A data management infrastructure for the integration of imaging and omics data in life sciences.

BACKGROUND: As technical developments in omics and biomedical imaging increase the throughput of data generation in life sciences, the need for information systems capable of managing heterogeneous digital assets is increasing. In particular, systems supporting the findability, accessibility, interoperability, and reusability (FAIR) principles of scientific data management. RESULTS: We propose a Service Oriented Architecture approach for integrated management and analysis of multi-omics and biomedical imaging data. Our architecture introduces an image management system into a FAIR-supporting, web-based platform for omics data management. Interoperable metadata models and middleware components implement the required data management operations. The resulting architecture allows for FAIR management of omics and imaging data, facilitating metadata queries from software applications. The applicability of the proposed architecture is demonstrated using two technical proofs of concept and a use case, aimed at molecular plant biology and clinical liver cancer research, which integrate various imaging and omics modalities. CONCLUSIONS: We describe a data management architecture for integrated, FAIR-supporting management of omics and biomedical imaging data, and exemplify its applicability for basic biology research and clinical studies. We anticipate that FAIR data management systems for multi-modal data repositories will play a pivotal role in data-driven research, including studies which leverage advanced machine learning methods, as the joint analysis of omics and imaging data, in conjunction with phenotypic metadata, becomes not only desirable but necessary to derive novel insights into biological processes.

Head-to-head comparison of biparametric versus multiparametric MRI of the prostate before robot-assisted transperineal fusion prostate biopsy.

PURPOSE: Prostate biparametric magnetic resonance imaging (bpMRI) including T2-weighted imaging (T2WI) and diffusion-weighted imaging (DWI) might be an alternative to multiparametric MRI (mpMRI, including dynamic contrast imaging, DCE) to detect and guide targeted biopsy in patients with suspected prostate cancer (PCa). However, there is no upgrading peripheral zone PI-RADS 3 to PI-RADS 4 without DCE in bpMRI. The aim of this study was to evaluate bpMRI against mpMRI in biopsy-naïve men with elevated prostate-specific antigen (PSA) scheduled for robot-assisted-transperineal fusion-prostate biopsy (RA-TB). METHODS: Retrospective single-center-study of 563 biopsy-naïve men (from 01/2015 to 09/2018, mean PSA 9.7 ± 6.5 ng/mL) with PI-RADSv2.1 conform mpMRI at 3 T before RA-TB. Clinically significant prostate cancer (csPCa) was defined as ISUP grade ≥ 2 in any core. Two experienced readers independently evaluated images according to PI-RADSv2.1 criteria (separate readings for bpMRI and mpMRI sequences, 6-month interval). Reference standard was histology from RA-TB. RESULTS: PI-RADS 2 was scored in 5.1% of cases (3.4% cancer/3.4% csPCa), PI-RADS 3 in 16.9% (32.6%/3.2%), PI-RADS 4 in 57.6% (66.1%/58.3%) and PI-RADS 5 in 20.4% of cases (79.1%/74.8%). For mpMRI/bpMRI test comparison, sensitivity was 99.0%/97.1% (p < 0.001), specificity 47.5%/61.2% (p < 0.001), PPV 69.5%/75.1% (p < 0.001) and NPV 97.6%/94.6% (n.s.). csPCa was considered gold standard. 35 cases without cancer were upgraded to PI-RADS 4 (mpMRI) and six PI-RADS 3 cases with csPCa were not upgraded (bpMRI). CONCLUSION: In patients planned for RA-TB with elevated PSA and clinical suspicion for PCa, specificity was higher in bpMRI vs. mpMRI, which could solve constrains regarding time and contrast agent.

T2 mapping for the characterization of prostate lesions.

PURPOSE: Purpose of this study is to evaluate the diagnostic accuracy of quantitative T2/ADC values in differentiating between PCa and lesions showing non-specific inflammatory infiltrates and atrophy, features of chronic prostatitis, as the most common histologically proven differential diagnosis. METHODS: In this retrospective, single-center cohort study, we analyzed 55 patients suspected of PCa, who underwent mpMRI (3T) including quantitative T2 maps before robot-assisted mpMRI-TRUS fusion prostate biopsy. All prostate lesions were scored according to PI-RADS v2.1. Regions of interest (ROIs) were annotated in focal lesions and normal prostate tissue. Quantitative mpMRI values from T2 mapping and ADC were compared using two-tailed t tests. Receiver operating characteristic curves (ROCs) and cutoff were calculated to differentiate between PCa and chronic prostatitis. RESULTS: Focal lesions showed significantly lower ADC and T2 mapping values than normal prostate tissue (p < 0.001). PCa showed significantly lower ADC and T2 values than chronic prostatitis (p < 0.001). ROC analysis revealed areas under the receiver operating characteristic curves (AUCs) of 0.85 (95% CI 0.74-0.97) for quantitative ADC values and 0.84 (95% CI 0.73-0.96) for T2 mapping. A significant correlation between ADC and T2 values was observed (r = 0.70; p < 0.001). CONCLUSION: T2 mapping showed high diagnostic accuracy for differentiating between PCa and chronic prostatitis, comparable to the performance of ADC values.

