Liver Investigation: Testing Marker Utility in Steatohepatitis (LITMUS): Assessment & validation of imaging modality performance across the NAFLD spectrum in a prospectively recruited cohort study (the LITMUS imaging study): Study protocol.

Non-alcoholic fatty liver disease (NAFLD) is the liver manifestation of the metabolic syndrome with global prevalence reaching epidemic levels. Despite the high disease burden in the population only a small proportion of those with NAFLD will develop progressive liver disease, for which there is currently no approved pharmacotherapy. Identifying those who are at risk of progressive NAFLD currently requires a liver biopsy which is problematic. Firstly, liver biopsy is invasive and therefore not appropriate for use in a condition like NAFLD that affects a large proportion of the population. Secondly, biopsy is limited by sampling and observer dependent variability which can lead to misclassification of disease severity. Non-invasive biomarkers are therefore needed to replace liver biopsy in the assessment of NAFLD. Our study addresses this unmet need. The LITMUS Imaging Study is a prospectively recruited multi-centre cohort study evaluating magnetic resonance imaging and elastography, and ultrasound elastography against liver histology as the reference standard. Imaging biomarkers and biopsy are acquired within a 100-day window. The study employs standardised processes for imaging data collection and analysis as well as a real time central monitoring and quality control process for all the data submitted for analysis. It is anticipated that the high-quality data generated from this study will underpin changes in clinical practice for the benefit of people with NAFLD. Study Registration: clinicaltrials.gov: NCT05479721.

COVID-19 impact assessment on the French radiological centers: a nationwide survey.

PURPOSE: To determine the impact of the COVID-19 on the CT activities in French radiological centers during the epidemic peak. MATERIALS AND METHODS: A cross-sectional prospective CT scan survey was conducted between March 16 and April 12, 2020, in accordance with the local IRB. Seven hundred nine radiology centers were invited to participate in a weekly online survey. Numbers of CT examinations related to COVID-19 including at least chest (CTcovid) and whole chest CT scan activities (CTchest) were recorded each week. A sub-analysis on French departments was performed during the 4 weeks of the study. The impact of the number of RT-PCRs (reverse transcriptase polymerase chain reactions) on the CT workflow was tested using two-sample t test and Pearson's test. RESULTS: Five hundred seventy-seven structures finally registered (78%) with mean response numbers of 336 ± 18.9 (323; 351). Mean CTchest activity per radiologic structure ranged from 75.8 ± 133 (0-1444) on week 12 to 99.3 ± 138.6 (0-1147) on week 13. Mean ratio of CTcovid on CTchest varied from 0.36 to 0.59 on week 12 and week 14 respectively. There was a significant relationship between the number of RT-PCR performed and the number of CTcovid (r = 0.73, p = 3.10-16) but no link with the number of positive RT-PCR results. CONCLUSION: In case of local high density COVID-19, CT workflow is strongly modified and redirected to the management of these specific patients. KEY POINTS: • Over the 4-week survey period, 117,686 chest CT (CTtotal) were performed among the responding centers, including 61,784 (52%) CT performed for COVID-19 (CTcovid). • Across the country, the ratio CTcovid/CTtotal varied from 0.36 to 0.59 and depended significantly on the local epidemic density (p = 0.003). • In clinical practice, in a context of growing epidemic, in France, chest CT was used as a surrogate to RT-PCR for patient triage.

Prediction of the histopathologic findings of intrahepatic cholangiocarcinoma: qualitative and quantitative assessment of diffusion-weighted imaging.

