# Cerebrovascular Reactivity Assessment during Carbon Dioxide Inhalation Using SPECT
###### Abstract  
Background: Perfusion single-photon emission computed tomography (SPECT) using an acetazolamide is an important clinical tool used to assess cerebrovascular reactivity (CVR) in patients, but its use has been limited to clinical diagnostics. This study aimed to preliminarily evaluate the feasibility of perfusion SPECT using carbon dioxide (CO\({}_{2}\)). Methods: Ten healthy subjects participated in two consecutive SPECT scans using CO\({}_{2}\) inhalation. To evaluate brain perfusion after preprocessing, the voxel-by-voxel CVR values were averaged in 13 subgroup regions of interest (ROIs) based on a template. Subsequently, averaged CVR values of each ROI were analyzed based on both cerebellar hemispheres. Results: CVR values in the eight subgroup ROIs, which included vermis, both insula/cingulate, and frontal cortices, showed significant changes (\(p<0.05\)). CVR values were higher in vermis and right insula/cingulate by 3.34% and 3.15%, respectively. Conclusions: This study showed that quantitative SPECT with CO\({}_{2}\) inhalation could be used to evaluate the voxel-based CVR in healthy subjects, which could be beneficial for elucidating induced hypercapnic states and for longitudinally investigating the healthy aging in brain vessels. Furthermore, the cerebrovascular hemodynamic parameters induced by CO\({}_{2}\) could play an important role as a biomarker to evaluate treatment progress in patients with cerebrovascular disease. single-photon-emission computed tomography; SPECT; carbon dioxide; CO\({}_{2}\); cerebrovascular reactivity +
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The challenge of CVR to CO\({}_{2}\) has been investigated in various CVD patients and healthy subjects following CO\({}_{2}\) inhalation, and rCBF has been shown to increase significantly through various methods when CO\({}_{2}\) is inhaled [7; 8]. Therefore, inhalation of air with an appropriate CO\({}_{2}\) concentration during a \({}^{99\text{m}}\)Tc-HMPAO SPECT may be a more valuable and relatively low-cost clinical technique compared to ACZ injection. Previously, many techniques for CVR have been developed to quantify changes in blood flow, especially in the middle cerebral artery (MCA), through vasodilatory challenges such as hypercapnia, apnea, or ACZ administration [8; 9]. In the clinical setting, the use of transcranial Doppler (TCD), positron emission tomography (PET), and blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI) have been applied to evaluate CVR in healthy volunteers and patients [9; 10; 11]. Among others, a BOLD fMRI performed with CO\({}_{2}\) inhalation as a task condition could potentially create a hypercapnic state that could predict both normal and abnormal hemispherical CVR [12; 13]. Furthermore, various stimuli for vasodilation have been used to induce CVR, and several technologies for CVR have been variously introduced with suitable solutions [7; 14]. Recently, a study was performed to conduct an effective diagnosis using multimodal imaging technologies including computer CT, MRI, and SPECT [15]. In contrast, SPECT for CVR evaluation has been considered a potential tool for studying brain function in vivo to determine CVD progression by identifying the magnitude and extent of damage to cerebral vascular flow and for predicting outcomes [16; 17]. The presence and the degree of vasodilation associated with CVR have been significant prognostic indicators in chronic CVD patients with respect to perfusion SPECT. Although it is important to assess CVR using SPECT for a precise diagnosis, there are unresolved methodological concerns, for example, the qualitative and subjective assessment of regional CVR, which is significantly dependent on the examiner [18]. The purpose of this study was to determine the possible use of consecutive \({}^{99\text{m}}\)Tc-HMPAO SPECT imaging with 5% CO\({}_{2}\) inhalation to evaluate CVR in healthy subjects and to calculate the voxel-based CVR values based on the automated anatomical labeling (AAL) template.