Faculty Bibliography

Background and Purpose: Susceptibility-weighted imaging (SWI) has emerged as a useful clinical tool in many neurological diseases including multiple sclerosis (MS). This study aims to investigate the relationship between SWI signal changes due to iron deposition in MS lesions and tissue blood perfusion and microstructural abnormalities to better understand their underlying histopathologies. Methods: Forty-six patients with relapsing remitting MS were recruited for this study. Conventional FLAIR, pre- and post-contrast T1-weighted imaging, SWI, diffusion tensor imaging (DTI), and dynamic susceptibility contrast (DSC) perfusion MRI were performed in these patients at 3T. The SWI was processed using both magnitude and phase information with one slice minimal intensity projection (mIP) and phase multiplication factor of 4. MS lesions were classified into 3 types based on their lesional signal appearance on SWI mIP relative to perilesional normal appearing white matter (peri-NAWM): Type-1: hypointense, Type-2: isointense, and Type-3: hyperintense lesions. The DTI and DSC MRI data were processed offline to generate DTI-derived mean diffusivity (MD) and fractional anisotropy (FA) maps, as well as DSC-derived cerebral blood flow (CBF) and cerebral blood volume (CBV) maps. Comparisons of diffusion and perfusion measurements between lesions and peri-NAWM, as well between different types of lesions, were performed. Results: A total of 137 lesions were identified on FLAIR in these patients that include 40 Type-1, 46 Type-2, and 51 Type-3 lesions according to their SWI intensity relative to peri-NAWM. All lesion types showed significant higher MD and lower FA compared to their peri-NAWM (P < 0.0001). Compared to Type-1 lesions (likely represent iron deposition), Type-2 lesions had significantly higher MD and lower FA (P < 0.001) as well as lower perfusion measurements (P < 0.05), while Type 3 lesions had significantly higher perfusion (P < 0.001) and lower FA (P < 0.05). Compared to Type-2, Type-3 lesions had higher perfusion (P < 0.0001) and marginally higher MD and lower FA (P < 0.05). Conclusion: The significant differences in diffusion and perfusion MRI metrics associated with MS lesions, that appear with different signal appearance on SWI, may help to identify the underlying destructive pathways of myelin and axons and their evolution related to inflammatory activities.

PURPOSE/OBJECTIVE:To investigate the feasibility of measuring the subtle disruption of blood-brain barrier (BBB) using DCE-MRI with a scan duration shorter than 10 min. METHODS:) in the estimation of vascular permeability-surface area product (PS). Numerical simulation studies were carried out to investigate how the reduction in scan time affects the accuracy in estimating contrast kinetic parameters. DCE-MRI studies of the rat brain were conducted with Fisher rats to confirm the results from the simulation. Intracranial F98 glioblastoma models were used to assess areas with different levels of permeability. In the normal brain tissues, the Patlak model (PM) and EPM were compared, whereas the 2-compartment-exchange-model (TCM) and EPM were assessed in the peri-tumor and the tumor regions. RESULTS:was high as in the gray matter, the bias in PM-PS (>900%) were larger than that in EPM-PS (<42%). The animal study also showed similar results, where the PM parameters were more sensitive to the scan duration than the EPM parameters. It was also demonstrated that, in the peri-tumor region, the EPM parameters showed less change by scan duration than the TCM parameters. CONCLUSION/CONCLUSIONS:The results of this study suggest that EPM can be used to measure PS with a scan duration of 10 min or less.

