Richard Birgander

Venous and cerebrospinal fluid flow in multiple sclerosis: a case-control study.

The prevailing view on multiple sclerosis etiopathogenesis has been challenged by the suggested new entity chronic cerebrospinal venous insufficiency. To test this hypothesis, we studied 21 relapsing‐remitting multiple sclerosis cases and 20 healthy controls with phase‐contrast magnetic resonance imaging. In addition, in multiple sclerosis cases we performed contrast‐enhanced magnetic resonance angiography. We found no differences regarding internal jugular venous outflow, aqueductal cerebrospinal fluid flow, or the presence of internal jugular blood reflux. Three of 21 cases had internal jugular vein stenoses. In conclusion, we found no evidence confirming the suggested vascular multiple sclerosis hypothesis. ANN NEUROL 2010;68:255–259

Brain ventricular size in healthy elderly: comparison between evans index and volume measurement.

BACKGROUNDA precise definition of ventricular enlargement is important in the diagnosis of hydrocephalus as well as in assessing central atrophy. The Evans index (EI), a linear ratio between the maximal frontal horn width and the cranium diameter, has been extensively used as an indirect marker of ventricular volume (VV). With modern imaging techniques, brain volume can be directly measured. OBJECTIVETo determine reference values of intracranial volumes in healthy elderly individuals and to correlate volumes with the EI. METHODSMagnetic resonance imaging (3 T) was performed in 46 healthy white elderly subjects (mean age ± standard deviation, 71 ± 6 years) and in 20 patients (74 ± 7 years) with large ventricles according to visual inspection. VV, relative VV (RVV), and EI were assessed. Ventricular dilation was defined using VV and EI by a value above the 95th percentile range for healthy elderly individuals. RESULTSIn healthy elderly subjects, we found VV = 37 ± 18 mL, RVV = 2.47 ± 1.17%, and EI = 0.281 ± 0.027. Including the patients, there was a strong correlation between EI and VV (R = 0.94) as well as between EI and RVV (R = 0.95). However, because of a wide 95% prediction interval (VV: ±45 mL; RVV: ± 2.54%), EI did not give a sufficiently good estimate of VV and RVV. CONCLUSIONVV (or RVV) and the EI reflect different properties. The exclusive use of EI in clinical studies as a marker of enlarged ventricles should be questioned. We suggest that the definition of dilated ventricles in white elderly individuals be defined as VV >77 mL or RVV >4.96 %. Future studies should compare intracranial volumes with clinical characteristics and prognosis.

Idiopathic normal pressure hydrocephalus: increased supplementary motor activity accounts for improvement after CSF drainage.

In patients with idiopathic normal pressure hydrocephalus (INPH), the changes in brain function that take place in conjunction with improved behavioural performance after CSF drainage is still unknown. In this study, we use functional MRI (fMRI) to investigate the changes in cortical activity that accompany improved motor and cognitive performance after long-term external lumbar drainage (ELD) of CSF in patients with INPH. Eighteen INPH patients were initially included together with age- and sex-matched controls. Data from 11 INPH patients were analysed both before and after ELD. The average drain volume for these 11 patients was 400 ml/3 days. Brain activation was investigated by fMRI before and after the procedure on a 1.5T Philips scanner using protocols taxing motor performance (finger tapping and reaction time) and cognitive functioning (memory and attention). Behavioural data were compared using non-parametric tests at a significance level of 0.05, whereas fMRI data were analysed by statistical parametric mapping including conjunction analysis of areas with enhanced activity after drainage in patients and areas activated in controls (P < 0.005, uncorrected). Improved regions were defined as areas in the INPH brain that increased in activity after ELD with the requirement that the same areas were activated in control subjects. Following ELD, right-hand finger tapping improved from 104 +/- 38 to 117 +/- 25 (mean +/- SD) (P = 0.02). Left-hand finger tapping showed a tendency to improve, the number of keystrokes increasing from 91 +/- 40 to 105 +/- 20 (P = 0.12). Right-hand reaction time improved from 1630 +/- 566 ms to 1409 +/- 442 ms, whereas left-hand reaction time improved from 1760 +/- 600 ms to 1467 +/- 420 ms (both P-values = 0.01). Significant improvements in motor performance were accompanied by bilateral increased activation in the supplementary motor area. No improvement was found in cognitive functioning. The results suggest that motor function recovery in INPH patients after CSF removal is related to enhanced activity in medial parts of frontal motor areas considered crucial for motor planning; a finding consistent with INPH being a syndrome related to a reversible suppression of frontal periventricular cortico-basal ganglia-thalamo-cortical pathways.

