Weili Lin

In vivo measurement of blood oxygen saturation using magnetic resonance imaging: A direct validation of the blood oxygen level-dependent concept in functional brain imaging

A novel noninvasive magnetic resonance imaging (MRI) method was developed to determine in vivo blood oxygen saturation and its changes during motor cortex activation in small cerebral veins. Specifically, based on susceptibility measurements in the resting states, pial veins were found to have a mean oxygen saturation of Yrest = 0.544 ± 0.029 averaged over 14 vessels in 5 volunteers. During activation, susceptibility measurements revealed an oxygen saturation change of ΔYsusc = 0.14 ± 0.02. Independent evaluation from blood flow velocity measurements yielded a value of ΔYflow = 0.14 ± 0.04 for this change. These results validate the blood oxygenation level‐dependent (BOLD) model in functional MRI (fMRI). Hum. Brain Mapping 5:341–346, 1997.

Artery and vein separation using susceptibility-dependent phase in contrast-enhanced MRA.

In magnetic resonance angiography, contrast agents are frequently used to help highlight arteries over background tissue. Unfortunately, enhancing veins hamper the visualization of arteries when data are collected over a long period of time after the arterial phase of the contrast agent. To overcome this problem, we have developed a novel imaging and postprocessing method that is capable of eliminating veins by utilizing the susceptibility difference between veins and surrounding tissue. This method was applied in the peripheral vasculature where the vessels are predominantly parallel to the main field and where the blood oxygen level‐dependent effect is most pronounced. Results are presented for both long (15.8 msec) and short echo times (7.8 msec) and for sequential and centrally reordered acquisition schemes. The short echo scan approach appears to be the most promising, making it possible to obtain good suppression of the venous signal even when the timing is not perfect or when repeat scans are necessary. J. Magn. Reson. Imaging 2000;12:661–670.

In vivo validation of the bold mechanism: A review of signal changes in gradient echo functional MRI in the presence of flow

Brain functional magnetic resonance imaging (FMRI) is possible because of local changes in blood flow and oxygenation levels. Understanding the role of each mechanism is important for interpreting FMRI results as well as for the design of the experiment itself. In this review, we address the role of flow and blood oxygen level dependence (BOLD) and how they can be used in conjunction with each other to enhance the BOLD effect. We also discuss the role of intra/extravascular signal changes in the presence of a vessel for the imaging situation and show how the ratio of these two contributions is likely to change as the blood volume fraction changes. Using the BOLD model itself, along with 3‐D phase imaging, we show that blood oxygenation level in veins in vivo is Y = 0.544 ± 0.029 as measured in 14 vessels in five subjects. Finally, we comment on the use of phase images themselves as a means to discriminate tissues with different levels of blood such as gray matter, white matter, and cerebrospinal fluid.

Magnetic resonance cerebral metabolic rate of oxygen utilization in hyperacute stroke patients

The purpose of this study was to explore the feasibility of obtaining magnetic resonance–measured cerebral metabolic rate of oxygen utilization (MR‐CMRO2) in acute ischemic stroke patients. Seven stroke patients were serially imaged: 4.5 ± 0.9 hours (tp1), 3 to 5 days (tp2), and 1 to 3 months (tp3) after symptom onset. Diffusion‐weighted, perfusion‐weighted, and multiecho gradient‐echo/spin‐echo images were acquired; cerebral blood flow and oxygen extraction fraction maps were obtained from which CMRO2 was calculated as the product of cerebral blood flow and oxygen extraction fraction. The final infarct lesions obtained from tp3 T2‐weighted images and the “penumbra” obtained from the tp1 perfusion‐weighted image–defined lesion were coregistered onto tp1 CMRO2 maps. CMRO2 values in the region of brain that eventually infarcted were reduced to 0.40 ± 0.24 of the respective region on the contralateral hemisphere. The “salvaged penumbra” defined by the area of mismatch between the final infarct and the tp1 perfusion‐weighted lesion demonstrated an average CMRO2 value of 0.55 ± 0.11 of the contralateral hemisphere. Although our results are preliminary and require further evaluation, the ability to obtain in vivo measurements of MR‐CMRO2 noninvasively potentially can provide information for determining brain tissue viability in acute ischemic stroke patients.

