Blood Oxygen Level-dependent Technique Research Articles

Cerebrovascular reactivity measured with arterial spin labeling and blood oxygen level dependent techniques

PurposeTo compare cerebrovascular reactivity (CVR) quantified with pseudo-continuous arterial spin labeling (pCASL) and blood oxygen level dependent (BOLD) fMRI techniques. Materials and MethodsSixteen healthy volunteers (age: 37.8±14.3years; 6 women and 10 men; education attainment: 17±2.1years) were recruited and completed a 5% CO2 gas-mixture breathing paradigm at 3T field strength. ASL and BOLD images were acquired for CVR determination assuming that mild hypercapnia does not affect the cerebral metabolic rate of oxygen. Both CVR quantifications were derived as the ratio of the fractional cerebral blood flow (CBF) or BOLD signal change over the change in end-tidal CO2 pressure. ResultsThe absolute CBF, BOLD and CVR measures were consistent with literature values. CBF derived CVR was 5.11±0.87%/mmHg in gray matter (GM) and 4.64±0.37%/mmHg in parenchyma. BOLD CVR was 0.23±0.04%/mmHg and 0.22±0.04%/mmHg for GM and parenchyma respectively. The most significant correlations between BOLD and CBF-based CVRs were also in GM structures, with greater vascular response in occipital cortex than in frontal and parietal lobes (6.8%/mmHg versus 4.5%/mmHg, 50% greater). Parenchymal BOLD CVR correlated significantly with the fractional change in CBF in response to hypercapnia (r=0.61, P=0.01), suggesting the BOLD response to be significantly flow driven. GM CBF decreased with age in room air (−5.58mL/100g/min per decade for GM; r=−0.51, P=0.05), but there was no association of CBF with age during hypercapnia. A trend toward increased pCASL CVR with age was observed, scaling as 0.64%/mmHg per decade for GM. ConclusionConsistent with previously reported CVR values, our results suggest that BOLD and CBF CVR techniques are complementary to each other in evaluating neuronal and vascular underpinning of hemodynamic processes.

Myocardial oxygenation is impaired in advanced chronic kidney disease and renal transplant patients

Background Coronary artery disease (CAD) and left ventricular hypertrophy are prevalent in the chronic kidney disease (CKD) and renal transplant population. Advances in cardiovascular magnetic resonance (CMR) with the blood oxygen level-dependent (BOLD) technique provides unprecedented capability to assess myocardial oxygenation as a measure of ischaemia. We hypothesised that myocardial oxygenation would be reduced in advanced CKD and renal transplant patients and may provide a novel strategy for assessing myocardial ischaemia. Methods We prospectively studied 20 advanced CKD subjects (8 dialysis group with median eGFR 9.5 (range 5-37) ml/ min and 12 CKD group with median eGFR 14 (range 818) ml/min), 8 renal transplant (RT) recipients with median eGFR 74.5 (range 57-114) ml/min and 7 hypertensive (HT) controls with median eGFR 107 (range 57144) ml/min. All patients were asymptomatic for CAD and none had prior history of CAD. All groups had cine and BOLD CMR at 3T, and RT and HT groups also had late gadolinium CMR to assess infarction/replacement fibrosis. CKD group additionally underwent 2D echocardiography strain to assess fibrosis. Myocardial oxygenation was measured at rest and under stress with adenosine (140 µg/kg/min) using BOLD Signal Intensity (SI). Analyses were performed using linear mixed models. Results

Calibrating the BOLD response without administering gases: Comparison of hypercapnia calibration with calibration using an asymmetric spin echo

