Blood oxygenation level-dependent (BOLD) or arterial spin labeling (ASL) MRI with hypercapnic stimuli allow for measuring cerebrovascular reactivity (CVR). Hypercapnic stimuli are also employed in calibrated BOLD functional MRI for quantifying neuronally-evoked changes in cerebral oxygen metabolism (CMRO₂). It is often assumed that hypercapnic stimuli (with or without hyperoxia) are iso-metabolic; increasing arterial CO₂ or O₂ does not affect CMRO₂. We evaluated the null hypothesis that two common hypercapnic stimuli, ‘CO₂ in air’ and carbogen, are iso-metabolic. TRUST and ASL MRI were used to measure the cerebral venous oxygenation and cerebral blood flow (CBF), from which the oxygen extraction fraction (OEF) and CMRO₂ were calculated for room-air, ‘CO₂ in air’ and carbogen. As expected, CBF significantly increased (9.9% ± 9.3% and 12.1% ± 8.8% for ‘CO₂ in air’ and carbogen, respectively). CMRO₂ decreased for ‘CO₂ in air’ (−13.4% ± 13.0%, p < 0.01) compared to room-air, while the CMRO₂ during carbogen did not significantly change. Our findings indicate that ‘CO₂ in air’ is not iso-metabolic, while carbogen appears to elicit a mixed effect; the CMRO₂ reduction during hypercapnia is mitigated when including hyperoxia. These findings can be important for interpreting measurements using hypercapnic or hypercapnic-hyperoxic (carbogen) stimuli.

Background: It remains unclear whether revascularization of moyamoya vasculopathy (MMV) has a positive effect on cognitive function. In this prospective, single-center study, we investigated the effect of revascularization on cognitive function in patients with MMV. We report clinical and radiological outcome parameters and the associations between clinical determinants and change in neurocognitive functioning. Methods: We consecutively included all MMV patients at a Dutch tertiary referral hospital who underwent pre- and postoperative standardized neuropsychological evaluation, [¹⁵O]H₂O-PET (including cerebrovascular reactivity (CVR)), MRI, cerebral angiography, and completed standardized questionnaires on clinical outcome and quality of life (QOL). To explore the association between patient characteristics, imaging findings, and change in the z-scores of the cognitive domains, we used multivariable linear- and Bayesian regression analysis. Results: We included 40 patients of whom 35 (27 females, 21 children) were treated surgically. One patient died after surgery, and two withdrew from the study. TIA- and headache frequency and modified Rankin scale (mRS) improved (resp. p = 0.001, 0.019, 0.039). Eleven patients (seven children) developed a new infarct during follow-up (31%), five of which were symptomatic. CVR-scores improved significantly (p < 0.0005). The language domain improved (p = 0.029); other domains remained stable. In adults, there was an improvement in QOL. We could not find an association between change in imaging and cognitive scores. Conclusion: In this cohort of Western MMV patients, TIA frequency, headache, CVR, and mRS improved significantly after revascularization. The language domain significantly improved, while others remained stable. We could not find an association between changes in CVR and cognitive scores.

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.

Angiography is critical for visualizing cerebral blood flow in intracranial steno-occlusive diseases. Current 4D magnetic resonance angiography (MRA) techniques primarily focus on macrovascular structures, yet few have quantified hemodynamic timing. This study introduces a novel model to estimate macrovascular arterial transit time (mATT) derived from arterial spin labeling (ASL)-based 4D-MRA. We provide examples of our method that visualize mATT differences throughout the brain of patients with intracranial steno-occlusive disease (moyamoya), as well as changes in mATT resulting from the cerebrovascular reactivity response to an acetazolamide (ACZ) injection. Furthermore, we present a method that projects sparse arterial signals into a 3D native brain-region atlas space and correlates regional mATT with other hemodynamic parameters of interest, such as tissue transit time and cerebrovascular reactivity. This approach offers a non-invasive, quantitative assessment of macrovascular dynamics, with potential to enhance understanding of large-vessel and tissue-level hemodynamics and augment monitoring of treatment outcomes in steno-occlusive disease patients. Furthermore, it sets the stage for more in-depth investigations of the macrovascular contribution to brain hemodynamics.

A healthy vasculature with well-regulated perfusion and pulsatility is essential for the brain. One vascular structure that has received little attention is the carotid siphon. The proximal portion of the siphon is stiff due to the narrow location in the skull base, whilst the distal portion is highly flexible. This flexible part in combination with the specific curves lead to lower pulsatility at the cost of energy deposition in the arterial wall. This deposited energy contributes to damage and calcification. Severe siphon calcification stiffens the distal part of the siphon, leading to less damping of the pulsatility. Increased blood flow pulsatility is a possible cause of stroke and cognitive disorders. In this review, based on comprehensive multimodality imaging, we first describe the anatomy and physiology of the carotid siphon. Subsequently, we review the in vivo imaging data, which indeed suggest that the siphon attenuates pulsatility. Finally, the data as available in the literature are shown to provide convincing evidence that severe siphon calcifications and the calcification pattern are linked to incident stroke and dementia. Interventional studies are required to test whether this association is causal and how an assessment of pulsatility and the siphon calcification pattern can improve personalized medicine, working to prevent and treat brain disease.

Background: Intracranial steno-occlusive disease (SOD) assessment benefits from hemodynamic imaging, but comprehensive evaluation often relies on contrast- or radiation-based techniques. Arterial spin labeling (ASL) provides a non-invasive alternative for quantifying tissue-level perfusion and cerebrovascular reactivity, yet does not capture upstream arterial flow dynamics. As a result, non-invasive assessment of macrovascular hemodynamics for SOD remains limited. This study evaluates whether quantitative 4D-MRA provides complementary arterial information beyond established ASL-derived metrics. Methods: Twelve SOD patients (7 women; age 42.3±25.8 years) underwent multi-delay ASL and 4D-MRA before and after acetazolamide. Cerebrovascular reactivity (CVR), arterial transit time (ATT), macrovascular ATT (mATT), and labeled blood volume (LBV) were quantified. Associations and vasodilatory responses were assessed using linear mixed-effects models. Results: At baseline, mATT correlated with ATT (β=0.66±0.08, p<0.001). Both decreased following acetazolamide (mATT: 1.07±0.03s to 1.01±0.03s, p=0.029; ATT: 1.63±0.07s to 1.40±0.07s, p<0.001). However, changes in mATT and ATT were not associated with CVR. In contrast, CVR was positively associated with ΔLBV (β=8.84, SE=2.43, p=0.01). Case analyses further demonstrated artery-level delayed inflow and vascular steal. Conclusion: Quantitative 4D-MRA provides complementary macrovascular information to ASL in SOD. ΔLBV more consistently reflects cerebrovascular reactivity than transit-based metrics and is sensitive to artery-level delayed inflow and vascular steal.