Adaptation of the Tumor Antigen Presentation Machinery to Ionizing Radiation.

Ionizing radiation (IR) can reprogram proteasome structure and function in cells and tissues. In this article, we show that IR can promote immunoproteasome synthesis with important implications for Ag processing and presentation and tumor immunity. Irradiation of a murine fibrosarcoma (FSA) induced dose-dependent de novo biosynthesis of the immunoproteasome subunits LMP7, LMP2, and Mecl-1, in concert with other changes in the Ag-presentation machinery (APM) essential for CD8+ T cell-mediated immunity, including enhanced expression of MHC class I (MHC-I), ß2-microglobulin, transporters associated with Ag processing molecules, and their key transcriptional activator NOD-like receptor family CARD domain containing 5. In contrast, in another less immunogenic, murine fibrosarcoma (NFSA), LMP7 transcripts and expression of components of the immunoproteasome and the APM were muted after IR, which affected MHC-I expression and CD8+ T lymphocyte infiltration into NFSA tumors in vivo. Introduction of LMP7 into NFSA largely corrected these deficiencies, enhancing MHC-I expression and in vivo tumor immunogenicity. The immune adaptation in response to IR mirrored many aspects of the response to IFN-γ in coordinating the transcriptional MHC-I program, albeit with notable differences. Further investigations showed divergent upstream pathways in that, unlike IFN-γ, IR failed to activate STAT-1 in either FSA or NFSA cells while heavily relying on NF-κB activation. The IR-induced shift toward immunoproteasome production within a tumor indicates that proteasomal reprogramming is part of an integrated and dynamic tumor-host response that is specific to the stressor and the tumor and therefore is of clinical relevance for radiation oncology.

Artificial Intelligence Improves the Ability of Physicians to Identify Prostate Cancer Extent.

PURPOSE: Defining prostate cancer contours is a complex task, undermining the efficacy of interventions such as focal therapy. A multireader multicase study compared physicians' performance using artificial intelligence (AI) vs standard-of-care methods for tumor delineation. MATERIALS AND METHODS: Cases were interpreted by 7 urologists and 3 radiologists from 5 institutions with 2 to 23 years of experience. Each reader evaluated 50 prostatectomy cases retrospectively eligible for focal therapy. Each case included a T2-weighted MRI, contours of the prostate and region(s) of interest suspicious for cancer, and a biopsy report. First, readers defined cancer contours cognitively, manually delineating tumor boundaries to encapsulate all clinically significant disease. Then, after ≥ 4 weeks, readers contoured the same cases using AI software. Using tumor boundaries on whole-mount histopathology slides as ground truth, AI-assisted, cognitively-defined, and hemigland cancer contours were evaluated. Primary outcome measures were the accuracy and negative margin rate of cancer contours. All statistical analyses were performed using generalized estimating equations. RESULTS: The balanced accuracy (mean of voxel-wise sensitivity and specificity) of AI-assisted cancer contours (84.7%) was superior to cognitively-defined (67.2%) and hemigland contours (75.9%; P < .0001). Cognitively-defined cancer contours systematically underestimated cancer extent, with a negative margin rate of 1.6% compared to 72.8% for AI-assisted cancer contours (P < .0001). CONCLUSIONS: AI-assisted cancer contours reduce underestimation of prostate cancer extent, significantly improving contouring accuracy and negative margin rate achieved by physicians. This technology can potentially improve outcomes, as accurate contouring informs patient management strategy and underpins the oncologic efficacy of treatment.

Single-shot diffusion trace-weighted MR spectroscopy: Comparison with unipolar and bipolar diffusion-weighted point-resolved spectroscopy.

This study demonstrates the feasibility and performance of the point-resolved spectroscopy (PRESS)-based, single-shot diffusion trace-weighted sequence in quantifying the trace apparent diffusion coefficient (ADC) in phantom and in vivo using a 3-T MRI/MRS scanner. The single-shot diffusion trace-weighted PRESS sequence was implemented and compared with conventional diffusion-weighted (DW)-PRESS variants using bipolar and unipolar diffusion-sensitizing gradients. Nine phantom datasets were acquired using each sequence, and seven volunteers were scanned in three different brain regions to determine the range and variability of trace ADC values, and to allow a comparison of trace ADCs among the sequences. This sequence results in a comparatively stable range of trace ADC values that are statistically significantly higher than those produced from unipolar and bipolar DW-PRESS sequences. Only total n-acetylaspartate, total creatine, and total choline were reliably estimated in all sequences with Cramér-Rao lower bounds of, at most, 20%. The larger trace ADCs from the single-shot sequences are probably attributable to the shorter diffusion time relative to the other sequences. Overall, this study presents the first demonstration of the single-shot diffusion trace-weighted sequence in a clinical scanner at 3 T. The results show excellent agreement of phantom trace ADCs computed with all sequences, and in vivo ADCs agree well with the expected differences between gray and white matter. The diffusion trace-weighted sequence could provide an estimate of the trace ADC in a shorter scan time (by nearly a factor of 3) compared with conventional DW-PRESS approaches that require three separate orthogonal directions.

