Faculty Bibliography

PURPOSE: To design a proton MR spectroscopy (1 H-MRS) localization sequence that combines the signal-to-noise-ratio (SNR) benefits of point resolved spectroscopy (PRESS) with the high pulse bandwidths, low chemical shift displacements (CSD), low specific absorption rates (SAR), short echo times (TE), and superior radiofrequency transmit field (B1+ ) immunity of stimulated echo acquisition mode (STEAM), by simultaneously refocusing and acquiring both the double-spin and stimulated echo coherence pathways from the volume of interest. THEORY AND METHODS: We propose a family of 1 H-MRS sequences comprising three orthogonal spatially selective pulses with flip angles 90 degrees < alpha, beta, gamma < 128 degrees . The stimulated and double-spin echo are refocused in-phase simultaneously by altering the pulses' phases, flip angles and timing, as well as the interpulse gradient spoiling moments. The approximately 90 degrees nutations of alpha, beta, gamma provide STEAM-like advantages (lower SAR, in-plane CSD and TE; greater B1+ immunity), but with SNRs comparable with PRESS. RESULTS: Phantom and in vivo brain experiments show that 83-100% of the PRESS SNR (metabolite-dependent) is achieved at under 75% of the SAR and 66% lower in-plane CSD. CONCLUSION: The advantages of STEAM can be augmented with the higher SNR of PRESS by combining the spin and stimulated echoes. Quantification, especially of J-coupled resonances and intermediate and long TEs, must be carefully considered. Magn Reson Med, 2014. (c) 2014 Wiley Periodicals, Inc.

Concentration of the neuronal marker, N-acetylaspartate (NAA), a quantitative metric for the health and density of neurons, is currently obtained by integration of the manually defined peak in whole-head proton (1 H)-MRS. Our goal was to develop a full spectral modeling approach for the automatic estimation of the whole-brain NAA concentration (WBNAA) and to compare the performance of this approach with a manual frequency-range peak integration approach previously employed. MRI and whole-head 1 H-MRS from 18 healthy young adults were examined. Non-localized, whole-head 1 H-MRS obtained at 3 T yielded the NAA peak area through both manually defined frequency-range integration and the new, full spectral simulation. The NAA peak area was converted into an absolute amount with phantom replacement and normalized for brain volume (segmented from T1 -weighted MRI) to yield WBNAA. A paired-sample t test was used to compare the means of the WBNAA paradigms and a likelihood ratio test used to compare their coefficients of variation. While the between-subject WBNAA means were nearly identical (12.8 +/- 2.5 mm for integration, 12.8 +/- 1.4 mm for spectral modeling), the latter's standard deviation was significantly smaller (by ~50%, p = 0.026). The within-subject variability was 11.7% (+/-1.3 mm) for integration versus 7.0% (+/-0.8 mm) for spectral modeling, i.e., a 40% improvement. The (quantifiable) quality of the modeling approach was high, as reflected by Cramer-Rao lower bounds below 0.1% and vanishingly small (experimental - fitted) residuals. Modeling of the whole-head 1 H-MRS increases WBNAA quantification reliability by reducing its variability, its susceptibility to operator bias and baseline roll, and by providing quality-control feedback. Together, these enhance the usefulness of the technique for monitoring the diffuse progression and treatment response of neurological disorders

PURPOSE: To reduce the specific-absorption-rate (SAR) and chemical shift displacement (CSD) of three-dimensional (3D) Hadamard spectroscopic imaging (HSI) and maintain its point spread function (PSF) benefits. METHODS: A 3D hybrid of 2D longitudinal, 1D transverse HSI (L-HSI, T-HSI) sequence is introduced and demonstrated in a phantom and the human brain at 3 Tesla (T). Instead of superimposing each of the selective Hadamard radiofrequency (RF) pulses with its N single-slice components, they are cascaded in time, allowing N-fold stronger gradients, reducing the CSD. A spatially refocusing 180 degrees RF pulse following the T-HSI encoding block provides variable, arbitrary echo time (TE) to eliminate undesirable short T2 species' signals, e.g., lipids. RESULTS: The sequence yields 10-15% better signal-to-noise ratio (SNR) and 8-16% less signal bleed than 3D chemical shift imaging of equal repetition time, spatial resolution and grid size. The 13 +/- 6, 22 +/- 7, 24 +/- 8, and 31 +/- 14 in vivo SNRs for myo-inositol, choline, creatine, and N-acetylaspartate were obtained in 21 min from 1 cm3 voxels at TE approximately 20 ms. Maximum CSD was 0.3 mm/ppm in each direction. CONCLUSION: The new hybrid HSI sequence offers a better localized PSF at reduced CSD and SAR at 3T. The short and variable TE permits acquisition of short T2 and J-coupled metabolites with higher SNR. Magn Reson Med, 2013. (c) 2013 Wiley Periodicals, Inc.

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.

Since approximately 5-10% of the ~50,000 tuberous sclerosis complex (TSC) patients in the US are "MRI-negative," our goal was to test the hypothesis that they nevertheless exhibit metabolic abnormalities. To test this, we used proton MR spectroscopy to obtain and compare gray and white matter (GM and WM) levels of the neuronal marker, N-acetylaspartate (NAA), the glial marker, myo-inositol (mI), and its associated creatine (Cr), and choline (Cho) between two "MRI-negative" female TSC patients (ages 5 and 43 years) and their matched controls. The NAA, Cr, Cho and mI concentrations, 9.8, 6.3, 1.4, and 5.7mM, in the pediatric control were similar to those of the patients, whereas the adult patient revealed a 17% WM NAA decrease and 16% WM Cho increase from their published means for healthy adults - both outside their respective 90% prediction intervals. These findings suggest that longer disease duration and/or TSC2 gene mutation may cause axonal dysfunction and demyelination.

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.