Noninvasive, longitudinal imaging-based analysis of body adipose tissue and water composition in a melanoma mouse model and in immune checkpoint inhibitor-treated metastatic melanoma patients.

BACKGROUND: As cancer cachexia (CC) is associated with cancer progression, early identification would be beneficial. The aim of this study was to establish a workflow for automated MRI-based segmentation of visceral (VAT) and subcutaneous adipose tissue (SCAT) and lean tissue water (LTW) in a B16 melanoma animal model, monitor diseases progression and transfer the protocol to human melanoma patients for therapy assessment. METHODS: For in vivo monitoring of CC B16 melanoma-bearing and healthy mice underwent longitudinal three-point DIXON MRI (days 3, 12, 17 after subcutaneous tumor inoculation). In a prospective clinical study, 18 metastatic melanoma patients underwent MRI before, 2 and 12 weeks after onset of checkpoint inhibitor therapy (CIT; n = 16). We employed an in-house MATLAB script for automated whole-body segmentation for detection of VAT, SCAT and LTW. RESULTS: B16 mice exhibited a CC phenotype and developed a reduced VAT volume compared to baseline (B16 - 249.8 µl, - 25%; controls + 85.3 µl, + 10%, p = 0.003) and to healthy controls. LTW was increased in controls compared to melanoma mice. Five melanoma patients responded to CIT, 7 progressed, and 6 displayed a mixed response. Responding patients exhibited a very limited variability in VAT and SCAT in contrast to others. Interestingly, the LTW was decreased in CIT responding patients (- 3.02% ± 2.67%; p = 0.0034) but increased in patients with progressive disease (+ 1.97% ± 2.19%) and mixed response (+ 4.59% ± 3.71%). CONCLUSION: MRI-based segmentation of fat and water contents adds essential additional information for monitoring the development of CC in mice and metastatic melanoma patients during CIT or other treatment approaches.

Simultaneous whole-body PET/MRI with integrated multiparametric MRI for primary staging of high-risk prostate cancer.

PURPOSE: Whole-body positron emission tomography/magnetic resonance imaging (wbPET/MRI) is a promising diagnostic tool of recurrent prostate cancer (PC), but its role in primary staging of high-risk PC (hrPC) is not well defined. Thus, the aim was to compare the diagnostic accuracy for T-staging of PET-blinded reading (PBR) and PET/MRI. METHODS: In this prospective study, hrPC patients scheduled to radical prostatectomy (RPx) with extended lymphadenectomy (eLND) were staged with wbPET/MRI and either 68Ga-PSMA-11 or 11C-choline including simultaneous multiparametric MRI (mpMRI). Images were assessed in two sessions, first as PBR (mpMRI and wbMRI) and second as wbPET/MRI. Prostate Imaging Reporting and Data System criteria (PIRADS v2) were used for T-staging. Results were correlated with the exact anatomical localization and extension as defined by histopathology. Diagnostic accuracy of cTNM stage according to PBR was compared to pathological pTNM stage as reference standard. RESULTS: Thirty-four patients underwent wbPET/MRI of 68Ga-PSMA-11 (n = 17) or 11C-choline (n = 17). Twenty-four patients meeting the inclusion criteria of localized disease ± nodal disease based on imaging results underwent RPx and eLND, whereas ten patients were excluded from analysis due to metastatic disease. T-stage was best defined by mpMRI with underestimation of tumor lesion size by PET for both tracers. N-stage yielded a per patient sensitivity/specificity comparable to PBR. CONCLUSION: MpMRI is the primary modality for T-staging in hrPC as PET underestimated T-stage in direct comparison to final pathology. In this selected study, cohort MRI shows no inferiority compared to wbPET/MRI considering N-staging.

Can contrast-enhanced ultrasound and acoustic radiation force impulse imaging characterize CT-indeterminate renal masses? A prospective evaluation with histological confirmation.

