Nigrosome neuromelanin loss at 3T MRI has diagnostic value in clinical uncertain parkinsonism
Poster No:
305
Submission Type:
Abstract Submission
Authors:
Yue Xing1,2,3, Stefan Pszczolkowski1,2,3, Saadnah Naidu1,2, Marta Gennaro4,5, Andreas-Antonios Roussakis6, Tayyib Hayat1,2,7, Jonathan Evans7, Antonio Martin-Bastida4,8, Christopher Tench1,3, Paola Piccini4,6,9, Stefan Schwarz1,2,10, Dorothee Auer1,2,3
Institutions:
1Mental Health and Clinical Neurosciences Unit, University of Nottingham, Nottingham, United Kingdom, 2Sir Peter Mansfield Imaging Centre, School of Medicine, University of Nottingham, Nottingham, United Kingdom, 3NIHR Nottingham Biomedical Research Centre, Queen’s Medical Centre, University of Nottingham, Nottingham, United Kingdom, 4Division of Neurology, Imperial College London, London, United Kingdom, 5Nuclear Medicine Department, Royal Brompton & Harefield Hospitals, Guy’s and St Thomas’ NHS Foundation Trust, London, United Kingdom, 6NHLI Department, Imperial College London, Hammersmith Campus, London, United Kingdom, 7Department of Neurology, Nottingham University Hospitals, Nottingham, United Kingdom, 8Department of Neurology and Neurosciences, Clínica Universidad de Navarra, Pamplona-Madrid, Spain, 9Department of Brain Science, Imperial College London, London, United Kingdom, 10Department of Radiology, Cardiff and Vale University Health Board, Cardiff, United Kingdom
First Author:
Yue Xing
Mental Health and Clinical Neurosciences Unit, University of Nottingham|Sir Peter Mansfield Imaging Centre, School of Medicine, University of Nottingham|NIHR Nottingham Biomedical Research Centre, Queen’s Medical Centre, University of Nottingham
Nottingham, United Kingdom|Nottingham, United Kingdom|Nottingham, United Kingdom
Mental Health and Clinical Neurosciences Unit, University of Nottingham|Sir Peter Mansfield Imaging Centre, School of Medicine, University of Nottingham|NIHR Nottingham Biomedical Research Centre, Queen’s Medical Centre, University of Nottingham
Nottingham, United Kingdom|Nottingham, United Kingdom|Nottingham, United Kingdom
Co-Author(s):
Stefan Pszczolkowski
Mental Health and Clinical Neurosciences Unit, University of Nottingham|Sir Peter Mansfield Imaging Centre, School of Medicine, University of Nottingham|NIHR Nottingham Biomedical Research Centre, Queen’s Medical Centre, University of Nottingham
Nottingham, United Kingdom|Nottingham, United Kingdom|Nottingham, United Kingdom
Mental Health and Clinical Neurosciences Unit, University of Nottingham|Sir Peter Mansfield Imaging Centre, School of Medicine, University of Nottingham|NIHR Nottingham Biomedical Research Centre, Queen’s Medical Centre, University of Nottingham
Nottingham, United Kingdom|Nottingham, United Kingdom|Nottingham, United Kingdom
Saadnah Naidu
Mental Health and Clinical Neurosciences Unit, University of Nottingham|Sir Peter Mansfield Imaging Centre, School of Medicine, University of Nottingham
Nottingham, United Kingdom|Nottingham, United Kingdom
Mental Health and Clinical Neurosciences Unit, University of Nottingham|Sir Peter Mansfield Imaging Centre, School of Medicine, University of Nottingham
Nottingham, United Kingdom|Nottingham, United Kingdom
Marta Gennaro
Division of Neurology, Imperial College London|Nuclear Medicine Department, Royal Brompton & Harefield Hospitals, Guy’s and St Thomas’ NHS Foundation Trust
London, United Kingdom|London, United Kingdom
Division of Neurology, Imperial College London|Nuclear Medicine Department, Royal Brompton & Harefield Hospitals, Guy’s and St Thomas’ NHS Foundation Trust
London, United Kingdom|London, United Kingdom
Andreas-Antonios Roussakis
NHLI Department, Imperial College London, Hammersmith Campus
London, United Kingdom
NHLI Department, Imperial College London, Hammersmith Campus
London, United Kingdom
Tayyib Hayat
Mental Health and Clinical Neurosciences Unit, University of Nottingham|Sir Peter Mansfield Imaging Centre, School of Medicine, University of Nottingham|Department of Neurology, Nottingham University Hospitals
Nottingham, United Kingdom|Nottingham, United Kingdom|Nottingham, United Kingdom
