BOLD MRI response to hypercapnic hyperoxia in patients with meningiomas: correlation with Gadolinium-DTPA uptake rate

Because meningiomas tend to recur after (partial) surgical resection, radiotherapy is increasingly being applied for the treatment of these tumors. Radiation dose levels are limited, however, to avoid radiation damage to the surrounding normal tissue. The radiosensitivity of tumors can be improved by increasing tumor oxygen levels. The aim of this study was to investigate if breathing a hyperoxic hypercapnic gas mixture could improve the oxygenation of meningiomas. Blood oxygen level-dependent magnetic resonance imaging and dynamic Gadolinium (Gd)-DTPA contrast-enhanced MRI were used to assess changes in tumor blood oxygenation and vascularity, respectively. Ten meningioma patients were each studied twice; without and with breathing a gas mixture consisting of 2% CO(2) and 98% O(2). Values of T(2)* and the Gd-DTPA uptake rate k(ep) were calculated under both conditions. In six tumors a significant increase in the value of T(2)* in the tumor was found, suggesting an improved tumor blood oxygenation, which exceeded the effect in normal brain tissue. Contrarily, two tumors showed a significant T(2)* decrease. The change in T(2)* was found to correlate with both k(ep) and with the change in k(ep). The presence of both vascular effects and oxygenation effects and the heterogeneous response to hypercapnic hyperoxia necessitates individual assessment of the effects of breathing a hyperoxic hypercapnic gas mixture on meningiomas. Thus, the current MRI protocol may assist in radiation treatment selection for patients with meningiomas.     

Failure to direct detect magnetic field dephasing corresponding to ERP generation

Functional magnetic resonance imaging (fMRI) has become the method of choice for mapping brain activity in human subjects and detects changes in regional blood oxygenation and volume associated with local changes in neuronal activity. While imaging based on blood oxygenation level dependent (BOLD) contrast has good spatial resolution and sensitivity, the hemodynamic signal develops relatively slowly and is only indirectly related to neuronal activity. An alternative approach termed magnetic source magnetic resonance imaging (msMRI) is based on the premise that neural activity may be mapped by magnetic resonance imaging (MRI) with greater temporal resolution by detecting the local magnetic field perturbations associated with local neuronal electric currents. We used a hybrid ms/BOLD MRI method to investigate whether msMRI could detect signal changes that occur simultaneously at the time of the production of well-defined event-related potentials, the P300 and N170, in regions that previously have been identified as generators of these electrical signals. Robust BOLD activations occurred after some seconds, but we were unable to detect any significant changes in the T2*-weighted signal in these locations that correlated temporally with the timings of the evoked response potentials (ERPs).     

Effects of different levels of hypercapnic hyperoxia on tumour R(2)* and arterial blood gases

The hypercapnia induced by carbogen (95% O(2)/5% CO(2)) breathing, which is being re-evaluated as a clinical radiosensitiser, causes patient discomfort and hence poor compliance. Recent preclinical and clinical studies have indicated that the CO(2) content might be lowered without compromising increased tumour oxygenation and radiosensitisation. This preclinical study was designed to see if lower levels of hypercapnia could evoke similar decreases in the transverse relaxation rate R(2)* of rodent tumours to those seen with carbogen breathing. The response of rat GH3 prolactinomas to 1%, 212% and 5% CO(2) in oxygen, and 100% O(2) breathing, was monitored by non-invasive multi-gradient echo MRI to quantify R(2)*. As the oxygenation of haemoglobin is proportional to the blood p(a)O(2) and therefore in equilibrium with tissue pO(2), R(2)* is a sensitive indicator of tissue oxygenation. Hyperoxia alone decreased R(2)* by 13%, whilst all three hypercapnic hyperoxic gases decreased R(2)* by 29%. Breathing 1% CO(2) in oxygen evoked the same decrease in R(2)* as carbogen. The DeltaR(2)* response is primarily consistent with an increase in blood oxygenation, though localised increases in tumour blood flow were also identified in response to hypercapnia. The data support the concept that levels of hypercapnia can be reduced without loss of enhanced oxygenation and hence potential radiotherapeutic benefit.     

