Noam Alperin

Hydrodynamic Modeling of Cerebrospinal Fluid Motion Within the Spinal Cavity

The fluid that resides within cranial and spinal cavities, cerebrospinal fluid (CSF), moves in a pulsatile fashion to and from the cranial cavity. This motion can be measured hy magnetic resonance imaging (MRI) and may he of clinical importance in the diagnosis of several brain and spinal cord disorders such as hydrocephalus, Chiari malformation, and syringomyelia. In the present work, a geometric and hydrodynamic characterization of an anatomically relevant spinal canal model is presented. We found that inertial effects dominate the flow field under normal physiological flow rates. Along the length of the spinal canal, hydraulic diameter was found to vary significantly from 5 to 15 mm. The instantaneous Reynolds number at peak flow rate ranged from 150 to 450, and the Womersle number ranged from 5 to 17. Pulsatile flow calculations are presented for an idealized geometric representation of the spinal cavity. A linearized Navier-Stokes model of the pulsatile CSF flow was constructed based on MRI flow rate measurements taken on a healthy volunteer. The numerical model was employed to investigate effects of cross-sectional geometry and spinal cord motion on unsteady velocity, shear stress, and pressure gradientfields. The velocity field was shown to be blunt, due to the inertial character of the flow, with velocity peaks located near the boundaries of the spinal canal rather than at the midpoint between boundaries. The pressure gradient waveform was found to be almost exclusively dependent on the flow waveform and cross-sectional area. Characterization of the CSF dynamics in normal and diseased states may be important in understanding the pathophysiology of CSF related disorders. Flow models coupled with MRI flow measurements mnay become a noninvasive tool to explain the abnormal dynamics of CSF in related brain disorders as well as to determine concentration and local distribution of drugs delivered into the CSF space.

Quantifying the Effect of Posture on Intracranial Physiology in Humans by MRI Flow Studies

To quantify the effect of posture on intracranial physiology in humans by MRI, and demonstrate the relationship between intracranial compliance (ICC) and pressure (ICP), and the pulsatility of blood and CSF flows.

Improved phase-contrast flow quantification by three-dimensional vessel localization

In this paper, a method of three-dimensional (3D) vessel localization is presented to allow the identification of a vessel of interest, the selection of a vessel segment, and the determination of a slice orientation to improve the accuracy of phase-contrast magnetic resonance (PCMR) angiography. A marching-cube surface-rendering algorithm was used to reconstruct the 3D vasculature. Surface-rendering was obtained using an iso-surface value determined from a maximum intensity projection (MIP) image. This 3D vasculature was used to find a vessel of interest, select a vessel segment, and to determine the slice orientation perpendicular to the vessel axis. Volumetric flow rate (VFR) was obtained in a phantom model and in vivo using 3D localization with double oblique cine PCMR scanning. PCMR flow measurements in the phantom showed 5. 2% maximum error and a standard deviation of 9 mL/min during steady flow, 7.9% maximum error and a standard deviation of 13 mL/min during pulsatile flow compared with measurements using an ultrasonic transit-time flowmeter. PCMR VFR measurement error increased with misalignment at 10, 20, and 30 degrees oblique to the perpendicular slice in vitro and in vivo. The 3D localization technique allowed precise localization of the vessel of interest and optimal placement of the slice orientation for minimum error in flow measurements.

Blood-flow models of the circle of Willis from magnetic resonance data

Detailed knowledge of the cerebral hemodynamics is important for a variety of clinical applications. Cerebral perfusion depends not only on the status of the diseased vessels but also on the patency of collateral pathways provided by the circle of Willis. Due to the large anatomical and physiologic variability among individuals, realistic patient-specific models can provide new insights into the cerebral hemodynamics. This paper presents an image-based methodology for constructing patient-specific models of the cerebral circulation. This methodology combines anatomical and physiologic imaging techniques with computer simulation technology. The methodology is illustrated with a finite element model constructed from magnetic resonance image data of a normal volunteer. Several of the remaining challenging problems are identified. This work represents a starting point in the development of realistic models that can be applied to the study of cerebrovascular diseases and their treatment.

PUBS: pulsatility-based segmentation of lumens conducting non-steady flow.

