Faculty Bibliography

Temperature is a hallmark parameter influencing almost all magnetic resonance properties (e.g., T₁ , T₂ , proton density, and diffusion). In the preclinical setting, temperature has a large influence on animal physiology (e.g., respiration rate, heart rate, metabolism, and oxidative stress) and needs to be carefully regulated, especially when the animal is under anesthesia and thermoregulation is disrupted. We present an open-source heating and cooling system capable of regulating the temperature of the animal. The system was designed using Peltier modules capable of heating or cooling a circulating water bath with active temperature feedback. Feedback was obtained using a commercial thermistor, placed in the animal rectum, and a proportional-integral-derivative controller was used to modulate the temperature. Its operation was demonstrated in a phantom as well as in mouse and rat animal models, where the standard deviation of the temperature of the animal upon convergence was less than a 10th of a degree. An application where brain temperature of a mouse was modulated was demonstrated using an invasive optical probe and noninvasive magnetic resonance spectroscopic thermometry measurements.

¹ H-MRSI is commonly performed with gradient phase encoding, due to its simplicity and minimal radio frequency (RF) heating (specific absorption rate). Its two well-known main problems-(i) "voxel bleed" due to the intrinsic point-spread function, and (ii) chemical shift displacement error (CSDE) when slice-selective RF pulses are used, which worsens with increasing volume of interest (VOI) size-have long become accepted as unavoidable. Both problems can be mitigated with Hadamard multislice RF encoding. This is demonstrated and quantified with numerical simulations, in a multislice phantom and in five healthy young adult volunteers at 3 T, targeting a 2-cm thick temporal lobe VOI through the bilateral hippocampus. This frequently targeted region (e.g. in epilepsy and Alzheimer's disease) is subject to strong, 1-2 ppm.cm^-1 regional B0, susceptibility gradients that can dramatically reduce the signal-to-noise ratio (SNR) and water suppression effectiveness. The chemical shift imaging (CSI) sequence used a 3-ms Shinnar-Le Roux (SLR) 90° RF pulse, acquiring eight steps in the slice direction. The Hadamard sequence acquired two overlapping slices using the same SLR 90° pulses, under twofold stronger gradients that proportionally halved the CSDE. Both sequences used 2D 20 × 20 rosette spectroscopic imaging (RSI) for in-plane spatial localization and both used RF and gradient performance characteristics that are easily met by all modern MRI instruments. The results show that Hadamard spectroscopic imaging (HSI) suffered dramatically less signal bleed within the VOI compared with CSI (<1% vs. approximately 26% in simulations; and 5%-8% vs. >50%) in a phantom specifically designed to test these effects. The voxels' SNR per unit volume per unit time was also 40% higher for HSI. In a group of five healthy volunteers, we show that HSI with in-plane 2D-RSI facilitates fast, 3D multivoxel encoding at submilliliter spatial resolution, over the bilateral human hippocampus, in under 10 min, with negligible CSDE, spectral and spatial contamination and more than 6% improved SNR per unit time per unit volume.

For the spectroscopic assessment of brain disorders that require large-volume coverage, the requirements of RF performance and field homogeneity are high. For epilepsy, this is also challenging given the inter-patient variation in location, severity and subtlety of anatomical identification and its tendency to involve the temporal region. We apply a targeted method to examine the utility of large-volume MR spectroscopic imaging (MRSI) in surgical epilepsy patients, implementing a two-step acquisition, comprised of a 3D acquisition to cover the fronto-parietal regions, and a contiguous parallel two-slice Hadamard-encoded acquisition to cover the temporal-occipital region, both with T_R /T_E = 2000/40 ms and matched acquisition times. With restricted (static, first/second-order) B₀ shimming in their respective regions, the Cramér-Rao lower bounds for creatine from the temporal lobe two-slice Hadamard and frontal-parietal 3D acquisition are 8.1 ± 2.2% and 6.3 ± 1.9% respectively. The datasets are combined to provide a total 60 mm axial coverage over the frontal, parietal and superior temporal to middle temporal-occipital regions. We applied these acquisitions at a nominal 400 mm³ voxel resolution in n = 27 pre-surgical epilepsy patients and n = 20 controls. In controls, 86.6 ± 3.2% voxels with at least 50% tissue (white + gray matter, excluding CSF) survived spectral quality inclusion criteria. Since all patients were clinically followed for at least 1 year after surgery, seizure frequency outcome was available for all. The MRSI measurements of the total fractional metabolic dysfunction (characterized by the Cr/NAA metric) in FreeSurfer MRI gray matter segmented regions, in the patients compared with the controls, exhibited a significant Spearman correlation with post-surgical outcome. This finding suggests that a larger burden of metabolic dysfunction is seen in patients with poorer post-surgical seizure control.

