Sexual Dimorphism of Radiomic Features in the Brain: An Exploratory Study Using 700 µm MP2RAGE MRI at 7 T.

OBJECTIVES: The aim of this study was to determine whether MRI radiomic features of key cerebral structures differ between women and men, and whether detection of such differences depends on the image resolution. MATERIALS AND METHODS: Ultrahigh resolution (UHR) 3D MP2RAGE (magnetization-prepared 2 rapid acquisition gradient echo) T1-weighted MR images (voxel size, 0.7 × 0.7 × 0.7 mm3) of the brain of 30 subjects (18 women and 12 men; mean age, 39.0 ± 14.8 years) without abnormal findings on MRI were retrospectively included. MRI was performed on a whole-body 7 T MR system. A convolutional neural network was used to segment the following structures: frontal cortex, frontal white matter, thalamus, putamen, globus pallidus, caudate nucleus, and corpus callosum. Eighty-seven radiomic features were extracted respectively: gray-level histogram (n = 18), co-occurrence matrix (n = 24), run-length matrix (n = 16), size-zone matrix (n = 16), and dependence matrix (n = 13). Feature extraction was performed at UHR and, additionally, also after resampling to 1.4 × 1.4 × 1.4 mm3 voxel size (standard clinical resolution). Principal components (PCs) of radiomic features were calculated, and independent samples t tests with Cohen d as effect size measure were used to assess differences in PCs between women and men for the different cerebral structures. RESULTS: At UHR, at least a single PC differed significantly between women and men in 6/7 cerebral structures: frontal cortex (d = -0.79, P = 0.042 and d = -1.01, P = 0.010), frontal white matter (d = -0.81, P = 0.039), thalamus (d = 1.43, P < 0.001), globus pallidus (d = 0.92, P = 0.020), caudate nucleus (d = -0.83, P = 0.039), and corpus callosum (d = -0.97, P = 0.039). At standard clinical resolution, only a single PC extracted from the corpus callosum differed between sexes (d = 1.05, P = 0.009). CONCLUSIONS: Nonnegligible differences in radiomic features of several key structures of the brain exist between women and men, and need to be accounted for. Very high spatial resolution may be required to uncover and further investigate the sexual dimorphism of brain structures on MRI.

Map-based B0 shimming for single voxel brain spectroscopy at 7T.

While B0 shimming is an important requirement for in vivo brain spectroscopy, for single voxel spectroscopy (SVS), the role for advanced shim methods has been questioned. Specifically, with the small spatial dimensions of the voxel, the extent to which inhomogeneities higher than second order exist and the ability of higher order shims to correct them is controversial. To assess this, we acquired SVS from two loci of neurophysiological interest, the rostral prefrontal cortex (rPFC; 8 cc) and hippocampus (Hc; 9 cc). The rPFC voxel was placed using SUsceptibility Managed Optimization (SUMO) and an initial B0 map that covers the entire cerebrum to cerebellum. In each location, we compared map-based shimming (Bolero) with projection-based shimming (FAST(EST)MAP). We also compared vendor-provided spherical harmonic first- and second-order shims with additional third- and fourth-order shim hardware. The 7T SVS acquisition used stimulated echo acquisition mode (STEAM) TR/TM/TE of 6 s/20 ms/8 ms, a tissue water acquisition for concentration reference, and LCModel for spectral analysis. In the rPFC (n = 7 subjects), Bolero shimming with first- and second-order shims reduced the residual inhomogeneity σ B 0 from 9.8 ± 4.5 Hz with FAST(EST)MAP to 6.5 ± 2.0 Hz. The addition of third- and fourth-order shims further reduced σ B 0 to 4.0 ± 0.8 Hz. In the Hc (n = 7 subjects), FAST(EST)MAP, Bolero with first- and second-order shims, and Bolero with first- to fourth-order shims achieved σ B 0 values of 8.6 ± 1.9, 5.6 ± 1.0, and 4.6 ± 0.9 Hz, respectively. The spectral linewidth, Δ v σ B 0 , was estimated with a Voigt lineshape using σ B 0 and T2 = 130 ms. Δ v σ B 0 significantly correlated with the Cramer-Rao lower bounds and concentrations of several metabolites, including glutamate and glutamine in the rPFC. In both loci, if the B0 distribution is well described by a Gaussian model, the variance of the metabolite concentrations is reduced, consistent with the LCModel fit based on a unimodal lineshape. Overall, the use of the high order and map-based B0 shim methods improved the accuracy and consistency of spectroscopic data.

