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Purpose: Compare extracranial internal carotid artery flow rates and intracranial collateral use between conventional ≥ 50% carotid stenosis and carotid near-occlusion, and between symptomatic and asymptomatic carotid near-occlusion. Methods: We included patients with ≥ 50% carotid stenosis. Degree of stenosis was diagnosed on CTA. Mean blood flow rates were assessed with four-dimensional phase-contrast MRI. Results: We included 110 patients of which 83% were symptomatic, and 38% had near-occlusion. Near-occlusions had lower mean internal carotid artery flow (70 ml/min) than conventional ≥ 50% stenoses (203 ml/min, P <.001). Definite use of ≥ 1 collateral was found in 83% (35/42) of near-occlusions and 10% (7/68) of conventional stenoses (P <.001). However, there were no differences in total cerebral blood flow (514 ml/min vs. 519 ml/min, P =.78) or ipsilateral hemispheric blood flow (234 vs. 227 ml/min, P =.52), between near-occlusions and conventional ≥ 50% stenoses, based on phase-contrast MRI flow rates. There were no differences in total cerebral or hemispheric blood flow, or collateral use, between symptomatic and asymptomatic near-occlusions. Conclusion: Near-occlusions have lower internal carotid artery flow rates and more collateral use, but similar total cerebral blood flow and hemispheric blood flow, compared to conventional ≥ 50% carotid stenosis.

Background: Adequate cerebral perfusion is central during general anesthesia. However, perfusion is not readily measured bedside. Clinicians currently rely mainly on MAP as a surrogate even though the relationship between blood pressure and cerebral blood flow is not well understood. The aim of this study was to apply phase contrast MRI to characterize blood flow responses in healthy volunteers to commonly used pharmacological agents that increase or decrease arterial blood pressure. Methods: Eighteen healthy volunteers aged 30-50 years were investigated with phase contrast MRI. Intraarterial blood pressure monitoring was used. First, intravenous noradrenaline was administered to a target MAP of 20% above baseline. After a wash-out period, intravenous labetalol was given to a target MAP of 15% below baseline. Cerebral blood flow was measured using phase contrast MRI and defined as the sum of flow in the internal carotid arteries and vertebral arteries. CO was defined as the flow in the ascending aorta. Baseline median cerebral blood flow was 772 ml/min (interquartile range, 674 to 871), and CO was 5,874 ml/min (5,199 to 6,355). The median dose of noradrenaline was 0.17 µg · kg−1 · h−1 (0.14 to 0.22). During noradrenaline infusion, cerebral blood flow decreased to 705 ml/min (606 to 748; P = 0.001), and CO decreased to 4,995 ml/min (4,705 to 5,635; P = 0.01). A median dose of labetalol was 120 mg (118 to 150). After labetalol boluses, cerebral blood flow was unchanged at 769 ml/min (734 to 900; P = 0.68). CO increased to 6,413 ml/min (6,056 to 7,464; P = 0.03). Conclusion: In healthy awake subjects, increasing MAP using intravenous noradrenaline decreased cerebral blood flow and CO. This data does not support inducing hypertension with noradrenaline to increase cerebral blood flow. Cerebral blood flow was unchanged when decreasing MAP using labetalol.

Background: Compromised cerebral blood flow can contribute to future ischemic events in patients with symptomatic carotid artery disease. However, there is limited knowledge of the effects on cerebral hemodynamics resulting from a reduced internal carotid artery (ICA) blood flow rate (BFR). Purpose: Investigate how reduced ICA-BFR, relates to BFR in the cerebral arteries. Study Type: Prospective. Subjects: Thirty-eight patients, age 72 ± 6 years (11 female). Field Strength/Sequence: 3-Tesla, four-dimensional phase-contrast magnetic resonance imaging (4D-PCMRI). Assessment: Patients with ischemic stroke or transient ischemic attack were evaluated regarding the degree of stenosis. 4D-PCMRI was used to measure cerebral BFR in 38 patients with symptomatic carotid stenosis (≥50%). BFR in the cerebral arteries was assessed in two subgroups based on symptomatic ICA-BFR: reduced ICA-flow (<160 mL/minutes) and preserved ICA-flow (≥160 mL/minutes). BFR laterality was defined as a difference in the paired ipsilateral-contralateral arteries. Statistical Tests: Patients were grouped based on ICA-BFR (reduced vs. preserved). Statistical tests (independent sample t-test/paired t-test) were used to compare groups and hemispheres. Significance was determined at P < 0.05. Results: The degree of stenosis was not significantly different, 80% (95% confidence interval [CI] = 73%–87%) in the reduced ICA-flow vs. 72% (CI = 66%–76%) in the preserved ICA-flow; P = 0.09. In the reduced ICA-flow group, a significantly reduced BFR was found in the ipsilateral middle cerebral artery and anterior cerebral artery (A1), while significantly increased in the contralateral A1. Retrograde BFR was found in the posterior communicating artery and ophthalmic artery. Significant BFR laterality was present in all paired arteries in the reduced ICA-flow group, contrasting the preserved ICA-flow group (P = 0.14–0.93). Data Conclusions: 4D-PCMRI revealed compromised cerebral BFR due to carotid stenosis, n

BACKGROUND: Multiple prospective nonrandomized studies have shown 60% to 70% of patients with idiopathic normal pressure hydrocephalus (iNPH) improve with shunt surgery, but multicenter placebo-controlled trial data are necessary to determine its effectiveness. OBJECTIVE: To evaluate the effectiveness of cerebrospinal fluid shunting in iNPH through comparison of open vs placebo shunting groups at 4 months using a pilot study. METHODS: Patients were randomized to a Codman Certas Plus valve (Integra LifeSciences) set at 4 (open shunt group) or 8 (“virtual off”; placebo group). Patients and assessors were blinded to treatment group. The primary outcome measure was 10-m gait velocity. Secondary outcome measures included functional scales for bladder control, activities of daily living, depression, and quality of life. Immediately after 4-month evaluation, all shunts were adjusted in a blinded fashion to an active setting and followed to 12 months after shunting. RESULTS: A total of 18 patients were randomized. At the 4-month evaluation, gait velocity increased by 0.28 ± 0.28 m/s in the open shunt group vs 0.04 ± 0.17 m/s in the placebo group. The estimated treatment difference was 0.22 m/s ([P = .071], 95% CI −0.02 to 0.46). Overactive Bladder Short Form symptom bother questionnaire significantly improved in open shunt vs placebo (P = .007). The 4-month treatment delay did not reduce the subsequent response to active shunting, nor did it increase the adverse advents rate at 12 months. CONCLUSION: This multicenter, randomized pilot study demonstrates the effectiveness, safety, and feasibility of a placebo-controlled trial in iNPH, and found a trend suggesting gait velocity improves more in the open shunt group than in the placebo group.

