Lindsey M. Dethrage

Routine Clinical Evaluation of Cerebrovascular Reserve Capacity Using Carbogen in Patients With Intracranial Stenosis

Background and Purpose— A promising method for identifying hemodynamic impairment that may serve as a biomarker for stroke risk in patients with intracranial stenosis is cerebrovascular reactivity (CVR) mapping using noninvasive MRI. Here, abilities to measure CVR safely in the clinic using hypercarbic hyperoxic (carbogen) gas challenges, which increase oxygen delivery to tissue, are investigated. Methods— In sequence with structural and angiographic imaging, blood oxygenation level–dependent carbogen-induced CVR scans were performed in patients with symptomatic intracranial stenosis (n=92) and control (n=10) volunteers, with a subgroup of patients (n=57) undergoing cerebral blood flow–weighted pseudocontinuous arterial spin labeling CVR. Subjects were stratified for 4 substudies to evaluate relationships between (1) carbogen and hypercarbic normoxic CVR in healthy tissue (n=10), (2) carbogen cerebral blood flow CVR and blood oxygenation level–dependent CVR in intracranial stenosis patients (n=57), (3) carbogen CVR and clinical measures of disease in patients with asymmetrical intracranial atherosclerotic (n=31) and moyamoya (n=29) disease, and (4) the CVR scan and immediate and longer-term complications (n=92). Results— Noninvasive blood oxygenation level–dependent carbogen-induced CVR values correlate with (1) lobar hypercarbic normoxic gas stimuli in healthy tissue (R=0.92; P<0.001), (2) carbogen-induced cerebral blood flow CVR in patients with intracranial stenosis (R=0.30–0.33; P<0.012), and (3) angiographic measures of disease severity both in atherosclerotic and moyamoya patients after appropriate processing. No immediate stroke-related complications were reported in response to carbogen administration; longer-term neurological events fell within the range for expected events in this patient population. Conclusions— Carbogen-induced CVR elicited no added adverse events and provided a surrogate marker of cerebrovascular reserve consistent with intracranial vasculopathy.

Bolus arrival time and cerebral blood flow responses to hypercarbia

The purpose of this study was to evaluate how cerebral blood flow and bolus arrival time (BAT) measures derived from arterial spin labeling (ASL) MRI data change for different hypercarbic gas stimuli. Pseudocontinuous ASL (pCASL) was applied (3.0T; spatial resolution = 4 × 4 × 7 mm 3 ; repetition time/echo time (TR/TE) = 3,600/11 ms) sequentially in healthy volunteers (n = 12; age = 30±4 years) for separate experiments in which (i) normocarbic normoxia (i.e., room air), hypercarbic normoxia (i.e., 5% CO2/21% O2/74% N2), and hypercarbic hyperoxia (i.e., carbogen: 5% CO2/95% O2) gas was administered (12 L/minute). Cerebral blood flow and BAT changes were quantified using models that account for macrovascular signal and partial volume effects in all gray matter and regionally in cerebellar, temporal, occipital, frontal, and parietal lobes. Regional reductions in BAT of 4.6% to 7.7% and 3.3% to 6.6% were found in response to hypercarbic normoxia and hypercarbic hyperoxia, respectively. Cerebral blood flow increased by 8.2% to 27.8% and 3.5% to 19.8% for hypercarbic normoxia and hypercarbic hyperoxia, respectively. These findings indicate that changes in BAT values may bias functional ASL data and thus should be considered when choosing appropriate experimental parameters in calibrated functional magnetic resonance imaging or ASL cerebrovascular reactivity experiments that use hypercarbic gas stimuli.

Magnetic resonance imaging of the cervical spinal cord in multiple sclerosis at 7T.

