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Published in: European Journal of Nuclear Medicine and Molecular Imaging 8/2022

Open Access 19-05-2022 | Positron Emission Tomography | Original Article

Decoding the dopamine transporter imaging for the differential diagnosis of parkinsonism using deep learning

Authors: Yu Zhao, Ping Wu, Jianjun Wu, Matthias Brendel, Jiaying Lu, Jingjie Ge, Chunmeng Tang, Jimin Hong, Qian Xu, Fengtao Liu, Yimin Sun, Zizhao Ju, Huamei Lin, Yihui Guan, Claudio Bassetti, Markus Schwaiger, Sung-Cheng Huang, Axel Rominger, Jian Wang, Chuantao Zuo, Kuangyu Shi

Published in: European Journal of Nuclear Medicine and Molecular Imaging | Issue 8/2022

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Abstract

Purpose

This work attempts to decode the discriminative information in dopamine transporter (DAT) imaging using deep learning for the differential diagnosis of parkinsonism.

Methods

This study involved 1017 subjects who underwent DAT PET imaging ([11C]CFT) including 43 healthy subjects and 974 parkinsonian patients with idiopathic Parkinson’s disease (IPD), multiple system atrophy (MSA) or progressive supranuclear palsy (PSP). We developed a 3D deep convolutional neural network to learn distinguishable DAT features for the differential diagnosis of parkinsonism. A full-gradient saliency map approach was employed to investigate the functional basis related to the decision mechanism of the network. Furthermore, deep-learning-guided radiomics features and quantitative analysis were compared with their conventional counterparts to further interpret the performance of deep learning.

Results

The proposed network achieved area under the curve of 0.953 (sensitivity 87.7%, specificity 93.2%), 0.948 (sensitivity 93.7%, specificity 97.5%), and 0.900 (sensitivity 81.5%, specificity 93.7%) in the cross-validation, together with sensitivity of 90.7%, 84.1%, 78.6% and specificity of 88.4%, 97.5% 93.3% in the blind test for the differential diagnosis of IPD, MSA and PSP, respectively. The saliency map demonstrated the most contributed areas determining the diagnosis located at parkinsonism-related regions, e.g., putamen, caudate and midbrain. The deep-learning-guided binding ratios showed significant differences among IPD, MSA and PSP groups (P < 0.001), while the conventional putamen and caudate binding ratios had no significant difference between IPD and MSA (P = 0.24 and P = 0.30). Furthermore, compared to conventional radiomics features, there existed average above 78.1% more deep-learning-guided radiomics features that had significant differences among IPD, MSA and PSP.

