Current Understanding of the Anatomy, Physiology, and Magnetic Resonance Imaging of Neurofluids: Update From the 2022 "ISMRM Imaging Neurofluids Study group" Workshop in Rome.

Neurofluids is a term introduced to define all fluids in the brain and spine such as blood, cerebrospinal fluid, and interstitial fluid. Neuroscientists in the past millennium have steadily identified the several different fluid environments in the brain and spine that interact in a synchronized harmonious manner to assure a healthy microenvironment required for optimal neuroglial function. Neuroanatomists and biochemists have provided an incredible wealth of evidence revealing the anatomy of perivascular spaces, meninges and glia and their role in drainage of neuronal waste products. Human studies have been limited due to the restricted availability of noninvasive imaging modalities that can provide a high spatiotemporal depiction of the brain neurofluids. Therefore, animal studies have been key in advancing our knowledge of the temporal and spatial dynamics of fluids, for example, by injecting tracers with different molecular weights. Such studies have sparked interest to identify possible disruptions to neurofluids dynamics in human diseases such as small vessel disease, cerebral amyloid angiopathy, and dementia. However, key differences between rodent and human physiology should be considered when extrapolating these findings to understand the human brain. An increasing armamentarium of noninvasive MRI techniques is being built to identify markers of altered drainage pathways. During the three-day workshop organized by the International Society of Magnetic Resonance in Medicine that was held in Rome in September 2022, several of these concepts were discussed by a distinguished international faculty to lay the basis of what is known and where we still lack evidence. We envision that in the next decade, MRI will allow imaging of the physiology of neurofluid dynamics and drainage pathways in the human brain to identify true pathological processes underlying disease and to discover new avenues for early diagnoses and treatments including drug delivery. Evidence level: 1 Technical Efficacy: Stage 3.

CSF-to-blood toxins clearance is modulated by breathing through cranio-spinal CSF oscillation.

Clearance of brain toxins occurs during sleep, although the mechanism remains unknown. Previous studies implied that the intracranial aqueductal cerebrospinal fluid (CSF) oscillations are involved, but no mechanism was suggested. The rationale for focusing on the aqueductal CSF oscillations is unclear. This study focuses on the cranio-spinal CSF oscillation and the factors that modulate this flow. We propose a mechanism where increased cranio-spinal CSF movements enhance CSF-to-blood metabolic waste clearance through the spinal CSF re-absorption sites. A recent study demonstrating that disturbed sleep impairs CSF-to-blood but not brain-to-CSF clearance, supports the fundamentals of our proposed mechanism. Eight healthy subjects underwent phase-contrast magnetic resonance imaging to quantify the effect of respiration on the cranio-spinal CSF oscillations. Maximal CSF volume displaced from the cranium to the spinal canal during each respiration and cardiac cycle were derived as measures of cranio-spinal CSF mixing level. Transition from normal to slow and abdominal breathing resulted in a 56% increase in the maximal displaced CSF volume. Maximal change in the arterial-venous blood volume, which is the driving force of the CSF oscillations, was increased by 41% during slow abdominal breathing. Cranio-spinal CSF oscillations are driven by the momentary difference between arterial inflow and venous outflow. Breathing modulates the CSF oscillation through changes in the venous outflow. The amount of toxins being transferred to the spinal canal during each respiratory cycle is significantly increased during slow and deeper abdominal breathing, which explains enhanced CSF-to-blood toxins clearance during slow-wave sleep and poor clearance during disrupted sleep.

Poor sleep accelerates hippocampal and posterior cingulate volume loss in cognitively normal healthy older adults.

