Marcel Gutberlet

Magnetic resonance diffusion tensor imaging for evaluation of histopathological changes in a rat model of diabetic nephropathy.

ObjectivesThe aim of this study was to investigate whether magnetic resonance (MR) diffusion tensor imaging (DTI) allows assessment of renal pathologies in a rat model of diabetic nephropathy. Materials and MethodsTwenty-one male Sprague-Dawley rats were divided into 3 groups: (1) untreated controls, (2) diabetes (DM), (3) diabetes with uninephrectomy (DM UNX) to accelerate renal impairment. Eight weeks after diabetes induction with streptozotocin, MR imaging was performed in a 1.5-T scanner using an 8-channel wrist coil. Morphological proton density images and echoplanar DTI were obtained (b = 0 and 300 s/mm2, 6 diffusion directions). Renal apparent diffusion coefficient (ADC) and fractional anisotropy (FA) values were calculated for each of the different anatomical layers of the kidney. Imaging results, laboratory parameters of diabetic state and kidney function, and renal histopathological changes (glomerulosclerosis, tubular dilatation, and renal fibrosis) were compared between groups. Correlations between FA and histopathological changes were evaluated. ResultsAll diabetic animals developed hyperglycemia and hypoinsulinemia. Uremia, albuminuria, and histopathological changes were most pronounced in DM UNX animals. Fractional anisotropy was significantly reduced in DM UNX animals in the cortex (CO) (0.167; confidence interval [CI], 0.151–0.184; P < 0.001), outer stripe of the outer medulla (OS) (0.254; CI, 0.225–0.283; P = 0.038), and inner medulla (IM) (0.459; CI, 0.395–0.523; P = 0.008) compared with control animals (CO, 0.251; CI, 0.224–0.277; OS, 0.309; CI, 0.267–0.350; IM, 0.559; CI, 0.515–0.603). In DM-without-UNX animals, only cortical FA was significantly lower than in controls (P < 0.001). Between groups, ADC values were not different, except for cortical ADC, which was higher in DM UNX animals than in controls. Significant negative correlations were observed between the FA of different anatomical layers and the extent of glomerulosclerosis (CO, P = 0.003, r = −0.65; and OS, P = 0.022, r = −0.52), tubulointerstitial fibrosis (IM, P = 0.028, r = −0.50), and tubular dilatation (CO, P = 0.015, r = −0.55; and IM, P = 0.006, r = −0.61), respectively. ConclusionsMagnetic resonance DTI by reduction of FA identified renal pathologies of diabetic nephropathy such as glomerulosclerosis, interstitial fibrosis, and tubular damage. Representing different stages of disease, DM and DM UNX animals could be differentiated. Thus, MR DTI may be valuable for noninvasive detection and monitoring of renal pathology in patients with diabetes.

T2 relaxation time and apparent diffusion coefficient for noninvasive assessment of renal pathology after acute kidney injury in mice: comparison with histopathology.

IntroductionRenal ischemia reperfusion injury leads to acute kidney injury (AKI) and is associated with tissue edema, inflammatory cell infiltration, and subsequent development of interstitial renal fibrosis and tubular atrophy. The purpose of this study was to investigate the value of the functional magnetic resonance imaging (MRI) techniques, T2 mapping, and diffusion-weighted imaging (DWI) in characterizing acute and chronic pathology after unilateral AKI in mice. Materials and MethodsModerate or severe AKIs were induced in C57Bl/6 mice through transient unilateral clamping of the renal pedicle for 35 minutes (moderate AKI) or 45 minutes (severe AKI), respectively. Magnetic resonance imaging was performed in 10 animals with moderate AKI and 7 animals with severe AKI before surgery and at 5 time points thereafter (days 1, 7, 14, 21, 28) using a 7-T magnet. Fat-saturated T2-weighted images, multiecho turbo spin echo, and diffusion-weighed sequences (7 b values) were acquired in matching coronal planes. Parameter maps of T2 relaxation time and apparent diffusion coefficient (ADC) were calculated, and mean values were determined for the renal cortex, the outer medulla, and the inner medulla. Inflammatory cell infiltration with monocytes/macrophages (F4/80), T-lymphocytes (CD4, CD8), and dendritic cells (CD11c) as well as the degree of interstitial fibrosis 4 weeks after AKI were determined through renal histology and immunohistochemistry. Statistical analysis comprised unpaired t tests for group comparisons and correlation analysis between MRI parameters and kidney volume loss. ResultsIncrease of T2 relaxation time, indicating tissue edema, was most pronounced in the outer medulla and reached maximum values at d7 after AKI. At this time point, T2 values in the outer medulla were significantly increased to 53.8 ± 2.5 milliseconds after the severe AKI and to 46.3 ± 2.3 milliseconds after the moderate AKI when compared with the respective contralateral normal kidneys (40.9 ± 0.9 and 36.4 ± 1.2 milliseconds, respectively; P < 0.01). The T2 values reached baseline by d28. Medullary ADC was significantly reduced at all time points after AKI; restriction of diffusion was significantly more pronounced after the severe AKI than after the moderate AKI at d14 and d28. Changes of renal T2 and ADC values were associated with the severity of AKI as well as the degree of inflammatory cell infiltration and interstitial renal fibrosis 4 weeks after AKI. Furthermore, relative changes of both MRI parameters significantly correlated with kidney volume loss 4 weeks after AKI. DiscussionMeasuring T2 and ADC values through MRI is a noninvasive way to determine the presence and severity of acute and chronic renal changes after AKI in mice. Thus, the method should prove useful in animal and human clinical studies.