Safety and Effectiveness of Track Cauterization for Lung Cryoablation.

PURPOSE: To evaluate the safety and effectiveness of track cauterization for lung cryoablation through comparison of postprocedural adverse event (AE) rates. MATERIALS AND METHODS: Fifty-nine patients who underwent 164 percutaneous lung cryoablation procedures between 2013 and 2018 were included in this retrospective study. The study cohort was subdivided by whether track cauterization was conducted or not at the end of the procedure. The study cohort was also subdivided by the number of probes (1-2 probes vs 3-4 probes). Postablation AE rates were assessed by immediate and delayed (at 1 month or later) AEs, pneumothorax, hemothorax, pleural effusion, and whether intervention was required. Univariate and multivariate logistic regression analyses were used to compare differences in AE rates. RESULTS: Patients who underwent procedures with track cautery were 2.6 times less likely to exhibit pleural effusion (P = .017). Patients who underwent procedures conducted with a higher number of probes were 3.8 times more likely to receive interventions (P < .001), 1.6 times more likely to experience pneumothorax (P = .037), and 2.1 times more likely to experience pleural effusion (P = .003). History of lung surgery, increased number of probes, size of the probe, and absence of track cautery were noted to be significant predictors of AEs and need for interventions (all P < .05). CONCLUSIONS: Track cauterization in lung cryoablation was proven to reduce pleural effusion, but no difference in pneumothorax or delayed AEs was noted. The use of fewer probes was associated with a lower rate of AEs.

CT-monitored minimal ablative margin control in single-session microwave ablation of liver tumors: an effective strategy for local tumor control.

OBJECTIVES: To investigate the usefulness of minimal ablative margin (MAM) control by intra-procedural contrast-enhanced CT (CECT) in microwave ablation (MWA) of liver tumors. METHODS: A total of 334 consecutive liver tumors (240 hepatocellular carcinomas [HCCs] and 94 colorectal liver metastases [CRLMs]) in 172 patients treated with percutaneous MWA were retrospectively included. MAM of each tumor was assessed after expected ablation completion using intra-procedural CECT, allowing within-session additional ablation to any potentially insufficient margin. On immediate post-MWA MRI, complete ablation coverage of tumor and final MAM status were determined. The cumulative local tumor progression (LTP) rate was estimated by using the Kaplan-Meier method. To identify predictors of LTP, Cox regression analysis with a shared frailty model was performed. RESULTS: Intra-procedural CECT findings prompted additional ablation in 18.9% (63/334) of tumors. Final complete ablation coverage of tumor and sufficient MAM were determined by MRI to be achieved in 99.4% (332/334) and 77.5% (259/334), and their estimated 6-month, 1-year, and 2-year LTP rates were 3.2%, 7.5%, and 12.9%; and 1.0%, 2.1%, and 6.9%, respectively. Insufficient MAM on post-MWA MRI, perivascular tumor location, and tumor size (cm) were independent risk factors for LTP (hazard ratio = 14.4, 6.0, and 1.1, p < 0.001, p = 0.003, and p = 0.011, respectively), while subcapsular location and histology (HCC vs CRLM) were not. CONCLUSIONS: In MWA of liver tumors, intra-procedural CECT monitoring of minimal ablative margin facilitates identification of potentially suboptimal margins and guides immediate additional intra-session ablation to maximize rates of margin-sufficient ablations, the latter being a highly predictive marker for excellent long-term local tumor control. KEY POINTS: • In MWA of liver tumors, intra-procedural CECT can identify potentially suboptimal minimal ablative margin, leading to immediate additional ablation in a single treatment session. • Achieving a finally sufficient ablative margin through the MWA with intra-procedural CECT monitoring of minimal ablative margin results in excellent local tumor control.

Development, diagnostic performance, and interobserver agreement of a 18F-flurpiridaz PET automated perfusion quantitation system.

BACKGROUND: Computerized methodologies standardize the myocardial perfusion imaging (MPI) interpretation process. METHODS: To develop an automated relative perfusion quantitation approach for 18F-flurpiridaz, PET MPI studies from all phase III trial participants of 18F-flurpiridaz were divided into 3 groups. Count distributions were obtained in N = 40 normal patients undergoing pharmacological or exercise stress. Then, N = 90 additional studies were selected in a derivation group. Following receiver operating characteristic curve analysis, various standard deviations below the mean normal were used as cutoffs for significant CAD, and interobserver variability determined. Finally, diagnostic performance was compared between blinded visual readers and blinded derivations of automated relative quantitation in the remaining N = 548 validation patients. RESULTS: Both approaches yielded comparable accuracies for the detection of global CAD, reaching 71% and 72% by visual reads, and 72% and 68% by automated relative quantitation, when using CAD ≥ 70% or ≥ 50% stenosis for significance, respectively. Similar results were observed when analyzing individual coronary territories. In both pharmacological and exercise stress, automated relative quantitation demonstrated significantly more interobserver agreement than visual reads. CONCLUSIONS: Our automated method of 18F-flurpiridaz relative perfusion analysis provides a quantitative, objective, and highly reproducible assessment of PET MPI in normal and CAD subjects undergoing either pharmacological or exercise stress.

