An in vitro experimental investigation of oscillatory flow in the cerebral aqueduct.

This in vitro study aims at clarifying the relation between the oscillatory flow of cerebrospinal fluid (CSF) in the cerebral aqueduct, a narrow conduit connecting the third and fourth ventricles, and the corresponding interventricular pressure difference. Dimensional analysis is used in designing an anatomically correct scaled model of the aqueduct flow, with physical similarity maintained by adjusting the flow frequency and the properties of the working fluid. The time-varying pressure difference across the aqueduct corresponding to a given oscillatory flow rate is measured in parametric ranges covering the range of flow conditions commonly encountered in healthy subjects. Parametric dependences are delineated for the time-averaged pressure fluctuations and for the phase lag between the transaqueductal pressure difference and the flow rate, both having clinical relevance. The results are validated through comparisons with predictions obtained with a previously derived computational model. The parametric quantification in this study enables the derivation of a simple formula for the relation between the transaqueductal pressure and the stroke volume. This relationship can be useful in the quantification of transmantle pressure differences based on non-invasive magnetic-resonance-velocimetry measurements of aqueduct flow for investigation of CSF-related disorders.

An analytic model for the flow induced in syringomyelia cavities.

A simple two-dimensional fluid-structure-interaction problem, involving viscous oscillatory flow in a channel separated by an elastic membrane from a fluid-filled slender cavity, is analyzed to shed light on the flow dynamics pertaining to syringomyelia, a neurological disorder characterized by the appearance of a large tubular cavity (syrinx) within the spinal cord. The focus is on configurations in which the velocity induced in the cavity, representing the syrinx, is comparable to that found in the channel, representing the subarachnoid space surrounding the spinal cord, both flows being coupled through a linear elastic equation describing the membrane deformation. An asymptotic analysis for small stroke lengths leads to closed-form expressions for the leading-order oscillatory flow, and also for the stationary flow associated with the first-order corrections, the latter involving a steady distribution of transmembrane pressure. The magnitude of the induced flow is found to depend strongly on the frequency, with the result that for channel flow rates of non-sinusoidal waveform, as those found in the spinal canal, higher harmonics can dominate the sloshing motion in the cavity, in agreement with previous in vivo observations. Under some conditions, the cycle-averaged transmembrane pressure, also showing a marked dependence on the frequency, changes sign on increasing the cavity transverse dimension (i.e. orthogonal to the cord axis), underscoring the importance of cavity size in connection with the underlying hydrodynamics. The analytic results presented here can be instrumental in guiding future numerical investigations, needed to clarify the pathogenesis of syringomyelia cavities.

A one-dimensional model for the pulsating flow of cerebrospinal fluid in the spinal canal.

The monitoring of intracranial pressure (ICP) fluctuations, which is needed in the context of a number of neurological diseases, requires the insertion of pressure sensors, an invasive procedure with considerable risk factors. Intracranial pressure fluctuations drive the wave-like pulsatile motion of cerebrospinal fluid (CSF) along the compliant spinal canal. Systematically derived simplified models relating the ICP fluctuations with the resulting CSF flow rate can be useful in enabling indirect evaluations of the former from non-invasive magnetic resonance imaging (MRI) measurements of the latter. As a preliminary step in enabling these predictive efforts, a model is developed here for the pulsating viscous motion of CSF in the spinal canal, assumed to be a linearly elastic compliant tube of slowly varying section, with a Darcy pressure-loss term included to model the fluid resistance introduced by the trabeculae, which are thin collagen-reinforced columns that form a web-like structure stretching across the spinal canal. Use of Fourier-series expansions enables predictions of CSF flow rate for realistic anharmonic ICP fluctuations. The flow rate predicted using a representative ICP waveform together with a realistic canal anatomy is seen to compare favourably with in vivo phase-contrast MRI measurements at multiple sections along the spinal canal. The results indicate that the proposed model, involving a limited number of parameters, can serve as a basis for future quantitative analyses targeting predictions of ICP temporal fluctuations based on MRI measurements of spinal-canal anatomy and CSF flow rate.

