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The intricate neurofluid dynamics and balance is essential in preserving the structural and functional integrity of the brain. Key among these forces are: hemodynamics, such as heartbeat-driven arterial and venous blood flow, and hydrodynamics, such as cerebrospinal fluid (CSF) circulation. The delicate interplay between these dynamics is crucial for maintaining optimal homeostasis within the brain. Currently, the widely accepted framework for understanding brain functions is the Monro-Kellie’s doctrine, which posits a constant sum of intracranial CSF, blood flow and brain tissue volumes. However, in recent decades, there has been a growing interest in exploring the dynamic interplay between these elements and the impact of external factors, such as daily changes in body position. CSF circulation in particular plays a crucial role in the context of neurodegeneration and dementia, since its dysfunction has been associated with impaired clearance mechanisms and accumulation of toxic substances. Despite the implementation of various invasive and non-invasive imaging techniques to investigate the intracranial hemodynamic or hydrodynamic properties, a comprehensive understanding of how all these elements interact and are influenced by body position remains wanted. Establishing a comprehensive overview of this topic is therefore crucial and could pave the way for alternative care approaches. In this review, we aim to summarize the existing understanding of intracranial hemodynamic and hydrodynamic properties, fundamental for brain homeostasis, along with factors known to influence their equilibrium. Special attention will be devoted to elucidating the effects of body position shifts, given their significance and remaining ambiguities. Furthermore, we will explore recent advancements in imaging techniques utilized for real time and non-invasive measurements of dynamic body fluid properties in-vivo.

IntroductionTranscranial direct current stimulation (tDCS) is a non-invasive neuromodulation technique with simultaneous (during stimulation) and cumulative effects (after repeated sessions) on blood flow and neuronal metabolism. These effects remain mostly unclear especially in multiple sclerosis (MS). This work aims to elucidate brain metabolic and hemodynamic underpinnings of tDCS and its potential therapeutic impact in MS patients using quantitative tDCS-MRI.MethodsMS participants (n = 20; age = 45.4 ± 12.3 years, 7 males) underwent 3 T MRI scans before and after 20 daily sessions of dorsolateral prefrontal cortex (DLFPC) tDCS (2.0 mA, left anodal) paired with adaptive cognitive training (aCT). During both visits, imaging measurements of cerebral blood flow (CBF), cerebral venous blood oxygenation (Yv) and calculated cerebral metabolic rate of oxygen (CMRO2) were obtained at pre-tDCS, during-tDCS and post-tDCS.ResultsAt baseline, significant increase from pre- to during-tDCS was observed in CMRO2 (7.6%; p = 0.002), CBF (11.0%; p

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.

Abstract 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

Background: The current understanding of the venous system in the hippocampus is mostly based on histological and autopsy studies.1 However, the main disadvantage is that it only reveals the anatomy of the vascular system at the post-mortem stage and lacks physiological aspects associated with neuronal metabolism. In vivo characterization of the venous system using susceptibility weighted imaging (SWI) at 7 T could provide valuable information on both venous anatomy and blood oxygen saturation, through high-resolution SWI venography2 and quantitative susceptibility mapping (QSM).3 In this study, we aim to elucidate the hierarchical network of the hippocampal venous system and then test the feasibility of using venous susceptibility to characterize venous oxygenation level changes related to neurodegeneration. Methods: Seven healthy volunteers were recruited for this study. We used high in-plane resolution of flow-compensated dual-echo gradient echo sequence (TE1/TE2/TR=7.5/15/22 ms, voxel size: 0.25*0.25*1 mm). SWI and QSM were then reconstructed using the iterative SWI and mapping (iterative SWIM) algorithm,3 as shown in Figure 1. Hippocampus masks were extracted from the T1-MPRAGE image, which was transformed to SWI space afterwards. To reduce the partial volume effect from the tissue-vessel boundary, we extract the venous susceptibility value from each voxel along the centerline of the vessels. Results: High-resolution in vivo mapping of hippocampal venous vasculature exhibits a high analogy to Duvernoy’s reference4 for hippocampal vascularization. As shown in Figure 1, there is a shape of venous arch near the fimbria of the hippocampus, and small veins extending through the arch are possibly the intrahippocampal veins. The intrahippocampal veins will eventually reach the inferior ventricular vein (IVV) (anteriorly) and medial atrial vein (MAV) (posteriorly), before joining the basal vein of Rosenthal (BVR). For venous susceptibility quantification, Figure 1 shows the representative color-coded QSM for centerline extraction on BVR. Conclusions: Our results showed improved visualization of the micro venous system in the hippocampus using high-resolution 7 T SWI data without the contrast agent.5 In summary, the characterization of venous QSM in major tributaries related to the hippocampus offers a novel perspective on oxygen utilization in the hippocampus, which may be useful for studying age-related dementia. We delineated the hierarchical network of the hippocampus venous system using SWI/QSM at 7 T and extract the venous density and venous susceptibility value in hippocampus-related small veins and major venous tributaries, as an overall measure for venous oxygenation level related to the hippocampus, which may be used as an early marker for hippocampal atrophy in Alzheimer’s disease.