PURPOSE: To prospectively characterize computed tomography (CT)-indeterminate renal masses (CTIRM) using acoustic radiation force impulse (ARFI) elastography and contrast-enhanced ultrasound (CEUS) and to correlate quantitative imaging findings with histopathology or interim follow-up (FU). METHODS: 123 patients with CTIRM (longest diameter < 4 cm) underwent ARFI and CEUS with CT image fusion (IF). Exclusion criteria included all contraindications for CEUS and IF. Shear wave velocity (SWV), shear wave ratio (SWR), peak intensity (PE), time to peak (TTP) and wash-in rate (Wi) were quantified. In case of a cystic lesion classified as ≤ Bosniak 2F, follow-up imaging was performed. RESULTS: 77 out of 123 patients underwent surgical resection of a lesion due to suspect imaging findings, whereas 46 patients underwent FU, which did not show upgrading in Bosniak category. Histopathology revealed 58 renal cell carcinomas [five chromophobe (chRCC), 18 papillary (pRCC) and 35 clear cell (ccRCC)], ten oncocytomas and nine non-malignant renal lesions (one minimal fat AML, three focal nephritis and five infected cysts). SWV and SWR differed significantly between ccRCC, pRCC, chRCC (p = 0.0024, F = 13.94) and in SWR also for oncocytoma (p < 0.0001, F = 14.35). In CEUS, oncocytoma and ccRCC showed significant higher PE values (p < 0.0001, F = 77.31) as well as higher Wi and lower TTP compared to all other solid lesions. CONCLUSIONS: Quantitative CEUS and ARFI imaging can provide relevant information to further characterize CT-indeterminate renal masses to guide urological decision making and offer the possibility of differentiation between ccRCC from less malignant RCC subtypes and from oncocytoma.

Prognostic value of perfusion CT in hepatocellular carcinoma treatment with sorafenib: comparison with mRECIST in longitudinal follow-up.

Background Targeted therapies are of increasing clinical importance and classic radiologic therapy response-criteria often fail to detect early therapeutic response or failure. For hepatocellular carcinoma (HCC), this is of major importance as therapeutic options are limited. Purpose To investigate the impact of sorafenib-treatment on intralesional perfusion using perfusion computed tomography (PCT) in HCC and to correlate the observed changes with mRECIST and the course of serum alpha-fetoprotein (AFP) for identification of their prognostic value. Material and Methods PCT was performed before and after two months of sorafenib treatment in 28 consecutive HCC patients and AFP levels were registered. Changes in tumor perfusion parameters blood flow (BF), blood volume (BV), mean transit time (MTT), volume transfer constant (Ktrans), arterial liver perfusion (ALP), and hepatic perfusion index (HPI) were registered in one target lesion. mRECIST measurements were performed at baseline and after two and four months during sorafenib treatment. Results According to mRECIST, after two months of treatment, all patients showed stable disease (SD), whereas after four months, 13 patients (46%) showed SD and 15 patients (54%) showed progressive disease (PD). A significant decrease was found in perfusion parameters BF, BV, Ktrans, ALP, and HPI in patients with SD as well as a significant increase in MTT ( P < 0.05) after two months compared to baseline, while patients with PD showed a significant increase in HPI, BF, and BV. There were no correlations between AFP and mRECIST or perfusion parameters. Conclusion Decreased intralesional BF and HPI after two months of sorafenib treatment predicts disease stabilization after four months, whereas AFP dynamics were of limited value.

Improved MDCT monitoring of pelvic myeloma bone disease through the use of a novel longitudinal bone subtraction post-processing algorithm.

