Cerebrospinal fluid and blood flow patterns in idiopathic normal pressure hydrocephalus.

OBJECTIVES: Increased aqueduct cerebrospinal fluid (CSF) flow pulsatility and, recently, a reversed CSF flow in the aqueduct have been suggested as hallmarks of idiopathic normal pressure hydrocephalus (INPH). However, these findings have not been adequately confirmed. Our objective was to investigate the flow of blood and CSF in INPH, as compared to healthy elderly, in order to clarify which flow parameters are related to the INPH pathophysiology. MATERIALS AND METHODS: Sixteen INPH patients (73 years) and 35 healthy subjects (72 years) underwent phase-contrast magnetic resonance imaging (MRI). Measurements included aqueduct and cervical CSF flow, total arterial inflow (tCBF; i.e. carotid + vertebral arteries), and internal jugular vein flow. Flow pulsatility, net flow, and flow delays were compared (multiple linear regression, correcting for sex and age). RESULTS: Aqueduct stroke volume was higher in INPH than healthy (148±95 vs 90±50 mL, P<.05). Net aqueduct CSF flow was similar in magnitude and direction. The cervical CSF stroke volume was lower (P<.05). The internal carotid artery net flow was lower in INPH (P<.05), although tCBF was not. No differences were found in internal jugular vein flow or flow delays. CONCLUSIONS: The typical flow of blood and CSF in INPH was mainly characterized by increased CSF pulsatility in the aqueduct and reduced cervical CSF pulsatility. The direction of mean net aqueduct CSF flow was from the third to the fourth ventricle. Our findings may reflect the altered distribution of intracranial CSF volume in INPH, although the causality of these relationships is unclear.

Accuracy of Parenchymal Cerebral Blood Flow Measurements Using Pseudocontinuous Arterial Spin-Labeling in Healthy Volunteers.

BACKGROUND AND PURPOSE: The arterial spin-labeling method for CBF assessment is widely available, but its accuracy is not fully established. We investigated the accuracy of a whole-brain arterial spin-labeling technique for assessing the mean parenchymal CBF and the effect of aging in healthy volunteers. Phase-contrast MR imaging was used as the reference method. MATERIALS AND METHODS: Ninety-two healthy volunteers were included: 49 young (age range, 20-30 years) and 43 elderly (age range, 65-80 years). Arterial spin-labeling parenchymal CBF values were averaged over the whole brain to quantify the mean pCBF(ASL) value. Total CBF was assessed with phase-contrast MR imaging as the sum of flows in the internal carotid and vertebral arteries, and subsequent division by brain volume returned the pCBF(PCMRI) value. Accuracy was considered as good as that of the reference method if the systematic difference was less than 5 mL/min/100 g of brain tissue and if the 95% confidence intervals were equal to or better than ±10 mL/min/100 g. RESULTS: pCBF(ASL) correlated to pCBF(PCMRI) (r = 0.73; P < .001). Significant differences were observed between the pCBF(ASL) and pCBF(PCMRI) values in the young (P = .001) and the elderly (P < .001) volunteers. The systematic differences (mean ± 2 standard deviations) were -4 ± 14 mL/min/100 g in the young subjects and 6 ± 12 mL/min/100 g in the elderly subjects. Young subjects showed higher values than the elderly subjects for pCBF(PCMRI) (young, 57 ± 8 mL/min/100 g; elderly, 54 ± 7 mL/min/100 g; P = .05) and pCBF(ASL) (young, 61 ± 10 mL/min/100 g; elderly, 48 ± 10 mL/min/100 g; P < .001). CONCLUSIONS: The limits of agreement were too wide for the arterial spin-labeling method to be considered satisfactorily accurate, whereas the systematic overestimation in the young subjects and underestimation in the elderly subjects were close to acceptable. The age-related decrease in parenchymal CBF was augmented in arterial spin-labeling compared with phase-contrast MR imaging.

Age-dependency of ocular parameters: a cross sectional study of young and elderly healthy subjects.

