Faculty Bibliography

OBJECTIVE: Generalized anxiety disorder (GAD) typically begins during adolescence and can persist into adulthood. The pathophysiological mechanisms underlying this disorder remain unclear. Recent evidence from resting state functional magnetic resonance imaging (R-fMRI) studies in adults suggests disruptions in amygdala-based circuitry; the present study examines this issue in adolescents with GAD. METHOD: Resting state fMRI scans were obtained from 15 adolescents with GAD and 20 adolescents without anxiety who were group matched on age, sex, scanner, and intelligence. Functional connectivity of the centromedial, basolateral, and superficial amygdala subdivisions was compared between groups. We also assessed the relationship between amygdala network dysfunction and anxiety severity. RESULTS: Adolescents with GAD exhibited disruptions in amygdala-based intrinsic functional connectivity networks that included regions in medial prefrontal cortex, insula, and cerebellum. Positive correlations between anxiety severity scores and amygdala functional connectivity with insula and superior temporal gyrus were also observed within the GAD group. There was some evidence of greater overlap (less differentiation of connectivity patterns) of the right basolateral and centromedial amygdala networks in the adolescents with, relative to those without, GAD. CONCLUSIONS: These findings suggest that adolescents with GAD manifest alterations in amygdala circuits involved in emotion processing, similar to findings in adults. In addition, disruptions were observed in amygdala-based networks involved in fear processing and the coding of interoceptive states.

OBJECTIVES: The aim of this study was to assess the impact of oral water and intravenous furosemide challenges on blood oxygenation level-dependent magnetic resonance imaging measurements in the kidney and to examine the contribution of R2 (=1/T2) to changes in R2* (=1/T2*). MATERIALS AND METHODS: This Health Insurance Portability and Accountability Act-compliant study had institutional review board approval, and written informed consent was obtained from all subjects. Nine healthy volunteers were imaged at 3 T on 2 visits. During each visit, a baseline fasting magnetic resonance acquisition was followed by a diuretic challenge: oral water load for the first visit and furosemide for the second. R2* and R2 values in the renal cortex and medulla were measured using multiple gradient echo and multiple spin echo sequences, respectively, and R2' values were computed as R2' = R2* - R2. Timed urinary output was also measured. RESULTS: Averaged across all subjects, the R2* response to furosemide was greater than to water and greater in the medulla than the cortex. The mean R2 responses exhibited the same trends but were uniformly smaller than the mean R2* responses. The peak changes in R2* and R2 appeared, on average, 10 to 14 minutes before peak urinary output. The median percentage contribution of R2 to R2* changes was 16% in the medulla after both challenges. In the cortex, the median contribution was 48% after water load and 58% after furosemide challenge. CONCLUSIONS: The contributions of R2 to R2* changes after water load and furosemide challenge are not negligible, especially in the renal cortex. In routine clinical practice, R2* could be used alone as a rough surrogate for R2' in the medulla. However, in the cortex, both R2 and R2* should be measured to obtain accurate values of R2'.

We propose and demonstrate a full 3D longitudinal Hadamard spectroscopic imaging scheme for obtaining chemical shift maps, using adiabatic inversion pulses to encode the spins' positions. The approach offers several advantages over conventional Fourier-based encoding methods, including a localized point spread function; no aliasing, allowing for volumes of interest smaller than the object being imaged; an option for acquiring noncontiguous voxels; and inherent outer volume rejection. The latter allows for doing away with conventional outer volume suppression schemes, such as point resolved spectroscopy (PRESS) and stimulated echo acquisition mode (STEAM), and acquiring non-spin-echo spectra with short acquisition delay times, limited only by the excitation pulse's duration. This, in turn, minimizes T(2) decay, maximizes the signal-to-noise ratio, and reduces J-coupling induced signal decay. Results are presented for both a phantom and an in vivo healthy volunteer at 3 T. Magn Reson Med, 2012. (c) 2012 Wiley Periodicals, Inc.

