Purpose To propose and evaluate a novel multidimensional approach for imaging sub-voxel tissue compartments called Diffusion-Relaxation Correlation Spectroscopic Imaging (DR-CSI). Theory and Methods Multi-exponential modeling of MR diffusion or relaxation data is commonly used to infer the many different microscopic tissue compartments that contribute signal to macroscopic MR imaging voxels. However, multi-exponential estimation is known to be difficult and ill-posed. Observing that this ill-posedness is theoretically reduced in higher dimensions, DR-CSI uses a novel multidimensional imaging experiment that jointly encodes diffusion and relaxation information, and then uses a novel constrained reconstruction technique to generate a multidimensional diffusion-relaxation correlation spectrum for every voxel. The peaks of the multidimensional spectrum are expected to correspond to the distinct tissue microenvironments that are present within each macroscopic imaging voxel. Results Using numerical simulations, experiment data from a custom-built phantom, and experiment data from a mouse model of traumatic spinal cord injury, DR-CSI is demonstrated to provide substantially better multi-compartment resolving power compared to conventional diffusion- and relaxation-based methods. Conclusion The DR-CSI approach provides powerful new capabilities for resolving the different components of multi-compartment tissue models, and can be leveraged to significantly expand the insights provided by MRI in studies of tissue microstructure.

Between birth and late adolescence, the human brain undergoes exponential maturational changes. Using in vivo magnetic resonance spectroscopy, we determined the developmental profile for 6 metabolites in 5 distinct brain regions based on spectra from 309 children from 0 to 18 years of age. The concentrations of N-acetyl-aspartate (an indicator for adult-type neurons and axons), creatine (energy metabolite), and glutamate (excitatory neurotransmitter) increased rapidly between birth and 3 months, a period of rapid axonal growth and synapse formation. Myo-inositol, implicated in cell signaling and a precursor of membrane phospholipid, as well as an osmolyte and astrocyte marker, declined rapidly during this period. Choline, a membrane metabolite and indicator for de novo myelin and cell membrane synthesis, peaked from birth until approximately 3 months, and then declined gradually, reaching a plateau at early childhood. Similarly, taurine, involved in neuronal excitability, synaptic potentiation, and osmoregulation, was high until approximately 3 months and thereafter declined. These data indicate that the first 3 months of postnatal life are a critical period of rapid metabolic changes in the development of the human brain. This study of the developmental profiles of the major brain metabolites provides essential baseline information for future analyses of the pediatric health and disease.

Patients with congenital heart disease (CHD) are at risk for neurocognitive impairments. Little is known about the impact of CHD on the organization of large-scale brain networks. We applied graph analysis techniques to diffusion tensor imaging (DTI) data obtained from 49 adolescents with dextro-transposition of the great arteries (d-TGA) repaired with the arterial switch operation in early infancy and 29 healthy referent adolescents. We examined whether differences in neurocognitive functioning were related to white matter network topology. We developed mediation models revealing the respective contributions of peri-operative variables and network topology on cognitive outcome. Adolescents with d-TGA had reduced global efficiency at a trend level (p = 0.061), increased modularity (p = 0.012), and increased small-worldness (p = 0.026) as compared to controls. Moreover, these network properties mediated neurocognitive differences between the d-TGA and referent adolescents across every domain assessed. Finally, structural network topology mediated the neuroprotective effect of longer duration of core cooling during reparative neonatal cardiac surgery, as well as the detrimental effects of prolonged hospitalization. Taken together, worse neurocognitive function in adolescents with d-TGA is mediated by global differences in white matter network topology, suggesting that disruption of this configuration of large-scale networks drives neurocognitive dysfunction. These data provide new insights into the interplay between perioperative factors, brain organization, and cognition in patients with complex CHD.