In the evaluation of cerebrovascular CO2 reactivity measurements, it is often assumed that the diameter of the large intracranial arteries insonated by transcranial Doppler remains unaffected by ...changes in arterial CO2 partial pressure. However, the strong cerebral vasodilatory capacity of CO2 challenges this assumption, suggesting that there should be some changes in diameter, even if very small. Data from previous studies on effects of CO2 on cerebral artery diameter middle cerebral artery (MCA) have been inconsistent. In this study, we examined 10 healthy subjects (5 women, 5 men, age 21-30 yr). High-resolution (0.2 mm in-plane) MRI scans at 7 Tesla were used for direct observation of the MCA diameter during hypocapnia, -1 kPa (-7.5 mmHg), normocapnia, 0 kPa (0 mmHg), and two levels of hypercapnia, +1 and +2 kPa (7.5 and 15 mmHg), with respect to baseline. The vessel lumen was manually delineated by two independent observers. The results showed that the MCA diameter increased by 6.8 ± 2.9% in response to 2 kPa end-tidal P(CO2) (PET(CO2)) above baseline. However, no significant changes in diameter were observed at the -1 kPa (-1.2 ± 2.4%), and +1 kPa (+1.4 ± 3.2%) levels relative to normocapnia. The nonlinear response of the MCA diameter to CO2 was fitted as a continuous calibration curve. Cerebral blood flow changes measured by transcranial Doppler could be corrected by this calibration curve using concomitant PET(CO2) measurements. In conclusion, the MCA diameter remains constant during small deviations of the PET(CO2) from normocapnia, but increases at higher PET(CO2) values.
White matter hyperintensities are frequent on neuroimaging of older people and are a key feature of cerebral small vessel disease. They are commonly attributed to chronic hypoperfusion, although ...whether low cerebral blood flow is cause or effect is unclear. We systematically reviewed studies that assessed cerebral blood flow in small vessel disease patients, performed meta-analysis and sensitivity analysis of potential confounders. Thirty-eight studies (n = 4006) met the inclusion criteria, including four longitudinal and 34 cross-sectional studies. Most cerebral blood flow data were from grey matter. Twenty-four cross-sectional studies (n = 1161) were meta-analysed, showing that cerebral blood flow was lower in subjects with more white matter hyperintensity, globally and in most grey and white matter regions (e.g. mean global cerebral blood flow: standardised mean difference−0.71, 95% CI −1.12, −0.30). These cerebral blood flow differences were attenuated by excluding studies in dementia or that lacked age-matching. Four longitudinal studies (n = 1079) gave differing results, e.g., more baseline white matter hyperintensity predated falling cerebral blood flow (3.9 years, n = 575); cerebral blood flow was low in regions that developed white matter hyperintensity (1.5 years, n = 40). Cerebral blood flow is lower in subjects with more white matter hyperintensity cross-sectionally, but evidence for falling cerebral blood flow predating increasing white matter hyperintensity is conflicting. Future studies should be longitudinal, obtain more white matter data, use better age-correction and stratify by clinical diagnosis.
Purpose
Dynamic contrast‐enhanced (DCE) MRI can be used to measure blood‐brain barrier (BBB) leakage. In neurodegenerative disorders such as small vessel disease and dementia, the leakage can be very ...subtle and the corresponding signal can be rather noisy. For these reasons, an optimized DCE‐MRI measurement and study design is required. To this end, a new measure indicative of the spatial extent of leakage is introduced and the effects of scan time and sample size are explored.
Methods
Dual‐time resolution DCE‐MRI was performed in 16 patients with early Alzheimer's disease (AD) and 17 healthy controls. The leakage rate (Ki) and volume fraction of detectable leaking tissue (vL) to quantify the spatial extent of BBB leakage were calculated in cortical gray matter and white matter using noise‐corrected histogram analysis of leakage maps. Computer simulations utilizing realistic Ki histograms, mimicking the strong effect of noise and variation in Ki values, were performed to understand the influence of scan time on the estimated leakage.
Results
The mean Ki was very low (order of 10−4 min−1) and highly influenced by noise, causing the Ki to be increasingly overestimated at shorter scan times. In the white matter, the Ki was not different between patients with early AD and controls, but was higher in the cortex for patients, reaching significance after 14.5 min of scan time. To detect group differences, vL proved more suitable, showing significantly higher values for patients compared with controls in the cortex after 8 minutes of scan time, and in white matter after 15.5 min.
