Anatomical,blood oxygenation level‐dependent,and blood flow MRI of nonhuman primate (baboon) retina

The goal of this study was to demonstrate high‐resolution anatomical, blood oxygenation level‐dependent, and blood flow MRI on large nonhuman primate retinas using a 3‐Tesla clinical scanner as a first step toward translation. Baboon was chosen because of its evolutionary similarity to human. Anesthetized preparation, free of eye‐movement artifacts, was used to evaluate clinical scanner hardware feasibility and optimize multimodal protocols for retinal MRI. Anatomical MRI (0.1 × 0.2 × 2.0 mm³) before contrast‐agent injection detected three alternating bright–dark–bright layers. The hyperintense inner strip nearest to the vitreous was enhanced by an intravascular contrast agent, which likely included the ganglion and bipolar cell layer and the embedded retinal vessels. The hypointense middle strip showed no contrast enhancement, which likely included the avascular outer unclear layer and photoreceptor segments. The hyperintense outer strip showed contrast enhancement, which likely corresponded to the choroid vascular layer. In the posterior retina, the total thickness including the choroid was 617 ± 101 μm (± standard deviation, n = 7). Blood oxygenation level‐dependent functional MRI (0.3 × 0.6 × 2.0 mm³) of oxygen inhalation relative to air increased the signals by 6.5 ± 1.4%. Basal blood flow (2 × 2 × 2 mm³) was 83 ± 30 mL/100 g/min (air), and hypercapnia increased blood flow by 25 ± 9% (P < 0.05). This study demonstrates multimodal MRI to image anatomy, physiology, and function on large nonhuman primate retinas using a clinical scanner, offering encouraging data to explore human applications. Magn Reson Med, 2011. © 2011 Wiley‐Liss, Inc.     

Measuring brain oxygenation in humans using a multiparametric quantitative blood oxygenation level dependent MRI approach

Quantitative blood oxygenation level dependent approaches have been designed to obtain quantitative oxygenation information using MRI. A mathematical model is usually fitted to the time signal decay of a gradient‐echo and spin‐echo measurements to derive hemodynamic parameters such as the blood oxygen saturation or the cerebral blood volume. Although the results in rats and human brain have been encouraging, recent studies have pointed out the need for independent estimation of one or more variables to increase the accuracy of the method. In this study, a multiparametric quantitative blood oxygenation level dependent approach is proposed. A combination of arterial spin labeling and dynamic susceptibility contrast methods were used to obtain quantitative estimates of cerebral blood volume and cerebral blood flow. These results were combined with T and T₂ measurements to derive maps of blood oxygen saturation or cerebral metabolic rate of oxygen. In 12 normal subjects, a mean cerebral blood volume of 4.33 ± 0.7%, cerebral blood flow of 43.8 ± 5.7 mL/min/100 g, blood oxygen saturation of 60 ± 6% and cerebral metabolic rate of oxygen 157 ± 23 μmol/100 g/min were found, which are in agreement with literature values. The results obtained in this study suggest that this methodology could be applied to study brain hypoxia in the setting of pathology. Magn Reson Med, 2012. © 2011 Wiley Periodicals, Inc.     

Comparison of 1H blood oxygen level–dependent (BOLD) and 19F MRI to investigate tumor oxygenation

Fluorine‐19 [¹⁹F] MRI oximetry and ¹H blood oxygen level–dependent (BOLD) MRI were used to investigate tumor oxygenation in rat breast 13762NF carcinomas, and correlations between the techniques were examined. A range of tissue oxygen partial pressure (pO₂) values was found in the nine tumors while the anesthetized rats breathed air, with individual tumor pO₂ ranging from a mean of 1 to 36 torr and hypoxic fraction (HF10) (<10 torr) ranging from 0% to 75%, indicating a large intra‐ and intertumor heterogeneity. Breathing oxygen produced significant increase in tumor pO₂ (mean ΔpO₂ = 50 torr) and decrease in HF₁₀ (P < 0.01). ¹H BOLD MRI observed using a spin echo‐planar imaging (EPI) sequence revealed a heterogeneous response and significant increase in mean tumor signal intensity (SI) (ΔSI = 7%, P < 0.01). R measured by multigradient‐echo (MGRE) MRI decreased significantly in response to oxygen (mean ΔR = ?4 s^?1; P < 0.05). A significant correlation was found between changes in mean tumor pO₂ and mean EPI BOLD ΔSI accompanying oxygen breathing (r² > 0.7, P < 0.001). Our results suggest that BOLD MRI provides information about tumor oxygenation and may be useful to predict pO₂ changes accompanying interventions. Significantly, the magnitude of the BOLD response appears to be predictive for residual tumor HFs. Magn Reson Med, 2009. © 2009 Wiley‐Liss, Inc.     

