Imaging of Oxygenation Using MR

Dmitriy Yablonskiy¹

¹Mallinckrodt Institute of Radiology

Synopsis

Introduction

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. Most of the currently used methods are based on measuring blood oxygenation level and directly related to it oxygen extraction fraction, OEF. Combining measurement of OEF with measurement of CBF allows evaluation of oxygen consumption, CMRO₂. In my talk I will first discuss magnetic properties of blood – magnetic susceptibility and MR relaxation. Then, I will 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 I describe several experimental techniques for measuring tissue hemodynamic properties. 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.

Fick’s principle

According to Fick’s principle (1), CMRO₂ can be calculated by using the following relationship:

CMRO₂ = CBF • C_blood • (Ya –Yv) [1]

where Ya and Yv are oxygenation levels of arterial and venous blood (i.e., the fraction of hemoglobin in the form of oxyHb; Y = 1 corresponds to fully oxygenated blood and Y =0 corresponds to fully deoxygenated blood); and Cblood is blood oxygen carrying capacity. Strictly speaking, Eq. [1] corresponds to oxygen combined with hemoglobin, ignoring oxygen dissolved in blood plasma which has much lower concentration but can also be taken into consideration (2). Usually dissolved oxygen does not exceed 1.5% of total oxygen in blood though it can be higher in abnormal conditions, e.g. hyperoxia (3). By introducing blood hematocrit level Hct and oxygen carrying capacity of red blood cells (C_RBC), Eq. [1] can be written as follows:

CMRO₂ = C_RBC • CBF • Hct • Ya • OEF [2]

where oxygen extraction fraction OEF is defined as (Ya – Yv)/Ya. According to Eqs. [1], [2], if CBF and OEF are known, oxygen consumption CMRO2 can be calculated. Most of the current MR methods of measuring OEF are based, in fact, on measuring blood oxygenation level.

Blood Oxygenation and MR Signal

One of the important parameters characterizing magnetic properties of all tissues is their magnetic susceptibility χ – a proportionality coefficient between tissue magnetization, M, induced by an external magnetic field B0 (M = χ B0) and the magnetic field strength. Most components of biological tissues, such as water, proteins, lipids, are diamagnetic (their magnetic susceptibility χ is negative). The diamagnetism is a common property of all atoms and molecules; it is due to the effect of changing microscopic atomic currents of orbiting electrons, sometimes called Ampèrian currents, in the presence of magnetic field B0. If atoms or molecules contain uncompensated electronic spin moments (that is always accompanied by magnetic moment), they also exhibit additional magnetic susceptibility which is positive and is called paramagnetic susceptibility. The paramagnetic effect is due to “orientational nature” of magnetic field that tends to align electron spin magnetic moments against “de-orientational nature” of thermal motion. Biologically relevant examples of paramagnetic molecules include non-heme iron and heme iron in deoxyhemoglobin (see detail discussion in (4-6)), and dissolved oxygen molecule O2. Importantly, heme iron is paramagnetic because of its state. When heme iron combines with oxygen, it changes its electronic configuration and the total spin magnetic moment of heme complex becomes zero (7,8). When heme iron releases oxygen, it returns to a paramagnetic state. Hence, magnetic state of heme iron can be used as a biomarker of blood oxygenation level. When blood passes through the capillary bed and releases oxygen, the state of heme iron changes from zero-spin at the arterial side to a high spin at the venous side. Due to these reversible changes of heme complexes in deoxygenated red blood cells (RBC) (7,8), the blood vessel network in biological tissues modifies MR signal. Importantly, this modification depends on blood oxygenation level. This phenomenon forms the basis of the BOLD (blood oxygen level dependent) contrast in MRI. Two effects should be separated – intravascular and extravascular. The intravascular effect is due to the inhomogeneous magnetic fields created by red blood cells in blood (9). The extravascular (through-space) effect is mainly due to inhomogeneous magnetic fields created by blood vessels in the surrounding tissue (10). Because these magnetic field inhomogeneities are tissue specific, they can provide important information on tissue hemodynamic properties.

