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Background Intradiverticular bladder tumors (IDBT) are rare but clinically important, as they are difficult to assess endoscopically due to limited anatomic access and risk of perforation. MRI may be helpful in assessing IDBT and providing relevant staging and prognostic information. Purpose To assess MRI findings of IDBT and their relationship with overall survival. Methods This retrospective study included 31 consecutive patients with IDBT undergoing MRI from 2008 to 2018 identified through electronic medical records and PACS database search. Two radiologists independently assessed the following MRI features: size (>3 vs ≤3 cm), diverticular neck involvement, Vesical Imaging-Reporting and Data System (VI-RADS) score (>3 vs ≤3), perivesical fat infiltration, additional tumors and suspicious pelvic lymph nodes. Overall survival was estimated using Kaplan-Meier analysis; and the relationship with clinicopathological and MRI features was determined using the Cox proportional-hazards regression model. Inter-reader agreement was assessed using intraclass correlation coefficients (ICC) and Cohen's kappa (K). Results Median follow-up was 1044 days (interquartile range, 474–1952 days). Twenty-six (83.9%) patients underwent surgical treatment with or without neoadjuvant chemotherapy. On MRI, greater tumor size (>3 cm), diverticular neck involvement, perivesical extension, and suspicious lymph nodes were associated with lower overall survival (HR = 3.6–8.1 and 4.3–6.3 for the 2 radiologists, p ≤ 0.03). Other clinicopathological or MRI findings were not associated with survival (p = 0.27–0.65). Inter-reader agreement was excellent for tumor size (ICC = 0.991; 95% CI 0.982–0.996), fair for VI-RADS (K = 0.52, 95% CI, 0.22–0.82), and moderate for others (K = 0.61–0.79). Conclusion In patients with IDBT, several MRI features were significantly associated with overall survival. Utilizing all available clinicopathological and imaging information may improve estimation of prognosis.

PURPOSE To evaluate whether a custom programmatic workflow manager reduces reporting turnaround times (TATs) from a body oncologic imaging workflow at a tertiary cancer center. METHODS A custom software program was developed and implemented in the programming language R. Other aspects of the workflow were left unchanged. TATs were measured over a 12-month period (June-May). The same prior 12-month period served as a historical control. Median TATs of magnetic resonance imaging (MRI) and computed tomography (CT) examinations were compared with a Wilcoxon test. A chi-square test was used to compare the numbers of examinations reported within 24 hours and after 72 hours as well as the proportions of examinations assigned according to individual radiologist preferences. RESULTS For all MRI and CT examinations (124,507 in 2019/2020 and 138,601 in 2020/2021), the median TAT decreased from 4 (interquartile range: 1-22 hours) to 3 hours (1-17 hours). Reports completed within 24 hours increased from 78% (124,127) to 89% (138,601). For MRI, TAT decreased from 22 (5-49 hours) to 8 hours (2-21 hours), and reports completed within 24 hours increased from 55% (14,211) to 80% (23,744). For CT, TAT decreased from 3 (1-19 hours) to 2 hours (1-13 hours), and reports completed within 24 hours increased from 84% (82,342) to 92% (99,922). Delayed reports (with a TAT > 72 hours) decreased from 17.0% (4,176) to 2.2% (649) for MRI and from 2.5% (2,500) to 0.7% (745) for CT. All differences were statistically significant ( P < .001). CONCLUSION The custom workflow management software program significantly decreased MRI and CT report TATs.

Vaccination-associated adenopathy is a frequent imaging finding after administration of COVID-19 vaccines that may lead to a diagnostic conundrum in patients with manifest or suspected cancer, in whom it may be indistinguishable from malignant nodal involvement. To help the medical community address this concern in the absence of studies and evidence-based guidelines, this paper offers recommendations developed by a multidisciplinary panel of experts from three of the leading tertiary care cancer centers in the United States. According to these recommendations, some routine imaging examinations, such as those for screening, should be scheduled before or at least 6 weeks after the final vaccination dose to allow for any reactive adenopathy to resolve. However, there should be no delay of other clinically indicated imaging (e.g., for acute symptoms, short-interval treatment monitoring, urgent treatment planning or complications) due to prior vaccination. The vaccine should be administered on the side contralateral to the primary or suspected cancer, and both doses should be administered in the same arm. Vaccination information (date(s) administered, injection site(s), laterality, and type of vaccine) should be included in every pre-imaging patient questionnaire, and this information should be made readily available to interpreting radiologists. Clear and effective communication between patients, radiologists, referring physician teams and the general public should be considered of the highest priority when managing adenopathy in the setting of COVID-19 vaccination. Summary COVID-19-vaccination–related adenopathy is a frequent imaging finding that may lead to a diagnostic conundrum in patients with manifest or suspected cancer, in whom it may be indistinguishable from malignant nodal involvement. This special report offers recommendations developed by a multidisciplinary panel of experts from three of the leading tertiary care cancer centers in the United States.

