A major impediment to research on the neural basis of functional heterogeneity in PD is a paucity of safe, fast, and effective brain imaging methods for visualizing the affected structures. This ineffectiveness is due predominantly to the limited contrast of most current MRI methods [3
], which are unable to detect PD abnormalities. Because conventional structural MRI techniques cannot visualize the brain changes that are at the core of this disease, progress in developing MRI-based biomarkers for diagnosing and tracking disease progression has been slow.
A few methods for imaging the SNpc have met with some success, such as evaluation of T2 relaxation times [5
], T2*- and diffusion-weighted imaging [6
], inversion-recovery sequences [7
], and proton density-weighted imaging [8
]. Other studies have resolved the basal forebrain on T2-weighted images, demonstrating reduced thickness of this structure in mildly demented PD patients, compared to controls [9
]. A limitation of these previous structural neuroimaging studies, however, is that the MRI sequences were typically optimized to resolve one particular structure, and, therefore, were not well suited for visualizing other brain areas. We recently reported new multispectral MRI methods that begin to reverse this serious shortcoming [10
], paving the way to the development of new MRI-based biomarkers that are capable of detecting subcortical brain abnormalities in early stages of the disease.
Traditionally, the MPRAGE scan has been the gold standard for performing morphometric analyses, such as volumetrics [11
] and surface-based analyses [12
], because the resulting T1-weighting provides relatively good contrast between gray matter, white matter, and cerebrospinal fluid. The MPRAGE scan is less useful, however, for distinguishing subcortical structures, because T1-weighting doesn’t provide sufficient contrast between small, neighboring gray matter nuclei. Additional morphometric information can be obtained through different sequences, such as T2-SPACE [13
] and multiecho FLASH (ME-FLASH) [14
]. Combining these different scans is complicated by variability in their relative distortions resulting from different bandwidths among these sequences. The T2-SPACE and ME-FLASH employ a high bandwidth, while maintaining good signal-to-noise; however, the conventional MPRAGE requires a lower bandwidth in order to achieve comparable signal-to-noise. Differing bandwidths lead to massive variations in the B0 distortions, resulting in images that are not able to be coregistered.