Blood Magnetic Susceptibility

A detailed theoretical consideration of blood magnetic susceptibility and the detailed experimental studies employing in vitro samples that were well representative of human blood in situ were provided in (11). The magnetic susceptibility of whole blood is determined by a weighted sum of magnetic susceptibilities of RBC and plasma:

χ_blood = Hct • χ_RBC + (1 – Hct) • χ_plasma [3]

Thus, the magnetic susceptibility of RBCs can be described as (11):

χ_RBC = -0.736 + Δχ₀ • (1 – Y) [ppm] [4] χ_plazma = -0.722 ppm [5]

where Y is blood oxygenation level and the susceptibility difference between completely deoxygenated (Y = 0) and completely oxygenated (Y = 1) RBC is equal to

Δχ₀ = 0.27 ppm [6]

Equation [6] was confirmed by two independent MR and SQUID magnetometer measurements in (11) and recently by detail magnetic susceptometry measurements (12).

Extravascular MR Signal

The total MR signal includes signal from blood and from surrounding tissue where inhomogeneous magnetic field is induced due to the susceptibility difference Δχ between blood containing paramagnetic deoxyHb and tissue. Thus, spins of water protons in the extravascular space sustain different phase shift, leading to MR signal decay. Several theoretical approaches have been proposed to calculate MR signal. Detail discussion and references can be found in (2).

Experimental Methods

qBOLD - Quantitative Mapping of Brain Hemodynamics and Metabolism

One of the experimental methods for quantifying brain hemodynamic properties is quantitative BOLD (qBOLD). This technique was proposed in (13) and verified on animal model in (14). It is based on a theory of MR signal formation in the presence of blood vessel network (15), experimental method GESSE proposed and verified on phantoms in (16) and a realistic consideration of multi-compartment tissue structure. qBOLD technique based on gradient echo acquisition was developed in (17). A robustness of qBOLD quantification can be improved by independent measurements of some model parameters. In the framework of a single compartment model this idea was implemented by Christen, et al, (18-20). Further improvements in qBOLD technique can also be achieved by accounting for water diffusion effects in the model (21). ASL-qBOLD technique for quantitative mapping of CMRO2 Combining qBOLD measurements of OEF with ASL measurements of CBF, allows quantitative mapping of tissue oxygen consumption CMRO2 – Eq. [1]. The method described in (22) is based on a GESSE sequence with arterial spin labeling (ASL) preparation pulses and is similar to previously used for studying water exchange in brain tissue (23).

MR Susceptometry-based CMRO2 quantification

Simultaneous estimation of oxygen saturation and cerebral blood flow in the major vessels draining and feeding the brain can be used for rapid non-invasive quantification of whole-brain CMRO2. The vessel of interest often includes internal jugular vein and/or superior sagittal sinus (SSS). The principle of the MR susceptometry of the whole brain is based on the measurement of the susceptibility difference between blood in the draining vein (such as jugular vein or SSS), and its surrounding tissue by measuring the phase difference with a GRE sequence (field mapping) (24-28). The SSS is often preferred over the internal jugular vein where severe susceptibility artifacts, caused by the proximity of air spaces such as the oral cavity and trachea, may complicate measurements. An additional benefit of the SSS is the elimination of contamination by the blood from extra-cranial sources (29).

T2-based CMRO2 quantification

Another approach for quantifying biological tissue hemodynamic properties is based on measuring blood T2 relaxation that is related to blood oxygenation level. In (30), CPMG pulse sequence was used to measure the blood transverse relaxation rate constant. Lu et al (31) proposed a spin-labeling technique, TRUST (T2-Relaxation-Under-Spin-Tagging), which can isolate pure venous blood signal (see also (32)). TRUST technique minimizes the partial volume effect and avoids the need for judicious selection of voxels containing blood. The T2 relaxation time of the TRUST signal can then be determined and converted to venous oxygenation Yv using a calibration plot (33-35).

A direct measurement of CMRO₂ is also possible by using tracers such as ¹⁷O₂. This technique is described in detail in (36).

Acknowledgements

No acknowledgement found.

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Proc. Intl. Soc. Mag. Reson. Med. 24 (2016)