Faculty Bibliography

Purpose: Despite the extensive opportunities offered by current state-of-the-art PET-MR systems [1], their use is still far from routine clinical practice. While it is feasible to acquire PET data from a single bed position in about 5 minutes, collecting the clinically relevant variety of traditional MR contrasts requires substantially more time. This bottleneck formed by the traditional MR paradigm leads to a relatively inefficient use of the PET component and is particularly prohibitive for multiplebed-position PET protocols. This work proposes a one-step procedure that merges the MR fingerprinting (MRF) framework [2] with the PET acquisition, and employs a dedicated multi-modality reconstruction exploiting joint information among multiple contrast weightings to enable a 6 minute comprehensive PET-MR exam, which can provide the majority of clinical MR contrasts alongside quantitative parametric maps of the relaxation parameters (T1, T2) together with improved PET images. Theory & Methods: Although MRF is inherently robust against incoherent undersampling artifacts, there is a limit beyond which the final image quality will suffer. Instead of relaying purely on incoherence between undersampling artifacts and simulated signal evolutions (standard MRF reconstruction), we propose an extension of a recently proposed nonlinear joint multimodality reconstruction [3] to simultaneously reconstruct the series of MRF images and the PET image by enforcing joint sparsity, thereby reducing residual undersampling artifacts in MR while at the same time improving PET reconstruction quality. The joint MRF-PET reconstruction is performed by minimizing the …

We have recently extended conventional single-pulsed-field-gradient (s-PFG) diffusional kurtosis imaging (DKI) to double-pulsed-field-gradient (d-PFG) diffusion MRI sequences, with a method known as double-pulsed DKI (DP-DKI). By virtue of a six-dimensional (6D) formulation for q-space, many of the results and insights of s-PFG DKI are generalized to those of DP-DKI. Owing to the fact that DP-DKI isolates the second order contributions to the d-PFG signal (i.e. second order in b-value), the 6D diffusional kurtosis encodes information beyond what is available from s-PFG sequences. Previously, we have demonstrated DP-DKI for in vivo mouse brain at 7 T, and it is the objective of this study to demonstrate the feasibility of DP-DKI at 3 T for the in vivo assessment of human brain microstructure. In addition, an example is given of how to utilize the additional information obtained from DP-DKI for the purpose of biophysical modeling. The relationship between a specific microscopic anisotropy metric estimated from DP-DKI and other recently proposed measures is also discussed.

A fundamental theoretical result for diffusion MRI is the formula by Stejskal showing that the diffusion NMR signal is proportional to the Fourier transform of the diffusion displacement probability density function. Here this result is extended to multiple-pulsed diffusion MRI (MP-dMRI) by using a higher dimensional q-space formalism to express the diffusion-weighted signal for a sequence with N diffusion wave vectors in terms of a Fourier transform of a diffusion displacement probability density function in a 3N-dimensional space. As an illustration of the application of this extended version of Stejskal's formula, it is used to analyze the cumulant expansion of the signal magnitude for MP-dMRI.

Organisms react to environmental challenges by activating a coordinated set of brain-body responses known as the stress response. These physiological and behavioral countermeasures are, in large part, regulated by the neuroendocrine hypothalamic-pituitary-adrenal (HPA) axis. Normal functioning of the HPA axis ensures that an organism responds appropriately to altered environmental demands, representing an essential system to promote survival. Over the past several decades, increasing evidence supports the hypothesis that disruption of the HPA axis can lead to dysregulated stress response phenotypes, exacting a physiological cost on the organism commonly referred to as allostatic load. Furthermore, it has been recognized that high allostatic load can contribute to increased vulnerability of the organism to further challenges. This observation leads to the notion that disrupted HPA function and resulting inappropriate responses to stressors may underlie many neuropsychiatric disorders, including depression and anxiety. In the present set of studies, we investigate the role of both the normally functioning and disrupted HPA axis in the endocrine, neural, and behavioral responses to acute stress. Using a model of non-invasive chronic corticosterone treatment in mice, we show that dysregulating the normal function of the HPA leads to a mismatch between the hormonal and neural response to acute stress, resulting in abnormal behavioral coping strategies. We believe this model can be leveraged to tease apart the mechanisms by which altered HPA function contributes to neurobehavioral dysregulation in response to acute stress.

Decision-making studies have implicated the ventromedial prefrontal cortex (vmPFC) in tracking the value of rewards and punishments. At the same time, fear-learning studies have pointed to a role of the same area in updating previously learned cue-outcome associations. To disentangle these accounts, we used a reward reversal-learning paradigm in a functional magnetic resonance imaging study in 18 human participants. Participants first learned that one of two colored squares (color A) was associated with monetary reward, whereas the other (color B) was not, and then had to learn that these contingencies reversed. Consistent with value representation, activity of a dorsal region of vmPFC was positively correlated with reward magnitude. Conversely, a more ventral region of vmPFC responded more to color A than to color B after contingency reversal, compatible with a role of inhibiting the previously learned response that was no longer appropriate. Moreover, the response strength was correlated with subjects' behavioral learning strength. Our findings provide direct evidence for the spatial dissociation of value representation and affective response inhibition in the vmPFC.

In behavioral economics, the "endowment effect" describes the robust finding that prices people are willing to accept (WTA) for a good exceed prices people are willing to pay (WTP) for the same good. The increase in WTA values is often explained by the sellers' negative hedonic response to losing their item. Recent studies, however, show that subtle cues may change participants' perspective, influencing their valuations. We hypothesized that implicit connotations of instructional language may be one of those cues. To test this hypothesis we manipulated the wording of instructions in two conditions: in the Sell condition, subjects were endowed with a set of pens and asked to select an amount of money for which they would sell the pens back and in the Take condition, subjects were endowed with the pens and asked to select an amount of money they would take for the pens. Participants in each condition also estimated the market value of the pens. Consistent with our hypothesis, WTA in the Sell condition was higher than in the Take condition, though there were no differences in market values between conditions. These findings show that instructional language does influence participant valuations. Furthermore, we suggest that those being asked to "sell" use their market estimations as the salient reference point in the transaction.