Optimizing neuromelanin contrast in the substantia nigra and locus coeruleus using a magnetization transfer contrast prepared 3D gradient recalled echo sequence

Neuromelanin (NM) loss in the substantia nigra (SN) and locus coeruleus (LC) is being investigated as an imaging biomarker for Parkinson's disease (PD) using magnetization transfer contrast (MTC) magnetic resonance imaging. The MTC pulse operates in a way to suppress tissue with high macromolecular content thereby highlighting the presence of NM in the LC and the SN. The MTC pulse also leads to a reduction in the effective T1 of the tissue. In the past, a 3D gradient echo (GRE) sequence has usually been run with a single flip angle (FA) generally to highlight the T1 shortening effect when trying to visualize NM. We contend that the NM will be best seen with a low FA (relative to the Ernst angle) because the NM has high water content relative to the surrounding tissues. Therefore, the goal of this paper was to optimize the NM contrast in the SN and LC as a function of flip angle using a 3D GRE MTC strategically acquired gradient echo (STAGE) imaging approach. In order to accomplish this, short repeat time (62 ​ms), 3D GRE imaging data were collected for 7 different flip angles ranging from 5° to 40° for 14 healthy volunteers (age range 24-43 years, mean ​± ​SD ​= ​34.8 ​± ​6.0 years, 6 males). By measuring the contrast-to-noise ratio between these structures and the surrounding tissues, we found that the FA showing the best NM contrast was 15° - 20° for the SN and 20° - 25° for the LC. Using STAGE imaging with just two flip angles (15° and 30°) made it possible to quantify not only tissue properties such as T1 and proton density but also to generate synthetic MTC images at an arbitrary FA. These synthetic images make it possible to optimize the contrast for any changes in tissue property that might occur in the LC or SN as a function of age or disease. In conclusion, practically, two scans could be collected in roughly 7 ​min each for both FAs in a standard clinical imaging setting to evaluate the signal intensity and volume of the NM in the LC and SN.