Intracranial monitoring contributes to seizure freedom for temporal lobectomy patients with nonconcordant preoperative data.

OBJECTIVE: The question of whether a patient with presumed temporal lobe seizures should proceed directly to temporal lobectomy surgery versus undergo intracranial monitoring arises commonly. We evaluate the effect of intracranial monitoring on seizure outcome in a retrospective cohort of consecutive subjects who specifically underwent an anterior temporal lobectomy (ATL) for refractory temporal lobe epilepsy (TLE). METHODS: We performed a retrospective analysis of 85 patients with focal refractory TLE who underwent ATL following: (a) intracranial monitoring via craniotomy and subdural/depth electrodes (SDE/DE), (b) intracranial monitoring via stereotactic electroencephalography (sEEG), or (c) no intracranial monitoring (direct ATL-dATL). For each subject, the presurgical primary hypothesis for epileptogenic zone localization was characterized as unilateral TLE, unilateral TLE plus (TLE+), or TLE with bilateral/poor lateralization. RESULTS: At one-year and most recent follow-up, Engel Class I and combined I/II outcomes did not differ significantly between the groups. Outcomes were better in the dATL group compared to the intracranial monitoring groups for lesional cases but were similar in nonlesional cases. Those requiring intracranial monitoring for a hypothesis of TLE+had similar outcomes with either intracranial monitoring approach. sEEG was the only approach used in patients with bilateral or poorly lateralized TLE, resulting in 77.8% of patients seizure-free at last follow-up. Importantly, for 85% of patients undergoing SEEG, recommendation for ATL resulted from modifying the primary hypothesis based on iEEG data. SIGNIFICANCE: Our study highlights the value of intracranial monitoring in equalizing seizure outcomes in difficult-to-treat TLE patients undergoing ATL.

MR spectroscopic imaging at 3 T and outcomes in surgical epilepsy.

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 TR /TE = 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.

Fast, regional three-dimensional hybrid (1D-Hadamard 2D-rosette) proton MR spectroscopic imaging in the human temporal lobes.

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.

Electromagnetic simulation of a 16-channel head transceiver at 7 T using circuit-spatial optimization.

PURPOSE: With increased interest in parallel transmission in ultrahigh-field MRI, methods are needed to correctly calculate the S-parameters and complex field maps of the parallel transmission coil. We present S-parameters paired with spatial field optimization to fully simulate a double-row 16-element transceiver array for brain MRI at 7 T. METHODS: We implemented a closed-form equation of the coil S-parameters and overall spatial B1+ field. We minimized a cost function, consisting of coil S-parameters and the B1+ homogeneity in brain tissue, by optimizing transceiver components, including matching, decoupling circuits, and lumped capacitors. With this, we are able to compare the in silico results determined with and without B1+ homogeneity weighting. Using the known voltage range from the host console, we reconstructed the B1+ maps of the array and performed RF shimming with four realistic head models. RESULTS: As performed with B1+ homogeneity weighting, the optimized coil circuit components were highly consistent over the four heads, producing well-tuned, matched, and decoupled coils. The mean peak forward powers and B1+ statistics for the head models are consistent with in vivo human results (N = 8). There are systematic differences in the transceiver components as optimized with or without B1+ homogeneity weighting, resulting in an improvement of 28.4 ± 7.5% in B1+ homogeneity with a small 1.9 ± 1.5% decline in power efficiency. CONCLUSION: This co-simulation methodology accurately simulates the transceiver, predicting consistent S-parameters, component values, and B1+ field. The RF shimming of the calculated field maps match the in vivo performance.

