Liver Magnetic Resonance Spectroscopy as an Alternative for Evaluating Niemann-Pick C Disease Progression

Niemann-Pick disease (NP) is a group of rare genetic disorders that affect normal lipid metabolism and cause an accumulation of lipids in the liver, spleen, brain, and bone marrow. NP patients develop brain alterations and a very fast progression of liver damage. The purpose of this study is to characterize the changes in liver lipid composition during the progression of this disease using ex vivo magnetic resonance spectroscopy (MRS) in mouse models with the aim of identifying potential biomarkers to support a future non-invasive technique to follow-up these patients. NP type C (NPC) and wild-type (WT) mice were fed a chow diet and euthanized at 5 weeks of age (n = 5 per group) and 9 weeks of age (n = 5 per group). We extracted lipids from their livers and analyzed them with Gas Chromatography- Mass Spectrometry (GC-MS) and MRS. With the GC-MS analysis, 7 main fatty acids (FA) and cholesterols were quantified. Using MRS, we identified 5 metabolite peaks that correspond to FA only, 3 peaks that correspond to cholesterol only, and 2 peaks that correspond to FA and cholesterol. Our results show that the increase in liver cholesterol is the key biomarker for liver damage in NPC, which is consistent with a bad liver disease prognosis due to the association of increased cholesterol levels and liver inflammation. Additionally, we identified a difference in the pool of FA stored in the NPC compared to the WT mouse livers. Those different liver spectra could provide potential biomarkers for the noninvasive follow-up of NPC patients. © 2025 The Author(s).