PURPOSE: To investigate the effect of aging on ocular parameters, including intraocular pressure (IOP), measured with different tonometry methods in healthy young (HY) and healthy elderly (HE) subjects and to study the effect of corneal parameters on tonometry methods. METHODS: In this prospective, cross-sectional study, fifty eyes of 50 HY subjects (28 females, 22-31 years of age) and 43 eyes of 43 HE subjects (22 females, 64-79) were included. IOP was measured with four tonometry methods in a standardized order: ocular response analyser (ORA), dynamic contour tonometry (DCT), applanation resonance tonometry (ART) and Goldmann applanation tonometry (GAT). Other measurements included axial length (AL), central corneal thickness (CCT), corneal curvature (CC), anterior chamber volume (ACV), corneal hysteresis (CH) and corneal resistance factor (CRF). RESULTS: The mean IOP (HY/HE; mmHg ± standard deviation (SD)) was 12.2 ± 2.2/14.1 ± 3.5 with GAT. IOP was significantly higher (difference ± standard error) in HE compared to HY measured with an ORA (+3.1 mmHg ± 0.6), GAT (+1.9 ± 0.6) and DCT (+1.6 ± 0.6). No significant difference was found in IOP measured with ART. CH and ACV were significantly lower in HE compared to HY. There was no difference between the groups in CCT, CC, AL or CRF. No tonometry method was dependant on CCT or CC. CONCLUSIONS: IOP measured with an ORA and via DCT and GAT was higher in HE compared to HY Swedish subjects, while IOP measured with ART did not differ between the groups. In these homogeneous groups, tonometry methods were independent of CCT and CC.

Measuring pulsatile flow in cerebral arteries using 4D phase-contrast MR imaging.

BACKGROUND AND PURPOSE: 4D PCMRI can be used to quantify pulsatile hemodynamics in multiple cerebral arteries. The aim of this study was to compare 4D PCMRI and 2D PCMRI for assessments of pulsatile hemodynamics in major cerebral arteries. MATERIALS AND METHODS: We scanned the internal carotid artery, the anterior cerebral artery, the basilar artery, and the middle cerebral artery in 10 subjects with a single 4D and multiple 2D PCMRI acquisitions by use of a 3T system and a 32-channel head coil. We assessed the agreement regarding net flow and the volume of arterial pulsatility (ΔV) for all vessels. RESULTS: 2D and 4D PCMRI produced highly correlated results, with r = 0.86 and r = 0.95 for ΔV and net flow, respectively (n = 69 vessels). These values increased to r = 0.93 and r = 0.97, respectively, during investigation of a subset of measurements with <5% variation in heart rate between the 4D and 2D acquisition (n = 31 vessels). Significant differences were found for ICA and MCA net flow (P = .004 and P < .001, respectively) and MCA ΔV (P = .006). However, these differences were attenuated and no longer significant when the subset with stable heart rate (n = 31 vessels) was analyzed. CONCLUSIONS: 4D PCMRI provides a powerful methodology to measure pulsatility of the larger cerebral arteries from a single acquisition. A large part of differences between measurements was attributed to physiologic variations. The results were consistent with 2D PCMRI.

Automated determination of brain parenchymal fraction in multiple sclerosis.

BACKGROUND AND PURPOSE: Brain atrophy is a manifestation of tissue damage in MS. Reduction in brain parenchymal fraction is an accepted marker of brain atrophy. In this study, the approach of synthetic tissue mapping was applied, in which brain parenchymal fraction was automatically calculated based on absolute quantification of the tissue relaxation rates R1 and R2 and the proton attenuation. MATERIALS AND METHODS: The BPF values of 99 patients with MS and 35 control subjects were determined by using SyMap and tested in relationship to clinical variables. A subset of 5 patients with MS and 5 control subjects were also analyzed with a manual segmentation technique as a reference. Reproducibility of SyMap was assessed in a separate group of 6 healthy subjects, each scanned 6 consecutive times. RESULTS: Patients with MS had significantly lower BPF (0.852 ± 0.0041, mean ± SE) compared with control subjects (0.890 ± 0.0040). Significant linear relationships between BPF and age, disease duration, and Expanded Disability Status Scale scores were observed (P < .001). A strong correlation existed between SyMap and the reference method (r = 0.96; P < .001) with no significant difference in mean BPF. Coefficient of variation of repeated SyMap BPF measurements was 0.45%. Scan time was <6 minutes, and postprocessing time was <2 minutes. CONCLUSIONS: SyMap is a valid and reproducible method for determining BPF in MS within a clinically acceptable scan time and postprocessing time. Results are highly congruent with those described using other methods and show high agreement with the manual reference method.