Effect of Normal Breathing on the Movement of CSF in the Spinal Subarachnoid Space.

BACKGROUND AND PURPOSE: Forced respirations reportedly have an effect on CSF movement in the spinal canal. We studied respiratory-related CSF motion during normal respiration. MATERIALS AND METHODS: Six healthy subjects breathed at their normal rate with a visual guide to ensure an unchanging rhythm. Respiratory-gated phase-contrast MR flow images were acquired at 5 selected axial planes along the spine. At each spinal level, we computed the flow rate voxelwise in the spinal canal, together with the associated stroke volume. From these data, we computed the periodic volume changes of spinal segments. A phantom was used to quantify the effect of respiration-related magnetic susceptibility changes on the velocity data measured. RESULTS: At each level, CSF moved cephalad during inhalation and caudad during expiration. While the general pattern of fluid movement was the same in the 6 subjects, the flow rates, stroke volumes, and spine segment volume changes varied among subjects. Peak flow rates ranged from 0.60 to 1.59 mL/s in the cervical region, 0.46 to 3.17 mL/s in the thoracic region, and 0.75 to 3.64 mL/s in the lumbar region. The differences in flow rates along the canal yielded cyclic volume variations of spine segments that were largest in the lumbar spine, ranging from 0.76 to 3.07 mL among subjects. In the phantom study, flow velocities oscillated periodically during the respiratory cycle by up to 0.02 cm/s or 0.5%. CONCLUSIONS: Respiratory-gated measurements of the CSF motion in the spinal canal showed cyclic oscillatory movements of spinal fluid correlated to the breathing pattern.

Transmantle Pressure Computed from MR Imaging Measurements of Aqueduct Flow and Dimensions.

BACKGROUND AND PURPOSE: Measuring transmantle pressure, the instantaneous pressure difference between the lateral ventricles and the cranial subarachnoid space, by intracranial pressure sensors has limitations. The aim of this study was to compute transmantle pressure noninvasively with a novel nondimensional fluid mechanics model in volunteers and to identify differences related to age and aqueductal dimensions. MATERIALS AND METHODS: Brain MR images including cardiac-gated 2D phase-contrast MR imaging and fast-spoiled gradient recalled imaging were obtained in 77 volunteers ranging in age from 25-92 years of age. Transmantle pressure was computed during the cardiac cycle with a fluid mechanics model from the measured aqueductal flow rate, stroke volume, aqueductal length and cross-sectional area, and heart rate. Peak pressures during caudal and rostral aqueductal flow were tabulated. The computed transmantle pressure, aqueductal dimensions, and stroke volume were estimated, and the differences due to sex and age were calculated and tested for significance. RESULTS: Peak transmantle pressure was calculated with the nondimensional averaged 14.4 (SD, 6.5) Pa during caudal flow and 6.9 (SD, 2.8) Pa during rostral flow. It did not differ significantly between men and women or correlate significantly with heart rate. Peak transmantle pressure increased with age and correlated with aqueductal dimensions and stroke volume. CONCLUSIONS: The nondimensional fluid mechanics model for computing transmantle pressure detected changes in pressure related to age and aqueductal dimensions. This novel methodology can be easily used to investigate the clinical relevance of the transmantle pressure in normal pressure hydrocephalus, pediatric communicating hydrocephalus, and other CSF disorders.

Subject-Specific Studies of CSF Bulk Flow Patterns in the Spinal Canal: Implications for the Dispersion of Solute Particles in Intrathecal Drug Delivery.

