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.

A Preclinical Validation of Iron Oxide Nanoparticles for Treatment of Perianal Fistulizing Crohn's Disease.

Fistulizing anoperineal lesions are severe complications of Crohn's disease (CD) that affect quality of life with a long-term risk of anal sphincter destruction, incontinence, permanent stoma, and anal cancer. Despite several surgical procedures, they relapse in about two-thirds of patients, mandating innovative treatments. Ultrasmall particles of iron oxide (USPIO) have been described to achieve in vivo rapid healing of deep wounds in the skin and liver of rats thanks to their nanobridging capability that could be adapted to fistula treatment. Our main purpose was to highlight preclinical data with USPIO for the treatment of perianal fistulizing CD. Twenty male Sprague Dawley rats with severe 2,4,6-trinitrobenzenesulfonic acid solution (TNBS)-induced proctitis were operated to generate two perianal fistulas per rat. At day 35, two inflammatory fistulas were obtained per rat and perineal magnetic resonance imaging (MRI) was performed. After a baseline MRI, a fistula tract was randomly drawn and topically treated either with saline or with USPIO for 1 min (n = 17 for each). The rats underwent a perineal MRI on postoperative days (POD) 1, 4, and 7 and were sacrificed for pathological examination. The primary outcome was the filling or closure of the fistula tract, including the external or internal openings. USPIO treatment allowed the closure and/or filling of all the treated fistulas from its application until POD 7 in comparison with the control fistulas (23%). The treatment with USPIO was safe, permanently closed the fistula along its entire length, including internal and external orifices, and paved new avenues for the treatment of perianal fistulizing Crohn's disease.

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.

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.

Gadoxetate-enhanced MR imaging and compartmental modelling to assess hepatocyte bidirectional transport function in rats with advanced liver fibrosis.

OBJECTIVES: Changes in the expression of hepatocyte membrane transporters in advanced fibrosis decrease the hepatic transport function of organic anions. The aim of our study was to assess if these changes can be evaluated with pharmacokinetic analysis of the hepatobiliary transport of the MR contrast agent gadoxetate. METHODS: Dynamic gadoxetate-enhanced MRI was performed in 17 rats with advanced fibrosis and 8 normal rats. After deconvolution, hepatocyte three-compartmental analysis was performed to calculate the hepatocyte influx, biliary efflux and sinusoidal backflux rates. The expression of Oatp1a1, Mrp2 and Mrp3 organic anion membrane transporters was assessed with reverse transcription polymerase chain reaction. RESULTS: In the rats with advanced fibrosis, the influx and efflux rates of gadoxetate decreased and the backflux rate increased significantly (p = 0.003, 0.041 and 0.010, respectively). Significant correlations were found between influx and Oatp1a1 expression (r = 0.78, p < 0.001), biliary efflux and Mrp2 (r = 0.50, p = 0.016) and sinusoidal backflux and Mrp3 (r = 0.61, p = 0.002). CONCLUSION: These results show that changes in the bidirectional organic anion hepatocyte transport function in rats with advanced liver fibrosis can be assessed with compartmental analysis of gadoxetate-enhanced MRI. KEY POINTS: • Expression of hepatocyte transporters is modified in rats with advanced liver fibrosis. • Kinetic parameters at gadoxetate-enhanced MRI are correlated with hepatocyte transporter expression. • Hepatocyte transport function can be assessed with compartmental analysis of gadoxetate-enhanced MRI. • Compartmental analysis of gadoxetate-enhanced MRI might provide biomarkers in advanced liver fibrosis.

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

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

Advanced fibrosis: Correlation between pharmacokinetic parameters at dynamic gadoxetate-enhanced MR imaging and hepatocyte organic anion transporter expression in rat liver.