Blood flow distribution in cerebral arteries

High-resolution phase—contrast magnetic resonance imaging can now assess flow in proximal and distal cerebral arteries. The aim of this study was to describe how total cerebral blood flow (tCBF) is distributed into the vascular tree with regard to age, sex and anatomic variations. Forty-nine healthy young (mean 25 years) and 45 elderly (mean 71 years) individuals were included. Blood flow rate (BFR) in 21 intra- and extracerebral arteries was measured. Total cerebral blood flow was defined as BFR in the internal carotid plus vertebral arteries and mean cerebral perfusion as tCBF/brain volume. Carotid/vertebral distribution was 72%/28% and was not related to age, sex, or brain volume. Total cerebral blood flow (717±123 mL/min) was distributed to each side as follows: middle cerebral artery (MCA), 21%; distal MCA, 6%; anterior cerebral artery (ACA), 12%, distal ACA, 4%; ophthalmic artery, 2%; posterior cerebral artery (PCA), 8%; and 20% to basilar artery. Deviating distributions were observed in subjects with ‘fetal’ PCA. Blood flow rate in cerebral arteries decreased with increasing age (P<0.05) but not in extracerebral arteries. Mean cerebral perfusion was higher in women (women: 61±8; men: 55±6 mL/min/100 mL, P<0.001). The study describes a new method to outline the flow profile of the cerebral vascular tree, including reference values, and should be used for grading the collateral flow system.

Phase contrast MRI quantification of pulsatile volumes of brain arteries, veins, and cerebrospinal fluids compartments: Repeatability and physiological interactions

To study measurement repeatability and physiological determinants on measurement stability for phase contrast MRI (PC‐MRI) measurements of cyclic volume changes (ΔV) of brain arteries, veins, and cerebrospinal fluid (CSF) compartments.

Reference values for CSF outflow resistance and intracranial pressure in healthy elderly

Objective: The intracranial pressure (ICP) and CSF outflow resistance (Rout) are essential to describe the dynamics of the CSF system. Rout affects ICP, pulse amplitudes, CSF absorption, and the compliance of the system. The objective of this study was to determine the reference values in healthy elderly subjects. Methods: Elderly people (60–82 years), who considered themselves healthy, were recruited through an advertisement in the local newspaper. All were evaluated with a 3-T MRI. Subjects were eligible if they did not have any psychiatric or neurologic disorder or signs of advanced atherosclerotic disease. CSF resting pressure (ICP) and Rout were determined by a constant pressure infusion method with the patient in the supine position. The study population consisted of 40 subjects (mean age 70 years; 23 women). Results: The median ICP was 11.6 mm Hg (15.8 cmH2O) and the reference interval was ICP 7.8–14.3 mm Hg (10.6–19.4 cmH2O) (defined as 5th to 95th percentiles). The median Rout was 8.6 mm Hg/mL/min. The variation in Rout was large and not normally distributed. The 90th percentile of Rout was 17.4 mm Hg/mL/min. Conclusions: This study reports reference values for ICP and Rout and should be used for comparison when investigating disorders with suspected CSF dynamic disturbances in the elderly. ICP was in the same range as that reported in the young and middle-aged. The upper limit of Rout was higher than previously believed to be the upper limit of normal for this age group.

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.

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.

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.

Assessment of craniospinal pressure-volume indices

BACKGROUND AND PURPOSE: The PVICC 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 PVICC 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 PVICC 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 PVICC 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 PVICC. This study produced normative values and showed that the major compensatory contribution was located intracranially.