7T Epilepsy Task Force Consensus Recommendations on the Use of 7T MRI in Clinical Practice.

Identifying a structural brain lesion on MRI has important implications in epilepsy and is the most important factor that correlates with seizure freedom after surgery in patients with drug-resistant focal onset epilepsy. However, at conventional magnetic field strengths (1.5 and 3T), only approximately 60%-85% of MRI examinations reveal such lesions. Over the last decade, studies have demonstrated the added value of 7T MRI in patients with and without known epileptogenic lesions from 1.5 and/or 3T. However, translation of 7T MRI to clinical practice is still challenging, particularly in centers new to 7T, and there is a need for practical recommendations on targeted use of 7T MRI in the clinical management of patients with epilepsy. The 7T Epilepsy Task Force-an international group representing 21 7T MRI centers with experience from scanning over 2,000 patients with epilepsy-would hereby like to share its experience with the neurology community regarding the appropriate clinical indications, patient selection and preparation, acquisition protocols and setup, technical challenges, and radiologic guidelines for 7T MRI in patients with epilepsy. This article mainly addresses structural imaging; in addition, it presents multiple nonstructural MRI techniques that benefit from 7T and hold promise as future directions in epilepsy. Answering to the increased availability of 7T MRI as an approved tool for diagnostic purposes, this article aims to provide guidance on clinical 7T MRI epilepsy management by giving recommendations on referral, suitable 7T MRI protocols, and image interpretation.

Dynamic B0 shimming for multiband imaging using high order spherical harmonic shims.

PURPOSE: To describe and implement a strategy for dynamic slice-by-slice and multiband B0 shimming using spherical harmonic shims in the human brain at 7T. THEORY: For thin axial slices, spherical harmonic shims can be divided into pairs of shims (z-degenerate and non-z-degenerate) that are spatially degenerate, such that only ½ of the shims (non-z-degenerate) are required for single slice optimizations. However, when combined, the pairs of shims can be used to simultaneously generate the same in-plane symmetries but with different amplitudes as a function of their z location. This enables multiband shimming equivalent to that achievable by single slice-by-slice optimization. METHODS: All data were acquired at 7T using a spherical harmonic shim insert enabling shimming up through 4th order with two additional 5th order shims (1st-4th+). Dynamic shim updating was achieved using a 10A shim power supply with 2 ms ramps and constrained optimizations to minimize eddy currents. RESULTS: In groups of eight subjects, we demonstrated that: 1) dynamic updating using 1st-4th+ order shims reduced the SD of the B0 field over the whole brain from 32.4 ± 2.6 and 24.9 ± 2 Hz with 1st-2nd and 1st-4th+ static global shimming to 15.1 ± 1.7 Hz; 2) near equivalent performance was achieved when dynamically updating only the non-z-degenerate shims (14.3 ± 1.5 Hz), or when a using multiband shim factor of 2, MBs = 2, and all shims (14.4 ± 2.0 Hz). CONCLUSION: High order spherical harmonics provide substantial improvements over static global shimming and enable dynamic multiband shimming with near equivalent performance to that of dynamic slice-by-slice shimming. This reduces distortion in echo planar imaging.

Modelling and B1 Shim Analysis of 16-Element Transceiver Array at 7 T.

The work examines the workflow of using commercially available software for electromagnetic modelling and validation of a transceiver array coil operating at 298 MHz for magnetic resonance imaging and spectroscopy at 7 T. The coneshaped, tight-fit parallel transmit head array consists of two rows with eight loop coils per row and transmits two distinct spatial distributions by means of B 1 shimming. Considerations for finite-difference time-domain simulation setup and post-processing with circuit-domain co-simulation are examined, as is the generation of virtual observation points suitable for online safety monitoring.

Cerebrospinal fluid-suppressed T2 -weighted MR imaging at 7 T for human brain.