PURPOSE: To evaluate the diagnostic performance of a novel CT post-processing software that generates subtraction maps of baseline and follow-up CT examinations in the course of myeloma bone lesions. MATERIALS AND METHODS: This study included 61 consecutive myeloma patients who underwent repeated whole-body reduced-dose MDCT at our institution between November 2013 and June 2015. CT subtraction maps classified a progressive disease (PD) vs. stable disease (SD)/remission. Bone subtraction maps (BSMs) only and in combination with 1-mm (BSM+) source images were compared with 5-mm axial/MPR scans. RESULTS: Haematological response categories at follow-up were: complete remission (n = 9), very good partial remission (n = 2), partial remission (n = 17) and SDh (n = 19) vs. PDh (n = 14). Five-millimetre CT scan yielded PD (n = 14) and SD/remission (n = 47) whereas bone subtraction + 1-mm axial scans (BSM+) reading resulted in PD (n = 18) and SD/remission (n = 43). Sensitivity/ specificity/accuracy for 5-mm/1-mm/BSM(alone)/BSM + in "lesion-by-lesion" reading was 89.4 %/98.9 %/98.3 %/ 99.5 %; 69.1 %/96.9 %/72 %/92.1 % and 83.8 %/98.4 %/92.1 %/98.3 %, respectively. The use of BSM+ resulted in a change of response classification in 9.8 % patients (n = 6) from SD to PD. CONCLUSION: BSM reading is more accurate for monitoring myeloma compared to axial scans whereas BSM+ yields similar results with 1-mm reading (gold standard) but by significantly reduced reading time. KEY POINTS: • CT evaluation of myeloma bone disease using a longitudinal bone subtraction post-processing algorithm. • Bone subtraction post-processing algorithm is more accurate for assessment of therapy. • Bone subtraction allowed improved and more efficient detection of myeloma bone lesions. • Post-processing tool demonstrating a change in response classification in 9.8 % patients (all showing PD). • Reading time could be substantially shortened as compared to regular CT assessment.

Impact of transjugular intrahepatic portosystemic shunt implantation on liver perfusion measured by volume perfusion CT.

Background Implantation of a transjugular intrahepatic portosystemic shunt (TIPS) induces changes of liver perfusion. Purpose To determine the changes in arterial, portal venous, and total perfusion of the liver parenchyma induced by TIPS using the technique of volume perfusion computed tomography (VPCT) and compare results with invasively measured hepatic intravascular pressure values. Material and Methods VPCT quantification of liver perfusion was performed in 23 patients (mean age, 62.5 ± 8.8 years) with portal hypertension in the pre-TIPS and post-TIPS setting, respectively. A commercially available software package was used for post-processing, enabling separate calculation of the dual (arterial [ALP] and portal venous [PVP]) blood supply and additionally of the hepatic perfusion index (HPI) (HPI = ALP/(ALP + PVP)*100%). Invasive pressure measurements were performed during the intervention, before and after TIPS placement. Liver function tests performed before and after the procedure were compared. Results Mean decrease of pressure gradient through TIPS was 13.3 mmHg. Mean normal values for ALP, PVP, and total perfusion (ALP + PVP) before TIPS were 15.9, 37.7, and 53.5 mL/100 mL/min, respectively, mean HPI was 35.4%. After TIPS, ALP increased to a mean value of 37.7 mL/100 mL/min, PVP decreased (15.7 mL/100 mL/min, P < 0.05), whereas total perfusion remained unchanged (53.4 mL/100 mL/min, P = 0.97). HPI increased (71.9%; P < 0.05). No correlation between invasive pressure measurement and VPCT parameters was observed. After TIPS, liver function tests were found to worsen with a significant increase of bilirubin ( P < 0.05). Conclusion Following TIPS placement, ALP and HPI increased in all patients, whereas PVP markedly decreased. Interestingly, the magnitude of decrease in portosystemic pressure gradients was not found to correlate with VPCT parameters.

Iodine concentration as a perfusion surrogate marker in oncology: Further elucidation of the underlying mechanisms using Volume Perfusion CT with 80 kVp.

OBJECTIVES: To assess the value of iodine concentration (IC) in computed tomography data acquired with 80 kVp, as a surrogate for perfusion imaging in hepatocellular carcinoma (HCC) and lymphoma by comparing iodine related attenuation (IRA) with quantitative Volume Perfusion CT (VPCT)-parameters. METHODS: VPCT-parameters were compared with intra-tumoral IC at 5 time points after the aortic peak enhancement (APE) with a temporal resolution of 3.5 sec in untreated 30 HCC and 30 lymphoma patients. RESULTS: Intra-tumoral perfusion parameters for HCC showed a blood flow (BF) of 52.7 ± 17.0 mL/100 mL/min, blood volume (BV) 12.6 ± 4.3 mL/100 mL, arterial liver perfusion (ALP) 44.4 ± 12.8 mL/100 mL/min. Lesion IC 7 sec after APE was 133.4 ± 57.3 mg/100 mL. Lymphoma showed a BF of 36.8 ± 13.4 mL/100 mL/min, BV of 8.8 ± 2.8 mL/100 mL and IC of 118.2 ± 64.5 mg/100 mL 3.5 sec after APE. Strongest correlations exist for VPCT-derived BF and ALP with IC in HCC 7 sec after APE (r = 0.71 and r = 0.84) and 3.5 sec after APE in lymphoma lesions (r = 0.77). Significant correlations are also present for BV (r = 0.60 and r = 0.65 for HCC and lymphoma, respectively). CONCLUSIONS: We identified a good, time-dependent agreement between VPCT-derived flow values and IC in HCC and lymphoma. Thus, CT-derived ICs 7 sec after APE in HCC and 3.5 sec in lymphoma may be used as surrogate imaging biomarkers for tumor perfusion with 80 kVp. KEY POINTS: • Iodine concentration derived from low kVp CT is regarded as perfusion surrogate • Correlation with Perfusion CT was performed to elucidate timing and histology dependencies • Highest correlation was present 7 sec after aortic peak enhancement in hepatocellular carcinoma • In lymphoma, highest correlation was calculated 3.5 sec after aortic peak enhancement • With these results, further optimization of Dual energy CT protocols is possible.

