Nitrogen Gas Induced Acute Hypoxia as a Contrast Agent in Functional Magnetic Resonance Imaging

Introduction:: Gadolinium-based dynamic susceptibility contrast (DSC) is an MRI technique capable of resolving spatiotemporal hemodynamics maps that uses a gadolinium contrast injection and time resolved gradient echo imaging. Unfortunately, gadolinium is associated with nephrogenic systemic fibrosis, requires venous access and bioaccumulates in the brain[1], [2]. Nitrogen induced hypoxia offers a safe, contrast free alternative to gadolinium and causes a similar paramagnetic contrast bolus by increasing the concentration of deoxyhemoglobin in arterial blood. To better characterize deoxyhemoglobin DSC (dDSC), we first aimed to quantify the physiological responses to systemic hypoxia, specifically its duration and intensity. This study aims to determine the relationship between intake of 100% medical-grade nitrogen gas and the various parameters of hypoxic desaturation.


Materials and Methods:: All studies were performed using an IRB approved protocol with informed consent from subjects. A custom ventilation circuit (Hans Rudolph, Shawnee, KS) was used to supply 100% medical grade nitrogen (Airgas, Radnor, PA) to subjects. A facemask and one-way valves were used to prevent rebreathing. An inline TSD117-A spirometer (BIOPAC systems, Goleta, CA) measured tidal volumes, and arterial saturation (SpO2%) and heart rate were also measured (Nonin Medical, Plymouth, MN). Subjects were asked to inhale nitrogen for three, four, and five breaths across three separate trials as determined by abdominal movement, and data was collected until 15 seconds after a full SpO2% recovery. Measurements were collected on 6 healthy subjects (4 female, 2 male), and all calculations and processing were performed in MATLAB (Natick, MA).


Results, Conclusions, and Discussions:: A characteristic SpO2% curve is depicted in Figure 1A. To quantify the strength of a hypoxic bolus, a parameter called desaturation power was defined as the time integral of the nitrogen-induced decrease in SpO2%, percentage of deoxyhemoglobin in blood (SpdO2%). This quantity is shaded in red in the characteristic curve. Figure 1B depicts a plot of the hypoxia-induced desaturation power with respect to the amount of nitrogen gas inhaled, and Figure 1C demonstrates the positive correlation between nitrogen exposure time and desaturation bolus duration, calculated as the time that each subject’s SpO2% levels fall below 96% of their respective maximum SpO2% levels. From the results, inhaling more nitrogen causes stronger and longer boluses of SpdO2%. However, the exact relation between nitrogen inhaled with respect to other physiological parameters needs to be quantified in future experiments. This study shows that hypoxia can be induced with nitrogen gas and that there is a linear relationship between the duration of nitrogen exposure and the duration of the desaturation response peripherally. However, the exact relationship with parameters such as height, lung capacity, and gender require more investigation. Additional study can further quantify and model the correlation between individual physiological responses to hypoxia and later the magnitude of BOLD signal.


Acknowledgements (Optional): :

References (Optional): : [1] C. Vu et al., “Quantitative perfusion mapping with induced transient hypoxia using BOLD MRI,” Magn. Reson. Med., vol. 85, no. 1, pp. 168–181, Jan. 2021.

[2] B. T. Bråtane, R. P. Walvick, C. Corot, E. Lancelot, and M. Fisher, “Characterization of gadolinium-based dynamic susceptibility contrast perfusion measurements in permanent and transient MCAO models with volumetric based validation by CASL,” J. Cereb. Blood Flow Metab., vol. 30, no. 2, pp. 336–342, Feb. 2010.