Standardized Data Acquisition for Neuromelanin-Sensitive Magnetic Resonance Imaging of the Substantia Nigra

Summary

This protocol shows how to acquire neuromelanin-sensitive magnetic resonance imaging data of the substantia nigra.

Abstract

The dopaminergic system plays a crucial role in healthy cognition (e.g., reward learning and uncertainty) and neuropsychiatric disorders (e.g., Parkinson's disease and schizophrenia). Neuromelanin is a byproduct of dopamine synthesis that accumulates in dopaminergic neurons of the substantia nigra. Neuromelanin-sensitive magnetic resonance imaging (NM-MRI) is a noninvasive method for measuring neuromelanin in those dopaminergic neurons, providing a direct measure of dopaminergic cell loss in the substantia nigra and a proxy measure of dopamine function. Although NM-MRI has been shown to be useful for studying various neuropsychiatric disorders, it is challenged by a limited field-of-view in the inferior-superior direction resulting in the potential loss of data from the accidental exclusion of part of the substantia nigra. In addition, the field is lacking a standardized protocol for the acquisition of NM-MRI data, a critical step in facilitating large-scale multisite studies and translation into the clinic. This protocol describes a step-by-step NM-MRI volume placement procedure and online quality control checks to ensure the acquisition of good-quality data covering the entire substantia nigra.

Introduction

Neuromelanin (NM) is a dark pigment found in dopaminergic neurons of the substantia nigra (SN) and noradrenergic neurons of the locus coeruleus (LC)^1,2. NM is synthesized by the iron-dependent oxidation of cytosolic dopamine and norepinephrine and is stored in autophagic vacuoles in the soma³. It first appears in humans around 2-3 years of age and accumulates with age^1,4,5.

Within the NM-containing vacuoles of SN and LC neurons, NM forms complexes with iron. These NM....

Protocol

NOTE: The research conducted to develop this protocol was performed in compliance with New York State Psychiatric Institute Institutional Review Board guidelines (IRB #7655). One subject was scanned for recording the protocol video, and written informed consent was obtained. Refer to the Table of Materials for details about the MRI scanner used in this protocol.

1. MRI acquisition parameters

1. Prepare to acquire high-resolution T1w images using a 3D magnetization prepared rapid acquisition gradient echo (MPRAGE) sequence with the following parameters: spatial resolution = 0.8 x 0.8 x 0.8 mm³; field-of-v....

Results

Figure 4 shows the representative results from a 28-year-old female participant with no psychiatric or neurological disorders. The NM-MRI protocol ensures complete coverage of the SN, achieved by following step 2 of the protocol outlined in Figure 1, and satisfactory NM-MRI images by following step 3 of the protocol. Excellent contrast between the SN and neighboring white matter regions with negligible NM concentration (i.e., crus cerebri) can be seen. Thes.......

Discussion

The dopaminergic system plays a crucial role in healthy cognition and neuropsychiatric disorders. The development of noninvasive methods that can be used to repeatedly investigate the dopaminergic system in vivo is critical for the development of clinically meaningful biomarkers. The protocol described here supplies step-by-step instructions for acquiring good-quality NM-MRI images of the SN, including placement of the NM-MRI volume and quality control checks to ensure usable data.

Ev.......

Materials

Name	Company	Catalog Number	Comments
3T Magnetic Resonance Imaging	General Electric		GE SIGNA Premier with 48-channel head coil