Objective: High cerebral arterial pulsatility index (PI), white matter lesions (WMLs), enlarged perivascular spaces (PVSs), and lacunar infarcts are common findings in the elderly population, and considered indicators of small vessel disease (SVD). Here, we investigate the potential temporal ordering among these variables, with emphasis on determining whether high PI is an early or delayed manifestation of SVD. Methods: In a population-based cohort, 4D flow MRI data for cerebral arterial pulsatility was collected for 159 participants at baseline (age 64–68), and for 122 participants at follow-up 5 years later. Structural MRI was used for WML and PVS segmentation, and lacune identification. Linear mixed-effects (LME) models were used to model longitudinal changes testing for pairwise associations, and latent change score (LCS) models to model multiple relationships among variables simultaneously. Results: Longitudinal 5-year increases were found for WML, PVS, and PI. Cerebral arterial PI at baseline did not predict changes in WML or PVS volume. However, WML and PVS volume at baseline predicted 5-year increases in PI. This was shown for PI increases in relation to baseline WML and PVS volumes using LME models (R (Formula presented.) 0.24; p < 0.02 and R (Formula presented.) 0.23; p < 0.03, respectively) and LCS models ((Formula presented.) = 0.28; p = 0.015 and (Formula presented.) = 0.28; p = 0.009, respectively). Lacunes at baseline were unrelated to PI. Interpretation: In healthy older adults, indicators of SVD are related in a lead–lag fashion, in which the expression of WML and PVS precedes increases in cerebral arterial PI. Hence, we propose that elevated PI is a relatively late manifestation, rather than a risk factor, for cerebral SVD.

An internal carotid artery (ICA) stenosis can potentially decrease the perfusion pressure to the brain. In this study, computational fluid dynamics (CFD) was used to study if there was a hemispheric pressure laterality between the contra- and ipsilateral middle cerebral artery (MCA) in patients with a symptomatic ICA stenosis. We further investigated if this MCA pressure laterality (ΔPMCA) was related to the hemispheric flow laterality (ΔQ) in the anterior circulation, i.e., ICA, proximal MCA and the proximal anterior cerebral artery (ACA). Twenty-eight patients (73±6 years, range 59–80 years, 21 men) with symptomatic ICA stenosis were included. Flow rates were measured using 4D flow MRI data (PC-VIPR) and vessel geometries were obtained from computed tomography angiography. The ΔPMCA was calculated from CFD, where patient-specific flow rates were applied at all input- and output boundaries. The ΔPMCA between the contra- and ipsilateral side was 6.4±8.3 mmHg (p<0.001) (median 3.9 mmHg, range -1.3 to 31.9 mmHg). There was a linear correlation between the ΔPMCA and ΔQICA (r = 0.85, p<0.001) and ΔQACA (r = 0.71, p<0.001), respectively. The correlation to ΔQMCA was weaker (r = 0.47, p = 0.011). In conclusion, the MCA pressure laterality obtained with CFD, is a promising physiological biomarker that can grade the hemodynamic disturbance in patients with a symptomatic ICA stenosis.

PURPOSE: The spaceflight-associated neuro-ocular syndrome (SANS) affects astronauts on missions to the International Space Station (ISS). The SANS has blurred vision and ocular changes as typical features. The objective of this study was to investigate if microgravity can create deformations or movements of the eye or optic nerve, and if such changes could be linked to SANS. DESIGN: Cohort study. PARTICIPANTS: Twenty-two astronauts (age 48 ± 4 years). METHODS: The intervention consisted of time in microgravity at the ISS. We co-registered pre- and postspaceflight magnetic resonance imaging (MRI) scans and generated centerline representations of the optic nerve. The coordinates for the optic nerve head (ONH) and optic chiasm (OC) ends of the optic nerve were recorded along with the entire centerline path. MAIN OUTCOME MEASURES: Optic nerve length, ONH movement, and OC movement after time in microgravity. RESULTS: Optic nerve length increased (0.80 ± 0.74 mm, P < 0.001), primarily reflecting forward ONH displacement (0.63 ± 0.53 mm, P < 0.001). The forward displacement was positively related to mission duration, preflight body weight, and clinical manifestations of SANS. We also detected upward displacement of the OC (0.39 ± 0.50 mm, P = 0.002), indicative of brain movement, but this observation could not be linked to SANS. CONCLUSIONS: The spaceflight-induced optic nerve lengthening and anterior movement of the ONH support that SANS is caused by an altered pressure difference between the brain and the eye, leading to a forward push on the posterior of the eye. Body weight is a potential contributing risk factor. Direct assessment of intracranial pressure in space is required to verify the implicated mechanism behind the ocular findings in SANS., Reply: Peter Wostyn, Charles Robert Gibson, Thomas H. Mader, Re: Wåhlin et al.: Optic nerve length before and after spaceflight (Ophthalmology. 2021;128:309–316), Ophthalmology, Volume 128, Issue 5,2021, Pages e27-e28, DOI: 10.1016/j.ophtha.2021.01.003Reply: Anders Wåhlin, Petter Holmlund, Abigail M. Fellows, Jan Malm, Jay C. Buckey, Anders Eklund, Reply, Ophthalmology, Volume 128, Issue 5, 2021, Page e28. DOI: 10.1016/j.ophtha.2021.01.004

Background and purpose: A carotid stenosis can have a profound impact on the cerebral hemodynamics that cannot be inferred from the degree of stenosis by itself. We aimed to quantify and map the distribution of blood flow rate (BFR) in cerebral arteries before and after carotid endarterectomy (CEA), using four-dimensional phase-contrast magnetic resonance imaging (4D PCMRI). Methods: Nineteen patients (71±6 years, 2 women) with symptomatic carotid stenosis (≥50%)undergoing CEA were investigated using 4D PCMRI before and after surgery. BFR was measured in 17 cerebral arteries and in the ophthalmic arteries (OA). Collateral recruitment through the anterior and posterior communicating arteries, OA and the leptomeningeal arterial route was identified and quantified. BFR laterality was described as contralateral BFR minus ipsilateral BFR in paired arteries. Results: Total cerebral blood flow increased by 15% (p<0.01) after CEA. On the ipsilateral side, increased BFR was found after CEA in internal carotid artery (ICA) (246±62mL/min vs. 135±80mL/min; p<0.001), anterior cerebral artery (87±mL/min vs. 38±58mL/min; p<0.01) and middle cerebral artery (MCA) (149±43mL/min vs. 119±34mL/min; p<0.01), resulting in a postoperative BFR distribution without signs of laterality. In patients with preoperatively recruited collaterals (n=9), BFR laterality was found in MCA before, but not after, CEA (p<0.01). This laterality was not found in patients without collateral recruitment (n=10) (p=0.2). The degree of stenosis did not differ between the groups with vs. without collateral recruitment (p=0.85). Conclusion: 4D PCMRI is a useful technique to quantify cerebral hemodynamic changes seen in patients with carotid stenosis before and after CEA. MCA laterality, seen in patients with collateral recruitment before CEA, pointed towards a hemodynamic disturbance in MCA territory for those patients. This study introduces a new and non-invasive way to evaluate cerebral hemodynami, Originally included in thesis in manuscript form with title "Quantification and mapping of cerebral hemodynamics before and after carotid endarterectomy: a 4D PCMRI study"

