Faculty Bibliography

BACKGROUND:Transcranial direct current stimulation (tDCS) is a safe and well-tolerated noninvasive technique used for cortical excitability modulation. tDCS has been extensively investigated for its clinical applications; however further understanding of its underlying in-vivo physiological mechanisms remains a fundamental focus of current research. OBJECTIVES/OBJECTIVE:) using simultaneous MRI in healthy adults to provide a reference frame for its neurobiological mechanisms. METHODS:at three time points: pre-, during- and post- 15 minutes of 2.0 mA tDCS on left anodal dorsolateral prefrontal cortex. RESULTS:significantly increased by 5.9 % during-tDCS (175.68 ± 30.78 µmol/100g/min) compared to pre-tDCS (165.84 ± 25.32 µmol/100g/min; p = 0.0015), maintaining increased levels in post-tDCS (176.86 ± 28.58 µmol/100g/min). CONCLUSIONS:changes due to tDCS in healthy adults that may be incorporated in clinical studies to evaluate its therapeutic potential.

INTRODUCTION/BACKGROUND:Neurological complications among hospitalized COVID-19 patients may be associated with elevated neurodegenerative biomarkers. METHODS:Among hospitalized COVID-19 patients without a history of dementia (N = 251), we compared serum total tau (t-tau), phosphorylated tau-181 (p-tau181), glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), ubiquitin carboxy-terminal hydrolase L1 (UCHL1), and amyloid beta (Aβ40,42) between patients with or without encephalopathy, in-hospital death versus survival, and discharge home versus other dispositions. COVID-19 patient biomarker levels were also compared to non-COVID cognitively normal, mild cognitive impairment (MCI), and Alzheimer's disease (AD) dementia controls (N = 161). RESULTS:Admission t-tau, p-tau181, GFAP, and NfL were significantly elevated in patients with encephalopathy and in those who died in-hospital, while t-tau, GFAP, and NfL were significantly lower in those discharged home. These markers correlated with severity of COVID illness. NfL, GFAP, and UCHL1 were higher in COVID patients than in non-COVID controls with MCI or AD. DISCUSSION/CONCLUSIONS:Neurodegenerative biomarkers were elevated to levels observed in AD dementia and associated with encephalopathy and worse outcomes among hospitalized COVID-19 patients.

The hippocampus is a small but complex grey matter structure that plays an important role in spatial and episodic memory and can be affected by a wide range of pathologies including vascular abnormalities. In this work, we introduce the use of Ferumoxytol, an ultra-small superparamagnetic iron oxide (USPIO) agent, to induce susceptibility in the arteries (as well as increase the susceptibility in the veins) to map the hippocampal micro-vasculature and to evaluate the quantitative change in tissue fractional vascular density (FVD), in each of its subfields. A total of 39 healthy subjects (aged 35.4 ± 14.2 years, from 18 to 81 years old) were scanned with a high-resolution (0.22×0.44×1 mm³) dual-echo SWI sequence acquired at four time points during a gradual increase in Ferumoxytol dose (final dose = 4 mg/kg). The volumes of each subfield were obtained automatically from the pre-contrast T₁-weighted data. The dynamically acquired SWI data were co-registered and adaptively combined to reduce the blooming artifacts from large vessels, preserving the contrast from smaller vessels. The resultant SWI data were used to segment the hippocampal vasculature and to measure the FVD ((volume occupied by vessels)/(total volume)) for each subfield. The hippocampal fissure, along with the fimbria, granular cell layer of the dentate gyrus and cornu ammonis layers (except for CA1), showed higher micro-vascular FVD than the other parts of hippocampus. The CA1 region exhibited a significant correlation with age (R = -0.37, p < 0.05). demonstrating an overall loss of hippocampal vascularity in the normal aging process. Moreover, the vascular density reduction was more prominent than the age correlation with the volume reduction (R = -0.1, p > 0.05) of the CA1 subfield, which would suggest that vascular degeneration may precede tissue atrophy.

