Focal nodular enhancement on DCE MRI of the prostatectomy bed: radiologic-pathologic correlations and prognostic value.

OBJECTIVES: To determine the concordance of dynamic contrast-enhanced (DCE) imaging findings with clinico-pathologic characteristics and their prognostic impact for predicting biochemical recurrence (BCR) in patients who underwent radical prostatectomy (RP) for prostate cancer. METHODS: This retrospective study included patients who underwent MRI within 1 year after RP between November 2019 and October 2020. DCE findings and their concordance with the presence and location of positive surgical margin (PSM) were assessed using RP specimens. Kaplan-Meier and logistic regression analyses were used to evaluate the prognostic impact of DCE findings for BCR. RESULTS: Among the 272 men (mean age ± standard deviation, 66.6 ± 7.4 years), focal nodular enhancement was more frequently observed in those with PSM compared to those with negative margin (85.4% versus 14.6%; p < 0.001). The sites of focal nodular enhancement were 72.9% (35/48) concordant with the PSM locations. Focal nodular enhancement was associated with a higher Gleason score, higher preoperative PSA (≥ 10 ng/mL), higher Gleason grade at the surgical margin, and non-limited margin involvement (p = 0.002, 0.006, 0.032, and 0.001, respectively). In patients without BCR at the time of MRI, focal nodular enhancement was associated with a shorter time to BCR (p < 0.001) and a significant factor predicting 1-year BCR in both univariate (odds ratio = 8.4 [95% CI: 2.5-28.3]; p = 0.001) and multivariate (odds ratio = 5.49 [1.56-19.3]; p = 0.008) analyses. CONCLUSIONS: Focal nodular enhancement on post-prostatectomy MRI was associated with adverse clinico-pathologic characteristics of high risk for recurrence and can be a predictor for 1-year BCR in patients undergoing RP. KEY POINTS: • Focal nodular enhancement (PI-RR DCE score ≥ 4) was 72.9% (35/48) concordant with the site of positive resection margin by radiologic-histologic correlation. • Focal nodular enhancement (PI-RR DCE score ≥ 4) was associated with higher Gleason score ( ≥ 8), preoperative PSA ( > 10 ng/mL), and Gleason grade 4 or 5 at the surgical margin and non-limited margin involvement (p ≤ 0.032). • In patients without BCR at the time of MRI, focal nodular enhancement was a significant factor predicting 1-year BCR (odds ratio = 5.49; 95% CI: 1.56-19.3; p = 0.008).

Fast T2-Weighted Imaging With Deep Learning-Based Reconstruction: Evaluation of Image Quality and Diagnostic Performance in Patients Undergoing Radical Prostatectomy.

BACKGROUND: Deep learning-based reconstruction (DLR) can potentially improve image quality by reduction of noise, thereby enabling fast acquisition of magnetic resonance imaging (MRI). However, a systematic evaluation of image quality and diagnostic performance of MRI using short acquisition time with DLR has rarely been investigated in men with prostate cancer. PURPOSE: To assess the image quality and diagnostic performance of MRI using short acquisition time with DLR for the evaluation of extraprostatic extension (EPE). STUDY TYPE: Retrospective. POPULATION: One hundred and nine men. FIELD STRENGTH/SEQUENCE: 3 T; turbo spin echo T2-weighted images (T2WI), echo-planar diffusion-weighted, and spoiled gradient echo dynamic contrast-enhanced images. ASSESSMENT: To compare image quality, signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) and subjective analysis using Likert scales on three T2WIs (MRI using conventional acquisition time, MRI using short acquisition time [fast MRI], and fast MRI with DLR) were performed. The diagnostic performance for EPE was evaluated by three independent readers. STATISTICAL TESTS: SNR, CNR, and image quality scores across the three imaging protocols were compared using Friedman tests. The diagnostic performance for EPE was assessed using the area under receiver operating characteristic curves (AUCs). P < 0.05 was considered statistically significant. RESULTS: Fast MRI with DLR demonstrated significantly higher SNR (mean ± SD, 14.7 ± 6.8 vs. 8.8 ± 4.9) and CNR (mean ± SD, 6.5 ± 6.3 vs. 3.4 ± 3.6) values and higher image quality scores (median, 4.0 vs. 3.0 for three readers) than fast MRI. The AUCs for EPE were significantly higher with the use of DLR (0.86 vs. 0.75 for reader 2 and 0.82 vs. 0.73 for reader 3) compared with fast MRI, whereas differences were not significant for reader 1 (0.81 vs. 0.74; P = 0.09). DATA CONCLUSION: DLR may be useful in reducing the acquisition time of prostate MRI without compromising image quality or diagnostic performance. LEVEL OF EVIDENCE: 4 TECHNICAL EFFICACY: Stage 3.