Purpose Ultrasound-guided biopsy (US biopsy) with 10–12 cores has a suboptimal sensitivity for clinically significant prostate cancer (sigPCa). If US biopsy is negative, magnetic resonance imaging (MRI)–guided biopsy is recommended, despite a low specificity for lesions with score 3–5 on Prostate Imaging Reporting and Data System (PIRADS). Screening and biopsy guidance using an imaging modality with high accuracy could reduce the number of unnecessary biopsies, reducing side effects. The aim of this study was to assess the performance of positron emission tomography/MRI with 68Ga-labeled prostate-specific membrane antigen (PSMA-PET/MRI) to detect and localize primary sigPCa (ISUP grade group 3 and/or cancer core length ≥ 6 mm) and guide biopsy. Methods Prospective, open-label, single-center, non-randomized, diagnostic accuracy study including patients with suspected PCa by elevation of prostate-specific antigen (PSA) level and a suspicious lesion (PIRADS ≥3) on multiparametric MRI (mpMRI). Forty-two patients underwent PSMA-PET/MRI followed by both PSMA-PET/MRI-guided and section-based saturation template biopsy between May 2017 and February 2019. Primary outcome was the accuracy of PSMA-PET/MRI for biopsy guidance using section-based saturation template biopsy as the reference standard. Results SigPCa was found in 62% of the patients. Patient-based sensitivity, specificity, negative and positive predictive value, and accuracy for sigPCa were 96%, 81%, 93%, 89%, and 90%, respectively. One patient had PSMA-negative sigPCa. Eight of nine false-positive lesions corresponded to cancer on prostatectomy and one in six false-negative lesions was negative on prostatectomy. Conclusion PSMA-PET/MRI has a high accuracy for detecting sigPCa and is a promising tool to select patients with suspicion of PCa for biopsy. Trial registration This trial was retrospectively registered under the name “Positron Emission Tomography/Magnetic Resonance Imaging (PET/MRI) Guided Biopsy in Men with Elevated PSA” (NCT03187990) on 06/15/2017 (https://clinicaltrials.gov/ct2/show/NCT03187990).

Background/Aims Small intestinal bacterial overgrowth (SIBO) is a common condition in disorders of gut-brain interaction (DGBI). Recently, a combined scintigraphy-lactulose hydrogen breath test (ScLHBT) was described as an accurate tool diagnosing SIBO. We aim to analyze whether a lactulose nutrient challenge test (NCT), previously shown to separate DGBI from healthy volunteers, is equivalent to ScLHBT in diagnosing SIBO. Methods We studied data of 81 DGBI patients undergoing ScLHBT with 30 g lactulose and 300 mL water as well as NCT with 30 g lactulose and a 400 mL liquid test meal. Differences in proportion of positive SIBO diagnoses according to specified cecal load and time criteria for NCT and ScLHBT, respectively, were tested in an equivalence trial. An odds ratio (OR) range of 0.80-1.25 was considered equivalent. Results Diagnosis of SIBO during NCT was not equivalent to SIBO diagnosis in ScLHBT, considering a hydrogen increase before cecal load of 5.0%, 7.5%, or 10.0%, respectively ([OR, 3.76; 90% CI, 1.99-7.09], [OR, 1.87; 90% CI, 1.06-3.27], and [OR, 1.11; 90% CI, 0.65- 1.89]). Considering only time to hydrogen increase as criterion, the odds of a positive SIBO diagnosis in the NCT (0.65) was lower than in ScLHBT (1.70) (OR, 0.38; 90% CI, 0.23-0.65). Conclusions This study could not show an equivalence of NCT and ScLHBT in diagnosing SIBO. A possible explanation might be the different transit times owing to unequal testing substances. The effect of this deviation in relation to consecutive therapy regimens should be tested in further prospective studies. (J Neurogastroenterol Motil 2020;26:514-520)

Background Brown adipose tissue (BAT) is a thermogenic tissue which can generate heat in response to mild cold exposure. As it constitutes a promising target in the fight against obesity, we need reliable techniques to quantify its activity in response to therapeutic interventions. The current standard for the quantification of BAT activity is [18F]FDG PET/CT. Various sequences in magnetic resonance imaging (MRI), including those measuring its relative fat content (fat fraction), have been proposed and evaluated in small proof-of-principle studies, showing diverging results. Here, we systematically compare the predictive value of adipose tissue fat fraction measured by MRI to the results of [18F]FDG PET/CT. Methods We analyzed the diagnostic reliability of MRI measured fat fraction (FF) for the estimation of human BAT activity in two cohorts of healthy volunteers participating in two prospective clinical trials (NCT03189511, NCT03269747). In both cohorts, BAT activity was stimulated by mild cold exposure. In cohort 1, we performed [18F]FDG PET/MRI; in cohort 2, we used [18F]FDG PET/CT followed by MRI. Fat fraction was determined by 2-point Dixon and 6-point Dixon measurement, respectively. Fat fraction values were compared to SUVmean in the corresponding tissue depot by simple linear regression. Results In total, 33 male participants with a mean age of 23.9 years and a mean BMI of 22.8 kg/m2 were recruited. In 32 participants, active BAT was visible. On an intra-individual level, FF was significantly lower in high-SUV areas compared to low-SUV areas (cohort 1: p

For clinically significant, locally confined prostate cancer, whole-gland radical prostatectomy and radiotherapy are established effective treatment strategies that, however, come at a cost of significant morbidity related to urinary and sexual side effects. The concept of risk stratification paired with a better understanding of prognostic factors has led to the development of alternative management options including active surveillance and focal therapy for appropriately selected patients with localized disease. High-intensity focused ultrasound (HIFU) is one such minimally invasive, image-guided treatment option for prostate cancer. Due to the relative novelty of HIFU and the increased use of magnetic resonance imaging in prostate cancer, many radiologists are not yet familiar with imaging findings related to HIFU, their temporal evolution as well as imaging appearance of recurrent disease after this type of focal therapy. HIFU induces sharply demarcated, localized coagulative necrosis of a tumor through thermal energy delivered via an endorectal or transurethral ultrasound transducer. In this pictorial review, we aim at providing relevant background information that will guide the reader through the general principles of HIFU in the prostate, as well as demonstrate the imaging appearance of expected post-HIFU changes versus recurrent tumor.

