breast evaluation.

76 FR 16588 - Combined Mailings of Standard Mail and Periodicals Flats

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-24

... may be combined in carrier route, 5-digit (scheme), 3-digit, ADC, and Mixed ADC bundles when prepared...-digit scheme through NDC pallets must contain at least 250 pounds of combined Standard Mail and... scheme through NDC pallets must contain at least 250 pounds of combined Standard Mail and Periodicals...

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.

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.

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.

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.

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Federal Register 2010, 2011, 2012, 2013, 2014

2011-02-28

... (scheme), 3-digit, ADC, and Mixed ADC bundles when prepared according to 707.19.0 and these additional... to the standards in 8.0 and in the sequence listed below. Merged 5-digit scheme through NDC pallets... according to the standards in 8.0 and in the sequence listed below. Merged 5-digit scheme through NDC...

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.

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.

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.

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 histogram analysis can evaluate radiation-induced parotid damage and predict late xerostomia degree in nasopharyngeal carcinoma

PubMed Central

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

2017-01-01

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, 75th and 90th percentiles continued to increase (P = 0.024, 0.010, and 0.006, respectively). Early change rates of parotid ADCmean, ADCmin, kurtosis, and 25th, 50th, 75th, 90th 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 ADCmax 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. PMID:29050274

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.

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.

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.

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.

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.

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.

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, M.; Grunberg, M.; Engels, F.

2015-03-01

In order to improve an existing network, a field seismologist would have to add some extra sensors to a remote station. However, additional ADCs (analogue-to-digital converters) are not always implemented on commercial dataloggers, or, if they are, they may already be used. Installing additional ADCs often implies an expensive development, or the purchase of a new datalogger. We present here a simple method to take advantage of the ADCs of an embedded computer in order to create data in a seismological standard format and integrate them within the real-time data stream from the station. Our first goal is to plug temperature and pressure sensors on the ADCs, read data and record them in mini-seed format (seed stands for Standard for the Exchange of the Earthquake Data), and eventually transfer them to a central server together with the seismic data, by using seedlink, since mini-seed and seedlink are standard for seismology.

Adjustable Nyquist-rate System for Single-Bit Sigma-Delta ADC with Alternative FIR Architecture

NASA Astrophysics Data System (ADS)

Frick, Vincent; Dadouche, Foudil; Berviller, Hervé

2016-09-01

This paper presents a new smart and compact system dedicated to control the output sampling frequency of an analogue-to-digital converters (ADC) based on single-bit sigma-delta (ΣΔ) modulator. This system dramatically improves the spectral analysis capabilities of power network analysers (power meters) by adjusting the ADC's sampling frequency to the input signal's fundamental frequency with a few parts per million accuracy. The trade-off between straightforwardness and performance that motivated the choice of the ADC's architecture are preliminary discussed. It particularly comes along with design considerations of an ultra-steep direct-form FIR that is optimised in terms of size and operating speed. Thanks to compact standard VHDL language description, the architecture of the proposed system is particularly suitable for application-specific integrated circuit (ASIC) implementation-oriented low-power and low-cost power meter applications. Field programmable gate array (FPGA) prototyping and experimental results validate the adjustable sampling frequency concept. They also show that the system can perform better in terms of implementation and power capabilities compared to dedicated IP resources.

Task-based evaluation of segmentation algorithms for diffusion-weighted MRI without using a gold standard

PubMed Central

Jha, Abhinav K.; Kupinski, Matthew A.; Rodríguez, Jeffrey J.; Stephen, Renu M.; Stopeck, Alison T.

2012-01-01

In many studies, the estimation of the apparent diffusion coefficient (ADC) of lesions in visceral organs in diffusion-weighted (DW) magnetic resonance images requires an accurate lesion-segmentation algorithm. To evaluate these lesion-segmentation algorithms, region-overlap measures are used currently. However, the end task from the DW images is accurate ADC estimation, and the region-overlap measures do not evaluate the segmentation algorithms on this task. Moreover, these measures rely on the existence of gold-standard segmentation of the lesion, which is typically unavailable. In this paper, we study the problem of task-based evaluation of segmentation algorithms in DW imaging in the absence of a gold standard. We first show that using manual segmentations instead of gold-standard segmentations for this task-based evaluation is unreliable. We then propose a method to compare the segmentation algorithms that does not require gold-standard or manual segmentation results. The no-gold-standard method estimates the bias and the variance of the error between the true ADC values and the ADC values estimated using the automated segmentation algorithm. The method can be used to rank the segmentation algorithms on the basis of both accuracy and precision. We also propose consistency checks for this evaluation technique. PMID:22713231

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.

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.

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.

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.

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.

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.

Comparing clinical profiles in Alzheimer's disease and Parkinson's disease dementia.

PubMed

Farlow, Martin R; Schmitt, Frederick; Aarsland, Dag; Grossberg, George T; Somogyi, Monique; Meng, Xiangyi

2013-01-01

Greater understanding of differences in baseline impairment and disease progression in patients with Alzheimer's disease (AD) and Parkinson's disease dementia (PDD) may improve the interpretation of drug effects and the design of future studies. This was a retrospective analysis of three randomized, double-blind rivastigmine databases (one in PDD, two in AD). Impairment on the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog), Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) scale, 10-item Neuropsychiatric Inventory (NPI-10) and the ADCS-Clinical Global Impression of Change (CGIC) was compared [standardized difference (Cohen's d), similar if <0.1]. Patients with AD or PDD had similar levels of impairment on the ADAS-cog and NPI-10. Scores on the ADCS-ADL scale (standardized difference = 0.47) and the ADAS-cog memory domain (total, 0.33; items, 0.10-0.58) were higher in AD; PDD patients were more impaired in the language (0.23) and praxis (0.34) domains. AD patients receiving placebo showed greater deterioration on the ADAS-cog (0.14) and improvement on the NPI-10 (0.11) compared with patients with PDD. Differing patterns of impairment occur in AD and PDD.

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

Comparison of Absolute Apparent Diffusion Coefficient (ADC) Values in ADC Maps Generated Across Different Postprocessing Software: Reproducibility in Endometrial Carcinoma.

PubMed

Ghosh, Adarsh; Singh, Tulika; Singla, Veenu; Bagga, Rashmi; Khandelwal, Niranjan

2017-12-01

Apparent diffusion coefficient (ADC) maps are usually generated by builtin software provided by the MRI scanner vendors; however, various open-source postprocessing software packages are available for image manipulation and parametric map generation. The purpose of this study is to establish the reproducibility of absolute ADC values obtained using different postprocessing software programs. DW images with three b values were obtained with a 1.5-T MRI scanner, and the trace images were obtained. ADC maps were automatically generated by the in-line software provided by the vendor during image generation and were also separately generated on postprocessing software. These ADC maps were compared on the basis of ROIs using paired t test, Bland-Altman plot, mountain plot, and Passing-Bablok regression plot. There was a statistically significant difference in the mean ADC values obtained from the different postprocessing software programs when the same baseline trace DW images were used for the ADC map generation. For using ADC values as a quantitative cutoff for histologic characterization of tissues, standardization of the postprocessing algorithm is essential across processing software packages, especially in view of the implementation of vendor-neutral archiving.

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.

Apparent diffusion coefficient histogram metrics correlate with survival in diffuse intrinsic pontine glioma: a report from the Pediatric Brain Tumor Consortium

PubMed Central

Poussaint, Tina Young; Vajapeyam, Sridhar; Ricci, Kelsey I.; Panigrahy, Ashok; Kocak, Mehmet; Kun, Larry E.; Boyett, James M.; Pollack, Ian F.; Fouladi, Maryam

2016-01-01

Background Diffuse intrinsic pontine glioma (DIPG) is associated with poor survival regardless of therapy. We used volumetric apparent diffusion coefficient (ADC) histogram metrics to determine associations with progression-free survival (PFS) and overall survival (OS) at baseline and after radiation therapy (RT). Methods Baseline and post-RT quantitative ADC histograms were generated from fluid-attenuated inversion recovery (FLAIR) images and enhancement regions of interest. Metrics assessed included number of peaks (ie, unimodal or bimodal), mean and median ADC, standard deviation, mode, skewness, and kurtosis. Results Based on FLAIR images, the majority of tumors had unimodal peaks with significantly shorter average survival. Pre-RT FLAIR mean, mode, and median values were significantly associated with decreased risk of progression; higher pre-RT ADC values had longer PFS on average. Pre-RT FLAIR skewness and standard deviation were significantly associated with increased risk of progression; higher pre-RT FLAIR skewness and standard deviation had shorter PFS. Nonenhancing tumors at baseline showed higher ADC FLAIR mean values, lower kurtosis, and higher PFS. For enhancing tumors at baseline, bimodal enhancement histograms had much worse PFS and OS than unimodal cases and significantly lower mean peak values. Enhancement in tumors only after RT led to significantly shorter PFS and OS than in patients with baseline or no baseline enhancement. Conclusions ADC histogram metrics in DIPG demonstrate significant correlations between diffusion metrics and survival, with lower diffusion values (increased cellularity), increased skewness, and enhancement associated with shorter survival, requiring future investigations in large DIPG clinical trials. PMID:26487690

MO-F-CAMPUS-I-05: Quantitative ADC Measurement of Esophageal Cancer Before and After Chemoradiation

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

Yang, L; UT MD Anderson Cancer Center, Houston, TX; Son, JB

2015-06-15

Purpose: We investigated whether quantitative diffusion imaging can be used as an imaging biomarker for early prediction of treatment response of esophageal cancer. Methods: Eight patients with esophageal cancer underwent a baseline and an interim MRI studies during chemoradiation on a 3T whole body MRI scanner with an 8-channel torso phased array coil. Each MRI study contained two axial diffusion-weighted imaging (DWI) series with a conventional DWI sequence and a reduced field-of-view DWI sequence (FOCUS) of varying b-values. ADC maps with two b-values were computed from conventional DWI images using a mono-exponential model. For each of DWI sequences, separate ADCallmore » was computed by fitting the signal intensity of images with all the b-values to a single exponential model. For the FOCUS sequence, a bi-exponential model was used to extract perfusion and diffusion coefficients (ADCperf and ADCdiff) and their contributions to the signal decay. A board-certified radiologist contoured the tumor region and mean ADC values and standard deviations of tumor and muscle ROIs were recorded from different ADC maps. Results: Our results showed that (1) the magnitude of ADCs from the same ROIs by the different analysis methods can be substantially different. (2) For a given method, the change between the baseline and interim muscle ADCs was relatively small (≤10%). In contrast, the change between the baseline and interim tumor ADCs was substantially larger, with the change in ADCdiff by FOCUS DWI showing the largest percentage change of 73.2%. (3) The range of the relative change of a specific parameter for different patients was also different. Conclusion: Presently, we do not have the final pathological confirmation of the treatment response for all the patients. However, for a few patients whose surgical specimen is available, the quantitative ADC changes have been found to be useful as a potential predictor for treatment response.« less

The flexibility of a generic LC-MS/MS method for the quantitative analysis of therapeutic proteins based on human immunoglobulin G and related constructs in animal studies.

PubMed

Lanshoeft, Christian; Wolf, Thierry; Walles, Markus; Barteau, Samuel; Picard, Franck; Kretz, Olivier; Cianférani, Sarah; Heudi, Olivier

2016-11-30

An increasing demand of new analytical methods is associated with the growing number of biotherapeutic programs being prosecuted in the pharmaceutical industry. Whilst immunoassay has been the standard method for decades, a great interest in assays based on liquid chromatography tandem mass spectrometry (LC-MS/MS) is evolving. In this present work, the development of a generic method for the quantitative analysis of therapeutic proteins based on human immunoglobulin G (hIgG) in rat serum is reported. The method is based on four generic peptides GPSVFPLAPSSK (GPS), TTPPVLDSDGSFFLYSK (TTP), VVSVLTVLHQDWLNGK (VVS) and FNWYVDGVEVHNAK (FNW) originating from different parts of the fraction crystallizable (Fc) region of a reference hIgG1 (hIgG1A). A tryptic pellet digestion of rat serum spiked with hIgG1A and a stable isotope labeled protein (hIgG1B) used as internal standard (ISTD) was applied prior LC-MS/MS analysis. The upper limit of quantification was at 1000μg/mL. The lower limit of quantitation was for GPS, TTP and VVS at 1.00μg/mL whereas for FNW at 5.00μg/mL. Accuracy and precision data met acceptance over three days. The presented method was further successfully applied to the quantitative analysis of other hIgG1s (hIgG1C and hIgG1D) and hIgG4-based therapeutic proteins on spiked quality control (QC) samples in monkey and rat serum using calibration standards (Cs) prepared with hIgG1A in rat serum. In order to extend the applicability of our generic approach, a bispecific-bivalent hIgG1 (bb-hIgG1) and two lysine conjugated antibody-drug conjugates (ADC1 and ADC2) were incorporated as well. The observed values on spiked QC samples in monkey serum were satisfactory with GPS for the determination of bb-hIgG1 whereas the FNW and TTP peptides were suitable for the ADCs. Moreover, comparable mean concentration-time profiles were obtained from monkeys previously dosed intravenously with ADC2 measured against Cs samples prepared either with hIgG1A in rat serum (presented approach) or with the actual ADC2 in monkey serum (conventional approach). The results of this study highlight the great flexibility of our newly developed generic approach and that the choice of the surrogate peptide still remains critical when dealing with different matrix types or modalities. Copyright © 2016 Elsevier B.V. All rights reserved.

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.

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.

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.

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.

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.

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%.

Rectal cancer: assessment of complete response to preoperative combined radiation therapy with chemotherapy--conventional MR volumetry versus diffusion-weighted MR imaging.

PubMed

Curvo-Semedo, Luís; Lambregts, Doenja M J; Maas, Monique; Thywissen, Thomas; Mehsen, Rana T; Lammering, Guido; Beets, Geerard L; Caseiro-Alves, Filipe; Beets-Tan, Regina G H

2011-09-01

To determine diagnostic performance of diffusion-weighted (DW) magnetic resonance (MR) imaging for assessment of complete tumor response (CR) after combined radiation therapy with chemotherapy (CRT) in patients with locally advanced rectal cancer (LARC) by means of volumetric signal intensity measurements and apparent diffusion coefficient (ADC) measurements and to compare the performance of DW imaging with that of T2-weighted MR volumetry. A retrospective analysis of 50 patients with LARC, for whom clinical and imaging data were retrieved from a previous imaging study approved by the local institutional ethical committee and for which all patients provided informed consent, was conducted. Patients underwent pre- and post-CRT standard T2-weighted MR and DW MR. Two independent readers placed free-hand regions of interest (ROIs) in each tumor-containing section on both data sets to determine pre- and post-CRT tumor volumes and tumor volume reduction rates (volume). ROIs were copied to an ADC map to calculate tumor ADCs. Histopathologic findings were the standard of reference. Receiver operating characteristic (ROC) curves were generated to compare performance of T2-weighted and DW MR volumetry and ADC. The intraclass correlation coefficient (ICC) was used to evaluate interobserver variability and the correlation between T2-weighted and DW MR volumetry. Areas under the ROC curve (AUCs) for identification of a CR that was based on pre-CRT volume, post-CRT volume, and volume, respectively, were 0.57, 0.70, and 0.84 for T2-weighted MR versus 0.63, 0.93, and 0.92 for DW MR volumetry (P = .15, .02, .42). Pre- and post-CRT ADC and ADC AUCs were 0.55, 0.54, and 0.51, respectively. Interobserver agreement was excellent for all pre-CRT measurements (ICC, 0.91-0.96) versus good (ICC, 0.61-0.79) for post-CRT measurements. ICC between T2-weighted and DW MR volumetry was excellent (0.97) for pre-CRT measurements versus fair (0.25) for post-CRT measurements. Post-CRT DW MR volumetry provided high diagnostic performance in assessing CR and was significantly more accurate than T2-weighted MR volumetry. Post-CRT DW MR was equally as accurate as volume measurements of both T2-weighted and DW MR. Pre-CRT volumetry and ADC were not reliable.

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.

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.

Application of XML to Journal Table Archiving

NASA Astrophysics Data System (ADS)

Shaya, E. J.; Blackwell, J. H.; Gass, J. E.; Kargatis, V. E.; Schneider, G. L.; Weiland, J. L.; Borne, K. D.; White, R. A.; Cheung, C. Y.

1998-12-01

The Astronomical Data Center (ADC) at the NASA Goddard Space Flight Center is a major archive for machine-readable astronomical data tables. Many ADC tables are derived from published journal articles. Article tables are reformatted to be machine-readable and documentation is crafted to facilitate proper reuse by researchers. The recent switch of journals to web based electronic format has resulted in the generation of large amounts of tabular data that could be captured into machine-readable archive format at fairly low cost. The large data flow of the tables from all major North American astronomical journals (a factor of 100 greater than the present rate at the ADC) necessitates the development of rigorous standards for the exchange of data between researchers, publishers, and the archives. We have selected a suitable markup language that can fully describe the large variety of astronomical information contained in ADC tables. The eXtensible Markup Language XML is a powerful internet-ready documentation format for data. It provides a precise and clear data description language that is both machine- and human-readable. It is rapidly becoming the standard format for business and information transactions on the internet and it is an ideal common metadata exchange format. By labelling, or "marking up", all elements of the information content, documents are created that computers can easily parse. An XML archive can easily and automatically be maintained, ingested into standard databases or custom software, and even totally restructured whenever necessary. Structuring astronomical data into XML format will enable efficient and focused search capabilities via off-the-shelf software. The ADC is investigating XML's expanded hyperlinking power to enhance connectivity within the ADC data/metadata and developing XSL display scripts to enhance display of astronomical data. The ADC XML Definition Type Document can be viewed at http://messier.gsfc.nasa.gov/dtdhtml/DTD-TREE.html

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

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

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

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.

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.

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.

Diffusion kurtosis imaging of the liver at 3 Tesla: in vivo comparison to standard diffusion-weighted imaging.

PubMed

Budjan, Johannes; Sauter, Elke A; Zoellner, Frank G; Lemke, Andreas; Wambsganss, Jens; Schoenberg, Stefan O; Attenberger, Ulrike I

2018-01-01

Background Functional techniques like diffusion-weighted imaging (DWI) are gaining more and more importance in liver magnetic resonance imaging (MRI). Diffusion kurtosis imaging (DKI) is an advanced technique that might help to overcome current limitations of DWI. Purpose To evaluate DKI for the differentiation of hepatic lesions in comparison to conventional DWI at 3 Tesla. Material and Methods Fifty-six consecutive patients were examined using a routine abdominal MR protocol at 3 Tesla which included DWI with b-values of 50, 400, 800, and 1000 s/mm 2 . Apparent diffusion coefficient maps were calculated applying a standard mono-exponential fit, while a non-Gaussian kurtosis fit was used to obtain DKI maps. ADC as well as Kurtosis-corrected diffusion ( D) values were quantified by region of interest analysis and compared between lesions. Results Sixty-eight hepatic lesions (hepatocellular carcinoma [HCC] [n = 25]; hepatic adenoma [n = 4], cysts [n = 18]; hepatic hemangioma [HH] [n = 18]; and focal nodular hyperplasia [n = 3]) were identified. Differentiation of malignant and benign lesions was possible based on both DWI ADC as well as DKI D-values ( P values were in the range of 0.04 to < 0.0001). Conclusion In vivo abdominal DKI calculated using standard b-values is feasible and enables quantitative differentiation between malignant and benign liver lesions. Assessment of conventional ADC values leads to similar results when using b-values below 1000 s/mm 2 for DKI calculation.

77 FR 38759 - New Pallet Preparation Standards for Periodicals

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-29

... similar containers. DATES: Submit comments on or before July 30, 2012. ADDRESSES: Mail or deliver written... area distribution center (ADC) sacks (or similar containers), labeled according to labeling list L009; and in origin mixed ADC (OMX) sacks (or similar containers), labeled according to labeling list L201...

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.

Prognostic value of diffusion-weighted imaging summation scores or apparent diffusion coefficient maps in newborns with hypoxic-ischemic encephalopathy.

PubMed

Cavalleri, Francesca; Lugli, Licia; Pugliese, Marisa; D'Amico, Roberto; Todeschini, Alessandra; Della Casa, Elisa; Gallo, Claudio; Frassoldati, Rossella; Ferrari, Fabrizio

2014-09-01

The diagnostic and prognostic assessment of newborn infants with hypoxic-ischemic encephalopathy (HIE) comprises, among other tools, diffusion-weighted imaging (DWI) and apparent diffusion coefficient (ADC) maps. To compare the ability of DWI and ADC maps in newborns with HIE to predict the neurodevelopmental outcome at 2 years of age. Thirty-four term newborns with HIE admitted to the Neonatal Intensive Care Unit of Modena University Hospital from 2004 to 2008 were consecutively enrolled in the study. All newborns received EEG, conventional MRI and DWI within the first week of life. DWI was analyzed by means of summation (S) score and regional ADC measurements. Neurodevelopmental outcome was assessed with a standard 1-4 scale and the Griffiths Mental Developmental Scales - Revised (GMDS-R). When the outcome was evaluated with a standard 1-4 scale, the DWI S scores showed very high area under the curve (AUC) (0.89) whereas regional ADC measurements in specific subregions had relatively modest predictive value. The lentiform nucleus was the region with the highest AUC (0.78). When GMDS-R were considered, DWI S scores were good to excellent predictors for some GMDS-R subscales. The predictive value of ADC measurements was both region- and subscale-specific. In particular, ADC measurements in some regions (basal ganglia, white matter or rolandic cortex) were excellent predictors for specific GMDS-R with AUCs up to 0.93. DWI S scores showed the highest prognostic value for the neurological outcome at 2 years of age. Regional ADC measurements in specific subregions proved to be highly prognostic for specific neurodevelopmental outcomes.

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.

Histogram analysis of stretched-exponential and monoexponential diffusion-weighted imaging models for distinguishing low and intermediate/high gleason scores in prostate carcinoma.

PubMed

Liu, Wei; Liu, Xiao H; Tang, Wei; Gao, Hong B; Zhou, Bing N; Zhou, Liang P

2018-02-07

Noninvasive measures to evaluate the aggressiveness of prostate carcinoma (PCa) may benefit patients. To assess the value of stretched-exponential and monoexponential diffusion-weighted imaging (DWI) for predicting the aggressiveness of PCa. Retrospective study. Seventy-five patients with PCa. 3T DWI examinations were performed using b-values of 0, 500, 1000, and 2000 s/mm 2 . The research were based on entire-tumor histogram analysis and the reference standard was radical prostectomy. The correlation analysis was programmed with Spearman's rank-order analysis between the histogram variables and Gleason grade group (GG). Receiver operating characteristic (ROC) regression was used to analyze the ability of these histogram variables to differentiate low-grade (LG) from intermediate/high-grade (HG) PCa. The percentiles and mean of apparent diffusion coefficient (ADC) and distributed diffusion coefficient (DDC) were correlated with GG (ρ: 0.414-0.593), while there was no significant relation among α value, skewnesses, and kurtosises with GG (ρ:0.034-0.323). HG tumors (ADC:484 ± 136, 592 ± 139, 670 ± 144, 788 ± 146, 895 ± 141 mm 2 /s; DDC: 410 ± 142, 532 ± 172, 666 ± 193, 786 ± 196, 914 ± 181 mm 2 /s) had lower values in the 10 th , 25 th , 50 th , 75 th percentiles and means than LG tumors (ADC: 644 ± 779, 737 ± 84, 836 ± 83, 919 ± 82, 997 ± 107 mm 2 /s; DDC: 552 ± 82, 680 ± 94, 829 ± 112, 931 ± 106, 1045 ± 100 mm 2 /s). However, there was no difference between LG and HG tumors in α value (0.671 ± 0.041 vs. 0.633 ± 0.114), kurtosises (ADC 0.09 vs. 0.086; DDC -0.033 vs. -0.317), or skewnesses (ADC -0.036 vs. 0.073; DDC -0.063 vs. 0.136). The above statistics were P < 0.01. ADC10 with AUC = 0.840 and DDC10 with AUC = 0.799 were similar in discriminating between LG and HG PCa at P < 0.05. Histogram variables of DDC and ADC may predict the aggressiveness of PCa, while α value does not. The abilities of ADC10 and DDC10 to discriminate LG from HG tumors were similar, and both better than their respective means. 3 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2018. © 2018 International Society for Magnetic Resonance in Medicine.

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.

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.

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

An Ultra-Low Power Charge Redistribution Successive Approximation Register A/D Converter for Biomedical Applications.

PubMed

Koppa, Santosh; Mohandesi, Manouchehr; John, Eugene

2016-12-01

Power consumption is one of the key design constraints in biomedical devices such as pacemakers that are powered by small non rechargeable batteries over their entire life time. In these systems, Analog to Digital Convertors (ADCs) are used as interface between analog world and digital domain and play a key role. In this paper we present the design of an 8-bit Charge Redistribution Successive Approximation Register (CR-SAR) analog to digital converter in standard TSMC 0.18μm CMOS technology for low power and low data rate devices such as pacemakers. The 8-bit optimized CR-SAR ADC achieves low power of less than 250nW with conversion rate of 1KB/s. This ADC achieves integral nonlinearity (INL) and differential nonlinearity (DNL) less than 0.22 least significant bit (LSB) and less than 0.04 LSB respectively as compared to the standard requirement for the INL and DNL errors to be less than 0.5 LSB. The designed ADC operates at 1V supply voltage converting input ranging from 0V to 250mV.

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.

A study of T2-weighted MR image texture features and diffusion-weighted MR image features for computer-aided diagnosis of prostate cancer

NASA Astrophysics Data System (ADS)

Peng, Yahui; Jiang, Yulei; Antic, Tatjana; Giger, Maryellen L.; Eggener, Scott; Oto, Aytekin

2013-02-01

The purpose of this study was to study T2-weighted magnetic resonance (MR) image texture features and diffusionweighted (DW) MR image features in distinguishing prostate cancer (PCa) from normal tissue. We collected two image datasets: 23 PCa patients (25 PCa and 23 normal tissue regions of interest [ROIs]) imaged with Philips MR scanners, and 30 PCa patients (41 PCa and 26 normal tissue ROIs) imaged with GE MR scanners. A radiologist drew ROIs manually via consensus histology-MR correlation conference with a pathologist. A number of T2-weighted texture features and apparent diffusion coefficient (ADC) features were investigated, and linear discriminant analysis (LDA) was used to combine select strong image features. Area under the receiver operating characteristic (ROC) curve (AUC) was used to characterize feature effectiveness in distinguishing PCa from normal tissue ROIs. Of the features studied, ADC 10th percentile, ADC average, and T2-weighted sum average yielded AUC values (+/-standard error) of 0.95+/-0.03, 0.94+/-0.03, and 0.85+/-0.05 on the Phillips images, and 0.91+/-0.04, 0.89+/-0.04, and 0.70+/-0.06 on the GE images, respectively. The three-feature combination yielded AUC values of 0.94+/-0.03 and 0.89+/-0.04 on the Phillips and GE images, respectively. ADC 10th percentile, ADC average, and T2-weighted sum average, are effective in distinguishing PCa from normal tissue, and appear robust in images acquired from Phillips and GE MR scanners.

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.

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.

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.

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

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.

Big Data Tools as Applied to ATLAS Event Data

NASA Astrophysics Data System (ADS)

Vukotic, I.; Gardner, R. W.; Bryant, L. A.

2017-10-01

Big Data technologies have proven to be very useful for storage, processing and visualization of derived metrics associated with ATLAS distributed computing (ADC) services. Logfiles, database records, and metadata from a diversity of systems have been aggregated and indexed to create an analytics platform for ATLAS ADC operations analysis. Dashboards, wide area data access cost metrics, user analysis patterns, and resource utilization efficiency charts are produced flexibly through queries against a powerful analytics cluster. Here we explore whether these techniques and associated analytics ecosystem can be applied to add new modes of open, quick, and pervasive access to ATLAS event data. Such modes would simplify access and broaden the reach of ATLAS public data to new communities of users. An ability to efficiently store, filter, search and deliver ATLAS data at the event and/or sub-event level in a widely supported format would enable or significantly simplify usage of machine learning environments and tools like Spark, Jupyter, R, SciPy, Caffe, TensorFlow, etc. Machine learning challenges such as the Higgs Boson Machine Learning Challenge, the Tracking challenge, Event viewers (VP1, ATLANTIS, ATLASrift), and still to be developed educational and outreach tools would be able to access the data through a simple REST API. In this preliminary investigation we focus on derived xAOD data sets. These are much smaller than the primary xAODs having containers, variables, and events of interest to a particular analysis. Being encouraged with the performance of Elasticsearch for the ADC analytics platform, we developed an algorithm for indexing derived xAOD event data. We have made an appropriate document mapping and have imported a full set of standard model W/Z datasets. We compare the disk space efficiency of this approach to that of standard ROOT files, the performance in simple cut flow type of data analysis, and will present preliminary results on its scaling characteristics with different numbers of clients, query complexity, and size of the data retrieved.

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.

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

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.

Antibody-drug conjugates for cancer therapy: The technological and regulatory challenges of developing drug-biologic hybrids.

PubMed

Hamilton, Gregory S

2015-09-01

Antibody-drug conjugates (ADCs) are a new class of therapeutic agents that combine the targeting ability of monoclonal antibodies (mAbs) with small molecule drugs. The combination of a mAb targeting a cancer-specific antigen with a cytotoxin has tremendous promise as a new type of targeted cancer therapy. Two ADCs have been approved and many more are in clinical development, suggesting that this new class of drugs is coming to the forefront. Because of their unique nature as biologic-small drug hybrids, ADCs are challenging to develop, from both the scientific and regulatory perspectives. This review discusses both these aspects in current practice, and surveys the current state of the art of ADC drug development. Copyright © 2015 The International Alliance for Biological Standardization. Published by Elsevier Ltd. All rights reserved.

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.

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

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.

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.

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.

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.

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.

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.

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.

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.

Use of diffusion-weighted MRI to modify radiosurgery planning in brain metastases may reduce local recurrence.

PubMed

Zakaria, Rasheed; Pomschar, Andreas; Jenkinson, Michael D; Tonn, Jörg-Christian; Belka, Claus; Ertl-Wagner, Birgit; Niyazi, Maximilian

2017-02-01

Stereotactic radiosurgery (SRS) is an effective and well tolerated treatment for selected brain metastases; however, local recurrence still occurs. We investigated the use of diffusion weighted MRI (DWI) as an adjunct for SRS treatment planning in brain metastases. Seventeen consecutive patients undergoing complete surgical resection of a solitary brain metastasis underwent image analysis retrospectively. SRS treatment plans were generated based on standard 3D post-contrast T1-weighted sequences at 1.5T and then separately using apparent diffusion coefficient (ADC) maps in a blinded fashion. Control scans immediately post operation confirmed complete tumour resection. Treatment plans were compared to one another and with volume of local recurrence at progression quantitatively and qualitatively by calculating the conformity index (CI), the overlapping volume as a proportion of the total combined volume, where 1 = identical plans and 0 = no conformation whatsoever. Gross tumour volumes (GTVs) using ADC and post-contrast T1-weighted sequences were quantitatively the same (related samples Wilcoxon signed rank test = -0.45, p = 0.653) but showed differing conformations (CI 0.53, p < 0.001). The diffusion treatment volume (DTV) obtained by combining the two target volumes was significantly greater than the treatment volume based on post contrast T1-weighted MRI alone, both quantitatively (median 13.65 vs. 9.52 cm 3 , related samples Wilcoxon signed rank test p < 0.001) and qualitatively (CI 0.74, p = 0.001). This DTV covered a greater volume of subsequent tumour recurrence than the standard plan (median 3.53 cm 3 vs. 3.84 cm 3 , p = 0.002). ADC maps may be a useful tool in addition to the standard post-contrast T1-weighted sequence used for SRS planning.

[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.

Histogram analysis derived from apparent diffusion coefficient (ADC) is more sensitive to reflect serological parameters in myositis than conventional ADC analysis.

PubMed

Meyer, Hans Jonas; Emmer, Alexander; Kornhuber, Malte; Surov, Alexey

2018-05-01

Diffusion-weighted imaging (DWI) has the potential of being able to reflect histopathology architecture. A novel imaging approach, namely histogram analysis, is used to further characterize tissues on MRI. The aim of this study was to correlate histogram parameters derived from apparent diffusion coefficient (ADC) maps with serological parameters in myositis. 16 patients with autoimmune myositis were included in this retrospective study. DWI was obtained on a 1.5 T scanner by using the b-values of 0 and 1000 s mm - 2 . Histogram analysis was performed as a whole muscle measurement by using a custom-made Matlab-based application. The following ADC histogram parameters were estimated: ADCmean, ADCmax, ADCmin, ADCmedian, ADCmode, and the following percentiles ADCp10, ADCp25, ADCp75, ADCp90, as well histogram parameters kurtosis, skewness, and entropy. In all patients, the blood sample was acquired within 3 days to the MRI. The following serological parameters were estimated: alanine aminotransferase, aspartate aminotransferase, creatine kinase, lactate dehydrogenase, C-reactive protein (CRP) and myoglobin. All patients were screened for Jo1-autobodies. Kurtosis correlated inversely with CRP (p = -0.55 and 0.03). Furthermore, ADCp10 and ADCp90 values tended to correlate with creatine kinase (p = -0.43, 0.11, and p = -0.42, = 0.12 respectively). In addition, ADCmean, p10, p25, median, mode, and entropy were different between Jo1-positive and Jo1-negative patients. ADC histogram parameters are sensitive for detection of muscle alterations in myositis patients. Advances in knowledge: This study identified that kurtosis derived from ADC maps is associated with CRP in myositis patients. Furthermore, several ADC histogram parameters are statistically different between Jo1-positive and Jo1-negative patients.

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

Evaluation of radiation necrosis and malignant glioma in rat models using diffusion tensor MR imaging

PubMed Central

Wang, Silun; Chen, Yifei; Lal, Bachchu; Ford, Eric; Tryggestad, Erik; Armour, Michael; Yan, Kun; Laterra, John; Zhou, Jinyuan

2011-01-01

Standard MRI cannot distinguish between radiation necrosis and tumor progression; however, this distinction is critical in the assessment of tumor response to therapy. In this study, one delayed radiation necrosis model (dose, 40 Gy; radiation field, 10 × 10 mm2; n = 13) and two orthotopic glioma models in rats (9L gliosarcoma, n = 8; human glioma xenografts, n = 5) were compared using multiple DTI indices. A visible isotropic apparent diffusion coefficient (ADC) pattern was observed in the lesion due to radiation necrosis, which consisted of a hypointense central zone and a hyperintense peripheral zone. There were significantly lower ADC, parallel diffusivity, and perpendicular diffusivity in the necrotic central zone than in the peripheral zone (all p < 0.001). When radiation-induced necrosis was compared with viable tumor, radiation necrosis had significantly lower ADC than 9L gliosarcoma and human glioma xenografts (both p < 0.01) in the central zone, and significantly lower FA than 9L gliosarcoma (p = 0.005) and human glioma xenografts (p = 0.012) in the peripheral zone. Histological analysis revealed parenchymal coagulative necrosis in the central zone, and damaged vessels and reactive astrogliosis in the peripheral zone. These data suggest that qualitative and quantitative analysis of the DTI maps can provide useful information by which to distinguish between radiation necrosis and viable glioma. PMID:21948114

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

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.

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

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.

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.

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.

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.

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.

Cost-effectiveness analysis of treatment alternatives for beef bulls with preputial prolapse.

PubMed

Kasari, T R; McGrann, J M; Hooper, R N

1997-10-01

To develop an economic model for comparing cost-effectiveness of medical and surgical treatment versus replacement of beef bulls with preputial prolapse. Economic analysis. Estimates determined from medical records of bulls treated for preputial prolapse at our hospital and from information about treatment of bulls published elsewhere. Annual depreciation cost for treatment (ADC(T)) and replacement (ADC(R)) were calculated. Total investment for an injured bull equaled the sum of salvage value, maintenance cost, and expected cost of the treatment option under consideration. Total investment for a replacement bull was purchase price. Net present value of cost was calculated for each year of bull use. Sensitivity analyses were constructed to determine the value that would warrant treatment of an injured bull. The decision to treat was indicated when ADC(T) was less than ADC(R). In our example, it was more cost-effective for owners to cull an injured bull. The ADC(R) was $97 less than ADC(T) for medical treatment ($365 vs $462) and $280 less than ADC(T) for surgical treatment ($365 vs $645). Likewise, net present value of cost values indicated that it was more cost-effective for owners to cull an injured bull. Sensitivity analysis indicated treatment decisions were justified on the basis of replacement value or planned number of breeding seasons remaining for the bull. The model described here can be used by practitioners to provide an objective basis to guide decision making of owners who seek advice on whether to treat or replace bulls with preputial prolapse.

ADC histogram analysis of muscle lymphoma - Correlation with histopathology in a rare entity.

PubMed

Meyer, Hans-Jonas; Pazaitis, Nikolaos; Surov, Alexey

2018-06-21

Diffusion weighted imaging (DWI) is able to reflect histopathology architecture. A novel imaging approach, namely histogram analysis, is used to further characterize lesion on MRI. The purpose of this study is to correlate histogram parameters derived from apparent diffusion coefficient- (ADC) maps with histopathology parameters in muscle lymphoma. Eight patients (mean age 64.8 years, range 45-72 years) with histopathologically confirmed muscle lymphoma were retrospectively identified. Cell count, total nucleic and average nucleic areas were estimated using ImageJ. Additionally, Ki67-index was calculated. DWI was obtained on a 1.5T scanner by using the b values of 0 and 1000 s/mm2. Histogram analysis was performed as a whole lesion measurement by using a custom-made Matlabbased application. The correlation analysis revealed statistically significant correlation between cell count and ADCmean (p=-0.76, P=0.03) as well with ADCp75 (p=-0.79, P=0.02). Kurtosis and entropy correlated with average nucleic area (p=-0.81, P=0.02, p=0.88, P=0.007, respectively). None of the analyzed ADC parameters correlated with total nucleic area and with Ki67-index. This study identified significant correlations between cellularity and histogram parameters derived from ADC maps in muscle lymphoma. Thus, histogram analysis parameters reflect histopathology in muscle tumors. Advances in knowledge: Whole lesion ADC histogram analysis is able to reflect histopathology parameters in muscle lymphomas.

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

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.

[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.

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.

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.

Potential of MR histogram analyses for prediction of response to chemotherapy in patients with colorectal hepatic metastases.

PubMed

Liang, He-Yue; Huang, Ya-Qin; Yang, Zhao-Xia; Ying-Ding; Zeng, Meng-Su; Rao, Sheng-Xiang

2016-07-01

To determine if magnetic resonance imaging (MRI) histogram analyses can help predict response to chemotherapy in patients with colorectal hepatic metastases by using response evaluation criteria in solid tumours (RECIST1.1) as the reference standard. Standard MRI including diffusion-weighted imaging (b=0, 500 s/mm(2)) was performed before chemotherapy in 53 patients with colorectal hepatic metastases. Histograms were performed for apparent diffusion coefficient (ADC) maps, arterial, and portal venous phase images; thereafter, mean, percentiles (1st, 10th, 50th, 90th, 99th), skewness, kurtosis, and variance were generated. Quantitative histogram parameters were compared between responders (partial and complete response, n=15) and non-responders (progressive and stable disease, n=38). Receiver operator characteristics (ROC) analyses were further analyzed for the significant parameters. The mean, 1st percentile, 10th percentile, 50th percentile, 90th percentile, 99th percentile of the ADC maps were significantly lower in responding group than that in non-responding group (p=0.000-0.002) with area under the ROC curve (AUCs) of 0.76-0.82. The histogram parameters of arterial and portal venous phase showed no significant difference (p>0.05) between the two groups. Histogram-derived parameters for ADC maps seem to be a promising tool for predicting response to chemotherapy in patients with colorectal hepatic metastases. • ADC histogram analyses can potentially predict chemotherapy response in colorectal liver metastases. • Lower histogram-derived parameters (mean, percentiles) for ADC tend to have good response. • MR enhancement histogram analyses are not reliable to predict response.

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.

Whole-lesion ADC histogram and texture analysis in predicting recurrence of cervical cancer treated with CCRT.

PubMed

Meng, Jie; Zhu, Lijing; Zhu, Li; Xie, Li; Wang, Huanhuan; Liu, Song; Yan, Jing; Liu, Baorui; Guan, Yue; He, Jian; Ge, Yun; Zhou, Zhengyang; Yang, Xiaofeng

2017-11-03

To explore the value of whole-lesion apparent diffusion coefficient (ADC) histogram and texture analysis in predicting tumor recurrence of advanced cervical cancer treated with concurrent chemo-radiotherapy (CCRT). 36 women with pathologically confirmed advanced cervical squamous carcinomas were enrolled in this prospective study. 3.0 T pelvic MR examinations including diffusion weighted imaging (b = 0, 800 s/mm 2 ) were performed before CCRT (pre-CCRT) and at the end of 2nd week of CCRT (mid-CCRT). ADC histogram and texture features were derived from the whole volume of cervical cancers. With a mean follow-up of 25 months (range, 11 ∼ 43), 10/36 (27.8%) patients ended with recurrence. Pre-CCRT 75th, 90th, correlation, autocorrelation and mid-CCRT ADC mean , 10th, 25th, 50th, 75th, 90th, autocorrelation can effectively differentiate the recurrence from nonrecurrence group with area under the curve ranging from 0.742 to 0.850 (P values range, 0.001 ∼ 0.038). Pre- and mid-treatment whole-lesion ADC histogram and texture analysis hold great potential in predicting tumor recurrence of advanced cervical cancer treated with CCRT.

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.

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.

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 Central

Tsuchiya, Naoko; Doai, Mariko; Usuda, Katsuo; Uramoto, Hidetaka

2017-01-01

Purpose 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. Materials and methods 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. Results 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. Conclusions ADC histogram analyses on the basis of the entire tumor volume are able to stratify NSCLCs' tumor grade, lymphovascular invasion and pleural invasion. PMID:28207858

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.

Assessment of the Focal Hepatic Lesions Using Diffusion Tensor Magnetic Resonance Imaging

PubMed Central

Oussous, Siham Ait; Boujraf, Saïd; Kamaoui, Imane

2016-01-01

The goal is assessing the diffusion magnetic resonance imaging (dMRI) method efficiency in characterizing focal hepatic lesions (FHLs). About 28-FHL patients were studied in Radiology and Clinical Imaging Department of our University Hospital using 1.5 Tesla MRI system between January 2010 and June 2011. Patients underwent hepatic MRI consisting of dynamic T1- and T2-weighted imaging. The dMRI was performed with b-values of 200 s/mm2 and 600 s/mm2. About 42 lesions measuring more than 1 cm were studied including the variation of the signal according to the b-value and the apparent diffusion coefficient (ADC). The diagnostic imaging reference was based on standard MRI techniques data for typical lesions and on histology after surgical biopsy for atypical lesions. About 38 lesions were assessed including 13 benign lesions consisting of 1 focal nodular hyperplasia, 8 angiomas, and 4 cysts. About 25 malignant lesions included 11 hepatocellular carcinoma, 9 hepatic metastases, 1 cholangiocarcinoma, and 4 lymphomas. dMRI of soft lesions demonstrated higher ADC of 2.26 ± 0.75 mm2/s, whereas solid lesions showed lower ADC 1.19 ± 0.33 mm2/s with significant difference (P = 0.05). Discrete values collections were noticed. These results were correlated to standard MRI and histological findings. Sensitivity of 93% and specificity of 84% were found in diagnoses of malignant tumors with an ADC threshold of 1.6 × 10−3 mm2/s. dMRI is important characterization method of FHL. However, it should not be used as single criteria of hepatic lesions malignity. MRI, clinical, and biological data must be correlated. Significant difference was found between benign and solid malignant lesions without threshold ADC values. Hence, it is difficult to confirm ADC threshold differentiating the lesion classification. PMID:27186537

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.

