Feasibility and performance of spin-echo EPI MR elastography at 3 Tesla for staging hepatic fibrosis in the presence of hepatic iron overload.

PURPOSE: To assess the feasibility and performance of MR elastography (MRE) for quantifying liver fibrosis in patients with and without hepatic iron overload. METHODS: This retrospective single-center study analyzed 139 patients who underwent liver MRI at 3 Tesla including MRE (2D spin-echo EPI sequence) and R2* mapping for liver iron content (LIC) estimation. MRE feasibility and diagnostic performance between patients with normal and elevated LIC were compared. RESULTS: Patients with elevated LIC (21%) had significantly higher MRE failure rates (24.1% vs. 3.6%, p < 0.001) compared to patients with normal LIC (79%). For those with only insignificant to mild iron overload (LIC < 5.4 mg/g; 17%), MRE failure rate did not differ significantly from patients without iron overload (8.3% vs. 3.6%, p = 0.315). R2* predicted MRE failure with fair accuracy at a threshold of R2* ≥ 269 s-1 (LIC of approximately 4.6 mg/g). MRE showed good diagnostic performance for detecting significant (≥ F2) and severe fibrosis (≥ F3) in patients without (AUC 0.835 and 0.900) and with iron overload (AUC 0.818 and 0.889) without significant difference between the cohorts (p = 0.884 and p = 0.913). For detecting cirrhosis MRE showed an excellent diagnostic performance in both groups (AUC 0.944 and 1.000, p = 0.009). CONCLUSION: Spin-echo EPI MRE at 3 Tesla is feasible in patients with mild iron overload with good to excellent performance for detecting hepatic fibrosis with a failure rate comparable to patients without iron overload.

Early post-treatment MRI predicts long-term hepatocellular carcinoma response to radiation segmentectomy.

OBJECTIVES: Radiation segmentectomy using yttrium-90 plays an emerging role in the management of early-stage HCC. However, the value of early post-treatment MRI for response assessment is uncertain. We assessed the value of response criteria obtained early after radiation segmentectomy in predicting long-term response in patients with HCC. MATERIALS AND METHODS: Patients with HCC who underwent contrast-enhanced MRI before, early, and 12 months after radiation segmentectomy were included in this retrospective single-center study. Three independent radiologists reviewed images at baseline and 1st follow-up after radiation segmentectomy and assessed lesion-based response according to mRECIST, LI-RADS treatment response algorithm (TRA), and image subtraction. The endpoint was response at 12 months based on consensus readout of two separate radiologists. Diagnostic accuracy for predicting complete response (CR) at 12 months based on the 1st post-treatment MRI was calculated. RESULTS: Eighty patients (M/F 60/20, mean age 67.7 years) with 80 HCCs were assessed (median size baseline, 1.8 cm [IQR, 1.4-2.9 cm]). At 12 months, 74 patients were classified as CR (92.5%), 5 as partial response (6.3%), and 1 as progressive disease (1.2%). Diagnostic accuracy for predicting CR was fair to good for all readers with excellent positive predictive value (PPV): mRECIST (range between 3 readers, accuracy: 0.763-0.825, PPV: 0.966-1), LI-RADS TRA (accuracy: 0.700-0.825, PPV: 0.983-1), and subtraction (accuracy: 0.775-0.825, PPV: 0.967-1), with no difference in accuracy between criteria (p range 0.053 to > 0.9). CONCLUSION: mRECIST, LI-RADS TRA, and subtraction obtained on early post-treatment MRI show similar performance for predicting long-term response in patients with HCC treated with radiation segmentectomy. CLINICAL RELEVANCE STATEMENT: Response assessment extracted from early post-treatment MRI after radiation segmentectomy predicts complete response in patients with HCC with high PPV (≥ 0.96). KEY POINTS: • Early post-treatment response assessment on MRI predicts response in patients with HCC treated with radiation segmentectomy with fair to good accuracy and excellent positive predictive value. • There was no difference in diagnostic accuracy between mRECIST, LI-RADS, and subtraction for predicting HCC response to radiation segmentectomy.

Immune-Related Sclerosing Cholangitis and Subsequent Pyogenic Liver Abscesses in Two Patients With Melanoma Treated by Triplet Therapy: A Case Report.

