Faculty Bibliography

OBJECTIVE:: As approximately 40% of persons with HIV also suffer neurocognitive decline, we sought to assess metabolic dysfunction in the brains of simian immunodeficiency virus (SIV)-infected rhesus macaques, an advanced animal model, in structures involved in cognitive function. We test the hypothesis that SIV-infection produces proton-magnetic resonance spectroscopic imaging (H-MRSI)-observed decline in the neuronal marker, N-acetylaspartate (NAA), and elevations in the glial marker, myo-inositol (mI), and associated creatine (Cr) and choline (Cho) in these structures. DESIGN:: Pre- and 4-6 weeks post-SIV infection (with CD8 T-lymphocyte depletion) was monitored with T2-weighted quantitative MRI and 16 x 16 x 4 multivoxel H-MRSI (TE/TR = 33/1400 ms) in the brains of five rhesus macaques. METHODS:: Exploiting the high-resolution H-MRSI grid, we obtained absolute, cerebrospinal fluid partial volume-corrected NAA, Cr, Cho and mI concentrations from centrum semiovale, caudate nucleus, putamen, thalamus and hippocampus regions. RESULTS:: Pre- to post-infection mean Cr increased in the thalamus: 7.2 +/- 0.4 to 8.0 +/- 0.8 mmol/l (+11%, P < 0.05); mI increased in the centrum semiovale: 5.1 +/- 0.8 to 6.6 +/- 0.8 mmol/l, caudate: 5.7 +/- 0.7 to 7.3 +/- 0.5 mmol/l, thalamus: 6.8 +/- 0.8 to 8.5 +/- 0.8 mmol/l and hippocampus: 7.7 +/- 1.2 to 9.9 +/- 0.4 mmol/l (+29%, +27%, +24% and +29%, all P < 0.05). NAA and Cho changes were not significant. CONCLUSION:: SIV-infection appears to cause brain injury indirectly, through glial activation, while the deep gray matter structures' neuronal cell bodies are relatively spared. Treatment regimens to reduce gliosis may, therefore, prevent neuronal damage and its associated neurocognitive impairment.

PURPOSE: To analyze the effect of B0 field drift on multivoxel MR spectroscopic imaging and to propose an approach for its correction. THEORY AND METHODS: It is shown, both theoretically and in a phantom, that for approximately 30 min acquisitions a linear B0 drift ( approximately 0.1 ppm/h) will cause localization errors that can reach several voxels (centimeters) in the slower varying phase encoding directions. An efficient and unbiased estimator is proposed for tracking the drift by interleaving short ( approximately T2*), nonlocalized acquisitions on the nonsuppressed water each pulse repetition time, as shown in 10 volunteers at 1.5 and 3 T. RESULTS: The drift is shown to be predominantly linear in both the phantom and volunteers at both fields. The localization errors are observed and quantified in both phantom and volunteers. The unbiased estimator is shown to reliably track the instantaneous frequency in vivo despite only using a small portion of the FID. CONCLUSION: Contrary to single-voxel MR spectroscopy, where it leads to line broadening, field drift can lead to localization errors in the longer chemical shift imaging experiments. Fortunately, this drift can be obtained at a negligible cost to sequence timing, and corrected for in post processing.

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.

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.

PURPOSE: The hippocampus is central to the pathophysiology of schizophrenia. Histology shows abnormalities in the dentate granule cell layer (DGCL), but its small size (~100mum thickness) has precluded in vivo human studies. We used ultra high field magnetic resonance imaging (MRI) to compare DGCL morphology of schizophrenic patients to matched controls. METHOD: Bilateral hippocampi of 16 schizophrenia patients (10 male) 40.7+/-10.6years old (mean+/-standard deviation) were imaged at 7Tesla MRI with heavily T2()-weighted gradient-echo sequence at 232mum in-plane resolution (0.08muL image voxels). Fifteen matched controls (8 male, 35.6+/-9.4years old) and one ex vivo post mortem hippocampus (that also underwent histopathology) were scanned with same protocol. Three blinded neuroradiologists rated each DGCL on a qualitative scale of 1 to 6 (from "not discernible" to "easily visible, appearing dark gray or black") and mean left and right DGCL scores were compared using a non-parametric Mann-Whitney test. RESULTS: MRI identification of the DGCL was validated with histopathology. Mean right and left DGCL ratings in patients (3.2+/-1.0 and 3.5+/-1.2) were not statistically different from those of controls (3.9+/-1.1 and 3.8+/-0.8), but patients had a trend for lower right DGCL score (p=0.07), which was significantly associated with patient diagnosis (p=0.05). The optimal 48% sensitivity and 80% specificity for schizophrenia were achieved with a DGCL rating of