Renal Adiposity Confounds Quantitative Assessment of Markers of Renal Diffusion With MRI: A Proposed Correction Method.

OBJECTIVES: Recent studies have indicated that excessive fat may confound assessment of diffusion in organs with high fat content, such as the liver and breast. However, the extent of this effect in the kidney, which is not considered a major fat deposition site, remains unclear. This study tested the hypothesis that renal fat may impact diffusion-weighted imaging (DWI) parameters, and proposes a 3-compartment model (TCM) to circumvent this effect. METHODS: Using computer simulations, we investigated the effect of fat on assessment of apparent diffusion coefficient (ADC), intravoxel incoherent motion (IVIM), and TCM-derived pure-diffusivity. We also investigated the influence of magnetic resonance repetition (TR) and echo time (TE) on DWI parameters as a result of variation in the relative contribution of the fat signal. Apparent diffusion coefficient, IVIM and TCM DWI parameters were calculated in domestic pigs fed a high-cholesterol (obese group) or normal diet (lean group), and correlated to renal histology. Intravoxel incoherent motion-derived pure-diffusivity was also compared among 15 essential hypertension patients classified by body mass index (BMI) (high vs normal). Finally, pure-diffusivity was calculated and compared in 8 patients with atherosclerotic renal artery stenosis (ARAS) and 5 healthy subjects using IVIM and TCM. RESULTS: Simulations showed that unaccounted fat results in the underestimation of IVIM-derived pure diffusivity. The underestimation increases as the fat fraction increases, with higher pace at lower fat contents. The underestimation was larger for shorter TR and longer TE values due to the enhancement of the relative contribution of the fat signal. Moreover, TCM, which incorporates highly diffusion-weighted images (b > 2500 s/mm), could correct for fat-dependent underestimation. Animal studies in the lean and obese groups confirmed lower ADC and IVIM pure-diffusivity in obese versus lean pigs with otherwise healthy kidneys, whereas pure-diffusivity calculated using TCM were not different between the 2 groups. Similarly, essential hypertension patients with high BMI had lower ADC (1.9 vs 2.1 × 10 mm/s) and pure-diffusivity (1.7 vs 1.9 × 10 mm/s) than those with normal BMI. Pure-diffusivity calculated using IVIM was not different between the ARAS and healthy subjects, but TCM revealed significantly lower diffusivity in ARAS. CONCLUSIONS: Excessive renal fat may cause underestimation of renal ADC and IVIM-derived pure-diffusivity, which may hinder detection of renal pathology. Models accounting for fat contribution may help reduce the variability of diffusivity calculated using DWI.

Assessment of renal artery stenosis using intravoxel incoherent motion diffusion-weighted magnetic resonance imaging analysis.

OBJECTIVES: Diffusion-weighted magnetic resonance imaging is a powerful tool to assess renal morphology. However, its quantitative index, apparent diffusion coefficient (ADC), derived from a conventional monoexponential model can vary with both functional and structural alterations as well as the choice of b values. In contrast, the intravoxel incoherent motion (IVIM) biexponential model provides independent parameters that may represent broader aspects of renal pathophysiology. We hypothesized that IVIM analysis is capable of detecting early morphological and functional changes in the swine kidney distal to renal artery stenosis (RAS). MATERIALS AND METHODS: Domestic pigs divided into 3 groups (n = 6-7 each) were studied for 16 weeks. Unilateral RAS was induced in 2 groups, of which 1 group was fed with a high-cholesterol diet to induce early atherosclerosis (ARAS), whereas the other (RAS) consumed regular diet. The third group included healthy pigs that served as control sham. Renal function, hemodynamics, tubular function, and morphology were assessed using multidetector computed tomography and histology. Diffusion-weighted magnetic resonance images were acquired at 3T and analyzed using monoexponential and biexponential models. Parameters of ADC and IVIM (diffusivity [D(t)], flow-dependent pseudodiffusivity [D(p)], and fluid fraction [f(p)]) were calculated in the cortex and medulla of the stenotic (STK) and contralateral kidneys (CLKs). Results were analyzed using analysis of variance, Student t test, and regression analysis. RESULTS: In both RAS and ARAS, the STK shrank and the CLK underwent hypertrophy. Glomerular filtration rate and renal blood flow declined in STKs, and CLKs manifested hyperfiltration. In addition, ARAS kidneys showed reduced mean transit time in distal tubular segments. Apparent diffusion coefficient and diffusivity both decreased in STK of RAS and ARAS. D(p) and f(p) were elevated in both the STK and CLK of RAS and more prominently in ARAS. The STK cortical ADC and D(t) correlated inversely with the degree of fibrosis and directly with glomerular filtration rate. Furthermore, D(p) correlated with tubular injury score in all kidneys. CONCLUSIONS: Apparent diffusion constant and D(t) both correlated with cortical and medullary fibrosis; however, IVIM-derived parameters can detect subtle functional and structural changes in the post-STK and may also serve as markers for tubular injury.

