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.

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

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.

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

PubMed

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

2017-05-01

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

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

PubMed

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

2014-08-01

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

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.

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.

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%.

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

PubMed

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

2015-08-01

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

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.

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.

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.

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.

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.

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.

Progress in Low-Power Digital Microwave Radiometer Technologies

NASA Technical Reports Server (NTRS)

Piepmeier, Jeffrey R.; Kim, Edward J.

2004-01-01

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

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.

[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).

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

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.

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.

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

PubMed

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

2017-10-02

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

Correlation between 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.

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.

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.

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.

Distributed Continuous Event-Based Data Acquisition Using the IEEE 1588 Synchronization and FlexRIO FPGA

NASA Astrophysics Data System (ADS)

Taliercio, C.; Luchetta, A.; Manduchi, G.; Rigoni, A.

2017-07-01

High-speed event driven acquisition is normally performed by analog-to-digital converter (ADC) boards with a given number of pretrigger sample and posttrigger sample that are recorded upon the occurrence of a hardware trigger. A direct physical connection is, therefore, required between the source of event (trigger) and the ADC, because any other software-based communication method would introduce a delay in triggering that would turn out to be not acceptable in many cases. This paper proposes a solution for the relaxation of the event communication time that can be, in this case, carried out by software messaging (e.g., via an LAN), provided that the system components are synchronized in time using the IEEE 1588 synchronization mechanism. The information about the exact event occurrence time is contained in the software packet that is sent to communicate the event and is used by the ADC FPGA to identify the exact sample in the ADC sample queue. The length of the ADC sample queue will depend on the maximum delay in software event message communication time. A prototype implementation using a National FlexRIO FPGA board connected with an ADC device is presented as the proof of concept.

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

PubMed

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

2015-09-01

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

A 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.

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.

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.

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.

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

PubMed

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

2015-01-01

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

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.

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

PubMed

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

2015-08-15

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

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

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%.

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

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

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.

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.

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.

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.

[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.

How do Residents of Recovery Houses Experience Confrontation between Entry and 12-Month Follow-Up?

PubMed Central

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

2010-01-01

The role of confrontation in recovery has been vigorously debated. Proponents suggest that confrontation can help break down denial and increase motivation. Critics point to counseling studies showing confrontation harms the therapeutic alliance and increases resistance. Frequently missing in these debates is an operational definition of confrontation that can be reliably measured. The Alcohol and Drug Confrontation Scale (ADCS) is a new 72-item measure that defines confrontation as “warnings about potential harm” that might result from substance use. Previous psychometric work using a sample of residents of recovery homes at intake (N=323) indicated the ADCS had acceptable reliability and validity. Confrontation from different sources (e.g., family, friends and professionals) was generally experienced as supportive and helpful. The goals of the current study were twofold: 1) to see if the psychometric properties of the ADCS were maintained at 6 and 12 month follow up, and 2) to see if experiences and perceptions of confrontation changed over time. Despite minor variations in the factor structure between baseline and follow up, the ADCS generally maintained good reliability and validity. At follow up, the amount of confrontation participants received declined, but it continued to be generally experienced as supportive and helpful. PMID:20464806

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

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

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.

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.

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.

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

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.

Evaluation of dual-source parallel RF excitation for diffusion-weighted whole-body MR imaging with background body signal suppression at 3.0 T.

PubMed

Mürtz, Petra; Kaschner, Marius; Träber, Frank; Kukuk, Guido M; Büdenbender, Sarah M; Skowasch, Dirk; Gieseke, Jürgen; Schild, Hans H; Willinek, Winfried A

2012-11-01

To evaluate the use of dual-source parallel RF excitation (TX) for diffusion-weighted whole-body MRI with background body signal suppression (DWIBS) at 3.0 T. Forty consecutive patients were examined on a clinical 3.0-T MRI system using a diffusion-weighted (DW) spin-echo echo-planar imaging sequence with a combination of short TI inversion recovery and slice-selective gradient reversal fat suppression. DWIBS of the neck (n=5), thorax (n=8), abdomen (n=6) and pelvis (n=21) was performed both with TX (2:56 min) and with standard single-source RF excitation (4:37 min). The quality of DW images and reconstructed inverted maximum intensity projections was visually judged by two readers (blinded to acquisition technique). Signal homogeneity and fat suppression were scored as "improved", "equal", "worse" or "ambiguous". Moreover, the apparent diffusion coefficient (ADC) values were measured in muscles, urinary bladder, lymph nodes and lesions. By the use of TX, signal homogeneity was "improved" in 25/40 and "equal" in 15/40 cases. Fat suppression was "improved" in 17/40 and "equal" in 23/40 cases. These improvements were statistically significant (p<0.001, Wilcoxon signed-rank test). In five patients, fluid-related dielectric shading was present, which improved remarkably. The ADC values did not significantly differ for the two RF excitation methods (p=0.630 over all data, pairwise Student's t-test). Dual-source parallel RF excitation improved image quality of DWIBS at 3.0 T with respect to signal homogeneity and fat suppression, reduced scan time by approximately one-third, and did not influence the measured ADC values. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

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.

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

PubMed

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

2014-05-10

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

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

PubMed Central

2014-01-01

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

The effects of inulin supplementation of diets with or without hydrolysed protein sources on digestibility, faecal characteristics, haematology and immunoglobulins in dogs.

PubMed

Verlinden, A; Hesta, M; Hermans, J M; Janssens, G P J

2006-11-01

Dogs with food allergy are often treated by giving a diet with hydrolysed protein sources. Prebiotics might also be successful in prevention and treatment of allergic disease through their effect on the colonic microflora, analogous to studies on probiotics in allergic children. The present study was set up to investigate the effect of supplementing inulin (IN) to commercial hypoallergenic dog diets on apparent nutrient digestibility, faecal characteristics, haematology and Ig in dogs. Supplementation of 3 % IN did not affect faecal pH, food and water intake and urine production. Compared with the intact protein diet with a limited number of ingredients (L), the diet with a hydrolysed protein source (H) resulted in an increased water intake (P<0.001), which could be due to the osmotic effect of free amino acids. Faeces production was increased by IN due to increased faecal moisture content. Increased faeces production on the H diet was mainly due to a higher DM excretion. Subsequently, the apparent digestibility coefficient (ADC) of DM was lower in the H diet group. A similar result was noted for ADC of diethyl ether extract and crude ash. The ADC of crude protein was higher in the H diet group, whereas IN decreased the ADC of crude protein. Differences in the ADC of crude protein among the different diets disappeared after correction for a higher faecal biomass, except for the dogs fed the L+IN diet. Total faecal IgA concentrations were lower in the H group (P<0.05) because of lower antigenic stimulation of hydrolysed protein, which implies that hydrolysed protein is really hypoallergenic. The present study indicates that the use of hydrolysed protein diets for canine food allergy treatment can affect digestibility and that combination with IN affected apparent protein digestibility but not IgA response.

The performance of PI-RADSv2 and quantitative apparent diffusion coefficient for predicting confirmatory prostate biopsy findings in patients considered for active surveillance of prostate cancer.

PubMed

Nougaret, Stephanie; Robertson, Nicola; Golia Pernicka, Jennifer; Molinari, Nicolas; Hötker, Andreas M; Ehdaie, Behfar; Sala, Evis; Hricak, Hedvig; Vargas, Hebert Alberto

2017-07-01

To assess the performance of the updated Prostate Imaging Reporting and Data System (PI-RADSv2) and the apparent diffusion coefficient (ADC) for predicting confirmatory biopsy results in patients considered for active surveillance of prostate cancer (PCA). IRB-approved, retrospective study of 371 consecutive men with clinically low-risk PCA (initial biopsy Gleason score ≤6, prostate-specific antigen <10 ng/ml, clinical stage ≤T2a) who underwent 3T-prostate MRI before confirmatory biopsy. Two independent radiologists recorded the PI-RADSv2 scores and measured the corresponding ADC values in each patient. A composite score was generated to assess the performance of combining PI-RADSv2 + ADC. PCA was upgraded on confirmatory biopsy in 107/371 (29%) patients. Inter-reader agreement was substantial (PI-RADSv2: k = 0.73; 95% CI [0.66-0.80]; ADC: r = 0.74; 95% CI [0.69-0.79]). Accuracies, sensitivities, specificities, positive predicted value and negative predicted value of PI-RADSv2 were 85, 89, 83, 68, 95 and 78, 82, 76, 58, 91% for ADC. PI-RADSv2 accuracy was significantly higher than that of ADC for predicting biopsy upgrade (p = 0.014). The combined PI-RADSv2 + ADC composite score did not perform better than PI-RADSv2 alone. Obviating biopsy in patients with PI-RADSv2 score ≤3 would have missed Gleason Score upgrade in 12/232 (5%) of patients. PI-RADSv2 was superior to ADC measurements for predicting PCA upgrading on confirmatory biopsy.

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

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.

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.

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.

A fresh look at the photoelectron spectrum of bromobenzene: A third-order non-Dyson electron propagator study.

PubMed

Schneider, M; Soshnikov, D Yu; Holland, D M P; Powis, I; Antonsson, E; Patanen, M; Nicolas, C; Miron, C; Wormit, M; Dreuw, A; Trofimov, A B

2015-10-14

The valence-shell ionization spectrum of bromobenzene, as a representative halogen substituted aromatic, was studied using the non-Dyson third-order algebraic-diagrammatic construction [nD-ADC(3)] approximation for the electron propagator. This method, also referred to as IP-ADC(3), was implemented as a part of the Q-Chem program and enables large-scale calculations of the ionization spectra, where the computational effort scales as n(5) with respect to the number of molecular orbitals n. The IP-ADC(3) scheme is ideally suited for investigating low-lying ionization transitions, so fresh insight could be gained into the cationic state manifold of bromobenzene. In particular, the present IP-ADC(3) calculations with the cc-pVTZ basis reveal a whole class of low-lying low-intensity two-hole-one-particle (2h-1p) doublet and quartet states, which are relevant to various photoionization processes. The good qualitative agreement between the theoretical spectral profile for the valence-shell ionization transitions generated with the smaller cc-pVDZ basis set and the experimental photoelectron spectrum measured at a photon energy of 80 eV on the PLÉIADES beamline at the Soleil synchrotron radiation source allowed all the main features to be assigned. Some theoretical aspects of the ionization energy calculations concerning the use of various approximation schemes and basis sets are discussed.

A fresh look at the photoelectron spectrum of bromobenzene: A third-order non-Dyson electron propagator study

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

Schneider, M.; Wormit, M.; Dreuw, A.

2015-10-14

The valence-shell ionization spectrum of bromobenzene, as a representative halogen substituted aromatic, was studied using the non-Dyson third-order algebraic-diagrammatic construction [nD-ADC(3)] approximation for the electron propagator. This method, also referred to as IP-ADC(3), was implemented as a part of the Q-Chem program and enables large-scale calculations of the ionization spectra, where the computational effort scales as n{sup 5} with respect to the number of molecular orbitals n. The IP-ADC(3) scheme is ideally suited for investigating low-lying ionization transitions, so fresh insight could be gained into the cationic state manifold of bromobenzene. In particular, the present IP-ADC(3) calculations with the cc-pVTZmore » basis reveal a whole class of low-lying low-intensity two-hole-one-particle (2h-1p) doublet and quartet states, which are relevant to various photoionization processes. The good qualitative agreement between the theoretical spectral profile for the valence-shell ionization transitions generated with the smaller cc-pVDZ basis set and the experimental photoelectron spectrum measured at a photon energy of 80 eV on the PLÉIADES beamline at the Soleil synchrotron radiation source allowed all the main features to be assigned. Some theoretical aspects of the ionization energy calculations concerning the use of various approximation schemes and basis sets are discussed.« less

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.

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.

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

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.

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.

Diffusion-weighted magnetic resonance imaging using different b-value combinations for the evaluation of treatment results after volumetric MR-guided high-intensity focused ultrasound ablation of uterine fibroids.

PubMed

Ikink, Marlijne E; Voogt, Marianne J; van den Bosch, Maurice A A J; Nijenhuis, Robbert J; Keserci, Bilgin; Kim, Young-sun; Vincken, Koen L; Bartels, Lambertus W

2014-09-01

To assess the value of diffusion-weighted magnetic resonance imaging (DWI) and apparent diffusion coefficient (ADC) mapping using different b-value combinations for treatment evaluation after magnetic resonance-guided high-intensity focused ultrasound (MR-HIFU) of uterine fibroids. Fifty-six patients with 67 uterine fibroids were treated with volumetric MR-HIFU. Pre-treatment and post-treatment images were obtained using contrast-enhanced T1-weighted MRI (CE-T1WI) and DWI using b = 0, 200, 400, 600, 800 s/mm(2). ADC maps were generated using subsets of b-values to investigate the effects of tissue ablation on water diffusion and perfusion in fibroids treated with MR-HIFU. Four combinations of b-values were used: (1) all b-values; (2) b = 0, 200 s/mm(2); (3) b = 400, 600, 800 s/mm(2); and (4) b = 0, 800 s/mm(2). Using the lowest b-values (0 and 200 s/mm(2)), the mean ADC value in the ablated tissue reduced significantly (p < 0.001) compared with baseline. Calculating the ADC value with the highest b-values (400, 600, 800 s/mm(2)), the ADC increased significantly (p < 0.001) post-treatment. ADC maps calculated with the lowest b-values resulted in the best visual agreement of non-perfused fibroid tissue detected on CE images. Other b-value combinations and normal myometrium showed no difference in ADC after MR-HIFU treatment. A decrease in contrast agent uptake within the ablated region on CE-T1WI was correlated to a significantly decreased ADC when b = 0 and 200 s/mm(2) were used. DWI could be useful for treatment evaluation after MR-HIFU of uterine fibroids. The ADC in fibroid tissue is influenced by the choice of b- values. Low b-values seem the best choice to emphasise perfusion effects after MR-HIFU.

VHDL implementation of feature-extraction algorithm for the PANDA electromagnetic calorimeter

NASA Astrophysics Data System (ADS)

Guliyev, E.; Kavatsyuk, M.; Lemmens, P. J. J.; Tambave, G.; Löhner, H.; Panda Collaboration

2012-02-01

A simple, efficient, and robust feature-extraction algorithm, developed for the digital front-end electronics of the electromagnetic calorimeter of the PANDA spectrometer at FAIR, Darmstadt, is implemented in VHDL for a commercial 16 bit 100 MHz sampling ADC. The source-code is available as an open-source project and is adaptable for other projects and sampling ADCs. Best performance with different types of signal sources can be achieved through flexible parameter selection. The on-line data-processing in FPGA enables to construct an almost dead-time free data acquisition system which is successfully evaluated as a first step towards building a complete trigger-less readout chain. Prototype setups are studied to determine the dead-time of the implemented algorithm, the rate of false triggering, timing performance, and event correlations.

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.

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

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

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

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.

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

PubMed

Koontz, Nicholas A; Wiggins, Richard H

2017-05-01

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

Utility of Diffusion-Weighted 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.

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.

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

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.

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.

HER2 monoclonal antibodies that do not interfere with receptor heterodimerization-mediated signaling induce effective internalization and represent valuable components for rational antibody-drug conjugate design.

PubMed

de Goeij, Bart E C G; Peipp, Matthias; de Haij, Simone; van den Brink, Edward N; Kellner, Christian; Riedl, Thilo; de Jong, Rob; Vink, Tom; Strumane, Kristin; Bleeker, Wim K; Parren, Paul W H I

2014-01-01

The human epidermal growth factor receptor (HER)2 provides an excellent target for selective delivery of cytotoxic drugs to tumor cells by antibody-drug conjugates (ADC) as has been clinically validated by ado-trastuzumab emtansine (Kadcyla(TM)). While selecting a suitable antibody for an ADC approach often takes specificity and efficient antibody-target complex internalization into account, the characteristics of the optimal antibody candidate remain poorly understood. We studied a large panel of human HER2 antibodies to identify the characteristics that make them most suitable for an ADC approach. As a model toxin, amenable to in vitro high-throughput screening, we employed Pseudomonas exotoxin A (ETA') fused to an anti-kappa light chain domain antibody. Cytotoxicity induced by HER2 antibodies, which were thus non-covalently linked to ETA', was assessed for high and low HER2 expressing tumor cell lines and correlated with internalization and downmodulation of HER2 antibody-target complexes. Our results demonstrate that HER2 antibodies that do not inhibit heterodimerization of HER2 with related ErbB receptors internalize more efficiently and show greater ETA'-mediated cytotoxicity than antibodies that do inhibit such heterodimerization. Moreover, stimulation with ErbB ligand significantly enhanced ADC-mediated tumor kill by antibodies that do not inhibit HER2 heterodimerization. This suggests that the formation of HER2/ErbB-heterodimers enhances ADC internalization and subsequent killing of tumor cells. Our study indicates that selecting HER2 ADCs that allow piggybacking of HER2 onto other ErbB receptors provides an attractive strategy for increasing ADC delivery and tumor cell killing capacity to both high and low HER2 expressing tumor cells.

Diffusion-weighted MR imaging: role in the differential diagnosis of breast lesions.

PubMed

Altay, C; Balci, P; Altay, S; Karasu, S; Saydam, S; Canda, T; Dicle, O

2014-01-01

To evaluate the diagnostic value of magnetic resonance diffusion-weighted imaging (DWI) using apparent diffusion coefficient (ADC) values to the characterization of breast lesions and differentiation of benign and malignant lesions. Thirty-seven women (mean age, 38 years) with 37 enrolled in the study. DWI and ADC maps in the axial plane were obtained using a 1.5 Tesla MRI device. Mean ADC measurements were calculated among cysts, normal fibroglandular tissue, benign lesions and malignant lesions were evaluated. Out of 37 women, 4 had normally breast MRI findings. The diagnosis of remaining 33 patients with 37 breast lesions were as follows; malign lesions (n = 23), benign lesions (n = 10) and simple breast cyst (n = 4). The ADC values were as follows (in units of 10(-3) mm2/s): Normal fibroglandular tissue (range: 1.39-2.06; mean: 1.61 ± 0.23), benign breast lesions (range: 1.09-1.76; mean: 1.47 ± 0.25), cyts (range: 2.27-2.46, mean: 2.37 ± 0.07) and malignant breast lesions (range: 0.78-1.26, mean: 0.96 ± 0.25). The mean ADC obtained from malignant breast lesions was statistically different from that observed in benign solid lesions (p < < 0.01) and normal fibroglandular breast tissue (p < 0.01). Furthermore, the mean ADC values of benign breast lesions was not statistically different from cyst (p ≥ 0.01) and normal fibroglandular breast tissue (p ≥ 0.01). A ADC value of 1.1 x 10(-3) mm'/s as a treshold value provided differantiation for malign and benign lesions, with a sensitivity of 91.3% and a specificity of 85.7% compared with conventional breast MRI values. DWI with quantitative ADC measurements is a reliable tool for differentiation of benign and malignant breast lesions.

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

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.

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

PubMed

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

2015-12-01

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

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.

Self-balanced real-time photonic scheme for ultrafast random number generation

NASA Astrophysics Data System (ADS)

Li, Pu; Guo, Ya; Guo, Yanqiang; Fan, Yuanlong; Guo, Xiaomin; Liu, Xianglian; Shore, K. Alan; Dubrova, Elena; Xu, Bingjie; Wang, Yuncai; Wang, Anbang

2018-06-01

We propose a real-time self-balanced photonic method for extracting ultrafast random numbers from broadband randomness sources. In place of electronic analog-to-digital converters (ADCs), the balanced photo-detection technology is used to directly quantize optically sampled chaotic pulses into a continuous random number stream. Benefitting from ultrafast photo-detection, our method can efficiently eliminate the generation rate bottleneck from electronic ADCs which are required in nearly all the available fast physical random number generators. A proof-of-principle experiment demonstrates that using our approach 10 Gb/s real-time and statistically unbiased random numbers are successfully extracted from a bandwidth-enhanced chaotic source. The generation rate achieved experimentally here is being limited by the bandwidth of the chaotic source. The method described has the potential to attain a real-time rate of 100 Gb/s.

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

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.

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.

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.

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.

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

Not Available

The Anderson Development Company (ADC) site has been placed on the National Priorities List (NPL). From approximately 1968 to 1979 ADC manufactured 4,4'-methylene-bis(2-chloroaniline) (MBOCA), also known under the trademark names of MOCA and Curene 422. In 1978 the National Institute for Occupational Safety and Health recommended that MBOCA be regulated as a human carcinogen. Discharges of waste waters and air emissions from ADC during the production of MBOCA eventually caused contamination in company lagoons, sludges, and effluents; in municipal sewer influent, effluent, and sludges; in surface-water drains and the Raisin River; and in soil, street sweepings, and residences within amore » 1-mile radius of the plant. In 1979 and 1980, detectable levels of MBOCA were found in urine specimens collected from ADC and user-plant employees and members of their families. MBOCA may have been carried out of the manufacturing plant on the shoes and clothing of the employees and deposited in their residence. Detectable concentrations of MBOCA were also found in urine specimens of some children living near the site. Because the documented contamination created a continuing potential for environment and human exposure, comprehensive remedial measures were implemented during 1980 and 1981. The site is of potential public health concern because a risk to human health may exist from possible exposure to a hazardous substance at levels that may result in adverse health effects over time; human exposure to MBOCA has occurred/may be still occurring via contaminated soil and garden sources of food.« less

[Correlations between MRI apparent diffusion coefficient and histological grade and molecular biology of breast invasive ductal carcinoma].

PubMed

Yu, Xuejuan; Liu, Shangang; Chen, Zhaoqiu; Zhang, Pinliang; Zhang, Jianbo; Xu, Liang; Liu, Zengjun; Ren, Ruimei

2014-08-01

To study the correlation between the MRI apparent diffusion coefficient (ADC) value and histological grade and molecular biology of breast invasive ductal carcinoma (IDC). This retrospective study included 125 patients with IDC verified by pathology from February 2010 to February 2013. Conventional MRI and diffusion-weighted imaging (DWI) examination were performed using a 3.0T scanner with diffusion factor of 0 and 800 s/mm(2). The region of interest (ROI) was drawn on the largest lesion and/or its two adjacent slices. The ADC value of the whole tumor was calculated as the mean ADC value. The correlation between mean ADCs and histological grade and biological factors was analyzed. The mean ADC of pathological grade I, II and III IDC was (1.152 ± 0.072)×10(-3) mm(2)/s, (1.102 ± 0.101)×10(-3) mm(2)/s, and (1.035 ± 0.107)×10(-3) mm(2)/s, respectively. There was a statistically significant difference among them (P = 0.003). Statistically a significant difference was observed between grade III and I (P = 0.034), grade III and II (P = 0.006), but not between grade I and II (P = 0.741). A significant correlation was observed between ADC value and pathological grade (r = -0.342, P < 0.001). The median ADC values were significantly higher in the ER-negative than in the ER-positive cases [(1.130 ± 0.115)×10(-3) mm(2)/s vs. (1.060 ± 0.089) ×10(-3) mm(2)/s, P < 0.001)], in PR-negative than in PR-positive cases [(1.121 ± 0.106)×10(-3) mm(2)/s vs. (1.055 ± 0.096) ×10(-3) mm(2)/s, P < 0.001)], and in Ki-67-negative than in Ki-67-positive cases [(1.153 ± 0.090)×10(-3) mm(2)/s vs. (1.063 ± 0.101) ×10(-3) mm(2)/s, P < 0.001]. A statistically significant correlation was observed between ADC value and expressions of ER, PR, and Ki-67 (r = -0.311, r = -0.317, r = -0.414, P < 0.001). ADC value of breast invasive ductal carcinoma is correlated with histological grade, and expression of ER, PR and Ki-67.

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.

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

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

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

2012-03-01

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

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

PubMed

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

2010-08-01

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

Preparation of astaxanthin-loaded DNA/chitosan nanoparticles for improved cellular uptake and antioxidation capability.

PubMed

Wang, Qian; Zhao, Yingyuan; Guan, Lei; Zhang, Yaping; Dang, Qifeng; Dong, Ping; Li, Jing; Liang, Xingguo

2017-07-15

DNA/chitosan co-assemblies were initially used as nanocarriers for efficient astaxanthin encapsulation and delivery. The obtained astaxanthin-loaded DNA/chitosan (ADC) colloidal system was transparent and homogenous, with astaxanthin content up to 65μg/ml. Compared to free astaxanthin, ADC nanoparticles with an astaxanthin concentration as low as 3.35nM still showed a more powerful cytoprotective effect on H 2 O 2 -induced oxidative cell damage, and improved cell viability from 49.9% to 61.9%. The ROS scavenging efficiency of ADC nanoparticles was as high as 54.3%, which was 2-fold higher than that of free astaxanthin. Besides this, ADC nanoparticles were easily engulfed by Caco-2 cells in a short time, indicating that the encapsulated astaxanthin could be absorbed through endocytosis by intestinal epithelial cells. The improved antioxidation capability and facilitated cellular uptake enabled the ADC nanoparticles to be good candidates for efficient delivery and absorption of astaxanthin. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

TRPC4α and TRPC4β Similarly Affect Neonatal Cardiomyocyte Survival during Chronic GPCR Stimulation

PubMed Central

Kirschmer, Nadine; Bandleon, Sandra; von Ehrlich-Treuenstätt, Viktor; Hartmann, Sonja; Schaaf, Alice; Lamprecht, Anna-Karina; Miranda-Laferte, Erick; Langsenlehner, Tanja; Ritter, Oliver; Eder, Petra

2016-01-01

The Transient Receptor Potential Channel Subunit 4 (TRPC4) has been considered as a crucial Ca2+ component in cardiomyocytes promoting structural and functional remodeling in the course of pathological cardiac hypertrophy. TRPC4 assembles as homo or hetero-tetramer in the plasma membrane, allowing a non-selective Na+ and Ca2+ influx. Gαq protein-coupled receptor (GPCR) stimulation is known to increase TRPC4 channel activity and a TRPC4-mediated Ca2+ influx which has been regarded as ideal Ca2+ source for calcineurin and subsequent nuclear factor of activated T-cells (NFAT) activation. Functional properties of TRPC4 are also based on the expression of the TRPC4 splice variants TRPC4α and TRPC4β. Aim of the present study was to analyze cytosolic Ca2+ signals, signaling, hypertrophy and vitality of cardiomyocytes in dependence on the expression level of either TRPC4α or TRPC4β. The analysis of Ca2+ transients in neonatal rat cardiomyocytes (NRCs) showed that TRPC4α and TRPC4β affected Ca2+ cycling in beating cardiomyocytes with both splice variants inducing an elevation of the Ca2+ transient amplitude at baseline and TRPC4β increasing the Ca2+ peak during angiotensin II (Ang II) stimulation. NRCs infected with TRPC4β (Ad-C4β) also responded with a sustained Ca2+ influx when treated with Ang II under non-pacing conditions. Consistent with the Ca2+ data, NRCs infected with TRPC4α (Ad-C4α) showed an elevated calcineurin/NFAT activity and a baseline hypertrophic phenotype but did not further develop hypertrophy during chronic Ang II/phenylephrine stimulation. Down-regulation of endogenous TRPC4α reversed these effects, resulting in less hypertrophy of NRCs at baseline but a markedly increased hypertrophic enlargement after chronic agonist stimulation. Ad-C4β NRCs did not exhibit baseline calcineurin/NFAT activity or hypertrophy but responded with an increased calcineurin/NFAT activity after GPCR stimulation. However, this effect was not translated into an increased propensity towards hypertrophy but rather less hypertrophy during GPCR stimulation. Further analyses revealed that, although hypertrophy was preserved in Ad-C4α NRCs and even attenuated in Ad-C4β NRCs, cardiomyocytes had an increased apoptosis rate and thus were less viable after chronic GPCR stimulation. These findings suggest that TRPC4α and TRPC4β differentially affect Ca2+ signals, calcineurin/NFAT signaling and hypertrophy but similarly impair cardiomyocyte viability during GPCR stimulation. PMID:27992507

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.

ADC Quantification of the Vertebral Bone Marrow Water Component: Removing the Confounding Effect of Residual Fat.

PubMed

Dieckmeyer, Michael; Ruschke, Stefan; Eggers, Holger; Kooijman, Hendrik; Rummeny, Ernst J; Kirschke, Jan S; Baum, Thomas; Karampinos, Dimitrios C

2017-10-01

To remove the confounding effect of unsuppressed fat on the imaging-based apparent diffusion coefficient (ADC) of the vertebral bone marrow water component when using spectrally selective fat suppression and to compare and validate the proposed quantification strategy against diffusion-weighted magnetic resonance spectroscopy (DW-MRS). Twelve subjects underwent diffusion-weighted imaging (DWI) and DW-MRS of the vertebral bone marrow. A theoretical model was developed to take into account and correct the effects of residual fat on ADC, incorporating additional measurements for proton density fat fraction (PDFF) and water T 2 (T 2w ). Uncorrected and corrected DWI-based ADC was compared with DW-MRS-based ADC using the Bland-Altman method. There was a systematic bias equal to 0.118 ± 0.116 × 10 -3 mm 2 /s between DWI and DW-MRS when no correction was performed. Taking into account measured PDFF and constant T 2w reduced the bias to 0.006 ± 0.128 × 10 -3 mm 2 /s. Using the proposed approach with both individually measured PDFF and T 2w reduced both the bias and the limits of agreement between DWI and DW-MRS (0.018 ± 0.065 × 10 -3 mm 2 /s). By taking into account the presence of residual fat in a modified signal model that incorporates additional individual measurements of PDFF and T 2w , good agreement of imaging-based ADC with MRS-based ADC can be achieved in vertebral bone marrow. Magn Reson Med 78:1432-1441, 2017. © 2016 International Society for Magnetic Resonance in Medicine. © 2016 International Society for Magnetic Resonance in Medicine.

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.

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.

