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Assessment of Abnormal Renal Function using Diffusion Weighted Imaging: 

Diffusion-weighted (DW) MRI is an imaging technique used to measure the microscopic thermally-induced random motion of water molecules referred to as self-diffusion or Brownian motion (16). The rate of water diffusion is described by the apparent diffusion coefficient (ADC) and combines the effects of water transport and its diffusion in and around cells. Thus, it can potentially be used to improve differentiation of normal and abnormal structures of tissues and the characterization of various abnormalities. Since the transport of water within the kidney is exceptionally complex, depending on glomerular filtration, active and passive tubular reabsorption, and secretion, DW-MRI may prove useful for characterizing different mouse models of renal disease. In small animals models DWI has shown potential in monitoring early graft rejection following kidney transplant (17), decreased medullary ADC in acute ureteral obstruction and decreased cortical ADC in chronic ureteral obstruction (18). Lower than normal ADC values have also been found in rats with induced acute renal failure and diabetic kidneys (19, 20).

(Preliminary DWI Studies)
In our preliminary DWI studies we acquired spin-echo diffusion weighted images of control mouse kidneys at 6 b-values (0,50,100,500,750,1000). Diffusion weighting was equally applied in three orthogonal directions. Respiratory gating was used to minimize motion artifacts. An example ADC map computed from all b-values is illustrated in Figure 6. The average cortical and medulla ADC values were 1.58 and 1.94, respectively. We also compared ADC maps computed using only the low b-values (50,100) to those using high b-values (500-1000) and found that the mean ADC for low b-values (ADClow) was substantially higher than that computed using high b-values (ADChigh). This supports the notion that ADClow has increased sensitivity to water transport inside the kidney (e.g. perfusion).

(Developmental DWI Studies)
Although diffusion weighted imaging has shown potential to assess renal abnormalities, its utility in mice needs further investigation and optimization. In addition to standard DWI methods we are also pioneering the use of oscillating gradient spin echo (OGSE) measurements to measure ADC at a finer scale. Briefly, while conventional measurements of ADC reflect diffusion restrictions due to cell membranes and water transport OGSE measurements of diffusion provide image contrast that is sensitive to variations of intracellular structures. We are applying OGSE methods to study kidney disease models to evaluate whether this technique can provide new information on disease progression or response to treatment. The following studies will be performed to further validate the use of this technique in mice to assess kidney pathology. Given the success of earlier studies we will collect standard and OGSE DWI measurements in a kidney transplant model and in an ischemia/reperfusion model. The derived ADC measurements will be compared with measures of renal blood flow, as determined by PAH clearance (see pathophysiology and physiology core for detailed method), glomerular filtration rate (GFR) as determined from FITC-inulin clearance and pathology.

Publications for DW-MRI (Tissue injury) (5)

Thoeny HC, Zumstein D, Simon-Zoula S, Eisenberger U, De Keyzer F, Hofmann L, Vock P, Boesch C, Frey FJ, Vermathen P. Functional evaluation of transplanted kidneys with diffusion-weighted and BOLD MR imaging: initial experience. Radiology (2006) 241:812-21
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PURPOSE: To prospectively evaluate feasibility and reproducibility of diffusion-weighted (DW) and blood oxygenation level-dependent (BOLD) magnetic resonance (MR) imaging in patients with renal allografts, as compared with these features in healthy volunteers with native kidneys. MATERIALS AND METHODS: The local ethics committee approved the study protocol; patients provided written informed consent. Fifteen patients with a renal allograft and in stable condition (nine men, six women; age range, 20-67 years) and 15 ageand sex-matched healthy volunteers underwent DW and BOLD MR imaging. Seven patients with renal allografts were examined twice to assess reproducibility of results. DW MR imaging yielded a total apparent diffusion coefficient including diffusion and microperfusion (ADC(tot)), as well as an ADC reflecting predominantly pure diffusion (ADC(D)) and the perfusion fraction. R2* of BOLD MR imaging enabled the estimation of renal oxygenation. Statistical analysis was performed, and analysis of variance was used for repeated measurements. Coefficients of variation between and within subjects were calculated to assess reproducibility. RESULTS: In patients, ADC(tot), ADC(D), and perfusion fraction were similar in the cortex and medulla. In volunteers, values in the medulla were similar to those in the cortex and medulla of patients; however, values in the cortex were higher than those in the medulla (P < .05). Medullary R2* was higher than cortical R2* in patients (12.9 sec(-1) +/2.1 [standard deviation] vs 11.0 sec(-1) +/0.6, P < .007) and volunteers (15.3 sec(-1) +/1.1 vs 11.5 sec(-1) +/0.5, P < .0001). However, medullary R2* was lower in patients than in volunteers (P < .004). Increased medullary R2* was paralleled by decreased diffusion in patients with allografts. A low coefficient of variation in the cortex and medulla within subjects was obtained for ADC(tot), ADC(D), and R2* (<5.2%), while coefficient of variation within subjects was higher for perfusion fraction (medulla, 15.1%; cortex, 8.6%). Diffusion and perfusion indexes correlated significantly with serum creatinine concentrations. CONCLUSION: DW and BOLD MR imaging are feasible and reproducible in patients with renal allografts. CI (c) RSNA, 2006.

