Sang H. Lee

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.

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.

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.

From Cerebrospinal Fluid Pulsation to Noninvasive Intracranial Compliance and Pressure Measured by MRI Flow Studies

The pulsation of the cerebrospinal fluid (CSF) has fascinated investigators of the intracranial physiology since it was first documented by invasive CSF pressure measurements. Advances in dynamic Magnetic Resonance Imaging (MRI) now enable visualization of and quantitation the CSF flow dynamics and has contributed to our understanding of the origin of CSF pulsation and its relation to the pulsatile blood flow. This, in turn, has led to the development of a noninvasive method for measurement of intracranial compliance and pressure by MRI. This article reviews the neurophysiologic and hydrodynamic principles that are the basis of the method, it describes the implementation of the method and validation studies to date with a non-human primate animal model, computer simulations, healthy human subjects and patients. The article further reviews the application of this method to study the effect of body posture on the cerebral physiology in humans through the relationships between blood and CSF flow dynamics. Finally, recent results from the application of the method in Chiari Malformations (CM) are briefly presented as an example of a potential clinical application of this methodology. The application to CM provided, for the first time, evidence of the important role intracranial compliance plays in the pathophysiology of this poorly understood disorder. The potential diagnostic value of an MRI-based measurement of ICP for other neurological problems is discussed.

Low-dose acetazolamide reverses periventricular white matter hyperintensities in iNPH.

Objective: To assess the effects of low-dose acetazolamide treatment on volumetric MRI markers and clinical outcome in idiopathic normal-pressure hydrocephalus (iNPH). Methods: We analyzed MRI and gait measures from 8 patients with iNPH with serial MRIs from an institutional review board–approved imaging protocol who had been treated off-label with low-dose acetazolamide (125–375 mg/day). MRI studies included fluid-attenuated inversion recovery and 3D T1-weighted high-resolution imaging. Automated analyses were employed to quantify each patients ventricular, global white matter hyperintensities (WMH), and periventricular WMH (PVH) volumes prior to and throughout treatment. Clinical outcome was based on gait changes assessed quantitatively using the Boon scale. Results: Five of 8 patients responded positively to treatment, with median gait improvement of 4 points on the Boon scale. A significant decrease in PVH volume (−6.1 ± 1.9 mL, p = 0.002) was seen in these patients following treatment. One patients gait was unchanged and 2 patients demonstrated worsened gait and were referred for shunt surgery. No reduction in PVH volume was detected in the latter 2 patients. Nonperiventricular WMH and lateral ventricle volumes remained largely unchanged in all patients. Conclusions: These preliminary findings provide new evidence that low-dose acetazolamide can reduce PVH and may improve gait in iNPH. PVH volume, reflecting transependymal CSF, is shown to be a potential MRI indicator of pharmacologic intervention effectiveness. Further studies of pharmacologic treatment of iNPH are needed and may be enhanced by incorporating quantitative MRI outcomes. Classification of evidence: This study provides Class IV evidence that low-dose acetazolamide reverses PVH volume and, in some cases, improves gait in iNPH.

Normobaric hypoxia and symptoms of acute mountain sickness: Elevated brain volume and intracranial hypertension

The study was undertaken to determine whether normobaric hypoxia causes elevated brain volume and intracranial pressure in individuals with symptoms consistent with acute mountain sickness (AMS).

Relationship between ventricular morphology and aqueductal cerebrospinal fluid flow in healthy and communicating hydrocephalus