Immune checkpoint inhibitors have improved the treatment of many cancers. However, immune-related (IR) adverse events can limit their use. A rare but potentially severe IR adverse event is IR-cholangitis, which is mostly induced by anti-programmed cell death 1 (PD1) antibodies and is often corticosteroid-resistant. Consequently, immunosuppressive therapy is increased, which interferes with the antitumor response and bears the risk of infection. We report on 2 patients with BRAF V600E mutant melanoma, who presented with IR-sclerosing cholangitis under triplet therapy with atezolizumab [anti-programmed cell death ligand 1 (PD-L1) antibody], vemurafenib (BRAF inhibitor), and cobimetinib (MEK inhibitor). In both cases, the administration of corticosteroids initially resulted in a marginal improvement but was followed by a rebound of biliary enzymes and the subsequent emergence of pyogenic liver abscesses with bacteremia. Liver abscesses developed without preceding invasive procedures, which implies that a more restrictive approach to immunosuppressive therapy for IR-cholangitis should be considered. To our knowledge, we report the first 2 cases of IR-cholangitis and subsequent liver abscesses without prior invasive intervention, the first cases of IR-cholangitis induced by triplet therapy, and 2 of the few anti-PD-L1 induced cases contributing to the evidence that both anti-PD1 and anti-PD-L1 antibodies induce IR-cholangitis. Treatment strategies for IR-cholangitis need to be improved to prevent life-threatening infectious complications.

Early Prediction of Response of Hepatocellular Carcinoma to Yttrium-90 Radiation Segmentectomy Using a Machine Learning MR Imaging Radiomic Approach.

PURPOSE: To assess the accuracy of a machine learning (ML) approach based on magnetic resonance (MR) imaging radiomic quantification obtained before treatment and early after treatment for prediction of early hepatocellular carcinoma (HCC) response to yttrium-90 transarterial radioembolization (TARE). MATERIALS AND METHODS: In this retrospective single-center study of 76 patients with HCC, baseline and early (1-2 months) post-TARE MR images were collected. Semiautomated tumor segmentation facilitated extraction of shape, first-order histogram, and custom signal intensity-based radiomic features, which were then trained (n = 46) using a ML XGBoost model and validated on a separate cohort (n = 30) not used in training to predict treatment response assessed at 4-6 months (based on modified Response and Evaluation Criteria in Solid Tumors criteria). Performance of this ML radiomic model was compared with those of models comprising clinical parameters and standard imaging characteristics using area under the receiver operating curve (AUROC) analysis for prediction of complete response (CR). RESULTS: Seventy-six tumors with a mean (±SD) diameter of 2.6 cm ± 1.6 were included. Sixty, 12, 1, and 3 patients were classified as having CR, partial response, stable disease, and progressive disease, respectively, at 4-6 months posttreatment on the basis of MR images. In the validation cohort, the radiomic model showed good performance (AUROC, 0.89) for prediction of CR, compared with models comprising clinical and standard imaging criteria (AUROC, 0.58 and 0.59, respectively). Baseline imaging features appeared to be more heavily weighted in the radiomic model. CONCLUSIONS: The use of ML modeling of radiomic data combining baseline and early follow-up MR imaging could predict HCC response to TARE. These models need to be investigated further in an independent cohort.

Semiautomated segmentation of hepatocellular carcinoma tumors with MRI using convolutional neural networks.

OBJECTIVE: To assess the performance of convolutional neural networks (CNNs) for semiautomated segmentation of hepatocellular carcinoma (HCC) tumors on MRI. METHODS: This retrospective single-center study included 292 patients (237 M/55F, mean age 61 years) with pathologically confirmed HCC between 08/2015 and 06/2019 and who underwent MRI before surgery. The dataset was randomly divided into training (n = 195), validation (n = 66), and test sets (n = 31). Volumes of interest (VOIs) were manually placed on index lesions by 3 independent radiologists on different sequences (T2-weighted imaging [WI], T1WI pre-and post-contrast on arterial [AP], portal venous [PVP], delayed [DP, 3 min post-contrast] and hepatobiliary phases [HBP, when using gadoxetate], and diffusion-weighted imaging [DWI]). Manual segmentation was used as ground truth to train and validate a CNN-based pipeline. For semiautomated segmentation of tumors, we selected a random pixel inside the VOI, and the CNN provided two outputs: single slice and volumetric outputs. Segmentation performance and inter-observer agreement were analyzed using the 3D Dice similarity coefficient (DSC). RESULTS: A total of 261 HCCs were segmented on the training/validation sets, and 31 on the test set. The median lesion size was 3.0 cm (IQR 2.0-5.2 cm). Mean DSC (test set) varied depending on the MRI sequence with a range between 0.442 (ADC) and 0.778 (high b-value DWI) for single-slice segmentation; and between 0.305 (ADC) and 0.667 (T1WI pre) for volumetric-segmentation. Comparison between the two models showed better performance in single-slice segmentation, with statistical significance on T2WI, T1WI-PVP, DWI, and ADC. Inter-observer reproducibility of segmentation analysis showed a mean DSC of 0.71 in lesions between 1 and 2 cm, 0.85 in lesions between 2 and 5 cm, and 0.82 in lesions > 5 cm. CONCLUSION: CNN models have fair to good performance for semiautomated HCC segmentation, depending on the sequence and tumor size, with better performance for the single-slice approach. Refinement of volumetric approaches is needed in future studies. KEY POINTS: • Semiautomated single-slice and volumetric segmentation using convolutional neural networks (CNNs) models provided fair to good performance for hepatocellular carcinoma segmentation on MRI. • CNN models' performance for HCC segmentation accuracy depends on the MRI sequence and tumor size, with the best results on diffusion-weighted imaging and T1-weighted imaging pre-contrast, and for larger lesions.