IMPORTANCE: Machine learning algorithms enable the automatic classification of cardiovascular diseases based on raw cardiac ultrasound imaging data. However, the utility of machine learning in distinguishing between takotsubo syndrome (TTS) and acute myocardial infarction (AMI) has not been studied. OBJECTIVES: To assess the utility of machine learning systems for automatic discrimination of TTS and AMI. DESIGN, SETTINGS, AND PARTICIPANTS: This cohort study included clinical data and transthoracic echocardiogram results of patients with AMI from the Zurich Acute Coronary Syndrome Registry and patients with TTS obtained from 7 cardiovascular centers in the International Takotsubo Registry. Data from the validation cohort were obtained from April 2011 to February 2017. Data from the training cohort were obtained from March 2017 to May 2019. Data were analyzed from September 2019 to June 2021. EXPOSURE: Transthoracic echocardiograms of 224 patients with TTS and 224 patients with AMI were analyzed. MAIN OUTCOMES AND MEASURES: Area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, and specificity of the machine learning system evaluated on an independent data set and 4 practicing cardiologists for comparison. Echocardiography videos of 228 patients were used in the development and training of a deep learning model. The performance of the automated echocardiogram video analysis method was evaluated on an independent data set consisting of 220 patients. Data were matched according to age, sex, and ST-segment elevation/non-ST-segment elevation (1 patient with AMI for each patient with TTS). Predictions were compared with echocardiographic-based interpretations from 4 practicing cardiologists in terms of sensitivity, specificity, and AUC calculated from confidence scores concerning their binary diagnosis. RESULTS: In this cohort study, apical 2-chamber and 4-chamber echocardiographic views of 110 patients with TTS (mean [SD] age, 68.4 [12.1] years; 103 [90.4%] were female) and 110 patients with AMI (mean [SD] age, 69.1 [12.2] years; 103 [90.4%] were female) from an independent data set were evaluated. This approach achieved a mean (SD) AUC of 0.79 (0.01) with an overall accuracy of 74.8 (0.7%). In comparison, cardiologists achieved a mean (SD) AUC of 0.71 (0.03) and accuracy of 64.4 (3.5%) on the same data set. In a subanalysis based on 61 patients with apical TTS and 56 patients with AMI due to occlusion of the left anterior descending coronary artery, the model achieved a mean (SD) AUC score of 0.84 (0.01) and an accuracy of 78.6 (1.6%), outperforming the 4 practicing cardiologists (mean [SD] AUC, 0.72 [0.02]) and accuracy of 66.9 (2.8%). CONCLUSIONS AND RELEVANCE: In this cohort study, a real-time system for fully automated interpretation of echocardiogram videos was established and trained to differentiate TTS from AMI. While this system was more accurate than cardiologists in echocardiography-based disease classification, further studies are warranted for clinical application.

OBJECTIVE While single sugar tests are controversially discussed, combination tests with meals are gaining more attention. The aim of this study was to analyze the impact of adding a test meal to lactulose hydrogen breath tests (LHBT) on hydrogen values and abdominal symptoms in patients with functional gastrointestinal disorders (FGIDs). METHODS Data of 81 FGID patients between 2014-2018 were analyzed. Patients underwent LHBT with 30 g lactulose + 300 mL water and a nutrient challenge test (NCT) including 400 mL liquid test meal + 30 g lactulose. To statistically assess the effect of a test meal on abdominal symptoms and H2, mixed-effect models were used. RESULTS Adding a test meal to LHBT showed a significant increase in nausea [odds ratio (OR) 1.4; 95% confidence interval (CI), 1.1-1.7], decrease in abdominal pain (OR 0.7; 95% CI, 0.6-0.9), borborygmi (OR 0.5; 95% CI, 0.4-0.6), diarrhea (OR 0.4; 95% CI, 0.3-0.6), and H2 production (estimate -5.3, SE 0.7, P

To assess the frequency of ipsilateral axillary adenopathy on breast MRI after COVID-19 vaccination. To investigate the duration, outcomes, and associated variables of vaccine-related adenopathy.In this retrospective cohort study, our database was queried for patients who underwent breast MRI following COVID-19 vaccination from January 22, 2021, to March 21, 2021. The frequency of ipsilateral axillary adenopathy and possible associated variables were evaluated, including age, personal history of ipsilateral breast cancer, clinical indication for breast MRI, type of vaccine, side of vaccination, number of doses, and number of days between the vaccine and the MRI exam. The outcomes of the adenopathy were investigated, including the duration of adenopathy and biopsy results.A total of 357 patients were included. The frequency of adenopathy on breast MRI was 29% (104/357 patients). Younger patients and shorter time intervals from the second dose of the vaccine were significantly associated with the development of adenopathy (p = 0.002 for both). Most adenopathy resolved or decreased on follow-up, with 11% of patients presenting persistence of adenopathy up to 64 days after the second dose of the vaccine. Metastatic axillary carcinoma was diagnosed in three patients; all three had a current ipsilateral breast cancer diagnosis.Vaccine-related adenopathy is a frequent event after COVID-19 vaccination; short-term follow-up is an appropriate clinical approach, except in patients with current ipsilateral breast cancer. Adenopathy may often persist 4-8 weeks after the second dose of the vaccine, thus favoring longer follow-up periods.• MRI-detected ipsilateral axillary adenopathy is a frequent benign finding after mRNA COVID-19 vaccination. • Axillary adenopathy following COVID-19 vaccination often persists4 weeks after vaccination, favoring longer follow-up periods. • In patients with concurrent ipsilateral breast cancer, axillary adenopathy can represent metastatic carcinoma and follow-up is not appropriate.