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

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.

An ultra low-power front-end IC for wearable health monitoring system.

PubMed

Yu-Pin Hsu; Zemin Liu; Hella, Mona M

2016-08-01

This paper presents a low-power front-end IC for wearable health monitoring systems. The IC, designed in a standard 0.13μm CMOS technology, fully integrates a low-noise analog front-end (AFE) to process the weak bio-signals, followed by an analog-to-digital converter (ADC) to digitize the extracted signals. An AC-coupled driving buffer, that interfaces between the AFE and the ADC is introduced to scale down the power supply of the ADC. The power consumption decreases by 50% compared to the case without power supply scaling. The AFE passes signals from 0.5Hz to 280Hz and from 0.7Hz to 160Hz with a simulated input referred noise of 1.6μVrms and achieves a maximum gain of 35dB/41dB respectively, with a noise-efficiency factor (NEF) of the AFE is 1. The 8-bit ADC achieves a simulated 7.96-bit resolution at 10KS/s sampling rate under 0.5V supply voltage. The overall system consumes only 0.86μW at dual supply voltages of 1V (AFE) and 0.5 V (ADC).

High-resolution diffusion and relaxation-edited magic angle spinning 1H NMR spectroscopy of intact liver tissue.

PubMed

Rooney, O M; Troke, J; Nicholson, J K; Griffin, J L

2003-11-01

High-resolution magic angle spinning (HRMAS) (1)H NMR spectroscopy is ideal for monitoring the metabolic environment within tissues, particularly when spectra are weighted by physical properties such as T(1) and T(2) relaxation times and apparent diffusion coefficients (ADCs). In this study, spectral-editing using T(1) and T(2) relaxation times and ADCs at variable diffusion times was used in conjunction with HRMAS (1)H NMR spectroscopy at 14.1 T in liver tissue. To enhance the sensitivity of ADC measurements to low molecular weight metabolites a T(2) spin echo was included in a standard stimulated gradient spin-echo sequence. Fatty liver induced in rats by chronic orotic acid feeding was investigated using this modified sequence. An increase in the combined ADC for the co-resonant peaks glucose, betaine, and TMAO during fatty liver disease was detected (ADCs = 0.60 +/- 0.11 and 0.35 +/- 0.1 * 10(-9) m(2)s(-1) (n = 3) for rats fed with and without orotic acid), indicative of a reduction in glucose and betaine and an increase in TMAO. Copyright 2003 Wiley-Liss, Inc.

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.

Comparison of a hybrid medication distribution system to simulated decentralized distribution models.

PubMed

Gray, John P; Ludwig, Brad; Temple, Jack; Melby, Michael; Rough, Steve

2013-08-01

The results of a study to estimate the human resource and cost implications of changing the medication distribution model at a large medical center are presented. A two-part study was conducted to evaluate alternatives to the hospital's existing hybrid distribution model (64% of doses dispensed via cart fill and 36% via automated dispensing cabinets [ADCs]). An assessment of nurse, pharmacist, and pharmacy technician workloads within the hybrid system was performed through direct observation, with time standards calculated for each dispensing task; similar time studies were conducted at a comparator hospital with a decentralized medication distribution system involving greater use of ADCs. The time study data were then used in simulation modeling of alternative distribution scenarios: one involving no use of cart fill, one involving no use of ADCs, and one heavily dependent on ADC dispensing (89% via ADC and 11% via cart fill). Simulation of the base-case and alternative scenarios indicated that as the modeled percentage of doses dispensed from ADCs rose, the calculated pharmacy technician labor requirements decreased, with a proportionately greater increase in the nursing staff workload. Given that nurses are a higher-cost resource than pharmacy technicians, the projected human resource opportunity cost of transitioning from the hybrid system to a decentralized system similar to the comparator facility's was estimated at $229,691 per annum. Based on the simulation results, it was decided that a transition from the existing hybrid medication distribution system to a more ADC-dependent model would result in an unfavorable shift in staff skill mix and corresponding human resource costs at the medical center.

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.

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.

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.

Hybrid [¹⁸F]-FDG PET/MRI including non-Gaussian diffusion-weighted imaging (DWI): preliminary results in non-small cell lung cancer (NSCLC).

PubMed

Heusch, Philipp; Köhler, Jens; Wittsack, Hans-Joerg; Heusner, Till A; Buchbender, Christian; Poeppel, Thorsten D; Nensa, Felix; Wetter, Axel; Gauler, Thomas; Hartung, Verena; Lanzman, Rotem S

2013-11-01

To assess the feasibility of non-Gaussian DWI as part of a FDG-PET/MRI protocol in patients with histologically proven non-small cell lung cancer. 15 consecutive patients with histologically proven NSCLC (mean age 61 ± 11 years) were included in this study and underwent whole-body FDG-PET/MRI following whole-body FDG-PET/CT. As part of the whole-body FDG-PET/MRI protocol, an EPI-sequence with 5 b-values (0, 100, 500, 1000 and 2000 s/mm(2)) was acquired for DWI of the thorax during free-breathing. Volume of interest (VOI) measurements were performed to determine the maximum and mean standardized uptake value (SUV(max); SUV(mean)). A region of interest (ROI) was manually drawn around the tumor on b=0 images and then transferred to the corresponding parameter maps to assess ADC(mono), D(app) and K(app). To assess the goodness of the mathematical fit R(2) was calculated for monoexponential and non-Gaussian analysis. Spearman's correlation coefficients were calculated to compare SUV values and diffusion coefficients. A Student's t-test was performed to compare the monoexponential and non-Gaussian diffusion fitting (R(2)). T staging was equal between FDG-PET/CT and FDG-PET/MRI in 12 of 15 patients. For NSCLC, mean ADC(mono) was 2.11 ± 1.24 × 10(-3) mm(2)/s, Dapp was 2.46 ± 1.29 × 10(-3) mm(2)/s and mean Kapp was 0.70 ± 0.21. The non-Gaussian diffusion analysis (R(2)=0.98) provided a significantly better mathematical fitting to the DWI signal decay than the monoexponetial analysis (R(2)=0.96) (p<0.001). SUV(max) and SUV(mean) of NSCLC was 13.5 ± 7.6 and 7.9 ± 4.3 for FDG-PET/MRI. ADC(mono) as well as Dapp exhibited a significant inverse correlation with the SUV(max) (ADC(mono): R=-0.67; p<0.01; Dapp: R=-0.69; p<0.01) as well as with SUV(mean) assessed by FDG-PET/MRI (ADC(mono): R=-0.66; p<0.01; Dapp: R=-0.69; p<0.01). Furthermore, Kapp exhibited a significant correlation with SUV(max) (R=0.72; p<0.05) and SUV(mean) as assessed by FDG-PET/MRI (R=0.71; p<0.005). Simultaneous PET and non-Gaussian diffusion acquisitions are feasible. Non-Gaussian diffusion parameters show a good correlation with SUV and might provide additional information beyond monoexponential ADC, especially as non-Gaussian diffusion exhibits better mathematical fitting to the decay of the diffusion signal than monoexponential DWI. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Free-breathing diffusion-weighted imaging for the assessment of inflammatory activity in Crohn's disease.

PubMed

Kiryu, Shigeru; Dodanuki, Keiichi; Takao, Hidemasa; Watanabe, Makoto; Inoue, Yusuke; Takazoe, Masakazu; Sahara, Rikisaburo; Unuma, Kiyohito; Ohtomo, Kuni

2009-04-01

To investigate the application of free-breathing diffusion-weighted MR imaging (DWI) to the assessment of disease activity in Crohn's disease. Thirty-one patients with Crohn's disease were investigated using free-breathing DWI without special patient preparation or IV or intraluminal contrast agent. The bowel was divided into seven segments, and disease activity was assessed visually on DWI. For quantitative analysis, the apparent diffusion coefficient (ADC) was measured in each segment. The findings of a conventional barium study or surgery were regarded as the gold standard for evaluating the diagnostic ability of DWI to assess disease activity. Upon visual assessment, the sensitivity, specificity, and accuracy for the detection of disease-active segments were 86.0, 81.4, and 82.4%, respectively. In the quantitative assessment, the ADC value in the disease-active area was lower than that in disease-inactive area in small and large bowels (1.61 +/- 0.44 x 10(-3) mm(2)/s versus 2.56 +/- 0.51 x 10(-3) mm(2)/s in small bowel and 1.52 +/- 0.43 x 10(-3) mm(2)/s versus 2.31 +/- 0.59 x 10(-3) mm(2)/s in large bowel, respectively, P<0.001). Free-breathing DWI is useful in the assessment of Crohn's disease. The accuracy of DWI is high in evaluating disease activity, especially in the small bowel, and the ADC may facilitate quantitative analysis of disease activity.

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

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

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

ATLAS Distributed Computing Monitoring tools during the LHC Run I

NASA Astrophysics Data System (ADS)

Schovancová, J.; Campana, S.; Di Girolamo, A.; Jézéquel, S.; Ueda, I.; Wenaus, T.; Atlas Collaboration

2014-06-01

This contribution summarizes evolution of the ATLAS Distributed Computing (ADC) Monitoring project during the LHC Run I. The ADC Monitoring targets at the three groups of customers: ADC Operations team to early identify malfunctions and escalate issues to an activity or a service expert, ATLAS national contacts and sites for the real-time monitoring and long-term measurement of the performance of the provided computing resources, and the ATLAS Management for long-term trends and accounting information about the ATLAS Distributed Computing resources. During the LHC Run I a significant development effort has been invested in standardization of the monitoring and accounting applications in order to provide extensive monitoring and accounting suite. ADC Monitoring applications separate the data layer and the visualization layer. The data layer exposes data in a predefined format. The visualization layer is designed bearing in mind visual identity of the provided graphical elements, and re-usability of the visualization bits across the different tools. A rich family of various filtering and searching options enhancing available user interfaces comes naturally with the data and visualization layer separation. With a variety of reliable monitoring data accessible through standardized interfaces, the possibility of automating actions under well defined conditions correlating multiple data sources has become feasible. In this contribution we discuss also about the automated exclusion of degraded resources and their automated recovery in various activities.

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.

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

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.

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

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.

Factor Analysis of the Alcohol and Drug Confrontation Scale (ADCS)

PubMed Central

Polcin, Douglas L.; Galloway, Gantt P.; Bostrom, Alan; Greenfield, Thomas K.

2007-01-01

The Alcohol and Drug Confrontation Scale (ADCS) is a 72-item instrument that defines confrontation as an individual being told “bad things” might happen if they do not make changes to address alcohol or drug problems or maintain sobriety. Preliminary assessment of the ADCS using substance abusers entering SLH's revealed: 1) Scale items were frequently endorsed; 2) Confrontation was often experienced as accurate and helpful; and 3) Confronters' statements were viewed supportive and accurate. This study reports the results of a factor analysis on a larger sample 179 participants using baseline and 6 month follow-up data. Results yielded a clear two factor solution: 1) Internal Support (alpha = 0.80) and 2) External Intensity (alpha = 0.63). The two factors accounted for 58% of the variance. The ADCS offers a fresh and broader view of confrontation that can be reliably measured. PMID:17270360

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%.

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.

Malignant pleural disease: diagnosis by using diffusion-weighted and dynamic contrast-enhanced MR imaging--initial experience.

PubMed

Coolen, Johan; De Keyzer, Frederik; Nafteux, Philippe; De Wever, Walter; Dooms, Christophe; Vansteenkiste, Johan; Roebben, Ilse; Verbeken, Eric; De Leyn, Paul; Van Raemdonck, Dirk; Nackaerts, Kristiaan; Dymarkowski, Steven; Verschakelen, Johny

2012-06-01

To investigate the use of diffusion-weighted (DW) imaging for differentiating benign lesions from malignant pleural disease (MPD) and to retrospectively assess dynamic contrast material-enhanced (DCE) magnetic resonance (MR) imaging acquisitions to find out whether combining these measurements with DW imaging could improve the diagnostic value of DW imaging. This study was approved by the local ethics committee, and all patients provided written informed consent. Thirty-one consecutive patients with pleural abnormalities suspicious for MPD underwent whole-body positron emission tomography (PET)/computed tomography (CT) and thorax MR examinations. Diagnostic thoracoscopy with histopathologic analysis of pleural biopsies served as the reference standard. First-line evaluation of each suspicious lesion was performed by using the apparent diffusion coefficient (ADC) calculated from the DW image, and the optimal cutoff value was found by using receiver operating characteristic curve analysis. Afterward, DCE MR imaging data were used to improve the diagnosis in the range of ADCs where DW imaging results were equivocal. Sensitivity, specificity, and accuracy of PET/CT for diagnosis of MPD were 100%, 35.3%, and 64.5%. The optimal ADC threshold to differentiate benign lesions from MPD with DW MR imaging was 1.52 × 10(-3) mm(2)/sec, with sensitivity, specificity, and accuracy of 71.4%, 100%, and 87.1%, respectively. This result could be improved to 92.8%, 94.1%, and 93.5%, respectively, when DCE MR imaging data were included in those cases where ADC was between 1.52 and 2.00 × 10(-3) mm(2)/sec. A total of 20 patients had disease diagnosed correctly, nine had disease diagnosed incorrectly, and two cases were undetermined with PET/CT. DW imaging helped stage disease correctly in 27 patients and incorrectly in four. The undetermined cases at PET/CT were correctly diagnosed at MR imaging. DW imaging is a promising tool for differentiating MPD from benign lesions, with high accuracy, and supplementation with DCE MR imaging seems to further improve sensitivity.

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.

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.

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

Comparison of Utility of Histogram Apparent Diffusion Coefficient and R2* for Differentiation of Low-Grade From High-Grade Clear Cell Renal Cell Carcinoma.

PubMed

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

2015-08-01

The purpose of this study was to compare histogram analysis of apparent diffusion coefficient (ADC) and R2* for differentiating low-grade from high-grade clear cell renal cell carcinoma (RCC). Forty-six patients with pathologically confirmed clear cell RCC underwent preoperative BOLD and DWI MRI of the kidneys. ADCs based on the entire tumor volume were calculated with b value combinations of 0 and 800 s/mm(2). ROI-based R2* was calculated with eight TE combinations of 6.7-22.8 milliseconds. Histogram analysis of tumor ADCs and R2* values was performed to obtain mean; median; width; and fifth, 10th, 90th, and 95th percentiles and histogram inhomogeneity, kurtosis, and skewness for all lesions. Thirty-three low-grade and 13 high-grade clear cell RCCs were found at pathologic examination. The TNM classification and tumor volume of clear cell RCC significantly correlated with histogram ADC and R2* (ρ = -0.317 to 0.506; p < 0.05). High-grade clear cell RCC had significantly lower mean, median, and 10th percentile ADCs but higher inhomogeneity and median R2* than low-grade clear cell RCC (all p < 0.05). Compared with other histogram ADC and R2* indexes, 10th percentile ADC had the highest accuracy (91.3%) in discriminating low- from high-grade clear cell RCC. R2* in discriminating hemorrhage was achieved with a threshold of 68.95 Hz. At this threshold, high-grade clear cell RCC had a significantly higher prevalence of intratumor hemorrhage (high-grade, 76.9%; low-grade, 45.4%; p < 0.05) and larger hemorrhagic area than low-grade clear cell RCC (high-grade, 34.9% ± 31.6%; low-grade, 8.9 ± 16.8%; p < 0.05). A close relation was found between MRI indexes and pathologic findings. Histogram analysis of ADC and R2* allows differentiation of low- from high-grade clear cell RCC with high accuracy.

Correlation between tissue metabolism and cellularity assessed by standardized uptake value and apparent diffusion coefficient in peritoneal metastasis.

PubMed

Yu, Xue; Lee, Elaine Yuen Phin; Lai, Vincent; Chan, Queenie

2014-07-01

To evaluate the correlation between standardized uptake value (SUV) (tissue metabolism) and apparent diffusion coefficient (ADC) (water diffusivity) in peritoneal metastases. Patients with peritoneal dissemination detected on (18)F-fluorodeoxyglucose positron emission tomography combined with computed tomography (FDG-PET/CT) were prospectively recruited for MRI examinations with informed consent and the study was approved by the local Institutional Review Board. FDG-PET/CT, diffusion-weighted imaging (DWI), MRI, and DWI/MRI images were independently reviewed by two radiologists based on visual analysis. SUVmax/SUVmean and ADCmin/ADCmean were obtained manually by drawing ROIs over the peritoneal metastases on FDG-PET/CT and DWI, respectively. Diagnostic characteristics of each technique were evaluated. Pearson's coefficient and McNemar and Kappa tests were used for statistical analysis. Eight patients were recruited for this prospective study and 34 peritoneal metastases were evaluated. ADCmean was significantly and negatively correlated with SUVmax (r = -0.528, P = 0.001) and SUVmean (r = -0.548, P = 0.001). ADCmin had similar correlation with SUVmax (r = -0.508, P = 0.002) and SUVmean (r = -0.513, P = 0.002). DWI/MRI had high diagnostic performance (accuracy = 98%) comparable to FDG-PET/CT, in peritoneal metastasis detection. Kappa values were excellent for all techniques. There was a significant inverse correlation between SUV and ADC. © 2013 Wiley Periodicals, Inc.

Tissue microstructural changes are independently associated with cognitive impairment in cerebral amyloid angiopathy.

PubMed

Viswanathan, Anand; Patel, Pratik; Rahman, Rosanna; Nandigam, R N Kaveer; Kinnecom, Catherine; Bracoud, Luc; Rosand, Jonathan; Chabriat, Hugues; Greenberg, Steven M; Smith, Eric E

2008-07-01

Cerebral amyloid angiopathy (CAA) is a major cause of lobar intracerebral hemorrhage and cognitive impairment and is associated with white matter hyperintensities and cerebral microbleeds. MRI diffusion tensor imaging detects microstructural tissue damage in advanced CAA even in areas that appear normal on conventional MRI. We hypothesized that higher global mean apparent diffusion coefficient (mean ADC), reflecting a higher amount of chronic tissue disruption caused by CAA, would be independently associated with CAA-related cognitive impairment. Preintracerebral hemorrhage cognitive impairment was systematically assessed using a standardized questionnaire (IQCODE) in 49 patients. Volume of white matter hyperintensities, number of microbleeds, and mean ADC were determined from MRIs obtained within 14.0+/-22.5 days of intracerebral hemorrhage cognitive impairment. White matter hyperintensities and mean ADC were measured in the hemisphere uninvolved by intracerebral hemorrhage to avoid confounding. Preintracerebral hemorrhage cognitive impairment was identified in 10 of 49 subjects. Mean ADC was the only variable associated with preintracerebral hemorrhage cognitive impairment and was elevated in those with preintracerebral hemorrhage cognitive impairment compared with those without (12.4x10(-4) versus 11.7x10(-4) mm(2)/s; P=0.03). Mean ADC positively correlated with age but not white matter hyperintensities or number of microbleeds. In logistic regression controlling for age and visible cerebral atrophy, mean ADC was independently associated with preintracerebral hemorrhage cognitive impairment (OR per 1x10(-4) mm(2)/s increase=2.45, 95% CI 1.11 to 5.40, P=0.04). Mean ADC is independently associated with preintracerebral hemorrhage cognitive impairment in CAA. The lack of correlation with other MRI markers of CAA suggests that mean ADC may be sensitive to distinct aspects of CAA pathology and its tissue consequences. These results suggest that global MRI diffusion changes are sensitive to clinically relevant microstructural alterations and may be useful markers of CAA-related tissue damage.

Tissue Microstructural Changes Are Independently Associated With Cognitive Impairment in Cerebral Amyloid Angiopathy

PubMed Central

Viswanathan, Anand; Patel, Pratik; Rahman, Rosanna; Nandigam, R.N. Kaveer; Kinnecom, Catherine; Bracoud, Luc; Rosand, Jonathan; Chabriat, Hugues; Greenberg, Steven M.; Smith, Eric E.

2009-01-01

Background and Purpose Cerebral amyloid angiopathy (CAA) is a major cause of lobar intracerebral hemorrhage and cognitive impairment and is associated with white matter hyperintensities and cerebral microbleeds. MRI diffusion tensor imaging detects microstructural tissue damage in advanced CAA even in areas that appear normal on conventional MRI. We hypothesized that higher global mean apparent diffusion coefficient (mean ADC), reflecting a higher amount of chronic tissue disruption caused by CAA, would be independently associated with CAA-related cognitive impairment. Methods Preintracerebral hemorrhage cognitive impairment was systematically assessed using a standardized questionnaire (IQCODE) in 49 patients. Volume of white matter hyperintensities, number of microbleeds, and mean ADC were determined from MRIs obtained within 14.0±22.5 days of intracerebral hemorrhage cognitive impairment. White matter hyperintensities and mean ADC were measured in the hemisphere uninvolved by intracerebral hemorrhage to avoid confounding. Results Preintracerebral hemorrhage cognitive impairment was identified in 10 of 49 subjects. Mean ADC was the only variable associated with preintracerebral hemorrhage cognitive impairment and was elevated in those with preintracerebral hemorrhage cognitive impairment compared with those without (12.4×10-4 versus 11.7×10-4 mm2/s; P=0.03). Mean ADC positively correlated with age but not white matter hyperintensities or number of microbleeds. In logistic regression controlling for age and visible cerebral atrophy, mean ADC was independently associated with preintracerebral hemorrhage cognitive impairment (OR per 1×10-4 mm2/s increase=2.45, 95% CI 1.11 to 5.40, P=0.04). Conclusions Mean ADC is independently associated with preintracerebral hemorrhage cognitive impairment in CAA. The lack of correlation with other MRI markers of CAA suggests that mean ADC may be sensitive to distinct aspects of CAA pathology and its tissue consequences. These results suggest that global MRI diffusion changes are sensitive to clinically relevant microstructural alterations and may be useful markers of CAA-related tissue damage. PMID:18436874

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.

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.

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.

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.

Simultaneous multislice diffusion-weighted MRI of the liver: Analysis of different breathing schemes in comparison to standard sequences.

PubMed

Taron, Jana; Martirosian, Petros; Erb, Michael; Kuestner, Thomas; Schwenzer, Nina F; Schmidt, Holger; Honndorf, Valerie S; Weiβ, Jakob; Notohamiprodjo, Mike; Nikolaou, Konstantin; Schraml, Christina

2016-10-01

To systematically evaluate image characteristics of simultaneous-multislice (SMS)-accelerated diffusion-weighted imaging (DWI) of the liver using different breathing schemes in comparison to standard sequences. DWI of the liver was performed in 10 healthy volunteers and 12 patients at 1.5T using an SMS-accelerated echo planar imaging sequence performed with respiratory-triggering and free breathing (SMS-RT, SMS-FB). Standard DWI sequences served as reference (STD-RT, STD-FB). Reduction of scan time by SMS-acceleration was measured. Image characteristics of SMS-DWI and STD-DWI with both breathing schemes were analyzed quantitatively (apparent diffusion coefficient [ADC], signal-to-noise ratio [SNR]) and qualitatively (5-point Likert scale, 5 = excellent). Qualitative and quantitative parameters were compared using Friedman test and Dunn-Bonferroni post-hoc method with P-values < 0.05 considered statistically significant. SMS-DWI provided diagnostic image quality in volunteers and patients both with RT and FB with a reduction of scan time of 70% (0:56 vs. 3:20 min in FB). Overall image quality did not significantly differ between FB and RT acquisition in both STD and SMS sequences (median STD-RT 5.0, STD-FB 4.5, SMS-RT: 4.75; SMS-FB: 4.5; P = 0.294). SNR in the right hepatic lobe was comparable between the four tested sequences. ADC values were significantly lower in SMS-DWI compared to STD-DWI irrespective of the breathing scheme (1.2 ± 0.2 × 10(-3) mm(2) /s vs. 1.0 ± 0.2 × 10(-3) mm(2) /s; P < 0.001). SMS-acceleration provides considerable scan time reduction for hepatic DWI with equivalent image quality compared to the STD technique both using RT and FB. Discrepancies in ADC between STD-DWI and SMS-DWI need to be considered when transferring the SMS technique to clinical routine reading. J. MAGN. RESON. IMAGING 2016;44:865-879. © 2016 International Society for Magnetic Resonance in Medicine.

Prediction of tumor differentiation using sequential PET/CT and MRI in patients with breast cancer.

PubMed

Choi, Joon Ho; Lim, Ilhan; Noh, Woo Chul; Kim, Hyun-Ah; Seong, Min-Ki; Jang, Seonah; Seol, Hyesil; Moon, Hansol; Byun, Byung Hyun; Kim, Byung Il; Choi, Chang Woon; Lim, Sang Moo

2018-05-23

The aim of this study is to assess tumor differentiation using parameters from sequential positron emission tomography/computed tomography (PET/CT) and magnetic resonance imaging (MRI) in patients with breast cancer. This retrospective study included 78 patients with breast cancer. All patients underwent sequential PET/CT and MRI. For fluorodeoxyglucose (FDG)-PET image analysis, the maximum standardized uptake value (SUV max ) of FDG was assessed at both 1 and 2 h and metabolic tumor volume (MTV) and total lesion glycolysis (TLG). The kinetic analysis of dynamic contrast-enhanced MRI parameters was performed using dynamic enhancement curves. We assessed diffusion-weighted imaging (DWI)-MRI parameters regarding apparent diffusion coefficient (ADC) values. Histologic grades 1 and 2 were classified as low-grade, and grade 3 as high-grade tumor. Forty-five lesions of 78 patients were classified as histologic grade 3, while 26 and 7 lesions were grade 2 and grade 1, respectively. Patients with high-grade tumors showed significantly lower ADC-mean values than patients with low-grade tumors (0.99 ± 0.19 vs.1.12 ± 0.32, p = 0.007). With respect to SUV max 1, MTV2.5, and TLG2.5, patients with high-grade tumors showed higher values than patients with low-grade tumors: SUV max 1 (7.92 ± 4.5 vs.6.19 ± 3.05, p = 0.099), MTV2.5 (7.90 ± 9.32 vs.4.38 ± 5.10, p = 0.095), and TLG2.5 (40.83 ± 59.17 vs.19.66 ± 26.08, p = 0.082). However, other parameters did not reveal significant differences between low-grade and high-grade malignancies. In receiver-operating characteristic (ROC) curve analysis, ADC-mean values showed the highest area under the curve of 0.681 (95%CI 0.566-0.782) for assessing high-grade malignancy. Lower ADC-mean values may predict the poor differentiation of breast cancer among diverse PET-MRI functional parameters.

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.

Histogram analysis of ADC in rectal cancer: associations with different histopathological findings including expression of EGFR, Hif1-alpha, VEGF, p53, PD1, and KI 67. A preliminary study.

PubMed

Meyer, Hans Jonas; Höhn, Annekathrin; Surov, Alexey

2018-04-06

Functional imaging modalities like Diffusion-weighted imaging are increasingly used to predict tumor behavior like cellularity and vascularity in different tumors. Histogram analysis is an emergent imaging analysis, in which every voxel is used to obtain a histogram and therefore statistically information about tumors can be provided. The purpose of this study was to elucidate possible associations between ADC histogram parameters and several immunhistochemical features in rectal cancer. Overall, 11 patients with histologically proven rectal cancer were included into the study. There were 2 (18.18%) females and 9 males with a mean age of 67.1 years. KI 67-index, expression of p53, EGFR, VEGF, and Hif1-alpha were semiautomatically estimated. The tumors were divided into PD1-positive and PD1-negative lesions. ADC histogram analysis was performed as a whole lesion measurement using an in-house matlab application. Spearman's correlation analysis revealed a strong correlation between EGFR expression and ADCmax (p=0.72, P=0.02). None of the vascular parameters (VEGF, Hif1-alpha) correlated with ADC parameters. Kurtosis and skewness correlated inversely with p53 expression (p=-0.64, P=0.03 and p=-0.81, P=0.002, respectively). ADCmedian and ADCmode correlated with Ki67 (p=-0.62, P=0.04 and p=-0.65, P=0.03, respectively). PD1-positive tumors showed statistically significant lower ADCmax values in comparison to PD1-negative tumors, 1.93 ± 0.36 vs 2.32 ± 0.47×10 -3 mm 2 /s, p=0.04. Several associations were identified between histogram parameter derived from ADC maps and EGFR, KI 67 and p53 expression in rectal cancer. Furthermore, ADCmax was different between PD1 positive and PD1 negative tumors indicating an important role of ADC parameters for possible future treatment prediction.

Histogram analysis of ADC in rectal cancer: associations with different histopathological findings including expression of EGFR, Hif1-alpha, VEGF, p53, PD1, and KI 67. A preliminary study

PubMed Central

Meyer, Hans Jonas; Höhn, Annekathrin; Surov, Alexey

2018-01-01

Functional imaging modalities like Diffusion-weighted imaging are increasingly used to predict tumor behavior like cellularity and vascularity in different tumors. Histogram analysis is an emergent imaging analysis, in which every voxel is used to obtain a histogram and therefore statistically information about tumors can be provided. The purpose of this study was to elucidate possible associations between ADC histogram parameters and several immunhistochemical features in rectal cancer. Overall, 11 patients with histologically proven rectal cancer were included into the study. There were 2 (18.18%) females and 9 males with a mean age of 67.1 years. KI 67-index, expression of p53, EGFR, VEGF, and Hif1-alpha were semiautomatically estimated. The tumors were divided into PD1-positive and PD1-negative lesions. ADC histogram analysis was performed as a whole lesion measurement using an in-house matlab application. Spearman's correlation analysis revealed a strong correlation between EGFR expression and ADCmax (p=0.72, P=0.02). None of the vascular parameters (VEGF, Hif1-alpha) correlated with ADC parameters. Kurtosis and skewness correlated inversely with p53 expression (p=-0.64, P=0.03 and p=-0.81, P=0.002, respectively). ADCmedian and ADCmode correlated with Ki67 (p=-0.62, P=0.04 and p=-0.65, P=0.03, respectively). PD1-positive tumors showed statistically significant lower ADCmax values in comparison to PD1-negative tumors, 1.93 ± 0.36 vs 2.32 ± 0.47×10−3mm2/s, p=0.04. Several associations were identified between histogram parameter derived from ADC maps and EGFR, KI 67 and p53 expression in rectal cancer. Furthermore, ADCmax was different between PD1 positive and PD1 negative tumors indicating an important role of ADC parameters for possible future treatment prediction. PMID:29719621

ADC texture—An imaging biomarker for high-grade glioma?

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

Brynolfsson, Patrik; Hauksson, Jón; Karlsson, Mikael

2014-10-15

Purpose: Survival for high-grade gliomas is poor, at least partly explained by intratumoral heterogeneity contributing to treatment resistance. Radiological evaluation of treatment response is in most cases limited to assessment of tumor size months after the initiation of therapy. Diffusion-weighted magnetic resonance imaging (MRI) and its estimate of the apparent diffusion coefficient (ADC) has been widely investigated, as it reflects tumor cellularity and proliferation. The aim of this study was to investigate texture analysis of ADC images in conjunction with multivariate image analysis as a means for identification of pretreatment imaging biomarkers. Methods: Twenty-three consecutive high-grade glioma patients were treatedmore » with radiotherapy (2 Gy/60 Gy) with concomitant and adjuvant temozolomide. ADC maps and T1-weighted anatomical images with and without contrast enhancement were collected prior to treatment, and (residual) tumor contrast enhancement was delineated. A gray-level co-occurrence matrix analysis was performed on the ADC maps in a cuboid encapsulating the tumor in coronal, sagittal, and transversal planes, giving a total of 60 textural descriptors for each tumor. In addition, similar examinations and analyses were performed at day 1, week 2, and week 6 into treatment. Principal component analysis (PCA) was applied to reduce dimensionality of the data, and the five largest components (scores) were used in subsequent analyses. MRI assessment three months after completion of radiochemotherapy was used for classifying tumor progression or regression. Results: The score scatter plots revealed that the first, third, and fifth components of the pretreatment examinations exhibited a pattern that strongly correlated to survival. Two groups could be identified: one with a median survival after diagnosis of 1099 days and one with 345 days, p = 0.0001. Conclusions: By combining PCA and texture analysis, ADC texture characteristics were identified, which seems to hold pretreatment prognostic information, independent of known prognostic factors such as age, stage, and surgical procedure. These findings encourage further studies with a larger patient cohort.« less

Modeling RP-1 fuel advanced distillation data using comprehensive two-dimensional gas chromatography coupled with time-of-flight mass spectrometry and partial least squares analysis.

PubMed

Kehimkar, Benjamin; Parsons, Brendon A; Hoggard, Jamin C; Billingsley, Matthew C; Bruno, Thomas J; Synovec, Robert E

2015-01-01

Recent efforts in predicting rocket propulsion (RP-1) fuel performance through modeling put greater emphasis on obtaining detailed and accurate fuel properties, as well as elucidating the relationships between fuel compositions and their properties. Herein, we study multidimensional chromatographic data obtained by comprehensive two-dimensional gas chromatography combined with time-of-flight mass spectrometry (GC × GC-TOFMS) to analyze RP-1 fuels. For GC × GC separations, RTX-Wax (polar stationary phase) and RTX-1 (non-polar stationary phase) columns were implemented for the primary and secondary dimensions, respectively, to separate the chemical compound classes (alkanes, cycloalkanes, aromatics, etc.), providing a significant level of chemical compositional information. The GC × GC-TOFMS data were analyzed using partial least squares regression (PLS) chemometric analysis to model and predict advanced distillation curve (ADC) data for ten RP-1 fuels that were previously analyzed using the ADC method. The PLS modeling provides insight into the chemical species that impact the ADC data. The PLS modeling correlates compositional information found in the GC × GC-TOFMS chromatograms of each RP-1 fuel, and their respective ADC, and allows prediction of the ADC for each RP-1 fuel with good precision and accuracy. The root-mean-square error of calibration (RMSEC) ranged from 0.1 to 0.5 °C, and was typically below ∼0.2 °C, for the PLS calibration of the ADC modeling with GC × GC-TOFMS data, indicating a good fit of the model to the calibration data. Likewise, the predictive power of the overall method via PLS modeling was assessed using leave-one-out cross-validation (LOOCV) yielding root-mean-square error of cross-validation (RMSECV) ranging from 1.4 to 2.6 °C, and was typically below ∼2.0 °C, at each % distilled measurement point during the ADC analysis.

Histogram analysis parameters identify multiple associations between DWI and DCE MRI in head and neck squamous cell carcinoma.

PubMed

Meyer, Hans Jonas; Leifels, Leonard; Schob, Stefan; Garnov, Nikita; Surov, Alexey

2018-01-01

Nowadays, multiparametric investigations of head and neck squamous cell carcinoma (HNSCC) are established. These approaches can better characterize tumor biology and behavior. Diffusion weighted imaging (DWI) can by means of apparent diffusion coefficient (ADC) quantitatively characterize different tissue compartments. Dynamic contrast-enhanced magnetic resonance imaging (DCE MRI) reflects perfusion and vascularization of tissues. Recently, a novel approach of data acquisition, namely histogram analysis of different images is a novel diagnostic approach, which can provide more information of tissue heterogeneity. The purpose of this study was to analyze possible associations between DWI, and DCE parameters derived from histogram analysis in patients with HNSCC. Overall, 34 patients, 9 women and 25 men, mean age, 56.7±10.2years, with different HNSCC were involved in the study. DWI was obtained by using of an axial echo planar imaging sequence with b-values of 0 and 800s/mm 2 . Dynamic T1w DCE sequence after intravenous application of contrast medium was performed for estimation of the following perfusion parameters: volume transfer constant (K trans ), volume of the extravascular extracellular leakage space (Ve), and diffusion of contrast medium from the extravascular extracellular leakage space back to the plasma (Kep). Both ADC and perfusion parameters maps were processed offline in DICOM format with custom-made Matlab-based application. Thereafter, polygonal ROIs were manually drawn on the transferred maps on each slice. For every parameter, mean, maximal, minimal, and median values, as well percentiles 10th, 25th, 75th, 90th, kurtosis, skewness, and entropy were estimated. Сorrelation analysis identified multiple statistically significant correlations between the investigated parameters. Ve related parameters correlated well with different ADC values. Especially, percentiles 10 and 75, mode, and median values showed stronger correlations in comparison to other parameters. Thereby, the calculated correlation coefficients ranged from 0.62 to 0.69. Furthermore, K trans related parameters showed multiple slightly to moderate significant correlations with different ADC values. Strongest correlations were identified between ADC P75 and K trans min (p=0.58, P=0.0007), and ADC P75 and K trans P10 (p=0.56, P=0.001). Only four K ep related parameters correlated statistically significant with ADC fractions. Strongest correlation was found between K ep max and ADC mode (p=-0.47, P=0.008). Multiple statistically significant correlations between, DWI and DCE MRI parameters derived from histogram analysis were identified in HNSCC. Copyright © 2017 Elsevier Inc. All rights reserved.

Development of a Combined MR Fingerprinting and Diffusion Examination for Prostate Cancer.

PubMed

Yu, Alice C; Badve, Chaitra; Ponsky, Lee E; Pahwa, Shivani; Dastmalchian, Sara; Rogers, Matthew; Jiang, Yun; Margevicius, Seunghee; Schluchter, Mark; Tabayoyong, William; Abouassaly, Robert; McGivney, Debra; Griswold, Mark A; Gulani, Vikas

2017-06-01

Purpose To develop and evaluate an examination consisting of magnetic resonance (MR) fingerprinting-based T1, T2, and standard apparent diffusion coefficient (ADC) mapping for multiparametric characterization of prostate disease. Materials and Methods This institutional review board-approved, HIPAA-compliant retrospective study of prospectively collected data included 140 patients suspected of having prostate cancer. T1 and T2 mapping was performed with fast imaging with steady-state precession-based MR fingerprinting with ADC mapping. Regions of interest were drawn by two independent readers in peripheral zone lesions and normal-appearing peripheral zone (NPZ) tissue identified on clinical images. T1, T2, and ADC were recorded for each region. Histopathologic correlation was based on systematic transrectal biopsy or cognitively targeted biopsy results, if available. Generalized estimating equations logistic regression was used to assess T1, T2, and ADC in the differentiation of (a) cancer versus NPZ, (b) cancer versus prostatitis, (c) prostatitis versus NPZ, and (d) high- or intermediate-grade tumors versus low-grade tumors. Analysis was performed for all lesions and repeated in a targeted biopsy subset. Discriminating ability was evaluated by using the area under the receiver operating characteristic curve (AUC). Results In this study, 109 lesions were analyzed, including 39 with cognitively targeted sampling. T1, T2, and ADC from cancer (mean, 1628 msec ± 344, 73 msec ± 27, and 0.773 × 10 -3 mm 2 /sec ± 0.331, respectively) were significantly lower than those from NPZ (mean, 2247 msec ± 450, 169 msec ± 61, and 1.711 × 10 -3 mm 2 /sec ± 0.269) (P < .0001 for each) and together produced the best separation between these groups (AUC = 0.99). ADC and T2 together produced the highest AUC of 0.83 for separating high- or intermediate-grade tumors from low-grade cancers. T1, T2, and ADC in prostatitis (mean, 1707 msec ± 377, 79 msec ± 37, and 0.911 × 10 -3 mm 2 /sec ± 0.239) were significantly lower than those in NPZ (P < .0005 for each). Interreader agreement was excellent, with an intraclass correlation coefficient greater than 0.75 for both T1 and T2 measurements. Conclusion This study describes the development of a rapid MR fingerprinting- and diffusion-based examination for quantitative characterization of prostatic tissue. © RSNA, 2017 Online supplemental material is available for this article.

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

WE-FG-202-11: Longitudinal Diffusion MRI for Treatment Assessment of Sarcoma Patients with Pre-Operative Radiation Therapy

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

Yang, Y; Cao, M; Kamrava, M

Purpose: Diffusion weighted MRI (DWI) is a promising imaging technique for early prediction of tumor response to radiation therapy. A recently proposed longitudinal DWI strategy using a Co-60 MRI guided RT system (MRIgRT) may bring functional MRI guided adaptive radiation therapy closer to clinical utility. We report our preliminary results of using this longitudinal DWI approach performed on the MRIgRT system for predicting the response of sarcoma patient to preop RT. Methods: Three sarcoma patients who underwent fractionated IMRT were recruited in this study. For all three patients DWI images were acquired immediately following his/her treatment. For each imaging session,more » ten slices were acquired interleaved with the b values covering the gross tumor volume (GTV). The diffusion images were processed to obtain the ADC maps using standard exponential fitting for each voxel. Regions of interest were drawn in the tumor on the diffusion images based on each patient’s clinical GTV contours. Each patient subsequently underwent surgery and the tumor necrosis score was available from standard pathology. The ADC values for each patient were compared to the necrosis scores to assess the predictive value of our longitudinal DWI for tumor response. Results: Each patient underwent 3 to 5 diffusion MRI scans depending on their treatment length. Patient 1 had a relatively unchanged ADC during the course of RT and a necrosis score of 30% at surgery. For patient 2, the mean ADC values decreased from 1.56 × 10-3 to 1.12 × 10-3 mm2/s and the patient’s necrosis score was less than 10%. Patient 3 had a slight increase in the ADC values from 0.59 × 10-3 to 0.71 × 10-3 mm2/s and patient’s necrosis score was 50%. Conclusion: Based on limited data from 3 patients, our longitudinal changes in tumor ADC assessed using the MRIgRT system correlated well with pathology results.« less

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.

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.

Distinction Between Recurrent Glioma and Radiation Injury Using Magnetic Resonance Spectroscopy in Combination With Diffusion-Weighted Imaging

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

Zeng, Q.-S.; Li, C.-F.; Liu Hong

2007-05-01

Purpose: The aim of this study was to explore the diagnostic effectiveness of magnetic resonance (MR) spectroscopy with diffusion-weighted imaging on the evaluation of the recurrent contrast-enhancing areas at the site of treated gliomas. Methods and Materials: In 55 patients who had new contrast-enhancing lesions in the vicinity of the previously resected and irradiated high-grade gliomas, two-dimensional MR spectroscopy and diffusion-weighted imaging were performed. Spectral data for N-acetylaspartate (NAA), choline (Cho), creatine (Cr), lipid (Lip), and lactate (Lac) were analyzed in conjunction with the apparent diffusion coefficient (ADC) in all patients. Diagnosis of these lesions was assigned by means ofmore » follow-up or histopathology. Results: The Cho/NAA and Cho/Cr ratios were significantly higher in recurrent tumor than in regions of radiation injury (p < 0.01). The ADC value and ADC ratios (ADC of contrast-enhancing lesion to matching structure in the contralateral hemisphere) were significantly higher in radiation injury regions than in recurrent tumor (p < 0.01). With MR spectroscopic data, two variables (Cho/NAA and Cho/Cr ratios) were shown to differentiate recurrent glioma from radiation injury, and 85.5% of total subjects were correctly classified into groups. However, with discriminant analysis of MR spectroscopy imaging plus diffusion-weighted imaging, three variables (Cho/NAA, Cho/Cr, and ADC ratio) were identified and 96.4% of total subjects were correctly classified. There was a significant difference between the diagnostic accuracy of the two discriminant analyses (Chi-square = 3.96, p = 0.046). Conclusion: Using discriminant analysis, this study found that MR spectroscopy in combination with ADC ratio, rather than ADC value, can improve the ability to differentiate recurrent glioma and radiation injury.« less

Family with sequence similarity 83, member B is a predictor of poor prognosis and a potential therapeutic target for lung adenocarcinoma expressing wild-type epidermal growth factor receptor.