Conclusion

This study suggested the developed deep neural network can decode in-depth information from DAT and showed potential to assist the differential diagnosis of parkinsonism. The functional regions supporting the diagnosis decision were generally consistent with known parkinsonian pathology but provided more specific guidance for feature selection and quantitative analysis.
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Literature
1.
go back to reference Hughes AJ, Daniel SE, Ben-Shlomo Y, Lees AJ. The accuracy of diagnosis of parkinsonian syndromes in a specialist movement disorder service. Brain. 2002;125:861–70.CrossRef Hughes AJ, Daniel SE, Ben-Shlomo Y, Lees AJ. The accuracy of diagnosis of parkinsonian syndromes in a specialist movement disorder service. Brain. 2002;125:861–70.CrossRef
2.
go back to reference de la Fuente-Fernández R. Role of DaTSCAN and clinical diagnosis in Parkinson disease. Neurology. 2012;78:696–701.CrossRef de la Fuente-Fernández R. Role of DaTSCAN and clinical diagnosis in Parkinson disease. Neurology. 2012;78:696–701.CrossRef
3.
go back to reference Albert NL, Unterrainer M, Diemling M, Xiong G, Bartenstein P, Koch W, et al. Implementation of the European multicentre database of healthy controls for [123 I] FP-CIT SPECT increases diagnostic accuracy in patients with clinically uncertain parkinsonian syndromes. Eur J Nucl Med Mol Imaging. 2016;43:1315–22.CrossRef Albert NL, Unterrainer M, Diemling M, Xiong G, Bartenstein P, Koch W, et al. Implementation of the European multicentre database of healthy controls for [123 I] FP-CIT SPECT increases diagnostic accuracy in patients with clinically uncertain parkinsonian syndromes. Eur J Nucl Med Mol Imaging. 2016;43:1315–22.CrossRef
4.
go back to reference Isaias IU, Marotta G, Pezzoli G, Sabri O, Hesse S. [123I] FP-CIT SPECT in atypical degenerative parkinsonism. Imaging in Medicine. 2012;4:411–21.CrossRef Isaias IU, Marotta G, Pezzoli G, Sabri O, Hesse S. [123I] FP-CIT SPECT in atypical degenerative parkinsonism. Imaging in Medicine. 2012;4:411–21.CrossRef
5.
go back to reference Meyer PT, Hellwig S, Amtage F. Differential Diagnostics of Neurodegenerative Parkinsonian Syndromes with Nuclear Medicine Procedures. Der Nuklearmediziner. 2012;35:109–23.CrossRef Meyer PT, Hellwig S, Amtage F. Differential Diagnostics of Neurodegenerative Parkinsonian Syndromes with Nuclear Medicine Procedures. Der Nuklearmediziner. 2012;35:109–23.CrossRef
6.
go back to reference Buchert R, Buhmann C, Apostolova I, Meyer PT, Gallinat JJDÄI. Nuclear Imaging in the Diagnosis of Clinically Uncertain Parkinsonian Syndromes. 2019;116:747. Buchert R, Buhmann C, Apostolova I, Meyer PT, Gallinat JJDÄI. Nuclear Imaging in the Diagnosis of Clinically Uncertain Parkinsonian Syndromes. 2019;116:747.
8.
go back to reference Norgeot B, Glicksberg BS, Butte AJ. A call for deep-learning healthcare. Nat Med. 2019;25:14.CrossRef Norgeot B, Glicksberg BS, Butte AJ. A call for deep-learning healthcare. Nat Med. 2019;25:14.CrossRef
9.
go back to reference Xu M, Wang Z, Zhang H, Pantazis D, Wang H, Li Q. A new Graph Gaussian embedding method for analyzing the effects of cognitive training. PLoS Comput Biol. 2020;16:e1008186.CrossRef Xu M, Wang Z, Zhang H, Pantazis D, Wang H, Li Q. A new Graph Gaussian embedding method for analyzing the effects of cognitive training. PLoS Comput Biol. 2020;16:e1008186.CrossRef
10.
