Impact of lesion size on reproducibility of quantitative measurement and radiomic features in vessel wall MRI.

OBJECTIVES: To investigate reproducibility of quantitative measurement and radiomic features in vessel wall MRI (VW-MRI), evaluate the impact of lesion size, and identify reproducible radiomic features. METHODS: This retrospective, single-center study included 251 patients (mean age, 53 ± 12 years; 128 women) with atherosclerosis, dissection, aneurysm, moyamoya disease, and vasculitis of the intracranial arteries who underwent three-dimensional turbo spin echo T1-weighted image. Lesion thickness, volume, and signal intensity were measured, and 157 radiomic features were extracted. Intra-observer reproducibility of quantitative measurement and radiomic features was evaluated by calculating the concordance correlation coefficient (CCC) and proportion of radiomic features above the predefined CCC. The reproducibility of quantitative measurement and radiomic features according to lesion size (binary comparison and stratification into 5 and 18 groups) was evaluated. RESULTS: There was an overall serial increase in CCC for thickness measurement when stratified by lesion thickness and volume. There was an overall serial increase in the median CCC for radiomic features and proportion of radiomic features with CCC > 0.85 when stratified by lesion thickness and volume. Reproducibility of radiomic features was higher in the lesions with thickness ≥ 2.5 mm (median CCC, 0.97 vs. 0.89, p < .001; proportion with CCC > 0.85, 88.5% vs. 59.6%, p < .001) and volume ≥ 50 mm3 (median CCC, 0.97 vs. 0.88, p < .001; proportion with CCC > 0.85, 90.4% vs. 59.0%, p < .001). Intensity-based statistical features remained most reproducible in the thinnest and smallest lesions. CONCLUSIONS: Intra-observer reproducibility of thickness measurement and radiomic features was affected by lesion size in VW-MRI although intensity-based statistical features remained most reproducible. KEY POINTS: • There was an overall serial increase in CCC for thickness measurement when stratified by lesion size. • There was an overall serial increase in the median CCC for radiomic features and proportion of radiomic features with CCC > 0.85 when stratified by lesion size. • Intensity-based statistical features remained most reproducible in the thinnest and smallest lesions.

Radiomics-based prediction model for outcomes of PD-1/PD-L1 immunotherapy in metastatic urothelial carcinoma.

OBJECTIVES: To evaluate the usefulness of a radiomics-based prediction model for predicting response and survival outcomes of patients with metastatic urothelial carcinoma treated with immunotherapy targeting programmed cell death 1 (PD-1) and its ligand (PD-L1). METHODS: Sixty-two patients who underwent immunotherapy were divided into training (n = 41) and validation sets (n = 21). A total of 224 measurable lesions were identified on contrast-enhanced CT. A radiomics signature was constructed with features selected using a least absolute shrinkage and selection operator algorithm in the training set. A radiomics-based model was built based on a radiomics signature consisting of five reliable RFs and the presence of visceral organ involvement using multivariate logistic regression. According to a cutoff determined on the training set, patients in the validation set were assigned to either high- or low-risk groups. Kaplan-Meier analysis was performed to compare progression-free and overall survival between high- and low-risk groups. RESULTS: For predicting objective response and disease control, the areas under the receiver operating characteristic curves of the radiomics-based model were 0.87 (95% CI, 0.65-0.97) and 0.88 (95% CI, 0.67-0.98) for the validation set, providing larger net benefit determined by decision curve analysis than without radiomics-based model. The high-risk group in the validation set showed shorter progression-free and overall survival than the low-risk group (log-rank p = 0.044 and p = 0.035). CONCLUSIONS: The radiomics-based model may predict the response and survival outcome in patients treated with PD-1/PD-L1 immunotherapy for metastatic urothelial carcinoma. This approach may provide important and decision tool for planning immunotherapy. KEY POINTS: • A radiomics-based model was built based on radiomics features and the presence of visceral organ involvement for prediction of outcomes in metastatic urothelial carcinoma treated with immunotherapy. • This prediction model demonstrated good prediction of treatment response and higher net benefit than no model in the independent validation set. • This radiomics-based model demonstrated significant associations with progression-free and overall survival between low-risk and high-risk groups.