Evaluation of automatic measurement of the intracranial volume based on quantitative MR imaging.

BACKGROUND AND PURPOSE: Brain size is commonly described in relation to ICV, whereby accurate assessment of this quantity is fundamental. Recently, an optimized MR sequence (QRAPMASTER) was developed for simultaneous quantification of T1, T2, and proton density. ICV can be measured automatically within minutes from QRAPMASTER outputs and a dedicated software, SyMRI. Automatic estimations of ICV were evaluated against the manual segmentation. MATERIALS AND METHODS: In 19 healthy subjects, manual segmentation of ICV was performed by 2 neuroradiologists (Obs1, Obs2) by using QBrain software and conventional T2-weighted images. The automatic segmentation from the QRAPMASTER output was performed by using SyMRI. Manual corrections of the automatic segmentation were performed (corrected-automatic) by Obs1 and Obs2, who were blinded from each other. Finally, the repeatability of the automatic method was evaluated in 6 additional healthy subjects, each having 6 repeated QRAPMASTER scans. The time required to measure ICV was recorded. RESULTS: No significant difference was found between reference and automatic (and corrected-automatic) ICV (P > .25). The mean difference between the reference and automatic measurement was -4.84 ± 19.57 mL (or 0.31 ± 1.35%). Mean differences between the reference and the corrected-automatic measurements were -0.47 ± 17.95 mL (-0.01 ± 1.24%) and -1.26 ± 17.68 mL (-0.06 ± 1.22%) for Obs1 and Obs2, respectively. The repeatability errors of the automatic and the corrected-automatic method were <1%. The automatic method required 1 minute 11 seconds (SD = 12 seconds) of processing. Adding manual corrections required another 1 minute 32 seconds (SD = 38 seconds). CONCLUSIONS: Automatic and corrected-automatic quantification of ICV showed good agreement with the reference method. SyMRI software provided a fast and reproducible measure of ICV.

Ventriculomegaly and balance disturbances in patients with TIA.

OBJECTIVES: Dilated ventricles and gait disturbances are common in the elderly, and these are also features of the treatable syndrome idiopathic normal pressure hydrocephalus (INPH). Many studies report an association between hypertension, vascular disease and INPH. The objective of this study was to study the frequency of ventriculomegaly, with or without hydrocephalic symptoms, in patients who had suffered from a transitory ischaemic attack (TIA). METHODS: Gait, Romberg sign, tandem standing and one-leg stance were consecutively evaluated in elderly > 24 h after a TIA. Ventricular size, white matter lesions and atrophy were assessed on computed tomography scans. Exclusion criteria were conditions possibly influencing the balance tests. RESULTS: eventy-six patients with TIA out of 105 were included. Ventriculomegaly [Evans Index (EI) > 0.30] was observed in 19.7% and very large ventricles (EI > 0.33) in 7.9%. Ventriculomegaly was found in 58% of the patients with a previous 'history of balance or gait disturbance', but only in 12% of those without any prior disturbance (chi-square test; P = 0.0009). Three out of 76 patients with TIA (3.9%) fulfilled both radiological and clinical criteria for 'possible INPH'. CONCLUSION: Ventriculomegaly is a common finding in elderly. One out of 20 patients with TIA may suffer from INPH, existing before and independent of the TIA diagnosis. Therefore, patients presenting with ventriculomegaly and gait/balance disturbances not attributable to other causes should be referred to a hydrocephalus centre or a neurologist with special interest in INPH.

