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

The protocol presents the first standardized and highly-detailed step-by-step procedure for acquiring neuromelanin-sensitive MRI. This will allow the field to directly compare data across sites and combine samples to validate generalized biomarkers. The technique uses a detailed placement procedure and quality control checks to minimize data loss.

The technique will facilitate large-scale studies necessary to develop and validate biomarkers in neuropsychiatric disorders, particularly for the diagnosis of Parkinson's disease. It is useful to review the basic concepts in neuroanatomy, such as terms for different planes and locations of the brain that allow one to get oriented, while examining brain images on the scanner console. Start by acquiring a high resolution T1-weighted or T1W image of a maximum one millimeter isotropic voxel size that is aligned along the anterior commissure, posterior commissure or AC-PC line and the midline.

Immediately after the acquisition, perform the alignment of the high resolution T1W image through online reformatting with the compatible software. Load the sagittal, coronal, and axial views of the AC-PC-aligned T1W image and ensure that the reference lines depicting the location of each displayed slice are present. Next, visually inspect the sagittal slices of the reformatted image to identify the sagittal image showing the largest separation between the mid-brain and thalamus.

Use the sagittal image to visually identify the coronal plane, delineating the most anterior aspect of the mid-brain. In the coronal image, visually identify the axial plane that outlines the inferior aspect of the third ventricle. On the sagittal image, align the superior boundary of the NM-MRI volume to the axial plane identified earlier.

Then, move the superior boundary of the NM-MRI volume three millimeters in the superior direction. Similarly, align the NM-MRI volume to the midline in the axial and coronal images and acquire the NM-MRI images. Perform quality control checks on the acquired NM-MRI images by ensuring that the images cover the entire substantia nigra or SN.Confirm that the SN is visible in the central images, but not in the most superior or most inferior images of the NM-MRI volume.

If the NM-MRI images fail the preliminary quality control check, repeat the T1-weighted acquisition, NM-MRI placement procedure, and acquisition. Next, visually inspect each slice of the acquired NM-MRI scan to check for artifacts. Check for artifacts that go through the SN and the surrounding white matter.

Look for abrupt changes in signal intensity with a linear pattern that does not respect normal anatomical boundaries. NM-MRI images with artifacts resulting from blood vessels should be retained, as these artifacts will most likely always be present. If the artifacts are due to the participants'head motion or are ambiguous, copy the NM-MRI volume placement and reacquire the NM-MRI images.

Upon reacquisition, if the artifacts remain present, proceed with these images, as they could be biological rather than a result of motion. The protocol ensures the acquisition of satisfactory NM-MRI images with complete coverage of the SN in a stepwise manner. In the initial quality check of acquired images, the SN was visible in the most superior slice, indicating that full coverage of the SN was not achieved.

The images failed the second quality check due to the presence of artifacts resulting from blood vessels, artifacts resulting from motion, or ambiguous artifacts. In the representative analysis, the satisfactory NM-MRI images from most inferior to most superior are displayed. On the images, excellent contrast between the SN and neighboring white matter regions with no neuromelanin concentration could be seen.

The procedure ensures that good quality neuromelanin-sensitive MRI data is acquired in a reliable and repeatable fashion. The data can be used to non-invasively investigate dopamine cell loss in neurodegenerative diseases.