Noninvasive In vivo assessment of renal tissue elasticity during graded renal ischemia using MR elastography.

OBJECTIVES: : Magnetic resonance elastography (MRE) allows noninvasive assessment of tissue stiffness in vivo. Renal arterial stenosis (RAS), a narrowing of the renal artery, promotes irreversible tissue fibrosis that threatens kidney viability and may elevate tissue stiffness. However, kidney stiffness may also be affected by hemodynamic factors. This study tested the hypothesis that renal blood flow (RBF) is an important determinant of renal stiffness as measured by MRE. MATERIAL AND METHODS: : In 6 anesthetized pigs MRE studies were performed to determine cortical and medullary elasticity during acute graded decreases in RBF (by 20%, 40%, 60%, 80%, and 100% of baseline) achieved by a vascular occluder. Three sham-operated swine served as time control. Additional pigs were studied with MRE 6 weeks after induction of chronic unilateral RAS (n = 6) or control (n = 3). Kidney fibrosis was subsequently evaluated histologically by trichrome staining. RESULTS: : During acute RAS the stenotic cortex stiffness decreased (from 7.4 ± 0.3 to 4.8 ± 0.6 kPa, P = 0.02 vs. baseline) as RBF decreased. Furthermore, in pigs with chronic RAS (80% ± 5.4% stenosis) in which RBF was decreased by 60% ± 14% compared with controls, cortical stiffness was not significantly different from normal (7.4 ± 0.3 vs. 7.6 ± 0.3 kPa, P = 0.3), despite histologic evidence of renal tissue fibrosis. CONCLUSION: : Hemodynamic variables modulate kidney stiffness measured by MRE and may mask the presence of fibrosis. These results suggest that kidney turgor should be considered during interpretation of elasticity assessments.

Quantitative assessment of hepatic fibrosis in an animal model with magnetic resonance elastography.

Chronic liver disease is a world-wide problem that causes progressive hepatic fibrosis as a hallmark of progressive injury. At present, the gold standard for diagnosing hepatic fibrosis is liver biopsy, which is an invasive method with many limitations, including questionable accuracy and risks of complications. MR elastography (MRE), a phase-contrast MRI technique for quantitatively assessing the mechanical properties of soft tissues, is a potential noninvasive diagnostic method to assess hepatic fibrosis. In this work, MRE was evaluated as a quantitative method to assess the in vivo mechanical properties of the liver tissues in a knockout animal model of liver fibrosis. This work demonstrates that the shear stiffness of liver tissue increases systematically with the extent of hepatic fibrosis, as measured by histology. A linear correlation between liver stiffness and fibrosis extent was well-defined in this animal model. An additional finding of the study was that fat infiltration, commonly present in chronic liver disease, does not significantly correlate with liver stiffness at each fibrosis stage and thus does not appear to interfere with the ability of MRE to assess fibrosis extent. In conclusion, MRE has the potential not only for assessing liver stiffness, but also for monitoring potential therapies for hepatic fibrosis.