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Ming-Kai Chen

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3 papers

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YNICL Journal 2023 Journal Article

Principal component analysis of synaptic density measured with [11C]UCB-J PET in early Alzheimer’s disease

Ryan S. O'Dell
Albert Higgins-Chen
Dhruva Gupta
Ming-Kai Chen
Mika Naganawa
Takuya Toyonaga
Yihuan Lu
Gessica Ni

BACKGROUND: C]UCB-J PET and assessed the association between principal components (PC) subject scores with cognitive performance. METHODS: C]UCB-J binding was measured in 45 amyloid + participants with AD and 19 amyloid- cognitively normal participants aged 55-85. A validated neuropsychological battery assessed performance across five cognitive domains. PCA was applied to the pooled sample using distribution volume ratios (DVR) standardized (z-scored) by region from 42 bilateral regions of interest (ROI). RESULTS: Parallel analysis determined three significant PCs explaining 70.2% of the total variance. PC1 was characterized by positive loadings with similar contributions across the majority of ROIs. PC2 was characterized by positive and negative loadings with strongest contributions from subcortical and parietooccipital cortical regions, respectively, while PC3 was characterized by positive and negative loadings with strongest contributions from rostral and caudal cortical regions, respectively. Within the AD group, PC1 subject scores were positively correlated with performance across all cognitive domains (Pearson r = 0.24-0.40, P = 0.06-0.006), PC2 subject scores were inversely correlated with age (Pearson r = -0.45, P = 0.002) and PC3 subject scores were significantly correlated with CDR-sb (Pearson r = 0.46, P = 0.04). No significant correlations were observed between cognitive performance and PC subject scores in CN participants. CONCLUSIONS: This data-driven approach defined specific spatial patterns of synaptic density correlated with unique participant characteristics within the AD group. Our findings reinforce synaptic density as a robust biomarker of disease presence and severity in the early stages of AD.

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YNIMG Journal 2021 Journal Article

Partial volume correction analysis for 11C-UCB-J PET studies of Alzheimer's disease

Yihuan Lu
Takuya Toyonaga
Mika Naganawa
Jean-Dominique Gallezot
Ming-Kai Chen
Adam P. Mecca
Christopher H. van Dyck
Richard E. Carson

PURPOSE: C-UCB-J PET imaging, targeting synaptic vesicle glycoprotein 2A (SV2A), has been shown to be a useful indicator of synaptic density in Alzheimer's disease (AD). For SV2A imaging, a decrease in apparent tracer uptake is often due to the combination of gray-matter (GM) atrophy and SV2A decrease in the remaining tissue. Our aim is to reveal the true SV2A change by performing partial volume correction (PVC). METHODS: (centrum semiovale as reference region), and tissue volume were compared. RESULTS: group differences: uncorrected: 20%, 27%, 17%; MG: 18%, 22%, 14%; IY: 22%, 28%, 17%). The group difference in hippocampal volume (10%) was substantially smaller than any PET measures. MG increased GM binding values to a greater extent than IY due to differences in algorithm assumptions. CONCLUSION: C-UCB-J, the less stringent assumptions of IY support its use as a PVC algorithm over MG.

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YNIMG Journal 2006 Journal Article

An extended simplified reference tissue model for the quantification of dynamic PET with amphetamine challenge

Yun Zhou
Ming-Kai Chen
Christopher J. Endres
Weiguo Ye
James R. Brašić
Mohab Alexander
Andrew H. Crabb
Tomás R. Guilarte

Background: Equilibrium analysis to quantify dynamic positron emission tomography (PET) with bolus followed by continuous tracer infusion and acute amphetamine challenge assumes that all tissue kinetics attain steady states during pre- and post-challenge phases. Violations of this assumption may result in unreliable estimation of the amphetamine-induced percent change in the binding potential (ΔBP%). Method: We derived an extended simplified reference tissue model (ESRTM) for modeling tracer kinetics in the pre- and post-challenge phases. Ninety-minute [11C]raclopride PET studies with bolus injection followed by continuous tracer infusion were performed on 18 monkeys and 2 baboons. Forty minutes after the bolus injection, a single acute intravenous amphetamine administration was given of 2. 0 mg/kg to monkeys and of 0. 05, 0. 1, 0. 5, and 1. 5 mg/kg to baboons. Computer simulations further evaluated and characterized the ESRTM. Results: In monkey studies, the ΔBP% estimated by the ESRTM was 32±11, whereas, the ΔBP% obtained using the equilibrium methods was 32% to 81% lower. In baboon studies, the ΔBP% values estimated with the ESRTM showed a linear relationship between the ΔBP% and the natural logarithm of amphetamine dose (R 2 =0. 96), where the ΔBP%=10. 67Ln(dose)+33. 79 (0. 05≤dose in mg/kg≤1. 5). At 1. 5 mg/kg amphetamine, the ΔBP% estimates from equilibrium methods were 18% to 40% lower than those estimated by the ESRTM. Results showed that the nonsteady state of tracer kinetics produced an underestimation of the ΔBP% from the equilibrium analysis. The accuracy of the ΔBP% estimates from the equilibrium analysis was significantly improved by the ESRTM. The ΔBP% estimated by the ESRTM in the study was consistent with that from previous [11C]raclopride PET with amphetamine challenge. Conclusion: In conclusion, the ESRTM is a robust kinetic modeling approach and is proposed for the quantification of dynamic PET with acute amphetamine stimulation.

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