PubMed

Yamaura, Takumi; Ezaki, Junji; Okabe, Naoyuki; Takagi, Hironori; Ozaki, Yuki; Inoue, Takuya; Watanabe, Yuzuru; Fukuhara, Mitsuro; Muto, Satoshi; Matsumura, Yuki; Hasegawa, Takeo; Hoshino, Mika; Osugi, Jun; Shio, Yutaka; Waguri, Satoshi; Tamura, Hirosumi; Imai, Jun-Ichi; Ito, Emi; Yanagisawa, Yuka; Honma, Reiko; Watanabe, Shinya; Suzuki, Hiroyuki

2018-02-01

Lung adenocarcinoma (ADC) patients with tumors that harbor no targetable driver gene mutation, such as epidermal growth factor receptor ( EGFR ) gene mutations, have unfavorable prognosis, and thus, novel therapeutic targets are required. Family with sequence similarity 83, member B ( FAM83B ) is a biomarker for squamous cell lung cancer. FAM83B has also recently been shown to serve an important role in the EGFR signaling pathway. In the present study, the molecular and clinical impact of FAM83B in lung ADC was investigated. Matched tumor and adjacent normal tissue samples were obtained from 216 patients who underwent complete lung resection for primary lung ADC and were examined for FAM83B expression using cDNA microarray analysis. The associations between FAM83B expression and clinicopathological parameters, including patient survival, were examined. FAM83B was highly expressed in tumors from males, smokers and in tumors with wild-type EGFR . Multivariate analyses further confirmed that wild-type EGFR tumors were significantly positively associated with FAM83B expression. In survival analysis, FAM83B expression was associated with poor outcomes in disease-free survival and overall survival, particularly when stratified against tumors with wild-type EGFR . Furthermore, FAM83B knockdown was performed to investigate its phenotypic effect on lung ADC cell lines. Gene silencing by FAM83B RNA interference induced growth suppression in the HLC-1 and H1975 lung ADC cell lines. FAM83B may be involved in lung ADC tumor proliferation and can be a predictor of poor survival. FAM83B is also a potential novel therapeutic target for ADC with wild-type EGFR .

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.

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.

39 CFR 121.3 - Standard Mail.

Code of Federal Regulations, 2010 CFR

2010-07-01

... Facility (SCF) turnaround Standard Mail® pieces accepted at origin before the day zero Critical Entry Time... origin before the day zero Critical Entry Time is 4 days when the OPD&C/F and the ADC are the same... intra-Network Distribution Center (NDC) Standard Mail pieces accepted at origin before the day-zero...

39 CFR 121.3 - Standard Mail.

Code of Federal Regulations, 2011 CFR

2011-07-01

... Facility (SCF) turnaround Standard Mail® pieces accepted at origin before the day zero Critical Entry Time... origin before the day zero Critical Entry Time is 4 days when the OPD&C/F and the ADC are the same... intra-Network Distribution Center (NDC) Standard Mail pieces accepted at origin before the day-zero...

The correlation between apparent diffusion coefficient and tumor cellularity in patients: a meta-analysis.

PubMed

Chen, Lihua; Liu, Min; Bao, Jing; Xia, Yunbao; Zhang, Jiuquan; Zhang, Lin; Huang, Xuequan; Wang, Jian

2013-01-01

To perform a meta-analysis exploring the correlation between the apparent diffusion coefficient (ADC) and tumor cellularity in patients. We searched medical and scientific literature databases for studies discussing the correlation between the ADC and tumor cellularity in patients. Only studies that were published in English or Chinese prior to November 2012 were considered for inclusion. Summary correlation coefficient (r) values were extracted from each study, and 95% confidence intervals (CIs) were calculated. Sensitivity and subgroup analyses were performed to investigate potential heterogeneity. Of 189 studies, 28 were included in the meta-analysis, comprising 729 patients. The pooled r for all studies was -0.57 (95% CI: -0.62, -0.52), indicating notable heterogeneity (P<0.001). After the sensitivity analysis, two studies were excluded, and the pooled r was -0.61 (95% CI: -0.66, -0.56) and was not significantly heterogeneous (P = 0.127). Regarding tumor type subgroup analysis, there were sufficient data to support a strong negative correlation between the ADC and cellularity for brain tumors. There was no notable evidence of publication bias. There is a strong negative correlation between the ADC and tumor cellularity in patients, particularly in the brain. However, larger, prospective studies are warranted to validate these findings in other cancer types.

A network collaboration implementing technology to improve medication dispensing and administration in critical access hospitals.

PubMed

Wakefield, Douglas S; Ward, Marcia M; Loes, Jean L; O'Brien, John

2010-01-01

We report how seven independent critical access hospitals collaborated with a rural referral hospital to standardize workflow policies and procedures while jointly implementing the same health information technologies (HITs) to enhance medication care processes. The study hospitals implemented the same electronic health record, computerized provider order entry, pharmacy information systems, automated dispensing cabinets (ADC), and barcode medication administration systems. We conducted interviews and examined project documents to explore factors underlying the successful implementation of ADC and barcode medication administration across the network hospitals. These included a shared culture of collaboration; strategic sequencing of HIT component implementation; interface among HIT components; strategic placement of ADCs; disciplined use and sharing of workflow analyses linked with HIT applications; planning for workflow efficiencies; acquisition of adequate supply of HIT-related devices; and establishing metrics to monitor HIT use and outcomes.

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.

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.

Antibody-drug conjugate targeting CD46 eliminates multiple myeloma cells.

PubMed

Sherbenou, Daniel W; Aftab, Blake T; Su, Yang; Behrens, Christopher R; Wiita, Arun; Logan, Aaron C; Acosta-Alvear, Diego; Hann, Byron C; Walter, Peter; Shuman, Marc A; Wu, Xiaobo; Atkinson, John P; Wolf, Jeffrey L; Martin, Thomas G; Liu, Bin

2016-12-01

Multiple myeloma is incurable by standard approaches because of inevitable relapse and development of treatment resistance in all patients. In our prior work, we identified a panel of macropinocytosing human monoclonal antibodies against CD46, a negative regulator of the innate immune system, and constructed antibody-drug conjugates (ADCs). In this report, we show that an anti-CD46 ADC (CD46-ADC) potently inhibited proliferation in myeloma cell lines with little effect on normal cells. CD46-ADC also potently eliminated myeloma growth in orthometastatic xenograft models. In primary myeloma cells derived from bone marrow aspirates, CD46-ADC induced apoptosis and cell death, but did not affect the viability of nontumor mononuclear cells. It is of clinical interest that the CD46 gene resides on chromosome 1q, which undergoes genomic amplification in the majority of relapsed myeloma patients. We found that the cell surface expression level of CD46 was markedly higher in patient myeloma cells with 1q gain than in those with normal 1q copy number. Thus, genomic amplification of CD46 may serve as a surrogate for target amplification that could allow patient stratification for tailored CD46-targeted therapy. Overall, these findings indicate that CD46 is a promising target for antibody-based treatment of multiple myeloma, especially in patients with gain of chromosome 1q.

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

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.

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.

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.

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.

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

Predicting the nodal status in gastric cancers: The role of apparent diffusion coefficient histogram characteristic analysis.

PubMed

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

2017-10-01

To explore the application of histogram analysis in preoperative T and N staging of gastric cancers, with a focus on characteristic parameters of apparent diffusion coefficient (ADC) maps. Eighty-seven patients with gastric cancers underwent diffusion weighted magnetic resonance imaging (b=0, 1000s/mm 2 ), which generated ADC maps. Whole-volume histogram analysis was performed on ADC maps and 7 characteristic parameters were obtained. All those patients underwent surgery and postoperative pathologic T and N stages were determined. Four parameters, including skew, kurtosis, s-sD av and sample number, showed significant differences among gastric cancers at different T and N stages. Most parameters correlated with T and N stages significantly and worked in differentiating gastric cancers at different T or N stages. Especially skew yielded a sensitivity of 0.758, a specificity of 0.810, and an area under the curve (AUC) of 0.802 for differentiating gastric cancers with and without lymph node metastasis (P<0.001). All the parameters, except AUC low , showed good or excellent inter-observer agreement with intra-class correlation coefficients ranging from 0.710 to 0.991. Characteristic parameters derived from whole-volume ADC histogram analysis could help assessing preoperative T and N stages of gastric cancers. Copyright © 2017. Published by Elsevier Inc.

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

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.

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.

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.

Diffusion tensor eigenvector directional color imaging patterns in the evaluation of cerebral white matter tracts altered by tumor.

PubMed

Field, Aaron S; Alexander, Andrew L; Wu, Yu-Chien; Hasan, Khader M; Witwer, Brian; Badie, Behnam

2004-10-01

To categorize the varied appearances of tumor-altered white matter (WM) tracts on diffusion tensor eigenvector directional color maps. Diffusion tensor imaging (DTI) was obtained preoperatively in 13 patients with brain tumors ranging from benign to high-grade malignant, including primary and metastatic lesions, and maps of apparent diffusion coefficient (ADC), fractional anisotropy (FA), and major eigenvector direction were generated. Regions of interest (ROIs) were drawn within identifiable WM tracts affected by tumor, avoiding grossly cystic and necrotic regions, known fiber crossings, and gray matter. Patterns of WM tract alteration were categorized on the basis of qualitative analysis of directional color maps and correlation analysis of ADC and FA. Four basic patterns of WM alteration were identified: 1) normal or nearly normal FA and ADC, with abnormal tract location or tensor directions attributable to bulk mass displacement, 2) moderately decreased FA and increased ADC with normal tract locations and tensor directions, 3) moderately decreased FA and increased ADC with abnormal tensor directions, and 4) near isotropy. FA and ADC were inversely correlated for Patterns 1-3 but did not discriminate edema from infiltrating tumor. However, in the absence of mass displacement, infiltrating tumor was found to produce tensor directional changes that were not observed with vasogenic edema, suggesting the possibility of discrimination on the basis of directional statistics. Tumor alteration of WM tracts tends to produce one of four patterns on FA and directional color maps. Clinical application of these patterns must await further study. Copyright 2004 Wiley-Liss, Inc.

Pancreatic hardness: Correlation of surgeon’s palpation, durometer measurement and preoperative magnetic resonance imaging features

PubMed Central

Hong, Tae Ho; Choi, Joon-Il; Park, Michael Yong; Rha, Sung Eun; Lee, Young Joon; You, Young Kyoung; Choi, Moon Hyung

2017-01-01

AIM To evaluate the correlation between subjective assessments of pancreatic hardness based on the palpation, objective measurements using a durometer, and magnetic resonance imaging (MRI) findings for assessing pancreatic hardness. METHODS Eighty-three patients undergoing pancreatectomies were enrolled. An experienced surgeon subjectively evaluated the pancreatic hardness in the surgical field by palpation. The pancreatic hardness was also objectively evaluated using a durometer. Preoperative MRI findings were evaluated by a radiologist in terms of the apparent diffusion coefficient (ADC) values, the relative signal intensity decrease (RSID) of the pancreatic parenchyma, and the diameter of the pancreatic parenchyma and duct. Durometer measurement results, ADC values, RSID, pancreatic duct and parenchyma diameters, and the ratio of the diameters of the duct and parenchyma were compared between pancreases judged to be soft or hard pancreas on the palpation. A correlation analysis was also performed between the durometer and MRI measurements. RESULTS The palpation assessment classified 44 patients as having a soft pancreas and 39 patients as having a hard pancreas. ADC values were significantly lower in the hard pancreas group. The ductal diameter and duct-to-pancreas ratio were significantly higher in the hard pancreas group. For durometer measurements, a correlation analysis showed a positive correlation with the ductal diameter and the duct-to-pancreas ratio and a negative correlation with ADC values. CONCLUSION Hard pancreases showed lower ADC values, a wider pancreatic duct diameter and a higher duct-to-pancreas ratio than soft pancreases. Additionally, the ADC values, diameter of the pancreatic duct and duct-to-pancreas ratio were closely correlated with the durometer results. PMID:28373771

Pancreatic hardness: Correlation of surgeon's palpation, durometer measurement and preoperative magnetic resonance imaging features.

PubMed

Hong, Tae Ho; Choi, Joon-Il; Park, Michael Yong; Rha, Sung Eun; Lee, Young Joon; You, Young Kyoung; Choi, Moon Hyung

2017-03-21

To evaluate the correlation between subjective assessments of pancreatic hardness based on the palpation, objective measurements using a durometer, and magnetic resonance imaging (MRI) findings for assessing pancreatic hardness. Eighty-three patients undergoing pancreatectomies were enrolled. An experienced surgeon subjectively evaluated the pancreatic hardness in the surgical field by palpation. The pancreatic hardness was also objectively evaluated using a durometer. Preoperative MRI findings were evaluated by a radiologist in terms of the apparent diffusion coefficient (ADC) values, the relative signal intensity decrease (RSID) of the pancreatic parenchyma, and the diameter of the pancreatic parenchyma and duct. Durometer measurement results, ADC values, RSID, pancreatic duct and parenchyma diameters, and the ratio of the diameters of the duct and parenchyma were compared between pancreases judged to be soft or hard pancreas on the palpation. A correlation analysis was also performed between the durometer and MRI measurements. The palpation assessment classified 44 patients as having a soft pancreas and 39 patients as having a hard pancreas. ADC values were significantly lower in the hard pancreas group. The ductal diameter and duct-to-pancreas ratio were significantly higher in the hard pancreas group. For durometer measurements, a correlation analysis showed a positive correlation with the ductal diameter and the duct-to-pancreas ratio and a negative correlation with ADC values. Hard pancreases showed lower ADC values, a wider pancreatic duct diameter and a higher duct-to-pancreas ratio than soft pancreases. Additionally, the ADC values, diameter of the pancreatic duct and duct-to-pancreas ratio were closely correlated with the durometer results.

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.

Experimental demonstration of a real-time high-throughput digital DC blocker for compensating ADC imperfections in optical fast-OFDM receivers.

PubMed

Zhang, Lu; Ouyang, Xing; Shao, Xiaopeng; Zhao, Jian

2016-06-27

Performance degradation induced by the DC components at the output of real-time analogue-to-digital converter (ADC) is experimentally investigated for optical fast-OFDM receiver. To compensate this degradation, register transfer level (RTL) circuits for real-time digital DC blocker with 20GS/s throughput are proposed and implemented in field programmable gate array (FPGA). The performance of the proposed real-time digital DC blocker is experimentally investigated in a 15Gb/s optical fast-OFDM system with intensity modulation and direct detection over 40 km standard single-mode fibre. The results show that the fixed-point DC blocker has negligible performance penalty compared to the offline floating point one, and can overcome the error floor of the fast OFDM receiver caused by the DC components from the real-time ADC output.

Automatic classification of blank substrate defects

NASA Astrophysics Data System (ADS)

Boettiger, Tom; Buck, Peter; Paninjath, Sankaranarayanan; Pereira, Mark; Ronald, Rob; Rost, Dan; Samir, Bhamidipati

2014-10-01

Mask preparation stages are crucial in mask manufacturing, since this mask is to later act as a template for considerable number of dies on wafer. Defects on the initial blank substrate, and subsequent cleaned and coated substrates, can have a profound impact on the usability of the finished mask. This emphasizes the need for early and accurate identification of blank substrate defects and the risk they pose to the patterned reticle. While Automatic Defect Classification (ADC) is a well-developed technology for inspection and analysis of defects on patterned wafers and masks in the semiconductors industry, ADC for mask blanks is still in the early stages of adoption and development. Calibre ADC is a powerful analysis tool for fast, accurate, consistent and automatic classification of defects on mask blanks. Accurate, automated classification of mask blanks leads to better usability of blanks by enabling defect avoidance technologies during mask writing. Detailed information on blank defects can help to select appropriate job-decks to be written on the mask by defect avoidance tools [1][4][5]. Smart algorithms separate critical defects from the potentially large number of non-critical defects or false defects detected at various stages during mask blank preparation. Mechanisms used by Calibre ADC to identify and characterize defects include defect location and size, signal polarity (dark, bright) in both transmitted and reflected review images, distinguishing defect signals from background noise in defect images. The Calibre ADC engine then uses a decision tree to translate this information into a defect classification code. Using this automated process improves classification accuracy, repeatability and speed, while avoiding the subjectivity of human judgment compared to the alternative of manual defect classification by trained personnel [2]. This paper focuses on the results from the evaluation of Automatic Defect Classification (ADC) product at MP Mask Technology Center (MPMask). The Calibre ADC tool was qualified on production mask blanks against the manual classification. The classification accuracy of ADC is greater than 95% for critical defects with an overall accuracy of 90%. The sensitivity to weak defect signals and locating the defect in the images is a challenge we are resolving. The performance of the tool has been demonstrated on multiple mask types and is ready for deployment in full volume mask manufacturing production flow. Implementation of Calibre ADC is estimated to reduce the misclassification of critical defects by 60-80%.

Clinically insignificant prostate cancer suitable for active surveillance according to Prostate Cancer Research International: Active surveillance criteria: Utility of PI-RADS v2.

PubMed

Yim, Jae Hyun; Kim, Chan Kyo; Kim, Jae-Hun

2018-04-01

Active surveillance (AS) is an important treatment strategy for prostate cancer (PCa). Prostate Imaging-Reporting and Data System (PI-RADS) v2 has been addressed, but few studies have reported the value of PI-RADS v2 for assessing risk stratification in patients with PCa, especially on selecting potential candidates for AS. To investigate the utility of PI-RADS v2 and apparent diffusion coefficient (ADC) in evaluating patients with insignificant PCa, who are suitable for AS. Retrospective. In all, 238 patients with PCa who met the Prostate Cancer Research International: Active Surveillance criteria underwent radical prostatectomy. 3.0T, including T 2 -weighted, diffusion-weighted, and dynamic contrast-enhanced imaging. Insignificant cancer was defined histopathologically as an organ-confined disease with a tumor volume <0.5 cm 3 without Gleason score 4-5. Patients were divided into two groups based on the PI-RADS v2 and tumor ADC: A, PI-RADS score ≤3 and ADC ≥1.095 × 10 -3 mm 2 /s; and B, PI-RADS score 4-5 or ADC <1.095 × 10 -3 mm 2 /s. Preoperative clinical and imaging variables were evaluated regarding the associations with insignificant cancer. Of the 238 patients, 101 (42.8%) were diagnosed with insignificant cancer on pathological findings. The number of positive cores, prostate-specific antigen density (PSAD), PI-RADS v2 and tumor ADC were significantly associated with insignificant cancer on univariate analysis (P < 0.05). However, multivariate analysis indicated tumor ADC (odds ratio [OR] = 4.57, P < 0.001) and PI-RADS v2 (OR = 3.60, P < 0.001) were independent predictors of insignificant cancer. Area under the receiver operating characteristics curve (AUC) reached 0.803 when PI-RADS v2 (AUC = 0.747) was combined with tumor ADC (AUC = 0.786). The PI-RADS v2 together with tumor ADC may be a useful marker for predicting patients with insignificant PCa when considering AS. 4 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;47:1072-1079. © 2017 International Society for Magnetic Resonance in Medicine.

Whole-tumor MRI histogram analyses of hepatocellular carcinoma: Correlations with Ki-67 labeling index.

PubMed

Hu, Xin-Xing; Yang, Zhao-Xia; Liang, He-Yue; Ding, Ying; Grimm, Robert; Fu, Cai-Xia; Liu, Hui; Yan, Xu; Ji, Yuan; Zeng, Meng-Su; Rao, Sheng-Xiang

2017-08-01

To evaluate whether whole-tumor histogram-derived parameters for an apparent diffusion coefficient (ADC) map and contrast-enhanced magnetic resonance imaging (MRI) could aid in assessing Ki-67 labeling index (LI) of hepatocellular carcinoma (HCC). In all, 57 patients with HCC who underwent pretreatment MRI with a 3T MR scanner were included retrospectively. Histogram parameters including mean, median, standard deviation, skewness, kurtosis, and percentiles (5 th , 25 th , 75 th , 95 th ) were derived from the ADC map and MR enhancement. Correlations between histogram parameters and Ki-67 LI were evaluated and differences between low Ki-67 (≤10%) and high Ki-67 (>10%) groups were assessed. Mean, median, 5 th , 25 th , 75 th percentiles of ADC, and mean, median, 25 th , 75 th , 95 th percentiles of enhancement of arterial phase (AP) demonstrated significant inverse correlations with Ki-67 LI (rho up to -0.48 for ADC, -0.43 for AP) and showed significant differences between low and high Ki-67 groups (P < 0.001-0.04). Areas under the receiver operator characteristics (ROC) curve for identification of high Ki-67 were 0.78, 0.77, 0.79, 0.82, and 0.76 for mean, median, 5 th , 25 th , 75 th percentiles of ADC, respectively, and 0.74, 0.81, 0.76, 0.82, 0.69 for mean, median, 25 th , 75 th , 95 th percentiles of AP, respectively. Histogram-derived parameters of ADC and AP were potentially helpful for predicting Ki-67 LI of HCC. 3 Technical Efficacy: Stage 3 J. MAGN. RESON. IMAGING 2017;46:383-392. © 2016 International Society for Magnetic Resonance in Medicine.

Clinical utility of apparent diffusion coefficient values obtained using high b-value when diagnosing prostate cancer using 3 tesla MRI: comparison between ultra-high b-value (2000 s/mm²) and standard high b-value (1000 s/mm²).

PubMed

Kitajima, Kazuhiro; Takahashi, Satoru; Ueno, Yoshiko; Yoshikawa, Takeshi; Ohno, Yoshiharu; Obara, Makoto; Miyake, Hideaki; Fujisawa, Masato; Sugimura, Kazuro

2012-07-01

To determine whether the apparent diffusion coefficient (ADC) obtained using b = 2000 s/mm(2) upon 3 Tesla (T) diffusion-weighted MRI is superior to b = 1000 s/mm(2) for discriminating malignant from normal prostate tissue and predicting the aggressiveness of prostate cancer, using histopathological findings of radical prostatectomy as a reference. Eighty prostate cancer patients underwent preoperative 3T MRI including diffusion weighted imaging with b-values of 0, 1000, and 2000 s/mm(2) . ADCs were measured for malignant lesions and normal sites on three sets of ADC maps calculated with monoexponential fitting between b = 0 and 1000, 0 and 2000, and 1000 and 2000, respectively. The relationship between the ADC and Gleason score was evaluated. The areas under the ROC curves for b = 0,1000, b = 0,2000, and b = 1000,2000 were 0.896, 0.937, and 0.857, respectively, in the peripheral zone (PZ) and 0.877, 0.889, and 0.731, respectively, in the transition zone (TZ). The difference between b = 0,1000 and b = 0,2000 was significant in PZ (P = 0.033), but not in TZ (P = 0.84). Weak but significant negative correlations were identified between ADCs and Gleason score in both PZ and TZ cancer at b = 0,1000 and b = 0,2000 (r = -0.323 to -0.341). For 3T MRI, ADCs using b = 0,2000 are more accurate than b = 0,1000 for diagnosing PZ cancer, and as accurate for TZ cancer. Copyright © 2012 Wiley Periodicals, Inc.

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.

A 10 GS/s time-interleaved ADC in 0.25 micrometer CMOS technology

NASA Astrophysics Data System (ADS)

Aytar, Oktay; Tangel, Ali; Afacan, Engin

2017-11-01

This paper presents design and simulation of a 4-bit 10 GS/s time interleaved ADC in 0.25 micrometer CMOS technology. The designed TI-ADC has 4 channels including 4-bit flash ADC in each channel, in which area and power efficiency are targeted. Therefore, basic standard cell logic gates are preferred. Meanwhile, the aspect ratios in the gate designs are kept as small as possible considering the speed performance. In the literature, design details of the timing control circuits have not been provided, whereas the proposed timing control process is comprehensively explained and design details of the proposed timing control process are clearly presented in this study. The proposed circuits producing consecutive pulses for timing control of the input S/H switches (ie the analog demultiplexer front-end circuitry) and the very fast digital multiplexer unit at the output are the main contributions of this study. The simulation results include +0.26/-0.22 LSB of DNL and +0.01/-0.44 LSB of INL, layout area of 0.27 mm2, and power consumption of 270 mW. The provided power consumption, DNL and INL measures are observed at 100 MHz input with 10 GS/s sampling rate.

Accurate estimation of camera shot noise in the real-time

NASA Astrophysics Data System (ADS)

Cheremkhin, Pavel A.; Evtikhiev, Nikolay N.; Krasnov, Vitaly V.; Rodin, Vladislav G.; Starikov, Rostislav S.

2017-10-01

Nowadays digital cameras are essential parts of various technological processes and daily tasks. They are widely used in optics and photonics, astronomy, biology and other various fields of science and technology such as control systems and video-surveillance monitoring. One of the main information limitations of photo- and videocameras are noises of photosensor pixels. Camera's photosensor noise can be divided into random and pattern components. Temporal noise includes random noise component while spatial noise includes pattern noise component. Temporal noise can be divided into signal-dependent shot noise and signal-nondependent dark temporal noise. For measurement of camera noise characteristics, the most widely used methods are standards (for example, EMVA Standard 1288). It allows precise shot and dark temporal noise measurement but difficult in implementation and time-consuming. Earlier we proposed method for measurement of temporal noise of photo- and videocameras. It is based on the automatic segmentation of nonuniform targets (ASNT). Only two frames are sufficient for noise measurement with the modified method. In this paper, we registered frames and estimated shot and dark temporal noises of cameras consistently in the real-time. The modified ASNT method is used. Estimation was performed for the cameras: consumer photocamera Canon EOS 400D (CMOS, 10.1 MP, 12 bit ADC), scientific camera MegaPlus II ES11000 (CCD, 10.7 MP, 12 bit ADC), industrial camera PixeLink PL-B781F (CMOS, 6.6 MP, 10 bit ADC) and video-surveillance camera Watec LCL-902C (CCD, 0.47 MP, external 8 bit ADC). Experimental dependencies of temporal noise on signal value are in good agreement with fitted curves based on a Poisson distribution excluding areas near saturation. Time of registering and processing of frames used for temporal noise estimation was measured. Using standard computer, frames were registered and processed during a fraction of second to several seconds only. Also the accuracy of the obtained temporal noise values was estimated.

Use of diffusion-weighted magnetic resonance imaging to distinguish between lung cancer and focal inflammatory lesions: a comparison of intravoxel incoherent motion derived parameters and apparent diffusion coefficient.

PubMed

Deng, Yu; Li, Xinchun; Lei, Yongxia; Liang, Changhong; Liu, Zaiyi

2016-11-01

Background Using imaging techniques to diagnose malignant and inflammatory lesions in the lung can be challenging. Purpose To compare intravoxel incoherent motion (IVIM) and apparent diffusion coefficient (ADC) magnetic resonance imaging (MRI) analysis in their ability to discriminate lung cancer from focal inflammatory lung lesions. Material and Methods Thirty-eight patients with lung masses were included: 30 lung cancers and eight inflammatory lesions. Patients were imaged with 3.0T MRI diffusion weighted imaging (DWI) using 10 b values (range, 0-1000 s/mm 2 ). Tissue diffusivity ( D), pseudo-diffusion coefficient ( D*), and perfusion fraction ( f) were calculated using segmented biexponential analysis. ADC (total) was calculated with monoexponential fitting of the DWI data. D, D*, f, and ADC were compared between lung cancer and inflammatory lung lesions. Receiver operating characteristic analysis was performed for all DWI parameters. Results The ADC was significantly higher for inflammatory lesions than for lung cancer ([1.21 ± 0.20] × 10 -3 mm 2 /s vs. [0.97 ± 0.15] × 10 -3 mm 2 /s; P = 0.004). By IVIM, f was found to be significantly higher in inflammatory lesions than lung cancer ([46.10 ± 12.92] % vs. [29.29 ± 10.89] %; P = 0.005). There was no difference in D and D* between lung cancer and inflammatory lesions ( P = 0.747 and 0.124, respectively). f showed comparable diagnostic performance with ADC in differentiating lung cancer from inflammatory lung lesions, with areas under the curve of 0.833 and 0.826, sensitivity 80.0% and 73.3%, and specificity 75.0% and 87.5%, respectively. Conclusion The IVIM parameter f value provides comparable diagnostic performance with ADC and could be used as a surrogate marker for differentiating lung cancer from inflammatory lesions.

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.

DW MRI at 3.0 T versus FDG PET/CT for detection of malignant pulmonary tumors.

PubMed

Zhang, Jian; Cui, Long-Biao; Tang, Xing; Ren, Xin-Ling; Shi, Jie-Ran; Yang, Hai-Nan; Zhang, Yan; Li, Zhi-Kui; Wu, Chang-Gui; Jian, Wen; Zhao, Feng; Ti, Xin-Yu; Yin, Hong

2014-02-01

Emerging evidence suggests that diffusion-weighted magnetic resonance imaging (DW MRI) could be useful for tumor detection with N and M staging of lung cancer in place of fluorine 18 fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT). DW MRI at 3.0 T and FDG PET/CT were performed before therapy in 113 patients with pulmonary nodules. Mean apparent diffusion coefficient (ADC), maximal standardized uptake value (SUVmax ) and Ki-67 scores were assessed. Quantitatively, specificity and accuracy of ADC (91.7 and 92.9%, respectively) were significantly higher than those of SUVmax (66.7 and 77.9% respectively, p < 0.05), although sensitivity was not significantly different between them (93.5 and 83.1%, p > 0.05). Qualitatively, sensitivity, specificity and accuracy of DW MRI (96.1, 83.3 and 92.0%, respectively) were also not significantly different from that of FDG PET/CT (88.3, 83.3 and 86.7%, respectively, p > 0.05). Significant negative correlation was found between Ki-67 score and ADC (r = -0.66, p < 0.05), ADC and SUVmax (r = -0.37, p < 0.05), but not between Ki-67 score and SUVmax (r = -0.11, p > 0.05). In conclusion, quantitative and qualitative assessments for detection of malignant pulmonary tumors with DW MRI at 3.0 T are superior to those with FDG PET/CT. Furthermore, ADC could predict the malignancy of lung cancer. © 2013 UICC.

A 10 bit 200 MS/s pipeline ADC using loading-balanced architecture in 0.18 μm CMOS

NASA Astrophysics Data System (ADS)

Wang, Linfeng; Meng, Qiao; Zhi, Hao; Li, Fei

2017-07-01

A new loading-balanced architecture for high speed and low power consumption pipeline analog-to-digital converter (ADC) is presented in this paper. The proposed ADC uses SHA-less, op-amp and capacitor-sharing technique, capacitor-scaling scheme to reduce the die area and power consumption. A new capacitor-sharing scheme was proposed to cancel the extra reset phase of the feedback capacitors. The non-standard inter-stage gain increases the feedback factor of the first stage and makes it equal to the second stage, by which, the load capacitor of op-amp shared by the first and second stages is balanced. As for the fourth stage, the capacitor and op-amp no longer scale down. From the system’s point of view, all load capacitors of the shared OTAs are balanced by employing a loading-balanced architecture. The die area and power consumption are optimized maximally. The ADC is implemented in a 0.18 μm 1P6M CMOS technology, and occupies a die area of 1.2 × 1.2 mm{}2. The measurement results show a 55.58 dB signal-to-noise-and-distortion ratio (SNDR) and 62.97 dB spurious-free dynamic range (SFDR) with a 25 MHz input operating at a 200 MS/s sampling rate. The proposed ADC consumes 115 mW at 200 MS/s from a 1.8 V supply.

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.

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.

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.

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.

Rivastigmine transdermal patch and capsule in Alzheimer's disease: influence of disease stage on response to therapy.

PubMed

Farlow, Martin R; Grossberg, George T; Meng, Xiangyi; Olin, Jason; Somogyi, Monique

2011-12-01

The cholinesterase inhibitor rivastigmine is approved for the symptomatic treatment of mild to moderate Alzheimer's disease (AD). This exploratory, hypothesis-forming analysis assessed response to rivastigmine according to severity of dementia at baseline. This was a retrospective analysis of a large randomized, placebo-controlled trial (ENA713D2320). AD patients treated with 9.5 mg/24 h rivastigmine patch, 17.4 mg/24 h rivastigmine patch, rivastigmine capsule (12 mg/day), or placebo were stratified according to baseline Mini-Mental State Examination (MMSE) scores: ≥7 to ≤12 (severe disease), ≥13 to ≤15 (moderately severe), ≥16 to ≤18 (moderate), or ≥19 to ≤25 (mild to moderate). Changes from baseline at Week 24 on Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog), Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC), and Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) were assessed. Based on baseline MMSE scores, 141, 228, 333, and 348 patients had severe, moderately severe, moderate, and mild to moderate dementia. Worsening of ADAS-cog, ADCS-CGIC, and ADCS-ADL scores in patients receiving placebo were greater in patients with more severe dementia. Significant improvements versus placebo were seen with rivastigmine patch and/or capsule on ADAS-cog, ADCS-CGIC, and ADCS-ADL scores in patients with severe, moderately severe, and moderate AD (all p < 0.05). However, no significant improvements were seen in rivastigmine-treated patients with mild to moderate AD. Rivastigmine benefits AD patients across dementia stages. Similar to previous cholinesterase inhibitor studies, greatest treatment effects with rivastigmine patch and capsule were seen in patients with more advanced dementia, most likely driven by greater placebo decline in this population. Copyright © 2010 John Wiley & Sons, Ltd.

Lung Adenocarcinoma With MUC4 Expression Is Associated With Smoking Status, HER2 Protein Expression, and Poor Prognosis: Clinicopathologic Analysis of 338 Cases.

PubMed

Rokutan-Kurata, Mariyo; Yoshizawa, Akihiko; Sumiyoshi, Shinji; Sonobe, Makoto; Menju, Toshi; Momose, Masanobu; Koyama, Mizuki; Shigeto, Shohei; Fujimoto, Masakazu; Zhang, Meng; Morita, Satoshi; Date, Hiroshi; Haga, Hironori

2017-07-01

MUC4 is a transmembrane glycoprotein that plays a role in the cell growth signaling pathway and has been studied in various organ malignancies. This study aimed to analyze MUC4 expression in resected lung adenocarcinomas (ADCs) to define the clinicopathologic characteristics of MUC4-positive cancers. Immunohistochemical MUC4 analysis was performed using tissue microarray slides containing 338 lung ADCs. Associations between MUC4 expression and the following clinicopathologic parameters were evaluated: sex; age; smoking status; tumor stage; tumor grade; lymphovascular invasion; pleural invasion; TTF-1 and HNF4α expression; EGFR, KRAS, BRAF, and HER2 mutation status; and ALK and ROS1 fusion status. Ninety-four tumors (27.8%) were MUC4 positive. Most patients with MUC4-positive tumors were male (P < .001) and smokers (P = .006). Moreover, MUC4 expression was significantly associated with solid ADCs (P < .001) and vascular invasion (P = .001). MUC4 expression inversely correlated with TTF-1 expression (P = .020) and EGFR mutations (P = .004). Interestingly, MUC4 expression correlated with HER2 protein expression (P = .042), although MUC4 expression did not correlate with HER2 DNA amplification or HER2 gene mutations. Patients with MUC4-positive tumors had significantly worse prognoses compared to patients with MUC4-negative tumors (P = .025). The present study showed that MUC4-positive lung ADCs correlated with male smokers, solid ADCs, negative TTF-1 expression, the EGFR wild-type gene, HER2 protein expression, and poorer prognoses. These results suggest that MUC4-positive lung ADC may be a distinct subtype found in patients with smoking-related poor outcomes, mediated by HER2 signaling pathway. Copyright © 2016 Elsevier Inc. All rights reserved.

Conventional vs. reduced field of view diffusion weighted imaging of the prostate: Comparison of image quality, correlation with histology, and inter-reader agreement.

PubMed

Warndahl, Brent A; Borisch, Eric A; Kawashima, Akira; Riederer, Stephen J; Froemming, Adam T

2018-04-01

To evaluate if Field of view Optimized and Constrained Undistorted Single shot (FOCUS) (GE Healthcare, Waukesha, WI) diffusion weighted images (DWI) provide more reliable imaging than conventional DWI, with non-inferior quantitative apparent diffusion coefficient (ADC) results. IRB approval was obtained for this study of 43 patients (44 exams, one patient with two visits) that underwent multiparametric prostate MRI with two DWI sequences and subsequent radical prostatectomy with histology as the gold standard. Randomized DWI sequence images were graded independently by two blinded experienced prostate MRI radiologists with a period of memory extinction between the two separate reading sessions. Blinded images were also reviewed head to head in a later session for direct comparison. Multiple parameters were measured from a region of interest in a dominant lesion as well as two control areas. Patient characteristics were collected by chart review. There was good correlation between the mean ADC value for lesions obtained by conventional and FOCUS DWI (ρ=0.85), with no trend toward any systematic difference, and equivalent correlation between ADC measurements and Gleason score. Agreement between the two readers was significantly higher for lesion ROI analysis with the FOCUS DWI derived ADC values (CCC 0.839) compared with the conventional ADC values (CCC 0.618; difference 0.221, 95% CI 0.01-0.46). FOCUS showed significantly better image quality scores (separate review: mean 2.17±0.6, p<0.001) compared to the conventional sequence (mean 2.65±0.6, p<0.001). In 13 cases the image quality was improved from grade of 3+ with conventional DWI to <3 with FOCUS DWI, a clinically meaningful improvement. Head-to-head blinded review found 61 ratings showed strong to slight preference for FOCUS, 13 no preference, and 14 slight preference for the conventional sequence. There was also a strong and equivalent correlation between both sequences and PIRADS version 2 grading (ρ=-0.56 and -0.58 for FOCUS and conventional, respectively, p<0.001 for both). FOCUS DWI of the prostate shows significant improvement in inter-reader agreement and image quality. As opposed to previous conflicting smaller studies, we found equivalent ADC metrics compared with the conventional DWI sequence, and preserved correlation with Gleason score. In 52% of patients the improved image quality with FOCUS had the potential to salvage exams with otherwise limited to non-diagnostic DWI. Copyright © 2017 Elsevier Inc. All rights reserved.

Utility of the k-means clustering algorithm in differentiating apparent diffusion coefficient values of benign and malignant neck pathologies.

PubMed

Srinivasan, A; Galbán, C J; Johnson, T D; Chenevert, T L; Ross, B D; Mukherji, S K

2010-04-01

Does the K-means algorithm do a better job of differentiating benign and malignant neck pathologies compared to only mean ADC? The objective of our study was to analyze the differences between ADC partitions to evaluate whether the K-means technique can be of additional benefit to whole-lesion mean ADC alone in distinguishing benign and malignant neck pathologies. MR imaging studies of 10 benign and 10 malignant proved neck pathologies were postprocessed on a PC by using in-house software developed in Matlab. Two neuroradiologists manually contoured the lesions, with the ADC values within each lesion clustered into 2 (low, ADC-ADC(L); high, ADC-ADC(H)) and 3 partitions (ADC(L); intermediate, ADC-ADC(I); ADC(H)) by using the K-means clustering algorithm. An unpaired 2-tailed Student t test was performed for all metrics to determine statistical differences in the means of the benign and malignant pathologies. A statistically significant difference between the mean ADC(L) clusters in benign and malignant pathologies was seen in the 3-cluster models of both readers (P = .03 and .022, respectively) and the 2-cluster model of reader 2 (P = .04), with the other metrics (ADC(H), ADC(I); whole-lesion mean ADC) not revealing any significant differences. ROC curves demonstrated the quantitative differences in mean ADC(H) and ADC(L) in both the 2- and 3-cluster models to be predictive of malignancy (2 clusters: P = .008, area under curve = 0.850; 3 clusters: P = .01, area under curve = 0.825). The K-means clustering algorithm that generates partitions of large datasets may provide a better characterization of neck pathologies and may be of additional benefit in distinguishing benign and malignant neck pathologies compared with whole-lesion mean ADC alone.

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.

Motion corrected DWI with integrated T2-mapping for simultaneous estimation of ADC, T2-relaxation and perfusion in prostate cancer.

PubMed

Skorpil, M; Brynolfsson, P; Engström, M

2017-06-01

Multiparametric magnetic resonance imaging (MRI) and PI-RADS (Prostate Imaging - Reporting and Data System) has become the standard to determine a probability score for a lesion being a clinically significant prostate cancer. T2-weighted and diffusion-weighted imaging (DWI) are essential in PI-RADS, depending partly on visual assessment of signal intensity, while dynamic-contrast enhanced imaging is less important. To decrease inter-rater variability and further standardize image evaluation, complementary objective measures are in need. We here demonstrate a sequence enabling simultaneous quantification of apparent diffusion coefficient (ADC) and T2-relaxation, as well as calculation of the perfusion fraction f from low b-value intravoxel incoherent motion data. Expandable wait pulses were added to a FOCUS DW SE-EPI sequence, allowing the effective echo time to change at run time. To calculate both ADC and f, b-values 200s/mm 2 and 600s/mm 2 were chosen, and for T2-estimation 6 echo times between 64.9ms and 114.9ms were used. Three patients with prostate cancer were examined and all had significantly decreased ADC and T2-values, while f was significantly increased in 2 of 3 tumors. T2 maps obtained in phantom measurements and in a healthy volunteer were compared to T2 maps from a SE sequence with consecutive scans, showing good agreement. In addition, a motion correction procedure was implemented to reduce the effects of prostate motion, which improved T2-estimation. This sequence could potentially enable more objective tumor grading, and decrease the inter-rater variability in the PI-RADS classification. Copyright © 2017 Elsevier Inc. All rights reserved.

Diffusion weighted imaging for the differentiation of breast tumors: From apparent diffusion coefficient to high order diffusion tensor imaging.

PubMed

Teruel, Jose R; Goa, Pål E; Sjøbakk, Torill E; Østlie, Agnes; Fjøsne, Hans E; Bathen, Tone F

2016-05-01

To compare "standard" diffusion weighted imaging, and diffusion tensor imaging (DTI) of 2(nd) and 4(th) -order for the differentiation of malignant and benign breast lesions. Seventy-one patients were imaged at 3 Tesla with a 16-channel breast coil. A diffusion weighted MRI sequence including b = 0 and b = 700 in 30 directions was obtained for all patients. The image data were fitted to three different diffusion models: isotropic model - apparent diffusion coefficient (ADC), 2(nd) -order tensor model (the standard model used for DTI) and a 4(th) -order tensor model, with increased degrees of freedom to describe anisotropy. The ability of the fitted parameters in the different models to differentiate between malignant and benign tumors was analyzed. Seventy-two breast lesions were analyzed, out of which 38 corresponded to malignant and 34 to benign tumors. ADC (using any model) presented the highest discriminative ability of malignant from benign tumors with a receiver operating characteristic area under the curve (AUC) of 0.968, and sensitivity and specificity of 94.1% and 94.7% respectively for a 1.33 × 10(-3) mm(2) /s cutoff. Anisotropy measurements presented high statistical significance between malignant and benign tumors (P < 0.001), but with lower discriminative ability of malignant from benign tumors than ADC (AUC of 0.896 and 0.897 for fractional anisotropy and generalized anisotropy respectively). Statistical significant difference was found between generalized anisotropy and fractional anisotropy for cancers (P < 0.001) but not for benign lesions (P = 0.87). While anisotropy parameters have the potential to provide additional value for breast applications as demonstrated in this study, ADC exhibited the highest differentiation power between malignant and benign breast tumors. © 2015 Wiley Periodicals, Inc.