Amide Proton Transfer-weighted 7-T MRI Contrast of Myelination after Cuprizone Administration.

Background Investigations of amide proton signal changes in the white matter of demyelinating diseases may provide important biophysical information for diagnostic and prognostic assessments. Purpose To evaluate amide proton signals in cuprizone-induced rats using amide proton transfer-weighted (APTw) MRI, which provides in vivo image contrast by changing amide proton concentrations during demyelination (DEM) and subsequent remyelination (REM). Materials and Methods In this animal study, APTw 7-T MRI was performed in 21 male Wistar rats divided into cuprizone-induced (n = 14) and control (n = 7) groups from February to August 2020. The cuprizone-induced group was further subdivided into DEM (n = 7) and REM (n = 7) groups. Seven weeks after cuprizone feeding, rats in the DEM group were killed prior to transmission electron microscopy and myelin staining, while rats in the REM group were changed to a normal chow diet and fed for 5 weeks. In each group, the APTw signals were calculated using a conventional magnetization transfer ratio at 3.5 ppm based on regions of interest in the corpus callosum. Statistical differences in APTw signals among the groups were analyzed with one-way analysis of variance followed by Tukey post hoc tests. Results The mean APTw signals in the control and DEM groups were -4.42% ± 0.60 (standard deviation) (95% CI: -4.98, -3.86) and -2.57% ± 0.48 (95% CI: -3.01, -2.12), respectively, indicating higher in vivo APTw signals in the DEM lesion (P < .001). After REM, mean APTw signal in the REM group was -3.83% ± 0.67 (95% CI: -4.45, -3.22), similar to that in the control group (P = .18) and lower than that in the DEM group (P < .001). Conclusion Significant amide proton transfer-weighted (APTw) metric changes coupled with the histologic characteristics of the demyelination and remyelination processes indicate the potential usefulness of APTw 7-T MRI to monitor earlier myelination processes. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by van Zijl in this issue.

Treatment of chemotherapy-induced cachexia with BST204: a multimodal validation study.

INTRODUCTION: Chemotherapy is a major etiology of cachexia. Ginseng products are known to have various anti-cachectic and health-promoting effects, such as inhibiting inflammation and promoting energy production. In particular, BST204, purified ginseng dry extract, contains multiple ginsenosides that can reduce chemotherapy-related fatigue and toxicity. OBJECTIVES: To investigate the effects of BST204 on the alleviation of chemotherapy-induced cachexia using a multimodal approach. METHODS: In a CT26 mouse syngeneic colon cancer model, cachexia was predominantly induced by chemotherapy with 5-fluorouracil (5-FU) than by tumor growth. BST204 at a dose of 100 or 200 mg/kg was administered to 5-FU-treated mice. RESULTS: BST204 significantly mitigated the decrease in tumor-excluded body weight (change in 5-FU group and BST204 groups: - 13% vs. - 6% on day 7; - 30% vs. - 20% on day 11), muscle volume (- 19% vs. - 11%), and fat volume (- 91% vs. - 56%). The anti-cachectic effect of BST204 was histologically demonstrated by an improved balance between muscle regeneration and degeneration and a decrease in muscle cross-sectional area reduction. CONCLUSION: Chemotherapy-induced cachexia was biochemically and metabolically characterized by activated inflammation, enhanced oxidative stress, increased protein degradation, decreased protein stabilization, reduced glucose-mediated energy production, and deactivated glucose-mediated biosynthesis. These adverse effects were significantly improved by BST204 treatment. Overall, our multimodal study demonstrated that BST204 could effectively alleviate chemotherapy-induced cachexia.

Ancillary imaging and clinical features for the characterization of prostate lesions: A proposed approach to reduce false positives.

