Approaches to Brain Stress Testing: BOLD Magnetic Resonance Imaging with Computer-Controlled Delivery of Carbon Dioxide

Abstract

BackgroundAn impaired vascular response in the brain regionally may indicate reduced vascular reserve and vulnerability to ischemic injury. Changing the carbon dioxide (CO2) tension in arterial blood is commonly used as a cerebral vasoactive stimulus to assess the cerebral vascular response, changing cerebral blood flow (CBF) by up to 5–11 percent/mmHg in normal adults. Here we describe two approaches to generating the CO2 challenge using a computer-controlled gas blender to administer: i) a square wave change in CO2 and, ii) a ramp stimulus, consisting of a continuously graded change in CO2 over a range. Responses were assessed regionally by blood oxygen level dependent (BOLD) magnetic resonance imaging (MRI).Methodology/Principal FindingsWe studied 8 patients with known cerebrovascular disease (carotid stenosis or occlusion) and 2 healthy subjects. The square wave stimulus was used to study the dynamics of the vascular response, while the ramp stimulus assessed the steady-state response to CO2. Cerebrovascular reactivity (CVR) maps were registered by color coding and overlaid on the anatomical scans generated with 3 Tesla MRI to assess the corresponding BOLD signal change/mmHg change in CO2, voxel-by-voxel. Using a fractal temporal approach, detrended fluctuation analysis (DFA) maps of the processed raw BOLD signal per voxel over the same CO2 range were generated. Regions of BOLD signal decrease with increased CO2 (coded blue) were seen in all of these high-risk patients, indicating regions of impaired CVR. All patients also demonstrated regions of altered signal structure on DFA maps (Hurst exponents less than 0.5; coded blue) indicative of anti-persistent noise. While ‘blue’ CVR maps remained essentially stable over the time of analysis, ‘blue’ DFA maps improved.Conclusions/SignificanceThis combined dual stimulus and dual analysis approach may be complementary in identifying vulnerable brain regions and thus constitute a regional as well as global brain stress test.

Altered cerebrovascular reactivity velocity in mild cognitive impairment and Alzheimer's disease

“…The simple on-off "square wave" CO 2 stimulus is straightforward to apply and a robust probe for CVR dynamics (Mutch et al, 2012). Our results show that a simple nasal cannula is sufficient to induce significant whole-brain BOLD response under CO 2 challenge with acceptable acquisition time, and the setup necessary for the CO 2 clinical protocol does not interfere with the structural MRI typically performed in routine workup on cognitive decline.…”

“…The application of carbon dioxide (CO 2 ) induces vasodilation, which can be assessed in the entire brain parenchyma using blood oxygen leveledependent (BOLD) MRI (Cohen et al, 2002;Haller et al, 2006Haller et al, , 2008Kassner and Roberts, 2004;Mutch et al, 2012;Ziyeh et al, 2005). Beyond changes in CVR amplitude, 1 previous functional magnetic resonance imaging (fMRI) study (Cantin et al, 2011) observed that a different slope of response to hypercapnia was found in MCI and AD patients than in control subjects, suggesting that the temporal dynamics of CVR may differ.…”

Altered intraoperative cerebrovascular reactivity in brain areas of high-grade glioma recurrence

“…6 Improvements of BOLD CVR methodologies have been proposed [13,15] and may increase sensitivity and quantification of (regional) CVR measurements in subjects with high-grade cerebral glioma.…”

Quantitative mapping of cerebrovascular reactivity using resting-state BOLD fMRI: Validation in healthy adults

“…CO 2 is a potent vasodilator, triggering changes in vascular tone through the arterial baroflex. PETCO 2 changes can be induced through manually adjusted administration of blended gases (Bandettini and Wong, 1997 ;Cohen et al, 2004;Yezhuvath et al, 2009), end-tidal forcing (Poulin et al, 1996) or more recently, computerized PETCO 2 targeting (Conklin et al, 2011;Han et al, 2011;Mandell et al, 2011;Mandell et al, 2008;Mark et al, 2010;Mikulis et al, 1989;Mutch et al, 2012;Prisman et al, 2008;Slessarev et al, 2007;Spano et al, 2013;Vesely et al, 2001). The latter method provides immediate and robust PETCO 2 changes, and we have used it extensively in our own work (Chen and Pike, 2010a;Chen and Pike, 2010b;Halani et al, 2015).…”