Prospective head-to-head comparison of non-invasive scores for diagnosis of fibrotic MASH in patients with type 2 diabetes.

BACKGROUND & AIMS: Non-invasive scores have been proposed to identify patients with fibrotic, metabolic dysfunction-associated steatohepatitis (MASH), who are at the highest risk of progression to complications of cirrhosis and may benefit from pharmacologic treatments. However, data in patients with type 2 diabetes (T2DM) are lacking. The aim of this multicenter prospective study was to perform a head-to-head comparison of FAST (FibroScan-aspartate aminotransferase [AST]), MAST (MRI-AST), MEFIB (magnetic resonance elastography [MRE] plus FIB-4), and FNI (fibrotic NASH index) for detecting fibrotic MASH in patients with T2DM. METHODS: A total of 330 outpatients with T2DM and biopsy-proven metabolic dysfunction-associated steatotic liver disease (MASLD) from the QUID-NASH study (NCT03634098), who underwent FibroScan, MRI-proton density fat fraction and MRE at the time of liver biopsy were studied. The main outcome was fibrotic MASH, defined as NAS ≥4 (with at least one point for each parameter) and fibrosis stage ≥2 (centrally reviewed). RESULTS: All data for score comparisons were available for 245 patients (median age 59 years, 65% male, median BMI 31 kg/m2; fibrotic MASH in 39%). FAST and MAST had similar accuracy (AUROCs 0.81 vs. 0.79, p = 0.41) but outperformed FNI (0.74; p = 0.01) and MEFIB (0.68; p <0.0001). When using original cut-offs, MAST outperformed FAST, MEFIB and FNI when comparing the percentage of correctly classified patients, in whom liver biopsy would be avoided (69% vs. 48%, 46%, 39%, respectively; p <0.001). When using cut-offs specific to our population, FAST outperformed FNI and MAST (56% vs. 40%, and 38%, respectively; p <0.001). CONCLUSION: Our findings show that FAST, MAST, MEFIB and FNI are accurate non-invasive tools to identify patients with T2DM and fibrotic MASH in secondary/tertiary diabetes clinics. Cut-offs adapted to the T2DM population should be considered. IMPACT AND IMPLICATIONS: Among patients with type 2 diabetes (T2DM), identifying those with metabolic dysfunction-associated steatohepatitis and significant fibrosis, who are the most at risk of developing clinical liver-related outcomes and who may benefit from pharmacologic treatments, is an unmet need. In this prospective multicenter study, we compared four non-invasive scores, three based on imaging (MRI or ultrasound technologies) and one on laboratory blood tests, for this purpose, using original and study-specific cut-offs. Our findings show that FAST, MAST, MEFIB and FNI are accurate non-invasive tools to identify patients with T2DM and fibrotic MASH in secondary/tertiary diabetes clinics. Cut-offs adapted to the T2DM population should be considered. TRIAL REGISTRATION NUMBER: NCT03634098.

Visco-Elastic Parameters at Three-Dimensional MR Elastography for Diagnosing Non-Alcoholic Steatohepatitis and Substantial Fibrosis in Mice.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is increasing worldwide and is a growing cause of liver cirrhosis and cancer. The performance of the magnetic resonance elastography (MRE) visco-elastic parameters in diagnosing progressive forms of NAFLD, including nonalcoholic steatohepatitis (NASH) and substantial fibrosis (F ≥ 2), needs to be clarified. PURPOSE: To assess the value of three-dimensional MRE visco-elastic parameters as markers of NASH and substantial fibrosis in mice with NAFLD. STUDY TYPE: Prospective. ANIMAL MODEL: Two mouse models of NAFLD were induced by feeding with high fat diet or high fat, choline-deficient, amino acid-defined diet. FIELD STRENGTH/SEQUENCE: 7T/multi-slice multi-echo spin-echo MRE at 400 Hz with motion encoding in the three spatial directions. ASSESSMENT: Hepatic storage and loss moduli were calculated. Histological analysis was based on the NASH Clinical Research Network criteria. STATISTICAL TESTS: Mann-Whitney, Kruskal-Wallis tests, Spearman rank correlations and multiple regressions were used. Diagnostic performance was assessed with areas under the receiver operating characteristic curves (AUCs). P value <0.05 was considered significant. RESULTS: Among the 59 mice with NAFLD, 21 had NASH and 20 had substantial fibrosis (including 8 mice without and 12 mice with NASH). The storage and loss moduli had similar moderate accuracy for diagnosing NASH with AUCs of 0.67 and 0.66, respectively. For diagnosing substantial fibrosis, the AUC of the storage modulus was 0.73 and the AUC of the loss modulus was 0.81, indicating good diagnostic performance. Using Spearman correlations, histological fibrosis, inflammation and steatosis, but not ballooning, were significantly correlated with the visco-elastic parameters. Using multiple regression, fibrosis was the only histological feature independently associated with the visco-elastic parameters. CONCLUSION: MRE in mice with NAFLD suggests that the storage and loss moduli have good diagnostic performance for detecting progressive NAFLD defined as substantial fibrosis rather than NASH. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY STAGE: 2.