The calibrated BOLD (blood oxygen level dependent) technique was developed to quantify the BOLD signal in terms of changes in oxygen metabolism. In order to achieve this a calibration experiment must be performed, which typically requires a hypercapnic gas mixture to be administered to the participant. However, an emerging technique seeks to perform this calibration without administering gases using a refocussing based calibration. Whilst hypercapnia calibration seeks to emulate the physical removal of deoxyhaemoglobin from the blood, the aim of refocussing based calibration is to refocus the dephasing effect of deoxyhaemoglobin on the MR signal using a spin echo. However, it is not possible to refocus all of the effects that contribute to the BOLD signal and a scale factor is required to estimate the BOLD scaling parameter M. In this study the feasibility of a refocussing based calibration was investigated. The scale factor relating the refocussing calibration to M was predicted by simulations to be approximately linear and empirically measured to be 0.88±0.36 for the visual cortex and 0.93±0.32 for a grey matter region of interest (mean±standard deviation). Refocussing based calibration is a promising approach for greatly simplifying the calibrated BOLD methodology by eliminating the need for the subject to breathe special gas mixtures, and potentially provides the basis for a wider implementation of quantitative functional MRI.

Arterial cerebral blood volume-weighted functional MRI using pseudocontinuous arterial spin tagging (AVAST).

Neurovascular regulation, including responses to neural activation that give rise to the blood oxygenation level-dependent (BOLD) effect, occurs mainly at the arterial and arteriolar level. The purpose of this study is to develop a framework for fast imaging of arterial cerebral blood volume (aCBV) signal suitable for functional imaging studies. A variant of the pseudocontinuous arterial spin tagging technique was developed in order to achieve a contrast that depends on aCBV with little contamination from perfusion signal by taking advantage of the kinetics of the tag through the vasculature. This technique tailors the tagging duration and repetition time for each subject. The proposed technique, called AVAST, is compared empirically with BOLD imaging and standard (perfusion-weighted) arterial spin labeling (ASL) technique, in a motor-visual activation paradigm. The average Z-scores in the activated area obtained over all the subjects were 4.25, 5.52, and 7.87 for standard ASL, AVAST, and BOLD techniques, respectively. The aCBV contrast obtained from AVAST provided 80% higher average signal-to-noise ratio and 95% higher average contrast-to-noise ratio compared with that of the standard ASL measurements. AVAST exhibits improved activation detection sensitivity and temporal resolution over the standard ASL technique, in functional MRI experiments, while preserving its quantitative nature and statistical advantages. AVAST particularly could be useful in clinical studies of pathological conditions, longitudinal studies of cognitive function, and studies requiring sustained periods of the condition.

Clinical utility of BOLD fMRI in preoperative work-up of epilepsy.

Surgical techniques have emerged as a viable therapeutic option in patients with drug refractory epilepsy. Pre-surgical evaluation of epilepsy requires a comprehensive, multiparametric, and multimodal approach for precise localization of the epileptogenic focus. Various non-invasive techniques are available at the disposal of the treating physician to detect the epileptogenic focus, which include electroencephalography (EEG), video-EEG, magnetic resonance imaging (MRI), functional MRI including blood oxygen level dependent (BOLD) techniques, single photon emission tomography (SPECT), and 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET). Currently, non-invasive high-resolution MR imaging techniques play pivotal roles in the preoperative detection of the seizure focus, and represent the foundation for successful epilepsy surgery. BOLD functional magnetic resonance imaging (fMRI) maps allow for precise localization of the eloquent cortex in relation to the seizure focus. This review article focuses on the clinical utility of BOLD (fMRI) in the pre-surgical work-up of epilepsy patients.

Myocardial oxygenation is reduced in end-stage renal failure: a novel blood oxygen level dependant (BOLD)-cardiac MRI study

Background Cardiovascular disease is the leading cause of mortality and morbidity in end-stage renal failure (ESRF) population, mostly from coronary artery disease (CAD). Majority of CAD in ESRF patients is asymptomatic and current cardiac stress imaging modalities are sub-optimal as risk predictors. Advances in cardiovascular magnetic resonance (CMR) with the novel blood oxygen level-dependent (BOLD) technique provides unprecedented capability to assess regional myocardial deoxygenation. We hypothesized that myocardial oxygenation would be reduced in ESRF patients and may form a novel strategy to assess myocardial ischemia. Methods Sixteen chronic renal failure (CRF) patients (7 on dialysis, 9 pre-dialysis) with no known history of CAD underwent CMR scanning at 3.0 T. Given known reductions in BOLD signals in hypertrophied myocardium, we also assessed a control group of HT patients with no history of CAD (n = 6) Myocardial function, rest and stress BOLD was performed. To measure oxygenation, using a T2-prepared BOLD sequence, myocardial Signal Intensity (SI) was measured at adenosine stress (140 μg/ kg/min) and at rest (corrected to RR interval). Comparison of myocardial SI analyses were performed using multivariate linear regression. Results

