Validation of oxygen extraction fraction measurement by qBOLD technique

Abstract

Measurement of brain tissue oxygen extraction fraction (OEF) in both baseline and functionally activated states can provide important information on brain functioning in health and disease. The recently proposed quantitative BOLD (qBOLD) technique is MRI-based and provides a regional in vivo OEF measurement (He and Yablonskiy, MRM 2007, 57:115-126). It is based on a previously developed analytical BOLD model and incorporates prior knowledge about the brain tissue composition including the contributions from grey matter, white matter, cerebrospinal fluid, interstitial fluid and intravascular blood. The qBOLD model also allows for the separation of contributions to the BOLD signal from OEF and the deoxyhemoglobin containing blood volume (DBV). The objective of this study is to validate OEF measurements provided by the qBOLD approach. To this end we use a rat model and compare qBOLD OEF measurements against direct measurements of the blood oxygenation level obtained from venous blood drawn directly from the superior sagittal sinus. The cerebral venous oxygenation level of the rat was manipulated by utilizing different anestheisa methods. The study demonstrates a very good agreement between qBOLD approach and direct measurements.

FIG. 1

Representative data and fitting curves obtained with the 3D GESSE sequence for a rat under alpha-chloralose anesthesia. Contributions from all compartments are shown. a: Signal (square) and the fitted profile (dashed line) for the selected voxel. b: High resolution anatomic T₁-weighted image with the selected voxel shown by a rectangle. c: The extravascular signal contribution after removing signals from ISF/CSF and intravascular blood and adjusting for the R₂ decay (multiplying by the factor exp[+ R₂ TE]). The solid lines correspond to the extrapolated signal profile from the asymptotic behavior at long echo times, demonstrating the expected quadratic behavior around the spin echo. d: Fitting residual. e: Magnitude of the ISF/CSF signal. f: Real part of the intravascular blood signal.

FIG. 2

Examples of the maps of estimated venous blood oxygen saturation level obtained with the qBOLD technique from the rat under isoflurane (middle) and alpha-chloralose (right) anesthesia. The color bar shows the blood oxygenation level in %. The leftmost image is the T₁-weighted anatomic image. The venous blood oxygen saturation level measured using the i-STAT analyzer was 77% for isoflurane and 67% for alpha-chloralose, respectively. Mean values of venous blood oxygen saturation level calculated from the images shown are 77% under isoflurane anesthesia and 62% under alpha-chloralose anesthesia.

FIG. 3

Comparison of venous oxygen saturation level [Y × 100%] measured with the qBOLD technique with the oxygenation of venous blood, SvO₂, from blood samples drawn directly from the superior sagittal sinus and measured with a blood gas analyzer (average of before and after MR scan). Because the results from the blood gas analyzer provide only integrated SvO₂ values for the entire brain, the results from the qBOLD measurements are also shown averaged across the entire brain. Data marked with triangles indicate rats anesthetized with isoflurane, circles indicate rats anesthetized with alpha-chloralose, and the solid curve is a linear regression fit to the data.

FIG. 4

Representative maps of rat brain parameters determined from qBOLD model. The top leftmost image is a high resolution T₁-weighted anatomic image. The rest of maps are venous blood oxygenation level (%), DBV fraction (%), apparent R₂ for the combined brain tissue and ISF/CSF (s⁻¹) and R₂ for the brain tissue (s⁻¹), ISF/CSF signal fraction at spin echo time (%), ISF/CSF frequency shift (Hz) and the effective magnetization density (relative to parenchyma tissue) of intravascular blood signal. The rat in this study was under alpha-chloralose anesthesia with direct measured venous blood oxygenation level of 52%.