Pedersen M, Wen JG, Shi Y, Beigi N, Christensen TB, Stodkilde-Jorgensen H, Frokiaer J. The effect of unilateral ureteral obstruction on renal function in pigs measured by diffusion-weighted MRI. APMIS Suppl (2003) null:29-34
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The objective of this study was to examine the effect of unilateral ureteral obstruction on the apparent diffusion coefficient (ADC) in pig kidney. Changes in ADC is suggested to reflect changes in the ratio of extracellular to intracellular volume. Thirteen pigs were allocated into three groups: 1) pigs subjected to acute unilateral ureteral obstruction (AUO) (n = 3), 2) pigs subjected to chronic partial unilateral obstruction (CPUO) (n = 3), and 3) control pigs (n = 7). The extrato intracellular volume ratio was indirectly measured in both the ipsilateral obstructed kidney and contralateral non-obstructed kidney by the ADC of the renal tissue using diffusion-weighted echo-planar magnetic resonance imaging. ADC was 2.07 +/0.27 x 10(-3) mm2/s in the cortex and 2.10 +/0.24 x 10(-3) mm2/s in the medulla of normal control kidneys. In the obstructed kidney from the AUO group the ADC of the medulla was significantly reduced 24 hours after occlusion of the ureter (1.65 +/0.05 x 10(-3) mm2/s vs 2.10 +/0.24 x 10(-3) mm2/s; p < 0.05). Similarly ADC decreased slightly in the cortex of the ipsilateral kidney. In contrast, ADC of the ipsilateral kidney of CPUO pigs was increased both in the renal medulla (3.13 +/- 0.21 x 10(-3) mm2/s vs. 2.10 +/0.24 x 10(-3) mm2/s; p < 0.05) and cortex (3.09 +/0.14 x 10(-3) mm2/s vs. 2.07 x 10(-3) mm2/s, p < 0.05). In conclusion, the results of the present study suggest that diffusion weighted imaging (ADC) may be a useful parameter to incorporate when identifying whether a ureteric obstruction is acute or chronic.