Omega-3 fatty acids increase OXPHOS energy for immune therapy of Alzheimer disease patients.

Sporadic late-onset Alzheimer disease (LOAD) preceded by mild cognitive impairment (MCI) is the most common type of dementia. Long-term studies of immunity to pathogenic amyloid-ß (Aß) in LOAD are lacking. Innate immunity of LOAD patients is malfunctioning in phagocytosis and degradation of Aß and LOAD patients' macrophage transcriptome and metabolome are deregulated. We previously showed omega-3 fatty acid (ω-3)-mediated repair of unfolded protein response and here we show much broader transcriptomic effects. ω-3 treatment in vitro and ω-3 supplementation by the drink Smartfish (SMF) in vivo increased the transcripts of the genes and pathways of immunity, glycolysis, tricarboxylic acid cycle, OX-PHOS, nicotinamide dinucleotide (NAD+ ) synthesis, and reversed the defects in Aß phagocytosis. In both peripheral blood mononuclear cells (PBMC) and macrophages, ω-3 increased ATP-linked oxygen consumption rate (OCR) and ω-3 with carnitine was superior to ω-3. ω-3 treatment in vitro and supplementation by the ω-3 drink SMF in vivo rescued macrophage phagocytosis when glycolysis or glycosylation were blocked. ω-3 provide flexible energy for immune clearance of the brain throughout the diurnal cycle, even in hypo- or hyper-glycemia. In certain LOAD patients, ω-3 may delay progression to dementia.

Yttrium-90 radiation segmentectomy for hepatic metastases: A multi-institutional study of safety and efficacy.

BACKGROUND AND OBJECTIVES: This study assessed the outcomes of Yttrium-90 (90 Y) radiation segmentectomy for hepatic metastases unamenable to resection or ablation. MATERIALS AND METHODS: Over 6 years, 36 patients with 53 tumors underwent segmental radioembolization. Patients were not candidates for surgical resection or thermal ablation. Malignancies included metastases from colorectal cancer (31%), neuroendocrine tumors (28%), sarcoma (19%), and others (22%). Eighty-one percent of patients had undergone prior treatment with systemic chemotherapy. Ongoing systemic chemotherapy was continued. Toxicity, tumor response, tumor progression, and survival were assessed. RESULTS: The median tumor size was 3.6 cm (range 1.2-6.1 cm). Adverse event rates were low, with no hepatic-related Common Terminology Criteria for Adverse Events Grade 3 or 4 toxicity. Target tumor Response Evaluation Criteria in Solid Tumors disease control rate was 92% (28% partial response, 64% stable disease). For patients with enhancing tumors (n = 14), modified Response Evaluation Criteria in Solid Tumors target tumor objective response rate was 100%. During a median follow-up of 12 months, target tumor progression occurred in 28% of treated tumors. Overall survival was 96% and 83% at 6 and 12 months, respectively. CONCLUSIONS: 90 Y radiation segmentectomy for hepatic metastases demonstrates high rates of tumor control and minimal toxicity. Radiation segmentectomy should be considered for patients with metastatic hepatic malignancy who are not candidates for surgical resection.

Image-Guided Percutaneous Thermal Ablation of Oligometastatic Ovarian and Non-Ovarian Gynecologic Tumors.

