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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. 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. 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. 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. [Display omitted] [ABSTRACT FROM AUTHOR]

Abstract: Objective: To use an automated water-suppressed magnetic resonance imaging (MRI) method to objectively assess adipose tissue (AT) volumes in whole body and specific regional body components (subcutaneous, thoracic and peritoneal) of obese and lean mice. Materials/Methods: Water-suppressed MR images were obtained on a 7T, horizontal-bore MRI system in whole bodies (excluding head) of 26 week old male C57BL6J mice fed a control (10% kcal fat) or high-fat diet (60% kcal fat) for 20 weeks. Manual (outlined regions) versus automated (Gaussian fitting applied to threshold-weighted images) segmentation procedures were compared for whole body AT and regional AT volumes (i.e., subcutaneous, thoracic, and peritoneal). The AT automated segmentation method was compared to dual-energy X-ray (DXA) analysis. Results: The average AT volumes for whole body and individual compartments correlated well between the manual outlining and the automated methods (R2 >0.77, p<0.05). Subcutaneous, peritoneal, and total body AT volumes were increased 2–3 fold and thoracic AT volume increased more than 5-fold in diet-induced obese mice versus controls (p<0.05). MRI and DXA-based method comparisons were highly correlative (R2 =0.94, p<0.0001). Conclusions: Automated AT segmentation of water-suppressed MRI data using a global Gaussian filtering algorithm resulted in a fairly accurate assessment of total and regional AT volumes in a pre-clinical mouse model of obesity. [Copyright &y& Elsevier]

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/m 2 ; 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., (Copyright © 2024 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

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., (© 2023 The Authors. Journal of Magnetic Resonance Imaging published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)

Objective . The aim of this study is to validate the estimation of the nonlinear shear modulus (A) from the acoustoelasticity theory with two experimental methods, ultrasound (US) elastography and magnetic resonance elastography (MRE), and a finite element method. Approach . Experiments were performed on agar (2%)-gelatin (8%) phantom considered as homogeneous, elastic and isotropic. Two specific setups were built to ensure a uniaxial stress step by step on the phantom, one for US and a nonmagnetic version for MRE. The stress was controlled identically in both imaging techniques, with a water tank placed on the top of the phantom and filled with increasing masses of water during the experiment. In US, the supersonic shear wave elastography was implemented on an ultrafast US device, driving a 6 MHz linear array to measure shear wave speed. In MRE, a gradient-echo sequence was used in which the three spatial directions of a 40 Hz continuous wave displacement generated with an external driver were encoded successively. Numerically, a finite element method was developed to simulate the propagation of the shear wave in a uniaxially stressed soft medium. Main results . Similar shear moduli were estimated at zero stress using experimental methods,μ0US= 12.3 ± 0.3 kPa andμ0MRE= 11.5 ± 0.7 kPa. Numerical simulations were set with a shear modulus of 12 kPa and the resulting nonlinear shear modulus was found to be -58.1 ± 0.7 kPa. A very good agreement between the finite element model and the experimental models (AUS= -58.9 ± 9.9 kPa andAMRE= -52.8 ± 6.5 kPa) was obtained. Significance . These results show the validity of such nonlinear shear modulus measurement quantification in shear wave elastography. This work paves the way to develop nonlinear elastography technique to get a new biomarker for medical diagnosis., (© 2023 Institute of Physics and Engineering in Medicine.)

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., (© 2022 The Authors. Journal of Magnetic Resonance Imaging published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)

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., (© 2022 John Wiley & Sons, Ltd.)