OBJECTIVE: To correlate qualitative and quantitative diffusion weighted imaging (DWI) characteristics of intrahepatic cholangiocarcinoma (ICC) with histopathologic tumour grade and fibrosis content. METHODS: Fifty-one patients (21M/30F; mean age 61y) with ICC and MRI including DWI were included in this IRB-approved multicentre retrospective study. Qualitative tumour features were assessed. Tumour apparent diffusion coefficient (ADC) mean, minimum, and normalized (nADCliver) values were computed. Tumour grade [well(G1), moderately(G2), or poorly differentiated(G3)] and tumour fibrosis content [minimal(1), moderate(2), or abundant(3)] were categorized pathologically. Imaging findings and ADC values were compared with pathologic measures. Utility of ADC values for predicting tumour grade was assessed using ROC analysis. RESULTS: 51 ICCs (mean size 6.5±1.1 cm) were assessed. 33/51(64%) of ICCs demonstrated diffuse hyperintensity and 15/51(29%) demonstrated target appearance on DWI. Infiltrative morphology (p=0.02) and tumour size (p=0.04) were associated with G3. ADCmean and nADCmean of G3 (1.32±0.47x10-3 mm2/sec and 0.97±0.95) were lower than G1+G2 (1.57±0.39x10-3 mm2/sec and 1.24±0.49; p=0.03 and p=0.04). ADCmean and nADCmean were inversely correlated with tumour grade (p<0.025). No correlation was found between ADC and tumour fibrosis content. AUROC, sensitivity and specificity of nADCmean for G3 versus G1+G2 were 0.71, 89.5% and 55.5%. CONCLUSION: ADC quantification has reasonable accuracy for predicting ICC grade. KEY POINTS: • ADC quantification was useful for predicting ICC tumour grade. • Infiltrative tumour morphology and size were associated with poorly differentiated ICCs. • ADC values depended more on ICC tumour grade than fibrosis content. • Ability to predict ICC tumour grade non-invasively could impact patient management.

Feasibility and reproducibility of liver surface nodularity quantification for the assessment of liver cirrhosis using CT and MRI.

PURPOSE: To assess intra-observer, inter-observer and inter-modality (CT vs. MRI) reproducibility of liver surface nodularity (LSN) scores measured with software used for detection of liver fibrosis. METHODS: This IRB-approved retrospective study included patients with both abdominal CT and MRI within 6 months of histopathologic sampling. Two independent observers used post-processing software to quantify LSN scores on axial non-contrast CT (NCT), axial contrast-enhanced CT (CECT), axial T2-weighted (T2W) HASTE, and axial and coronal post-gadoxetic acid T1-weighted (T1W) images obtained during the hepatobiliary phase (HBP). Ten slices were used to acquire the LSN scores. Intra-observer, inter-observer, and inter-modality (CT vs. MRI) reproducibility were assessed with intraclass correlation coefficient (ICC) and coefficients of variability (CV). Accuracy for detection of cirrhosis was evaluated for each technique. RESULTS: 26 patients (M/F 19/7, mean age 57 years), including 7 with cirrhosis (26.9%), were assessed. Technical failure occurred with NCT (1/23, 4.3%) and T2 HASTE (8/28, 28.6%). Intra-observer reproducibility was excellent for NCT, CECT, axial and coronal T1W HBP [ICC ≥ 0.92, CV ≤ 8%]. Inter-observer reproducibility was also excellent for NCT and CECT (ICC ≥ 0.95, CV ≤ 7.3%) and for coronal T1W HBP (ICC = 0.84, CV = 5.6%). There was fair to moderate agreement between CT and MRI (ICC 0.20-0.44). There were significant differences in mean LSN scores between non-cirrhotic and cirrhotic patients with NCT (2.6 vs. 4.2, p = 0.04) and T1W HBP (3.7 vs. 4.6; p = 0.01) images, with AUCs of 0.81 and 0.82, respectively. CONCLUSIONS: LSN measurement is highly reproducible with NCT and post-contrast T1W HBP on MRI, with different results obtained between CT and MRI.

Value of tumor stiffness measured with MR elastography for assessment of response of hepatocellular carcinoma to locoregional therapy.