PURPOSE: To assess the safety, feasibility, and efficacy of percutaneous thermal ablation (TA) in the treatment of metastatic gynecologic (GYN) tumors. MATERIALS AND METHODS: A study cohort of 42 consecutive women (mean age, 59. years; range, 25-78 years) with metastatic GYN tumors (119 metastatic tumors) treated with radiofrequency (n = 47 tumors), microwave (n = 47 tumors), or cryogenic (n = 30 tumors) ablation from over 2,800 ablations performed from January 2001 to January 2019 was identified. The primary GYN neoplasms consisted of ovarian (27 patients; 77 tumors; mean tumor diameter [MTD], 2.50 cm), uterine (7 patients; 26 tumors; MTD, 1.89 cm), endometrial (5 patients; 10 tumors; MTD, 2.8 cm), vaginal (2 patients; 5 tumors; MTD, 2.40 cm), and cervical (1 patient; 1 tumor; MTD, 1.90 cm) cancers. In order of descending frequency, metastatic tumors treated by TA were located in the liver or liver capsule (74%), lungs (13%), and peritoneal implants (9%). Single tumors were also treated in the kidneys, rectus muscle, perirectal soft tissue (2.5%), and retroperitoneal lymph nodes (1.6%). All efficacy parameters of TA and definitions of major and minor adverse events are categorized by the latest Society of Interventional Radiology reporting standards. RESULTS: The median follow-up of treated patients was 10 months. After the initial ablation, 95.6% of the patients achieved a complete tumor response confirmed by contrast-enhanced magnetic resonance imaging or computed tomography. On surveillance imaging, 8.5% of the ablated tumors developed local progression over a median follow-up period of 4.1 months. Five of 8 tumors with local recurrence underwent repeated treatment over a mean follow-up period of 18 months, and 4 of 5 tumors achieved complete eradication after 1 additional treatment session that resulted in a secondary efficacy of 80%. The overall technique efficacy of TA was 96.2% over a median follow-up period of 10 months. CONCLUSIONS: TA was safe and effective for the local control of metastatic GYN tumors in the lungs, abdomen, and pelvis, with an overall survival rate of 37.5 months and a local progression-free survival rate of 16.5 months, with only 4.8% of treated patients experiencing a major adverse event.

Efficacy of 3T Multiparametric MR Imaging followed by 3T in-Bore MR-Guided Biopsy for Detection of Clinically Significant Prostate Cancer Based on PIRADSv2.1 Score.

PURPOSE: To evaluate the diagnostic yield of 3T in-Bore magnetic resonance-guided biopsy (3T IB-MRGB) for detection of clinically significant prostate cancer (csPCa), based on assessment using the Prostate Imaging Reporting and Data System version 2.1 (PIRADSv2.1). MATERIALS AND METHODS: This single-center study examined individuals who underwent 3T multiparametric prostate magnetic resonance (MR) imaging and subsequent 3T IB-MRGB. The final study cohort included 379 men (with 475 targets) divided into 3 subcohorts: biopsy-naïve men (n = 123), individuals with a history of negative trans-rectal-ultrasonography (TRUS) biopsy results (n = 106), and men with low-grade PCa under active surveillance (n = 150). csPCa was defined as having a Gleason score (GS) ≥3+4. RESULTS: 3T IB-MRGB detected PCa and csPCa in 69.1% (262 of 379) and 50.3% (193 of 379) of patients, respectively. The PCa and csPCa detection rates per target were 64.2% (305 of 475) and 43.8% (208 of 475), respectively. The rate of urosepsis, treated with intravenous antibiotics, was 1% (4 patients). In TRUS biopsy negative results and biopsy-naïve subcohorts, csPCa was found in 36.8% (39 of 106) and 52.8% (65 of 123), respectively. In 50.7% (76 of 150) of the active surveillance subcohort, 3T IB-MRGB upgraded the GS assigned in prior TRUS biopsies. Positive predictive values of PIRADSv2.1 categories 3, 4, and 5 for csPCa detection were 24.8%, 44.4%, and 67.1%, respectively. Higher PIRADSv2.1 categories were significantly associated with PCa (odds ratio [OR], 3.97; 95% confidence interval [CI], 2.98-5.28) and csPCa (OR, 1.41; 95% CI, 1.03-1.94) detection. Of 137 PIRADSv2 category 3 lesions, 28 were downgraded to PIRADSv2.1 category 2, in which there were no occurrences of csPCa in histology. CONCLUSIONS: Use of 3T IB-MRGB resulted in detection of csPCa in 50.9% of individuals. 3T IB-MRGB has a high diagnostic yield in individuals with negative TRUS biopsy results and those under active surveillance. The PIRADSv2.1 category is a strong predictor of PCa and csPCa detection.

Long-Term Survival after Percutaneous Radiofrequency Ablation of Pathologically Proven Renal Cell Carcinoma in 100 Patients.

PURPOSE: To determine the long-term survival of patients treated with percutaneous radiofrequency (RF) ablation for pathologically proven renal cell carcinoma (RCC). MATERIALS AND METHODS: In this single-center retrospective study, 100 patients with 125 RCCs (100 clear-cell, 19 papillary, and 6 chromophobe) 0.8-8 cm in size treated with RF ablation were evaluated at a single large tertiary-care center between 2004 and 2015. Technical success, primary and secondary technique efficacy, and pre- and postprocedural estimated glomerular filtration rate (eGFR) at 3-6 months and 2-3 years were recorded. Overall survival, cancer-specific survival, and local tumor progression-free survival were calculated by Kaplan-Meier survival curves. Complications were classified per the Clavien-Dindo system. Statistical testing was done via χ2 tests for proportions and paired t test for changes in eGFR. Statistical significance was set at α = 0.05. RESULTS: Overall technical success rate was 100%, and primary and secondary technique efficacy rates were 90% and 100%, respectively. Median follow-up was 62.8 months, ranging from 1 to 120 months. The 10-year overall, cancer-specific, and local progression-free survival rates were 32%, 86%, and 92%, respectively. The number of ablation probes used was predictive of residual unablated tumor (P < .001). There were no significant changes in preprocedure vs 2-3-years postprocedure eGFR (65.2 vs 62.1 mL/min/1.73 m2; P = .443). There was a 9% overall incidence of complications, the majority of which were grade I. CONCLUSIONS: Image-guided percutaneous RF ablation of RCCs is effective at achieving local control and preventing cancer-specific death within 10 years from initial treatment.