Acute Kidney Injury: Arterial Spin Labeling to Monitor Renal Perfusion Impairment in Mice—Comparison with Histopathologic Results and Renal Function

PURPOSE To determine if arterial spin-labeling (ASL) magnetic resonance (MR) imaging can show serial changes in renal perfusion in mice with ischemia-induced acute kidney injury (AKI) and to compare imaging results with those of renal histologic examination and inulin and para-aminohippuric acid (PAH) clearance. MATERIALS AND METHODS In this animal care committee-approved study, AKI was induced in C57Bl/6 mice (n = 26) by clamping the right renal pedicle for 35 minutes for moderate (n = 16) or 45 minutes (n = 11) for severe AKI. Renal perfusion was measured in 10 animals with moderate and seven animals with severe AKI before and at five time points 1-28 days after surgery by using ASL with a 7-T MR imaging unit. Kidney volume loss and histologic evidence of acute tubular injury were assessed. Inulin and PAH clearance was determined in four animals with moderate and six animals with severe AKI to evaluate renal function and plasma flow for statistical analysis. Repeated measures analysis of variance, unpaired t tests, and correlation analysis were used. RESULTS Renal perfusion values at day 7 were significantly reduced after moderate (56% ± 8; P < .01) and severe (33% ± 6; P < .001) AKI compared with presurgery values. Renal perfusion had returned to baseline levels at day 21 after moderate (96% ± 14) and remained compromised until day 28 after severe (46 % ± 9; P < .05) AKI. At day 28, for moderate versus severe AKI, kidney volume (84% ± 6 vs 60% ± 5; P < .05), degree of tubular injury (5.6% ± 1.8 vs 15.8% ± 2.4; P < .01), and inulin and para-aminohippuric acid clearance (47.5 µL/min ± 5.6 vs 7.3 µL/min ± 2.7; P < .001 and 100.8 µL/min ± 24.3 vs 4.8 µL/min ± 1.0; P < .001, respectively) were significantly different. Relative renal perfusion at days 7-28 significantly correlated with kidney volume loss (P < .01) and tubular injury (P < .05) 4 weeks after AKI. CONCLUSION ASL allows evaluation of renal perfusion impairment associated with kidney volume loss and histologic changes after AKI in mice and may serve as a noninvasive biomarker for AKI.

Virtual Coil Concept for Improved Parallel MRI Employing Conjugate Symmetric Signals

A new approach for utilizing conjugate k‐space symmetry for improved parallel MRI performance is presented. By generating virtual coils containing conjugate symmetric k‐space signals from actual coils, additional image‐ and coil‐phase information can be incorporated into the reconstruction process for parallel acquisition techniques. In that way the reconstruction conditions are improved, resulting in less noise enhancement. In particular in combination with generalized autocalibrating partially parallel acquisitions (GRAPPA), the virtual coil concept represents a practical approach since no explicit spatial phase information is required. In addition, the influence of phase variations originating from the complex receiver coils as well as from the background is investigated. It is shown that there exist background phase distributions yielding an optimized pMRI reconstruction. Magn Reson Med 61:93–102, 2009.

Diffusion-Weighted imaging and diffusion tensor imaging detect delayed graft function and correlate with allograft fibrosis in patients early after kidney transplantation.

