CSF-filled Spaces Research Articles

Human intracranial pulsatility during the cardiac cycle: a computational modelling framework

BackgroundToday’s availability of medical imaging and computational resources set the scene for high-fidelity computational modelling of brain biomechanics. The brain and its environment feature a dynamic and complex interplay between the tissue, blood, cerebrospinal fluid (CSF) and interstitial fluid (ISF). Here, we design a computational platform for modelling and simulation of intracranial dynamics, and assess the models’ validity in terms of clinically relevant indicators of brain pulsatility. Focusing on the dynamic interaction between tissue motion and ISF/CSF flow, we treat the pulsatile cerebral blood flow as a prescribed input of the model.MethodsWe develop finite element models of cardiac-induced fully coupled pulsatile CSF flow and tissue motion in the human brain environment. The three-dimensional model geometry is derived from magnetic resonance images (MRI) and features a high level of detail including the brain tissue, the ventricular system, and the cranial subarachnoid space (SAS). We model the brain parenchyma at the organ-scale as an elastic medium permeated by an extracellular fluid network and describe flow of CSF in the SAS and ventricles as viscous fluid movement. Representing vascular expansion during the cardiac cycle, a prescribed pulsatile net blood flow distributed over the brain parenchyma acts as the driver of motion. Additionally, we investigate the effect of model variations on a set of clinically relevant quantities of interest.ResultsOur model predicts a complex interplay between the CSF-filled spaces and poroelastic parenchyma in terms of ICP, CSF flow, and parenchymal displacements. Variations in the ICP are dominated by their temporal amplitude, but with small spatial variations in both the CSF-filled spaces and the parenchyma. Induced by ICP differences, we find substantial ventricular and cranial-spinal CSF flow, some flow in the cranial SAS, and small pulsatile ISF velocities in the brain parenchyma. Moreover, the model predicts a funnel-shaped deformation of parenchymal tissue in dorsal direction at the beginning of the cardiac cycle.ConclusionsOur model accurately depicts the complex interplay of ICP, CSF flow and brain tissue movement and is well-aligned with clinical observations. It offers a qualitative and quantitative platform for detailed investigation of coupled intracranial dynamics and interplay, both under physiological and pathophysiological conditions.

Magnetic resonance cisternography

Conventional MRI can be insufficient to depict certain pathologies of the cerebrospinal fluid (CSF)-filled spaces. 3-D T2-weighted sequences and phase-contrast imaging have ahigh sensitivity for pathologies of the CSF-filled spaces, but are susceptible to artifacts in some cases. Magnetic resonance (MR) cisternography directly depicts the connection between CSF-filled spaces.

Visualization of cerebrospinal fluid-filled spaces in the cavernous sinus using magnetic resonance imaging

The cavernous sinus (CS) has been extensively studied and is commonly acknowledged as a dural venous sinus. There have been no reports documenting cerebrospinal fluid (CSF)-filled spaces in the CS. Here, we explore such structures in the CS using magnetic resonance imaging (MRI). A total of 183 patients underwent T2-weighted or constructive interference steady-state (CISS) sequence MRI. Imaging data from coronal sections were analyzed. Of the 183 patients, 26.8% had CSF-filled spaces in the CS. These spaces appeared to communicate with the suprasellar cistern through dural defects found in the superior wall of the CS, and also appeared to surround the cavernous portion of the internal carotid artery (ICc) and pituitary gland, and further be adjacent to the oculomotor and trigeminal cisterns. Dural defects were identified in 81.6% of patients, with CSF-filled spaces adjacent to the oculomotor and trigeminal cisterns found in 81.6% and 12.2% of patients, respectively. The distribution of these spaces could be classified into four types based on their topographical relationships with the ICc, namely the circumferential, medial, lateral, and superior types. The circumferential and medial types were the most frequently found and comprised >80% on both sides. The CS may involve CSF-filled spaces in physiological conditions that are formed through dural defects in the superior wall and adjacent cranial nerve cisterns. These findings are critical when considering approaches to the CS, modes of lateral extension of pituitary tumors, and CSF dynamics in the CS.