Hyperoxia-Induced ΔR1.

Background and Purpose- Acceleration of longitudinal relaxation under hyperoxic challenge (ie, hyperoxia-induced ΔR1) indicates oxygen accumulation and reflects baseline tissue oxygenation. We evaluated the feasibility of hyperoxia-induced ΔR1 for evaluating cerebral oxygenation status and degree of ischemic damage in stroke. Methods- In 24-hour transient stroke rat models (n=13), hyperoxia-induced ΔR1, ischemic severity (apparent diffusion coefficient [ADC]), vasogenic edema (R2), total and microvascular blood volume (superparamagnetic iron oxide-driven ΔR2* and ΔR2, respectively), and glucose metabolism activity (18F-fluorodeoxyglucose uptake on positron emission tomography) were measured. The distribution of these parameters according to hyperoxia-induced ΔR1 was analyzed. The partial pressure of tissue oxygen change during hyperoxic challenge was measured using fiberoptic tissue oximetry. In 4-hour stroke models (n=6), ADC and hyperoxia-induced ΔR1 was analyzed with 2,3,5-triphenyltetrazolium chloride staining being a criterion of infarction. Results- Ischemic hemisphere showed significantly higher hyperoxia-induced ΔR1 than nonischemic brain in a pattern depending on ADC. During hyperoxic challenge, ischemic hemisphere demonstrated uncontrolled increase of partial pressure of tissue oxygen, whereas contralateral hemisphere rapidly plateaued. Ischemic hemisphere also demonstrated significant correlation between hyperoxia-induced ΔR1 and R2. Hyperoxia-induced ΔR1 showed a significant negative correlation with 18F-fluorodeoxyglucose uptake. The ADC, R2, ΔR2, and 18F-fluorodeoxyglucose uptake showed a dichotomized distribution according to the hyperoxia-induced ΔR1 as their slopes and values were higher at low hyperoxia-induced ΔR1 (<50 ms-1) than at high ΔR1. In 4-hour stroke rats, the distribution of ADC according to the hyperoxia-induced ΔR1 was similar with 24-hour stroke rats. The hyperoxia-induced ΔR1 was greater in the infarct area (47±10 ms-1) than in peri-infarct area (16±4 ms-1; P<0.01). Conclusions- Hyperoxia-induced ΔR1 adequately indicates cerebral oxygenation and can be a feasible biomarker to classify the degree of ischemia-induced damage in neurovascular function and metabolism in stroke brain.

Prostate cancer detection on dynamic contrast-enhanced MRI: computer-aided diagnosis versus single perfusion parameter maps.

OBJECTIVE: The purpose of this article is to assess the value of computer-aided diagnosis (CAD) for prostate cancer detection on dynamic contrast-enhanced MRI (DCE-MRI). MATERIALS AND METHODS: DCE-MRI examinations of 42 patients with prostate cancer were used to generate perfusion parameters, including baseline and peak signal intensities, initial slope, maximum slope within the initial 50 seconds after the contrast injection (slope(50)), wash-in rate, washout rate, time to peak, percentage of relative enhancement, percentage enhancement ratio, time of arrival, efflux rate constant from the extravascular extracellular space to the blood plasma (k(ep)), first-order rate constant for eliminating gadopentetate dimeglumine from the blood plasma (k(el)), and constant depending on the properties of the tissue and represented by the size of the extravascular extracellular space (A(H)). CAD for cancer detection was established by comprehensive evaluation of parameters using a support vector machine. The diagnostic accuracy of single perfusion parameters was estimated using receiver operating characteristic analysis, which determined threshold and parametric maps for cancer detection. The diagnostic performance of CAD for cancer detection was compared with those of T2-weighted imaging (T2WI) and single perfusion parameter maps, using histologic results as the reference standard. RESULTS: The accuracy, sensitivity, and specificity of CAD were 83%, 77%, and 77%, respectively, in the entire prostate; 77%, 91%, and 64%, respectively, in the transitional zone; and 89%, 89%, and 89%, respectively, in the peripheral zone. Values for k(ep), k(el), initial slope, slope(50), wash-in rate, washout rate, and time to peak showed greater area under the curve values (0.803-0.888) than did the other parameters (0.545-0.665) (p < 0.01) and were compared with values for CAD. In the entire prostate, accuracy was greater for CAD than for all perfusion parameters or T2WI (63-77%); sensitivity was greater for CAD than for T2WI, initial slope, wash-in rate, slope(50), and washout rate (38-77%); and specificity was greater for CAD than for T2WI, k(ep), k(el), and time to peak (59-68%) (p < 0.05). CONCLUSION: CAD can improve the diagnostic performance of DCE-MRI in prostate cancer detection, which may vary according to zonal anatomy.