Abnormal GABAergic Function and Negative Affect in Schizophrenia

Deficits in the γ-aminobutyric acid (GABA) system have been reported in postmortem studies of schizophrenia, and therapeutic interventions in schizophrenia often involve potentiation of GABA receptors (GABAR) to augment antipsychotic therapy and treat negative affect such as anxiety. To map GABAergic mechanisms associated with processing affect, we used a benzodiazepine challenge while subjects viewed salient visual stimuli. Fourteen stable, medicated schizophrenia/schizoaffective patients and 13 healthy comparison subjects underwent functional magnetic resonance imaging using the blood oxygenation level-dependent (BOLD) technique while they viewed salient emotional images. Subjects received intravenous lorazepam (LRZ; 0.01 mg/kg) or saline in a single-blinded, cross-over design (two sessions separated by 1-3 weeks). A predicted group by drug interaction was noted in the dorsal medial prefrontal cortex (dmPFC) as well as right superior frontal gyrus and left and right occipital regions, such that psychosis patients showed an increased BOLD signal to LRZ challenge, rather than the decreased signal exhibited by the comparison group. A main effect of reduced BOLD signal in bilateral occipital areas was noted across groups. Consistent with the role of the dmPFC in processing emotion, state negative affect positively correlated with the response to the LRZ challenge in the dmPFC for the patients and comparison subjects. The altered response to LRZ challenge is consistent with altered inhibition predicted by postmortem findings of altered GABAR in schizophrenia. These results also suggest that negative affect in schizophrenia/schizoaffective disorder is associated-directly or indirectly-with GABAergic function on a continuum with normal behavior.

Detecting resting-state brain activity by spontaneous cerebral blood volume fluctuations using whole brain vascular space occupancy imaging

Resting-state brain activity has been investigated extensively using BOLD contrast. However, BOLD signal represents the combined effects of multiple physiological processes and its spatial localization is less accurate than that of cerebral blood flow and volume (CBF and CBF, respectively). In this study, we demonstrate that resting-state brain activity can be reliably detected by spontaneous fluctuations of CBV-weighted signal using whole-brain gradient and spin echo (GRASE) based vascular space occupancy (VASO) imaging. Specifically, using independent component analysis, intrinsic brain networks, including default mode, salience, executive control, visual, auditory, and sensorimotor networks were revealed robustly by the VASO technique. We further demonstrate that task-evoked VASO signal aligned well with expected gray matter areas, while blood-oxygenation level dependent (BOLD) signal extended outside of these areas probably due to their different spatial specificity. The improved spatial localization of VASO is consistent with previous studies using animal models. Moreover, we showed that the 3D-GRASE VASO images had reduced susceptibility-induced signal voiding, compared to the BOLD technique. This is attributed to the fact that VASO does not require T2* weighting, thus the acquisition can use a shorter TE and can employ spin-echo scheme. Consequently VASO-based functional connectivity signals were well preserved in brain regions that tend to suffer from signal loss and geometric distortion in BOLD, such as orbital prefrontal cortex. Our study suggests that 3D-GRASE VASO imaging, with its improved spatial specificity and less sensitivity to susceptibility artifacts, may have advantages in resting-state fMRI studies.