BACKGROUND AND PURPOSE: Recent flow dynamics studies have shown that the eccentricity of the spinal cord affects the magnitude and characteristics of the slow bulk motion of CSF in the spinal subarachnoid space, which is an important variable in solute transport along the spinal canal. The goal of this study was to investigate how anatomic differences among subjects affect this bulk flow. MATERIALS AND METHODS: T2-weighted spinal images were obtained in 4 subjects and repeated in 1 subject after repositioning. CSF velocity was calculated from phase-contrast MR images for 7 equally spaced levels along the length of the spine. This information was input into a 2-time-scale asymptotic analysis of the Navier-Stokes and concentration equations to calculate the short- and long-term CSF flow in the spinal subarachnoid space. Bulk flow streamlines were shown for each subject and position and inspected for differences in patterns. RESULTS: The 4 subjects had variable degrees of lordosis and kyphosis. Repositioning in 1 subject changed the degree of cervical lordosis and thoracic kyphosis. The streamlines of bulk flow show the existence of distinct regions where the fluid particles flow in circular patterns. The location and interconnectivity of these recirculating regions varied among individuals and different positions. CONCLUSIONS: Lordosis, kyphosis, and spinal cord eccentricity in the healthy human spine result in subject-specific patterns of bulk flow recirculating regions. The extent of the interconnectivity of the streamlines among these recirculating regions is fundamental in determining the long-term transport of solute particles along the spinal canal.

Fluid dynamics in syringomyelia cavities: Effects of heart rate, CSF velocity, CSF velocity waveform and craniovertebral decompression.

Purpose How fluid moves during the cardiac cycle within a syrinx may affect its development. We measured syrinx fluid velocities before and after craniovertebral decompression in a patient and simulated syrinx fluid velocities for different heart rates, syrinx sizes and cerebrospinal fluid (CSF) flow velocities in a model of syringomyelia. Materials and methods With phase-contrast magnetic resonance we measured CSF and syrinx fluid velocities in a Chiari patient before and after craniovertebral decompression. With an idealized two-dimensional model of the subarachnoid space (SAS), cord and syrinx, we simulated fluid movement in the SAS and syrinx with the Navier-Stokes equations for different heart rates, inlet velocities and syrinx diameters. Results In the patient, fluid oscillated in the syrinx at 200 to 210 cycles per minute before and after craniovertebral decompression. Velocities peaked at 3.6 and 2.0 cm per second respectively in the SAS and the syrinx before surgery and at 2.7 and 1.5 cm per second after surgery. In the model, syrinx velocity varied between 0.91 and 12.70 cm per second. Increasing CSF inlet velocities from 1.56 to 4.69 cm per second increased peak syrinx fluid velocities in the syrinx by 151% to 299% for the three cycle rates. Increasing cycle rates from 60 to 120 cpm increased peak syrinx velocities by 160% to 312% for the three inlet velocities. Peak velocities changed inconsistently with syrinx size. Conclusions CSF velocity, heart rate and syrinx diameter affect syrinx fluid velocities, but not the frequency of syrinx fluid oscillation. Craniovertebral decompression decreases both CSF and syrinx fluid velocities.

Changes in T2 relaxation times associated with maturation of the human intervertebral disk.

BACKGROUND AND PURPOSE: By calculating T2 relaxation times for intervertebral disks, we tested the hypothesis that disk water concentration increases between the first and second decades of life. MATERIALS AND METHODS: In subjects younger than 10 years old (group 1) and subjects between 19 and 20 years old (group 2), a sagittal MR image of the lumbar spine was obtained with a modified 3D fast spin-echo (FSE) multi-echo sequence. T2 relaxation times for each voxel were calculated by fitting a logarithmic regression to the signal intensity in images at 16 different echo times. T2 times were averaged for each spinal disk in each group and differences tested for statistical significance by analysis of variance (ANOVA). T2 times along the vertical axis of the disk at the midline were plotted and inspected for evidence of a central lower signal intensity region (CLSIR) in the 2 groups. We tested the differences between groups for significance with the Student t test. RESULTS: Maps of T2 relaxation times showed different patterns in groups 1 and 2. The mean T2 relaxation times in each disk level in group 1 ranged from 74-95 ms and in group 2, from 91-119 ms. Differences between the 2 groups were significant (P<.001, ANOVA, P=.0002, Student t test of means); differences between levels were not. In group 2, development of a CLSIR was significantly more common than in group 1 (P=.0001, Student t test). CONCLUSIONS: T2 increases in the intervertebral disk between the first and second decades of life.