Background. Cerebrospinal fluid (CSF) circulation consists of two components, a net flow and a pulsatile flow. CSF is generally believed to be produced through the ventricular choroid plexuses and absorbed in sites such as the subarachnoid granulations and nerve roots, contributing to the net flow. The pulsatile driving forces include cardiac vascular pulsation, respiration and muscular contraction.1 Measuring CSF flow in the upright posture is important because we spend most of our lifetime upright. Methods. Thirty asymptomatic volunteers (age: 22-72; 9 males, 21 females) were scanned in the upright seated and supine position on a 0.6 T multi-position MRI scanner (Fonar, New York, USA). CSF flow and spinal cord pulsation were imaged and quantified at the axial mid-C2 level with cine phase-contrast MRI. Results. In the upright posture, heart rate increased by 10%, and peak CSF diastolic flow decreased by 43% compared to the supine posture.2 In addition, the oscillatory volume of CSF exchanged between the spine and cranium decreased by 37% when going from supine to upright posture, consistent with a previous study.3 This could mean that the amount of time spent in different postures as we age may affect the efficiency of glymphatic brain waste clearance and development of neurodegenerative diseases. A less studied but diagnostically important aspect of CSF flow is the concomitant pulsation of spinal cord and central nervous system (CNS) tissue. For example, it is found that in Alzheimer’s Disease patients, the spinal cord at mid-C2 is pulsating much more in the mid to high frequency range (4 to 8 Hz) compared to normal older people in the supine posture. In the normal population, the mid-C2 spinal cord pulsates much less in the upright posture, with a 40% reduction of peak systolic velocity compared to the supine posture. Other postural differences include the more prominent appearance of nerve roots in the supine posture, shift of venous outflow from jugular veins to epidural/smaller veins, and the slimming of the neck when upright. It is also found that CSF flow is much more sensitive to aging in the upright than in the supine position. More specifically, as we age, heart rate change between postures diminishes and the upright peak systolic/peak-to-peak pressure gradient decreases. Since studies have shown that meditation can slow down brain aging, it would be beneficial to study its effect on CSF flow and the process of brain waste production and clearance. Conclusions. Besides delineating the many significant postural differences in CSF circulation, multi-position CSF imaging is also valuable in diagnosing various diseases such as Chiari malformation,4 Ehlers-Danlos syndrome and tethered cord syndrome in the lumbar spine. Often pathology that is not evident in the traditional supine imaging position can be visualized in other patient positions. Finally, a seminal study5 in rodents found that glymphatic transport is most efficient in the lateral recumbent position compared to supine or prone position, which concluded that posture must be considered in future diagnostic imaging procedures to assess CSF – interstitial fluid (ISF) transport in humans.

Background and PurposeThe 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.MethodsA 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.ResultsIndependent 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.ConclusionsVascular 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.