Abstract
There is no well-established in vivo marker of nigral degeneration in Parkinson's disease (PD). An ideal imaging marker would directly mirror the loss of substantia nigra dopaminergic neurones, which is most prominent in sub-regions called nigrosomes. High-resolution, iron-sensitive, magnetic resonance imaging (MRI) at 7T allows direct nigrosome-1 visualisation in healthy people but not in PD. Here, we investigated the feasibility of nigrosome-1 detection using 3T - susceptibility-weighted (SWI) MRI and the diagnostic accuracy that can be achieved for diagnosing PD in a clinical population. 114 high-resolution 3T – SWI-scans were reviewed consisting of a prospective case-control study in 19 subjects (10 PD, 9 controls) and a retrospective cross-sectional study in 95 consecutive patients undergoing routine clinical SWI-scans (>50 years, 9 PD, 81 non-PD, 5 non-diagnostic studies excluded). Two raters independently classified subjects into PD and non-PD according to absence or presence of nigrosome-1, followed by consensus reading. Diagnostic accuracy was assessed against clinical diagnosis as gold standard. Absolute inter- and intra-rater agreement was ≥94% (kappa≥0.82, p<0.001). In the prospective study 8/9 control and 8/10 PD; and in the retrospective study 77/81 non-PD and all 9 PD subjects were correctly classified. Diagnostic accuracy of the retrospective cohort was: sensitivity 100%, specificity 95%, NPV 1, PPV 0.69 and accuracy 96% which dropped to 91% when including non-diagnostic scans (‘intent to diagnose’). The healthy nigrosome-1 can be readily depicted on high-resolution 3T - SWI giving rise to a ‘swallow tail’ appearance of the dorsolateral substantia nigra, and this feature is lost in PD. Visual radiological assessment yielded a high diagnostic accuracy for PD vs. an unselected clinical control population. Assessing the substantia nigra on SWI for the typical ‘swallow tail’ appearance has potential to become a new and easy applicable 3T MRI diagnostic tool for nigral degeneration in PD.
Highlights
Parkinson’s disease (PD) is a progressive neurodegenerative disorder resulting in characteristic motor and non-motor symptoms
DaTscan is not currently licensed for differentiation of some of the parkinsonian conditions that can be mistaken for PD, including progressive supranuclear gaze palsy parkinsonian variant (PSP-P) and multiple system atrophy type P (MSA-P) [6]
Translating this technique to 3T - magnetic resonance imaging (MRI) platforms in order to support the diagnosis of PD would be highly desirable, as MRI at 3T is widely available and much less expensive than licensed nuclear medical techniques. It offers the opportunity for combining diagnostic confirmation of nigral degeneration in PD with promising MRI techniques for differentiating other parkinsonian conditions such as PSP-P, MSA-P and vascular parkinsonism [12,13]. In this combined prospective and retrospective study including 114 SWI scans at 3T, we investigated the feasibility of high resolution T2*/SWI (HR-SWI) MRI at 3T to depict PD related signal loss within nigrosome-1 and the diagnostic accuracy that can be achieved in a clinical population (50+ years of age)
Summary
Parkinson’s disease (PD) is a progressive neurodegenerative disorder resulting in characteristic motor and non-motor symptoms. Ioflupane (123I) single photon emission computer tomography (SPECT) has proved useful in establishing presynaptic dopaminergic loss in difficult diagnostic cases [5] using dopamine transporter imaging of the striatum as a surrogate marker for nigral dopaminergic cell loss. This technique has been recently approved by the American Food and Drug Administration for diagnostic purposes in PD (DaTscan, approved January 2011). These types of scans are expensive, involve low dose radiation and are only available in specialised centres. DaTscan is not currently licensed for differentiation of some of the parkinsonian conditions that can be mistaken for PD, including progressive supranuclear gaze palsy parkinsonian variant (PSP-P) and multiple system atrophy type P (MSA-P) [6]
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