Precision and Test-Retest Repeatability of Stiffness Measurement with MR Elastography: A Multicenter Phantom Study.

Background MR elastography (MRE) has been shown to have excellent performance for noninvasive liver fibrosis staging. However, there is limited knowledge regarding the precision and test-retest repeatability of stiffness measurement with MRE in the multicenter setting. Purpose To determine the precision and test-retest repeatability of stiffness measurement with MRE across multiple centers using the same phantoms. Materials and Methods In this study, three cylindrical phantoms made of polyvinyl chloride gel mimicking different degrees of liver stiffness in humans (phantoms 1-3: soft, medium, and hard stiffness, respectively) were evaluated. Between January 2021 and January 2022, phantoms were circulated between five different centers and scanned with 10 MRE-equipped clinical 1.5-T and 3-T systems from three major vendors, using two-dimensional (2D) gradient-recalled echo (GRE) imaging and/or 2D spin-echo (SE) echo-planar imaging (EPI). Similar MRE acquisition parameters, hardware, and reconstruction algorithms were used at each center. Mean stiffness was measured by a single observer for each phantom and acquisition on a single section. Stiffness measurement precision and same-session test-retest repeatability were assessed using the coefficient of variation (CV) and the repeatability coefficient (RC), respectively. Results The mean precision represented by the CV was 5.8% (95% CI: 3.8, 7.7) for all phantoms and both sequences combined. For all phantoms, 2D GRE achieved a CV of 4.5% (95% CI: 3.3, 5.7) whereas 2D SE EPI achieved a CV of 7.8% (95% CI: 3.1, 12.6). The mean RC of stiffness measurement was 5.8% (95% CI: 3.7, 7.8) for all phantoms and both sequences combined, 4.9% (95% CI: 2.7, 7.0) for 2D GRE, and 7.0% (95% CI: 2.9, 11.2) for 2D SE EPI (all phantoms). Conclusion MRE had excellent in vitro precision and same-session test-retest repeatability in the multicenter setting when similar imaging protocols, hardware, and reconstruction algorithms were used. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Tang in this issue.

Characterization of renal masses with MRI-based radiomics: assessment of inter-package and inter-observer reproducibility in a prospective pilot study.

OBJECTIVES: To evaluate radiomics features' reproducibility using inter-package/inter-observer measurement analysis in renal masses (RMs) based on MRI and to employ machine learning (ML) models for RM characterization. METHODS: 32 Patients (23M/9F; age 61.8 ± 10.6 years) with RMs (25 renal cell carcinomas (RCC)/7 benign masses; mean size, 3.43 ± 1.73 cm) undergoing resection were prospectively recruited. All patients underwent 1.5 T MRI with T2-weighted (T2-WI), diffusion-weighted (DWI)/apparent diffusion coefficient (ADC), and pre-/post-contrast-enhanced T1-weighted imaging (T1-WI). RMs were manually segmented using volume of interest (VOI) on T2-WI, DWI/ADC, and T1-WI pre-/post-contrast imaging (1-min, 3-min post-injection) by two independent observers using two radiomics software packages for inter-package and inter-observer assessments of shape/histogram/texture features common to both packages (104 features; n = 26 patients). Intra-class correlation coefficients (ICCs) were calculated to assess inter-observer and inter-package reproducibility of radiomics measurements [good (ICC ≥ 0.8)/moderate (ICC = 0.5-0.8)/poor (ICC < 0.5)]. ML models were employed using reproducible features (between observers and packages, ICC > 0.8) to distinguish RCC from benign RM. RESULTS: Inter-package comparisons demonstrated that radiomics features from T1-WI-post-contrast had the highest proportion of good/moderate ICCs (54.8-58.6% for T1-WI-1 min), while most features extracted from T2-WI, T1-WI-pre-contrast, and ADC exhibited poor ICCs. Inter-observer comparisons found that radiomics measurements from T1-WI pre/post-contrast and T2-WI had the greatest proportion of features with good/moderate ICCs (95.3-99.1% T1-WI-post-contrast 1-min), while ADC measurements yielded mostly poor ICCs. ML models generated an AUC of 0.71 [95% confidence interval = 0.67-0.75] for diagnosis of RCC vs. benign RM. CONCLUSION: Radiomics features extracted from T1-WI-post-contrast demonstrated greater inter-package and inter-observer reproducibility compared to ADC, with fair accuracy for distinguishing RCC from benign RM. CLINICAL RELEVANCE: Knowledge of reproducibility of MRI radiomics features obtained on renal masses will aid in future study design and may enhance the diagnostic utility of radiomics models for renal mass characterization.