Regional cerebral blood volume: A comparison of the dynamic imaging and the steady state methods

Accurate assessment of regional cerebral blood volume (rCBV) is of critical importance in the study of cerebrovascular disease and other disorders of the central nervous system. Currently, magnetic resonance imaging (MRI) is able to measure rCBV non‐invasively with two commonly used methods: the dynamic imaging (DI) and steady state (SS) approaches. In this study, two questions were investigated. First, how do partial volume effects between gray matter (GM) and white matter (WM) and between epicortical vessels and brain parenchyma affect the estimation of rCBV when using the SS approach? Second, how comparable are the ratios of rCBV in GM to rCBV in WM (rCBV GM/WM) obtained with the two methods? We used a paramagnetic contrast agent, OPTIMARK (Mallinckrodt, St. Louis, MO), at a dose of 0.2 mmol/kg in anesthetized pigs (n = 6) to obtain rCBV maps using both methods. When a 10% rCBV threshold was used to minimize effects from large epicortical vessels, and tissue segmentation was used to separate GM from WM, rCBV values of 4.8 ± 0.3% and 3.3 ± 0.5% were obtained for GM and WM, respectively, with the SS approach. Significantly higher rCBV values for both GM (P < 0.001) and WM (P < 0.01) were observed when the contribution from large epicortical vessels was not removed. When tissue segmentation and rCBV thresholding were used on SS data, an rCBV GM/WM ratio of 1.5 ± 0.2 was obtained. This value did not differ significantly from the rCBV GM/WM ratio of 1.8 ± 0.6 obtained using the DI approach. J. Magn Reson. Imaging 1999;9:44–52

Improving High-Resolution MR Bold Venographic Imaging Using a T1 Reducing Contrast Agent

Recently, a new imaging method was proposed by Reichenbach et al (Radiology 1997;204:272–277) to image small cerebral venous vessels specifically. This method, referred to as high‐resolution blood oxygen level‐dependent venography (HRBV), relies on the susceptibility difference between the veins and the brain parenchyma. The resulting phase difference between the vessels and the brain parenchyma leads to signal losses over and above the usual T2* effect. At 1.5 T, a rather long TE (roughly 40 msec) is required for this cancellation to become significant, leading to enhanced susceptibility artifacts and a long data acquisition time. In this study, we examine the utility of incorporating a clinically available T1 reducing contrast agent, Omniscan (Sanofi Winthrop Pharmaceuticals, NY, NY), with the HRBV imaging approach to reduce susceptibility artifacts and imaging time while maintaining the visibility of cerebral veins. Using a double‐dose injection of Omniscan, we were able to reduce TE from 40 to 25 msec. This led to a decrease in TR from 57 to 42 msec, allowing a 26% reduction in data acquisition time while maintaining the visibility of cerebral venous vessels and reducing susceptibility artifacts. J. Magn. Reson. Imaging 1999;10:118–123, 1999.

Quantitative Magnetic Resonance Imaging in Experimental Hypercapnia: Improvement in the Relation between Changes in Brain R2* and the Oxygen Saturation of Venous Blood after Correction for Changes in Cerebral Blood Volume