Texture features on T2-weighted magnetic resonance imaging: new potential biomarkers for prostate cancer aggressiveness

NASA Astrophysics Data System (ADS)

Vignati, A.; Mazzetti, S.; Giannini, V.; Russo, F.; Bollito, E.; Porpiglia, F.; Stasi, M.; Regge, D.

2015-04-01

To explore contrast (C) and homogeneity (H) gray-level co-occurrence matrix texture features on T2-weighted (T2w) Magnetic Resonance (MR) images and apparent diffusion coefficient (ADC) maps for predicting prostate cancer (PCa) aggressiveness, and to compare them with traditional ADC metrics for differentiating low- from intermediate/high-grade PCas. The local Ethics Committee approved this prospective study of 93 patients (median age, 65 years), who underwent 1.5 T multiparametric endorectal MR imaging before prostatectomy. Clinically significant (volume ≥0.5 ml) peripheral tumours were outlined on histological sections, contoured on T2w and ADC images, and their pathological Gleason Score (pGS) was recorded. C, H, and traditional ADC metrics (mean, median, 10th and 25th percentile) were calculated on the largest lesion slice, and correlated with the pGS through the Spearman correlation coefficient. The area under the receiver operating characteristic curve (AUC) assessed how parameters differentiate pGS = 6 from pGS ≥ 7. The dataset included 49 clinically significant PCas with a balanced distribution of pGS. The Spearman ρ and AUC values on ADC were: -0.489, 0.823 (mean) -0.522, 0.821 (median) -0.569, 0.854 (10th percentile) -0.556, 0.854 (25th percentile) -0.386, 0.871 (C); 0.533, 0.923 (H); while on T2w they were: -0.654, 0.945 (C); 0.645, 0.962 (H). AUC of H on ADC and T2w, and C on T2w were significantly higher than that of the mean ADC (p = 0.05). H and C calculated on T2w images outperform ADC parameters in correlating with pGS and differentiating low- from intermediate/high-risk PCas, supporting the role of T2w MR imaging in assessing PCa biological aggressiveness.

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

PubMed

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

2017-05-01

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

Use of quantitative diffusion-weighted magnetic resonance imaging to predict human papilloma virus status in patients with oropharyngeal squamous cell carcinoma.

PubMed

Nakahira, Mitsuhiko; Saito, Naoko; Yamaguchi, Hiroshi; Kuba, Kiyomi; Sugasawa, Masashi

2014-05-01

Although identification of human papilloma virus (HPV) status in oropharyngeal squamous cell carcinoma (OPSCC) is essential in predicting treatment response, no imaging modality can currently determine whether a tumor is HPV-related. In this retrospective study, 26 patients with OPSCC confined to the lateral wall or the base of tongue underwent neck magnetic resonance imaging, using T1-, T2- and diffusion-weighted imaging (DWI). Apparent diffusion coefficients (ADCs) in a region of interest covering the largest available primary tumor area of OPSCC on a single slice of the ADC map were calculated using two b values (0 and 1,000 s/mm(2)). Mean and minimum ADCs were compared with HPV status, using p16 immunohistochemistry as a surrogate marker for HPV infection. Mean and minimum ADCs for HPV(+) OPSCC were significantly lower than those for HPV(-) OPSCC. A cut-off value of mean ADC for HPV(+) OPSCC of 1.027 × 10(-3) mm(2)/s yielded sensitivity and specificity of 83.33 and 78.57%, respectively. In conclusion, the present study indicates that ADC could be used to predict HPV status in patients with OPSCC.

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.

Evaluation of the apparent diffusion coefficient in patients with recurrent glioblastoma under treatment with bevacizumab with radiographic pseudoresponse.

PubMed

A Auer, Timo; Breit, Hanns-Christian; Marini, Federico; Renovanz, Mirjam; A Brockmann, Marc; Tanyildizi, Yasemin

2018-05-04

Response Assessment in Neuro-Oncology Criteria (RANO), are used to asses response to first-line treatment of glioblastoma (GBM). Differentiation between response and pseudoresponse under treatment with Bevacizumab (BVZ) remains challenging. This study evaluates ADC changes in patients with radiographic pseudoresponse under treatment with (BVZ). Patients (n=40) with recurrent GBM under-treatment with BVZ underwent MRI before, two and four months after treatment with BVZ. In patients with radiological pseudoresponse (n=11), ADC analyses were performed. Areas with decreasing T1 contrast enhancement (CE) and FLAIR signal decrease were manually selected and compared to size and position matched healthy contralateral brain parenchyma. Histogram based ADC (10 -6 ×mm 2 /s) of these patients decreased significantly (P<0.005) from baseline MRI (T1-CE, FLAIR: 1124.9±160.3, 1098.4±226.2, respectively) to 2months (781.3±110.7, 783.3±103.3) and remained stable during 4months (777.0±138.5, 784.4±155.4, all mean±1 SD), despite progressive disease. Mean ADC values of the healthy contralateral brain tissue remained stable (P>0.05) (ADC values: baseline: 786.2±110.7, 2months: 781.1±76.2, 4months: 804.1±86.2). Treatment of GBM with BVZ leads to a decrease of ADC values in areas of pre-treatment T1-CE/FLAIR signal hyperintensity to levels of comparable with normal brain tissue. ADC values remained stable, even when progressive tumor growth was reported. Copyright © 2018. Published by Elsevier Masson SAS.

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.

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)

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.

Apparent diffusion coefficient (ADC) does not correlate with different serological parameters in myositis and myopathy.

PubMed

Meyer, Hans-Jonas; Ziemann, Oliver; Kornhuber, Malte; Emmer, Alexander; Quäschling, Ulf; Schob, Stefan; Surov, Alexey

2018-06-01

Background Magnetic resonance imaging (MRI) is widely used in several muscle disorders. Diffusion-weighted imaging (DWI) is an imaging modality, which can reflect microstructural tissue composition. The apparent diffusion coefficient (ADC) is used to quantify the random motion of water molecules in tissue. Purpose To investigate ADC values in patients with myositis and non-inflammatory myopathy and to analyze possible associations between ADC and laboratory parameters in these patients. Material and Methods Overall, 17 patients with several myositis entities, eight patients with non-inflammatory myopathies, and nine patients without muscle disorder as a control group were included in the study (mean age = 55.3 ± 14.3 years). The diagnosis was confirmed by histopathology in every case. DWI was obtained in a 1.5-T scanner using two b-values: 0 and 1000 s/mm 2 . In all patients, the blood sample was acquired within three days to the MRI. The following serological parameters were estimated: C-reactive protein, lactate dehydrogenase, alanine aminotransferase, aspartate aminotransferase, creatine kinase, and myoglobine. Results The estimated mean ADC value for the myositis group was 1.89 ± 0.37 × 10 -3  mm 2 /s and for the non-inflammatory myopathy group was 1.79 ± 0.33 × 10 -3  mm 2 /s, respectively. The mean ADC values (1.15 ± 0.37 × 10 -3  mm 2 /s) were significantly higher to unaffected muscles (vs. myositis P = 0.0002 and vs. myopathy P = 0.0021). There were no significant correlations between serological parameters and ADC values. Conclusion Affected muscles showed statistically significantly higher ADC values than normal muscles. No linear correlations between ADC and serological parameters were identified.

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.

Novel antibody drug conjugates containing exatecan derivative-based cytotoxic payloads.

PubMed

Nakada, Takashi; Masuda, Takeshi; Naito, Hiroyuki; Yoshida, Masao; Ashida, Shinji; Morita, Koji; Miyazaki, Hideki; Kasuya, Yuji; Ogitani, Yusuke; Yamaguchi, Junko; Abe, Yuki; Honda, Takeshi

2016-03-15

Trastuzumab conjugates consisting of exatecan derivatives were prepared and their biological activities and physicochemical properties were evaluated. The ADCs showed strong efficacy and a low aggregation rate. The exatecan derivatives were covalently connected via a peptidyl spacer (Gly-Gly-Phe-Gly), which is assumed to be stable in circulation, and were cleaved by lysosomal enzymes following ADC internalization into tumor tissue. These anti-HER2 ADCs exhibited a high potency, specifically against HER2-positive cancer cell lines in vitro. The ADCs, bearing exatecan derivatives which have more than two methylene chains, exhibited superior cytotoxicity. It was speculated that steric hindrance of the cleavable amide moiety could be involved in the drug release. The adequate alkyl lengths of exatecan derivatives (13, 14, 15) were from two to four in terms of aggregation rate. The ADC having a hydrophilic moiety showed good efficacy in a HER2-positive and Trastuzumab-resistant breast carcinoma cell model in mice. Copyright © 2016 Elsevier Ltd. All rights reserved.

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.

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

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.

Reduced-cost second-order algebraic-diagrammatic construction method for excitation energies and transition moments

NASA Astrophysics Data System (ADS)

Mester, Dávid; Nagy, Péter R.; Kállay, Mihály

2018-03-01

A reduced-cost implementation of the second-order algebraic-diagrammatic construction [ADC(2)] method is presented. We introduce approximations by restricting virtual natural orbitals and natural auxiliary functions, which results, on average, in more than an order of magnitude speedup compared to conventional, density-fitting ADC(2) algorithms. The present scheme is the successor of our previous approach [D. Mester, P. R. Nagy, and M. Kállay, J. Chem. Phys. 146, 194102 (2017)], which has been successfully applied to obtain singlet excitation energies with the linear-response second-order coupled-cluster singles and doubles model. Here we report further methodological improvements and the extension of the method to compute singlet and triplet ADC(2) excitation energies and transition moments. The various approximations are carefully benchmarked, and conservative truncation thresholds are selected which guarantee errors much smaller than the intrinsic error of the ADC(2) method. Using the canonical values as reference, we find that the mean absolute error for both singlet and triplet ADC(2) excitation energies is 0.02 eV, while that for oscillator strengths is 0.001 a.u. The rigorous cutoff parameters together with the significantly reduced operation count and storage requirements allow us to obtain accurate ADC(2) excitation energies and transition properties using triple-ζ basis sets for systems of up to one hundred atoms.

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.

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.

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.

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.

55-mW, 1.2-V, 12-bit, 100-MSPS Pipeline ADCs for Wireless Receivers

NASA Astrophysics Data System (ADS)

Ito, Tomohiko; Kurose, Daisuke; Ueno, Takeshi; Yamaji, Takafumi; Itakura, Tetsuro

For wireless receivers, low-power 1.2-V 12-bit 100-MSPS pipeline ADCs are fabricated in 90-nm CMOS technology. To achieve low-power dissipation at 1.2V without the degradation of SNR, the configuration of 2.5bit/stage is employed with an I/Q amplifier sharing technique. Furthermore, single-stage pseudo-differential amplifiers are used in a Sample-and-Hold (S/H) circuit and a 1st Multiplying Digital-to-Analog Converter (MDAC). The pseudo-differential amplifier with two-gain-stage transimpedance gain-boosting amplifiers realizes high DC gain of more than 90dB with low power. The measured SNR of the 100-MSPS ADC is 66.7dB at 1.2-V supply. Under that condition, each ADC dissipates only 55mW.

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.

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.

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

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

The correlation between biological activity and diffusion-weighted MR imaging and ADC value in cases with prostate cancer.

PubMed

Sokmen, Bedriye Koyuncu; Sokmen, Dogukan; Ucar, Nese; Ozkurt, Huseyin; Simsek, Abdulmuttalip

2017-12-31

Firstly, we aimed to investigate the correlation among dynamic contrasted magnetic resonance (MR) images, diffusion-weighted MR images, and apparent diffusion coefficent (ADC) values in patients with prostate cancer. Secondly, we aimed to investigate the roles of these variables on clinical risk classification and the biological behavior of the prostate cancer. A total of sixty with prostatic adenocarcinoma patients diagnosed between January 2011 and May 2013 were retrospectively included in the study. Risk classification of patients were evaluated as low-risk (Group 1) (n = 20) (Stage T1c-T2a, PSA < 10 ng/ml, Gleason Score < 7), moderate-risk (Group 2) (n = 18) (Stage T1b-T2c, PSA = 10-20 ng/ml, Gleason Score = 7) and high-risk (Group 3) (n = 22) (Stage > T3a, PSA > 20 ng/ml, Gleason Score > 7). Diffusion-weighted MR images, dynamic contrasted MR images, and ADC values of the prostates were correlated. ADC values of the cases in Group 3 were lower than those of the other groups (p < 0.001). ADC values of the areas without malignancy did not differ significantly between groups (p > 0.05). Biological activity of the tumor tissue was determined by GS, while a negative correlation was observed between GSs and ADC values of the patients, (p < 0.001). In tumors with higher Gleason scores, lower ADC values were obtained. These measured values can play a role in the noninvasive determination of the cellularity of the tumoral mass.

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.

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

PubMed

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

2015-06-01

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

Trade Study of Implementation of Software Defined Radio (SDR): Fundamental Limitations and Future Prospects

DTIC Science & Technology

2008-12-09

as an antenna followed by an analog signal processing chain ( filters , RF amplifiers) followed by an analog-to- digital converter (ADC) followed by a...Figure 2.3 Block diagram of a DSP- based superheterodyne receiver. ADC RF Filter LNA IF Filter IF Amplifier Tunable Local Oscillator ADC...some band limiting filtering and amplification. In a more realistic architecture (Figure 2.3) that we call the DSP- based superheterodyne receiver, a

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

PubMed

Zhou, Nan; Guo, Tingting; Zheng, Huanhuan; Pan, Xia; Chu, Chen; Dou, Xin; Li, Ming; Liu, Song; Zhu, Lijing; Liu, Baorui; Chen, Weibo; He, Jian; Yan, Jing; Zhou, Zhengyang; Yang, Xiaofeng

2017-09-19

We investigated apparent diffusion coefficient (ADC) histogram analysis to evaluate radiation-induced parotid damage and predict xerostomia degrees in nasopharyngeal carcinoma (NPC) patients receiving radiotherapy. The imaging of bilateral parotid glands in NPC patients was conducted 2 weeks before radiotherapy (time point 1), one month after radiotherapy (time point 2), and four months after radiotherapy (time point 3). From time point 1 to 2, parotid volume, skewness, and kurtosis decreased ( P < 0.001, = 0.001, and < 0.001, respectively), but all other ADC histogram parameters increased (all P < 0.001, except P = 0.006 for standard deviation [SD]). From time point 2 to 3, parotid volume continued to decrease ( P = 0.022), and SD, 75 th and 90 th percentiles continued to increase ( P = 0.024, 0.010, and 0.006, respectively). Early change rates of parotid ADC mean , ADC min , kurtosis, and 25 th , 50 th , 75 th , 90 th percentiles (from time point 1 to 2) correlated with late parotid atrophy rate (from time point 1 to 3) (all P < 0.05). Multiple linear regression analysis revealed correlations among parotid volume, time point, and ADC histogram parameters. Early mean change rates for bilateral parotid SD and ADC max could predict late xerostomia degrees at seven months after radiotherapy (three months after time point 3) with AUC of 0.781 and 0.818 ( P = 0.014, 0.005, respectively). ADC histogram parameters were reproducible (intraclass correlation coefficient, 0.830 - 0.999). ADC histogram analysis could be used to evaluate radiation-induced parotid damage noninvasively, and predict late xerostomia degrees of NPC patients treated with radiotherapy.

Spleen magnetic resonance diffusion-weighted imaging for quantitative staging hepatic fibrosis in miniature pigs: An initial study.

PubMed

Chen, Xiao-Li; Chen, Tian-Wu; Zhang, Xiao-Ming; Li, Zhen-Lin; Li, Hang; Zeng, Nan-Lin; Tang, Hong-Jie; Pu, Yu; Chen, Nan; Yang, Qi; Li, Li; Xie, Xian-Yong; Hu, Jiani

2013-11-01

To determine whether spleen diffusion-weighted imaging (DWI) parameters might classify liver fibrosis stage. Sixteen miniature pigs were prospectively used to model liver fibrosis, and underwent spleen DWI by using b = 300, 500 and 800 s/mm(2) on 0, 5th, 9th, 16th and 21st weekend after the beginning of modeling. Signal intensity ratio of spleen to paraspinous muscles (S/M), spleen exponential apparent diffusion coefficient (eADC) and apparent diffusion coefficient (ADC) for each b-value were statistically analyzed. With increasing stages of fibrosis, S/M for all b-values showed a downward trend; and spleen eADC and ADC for b = 300 s/mm(2) showed downward and upward trends, respectively (all P < 0.05). The area under the receiver-operator curve (AUC) of spleen DWI parameters was 0.777 or more by S/M for classifying each fibrosis stage, and 0.65 or more by eADC and 0.648 or more by ADC for classifying stage ≥3 or cirrhosis. Among the spleen DWI parameters, S/M for b = 300 s/mm(2) was the best parameter in classifying stage 1 or more, 2 or more and 3 or more with AUC of 0.875, 0.851 and 0.843, respectively; and spleen eADC for b = 300 s/mm(2) was best in classifying stage 4 with an AUC of 0.988. Spleen DWI may be used to stage liver fibrosis. © 2013 The Japan Society of Hepatology.

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.

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.

The Role of Apparent Diffusion Coefficient Quantification in Differentiating Benign and Malignant Renal Masses by 3 Tesla Magnetic Resonance Imaging.

PubMed

Göya, Cemil; Hamidi, Cihad; Bozkurt, Yaşar; Yavuz, Alpaslan; Kuday, Suzan; Gümüş, Hatice; Türkçü, Gül; Hattapoğlu, Salih; Bilici, Aslan

2015-07-01

Diffusion-weighted magnetic resonance imaging (DWI) is a widely-accepted diagnostic modality whose efficacy has been investigated by numerous past studies in the differentiation of malignant lesions from benign entities. The aim of this study was to evaluate the efficiency of diffusion-weighted magnetic resonance imaging in the characterization of renal lesions. Diagnostic accuracy study. A total of 137 patients with renal lesions were included in this study. The median apparent diffusion coefficient (ADC) values as well as the b 800 and b 1600 signal intensities of normal kidneys, solid components of mixed renal masses, and total cystic lesions were evaluated. There were significant differences between the ADC values of lesions and normal renal parenchyma, and between the ADC values of benign and malignant renal lesions on DWIs at b values of 800 and 1600 s/mm(2) (p<0.001 and p<0.001, respectively). There were significant differences between the ADC values of Bosniak Category 1 and 2 cysts and the ADC values of Bosniak Category 1 and 3 cysts on DWIs at b values of 800 s/mm(2) (p<0.001) and 1600 s/mm(2) (p<0.001). A cutoff value of 1.902 × 10(-3) mm(2)/s for the ADC with a b value of 800 s/mm(2) provided 88% sensitivity and 96% specificity for differentiation between benign and malignant renal lesions. A cutoff value of 1.623 × 10(-3) mm(2)/s for the ADC with a b value of 1600 s/mm(2) provided 79% sensitivity and 96% specificity (p<0.001) for the differentiation between benign and malignant renal lesions. Accurate assessment of renal masses is important for determining the necessity for surgical intervention. DWI provides additional value by differentiating benign from malignant renal tumors and can be added to routine kidney MRI protocols.

Study of the optical properties and the carbonaceous clusters in DAM-ADC solid state nuclear track detectors

NASA Astrophysics Data System (ADS)

Rammah, Y. S.; Abdalla, A. M.

2017-12-01

The optical properties of DAM-ADC solid state nuclear track detectors (SSNTDs) were investigated. Samples of DAM-ADC detector were irradiated at room temperature with gamma doses in the range of 100-500 kGy using 1.25 MeV 60Co source of dose rate 4 kGy/h. The optical characterization of these detectors have been studied through the measurements of UV-visible absorption spectra of blank and γ- irradiated samples. The optical energy band gaps, Eg for the detectors were obtained from the direct and the indirect allowed transitions in K-space using two methods (Tauc's model and absorption spectrum fitting (ASF) method). The absorbance of DAM-ADC detector was found to increase with increasing of the gamma absorbed dose. The width of the tail of localized states in the band gap, Eu was evaluated with the Urbach's method. The number of carbon atoms per conjugated length (N), the number of carbon atoms per cluster (M), and refractive index (n) for the present samples were determined. Both of the direct and the indirect band gaps of DAM-ADC detector decrease with increasing of the gamma absorbed dose. Urbach's energy decreased significantly for the detector. An increase in N, M, and n with increasing of the gamma absorbed dose was noticed. Results shed light on the effect of gamma irradiations of DAM-ADC SSNTDs to suitable industrial applications and to modify the optical properties through gamma-induced modifications of the polymer structure.

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.

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.

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.

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.

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.

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

PubMed

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

2018-05-08

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

Measurement and modeling of diffusion time dependence of apparent diffusion coefficient and fractional anisotropy in prostate tissue ex vivo.

PubMed

Bourne, Roger; Liang, Sisi; Panagiotaki, Eleftheria; Bongers, Andre; Sved, Paul; Watson, Geoffrey

2017-10-01

The purpose of this study was to measure and model the diffusion time dependence of apparent diffusion coefficient (ADC) and fractional anisotropy (FA) derived from conventional prostate diffusion-weighted imaging methods as used in recommended multiparametric MRI protocols. Diffusion tensor imaging (DTI) was performed at 9.4 T with three radical prostatectomy specimens, with diffusion times in the range 10-120 ms and b-values 0-3000 s/mm 2 . ADC and FA were calculated from DTI measurements at b-values of 800 and 1600 s/mm 2 . Independently, a two-component model (restricted isotropic plus Gaussian anisotropic) was used to synthesize DTI data, from which ADC and FA were predicted and compared with the measured values. Measured ADC and FA exhibited a diffusion time dependence, which was closely predicted by the two-component model. ADC decreased by about 0.10-0.15 μm 2 /ms as diffusion time increased from 10 to 120 ms. FA increased with diffusion time at b-values of 800 and 1600 s/mm 2 but was predicted to be independent of diffusion time at b = 3000 s/mm 2 . Both ADC and FA exhibited diffusion time dependence that could be modeled as two unmixed water pools - one having isotropic restricted dynamics, and the other unrestricted anisotropic dynamics. These results highlight the importance of considering and reporting diffusion times in conventional ADC and FA calculations and protocol recommendations, and inform the development of improved diffusion methods for prostate cancer imaging. Copyright © 2017 John Wiley & Sons, Ltd.

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.

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.

Modifications of the optical properties for DAM-ADC nuclear track detector exposed to alpha particles

NASA Astrophysics Data System (ADS)

Rammah, Y. S.; Awad, E. M.

2018-05-01

Modifications of the optical properties of diallyl maleate-allyl diglycol carbonate (DAM-ADC) nuclear detector induced by alpha particles are described. DAM-ADC samples were irradiated perpendicularly by thin 241Am disk source that emits alpha particles with 5.48 MeV. The optical absorption has been measured using the ultraviolet-visible (UV-1100) spectroscopy. It was found that DAM-ADC polymer shows substantial modifications in its optical characteristics upon irradiated with alpha particles with different energies. The optical energy band gap (Egap) for the detector was calculated for the direct and the indirect allowed transitions in K-space using two approaches (Tauc's model and absorption spectrum fitting (ASF) method). Urbach's energy (Ea), number of carbon atoms per conjugated length (N), number of carbon atoms per cluster (M), and refractive index (n) for the present samples were determined. Results reveal that the values of energy gap in direct transition are greater than those of indirect, before and after irradiation. (Egap), (Ea), (N), (M), and (n) of the present samples are changed significantly with irradiation time and value of alpha energy. Results reflect the possibility of using DAM-ADC polymer track detectors to estimate alpha particle energies using the variation of the absorbance.

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

PubMed

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

2012-10-01

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

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.

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

PubMed Central

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

2017-01-01

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

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

PubMed

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

2017-01-01

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

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

McKisson, John

The source code for the Java Data Acquisition suite provides interfaces to the JLab built USB FPGA ADC across a LAN network. Each jDaq node provides ListMode data from JLab built detector systems and readouts.

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

PubMed

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

2008-11-01

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

Apparent diffusion coefficient mapping using diffusion-weighted MRI: impact of background parenchymal enhancement, amount of fibroglandular tissue and menopausal status on breast cancer diagnosis.

PubMed

Horvat, Joao V; Durando, Manuela; Milans, Soledad; Patil, Sujata; Massler, Jessica; Gibbons, Girard; Giri, Dilip; Pinker, Katja; Morris, Elizabeth A; Thakur, Sunitha B

2018-06-01

To investigate the impact of background parenchymal enhancement (BPE), amount of fibroglandular tissue (FGT) and menopausal status on apparent diffusion coefficient (ADC) values in differentiation between malignant and benign lesions. In this HIPAA-compliant study, mean ADC values of 218 malignant and 130 benign lesions from 288 patients were retrospectively evaluated. The differences in mean ADC values between benign and malignant lesions were calculated within groups stratified by BPE level (high/low), amount of FGT (dense/non-dense) and menopausal status (premenopausal/postmenopausal). Sensitivities and specificities for distinguishing malignant from benign lesions within different groups were compared for statistical significance. The mean ADC value for malignant lesions was significantly lower compared to that for benign lesions (1.07±0.21 x 10 -3 mm 2 /s vs. 1.53±0.26 x 10 -3 mm 2 /s) (p<0.0001). Using the optimal cut-off point of 1.30 x 10 -3 mm 2 /s, an area under the curve of 0.918 was obtained, with sensitivity and specificity both of 87 %. There was no statistically significant difference in sensitivities and specificities of ADC values between different groups stratified by BPE level, amount of FGT or menopausal status. Differentiation between benign and malignant lesions on ADC values is not significantly affected by BPE level, amount of FGT or menopausal status. • ADC allows differentiation between benign and malignant lesions. • ADC is useful for breast cancer diagnosis despite different patient characteristics. • BPE, FGT or menopause do not significantly affect sensitivity and specificity.

Diagnostic value of apparent diffusion coefficients to differentiate benign from malignant vertebral bone marrow lesions.

PubMed

Balliu, E; Vilanova, J C; Peláez, I; Puig, J; Remollo, S; Barceló, C; Barceló, J; Pedraza, S

2009-03-01

The aim of this study is to evaluate the value of the apparent diffusion coefficient (ADC) obtained in diffusion-weighted (DW) MR sequences for the differentiation between malignant and benign bone marrow lesions. Forty-five patients with altered signal intensity vertebral bodies on conventional MR sequences were included. The cause of altered signal intensity was benign osteoporotic collapse in 16, acute neoplastic infiltration in 15, and infectious processes in 14; based on plain-film, CT, bone scintigraphy, conventional MR studies, biopsy or follow-up. All patients underwent isotropic DW MR images (multi-shot EPI, b values of 0 and 500 s/mm(2)). Signal intensity at DW MR images was evaluated and ADC values were calculated and compared between malignancy, benign edema and infectious spondylitis. Acute malignant fractures were hyperintense compared to normal vertebral bodies on the diffusion-weighted sequence, except in one patient with sclerotic metastases. Mean ADC value from benign edema (1.9+/-0.39 x 10(-3) mm(2)/s) was significantly (p<0.0001) higher than untreated metastasic lesions (0.9+/-1.3 x 10(-3)mm (2)/s). Mean ADC value of infectious spondilytis (0.96+/-0.49 x 10(-3) mm(2)/s) was not statistically (p>0.05) different from untreated metastasic lesions. ADC value was low (0.75 x 10(-3) mm(2)/s) in one case of subacute benign fracture. ADC values are a useful complementary tool to characterize bone marrow lesions, in order to distinguish acute benign fractures from malignant or infectious bone lesions. However, ADC values are not valuable in order to differentiate malignancy from infection.

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

[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-weighted magnetic resonance imaging of the fetal brain in intrauterine growth restriction.

PubMed

Arthurs, O J; Rega, A; Guimiot, F; Belarbi, N; Rosenblatt, J; Biran, V; Elmaleh, M; Sebag, G; Alison, M

2017-07-01

Diffusion-weighted magnetic resonance imaging (DWI) is a sensitive method for assessing brain maturation and detecting brain lesions, providing apparent diffusion coefficient (ADC) values as a measure of water diffusion. Abnormal ADC values are seen in ischemic brain lesions, such as those associated with acute or chronic hypoxia. The aim of this study was to assess whether ADC values in the fetal brain were different in fetuses with severe intrauterine growth restriction (IUGR) compared with normal controls. Brain magnetic resonance imaging (MRI) with single-shot axial DWI (b = 0 and b = 700 s/mm 2 ) was performed in 30 fetuses with severe IUGR (estimated fetal weight < 3 rd centile with absent or reversed umbilical artery Doppler flow) and in 24 normal controls of similar gestational age. Brain morphology and biometry were analyzed. ADC values were measured in frontal and occipital white matter, centrum semiovale, thalami, cerebellar hemisphere and pons. Frontal-occipital and frontal-cerebellar ADC ratios were calculated, and values were compared between IUGR fetuses and controls. There was no difference in gestational age at MRI between IUGR and control fetuses (IUGR, 30.2 ± 1.6 weeks vs controls, 30.7 ± 1.4 weeks). Fetal brain morphology and signals were normal in all fetuses. Brain dimensions (supratentorial ± infratentorial) were decreased (Z-score, < -2) in 20 (66.7%) IUGR fetuses. Compared with controls, IUGR fetuses had significantly lower ADC values in frontal white matter (1.97 ± 0.23 vs 2.17 ± 0.22 × 10 -3 mm 2 /s; P < 0.0001), thalami (1.04 ± 0.15 vs 1.13 ± 0.10 ×10 -3 mm 2 /s; P = 0.0002), centrum semiovale (1.86 ± 0.22 vs 1.97 ± 0.23 ×10 -3 mm 2 /s; P = 0.01) and pons (0.85 ± 0.19 vs 0.94 ± 0.12 ×10 -3 mm 2 /s; P = 0.043). IUGR fetuses had a lower frontal-occipital ADC ratio than did normal fetuses (1.00 ± 0.11 vs 1.08 ± 0.05; P = 0.003). ADC values in IUGR fetuses were significantly lower than in normal controls in the frontal white matter, thalami, centrum semiovale and pons, suggesting abnormal maturation in these regions. However, the prognostic value of these ADC changes is still unknown. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

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.

