In vivo quantification of cerebral r2*-response to graded hyperoxia at 3 tesla

Abstract

Objectives: This study aims to quantify the response of the transverse relaxation rate of the magnetic resonance (MR) signal of the cerebral tissue in healthy volunteers to the administration of air with step-wise increasing percentage of oxygen.

Materials and methods: The transverse relaxation rate (R2*) of the MR signal was quantified in seven volunteers under respiratory intake of normobaric gas mixtures containing 21, 50, 75, and 100% oxygen, respectively. End-tidal breath composition, arterial blood saturation (SaO2), and heart pulse rate were monitored during the challenge. R2* maps were computed from multi-echo, gradient-echo magnetic resonance imaging (MRI) data, acquired at 3.0T. The average values in the segmented white matter (WM) and gray matter (GM) were tested by the analysis of variance (ANOVA), with Bonferroni post-hoc correction. The GM R2*-reactivity to hyperoxia was modeled using the Hill's equation.

Results: Graded hyperoxia resulted in a progressive and significant (P < 0.05) decrease of the R2* in GM. Under normoxia the GM-R2* was 17.2 ± 1.1 s(-1). At 75% O2 supply, the R2* had reached a saturation level, with 16.4 ± 0.7 s(-1) (P = 0.02), without a significant further decrease for 100% O2. The R2*-response of GM correlated positively with CO2 partial pressure (R = 0.69 ± 0.19) and negatively with SaO2 (R = -0.74 ± 0.17). The WM showed a similar progressive, but non-significant, decrease in the relaxation rates, with an increase in oxygen intake (P = 0.055). The Hill's model predicted a maximum R2* response of the GM, of 3.5%, with half the maximum at 68% oxygen concentration.

Conclusions: The GM-R2* responds to hyperoxia in a concentration-dependent manner, suggesting that monitoring and modeling of the R2*-response may provide new oxygenation biomarkers for tumor therapy or assessment of cerebrovascular reactivity in patients.

Keywords: Blood oxygen level dependent (BOLD); R2*; graded hyperoxia; respiratory challenge.

Figure 1

Axial brain images acquired above the body of the lateral ventricle from a typical volunteer are displayed. (a) T1-weighted anatomical reference image acquired using an MR gradient echo sequence (TR/TE =93ms/8ms, Flip Angle =50°, voxel size =0.5 × 0.5 × 1.0 mm³), (b) the corresponding gray matter segmentation mask, and (c) the parametrical R2* map (computed from the pixel-wise fitting of multi-echo MR signals acquired using a gradient echo sequence) of one of the healthy volunteers under normoxia (i.e. during inhalation of medical air with 21% O₂).

Figure 2

Exemplary R2* maps, which were computed, as for Figure 1c, from the pixel-wise fitting of multi-echo MR signals acquired using a gradient echo sequence with TR =93 ms, TE =8, 24, 40, 56, 72, 88 ms, Flip Angle =50°, voxel size =0.5 × 0.5 × 1.0 mm³, of a central axial slice of the brain as acquired during the different stages of the respiratory challenge. A slight but significant decrease of the R2* was measured over the gray matter [Table 2]. A similar trend was observed for the white matter, which, however, was not statistically significant (P = 0.055).

Figure 3

Visual representation of the gray-matter R2* relaxation rates as a function of the percentage of inspired oxygen.

Figure 4

Visual representation of the ratios of the gray-matter R2* values divided by SaO₂ values, as a function of the percentage of inhaled oxygen. The ratio decreased when increasing the O₂ percentage from 21 to 50 % for all volunteers. However, for oxygen percentages above 75% a saturation of the R2* signal was observed.

Figure 5

The mean Bonferroni-corrected gray-matter -ΔR2*-response (baseline and three gas challenges), as defined in Equation [2], as a function of the relative change in oxygen supply. A two-parameter signal saturation curve, as defined in the Equation [3]. (continuous line, ‘Model’) was fitted to the experimental data points (circles, ‘Data’). A potential maximum asymptotic ΔR2*-response in the order of 3.5% was predicted for 3.0 Tesla, while for FiO₂ of.68 half of the maximal response could be inferred.