Background: The clinical course of multiple sclerosis (MS) is mainly attributable to cervical and upper thoracic spinal cord dysfunction. High-resolution, 7T anatomical imaging of the cervical spinal cord is presented. Image contrast between gray/white matter and lesions surpasses conventional, clinical T1- and T2-weighted sequences at lower field strengths. Objective: To study the spinal cord of healthy controls and patients with MS using magnetic resonance imaging at 7T. Methods: Axial (C2–C5) T1- and T2*-weighted and sagittal T2*-/spin-density-weighted images were acquired at 7T in 13 healthy volunteers (age 22–40 years), and 15 clinically diagnosed MS patients (age 19–53 years, Extended Disability Status Scale, (EDSS) 0–3) in addition to clinical 3T scans. In healthy volunteers, a high-resolution multi-echo gradient echo scan was obtained over the same geometry at 3T. Evaluation included signal and contrast to noise ratios and lesion counts for healthy and patient volunteers, respectively. Results/conclusion: High-resolution images at 7T exceeded resolutions reported at lower field strengths. Gray and white matter were sharply demarcated and MS lesions were more readily visualized at 7T compared to clinical acquisitions, with lesions apparent at both fields. Nerve roots were clearly visualized. White matter lesion counts averaged 4.7 vs 3.1 (52% increase) per patient at 7T vs 3T, respectively (p=0.05).

Rapid, high-resolution quantitative magnetization transfer MRI of the human spinal cord.

Quantitative magnetization transfer (qMT) imaging can provide indices describing the interactions between free water protons and immobile macromolecular protons. These indices include the macromolecular proton fraction (MPF), which has been shown to correlate with myelin content in white matter. Because of the long scan times required for high-resolution spinal cord imaging, qMT studies of the human spinal cord have not found wide-spread application. Herein, we investigated whether these limitations could be overcome by utilizing only a single MT-weighted acquisition and a reference measurement, as was recently proposed in the brain. High-resolution, in vivo qMT data were obtained at 3.0T in the spinal cords of healthy volunteers and patients with relapsing remitting multiple sclerosis (MS). Low- and high-resolution acquisitions (low/high resolution=1×1×5mm(3)/0.65×0.65×5mm(3)) with clinically acceptable scan times (12min/7min) were evaluated. We also evaluated the reliability over time and the sensitivity of the model to the assumptions made in the single-point method, both in disease and healthy tissues. Our findings suggest that the single point qMT technique can provide maps of the MPF in the spinal cord in vivo with excellent grey/white matter contrast, can be reliably obtained within reasonable scan times, and are sensitive to MS pathology. Consistent with previous qMT studies in the brain, the observed MPF values were higher in healthy white matter (0.16±0.01) than in grey matter (0.13±0.01) and in MS lesions (0.09±0.01). The single point qMT technique applied at high resolution provides an improved method for obtaining qMT in the human spinal cord and may offer a reliable outcome measure for evaluating spinal cord disease.

Dual echo vessel-encoded ASL for simultaneous BOLD and CBF reactivity assessment in patients with ischemic cerebrovascular disease

Blood oxygenation level‐dependent (BOLD)‐weighted and vessel‐encoded arterial spin labeling (VE‐ASL) MRI provide complementary information and can be used in sequence to gauge hemodynamic contributions to cerebrovascular reactivity. Here, cerebrovascular reactivity is assessed using dual echo VE‐ASL MRI to understand how VE labeling preparations influence BOLD and ASL contrast in flow‐limited and healthy perfusion territories.

Proximal nerve magnetization transfer MRI relates to disability in Charcot-Marie-Tooth diseases.