Refers to: Re: Lindén et al.: Normal-tension glaucoma has normal intracranial pressure: a prospective study of intracranial pressure and intraocular pressure in different body positions (Ophthalmology. 2018;125:361-368)Ophthalmology, Volume 125, Issue 10, October 2018, Pages e74Xiangxiang Liu, Diya Yang, Yiquan Yang, Hanruo Liu, Xiaoxia Li, Yuan Xie, Ningli Wang. DOI: 10.1016/j.ophtha.2018.04.027

Supplement: 1 Meeting Abstract: PS03-082

Background: Intracranial pressure (ICP) is directly related to cranial dural venous pressure (P-dural). In the upright posture, P-dural is affected by the collapse of the internal jugular veins (IJVs) but this regulation of the venous pressure has not been fully understood. A potential biomechanical description of this regulation involves a transmission of surrounding atmospheric pressure to the internal venous pressure of the collapsed IJVs. This can be accomplished if hydrostatic effects are cancelled by the viscous losses in these collapsed veins, resulting in specific IJV cross-sectional areas that can be predicted from flow velocity and vessel inclination. Methods: We evaluated this potential mechanism in vivo by comparing predicted area to measured IJV area in healthy subjects. Seventeen healthy volunteers (age 45 +/- 9 years) were examined using ultrasound to assess IJV area and flow velocity. Ultrasound measurements were performed in supine and sitting positions. Results: IJV area was 94.5 mm(2) in supine and decreased to 6.5 +/- 5.1 mm(2) in sitting position, which agreed with the predicted IJV area of 8.7 +/- 5.2 mm(2) (equivalence limit +/- 5 mm(2), one-sided t tests, p = 0.03, 33 IJVs). Conclusions: The agreement between predicted and measured IJV area in sitting supports the occurrence of a hydrostatic-viscous pressure balance in the IJVs, which would result in a constant pressure segment in these collapsed veins, corresponding to a zero transmural pressure. This balance could thus serve as the mechanism by which collapse of the IJVs regulates P-dural and consequently ICP in the upright posture.

BACKGROUND: Three different types of anti-siphon devices (ASDs) have been developed to counteract siphoning-induced overdrainage in upright posture. However, it is not known how the different ASDs affect CSF dynamics under the complex pressure environment seen in clinic due to postural changes. We investigated which ASDs can avoid overdrainage in upright posture best without leading to CSF accumulation. METHODS: Three shunts each of the types Codman Hakim with SiphonGuard (flow-regulated), Miethke miniNAV with proSA (gravitational), and Medtronic Delta (membrane controlled) were tested. The shunts were compared on a novel in vitro setup that actively emulates the physiology of a shunted patient. This testing method allows determining the CSF drainage rates, resulting CSF volume, and intracranial pressure in the supine, sitting, and standing posture. RESULTS: The flow-regulated ASDs avoided increased drainage by closing their primary flow path when drainage exceeded 1.39 ± 0.42 mL/min. However, with intraperitoneal pressure increased in standing posture, we observed reopening of the ASD in 3 out of 18 experiment repetitions. The adjustable gravitational ASDs allow independent opening pressures in horizontal and vertical orientation, but they did not provide constant drainage in upright posture (0.37 ± 0.03 mL/min and 0.26 ± 0.03 mL/min in sitting and standing posture, respectively). Consequently, adaptation to the individual patient is critical. The membrane-controlled ASDs stopped drainage in upright posture. This eliminates the risk of overdrainage, but leads to CSF accumulation up to the volume observed without shunting when the patient is upright. CONCLUSIONS: While all tested ASDs reduced overdrainage, their actual performance will depend on a patient's specific needs because of the large variation in the way the ASDs influence CSF dynamics: while the flow-regulated shunts provide continuous drainage in upright posture, the gravitational ASDs allow and require a

Improved whole brain angiographic and velocity-sensitive MRI is pushing the boundaries of noninvasively obtained cerebral vascular flow information. The complexity of the information contained in such datasets calls for automated algorithms and pipelines, thus reducing the need of manual analyses by trained radiologists. The objective of this work was to lay the foundation for such automated pipelining by constructing and evaluating a probabilistic atlas describing the shape and location of the major cerebral arteries. Specifically, we investigated how the implementation of a non-linear normalization into Montreal Neurological Institute (MNI) space improved the alignment of individual arterial branches. In a population-based cohort of 167 subjects, age 64-68 years, we performed 4D flow MRI with whole brain volumetric coverage, yielding both angiographic and anatomical data. For each subject, sixteen cerebral arteries were manually labeled to construct the atlas. Angiographic data were normalized to MNI space using both rigid-body and non-linear transformations obtained from anatomical images. The alignment of arterial branches was significantly improved by the non-linear normalization (p < 0.001). Validation of the atlas was based on its applicability in automatic arterial labeling. A leave-one-out validation scheme revealed a labeling accuracy of 96 %. Arterial labeling was also performed in a separate clinical sample (n = 10) with an accuracy of 92.5 %. In conclusion, using non-linear spatial normalization we constructed an artery-specific probabilistic atlas, useful for cerebral arterial labeling.

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.