Technique of diffusion weighted imaging and its application in stroke

NASA Astrophysics Data System (ADS)

Li, Enzhong; Tian, Jie; Han, Ying; Wang, Huifang; Li, Wu; He, Huiguang

2003-05-01

To study the application of diffusion weighted imaging and image post processing in the diagnosis of stroke, especially in acute stroke, 205 patients were examined by 1.5 T or 1.0 T MRI scanner and the images such as T1, T2 and diffusion weighted images were obtained. Image post processing was done with "3D Med System" developed by our lab to analyze data and acquire the apparent diffusion coefficient (ADC) map. In acute and subacute stage of stroke, the signal in cerebral infarction areas changed to hyperintensity in T2- and diffusion-weighted images, normal or hypointensity in T1-weighted images. In hyperacute stage, however, the signal was hyperintense just in the diffusion weighted imaes; others were normal. In the chronic stage, the signal in T1- and diffusion-weighted imaging showed hypointensity and hyperintensity in T2 weighted imaging. Because ADC declined obviously in acute and subacute stage of stroke, the lesion area was hypointensity in ADC map. With the development of the disease, ADC gradually recovered and then changed to hyperintensity in ADC map in chronic stage. Using diffusion weighted imaging and ADC mapping can make a diagnosis of stroke, especially in the hyperacute stage of stroke, and can differentiate acute and chronic stroke.

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.

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.

Upgrade of BPM Electronics for the SPring-8 Storage Ring

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

Sasaki, Shigeki; Fujita, Takahiro; Shoji, Masazumi

2006-11-20

SPring-8, a 3rd generation synchrotron light source, has operated since 1997. Improvement of BPM performance is required as a part of upgrading activities of the storage ring as a light source. We have developed new electronics circuits for signal processing of the storage ring BPM, with target performance of sub-{mu}m range resolution with sufficiently fast measurement speed and good long-term stability. A set of the new circuits consists of multiplexers, an RF amplifier, a mixer, an IF amplifier, and a local oscillator for analog signal processing. The IF amplifier outputs are sampled with 16-bit 2-MSPS ADC on ADC boards andmore » the data are sent to a DSP board. The sampled data are processed and converted to position information in the DSP. A multiplexing method was employed to have a better stability of the performance by cancellation of variation common to each channel. Evaluation of the performance by using a prototype shows that position resolution well into the sub-{mu}m range has been achieved with a bandwidth of 1 kHz, and long-term stability of within 1 {mu}m has also been achieved.« less

Utility of K-Means clustering algorithm in differentiating apparent diffusion coefficient values between benign and malignant neck pathologies

PubMed Central

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

2014-01-01

Purpose The objective of our study was to analyze the differences between apparent diffusion coefficient (ADC) partitions (created using the K-Means algorithm) between benign and malignant neck lesions and evaluate its benefit in distinguishing these entities. Material and methods MRI studies of 10 benign and 10 malignant proven neck pathologies were post-processed on a PC using in-house software developed in MATLAB (The MathWorks, Inc., Natick, MA). Lesions were manually contoured by two neuroradiologists with the ADC values within each lesion clustered into two (low ADC-ADCL, high ADC-ADCH) and three partitions (ADCL, intermediate ADC-ADCI, ADCH) using the K-Means clustering algorithm. An unpaired two-tailed Student’s t-test was performed for all metrics to determine statistical differences in the means between the benign and malignant pathologies. Results Statistically significant difference between the mean ADCL clusters in benign and malignant pathologies was seen in the 3 cluster models of both readers (p=0.03, 0.022 respectively) and the 2 cluster model of reader 2 (p=0.04) with the other metrics (ADCH, ADCI, whole lesion mean ADC) not revealing any significant differences. Receiver operating characteristics curves demonstrated the quantitative difference in mean ADCH and ADCL in both the 2 and 3 cluster models to be predictive of malignancy (2 clusters: p=0.008, area under curve=0.850, 3 clusters: p=0.01, area under curve=0.825). Conclusion 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 to whole lesion mean ADC alone. PMID:20007723

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.

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

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

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

Correlation between apparent diffusion coefficient and histopathology subtypes of osteosarcoma after neoadjuvant chemotherapy.

PubMed

Wang, Jifei; Sun, Meili; Liu, Dawei; Hu, Xiaoshu; Pui, Margaret H; Meng, Quanfei; Gao, Zhenhua

2017-08-01

Background Neoadjuvant chemotherapy has made limb-salvage surgery possible for the patients with osteosarcoma. Diffusion-weighted magnetic resonance imaging (DWI) has been used to monitor chemotherapy response. Purpose To correlate the apparent diffusion coefficient (ADC) values with histopathology subtypes of osteosarcoma after neoadjuvant chemotherapy. Material and Methods Twelve patients with osteoblastic (n = 7), chondroblastic (n = 4), and fibroblastic (n = 1) osteosarcomas underwent post-chemotherapy DWI before limb-salvage surgery. ADCs corresponding to 127 histological tissue samples from the 12 resected specimens were compared to histological features. Results The mean ADC value of non-cartilaginous viable tumor (38/91, ADC = 1.22 ± 0.03 × 10 -3  mm 2 /s) was significantly ( P < 0.001) lower than that of non-cartilaginous tumor cell necrosis without stroma disintegration (25/91, ADC =1.77 ± 0.03 × 10 -3  mm 2 /s), cartilaginous viable tumor (14/91, ADC = 2.19 ± 0.04 × 10 -3  mm 2 /s), and cystic areas including liquefied necrosis, blood space, and secondary aneurysmal bone cyst (14/91, ADC = 2.29 ± 0.05 × 10 -3  mm 2 /s). The mean ADC value of non-cartilaginous tumor cell necrosis was also significantly ( P < 0.001) smaller than those of viable cartilaginous tumor and cystic/hemorrhagic necrosis whereas the mean ADC values were not significantly ( P > 0.05) different between viable cartilaginous tumor and cystic/hemorrhagic necrosis. Conclusion DWI allows assessment of tumor necrosis after neoadjuvant chemotherapy by ADC differences between viable tumor and necrosis in fibroblastic and osteoblastic osteosarcomas whereas viable chondroblastic osteosarcoma has high ADC and cannot be distinguished reliably from necrosis.

Correlation of 18F-FDG PET and MRI Apparent Diffusion Coefficient Histogram Metrics with Survival in Diffuse Intrinsic Pontine Glioma: A Report from the Pediatric Brain Tumor Consortium.

PubMed

Zukotynski, Katherine A; Vajapeyam, Sridhar; Fahey, Frederic H; Kocak, Mehmet; Brown, Douglas; Ricci, Kelsey I; Onar-Thomas, Arzu; Fouladi, Maryam; Poussaint, Tina Young

2017-08-01

The purpose of this study was to describe baseline 18 F-FDG PET voxel characteristics in pediatric diffuse intrinsic pontine glioma (DIPG) and to correlate these metrics with baseline MRI apparent diffusion coefficient (ADC) histogram metrics, progression-free survival (PFS), and overall survival. Methods: Baseline brain 18 F-FDG PET and MRI scans were obtained in 33 children from Pediatric Brain Tumor Consortium clinical DIPG trials. 18 F-FDG PET images, postgadolinium MR images, and ADC MR images were registered to baseline fluid attenuation inversion recovery MR images. Three-dimensional regions of interest on fluid attenuation inversion recovery MR images and postgadolinium MR images and 18 F-FDG PET and MR ADC histograms were generated. Metrics evaluated included peak number, skewness, and kurtosis. Correlation between PET and MR ADC histogram metrics was evaluated. PET pixel values within the region of interest for each tumor were plotted against MR ADC values. The association of these imaging markers with survival was described. Results: PET histograms were almost always unimodal (94%, vs. 6% bimodal). None of the PET histogram parameters (skewness or kurtosis) had a significant association with PFS, although a higher PET postgadolinium skewness tended toward a less favorable PFS (hazard ratio, 3.48; 95% confidence interval [CI], 0.75-16.28 [ P = 0.11]). There was a significant association between higher MR ADC postgadolinium skewness and shorter PFS (hazard ratio, 2.56; 95% CI, 1.11-5.91 [ P = 0.028]), and there was the suggestion that this also led to shorter overall survival (hazard ratio, 2.18; 95% CI, 0.95-5.04 [ P = 0.067]). Higher MR ADC postgadolinium kurtosis tended toward shorter PFS (hazard ratio, 1.30; 95% CI, 0.98-1.74 [ P = 0.073]). PET and MR ADC pixel values were negatively correlated using the Pearson correlation coefficient. Further, the level of PET and MR ADC correlation was significantly positively associated with PFS; tumors with higher values of ADC-PET correlation had more favorable PFS (hazard ratio, 0.17; 95% CI, 0.03-0.89 [ P = 0.036]), suggesting that a higher level of negative ADC-PET correlation leads to less favorable PFS. A more significant negative correlation may indicate higher-grade elements within the tumor leading to poorer outcomes. Conclusion: 18 F-FDG PET and MR ADC histogram metrics in pediatric DIPG demonstrate different characteristics with often a negative correlation between PET and MR ADC pixel values. A higher negative correlation is associated with a worse PFS, which may indicate higher-grade elements within the tumor. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

Predicting Treatment Response of Colorectal Cancer Liver Metastases to Conventional Lipiodol-Based Transarterial Chemoembolization Using Diffusion-Weighted MR Imaging: Value of Pretreatment Apparent Diffusion Coefficients (ADC) and ADC Changes Under Therapy

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

Lahrsow, Maximilian, E-mail: mlahrsow@gmail.com; Albrecht, Moritz H.; Bickford, Matthew W.

PurposeTo use absolute pretreatment apparent diffusion coefficients (ADC) derived from diffusion-weighted MR imaging (DWI) to predict response to repetitive cTACE for unresectable liver metastases of colorectal carcinoma (CRLM) at 1 and 3 months after start of treatment.Materials and MethodsFifty-five metastases in 34 patients were examined with DWI prior to treatment and 1 month after initial cTACE. Treatment was performed in 4-week intervals. Response was evaluated at 1 and 3 months after start of therapy. Metastases showing a decrease of ≥30% in axial diameter were classified as responding lesions.ResultsOne month after initial cTACE, seven lesions showed early response. There was no significant differencemore » in absolute pretreatment ADC values between responding and non-responding lesions (p = 0.94). Three months after initial cTACE, 17 metastases showed response. There was a significant difference (p = 0.021) between absolute pretreatment ADC values of lesions showing response (median 1.08 × 10{sup −3} mm{sup 2}/s) and no response (median 1.30 × 10{sup −3} mm{sup 2}/s). Pretreatment ADC showed fair diagnostic value to predict response (AUC 0.7). Lesions showing response at 3 months also revealed a significant increase in ADC between measurements before treatment and at one month after initial cTACE (p < 0.001). Applying an increase in ADC of 12.17%, response at 3 months after initial cTACE could be predicted with a sensitivity and specificity of 77 and 74%, respectively (AUC 0.817). Furthermore, there was a strong and significant correlation (r = 0.651, p < 0.001) between percentage change in size after third cTACE and percentage change in ADC.ConclusionIn patients with CRLM, ADC measurements are potential biomarkers for assessing response to cTACE.« less

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.

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.

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

PubMed

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

2016-03-01

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

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.

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.

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.

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.

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.

Cerebral Effects of Targeted Temperature Management Methods Assessed by Diffusion-Weighted Magnetic Resonance Imaging.

PubMed

Grejs, Anders Morten; Gjedsted, Jakob; Pedersen, Michael; Birke-Sørensen, Hanne; Rauff-Mortensen, Andreas; Andersen, Kristian Kjær; Kirkegaard, Hans

2016-12-01

The aim of this randomized porcine study was to compare surface targeted temperature management (TTM) to endovascular TTM evaluated by cerebral diffusion-weighted magnetic resonance imaging (MRI): apparent diffusion coefficient (ADC), and by intracerebral/intramuscular microdialysis. It is well known that alteration in the temperature affects ADC, but the relationship between cerebral ADC values and the cooling method per se has not been established. Eighteen anesthetized 60-kg female swine were hemodynamically and intracerebrally monitored and subsequently subjected to a baseline MRI. The animals were then randomized into three groups: (1) surface cooling (n = 6) at 33.5°C using EMCOOLSpad ® , (2) endovascular cooling (n = 6) at 33.5°C using an Icy ® cooling catheter with the CoolGard 3000 ® , or (3) control (n = 6) at 38.5°C using a Bair Hugger™. The swine were treated with TTM for 6 hours followed by a second MRI examination, including ADC. Blood and microdialysate were sampled regularly throughout the experiment, and glucose, lactate, pyruvate, glycerol, and the lactate/pyruvate ratio did not differ among groups, neither intracerebrally nor intramuscularly. Surface cooling yielded a significantly lower median ADC than endovascular cooling: 714 (634; 804) × 10 -6 mm 2 /s versus 866 (828; 927) × 10 -6 mm 2 /s, (p < 0.05). The surface cooling ADC was lowered to a range usually attributed to cytotoxic edema and these low values could not be explained solely by the temperature effect per se. To what extent the ADC is fully reversible at rewarming is unknown and the clinical implications should be further investigated in clinical studies.

Arithmetic Data Cube as a Data Intensive Benchmark

NASA Technical Reports Server (NTRS)

Frumkin, Michael A.; Shabano, Leonid

2003-01-01

Data movement across computational grids and across memory hierarchy of individual grid machines is known to be a limiting factor for application involving large data sets. In this paper we introduce the Data Cube Operator on an Arithmetic Data Set which we call Arithmetic Data Cube (ADC). We propose to use the ADC to benchmark grid capabilities to handle large distributed data sets. The ADC stresses all levels of grid memory by producing 2d views of an Arithmetic Data Set of d-tuples described by a small number of parameters. We control data intensity of the ADC by controlling the sizes of the views through choice of the tuple parameters.

Multiparametric voxel-based analyses of standardized uptake values and apparent diffusion coefficients of soft-tissue tumours with a positron emission tomography/magnetic resonance system: Preliminary results.

PubMed

Sagiyama, Koji; Watanabe, Yuji; Kamei, Ryotaro; Hong, Sungtak; Kawanami, Satoshi; Matsumoto, Yoshihiro; Honda, Hiroshi

2017-12-01

To investigate the usefulness of voxel-based analysis of standardized uptake values (SUVs) and apparent diffusion coefficients (ADCs) for evaluating soft-tissue tumour malignancy with a PET/MR system. Thirty-five subjects with either ten low/intermediate-grade tumours or 25 high-grade tumours were prospectively enrolled. Zoomed diffusion-weighted and fluorodeoxyglucose ( 18 FDG)-PET images were acquired along with fat-suppressed T2-weighted images (FST2WIs). Regions of interest (ROIs) were drawn on FST2WIs including the tumour in all slices. ROIs were pasted onto PET and ADC-maps to measure SUVs and ADCs within tumour ROIs. Tumour volume, SUVmax, ADCminimum, the heterogeneity and the correlation coefficients of SUV and ADC were recorded. The parameters of high- and low/intermediate-grade groups were compared, and receiver operating characteristic (ROC) analysis was also performed. The mean correlation coefficient for SUV and ADC in high-grade sarcomas was lower than that of low/intermediate-grade tumours (-0.41 ± 0.25 vs. -0.08 ± 0.34, P < 0.01). Other parameters did not differ significantly. ROC analysis demonstrated that correlation coefficient showed the best diagnostic performance for differentiating the two groups (AUC 0.79, sensitivity 96.0%, specificity 60%, accuracy 85.7%). SUV and ADC determined via PET/MR may be useful for differentiating between high-grade and low/intermediate-grade soft tissue tumours. • PET/MR allows voxel-based comparison of SUVs and ADCs in soft-tissue tumours. • A comprehensive assessment of internal heterogeneity was performed with scatter plots. • SUVmax or ADCminimum could not differentiate high-grade sarcoma from low/intermediate-grade tumours. • Only the correlation coefficient between SUV and ADC differentiated the two groups. • The correlation coefficient showed the best diagnostic performance by ROC analysis.

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

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.

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

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.

Resonant Tunneling Analog-To-Digital Converter

NASA Technical Reports Server (NTRS)

Broekaert, T. P. E.; Seabaugh, A. C.; Hellums, J.; Taddiken, A.; Tang, H.; Teng, J.; vanderWagt, J. P. A.

1995-01-01

As sampling rates continue to increase, current analog-to-digital converter (ADC) device technologies will soon reach a practical resolution limit. This limit will most profoundly effect satellite and military systems used, for example, for electronic countermeasures, electronic and signal intelligence, and phased array radar. New device and circuit concepts will be essential for continued progress. We describe a novel, folded architecture ADC which could enable a technological discontinuity in ADC performance. The converter technology is based on the integration of multiple resonant tunneling diodes (RTD) and hetero-junction transistors on an indium phosphide substrate. The RTD consists of a layered semiconductor hetero-structure AlAs/InGaAs/AlAs(2/4/2 nm) clad on either side by heavily doped InGaAs contact layers. Compact quantizers based around the RTD offer a reduction in the number of components and a reduction in the input capacitance Because the component count and capacitance scale with the number of bits N, rather than by 2 (exp n) as in the flash ADC, speed can be significantly increased, A 4-bit 2-GSps quantizer circuit is under development to evaluate the performance potential. Circuit designs for ADC conversion with a resolution of 6-bits at 25GSps may be enabled by the resonant tunneling approach.

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.

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.

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

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

PubMed

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

2009-01-01

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

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

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.

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

PubMed

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

2015-09-01

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

Hyperpolarized 3He and 129Xe magnetic resonance imaging apparent diffusion coefficients: physiological relevance in older never‐ and ex‐smokers

PubMed Central

Kirby, Miranda; Ouriadov, Alexei; Svenningsen, Sarah; Owrangi, Amir; Wheatley, Andrew; Etemad‐Rezai, Roya; Santyr, Giles E.; McCormack, David G.; Parraga, Grace

2014-01-01

Abstract Noble gas pulmonary magnetic resonance imaging (MRI) is transitioning away from 3He to 129Xe gas, but the physiological/clinical relevance of 129Xe apparent diffusion coefficient (ADC) parenchyma measurements is not well understood. Therefore, our objective was to generate 129Xe MRI ADC for comparison with 3He ADC and with well‐established measurements of alveolar structure and function in older never‐smokers and ex‐smokers with chronic obstructive pulmonary disease (COPD). In four never‐smokers and 10 COPD ex‐smokers, 3He (b = 1.6 sec/cm2) and 129Xe (b = 12, 20, and 30 sec/cm2) ADC, computed tomography (CT) density‐threshold measurements, and the diffusing capacity for carbon monoxide (DLCO) were measured. To understand regional differences, the anterior–posterior (APG) and superior–inferior (∆SI) ADC differences were evaluated. Compared to never‐smokers, COPD ex‐smokers showed greater 3He ADC (P = 0.006), 129Xe ADCb12 (P = 0.006), and ADCb20 (P = 0.006), but not for ADCb30 (P > 0.05). Never‐smokers and COPD ex‐smokers had significantly different APG for 3He ADC (P = 0.02), 129Xe ADCb12 (P = 0.006), and ADCb20 (P = 0.01), but not for ADCb30 (P > 0.05). ∆SI for never‐ and ex‐smokers was significantly different for 3He ADC (P = 0.046), but not for 129Xe ADC (P > 0.05). There were strong correlations for DLCO with 3He ADC and 129Xe ADCb12 (both r = −0.95, P < 0.05); in a multivariate model 129Xe ADCb12 was the only significant predictor of DLCO (P = 0.049). For COPD ex‐smokers, CT relative area <−950 HU (RA950) correlated with 3He ADC (r = 0.90, P = 0.008) and 129Xe ADCb12 (r = 0.85, P = 0.03). In conclusion, while 129Xe ADCb30 may be appropriate for evaluating subclinical or mild emphysema, in this small group of never‐smokers and ex‐smokers with moderate‐to‐severe emphysema, 129Xe ADCb12 provided a physiologically appropriate estimate of gas exchange abnormalities and alveolar microstructure. PMID:25347853

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.

Pilot Study of the Use of Hybrid Multidimensional T2-Weighted Imaging-DWI for the Diagnosis of Prostate Cancer and Evaluation of Gleason Score.

PubMed

Sadinski, Meredith; Karczmar, Gregory; Peng, Yahui; Wang, Shiyang; Jiang, Yulei; Medved, Milica; Yousuf, Ambereen; Antic, Tatjana; Oto, Aytekin

2016-09-01

The objective of our study was to evaluate the role of a hybrid T2-weighted imaging-DWI sequence for prostate cancer diagnosis and differentiation of aggressive prostate cancer from nonaggressive prostate cancer. Twenty-one patients with prostate cancer who underwent preoperative 3-T MRI and prostatectomy were included in this study. Patients underwent a hybrid T2-weighted imaging-DWI examination consisting of DW images acquired with TEs of 47, 75, and 100 ms and b values of 0 and 750 s/mm(2). The apparent diffusion coefficient (ADC) and T2 were calculated for cancer and normal prostate ROIs at each TE and b value. Changes in ADC and T2 as a function of increasing the TE and b value, respectively, were analyzed. A new metric termed "PQ4" was defined as the percentage of voxels within an ROI that has increasing T2 with increasing b value and has decreasing ADC with increasing TE. ADC values were significantly higher in normal ROIs than in cancer ROIs at all TEs (p < 0.0001). With increasing TE, the mean ADC increased 3% in cancer ROIs and increased 12% in normal ROIs. T2 was significantly higher in normal ROIs than in cancer ROIs at both b values (p ≤ 0.0002). The mean T2 decreased with increasing b value in cancer ROIs (ΔT2 = -17 ms) and normal ROIs (ΔT2 = -52 ms). PQ4 clearly differentiated normal ROIs from prostate cancer ROIs (p = 0.0004) and showed significant correlation with Gleason score (ρ = 0.508, p < 0.0001). Hybrid MRI measures the response of ADC and T2 to changing TEs and b values, respectively. This approach shows promise for detecting prostate cancer and determining its aggressiveness noninvasively.

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.

Microstructural effects of Ramadan fasting on the brain: a diffusion tensor imaging study.

PubMed

Bakan, Ayse Ahsen; Yıldız, Seyma; Alkan, Alpay; Yetis, Huseyin; Kurtcan, Serpil; Ilhan, Mahmut Muzaffer

2015-01-01

We aimed to examine whether the brain displays any microstructural changes after a three-week Ramadan fasting period using diffusion tenson imaging. This study included a study and a control group of 25 volunteers each. In the study group, we examined and compared apparent diffusion coefficient (ADC) and fractional anisotropy (FA) values of the participants during (phase 1) and after (phase 2) a period of fasting. The control group included individuals who did not fast. ADC and FA values obtained in phase 1 and phase 2 were compared between the study and control groups. In the study group, ADC values of hypothalamus and, to a lesser extent, of insula were lower in phase 1 compared with phase 2 and the control group. The FA values of amygdala, middle temporal cortex, thalamus and, to a lesser extent, of medial prefrontal cortex were lower in phase 1 compared with phase 2 and the control group. Phase 2 ADC and FA values of the study group were not significantly different compared with the control group at any brain location. A three-week Ramadan fasting period can cause microstructural changes in the brain, and diffusion tensor imaging enables the visualization of these changes. The identification of brain locations where changes occurred in ADC and FA values during fasting can be helpful in diagnostic imaging and understanding the pathophysiology of eating disorders.

Microstructural effects of Ramadan fasting on the brain: a diffusion tensor imaging study

PubMed Central

Bakan, Ayse Ahsen; Yıldız, Seyma; Alkan, Alpay; Yetis, Huseyin; Kurtcan, Serpil; Ilhan, Mahmut Muzaffer

2015-01-01

PURPOSE We aimed to examine whether the brain displays any microstructural changes after a three-week Ramadan fasting period using diffusion tenson imaging. METHODS This study included a study and a control group of 25 volunteers each. In the study group, we examined and compared apparent diffusion coefficient (ADC) and fractional anisotropy (FA) values of the participants during (phase 1) and after (phase 2) a period of fasting. The control group included individuals who did not fast. ADC and FA values obtained in phase 1 and phase 2 were compared between the study and control groups. RESULTS In the study group, ADC values of hypothalamus and, to a lesser extent, of insula were lower in phase 1 compared with phase 2 and the control group. The FA values of amygdala, middle temporal cortex, thalamus and, to a lesser extent, of medial prefrontal cortex were lower in phase 1 compared with phase 2 and the control group. Phase 2 ADC and FA values of the study group were not significantly different compared with the control group at any brain location. CONCLUSION A three-week Ramadan fasting period can cause microstructural changes in the brain, and diffusion tensor imaging enables the visualization of these changes. The identification of brain locations where changes occurred in ADC and FA values during fasting can be helpful in diagnostic imaging and understanding the pathophysiology of eating disorders. PMID:25835077

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.

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

Characteristics of ADC12/nano Al2O3composites with Addition of Ti Produced By Stir Casting Method

NASA Astrophysics Data System (ADS)

Zulfia, A.; Krisiphala; Ferdian, D.; Utomo, B. W.; Dhaneswara, D.

2018-03-01

The mechanical properties and microstructure of ADC12/nano Al2O3 matrix composites have been studied in this work. The composites were produced by stir casting method. ADC 12 as matrix composites was combined by Mg and Ti. The addition of Ti was varied from 0.02 to 0.08 wt-% as grain refinement wetting to improve mechanical properties such as tensile strength, hardness and wear resistance, while Mg addition was to promote wetting between ADC 12 and nano Al2O3. The optimum tensile strength was found at 0.04 wt-% addition of Ti with value of 132.5 MPa, further adding more Ti cause a poisoning mechanism that will hindered the grain refining process and reduce the tensile strength. The hardness and wear resistance of composites would also increase because of the refinement process. and the added Magnesium in the material that will form Mg2Si primary phases who have a high hardness value.

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.

The target invites a foe: antibody-drug conjugates in gynecologic oncology.

PubMed

Campos, Maira P; Konecny, Gottfried E

2018-02-01

Antibody-drug conjugates (ADCs) represent a promising new class of cancer therapeutics. Currently more than 60 ADCs are in clinical development, however, only very few trials focus on gynecologic malignancies. In this review, we summarize the most recent advances in ADC drug development with an emphasis on how this progress relates to patients diagnosed with gynecologic malignancies and breast cancer. The cytotoxic payloads of the majority of the ADCs that are currently in clinical trials for gynecologic malignancies or breast cancer are auristatins (MMAE, MMAF), maytansinoids (DM1, DM4), calicheamicin, pyrrolobenzodiazepines and SN-38. Both cleavable and noncleavable linkers are currently being investigated in clinical trials. A number of novel target antigens are currently being validated in ongoing clinical trials including folate receptor alpha, mesothelin, CA-125, NaPi2b, NOTCH3, protein tyrosine kinase-like 7, ephrin-A4, TROP2, CEACAM5, and LAMP1. For most ADCs currently in clinical development, dose-limiting toxicities appear to be unrelated to the targeted antigen but more tightly associated with the payload. Rational drug design involving optimization of the antibody, the linker and the conjugation chemistry is aimed at improving the therapeutic index of new ADCs. Antibody-drug conjugates can increase the efficacy and decrease the toxicity of their payloads in comparison with traditional cyctotoxic agents. A better and quicker translation of recent scientific advances in the field of ADCs into rational clinical trials for patients diagnosed with ovarian, endometrial or cervical cancer could create real improvements in tumor response, survival and quality of life for our patients.

Antibody-Drug Conjugates (ADCs) for Personalized Treatment of Solid Tumors: A Review.

PubMed

Lambert, John M; Morris, Charles Q

2017-05-01

Attaching a cytotoxic "payload" to an antibody to form an antibody-drug conjugate (ADC) provides a mechanism for selective delivery of the cytotoxic agent to cancer cells via the specific binding of the antibody to cancer-selective cell surface molecules. The first ADC to receive marketing authorization was gemtuzumab ozogamicin, which comprises an anti-CD33 antibody conjugated to a highly potent DNA-targeting antibiotic, calicheamicin, approved in 2000 for treating acute myeloid leukemia. It was withdrawn from the US market in 2010 following an unsuccessful confirmatory trial. The development of two classes of highly potent microtubule-disrupting agents, maytansinoids and auristatins, as payloads for ADCs resulted in approval of brentuximab vedotin in 2011 for treating Hodgkin lymphoma and anaplastic large cell lymphoma, and approval of ado-trastuzumab emtansine in 2013 for treating HER2-positive breast cancer. Their success stimulated much research into the ADC approach, with >60 ADCs currently in clinical evaluation, mostly targeting solid tumors. Five ADCs have advanced into pivotal clinical trials for treating various solid tumors-platinum-resistant ovarian cancer, mesothelioma, triple-negative breast cancer, glioblastoma, and small cell lung cancer. The level of target expression is a key parameter in predicting the likelihood of patient benefit for all these ADCs, as well as for the approved compound, ado-trastuzumab emtansine. The development of a patient selection strategy linked to target expression on the tumor is thus critically important for identifying the population appropriate for receiving treatment.

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.

Evaluation of Multi-Channel ADCs for Gamma-Ray Spectroscopy

NASA Astrophysics Data System (ADS)

Tan, Hui; Hennig, Wolfgang; Walby, Mark D.; Breus, Dimitry; Harris, Jackson

2013-04-01

As nuclear physicists increasingly design large scale experiments with hundreds or thousands of detector channels, there are growing needs for high density readout electronics with good timing and energy resolution that at the same time offer lower cost per channel compared to existing commercial solutions. Recent improvements in the design of commercial analog to digital converters (ADCs) have resulted in a variety of multi-channel ADCs that are natural choice for designing such high density readout modules. However, multi-channel ADCs typically are designed for medical imaging/ultrasound applications and therefore are not rated for their spectroscopic characteristics. In this work, we evaluated the gamma-ray spectroscopic performance of several multi-channel ADCs, including their energy resolution, nonlinearity, and timing resolution. Some of these ADCs demonstrated excellent energy resolution, 2.66% FWHM at 662 keV with a LaBr3 or 1.78 keV FWHM at 1332.5 keV with a high purity germanium (HPGe) detector, and sub-nanosecond timing resolution with LaBr 3. We present results from these measurements to illustrate their suitability for gamma-ray spectroscopy.

