Huston, John

Rationale Trials conducted decades ago demonstrated that carotid endarterectomy by skilled surgeons reduced stroke risk in asymptomatic patients. Developments in carotid stenting and improvements in medical prevention of stroke caused by atherothrombotic disease challenge understanding of the benefits of revascularization. Aim Carotid Revascularization and Medical Management for Asymptomatic Carotid Stenosis Trial (CREST-2) will test whether carotid endarterectomy or carotid stenting plus contemporary intensive medical therapy is superior to intensive medical therapy alone in the primary prevention of stroke in patients with high-grade asymptomatic carotid stenosis. Methods and design CREST-2 is two multicenter randomized trials of revascularization plus intensive medical therapy versus intensive medical therapy alone. One trial randomizes patients to carotid endarterectomy plus intensive medical therapy versus intensive medical therapy alone; the other, to carotid stenting plus intensive medical therapy versus intensive medical therapy alone. The risk factor targets of centrally directed intensive medical therapy are LDL cholesterol <70 mg/dl and systolic blood pressure <140 mmHg. Study outcomes The primary outcome is the composite of stroke and death within 44 days following randomization and stroke ipsilateral to the target vessel thereafter, up to four years. Change in cognition and differences in major and minor stroke are secondary outcomes. Sample size Enrollment of 1240 patients in each trial provides 85% power to detect a treatment difference if the event rate in the intensive medical therapy alone arm is 4.8% higher or 2.8% lower than an anticipated 3.6% rate in the revascularization arm. Discussion Management of asymptomatic carotid stenosis requires contemporary randomized trials to address whether carotid endarterectomy or carotid stenting plus intensive medical therapy is superior in preventing stroke beyond intensive medical therapy alone. Whether carotid endarterectomy or carotid stenting has favorable effects on cognition will also be tested. Trial registration United States National Institutes of Health Clinicaltrials.gov NCT02089217

PurposeTo investigate the ability of slip interface imaging (SII), a recently developed magnetic resonance elastography (MRE)‐based technique, to predict the degree of meningioma–brain adhesion, using findings at surgery as the reference standard.Materials and MethodsWith Institutional Review Board approval and written informed consent, 25 patients with meningiomas >2.5 cm in maximal diameter underwent preoperative SII assessment. Intracranial shear motions were introduced using a soft, pillow‐like head driver and the resulting displacement field was acquired with an MRE pulse sequence on 3T MR scanners. The displacement data were analyzed to determine tumor–brain adhesion by assessing intensities on shear line images and raw as well as normalized octahedral shear strain (OSS) values along the interface. The SII findings of shear line images, OSS, and normalized OSS were independently and blindly correlated with surgical findings of tumor adhesion by using the Cohen's κ coefficient and chi‐squared test.ResultsNeurosurgeons categorized the surgical plane as extrapial (no adhesion) in 15 patients, mixed in four, and subpial (adhesion) in six. Both shear line images and OSS agreed with the surgical findings in 18 (72%) cases (fair agreement, κ = 0.37, 95% confidence interval [CI]: 0.05–0.69), while normalized OSS was concordant with the surgical findings in 23 (92%) cases (good agreement, κ = 0.86, 95% CI: 0.67–1). The correlation between SII predictions (shear line images, OSS, and normalized OSS) and the surgical findings were statistically significant (chi‐squared test, P = 0.02, P = 0.02, and P < 0.0001, respectively).ConclusionSII preoperatively evaluates the degree of meningioma–brain adhesion noninvasively, allowing for improved prediction of surgical risk and tumor resectability.Level of Evidence: 1Technical Efficacy: Stage 1J. Magn. Reson. Imaging 2017;46:1007–1016.

Abstract Due to engineering limitations, the spatial encoding gradient fields in conventional magnetic resonance imaging cannot be perfectly linear and always contain higher-order, nonlinear components. If ignored during image reconstruction, gradient nonlinearity (GNL) manifests as image geometric distortion. Given an estimate of the GNL field, this distortion can be corrected to a degree proportional to the accuracy of the field estimate. The GNL of a gradient system is typically characterized using a spherical harmonic polynomial model with model coefficients obtained from electromagnetic simulation. Conventional whole-body gradient systems are symmetric in design; typically, only odd-order terms up to the 5th-order are required for GNL modeling. Recently, a high-performance, asymmetric gradient system was developed, which exhibits more complex GNL that requires higher-order terms including both odd- and even-orders for accurate modeling. This work characterizes the GNL of this system using an iterative calibration method and a fiducial phantom used in ADNI (Alzheimer’s Disease Neuroimaging Initiative). The phantom was scanned at different locations inside the 26 cm diameter-spherical-volume of this gradient, and the positions of fiducials in the phantom were estimated. An iterative calibration procedure was utilized to identify the model coefficients that minimize the mean-squared-error between the true fiducial positions and the positions estimated from images corrected using these coefficients. To examine the effect of higher-order and even-order terms, this calibration was performed using spherical harmonic polynomial of different orders up to the 10th-order including even- and odd-order terms, or odd-order only. The results showed that the model coefficients of this gradient can be successfully estimated. The residual root-mean-squared-error after correction using up to the 10th-order coefficients was reduced to 0.36 mm, yielding spatial accuracy comparable to conventional whole-body gradients. The even-order terms were necessary for accurate GNL modeling. In addition, the calibrated coefficients improved image geometric accuracy compared with the simulation-based coefficients.