Measurement of intracranial pressure (ICP) is necessary in many neurological and neurosurgical diseases. To avoid lumbar puncture or intracranial ICP probes, non-invasive ICP techniques are becoming popular. A recently developed technology uses two-depth Doppler to compare arterial pulsations in the intra- and extra-cranial segments of the ophthalmic artery for non-invasive estimation of ICP. The aim of this study was to investigate how well non-invasively-measured ICP and invasively-measured cerebrospinal fluid (CSF) pressure correlate. We performed multiple measurements over a wide ICP span in eighteen elderly patients with communicating hydrocephalus. As a reference, an automatic CSF infusion apparatus was connected to the lumbar space. Ringer's solution was used to create elevation to pre-defined ICP levels. Bench tests of the infusion apparatus showed a random error (95 % CI) of less than ±0.9 mmHg and a systematic error of less than ±0.5 mmHg. Reliable Doppler signals were obtained in 13 (72 %) patients. An infusion test could not be performed in one patient. Thus, twelve patients and a total of 61 paired data points were studied. The correlation between invasive and non-invasive ICP measurements was good (R = 0.74), and the 95 % limits of agreements were -1.4 ± 8.8 mmHg. The within-patient correlation varied between 0.47 and 1.00. This non-invasive technique is promising, and these results encourage further development and evaluation before the method can be recommended for use in clinical practice.

BACKGROUND: More than half of astronauts develop ophthalmic changes during long-duration spaceflight consistent with an abnormal intraocular and intracranial pressure (IOP, ICP) difference. The aim of our study was to assess IOP and ICP during head-down tilt (HDT) and the additive or attenuating effects of 1% CO2 and lower body negative pressure (LBNP). METHODS: In Experiment I, IOP and ICP were measured in nine healthy subjects after 3.5 h HDT in five conditions: -6 degrees, -12 degrees, and -18 degrees HDT, -12 degrees with 1% CO2, and -12 degrees with -20 mmHg LBNP. In Experiment II, IOP was measured in 16 healthy subjects after 5 min tilt at +12 degrees, 0 degrees, -6 degrees, -12 degrees, -18 degrees, and -24 degrees, with and without-40 mmHg LBNP. RESULTS: ICP was only found to increase from supine baseline during -18 degrees HDT (9.2 +/- 0.9 and 14.4 +/- 1 mmHg, respectively), whereas IOP increased from 15.7 +/- 0.3 mmHg at 0 degrees to 17.9 +/- 0.4 mmHg during -12 degrees HDT and from 15.3 +/- 0.4 mmHg at 0 degrees to 18.7 +/- 0.4 mmHg during-18 degrees HDT. The addition of -20 mmHg LBNP or 1% CO2 had no further effects on ICP or IOP. However, the use of -40 mmHg LBNP during HDT lowered IOP back to baseline values, except at 24 degrees HDT. DISCUSSION: A small, posterior intraocular-intracranial pressure difference (IOP > ICP) is maintained during HDT, and a sustained or further decreased difference may lead to structural changes in the eye in real and simulated microgravity.

Background: Neuropathologically, Alzheimer's disease (AD) is characterized by accumulation of a 42 amino acid peptide called amyloid-beta (A beta(42)) in extracellular senile plaques together with intraneuronal inclusions of hyperphosphorylated tau protein in neurofibrillary tangles and neuronal degeneration. These changes are reflected in the cerebrospinal fluid (CSF), the volumes and production rates of which vary considerably between individuals, by reduced concentration of A beta(42), increased concentration of phosphorylated tau (P-tau) protein, and increased concentration of total tau (T-tau) protein, respectively. Objective: To examine the outstanding question if CSF concentrations of AD associated biomarkers are influenced by variations in CSF volumes, CSF production rate, and intracranial pressure in healthy individuals. Methods: CSF concentrations of A beta(42), P-tau, and T-tau, as well as a number of other AD-related CSF biomarkers were analyzed together with intracranial subarachnoid, ventricular, and spinal CSF volumes, as assessed by magnetic resonance imaging volumetric measurements, and CSF production rate in 19 cognitively normal healthy subjects (mean age 70.6, SD 3.6 years). Results: Negative correlations were seen between the concentrations of three CSF biomarkers (albumin ratio, A beta(38), and A beta(40)), and ventricular CSF volume, but apart from this finding, no significant correlations were observed. Conclusion: These results speak against inter-individual variations in CSF volume and production rate as important confounds in the AD biomarker research field.

Objective: To assess the complete vascular risk factor (VRF) profile of idiopathic normal pressure hydrocephalus (INPH) using a large sample of representative patients with INPH and populationbased controls to determine the extent to which vascular disease influences INPH pathophysiology. Methods: All patients with INPH who underwent shunting in Sweden in 2008-2010 were compared to age-and sex-matched population-based controls. Inclusion criteria were age 60-85 years and no dementia. The 10 most important VRFs and cerebrovascular and peripheral vascular disease were prospectively assessed using blood samples, clinical examinations, and standardized questionnaires. Assessed VRFs were hypertension, hyperlipidemia, diabetes, obesity, psychosocial factors, smoking habits, diet, alcohol intake, cardiac disease, and physical activity. Results: In total, 176 patients with INPH and 368 controls participated. Multivariable logistic regression analysis indicated that hyperlipidemia (odds ratio [OR] 2.380; 95% confidence interval [CI] 1.434-3.950), diabetes (OR 2.169; 95% CI 1.195-3.938), obesity (OR 5.428; 95% CI 2.502-11.772), and psychosocial factors (OR 5.343; 95% CI 3.219-8.868) were independently associated with INPH. Hypertension, physical inactivity, and cerebrovascular and peripheral vascular disease were also overrepresented in INPH. Moderate alcohol intake and physical activity were overrepresented among the controls. The population-attributable risk percentage was 24%. Conclusions: Our findings confirm that patients with INPH have more VRFs and lack the protective factors present in the general population. Almost 25% of cases of INPH may be explained by VRFs. This suggests that INPH may be a subtype of vascular dementia. Targeted interventions against modifiable VRFs are likely to have beneficial effects on INPH.

Background: A vascular disease could be involved in pathophysiology of normal pressure hydrocephalus (INPH). If so, there should be an association between INPH and cerebral microbleeds (CMB). This study aims to analyze if CMB are associated with INPH. Methods: In this case-control study we included 14 patients with INPH (mean age 76 years, 60 % female) and 41 healthy controls (HeCo; mean age 71 years, 60 % female). All were investigated with magnetic resonance imaging (MRI) using a T2*-sequence. The MRI exams were reviewed by two neuroradiologists for the presence of CMBs; the prevalence of findings of two or more CMBs was compared between INPH group and control group. After investigation, INPH patients underwent shunt surgery. Results: Two or more CMB were detected more frequently in the INPH group compared to HeCo (n = 6, 43 % vs. n = 4, 10 %; p = 0.01). Among the participants where MRI revealed CMB, the number of CMB was higher among the INPH patients than the HeCo (median 8; IQR 2-34 vs. median 1; IQR 1-2; p = 0.005). Conclusions: This study supports a vascular component to the pathophysiology of INPH.

