Cardiovascular risk factors are associated with cerebrovascular reactivity in young adults.

Endothelial dysfunction represents the earliest detectable stage of atherosclerosis, is associated with an increased risk of cardiovascular events, and predicts cardiovascular disease (CVD) more effectively than traditional cardiovascular risk factors. Cerebrovascular reactivity (CVR) provides an index of endothelial function in the brain. Poor CVR is associated with stroke, cerebral small vessel disease, dementia, and even coronary artery disease. Traditional CVD risk factors are associated with low CVR in patients with known CVD and in older cohorts. However, the relationship between cardiovascular risk profile and reduced CVR in young adults who do not yet have CVD is uncertain. We hypothesized that in young adults undergoing routine clinical fMRI examinations for non-vascular disease low CVR measures would be associated with increased cardiovascular risk factors. This cross-sectional study included adults with epilepsy undergoing a 3-Tesla fMRI scan of the brain for mapping of eloquent cortex with a "breath-hold task" to facilitate pre-operative planning for epilepsy-related surgery. Individuals with intracranial masses and those with baseline CVD were excluded. The task consisted of 5½, 20-s blocks of normal breathing interspersed with 20-s blocks of continuous breath holding. In breath hold fMRI scans, a voxel-wise comparison of brain T2 signal to an expected hemodynamic response curve is used to generate maps of voxel-wise t-statistics, indicating the probability that blood flow within a specific voxel had increased in response to changes in blood carbon dioxide levels. Using an axial slice 8 mm superior to the corpus callosum, a mean cerebral t-statistic was calculated for the slice as a comparative global measure of CVR in each patient. We retrospectively reviewed the charts of all individuals to characterize their clinical profile at the time of the fMRI. Based on the distribution of mean t-statistic values the sample was divided into two groups: high t-statistic ("normal reactivity") and low t-statistic value ("abnormal reactivity"). The distribution of cardiovascular risk factors was then compared across groups. Between January 2014 and December 2023, 76 individuals underwent brain fMRI employing a "breath hold task" with suitable image quality for the current analysis (mean ± SD age, 35.46 ± 12.09 yrs.; 31.6 % female). Mean ± SD global CVR T-statistic was 3.97 ± 1.62. Low CVR was defined as a mean T-statistic ≤4.2 (n = 44, 57.9 %). Individuals with abnormal CVR were older (age: 45.1 ± 10.3 vs. 27.0 ± 3.4 yrs., p < 0.001), had a higher frequency of hypertension (31.8 % vs. 14.3 %, p = 0.0069) and hyperlipidemia (18.2 % vs. 3.1 %, p = 0.0449), and had higher systolic (123.5 ± 13.2 vs. 116.9 ± 12.2 mmHg, p = 0.0282) and diastolic blood pressures (77.9 ± 11.8 vs. 72.2 ± 8.9, p = 0.0141). Age, systolic blood pressure and hyperlipidemia were significantly associated with abnormal CVR in univariable and multivariable analyses (age, increase by 10 years OR: 2.00, 95 % CI 1.40-2.78, p = 0.0078; hyperlipidemia OR: 8.54, 95 % CI 1.07-184.9, p = 0.0049, and systolic blood pressure (OR for an increase in 10 mmHg: 1.57, 95 % CI 1.10-2.10, p = 0.0084). Traditional cardiovascular risk factors, specifically age, systolic blood pressure and hyperlipidemia, are significantly associated with abnormal CVR in young adults without baseline CVD or cerebrovascular disease undergoing fMRI for reasons related to a diagnosis of epilepsy.

Sara JDS ，Pillai JJ ，Lerman LO ，Lerman A ，Welker K ... -  《-》

A practical modification to a resting state fMRI protocol for improved characterization of cerebrovascular function.

