Anesthesia Depresses Cerebrovascular Reactivity to Acetazolamide in Pediatric Moyamoya Vasculopathy

Measurements of cerebrovascular reactivity (CVR) are essential for treatment decisions in moyamoya vasculopathy (MMV). Since MMV patients are often young or cognitively impaired, anesthesia is commonly used to limit motion artifacts. Our aim was to investigate the effect of anesthesia on the CVR in pediatric MMV. We compared the CVR with multidelay-ASL and BOLD MRI, using acetazolamide as a vascular stimulus, in all awake and anesthesia pediatric MMV scans at our institution. Since a heterogeneity in disease and treatment influences the CVR, we focused on the (unaffected) cerebellum. Ten awake and nine anesthetized patients were included. The post-acetazolamide CBF and ASL-CVR were significantly lower in anesthesia patients (47.1 ± 15.4 vs. 61.4 ± 12.1, p = 0.04; 12.3 ± 8.4 vs. 23.7 ± 12.2 mL/100 g/min, p = 0.03, respectively). The final BOLD-CVR increase (0.39 ± 0.58 vs. 3.6 ± 1.2% BOLD-change (mean/SD), p < 0.0001), maximum slope of increase (0.0050 ± 0.0040%/s vs. 0.017 ± 0.0059%, p < 0.0001), and time to maximum BOLD-increase (~463 ± 136 and ~697 ± 144 s, p = 0.0028) were all significantly lower in the anesthesia group. We conclude that the response to acetazolamide is distinctively different between awake and anesthetized MMV patients, and we hypothesize that these findings can also apply to other diseases and methods of measuring CVR under anesthesia. Considering that treatment decisions heavily depend on CVR status, caution is warranted when assessing CVR under anesthesia

Cognitive functions in children and adults with Moyamoya Vasculopathy: A systematic review and meta-analysis

Background and Purpose Patients with moyamoya vasculopathy (MMV) may experience cognitive impairment, but its reported frequency, severity, and nature vary. In a systematic review and meta-analysis, we aimed to assess the presence, severity, and nature of cognitive impairments in children and adults with MMV. Methods We followed the MOOSE guidelines for meta-analysis and systematic reviews of observational studies. We searched Ovid Medline and Embase for studies published between January 1, 1969 and October 4, 2016. Independent reviewers extracted data for mean intelligence quotient (IQ) and standardized z-scores for cognitive tests, and determined percentages of children and adults with cognitive deficits, before and after conservative or surgical treatment. We explored associations between summary measures of study characteristics and cognitive impairments by linear regression analysis. Results We included 17 studies (11 studies reporting on 281 children, six on 153 adults). In children, the median percentage with impaired cognition was 30% (range, 13% to 67%); median IQ was 98 (range, 71 to 107). Median z-score was –0.39 for memory, and –0.43 for processing speed. In adults, the median percentage with impaired cognition was 31% (range, 0% to 69%); median IQ was 95 (range, 94 to 99). Median z-scores of cognitive domains were between –0.9 and –0.4, with multiple domains being affected. We could not identify determinants of cognitive impairment. Conclusions A large proportion of children and adults with MMV have cognitive impairment, with modest to large deficits across various cognitive domains. Further studies should investigate determinants of cognitive deficits and deterioration, and the influence of revascularization treatment on cognitive functioning

The effect of amyloid pathology and glucose metabolism on cortical volume loss over time in Alzheimer’s disease

Purpose: The present multimodal neuroimaging study examined whether amyloid pathology and glucose metabolism are related to cortical volume loss over time in Alzheimer’s disease (AD) patients and healthy elderly controls. Methods: Structural MRI scans of eleven AD patients and ten controls were available at baseline and follow-up (mean interval 2.5 years). Change in brain structure over time was defined as percent change of cortical volume within seven a-priori defined regions that typically show the strongest structural loss in AD. In addition, two PET scans were performed at baseline: [[superscript 11]C]PIB to assess amyloid-β plaque load and [[superscript 18]F]FDG to assess glucose metabolism. [[superscript 11]C]PIB binding and [[superscript 18]F]FDG uptake were measured in the precuneus, a region in which both amyloid deposition and glucose hypometabolism occur early in the course of AD. Results: While amyloid-β plaque load at baseline was not related to cortical volume loss over time in either group, glucose metabolism within the group of AD patients was significantly related to volume loss over time (rho=0.56, p<0.05). Conclusion:The present study shows that in a group of AD patients amyloid-β plaque load as measured by [[superscript 11]C]PIB behaves as a trait marker (i.e., all AD patients showed elevated levels of amyloid, not related to subsequent disease course), whilst hypometabolism as measured by [[superscript 18]F]FDG changed over time indicating that it could serve as a state marker that is predictive of neurodegeneration.Hersenstichting Nederland (KS2011(1)-24)Athinoula A. Martinos Center for Biomedical ImagingInternationale Stichting Alzheimer Onderzoek (Project Number 11539

Novel application of postmortem CT angiography for evaluation of the intracranial vascular anatomy in cadaver heads