Index lesion contouring on prostate MRI for targeted MRI/US fusion biopsy - Evaluation of mismatch between radiologists and urologists.

PURPOSE: Mistargeting of focal lesions due to inaccurate segmentations can lead to false-negative findings on MRI-guided targeted biopsies. The purpose of this retrospective study was to examine inter-reader agreement of prostate index lesion segmentations from actual biopsy data between urologists and radiologists. METHOD: Consecutive patients undergoing transperineal MRI-targeted prostate biopsy for PI-RADS 3-5 lesions between January 2020 and December 2021 were included. Agreement between segmentations on T2w-images between urologists and radiologists was assessed with Dice similarity coefficient (DSC) and 95 % Hausdorff distance (95 % HD). Differences in similarity scores were compared using Wilcoxon test. Differences depending on lesion features (size, zonal location, PI-RADS scores, lesion distinctness) were tested with Mann-Whitney U test. Correlation with prostate signal-intensity homogeneity score (PSHS) and lesion size was tested with Spearman's rank correlation. RESULTS: Ninety-three patients (mean age 64.9 ± 7.1y, median serum PSA 6.5 [4.33-10.00]) were included. Mean similarity scores were statistically significantly lower between urologists and radiologists compared to radiologists only (DSC 0.41 ± 0.24 vs. 0.59 ± 0.23, p < 0.01; 95 %HD 6.38 ± 5.45 mm vs. 4.47 ± 4.12 mm, p < 0.01). There was a moderate and strong positive correlation between DSC scores and lesion size for segmentations from urologists and radiologists (ρ = 0.331, p = 0.002) and radiologists only (ρ = 0.501, p < 0.001). Similarity scores were worse in lesions ≤ 10 mm while other lesion features did not significantly influence similarity scores. CONCLUSION: There is significant mismatch of prostate index lesion segmentations between urologists and radiologists. Segmentation agreement positively correlates with lesion size. PI-RADS scores, zonal location, lesion distinctness, and PSHS show no significant impact on segmentation agreement. These findings could underpin benefits of perilesional biopsies.

Multi-reader evaluation of different image quality scoring systems in prostate MRI.

OBJECTIVES: To evaluate different image quality scoring systems in the assessment of factors limiting diagnostic accuracy of prostate MRI. METHODS: This retrospective IRB-approved study included 281 patients undergoing prostate MRI prior to biopsy. Four readers (2 experienced, 2 novice) independently reviewed all MRI examinations (n = 295) and assigned scores for subjective image quality (1-5; 1:poor, 5:excellent), the PI-QUAL and the PSHS scoring system. The original PI-RADS scores were extracted from the report and transperineal template saturation biopsy served as histopathological reference. RESULTS: Inter-reader agreement was found to be good, with PSHS showing highest agreement (kappa: 0.65). The PSHS scoring system performed well assessing the influence of image quality on sensitivity of MR for clinically-significant cancer for the experienced readers using a PI-RADS score cut-off ≥ 3/≥4, as did the PI-QUAL scoring system with a PI-RADS cut-off ≥ 4. For the less experienced radiologist, this was true for PSHS (clinically-significant and all cancers) and PI-QUAL scores (clinically-significant cancers) for a PI-RADS score ≥ 3. PSHS scores were positively associated with the detection of clinically-significant cancer based on a PI-RADS cut-off ≥ 4, OR 1.86 (95 % CI 1.22-2.82), and had the highest Somers' D. CONCLUSIONS: The PSHS scoring system performed well in assessing the effect of image quality on detection rates, as did the PI-QUAL system. Since both systems focus on different aspects of image quality, their incorporation into prostate MRI reports could further enhance standardization and allow for a reliable assessment of image quality as a potential confounder in prostate MRI.

4D flow MRI in abdominal vessels: prospective comparison of k-t accelerated free breathing acquisition to standard respiratory navigator gated acquisition.

