Functional connectivity in blood oxygenation level‐dependent and cerebral blood volume‐weighted resting state functional magnetic resonance imaging in the rat brain

Purpose:

To directly compare functional connectivity and spatiotemporal dynamics acquired with blood oxygenation level‐dependent (BOLD) and cerebral blood volume (CBV)‐weighted functional magnetic resonance imaging (fMRI) in anesthetized rats.

Materials and Methods:

A series of BOLD images were acquired in 10 rats followed by CBV‐weighted images created by injection of ultrasmall iron oxide particles. Functional connectivity, spectral information, and spatiotemporal dynamics were compared for the BOLD and CBV‐weighted resting state scans.

Results:

BOLD scans exhibited higher cross‐correlation values compared to CBV‐weighted scans, but the spatial patterns of correlation were similar. The BOLD spectrum contains power evenly distributed throughout the low‐frequency range while the CBV power spectrum exhibited a high power peak localized to ≈0.2 Hz. Both BOLD and CBV resting state scans showed similar propagating waves of activity along the cortex from the SII toward MI; however, these waves were detected more often in BOLD scans than in CBV scans.

Conclusion:

While the power spectrum of the CBV signal is different from that of the BOLD signal, both connectivity maps and spatiotemporal dynamics are similar for the two modalities. Further experiments should address the relationship between spontaneous neural activity, local changes in metabolism, and hemodynamic fluctuations to elucidate the origins of the BOLD and CBV signals. J. Magn. Reson. Imaging 2010;32:584–592. © 2010 Wiley‐Liss, Inc.     

Detection of acute renal ischemia in swine using blood oxygen level-dependent magnetic resonance imaging

PURPOSE: To determine the feasibility and sensitivity of blood oxygen level-dependent (BOLD) magnetic resonance imaging (MRI) to detect acute renal ischemia, using a swine model, and to present the causes of variability and assess techniques that minimize variability introduced during data analysis. MATERIALS AND METHODS: BOLD MRI was performed in axial and coronal planes of the kidneys of five swine. Color R2* maps were calculated and mean R2* values and 95% confidence intervals (CIs) for the cortex and medulla were determined for baseline, renal artery occlusion and reperfusion conditions. Paired Student's t-tests were used to determine significance. RESULTS: Mean R2* measurements increased from baseline during renal artery occlusion in the cortex (axial, 13.8-24.6 second(-1); coronal, 14.4-24.7 second(-1)) and medulla (axial, 19.3-32.2 second(-1); coronal, 20.1-30.7 second(-1)). These differences were significant for both the cortex (axial, P < 0.04; coronal, P < 0.005) and medulla (axial, P < 0.02; coronal, P < 0.0005). No significant change was observed in the contralateral kidney. CONCLUSION: R2* values were significantly higher than baseline for medulla and cortex during renal artery occlusion. More variability exists in R2* measurements in the medulla than the cortex and in the axial than the coronal plane.     

Simultaneous MRI acquisition of blood volume, blood flow, and blood oxygenation information during brain activation.

Simultaneous acquisition of complementary functional hemodynamic indices reflecting different aspects of brain activity would be a valuable tool for functional brain-imaging studies offering enhanced detection power and improved data interpretation. As such, a new MRI technique is presented that is able to achieve concurrent acquisition of three hemodynamic images based primarily on the changes of cerebral blood volume, blood flow, and blood oxygenation, respectively, associated with brain activation. Specifically, an inversion recovery pulse sequence has been designed to measure VASO (vascular space occupancy), ASL (arterial spin labeling) perfusion, and BOLD (blood-oxygenation-level-dependent) signals in a single scan. The MR signal characteristics in this sequence were analyzed, and image parameters were optimized for the simultaneous acquisition of these functional images. The feasibility and efficacy of the new technique were assessed by brain activation experiments with visual stimulation paradigms. Experiments on healthy volunteers showed that this technique provided efficient image acquisition, and thus higher contrast-to-noise ratio per unit time, compared with conventional techniques collecting these functional images separately. In addition, it was demonstrated that the proposed technique was able to be utilized in event-related functional MRI experiments, with potential advantages of obtaining accurate transient information of the activation-induced hemodynamic responses.     

Nonnvasive assessment of vascular architecture and function during modulated blood oxygenation using susceptibility weighted magnetic resonance imaging.

