The value of multimodal imaging with 123I-FP-CIT SPECT in differential diagnosis of dementia with Lewy bodies and Alzheimer's disease dementia

Abstract

Reduced nigrostriatal uptake on N-(3-fluoropropyl)-2β-carbomethoxy-3β-(4-[¹²³I]iodophenyl) nortropane (¹²³I-FP-CIT) SPECT reflects dopamine dysfunction, while other imaging markers could be complementary when used together. We assessed how well ¹²³I-FP-CIT SPECT differentiates dementia with Lewy bodies (DLBs) from Alzheimer's disease dementia (ADem) and whether multimodal imaging provides additional value. ¹²³I-FP-CIT SPECT, magnetic resonance imaging, [¹⁸F]2-fluoro-deoxy-D-glucose-positron emission tomography (PET), and ¹¹C-Pittsburgh compound B (PiB)-PET were assessed in 35 participants with DLBs and 14 participants with ADem (autopsy confirmation in 9 DLBs and 4 ADem). Nigrostriatal dopamine transporter uptake was evaluated with ¹²³I-FP-CIT SPECT using DaTQUANT software. Hippocampal volume was calculated with magnetic resonance imaging, cingulate island sign ratio with FDG-PET, and global cortical PiB retention with PiB-PET. The DaTQUANT z-scores of the putamen showed the highest c-statistic of 0.916 in differentiating DLBs from ADem among the analyzed imaging biomarkers. Adding another imaging modality to ¹²³I-FP-CIT SPECT had c-statistics ranging from 0.968 to 0.975, and ¹²³I-FP-CIT SPECT in combination with 2 other imaging modalities presented c-statistics ranging from 0.987 to 0.996. These findings suggest that multimodal imaging with ¹²³I-FP-CIT SPECT aids in differentiating DLBs and ADem and in detecting comorbid Lewy-related and Alzheimer's disease pathology in patients with DLBs and ADem.

Keywords: (123)I-FP-CIT SPECT; DaTQUANT; Dementia with Lewy bodies; FDG-PET; MRI; PiB-PET.

Figure 1.

Box-and-whisker plots showing the distribution of DaTQUANT z-scores by ¹²³I-FP-CIT SPECT for the putamen of DLB and ADem. ***p<0.001 for the difference between DLB and ADem (Student t-test). The cases with autopsy confirmation were numbered on the plots by the same case number as Table 3. Underlying pathology for Cases 1–7 were LBD, Cases 8–11 were LBD+AD, and Cases 12–13 were AD.

Figure 2.. Two imaging biomarkers scatter plots differentiating DLB from ADem

The plots (Blue: DLB, Red: ADem) represent distribution of the combination of the two imaging biomarkers from the followings: DaTQUANT putamen z-score, hippocampal volumes by MRI, CIS ratio by FDG-PET, and global PiB SUVr by PiB-PET. (A) DaTQUANT + MRI, (B) DaTQUANT + FDG, (C) DaTQUANT + PiB, (D) FDG + MRI, (E) MRI + PiB, (F) FDG + PiB The cases with autopsy confirmation were numbered on the plots by the same case number as Table 3. Underlying pathology for Cases 1–7 were LBD, Cases 8–11 were LBD+AD, and Cases 12–13 were AD.

Figure 3.. Three dimensional ellipsoid plots of the three imaging biomarkers differentiating DLB from ADem

A. ¹²³I-FP-CIT SPECT + FDG-PET + PiB-PET; B. ¹²³I-FP-CIT SPECT + MRI + FDG-PET; C. ¹²³I-FP-CIT SPECT + MRI + PiB-PET The plots show the distribution of the findings from the combination of the three imaging biomarkers from the following: DaTQUANT putamen z-score (“Putamen”), hippocampal volumes by MRI (“HP”), CIS ratio by FDG-PET (“CIS”), and global PiB SUVr by PiB-PET (“PIB”). Concentration ellipsoids represent 50% of the expected proportion of bivariate normal observations in each diagnostic group. A larger spherical ball represents imaging data that are closer to the viewer while smaller spheres represent data farther from the viewer. Red signifies ADem and blue LBD by diagnostic group prediction (concentration ellipsoids) and by individual diagnoses (balls). The cases with autopsy confirmation were numbered on the plots by the same case number as Table 3. Underlying pathology for Cases 1–7 were LBD, Cases 8–11 were LBD+AD, and Cases 12–13 were AD.