Faculty Bibliography

PURPOSE: To apply the low-rank plus sparse (L+S) matrix decomposition model to reconstruct undersampled dynamic MRI as a superposition of background and dynamic components in various problems of clinical interest. THEORY AND METHODS: The L+S model is natural to represent dynamic MRI data. Incoherence between k-t space (acquisition) and the singular vectors of L and the sparse domain of S is required to reconstruct undersampled data. Incoherence between L and S is required for robust separation of background and dynamic components. Multicoil L+S reconstruction is formulated using a convex optimization approach, where the nuclear norm is used to enforce low rank in L and the l1 norm is used to enforce sparsity in S. Feasibility of the L+S reconstruction was tested in several dynamic MRI experiments with true acceleration, including cardiac perfusion, cardiac cine, time-resolved angiography, and abdominal and breast perfusion using Cartesian and radial sampling. RESULTS: The L+S model increased compressibility of dynamic MRI data and thus enabled high-acceleration factors. The inherent background separation improved background suppression performance compared to conventional data subtraction, which is sensitive to motion. CONCLUSION: The high acceleration and background separation enabled by L+S promises to enhance spatial and temporal resolution and to enable background suppression without the need of subtraction or modeling. Magn Reson Med, 2014. (c) 2014 Wiley Periodicals, Inc.

PURPOSE: Quantitative T2 -relaxation-based contrast has the potential to provide valuable clinical information. Practical T2 -mapping, however, is impaired either by prohibitively long acquisition times or by contamination of fast multiecho protocols by stimulated and indirect echoes. This work presents a novel postprocessing approach aiming to overcome the common penalties associated with multiecho protocols, and enabling rapid and accurate mapping of T2 relaxation values. METHODS: Bloch simulations are used to estimate the actual echo-modulation curve (EMC) in a multi-spin-echo experiment. Simulations are repeated for a range of T2 values and transmit field scales, yielding a database of simulated EMCs, which is then used to identify the T2 value whose EMC most closely matches the experimentally measured data at each voxel. RESULTS: T2 maps of both phantom and in vivo scans were successfully reconstructed, closely matching maps produced from single spin-echo data. Results were consistent over the physiological range of T2 values and across different experimental settings. CONCLUSION: The proposed technique allows accurate T2 mapping in clinically feasible scan times, free of user- and scanner-dependent variations, while providing a comprehensive framework that can be extended to model other parameters (e.g., T1 , B1 + , B0 , diffusion) and support arbitrary acquisition schemes. Magn Reson Med, 2014. (c) 2014 Wiley Periodicals, Inc.

PURPOSE: We used a combined intravoxel incoherent motion-diffusion tensor imaging (IVIM-DTI) methodology to distinguish structural from flow effects on renal diffusion anisotropy. METHODS: Eight volunteers were examined with IVIM-DTI at 3T with 20 diffusion directions and 10 b-values. Mean diffusivity (MD) and fractional anisotropy (FA) from DTI analysis were calculated for low (b 200 s/mm2 ), and full b-value ranges. IVIM-parameters perfusion-fraction fP , pseudo-diffusivity Dp , and tissue-diffusivity Dt were first calculated independently on a voxelwise basis for all directions. After estimating a fixed isotropic fp from these data, global anisotropies of Dt and Dp in the cortex and medulla were determined in a constrained cylindrical description and visualized using polar plots and cosine scatterplots. RESULTS: For all b-value ranges, medullary FA was significantly higher than that of the cortex. The corticomedullary difference was smaller for the high b-value range. Significantly higher fp and Dt were determined for the cortex and showed a significantly higher directional variance in the medulla. Polar plot analysis displayed nearly isotropic Dp and Dt in the cortex and anisotropy in the medulla. CONCLUSION: Both flow and microstructure apparently contribute to the medullary diffusion anisotropy. The described novel method may be useful in separating decreased tubular flow from irreversible structural tubular damage, for example, in diabetic nephropathy or during allograft rejection. Magn Reson Med, 2014. (c) 2014 Wiley Periodicals, Inc.