Diagnosis of lymph node metastasis in uterine cervical cancer: usefulness of computer-aided diagnosis with comprehensive evaluation of MR images and clinical findings.

BACKGROUND: Lymph node (LN) status is an important parameter for determining the treatment strategy and for predicting the prognosis for patients with uterine cervical cancer. Computer-aided diagnosis (CAD) can be feasible for differentiating metastatic from non-metastatic lymph nodes in patients with uterine cervical cancer. PURPOSE: To determine the usefulness of CAD that comprehensively evaluates MR images and clinical findings for detecting LN metastasis in uterine cervical cancer. MATERIAL AND METHODS: In 680 LNs from 143 patients who underwent radical hysterectomy for uterine cervical cancer, the CAD system using the Bayesian classifier estimated the probability of metastasis based on MR findings and clinical findings. We compared the diagnostic accuracy for detecting metastatic LNs in the CAD and MR findings. RESULTS: Metastasis was diagnosed in 70 (12%) LNs from 34 (24%) patients. The area under ROC curves of CAD (0.924) was greater than those of the mean ADC (0.854), minimum ADC (0.849), maximum ADC (0.827), short-axis diameter (0.856) and long-axis diameter (0.753) (P < 0.05). The specificity and accuracy of the CAD (86%, 86%) were greater than those of the mean ADC (77%, 77%), maximum ADC (77%, 77%), minimum ADC (68%, 70%), and short-axis diameter (65%, 67%) (P < 0.05). CONCLUSION: CAD system can improve the diagnostic performance of MR for detecting metastatic LNs in uterine cervical cancer.

Feasibility of FAIR imaging for evaluating tumor perfusion.

PURPOSE: To evaluate the feasibility of flow-sensitive alternating inversion recovery (FAIR) for measuring blood flow in tumor models. MATERIALS AND METHODS: In eight mice tumor models, FAIR and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) was performed. The reliability for measuring blood flow on FAIR was evaluated using the coefficient of variation of blood flow on psoas muscle. Three regions of interest (ROIs) were drawn in the peripheral, intermediate, and central portions within each tumor. The location of ROI was the same on FAIR and DCE-MR images. The correlation between the blood flow on FAIR and perfusion-related parameters on DCE-MRI was evaluated using the Pearson correlation coefficient. RESULTS: The coefficient of variation for measuring blood flow was 9.8%. Blood flow on FAIR showed a strong correlation with Kep (r = 0.77), percent relative enhancement (r = 0.73), and percent enhancement ratio (r = 0.81). The mean values of blood flow (mL/100 g/min) (358 vs. 207), Kep (sec(-) (1)) (7.46 vs. 1.31), percent relative enhancement (179% vs. 134%), and percent enhancement ratio (42% vs. 26%) were greater in the peripheral portion than in the central portion (P < 0.01). CONCLUSION: As blood flow measurement on FAIR is reliable and closely related with that on DCE-MR, FAIR is feasible for measuring tumor blood flow.

Slope of emphysema index: an objective descriptor of regional heterogeneity of emphysema and an independent determinant of pulmonary function.