Dynamic velocity‐encoded phase‐contrast MRI (PC‐MRI) techniques are being used increasingly to quantify pulsatile flows for a variety of clinical applications. Studies suggest that the reliability of flow quantitation with PC‐MRI appears to be dominated by the consistency in the delineation of the lumen boundary. An automated method that utilizes both spatial and temporal information has been developed for improved accuracy and reproducibility. The methods accuracy was evaluated using a flow phantom with 8‐ and 5‐mm‐diameter lumens at two different flow rates. The reproducibility of the method was further evaluated with arterial, venous, and cerebrospinal fluid flow data from human subjects. The results were compared with measurements obtained manually by observers of different skill levels. Measurement values obtained manually were consistently smaller than those obtained with the pulsatility‐based segmentation (PUBS) method. For the 8‐mm lumen, significant improvements in measurement accuracy were obtained. Average lumen area measurement errors of about 18% for the high and low flows, obtained manually by a skilled observer, were reduced to 2.9% and 4.8%, respectively. For the 5‐mm lumen, the skilled observer underestimated the lumen area by 13%, while the PUBS method overestimated the lumen area by 28%. Overestimated lumen area measurements for the smaller lumen are attributed to the partial‐volume effect. There was significantly less measurement variability with the PUBS method. An average fourfold reduction in interobserver measurement variability was obtained with the new method. Magn Reson Med 49:934–944, 2003.

MRI study of cerebral blood flow and CSF flow dynamics in an upright posture: the effect of posture on the intracranial compliance and pressure

Postural related changes in cerebral hemodynamics and hydrodynamics were studied using Magnetic Resonance Imaging (MRI) measurements of cerebral blood flow and cerebrospinal fluid (CSF) flow dynamics. Ten healthy volunteers (mean age 29 +/- 7) were studied in supine and upright (sitting) postures. A Cine phase-contrast MRI technique was used to image the pulsatile blood flow to the brain, the venous outflow through the internal jugular, epidural, and vertebral veins, and the bi-directional CSF flow between the cranium and the spinal canal. Previously published analyses were applied to calculate and compare total cerebral blood flow (TCBF), intracranial compliance and pressure in both postures. A lower (12%) mean TCBF was measured in the upright position compared to supine position. A considerable smaller amount of CSF flow between the cranium and the spinal canal (58%), a much larger intracranial compliance (a 2.8-fold increase), and a corresponding decrease in the MRI-derived ICP were also measured in the sitting position. These changes suggest that the increased cerebrovascular and intracranial compliances in the upright posture are primarily due to reduced amounts of blood and CSF residing in their respective intracranial compartments in the upright position. This work demonstrates the ability to quantify neurophysiologic parameters associated with regulation of cerebral hemodynamics and hydrodynamics from dynamic MR imaging of blood and CSF flows.

Chronic ischemic stroke model in cynomolgus monkeys: behavioral, neuroimaging and anatomical study.

Abstract Previous nonhuman primate stroke models have employed temporary occlusion of arteries, had limited behavioral testing and imaging, and focused on the short-term outcome. Our goals were 1. to develop a stable model of chronic stroke in the nonhuman primate, 2. to study in vivo the long-term biochemical changes in the area adjacent to the infarct, using proton magnetic resonance spectroscopy (1H MRS), and 3. evaluate these changes in relation to the histopathological effects of stroke. Four adult cynomologous monkeys had an occlusion of the M1 segment of the right MCA. Behavioral tests included a clinical rating scale, motor planning task, fine motor task, and activity monitoring. Eight months afterwards, MRI and 1H MRS were performed. Following the imaging studies the monkeys were perfused transcardially, their brains extracted and processed. Nissl staining and immunohistochemistry for neuronal markers (NeuN) were performed and used to measure the lesion volume and neuronal optical density (OD). All animals developed a left hemiparesis and were unable to perform a fine motor task with the left hand. There was a significant (31%) decline in the motor planning ability with the nonparetic extremity. Monkeys displayed a stooped posture, episodes of rotation to the side of the lesion, partial left hemianopsia, and transient changes in activity. The clinical signs improved over the first 6–8 weeks but the deficits remained stable for the remaining six months of follow up. MRI demonstrated a subcortical and cortical infarction in the right MCA distribution. 1H MRS data detected a significant decrease in the N-acetyl-aspartate (NAA)/creatine (Cr) ratio in the area adjacent to the infarction (VOI-St) compared to a mirror area in the contralateral hemisphere (VOI-Co). Histopathological measurements revealed a significant decline in neuronal crosssectional area and neuronal optical density in the region of the VOI-St. We established a stable and reproducible model of chronic stroke in the MCA distribution, in the macaque monkey. Our data indicate that NAA detected by 1H MRS can be used to measure neuronal loss in vivo and help target this area for intervention. Our model may be particularly suitable for studies testing the effects of therapeutic strategies involving neural or stem cell transplantation, trophic factors or gene therapy.