Susceptibility weighted imaging (SWI) is a BOLD-sensitive method for visualizing anatomical features such as small cerebral veins in high detail. The purpose of this study was to evaluate high-resolution SWI in combination with a modulation of blood oxygenation by breathing of air, carbogen, and oxygen and to directly visualize the effects of changing blood oxygenation on the magnetic field inside and around venous blood vessels. Signal changes associated with the response to carbogen and oxygen breathing were evaluated in different anatomic regions in healthy volunteers and in two patients with brain tumors. In the magnitude images inhalation of carbogen led to significant signal intensity changes ranging from +4.4 +/- 1.9% to +9.5 +/- 1.4% in gray matter and no significant changes in thalamus, putamen, and white matter. During oxygen breathing mean signal changes were smaller than during carbogen breathing. The method is capable of producing high-resolution functional maps of BOLD response to carbogen and oxygen breathing as well as high-resolution images of venous vasculature. Its sensitivity to changes in blood oxygenation was demonstrated by in vivo visualization of the BOLD effect via phase imaging.     

Functional imaging of the parotid glands using blood oxygenation level dependent (BOLD)-MRI at 1.5T and 3T

PURPOSE: To evaluate the function of the parotid glands before and during gustatory stimulation, using an intrinsic susceptibility-weighted MRI method (blood oxygenation level dependent, BOLD-MRI) at 1.5T and 3T. MATERIALS AND METHODS: A total of 10 and 13 volunteers were investigated at 1.5T and 3T, respectively. Measurements were performed before and during gustatory stimulation using ascorbate. Circular regions of interest (ROIs) were delineated in the left and right parotid glands, and in the masseter muscle for comparison. The effects of stimulation were evaluated by calculating the difference between the relaxation rates, DeltaR(2)*. Baseline and stimulation were statistically compared (Student's t-tests), merging both parotid glands. RESULTS: The averaged DeltaR(2)* values prestimulation obtained in all parotid glands were stable (-0.61 to 0.38 x 10(-3) seconds(-1)). At 3T, these values were characterized by an initial drop (to -2.7 x 10(-3) seconds(-1)) followed by a progressive increase toward the baseline. No significant difference was observed between baseline and parotid gland stimulation at 1.5T, neither for the masseter muscle at both field strengths. A considerable interindividual variability (over 76%) was noticed at both magnetic fields. CONCLUSION: BOLD-MRI at 3T was able to detect DeltaR(2)* changes in the parotid glands during gustatory stimulation, consistent with an increase in oxygen consumption during saliva production.     

Comparison of the BOLD- and EPISTAR-technique for functional brain imaging by using signal detection theory

Two magnetic resonance imaging techniques, BOLD (blood oxygenation level dependent) and EPISTAR (echo-planar imaging and signal targeting with alternating radio-frequency), were compared for functional brain imaging. Ten volunteers were imaged performing a sequential finger to thumb opposition task alternating with no movement conditions. Techniques were compared using variance maps and signal detection theory (ROC analysis). True positive activation in regions of interest with expected task-dependent signal changes were computed versus false activation rates in regions in which no activation was expected. D-prime coefficients were calculated for each comparison and statistically compared using a paired t test. Activation in the perirolandic region was seen in all volunteers with both techniques. There was no significant difference for the d-prime between BOLD and EPISTAR. These results indicate that based on a different physiologic principle, EPISTAR is an alternative to BOLD to perform fMRI with similar results.     

Application of sensitivity-encoded echo-planar imaging for blood oxygen level-dependent functional brain imaging.

The benefits of sensitivity-encoded (SENSE) echo-planar imaging (EPI) for functional MRI (fMRI) based on blood oxygen level-dependent (BOLD) contrast were quantitatively investigated at 1.5 T. For experiments with 3.4 x 3.4 x 4.0 mm(3) resolution, SENSE allowed the single-shot EPI image acquisition duration to be shortened from 24.1 to 12.4 ms, resulting in a reduced sensitivity to geometric distortions and T(*)(2) blurring. Finger-tapping fMRI experiments, performed on eight normal volunteers, showed an overall 18% loss in t-score in the activated area, which was substantially smaller than expected based on the image signal-to-noise ratio (SNR) and g-factor, but similar to the loss predicted by a model that takes physiologic noise into account.     

Detection of brain activation using oxygenation sensitive functional spectroscopy

A nonwater-suppressed localized spectroscopy experiment using the PRESS-sequence has been used to study the signal changes of the water resonance during cortical activation. Significant effects with an effect-to-noise ratio up to 50:1 for a single shot experiment have been observed upon photic stimulation. The exceedingly high signal-to-noise ratio of the experiment was used to demonstrate signal changes as low as 0.1% after electrical stimulation of the median nerve.     