OBJECTIVE: The purpose of this study was to compare quantitative and visual assessments of regional heterogeneity of emphysema and to investigate the influence of regional heterogeneity on pulmonary function in smoking-related emphysema. MATERIALS AND METHODS: We developed an automatic computerized algorithm to quantitatively assess heterogeneity in the upper-lower, anterior-posterior, and central-peripheral directions. The emphysema index was plotted with a linear function (emphysema index slopes: slope of emphysema index in upper-lower direction, slope of emphysema index in anterior-posterior direction, and slope of emphysema index in central-peripheral direction) for consecutive 1-pixel-thick slices using volumetric CT data of 59 patients (58 men and one woman; mean age, 65.7 years). Emphysema index was defined as the percentage area of lung with attenuation values below -950 HU. Visual assessment was performed using a 5-point scoring system. Quantitative and visual assessments were compared. Multiple linear regression was performed to evaluate the influence of emphysema index and emphysema index slopes on the pulmonary function test. RESULTS: Quantitative and visual assessments were significantly correlated in both upper-lower (r(2) = 0.40 and r(2) = 0.67 for observers 1 and 2, respectively) and central-peripheral (r(2) = 0.51 and r(2) = 0.47, respectively) directions. Multiple linear regression revealed that emphysema index, slope of emphysema index in upper-lower direction, and slope of emphysema index in anterior-posterior direction were independent determinants of forced expiratory volume in 1 second (FEV(1)) (r(2) = 0.30; p < 0.001). Emphysema index and slope of emphysema index in upper-lower direction were independent determinants of the ratio of FEV(1) to forced vital capacity (FEV(1)/FVC) (r(2) = 0.32; p < 0.001). In addition to higher emphysema index, lower and posterior lung dominance was associated with a decrease in FEV(1) and FEV(1)/FVC. CONCLUSION: Computerized, quantitative assessment using the emphysema index slope is comparable to visual assessment in the evaluation of regional heterogeneity of emphysema. In addition to the emphysema index, regional heterogeneity of smoking-related emphysema contributes to impairment of pulmonary function.

Reliability of CT radiomic features reflecting tumour heterogeneity according to image quality and image processing parameters.

The reliability of radiomics features (RFs) is crucial for quantifying tumour heterogeneity. We assessed the influence of imaging, segmentation, and processing conditions (quantization range, bin number, signal-to-noise ratio [SNR], and unintended outliers) on RF measurement. Low SNR and unintended outliers increased the standard deviation and mean values of histograms to calculate the first-order RFs. Variations in imaging processing conditions significantly altered the shape of the probability distribution (centre of distribution, extent of dispersion, and segmentation of probability clusters) in second-order RF matrices (i.e. grey-level co-occurrence and grey-level run length), thereby eventually causing fluctuations in RF estimation. Inconsistent imaging and processing conditions decreased the number of reliably measured RFs in terms of individual RF values (intraclass correlation coefficient ≥0.75) and inter-lesion RF ratios (coefficient of variation <15%). No RF could be reliably estimated under inconsistent SNR and inclusion of outlier conditions. By contrast, with high SNR and no outliers, all first-order RFs, 11 (42%) grey-level co-occurrence RFs and five (42%) grey-level run length RFs showed acceptable reliability. Our study suggests that optimization of SNR, exclusion of outliers, and application of relevant quantization range and bin number should be performed to ensure the robustness of radiomics studies assessing tumor heterogeneity.

Node-by-node correlation between MR and PET/CT in patients with uterine cervical cancer: diffusion-weighted imaging versus size-based criteria on T2WI.