PURPOSE: The aim of the study was to correlate tumor stiffness (TS) measured with MR elastography (MRE) with degree of tumor enhancement and necrosis on contrast-enhanced T1-weighted imaging (CE-T1WI) in hepatocellular carcinomas (HCC) treated with Yttrium-90 radioembolization (RE) or transarterial chemoembolization plus radiofrequency ablation (TACE/RFA). MATERIAL AND METHODS: This retrospective study was IRB-approved and the requirement for informed consent was waived. 52 patients (M/F 38/14, mean age 67 years) with HCC who underwent RE (n = 22) or TACE/RFA (n = 30) and 11 controls (M/F 6/5, mean age 64 years) with newly diagnosed untreated HCC were included. The MRI protocol included a 2D MRE sequence. TS and LS (liver stiffness) were measured on stiffness maps. Degree of tumor necrosis was assessed on subtraction images by two observers, and tumor enhancement ratios (ER) were calculated on CE-T1WI by one observer. RESULTS: 63 HCCs (mean size 3.2 ± 1.6 cm) were evaluated. TS was significantly lower in treated vs. untreated tumors (3.9 ± 1.8 vs. 6.9 ± 3.4 kPa, p = 0.006) and also compared to LS (5.3 ± 2.2 kPa, p = 0.002). There were significant correlations between TS and each of enhancement ratios (r = 0.514, p = 0.0001), and percentage of necrosis (r = -0.540, p = 0.0001). The observed correlations were stronger in patients treated with RE (TS vs. ER, r = 0.636, TS vs. necrosis, r = -0.711, both p = 0.0001). Percentage of necrosis and T1-signal in native T1WI were significant independent predictors of TS (p = 0.0001 and 0.001, respectively). CONCLUSION: TS measured with MRE shows a significant correlation with tumor enhancement and necrosis, especially in HCCs treated with RE.

DCE-MRI of the prostate using shutter-speed vs. Tofts model for tumor characterization and assessment of aggressiveness.

PURPOSE: To quantify Tofts model (TM) and shutter-speed model (SSM) perfusion parameters in prostate cancer (PCa) and noncancerous peripheral zone (PZ) and to compare the diagnostic performance of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) to Prostate Imaging and Reporting and Data System (PI-RADS) classification for the assessment of PCa aggressiveness. MATERIALS AND METHODS: Fifty PCa patients (mean age 60 years old) who underwent MRI at 3.0T followed by prostatectomy were included in this Institutional Review Board-approved retrospective study. DCE-MRI parameters (Ktrans , ve , kep [TM&SSM] and intracellular water molecule lifetime τi [SSM]) were determined in PCa and PZ. Differences in DCE-MRI parameters between PCa and PZ, and between models were assessed using Wilcoxon signed-rank tests. Receiver operating characteristic (ROC) analysis for differentiation between PCa and PZ was performed for individual and combined DCE-MRI parameters. Diagnostic performance of DCE-MRI parameters for identification of aggressive PCa (Gleason ≥8, grade group [GG] ≥3 or pathology stage pT3) was assessed using ROC analysis and compared with PI-RADSv2 scores. RESULTS: DCE-MRI parameters were significantly different between TM and SSM and between PZ and PCa (P < 0.037). Diagnostic performances of TM and SSM for differentiation of PCa from PZ were similar (highest AUC TM: Ktrans +kep 0.76, SSM: τi +kep 0.80). PI-RADS outperformed TM and SSM DCE-MRI for identification of Gleason ≥8 lesions (AUC PI-RADS: 0.91, highest AUC DCE-MRI: Ktrans +τi SSM 0.61, P = 0.002). The diagnostic performance of PI-RADS and DCE-MRI for identification of GG ≥3 and pT3 PCa was not significantly different (P > 0.213). CONCLUSION: SSM DCE-MRI did not increase the diagnostic performance of DCE-MRI for PCa characterization. PI-RADS outperformed both TM and SSM DCE-MRI for identification of aggressive cancer. LEVEL OF EVIDENCE: 3 Technical Efficacy: Stage 2 J. MAGN. RESON. IMAGING 2017;46:837-849.