Physiologic and anatomic assessment of a canine carotid artery stenosis model utilizing phase contrast with vastly undersampled isotropic projection imaging.

BACKGROUND AND PURPOSE: Noninvasive assessment of the hemodynamic significance of carotid stenosis is often performed with MR angiography and supplemented with carotid Doppler sonography. Phase contrast with vastly undersampled isotropic projection reconstruction (PC-VIPR), a novel MR imaging technique, accelerates phase-contrast MR flow imaging and provides both images of the vessels and measurements of blood-flow velocities. For this study, we determined the accuracy of PC-VIPR blood-flow velocity measurements to determine pressure gradients across an experimental carotid stenosis. MATERIALS AND METHODS: A focal stenosis was surgically created in each common carotid artery of 6 canines. Digital subtraction angiography (DSA) was performed, and the degree of stenosis was determined using the North American Symptomatic Carotid Endarterectomy Trial methodology. A microcatheter was positioned in the carotid artery proximal and distal to the stenosis, and pressures were measured in the vessel through the catheter. PC-VIPR was then performed on a 1.5T MR imaging scanner with parameters producing 0.8-mm isotropic voxel resolution. From the velocity measurements, pressure gradients were calculated from the Navier-Stokes relationship to compare with the pressures measured by a catheter. RESULTS: Carotid stenoses in the 50%-85% range were produced in the 12 arteries. Pressure gradients across the stenoses ranged from 6 to 26 mm Hg. The pressure gradient calculated from the PC-VIPR data correlated (r = 0.91, P < .0001) with the actual pressure measurements. CONCLUSION: With PC-VIPR, a novel MR imaging technique, the hemodynamic effect of a stenosis on flow and pressure can be evaluated.

Recording CSF pressure with a transducer-tipped wire in an animal model of Chiari I.

In dogs, a wire with a pressure-sensitive transducer was inserted percutaneously into the subarachnoid space and manipulated under fluoroscopic monitoring in the posterior fossa or upper cervical spinal canal. Pressure recordings from the wire showed fluctuations in pressure corresponding to the cardiac cycle. When a balloon was distended in the foramen magnum, maximum and minimum pressures increased. Continuous monitoring of CSF pressure remote from the site of cannulation was feasible with a wire-based pressure transducer.

The value of T2 relaxation times to characterize lumbar intervertebral disks: preliminary results.

BACKGROUND AND PURPOSE: The present standard for staging intervertebral disk degeneration is a discrete scale, consisting usually of 5 stages. The purpose of this pilot study was to investigate the use of T2 measurements as a continuous measure of intervertebral disk degeneration. METHODS: We obtained images in 5 volunteers with a 3D fast spin-echo sequence modified for the purpose of calculating T2 relaxation times from multiple echoes in the echo train. Disks were classified on the basis of conventional criteria into one of the 5 stages of disk degeneration. Average T2 values were calculated for stage II, III, and V disks, which were identified in the volunteers. Differences between the disk levels were analyzed with analysis of variance and differences between stages tested with a Student t test with significance set at the 0.01 level. RESULTS: In the 5 volunteers, 20 stage II, 4 stage III, and a single stage V disk were found. Contour plots showed the highest T2 values in the nucleus pulposus near the vertebral endplates and lower T2 values in the intranuclear cleft region and peripheral annulus fibrosus. Average T2 values were significantly lower in the type III and V disks than in the normal disks. CONCLUSIONS: The study suggests that intervertebral disks can be characterized and classified accurately by means of T2 values. More studies are warranted to determine the range of T2 values for normal disks.

The Cervical Spinal Canal Tapers Differently in Patients with Chiari I with and without Syringomyelia.