Objective: The objectives of this study were (1) to develop a novel magnetization transfer ratio (MTR) MRI assay of the proximal sciatic nerve (SN), which is inaccessible via current tools for assessing peripheral nerves, and (2) to evaluate the resulting MTR values as a potential biomarker of myelin content changes in patients with Charcot-Marie-Tooth (CMT) diseases. Methods: MTR was measured in the SN of patients with CMT type 1A (CMT1A, n = 10), CMT type 2A (CMT2A, n = 3), hereditary neuropathy with liability to pressure palsies (n = 3), and healthy controls (n = 21). Additional patients without a genetically confirmed subtype (n = 4), but whose family histories and electrophysiologic tests were consistent with CMT, were also included. The relationship between MTR and clinical neuropathy scores was assessed, and the interscan and inter-rater reliability of MTR was estimated. Results: Mean volumetric MTR values were significantly decreased in the SN of patients with CMT1A (33.8 ± 3.3 percent units) and CMT2A (31.5 ± 1.9 percent units) relative to controls (37.2 ± 2.3 percent units). A significant relationship between MTR and disability scores was also detected (p = 0.01 for genetically confirmed patients only, p = 0.04 for all patients). From interscan and inter-rater reliability analyses, proximal nerve MTR values were repeatable at the slicewise and mean volumetric levels. Conclusions: MTR measurements may be a viable biomarker of proximal nerve pathology in patients with CMT.

The vascular steal phenomenon is an incomplete contributor to negative cerebrovascular reactivity in patients with symptomatic intracranial stenosis.

‘Vascular steal’ has been proposed as a compensatory mechanism in hemodynamically compromised ischemic parenchyma. Here, independent measures of cerebral blood flow (CBF) and blood oxygenation level-dependent (BOLD) magnetic resonance imaging (MRI) responses to a vascular stimulus in patients with ischemic cerebrovascular disease are recorded. Symptomatic intracranial stenosis patients (n = 40) underwent a multimodal 3.0T MRI protocol including structural (T1-weighted and T2-weighted fluid-attenuated inversion recovery) and hemodynamic (BOLD and CBF-weighted arterial spin labeling) functional MRI during room air and hypercarbic gas administration. CBF changes in regions demonstrating negative BOLD reactivity were recorded, as well as clinical correlates including symptomatic hemisphere by infarct and lateralizing symptoms. Fifteen out of forty participants exhibited negative BOLD reactivity. Of these, a positive relationship was found between BOLD and CBF reactivity in unaffected (stenosis degree <50%) cortex. In negative BOLD cerebrovascular reactivity regions, three patients exhibited significant (P < 0.01) reductions in CBF consistent with vascular steal; six exhibited increases in CBF; and the remaining exhibited no statistical change in CBF. Secondary findings were that negative BOLD reactivity correlated with symptomatic hemisphere by lateralizing clinical symptoms and prior infarcts(s). These data support the conclusion that negative hypercarbia-induced BOLD responses, frequently assigned to vascular steal, are heterogeneous in origin with possible contributions from autoregulation and/or metabolism.

Chemical exchange saturation transfer of the cervical spinal cord at 7 T

High‐magnetic‐field (7 T) chemical exchange saturation transfer (CEST) MRI provides information on the tissue biochemical environment. Multiple sclerosis (MS) affects the entire central nervous system, including the spinal cord. Optimal CEST saturation parameters found via simulation were implemented for CEST MRI in 10 healthy controls and 10 patients with MS, and the results were examined using traditional asymmetry analysis and a Lorentzian fitting method. In addition, T1‐ and T2*‐weighted images were acquired for lesion localization and the transmitted B1+ field was evaluated to guide imaging parameters. Distinct spectral features for all tissue types studied were found both up‐ and downfield from the water resonance. The z spectra in healthy subjects had the expected z spectral shape with CEST effects apparent from 2.0 to 4.5 ppm. The z spectra from patients with MS demonstrated deviations from this expected normal shape, indicating this methods sensitivity to known pathology as well as to tissues appearing normal on conventional MRI. Examination of the calculated CESTasym revealed increased asymmetry around the amide proton resonance (Δω = 3.5 ppm), but it was apparent that this measure is complicated by detail in the CEST spectrum upfield from water, which is expected to result from the nuclear Overhauser effect. The z spectra upfield (negative ppm range) were also distinct between healthy and diseased tissue, and could not be ignored, particularly when considering the conventional asymmetry analysis used to quantify the CEST effect. For all frequencies greater than +1 ppm, the Lorentzian differences (and z spectra) for lesions and normal‐appearing white matter were distinct from those for healthy white matter. The increased frequency separation and signal‐to‐noise ratio, in concert with prolonged T1 at 7 T, resulted in signal enhancements necessary to detect subtle tissue changes not possible at lower field strengths. This study presents CEST imaging metrics that may be sensitive to the extensive and temporally varying biochemical neuropathology of MS in the spinal cord. Copyright