Gastroenteropancreatic Neuroendocrine Tumors-Current Status and Advances in Diagnostic Imaging.

Gastroenteropancreatic neuroendocrine neoplasia (GEP-NEN) is a heterogeneous and complex group of tumors that are often difficult to classify due to their heterogeneity and varying locations. As standard radiological methods, ultrasound, computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography-computed tomography (PET/CT) are available for both localization and staging of NEN. Nuclear medical imaging methods with somatostatin analogs are of great importance since radioactively labeled receptor ligands make tumors visible with high sensitivity. CT and MRI have high detection rates for GEP-NEN and have been further improved by developments such as diffusion-weighted imaging. However, nuclear medical imaging methods are superior in detection, especially in gastrointestinal NEN. It is important for radiologists to be familiar with NEN, as it can occur ubiquitously in the abdomen and should be identified as such. Since GEP-NEN is predominantly hypervascularized, a biphasic examination technique is mandatory for contrast-enhanced cross-sectional imaging. PET/CT with somatostatin analogs should be used as the subsequent method.

18F-FDG-PET/MR in Alveolar Echinococcosis: Multiparametric Imaging in a Real-World Setting.

Recent improvements in alveolar echinococcosis (AE) therapy can provide long-term disease control, and even allow structured treatment interruption in selected cases. Imaging has a pivotal role in monitoring disease activity, with 18-fluoro-deoxyglucose positron emission and computed tomography (18F-FDG-PET/CT) in particular having proven beneficial for assessing disease activity. Repetitive regular examinations to monitor therapy response, however, can lead to substantial radiation burden. Therefore, by combining metabolic information and excellent tissue contrast in magnetic resonance imaging (MRI), PET/MR appears ideally suited for this task. Here, we retrospectively analyzed 51 AE patients that underwent 18F-FDG-PET/MR. Patients had a 'confirmed/probable' diagnosis in 22/29 cases according to the WHO classification. FDG uptake, diffusion restriction, and MRI morphology were evaluated. We found significant differences in FDG uptake between responders to benzimidazole therapy and progressive manifestations (SUVavg 2.7 ± 1.3 vs. 5.4 ± 2.2, p < 0.001) as well as between Kodama Types 1 and 3 (F = 9.9, p < 0.003). No significant differences were detected for ADC values or MRI morphology concerning response and no correlations were present between FDG uptake and ADC values. The mean radiation dose was 5.9−6.5 mSv. We conclude that the combination of metabolic information and MRI morphology at a low radiation dose proposes PET/MR as a suitable imaging modality for AE assessment. Longitudinal studies are needed to define the role of this imaging modality.

Is a single portal venous phase in contrast-enhanced CT sufficient to detect metastases or recurrence in clear cell renal cell carcinoma? - a single-center retrospective study.