PURPOSE: T2 -weighted lesional imaging is most commonly performed using inversion recovery turbo spin echoes. At 7 T, however, this acquisition is limited for specific absorption rate and resolution. This work describes and implements a method to generate CSF-suppressed T2 -weighted imaging. METHODS: The strategy uses a driven equilibrium spin-echo preparation within an inversion recovery with multiple 3D gradient-echo imaging blocks. Images are combined using the self-normalization approach, which achieves CSF suppression through optimized timing of individual blocks and minimizes sources of variation due to coil receptivity, T2* , and proton density. Simulations of the magnetization-prepared fluid-attenuated inversion recovery gradient-echo (MPFLAGRE) method over T1 and T2 relaxation values are performed, and in vivo demonstrations using an 8 × 2 transceiver array in healthy controls are shown. RESULTS: The specific absorption rate of the calculated MPFLAGRE sequence is 11.1 ± 0.5 W (n = 5 volunteers), which is 74 ± 2% of the US Food and Drug Administration guidelines. This method acquires both contrasts for CSF suppression with detection of long T2 components and T2 -weighted imaging in a single acquisition. In healthy controls, the former contrast generates increased signal in the cortical rim and ependyma. A comparison is shown with a conventional 3D SPACE fluid-attenuated inversion recovery acquisition, and sensitivity to pathology is demonstrated in an epilepsy patient. CONCLUSION: As applied with the 8 × 2 transceiver, the MPFLAGRE sequence generates both whole-brain contrast suitable for lesional and T2 -weighted imaging at 7 T in fewer than 10 minutes within the US Food and Drug Administration's specific absorption rate guidelines.

Fast 3D rosette spectroscopic imaging of neocortical abnormalities at 3 T: Assessment of spectral quality.

PURPOSE: To use a fast 3D rosette spectroscopic imaging acquisition to quantitatively evaluate how spectral quality influences detection of the endogenous variation of gray and white matter metabolite differences in controls, and demonstrate how rosette spectroscopic imaging can detect metabolic dysfunction in patients with neocortical abnormalities. METHODS: Data were acquired on a 3T MR scanner and 32-channel head coil, with rosette spectroscopic imaging covering a 4-cm slab of fronto-parietal-temporal lobes. The influence of acquisition parameters and filtering on spectral quality and sensitivity to tissue composition was assessed by LCModel analysis, the Cramer-Rao lower bound, and the standard errors from regression analyses. The optimized protocol was used to generate normative white and gray matter regressions and evaluate three patients with neocortical abnormalities. RESULTS: As a measure of the sensitivity to detect abnormalities, the standard errors of regression for Cr/NAA and Ch/NAA were significantly correlated with the Cramer-Rao lower bound values (R = 0.89 and 0.92, respectively, both with P < 0.001). The rosette acquisition with a duration of 9.6 min, produces a mean Cramer-Rao lower bound (%) over the entire slab of 4.6 ± 2.6 and 5.8 ± 2.3 for NAA and Cr, respectively. This enables a Cr/NAA standard error of 0.08 (i.e., detection sensitivity of 25% for a 50/50 mixed gray and white matter voxel). In healthy controls, the regression of Cr/NAA versus fraction gray matter in the cingulate differs from frontal and parietal regions. CONCLUSIONS: Fast rosette spectroscopic imaging acquisitions with regression analyses are able to identify metabolic differences across 4-cm slabs of the brain centrally and over the cortical periphery with high efficiency, generating results that are consistent with clinical findings. Magn Reson Med 79:2470-2480, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Whole brain neuronal abnormalities in focal epilepsy quantified with proton MR spectroscopy.