The role of BOLD-fMRI in elucidating migraine pathophysiology

Migraine is a neurologic disorder characterized by disabling attacks of throbbing headache with specific features and associated symptoms. Despite the recent discoveries in basic neurosciences, migraine pathophysiology is not completely understood. Nevertheless, in the last decades, advances in functional magnetic resonance imaging (fMRI) have significantly provided new insights into migraine mechanisms. Blood oxygen level dependent (BOLD) fMRI technique is the most commonly used method to explore brain function and connectivity due to high temporal and spatial resolution. The purpose of this review is to present a synthesis of recent BOLD-fMRI studies which have allowed us to elucidate the complex process involved in migraine pathophysiology.

Multi-shot turbo spin-echo for 3D vascular space occupancy imaging

Vascular space occupancy (VASO) is a magnetic resonance imaging technique sensitive to cerebral blood volume, and is a potential alternative to the blood oxygenation level dependent (BOLD) sensitive technique as a basis for functional mapping of the neurovascular response to a task. Many implementations of VASO have made use of echo-planar imaging strategies that allow rapid acquisition, but risk introducing potentially confounding BOLD effects. Recently, multi-slice and 3D VASO techniques have been implemented to increase the imaging volume beyond the single slice of early reports. These techniques usually rely, however, on advanced scanner software or hardware not yet available in many centers. In the present study, we have implemented a short-echo time, multi-shot 3D Turbo Spin-Echo (TSE) VASO sequence that provided 8-slice coverage on a routine clinical scanner. The proposed VASO sequence was tested in assessing the response of the human motor cortex during a block design finger tapping task in 10 healthy subjects. Significant VASO responses, inversely correlated with the task, were found at both individual and group level. The location and extent of VASO responses were in close correspondence to those observed using a conventional BOLD acquisition in the same subjects. Although the spatial coverage and temporal resolution achieved were limited, robust and consistent VASO responses were observed. The use of a susceptibility insensitive volumetric TSE VASO sequence may have advantages in locations where conventional BOLD and echo-planar based VASO imaging is compromised.

Changes in human fetal oxygenation during maternal hyperoxia as estimated by BOLD MRI

Changes in blood oxygen level dependent (BOLD) magnetic resonance imaging (MRI) signal are closely related to changes in fetal oxygenation. In this study, we aimed to investigate the changes in human fetal oxygenation during maternal hyperoxia by using the non-invasive BOLD MRI technique. Eight healthy pregnant women in gestational week 28 to 34 were included. With the use of a facial oxygen mask, we induced maternal hyperoxia and measured changes in the BOLD MRI signal of selected fetal organs. In a number of fetal organs, the BOLD MRI signal increased significantly (P < 0.01) during maternal hyperoxia (mean change in % ± SEM): liver (14.3 ± 3.7%), spleen (15.2 ± 3.5%) and kidney (6.2 ± 1.8%) as well as the placenta (6.5 ± 1.6%). In the fetal brain, however, the BOLD MRI signal remained constant (0.3 ± 0.2%). During maternal hyperoxia, we demonstrated an increased oxygenation in a number of human fetal organs by using the non-invasive BOLD technique. The oxygenation of the fetal brain remained constant, thus a 'reversed' brain sparing mechanism could be considered in healthy fetuses subjected to hyperoxia.

Short-Term Caloric Restriction Normalizes Hypothalamic Neuronal Responsiveness to Glucose Ingestion in Patients With Type 2 Diabetes

The hypothalamus is critically involved in the regulation of feeding. Previous studies have shown that glucose ingestion inhibits hypothalamic neuronal activity. However, this was not observed in patients with type 2 diabetes. Restoring energy balance by reducing caloric intake and losing weight are important therapeutic strategies in patients with type 2 diabetes. We hypothesized that caloric restriction would have beneficial effects on the hypothalamic neuronal response to glucose ingestion. Functional magnetic resonance imaging was performed in 10 male type 2 diabetic patients before and after a 4-day very-low-calorie diet (VLCD) at a 3.0 Tesla scanner using a blood oxygen level–dependent technique for measuring neuronal activity in the hypothalamus in response to an oral glucose load. Hypothalamic signals were normalized to baseline value, and differences between the pre- and postdiet condition were tested using paired t tests. Pre-VLCD scans showed no response of the hypothalamus to glucose intake (i.e., no signal decrease after glucose intake was observed). Post-VLCD scans showed a prolonged signal decrease after glucose ingestion. The results of the current study demonstrate that short-term caloric restriction readily normalizes hypothalamic responsiveness to glucose ingestion in patients with type 2 diabetes.