go back to reference Qiu S, Joshi PS, Miller MI, Xue C, Zhou X, Karjadi C, et al. Development and validation of an interpretable deep learning framework for Alzheimer’s disease classification. Brain. 2020;143:1920–33.CrossRef Qiu S, Joshi PS, Miller MI, Xue C, Zhou X, Karjadi C, et al. Development and validation of an interpretable deep learning framework for Alzheimer’s disease classification. Brain. 2020;143:1920–33.CrossRef
11.
go back to reference Bashyam VM, Erus G, Doshi J, Habes M, Nasrallah IM, Truelove-Hill M, et al. MRI signatures of brain age and disease over the lifespan based on a deep brain network and 14 468 individuals worldwide. Brain. 2020;143:2312–24.CrossRef Bashyam VM, Erus G, Doshi J, Habes M, Nasrallah IM, Truelove-Hill M, et al. MRI signatures of brain age and disease over the lifespan based on a deep brain network and 14 468 individuals worldwide. Brain. 2020;143:2312–24.CrossRef
12.
go back to reference Tang J, Yang B, Adams MP, Shenkov NN, Klyuzhin IS, Fotouhi S, et al. Artificial Neural Network-Based Prediction of Outcome in Parkinson’s Disease Patients Using DaTscan SPECT Imaging Features. Mol Imag Biol. 2019;21:1165–73.CrossRef Tang J, Yang B, Adams MP, Shenkov NN, Klyuzhin IS, Fotouhi S, et al. Artificial Neural Network-Based Prediction of Outcome in Parkinson’s Disease Patients Using DaTscan SPECT Imaging Features. Mol Imag Biol. 2019;21:1165–73.CrossRef
13.
go back to reference Parekh VS, Jacobs MA. Deep learning and radiomics in precision medicine. Expert Rev Precis Med Drug Dev. 2019;4:59–72.CrossRef Parekh VS, Jacobs MA. Deep learning and radiomics in precision medicine. Expert Rev Precis Med Drug Dev. 2019;4:59–72.CrossRef
14.
go back to reference Hosny A, Parmar C, Coroller TP, Grossmann P, Zeleznik R, Kumar A, et al. Deep learning for lung cancer prognostication: A retrospective multi-cohort radiomics study. PLoS Med. 2018;15:e1002711.CrossRef Hosny A, Parmar C, Coroller TP, Grossmann P, Zeleznik R, Kumar A, et al. Deep learning for lung cancer prognostication: A retrospective multi-cohort radiomics study. PLoS Med. 2018;15:e1002711.CrossRef
15.
go back to reference Nazari M, Kluge A, Apostolova I, Klutmann S, Kimiaei S, Schroeder M, et al. Explainable AI to improve acceptance of convolutional neural networks for automatic classification of dopamine transporter SPECT in the diagnosis of clinically uncertain parkinsonian syndromes. Eur J Nucl Med Mol Imaging. 2022;49:1176–86. https://doi.org/10.1007/s00259-021-05569-9. Nazari M, Kluge A, Apostolova I, Klutmann S, Kimiaei S, Schroeder M, et al. Explainable AI to improve acceptance of convolutional neural networks for automatic classification of dopamine transporter SPECT in the diagnosis of clinically uncertain parkinsonian syndromes. Eur J Nucl Med Mol Imaging. 2022;49:1176–86. https://​doi.​org/​10.​1007/​s00259-021-05569-9.
16.
go back to reference Choi H, Ha S, Im HJ, Paek SH, Lee DS. Refining diagnosis of Parkinson’s disease with deep learning-based interpretation of dopamine transporter imaging. NeuroImage Clin. 2017;16:586–94.CrossRef Choi H, Ha S, Im HJ, Paek SH, Lee DS. Refining diagnosis of Parkinson’s disease with deep learning-based interpretation of dopamine transporter imaging. NeuroImage Clin. 2017;16:586–94.CrossRef
17.
go back to reference Wenzel M, Milletari F, Krüger J, Lange C, Schenk M, Apostolova I, et al. Automatic classification of dopamine transporter SPECT: deep convolutional neural networks can be trained to be robust with respect to variable image characteristics. Eur J Nucl Med Mol Imaging. 2019;46:2800–11.CrossRef Wenzel M, Milletari F, Krüger J, Lange C, Schenk M, Apostolova I, et al. Automatic classification of dopamine transporter SPECT: deep convolutional neural networks can be trained to be robust with respect to variable image characteristics. Eur J Nucl Med Mol Imaging. 2019;46:2800–11.CrossRef