Excessive pulsatile flow caused by aortic stiffness is thought to be a contributing factor for several cerebrovascular diseases. The main purpose of this study was to describe the dampening of the pulsatile flow from the proximal to the distal cerebral arteries, the effect of aging and sex, and its correlation to aortic stiffness. Forty-five healthy elderly (mean age 71 years) and 49 healthy young (mean age 25 years) were included. Phase-contrast magnetic resonance imaging was used for measuring blood flow pulsatility index and dampening factor (proximal artery pulsatility index/distal artery pulsatility index) in 21 cerebral and extra-cerebral arteries. Aortic stiffness was measured as aortic pulse wave velocity. Cerebral arterial pulsatility index increased due to aging and this was more pronounced in distal segments of cerebral arteries. There was no difference in pulsatility index between women and men. Dampening of pulsatility index was observed in all cerebral arteries in both age groups but was significantly higher in young subjects than in elderly. Pulse wave velocity was not correlated with cerebral arterial pulsatility index. The increased pulsatile flow in elderly together with reduced dampening supports the pulse wave encephalopathy theory, since it implies that a higher pulsatile flow is reaching distal arterial segments in older subjects.

The pathophysiology of acute mountain sickness and high-altitude cerebral edema, the cerebral forms of high-altitude illness, remain uncertain and controversial. Persistently elevated or pathological fluctuations in intracranial pressure are thought to cause symptoms similar to those reported by individuals suffering cerebral forms of high-altitude illness. This review first focuses on the basic physiology of the craniospinal system, including a detailed discussion of the long-term and dynamic regulation of intracranial pressure. Thereafter, we critically examine the available literature, based primarily on invasive pressure monitoring, that suggests intracranial pressure is acutely elevated at altitude due to brain swelling and/or elevated sagittal sinus pressure, but normalizes over time. We hypothesize that fluctuations in intracranial pressure occur around a slightly elevated or normal mean intracranial pressure, in conjunction with oscillations in arterial PO2 and arterial blood pressure. Then these modest fluctuations in intracranial pressure, in concert with direct vascular stretch due to dilatation and/or increased blood pressure transmission, activate the trigeminal vascular system and cause symptoms of acute mountain sickness. Elevated brain water (vasogenic edema) may be due to breakdown of the blood-brain barrier. However, new information suggests cerebral spinal fluid flux into the brain may be an important factor. Regardless of the source (or mechanisms responsible) for the excess brain water, brain swelling occurs, and a "tight fit" brain would be a major risk factor to produce symptoms; activities that produce large changes in brain volume and cause fluctuations in blood pressure are likely contributing factors.

BACKGROUND: If patients with idiopathic normal pressure hydrocephalus (INPH) also have depression, this could have important clinical ramifications in assessment and management of their cognitive function and response to shunting. In many dementias, depression is overrepresented, but the prevalence of depression in shunted patients with INPH is unknown. OBJECTIVE: The objective of this case-control study was to assess the prevalence of symptoms of depression in shunted INPH patients compared with population-based controls. METHODS: INPH patients consecutively shunted from 2008 to 2010 in Sweden were analyzed. Patients remaining after inclusion (within 60-85 years and not having dementia, ie, mini-mental state examination >=23) had a standardized visit to their healthcare provider and answered an extensive questionnaire. Age- and sex-matched population-based controls underwent the same procedure. Symptoms of depression were assessed using the Geriatric Depression Scale 15 (suspected depression defined as >=5 points, suspected severe depression as >=12 points). This study is part of the INPH-CRasH study. RESULTS: One hundred seventy-six INPH patients and 368 controls participated. After adjustment for age, sex, cerebrovascular disease, and systolic and diastolic blood pressure, patients had a higher mean depression score (patients: 4.9 ± 3.7 SD, controls: 1.9 ± 2.3 SD; OR 1.4, 95% CI 1.3-1.6, P < .001), more patients had suspected depression (46% vs 13%, OR 6.4, 95% CI 3.8-10.9, P < .001), and more patients had suspected severe depression (7.3% vs 0.6%, OR 14.4, 95% CI 3.0-68.6, P < .005). CONCLUSION: Symptoms of depression are overrepresented in INPH patients compared with the population, despite treatment with a shunt. Screening for depression should be done in the evaluation of INPH patients in order to find and treat a coexisting depression.

In order to introduce 4D flow magnetic resonance imaging (MRI) as a standard clinical instrument for studying the cerebrovascular system, new and faster postprocessing tools are necessary. The objective of this study was to construct and evaluate a method for automatic identification of individual cerebral arteries in a 4D flow MRI angiogram. Forty-six elderly individuals were investigated with 4D flow MRI. Fourteen main cerebral arteries were manually labeled and used to create a probabilistic atlas. An automatic atlas-based artery identification method (AAIM) was developed based on vascular-branch extraction and the atlas was used for identification. The method was evaluated by comparing automatic with manual identification in 4D flow MRI angiograms from 67 additional elderly individuals. Overall accuracy was 93 %, and internal carotid artery and middle cerebral artery labeling was 100 % accurate. Smaller and more distal arteries had lower accuracy; for posterior communicating arteries and vertebral arteries, accuracy was 70 and 89 %, respectively. The AAIM enabled fast and fully automatic labeling of the main cerebral arteries. AAIM functionality provides the basis for creating an automatic and powerful method to analyze arterial cerebral blood flow in clinical routine.

Background: There is a lack of effective treatment for neglect. We have developed a new training method, RehAtt (TM). The objective of this study was to determine whether RehAtt (TM) improves spatial attention in chronic neglect after stroke. Methods: RehAtt (TM) consists of a computer with monitor, 3D glasses, and a force feedback interface (Robotic pen) giving sensory motor activation to the contra-lesional arm. The software combines visual scanning training with multi-sensory stimulation in 3D virtual reality (VR) game environment. Fifteen stroke patients with chronic neglect (duration > 6 month) had repeated baseline evaluations to confirm stability of symptoms. There were no test-retest effects for any of the tests. Thereafter, all patients trained 15 h in RehAtt (TM) (3 x 1 h for 5 weeks). A neglect test battery and Catherine Bergego Scale, CBS, were used to assess behavioral outcome after intervention. CBS was also used at a 6-month follow-up. Results: Using repeated measurement analysis improvements due to the training were found for Star cancellation test (p = 0.006), Baking tray task (p < 0.001), and Extinction test (p = 0.05). In the Posner task improvements were seen fewer missed targets (p = 0.024). CBS showed improvements in activities of daily life immediately after training (p < 0.01). After 6 months the patients still reported improvement in CBS. Conclusion: RehAtt (TM) is a new concept for rehabilitation of neglect. Training with the VR-method improved spatial attention and showed transfer to improved spatial attention in activities of daily living in chronic neglect. Our results are promising and merit further studies.