Volumetric phase-contrast magnetic resonance imaging with three-dimensional velocity encoding (4D flow MRI) has shown utility as a non-invasive tool to examine altered blood flow in chronic liver disease. Novel 4D flow MRI pulse sequences with spatio-temporal acceleration can mitigate the long acquisition times of standard 4D flow MRI, which are an impediment to clinical adoption. The purpose of our study was to demonstrate feasibility of a free-breathing, spatio-temporal (k-t) accelerated 4D flow MRI acquisition for flow quantification in abdominal vessels and to compare its image quality, flow quantification and inter-observer reproducibility with a standard respiratory navigator-gated 4D flow MRI acquisition. Ten prospectively enrolled patients (M/F: 7/3, mean age = 58y) with suspected portal hypertension underwent both 4D flow MRI acquisitions. The k-t accelerated acquisition was approximately three times faster (3:11 min ± 0:12 min/9:17 min ± 1:41 min, p < 0.001) than the standard respiratory-triggered acquisition. Vessel identification agreement was substantial between acquisitions and observers. Average flow had substantial inter-sequence agreement in the portal vein and aorta (CV < 15%) and poorer agreement in hepatic and splenic arteries (CV = 11-38%). The k-t accelerated acquisition recorded reduced velocities in small arteries and reduced splenic vein flow. Respiratory gating combined with increased acceleration and spatial resolution are needed to improve flow measurements in these vessels.

Quantitative chest computed tomography combined with plasma cytokines predict outcomes in COVID-19 patients.

Despite extraordinary international efforts to dampen the spread and understand the mechanisms behind SARS-CoV-2 infections, accessible predictive biomarkers directly applicable in the clinic are yet to be discovered. Recent studies have revealed that diverse types of assays bear limited predictive power for COVID-19 outcomes. Here, we harness the predictive power of chest computed tomography (CT) in combination with plasma cytokines using a machine learning and k-fold cross-validation approach for predicting death during hospitalization and maximum severity degree in COVID-19 patients. Patients (n = 152) from the Mount Sinai Health System in New York with plasma cytokine assessment and a chest CT within five days from admission were included. Demographics, clinical, and laboratory variables, including plasma cytokines (IL-6, IL-8, and TNF-α), were collected from the electronic medical record. We found that CT quantitative alone was better at predicting severity (AUC 0.81) than death (AUC 0.70), while cytokine measurements alone better-predicted death (AUC 0.70) compared to severity (AUC 0.66). When combined, chest CT and plasma cytokines were good predictors of death (AUC 0.78) and maximum severity (AUC 0.82). Finally, we provide a simple scoring system (nomogram) using plasma IL-6, IL-8, TNF-α, ground-glass opacities (GGO) to aerated lung ratio and age as new metrics that may be used to monitor patients upon hospitalization and help physicians make critical decisions and considerations for patients at high risk of death for COVID-19.

Imaging features of COVID-19-associated secondary sclerosing cholangitis on magnetic resonance cholangiopancreatography: a retrospective analysis.

BACKGROUND: Despite emerging reports of secondary sclerosing cholangitis (SSC) in critically ill COVID-19 patients little is known about its imaging findings. It presents as delayed progressive cholestatic liver injury with risk of progression to cirrhosis. Diagnosis cannot be made based on clinical presentation and laboratory markers alone. Magnetic resonance imaging (MRI) and magnetic resonance cholangiopancreatography (MRCP) can aid in the diagnosis. The aim of this study was to describe MRI/MRCP imaging features of COVID-19-associated SSC. RESULTS: Seventeen patients (mean age 60.5 years, 15 male) who underwent MRI/MRCP were included. All had been admitted to intensive care unit (ICU) (median duration of ICU stay 10 weeks, range, 2-28 weeks) and developed acute respiratory distress syndrome requiring mechanical ventilation. On imaging, all patients had intrahepatic bile duct strictures and 10 (58.8%) had associated upstream dilatation. Intrahepatic bile duct beading was seen in 14 cases (82.3%). Only one patient (5.9%) had extrahepatic bile duct stricturing. Patchy arterial phase hyperenhancement and high signal on T2- and diffusion-weighted images were seen in 7 cases (53.8%) and 9 cases (52.9%), respectively. Biliary casts were seen in 2 cases (11.8%). Periportal lymphadenopathy and vascular complications were not seen. CONCLUSION: On MRI/MRCP, COVID-19-associated SSC presents with multiple intrahepatic bile duct strictures with or without upstream dilatation and intrahepatic bile duct beading. Surrounding hepatic parenchymal changes including alterations in enhancement and T2 signal are common. The extrahepatic biliary tree was typically spared and periportal lymphadenopathy was missing in all patients.

MR elastography outperforms shear wave elastography for the diagnosis of clinically significant portal hypertension.