BACKGROUND AND PURPOSE: The cause of syringomyelia in patients with Chiari I remains uncertain. Cervical spine anatomy modifies CSF velocities, flow patterns, and pressure gradients, which may affect the spinal cord. We tested the hypothesis that cervical spinal anatomy differs between Chiari I patients with and without syringomyelia. MATERIALS AND METHODS: We identified consecutive patients with Chiari I at 3 institutions and divided them into groups with and without syringomyelia. Five readers measured anteroposterior cervical spinal diameters, tonsillar herniation, and syrinx dimensions on cervical MR images. Taper ratios for C1-C7, C1-C4, and C4-C7 spinal segments were calculated by linear least squares fitting to the appropriate spinal canal diameters. Mean taper ratios and tonsillar herniation for groups were compared and tested for statistical significance with a Kruskal-Wallis test. Inter- and intrareader agreement and correlations in the data were measured. RESULTS: One hundred fifty patients were included, of which 49 had syringomyelia. C1-C7 taper ratios were smaller and C4-C7 taper ratios greater for patients with syringomyelia than for those without it. C1-C4 taper ratios did not differ significantly between groups. Patients with syringomyelia had, on average, greater tonsillar herniation than those without a syrinx. However, C4-C7 taper ratios were steeper, for all degrees of tonsil herniation, in patients with syringomyelia. Differences among readers did not exceed differences among patient groups. CONCLUSIONS: The tapering of the lower cervical spine may contribute to the development of syringomyelia in patients with Chiari I.

Hypercapnia reversibly suppresses low-frequency fluctuations in the human motor cortex during rest using echo-planar MRI.

Using magnetic resonance (MR) echo-planar imaging (EPI), we recently demonstrated the presence of low-frequency fluctuations (< 0.1 Hz) in MR signal intensity from the resting human brain that have a high degree of temporal correlation (p < 10(-3)) within and across associated regions of the sensorimotor cortex. These fluctuations in MR signal intensity are believed to arise from fluctuations in capillary blood flow and oxygenation. A substantial overlap between the activation map generated by bilateral finger tapping and temporally-correlated voxels from the sensorimotor cortex obtained during rest was observed. In the work reported here, we investigated whether respiratory hypercapnia, which is known to suspend spontaneous oscillations in regional cerebral blood flow, influences these low-frequency fluctuations. The magnitude of low-frequency fluctuations was reversibly diminished during hypercapnia, resulting in a substantial decrease of the temporal correlation both within and across contralateral hemispheres of the sensorimotor cortex. After the breathing mixture was returned to ambient air, the magnitude and spatial extent of the temporal correlation of low-frequency fluctuations returned to normal. Results of this study support the hypothesis that low-frequency physiological fluctuations observed by MR in the human cortex and spontaneous flow oscillations observed in early studies by laser-Doppler flowmetry (LDF) in the cortex of the rat are identical and are secondary to fluctuations in neuronal activity.

Comparison of single-photon emission computed tomography with [123I]iodoamphetamine and xenon-enhanced computed tomography for assessing regional cerebral blood flow.

Regional CBF (rCBF) images obtained from xenon-enhanced computed tomography (XeCT) and single-photon emission computed tomography (SPECT) with N-isopropyl-p-[123I]iodoamphetamine (IMP) done with a rotating gamma-camera were compared in nine patients. Both XeCT and SPECT/IMP demonstrated flow abnormalities at all sites of infarction identified by CT, while detecting reduced rCBF in areas normal by CT in eight of the nine patients. All areas that were abnormal on XeCT were abnormal on the comparable SPECT/IMP images. The major advantages of XeCT are its greater resolution and potential for noninvasive quantitation of rCBF, while the major advantage of SPECT/IMP is its visualization of the entire brain on transverse, coronal, and sagittal sections.

Neuropsychological test findings in subjects with leukoaraiosis.