Alterations in cerebral hemodynamics in microgravity are hypothesized to occur during spaceflight and could be linked to the Visual Impairment and Intracranial Pressure syndrome. Head-down tilt (HDT) is frequently used as a ground-based analog to simulate cephalad fluid shifts in microgravity; however, its effects on cerebral hemodynamics have not been well studied with MRI techniques. Here, we evaluate the effects of 1) various HDT angles on cerebral arterial and venous hemodynamics; and 2) exposure to 1% CO2 during an intermediate HDT angle (-12 degrees) as an additional space-related environmental factor. Blood flow, cross-sectional area (CSA), and blood flow velocity were measured with phase-contrast MRI in the internal jugular veins, as well as the vertebral and internal carotid arteries. Nine healthy male subjects were measured at baseline (supine, 0 degrees) and after 4.5 h of HDT at -6 degrees, -12 degrees (with and without 1% CO2), and -18 degrees. We found a decrease in total arterial blood flow from baseline during all angles of HDT. On the venous side, CSA increased with HDT, and outflow decreased during -12 degrees HDT (P = 0.039). Moreover, the addition of 1% CO2 to -12 degrees HDT caused an increase in total arterial blood flow (P = 0.016) and jugular venous outflow (P = 0.001) compared with -12 degrees HDT with ambient atmosphere. Overall, the results indicate decreased cerebral blood flow during HDT, which may have implications for microgravity-induced cerebral hemodynamic changes.

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 spi

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.

PurposeTo describe, validate, and implement a centerline processing scheme (CPS) for semiautomated segmentation and quantification in carotid siphons of healthy subjects. 4D flow MRI enables blood flow measurement in all major cerebral arteries with one scan. Clinical translational hurdles are time demanding postprocessing and user-dependence induced variability during analysis. Materials and MethodsA CPS for 4D flow data was developed to automatically separate cerebral artery trees. Flow parameters were quantified at planes along the centerline oriented perpendicular to the vessel path. At 3T, validation against 2D phase-contrast (PC) magnetic resonance imaging (MRI) and 4D flow manual processing was performed on an intracranial flow phantom for constant flow, while pulsatile flow validation was performed in the internal carotid artery (ICA) of 10 healthy volunteers. The CPS and 4D manual processing times were measured and compared. Flow and area measurements were also demonstrated along the length of the ICA siphon. ResultsPhantom measurements for area and flow were highly correlated between the CPS and 2D measurements (area: R=0.95, flow: R=0.94), while in vivo waveforms were highly correlated (R=0.93). Processing time was reduced by a factor of 4.6 compared with manual processing. Whole ICA measurements revealed a significantly decreased area in the most distal segment of the carotid siphon (P=0.0017), with flow unchanged (P=0.84). ConclusionThis study exhibits fast semiautomated analysis of intracranial 4D flow MRI. Internal consistency was shown through flow conservation along the tortuous ICA siphon, which is typically difficult to assess. J. Magn. Reson. Imaging 2015;42:1458-1464.

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. 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). 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. 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.

Purpose: To investigate aging effect on ocular parameters inkluding intraocular pressure (IOP) measured with different tonometry methods in healthy young (HY) and elderly (HE) subjects. Methods: Fifty eyes of 50 HY subjects (28 females, 22-31 years of age) and 43 eyes of 43 HE subjects (22 females, 64-79 years of age) 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), ocular pulse amplitude (OPA) and aqueous humor (aq). Results: The mean IOP (HY/HE; mmHg ± standard deviation) was 13.9 ± 2.7/16.4 ± 3.4 with ORA, 15.1 ± 2.1/16.3 ± 3.1 with DCT, 12.3 ± 2.0/13.7 ± 2.8 with GAT and 13.1 ± 2.2/12.1 ± 2.5 with ART. IOP was significantly higher (difference ± standard error) in HE compared to HY measured with ORA (+2.5 mmHg ± 0.6), GAT (+1.4 ± 0.5) and DCT (+1.2 ± 0.6). There was a trend towards lower IOP in HE when measured with ART (-1.0 ± 0.5, p=0.05). There was no difference between HE and HY in CCT, CC, AL or OPA. Conclusions: Tonometry methods are affected differently by age. IOP was measured higher in elderly people with ORA, DCT and GAT in this Scandinavian population. This effect was not seen in measurements with ART. Other ocular parameters did not differ between the age groups indicating that these measured parameters are not influenced by age in this population.

Arterial Spin labeling (ASL) is a fully non-invasive MRI method capable to quantify cerebral perfusion. However, gray (GM) and white matter (WM) ASL perfusions are difficult to assess separately due to limited spatial resolution increasing the partial volume effects (PVE). In the present study, ASL PVE correction was implemented based on a regression algorithm in 22 healthy young men. PVE corrected perfusion of GM and WM were compared to previous studies. PVE-corrected GM perfusion was in agreement with literature values. In general, WM perfusion was higher despite the use of PVE correction.

4D flow MRI is a powerful imaging technique which provides an angiographic image with information about blood flow in a large volume, time resolved over the cardiac cycle, in a short imaging time. This study aims to develop an automatic method for identification of cerebral arteries. The proposed method is based on an atlas of twelve arteries, developed from 4D flow MRI of 25 subjects. The atlas was constructed by normalizing all images to MNI-space, manually identifying the arteries and creating an average over the volume. The identification is done by extracting a vascular skeleton from the image, transforming it to MNI-space, labeling it with the atlas and transforming it back to subject space. The method was evaluated on a pilot cohort of 8 subjects. The rate of correctly identified arteries was 97%.

