Purpose: To characterize longitudinal changes in molecular water diffusion, blood microcirculation, and their contributions to the apparent diffusion changes using intravoxel incoherent motion (IVIM) analysis in an experimental mouse model of liver fibrosis. Materials and Methods:Liver fibrosis was induced in male adult C57BL/6N mice (22-25 g; n ¼ 12) by repetitive dosing of carbon tetrachloride (CCl 4 ). The respiratorygated diffusion-weighted (DW) images were acquired using single-shot spin-echo EPI (SE-EPI) with 8 b-values and single diffusion gradient direction. True diffusion coefficient (D true ), blood pseudodiffusion coefficient (D pseudo ), and perfusion fraction (P fraction ) were measured. Diffusion tensor imaging (DTI) was also performed for comparison. Histology was performed with hematoxylineosin and Masson's trichrome staining.Results: A significant decrease in D true was found at 2 weeks and 4 weeks following CCl 4 insult, as compared with that before insult. Similarly, D pseudo values before injury was significantly higher than those at 2 weeks and 4 weeks after CCl 4 insult. Meanwhile, P fraction values showed no significant differences over different timepoints. For DTI, significant decrease in ADC was observed following CCl 4 administration. Fractional anisotropy at 2 weeks after CCl 4 insult was significantly lower than that before insult, and subsequently normalized at 4 weeks after the insult. Liver histology showed collagen deposition, the presence of intracellular fat vacuoles, and cell necrosis/apoptosis in livers with CCl 4 insult.Conclusion: Both molecular water diffusion and blood microcirculation contribute to the alteration in apparent diffusion changes in liver fibrosis. Reduction in D true and D pseudo values resulted from diffusion and perfusion changes, respectively, during the progression of liver fibrosis. IVIM analysis may serve as valuable and robust tool in detecting and characterizing liver fibrosis at early stages, monitoring its progression in a noninvasive manner.

Purpose: To characterize changes in relaxation times of liver using quantitative magnetic resonance imaging (MRI) in an experimental mouse model of liver fibrosis. Quantitative MRI is a potentially robust method to characterize liver fibrosis. However, correlation between relaxation times and fibrosis stage has been controversial. Materials and Methods:Liver fibrosis was induced in male adult C57BL/6N mice (22-25 g; n ¼ 12) by repetitive dosing of carbon tetrachloride (CCl 4 ). The animals were examined with a series of spin-echo (SE) images with varying TRs and multiecho SE imaging sequence at 7 T before and 2, 4, 6, and 8 weeks after CCl 4 insult. Hepatic T 1 and T 2 values were measured. Histology was performed with hematoxylin-eosin staining and Masson's trichrome staining.Results: Significant increase (P < 0.001) in hepatic T 1 was found at 2, 4, 6, and 8 weeks following CCl 4 insult as compared with that before insult. Meanwhile, hepatic T 2 at 2, 4, 6, and 8 weeks after CCl 4 insult was significantly higher (P < 0.001) than that before the insult. Liver histology showed collagen deposition, edema, and infiltration of inflammatory cells in livers with CCl 4 insult. Conclusion:Both longitudinal and transverse relaxation times may serve as robust markers for liver fibrosis. With the advent of single breath-hold sequences for MR relaxometry, quantitative mapping of relaxation times can be routinely and reliably performed in abdominal organs and hence may be valuable and robust in detecting liver fibrosis at early phase and monitoring its progression.

Renal ischemia reperfusion injury (IRI) is a major cause of acute renal failure. It occurs in various clinical settings such as renal transplantation, shock and vascular surgery. Serum creatinine level has been used as an index for estimating the degree of renal functional loss in renal IRI. However, it only evaluates the global renal function. In this study, diffusion tensor imaging (DTI) was used to characterize renal IRI in an experimental rat model. Spin-echo echo-planar DTI with b-value of 300 s/mm(2) and 6 diffusion gradient directions was performed at 7 T in 8 Sprague-Dawley (SD) with 60-min unilateral renal IRI and 8 normal SD rats. Apparent diffusion coefficient (ADC), directional diffusivities and fractional anisotropy (FA) were measured at the acute stage of IRI. The IR-injured animals were also examined by diffusion-weighted imaging with 7 b-values up to 1000 s/mm(2) to estimate true diffusion coefficient (D(true)) and perfusion fraction (P(fraction)) using a bi-compartmental model. ADC of injured renal cortex (1.69 +/- 0.24 x 10(-3) mm(2)/s) was significantly lower (p < 0.01) than that of contralateral intact cortex (2.03 +/- 0.35 x 10(-3) mm(2)/s). Meanwhile, both ADC and FA of IR-injured medulla (1.37 +/- 0.27 x 10(-3) mm(2)/s and 0.28 +/- 0.04, respectively) were significantly less (p < 0.01) than those of contralateral intact medulla (2.01 +/- 0.38 x 10(-3) mm(2)/s and 0.36 +/- 0.04, respectively). The bi-compartmental model analysis revealed the decrease in D(true) and P(fraction) in the IR-injured kidneys. Kidney histology showed widespread cell swelling and erythrocyte congestion in both cortex and medulla, and cell necrosis/apoptosis and cast formation in medulla. These experimental findings demonstrated that DTI can probe both structural and functional information of kidneys following renal IRI.

Purpose: To characterize changes in diffusion properties of liver using diffusion tensor imaging (DTI) in an experimental model of liver fibrosis. Materials and Methods:Liver fibrosis was induced in Sprague-Dawley rats (n ¼ 12) by repetitive dosing of carbon tetrachloride (CCl 4 ). The animals were examined with a respiratory-gated single-shot spin-echo echo-planar DTI protocol at 7 T before, 2 weeks after, and 4 weeks after CCl 4 insult. Apparent diffusion coefficient (ADC), directional diffusivities (ADC // and ADC ? ), and fractional anisotropy (FA) were measured. Liver histology was performed with hematoxylin-eosin staining and Masson's trichrome staining.Results: Significant decrease (P < 0.01) in ADC was found at 2 weeks (0.86 6 0.09 Â 10 À3 mm 2 /s) and 4 weeks (0.74 6 0.09 Â 10 À3 mm 2 /s) following CCl 4 insult, as compared with that before insult (0.97 6 0.08 Â 10 À3 mm 2 /s). Meanwhile, FA at 2 weeks (0.18 6 0.03) after CCl 4 insult was significantly lower (P < 0.01) than that before insult (0.26 6 0.05), and subsequently normalized at 4 weeks (0.26 6 0.07) after the insult. Histology showed collagen deposition, presence of intracellular fat vacuoles, and cell necrosis/apoptosis in livers with CCl 4 insult.Conclusion: DTI detected the progressive changes in water diffusivities and diffusion anisotropy of liver tissue in this liver fibrosis model. ADC and FA are potentially valuable in detecting liver fibrosis at early stages and monitoring its progression. Future human studies are warranted to further verify the applicability of DTI in characterizing liver fibrosis and to determine its role in clinical settings.

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