OBJECTIVE: To test the hypothesis that localization-related epilepsy is associated with widespread neuronal dysfunction beyond the ictal focus, reflected by a decrease in patients' global concentration of their proton MR spectroscopy (1H-MRS) observed marker, N-acetyl-aspartate (NAA). METHODS: Thirteen patients with localization-related epilepsy (7 men, 6 women) 40±13 (mean±standard-deviation)years old, 8.3±13.4years of disease duration; and 14 matched controls, were scanned at 3 T with MRI and whole-brain (WB) 1H MRS. Intracranial fractions of brain volume, gray and white matter (fBV, fGM, fWM) were segmented from the MRI, and global absolute NAA creatine (Cr) and choline (Cho) concentrations were estimated from their WB 1H MRS. These metrics were compared between patients and controls using an unequal variance t test. RESULTS: Patients' fBV, fGM and fWM: 0.81±0.07, 0.47±0.04, 0.31±0.04 were not different from controls' 0.79±0.05, 0.48±0.04, 0.32±0.02; nor were their Cr and Cho concentrations: 7.1±1.1 and 1.3±0.2 millimolar (mM) versus 7.7±0.7 and 1.4±0.1mM (p>0.05 all). Patients' global NAA concentration: 11.5±1.5 mM, however, was 12% lower than controls' 13.0±0.8mM (p=0.004). CONCLUSIONS: These findings indicate that neuronal dysfunction in localization-related epilepsy extends globally, beyond the ictal zone, but without atrophy or spectroscopic evidence of other pathology. This suggests a diffuse decline in the neurons' health, rather than their number, early in the disease course. WB 1H-MRS assessment, therefore, may be a useful tool for quantification of global neuronal dysfunction load in epilepsy.

Clinical and Magnetic Resonance Spectroscopic Imaging Findings in Veterans With Blast Mild Traumatic Brain Injury and Post-Traumatic Stress Disorder.

OBJECTIVES: To compare magnetic resonance spectroscopic imaging (MRSI) findings from the hippocampal regions of military veterans with blast-related mild traumatic brain injury (blast mTBI) and post-traumatic stress disorder (PTSD) to those with PTSD only; and to examine the relationship of MRSI findings to cognitive and neuromotor impairment. METHODS: 35 military veterans-23 with blast mTBI and PTSD (blast mTBI/PTSD) and 12 with PTSD only participated in the study. Whole plane MRSI data including N-acetyl aspartate (NAA) and choline (Ch) were acquired at 7T for the hippocampus. Concurrent cognitive and neuromotor data were collected using established assessments. General linear models (GLMs) with Bonferroni correction were used to compare the two groups on NAA/Ch ratios across regions of the hippocampus. Spearman's correlations were used to examine correlations between NAA/Ch and cognitive and neuromotor impairment. RESULTS: The NAA/Ch results for the left hippocampus were lower in the blast mTBI/PTSD group than the PTSD-only group. The blast mTBI/PTSD group also scored worse on the WAIS-IV-vocabulary. Significant correlations between NAA/Ch and neuromotor outcomes-including vestibular impairment-were supported. CONCLUSIONS: Combined MRSI and cognitive and neuromotor data may help inform more objective and accurate diagnoses and effective treatments for patients with blast mTBI and PTSD.

Gradient-echo EPI using a high-degree shim insert coil at 7 T: Implications for BOLD fMRI.

PURPOSE: To quantitatively assess the effects of high degree and order (1st -4th+ ) relative to 1st -2nd degree B0 shimming at 7 Tesla (T) on gradient-echo echo planar imaging (GE-EPI) and blood-oxygen-level dependent (BOLD) activation. METHODS: Simulations and GE-EPI were performed at (2mm)3 and (3mm)3 resolution, evaluating the temporal signal-to-noise ratio (tSNR), transverse relaxivity ( R2*), BOLD % signal change and activated pixel counts in a breath-hold task. RESULTS: Comparing the 1st -4th+ degree with 1st -2nd degree shimmed B0 maps generated spatially varying regions of Δ|B0|=|B01-2|-|B01-4+|. As binned in 10-Hz intervals, the two center Δ|B0 | (±10 Hz) bins maintained the B0 offset of 48.6% of gray-matter pixels. In the positive Δ|B0 | bins greater than 10 Hz, the 1st -4th+ degree shimming improved the B0 offset in 41.1%; in negative Δ|B0 | bins less than -10 Hz, the offset worsened in 10.2% of the pixels. In the positive Δ|B0 | bins, we found variable but significant increases in BOLD sensitivity; the negative Δ|B0 | bins showed significant decreases. In the breath-hold studies, positive bins showed significantly increased activated pixel numbers (+5-29%), whereas negative bins showed -18 to 0% decline. CONCLUSION: 1st -4th+ degree shimming maintained B0 homogeneity over central brain regions while improving most of the other regions, including the inferior frontal lobe. Magn Reson Med 78:1734-1745, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