To combine diffusion‐weighted imaging (DWI) and diffusion tensor imaging (DTI) for detection of allograft dysfunction in patients early after kidney transplantation and to correlate diffusion parameters with renal function and renal histology of allograft biopsies.

Performance of perfusion-weighted Fourier decomposition MRI for detection of chronic pulmonary emboli

To evaluate the test performance of perfusion‐weighted Fourier‐decomposition (pw‐FD) magnetic resonance imaging (MRI) in comparison to dynamic contrast‐enhanced (DCE)‐MRI as a reference standard in patients with known or suspected chronic pulmonary embolism (PE).

Kidney Transplantation: Multiparametric Functional Magnetic Resonance Imaging for Assessment of Renal Allograft Pathophysiology in Mice.

ObjectivesThe aims of this experimental study were to investigate renal allograft pathophysiology by multiparametric functional magnetic resonance imaging (MRI) and to directly correlate MRI parameters with renal histopathology in mouse models of allogenic and isogenic kidney transplantation (ktx). Materials and MethodsAllograft rejection was induced by transplantation of C57BL/6 (B6) donor kidneys into BALB/c recipients (allogenic ktx). B6 mice that received B6 kidneys served as controls (isogenic ktx). Three weeks after ktx, MRI was performed using a 7-T small-animal scanner. Flow sensitive alternating inversion recovery echoplanar imaging arterial spin labeling, multiecho turbo spin echo, and diffusion-weighted imaging sequences were acquired. Maps of renal perfusion, T2 and T1 relaxation times, and apparent diffusion coefficients were calculated. Histological changes in the kidney were evaluated according to Banff criteria. Renal cell infiltrates and fibrosis were quantified by immunohistochemistry. Differences between groups were assessed using the Mann-Whitney U test, and the correlation of MRI parameters with renal histopathology was determined by Spearman correlation analysis. ResultsAfter allogenic, but not isogenic, ktx, animals developed acute allograft rejection. Allogenic grafts were infiltrated by macrophages and T-lymphocytes and exhibited marked renal fibrosis. Magnetic resonance imaging revealed stronger impairment of renal perfusion (56 ± 7 vs 293 ± 44 mL/[min × 100 g]; P < 0.01) and more pronounced increases in T2 (60.1 ± 2.0 vs 45.7 ± 1.2 milliseconds, P < 0.01) and T1 relaxation times (1938 ± 53 vs 1350 ± 27 milliseconds, P < 0.01) in allogenic than in isogenic kidneys. Apparent diffusion coefficient was reduced to 1.39 ± 0.14 × 10−3 mm2/s in kidneys with an acute rejection and was 1.83 ± 0.05 × 10−3 mm2/s in isogenic kidneys without rejection (P < 0.05). Magnetic resonance imaging parameters significantly correlated with the amount of cellular infiltration and renal fibrosis observed histologically. ConclusionsFunctional MRI allows detection of acute renal allograft rejection after allogenic ktx in mice. Functional MRI parameters correlate with cell infiltrates and fibrosis. Thus, MRI may be used noninvasively and longitudinally to investigate mechanisms of renal allograft rejection and evaluate novel therapeutic strategies in experimental studies.

Functional MRI detects perfusion impairment in renal allografts with delayed graft function.

Delayed graft function (DGF) after kidney transplantation is not uncommon, and it is associated with long-term allograft impairment. Our aim was to compare renal perfusion changes measured with noninvasive functional MRI in patients early after kidney transplantation to renal function and allograft histology in biopsy samples. Forty-six patients underwent MRI 4-11 days after transplantation. Contrast-free MRI renal perfusion images were acquired using an arterial spin labeling technique. Renal function was assessed by estimated glomerular filtration rate (eGFR), and renal biopsies were performed when indicated within 5 days of MRI. Twenty-six of 46 patients had DGF. Of these, nine patients had acute rejection (including borderline), and eight had other changes (e.g., tubular injury or glomerulosclerosis). Renal perfusion was significantly lower in the DGF group compared with the group with good allograft function (231 ± 15 vs. 331 ± 15 ml·min(-1)·100 g(-1), P < 0.001). Living donor allografts exhibited significantly higher perfusion values compared with deceased donor allografts (P < 0.001). Renal perfusion significantly correlated with eGFR (r = 0.64, P < 0.001), resistance index (r = -0.57, P < 0.001), and cold ischemia time (r = -0.48, P < 0.01). Furthermore, renal perfusion impairment early after transplantation predicted inferior renal outcome and graft loss. In conclusion, noninvasive functional MRI detects renal perfusion impairment early after kidney transplantation in patients with DGF.