Contemporary and Emerging MRI Strategies for Assessing Kidney Allograft Complications: Arterial Stenosis and Parenchymal Injury, From the AJR Special Series on Imaging of Fibrosis.

MRI plays an important role in the evaluation of kidney allografts for vascular complications as well as parenchymal insults. Transplant renal artery stenosis, the most common vascular complication of kidney transplant, can be evaluated by MRA using gadolinium and nongadolinium contrast agents as well as by unenhanced MRA techniques. Parenchymal injury occurs through a variety of pathways, including graft rejection, acute tubular injury, BK polyomavirus infection, drug-induced interstitial nephritis, and pyelonephritis. Investigational MRI techniques have sought to differentiate among these causes of dysfunction as well as to assess the degree of interstitial fibrosis or tubular atrophy (IFTA)-the common end pathway for all of these processes-which is currently evaluated by invasively obtained core biopsies. Some of these MRI sequences have shown promise in not only assessing the cause of parenchymal injury but also assessing IFTA noninvasively. This review describes current clinically used MRI techniques and previews promising investigational MRI techniques for assessing complications of kidney grafts.

Prediction of locally advanced rectal cancer response to neoadjuvant chemoradiation therapy using volumetric multiparametric MRI-based radiomics.

PURPOSE: To assess the role of pretreatment multiparametric (mp)MRI-based radiomic features in predicting pathologic complete response (pCR) of locally advanced rectal cancer (LARC) to neoadjuvant chemoradiation therapy (nCRT). METHODS: This was a retrospective dual-center study including 98 patients (M/F 77/21, mean age 60 years) with LARC who underwent pretreatment mpMRI followed by nCRT and total mesorectal excision or watch and wait. Fifty-eight patients from institution 1 constituted the training set and 40 from institution 2 the validation set. Manual segmentation using volumes of interest was performed on T1WI pre-/post-contrast, T2WI and diffusion-weighted imaging (DWI) sequences. Demographic information and serum carcinoembryonic antigen (CEA) levels were collected. Shape, 1st and 2nd order radiomic features were extracted and entered in models based on principal component analysis used to predict pCR. The best model was obtained using a k-fold cross-validation method on the training set, and AUC, sensitivity and specificity for prediction of pCR were calculated on the validation set. RESULTS: Stage distribution was T3 (n = 79) or T4 (n = 19). Overall, 16 (16.3%) patients achieved pCR. Demographics, MRI TNM stage, and CEA were not predictive of pCR (p range 0.59-0.96), while several radiomic models achieved high diagnostic performance for prediction of pCR (in the validation set), with AUCs ranging from 0.7 to 0.9, with the best model based on high b-value DWI demonstrating AUC of 0.9 [95% confidence intervals: 0.67, 1], sensitivity of 100% [100%, 100%], and specificity of 81% [66%, 96%]. CONCLUSION: Radiomic models obtained from pre-treatment MRI show good to excellent performance for the prediction of pCR in patients with LARC, superior to clinical parameters and CEA. A larger study is needed for confirmation of these results.

Magnetic resonance elastography for noninvasive detection of liver fibrosis: is there an added value of 3D acquisition?