WE-G-BRD-01: Diffusion Weighted MRI for Response Assessment of Inoperable Lung Tumors for Patients Undergoing SBRT Treatment

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

Tyagi, N; Wengler, K; Yorke, E

2014-06-15

Purpose: To investigate early changes in tumor Apparent Diffusion Coefficients derived from diffusion weighted (DW)-MRI of lung cancer patients undergoing SBRT, as a possible early predictor of treatment response. Methods: DW-MRI scans were performed in this prospective phase I IRB-approved study of inoperable lung tumors at various time-points during the course of SBRT treatments. Axial DW scan using multi b-values ranging from 0–1000 s/mm{sup 2} were acquired in treatment position on a 3T Philips MR scanner during simulation, one hour after the first fraction (8 Gy), after a total of 5 fractions (40 Gy) and 4 weeks after SBRT delivery.more » A monoexponential model based on a least square fit from all b values was performed on a pixel-by-pixel basis and ADC was calculated. GTVs drawn on 4DCT for planning were mapped on the T2w MRI (acquired at exhale) after deformable registration. These volumes were then mapped on DWI scan for ADC calculation after rigid registration between the anatomical scan and diffusion scan. T2w scan on followup time points were deformably registered to the pretreatment T2 scan. Results: The first two patients in this study were analyzed. Median ADC values were 1.48, 1.48, 1.62 and 1.83 (10{sup −3}×) mm{sup 2}/s at pretreatment, after 8 Gy, after 40 Gy and 4 weeks posttreatment for the first patient and 1.57, 1.53, 1.66 and 1.72 (10{sup −3}×) mm{sup 2}/s for the second patient. ADC increased more significantly after 4 weeks of treatment rather than immediately post treatment, implying that late ADC value may be a better predictor of tumor response for SBRT treatment. The fraction of tumor pixels at high ADC values increased at 4 weeks post treatment. Conclusion: The observed increase in ADC values before the end of radiotherapy may be a surrogate for tumor response, but further patient accrual will be necessary to determine its value.« less

Assessment of mediastinal tumors with diffusion-weighted single-shot echo-planar MRI.

PubMed

Razek, Ahmed Abdel; Elmorsy, Ahmed; Elshafey, Mohsen; Elhadedy, Tamer; Hamza, Osama

2009-09-01

To assess the role of diffusion-weighted single-shot echo-planar magnetic resonance imaging (MRI) in patients with mediastinal tumors. Prospective study was conducted on 45 consecutive patients (29 male, 16 female, age 22-66 years, mean 41 years) with mediastinal tumor. They underwent diffusion-weighted single-shot echo-planar MRI of the mediastinum with a b-factor of 0, 300, and 600 sec/mm(2). The apparent diffusion coefficient (ADC) value of the mediastinal tumor was correlated with the histopathological findings. The mean ADC value of malignant mediastinal tumors was 1.09 +/- 0.25 x 10(-3) mm(2)/sec, and of benign tumors was 2.38 +/- 0.56 x 10(-3) mm(2)/sec. There was a significant difference in the mean ADC value between malignant and benign tumors (P = 0.001) and within different grades of malignancy (0.001). When an ADC value of 1.56 x 10(-3) mm(2)/sec was used as a threshold value for differentiating malignant from benign tumor, the best results were obtained with an accuracy of 95%, sensitivity of 96%, specificity of 94%, positive predictive value of 94%, negative predictive value of 96%, and area under the curve of 0.938. The ADC value is a noninvasive parameter that can be used for differentiation of malignant from benign mediastinal tumors and grading of mediastinal malignancy.

In-pixel conversion with a 10 bit SAR ADC for next generation X-ray FELs

NASA Astrophysics Data System (ADS)

Lodola, L.; Batignani, G.; Benkechkache, M. A.; Bettarini, S.; Casarosa, G.; Comotti, D.; Dalla Betta, G. F.; Fabris, L.; Forti, F.; Grassi, M.; Latreche, S.; Malcovati, P.; Manghisoni, M.; Mendicino, R.; Morsani, F.; Paladino, A.; Pancheri, L.; Paoloni, E.; Ratti, L.; Re, V.; Rizzo, G.; Traversi, G.; Vacchi, C.; Verzellesi, G.; Xu, H.

2016-07-01

This work presents the design of an interleaved Successive Approximation Register (SAR) ADC, part of the readout channel for the PixFEL detector. The PixFEL project aims at substantially advancing the state-of-the-art in the field of 2D X-ray imaging for applications at the next generation Free Electron Laser (FEL) facilities. For this purpose, the collaboration is developing the fundamental microelectronic building blocks for the readout channel. This work focuses on the design of the ADC carried out in a 65 nm CMOS technology. To obtain a good tradeoff between power consumption, conversion speed and area occupation, an interleaved SAR ADC architecture was adopted.

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.

A SAR-ADC using unit bridge capacitor and with calibration for the front-end electronics of PET imaging

NASA Astrophysics Data System (ADS)

Liu, Wei; Wei, Tingcun; Li, Bo; Yang, Lifeng; Xue, Feifei; Hu, Yongcai

2016-05-01

This paper presents a 12-bit 1 MS/s successive approximation register-analog to digital converter (SAR-ADC) for the 32-channel front-end electronics of CZT-based PET imaging system. To reduce the capacitance mismatch, instead of the fractional capacitor, the unit capacitor is used as the bridge capacitor in the split-capacitor digital to analog converter (DAC) circuit. In addition, in order to eliminate the periodical DNL errors of -1 LSB which often exists in the SAR-ADC using the charge-redistributed DAC, a calibration algorithm is proposed and verified by the experiments. The proposed 12-bit 1 MS/s SAR-ADC is designed and implemented using a 0.35 μm CMOS technology, it occupies only an active area of 986×956 μm2. The measurement results show that, at the power supply of 3.3/5.0 V and the sampling rate of 1 MS/s, the ADC with calibration has a signal-to-noise-and-distortion ratio (SINAD) of 67.98 dB, the power dissipation of 5 mW, and a figure of merit (FOM) of 2.44 pJ/conv.-step. This ADC is with the features of high accuracy, low power and small layout area, it is especially suitable to the one-chip integration of the front-end readout electronics.

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.

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.

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

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

Diffusion-Weighted MRI Assessment of Adjacent Disc Degeneration After Thoracolumbar Vertebral Fractures

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

Noriega, David C., E-mail: dcnoriega1970@gmail.com; Marcia, Stefano, E-mail: stemarcia@gmail.com; Ardura, Francisco, E-mail: fardura@ono.com

ObjectiveThe purpose of this study was to assess, by the mean apparent diffusion coefficient (ADC), if a relationship exists between disc ADC and MR findings of adjacent disc degeneration after thoracolumbar fractures treated by anatomic reduction using vertebral augmentation (VAP).Materials and MethodsTwenty non-consecutive patients (mean age 50.7 years; range 45–56) treated because of vertebral fractures, were included in this study. There were 10 A3.1 and 10 A1.2 fractures (AO classification). Surgical treatment using VAP was applied in 14 cases, and conservative in 6 patients. MRI T2-weighted images and mapping of apparent diffusion coefficient (ADC) of the intervertebral disc adjacent to themore » fractured segment were performed after a mean follow-up of 32 months. A total of 60 discs, 3 per patient, were analysed: infra-adjacent, supra-adjacent and a control disc one level above the supra-adjacent.ResultsNo differences between patients surgically treated and those following a conservative protocol regarding the average ADC values obtained in the 20 control discs analysed were found. Considering all discs, average ADC in the supra-adjacent level was lower than in the infra-adjacent (1.35 ± 0.12 vs. 1.53 ± 0.06; p < 0.001). Average ADC values of the discs used as a control were similar to those of the infra-adjacent level (1.54 ± 0.06). Compared to surgically treated patients, discs at the supra-adjacent fracture level showed statistically significant lower values in cases treated conservatively (p < 0.001). The variation in the delay of surgery had no influence on the average values of ADC at any of the measured levels.ConclusionsADC measurements of the supra-adjacent discs after a mean follow-up of 32 months following thoracolumbar fractures, showed that restoration of the vertebral collapse by minimally invasive VAP prevents posttraumatic disc degeneration.« less

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.

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.

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

Predicting postnatal renal function of prenatally detected posterior urethral valves using fetal diffusion-weighted magnetic resonance imaging with apparent diffusion coefficient determination.

PubMed

Faure, Alice; Panait, Nicoleta; Panuel, Michel; Alessandrini, Pierre; D'Ercole, Claude; Chaumoitre, Kathia; Merrot, Thierry

2017-07-01

The objective of this study was to evaluate the accuracy of fetal diffusion-weighted magnetic resonance imaging with apparent diffusion coefficient (ADC) determination to predict postnatal renal function (nadir creatinine at 1 year and eGFR) of men with posterior urethral valves (PUV). Between 2003 and 2014, 11 MRI were performed on fetuses (between 28 and 32 weeks) in whom second trimester sonography suggested severe bilateral urinary tract anomalies, suspected of PUV. The ADC of the 11 fetuses ranged from 1.3 to 2.86 mm 2  s -1 (median = 1.79 mm 2  s -1 , normal range for fetal kidney: 1.1-1.8). Two pregnancies with ADC > 2.6 mm 2  s -1 were interrupted; the autopsy confirmed PUV and Potter syndrome. For the remaining nine babies, the follow-up was 5.4 years (0.8-10). Four children with abnormal ADC (1.8-2.3) had chronic kidney disease. The remaining five cases with normal nadir creatinine and eGFR had normal ADC. One case with unilateral elevated ADC had a poor ipsilateral renal function on dimercaptosuccinic acid scan. Here, it seems that diffusion-weighted magnetic resonance imaging with ADC determination could be useful in accurately evaluating fetal kidneys in PUV and predicting renal function. It may be an additional, non-invasive method when biologic and sonographic findings are inconclusive, especially in the case of oligohydramnios. Further studies are needed to confirm our data. © 2017 John Wiley & Sons, Ltd. © 2017 John Wiley & Sons, Ltd.

Quantitative liver ADC measurements using diffusion-weighted MRI at 3 Tesla: evaluation of reproducibility and perfusion dependence using different techniques for respiratory compensation.

PubMed

Larsen, Nis Elbrønd; Haack, Søren; Larsen, Lars Peter Skovgaard; Pedersen, Erik Morre

2013-10-01

Diffusion weighted imaging (DWI) of the liver suffers from low signal to noise making 3 Tesla (3 T) an attractive option, but 3 T data is scarce. It was the aim to study the influence of different b values and respiratory compensation methods (RCM) on the apparent diffusion coefficient (ADC) level and on ADC reproducibility at 3 T. Ten healthy volunteers and 12 patients with malignant liver lesions underwent repeated (2-22 days) breathhold, free-breathing and respiratory triggered DWI at 3 T using b values between 0 and 1,000 s/mm(2). The ADCs changed up to 150% in healthy livers and up to 48% in malignant lesions depending on b value combinations. Best ADC reproducibility in healthy livers were obtained with respiratory triggering (95% limits of agreement: ±0.12) and free-breathing (±0.14). In malignant lesions equivalent reproducibility was obtained with less RCM dependence. The use of a lower maximum b value (b = 500) decreased reproducibility (±0.14 to ±0.32) in both normal liver and malignant lesions. Large differences in absolute ADC values and reproducibility caused by varying combinations of clinically realistic b values were demonstrated. Different RCMs caused smaller differences. Lowering maximum b value to 500 increased limits of agreement up to a factor of two. Serial ADC changes larger than approximately 15% can be detected confidently on an individual basis in both malignant lesions and normal liver parenchyma at 3 T using appropriate b values and respiratory compensation.

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

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.

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

PubMed

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

2012-10-01

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

JOURNAL CLUB: The Warthin Tumor Score: A Simple and Reliable Method to Distinguish Warthin Tumors From Pleomorphic Adenomas and Carcinomas.

PubMed

Wang, Chih-Wei; Chu, Yueng-Hsiang; Chiu, Deng-Yiv; Shin, Nieh; Hsu, Hsian-He; Lee, Jih-Chin; Juan, Chun-Jung

2018-06-01

The objective of this article is to propose a Warthin tumor (WT) score to distinguish WTs from other parotid tumors. The study included 78 patients with 92 histologically proven parotid tumors, including 42 WTs, 30 pleomorphic adenomas (PMAs), and 20 carcinomas. Echo-planar DW images were acquired. The WT score, which comprised the mean apparent diffusion coefficient (ADC M ) and the SD of the ADC (ADC SD ) of tumors, patient age, and patient sex, was used to predict WTs. The diagnostic performance of the WT score was evaluated using ROC analyses. Statistical significance was denoted by p < 0.05. With the use of optimized criteria, including an ADC M less than or equal to 1.016 × 10 -3 mm 2 /s (WT score, 1), an ADC SD less than or equal to 0.1171 × 10 -3 mm 2 /s (WT score, 1), patient age older than 49 years (WT score, 1), and male sex (WT score, 1), a WT score greater than 2 had a sensitivity, specificity, positive negative value, negative predictive value, and accuracy of 85.7%, 100.0%, 100.0%, 89.3%, and 93.4%, respectively. The WT score allows parotid WTs to be distinguished from PMAs and carcinomas with high accuracy.

Design and characterization of a 12-bit 10MS/s 10mW pipelined SAR ADC for CZT-based hard X-ray imager

NASA Astrophysics Data System (ADS)

Xue, F.; Gao, W.; Duan, Y.; Zheng, R.; Hu, Y.

2018-02-01

This paper presents a 12-bit pipelined successive approximation register (SAR) ADC for CZT-based hard X-ray Imager. The proposed ADC is comprised of a first-stage 6-bit SAR-based Multiplying Digital Analog Converter (MDAC) and a second-stage 8-bit SAR ADC. A novel MDAC architecture using Vcm-based Switching method is employed to maximize the energy efficiency and improve the linearity of the ADC. Moreover, the unit-capacitor array instead of the binary-weighted capacitor array is adopted to improve the conversion speed and linearity of the ADC in the first-stage MDAC. In addition, a new layout design method for the binary-weighted capacitor array is proposed to reduce the capacitor mismatches and make the routing become easier and less-time-consuming. Finally, several radiation-hardened-by-design technologies are adopted in the layout design against space radiation effects. The prototype chip was fabricated in 0.18 μm mixed-signal 1.8V/3.3V process and operated at 1.8 V supply. The chip occupies a core area of only 0.58 mm2. The proposed pipelined SAR ADC achieves a peak signal-to-noise-and-distortion ratio (SNDR) of 66.7 dB and a peak spurious-free dynamic range (SFDR) of 78.6 dB at 10 MS/s sampling rate and consumes 10 mW. The figure of merit (FOM) of the proposed ADC is 0.56 pJ/conversion-step.

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.

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.

Mis-estimation and bias of hyperpolarized apparent diffusion coefficient measurements due to slice profile effects.

PubMed

Gordon, Jeremy W; Milshteyn, Eugene; Marco-Rius, Irene; Ohliger, Michael; Vigneron, Daniel B; Larson, Peder E Z

2017-09-01

The purpose of this work was to explore the impact of slice profile effects on apparent diffusion coefficient (ADC) mapping of hyperpolarized (HP) substrates. Slice profile effects were simulated using a Gaussian radiofrequency (RF) pulse with a variety of flip angle schedules and b-value ordering schemes. A long T 1 water phantom was used to validate the simulation results, and ADC mapping of HP [ 13 C, 15 N 2 ]urea was performed on the murine liver to assess these effects in vivo. Slice profile effects result in excess signal after repeated RF pulses, causing bias in HP measurements. The largest error occurs for metabolites with small ADCs, resulting in up to 10-fold overestimation for metabolites that are in more-restricted environments. A mixed b-value scheme substantially reduces this bias, whereas scaling the slice-select gradient can mitigate it completely. In vivo, the liver ADC of hyperpolarized [ 13 C, 15 N 2 ]urea is nearly 70% lower (0.99 ± 0.22 vs 1.69 ± 0.21 × 10 -3 mm 2 /s) when slice-select gradient scaling is used. Slice profile effects can lead to bias in HP ADC measurements. A mixed b-value ordering scheme can reduce this bias compared to sequential b-value ordering. Slice-select gradient scaling can also correct for this deviation, minimizing bias and providing more-precise ADC measurements of HP substrates. Magn Reson Med 78:1087-1092, 2017. © 2016 International Society for Magnetic Resonance in Medicine. © 2016 International Society for Magnetic Resonance in Medicine.

Diffusion-weighted magnetic resonance imaging for assessment of lung lesions: repeatability of the apparent diffusion coefficient measurement.

PubMed

Bernardin, L; Douglas, N H M; Collins, D J; Giles, S L; O'Flynn, E A M; Orton, M; deSouza, N M

2014-02-01

To establish repeatability of apparent diffusion coefficients (ADCs) acquired from free-breathing diffusion-weighted magnetic resonance imaging (DW-MRI) in malignant lung lesions and investigate effects of lesion size, location and respiratory motion. Thirty-six malignant lung lesions (eight patients) were examined twice (1- to 5-h interval) using T1-weighted, T2-weighted and axial single-shot echo-planar DW-MRI (b = 100, 500, 800 s/mm(2)) during free-breathing. Regions of interest around target lesions on computed b = 800 s/mm(2) images by two independent observers yielded ADC values from maps (pixel-by-pixel fitting using all b values and a mono-exponential decay model). Intra- and inter-observer repeatability was assessed per lesion, per patient and by lesion size (> or <2 cm) or location. ADCs were similar between observers (mean ± SD, 1.15 ± 0.28 × 10(-3) mm(2)/s, observer 1; 1.15 ± 0.29 × 10(-3) mm(2)/s, observer 2). Intra-observer coefficients of variation of the mean [median] ADC per lesion and per patient were 11% [11.4%], 5.7% [5.7%] for observer 1 and 9.2% [9.5%], 3.9% [4.7%] for observer 2 respectively; inter-observer values were 8.9% [9.3%] (per lesion) and 3.0% [3.7%] (per patient). Inter-observer coefficient of variation (CoV) was greater for lesions <2 cm (n = 20) compared with >2 cm (n = 16) (10.8% vs 6.5% ADCmean, 11.3% vs 6.7% ADCmedian) and for mid (n = 14) vs apical (n = 9) or lower zone (n = 13) lesions (13.9%, 2.7%, 3.8% respectively ADCmean; 14.2%, 2.8%, 4.7% respectively ADCmedian). Free-breathing DW-MRI of whole lung achieves good intra- and inter-observer repeatability of ADC measurements in malignant lung tumours. • Diffusion-weighted MRI of the lung can be satisfactorily acquired during free-breathing • DW-MRI demonstrates high contrast between primary and metastatic lesions and normal lung • Apparent diffusion coefficient (ADC) measurements in lung tumours are repeatable and reliable • ADC offers potential in assessing response in lung metastases in clinical trials.

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.

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.

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.

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.

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

PubMed

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

2016-03-01

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

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

PubMed

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

2017-01-01

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

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

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.

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

NASA Technical Reports Server (NTRS)

Luna, Michael E.; Collins, Steven M.

2011-01-01

On November 4, 2010 the former "Deep Impact" spacecraft, renamed "EPOXI" for its extended mission, flew within 700km of comet 103P/Hartley 2. In July 2005, the spacecraft had previously imaged a probe impact of comet Tempel 1. The EPOXI flyby was the fifth close encounter of a spacecraft with a comet nucleus and marked the first time in history that two comet nuclei were imaged at close range with the same suite of onboard science instruments. This challenging objective made the function of the attitude determination and control subsystem (ADCS) critical to the successful execution of the EPOXI flyby.As part of the spacecraft flyby preparations, the ADCS operations team had to perform meticulous sequence reviews, implement complex spacecraft engineering and science activities and perform numerous onboard calibrations. ADCS contributions included design and execution of 10 trajectory correction maneuvers, the science calibration of the two telescopic instruments, an in-flight demonstration of high-rate turns between Earth and comet point, and an ongoing assessment of reaction wheel health. The ADCS team was also responsible for command sequences that included updates to the onboard ephemeris and sun sensor coefficients and implementation of reaction wheel assembly (RWA) de-saturations.

Differential effects of predosing on tumor and tissue uptake of an 111In-labeled anti-TENB2 antibody-drug conjugate.

PubMed

Boswell, C Andrew; Mundo, Eduardo E; Zhang, Crystal; Stainton, Shannon L; Yu, Shang-Fan; Lacap, Jennifer A; Mao, Weiguang; Kozak, Katherine R; Fourie, Aimee; Polakis, Paul; Khawli, Leslie A; Lin, Kedan

2012-09-01

TENB2, also known as tomoregulin or transmembrane protein with epidermal growth factor-like and 2 follistatin-like domains, is a transmembrane proteoglycan overexpressed in human prostate tumors. This protein is a promising target for antimitotic monomethyl auristatin E (MMAE)-based antibody-drug conjugate (ADC) therapy. Nonlinear pharmacokinetics in normal mice suggested that antigen expression in normal tissues may contribute to targeted mediated disposition. We evaluated a predosing strategy with unconjugated antibody to block ADC uptake in target-expressing tissues in a mouse model while striving to preserve tumor uptake and efficacy. Unconjugated, unlabeled antibody was preadministered to mice bearing the TENB2-expressing human prostate explant model, LuCaP 77, followed by a single administration of (111)In-labeled anti-TENB2-MMAE for biodistribution and SPECT/CT studies. A tumor-growth-inhibition study was conducted to determine the pharmacodynamic consequences of predosing. Preadministration of anti-TENB2 at 1 mg/kg significantly increased blood exposure of the radiolabeled ADC and reduced intestinal, hepatic, and splenic uptake while not affecting tumor accretion. Similar tumor-to-heart ratios were measured by SPECT/CT at 24 h with and without the predose. Consistent with this, the preadministration of 0.75 mg/kg did not interfere with efficacy in a tumor-growth study dosed at 0.75 mg or 2.5 mg of ADC per kilogram. Overall, the potential to mask peripheral, nontumor antigen uptake while preserving tumor uptake and efficacy could ameliorate toxicity and may significantly affect future dosing strategies for ADCs.

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.

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.

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.

Diffusion-weighted imaging of mucinous carcinoma of the breast: evaluation of apparent diffusion coefficient and signal intensity in correlation with histologic findings.

PubMed

Woodhams, Reiko; Kakita, Satoko; Hata, Hirofumi; Iwabuchi, Keiichi; Umeoka, Shigeaki; Mountford, Carolyn E; Hatabu, Hiroto

2009-07-01

The purposes of this study were to compare the apparent diffusion coefficient (ADC) of mucinous carcinoma of the breast with that of other breast tumors and to analyze correlations between signal intensity on diffusion-weighted images and the histologic features of mucinous carcinoma. Two hundred seventy-six patients with 277 lesions, including 15 mucinous carcinomas (13 pure type, two mixed type), 204 other malignant tumors, and 58 benign lesions, were examined with 1.5-T MRI at b values of 0 and 1,500 s/mm(2). The correlations between cellularity and ADC, homogeneity of signal intensity on diffusion-weighted images, and histopathologic findings were analyzed. The difference was statistically significant (p < 0.05). The mean ADC of mucinous carcinoma (1.8 +/- 0.4 x 10(-3) mm(2)/s) was statistically higher than that of benign lesions (1.3+/- 0.3 x 10(-3) mm(2)/s) and other malignant tumors (0.9 +/- 0.2 x 10(-3) mm(2)/s) (p < 0.001). The ADC of pure type mucinous carcinoma (1.8 +/- 0.3 x 10(-3) mm(2)/s) was higher than that of mixed type mucinous carcinoma (1.2 +/- 0.2 x 10(-3) mm(2)/s) (p < 0.001) and other histologic types (p > 0.05). The correlation between mean cellularity and the ADC of mucinous carcinoma was significant (rho(s) = -0.754; p = 0.001). The homogeneity of signal intensity on diffusion-weighted images correlated with the homogeneity of histologic structures of mucinous carcinoma (p < 0.001; kappa = 0.826). Mucinous carcinoma can be clearly differentiated from other breast tumors on the basis of ADC. The low signal intensity of mucinous carcinoma on diffusion-weighted images appears to reflect the presence of mucin and low cellularity. High signal intensity on diffusion-weighted images may reflect the presence of fibrovascular bundles, increased cell density, or a combination of these features.

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

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

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

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.

[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.

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

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.

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.

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.

The Usefulness of Readout-Segmented Echo-Planar Imaging (RESOLVE) for Bio-phantom Imaging Using 3-Tesla Clinical MRI.

PubMed

Yoshimura, Yuuki; Kuroda, Masahiro; Sugiantoc, Irfan; Bamgbosec, Babatunde O; Miyahara, Kanae; Ohmura, Yuichi; Kurozumi, Akira; Matsushita, Toshi; Ohno, Seiichiro; Kanazawa, Susumu; Asaumi, Junichi

2018-02-01

Readout-segmented echo-planar imaging (RESOLVE) is a multi-shot echo-planar imaging (EPI) modality with k-space segmented in the readout direction. We investigated whether RESOLVE decreases the distortion and artifact in the phase direction and increases the signal-to-noise ratio (SNR) in phantoms image taken with 3-tesla (3T) MRI versus conventional EPI. We used a physiological saline phantom and subtraction mapping and observed that RESOLVE's SNR was higher than EPI's. Using RESOLVE, the combination of a special-purpose coil and a large-loop coil had a higher SNR compared to using only a head/neck coil. RESOLVE's image distortioas less than EPI's. We used a 120 mM polyethylene glycol phantom to examine the phase direction artifact.vThe range where the artifact appeared in the apparent diffusion coefficient (ADC) image was shorter with RESOLVE compared to EPI. We used RESOLVE to take images of a Jurkat cell bio-phantom: the cell-region ADC was 856×10-6mm2/sec and the surrounding physiological saline-region ADC was 2,951×10-6mm2/sec. The combination of RESOLVE and the 3T clinical MRI device reduced image distortion and improved SNR and the identification of accurate ADC values due to the phase direction artifact reduction. This combination is useful for obtaining accurate ADC values of bio-phantoms.

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.

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.

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.

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.

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

PubMed

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

2017-10-01

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

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

PubMed

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

2015-01-01

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

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

PubMed

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

2018-05-14

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

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.

A Fast Multiple Sampling Method for Low-Noise CMOS Image Sensors With Column-Parallel 12-bit SAR ADCs.

PubMed

Kim, Min-Kyu; Hong, Seong-Kwan; Kwon, Oh-Kyong

2015-12-26

This paper presents a fast multiple sampling method for low-noise CMOS image sensor (CIS) applications with column-parallel successive approximation register analog-to-digital converters (SAR ADCs). The 12-bit SAR ADC using the proposed multiple sampling method decreases the A/D conversion time by repeatedly converting a pixel output to 4-bit after the first 12-bit A/D conversion, reducing noise of the CIS by one over the square root of the number of samplings. The area of the 12-bit SAR ADC is reduced by using a 10-bit capacitor digital-to-analog converter (DAC) with four scaled reference voltages. In addition, a simple up/down counter-based digital processing logic is proposed to perform complex calculations for multiple sampling and digital correlated double sampling. To verify the proposed multiple sampling method, a 256 × 128 pixel array CIS with 12-bit SAR ADCs was fabricated using 0.18 μm CMOS process. The measurement results shows that the proposed multiple sampling method reduces each A/D conversion time from 1.2 μs to 0.45 μs and random noise from 848.3 μV to 270.4 μV, achieving a dynamic range of 68.1 dB and an SNR of 39.2 dB.

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.

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.

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

PubMed

Fekete, Szabolcs; Molnár, Imre; Guillarme, Davy

2017-04-15

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

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

PubMed

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

2013-06-01

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

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.

Virologic and Immunologic Outcomes in HIV-Infected Patients with Cancer.

PubMed

Riedel, David J; Stafford, Kristen A; Vadlamani, Aparna; Redfield, Robert R

2017-05-01

Achievement and maintenance of virologic suppression after cancer diagnosis have been associated with improved outcomes in HIV-infected patients, but few studies have analyzed the virologic and immunologic outcomes after a cancer diagnosis. All HIV-infected patients with a diagnosis of cancer between 2000 and 2011 in an urban clinic population in Baltimore, MD, were included for review. HIV-related outcomes (HIV-1 RNA viral load and CD4 cell count) were abstracted and compared for patients with non-AIDS-defining cancers (NADCs) and AIDS-defining cancers (ADCs). Four hundred twelve patients with baseline CD4 or HIV-1 RNA viral load data were analyzed. There were 122 (30%) diagnoses of ADCs and 290 (70%) NADCs. Patients with NADCs had a higher median age (54 years vs. 43 years, p < .0001) and a higher frequency of hepatitis C coinfection (52% vs. 36%, p = .002). The median baseline CD4 was lower for patients with ADCs (137 cells/mm 3 vs. 314 cells/mm 3 ) and patients with NADCs were more likely to be suppressed at cancer diagnosis (59% vs. 25%) (both p < .0001). The median CD4 for patients with NADCs was significantly higher than patients with ADCs at 6 and 12 months after diagnosis and higher at 18 and 24 months, but not significantly. Patients with an NADC had 2.19 times (95% CI 1.04-4.62) the adjusted odds of being suppressed at 12 months and 2.17 times the odds (95% CI 0.92-5.16) at 24 months compared to patients with an ADC diagnosis. For patients diagnosed with ADCs and NADCs in this urban clinic setting, both virologic suppression and immunologic recovery improved over time. Patients with NADCs had the highest odds of virologic suppression in the 2 years following cancer diagnosis.