Initial attempts at directly detecting alpha wave activity in the brain using MRI

The “direct detection” of neuronal activity by MRI could offer improved spatial and temporal resolution compared to the blood oxygenation level-dependent (BOLD) effect. Here we describe initial attempts to use MRI to detect directly the neuronal currents resulting from spontaneous alpha wave activity, which have previously been shown to generate the largest extracranial magnetic fields. Experiments were successfully carried out on four subjects at 3 T. A single slice was imaged at a rate of 25 images per second under two conditions. The first (in darkness with eyes-closed) was chosen to promote alpha wave activity, while the second (eyes-open viewing a visual stimulus) was chosen to suppress it. The fluctuations of the phase and magnitude of the resulting MR image data were frequency analysed, and tested for the signature of both alpha wave activity and neuronal activity evoked by the visual stimulus.

Regions were found that consistently showed elevated power in fluctuations of the phase of the MR signal, in the frequency range of alpha waves, during the eyes-closed condition. It was conservatively assumed that if oscillations occurred at the same frequency in the magnitude signal from the same region or at the same frequency in the phase or magnitude signal from other regions overlying large vessels or cerebrospinal fluid (CSF), then the phase changes were not due to neuronal activity related to alpha waves. Using these criteria the data obtained were consistent with direct detection of alpha wave activity in three of the four volunteers. No significant MR signal fluctuations due to evoked activity were identified.     

Mapping of cerebrovascular reactivity using BOLD magnetic resonance imaging

Blood oxygen level-dependent (BOLD) contrast MRI is a simple non-invasive method of estimating "perfusion," and combined with a vasodilatory stimulus, may allow estimation of cerebral vascular reserve. We compared BOLD carbon dioxide (CO2) reactivity in the middle cerebral artery (MCA) perfusion territory to MCA flow velocity reactivity determined using transcranial Doppler ultrasound (TCD) in 16 patients with unilateral carotid artery stenosis or occlusion. Both BOLD and TCD reactivities were calculated from measurements acquired when the subjects were breathing air, and again when breathing a 6% CO2/air mixture, and were normalized by dividing by the difference in end tidal (ET) CO2. There was a significant correlation between interhemispheric MCA reactivity difference (contralateral-ipsilateral to the stenosis or occlusion) determined by BOLD MRI and TCD (r = 0.75, p < 0.001). In contrast, treating each hemisphere individually, there was no correlation between the absolute BOLD and TCD MCA CO2 reactivities (r = 0.08, p = 0.670). This appeared to be due to a variable BOLD signal change in the non-stenosed hemisphere between subjects, with little change in the normal hemisphere of a few subjects. In one patient, focal regions of reduced reactivity were seen in non-infarcted regions of the stenosed hemisphere, in the borderzones between arterial territories. BOLD reactivity maps provide information on the whole MCA territory reactivity, and may identify small regions of impaired reactivity which are not detected using TCD. However, BOLD reactivity maps only appear to provide semi-quantitative rather than quantitative data.     

Combination of BOLD-fMRI and VEP recordings for spin-echo MRI detection of primary magnetic effects caused by neuronal currents

In the present paper, for the first time, the feasibility to detect primary magnetic field changes caused by neuronal activity in vivo by spin-echo (SE) magnetic resonance imaging (MRI) is investigated. The detection of effects more directly linked to brain activity than secondary hemodynamic–metabolic changes would enable the study of brain function with improved specificity. However, the detection of neuronal currents by MRI is hampered by such accompanying hemodynamic changes. Therefore, SE image acquisition, rather than gradient-echo (GE) image acquisition, was preferred in the present work since the detection of primary neuronal and not blood oxygenation level-dependent (BOLD)-related effects may be facilitated by this approach. First of all, a precise spatiotemporal synchronization of image acquisition with the neuronal event had to be performed to avoid refocusing of the dephasing phenomenon during the course of the SE sequence. At this aim, we propose the combined use of visual evoked potential (VEP) recordings and BOLD-fMRI measurements prior to SE MRI scanning. Moreover, we exemplify by theory and experimentation how the control of artefactual signal changes due to BOLD and movement effects may be further improved by the experimental design. Finally, results from a pilot study using the proposed combination of VEP recordings and MRI techniques are reported, suggesting the feasibility of this method.     