Assessment of renal function using intravoxel incoherent motion diffusion-weighted imaging and dynamic contrast-enhanced MRI.

PURPOSE: To assess the correlation between each of intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) metrics in renal parenchyma with renal function, in a cohort of patients with chronic liver disease. MATERIALS AND METHODS: Thirty patients with liver disease underwent abdominal MRI at 1.5T, including a coronal respiratory-triggered IVIM-DWI sequence and a coronal 3D FLASH DCE-MRI acquisition. Diffusion signals in the renal cortex and medulla were fitted to the IVIM model to estimate the diffusion coefficient (D), pseudodiffusion coefficient (D*), and perfusion fraction (PF). The apparent diffusion coefficient (ADC) was calculated using all b-values. The glomerular filtration rate (GFR), cortical and medullary renal plasma flow (RPF), mean transit times (MTT) of vascular and tubular compartments and the whole kidney, were calculated from DCE-MRI data by fitting to a three-compartment model. The estimated GFR (eGFR) was calculated from serum creatinine measured 30 ± 27 days of MRI. RESULTS: ADC, PF, and RPF were significantly higher in renal cortex vs. medulla (P < 10(-5) ). DCE-MRI GFR significantly correlated with, but underestimated, eGFR (Spearman's r/P = 0.49/0.01). IVIM-DWI parameters were not significantly correlated with eGFR. DCE-MRI GFR correlated weakly with D (cortex, r/P = 0.3/0.03; medulla r/P = 0.27/0.05) and ADC (cortex r/P = 0.28/0.04; medulla r/P = 0.34/0.01). Weak correlations were observed for pooled cortical and medullar RPF with PF (r/P = 0.32/10(-3) ) and with ADC (r/P = 0.29/0.0025). Significant negative correlations were observed for vascular MTT with cortical D* (r/P = -0.38/0.004) and D*×PF (r/P = -0.34/0.01). CONCLUSION: The weak correlations between renal IVIM and DCE-MRI perfusion parameters imply that these functional measures could be complementary. J. Magn. Reson. Imaging 2016;44:317-326.

Assessment of the residual tumour of colorectal liver metastases after chemotherapy: diffusion-weighted MR magnetic resonance imaging in the peripheral and entire tumour.

OBJECTIVES: To evaluate the value of diffusion-weighted imaging (DWI) in detecting residual tumours (RTs) in colorectal liver metastases (CLMs) following chemotherapy, with a focus on tumour periphery. METHODS: From January 2009-January 2012, 57 patients who underwent liver resection for CLMs with preoperative MRI (<3 months) including DWI were retrospectively included. CLMs were classified into three response groups on pathology: (1) major histological (MHR, RTs ≤ 10 %), (2) partial histological (PHR, RT = 10-49 %), and (3) no histological (NHR, RT ≥ 50 %). On DWI, regions of interest (ROIs) were drawn around the entire tumour and tumour periphery. Apparent diffusion (ADC) and pure diffusion (D) coefficients were calculated using a monoexponential fit, and compared using Kruskal-Wallis test on a lesion-per-lesion analysis. RESULTS: 111 CLMs were included. Fourteen (12.5 %), 42 (38 %) and 55 (49.5 %) CLMs presented a MHR, PHR and NHR, respectively. ADC and D of the peripheral ROIs were significantly higher in the MHR group (P = 0.013/P = 0.013). ADC and D from the entire tumour were not significantly different among the groups (P = 0.220/P = 0.103). CONCLUSION: In CLM treated with chemotherapy, ADC and D values from the entire tumour are not related to the degree of RT, while peripheral zone diffusion parameters could help identify metastases with MHR. KEY POINTS: Peripheral ADC and D of CLMs were higher with major pathological responses. Global ADC and D of CLMs were not different according to residual tumour. Diffusion-weighted images of CLM periphery could be an interesting biomarker of MHR. Diffusion-weighted images could be used to help tailor treatment.