Poor sleep quality is a known risk factor for Alzheimer's disease. This longitudinal imaging study aimed to determine the acceleration in the rates of tissue loss in cognitively critical brain regions due to poor sleep in healthy elderly individuals. Cognitively-normal healthy individuals, aged ≥60 years, reported Pittsburgh Sleep Quality Index (PSQI) and underwent baseline and 2-year follow-up magnetic resonance imaging brain scans. The links between self-reported sleep quality, rates of tissue loss in cognitively-critical brain regions, and white matter hyperintensity load were assessed. A total of 48 subjects were classified into normal (n = 23; PSQI score <5) and poor sleepers (n = 25; PSQI score ≥5). The two groups were not significantly different in terms of age, gender, years of education, ethnicity, handedness, body mass index, and cognitive performance. Compared to normal sleepers, poor sleepers exhibited much faster rates of volume loss, over threefold in the right hippocampus and fivefold in the right posterior cingulate over 2 years. In contrast, there were no significant differences in the rates of volume loss in the cerebral and cerebellar grey and white matter between the two groups. Rates of volume loss in the right posterior cingulate were negatively associated with global PSQI scores. Poor sleep significantly accelerates volume loss in the right hippocampus and the right posterior cingulate cortex. These findings demonstrate that self-reported sleep quality explains inter-individual differences in the rates of volume loss in cognitively-critical brain regions in healthy older adults and provide a strong impetus to offer sleep interventions to cognitively normal older adults who are poor sleepers.

Structural Basal Ganglia Correlates of Subjective Fatigue in Middle-Aged and Older Adults.

OBJECTIVE: Fatigue is among the most common complaints in community-dwelling older adults, yet its etiology is poorly understood. Based on models implicating frontostriatal pathways in fatigue pathogenesis, we hypothesized that smaller basal ganglia volume would be associated with higher levels of subjective fatigue and reduced set-shifting in middle-aged and older adults without dementia or other neurologic conditions. METHODS: Forty-eight non-demented middle-aged and older adults (Mage = 68.1, SD = 9.4; MMMSE = 27.3, SD = 1.9) completed the Fatigue Symptom Inventory, set-shifting measures, and structural MRI as part of a clinical evaluation for subjective cognitive complaints. Associations were examined cross-sectionally. RESULTS: Linear regression analyses showed that smaller normalized basal ganglia volumes were associated with more severe fatigue (ß = -.29, P = .041) and poorer Trail Making Test B-A (TMT B-A) performance (ß = .30, P = .033) controlling for depression, sleep quality, vascular risk factors, and global cognitive status. Putamen emerged as a key structure linked with both fatigue (r = -.43, P = .003) and TMT B-A (ß = .35, P = .021). The link between total basal ganglia volume and reduced TMT B-A was particularly strong in clinically fatigued patients. CONCLUSION: This study is among the first to show that reduced basal ganglia volume is an important neurostructural correlate of subjective fatigue in physically able middle-aged and older adults without neurological conditions. Findings suggest that fatigue and rapid set-shifting deficits may share common neural underpinnings involving the basal ganglia, and provide a framework for studying the neuropathogenesis and treatment of subjective fatigue.

Role of the spinal canal compliance in regulating posture-related cerebrospinal fluid hydrodynamics in humans.

Mechanical compliance of a compartment is defined by the change in its volume with respect to a change in the inside pressure. The compliance of the spinal canal regulates the intracranial pressure (ICP) under postural changes. Understanding how gravity affects ICP is beneficial for poorly understood cerebrospinal fluid (CSF)-related disorders. The aim of this study was to evaluate postural effects on cranial hemo- and hydrodynamics. This was a prospective study, which included 10 healthy volunteers (three males, seven females, mean ± standard deviation age: 29 ± 7 years). Cine gradient-echo phase-contrast sequence acquired at 0.5 T, "GE double-doughnut" scanner was used. Spinal contribution to overall craniospinal compliance (CSC), craniospinal CSF stroke volume (SV), magnetic resonance (MR)-derived ICP (MR-ICP), and total cerebral blood flow (TCBF) were measured in supine and upright postures using automated blood and CSF flows quantification. Statistical tests performed were two-sided Student's t-test, Cohen's d, and Pearson correlation coefficient. MR-ICP and the craniospinal CSF SV were significantly correlated with the spinal contribution to the overall CSC (r = 0.83, p < 0.05) and (r = 0.62, p < 0.05), respectively. Cranial contribution to CSC increased from 44.5% ± 16% in supine to 74.9% ± 8.4% in upright posture. The average MR-ICP dropped from 9.9 ± 3.4 mmHg in supine to -3.5 ± 1.5 mmHg. The CSF SV was over 2.5 times higher in the supine position (0.55 ± 0.14 ml) than in the upright position (0.21 ± 0.13 ml). In contrast, TCBF was slightly higher in the supine posture (822 ± 152 ml/min) than in the upright posture (761 ± 139 ml/min), although not statistically significant (p = 0.16). The spinal-canal compliance contribution to CSC is larger than the cranial contribution in the supine posture and smaller in the upright posture. Thereby, the spinal canal plays a role in modulating ICP upon postural changes. The lower pressure craniospinal CSF system was more affected by postural changes than the higher-pressure cerebral vascular system. Craniospinal hydrodynamics is affected by gravity and is likely to be altered by its absence in space. LEVEL OF EVIDENCE: 4 TECHNICAL EFFICACY STAGE: 2.