PURPOSE: (1) Assess the diagnostic performance of liver 3D magnetic resonance elastography (MRE) parameters (including stiffness, storage/loss modulus and damping ratio) compared to liver stiffness measured with 2D MRE for noninvasive detection of advanced liver fibrosis (F3-F4) and cirrhosis (F4) in patients with chronic liver disease. (2) Assess the value of serum markers (FIB-4) in detecting advanced liver fibrosis and cirrhosis in the same patients. METHODS: This was a single center, prospective IRB-approved cross-sectional study that included 49 patients (M/F: 23/26, mean age 50.8 y) with chronic liver disease and concomitant liver biopsy. MRE was acquired at 1.5T using a spin echo-EPI sequence. The following parameters were measured: liver stiffness using 2D MRE (LS-2D) and 3D MRE parameters (LS-3D, liver storage, loss modulus and damping ratio). The Mann-Whitney U test, ROC curve analysis, Spearman correlation and logistic regression were performed to evaluate diagnostic performance of MRE parameters and FIB-4. RESULTS: LS-2D and LS-3D had similar diagnostic performance for diagnosis of F3-F4, with AUCs of 0.87 and 0.88, sensitivity of 0.71 and 0.81, specificity of 0.89 for both. For diagnosis of F4, LS-2D and LS-3D had similar performance with AUCs of 0.81 for both, sensitivity of 0.75 and 0.83, and specificity of 0.84 and 0.73, respectively. Additional 3D parameters (storage modulus, loss modulus, damping ratio) had variable performance, with AUC range of 0.59-0.78 for F3-F4; and 0.52-0.70 for F4. FIB-4 had lower diagnostic performance, with AUCs of 0.66 for F3-F4, and 0.68 for F4. CONCLUSION: Our study shows no added value of 3D MRE compared to 2D MRE for detection of advanced fibrosis and cirrhosis, while FIB-4 had lower diagnostic performance.

Renal MRI: From Nephron to NMR Signal.

Renal diseases pose a significant socio-economic burden on healthcare systems. The development of better diagnostics and prognostics is well-recognized as a key strategy to resolve these challenges. Central to these developments are MRI biomarkers, due to their potential for monitoring of early pathophysiological changes, renal disease progression or treatment effects. The surge in renal MRI involves major cross-domain initiatives, large clinical studies, and educational programs. In parallel with these translational efforts, the need for greater (patho)physiological specificity remains, to enable engagement with clinical nephrologists and increase the associated health impact. The ISMRM 2022 Member Initiated Symposium (MIS) on renal MRI spotlighted this issue with the goal of inspiring more solutions from the ISMRM community. This work is a summary of the MIS presentations devoted to: 1) educating imaging scientists and clinicians on renal (patho)physiology and demands from clinical nephrologists, 2) elucidating the connection of MRI parameters with renal physiology, 3) presenting the current state of leading MR surrogates in assessing renal structure and functions as well as their next generation of innovation, and 4) describing the potential of these imaging markers for providing clinically meaningful renal characterization to guide or supplement clinical decision making. We hope to continue momentum of recent years and introduce new entrants to the development process, connecting (patho)physiology with (bio)physics, and conceiving new clinical applications. We envision this process to benefit from cross-disciplinary collaboration and analogous efforts in other body organs, but also to maximally leverage the unique opportunities of renal physiology. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY STAGE: 2.

Multiparametric MRI of Solid Renal Masses: Principles and Applications of Advanced Quantitative and Functional Methods for Tumor Diagnosis and Characterization.

Solid renal masses (SRMs) are increasingly detected and encompass both benign and malignant masses, with renal cell carcinoma (RCC) being the most common malignant SRM. Most patients with SRMs will undergo management without a priori pathologic confirmation. There is an unmet need to noninvasively diagnose and characterize RCCs, as significant variability in clinical behavior is observed and a wide range of differing management options exist. Cross-sectional imaging modalities, including magnetic resonance imaging (MRI), are increasingly used for SRM characterization. Multiparametric (mp) MRI techniques can provide insight into tumor biology by probing different physiologic/pathophysiologic processes noninvasively. These include sequences that probe tissue microstructure, including intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) and T1 relaxometry; oxygen metabolism (blood oxygen level dependent [BOLD-MRI]); as well as vascular flow and perfusion (dynamic contrast-enhanced MRI [DCE-MRI] and arterial spin labeling [ASL]). In this review, we will discuss each mpMRI method in terms of its principles, roles, and discuss the results of human studies for SRM assessment. Future validation of these methods may help to enable a personalized management approach for patients with SRM in the emerging era of precision medicine. EVIDENCE LEVEL: 5. TECHNICAL EFFICACY: 2.

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.

Urine supernatant reveals a signature that predicts survival in clear-cell renal cell carcinoma.

