title: Quantitative susceptibility mapping of kidney inflammation and fibrosis in type 1 angiotensin receptor-deficient mice.
abstract: Disruption of the regulatory role of the kidneys leads to diverse renal pathologies; one major hallmark is inflammation and fibrosis. Conventional magnitude MRI has been used to study renal pathologies; however, the quantification or even detection of focal lesions caused by inflammation and fibrosis is challenging. We propose that quantitative susceptibility mapping (QSM) may be particularly sensitive for the identification of inflammation and fibrosis. In this study, we applied QSM in a mouse model deficient for angiotensin receptor type 1 (AT1). This model is known for graded pathologies, including focal interstitial fibrosis, cortical inflammation, glomerulocysts and inner medullary hypoplasia. We acquired high-resolution MRI on kidneys from AT1-deficient mice that were perfusion fixed with contrast agent. Two MR sequences were used (three-dimensional spin echo and gradient echo) to produce three image contrasts: T1, T2* (magnitude) and QSM. T1 and T2* (magnitude) images were acquired to segment major renal structures and to provide landmarks for the focal lesions of inflammation and fibrosis in the three-dimensional space. The volumes of major renal structures were measured to determine the relationship of the volumes to the degree of renal abnormalities and magnetic susceptibility values. Focal lesions were segmented from QSM images and were found to be closely associated with the major vessels. Susceptibilities were relatively more paramagnetic in wild-type mice: 1.46 ± 0.36 in the cortex, 2.14 ± 0.94 in the outer medulla and 2.10 ± 2.80 in the inner medulla (10(-2) ppm). Susceptibilities were more diamagnetic in knockout mice: -7.68 ± 4.22 in the cortex, -11.46 ± 2.13 in the outer medulla and -7.57 ± 5.58 in the inner medulla (10(-2) ppm). This result was consistent with the increase in diamagnetic content, e.g. proteins and lipids, associated with inflammation and fibrosis. Focal lesions were validated with conventional histology. QSM was very sensitive in detecting pathology caused by small focal inflammation and fibrosis. QSM offers a new MR contrast mechanism to study this common disease marker in the kidney.
authors.affiliation: Center for In Vivo Microscopy, Department of Radiology, Duke University Medical Center, Durham, NC, USA; Department of Biomedical Engineering, Duke University, Durham, NC, USA.
authors.forename: Luke
authors.initials: L
authors.lastname: Xie
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Sparks
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.forename: Yi
authors.initials: Y
authors.lastname: Qi
authors.forename: Chunlei
authors.initials: C
authors.lastname: Liu
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Coffman
authors.forename: G Allan
authors.initials: GA
authors.lastname: Johnson
mesh_terms: D000818:Animals; D003287:Contrast Media; D004198:Disease Susceptibility / Q000473:pathology*; D005355:Fibrosis / Q000473:pathology; D007091:Image Processing, Computer-Assisted; D007249:Inflammation / Q000473:pathology*; D007668:Kidney / Q000473:pathology*; D007672:Kidney Cortex / Q000473:pathology; D008279:Magnetic Resonance Imaging; D051379:Mice; D008810:Mice, Inbred C57BL; D044140:Receptor, Angiotensin, Type 1 / Q000172:deficiency* / Q000378:metabolism
chemical_list: D003287:Contrast Media; D044140:Receptor, Angiotensin, Type 1
keywords: AT1; fibrosis; inflammation; magnetic susceptibility; pathology; quantitative susceptibility mapping; renal structures; small animal preclinical imaging