Mapping of iron deposition in conjunction with assessment of nerve fiber tract integrity in amyotrophic lateral sclerosis.

PURPOSE: To test if and where increased iron accumulation occurs in amyotrophic lateral sclerosis (ALS) by quantitative mapping of iron deposition and to relate these findings to white matter tract degeneration assessed by diffusion tensor imaging (DTI). MATERIALS AND METHODS: Fifteen patients with ALS and 15 age- and gender-matched controls underwent MRI of the brain to obtain R(2)* relaxation rate and DTI measurements, focusing on the corticospinal tract (CST) and on deep gray matter structures, using tract-based spatial statistics (TBSS). RESULTS: Compared with controls, ALS patients showed reduced fractional anisotropy values along the mesencephalic CST, suggesting disintegration of fiber tracts. A trend for R(2)* values to be elevated was found in the CST of ALS patients. Regarding other brain areas examined, increased R(2)* values in ALS patients were observed solely in the caudate nucleus. CONCLUSION: This study extends previous findings on fiber disorganization by additional quantitative evidence for increased iron deposition in closely localized regions along the CST in ALS patients. Longitudinal studies are needed to further explore the pathophysiologic and diagnostic implications of these findings.

3D cine displacement-encoded MRI of pulsatile brain motion.

Pulsatile brain motion is considered to be an important mechanical link between blood and cerebrospinal fluid (CSF) dynamics. Like many severe brain diseases, different types of hydrocephalus are associated with impairment of these dynamics. In this work a cine displacement-encoded imaging method employing stimulated echoes (DENSE) and a three-dimensional (3D) segmented echo-planar imaging (EPI) readout for brain motion measurements in all three spatial directions is presented. Displacement-encoded data sets of 12 healthy volunteers were analyzed with respect to reproducibility, periodicity, and intra- as well as intersubject physiological consistency. In addition, displacement values were compared with data derived from phase-contrast (PC) velocity measurements in a subset of all measured subjects. Using DENSE, displacements as low as 0.01 mm could be detected and observation of the 3D pulse pressure wave propagation was possible. Among other parameters, peak displacements in the central brain regions were measured: feet-head (FH): thalamus (0.13 +/- 0.01 mm); right-left (RL): thalamus (0.06 +/- 0.01 mm); and anterior-posterior (AP): caudate nucleus (0.05 +/- 0.01 mm).

Computational investigation of subject-specific cerebrospinal fluid flow in the third ventricle and aqueduct of Sylvius.

The cerebrospinal fluid flow in the third ventricle of the brain and the aqueduct of Sylvius was studied using computational fluid dynamics (CFD) based on subject-specific boundary conditions derived from magnetic resonance imaging (MRI) scans. The flow domain geometry was reconstructed from anatomical MRI scans by manual image segmentation. The movement of the domain boundary was derived from MRI brain motion scans. Velocimetric MRI scans were used to reconstruct the velocity field at the inferior end of the aqueduct of Sylvius based on the theory of pulsatile flow in pipes. A constant pressure boundary condition was assigned at the foramina of Monro. Three main flow features were observed: a fluid jet emerging from the aqueduct of Sylvius, a moderately mobile recirculation zone above the jet and a mobile recirculation below the jet. The flow in the entire domain was laminar with a maximum Reynolds number of 340 in the aqueduct. The findings demonstrate that by combining MRI scans and CFD simulations, subject-specific detailed quantitative information of the flow field in the third ventricle and the aqueduct of Sylvius can be obtained.

Age-specific characteristics and coupling of cerebral arterial inflow and cerebrospinal fluid dynamics.

The objective of this work is to quantify age-related differences in the characteristics and coupling of cerebral arterial inflow and cerebrospinal fluid (CSF) dynamics. To this end, 3T phase-contrast magnetic resonance imaging blood and CSF flow data of eleven young (24 ± 3 years) and eleven elderly subjects (70 ± 5 years) with a comparable sex-ratio were acquired. Flow waveforms and their frequency composition, transfer functions from blood to CSF flows and cross-correlations were analyzed. The magnitudes of the frequency components of CSF flow in the aqueduct differ significantly between the two age groups, as do the frequency components of the cervical spinal CSF and the arterial flows. The males' aqueductal CSF stroke volumes and average flow rates are significantly higher than those of the females. Transfer functions and cross-correlations between arterial blood and CSF flow reveal significant age-dependence of phase-shift between these, as do the waveforms of arterial blood, as well as cervical-spinal and aqueductal CSF flows. These findings accentuate the need for age- and sex-matched control groups for the evaluation of cerebral pathologies such as hydrocephalus.