Quantification of Regional Cerebral Blood Flow Using Diffusion Imaging With Phase Contrast.

BACKGROUND: The perfusion-related diffusion coefficient obtained from triexponential diffusion analysis is closely correlated with regional cerebral blood flow (rCBF), as assessed by arterial spin labeling (ASL) methods. However, this provides only a semiquantitative measure of rCBF, thereby making absolute rCBF quantification challenging. PURPOSE: To obtain rCBF in a noninvasive manner using a novel diffusion imaging method with phase contrast (DPC), in which the total CBF from phase-contrast (PC) MRI was utilized to convert perfusion-related diffusion coefficients to rCBF values. STUDY TYPE: Prospective. SUBJECTS: Eleven healthy volunteers (nine men and two women; mean age, 23.9 years) participated in this study. FIELD STRENGTH/SEQUENCE: A 3.0 T, single-shot diffusion echo-planar imaging with multiple b-values (0-3000 s/mm2 ), PC-MRI, pulsed continuous ASL, and 3D T1 -weighted fast field echo. ASSESSMENT: rCBF and its correlations in the gray matter (GM) and white matter (WM) were compared between DPC and ASL methods. rCBF in the GM and WM and the GM/WM ratio were compared with the literature values obtained using [15 O]-water positron emission tomography (15 O-H2 O PET). STATISTICAL TESTS: Spearman's correlation coefficient and Wilcoxon signed-rank test were used. Significance was set at P < 0.05. RESULTS: A significant positive correlation between DPC and ASL in terms of rCBF was observed in GM (R = 0.9), whereas the correlation between the two methods was poor in WM (R = 0.09). The rCBF in GM and WM and the GM/WM ratio obtained using DPC were consistent with the literature values assessed using 15 O-H2 O PET. The rCBF value obtained using DPC was significantly higher in the GM and WM than that using ASL. DATA CONCLUSION: DPC enabled noninvasive quantification of rCBF. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 1.

Poor sleep is associated with small hippocampal subfields in cognitively normal elderly individuals.

Recent studies demonstrated reduced hippocampal volumes in elderly healthy individuals who are cognitively normal but poor sleepers. The association between sleep quality and the pattern of volume loss across hippocampal subfields (HSs) is not well known. Thus, it is the focus of the present study. Sleep quality was self-assessed using the Pittsburgh Sleep Quality Index (PSQI). The HS volumes were measured using sub-millimetre in-plane resolution T2-weighted magnetic resonance imaging data. A total of 67 cognitively normal elderly individuals aged 60-83 years were classified into 30 normal sleepers with a PSQI <5 and 37 poor sleepers with a PSQI ≥5. The two groups were equivalent in age, gender distribution, ethnicity, education attainment, handedness and cognitive performance. Compared to normal sleepers, poor sleepers exhibited significantly lower normalised volumes in the left cornu ammonis field 1 (CA1), dentate gyrus (DG) and subiculum. In contrast, there were no significant differences in normalised grey and white matter volumes between the two groups. The global PSQI was negatively associated with the normalised volumes of the left CA1, DG and subiculum. Sleep duration was associated with the normalised volumes of the bilateral CA1, DG, left CA2 and subiculum. Verbal memory scores were associated with the left CA1 volume. In conclusion, poor sleep quality, especially insufficient sleep duration, was associated with volume loss in several HSs that are involved in specific learning and memory tasks. As the hippocampus does not regulate sleep, it is more likely that poor sleep leads to small hippocampi. Thus, based on this assumption, improving sleep quality of poor sleeper elderly individuals could benefit hippocampal health.

Diastolic Blood Pressure Is Associated With Regional White Matter Lesion Load: The Northern Manhattan Study.

