The 'swallow tail' appearance of the healthy nigrosome - a new accurate test of Parkinson's disease: a case-control and retrospective cross-sectional MRI study at 3T

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.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1. Substantia nigra anatomy on 3T - SWI – MRI.

Demonstrated is a 3T - SWI axial slice just at the level of nigrosome-1 with magnification of the midbrain structures and a sketch outlining relevant anatomical structures: 1 red nucleus, 2 midbrain tegmentum, 3 aqueduct, 4 periaqueductal grey, 5 medial leminiscus, 6 nigrosome-1, 7 substantia nigra, 8 cerebral peduncle, 9 mammillary body, 10 inter-peduncular fossa, 11 optic radiation, 12 3rd ventricle, 13 temporal lobe, 14 cerebellum, 15 frontal lobe.

Figure 2. The red rumped swallow (Cecropis daurica).

The tail of the swallow resembles the appearance of the healthy nigrosome-1 on HR-SWI MRI. Picture modified from Wikipedia: http://en.wikipedia.org/wiki/Swallow. Image rights transferred to public domain.

Figure 3. SWI MRI in PD and Non-PD patients.

A. High resolution SWI MRI (3D gradient echo EPI, magnitude image) of a PD patient (left, 60 years, female, UPDRS: 53, HY score 3, nigrosome-1 absent bilaterally) and a control (right, 61 years, female, nigrosome-1 present bilaterally). B. Clinical high resolution 3D-T2*/SWI MRI (Philips ‘PRESTO’ sequence), of a PD patient (left, 58 years old, male, nigrosome-1 absent bilaterally) and a non-PD patient (right, 70 years old, female, diagnosed with an aneurysmal subarachnoid haemorrhage, nigrosome-1 present bilaterally).

Figure 4. Clinical HR-SWI MRI at 3T (‘PRESTO’ sequence) to demonstrate nigrosome-1.

Nigrosome-1 assessment of the SN in 4 different patients (a-d). The first column illustrates the standard axial plane at the level just inferior to red nucleus and the second column the multi-planar reformat along the axis of the low density signal of the SN (oblique axial). Green arrow tip illustrates nigrosome-1 presence; red arrow tip illustrates unclear/possible presence of nigrosome-1. a) Non-PD patient (60 years old, female, diagnosed with cognitive impairment and a small cerebral cavernoma) – nigrosome-1 is present bilaterally. b) Non-PD patient (54 year old, female, MRI scan for recurrent loss of consciousness of unknown cause) – nigrosome-1 is present bilaterally but smaller than in (a). c) PD patient (68 years old, male) - Right nigrosome-1 absent, left nigrosome-1 unclear. d) PD patient (65 years old, female) – nigrosome-1 absent bilaterally. An example of Group II (bilateral unclear/possible nigrosome-1 presence, n = 2 of 81 non-PD patients) is not demonstrated.