Focal periventricular white-matter changes (leukoaraiosis) have been identified incidentally on brain imaging in normal healthy individuals and more commonly in the elderly and in hypertensive individuals. It has been suggested that leukoaraiosis represents the early stages of Binswanger's leukoencephalopathy, a dementing process thought to be related to hypertensive cerebrovascular disease. To test this hypothesis, extensive neuropsychological tests were administered to 50 consecutive normotensive, middle-aged, healthy volunteers. Ten subjects (20%) had white-matter changes on magnetic resonance scans; 40 subjects (80%) had normal scans. The differences observed on neuropsychological testing between subjects with and without leukoaraiosis were not significant. While this study argues against a link between leukoaraiosis and dementia, prospective longitudinal studies are needed to determine the value of leukoaraiosis in predicting future cognitive decline.

Neuro-Behcet disease: two cases and neuroradiologic findings.

In two cases of Behcet disease, neurologic disorders antedated the characteristic ocular or mucocutaneous lesions by 6 to 32 weeks. Neuroradiologic investigation demonstrated expanding avascular foci in the basal ganglia, probably representing areas of infarction secondary to vasculitis.

Correlation of magnetic resonance imaging with neuropsychological testing in multiple sclerosis.

Previous research has suggested that cerebral lesions observed on magnetic resonance imaging (MRI) of MS patients are clinically "silent." We examined the validity of this assertion by correlating neuropsychological test performance with MRI findings in 53 MS patients. We used a semiautomated quantitation system to measure three MRI variables: total lesion area (TLA), ventricular-brain ratio (VBR), and size of the corpus callosum (SCC). Stepwise multiple regression analyses indicated that TLA was a robust predictor of cognitive dysfunction, particularly for measures of recent memory, abstract/conceptual reasoning, language, and visuospatial problem solving. SCC predicted test performance on measures on mental processing speed and rapid problem solving, while VBR did not independently predict cognitive test findings. These findings suggest that cerebral lesions in MS produce cognitive dysfunction and that MRI may be a useful predictor of cognitive dysfunction.

Determination of language dominance using functional MRI: a comparison with the Wada test.

We performed functional MRI (FMRI) in 22 consecutive epilepsy patients undergoing intracarotid amobarbital (Wada) testing and compared language lateralization measures obtained with the two procedures. FMRI used a single-word semantic decision task previously shown to activate lateralized language areas in normal adults. Correlation between the two tests was highly significant (r = 0.96; 95% CIs 0.90 to 0.98; p < 0.0001). These results validate the FMRI technique and suggest that "active" areas observed with this semantic processing task correspond to those underlying hemispheric dominance for language. This strong correlation observed supports the view that language lateralization is a continuous rather than a dichotomous variable. In addition to lateralization information, FMRI consistently demonstrated focal regions of activity in lateral frontal and temporo-parieto-occipital cortex. These functional maps may be helpful in defining the boundaries of surgical excisions.

Cat optic nerve imaging with metrizamide.

Metrizamide is a water-soluble, nonionic radiocontrast medium that penetrates better into narrow subarachnoid spaces than do oily contrast media or gas. We performed metrizamide optic nerve thecography on five cats with iatrogenic orbital lesions. Optic thecograms successfully demonstrated displacement of the optic nerve, obstruction of the optic nerve sheath subarachnoid space, and extravasation of the contrast medium from a punctured optic nerve sheath. Metrizamide-induced seizures could be prevented by intramuscular preadministration of diazepam.

Intrathecal toxicity of iohexol vs. metrizamide. Survey and current state.

Arachnoiditis, a common finding in patients who have had previous myelograms or spinal surgery, can cause pain, paresis, and can slow elimination of contrast medium from the subarachnoid space. The role of contrast media in producing arachnoiditis has not been well defined but can be studied in a primate model. This study compared incidence of arachnoiditis in monkeys after myelograms using two nonionic contrast media, iohexol and metrizamide. Conditions were chosen to produce the greatest possible effect of contrast medium on the arachnoid. Animals were sacrificed 12 weeks after the myelogram and the dural sac was removed for examination by light microscope. Under adverse conditions, high doses and high concentrations of iohexol produced little arachnoiditis, while metrizamide produced mild to moderate arachnoiditis. Iohexol was shown to have a greater margin of safety then metrizamide, which is considered an important clinical advantage.