OBJECTIVE: To profile the cell-free urine supernatant and plasma of a small cohort of clear-cell renal cell carcinoma (ccRCC) patients by measuring the relative concentrations of 92 proteins related to inflammation. Using The Cancer Genome Atlas (TCGA), we then performed a targeted mRNA analysis of genes encoding the above proteins and defined their effects on overall survival (OS). SUBJECTS/PATIENTS AND METHODS: Samples were collected prospectively from ccRCC patients. A multiplex proximity extension assay was used to measure the concentrations of 92 inflammation-related proteins in cell-free urine supernatants and plasma. Transcriptomic and clinical information from ccRCC patients was obtained from TCGA. Unsupervised clustering and differential protein expression analyses were performed on protein concentration data. Targeted mRNA analysis on genes encoding significant differentially expressed proteins was performed using TCGA. Backward stepwise regression analyses were used to build a nomogram. The performance of the nomogram and clinical benefit was assessed by discrimination and calibration, and a decision curve analysis, respectively. RESULTS: Unsupervised clustering analysis revealed inflammatory signatures in the cell-free urine supernatant of ccRCC patients. Backward stepwise regressions using TCGA data identified transcriptomic risk factors and risk groups associated with OS. A nomogram to predict 2-year and 5-year OS was developed using these risk factors. The decision curve analysis showed that our model was associated with a net benefit improvement compared to the treat-all/none strategies. CONCLUSION: We defined four novel biomarkers using proteomic and transcriptomic data that distinguish severity of prognosis in ccRCC. We showed that these biomarkers can be used in a model to predict 2-year and 5-year OS in ccRCC across different tumour stages. This type of analysis, if validated in the future, provides non-invasive prognostic information that could inform either management or surveillance strategies for patients.

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.

Performance of native and gadoxetate-enhanced liver and spleen T1 mapping for noninvasive diagnosis of clinically significant portal hypertension: preliminary results.

PURPOSE: In this preliminary study, our aim was to assess the utility of quantitative native-T1 (T1-pre), iron-corrected T1 (cT1) of the liver/spleen and T1 mapping of the liver obtained during hepatobiliary phase (T1-HBP) post-gadoxetate disodium, compared to spleen size/volume and APRI (aspartate aminotransferase-to-platelet ratio index) for noninvasive diagnosis of clinically significant portal hypertension [CSPH, defined as hepatic venous pressure gradient (HVPG) ≥ 10 mm Hg]. METHODS: Forty-nine patients (M/F: 27/22, mean age 53y) with chronic liver disease, HVPG measurement and MRI were included. Breath-held T1 and cT1 measurements were obtained using an inversion recovery Look-Locker sequence and a T2* corrected modified Look-Locker sequence, respectively. Liver T1-pre (n = 49), spleen T1 (obtained pre-contrast, n = 47), liver and spleen cT1 (both obtained pre-contrast, n = 30), liver T1-HBP (obtained 20 min post gadoxetate disodium injection, n = 36) and liver T1 uptake (ΔT1, n = 36) were measured. Spleen size/volume and APRI were also obtained. Spearman correlation coefficients were used to assess the correlation between each of liver/spleen T1/cT1 parameters, spleen size/volume and APRI with HVPG. ROC analysis was performed to determine the performance of measured parameters for diagnosis of CSPH. RESULTS: There were 12/49 (24%) patients with CSPH. Liver T1-pre (r = 0.287, p = 0.045), liver T1-HBP (r = 0.543, p = 0.001), liver ΔT1 (r = - 0.437, p = 0.008), spleen T1 (r = 0.311, p = 0.033) and APRI (r = 0.394, p = 0.005) were all significantly correlated with HVPG, while liver cT1, spleen cT1 and spleen size/volume were not. The highest AUCs for the diagnosis of CSPH were achieved with liver T1-HBP, liver ΔT1 and spleen T1: 0.881 (95%CI 0.76-1.0, p = 0.001), 0.852 (0.72-0.98, p = 0.002) and 0.781 (0.60-0.95, p = 0.004), respectively. CONCLUSION: Our preliminary results demonstrate the potential of liver T1 mapping obtained during HBP post gadoxetate disodium for the diagnosis of CSPH. These results require further validation.

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.

Assessment of HCC response to Yttrium-90 radioembolization with gadoxetate disodium MRI: correlation with histopathology.