BACKGROUND: Cancers of unknown primary (CUP) have traditionally been treated empirically, with a dismal prognosis. Compared with standard diagnostic tests, including CT and MRI, imaging with (18)F-fluorodeoxyglucose (FDG) PET or PET/CT has shown the capacity to better identify the primary tumor site and detect additional sites of metastasis. However, its clinical impact is not well established. We performed a systematic review and meta-analysis of prior studies to assess the impact of FDG-PET or PET/CT on the management of patients with CUP. MATERIALS AND METHODS: Pubmed and EMBASE databases were searched up to February 4, 2021. Studies that reported the proportion of patients with CUP who experienced a management change after FDG-PET or PET/CT were included, and the proportions were pooled using the random-effects model. Study quality was assessed using QUADAS-2. Subgroup analysis was conducted to explore heterogeneity. RESULTS: Thirty-eight studies (involving 2795 patients) were included. The pooled proportion of patients with management changes was 35% (95% confidence interval 31%–40%). There was substantial heterogeneity among the studies (Q-test, p

Prostate gland volume (PGV) should be routinely included in MRI reports of the prostate. The recently updated Prostate Imaging Reporting and Data System (PI-RADS) version 2.1 includes a change in the recommended measurement method for PGV compared to version 2.0. The purpose of this study was to evaluate the agreement of MRI-based PGV calculations with the volumetric manual slice-by-slice prostate segmentation as a reference standard using the linear measurements per PI-RADS versions 2.0 and 2.1. Furthermore, to assess inter-reader agreement for the different measurement approaches, determine the influence of an enlarged transition zone on measurement accuracy and to assess the value of the bullet formula for PGV calculation.Ninety-five consecutive treatment-naive patients undergoing prostate MRI were retrospectively analyzed. Prostates were manually contoured and segmented on axial T2-weighted images. Four different radiologists independently measured the prostate in three dimensions according to PI-RADS v2.0 and v2.1, respectively. MRI-based PGV was calculated using the ellipsoid and bullet formulas. Calculated volumes were compared to the reference manual segmentations using Wilcoxon signed-rank test. Inter-reader agreement was calculated using intraclass correlation coefficient (ICC).Inter-reader agreement was excellent for the ellipsoid and bullet formulas using PI-RADS v2.0 (ICC 0.985 and 0.987) and v2.1 (ICC 0.990 and 0.994), respectively. The median difference from the reference standard using the ellipsoid formula derived PGV was 0.4 mL (interquartile range, -3.9 to 5.1 mL) for PI-RADS v2.0 (p = 0.393) and 2.6 mL (interquartile range, -1.6 to 7.3 mL) for v2.1 (p0.001) with a median difference of 2.2 mL. The bullet formula overestimated PGV by a median of 13.3 mL using PI-RADS v2.0 (p0.001) and 16.0 mL using v2.1 (p0.001). In the presence of an enlarged transition zone the PGV tended to be higher than the reference standard for PI-RADS v2.0 (median difference of 4.7 mL; p = 0.018) and for v2.1 (median difference of 5.7 mL, p0.001) using the ellipsoid formula.Inter-reader agreement was excellent for the calculated PGV for both methods. PI-RADS v2.0 measurements with the ellipsoid formula yielded the most accurate volume estimates. The differences between PI-RADS v2.0 and v2.1 were statistically significant although small in absolute numbers but may be of relevance in specific clinical scenarios like prostate-specific antigen density calculation. These findings validate the use of the ellipsoid formula and highlight that the bullet formula should not be used for prostate volume estimation due to systematic overestimation.

To compare interreader agreement and diagnostic accuracy of LI-RADS v2018 categorization using quantitative versus qualitative MRI assessment of arterial phase hyperenhancement (APHE) and washout (WO) of focal liver lesions. Sixty patients (19 female; mean age, 56 years) at risk for HCC with 71 liver lesions (28 HCCs, 43 benign) who underwent contrast-enhanced MRI were included in this retrospective study. Four blinded radiologists independently assigned a qualitative LI-RADS score per lesion. Two other radiologists placed ROIs within the lesion, adjacent liver parenchyma, and paraspinal musculature on pre- and post-contrast MR images. The percentage of arterial enhancement and the liver-to-lesion contrast ratio were calculated for quantification of APHE and WO. Using these quantitative parameters, a quantitative LI-RADS score was assigned. Interreader agreement and AUCs were calculated. Interreader agreement was similar for qualitative and quantitative LI-RADS (κ = 0.38 vs. 0.40–0.47) with a tendency towards improved agreement for quantitatively assessed APHE (κ = 0.65 vs. 0.81) and WO (κ = 0.53 vs. 0.78). Qualitative LI-RADS showed an AUC of 0.86, 0.94, 0.94, and 0.91 for readers 1, 2, 3, and 4, respectively. The quantitative LI-RADS score where APHE/WO/or both were replaced showed an AUC of 0.89/0.84/0.89, 0.95/0.92/0.92, 0.93/0.91/0.89, and 0.91/0.86/0.88 for readers 1, 2, 3, and 4, respectively. Sensitivity of LR-4/5 slightly increased, while specificity slightly decreased using quantitative APHE. Qualitative and quantitative LI-RADS showed similar performance. Quantitatively assessed APHE showed the potential to increase interreader agreement and sensitivity of HCC diagnosis, whereas quantitatively assessed WO had the opposite effect and needs to be redefined. • Quantitative assessment of arterial phase hyperenhancement shows the potential to increase interreader agreement and sensitivity to diagnose hepatocellular carcinoma. • Adding quantitative measurements of major LI-RADS features does not improve accuracy over qualitative assessment alone according to the LI-RADS v2018 algorithm.

