Sinusoidal CO2 respiratory challenge for concurrent perfusion and cerebrovascular reactivity MRI

Abstract

Introduction: Deoxygenation-based dynamic susceptibility contrast (dDSC) has previously leveraged respiratory challenges to modulate blood oxygen content as an endogenous source of contrast alternative to gadolinium injection in perfusion-weighted MRI. This work proposed the use of sinusoidal modulation of end-tidal CO2 pressures (SineCO2), which has previously been used to measure cerebrovascular reactivity, to induce susceptibility-weighted gradient-echo signal loss to measure brain perfusion.Methods:SineCO2 was performed in 10 healthy volunteers (age 37 ± 11, 60% female), and tracer kinetics model was applied in the frequency domain to calculate cerebral blood flow, cerebral blood volume, mean transit time, and temporal delay. These perfusion estimates were compared against reference techniques, including gadolinium-based DSC, arterial spin labeling, and phase contrast.Results: Our results showed regional agreement between SineCO2 and the clinical comparators. SineCO2 was able to generate robust CVR maps in conjunction to baseline perfusion estimates.Discussion: Overall, this work demonstrated feasibility of using sinusoidal CO2 respiratory paradigm to simultaneously acquire both cerebral perfusion and cerebrovascular reactivity maps in one imaging sequence.

Non-Invasive Perfusion MR Imaging of the Human Brain via Breath-Holding

“…While we have compared literature values to our results, a direct subject-wise bhDSC vs Gd-DSC comparison will allow for a stronger validation of the technique’s utility in perfusion imaging. Although, another group that induced hypercapnia with a gas control system to obtain DSC metrics found relatively high CBF regional correlation with Gd-DSC (Vu et al ., 2023)—this is very promising given that our technique relies on a similar physiological mechanism. As well, the clinical utility of the bhDSC technique should be validated in different patient cohorts, to determine whether all or a subset of those with vascular brain pathology will benefit from bhDSC alone or in combination with additional perfusion imaging techniques (i.e., ASL).…”

“…[1], [2], [3], [9] Of note, all DSC perfusion metrics are technically relative, in that they are dependent on numerous acquisition and analysis parameters, as has been previously documented. [10], [11] While gadolinium (Gd), an exogenous paramagnetic metal, is the standard contrast agent used for DSC, researchers have recently exploited the paramagnetic properties of deoxyhemoglobin (dOHb) as an endogenous contrast alternative [11], [12], [13], [14], [15], [16] -in essence, both Gd and dOHb induce T2* signal changes that can be exploited in a DSC analysis. However, Gd is limited in that it is invasive, expensive, and toxic in certain patient populations.…”

“…While gadolinium (Gd), an exogenous paramagnetic metal, is the standard contrast agent used clinically for DSC, researchers have recently exploited the paramagnetic properties of deoxyhemoglobin (dOHb) as an endogenous contrast alternative (Lee et al ., 2022; Poublanc et al ., 2021; Sayin et al ., 2022; Schulman et al ., 2023; Vu et al ., 2021; Vu et al ., 2023)—in essence, both Gd and dOHb induce T 2 * signal changes that can be exploited in a DSC analysis. However, Gd is limited in that it is invasive, expensive, and exhibits toxicity in certain patient populations (Kanda, et al ., 2015; Rogowska et al ., 2018; Schlaudecker and Bernheisel, 2009).…”

“…However, Gd is limited in that it is invasive, expensive, and exhibits toxicity in certain patient populations (Kanda, et al ., 2015; Rogowska et al ., 2018; Schlaudecker and Bernheisel, 2009). On the other hand, generating dOHb contrast has thus far relied on gas control systems that modify dOHb concentration in the blood through the induction of hypoxia (Lee et al ., 2022; Poublanc et al ., 2021; Sayin et al ., 2022; Schulman et al ., 2023; Vu et al ., 2021), hyperoxia (MacDonald et al ., 2018), or hyper/hypocapnia (Vu et al ., 2023). Given the associated cost, set-up time, and expertise required for gas control system utilization, the widespread clinical implementation of dOHb contrast as an alternative to Gd is currently limited.…”

Mapping cerebral perfusion in mice under various anesthesia levels using highly sensitive BOLD MRI with transient hypoxia

“…As an alternative to the hypoxic stimulus, CO 2 or O 2 challenge may be considered for perfusion studies. Both CO 2 and O 2 challenges induce BOLD responses mostly in the venous vasculature (38)(39)(40) but much less at the large arteries due to a high baseline oxygenation level of ~0.98. Thus, determining the arterial input function becomes problematic.…”