The relatively low specificity and positive predictive value of the Prostate Imaging-Reporting and Data System (PI-RADS) can lead to considerable false-positive results and unnecessary biopsies. The aim of this study was to propose ancillary features (AFs) indicating clinically significant prostate cancer (csPCa) or benign tissues in PI-RADS category ≥3 lesions and determine the usefulness of these AFs in reducing false-positive assessments of suspicious lesions in men at csPCa risk. This was a retrospective study, which included 199 men. A 3T, including turbo spin echo T2 -weighted, echo-planar diffusion-weighted, and spoiled gradient echo dynamic contrast-enhanced (DCE) images, was used. Five AFs (prostate-specific antigen density ≥0.15 ng/mL2 ; size ≥10 mm; heterogeneous T2 signal intensity; circumscribed nodule in the junction of peripheral and transition zone; and DCE time curves) indicating csPCa or non-csPCa were evaluated by three independent readers. The sensitivity and specificity of each AF were calculated. Inter-reader agreement was evaluated using κ statistics. Univariate and multivariate logistic regression analyses were conducted to determine significant AFs. The reduction in positive call rates and csPCa detection rates with combined AF use were calculated and compared with the findings obtained with PI-RADS use alone. The sensitivities and specificities of the AFs indicating csPCa were 72.1%-96.5% and 27.4%-75.2% for reader 1, 66.3%-96.5% and 23.9%-62.0% for reader 2, and 67.4%-96.5% and 34.5%-78.8% for reader 3, with moderate to substantial inter-reader agreement (Fleiss κ, 0.551-0.643). The combined use of two or more AFs for assessing PI-RADS ≥3 lesions resulted in a 19.6%-30.7% reduction in positive calls (p < .05) compared to PI-RADS use alone while preserving the csPCa detection rates (p ≥ .06) for three readers. The use of AFs in combination with PI-RADS can reduce positive calls and false positives without csPCa under-detection.

Performance of Prostate Imaging Reporting and Data System Version 2.1 for Diagnosis of Prostate Cancer: A Systematic Review and Meta-Analysis.

BACKGROUND: The Prostate Imaging Reporting and Data System (PI-RADS) was introduced in 2012 and updated to version 2.1 (v2.1) in early 2019 to improve diagnostic performance and interreader reliability. PURPOSE: To evaluate the diagnostic performance of PI-RADS v2.1 in comparison with v2. METHODS: A systematic review and meta-analysis of the literature was performed using MEDLINE, EMBASE, and Cochrane databases to identify studies evaluating the diagnostic performance of PI-RADS v2.1 for diagnosing clinically significant prostate cancer (csPCa). STUDY TYPE: Systematic review and meta-analysis. SUBJECT: One thousand two hundred forty-eight patients with 1406 lesions from 10 eligible articles. FIELD STRENGTH/SEQUENCE: Conventional MR sequences at 1.5 T and 3 T. ASSESSMENT: Two reviewers independently identified and reviewed the original articles reporting diagnostic performance of PI-RADS v2.1. STATISTICAL TESTS: Meta-analytic summary sensitivity and specificity were calculated using a bivariate random effects model. Meta-analytic sensitivity and specificity between PI-RADS v2 and v2.1 were compared. RESULTS: The pooled sensitivity and specificity of PI-RADS v2.1 were 87% (95% confidence intervals, 82-91%) and 74% (63-82%), respectively. In five studies available for a head-to-head comparison between PI-RADS v2.1 and v2, there were no significant differences in either sensitivity (90% [86-94%] vs. 88% [83-93%], respectively) or specificity (76% [59-93%] vs. 61% [39-83%], respectively; P = 0.37). The sensitivity and specificity were 81% (73-87%) and 82% (68-91%), respectively, for a PI-RADS score cutoff of ≥4, and 94% (88-97%) and 56% (35-97%) for ≥3. Regarding the zonal location, the sensitivity and specificity for the transitional zone only were 90% (84-96%) and 76% (62-90%) respectively, whereas for the whole gland they were 85% (79-91%) and 71% (57-85%). DATA CONCLUSION: PI-RADS v2.1 demonstrated good overall performance for the diagnosis of csPCa. PI-RADS v2.1 tended to show higher specificity than v2, but the difference lacked statistical significance. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY STAGE: 3.

Preoperative MRI-based estimation of risk for positive resection margin after radical prostatectomy in patients with prostate cancer: development and validation of a simple scoring system.