3-T Multiparametric MRI Followed by In-Bore MR-Guided Biopsy for Detecting Clinically Significant Prostate Cancer After Prior Negative Transrectal Ultrasound-Guided Biopsy.

OBJECTIVE. The purpose of this study was to evaluate the rate of detection of clinically significant prostate cancer (csPCa), as assessed on the basis of Prostate Imaging Reporting and Data System version 2.1 (PI-RADSv2.1) guidelines, using 3-T in-bore MR-guided biopsy (MRGB) for a cohort of patients suspected of having csPCa despite having a history of recent negative transrectal ultrasound-guided biopsy results. MATERIALS AND METHODS. The cohort in this retrospective, single-center study was derived from a database of 330 patients who underwent multiparametric MRI (mpMRI) followed by in-bore transrectal 3-T MRGB. Seventy-nine patients (mean [± SD] age, 64.1 ± 8.6 years) with prior negative transrectal ultrasound-guided biopsy results and positive pre-MRGB mpMRI results (PI-RADS score ≥ 3) composed the final cohort. The rate of detection of PCa and csPCa (the latter of which was defined by a Gleason score of 3 + 4 or higher) was stratified according to updated PI-RADSv2.1 assessment. RESULTS. MRGB detected PCa in 36 patients (45.6%), 30 (83.3%) of whom had csPCa. The PI-RADSv2.1 score was a strong predictor (odds ratio, 3.97; 95% CI, 1.93-7.47) of csPCa detection. We found two benign transition zone target lesions that were downgraded from PI-RADSv2 category 3 to PI-RADSv2.1 category 2. PCa was detected in 18.4% (7/38), 65.2% (15/23), and 87.5% (14/16) of individuals with PI-RADSv2.1 category 3, 4, and 5 lesions, respectively, with 85.7% (6/7), 86.7% (13/15), and 78.6% (11/14) of these cases found to be csPCa, respectively. Of the seven PI-RADSv2.1 category 3 csPCa lesions, six had prostate-specific antigen density greater than 0.10 ng/mL/cc. CONCLUSION. With the use of 3-T in-bore MRGB, csPCa was detected in 38% of individuals with prior negative transrectal ultrasound-guided biopsy results. PI-RADSv2.1 was a strong predictor of csPCa detection. On the basis of our results, patients with PI-RADSv2.1 category 4 or 5 lesions and patients with PI-RADSv2.1 category 3 lesions and a prostate-specific antigen density greater than or equal to 0.10 ng/mL/cc may benefit from in-bore MRGB.

Cirrhotic Nodule Transformation to Hepatocellular Carcinoma: Natural History and Predictive Biomarkers on Contrast-Enhanced Ultrasound.

OBJECTIVE. The objective of our study was to identify sonographic biomarkers predicting or indicating eventual malignant transformation of pathologically confirmed cirrhotic nodules. MATERIALS AND METHODS. Thirty-nine consecutive patients with 44 pathologically confirmed cirrhotic nodules (mean size, 17.5 ± 8.5 [SD] mm) who initially underwent contrast-enhanced ultrasound examination at detection and then underwent follow-up conventional ultrasound every 3-4 months thereafter were retrospectively included. Malignant transformation was identified on the basis of noninvasive diagnostic criteria for hepatocellular carcinoma or rebiopsy. Malignant transformation biomarkers were identified from clinical and sonographic variables and the performance thereof was evaluated using ROC curves. RESULTS. Fourteen nodules (31.8%) had eventual malignant transformation after a median follow-up time of 26.7 months. At initial detection, nodule size (hazard ratio [HR], 1.07; p = 0.019) and a contrast arrival time difference between the nodule and liver of more than 0.5 second (HR, 4.35; p = 0.011) were independent predictors for malignant transformation. The area under the ROC curve (Az) of initial nodule size (Az = 0.64, p = 0.131) and contrast arrival time difference between the nodule and liver (Az = 0.66, p = 0.029) improved after combining the two (Az = 0.75, p = 0.002). During follow-up, echogenicity change (p = 0.044), absolute growth rate (p < 0.001), and relative growth rate (p < 0.001) correlated with malignant transformation. Sensitivity analysis revealed that an absolute growth rate of 5 mm or greater in 6 months or a relative growth rate of 30% or greater in 6 months could be considered as threshold growth for identifying malignant transformation (specificity, 100.0%; positive predictive value, 100.0%). The absence of both echogenicity change and threshold growth was highly accurate in excluding malignant transformation (sensitivity, 100.0%; negative predictive value, 100.0%). CONCLUSION. The contrast arrival time difference between the nodule and liver at initial detection was useful in stratifying eventual malignant transformation risk for cirrhotic nodules. During follow-up, growth rate and echogenicity change correlated with malignant transformation; threshold growth on ultrasound may be considered a potential major feature in noninvasive diagnostic criteria of hepatocellular carcinoma.