BACKGROUND AND AIMS: Transarterial 90Y radioembolization (TARE) is increasingly being used for hepatocellular carcinoma (HCC) treatment. However, tumor response assessment after TARE may be challenging. We aimed to assess the diagnostic performance of gadoxetate disodium MRI for predicting complete pathologic necrosis (CPN) of HCC treated with TARE, using histopathology as the reference standard. METHODS: This retrospective study included 48 patients (M/F: 36/12, mean age: 62 years) with HCC treated by TARE followed by surgery with gadoxetate disodium MRI within 90 days of surgery. Two radiologists evaluated tumor response using RECIST1.1, mRECIST, EASL, and LI-RADS-TR criteria and evaluated the percentage of necrosis on subtraction during late arterial, portal venous, and hepatobiliary phases (AP/PVP/HBP). Statistical analysis included inter-reader agreement, correlation between radiologic and pathologic percentage of necrosis, and prediction of CPN using logistic regression and ROC analyses. RESULTS: Histopathology demonstrated 71 HCCs (2.8 ± 1.7 cm, range: 0.5-7.5 cm) including 42 with CPN, 22 with partial necrosis, and 7 without necrosis. EASL and percentage of tumor necrosis on subtraction at the AP/PVP were independent predictors of CPN (p = 0.02-0.03). Percentage of necrosis, mRECIST, EASL, and LI-RADS-TR had fair to good performance for diagnosing CPN (AUCs: 0.78 - 0.83), with a significant difference between subtraction and LI-RADS-TR for reader 2, and in specificity between subtraction and other criteria for both readers (p-range: 0.01-0.04). Radiologic percentage of necrosis was significantly correlated to histopathologic degree of tumor necrosis (r = 0.66 - 0.8, p < 0.001). CONCLUSIONS: Percentage of tumor necrosis on subtraction and EASL criteria were significant independent predictors of CPN in HCC treated with TARE. Image subtraction should be considered for assessing HCC response to TARE when using MRI. KEY POINTS: • Percentage of tumor necrosis on image subtraction and EASL criteria are significant independent predictors of complete pathologic necrosis in hepatocellular carcinoma treated with90Y radioembolization. • Subtraction, mRECIST, EASL, and LI-RADS-TR have fair to good performance for diagnosing complete pathologic necrosis in hepatocellular carcinoma treated with90Y radioembolization.

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.

Consensus-Based Technical Recommendations for Clinical Translation of Renal Phase Contrast MRI.

BACKGROUND: Phase-contrast (PC) MRI is a feasible and valid noninvasive technique to measure renal artery blood flow, showing potential to support diagnosis and monitoring of renal diseases. However, the variability in measured renal blood flow values across studies is large, most likely due to differences in PC-MRI acquisition and processing. Standardized acquisition and processing protocols are therefore needed to minimize this variability and maximize the potential of renal PC-MRI as a clinically useful tool. PURPOSE: To build technical recommendations for the acquisition, processing, and analysis of renal 2D PC-MRI data in human subjects to promote standardization of renal blood flow measurements and facilitate the comparability of results across scanners and in multicenter clinical studies. STUDY TYPE: Systematic consensus process using a modified Delphi method. POPULATION: Not applicable. SEQUENCE FIELD/STRENGTH: Renal fast gradient echo-based 2D PC-MRI. ASSESSMENT: An international panel of 27 experts from Europe, the USA, Australia, and Japan with 6 (interquartile range 4-10) years of experience in 2D PC-MRI formulated consensus statements on renal 2D PC-MRI in two rounds of surveys. Starting from a recently published systematic review article, literature-based and data-driven statements regarding patient preparation, hardware, acquisition protocol, analysis steps, and data reporting were formulated. STATISTICAL TESTS: Consensus was defined as ≥75% unanimity in response, and a clear preference was defined as 60-74% agreement among the experts. RESULTS: Among 60 statements, 57 (95%) achieved consensus after the second-round survey, while the remaining three showed a clear preference. Consensus statements resulted in specific recommendations for subject preparation, 2D renal PC-MRI data acquisition, processing, and reporting. DATA CONCLUSION: These recommendations might promote a widespread adoption of renal PC-MRI, and may help foster the set-up of multicenter studies aimed at defining reference values and building larger and more definitive evidence, and will facilitate clinical translation of PC-MRI. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY STAGE: 1.

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.

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.