Background Recent studies have reported the additive value of combined gallium 68 (68Ga)-labeled Glu-urea-Lys (Ahx)-HBED-CC ligand targeting the prostate-specific membrane antigen (PSMA) (hereafter called 68Ga-PSMA-11) PET/MRI for the detection and localization of primary prostate cancer compared with multiparametric MRI. Purpose To compare the diagnostic accuracy and interrater agreement of multiparametric MRI and 68Ga-PSMA-11 PET/MRI for the detection of extracapsular extension (ECE) and seminal vesicle infiltration (SVI) in patients with prostate cancer. Materials and Methods Retrospective analysis of 40 consecutive men who underwent multiparametric MRI and 68Ga-PSMA-11 PET/MRI within 6 months for suspected prostate cancer followed by radical prostatectomy between April 2016 and July 2018. Four readers blinded to clinical and histopathologic findings rated the probability of ECE and SVI at multiparametric MRI and PET/MRI by using a five-point Likert-type scale. The prostatectomy specimen served as the reference standard. Accuracy was assessed with a multireader multicase analysis and by calculating reader-average areas under the receiver operating characteristics curve (AUCs), sensitivity, and specificity for ordinal and dichotomized data in a region-specific and patient-specific approach. Interrater agreement was assessed with the Fleiss multirater κ. Results For multiparametric MRI versus PET/MRI in ECE detection, respectively, AUC, sensitivity, and specificity in the region-specific analysis were 0.67 and 0.75 (P = .07), 28% (21 of 76) and 47% (36 of 76) (P = .09), and 94% (529 of 564) and 90% (509 of 564) (P = .007). For the patient-specific analysis, AUC, sensitivity, and specificity were 0.66 and 0.73 (P = .19), 46% (22 of 48) and 69% (33 of 48) (P = .04), and 75% (84 of 112) and 67% (75 of 112) (P = .19), respectively. For multiparametric MRI versus PET/MRI in SVI detection, respectively, AUC, sensitivity, and specificity of the region-specific analysis were 0.66 and 0.74 (P = .21), 35% (seven of 20) and 50% (10 of 20) (P = .25), and 98% (295 of 300) and 94% (282 of 300) (P < .001). For the patient-specific analysis, AUC, sensitivity, and specificity were 0.65 and 0.79 (P = .25), 35% (seven of 20) and 55% (11 of 20) (P = .20), and 98% (137 of 140) and 94% (131 of 140) (P = .07), respectively. Interrater reliability for multiparametric MRI versus PET/MRI did not differ for ECE (κ, 0.46 vs 0.40; P = .24) and SVI (κ, 0.23 vs 0.33; P = .39). Conclusion Our results suggest that gallium 68 (68Ga)-labeled Glu-urea-Lys (Ahx)-HBED-CC ligand targeting the prostate-specific membrane antigen (PSMA) (68Ga-PSMA-11) PET/MRI and multiparametric MRI perform similarly for local staging of prostate cancer in patients with intermediate-to-high-risk prostate cancer. The increased sensitivity of 68Ga-PSMA-11 PET/MRI for the detection of extracapsular disease comes at the cost of a slightly reduced specificity. © RSNA, 2019.

A first analysis of simultaneous 68Ga-prostate-specific membrane antigen (PSMA)-11 PET/MRI showed some improvement in the detection of recurrent disease at low serum prostate specific antigen (PSA) values below 0.5 ng/mL compared with the already high detection rate of 68Ga-PSMA-11 PET/CT. We therefore focused on all patients with biochemical recurrence and PSA values no higher than 0.5 ng/mL to assess the detection rate for 68Ga-PSMA-11 PET/MRI. Methods: We retrospectively analyzed a cohort of 66 consecutive patients who underwent 68Ga-PSMA-11 PET/MRI for biochemical recurrence with a PSA value no higher than 0.5 ng/mL at our institution. Median PSA level was 0.23 ng/mL (range, 0.03-0.5 ng/mL). Detection of PSMA-positive lesions within the prostate fossa, local and distant lymph nodes, bones, or visceral organs was recorded. In addition, all scans with 68Ga-PSMA-11 PET/MRI-positive lesions were retrospectively assessed to analyze if lesions were detected inside or outside a standard salvage radiotherapy volume. Results: Overall, in 36 of 66 patients (54.5%) PSMA-positive lesions were detected; in 26 of 40 (65%) patients with a PSA level between 0.2 and 0.5 ng/mL and in 10 of 26 (38.5%) patients with a PSA level less than 0.2 ng/mL. Even at those low PSA values, only 8 of 66 (12.1%) patients had exclusive local recurrence. Lymph nodes were detected in 23 patients and bone metastases in 5 on 68Ga-PSMA-11 PET/MRI. In 26 of 66 patients (39.4%), PSMA-positive lesions were located outside a standard salvage radiotherapy volume. Conclusion: Our data confirm that 68Ga-PSMA-11 PET/MRI has a high detection rate for recurrent prostate cancer, even at low PSA levels no higher than 0.5 ng/mL. In addition, we show that 68Ga-PSMA-11 PET/MRI detected PSMA-positive lesions outside a standard salvage radiotherapy volume in 39.4% of all patients.

Background Inflammation plays a fundamental role in mediating all stages of atherosclerosis. Given the higher prevalence of inflammatory rheumatologic conditions in women and the female propensity towards worse cardiovascular outcomes, refined strategies are needed to better identify the high-risk female cardiovascular phenotype. Objectives This article aims to assess sex-specific links between inflammatory processes and the development and progression of ischemic heart disease. Patients and Methods The relationship between vertebral bone marrow metabolism—a marker of inflammation—and myocardial injury was retrospectively assessed in 294 patients (28.6% women, mean age: 66.9 ± 10.0 years) who underwent 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) and 99mTc-tetrofosmin single-photon emission computed tomography myocardial perfusion imaging (SPECT-MPI). Results A significant increase in 18F-FDG bone marrow uptake was observed in women with impaired myocardial perfusion (SPECT-MPI) as compared to women with normal myocardial perfusion (standardized uptake value [SUV]: 2.2 ± 1.2 vs. 1.7 ± 0.5, p = 0.013), while no such difference was observed in men (SUV: 1.6 ± 0.8 vs. 1.6 ± 0.4, p = 0.372). Furthermore, a significant inverse correlation between left ventricular ejection fraction (LVEF) and bone marrow metabolism was seen in women (r = –0.229, p = 0.037), but not in men (r = –0.075, p = 0.289). Accordingly, in women, but not in men, bone marrow activity was identified as an independent predictor of both, reduced LVEF (β-coefficient, –4.537; p = 0.040) and impaired myocardial perfusion (β-coefficient, 0.138; p = 0.014). Conclusion A strong link between bone marrow metabolism and impaired myocardial function and perfusion was observed in women, but not in men. Our data suggest that novel biomarkers of inflammation might help to identify women at risk for ischemic cardiomyopathy and to tailor disease management to the female cardiovascular phenotype.