Recent implications of glutamatergic signaling in a wide range of psychiatric disorders has highlighted the need to study the dynamics of glutamate (Glu) in the brain outside of steady state. A promising modality for doing so is functional Magnetic Resonance Spectroscopy (fMRS). Recent human studies at high magnetic fields (7T) have reported small but consistent changes in metabolite concentrations, in particular a 2-4% increase in Glu during visual and motor stimulation. While the origins of these changes remain the topic of ongoing research, the ability of fMRS to observe metabolites directly associated with neurotransmission and brain energetics could potentially aid our understanding of brain pathophysiology and the interpretation of functional imaging experiments. For this to happen, the current ultrahigh field results must be reproduced at lower, widely available clinical field strengths, in response to a wide variety of stimuli classes. Our goal herein was to investigate metabolite changes during a hand-clenching motor task at 3T, and to investigate the effect of the stimulation's temporal characteristics on the magnitude of the fMRS changes; specifically, we compared two block-designed functional activation paradigms, using short- and long-cycled clenching designs. Small but statistically significant increases in Glx=Glutamate+Glutamine (3.8%) and Glu (4.0%) concentrations were detected during the long-cycled design, while no statistically significant changes were observed during the short-cycled design. Activation during the long-cycled tasks was correlated to the frequency of clenching. We have also shown that using subject-level analysis in combination with a linear mixed model increases the observed effect size, and could help analyzing the weak MRS signals. Our results are in good agreement with the previous reports acquired at higher field systems, and support the viability of fMRS as a research tool at clinical field strengths, while also emphasizing the importance of the functional paradigm itself.

B₀ field maps are used ubiquitously in neuroimaging, in disciplines ranging from magnetic resonance spectroscopy to temperature mapping and susceptibility-weighted imaging. Most B₀ maps are acquired using standard gradient-echo-based vendor-provided sequences, often comprised of two echoes spaced a few milliseconds apart. Herein, we analyze the optimal spacing of echo times, defined as those maximizing precision-minimizing the standard deviation-for a fixed total acquisition time. Field estimation is carried out using a weighted least squares estimator. The standard deviation is shown to be approximately inversely proportional to the total acquisition time, suggesting a law of diminishing returns, whereby substantial gains are obtained up to a certain point, with little improvement beyond that point. Validations are provided in a phantom and a group of volunteers. Multi-gradient echo sequences are readily available on all manufacturer platforms, making our recommendations straightforward to implement on any modern scanner.

PURPOSE/OBJECTIVE:). To test whether knowledge of these additional parameters can improve the clinical utility of brain MRS, we compare the conventional and multiparametric approaches in terms of expected classification accuracy in differentiating controls from patients with neurological disorders. THEORY AND METHODS/UNASSIGNED:(conventional MRS); using metabolite concentrations corrected using per-subject values (multiparametric MRS); and using an optimal linear multiparametric estimator comprised of the metabolites' concentrations and relaxation constants (multiparametric MRS). Additional simulations were conducted to find the minimal intra-subject precision needed for each parameter. RESULTS:Compared with conventional MRS, multiparametric approaches yielded area under the curve improvements for almost all neuropathologies and regions of interest. The median area under the curve increased by 0.14 over the entire dataset, and by 0.24 over the 10 instances with the largest individual increases. CONCLUSIONS:Multiparametric MRS can substantially improve the clinical utility of MRS in diagnosing and assessing brain pathology, motivating the design and use of novel multiparametric sequences.

