Browsing by Author "McCarthy, Brian"

Now showing 1 - 2 of 2
  • Thumbnail Image
    Item
    Functional MRI Assessment of Renal Fibrosis in Rat Models
    (Office of the Vice Chancellor for Research, 2015-04-17) Jiang, Lei; Lin, Chen; Territo, Paul R; Riley, Amanda; McCarthy, Brian; Molitoris, Bruce A.; Hutchins, Gary D.
    Introduction Renal fibrosis is a common consequence of chronic kidney diseases which affects a large population. Therefore, it is important to establish imaging based noninvasive biomarkers to monitor the progression or regression of renal fibrosis instead of biopsy. Magnetic resonance imaging (MRI) could provide both high spatial resolution and excellent tissue contrast for visualization of kidney morphology. Moreover, MRI is capable of assessing pseudo perfusion (Df) and perfusion fraction (Pf) with intra-voxel incoherent motion (IVIM) imaging (1), tissue oxygenation with T2* mapping (2), macromolecular composition with T1rho imaging (3) and kidney function (eGFR) with dynamic contrast enhanced (DCE) imaging (4). This study is aimed to evaluate the sensitivity of these MRI techniques to the renal fibrotic changes in a rat model. Methods A total of 4 rats were scanned at early (2-5 days) and late (25-35 days) time points after surgical intervention (unilateral ureteral obstruction to induce renal fibrosis) on a Siemens Tim Trio 3T scanner using an 80mm inner diameter 8-channel rat body coil (RAPID, USA) under a stable anesthetized condition. Axial images of 80mm FOV, 2mm slice thick and sub-millimeter in-place resolution were acquired for different functional MRI techniques with following parameters, respectively: IVIM with10 b-values of 0 - 750 s/mm2. T2*: with 10 TEs of 8 - 66 ms; T1rho: with 9 TSL times of 5 - 80 ms; DCE: with150 dynamic measurements at a temporal resolution of 1.01 s. before and after a 15s injection of 1.1 ml GD-DTPA through rat tail with a power injector. Functional data were processed and analyzed using custom MATLAB programs or analysis tools installed in the MRI console workstation. Results Figure 1 shows an anatomical image of the obstructed (R) and healthy (L) rat kidneys. Figures 2-4 show example T1rho map, IVIM Df map, and T2* map, respectively. Quantitative results based on ROI measurements are summarized in table 1. Changes consistent with the expected progression of fibrosis were observed in the obstructed kidney (R) while the healthy kidney (L) and muscle region remained stable. Figure 5 shows the DCE-MRI images at baseline as well as 45s, 95s and 240s after contrast infusion. The timing and intensity of signal changes are clearly different between two kidneys. Quantitative results of DCE-MRI data and comparison with PET study is reported in a separate abstract. Discussion High quality anatomical and functional images of rat kidney can be obtained on a clinical 3.0T MR scanner with dedicated small animal coils and optimized imaging techniques. The findings suggest that IVIM, T2*, T1rho and DCE can be used to assess and monitor different aspects of physiological changes in kidney fibrosis.
  • Thumbnail Image
    Item
    Hydrocephalus in a rat model of Meckel Gruber syndrome with a TMEM67 mutation
    (Springer Nature, 2019-01-31) Shim, Joon W.; Territo, Paul R.; Simpson, Stefanie; Watson, John C.; Jiang, Lei; Riley, Amanda A.; McCarthy, Brian; Persohn, Scott; Fulkerson, Daniel; Blazer-Yost, Bonnie L.; Biology, School of Science
    Transmembrane protein 67 (TMEM67) is mutated in Meckel Gruber Syndrome type 3 (MKS3) resulting in a pleiotropic phenotype with hydrocephalus and renal cystic disease in both humans and rodent models. The precise pathogenic mechanisms remain undetermined. Herein it is reported for the first time that a point mutation of TMEM67 leads to a gene dose-dependent hydrocephalic phenotype in the Wistar polycystic kidney (Wpk) rat. Animals with TMEM67 heterozygous mutations manifest slowly progressing hydrocephalus, observed during the postnatal period and continuing into adulthood. These animals have no overt renal phenotype. The TMEM67 homozygous mutant rats have severe ventriculomegaly as well as severe polycystic kidney disease and die during the neonatal period. Protein localization in choroid plexus epithelial cells indicates that aquaporin 1 and claudin-1 both remain normally polarized in all genotypes. The choroid plexus epithelial cells may have selectively enhanced permeability as evidenced by increased Na+, K+ and Cl- in the cerebrospinal fluid of the severely hydrocephalic animals. Collectively, these results suggest that TMEM67 is required for the regulation of choroid plexus epithelial cell fluid and electrolyte homeostasis. The Wpk rat model, orthologous to human MKS3, provides a unique platform to study the development of both severe and mild hydrocephalus.