A preliminary study of blood-oxygen-level-dependent MRI in patients with chronic kidney disease

Background

Blood-oxygen-level-dependent (BOLD) magnetic resonance imaging (MRI) can provide regional measurements of oxygen content using deoxyhemoglobin paramagnetic characteristics. The apparent relaxation rate or R2*(=1/T2*) can be determined from the slope of log (intensity) versus echo time and is directly proportional to the tissue content of deoxyhemoglobin. Thus, as the level of deoxyhemoglobin increases, T2* will decrease, leading to an increase in R2*. Chronic kidney disease (CKD) can affect oxygenation levels in renal parenchyma, which influences the clinical course of the disease. The goal of this study was to detect and assess renal oxygenation levels in CKD using BOLD MRI.

Methods

Fifteen healthy subjects and 11 patients with CKD underwent a renal scan using multigradient-recalled-echo sequence with eight echoes. R2* (1/s) of the renal cortex and medulla was measured on BOLD images. Of the 11 patients, nine had biopsy-proven chronic glomerulonephritis, and two had a similar diagnosis based on clinical symptoms and investigations.

Results

Mean medullary R2* (MR2*) and cortex R2* (CR2*) levels were significantly higher in patients (22 kidneys, MR2*=24.79±4.84 s⁻¹, CR2*=18.97±2.72 s⁻¹) than in controls (30 kidneys, MR2*=19.98±1.19 s⁻¹, CR2*=16.03±1.23 s⁻¹) (P<.01), and MR2* was increased more than CR2*. Medullary to cortical R2* ratios (MCR2*) of patients were significantly increased when compared with those of controls (P<.01). In the patient group, estimated glomerular filtration rate levels were greater than or equal to 60 ml/min/1.73 m² in six patients (12 kidneys), whose MR2* and CR2* were also significantly higher than those of controls (P<.01). Serum creatinine levels were normal in seven patients (14 kidneys), whose MR2*, CR2* and MCR2* were also higher than those of controls (P<.01).

Conclusions

BOLD MRI can be used to evaluate changes in renal oxygenation in CKD, suggesting that it has the potential to be an excellent noninvasive tool for the evaluation of renal function.     

Synchronized detection of minute electrical currents with MRI using Lorentz effect imaging

The blood oxygenation level-dependent (BOLD) effect is the most commonly used contrast mechanism in functional magnetic resonance imaging (fMRI), due to its relatively high spatial resolution and sensitivity. However, the ability of BOLD fMRI to accurately localize neuronal activation in space and time is limited by the inherent hemodynamic modulation. There is hence a need to develop alternative MRI methods that can directly image neuroelectric activity, thereby achieving both a high temporal resolution and spatial specificity as compared to conventional BOLD fMRI. In this paper, we extend the Lorentz effect imaging technique, which can detect spatially incoherent yet temporally synchronized minute electrical activity in a strong magnetic field, and demonstrate its feasibility for imaging randomly oriented electrical currents on the order of microamperes with a temporal resolution on the order of milliseconds in gel phantoms. This constitutes a promising step towards its application to direct imaging of neuroelectric activity in vivo, which has the same order of current density and temporal synchrony.     

In vivo hypoxia characterization using blood oxygen level dependent magnetic resonance imaging in a preclinical glioblastoma mouse model

