Vascular Aging in the Choroid Plexus: A 7T Ultrasmall Superparamagnetic Iron Oxide (USPIO)-MRI Study.

BACKGROUND: The choroid plexus (ChP), a densely vascularized structure, has drawn increasing attention for its involvement in brain homeostasis and waste clearance. While the volumetric changes have been explored in many imaging studies, few studies have investigated the vascular degeneration associated with aging in the ChP. PURPOSE: To investigate the sub-structural characteristics of the ChP, particularly the vascular compartment using high-resolution 7T imaging enhanced with Ferumoxytol, an ultrasmall super-paramagnetic iron oxide, which greatly increase the susceptibility contrast for vessels. STUDY TYPE: Prospective. SUBJECTS: Forty-nine subjects without neurological disorders (age: 21-80 years; 42 ± 17 years; 20 females). FIELD STRENGTH/SEQUENCE: 7-T with 2D and 3D T2* GRE, 3D MPRAGE T1, 2D TSE T2, and 2D FLAIR. ASSESSMENT: The vascular and stromal compartments of the ChP were segmented using K-means clustering on post-contrast 2D GRE images. Visual and qualitative assessment of ChP vascular characteristics were conducted independently by three observers. Vascular density (Volvessel/VolChP ratio) and susceptibility change (Δχ) induced by Ferumoxytol were analyzed on 3D GRE-derived susceptibility-weighted imaging and quantitative susceptibility mapping, respectively. STATISTICAL TESTS: Independent t-test, Mann-Whitney U test, and Chi-square test were utilized for group comparisons. The relationship between age and ChP's vascular alterations was examined using Pearson's correlation. Intra-class coefficient was calculated for inter-observer agreement. A P value <0.05 was considered statistically significant. RESULTS: 2D GRE images demonstrated superior contrast and accurate delineation of ChP substructures (ICC = 0.86). Older subjects exhibited a significantly smaller vascular density (16.5 ± 4.34%) and lower Δχ (22.10 ± 12.82 ppb) compared to younger subjects (24.85 ± 6.84% and 34.64 ± 12.69 ppb). Vascular density and mean Δχ within the ChP negatively correlated with age (r = -0.48, and r = -0.45). DATA CONCLUSION: Ferumoxytol-enhanced 7T images can demonstrate ChP alterations in elderly with decreased vascular density and expansion of nonvascular compartment. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 2.

In vivo mapping of hippocampal venous vasculature and oxygenation using susceptibility imaging at 7T.

Mapping the small venous vasculature of the hippocampus in vivo is crucial for understanding how functional changes of hippocampus evolve with age. Oxygen utilization in the hippocampus could serve as a sensitive biomarker for early degenerative changes, surpassing hippocampal tissue atrophy as the main source of information regarding tissue degeneration. Using an ultrahigh field (7T) susceptibility-weighted imaging (SWI) sequence, it is possible to capture oxygen-level dependent contrast of submillimeter-sized vessels. Moreover, the quantitative susceptibility mapping (QSM) results derived from SWI data allow for the simultaneous estimation of venous oxygenation levels, thereby enhancing the understanding of hippocampal function. In this study, we proposed two potential imaging markers in a cohort of 19 healthy volunteers aged between 20 and 74 years. These markers were: 1) hippocampal venous density on SWI images and 2) venous susceptibility (Δχvein) in the hippocampus-associated draining veins (the inferior ventricular veins (IVV) and the basal veins of Rosenthal (BVR) using QSM images). They were chosen specifically to help characterize the oxygen utilization of the human hippocampus and medial temporal lobe (MTL). As part of the analysis, we demonstrated the feasibility of measuring hippocampal venous density and Δχvein in the IVV and BVR at 7T with high spatial resolution (0.25 × 0.25 × 1 mm3). Our results demonstrated the in vivo reconstruction of the hippocampal venous system, providing initial evidence regarding the presence of the venous arch structure within the hippocampus. Furthermore, we evaluated the age effect of the two quantitative estimates and observed a significant increase in Δχvein for the IVV with age (p=0.006, r2 = 0.369). This may suggest the potential application of Δχvein in IVV as a marker for assessing changes in atrophy-related hippocampal oxygen utilization in normal aging and neurodegenerative diseases such as AD and dementia.

Three-dimensional multi-parameter brain mapping using MR fingerprinting.

The purpose of this study was to develop and test a 3D multi-parameter MR fingerprinting (MRF) method for brain imaging applications. The subject cohort included 5 healthy volunteers, repeatability tests done on 2 healthy volunteers and tested on two multiple sclerosis (MS) patients. A 3D-MRF imaging technique capable of quantifying T1, T2 and T1ρ was used. The imaging sequence was tested in standardized phantoms and 3D-MRF brain imaging with multiple shots (1, 2 and 4) in healthy human volunteers and MS patients. Quantitative parametric maps for T1, T2, T1ρ, were generated. Mean gray matter (GM) and white matter (WM) ROIs were compared for each mapping technique, Bland-Altman plots and intra-class correlation coefficient (ICC) were used to assess repeatability and Student T-tests were used to compare results in MS patients. Standardized phantom studies demonstrated excellent agreement with reference T1/T2/T1ρ mapping techniques. This study demonstrates that the 3D-MRF technique is able to simultaneously quantify T1, T2 and T1ρ for tissue property characterization in a clinically feasible scan time. This multi-parametric approach offers increased potential to detect and differentiate brain lesions and to better test imaging biomarker hypotheses for several neurological diseases, including MS.

Cerebral metabolic rate of oxygen (CMRO2) changes measured with simultaneous tDCS-MRI in healthy adults.

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: We investigated the simultaneous effects of tDCS on cerebral blood flow (CBF), venous blood oxygenation (Yv) and cerebral metabolic rate of oxygen (CMRO2) using simultaneous MRI in healthy adults to provide a reference frame for its neurobiological mechanisms. METHODS: Twenty-three healthy participants (age = 35.6 ± 15.0 years old, 10 males) completed a simultaneous tDCS-MRI session in a 3 T scanner fitted with a 64-channels head coil. A MR-compatible tDCS device was used to acquire CBF, Yv and CMRO2 at three time points: pre-, during- and post- 15 minutes of 2.0 mA tDCS on left anodal dorsolateral prefrontal cortex. RESULTS: During tDCS, CBF significantly increased (57.10 ± 8.33 mL/100g/min) from baseline (53.67 ± 7.75 mL/100g/min; p < 0.0001) and remained elevated in post-tDCS (56.79 ± 8.70 mL/100g/min). Venous blood oxygenation levels measured in pre-tDCS (60.71 ± 4.12 %) did not significantly change across the three timepoints. The resulting CMRO2 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: tDCS has immediate effects on neuronal excitability, as measured by increased cerebral blood supply and oxygen consumption supporting increased neuronal firing. These findings provide a standard range of CBF and CMRO2 changes due to tDCS in healthy adults that may be incorporated in clinical studies to evaluate its therapeutic potential.

Age-Related Tortuosity of Carotid and Vertebral Arteries: Quantitative Evaluation With MR Angiography.

Background and Purpose: 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: 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: Independent t-test showed that older subjects had higher tortuosity metrics, whereas lower blood flow and velocity than young subjects (p < 0.0025, Bonferroni-corrected). Cerebral blood flow calculated using the sum flux of four target arteries normalized by the brain mass also showed significantly lower values in older subjects (p < 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: 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.

Upright versus supine MRI: effects of body position on craniocervical CSF flow.

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.