Retrospective correction of second-order concomitant fields in 3D axial stack-of-spirals imaging on a high-performance gradient system.

PURPOSE: MRI using 3D stack-of-spirals (SoS) readout on a high-performance gradient system is subject to strong second-order, spatially varying concomitant fields, which can lead to signal dropout and blurring artifacts that become more significant at locations farther from the gradient isocenter. A method for compensating for second-order concomitant fields in 3D axial SoS image reconstruction is described. METHODS: We retrospectively correct for second-order concomitant field-induced phase error in the 3D SoS data by slice-dependent k-space phase compensation based on the nominal spiral readout trajectories. The effectiveness of the method was demonstrated in phantom and healthy volunteer scans in which 3D pseudo-continuous arterial spin labeling imaging was performed with SoS fast spin-echo readout at 3 T. RESULTS: Substantial reduction in blurring was observed with the proposed method. In phantom scans, blurring was reduced by about 53% at 98 mm from the gradient isocenter. In the in vivo 3D pseudo-continuous arterial spin labeling scans, differences of up to 10% were observed at 78 mm from the isocenter, especially around the white-matter and gray-matter interfaces, between the corrected and uncorrected proton density images, perfusion-weighted images, and cerebral blood flow maps. CONCLUSIONS: The described retrospective correction method provides a means to correct erroneous phase accruals due to second-order concomitant fields in 3D axial stack-of-spirals imaging.

Calibration of concomitant field offsets using phase contrast MRI for asymmetric gradient coils.

PURPOSE: Asymmetric gradient coils introduce zeroth- and first-order concomitant field terms, in addition to higher-order terms common to both asymmetric and symmetric gradients. Salient to compensation strategies is the accurate calibration of the concomitant field spatial offset parameters for asymmetric coils. A method that allows for one-time calibration of the offset parameters is described. THEORY AND METHODS: A modified phase contrast pulse sequence with single-sided bipolar flow encoding is proposed to calibrate the offsets for asymmetric, transverse gradient coils. By fitting the measured phase offsets to different gradient amplitudes, the spatial offsets were calculated by fitting the phase variation. This was used for calibrating real-time pre-emphasis compensation of the zeroth- and first-order concomitant fields. RESULTS: Image quality improvement with the proposed corrections was demonstrated in phantom and healthy volunteers with non-Cartesian and Cartesian trajectory acquisitions. Concomitant field compensation using the calibrated offsets resulted in a residual phase error <3% at the highest gradient amplitude and demonstrated substantial reduction of image blur and slice position/selection artifacts. CONCLUSIONS: The proposed implementation provides an accurate method for calibrating spatial offsets that can be used for real-time concomitant field compensation of zeroth and first-order terms, substantially reducing artifacts without retrospective correction or sequence specific waveform modifications.

Metabolic assessment of a migraine model using relaxation-enhanced 1 H spectroscopy at ultrahigh field.

PURPOSE: This study evaluates biochemical imbalances in a rat model that reflects dysfunctional pathways in migraine. The high sensitivity and spectral dispersion available to 1 H MRS at 21.1 T expands metabolic profiling in this migraine model to include lactate (Lac), taurine (Tau), aspartate, and Gly-a mixture of glycine, glutamine, and glutamate. METHODS: Sprague-Dawley male rats were administered in situ an intraperitoneal injection of nitroglycerin (NTG) to induce the migraine analogue or saline as a control. A selective relaxation-enhanced MR spectroscopy sequence was used to target upfield metabolites from a 4-mm3 voxel for 2.5 h after injection. RESULTS: Significant increases were evident for Lac as early as 10 min after NTG injection, peaking over 50% compared with baseline and control (normalized Lac/N-acetyl aspartate with NTG = 1.54 ± 0.65 versus with saline = 0.99 ± 0.08). Tau decreased progressively in controls over 2 h after injection, but remained elevated with NTG, peaking at 105 min after injection (normalized Tau/N-acetyl aspartate with NTG = 1.10 ± 0.18 versus with saline = 0.85 ± 0.14). Total creatine under NTG showed significant decreases with time and compared with saline; Gly demonstrated temporal increases for NTG. CONCLUSIONS: These changes indicate an altered metabolic profile in the migraine analogue consistent with early changes in neural activity and/or vasodilation consistent with progressively enhanced neuroprotection and osmoregulation. Magn Reson Med 79:1266-1275, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Endogenous Na+, K+-ATPase inhibitors and CSF [Na+] contribute to migraine formation.

