A disease-specific metabolic imaging marker for diagnosis and progression evaluation of semantic variant primary progressive aphasia
Jiaying Lu
PET Center, Huashan Hospital, Fudan University, Shanghai, China
Contribution: Formal analysis (lead), Investigation (equal), Methodology (lead), Writing - original draft (lead)
Search for more papers by this authorLin Huang
Department of Gerontology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China
Contribution: Data curation (lead), Investigation (equal), Writing - original draft (lead)
Search for more papers by this authorYingru Lv
Department of Radiology, Huashan Hospital, Fudan University, Shanghai, China
Contribution: Data curation (supporting), Investigation (supporting), Writing - review & editing (equal)
Search for more papers by this authorShichun Peng
Center for Neurosciences, Institute of Molecular Medicine, Feinstein Institutes for Medical Research, Northwell Health, Manhasset, New York, USA
Contribution: Methodology (equal), Software (equal), Writing - review & editing (equal)
Search for more papers by this authorQian Xu
Department of Nuclear Medicine, Huashan Hospital, Fudan University, Shanghai, China
Contribution: Formal analysis (supporting), Investigation (equal), Writing - review & editing (equal)
Search for more papers by this authorLing Li
PET Center, Huashan Hospital, Fudan University, Shanghai, China
Contribution: Formal analysis (supporting), Investigation (equal), Methodology (supporting), Writing - review & editing (equal)
Search for more papers by this authorJingjie Ge
PET Center, Huashan Hospital, Fudan University, Shanghai, China
Contribution: Funding acquisition (equal), Investigation (equal), Methodology (supporting), Writing - review & editing (equal)
Search for more papers by this authorHuiwei Zhang
PET Center, Huashan Hospital, Fudan University, Shanghai, China
Contribution: Data curation (equal), Formal analysis (supporting), Investigation (equal), Writing - review & editing (equal)
Search for more papers by this authorYihui Guan
PET Center, Huashan Hospital, Fudan University, Shanghai, China
Contribution: Project administration (supporting), Writing - review & editing (supporting)
Search for more papers by this authorQianhua Zhao
Department of Neurology, Huashan Hospital, Fudan University, Shanghai, China
Contribution: Conceptualization (supporting), Investigation (supporting), Writing - review & editing (supporting)
Search for more papers by this authorQihao Guo
Department of Gerontology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China
Contribution: Conceptualization (equal), Funding acquisition (equal), Project administration (equal), Writing - review & editing (equal)
Search for more papers by this authorCorresponding Author
Keliang Chen
Department of Neurology, Huashan Hospital, Fudan University, Shanghai, China
Correspondence
Ping Wu, PET Center, Huashan Hospital, Fudan University, No. 518 East Wuzhong Road, Shanghai 200035, China.
Email: [email protected]
Keliang Chen, Department of Neurology, Huashan Hospital, Fudan University, No. 12 Middle Wulumuqi Road, Shanghai 200040, China.
Email: [email protected]
Contribution: Conceptualization (equal), Data curation (equal), Project administration (equal), Supervision (equal), Writing - review & editing (lead)
Search for more papers by this authorCorresponding Author
Ping Wu
PET Center, Huashan Hospital, Fudan University, Shanghai, China
Correspondence
Ping Wu, PET Center, Huashan Hospital, Fudan University, No. 518 East Wuzhong Road, Shanghai 200035, China.
Email: [email protected]
Keliang Chen, Department of Neurology, Huashan Hospital, Fudan University, No. 12 Middle Wulumuqi Road, Shanghai 200040, China.
Email: [email protected]
Contribution: Conceptualization (equal), Funding acquisition (equal), Project administration (equal), Supervision (lead), Writing - review & editing (lead)
Search for more papers by this authorYilong Ma
Center for Neurosciences, Institute of Molecular Medicine, Feinstein Institutes for Medical Research, Northwell Health, Manhasset, New York, USA
Contribution: Methodology (equal), Software (equal), Writing - review & editing (equal)
Search for more papers by this authorChuantao Zuo
PET Center, Huashan Hospital, Fudan University, Shanghai, China
National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai, China
Human Phenome Institute, Fudan University, Shanghai, China
Institute of Functional and Molecular Medicine Imaging, Fudan University, Shanghai, China
Contribution: Conceptualization (equal), Funding acquisition (supporting), Project administration (equal), Supervision (equal), Writing - review & editing (equal)
Search for more papers by this authorJiaying Lu
PET Center, Huashan Hospital, Fudan University, Shanghai, China
Contribution: Formal analysis (lead), Investigation (equal), Methodology (lead), Writing - original draft (lead)
Search for more papers by this authorLin Huang
Department of Gerontology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China
Contribution: Data curation (lead), Investigation (equal), Writing - original draft (lead)
Search for more papers by this authorYingru Lv
Department of Radiology, Huashan Hospital, Fudan University, Shanghai, China
Contribution: Data curation (supporting), Investigation (supporting), Writing - review & editing (equal)
Search for more papers by this authorShichun Peng
Center for Neurosciences, Institute of Molecular Medicine, Feinstein Institutes for Medical Research, Northwell Health, Manhasset, New York, USA
Contribution: Methodology (equal), Software (equal), Writing - review & editing (equal)
Search for more papers by this authorQian Xu
Department of Nuclear Medicine, Huashan Hospital, Fudan University, Shanghai, China
Contribution: Formal analysis (supporting), Investigation (equal), Writing - review & editing (equal)
Search for more papers by this authorLing Li
PET Center, Huashan Hospital, Fudan University, Shanghai, China
Contribution: Formal analysis (supporting), Investigation (equal), Methodology (supporting), Writing - review & editing (equal)
Search for more papers by this authorJingjie Ge
PET Center, Huashan Hospital, Fudan University, Shanghai, China
Contribution: Funding acquisition (equal), Investigation (equal), Methodology (supporting), Writing - review & editing (equal)
Search for more papers by this authorHuiwei Zhang
PET Center, Huashan Hospital, Fudan University, Shanghai, China
Contribution: Data curation (equal), Formal analysis (supporting), Investigation (equal), Writing - review & editing (equal)
Search for more papers by this authorYihui Guan
PET Center, Huashan Hospital, Fudan University, Shanghai, China
Contribution: Project administration (supporting), Writing - review & editing (supporting)
Search for more papers by this authorQianhua Zhao
Department of Neurology, Huashan Hospital, Fudan University, Shanghai, China
Contribution: Conceptualization (supporting), Investigation (supporting), Writing - review & editing (supporting)
Search for more papers by this authorQihao Guo
Department of Gerontology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China
Contribution: Conceptualization (equal), Funding acquisition (equal), Project administration (equal), Writing - review & editing (equal)
Search for more papers by this authorCorresponding Author
Keliang Chen
Department of Neurology, Huashan Hospital, Fudan University, Shanghai, China
Correspondence
Ping Wu, PET Center, Huashan Hospital, Fudan University, No. 518 East Wuzhong Road, Shanghai 200035, China.