Hepatocellular carcinoma in patients with non-alcoholic fatty liver disease is associated with heterogeneous pattern of fat infiltration in skeletal muscles.

OBJECTIVES: To evaluate the association between fat infiltration in skeletal muscles (myosteatosis) and hepatocellular carcinoma (HCC) in patients with non-alcoholic fatty liver disease (NAFLD). METHODS: In a cross-sectional cohort of 72 histologically proven NAFLD patients (n = 38 with non-alcoholic steatohepatitis; NASH), among which 20 had HCC diagnosed on biopsy, we used proton density fat fraction (PDFF) at MRI to evaluate myosteatosis in skeletal muscles (mean fat fraction and first order radiomic-based pattern) at the third lumbar level, namely in erector spinae (ES), quadratus lumborum (QL), psoas, oblique, and rectus muscles. RESULTS: PDFFES was 70% higher in patients with HCC when compared to those without HCC (9.6 ± 5.5% versus 5.7 ± 3.0%, respectively, p < 0.001). In multivariate logistic regression, PDFFES was a significant predictor of the presence of HCC (AUC = 0.72, 95% CI 0.57-0.86, p = 0.002) independently from age, sex, visceral fat area, and liver fibrosis stage (all p < 0.05). The relationship between PDFFES and HCC was exacerbated in patients with NASH (AUC = 0.79, 95% CI 0.63-0.86, p = 0.006). In patients with NASH, radiomics features of heterogeneity such as energy and entropy in any of the paraspinal muscles (i.e., ES, QL, or psoas) were independent predictors of HCC. EnergyES identified patients with HCC (n = 13) in the NASH population with AUC = 0.92 (95% CI 0.82-1.00, p < 0.001). CONCLUSION: In patients with NAFLD, and more specifically in those with NASH, the degree and heterogeneity of myosteatosis is independently associated with HCC irrespective of liver fibrosis stage. CLINICAL RELEVANCE STATEMENT: Our data suggest that myosteatosis could be used as a biomarker of HCC in the ever-expanding NAFLD population and pave the way for further investigation in longitudinal studies. KEY POINTS: • HCC in patients with non-alcoholic fatty liver disease, and more specifically in those with non-alcoholic steatohepatitis, is independently associated with severe fatty infiltration (myosteatosis) of paravertebral skeletal muscles. • Association between myosteatosis and HCC is independent from liver fibrosis stage. • Histogram-based radiomics features of myosteatosis predicts the risk of HCC in patients with non-alcoholic steatohepatitis.

Prospective Comparison of Attenuation Imaging and Controlled Attenuation Parameter for Liver Steatosis Diagnosis in Patients With Nonalcoholic Fatty Liver Disease and Type 2 Diabetes.

BACKGROUND & AIMS: Similarly to the controlled attenuation parameter (CAP), the ultrasound-based attenuation imaging (ATI) can quantify hepatic steatosis. We prospectively compared the performance of ATI and CAP for the diagnosis of hepatic steatosis in patients with type 2 diabetes and nonalcoholic fatty liver disease using histology and magnetic resonance imaging-proton density fat fraction (MRI-PDFF) as references. METHODS: Patients underwent ATI and CAP measurement, MRI, and biopsy on the same day. Steatosis was classified as S0, S1, S2, and S3 on histology (<5%, 5%-33%, 33%-66%, and >66%, respectively) while the thresholds of 6.4%, 17.4%, and 22.1%, respectively, were used for MRI-PDFF. The area under the curve (AUC) of ATI and CAP was compared using a DeLong test. RESULTS: Steatosis could be evaluated in 191 and 187 patients with MRI-PDFF and liver biopsy, respectively. For MRI-PDFF steatosis, the AUC of ATI and CAP were 0.86 (95% confidence interval [CI], 0.81-0.91) vs 0.69 (95% CI, 0.62-0.75) for S0 vs S1-S3 (P = .02) and 0.71 (95% CI, 0.64-0.77) vs 0.69 (95% CI, 0.61-0.75) for S0-S1 vs S2-S3 (P = .60), respectively. For histological steatosis, the AUC of ATI and CAP were 0.92 (95% CI, 0.87-0.95) vs 0.95 (95% CI, 0.91-0.98) for S0 vs S1-S3 (P = .64) and 0.79 (95% CI, 0.72-0.84) vs 0.76 (95% CI, 0.69-0.82) for S0-S1 vs S2-S3 (P = .61), respectively. CONCLUSION: ATI may be used as an alternative to CAP for the diagnosis and quantification of steatosis, in patients with type 2 diabetes and nonalcoholic fatty liver disease.