Background and Purpose- Few studies have examined the separate contributions of systolic blood pressure and diastolic blood pressures (DBP) on subclinical cerebrovascular disease, especially using the 2017 American College of Cardiology/American Heart Association Blood Pressure Guidelines. Furthermore, associations with region-specific white matter hyperintensity volume (WMHV) are underexplored. Methods- Using data from the NOMAS (Northern Manhattan Study), a prospective cohort study of stroke risk and cognitive aging, we examined associations between systolic blood pressure and DBP, defined by the 2017 American College of Cardiology/American Heart Association guidelines, with regional WMHV. We used a linear mixed model approach to account for the correlated nature of regional brain measures. Results- The analytic sample (N=1205; mean age 64±8 years) consisted of 61% women and 66% Hispanics/Latinos. DBP levels were significantly related to WMHV differentially across regions (P for interaction<0.05). Relative to those with DBP 90+ mm Hg, participants with DBP <80 mm Hg had 13% lower WMHV in the frontal lobe (95% CI, -21% to -3%), 11% lower WMHV in the parietal lobe (95% CI, -19% to -1%), 22% lower WMHV in the anterior periventricular region (95% CI, -30% to -14%), and 16% lower WMHV in the posterior periventricular region (95% CI, -24% to -6%). Participants with DBP 80 to 89 mm Hg also exhibited about 12% (95% CI, -20% to -3%) lower WMHV in the anterior periventricular region and 9% (95% CI, -18% to -0.4%) lower WMHV in the posterior periventricular region, relative to participants with DBP 90≥ mm Hg. Post hoc pairwise t tests showed that estimates for periventricular WMHV were significantly different from estimates for temporal WMHV (Holms stepdown-adjusted P<0.05). Systolic blood pressure was not strongly related to regional WMHV. Conclusions- Lower DBP levels, defined by the 2017 American College of Cardiology/American Heart Association guidelines, were related to lower white matter lesion load, especially in the periventricular regions relative to the temporal region.

Comparing invasive with MRI-derived intracranial pressure measurements in healthy elderly and brain trauma cases: A pilot study.

BACKGROUND: Intracranial pressure (ICP) is an important physiological parameter in several neurological disorders. Considerable effort has been made to measure ICP noninvasively. MR-based ICP (MR-ICP) is a nonempirical method based on principles of cerebrospinal fluid (CSF) physiology, where ICP is obtained from measurements of blood and CSF flows to and from the cranium during the cardiac cycle. PURPOSE: To compare MR-ICP with invasive ICP measurements obtained using lumbar puncture (LP) or external ventricular drainage (EVD). STUDY TYPE: Prospective, cross-sectional, observational study. SUBJECTS: Ten cognitively healthy elderly subjects (age 69.6 ± 6.6 years; seven females) and six brain trauma patients (age 36.8 ± 19.7 years; two females). FIELD STRENGTH: Velocity encoding cine phase-contrast at 1.5 T and 3 T. ASSESSMENT: MR-ICP and craniospinal compliance distribution were estimated from arterial inflow and venous outflow to and from cranium, and craniospinal CSF flow at the upper cervical region, measured using cine phase contrast MRI. LP (done 177 ± 163 days after scan) and EVD measurements (at the time of scan) were performed in lateral recumbent and supine positions, respectively. STATISTICAL TESTS: Linear regression was used to assess the relationships of MR-ICP with invasive ICP, and the dependency of these measurements on age, weight, height, and BMI. A Shapiro-Wilks test and Bland-Altman plot were respectively used to evaluate the normality and agreement between these two pressure distributions. Student's t-test was used throughout the analysis to compare differences between the EVD and LP cohorts. RESULTS: In the combined cohort, MR-ICP and invasive ICP were positively correlated (r = 0.95, P < 0.001), with invasive ICP being higher than MR-ICP by 2.2 mmHg on average. In the healthy cohort, the cranial contribution to total craniospinal compliance was negatively correlated with MR-ICP (r = -0.90, P < 0.001). DATA CONCLUSION: MR-ICP provides a reliable estimate of ICP, with 14 out of 16 datapoints within the clinically acceptable error. Craniospinal compliance distribution plays a role in modulating ICP in supine position. LEVEL OF EVIDENCE: 3 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;50:975-981.

MRI-based assessment of acute effect of head-down tilt position on intracranial hemodynamics and hydrodynamics.

