Unveiling metabolic patterns in dementia: Insights from high-resolution quantitative blood-oxygenation-level-dependent MRI.

Abstract

Oxygen extraction fraction (OEF) and deoxyhemoglobin (DoHb) levels reflect variations in cerebral oxygen metabolism in demented patients. Delineating the metabolic profiles evident throughout different phases of dementia necessitates an integrated analysis of OEF and DoHb levels. This is enabled by leveraging high-resolution quantitative blood oxygenation level dependent (qBOLD) analysis of magnitude images obtained from a multi-echo gradient-echo MRI (mGRE) scan performed on a 3.0 Tesla scanner. Achieving superior spatial resolution in qBOLD necessitates the utilization of an mGRE scan with only four echoes, which in turn limits the number of measurements compared to the parameters within the qBOLD model. Consequently, it becomes imperative to discard non-essential parameters to facilitate further analysis. This process entails transforming the qBOLD model into a format suitable for fitting the log-magnitude difference (L-MDif) profiles of the four echo magnitudes present in each brain voxel. In order to bolster spatial specificity, the log-difference qBOLD model undergoes refinement into a representative form, termed as r-qBOLD, particularly when applied to class-averaged L-MDif signals derived through k-means clustering of L-MDif signals from all brain voxels into a predetermined number of clusters. The agreement between parameters estimated using r-qBOLD for different cluster sizes is validated using Bland-Altman analysis, and the model's goodness-of-fit is evaluated using a -test. Retrospective MRI data of Alzheimer's disease (AD), mild cognitive impairment (MCI), and non-demented patients without neuropathological disorders, pacemakers, other implants, or psychiatric disorders, who completed a minimum of three visits prior to MRI enrolment, are utilized for the study. Utilizing a cohort comprising 30 demented patients aged 65-83 years in stages 4-6 representing mild, moderate, and severe stages according to the clinical dementia rating (CDR), matched with an age-matched non-demented control group of 18 individuals, we conducted joint observations of OEF and DoHb levels estimated using r-qBOLD. The observations elucidate metabolic signatures in dementia based on OEF and DoHb levels in each voxel. Our principal findings highlight the significance of spatial patterns of metabolic profiles (metabolic patterns) within two distinct regimes: OEF levels exceeding the normal range (S1-regime), and OEF levels below the normal range (S2-regime). The S1-regime, accompanied by low DoHb levels, predominantly manifests in fronto-parietal and perivascular regions with increase in dementia severity. Conversely, the S2-regime, accompanied by low DoHb levels, is observed in medial temporal (MTL) regions. Other regions with abnormal metabolic patterns included the orbitofrontal cortex (OFC), medial-orbital prefrontal cortex (MOPFC), hypothalamus, ventro-medial prefrontal cortex (VMPFC), and retrosplenial cortex (RSP). Dysfunction in the OFC and MOPFC indicated cognitive and emotional impairment, while hypothalamic involvement potentially indicated preclinical dementia. Reduced metabolic activity in the RSP suggested early-stage AD related functional abnormalities. Integrated analysis of OEF and DoHb levels using r-qBOLD reveals distinct metabolic signatures across dementia phases, highlighting regions susceptible to neuronal loss, vascular involvement, and preclinical indicators.