Faculty Bibliography

Severe temper outbursts (STO) in children are associated with impaired school and family functioning and may contribute to negative outcomes. These outbursts can be conceptualized as excessive frustration responses reflecting reduced emotion regulation capacity. The anterior cingulate cortex (ACC) has been implicated in negative affect as well as emotional control, and exhibits disrupted function in children with elevated irritability and outbursts. This study examined the intrinsic functional connectivity (iFC) of a region of the ACC, the anterior midcingulate cortex (aMCC), in 5- to 9-year-old children with STO (n = 20), comparing them to children with attention-deficit/hyperactivity disorder (ADHD) without outbursts (ADHD; n = 18). Additional analyses compared results to a sample of healthy children (HC; n = 18) and examined specific associations with behavioral and emotional dysregulation. Compared to the ADHD group, STO children exhibited reduced iFC between the aMCC and surrounding regions of the ACC, and increased iFC between the aMCC and precuneus. These differences were also seen between the STO and HC groups; ADHD and HC groups did not differ. Specificity analyses found associations between aMCC-ACC connectivity and hyperactivity, and between aMCC-precuneus iFC and emotion dysregulation. Disruption in aMCC networks may underlie the behavioral and emotional dysregulation characteristic of children with STO.

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PURPOSE: Previous work with body-size objects suggested that loops are optimal MR detectors at low fields, whereas electric dipoles are required to maximize signal-to-noise ratio (SNR) at ultrahigh fields ( >/= 7 T). Here we investigated how many loops and/or dipoles are needed to approach the ultimate intrinsic SNR (UISNR) at various field strengths. METHODS: We calculated the UISNR inside dielectric cylinders mimicking different anatomical regions. We assessed the performance of various arrays with respect to the UISNR. We validated our results by comparing simulated and experimental coil performance maps. RESULTS: Arrays with an increasing number of loops can rapidly approach the UISNR at fields up to 3 T, but are suboptimal at ultrahigh fields for body-size objects. The opposite is true for dipole arrays. At 7 T and above, 16 dipoles provide considerably larger central SNR than any possible loop array, and minimal g factor penalty for parallel imaging. CONCLUSIONS: Electric dipoles can be advantageous at ultrahigh fields because they can produce both curl-free and divergence-free currents, whereas loops are limited to divergence-free contributions only. Combining loops and dipoles may be optimal for body imaging at 3 T, whereas arrays of loops or dipoles alone may perform better at lower or higher field strengths, respectively. Magn Reson Med, 2017. (c) 2017 International Society for Magnetic Resonance in Medicine.

BACKGROUND: Diffusion tensor imaging studies have shown atypical fractional anisotropy (FA) in individuals with attention-deficit/hyperactivity disorder (ADHD), albeit with conflicting results. We performed meta-analyses of whole-brain voxel-based analyses (WBVBA) and tract-based spatial statistics (TBSS) studies in ADHD, along with a qualitative review of TBSS studies addressing the issue of head motion, which may bias results. METHODS: We conducted a systematic literature search (last search on April 1st, 2016) to identify studies comparing FA values between individuals with ADHD and typically developing (TD) participants. Signed differential mapping was used to compute effect sizes and integrate WBVBA and TBSS studies, respectively. TBSS datasets reporting no between-group motion differences were identified. RESULTS: We identified 14 WBVBA (ADHDn = 314, TDn = 278) and 13 TBSS datasets (ADHDn = 557, TDn = 568). WBVBA meta-analysis showed both significantly lower and higher FA values in individuals with ADHD; TBSS meta-analysis showed significantly lower FA in ADHD compared with TD in four clusters: two in the corpus callosum (isthmus and posterior midbody), one in right inferior fronto-occipital fasciculus, and one in left inferior longitudinal fasciculus. However, four of six datasets confirming no group-differences in motion showed no significant between-group FA differences. CONCLUSIONS: A growing diffusion tensor imaging (DTI) literature (total N = 1,717) and a plethora of apparent findings suggest atypical interhemispheric connection in ADHD. However, FA results in ADHD should be considered with caution, since many studies did not examine potential group differences in head motion, and most of the studies reporting no difference in motion showed no significant results. Future studies should address head motion as a priority and assure that groups do not differ in head motion.

PURPOSE: To describe a new bench measurement based on quality (Q) factors to estimate the coil noise relative to the sample noise of dipole antennas at 7 T. METHODS: Placing a dipole antenna close to a highly conductive sample surrogate (HCSS) greatly reduces radiation loss, and using QHCSS gives a more accurate estimate of coil resistance than Qunloaded . Instead of using the ratio of unloaded and sample-loaded Q factors, the ratio of HCSS-loaded and sample-loaded Q factors should be used at ultra-high fields. A series of simulations were carried out to analyze the power budget of sample-loaded or HCSS-loaded dipole antennas. Two prototype dipole antennas were also constructed for bench measurements to validate the simulations. RESULTS: Simulations showed that radiation loss was suppressed when the dipole antenna was HCSS-loaded, and coil loss was largely the same as when the dipole was loaded by the sample. Bench measurements also showed good alignment with simulations. CONCLUSIONS: Using the ratio QHCSS /Qloaded gives a good estimate of the coil loss for dipole antennas at 7 T, and provides a convenient bench measurement to predict the body noise dominance of dipole antenna designs. The new approach also applies to conventional surface loop coils at ultra-high fields. Magn Reson Med 2017. (c) 2017 International Society for Magnetic Resonance in Medicine.

