Blood oxygenation level‐dependent (BOLD)‐based techniques for the quantification of brain hemodynamic and metabolic properties – theoretical models and experimental approaches

Abstract

Quantitative evaluation of brain hemodynamics and metabolism, particularly the relationship between brain function and oxygen utilization, is important for understanding normal human brain operation as well as pathophysiology of neurological disorders. It can also be of great importance for evaluation of hypoxia within tumors of the brain and other organs. A fundamental discovery by Ogawa and co-workers of the BOLD (Blood Oxygenation Level Dependent) contrast opened a possibility to use this effect to study brain hemodynamic and metabolic properties by means of MRI measurements. Such measurements require developing theoretical models connecting MRI signal to brain structure and functioning and designing experimental techniques allowing MR measurements of salient features of theoretical models. In our review we discuss several such theoretical models and experimental methods for quantification brain hemodynamic and metabolic properties. Our review aims mostly at methods for measuring oxygen extraction fraction, OEF, based on measuring blood oxygenation level. Combining measurement of OEF with measurement of CBF allows evaluation of oxygen consumption, CMRO2. We first consider in detail magnetic properties of blood – magnetic susceptibility, MR relaxation and theoretical models of intravascular contribution to MR signal under different experimental conditions. Then, we describe a “through-space” effect – the influence of inhomogeneous magnetic fields, created in the extravascular space by intravascular deoxygenated blood, on the MR signal formation. Further we describe several experimental techniques taking advantage of these theoretical models. Some of these techniques - MR susceptometry, and T2-based quantification of oxygen OEF – utilize intravascular MR signal. Another technique – qBOLD – evaluates OEF by making use of through-space effects. In this review we targeted both scientists just entering the MR field and more experienced MR researchers interested in applying advanced BOLD-based techniques to study brain in health and disease.

Tissue Oxygen Saturation Mapping with Magnetic Resonance Imaging

“…5 We evaluated the validity of this assumption using healthy rats submitted to various brain oxygenation challenges and found a strong correlation between MR_StO 2 (from mqBOLD) and StO 2 estimates from blood gas in the range of 20-90%. This technique could be further refined by taking into account the variations of magnetic susceptibilities across tissue types, as recently proposed in Yablonskiy et al 28 However, this would firstly require a procedure to assign a tissue type to each voxel and to handle partial volume effects. This refinement could be particularly useful in white matter, where the low MR_StO 2 values observed with our approach might be due to the presence of myelin fibers that also shorten T 2 *.…”

The physics of functional magnetic resonance imaging (fMRI)

“…A major ongoing goal of this work is to develop methods for separating the effects of CBF and CMRO 2 and thus provide tools to make fMRI into a quantitative probe of brain physiology. These ideas are discussed in more detail in several recent reviews [21, 108–110]. Here the focus is on signal decay, the dominant mechanism exploited in fMRI.…”

Mapping of cerebral metabolic rate of oxygen using dynamic susceptibility contrast and blood oxygen level dependent MR imaging in acute ischemic stroke

“…However, transverse relaxation times T2 and T2* alone are not valid indicators of blood oxygenat i o n b e c a u s e t h e y a r e i n f l u e n c e d b y t h e t o t a l deoxyhemoglobin content within a voxel, i.e., the blood volume, blood flow, and a number of additional influences [25]. Because of this, more sophisticated methods have been developed to estimate CMRO 2 [2,26,48], which are based on an acceptably fast semi-quantitative measurements of the relative oxygen extraction fraction (rOEF) with a reasonable volume coverage [25]. This new BOLD-based method for rOEF mapping has been applied in glioma patients [25,43], yielding promising results [43], and was multiplied by the standard dynamic DSC voxel-by-voxel-derived CBF in order to calculate the relative CMRO 2 (rCMRO 2 ).…”

“…Several groups previously attempted to quantify the BOLD effect [3,16,47,48]. The effect depends on susceptibility differences between diamagnetic tissue and blood, whose magnetic properties depend on its oxygenation status: upon deoxygenation, hemoglobin turns from diamagnetic to paramagnetic.…”