Acute hypercapnia simultaneously induces increases in regional cerebral blood volume (rCBV) and the oxygen saturation of cerebral venous blood (Yv). Changes in both physiologic parameters may influence the changes in R2* (ΔR2*) that can be measured in the brain with gradient echo magnetic resonance imaging. The authors examined the effect of incorporating independent measurements of the change in rCBV (ΔrCBV) on the fidelity of the relation between ΔR2* and ΔYv in the setting of experimental hypercapnia. A two-dimensional T2*-weighted gradient echo sequence was used to measure ΔR2* in the brain parenchyma of anesthetized rats in response to hypercapnia with respect to the control state. In parallel, estimates of rCBV were obtained using a three-dimensional steady-state approach in conjunction with a paramagnetic contrast agent during both control and hypercapnic states so that a ΔrCBV could be calculated. Regional CBV values of 2.96 ± 0.82% and 5.74 ± 1.21% were obtained during the control and hypercapnic states, respectively, and linear relations between rCBV and CO2 tension in both arterial (r = 0.80) and jugular venous (r = 0.76) blood samples were obtained. When correlating ΔR2* directly with ΔYv, no clear relation was apparent, but a strong linear relation (r = 0.76) was observed when correction for ΔrCBV was incorporated into the data analysis. These results are consistent with the current understanding of the mechanisms of blood oxygen level–dependent (BOLD) contrast and underscore the potential importance of taking into account ΔrCBV when quantitative estimates of ΔYv from the “BOLD effect” are intended.

HEMISPHERIC LANGUAGE DOMINANCE IN CHILDREN DEMONSTRATED BY FUNCTIONAL MAGNETIC RESONANCE IMAGING

The objective of this study was to demonstrate hemispheric language dominance in normal children. Fifteen normal children were evaluated with functional magnetic resonance imaging (MRI) using an age-related silent word spelling paradigm. The data were analyzed with the cross-correlation method, and lateralization indices were calculated in language regions as determined by Talairach coordinates. Activation foci were detected in the left inferior frontal area and were strongly lateralized, with language lateralization indices of 0.74 ± 0.21 (age 7-12 years, nine subjects), and 0.79 ± 0.18 (13-18 years, six subjects). The indices were similar to those for adults (0.83 ± 0.21, four subjects). Our study established that language is strongly lateralized to the left hemisphere in children as young as 7 years of age. (J Child Neurol 1999;14:78-82).

Statistical assessment of crosscorrelation and variance methods and the importance of electrocardiogram gating in functional magnetic resonance imaging

Processing of functional magnetic resonance imaging (fMRI) data is a critical step in evaluating experimental results. We address the question of choosing between a Student t-test method, crosscorrelation method, or a weighted z-score method in analyzing functional MR images. We present an analytic analysis that makes it possible to make a statistical decision in setting the threshold for the crosscorrelation coefficient. Specifically, the theory for an receiver operating characteristic (ROC) analysis (description of type I and type II error) has been applied to the crosscorrelation method. Both theoretical predictions as well as model simulations are presented to prove that the crosscorrelation and weighted z-score method have the same statistical power. We introduce the concept of a variance image and use it to not only choose between the correlation image and a simple t-test image but also to obtain a final image that combines the efficient aspects of both the correlation and the simple t-test images. The variance image itself is shown to be an indicator of both patient motion and/or internal physiological motion in the brain. Furthermore, we delineate the importance of electrocardiogram (ECG) gating in reducing the variance in fMRI of human motor cortex.

Experimental Hypoxemic Hypoxia: Effects of Variation in Hematocrit on Magnetic Resonance T2*-Weighted Brain Images

T2*-weighted gradient echo magnetic resonance images of rat brain were obtained dynamically during acute hypoxemic hypoxia to investigate the relations between changes in cerebral blood oxygen saturation(ΔYb), blood hematocrit (Hct), and R2* (ΔR2*). Images from hypoxemic rats with normal Hct (42.8% ± 2.33%; n = 12) were compared with those from hypoxemic rats with mild (33.4% ± 1.88%; n = 8) or moderate (27.14% ± 2.7%; n = 10) reduction of Hct. A linear relation between ΔYb and ΔR2* was obtained for all three groups. However, the slopes of the linear regressions were statistically different from one another (P < 0.001), with the slopes of the regression lines increasing inversely with Hct; that is, the slope for normal Hct is less than the slope for mildly reduced Hct, which is less than the slope for moderately reduced Hct. These data suggest that for any given reduction in the oxygen saturation of cerebral blood, the ΔR2* will be of a lesser magnitude when the hemoglobin concentration is reduced; the data are consistent with existing theoretical models of deoxyhemoglobin content-dependent effects in T2*-weighted magnetic resonance imaging.