A discriminative event-based model for subtype diagnosis of sporadic Creutzfeldt-Jakob disease using brain MRI

Vikram Venkatraghavan, Riccardo Pascuzzo*, Esther E. Bron, Marco Moscatelli, Marina Grisoli, Amy Pickens, Mark L. Cohen, Lawrence B. Schonberger, Pierluigi Gambetti, Brian S. Appleby, Stefan Klein, Alberto Bizzi

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

4 Citations (Scopus)
27 Downloads (Pure)

Abstract

Introduction: Sporadic Creutzfeldt-Jakob disease (sCJD) comprises multiple subtypes (MM1, MM2, MV1, MV2C, MV2K, VV1, and VV2) with distinct disease durations and spatiotemporal cascades of brain lesions. Our goal was to establish the ante mortem diagnosis of sCJD subtype, based on patient-specific estimates of the spatiotemporal cascade of lesions detected by diffusion-weighted magnetic resonance imaging (DWI). Methods: We included 488 patients with autopsy-confirmed diagnosis of sCJD subtype and 50 patients with exclusion of prion disease. We applied a discriminative event-based model (DEBM) to infer the spatiotemporal cascades of lesions, derived from the DWI scores of 12 brain regions assigned by three neuroradiologists. Based on the DEBM cascades and the prion protein genotype at codon 129, we developed and validated a novel algorithm for the diagnosis of the sCJD subtype. Results: Cascades of MM1, MM2, MV1, MV2C, and VV1 originated in the parietal cortex and, following subtype-specific orderings of propagation, went toward the striatum, thalamus, and cerebellum; conversely, VV2 and MV2K cascades showed a striatum-to-cortex propagation. The proposed algorithm achieved 76.5% balanced accuracy for the sCJD subtype diagnosis, with low rater dependency (differences in accuracy of ± 1% among neuroradiologists). Discussion: Ante mortem diagnosis of sCJD subtype is feasible with this novel data-driven approach, and it may be valuable for patient prognostication, stratification in targeted clinical trials, and future therapeutics. Highlights: Subtype diagnosis of sporadic Creutzfeldt-Jakob disease (sCJD) is achievable with diffusion MRI. Cascades of diffusion MRI abnormalities in the brain are subtype-specific in sCJD. We proposed a diagnostic algorithm based on cascades of diffusion MRI abnormalities and demonstrated that it is accurate. Our method may aid early diagnosis, prognosis, stratification in clinical trials, and future therapeutics. The present approach is applicable to other neurodegenerative diseases, enhancing the differential diagnoses.

Original languageEnglish
Pages (from-to)3261-3271
Number of pages11
JournalAlzheimer's and Dementia
Volume19
Issue number8
Early online date7 Feb 2023
DOIs
Publication statusPublished - Aug 2023

Bibliographical note

Funding Information:
V.V., R.P., S.K., and A.B. have received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement No. 666992. A.B. has received funding from the CJD Foundation (CJD Foundation Grant, Strides for CJD Grant, Walter Williams Memorial Research Grant, Sherry Maxwell Fabian Memorial Grant, Jeffrey A. Smith Memorial Research Grant). M.L.C. and B.S.A. are supported by CDC NU2GCK000434. This work was partially supported by the Italian Ministry of Health (RRC). The funding sources had no involvement in study design, in the collection, analysis, and interpretation of data, in the writing of the report, nor in the decision to submit the article for publication. The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention, Atlanta, Georgia, USA. Open access funding provided by BIBLIOSAN.

Funding Information:
V.V., R.P., S.K., and A.B. have received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement No. 666992. A.B. has received funding from the CJD Foundation (CJD Foundation Grant, Strides for CJD Grant, Walter Williams Memorial Research Grant, Sherry Maxwell Fabian Memorial Grant, Jeffrey A. Smith Memorial Research Grant). M.L.C. and B.S.A. are supported by CDC NU2GCK000434. This work was partially supported by the Italian Ministry of Health (RRC). The funding sources had no involvement in study design, in the collection, analysis, and interpretation of data, in the writing of the report, nor in the decision to submit the article for publication.

Funding Information:
B.S. Appleby: Has received research funding from CDC, NIH, Ionis, and Alector. Consulting for Acadia, Ionis, and Sangamo. Received royalties from Wolters Kluwer. Received payment for expert testimony for Kaufman & Canoles. Received support for meetings/travel from the CJD Foundation. Holds unpaid leadership roles for the Alzheimer's Association and CJD Foundation.

Publisher Copyright:
© 2023 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.

Fingerprint

Dive into the research topics of 'A discriminative event-based model for subtype diagnosis of sporadic Creutzfeldt-Jakob disease using brain MRI'. Together they form a unique fingerprint.

Cite this