Neuromelanin-sensitive magnetic resonance imaging (NM-MRI) has emerged as a promising biomarker for Parkinson’s disease (PD) research. Historically, imaging in PD has relied primarily on nuclear medicine techniques such as dopamine transporter (DAT) scans, as patients with PD do not exhibit robust, disease-specific patterns of brain atrophy detectable with conventional structural MRI.

Neuromelanin-sensitive MRI is challenging this paradigm. Neuromelanin (NM) is a dark pigment, believed to be a byproduct of dopamine and norepinephrine metabolism. It is particularly found in the dopaminergic neurons of the substantia nigra (SN) and the norepinephrine (noradrenergic) neurons of the locus coeruleus. By providing a surrogate measure of neural integrity in these regions, NM-MRI offers a non-invasive window into neuronal health during disease progression. Increasing research suggests that measuring changes in NM-MRI signal in these regions can improve sensitivity for early diagnosis, disease staging, and monitoring therapeutic efficacy.

Why Neuromelanin is Relevant in PD Clinical Research

NM-MRI correlates with motor symptom severity and may detect subtle neuronal changes before overt clinical manifestations. This has led to growing interest in NM-MRI as a biomarker for early PD, disease progression, and treatment response.

Preliminary results from the Prasinezumab program (sponsored by Roche) reported modest trend-level reductions in SN NM signal in treatment cohorts compared with placebo, supporting its feasibility as a longitudinal efficacy biomarker. Other early clinical trials have reported modest but consistent declines in NM signal associated with motor deterioration and response to dopaminergic therapies. While sample sizes remain limited, these findings highlight NM-MRI’s potential to inform trial design, track disease-modifying interventions, and identify preclinical PD.

Beyond PD, NM-MRI is gaining traction in therapeutic areas such as schizophrenia, where studies have found that the NM signal in the SN correlates with the severity of psychosis. As disrupted catecholaminergic (dopaminergic and noradrenergic) function contributes to many psychiatric disorders, NM-MRI is being explored as a potential biomarker in many conditions, including depression, bipolar disorder, and post-traumatic stress disorder.

This, however, is still an emerging area of research, and questions remain regarding the MRI sequence and the method of analysis applied. The majority of NM imaging pipelines focus on two sequences: magnetisation transfer–prepared gradient-echo (MT-GRE) and T1-weighted turbo spin-echo (TSE).

MT-GRE sequences are highly sensitive to NM due to their ability to exploit magnetisation transfer effects, producing strong contrast between NM-rich regions and surrounding tissue. TSE acquisitions, while slightly less sensitive, offer robust signal-to-noise ratios and reduced susceptibility to artefacts, and with fewer parameter adjustments, are easier to standardise across multi-site trials.

Additional imaging factors such as scan time, specific absorption rate (SAR), spatial coverage, and susceptibility to artefacts also require consideration when optimising NM-sensitive protocols.

In practical terms, MT-GRE sequences are generally faster, impose lower SAR and may offer greater sensitivity for detecting subtle NM loss in comparison to TSE, but require careful calibration and higher operator expertise. TSE sequences, on the other hand, are easier to implement across clinical sites with varied scanner hardware due to their robustness and standardised acquisition settings and are less sensitive to susceptibility artefacts owing to the use of refocusing pulses.

This balance of harmonisation and image sensitivity is a critical issue in multi-site neuromelanin imaging trials, and the capabilities of sites enrolled must be carefully assessed in the context of the sample size and ability to detect subtle signal change to ensure the data acquired is fit for purpose, whether using one or both of these sequences.

Conclusion

Neuromelanin imaging represents a powerful tool for PD research, enabling non-invasive and highly repeatable assessment of dopaminergic neuron integrity, which is not possible with DAT scans or conventional MRI. While MT-GRE offers high sensitivity, TSE sequences provide practicality for multi-site deployment. Substantia nigra measures, such as volume, contrast, and regional gradients, may allow nuanced tracking of disease progression. Early studies, including Roche’s PADOVA (part of the same Prasinezumap program), demonstrate trend-level changes supporting further exploration in clinical trials.

For researchers and clinicians interested in integrating NM-MRI into PD studies, continued pipeline refinement and cross-site harmonisation are essential next steps.

At IXICO we are actively researching the use of neuromelanin imaging and the utility of NM endpoints for clinical trials in PD and other therapeutic areas. To explore how we can support your program, please get in touch at www.ixico.com/contact-us.

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