Background & Aims: Tools for the non-invasive diagnosis of non-alcoholic steatohepatitis (NASH) in morbidly obese patients with suspected non-alcoholic fatty liver disease (NAFLD) are an unmet clinical need. We prospectively compared the performance of transient elastography, MRI, and 3 serum scores for the diagnosis of NAFLD, grading of steatosis and detection of NASH in bariatric surgery candidates., Methods: Of 186 patients screened, 152 underwent liver biopsy, which was used as a reference for NAFLD (steatosis [S]>5%), steatosis grading and NASH diagnosis. Biopsies were read by a single expert pathologist. MRI-based proton density fat fraction (MRI-PDFF) was measured in an open-bore, vertical field 1.0T scanner and controlled attenuation parameter (CAP) was measured by transient elastography, using the XL probe. Serum scores (SteatoTest, hepatic steatosis index and fatty liver index) were also calculated., Results: The applicability of MRI was better than that of FibroScan (98% vs. 79%; p <0.0001). CAP had AUROCs of 0.83, 0.79, 0.73 and 0.69 for S>5%, S>33%, S>66% and NASH, respectively. Transient elastography had an AUROC of 0.80 for significant fibrosis (F0-F1 vs. F2-F3). MRI-PDFF had AUROCs of 0.97, 0.95, 0.92 and 0.84 for S>5%, S>33%, S>66% and NASH, respectively. When compared head-to-head in the 97 patients with all valid tests available, MRI-PDFF outperformed CAP for grading steatosis (S>33%, AUROC 0.97 vs. 0.78; p < 0.0003 and S>66%, AUROC 0.93 vs. 0.75; p = 0.0015) and diagnosing NASH (AUROC 0.82 vs. 0.68; p = 0.0056). When compared in "intention to diagnose" analysis, MRI-PDFF outperformed CAP, hepatic steatosis index and fatty liver index for grading steatosis (S>5%, S>33% and S>66%)., Conclusion: MRI-PDFF outperforms CAP for diagnosing NAFLD, grading steatosis and excluding NASH in morbidly obese patients undergoing bariatric surgery., Lay Summary: Non-invasive tests for detecting fatty liver and steatohepatitis, the active form of the disease, have not been well studied in obese patients who are candidates for bariatric surgery. The most popular tests for this purpose are Fibroscan, which can be used to measure the controlled attenuation parameter (CAP), and magnetic resonance imaging, which can be used to measure the proton density fat fraction (MRI-PDFF). We found that, when taking liver biopsy as a reference, MRI-PDFF performed better than CAP for detecting and grading fatty liver as well as excluding steatohepatitis in morbidly obese patients undergoing bariatric surgery., Competing Interests: LC has received lecture’s fees from Abbvie, Echosens, Intercept, Gilead, and Novo Nordisk and consultancy fees from Allergan, Intercept, Gilead, MSD, Novo Nordisk, Pfizer and Servier. No other authors have relevant conflicts of interest. Please refer to the accompanying ICMJE disclosure forms for further details., (© 2021 The Authors.)

Malignant tumors have abnormal biomechanical characteristics, including high viscoelasticity, solid stress, and interstitial fluid pressure. Magnetic resonance (MR) elastography is increasingly used to non-invasively assess tissue viscoelasticity. However, solid stress and interstitial fluid pressure measurements are performed with invasive methods. We studied the feasibility and potential role of MR elastography at basal state and under controlled compression in assessing altered biomechanical features of malignant liver tumors. MR elastography was performed in mice with patient-derived, subcutaneously xenografted hepatocellular carcinomas or cholangiocarcinomas to measure the basal viscoelasticity and the compression stiffening rate, which corresponds to the slope of elasticity versus applied compression. MR elastography measurements were correlated with invasive pressure measurements and digital histological readings. Significant differences in MR elastography parameters, pressure, and histological measurements were observed between tumor models. In multivariate analysis, collagen content and interstitial fluid pressure were determinants of basal viscoelasticity, whereas solid stress, in addition to collagen content, cellularity, and tumor type, was an independent determinant of compression stiffening rate. Compression stiffening rate had high AUC (0.87 ± 0.08) for determining elevated solid stress, whereas basal elasticity had high AUC for tumor collagen content (AUC: 0.86 ± 0.08). Our results suggest that MR elastography compression stiffening rate, in contrast to basal viscoelasticity, is a potential marker of solid stress in malignant liver tumors.

The water proton longitudinal relaxation time, T 1 , is a common and useful MR parameter in nephrology research. Here we provide three step-by-step T 1 -mapping protocols suitable for different types of nephrology research. Firstly, we provide a single-slice 2D saturation recovery protocol suitable for studies of global pathology, where whole-kidney coverage is unnecessary. Secondly, we provide an inversion recovery type imaging protocol that may be optimized for specific kidney disease applications. Finally, we also provide imaging protocol for small animal kidney imaging in a clinical scanner.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 analysis protocol chapter is complemented by two separate chapters describing the basic concept and experimental procedure.

In renal MRI, measurement of the T 1 relaxation time of water molecules may provide a valuable biomarker for a variety of pathological conditions. Due to its sensitivity to the tissue microenvironment, T 1 has gained substantial interest for noninvasive imaging of renal pathology, including inflammation and fibrosis. In this chapter, we will discuss the basic concept of T 1 mapping and different T 1 measurement techniques and we will provide an overview of emerging preclinical applications of T 1 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.