PURPOSE: To quantify the acute effect of the head-down tilt (HDT) posture on intracranial hemodynamics and hydrodynamics. MATERIALS AND METHODS: We evaluated the intracranial physiological parameters, blood flow-related parameters, and brain morphology in the HDT (-6° and -12°) and the horizontal supine (HS) positions. Seven and 15 healthy subjects were scanned for each position using 3.0 T magnetic resonance imaging system. The peak-to-peak intracranial volume change, the peak-to-peak cerebrospinal fluid (CSF) pressure gradient (PGp-p ), and the intracranial compliance index were calculated from the blood and CSF flow determined using a cine phase-contrast technique. The brain volumetry was conducted using SPM12. The measurements were compared using the Wilcoxon signed-rank test or a paired t-test. RESULTS: No measurements changed in the -6° HDT. The PGp-p and venous outflow of the internal jugular veins (IJVs) in the -12° HDT were significantly increased compared to the HS (P < 0.001 and P = 0.025, respectively). The cross-sectional areas of the IJVs were significantly larger (P < 0.001), and the maximum, minimum, and mean blood flow velocity of the IJVs were significantly decreased (P = 0.003, < 0.001, and = 0.001, respectively) in the -12° HDT. The mean blood flow velocities of the internal carotid arteries were decreased (P = 0.023). Neither position affected the brain volume. CONCLUSION: Pressure gradient and venous outflow were increased in accordance with the elevation of the intracranial pressure as an acute effect of the HDT. However, the CSF was not constantly shifted from the spinal canal to the cranium. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2018;47:565-571.

Regional Subclinical Cerebrovascular Disease Is Associated with Balance in an Elderly Multi-Ethnic Population.

INTRODUCTION: White matter hyperintensity volume (WMHV) and subclinical brain infarcts (SBI) are associated with impaired mobility, but less is known about the association of WMHV in specific brain regions. We hypothesized that anterior WMHV would be associated with lower scores on the Short Physical Performance Battery (SPPB), a well-validated mobility scale. METHODS: The SPPB was measured a median of 5 years after enrollment into the Northern Manhattan MRI sub study. Volumetric distributions for WMHV in 14 brain regions as a proportion of total cranial volume were determined. Multi-variable linear regression was performed to examine the association of SBI and regional log-WMHV with the SPPB score. RESULTS: Among 668 participants with SPPB measurements (mean 74 ± 9 years, 37% male and 70% Hispanic), the mean SPPB score was 8.2 ± 2.9. Total (beta = -0.3 per SD, p = 0.001), anterior periventricular (beta = -0.4 per SD, p = 0.001), parietal (beta = -0.2 per SD, p = 0.02) and frontal (beta = -0.3 per SD, p = 0.002) WMHVs were associated with SPPB; other WMHV and SBI were not associated with the SPPB. CONCLUSIONS: WMHV, especially in the anterior -cerebral regions, is associated with a lower SPPB. Prevention of subclinical cerebrovascular disease is a potential target to prevent physical decline in the elderly.

Brain Arterial Diameters and Cognitive Performance: The Northern Manhattan Study.

OBJECTIVES: To test the hypothesis that brain arterial diameters are associated with cognitive performance, particularly in arteries supplying domain-specific territories. METHODS: Stroke-free participants in the Northern Manhattan Study were invited to have a brain MRI from 2003-2008. The luminal diameters of 13 intracranial arterial segments were obtained using time-of-flight magnetic resonance angiogram (MRA), and then averaged and normalized into a global score and region-specific arterial diameters. Z-Scores for executive function, semantic memory, episodic memory and processing speed were obtained at MRI and during follow-up. Adjusted generalized additive models were used to assess for associations. RESULTS: Among the 1034 participants with neurocognitive testing and brain MRI, there were non-linear relationships between left anterior (ACA) and middle cerebral artery (MCA) diameter and semantic memory Z-scores (χ2=10.00; DF=3; p=.019), and left posterior cerebral artery (PCA) and posterior communicating artery (Pcomm) mean diameter and episodic memory Z-scores (χ2=9.88; DF=3; p=.020). Among the 745 participants who returned for 2nd neuropsychological testing, on average 5.0±0.4 years after their MRI, semantic memory change was associated non-linearly with the left PCA/Pcomm mean diameter (χ2=13.09; DF=3; p=.004) and with the right MCA/ACA mean diameter (χ2=8.43; DF=3; p=.03). In both cross-sectional and longitudinal analyses, participants with the larger brain arterial diameters had more consistently lower Z-scores and greater decline than the rest of the participants. CONCLUSIONS: Brain arterial diameters may have downstream effects in brain function presenting as poorer cognition. Identifying the mechanisms and the directionality of such interactions may increase the understanding of the vascular contribution to cognitive impairment and dementia. (JINS, 2018, 24, 335-346).