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

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.

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

Quantitative bioanalysis of antibody-conjugated payload in monkey plasma using a hybrid immuno-capture LC-MS/MS approach: Assay development, validation, and a case study.

PubMed

Liu, Ang; Kozhich, Alexander; Passmore, David; Gu, Huidong; Wong, Richard; Zambito, Frank; Rangan, Vangipuram S; Myler, Heather; Aubry, Anne-Françoise; Arnold, Mark E; Wang, Jian

2015-10-01

Antibody drug conjugates (ADCs) are complex molecules composed of two pharmacologically distinct components, the cytotoxic payload and the antibody. The measurement of the payload molecules that are attached to the antibody in vivo is important for the evaluation of the safety and efficacy of ADCs, and can also provide distinct information compared to the antibody-related analytes. However, analyzing the antibody-conjugated payload is challenging and in some cases may not be feasible. The in vivo change in drug antibody ratio (DAR), due to deconjugation, biotransformation or other clearance phenomena, generates unique and additional challenges for ADC analysis in biological samples. Here, we report a novel hybrid approach with immuno-capture of the ADC, payload cleavage by specific enzyme, and LC-MS/MS of the cleaved payload to quantitatively measure the concentration of payload molecules still attached to the antibody via linker in plasma. The ADC reference material used for the calibration curve is not likely to be identical to the ADC measured in study samples due to the change in DAR distribution over the PK time course. The assay clearly demonstrated that there was no bias in the measurement of antibody-conjugated payload for ADC with varying DAR, which thus allowed accurate quantification even when the DAR distribution dynamically changes in vivo. This hybrid assay was fully validated based on a combination of requirements for both chromatographic and ligand binding methods, and was successfully applied to support a GLP safety study in monkeys. Copyright © 2015 Elsevier B.V. All rights reserved.

Identification of suitable genes contributes to lung adenocarcinoma clustering by multiple meta-analysis methods.

PubMed

Yang, Ze-Hui; Zheng, Rui; Gao, Yuan; Zhang, Qiang

2016-09-01

With the widespread application of high-throughput technology, numerous meta-analysis methods have been proposed for differential expression profiling across multiple studies. We identified the suitable differentially expressed (DE) genes that contributed to lung adenocarcinoma (ADC) clustering based on seven popular multiple meta-analysis methods. Seven microarray expression profiles of ADC and normal controls were extracted from the ArrayExpress database. The Bioconductor was used to perform the data preliminary preprocessing. Then, DE genes across multiple studies were identified. Hierarchical clustering was applied to compare the classification performance for microarray data samples. The classification efficiency was compared based on accuracy, sensitivity and specificity. Across seven datasets, 573 ADC cases and 222 normal controls were collected. After filtering out unexpressed and noninformative genes, 3688 genes were remained for further analysis. The classification efficiency analysis showed that DE genes identified by sum of ranks method separated ADC from normal controls with the best accuracy, sensitivity and specificity of 0.953, 0.969 and 0.932, respectively. The gene set with the highest classification accuracy mainly participated in the regulation of response to external stimulus (P = 7.97E-04), cyclic nucleotide-mediated signaling (P = 0.01), regulation of cell morphogenesis (P = 0.01) and regulation of cell proliferation (P = 0.01). Evaluation of DE genes identified by different meta-analysis methods in classification efficiency provided a new perspective to the choice of the suitable method in a given application. Varying meta-analysis methods always present varying abilities, so synthetic consideration should be taken when providing meta-analysis methods for particular research. © 2015 John Wiley & Sons Ltd.

Geometric distortion correction in prostate diffusion-weighted MRI and its effect on quantitative apparent diffusion coefficient analysis.

PubMed

Nketiah, Gabriel; Selnaes, Kirsten M; Sandsmark, Elise; Teruel, Jose R; Krüger-Stokke, Brage; Bertilsson, Helena; Bathen, Tone F; Elschot, Mattijs

2018-05-01

To evaluate the effect of correction for B 0 inhomogeneity-induced geometric distortion in echo-planar diffusion-weighted imaging on quantitative apparent diffusion coefficient (ADC) analysis in multiparametric prostate MRI. Geometric distortion correction was performed in echo-planar diffusion-weighted images (b = 0, 50, 400, 800 s/mm 2 ) of 28 patients, using two b 0 scans with opposing phase-encoding polarities. Histology-matched tumor and healthy tissue volumes of interest delineated on T 2 -weighted images were mapped to the nondistortion-corrected and distortion-corrected data sets by resampling with and without spatial coregistration. The ADC values were calculated on the volume and voxel level. The effect of distortion correction on ADC quantification and tissue classification was evaluated using linear-mixed models and logistic regression, respectively. Without coregistration, the absolute differences in tumor ADC (range: 0.0002-0.189 mm 2 /s×10 -3 (volume level); 0.014-0.493 mm 2 /s×10 -3 (voxel level)) between the nondistortion-corrected and distortion-corrected were significantly associated (P < 0.05) with distortion distance (mean: 1.4 ± 1.3 mm; range: 0.3-5.3 mm). No significant associations were found upon coregistration; however, in patients with high rectal gas residue, distortion correction resulted in improved spatial representation and significantly better classification of healthy versus tumor voxels (P < 0.05). Geometric distortion correction in DWI could improve quantitative ADC analysis in multiparametric prostate MRI. Magn Reson Med 79:2524-2532, 2018. © 2017 International Society for Magnetic Resonance in Medicine. © 2017 International Society for Magnetic Resonance in Medicine.

[Characteristics of high resolution diffusion weighted imaging apparent diffusion coefficient histogram and its correlations with cancer stages in patients with nasopharyngeal carcinoma].

PubMed

Wang, G J; Wang, Y; Ye, Y; Chen, F; Lu, Y T; Li, S L

2017-11-07

Objective: To investigate the features of apparent diffusion coefficient (ADC) histogram parameters based on entire tumor volume data in high resolution diffusion weighted imaging of nasopharyngeal carcinoma (NPC) and to evaluate its correlations with cancer stages. Methods: This retrospective study included 154 cases of NPC patients[102 males and 52 females, mean age (48±11) years]who had received readout segmentation of long variable echo trains of MRI scan before radiation therapy. The area of tumor was delineated on each section of axial ADC maps to generate ADC histogram by using Image J. ADC histogram of entire tumor along with the histogram parameters-the tumor voxels, ADC(mean), ADC(25%), ADC(50%), ADC(75%), skewness and kurtosis were obtained by merging all sections with SPSS 22.0 software. Intra-observer repeatability was assessed by using intra-class correlation coefficients (ICC). The patients were subdivided into two groups according to cancer volume: small cancer group (<305 voxels, about 2 cm(3)) and large cancer group (≥2 cm(3)). The correlation between ADC histogram parameters and cancer stages was evaluated with Spearman test. Results: The ICC of measuring ADC histogram parameters of tumor voxels, ADC(mean), ADC(25%), ADC(50%), ADC(75%), skewness, kurtosis was 0.938, 0.861, 0.885, 0.838, 0.836, 0.358 and 0.456, respectively. The tumor voxels was positively correlated with T staging ( r =0.368, P <0.05). There were significant differences in tumor voxels among patients with different T stages ( K =22.306, P <0.05). There were significant differences in the ADC(mean), ADC(25%), ADC(50%) among patients with different T stages in the small cancer group( K =8.409, 8.187, 8.699, all P <0.05), and the up-mentioned three indices were positively correlated with T staging ( r =0.221, 0.209, 0.235, all P <0.05). Skewness and kurtosis differed significantly between the groups with different cancer volume( t =-2.987, Z =-3.770, both P <0.05). Conclusion: The tumor volume, tissue uniformity of NPC are important factors affecting ADC and cancer stages, parameters of ADC histogram (ADC(mean), ADC(25%), ADC(50%)) increases with T staging in NPC smaller than 2 cm(3).

Dual-isotope Cryo-imaging Quantitative Autoradiography (CIQA): Anvestigating Antibody-Drug Conjugate Distribution And Payload Delivery Through Imaging.

PubMed

Ilovich, Ohad; Qutaish, Mohammed; Hesterman, Jacob; Orcutt, Kelly; Hoppin, Jack; Polyak, Ildiko; Seaman, Marc; Abu-Yousif, Adnan; Cvet, Donna; Bradley, Daniel

2018-05-04

In vitro properties of antibody drug conjugates (ADCs) such as binding, internalization, and cytotoxicity are often well characterized prior to in vivo studies. Interpretation of in vivo studies could significantly be enhanced by molecular imaging tools. We present here a dual-isotope cryo-imaging quantitative autoradiography (CIQA) methodology combined with advanced 3D imaging and analysis allowing for the simultaneous study of both antibody and payload distribution in tissues of interest. in a pre-clinical setting. Methods: TAK-264, an investigational anti-guanylyl cyclase C (GCC) targeting ADC was synthesized utilizing tritiated Monomethyl auristatin E (MMAE). The tritiated ADC was then conjugated to DTPA, labeled with indium-111 and evaluated in vivo in GCC-positive and GCC-negative tumor-bearing animals. Results: Cryo-imaging Quantitative Autoradiography (CIQA) reveals the time course of drug release from ADC and its distribution into various tumor regions seemingly impenetrablethat are less accessible to the antibody. For GCC-positive tumors, a representative section obtained 96 hours post tracer injection showed only 0.8% of the voxels have co-localized signal versus over 15% of the voxels for a GCC-negative tumor section., suggesting successful and specific cleaving of the toxin in the antigen positive lesions. Conclusion: The combination of a veteran established autoradiography technology with advanced image analysis methodologies affords an experimental tool that can support detailed characterization of ADC tumor penetration and pharmacokinetics. Copyright © 2018 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

One-month apparent diffusion coefficient correlates with response to radiofrequency ablation of hepatocellular carcinoma.

PubMed

Barat, Maxime; Fohlen, Audrey; Cassinotto, Christophe; Jannot, Anne Sophie; Dautry, Raphael; Pelage, Jean-Pierre; Boudiaf, Mourad; Pocard, Marc; Eveno, Clarisse; Taouli, Bachir; Soyer, Philippe; Dohan, Anthony

2017-06-01

To assess whether apparent diffusion coefficient (ADC) values at 1 and 3 months after radiofrequency ablation (RFA) may be associated with a favorable response to therapy for hepatocellular carcinoma (HCC) and liver metastases. Fifty-nine patients with HCC (n = 35) or liver metastases (n = 24) who underwent 1.5T diffusion-weighted magnetic resonance imaging (DWMRI) at 1 and 3 months post-RFA were included. ADC values of patients with local tumor recurrence were compared to those without local recurrence. A subgroup analysis was performed for HCC and metastases. Thirty-eight HCC and 27 metastases were evaluated. The ADC value of HCC at 1 month after RFA was lower in recurrent tumors (0.957 ± 0.229 [SD] × 10 -3 mm 2 ) compared to tumors with complete response (1.414 ± 0.322 [SD] × 10 -3 mm 2 /s, P = 0.006). At multivariate analysis, ADC at 1 month was the single independent variable associated with recurrence for HCC (area under the receiver operating characteristic curve = 0.860). No significant association was observed for liver metastases (P = 0.089). A low ADC value at 1 month after RFA is associated with an early local recurrence of HCC. This study does not confirm that such association exists for hepatic metastases. 3 Technical Efficacy: Stage 2 J. MAGN. RESON. IMAGING 2017;45:1648-1658. © 2016 International Society for Magnetic Resonance in Medicine.

Effect of disease progression on liver apparent diffusion coefficient and T2 values in a murine model of hepatic fibrosis at 11.7 Tesla MRI.

PubMed

Anderson, Stephan W; Jara, Hernan; Ozonoff, Al; O'Brien, Michael; Hamilton, James A; Soto, Jorge A

2012-01-01

To evaluate the effects of hepatic fibrosis on ADC and T(2) values of ex vivo murine liver specimens imaged using 11.7 Tesla (T) MRI. This animal study was IACUC approved. Seventeen male, C57BL/6 mice were divided into control (n = 2) and experimental groups (n = 15), the latter fed a 3, 5-dicarbethoxy-1, 4-dihydrocollidine (DDC) supplemented diet, inducing hepatic fibrosis. Ex vivo liver specimens were imaged using an 11.7T MRI scanner. Spin-echo pulsed field gradient and multi-echo spin-echo acquisitions were used to generate parametric ADC and T(2) maps, respectively. Degrees of fibrosis were determined by the evaluation of a pathologist as well as digital image analysis. Scatterplot graphs comparing ADC and T(2) to degrees of fibrosis were generated and correlation coefficients were calculated. Strong correlation was found between degrees of hepatic fibrosis and ADC with higher degrees of fibrosis associated with lower hepatic ADC values. Moderate correlation between hepatic fibrosis and T(2) values was seen with higher degrees of fibrosis associated with lower T(2) values. Inverse relationships between degrees of fibrosis and both ADC and T(2) are seen, highlighting the utility of these parameters in the ongoing development of an MRI methodology to quantify hepatic fibrosis. Copyright © 2011 Wiley Periodicals, Inc.

Psychometric properties of the Spanish QoL-AD with institutionalized dementia patients and their family caregivers in Spain.

PubMed

León-Salas, B; Logsdon, R G; Olazarán, J; Martínez-Martín, P; The Msu-Adru

2011-08-01

To evaluate the psychometric attributes of the Spanish version of the Quality of Life-Alzheimer's Disease Scale (QoL-AD) in institutionalized patients and family caregivers in Spain. 101 patients (88.1% women; mean age, 83.2  ±  6.3) with Alzheimer's disease (AD) (n = 82) and mixed dementia (n = 19) and their closest family caregivers. Patient-related variables included severity of dementia, cognitive status, perceived general health, quality of life, behavior, apathy, depression, and functional status. QoL-AD acceptability, reliability, and construct validity were analyzed. The mean Mini-Mental State Examination (MMSE) score was 7.2  ±  6.1 and Global Deterioration Scale was: stage four (4%); five (21.2%); six (34.3%); and seven (40.4%). Both, QoL-AD patient version (QoL-ADp) (n = 40; MMSE = 12.0  ±  4.5) and QoL-AD caregiver version (QoL-ADc) (n = 101) lacked significant floor and ceiling effects and the Cronbach α index was 0.90 and 0.86, respectively. The corrected item-total correlation was 0.11-0.68 (QoL-ADc) and 0.28-0.84 (QoL-ADp). Stability was satisfactory for QoL-ADp (intraclass correlation coefficient [ICC]=0.83) but low for QoL-ADc (ICC = 0.51); the standard error of measurement was 2.72 and 4.69. Construct validity was moderate/high for QoL-ADc (QUALID=-0.43; EQ-5D = 0.65), but lower for QoL-ADp. No significant correlations were observed between QoL-ADp and patient variables or QoL-ADc. A low to high association (r = 0.18-0.55) was obtained between QoL-ADc and patient-related measures of neuropsychiatric, function, and cognitive status. Differences in their psychometric attributes, and discrepancy between them, were found for QoL-ADp and QoL-ADc. In patients with AD and advanced dementia, the QoL perceived by the patient could be based on a construct that is different from the traditional QoL construct.

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.

39 CFR 121.3 - Standard Mail.

Code of Federal Regulations, 2013 CFR

2013-07-01

... Facility (SCF) turnaround Standard Mail® pieces accepted at origin before the day-zero Critical Entry Time... origin before the day-zero Critical Entry Time is 4 days when the OPD&C/F and the ADC are the same... before the day-zero Critical Entry Time is 5 days for each remaining 3-digit ZIP Code origin-destination...

Toward Distinguishing Recurrent Tumor From Radiation Necrosis: DWI and MTC in a Gamma Knife–Irradiated Mouse Glioma Model

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

Perez-Torres, Carlos J.; Engelbach, John A.; Cates, Jeremy

Purpose: Accurate noninvasive diagnosis is vital for effective treatment planning. Presently, standard anatomical magnetic resonance imaging (MRI) is incapable of differentiating recurring tumor from delayed radiation injury, as both lesions are hyperintense in both postcontrast T1- and T2-weighted images. Further studies are therefore necessary to identify an MRI paradigm that can differentially diagnose these pathologies. Mouse glioma and radiation injury models provide a powerful platform for this purpose. Methods and Materials: Two MRI contrasts that are widely used in the clinic were chosen for application to a glioma/radiation-injury model: diffusion weighted imaging, from which the apparent diffusion coefficient (ADC) ismore » obtained, and magnetization transfer contrast, from which the magnetization transfer ratio (MTR) is obtained. These metrics were evaluated longitudinally, first in each lesion type alone–glioma versus irradiation – and then in a combined irradiated glioma model. Results: MTR was found to be consistently decreased in all lesions compared to nonlesion brain tissue (contralateral hemisphere), with limited specificity between lesion types. In contrast, ADC, though less sensitive to the presence of pathology, was increased in radiation injury and decreased in tumors. In the irradiated glioma model, ADC also increased immediately after irradiation, but decreased as the tumor regrew. Conclusions: ADC is a better metric than MTR for differentiating glioma from radiation injury. However, MTR was more sensitive to both tumor and radiation injury than ADC, suggesting a possible role in detecting lesions that do not enhance strongly on T1-weighted images.« less

Infarct Volume Prediction by Early Magnetic Resonance Imaging in a Murine Stroke Model Depends on Ischemia Duration and Time of Imaging.

PubMed

Leithner, Christoph; Füchtemeier, Martina; Jorks, Devi; Mueller, Susanne; Dirnagl, Ulrich; Royl, Georg

2015-11-01

Despite standardization of experimental stroke models, final infarct sizes after middle cerebral artery occlusion (MCAO) vary considerably. This introduces uncertainties in the evaluation of drug effects on stroke. Magnetic resonance imaging may detect variability of surgically induced ischemia before treatment and thus improve treatment effect evaluation. MCAO of 45 and 90 minutes induced brain infarcts in 83 mice. During, and 3 and 6 hours after MCAO, we performed multiparametric magnetic resonance imaging. We evaluated time courses of cerebral blood flow, apparent diffusion coefficient (ADC), T1, T2, accuracy of infarct prediction strategies, and impact on statistical evaluation of experimental stroke studies. ADC decreased during MCAO but recovered completely on reperfusion after 45 and partially after 90-minute MCAO, followed by a secondary decline. ADC lesion volumes during MCAO or at 6 hours after MCAO largely determined final infarct volumes for 90 but not for 45 minutes MCAO. The majority of chance findings of final infarct volume differences in random group allocations of animals were associated with significant differences in early ADC lesion volumes for 90, but not for 45-minute MCAO. The prediction accuracy of early magnetic resonance imaging for infarct volumes depends on timing of magnetic resonance imaging and MCAO duration. Variability of the posterior communicating artery in C57Bl6 mice contributes to differences in prediction accuracy between short and long MCAO. Early ADC imaging may be used to reduce errors in the interpretation of post MCAO treatment effects on stroke volumes. © 2015 American Heart Association, Inc.

Utility of whole-lesion ADC histogram metrics for assessing the malignant potential of pancreatic intraductal papillary mucinous neoplasms (IPMNs).

PubMed

Hoffman, David H; Ream, Justin M; Hajdu, Christina H; Rosenkrantz, Andrew B

2017-04-01

To evaluate whole-lesion ADC histogram metrics for assessing the malignant potential of pancreatic intraductal papillary mucinous neoplasms (IPMNs), including in comparison with conventional MRI features. Eighteen branch-duct IPMNs underwent MRI with DWI prior to resection (n = 16) or FNA (n = 2). A blinded radiologist placed 3D volumes-of-interest on the entire IPMN on the ADC map, from which whole-lesion histogram metrics were generated. The reader also assessed IPMN size, mural nodularity, and adjacent main-duct dilation. Benign (low-to-intermediate grade dysplasia; n = 10) and malignant (high-grade dysplasia or invasive adenocarcinoma; n = 8) IPMNs were compared. Whole-lesion ADC histogram metrics demonstrating significant differences between benign and malignant IPMNs were: entropy (5.1 ± 0.2 vs. 5.4 ± 0.2; p = 0.01, AUC = 86%); mean of the bottom 10th percentile (2.2 ± 0.4 vs. 1.6 ± 0.7; p = 0.03; AUC = 81%); and mean of the 10-25th percentile (2.8 ± 0.4 vs. 2.3 ± 0.6; p = 0.04; AUC = 79%). The overall mean ADC, skewness, and kurtosis were not significantly different between groups (p ≥ 0.06; AUC = 50-78%). For entropy (highest performing histogram metric), an optimal threshold of >5.3 achieved a sensitivity of 100%, a specificity of 70%, and an accuracy of 83% for predicting malignancy. No significant difference (p = 0.18-0.64) was observed between benign and malignant IPMNs for cyst size ≥3 cm, adjacent main-duct dilatation, or mural nodule. At multivariable analysis of entropy in combination with all other ADC histogram and conventional MRI features, entropy was the only significant independent predictor of malignancy (p = 0.004). Although requiring larger studies, ADC entropy obtained from 3D whole-lesion histogram analysis may serve as a biomarker for identifying the malignant potential of IPMNs, independent of conventional MRI features.

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.

Syntheses, structures, and properties of two new zinc(II) metal-organic frameworks based on flexible 1,6-bis(2-methyl-imidazole-1-yl)hexane ligand

NASA Astrophysics Data System (ADS)

Jin, Jun-Cheng; Fu, Ai-Yun; Li, Dian; Chang, Wen-Gui; Wu, Ju; Yang, Mei; Xie, Cheng-Gen; Xu, Guang-Nian; Cai, An-Xing; Wu, Ai-Hua

2014-11-01

Two new zinc(II) metal-organic compounds of [Zn(ADC)(bimh)]n (1) and [Zn(ADA)(bimh)]n (2) (H2ADC = 1,3-adamantanedicarboxylic acid, H2ADA = 1,3-adamantanediacetic acid, bimh = 1,6-bis(2-methyl-imidazole-1-yl)-hexane, have been structurally characterized by X-ray diffraction analysis. In compound 1, the zinc(II) ions are bridged by ADC and bimh ligands to form a 1D looped chain. In compound 2, the ADA molecules alternately bridge Zn(II) atoms to form infinite chains, and then the 1D chain is connected through the bimh ligand resulting in an undulating infinite two-dimensional (2D) polymeric network. Additionally, TG analysis, XRPD and fluorescent properties for compounds 1 and 2 are also measured and discussed.

Cancer incidence in a Nationwide HIV/AIDS patient cohort in Taiwan in 1998-2009.

PubMed

Chen, Marcelo; Jen, Ian; Chen, Yi-Hsien; Lin, Ming-Wei; Bhatia, Kishor; Sharp, Gerald B; Law, Matthew G; Arthur Chen, Yi-Ming

2014-04-01

The aims of this study were to investigate the cancer incidence and risk in HIV/AIDS patients relative to the general population in Taiwan. Using Taiwan's National Health Insurance Research Database, 15,269 HIV/AIDS patients were identified between 1998 and 2009. Gender-specific incidence densities (IDs) of both AIDS-defining cancers (ADC) and non-AIDS-defining cancers (NADC) after HIV infection were calculated. Age-, sex-, and period-adjusted standardized incidence rates (SIRs) were obtained using 1.8 million people from the general population as controls. A total of 1117 male and 165 female HIV/AIDS patients were diagnosed with cancer. Non-Hodgkin lymphoma (n = 196; ID = 328.79/100,000 person-years) and cervical cancer (n = 50; ID = 712.08/100,000 person-years) were the most common ADCs, whereas liver cancer (n = 125; ID = 184.52/100,000 person-years) and colon cancer (n = 11; ID = 156.66/100,000 person-years) were the most common NADCs in males and females, respectively. Period-adjusted gender-specific ADC and NADC rates decreased from more than 1500 cases/100,000 person-years to less than 500 cases/100,000 person-years (P < 0.001 for trend). SIRs of ADCs and NADCs also decreased. However, relative to the general population, increased SIRs were still seen for most cancers, many of which had an infectious etiology. The highest SIRs in ADCs and NADCs were seen in Kaposi sarcoma [SIR = 298.0, 95% confidence interval (CI): 258.16 to 343.85] and anal cancer (SIR = 19.10, 95% CI: 12.80 to 27.50). This study showed that although the cancer incidence rates have significantly decreased in the highly active antiretroviral therapy era, HIV/AIDS patients were still at increased risk of ADCs and most NADCs. Cancer screening, especially for infection-related NADCs, should therefore be promoted.

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

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.

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

Early changes in the apparent diffusion coefficient and MMP-9 expression of a cervical carcinoma U14 allograft model following irradiation.

PubMed

Huang, Yecai; Huang, Jianming; Feng, Mei; Ren, Jing; Mi, Kun; Cheng, Jia; Song, Bing; Lang, Jinyi

2017-12-01

A cervical carcinoma allograft model was designed to assess the correlation between early changes in the apparent diffusion coefficient (ADC) values on diffusion-weighted magnetic resonance imaging (DW-MRI) and the expression of matrix metalloproteinase-9 (MMP-9) in tumors. BALB/c mice with U14 tumor allografts on the right rear flank were irradiated with a single 20 Gy dose. All tumor-bearing mice were subjected to DW-MRI, followed by calculation of the ADC values and characterization of the T1 and T2 relaxation time constants. Pre- and post-irradiation ADC values were compared with the tumor volume, and the immunohistochemical staining of MMP-9 and hematoxylin-eosin (HE) staining of tumor allografts. However, no correlations between the pre-treatment ADC values and changes in tumor volumes following irradiation were observed. Notably, the mean ADC value was significantly higher in the irradiated tumors (0.756±0.102×10 -3 mm 2 /sec) as compared with those in the untreated tumors (0.501±0.052×10 -3 mm 2 /sec; P=0.002; r=0.682). Additionally, immunohistochemical staining demonstrated that MMP-9 expression in the irradiated tumors was significantly increased. The mean ADC value was significantly higher in the irradiated tumors with high MMP-9 expression levels (0.815±0.112×10 -3 mm 2 /sec), as compared with in the untreated tumors with low MMP-9 expression levels (0.631±0.068×10 -3 mm 2 /sec). Quantitative analysis determined that the ADC values were correlated with MMP-9 expression (r=0.752; P=0.003). Combined, these results suggest that radiation-induced increases in MMP-9 expression levels may be responsible for early changes in the mean ADC value and the response to irradiation in cervical carcinoma.

Development of radiation tolerant components for the Quench Protection System at CERN

NASA Astrophysics Data System (ADS)

Bitterling, O.; Denz, R.; Steckert, J.; Uznanski, S.

2016-01-01

This paper describes the results of irradiation campaigns with the high resolution Analog to Digital Converter (ADC) ADS1281. This ADC will be used as part of a revised quench detection circuit for the 600 A corrector magnets at the CERN Large Hadron Collider (LHC) . To verify the radiation tolerance of the ADC an irradiation campaign using a proton beam, applying doses up to 3,4 kGy was conducted. The resulting data and an analysis of the found failure modes is discussed in this paper. Several mitigation measures are described that allow to reduce the error rate to levels acceptable for operation as part of the LHC QPS.

Intrahepatic and hilar mass-forming cholangiocarcinoma: Qualitative and quantitative evaluation with diffusion-weighted MR imaging.

PubMed

Fattach, Hassan El; Dohan, Anthony; Guerrache, Youcef; Dautry, Raphael; Boudiaf, Mourad; Hoeffel, Christine; Soyer, Philippe

2015-08-01

To qualitatively and quantitatively analyze the presentation of intrahepatic and hilar mass-forming cholangiocarcinoma with diffusion-weighted magnetic resonance imaging (DW-MRI). Twenty-eight patients with histopathologically proven mass-forming cholangiocarcinoma (hilar, n=17; intrahepatic, n=11) underwent hepatic DW-MRI at 1.5-T using free-breathing acquisition and three b-values (0,400,800s/mm(2)). Cholangiocarcinomas were evaluated qualitatively using visual analysis of DW-MR images and quantitatively with conventional ADC and normalized ADC measurements using liver and spleen as reference organs. All cholangiocarcinomas (28/28; 100%) were visible on DW-MR images. DW-MRI yielded best conspicuity of cholangiocarcinomas than the other MRI sequences (P<0.001). Seven cholangiocarcinomas (7/11; 64%) showed hypointense central area on DW-MR images. Conventional ADC value of cholangiocarcinomas (1.042×10(-3)mm(2)/s±0.221×10(-3)mm(2)/s; range: 0.616×10(-3)mm(2)/s to 2.050×10(-3)mm(2)/s) was significantly lower than that of apparently normal hepatic parenchyma (1.362×10(-3)mm(2)/s±0.187×10(-3)mm(2)/s) (P<0.0001), although substantial overlap was found. No significant differences in ADC and normalized ADC values were found between intrahepatic and hilar cholangiocarcinomas. The use of normalized ADC using the liver as reference organ resulted in the most restricted distribution of ADC values of cholangiocarcinomas (variation coefficient=16.6%). There is a trend towards a common appearance of intrahepatic and hilar mass-forming cholangiocarcinomas on DW-MRI but variations may be observed. Familiarity with these variations may improve the diagnosis of mass-forming cholangiocarcinoma. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Reduced fractional anisotropy on diffusion tensor magnetic resonance imaging after hypoxic-ischemic encephalopathy.

PubMed

Ward, Phil; Counsell, Serena; Allsop, Joanna; Cowan, Frances; Shen, Yuji; Edwards, David; Rutherford, Mary

2006-04-01

Apparent diffusion coefficients (ADC) that are measured by diffusion-weighted imaging are reduced in severe white matter (WM) and in some severe basal ganglia and thalamic (BGT) injury in infants who present with hypoxic-ischemic encephalopathy (HIE). However, ADC values may pseudonormalize or even be high during this time in some less severe but clinically significant injuries. We hypothesized that fractional anisotropy (FA), a measure of the directional diffusivity of water made using diffusion tensor imaging, may be abnormal in these less severe injuries; therefore, the objective of this study was to use diffusion tensor imaging to measure ADC and FA in infants with moderate and severe hypoxic-ischemic brain injury. Twenty infants with HIE and 7 normal control infants were studied. All infants were born at >36 weeks' gestational age, and MRI scans were obtained within 3 weeks of delivery. Data were examined for normality, and comparisons were made using analysis of variance or Kruskal-Wallis as appropriate. During the first week, FA values were decreased with both severe and moderate WM and BGT injury as assessed by conventional imaging, whereas ADC values were reduced only in severe WM injury and some severe BGT injury. Abnormal ADC values pseudonormalized during the second week, whereas FA values continued to decrease. FA is reduced in moderate brain injury after HIE. A low FA may reflect a breakdown in WM organization. Moderate BGT injury may result in atrophy but not overt infarction; it is possible that delayed apoptosis is more marked than immediate necrosis, and this may account for normal early ADC values. The accompanying low FA within some severe and all moderate gray matter lesions, which is associated with significant later impairment, may help to confirm clinically significant abnormality in infants with normal ADC values.

Application of diffusion kurtosis imaging to odontogenic lesions: Analysis of the cystic component.

PubMed

Sakamoto, Junichiro; Kuribayashi, Ami; Kotaki, Shinya; Fujikura, Mamiko; Nakamura, Shin; Kurabayashi, Tohru

2016-12-01

To assess the feasibility of applying diffusion kurtosis imaging (DKI) to common odontogenic lesions and to compare its diagnostic ability versus that of the apparent diffusion coefficient (ADC) for differentiating keratocystic odontogenic tumors (KCOTs) from odontogenic cysts. Altogether, 35 odontogenic lesions were studied: 24 odontogenic cysts, six KCOTs, and five ameloblastomas. The diffusion coefficient (D) and excessive kurtosis (K) were obtained from diffusion-weighted images at b-values of 0, 500, 1000, and 1500 s/mm 2 on 3T magnetic resonance imaging (MRI). The combination of D and K values showing the maximum density of the probable density function was estimated. The ADC was obtained (0 and 1000 s/mm 2 ). Values for odontogenic cysts, KCOTs, and ameloblastomas were compared. Multivariate logistic regression modeling was performed to assess the combination of D and K model versus ADC for differentiating KCOTs from odontogenic cysts. The mean D and ADC were significantly higher for ameloblastomas than for odontogenic cysts or KCOTs (P < 0.05). The mean K was significantly lower for ameloblastomas than for odontogenic cysts or KCOTs (P < 0.05). The mean values of all parameters for odontogenic cysts and KCOTs showed no significant differences (P = 0.369 for ADC, 0.133 for D, and 0.874 for K). The accuracy of the combination of D and K model (76.7%) was superior to that of ADC (66.7%). Use of DKI may be feasible for common odontogenic lesions. A combination of DKI parameters can be expected to increase the accuracy of its diagnostic ability compared with ADC. J. Magn. Reson. Imaging 2016;44:1565-1571. © 2016 International Society for Magnetic Resonance in Medicine.

Differentiation of benign and malignant lesions of the tongue by using diffusion-weighted MRI at 3.0 T.

PubMed

Li, S; Cheng, J; Zhang, Y; Zhang, Z

2015-01-01

Diffusion-weighted MRI (DWI) has been introduced in head and neck lesions and adds important information to the findings obtained through conventional MRI. The purpose of this study was to assess the role of DWI in differentiating benign and malignant lesions of the tongue at 3.0-T field strength imaging. 78 patients with 78 lingual lesions underwent conventional MRI and DWI with b-values of 0 and 1000 s mm(-2) before therapy. The apparent diffusion coefficient (ADC) maps were reconstructed, and the ADC values of the lingual lesions were calculated and compared between benign and malignant lesions of the tongue. The mean ADC values of the malignant tumours, benign solid lesions and cystic lesions were (1.08±0.16)×10(-3), (1.68±0.33)×10(-3) and (2.21±0.35)×10(-3) mm2 s(-1), respectively. The mean ADC values of malignant tumours were significantly lower (p<0.001) than those of benign solid lesions, and the mean ADC values of benign solid lesions were significantly lower (p<0.001) than those of cystic lesions. Receiver operating characteristic analysis showed that when an ADC value<.31×10(-3) mm2 s(-1) was used for predicting malignancy, the highest accuracy of 95.3%, sensitivity of 92.6% and specificity of 97.3% were obtained. ADC values of benign and malignant lesions are significantly different at 3.0-T imaging. DWI can be applied as a complementary tool in the differentiation of benign and malignant lesions of the tongue.

Assessment of Masses of the External Ear With Diffusion-Weighted MR Imaging.

PubMed

Razek, Ahmed Abdel Khalek Abdel

2018-02-01

To assess masses of the external ear with diffusion-weighted MR imaging. Retrospective analysis of 43 consecutive patients with soft tissue mass of the external ear. They underwent single shot diffusion-weighted MR imaging of the ear. The apparent diffusion coefficient (ADC) value of the mass of the external ear was calculated. The final diagnosis was performed by biopsy. The ADC value correlated with the biopsy results. The mean ADC value of malignancy (=27) of external ear (0.95 ± 0.19 × 10 mm/s) was significantly lower (p = 0.001) than that of benign (n = 16) lesions (1.49 ± 0.08 × 10 mm/s). The cutoff ADC used for differentiation of malignancy from benign lesions was 1.18 × 10 mm/s with an area under the curve of 0.959, an accuracy of 93%, a sensitivity of 92%, and specificity of 93%. There was a significant difference in the ADC of well and moderately differentiated malignancy versus poorly and undifferentiated squamous cell carcinoma (p = 0.001), and stages I and II versus stages III and IV (p = 0.04) of squamous cell carcinoma. ADC value is a non-invasive promising imaging parameter that can be used for differentiation of malignancy of the external ear from benign lesions, and grading and staging of squamous cell carcinoma of the external ear.

Locally advanced rectal cancer: diffusion-weighted MR tumour volumetry and the apparent diffusion coefficient for evaluating complete remission after preoperative chemoradiation therapy.

PubMed

Ha, Hong Il; Kim, Ah Young; Yu, Chang Sik; Park, Seong Ho; Ha, Hyun Kwon

2013-12-01

To evaluate DW MR tumour volumetry and post-CRT ADC in rectal cancer as predicting factors of CR using high b values to eliminate perfusion effects. One hundred rectal cancer patients who underwent 1.5-T rectal MR and DW imaging using three b factors (0, 150, and 1,000 s/mm(2)) were enrolled. The tumour volumes of T2-weighted MR and DW images and pre- and post-CRT ADC150-1000 were measured. The diagnostic accuracy of post-CRT ADC, T2-weighted MR, and DW tumour volumetry was compared using ROC analysis. DW MR tumour volumetry was superior to T2-weighted MR volumetry comparing the CR and non-CR groups (P < 0.001). Post-CRT ADC showed a significant difference between the CR and non-CR groups (P = 0.001). The accuracy of DW tumour volumetry (Az = 0.910) was superior to that of T2-weighed MR tumour volumetry (Az = 0.792) and post-CRT ADC (Az = 0.705) in determining CR (P = 0.015). Using a cutoff value for the tumour volume reduction rate of more than 86.8 % on DW MR images, the sensitivity and specificity for predicting CR were 91.4 % and 80 %, respectively. DW MR tumour volumetry after CRT showed significant superiority in predicting CR compared with T2-weighted MR images and post-CRT ADC.

Differentiating Laryngeal Carcinomas from Precursor Lesions by Diffusion-Weighted Magnetic Resonance Imaging at 3.0 T: A Preliminary Study

PubMed Central

Shang, De-Sheng; Ruan, Ling-Xiang; Zhou, Shui-Hong; Bao, Yang-Yang; Cheng, Ke-Jia; Wang, Qin-Ying

2013-01-01

Background Diffusion-weighted magnetic resonance imaging (DWI) has been introduced in head and neck cancers. Due to limitations in the performance of laryngeal DWI, including the complex anatomical structure of the larynx leading to susceptibility effects, the value of DWI in differentiating benign from malignant laryngeal lesions has largely been ignored. We assessed whether a threshold for the apparent diffusion coefficient (ADC) was useful in differentiating preoperative laryngeal carcinomas from precursor lesions by turbo spin-echo (TSE) DWI and 3.0-T magnetic resonance. Methods We evaluated DWI and the ADC value in 33 pathologically proven laryngeal carcinomas and 17 precancerous lesions. Results The sensitivity, specificity, and accuracy were 81.8%, 64.7%, 76.0% by laryngostroboscopy, respectively. The sensitivity, specificity, and accuracy of conventional magnetic resonance imaging were 90.9%, 76.5%, 86.0%, respectively. Qualitative DWI analysis produced sensitivity, specificity, and accuracy values of 100.0, 88.2, and 96.0%, respectively. The ADC values were lower for patients with laryngeal carcinoma (mean 1.195±0.32×10−3 mm2/s) versus those with laryngeal precancerous lesions (mean 1.780±0.32×10−3 mm2/s; P<0.001). ROC analysis showed that the area under the curve was 0.956 and the optimum threshold for the ADC was 1.455×10−3 mm2/s, resulting in a sensitivity of 94.1%, a specificity of 90.9%, and an accuracy of 92.9%. Conclusions Despite some limitations, including the small number of laryngeal carcinomas included, DWI may detect changes in tumor size and shape before they are visible by laryngostroboscopy. The ADC values were lower for patients with laryngeal carcinoma than for those with laryngeal precancerous lesions. The proposed cutoff for the ADC may help distinguish laryngeal carcinomas from laryngeal precancerous lesions. PMID:23874693

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.

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

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.

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

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.

Haralick texture features from apparent diffusion coefficient (ADC) MRI images depend on imaging and pre-processing parameters.

PubMed

Brynolfsson, Patrik; Nilsson, David; Torheim, Turid; Asklund, Thomas; Karlsson, Camilla Thellenberg; Trygg, Johan; Nyholm, Tufve; Garpebring, Anders

2017-06-22

In recent years, texture analysis of medical images has become increasingly popular in studies investigating diagnosis, classification and treatment response assessment of cancerous disease. Despite numerous applications in oncology and medical imaging in general, there is no consensus regarding texture analysis workflow, or reporting of parameter settings crucial for replication of results. The aim of this study was to assess how sensitive Haralick texture features of apparent diffusion coefficient (ADC) MR images are to changes in five parameters related to image acquisition and pre-processing: noise, resolution, how the ADC map is constructed, the choice of quantization method, and the number of gray levels in the quantized image. We found that noise, resolution, choice of quantization method and the number of gray levels in the quantized images had a significant influence on most texture features, and that the effect size varied between different features. Different methods for constructing the ADC maps did not have an impact on any texture feature. Based on our results, we recommend using images with similar resolutions and noise levels, using one quantization method, and the same number of gray levels in all quantized images, to make meaningful comparisons of texture feature results between different subjects.

TROP2 overexpression promotes proliferation and invasion of lung adenocarcinoma cells

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

Li, Zanhua; The Chest Hospital of Jiangxi Province Department of Respiration; Jiang, Xunsheng

2016-01-29

Recent studies suggest that the human trophoblast cell-surface antigen TROP2 is highly expressed in a number of tumours and is correlated with poor prognosis. However, its role in non-small cell lung carcinoma (NSCLC) remains largely unknown. Here we examined TROP2 expression by immunohistochemistry in a series of 68 patients with adenocarcinoma (ADC). We found significantly elevated TROP2 expression in ADC tissues compared with normal lung tissues (P < 0.05), and TROP2 overexpression was significantly associated with TNM (tumour, node, metastasis) stage (P = 0.012), lymph node metastasis (P = 0.038), and histologic grade (P = 0.013). Kaplan–Meier survival analysis revealed that high TROP2 expression correlated with poor prognosismore » (P = 0.046). Multivariate analysis revealed that TROP2 expression was an independent prognostic marker for overall survival of ADC patients. Moreover, TROP2 overexpression enhanced cell proliferation, migration, and invasion in the NSCLC cell line A549, whereas knockdown of TROP2 induced apoptosis and impaired proliferation, migration, and invasion in the PC-9 cells. Altogether, our data suggest that TROP2 plays an important role in promoting ADC and may represent a novel prognostic biomarker and therapeutic target for the disease.« less

Longitudinal 3.0T MRI analysis of changes in lymph node volume and apparent diffusion coefficient in an experimental animal model of metastatic and hyperplastic lymph nodes.

PubMed

Klerkx, Wenche M; Geldof, Albert A; Heintz, A Peter; van Diest, Paul J; Visser, Fredy; Mali, Willem P; Veldhuis, Wouter B

2011-05-01

To perform a longitudinal analysis of changes in lymph node volume and apparent diffusion coefficient (ADC) in healthy, metastatic, and hyperplastic lymph nodes. Three groups of four female Copenhagen rats were studied. Metastasis was induced by injecting cells with a high metastatic potential in their left hind footpad. Reactive nodes were induced by injecting Complete Freund Adjuvant (CFA). Imaging was performed at baseline and at 2, 5, 8, 11, and 14 days after tumor cell injection. Finally, lymph nodes were examined histopathologically. The model was highly efficient in inducing lymphadenopathy: subcutaneous cell or CFA inoculation resulted in ipsilateral metastatic or reactive popliteal lymph nodes in all rats. Metastatic nodal volumes increased exponentially from 5-7 mm(3) at baseline to 25 mm(3) at day 14, while the control node remained 5 mm(3). The hyperplastic nodes showed a rapid volume increase reaching a plateau at day 6. The ADC of metastatic nodes significantly decreased (range 13%-32%), but this decrease was also seen in reactive nodes. Metastatic and hyperplastic lymph nodes differed in terms of enlargement patterns and ADC changes. Enlarged reactive or malignant nodes could not be differentiated based on their ADC values. Copyright © 2011 Wiley-Liss, Inc.