OBJECTIVES: Portal hypertension (PH) is associated with complications such as ascites and esophageal varices and is typically diagnosed through invasive hepatic venous pressure gradient (HVPG) measurement, which is not widely available. In this study, we aim to assess the diagnostic performance of 2D/3D MR elastography (MRE) and shear wave elastography (SWE) measures of liver and spleen stiffness (LS and SS) and spleen volume, to noninvasively diagnose clinically significant portal hypertension (CSPH) using HVPG measurement as the reference. METHODS: In this prospective study, patients with liver disease underwent 2D/3D MRE and SWE of the liver and spleen, as well as HVPG measurement. The correlation between MRE/SWE measures of LS/SS and spleen volume with HVPG was assessed. ROC analysis was used to determine the utility of MRE, SWE, and spleen volume for diagnosing CSPH. RESULTS: Thirty-six patients (M/F 22/14, mean age 55 ± 14 years) were included. Of the evaluated parameters, 3D MRE SS had the strongest correlation with HVPG (r = 0.686, p < 0.001), followed by 2D MRE SS (r = 0.476, p = 0.004). 3D MRE SS displayed the best performance for diagnosis of CSPH (AUC = 0.911) followed by 2D MRE SS (AUC = 0.845) and 3D MRE LS (AUC = 0.804). SWE SS showed poor performance for diagnosis of CSPH (AUC = 0.583) while spleen volume was a fair predictor (AUC = 0.738). 3D MRE SS was significantly superior to SWE LS/SS (p ≤ 0.021) for the diagnosis of CSPH. CONCLUSION: SS measured with 3D MRE outperforms SWE for the diagnosis of CSPH. SS appears to be a useful biomarker for assessing PH severity. These results need further validation. KEY POINTS: • Spleen stiffness measured with 2D and 3D MR elastography correlates significantly with hepatic venous pressure gradient measurement. • Spleen stiffness measured with 3D MR elastography demonstrates excellent performance for the diagnosis of clinically significant portal hypertension (AUC 0.911). • Spleen stiffness measured with 3D MR elastography outperforms liver and spleen stiffness measured with shear wave elastography for diagnosis of clinically significant portal hypertension.

Evaluation of a structured treatment discontinuation in patients with inoperable alveolar echinococcosis on long-term benzimidazole therapy: A retrospective cohort study.

OBJECTIVES: Alveolar echinococcosis (AE) is an orphan zoonosis of increasing concern in endemic areas, including Europe. It frequently presents in an advanced, inoperable stage, that requires life-long parasitostatic benzimidazole therapy. In some patients, long-term therapy leads to negative anti-Em18 antibody ELISA and PET. It is disputed, whether these patients are truly cured and treatment can be safely discontinued. Our aim was to retrospectively assess long-term outcome of 34 patients with inoperable AE who participated in a previous study to determine feasibility of benzimidazole treatment cessation. METHODS: Retrospective analysis of medical charts was undertaken in all 34 AE patients who participated in our previous study. Of particular interest were AE recurrence or other reasons for re-treatment in patients who stopped benzimidazole therapy and whether baseline clinical and laboratory parameters help identify of patients that might qualifiy for treatment cessation. Additionally, volumetric measurement of AE lesions on contrast-enhanced cross-sectional imaging was performed at baseline and last follow-up in order to quantify treatment response. RESULTS: 12 of 34 patients stopped benzimidazole therapy for a median of 131 months. 11 of these patients showed stable or regressive AE lesions as determined by volumetric measurement. One patient developed progressive lesions with persistently negative anti-Em18 antibody ELISA but slight FDG-uptake in repeated PET imaging. At baseline, patients who met criteria for treatment cessation demonstrated higher lymphocyte count and lower total IgE. CONCLUSION: Treatment cessation is feasible in inoperable AE patients, who demonstrate negative anti-Em18 antibody ELISA and PET on follow-up. Close monitoring including sectional imaging is strongly advised.

Comparative assessment of standard and immune response criteria for evaluation of response to PD-1 monotherapy in unresectable HCC.