PURPOSE: A 5D whole-heart sparse imaging framework is proposed for simultaneous assessment of myocardial function and high-resolution cardiac and respiratory motion-resolved whole-heart anatomy in a single continuous noncontrast MR scan. METHODS: A non-electrocardiograph (ECG)-triggered 3D golden-angle radial balanced steady-state free precession sequence was used for data acquisition. The acquired 3D k-space data were sorted into a 5D dataset containing separated cardiac and respiratory dimensions using a self-extracted respiratory motion signal and a recorded ECG signal. Images were then reconstructed using XD-GRASP, a multidimensional compressed sensing technique exploiting correlations/sparsity along cardiac and respiratory dimensions. 5D whole-heart imaging was compared with respiratory motion-corrected 3D and 4D whole-heart imaging in nine volunteers for evaluation of the myocardium, great vessels, and coronary arteries. It was also compared with breath-held, ECG-gated 2D cardiac cine imaging for validation of cardiac function quantification. RESULTS: 5D whole-heart images received systematic higher quality scores in the myocardium, great vessels and coronary arteries. Quantitative coronary sharpness and length were always better for the 5D images. Good agreement was obtained for quantification of cardiac function compared with 2D cine imaging. CONCLUSION: 5D whole-heart sparse imaging represents a robust and promising framework for simplified comprehensive cardiac MRI without the need for breath-hold and motion correction. Magn Reson Med, 2017. (c) 2017 International Society for Magnetic Resonance in Medicine.

PURPOSE: The proposed reconstruction framework addresses the reconstruction accuracy, noise propagation and computation time for magnetic resonance fingerprinting. METHODS: Based on a singular value decomposition of the signal evolution, magnetic resonance fingerprinting is formulated as a low rank (LR) inverse problem in which one image is reconstructed for each singular value under consideration. This LR approximation of the signal evolution reduces the computational burden by reducing the number of Fourier transformations. Also, the LR approximation improves the conditioning of the problem, which is further improved by extending the LR inverse problem to an augmented Lagrangian that is solved by the alternating direction method of multipliers. The root mean square error and the noise propagation are analyzed in simulations. For verification, in vivo examples are provided. RESULTS: The proposed LR alternating direction method of multipliers approach shows a reduced root mean square error compared to the original fingerprinting reconstruction, to a LR approximation alone and to an alternating direction method of multipliers approach without a LR approximation. Incorporating sensitivity encoding allows for further artifact reduction. CONCLUSION: The proposed reconstruction provides robust convergence, reduced computational burden and improved image quality compared to other magnetic resonance fingerprinting reconstruction approaches evaluated in this study. Magn Reson Med, 2017. (c) 2017 International Society for Magnetic Resonance in Medicine.

Anti-PD-1 and anti-PD-L1 immunotherapy has provided a new therapeutic opportunity for treatment of advanced-stage non-small cell lung cancer (NSCLC). However, overall objective response rates are approximately 15%-25% in all NSCLC patients who receive anti-PD therapy. Therefore, strategies to overcome primary resistance to anti-PD immunotherapy are urgently needed. We hypothesized that the barrier to the success of anti-PD therapy in most NSCLC patients can be overcome by stimulating the lymphocyte infiltration at cancer sites through locoregional virotherapy. To this end, in this study, we determined combination effects of anti-PD immunotherapy and oncolytic adenoviral vector-mediated tumor necrosis factor-α-related apoptosis-inducing ligand (TRAIL) gene therapy (Ad/E1-TRAIL) or adenoviral-mediated TP53 (Ad/CMV-TP53) gene therapy in syngeneic mice bearing subcutaneous tumors derived from M109 lung cancer cells. Both anti-PD-1 and anti-PD-L1 antibodies failed to elicit obvious therapeutic effects in the M109 tumors. Intratumoral administration of Ad/E1-TRAIL or Ad/CMV-TP53 alone suppressed tumor growth in animals preexposed to an adenovector and bearing subcutaneous tumors derived from M109 cells. However, combining either anti-PD-1 or anti-PD-L1 antibody with these two adenoviral vectors elicited the strongest anticancer activity in mice with existing immunity to adenoviral vectors. Dramatically enhanced intratumoral immune response was detected in this group of combination therapy based on infiltrations of CD4+ and CD8+ lymphocytes and macrophages in tumors. Our results demonstrate that resistance to anti-PD-1 immunotherapy in syngeneic mouse lung cancer can be overcome by locoregional virotherapy.