Magnetic resonance imaging of the levator veli palatini muscle in speakers with repaired cleft palate.

Objective: To obtain detailed anatomic and physiologic information on the levator veli palatini muscle from MRI in individuals with repaired cleft palate and to compare the results with those from normal subjects reported by Ettema et al. (2002). Design: Prospective study. Setting: University-based hospital. Participants: Four men (ages 22 to 43 years) with repaired cleft lip and palate. Main Outcome Measures: Four quantitative measurements of the levator veli palatini muscle from rest position and dynamic speech magnetic resonance images were obtained: the distance between the origins of the muscle, angle of origin of the muscle, muscle length, and muscle thickness. Results: The length and thickness of the levator veli palatini muscle varied among the subjects and were different from measurements obtained from normal subjects in a previous study. The distance between origin points, length, and thickness of the levator veli palatini muscle were smaller than those of the normal subjects. There were systematic changes of the levator veli palatini muscle, depending upon vowel and consonant types. Levator veli palatini muscle angle of origin and length became progressively smaller from rest, nasal consonants, low vowels, high vowels, and fricative consonants. These changes are consistent with those of the normal subjects. Conclusions: This study contributes to a better understanding of cleft palate anatomy in comparison with normal anatomy of the levator veli palatini muscle. The use of MRI shows promise as an important tool in the diagnosis and eventual aid to treatment decisions for individuals born with cleft palate.

Evidence for the importance of extracranial venous flow in patients with idiopathic intracranial hypertension (IIH)

Idiopathic intracranial hypertension (IIH) is characterized by increased ICP without evidence for intracranial mass lesion. Although the pathogenesis remains unknown, some association was found with intracranial venous thrombosis. To our knowledge, the extracranial venous drainage was not systematically evaluated in these patients. This study compared extracranial cerebral venous outflow in eight IIH patients and eight control subjects using magnetic resonance (MR) Venography and flow measurements. In addition, the study identified extracranial factors that affect cerebral venous drainage. In six of the IIH patients, either complete or partial functional obstruction of the internal jugular veins (IJVs) coupled with increased venous outflow through secondary venous channels was documented. On average, a four-fold increase in mean venous flow rate through the epidural and/or vertebral veins was measured in IIH patients compared with the healthy subjects. In one of the healthy subjects, intracranial venous outflow was studied also during external compression of the IJVs. Over 40% of the venous outflow through the IJVs shifted to the epidural veins and intracranial pressure, measured noninvasively by MRI, increased from 7.5 to 13 mmHg. Findings from this study suggest that increased ICP in some IIH patients could be associated with increased extracranial resistance to cerebral venous outflow.

Evaluating the effect of decompression surgery on cerebrospinal fluid flow and intracranial compliance in patients with chiari malformation with magnetic resonance imaging flow studies.

OBJECTIVE:To quantify the effect of decompression surgery on craniocervical junction hydrodynamics and on global intracranial compliance (ICC) in patients with Chiari I malformation by use of magnetic resonance measurements of cerebrospinal fluid and blood flow. Studying the effect of decompression surgery may improve our understanding of the pathophysiological characteristics of Chiari I malformation and aid in identifying patients who will benefit from the procedure. METHODS:Twelve patients were studied with a 1.5-T magnetic resonance imaging scanner before and after decompression surgery. Cine phase contrast magnetic resonance images were used to quantify maximum cord displacement, maximum systolic cerebrospinal fluid velocity and volumetric flow rate, and overall ICC. ICC was derived by use of a previously reported method that measures small changes in intracranial volume and pressure that occur naturally with each cardiac cycle. RESULTS:After surgery, changes were documented both in the local hydrodynamic parameters and in ICC. However, only the change in ICC, an average increase of more than 60%, was statistically significant. Increased ICC, which was associated with improved outcome, was measured in 10 of the 12 patients, no significant change was documented in 1 patient, and decreased ICC was measured in 1 patient whose symptoms persisted after surgery. CONCLUSION:An increase in the overall compliance of the intracranial compartment is the most significant and consistent change measured after decompression surgery. Changes in cord displacement, cerebrospinal fluid velocities, and flow in the craniospinal junction were less consistent and less affected by the operation. Thus, ICC may play an important role in the outcome of decompression surgery related to improving symptoms and restoring normal neurological hydrodynamics in patients with Chiari I malformations.