There is strong evidence that neuronal hyper-excitability underlies migraine, and may or may not be preceded by cortical spreading depression. However, the mechanisms for cortical spreading depression and/or migraine are not established. Previous studies reported that cerebrospinal fluid (CSF) [Na+] is higher during migraine, and that higher extracellular [Na+] leads to hyper-excitability. We raise the hypothesis that altered choroid plexus Na+, K+-ATPase activity can cause both migraine phenomena: inhibition raises CSF [K+] and initiates cortical spreading depression, while activation raises CSF [Na+] and causes migraine. In this study, we examined levels of specific Na+, K+-ATPase inhibitors, endogenous ouabain-like compounds (EOLC), in CSF from migraineurs and controls. CSF EOLC levels were significantly lower during ictal migraine (0.4 nM +/- 0.09) than from either controls (1.8 nM +/- 0.4) or interictal migraineurs (3.1 nM +/- 1.9). Blood plasma EOLC levels were higher in migraineurs than controls, but did not differ between ictal and interictal states. In a Sprague-Dawley rat model of nitroglycerin-triggered central sensitization, we changed the concentrations of EOLC and CSF sodium, and measured aversive mechanical threshold (von Frey hairs), trigeminal nucleus caudalis activation (cFos), and CSF [Na+] (ultra-high field 23Na MRI). Animals were sensitized by three independent treatments: intraperitoneal nitroglycerin, immunodepleting EOLC from cerebral ventricles, or cerebroventricular infusion of higher CSF [Na+]. Conversely, nitroglycerin-triggered sensitization was prevented by either vascular or cerebroventricular delivery of the specific Na+, K+-ATPase inhibitor, ouabain. These results affirm our hypothesis that higher CSF [Na+] is linked to human migraine and to a rodent migraine model, and demonstrate that EOLC regulates them both. Our data suggest that altered choroid plexus Na+, K+-ATPase activity is a common source of these changes, and may be the initiating mechanism in migraine.

Dynamic sodium imaging at ultra-high field reveals progression in a preclinical migraine model.

Under the hypothesis that increased extracellular sodium induces sustained neuronal excitability with the onset and progression of migraine, this study evaluates dynamic in vivo Na fluxes in the brain of a preclinical rodent analogue of migraine. Ultra-high field Na magnetic resonance imaging (MRI) at 21.1 T has demonstrated potential to quantify sodium concentrations with good spatial and temporal resolution after the onset of central sensitization. Sprague-Dawley male rats with implanted intraperitoneal lines were studied by MRI before and after an in situ injection of 10 mg/kg of nitroglycerin (NTG) vs vehicle and saline controls. Slice-selective Na images were acquired using a multislice free induction decay-based chemical shift imaging sequence with resolution of 1.1 × 1.1 × 3 mm for a 9-minute acquisition. A total of 27 repeated scans were acquired over 1 hour of baseline scanning and longitudinally up to 3 hours after injection. Increases of Na MRI signal in the brainstem, extracerebral cerebrospinal fluid, and cisterna magna were evident almost immediately after NTG injection, gaining significance from controls in 36 minutes. The cerebellum and third ventricle also showed sustained trends of increased Na, with the former gaining significance at over 2 hours after NTG injection. The data provide evidence of an early change in sodium concentration, markedly in posterior fossa cerebrospinal fluid and brainstem regions. Further study of fluctuations of sodium concentration and their modulation with treatments could help understand the dynamic features of migraine, locate a putative migraine generator, and guide development of therapeutic measures to correct the disturbance of sodium homeostasis.

Use of human mesenchymal stem cell treatment to prevent anhedonia in a rat model of traumatic brain injury.

PURPOSE: Major depression and related mood disorders are the most common long-term outcomes associated with traumatic brain injury (TBI). Given the potentially debilitating consequences of depression, and the fact that TBI patients are frequently refractory to antidepressant drugs, new therapies are clearly needed. We hypothesized that human bone marrow-derived mesenchymal stem cells (hMSC), delivered intravenously, can effectively treat TBI-induced depression and other behavioral deficits associated with TBI. METHODS: Rats (n = 8 per group) were subjected to experimental TBI or control sham operation. Six hours post TBI, rats were treated with 1×106 hMSC or vehicle control. Immediately after TBI and prior to hMSC or control treatment, rats were subjected to either targeted precision x-ray irradiation to eliminate subventricular zone (SVZ) proliferation or sham irradiation. One week after TBI, SVZ irradiation, and hMSC treatment, rats were evaluated for the depression-like behavior, anhedonia, using the two-bottle saccharin preference paradigm; and for working memory using the novel object recognition test. RESULTS: TBI resulted in a 54% (p≤0.05) decrease in saccharin preference scores while treatment of TBI with hMSC fully prevented this anhedonic behavior. TBI was also found to produce a 73% (p≤0.05) decrease in novel object interaction time, indicating impaired working memory, and was similarly improved by treatment with hMSC. The ability of hMSC to prevent TBI-associated depression and working memory impairment was eliminated when SVZ proliferation was inhibited by irradiation. CONCLUSIONS: This work has identified a possible role for hMSC in the treatment of TBI-induced depression and other behaviors and suggests a mechanistic role for proliferative cells of the SVZ proliferation in hMSC efficacy.