BACKGROUND: This study aims at describing the imaging features of the metastatic presentation of clear cell renal cell carcinoma (ccRCC) in arterial (AP) and portal venous phase (PVP) of contrast-enhanced-computed-tomography (CECT) during clinical follow-up (FU) and to evaluate the necessity of a dual phase approach for metastasis detection. METHODS: We identified a total of 584 patients that were diagnosed with ccRCC between January 2016 and April 2020. Inclusion criteria were histologically proven ccRCC with metastatic spread, proven by histology or interim follow-up of at least 2 years and follow-up CT examination with AP and PVP CECT including thorax/abdomen and pelvis. Exclusion criteria were defined by missing or incomplete CT-scans or lack of sufficient follow-up. CT studies of 43 patients with histologically proven ccRCCs were analyzed in retrospect. AP and PVP images were analyzed by two radiologists for metastases, two additional independent radiologists analyzed PVP images only. A 5-point Likert scale was used to evaluate the likelihood off the presence of metastasis. Imaging patterns of the metastases were analyzed visually. RESULTS: 43 patients (16 female; mean age: 67±10 years) with recurrent ccRCC and metastatic disease were included. Three imaging patterns were observed (solid, heterogeneous or cystic metastases), which rarely exhibited calcifications (2%). All metastases showed hyperenhancement in AP and PVP. Inter-reader agreement was substantial (Fleiss' κ 0.6-0.8, p<0.001). No significant differences in sensitivity or specificity between readers (AP and PVP images vs. PVP images only) were present (79.4-85.2%, 97.1-99.6%, p ≥ 0.05). The area under the receiver-operating-characteristic (ROC) curve was between 0.901and 0.922 for all four radiologists. CONCLUSIONS: Similar rates for detection, sensitivity and specificity of metastasis and local recurrence in ccRCC were observed irrespective of using a dual-phase protocol with AP and PVP or a single PVP protocol only. Thus, a single-phase examination of PVP can be sufficient for experienced radiologists to detect metastatic disease in the follow-up of ccRCC patients.

Deep Neural Networks and Machine Learning Radiomics Modelling for Prediction of Relapse in Mantle Cell Lymphoma.

Mantle cell lymphoma (MCL) is a rare lymphoid malignancy with a poor prognosis characterised by frequent relapse and short durations of treatment response. Most patients present with aggressive disease, but there exist indolent subtypes without the need for immediate intervention. The very heterogeneous behaviour of MCL is genetically characterised by the translocation t(11;14)(q13;q32), leading to Cyclin D1 overexpression with distinct clinical and biological characteristics and outcomes. There is still an unfulfilled need for precise MCL prognostication in real-time. Machine learning and deep learning neural networks are rapidly advancing technologies with promising results in numerous fields of application. This study develops and compares the performance of deep learning (DL) algorithms and radiomics-based machine learning (ML) models to predict MCL relapse on baseline CT scans. Five classification algorithms were used, including three deep learning models (3D SEResNet50, 3D DenseNet, and an optimised 3D CNN) and two machine learning models based on K-nearest Neighbor (KNN) and Random Forest (RF). The best performing method, our optimised 3D CNN, predicted MCL relapse with a 70% accuracy, better than the 3D SEResNet50 (62%) and the 3D DenseNet (59%). The second-best performing method was the KNN-based machine learning model (64%) after principal component analysis for improved accuracy. Our optimised CNN developed by ourselves correctly predicted MCL relapse in 70% of the patients on baseline CT imaging. Once prospectively tested in clinical trials with a larger sample size, our proposed 3D deep learning model could facilitate clinical management by precision imaging in MCL.

Longitudinal CT Imaging to Explore the Predictive Power of 3D Radiomic Tumour Heterogeneity in Precise Imaging of Mantle Cell Lymphoma (MCL).

The study's primary aim is to evaluate the predictive performance of CT-derived 3D radiomics for MCL risk stratification. The secondary objective is to search for radiomic features associated with sustained remission. Included were 70 patients: 31 MCL patients and 39 control subjects with normal axillary lymph nodes followed over five years. Radiomic analysis of all targets (n = 745) was performed and features selected using the Mann Whitney U test; the discriminative power of identifying "high-risk MCL" was evaluated by receiver operating characteristics (ROC). The four radiomic features, "Uniformity", "Entropy", "Skewness" and "Difference Entropy" showed predictive significance for relapse (p < 0.05)-in contrast to the routine size measurements, which showed no relevant difference. The best prognostication for relapse achieved the feature "Uniformity" (AUC-ROC-curve 0.87; optimal cut-off ≤0.0159 to predict relapse with 87% sensitivity, 65% specificity, 69% accuracy). Several radiomic features, including the parameter "Short Axis," were associated with sustained remission. CT-derived 3D radiomics improves the predictive estimation of MCL patients; in combination with the ability to identify potential radiomic features that are characteristic for sustained remission, it may assist physicians in the clinical management of MCL.

Diagnostic benefit of multiparametric MRI over contrast-enhanced CT in patients with bladder cancer: A single-center 1-year experience.