Mental Health and Clinical Neurosciences Unit, University of Nottingham|Sir Peter Mansfield Imaging Centre, School of Medicine, University of Nottingham|Department of Neurology, Nottingham University Hospitals
Nottingham, United Kingdom|Nottingham, United Kingdom|Nottingham, United Kingdom
Antonio Martin-Bastida
Division of Neurology, Imperial College London|Department of Neurology and Neurosciences, Clínica Universidad de Navarra
London, United Kingdom|Pamplona-Madrid, Spain
Division of Neurology, Imperial College London|Department of Neurology and Neurosciences, Clínica Universidad de Navarra
London, United Kingdom|Pamplona-Madrid, Spain
Christopher Tench
Mental Health and Clinical Neurosciences Unit, University of Nottingham|NIHR Nottingham Biomedical Research Centre, Queen’s Medical Centre, University of Nottingham
Nottingham, United Kingdom|Nottingham, United Kingdom
Mental Health and Clinical Neurosciences Unit, University of Nottingham|NIHR Nottingham Biomedical Research Centre, Queen’s Medical Centre, University of Nottingham
Nottingham, United Kingdom|Nottingham, United Kingdom
Paola Piccini
Division of Neurology, Imperial College London|NHLI Department, Imperial College London, Hammersmith Campus|Department of Brain Science, Imperial College London
London, United Kingdom|London, United Kingdom|London, United Kingdom
Division of Neurology, Imperial College London|NHLI Department, Imperial College London, Hammersmith Campus|Department of Brain Science, Imperial College London
London, United Kingdom|London, United Kingdom|London, United Kingdom
Stefan Schwarz
Mental Health and Clinical Neurosciences Unit, University of Nottingham|Sir Peter Mansfield Imaging Centre, School of Medicine, University of Nottingham|Department of Radiology, Cardiff and Vale University Health Board
Nottingham, United Kingdom|Nottingham, United Kingdom|Cardiff, United Kingdom
Mental Health and Clinical Neurosciences Unit, University of Nottingham|Sir Peter Mansfield Imaging Centre, School of Medicine, University of Nottingham|Department of Radiology, Cardiff and Vale University Health Board
Nottingham, United Kingdom|Nottingham, United Kingdom|Cardiff, United Kingdom
Dorothee Auer
Mental Health and Clinical Neurosciences Unit, University of Nottingham|Sir Peter Mansfield Imaging Centre, School of Medicine, University of Nottingham|NIHR Nottingham Biomedical Research Centre, Queen’s Medical Centre, University of Nottingham
Nottingham, United Kingdom|Nottingham, United Kingdom|Nottingham, United Kingdom
Mental Health and Clinical Neurosciences Unit, University of Nottingham|Sir Peter Mansfield Imaging Centre, School of Medicine, University of Nottingham|NIHR Nottingham Biomedical Research Centre, Queen’s Medical Centre, University of Nottingham
Nottingham, United Kingdom|Nottingham, United Kingdom|Nottingham, United Kingdom
Introduction:
Pigmentation loss of nigrosome 1 (NS1) in the substantia nigra on neuromelanin-sensitive MRI (NM-MRI) is now well established as early sign of clinical Parkinson's (Sung, 2021). It remains unclear whether NS1 depigmentation can predict Parkinson disease (PD) even earlier when presenting with clinical uncertan parkinsonism (CUP). We aimed to address this as secondary aim of our prospective multi-centre multi-modal imaging study in CUP (Schwarz, 2017). Here we report the diagnostic value of NS1 pigmentation contrast in CUP against the diagnosis of Parkinson's or non-neurodegenerative parkinsonism at clinical follow-up. We also explored the effect of laterality and scanning site on prediction.
Methods:
110 participants (61 [34 males, 31 PD, Site1], 49 [27 males, 37 PD, Site2]) with quality-controlled NM-MRI at 3T (details in (Xing, 2023)) and clinical follow-up (FU) >1 year were included under local ethics approval (Health Research Authority East Midlands – Derby Research Ethics Committee. REC ref.: 16/EM/0229). NM-MRI was analysed using an optimised in-house pipeline (Pszczolkowski, 2023). NS1 ROIs were manually defined on normative susceptibility weighted MRI to derive averaged unilateral and bilateral NS1 pigmentation to background contrasts.