Comparative Analysis of a Locally Resampling MR Elastography Reconstruction Algorithm in Liver Fibrosis.

BACKGROUND: In magnetic resonance elastography (MRE), the precision of the observed mechanical depends on the ratio between mechanical wavelength and spatial resolution. Since the mechanical wavelength may vary with actuation frequency, between patients and depending on position, a unique spatial resolution may not always generate an optimal ratio for multifrequency acquisitions, in patients with varying degrees of disease or in mechanically heterogeneous organs. PURPOSE: To describe an MRE reconstruction algorithm that adjusts the ratio between shear wavelength and pixel size, by locally resampling the matrix of shear displacement, and to assess its performance relative to existing reconstructions in different use cases. STUDY TYPE: Prospective. POPULATION: Four phantoms, 20 healthy volunteers (5 men, median age 34, range 20-56) and 46 patients with nonalcoholic fatty liver disease (37 men, median age 63, range 33-83). FIELD STRENGTH/SEQUENCE: A 3 T; gradient-echo elastography sequence with 40 Hz, 60 Hz, and 80 Hz frequencies. ASSESSMENT: For each algorithm, phantoms stiffness were compared against their nominal values, repeatability was calculated in healthy volunteers, and diagnostic performance in detecting advanced liver fibrosis was assessed in 46 patients. STATISTICAL TESTS: Linear regression was used to evaluate the agreement between stiffness values and phantoms stiffnesses. Bland-Altman method was used to evaluate repeatability in volunteers. The ability to diagnose advanced fibrosis was assessed by receiver operating curve analysis (with Youden index thresholds). Significance was considered at P value of 0.05. RESULTS: From the linear regression, the slope closest to 1 is provided by MARS (40 Hz) and k-MDEV (60H, 80 Hz). Repeatability index was best with MDEV (23%) and lowest with k-MDEV (53%). The best performance in detecting advanced fibrosis was provided by MARS at 40 Hz (area under the operating curve, AUC = 0.88), k-MDEV and MARS at 60 Hz (AUC = 0.91), and multimodel direct inversion (MMDI) and MARS at 80 Hz (AUC = 0.90). DATA CONCLUSION: MARS shows the best diagnostic performance to detect advanced fibrosis and the second-best results in phantoms after k-MDEV. EVIDENCE LEVEL: 1. TECHNICAL EFFICACY: Stage 2.

Magnetic resonance elastography with guided pressure waves.

Magnetic resonance elastography aims to non-invasively and remotely characterize the mechanical properties of living tissues. To quantitatively and regionally map the shear viscoelastic moduli in vivo, the technique must achieve proper mechanical excitation throughout the targeted tissues. Although it is straightforward, ante manibus, in close organs such as the liver or the breast, which practitioners clinically palpate already, it is somewhat fortunately highly challenging to trick the natural protective barriers of remote organs such as the brain. So far, mechanical waves have been induced in the latter by shaking the surrounding cranial bones. Here, the skull was circumvented by guiding pressure waves inside the subject's buccal cavity so mechanical waves could propagate from within through the brainstem up to the brain. Repeatable, reproducible and robust displacement fields were recorded in phantoms and in vivo by magnetic resonance elastography with guided pressure waves such that quantitative mechanical outcomes were extracted in the human brain.

Multifrequency magnetic resonance elastography for elasticity quantitation and optimal tissue discrimination: A two-platform liver fibrosis mimicking phantom study.