Complex and precisely orchestrated genetic programs contribute to the generation, migration, and maturation of cortical GABAergic interneurons (cIN). Yet, little is known about the signals that mediate the rapid alterations in gene expression that are required for cINs to transit through a series of developmental steps leading to their mature properties in the cortex. Here, we investigated the function of post-transcriptional regulation of gene expression by microRNAs on the development of cIN precursors. We find that conditional removal of the RNAseIII enzyme Dicer reduces the number of cINs in the adult mouse. Dicer is further necessary for the morphological and molecular maturation of cINs. Loss of mature miRNAs affects cINs development by impairing migration and differentiation of this cell type, while leaving proliferation of progenitors unperturbed. These developmental defects closely matched the abnormal expression of molecules involved in apoptosis and neuronal specification. In addition, we identified several miRNAs that are selectively upregulated in the postmitotic cINs, consistent with a role of miRNAs in the post-transcriptional control of the differentiation and apoptotic programs essential for cIN maturation. Thus, our results indicate that cIN progenitors require Dicer-dependent mechanisms to fine-tune the migration and maturation of cINs.

Diffusional kurtosis imaging (DKI) is extended to double-pulsed-field-gradient (d-PFG) diffusion MRI sequences. This gives a practical approach for acquiring and analyzing d-PFG data. In particular, the leading d-PFG effects, beyond what conventional single-pulsed field gradient (s-PFG) provides, are interpreted in terms of the kurtosis for a diffusion displacement probability density function (dPDF) in a six-dimensional (6D) space. The 6D diffusional kurtosis encodes the unique information provided by d-PFG sequences up to second order in the b-value. This observation leads to a compact expression for the signal magnitude, and it suggests novel data acquisition and analysis methods. Double-pulsed DKI (DP-DKI) is demonstrated for in vivo mouse brain with d-PFG data obtained at 7 T. Copyright © 2014 John Wiley & Sons, Ltd.

The cellular diversity of interneurons in the neocortex is thought to reflect subtype-specific roles of cortical inhibition. Here we ask whether perturbations to two subtypes--parvalbumin-positive (PV+) and somatostatin-positive (SST+) interneurons--can be compensated for with respect to their contributions to cortical development. We use a genetic cell fate switch to delete both PV+ and SST+ interneurons selectively in cortical layers 2-4 without numerically changing the total interneuron population. This manipulation is compensated for at the level of synaptic currents and receptive fields (RFs) in the somatosensory cortex. By contrast, we identify a deficit in inhibitory synchronization in vitro and a large reduction in cortical gamma oscillations in vivo. This reveals that, while the roles of inhibition in establishing cortical inhibitory/excitatory balance and RFs can be subserved by multiple interneuron subtypes, gamma oscillations depend on cellular properties that cannot be compensated for--likely, the fast signalling properties of PV+ interneurons.

Obesity is a major epidemic in many parts of the world. One of the main factors contributing to obesity is overconsumption of high-fat and high-calorie food, which is driven by the rewarding properties of these types of food. Previous studies have suggested that dysfunction in reward circuits may be associated with overeating and obesity. The nature of this dysfunction, however, is still unknown. Here, we demonstrate impairment in reward-based associative learning specific to food in obese women. Normal-weight and obese participants performed an appetitive reversal learning task in which they had to learn and modify cue-reward associations. To test whether any learning deficits were specific to food reward or were more general, we used a between-subject design in which half of the participants received food reward and the other half received money reward. Our results reveal a marked difference in associative learning between normal-weight and obese women when food was used as reward. Importantly, no learning deficits were observed with money reward. Multiple regression analyses also established a robust negative association between body mass index and learning performance in the food domain in female participants. Interestingly, such impairment was not observed in obese men. These findings suggest that obesity may be linked to impaired reward-based associative learning and that this impairment may be specific to the food domain.