18.
go back to reference Nazari M, Kluge A, Apostolova I, Klutmann S, Kimiaei S, Schroeder M, et al. Data-driven identification of diagnostically useful extrastriatal signal in dopamine transporter SPECT using explainable AI. Sci Rep. 2021;11:1–13.CrossRef Nazari M, Kluge A, Apostolova I, Klutmann S, Kimiaei S, Schroeder M, et al. Data-driven identification of diagnostically useful extrastriatal signal in dopamine transporter SPECT using explainable AI. Sci Rep. 2021;11:1–13.CrossRef
19.
go back to reference Suh M, Im JH, Choi H, Kim HJ, Cheon GJ, Jeon B. Unsupervised clustering of dopamine transporter PET imaging discovers heterogeneity of parkinsonism. Hum Brain Mapp. 2020;41:4744–52.CrossRef Suh M, Im JH, Choi H, Kim HJ, Cheon GJ, Jeon B. Unsupervised clustering of dopamine transporter PET imaging discovers heterogeneity of parkinsonism. Hum Brain Mapp. 2020;41:4744–52.CrossRef
21.
go back to reference Gilman S, Wenning GK, Low PA, Brooks DJ, Mathias CJ, Trojanowski JQ, et al. Second consensus statement on the diagnosis of multiple system atrophy. Neurology. 2008;71:670–6.CrossRef Gilman S, Wenning GK, Low PA, Brooks DJ, Mathias CJ, Trojanowski JQ, et al. Second consensus statement on the diagnosis of multiple system atrophy. Neurology. 2008;71:670–6.CrossRef
22.
go back to reference Höglinger GU, Respondek G, Stamelou M, Kurz C, Josephs KA, Lang AE, et al. Clinical diagnosis of progressive supranuclear palsy: the movement disorder society criteria. Mov Disord. 2017;32:853–64.CrossRef Höglinger GU, Respondek G, Stamelou M, Kurz C, Josephs KA, Lang AE, et al. Clinical diagnosis of progressive supranuclear palsy: the movement disorder society criteria. Mov Disord. 2017;32:853–64.CrossRef
23.
go back to reference Postuma RB, Berg D, Stern M, Poewe W, Olanow CW, Oertel W, et al. MDS clinical diagnostic criteria for Parkinson’s disease. Mov Disord. 2015;30:1591–601.CrossRef Postuma RB, Berg D, Stern M, Poewe W, Olanow CW, Oertel W, et al. MDS clinical diagnostic criteria for Parkinson’s disease. Mov Disord. 2015;30:1591–601.CrossRef
24.
go back to reference Huang Z, Jiang C, Li L, Xu Q, Ge J, Li M, et al. Correlations between dopaminergic dysfunction and abnormal metabolic network activity in REM sleep behavior disorder. J Cereb Blood Flow Metab. 2020;40:552–62.CrossRef Huang Z, Jiang C, Li L, Xu Q, Ge J, Li M, et al. Correlations between dopaminergic dysfunction and abnormal metabolic network activity in REM sleep behavior disorder. J Cereb Blood Flow Metab. 2020;40:552–62.CrossRef
25.
go back to reference Bu LL, Liu FT, Jiang CF, Guo SS, Yu H, Zuo CT, et al. Patterns of dopamine transporter imaging in subtypes of multiple system atrophy. Acta Neurol Scand. 2018;138:170–6.CrossRef Bu LL, Liu FT, Jiang CF, Guo SS, Yu H, Zuo CT, et al. Patterns of dopamine transporter imaging in subtypes of multiple system atrophy. Acta Neurol Scand. 2018;138:170–6.CrossRef
27.
go back to reference Van Griethuysen JJ, Fedorov A, Parmar C, Hosny A, Aucoin N, Narayan V, et al. Computational radiomics system to decode the radiographic phenotype. Can Res. 2017;77:e104–7.CrossRef Van Griethuysen JJ, Fedorov A, Parmar C, Hosny A, Aucoin N, Narayan V, et al. Computational radiomics system to decode the radiographic phenotype. Can Res. 2017;77:e104–7.CrossRef