OBJECTIVE. Postmortem CT angiography is a common procedure used to visualize the entire human vasculature. For visualization of a specific organ's vascular anatomy, casting is the preferred method. Because of the permanent and damaging nature of casting, the organ cannot be further used as an experimental model after angiography. Therefore, there is a need for a minimally traumatic method to visualize organ-specific vascular anatomy. The purpose of this study was to develop and evaluate a contrast enhancement technique that is capable of visualizing the intracranial vascular anatomy while preserving the anatomic integrity in cadaver heads. MATERIALS AND METHODS. Seven human heads were used in this study. Heads were prepared by cannulating the vertebral and internal carotid arteries. Contrast agent was injected as a mixture of tap water, polyethylene glycol 600, and an iodinated contrast agent. Postmortem imaging was executed on a 64-MDCT scanner. Primary image review and 3D reconstruction were performed on a CT workstation. RESULTS. Clear visualization of the major cerebral arteries and smaller intracranial branches was achieved. Adequate visualization was obtained for both the anterior and posterior intracranial circulation. The minimally traumatic angiography method preserved the vascular integrity of the cadaver heads. CONCLUSION. A novel application of postmortem CT angiography is presented here. The technique can be used for radiologic evaluation of the intracranial circulation in cadaver heads. After CT angiography, the specimen can be used for further experimental or laboratory testing and teaching purposes

Effects of dobutamine and phenylephrine on cerebral perfusion in patients undergoing cerebral bypass surgery: a randomised crossover trial

BACKGROUND Patients undergoing cerebral bypass surgery are prone to cerebral hypoperfusion. Currently, arterial blood pressure is often increased with vasopressors to prevent cerebral ischaemia. However, this might cause vasoconstriction of the graft and cerebral vasculature and decrease perfusion. We hypothesised that cardiac output, rather than arterial blood pressure, is essential for adequate perfusion and aimed to determine whether dobutamine administration resulted in greater graft perfusion than phenylephrine administration. METHODS This randomised crossover study included 10 adult patients undergoing cerebral bypass surgery. Intraoperatively, patients randomly and sequentially received dobutamine to increase cardiac index or phenylephrine to increase mean arterial pressure (MAP). An increase of >10% in cardiac index or >10% in MAP was targeted, respectively. Before both interventions, a reference phase was implemented. The primary outcome was the absolute difference in graft flow between the reference and intervention phase. We compared the absolute flow difference between each intervention and constructed a random-effect linear regression model to explore treatment and carry-over effects. RESULTS Graft flow increased with a median of 4.1 (inter-quartile range [IQR], 1.7-12.0] ml min$^{-1}$) after dobutamine administration and 3.6 [IQR, 1.3-7.8] ml min$^{-1}$ after phenylephrine administration (difference -0.6 ml min$^{-1}$; 95% confidence interval [CI], -14.5 to 5.3; P=0.441). There was no treatment effect (0.9 ml min$^{-1}$; 95% CI, 0.0-20.1; P=0.944) and no carry-over effect. CONCLUSIONS Both dobutamine and phenylephrine increased graft flow during cerebral bypass surgery, without a preference for one method over the other. CLINICAL TRIAL REGISTRATION Netherlands Trial Register, NL7077 (https://www.trialregister.nl/trial/7077)

Vessel wall perforation mechanism of the excimer laser-assisted non-occlusive anastomosis technique

The excimer laser assisted non-occlusive anastomosis (ELANA) technique is used to make anastomoses on intracerebral arteries. This end-to-side anastomosis is created without temporary occlusion of the recipient artery using a 308-nm excimer laser with a ring-shaped multi-fiber catheter to punch an opening in the arterial wall. Over 500 patients have received an ELANA bypass. However, the vessel wall perforation mechanism of the laser catheter is not known exactly and not 100 % successful. In this study, we aimed to understand the mechanism of ELANA vessel perforation using specialized imaging techniques to ultimately improve its effectiveness. High-speed imaging, high-contrast imaging, and high-sensitivity thermal imaging were used to study the laser wall perforation mechanism and reveal the mechanical and thermal effects involved. In vitro, rabbit arteries were exposed with the special designed laser catheter in a setup representative for the clinical setting, in which blood was replaced with a transparent UV absorbing liquid for visualization. We observed that laser vessel wall perforation was caused by explosive vapor bubbles tearing through the vessel wall, mostly within the first 20 of the total 200 pulses. Thermal effects were minimal. Unsymmetrical tension in the vessel wall inducing migration of the flap during laser exposure was observed in case of unsuccessful wall perforations. The laser wall perforation mechanism in the ELANA technique is primarily mechanical. Symmetric tension in the recipient vessel wall is essential and should be trained by neurosurgeons

High resolution 7T and 9.4T-MRI of human cerebral arterial casts enables accurate estimations of the cerebrovascular morphometry

Quantitative data on the morphology of the cerebral arterial tree could aid in modelling and understanding cerebrovascular diseases, but is scarce in the range between 200 micrometres and 1 mm diameter arteries. Traditional manual measurements are difficult and time consuming. 7T-MRI and 9.4T-MRI of human cerebral arterial plastic casts could proof feasible for acquiring detailed morphological data of the cerebral arterial tree in a time efficient method. One cast of the complete human cerebral arterial circulation embedded in gadolinium-containing gelatine gel was scanned at 7T-MRI (0.1 mm isotropic resolution). A small section of another cast was scanned at 9.4T-MRI (30 µm isotropic resolution). Subsequent 3D-reconstruction was performed using a semi-automatic approach. Validation of 7T-MRI was performed by comparing the radius calculated using MRI to manual measurements on the same cast. As manual measurement of the small section was not feasible, 9.4T-MRI was validated by scanning the small section both at 7T-MRI and 9.4T MRI and comparing the diameters of arterial segments. Linear regression slopes were 0.97 (R-squared 0.94) and 1.0 (R-squared 0.90) for 7T-MRI and 9.4T-MRI. This data shows that 7T-MRI and 9.4T-MRI and subsequent 3D reconstruction of plastic casts is feasible, and allows for characterization of human cerebral arterial tree morphology