Delivery of therapeutic protein for prevention of neurodegenerative changes: Comparison of different CSF-delivery methods

Injection of lysosomal enzyme into cisternal or ventricular cerebrospinal fluid (CSF) has been carried out in 11 lysosomal storage disorder models, with each study demonstrating reductions in primary substrate and secondary neuropathological changes, and several reports of improved neurological function. Whilst acute studies in mucopolysaccharidosis (MPS) type II mice revealed that intrathecally-delivered enzyme (into thoraco-lumbar CSF) accesses the brain, the impact of longer-term treatment of affected subjects via this route is unknown. This approach is presently being utilized to treat children with MPS types I, II and III. Our aim was to determine the efficacy of repeated intrathecal injection of recombinant human sulfamidase (rhSGSH) on pathological changes in the MPS IIIA dog brain. The outcomes were compared with those in dogs treated via intra-cisternal or ventricular routes. Control dogs received buffer or no treatment. Significant reductions in primary/secondary substrate levels in brain were observed in dogs treated via all routes, although the extent of the reduction differed regionally. Treatment via all CSF access points resulted in large reductions in microgliosis in superficial cerebral cortex, but only ventricular injection enabled amelioration in deep cerebral cortex. Formation of glutamic acid decarboxylase-positive axonal spheroids in deep cerebellar nuclei was prevented by treatment delivered via any route. Anti-rhSGSH antibodies in the sera of some dogs did not reduce therapeutic efficacy. Our data indicates the capacity of intra-spinal CSF-injected rhSGSH to circulate within CSF-filled spaces, penetrate into brain and mediate a significant reduction in substrate accumulation and secondary pathology in the MPS IIIA dog brain.

Variation in longitudinal trajectories of regional brain volumes of healthy men and women (ages 10 to 85years) measured with atlas-based parcellation of MRI

Numerous cross-sectional MRI studies have characterized age-related differences in regional brain volumes that differ with structure and tissue type. The extent to which cross-sectional assumptions about change are accurate depictions of actual longitudinal measurement remains controversial. Even longitudinal studies can be limited by the age range of participants, sex distribution of the samples, and scan intervals. To address these issues, we calculated trajectories of regional brain volume changes from T1-weighted (SPGR) MRI data, quantified with our automated, unsupervised SRI24 atlas-based registration and parcellation method. Longitudinal MRIs were acquired at 3T in 17 boys and 12 girls, age 10 to 14 years, and 41 men and 41 women, age 20 to 85 years at first scan. Application of a regression-based correction function permitted merging of data acquired at 3T field strength with data acquired at 1.5T from additional subjects, thereby expanding the sample to a total of 55 men and 67 women, age 20 to 85 years at first scan. Adjustment for individual supratentorial volume removed regional volume differences between men and women due to sex-related differences in head size. Individual trajectories were computed from data collected on 2 to 6 MRIs at a single field strength over a ~1 to 8 year interval. Using linear mixed-effects models, the pattern of trajectories over age indicated: rises in ventricular and Sylvian fissure volumes, with older individuals showing faster increases than younger ones; declines in selective cortical volumes with faster tissue shrinkage in older than younger individuals; little effect of aging on volume of the corpus callosum; more rapid expansion of CSF-filled spaces in men than women after age 60 years; and evidence for continued growth in central white matter through early adulthood with accelerated decline in senescence greater in men than women.

Brain leukocyte infiltration initiated by peripheral inflammation or experimental autoimmune encephalomyelitis occurs through pathways connected to the CSF-filled compartments of the forebrain and midbrain

BackgroundCerebrospinal fluid (CSF) has been considered as a preferential pathway of circulation for immune cells during neuroimmune surveillance. In order to evaluate the involvement of CSF-filled spaces in the pathogenesis of experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis, we performed a time-course analysis of immune cell association with the CSF-containing ventricles, velae, and cisterns in two active models of this disease.MethodsGuinea-pig spinal cord homogenate-induced EAE in rat and myelin oligodendrocyte glycoprotein-induced EAE in mouse were used. Leukocyte distribution and phenotypes were investigated by immunohistochemistry in serial sections of brain areas of interest, as well as in CSF withdrawn from rat. Immune cells associated with the choroid plexuses were quantified.ResultsFreund’s adjuvant-induced peripheral inflammation in the absence of brain antigen led to a subtle but definite increase in the number of myeloid cells in the extraventricular CSF spaces. In both rats and mice, EAE was characterized by a sustained and initial infiltration of lymphocytes and monocytes within forebrain/midbrain fluid-filled compartments such as the velum interpositum and ambient cisterns, and certain basal cisterns. Leukocytes further infiltrated periventricular and pericisternal parenchymal areas, along perivascular spaces or following a downward CSF-to-tissue gradient. Cells quantified in CSF sampled from rats included lymphocytes and neutrophils. The distinctive pattern of cell distribution suggests that both the choroid plexus and the vessels lying in the velae and cisterns are gates for early leukocyte entry in the central nervous system. B-cell infiltration observed in the mouse model was restricted to CSF-filled extraventricular compartments.ConclusionThese results identified distinctive velae and cisterns of the forebrain and midbrain as preferential sites of immune cell homing following peripheral and early central inflammation and point to a role of CSF in directing brain invasion by immune cells during EAE.