Email: [email protected]
Keliang Chen, Department of Neurology, Huashan Hospital, Fudan University, No. 12 Middle Wulumuqi Road, Shanghai 200040, China.
Email: [email protected]
Contribution: Conceptualization (equal), Data curation (equal), Project administration (equal), Supervision (equal), Writing - review & editing (lead)
Search for more papers by this authorCorresponding Author
Ping Wu
PET Center, Huashan Hospital, Fudan University, Shanghai, China
Correspondence
Ping Wu, PET Center, Huashan Hospital, Fudan University, No. 518 East Wuzhong Road, Shanghai 200035, China.
Email: [email protected]
Keliang Chen, Department of Neurology, Huashan Hospital, Fudan University, No. 12 Middle Wulumuqi Road, Shanghai 200040, China.
Email: [email protected]
Contribution: Conceptualization (equal), Funding acquisition (equal), Project administration (equal), Supervision (lead), Writing - review & editing (lead)
Search for more papers by this authorYilong Ma
Center for Neurosciences, Institute of Molecular Medicine, Feinstein Institutes for Medical Research, Northwell Health, Manhasset, New York, USA
Contribution: Methodology (equal), Software (equal), Writing - review & editing (equal)
Search for more papers by this authorChuantao Zuo
PET Center, Huashan Hospital, Fudan University, Shanghai, China
National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai, China
Human Phenome Institute, Fudan University, Shanghai, China
Institute of Functional and Molecular Medicine Imaging, Fudan University, Shanghai, China
Contribution: Conceptualization (equal), Funding acquisition (supporting), Project administration (equal), Supervision (equal), Writing - review & editing (equal)
Search for more papers by this authorJiaying Lu and Lin Huang contributed equally to this work.
Keliang Chen and Ping Wu jointly supervised the work.
Abstract
Background and purpose
The diagnosis and monitoring of semantic variant primary progressive aphasia (sv-PPA) are clinically challenging. We aimed to establish a distinctive metabolic pattern in sv-PPA for diagnosis and severity evaluation.
Methods
Fifteen sv-PPA patients and 15 controls were enrolled to identify sv-PPA-related pattern (sv-PPARP) by principal component analysis of 18F-fluorodeoxyglucose positron emission tomography. Eighteen Alzheimer disease dementia (AD) and 14 behavioral variant frontotemporal dementia (bv-FTD) patients were enrolled to test the discriminatory power. Correspondingly, regional metabolic activities extracted from the voxelwise analysis were evaluated for the discriminatory power.
Results
The sv-PPARP was characterized as decreased metabolic activity mainly in the bilateral temporal lobe (left predominance), middle orbitofrontal gyrus, left hippocampus/parahippocampus gyrus, fusiform gyrus, insula, inferior orbitofrontal gyrus, and striatum, with increased activity in the bilateral lingual gyrus, cuneus, calcarine gyrus, and right precentral and postcentral gyrus. The pattern expression had significant discriminatory power (area under the curve [AUC] = 0.98, sensitivity = 100%, specificity = 94.4%) in distinguishing sv-PPA from AD, and the asymmetry index offered complementary discriminatory power (AUC = 0.91, sensitivity = 86.7%, specificity = 92.9%) in distinguishing sv-PPA from bv-FTD. In sv-PPA patients, the pattern expression correlated with Boston Naming Test scores at baseline and showed significant increase in the subset of patients with follow-up. The voxelwise analysis showed similar topography, and the regional metabolic activities had equivalent or better discriminatory power and clinical correlations with Boston Naming Test scores. The ability to reflect disease progression in longitudinal follow-up seemed to be inferior to the pattern expression.
Conclusions
The sv-PPARP might serve as an objective biomarker for diagnosis and progression evaluation.
CONFLICT OF INTEREST
The authors declare no conflicts of interest.
Open Research
DATA AVAILABILITY STATEMENT
Data that support the findings of this study are available from the corresponding authors upon reasonable request.
Supporting Information
| Filename | Description |
|---|---|
| ene14919-sup-0001-AppS1.docxWord document, 11.6 MB | App S1 |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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