Metabolic injury in a variable rat model of post-status epilepticus.

OBJECTIVE: In vivo studies of epilepsy typically use prolonged status epilepticus to generate recurrent seizures. However, reports on variable status duration have found discrete differences in injury after 40-50 min of seizures, suggesting a pathophysiologic sensitivity to seizure duration. In this report we take a multivariate cluster analysis to study a short duration status epilepticus model using in vivo 7T magnetic resonance spectroscopy (MRS) and histologic evaluation. METHODS: The Hellier Dudek model was applied with 45 min of status epilepticus after which the animals were imaged twice, at 3 days and 3 weeks post-status epilepticus. Single voxel point resolved spectroscopy (PRESS) MRS was used to acquire data from the dentate gyrus and CA3 region of the hippocampus, assessing metabolite ratios to total creatine (tCr). In a subset of animals after the second imaging study, brains were analyzed histologically by Nissl staining. RESULTS: A hierarchical cluster analysis performed on the 3-day data from 21 kainate-treated animals (dentate gyrus voxel) segregated into two clusters, denoted by KM (more injured, n = 6) and KL (less injured, n = 15). Although there was no difference in kainate dosing or seizure count between them, the metabolic pattern of injury was different. The KM group displayed the largest significant changes in neuronal and glial parameters; the KL group displayed milder but significant changes. At 3 weeks, the KL group returned to normal compared to controls, whereas the KM group persisted with depressed N-acetyl aspartate (NAA)/tCr, glutamate/tCr, and increased inositol/tCr and glutamine/tCr. The classification was also consistent with subsequent histologic patterns at 3 weeks. SIGNIFICANCE: Although a short status period might be expected to generate a continuous distribution of metabolic injury, these data show that the short Hellier Dudek model appears to generate two levels of injury. The changes seen in segregated groups persisted into 3 weeks, and can be interpreted according to neuronal and glial biomarkers consistent with histology results.

Emerging roles of Na⁺/H⁺ exchangers in epilepsy and developmental brain disorders.

Epilepsy is a common central nervous system (CNS) disease characterized by recurrent transient neurological events occurring due to abnormally excessive or synchronous neuronal activity in the brain. The CNS is affected by systemic acid-base disorders, and epileptic seizures are sensitive indicators of underlying imbalances in cellular pH regulation. Na(+)/H(+) exchangers (NHEs) are a family of membrane transporter proteins actively involved in regulating intracellular and organellar pH by extruding H(+) in exchange for Na(+) influx. Altering NHE function significantly influences neuronal excitability and plays a role in epilepsy. This review gives an overview of pH regulatory mechanisms in the brain with a special focus on the NHE family and the relationship between epilepsy and dysfunction of NHE isoforms. We first discuss how cells translocate acids and bases across the membrane and establish pH homeostasis as a result of the concerted effort of enzymes and ion transporters. We focus on the specific roles of the NHE family by detailing how the loss of NHE1 in two NHE mutant mice results in enhanced neuronal excitability in these animals. Furthermore, we highlight new findings on the link between mutations of NHE6 and NHE9 and developmental brain disorders including epilepsy, autism, and attention deficit hyperactivity disorder (ADHD). These studies demonstrate the importance of NHE proteins in maintaining H(+) homeostasis and their intricate roles in the regulation of neuronal function. A better understanding of the mechanisms underlying NHE1, 6, and 9 dysfunctions in epilepsy formation may advance the development of new epilepsy treatment strategies.