Influence of the Location and Zone of Tumor in Prostate Cancer Detection and Localization on 3-T Multiparametric MRI Based on PI-RADS Version 2.

OBJECTIVE. The objective of our study was to determine the performance of 3-T multiparametric MRI (mpMRI) for prostate cancer (PCa) detection and localization, stratified by anatomic zone and level, using Prostate Imaging Reporting and Data System version 2 (PI-RADSv2) and whole-mount histopathology (WMHP) as reference. MATERIALS AND METHODS. Multiparametric MRI examinations of 415 consecutive men were compared with thin-section WMHP results. A genitourinary radiologist and pathologist collectively determined concordance. Two radiologists assigned PI-RADSv2 scores and sector location to all detected foci by consensus. Tumor detection rates were calculated for clinical and pathologic (tumor location and zone) variables. Both rigid and adjusted sector-matching models were used to account for fixation-related issues. RESULTS. Of 863 PCa foci in 16,185 prostate sectors, the detection of overall and index PCa lesions in the midgland, base, and apex was 54.9% and 83.1%, 42.1% and 64.0% (p = 0.04, p = 0.02), and 41.9% and 71.4% (p = 0.001, p = 0.006), respectively. Tumor localization sensitivity was highest in the midgland compared with the base and apex using an adjusted match compared with a rigid match (index lesions, 71.3% vs 43.7%; all lesions, 70.8% vs 36.0%) and was greater in the peripheral zone (PZ) than in the transition zone. Three-Tesla mpMRI had similarly high specificity (range, 93.8-98.3%) for overall and index tumor localization when using both rigid and adjusted sector-matching approaches. CONCLUSION. For 3-T mpMRI, the highest sensitivity (83.1%) for detection of index PCa lesions was in the midgland, with 98.3% specificity. Multiparametric MRI performance for sectoral localization of PCa within the prostate was moderate and was best for index lesions in the PZ using an adjusted model.

Repeatability and reproducibility of variable flip angle T1 quantification in the prostate at 3 T.

BACKGROUND: Variable flip angle (VFA) imaging is widely used for the estimation of T1 relaxation in the prostate, but may have limited repeatability and reproducibility due to its sensitivity to B1 + inhomogeneity. PURPOSE: To assess the repeatability and reproducibility of prostate T1 estimation with and without compensating for B1 + variation. STUDY TYPE: Prospective. POPULATION: Twenty-one volunteers were prospectively recruited and scanned twice on two 3 T MRI scanners, resulting in 84 VFA T1 exams. FIELD STRENGTH/SEQUENCE: 3 T/2D saturated turbo fast low angle shot (FLASH) and 3D dual-echo FLASH. ASSESSMENT: Two B1 + mapping techniques, including reference region VFA (RR-VFA) and saturated turbo FLASH (satTFL), were used for B1 + correction, and T1 maps with and without B1 + correction were tested for intrascanner repeatability and interscanner reproducibility. Volumetric regions of interest (ROIs) were drawn on the transition zone, peripheral zone of the prostate, and the obturator internus left and right muscles in the corresponding slices. STATISTICAL TESTS: The average T1 within each ROI for each scan was compared for both intra- and interscanner variability using concordance correlation coefficient and a Bland-Altman plot. RESULTS: Both RR-VFA-corrected T1 and satTFL-corrected T1 showed higher intra- and interscanner correlation (0.89/0.87 and 0.87/0.84, respectively) than VFA T1 (0.84 and 0.74). Bland-Altman plots showed that VFA T1 had wider 95% limits of agreement and a larger range of T1 for each tissue compared with T1 with B1 + correction. DATA CONCLUSION: The application of B1 + correction (both RR-VFA and satTFL) to VFA T1 results in more repeatable and reproducible T1 estimation than VFA T1 . This can potentially provide improved quantification of the prostate dynamic contrast-enhanced MRI parameters. Level of Evidence 1. Technical Efficacy Stage 1. J. Magn. Reson. Imaging 2018.

Utility of Multiparametric MRI for Predicting Residual Clinically Significant Prostate Cancer After Focal Laser Ablation.