The computation of T 1 maps from MR datasets represents an important step toward the precise characterization of kidney disease models in small animals. Here the main strategies to analyze renal T 1 mapping datasets derived from small rodents are presented. Suggestions are provided with respect to essential software requirements, and advice is provided as to how dataset completeness and quality may be evaluated. The various fitting models applicable to T 1 mapping are presented and discussed. Finally, some methods are proposed for validating the obtained results.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 analysis protocol chapter is complemented by two separate chapters describing the basic concept and experimental procedure.

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 T 1 -weighted, T 2 -weighted, pulsed, and oscillating gradient diffusion-weighted sequences., Assessment: Apparent diffusion coefficient from pulsed (ADC pulsed ) and oscillating gradient (ADC oscillating ) sequences was calculated in 82 nodules identified on the T 1 /T 2 -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 ADC oscillating , increased in the group of nodules with intermediate malignancy (ADC pulsed : 0.75 ± 0.25 × 10 -3 mm 2 /s vs. 0.64 ± 0.07 × 10 -3 mm 2 /s in benign nodules, P = 0.025; ADC oscillating : 0.81 ± 0.20 × 10 -3 mm 2 /s vs. 0.65 ± 0.13 × 10 -3 mm 2 /s, P = 0.0008) and ADC pulsed decreased in the group of progressed hepatocellular carcinomas (ADC pulsed : 0.60 ± 0.08 × 10 -3 mm 2 /s, P = 0.042; ADC oscillating : 0.68 ± 0.08 × 10 -3 mm 2 /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., (© 2019 International Society for Magnetic Resonance in Medicine.)

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., (© 2019 International Society for Magnetic Resonance in Medicine.)

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., (© 2018 International Society for Magnetic Resonance in Medicine.)

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., (Copyright © 2018 John Wiley & Sons, Ltd.)

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. T 2 -weighted, T 1 -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 T 2 signal intensity (4 ± 0.8 versus 2 ± 0.4 AU, P < 0.0001), normalized T 1 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 mm 2 /s, P = 0.0004, and 1.97 × 10 -3 ± 0.43 mm 2 /s versus 1.48 × 10 -3 ± 0.29 mm 2 /s, P = 0.008, respectively). Colorectal wall thickness (r = 0.84, P < 0.0001), normalized T 2 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 T 1 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 T 2 signal intensity, ADC and D, are potential markers of the histopathological inflammation score., (Copyright © 2018 John Wiley & Sons, Ltd.)

Competing Interests: Disclosure The authors report no conflicts of interest in this work.

We have recently reported cannabinoid-induced rapid changes in the structure of individual neurons. In order to investigate the presence of similar effects at the regional level, measures of brain tissue biomechanics are required. However, cannabinoids are known to alter cerebral blood flow (CBF), putatively resulting in presently unexplored changes in cerebral tissue biomechanics. Here we used magnetic resonance elastography (MRE) and flow-sensitive alternating inversion recovery (FAIR) imaging to measure in vivo alterations of mechanical properties and CBF, respectively, in the rat hippocampus, a brain region with a high density of type-1 cannabinoid receptors (CB1R). Systemic injection of the cannabinoid agonist CP55,940 (0.7 mg/kg) induced a significant stiffness decrease of 10.5 ± 1.2% at 15 minutes. FAIR imaging indicated a comparable decrease (11.3 ± 1.9%) in CBF. Both effects were specific to CB1R activation, as shown by pretreatment with the CB1R-specific antagonist AM251. Strikingly, similar rapid parallel changes of brain elasticity and CBF were also observed after systemic treatment with the hypotensive drug nicardipine. Our results reveal important drug-induced parallel changes in CBF and brain mechanical characteristics, and show that blood flow-dependent tissue softening has to be considered as an important putative confounding factor when cerebral viscoelastic changes are investigated., (© The Author(s) 2015.)

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., (© 2015 Wiley Periodicals, Inc.)