In vivo brain rosette spectroscopic imaging (RSI) with LASER excitation, constant gradient strength readout, and automated LCModel quantification for all voxels.

PURPOSE: To optimize the Rosette trajectories for high-sensitivity in vivo brain spectroscopic imaging and reduced gradient demands. METHODS: Using LASER localization, a rosette based sampling scheme for in vivo brain spectroscopic imaging data on a 3 Tesla (T) system is described. The two-dimensional (2D) and 3D rosette spectroscopic imaging (RSI) data were acquired using 20 × 20 in-plane resolution (8 × 8 mm(2) ), and 1 (2D) -18 mm (1.1 cc) or 12 (3D) -8 mm partitions (0.5 cc voxels). The performance of the RSI acquisition was compared with a conventional spectroscopic imaging (SI) sequence using LASER localization and 2D or 3D elliptical phase encoding (ePE). Quantification of the entire RSI data set was performed using an LCModel based pipeline. RESULTS: The RSI acquisitions took 32 s for the 2D scan, and as short as 5 min for the 3D 20 × 20 × 12 scan, using a maximum gradient strength Gmax=5.8 mT/m and slew-rate Smax=45 mT/m/ms. The Bland-Altman agreement between RSI and ePE CSI, characterized by the 95% confidence interval for their difference (RSI-ePE), is within 13% of the mean (RSI+ePE)/2. Compared with the 3D ePE at the same nominal resolution, the effective RSI voxel size was three times smaller while the measured signal-to-noise ratio sensitivity, after normalization for differences in effective size, was 43% greater. CONCLUSION: 3D LASER-RSI is a fast, high-sensitivity spectroscopic imaging sequence, which can acquire medium-to-high resolution SI data in clinically acceptable scan times (5-10 min), with reduced stress on the gradient system. Magn Reson Med 76:380-390, 2016. © 2015 Wiley Periodicals, Inc.

Metabolic changes in early poststatus epilepticus measured by MR spectroscopy in rats.

There is little experimental in vivo data on how differences in seizure duration in experimental status epilepticus influence metabolic injury. This is of interest given that in humans, status duration is a factor that influences the probability of subsequent development of epilepsy. This question is studied using 7-T magnetic resonance (MR) spectroscopy, T2 relaxometry in the incremented kainate rodent model of temporal lobe epilepsy, using two durations of status epilepticus, 1.5 and 3 hours. Histologic evaluation was performed in a subset of animals. Three days after status, single-voxel (8 mm(3)) point resolved spectroscopy (PRESS) MR spectroscopic measurements were acquired at 7 T to assess the cerebral metabolites measured as a ratio to total creatine (tCr). The status injury resulted in decreased N-acetylaspartate NAA/tCr, increased myo-inositol/tCr and glutamine/tCr, increased T2, and significant declines in NeuN-stained neuronal counts in both status groups. Regressions were identified in the status groups that provide evidence for neuronal injury and astrocytic reaction after status in both the short and long status duration groups. The long status group displays changes in glutathione/tCr that are not identified in the short status group, this difference possibly representing a maturation of injury and antioxidant response that occurs in synchrony with glutamatergic injury and glial activation.

Utility of magnetic resonance spectroscopic imaging for human epilepsy.

This review discusses the potential utility of broad based use of magnetic resonance (MR) spectroscopic imaging for human epilepsy and seizure localization. The clinical challenges are well known to the epilepsy community, intrinsic in the variability of location, volumetric size and network extent of epileptogenic tissue in individual patients. The technical challenges are also evident, with high performance requirements in multiple steps, including magnet homogeneity, detector performance, sequence design, speed of acquisition in addition to large territory spectral processing. We consider how MR spectroscopy and spectroscopic imaging has been informative for epilepsy thus far, with specific attention to what is measured, the interpretation of such measurements and technical performance challenges. Examples are shown from medial temporal lobe and neocortical epilepsies are considered from 4T, 7T and most recently 3T.