Blood oxygenation level‐dependent (BOLD) contrast magnetic resonance imaging (MRI) for prediction of breast cancer chemotherapy response: A pilot study

To determine whether a simple noninvasive method of assessing tumor oxygenation is feasible in the clinical setting and can provide useful, potentially predictive information. Tumor microcirculation and oxygenation play critical roles in tumor growth and responsiveness to cytotoxic treatment and may provide prognostic indicators for cancer therapy. Deoxyhemoglobin is paramagnetic and can serve as an endogenous contrast agent causing signal loss in echo planar magnetic resonance imaging (MRI) (blood oxygenation level-dependent [BOLD]-MRI). We used BOLD-MRI to provide early evaluation of response to neoadjuvant chemotherapy in patients with locally advanced breast cancer. MRI was performed on 11 patients with biopsy-proven malignancy. MRI exams were scheduled before, during, and after chemotherapy. The BOLD study applied a 6-minute oxygen breathing challenge. Seven patients successfully completed the exams. Before chemotherapy, BOLD contrast enhancement was observed in all tumors, but the patients, who ultimately had complete pathological response, exhibited a significantly higher BOLD response to oxygen breathing. We have successfully implemented an oxygen-breathing challenge BOLD contrast technique as part of the standard breast MRI exam in patients with locally advanced breast cancer. The preliminary observation that a large BOLD response correlated with better treatment response suggests a predictive capability for BOLD MRI.

A review of calibrated blood oxygenation level‐dependent (BOLD) methods for the measurement of task‐induced changes in brain oxygen metabolism

The dynamics of the blood oxygenation level-dependent (BOLD) response are dependent on changes in cerebral blood flow, cerebral blood volume and the cerebral metabolic rate of oxygen consumption. Furthermore, the amplitude of the response is dependent on the baseline physiological state, defined by the haematocrit, oxygen extraction fraction and cerebral blood volume. As a result of this complex dependence, the accurate interpretation of BOLD data and robust intersubject comparisons when the baseline physiology is varied are difficult. The calibrated BOLD technique was developed to address these issues. However, the methodology is complex and its full promise has not yet been realised. In this review, the theoretical underpinnings of calibrated BOLD, and issues regarding this theory that are still to be resolved, are discussed. Important aspects of practical implementation are reviewed and reported applications of this methodology are presented.

Optimization strategies for evaluation of brain hemodynamic parameters with qBOLD technique

Quantitative blood oxygenation level dependent technique provides an MRI-based method to measure tissue hemodynamic parameters such as oxygen extraction fraction and deoxyhemoglobin-containing (veins and prevenous part of capillaries) cerebral blood volume fraction. It is based on a theory of MR signal dephasing in the presence of blood vessel network and experimental method-gradient echo sampling of spin echo previously proposed and validated on phantoms and animals. In vivo human studies also demonstrated feasibility of this approach but also recognized that obtaining reliable results requires high signal-to-noise ratio in the data. In this paper, we analyze in detail the uncertainties of the quantitative blood oxygenation level dependent parameter estimates in the framework of the Bayesian probability theory, namely, we examine how the estimated parameters oxygen extraction fraction and deoxygenated cerebral blood volume fraction depend on their "true values," signal-to-noise ratio, and data sampling strategies. On the basis of this analysis, we develop strategies for optimization of the quantitative blood oxygenation level dependent technique for deoxygenated cerebral blood volume and oxygen extraction fraction evaluation. In particular, it is demonstrated that the use of gradient echo sampling of spin echo sequence allows substantial decrease of measurement errors as the data are acquired on both sides of spin echo. We test our theory on phantom mimicking the structure of blood vessel network. A 3D gradient echo sampling of spin echo pulse sequence is used for the acquisition of the MRI signal that was subsequently analyzed by Bayesian Application Software. The experimental results demonstrated a good agreement with theoretical predictions.