PURPOSE: To compare the value of enhancement and pharmacokinetic parameters measured at dynamic gadoxetate-enhanced magnetic resonance (MR) imaging in determining hepatic organic anion transporter expression in control rats and rats with advanced liver fibrosis. MATERIALS AND METHODS: Institutional animal review board approval was received before the study began. Advanced liver fibrosis was created in rats by means of carbon tetrachloride injections over an 8-week period. In 17 rats with liver fibrosis and eight control rats, dynamic gadoxetate-enhanced MR images of the liver were obtained during 1 hour after injection of 0.025 mmol gadoxetate per kilogram of body weight. Enhancement parameters (maximum enhancement [Emax], time to peak [Tmax], and elimination half-life) were measured on enhancement-versus-time curves, and pharmacokinetic parameters (hepatic extraction fraction [HEF] and mean residence time [MRT]) were obtained by means of deconvolution analysis of the concentration-versus-time curves in the liver and the portal vein. The parameters were correlated at simple and multiple regression analysis with the expression of the hepatic anion uptake transporter organic anion-transporting polypeptide 1A1 (Oatp1a1), the hepatobiliary transporter multidrug resistance-associated protein 2 (Mrp2), and the backflux transporter Mrp4, as determined with reverse transcription polymerase chain reaction. RESULTS: In rats with advanced liver fibrosis, the Emax, Tmax, HEF, and MRT decreased significantly relative to those in control rats, whereas the elimination half-life increased significantly. The enhancement and pharmacokinetic parameters correlated significantly with the expression of the transporters at simple regression analysis. At multiple regression analysis, HEF was the only parameter that was significantly associated with the expression of Oatp1a1 and Mrp2 (P < .001, r = 0.74 and P < .001, r = 0.70, respectively). CONCLUSION: The pharmacokinetic parameter HEF at dynamic gadoxetate-enhanced MR imaging is independently correlated with hepatic organic anion transporter expression.

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.

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.

Fat deposition decreases diffusion parameters at MRI: a study in phantoms and patients with liver steatosis.

PURPOSE: Assess the effect of fat deposition on the MRI diffusion coefficients in lipid emulsion-based phantoms and patients with proven isolated liver steatosis. MATERIALS AND METHODS: Diffusion-weighted MRI with 11 b values from 0-500 s/mm(2) was performed in phantoms (fat fractions 0-18 %) with and without fat suppression and in 19 patients with normal liver (n = 14) or isolated liver steatosis (n = 5) proven by histopathology. The apparent, pure and perfusion-related diffusion coefficients and the perfusion fraction were measured. Spearman correlation coefficient and Mann-Whitney U test were used for comparisons. RESULTS: A strong correlation between the apparent and pure diffusion coefficients and fat fractions was seen in phantoms. The pure diffusion coefficient decreased significantly in patients with liver steatosis (0.96 ± 0.16 × 10(-3) mm(2)/s versus 1.18 ± 0.09 × 10(-3) mm(2)/s in normal liver, P = 0.005), whereas the decrease in apparent diffusion coefficient did not reach statistical significance (1.26 ± 0.25 × 10(-3) mm(2)/s versus 1.41 ± 0.14 × 10(-3) mm(2)/s in normal liver, P = 0.298). CONCLUSIONS: Fat deposition decreases the apparent and pure diffusion coefficients in lipid emulsion-based phantoms and patients with isolated liver steatosis proven by histopathology.

Diffusion-weighted MR imaging for the regional characterization of liver tumors.