PURPOSE/OBJECTIVE:Many brain diseases are associated with an alteration in blood-brain barrier (BBB) and its permeability. Current methods using contrast agent are primarily sensitive to major leakage of BBB to macromolecules, but may not detect subtle changes in BBB permeability. The present study aims to develop a novel non-contrast MRI technique for the assessment of BBB permeability to water. METHODS:The central principle is that by measuring arterially labeled blood spins that are drained into cerebral veins, water extraction fraction (E) and permeability-surface-area product (PS) of BBB can be determined. Four studies were performed. We first demonstrated the proof-of-principle using conventional ASL with very long post-labeling delays (PLD). Next, a new sequence, dubbed water-extraction-with-phase-contrast-arterial-spin-tagging (WEPCAST), and its Look-Locker (LL) version were developed. Finally, we demonstrated that the sensitivity of the technique can be significantly enhanced by acquiring the data under mild hypercapnia. RESULTS:By combining a strong background suppression with long PLDs (2500-4500 ms), ASL spins were reliably detected in the superior sagittal sinus (SSS), demonstrating the feasibility of measuring this signal. The WEPCAST sequence eliminated partial voluming effects of tissue perfusion and allowed quantitative estimation of E = 95.5 ± 1.1% and PS = 188.9 ± 13.4 mL/100 g/min, which were in good agreement with literature reports. LL-WEPCAST sequence shortened the scan time from 19 min to 5 min while providing results consistent with multiple single-PLD acquisitions. Mild hypercapnia increased SNR by 78 ± 25% without causing a discomfort in participants. CONCLUSION/CONCLUSIONS:A new non-contrast technique for the assessment of global BBB permeability was developed, which may have important clinical applications.

PURPOSE: To demonstrate the potential of imaging cerebral arteries and veins with ferumoxytol using susceptibility weighted imaging (SWI) and quantitative susceptibility mapping (QSM). MATERIALS AND METHODS: The relationships between ferumoxytol concentration and the apparent susceptibility at 1.5T, 3T, and 7T were determined using phantom data; the ability of visualizing subvoxel vessels was evaluated using simulations; and the feasibility of using ferumoxytol to enhance the visibility of small vessels was confirmed in three healthy volunteers at 7T(with doses 1 mg/kg to 4 mg/kg). The visualization of the lenticulostriate arteries and the medullary veins was assessed by two raters and the contrast-to-noise ratios (CNRs) of these vessels were measured. RESULTS: The relationship between ferumoxytol concentration and susceptibility was linear with a slope 13.3 +/- 0.2 ppm.mg-1 .mL at 7T. Simulations showed that SWI data with an increased dose of ferumoxytol, higher echo time (TE), and higher imaging resolution improved the detection of smaller vessels. With 4 mg/kg ferumoxytol, voxel aspect ratio = 1:8, TE = 10 ms, the diameter of the smallest detectable artery was approximately 50mum. The rating score for arteries was improved from 1.5 +/- 0.5 (precontrast) to 3.0 +/- 0.0 (post-4 mg/kg) in the in vivo data and the apparent susceptibilities of the arteries (0.65 +/- 0.02 ppm at 4 mg/kg) agreed well with the expected susceptibility (0.71 +/- 0.05 ppm). CONCLUSION: The CNR for cerebral vessels with ferumoxytol can be enhanced using SWI, and the apparent susceptibilities of the arteries can be reliably quantified using QSM. This approach improves the imaging of the entire vascular system outside the capillaries and may be valuable for a variety of neurodegenerative diseases which involve the microvasculature. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2017.