To investigate and compare the reproducibility and accuracy of qualitative ratings and quantitative texture analysis (TA) in detection and grading of lumbar spinal stenosis (LSS) in magnetic resonance imaging (MR) scans of the lumbar spine.From a nationwide multicenter and multidisciplinary lumbar stenosis outcome study (LSOS) register 82 patients, undergoing MR scans of the lumbar spine due to clinical indication of spinal claudication, with a single level central or lateral severe LSS were included. In total 343 transaxial T2-weighted images of the lumbar spine were included from one to five levels (L1 to S1) per patient. One expert radiologist serving as reference standard rated LSS grade according to a standard four-point (normal to severe) as well as to an eight-point Schizas grading scale. DICOM data were then rescaled to a defined pixel size. Two independent readers performed qualitative ratings analogous to expert reader in addition to TA of spinal canals by manually placing two regions of interest (ROI) per image reflecting qualitative scales: (1) dural sac only (2) inner contour of the spinal canal including epidural fat and bilateral recesses. Interreader agreements of qualitative and quantitative parameters were assessed by Cohen's Kappa (κ) and intraclass correlation (ICC), respectively. TA feature reduction was performed by ICC threshold0.75. Remaining features were analyzed with machine learning algorithms (Weka 3 tool) for correlation with LSS grades using 10-fold cross validation.Qualitative ratings showed only moderate reproducibility for both LSS classification systems but high correlation with cut-off cross-sectional area (CSA)130mm² for severe spinal stenosis. In quantitative TA of both ROIs, machine learning analysis with a decision tree classifier revealed higher performances for LSS grading compared to qualitative assessments using the reference CSA cut-off, respectively.Qualitative LSS grading independent of classification system shows moderate reproducibility. TA with machine learning offers highly reproducible quantitative parameters that increase accuracy for severe LSS detection with minor impact of grading score and CSA border definition.

Introduction/Background: Radiographic progression-free survival (rPFS) based on Prostate Cancer Working Group 2 (PCWG2) has been increasingly used as a meaningful imaging-based intermediate endpoint (IBIE) for overall survival (OS) in patients with metastatic castration-resistant prostate cancer (mCRPC). In randomized phase III trials, rPFS showed good correlation with OS at the individual trial level. We aimed to assess the correlation between the hazard ratios (HR) of IBIE and OS among PCWG2-based randomized trials. Materials and Methods: Pubmed and EMBASE databases were systematically searched for randomized trials evaluating systemic treatments on mCRPC using PCWG2 up to April 15, 2020. Hazard ratios for OS and IBIEs were extracted and their correlation was assessed using weighted linear regression. Subgroup analyses were performed according to various clinical settings: prior chemotherapy, drug category, type of IBIE (rPFS vs composite IBIE, latter defined as progression by imaging and one or a combination of PSA, pain, skeletal-related events, and performance status), and publication year. Results: Twenty-eight phase II-III randomized trials (16,511 patients) were included. Correlation between OS and IBIE was good (R2=0.57, 95%CI 0.35–0.78). Trials using rPFS showed substantially higher correlation than those using a composite IBIE (R2=0.58, 95%CI 0.32–0.82 vs 0.00, 95%CI -0.01–0.01). Correlations between OS and IBIE in other subgroups were at least moderate in nearly all subgroups (R2=0.32–0.91). Conclusion: IBIEs in the era of PCWG2 correlate well with OS in randomized trials for systemic drugs in patients with mCRPC. PCWG2-based rPFS should be used instead of a composite IBIE that includes PSA and other clinical variables.

Background Positron emission tomography (PET) targeting the prostate-specific membrane antigen (PSMA) has superior sensitivity over conventional imaging (CI) to stage prostate cancer (PCa) and therefore is increasingly used in staging to stratify patients before radical therapy. Whether this improved diagnostic accuracy translates into improved outcome after radical prostatectomy (RPE) has not yet been shown. Therefore, the aim of this study was to compare the oncological outcome after RPE between patients that underwent preoperative staging with CI or PSMA-PET for intermediate and high-risk PCa. Methods We retrospectively selected all patients that underwent RPE for intermediate- or high-risk PCa at our institution before PSMA-PET introduction (between March 2014 and September 2016) and compared the oncologic outcome of patients staged with PSMA-PET (between October 2016 and October 2018). Oncological pre-surgical risk parameters (age, PSA, D’Amico score, biopsy-ISUP, and cT stage) were compared between the groups. Oncological outcome was determined as PSA persistence, nerve-sparing rate, and surgical margin status. Wilcoxon rank-sum, Fisher’s, and chi-square tests where used for statistical testing. Results One hundred five patients were included, 53 in the CI group and 52 in the PSMA-group. Patients in the PSMA group had higher ISUP grade (p p p = 0.15 and 0.13, respectively). Subgroup analysis with high-risk patients revealed PSA persistence in 7% (3/44) in the PSMA group and 25% (7/28) in the CI group (p = 0.04). Limitations include the retrospective design and choline-PET for some patients in the CI group. Conclusion Immediate outcome after RPE was not worse in the PSMA group compared with the CI group, despite a higher-risk cohort. In a comparison of only high-risk patients, PSMA-PET staging was associated with a significantly lower rate of postsurgical PSA persistence.