29.
go back to reference Pirker W, Asenbaum S, Bencsits G, Prayer D, Gerschlager W, Deecke L, et al. [123I] β-CIT SPECT in multiple system atrophy, progressive supranuclear palsy, and corticobasal degeneration. Movement disorders: official journal of the Movement Disorder Society. 2000;15:1158–67.CrossRef Pirker W, Asenbaum S, Bencsits G, Prayer D, Gerschlager W, Deecke L, et al. [123I] β-CIT SPECT in multiple system atrophy, progressive supranuclear palsy, and corticobasal degeneration. Movement disorders: official journal of the Movement Disorder Society. 2000;15:1158–67.CrossRef
30.
go back to reference Varrone A, Marek KL, Jennings D, Innis RB, Seibyl JP. [123I] β-CIT SPECT imaging demonstrates reduced density of striatal dopamine transporters in Parkinson’s disease and multiple system atrophy. Movement disorders: official journal of the Movement Disorder Society. 2001;16:1023–32.CrossRef Varrone A, Marek KL, Jennings D, Innis RB, Seibyl JP. [123I] β-CIT SPECT imaging demonstrates reduced density of striatal dopamine transporters in Parkinson’s disease and multiple system atrophy. Movement disorders: official journal of the Movement Disorder Society. 2001;16:1023–32.CrossRef
31.
go back to reference Nurmi E, Ruottinen HM, Kaasinen V, Bergman J, Haaparanta M, Solin O, et al. Progression in Parkinson’s disease: a positron emission tomography study with a dopamine transporter ligand [18F] CFT. Annals of Neurology: Official Journal of the American Neurological Association and the Child Neurology Society. 2000;47:804–8.CrossRef Nurmi E, Ruottinen HM, Kaasinen V, Bergman J, Haaparanta M, Solin O, et al. Progression in Parkinson’s disease: a positron emission tomography study with a dopamine transporter ligand [18F] CFT. Annals of Neurology: Official Journal of the American Neurological Association and the Child Neurology Society. 2000;47:804–8.CrossRef
32.
go back to reference Nurmi E, Ruottinen HM, Bergman J, Haaparanta M, Solin O, Sonninen P, et al. Rate of progression in Parkinson’s disease: a 6-[18F] fluoro-L-dopa PET study. Movement disorders: official journal of the Movement Disorder Society. 2001;16:608–15.CrossRef Nurmi E, Ruottinen HM, Bergman J, Haaparanta M, Solin O, Sonninen P, et al. Rate of progression in Parkinson’s disease: a 6-[18F] fluoro-L-dopa PET study. Movement disorders: official journal of the Movement Disorder Society. 2001;16:608–15.CrossRef
33.
go back to reference Liu F-T, Ge J-J, Wu J-J, Wu P, Ma Y, Zuo C-T, et al. Clinical, dopaminergic, and metabolic correlations in Parkinson disease: a dual-tracer PET study. Clin Nucl Med. 2018;43:562–71.CrossRef Liu F-T, Ge J-J, Wu J-J, Wu P, Ma Y, Zuo C-T, et al. Clinical, dopaminergic, and metabolic correlations in Parkinson disease: a dual-tracer PET study. Clin Nucl Med. 2018;43:562–71.CrossRef
34.
go back to reference Scherfler C, Seppi K, Donnemiller E, Goebel G, Brenneis C, Virgolini I, et al. Voxel-wise analysis of [123I] β-CIT SPECT differentiates the Parkinson variant of multiple system atrophy from idiopathic Parkinson’s disease. Brain. 2005;128:1605–12.CrossRef Scherfler C, Seppi K, Donnemiller E, Goebel G, Brenneis C, Virgolini I, et al. Voxel-wise analysis of [123I] β-CIT SPECT differentiates the Parkinson variant of multiple system atrophy from idiopathic Parkinson’s disease. Brain. 2005;128:1605–12.CrossRef
35.