Emerging Imaging Biomarkers in Crohn Disease.

ABSTRACT: In this review article, we present the latest developments in quantitative imaging biomarkers based on magnetic resonance imaging (MRI), applied to the diagnosis, assessment of response to therapy, and assessment of prognosis of Crohn disease. We also discuss the biomarkers' limitations and future prospects. We performed a literature search of clinical and translational research in Crohn disease using diffusion-weighted MRI (DWI-MRI), dynamic contrast-enhanced MRI (DCE-MRI), motility MRI, and magnetization transfer MRI, as well as emerging topics such as T1 mapping, radiomics, and artificial intelligence. These techniques are integrated in and combined with qualitative image assessment of magnetic resonance enterography (MRE) examinations. Quantitative MRI biomarkers add value to MRE qualitative assessment, achieving substantial diagnostic performance (area under receiver-operating curve = 0.8-0.95). The studies reviewed show that the combination of multiple MRI sequences in a multiparametric quantitative fashion provides rich information that may help for better diagnosis, assessment of severity, prognostication, and assessment of response to biological treatment. However, the addition of quantitative sequences to MRE examinations has potential drawbacks, including increased scan time and the need for further validation before being used in therapeutic drug trials as well as the clinic.

Early effect of 90Y radioembolisation on hepatocellular carcinoma and liver parenchyma stiffness measured with MR elastography: initial experience.

OBJECTIVES: To quantify hepatocellular carcinoma (HCC) and liver parenchyma stiffness using MR elastography (MRE) and serum alpha fetoprotein (AFP), before and 6 weeks (6w) after 90Y radioembolisation (RE), and to assess the value of baseline tumour and liver stiffness (TS/LS) and AFP in predicting response at 6w and 6 months (6 m). METHODS: Twenty-three patients (M/F 18/5, mean age 68.3 ± 9.3 years) scheduled to undergo RE were recruited into this prospective single-centre study. Patients underwent an MRI exam at baseline and 6w following RE (range 39-47 days) which included MRE using a prototype 2D EPI sequence. TS, peritumoural LS/LS remote from the tumour, tumour size, and AFP were measured at baseline and at 6w. Treatment response was determined using mRECIST at 6w and 6 m. RESULTS: MRE was technically successful in 17 tumours which were classified at 6w as complete response (CR, n = 7), partial response (PR, n = 4), and stable disease (SD, n = 6). TS and peritumoural LS were significantly increased following RE (p = 0.016, p = 0.039, respectively), while LS remote from tumour was unchanged (p = 0.245). Baseline TS was significantly lower in patients who achieved CR at 6w (p = 0.014). Baseline TS, peritumoural LS (both AUC = 0.857), and AFP (AUC = 0.798) showed fair/excellent diagnostic performance in predicting CR at 6w, but were not significant predictors of OR or CR at 6 m. CONCLUSION: Our initial results suggest that HCC TS and peritumoural LS increase early after RE. Baseline TS, peritumoural LS, and AFP were all significant predictors of CR to RE at 6w. These results should be confirmed in a larger study. KEY POINTS: • Magnetic resonance elastography-derived tumour stiffness and peritumoural liver stiffness increase significantly at 6 weeks post radioembolisation whereas liver stiffness remote from the tumour is unchanged. • Baseline tumour stiffness and peritumoural liver stiffness are lower in patients who achieve complete response at 6 weeks post radioembolisation. • Baseline tumour size is significantly correlated with baseline tumour stiffness.

MRI Mapping of Renal T1: Basic Concept.

In renal MRI, measurement of the T1 relaxation time of water molecules may provide a valuable biomarker for a variety of pathological conditions. Due to its sensitivity to the tissue microenvironment, T1 has gained substantial interest for noninvasive imaging of renal pathology, including inflammation and fibrosis. In this chapter, we will discuss the basic concept of T1 mapping and different T1 measurement techniques and we will provide an overview of emerging preclinical applications of T1 for imaging of kidney disease.This chapter is based upon work from the COST Action PARENCHIMA, a community-driven network funded by the European Cooperation in Science and Technology (COST) program of the European Union, which aims to improve the reproducibility and standardization of renal MRI biomarkers. This introduction chapter is complemented by two separate chapters describing the experimental procedure and data analysis.