The interaction between magnetization transfer and blood‐oxygen‐level‐dependent effects

Abstract

Low-power off-resonance spin-echo magnetization transfer (MT) imaging experiments with a long repetition time (TR) were performed on rat brain for a range of arterial PCO 2 levels. The measured magnetization transfer ratio decreased with increased arterial PCO 2 levels. When performing blood-oxygenlevel-dependent (BOLD) functional magnetic resonance imaging (fMRI)-type data analysis in which signal intensities were normalized to the normocapnic state, the CO 2 -based BOLD effect was much stronger with than without saturation. This increased effect is a consequence of the fact that the MT effect reduces the signal intensity in tissue more than in blood, thereby amplifying the contribution of the intravascular BOLD signal change to the overall BOLD effect. The results offer a potential approach to measure absolute cerebral blood volume in vivo and to amplify the BOLD effects for fMRI studies. Magnetization transfer (MT) in biologic tissues is a commonly employed magnetic resonance imaging (MRI) contrast parameter (1). It provides a unique method of tissue characterization reflecting interaction between the solidlike macromolecular lattice and cellular water (2,3). The magnitude of MT is usually described by the so-called magnetization transfer ratio (MTR). Quantitatively, (1 Ϫ MTR) is equal to the ratio of signal intensities with and without off-resonance irradiation. It is well known (4) that MTR depends on various tissue water parameters (spin density, magnetization exchange rates, T 1 , T 2 , etc.) and experimental parameters (saturation scheme, saturation power, spectral width, frequency offset, etc.). However, it is still controversial as to how MTR changes during physiologic perturbations such as hypercapnia, hypoxia, and neural activation (5-8). In human functional magnetic resonance imaging (fMRI) studies using gradient echo (GRE) echo-planar imaging (EPI) at 1.5 T, Song et al. (5) observed that the use of off-resonance radiofrequency (RF) irradiation is capable of creating an enhancement in the contrast of the blood-oxygenation-level-dependent (BOLD) effect (9,10). Zhang et al. (6) found that MT weighting resulted in a reduction of both the activated area and the fMRI signal, corresponding to an increase in MTR during task activation. We recently (8) found that MTR is reduced under hypercapnia, but increases following cardiac arrest and focal ischemia in the rat brain using spin-echo (SE) EPI at 4.7 T. Some of these experimental observations seem contradictory and a better understanding of the effect is needed.The purpose of this study was to quantify the MTR changes in the brain as a function of arterial PCO 2 level and to use this dependence to study the interaction between the BOLD and MT effects in the parenchyma. Parenchyma is composed of microvessels and extravascular tissue (11,12). The microvasculature consists of arterioles, capillaries, and venules, which determine the total cerebral blood volume (CBV), i.e., CBV ϭ i CBV i , in which i ϭ a, c, and v corresponding to arteriolar, capillary, and ve...

The BOLD post-stimulus undershoot, one of the most debated issues in fMRI

“…Their method can be used at high field MRI, where venous blood is invisible due to short T2*. When removing tissue signal (as much as up to 60%) using magnetization transfer (MT) weighting, CBV a can be derived using the knowledge that blood is not affected when irradiating sufficiently off-resonance (Hua et al, 2009; Wolff and Balaban, 1989; Zhou et al, 2005). They did not separate out capillary effects, but mention that part of the early capillaries are included in their CBV a .…”

Functional MRI with magnetization transfer effects: Determination of BOLD and arterial blood volume changes

“…Initially, human neural activation studies found that MT reduced the BOLD percentage signal change for most activated pixels, and that MTR increased with task activation (5). In contrast, recent hypercapnia studies in rat found that MT increased the BOLD percentage signal change, and that MTR decreased with arterial partial pressure of CO 2 (PACO 2 ) levels (6). Further studies are necessary to understand BOLD signals with MT effects.…”

“…Signal intensity measurements with vs. without off‐resonance irradiation give the MT attenuation factor (1 – MTR), where MTR is the MT ratio, which accounts for both MT (spin exchange and cross relaxation) and any potential direct saturation effects of the off‐resonance pulse (3). Functional blood‐oxygenation‐level–dependent (BOLD) studies incorporating off‐resonance spin preparation have examined the effects on functional MRI (fMRI) contrast (4–6). Initially, human neural activation studies found that MT reduced the BOLD percentage signal change for most activated pixels, and that MTR increased with task activation (5).…”

Quantitative measurement of cerebral blood volume using velocity‐selective pulse trains

“…Spatially-selective ASL techniques with multiple labeling delays have been developed to estimate the arterial cerebral blood volume (29,30). Other approaches are to combine ASL with magnetization transfer effects (31,32) or to use the inflow-based Vascular-space-occupancy (VASO) MRI (33,34). A sophisticated T 2 * -based relaxation model has also been proposed for measuring venous cerebral blood volume (35).…”