Quantification of Pulmonary Inflammation after Segmental Allergen Challenge Using Turbo-Inversion Recovery-Magnitude Magnetic Resonance Imaging

RATIONALE There is a need to develop novel noninvasive imaging biomarkers that help to evaluate antiinflammatory asthma treatments. OBJECTIVES To investigate whether the extent of the segmental lung edema measured noninvasively using turbo-inversion recovery-magnitude magnetic resonance imaging (TIRM MRI) corresponds to the severity of the regional allergic reaction determined by the percentage of eosinophils in bronchoalveolar lavage fluid (BAL) 24 hours after segmental allergen challenge in patients with asthma compared with normal control subjects. METHODS Eleven volunteers with allergic asthma and five healthy volunteers underwent segmental challenges with different allergen doses by two bronchoscopies 24 hours apart. They had lung MRI at baseline and 6 and 24 hours after segmental challenge. MRI TIRM scores were correlated with the eosinophilic response at 24 hours. MEASUREMENTS AND MAIN RESULTS In patients with asthma, there were significant differences of eosinophil percentages in BAL at 24 hours from segments given standard-dose, low-dose, or no allergen (saline) (P < 0.001). Correspondingly significant differences between the TIRM score in allergen standard-dose, low-dose, and saline-treated segments were observed at 24 hours post-challenge (P < 0.001). With increasing TIRM score at 24 hours the percent eosinophils per segment 24 hours post-challenge also increased accordingly (P < 0.001). There was interobserver agreement for TIRM score grading (kappa = 0.72 for 24-h time point). CONCLUSIONS The MRI-based noninvasive TIRM score is a promising biomarker for the noninvasive detection of the inflammatory response after segmental allergen challenge in patients with asthma and may serve to monitor the therapeutic effectiveness of novel antiinflammatory drugs in future human trials.

MR Imaging–derived Regional Pulmonary Parenchymal Perfusion and Cardiac Function for Monitoring Patients with Chronic Thromboembolic Pulmonary Hypertension before and after Pulmonary Endarterectomy

Purpose To evaluate surgical success after pulmonary endarterectomy (PEA) by means of cardiopulmonary magnetic resonance (MR) imaging. Materials and Methods In this institutional review board-approved study, 20 patients with chronic thromboembolic pulmonary hypertension were examined at 1.5 T with a dynamic contrast material-enhanced three-dimensional fast low-angle shot sequence before and 12 days after PEA (25th-75th percentile range, 11-16 days). Lung segments were evaluated visually before PEA for parenchymal hypoperfused segments. Pulmonary blood flow (PBF), first-pass bolus kinetic parameters, and biventricular mass and function were determined. Mean pulmonary artery pressure (mPAP) and 6-minute walking distance were measured before and after PEA. The Shapiro-Wilk test, paired two-sided Wilcoxon rank sum test, Spearman ρ correlation, and multiple linear regression analysis were performed. Results Two weeks after PEA, regional PBF increased 66% in the total lung from 32.7 to 54.2 mL/min/100 mL (P = .0002). However, after adjustment for cardiac output, this change was not evident anymore (increase of 7% from 7.03 to 7.54 mL/min/100 mL/L/min, P = .1). Only in the lower lobes, a significant increase in PBF after cardiac output adjustment remained: a 16% increase in the right lower lobe from 7.53 to 8.71 mL/min/100 mL (P = .01) and a 14% increase in the left lower lobe from 7.42 to 8.47 mL/min/100 mL/L/min (P < .05). Right ventricular mass and function also improved. mPAP decreased from 46 to 24 mm Hg (P < .0001). Six-minute walking distance increased from 390 to 467 m (P = .02) 5 months after PEA. Percentage change of mPAP and PBF in the lower lobe tended to be significant predictors of percentage change in 6-minute walking distance (β = -1.79 [P = .054] and β = 0.45 [P = .076], respectively) in multiple linear regression analysis. Conclusion Improvement of PBF after PEA was observed predominantly in the lower lungs, and the magnitude of improvement of PBF in the lower lobes correlated with the improvement in exercise capacity, reflecting surgical success. (©) RSNA, 2016.