The purpose of the study was to perform a node-by-node comparison of an ADC-based diagnosis and various size-based criteria on T2-weighted imaging (T2WI) with regard to their correlation with PET/CT findings in patients with uterine cervical cancer. In 163 patients with 339 pelvic lymph nodes (LNs) with short-axis diameter >5 mm, the minimum apparent diffusion coefficient (ADC), mean ADC, short- and long-axis diameters, and ratio of long- to short-axis diameters (L/S ratio) were compared in PET/CT-positive and -negative LNs. On PET/CT, 118 (35%) LNs in 58 patients were positive. The mean value of minimum and mean ADCs, short- and long-axis diameters, and L/S ratio were different in PET/CT-positive (0.6436 x 10(-3) mm(2)/s, 0.756 x 10(-3) mm(2)/s, 10.3 mm, 13.2 mm, 1.32, respectively) and PET/CT-negative LNs (0.8893 x 10(-3) mm(2)/s, 1.019 x 10(-3) mm(2)/s, 7.4 mm, 11.0 mm, 1.49, respectively) (P < 0.05). The Az value of the minimum ADC (0.864) was greater than those of mean ADC (0.836), short-axis diameter (0.764), long-axis diameter (0.640) and L/S ratio (0.652) (P < 0.05). The sensitivity and accuracy of the minimum ADC (86%, 82%) were greater than those of the short-axis diameter (55%, 74%), long-axis diameter (73%, 58%) and L/S ratio (52%, 66%) (P < 0.05). ADC showed superior correlation with PET/CT compared with conventional size-based criteria on T2WI.

Spatiotemporal heterogeneity of tumor vasculature during tumor growth and antiangiogenic treatment: MRI assessment using permeability and blood volume parameters.

Tumor heterogeneity is an important concept when assessing intratumoral variety in vascular phenotypes and responses to antiangiogenic treatment. This study explored spatiotemporal heterogeneity of vascular alterations in C6 glioma mice during tumor growth and antiangiogenic treatment on serial MR examinations (days 0, 4, and 7 from initiation of vehicle or multireceptor tyrosine kinase inhibitor administration). Transvascular permeability (TP) was quantified on dynamic-contrast-enhanced MRI (DCE-MRI) using extravascular extracellular agent (Gd-DOTA); blood volume (BV) was estimated using intravascular T2 agent (SPION). With regard to region-dependent variability in vascular phenotypes, the control group demonstrated higher TP in the tumor center than in the periphery, and greater BV in the tumor periphery than in the center. This distribution pattern became more apparent with tumor growth. Antiangiogenic treatment effect was regionally heterogeneous: in the tumor center, treatment significantly suppressed the increase in TP and decrease in BV (ie, typical temporal change in the control group); in the tumor periphery, treatment-induced vascular alterations were insignificant and BV remained high. On histopathological examination, the control group showed greater CD31, VEGFR2, Ki67, and NG2 expression in the tumor periphery than in the center. After treatment, CD31 and Ki67 expression was significantly suppressed only in the tumor center, whereas VEGFR2 and α-caspase 3 expression was decreased and NG2 expression was increased in the entire tumor. These results demonstrate that MRI can reliably depict spatial heterogeneity in tumor vascular phenotypes and antiangiogenic treatment effects. Preserved angiogenic activity (high BV on MRI and high CD31) and proliferation (high Ki67) in the tumor periphery after treatment may provide insights into the mechanism of tumor resistance to antiangiogenic treatment.

Structure-activity relationship studies of a series of novel delta-lactam-based histone deacetylase inhibitors.

We synthesized a series of delta-lactam-based HDAC inhibitors that were identified with various degrees of anti-inflammatory and cell growth inhibitory activities. Compounds possessing significant HDAC inhibitory activity exhibited both anti-inflammatory and cell growth inhibitory activities as well as significant tumor growth inhibition in the in vivo tumor xenograft experiments. Besides, these compounds demonstrated anti-inflammatory properties in vitro via suppression of the production of the proinflammatory cytokine TNF-alpha and nitric oxide by LPS-stimulated RAW264.7 cells.

Multichannel transceiver dual-tuned RF coil for proton/sodium MR imaging of knee cartilage at 3 T.