There are no established biomarkers for mild traumatic brain injury (mTBI), in part because post-concussive symptoms (PCS) are subjective and conventional imaging is typically unremarkable. To test whether diffuse axonal abnormalities quantified with three-dimensional (3D) proton magnetic resonance spectroscopic imaging (1H-MRSI) correlated with patients' PCS, we retrospectively studied 26 mTBI patients (mean Glasgow Coma Scale score of 14.7), 18-56 years old, 3 - 55 days post injury and 13 controls. All were scanned at 3 Tesla with T1-and T2-weighted MRI and 3D 1H-MRSI (480 voxels over 360 cm3, ~30% of the brain). On scan day patients completed a symptom questionnaire and those indicating at least one of the most common acute/subacute mTBI symptoms (headache, dizziness, sleep disturbance, memory deficits, blurred vision) were grouped as PCS-positive. Global gray- and white matter (GM/WM) absolute concentrations of N-acetylaspartate (NAA), choline (Cho), creatine (Cr) and myo-inositol (mI) in the PCS-positive and PCS-negative patients were compared to age- and gender-matched controls using two-way analysis of variance. The results showed that the PCS-negative group (n=11) and controls (n=8) did not differ in any GM or WM metabolite level. The PCS-positive patients (n=15), however, had lower WM NAA than the controls (n=12): 7.0+/-0.6 mM (mean+/- standard deviation) versus 7.9+/-0.5mM (p=0.0007). Global WM NAA, therefore, showed sensitivity to the TBI sequelae associated with common PCS in individuals with mostly normal neuroimaging as well as GCS scores. This suggests a potential biomarker role in a patient population in which objective measures of injury and symptomatology are currently lacking.

To test the hypotheses that global decreased neuro-axonal integrity reflected by decreased N-acetylaspartate (NAA) and increased glial activation reflected by an elevation in its marker, the myo-inositol (mI), present in a CD8-depleted rhesus macaque model of HIV-associated neurocognitive disorders. To this end, we performed quantitative MRI and 16 x 16 x 4 multivoxel proton MRS imaging (TE/TR = 33/1400 ms) in five macaques pre- and 4-6 weeks post-simian immunodeficiency virus infection. Absolute NAA, creatine, choline (Cho), and mI concentrations, gray and white matter (GM and WM) and cerebrospinal fluid fractions were obtained. Global GM and WM concentrations were estimated from 224 voxels (at 0.125 cm(3) spatial resolution over ~35% of the brain) using linear regression. Pre- to post-infection global WM NAA declined 8%: 6.6 +/- 0.4 to 6.0 +/- 0.5 mM (p = 0.05); GM Cho declined 20%: 1.3 +/- 0.2 to 1.0 +/- 0.1 mM (p < 0.003); global mI increased 11%: 5.7 +/- 0.4 to 6.5 +/- 0.5 mM (p < 0.03). Global GM and WM brain volume fraction changes were statistically insignificant. These metabolic changes are consistent with global WM (axonal) injury and glial activation, and suggest a possible GM host immune response

A non-spin-echo multivoxel proton MR localization method based on three-dimensional transverse Hadamard spectroscopic imaging is introduced and demonstrated in a phantom and the human brain. Spatial encoding is achieved with three selective 90 degrees radiofrequency pulses along perpendicular axes: The first two create a longitudinal +/-M(Z) Hadamard order in the volume of interest. The third pulse spatially Hadamard-encodes the +/-M(Z) s in the volume of interest in the third direction while bringing them to the transverse plane to be acquired immediately. The approaching-ideal point spread function of Hadamard encoding and very short acquisition delay yield signal-to-noise-ratios of 20 +/- 8, 23 +/- 9, and 31 +/- 10 for choline, creatine, and N-acetylaspartate in the human brain at 1.5 T from 1 cm(3) voxels in 21 min. The advantages of transverse Hadamard spectroscopic imaging are that unlike gradient (Fourier) phase-encoding: (i) the volume of interest does not need to be smaller than the field of view to prevent aliasing; (ii) the number of partitions in each direction can be small, 8, 4, or even 2 at no cost in point spread function; (iii) the volume of interest does not have to be contiguous; and (iv) the voxel profile depends on the available B(1) and pulse synthesis paradigm and can, therefore, at least theoretically, approach "ideal" "1" inside and "0" elsewhere. Magn Reson Med, 2012. (c) 2012 Wiley Periodicals, Inc.

MPS encompasses a group of rare lysosomal storage disorders that are associated with the accumulation of glycosaminoglycans (GAG) in organs and tissues. This accumulation can lead to the progressive development of a variety of clinical manifestations. Ear, nose, throat (ENT) and respiratory problems are very common in patients with MPS and are often among the first symptoms to appear. Typical features of MPS include upper and lower airway obstruction and restrictive pulmonary disease, which can lead to chronic rhinosinusitis or chronic ear infections, recurrent upper and lower respiratory tract infections, obstructive sleep apnoea, impaired exercise tolerance, and respiratory failure. This review provides a detailed overview of the ENT and respiratory manifestations that can occur in patients with MPS and discusses the issues related to their evaluation and management.