Objectives:Differences in the magnitude of cerebrospinal fluid (CSF) volumetric flow through the cerebral aqueduct between healthy and hydrocephalic patients have been previously reported. However it is not clear whether this is directly related to the pathophysiology or secondary to altered ventricular morphology and hydrodynamics. This work aims to determine the role of anatomic and hydrodynamic factors in modulating the magnitude of CSF flow through the aqueduct. Materials and Methods:Twenty subjects (10 healthy and 10 patients with communicating hydrocephalus of different causes) were studied by MRI. Scans included T1-weighted 3D anatomic imaging and velocity-encoded cine phase-contrast scans of transcranial blood and CSF flows as well as CSF flow through the aqueduct. Anatomic MR data were used for quantitation of ventricular volumes, third ventricular width, and gray and white brain tissue volumes. Velocity-encoded imaging was used for quantitation of aqueductal and cervical CSF stroke volumes (SV), aqueductal lumen area, and systolic maximal intracranial volume change. Because data from normal and hydrocephalic patients were aggregated, a battery of statistical methods that accounted for the group effects were used. Partial correlation was used to determine which of these parameters were most significantly associated with aqueductal stroke volume (ASV). Multiple linear regression analyses were employed to identify anatomic and hydrodynamic models with the least amount of variables that are significant predictors of ASV. Finally, the association between the magnitude of ASV and the aqueductal lumen area, and its implication on the CSF flow dynamic characteristics and aqueductal pressure difference was established. Results:Using partial correlations, 5 of the 6 anatomic parameters and none of the hydrodynamic parameters and brain tissue volume were found to be statistically significant. The highest partial correlations were with the total ventricular volume (r = 0.838) and third ventricle width (r = 0.811). These parameters were also found to be significant predictors of ASV in the multiple linear regression analyses with third ventricle volume and group effects as insignificant predictors (F = 28.08, P < 0.0001, R2 = 0.85). On the other hand, both cervical CSF SV and maximal ICVC were found to be weak predictors of ASV with group effects as the only significant variable of the hydrodynamic model (F = 4.18, P = 0.023, R2 = 0.33). A combined anatomic–hydrodynamic model including the predictive variables of the anatomic model and the ICVC provides the strongest coefficient of determination (R2 = 0.873). Pearson correlation analysis revealed a very strong relationship between ASV and the aqueductal lumen area (r = 0.947). Conclusions:Aqueductal CSF flow is strongly correlated with ventricular morphology, especially with the total ventricular volume and the third ventricle width, but not with the tested hydrodynamic parameters. In addition, ASV is linearly correlated with aqueductal lumen area, suggesting that the aqueductal CSF flow characteristics can be explained by oscillating pressure differences on the order of less than 0.01 mmHg. These findings may explain why a standalone ASV is a poor diagnostic marker and an insensitive indicator of shunt outcome in idiopathic normal pressure hydrocephalus.

EARLY EXPERIENCE FROM THE APPLICATION OF A NONINVASIVE MAGNETIC RESONANCE IMAGING-BASED MEASUREMENT OF INTRACRANIAL PRESSURE IN HYDROCEPHALUS

OBJECTIVE The decision for surgical intervention in hydrocephalic patients presenting with symptoms suggesting raised intracranial pressure (ICP) is challenging because radiographic ventricular size often lacks the specificity to predict abnormal ICP. An early assessment of the potential clinical usefulness of a noninvasive magnetic resonance imaging-based measurement of ICP (MR-ICP) in symptomatic hydrocephalic patients is reported. METHODS Twenty-seven symptomatic hydrocephalic patients (18 with shunts and 9 without shunts) underwent brain magnetic resonance imaging-based studies that included measurements of cerebrospinal fluid and blood flows to and from the cranial vault, from which measurements of ICP were derived using a previously described algorithm. The predictive values of the MR-ICP measurement were determined on the basis of whether or not the patient underwent a surgical treatment of a shunt placement or shunt revision within a 3-month period after the magnetic resonance imaging-based study. RESULTS MR-ICP values in these patients spanned a much wider range than in healthy control subjects. However, the majority of the patients (20 out of 26 patients) had MR-ICP values within the normal range. The short-term follow-up of patients who had normal MR-ICP measurement reveals that only one of the 20 patients required surgery. Consequently, the MR-ICP measurement has a strong negative predictive value (95% for all patients and 100% for patients without a shunt). CONCLUSION A finding of a normal MR-ICP value in hydrocephalic patients presenting with symptoms suggestive of abnormal ICP is a strong predictor for resolution of symptoms or stable outcome without surgical intervention.

MRI measurements of intracranial pressure in the upright posture: The effect of the hydrostatic pressure gradient

To add the hydrostatic component of the cerebrospinal fluid (CSF) pressure to magnetic resonance imaging (MRI)‐derived intracranial pressure (ICP) measurements in the upright posture for derivation of pressure value in a central cranial location often used in invasive ICP measurements.