Apparent diffusion coefficient of hyperpolarized (3)He with minimal influence of the residual gas in small animals.

PubMed

Carrero-González, L; Kaulisch, T; Ruiz-Cabello, J; Pérez-Sánchez, J M; Peces-Barba, G; Stiller, D; Rodríguez, I

2012-09-01

The apparent diffusion coefficient (ADC) of hyperpolarized (HP) gases is a parameter that reflects changes in lung microstructure. However, ADC is dependent on many physiological and experimental variables that need to be controlled or specified in order to ensure the reliability and reproducibility of this parameter. A single breath-hold experiment is desirable in order to reduce the amount of consumed HP gas. The application of a positive end-expiratory pressure (PEEP) causes an increase in the residual gas volume. Depending on the applied PEEP, the ratio between the incoming and residual gas volumes will change and the ADC will vary, as long as both gases do not have the same diffusion coefficient. The most standard method for human applications uses air for breathing and a bolus of pure HP (3)He for MRI data acquisition. By applying this method in rats, we have demonstrated that ADC values are strongly dependent on the applied PEEP, and therefore on the residual gas volume in the lung. This outcome will play an important role in studies concerning certain diseases, such as emphysema, which is characterized by an increase in the residual volume. Ventilation with an oxygen-helium mixture (VOHeM) is a proposed single breath-hold method that uses two different gas mixtures (O(2)-(4)He for ventilation and HP (3)He-N(2) for imaging). The concentration of each gas in its respective mixture was calculated in order to obtain the same diffusion coefficient in both mixtures. ADCs obtained from VOHeM are independent of PEEP, thus minimizing the effect of the different residual volumes. Copyright © 2012 John Wiley & Sons, Ltd.

Comparison of non-Gaussian and Gaussian diffusion models of diffusion weighted imaging of rectal cancer at 3.0 T MRI.

PubMed

Zhang, Guangwen; Wang, Shuangshuang; Wen, Didi; Zhang, Jing; Wei, Xiaocheng; Ma, Wanling; Zhao, Weiwei; Wang, Mian; Wu, Guosheng; Zhang, Jinsong

2016-12-09

Water molecular diffusion in vivo tissue is much more complicated. We aimed to compare non-Gaussian diffusion models of diffusion-weighted imaging (DWI) including intra-voxel incoherent motion (IVIM), stretched-exponential model (SEM) and Gaussian diffusion model at 3.0 T MRI in patients with rectal cancer, and to determine the optimal model for investigating the water diffusion properties and characterization of rectal carcinoma. Fifty-nine consecutive patients with pathologically confirmed rectal adenocarcinoma underwent DWI with 16 b-values at a 3.0 T MRI system. DWI signals were fitted to the mono-exponential and non-Gaussian diffusion models (IVIM-mono, IVIM-bi and SEM) on primary tumor and adjacent normal rectal tissue. Parameters of standard apparent diffusion coefficient (ADC), slow- and fast-ADC, fraction of fast ADC (f), α value and distributed diffusion coefficient (DDC) were generated and compared between the tumor and normal tissues. The SEM exhibited the best fitting results of actual DWI signal in rectal cancer and the normal rectal wall (R 2  = 0.998, 0.999 respectively). The DDC achieved relatively high area under the curve (AUC = 0.980) in differentiating tumor from normal rectal wall. Non-Gaussian diffusion models could assess tissue properties more accurately than the ADC derived Gaussian diffusion model. SEM may be used as a potential optimal model for characterization of rectal cancer.

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.

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.

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

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.

Lung injury induced by secondhand smoke exposure detected with hyperpolarized helium-3 diffusion MR.

PubMed

Wang, Chengbo; Mugler, John P; de Lange, Eduard E; Patrie, James T; Mata, Jaime F; Altes, Talissa A

2014-01-01

To determine whether helium-3 diffusion MR can detect the changes in the lungs of healthy nonsmoking individuals who were regularly exposed to secondhand smoke. Three groups were studied (age: 59 ± 9 years): 23 smokers, 37 exposure-to-secondhand-smoke subjects, and 29 control subjects. We measured helium-3 diffusion values at diffusion times from 0.23 to 1.97 s. One-way analysis of variance revealed that the mean area under the helium-3 diffusion curves (ADC AUC) of the smokers was significantly elevated compared with the controls and to the exposure-to-secondhand-smoke subjects (P < 0.001 both). No difference between the mean ADC AUC of the exposure-to-secondhand-smoke subjects and that of the controls was found (P = 0.115). However, application of a receiver operator characteristic-derived rule to classify subjects as either a "control" or a "smoker," based on ADC AUC, revealed that 30% (11/37) of the exposure-to-secondhand subjects were classified as "smokers" indicating an elevation of the ADC AUC. Using helium-3 diffusion MR, elevated ADC values were detected in 30% of nonsmoking healthy subjects who had been regularly exposed to secondhand smoke, supporting the concept that, in susceptible individuals, secondhand smoke causes mild lung damage. Copyright © 2013 Wiley Periodicals, Inc.

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.

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.

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

Performance Analysis for Channel Estimation With 1-Bit ADC and Unknown Quantization Threshold

NASA Astrophysics Data System (ADS)

Stein, Manuel S.; Bar, Shahar; Nossek, Josef A.; Tabrikian, Joseph

2018-05-01

In this work, the problem of signal parameter estimation from measurements acquired by a low-complexity analog-to-digital converter (ADC) with $1$-bit output resolution and an unknown quantization threshold is considered. Single-comparator ADCs are energy-efficient and can be operated at ultra-high sampling rates. For analysis of such systems, a fixed and known quantization threshold is usually assumed. In the symmetric case, i.e., zero hard-limiting offset, it is known that in the low signal-to-noise ratio (SNR) regime the signal processing performance degrades moderately by ${2}/{\\pi}$ ($-1.96$ dB) when comparing to an ideal $\\infty$-bit converter. Due to hardware imperfections, low-complexity $1$-bit ADCs will in practice exhibit an unknown threshold different from zero. Therefore, we study the accuracy which can be obtained with receive data processed by a hard-limiter with unknown quantization level by using asymptotically optimal channel estimation algorithms. To characterize the estimation performance of these nonlinear algorithms, we employ analytic error expressions for different setups while modeling the offset as a nuisance parameter. In the low SNR regime, we establish the necessary condition for a vanishing loss due to missing offset knowledge at the receiver. As an application, we consider the estimation of single-input single-output wireless channels with inter-symbol interference and validate our analysis by comparing the analytic and experimental performance of the studied estimation algorithms. Finally, we comment on the extension to multiple-input multiple-output channel models.

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.

Evaluation of neonatal brain myelination using the T1- and T2-weighted MRI ratio.

PubMed

Soun, Jennifer E; Liu, Michael Z; Cauley, Keith A; Grinband, Jack

2017-09-01

To validate the T1- and T2-weighted (T1w/T2w) MRI ratio technique in evaluating myelin in the neonatal brain. T1w and T2w MR images of 10 term neonates with normal-appearing brain parenchyma were obtained from a single 1.5 Tesla MRI and retrospectively analyzed. T1w/T2w ratio images were created with a postprocessing pipeline and qualitatively compared with standard clinical sequences (T1w, T2w, and apparent diffusion coefficient [ADC]). Quantitative assessment was also performed to assess the ratio technique in detecting areas of known myelination (e.g., posterior limb of the internal capsule) and very low myelination (e.g., optic radiations) using linear regression analysis and the Michelson Contrast equation, a measure of luminance contrast intensity. The ratio image provided qualitative improvements in the ability to visualize regional variation in myelin content of neonates. Linear regression analysis demonstrated a significant inverse relationship between the ratio intensity values and ADC values in the posterior limb of the internal capsule and the optic radiations (R 2  = 0.96 and P < 0.001). The Michelson Contrast equation showed that contrast differences between these two regions for the ratio images were 1.6 times higher than T1w, 2.6 times higher than T2w, and 1.8 times higher than ADC (all P < 0.001). Finally, the ratio improved visualization of the corticospinal tract, one of the earliest myelinated pathways. The T1w/T2w ratio accentuates contrast between myelinated and less myelinated structures and may enhance our diagnostic ability to detect myelination patterns in the neonatal brain. 2 Technical Efficacy: Stage2 J. MAGN. RESON. IMAGING 2017;46:690-696. © 2016 International Society for Magnetic Resonance in Medicine.

Automatic Single Event Effects Sensitivity Analysis of a 13-Bit Successive Approximation ADC

NASA Astrophysics Data System (ADS)

Márquez, F.; Muñoz, F.; Palomo, F. R.; Sanz, L.; López-Morillo, E.; Aguirre, M. A.; Jiménez, A.

2015-08-01

This paper presents Analog Fault Tolerant University of Seville Debugging System (AFTU), a tool to evaluate the Single-Event Effect (SEE) sensitivity of analog/mixed signal microelectronic circuits at transistor level. As analog cells can behave in an unpredictable way when critical areas interact with the particle hitting, there is a need for designers to have a software tool that allows an automatic and exhaustive analysis of Single-Event Effects influence. AFTU takes the test-bench SPECTRE design, emulates radiation conditions and automatically evaluates vulnerabilities using user-defined heuristics. To illustrate the utility of the tool, the SEE sensitivity of a 13-bits Successive Approximation Analog-to-Digital Converter (ADC) has been analysed. This circuit was selected not only because it was designed for space applications, but also due to the fact that a manual SEE sensitivity analysis would be too time-consuming. After a user-defined test campaign, it was detected that some voltage transients were propagated to a node where a parasitic diode was activated, affecting the offset cancelation, and therefore the whole resolution of the ADC. A simple modification of the scheme solved the problem, as it was verified with another automatic SEE sensitivity analysis.

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.

Fast front-end electronics for semiconductor tracking detectors: Trends and perspectives

NASA Astrophysics Data System (ADS)

Rivetti, Angelo

2014-11-01

In the past few years, extensive research efforts pursued by both the industry and the academia have lead to major improvements in the performance of Analog to Digital Converters (ADCs) and Time to Digital Converters (TDCs). ADCs achieving 8-10 bit resolution, 50-100 MHz conversion frequency and less than 1 mW power consumption are the today's standard, while TDCs have reached sub-picosecond time resolution. These results have been made possible by architectural upgrades combined with the use of ultra deep submicron CMOS technologies with minimum feature size of 130 nm or smaller. Front-end ASICs in which a prompt digitization is followed by signal conditioning in the digital domain can now be envisaged also within the tight power budget typically available in high density tracking systems. Furthermore, tracking detectors embedding high resolution timing capabilities are gaining interest. In the paper, ADC's and TDC's developments which are of particular relevance for the design front-end electronics for semiconductor trackers are discussed along with the benefits and challenges of exploiting such high performance building blocks in implementing the next generation of ASICs for high granularity particle detectors.

Prediction of subacute infarct size in acute middle cerebral artery stroke: comparison of perfusion-weighted imaging and apparent diffusion coefficient maps.

PubMed

Drier, Aurélie; Tourdias, Thomas; Attal, Yohan; Sibon, Igor; Mutlu, Gurkan; Lehéricy, Stéphane; Samson, Yves; Chiras, Jacques; Dormont, Didier; Orgogozo, Jean-Marc; Dousset, Vincent; Rosso, Charlotte

2012-11-01

To compare perfusion-weighted (PW) imaging and apparent diffusion coefficient (ADC) maps in prediction of infarct size and growth in patients with acute middle cerebral artery infarct. This study was approved by the local institutional review board. Written informed consent was obtained from all 80 patients. Subsequent infarct volume and growth on follow-up magnetic resonance (MR) images obtained within 6 days were compared with the predictions based on PW images by using a time-to-peak threshold greater than 4 seconds and ADC maps obtained less than 12 hours after middle cerebral artery infarct. ADC- and PW imaging-predicted infarct growth areas and infarct volumes were correlated with subsequent infarct growth and follow-up diffusion-weighted (DW) imaging volumes. The impact of MR imaging time delay on the correlation coefficient between the predicted and subsequent infarct volumes and individual predictions of infarct growth by using receiver operating characteristic curves were assessed. The infarct volume measurements were highly reproducible (concordance correlation coefficient [CCC] of 0.965 and 95% confidence interval [CI]: 0.949, 0.976 for acute DW imaging; CCC of 0.995 and 95% CI: 0.993, 0.997 for subacute DW imaging). The subsequent infarct volume correlated (P<.0001) with ADC- (ρ=0.853) and PW imaging- (ρ=0.669) predicted volumes. The correlation was higher for ADC-predicted volume than for PW imaging-predicted volume (P<.005), but not when the analysis was restricted to patients without recanalization (P=.07). The infarct growth correlated (P<.0001) with PW imaging-DW imaging mismatch (ρ=0.470) and ADC-DW imaging mismatch (ρ=0.438), without significant differences between both methods (P=.71). The correlations were similar among time delays with ADC-predicted volumes but decreased with PW imaging-based volumes beyond the therapeutic window. Accuracies of ADC- and PW imaging-based predictions of infarct growth in an individual prediction were similar (area under the receiver operating characteristic curve [AUC] of 0.698 and 95% CI: 0.585, 0.796 vs AUC of 0.749 and 95% CI: 0.640, 0.839; P=.48). The ADC-based method was as accurate as the PW imaging-based method for evaluating infarct growth and size in the subacute phase. © RSNA, 2012

Non-Invasive Prostate Cancer Characterization with Diffusion-Weighted MRI: Insight from In silico Studies of a Transgenic Mouse Model

PubMed Central

Hill, Deborah K.; Heindl, Andreas; Zormpas-Petridis, Konstantinos; Collins, David J.; Euceda, Leslie R.; Rodrigues, Daniel N.; Moestue, Siver A.; Jamin, Yann; Koh, Dow-Mu; Yuan, Yinyin; Bathen, Tone F.; Leach, Martin O.; Blackledge, Matthew D.

2017-01-01

Diffusion-weighted magnetic resonance imaging (DWI) enables non-invasive, quantitative staging of prostate cancer via measurement of the apparent diffusion coefficient (ADC) of water within tissues. In cancer, more advanced disease is often characterized by higher cellular density (cellularity), which is generally accepted to correspond to a lower measured ADC. A quantitative relationship between tissue structure and in vivo measurements of ADC has yet to be determined for prostate cancer. In this study, we establish a theoretical framework for relating ADC measurements with tissue cellularity and the proportion of space occupied by prostate lumina, both of which are estimated through automatic image processing of whole-slide digital histology samples taken from a cohort of six healthy mice and nine transgenic adenocarcinoma of the mouse prostate (TRAMP) mice. We demonstrate that a significant inverse relationship exists between ADC and tissue cellularity that is well characterized by our model, and that a decrease of the luminal space within the prostate is associated with a decrease in ADC and more aggressive tumor subtype. The parameters estimated from our model in this mouse cohort predict the diffusion coefficient of water within the prostate-tissue to be 2.18 × 10−3 mm2/s (95% CI: 1.90, 2.55). This value is significantly lower than the diffusion coefficient of free water at body temperature suggesting that the presence of organelles and macromolecules within tissues can drastically hinder the random motion of water molecules within prostate tissue. We validate the assumptions made by our model using novel in silico analysis of whole-slide histology to provide the simulated ADC (sADC); this is demonstrated to have a significant positive correlation with in vivo measured ADC (r2 = 0.55) in our mouse population. The estimation of the structural properties of prostate tissue is vital for predicting and staging cancer aggressiveness, but prostate tissue biopsies are painful, invasive, and are prone to complications such as sepsis. The developments made in this study provide the possibility of estimating the structural properties of prostate tissue via non-invasive virtual biopsies from MRI, minimizing the need for multiple tissue biopsies and allowing sequential measurements to be made for prostate cancer monitoring. PMID:29250485

Comparison of Apparent Diffusion Coefficient and Intravoxel Incoherent Motion for Differentiating among Glioblastoma, Metastasis, and Lymphoma Focusing on Diffusion-Related Parameter.

PubMed

Shim, Woo Hyun; Kim, Ho Sung; Choi, Choong-Gon; Kim, Sang Joon

2015-01-01

Brain tumor cellularity has been assessed by using apparent diffusion coefficient (ADC). However, the ADC value might be influenced by both perfusion and true molecular diffusion, and the perfusion effect on ADC can limit the reliability of ADC in the characterization of tumor cellularity, especially, in hypervascular brain tumors. In contrast, the IVIM technique estimates parameter values for diffusion and perfusion effects separately. The purpose of our study was to compare ADC and IVIM for differentiating among glioblastoma, metastatic tumor, and primary CNS lymphoma (PCNSL) focusing on diffusion-related parameter. We retrospectively reviewed the data of 128 patients with pathologically confirmed glioblastoma (n = 55), metastasis (n = 31), and PCNSL (n = 42) prior to any treatment. Two neuroradiologists independently calculated the maximum IVIM-f (fmax) and minimum IVIM-D (Dmin) by using 16 different b-values with a bi-exponential fitting of diffusion signal decay, minimum ADC (ADCmin) by using 0 and 1000 b-values with a mono-exponential fitting and maximum normalized cerebral blood volume (nCBVmax). The differences in fmax, Dmin, nCBVmax, and ADCmin among the three tumor pathologies were determined by one-way ANOVA with multiple comparisons. The fmax and Dmin were correlated to the corresponding nCBV and ADC using partial correlation analysis, respectively. Using a mono-exponential fitting of diffusion signal decay, the mean ADCmin was significantly lower in PCNSL than in glioblastoma and metastasis. However, using a bi-exponential fitting, the mean Dmin did not significantly differ in the three groups. The mean fmax significantly increased in the glioblastomas (reader 1, 0.103; reader 2, 0.109) and the metastasis (reader 1, 0.105; reader 2, 0.107), compared to the primary CNS lymphomas (reader 1, 0.025; reader 2, 0.023) (P < .001 for each). The correlation between fmax and the corresponding nCBV was highest in glioblastoma group, and the correlation between Dmin and the corresponding ADC was highest in primary CNS lymphomas group. Unlike ADC value derived from a mono-exponential fitting of diffusion signal, diffusion-related parametric value derived from a bi-exponential fitting with separation of perfusion effect doesn't differ among glioblastoma, metastasis, and PCNSL.

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

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

Value of 3 Tesla diffusion-weighted magnetic resonance imaging for assessing liver fibrosis

PubMed Central

Papalavrentios, Lavrentios; Sinakos, Emmanouil; Chourmouzi, Danai; Hytiroglou, Prodromos; Drevelegas, Konstantinos; Constantinides, Manos; Drevelegas, Antonios; Talwalkar, Jayant; Akriviadis, Evangelos

2015-01-01

Background Limited data are available regarding the role of magnetic resonance imaging (MRI), particularly the new generation 3 Tesla technology, and especially diffusion-weighted imaging (DWI) in predicting liver fibrosis. The aim of our pilot study was to assess the clinical performance of the apparent diffusion coefficient (ADC) of liver parenchyma for the assessment of liver fibrosis in patients with non-alcoholic fatty liver disease (NAFLD). Methods 18 patients with biopsy-proven NAFLD underwent DWI with 3 Tesla MRI. DWI was performed with single-shot echo-planar technique at b values of 0-500 and 0-1000 s/mm2. ADC was measured in four locations in the liver and the mean ADC value was used for analysis. Staging of fibrosis was performed according to the METAVIR system. Results The median age of patients was 52 years (range 23-73). The distribution of patients in different fibrosis stages was: 0 (n=1), 1 (n=7), 2 (n=1), 3 (n=5), 4 (n=4). Fibrosis stage was poorly associated with ADC at b value of 0-500 s/mm2 (r= -0.30, P=0.27). However it was significantly associated with ADC at b value of 0-1000 s/mm2 (r= -0.57, P=0.01). For this b value (0-1000 s/mm2) the area under receiver-operating characteristic curve was 0.93 for fibrosis stage ≥3 and the optimal ADC cut-off value was 1.16 ×10-3 mm2/s. Conclusion 3 Tesla DWI can possibly predict the presence of advanced fibrosis in patients with NAFLD. PMID:25608776

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

Value of 3 Tesla diffusion-weighted magnetic resonance imaging for assessing liver fibrosis.

PubMed

Papalavrentios, Lavrentios; Sinakos, Emmanouil; Chourmouzi, Danai; Hytiroglou, Prodromos; Drevelegas, Konstantinos; Constantinides, Manos; Drevelegas, Antonios; Talwalkar, Jayant; Akriviadis, Evangelos

2015-01-01

Limited data are available regarding the role of magnetic resonance imaging (MRI), particularly the new generation 3 Tesla technology, and especially diffusion-weighted imaging (DWI) in predicting liver fibrosis. The aim of our pilot study was to assess the clinical performance of the apparent diffusion coefficient (ADC) of liver parenchyma for the assessment of liver fibrosis in patients with non-alcoholic fatty liver disease (NAFLD). 18 patients with biopsy-proven NAFLD underwent DWI with 3 Tesla MRI. DWI was performed with single-shot echo-planar technique at b values of 0-500 and 0-1000 s/mm 2 . ADC was measured in four locations in the liver and the mean ADC value was used for analysis. Staging of fibrosis was performed according to the METAVIR system. The median age of patients was 52 years (range 23-73). The distribution of patients in different fibrosis stages was: 0 (n=1), 1 (n=7), 2 (n=1), 3 (n=5), 4 (n=4). Fibrosis stage was poorly associated with ADC at b value of 0-500 s/mm 2 (r= -0.30, P=0.27). However it was significantly associated with ADC at b value of 0-1000 s/mm 2 (r= -0.57, P=0.01). For this b value (0-1000 s/mm 2 ) the area under receiver-operating characteristic curve was 0.93 for fibrosis stage ≥3 and the optimal ADC cut-off value was 1.16 ×10 -3 mm 2 /s. 3 Tesla DWI can possibly predict the presence of advanced fibrosis in patients with NAFLD.

Age-related apparent diffusion coefficient changes in the normal brain.

PubMed

Watanabe, Memi; Sakai, Osamu; Ozonoff, Al; Kussman, Steven; Jara, Hernán

2013-02-01

To measure the mean diffusional age-related changes of the brain over the full human life span by using diffusion-weighted spin-echo single-shot echo-planar magnetic resonance (MR) imaging and sequential whole-brain apparent diffusion coefficient (ADC) histogram analysis and, secondarily, to build mathematical models of these normal age-related changes throughout human life. After obtaining institutional review board approval, a HIPAA-compliant retrospective search was conducted for brain MR imaging studies performed in 2007 for various clinical indications. Informed consent was waived. The brain data of 414 healthy subjects (189 males and 225 females; mean age, 33.7 years; age range, 2 days to 89.3 years) were obtained with diffusion-weighted spin-echo single-shot echo-planar MR imaging. ADC histograms of the whole brain were generated. ADC peak values, histogram widths, and intracranial volumes were plotted against age, and model parameters were estimated by using nonlinear regression. Four different stages were identified for aging changes in ADC peak values, as characterized by specific mathematical terms: There were age-associated exponential decays for the maturation period and the development period, a constant term for adulthood, and a linear increase for the senescence period. The age dependency of ADC peak value was simulated by using four-term six-coefficient function, including biexponential and linear terms. This model fit the data very closely (R(2) = 0.91). Brain diffusivity as a whole demonstrated age-related changes through four distinct periods of life. These results could contribute to establishing an ADC baseline of the normal brain, covering the full human life span.

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.

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.

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

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.

Altered white matter integrity and development in children with autism: a combined voxel-based morphometry and diffusion imaging study.

PubMed

Mengotti, Paola; D'Agostini, Serena; Terlevic, Robert; De Colle, Cristina; Biasizzo, Elsa; Londero, Danielle; Ferro, Adele; Rambaldelli, Gianluca; Balestrieri, Matteo; Zanini, Sergio; Fabbro, Franco; Molteni, Massimo; Brambilla, Paolo

2011-02-01

A combined protocol of voxel-based morphometry (VBM) and diffusion-weighted imaging (DWI) was applied to investigate the neurodevelopment of gray and white matter in autism. Twenty children with autism (mean age= 7 ± 2.75 years old; age range: 4-14; 2 girls) and 22 matched normally developing children (mean age = 7.68 ± 2.03 years old; age range: 4-11; 2 girls) underwent magnetic resonance imaging (MRI). VBM was employed by applying the Template-o-Matic toolbox (TOM), a new approach which constructs the age-matched customized template for tissue segmentation. Also, the apparent diffusion coefficients (ADC) of water molecules were obtained from the analysis of DWI. Regions of interests (ROIs), standardized at 5 pixels, were placed in cortical lobes and corpus callosum on the non-diffusion weighted echo-planar images (b = 0) and were then automatically transferred to the corresponding maps to obtain the ADC values. Compared to normal children, individuals with autism had significantly: (1) increased white matter volumes in the right inferior frontal gyrus, the right fusiform gyrus, the left precentral and supplementary motor area and the left hippocampus, (2) increased gray matter volumes in the inferior temporal gyri bilaterally, the right inferior parietal cortex, the right superior occipital lobe and the left superior parietal lobule, and (3) decreased gray matter volumes in the right inferior frontal gyrus and the left supplementary motor area. Abnormally increased ADC values in the bilateral frontal cortex and in the left side of the genu of the corpus callosum were also reported in autism. Finally, age correlated negatively with lobar and callosal ADC measurements in individuals with autism, but not in children with normal development. These findings suggest cerebral dysconnectivity in the early phases of autism coupled with an altered white matter maturation trajectory during childhood potentially taking place in the frontal and parietal lobes, which may represent a neurodevelopmental marker of the disorder, possibly accounting for the cognitive and social deficits. Copyright © 2010 Elsevier Inc. All rights reserved.

Nurses' perceptions and experiences at daycare for elderly with stroke.

PubMed

Park, Yeon-Hwan; Han, Hae-Ra

2010-09-01

While adult daycare (ADC) is considered a culturally acceptable model of long-term care in countries with a tradition of family-oriented caregiving, Korea is struggling as soaring needs for ADC outpace qualified staff and regulatory systems. This study aimed to describe Korean daycare nurses' perceptions of key daycare services and their working experiences with stroke patients and their families. A mixed-method design was used. First, we conducted a cross-sectional descriptive survey to assess Korean nurses' perceptions about the importance of daycare services. Then focus group interviews were performed to explore the nurses' experiences at ADC. Seventy of a total of 96 nurses at ADC that specialized in the care of stroke patients responded to the survey (response rate 72.9%) and rated the importance of 11 key daycare service items on a visual analogue scale (0-10). Using a purposive sampling design, 16 eligible nurses were interviewed as a group. The qualitative data from focus group interviews were analyzed using thematic analysis to classify common themes into larger categories. Survey data revealed that the nurses perceived "skilled nursing services,"functional recovery," and "general health counseling" as the most important daycare service areas. Focus group data resulted in five themes: "Providing the same, standard care,"Lack of partnership with family caregivers,"Conflict with other staff: ambiguity of the roles and tasks,"Lack of proper education and training," and "Need for quality control and monitoring." Daycare nurses fully recognized the importance of direct nursing care services that are keys to adequate recovery and rehabilitation of older patients with stroke. However, they experienced substantial barriers to carrying out these services due to role confusion, insufficient number of qualified nursing staff, and lack of partnership with family caregivers. The results provide insight into changing healthcare policy to support daycare nurses in a country with limited resources and regulations. Strategies such as better quality control and monitoring of daycare services, provision of continuing education, and prioritizing key services should be considered as a way to address challenges experienced by daycare nurses.

Development of an ADC radiation tolerance characterization system for the upgrade of the ATLAS LAr calorimeter

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

Liu, Hong-Bin; Chen, Hu-Cheng; Chen, Kai

ATLAS LAr calorimeter will undergo its Phase-I upgrade during the long shutdown (LS2) in 2018, and a new LAr Trigger Digitizer Board (LTDB) will be designed and installed. Several commercial-off-the-shelf (COTS) multi-channel high-speed ADCs have been selected as possible backups of the radiation tolerant ADC ASICs for the LTDB. Here, to evaluate the radiation tolerance of these backup commercial ADCs, we developed an ADC radiation tolerance characterization system, which includes the ADC boards, data acquisition (DAQ) board, signal generator, external power supplies and a host computer. The ADC board is custom designed for different ADCs, with ADC drivers and clockmore » distribution circuits integrated on board. The Xilinx ZC706 FPGA development board is used as a DAQ board. The data from the ADC are routed to the FPGA through the FMC (FPGA Mezzanine Card) connector, de-serialized and monitored by the FPGA, and then transmitted to the host computer through the Gigabit Ethernet. A software program has been developed with Python, and all the commands are sent to the DAQ board through Gigabit Ethernet by this program. Two ADC boards have been designed for the ADC, ADS52J90 from Texas Instruments and AD9249 from Analog Devices respectively. TID tests for both ADCs have been performed at BNL, and an SEE test for the ADS52J90 has been performed at Massachusetts General Hospital (MGH). Test results have been analyzed and presented. The test results demonstrate that this test system is very versatile, and works well for the radiation tolerance characterization of commercial multi-channel high-speed ADCs for the upgrade of the ATLAS LAr calorimeter. It is applicable to other collider physics experiments where radiation tolerance is required as well.« less

Development of an ADC radiation tolerance characterization system for the upgrade of the ATLAS LAr calorimeter

DOE PAGES

Liu, Hong-Bin; Chen, Hu-Cheng; Chen, Kai; ...

2017-02-01

ATLAS LAr calorimeter will undergo its Phase-I upgrade during the long shutdown (LS2) in 2018, and a new LAr Trigger Digitizer Board (LTDB) will be designed and installed. Several commercial-off-the-shelf (COTS) multi-channel high-speed ADCs have been selected as possible backups of the radiation tolerant ADC ASICs for the LTDB. Here, to evaluate the radiation tolerance of these backup commercial ADCs, we developed an ADC radiation tolerance characterization system, which includes the ADC boards, data acquisition (DAQ) board, signal generator, external power supplies and a host computer. The ADC board is custom designed for different ADCs, with ADC drivers and clockmore » distribution circuits integrated on board. The Xilinx ZC706 FPGA development board is used as a DAQ board. The data from the ADC are routed to the FPGA through the FMC (FPGA Mezzanine Card) connector, de-serialized and monitored by the FPGA, and then transmitted to the host computer through the Gigabit Ethernet. A software program has been developed with Python, and all the commands are sent to the DAQ board through Gigabit Ethernet by this program. Two ADC boards have been designed for the ADC, ADS52J90 from Texas Instruments and AD9249 from Analog Devices respectively. TID tests for both ADCs have been performed at BNL, and an SEE test for the ADS52J90 has been performed at Massachusetts General Hospital (MGH). Test results have been analyzed and presented. The test results demonstrate that this test system is very versatile, and works well for the radiation tolerance characterization of commercial multi-channel high-speed ADCs for the upgrade of the ATLAS LAr calorimeter. It is applicable to other collider physics experiments where radiation tolerance is required as well.« less

Development of an ADC radiation tolerance characterization system for the upgrade of the ATLAS LAr calorimeter

NASA Astrophysics Data System (ADS)

Liu, Hong-Bin; Chen, Hu-Cheng; Chen, Kai; Kierstead, James; Lanni, Francesco; Takai, Helio; Jin, Ge

2017-02-01

ATLAS LAr calorimeter will undergo its Phase-I upgrade during the long shutdown (LS2) in 2018, and a new LAr Trigger Digitizer Board (LTDB) will be designed and installed. Several commercial-off-the-shelf (COTS) multi-channel high-speed ADCs have been selected as possible backups of the radiation tolerant ADC ASICs for the LTDB. To evaluate the radiation tolerance of these backup commercial ADCs, we developed an ADC radiation tolerance characterization system, which includes the ADC boards, data acquisition (DAQ) board, signal generator, external power supplies and a host computer. The ADC board is custom designed for different ADCs, with ADC drivers and clock distribution circuits integrated on board. The Xilinx ZC706 FPGA development board is used as a DAQ board. The data from the ADC are routed to the FPGA through the FMC (FPGA Mezzanine Card) connector, de-serialized and monitored by the FPGA, and then transmitted to the host computer through the Gigabit Ethernet. A software program has been developed with Python, and all the commands are sent to the DAQ board through Gigabit Ethernet by this program. Two ADC boards have been designed for the ADC, ADS52J90 from Texas Instruments and AD9249 from Analog Devices respectively. TID tests for both ADCs have been performed at BNL, and an SEE test for the ADS52J90 has been performed at Massachusetts General Hospital (MGH). Test results have been analyzed and presented. The test results demonstrate that this test system is very versatile, and works well for the radiation tolerance characterization of commercial multi-channel high-speed ADCs for the upgrade of the ATLAS LAr calorimeter. It is applicable to other collider physics experiments where radiation tolerance is required as well. Supported by the U. S. Department of Energy (DE-SC001270)

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

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.

[Analysis of tissue-specific differentially methylated genes with differential gene expression in non-small cell lung cancer].

PubMed

Yin, L G; Zou, Z Q; Zhao, H Y; Zhang, C L; Shen, J G; Qi, L; Qi, M; Xue, Z Q

2014-01-01

Adenocarcinoma (ADC) and squamous cell carcinomas (SCC) are two subtypes of non-small cell lung carcinomas which are regarded as the leading cause of cancer-related malignancy worldwide. The aim of this study is to detect the differentially methylated loci (DMLs) and differentially methylated genes (DMGs) of these two tumor sets, and then to illustrate the different expression level of specific methylated genes. Using TCGA database and Illumina HumanMethylation 27 arrays, we first screened the DMGs and DMLs in tumor samples. Then, we explored the BiologicalProcess terms of hypermethylated and hypomethylated genes using Functional Gene Ontology (GO) catalogues. Hypermethylation intensively occurred in CpG-island, whereas hypomethylation was located in non-CpG-island. Most SCC and ADC hypermethylated genes involved GO function of DNA dependenit regulation of transcription, and hypomethylated genes mainly 'enriched in the term of immune responses. Additionally, the expression level of specific differentially methylated genesis distinctbetween ADC and SCC. It is concluded that ADC and SCC have different methylated status that might play an important role in carcinogenesis.

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

Utility of intravoxel incoherent motion diffusion-weighted imaging in predicting early response to concurrent chemoradiotherapy in oesophageal squamous cell carcinoma.

PubMed

Li, F P; Wang, H; Hou, J; Tang, J; Lu, Q; Wang, L L; Yu, X P

2018-05-03

To investigate the utility of intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) in predicting the early response to concurrent chemoradiotherapy (CRT) in oesophageal squamous cell carcinoma (OSCC). Thirty-three patients with OSCC who received CRT underwent IVIM-DWI at three time points (before CRT, at the end of radiotherapy 20 Gy, and immediately after CRT). After CRT, the patients were divided into the responders (complete response or partial response) and the non-responders (stable disease) based on RECIST 1.1. The IVIM-DWI parameters (apparent diffusion coefficient [ADC], true diffusion coefficient [D], the pseudo-diffusion coefficient [D*], and the perfusion fraction [f]) values and their percentage changes (Δvalue) at different time points were compared between the responders and the non-responders. Receiver-operating characteristic (ROC) curve analysis was used to determine the efficacy of IVIM-DWI parameters in identifying the response to CRT. The tumour regression ratio showed negative correlations with ADC pre (r=-0.610, p=0.000), ADC 20 Gy (r=-0.518, p=0.002), D pre (r=-0.584, p=0.000), and D 20 Gy (r=-0.454, p=0.008), and positive correlation with ΔD 20 Gy (r=0.361, p=0.039) and ΔD post (r=0.626, p=0.000). Compared to the non-responders, the responders exhibited lower ADC pre , D pre , ADC 20 Gy , and D 20 Gy , as well as higher ΔADC 20 Gy , ΔD 20 Gy , and ΔD post (all p<0.05). D pre had the highest sensitivity (92.9%) and value of area under the ROC curve (0.865) in differentiating the responders from the non-responders. Diffusion-related IVIM-DWI parameters (ADC and D) are potentially helpful in predicting the early treatment effect of CRT in OSCC. Copyright © 2018 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Diffusion Profiling via a Histogram Approach Distinguishes Low-grade from High-grade Meningiomas, Can Reflect the Respective Proliferative Potential and Progesterone Receptor Status.

PubMed

Gihr, Georg Alexander; Horvath-Rizea, Diana; Garnov, Nikita; Kohlhof-Meinecke, Patricia; Ganslandt, Oliver; Henkes, Hans; Meyer, Hans Jonas; Hoffmann, Karl-Titus; Surov, Alexey; Schob, Stefan

2018-02-01

Presurgical grading, estimation of growth kinetics, and other prognostic factors are becoming increasingly important for selecting the best therapeutic approach for meningioma patients. Diffusion-weighted imaging (DWI) provides microstructural information and reflects tumor biology. A novel DWI approach, histogram profiling of apparent diffusion coefficient (ADC) volumes, provides more distinct information than conventional DWI. Therefore, our study investigated whether ADC histogram profiling distinguishes low-grade from high-grade lesions and reflects Ki-67 expression and progesterone receptor status. Pretreatment ADC volumes of 37 meningioma patients (28 low-grade, 9 high-grade) were used for histogram profiling. WHO grade, Ki-67 expression, and progesterone receptor status were evaluated. Comparative and correlative statistics investigating the association between histogram profiling and neuropathology were performed. The entire ADC profile (p10, p25, p75, p90, mean, median) was significantly lower in high-grade versus low-grade meningiomas. The lower percentiles, mean, and modus showed significant correlations with Ki-67 expression. Skewness and entropy of the ADC volumes were significantly associated with progesterone receptor status and Ki-67 expression. ROC analysis revealed entropy to be the most accurate parameter distinguishing low-grade from high-grade meningiomas. ADC histogram profiling provides a distinct set of parameters, which help differentiate low-grade versus high-grade meningiomas. Also, histogram metrics correlate significantly with histological surrogates of the respective proliferative potential. More specifically, entropy revealed to be the most promising imaging biomarker for presurgical grading. Both, entropy and skewness were significantly associated with progesterone receptor status and Ki-67 expression and therefore should be investigated further as predictors for prognostically relevant tumor biological features. Since absolute ADC values vary between MRI scanners of different vendors and field strengths, their use is more limited in the presurgical setting.

Non-AIDS-Defining Cancer Mortality: Emerging Patterns in the Late HAART Era.

PubMed

Zucchetto, Antonella; Virdone, Saverio; Taborelli, Martina; Grande, Enrico; Camoni, Laura; Pappagallo, Marilena; Regine, Vincenza; Grippo, Francesco; Polesel, Jerry; Dal Maso, Luigino; Suligoi, Barbara; Frova, Luisa; Serraino, Diego

2016-10-01

Non-AIDS-defining cancers (non-ADCs) have become the leading non-AIDS-related cause of death among people with HIV/AIDS. We aimed to quantify the excess risk of cancer-related deaths among Italian people with AIDS (PWA), as compared with people without AIDS (non-PWA). A nationwide, population-based, retrospective cohort study was carried out among 5285 Italian PWA, aged 15-74 years, diagnosed between 2006 and 2011. Date of death and multiple-cause-of-death data were retrieved up to December 2011. Excess mortality, as compared with non-PWA, was estimated using sex- and age-standardized mortality ratios (SMRs) and the corresponding 95% confidence intervals (CIs). Among 1229 deceased PWA, 10.3% reported non-ADCs in the death certificate, including lung (3.1%), and liver (1.4%), cancers. A 7.3-fold (95% CI: 6.1 to 8.7) excess mortality was observed for all non-ADCs combined. Statistically significant SMRs emerged for specific non-ADCs, ie, anus (5 deaths, SMR = 227.6, 95% CI: 73.9 to 531.0), Hodgkin lymphoma (12 deaths, SMR = 122.0, 95% CI: 63.0 to 213.0), unspecified uterus (4 deaths, SMR = 52.5, 95% CI: 14.3 to 134.5), liver (17 deaths, SMR = 13.2, 95% CI: 7.7 to 21.1), skin melanoma (4 deaths, SMR = 10.9, 95% CI: 3.0 to 27.8), lung (38 deaths, SMR = 8.0, 95% CI: 5.7 to 11.0), head and neck (9 deaths, SMR = 7.8, 95% CI: 3.6 to 14.9), leukemia (5 deaths, SMR = 7.6, 95% CI: 2.4 to 17.7), and colon-rectum (10 deaths, SMR = 5.4, 95% CI: 2.6 to 10.0). SMRs for non-ADCs were particularly elevated among PWA infected through injecting drug use. This population-based study documented extremely elevated risks of death for non-ADCs among PWA. These findings stress the need of preventive interventions for both virus-related and non-virus-related cancers among HIV-infected individuals.

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.

Histogram analysis of apparent diffusion coefficient for monitoring early response in patients with advanced cervical cancers undergoing concurrent chemo-radiotherapy.

PubMed

Meng, Jie; Zhu, Lijing; Zhu, Li; Ge, Yun; He, Jian; Zhou, Zhengyang; Yang, Xiaofeng

2017-11-01

Background Apparent diffusion coefficient (ADC) histogram analysis has been widely used in determining tumor prognosis. Purpose To investigate the dynamic changes of ADC histogram parameters during concurrent chemo-radiotherapy (CCRT) in patients with advanced cervical cancers. Material and Methods This prospective study enrolled 32 patients with advanced cervical cancers undergoing CCRT who received diffusion-weighted (DW) magnetic resonance imaging (MRI) before CCRT, at the end of the second and fourth week during CCRT and one month after CCRT completion. The ADC histogram for the entire tumor volume was generated, and a series of histogram parameters was obtained. Dynamic changes of those parameters in cervical cancers were investigated as early biomarkers for treatment response. Results All histogram parameters except AUC low showed significant changes during CCRT (all P < 0.05). There were three variable trends involving different parameters. The mode, 5th, 10th, and 25th percentiles showed similar early increase rates (33.33%, 33.99%, 34.12%, and 30.49%, respectively) at the end of the second week of CCRT. The pre-CCRT 5th and 25th percentiles of the complete response (CR) group were significantly lower than those of the partial response (PR) group. Conclusion A series of ADC histogram parameters of cervical cancers changed significantly at the early stage of CCRT, indicating their potential in monitoring early tumor response to therapy.

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.

77 FR 58774 - New Pallet Preparation Standards for Periodicals

Federal Register 2010, 2011, 2012, 2013, 2014

2012-09-24

... Line 2 information listed below and under 8.6, Pallet Placards. * * * * * [Delete 10.1.5g and 10.1.5h in their entirety and add a new 10.1.5g as follows:] g. SCF through mixed ADC, use 8.10.2h through 8...

Simultaneous PET/MRI in assessing the response to chemo/radiotherapy in head and neck carcinoma: initial experience.