This prospective consecutive double-blinded randomized study investigated the effect of prostacyclin on pressure reactivity (PR) in severe traumatic brain injured patients. Other aims were to describe PR over time and its relation to outcome. Blunt head trauma patients, Glasgow coma scale a parts per thousand currency sign8, age 15-70 years were included and randomized to prostacyclin treatment (n = 23) or placebo (n = 25). Outcome was assessed using the extended Glasgow outcome scale (GOSE) at 3 months. PR was calculated as the regression coefficient between the hourly mean values of ICP versus MAP. Pressure active/stable was defined as PR a parts per thousand currency sign0. Mean PR over 96 h (PRtot) was 0.077 +/- A 0.168, in the prostacyclin group 0.030 +/- A 0.153 and in the placebo group 0.120 +/- A 0.173 (p < 0.02). There was a larger portion of pressure-active/stable patients in the prostacyclin group than in the placebo group (p < 0.05). Intra-individual changes over time were common. PRtot correlated negatively with GOSE score (p < 0.04). PRtot was 0.117 +/- A 0.182 in the unfavorable (GOSE 1-4) and 0.029 +/- A 0.140 in the favorable outcome group (GOSE 5-8). Area under the curve for prediction of death (ROC) was 0.742 and for favorable outcome 0.628. Prostacyclin influenced the PR in a direction of increased pressure stability and a lower PRtot was associated with improved outcome. The individual PR varied substantially over time. The predictive value of PRtot for outcome was not solid enough to be used in the clinical situation.

Purpose: Developmental characteristics of the neuronal adaptive system of the retina, focusing on background light (BGL) adaptation and readaptation functions, were studied by measuring the oscillatory response (SOP) of the electroretinogram (ERG). Methods: Digitally filtered and conventional ERGs were simultaneously recorded. Rats aged 15 and 17 days were studied during exposure to BGLs of two mesopic intensities and during readaptation to dark. Results: Results were compared to adult rats. In ‘low mesopic’ BGL SOP instantly dropped significantly to about half of its dark-adapted (DA) value contrary to mature rats, in which the SOP significantly increased. In ‘high mesopic’ BGL SOP decreased to about 20% and 30% of DA values in immature and adult rats, respectively. The process of recovery of SOP in darkness lacked the transient enhancement immediately as BGL was turned off, characteristic of adult rats. There were no major age differences in adaptive behaviour of a-wave. In young rats, recovery of b-wave was relatively slower. Conclusions: Properties of BGL adaptation and readaptation functions of the neuronal adaptive system in baby retina differed compared to the adult one by being less forceful and more restrained. Handling of mesopic illumination and recovery in the dark was immature. Development of these functions of the neuronal adaptive system progresses postnatally and lags behind that of the photoreceptor response and seems to be delayed also compared to that of the bipolar response.

BACKGROUND: A tool for standardized and repeated neuropsychological assessments in patients with idiopathic normal pressure hydrocephalus (INPH) is needed. The objective of this study was to develop a computerized neuropsychological test battery designed for INPH and to evaluate its reliability, validity and patient's ability to complete the tests. METHODS: Based on a structured review of the literature on neuropsychological testing in INPH, the eight tests most sensitive to the INPH cognitive profile were implemented in a computerized format. The Geriatric Depression Scale (GDS) was also included. Tests were presented on a touch-screen monitor, with animated instructions and speaker sound. The battery was evaluated with the following cohorts: A. Test-retest reliability, 44 healthy elderly; B. Validity against standard pen and pencil testing, 28 patients with various cognitive impairments; C. Ability to complete test battery, defined as completion of at least seven of the eight tests, 40 investigated for INPH. RESULTS: A. All except the figure copy test showed good test-retest reliability, r = 0.67-0.90; B. A high correlation was seen between conventional and computerized tests (r = 0.66-0.85) except for delayed recognition and figure copy task; C. Seventy-eight percent completed the computerized battery; Patients diagnosed with INPH (n = 26) performed worse on all tests, including depression score, compared to healthy controls. CONCLUSIONS: A new computerized neuropsychological test battery designed for patients with communicating hydrocephalus and INPH was introduced. Its reliability, validity for general cognitive impairment and completion rate for INPH was promising. After exclusion of the figure copy task, the battery is ready for clinical evaluation and as a next step we suggest validation for INPH and a comparison before and after shunt surgery. TRIAL REGISTRATION: ClinicalTrials.org NCT01265251.

Excessive intracranial pulsatility is thought to damage the cerebral microcirculation, causing cognitive decline in elderly individuals. We investigated relationships between brain structure and measures related to intracranial pulsatility among healthy elderly. Thirty-seven stroke-free, non-demented individuals (62-82 years of age) were included. We assessed brain structure, invasively measured cerebrospinal fluid (CSF) pulse pressure, and magnetic resonance-quantified arterial and CSF flow pulsatility, as well as arterial pulse pressure. Using both multivariate partial least squares and ordinary regression analyses, we identified a significant pattern of negative relationships between the volume of several brain regions and measures of intracranial pulsatility. The strongest relationships concerned the temporal lobe cortex and hippocampus. These findings were also coherent with observations of positive relationships between intracranial pulsatility and ventricular volume. In conclusion, elderly subjects with high intracranial pulsatility display smaller brain volume and larger ventricles, supporting the notion that excessive cerebral arterial pulsatility harms the brain. This calls for research investigating altered intracranial cardiac-related pulsatile stress as a potential risk factor that may cause or worsen the prognosis in subjects developing cognitive impairment and dementia.

This paper reports a novel MEMS valve with adaptive flow characteristics for improved treatment of hydrocephalus, a disease that is characterized by elevated pressure in the cerebrospinal fluid (CSF) that surrounds the brain and spinal cord. In contrast to conventional valves with two ports, the valve presented here features a third port, called compensation port, which utilizes hydrostatic pressure to adapt CSF drainage based on body position. A prototype has been fabricated using standard MEMS manufacturing processes and the experimental evaluation successfully showed that the flow rate was adjustable with a varying hydrostatic pressure on the compensation port. Extracted data shows that flow rate was at near ideal values at both standing and laying body position showing an effective adaptation to body position. This is the first passive hydrocephalus valve intended for body position dependent CSF pressure regulation. © 2013 IEEE.

Object There are several infusion methods available to estimate the outflow conductance (Cout) or outflow resistance (Rout = 1/Cout) of the CSF system. It has been stated that for unknown reasons, the bolus infusion method estimates a higher Cout than steady-state infusion methods. The aim of this study was to compare different infusion methods for estimation of Cout. Methods The following 3 different infusion methods were used: the bolus infusion method (Cout bol); the constant flow infusion method, both static (Cout stat) and dynamic (Cout dyn) analyses; and the constant pressure infusion method (Cout cpi). Repeated investigations were performed on an experimental model with well-known characteristics, with and without physiological pressure variations (B-waves, breathing, and so on). All 3 methods were also performed in a randomized order during the same investigation in 20 patients with probable or possible idiopathic normal-pressure hydrocephalus; 6 of these patients had a shunt and 14 did not. Results Without the presence of physiological pressure variations, the concordance in the experimental model was good between all methods. When they were added, the repeatability was better for the steady-state methods and a significantly higher Cout was found with the bolus method in the region of clinically relevant Cout (p < 0.05). The visual fit for the bolus infusion was dependent on subjective assessment by the operator. This experimental finding was confirmed by the clinical results, where significant differences were found in the investigations in patients without shunts between Cout of the visual bolus method and Cout stat, Cout dyn, and Cout cpi (4.58, 4.18, and 6.12 μl/[second × kPa], respectively). Conclusions This study emphasized the necessity for standardization of Cout measurements. An experienced operator could partly compensate for difficulties in correctly estimating the pressure parameters for the bolus infusion method, but for the general user thi, Publicerades i Nina Anderssons (=Nina Sundströms) avhandling som ett manuskript med titel:Does the cerebrospinal fluid outflow conductance determined by steady state infusion methods differ from that of the bolus infusion method?