PURPOSE: To assess response to programmed death-1 (PD-1) monotherapy (nivolumab) in hepatocellular carcinoma (HCC) patients using RECIST1.1, modified RECIST (mRECIST), and immune RECIST (iRECIST). A secondary objective was to identify clinicolaboratory and imaging variables predictive of progressive disease (PD) and overall survival (OS). METHODS: Patients with HCC treated with nivolumab at a single institution from 5/2016 to 12/2019 with MRI or CT performed ≥ 4 weeks post treatment were retrospectively assessed. Patients who received concurrent locoregional, radiation, or other systemic therapies were excluded. Response was assessed by 2 observers in consensus using RECIST1.1, mRECIST, and iRECIST at 3/6/9/12-month time points. Time to progression (TTP) and OS were recorded. Clinicolaboratory and imaging variables were evaluated as predictors of PD and OS using uni-/multivariable and Cox regression analyses. RESULTS: Fifty-eight patients (42M/16F) were included. 118 target lesions (TL) were identified before treatment. Baseline mean TL size was 49.1 ± 43.5 mm (range 10-189 mm) for RECIST1.1/iRECIST and 46.3 ± 42.3 mm (range 10-189 mm) for mRECIST. Objective response rate (ORR) was 21% for mRECIST/iRECIST/RECIST1.1, with no cases of pseudoprogression. Median OS and median TTP were 717 days and 127 days for RECIST1.1/mRECIST/iRECIST-iUPD (unconfirmed PD). Older age, MELD/Child-Pugh scores, AFP, prior transarterial radioembolization (TARE), and larger TL size were predictive of PD and/or poor OS using mRECIST/iRECIST. The strongest predictor of PD (HR = 2.49, 95% CI 1.29-4.81, p = 0.007) was TARE. The strongest predictor of poor OS was PD by mRECIST/iRECIST at 3 months (HR = 2.26, 95% CI 1.00-5.10, p = 0.05) with borderline significance. CONCLUSION: Our results show ORR of 21%, equivalent for mRECIST, iRECIST, and RECIST1.1 in patients with advanced HCC clinically treated with nivolumab.

Precision of MRI radiomics features in the liver and hepatocellular carcinoma.

OBJECTIVES: To assess the precision of MRI radiomics features in hepatocellular carcinoma (HCC) tumors and liver parenchyma. METHODS: The study population consisted of 55 patients, including 16 with untreated HCCs, who underwent two repeat contrast-enhanced abdominal MRI exams within 1 month to evaluate: (1) test-retest repeatability using the same MRI system (n = 28, 10 HCCs); (2) inter-platform reproducibility between different MRI systems (n = 27, 6 HCCs); (3) inter-observer reproducibility (n = 16, 16 HCCs). Shape and 1st- and 2nd-order radiomics features were quantified on pre-contrast T1-weighted imaging (WI), T1WI portal venous phase (pvp), T2WI, and ADC (apparent diffusion coefficient), on liver regions of interest (ROIs) and HCC volumes of interest (VOIs). Precision was assessed by calculating intraclass correlation coefficient (ICC), concordance correlation coefficient (CCC), and coefficient of variation (CV). RESULTS: There was moderate to excellent test-retest repeatability of shape and 1st- and 2nd-order features for all sequences in HCCs (ICC: 0.53-0.99; CV: 3-29%), and moderate to good test-retest repeatability of 1st- and 2nd-order features for T1WI sequences, and 2nd-order features for T2WI in the liver (ICC: 0.53-0.73; CV: 12-19%). There was poor inter-platform reproducibility for all features and sequences, except for shape and 1st-order features on T1WI in HCCs (CCC: 0.58-0.99; CV: 3-15%). Good to excellent inter-observer reproducibility was found for all features and sequences in HCCs (CCC: 0.80-0.99; CV: 4-15%) and moderate to good for liver (CCC: 0.45-0.86; CV: 6-25%). CONCLUSIONS: MRI radiomics features have acceptable repeatability in the liver and HCC when using the same MRI system and across readers but have low reproducibility across MR systems, except for shape and 1st-order features on T1WI. Data must be interpreted with caution when performing multiplatform radiomics studies. KEY POINTS: • MRI radiomics features have acceptable repeatability when using the same MRI system but less reproducible when using different MRI platforms. • MRI radiomics features extracted from T1 weighted-imaging show greater stability across exams than T2 weighted-imaging and ADC. • Inter-observer reproducibility of MRI radiomics features was found to be good in HCC tumors and acceptable in liver parenchyma.

Constrictive and Hypertrophic Strictures in Ileal Crohn's Disease.

BACKGROUND & AIMS: Strictures in Crohn's disease (CD) are classically attributed to fibromuscular hypertrophy of the intestinal wall. We have identified and characterized CD-related ileal strictures that result instead from mural constriction (ie, reduced external circumference). METHODS: Twenty-four strictures and internal controls from 17 adults with obstructive CD were analyzed by cross-sectional morphometry. RESULTS: The stricture-to-control circumference ratios (CRs) ranged from 0.53 to 1.7. Six strictures with CR ≥1.0, designated hypertrophic, had concentrically thickened walls, mean 3-fold increases in cross-sectional area and stainable fibromucular tissue, and high transmural inflammation scores. In contrast, 18 strictures with CR <1.0, designated constrictive, had thin, pliant walls, cross-sectional areas and stainable fibromuscular tissue comparable with control values, and low transmural inflammation scores. Eight mildly constrictive strictures also showed mild fibromuscular mural expansion that fell short of statistical significance. Twelve of 18 constrictive strictures (67%) occurred multiply (2-4 strictures per specimen) in contrast with hypertrophic strictures, all of which occurred singly (P = .01). Constriction correlated quantitatively with circumferential serosal fat wrapping (P = .003) and was associated with myenteric lymphocytic plexitis (P = .02). Disease duration was shortest among subjects with constrictive strictures and correlated with increasing circumference (CR ≤0.8, 6.3 ± 6.2 years; CR >0.8, 8.7 ± 6.4 years; and CR ≥1.00, 13.7 ± 5.0 years, respectively; P = .03). CONCLUSIONS: Constrictive ileal strictures in CD differ pathologically and clinically from hypertrophic strictures, featuring little or no fibromuscular mural expansion, frequent multiplicity, and earlier onset. Mesenteric fat wrapping and myenteric plexitis may contribute to their pathogenesis. Pathologic manifestations of constriction and hypertrophy can coexist, suggesting that stricture heterogeneity may be shaped in part by the dynamics of constrictive and hypertrophic processes.