go back to reference Poulin J-F, Gaertner Z, Moreno-Ramos OA, Awatramani R. Classification of midbrain dopamine neurons using single-cell gene expression profiling approaches. Trends Neurosci. 2020;43:155–69.CrossRef Poulin J-F, Gaertner Z, Moreno-Ramos OA, Awatramani R. Classification of midbrain dopamine neurons using single-cell gene expression profiling approaches. Trends Neurosci. 2020;43:155–69.CrossRef
36.
go back to reference Roselli F, Pisciotta NM, Pennelli M, Aniello MS, Gigante A, De Caro MF, et al. Midbrain SERT in degenerative parkinsonisms: a 123I-FP-CIT SPECT study. Mov Disord. 2010;25:1853–9.CrossRef Roselli F, Pisciotta NM, Pennelli M, Aniello MS, Gigante A, De Caro MF, et al. Midbrain SERT in degenerative parkinsonisms: a 123I-FP-CIT SPECT study. Mov Disord. 2010;25:1853–9.CrossRef
37.
go back to reference Oh M, Kim JS, Kim JY, Shin K-H, Park SH, Kim HO, et al. Subregional patterns of preferential striatal dopamine transporter loss differ in Parkinson disease, progressive supranuclear palsy, and multiple-system atrophy. J Nucl Med. 2012;53:399–406.CrossRef Oh M, Kim JS, Kim JY, Shin K-H, Park SH, Kim HO, et al. Subregional patterns of preferential striatal dopamine transporter loss differ in Parkinson disease, progressive supranuclear palsy, and multiple-system atrophy. J Nucl Med. 2012;53:399–406.CrossRef
38.
go back to reference Pirker W, Djamshidian S, Asenbaum S, Gerschlager W, Tribl G, Hoffmann M, et al. Progression of dopaminergic degeneration in Parkinson’s disease and atypical parkinsonism: A longitudinal β-CIT SPECT study. Mov Disord. 2002;17:45–53.CrossRef Pirker W, Djamshidian S, Asenbaum S, Gerschlager W, Tribl G, Hoffmann M, et al. Progression of dopaminergic degeneration in Parkinson’s disease and atypical parkinsonism: A longitudinal β-CIT SPECT study. Mov Disord. 2002;17:45–53.CrossRef
39.
go back to reference Chen RJ, Lu MY, Wang J, Williamson DFK, Rodig SJ, Lindeman NI, et al. Pathomic fusion: an integrated framework for fusing histopathology and genomic features for cancer diagnosis and prognosis. IEEE Trans Med Imaging. Institute of Electrical and Electronics Engineers (IEEE) 2020;1–1. https://doi.org/10.1109/TMI.2020.3021387. Chen RJ, Lu MY, Wang J, Williamson DFK, Rodig SJ, Lindeman NI, et al. Pathomic fusion: an integrated framework for fusing histopathology and genomic features for cancer diagnosis and prognosis. IEEE Trans Med Imaging. Institute of Electrical and Electronics Engineers (IEEE) 2020;1–1. https://​doi.​org/​10.​1109/​TMI.​2020.​3021387.
40.
go back to reference Ganin Y, Ustinova E, Ajakan H, Germain P, Larochelle H, Laviolette F, et al. Domain-adversarial training of neural networks. J Mach Learn Res. 2016;17:2096–130. Ganin Y, Ustinova E, Ajakan H, Germain P, Larochelle H, Laviolette F, et al. Domain-adversarial training of neural networks. J Mach Learn Res. 2016;17:2096–130.
Metadata
Title
Decoding the dopamine transporter imaging for the differential diagnosis of parkinsonism using deep learning
Authors
Yu Zhao
Ping Wu
Jianjun Wu
Matthias Brendel
Jiaying Lu
Jingjie Ge
Chunmeng Tang
Jimin Hong
Qian Xu
Fengtao Liu
Yimin Sun
Zizhao Ju
Huamei Lin
Yihui Guan
Claudio Bassetti
Markus Schwaiger
Sung-Cheng Huang
Axel Rominger
Jian Wang
Chuantao Zuo
Kuangyu Shi
Publication date
19-05-2022
Publisher
Springer Berlin Heidelberg
Published in
European Journal of Nuclear Medicine and Molecular Imaging / Issue 8/2022
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI
https://doi.org/10.1007/s00259-022-05804-x

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