Ventra. Validation Study of the Ventricle Feature Estimation and Classification Tool to Differentiate Behavioral Variant Frontotemporal Dementia from Psychiatric Disorders and Other Degenerative Diseases

Introduction Lateral ventricles are reliable and sensitive indicators of brain atrophy and disease progression in behavioral variant frontotemporal dementia (bvFTD). Here we validate our previously developed automated tool using ventricular features (known as VentRa) for the classification of bvFTD vs a mixed cohort of neurodegenerative, vascular, and psychiatric disorders from a clinically representative independent dataset. Methods Lateral ventricles were segmented for 1110 subjects - 14 bvFTD, 30 other Frontotemporal Dementia (FTD), 70 Lewy Body Disease (LBD), 898 Alzheimer Disease (AD), 62 Vascular Brain Injury (VBI) and 36 Primary Psychiatric Disorder (PPD) from the publicly accessible National Alzheimer’s Coordinating Center dataset to assess the performance of VentRa. Results Using ventricular features to discriminate bvFTD subjects from PPD, VentRa achieved an accuracy of 84%, 71% sensitivity and 89% specificity. VentRa was able to identify bvFTD from a mixed age-matched cohort (i.e., Other FTD, LBD, AD, VBI and PPD) and to correctly classify other disorders as ‘not compatible with bvFTD’ with a specificity of 83%. The specificity against each of the other individual cohorts were 80% for other FTD, 83% for LBD, 83% for AD and 84% for VBI. Discussion VentRa is a robust and generalizable tool with potential usefulness for improving the diagnostic certainty of bvFTD, particularly for the differential diagnosis with PPD. ### Competing Interest Statement Competing interests: Dr. Manera reports no disclosures Dr. Dadar reports no disclosures Dr. Collins is co-founder of True Positive Medical Devices. Dr. Ducharme receives salary funding from the Fonds de Recherche du Quebec - Sante. Dr. Ducharme is the co-founder of Arctic Fox AI. ### Funding Statement This study did not receive any funding ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The data sample used for this study was obtained from the National Alzheimers Coordinating Centers Uniform Data Set (NACC). The NACC developed a database of standardized clinical research data obtained from past and present National Institute on Aging (NIA)-funded Alzheimers Disease Research Centers across the United States. NACC data collection has been previously described in Morris JC, Weintraub S, Chui HC, et al. The Uniform Data Set (UDS): clinical and cognitive variables and descriptive data from Alzheimer Disease Centers. Alzheimer Dis Assoc Disord 2006;20(4):210-6. doi: 10.1097/01.wad.0000213865.09806.92 I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors. Complete NACC dataset can be obtained upon request (https://naccdata.org/requesting-data/data-request-process) * bvFTD : Behavioral Variant Frontotemporal Dementia PPD : Primary Psychiatric Disorder DBM : deformation-based morphometry CN : normal controls APR : anteroposterior ratio MCI : mild cognitive impairment AD : Alzheimer’s dementia FTD : Frontotemporal Dementia TVV : total ventricular volume LRFR : left-right frontal ratio LRTR : left-right temporal ratio NACC : National Alzheimer’s Coordinating Center dataset LBD : Lewy Body Disease VBI : Vascular Brain Injury T1w : T1-weighted (T1w) TFE : Turbo Field Echo FSE : Fast spin echo FSPGR : fast spoiled gradient-echo MPRAGE : Magnetization Prepared - RApid Gradient Echo MMSE : Mini-Mental Status Examination CDR : Clinical Dementia Rating CDR-SB : Clinical Dementia Rating-Sum of Boxes LR : Likelihood ratios FN : False negatives TP : True positives FP : False positives ROI : Region of Interest