Conclusions
Several ways to improve the sensitivity of a DCE‐MRI experiment to subtle BBB leakage were presented. We have provided vL as an attractive and potentially more time‐efficient alternative to detect group differences in subtle and widespread blood‐brain barrier leakage compared with leakage rate Ki. Recommendations on group size and scan time are made based on statistical power calculations to aid future research.
Aortic stiffness increases with age and vascular risk factor exposure and is associated with increased risk for structural and functional abnormalities in the brain. High ambient flow and low ...impedance are thought to sensitize the cerebral microcirculation to harmful effects of excessive pressure and flow pulsatility. However, haemodynamic mechanisms contributing to structural brain lesions and cognitive impairment in the presence of high aortic stiffness remain unclear. We hypothesized that disproportionate stiffening of the proximal aorta as compared with the carotid arteries reduces wave reflection at this important interface and thereby facilitates transmission of excessive pulsatile energy into the cerebral microcirculation, leading to microvascular damage and impaired function. To assess this hypothesis, we evaluated carotid pressure and flow, carotid-femoral pulse wave velocity, brain magnetic resonance images and cognitive scores in participants in the community-based Age, Gene/Environment Susceptibility - Reykjavik study who had no history of stroke, transient ischaemic attack or dementia (n = 668, 378 females, 69-93 years of age). Aortic characteristic impedance was assessed in a random subset (n = 422) and the reflection coefficient at the aorta-carotid interface was computed. Carotid flow pulsatility index was negatively related to the aorta-carotid reflection coefficient (R = −0.66, P<0.001). Carotid pulse pressure, pulsatility index and carotid-femoral pulse wave velocity were each associated with increased risk for silent subcortical infarcts (hazard ratios of 1.62-1.71 per standard deviation, P<0.002). Carotid-femoral pulse wave velocity was associated with higher white matter hyperintensity volume (0.108 ± 0.045 SD/SD, P = 0.018). Pulsatility index was associated with lower whole brain (−0.127 ± 0.037 SD/SD, P<0.001), grey matter (−0.079 ± 0.038 SD/SD, P = 0.038) and white matter (−0.128 ± 0.039 SD/SD, P<0.001) volumes. Carotid-femoral pulse wave velocity (−0.095 ± 0.043 SD/SD, P = 0.028) and carotid pulse pressure (−0.114 ± 0.045 SD/SD, P = 0.013) were associated with lower memory scores. Pulsatility index was associated with lower memory scores (−0.165 ± 0.039 SD/SD, P<0.001), slower processing speed (−0.118 ± 0.033 SD/SD, P<0.001) and worse performance on tests assessing executive function (−0.155 ± 0.041 SD/SD, P<0.001). When magnetic resonance imaging measures (grey and white matter volumes, white matter hyperintensity volumes and prevalent subcortical infarcts) were included in cognitive models, haemodynamic associations were attenuated or no longer significant, consistent with the hypothesis that increased aortic stiffness and excessive flow pulsatility damage the microcirculation, leading to quantifiable tissue damage and reduced cognitive performance. Marked stiffening of the aorta is associated with reduced wave reflection at the interface between carotid and aorta, transmission of excessive flow pulsatility into the brain, microvascular structural brain damage and lower scores in various cognitive domains.
The study of brain clearance mechanisms is an active area of research. While we know that the cerebrospinal fluid (CSF) plays a central role in one of the main existing clearance pathways, the exact ...processes for the secretion of CSF and the removal of waste products from tissue are under debate. CSF is thought to be created by the exchange of water and ions from the blood, which is believed to mainly occur in the choroid plexus. This exchange has not been thoroughly studied in vivo.
We propose a modified arterial spin labeling (ASL) MRI sequence and image analysis to track blood water as it is transported to the CSF, and to characterize its exchange from blood to CSF. We acquired six pseudo-continuous ASL sequences with varying labeling duration (LD) and post-labeling delay (PLD) and a segmented 3D-GRASE readout with a long echo train (8 echo times (TE)) which allowed separation of the very long-T2 CSF signal. ASL signal was observed at long TEs (793 ms and higher), indicating presence of labeled water transported from blood to CSF. This signal appeared both in the CSF proximal to the choroid plexus and in the subarachnoid space surrounding the cortex. ASL signal was separated into its blood, gray matter and CSF components by fitting a triexponential function with T2s taken from literature. A two-compartment dynamic model was introduced to describe the exchange of water through time and TE. From this, a water exchange time from the blood to the CSF (Tbl->CSF) was mapped, with an order of magnitude of approximately 60 s.