PurposeHypoxia measurements can provide crucial information regarding tumor aggressiveness, however current preclinical approaches are limited. Blood oxygen level dependent (BOLD) Magnetic Resonance Imaging (MRI) has the potential to continuously monitor tumor pathophysiology (including hypoxia). The aim of this preliminary work was to develop and evaluate BOLD MRI followed by post-image analysis to identify regions of hypoxia in a murine glioblastoma (GBM) model.MethodsA murine orthotopic GBM model (GL261-luc2) was used and independent images were generated from multiple slices in four different mice. Image slices were randomized and split into training and validation cohorts. A 7 T MRI was used to acquire anatomical images using a fast-spin-echo (FSE) T2-weighted sequence. BOLD images were taken with a T2*-weighted gradient echo (GRE) and an oxygen challenge. Thirteen images were evaluated in a training cohort to develop the MRI sequence and optimize post-image analysis. An in-house MATLAB code was used to evaluate MR images and generate hypoxia maps for a range of thresholding and ΔT2* values, which were compared against respective pimonidazole sections to optimize image processing parameters. The remaining (n = 6) images were used as a validation group. Following imaging, mice were injected with pimonidazole and collected for immunohistochemistry (IHC). A test of correlation (Pearson's coefficient) and agreement (Bland-Altman plot) were conducted to evaluate the respective MRI slices and pimonidazole IHC sections.ResultsFor the training cohort, the optimized parameters of “thresholding” (20 ≤ T2* ≤ 35 ms) and ΔT2* (±4 ms) yielded a Pearson's correlation of 0.697. These parameters were applied to the validation cohort confirming a strong Pearson's correlation (0.749) when comparing the respective analyzed MR and pimonidazole images.ConclusionOur preliminary study supports the hypothesis that BOLD MRI is correlated with pimonidazole measurements of hypoxia in an orthotopic GBM mouse model. This technique has further potential to monitor hypoxia during tumor development and therapy.     

BOLD signal compartmentalization based on the apparent diffusion coefficient

Functional MRI (fMRI) can detect blood oxygenation level dependent (BOLD) hemodynamic responses secondary to neuronal activity. The most commonly used method for detecting fMRI signals is the gradient-echo echo-planar imaging (EPI) technique because of its sensitivity and speed. However, it is generally believed that a significant portion of these signals arises from large veins, with additional contribution from the capillaries and parenchyma. Early experiments using diffusion-weighted gradient-echo EPI have suggested that intra-voxel incoherent motion (IVIM) weighting inherent in the sequence can selectively attenuate contributions from different vessels based on the differences in the mobility of the blood within them. In the present study, we used similar approach to characterize the apparent diffusion coefficient (ADC) distribution within the activated areas of BOLD contrast. It is shown that the voxel values of the ADCs obtained from this technique can infer various vascular contributions to the BOLD signal.     

Visual cortex reactivity in sedated children examined with perfusion MRI (FAIR)

Sleeping and sedated children can respond to visual stimulation with a decrease in blood oxygenation level dependent (BOLD) functional MRI signal response. The contribution of metabolic and hemodynamic parameters to this inverse signal response is incompletely understood. It has been hypothesized that it is caused by a relatively greater increase of oxygen consumption compared to rCBF (regional cerebral blood flow) increase. We studied the rCBF changes during visual stimulation in four sedated children, aged 4-71 months, and four alert adults, with an arterial water spin labeling technique (FAIR) and BOLD fMRI in a 1.5T MR scanner. In the children, FAIR signal decreased by a mean of 0.96% (range 0.77-1.05) of the baseline periods of the non-selective images, while BOLD signal decreased by 2.03% (range 1.99-2.93). In the adults, FAIR and BOLD signal increased by 0.88% (range 0.8-0.99) and 2.63% (range 1.99-2.93), respectively. Thus, in the children, an rCBF increase could not be detected by perfusion MRI, but indications of a FAIR signal decrease were found. An rCBF decrease in the primary visual cortex during stimulation has not been reported previously, but it is a possible explanation for the negative BOLD response. Future studies will have to address if this response pattern is a consequence of age or sleep/sedation.     

Assessment of cerebrovascular reactivity with functional magnetic resonance imaging: comparison of CO(2) and breath holding

Cerebral blood flow (CBF) and oxygenation changes following both a simple breath holding test (BHT) and a CO(2) challenge can be detected with functional magnetic resonance imaging techniques. The BHT has the advantage of not requiring a source of CO(2) and acetazolamide and therefore it can easily be performed during a routine MR examination. In this study we compared global hemodynamic changes induced by breath holding and CO(2) inhalation with blood oxygenation level dependent (BOLD) and CBF sensitized fMRI techniques. During each vascular challenge BOLD and CBF signals were determined simultaneously with a combined BOLD and flow-sensitive alternating inversion recovery (FAIR) pulse sequence. There was a good correlation between the global BOLD signal intensity changes during breath holding and CO(2) inhalation supporting the notion that the BHT is equivalent to CO(2) inhalation in evaluating the hemodynamic reserve capacity with BOLD fMRI. In contrast, there was no correlation between relative CBF changes during both vascular challenges, which was probably due to the reduced temporal resolution of the combined BOLD and FAIR pulse sequence.     