The Contribution of Common Surgically Implanted Hardware to Functional MR Imaging Artifacts

The authors calculated the BOLD-dependent MR imaging artifact impact arising from surgically implanted hardware through a retrospective analysis of fMRIs acquired from 2006–2014. Mean artifact volume associated with intracranial hardware was 4.3 cubic centimeters. The mean artifact volume from extracranial hardware in patients with cerebrovascular disease was 28.4 cubic centimeters. Artifacts had no-to-mild effects on clinical interpretability in all patients with intracranial implants. Extracranial hardware artifacts had no-to-moderate impact on clinical interpretability. The exceptions to interpretability in the face of hardware were ventriculoperitoneal shunts, particularly those with programmable valves and siphon gauges, and large numbers of KLS-Martin maxDrive screws. BACKGROUND AND PURPOSE: Blood oxygenation level–dependent MR imaging is increasingly used clinically to noninvasively assess cerebrovascular reactivity and/or language and motor function. However, many patients have metallic implants, which will induce susceptibility artifacts, rendering the functional information uninformative. Here, we calculate and interpret blood oxygenation level–dependent MR imaging artifact impact arising from surgically implanted hardware. MATERIALS AND METHODS: A retrospective analysis of all blood oxygenation level–dependent MRIs (n = 343; B0 = 3T; TE = 35 ms; gradient echo EPI) acquired clinically (year range = 2006–2014) at our hospital was performed. Blood oxygenation level–dependent MRIs were most commonly prescribed for patients with cerebrovascular disease (n = 80) or patients undergoing language or motor localization (n = 263). Artifact volume (cubic centimeters) and its impact on clinical interpretation were determined by a board-certified neuroradiologist. RESULTS: Mean artifact volume associated with intracranial hardware was 4.3 ± 3.2 cm3 (range = 1.1–9.4 cm3). The mean artifact volume from extracranial hardware in patients with cerebrovascular disease was 28.4 ± 14.0 cm3 (range = 6.1–61.7 cm3), and in patients with noncerebrovascular disease undergoing visual or motor functional mapping, it was 39.9 3± 27.0 cm3 (range = 6.9–77.1 cm3). The mean artifact volume for ventriculoperitoneal shunts was 95.7 ± 39.3 cm3 (range = 64.0–139.6 cm3). Artifacts had no-to-mild effects on clinical interpretability in all patients with intracranial implants. Extracranial hardware artifacts had no-to-moderate impact on clinical interpretability, with the exception of 1 patient with 12 KLS-Martin maxDrive screws with severe artifacts precluding clinical interpretation. All examined ventriculoperitoneal shunts resulted in moderate-to-severe artifacts, limiting clinical interpretation. CONCLUSIONS: Blood oxygenation level–dependent MR imaging yields interpretable functional maps in most patients beyond a small (30–40 cm3) artifact surrounding the hardware. Exceptions were ventriculoperitoneal shunts, particularly those with programmable valves and siphon gauges, and large numbers of KLS-Martin maxDrive screws.

Quantifying the impact of underlying measurement error on cervical spinal cord diffusion tensor imaging at 3T

To empirically characterize and quantify the impact of gradient weighting schemes on the appearance and fidelity of diffusion tensor imaging of the human spinal cord in vivo in clinically relevant scan time equivalents (STE).