Pathophysiology of multiple sclerosis (MS) lesions is dynamic and changes over time. The purpose of this exploratory study was to determine the longitudinal changes in MS lesions over time on ultra-high field MR imaging. Nine patients with MS underwent high-resolution 3D-susceptibility weighted imaging (SWI) and 2D-gradient-echo-T2*-weighted imaging on 7T MRI at baseline and after ~2.4 years of follow-up. Morphologic imaging characteristics, signal intensity patterns and quantitative susceptibility mapping (QSM) values of lesions were recorded at both time points. Lesions were classified as "iron-laden" if they demonstrated hypointense signal on T2*-weighted images and/or SWI as well as hyperintense signal on QSM. Lesions were considered "non-iron-laden" if they were hyperintense on T2*/SWI and isointense or hyperintense on QSM. Total of 162 non-iron-laden and 29 iron-laden lesions were observed at baseline. No change in baseline lesion size during follow up was recorded in 92.7%; no change in lesion-vessel relationship in 86.5%; and no change in signal intensity pattern in 96.9% of lesions. Three lesions which were non-iron-laden at baseline, exhibited iron at follow-up. In two iron-laden lesions, redistribution of iron content was observed at follow-up. Two-thirds of these iron-laden lesions showed an increase in QSM at follow-up relative to baseline, and the remaining one-third exhibited decrease in QSM. Most of the newly formed lesions (11/13, 84.6%) at follow-up were iron-laden. 7T multiparametric MRI is a useful tool for tracking the evolution of MS lesions, especially with regard to changes in iron content.

The relationship between neuronal inflammatory changes and extensive neurodegeneration in patients with multiple sclerosis (MS) remains to be studied. Recent neuroimaging studies have shown that energy depletion due to the impairment of effective oxygen metabolism and oxygen supply defects may be one of the causes of neurodegeneration. In this paper, the pathologic mechanism of MS related to energy failure and associated MRI imaging techniques were reviewed.

A better understanding of the effect of oxygen on brain electrophysiological activity may provide a more mechanistic insight into clinical studies that use oxygen treatment in pathological conditions, as well as in studies that use oxygen to calibrate functional magnetic resonance imaging (fMRI) signals. This study applied electroencephalography (EEG) in healthy subjects and investigated how high a concentration of oxygen in inhaled air (i.e., normobaric hyperoxia) alters brain activity under resting-state and task-evoked conditions. Study 1 investigated its impact on resting EEG and revealed that hyperoxia suppressed alpha (8-13Hz) and beta (14-35Hz) band power (by 15.6+/-2.3% and 14.1+/-3.1%, respectively), but did not change the delta (1-3Hz), theta (4-7Hz), and gamma (36-75Hz) bands. Sham control experiments did not result in such changes. Study 2 reproduced these findings, and, furthermore, examined the effect of hyperoxia on visual stimulation event-related potentials (ERP). It was found that the main peaks of visual ERP, specifically N1 and P2, were both delayed during hyperoxia compared to normoxia (P = 0.04 and 0.02, respectively). In contrast, the amplitude of the peaks did not show a change. Our results suggest that hyperoxia has a pronounced effect on brain neural activity, for both resting-state and task-evoked potentials.

Cerebrovascular reactivity measures vascular regulation of cerebral blood flow and is responsible for maintaining healthy neurovascular coupling. Multiple sclerosis exhibits progressive neurodegeneration and global cerebrovascular reactivity deficits. This study investigates varied degrees of cerebrovascular reactivity impairment in different brain networks, which may be an underlying cause for functional changes in the brain, affecting long-distance projection integrity and cognitive function; 28 multiple sclerosis and 28 control subjects underwent pseudocontinuous arterial spin labeling perfusion MRI to measure cerebral blood flow under normocapnia (room air) and hypercapnia (5% carbon dioxide gas mixture) breathing. Cerebrovascular reactivity, measured as normocapnic to hypercapnic cerebral blood flow percent increase normalized by end-tidal carbon dioxide change, was determined from seven functional networks (default mode, frontoparietal, somatomotor, visual, limbic, dorsal, and ventral attention networks). Group analysis showed significantly decreased cerebrovascular reactivity in patients compared to controls within the default mode, frontoparietal, somatomotor, and ventral attention networks after multiple comparison correction. Regression analysis showed a significant correlation of cerebrovascular reactivity with lesion load in the default mode and ventral attention networks and with gray matter atrophy in the default mode network. Functional networks in multiple sclerosis patients exhibit varied amounts of cerebrovascular reactivity deficits. Such blood flow regulation abnormalities may contribute to functional communication disruption in multiple sclerosis.