Sodium magnetic resonance (MR) imaging is a promising technique for detecting changes of proteoglycan (PG) content in cartilage associated with knee osteoarthritis. Despite its potential clinical benefit, sodium MR imaging in vivo is challenging because of intrinsically low sodium concentration and low MR signal sensitivity. Some of the challenges in sodium MR imaging may be eliminated by the use of a high-sensitivity radiofrequency (RF) coil, specifically, a dual-tuned (DT) proton/sodium RF coil which facilitates the co-registration of sodium and proton MR images and the evaluation of both physiochemical and structural properties of knee cartilage. Nevertheless, implementation of a DT proton/sodium RF coil is technically difficult because of the coupling effect between the coil elements (particularly at high field) and the required compact design with improved coil sensitivity. In this study, we applied a multitransceiver RF coil design to develop a DT proton/sodium coil for knee cartilage imaging at 3 T. With the new design, the size of the coil was minimized, and a high signal-to-noise ratio (SNR) was achieved. DT coil exhibited high levels of reflection S11 (∼-21 dB) and transmission coefficient S12 (∼-19 dB) for both the proton and sodium coils. High SNR (range 27-38) and contrast-to-noise ratio (CNR) (range 15-21) were achieved in sodium MR imaging of knee cartilage in vivo at 3-mm(3) isotropic resolution. This DT coil performance was comparable to that measured using a sodium-only birdcage coil (SNR of 28 and CNR of 20). Clinical evaluation of the DT coil on four normal subjects demonstrated a consistent acquisition of high-resolution proton images and measurement of relative sodium concentrations of knee cartilages without repositioning of the subjects during the same MR scanning session.

Relative apparent diffusion coefficient: determination of reference site and validation of benefit for detecting metastatic lymph nodes in uterine cervical cancer.

PURPOSE: To determine the reference site for relative apparent diffusion coefficient (rADC) and to evaluate the benefit of rADC for detecting metastatic lymph nodes in uterine cervical cancer. MATERIALS AND METHODS: Two observers independently measured ADCs in the spleen, liver, renal cortex, lumbar spine, lumbar spinal cord, and gluteus maximus on diffusion-weighted images (b value, 0 and 1000 mm/sec(2)) in 50 patients. The reference site for rADC was determined using the intra- and interobserver coefficient of variation (CV) of ADC in these organs. rADC was calculated by ADC(lesion)/ADC(reference site). The benefit of rADC over ADC was validated by comparing the area under the receiver operating curve for identifying metastatic lymph nodes in uterine cervical cancer in 130 patients. RESULTS: The renal cortex was determined to be the reference site for rADC, as its CVs (intraobserver, 5%-7%; interobserver, 5%) were less than those of the other organs (P < 0.05). The ADC and rADC of metastatic lymph nodes (n = 29, ADC, 0.7483 x 10(-3) mm(2)/sec; rADC, 0.3832) were less than those of nonmetastatic lymph nodes (n = 229, ADC, 0.9960 x 10(-3) mm(2)/sec; rADC, 0.5383) (P < 0.05). The area under the receiver operating characteristics curve for differentiating metastatic from nonmetastatic lymph nodes was greater for rADC (0.914; 95% confidence interval [CI], 0.872-0.945) than for ADC (0.872; 95% CI, 0.825-0.910) (P = 0.007). CONCLUSION: The renal cortex is an appropriate reference site for rADC and rADC may improve the accuracy for diagnosing metastatic lymph nodes in uterine cervical cancer.

Feasibility of automated quantification of regional disease patterns depicted on high-resolution computed tomography in patients with various diffuse lung diseases.

OBJECTIVE: This study was designed to develop an automated system for quantification of various regional disease patterns of diffuse lung diseases as depicted on high-resolution computed tomography (HRCT) and to compare the performance of the automated system with human readers. MATERIALS AND METHODS: A total of 600 circular regions-of-interest (ROIs), 10 pixels in diameter, were utilized. The 600 ROIs comprised 100 ROIs that represented six typical regional patterns (normal, ground-glass opacity, reticular opacity, honeycombing, emphysema, and consolidation). The ROIs were used to train the automated classification system based on the use of a Support Vector Machine classifier and 37 features of texture and shape. The performance of the classification system was tested with a 5-fold cross-validation method. An automated quantification system was developed with a moving ROI in the lung area, which helped classify each pixel into six categories. A total of 92 HRCT images obtained from patients with different diseases were used to validate the quantification system. Two radiologists independently classified lung areas of the same CT images into six patterns using the manual drawing function of dedicated software. Agreement between the automated system and the readers and between the two individual readers was assessed. RESULTS: The overall accuracy of the system to classify each disease pattern based on the typical ROIs was 89%. When the quantification results were examined, the average agreement between the system and each radiologist was 52% and 49%, respectively. The agreement between the two radiologists was 67%. CONCLUSION: An automated quantification system for various regional patterns of diffuse interstitial lung diseases can be used for objective and reproducible assessment of disease severity.