Bone regeneration is a complex process and the clinical translation of tissue engineered constructs (TECs) remains a challenge. The combination of biomaterials and mesenchymal stem cells (MSCs) may enhance the healing process through paracrine effects. Here, we investigated the influence of cell format in combination with a collagen scaffold on key factors in bone healing process, such as mineralization, cell infiltration, vascularization, and ECM production. MSCs as single cells (2D-SCs), assembled into microtissues (3D-MTs) or their corresponding secretomes were combined with a collagen scaffold and incubated on the chicken embryo chorioallantoic membrane (CAM) for 7 days. A comprehensive quantitative analysis was performed on a cellular level by histology and by microcomputed tomography (microCT). In all experimental groups, accumulation of collagen and glycosaminoglycan within the scaffold was observed over time. A pronounced cell infiltration and vascularization from the interface to the surface region of the CAM was detected. The 3D-MT secretome showed a significant mineralization of the biomaterial using microCT compared to all other conditions. Furthermore, it revealed a homogeneous distribution pattern of mineralization deposits in contrast to the cell-based scaffolds, where mineralization was only at the surface. Therefore, the secretome of MSCs assembled into 3D-MTs may represent an interesting therapeutic strategy for a next-generation bone healing concept., Scientific Reports, 11 (1), ISSN:2045-2322

Purpose The aim of this study was to evaluate the use of a Bayesian penalized likelihood reconstruction algorithm (Q.Clear) for 89Zr-immunoPET image reconstruction and its potential to improve image quality and reduce the administered activity of 89Zr-immunoPET tracers. Methods Eight 89Zr-immunoPET whole-body PET/CT scans from three 89Zr-immunoPET clinical trials were selected for analysis. On average, patients were imaged 6.3 days (range 5.0–8.0 days) after administration of 69 MBq (range 65–76 MBq) of [89Zr]Zr-DFO-daratumumab, [89Zr]Zr-DFO-pertuzumab, or [89Zr]Zr-DFO-trastuzumab. List-mode PET data was retrospectively reconstructed using Q.Clear with incremental β-values from 150 to 7200, as well as standard ordered-subset expectation maximization (OSEM) reconstruction (2-iterations, 16-subsets, a 6.4-mm Gaussian transaxial filter, “heavy” z-axis filtering and all manufacturers’ corrections active). Reduced activities were simulated by discarding 50% and 75% of original counts in each list mode stream. All reconstructed PET images were scored for image quality and lesion detectability using a 5-point scale. SUVmax for normal liver and sites of disease and liver signal-to-noise ratio were measured. Results Q.Clear reconstructions with β = 3600 provided the highest scores for image quality. Images reconstructed with β-values of 3600 or 5200 using only 50% or 25% of the original counts provided comparable or better image quality scores than standard OSEM reconstruction images using 100% of counts. Conclusion The Bayesian penalized likelihood reconstruction algorithm Q.Clear improved the quality of 89Zr-immunoPET images. This could be used in future studies to improve image quality and/or decrease the administered activity of 89Zr-immunoPET tracers.

Human brown adipose tissue (BAT) is a thermogenic tissue activated by the sympathetic nervous system in response to cold exposure. It contributes to energy expenditure (EE) and takes up glucose and lipids from the circulation. Studies in rodents suggest that BAT contributes to the transient rise in EE after food intake, so-called diet-induced thermogenesis (DIT). We investigated the relationship between human BAT activity and DIT in response to glucose intake in 17 healthy volunteers. We assessed DIT, cold-induced thermogenesis (CIT), and maximum BAT activity at three separate study visits within 2 wk. DIT was measured by indirect calorimetry during an oral glucose tolerance test. CIT was assessed as the difference in EE after cold exposure of 2-h duration as compared with warm conditions. Maximal activity of BAT was assessed by 18-F-fluoro-deoxyglucose (18F-FDG) 18F-FDG-PET/MRI after cold exposure and concomitant pharmacological stimulation with mirabegron. Seventeen healthy men (mean age = 23.4 yr, mean body mass index = 23.2 kg/m2) participated in the study. EE increased from 1,908 (±181) kcal/24 h to 2,128 (±277) kcal/24 h (P < 0.0001, +11.5%) after mild cold exposure. An oral glucose load increased EE from 1,911 (±165) kcal/24 h to 2,096 (±167) kcal/24 h at 60 min (P < 0.0001, +9.7%). The increase in EE in response to cold was significantly associated with BAT activity (R2 = 0.43, P = 0.004). However, DIT was not associated with BAT activity (R2 = 0.015, P = 0.64). DIT after an oral glucose load was not associated with stimulated 18F-FDG uptake into BAT, suggesting that DIT is independent from BAT activity in humans (Clinicaltrials.gov Registration No. NCT03189511).NEW & NOTEWORTHY Cold-induced thermogenesis (CIT) was related to BAT activity as determined by FDG-PET/MRI after stimulation of BAT. Diet-induced thermogenesis (DIT) was not related to stimulated BAT activity. Supraclavicular skin temperature was related to CIT but not to DIT. DIT in humans is probably not a function of BAT.

Thyroid hormone (TH) is an important regulator of mammalian metabolism and facilitates cold induced thermogenesis (CIT) in brown adipose tissue (BAT). Profound hypothyroidism or hyperthyroidism lead to alterations in BAT function and CIT. In euthyroid humans the inter-individual variation of thyroid hormones is relatively large. Therefore, we investigated whether levels of free thyroxine (T4) or free triiodothyronine (T3) are positively associated with CIT in euthyroid individuals. We performed an observational study in 79 healthy, euthyroid volunteers (mean age 25.6 years, mean BMI 23.0 kg · m-2). Resting energy expenditure (REE) was measured by indirect calorimetry during warm conditions (EEwarm) and after a mild cold stimulus of two hours (EEcold). CIT was calculated as the difference between EEcold and EEwarm. BAT activity was assessed by 18F-FDG-PET after a mild cold stimulus in a subset of 26 participants. EEcold and CIT were significantly related to levels of free T4 (R2 = 0.11, p=0.0025 and R2 = 0.13, p=0.0011, respectively) but not to free T3 and TSH. Cold induced BAT activity was also associated with levels of free T4 (R2 = 0.21, p=0.018). CIT was approximately fourfold higher in participants in the highest tertile of free T4 as compared to the lowest tertile. Additionally, free T4 was weakly, albeit significantly associated with outdoor temperature seven days prior to the respective study visit (R2 = 0.06, p=0.037). These finding suggests that variations in thyroid hormone levels within the euthyroid range are related to the capability to adapt to cool temperatures and affect energy balance., Frontiers in Endocrinology, 12, ISSN:1664-2392