OBJECTIVES: To develop a simplified MRI-based model to predict the risk for positive surgical margins (PSMs) after radical prostatectomy (RP) in patients with prostate cancer (PCa). METHODS: Consecutive patients who underwent RP for PCa were retrospectively identified from a tertiary referral hospital. Patients who underwent RP between January 2014 and June 2014 were assigned as derivation cohort (n = 330) and those between January 2018 and February 2018 were assigned as validation cohort (n = 100). MRI-based predictors associated with PSM were assessed: tumor size, tumor-capsule contact length, the Prostate Imaging Reporting and Data System (PI-RADS) category, tumor location (tumor contact to the apex or posterolateral side near the neurovascular bundle), apical depth, and prostate volume. A prediction model was developed by using multivariable logistic regression, and then it was transformed into a scoring system. The prediction and calibration performance of this scoring system was evaluated using the C statistics and Hosmer-Lemeshow goodness-of-fit test. RESULTS: A total of 121 (36.7%) and 32 (32.0%) of patients in the derivation and validation cohorts had PSMs after RP. The scoring system consisted of the following variables: tumor-capsule contact length, PI-RADS category, tumor located at the apex and/or posterolateral side. This scoring system provided good prediction performance for PSM in the derivation (C statistics, 0.80 [95% CI: 0.76, 0.85]) and validation (C statistics, 0.77 [95% CI: 0.68, 0.87]) cohorts, and also showed good calibration in both cohorts (p = 0.83 and 0.86, respectively). CONCLUSIONS: An MRI-based scoring system can help estimate the risk of PSM after RP. KEY POINTS: • An MRI-based scoring system served as a tool to estimate the risk of positive surgical margin (C statistics, 0.80 and 0.77 in the derivation and validation cohorts, respectively) after radical prostatectomy. • Tumor with contact to the apex or posterolateral aspect, the tumor contact length to capsule, and higher PI-RADS category were independent predictors for the presence of positive resection margins after radical prostatectomy in men with prostate cancer. • High-risk patients as determined by the scoring system demonstrated adverse post-surgical outcomes compared with low- or intermediate-risk patients, in regard to longer length (mean length, 13.0 mm versus 3.9 mm in low risk or 6.2 mm in intermediate risk; p ≤ 0.001) and higher Gleason grade at the margin (grades 4 and 5 in 69.4% and 20.4% versus 16.7% and 16.7% in low risk or 46.7% and 5.4% in intermediate risk; p < 0.001).

Bosniak Classification of Cystic Renal Masses Version 2019: Comparison With Version 2005 for Class Distribution, Diagnostic Performance, and Interreader Agreement Using CT and MRI.

BACKGROUND. The Bosniak classification system for cystic renal masses (CRMs) was updated in 2019, requiring further investigation. OBJECTIVE. The purpose of this study was to compare versions 2005 and 2019 of the Bosniak classification system in terms of class distribution, diagnostic performance, interreader agreement, and intermodality agreement between CT and MRI. METHODS. This retrospective study included 100 patients (mean age, 52.4 ± 11.6 years; 68 men, 32 women) with 104 CRMs (74 malignant) who underwent CT, MRI, and resection between 2010 and 2019. Two radiologists independently evaluated CRMs in separate sessions for each combination of version and modality and assigned a Bosniak class. Diagnostic performance was compared using McNemar tests. Interreader and intermodality agreement were analyzed using weighted kappa coefficients. RESULTS. Across readers and modalities, the proportion of class IIF CRMs was higher for version 2019 than version 2005 (reader 1: 28.8-30.8% vs 6.7-12.5%; reader 2: 26.0-28.8% vs 8.7-19.2%), although 95% CIs overlapped for reader 2 on CT. The proportion of class III CRMs was lower for version 2019 than version 2005 (reader 1: 33.7-35.6% vs 49.0-51.9%; reader 2: 31.7-40.4% vs 37.5-52.9%), although 95% CIs overlapped for all comparisons. Version 2019 showed lower sensitivity for malignancy than version 2005 across readers and modalities (all p < .05); for example, using CT, sensitivity was 75.7% for both readers with version 2019 versus 85.1-87.8% with version 2005. However, version 2019 showed higher specificity than version 2005, which was significant (all p < .05) for reader 1. For example, using CT, specificity was 73.3% (reader 1) and 70.0% (reader 2) with version 2019 versus 50.0% (reader 1) and 56.7% (reader 2) with version 2005. Diagnostic accuracy was not different between versions (version 2005: 76.9-85.6%; version 2019: 74.0-78.8%). Interreader and intermodality agreement were substantial for version 2005 (κ = 0.676-0.782 and 0.711-0.723, respectively) and version 2019 (κ = 0.756-0.804 and 0.704-0.781, respectively). CONCLUSION. Use of version 2019 versus version 2005 of the Bosniak classification system results in a shift in CRM assignment from class III to class IIF. Version 2019 results in lower sensitivity, higher specificity, and similar accuracy versus version 2005. Interreader and intermodality agreement are similar between versions. CLINICAL IMPACT. Version 2019 facilitates recommending imaging surveillance for more CRMs.

Magnetic Resonance Imaging for Drug Development.

Given the merit of high-resolution cross-sectional imaging, magnetic resonance imaging (MRI) has been utilized in many preclinical and clinical research fields. In addition to T2-weighted imaging for assessing anatomic changes by disease and therapeutic agents, diffusion-weighted imaging, dynamic contrast-enhanced MRI, and MR spectroscopy can provide disease- and drug-specific functional information in both in vivo and ex vivo status. Another advantage of MRI is its ability to bridge the preclinical and clinical experiments as it allows similar study methods and environments between animals and humans. Therefore, MRI can be used as a useful tool for drug development. Investigators have discovered a variety of MRI biomarkers that can quantitatively measure the biological alteration led by disease and treatment. In this chapter, a number of commonly used preclinical MRI biomarkers for drug development will be introduced and discussed, particularly being focused on their value for translational research.

