# Cerebrovascular Reactivity Assessment during Carbon Dioxide Inhalation Using SPECT
## 4 Discussion  
In this study, we assessed the feasibility of measuring CVR using a \({}^{99\text{m}}\)Tc-HMPAO SPECT with 5% CO\({}_{2}\) inhalation in healthy subjects. Unlike previous studies, our voxel-wise CVR map was constructed based on an AAL brain template with 116 ROIs [20,22]. An automated processing program quantitatively measured the mean CVR value of voxels in each subgroup ROI to elucidate the effect of the hypercaptic state on a healthy human brain. We found that this quantitative CVR analysis of the subgroup ROIs could be used as an exploratory approach to assess vascular reactivity in healthy subjects [23,24]. The findings demonstrated that CO\({}_{2}\) perfusion SPECT could provide evidence for the relationship between the reactive effect of CO\({}_{2}\) and CBF in specific vascular territories. Using the CVR maps obtained from all the subjects, the relative CVR values in eight subgroup ROIs, including the right temporal cortex, vermis, left and right insula/cingulate, left and right frontal cortex, and left parietal and central cortex, showed significant changes (\(p<0.05\)) relative to the CVR value in the cerebellum. The results showed high relative mean CVR values in the right and left insula/cingulate cortex (ROI #04 and #05, respectively) and in the cortical areas other than the vermis (ROI #03), and low relative mean CVR values in the right and left occipital cortex (ROI #08 and #09, respectively). According to previous studies, an increase in CO\({}_{2}\) concentration in inspired air is known to cause vascular changes in the brain, including increased CBF and higher CO\({}_{2}\) and O\({}_{2}\) concentrations in the blood [25]. In the present study, the insula/cingulate cortex (anterior vascular territory), which receives blood through the anterior cerebral artery (ACA), and the occipital cortex (posterior vascular territory), which receives blood through the posterior cerebral artery (PCA), did not show significant changes like the cerebellum. This suggests that CO\({}_{2}\) has various effects on vascular territories, which has been shown in several studies in which major cerebral arteries, such as the MCA, PCA, and ACA, undergo some changes after CO\({}_{2}\) is applied in patients and healthy subjects [26,27]. In contrast to previous studies investigating the feasibility of CVR measurements using CO\({}_{2}\) on patients, few studies using SPECT and CO\({}_{2}\) inhalation have been conducted on healthy subjects [8,28]. CO\({}_{2}\) has fewer side effects than ACZ, is more likely to cause blood flow changes, which allows researchers to evaluate CVR on healthy subjects as well as patients, and is commonly used in BOLD fMRI studies [12,13]. Furthermore, although SPECT is a standard tool for perfusion imaging in the clinical diagnosis of patients, it is not sufficiently used for quantitative evaluation and objective diagnosis. Therefore, the proposed quantitative CVR mapping technique in this study could provide the basis for the development of objective and clinical diagnostic methods in future SPECTVR studies and for a direct comparison between SPECT and fMRI CVR measurements. Furthermore, this technique can be used as a medical check-up tool by analyzing the degree of change through follow-up tests which primarily prevent cerebrovascular disease, and it can be used to predict the penumbra area of patients with acute cerebral infarction, and to determine the degree of autoregulation damage or recovery of cerebral vessels [29]. Lastly, it can help determine the proper timing of vascular bypass operation for moyamoya disease, a rare cerebrovascular disease, without any vasodilation drug [30]. However, this study has some limitations. First, only a small number of young, healthy volunteers were included. Moreover, gender inequality with small groups can make it difficult to draw definitive conclusions. Further studies should examine optimal CO\({}_{2}\) concentrations for providing reliable and reproducible CVR values [31].