MR imaging of brain volumes: evaluation of a fully automatic software.

BACKGROUND AND PURPOSE: Automatic assessment of brain volumes is needed in research and clinical practice. Manual tracing is still the criterion standard but is time-consuming. It is important to validate the automatic tools to avoid the problems of clinical studies drawing conclusions on the basis of brain volumes estimated with methodologic errors. The objective of this study was to evaluate a new commercially available fully automatic software for MR imaging of brain volume assessment. Automatic and expert manual brain volumes were compared. MATERIALS AND METHODS: MR imaging (3T, axial T2 and FLAIR) was performed in 41 healthy elderly volunteers (mean age, 70 ± 6 years) and 20 patients with hydrocephalus (mean age, 73 ± 7 years). The software Q(Brain) was used to manually and automatically measure the following brain volumes: ICV, BTV, VV, and WMHV. The manual method has been previously validated and was used as the reference. Agreement between the manual and automatic methods was evaluated by using linear regression and Bland-Altman plots. RESULTS: There were significant differences between the automatic and manual methods regarding all volumes. The mean differences were ICV = 49 ± 93 mL (mean ± 2SD, n = 61), BTV = 11 ± 70 mL, VV = -6 ± 10 mL, and WMHV = 2.4 ± 9 mL. The automatic calculations of brain volumes took approximately 2 minutes per investigation. CONCLUSIONS: The automatic tool is promising and provides rapid assessment of brain volumes. However, the software needs improvement before it is incorporated into research or daily use. Manual segmentation remains the reference method.

Assessment of craniospinal pressure-volume indices.

BACKGROUND AND PURPOSE: The PVI(CC) of the craniospinal compartment defines the shape of the pressure-volume curve and determines the damping of cyclic arterial pulsations. Despite no reports of direct measurements of the PVI(CC) among healthy elderly, it is believed that a change away from adequate accommodation of cardiac-related pulsations may be a pathophysiologic mechanism seen in neurodegenerative disorders such as Alzheimer disease and idiopathic normal pressure hydrocephalus. In this study, blood and CSF flow measurements are combined with lumbar CSF infusion measurements to assess the craniospinal PVI(CC) and its distribution of cranial and spinal compartments in healthy elderly. MATERIALS AND METHODS: Thirty-seven healthy elderly were included (60-82 years of age). The cyclic arterial volume change and the resulting shift of CSF to the spinal compartment were quantified by PC-MR imaging. In addition, each subject underwent a lumbar CSF infusion test in which the magnitude of cardiac-related pulsations in intracranial pressure was quantified. Finally, the PVI was calculated by using a mathematic model. RESULTS: After excluding 2 extreme values, the craniospinal PVI(CC) was calculated to a mean of 9.8 ± 2.7 mL and the estimated average 95% confidence interval of individual measurements was ± 9%. The average intracranial and spinal contributions to the overall compliance were 65% and 35% respectively (n = 35). CONCLUSIONS: Combining lumbar CSF infusion and PC-MR imaging proved feasible and robust for assessment of the craniospinal PVI(CC). This study produced normative values and showed that the major compensatory contribution was located intracranially.

Ventricular dilation as an instability of intracranial dynamics.

We address the question of the ventricles' dilation as a possible instability of the intracranial dynamics. The ventricular system is shown to be governed by a dynamical equation derived from first principles. This general nonlinear scheme is linearized around a well-defined steady state which is mapped onto a pressure-volume model with an algebraic effective compliance depending on the ventricles' geometry, the ependyma's elasticity, and the cerebrospinal fluid (CSF) surface tension. Instabilities of different natures are then evidenced. A first type of structural instability results from the compelling effects of the CSF surface tension and the elastic properties of the ependyma. A second type of dynamical instability occurs for low enough values of the aqueduct's conductance. This last case is then shown to be accompanied by a spontaneous ventricle's dilation. A strong correlation with some active hydrocephalus is evidenced and discussed. The transfer function of the ventricles, compared to a low-pass filter, are calculated in both the stable and unstable regimes and appear to be very different.