Cerebrospinal fluid dynamics in the human cranial subarachnoid space: an overlooked mediator of cerebral disease. I. Computational model.

Abnormal cerebrospinal fluid (CSF) flow is suspected to be a contributor to the pathogenesis of neurodegenerative diseases such as Alzheimer's through the accumulation of toxic metabolites, and to the malfunction of intracranial pressure regulation, possibly through disruption of neuroendocrine communication. For the understanding of transport processes involved in either, knowledge of in vivo CSF dynamics is important. We present a three-dimensional, transient, subject-specific computational analysis of CSF flow in the human cranial subarachnoid space (SAS) based on in vivo magnetic resonance imaging. We observed large variations in the spatial distribution of flow velocities with a temporal peak of 5 cm s(-1) in the anterior SAS and less than 4 mm s(-1) in the superior part. This could reflect dissimilar flushing requirements of brain areas that may show differences in susceptibility to pathological CSF flow. Our methods can be used to compare the transport of metabolites and neuroendocrine substances in healthy and diseased brains.

Three-dimensional computational modeling of subject-specific cerebrospinal fluid flow in the subarachnoid space.

This study aims at investigating three-dimensional subject-specific cerebrospinal fluid (CSF) dynamics in the inferior cranial space, the superior spinal subarachnoid space (SAS), and the fourth cerebral ventricle using a combination of a finite-volume computational fluid dynamics (CFD) approach and magnetic resonance imaging (MRI) experiments. An anatomically accurate 3D model of the entire SAS of a healthy volunteer was reconstructed from high resolution T2 weighted MRI data. Subject-specific pulsatile velocity boundary conditions were imposed at planes in the pontine cistern, cerebellomedullary cistern, and in the spinal subarachnoid space. Velocimetric MRI was used to measure the velocity field at these boundaries. A constant pressure boundary condition was imposed at the interface between the aqueduct of Sylvius and the fourth ventricle. The morphology of the SAS with its complex trabecula structures was taken into account through a novel porous media model with anisotropic permeability. The governing equations were solved using finite-volume CFD. We observed a total pressure variation from -42 Pa to 40 Pa within one cardiac cycle in the investigated domain. Maximum CSF velocities of about 15 cms occurred in the inferior section of the aqueduct, 14 cms in the left foramen of Luschka, and 9 cms in the foramen of Magendie. Flow velocities in the right foramen of Luschka were found to be significantly lower than in the left, indicating three-dimensional brain asymmetries. The flow in the cerebellomedullary cistern was found to be relatively diffusive with a peak Reynolds number (Re)=72, while the flow in the pontine cistern was primarily convective with a peak Re=386. The net volumetric flow rate in the spinal canal was found to be negligible despite CSF oscillation with substantial amplitude with a maximum volumetric flow rate of 109 mlmin. The observed transient flow patterns indicate a compliant behavior of the cranial subarachnoid space. Still, the estimated deformations were small owing to the large parenchymal surface. We have integrated anatomic and velocimetric MRI data with computational fluid dynamics incorporating the porous SAS morphology for the subject-specific reconstruction of cerebrospinal fluid flow in the subarachnoid space. This model can be used as a basis for the development of computational tools, e.g., for the optimization of intrathecal drug delivery and computer-aided evaluation of cerebral pathologies such as syrinx development in syringomelia.

Assessment of human brain motion using CSPAMM.

