Post mortem analysis of hepatic volume and lipid content by magnetic resonance imaging and spectroscopy in fixed murine neonates.

Autor: Jonuscheit M; Institute for Clinical Diabetology, German Diabetes Center, Leibniz Institute for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany.; German Center for Diabetes Research (DZD e.V.), München-Neuherberg, Germany., Uhlemeyer C; German Center for Diabetes Research (DZD e.V.), München-Neuherberg, Germany.; Institute for Vascular and Islet Cell Biology, German Diabetes Center, Leibniz Institute for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany., Korzekwa B; Institute for Clinical Diabetology, German Diabetes Center, Leibniz Institute for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany.; German Center for Diabetes Research (DZD e.V.), München-Neuherberg, Germany., Schouwink M; University Children's Hospital, Heinrich Heine University Düsseldorf, Düsseldorf, Germany., Öner-Sieben S; Institute of Child Nutrition, Max Rubner-Institut, Federal Research Institute of Nutrition and Food, Karlsruhe, Germany., Ensenauer R; Institute of Child Nutrition, Max Rubner-Institut, Federal Research Institute of Nutrition and Food, Karlsruhe, Germany., Roden M; Institute for Clinical Diabetology, German Diabetes Center, Leibniz Institute for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany.; German Center for Diabetes Research (DZD e.V.), München-Neuherberg, Germany.; Department of Endocrinology and Diabetology, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, Düsseldorf, Germany., Belgardt BF; German Center for Diabetes Research (DZD e.V.), München-Neuherberg, Germany.; Institute for Vascular and Islet Cell Biology, German Diabetes Center, Leibniz Institute for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany., Schrauwen-Hinderling VB; Institute for Clinical Diabetology, German Diabetes Center, Leibniz Institute for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany.; German Center for Diabetes Research (DZD e.V.), München-Neuherberg, Germany.; Department of Radiology and Nuclear Medicine, Maastricht University Medical Center, Maastricht, The Netherlands.
Jazyk: angličtina
Zdroj: NMR in biomedicine [NMR Biomed] 2024 Aug; Vol. 37 (8), pp. e5140. Date of Electronic Publication: 2024 Mar 31.
DOI: 10.1002/nbm.5140
Abstrakt: Maternal obesity and hyperglycemia are linked to an elevated risk for obesity, diabetes, and steatotic liver disease in the adult offspring. To establish and validate a noninvasive workflow for perinatal metabolic phenotyping, fixed neonates of common mouse strains were analyzed postmortem via magnetic resonance imaging (MRI)/magnetic resonance spectroscopy (MRS) to assess liver volume and hepatic lipid (HL) content. The key advantage of nondestructive MRI/MRS analysis is the possibility of further tissue analyses, such as immunohistochemistry, RNA extraction, and even proteomics, maximizing the data that can be gained per individual and therefore facilitating comprehensive correlation analyses. This study employed an MRI and 1 H-MRS workflow to measure liver volume and HL content in 65 paraformaldehyde-fixed murine neonates at 11.7 T. Liver volume was obtained using semiautomatic segmentation of MRI acquired by a RARE sequence with 0.5-mm slice thickness. HL content was measured by a STEAM sequence, applied with and without water suppression. T 1 and T 2 relaxation times of lipids and water were measured for respective correction of signal intensity. The HL content, given as CH 2 /(CH 2  + H 2 O), was calculated, and the intrasession repeatability of the method was tested. The established workflow yielded robust results with a variation of ~3% in repeated measurements for HL content determination. HL content measurements were further validated by correlation analysis with biochemically assessed triglyceride contents (R 2  = 0.795) that were measured in littermates. In addition, image quality also allowed quantification of subcutaneous adipose tissue and stomach diameter. The highest HL content was measured in C57Bl/6N (4.2%) and the largest liver volume and stomach diameter in CBA (53.1 mm 3 and 6.73 mm) and NMRI (51.4 mm 3 and 5.96 mm) neonates, which also had the most subcutaneous adipose tissue. The observed effects were independent of sex and litter size. In conclusion, we have successfully tested and validated a robust MRI/MRS workflow that allows assessment of morphology and HL content and further enables paraformaldehyde-fixed tissue-compatible subsequent analyses in murine neonates.
(© 2024 The Authors. NMR in Biomedicine published by John Wiley & Sons Ltd.)
Databáze: MEDLINE