PubMed

Romeo, Valeria; Iorio, Brigida; Mesolella, Massimo; Ugga, Lorenzo; Verde, Francesco; Nicolai, Emanuele; Covello, Mario

2018-06-19

The purpose of the study was to assess by simultaneous positron emission tomography/magnetic resonance imaging (PET/MRI) the response to chemotherapy (CHT) and/or radiotherapy (RT) in patients with head and neck squamous cell carcinoma (HNSCC). Five patients with HNSCC underwent simultaneous PET/MRI examination before and after CHT and/or RT. Standard uptake volume (SUV), apparent diffusion coefficient (ADC), Ktrans, Kep, Ve, and iAUC pre- and post-treatment values were extracted and compared. The response to treatment was assessed according to RECIST criteria and classified as complete response (CR), partial response (PR), stable disease (SD), and progression disease (PD). In patient 1, PR was observed with increased ADC, Ktrans, and Ve values and reduction of SUV, iAUC, and Kep values; during clinical and instrumental follow-up, the patient experienced disease progression. Patient 2, classified as PR, showed increased ADC values and reduction of SUV and all perfusion parameters; follow-up demonstrated disease stability. Patient 3, considered as SD, showed increase of ADC and all perfusion values with a mild decrease of SUV; PD was observed during clinical and instrumental follow-up. Patients 4 and 5 showed a CR with no detectable tumor lesions at post-treatment PET/MRI examination, confirmed by 1-year follow-up. Multiparametric evaluation with simultaneous PET/MRI could be a useful tool to assess and predict the response to CHT and/or RT in patients with HNSCC.

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

Assessment of histological differentiation in gastric cancers using whole-volume histogram analysis of apparent diffusion coefficient maps.

PubMed

Zhang, Yujuan; Chen, Jun; Liu, Song; Shi, Hua; Guan, Wenxian; Ji, Changfeng; Guo, Tingting; Zheng, Huanhuan; Guan, Yue; Ge, Yun; He, Jian; Zhou, Zhengyang; Yang, Xiaofeng; Liu, Tian

2017-02-01

To investigate the efficacy of histogram analysis of the entire tumor volume in apparent diffusion coefficient (ADC) maps for differentiating between histological grades in gastric cancer. Seventy-eight patients with gastric cancer were enrolled in a retrospective 3.0T magnetic resonance imaging (MRI) study. ADC maps were obtained at two different b values (0 and 1000 sec/mm 2 ) for each patient. Tumors were delineated on each slice of the ADC maps, and a histogram for the entire tumor volume was subsequently generated. A series of histogram parameters (eg, skew and kurtosis) were calculated and correlated with the histological grade of the surgical specimen. The diagnostic performance of each parameter for distinguishing poorly from moderately well-differentiated gastric cancers was assessed by using the area under the receiver operating characteristic curve (AUC). There were significant differences in the 5 th , 10 th , 25 th , and 50 th percentiles, skew, and kurtosis between poorly and well-differentiated gastric cancers (P < 0.05). There were correlations between the degrees of differentiation and histogram parameters, including the 10 th percentile, skew, kurtosis, and max frequency; the correlation coefficients were 0.273, -0.361, -0.339, and -0.370, respectively. Among all the histogram parameters, the max frequency had the largest AUC value, which was 0.675. Histogram analysis of the ADC maps on the basis of the entire tumor volume can be useful in differentiating between histological grades for gastric cancer. 4 J. Magn. Reson. Imaging 2017;45:440-449. © 2016 International Society for Magnetic Resonance in Medicine.

Changes in the thalamus in atypical parkinsonism detected using shape analysis and diffusion tensor imaging.

PubMed

Hess, C P; Christine, C W; Apple, A C; Dillon, W P; Aminoff, M J

2014-05-01

The thalamus is interconnected with the nigrostriatal system and cerebral cortex and has a major role in cognitive function and sensorimotor integration. The purpose of this study was to determine how regional involvement of the thalamus differs among Parkinson disease, progressive supranuclear palsy, and corticobasal syndrome. Nine patients with Parkinson disease, 5 with progressive supranuclear palsy, and 6 with corticobasal syndrome underwent 3T MR imaging along with 12 matched, asymptomatic volunteers by using a protocol that included volumetric T1 and diffusion tensor imaging. Acquired data were automatically processed to delineate the margins of the motor and nonmotor thalamic nuclear groups, and measurements of ADC were calculated from the DTI data within these regions. Thalamic volume, shape, and ADC were compared across groups. Thalamic volume was smaller in the progressive supranuclear palsy and corticobasal syndrome groups compared with the Parkinson disease and control groups. Shape analysis revealed that this was mainly due to the diminished size of the lateral thalamus. Overall, ADC measurements were higher in the progressive supranuclear palsy group compared with both the Parkinson disease and control groups, and anatomic subgroup analysis demonstrated that these changes were greater within the motor regions of the thalamus in progressive supranuclear palsy and corticobasal degeneration. Reduced size and increased ADC disproportionately involve the lateral thalamus in progressive supranuclear palsy and corticobasal syndrome, consistent with selective neurodegeneration and atrophy in this region. Because these findings were not observed in Parkinson disease, they may be more specific markers of tau-related neurodegeneration. © 2014 by American Journal of Neuroradiology.

Epidermal growth factor receptor gene mutation as risk factor for recurrence in patients with surgically resected lung adenocarcinoma: a matched-pair analysis.

PubMed

Matsumura, Yuki; Owada, Yuki; Yamaura, Takumi; Muto, Satoshi; Osugi, Jun; Hoshino, Mika; Higuchi, Mitsunori; Ohira, Tetsuya; Suzuki, Hiroyuki; Gotoh, Mitsukazu

2016-08-01

Epidermal growth factor receptor (EGFR) mutation is a robust prognostic factor in patients with lung adenocarcinoma (ADC). However, the role of EGFR mutation status as a recurrence-risk factor remains unknown because the presence of such mutations is associated with other background characteristics. We therefore conducted a matched-pair analysis to compare recurrence-free survival (RFS) in matched cohorts of patients with lung ADC. We enrolled 379 patients who underwent surgical resection for lung ADC between 2005 and 2012. We determined the EGFR mutation status of each tumour. Matching their age, gender, smoking history and pathological stage (pStage), we compared RFS between matched cohorts with and without EGFR mutation (n = 86 each). The median age was 67 years, there were 39 (45%) men, 39 (45%) ex- or current smokers and pStage I: 71 (83%), II: 5 (6%), III: 8 (9%), IV: 2 (2%) in each group. The 3- and 5-year RFS rates in patients with mutant and wild-type EGFR were 85 and 78%, and 74 and 60%, respectively, with significant differences between the groups (P = 0.040). Multivariate analysis identified vascular invasion and lymphatic permeation, but not EGFR mutation status, as independent risk factors for recurrence. EGFR-gene mutation might be a favourable recurrence-risk factor in patients with surgically resected lung ADC, but further studies in larger cohorts are needed to verify this hypothesis. © The Author 2016. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Variability of Target and Normal Structure Delineation Using Multimodality Imaging for Radiation Therapy of Pancreatic Cancer

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

Dalah, Entesar; Moraru, Ion; Paulson, Eric

Purpose: To explore the potential of multimodality imaging (dynamic contrast–enhanced magnetic resonance imaging [DCE-MRI], apparent diffusion-coefficient diffusion-weighted imaging [ADC-DWI], fluorodeoxyglucose positron emission tomography [FDG-PET], and computed tomography) to define the gross tumor volume (GTV) and organs at risk in radiation therapy planning for pancreatic cancer. Delineated volumetric changes of DCE-MRI, ADC-DWI, and FDG-PET were assessed in comparison with the finding on 3-dimensional/4-dimensional CT with and without intravenous contrast, and with pathology specimens for resectable and borderline resectable cases of pancreatic cancer. Methods and Materials: We studied a total of 19 representative patients, whose DCE-MRI, ADC-DWI, and FDG-PET data were reviewed.more » Gross tumor volume and tumor burden/active region inside pancreatic head/neck or body were delineated on MRI (denoted GTV{sub DCE}, and GTV{sub ADC}), a standardized uptake value (SUV) of 2.5, 40%SUVmax, and 50%SUVmax on FDG-PET (GTV2.5, GTV{sub 40%}, and GTV{sub 50%}). Volumes of the pancreas, duodenum, stomach, liver, and kidneys were contoured according to CT (V{sub CT}), T1-weighted MRI (V{sub T1}), and T2-weighted MRI (V{sub T2}) for 7 patients. Results: Significant statistical differences were found between the GTVs from DCE-MRI, ADC-DW, 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) cm{sup 3} for GTV{sub DCE}, GTV{sub ADC}, GTV2.5, GTV{sub 40%}, and GTV{sub 50%}, respectively. The mean difference and range in the measurements of maximum dimension of tumor on DCE-MRI, ADC-DW, 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. The T1- and T2-based volumes for pancreas, duodenum, stomach, and liver were generally smaller compared with those from CT, except for the kidneys. Conclusions: Differences exists between DCE-, ADC-, and FDG-PET–defined target volumes for RT of pancreatic cancer. Organ at risk volumes based on MRI are generally smaller than those based on CT. Further studies combined with pathologic specimens are required to identify the optimal imaging modality or sequence to define GTV.« less

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.

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

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.

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.

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.

Assessment of Activity of Crohn Disease by Diffusion-Weighted Magnetic Resonance Imaging

PubMed Central

Li, Xue-hua; Sun, Can-hui; Mao, Ren; Zhang, Zhong-wei; Jiang, Xiao-song; Pui, Margaret H.; Chen, Min-hu; Li, Zi-ping

2015-01-01

Abstract To assess the diagnostic efficacy of diffusion-weighted MR imaging (DWI) for evaluating inflammatory activity in patients with Crohn's disease (CD). A total of 47 CD patients underwent MR enterography (MRE) and DWI using 3 b values of 50, 400, and 800 s/mm.2 Apparent diffusion coefficients (ADCs) of inflamed and normal bowel wall were calculated. The conventional MRE findings and DWI signal intensities were qualitatively scored from 0 to 3. The correlation between Crohn disease activity index (CDAI) and both ADCs and magnetic resonance imaging scores was analyzed. Receiver-operating characteristic curve analysis was used to determine the diagnostic accuracy of CD activity. Of the 47 patients, 25 were active CD (CDAI≥150) and 22 were inactive (CDAI<150). Diffusion-weighted MR imaging and MRE + DWI scores of active CD were significantly higher than that of inactive CD (both P < 0.001). Apparent diffusion coefficients in inflamed segments of active CD were lower than that of inactive CD (P < 0.001). The DWI scores (r = 0.74, P < 0.001), ADCs (r = −0.71, P < 0.001), MRE scores (r = 0.54, P < 0.001), and MRE + DWI scores (r = 0.66, P < 0.001) were all correlated with CDAI. The areas under the receiver-operating characteristics curves for ADCs, DWI scores, MRE scores, and MRE + DWI scores ranged from 0.83 to 0.98. The threshold ADC value of 1.17 × 10−3 mm2/s allowed differentiation of active from inactive CD with 100% sensitivity and 88% specificity. Diffusion-weighted MR imaging and ADC correlated with CD activity, and had excellent diagnostic accuracy for differentiating active from inactive CD. PMID:26512584

Serial MR diffusion to predict treatment response in high-grade pediatric brain tumors: a comparison of regional and voxel-based diffusion change metrics

PubMed Central

Rodriguez Gutierrez, Daniel; Manita, Muftah; Jaspan, Tim; Dineen, Robert A.; Grundy, Richard G.; Auer, Dorothee P.

2013-01-01

Background Assessment of treatment response by measuring tumor size is known to be a late and potentially confounded response index. Serial diffusion MRI has shown potential for allowing earlier and possibly more reliable response assessment in adult patients, with limited experience in clinical settings and in pediatric brain cancer. We present a retrospective study of clinical MRI data in children with high-grade brain tumors to assess and compare the values of several diffusion change metrics to predict treatment response. Methods Eighteen patients (age range, 1.9–20.6 years) with high-grade brain tumors and serial diffusion MRI (pre- and posttreatment interval range, 1–16 weeks posttreatment) were identified after obtaining parental consent. The following diffusion change metrics were compared with the clinical response status assessed at 6 months: (1) regional change in absolute and normalized apparent diffusivity coefficient (ADC), (2) voxel-based fractional volume of increased (fiADC) and decreased ADC (fdADC), and (3) a new metric based on the slope of the first principal component of functional diffusion maps (fDM). Results Responders (n = 12) differed significantly from nonresponders (n = 6) in all 3 diffusional change metrics demonstrating higher regional ADC increase, larger fiADC, and steeper slopes (P < .05). The slope method allowed the best response prediction (P < .01, η2 = 0.78) with a classification accuracy of 83% for a slope of 58° using receiver operating characteristic (ROC) analysis. Conclusions We demonstrate that diffusion change metrics are suitable response predictors for high-grade pediatric tumors, even in the presence of variable clinical diffusion imaging protocols. PMID:23585630

Impact of blood flow on diffusion coefficients of the human kidney: a time-resolved ECG-triggered diffusion-tensor imaging (DTI) study at 3T.

PubMed

Heusch, Philipp; Wittsack, Hans-Jörg; Kröpil, Patric; Blondin, Dirk; Quentin, Michael; Klasen, Janina; Pentang, Gael; Antoch, Gerald; Lanzman, Rotem S

2013-01-01

To evaluate the impact of renal blood flow on apparent diffusion coefficients (ADC) and fractional anisotropy (FA) using time-resolved electrocardiogram (ECG)-triggered diffusion-tensor imaging (DTI) of the human kidneys. DTI was performed in eight healthy volunteers (mean age 29.1 ± 3.2) using a single slice coronal echoplanar imaging (EPI) sequence (3 b-values: 0, 50, and 300 s/mm(2)) at the timepoint of minimum (20 msec after R wave) and maximum renal blood flow (200 msec after R wave) at 3T. Following 2D motion correction, region of interest (ROI)-based analysis of cortical and medullary ADC- and FA-values was performed. ADC-values of the renal cortex at maximum blood flow (2.6 ± 0.19 × 10(-3) mm(2)/s) were significantly higher than at minimum blood flow (2.2 ± 0.11 × 10(-3) mm(2)/s) (P < 0.001), while medullary ADC-values did not differ significantly (maximum blood flow: 2.2 ± 0.18 × 10(-3) mm(2)/s; minimum blood flow: 2.15 ± 0.14 × 10(-3) mm(2)/s). FA-values of the renal medulla were significantly greater at maximal blood (0.53 ± 0.05) than at minimal blood flow (0.47 ± 0.05) (P < 0.01). In contrast, cortical FA-values were comparable at different timepoints of the cardiac cycle. ADC-values in the renal cortex as well as FA-values in the renal medulla are influenced by renal blood flow. This impact has to be considered when interpreting renal ADC- and FA-values. Copyright © 2012 Wiley Periodicals, Inc.

Characterization and Higher-Order Structure Assessment of an Interchain Cysteine-Based ADC: Impact of Drug Loading and Distribution on the Mechanism of Aggregation.

PubMed

Guo, Jianxin; Kumar, Sandeep; Chipley, Mark; Marcq, Olivier; Gupta, Devansh; Jin, Zhaowei; Tomar, Dheeraj S; Swabowski, Cecily; Smith, Jacquelynn; Starkey, Jason A; Singh, Satish K

2016-03-16

The impact of drug loading and distribution on higher order structure and physical stability of an interchain cysteine-based antibody drug conjugate (ADC) has been studied. An IgG1 mAb was conjugated with a cytotoxic auristatin payload following the reduction of interchain disulfides. The 2-D LC-MS analysis shows that there is a preference for certain isomers within the various drug to antibody ratios (DARs). The physical stability of the unconjugated monoclonal antibody, the ADC, and isolated conjugated species with specific DAR, were compared using calorimetric, thermal, chemical denaturation and molecular modeling techniques, as well as techniques to assess hydrophobicity. The DAR was determined to have a significant impact on the biophysical properties and stability of the ADC. The CH2 domain was significantly perturbed in the DAR6 species, which was attributable to quaternary structural changes as assessed by molecular modeling. At accelerated storage temperatures, the DAR6 rapidly forms higher molecular mass species, whereas the DAR2 and the unconjugated mAb were largely stable. Chemical denaturation study indicates that DAR6 may form multimers while DAR2 and DAR4 primarily exist in monomeric forms in solution at ambient conditions. The physical state differences were correlated with a dramatic increase in the hydrophobicity and a reduction in the surface tension of the DAR6 compared to lower DAR species. Molecular modeling of the various DAR species and their conformers demonstrates that the auristatin-based linker payload directly contributes to the hydrophobicity of the ADC molecule. Higher order structural characterization provides insight into the impact of conjugation on the conformational and colloidal factors that determine the physical stability of cysteine-based ADCs, with implications for process and formulation development.

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...

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

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.

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.

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.

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.

Correlation of simultaneously acquired diffusion-weighted imaging and 2-deoxy-[18F] fluoro-2-D-glucose positron emission tomography of pulmonary lesions in a dedicated whole-body magnetic resonance/positron emission tomography system.

PubMed

Schmidt, Holger; Brendle, Cornelia; Schraml, Christina; Martirosian, Petros; Bezrukov, Ilja; Hetzel, Jürgen; Müller, Mark; Sauter, Alexander; Claussen, Claus D; Pfannenberg, Christina; Schwenzer, Nina F

2013-05-01

Hybrid whole-body magnetic resonance/positron emission tomography (MR/PET) systems are a new diagnostic tool enabling the simultaneous acquisition of morphologic and multiple functional data and thus allowing for a diversified characterization of oncological diseases.The aim of this study was to investigate the image and alignment quality of MR/PET in patients with pulmonary lesions and to compare the congruency of the 2 functional measurements of diffusion-weighted imaging (DWI) in MR imaging and 2-deoxy-[18F] fluoro-2-D-glucose (FDG) uptake in PET. A total of 15 patients were examined with a routine positron emission tomography/computer tomography (PET/CT) protocol and, subsequently, in a whole-body MR/PET scanner allowing for simultaneous PET and MR data acquisition. The PET and MR image quality was assessed visually using a 4-point score (1, insufficient; 4, excellent). The alignment quality of the rigidly registered PET/CT and MR/PET data sets was investigated on the basis of multiple anatomic landmarks of the lung using a scoring system from 1 (no alignment) to 4 (very good alignment). In addition, the alignment quality of the tumor lesions in PET/CT and MR/PET as well as for retrospective fusion of PET from PET/CT and MR images was assessed quantitatively and was compared between lesions strongly or less influenced by respiratory motion. The correlation of the simultaneously acquired DWI and FDG uptake in the pulmonary masses was analyzed using the minimum and mean apparent diffusion coefficient (ADC min and ADC mean) as well as the maximum and mean standardized uptake value (SUV max and SUV mean), respectively. In addition, the correlation of SUV max from PET/CT data was investigated as well. On lesions 3 cm or greater, a voxelwise analysis of ADC and SUV was performed. The visual evaluation revealed excellent image quality of the PET images (mean [SD] score, 3.6 [0.5]) and overall good image quality of DWI (mean [SD] score of 2.5 [0.5] for ADC maps and 2.7 [0.5] for diffusion-weighted images, respectively). The alignment quality of the data sets was very good in both MR/PET and PET/CT without significant differences (overall mean [SD] score of MR/PET, 3.8 [0.4]; PET/CT 3.6 [0.5]). Also, the alignment quality of the tumor lesions showed no significant differences between PET/CT and MR/PET (mean cumulative misalignment of MR/PET, 7.7 mm; PET/CT, 7.0 mm; P = 0.705) but between both modalities and a retrospective fusion (mean cumulative misalignment, 17.1 mm; P = 0.002 and P = 0.008 for PET/CT and MR/PET, respectively). Also, the comparison of the lesions strongly or less influenced by respiratory motion showed significant differences only for the retrospective fusion (21.3 mm vs 11.5 mm, respectively; P = 0.043). The ADC min and SUV max as measures of the cell density and glucose metabolism showed a significant reverse correlation (r = -0.80; P = 0.0006). No significant correlation was found between ADC mean and SUV mean (r = -0.42; P = 0.1392). Also, SUV max from the PET/CT data showed significant reverse correlation to ADC min (r = -0.62; P = 0.019). The voxelwise analysis of 5 pulmonary lesions each showed weak but significant negative correlation between ADC and SUV. Examinations of pulmonary lesions in a simultaneous whole-body MR/PET system provide diagnostic image quality in both modalities. Although DWI and FDG-PET reflect different tissue properties, there may very well be an association between the measures of both methods most probably because of increased cellularity and glucose metabolism of FDG-avid pulmonary lesions. A voxelwise DWI and FDG-PET correlation might provide a more sophisticated spatial characterization of pulmonary lesions.

Structural white matter changes in adolescents and young adults with maple syrup urine disease.

PubMed

Klee, D; Thimm, E; Wittsack, H J; Schubert, D; Primke, R; Pentang, G; Schaper, J; Mödder, U; Antoch, A; Wendel, U; Cohnen, M

2013-11-01

To get insight into the nature of magnetic resonance (MR) white matter abnormalities of patients with classic maple syrup urine disease (MSUD) under diet control. Ten patients with classic MSUD and one with a severe MSUD variant (mean age 21.5 ± 5.1 years) on diet and 11 age and sex-matched healthy subjects were enrolled. Apart from standard MR sequences, diffusion weighted images (DWI), diffusion tensor images (DTI), and magnetization transfer images (MT) were obtained and comparatively analyzed for apparent diffusion coefficient (ADC), tensor fractional anisotropy (FA) and MT maps in 11 regions of interest (ROI) within the white matter. In MSUD patients DWI, DTI and FA showed distinct signal changes in the cerebral hemispheres, the dorsal limb of internal capsule, the brain stem and the central cerebellum. Signal intensity was increased in DWI with a reduced ADC and decreased values for FA. MT did not reveal differences between patients and control subjects. Signal abnormalities in the white matter of adolescents and young adults under diet control may be interpreted as consequence of structural alterations like dysmyelination. The reduced ADC and FA in the white matter with preserved MT indicate a reduction in fiber tracks.

The role of magnetic resonance diffusion-weighted imaging and three-dimensional arterial spin labelling perfusion imaging in the differentiation of parasellar meningioma and cavernous haemangioma.

PubMed

Xiao, Hua-Feng; Lou, Xin; Liu, Meng-Yu; Wang, Yu-Lin; Wang, Yan; Chen, Zhi-Ye; Shi, Kai-Ning; Ma, Lin

2014-08-01

To evaluate the diagnostic value of magnetic resonance diffusion-weighted imaging (DWI) and three-dimensional arterial spin labelling perfusion imaging (3D-ASL) in distinguishing cavernous haemangioma from parasellar meningioma, using histological data as a reference standard. Patients with parasellar meningioma or parasellar cavernous haemangioma underwent conventional T1- and T2-weighted magnetic resonance imaging (MRI) followed by DWI and 3D-ASL using a 3.0 Tesla MRI. The minimum apparent diffusion coefficient (minADC) from DWI and the maximal normalized cerebral blood flow (nCBF) from 3D-ASL were measured in each tumour. Diagnosis was confirmed by histology. MinADC was significantly lower and nCBF significantly higher in meningioma (n = 19) than cavernous haemangioma (n = 15). There was a significant negative correlation between minADC and nCBF (r = -0.605). DWI and 3D-ASL are useful in differentiating cavernous haemangiomas from parasellar meningiomas, particularly in situations when the appearance on conventional MRI sequences is otherwise ambiguous. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

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.

Quantitative apparent diffusion coefficient as a noninvasive imaging biomarker for the differentiation of invasive breast cancer and ductal carcinoma in situ.

PubMed

Bickel, Hubert; Pinker-Domenig, Katja; Bogner, Wolfgang; Spick, Claudio; Bagó-Horváth, Zsuzsanna; Weber, Michael; Helbich, Thomas; Baltzer, Pascal

2015-02-01

The objective of this study was to evaluate whether apparent diffusion coefficient (ADC) obtained through diffusion-weighted imaging magnetic resonance imaging at 3 T can be used as an imaging biomarker to differentiate invasive breast cancer from noninvasive ductal carcinoma in situ (DCIS). One hundred seventy-six histopathologically verified primary malignant breast tumors were retrospectively evaluated in 170 patients. All patients had undergone a standardized 3-T magnetic resonance imaging protocol, containing a diffusion-weighted sequence with 2 b values and a series of dynamic contrast-enhanced T1-weighted sequences. Apparent diffusion coefficient was measured manually by a reader blinded to the histopathological results. The ADC values were correlated with histopathological results. Mean ADC values were compared between invasive cancers and DCIS as well as between different tumor grades. Receiver operating characteristics curves were used to calculate diagnostic performance. There were 155 invasive cancers and 21 noninvasive DCIS. Mean (SD) values differed significantly between the invasive cancers (0.9 [0.15] ×10 mm/s) and the DCIS (1.24 [0.23] ×10 mm/s, P < 0.001). Area under the receiver operating characteristics curve was 0.895 (95% confidence interval [CI], 0.840-0.936). A threshold of 1.01 ×10 mm/s or less allowed an identification of invasive cancers with a sensitivity of 78.06% (95% CI, 70.7%-84.3%) and a specificity of 90.5% (95% CI, 69.6%-98.8%). No significant ADC differences were found among different tumor grades (P > 0.05). Apparent diffusion coefficient could be used as an imaging biomarker for the diagnosis of breast cancer. It seems to be a valuable noninvasive quantitative biomarker to assess breast cancer invasiveness. Thus, ADC measurements provide the potential to reduce overdiagnosis and subsequent overtreatment.

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.

Relationship between pretreatment FDG-PET and diffusion-weighted MRI biomarkers in diffuse large B-cell lymphoma

PubMed Central

de Jong, Antoinette; Kwee, Thomas C; de Klerk, John MH; Adam, Judit A; de Keizer, Bart; Fijnheer, Rob; Kersten, Marie José; Ludwig, Inge; Jauw, Yvonne WS; Zijlstra, Josée M; den Bos, Indra C Pieters - Van; Stoker, Jaap; Hoekstra, Otto S; Nievelstein, Rutger AJ

2014-01-01

The purpose of this study was to determine the correlation between the 18F-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) standardized uptake value (SUV) and the diffusion-weighted magnetic resonance imaging (MRI) apparent diffusion coefficient (ADC) in newly diagnosed diffuse large B-cell lymphoma (DLBCL). Pretreatment FDG-PET and diffusion-weighted MRI of 21 patients with histologically proven DLBCL were prospectively analyzed. In each patient, maximum, mean and peak standardized uptake value (SUV) was measured in the lesion with visually highest FDG uptake and in the largest lesion. Mean ADC (ADCmean, calculated with b-values of 0 and 1000 s/mm2) was measured in the same lesions. Correlations between FDG-PET metrics (SUVmax, SUVmean, SUVpeak) and ADCmean were assessed using Pearson’s correlation coefficients. In the lesions with visually highest FDG uptake, no significant correlations were found between the SUVmax, SUVmean, SUVpeak and the ADCmean (P=0.498, P=0.609 and P=0.595, respectively). In the largest lesions, there were no significant correlations either between the SUVmax, SUVmean, SUVpeak and the ADCmean (P=0.992, P=0.843 and P=0.894, respectively). The results of this study indicate that the glycolytic rate as measured by FDG-PET and changes in water compartmentalization and water diffusion as measured by the ADC are independent biological phenomena in newly diagnosed DLBCL. Further studies are warranted to assess the complementary roles of these different imaging biomarkers in the evaluation and follow-up of DLBCL. PMID:24795837

Diffusion-weighted imaging in relation to morphology on dynamic contrast enhancement MRI: the diagnostic value of characterizing non-puerperal mastitis.

PubMed

Zhang, Lina; Hu, Jiani; Guys, Nicholas; Meng, Jinli; Chu, Jianguo; Zhang, Weisheng; Liu, Ailian; Wang, Shaowu; Song, Qingwei

2018-03-01

To demonstrate the value of diffusion-weighted imaging (DWI) in the characterisation of mastitis lesions. Sixty-one non-puerperal patients with pathologically confirmed single benign mastitis lesions underwent preoperative examinations with conventional MRI and axial DWI. Patients were categorised into three groups: (1) periductal mastitis (PDM), (2) granulomatous lobular mastitis (GLM), and (3) infectious abscess (IAB). Apparent diffusion coefficient (ADC) values of each lesion were recorded. A one-way ANOVA with logistic analysis was performed to compare ADC values and other parameters. Discriminative abilities of DWI modalities were compared using the area under the receiver operating characteristic curve (AUC). P < 0.05 was considered statistically significant. ADC values differed significantly among the three groups (P = 0.003) as well as between PDM and IAB and between PDM and GLM. The distribution of non-mass enhancement on dynamic contrast-enhanced (DCE) MRI differed significantly among the three groups (P = 0.03) but not between any two groups specifically. There were no differences in lesion location, patient age, T 2 WI or DWI signal intensity, enhancement type, non-mass internal enhancement, or mass enhancement characteristics among the three groups. ADC values and the distribution of non-mass enhancement are valuable in classifying mastitis subtypes. • Mastitis subtypes exhibit different characteristics on DWI and DCE MRI. • ADC values are helpful in isolating PDM from other mastitis lesions. • Distribution of non-mass enhancement also has value in comparing mastitis subtypes.

The value of whole lesion ADC histogram profiling to differentiate between morphologically indistinguishable ring enhancing lesions-comparison of glioblastomas and brain abscesses.

PubMed

Horvath-Rizea, Diana; Surov, Alexey; Hoffmann, Karl-Titus; Garnov, Nikita; Vörkel, Cathrin; Kohlhof-Meinecke, Patricia; Ganslandt, Oliver; Bäzner, Hansjörg; Gihr, Georg Alexander; Kalman, Marcell; Henkes, Elina; Henkes, Hans; Schob, Stefan

2018-04-06

Morphologically similar appearing ring enhancing lesions in the brain parenchyma can be caused by a number of distinct pathologies, however, they consistently represent life-threatening conditions. The two most frequently encountered diseases manifesting as such are glioblastoma multiforme (GBM) and brain abscess (BA), each requiring disparate therapeutical approaches. As a result of their morphological resemblance, essential treatment might be significantly delayed or even ommited, in case results of conventional imaging remain inconclusive. Therefore, our study aimed to investigate, whether ADC histogram profiling reliably can distinguish between both entities, thus enhancing the differential diagnostic process and preventing treatment failure in this highly critical context. 103 patients (51 BA, 52 GBM) with histopathologically confirmed diagnosis were enrolled. Pretreatment diffusion weighted imaging (DWI) was obtained in a 1.5T system using b values of 0, 500, and 1000 s/mm 2 . Whole lesion ADC volumes were analyzed using a histogram-based approach. Statistical analysis was performed using SPSS version 23. All investigated parameters were statistically different in comparison of both groups. Most importantly, ADCp10 was able to differentiate reliably between BA and GBM with excellent accuracy (0.948) using a cutpoint value of 70 × 10 -5 mm 2 × s -1 . ADC whole lesion histogram profiling provides a valuable tool to differentiate between morphologically indistinguishable mass lesions. Among the investigated parameters, the 10th percentile of the ADC volume distinguished best between GBM and BA.

FYVE-dependent endosomal targeting of an arrestin-related protein in amoeba.

PubMed

Guetta, Dorian; Langou, Karine; Grunwald, Didier; Klein, Gérard; Aubry, Laurence

2010-12-13

Visual and β-arrestins are scaffolding proteins involved in the regulation of receptor-dependent intracellular signaling and their trafficking. The arrestin superfamilly includes several arrestin domain-containing proteins and the structurally related protein Vps26. In Dictyostelium discoideum, the arrestin-domain containing proteins form a family of six members, namely AdcA to -F. In contrast to canonical arrestins, Dictyostelium Adc proteins show a more complex architecture, as they possess, in addition to the arrestin core, other domains, such as C2, FYVE, LIM, MIT and SAM, which potentially mediate selective interactions with either lipids or proteins. A detailed analysis of AdcA has been performed. AdcA extends on both sides of the arrestin core, in particular by a FYVE domain which mediates selective interactions with PI(3)P, as disclosed by intrinsic fluorescence measurements and lipid overlay assays. Localization studies showed an enrichment of tagged- and endogenous AdcA on the rim of early macropinosomes and phagosomes. This vesicular distribution relies on a functional FYVE domain. Our data also show that the arrestin core binds the ADP-ribosylation factor ArfA, the unique amoebal Arf member, in its GDP-bound conformation. This work describes one of the 6 arrestin domain-containing proteins of Dictyostelium, a novel and atypical member of the arrestin clan. It provides the basis for a better understanding of arrestin-related protein involvement in trafficking processes and for further studies on the expanding roles of arrestins in eukaryotes.

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.

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

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

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

Retrospective analysis of the utility of multiparametric MRI for differentiating between benign and malignant breast lesions in women in China

PubMed Central

Fan, Wei Xiong; Chen, Xiao Feng; Cheng, Feng Yan; Cheng, Ya Bao; Xu, Tai; Zhu, Wen Biao; Zhu, Xiao Lei; Li, Gui Jin; Li, Shuai

2018-01-01

Abstract We explored the utility of time-resolved angiography with interleaved stochastic trajectories dynamic contrast-enhanced magnetic resonance imaging (TWIST DCE-MRI), readout segmentation of long variable echo-trains diffusion-weighted magnetic resonance imaging- diffusion-weighted magnetic resonance imaging (RESOLVE-DWI), and echo-planar imaging- diffusion-weighted magnetic resonance imaging (EPI-DWI) for distinguishing between malignant and benign breast lesions. This retrospective analysis included female patients with breast lesions seen at a single center in China between January 2016 and April 2016. Patients were allocated to a benign or malignant group based on pathologic diagnosis. All patients received routine MRI, RESOLVE-DWI, EPI-DWI, and TWIST DCE-T1WI. Variables measured included quantitative parameters (Ktrans, Kep, and Ve), semiquantitative parameters (rate of contrast enhancement for contrast agent inflow [W-in], rate of contrast decay for contrast agent outflow [W-out], and time-to-peak enhancement after contrast agent injection [TTP]) and apparent diffusion coefficient (ADC) values for RESOLVE-DWI (ADCr) and EPI-DWI (ADCe). Receiver-operating characteristic (ROC) curve analysis was used to evaluate the diagnostic utility of each parameter for differentiating malignant from benign breast lesions. A total of 87 patients were included (benign, n = 20; malignant, n = 67). Compared with the benign group, the malignant group had significantly higher Ktrans, Kep and W-in and significantly lower W-out, TTP, ADCe, and ADCr (all P < .05); Ve was not significantly different between groups. RESOLVE-DWI was superior to conventional EPI-DWI at illustrating lesion boundary and morphology, while ADCr was significantly lower than ADCe in all patients. Kep, W-out, ADCr, and ADCe showed the highest diagnostic efficiency (based on AUC value) for differentiating between benign and malignant lesions. Combining 3 parameters (Kep, W-out, and ADCr) had a higher diagnostic efficiency (AUC, 0.965) than any individual parameter and distinguished between benign and malignant lesions with high sensitivity (91.0%), specificity (95.0%), and accuracy (91.9%). An index combining Kep, W-out, and ADCr could potentially be used for the differential diagnosis of breast lesions. PMID:29369183

Retrospective analysis of the utility of multiparametric MRI for differentiating between benign and malignant breast lesions in women in China.

PubMed

Fan, Wei Xiong; Chen, Xiao Feng; Cheng, Feng Yan; Cheng, Ya Bao; Xu, Tai; Zhu, Wen Biao; Zhu, Xiao Lei; Li, Gui Jin; Li, Shuai

2018-01-01

We explored the utility of time-resolved angiography with interleaved stochastic trajectories dynamic contrast-enhanced magnetic resonance imaging (TWIST DCE-MRI), readout segmentation of long variable echo-trains diffusion-weighted magnetic resonance imaging- diffusion-weighted magnetic resonance imaging (RESOLVE-DWI), and echo-planar imaging- diffusion-weighted magnetic resonance imaging (EPI-DWI) for distinguishing between malignant and benign breast lesions.This retrospective analysis included female patients with breast lesions seen at a single center in China between January 2016 and April 2016. Patients were allocated to a benign or malignant group based on pathologic diagnosis. All patients received routine MRI, RESOLVE-DWI, EPI-DWI, and TWIST DCE-T1WI. Variables measured included quantitative parameters (K, Kep, and Ve), semiquantitative parameters (rate of contrast enhancement for contrast agent inflow [W-in], rate of contrast decay for contrast agent outflow [W-out], and time-to-peak enhancement after contrast agent injection [TTP]) and apparent diffusion coefficient (ADC) values for RESOLVE-DWI (ADCr) and EPI-DWI (ADCe). Receiver-operating characteristic (ROC) curve analysis was used to evaluate the diagnostic utility of each parameter for differentiating malignant from benign breast lesions.A total of 87 patients were included (benign, n = 20; malignant, n = 67). Compared with the benign group, the malignant group had significantly higher K, Kep and W-in and significantly lower W-out, TTP, ADCe, and ADCr (all P < .05); Ve was not significantly different between groups. RESOLVE-DWI was superior to conventional EPI-DWI at illustrating lesion boundary and morphology, while ADCr was significantly lower than ADCe in all patients. Kep, W-out, ADCr, and ADCe showed the highest diagnostic efficiency (based on AUC value) for differentiating between benign and malignant lesions. Combining 3 parameters (Kep, W-out, and ADCr) had a higher diagnostic efficiency (AUC, 0.965) than any individual parameter and distinguished between benign and malignant lesions with high sensitivity (91.0%), specificity (95.0%), and accuracy (91.9%).An index combining Kep, W-out, and ADCr could potentially be used for the differential diagnosis of breast lesions.

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.

Comparison between types I and II epithelial ovarian cancer using histogram analysis of monoexponential, biexponential, and stretched-exponential diffusion models.

PubMed

Wang, Feng; Wang, Yuxiang; Zhou, Yan; Liu, Congrong; Xie, Lizhi; Zhou, Zhenyu; Liang, Dong; Shen, Yang; Yao, Zhihang; Liu, Jianyu

2017-12-01

To evaluate the utility of histogram analysis of monoexponential, biexponential, and stretched-exponential models to a dualistic model of epithelial ovarian cancer (EOC). Fifty-two patients with histopathologically proven EOC underwent preoperative magnetic resonance imaging (MRI) (including diffusion-weighted imaging [DWI] with 11 b-values) using a 3.0T system and were divided into two groups: types I and II. Apparent diffusion coefficient (ADC), true diffusion coefficient (D), pseudodiffusion coefficient (D*), perfusion fraction (f), distributed diffusion coefficient (DDC), and intravoxel water diffusion heterogeneity (α) histograms were obtained based on solid components of the entire tumor. The following metrics of each histogram were compared between two types: 1) mean; 2) median; 3) 10th percentile and 90th percentile. Conventional MRI morphological features were also recorded. Significant morphological features for predicting EOC type were maximum diameter (P = 0.007), texture of lesion (P = 0.001), and peritoneal implants (P = 0.001). For ADC, D, f, DDC, and α, all metrics were significantly lower in type II than type I (P < 0.05). Mean, median, 10th, and 90th percentile of D* were not significantly different (P = 0.336, 0.154, 0.779, and 0.203, respectively). Most histogram metrics of ADC, D, and DDC had significantly higher area under the receiver operating characteristic curve values than those of f and α (P < 0.05) CONCLUSION: It is feasible to grade EOC by morphological features and three models with histogram analysis. ADC, D, and DDC have better performance than f and α; f and α may provide additional information. 4 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2017;46:1797-1809. © 2017 International Society for Magnetic Resonance in Medicine.

Interest of diffusion-weighted echo-planar MR imaging and apparent diffusion coefficient mapping in gynecological malignancies: a review.

PubMed

Levy, Antonin; Medjhoul, Aïcha; Caramella, Caroline; Zareski, Elise; Berges, Oscar; Chargari, Cyrus; Boulet, Bérénice; Bidault, François; Dromain, Clarisse; Balleyguier, Corinne

2011-05-01

Magnetic resonance imaging (MRI) remains the standard modality for the local staging of gynecological malignancies but it has several limitations, particularly for lymph node staging or evaluating peritoneal carcinomatosis. Consequently, there has been a growing interest in functional imaging modalities. Based on molecular diffusion, diffusion-weighted imaging (DWI) is a unique, noninvasive modality that provides excellent tissue contrast and was shown to improve the radiological diagnosis of malignant tumors. Using quantitative apparent diffusion coefficient (ADC) measurement of DWI provides a new tool for better distinguishing malignant tissues from benign tumors. The aim of the present review is to report on the results of DWI for the assessment of patients with gynecological malignancies. An analysis of the literature suggests that DWI studies would improve the diagnosis of cervical and endometrial tumors. It may also improve the assessment of tumor extension in patients with peritoneal carcinomatosis from gynecological malignancies. However, since the signal intensity of some cancers can range from high intensity to low intensity, a degree of uncertainty was demonstrated due to the proximity of the normal uterine myometrium and ovaries. Interestingly, there is also evidence that ADC might improve the follow-up and monitoring of patients who receive anticancer therapies, including chemotherapy or radiation therapy. Copyright © 2011 Wiley-Liss, Inc.

MOVES sensitivity analysis update : Transportation Research Board Summer Meeting 2012 : ADC-20 Air Quality Committee

DOT National Transportation Integrated Search

2012-01-01

OVERVIEW OF PRESENTATION : Evaluation Parameters : EPAs Sensitivity Analysis : Comparison to Baseline Case : MOVES Sensitivity Run Specification : MOVES Sensitivity Input Parameters : Results : Uses of Study

Place of residence does not significantly influence radiological morphology of cervical cancer.

PubMed

Burdan, Franciszek; Mocarska, Agnieszka; Klepacz, Robert; Walocha, Jerzy; Kubiatowski, Tomasz; Surdyka, Dariusz; Kieszko, Dariusz; Patyra, Krzysztof; Żelzowska-Cieślińska, Iwonna; Starosławska, Elżbieta

2017-09-21

Cervical squamous cell carcinoma is one of the most common malignancies of women. Its incidence and morphology was analyzed based on the magnetic resonance (MR) data among rural and urban residents. The study involved 61 Caucasian women (58.26±9.63 years) preliminary diagnosed with a cervical cancer without any previous treatment. Standard MR examination, including diffusion weighted imagining, apparent diffusion coefficient (ADC) value measurement and dynamic contrast enhancement, was performed. The rural residents (n=22) were insignificantly older. Their first and last menstruation were observed later and number of pregnancy was higher than in urban women (n=39). However, the incidence of miscarriage was insignificantly rarer. All the tumour linear diameters as well as its volume were insignificantly higher in rural women. The ADC value of the cervical tumor was insignificantly lower, while ADC of lymphatic nodules was higher in rural women. Insignificant changes in tumour grade between both examined groups were found in histological, clinical and radiological examinations. Place of residence did not influence any clinical symptoms nor tumour volume and its ADC. Colporrhoea and colpodynia were insignificantly more often observed in urban women, while parametrium, urinary bladder and rectal infiltrations were more commonly seen in rural residents. Higher risk of lymphatic spread to the internal iliac and parametral lymphatic nodes was reporte[b]d in the rural community. Cervical cancer had similar morphology and growth pattern, regardless of the place of residence. However, a insignificantly larger tumour size among rural residents may suggest a higher incidence of lymphatic spread, probably as a result of less aaccess to modern health care.

Native mass spectrometry and ion mobility characterization of trastuzumab emtansine, a lysine-linked antibody drug conjugate.