Breathhold‐regulated blood oxygenation level‐dependent (BOLD) MRI of human brain at 3 tesla

Purpose:

To investigate the cerebrovascular response to repeated breathhold challenges using blood oxygenation level‐dependent (BOLD) MRI at 3T and compare the results with previous data at 1.5T.

Materials and Methods:

Six normal volunteers and six patients with brain tumors were recruited for this 3T study. For the normal group, BOLD MRI during repeated breathholds of different durations (five to 30 seconds) were acquired. Maximum signal change, full‐width at half‐maximum (FWHM) and onset time (defined as the time to the first half‐maximum) were determined by curve fitting. The fractional activation volume was also calculated. Patients performed a 10‐ or 15‐second breathhold paradigm according to individual capability.

Results:

Significant BOLD signal increases in the gray matter for a breathhold period as short as 5 seconds at 3T, instead of 10 seconds at 1.5T. The fractional activation volume vs. breathhold duration reached a plateau of 49.54 ± 7.26% at 15 seconds at 3T, which was higher and shorter than that at 1.5T. The maximum signal changes were significantly larger (a 69% increase) at 3T than at 1.5T. In the patient group, there were BOLD signal increases in gray matter but not in tumor bulk or perifocal edema, which agreed with the results previously found at 1.5T.

Conclusion:

BOLD MRI at 3T is more sensitive for detecting breathhold‐regulated signal changes than at 1.5T, which allows a shorter and more feasible breathhold paradigm for clinical applications in patients with brain tumors. J. Magn. Reson. Imaging 2010;31:78–84. © 2009 Wiley‐Liss, Inc.     

Anesthetic effects on regional CBF,BOLD, and the coupling between task‐induced changes in CBF and BOLD: An fMRI study in normal human subjects

Functional MR imaging was performed in sixteen healthy human subjects measuring both regional cerebral blood flow (CBF) and blood oxygen level dependent (BOLD) signal when visual and auditory stimuli were presented to subjects in the presence or absence of anesthesia. During anesthesia, 0.25 mean alveolar concentration (MAC) sevoflurane was administrated. We found that low‐dose sevoflurane decreased the task‐induced changes in both BOLD and CBF. Within the visual and auditory regions of interest inspected, both baseline CBF and the task‐induced changes in CBF decreased significantly during anesthesia. Low‐dose sevoflurane significantly altered the task‐induced CBF‐BOLD coupling; for a unit change of CBF, a larger change in BOLD was observed in the anesthesia condition than in the anesthesia‐free condition. Low‐dose sevoflurane was also found to have significant impact on the spatial nonuniformity of the task‐induced coupling. The alteration of task‐induced CBF‐BOLD coupling by low‐dose sevoflurane introduces ambiguity to the direct interpretation of functional MRI (fMRI) data based on only one of the indirect measures—CBF or BOLD. Our observations also indicate that the manipulation of the brain with an anesthetic agent complicates the model‐based quantitative interpretation of fMRI data, in which the relative task‐induced changes in oxidative metabolism are calculated by means of a calibrated model given the relative changes in the indirect vascular measures, usually CBF and BOLD. Magn Reson Med 60:987–996, 2008. © 2008 Wiley‐Liss, Inc.     