In the framework of algebraic inversion, magnetic resonance elastography (MRE) repeatability, reproducibility and robustness were evaluated on extracted shear velocities (or elastic moduli). The same excitation system was implemented at two sites equipped with clinical MR scanners of 1.5 and 3 T. A set of four elastic, isotropic, homogeneous calibrated phantoms of distinct elasticity representing the spectrum of liver fibrosis severity was mechanically characterized. The repeatability of the measurements and the reproducibility between the two platforms were found to be excellent with mean coefficients of variations of 1.62% for the shear velocity mean values and 1.95% for the associated standard deviations. MRE velocities were robust to the amplitude and pattern variations of the displacement field with virtually no difference between outcomes from both magnets at identical excitation frequencies, even when the displacement field amplitude was six times smaller. However, MRE outcomes were very sensitive to the number of voxels per wavelength, s, of the recorded displacement field, with relative biases reaching 62% and precision loss by a factor of up to 23.5. For both magnetic field strengths, MRE accuracy and precision were largely degraded outside of established conditions of validity (6 ≲ s ≲ 9), resulting in estimated shear velocity values not significantly different between phantoms of increasing elasticity. When fulfilling the spatial sampling conditions, either prospectively in the acquisition or retrospectively before the reconstruction, MRE produced quantitative measurements that allowed to unambiguously discriminate, with infinitesimal p values, between the phantoms mimicking increasing severity of liver fibrosis.

Comparison of pulsed and oscillating gradient diffusion-weighted MRI for characterizing hepatocellular nodules in liver cirrhosis: ex vivo study in a rat model.

BACKGROUND: In contrast to classical pulsed gradient diffusion-weighted MRI, oscillating gradient diffusion-weighted MR imaging (DWI) is sensitive to short distance diffusion changes at the intracellular level. PURPOSE: To compare the diagnostic performance of pulsed and oscillating DWI for characterizing hepatocellular nodules in a rat model of hepatic cirrhosis. STUDY TYPE: Prospective, experimental study. ANIMAL MODEL: Cirrhosis was induced by weekly intraperitoneal injection of diethylnitrosamine in Wistar rats. FIELD STRENGTH/SEQUENCE: Ex vivo liver MRI was performed at 7T with T1 -weighted, T2 -weighted, pulsed, and oscillating gradient diffusion-weighted sequences. ASSESSMENT: Apparent diffusion coefficient from pulsed (ADCpulsed ) and oscillating gradient (ADCoscillating ) sequences was calculated in 82 nodules identified on the T1 /T2 -weighted images and on pathological examination. Two pathologists classified the nodules in three categories: benign (regenerative and low-grade dysplastic nodules), with intermediate malignancy (high-grade dysplastic nodules and early hepatocellular carcinomas) and overtly malignant (progressed hepatocellular carcinomas). STATISTICAL TESTS: Differences between groups were assessed with Kruskal-Wallis and Mann-Whitney tests. RESULTS: ADC, mainly ADCoscillating , increased in the group of nodules with intermediate malignancy (ADCpulsed : 0.75 ± 0.25 × 10-3 mm2 /s vs. 0.64 ± 0.07 × 10-3 mm2 /s in benign nodules, P = 0.025; ADCoscillating : 0.81 ± 0.20 × 10-3 mm2 /s vs. 0.65 ± 0.13 × 10-3 mm2 /s, P = 0.0008) and ADCpulsed decreased in the group of progressed hepatocellular carcinomas (ADCpulsed : 0.60 ± 0.08 × 10-3 mm2 /s, P = 0.042; ADCoscillating : 0.68 ± 0.08 × 10-3 mm2 /s, P = 0.1). DATA CONCLUSION: ADC during hepatocarcinogenesis in rats increased in nodules with intermediate malignancy and decreased in progressed hepatocellular carcinomas. Our results suggest that oscillating gradient DWI is more sensitive to the early steps of hepatocarcinogenesis and might be useful for differentiating between high-grade dysplastic nodules / early hepatocellular carcinomas and regenerating nodules / low-grade dysplastic nodules. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2020;51:1065-1074.

Quantification of hepatic steatosis with ultrasound: promising role of attenuation imaging coefficient in a biopsy-proven cohort.