Oxygen Imaging by MRI

Mapping the ischemic penumbra (ie, the neurophysiologically silent but still viable ischemic tissue) is increasingly part of routine assessment in suspected acute stroke, although whether this approach is cost-effective is still unclear.1,2 The penumbra is characterized by both low cerebral blood flow (CBF; <20 mL · 100 g−1 · min−1) and elevated oxygen extraction fraction (OEF).3 The latter is considered a critical marker of tissue viability and is therefore a key imaging target. The penumbra was originally documented in humans using positron emission tomography (PET),2,3 a validated method to map CBF, OEF and cerebral metabolic rate of oxygen (CMRO2),4 but clinical access to PET is scarce. Consequently, MR-based diffusion and perfusion imaging (PWI) and CT-based perfusion imaging are widely used as substitutes.1 However, both methods have limitations for penumbra imaging2 and do not directly assess oxygen metabolism. A method combining the advantages of MR and the ability to map OEF would therefore be highly desirable. Blood oxygen level-dependent (BOLD) imaging has recently emerged as a possible candidate for this purpose. However, several BOLD techniques with different levels of validation, accuracy, and clinical applicability are in concurrent development, making the situation somewhat confusing. This review aims to clarify whether BOLD imaging might be of use to map oxygen in the clinical setting. We systematically review and critically discuss all studies published to date in English language, both experimental and clinical, that have applied BOLD in acute stroke. Because our focus is tissue oxygen metabolism, we do not address the T2*-weighted method to visualize leptomeningeal vessels,5 the mapping of ΔCMRO2 during physiological challenges,6 or the emerging 17O imaging method.7 ### Principles of BOLD MRI Oxyhemoglobin is diamagnetic, whereas deoxyhemoglobin (DHb) is paramagnetic. Transverse relaxation is sensitive to paramagnetic …

Myocardial Oxygenation in Coronary Artery Disease: Insights From Blood Oxygen Level–Dependent Magnetic Resonance Imaging at 3 Tesla

The purpose of this study was to assess the diagnostic accuracy of blood oxygen-level dependent (BOLD) MRI in suspected coronary artery disease (CAD). By exploiting the paramagnetic properties of deoxyhemoglobin, BOLD magnetic resonance imaging can detect myocardial ischemia. We applied BOLD imaging and first-pass perfusion techniques to: 1) examine the pathophysiological relationship between coronary stenosis, perfusion, ventricular scar, and myocardial oxygenation; and 2) evaluate the diagnostic performance of BOLD imaging in the clinical setting. BOLD and first-pass perfusion images were acquired at rest and stress (4 to 5 min intravenous adenosine, 140 μg/kg/min) and assessed quantitatively (using a BOLD signal intensity index [stress/resting signal intensity], and absolute quantification of perfusion by model-independent deconvolution). A BOLD signal intensity index threshold to identify ischemic myocardium was first determined in a derivation arm (25 CAD patients and 20 healthy volunteers). To determine diagnostic performance, this was then applied in a separate group comprising 60 patients with suspected CAD referred for diagnostic angiography. Prospective evaluation of BOLD imaging yielded an accuracy of 84%, a sensitivity of 92%, and a specificity of 72% for detecting myocardial ischemia and 86%, 92%, and 72%, respectively, for identifying significant coronary stenosis. Segment-based analysis revealed evidence of dissociation between oxygenation and perfusion (r = -0.26), with a weaker correlation of quantitative coronary angiography with myocardial oxygenation (r = -0.20) than with perfusion (r = -0.40; p = 0.005 for difference). Hypertension increased the odds of an abnormal BOLD response, but diabetes mellitus, hypercholesterolemia, and the presence of ventricular scar were not associated with significant deoxygenation. BOLD imaging provides valuable insights into the pathophysiology of CAD; myocardial hypoperfusion is not necessarily commensurate with deoxygenation. In the clinical setting, BOLD imaging achieves favorable accuracy for identifying the anatomic and functional significance of CAD.

