Neuromelanin MRI and nigrosome sign

The research record

This is the project's file for this landmark, as written and checked. Sources are listed at the end; anything not yet confirmed is marked "Not yet verified".

Who

Makoto Sasaki and colleagues (Iwate Medical University, Japan), Neuroreport 2006. Stephan Schwarz, Dorothee Auer and colleagues (University of Nottingham), PLoS One 2014. Funders were not stated in the abstracts and were not checked.

What happened

• Neuromelanin MRI (2006): neuromelanin is the dark pigment in dopamine and noradrenaline neurons (landmark 128). A new 3T technique showed it as bright areas in the locus ceruleus and substantia nigra pars compacta. In Parkinson's patients the signal was greatly reduced, suggesting loss of pigmented neurons.
• Nigrosome-1 sign (2014): nigrosome-1 is the sub-region of the nigra with the heaviest cell loss, the kind of focal, early nigral loss mapped in landmark 267. On high-resolution 3T susceptibility-weighted MRI it looks like a "swallow tail". Schwarz reviewed 114 scans: a prospective case-control group of 19 (10 PD, 9 controls), where 8 of 9 controls and 8 of 10 PD were classified correctly, and a retrospective group of 95 routine clinical scans (9 PD, 81 non-PD, 5 non-diagnostic excluded). In the retrospective group sensitivity was 100%, specificity 95% and accuracy 96%, falling to 91% when non-diagnostic scans were counted. Positive predictive value was only 0.69, because there were so few PD cases. A later 7T study of 26 patients and 15 controls scored nigrosome-1 and the smaller nigrosomes 2 to 5 (the 7T scanner is a research-grade, stronger magnet), and tied signal change to disease severity (Schwarz 2018).
• Later confirmation. A 2020 meta-analysis of 19 studies (903 PD patients, 605 healthy controls) pooled sensitivity 0.94 and specificity 0.90 for visual reading of nigrosome-1 at 3T or 7T (Chau 2020). A 2021 French study of 140 PD patients and 64 controls rescanned some after about 2 years and found the neuromelanin MRI nigral signal and volume fell more in PD than in controls (Gaurav 2021, Mov Disord).

Why it moved us toward a cure

Both read out the very cells a therapy must save or replace, with no radiation or tracer. If they track change over time they could serve as trial endpoints alongside DAT scans (landmark 79) and free-water MRI (landmark 224). Neuromelanin loss is also what a restored-neuron graft should reverse.

Outcome

Open. Both began as diagnostic findings. The nigrosome sign has since been replicated across many centres (the 2020 meta-analysis), and neuromelanin MRI has a longitudinal progression study (Gaurav 2021). Neither is yet an accepted trial endpoint; landmark 224 notes the 2006 paper itself was cross-sectional. No correction or retraction was found for the 2006 or 2014 papers (Crossref and Europe PMC, 19 Oct 2026).

Sources

• Sasaki et al., Neuroreport 2006;17:1215–1218, DOI 10.1097/01.wnr.0000227984.84927.a7
• Schwarz et al., PLoS One 2014;9:e93814, DOI 10.1371/journal.pone.0093814
• Schwarz et al., Neuroimage Clin 2018;19:683–689, DOI 10.1016/j.nicl.2018.05.027
• Chau et al., Parkinsonism Relat Disord 2020;78:12–20, DOI 10.1016/j.parkreldis.2020.07.002 (PubMed 32668370)
• Gaurav et al., Mov Disord 2021;36:1592–1602, DOI 10.1002/mds.28531 (PubMed 33751655)
• Not yet verified: Sasaki's patient numbers (abstract gives none); whether either MRI sign has been used as a trial endpoint.