OBJECTIVES: To prospectively assess the role of the US attenuation imaging coefficient (AC) for the diagnosis and quantification of hepatic steatosis. METHODS: One hundred and one patients underwent liver biopsy and US-AC measurement on the same day. Liver steatosis was graded according to biopsy as absent (S0 < 5%), mild (S1 5-33%), moderate (S2 33-66%), or severe (S3 > 66%); liver fibrosis was graded from F0 to F4. The correlation between AC and steatosis on pathology (%) was calculated using the Pearson correlation coefficient. The Student t or Mann-Whitney U test was used to compare continuous variables and ROC curve analysis was used to assess diagnostic performance of AC in diagnosing steatosis. RESULTS: Overall, 43 (42%), 35 (35%), 12 (12%), and 11 (11%) patients were classified as S0, S1, S2, and S3, respectively. The AC was positively correlated with steatosis as a continuous variable (%) on pathology (r = 0.58, p < 0.01). Patients with steatosis of any grade had a higher AC than those without steatosis (mean 0.77 ± 0.13 vs. 0.63 ± 0.09 dB/cm/MHz, respectively; p < 0.01, AUROC = 0.805). Patients with S2-S3 had a higher AC than patients with S0-1 (0.85 ± 0.11 vs. 0.67 ± 0.11 dB/cm/MHz, respectively; p < 0.01, AUROC = 0.892). AC > 0.69 dB/cm/MHz had a sensitivity and specificity of 76% and 86%, respectively, for diagnosing any grade of steatosis (S1-S3), and AC > 0.72 dB/cm/MHz had a sensitivity and specificity of 96% and 74%, respectively, for diagnosing S2-S3. The presence of advanced fibrosis (F3-F4) did not affect the calculated AC. CONCLUSIONS: The attenuation imaging coefficient is a promising quantitative technique for the non-invasive diagnosis and quantification of hepatic steatosis. KEY POINTS: • Measurement of the attenuation coefficient is achieved with a very high rate of technical success. • We found a significant positive correlation between the attenuation coefficient and the grade of steatosis on pathology. • The attenuation imaging coefficient is a promising quantitative technique for the noninvasive diagnosis and quantification of hepatic steatosis.

Assessing Tumor Mechanics by MR Elastography at Different Strain Levels.

BACKGROUND: Malignant tumors are associated with increased tissue rigidity, which can be an indicator of tumor progression. MR elastography (MRE) has the potential to study the variations of tumor mechanical properties. ex vivo studies have shown the ability of MRE to assess increase of mechanical properties; nevertheless, it has not yet been observed in vivo. PURPOSE: To propose a method to assess the increase in mechanical properties of tumors in vivo under static external compression using MRE. STUDY TYPE: Prospective, experimental study. ANIMAL MODEL: Forty-six SCID mice with subcutaneous tumor implantation (patient-derived hepatocellular carcinoma xenografts, Model 1, n = 13, and Model 2, n = 33). FIELD STRENGTH/SEQUENCE: 7.0T; a spin echo sequence was used for anatomical images and a modified spin echo sequence for elastography acquisitions with a vibration frequency of 600 Hz. ASSESSMENT: An inflatable balloon was placed on the abdomen to apply a load to the tumor. MRE acquisitions were performed at the basal state and at increasing compression levels. Anatomical images were used to calculate the octahedral shear strain between the tumor at the basal strain state and each strain level. For six mice (Model 2), each static preloading scan was acquired twice consecutively without moving the mouse to evaluate repeatability. Statistical Tests: The Bland-Altman method was used to assess repeatability. Correlations between tumor stiffness and deformation were evaluated with Pearson correlation coefficients. RESULTS: For stiffness (G*), a good repeatability was obtained between the acquisitions; the limits of agreement of the Bland-Altman test were [-10.17%; 11.49%] with an absolute bias of 0.66%. A significant correlation between tumor stiffness and deformation was observed for both models (Model 1: r = 0.57, P < 0.0001 and Model 2: r = 0.31, P < 0.0001). DATA CONCLUSION: We establish that tumor mechanical properties can increase under mechanical compression. This increase can effectively be monitored using a proposed MRE setup. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2019;50:1982-1989.

In vitro distinction between proinflammatory and antiinflammatory macrophages with gadolinium-liposomes and ultrasmall superparamagnetic iron oxide particles at 3.0T.