超高场磁共振人体成像应用研究和医学前景

20世纪90年代初,随着第一代超高场磁共振成像仪的投入使用,因其诸多的优点,如更高的检测信噪比、更好的对比度、更强的BOLD效应和更宽的波谱,超高场磁共振成像成为国际医学磁共振领域最热门的研究方向之一.该文以最新一代的7.0 T MRI成像仪为例,简述超高场磁共振人体成像仪的系统结构、研究进展,并展望其在神经科学、认知科学和医学的应用前景.     

Increasing mean airway pressure reduces functional MRI (fMRI) signal in the primary visual cortex

Changes in both blood flow and blood oxygenation determine the functional MRI (fMRI) signal. In the present study factors responsible for blood oxygenation (e.g., FiO(2)) were held constant so that changes in pixel count would above all reflect changes in regional cerebral blood flow (rCBF). Continuous positive airway pressure (CPAP) breathing at 12 cm H(2)O, which was previously shown to influence rCBF, was applied in human volunteers (n = 19) to investigate the sensitivity of fMRI for changes in rCBF caused by increased mean airway pressure. Increasing the mean airway pressure decreased the pixel count in the primary visual cortex (median (range)): baseline: 219 (58-425) pixels vs. CPAP (12 cm H(2)O): 92 (0-262) pixels). These findings indicate that fMRI is sensitive to detect a reduced rCBF-response in the primary visual cortex. The underlying mechanism is likely to be a reduced basal rCBF due to constriction and/or compression of postcapillary venoles during CPAP breathing. These findings are important for interpreting fMRI results in awake and in artificially respirated patients, in whom positive airway pressure is used to improve pulmonary function during the diagnostic procedure.     

Retinotopic mapping with spin echo BOLD at 7T

For blood oxygenation level-dependent (BOLD) functional MRI experiments, contrast-to-noise ratio (CNR) increases with increasing field strength for both gradient echo (GE) and spin echo (SE) BOLD techniques. However, susceptibility artifacts and nonuniform coil sensitivity profiles complicate large field-of-view fMRI experiments (e.g., experiments covering multiple visual areas instead of focusing on a single cortical region). Here, we use SE BOLD to acquire retinotopic mapping data in early visual areas, testing the feasibility of SE BOLD experiments spanning multiple cortical areas at 7T. We also use a recently developed method for normalizing signal intensity in T₁-weighted anatomical images to enable automated segmentation of the cortical gray matter for scans acquired at 7T with either surface or volume coils. We find that the CNR of the 7T GE data (average single-voxel, single-scan stimulus coherence: 0.41) is almost twice that of the 3T GE BOLD data (average coherence: 0.25), with the CNR of the SE BOLD data (average coherence: 0.23) comparable to that of the 3T GE data. Repeated measurements in individual subjects find that maps acquired with 1.8-mm resolution at 3T and 7T with GE BOLD and at 7T with SE BOLD show no systematic differences in either the area or the boundary locations for V1, V2 and V3, demonstrating the feasibility of high-resolution SE BOLD experiments with good sensitivity throughout multiple visual areas.     

Blood oxygen level-dependent and perfusion magnetic resonance imaging: detecting differences in oxygen bioavailability and blood flow in transplanted kidneys

Functional magnetic resonance imaging (fMRI) is a powerful tool for examining kidney function, including organ blood flow and oxygen bioavailability. We have used contrast enhanced perfusion and blood oxygen level-dependent (BOLD) MRI to assess kidney transplants with normal function, acute tubular necrosis (ATN) and acute rejection. BOLD and MR-perfusion imaging were performed on 17 subjects with recently transplanted kidneys. There was a significant difference between medullary R2? values in the group with acute rejection (R2?=16.2/s) compared to allografts with ATN (R2?=19.8/s; P=.047) and normal-functioning allografts (R2?=24.3/s;P=.0003). There was a significant difference between medullary perfusion measurements in the group with acute rejection (124.4±41.1 ml/100 g per minute) compared to those in patients with ATN (246.9±123.5 ml/100 g per minute; P=.02) and normal-functioning allografts (220.8±95.8 ml/100 g per minute; P=.02). This study highlights the utility of combining perfusion and BOLD MRI to assess renal function. We have demonstrated a decrease in medullary R2? (decrease deoxyhemoglobin) on BOLD MRI and a decrease in medullary blood flow by MR perfusion imaging in those allografts with acute rejection, which indicates an increase in medullary oxygen bioavailability in allografts with rejection, despite a decrease in blood flow.     