Three-year follow-up of human transplanted kidneys by diffusion-weighted MRI and blood oxygenation level-dependent imaging

Purpose:

To prospectively determine the 3‐year stability and potential changes of functional parameters in renal allograft recipients obtained from diffusion‐weighted imaging (DWI) and blood oxygenation level‐dependent (BOLD) MRI.

Materials and Methods:

Nine renal allograft recipients underwent DWI and BOLD‐MRI twice, once 7 ± 3 months after transplantation, and again 32 ± 2 months after the first MRI. DWI yielded an apparent diffusion coefficient (ADC) and the perfusion contribution (F_P). BOLD imaging yielded R2*, providing an estimation of renal oxygenation. Coefficients of variation between (CV_b) and within subjects (CV_w) were calculated.

Results:

The parameters were stable after 32 months in eight of the nine patients, who had well‐functioning allografts. Mean diffusion values were very similar in the first and second scan. CV_w and CV_b for ADC values were less than 3.5% and 5.9%, respectively, in cortex and medulla, but were higher for F_P (15%–18%). CV_w and CV_b of R2* were also low (medulla: CV_w = 10.8%, CV_b = 11.4%; cortex: CV_w and CV_b = 7.2%). R2* increased significantly (P = 0.035) in cortex but not in medulla, suggesting reduced cortical oxygen content. One subject with decreased glomerular filtration rate demonstrated strongly altered parameters.

Conclusion:

In the absence of graft dysfunction, DWI and BOLD imaging yield consistent results over 3 years in stable human renal allograft recipients. J. Magn. Reson. Imaging 2012;35:1133‐1138. © 2011 Wiley Periodicals, Inc.     

Evaluation of intrarenal oxygenation by BOLD MRI at 3.0 T

PURPOSE: To examine the benefit of using higher field strengths for BOLD MRI to detect changes in renal medullary oxygenation following pharmacological maneuvers. MATERIALS AND METHODS: Renal BOLD MRI, primarily at 1.5 T, has been shown to be useful for monitoring changes in medullary oxygenation status. We performed the present studies on a 3.0 T scanner using a multiple gradient-echo (mGRE) sequence with a multicoil array to acquire 16 T2*-weighted images within a single breath-hold. Data were obtained before and after administration of furosemide (20 mg iv). RESULTS: The baseline renal R2* (mean +/- SE) at 3.0 T was 37.4+/-1.2 Hz in the medulla, and 21.8 +/- 1.2 Hz in the cortex. The BOLD response to furosemide (DeltaR2*) at 3.0 T was 11.8 +/- 1.1 Hz in the medulla, and 3.0 +/- 0.5 Hz in the cortex. CONCLUSION: Higher magnetic field strength is beneficial for renal BOLD MRI studies. The cortico-medullary contrast on the R2* map was significantly improved at 3.0 T, with no evidence of increased bulk susceptibility artifacts. Baseline R2* and DeltaR2* in the renal medulla at 3.0 T were both significantly higher compared to our previously reported data obtained at 1.5 T.     

Assessment of early renal allograft dysfunction with blood oxygenation level-dependent MRI and diffusion-weighted imaging

PurposeTo investigate blood oxygenation level-dependent (BOLD) MRI and diffusion-weighted imaging (DWI) at 3 T for assessment of early renal allograft dysfunction.Materials and methods34 patients with a renal allograft (early dysfunction, 24; normal, 10) were prospectively enrolled. BOLD MRI and DWI were performed at 3 T. R2* and apparent diffusion coefficient (ADC) values were measured in cortex and medulla of the allografts. Correlation between R2* or ADC values and estimated glomerular filtration rate (eGFR) was investigated. R2* or ADC values were compared among acute rejection (AR), acute tubular necrosis (ATN) and normal function.ResultsIn all renal allografts, cortical or medullary R2* and ADC values were moderately correlated with eGFR (P < 0.05). Early dysfunction group showed lower R2* and ADC values than normal function group (P < 0.05). AR or ATN had lower R2* values than normal allografts (P < 0.05), and ARs had lower cortical ADC values than normal allografts (P < 0.05). No significant difference of R2* or ADC values was found between AR and ATN (P > 0.05).ConclusionBOLD MRI and DWI at 3 T may demonstrate early functional state of renal allografts, but may be limited in characterizing a cause of early renal allograft dysfunction. Further studies are needed.     

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.     