Quantitative chest CT combined with plasma cytokines predict outcomes in COVID-19 patients.

Despite extraordinary international efforts to dampen the spread and understand the mechanisms behind SARS-CoV-2 infections, accessible predictive biomarkers directly applicable in the clinic are yet to be discovered. Recent studies have revealed that diverse types of assays bear limited predictive power for COVID-19 outcomes. Here, we harness the predictive power of chest CT in combination with plasma cytokines using a machine learning approach for predicting death during hospitalization and maximum severity degree in COVID-19 patients. Patients (n=152) from the Mount Sinai Health System in New York with plasma cytokine assessment and a chest CT within 5 days from admission were included. Demographics, clinical, and laboratory variables, including plasma cytokines (IL-6, IL-8, and TNF-α) were collected from the electronic medical record. We found that chest CT combined with plasma cytokines were good predictors of death (AUC 0.78) and maximum severity (AUC 0.82), whereas CT quantitative was better at predicting severity (AUC 0.81 vs 0.70) while cytokine measurements better predicted death (AUC 0.70 vs 0.66). Finally, we provide a simple scoring system using plasma IL-6, IL-8, TNF-α, GGO to aerated lung ratio and age as novel metrics that may be used to monitor patients upon hospitalization and help physicians make critical decisions and considerations for patients at high risk of death for COVID-19.

Phase Ib dose-escalation study of the hypoxia-modifier Myo-inositol trispyrophosphate in patients with hepatopancreatobiliary tumors.

Hypoxia is prominent in solid tumors and a recognized driver of malignancy. Thus far, targeting tumor hypoxia has remained unsuccessful. Myo-inositol trispyrophosphate (ITPP) is a re-oxygenating compound without apparent toxicity. In preclinical models, ITPP potentiates the efficacy of subsequent chemotherapy through vascular normalization. Here, we report the results of an unrandomized, open-labeled, 3 + 3 dose-escalation phase Ib study (NCT02528526) including 28 patients with advanced primary hepatopancreatobiliary malignancies and liver metastases of colorectal cancer receiving nine 8h-infusions of ITPP over three weeks across eight dose levels (1'866-14'500 mg/m2/dose), followed by standard chemotherapy. Primary objectives are assessment of the safety and tolerability and establishment of the maximum tolerated dose, while secondary objectives include assessment of pharmacokinetics, antitumor activity via radiological evaluation and assessment of circulatory tumor-specific and angiogenic markers. The maximum tolerated dose is 12,390 mg/m2, and ITPP treatment results in 32 treatment-related toxicities (mostly hypercalcemia) that require little or no intervention. 52% of patients have morphological disease stabilization under ITPP monotherapy. Following subsequent chemotherapy, 10% show partial responses while 60% have stable disease. Decreases in angiogenic markers are noted in ∼60% of patients after ITPP and tend to correlate with responses and survival after chemotherapy.

Dynamic contrast-enhanced MRI perfusion quantification in hepatocellular carcinoma: comparison of gadoxetate disodium and gadobenate dimeglumine.

