Brain PET Imaging: Frontotemporal Dementia

Abstract

Brain PET adds value in diagnosing neurodegenerative disorders, especially frontotemporal dementia (FTD) due to its syndromic presentation that overlaps with a variety of other neurodegenerative and psychiatric disorders. 18F-FDG-PET has improved sensitivity and specificity compared with structural MR imaging, with optimal diagnostic results achieved when both techniques are utilized. PET demonstrates superior sensitivity compared with SPECT for FTD diagnosis that is primarily a supplement to other imaging and clinical evaluations. Tau-PET and amyloid-PET primary use in FTD diagnosis is differentiation from Alzheimer disease, although these methods are limited mainly to research settings.

Keywords: (18)F-FDG-PET; Alzheimer disease (AD); Amyloid-PET; Frontotemporal dementia (FTD); MRI; Neurodegenerative disorders fused-in-sarcoma protein (FUS); SPECT; Tau-PET.

Fig. 1.

Structural MR imaging of a person with advanced FTD. There is marked atrophy of the frontotemporal lobes bilaterally. However, the parietooccipital lobe is comparatively preserved.

Fig. 2.

Differential patterns of hypometabolism on FDG-PET z-score maps in neurodegenerative disease. Blue and purple colors denote areas of the FDG-PET scan that are −2 standard deviations or more below the mean of the control comparison group. There is temporoparietal hypometabolism in AD, marked occipital hypometabolism in DLB, predominantly frontal hypometabolism in FTD, and asymmetric hypometabolism in CBD. From Brown RK, Bohnen NI, Wong KK, Minoshima S, Frey KA. Brain PET in suspected dementia: patterns of altered FDG metabolism. Radiographics: a Review Publication of the Radiological Society of North America, Inc. 2014 May-Jun;34(3):684–701.

Fig. 3.

Axial brain FDG-PET uptake in representative participants displayed in neurologic orientation (right side of the image is on reader’s right-hand side). The clinically normal participant shows uniform Food and Drug Administration uptake throughout the brain as illustrated by the widespread intense bright colors. The person with clinical AD shows early asymmetric frontal and temporal hypometabolism that is comparatively more advanced in a person with bvFTD. (Adapted from Tosun D, Schuff N, Rabinovici GD, Ayakta N, Miller BL, Jagust W, Kramer J, Weiner MM, Rosen HJ. Diagnostic utility of ASL-MRI and FDG-PET in the behavioral variant of FTD and AD. Ann Clin Transl Neurol. 2016 Aug 30;3(10):740–751.)

Fig. 4.

Visual assessment of brain perfusion in a patient with AD using SPECT. There is hypoperfusion in the parietal lobes bilaterally. (From Valotassiou, V, Tsougos, I, Tzavara, C, Georgoulias, P, Papatriantafyllou, J, Karageorgiou, C, Sifakis, N, & Zerva, C (2009). Evaluation of brain perfusion in specific Brodmann areas in Frontotemporal dementia and Alzheimer disease using automated 3-D voxel based analysis. Journal of Instrumentation, 4(05), P05020.)

Fig. 5.

Visual assessment of brain perfusion in a patient with FTD using SPECT. There is slightly asymmetric hypoperfusion in the frontal lobes, favoring the right side. (From Valotassiou, V, Tsougos, I, Tzavara, C, Georgoulias, P, Papatriantafyllou, J, Karageorgiou, C, Sifakis, N, & Zerva, C (2009). Evaluation of brain perfusion in specific Brodmann areas in Frontotemporal dementia and Alzheimer disease using automated 3-D voxel based analysis. Journal of Instrumentation, 4(05), P05020.)

Fig. 6.

Example of hypoperfusion on SPECT in a person with bvFTD. There is bifrontal and bitemporal hypoperfusion. Reprinted from J Alzheimers Dis. 30(4), Rollin-Sillaire A, Bombois S, Deramecourt V, et al. Contribution of single photon emission computed tomography to the differential diagnosis of dementia in a memory clinic, 833–845. Copyright 2012, with permission from IOS Press. The publication is available at IOS Press through http://dx.doi.org/10.3233/JAD-2012-111067.

Fig. 7.

Amyloid and FDG-PET abnormalities across normal cognition, AD, and FTD variants (lvPPA, logopenic variant primary progressive aphasia; bvFTD, and svPPA). DVR, distribution volume ratio; NC, normal controls; SUVR, standardized uptake value ratio. There is a comparative lack of amyloid uptake in the FTD syndromes. (From Laforce R Jr, Rabinovici GD. Amyloid imaging in the differential diagnosis of dementia: review and potential clinical applications. Alzheimers Res Ther. 2011;3(6):31. Published 2011 Nov 10.)

Fig. 8.

MR imaging (left) and ¹⁸F-T807 PET (right) brain images from a 56-year-old person with P301L MAPT mutation FTD. Visually apparent frontal and temporal atrophy is noted on MR imaging along with increased tau uptake in the basal ganglia. (From Ghetti B, Oblak AL, Boeve BF, Johnson KA, Dickerson BC, Goedert M. Invited review: Frontotemporal dementia caused by microtubule-associated protein tau gene (MAPT) mutations: a chameleon for neuropathology and neuroimaging [published correction appears in Neuropathol Appl Neurobiol. 2015 Jun;41(4):571] [published correction appears in Neuropathol Appl Neurobiol. 2015 Jun;41(4):571]. Neuropathol Appl Neurobiol. 2015;41(1):24–46.)

Fig. 9.

nTRD22, a novel small molecule that allosterically modulates TDP-43 and may serve as a binding domain for new tau PET tracers. From Rao PPN, Shakeri A, Zhao Y, Calon F. Strategies in the design and development of (TAR) DNA-binding protein 43 (TDP-43) binding ligands. Eur J Med Chem. 2021;225:113753.