ORCID Profile
0000-0002-9245-993X
Current Organisation
University of Liverpool
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Publisher: Springer Science and Business Media LLC
Date: 16-09-2019
DOI: 10.1007/S11307-019-01429-Z
Abstract: Purpose: To establish multi-modal imaging for the assessment of kidney pH, perfusion, and clearance rate using magnetic resonance imaging (MRI) and multispectral optoacoustic tomography (MSOT) in healthy mice. Kidney pH and perfusion values were measured on a pixel-by-pixel basis using the MRI acidoCEST and FAIR-EPI methods. Kidney filtration rate was measured by analyzing the renal clearance rate of IRdye 800 using MSOT. To test the effect of one imaging method on the other, a set of 3 animals were imaged with MSOT followed by MRI, and a second set of 3 animals were imaged with MRI followed by MSOT. In a subsequent study, the reproducibility of pH, perfusion, and renal clearance measurements were tested by imaging 4 animals twice, separated by 4 days. The contrast agents used for acidoCEST based pH measurements influenced the results of MSOT. Specifically, the exponential decay time from the kidney cortex, as measured by MSOT, was significantly altered when MRI was performed prior to MSOT. However, no significant difference in the cortex to pelvis area under the curve (AUC) was noted. When the order of experiments was reversed, no significant differences were noted in the pH or perfusion values. Reproducibility measurements demonstrated similar pH and cortex to pelvis AUC however, perfusion values were significantly different with the cortex values being higher and the pelvic values being lower in the second imaging time. We demonstrate that using a combination of MRI and MSOT, physiological measurements of pH, blood flow, and clearance rates can be measured in the mouse kidney in the same imaging session.
Publisher: Portland Press Ltd.
Date: 26-07-2010
DOI: 10.1042/BST0381062
Abstract: In the future, stem-cell-based therapies could offer new approaches to treat kidney disease and reduce the incidence of ESRD (end-stage renal disease), but, as yet, research in this area is only being conducted in rodents and it is not clear whether or when it could be applied to human patients. Drug therapies, on the other hand, have been very effective at delaying the progression of kidney disease, but, for various reasons, current drug regimes are not suitable for all patients. A greater understanding of the molecular mechanisms that underlie disease progression in chronic kidney disease could help to identify novel drug targets. However, progress in this area is currently hindered due to the lack of appropriate in vitro culture systems for important renal cell types, such as proximal tubule cells and podocytes. This problem could be overcome if it were possible to direct the differentiation of kidney stem cells to renal cell types in vitro. In the present review, we highlight the potential of surface gradients of small chemical functional groups to direct the differentiation of kidney stem cells.
Publisher: Springer Science and Business Media LLC
Date: 02-09-2015
DOI: 10.1038/SREP13601
Abstract: Maximising the use of preclinical murine models of progressive kidney disease as test beds for therapies ideally requires kidney function to be measured repeatedly in a safe, minimally invasive manner. To date, most studies of murine nephropathy depend on unreliable markers of renal physiological function, exemplified by measuring blood levels of creatinine and urea and on various end points necessitating sacrifice of experimental animals to assess histological damage, thus counteracting the principles of Replacement, Refinement and Reduction. Here, we applied two novel minimally invasive techniques to measure kidney function in SCID mice with adriamycin-induced nephropathy. We employed i) a transcutaneous device that measures the half-life of intravenously administered FITC-sinistrin, a molecule cleared by glomerular filtration and ii) multispectral optoacoustic tomography, a photoacoustic imaging device that directly visualises the clearance of the near infrared dye, IRDye 800CW carboxylate. Measurements with either technique showed a significant impairment of renal function in experimental animals versus controls, with significant correlations with the proportion of scarred glomeruli five weeks after induction of injury. These technologies provide clinically relevant functional data and should be widely adopted for testing the efficacies of novel therapies. Moreover, their use will also lead to a reduction in experimental animal numbers.
Location: United Kingdom of Great Britain and Northern Ireland
Location: United States of America
No related grants have been discovered for Bettina Wilm.