Temporoparietal hypometabolism in frontotemporal lobar degeneration and associated imaging diagnostic errors

Abstract

Objective: To evaluate the cause of diagnostic errors in the visual interpretation of positron emission tomographic scans with fludeoxyglucose F 18 (FDG-PET) in patients with frontotemporal lobar degeneration (FTLD) and patients with Alzheimer disease (AD).

Design: Twelve trained raters unaware of clinical and autopsy information independently reviewed FDG-PET scans and provided their diagnostic impression and confidence of either FTLD or AD. Six of these raters also recorded whether metabolism appeared normal or abnormal in 5 predefined brain regions in each hemisphere-frontal cortex, anterior cingulate cortex, anterior temporal cortex, temporoparietal cortex, and posterior cingulate cortex. Results were compared with neuropathological diagnoses.

Setting: Academic medical centers.

Patients: Forty-five patients with pathologically confirmed FTLD (n=14) or AD (n=31).

Results: Raters had a high degree of diagnostic accuracy in the interpretation of FDG-PET scans; however, raters consistently found some scans more difficult to interpret than others. Unanimity of diagnosis among the raters was more frequent in patients with AD (27 of 31 patients [87%]) than in patients with FTLD (7 of 14 patients [50%]) (P=.02). Disagreements in interpretation of scans in patients with FTLD largely occurred when there was temporoparietal hypometabolism, which was present in 7 of the 14 FTLD scans and 6 of the 7 scans lacking unanimity. Hypometabolism of anterior cingulate and anterior temporal regions had higher specificities and positive likelihood ratios for FTLD than temporoparietal hypometabolism had for AD.

Conclusions: Temporoparietal hypometabolism in FTLD is common and may cause inaccurate interpretation of FDG-PET scans. An interpretation paradigm that focuses on the absence of hypometabolism in regions typically affected in AD before considering FTLD is likely to misclassify a significant portion of FTLD scans. Anterior cingulate and/or anterior temporal hypometabolism indicates a high likelihood of FTLD, even when temporoparietal hypometabolism is present. Ultimately, the accurate interpretation of FDG-PET scans in patients with dementia cannot rest on the presence or absence of a single region of hypometabolism but rather must take into account the relative hypometabolism of all brain regions.

Figure 1

Localization key and SSP images of 4 example PET scans with activity maps on the top row and z-maps showing deviation from a normal control cohort on the second row a) localization key of brain regions as used by the raters b) scan of a 66 y/o normal control subject and the color scale used for all PET images in the study. The local cerebral metabolic rate of glucose utilization (ICMRGlc) is indicated by the numbers along the top of the color scale and the z-score values are represented by the numbers across the bottom of the scale. c) scan of an AD subject with unanimous interpretations d) scan of an FTLD subject with unanimous interpretations e) scan of an FTLD subject with non-unanimous interpretations (Votes: 7 FTLD, 5 AD)

Figure 2

Histogram of the number of scans and the degree of unanimity in the interpretation. 0 raters with incorrect interpretations indicates unanimous interpretations. Only 50% of the FTLD scans had unanimous, correct interpretations. 87% of the AD scans had unanimous, correct interpretations. Of note, 2/4 AD scans with non-unanimous interpretations had only 1/12 raters in error.