Combining atlas-based parcellation of regional brain data acquired across scanners at 1.5T and 3.0T field strengths

Longitudinal brain morphometric studies designed for data acquisition at a single MRI field strength can be seriously limited by system replacements from lower to higher field strength. Merging data across field strengths has not been endorsed for a variety of reasons, yet the ability to combine such data would broaden longitudinal investigations. To determine whether structural T1-weighted MRI data acquired across MR field strengths could be merged, parcellations of archival SPGR data acquired in 114 individuals at 1.5 T and at 3.0 T within 3 weeks of each other were compared. The first set of analyses examined 1) the correspondence between regional tissue volumes derived from data collected at 1.5 T and 3.0 T and 2) whether there were systematic differences for which a correction factor could be determined and applied to improve measurement agreement. Comparability of regional volume determination at 1.5 T and 3.0 T was assessed with intraclass correlation (ICC) computed on volumes derived from the automated and unsupervised SRI24 atlas registration and parcellation method. A second set of analyses measured the reliability of the registration and quantification using the same approach on longitudinal data acquired in 69 healthy adults at a single field strength, 1.5 T, at an interval < 2 years. The mainstay of the analyses was based on the SRI24 method; to examine the potential of merging data across field strengths and across image analysis packages, a secondary set of analyses used FreeSurfer instead of the SRI24 method. For both methods, a regression-based linear correction function significantly improved correspondence. The results indicated high correspondence between most selected cortical, subcortical, and CSF-filled spaces; correspondence was lowest in the globus pallidus, a region rich in iron, which in turn has a considerable field-dependent effect on signal intensity. Thus, the application of a regression-based correction function that improved the correspondence in regional volume estimations argues well for the proposition that selected T1-weighted regional anatomical brain data can be reliably combined across 1.5 T and 3.0 T field strengths with the application of an appropriate correction procedure.

Reduced Brain Size of Very Preterm Infants at Term Equivalent Age Can be Estimated using Cerebral Ultrasound Measurements

Objective: To compare brain size between very preterm infants at term equivalent age (TEA) and term neonates using cerebral ultrasound (cUS) measurements and occipito-frontal head circumference (OFHC).Methods: We assessed prospectively a cohort of 88 preterm infants < 32 weeks gestation at TEA (mean postmenstrual age (PMA) 40.6 weeks) and 61 term controls (mean postnatal day 5.29, mean PMA 39.9 weeks). Infants with birth weight < 10th centile or major scan abnormality were excluded. A single observer made cUS measurements of biparietal diameter, brain structures, ventricles, extracerebral spaces and also OFHC. A mathematical model was built to estimate from the cUS measurements and OFHC the axial area of head, CSF-filled spaces and brain tissue. Statistical comparison was performed using independent samples t-test or Mann-Whitney test when appropriate and corrected for PMA at scan.Results: Preterms had a larger OFHC at TEA than controls (p=0.000), but total axial cranial area was similar (p=0.705). However, the CSF-filled spaces were significantly larger in preterm (p=0.000) than controls and estimated brain area in preterms was significantly smaller (p=0.000).Conclusions: Our data shows that estimated brain area in an axial plane is smaller in preterms, supporting the view that extra-uterine preterm brain growth is compromised, even in the absence of overt lesions. Preterm children without major lesions but smaller brains may be more at risk of neurodevelopmental problems (Horsch 2005) and our data suggests that cUS measurements may be useful in their identification. Long-term follow-up is being undertaken in this cohort.