Spaceflight-Induced Visual Impairment and Globe Deformations in Astronauts Are Linked to Orbital Cerebrospinal Fluid Volume Increase.

OBJECTIVE: Most of the astronauts onboard the International Space Station (ISS) develop visual impairment and ocular structural changes that are not fully reversible upon return to earth. Current understanding assumes that the so-called visual impairments/intracranial pressure (VIIP) syndrome is caused by cephalad vascular fluid shift. This study assesses the roles of cerebrospinal fluid (CSF) and intracranial pressure (ICP) in VIIP. MATERIALS AND METHODS: Seventeen astronauts, 9 who flew a short-duration mission on the space shuttle (14.1 days [SD 1.6]) and 7 who flew a long-duration mission on the ISS (188 days [SD 22]) underwent MRI of the brain and orbits to assess the pre-to-post spaceflight changes in four categories: VIIP severity measures: globe flattening and nerve protrusion; orbital and ventricular CSF volumes; cortical gray and white matter volumes; and MR-derived ICP (MRICP). RESULTS: Significant pre-to-post-flight increase in globe flattening and optic nerve protrusion occurred only in the long-duration cohort (0.031 [SD 0.019] vs -0.001 [SD 0.006], and 0.025 [SD 0.013] vs 0.001 [SD 0.006]; p < 0.00002 respectively). The increased globe deformations were associated with significant increases in orbital and ventricular CSF volumes, but not with increased tissue vascular fluid content. Additionally, a moderate increase in MRICP of 6 mmHg was observed in only two ISS astronauts with large ocular structure changes. CONCLUSIONS: These findings are evidence for the primary role of CSF and a lesser role for intracranial cephalad fluid-shift in the formation of VIIP. VIIP is caused by a prolonged increase in orbital CSF spaces that compress the globes' posterior pole, even without a large increase in ICP.

Systemic Atherosclerosis Relate to Brain Arterial Diameters: The Northern Manhattan Study.

BACKGROUND: Phenotypic expressions of arterial disease vary throughout the body and it is not clear to what extent systemic atherosclerosis influences brain arterial remodeling. We aim to test the hypothesis that systemic atherosclerosis is associated with brain arterial diameters. METHODS: Stroke-free participants in the Northern Manhattan Study MRI subcohort in whom carotid ultrasound, transthoracic echocardiogram, and brain MRA (n = 482) were performed were included in this analysis. Brain arterial diameters were measured with semi-automated software as continuous and categorical variables. Ultrasound and echocardiography provided the sum of maximum carotid plaque thickness (sMCPT) and aortic plaque thickness. Associations between brain arterial diameters and aortic and carotid plaque thickness were assessed with semi-parametric generalized additive models. RESULTS: Aortic plaque thickness was inversely and linearly associated with brain arterial diameters (B per mm = -0.073 ± 0.034, p = 0.03), while sMCPT was associated nonlinearly in a u-shaped curve with anterior brain arterial diameters (spline regression χ2 = 9.19, p = 0.02). Coexisting carotid and aortic atherosclerosis were more prevalent in participants with small luminal diameters (40%) compared with participants with average (30%) or with large (13%) luminal diameters, while carotid atherosclerosis without aortic atherosclerosis was more prevalent among participants with large luminal diameters (31%) compared with those with average (12%) or small luminal diameters (2%, p < 0.001 for both trends). CONCLUSIONS: We confirmed the hypothesis that systemic arterial disease is associated with brain arterial diameters. Gaining knowledge about the origin of these phenotypic expressions of atherosclerosis in the human body may lead to a better understanding of the cerebrovascular consequences of the systemic arterial disease.