BACKGROUND: Inflammation involves a heterogeneous macrophage population, for which there is no readily available MR assessment method. PURPOSE: To assess the feasibility of distinguishing proinflammatory M1 and antiinflammatory M2 macrophages at MRI enhanced with gadolinium liposomes or ultrasmall superparamagnetic iron oxide particles. STUDY TYPE: In vitro. SPECIMEN: We employed cultured RAW macrophages. M0 macrophages were polarized with lipopolysaccharide (LPS) or interleukin-4 (IL-4), resulting in M1 or M2 macrophages. The macrophages were incubated with gadolinium (±rhodamine) liposomes or iron oxide particles and cell pellets were prepared for MRI. FIELD STRENGTH/SEQUENCE: Transverse relaxation rates and quantitative susceptibility were obtained at 3.0T with multiecho turbo spin echo and spoiled gradient echo sequences. ASSESSMENT: MRI results were compared with confocal microscopy, flow cytometry, and expression of endocytosis, M1 and M2 genes. STATISTICAL TESTS: Mann-Whitney and Kruskal-Wallis tests were performed. RESULTS: Higher transverse relaxation rates and susceptibility were observed in M1 than in M2 and M0 macrophages (P < 0.01 both with liposomes and USPIO) and significantly different susceptibility in M2 and M0 macrophages (P < 0.01 both with liposomes and USPIO). These MRI results were confirmed at confocal microscopy and flow cytometry. LPS macrophages displayed M1 gene expression, whereas IL-4 macrophages showed M2 polarization and lower endocytosis gene expression rates. DATA CONCLUSION: These in vitro results show that it is feasible to distinguish between proinflammatory M1 and antiinflammatory M2 macrophages according to their level of contrast agent uptake at MRI. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2019;49:1166-1173.

Magnetic resonance elastography of liver and spleen: Methods and applications.

The viscoelastic properties of the liver and spleen can be assessed with magnetic resonance elastography (MRE). Several actuators, MRI acquisition sequences and reconstruction algorithms have been proposed for this purpose. Reproducible results are obtained, especially when the examination is performed in standard conditions with the patient fasting. Accurate staging of liver fibrosis can be obtained by measuring liver stiffness or elasticity with MRE. Moreover, emerging evidence shows that assessing the tissue viscous parameters with MRE is useful for characterizing liver inflammation, non-alcoholic steatohepatitis, hepatic congestion, portal hypertension, and hepatic tumors. Further advances such as multifrequency acquisitions and compression-sensitive MRE may provide novel quantitative markers of hepatic and splenic mechanical properties that may improve the diagnosis of hepatic and splenic diseases.

Quantitative MRI in murine radiation-induced rectocolitis: comparison with histopathological inflammation score.

Murine radiation-induced rectocolitis is considered to be a relevant animal model of gastrointestinal inflammation. The purpose of our study was to compare quantitative MRI and histopathological features in this gastrointestinal inflammation model. Radiation rectocolitis was induced by localized single-dose radiation (27 Gy) in Sprague-Dawley rats. T2 -weighted, T1 -weighted and diffusion-weighted MRI was performed at 7 T in 16 rats between 2 and 4 weeks after irradiation and in 10 control rats. Rats were sacrificed and the histopathological inflammation score of the colorectal samples was assessed. The irradiated rats showed significant increase in colorectal wall thickness (2.1 ± 0.3 mm versus 0.8 ± 0.3 mm in control rats, P < 0.0001), normalized T2 signal intensity (4 ± 0.8 versus 2 ± 0.4 AU, P < 0.0001), normalized T1 signal intensity (1.4 ± 0.1 versus 1.1 ± 0.2 AU, P = 0.0009) and apparent and pure diffusion coefficients (ADC and D) (2.06 × 10-3 ± 0.34 versus 1.51 × 10-3 ± 0.23 mm2 /s, P = 0.0004, and 1.97 × 10-3 ± 0.43 mm2 /s versus 1.48 × 10-3 ± 0.29 mm2 /s, P = 0.008, respectively). Colorectal wall thickness (r = 0.84, P < 0.0001), normalized T2 signal intensity (r = 0.85, P < 0.0001) and ADC (r = 0.80, P < 0.0001) were strongly correlated with the histopathological inflammation score, whereas normalized T1 signal intensity and D were moderately correlated (r = 0.64, P = 0.0006, and r = 0.65, P = 0.0003, respectively). High-field MRI features of single-dose radiation-induced rectocolitis in rats differ significantly from those of control rats. Quantitative MRI characteristics, especially wall thickness, normalized T2 signal intensity, ADC and D, are potential markers of the histopathological inflammation score.

Hepatic Fibrosis, Inflammation, and Steatosis: Influence on the MR Viscoelastic and Diffusion Parameters in Patients with Chronic Liver Disease.