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.

Aspartate Decarboxylase is Required for a Normal Pupa Pigmentation Pattern in the Silkworm, Bombyx mori.

PubMed

Dai, Fangyin; Qiao, Liang; Cao, Cun; Liu, Xiaofan; Tong, Xiaoling; He, Songzhen; Hu, Hai; Zhang, Li; Wu, Songyuan; Tan, Duan; Xiang, Zhonghuai; Lu, Cheng

2015-06-16

The pigmentation pattern of Lepidoptera varies greatly in different development stages. To date, the effects of key genes in the melanin metabolism pathway on larval and adult body color are distinct, yet the effects on pupal pigmentation remains unclear. In the silkworm, Bombyx mori, the black pupa (bp) mutant is only specifically melanized at the pupal stage. Using positional cloning, we found that a mutation in the Aspartate decarboxylase gene (BmADC) is causative in the bp mutant. In the bp mutant, a SINE-like transposon with a length of 493 bp was detected ~2.2 kb upstream of the transcriptional start site of BmADC. This insertion causes a sharp reduction in BmADC transcript levels in bp mutants, leading to deficiency of β-alanine and N-β-alanyl dopamine (NBAD), but accumulation of dopamine. Following injection of β-alanine into bp mutants, the color pattern was reverted that of the wild-type silkworms. Additionally, melanic pupae resulting from knock-down of BmADC in the wild-type strain were obtained. These findings show that BmADC plays a crucial role in melanin metabolism and in the pigmentation pattern of the silkworm pupal stage. Finally, this study contributes to a better understanding of pupa pigmentation patterns in Lepidoptera.

Aspartate Decarboxylase is Required for a Normal Pupa Pigmentation Pattern in the Silkworm, Bombyx mori

PubMed Central

Dai, Fangyin; Qiao, Liang; Cao, Cun; Liu, Xiaofan; Tong, Xiaoling; He, Songzhen; Hu, Hai; Zhang, Li; Wu, Songyuan; Tan, Duan; Xiang, Zhonghuai; Lu, Cheng

2015-01-01

The pigmentation pattern of Lepidoptera varies greatly in different development stages. To date, the effects of key genes in the melanin metabolism pathway on larval and adult body color are distinct, yet the effects on pupal pigmentation remains unclear. In the silkworm, Bombyx mori, the black pupa (bp) mutant is only specifically melanized at the pupal stage. Using positional cloning, we found that a mutation in the Aspartate decarboxylase gene (BmADC) is causative in the bp mutant. In the bp mutant, a SINE-like transposon with a length of 493 bp was detected ~2.2 kb upstream of the transcriptional start site of BmADC. This insertion causes a sharp reduction in BmADC transcript levels in bp mutants, leading to deficiency of β-alanine and N-β-alanyl dopamine (NBAD), but accumulation of dopamine. Following injection of β-alanine into bp mutants, the color pattern was reverted that of the wild-type silkworms. Additionally, melanic pupae resulting from knock-down of BmADC in the wild-type strain were obtained. These findings show that BmADC plays a crucial role in melanin metabolism and in the pigmentation pattern of the silkworm pupal stage. Finally, this study contributes to a better understanding of pupa pigmentation patterns in Lepidoptera. PMID:26077025

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

PubMed

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

2016-03-01

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

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.

Water solvent effects using continuum and discrete models: The nitromethane molecule, CH3NO2.

PubMed

Modesto-Costa, Lucas; Uhl, Elmar; Borges, Itamar

2015-11-15

The first three valence transitions of the two nitromethane conformers (CH3NO2) are two dark n → π* transitions and a very intense π → π* transition. In this work, these transitions in gas-phase and solvated in water of both conformers were investigated theoretically. The polarizable continuum model (PCM), two conductor-like screening (COSMO) models, and the discrete sequential quantum mechanics/molecular mechanics (S-QM/MM) method were used to describe the solvation effect on the electronic spectra. Time dependent density functional theory (TDDFT), configuration interaction including all single substitutions and perturbed double excitations (CIS(D)), the symmetry-adapted-cluster CI (SAC-CI), the multistate complete active space second order perturbation theory (CASPT2), and the algebraic-diagrammatic construction (ADC(2)) electronic structure methods were used. Gas-phase CASPT2, SAC-CI, and ADC(2) results are in very good agreement with published experimental and theoretical spectra. Among the continuum models, PCM combined either with CASPT2, SAC-CI, or B3LYP provided good agreement with available experimental data. COSMO combined with ADC(2) described the overall trends of the transition energy shifts. The effect of increasing the number of explicit water molecules in the S-QM/MM approach was discussed and the formation of hydrogen bonds was clearly established. By including explicitly 24 water molecules corresponding to the complete first solvation shell in the S-QM/MM approach, the ADC(2) method gives more accurate results as compared to the TDDFT approach and with similar computational demands. The ADC(2) with S-QM/MM model is, therefore, the best compromise for accurate solvent calculations in a polar environment. © 2015 Wiley Periodicals, Inc.

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

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

PubMed Central

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

2011-01-01

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

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

PubMed

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

2012-01-01

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

The Variable Warm Absorber in Circinus X-1

NASA Astrophysics Data System (ADS)

Schulz, N. S.; Kallman, T. E.; Galloway, D. K.; Brandt, W. N.

2008-01-01

We observed Circinus X-1 twice during a newly reached low-flux phase near zero orbital phase using the High-Energy Transmission Grating Spectrometer (HETGS) onboard Chandra. In both observations the source did not show the P Cygni lines we observed during the high-flux phases of the source in 2000 and 2001. During the prezero phase the source did not exhibit significant variability but did exhibit an emission-line spectrum rich in H- and He-like lines from high-Z elements such as Si, S, Ar, and Ca. The light curve in the postdip observation showed quiescent and flaring episodes. Only in these flaring episodes was the source luminosity significantly higher than observed during the prezero phase. We analyzed all high-resolution X-ray spectra by fitting photoionization and absorption models from the most recent version of the XSTAR code. The prezero-phase spectrum could be fully modeled with a very hot photoionized plasma with an ionization parameter of log ξ = 3.0, down from log ξ = 4.0 in the high-flux state. The ionization balances we measure from the spectra during the postzero-phase episodes are significantly different. Both episodes feature absorbers with variable high columns, ionization parameters, and luminosity. While cold absorption remains at levels quite similar to that observed in previous years, the new observations show unprecedented levels of variable warm absorption. The line emissivities also indicate that the observed low source luminosity is inconsistent with a static hot accretion disk corona (ADC), an effect that seems common to other near-edge-on ADC sources as well. We conclude that unless there exists some means of coronal heating other than X-rays, the true source luminosity is likely much higher, and we observe obscuration in analogy to the extragalactic Seyfert 2 sources. We discuss possible consequences and relate cold, lukewarm, warm, and hot absorbers to dynamic accretion scenarios.

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.

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

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

PubMed

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

2014-01-01

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

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.

Ocular Adverse Events Associated with Antibody–Drug Conjugates in Human Clinical Trials

PubMed Central

Miller, Paul E.; Mannis, Mark J.

2015-01-01

Abstract This article reviews ocular adverse events (AEs) reported in association with administration of antibody–drug conjugates (ADCs) in human clinical trials. References reporting ocular toxicity or AEs associated with ADCs were collected using online publication searches. Articles, abstracts, or citations were included if they cited ocular toxicities or vision-impairing AEs with a confirmed or suspected association with ADC administration. Twenty-two references were found citing ocular or vision-impairing AEs in association with ADC administration. All references reported use of ADCs in human clinical trials for treatment of various malignancies. The molecular target and cytotoxic agent varied depending on the ADC used. Ocular AEs affected a diversity of ocular tissues. The most commonly reported AEs involved the ocular surface and included blurred vision, dry eye, and corneal abnormalities (including microcystic corneal disease). Most ocular AEs were not severe (≤ grade 2) or dose limiting. Clinical outcomes were not consistently reported, but when specified, most AEs improved or resolved with cessation of treatment or with ameliorative therapy. A diverse range of ocular AEs are reported in association with administration of ADCs for the treatment of cancer. The toxicologic mechanism(s) and pathogenesis of such events are not well understood, but most are mild in severity and reversible. Drug development and medical professionals should be aware of the clinical features of these events to facilitate early recognition and intervention in the assessment of preclinical development programs and in human clinical trials. PMID:26539624

An integrated approach to identify normal tissue expression of targets for antibody-drug conjugates: case study of TENB2

PubMed Central

Boswell, C Andrew; Mundo, Eduardo E; Firestein, Ron; Zhang, Crystal; Mao, Weiguang; Gill, Herman; Young, Cynthia; Ljumanovic, Nina; Stainton, Shannon; Ulufatu, Sheila; Fourie, Aimee; Kozak, Katherine R; Fuji, Reina; Polakis, Paul; Khawli, Leslie A; Lin, Kedan

2013-01-01

Background and Purpose The success of antibody-drug conjugates (ADCs) depends on the therapeutic window rendered by the differential expression between normal and pathological tissues. The ability to identify and visualize target expression in normal tissues could reveal causes for target-mediated clearance observed in pharmacokinetic characterization. TENB2 is a prostate cancer target associated with the progression of poorly differentiated and androgen-independent tumour types, and ADCs specific for TENB2 are candidate therapeutics. The objective of this study was to locate antigen expression of TENB2 in normal tissues, thereby elucidating the underlying causes of target-mediated clearance. Experimental Approach A series of pharmacokinetics, tissue distribution and mass balance studies were conducted in mice using a radiolabelled anti-TENB2 ADC. These data were complemented by non-invasive single photon emission computed tomography – X-ray computed tomography imaging and immunohistochemistry. Key Results The intestines were identified as a saturable and specific antigen sink that contributes, at least in part, to the rapid target-mediated clearance of the anti-TENB2 antibody and its drug conjugate in rodents. As a proof of concept, we also demonstrated the selective disposition of the ADC in a tumoural environment in vivo using the LuCaP 77 transplant mouse model. High tumour uptake was observed despite the presence of the antigen sink, and antigen specificity was confirmed by antigen blockade. Conclusions and Implications Our findings provide the anatomical location and biological interpretation of target-mediated clearance of anti-TENB2 antibodies and corresponding drug conjugates. Further investigations may be beneficial in addressing the relative contributions to ADC disposition from antigen expression in both normal and pathological tissues. PMID:22889168

An integrated approach to identify normal tissue expression of targets for antibody-drug conjugates: case study of TENB2.

PubMed

Boswell, C Andrew; Mundo, Eduardo E; Firestein, Ron; Zhang, Crystal; Mao, Weiguang; Gill, Herman; Young, Cynthia; Ljumanovic, Nina; Stainton, Shannon; Ulufatu, Sheila; Fourie, Aimee; Kozak, Katherine R; Fuji, Reina; Polakis, Paul; Khawli, Leslie A; Lin, Kedan

2013-01-01

The success of antibody-drug conjugates (ADCs) depends on the therapeutic window rendered by the differential expression between normal and pathological tissues. The ability to identify and visualize target expression in normal tissues could reveal causes for target-mediated clearance observed in pharmacokinetic characterization. TENB2 is a prostate cancer target associated with the progression of poorly differentiated and androgen-independent tumour types, and ADCs specific for TENB2 are candidate therapeutics. The objective of this study was to locate antigen expression of TENB2 in normal tissues, thereby elucidating the underlying causes of target-mediated clearance. A series of pharmacokinetics, tissue distribution and mass balance studies were conducted in mice using a radiolabelled anti-TENB2 ADC. These data were complemented by non-invasive single photon emission computed tomography - X-ray computed tomography imaging and immunohistochemistry. The intestines were identified as a saturable and specific antigen sink that contributes, at least in part, to the rapid target-mediated clearance of the anti-TENB2 antibody and its drug conjugate in rodents. As a proof of concept, we also demonstrated the selective disposition of the ADC in a tumoural environment in vivo using the LuCaP 77 transplant mouse model. High tumour uptake was observed despite the presence of the antigen sink, and antigen specificity was confirmed by antigen blockade. Our findings provide the anatomical location and biological interpretation of target-mediated clearance of anti-TENB2 antibodies and corresponding drug conjugates. Further investigations may be beneficial in addressing the relative contributions to ADC disposition from antigen expression in both normal and pathological tissues. © 2012 Genentech, Inc.. British Journal of Pharmacology © 2012 The British Pharmacological Society.

A monte carlo study of restricted diffusion: Implications for diffusion MRI of prostate cancer.

PubMed

Gilani, Nima; Malcolm, Paul; Johnson, Glyn

2017-04-01

Diffusion MRI is used frequently to assess prostate cancer. The prostate consists of cellular tissue surrounding fluid filled ducts. Here, the diffusion properties of the ductal fluid alone were studied. Monte Carlo simulations were used to investigate ductal residence times to determine whether ducts can be regarded as forming a separate compartment and whether ductal radius could determine the Apparent Diffusion Coefficient (ADC) of the ductal fluid. Random walks were simulated in cavities. Average residence times were estimated for permeable cavities. Signal reductions resulting from application of a Stejskal-Tanner pulse sequence were calculated in impermeable cavities. Simulations were repeated for cavities of different radii and different diffusion times. Residence times are at least comparable with diffusion times even in relatively high grade tumors. ADCs asymptotically approach theoretical limiting values. At large radii and short diffusion times, ADCs are similar to free diffusion. At small radii and long diffusion times, ADCs are reduced toward zero, and kurtosis approaches a value of -1.2. Restricted diffusion in cavities of similar sizes to prostate ducts may reduce ductal ADCs. This may contribute to reductions in total ADC seen in prostate cancer. Magn Reson Med 77:1671-1677, 2017. © 2016 International Society for Magnetic Resonance in Medicine. © 2016 International Society for Magnetic Resonance in Medicine.

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.

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.

Lipid peroxidation and antioxidant status in colorectal cancer

PubMed Central

Skrzydlewska, Elzbieta; Sulkowski, Stanislaw; Koda, Mariusz; Zalewski, Bogdan; Kanczuga-Koda, Luiza; Sulkowska, Mariola

2005-01-01

AIM: Reactive oxygen species (ROS) can induce carcinogenesis via DNA injury. Both enzymatic and non-enzymatic parameters participate in cell protection against harmful influence of oxidative stress. The aim of the present study was to assess the levels of final lipid peroxidation products like malondialdehyde (MDA) and 4-hydroxy-2-nonenal (4-HNE) in primary colorectal cancer. Moreover, we analysed the activity of main antioxidative enzymes, superoxide dismutase (Cu, Zn-SOD), catalase (CAT), glutathione peroxidase (GSH-Px) and glutathione reductase (GSSRG-R) and the level of non-enzymatic antioxidants (glutathione, vitamins C and E). METHODS: Investigations were conducted in 81 primary colorectal cancers. As a control, the same amount of sample was collected from macroscopically unchanged colon regions of the most distant location to the cancer. Homogenisation of specimens provided 10% homogenates for our evaluations. Activity of antioxidant enzymes and level of glutathione were determined by spectrophotometry. HPLC revealed levels of vitamins C and E and served as a method to detect terminal products of lipid peroxidation in colorectal cancer. RESULTS: Our studies demonstrated a statistically significant increase in the level of lipid peroxidation products (MDA-Adc.muc.-2.65±0.48 nmol/g, Adc.G3-2.15±0.44 nmol/g, clinical IV stage 4.04±0.47 nmol/g, P<0.001 and 4-HNE-Adc.muc. -0.44±0.07 nmol/g, Adc.G3-0.44±0.10 nmol/g, clinical IV stage 0.52±0.11 nmol/g, P<0.001) as well as increase of Cu,Zn-SOD (Adc.muc.-363±72 U/g, Adc.G3-318±48 U/g, clinical IV stage 421±58 U/g, P<0.001), GSH-Px (Adc.muc. -2143±623 U/g, Adc.G3-2005±591 U/g, clinical IV stage 2467±368 U/g, P<0.001) and GSSG-R (Adc.muc.-880±194 U/g, Adc.G3-795±228 U/g, clinical IV stage 951±243 U/g, P<0.001) in primary tumour comparison with normal colon (MDA-1.39±0.15 nmol/g, HNE-0.29±0.03 nmol/g, Cu, Zn-SOD-117±25 U/g, GSH-Px-1723±189 U/g, GSSG-R-625±112 U/g) especially in mucinous and G3-grade adenocarcinomas as well as clinical IV stage of colorectal cancer. We also observed a decrease of CAT activity (Adc.muc. -40±14 U/g, clinical IV stage 33±18 U/g vs 84±17 U/g, P<0.001) as well as a decreased level of reduced glutathione (clinical IV stage 150±48 nmol/g vs 167±15 nmol/g, P<0.05) and vitamins C and E (vit. C-clinical IV stage 325±92 nmol/g vs 513±64 nmol/g, P<0.001; vit. E-clinical IV stage 13.3±10.3 nmol/g vs 37.5±5.2 nmol/g). CONCLUSION: Colorectal carcinogenesis is associated with serious oxidative stress and confirms that gradual advancement of oxidative-antioxidative disorders is followed by progression of colorectal cancer. PMID:15637754

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.

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.

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.

Differences in Brain Morphological Findings between Narcolepsy with and without Cataplexy

PubMed Central

Nakamura, Masaki; Nishida, Shingo; Hayashida, Kenichi; Ueki, Yoichiro; Dauvilliers, Yves; Inoue, Yuichi

2013-01-01

Objective Maps of fractional anisotropy (FA) and apparent diffusion coefficient (ADC) obtained by diffusion tensor imaging (DTI) can detect microscopic axonal changes by estimating the diffusivity of water molecules using magnetic resonance imaging (MRI). We applied an MRI voxel-based statistical approach to FA and ADC maps to evaluate microstructural abnormalities in the brain in narcolepsy and to investigate differences between patients having narcolepsy with and without cataplexy. Methods Twelve patients with drug-naive narcolepsy with cataplexy (NA/CA), 12 with drug-naive narcolepsy without cataplexy (NA w/o CA) and 12 age-matched healthy normal controls (NC) were enrolled. FA and ADC maps for these 3 groups were statistically compared by using voxel-based one-way ANOVA. In addition, we investigated the correlation between FA and ADC values and clinical variables in the patient groups. Results Compared to the NC group, the NA/CA group showed higher ADC values in the left inferior frontal gyrus and left amygdala, and a lower ADC value in the left postcentral gyrus. The ADC value in the right inferior frontal gyrus and FA value in the right precuneus were higher for NA/CA group than for the NA w/o CA group. However, no significant differences were observed in FA and ADC values between the NA w/o CA and NC groups in any of the areas investigated. In addition, no correlation was found between the clinical variables and ADC and FA values of any brain areas in these patient groups. Conclusions Several microstructural changes were noted in the inferior frontal gyrus and amygdala in the NA/CA but not in the NA w/o CA group. These findings suggest that these 2 narcolepsy conditions have different pathological mechanisms: narcolepsy without cataplexy form appears to be a potentially broader condition without any significant brain imaging differences from normal controls. PMID:24312261

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.

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

A high SFDR 6-bit 20-MS/s SAR ADC based on time-domain comparator

NASA Astrophysics Data System (ADS)

Xue, Han; Hua, Fan; Qi, Wei; Huazhong, Yang

2013-08-01

This paper presents a 6-bit 20-MS/s high spurious-free dynamic range (SFDR) and low power successive approximation register analog to digital converter (SAR ADC) for the radio-frequency (RF) transceiver front-end, especially for wireless sensor network (WSN) applications. This ADC adopts the modified common-centroid symmetry layout and the successive approximation register reset circuit to improve the linearity and dynamic range. Prototyped in a 0.18-μm 1P6M CMOS technology, the ADC performs a peak SFDR of 55.32 dB and effective number of bits (ENOB) of 5.1 bit for 10 MS/s. At the sample rate of 20 MS/s and the Nyquist input frequency, the 47.39-dB SFDR and 4.6-ENOB are achieved. The differential nonlinearity (DNL) is less than 0.83 LSB and the integral nonlinearity (INL) is less than 0.82 LSB. The experimental results indicate that this SAR ADC consumes a total of 522 μW power and occupies 0.98 mm2.

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.

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.

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.

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.

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

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

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

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

Development of New ADC Technology with Topoisomerase I Inhibitor.

PubMed

Agatsuma, Toshinori

2017-01-01

Antibody-drug conjugates (ADCs) selectively deliver large amounts of antitumor drugs to tumor tissue and show significant antitumor effects with a wide therapeutic window. We developed a new linker-drug technology platform with an exatecan derivative, which is a highly potent topoisomerase I inhibitor. The major advantages of the technology are: 1) high and homogeneous drug-to-antibody ratio (DAR) availability; 2) potent antitumor activity in conjunction with bystander killing; 3) few safety concerns because of the stable linker limiting release of free drug; and 4) a wide application to therapeutic antibodies. Using this linker-drug technology, we generated an anti-HER2 ADC, namely DS-8201a. DS-8201a, in which almost all eight cysteine residues of the antibody are bound to drug, was effective against trastuzumab DM1 (T-DM1)-insensitive patient-derived xenograft (PDX) models with high HER2 expression and also demonstrated antitumor efficacy against several breast cancer PDX models with low HER2 expression. DS-8201a was well tolerated in rats and monkeys following repeated administration. These results suggest that DS-8201a may be efficacious in a broader population of HER2-positive cancer patients and also confirm the importance of this new class of novel topoisomerase I inhibitor-based ADC technology.

[Correlations between apparent diffusion coefficient in diffusion?weighted magnetic resonance imaging and molecular subtypes of invasive breast cancer masses].

PubMed

Shang, Liu-Tong; Yang, Jia-Fei; Lu, Jing; Wang, Ting-Ting; Zhou, Ying; Xing, Xin-Bo; Wang, Xin-Kun; Yang, Shu-Hui; Hu, Ming-Yan

2017-10-20

To study the correlation of apparent diffusion coefficient (ADC) measured by diffusion-weighted magnetic resonance imaging (MRI) with the molecular subtypes and biological prognostic factors of invasive breast cancer masses. Breast MRI data (including dynamic enhanced and diffusion-weighted imaging) were collected from 64 patients with pathologically confirmed invasive breast cancer masses (a total of 69 lesions). The mean ADC values of the lesions were calculated and their correlations were analyzed with the 5 molecular subtypes of invasive breast cancer and the biological prognostic factors including estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor 2 (HER2), and Ki-67 index. The ADC values did not differ significantly among the 5 molecular subtypes of invasive breast cancer masses (P>0.05) or among lesions with different ER, PR, or HER2 status (P>0.05). The mean ADC values were significantly higher in Ki-67-positive lesions than in the negative lesions (P=0.023 and negatively correlated with the expressions of Ki-67 (r=-0.249). ADC value can not be used to identify the molecular subtypes of invasive breast cancer masses or to evaluate the biological prognosis of the lesions, but its correlation with Ki-67 expression may help in prognostic evaluation and guiding clinical therapy of the tumors.

Successive approximation-like 4-bit full-optical analog-to-digital converter based on Kerr-like nonlinear photonic crystal ring resonators

NASA Astrophysics Data System (ADS)

Tavousi, Alireza; Mansouri-Birjandi, Mohammad Ali; Saffari, Mehdi

2016-09-01

Implementing of photonic sampling and quantizing analog-to-digital converters (ADCs) enable us to extract a single binary word from optical signals without need for extra electronic assisting parts. This would enormously increase the sampling and quantizing time as well as decreasing the consumed power. To this end, based on the concept of successive approximation method, a 4-bit full-optical ADC that operates using the intensity-dependent Kerr-like nonlinearity in a two dimensional photonic crystal (2DPhC) platform is proposed. The Silicon (Si) nanocrystal is chosen because of the suitable nonlinear material characteristic. An optical limiter is used for the clamping and quantization of each successive levels that represent the ADC bits. In the proposal, an energy efficient optical ADC circuit is implemented by controlling the system parameters such as ring-to-waveguide coupling coefficients, the ring's nonlinear refractive index, and the ring's length. The performance of the ADC structure is verified by the simulation using finite difference time domain (FDTD) method.

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

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.

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

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.

Diffusion-weighted magnetic resonance imaging reveals the effects of different cooling temperatures on the diffusion of water molecules and perfusion within human skeletal muscle.

PubMed

Yanagisawa, O; Fukubayashi, T

2010-11-01

To evaluate the effect of local cooling on the diffusion of water molecules and perfusion within muscle at different cooling temperatures. Magnetic resonance diffusion-weighted (DW) images of the leg (seven males) were obtained before and after 30 min cooling (0, 10, and 20°C), and after a 30 min recovery period. Two types of apparent diffusion coefficient (ADC; ADC1, reflecting both water diffusion and perfusion within muscle, and ADC2, approximating the true water diffusion coefficient) of the ankle dorsiflexors were calculated from DW images. T2-weighted images were also obtained to calculate T2 values of the ankle dorsiflexors. The skin temperature was measured before, during, and after cooling. Both ADC values significantly decreased after cooling under all cooling conditions; the rate of decrease depended on the cooling temperature used (ADC1: -36% at 0°C, -27.8% at 10°C, and -22.6% at 20°C; ADC2: -26% at 0°C, -21.1% at 10°C, and -14.6% at 20°C). These significant decreases were maintained during the recovery period. Conversely, the T2 value showed no significant changes. Under all cooling conditions, skin temperature significantly decreased during cooling; the rate of decrease depended on the cooling temperature used (-74.8% at 0°C, -51.1% at 10°C, and -26.8% at 20°C). Decreased skin temperatures were not restored to pre-cooling values during the recovery period under any cooling conditions. Local cooling decreased the water diffusion and perfusion within muscle with decreased skin temperature; the rates of decrease depended on the cooling temperature used. These decreases were maintained for 30 min after cooling. Copyright © 2010 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Improved Tumor Penetration and Single-Cell Targeting of Antibody-Drug Conjugates Increases Anticancer Efficacy and Host Survival.

PubMed

Cilliers, Cornelius; Menezes, Bruna; Nessler, Ian; Linderman, Jennifer; Thurber, Greg M

2018-02-01

Current antibody-drug conjugates (ADC) have made advances in engineering the antibody, linker, conjugation site, small-molecule payload, and drug-to-antibody ratio (DAR). However, the relationship between heterogeneous intratumoral distribution and efficacy of ADCs is poorly understood. Here, we compared trastuzumab and ado-trastuzumab emtansine (T-DM1) to study the impact of ADC tumor distribution on efficacy. In a mouse xenograft model insensitive to trastuzumab, coadministration of trastuzumab with a fixed dose of T-DM1 at 3:1 and 8:1 ratios dramatically improved ADC tumor penetration and resulted in twice the improvement in median survival compared with T-DM1 alone. In this setting, the effective DAR was lowered, decreasing the amount of payload delivered to each targeted cell but increasing the number of cells that received payload. This result is counterintuitive because trastuzumab acts as an antagonist in vitro and has no single-agent efficacy in vivo , yet improves the effectiveness of T-DM1 in vivo Novel dual-channel fluorescence ratios quantified single-cell ADC uptake and metabolism and confirmed that the in vivo cellular dose of T-DM1 alone exceeded the minimum required for efficacy in this model. In addition, this technique characterized cellular pharmacokinetics with heterogeneous delivery after 1 day, degradation and payload release by 2 days, and in vitro cell killing and in vivo tumor shrinkage 2 to 3 days later. This work demonstrates that the intratumoral distribution of ADC, independent of payload dose or plasma clearance, plays a major role in ADC efficacy. Significance: This study shows how lowering the drug-to-antibody ratio during treatment can improve the intratumoral distribution of a antibody-drug conjugate, with implications for improving the efficacy of this class of cancer drugs. Cancer Res; 78(3); 758-68. ©2017 AACR . ©2017 American Association for Cancer Research.

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.

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.

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

PubMed

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

2015-08-01

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

T2-weighted MRI-derived textural features reflect prostate cancer aggressiveness: preliminary results.

PubMed

Nketiah, Gabriel; Elschot, Mattijs; Kim, Eugene; Teruel, Jose R; Scheenen, Tom W; Bathen, Tone F; Selnæs, Kirsten M

2017-07-01

To evaluate the diagnostic relevance of T2-weighted (T2W) MRI-derived textural features relative to quantitative physiological parameters derived from diffusion-weighted (DW) and dynamic contrast-enhanced (DCE) MRI in Gleason score (GS) 3+4 and 4+3 prostate cancers. 3T multiparametric-MRI was performed on 23 prostate cancer patients prior to prostatectomy. Textural features [angular second moment (ASM), contrast, correlation, entropy], apparent diffusion coefficient (ADC), and DCE pharmacokinetic parameters (K trans and V e ) were calculated from index tumours delineated on the T2W, DW, and DCE images, respectively. The association between the textural features and prostatectomy GS and the MRI-derived parameters, and the utility of the parameters in differentiating between GS 3+4 and 4+3 prostate cancers were assessed statistically. ASM and entropy correlated significantly (p < 0.05) with both GS and median ADC. Contrast correlated moderately with median ADC. The textural features correlated insignificantly with K trans and V e . GS 4+3 cancers had significantly lower ASM and higher entropy than 3+4 cancers, but insignificant differences in median ADC, K trans , and V e . The combined texture-MRI parameters yielded higher classification accuracy (91%) than the individual parameter sets. T2W MRI-derived textural features could serve as potential diagnostic markers, sensitive to the pathological differences in prostate cancers. • T2W MRI-derived textural features correlate significantly with Gleason score and ADC. • T2W MRI-derived textural features differentiate Gleason score 3+4 from 4+3 cancers. • T2W image textural features could augment tumour characterization.