Brain Reorganization in Patients with Brachial Plexus Injury: A Longitudinal Functional MRI Study

The aim of this study is to assess plastic changes of the sensorimotor cortex (SMC) in patients with traumatic brachial plexus injury (BPI) using functional magnetic resonance imaging (fMRI). Twenty patients with traumatic BPI underwent fMRI using blood oxygen level-dependent technique with echo-planar imaging before the operation. Sixteen patients underwent their second fMRI at approximately one year after injury. The subjects performed two tasks: a flexion-extension task of the affected elbow and a task of the unaffected elbow. After activation, maps were generated, the number of significantly activated voxels in SMC contralateral to the elbow movement in the affected elbow task study (N af) and that in the unaffected task study (N unaf) were counted. An asymmetry index (AI) was calculated, where AI = (N af − N unaf)/(N af + N unaf). Ten healthy volunteers were also included in this fMRI study. The AI of the first fMRI of the patients with BPI was significantly lower than that of the healthy subjects (P = 0.035). The AI of the second fMRI significantly decreased compared with that of the first fMRI (P = 0.045). Brain reorganization associates with peripheral nervous changes after BPI and after operation for functional reconstruction.

Left–right difference in fetal liver oxygenation during hypoxia estimated by BOLD MRI in a fetal sheep model

The purpose of this study was to measure differences in oxygenation between the left and right sides of the fetal liver during varying oxygenation levels. Eight ewes carrying singleton fetuses at gestational age 125 days (term, 145 days) were included in the study. Under anesthesia the ewes were ventilated with gas containing different levels of oxygen, thereby subjecting the fetuses to hyperoxia (mean ± SD maternal arterial partial pressure of oxygen (pO2), 23.2 ± 8.2 kPa) and hypoxia (mean maternal arterial pO2, 7.1 ± 0.5 kPa). Changes in oxygenation within the fetal liver were assessed by blood oxygen level-dependent (BOLD) magnetic resonance imaging (MRI). During hyperoxia there was no difference between the BOLD signal in the left and right sides of the fetal liver; mean change in BOLD (ΔBOLD)(hyperox), -0.9 ± 3.7%. During hypoxia, however, the decrease in the BOLD signal was more pronounced in the right side as compared with the left side, thereby creating a significant increase in the left-right difference in the BOLD signal; mean ΔBOLD(hypox), 5.2 ± 2.2% (P = 0.002, paired t-test). The left-right difference was directly proportional to the degree of hypoxia (R2 = 0.86, P = 0.007). To our knowledge, this is the first study demonstrating differences in oxygenation between the left and right sides of the fetal liver during hypoxia, a difference that can be explained by increased ductus venosus shunting. Thus, the BOLD MRI technique is a promising non-invasive tool that might be useful for the future monitoring of the human fetus.

Spatio-temporal activity in real time (STAR): Optimization of regional fMRI feedback

The use of real-time feedback has expanded fMRI from a brain probe to include potential brain interventions with significant therapeutic promise. However, whereas time-averaged blood oxygenation level-dependent (BOLD) signal measurement is usually sufficient for probing a brain state, the real-time (frame-to-frame) BOLD signal is noisy, compromising feedback accuracy. We have developed a new real-time processing technique (STAR) that combines noise-reduction properties of multi-voxel (e.g., whole-brain) techniques with the regional specificity critical for therapeutics. Nineteen subjects were given real-time feedback in a cognitive control task (imagining repetitive motor activity vs. spatial navigation), and were all able to control a visual feedback cursor based on whole-brain neural activity. The STAR technique was evaluated, retrospectively, for five a priori regions of interest in these data, and was shown to provide significantly better (frame-by-frame) classification accuracy than a regional BOLD technique. In addition to regional feedback signals, the output of the STAR technique includes spatio-temporal activity maps (movies) providing insight into brain dynamics. The STAR approach offers an appealing optimization for real-time fMRI applications requiring an anatomically-localized feedback signal.