PURPOSE: To assess the clinical applicability of local tumor staging in urinary bladder cancer (BC) with preoperative multiparametric MRI (mpMRI) using the five-point Vesical Imaging-Reporting and Data System (VI-RADS) scoring system and to compare it to dual-phase contrast-enhanced computed tomography (CECT). METHODS: 33 patients with primary untreated bladder cancer underwent CECT followed by preoperative multiparametric 3.0 T MRI between July 2019 and August 2020 and were enrolled in this retrospective study. Two radiologists initially performed staging on the CECT image data sets and - blinded to CT results - on subsequent mpMRI. BCs were staged according to the VI-RADS scoring system. Postoperative pathology was correlated to the VI-RADS score and the CECT results. The performance of VI-RADS in determining detrusor muscle invasion was analyzed using a receiver operating characteristic curve. Based on the histopathology, sensitivity, specificity and accuracy for muscle invasiveness between both image modalities were compared using the Chi square test. RESULTS: A total of 33 patients (29 male, median age 70 years, IQR: 59-81 years) were included. 10 tumors were categorized as non-muscle invasive (30%) and 23 as muscle invasive BC (70%) in final histology. Tumor stages were correctly assigned as being either muscle invasive or non-muscle invasive on both CECT and mpMRI with regard to both early and late stages of BC (Ta-Tis and T3a-T4b). T-stages bordering the histopathologic limits of muscle invasiveness (T1-T2a-b) resulted in overestimation of muscle invasion in 43% of cases (VI-RADS 3-4) for the mpMRI image data sets and in an underestimation of muscle invasion in up to 55.5% of cases analysing the CECT data. Sensitivity and specificity for the determination of muscle invasion in CECT and mpMRI were 80%/80% and 74%/61% for Radiologist#1 and 70%/90% and 83%/70% for Radiologist#2, respectively. CONCLUSIONS: There are advantages and disadvantages of both CECT and mpMRI when used in the clinical assessment of BC muscular tumor invasion. In borderline cases, only the combination of cross-sectional imaging and histopathological staging may help in making the optimal treatment decisions.

Sonographic findings in coronavirus disease-19 associated liver damage.

PURPOSE: This study was conducted to evaluate the role of liver sonography in patients with coronavirus disease 2019 (COVID-19) and elevated liver enzymes. MATERIALS AND METHODS: In this retrospective study, patients tested positive for SARS-CoV-2 in our emergency ward between January 01 and April 24, 2020 and elevated liver enzymes were included (Cohort 1). Additionally, the local radiology information system was screened for sonographies in COVID-19 patients at the intensive care unit in the same period (Cohort 2). Liver sonographies and histologic specimen were reviewed and suspicious findings recorded. Medical records were reviewed for clinical data. Ultrasound findings and clinical data were correlated with severity of liver enzyme elevation. RESULTS: Cohort 1: 126 patients were evaluated, of which 47 (37.3%) had elevated liver enzymes. Severity of liver enzyme elevation was associated with death (p<0.001). 8 patients (6.3%) had suspicious ultrasound findings, including signs of acute hepatitis (n = 5, e.g. thickening of gall bladder wall, hepatomegaly, decreased echogenicity of liver parenchyma) and vascular complications (n = 4). Cohort 2: 39 patients were evaluated, of which 14 are also included in Cohort 1. 19 patients (48.7%) had suspicious ultrasound findings, of which 13 patients had signs of acute hepatitis and 6 had vascular complications. Pathology was performed in 6 patients. Predominant findings were severe cholestasis and macrophage activation. CONCLUSION: For most hospitalized COVID-19 patients, elevated liver enzymes cause little concern as they are only mild to moderate. However, in severely ill patients bedside sonography is a powerful tool to reveal different patterns of vascular, cholestatic or inflammatory complications in the liver, which are associated with high mortality. In addition, macrophage activation as histopathologic correlate for a hyperinflammatory syndrome seems to be a frequent complication in COVID-19.

Temporal Dynamics of Reactive Oxygen and Nitrogen Species and NF-κB Activation During Acute and Chronic T Cell-Driven Inflammation.