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

A Fast Multiple Sampling Method for Low-Noise CMOS Image Sensors With Column-Parallel 12-bit SAR ADCs

PubMed Central

Kim, Min-Kyu; Hong, Seong-Kwan; Kwon, Oh-Kyong

2015-01-01

This paper presents a fast multiple sampling method for low-noise CMOS image sensor (CIS) applications with column-parallel successive approximation register analog-to-digital converters (SAR ADCs). The 12-bit SAR ADC using the proposed multiple sampling method decreases the A/D conversion time by repeatedly converting a pixel output to 4-bit after the first 12-bit A/D conversion, reducing noise of the CIS by one over the square root of the number of samplings. The area of the 12-bit SAR ADC is reduced by using a 10-bit capacitor digital-to-analog converter (DAC) with four scaled reference voltages. In addition, a simple up/down counter-based digital processing logic is proposed to perform complex calculations for multiple sampling and digital correlated double sampling. To verify the proposed multiple sampling method, a 256 × 128 pixel array CIS with 12-bit SAR ADCs was fabricated using 0.18 μm CMOS process. The measurement results shows that the proposed multiple sampling method reduces each A/D conversion time from 1.2 μs to 0.45 μs and random noise from 848.3 μV to 270.4 μV, achieving a dynamic range of 68.1 dB and an SNR of 39.2 dB. PMID:26712765

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

The Role of Diffusion-Weighted Magnetic Resonance Imaging in the Treatment Response Evaluation of Hepatocellular Carcinoma Patients Treated With Radiation Therapy

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

Yu, Jeong Il; Park, Hee Chul, E-mail: hee.ro.park@skku.edu; Lim, Do Hoon

2014-07-15

Purpose: We investigated the role of diffusion-weighted magnetic resonance imaging (DW MRI) as a response evaluation indicator for hepatocellular carcinoma (HCC) treated with radiation therapy (RT). Methods and Materials: Inclusion criteria of this retrospective study were DW MRI acquisition within 1 month before and 3 to 5 months after RT. In total, 48 patients were enrolled. Two radiation oncologists measured the apparent diffusion coefficient (ADC). Possible predictive factors, including alteration of the ADC value before and 3 to 5 month after RT, in relation to local progression-free survival (LPFS) were analyzed and compared. Results: Three months after RT, 6 patients (12.5%) showed amore » complete response, and 27 patients (56.3%) showed a partial response when evaluated using the modified response evaluation criteria in solid tumors (mRECIST). The average ADC ± SD values were 1.21 ± 0.27 ( × 10{sup −3} mm{sup 2}/s) before and 1.41 ± 0.36 ( × 10{sup −3} mm{sup 2}/s) after RT (P<.001). The most significant prognostic factor related to LPFS was mRECIST (P<.001). The increment of ADC value (≥20%) was also a significant factor (P=.02), but RECIST (version 1.1; P=.11) was not. When RECIST was combined with the increment of ADC value (≥20%), the LPFS rates were significantly different between the groups (P=.004), and the area under the curve value (0.745) was comparable with that of mRECIST (0.765). Conclusions: ADC value change before and after RT in HCC was closely related to LPFS. ADC value and RECIST may substitute for mRECIST in patients who cannot receive contrast agents.« less

Structural studies on the decameric S. typhimurium arginine decarboxylase (ADC): Pyridoxal 5'-phosphate binding induces conformational changes.

PubMed

Deka, G; Bharath, S R; Savithri, H S; Murthy, M R N

2017-09-02

Enteric pathogens such as Salmonella typhimurium colonize the human gut in spite of the lethal acidic pH environment (pH < 2.5) due to the activation of inducible acid tolerance response (ATR) systems. The pyridoxal 5'-phosphate (PLP)-dependent enzyme, biodegradative arginine decarboxylase (ADC, encoded by AdiA), is a component of an ATR system. The enzyme consumes a cytoplasmic proton in the process of arginine degradation to agmatine. Arginine-agmatine antiporter (AdiC) exchanges the product agmatine for arginine. In this manuscript, we describe the structure of Salmonella typhimurium ADC (StADC). The decameric structure assembled from five dimers related by a non crystallographic 5-fold symmetry represents the first apo-form of the enzyme. The structure suggests that PLP-binding is not a prerequisite for oligomerization. Comparison with E. coli ADC reveals that PLP-binding is accompanied by the movement and ordering of two loops (residues 150-159 and 191-197) and a few active site residues such as His256 and Lys257. A number of residues important for substrate binding are disordered in the apo-StADC structure indicating that PLP binding is important for substrate binding. Unlike the interactions between 5-fold related protomers, interactions that stabilize the dimeric structure are not pH dependent. Copyright © 2017 Elsevier Inc. 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

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.

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.

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.

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

PubMed

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

2015-01-01

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

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

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.

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

Temporally resolved electrocardiogram-triggered diffusion-weighted imaging of the human kidney: correlation between intravoxel incoherent motion parameters and renal blood flow at different time points of the cardiac cycle.

PubMed

Wittsack, Hans-Jörg; Lanzman, Rotem S; Quentin, Michael; Kuhlemann, Julia; Klasen, Janina; Pentang, Gael; Riegger, Caroline; Antoch, Gerald; Blondin, Dirk

2012-04-01

To evaluate the influence of pulsatile blood flow on apparent diffusion coefficients (ADC) and the fraction of pseudodiffusion (F(P)) in the human kidney. The kidneys of 6 healthy volunteers were examined by a 3-T magnetic resonance scanner. Electrocardiogram (ECG)-gated and respiratory-triggered diffusion-weighted imaging (DWI) and phase-contrast flow measurements were performed. Flow imaging of renal arteries was carried out to quantify the dependence of renal blood flow on the cardiac cycle. ECG-triggered DWI was acquired in the coronal plane with 16 b values in the range of 0 s/mm(2) and 750 s/mm(2) at the time of minimum (MIN) (20 milliseconds after R wave) and maximum renal blood flow (MAX) (197 ± 24 milliseconds after R wave). The diffusion coefficients were calculated using the monoexponential approach as well as the biexponential intravoxel incoherent motion model and correlated to phase-contrast flow measurements. Flow imaging showed pulsatile renal blood flow depending on the cardiac cycle. The mean flow velocity at MIN was 45 cm/s as compared with 61 cm/s at MAX. F(p) at MIN (0.29) was significantly lower than at MAX (0.40) (P = 0.001). Similarly, ADC(mono), derived from the monoexponential model, also showed a significant difference (P < 0.001) between MIN (ADC(mono) = 2.14 ± 0.08 × 10(-3) mm(2)/s) and MAX (ADC(mono) = 2.37 ± 0.04 × 10(-3) mm(2)/s). The correlation between renal blood flow and F(p) (r = 0.85) as well as ADC(mono) (r = 0.67) was statistically significant. Temporally resolved ECG-gated DWI enables for the determination of the diffusion coefficients at different time points of the cardiac cycle. ADC(mono) and FP vary significantly among acquisitions at minimum (diastole) and maximum (systole) renal blood flow. Temporally resolved ECG-gated DWI might therefore serve as a novel technique for the assessment of pulsatility in the human kidney.

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.

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

Predicting and monitoring response to chemotherapy by 1,3-bis(2-chloroethyl)-1-nitrosourea in subcutaneously implanted 9L glioma using the apparent diffusion coefficient of water and 23Na MRI.

PubMed

Babsky, Andriy M; Hekmatyar, S K; Zhang, Hong; Solomon, James L; Bansal, Navin

2006-07-01

To examine the effects of the alkylating anticancer drug 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) on (23)Na MRI and the water apparent diffusion coefficient (ADC) in subcutaneously- (sc-) implanted 9L glioma in rats. (23)Na MRI and (1)H water ADC measurements were performed on sham-treated control (N = 6) and BCNU-treated (N = 15) Fisher rats one day before BCNU injection and then one, three, and five days after BCNU injection. The BCNU-treated tumors were divided into BCNU-responsive (R(BCNU)) and BCNU-nonresponsive (NR(BCNU)) groups depending on the tumor volume changes that occurred after therapy. The pretreatment (23)Na MRI signal intensity (SI) and water ADC values were higher in R(BCNU) tumors compared to NR(BCNU) tumors. (23)Na MRI SI and water ADC increased with tumor growth in control and NR(BCNU) groups, but these changes were interrupted by BCNU therapy in R(BCNU) group. (23)Na MRI and water ADC measurements may be useful for predicting and monitoring response to chemotherapy in some tumors. However, the changes that occurred in (23)Na MRI SI and water ADC in sc-implanted 9L tumors are in contrast to previously published results for BCNU therapy of orthotopic 9L tumors. This may have important implications for monitoring therapy response in tumors. (c) 2006 Wiley-Liss, Inc.

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

PubMed

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

2016-01-01

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

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.

Endometrial Stromal Sarcoma of the Uterus: Magnetic Resonance Imaging Findings Including Apparent Diffusion Coefficient Value and Its Correlation With Ki-67 Expression.

PubMed

Li, Hai Ming; Liu, Jia; Qiang, Jin Wei; Gu, Wei Yong; Zhang, Guo Fu; Ma, Feng Hua

2017-11-01

This study aimed to investigate the conventional magnetic resonance imaging (MRI) and diffusion-weighted imaging (DWI) features of endometrial stromal sarcoma (ESS) including a preliminary investigation of the correlation between the apparent diffusion coefficient (ADC) value and Ki-67 expression. The clinical and MRI data of 15 patients with ESS confirmed by surgery and pathology were analyzed retrospectively. The conventional MR morphological features, signal intensity on DWI, ADC value (n = 14), and clinicopathological marker Ki-67 (n = 13) were evaluated. Of 15 patients with ESS, 13 tumors were low-grade ESS (LGESS), and the remaining 2 were high-grade ESS (HGESS); 9 tumors were located in the myometrium, 5 were located in the endometrium and/or cervical canal, and 1 was located in extrauterine. Thirteen (87%) of 15 tumors showed a homo- or heterogeneous isointensity on T1-weighted imaging and a heterogeneous hyperintensity on T2-weighted imaging. The hypointense bands were observed in 11 tumors (73%) on T2-weighted imaging. The degenerations (cystic/necrosis/hemorrhage) were observed in 7 LGESS tumors and 2 HGESS tumors. The DWI hyperintensity was observed in 13 tumors (93%) and isointensity in remaining 1. The mean ADC value of the solid components in 14 ESSs was (1.05 ± 0.20) × 10mm/s. The contrast-enhanced MRI showed an obvious enhancement in 14 tumors (93%) (heterogeneous in 7 LGESSs and 2 HGESSs; homogeneous in 5 LGESSs). The ADC value was inversely correlated with the Ki-67 expression (r = -0.613, P = 0.026). Patients with ESS showed some characteristics on conventional MRI and DWI, and there was an inverse correlation between the ADC value and Ki-67 expression.

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.

Performance of Ultrafast DCE-MRI for Diagnosis of Prostate Cancer.

PubMed

Chatterjee, Aritrick; He, Dianning; Fan, Xiaobing; Wang, Shiyang; Szasz, Teodora; Yousuf, Ambereen; Pineda, Federico; Antic, Tatjana; Mathew, Melvy; Karczmar, Gregory S; Oto, Aytekin

2018-03-01

This study aimed to test high temporal resolution dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) for different zones of the prostate and evaluate its performance in the diagnosis of prostate cancer (PCa). Determine whether the addition of ultrafast DCE-MRI improves the performance of multiparametric MRI. Patients (n = 20) with pathologically confirmed PCa underwent preoperative 3T MRI with T2-weighted, diffusion-weighted, and high temporal resolution (~2.2 seconds) DCE-MRI using gadoterate meglumine (Guerbet, Bloomington, IN) without an endorectal coil. DCE-MRI data were analyzed by fitting signal intensity with an empirical mathematical model to obtain parameters: percent signal enhancement, enhancement rate (α), washout rate (β), initial enhancement slope, and enhancement start time along with apparent diffusion coefficient (ADC) and T2 values. Regions of interests were placed on sites of prostatectomy verified malignancy (n = 46) and normal tissue (n = 71) from different zones. Cancer (α = 6.45 ± 4.71 s -1 , β = 0.067 ± 0.042 s -1 , slope = 3.78 ± 1.90 s -1 ) showed significantly (P <.05) faster signal enhancement and washout rates than normal tissue (α = 3.0 ± 2.1 s -1 , β = 0.034 ± 0.050 s -1 , slope = 1.9 ± 1.4 s -1 ), but showed similar percentage signal enhancement and enhancement start time. Receiver operating characteristic analysis showed area under the curve for DCE parameters was comparable to ADC and T2 in the peripheral (DCE 0.67-0.82, ADC 0.80, T2 0.89) and transition zones (DCE 0.61-0.72, ADC 0.69, T2 0.75), but higher in the central zone (DCE 0.79-0.88, ADC 0.45, T2 0.45) and anterior fibromuscular stroma (DCE 0.86-0.89, ADC 0.35, T2 0.12). Importantly, combining DCE with ADC and T2 increased area under the curve by ~30%, further improving the diagnostic accuracy of PCa detection. Quantitative parameters from empirical mathematical model fits to ultrafast DCE-MRI improve diagnosis of PCa. DCE-MRI with higher temporal resolution may capture clinically useful information for PCa diagnosis that would be missed by low temporal resolution DCE-MRI. This new information could improve the performance of multiparametric MRI in PCa detection. Copyright © 2018 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.

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.

A 300-mV 220-nW event-driven ADC with real-time QRS detection for wearable ECG sensors.

PubMed

Zhang, Xiaoyang; Lian, Yong

2014-12-01

This paper presents an ultra-low-power event-driven analog-to-digital converter (ADC) with real-time QRS detection for wearable electrocardiogram (ECG) sensors in wireless body sensor network (WBSN) applications. Two QRS detection algorithms, pulse-triggered (PUT) and time-assisted PUT (t-PUT), are proposed based on the level-crossing events generated from the ADC. The PUT detector achieves 97.63% sensitivity and 97.33% positive prediction in simulation on the MIT-BIH Arrhythmia Database. The t-PUT improves the sensitivity and positive prediction to 97.76% and 98.59% respectively. Fabricated in 0.13 μm CMOS technology, the ADC with QRS detector consumes only 220 nW measured under 300 mV power supply, making it the first nanoWatt compact analog-to-information (A2I) converter with embedded QRS detector.

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

MR Scanner Systems Should Be Adequately Characterized in Diffusion-MRI of the Breast

PubMed Central

Giannelli, Marco; Sghedoni, Roberto; Iacconi, Chiara; Iori, Mauro; Traino, Antonio Claudio; Guerrisi, Maria; Mascalchi, Mario; Toschi, Nicola; Diciotti, Stefano

2014-01-01

Breast imaging represents a relatively recent and promising field of application of quantitative diffusion-MRI techniques. In view of the importance of guaranteeing and assessing its reliability in clinical as well as research settings, the aim of this study was to specifically characterize how the main MR scanner system-related factors affect quantitative measurements in diffusion-MRI of the breast. In particular, phantom acquisitions were performed on three 1.5 T MR scanner systems by different manufacturers, all equipped with a dedicated multi-channel breast coil as well as acquisition sequences for diffusion-MRI of the breast. We assessed the accuracy, inter-scan and inter-scanner reproducibility of the mean apparent diffusion coefficient measured along the main orthogonal directions () as well as of diffusion-tensor imaging (DTI)-derived mean diffusivity (MD) measurements. Additionally, we estimated spatial non-uniformity of (NU) and MD (NUMD) maps. We showed that the signal-to-noise ratio as well as overall calibration of high strength diffusion gradients system in typical acquisition sequences for diffusion-MRI of the breast varied across MR scanner systems, introducing systematic bias in the measurements of diffusion indices. While and MD values were not appreciably different from each other, they substantially varied across MR scanner systems. The mean of the accuracies of measured and MD was in the range [−2.3%,11.9%], and the mean of the coefficients of variation for and MD measurements across MR scanner systems was 6.8%. The coefficient of variation for repeated measurements of both and MD was < 1%, while NU and NUMD values were <4%. Our results highlight that MR scanner system-related factors can substantially affect quantitative diffusion-MRI of the breast. Therefore, a specific quality control program for assessing and monitoring the performance of MR scanner systems for diffusion-MRI of the breast is highly recommended at every site, especially in multicenter and longitudinal studies. PMID:24489711

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

[Value of mDIXON-Quant sequence, diffusion-weighted imaging in quantitatively diagnosing the sacroiliitis stages].

PubMed

An, Y Y; Li, H X; Zhan, Y; Lei, X W

2017-10-10

Objective: To evaluate the value of mDIXON-Quant sequence, diffusion-weighted imaging (DWI) in quantitative diagnosing of the sacroiliitis stages in patients with ankylosing spondylitis (AS). Methods: Based on the Bath Ankylosing Spondylitis Activity Index (BASDAI) and laboratory parameters, a total of 51 patients were diagnosed with AS. They were divided into two groups as early active group ( n =20) and chronic active group ( n =31), and at the same time, 25 healthy people from Tianjin were included as control group. The regular MRI sequences and mDIXON-Quant sequence, DWI were obtained. The apparent diffusion coefficient (ADC) and fat-signal fraction (FF) value of bone marrow with edema of the sacroiliac joints in early active group and chronic active group and of subchondral bone marrow of sacroiliac joint in control group all were measured by ADC maps and FF maps. Mean (FF, ADC) values were compared between groups. Results: The ADC value of the early active group, chronic active group and the control group is (1.07±0.20)×10(-3)mm(2)/s, (1.00±0.22)×10(-3)mm(2)/s, (0.25±0.07)×10(-3)mm(2)/s, respectively, and the differences of ADC value between early active group and control group, chronic active group and control group were significant ( P <0.01), but the difference of the ADC value between early active group and chronic active group was not significant ( P =0.394). That is to say, the ADC value can't distinguish the early active group and chronic active group. The differences of FF value between groups was significant ( P <0.01), and the FF value of bone marrow with edema in chronic active group were higher than that in early active group. Conclusions: The mDIXON-Quant sequence can quantitatively diagnose early active group and chronic active group, and the diagnostic value is better than DWI. Thus, it can provide guidance for clinical treatment and prognosis.

A readout integrated circuit based on DBI-CTIA and cyclic ADC for MEMS-array-based focal plane

NASA Astrophysics Data System (ADS)

Miao, Liu; Dong, Wu; Zheyao, Wang

2016-11-01

A readout integrated circuit (ROIC) for a MEMS (microelectromechanical system)-array-based focal plane (MAFP) intended for imaging applications is presented. The ROIC incorporates current sources for diode detectors, scanners, timing sequence controllers, differential buffered injection-capacitive trans-impedance amplifier (DBI-CTIA) and 10-bit cyclic ADCs, and is integrated with MAFP using 3-D integration technology. A small-signal equivalent model is built to include thermal detectors into circuit simulations. The biasing current is optimized in terms of signal-to-noise ratio and power consumption. Layout design is tailored to fulfill the requirements of 3-D integration and to adapt to the size of MAFP elements, with not all but only the 2 bottom metal layers to complete nearly all the interconnections in DBI-CTIA and ADC in a 40 μm wide column. Experimental chips are designed and fabricated in a 0.35 μm CMOS mixed signal process, and verified in a code density test of which the results indicate a (0.29/-0.31) LSB differential nonlinearity (DNL) and a (0.61/-0.45) LSB integral nonlinearity (INL). Spectrum analysis shows that the effective number of bits (ENOB) is 9.09. The ROIC consumes 248 mW of power at most if not to cut off quiescent current paths when not needed. Project supported by by National Natural Science Foundation of China (No. 61271130), the Beijing Municipal Science and Tech Project (No. D13110100290000), the Tsinghua University Initiative Scientific Research Program (No. 20131089225), and the Shenzhen Science and Technology Development Fund (No. CXZZ20130322170740736).

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

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

Tuning the Formations of Metal-Organic Frameworks by Modification of Ratio of Reactant, Acidity of Reaction System, and Use of a Secondary Ligand

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

Gao, Q; Xie, YB; Li, JR

2012-01-01

Four porous coordination networks (PCNs), {[Zn3O(H2O)(3)(adc)(3)]center dot 2(C2H6NH2)center dot 2(DMF)center dot 3(H2O)}(n) (PCN-131), Zn-2(DMA)(2)(adc)(2)]center dot 2(DMA)}(n) (PCN-132), {[Zn3O(DMF)(adc)(3)(4,4'-bpy)]center dot 2(C2H6NH2)center dot S}(n) (PCN-131'), and {[Zn(adc)(4,4'-bpy)(0.5)]center dot S}(n) (PCN-132'), have been synthesized by the assembly of anthrancene-9,10-dicarboxylic acid (H(2)adc) with Zn(II) under different reaction conditions, including modifications of reactant ratio, acidity variations, and the use of a secondary ligand. Single-crystal X-ray diffraction studies reveal that PCN-131, obtained from the dimethylformamide (DMF) solution under acid condition, has a three-dimentional (3D) framework structure with one-dimensional (1D) honeycomb channels. PCN-132 isolated from dimethylacetamide (DMA) solution without adding acid in synthesis is a two-dimensional (2D)more » layer compound. By employing 4,4'-bipyridyl (4,4'-bpy) as a secondary ligand, PCN-131' and PCN-132' were synchronously synthesized as a mixture outcome with more PCN-131' than PCN-132'. In PCN-131', 4,4'-bpy acting as a secondary ligand is arranged inside the honeycomb channel of the 3D PCN-131, resulting in an effective improvement of thermal stability of the network, while in PCN-132', 4,4'-bpy ligands link 2D layers of PCN-132 to form a pillared-layer 3D framework Gas adsorption has been performed for selected materials. The results show that the framework of PCN-131 is thermally unstable after removing the solvent molecules coordinated to their metal sites. While PCN-131' is stable for gas uptake, with an evaluated Langmuir surface area of 199.04 m(2) g(-1), it shows a selective adsorption of CO2 over CH4.« less

Apparent diffusion coefficient histogram shape analysis for monitoring early response in patients with advanced cervical cancers undergoing concurrent chemo-radiotherapy.

PubMed

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

2016-10-22

To explore the role of apparent diffusion coefficient (ADC) histogram shape related parameters in early assessment of treatment response during the concurrent chemo-radiotherapy (CCRT) course of advanced cervical cancers. This prospective study was approved by the local ethics committee and informed consent was obtained from all patients. Thirty-two patients with advanced cervical squamous cell carcinomas underwent diffusion weighted magnetic resonance imaging (b values, 0 and 800 s/mm 2 ) before CCRT, at the end of 2nd and 4th week during CCRT and immediately after CCRT completion. Whole lesion ADC histogram analysis generated several histogram shape related parameters including skewness, kurtosis, s-sD av , width, standard deviation, as well as first-order entropy and second-order entropies. The averaged ADC histograms of 32 patients were generated to visually observe dynamic changes of the histogram shape following CCRT. All parameters except width and standard deviation showed significant changes during CCRT (all P < 0.05), and their variation trends fell into four different patterns. Skewness and kurtosis both showed high early decline rate (43.10 %, 48.29 %) at the end of 2nd week of CCRT. All entropies kept decreasing significantly since 2 weeks after CCRT initiated. The shape of averaged ADC histogram also changed obviously following CCRT. ADC histogram shape analysis held the potential in monitoring early tumor response in patients with advanced cervical cancers undergoing CCRT.

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.

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

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.

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.

A PFM-based MWIR DROIC employing off-pixel fine conversion of photocharge to digital using integrated column ADCs

NASA Astrophysics Data System (ADS)

Abbasi, S.; Galioglu, A.; Shafique, A.; Ceylan, O.; Yazici, M.; Gurbuz, Y.

2017-02-01

A 32x32 prototype of a digital readout IC (DROIC) for medium-wave infrared focal plane arrays (MWIR IR-FPAs) is presented. The DROIC employs in-pixel photocurrent to digital conversion based on a pulse frequency modulation (PFM) loop and boasts a novel feature of off-pixel residue conversion using 10-bit column SAR ADCs. The remaining charge at the end of integration in typical PFM based digital pixel sensors is usually wasted. Previous works employing in-pixel extended counting methods make use of extra memory and counters to convert this left-over charge to digital, thereby performing fine conversion of the incident photocurrent. This results in a low quantization noise and hence keeps the readout noise low. However, focal plane arrays (FPAs) with small pixel pitch are constrained in pixel area, which makes it difficult to benefit from in-pixel extended counting circuitry. Thus, in this work, a novel approach to measure the residue outside the pixel using column -parallel SAR ADCs has been proposed. Moreover, a modified version of the conventional PFM based pixel has been designed to help hold the residue charge and buffer it to the column ADC. In addition to the 2D array of pixels, the prototype consists of 32 SAR ADCs, a timing controller block and a memory block to buffer the residue data coming out of the ADCs. The prototype has been designed and fabricated in 90nm CMOS.

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.

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.

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.

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.

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.

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.

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

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.

Diffusion-weighted magnetic resonance imaging in autoimmune pancreatitis.

PubMed

Taniguchi, Takao; Kobayashi, Hisato; Nishikawa, Koji; Iida, Etsushi; Michigami, Yoshihiro; Morimoto, Emiko; Yamashita, Rikiya; Miyagi, Ken; Okamoto, Motozumi

2009-04-01

The aim of this study was to investigate the usefulness of diffusion-weighted magnetic resonance imaging (DWI MRI) for the diagnosis and evaluation of autoimmune pancreatitis (AIP). A total of 4 consecutive patients with AIP, 5 patients with chronic alcoholic pancreatitis (CP), and 13 patients without pancreatic disease (controls) were studied. DWI was performed in the axial plane with spin-echo echo-planar imaging single-shot sequence. Apparent diffusion coefficients (ADCs) were measured in circular regions of interest in the pancreas. In AIP patients, abdominal MRI was performed before, and 2-4 weeks after steroid treatment. Follow-up study was performed chronologically for up to 11 months in two patients. The correlation between ADCs of the pancreas and the immunoglobulin G4 (IgG4) index (serum IgG4 value/serum IgG4 value before steroid treatment) was evaluated. In the AIP patients, DWI of the pancreas showed high signal intensity, and the ADCs of the pancreas (mean +/- SD: 0.97 +/- 0.18 x 10(-3) mm(2)/s) were significantly lower than those in patients with CP (1.45 +/- 0.10 x 10(-3) mm(2)/s) or the controls (1.45 +/- 0.16 x 10(-3) mm(2)/s) (Mann-Whitney U-test, P < 0.05). In one AIP patient with focal swelling of the pancreas head that appeared to be a mass, DWI showed high signal intensity throughout the pancreas, indicating diffuse involvement. The ADCs of the pancreas and IgG4 index were significantly inversely correlated (Spearman's rank correlation coefficient, r (s) = -0.80, P < 0.05). Autoimmune pancreatitis showed high signal intensity on DWI, which improved after steroid treatment. ADCs reflected disease activity. Thus, diffusion-weighted MRI might be useful for diagnosing AIP, determining the affected area, and evaluating the effect of treatment.

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.

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.

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.

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.

SU-E-J-136: Multimodality-Image-Based Target Delineation for Dose Painting of Pancreatic Cancer

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

Dalah, E; Paulson, E; Erickson, B

Purpose: Dose escalated RT may provide improved disease local-control for selected unresectable pancreatic cancer. Accurate delineation of the gross tumor volume (GTV) inside pancreatic head or body would allow safe dose escalation considering the tolerances of adjacent organs at risk (OAR). Here we explore the potential of multi-modality imaging (DCE-MRI, ADC-MRI, and FDG-PET) to define the GTV for dose painting of pancreatic cancer. Volumetric variations of DCE-MRI, ADC-MRI and FDG-PET defined GTVs were assessed in comparison to the findings on CT, and to pathology specimens for resectable and borderline reseactable cases of pancreatic cancer. Methods: A total of 19 representativemore » patients with DCE-MRI, ADC-MRI and FDG-PET data were analyzed. Of these, 8 patients had pathological specimens. GTV, inside pancreatic head/neck, or body, were delineated on MRI (denoted GTVDCE, and GTVADC), on FDG-PET using SUV of 2.5, 40% SUVmax, and 50% SUVmax (denoted GTV2.5, GTV40%, and GTV50%). A Kruskal-Wallis test was used to determine whether significant differences existed between GTV volumes. Results: Significant statistical differences were found between the GTVs defined by DCE-MRI, ADC-MRI, and FDG-PET, with a mean and range of 4.73 (1.00–9.79), 14.52 (3.21–25.49), 22.04 (1.00–45.69), 19.10 (4.84–45.59), and 9.80 (0.32–35.21) cm3 (p<0.0001) for GTVDCE, GTVADC, GTV2.5, GTV40%, and GTV50%, respectively. The mean difference and range in the measurements of maximum dimension of GTVs based on DCE-MRI, ADC-MRI, SUV2.5, 40% SUVmax, and 50% SUVmax compared with pathologic specimens were −0.84 (−2.24 to 0.9), 0.41 (−0.15 to 2.3), 0.58 (−1.41 to 3.69), 0.66 (−0.67 to 1.32), and 0.15 (−1.53 to 2.38) cm, respectively. Conclusion: Differences exists between DCE, ADC, and PET defined target volumes for RT of pancreatic cancer. Further studies combined with pathological specimens are required to identify the optimal imaging modality and/or acquisition method to define the GTV.« less

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.

Comparison of diffusion-weighted MRI acquisition techniques for normal pancreas at 3.0 Tesla.