Clinical magnetic resonance spectroscopy (MRS) mainly concerns itself with the quantification of metabolite concentrations. Metabolite relaxation values, which reflect the microscopic state of specific cellular and sub-cellular environments, could potentially hold additional valuable information, but are rarely acquired within clinical scan times. By varying the flip angle, repetition time and echo time in a preset way (termed a schedule), and matching the resulting signals to a pre-generated dictionary - an approach dubbed magnetic resonance fingerprinting - it is possible to encode the spins' relaxation times into the acquired signal, simultaneously quantifying multiple tissue parameters for each metabolite. Herein, we optimized the schedule to minimize the averaged root mean square error (RMSE) across all estimated parameters: concentrations, longitudinal and transverse relaxation time, and transmitter inhomogeneity. The optimal schedules were validated in phantoms and, subsequently, in a cohort of healthy volunteers, in a 4.5 mL parietal white matter single voxel and an acquisition time under 5 minutes. The average intra-subject, inter-scan coefficients of variation (CVs) for metabolite concentrations, T₁ and T₂ relaxation times were found to be 3.4%, 4.6% and 4.7% in-vivo, respectively, averaged over all major singlets. Coupled metabolites were quantified using the short echo time schedule entries and spectral fitting, and reliable estimates of glutamate+glutamine, glutathione and myo-inositol were obtained.

BACKGROUND:H MRS with the ability to separate tissue-type partial volume contribution(s). PURPOSE/OBJECTIVE:H MRSI voxel averaging is sensitive to regional WM metabolic abnormalities. STUDY TYPE/METHODS:Retrospective cross-sectional cohort study. POPULATION/METHODS:Twenty-seven subjects: 15 symptomatic mTBI patients, 12 matched controls. FIELD STRENGTH/SEQUENCE/UNASSIGNED:. ASSESSMENT/RESULTS:N-acetyl-aspartate (NAA), creatine, choline, and myo-inositol concentrations estimated in predominantly WM regions: body, genu, and splenium of the corpus callosum, corona radiata, frontal, and occipital WM. STATISTICAL TESTS/UNASSIGNED:Analysis of covariance (ANCOVA) to compare patients with controls in terms of regional concentrations. The effect sizes (Cohen's d) of the mean differences were compared across regions and with previously published global data obtained with linear regression of the WM over the entire VOI in the same dataset. RESULTS:Despite patients' global VOI WM NAA being significantly lower than the controls', no regional differences were observed for any metabolite. Regional NAA comparisons, however, were all unidirectional (patients' NAA concentrations < controls') within a narrow range: 0.3 ≤ Cohen's d ≤ 0.6. DATA CONCLUSION/UNASSIGNED:H MRS studies, given that these results are confirmed in other cohorts. LEVEL OF EVIDENCE/METHODS:2 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2019.

PURPOSE/OBJECTIVE:To design and implement a multislice MRSI method for fast spectroscopic imaging, using a modified version of echo planar spectroscopic imaging (EPSI) that offers higher spectral width and/or shorter scan time. METHODS:Echo planar spectroscopic imaging suffers from inconsistencies between readout lines acquired with gradients of opposite signs, which has typically been addressed by reconstructing the "positive" and "negative" data sets separately and averaging the two. Nevertheless, consistency between the readout lines of each phase encode can be achieved by interposing the EPSI readouts with alternating "blipped" phase-encode gradients. This method exchanges inconsistencies along the temporal dimension with inconsistencies along the phase-encode dimension, which are straightforward to correct, as is conventionally done in various EPI reconstruction schemes. Such consistent k-t-space EPSI doubles the spectral width in comparison to EPSI, or, in an alternative realization, yields the same spectral width as EPSI, but at half the acquisition time. In this work, multiband CAIPIRINHA (controlled aliasing in parallel imaging results in higher acceleration) slice selection was integrated with consistent k-t-space EPSI to further accelerate the measurement 2-fold. RESULTS:The feasibility of a consistent k-t-space EPSI was demonstrated in both phantoms and in vivo brain imaging at 3 T, and four pulse scheme variants were evaluated. It was demonstrated to be useful in optimizing the spectral width and scan acceleration, both of which are limiting factors in vivo. Dual-band implementation was shown to shorten the duration of the scan 4-fold. CONCLUSION/CONCLUSIONS:The consistent k-t-space EPSI can be used to accelerate MRSI or, alternatively, double its spectral width. Adding dual-band CAIPIRINHA further accelerates the acquisition by a factor of 2.

PURPOSE/OBJECTIVE:measurements. METHODS:values were extracted for each model and protocol. RESULTS:recovery, whereas smaller contribution was caused by MMP interactions. Inter-slice gap had a similar effect on in vivo MTR (21.2%), in comparison to increasing the number of slices (18.9%). CONCLUSIONS:.