Cerebrospinal Fluid Flow in the Normal and Hydrocephalic Human Brain

Advances in magnetic resonance (MR) imaging techniques enable the accurate measurements of cerebrospinal fluid (CSF) flow in the human brain. In addition, image reconstruction tools facilitate the collection of patient-specific brain geometry data such as the exact dimensions of the ventricular and subarachnoidal spaces (SAS) as well as the computer-aided reconstruction of the CSF-filled spaces. The solution of the conservation of CSF mass and momentum balances over a finite computational mesh obtained from the MR images predict the patients' CSF flow and pressure field. Advanced image reconstruction tools used in conjunction with first principles of fluid mechanics allow an accurate verification of the CSF flow patters for individual patients. This paper presents a detailed analysis of pulsatile CSF flow and pressure dynamics in a normal and hydrocephalic patient. Experimental CSF flow measurements and computational results of flow and pressure fields in the ventricular system, the SAS and brain parenchyma are presented. The pulsating CSF motion is explored in normal and pathological conditions of communicating hydrocephalus. This paper predicts small transmantle pressure differences between lateral ventricles and SASs (approximately 10 Pa). The transmantle pressure between ventricles and SAS remains small even in the hydrocephalic patient (approximately 30 Pa), but the ICP pulsatility increases by a factor of four. The computational fluid dynamics (CFD) results of the predicted CSF flow velocities are in good agreement with Cine MRI measurements. Differences between the predicted and observed CSF flow velocities in the prepontine area point towards complex brain-CSF interactions. The paper presents the complete computational model to predict the pulsatile CSF flow in the cranial cavity.

Study of the effect of CSF suppression on white matter diffusion anisotropy mapping of healthy human brain.

Healthy human brain diffusion anisotropy maps derived from standard spin echo diffusion tensor imaging (DTI) were compared with those using fluid-attenuated inversion recovery (FLAIR) preparation prior to DTI to null the signal from cerebrospinal fluid (CSF). Consistent comparisons entailed development of DTI postprocessing methods, image masking based on fitting quality, and an objective region-of-interest-based method for assessment of white matter extent. FLAIR DTI achieved an extended delineation of major white-matter tracts (genu, splenium, and body of the corpus callosum) close to large CSF-filled spaces (lateral ventricles), but did not affect representation of tracts remote from CSF (internal and external capsules and coronal radiation). This result, which was detectable qualitatively (visual inspection), was verified quantitatively by analyses of the relative anisotropy (RA) distribution over white matter structures for 11 subjects. FLAIR DTI thus suppresses the CSF signal that otherwise masks underlying anisotropic parenchymal tissue through partial volume averaging.

Pressure compensation in shunt-dependent hydrocephalus with CSF shunt malfunction

This study is a retrospective analysis of intracranial pressure (ICP) and cerebral perfusion pressure (CPP) data from 56 children with active hydrocephalus and cerebrospinal fluid (CSF) shunt malfunction. The pressures were measured from a separately sited CSF access device placed in the frontal horn of the lateral ventricle. Of the patients, 79% had an elevated ICP (mean 20+/-12 mmHg). A subgroup of patients demonstrated ten different forms of CSF-filled swelling. This group had significantly lower ICP recordings (P=0.000075) with a mean ICP of 8.5 mmHg compared with the remainder (22.9 mmHg). This pressure 'compensation' was because of additional nonphysiological accommodation of CSF volume. Overall the CPP was normal in 35% of cases despite normal ICP occurring in only 11% of cases. The CPPs were not significantly different in those with and without compensation. Measurement of ICP may not always be a reliable indicator of shunt malfunction in shunt-dependent children who present with compensatory CSF-filled spaces.

MR imaging of normal rat brain at 0.35 T and correlated histology

A custom-built small-animal transceiver was used for in vivo imaging of normal rat brain at 0.35 T, with the objective of identifying anatomic components by comparison of images with corresponding histologic sections. The cerebrum, cerebellum, brain stem, ventricles, hippocampus, and subarachnoid space were identified and cerebrospinal fluid (CSF) was differentiated from gray matter and white matter on coronal and transaxial magnetic resonance (MR) images. These images compare favorably with those obtained by others at higher field strengths in regard to delineating major neuroanatomic structures. It is concluded that this technique will be useful for investigating small-animal models of human neurologic disease involving morphologic and morphometric changes in gray matter, white matter, and CSF-filled spaces.