Regional Lipid Expression Abnormalities Identified
Using MALDI IMS Correspond to MRI-Defined White Matter Hyperintensities
within Post-mortem Human Brain Tissues
posted on 2021-01-19, 17:11authored byWilliam Pinsky, Aaron Harris, Austyn D. Roseborough, Wenxuan Wang, Ali R. Khan, Kristina Jurcic, Ken K.-C. Yeung, Stephen H. Pasternak, Shawn N. Whitehead
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.