MR perfusion, diffusion and BOLD imaging of methotrexate-exposed swine brain

PURPOSE: To evaluate the methotrexate (MTX)-exposed swine brain, functional magnetic resonance imaging (MRI), including perfusion, diffusion, and blood-oxygen-level-dependent (BOLD) contrast imaging, was used. MATERIAL AND METHODS: Juvenile pigs received either 2 x 5 g/m(2), or 5 x 2 g/m(2) MTX intravenously within one month. MRI was performed (sedative: propofol) before (14-17 kg, N = 6) and after (21-27 kg, N = 4) the MTX exposure. Also, age-matched controls (22-27 kg, N = 4) were imaged. RESULTS: After the MTX exposure, reduced (from 2%-4% to 0%-1%) or negative (-2% to -3%) BOLD responses were detected; apparent diffusion coefficient (ADC) or relative perfusion values did not change. CONCLUSION: This study suggests that MTX-related changes in the brain may be detected as changes in flow-metabolism coupling as reduced or negative response (for somatosensory activation) in the BOLD contrast MRI. The contrast agent perfusion MRI, without absolute quantification, may not show global damage in brain perfusion related to the MTX exposure in the swine model used. ADC (in one direction) may not indicate MTX-related changes in the brain.     

Evaluation of intrarenal oxygenation in mice by BOLD MRI on a 3.0T human whole-body scanner

PURPOSE: To extend observations on intra-renal oxygenation with blood oxygen level-dependent (BOLD) MRI in human and rats to mouse kidneys imaged with a human whole-body scanner. MATERIALS AND METHODS: Renal BOLD MRI studies were performed on a 3.0T scanner using a multiple gradient-echo (mGRE) sequence with a custom-designed 2.0-cm surface coil to acquire six T(2)*-weighted images in mice (N = 8) at an in-plane resolution of 156 x 156 mum(2). BOLD MRI data were obtained before and after administration of furosemide (10 mg/kg intravenously [i.v.]). RESULTS: The mean weight of eight mice was 24.6 +/- 1.0 g. The baseline renal R(2)* (mean +/- standard error [SE]) was 28.6 +/- 2.1 seconds(-1) in the renal cortex (CO), 35.4 +/- 2.2 in the outer medulla (OM), and 21.2 +/- 2.1 seconds(-1) in the inner medulla (IM). The BOLD response to furosemide (DeltaR(2)*) was 4.1 +/- 1.4 in the CO, 10.1 +/- 2.1 seconds(-1) in the OM, and 3.4 +/- 0.8 seconds(-1) in the IM in mice. CONCLUSION: Intrarenal BOLD MR images with sufficiently high resolution can be obtained on a human whole-body scanner when combined with a small receiver coil to allow studies in mice. Both baseline R(2)* and DeltaR(2)* values following administration of furosemide were consistent with previous experience in humans and rats.     

Breath-hold R2* mapping with a multiple gradient-recalled echo sequence: Application to the evaluation of intrarenal oxygenation

Blood oxygenation level dependent (BOLD) MRI is sensitive to changes in regional oxygen supply versus demand and is therefore potentially useful in evaluating susceptibility to ischemic injury. Recently, we have demonstrated the use of BOLD MRI to evaluate intrarenal oxygenation using single shot echo-planar imaging (EPI). Here, we present an alternate implementation of BOLD MRI sequence, using multiple gradient echoes, that does not require any specialized hardware.     

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.     

Complex relationship between changes in oxygenation status and changes in R*2: the case of insulin and NS-398, two inhibitors of oxygen consumption.

Insulin and NS-398 have been reported to inhibit oxygen consumption in experimental tumor models, thereby increasing oxygenation and radiosensitization. The aim of this work was to use MRI to study changes in murine FSaII tumor hemodynamics after administration of those oxygen consumption inhibitors. A multiple-echo gradient-echo (GRE) MRI sequence (4.7 T) was used to map changes in three factors: the GRE signal (at TE=20 ms), the parameter S0 (theoretical signal at TE=0 ms), and the relaxation rate R*2. Perfusion maps were obtained by dynamic contrast-enhanced (DCE) MRI. Insulin caused a significant decrease in the tumor blood oxygen level-dependent (BOLD) signal over time. factor This was likely the result of decreased blood flow, since both S0 and the percentage of perfused tumor decreased as well. Tumor R*2 did not change significantly in response to the treatments, which is surprising considering that other non-MRI techniques (electron paramagnetic resonance (EPR) oximetry and fiber-optic probes) have shown that tumor oxygenation increases after treatment. This suggests that metabolic changes associated with vasoactive challenges may have an unpredictable influence on blood saturation and R*2. In conclusion, this study further emphasizes the fact that changes in BOLD signal and R*2 in tumors do not depend uniquely on changes in oxygenation status.     

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.