PURPOSE: Reactive oxygen and nitrogen species (ROS/RNS) production and the NF-κB activation are critically involved in inflammatory responses, but knowledge about the temporal dynamics during acute and chronic inflammation is limited. Here, we present a comparative longitudinal in vivo study of both parameters in an experimental model of acute and chronic T cell-driven delayed-type hypersensitivity reaction (DTHR) using noninvasive optical imaging. PROCEDURES: Trinitrochlorobenzene (TNCB)-sensitized NF-κB-luciferase-reporter and wild-type mice were TNCB challenged on the right ear to elicit acute DTHR and then repetitively challenged (up to five times) to induce chronic DTHR. Mice were treated with the ROS-scavenging and NF-κB inhibiting molecule N-acetylcysteine (NAC) or underwent sham treatment. ROS/RNS production was noninvasively analyzed in vivo using the ROS-/RNS-sensitive chemiluminescent probe L-012, and NF-κB activation was measured using NF-κB-luciferase-reporter mice. H&E staining, CD3 and myeloperoxidase (MPO) immunohistochemistry (IHC), and quantitative PCR (qPCR) analyses were employed to investigate immune cell infiltration and expression of NF-κB- and ROS-/RNS-driven genes. RESULTS: In acute DTHR, we found strongly elevated ROS/RNS production and NF-κB activation 12 h after the 1st TNCB ear challenge, peaking at 24 h after the challenge. In chronic DTHR, ROS production peaked as early as 4 h after the 5th TNCB challenge, whereas NF-κB activity peaked after 12 h. The increase in ROS/RNS production in acute DTHR was higher than the increase in NF-κB activity but the relationship was inverse in chronic DTHR. Treatment with the ROS scavenger NAC had differential effects on ROS/RNS production and NF-κB activation during acute and chronic DTHR. Ex vivo cross-validation by histopathology and qPCR analysis correlated closely with the in vivo imaging results. CONCLUSIONS: Noninvasive in vivo imaging is capable of assessing the temporal dynamics of ROS/RNS production and NF-κB activation during progression from acute to chronic DTHR and enables monitoring of anti-inflammatory treatment responses.

The scaffold protein p62 regulates adaptive thermogenesis through ATF2 nuclear target activation.

During ß-adrenergic stimulation of brown adipose tissue (BAT), p38 phosphorylates the activating transcription factor 2 (ATF2) which then translocates to the nucleus to activate the expression of Ucp1 and Pgc-1α. The mechanisms underlying ATF2 target activation are unknown. Here we demonstrate that p62 (Sqstm1) binds to ATF2 to orchestrate activation of the Ucp1 enhancer and Pgc-1α promoter. P62Δ69-251 mice show reduced expression of Ucp1 and Pgc-1α with impaired ATF2 genomic binding. Modulation of Ucp1 and Pgc-1α expression through p62 regulation of ATF2 signaling is demonstrated in vitro and in vivo in p62Δ69-251 mice, global p62-/- and Ucp1-Cre p62flx/flx mice. BAT dysfunction resulting from p62 deficiency is manifest after birth and obesity subsequently develops despite normal food intake, intestinal nutrient absorption and locomotor activity. In summary, our data identify p62 as a master regulator of BAT function in that it controls the Ucp1 pathway through regulation of ATF2 genomic binding.

CT-morphologic and CT-textural patterns of response in inoperable soft tissue sarcomas treated with pazopanib-a preliminary retrospective cohort study.

OBJECTIVE: To analyze patterns of response in soft tissue sarcomas exposed to pazopanib using CT-morphologic and textural features and their suitability for evaluating therapeutic response. METHODS: Retrospective evaluation of CT response and texture patterns in 33 patients (23 female; mean age: 61.2 years, range, 30-85 years) with soft tissue sarcomas treated with pazopanib from October 2008 to July 2017. Response evaluation was based on modified (m)CHOI-criteria and RECISTv.1.1 and classified as partial response (PR), stable disease (SD), progressive disease (PD). The following CT-texture (CTTA)-parameters were calculated: mean, entropy and uniformity of intensity/average/skewness/entropy of co-occurrence matrix and contrast of neighboring-gray-level-dependence-matrix. RESULTS: Following mCHOI-criteria, 12 patients achieved PR, 7 SD and 14 PD. As per RECISTv.1.1 9 patients obtained PR, 9 SD and 15 PD. Frequent patterns of response were tumor liquefaction and necrosis (n=4/33, 12.1% each). Further patterns included shrinkage and cavitation (n=2/33, 6.1% each). In responders, differences in mean heterogeneity (p=0.01), intensity (p=0.03), average (p=0.03) and entropy of skewness (p=0.01) were found at follow-up whereas in non-responders, CTTA-parameters did not change significantly. Baseline-CTTA-features differed between responders and non-responders in terms of uniformity of skewness (p=0.045). Baseline-CTTA-parameters did not correlate with any morphologic response pattern. CONCLUSION: Most frequent patterns of response to pazopanib were tumor liquefaction and necrosis. Single CT-textural features show strong association with the response to pazopanib-although limited in relation to specific response patterns. ADVANCES IN KNOWLEDGE: Tumor liquefication and necrosis are important patterns of response to pazopanib. CT-texture analysis has limited associations with specific response patterns.