Extraprostatic Tumor Extension: Comparison of Preoperative Multiparametric MRI Criteria and Histopathologic Correlation after Radical Prostatectomy.

Background There are no standardized and well-validated criteria for assessing the risk of extraprostatic extension (EPE) of prostate cancer at preoperative multiparametric MRI. Purpose To compare diagnostic performance, intra- and interreader agreement, and correlations of MRI-based criteria for assessment of EPE after radical prostatectomy, including EPE grade, European Society of Urogenital Radiology (ESUR) score, Likert scale, and capsular contact length (CCL). Materials and Methods This retrospective study included consecutive men who underwent MRI and radical prostatectomy between July 2016 and March 2017. Two genitourinary radiologists independently estimated the probability of EPE by using four MRI-based scoring methods. The diagnostic accuracies and intra- and interobserver agreement were evaluated with area under the receiver operating characteristic curve (AUC) and κ statistics, respectively. Correlations between MRI-based score and histologic extent of EPE were analyzed by using the Spearman correlation coefficient (ρ). Results A total of 301 men (mean age ± standard deviation, 65 years ± 7) were evaluated. A total of 129 (42.9%) men had EPE. The AUC ranges of EPE grade, ESUR score, Likert scale, and CCL for assessment of EPE were 0.77-0.81, 0.79-0.81, 0.78-0.79, and 0.78-0.85, respectively, for the two readers. The Likert scale showed lower sensitivity (68.2% [88 of 129] for reader 1, 72.1% [93 of 129] for reader 2) than did EPE grade (77.5% [100 of 129] for reader 1, 79.8% [103 of 129] for reader 2; P ≤ .04). Intra- and interreader agreement were substantial (κ range, 0.61-0.74) for the four methods, with ESUR score showing the lowest values (κ = 0.61 and κ = 0.63, respectively). EPE grade showed highest correlation with histologic extent of EPE (ρ = 0.53 and ρ = 0.55 for circumferential length; ρ = 0.42 and ρ = 0.55 for radial length for readers 1 and 2, respectively; P < .001). Conclusion Extraprostatic extension (EPE) grade, European Society of Urogenital Radiology score, Likert scale, and capsular contact length showed good overall diagnostic performance; however, the EPE grade resulted in more reliable performance and had the highest correlation with histologic EPE extent. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Padhani and Petralia in this issue.

Interreader Agreement with Prostate Imaging Reporting and Data System Version 2 for Prostate Cancer Detection: A Systematic Review and Meta-Analysis.

PURPOSE: We evaluated interreader agreement with PI-RADS® (Prostate Imaging Reporting and Data System) version 2 for detection of prostate cancer. MATERIALS AND METHODS: We searched MEDLINE®, Embase® and the Cochrane Library between 2015 and June 3, 2019 to identify original research reporting interreader agreement in the use of PI-RADS version 2. Quality of the retrieved studies was assessed by 2 independent reviewers using the Guidelines for Reporting Reliability and Agreement Studies. Pooled κ for PI-RADS version 2 was calculated, and a head-to-head comparison with version 1 was performed for the available studies. Subgroup analysis was performed according to zonal anatomy (peripheral or transitional zone), cutoff value (4 or higher, or 3 or higher) and specific imaging sequences (T2-weighted, diffusion-weighted and dynamic contrast enhanced). Meta-regression analysis was performed to assess the cause of study heterogeneity. RESULTS: A total of 30 studies (4,095 patients) were included. Pooled κ of PI-RADS version 2 was 0.61 (95% CI 0.55-0.67). In 4 studies evaluating head-to-head comparisons PI-RADS versions 1 and 2 showed similar pooled κ values (0.61, 95% CI 0.33-0.90 vs 0.68, 95% CI 0.57-0.79; p=0.61). Substantial interreader agreement was noted with a cutoff of 4 or higher (κ=0.61) and moderate agreement was observed with a cutoff of 3 or higher (κ=0.57), peripheral zone (κ=0.64), transitional zone (κ=0.49) and the 3 magnetic resonance imaging sequences (κ 0.42-0.58). Difference in reader experience was the single significant factor affecting study heterogeneity (p=0.01). CONCLUSIONS: PI-RADS version 2 provides substantial interreader agreement in overall scoring in patients with suspicious prostate cancer, with a similar level of agreement to version 1.

Risk Stratification of Prostate Cancer According to PI-RADS® Version 2 Categories: Meta-Analysis for Prospective Studies.

