Neurodegenerative Research Programme

The Neurodegenerative Research Programme uses advanced quantitative MRI techniques to understand pathophysiological changes in the brain and improve clinical diagnosis.

The aim is to assess the utility of multimodal MR imaging in evaluating the brain in patients with various neurological disorders and to identify potential radiological biomarkers.

The program focuses on neuroimaging of the Parkinsonism, normal pressure hydrocephalus and dementia. The team utilises radiographic markers and multimodal MRI imaging to differentiate different types of parkinsonism and dementia, localize and characterise brain atrophy, midbrain and white matter changes, and quantitate microstructural and functional connectivity changes in the evaluation of clinical parkinsonism, gait and cognitive dysfunction. More information is available at the SGH MRI Research Lab.

Neuromelanin-sensitive MRI (left), QSM (middle) and SMWI (right) in healthy subject (top) and PD patient (bottom). Neuromelanin hyperintensity was reduced while there was an increase of iron deposition in QSM and elevated SMWI signals in PD patient. Nigrosome-1 (yellow arrow) was clearly seen in healthy subject but was lost in PD patient.

Axial FLAIR, sagittal 3D SPACE and coronal MPRAGE (extreme columns) and axial color FA (mid panels) images of a patient with normal pressure hydrocephalus (left) demonstrating an enlarged Evans’ index >0.3, dynamic high velocity flow void in the patent cerebral aqueduct and an acute callosal angle. The splenial angle, a novel angular index for evaluation of normal pressure hydrocephalus, is narrowed on the axial color FA map when compared to that in the healthy elderly (right).

Contact

Please contact Prof Chan Ling Ling at chan.ling.ling@singhealth.com.sg for more information.

Publications:

1. Lee S, Chen R, Kumar S, Lee W, Li H, Tan LCS, Tan EK, Keong NCH, Chan LL. Splenial angle on axial T1 and fluid-attenuated inversion-recovery MRI images and idiopathic normal pressure hydrocephalus. Br J Radiol. 2025 Jun 1;98(1170):938-946. doi: 10.1093/bjr/tqaf058. PMID: 40088925; PMCID: PMC12089770.
2. Chew EG, Liu Z, Li Z, Chung SJ, Lian MM, Tandiono M, Heng YJ, Ng EY, Tan LC, Chng WL, Tan TJ, Peh EK, Ho YS, Chen XY, Lim EY, Chang CH, Leong JJ, Peh TX, Chan LL, Chao Y, Au WL, Prakash KM, Lim JL, Tay YW, Mok V, Chan AY, Lin JJ, Jeon BS, Song K, Tham CC, Pang CP, Ahn J, Park KH, Wiggs JL, Aung T, Tan AH, Ahmad Annuar A, Makarious MB, Blauwendraat C, Nalls MA, Robak LA, Alcalay RN, Gan-Or Z, Reynolds R, Lim SY, Xia Y, Khor CC, Tan EK, Wang Z, Foo JN. Exome sequencing in Asian populations identifies low-frequency and rare coding variation influencing Parkinson's disease risk. Nat Aging. 2025 Feb;5(2):205-218. doi: 10.1038/s43587-024-00760-7. Epub 2024 Nov 21. PMID: 39572736; PMCID: PMC11839463.
3. Sohn B, Chung SJ, Lee JR, Hwang D, Xie W, Chan LL, Choi YS. 18F-FDG-PET-based deep learning for predicting cognitive decline in non-demented elderly across the Alzheimer's disease clinical spectrum. Radiology Advances. 2024 Sep 14;1(3). doi.org/10.1093/radadv/umae021
4. Welton T, Hartono S, Lee W, Teh PY, Hou W, Chen RC, Chen C, Lim EW, Prakash KM, Tan LCS, Tan EK, Chan LL. Classification of Parkinson's disease by deep learning on midbrain MRI. Front Aging Neurosci. 2024 Aug 20;16:1425095. doi: 10.3389/fnagi.2024.1425095. PMID: 39228827; PMCID: PMC11369979.
5. Hartono S, Chen RC, Welton T, Tan AS, Lee W, Teh PY, Chen C, Hou W, Tham WP, Lim EW, Prakash KM, Shih YC, Lee KJ, Tan LCS, Tan EK, Chan LL. Quantitative iron-neuromelanin MRI associates with motor severity in Parkinson's disease and matches radiological disease classification. Front Aging Neurosci. 2023 Nov 27;15:1287917. doi: 10.3389/fnagi.2023.1287917. PMID: 38090717; PMCID: PMC10711072.
6. Welton T, Hartono S, Shih YC, Schwarz ST, Xing Y, Tan EK, Auer DP, Harel N, Chan LL. Ultra-high-field 7T MRI in Parkinson's disease: ready for clinical use?-a narrative review. Quant Imaging Med Surg. 2023 Nov 1;13(11):7607-7620. doi: 10.21037/qims-23-509. Epub 2023 Oct 17. PMID: 37969629; PMCID: PMC10644128.
7. Ong YL, Deng X, Li HH, Narasimhalu K, Chan LL, Prakash KM, Au WL, Ratnagopal P, Tan LCS, Tan EK. Caffeine intake interacts with Asian gene variants in Parkinson's disease: a study in 4488 subjects. Lancet Reg Health West Pac. 2023 Sep 4;40:100877. doi: 10.1016/j.lanwpc.2023.100877. PMID: 37691886; PMCID: PMC10485627.
8. Shih YC, Ooi LQR, Li HH, Allen JC, Hartono S, Welton T, Tan EK, Chan LL. Serial deep gray nuclear DTI changes in Parkinson's disease over twelve years. Front Aging Neurosci. 2023 Jun 20;15:1169254. doi: 10.3389/fnagi.2023.1169254. PMID: 37409008; PMCID: PMC10318173.
9. Welton T, Hartono S, Shih YC, Lee W, Chai PH, Chong SL, Ng SYE, Chia NSY, Choi X, Heng DL, Tan EK, Tan LCS, Chan LL. Microstructure of Brain Nuclei in Early Parkinson's Disease: Longitudinal Diffusion Kurtosis Imaging. J Parkinsons Dis. 2023 Mar;13(2):233-242. doi: 10.3233/JPD-225095. PMID: 36744346; PMCID: PMC10041414.
10. Welton T, Tan YJ, Saffari SE, Ng SYE, Chia NSY, Yong ACW, Choi X, Heng DL, Shih YC, Hartono S, Lee W, Xu Z, Tay KY, Au WL, Tan EK, Chan LL, Ng ASL, Tan LCS. Plasma Neurofilament Light Concentration Is Associated with Diffusion-Tensor MRI-Based Measures of Neurodegeneration in Early Parkinson's Disease. J Parkinsons Dis. 2022;12(7):2135-2146. doi: 10.3233/JPD-223414. PMID: 36057833.
11. Tan S, Hartono S, Welton T, Ann CN, Lim SL, Koh TS, Li H, Setiawan F, Ng S, Chia N, Liu S, Haacke ME, Tan EK, Tan LCS, Chan LL. Utility of quantitative susceptibility mapping and diffusion kurtosis imaging in the diagnosis of early Parkinson's disease. Neuroimage Clin. 2021;32:102831. doi: 10.1016/j.nicl.2021.102831. Epub 2021 Sep 22. PMID: 34619654; PMCID: PMC8503579.
12. Fang E, Fartaria MJ, Ann CN, Maréchal B, Kober T, Lim JX, Ooi LQR, Chen C, Lim SL, Tan EK, Chan LL. Clinical Correlates of White Matter Lesions in Parkinson’s Disease Using Automated Multi-Modal Segmentation Measures. J Neurol Sci. 2021 May 31. Doi: 10.1016/j.jns.2021.117518
13. Chan LL, Chen R, Li H, Lee AJY, Go WY, Lee W, Lock C, Kumar S, Ng ASL, Kandiah N, Tan LCS, Tan EK, Keong NCH. The splenial angle: a novel radiological index for idiopathic normal pressure hydrocephalus. Eur Radiol. 2021 May 15. Doi: 10.1007/s00330-021-07871-4.
14. Lee WL, Lee A, Li HH, Ong NYX, Keong N, Chen R, Chan LL. Callosal angle in idiopathic normal pressure hydrocephalus: small angular mal-rotations of the coronal plane affect measurement reliability. Neuroradiology 2021 Feb 5:1-9.
15. Fang E, Ann CN, Marechal B, Lim JX, Tan SYZ, Li HH, Gan J, Tan EK, Chan LL. Differentiating Parkinson’s disease motor subtypes using automated volume‐based morphometry incorporating white matter and deep gray nuclear lesion load. J Magn Reson Imaging. 2020 51(3):748-756.
16. Ooi LQR, Wen MC, Ng SYE, Chia NSY, Chew IHM, Lee WL, Xu Z, Hartono S, Tan EK, Chan LL, Tan LCS. Increased activation of default mode network in early Parkinson’s with excessive daytime sleepiness. Increased Activation of Default Mode Network in Early Parkinson's With Excessive Daytime Sleepiness. Front Neurosci. 2019 Dec 12;13:1334.
17. Tan SYZ, Keong NCH, Malathi R, Li HH, Ooi LQR, Tan EK, Chan LL. Periventricular White Matter Abnormalities on Diffusion Tensor Imaging of Postural Instability Gait Disorder Parkinsonism. AJNR Am J Neuroradiol. 2019 Apr;40(4):609-613. doi: 10.3174/ajnr.A5993.
18. Wen MC, Ng SYE, Heng HSE, Chao YX, Chan LL, Tan EK, Tan LCS. Neural substrates of excessive daytime sleepiness in early drug naive Parkinson's disease: A resting state functional MRI study. Parkinsonism Relat Disord. 2016;24:63-8.
19. Tan WQ, Yeoh CS, Rumpel H, Nadkarni N, Lye WK, Tan EK, Chan LL. Deterministic Tractography of the Nigrostriatal-Nigropallidal Pathway in Parkinson's Disease. Sci Rep 2015 Dec 1;5:17283.
20. Chan LL, Ng KM, Rumpel H, Fook-Chong S, Li HH, Tan EK. Transcallosal diffusion tensor abnormalities in predominant gait disorder parkinsonism. Parkinsonism Relat Disord. 2014 Jan;20(1):53-9.