Highlights • Image quality is similar for different body phased-array receive coil setups. • An 18-channel body phased-array receive coil setup achieved good image quality. • 60-channel body phased-array receive coil setup slightly improves SNR in T2W images., Purpose To evaluate the influence of body phased-array (BPA) receive coil setups on signal-to-noise ratio (SNR) and image quality (IQ) in prostate MRI. Methods This prospective study evaluated axial T2-weighted images (T2W-TSE) and DWI of the prostate in ten healthy volunteers with 18-channel (18CH), 30-channel and 60-channel (60CH) BPA receive coil setups. SNR and ADC values were assessed in the peripheral and transition zones (TZ). Two radiologists rated IQ features. Differences in qualitative and quantitative image features between BPA receive coil setups were compared. After correction for multiple comparisons, p-values

Purpose The aim of this study was to evaluate the use of a Bayesian penalized likelihood reconstruction algorithm (Q.Clear) for 89Zr-immunoPET image reconstruction and its potential to improve image quality and reduce the administered activity of 89Zr-immunoPET tracers. Methods Eight 89Zr-immunoPET whole-body PET/CT scans from three 89Zr-immunoPET clinical trials were selected for analysis. On average, patients were imaged 6.3 days (range 5.0–8.0 days) after administration of 69 MBq (range 65–76 MBq) of [89Zr]Zr-DFO-daratumumab, [89Zr]Zr-DFO-pertuzumab, or [89Zr]Zr-DFO-trastuzumab. List-mode PET data was retrospectively reconstructed using Q.Clear with incremental β-values from 150 to 7200, as well as standard ordered-subset expectation maximization (OSEM) reconstruction (2-iterations, 16-subsets, a 6.4-mm Gaussian transaxial filter, “heavy” z-axis filtering and all manufacturers’ corrections active). Reduced activities were simulated by discarding 50% and 75% of original counts in each list mode stream. All reconstructed PET images were scored for image quality and lesion detectability using a 5-point scale. SUVmax for normal liver and sites of disease and liver signal-to-noise ratio were measured. Results Q.Clear reconstructions with β = 3600 provided the highest scores for image quality. Images reconstructed with β-values of 3600 or 5200 using only 50% or 25% of the original counts provided comparable or better image quality scores than standard OSEM reconstruction images using 100% of counts. Conclusion The Bayesian penalized likelihood reconstruction algorithm Q.Clear improved the quality of 89Zr-immunoPET images. This could be used in future studies to improve image quality and/or decrease the administered activity of 89Zr-immunoPET tracers. Supplementary Information The online version contains supplementary material available at 10.1186/s40658-021-00352-z.

Purpose Prostate-specific membrane antigen positron emission tomography (PSMA-PET) has shown promise for detecting nodal and distant prostate cancer (PCa) metastases. However, its performance for local tumor staging is not as well established. The purpose of this study was to review the diagnostic performance of PSMA-PET for determining seminal vesical invasion (SVI) and extraprostatic extension (EPE). Methods Pubmed and Embase databases were searched until January 12, 2020. Studies assessing accuracy of PSMA-PET in determining SVI and EPE were included. Study quality was evaluated with the revised Quality Assessment of Diagnostic Accuracy Studies-2 tool. Pooled sensitivity and specificity were calculated using hierarchical summary receiver operating characteristics modeling. Heterogeneity was explored using meta-regression analyses for anatomical imaging component (MRI vs CT) and by testing for a threshold effect. Results Twelve studies (615 patients) were included. Pooled sensitivity and specificity were 0.68 (95% CI 0.53-0.81) and 0.94 (95% CI 0.90-0.96) for SVI and 0.72 (95% CI 0.56-0.84) and 0.87 (95% CI 0.72-0.94) for EPE. Meta-regression analyses showed that for SVI, PET/MRI demonstrated greater sensitivity than PET/CT (0.87 [95% CI 0.75-0.98] vs 0.60 [95% CI 0.47-0.74]; p = 0.02 for joint model) while specificity was comparable (0.91 [95% CI 0.84-0.97] vs. 0.96 [95% CI 0.93-0.99]) but not for EPE (p = 0.08). A threshold effect was present for studies assessing EPE (correlation coefficient = 0.563 [95% CI, −0.234-0.908] between sensitivity and false-positive rate). Conclusion PSMA-PET has moderate sensitivity and excellent specificity for assessing local tumor extent in patients with PCa. PET/MRI showed potential for greater sensitivity than PET/CT in assessing SVI.

For clinically significant, locally confined prostate cancer, whole-gland radical prostatectomy and radiotherapy are established effective treatment strategies that, however, come at a cost of significant morbidity related to urinary and sexual side effects. The concept of risk stratification paired with a better understanding of prognostic factors has led to the development of alternative management options including active surveillance and focal therapy for appropriately selected patients with localized disease. High-intensity focused ultrasound (HIFU) is one such minimally invasive, image-guided treatment option for prostate cancer. Due to the relative novelty of HIFU and the increased use of magnetic resonance imaging in prostate cancer, many radiologists are not yet familiar with imaging findings related to HIFU, their temporal evolution as well as imaging appearance of recurrent disease after this type of focal therapy. HIFU induces sharply demarcated, localized coagulative necrosis of a tumor through thermal energy delivered via an endorectal or transurethral ultrasound transducer. In this pictorial review, we aim at providing relevant background information that will guide the reader through the general principles of HIFU in the prostate, as well as demonstrate the imaging appearance of expected post-HIFU changes versus recurrent tumor.