Purpose To determine the relationship of liver fibrosis, inflammation, and steatosis with the magnetic resonance (MR) viscoelastic and diffusion parameters in patients with chronic liver disease and to compare the diagnostic accuracy of the imaging parameters in staging liver fibrosis. Materials and Methods Consecutive patients with chronic liver disease scheduled for liver biopsy were prospectively recruited from November 2010 to October 2012 for this institutional review board-approved study after they provided written informed consent. Sixty-eight patients underwent three-dimensional MR elastography and intravoxel incoherent motion diffusion-weighted MR imaging with a 1.5-T MR system. Fibrosis, inflammation, and steatosis were assessed with the METAVIR and steatosis, activity, and fibrosis (or SAF) scoring systems. Spearman correlation and multiple regression analyses were performed to determine the relationship between liver fibrosis, inflammation, steatosis, and alanine aminotransferase (ALT) levels and viscoelastic and diffusion parameters. The accuracy of three-dimensional MR elastography and diffusion-weighted MR imaging in the determination of fibrosis stage was assessed with Obuchowski measures. Results At multiple regression analysis, fibrosis was the only variable associated with viscoelastic parameters (ß = 0.6, P < .001, R2 = 0.33 for shear modulus; ß = 0.6, P < .001, R2 = 0.32 for elasticity). Fibrosis had a weaker independent association with the apparent diffusion coefficient (ß = -0.3, P = .02, R2 = 0.33) than did steatosis (ß = -0.5, P < .001, R2 = 0.33). Steatosis was the only factor independently associated with the pure diffusion coefficient (ß = -0.4, P = .002, R2 = 0.22). Inflammation and ALT level were not associated with the viscoelastic or diffusion parameters. The diagnostic accuracy of fibrosis staging was significantly higher when measuring the shear modulus rather than the apparent diffusion coefficient (Obuchowski measures, 0.82 ± 0.04 vs 0.30 ± 0.06; P < .001). Conclusion Fibrosis is independently associated with the MR viscoelastic parameters and is less associated with the diffusion parameters than is steatosis. These results and those of diagnostic accuracy suggest that MR elastography should be preferred over diffusion-weighted MR imaging in the staging of liver fibrosis. © RSNA, 2016.

New imaging techniques for liver diseases.

Newly developed or advanced methods of ultrasonography and MR imaging provide combined anatomical and quantitative functional information about diffuse and focal liver diseases. Ultrasound elastography has a central role for staging liver fibrosis and an increasing role in grading portal hypertension; dynamic contrast-enhanced ultrasonography may improve tumor characterization. In clinical practice, MR imaging examinations currently include diffusion-weighted and dynamic MR imaging, enhanced with extracellular or hepatobiliary contrast agents. Moreover, quantitative parameters obtained with diffusion-weighted MR imaging, dynamic contrast-enhanced MR imaging and MR elastography have the potential to characterize further diffuse and focal liver diseases, by adding information about tissue cellularity, perfusion, hepatocyte transport function and visco-elasticity. The multiparametric capability of ultrasonography and more markedly of MR imaging gives the opportunity for high diagnostic performance by combining imaging biomarkers. However, image acquisition and post-processing methods should be further standardized and validated in multicenter trials.

Apparent diffusion coefficient is highly reproducible on preclinical imaging systems: Evidence from a seven-center multivendor study.

PURPOSE: To evaluate between-site agreement of apparent diffusion coefficient (ADC) measurements in preclinical magnetic resonance imaging (MRI) systems. MATERIALS AND METHODS: A miniaturized thermally stable ice-water phantom was devised. ADC (mean and interquartile range) was measured over several days, on 4.7T, 7T, and 9.4T Bruker, Agilent, and Magnex small-animal MRI systems using a common protocol across seven sites. Day-to-day repeatability was expressed as percent variation of mean ADC between acquisitions. Cross-site reproducibility was expressed as 1.96 × standard deviation of percent deviation of ADC values. RESULTS: ADC measurements were equivalent across all seven sites with a cross-site ADC reproducibility of 6.3%. Mean day-to-day repeatability of ADC measurements was 2.3%, and no site was identified as presenting different measurements than others (analysis of variance [ANOVA] P = 0.02, post-hoc test n.s.). Between-slice ADC variability was negligible and similar between sites (P = 0.15). Mean within-region-of-interest ADC variability was 5.5%, with one site presenting a significantly greater variation than the others (P = 0.0013). CONCLUSION: Absolute ADC values in preclinical studies are comparable between sites and equipment, provided standardized protocols are employed.