PURPOSE: The Prostate Imaging Reporting and Data System (PI-RADS) version 2 (v2) categorizes the likelihood of clinically significant prostate cancer on magnetic resonance imaging and determines the diagnostic pathway. We determined clinically significant prostate cancer and all prostate cancer detection rates in each PI-RADS v2 category. MATERIALS AND METHODS: MEDLINE®, EMBASE® and Cochrane databases were searched for prospective studies reporting the detection rates of clinically significant prostate cancer or all prostate cancer. Random effects models were used to determine pooled detection rates of clinically significant prostate cancer and all prostate cancer for each PI-RADS category. The risk of bias was assessed with the Quality Assessment of Diagnostic Accuracy Studies-2. Meta-regression analysis was performed to identify factors affecting study heterogeneity. RESULTS: Thirteen prospective studies including 4,265 men who underwent magnetic resonance imaging targeted biopsy and/or systematic biopsy for a PI-RADS v2 category 3 or greater, or systematic biopsy for PI-RADS 1-2 were included. The pooled detection rates of clinically significant prostate cancer monotonically increased for each PI-RADS v2 category, ie 4% (95% CI 2-8) for category 1-2, 17% (95% CI 13-21) for category 3, 46% (95% CI 38-55) for category 4 and 75% (95% CI 73-78) for category 5. Substantial study heterogeneity was noted in clinically significant prostate cancer detection rates for categories 1-2 and 4, which were significantly affected by study subject selection (biopsy naïve patients only or not) and studies with a high risk of bias. CONCLUSIONS: PI-RADS v2 can be useful for the stratification of the risk of clinically significant prostate cancer in patients at risk for prostate cancer but the limitations in category 4 still remain.

Direct Comparison of PI-RADS Version 2 and 2.1 in Transition Zone Lesions for Detection of Prostate Cancer: Preliminary Experience.

BACKGROUND: There appears to be less agreement in the identification of cancers in the transition zone (TZ), which is not as reliable as those in peripheral zone when using the Prostate Imaging Reporting and Data System (PI-RADS) version 2 (v2). In response to such shortcomings, the updated version 2.1 was introduced, which incorporated diffusion-weighted imaging (DWI) into category 2 and clarified lexicons. PURPOSE: To compare the diagnostic performance for the detection of clinically significant TZ prostate cancers (csPCa) and interreader agreement between PI-RADS v2.1 and v2. STUDY TYPE: Retrospective study. POPULATION: In all, 142 patients, 201 TZ lesions. FIELD STRENGTH/SEQUENCE: 3.0T; T2 -weighted image and DWI. ASSESSMENT: Lesions were scored by three independent readers using PI-RADS v2 and v2.1. STATISTICAL TESTS: The sensitivity and specificity at category ≥3 were compared between v2 and v2.1 using the generalized estimating equation model. Detection rates for csPCa of upgraded and downgraded lesions in the use of PI-RADS v2.1 from v2 were assessed. Interreader agreement was assessed using κ statistics. RESULTS: PI-RADS v2.1 showed a higher sensitivity and specificity (94.5% and 60.9%) than v2 (91.8% and 56.3%) for category ≥3 lesions in the detection of csPCa, although not significantly. Of eight upgraded lesions from category 2 to 3 (2 + 1) with an incorporated DWI, 50% (4/8) were csPCa. This was significantly higher than category 2 lesions (4.4%; P = 0.003). No csPCa was detected among the 22.8% (46/201) downgraded lesions. There was a moderate interreader agreement for scores ≥3 (κ = 0.565) in v2.1, which was slightly higher than that for v2 (κ = 0.534), although not significantly. DATA CONCLUSION: PI-RADS v2.1 provides moderate and comparable interreader agreement at category ≥3 than v2 in the TZ lesions. Upgraded lesions from category 2 to 3 demonstrated a higher detection rate of csPCa than category 2 lesions in v2.1. LEVEL OF EVIDENCE: 4 TECHNICAL EFFICACY STAGE: 2 J. Magn. Reson. Imaging 2020;52:577-586.

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.

Temporal Changes in In Vivo Glutamate Signal during Demyelination and Remyelination in the Corpus Callosum: A Glutamate-Weighted Chemical Exchange Saturation Transfer Imaging Study.