Oxygen-sensitive 19F NMR imaging of the vascular system in vivo

The fluorine nuclear magnetic resonance spin-lattice relaxation rate (1/T1) of the perfluorochemical blood substitute perfluorotripropylamine (FTPA) is very sensitive to oxygen tension. This presents the possibility of measuring blood oxygen tension by 19F MR imaging. We obtained oxygen-sensitive 19F NMR images of the circulatory system of rats infused with emulsified FTPA. Blood oxygenation was assessed under conditions of both air- and 100% O2-breathing. T1 relaxation times were derived from MR images using a partial saturation pulse sequence. The T1 times were compared with a phantom calibration curve to calculate average blood pO2 values in the lung, liver, and spleen. The results showed marked, organ-specific increases in blood oxygen tension when the rat breathed 100% O2 instead of air.     

What the little differences between men and women tells us about the BOLD response

We analyzed the functional MRI signal of 15 men and 15 women. All had been presented with a flashed and a reversing, radial checkerboard stimulus. We investigated both positive and negative blood oxygenation level-dependent (BOLD) responses. The extent of activation and the change in the neuronal activity were examined. The former, by counting the number of activated voxels, the latter by using deltaR2* as an indicator of the change in the local deoxyhemoglobin (HbR) concentration. We examined both the positive and the negative BOLD response. Positive BOLD response: The flashed checkerboard gave rise to a larger number of activated voxels than for the reversing checkerboard. The mean number of activated pixels did not differ between men and women. The peak deltaR2* was significantly larger to the flashed than the reversing checkerboard, but did not reveal a gender-related difference. We noted an attenuation of the BOLD signal amplitude with time. This attenuation was larger in women than in men. Negative BOLD response: The attenuation was also larger for the flashed than the reversing stimulus and more pronounced in the chromatic contrast compared to the luminance contrast stimulus. The extent of activation was larger for the flashed than the reversing checkerboard, but did not differ between the sexes. The deltaR2* for the chromatic contrast checkerboard was larger in men than in women. No other significant differences were found. We conclude that the difference in the extent of activation between men and women is the result of our ability to detect activated pixels using statistical methods and not the result of a difference in the processing between the sexes.     

Simultaneous BOLD/perfusion measurement using dual-echo FAIR and UNFAIR: sequence comparison at 1.5T and 3.0T.

Functional MRI (fMRI) studies designed for simultaneously measuring Blood Oxygenation Level Dependent (BOLD) and Cerebral Blood Flow (CBF) signal often employ the standard Flow Alternating Inversion Recovery (FAIR) technique. However, some sensitivity is lost in the BOLD data due to inherent T1 relaxation. We sought to minimize the preceding problem by employing a modified UN-inverted FAIR (UNFAIR) technique, which (in theory) should provide identical CBF signal as FAIR with minimal degradation of the BOLD signal. UNFAIR BOLD maps acquired from human subjects (n = 8) showed significantly higher mean z-score of approximately 17% (p < 0.001), and number of activated voxels at 1.5T. On the other hand, the corresponding FAIR perfusion maps were superior to the UNFAIR perfusion maps as reflected in a higher mean z-score of approximately 8% (p = 0.013), and number of activated voxels. The reduction in UNFAIR sensitivity for perfusion is attributed to increased motion sensitivity related to its higher background signal, and, T2 related losses from the use of an extra inversion pulse. Data acquired at 3.0T demonstrating similar trends are also presented.     

MAPPING HUMAN BRAIN FUNCTION WITH MRI AT 7 TESLA

In the past decade, the most significant development in MRI is the introduction of fMRI, which permits the mapping of human brain function with exquisite details non invasively. Functional mapping can be achieved by measuring changes in the blood oxygenation level (I.e. The BOLD contrast) or cerebral blood flow.