Ries M, Basseau F, Tyndal B, Jones R, Deminiere C, Catargi B, Combe C, Moonen CW, Grenier N. Renal diffusion and BOLD MRI in experimental diabetic nephropathy. Blood oxygen level-dependent. J Magn Reson Imaging (2003) 17:104-13
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PURPOSE: To investigate the possibility of using combined blood oxygen level-dependent (BOLD) imaging and diffusion-weighted imaging (DWI) to detect pathological and physiological changes in renal tissue damage of the kidney induced by chronic renal hyperfiltration. MATERIALS AND METHODS: The apparent diffusion coefficient (ADC) and the T(2)* value within the inner compartments of the kidneys of 17 rats with diabetes mellitus were compared with the results obtained from a control group (N = 16). The influence of dynamic changes of the renal function on the blood-oxygen saturation was evaluated by comparing the T(2)* values before and after the active reduction of tubular transport by furosemide injection. RESULTS: All compartments of the diabetic kidney showed significantly (P < 0.05) lower T(2)*-values compared to the control group. In particular, the very low values in the outer stripe (OS) of the outer medulla (OM) (T(2)*-normal: 69.4 +/10.9 msec; T(2)*-diabetic: 51.4 +/13.9 msec) indicated either hypoxia due to hyperfiltration, or renal blood volume changes. Diffusion imaging of the same area showed significantly lower ADC values (ADC-normal: 1.45 +/0.26; ADC-edema: 1.19 +/0.25 [10(-9)m(2)/s]) that correlated with pathological findings on histopathology. The injection of furosemide significantly (P < 0.05) increased T(2)* in all compartments of both populations while the ADC remained unchanged. CONCLUSION: BOLD-contrast imaging appears to be able to depict tissue at risk from ischemia by revealing information about the balance between tubular workload and delivery of oxygen, and thus may reflect a measure of the reserve capacity. The diffusion measurements apparently reveal complementary information. Although ADC imaging is not sensitive to the current energy metabolism, it appears toreflect the pathological changes within the issue. Therefore, ADC measurements may be a sensitive indicator of the severity of ischemic lesions. CI Copyright 2002 Wiley-Liss, Inc.

Vexler VS, Roberts TP, Rosenau W. Early detection of acute tubular injury with diffusion-weighted magnetic resonance imaging in a rat model of myohemoglobinuric acute renal failure. Ren Fail (1996) 18:41-57
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We evaluated the feasibility of magnetic resonance imaging (MRI) for early detection of tubular injury by monitoring changes in the apparent diffusion coefficient (ADC) of renal water in a rat model of myohemoglobinuric glycerol-induced acute renal failure (ARF). Diffusion-weighted MRI was performed concurrently with measurements of serum creatinine and blood urea nitrogen (BUN), evaluation of renal perfusion with dynamic contrast-enhanced MRI, and renal morphological examination. ADC values in the cortex and outer medulla significantly declined within minutes after the glycerol administration (70-75% of control at 4 min and 50-60% of control at 15 min). Contrast-enhanced MRI demonstrated renal hypoperfusion at 20 min after the onset of injury. Light microscopy showed normal glomeruli and edematous tubular epithelial cells at 10 and 30 min, with more severe swelling and protein casts at 30 min. No changes in serum creatinine or BUN levels were detected. We hypothesize that decrease in renal ADC may be attributed to renal ischemia and to subsequent intracellular accumulation of diffusion-restricted water. Similar imaging evaluation in other experimental models of ARF, and in patients, will define the diagnostic value of renal ADC changes in early detection of acute tubular injury.

Le Bihan D, Breton E, Lallemand D, Aubin ML, Vignaud J, Laval-Jeantet M. Separation of diffusion and perfusion in intravoxel incoherent motion MR imaging. Radiology (1988) 168:497-505
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Intravoxel incoherent motion (IVIM) imaging is a method the authors developed to visualize microscopic motions of water. In biologic tissues, these motions include molecular diffusion and microcirculation of blood in the capillary network. IVIM images are quantified by an apparent diffusion coefficient (ADC), which integrates the effects of both diffusion and perfusion. The aim of this work was to demonstrate how much perfusion contributes to the ADC and to present a method for obtaining separate images of diffusion and perfusion. Images were obtained at 0.5 T with high-resolution multisection sequences and without the use of contrast material. Results in a phantom made of resin microspheres demonstrated the ability of the method to separately evaluate diffusion and perfusion. The method was then applied in patients with brain and bone tumors and brain ischemia. Clinical results showed significant promise of the method for tissue characterization by perfusion patterns and for functional studies in the evaluation of the microcirculation in physiologic and pathologic conditions, as, for instance, in brain ischemia.

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Last updated on 2013-11-06 Moderated by Takamune Takahashi