BACKGROUND: Glutamate-weighted chemical exchange saturation transfer (GluCEST) is a useful imaging tool that can be used to detect changes in glutamate levels in vivo and could also be helpful in the diagnosis of brain myelin changes. We investigated glutamate level changes in the cerebral white matter of a rat model of cuprizone-administered demyelination and remyelination using GluCEST. METHOD: We used a 7 T pre-clinical magnetic resonance imaging (MRI) system. The rats were divided into the normal control (CTRL), cuprizone-administered demyelination (CPZDM), and remyelination (CPZRM) groups. GluCEST data were analyzed using the conventional magnetization transfer ratio asymmetry in the corpus callosum. Immunohistochemistry and transmission electron microscopy analyses were also performed to investigate the myelinated axon changes in each group. RESULTS: The quantified GluCEST signals differed significantly between the CPZDM and CTRL groups (-7.25 ± 1.42% vs. -2.84 ± 1.30%; p = 0.001). The increased GluCEST signals in the CPZDM group decreased after remyelination (-6.52 ± 1.95% in CPZRM) to levels that did not differ significantly from those in the CTRL group (p = 0.734). CONCLUSION: The apparent temporal signal changes in GluCEST imaging during demyelination and remyelination demonstrated the potential usefulness of GluCEST imaging as a tool to monitor the myelination process.

Cerebral mapping of glutamate using chemical exchange saturation transfer imaging in a rat model of stress-induced sleep disturbance at 7.0T.

BACKGROUND: Glutamate chemical exchange saturation transfer (GluCEST) imaging has been widely used in brain psychiatric disorders. Glutamate signal changes may help to evaluate the sleep-related disorders, and could be useful in diagnosis. PURPOSE: To evaluate signal changes in the hippocampus and cortex of a rat model of stress-induced sleep disturbance using GluCEST. STUDY TYPE: Prospective animal study. ANIMAL MODEL: Fourteen male Sprague-Dawley rats. FIELD STRENGTH/SEQUENCE: 7.0T small bore MRI / fat-suppressed, turbo-rapid acquisition with relaxation enhancement (RARE) for CEST, and spin-echo, point-resolved proton MR spectroscopy (1 H MRS). ASSESSMENT: Rats were divided into two groups: the stress-induced sleep-disturbance group (SSD, n = 7) and the control group (CTRL, n = 7), to evaluate and compare the cerebral glutamate signal changes. GluCEST data were quantified using a conventional magnetization transfer ratio asymmetry in the left- and right-side hippocampus and cortex. The correlation between GluCEST signal and glutamate concentrations, derived from 1 H MRS, was evaluated. STATISTICAL ANALYSIS: Wilcoxon rank-sum test between CEST signals and multiparametric MR signals, Wilcoxon signed-rank test between CEST signals on the left and right hemispheres, and a correlation test between CEST signals and glutamate concentrations derived from 1 H MRS. RESULTS: Measured GluCEST signals showed significant differences between the two groups (left hippocampus; 4.23 ± 0.27% / 5.27 ± 0.42% [SSD / CTRL, P = 0.002], right hippocampus; 4.50 ± 0.44% / 5.04 ± 0.34% [P = 0.035], left cortex; 2.81 ± 0.38% / 3.56 ± 0.41% [P = 0.004], and right cortex; 2.95 ± 0.47% / 3.82 ± 0.26% [P = 0.003]). GluCEST signals showed positive correlation with glutamate concentrations (R2 = 0.312; P = 0.038). DATA CONCLUSION: GluCEST allowed the visualization of cerebral glutamate changes in rats subjected to sleep disturbance, and may yield valuable insights for interpreting alterations in cerebral biochemical information. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;50:1866-1872.

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.

Sonographic Features of Small (< 4 cm) Renal Tumors With Low Signal Intensity on T2-Weighted MR Images: Differentiating Minimal-Fat Angiomyolipoma From Renal Cell Carcinoma.

OBJECTIVE: The purpose of this study is to characterize and assess the diagnostic utility of sonographic features of minimal-fat angiomyolipoma (AML) and renal cell carcinoma (RCC) with regard to small (< 4 cm) renal masses with a predominantly low signal intensity (SI) on T2-weighted MR images. MATERIALS AND METHODS: Fifty small renal masses with a predominantly low SI on T2-weighted MR images and no macroscopic fat, all of which had US images available, were assessed. MRI variables (T2 ratio, signal intensity index [SII], and tumor-to-spleen ratio on chemical-shift images), CT features (enhancement patterns and attenuations values on unenhanced images and images obtained in the corticomedullary and nephrographic phases), and sonographic features (echogenicity, heterogeneity, and the presence of acoustic shadowing, a hypoechoic rim, or an intratumoral cyst) were recorded in a blinded manner. Echo-genicity was classified as hypo-, iso-, or hyperechoic compared with the renal parenchyma or markedly hyperchoic when equivalent to that of the renal sinus fat. RESULTS: Minimal-fat AML and RCC were confirmed in 22 and 28 patients, respectively. T2 ratios were significantly lower for minimal-fat AML versus RCCs (p = 0.044). Minimal-fat AMLs exhibited echogenicities that were considered hypoechoic (31.8%), isoechoic (4.5%), hyperechoic (18.2%), or markedly hyperechoic (45.5%). No RCC showed marked hyperechogenicity. CT attenuation values were significantly higher for the minimal-fat AMLs seen in all imaging phases. When the combination of the T2 ratio, nephrographic phase attenuation, and echogenicity was assessed, the AUC value was 0.93 (95% CI, 0.81-0.98), which was a significant increase over the AUC value of 0.83 (95% CI, 0.69-0.92) for noted the combination of the T2 ratio and nephrographic phase attenuation. CONCLUSION: Additional reviews of the echogenicity of small renal masses with low SI on T2-weighted MR images may aid the diagnosis of minimal-fat AML.