PURPOSE: To determine if diffusion-weighted (DW) magnetic resonance (MR) imaging with measurements of the apparent diffusion coefficient (ADC), pure diffusion coefficient, perfusion-related diffusion coefficient, and perfusion fraction can be used to differentiate between viable tumor and fibrous and necrotic regions within malignant liver tumors. MATERIAL AND METHODS: The prospective study was approved by the institutional review board, and informed consent was obtained from all patients. Forty-eight patients with 51 malignant tumors were assessed. MR images of the liver were obtained by using DW imaging with 11 b factors (0-500 sec/mm(2)) and gadolinium-enhanced three-dimensional gradient-echo T1-weighted imaging. Tumors were segmented into viable tumor and fibrous and necrotic regions according to the enhancement pattern after injection of a nonspecific gadolinium chelate and, in surgically removed lesions, results of histopathologic correlation. The ADC, pure diffusion coefficient, perfusion-related diffusion coefficient, and perfusion fraction were calculated, and values were compared between viable tumor and fibrous and necrotic regions with the Kruskal-Wallis test followed by the Dunn multiple comparison test. RESULTS: The pure diffusion coefficient differed significantly between regions of viable tumor tissue and fibrosis (1.16 × 10(-3) mm(2)/sec ± 0.29 and 1.48 × 10(-3) mm(2)/sec ± 0.31, respectively; P = .016) and between regions of viable tumor tissue and necrosis (1.70 × 10(-3) mm(2)/sec ± 0.49, P = .002). There was a significantly lower perfusion fraction in necrotic regions (14% ± 6) than in viable tumor regions (21% ± 8, P = .005), but the perfusion fraction of the fibrous regions (21% ± 7) did not differ significantly from that of the other two regions. ADCs and perfusion-related diffusion coefficients did not differ significantly among the three regions. CONCLUSION: Results of this study show that viable tumor regions in malignant liver tumors can be differentiated from fibrous and necrotic regions with use of the pure diffusion coefficient but not with the other diffusion parameters.

In vivo characterization of several rodent glioma models by 1H MRS.

The assessment of metabolites by (1)H MRS can provide information regarding glioma growth, and may be able to distinguish between different glioma models. Rat C6, 9 L/LacZ, F98 and RG2, and mouse GL261, cells were intracerebrally implanted into the respective rodents, and human U87 MG cells were implanted into athymic rats. Ethyl-nitrosourea induction was also used. Glioma metabolites [e.g. total choline (tCho), total creatine (tCr), N-acetylaspartate (NAA), lactate (Lac), glutamine (Gln), glutamate (Glu), aspartate (Asp), guanosine (Gua), mobile lipids and macromolecules (MMs)] were assessed from (1)H MRS using point-resolved spectroscopy (PRESS) [TE = 24 ms; TR = 2500 ms; variable pulse power and optimized relaxation delay (VAPOR) water suppression; 27-µL and 8-µL voxels in rats and mice, respectively] at 7 T. Alterations in metabolites (Totally Automatic Robust Quantitation in NMR, TARQUIN) in tumors were characterized by increases in lipids (Lip1.3: 8.8-54.5 mM for C6 and GL261) and decreases in NAA (1.3-2.0 mM for RG2, GL261 and C6) and tCr (0.8-4.0 mM for F98, RG2, GL261 and C6) in some models. F98, RG2, GL261 and C6 models all showed significantly decreased (p < 0.05) tCr, and RG2, GL261 and C6 models all exhibited significantly decreased (p < 0.05) NAA. The RG2 model showed significantly decreased (p < 0.05) Gln and Glu, the C6 model significantly decreased (p < 0.05) Asp, and the F98 and U87 models significantly decreased (p < 0.05) Gua, compared with controls. The GL261 model showed the greatest alterations in metabolites. (1)H MRS was able to differentiate the metabolic profiles in many of the seven rodent glioma models assessed. These models are considered to resemble certain characteristics of human glioblastomas, and this study may be helpful in selecting appropriate models.

MR elastography of liver tumours: value of viscoelastic properties for tumour characterisation.