Objectives
To evaluate the association between various blood pressure (BP) measures at age 85 and future decline in physical and cognitive function the oldest old.
Design
Longitudinal study.
Setting
...The population‐based Leiden 85‐plus Study.
Participants
Five hundred seventy‐two 85‐year‐old community‐dwelling individuals.
Measurements
BP was measured at age 85 during home visits. Activities of daily living (ADLs) and Mini‐Mental State Examination (MMSE) were assessed at age 85 and annually thereafter up to age 90. On average, participants were followed for 3.2 years. Cross‐sectional and longitudinal analyses were performed using linear regression models using systolic BP (SBP), diastolic BP (DBP), mean arterial pressure (MAP), and pulse pressure (PP) as the determinants. All analyses were adjusted for sociodemographic and cardiovascular factors.
Results
At age 85, higher SBP and PP were associated with lower ADL disability scores (both P = .01). Similarly, higher SBP, DBP, and MAP were associated with higher MMSE scores (all P < .05). From age 85 onward, higher SBP (P < .001), MAP (P = .01), and PP (P = .003) at age 85 were associated with lower annual increases in ADL disability scores. Likewise, higher SBP (P = .03) and PP (P = .008) at age 85 were associated with lower annual declines in MMSE scores. Additional analyses showed that the association between high BP and lower annual decline in MMSE score was most pronounced in participants with high ADL disability.
Conclusion
In the oldest old, higher SBP and PP are associated with resilience to physical and cognitive decline, especially in individuals with pre‐existing physical disability.
Purpose To investigate whether the blood-brain barrier (BBB) leaks blood-circulating substances in patients with early forms of Alzheimer disease (AD), and if so, to examine the extent and pattern of ...leakage. Materials and Methods This study was approved by the local medical ethical committees of the Maastricht University Medical Center and Leiden University Medical Center, and written informed consent was obtained from all subjects. For this pilot study, 16 patients with early AD and 17 healthy age-matched control subjects underwent dynamic contrast material-enhanced magnetic resonance (MR) imaging sequence with dual time resolution for 25 minutes. The Patlak graphical approach was used to quantify the BBB leakage rate and local blood plasma volume. Subsequent histogram analysis was used to determine the volume fraction of the leaking brain tissue. Differences were assessed with linear regression analysis, adjusted for confounding variables. Results The BBB leakage rate was significantly higher in patients compared with that in control subjects in the total gray matter (P < .05) and cortex (P = .03). Patients had a significantly higher volume fraction of the leaking brain tissue in the gray matter (P = .004), normal-appearing white matter (P < .04), deep gray matter (P = .01), and cortex (P = .004). When all subjects were considered, scores on the Mini-Mental State Examination decreased significantly with increasing leakage in the deep gray matter (P = .007) and cortex (P < .05). Conclusion The results of this study showed global BBB leakage in patients with early AD that is associated with cognitive decline. A compromised BBB may be part of a cascade of pathologic events that eventually lead to cognitive decline and dementia.
RSNA, 2016 Online supplemental material is available for this article.
INTRODUCTION
We aimed to investigate the association between white matter hyperintensity (WMH) shape and volume and the long‐term dementia risk in community‐dwelling older adults.
METHODS
Three ...thousand seventy‐seven participants (mean age: 75.6 ± 5.2 years) of the Age Gene/Environment Susceptibility (AGES)‐Reykjavik study underwent baseline 1.5T brain magnetic resonance imaging and were followed up for dementia (mean follow‐up: 9.9 ± 2.6 years).
RESULTS
More irregular shape of periventricular/confluent WMH (lower solidity (hazard ratio (95% confidence interval) 1.34 (1.17 to 1.52), p < .001) and convexity 1.38 (1.28 to 1.49), p < .001); higher concavity index 1.43 (1.32 to 1.54), p < .001) and fractal dimension 1.45 (1.32 to 1.58), p < .001)), higher total WMH volume (1.68 (1.54 to 1.87), p < .001), higher periventricular/confluent WMH volume (1.71 (1.55 to 1.89), p < .001), and higher deep WMH volume (1.17 (1.08 to 1.27), p < .001) were associated with an increased long‐term dementia risk.
DISCUSSION
WMH shape markers may in the future be useful in determining patient prognosis and may aid in patient selection for future preventive treatments in community‐dwelling older adults.
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