PubMed

Yao, Xiu-Zhong; Kuang, Tiantao; Wu, Li; Feng, Hao; Liu, Hao; Cheng, Wei-Zhong; Rao, Sheng-Xiang; Wang, He; Zeng, Meng-Su

2014-01-01

We aimed to optimize diffusion-weighted imaging (DWI) acquisitions for normal pancreas at 3.0 Tesla. Thirty healthy volunteers were examined using four DWI acquisition techniques with b values of 0 and 600 s/mm2 at 3.0 Tesla, including breath-hold DWI, respiratory-triggered DWI, respiratory-triggered DWI with inversion recovery (IR), and free-breathing DWI with IR. Artifacts, signal-to-noise ratio (SNR) and apparent diffusion coefficient (ADC) of normal pancreas were statistically evaluated among different DWI acquisitions. Statistical differences were noticed in artifacts, SNR, and ADC values of normal pancreas among different DWI acquisitions by ANOVA (P <0.001). Normal pancreas imaging had the lowest artifact in respiratory-triggered DWI with IR, the highest SNR in respiratory-triggered DWI, and the highest ADC value in free-breathing DWI with IR. The head, body, and tail of normal pancreas had statistically different ADC values on each DWI acquisition by ANOVA (P < 0.05). The highest image quality for normal pancreas was obtained using respiratory-triggered DWI with IR. Normal pancreas displayed inhomogeneous ADC values along the head, body, and tail structures.

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.

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%.

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.

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.

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

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

NASA Astrophysics Data System (ADS)

Tapsawat, Wittawat; Sangpet, Teerawat; Kuntanapreeda, Suwat

2018-01-01

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

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.

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.

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

0–0 Energies Using Hybrid Schemes: Benchmarks of TD-DFT, CIS(D), ADC(2), CC2, and BSE/GW formalisms for 80 Real-Life Compounds

PubMed Central

2015-01-01

The 0–0 energies of 80 medium and large molecules have been computed with a large panel of theoretical formalisms. We have used an approach computationally tractable for large molecules, that is, the structural and vibrational parameters are obtained with TD-DFT, the solvent effects are accounted for with the PCM model, whereas the total and transition energies have been determined with TD-DFT and with five wave function approaches accounting for contributions from double excitations, namely, CIS(D), ADC(2), CC2, SCS-CC2, and SOS-CC2, as well as Green’s function based BSE/GW approach. Atomic basis sets including diffuse functions have been systematically applied, and several variations of the PCM have been evaluated. Using solvent corrections obtained with corrected linear-response approach, we found that three schemes, namely, ADC(2), CC2, and BSE/GW allow one to reach a mean absolute deviation smaller than 0.15 eV compared to the measurements, the two former yielding slightly better correlation with experiments than the latter. CIS(D), SCS-CC2, and SOS-CC2 provide significantly larger deviations, though the latter approach delivers highly consistent transition energies. In addition, we show that (i) ADC(2) and CC2 values are extremely close to each other but for systems absorbing at low energies; (ii) the linear-response PCM scheme tends to overestimate solvation effects; and that (iii) the average impact of nonequilibrium correction on 0–0 energies is negligible. PMID:26574326

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.

Post-anoxic quantitative MRI changes may predict emergence from coma and functional outcomes at discharge.

PubMed

Reynolds, Alexandra S; Guo, Xiaotao; Matthews, Elizabeth; Brodie, Daniel; Rabbani, Leroy E; Roh, David J; Park, Soojin; Claassen, Jan; Elkind, Mitchell S V; Zhao, Binsheng; Agarwal, Sachin

2017-08-01

Traditional predictors of neurological prognosis after cardiac arrest are unreliable after targeted temperature management. Absence of pupillary reflexes remains a reliable predictor of poor outcome. Diffusion-weighted imaging has emerged as a potential predictor of recovery, and here we compare imaging characteristics to pupillary exam. We identified 69 patients who had MRIs within seven days of arrest and used a semi-automated algorithm to perform quantitative volumetric analysis of apparent diffusion coefficient (ADC) sequences at various thresholds. Area under receiver operating characteristic curves (ROC-AUC) were estimated to compare predictive values of quantitative MRI with pupillary exam at days 3, 5 and 7 post-arrest, for persistence of coma and functional outcomes at discharge. Cerebral Performance Category scores of 3-4 were considered poor outcome. Excluding patients where life support was withdrawn, ≥2.8% diffusion restriction of the entire brain at an ADC of ≤650×10 -6 m 2 /s was 100% specific and 68% sensitive for failure to wake up from coma before discharge. The ROC-AUC of ADC changes at ≤450×10 -6 mm 2 /s and ≤650×10 -6 mm 2 /s were significantly superior in predicting failure to wake up from coma compared to bilateral absence of pupillary reflexes. Among survivors, >0.01% of diffusion restriction of the entire brain at an ADC ≤450×10 -6 m 2 /s was 100% specific and 46% sensitive for poor functional outcome at discharge. The ROC curve predicting poor functional outcome at ADC ≤450×10 -6 mm 2 /s had an AUC of 0.737 (0.574-0.899, p=0.04). Post-anoxic diffusion changes using quantitative brain MRI may aid in predicting persistent coma and poor functional outcomes at hospital discharge. Copyright © 2017 Elsevier B.V. All rights reserved.

Rapid high resolution T1 mapping as a marker of brain development: Normative ranges in key regions of interest.

PubMed

Eminian, Sylvain; Hajdu, Steven David; Meuli, Reto Antoine; Maeder, Philippe; Hagmann, Patric

2018-01-01

We studied in a clinical setting the age dependent T1 relaxation time as a marker of normal late brain maturation and compared it to conventional techniques, namely the apparent diffusion coefficient (ADC). Forty-two healthy subjects ranging from ages 1 year to 20 years were included in our study. T1 brain maps in which the intensity of each pixel corresponded to T1 relaxation times were generated based on MR imaging data acquired using a MP2RAGE sequence. During the same session, diffusion tensor imaging data was collected. T1 relaxation times and ADC in white matter and grey matter were measured in seven clinically relevant regions of interest and were correlated to subjects' age. In the basal ganglia, there was a small, yet significant, decrease in T1 relaxation time (-0.45 ≤R≤-0.59, p<10-2) and ADC (-0.60≤R≤-0.65, p<10-4) as a function of age. In the frontal and parietal white matter, there was a significant decrease in T1 relaxation time (-0.62≤R≤-0.68, p<10-4) and ADC (-0.81≤R≤-0.85, p<10-4) as a function of age. T1 relaxation time changes in the corpus callosum and internal capsule were less relevant for this age range. There was no significant difference between the correlation of T1 relaxation time and ADC with respect to age (p-value = 0.39). The correlation between T1 relaxation and ADC is strong in the white matter but only moderate in basal ganglia over this age period. T1 relaxation time is a marker of brain maturation or myelination during late brain development. Between the age of 1 and 20 years, T1 relaxation time decreases as a function of age in the white matter and basal ganglia. The greatest changes occur in frontal and parietal white matter. These regions are known to mature in the final stage of development and are mainly composed of association circuits. Age-correlation is not significantly different between T1 relaxation time and ADC. Therefore, T1 relaxation time does not appear to be a superior marker of brain maturation than ADC but may be considered as complementary owing the intrinsic differences in bio-physical sensitivity. This work may serve as normative ranges in clinical imaging routines.

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

NASA Astrophysics Data System (ADS)

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

2017-02-01

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

Pseudo Asynchronous Level Crossing adc for ecg Signal Acquisition.

PubMed

Marisa, T; Niederhauser, T; Haeberlin, A; Wildhaber, R A; Vogel, R; Goette, J; Jacomet, M

2017-02-07

A new pseudo asynchronous level crossing analogue-to-digital converter (adc) architecture targeted for low-power, implantable, long-term biomedical sensing applications is presented. In contrast to most of the existing asynchronous level crossing adc designs, the proposed design has no digital-to-analogue converter (dac) and no continuous time comparators. Instead, the proposed architecture uses an analogue memory cell and dynamic comparators. The architecture retains the signal activity dependent sampling operation by generating events only when the input signal is changing. The architecture offers the advantages of smaller chip area, energy saving and fewer analogue system components. Beside lower energy consumption the use of dynamic comparators results in a more robust performance in noise conditions. Moreover, dynamic comparators make interfacing the asynchronous level crossing system to synchronous processing blocks simpler. The proposed adc was implemented in [Formula: see text] complementary metal-oxide-semiconductor (cmos) technology, the hardware occupies a chip area of 0.0372 mm 2 and operates from a supply voltage of [Formula: see text] to [Formula: see text]. The adc's power consumption is as low as 0.6 μW with signal bandwidth from [Formula: see text] to [Formula: see text] and achieves an equivalent number of bits (enob) of up to 8 bits.

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

Cerebral Blood Flow and Cerebral Edema in Rats With Diabetic Ketoacidosis

PubMed Central

Yuen, Natalie; Anderson, Steven E.; Glaser, Nicole; Tancredi, Daniel J.; O'Donnell, Martha E.

2008-01-01

OBJECTIVE— Cerebral edema (CE) is a potentially life-threatening complication of diabetic ketoacidosis (DKA) in children. Osmotic fluctuations during DKA treatment have been considered responsible, but recent data instead suggest that cerebral hypoperfusion may be involved and that activation of cerebral ion transporters may occur. Diminished cerebral blood flow (CBF) during DKA, however, has not been previously demonstrated. We investigated CBF and edema formation in a rat model of DKA and determined the effects of bumetanide, an inhibitor of Na-K-Cl cotransport. RESEARCH DESIGN AND METHODS— Juvenile rats with streptozotocin-induced DKA were treated with intravenous saline and insulin, similar to human treatment protocols. CBF was determined by magnetic resonance (MR) perfusion–weighted imaging before and during treatment, and CE was assessed by determining apparent diffusion coefficients (ADCs) using MR diffusion–weighted imaging. RESULTS— CBF was significantly reduced in DKA and was responsive to alterations in pCO2. ADC values were reduced, consistent with cell swelling. The reduction in ADCs correlated with dehydration, as reflected in blood urea nitrogen concentrations. Bumetanide caused a rapid rise in ADCs of DKA rats without significantly changing CBF, while saline/insulin caused a rapid rise in CBF and a gradual rise in ADCs. DKA rats treated with bumetanide plus saline/insulin showed a trend toward more rapid rise in cortical ADCs and a larger rise in striatal CBF than those observed with saline/insulin alone. CONCLUSIONS— These data demonstrate that CE in DKA is accompanied by cerebral hypoperfusion before treatment and suggest that blocking Na-K-Cl cotransport may reduce cerebral cell swelling. PMID:18633109

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

Influence of image registration on apparent diffusion coefficient images computed from free-breathing diffusion MR images of the abdomen.

PubMed

Guyader, Jean-Marie; Bernardin, Livia; Douglas, Naomi H M; Poot, Dirk H J; Niessen, Wiro J; Klein, Stefan

2015-08-01

To evaluate the influence of image registration on apparent diffusion coefficient (ADC) images obtained from abdominal free-breathing diffusion-weighted MR images (DW-MRIs). A comprehensive pipeline based on automatic three-dimensional nonrigid image registrations is developed to compensate for misalignments in DW-MRI datasets obtained from five healthy subjects scanned twice. Motion is corrected both within each image and between images in a time series. ADC distributions are compared with and without registration in two abdominal volumes of interest (VOIs). The effects of interpolations and Gaussian blurring as alternative strategies to reduce motion artifacts are also investigated. Among the four considered scenarios (no processing, interpolation, blurring and registration), registration yields the best alignment scores. Median ADCs vary according to the chosen scenario: for the considered datasets, ADCs obtained without processing are 30% higher than with registration. Registration improves voxelwise reproducibility at least by a factor of 2 and decreases uncertainty (Fréchet-Cramér-Rao lower bound). Registration provides similar improvements in reproducibility and uncertainty as acquiring four times more data. Patient motion during image acquisition leads to misaligned DW-MRIs and inaccurate ADCs, which can be addressed using automatic registration. © 2014 Wiley Periodicals, Inc.

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.

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

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

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.

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.

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.

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

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

High fidelity, radiation tolerant analog-to-digital converters

NASA Technical Reports Server (NTRS)

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

2012-01-01

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

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

PubMed

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

2017-03-01

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

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

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.

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.

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.

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.

Diffusion tensor imaging can detect the early stages of cartilage damage: a comparison study.

PubMed

Ukai, Taku; Sato, Masato; Yamashita, Tomohiro; Imai, Yutaka; Mitani, Genya; Takagaki, Tomonori; Serigano, Kenji; Mochida, Joji

2015-02-21

In the present study, we measured damaged areas of cartilage with diffusion tensor (DT) imaging and T2 mapping, and investigated the extent to which cartilage damage could be determined using these techniques. Forty-one patients underwent arthroscopic knee surgery for osteoarthritis of the knee, a meniscus injury, or an anterior cruciate ligament injury. Preoperative magnetic resonance imaging of the knee was performed, including T2 mapping and diffusion tensor imaging. The presence of cartilage injury involving the medial and lateral femoral condyles and tibia plateau was assessed during surgery using the Outerbridge scale. The ADC, T2 values and fractional anisotropy of areas of cartilage injury were then retrospectively analysed. The ADC results identified significant differences between Outerbridge grades 0 and 2 (P = 0.041); 0 and 3 (P < 0.001); 1 and 2 (P = 0.045); 1 and 3 (P < 0.001); and 2 and 3 (P = 0.028). The FA results identified significant differences between grades 0 and 1 (P < 0.001); 0 and 2 (P < 0.001); and 0 and 3 (P < 0.001). T2 mapping identified significant differences between Outerbridge grades 0 and 2 (P = 0.032); 0 and 3 (P < 0.001); 1 and 3 (P < 0.001); and 2 and 3 (P < 0.001). Both the T2 mapping (R(2) = 0.7883) and the ADC (R(2) = 0.9184) correlated significantly with the Outerbridge grade. The FA (R(2) = 0.6616) correlated slightly with the Outerbridge grade. T2 mapping can be useful for detecting moderate or severe cartilage damage, and the ADC can be used to detect early stage cartilage damage. The FA can also distinguish normal from damaged cartilage.

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

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.

Evaluation of different mathematical models and different b-value ranges of diffusion-weighted imaging in peripheral zone prostate cancer detection using b-value up to 4500 s/mm2

PubMed Central

Feng, Zhaoyan; Min, Xiangde; Margolis, Daniel J. A.; Duan, Caohui; Chen, Yuping; Sah, Vivek Kumar; Chaudhary, Nabin; Li, Basen; Ke, Zan; Zhang, Peipei; Wang, Liang

2017-01-01

Objectives To evaluate the diagnostic performance of different mathematical models and different b-value ranges of diffusion-weighted imaging (DWI) in peripheral zone prostate cancer (PZ PCa) detection. Methods Fifty-six patients with histologically proven PZ PCa who underwent DWI-magnetic resonance imaging (MRI) using 21 b-values (0–4500 s/mm2) were included. The mean signal intensities of the regions of interest (ROIs) placed in benign PZs and cancerous tissues on DWI images were fitted using mono-exponential, bi-exponential, stretched-exponential, and kurtosis models. The b-values were divided into four ranges: 0–1000, 0–2000, 0–3200, and 0–4500 s/mm2, grouped as A, B, C, and D, respectively. ADC, , D*, f, DDC, α, Dapp, and Kapp were estimated for each group. The adjusted coefficient of determination (R2) was calculated to measure goodness-of-fit. Receiver operating characteristic curve analysis was performed to evaluate the diagnostic performance of the parameters. Results All parameters except D* showed significant differences between cancerous tissues and benign PZs in each group. The area under the curve values (AUCs) of ADC were comparable in groups C and D (p = 0.980) and were significantly higher than those in groups A and B (p< 0.05 for all). The AUCs of ADC and Kapp in groups B and C were similar (p = 0.07 and p = 0.954), and were significantly higher than the other parameters (p< 0.001 for all). The AUCs of ADC in group D was slightly higher than Kapp (p = 0.002), and both were significantly higher than the other parameters (p< 0.001 for all). Conclusions ADC derived from conventional mono-exponential high b-value (3200 s/mm2) models is an optimal parameter for PZ PCa detection. PMID:28199367

Supply chain optimization at an academic medical center.

PubMed

Labuhn, Jonathan; Almeter, Philip; McLaughlin, Christopher; Fields, Philip; Turner, Benjamin

2017-08-01

A successful supply chain optimization project that leveraged technology, engineering principles, and a technician workflow redesign in the setting of a growing health system is described. With continued rises in medication costs, medication inventory management is increasingly important. Proper management of central pharmacy inventory and floor-stock inventory in automated dispensing cabinets (ADCs) can be challenging. In an effort to improve control of inventory costs in the central pharmacy of a large academic medical center, the pharmacy department implemented a supply chain optimization project in collaboration with the medical center's inhouse team of experts on process improvement and industrial engineering. The project had 2 main components: (1) upgrading and reconfiguring carousel technology within an expanded central pharmacy footprint to generate accurate floor-stock inventory replenishment reports, which resulted in efficiencies within the medication-use system, and (2) implementing a technician workflow redesign and algorithm to right-size the ADC inventory, which decreased inventory stockouts (i.e., incidents of depletion of medication stock) and improved ADC user satisfaction. Through a multifaceted approach to inventory management, the number of stockouts per month was decreased and ADC inventory was optimized, resulting in a one-time inventory cost savings of $220,500. Copyright © 2017 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

LISA phasemeter development

NASA Astrophysics Data System (ADS)

Kullmann, Joachim; Bykov, Iouri; Heinzel, Gerhard; Danzmann, Karsten

The phasemeter is an essentiel component in the measuring chain of the spaceborne gravita-tional wave detector LISA. √ Our goal is to achieve a phasemeter sensitivity of 1 pm/ Hz below 1 Hz with respect to optical signals within a beatnote frequency range of 2 -20 MHz. To get there, several noise sources have to be eliminated. By choosing appropriate filters and adjusting loop gains digital operations of the FPGA-based phase lock loop do not limit the phasemeter sensitivity. One of the main front-end noise sources, the so called ADC time-jitter, is already successfully suppressed by correcting the signal of in-terest by means of a 48 MHz calibration tone. Noise hunting with respect to the analog front-end, currently the most demanding task, is on-going. Recent results will be presented.

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.

Biosynthesis of agmatine in isolated mitochondria and perfused rat liver: studies with 15N-labelled arginine

PubMed Central

2005-01-01

An important but unresolved question is whether mammalian mitochondria metabolize arginine to agmatine by the ADC (arginine decarboxylase) reaction. 15N-labelled arginine was used as a precursor to address this question and to determine the flux through the ADC reaction in isolated mitochondria obtained from rat liver. In addition, liver perfusion system was used to examine a possible action of insulin, glucagon or cAMP on a flux through the ADC reaction. In mitochondria and liver perfusion, 15N-labelled agmatine was generated from external 15N-labelled arginine. The production of 15N-labelled agmatine was time- and dose-dependent. The time-course of [U-15N4]agmatine formation from 2 mM [U-15N4]arginine was best fitted to a one-phase exponential curve with a production rate of approx. 29 pmol·min−1·(mg of protein)−1. Experiments with an increasing concentration (0– 40 mM) of [guanidino-15N2]arginine showed a Michaelis constant Km for arginine of 46 mM and a Vmax of 3.7 nmol·min−1·(mg of protein)−1 for flux through the ADC reaction. Experiments with broken mitochondria showed little changes in Vmax or Km values, suggesting that mitochondrial arginine uptake had little effect on the observed Vmax or Km values. Experiments with liver perfusion demonstrated that over 95% of the effluent agmatine was derived from perfusate [guanidino-15N2]arginine regardless of the experimental condition. However, the output of 15N-labelled agmatine (nmol·min−1·g−1) increased by approx. 2-fold (P<0.05) in perfusions with cAMP. The findings of the present study provide compelling evidence that mitochondrial ADC is present in the rat liver, and suggest that cAMP may stimulate flux through this pathway. PMID:15656789

Age-related differences in the response of the L5-S1 intervertebral disc to spinal traction.

PubMed

Mitchell, Ulrike H; Beattie, Paul F; Bowden, Jennifer; Larson, Robert; Wang, Haonan

2017-10-01

Lumbar traction is a common treatment for low back pain; however its mechanisms of action are poorly understood. It has been hypothesized that a key effect of lumbar traction is its capacity to influence fluid movement within the intervertebral disc (IVD). To determine differences in the apparent diffusion coefficient (ADC) obtained with lumbar diffusion-weighted imaging (DWI) of the L5-S1 IVD before, and during, the application of lumbar traction. Case series, repeated measures. A static traction load of ∼50% of body-weight was applied to the low back using a novel "MRI-safe" apparatus. DWI of the lumbar spine was performed prior to, and during the application of the traction load. Participants were currently asymptomatic and included a young adult group (n = 18) and a middle-aged group (n = 15). The young adult group had a non-significant 2.2% increase in ADC (mean change = 0.03 × 10 -3  mm 2 /s, SD = 0.24, 95% CI = -0.09, 0.15). The ADC for the middle-aged group significantly increased by 20% (mean change of 0.18 × 10 -3  mm 2 /s, SD = 0.19; 95% CI = 0.07, 0.28; p = 0.003; effect size = 0.95). There was an inverse relationship between the ADC obtained before traction and the percent increase in ADC that was measured during traction. Static traction was associated with an increase in diffusion of water within the L5-S1 IVDs of middle-age individuals, but not in young adults, suggesting age-related differences in the diffusion response. Further study is needed to assess the relationship between these findings and the symptoms of back pain. 4. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

PubMed

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

2018-06-01

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

Design of a portable, intrinsically safe multichannel acquisition system for high-resolution, real-time processing HD-sEMG.

PubMed

Barone, Umberto; Merletti, Roberto

2013-08-01

A compact and portable system for real-time, multichannel, HD-sEMG acquisition is presented. The device is based on a modular, multiboard approach for scalability and to optimize power consumption for battery operating mode. The proposed modular approach allows us to configure the number of sEMG channels from 64 to 424. A plastic-optical-fiber-based 10/100 Ethernet link is implemented on a field-programmable gate array (FPGA)-based board for real-time, safety data transmission toward a personal computer or laptop for data storage and offline analysis. The high-performance A/D conversion stage, based on 24-bit ADC, allows us to automatically serialize the samples and transmits them on a single SPI bus connecting a sequence of up to 14 ADC chips in chain mode. The prototype is configured to work with 64 channels and a sample frequency of 2.441 ksps (derived from 25-MHz clock source), corresponding to a real data throughput of 3 Mbps. The prototype was assembled to demonstrate the available features (e.g., scalability) and evaluate the expected performances. The analog front end board could be dynamically configured to acquire sEMG signals in monopolar or single differential mode by means of FPGA I/O interface. The system can acquire continuously 64 channels for up to 5 h with a lightweight battery pack of 7.5 Vdc/2200 mAh. A PC-based application was also developed, by means of the open source Qt Development Kit from Nokia, for prototype characterization, sEMG measurements, and real-time visualization of 2-D maps.

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

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.

Diffusion-weighted magnetic resonance imaging and apparent diffusion coefficient mapping for diagnosing infectious spondylodiscitis: a preliminary study.

PubMed

Chen, Tai-Yuan; Wu, Te-Chang; Tsui, Yu-Kun; Chen, Hou-Hsun; Lin, Chien-Jen; Lee, Huey-Jen; Wu, Tai-Ching

2015-01-01

Though diffusion-weighted (DW) magnetic resonance imaging (MRI) is useful for diagnosing many pathologies, its use in infectious spondylodiscitis is unclear. We aimed to evaluate the use of DW MRI and apparent diffusion coefficient (ADC) mapping for the diagnosis of infectious spondylodiscitis. In this retrospective study, 17 patients with confirmed infectious spondylodiscitis were matched by age and level of infected disc with 17 patients with degenerative disc disease (DDD) and 17 healthy controls. All patients received conventional MRI and diffusion-weighted imaging (DWI) in the same imaging session. ADC values of the 3 groups of patients were compared. The mean age of each group was 67.4 ± 11.6 years. The mean ADCs of the normal control, DDD, and infectious spondylodiscitis groups were 1.76 ± 0.19 × 10(-3) , 1.12 ± 0.22 × 10(-3) , and 1.27 ± 0.38 × 10(-3) mm2 /second, respectively. The ADCs of the DDD and infectious spondylodiscitis groups were both significantly lower than that of the normal control group (both, P < 0.001). These data suggest that DWI/ADC MRI may be useful in the early diagnosis of infectious spondylodiscitis. © 2014 The Authors. Journal of Neuroimaging published by Wiley Periodicals, Inc. on behalf of American Society of Neuroimaging.

An all-silica three element wide-field corrector for GMT

NASA Astrophysics Data System (ADS)

Saunders, Will; Gillingham, Peter; Lin, Sean; Woodruff, Bob; Rakich, Andrew

2016-08-01

We present an alternative Corrector-ADC design for GMT. The design consists of just 3 silica lenses, of maximum size 1.51m, and includes only a single low-precision asphere for 20' field-of-view, and none for 10'. The polychromatic (360nm-1300nm) image quality is d80<0.043" at zenith and d80<0.20" for ZD<60 degrees. The monochromatic image quality is d80<0.1" everywhere, and typically 0.05". The ADC action is achieved by tilt and translation of all three lenses; L1 and L2 via simple slide mechanisms each using a single encoded actuator, and L3 via a novel `tracker-ball' support and three actuators. There is also a small motion of M2 via the hexapod, automatically generated by the AGWS system. The ADC action causes a small non-telecentricity, but this is much less than the unavoidable chromatic effects shared with the baseline design. The ADC action also changes the distortion pattern of the telescope, but this can be used positively, to reduce the maximum image motion due to differential refraction by a factor of three. The transmission is superb at all wavelengths, because of the reduced number of air/glass surfaces, and the use only of fused silica.

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.

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.

Demonstration of the reproducibility of free-breathing diffusion-weighted MRI and dynamic contrast enhanced MRI in children with solid tumours: a pilot study.

PubMed

Miyazaki, Keiko; Jerome, Neil P; Collins, David J; Orton, Matthew R; d'Arcy, James A; Wallace, Toni; Moreno, Lucas; Pearson, Andrew D J; Marshall, Lynley V; Carceller, Fernando; Leach, Martin O; Zacharoulis, Stergios; Koh, Dow-Mu

2015-09-01

The objectives are to examine the reproducibility of functional MR imaging in children with solid tumours using quantitative parameters derived from diffusion-weighted (DW-) and dynamic contrast enhanced (DCE-) MRI. Patients under 16-years-of age with confirmed diagnosis of solid tumours (n = 17) underwent free-breathing DW-MRI and DCE-MRI on a 1.5 T system, repeated 24 hours later. DW-MRI (6 b-values, 0-1000 sec/mm(2)) enabled monoexponential apparent diffusion coefficient estimation using all (ADC0-1000) and only ≥100 sec/mm(2) (ADC100-1000) b-values. DCE-MRI was used to derive the transfer constant (K(trans)), the efflux constant (kep), the extracellular extravascular volume (ve), and the plasma fraction (vp), using a study cohort arterial input function (AIF) and the extended Tofts model. Initial area under the gadolinium enhancement curve and pre-contrast T1 were also calculated. Percentage coefficients of variation (CV) of all parameters were calculated. The most reproducible cohort parameters were ADC100-1000 (CV = 3.26%), pre-contrast T1 (CV = 6.21%), and K(trans) (CV = 15.23%). The ADC100-1000 was more reproducible than ADC0-1000, especially extracranially (CV = 2.40% vs. 2.78%). The AIF (n = 9) derived from this paediatric population exhibited sharper and earlier first-pass and recirculation peaks compared with the literature's adult population average. Free-breathing functional imaging protocols including DW-MRI and DCE-MRI are well-tolerated in children aged 6 - 15 with good to moderate measurement reproducibility. • Diffusion MRI protocol is feasible and well-tolerated in a paediatric oncology population. • DCE-MRI for pharmacokinetic evaluation is feasible and well tolerated in a paediatric oncology population. • Paediatric arterial input function (AIF) shows systematic differences from the adult population-average AIF. • Variation of quantitative parameters from paired functional MRI measurements were within 20%.

A 24-Week, Open-Label Extension Study to Investigate the Long-term Safety, Tolerability, and Efficacy of 13.3 mg/24 h Rivastigmine Patch in Patients With Severe Alzheimer Disease.

PubMed

Farlow, Martin R; Grossberg, George T; Sadowsky, Carl H; Meng, Xiangyi; Velting, Drew M

2015-01-01

The long-term safety, tolerability, and efficacy of high-dose 13.3 mg/24 h rivastigmine patch in severe Alzheimer disease was evaluated in a 24-week, open-label extension to the double-blind ACTION study. Safety and tolerability, and efficacy on the Alzheimer's Disease Cooperative Study-Activities of Daily Living scale-Severe Impairment Version (ADCS-ADL-SIV), Severe Impairment Battery (SIB), and ADCS-Clinical Global Impression of Change (ADCS-CGIC) were assessed. Overall, 197 patients continued on 13.3 mg/24 h patch; 199 uptitrated from 4.6 mg/24 h to 13.3 mg/24 h patch. The incidence of adverse events (AEs), serious AEs and discontinuations due to AEs was similar in patients who continued on, and patients who uptitrated to, 13.3 mg/24 h patch (AEs: 57.9% and 59.8%; serious AEs: 16.2% and 16.1%; discontinuations: 11.2% and 12.1%, respectively). Larger mean changes from double-blind baseline were observed in patients uptitrated on the ADCS-ADL-SIV (-4.6; SD=8.7) and SIB (-7.0; SD=16.6), than those who continued on 13.3 mg/24 h patch (-3.9; SD=8.0 and -4.7; SD=16.8, respectively). ADCS-CGIC scores were comparable. There were no clinically relevant between-group differences in safety and tolerability. Greater decline was observed in patients with delayed uptitration to high-dose 13.3 mg/24 h patch than patients who continued on high-dose patch.