OBJECTIVE. The purpose of this study was to compare in a multireader manner the diagnostic accuracies of 3-T multiparametric MRI interpretation and serial prostate-specific antigen (PSA) measurement in predicting the presence of residual clinically significant prostate cancer after focal laser ablation. MATERIALS AND METHODS. Eighteen men had undergone focal laser ablation for low- or intermediate-risk prostate cancer as part of two National Cancer Institute-funded phase 1 clinical trials. Multiparametric MRI was performed immediately after and 6 and 12 months after focal laser ablation. Serial PSA measurements after focal laser ablation were recorded, and MRI-ultrasound fusion biopsy was performed 6 and 12 months after ablation and served as the reference standard. Multiparametric MRI was performed at 3 T with pelvic phased-array coils. T2-weighted, DW, and dynamic contrast-enhanced MR images were retrospectively assessed by two blinded radiologists using a 3-point Likert scale (0-2). Inter-reader agreement was assessed with the Cohen kappa statistic. The diagnostic accuracies of multiparametric MRI and PSA measurement were compared. RESULTS. Residual clinically significant prostate cancer was identified in 11 of 18 (61%) men. Logistic regression analysis of serial PSA measurements yielded a correct classification rate of 61.1% (p > 0.05). Using a multiparametric MRI threshold score of 4 or greater, both radiologists made correct classifications for 16 of 18 men (89%) at 6 months and 15 of 17 men (88%) at 12 months. Interreader agreement was substantial to excellent for T2-weighted imaging, DWI, and dynamic contrast-enhanced MRI and improved uniformly from 6 to 12 months. Logistic regression analysis of the retrospectively reviewed multiparametric MR images yielded AUCs greater than 0.90 for each radiologist 6 and 12 months after focal laser ablation (p < 0.001). CONCLUSION. Multiparametric MRI 6 and 12 months after focal laser ablation significantly outperformed serial PSA measurements for predicting the presence of residual clinically significant prostate cancer.

Detection and Localization of Prostate Cancer at 3-T Multiparametric MRI Using PI-RADS Segmentation.

OBJECTIVE. The purpose of this study is to determine the overall and sector-based performance of 3-T multiparametric MRI for prostate cancer (PCa) detection and localization by using Prostate Imaging-Reporting and Data System version 2 (PI-RADSv2) scoring and segmentation compared with whole-mount histopathologic analysis. MATERIALS AND METHODS. Multiparametric 3-T MRI examinations of 415 consecutive men were compared with thin-section whole-mount histopathologic analysis. A genitourinary radiologist and pathologist collectively determined concordance. Two radiologists assigned PI-RADSv2 categories and sectoral location to all detected foci by consensus. Tumor detection rates were calculated for clinical and pathologic (Gleason score) variables. Both rigid and adjusted sector-matching models were used to account for fixation-related issues. RESULTS. The 415 patients had 863 PCa foci (52.7% had a Gleason score ≥ 7, 61.9% were ≥ 1 cm, and 90.4% (375/415) of index lesions were ≥ 1 cm) and 16,185 prostate sectors. Multiparametric MRI enabled greater detection of PCa lesions 1 cm or larger (all lesions vs index lesions, 61.6% vs 81.6%), lesions with Gleason score greater than or equal to 7 (all lesions vs index lesions, 71.4% vs 80.9%), and index lesions with both Gleason score greater than or equal to 7 and size 1 cm or larger (83.3%). Higher sensitivity was obtained for adjusted versus rigid tumor localization for all lesions (56.0% vs 28.5%), index lesions (55.4% vs 34.3%), lesions with Gleason score greater than or equal to 7 (55.7% vs 36.0%), and index lesions 1 cm or larger (56.1% vs 35.0%). Multiparametric 3-T MRI had similarly high specificity (96.0-97.9%) for overall and index tumor localization with adjusted and rigid sector-matching approaches. CONCLUSION. Using 3-T multiparametric MRI and PI-RADSv2, we achieved the highest sensitivity (83.3%) for the detection of lesions 1 cm or larger with Gleason score greater than or equal to 7. Sectoral localization of PCa within the prostate was moderate and was better with an adjusted model than with a rigid model.

Newly Diagnosed Breast Cancer: Comparison of Contrast-enhanced Spectral Mammography and Breast MR Imaging in the Evaluation of Extent of Disease.