OBJECTIVES: (1) To assess the quality of the arterial input function (AIF) during dynamic contrast-enhanced (DCE) MRI of the liver and (2) to quantify perfusion parameters of hepatocellular carcinoma (HCC) and liver parenchyma during the first 3 min post-contrast injection with DCE-MRI using gadoxetate disodium compared to gadobenate dimeglumine (Gd-BOPTA) in different patient populations. METHODS: In this prospective study, we evaluated 66 patients with 83 HCCs who underwent DCE-MRI, using gadoxetate disodium (group 1, n = 28) or Gd-BOPTA (group 2, n = 38). AIF qualitative and quantitative features were assessed. Perfusion parameters (based on the initial 3 min post-contrast) were extracted in tumours and liver parenchyma, including model-free parameters (time-to-peak enhancement (TTP), time-to-washout) and modelled parameters (arterial flow (Fa), portal venous flow (Fp), total flow (Ft), arterial fraction, mean transit time (MTT), distribution volume (DV)). In addition, lesion-to-liver contrast ratios (LLCRs) were measured. Fisher's exact tests and Mann-Whitney U tests were used to compare the two groups. RESULTS: AIF quality, modelled and model-free perfusion parameters in HCC were similar between the 2 groups (p = 0.054-0.932). Liver parenchymal flow was lower and liver enhancement occurred later in group 1 vs group 2 (Fp, p = 0.002; Ft, p = 0.001; TTP, MTT, all p < 0.001), while there were no significant differences in tumour LLCR (max. positive LLCR, p = 0.230; max. negative LLCR, p = 0.317). CONCLUSION: Gadoxetate disodium provides comparable AIF quality and HCC perfusion parameters compared to Gd-BOPTA during dynamic phases. Despite delayed and decreased liver enhancement with gadoxetate disodium, LLCRs were equivalent between contrast agents, indicating similar tumour conspicuity. KEY POINTS: • Arterial input function quality, modelled, and model-free dynamic parameters measured in hepatocellular carcinoma are similar in patients receiving gadoxetate disodium or gadobenate dimeglumine during the first 3 min post injection. • Gadoxetate disodium and gadobenate dimeglumine show similar lesion-to-liver contrast ratios during dynamic phases in patients with HCC. • There is lower portal and lower total hepatic flow and longer hepatic mean transit time and time-to-peak with gadoxetate disodium compared to gadobenate dimeglumine.

Impact of different phased-array coils on the quality of prostate magnetic resonance 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 <0.004 for quantitative and p-values <0.017 for qualitative image analysis were considered statistically significant. RESULTS: Significantly higher SNR was found in T2W-TSE images in the TZ using 60CH BPA compared to 18CH BPA coil setups (15.20 ± 4.22 vs. 7.68 ± 2.37; p = 0.001). There were no significant differences between all other quantitative (T2W-TSE, p = 0.007-0.308; DWI, p = 0.024-0.574) and qualitative image features (T2W-TSE, p = 0.083-1.0; DWI, p = 0.046-1.0). CONCLUSION: 60CH BPA receive coil setup showed marginal SNR improvement in T2W-TSE images. Good IQ could be achieved with 18CH BPA coil setups.

4D flow MRI for the assessment of renal transplant dysfunction: initial results.

OBJECTIVES: (1) Determine inter-observer reproducibility and test-retest repeatability of 4D flow parameters in renal allograft vessels; (2) determine if 4D flow measurements in the renal artery (RA) and renal vein (RV) can distinguish between functional and dysfunctional allografts; (3) correlate haemodynamic parameters with estimated glomerular filtration rate (eGFR), perfusion measured with dynamic contrast-enhanced MRI (DCE-MRI) and histopathology. METHODS: Twenty-five prospectively recruited renal transplant patients (stable function/chronic renal allograft dysfunction, 12/13) underwent 4D flow MRI at 1.5 T. 4D flow coronal oblique acquisitions were performed in the transplant renal artery (RA) (velocity encoding parameter, VENC = 120 cm/s) and renal vein (RV) (VENC = 45 cm/s). Test-retest repeatability (n = 3) and inter-observer reproducibility (n = 10) were assessed by Cohen's kappa, coefficient of variation (CoV) and Bland-Altman statistics. Haemodynamic parameters were compared between patients and correlated to the estimated glomerular filtration rate, DCE-MRI parameters (n = 10) and histopathology from allograft biopsies (n = 15). RESULTS: For inter-observer reproducibility, kappa was > 0.99 and 0.62 and CoV of flow was 12.6% and 7.8% for RA and RV, respectively. For test-retest repeatability, kappa was > 0.99 and 0.5 and CoV of flow was 27.3% and 59.4%, for RA and RV, respectively. RA (p = 0.039) and RV (p = 0.019) flow were both significantly reduced in dysfunctional allografts. Both identified chronic allograft dysfunction with good diagnostic performance (RA: AUC = 0.76, p = 0.036; RV: AUC = 0.8, p = 0.018). RA flow correlated negatively with histopathologic interstitial fibrosis score ci (ρ = - 0.6, p = 0.03). CONCLUSIONS: 4D flow parameters had better repeatability in the RA than in the RV. RA and RV flow can identify chronic renal allograft dysfunction, with RA flow correlating with histopathologic interstitial fibrosis score. KEY POINTS: • Inter-observer reproducibility of 4D flow measurements was acceptable in both the transplant renal artery and vein, but test-retest repeatability was better in the renal artery than in the renal vein. • Blood flow measurements obtained with 4D flow MRI in the renal artery and renal vein are significantly reduced in dysfunctional renal transplants. • Renal transplant artery flow correlated negatively with histopathologic interstitial fibrosis score.