Demyelination reduces brain parenchymal stiffness quantified in vivo by magnetic resonance elastography.

The detection of pathological tissue alterations by manual palpation is a simple but essential diagnostic tool, which has been applied by physicians since the beginnings of medicine. Recently, the virtual "palpation" of the brain has become feasible using magnetic resonance elastography, which quantifies biomechanical properties of the brain parenchyma by analyzing the propagation of externally elicited shear waves. However, the precise molecular and cellular patterns underlying changes of viscoelasticity measured by magnetic resonance elastography have not been investigated up to date. We assessed changes of viscoelasticity in a murine model of multiple sclerosis, inducing reversible demyelination by feeding the copper chelator cuprizone, and correlated our results with detailed histological analyses, comprising myelination, extracellular matrix alterations, immune cell infiltration and axonal damage. We show firstly that the magnitude of the complex shear modulus decreases with progressive demyelination and global extracellular matrix degradation, secondly that the loss modulus decreases faster than the dynamic modulus during the destruction of the corpus callosum, and finally that those processes are reversible after remyelination.

Prostate MR elastography with transperineal electromagnetic actuation and a fast fractionally encoded steady-state gradient echo sequence.

Our aim is to develop a clinically viable, fast-acquisition, prostate MR elastography (MRE) system with transperineal excitation. We developed a new actively shielded electromagnetic transducer, designed to enable quick deployment and positioning within the scanner. The shielding of the transducer was optimized using simulations. We also employed a new rapid pulse sequence that encodes the three-dimensional displacement field in the prostate gland using a fractionally encoded steady-state gradient echo sequence, thereby shortening the acquisition time to a clinically acceptable 8-10 min. The methods were tested in two phantoms and seven human subjects (six volunteers and one patient with prostate cancer). The MRE acquisition time for 24 slices, with an isotropic resolution of 2 mm and eight phase offsets, was 8 min, and the total scan, including positioning and set-up, was performed in 15-20 min. The phantom study demonstrated that the transducer does not interfere with the acquisition process and that it generates displacement amplitudes that exceed 100 µm even at frequencies as high as 300 Hz. In the in vivo human study, average wave amplitudes of 30 µm (46 µm at the apex) were routinely achieved within the prostate gland at 70 Hz. No pain or discomfort was reported. Results in a single patient suggest that MRE can identify cancer tumors, although this result is preliminary. The proposed methods allow the integration of prostate MRE with other multiparametric MRI methods. The results of this study clearly motivate the clinical evaluation of transperineal MRE in patients.

Assessment of portal hypertension and high-risk oesophageal varices with liver and spleen three-dimensional multifrequency MR elastography in liver cirrhosis.

OBJECTIVE: To assess the value of the liver and spleen viscoelastic parameters at multifrequency MR elastography to determine the degree of portal hypertension and presence of high-risk oesophageal varices in patients with cirrhosis. METHODS: From January to September 2012, 36 consecutive patients with cirrhosis evaluated for transplantation were prospectively included. All patients underwent hepatic venous pressure gradient (HVPG) measurements and endoscopy to assess oesophageal varices. Multifrequency MR elastography was performed within the liver and spleen. The shear, storage and loss moduli were calculated and compared to the HVPG with Spearman coefficients and multiple regressions. Patients with and without severe portal hypertension and high-risk varices were compared with Mann-Whitney tests, logistic regression and ROC analysis. RESULTS: The liver storage and loss moduli and the spleen shear, storage and loss moduli correlated with the HVPG. At multiple regression, only the liver and the spleen loss modulus correlated with the HVPG (r = 0.44, p = 0.017, and r = 0.57, p = 0.002, respectively). The spleen loss modulus was the best parameter for identifying patients with severe portal hypertension (p = 0.019, AUROC = 0.81) or high-risk varices (p = 0.042, AUROC = 0.93). CONCLUSIONS: The spleen loss modulus appears to be the best parameter for identifying patients with severe portal hypertension or high-risk varices. KEY POINTS: 1. Noninvasive HVPG assessment can be performed with liver and spleen MR elastography 2. The spleen loss modulus enables the detection of high-risk oesophageal varices 3. The spleen loss modulus enables the detection of severe portal hypertension.