Binary logistic regression was used in cohort1 [Site1] to test the effect of diagnostic status as dependent on the NS1 contrast as independent outcome variable with age and sex as covariates (first bilaterally and then unilateral-contralateral to most affected side in the subgroup with asymmetric presentation, N=60). The effect-size was calculated as adjusted t-values. The test was also repeated in the independent cohort2 [Site2] as cross-site validation.
Binary logistic regression was used in cohort1 [Site1] to test the effect of diagnostic status as dependent on the NS1 contrast as independent outcome variable with age and sex as covariates (first bilaterally and then unilateral-contralateral to most affected side in the subgroup with asymmetric presentation, N=60). The effect-size was calculated as adjusted t-values. The test was also repeated in the independent cohort2 [Site2] as cross-site validation.
Results:
NS1 pigmentation was significantly lower in CUP with FU diagnosis of PD (0.15±0.02) compared to those with other, non-degenerative diagnoses (0.17±0.02, p=0.0005, t=-3.49, Figure1-A) in cohort1 [Site1]. The effect of future diagnosis was confirmed in cohort2 [Site2] (PD-CUP: 0.13±0.02; non-PD: 0.09±0.03, p=0.002, t=-3.1, Figure1-B), despite protocol-dependent differences in NS1 neuromelanin (NM) ratios (nonPD: 0.13±0.02; PD-CUP: 0.09±0.03, p=0.002, t=-3.1). Similar pattern of group difference is shown for unilateral NS1 in Figure2-A and Figure 2-B. Discriminative powers of bilateral and unilateral NS1 are demonstrated for both sites (Figure2-C), with highest AUC values in Site2 that exceeded the diagnostic performance considered to be clinically useful (80% sensitivity and 80% specificity-the estimated point is also shown for visual comparison). This is followed by the unilateral NS1 NM contrasts for cohort2 [Site2] and then bilateral NS1 for cohort1 [Site1], both nearly achieving the clinically useful level. The unilateral NS1 NM contrast for cohort1 [Site1] met the sensitivity but narrowly missed the specificity threshold.
·Group difference of contrast to background values of bilateral SN illustrated with both site 1 (A) and site 2 validation (B) cohorts.
·Site1 (A) and Site2 (B) unilateral group difference of contrast in CUP with asymmetric signs. (C) ROC curves vs. clinically useful sensitivity (80%) and specificity (80%).
Conclusions:
Our results show that MR detectable pigmentation loss of NS1 can be seen in CUP who will later be diagnosed as Parkinson's compared to other non-degenerative causes of Parkinson's. The diagnostic performance of this simple MRI test may be clinically useful with one site achieving predefined sensitivity and specificity with bilateral NS1. Further investigation is on-going to explore improved prediction models by inclusion of available baseline clinical findings including laterality and other MR modalities.
Disorders of the Nervous System:
Neurodegenerative/ Late Life (eg. Parkinson’s, Alzheimer’s) 1
Modeling and Analysis Methods:
Classification and Predictive Modeling 2
Multivariate Approaches
Keywords:
Other - Clinical Uncertain Parkinsonism; Neuromelanin-sensitive MRI
1|2Indicates the priority used for review
Provide references using author date format
Sung, Y. H. (2021). Early‐stage Parkinson's disease: Abnormal nigrosome 1 and 2 revealed by a voxelwise analysis of neuromelanin‐sensitive MRI. Human Brain Mapping, 42(9), 2823-2832.
Schwarz, S. T. (2017). Protocol of a single group prospective observational study on the diagnostic value of 3T susceptibility weighted MRI of nigrosome-1 in patients with parkinsonian symptoms: the N3iPD study (nigrosomal iron imaging in Parkinson’s disease). BMJ open, 7(12), e016904.
Xing, Y. (2023). Nigrosome depigmentation as seen on neuromelanin-sensitive MRI at 3T as diagnostic marker in clinical uncertain parkinsonism: analysis plan for the secondary aims of N3iPD study. Nottingham Research Data Management Repository. https://rdmc.nottingham.ac.uk/handle/internal/10932