Physiological origin of low‐frequency drift in blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI)

We investigated the biophysical mechanism of low‐frequency drift in blood‐oxygen‐level‐dependent (BOLD) functional magnetic resonance imaging (fMRI) (0.00–0.01 Hz), by exploring its spatial distribution, dependence on imaging parameters, and relationship with task‐induced brain activation. Cardiac and respiratory signals were concurrently recorded during MRI scanning and subsequently removed from MRI data. It was found that the spatial distribution of low‐frequency drifts in human brain followed a tissue‐specific pattern, with greater drift magnitude in the gray matter than in white matter. In gray matter, the dependence of drift magnitudes on TE was similar to that of task‐induced BOLD signal changes, i.e., the absolute drift magnitude reached the maximum when TE approached T whereas relative drift magnitude increased linearly with TE. By systematically varying the flip angle, it was found that drift magnitudes possessed a positive dependence on image intensity. In phantom experiments, the observed drift was not only much smaller than that of human brain, but also showed different dependence on TE and flip angle. In fMRI studies with visual stimulation, a strong positive correlation between drift effects at baseline and task‐induced BOLD signal changes was observed both across subjects and across activated pixels within individual participants. We further demonstrated that intrinsic, physiological drift effects are a major component of the spontaneous fluctuations of BOLD fMRI signal within the frequency range of 0.0–0.1 Hz. Our study supports brain physiology, as opposed to scanner instabilities or cardiac/respiratory pulsations, as the main source of low‐frequency drifts in BOLD fMRI. Magn Reson Med 61, 2009. © 2009 Wiley‐Liss, Inc.     

Extravascular proton-density changes as a non-BOLD component of contrast in fMRI of the human spinal cord.

The fractional signal intensity change (Delta S/S) observed during activation in T(2)-weighted fMRI of the spinal cord has previously been shown to depend linearly on the echo time (TE) but to have a positive value of roughly 2.5% extrapolated to zero TE. In this study we investigated the origin of this finding by measuring the Delta S/S in spinal fMRI with very short TEs. Our results demonstrate that the Delta S/S does not approach zero, but has a value as high as 3.3% at TE = 11 ms. At TEs > 33 ms we observed the linear relationship between Delta S/S and TE as in previous studies. These data demonstrate that there is a non-BOLD contribution to signal changes observed in spinal fMRI. We hypothesize that this contribution is a local proton density increase due to increased water exudation from capillaries with increased blood flow during neuronal activation, and term this effect "signal enhancement by extravascular protons" (SEEP).     

Blood oxygenation level-dependent (BOLD) MRI of human skeletal muscle at 1.5 and 3 T

Purpose:

To evaluate the dependence of skeletal muscle blood oxygenation level‐dependent (BOLD) effect and time course characteristics on magnetic field strength in healthy volunteers using an ischemia/reactive hyperemia paradigm.

Materials and Methods:

Two consecutive skeletal muscle BOLD magnetic resonance imaging (MRI) measurements in eight healthy volunteers were performed on 1.5 T and 3.0 T whole‐body MRI scanners. For both measurements a fat‐saturated multi‐shot multiecho gradient‐echo EPI sequence was applied. Temporary vascular occlusion was induced by suprasystolic cuff compression of the thigh. T2* time courses were obtained from two different calf muscles and characterized by typical curve parameters. Ischemia‐ and hyperemia‐induced changes in R2* (ΔR2*) were calculated for both muscles in each volunteer at the two field strengths.

Results:

Skeletal muscle BOLD changes are dependent on magnetic field strength as the ratio ΔR2*(3.0 T)/ΔR2*(1.5 T) was found to range between 1.6 and 2.2. Regarding time course characteristics, significantly higher relative T2* changes were found in both muscles at 3.0 T.

Conclusion:

The present study shows an approximately linear field strength dependence of ΔR2* in the skeletal muscle in response to ischemia and reactive hyperemia. Using higher magnetic fields is advisable for future BOLD imaging studies of peripheral limb pathologies. J. Magn. Reson. Imaging 2012;35:1227‐1232. © 2012 Wiley Periodicals, Inc.