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

OBJECTIVE: The study was undertaken to determine whether normobaric hypoxia causes elevated brain volume and intracranial pressure in individuals with symptoms consistent with acute mountain sickness (AMS). METHODS: Thirteen males age = (26 (sd 6)) years were exposed to normobaric hypoxia (12% O2 ) and normoxia (21% O2 ). After 2 and 10 hours, AMS symptoms were assessed alongside ventricular and venous vessel volumes, cerebral blood flow, regional brain volumes, and intracranial pressure, using high-resolution magnetic resonance imaging. RESULTS: In normoxia, neither lateral ventricular volume (R(2) = 0.07, p = 0.40) nor predominance of unilateral transverse venous sinus drainage (R(2) = 0.07, p = 0.45) was related to AMS symptoms. Furthermore, despite an increase in cerebral blood flow after 2 hours of hypoxia (hypoxia vs normoxia: Δ148ml/min(-1) , 95% confidence interval [CI] = 58 to 238), by 10 hours, when AMS symptoms had developed, cerebral blood flow was normal (Δ-51ml/min(-1) , 95% CI = -141 to 39). Conversely, at 10 hours brain volume was increased (Δ59ml, 95% CI = 8 to 110), predominantly due to an increase in gray matter volume (Δ73ml, 95% CI = 25 to 120). Therefore, cerebral spinal fluid volume was decreased (Δ-40ml, 95% CI = -67 to -14). The intracranial pressure response to hypoxia varied between individuals, and as hypothesized, the most AMS-symptomatic participants had the largest increases in intracranial pressure (AMS present, Δ7mmHg, 95% CI = -2.5 to 17.3; AMS not present, Δ-1mmHg, 95% CI = -3.3 to 0.5). Consequently, there was a significant relationship between the change in intracranial pressure and AMS symptom severity (R(2) = 0.71, p = 0.002). INTERPRETATION: The data provide the strongest evidence to date to support the hypothesis that the "random" nature of AMS symptomology is explained by a variable intracranial pressure response to hypoxia.

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

PURPOSE: To add the hydrostatic component of the cerebrospinal fluid (CSF) pressure to magnetic resonance imaging (MRI)-derived intracranial pressure (ICP) measurements in the upright posture for derivation of pressure value in a central cranial location often used in invasive ICP measurements. MATERIALS AND METHODS: Additional analyses were performed using data previously collected from 10 healthy subjects scanned in supine and sitting positions with a 0.5T vertical gap MRI scanner (GE Medical). Pulsatile blood and CSF flows to and from the brain were quantified using cine phase-contrast. Intracranial compliance and pressure were calculated using a previously described method. The vertical distance between the location of the CSF flow measurement and a central cranial location was measured manually in the mid-sagittal T1 -weighted image obtained in the upright posture. The hydrostatic pressure gradient of a CSF column with similar height was then added to the MR-ICP value. RESULTS: After adjustment for the hydrostatic component, the mean ICP value was reduced by 7.6 mmHg. Mean ICP referenced to the central cranial level was -3.4 ± 1.7 mmHg compared to the unadjusted value of +4.3 ± 1.8 mmHg. CONCLUSION: In the upright posture, the hydrostatic pressure component needs to be added to the MRI-derived ICP values for compatibility with invasive ICP at a central cranial location.

Diagnostic performance of CT attenuation values of focal 18F-FDG avid breast lesions detected on whole-body PET-CT in postoperative breast cancer patients.

To assess whether CT attenuation values help in differentiating benign from malignant etiology of focal (18) F-FDG avid breast lesions detected on whole-body PET/CT exam in postoperative breast cancer patients. Institutional review board approval and waived informed consent were obtained for this HIPAA-compliant retrospective study. Between January 2009 and July 2011, a total of 85 patients had 97 focal (18) F-FDG avid breast lesions on whole-body PET/CT. Of these, 54 (56%) lesions were biopsy-proven primary invasive breast carcinoma that had not undergone treatment at the time of PET/CT, 35 (36%) were benign lesions, and 8 were locally recurrent breast carcinoma. Mean attenuation values were retrospectively measured in Hounsfield units (HU) for the correlative lesion on the CT portion of the exam. Receiver-operating characteristic curves (ROC) were calculated to determine the optimal cutoff values of HU that would best discriminate between benign and malignant lesions. Interobserver agreement for measured mean attenuation values was assessed by calculating the intraclass correlation coefficient (ICC). Mean HU for the benign lesions group and the local recurrence lesions group was -11.0 ± 30.3 versus 32.9 ± 6.87 (p < 0.0002). ROC curve analysis comparing benign breast lesions to local recurrence lesions found an optimal cutoff value of 17 HU (area under curve = 0.982, p < 0.0001, Sensitivity = 100%, Specificity = 89%). ICC with regard to interobserver agreement in measuring the mean HU of the benign lesions was 0.84 (95% confidence interval 0.64-0.93) and for the malignant lesions was 0.88 (95% confidence interval 0.77-0.94). A CT attenuation threshold value of less than 17 HU suggests benign etiology of focal (18) FDG avid breast lesions in postoperative breast cancer patients. If confirmed by additional studies, these findings may provide additional information to guide the treating physician regarding decisions for supplementary imaging or the need to biopsy.