PubMed

Marcoux, Julien; Champion, Thierry; Colas, Olivier; Wagner-Rousset, Elsa; Corvaïa, Nathalie; Van Dorsselaer, Alain; Beck, Alain; Cianférani, Sarah

2015-08-01

Antibody-drug conjugates (ADCs) are biochemotherapeutics consisting of a cytotoxic chemical drug linked covalently to a monoclonal antibody. Two main classes of ADCs, namely cysteine and lysine conjugates, are currently available on the market or involved in clinical trials. The complex structure and heterogeneity of ADCs makes their biophysical characterization challenging. For cysteine conjugates, hydrophobic interaction chromatography is the gold standard technique for studying drug distribution, the naked antibody content, and the average drug to antibody ratio (DAR). For lysine ADC conjugates on the other hand, which are not amenable to hydrophobic interaction chromatography because of their higher heterogeneity, denaturing mass spectrometry (MS) and UV/Vis spectroscopy are the most powerful approaches. We report here the use of native MS and ion mobility (IM-MS) for the characterization of trastuzumab emtansine (T-DM1, Kadcyla(®)). This lysine conjugate is currently being considered for the treatment of human epidermal growth factor receptor 2 (HER2)-positive breast cancer, and combines the anti-HER2 antibody trastuzumab (Herceptin(®)), with the cytotoxic microtubule-inhibiting maytansine derivative, DM1. We show that native MS combined with high-resolution measurements and/or charge reduction is beneficial in terms of the accurate values it provides of the average DAR and the drug load profiles. The use of spectral deconvolution is discussed in detail. We report furthermore the use of native IM-MS to directly determine DAR distribution profiles and average DAR values, as well as a molecular modeling investigation of positional isomers in T-DM1. © 2015 The Protein Society.

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.

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

Effect of adding piperacillin-tazobactam to automated dispensing cabinets on promptness of first-dose antibiotics in hospitalized patients.

PubMed

Lo, Amy; Zhu, Juanqi Nikki; Richman, Mark; Joo, Julianne; Chan, Patrick

2014-10-01

Significant improvements in order-to-administration times for critical first doses of i.v. antibiotic therapy through the use of automated dispensing cabinets (ADCs) are reported. In a retrospective pre-post analysis conducted at a large academic medical center, pharmacy and medical records were reviewed to evaluate average times to administration of first doses of i.v. piperacillin-tazobactam therapy during designated periods before and after the addition of selected i.v. antibiotics to ADCs on patient care units. Inpatients who received a specified i.v. piperacillin-tazobactam formulation were included in the analysis. The primary endpoint was the total time from prescribing to administration; the impact of ADC use on other time intervals (e.g., from scanning of orders to administration, from pharmacist verification and release of orders to administration) was also evaluated. A total of 121 subjects were included in the preimplementation (n = 65) and postimplementation (n = 56) samples. There was a significant 1.7-hour reduction in the mean ± S.D. order-to-administration time (from 4.5 ± 4.1 to 2.9 ± 2.5 hours, p = 0.009) for piperacillin-tazobactam first doses with the use of ADCs. Subgroup analyses showed significant reductions in the mean ± S.D. scan-to-administration time (from 3.3 ± 3.4 to 1.7 ± 1.5 hours, p = 0.001) and release-to-administration time (from 2.4 ± 2.4 to 1.4 ± 1.5 hours, p = 0.034). The addition of a piperacillin-tazobactam product and other commonly used i.v. antibiotics to ADCs was associated with a significantly reduced order-to-administration time for piperacillin-tazobactam first doses. This change was accounted for by a significant reduction in the time between order entry and drug administration. Copyright © 2014 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

Comparison of magnetic resonance elastography and diffusion-weighted imaging for differentiating benign and malignant liver lesions.

PubMed

Hennedige, Tiffany P; Hallinan, James Thomas Patrick Decourcy; Leung, Fiona P; Teo, Lynette Li San; Iyer, Sridhar; Wang, Gang; Chang, Stephen; Madhavan, Krishna Kumar; Wee, Aileen; Venkatesh, Sudhakar K

2016-02-01

Comparison of magnetic resonance elastography (MRE) and diffusion-weighted imaging (DWI) for differentiating malignant and benign focal liver lesions (FLLs). Seventy-nine subjects with 124 FLLs (44 benign and 80 malignant) underwent both MRE and DWI. MRE was performed with a modified gradient-echo sequence and DWI with a free breathing technique (b = 0.500). Apparent diffusion coefficient (ADC) maps and stiffness maps were generated. FLL mean stiffness and ADC values were obtained by placing regions of interest over the FLLs on stiffness and ADC maps. The accuracy of MRE and DWI for differentiation of benign and malignant FLL was compared using receiver operating curve (ROC) analysis. There was a significant negative correlation between stiffness and ADC (r = -0.54, p < 0.0001) of FLLs. Malignant FLLs had significantly higher mean stiffness (7.9kPa vs. 3.1kPa, p < 0.001) and lower mean ADC (129 vs. 200 × 10(-3)mm(2)/s, p < 0.001) than benign FLLs. The sensitivity/specificity/positive predictive value/negative predictive value for differentiating malignant from benign FLLs with MRE (cut-off, >4.54kPa) and DWI (cut-off, <151 × 10(-3)mm(2)/s) were 96.3/95.5/97.5/93.3% (p < 0.001) and 85/81.8/88.3/75% (p < 0.001), respectively. ROC analysis showed significantly higher accuracy for MRE than DWI (0.986 vs. 0.82, p = 0.0016). MRE is significantly more accurate than DWI for differentiating benign and malignant FLLs. • MRE is superior to DWI for differentiating benign and malignant focal liver lesions. • Benign lesions with large fibrous components may have higher stiffness with MRE. • Cholangiocarcinomas tend to have higher stiffness than hepatocellular carcinomas. • Hepatocellular adenomas tend to have lower stiffness than focal nodular hyperplasia. • MRE is superior to conventional MRI in differentiating benign and malignant liver lesions.

Diffusion-weighted imaging (DWI) of hepatocellular carcinomas: a retrospective analysis of the correlation between qualitative and quantitative DWI and tumour grade.

PubMed

Jiang, T; Xu, J H; Zou, Y; Chen, R; Peng, L R; Zhou, Z D; Yang, M

2017-06-01

To evaluate the application of qualitative and quantitative diffusion-weighted imaging (DWI) in predicting the histological grade of hepatocellular carcinoma (HCC). Two hundred and fifty-four patients with pathologically confirmed HCC who underwent hepatic DWI on a 1.5-T platform (b = 0, 600 s/mm 2 ) were evaluated retrospectively. HCCs were divided into well-, moderately, and poorly differentiated groups. The relationships between naked-eye signal intensity (SI), SI values, apparent diffusion coefficient (ADC) values on DWI, and the histopathological differentiation of HCC were analysed. Receiver operating characteristic (ROC) curves were drawn to determine the optimal operating points (OOPs) of the SI and ADC values to predict the tumour grade. A weak negative correlation (r=-0.350, p<0.05) was obtained between naked-eye SI and histological grade. There was a significant difference in mean SI values between well- (68.32±31.71) and moderately (102.39±45.55)/poorly (114.55±32.15) differentiated HCC but not between moderately and poorly differentiated HCC. The OOP of the SI value by ROC curve analysis was 66.5 to predict well-differentiated HCC. The mean ADC values of well-, moderately, and poorly differentiated HCC were 1.67±0.13×10 -3 , 1.31±0.16×10 -3 , and 1.08±0.11×10 -3  mm 2 /s, respectively, with significant differences between any two combinations of groups. The OOPs of ADC to diagnose well- and poorly differentiated HCC were 1.5×10 -3 and 1.24×10 -3  mm 2 /s, respectively. Qualitative and quantitative SI and ADC values at DWI may be useful to estimate the histological grade of HCC preoperatively and non-invasively. Copyright © 2017 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Development of multichannel analyzer using sound card ADC for nuclear spectroscopy system

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

Ibrahim, Maslina Mohd; Yussup, Nolida; Lombigit, Lojius

This paper describes the development of Multi-Channel Analyzer (MCA) using sound card analogue to digital converter (ADC) for nuclear spectroscopy system. The system was divided into a hardware module and a software module. Hardware module consist of detector NaI (Tl) 2” by 2”, Pulse Shaping Amplifier (PSA) and a build in ADC chip from readily available in any computers’ sound system. The software module is divided into two parts which are a pre-processing of raw digital input and the development of the MCA software. Band-pass filter and baseline stabilization and correction were implemented for the pre-processing. For the MCA development,more » the pulse height analysis method was used to process the signal before displaying it using histogram technique. The development and tested result for using the sound card as an MCA are discussed.« less

True progression versus pseudoprogression in the treatment of glioblastomas: a comparison study of normalized cerebral blood volume and apparent diffusion coefficient by histogram analysis.

PubMed

Song, Yong Sub; Choi, Seung Hong; Park, Chul-Kee; Yi, Kyung Sik; Lee, Woong Jae; Yun, Tae Jin; Kim, Tae Min; Lee, Se-Hoon; Kim, Ji-Hoon; Sohn, Chul-Ho; Park, Sung-Hye; Kim, Il Han; Jahng, Geon-Ho; Chang, Kee-Hyun

2013-01-01

The purpose of this study was to differentiate true progression from pseudoprogression of glioblastomas treated with concurrent chemoradiotherapy (CCRT) with temozolomide (TMZ) by using histogram analysis of apparent diffusion coefficient (ADC) and normalized cerebral blood volume (nCBV) maps. Twenty patients with histopathologically proven glioblastoma who had received CCRT with TMZ underwent perfusion-weighted imaging and diffusion-weighted imaging (b = 0, 1000 sec/mm(2)). The corresponding nCBV and ADC maps for the newly visible, entirely enhancing lesions were calculated after the completion of CCRT with TMZ. Two observers independently measured the histogram parameters of the nCBV and ADC maps. The histogram parameters between the true progression group (n = 10) and the pseudoprogression group (n = 10) were compared by use of an unpaired Student's t test and subsequent multivariable stepwise logistic regression analysis to determine the best predictors for the differential diagnosis between the two groups. Receiver operating characteristic analysis was employed to determine the best cutoff values for the histogram parameters that proved to be significant predictors for differentiating true progression from pseudoprogression. Intraclass correlation coefficient was used to determine the level of inter-observer reliability for the histogram parameters. The 5th percentile value (C5) of the cumulative ADC histograms was a significant predictor for the differential diagnosis between true progression and pseudoprogression (p = 0.044 for observer 1; p = 0.011 for observer 2). Optimal cutoff values of 892 × 10(-6) mm(2)/sec for observer 1 and 907 × 10(-6) mm(2)/sec for observer 2 could help differentiate between the two groups with a sensitivity of 90% and 80%, respectively, a specificity of 90% and 80%, respectively, and an area under the curve of 0.880 and 0.840, respectively. There was no other significant differentiating parameter on the nCBV histograms. Inter-observer reliability was excellent or good for all histogram parameters (intraclass correlation coefficient range: 0.70-0.99). The C5 of the cumulative ADC histogram can be a promising parameter for the differentiation of true progression from pseudoprogression of newly visible, entirely enhancing lesions after CCRT with TMZ for glioblastomas.

True Progression versus Pseudoprogression in the Treatment of Glioblastomas: A Comparison Study of Normalized Cerebral Blood Volume and Apparent Diffusion Coefficient by Histogram Analysis

PubMed Central

Song, Yong Sub; Park, Chul-Kee; Yi, Kyung Sik; Lee, Woong Jae; Yun, Tae Jin; Kim, Tae Min; Lee, Se-Hoon; Kim, Ji-Hoon; Sohn, Chul-Ho; Park, Sung-Hye; Kim, Il Han; Jahng, Geon-Ho; Chang, Kee-Hyun

2013-01-01

Objective The purpose of this study was to differentiate true progression from pseudoprogression of glioblastomas treated with concurrent chemoradiotherapy (CCRT) with temozolomide (TMZ) by using histogram analysis of apparent diffusion coefficient (ADC) and normalized cerebral blood volume (nCBV) maps. Materials and Methods Twenty patients with histopathologically proven glioblastoma who had received CCRT with TMZ underwent perfusion-weighted imaging and diffusion-weighted imaging (b = 0, 1000 sec/mm2). The corresponding nCBV and ADC maps for the newly visible, entirely enhancing lesions were calculated after the completion of CCRT with TMZ. Two observers independently measured the histogram parameters of the nCBV and ADC maps. The histogram parameters between the true progression group (n = 10) and the pseudoprogression group (n = 10) were compared by use of an unpaired Student's t test and subsequent multivariable stepwise logistic regression analysis to determine the best predictors for the differential diagnosis between the two groups. Receiver operating characteristic analysis was employed to determine the best cutoff values for the histogram parameters that proved to be significant predictors for differentiating true progression from pseudoprogression. Intraclass correlation coefficient was used to determine the level of inter-observer reliability for the histogram parameters. Results The 5th percentile value (C5) of the cumulative ADC histograms was a significant predictor for the differential diagnosis between true progression and pseudoprogression (p = 0.044 for observer 1; p = 0.011 for observer 2). Optimal cutoff values of 892 × 10-6 mm2/sec for observer 1 and 907 × 10-6 mm2/sec for observer 2 could help differentiate between the two groups with a sensitivity of 90% and 80%, respectively, a specificity of 90% and 80%, respectively, and an area under the curve of 0.880 and 0.840, respectively. There was no other significant differentiating parameter on the nCBV histograms. Inter-observer reliability was excellent or good for all histogram parameters (intraclass correlation coefficient range: 0.70-0.99). Conclusion The C5 of the cumulative ADC histogram can be a promising parameter for the differentiation of true progression from pseudoprogression of newly visible, entirely enhancing lesions after CCRT with TMZ for glioblastomas. PMID:23901325

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.

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.

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.

Diffusion-weighted magnetic resonance imaging in cancer: Reported apparent diffusion coefficients, in-vitro and in-vivo reproducibility

PubMed Central

Jafar, Maysam M; Parsai, Arman; Miquel, Marc E

2016-01-01

There is considerable disparity in the published apparent diffusion coefficient (ADC) values across different anatomies. Institutions are increasingly assessing repeatability and reproducibility of the derived ADC to determine its variation, which could potentially be used as an indicator in determining tumour aggressiveness or assessing tumour response. In this manuscript, a review of selected articles published to date in healthy extra-cranial body diffusion-weighted magnetic resonance imaging is presented, detailing reported ADC values and discussing their variation across different studies. In total 115 studies were selected including 28 for liver parenchyma, 15 for kidney (renal parenchyma), 14 for spleen, 13 for pancreatic body, 6 for gallbladder, 13 for prostate, 13 for uterus (endometrium, myometrium, cervix) and 13 for fibroglandular breast tissue. Median ADC values in selected studies were found to be 1.28 × 10-3 mm2/s in liver, 1.94 × 10-3 mm2/s in kidney, 1.60 × 10-3 mm2/s in pancreatic body, 0.85 × 10-3 mm2/s in spleen, 2.73 × 10-3 mm2/s in gallbladder, 1.64 × 10-3 mm2/s and 1.31 × 10-3 mm2/s in prostate peripheral zone and central gland respectively (combined median value of 1.54×10-3 mm2/s), 1.44 × 10-3 mm2/s in endometrium, 1.53 × 10-3 mm2/s in myometrium, 1.71 × 10-3 mm2/s in cervix and 1.92 × 10-3 mm2/s in breast. In addition, six phantom studies and thirteen in vivo studies were summarized to compare repeatability and reproducibility of the measured ADC. All selected phantom studies demonstrated lower intra-scanner and inter-scanner variation compared to in vivo studies. Based on the findings of this manuscript, it is recommended that protocols need to be optimised for the body part studied and that system-induced variability must be established using a standardized phantom in any clinical study. Reproducibility of the measured ADC must also be assessed in a volunteer population, as variations are far more significant in vivo compared with phantom studies. PMID:26834942

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.

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.

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.

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.

Clinical Utility of Multimodality Imaging with Dynamic Contrast-Enhanced MRI, Diffusion-Weighted MRI, and 18F-FDG PET/CT for the Prediction of Neck Control in Oropharyngeal or Hypopharyngeal Squamous Cell Carcinoma Treated with Chemoradiation

PubMed Central

Chan, Sheng-Chieh; Lin, Yu-Chun; Yen, Tzu-Chen; Liao, Chun-Ta; Chang, Joseph Tung-Chieh; Ko, Sheung-Fat; Wang, Hung- Ming; Chang, Chee-Jen; Wang, Jiun-Jie

2014-01-01

The clinical usefulness of pretreatment imaging techniques for predicting neck control in patients with oropharyngeal or hypopharyngeal squamous cell carcinoma (OHSCC) treated with chemoradiation remains unclear. In this prospective study, we investigated the role of pretreatment dynamic contrast-enhanced perfusion MR imaging (DCE-PWI), diffusion-weighted MR imaging (DWI), and [18F]fluorodeoxyglucose-positron emission tomography (18F-FDG PET)/CT derived imaging markers for the prediction of neck control in OHSCC patients treated with chemoradiation. Patients with untreated OHSCC scheduled for chemoradiation between August, 2010 and July, 2012 were eligible for the study. Clinical variables and the following imaging parameters of metastatic neck lymph nodes were examined in relation to neck control: transfer constant, volume of blood plasma, and volume of extracellular extravascular space (Ve) on DCE-PWI; apparent diffusion coefficient (ADC) on DWI; maximum standardized uptake value, metabolic tumor volume, and total lesion glycolysis on 18F-FDG PET/CT. There were 69 patients (37 with oropharynx SCC and 32 with hypopharynx SCC) with successful pretreatment DCE-PWI and DWI available for analysis. After a median follow-up of 31 months, 25 (36.2%) participants had neck failure. Multivariate analysis identified hemoglobin level <14.3 g/dL (P = 0.019), Ve <0.23 (P = 0.040), and ADC >1.14×10−3 mm2/s (P = 0.003) as independent prognostic factors for 3-year neck control. A prognostic scoring system was formulated by summing up the three significant predictors of neck control. Patients with scores of 2–3 had significantly poorer neck control and overall survival rates than patients with scores of 0–1. We conclude that hemoglobin levels, Ve, and ADC are independent pretreatment prognostic factors for neck control in OHSCC treated with chemoradiation. Their combination may identify a subgroup of patients at high risk of developing neck failure. PMID:25531391

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.

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.

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.

Updating the evidence base on the operational costs of supplementary immunization activities for current and future accelerated disease control, elimination and eradication efforts

PubMed Central

2014-01-01

Background To achieve globally or regionally defined accelerated disease control, elimination and eradication (ADC/E/E) goals against vaccine-preventable diseases requires complementing national routine immunization programs with intensive, time-limited, and targeted Supplementary Immunization Activities (SIAs). Many global and country-level SIA costing efforts have historically relied on what are now outdated benchmark figures. Mobilizing adequate resources for successful implementation of SIAs requires updated estimates of non-vaccine costs per target population. Methods This assessment updates the evidence base on the SIA operational costs through a review of literature between 1992 and 2012, and an analysis of actual expenditures from 142 SIAs conducted between 2004 and 2011 and documented in country immunization plans. These are complemented with an analysis of budgets from 31 SIAs conducted between 2006 and 2011 in order to assess the proportion of total SIA costs per person associated with various cost components. All results are presented in 2010 US dollars. Results Existing evidence indicate that average SIA operational costs were usually less than US$0.50 per person in 2010 dollars. However, the evidence is sparse, non-standardized, and largely out of date. Average operational costs per person generated from our analysis of country immunization plans are consistently higher than published estimates, approaching US$1.00 for injectable vaccines. The results illustrate that the benchmarks often used to project needs underestimate the true costs of SIAs and the analysis suggests that SIA operational costs have been increasing over time in real terms. Our assessment also illustrates that operational costs vary across several dimensions. Variations in the actual costs of SIAs likely to reflect the extents to which economies of scale associated with campaign-based delivery can be attained, the underlying strength of the immunization program, sensitivities to the relative ease of vaccine administration (i.e. orally, or by injection), and differences in disease-specific programmatic approaches. The assessment of SIA budgets by cost component illustrates that four cost drivers make up the largest proportion of costs across all vaccines: human resources, program management, social mobilization, and vehicles and transportation. These findings suggest that SIAs leverage existing health system infrastructure, reinforcing the fact that strong routine immunization programs are an important pre-requisite for achieving ADC/E/E goals. Conclusions The results presented here will be useful for national and global-level actors involved in planning, budgeting, resource mobilization, and financing of SIAs in order to create more realistic assessments of resource requirements for both existing ADC/E/E efforts as well as for new vaccines that may deploy a catch-up campaign-based delivery component. However, limitations of our analysis suggest a need to conduct further research into operational costs of SIAs. Understanding the changing face of delivery costs and cost structures for SIAs will continue to be critical to avoid funding gaps and in order to improve vaccination coverage, reduce health inequities, and achieve the ADC/E/E goals many of which have been endorsed by the World Health Assembly and are included in the Decade of Vaccines Global Vaccine Action Plan. PMID:24450832

Updating the evidence base on the operational costs of supplementary immunization activities for current and future accelerated disease control, elimination and eradication efforts.

PubMed

Gandhi, Gian; Lydon, Patrick

2014-01-22

To achieve globally or regionally defined accelerated disease control, elimination and eradication (ADC/E/E) goals against vaccine-preventable diseases requires complementing national routine immunization programs with intensive, time-limited, and targeted Supplementary Immunization Activities (SIAs). Many global and country-level SIA costing efforts have historically relied on what are now outdated benchmark figures. Mobilizing adequate resources for successful implementation of SIAs requires updated estimates of non-vaccine costs per target population. This assessment updates the evidence base on the SIA operational costs through a review of literature between 1992 and 2012, and an analysis of actual expenditures from 142 SIAs conducted between 2004 and 2011 and documented in country immunization plans. These are complemented with an analysis of budgets from 31 SIAs conducted between 2006 and 2011 in order to assess the proportion of total SIA costs per person associated with various cost components. All results are presented in 2010 US dollars. Existing evidence indicate that average SIA operational costs were usually less than US$0.50 per person in 2010 dollars. However, the evidence is sparse, non-standardized, and largely out of date. Average operational costs per person generated from our analysis of country immunization plans are consistently higher than published estimates, approaching US$1.00 for injectable vaccines. The results illustrate that the benchmarks often used to project needs underestimate the true costs of SIAs and the analysis suggests that SIA operational costs have been increasing over time in real terms. Our assessment also illustrates that operational costs vary across several dimensions. Variations in the actual costs of SIAs likely to reflect the extents to which economies of scale associated with campaign-based delivery can be attained, the underlying strength of the immunization program, sensitivities to the relative ease of vaccine administration (i.e. orally, or by injection), and differences in disease-specific programmatic approaches. The assessment of SIA budgets by cost component illustrates that four cost drivers make up the largest proportion of costs across all vaccines: human resources, program management, social mobilization, and vehicles and transportation. These findings suggest that SIAs leverage existing health system infrastructure, reinforcing the fact that strong routine immunization programs are an important pre-requisite for achieving ADC/E/E goals. The results presented here will be useful for national and global-level actors involved in planning, budgeting, resource mobilization, and financing of SIAs in order to create more realistic assessments of resource requirements for both existing ADC/E/E efforts as well as for new vaccines that may deploy a catch-up campaign-based delivery component. However, limitations of our analysis suggest a need to conduct further research into operational costs of SIAs. Understanding the changing face of delivery costs and cost structures for SIAs will continue to be critical to avoid funding gaps and in order to improve vaccination coverage, reduce health inequities, and achieve the ADC/E/E goals many of which have been endorsed by the World Health Assembly and are included in the Decade of Vaccines Global Vaccine Action Plan.

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.

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

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.

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.

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

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

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.

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.

TU-F-CAMPUS-I-01: Head and Neck Squamous Cell Carcinoma: Short-Term Repeatability of Apparent Diffusion Coefficient and Intravoxel Incoherent Motion Parameters at 3.0T

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

Ding, Y; Fuller, C; Mohamed, A

2015-06-15

Purpose: Many published studies have recently demonstrated the potential value of intravoxel incoherent motion (IVIM) analysis for disease evaluation. However, few have questioned its measurement repeatability/reproducibility when applied. The purpose of this study was to determine the short-term measurement repeatability of apparent diffusion coefficient ADC, true diffusion coefficient D, pseudodiffusion coefficient D* and perfusion fraction f, in head and neck squamous cell carcinoma (HNSCC) primary tumors and metastatic nodes. Methods: Ten patients with known HNSCC were examined twice using echo-planar DW-MRI with 12 b values (0 to 800 s/mm2) 1hour to 24 hours apart before radiation treatment. All patients weremore » scanned with the customized radiation treatment immobilization devices to reduce motion artifacts and to improve image registration in repeat scans. Regions of interests were drawn in primary tumor and metastases node in each patient (Fig. 1). ADC and IVIM parameters D, D* and f were calculated by least squares data fitting. Short-term test–retest repeatability of ADC and IVIM parameters were assessed by measuring Bland–Altman limits of agreements (BA-LA). Results: Sixteen HNSCC lesions were assessed in 10 patients. Repeatability of perfusion-sensitive parameters, D* and f, in HNSCC lesions was poor (BA-LA: -144% to 88% and −57% to 96% for D* and f, respectively); a lesser extent was observed for the diffusion-sensitive parameters of ADC and D (BA-LA: −34% to 39% and −37% to 40%, for ADC and D, respectively) (Fig. 2). Conclusion: Poor repeatability of D*/f and good repeatability for ADC/D were observed in HNSCC primary tumors and metastatic nodes. Efforts should be made to improve the measurement repeatability of perfusion-sensitive IVIM parameters.« less

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.

The value of whole lesion ADC histogram profiling to differentiate between morphologically indistinguishable ring enhancing lesions–comparison of glioblastomas and brain abscesses

PubMed Central

Hoffmann, Karl-Titus; Garnov, Nikita; Vörkel, Cathrin; Kohlhof-Meinecke, Patricia; Ganslandt, Oliver; Bäzner, Hansjörg; Gihr, Georg Alexander; Kalman, Marcell; Henkes, Elina; Henkes, Hans; Schob, Stefan

2018-01-01

Background Morphologically similar appearing ring enhancing lesions in the brain parenchyma can be caused by a number of distinct pathologies, however, they consistently represent life-threatening conditions. The two most frequently encountered diseases manifesting as such are glioblastoma multiforme (GBM) and brain abscess (BA), each requiring disparate therapeutical approaches. As a result of their morphological resemblance, essential treatment might be significantly delayed or even ommited, in case results of conventional imaging remain inconclusive. Therefore, our study aimed to investigate, whether ADC histogram profiling reliably can distinguish between both entities, thus enhancing the differential diagnostic process and preventing treatment failure in this highly critical context. Methods 103 patients (51 BA, 52 GBM) with histopathologically confirmed diagnosis were enrolled. Pretreatment diffusion weighted imaging (DWI) was obtained in a 1.5T system using b values of 0, 500, and 1000 s/mm2. Whole lesion ADC volumes were analyzed using a histogram-based approach. Statistical analysis was performed using SPSS version 23. Results All investigated parameters were statistically different in comparison of both groups. Most importantly, ADCp10 was able to differentiate reliably between BA and GBM with excellent accuracy (0.948) using a cutpoint value of 70 × 10−5 mm2 × s−1. Conclusions ADC whole lesion histogram profiling provides a valuable tool to differentiate between morphologically indistinguishable mass lesions. Among the investigated parameters, the 10th percentile of the ADC volume distinguished best between GBM and BA. PMID:29719596

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.

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.

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.

Photonic ADC: overcoming the bottleneck of electronic jitter.

PubMed

Khilo, Anatol; Spector, Steven J; Grein, Matthew E; Nejadmalayeri, Amir H; Holzwarth, Charles W; Sander, Michelle Y; Dahlem, Marcus S; Peng, Michael Y; Geis, Michael W; DiLello, Nicole A; Yoon, Jung U; Motamedi, Ali; Orcutt, Jason S; Wang, Jade P; Sorace-Agaskar, Cheryl M; Popović, Miloš A; Sun, Jie; Zhou, Gui-Rong; Byun, Hyunil; Chen, Jian; Hoyt, Judy L; Smith, Henry I; Ram, Rajeev J; Perrott, Michael; Lyszczarz, Theodore M; Ippen, Erich P; Kärtner, Franz X

2012-02-13

Accurate conversion of wideband multi-GHz analog signals into the digital domain has long been a target of analog-to-digital converter (ADC) developers, driven by applications in radar systems, software radio, medical imaging, and communication systems. Aperture jitter has been a major bottleneck on the way towards higher speeds and better accuracy. Photonic ADCs, which perform sampling using ultra-stable optical pulse trains generated by mode-locked lasers, have been investigated for many years as a promising approach to overcome the jitter problem and bring ADC performance to new levels. This work demonstrates that the photonic approach can deliver on its promise by digitizing a 41 GHz signal with 7.0 effective bits using a photonic ADC built from discrete components. This accuracy corresponds to a timing jitter of 15 fs - a 4-5 times improvement over the performance of the best electronic ADCs which exist today. On the way towards an integrated photonic ADC, a silicon photonic chip with core photonic components was fabricated and used to digitize a 10 GHz signal with 3.5 effective bits. In these experiments, two wavelength channels were implemented, providing the overall sampling rate of 2.1 GSa/s. To show that photonic ADCs with larger channel counts are possible, a dual 20-channel silicon filter bank has been demonstrated.

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.

[Value of 3T magnetic resonance dynamic contrast-enhanced and diffusion-weighted imaging in differential diagnosis of musculoskeletal tumors].

PubMed

Qi, Zi-hua; Li, Chuan-fu; Ma, Xiang-xing; Yang, Hui; Jiang, Bao-dong; Zhang, Kai; Yu, De-xin

2012-04-01

To evaluate the value of magnetic resonance dynamic contrast-enhanced (MR-DCE) and magnetic resonance diffusion-weighted imaging (MR-DWI) in the differentiation of benign and malignant musculoskeletal tumors. Sixty-three patients with pathologically confirmed musculoskeletal tumors were examined with MR-DCE and MR-DWI. Using single shot spin echo planar imaging sequence and different b values of 400, 600, 800 and 1000 s/mm(2), we obtained the apparent diffusion coefficient (ADC) of the lesions. ADC values were measured before and after MR-DCE, with a b value of 600 s/mm(2). The 3D fast acquired multiple phase enhanced fast spoiled gradient recalled echo sequence was obtained for multi-slice of the entire lesion. The time-signal intensity curve (TIC), dynamic contrast-enhanced parameters, maximum slope of increase (MSI), positive enhancement integral, signal enhancement ratio, and time to peak (T(peak)) were also recorded. ADC showed no significant difference between benign and malignant tumors when the b value was 400, 600, 800, or 1000 s/mm(2), and it was not significantly different between benign and malignant tumors in both pre-MR-DCE and post-MR-DCE with b value of 600 s/mm(2). TIC were classified into four types type1 showed rapid progression and gradual drainage; type2 showed rapid progression but had no or slight progression; type 3 showed gradual progression; and type 4 had no or slight progression. Most lesions of type1 or type2 were malignant, whereas most lesions of type 3 or type 4 were benign. When using type1 and type 2 as the standards of malignancy, the diagnostic sensitivity and specificity was 87.23% and 50.00%, respectively. The types of TIC showed significant difference between benign and malignant musculoskeletal tumors(χ(2)=17.009,P=0.001). When using MSI 366.62 ± 174.84 as the standard of malignancy, the diagnostic sensitivity and specificity was 86.78% and 78.67%, respectively. When using T(peak)≤70s as the standard of malignancy, the diagnostic sensitivity and specificity was 82.89%and 85.78%, respectively. Positive enhancement integral and signal enhancement ratio showed no significant difference between benign and malignant musculoskeletal tumors. TIC, MSI and T(peak) of MR-DCE are valuable in differentiating benign from malignant musculoskeletal tumors. T(peak) has the highest diagnostic specificity, and TIC has the highest diagnostic sensitivity. The mean ADC value are no significant difference between benign and malignant tumors.

[Correlation between the mRNA expression of tissue inhibitor of metalloproteinase-1 and apparent diffusion coefficient on diffusion-weighted imaging in rats' liver fibrosis].

PubMed

Zhan, Yuefu; Liang, Xianwen; Han, Xiangjun; Chen, Jianqiang; Zhang, Shufang; Tan, Shun; Li, Qun; Wang, Xiong; Liu, Fan

2017-02-28

To explore the correlation between the apparent diffusion coefficient (ADC) and mRNA expression of tissue inhibitor of metalloproteinase-1 (TIMP-1) in different stages of liver fibrosis in rats.
 Methods: A model of liver fibrosis in rats was established by intraperitoneal injection of high-fat diet combined with porcine serum. After drug administration for 4 weeks, 48 rats served as a model group and 12 rats served as a control group, then they underwent diffusion weighted imaging (DWI) scanning. The value of ADC was calculated at b value=800 s/mm2. The rats were sacrificed and carried out pathologic examination after DWI scanning immediately. The mRNA expression of TIMP-1 was detected by real time-polymerase chain reaction (RT-PCR). The rats of hepatic fibrosis were also divided into a S0 group (n=4), a S1 group (n=11), a S2 group (n=12), a S3 group (n=10), and a S4 group (n=9) according to their pathological stage. The value of ADC and the expression of TIMP-1 mRNA among the different stage groups of liver fibrosis were compared, and the correlation between ADC and the TIMP-1 mRNA were analyzed.
 Results: The ADC value and the TIMP-1 mRNA expression were significantly different between the control group and the liver fibrosis group (F=46.54 and 53.87, P<0.05). There were significant differences in the value of ADC between every two groups (all P<0.05), except the control group vs the S1 group, the S1 group vs the S2 group, and the S2 group vs the S3 group (all P>0.05). For the comparison of TIMP-1 mRNA, there was no significant difference between the S1 group and the S2 group, the S3 group and the S4 group (both P>0.05). There were significant differences among the rest of the groups (all P<0.05). Rank correlation analysis showed that there was a negative correlation between the ADC value and the TIMP-1 mRNA expression (r=-0.76, P<0.01).
 Conclusion: When the value of ADC decreases in the progress of rats' liver fibrosis, the mRNA expression of TIMP-1 increases gradually, and there is a negative correlation between them.

The Development and Standardization of the Adult Developmental Co-Ordination Disorders/Dyspraxia Checklist (ADC)

ERIC Educational Resources Information Center

Kirby, Amanda; Edwards, Lisa; Sugden, David; Rosenblum, Sara

2010-01-01

Developmental Co-ordination Disorder (DCD), also known as Dyspraxia in the United Kingdom (U.K.), is a developmental disorder affecting motor co-ordination. In the past this was regarded as a childhood disorder, however there is increasing evidence that a significant number of children will continue to have persistent difficulties into adulthood.…

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

Diffusion profiling of tumor volumes using a histogram approach can predict proliferation and further microarchitectural features in medulloblastoma.

PubMed

Schob, Stefan; Beeskow, Anne; Dieckow, Julia; Meyer, Hans-Jonas; Krause, Matthias; Frydrychowicz, Clara; Hirsch, Franz-Wolfgang; Surov, Alexey

2018-05-31

Medulloblastomas are the most common central nervous system tumors in childhood. Treatment and prognosis strongly depend on histology and transcriptomic profiling. However, the proliferative potential also has prognostical value. Our study aimed to investigate correlations between histogram profiling of diffusion-weighted images and further microarchitectural features. Seven patients (age median 14.6 years, minimum 2 years, maximum 20 years; 5 male, 2 female) were included in this retrospective study. Using a Matlab-based analysis tool, histogram analysis of whole apparent diffusion coefficient (ADC) volumes was performed. ADC entropy revealed a strong inverse correlation with the expression of the proliferation marker Ki67 (r = - 0.962, p = 0.009) and with total nuclear area (r = - 0.888, p = 0.044). Furthermore, ADC percentiles, most of all ADCp90, showed significant correlations with Ki67 expression (r = 0.902, p = 0.036). Diffusion histogram profiling of medulloblastomas provides valuable in vivo information which potentially can be used for risk stratification and prognostication. First of all, entropy revealed to be the most promising imaging biomarker. However, further studies are warranted.

Demonstration of Nonlinearity Bias in the Measurement of the Apparent Diffusion Coefficient in Multicenter Trials

PubMed Central

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

2015-01-01

Purpose Characterize system-specific bias across common magnetic resonance imaging (MRI) platforms for quantitative diffusion measurements in multicenter trials. Methods Diffusion weighted imaging (DWI) was performed on an ice-water phantom along the superior-inferior (SI) and right-left (RL) orientations spanning ±150 mm. The same scanning protocol was implemented on 14 MRI systems at seven imaging centers. The bias was estimated as a deviation of measured from known apparent diffusion coefficient (ADC) along individual DWI directions. The relative contributions of gradient nonlinearity, shim errors, imaging gradients and eddy currents were assessed independently. The observed bias errors were compared to numerical models. Results The measured systematic ADC errors scaled quadratically with offset from isocenter, and ranged between −55% (SI) and 25% (RL). Nonlinearity bias was dependent on system design and diffusion gradient direction. Consistent with numerical models, minor ADC errors (±5%) due to shim, imaging and eddy currents were mitigated by double echo DWI and image co-registration of individual gradient directions. Conclusion The analysis confirms gradient nonlinearity as a major source of spatial DW bias and variability in off-center ADC measurements across MRI platforms, with minor contributions from shim, imaging gradients and eddy currents. The developed protocol enables empiric description of systematic bias in multicenter quantitative DWI studies. PMID:25940607

Demonstration of nonlinearity bias in the measurement of the apparent diffusion coefficient in multicenter trials.

PubMed

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

2016-03-01

Characterize system-specific bias across common magnetic resonance imaging (MRI) platforms for quantitative diffusion measurements in multicenter trials. Diffusion weighted imaging (DWI) was performed on an ice-water phantom along the superior-inferior (SI) and right-left (RL) orientations spanning ± 150 mm. The same scanning protocol was implemented on 14 MRI systems at seven imaging centers. The bias was estimated as a deviation of measured from known apparent diffusion coefficient (ADC) along individual DWI directions. The relative contributions of gradient nonlinearity, shim errors, imaging gradients, and eddy currents were assessed independently. The observed bias errors were compared with numerical models. The measured systematic ADC errors scaled quadratically with offset from isocenter, and ranged between -55% (SI) and 25% (RL). Nonlinearity bias was dependent on system design and diffusion gradient direction. Consistent with numerical models, minor ADC errors (± 5%) due to shim, imaging and eddy currents were mitigated by double echo DWI and image coregistration of individual gradient directions. The analysis confirms gradient nonlinearity as a major source of spatial DW bias and variability in off-center ADC measurements across MRI platforms, with minor contributions from shim, imaging gradients and eddy currents. The developed protocol enables empiric description of systematic bias in multicenter quantitative DWI studies. © 2015 Wiley Periodicals, Inc.

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.

Cancer incidence and mortality for all causes in HIV-infected patients over a quarter century: a multicentre cohort study.

PubMed

Raffetti, Elena; Albini, Laura; Gotti, Daria; Segala, Daniela; Maggiolo, Franco; di Filippo, Elisa; Saracino, Annalisa; Ladisa, Nicoletta; Lapadula, Giuseppe; Fornabaio, Chiara; Castelnuovo, Filippo; Casari, Salvatore; Fabbiani, Massimiliano; Pierotti, Piera; Donato, Francesco; Quiros-Roldan, Eugenia

2015-03-12

We aimed to assess cancer incidence and mortality for all-causes and factors related to risk of death in an Italian cohort of HIV infected unselected patients as compared to the general population. We conducted a retrospective (1986-2012) cohort study on 16 268 HIV infected patients enrolled in the MASTER cohort. The standardized incidence ratios (SIRs) and standardized mortality ratios (SMRs) were computed using cancer incidence rates of Italian Cancer Registries and official national data for overall mortality. The risk factors for death from all causes were assessed using Poisson regression models. 1,195 cancer cases were diagnosed from 1986 to 2012: 700 AIDS-defining-cancers (ADCs) and 495 non-AIDS-defining-cancers (NADCs). ADC incidence was much higher than the Italian population (SIR = 30.8, 95% confidence interval 27.9-34.0) whereas NADC incidence was similar to the general population (SIR = 0.9, 95% CI 0.8-1.1). The SMR for all causes was 11.6 (11.1-12.0) in the period, and it decreased over time, mainly after 1996, up to 3.53 (2.5-4.8) in 2012. Male gender, year of enrolment before 1993, older age at enrolment, intravenous drug use, low CD4 cell count, AIDS event, cancer occurrence and the absence of antiretroviral therapy were all associated independently with risk of death. In HIV infected patients, ADC but not NADC incidence rates were higher than the general population. Although overall mortality in HIV infected subjects decreased over time, it is about three-fold higher than the general population at present.

107 Gb/s coherent optical OFDM transmission over 1000-km SSMF fiber using orthogonal band multiplexing.

PubMed

Shieh, W; Yang, Q; Ma, Y

2008-04-28

Coherent optical OFDM (CO-OFDM) has emerged as an attractive modulation format for the forthcoming 100 Gb/s Ethernet. However, even the spectral-efficient implementation of CO-OFDM requires digital-to-analog converters (DAC) and analog-to-digital converters (ADC) to operate at the bandwidth which may not be available today or may not be cost-effective. In order to resolve the electronic bandwidth bottleneck associated with DAC/ADC devices, we propose and elucidate the principle of orthogonal-band-multiplexed OFDM (OBM-OFDM) to subdivide the entire OFDM spectrum into multiple orthogonal bands. With this scheme, the DAC/ADCs do not need to operate at extremely high sampling rate. The corresponding mapping to the mixed-signal integrated circuit (IC) design is also revealed. Additionally, we show the proof-of-concept transmission experiment through optical realization of OBM-OFDM. To the best of our knowledge, we present the first experimental demonstration of 107 Gb/s QPSK-encoded CO-OFDM signal transmission over 1000 km standard-single- mode-fiber (SSMF) without optical dispersion compensation and without Raman amplification. The demonstrated system employs 2x2 MIMO-OFDM signal processing and achieves high electrical spectral efficiency with direct-conversion at both transmitter and receiver.

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.

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.

Correlation of the apparent diffusion coefficient and the standardized uptake value in neoplastic lesions: a meta-analysis.

PubMed

Shen, Guohua; Ma, Huan; Liu, Bin; Ren, Pengwei; Kuang, Anren

2017-12-01

Diffusion-weighted imaging and fluorine-18-fluorodeoxyglucose PET are increasingly being recognized as feasible oncological techniques. The apparent diffusion coefficient (ADC) measured by diffusion-weighted imaging and the standardized uptake value (SUV) from fluorine-18-fluorodeoxyglucose PET have similar clinical applications. The aim of this study was to assess the correlation between these two parameters in various cancers. Several major databases were searched for eligible studies. The correlation coefficient (ρ) values were pooled in a random-effects model. Begg's test was used to analyze the existence of publication bias and the sources of heterogeneity were explored in subgroup analyses on the basis of study design, diagnostic method, scanning modality, and tumor type. Thirty-five articles were accepted. The pooled ρ value of all of the accepted studies was -0.30 (95% confidence interval: -0.33 to -0.27), and notable heterogeneity was present (I=69.4%, P<0.001), which indicated a relatively weak negative correlation. The pooled ρ values were -0.26, -0.33, -0.32, and -0.33 for the SUVmax/ADCmean, SUVmax/ADCmin, SUVmean/ADCmean, and SUVmean/ADCmin relationships, respectively. The study design and diagnostic method were potential sources of heterogeneity. Lung cancer showed a stronger correlation (ρ=-0.42) than head and neck cancer (ρ=-0.27), cervical cancer (ρ=-0.21), and breast cancer (ρ=-0.23). A Begg's test indicated no significant publication bias among the accepted studies (P>0.05). The two functional parameters of ADC and SUV showed a very weak inverse correlation, which may contribute toward a sophisticated characterization of tumor biology. However, the findings require further validation with trials with large samples and different tumor types.