Purpose To compare the diagnostic performances of contrast material-enhanced spectral mammography and breast magnetic resonance (MR) imaging in the detection of index and secondary cancers in women with newly diagnosed breast cancer by using histologic or imaging follow-up as the standard of reference. Materials and Methods This institutional review board-approved, HIPAA-compliant, retrospective study included 52 women who underwent breast MR imaging and contrast-enhanced spectral mammography for newly diagnosed unilateral breast cancer between March 2014 and October 2015. Of those 52 patients, 46 were referred for contrast-enhanced spectral mammography and targeted ultrasonography because they had additional suspicious lesions at MR imaging. In six of the 52 patients, breast cancer had been diagnosed at an outside institution. These patients were referred for contrast-enhanced spectral mammography and targeted US as part of diagnostic imaging. Images from contrast-enhanced spectral mammography were analyzed by two fellowship-trained breast imagers with 2.5 years of experience with contrast-enhanced spectral mammography. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value were calculated for both imaging modalities and compared by using the Bennett statistic. Results Fifty-two women with 120 breast lesions were included for analysis (mean age, 50 years; range, 29-73 years). Contrast-enhanced spectral mammography had similar sensitivity to MR imaging (94% [66 of 70 lesions] vs 99% [69 of 70 lesions]), a significantly higher PPV than MR imaging (93% [66 of 71 lesions] vs 60% [69 of 115 lesions]), and fewer false-positive findings than MR imaging (five vs 45) (P < .001 for all results). In addition, contrast-enhanced spectral mammography depicted 11 of the 11 secondary cancers (100%) and MR imaging depicted 10 (91%). Conclusion Contrast-enhanced spectral mammography is potentially as sensitive as MR imaging in the evaluation of extent of disease in newly diagnosed breast cancer, with a higher PPV. © RSNA, 2017.

Longterm follow-up of small pancreatic cystic lesions in liver transplant recipients.

Incidental small pancreatic cystic lesions (PCLs) are often found on preoperative imaging in patients undergoing orthotopic liver transplantation (OLT). Although these are considered benign or of low malignant potential, the influence of immunosuppression after OLT may be of concern. The aim of this study was to observe the longterm outcome of these small PCLs in post-OLT patients. An institutional OLT database of 1778 consecutive OLT patients from January 2000 to December 2010 was analyzed. Computed tomography, magnetic resonance imaging, or endoscopic ultrasound at the time of OLT and all subsequent imaging, cytology, fluid analysis of PCLs, and patient status were evaluated. A total of 70 patients with 182 PCLs, of benign or low malignant potential, were identified with a mean follow-up time of 64 months. At initial diagnosis of PCLs in 48 patients, 7 branch duct-type intraductal papillary mucinous neoplasms (B-IPMNs), 1 serous cystadenoma (SCA), and 40 nonspecific benign cysts were identified. Final diagnosis at the end of the follow-up revealed 16 B-IPMNs, 3 SCAs, and a mixed acinar-neuroendocrine carcinoma, in which the latter developed 9 years after initial diagnosis of B-IPMN. During the follow-up time, average increase in size and number of PCLs were 4.5 mm and 1.4, respectively (P < 0.001 for both). The majority of incidental PCLs in OLT patients showed an indolent behavior despite immunosuppression. Risk of malignancy development was very low and comparable with normal population. Liver Transplantation 23 324-329 2017 AASLD.

Epigenetic changes in T-cell and monocyte signatures and production of neurotoxic cytokines in ALS patients.

We have investigated transcriptional and epigenetic differences in peripheral blood mononuclear cells (PBMCs) of monozygotic female twins discordant in the diagnosis of amyotrophic lateral sclerosis (ALS). Exploring DNA methylation differences by reduced representation bisulfite sequencing (RRBS), we determined that, over time, the ALS twin developed higher abundances of the CD14 macrophages and lower abundances of T cells compared to the non-ALS twin. Higher macrophage signature in the ALS twin was also shown by RNA sequencing (RNA-seq). Moreover, the twins differed in the methylome at loci near several genes, including EGFR and TNFRSF11A, and in the pathways related to the tretinoin and H3K27me3 markers. We also tested cytokine production by PBMCs. The ALS twin's PBMCs spontaneously produced IL-6 and TNF-α, whereas PBMCs of the healthy twin produced these cytokines only when stimulated by superoxide dismutase (SOD)-1. These results and flow cytometric detection of CD45 and CD127 suggest the presence of memory T cells in both twins, but effector T cells only in the ALS twin. The ALS twin's PBMC supernatants, but not the healthy twin's, were toxic to rat cortical neurons, and this toxicity was strongly inhibited by an IL-6 receptor antibody (tocilizumab) and less well by TNF-α and IL-1ß antibodies. The putative neurotoxicity of IL-6 and TNF-α is in agreement with a high expression of these cytokines on infiltrating macrophages in the ALS spinal cord. We hypothesize that higher macrophage abundance and increased neurotoxic cytokines have a fundamental role in the phenotype and treatment of certain individuals with ALS.-Lam, L., Chin, L., Halder, R. C., Sagong, B., Famenini, S., Sayre, J., Montoya, D., Rubbi L., Pellegrini, M., Fiala, M. Epigenetic changes in T-cell and monocyte signatures and production of neurotoxic cytokines in ALS patients.