Background and Purpose/UNASSIGNED:The vascular tortuosity (VT) of the internal carotid artery (ICA), and vertebral artery (VA) can impact blood flow and neuronal function. However, few studies involved quantitative investigation of VT based on magnetic resonance imaging (MRI). The main purpose of our study was to evaluate the age and gender effects on ICA and VA regarding the tortuosity and flow changes by applying automatic vessel segmentation, centerline tracking, and phase mapping on MR angiography. Methods/UNASSIGNED:A total of 247 subjects (86 males and 161 females) without neurological diseases participated in this study. All subjects obtained T1-weighted MRI, 3D time-of-flight MR angiography, and 2D phase-contrast (PC) MRI scans. To generate quantitative tortuosity metrics from TOF images, the vessel segmentation and centerline tracking were implemented based on Otsu thresholding and fast marching algorithms, respectively. Blood flow and velocity were measured using PC MRI. Among the 247 subjects, 144 subjects (≤ 60 years, 49 males/95 females) were categorized as the young group; 103 subjects (>60 years, 37 males/66 females) were categorized as the old group. Results/UNASSIGNED:< 0.001). The age was observed to be positively correlated with the VT metrics. Compared to the males, the females demonstrated higher geometric indices within VAs as well as faster age-related vascular profile changes. After adjusting age and gender as covariates, maximum blood velocity is negatively correlated with geometric measurements. No association was observed between blood flux and geometric measures. Conclusions/UNASSIGNED:Vascular auto-segmentation, centerline tracking, and phase mapping provide promising quantitative assessments of tortuosity and its effects on blood flow. The neck arteries demonstrate quantifiable and significant age-related morphological and hemodynamic alterations. Moreover, females showed more distinct vascular changes with age. Our work is built upon a comprehensive quantitative investigation of a large cohort of populations covering adult lifespan using MRI, the results can serve as reference ranges of each decade in the general population.

High-resolution susceptibility weighted imaging (SWI) provides unique contrast to small venous vasculature. The conspicuity of these mesoscopic veins, such as deep medullary veins in white matter, is subject to change from SWI venography when venous oxygenation in these veins is altered due to oxygenated blood susceptibility changes. The changes of visualization in small veins shows potential to depict regional changes of oxygen utilization and/or vascular density changes in the aging brain. The goal of this study was to use WM venous density to quantify small vein visibility in WM and investigate its relationship with neurodegenerative features, white matter hyperintensities (WMHs), and cognitive/functional status in elderly subjects (N = 137). WM venous density was significantly associated with neurodegeneration characterized by brain atrophy (β = 0.046± 0.01, p < 0.001), but no significant association was found between WM venous density and WMHs lesion load (p = 0.3963). Further analysis of clinical features revealed a negative trend of WM venous density with the sum-of-boxes of Clinical Dementia Rating and a significant association with category fluency (1-min animal naming). These results suggest that WM venous density on SWI can be used as a sensitive marker to characterize cerebral oxygen metabolism and different stages of cognitive and functional status in neurodegenerative diseases.

BACKGROUND:Cerebrospinal fluid (CSF) circulation between the brain and spinal canal, as part of the glymphatic system, provides homeostatic support to brain functions and waste clearance. Recently, it has been observed that CSF flow is strongly driven by cardiovascular brain pulsation, and affected by body orientation. The advancement of MRI has allowed for non-invasive examination of the CSF hydrodynamic properties. However, very few studies have addressed their relationship with body position (e.g., upright versus supine). It is important to understand how CSF hydrodynamics are altered by body position change in a single cardiac phase and how cumulative long hours staying in either upright or supine position can affect craniocervical CSF flow. METHODS:In this study, we investigate the changes in CSF flow at the craniocervical region with flow-sensitive MRI when subjects are moved from upright to supine position. 30 healthy volunteers were imaged in upright and supine positions using an upright MRI. The cranio-caudal and caudo-cranial CSF flow, velocity and stroke volume were measured at the C2 spinal level over one cardiac cycle using phase contrast MRI. Statistical analysis was performed to identify differences in CSF flow properties between the two positions. RESULTS:CSF stroke volume per cardiac cycle, representing CSF volume oscillating in and out of the cranium, was ~ 57.6% greater in supine (p < 0.0001), due to a ~ 83.8% increase in caudo-cranial CSF peak velocity during diastole (p < 0.0001) and extended systolic phase duration when moving from upright (0.25 ± 0.05 s) to supine (0.34 ± 0.08 s; p < 0.0001). Extrapolation to a 24 h timeframe showed significantly larger total CSF volume exchanged at C2 with 10 h spent supine versus only 5 h (p < 0.0001). CONCLUSIONS:In summary, body position has significant effects on CSF flow in and out of the cranium, with more CSF oscillating in supine compared to upright position. Such difference was driven by an increased caudo-cranial diastolic CSF velocity and an increased systolic phase duration when moving from upright to supine position. Extrapolation to a 24 h timeframe suggests that more time spent in supine position increases total amount of CSF exchange, which may play a beneficial role in waste clearance in the brain.