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.

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.

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.

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.

Nuclear Overhauser Enhancement Imaging of Glioblastoma at 7 Tesla: Region Specific Correlation with Apparent Diffusion Coefficient and Histology

PubMed Central

Windschuh, Johannes; Meissner, Jan-Eric; Zaiss, Moritz; Eidel, Oliver; Kickingereder, Philipp; Nowosielski, Martha; Wiestler, Benedikt; Sahm, Felix; Floca, Ralf Omar; Neumann, Jan-Oliver; Wick, Wolfgang; Heiland, Sabine; Bendszus, Martin; Schlemmer, Heinz-Peter; Ladd, Mark Edward; Bachert, Peter; Radbruch, Alexander

2015-01-01

Objective To explore the correlation between Nuclear Overhauser Enhancement (NOE)-mediated signals and tumor cellularity in glioblastoma utilizing the apparent diffusion coefficient (ADC) and cell density from histologic specimens. NOE is one type of chemical exchange saturation transfer (CEST) that originates from mobile macromolecules such as proteins and might be associated with tumor cellularity via altered protein synthesis in proliferating cells. Patients and Methods For 15 patients with newly diagnosed glioblastoma, NOE-mediated CEST-contrast was acquired at 7 Tesla (asymmetric magnetization transfer ratio (MTRasym) at 3.3ppm, B1 = 0.7 μT). Contrast enhanced T1 (CE-T1), T2 and diffusion-weighted MRI (DWI) were acquired at 3 Tesla and coregistered. The T2 edema and the CE-T1 tumor were segmented. ADC and MTRasym values within both regions of interest were correlated voxelwise yielding the correlation coefficient rSpearman (rSp). In three patients who underwent stereotactic biopsy, cell density of 12 specimens per patient was correlated with corresponding MTRasym and ADC values of the biopsy site. Results Eight of 15 patients showed a weak or moderate positive correlation of MTRasym and ADC within the T2 edema (0.16≤rSp≤0.53, p<0.05). Seven correlations were statistically insignificant (p>0.05, n = 4) or yielded rSp≈0 (p<0.05, n = 3). No trend towards a correlation between MTRasym and ADC was found in CE-T1 tumor (-0.310.05, n = 6). The biopsy-analysis within CE-T1 tumor revealed a strong positive correlation between tumor cellularity and MTRasym values in two of the three patients (rSp patient3 = 0.69 and rSp patient15 = 0.87, p<0.05), while the correlation of ADC and cellularity was heterogeneous (rSp patient3 = 0.545 (p = 0.067), rSp patient4 = -0.021 (p = 0.948), rSp patient15 = -0.755 (p = 0.005)). Discussion NOE-imaging is a new contrast promising insight into pathophysiologic processes in glioblastoma regarding cell density and protein content, setting itself apart from DWI. Future studies might be based on the assumption that NOE-mediated CEST visualizes cellularity more accurately than ADC, especially in the CE-T1 tumor region. PMID:25789657

Nuclear Overhauser Enhancement imaging of glioblastoma at 7 Tesla: region specific correlation with apparent diffusion coefficient and histology.

PubMed

Paech, Daniel; Burth, Sina; Windschuh, Johannes; Meissner, Jan-Eric; Zaiss, Moritz; Eidel, Oliver; Kickingereder, Philipp; Nowosielski, Martha; Wiestler, Benedikt; Sahm, Felix; Floca, Ralf Omar; Neumann, Jan-Oliver; Wick, Wolfgang; Heiland, Sabine; Bendszus, Martin; Schlemmer, Heinz-Peter; Ladd, Mark Edward; Bachert, Peter; Radbruch, Alexander

2015-01-01

To explore the correlation between Nuclear Overhauser Enhancement (NOE)-mediated signals and tumor cellularity in glioblastoma utilizing the apparent diffusion coefficient (ADC) and cell density from histologic specimens. NOE is one type of chemical exchange saturation transfer (CEST) that originates from mobile macromolecules such as proteins and might be associated with tumor cellularity via altered protein synthesis in proliferating cells. For 15 patients with newly diagnosed glioblastoma, NOE-mediated CEST-contrast was acquired at 7 Tesla (asymmetric magnetization transfer ratio (MTRasym) at 3.3ppm, B1 = 0.7 μT). Contrast enhanced T1 (CE-T1), T2 and diffusion-weighted MRI (DWI) were acquired at 3 Tesla and coregistered. The T2 edema and the CE-T1 tumor were segmented. ADC and MTRasym values within both regions of interest were correlated voxelwise yielding the correlation coefficient rSpearman (rSp). In three patients who underwent stereotactic biopsy, cell density of 12 specimens per patient was correlated with corresponding MTRasym and ADC values of the biopsy site. Eight of 15 patients showed a weak or moderate positive correlation of MTRasym and ADC within the T2 edema (0.16≤rSp≤0.53, p<0.05). Seven correlations were statistically insignificant (p>0.05, n = 4) or yielded rSp≈0 (p<0.05, n = 3). No trend towards a correlation between MTRasym and ADC was found in CE-T1 tumor (-0.310.05, n = 6). The biopsy-analysis within CE-T1 tumor revealed a strong positive correlation between tumor cellularity and MTRasym values in two of the three patients (rSppatient3 = 0.69 and rSppatient15 = 0.87, p<0.05), while the correlation of ADC and cellularity was heterogeneous (rSppatient3 = 0.545 (p = 0.067), rSppatient4 = -0.021 (p = 0.948), rSppatient15 = -0.755 (p = 0.005)). NOE-imaging is a new contrast promising insight into pathophysiologic processes in glioblastoma regarding cell density and protein content, setting itself apart from DWI. Future studies might be based on the assumption that NOE-mediated CEST visualizes cellularity more accurately than ADC, especially in the CE-T1 tumor region.

Evaluation of normal appearing spinal cord by diffusion tensor imaging, fiber tracking, fractional anisotropy, and apparent diffusion coefficient measurement in 13 dogs

PubMed Central

2013-01-01

Background Functional magnetic resonance (fMR) imaging offers plenty of new opportunities in the diagnosis of central nervous system diseases. Diffusion tensor imaging (DTI) is a technique sensitive to the random motion of water providing information about tissue architecture. We applied DTI to normal appearing spinal cords of 13 dogs of different breeds and body weights in a 3.0 T magnetic resonance (MR) scanner. The aim was to study fiber tracking (FT) patterns by tractography and the variations of the fractional anisotropy (FA) and the apparent diffusion coefficient (ADC) observed in the spinal cords of dogs with different sizes and at different locations (cervical and thoracolumbar). For that reason we added a DTI sequence to the standard clinical MR protocol. The values of FA and ADC were calculated by means of three regions of interest defined on the cervical or the thoracolumbar spinal cord (ROI 1, 2, and 3). Results The shape of the spinal cord fiber tracts was well illustrated following tractography and the exiting nerve roots could be differentiated from the spinal cord fiber tracts. Routine MR scanning times were extended for 8 to 12 min, depending on the size of the field of view (FOV), the slice thickness, and the size of the interslice gaps. In small breed dogs (< 15 kg body weight) the fibers could be tracked over a length of approximately 10 vertebral bodies with scanning times of about 8 min, whereas in large breed dogs (> 25 kg body weight) the traceable fiber length was about 5 vertebral bodies which took 10 to 12 min scanning time. FA and ADC values showed mean values of 0.447 (FA), and 0.560 × 10-3 mm2/s (ADC), respectively without any differences detected with regard to different dog sizes and spinal cord 45 segments examined. Conclusion FT is suitable for the graphical depiction of the canine spinal cord and the exiting nerve roots. The FA and ADC values offer an objective measure for evaluation of the spinal cord fiber integrity in dogs. PMID:23618404

SU-F-T-157: Physics Considerations Regarding Dosimetric Accuracy of Analytical Dose Calculations for Small Field Proton Therapy: A Monte Carlo Study

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

Geng, C; Nanjing University of Aeronautics and Astronautics, Nanjing; Daartz, J

Purpose: To evaluate the accuracy of dose calculations by analytical dose calculation methods (ADC) for small field proton therapy in a gantry based passive scattering facility. Methods: 50 patients with intra-cranial disease were evaluated in the study. Treatment plans followed standard prescription and optimization procedures of proton stereotactic radiosurgery. Dose distributions calculated with the Monte Carlo (MC) toolkit TOPAS were used to represent delivered treatments. The MC dose was first adjusted using the output factor (OF) applied clinically. This factor is determined from the field size and the prescribed range. We then introduced a normalization factor to measure the differencemore » in mean dose between the delivered dose (MC dose with OF) and the dose calculated by ADC for each beam. The normalization was determined by the mean dose of the center voxels of the target area. We compared delivered dose distributions and those calculated by ADC in terms of dose volume histogram parameters and beam range distributions. Results: The mean target dose for a whole treatment is generally within 5% comparing delivered dose (MC dose with OF) and ADC dose. However, the differences can be as great as 11% for shallow and small target treated with a thick range compensator. Applying the normalization factor to the MC dose with OF can reduce the mean dose difference to less than 3%. Considering range uncertainties, the generally applied margins (3.5% of the prescribed range + 1mm) to cover uncertainties in range might not be sufficient to guarantee tumor coverage. The range difference for R90 (90% distal dose falloff) is affected by multiple factors, such as the heterogeneity index. Conclusion: This study indicates insufficient accuracy calculating proton doses using ADC. Our results suggest that uncertainties of target doses are reduced using MC techniques, improving the dosimetric accuracy for proton stereotactic radiosurgery. The work was supported by NIH/NCI under CA U19 021239. CG was partially supported by the Chinese Scholarship Council (CSC) and the National Natural Science Foundation of China (Grant No. 11475087).« less

Investigation of compression behavior of PE/EVA foam injection molded parts

NASA Astrophysics Data System (ADS)

Spina, Roberto

2017-10-01

The main objective of the presented work is to evaluate the compression behavior of a polymeric foam blend by using a robust framework for the testing sequence of foaming injection molded parts, with the aim of establishing a standard testing cycle for the evaluation of new matrix material. The research purpose is to assess parameters influencing compression behavior and give useful suggestions for the implementation of a finite element analysis. The polymeric blend consisted of a mixture of low density polyethylenes (LDPEs), a high-density polyethylene (HDPE), an ethylene-vinyl acetate (EVA) and an azodicarbonamide (ADC). The thermal, rheological and compression properties of the blend are fully described, as well as the injection molding process for two specimen types.

Numerical-experimental investigation of PE/EVA foam injection molded parts

NASA Astrophysics Data System (ADS)

Spina, Roberto

The main objective of the presented work is to propose a robust framework to test foaming injection molded parts, with the aim of establishing a standard testing cycle for the evaluation of a new foam material based on numerical and experimental results. The research purpose is to assess parameters influencing several aspects, such as foam morphology and compression behavior, using useful suggestions from finite element analysis. The investigated polymeric blend consisted of a mixture of low density polyethylenes (LDPEs), a high-density polyethylene (HDPE), an ethylene-vinyl acetate (EVA) and an azodicarbonamide (ADC). The thermal, rheological and compression properties of the blend are fully described, as well as the numerical models and the parameters of the injection molding process.

Liver fibrosis: in vivo evaluation using intravoxel incoherent motion-derived histogram metrics with histopathologic findings at 3.0 T.

PubMed

Hu, Fubi; Yang, Ru; Huang, Zixing; Wang, Min; Zhang, Hanmei; Yan, Xu; Song, Bin

2017-12-01

To retrospectively determine the feasibility of intravoxel incoherent motion (IVIM) imaging based on histogram analysis for the staging of liver fibrosis (LF) using histopathologic findings as the reference standard. 56 consecutive patients (14 men, 42 women; age range, 15-76, years) with chronic liver diseases (CLDs) were studied using IVIM-DWI with 9 b-values (0, 25, 50, 75, 100, 150, 200, 500, 800 s/mm 2 ) at 3.0 T. Fibrosis stage was evaluated using the METAVIR scoring system. Histogram metrics including mean, standard deviation (Std), skewness, kurtosis, minimum (Min), maximum (Max), range, interquartile (Iq) range, and percentiles (10, 25, 50, 75, 90th) were extracted from apparent diffusion coefficient (ADC), true diffusion coefficient (D), pseudo-diffusion coefficient (D*), and perfusion fraction (f) maps. All histogram metrics among different fibrosis groups were compared using one-way analysis of variance or nonparametric Kruskal-Wallis test. For significant parameters, receivers operating characteristic curve (ROC) analyses were further performed for the staging of LF. Based on their METAVIR stage, the 56 patients were reclassified into three groups as follows: F0-1 group (n = 25), F2-3 group (n = 21), and F4 group (n = 10). The mean, Iq range, percentiles (50, 75, and 90th) of D* maps between the groups were significant differences (all P < 0.05). Area under the ROC curve (AUC) of the mean, Iq range, 50, 75, and 90th percentile of D* maps for identifying significant LF (≥F2 stage) was 0.901, 0.859, 0.876, 0.943, and 0.886 (all P < 0.0001), respectively; for diagnosing severe fibrosis or cirrhosis (F4), AUC was 0.917, 0.922, 0.943, 0.985, and 0.939 (all P < 0.0001), respectively. The histogram metrics of ADC, D, and f maps demonstrated no significant difference among the groups (all P > 0.05). Histogram analysis of D* map derived from IVIM can be used to stage liver fibrosis in patients with CLDs and provide more quantitative information beyond the mean value.

[Optimization of diagnosis indicator selection and inspection plan by 3.0T MRI in breast cancer].

PubMed

Jiang, Zhongbiao; Wang, Yunhua; He, Zhong; Zhang, Lejun; Zheng, Kai

2013-08-01

To optimize 3.0T MRI diagnosis indicator in breast cancer and to select the best MRI scan program. Totally 45 patients with breast cancers were collected, and another 35 patients with benign breast tumor served as the control group. All patients underwent 3.0T MRI, including T1- weighted imaging (T1WI), fat suppression of the T2-weighted imaging (T2WI), diffusion weighted imaging (DWI), 1H magnetic resonance spectroscopy (1H-MRS) and dynamic contrast enhanced (DCE) sequence. With operation pathology results as the gold standard in the diagnosis of breast diseases, the pathological results of benign and malignant served as dependent variables, and the diagnostic indicators of MRI were taken as independent variables. We put all the indicators of MRI examination under Logistic regression analysis, established the Logistic model, and optimized the diagnosis indicators of MRI examination to further improve MRI scan of breast cancer. By Logistic regression analysis, some indicators were selected in the equation, including the edge feature of the tumor, the time-signal intensity curve (TIC) type and the apparent diffusion coefficient (ADC) value when b=500 s/mm2. The regression equation was Logit (P)=-21.936+20.478X6+3.267X7+ 21.488X3. Valuable indicators in the diagnosis of breast cancer are the edge feature of the tumor, the TIC type and the ADC value when b=500 s/mm2. Combining conventional MRI scan, DWI and dynamic enhanced MRI is a better examination program, while MRS is the complementary program when diagnosis is difficult.

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.

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

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.

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.

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

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.

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

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.

Quantitative Magnetic Resonance Diffusion-Weighted Imaging Evaluation of the Supratentorial Brain Regions in Patients Diagnosed with Brainstem Variant of Posterior Reversible Encephalopathy Syndrome: A Preliminary Study.

PubMed

Chen, Tai-Yuan; Wu, Te-Chang; Ko, Ching-Chung; Feng, I-Jung; Tsui, Yu-Kun; Lin, Chien-Jen; Chen, Jeon-Hor; Lin, Ching-Po

2017-07-01

Posterior reversible encephalopathy syndrome (PRES) is a clinicoradiologic entity with several causes, characterized by rapid onset of symptoms and typical neuroimaging features, which usually resolve if promptly recognized and treated. Brainstem variant of PRES presents with vasogenic edema in brainstem regions on magnetic resonance (MR) images and there is sparing of the supratentorial regions. Because PRES is usually caused by a hypertensive crisis, which would likely have a systemic effect and global manifestations on the brain tissue, we thus proposed that some microscopic abnormalities of the supratentorial regions could be detected with diffusion-weighted imaging (DWI) using apparent diffusion coefficient (ADC) analysis in brainstem variant of PRES and hypothesized that "normal-looking" supratentorial regions will increase water diffusion. We retrospectively identified patients with PRES who underwent brain magnetic resonance imaging studies. We identified 11 brainstem variants of PRES patients, who formed the study cohort, and 11 typical PRES patients and 20 normal control subjects as the comparison cohorts for this study. Nineteen regions of interest were drawn and systematically placed. The mean ADC values were measured and compared among these 3 groups. ADC values of the typical PRES group were consistently elevated compared with those in normal control subjects. ADC values of the brainstem variant group were consistently elevated compared with those in normal control subjects. ADC values of the typical PRES group and brainstem variant group did not differ significantly, except for the pons area. Quantitative MR DWI may aid in the evaluation of supratentorial microscopic abnormalities in brainstem variant of PRES patients. Copyright © 2017 National Stroke Association. Published by Elsevier Inc. 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.

Diffusion-weighted magnetic resonance imaging to differentiate malignant from benign gallbladder disorders.

PubMed

Kitazume, Yoshio; Taura, Shin-Ichi; Nakaminato, Shuichiro; Noguchi, Osamu; Masaki, Yukiyoshi; Kasahara, Ichiro; Kishino, Mitsuhiro; Tateishi, Ukihide

2016-04-01

To retrospectively evaluate the utility of apparent diffusion coefficient (ADC) and lesion to spinal cord ratio (LSR) in diffusion-weighted magnetic resonance (MR) imaging (DWI) as compared with morphological assessment alone, for differentiating malignant from benign gallbladder disorders. This study was approved by the ethics committee, and written informed consent was waived. Ninety-one patients (13 malignancy and 78 benignancy) were reviewed. ADC was calculated using two DW images with different motion-probing gradient strengths (b=0, 1000s/mm(2)). LSR was measured by dividing the signal intensity of a thickened gallbladder wall by the maximum signal intensity of the lumbar enlargement of the spinal cord. In addition, the morphology of the gallbladders was assessed with conventional MR imaging. In receiver operating characteristic curve analysis, the areas under the curves for ADC and LSR were 0.861 and 0.906, respectively. Three morphological findings were considered: a massive formation, a disrupted mucosal line, and the absence of a two-layered pattern. When a combination of two or more of these morphological findings was positive for malignancy, the sensitivity, specificity, and accuracy were 76.9%, 84.0%, and 83.0%, respectively. When a combination of three or more of the above morphological findings together with ADC of less than 1.2 × 10(-3)mm(2)/s or LSR of more than 0.48 were positive for malignancy, these values were 73.0%, 96.2%, and 92.9%, respectively. There were significant differences in specificity and accuracy. Use of ADC and LSR in DWI can improve diagnostic performance for differentiating malignant from benign gallbladder disorders. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Osteosarcoma subtypes: Magnetic resonance and quantitative diffusion weighted imaging criteria.

PubMed

Zeitoun, Rania; Shokry, Ahmed M; Ahmed Khaleel, Sahar; Mogahed, Shaimaa M

2018-03-01

Osteosarcoma (OS) is a primary bone malignancy, characterized by spindle cells producing osteoid. The objective of this study is to describe the magnetic resonance imaging (MRI) features of different OS subtypes, record their attenuation diffusion coefficient (ADC) values and to point to the relation of their pathologic base and their corresponding ADC value. We performed a retrospective observational lesion-based analysis for 31 pathologically proven osteosarcoma subtypes: osteoblastic (n = 9), fibroblastic (n = 8), chondroblastic (n = 6), para-osteal (n = 3), periosteal (n = 1), telangiectatic (n = 2), small cell (n = 1) and extra-skeletal (n = 1). On conventional images we recorded: bone of origin, epicenter, intra-articular extension, and invasion of articulating bones, skip lesions, distant metastases, pathological fractures, ossified matrix, hemorrhage and necrosis. We measured the mean ADC value for each lesion. Among the included OS lesions, 51.6% originated at the femur, 29% showed intra-articular extension, 16% invaded neighboring bone, 9% were associated with pathological fracture and 25.8% were associated with distant metastases. On MRI, all lesions showed ossified matrix, 35.5% showed hemorrhage and 58% showed necrosis. The mean ADC values for OS lesions ranged from 0.74 × 10 -3  mm 2 /s (recorded for conventional osteoblastic OS) to 1.50 × 10 -3  mm 2 /s (recorded for telangiectatic OS) with an average value of 1.16 ± 0.18 × 10 -3  mm 2 /s. Conventional chondroblastic OS recorded higher values compared to the other two conventional subtypes. Osteosarcoma has different pathologic subtypes which correspondingly vary in their imaging criteria and their ADC values. Copyright © 2018. Production and hosting by Elsevier B.V.

Apparent Diffusion Coefficient Value Changes and Clinical Correlation in 90 Cases of Cytomegalovirus-Infected Fetuses with Unremarkable Fetal MRI Results.

PubMed

Kotovich, D; Guedalia, J S B; Hoffmann, C; Sze, G; Eisenkraft, A; Yaniv, G

2017-07-01

Cytomegalovirus is the leading intrauterine infection. Fetal MR imaging is an accepted tool for fetal brain evaluation, yet it still lacks the ability to accurately predict the extent of the neurodevelopmental impairment, especially in fetal MR imaging scans with unremarkable findings. Our hypothesis was that intrauterine cytomegalovirus infection causes diffusional changes in fetal brains and that those changes may correlate with the severity of neurodevelopmental deficiencies. A retrospective analysis was performed on 90 fetal MR imaging scans of cytomegalovirus-infected fetuses with unremarkable results and compared with a matched gestational age control group of 68 fetal head MR imaging scans. ADC values were measured and averaged in the frontal, parietal, occipital, and temporal lobes; basal ganglia; thalamus; and pons. For neurocognitive assessment, the Vineland Adaptive Behavior Scales, Second Edition (VABS-II) was used on 58 children in the cytomegalovirus-infected group. ADC values were reduced for the cytomegalovirus-infected fetuses in most brain areas studied. The VABS-II showed no trend for the major domains or the composite score of the VABS-II for the cytomegalovirus-infected children compared with the healthy population distribution. Some subdomains showed an association between ADC values and VABS-II scores. Cytomegalovirus infection causes diffuse reduction in ADC values in the fetal brain even in unremarkable fetal MR imaging scans. Cytomegalovirus-infected children with unremarkable fetal MR imaging scans do not deviate from the healthy population in the VABS-II neurocognitive assessment. ADC values were not correlated with VABS-II scores. However, the lack of clinical findings, as seen in most cytomegalovirus-infected fetuses, does not eliminate the possibility of future neurodevelopmental pathology. © 2017 by American Journal of Neuroradiology.

Brentuximab vedotin, an antibody–drug conjugate, in patients with CD30‐positive haematologic malignancies and hepatic or renal impairment

PubMed Central

Chen, Robert; O'Connor, Owen A.; Gopal, Ajay K.; Ramchandren, Radhakrishnan; Goy, Andre; Matous, Jeffrey V.; Fasanmade, Adedigbo A.; Manley, Thomas J.; Han, Tae H.

2016-01-01

Abstract Aims Brentuximab vedotin, an antibody–drug conjugate (ADC), selectively delivers the microtubule‐disrupting agent monomethyl auristatin E (MMAE) into CD30‐expressing cells. The pharmacokinetics of brentuximab vedotin have been characterized in patients with CD30‐positive haematologic malignancies. The primary objective of this phase 1 open label evaluation was to assess the pharmacokinetics of brentuximab vedotin in patients with hepatic or renal impairment. Methods Systemic exposures were evaluated following intravenous administration of 1.2 mg kg–1 brentuximab vedotin in patients with CD30‐positive haematologic malignancies and hepatic (n = 7) or renal (n = 10) impairment and compared with those of unimpaired patients (n = 8) who received 1.2 mg kg–1 brentuximab vedotin in another arm of the study. Results For any hepatic impairment, the ratios of geometric means (90% confidence interval) for AUC(0,∞) were 0.67 (0.48, 0.93) for ADC and 2.29 (1.27, 4.12) for MMAE. Mild or moderate renal impairment caused no apparent change in ADC or MMAE exposures. Severe renal impairment (creatinine clearance <30 ml min–1; n = 3) decreased ADC exposures (0.71 [0.54, 0.94]) and increased MMAE exposures (1.90 [0.85, 4.21]). No consistent pattern of specific adverse events was evident, but analysis of the safety data was confounded by the patients' poor baseline conditions. Five patients died due to adverse events considered unrelated to brentuximab vedotin. All had substantial comorbidities and most had poor baseline performance status. Conclusions Hepatic impairment and severe renal impairment may cause decreases in brentuximab vedotin ADC exposures and increases in MMAE exposures. PMID:27115790

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.

Survival after cancer diagnosis in a cohort of HIV-positive individuals in Latin America.

PubMed

Fink, Valeria I; Jenkins, Cathy A; Castilho, Jessica L; Person, Anna K; Shepherd, Bryan E; Grinsztejn, Beatriz; Netto, Juliana; Crabtree-Ramirez, Brenda; Cortés, Claudia P; Padgett, Denis; Jayathilake, Karu; McGowan, Catherine; Cahn, Pedro

2018-01-01

This study aimed to evaluate trends and predictors of survival after cancer diagnosis in persons living with HIV in the Caribbean, Central, and South America network for HIV epidemiology cohort. Demographic, cancer, and HIV-related data from HIV-positive adults diagnosed with cancer ≤ 1 year before or any time after HIV diagnosis from January 1, 2000-June 30, 2015 were retrospectively collected. Cancer cases were classified as AIDS-defining cancers (ADC) and non-AIDS-defining cancers (NADC). The association of mortality with cancer- and HIV-related factors was assessed using Kaplan-Meier curves and Cox proportional hazards models stratified by clinic site and cancer type. Among 15,869 patients, 783 had an eligible cancer diagnosis; 82% were male and median age at cancer diagnosis was 39 years (interquartile range [IQR]: 32-47). Patients were from Brazil (36.5%), Argentina (19.9%), Chile (19.7%), Mexico (19.3%), and Honduras (4.6%). A total of 564 ADC and 219 NADC were diagnosed. Patients with NADC had similar survival probabilities as those with ADC at one year (81% vs. 79%) but lower survival at five years (60% vs. 69%). In the adjusted analysis, risk of mortality increased with detectable viral load (adjusted hazard ratio [aHR] = 1.63, p  = 0.02), age (aHR = 1.02 per year, p  = 0.002) and time between HIV and cancer diagnoses (aHR = 1.03 per year, p  = 0.01). ADC remain the most frequent cancers in the region. Overall mortality was related to detectable viral load and age. Longer-term survival was lower after diagnosis of NADC than for ADC, which may be due to factors unrelated to HIV.

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.

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.

Hyperglycaemia, Insulin Therapy and Critical Penumbral Regions for Prognosis in Acute Stroke: Further Insights from the INSULINFARCT Trial

PubMed Central

Rosso, Charlotte; Pires, Christine; Corvol, Jean-Christophe; Baronnet, Flore; Crozier, Sophie; Leger, Anne; Deltour, Sandrine; Valabregue, Romain; Amor-Sahli, Mélika; Lehéricy, Stéphane; Dormont, Didier; Samson, Yves

2015-01-01

Background Recently, the concept of ‘clinically relevant penumbra’ was defined as an area saved by arterial recanalization and correlated with stroke outcome. This clinically relevant penumbra was located in the subcortical structures, especially the periventricular white matter. Our aims were to confirm this hypothesis, to investigate the impact of admission hyperglycemia and of insulin treatment on the severity of ischemic damages in this area and to study the respective contributions of infarct volume and ischemic damage severity of the clinically relevant penumbra on 3-month outcome. Methods We included 99 patients from the INSULINFARCT trial. Voxel-Based Analysis was carried on the Apparent Diffusion Coefficient (ADC) maps obtained at day one to localize the regions, which were more damaged in patients i) with poor clinical outcomes at three months and ii) without arterial recanalization. We determined the intersection of the detected areas, which represents the clinically relevant penumbra and investigated whether hyperglycemic status and insulin regimen affected the severity of ischemic damages in this area. We performed logistic regression to examine the contribution of infarct volume or early ADC decrease in this strategic area on 3-month outcome. Findings Lower ADC values were found in the corona radiata in patients with poor prognosis (p< 0.0001) and in those without arterial recanalization (p< 0.0001). The tracking analysis showed that lesions in this area interrupted many important pathways. ADC values in this area were lower in hyperglycemic than in normoglycemic patients (average decrease of 41.6 ± 20.8 x10−6mm2/s) and unaffected by the insulin regimen (p: 0.10). ADC values in the clinically relevant penumbra, but not infarct volumes, were significant predictors of 3-month outcome. Conclusion These results confirm that the deep hemispheric white matter is part of the clinically relevant penumbra and show that hyperglycaemia exacerbates the apparition of irreversible ischemic damage within 24 hours in this area. However, early intensive insulin therapy fails to protect this area from infarction. Trial Registration ClinicalTrials.gov NCT00472381 PMID:25793765

Peripheral zone lesions of intermediary risk in multiparametric prostate MRI: Frequency and validation of the PI-RADSv2 risk stratification algorithm based on focal contrast enhancement.

PubMed

Benndorf, Matthias; Waibel, Lorenz; Krönig, Malte; Jilg, Cordula Annette; Langer, Mathias; Krauss, Tobias

2018-02-01

To validate the risk stratification algorithm of the Prostate Imaging Reporting and Data System (PI-RADSv2) for intermediary risk lesions (PI-RADSv2 category 3) in the peripheral zone based on focal contrast enhancement and to compare cancer rates in category 3, upgraded category 4 and category 4 based on markedly low ADC value. We retrospectively analyze 172 consecutive patients undergoing prostate MRI with 315 histopathologically verified lesions. We select all lesions either assigned category 3 or category 4 in the peripheral zone for further analysis. We compare cancer rates with the two-sided chi-squared test. To determine inter-observer agreement about contrast enhancement two blinded radiologists evaluate the subset of category 3 lesions based on the diffusion weighted sequence. The frequency of peripheral PI-RADS 3, upgraded PI-RADS 4 and PI-RADS 4 lesions based on markedly low ADC value is 10.8%, 10.8% and 20.3%, respectively. Cancer rates (significant cancer only) in these subgroups are 8.8% (3/34), 23.5% (8/34) and 40.6% (26/64), P < 0.01. Inter-observer agreement is moderate for evaluation of contrast enhancement with kappa values between 0.46 and 0.5. We demonstrate a trend of increasing cancer rate from PI-RADSv2 category 3 to upgraded category 4 to category 4 based on markedly low ADC value. Peripheral lesions of intermediary risk in the diffusion weighted sequence account for 21.6% of all prostate lesions encountered. Since it is likely that patient management recommendations will be linked to assessment categories in future versions of PI-RADS, cancer rates in upgraded category 4 and category 4 based on markedly low ADC values should be in a similar range. We conclude that in future studies of PI-RADSv2 upgraded category 4 and category 4 based on markedly low ADC value should be reported separately to generate a database for meta-analysis of cancer rates. Copyright © 2017 Elsevier B.V. All rights reserved.

Immunohistochemical and Image Analysis-Based Study Shows That Several Immune Checkpoints are Co-expressed in Non-Small Cell Lung Carcinoma Tumors.

PubMed

Parra, Edwin Roger; Villalobos, Pamela; Zhang, Jiexin; Behrens, Carmen; Mino, Barbara; Swisher, Stephen; Sepesi, Boris; Weissferdt, Annika; Kalhor, Neda; Heymach, John Victor; Moran, Cesar; Zhang, Jianjun; Lee, Jack; Rodriguez-Canales, Jaime; Gibbons, Don; Wistuba, Ignacio I

2018-06-01

The understanding of immune checkpoint molecules' co-expression in non-small cell lung carcinoma (NCLC) is important to potentially design combinatorial immunotherapy approaches. We studied 225 formalin-fixed, paraffin-embedded tumor tissues from stage I-III NCLCs - 142 adenocarcinomas (ADCs) and 83 squamous cell carcinomas (SCCs) - placed in tissue microarrays. Nine immune checkpoint markers were evaluated; four (programmed death ligand 1 [PD-L1], B7-H3, B7-H4, and indoleamine 2,3-dioxygenase 1 [IDO-1]) expressed predominantly in malignant cells (MCs) and five (inducible T cell costimulator, V-set immunoregulatory receptor, T-cell immunoglobulin mucin family member 3, lymphocyte activating 3, and OX40) expressed mostly in stromal tumor-associated inflammatory cells (TAICs). All markers were examined using a quantitative image analysis and correlated with clinicopathologic features, TAICs, and molecular characteristics. Using above the median value as positive expression in MCs and high density of TAICs expressing those markers, we identified higher expression of immune checkpoints in SCC than ADC. Common simultaneous expression by MCs was PD-L1 + B7-H3 + IDO-1 in ADC and PD-L1 + B7-H3, or B7-H3 + B7-H4, in SCC. TAICs expressing checkpoint were significantly higher in current smokers than in never smokers. Almost all the immune checkpoint markers showed positive correlation with TAICs expressing inflammatory cell markers. KRAS-mutant ADC specimens showed higher expression of PD-L1 in MCs and of B7-H3, T-cell immunoglobulin mucin family member 3, and IDO-1 in TAICs than wild type. Kaplan-Meier survival curves showed worse prognosis in ADC patients with higher B7-H4 expression by MCs. We found frequent immunohistochemical co-expression of immune checkpoints in surgically resected NCLC tumors and correlated with tumor histology, smoking history, tumor size, and the density of inflammatory cells and tumor mutational status. Copyright © 2018 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

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.

Value of diffusion-weighted MR imaging in the diagnosis of lymph node metastases in patients with cholangiocarcinoma.

PubMed

Holzapfel, Konstantin; Gaa, Jochen; Schubert, Elaine C; Eiber, Matthias; Kleeff, Joerg; Rummeny, Ernst J; Loos, Martin

2016-10-01

To evaluate diffusion-weighted MR imaging (DWI) in the diagnosis of lymph node metastases in patients with cholangiocarcinoma. In 24 patients with cholangiocarcinoma, MR imaging of the upper abdomen was performed prior to surgery at 1.5 T using a respiratory-triggered single-shot echo-planar imaging (SSEPI) sequence (b values: 50, 300, and 600 s/mm(2)). ADC (apparent diffusion coefficient) values and diameters of regional lymph nodes (LN) were determined. Subsequently, in all patients, surgical exploration and/or resection of the primary tumor and regional LN dissection were performed. Imaging results were correlated with results of histopathologic analysis. ADC values and diameters of benign and malignant LN were compared using the Mann-Whitney U test. In addition, a ROC (receiver operating characteristic curve) analysis was performed. The mean ADC value (×10(-3) mm(2)/s) of metastatic LN (1.21 ± 0.15) was significantly lower than that of benign LN (1.62 ± 0.33, p < 0.001) while there was no significant difference in the mean diameter of malignant (16.8 ± 5.4 mm) and benign LN (14.1 ± 4.0 mm; p = 0.09). Using an ADC value of 1.25 × 10(-3) mm(2)/s as threshold, 91.4% of LN were correctly classified as benign or malignant with a sensitivity/specificity of 83.3%/92.8% and a positive/negative predictive value of 66.7%/96.7%. The area under the ROC curve was 0.93. DWI using a respiratory-triggered SSEPI sequence, according to our preliminary experience, is a promising imaging modality in the differentiation of benign and malignant LN in patients with cholangiocarcinoma.

Diffusion MRI with Semi-Automated Segmentation Can Serve as a Restricted Predictive Biomarker of the Therapeutic Response of Liver Metastasis

PubMed Central

Stephen, Renu M.; Jha, Abhinav K.; Roe, Denise J.; Trouard, Theodore P.; Galons, Jean-Philippe; Kupinski, Matthew A.; Frey, Georgette; Cui, Haiyan; Squire, Scott; Pagel, Mark D.; Rodriguez, Jeffrey J.; Gillies, Robert J.; Stopeck, Alison T.

2015-01-01

Purpose To assess the value of semi-automated segmentation applied to diffusion MRI for predicting the therapeutic response of liver metastasis. Methods Conventional diffusion weighted magnetic resonance imaging (MRI) was performed using b-values of 0, 150, 300 and 450 s/mm2 at baseline and days 4, 11 and 39 following initiation of a new chemotherapy regimen in a pilot study with 18 women with 37 liver metastases from primary breast cancer. A semi-automated segmentation approach was used to identify liver metastases. Linear regression analysis was used to assess the relationship between baseline values of the apparent diffusion coefficient (ADC) and change in tumor size by day 39. Results A semi-automated segmentation scheme was critical for obtaining the most reliable ADC measurements. A statistically significant relationship between baseline ADC values and change in tumor size at day 39 was observed for minimally treated patients with metastatic liver lesions measuring 2–5 cm in size (p = 0.002), but not for heavily treated patients with the same tumor size range (p = 0.29), or for tumors of smaller or larger sizes. ROC analysis identified a baseline threshold ADC value of 1.33 μm2/ms as 75% sensitive and 83% specific for identifying non-responding metastases in minimally treated patients with 2–5 cm liver lesions. Conclusion Quantitative imaging can substantially benefit from a semi-automated segmentation scheme. Quantitative diffusion MRI results can be predictive of therapeutic outcome in selected patients with liver metastases, but not for all liver metastases, and therefore should be considered to be a restricted biomarker. PMID:26284600

Diffusion MRI with Semi-Automated Segmentation Can Serve as a Restricted Predictive Biomarker of the Therapeutic Response of Liver Metastasis.

PubMed

Stephen, Renu M; Jha, Abhinav K; Roe, Denise J; Trouard, Theodore P; Galons, Jean-Philippe; Kupinski, Matthew A; Frey, Georgette; Cui, Haiyan; Squire, Scott; Pagel, Mark D; Rodriguez, Jeffrey J; Gillies, Robert J; Stopeck, Alison T

2015-12-01

To assess the value of semi-automated segmentation applied to diffusion MRI for predicting the therapeutic response of liver metastasis. Conventional diffusion weighted magnetic resonance imaging (MRI) was performed using b-values of 0, 150, 300 and 450s/mm(2) at baseline and days 4, 11 and 39 following initiation of a new chemotherapy regimen in a pilot study with 18 women with 37 liver metastases from primary breast cancer. A semi-automated segmentation approach was used to identify liver metastases. Linear regression analysis was used to assess the relationship between baseline values of the apparent diffusion coefficient (ADC) and change in tumor size by day 39. A semi-automated segmentation scheme was critical for obtaining the most reliable ADC measurements. A statistically significant relationship between baseline ADC values and change in tumor size at day 39 was observed for minimally treated patients with metastatic liver lesions measuring 2-5cm in size (p=0.002), but not for heavily treated patients with the same tumor size range (p=0.29), or for tumors of smaller or larger sizes. ROC analysis identified a baseline threshold ADC value of 1.33μm(2)/ms as 75% sensitive and 83% specific for identifying non-responding metastases in minimally treated patients with 2-5cm liver lesions. Quantitative imaging can substantially benefit from a semi-automated segmentation scheme. Quantitative diffusion MRI results can be predictive of therapeutic outcome in selected patients with liver metastases, but not for all liver metastases, and therefore should be considered to be a restricted biomarker. Copyright © 2015 Elsevier Inc. All rights reserved.

Predictors of Sustained Response to Rivastigmine in Patients With Alzheimer's Disease: A Retrospective Analysis

PubMed Central

Grossberg, George T.; Somogyi, Monique; Meng, Xiangyi

2011-01-01

Objective: The cholinesterase inhibitor rivastigmine is approved for the treatment of mild to moderate Alzheimer's disease. However, it is not possible to predict which individuals will benefit from treatment. This retrospective analysis of an international, 24-week, randomized, double-blind trial aimed to identify the percentage of persons with Alzheimer's disease who have a sustained response with rivastigmine patch, rivastigmine capsules, or placebo; to determine the magnitude of the sustained treatment response; and to investigate baseline patient characteristics predictive of the observed sustained response. Method: Patients who improved on the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog) and Alzheimer's Disease Cooperative Study-Activities of Daily Living scale (ADCS-ADL) at week 16 and maintained at least the week 16 improvement at week 24 were identified as sustained responders. Treatment differences and baseline predictive factors were assessed in patients demonstrating a 1-, 2-, 3-, 4-, or 5-point sustained improvement. The first patient was screened in November 2003 and the last patient completed the study in January 2006. Results: More persons with Alzheimer's disease had sustained improvements on the ADAS-cog and ADCS-ADL with rivastigmine versus placebo. Sustained improvements of 4 or 5 points on the ADAS-cog or ADCS-ADL were demonstrated in the 9.5-mg/24-h rivastigmine patch (24% and 36% of patients, respectively) and 12-mg/d capsule groups (28% on both outcome measures). Factors predictive of a sustained response to treatment included baseline Mini-Mental State Examination, ADAS-cog, and ADCS-ADL scores and treatment, country of treatment, and time since first symptom was diagnosed by a physician. Conclusions: Understanding factors predictive of sustained cholinesterase inhibitor treatment response should help to optimize Alzheimer's disease management and encourage compliance by allowing more realistic expectations of treatment effects. PMID:21977379

Predictors of sustained response to rivastigmine in patients with Alzheimer's disease: a retrospective analysis.

PubMed

Sadowsky, Carl H; Grossberg, George T; Somogyi, Monique; Meng, Xiangyi

2011-01-01

The cholinesterase inhibitor rivastigmine is approved for the treatment of mild to moderate Alzheimer's disease. However, it is not possible to predict which individuals will benefit from treatment. This retrospective analysis of an international, 24-week, randomized, double-blind trial aimed to identify the percentage of persons with Alzheimer's disease who have a sustained response with rivastigmine patch, rivastigmine capsules, or placebo; to determine the magnitude of the sustained treatment response; and to investigate baseline patient characteristics predictive of the observed sustained response. Patients who improved on the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog) and Alzheimer's Disease Cooperative Study-Activities of Daily Living scale (ADCS-ADL) at week 16 and maintained at least the week 16 improvement at week 24 were identified as sustained responders. Treatment differences and baseline predictive factors were assessed in patients demonstrating a 1-, 2-, 3-, 4-, or 5-point sustained improvement. The first patient was screened in November 2003 and the last patient completed the study in January 2006. More persons with Alzheimer's disease had sustained improvements on the ADAS-cog and ADCS-ADL with rivastigmine versus placebo. Sustained improvements of 4 or 5 points on the ADAS-cog or ADCS-ADL were demonstrated in the 9.5-mg/24-h rivastigmine patch (24% and 36% of patients, respectively) and 12-mg/d capsule groups (28% on both outcome measures). Factors predictive of a sustained response to treatment included baseline Mini-Mental State Examination, ADAS-cog, and ADCS-ADL scores and treatment, country of treatment, and time since first symptom was diagnosed by a physician. Understanding factors predictive of sustained cholinesterase inhibitor treatment response should help to optimize Alzheimer's disease management and encourage compliance by allowing more realistic expectations of treatment effects.