Assessment of MRI Parameters as Imaging Biomarkers for Radiation Necrosis in the Rat Brain

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

Wang Silun; Tryggestad, Erik; Zhou Tingting

Purpose: Radiation necrosis is a major complication of radiation therapy. We explore the features of radiation-induced brain necrosis in the rat, using multiple MRI approaches, including T{sub 1}, T{sub 2}, apparent diffusion constant (ADC), cerebral blood flow (CBF), magnetization transfer ratio (MTR), and amide proton transfer (APT) of endogenous mobile proteins and peptides. Methods and Materials: Adult rats (Fischer 344; n = 15) were irradiated with a single, well-collimated X-ray beam (40 Gy; 10 Multiplication-Sign 10 mm{sup 2}) in the left brain hemisphere. MRI was acquired on a 4.7-T animal scanner at {approx}25 weeks' postradiation. The MRI signals of necroticmore » cores and perinecrotic regions were assessed with a one-way analysis of variance. Histological evaluation was accomplished with hematoxylin and eosin staining. Results: ADC and CBF MRI could separate perinecrotic and contralateral normal brain tissue (p < 0.01 and < 0.05, respectively), whereas T{sub 1}, T{sub 2}, MTR, and APT could not. MRI signal intensities were significantly lower in the necrotic core than in normal brain for CBF (p < 0.001) and APT (p < 0.01) and insignificantly higher or lower for T{sub 1}, T{sub 2}, MTR, and ADC. Histological results demonstrated coagulative necrosis within the necrotic core and reactive astrogliosis and vascular damage within the perinecrotic region. Conclusion: ADC and CBF are promising imaging biomarkers for identifying perinecrotic regions, whereas CBF and APT are promising for identifying necrotic cores.« less

Assessment of MRI parameters as imaging biomarkers for radiation necrosis in the rat brain.

PubMed

Wang, Silun; Tryggestad, Erik; Zhou, Tingting; Armour, Michael; Wen, Zhibo; Fu, De-Xue; Ford, Eric; van Zijl, Peter C M; Zhou, Jinyuan

2012-07-01

Radiation necrosis is a major complication of radiation therapy. We explore the features of radiation-induced brain necrosis in the rat, using multiple MRI approaches, including T(1), T(2), apparent diffusion constant (ADC), cerebral blood flow (CBF), magnetization transfer ratio (MTR), and amide proton transfer (APT) of endogenous mobile proteins and peptides. Adult rats (Fischer 344; n = 15) were irradiated with a single, well-collimated X-ray beam (40 Gy; 10 × 10 mm(2)) in the left brain hemisphere. MRI was acquired on a 4.7-T animal scanner at ~25 weeks' postradiation. The MRI signals of necrotic cores and perinecrotic regions were assessed with a one-way analysis of variance. Histological evaluation was accomplished with hematoxylin and eosin staining. ADC and CBF MRI could separate perinecrotic and contralateral normal brain tissue (p < 0.01 and < 0.05, respectively), whereas T(1), T(2), MTR, and APT could not. MRI signal intensities were significantly lower in the necrotic core than in normal brain for CBF (p < 0.001) and APT (p < 0.01) and insignificantly higher or lower for T(1), T(2), MTR, and ADC. Histological results demonstrated coagulative necrosis within the necrotic core and reactive astrogliosis and vascular damage within the perinecrotic region. ADC and CBF are promising imaging biomarkers for identifying perinecrotic regions, whereas CBF and APT are promising for identifying necrotic cores. Copyright © 2012 Elsevier Inc. All rights reserved.

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.

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.

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.

Differentiation of Central Lung Cancer from Atelectasis: Comparison of Diffusion-Weighted MRI with PET/CT

PubMed Central

Yang, Rui-Meng; Li, Long; Wei, Xin-Hua; Guo, Yong-Mei; Huang, Yun-Hai; Lai, Li-Sha; Chen, A-Mei; Liu, Guo-Shun; Xiong, Wei-Feng; Luo, Liang-Ping; Jiang, Xin-Qing

2013-01-01

Objective Prospectively assess the performance of diffusion-weighted magnetic resonance imaging (DW-MRI) for differentiation of central lung cancer from atelectasis. Materials and Methods 38 consecutive lung cancer patients (26 males, 12 females; age range: 28–71 years; mean age: 49 years) who were referred for thoracic MR imaging examinations were enrolled. MR examinations were performed using a 1.5-T clinical scanner and scanning sequences of T1WI, T2WI, and DWI. Cancers and atelectasis were measured by mapping of the apparent diffusion coefficients (ADCs) obtained with a b-value of 500 s/mm2. Results PET/CT and DW-MR allowed differentiation of tumor and atelectasis in all 38 cases, but T2WI did not allow differentiation in 9 cases. Comparison of conventional T2WI and DW-MRI indicated a higher contrast noise ratio of the central lung carcinoma than the atelectasis by DW-MRI. ADC maps indicated significantly lower mean ADC in the central lung carcinoma than in the atelectasis (1.83±0.58 vs. 2.90±0.26 mm2/s, p<0.0001). ADC values of small cell lung carcinoma were significantly greater than those from squamous cell carcinoma and adenocarcinoma (p<0.0001 for both). Conclusions DW-MR imaging provides valuable information not obtained by conventional MR and may be useful for differentiation of central lung carcinoma from atelectasis. Future developments may allow DW-MR imaging to be used as an alternative to PET-CT in imaging of patients with lung cancer. PMID:23593186

Diffusion-weighted MR imaging in thymic epithelial tumors: correlation with World Health Organization classification and clinical staging.

PubMed

Abdel Razek, Ahmed Abdel Khalek; Khairy, Mohamed; Nada, Nadia

2014-10-01

To assess thymic epithelial tumors with diffusion-weighted magnetic resonance (MR) imaging. Informed consent from patients and institutional review board approval were obtained. Prospective study was conducted on 30 consecutive patients (21 men and nine women; age range, 35-71 years) with thymic epithelial tumors. They underwent true fast imaging with steady-state precession and single-shot echo-planar diffusion-weighted MR imaging of the mediastinum with b values of 0, 400, and 800 sec/mm(2). Apparent diffusion coefficient (ADC) of the thymic epithelial tumors was calculated by the same observer at two settings and was correlated with World Health Organization classification and clinical staging. There was significant difference in longest diameter (P = .001) and necrotic part of the tumor (P = .014) between low-risk thymoma, high-risk thymoma, and thymic carcinoma. Mean ADC value of both readings of thymic epithelial tumors (n = 30) was 1.24 × 10(-3) mm(2)/sec and 1.22 × 10(-3) mm(2)/sec, with good intraobserver agreement (κ = 0.732). There was significant difference in both readings (P = .01 and .20) of low-risk thymoma (1.30 × 10(-3) mm(2)/sec and 1.29 × 10(-3) mm(2)/sec), high-risk thymoma (1.16 × 10(-3) mm(2)/sec and 1.14 × 10(-3) mm(2)/sec), and thymic carcinoma (1.18 × 10(-3) mm(2)/sec and 1.06 × 10(-3) mm(2)/sec). Cutoff ADC values of both readings used to differentiate low-risk thymoma from high-risk thymoma and thymic carcinoma were 1.25 and 1.22 × 10(-3) mm(2)/sec with area under the curve of 0.804 and 0.851, respectively. There was significant difference in both readings of ADC value of early (stage I, II) and advanced stages (stage III, IV) of thymic epithelial tumors (P = .006 and .005, respectively). ADC value is a noninvasive, reliable, and reproducible imaging parameter that may help to assess and characterize thymic epithelial tumors. © RSNA, 2014.

A 12-bit high-speed column-parallel two-step single-slope analog-to-digital converter (ADC) for CMOS image sensors.

PubMed

Lyu, Tao; Yao, Suying; Nie, Kaiming; Xu, Jiangtao

2014-11-17

A 12-bit high-speed column-parallel two-step single-slope (SS) analog-to-digital converter (ADC) for CMOS image sensors is proposed. The proposed ADC employs a single ramp voltage and multiple reference voltages, and the conversion is divided into coarse phase and fine phase to improve the conversion rate. An error calibration scheme is proposed to correct errors caused by offsets among the reference voltages. The digital-to-analog converter (DAC) used for the ramp generator is based on the split-capacitor array with an attenuation capacitor. Analysis of the DAC's linearity performance versus capacitor mismatch and parasitic capacitance is presented. A prototype 1024 × 32 Time Delay Integration (TDI) CMOS image sensor with the proposed ADC architecture has been fabricated in a standard 0.18 μm CMOS process. The proposed ADC has average power consumption of 128 μW and a conventional rate 6 times higher than the conventional SS ADC. A high-quality image, captured at the line rate of 15.5 k lines/s, shows that the proposed ADC is suitable for high-speed CMOS image sensors.

Fast and Analytical EAP Approximation from a 4th-Order Tensor.

PubMed

Ghosh, Aurobrata; Deriche, Rachid

2012-01-01

Generalized diffusion tensor imaging (GDTI) was developed to model complex apparent diffusivity coefficient (ADC) using higher-order tensors (HOTs) and to overcome the inherent single-peak shortcoming of DTI. However, the geometry of a complex ADC profile does not correspond to the underlying structure of fibers. This tissue geometry can be inferred from the shape of the ensemble average propagator (EAP). Though interesting methods for estimating a positive ADC using 4th-order diffusion tensors were developed, GDTI in general was overtaken by other approaches, for example, the orientation distribution function (ODF), since it is considerably difficult to recuperate the EAP from a HOT model of the ADC in GDTI. In this paper, we present a novel closed-form approximation of the EAP using Hermite polynomials from a modified HOT model of the original GDTI-ADC. Since the solution is analytical, it is fast, differentiable, and the approximation converges well to the true EAP. This method also makes the effort of computing a positive ADC worthwhile, since now both the ADC and the EAP can be used and have closed forms. We demonstrate our approach with 4th-order tensors on synthetic data and in vivo human data.

Fast and Analytical EAP Approximation from a 4th-Order Tensor

PubMed Central

Ghosh, Aurobrata; Deriche, Rachid

2012-01-01

Generalized diffusion tensor imaging (GDTI) was developed to model complex apparent diffusivity coefficient (ADC) using higher-order tensors (HOTs) and to overcome the inherent single-peak shortcoming of DTI. However, the geometry of a complex ADC profile does not correspond to the underlying structure of fibers. This tissue geometry can be inferred from the shape of the ensemble average propagator (EAP). Though interesting methods for estimating a positive ADC using 4th-order diffusion tensors were developed, GDTI in general was overtaken by other approaches, for example, the orientation distribution function (ODF), since it is considerably difficult to recuperate the EAP from a HOT model of the ADC in GDTI. In this paper, we present a novel closed-form approximation of the EAP using Hermite polynomials from a modified HOT model of the original GDTI-ADC. Since the solution is analytical, it is fast, differentiable, and the approximation converges well to the true EAP. This method also makes the effort of computing a positive ADC worthwhile, since now both the ADC and the EAP can be used and have closed forms. We demonstrate our approach with 4th-order tensors on synthetic data and in vivo human data. PMID:23365552

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.

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.

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.

Cancer, immunodeficiency and antiretroviral treatment: results from the Australian HIV Observational Database (AHOD).

PubMed

Petoumenos, K; van Leuwen, M T; Vajdic, C M; Woolley, I; Chuah, J; Templeton, D J; Grulich, A E; Law, M G

2013-02-01

The objective of the study was to conduct a within-cohort assessment of risk factors for incident AIDS-defining cancers (ADCs) and non-ADCs (NADCs) within the Australian HIV Observational Database (AHOD). A total of 2181 AHOD registrants were linked to the National AIDS Registry/National HIV Database (NAR/NHD) and the Australian Cancer Registry to identify those with a notified cancer diagnosis. Included in the current analyses were cancers diagnosed after HIV infection. Risk factors for cancers were also assessed using logistic regression methods. One hundred and thirty-nine cancer cases were diagnosed after HIV infection among 129 patients. More than half the diagnoses (n = 68; 60%) were ADCs, of which 69% were Kaposi's sarcoma and 31% non-Hodgkin's lymphoma. Among the NADCs, the most common cancers were melanoma (n = 10), lung cancer (n = 6), Hodgkin's lymphoma (n = 5) and anal cancer (n = 5). Over a total of 21021 person-years (PY) of follow-up since HIV diagnosis, the overall crude cancer incidence rate for any cancer was 5.09/1000 PY. The overall rate of cancers decreased from 15.9/1000 PY [95% confidence interval (CI) 9.25-25.40/1000 PY] for CD4 counts < 100 cells/μL to 2.4/1000 PY (95% CI 1.62-3.39/1000 PY) for CD4 counts > 350 cells/μL. Lower CD4 cell count and prior AIDS diagnoses were significant predictors for both ADCs and NADCs. ADCs remain the predominant cancers in this population, although NADC rates have increased in the more recent time period. Immune deficiency is a risk factor for both ADCs and NADCs. © 2012 British HIV Association.

MR diffusion tensor imaging of normal kidneys.

PubMed

Wang, Wen-juan; Pui, Margaret H; Guo, Yan; Hu, Xiao-shu; Wang, Huan-jun; Yang, Dong

2014-11-01

To assess the feasibility of diffusion tensor imaging (DTI) of normal kidneys and the influence of hydration state. Ten healthy volunteers underwent renal DTI after fasting for 12 hours and 4 hours, without fasting, and following water diuresis. Medullary and cortical apparent diffusion coefficient (ADC) and fractional anisotropy (FA) values were measured and compared in the four different states of hydration. DTI was performed with a 3T magnetic resonance imaging (MRI) system using fat-saturated single-shot spin-echo echo planar imaging sequence. ADC of normal cortex (2.387 ± 0.081 × 10(-3) mm(2) /s) was significantly higher (t = 20.126, P = 0) than that of medulla (1.990 ± 0.063 × 10(-3) mm(2) /s). The FA value of normal cortex (0.282 ± 0.017) was significantly lower (t = -42.713, P = 0) than that of medulla (0.447 ± 0.022). The ADC and FA values of the left renal cortex (2.404 ± 0.082 × 10(-3) mm(2) /s, 0.282 ± 0.017) and medulla (2.002 ± 0.081 × 10(-3) mm(2) /s, 0.452 ± 0.024) were not significantly different (P > 0.05) from those of right renal cortex (2.369 ± 0.080 × 10(-3) mm(2) /s, 0.283 ± 0.018) and medulla (1.978 ± 0.039 × 10(-3) mm(2) /s, 0.443 ± 0.019). Values for ADC (×10(-3) mm(2) /s) and FA in the 12-hour fasting, 4-hour fasting, nonfasting, and water diuresis states were 2.372 ± 0.095 and 0.278 ± 0.018, 2.387 ± 0.081 and 0.282 ± 0.017, 2.416 ± 0.051 and 0.279 ± 0.023, 2.421 ± 0.068, and 0.270 ± 0.021, respectively, in cortex, 1.972 ± 0.084 and 0.438 ± 0.014, 1.990 ± 0.063 and 0.447 ± 0.022, 2.021 ± 0.081 and 0.450 ± 0.031, 2.016 ± 0.076 and 0.449 ± 0.028, respectively, in medulla. The ADC and FA values in different hydration states were not significantly different (P > 0.05). DTI of normal kidneys is feasible with reproducible ADC and FA values independent of hydration states. © 2013 Wiley Periodicals, Inc.

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

PubMed

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

2017-07-25

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

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

Minimal-post-processing 320-Gbps true random bit generation using physical white chaos.

PubMed

Wang, Anbang; Wang, Longsheng; Li, Pu; Wang, Yuncai

2017-02-20

Chaotic external-cavity semiconductor laser (ECL) is a promising entropy source for generation of high-speed physical random bits or digital keys. The rate and randomness is unfortunately limited by laser relaxation oscillation and external-cavity resonance, and is usually improved by complicated post processing. Here, we propose using a physical broadband white chaos generated by optical heterodyning of two ECLs as entropy source to construct high-speed random bit generation (RBG) with minimal post processing. The optical heterodyne chaos not only has a white spectrum without signature of relaxation oscillation and external-cavity resonance but also has a symmetric amplitude distribution. Thus, after quantization with a multi-bit analog-digital-convertor (ADC), random bits can be obtained by extracting several least significant bits (LSBs) without any other processing. In experiments, a white chaos with a 3-dB bandwidth of 16.7 GHz is generated. Its entropy rate is estimated as 16 Gbps by single-bit quantization which means a spectrum efficiency of 96%. With quantization using an 8-bit ADC, 320-Gbps physical RBG is achieved by directly extracting 4 LSBs at 80-GHz sampling rate.

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.

Prediction of malignancy by a radiomic signature from contrast agent-free diffusion MRI in suspicious breast lesions found on screening mammography.

PubMed

Bickelhaupt, Sebastian; Paech, Daniel; Kickingereder, Philipp; Steudle, Franziska; Lederer, Wolfgang; Daniel, Heidi; Götz, Michael; Gählert, Nils; Tichy, Diana; Wiesenfarth, Manuel; Laun, Frederik B; Maier-Hein, Klaus H; Schlemmer, Heinz-Peter; Bonekamp, David

2017-08-01

To assess radiomics as a tool to determine how well lesions found suspicious on breast cancer screening X-ray mammography can be categorized into malignant and benign with unenhanced magnetic resonance (MR) mammography with diffusion-weighted imaging and T 2 -weighted sequences. From an asymptomatic screening cohort, 50 women with mammographically suspicious findings were examined with contrast-enhanced breast MRI (ceMRI) at 1.5T. Out of this protocol an unenhanced, abbreviated diffusion-weighted imaging protocol (ueMRI) including T 2 -weighted, (T 2 w), diffusion-weighted imaging (DWI), and DWI with background suppression (DWIBS) sequences and corresponding apparent diffusion coefficient (ADC) maps were extracted. From ueMRI-derived radiomic features, three Lasso-supervised machine-learning classifiers were constructed and compared with the clinical performance of a highly experienced radiologist: 1) univariate mean ADC model, 2) unconstrained radiomic model, 3) constrained radiomic model with mandatory inclusion of mean ADC. The unconstrained and constrained radiomic classifiers consisted of 11 parameters each and achieved differentiation of malignant from benign lesions with a .632 + bootstrap receiver operating characteristics (ROC) area under the curve (AUC) of 84.2%/85.1%, compared to 77.4% for mean ADC and 95.9%/95.9% for the experienced radiologist using ceMRI/ueMRI. In this pilot study we identified two ueMRI radiomics classifiers that performed well in the differentiation of malignant from benign lesions and achieved higher performance than the mean ADC parameter alone. Classification was lower than the almost perfect performance of a highly experienced breast radiologist. The potential of radiomics to provide a training-independent diagnostic decision tool is indicated. A performance reaching the human expert would be highly desirable and based on our results is considered possible when the concept is extended in larger cohorts with further development and validation of the technique. 1 Technical Efficacy: Stage 2 J. MAGN. RESON. IMAGING 2017;46:604-616. © 2017 International Society for Magnetic Resonance in Medicine.

Single- or multi-flavor Kondo effect in graphene

NASA Astrophysics Data System (ADS)

Zhu, Zhen-Gang; Ding, Kai-He; Berakdar, Jamal

2010-06-01

Based on the tight-binding formalism, we investigate the Anderson and the Kondo model for an adatom magnetic impurity above graphene. Different impurity positions are analyzed. Employing a partial-wave representation we study the nature of the coupling between the impurity and the conducting electrons. The components from the two Dirac points are mixed while interacting with the impurity. Two configurations are considered explicitly: the adatom is above one atom (ADA), the other case is the adatom above the center the honeycomb (ADC). For ADA the impurity is coupled with one flavor for both A and B sublattice and both Dirac points. For ADC the impurity couples with multi-flavor states for a spinor state of the impurity. We show, explicitly for a 3d magnetic atom, dz2, (dxz,dyz), and (dx2- y2,dxy) couple respectively with the Γ1, Γ5(E1), and Γ6(E2) representations (reps) of C6v group in ADC case. The bases for these reps of graphene are also derived explicitly. For ADA we calculate the Kondo temperature.

Functional decline in the elderly with MCI: Cultural adaptation of the ADCS-ADL scale.

PubMed

Cintra, Fabiana Carla Matos da Cunha; Cintra, Marco Túlio Gualberto; Nicolato, Rodrigo; Bertola, Laiss; Ávila, Rafaela Teixeira; Malloy-Diniz, Leandro Fernandes; Moraes, Edgar Nunes; Bicalho, Maria Aparecida Camargos

2017-07-01

Translate, transcultural adaptation and application to Brazilian Portuguese of the Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL) scale as a cognitive screening instrument. We applied the back translation added with pretest and bilingual methods. The sample was composed by 95 elderly individuals and their caregivers. Thirty-two (32) participants were diagnosed as mild cognitive impairment (MCI) patients, 33 as Alzheimer's disease (AD) patients and 30 were considered as cognitively normal individuals. There were only little changes on the scale. The Cronbach alpha coefficient was 0.89. The scores were 72.9 for control group, followed by MCI (65.1) and by AD (55.9), with a p-value < 0.001. The ROC curve value was 0.89. We considered a cut point of 72 and we observed a sensibility of 86.2%, specificity of 70%, positive predictive value of 86.2%, negative predictive value of 70%, positive likelihood ratio of 2.9 and negative likelihood ratio of 0.2. ADCS-ADL scale presents satisfactory psychometric properties to discriminate between MCI, AD and normal cognition.

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.

RESULTS OF A PILOT FIELD STUDY TO EVALUATE THE EFFECTIVENESS OF CLEANING RESIDENTIAL HEATING AND AIR-CONDITIONING SYSTEMS AND THE IMPACT ON INDOOR AIR QUALITY AND SYSTEM PERFORMANCE

EPA Science Inventory

The report discusses and gives results of a pilot field study to evaluate the effectiveness of air duct cleaning (ADC) as a source removal technique in residential heating and air-conditioning (HAC) systems and its impact on airborne particle, fiber, and bioaerosol concentrations...

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.

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.

Acute pyelonephritis in transplanted kidneys: can diffusion-weighted magnetic resonance imaging be useful for diagnosis and follow-up?

PubMed

Faletti, Riccardo; Cassinis, Maria Carla; Gatti, Marco; Giglio, Jacopo; Guarnaccia, Carla; Messina, Marina; Bergamasco, Laura; Fonio, Paolo

2016-03-01

To assess reliability of diffusion-weighted magnetic resonance imaging (DW-MRI) in the management of acute pyelonephritis (APN) foci in transplanted kidneys. In the 2012-2014 period, 24 kidney-transplanted patients underwent MR screening for clinical suspicion of APN. Two readers independently analyzed all images, establishing presence and location of APN foci. The 22 patients who were positive at the MR exam constituted the study population. For each patient the apparent diffusion coefficient (ADC) was measured in the APN foci and in three sites of the healthy parenchyma (case-control comparison). The data were matched to the laboratory measurements for white blood cell, C-reactive protein, and serum creatinine. Forty-six APN foci were found in 22/24 patients. At the acute stage, the difference in ADC between healthy parenchyma and APN foci was significant (2.06 ± 0.16 vs. 1.43 ± 0.32 × 10(-3) mm(2)/s; p < 0.0001). The performance of ADC as APN indicator was tested by the receiving operating characteristics (ROC) curve: the area under curve AUC = 0.99 witnessed an excellent discriminatory ability, with threshold APN/normal parenchyma 1.9 × 10(-3) mm(2)/s. At the 1-month follow-up 43/46 APN foci were no longer visible, with ADC values significantly higher than at the acute stage; all laboratory data were physiological, with WBC significantly reduced from the acute phase (5.2 ± 1.6 × 10(9)/L vs. 10.6 ± 4.8 × 10(9)/L; p < 0.0001). The other 3 patients underwent further therapy and exams, including a third MR. DW-MRI with ADC measurement seems to be a reliable tool in diagnosing and monitoring APN foci in transplanted kidneys, with clinical impact on patient management.

Evaluating Response to High-Dose 13.3 mg/24 h Rivastigmine Patch in Patients with Severe Alzheimer's Disease.

PubMed

Farlow, Martin R; Sadowsky, Carl H; Velting, Drew M; Meng, Xiangyi; Islam, M Zahur

2015-06-01

To identify factors predicting improvement/stabilization on the Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC) and investigate whether early treatment responses can predict long-term outcomes, during a trial of 13.3 mg/24 h versus 4.6 mg/24 h rivastigmine patch in patients with severe Alzheimer's disease (AD). Logistic regression was used to relate Week 24 ADCS-CGIC score to potential baseline predictors. Additional analyses based on receiver-operating characteristic curves were performed using Week 8/16 ADCS-CGIC scores to predict response (13.3 mg/24 h patch) at Week 24. ADCS-CGIC score of (1) 1-3 = "improvement," (2) 1-4 = "improvement or no change". "Treatment" (13.3 mg/24 h patch) and increased age were significant predictors of "improvement" (P = 0.01 and P = 0.003, respectively), and "treatment" (P = 0.001), increased age (P = 0.002), and prior AD treatment (P = 0.03) for "improvement or no change". At Week 8 and 16, ADCS-CGIC scores of 4 and 5 were optimal thresholds in predicting "improvement," and "improvement or no change," respectively, at Week 24. A significant therapeutic effect of high-dose rivastigmine patch on ADCS-CGIC response was observed. The 13.3 mg/24 h patch was identified as a predictor of "improvement" or "improvement or no change". Patients with minimal worsening/improvement/no change after treatment initiation may be more likely to respond following long-term therapy. © 2015 John Wiley & Sons Ltd.

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

PubMed

Bozgeyik, Zulkif; Kocakoc, Ercan; Sonmezgoz, Fitnet

2009-04-01

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

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

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.

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

Multivalent peptidic linker enables identification of preferred sites of conjugation for a potent thialanstatin antibody drug conjugate.

PubMed

Puthenveetil, Sujiet; He, Haiyin; Loganzo, Frank; Musto, Sylvia; Teske, Jesse; Green, Michael; Tan, Xingzhi; Hosselet, Christine; Lucas, Judy; Tumey, L Nathan; Sapra, Puja; Subramanyam, Chakrapani; O'Donnell, Christopher J; Graziani, Edmund I

2017-01-01

Antibody drug conjugates (ADCs) are no longer an unknown entity in the field of cancer therapy with the success of marketed ADCs like ADCETRIS and KADCYLA and numerous others advancing through clinical trials. The pursuit of novel cytotoxic payloads beyond the mictotubule inhibitors and DNA damaging agents has led us to the recent discovery of an mRNA splicing inhibitor, thailanstatin, as a potent ADC payload. In our previous work, we observed that the potency of this payload was uniquely tied to the method of conjugation, with lysine conjugates showing much superior potency as compared to cysteine conjugates. However, the ADC field is rapidly shifting towards site-specific ADCs due to their advantages in manufacturability, characterization and safety. In this work we report the identification of a highly efficacious site-specific thailanstatin ADC. The site of conjugation played a critical role on both the in vitro and in vivo potency of these ADCs. During the course of this study, we developed a novel methodology of loading a single site with multiple payloads using an in situ generated multi-drug carrying peptidic linker that allowed us to rapidly screen for optimal conjugation sites. Using this methodology, we were able to identify a double-cysteine mutant ADC delivering four-loaded thailanstatin that was very efficacious in a gastric cancer xenograft model at 3mg/kg and was also shown to be efficacious against T-DM1 resistant and MDR1 overexpressing tumor cell lines.

The Design of a Single-Bit CMOS Image Sensor for Iris Recognition Applications

PubMed Central

Park, Keunyeol; Song, Minkyu

2018-01-01

This paper presents a single-bit CMOS image sensor (CIS) that uses a data processing technique with an edge detection block for simple iris segmentation. In order to recognize the iris image, the image sensor conventionally captures high-resolution image data in digital code, extracts the iris data, and then compares it with a reference image through a recognition algorithm. However, in this case, the frame rate decreases by the time required for digital signal conversion of multi-bit digital data through the analog-to-digital converter (ADC) in the CIS. In order to reduce the overall processing time as well as the power consumption, we propose a data processing technique with an exclusive OR (XOR) logic gate to obtain single-bit and edge detection image data instead of multi-bit image data through the ADC. In addition, we propose a logarithmic counter to efficiently measure single-bit image data that can be applied to the iris recognition algorithm. The effective area of the proposed single-bit image sensor (174 × 144 pixel) is 2.84 mm2 with a 0.18 μm 1-poly 4-metal CMOS image sensor process. The power consumption of the proposed single-bit CIS is 2.8 mW with a 3.3 V of supply voltage and 520 frame/s of the maximum frame rates. The error rate of the ADC is 0.24 least significant bit (LSB) on an 8-bit ADC basis at a 50 MHz sampling frequency. PMID:29495273

Feasibility of partial replacement of fishmeal with proteins from different sources in diets of Korean rockfish ( Sebastes schlegeli)

NASA Astrophysics Data System (ADS)

Yan, Quangen; Zhu, Xiaoming; Yang, Yunxia; Han, Dong; Xie, Shouqi

2014-12-01

An 8-week feeding experiment was conducted in an indoor recirculation seawater system to investigate the effects of partial replacement of dietary fishmeal with proteins from five sources on the growth performance and feed utilization of Sebastes schlegeli. Six isonitrogenous and isoenergetic diets were formulated using fishmeal (FM, the control) as sole protein source, or proteins from five sources including poultry by-product meal (PBM), meat and bone meal (MBM), soybean meal (SBM), cottonseed meal (CSM) and canola meal (CNM). Fifteen percent of the crude protein provided by fish meal was replaced, respectively. The results showed that the differences in specific growth rate (SGR) and survival rate (SR) among fish fed PBM, MBM, SBM, CSM and whole FM diets were not significant. However, SGR and SR of fish fed CNM diet was significantly lower than that of other treatments. Feeding rate, feed conversion, nutrient retention showed similar patterns to that of growth. Fish fed CSM and CNM showed significantly lower apparent digestibility coefficient (ADC) of dry matter and gross energy than those fed others while fish fed CNM showed lower ADC of crude protein than those fed others ( P<0.05). These results suggested that it was feasible to substitute 15% dietary protein provided by fishmeal with PBM, MBM, SBM and CSM, respectively, but not with CNM as the replacement with CNM reduced fish growth and feed utilization.

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.

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.