Abstract Neurological disorders are one of the most important public health concerns in developed countries. Established brain imaging techniques such as magnetic resonance imaging (MRI) and x-ray computerised tomography (CT) have been essential in the identification and diagnosis of a wide range of disorders, although usually are insufficient in sensitivity for detecting subtle pathological alterations to the brain prior to the onset of clinical symptoms—at a time when prognosis for treatment is more favourable. The mechanical properties of biological tissue provide information related to the strength and integrity of the cellular microstructure. In recent years, mechanical properties of the brain have been visualised and measured non-invasively with magnetic resonance elastography (MRE), a particularly sensitive medical imaging technique that may increase the potential for early diagnosis. This review begins with an introduction to the various methods used for the acquisition and analysis of MRE data. A systematic literature search is then conducted to identify studies that have specifically utilised MRE to investigate the human brain. Through the conversion of MRE-derived measurements to shear stiffness (kPa) and, where possible, the loss tangent (rad), a summary of results for global brain tissue and grey and white matter across studies is provided for healthy participants, as potential baseline values to be used in future clinical investigations. In addition, the extent to which MRE has revealed significant alterations to the brain in patients with neurological disorders is assessed and discussed in terms of known pathophysiology. The review concludes by predicting the trends for future MRE research and applications in neuroscience.

PurposeTo investigate the effects on echo planar imaging (EPI) distortion of using high gradient slew rates (SR) of up to 700 T/m/s for in vivo human brain imaging, with a dedicated, head‐only gradient coil.Materials and MethodsSimulation studies were first performed to determine the expected echo spacing and distortion reduction in EPI. A head gradient of 42‐cm inner diameter and with asymmetric transverse coils was then installed in a whole‐body, conventional 3T magnetic resonance imaging (MRI) system. Human subject imaging was performed on five subjects to determine the effects of EPI on echo spacing and signal dropout at various gradient slew rates. The feasibility of whole‐brain imaging at 1.5 mm‐isotropic spatial resolution was demonstrated with gradient‐echo and spin‐echo diffusion‐weighted EPI.ResultsAs compared to a whole‐body gradient coil, the EPI echo spacing in the head‐only gradient coil was reduced by 48%. Simulation and in vivo results, respectively, showed up to 25–26% and 19% improvement in signal dropout. Whole‐brain imaging with EPI at 1.5 mm spatial resolution provided good whole‐brain coverage, spatial linearity, and low spatial distortion effects.ConclusionOur results of human brain imaging with EPI using the compact head gradient coil at slew rates higher than in conventional whole‐body MR systems demonstrate substantially improved image distortion, and point to a potential for benefits to non‐EPI pulse sequences. J. Magn. Reson. Imaging 2016;44:653–664.

PurposeTo investigate the feasibility of utilizing brain stiffness as a potential biomarker for behavioral variant frontotemporal dementia (bvFTD) patients. Magnetic resonance elastography (MRE) is a noninvasive technique for evaluating the mechanical properties of brain tissue in vivo. MRE has demonstrated decreased brain stiffness in patients with Alzheimer's disease.Materials and MethodsWe examined five male subjects with bvFTD and nine cognitively normal age‐matched male controls (NC) with brain 3T MRE. Stiffness was calculated in nine regions of interest (ROIs): whole brain (entire cerebrum excluding cerebellum), frontal lobes, occipital lobes, parietal lobes, temporal lobes, deep gray matter / white matter (GM/WM; insula, deep gray nuclei and white matter tracts), cerebellum, sensorimotor cortex (pre‐ and postcentral gyri), and a composite region labeled FT (frontal and temporal lobes excluding the pre‐ and postcentral gyri).ResultsSignificantly lower stiffness values were observed in the whole brain (P = 0.007), frontal lobe (P = 0.001), and temporal lobes (P = 0.005) of bvFTD patients compared to NC. No significant stiffness differences were observed in any other ROIs of bvFTD patients compared to NC (P > 0.05). These results demonstrate that statistically significant brain softening occurs in the frontal and temporal lobes of bvFTD patients, which corresponds to the expected pathophysiology of bvFTD.ConclusionFuture studies evaluating the feasibility of brain MRE for early disease detection and monitoring disease progression could shed new insights into understanding the mechanisms involved in bvFTD. J. Magn. Reson. Imaging 2016;43:474–478.

PurposeTo characterize peripheral nerve stimulation (PNS) of an asymmetric head‐only gradient coil that is compatible with a commercial high–channel‐count receive‐only array.MethodsTwo prototypes of an asymmetric head‐only gradient coil set with a 42‐cm inner diameter were constructed for brain imaging at 3T with maximum performance specifications of up to 85 mT/m and 708 T/m/s. Tests were performed in 24 volunteers to measure PNS thresholds with the transverse (x = left–right; y = anterior–posterior [A/P]) gradient coils of both prototypes. Fourteen of these 24 volunteers were also tested for the z‐gradient PNS in the second prototype and were scanned with high–slew‐rate echo planar imaging (EPI) immediately after the PNS tests.ResultsFor both prototypes, the y‐gradient PNS threshold was markedly higher than the x‐gradient threshold. The z‐gradient threshold was intermediate between those for the x‐ and y‐coils. Of the 24 volunteers, only two experienced y‐gradient PNS at 80 mT/m and 500 T/m/s. All volunteers underwent the EPI scan without PNS when the readout direction was set to A/P.ConclusionMeasured PNS characteristics of asymmetric head‐only gradient coil prototypes indicate that such coils, especially in the A/P direction, can be used for fast EPI readout in high‐performance neuroimaging scans with substantially reduced PNS concerns compared with conventional whole body gradient coils. Magn Reson Med 76:1939–1950, 2016. © 2015 International Society for Magnetic Resonance in Medicine