PROGNOSTIC VALUE OF REGIONAL PERFUSION ABNORMALITY ON HMPAO-SPECT IN COGNITIVE IMPAIRMENT AND DEMENTIA

Abstract

Background: Cerebral atrophy has the potential to be a diagnostic biomarker of the behavioural variant frontotemporal dementia (bvFTD), but current imaging methods are limited when detecting subtle early-disease changes. Using deformation-based morphometry (DBM) and relying on robust registration methods, we aimed to precisely measure changes in the pattern of atrophy in patients with bvFTD compared to cognitively normal controls (CN) to develop a data-driven MRI biomarker. Methods: T1weighted magnetic resonance imaging scans from 70 bvFTD patients (152 timepoints) and 123 age-matched CN (245 timepoints) obtained from the frontotemporal lobar degeneration neuroimaging initiative (NIFD) were pre-processed using denoising, image intensity non-uniformity correction, intensity range normalization and stereotaxic registration. Afterwards, they were non-linearly warped to an average template brain of 152 healthy young individuals (MNI-ICBM_152). Avoxel-wise mixed effects model analysis was performed, where the Jacobian determinant from the DBM analysis (as a proxy of local atrophy) was the dependent variable and age, sex, and diagnosis were the independent fixed variables. The model also included an interaction term between diagnosis and age. The resulting maps were corrected for multiple comparisons using False Discovery Rate (FDR), thresholded at 0.05. Results: Fig.1 shows the statistically significant difference in atrophy pattern bvFTD and CN, with greater atrophy in the medial portions of the frontal lobes, insula, basal ganglia, medial and anterior temporal regions bilaterally and regions of brainstem and cerebellum in bvFTD, as previously reported in pathological and cross-sectional morphometric studies. A corresponding volume increase was also found in the ventricles and sulci, mainly in frontal horns and lateral sulcus. In terms of the longitudinal change, both bvFTD and CN showed diffuse progressive volume loss due to ageing (Fig.2). Over a brief follow up period (mean 0.75y for bvFTD and 0.71y for CN), the enlargement of the frontal horns of the ventricles was the most significant differentiator between bvFTD from CN (Fig.3). Conclusions: This data-driven pattern of longitudinal changes will be used to develop an MRIbiomarker to not only differentiate bvFTD patients from CN, but may eventually allow to differentiate them from primary psychiatric disorders and other dementias with potential application at an individual patient level. P1-332 PROGNOSTIC VALUE OF REGIONAL PERFUSION ABNORMALITY ON HMPAOSPECT IN COGNITIVE IMPAIRMENTAND DEMENTIA