Scientists and clinician who are interested in MS imaging research Cerebrovascular reactivity (CVR) is a robust measure of vascular function – the capacity of regulation of blood flow in response to vasoactive stimuli (e.g., CO₂) via changes in cerebral arterial resistance. In healthy condition, CVR serves to modulate and maintain the optimal blood flow to meet the energy demand by neurovascular coupling during neuronal tasks. The defected CVR in a disease state can cause transient states of inefficient blood delivery during neural activity leading to subsequent neurodysfunction and degeneration. CVR is commonly measured with mild hypercapnia (breathing 5% CO₂) perfusion (ie. arterial spin labeling or ASL) (1) or BOLD (2) MRI. It is well known that the changes of blood CO₂ level can also alter the venous oxygenation level by increasing flow and oxygen, therefore, the purpose of this study was to test the feasibility to measure CVR using hypercapnia MRI with quantitative susceptibility mapping (QSM) and T2-relaxation-under-spin-tagging (TRUST) (3) techniques.Seven subjects underwent MRI scans at 3T under room air and hypercapnia (breathing a gas mixture of 5% CO2, 21%O₂, 74%N₂) conditions to assess whole brain CVR measured by QSM and TRUST MRI. QSM was generated using a susceptibility-weighted imaging (SWI) acquired with parameters of TR/TE/FA: 32/20/15 (2’37”). TRUST MRI is a well-established quantitative technique (3) for cerebral venous oxygenation (Yv). It starts with a spin labeling module with labeling slab placed above the imaging slice to tag the superior saggital sinus (SSS) pure venous blood and measures T2-relaxation time using a series of non-slice-selective T2-preparation pulses in order to quantify blood T2. The SSS blood T2 was then converted to Yv using a calibration plot. The details of imaging sequences and image processing can be found in our previous studies. Image processing of QSM used the algorithm described previously, first, the phase images were unwrapped using SWIM algorithm with Laplacian unwrapping and SHARP background removal. Images at normocapnia were threshold at 70 ppb and area that not belongs to veins subtract from the analysis (ie basal ganglia or artifact) to have pure venous structures segmented. The breathing apparatus is composed of gas delivery through mouthpiece, switching from room air to CO2, and endtidal CO2 recording, please find details in the previous study (2). The QSM-based CVR and TRUST-based CVR are calculated as normocapnia to hypercapnia percent QSM changes (from whole segmented venous blood voxels) and percent Yv changes (from SSS) per EtCO₂ change (mmHg), respectively.The EtCO₂ values increased significantly between the normocapnic and hypercapnic QSM or TRUST scans (37.7±7.0 to 48.6±5.5, p=0.0006). There was no significant difference between normocapnic and hypercapnic EtCO2 levels during the QSM and the TRUST runs. There was a significantly decreased QSM from venous blood voxels (p=0.0007) and increased Yv (p=0.006) during hypercapnia breathing as compared to normocapnia breathing. CVR values based on QSM are 0.033±0.006 %QSM/mmHg EtCO₂ and based on TRUST are 0.025±0.011 %QSM/mmHg EtCO2, which are not significantly different (p=0.24). As shown in Figure 1, Figure 2 showed the comparison of average QSM-based CVR and TRUST-based CVR. The current study confirms that CVR calculated based on QSM and TRUST are highly correlated, and their average CVR value is very with the previous reported valued based hypercapnia perfusion MRI (1). Since CO₂ is considered a potent vasodilator and has minimal effect on neuronal activity, the blood oxygenation changes on QSM and TRUST are principally reflect vascular modulation or CVR. However, QSM can provide much higher spatial resolution and TRUST has much quicker scan times as opposed to arterial ASL perfusion or BOLD MRI for CVR quantification, which are all critical in clinical settings.