Outflow conductance (C out) is important for predicting shunt responsiveness in patients with suspected idiopathic adult hydrocephalus syndrome (IAHS). C out is determined by performing an infusion test into the cerebrospinal fluid system, and the reliability of the test is dependent on the measurement time. The objective of this study was to develop an adaptive signal analysis method to reduce the investigation time, by taking the individual intracranial pressure variations of the patient into consideration. The method was evaluated on 28 patients with suspected IAHS. The results from full time investigations (60 min) were compared to the results of the new algorithm. Applying the new adaptive method resulted in a reduction of mean investigation time by 14.3 ± 5.9 min (mean ± SD), p < 0.01. The reduction of reliability in the C out estimation was found clinically negligible. We thus recommend this adaptive method to be used when performing constant pressure infusion tests.

Applanation resonance tonometry (ART) has been shown in a number of studies to be useful for measuring intraocular pressure (IOP). Data from in vitro laboratory bench testing, where the sensor was carefully centralised onto the cornea, has been very consistent with good precision in the determination of IOP. However, in a clinical study the unavoidable off-centre placement of the sensor against the cornea resulted in a reduced precision. The aim of this study was to evaluate a new design of the sensor with a symmetric sensor probe and a contact piece with a larger diameter. Two in vitro porcine eye experimental set-ups were used. One bench-based for examining position dependence and one biomicroscope-based set-up, simulating a clinical setting, for evaluating IOP(ART) precision at seven different pressure levels (1040 mmHg), set by connecting a saline column to the vitreous chamber. The reference IOP was recorded using a pressure transducer. There was no significant difference between four positions 1 mm off centre and the one centre position. The precision of the ART as compared with the reference pressure was +/- 1.03 mmHg (SD, n = 42). The design improvement has enhanced the precision of the ART in the biomicroscope set-up to be in parity with bench test results from a set-up using perfect positioning. This indicates that off-centre positioning was no longer a major contributor to the deviations in measured IOP. The precision was well within the limits set by ISO standard for eye tonometers. Therefore, a larger in vivo study on human eyes with the ART should be performed.

Excimer laser surgery, to correct corneal refraction, induces changes in corneal thickness and curvature. Both factors can cause measurement errors when determining intraocular pressure (IOP). This study evaluates effects of photorefractive keratectomy (PRK) on IOP measurements, using Goldmann applanation tonometry (GAT) and Applanation resonance tonometry (ART), in an in vitro model. Six porcine eyes was enucleated and pressurised to a constant IOP=30 mmHg. After removal of the epithelium, the eyes were PRK-treated for a total of 25 dioptres. The measured IOP decreased 13.2 mmHg for GAT and 9.0 mmHg for ART. The total underestimation by GAT was larger than for ART, and a part of the ART underestimation (3.5 mmHg) was assigned to sensitivity to the change in corneal surface structure resulting from the removal of epithelium. The flat contact probe of GAT, as compared with the convex tip of ART, provided explanation for the difference in IOP measurement error after PRK.

Background: B waves, slow and rhythmic oscillations in intracranial pressure (ICP), are claimed to be one of the best predictors of outcome after surgery for normal pressure hydrocephalus (NPH). Object: To determine the relation between the percentage of B waves and outcome in patients with hydrocephalus, and also the diurnal variation of B waves. Methods: ICP and patient behaviour were recorded overnight (17 to 26 hours) in 29 patients with non-communicating hydrocephalus and 26 with NPH. The B wave activity, measured with an amplitude threshold of 0.5, 0.75, 1.0, 1.5, 2.0, 3.0, and 5.0 mm Hg, was estimated as the percentage of total monitoring time (% B waves) using a computer algorithm, and correlated with postoperative outcome, defined as changes in 12 standardised symptoms and signs. Results: There was no linear correlation between improvement after surgery in the 55 patients and total % B waves, but a correlation was found between improvement and % B waves during sleep (r = 0.39, p = 0.04). The percentage of B waves was the same during sleep and wakefulness, and patients with NPH had the same proportion of B waves as the non-communicating patients. Conclusions: B waves are commonly observed in patients with both communicating and non-communicating hydrocephalus, but are only weakly related to the degree of postsurgical improvement.

BACKGROUND: The symptoms in idiopathic adult hydrocephalus syndrome (IAHS) are consistent with pathology involving the periventricular white matter, presumably reflecting ischaemia and CSF hydrodynamic disturbance. OBJECTIVE: To investigate whether a change in intracranial pressure (ICP) can affect energy metabolism in deep white matter. METHODS: A microdialysis catheter, a brain tissue oxygen tension probe, and an ICP transducer were inserted into the periventricular white matter 0-7 mm from the right frontal horn in 10 patients with IAHS. ICP and intracerebral Ptio2 were recorded continuously during lumbar CSF constant pressure infusion test. ICP was raised to pressure levels of 35 and 45 mm Hg for 10 minutes each, after which CSF drainage was undertaken. Microdialysis samples were collected every three minutes and analysed for glucose, lactate, pyruvate, and glutamate. RESULTS: When raising the ICP, a reversible drop in the extracellular concentrations of glucose, lactate, and pyruvate was found. Comparing the values during baseline to values at the highest pressure level, the fall in glucose, lactate, and pyruvate was significant (p < 0.05, Wilcoxon sign rank). There was no change in glutamate or the lactate to pyruvate ratio during ICP elevation. Ptio2 did not decrease during ICP elevation, but was significantly increased following CSF drainage. CONCLUSIONS: Raising intracranial pressure induces an immediate and reversible change in energy metabolism in periventricular white matter, without any sign of ischaemia. Theoretically, frequent ICP peaks (B waves) over a long period could eventually cause persisting axonal disturbance and subsequently the symptoms noted in IAHS.