PURPOSE: To quantify periodic displacement in the cranium using complementary spatial modulation of magnetization (CSPAMM) with harmonic phase (HARP) postprocessing. MATERIALS AND METHODS: CSPAMM tagging sequence with separate tag-line preparation in two orthogonal directions was applied on 10 healthy volunteers in combination with HARP for tissue displacement mapping. RESULTS: Important features of brain dynamics, such as caudal displacement amplitude and the time-to-peak of the pulse wave were derived for six regions in the brain. Peak displacement values amounted to 0.18+/-0.02 mm, 0.10+/-0.01 mm, 0.09+/-0.02 mm, and 0.04+/-0.01 mm for regions in the pons, cerebellum, corpus callosum (splenium), and frontal lobe, respectively. Displacement values of the pons differed significantly from all other regions measured. With the additional information of the time-to-peak measure all six regions except the corpus callosum (splenium) and cerebellum can be distinguished. The values found suggest that the pulse wave travels from the brain stem first occipitally and then to the frontal lobe, where peak values appear later and are significantly attenuated. CONCLUSION: Direct quantification of periodic caudal brain tissue displacement is feasible with the proposed method, and several brain regions can be distinguished through peak displacement and time-to-peak values.

Mixing and modes of mass transfer in the third cerebral ventricle: a computational analysis.

Anatomic, velocimetric, and brain motion MRI scans were combined with a computational fluid dynamics model to investigate cerebrospinal fluid (CSF) mixing in the third cerebral ventricle of a healthy male adult. It was found that advection dominates over diffusion in most of the third ventricle. Three zones where diffusion plays an important role in the mixing process were identified. One of these zones, consisting of recessus infundibulus, recessus opticus and the adjacent regions up to commissura anterior, is likely to exist in the general population. We hypothesize that this zone may act as a buffer to flatten concentration peaks of pituitary gland hormones released into the CSF of the third ventricle. We further hypothesize that this zone may facilitate the communication between hypothalamus and the pituitary gland through the third ventricle cerebrospinal fluid by prolonging residence times of the communicated hormones.

Noninvasive MRI assessment of intracranial compliance in idiopathic normal pressure hydrocephalus.

PURPOSE: To assess the state and dynamics of the intracranial system in idiopathic normal-pressure hydrocephalus (I-NPH), we determined intracranial compliance using magnetic resonance imaging (MRI). MATERIALS AND METHODS: The intracranial compliance index (ICCI), which was defined as the ratio of the peak-to-peak intracranial volume change (ICVC(p-p)) to the peak-to-peak cerebrospinal fluid (CSF) pressure gradient (PG(p-p)) during the cardiac cycle, was obtained from the net transcranial blood and CSF flow measured with phase-contrast (PC) cine MRI. ICCI was determined in patients with I-NPH (N = 7), brain atrophy, or asymptomatic ventricular dilation (VD) (N = 6), and in healthy volunteers (control group; N = 11). The changes in ICCI indices were also analyzed after a CSF tap test (N = 2). RESULTS: The ICCI in the I-NPH group was significantly lower than in the control and VD groups, whereas no difference was found between the control and VD groups. The ICVC(p-p) was also lower than in the control and VD groups. However, no significant difference was found in the PG(p-p) between groups. The ICCI increased after the tap test. CONCLUSION: Intracranial compliance analysis with MRI makes it possible to noninvasively obtain more detailed information of intracranial biomechanics in the I-NPH and to assist in the diagnosis of I-NPH.

Reconstruction of cerebrospinal fluid flow in the third ventricle based on MRI data.

A finite-volume model of the cerebrospinal fluid (CSF) system encompassing the third ventricle and the aqueduct of Sylvius was used to reconstruct CSF velocity and pressure fields based on MRI data. The flow domain geometry was obtained through segmentation of MRI brain anatomy scans. The movement of the domain walls was interpolated from brain motion MRI scans. A constant pressure boundary condition (BC) was specified at the foramina of Monro. A transient velocity BC reconstructed from velocimetric MRI scans was employed at the inferior end of the aqueduct of Sylvius. It could be shown that a combination of MRI scans and computational fluid dynamics (CFD) simulation can be used to reconstruct the flow field in the third ventricle. Pre-interventional knowledge of patient-specific CSF flow has the potential to improve neurosurgical interventions such as shunt placement in case of hydrocephalus.