Malignant tumors are typically associated with altered rigidity relative to normal host tissue. Magnetic resonance elastography (MRE) enables the noninvasive quantitation of the mechanical properties of deep-seated tissue following application of an external vibrational mechanical stress to that tissue. In this preclinical study, we used MRE to quantify (kPa) the elasticity modulus Gd and viscosity modulus Gl of three intracranially implanted glioma and breast metastatic tumor models. In all these brain tumors, we found a notable softness characterized by lower elasticity and viscosity than normal brain parenchyma, enabling their detection on Gd and Gl parametric maps. The most circumscribed tumor (U-87 MG glioma) was the stiffest, whereas the most infiltrative tumor (MDA-MB-231 metastatic breast carcinoma) was the softest. Tumor cell density and microvessel density correlated significantly and positively with elasticity and viscosity, whereas there was no association with the extent of collagen deposition or myelin fiber entrapment. In conclusion, although malignant tumors tend to exhibit increased rigidity, intracranial tumors presented as remarkably softer than normal brain parenchyma. Our findings reinforce the case for MRE use in diagnosing and staging brain malignancies, based on the association of different tumor phenotypes with different mechanical properties., (©2015 American Association for Cancer Research.)

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., (Copyright © 2014 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Objective: To investigate if magnetic resonance spectroscopy (MRS) is the best Magnetic Resonance (MR)-based method when compared to gradient-echo magnetic resonance imaging (MRI) for the detection and quantification of liver steatosis in diabetic patients in the clinical practice using liver biopsy as the reference standard, and to assess the influence of steatohepatitis and fibrosis on liver fat quantification., Methods: Institutional approval and patient consent were obtained for this prospective study. Seventy-three patients with type 2 diabetes (60 women and 13 men; mean age, 54 ± 9 years) underwent MRI and MRS at 3.0 T. The liver fat fraction was calculated from triple- and multi-echo gradient-echo sequences, and MRS data. Liver specimens were obtained in all patients. The accuracy for liver fat detection was estimated by receiver operator characteristic (ROC) analysis, and the correlation between fat quantification by imaging and histolopathology was analyzed by Spearman's correlation coefficients., Results: The prevalence of hepatic steatosis was 92%. All gradient-echo MRI and MRS findings strongly correlated with biopsy findings (triple-echo, rho = 0.819; multi-echo, rho = 0.773; MRS, rho = 0.767). Areas under the ROC curves to detect mild, moderate, and severe steatosis were: triple-echo sequences, 0.961, 0.975, and 0.962; multi-echo sequences, 0.878, 0.979, and 0.961; and MRS, 0.981, 0.980, and 0.954. The thresholds for mild, moderate, and severe steatosis were: triple-echo sequences, 4.09, 9.34, and 12.34, multi-echo sequences, 7.53, 11.75, and 15.08, and MRS, 1.71, 11.69, and 14.91. Quantification was not significantly influenced by steatohepatitis or fibrosis., Conclusions: Liver fat quantification by MR methods strongly correlates with histopathology. Due to the wide availability and easier post-processing, gradient-echo sequences may represent the best imaging method for the detection and quantification of liver fat fraction in diabetic patients in the clinical practice.

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., (Copyright © 2014 John Wiley & Sons, Ltd.)

Objective: To assess in a high-resolution model of thin liver rat slices which viscoelastic parameter at three-dimensional multifrequency MR elastography has the best diagnostic performance for quantifying liver fibrosis., Materials and Methods: The study was approved by the ethics committee for animal care of our institution. Eight normal rats and 42 rats with carbon tetrachloride induced liver fibrosis were used in the study. The rats were sacrificed, their livers were resected and three-dimensional MR elastography of 5 ± 2 mm liver slices was performed at 7T with mechanical frequencies of 500, 600 and 700 Hz. The complex shear, storage and loss moduli, and the coefficient of the frequency power law were calculated. At histopathology, fibrosis and inflammation were assessed with METAVIR score, fibrosis was further quantified with morphometry. The diagnostic value of the viscoelastic parameters for assessing fibrosis severity was evaluated with simple and multiple linear regressions, receiver operating characteristic analysis and Obuchowski measures., Results: At simple regression, the shear, storage and loss moduli were associated with the severity of fibrosis. At multiple regression, the storage modulus at 600 Hz was the only parameter associated with fibrosis severity (r = 0.86, p<0.0001). This parameter had an Obuchowski measure of 0.89+/-0.03. This measure was significantly larger than that of the loss modulus (0.78+/-0.04, p = 0.028), but not than that of the complex shear modulus (0.88+/-0.03, p = 0.84)., Conclusion: Our high resolution, three-dimensional multifrequency MR elastography study of thin liver slices shows that the storage modulus is the viscoelastic parameter that has the best association with the severity of liver fibrosis. However, its diagnostic performance does not differ significantly from that of the complex shear modulus.