Inter- and intra-rater reliability of blood and cerebrospinal fluid flow quantification by phase-contrast MRI.

PURPOSE: To evaluate the intra- and inter-rater reliability of the quantification of blood and CSF flow rates by phase contrast MRI. MATERIALS AND METHODS: Blood and CSF flows in the upper cervical region were imaged with velocity-encoded cine-phase contrast using 3T scanners from different manufacturers at two centers. Data of 6 subjects scanned in center A and of 5 subjects in center B were analyzed by six readers at two levels of training. Each data set was analyzed three times in a randomized order for a total of 33 data sets. Intra-class correlation coefficients (ICC) were calculated for the primary measurements of areas and flow rates through the main cervical arteries, veins and the CSF space, and for secondary parameters derived from the individual flow rates. RESULTS: ICC ranged from 0.80 to 0.96 for the lumen area and from 0.97 to 0.99 for the volumetric flow rate. The ICC for the derived secondary measures ranged from 0.85 to 0.99. Differences due to operator level of training were not statistically significant. CONCLUSION: High intra- and inter-rater reliability of volumetric flow rate measurements is currently achievable across manufacturers and users' skill levels with a pulsatility based automated lumen segmentation.

Circle of Willis configuration as a determinant of intracranial dolichoectasia.

BACKGROUND: Circle of Willis (COW) variants might influence arterial caliber in the brain. We hypothesized that these variants would be associated with the prevalence of intracranial dolichoectasia (DE). METHODS: We examined COW variants and DE in a sample of stroke-free participants (n = 436) undergoing magnetic resonance angiography (MRA) as part of a population-based study. Large intracranial arterial diameters were obtained when available; if not, the artery was defined as hypoplastic or absent according to its visibility on MRA. Subscores for the anterior and the posterior circulations were created. DE was defined as arterial diameters ≥2 SD above the population mean for that artery, adjusting for intracranial volume. Generalized linear models with a Poisson distribution were used to evaluate predictors of both absent and hypoplastic vessels, and logistic regression was used to assess the odds ratio (OR) and 95% confidence interval (95% CI) of DE depending on COW variants. RESULTS: Only 44% of the sample had all 14 arteries present, 32% lacked 1 artery, 18% lacked 2 and 6% lacked 3 or more. DE of at least 1 artery was not associated with the total number of hypoplastic or absent arteries, but DE in a posterior circulation artery was weakly associated with the number of absent arteries in the posterior circulation (ß coefficient = 0.36, p = 0.06). DE of at least 1 artery was more frequent in those with 1 or more absent arteries (OR 1.27, 95% CI 1.03-1.57). Posterior circulation DE was more frequent in participants with at least 1 or more absent arteries at any location (OR 1.35, 95% CI 1.02-1.78). Participants with an incomplete posterior COW were more likely to have DE in the anterior circulation (OR 1.52, 95% CI 1.01-2.33). Having an absent left anterior cerebral artery (ACA) A1 segment was associated with right ACA DE (OR 34.1, 95% CI 3.16-368.2); an absent right ACA was associated with left ACA DE (OR 14.1, 95% CI 1.69-118.28). Absence of 1 (OR 1.9, 95% CI 1.1-3.4) or 2 (OR 3.0, 95% CI 1.4-6.6) of the 2 arteries connecting the anterior to the posterior circulation was associated with basilar artery DE. CONCLUSION: The COW is a pleomorphic structure that allows collateral flow to compensate for an insufficient or absent arterial component at the base of the skull. By presumed flow diversion, arteries might undergo outward remodeling. Whether this compensatory arterial dilatation is beneficial or not remains unknown.