Diagnostic utility of ASL-MRI and FDG-PET in the behavioral variant of FTD and AD.

RESEARCH ARTICLE Diagnostic utility of ASL-MRI and FDG-PET in the behavioral variant of FTD and AD Duygu Tosun 1 , Norbert Schuff 1 , Gil D. Rabinovici 2 , Nagehan Ayakta 2,3 , Bruce L. Miller 2 , William Jagust 3 , Joel Kramer 2 , Michael M. Weiner 1 & Howard J. Rosen 2 Department of Radiology and Biomedical Imaging, University of California, San Francisco, California Memory and Aging Center, Department of Neurology, University of California, San Francisco, California School of Public Health, University of California, Berkeley, California Correspondence Duygu Tosun, Assistant Professor in Radiology and Biomedical Imaging, University of California, San Francisco (UCSF), Center for Imaging of Neurodegenerative Diseases (CIND) VA Medical Center, 4150 Clement St., Bldg 13, 114M, San Francisco, CA 94121. Tel: 415 221 4810 ext 3650; Fax: (415) 386-3954; E-mail: duygu.tosun@ucsf.edu Funding Information This work was supported by the National Institutes of Health Grant P01 AG019724-11, K24 AG045333, R01 AG032306, R01- AG038791, and P50 AG023501, The Hillblom Network, and the Department of Defense Grant W81XWH-05-2-0094. This work has also been made possible by use of research facilities at the Veteran Affairs Medical Center in San Francisco. Received: 3 May 2016; Revised: 6 June 2016; Accepted: 8 June 2016 Annals of Clinical and Translational Neurology 2016; 3(10): 740–751 Abstract Objective: To compare the values of arterial spin-labeled (ASL) MRI and fluo- rodeoxyglucose (FDG) PET in the diagnosis of behavioral variant of frontotem- poral dementia (bvFTD) and Alzheimer’s disease (AD). Methods: Partial least squares logistic regression was used to identify voxels with diagnostic value in cerebral blood flow (CBF) and cerebral metabolic rate of glucose (CMRgl) maps from patients with bvFTD (n = 32) and AD (n = 28), who were com- pared with each other and with cognitively normal controls (CN, n = 15). Diagnostic values of these maps were compared with each other. Results: Regions that differentiated each disorder from controls were similar for CBF and CMRgl. For differentiating AD from CN, the areas under the curve (AUC) for CBF (0.89) and CMRgl (0.91) were similar, with similar sensitivity (CBF: 86%, CMRgl: 78%) and specificity (CBF: 92%, CMRgl: 100%). Likewise, for differentiating bvFTD from CN performances of CBF (AUC = 0.83) and CMRgl (AUC = 0.85) were equivalent, with similar sensitivity (CBF: 78%, CMRgl: 79%) and specificity (CBF: 92%, CMRgl: 100%). In differentiating bvFTD from AD, classification was again similar for CBF (AUC = 0.87) and CMRgl (AUC = 0.79), as were sensitivity (CBF: 83%, CMRgl: 89%) and speci- ficity (CBF: 93%, CMRgl: 78%). None of the differences in any performance measure were statistically significant. Interpretation: ASL-MRI has similar diag- nostic utility as FDG-PET in the diagnosis of AD and bvFTD. Continued devel- opment of ASL-MRI as a diagnostic tool for neurodegenerative dementias is warranted. doi: 10.1002/acn3.330 Introduction Frontotemporal lobar degeneration (FTLD) is the second most common form of neurodegenerative dementia in the presenile population and the third most prevalent form of neurodegenerative dementia overall. 1,2 With an estimated prevalence of 15/100,000 in the age group of 45–64 years, FTLD represents a significant challenge for social welfare. 1,3 FTLD can present with a variety of syn- dromes, including progressive supranuclear palsy, corti- cobasal degeneration, and progressive aphasia, but the most common presentation is progressive change in per- sonality with abnormalities in socioemotional behavior, referred to as the behavioral variant of frontotemporal dementia (bvFTD). 4 Diagnosis of bvFTD remains diffi- cult, with patients being erroneously diagnosed with Alz- heimer’s disease (AD) or psychiatric disorders. 5–7 A large body of work has demonstrated that brain imaging, in particular structural magnetic resonance imaging (MRI) and functional imaging of cerebral blood flow (CBF) with SPECT or cerebral metabolic rate of glucose (CMRgl) with fluorodeoxyglucose (FDG) positron emission tomog- raphy (PET), can improve the accuracy of differential diagnosis in bvFTD. 8–17 These findings led the Center for Medicare and Medicaid Services (CMS) to approve FDG-PET as a diagnostic test for differentiating bvFTD a 2016 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals, Inc on behalf of American Neurological Association. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.