RATIONALE AND OBJECTIVES/OBJECTIVE:Periventricular and deep white matter hyperintensities (WMHs) in the elderly have been reported with distinctive roles in the progression of cognitive decline and dementia. However, the definition of these two subregions of WMHs is arbitrary and varies across studies. Here, we evaluate three partition methods for WMH subregions, including two widely used conventional methods (CV & D10) and one novel method based on bilateral distance (BD). MATERIALS AND METHODS/METHODS:The three partition methods were assessed on the MRI scans of 60 subjects, with 20 normal control, 20 mild cognitive impairment, and 20 Alzheimer's disease (AD). Resulting WMH subregional volumes were (1) compared among different partition methods and subject groups, and (2) tested for clinical associations with cognition and dementia. Inter-rater, intrarater, and interscan reproducibility of WMHs volumes were tested on 12 randomly selected subjects from the 60. RESULTS:For all three partition methods, increased periventricular WMHs were found for AD subjects over normal control. For BD and D10, but not CV method, increased Periventricular WMHs were found for AD subjects over mild cognitive impairment. Significant correlations were found between PVWMHs and Mini-Mental State Examination, Montreal Cognitive Assessment, and Clinical Dementia Rating scores. Furthermore, PVWMHs under BD partition showed higher correlations than D10 and CV. High intrarater and interscan reproducibility (ICCA = 0.998 and 0.992 correspondingly) and substantial inter-rater reproducibility (ICCA = 0.886) were detected. CONCLUSION/CONCLUSIONS:Different WMH partition methods showed comparable diagnostic abilities. The proposed BD method showed advantages in quantifying PVWMH over conventional CV and D10 methods, in terms of higher consistency, larger contrast, and higher diagnosis accuracy. Furthermore, the PVWMH under BD partition showed stronger clinical correlations than conventional methods.

PURPOSE/OBJECTIVE:To develop a deep learning-based reconstruction framework for ultrafast and robust diffusion tensor imaging and fiber tractography. METHODS:SuperDTI was developed to learn the nonlinear relationship between DWIs and the corresponding diffusion tensor parameter maps. It bypasses the tensor fitting procedure, which is highly susceptible to noises and motions in DWIs. The network was trained and tested using data sets from the Human Connectome Project and patients with ischemic stroke. Results from SuperDTI were compared against widely used methods for tensor parameter estimation and fiber tracking. RESULTS:Using training and testing data acquired using the same protocol and scanner, SuperDTI was shown to generate fractional anisotropy and mean diffusivity maps, as well as fiber tractography, from as few as six raw DWIs, with a quantification error of less than 5% in all white-matter and gray-matter regions of interest. It was robust to noises and motions in the testing data. Furthermore, the network trained using healthy volunteer data showed no apparent reduction in lesion detectability when directly applied to stroke patient data. CONCLUSIONS:Our results demonstrate the feasibility of superfast DTI and fiber tractography using deep learning with as few as six DWIs directly, bypassing tensor fitting. Such a significant reduction in scan time may allow the inclusion of DTI into the clinical routine for many potential applications.

PURPOSE/OBJECTIVE:Assessment of the blood-brain barrier (BBB) permeability without the need for contrast agent is desirable, and the ability to measure the permeability to small molecules such as water may further increase the sensitivity in detecting diseases. This study proposed a time-efficient, noncontrast method to measure BBB permeability to water, evaluated its test-retest reproducibility, and compared it with a contrast agent-based method. METHODS:A single-delay water extraction with phase-contrast arterial spin tagging (WEPCAST) method was devised in which spatial profile of the signal along the superior sagittal sinus was used to estimate bolus arrival time, and the WEPCAST signal at the corresponding location was used to compute water extraction fraction, which was combined with global cerebral blood flow to estimate BBB permeability surface area product to water. The reliability of WEPCAST sequence was examined in terms of intrasession, intersession, and inter-vendor (Philips [Ingenia, Best, the Netherlands] and Siemens [Prisma, Erlangen, Germany]) reproducibility. Finally, we compared this new technique to a contrast agent-based method. RESULTS:Single-delay WEPCAST reduced the scan duration from approximately 20 min to 5 min. Extract fraction values estimated from single-delay WEPCAST showed good consistency with the multi-delay method (R = 0.82, P = .004). Group-averaged permeability surface area product values were found to be 137.5 ± 9.3 mL/100 g/min. Intrasession, intersession, and inter-vendor coefficient of variation of the permeability surface area product values were 6.6 ± 4.5%, 6.9 ± 3.7%, and 8.9 ± 3.0%, respectively. Finally, permeability surface area product obtained from WEPCAST MRI showed a significant correlation with that from the contrast-based method (R = .73, P = .02). CONCLUSION/CONCLUSIONS:Single-delay WEPCAST MRI can measure BBB permeability to water within 5 min with an intrasession, intersession, and inter-vendor test-retest reproducibility of 6% to 9%. This method may provide a useful marker of BBB breakdown in clinical studies.