Gastric-Type Adenocarcinoma of the Uterine Cervix: Magnetic Resonance Imaging Features, Clinical Outcomes, and Prognostic Factors.

OBJECTIVE: Gastric-type mucinous adenocarcinoma (GAS) of uterine cervix has been suggested as distinct clinicopathologic behavior. Our study aimed to investigate the distinguishing imaging features and clinical outcomes of GAS. METHODS: Fifteen cases of GAS and 45 cases of 3:1 age-matched usual-type endocervical carcinoma (UEA) were assessed. Clinical parameters (age, tumor size, clinical stage, and time to recurrence [TTR] or death) and pathologic results confirmed by surgery were recorded. Imaging features (tumor shape, margin, presence of vaginal involvement, or cyst) on magnetic resonance T2-weighed images were evaluated by consensus reading. Parametrial invasion was assessed by 2 independent readers on a 4-point scale system. RESULTS: Gastric-type mucinous adenocarcinomas were associated with a higher stage at presentation and higher rates of deep cervical stromal invasion, parametrial invasion, and lymphovascular invasion. On magnetic resonance images, GASs also demonstrated a more infiltrative shape (93.3% vs 22.2%; P < 0.001) with/without cysts, ill-defined margin (93.3% vs 31.8%; P < 0.001), endocervical location (46.7%) or extension to the entire cervix (46.7%), higher rates of vaginal involvement (40.0% vs 4.4%; P = 0.002), and higher grade of parametrial invasion by both readers (66.7% vs 22.2%; P = 0.003) compared with UEAs. Patients with GAS had a significantly shorter TTR compared with UEA cases (P < 0.001) by log-rank test. A multivariate Cox proportional hazards model revealed that an infiltrative tumor shape (hazard ratio, 5.92; P = 0.004) and stage II or greater (hazard ratio, 4.19; P = 0.011) were prognostic indicators of a shorter TTR. CONCLUSIONS: Gastric-type mucinous adenocarcinoma may have characteristic imaging features and poorer outcomes compared with UEA.

Measurement of arterial transit time and renal blood flow using pseudocontinuous ASL MRI with multiple post-labeling delays: Feasibility, reproducibility, and variation.

PURPOSE: To evaluate the feasibility, reproducibility, and variation of renal perfusion and arterial transit time (ATT) using pseudocontinuous arterial spin labeling magnetic resonance imaging (PCASL MRI) in healthy volunteers. MATERIALS AND METHODS: PCASL MRI at 3T was performed in 25 healthy volunteers on two different occasions. The ATT and ATT-corrected renal blood flow (ATT-cRBF) were calculated at four different post-labeling delay points (0.5, 1.0, 1.5, and 2.0 s) and evaluated for each kidney and subject. The intraclass correlation (ICC) and Bland-Altman plot were used to assess the reproducibility of the PCASL MRI technique. The within-subject coefficient of variance was determined. RESULTS: Results were obtained for 46 kidneys of 23 subjects with a mean age of 38.6 ± 9.8 years and estimated glomerular filtration rate (eGFR) of 89.1 ± 21.2 ml/min/1.73 m2 . Two subjects failed in the ASL MRI examination. The mean cortical and medullary ATT-cRBF for the subjects were 215 ± 65 and 81 ± 21 ml/min/100 g, respectively, and the mean cortical and medullary ATT were 1141 ± 262 and 1123 ± 245 msec, correspondingly. The ICC for the cortical ATT-cRBF was 0.927 and the within-subject coefficient of variance was 14.4%. The ICCs for the medullary ATT-cRBF and the cortical and medullary ATT were poor. The Bland-Altman plot for cortical RBF showed good agreement between the two measurements. CONCLUSION: PCASL MRI is a feasible and reproducible method for measuring renal cortical perfusion. In contrast, ATT for the renal cortex and medulla has poor reproducibility and high variation. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 2 J. MAGN. RESON. IMAGING 2017;46:813-819.