OBJECTIVES: To assess the value of the viscoelastic parameters in the characterisation of liver tumours at MR elastography. PATIENTS AND METHODS: Ninety-four patients with liver tumours >1 cm prospectively underwent MR elastography using 50-Hz mechanical waves and a full three-directional motion-sensitive sequence. The model-free viscoelastic parameters (the complex shear modulus and its real and imaginary parts, i.e. the storage and loss moduli) were calculated in 72 lesions after exclusion of cystic, treated or histopathologically undetermined tumours. RESULTS: We observed higher absolute shear modulus and loss modulus in malignant versus benign tumours (3.38 ± 0.26 versus 2.41 ± 0.15 kPa, P < 0.01 and 2.25 ± 0.26 versus 1.05 ± 0.13 kPa, P < 0.001, respectively). Moreover, the loss modulus of hepatocellular carcinomas was significantly higher than in benign hepatocellular tumours. The storage modulus did not differ significantly between malignant and benign tumours. The area under the receiver-operating characteristic curve of loss modulus was significantly larger than that of the absolute shear modulus and storage modulus when comparing malignant and benign lesions. CONCLUSIONS: The increased loss modulus is a better discriminator between benign and malignant tumours than the increased storage modulus or absolute value of the shear modulus. KEY POINTS : • Magnetic Resonance elastography is a new method of assessing the liver. • Increased loss modulus is an indicator of malignancy in hepatic tumours. • Loss modulus is a better discriminator than absolute shear modulus values. • The viscoelastic properties of lesions offer promise for characterising liver tumours.

New acquisition techniques: fields of application.

Conventional MR imaging of the liver has a central role in the assessment of liver diseases. Diffusion-weighted MR imaging, MR elastography, and time-resolved dynamic contrast-enhanced MR imaging improve the anatomical information provided by conventional MR imaging and add quantitative functional information in diffuse and focal liver diseases. Particularly, accurate detection and characterization of liver fibrosis are feasible with quantitative MR elastography, detection of liver tumors is increased with diffusion-weighted MR imaging and time-resolved dynamic contrast-enhanced MR imaging, characterization of tumors can be improved with quantitative diffusion-weighted MR imaging and MR elastography. These methods also have the potential to provide adequate biomarkers for assessing the response to treatment. Currently, the main limitations of quantitative MR imaging are related to reproducibility, standardization, and/or limited clinical data. It is important to improve and standardize the quantitative MR methods and validate their role in large multicenter trials.

Molecular MRI assessment of vascular endothelial growth factor receptor-2 in rat C6 gliomas.

Angiogenesis is essential to tumour progression and a precise evaluation of angiogenesis is important for tumour early diagnosis and treatment. The quantitative and dynamic in vivo assessment of tumour angiogenesis can be achieved by molecular magnetic resonance imaging (mMRI). Vascular endothelial growth factor (VEGF) and VEGF receptors (VEGFRs) are the main regulatory systems in angiogenesis and have been used as hot targets for radionuclide-based molecular imaging. However, little research has been accomplished in targeting VEGF/VEGFRs by mMRI. In our study, we aimed to assess the expression of VEGFR2 in C6 gliomas by using a specific molecular probe with mMRI. The differential uptake of the probe conjugated to anti-VEGFR2 monoclonal antibody, shown by varied increases in T(1) signal intensity during a 2 hr period, demonstrated the heterogeneous expression of VEGFR2 in different tumour regions. Microscopic fluorescence imaging, obtained for the biotin group in the probe with streptavidin-Cy3, along with staining for cellular VEGFR2 levels, laminin and CD45, confirmed the differential distribution of the probe which targeted VEGFR2 on endothelial cells. The angiogenesis process was also assessed using magnetic resonance angiography, which quantified tumour blood volume and provided a macroscopic view and a dynamic change of the correlation between tumour vasculature and VEGFR2 expression. Together these results suggest mMRI can be very useful in assessing and characterizing the expression of specific angiogenic markers in vivo and help evaluate angiogenesis associated with tumour progression.

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.

Experimental Protocols for MRI Mapping of Renal T1.

The water proton longitudinal relaxation time, T1, is a common and useful MR parameter in nephrology research. Here we provide three step-by-step T1-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.