Virtual definition of neuronal tissue by cluster analysis of multi-parametric imaging (virtual-dot-com imaging)

Individual mapping of cerebral, morphological, functionally related structures using MRI was carried out using a new multi-contrast acquisition and analysis framework, called virtual-dot-com imaging. So far, conventional anatomical MRI has been able to provide gross segmentation of gray/white matter boundaries and a few sub-cortical structures. By combining a handful of imaging contrasts mechanisms (T1, T2, magnetization transfer, T2* and proton density), we were able to further segment sub-cortical tissue to its sub-nuclei arrangement, a segmentation that is difficult based on conventional, single-contrast MRI. Using an automatic four-step image and signal processing algorithm, we segmented the thalamus to at least 7 sub-nuclei with high similarity across subjects and high statistical significance within subjects (p < 0.0001). The identified sub-nuclei resembled the known anatomical arrangement of the thalamus given in various atlases. Each cluster was characterized by a unique MRI contrast fingerprint. With this procedure, the weighted proportions of the different cellular compartments could be estimated, a property available to date only by histological analysis. Each sub-nucleus could be characterized in terms of normalized MRI contrast and compared to other sub-nuclei. The different weights of the contrasts (T1/T2/T2*/PD/MT, etc.) for each sub-nuclei cluster might indicate the intra-cluster morphological arrangement of the tissue that it represents. The implications of this methodology are far-ranging, from non-invasive, in vivo, individual mapping of histologically distinct brain areas to automatic identification of pathological processes.