PMID- 33464828 OWN - NLM STAT- MEDLINE VI - 93 IP - 4 TI - Regional Lipid Expression Abnormalities Identified Using MALDI IMS Correspond to MRI-Defined White Matter Hyperintensities within Post-mortem Human Brain Tissues. PG - 2652-2659 LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Anal Chem JT - Analytical chemistry JID - 0370536 IS - 1520-6882 (Electronic) LID - 10.1021/acs.analchem.0c05017 [doi] FAU - Pinsky, William AU - Pinsky W AUID- ORCID: 0000-0002-0933-8468 AD - Vulnerable Brain Lab, Department of Anatomy and Cell Biology, University of Western Ontario, London, N6A 5C1 Ontario, Canada. FAU - Harris, Aaron AU - Harris A AD - Vulnerable Brain Lab, Department of Anatomy and Cell Biology, University of Western Ontario, London, N6A 5C1 Ontario, Canada. FAU - Roseborough, Austyn D AU - Roseborough AD AD - Vulnerable Brain Lab, Department of Anatomy and Cell Biology, University of Western Ontario, London, N6A 5C1 Ontario, Canada. FAU - Wang, Wenxuan AU - Wang W AD - Vulnerable Brain Lab, Department of Anatomy and Cell Biology, University of Western Ontario, London, N6A 5C1 Ontario, Canada. FAU - Khan, Ali R AU - Khan AR AD - Department of Medical Biophysics, University of Western Ontario, London, N6A 5C1 Ontario, Canada. FAU - Jurcic, Kristina AU - Jurcic K AD - MALDI Mass Spectrometry Facility, Department of Biochemistry, University of Western Ontario, London, N6A 5C1 Ontario, Canada. FAU - Yeung, Ken K-C AU - Yeung KK AUID- ORCID: 0000-0001-6933-2941 AD - Departments of Biochemistry and Chemistry, University of Western Ontario, London, N6A 5C1 Ontario, Canada. FAU - Pasternak, Stephen H AU - Pasternak SH AD - Robarts Research Institute, Western University, London, N6A 3K7 Ontario, Canada. FAU - Whitehead, Shawn N AU - Whitehead SN AUID- ORCID: 0000-0003-4728-8067 AD - Vulnerable Brain Lab, Department of Anatomy and Cell Biology, University of Western Ontario, London, N6A 5C1 Ontario, Canada. IS - 0003-2700 (Linking) RN - 0 (Lipids) SB - IM MH - Brain/*pathology MH - Diagnosis MH - Humans MH - Lipids/*chemistry MH - *Magnetic Resonance Imaging MH - Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization/*methods MH - White Matter/metabolism/*pathology DCOM- 20210226 LR - 20210226 DP - 20210202 DEP - 20210119 AB - Periventricular white matter hyperintensities (pvWMHs) are a neurological feature detected with magnetic resonance imaging that are clinically associated with an increased risk of stroke and dementia. pvWMHs represent white matter lesions characterized by regions of myelin and axon rarefaction and as such likely involve changes in lipid composition; however, these alterations remain unknown. Lipids are critical in determining cell function and survival. Perturbations in lipid expression have previously been associated with neurological disorders. Matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry (IMS) is an emerging technique for untargeted, high-throughput investigation of lipid expression and spatial distribution in situ; however, the use of MALDI IMS has been previously been limited by the need for non-embedded, non-fixed, fresh-frozen samples. In the current study, we demonstrate the novel use of MALDI IMS to distinguish regional lipid abnormalities that correlate with magnetic resonance imaging (MRI) defined pvWMHs within ammonium formate washed, formalin-fixed human archival samples. MALDI IMS scans were conducted in positive or negative ion detection mode on tissues sublimated with 2,5-dihydroxybenzoic acid or 1,5-diaminonaphthalene matrices, respectively. Using a broad, untargeted approach to lipid analysis, we consistently detected 116 lipid ion species in 21 tissue blocks from 11 different post-mortem formalin-fixed human brains. Comparing the monoisotopic mass peaks of these lipid ions elucidated significant differences in lipid expression between pvWMHs and NAWM for 31 lipid ion species. Expanding our understanding of alterations in lipid composition will provide greater knowledge of molecular mechanisms underpinning ischemic white matter lesions and provides the potential for novel therapeutic interventions targeting lipid composition abnormalities.