Optimizing the visualization of the locus coeruleus using magnetization transfer contrast 3D imaging

BACKGROUND: The locus coeruleus (LC) is a key noradrenergic nucleus of the brain. Its dysfunction is implicated in neurodegenerative diseases like Alzheimer's disease and Parkinson's disease, as well as in psychiatric disorders. However, imaging the LC with sufficient contrast-to-noise ratio (CNR) is challenging due to its small size and deep location in the brainstem. This study optimizes a 3D gradient echo (GRE) sequence with magnetization transfer contrast (MTC) to enable rapid, high-resolution LC imaging in under five minutes. METHODS: A high-resolution 3D-GRE-MTC sequence was optimized on a 3T scanner in 11 healthy volunteers (6 young and 5 older adults). Tissue properties were measured using in vivo MRI data, and simulations were performed to identify the optimal flip angle. LC visualization was evaluated by two independent raters using relative contrast ratio (rCR) and CNR. The diameter and the length of the LC were also evaluated. Each volunteer underwent MRI sessions over three days to assess test-retest reliability. The intra-class correlation coefficient (ICC) for inter-rater reliability and the mean ± standard deviation of LC rCR across sessions for test-retest reproducibility were calculated. RESULTS: A total of 98 scans were collected. The optimized protocol achieved 0.67 × 0.73 × 2 mm³ resolution with an 18° flip angle, 6.18 ms first echo, 52 ms repetition time, flow compensation, arterial suppression, and strict head immobilization. The LC exhibited a CNR of 8.27 ± 1.03, and rCR of 16.70% ± 1.77% (left) and 13.97% ± 2.19% (right), with good inter-rater reliability (ICC = 88.51%). Contrast stability between scans had a variability of 4%-11%. The bilateral LC was visible across 3-6 slices (6-12 mm). Using the full width at quarter maximum measure, the LC diameter was 1.94 ± 0.40 mm for the left side and 1.67 ± 0.34 mm for the right side. CONCLUSION: The optimized protocol enabled reliable, high-resolution LC imaging in under five minutes, providing a valuable tool for clinical and research applications.