Cerebrovascular reactivity (CVR), defined here as the Blood Oxygenation Level Dependent (BOLD) response to a CO2 pressure change, is a useful metric of cerebrovascular function. Both the amplitude and the timing (hemodynamic lag) of the CVR response can bring insight into the nature of a cerebrovascular pathology and aid in understanding noise confounds when using functional Magnetic Resonance Imaging (fMRI) to study neural activity. This research assessed a practical modification to a typical resting-state fMRI protocol, to improve the characterization of cerebrovascular function. In 9 healthy subjects, we modelled CVR and lag in three resting-state data segments, and in data segments which added a 2-3 minute breathing task to the start of a resting-state segment. Two different breathing tasks were used to induce fluctuations in arterial CO2 pressure: a breath-hold task to induce hypercapnia (CO2 increase) and a cued deep breathing task to induce hypocapnia (CO2 decrease). Our analysis produced voxel-wise estimates of the amplitude (CVR) and timing (lag) of the BOLD-fMRI response to CO2 by systematically shifting the CO2 regressor in time to optimize the model fit. This optimization inherently increases gray matter CVR values and fit statistics. The inclusion of a simple breathing task, compared to a resting-state scan only, increases the number of voxels in the brain that have a significant relationship between CO2 and BOLD-fMRI signals, and improves our confidence in the plausibility of voxel-wise CVR and hemodynamic lag estimates. We demonstrate the clinical utility and feasibility of this protocol in an incidental finding of Moyamoya disease, and explore the possibilities and challenges of using this protocol in younger populations. This hybrid protocol has direct applications for CVR mapping in both research and clinical settings and wider applications for fMRI denoising and interpretation.

Stickland RC ，Zvolanek KM ，Moia S ，Ayyagari A ，Caballero-Gaudes C ，Bright MG ... -  《-》

Comparing end-tidal CO(2), respiration volume per time (RVT), and average gray matter signal for mapping cerebrovascular reactivity amplitude and delay with breath-hold task BOLD fMRI.

Cerebrovascular reactivity (CVR), defined as the cerebral blood flow response to a vasoactive stimulus, is an imaging biomarker with demonstrated utility in a range of diseases and in typical development and aging processes. A robust and widely implemented method to map CVR involves using a breath-hold task during a BOLD fMRI scan. Recording end-tidal CO2 (PETCO2) changes during the breath-hold task is recommended to be used as a reference signal for modeling CVR amplitude in standard units (%BOLD/mmHg) and CVR delay in seconds. However, obtaining reliable PETCO2 recordings requires equipment and task compliance that may not be achievable in all settings. To address this challenge, we investigated two alternative reference signals to map CVR amplitude and delay in a lagged general linear model (lagged-GLM) framework: respiration volume per time (RVT) and average gray matter BOLD response (GM-BOLD). In 8 healthy adults with multiple scan sessions, we compare spatial agreement of CVR maps from RVT and GM-BOLD to those generated with PETCO2. We define a threshold to determine whether a PETCO2 recording has "sufficient" quality for CVR mapping and perform these comparisons in 16 datasets with sufficient PETCO2 and 6 datasets with insufficient PETCO2. When PETCO2 quality is sufficient, both RVT and GM-BOLD produce CVR amplitude maps that are nearly identical to those from PETCO2 (after accounting for differences in scale), with the caveat they are not in standard units to facilitate between-group comparisons. CVR delays are comparable to PETCO2 with an RVT regressor but may be underestimated with the average GM-BOLD regressor. Importantly, when PETCO2 quality is insufficient, RVT and GM-BOLD CVR recover reasonable CVR amplitude and delay maps, provided the participant attempted the breath-hold task. Therefore, our framework offers a solution for achieving high quality CVR maps in both retrospective and prospective studies where sufficient PETCO2 recordings are not available and especially in populations where obtaining reliable measurements is a known challenge (e.g., children). Our results have the potential to improve the accessibility of CVR mapping and to increase the prevalence of this promising metric of vascular health.

Zvolanek KM ，Moia S ，Dean JN ，Stickland RC ，Caballero-Gaudes C ，Bright MG ... -  《-》

Comparison of BOLD cerebrovascular reactivity mapping and DSC MR perfusion imaging for prediction of neurovascular uncoupling potential in brain tumors.

Pillai JJ ，Zacà D 《-》

Breath-hold BOLD fMRI without CO(2) sampling enables estimation of venous cerebral blood volume: potential use in normalization of stimulus-evoked BOLD fMRI data.

Biondetti E ，Chiarelli AM ，Germuska M ，Lipp I ，Villani A ，Caporale AS ，Patitucci E ，Murphy K ，Tomassini V ，Wise RG ... -  《-》