Apparent diffusion coefficient: prostate cancer versus noncancerous tissue according to anatomical region.

PURPOSE: To evaluate diagnostic performance of apparent diffusion coefficient (ADC) in differentiating prostate cancer from noncancerous tissue according to anatomical region. MATERIALS AND METHODS: In 47 patients with diffusion-weighted-MR (b-value, 0 and 1000 sec/mm2) on a 1.5 T unit, ADCs were measured in prostate cancer and in three noncancerous tissues (transitional zone, peripheral zone, and prostatic base). Diagnostic performance of ADC for differentiating cancer from noncancerous tissue was evaluated using receiver-operating-characteristics (ROC) analysis. RESULTS: Mean ADC of prostate cancer (0.963x10(-3) mm2/s) was lower than those of all noncancerous tissues (P<0.001). In noncancerous tissue, ADC differed according to anatomical region (peripheral zone, 1.572x10(-3) mm2/sec; transitional zone, 1.441x10(-3) mm2/sec; prostatic base, 1.146x10(-3) mm2/sec) (P<0.01). ADC was lower in prostate cancer than in all noncancerous tissues in 34 (72%) patients. Area under the ROC curve for differentiating cancer from noncancerous tissue in prostatic base (0.725) was less than those for differentiating cancer from noncancerous tissue in peripheral (0.952) and transitional zones (0.906) (P<0.05). Sensitivity differed according to anatomical region (peripheral zone, 98%; transitional zone, 82%; prostatic base, 66%) (P<0.05). CONCLUSION: Variable ADC in noncancerous tissue according to anatomical region may limit diagnostic performance of ADC for cancer detection.

Feasibility of diffusion-weighted imaging in the differentiation of metastatic from nonmetastatic lymph nodes: early experience.

PURPOSE: To investigate the feasibility of diffusion-weighted imaging (DWI) in the differentiation of metastatic from nonmetastatic lymph nodes. MATERIALS AND METHODS: In 125 patients who underwent lymph node dissection for uterine cervical cancer, DWI was performed at b value of 0 and 1000 s/mm2. By referring to the surgical maps of the pelvic lymph nodes, the apparent diffusion coefficient (ADC) was compared in the metastatic and nonmetastatic lymph nodes, and receiver-operating-characteristics analysis was performed to evaluate the diagnostic performance of the ADC in differentiating metastatic from nonmetastatic lymph nodes. RESULTS: The ADC were significantly lower in the metastatic lymph nodes (0.7651x10(-3) mm2/s+/-0.1137) than in the nonmetastatic lymph nodes (1.0021x10(-3) mm2/s+/-0.1859; P<0.001). The area-under-the-curve of ADC for differentiating metastatic from nonmetastatic lymph nodes, was 0.902. The sensitivity and specificity of ADC for differentiating metastatic from nonmetastatic lymph nodes, were 87% for the ADC and 80%, respectively. CONCLUSION: DWI is feasible for differentiating metastatic from nonmetastatic lymph nodes in patients with uterine cervical cancer.

Synthesis, enzymatic inhibition, and cancer cell growth inhibition of novel delta-lactam-based histone deacetylase (HDAC) inhibitors.

delta-Lactam-based hydroxamic acids, inhibitors of histone deacetylase (HDAC), have been synthesized via ring closure metathesis of key diene intermediates followed by conversion to hydroxamic acid analogues. The hydroxamic acids 12a, 12b, and 17c showed potent inhibitory activity in HDAC enzyme assay. The hydroxamic acid 12b exhibited growth inhibitory activity on five human tumor cell lines, showing good sensitivity on the MDA-MB-231 breast tumor cell.