Oxygen Level-dependent Magnetic Resonance Research Articles

Application of BOLD Magnetic Resonance Imaging for Evaluating Regional Volumetric Foot Tissue Oxygenation: A Feasibility Study in Healthy Volunteers

To evaluate the feasibility and repeatability of applying blood oxygen level-dependent (BOLD) magnetic resonance imaging (MRI) in the feet to quantify regional dynamic changes in tissue oxygenation during proximal cuff occlusion and reactive hyperemia. Ten healthy male subjects underwent BOLD and T1-weighted imaging of the feet on two separate occasions, using a 3-T scanner. Dynamic changes in BOLD signal intensity were assessed before and during proximal cuff occlusion of the thigh and during reactive hyperemia, and BOLD time course data were evaluated for the time-to-half ischemic minimum, minimum ischemic value, peak hyperemic value, time-to-peak hyperemia, time-to-half peak hyperemia, and end value. T1-weighted images were used for segmentation of volumes of interest (VOI) in anatomical regions of the foot (heel, toes, dorsal foot, medial and lateral plantar foot). Repeatability of vascular responses was assessed for each foot VOI using semiautomated image registration and quantification of serial BOLD images. The heel VOI demonstrated a significantly higher peak hyperemic response, expressed as percent change from baseline BOLD signal intensity, compared with all other VOIs of the foot (heel, 7.4±1.2%; toes, 5.6±0.8%; dorsal foot, 5.7±1.6%; medial plantar, 5.6±1.7%; lateral plantar, 5.6±1.5% [p<.05]). Additionally, the lateral plantar VOI had a significantly lower terminal signal intensity value (i.e., end value) when compared with all foot VOIs (p<.05). BOLD MRI was repeatable between visits in all foot VOIs, with no significant differences between study visits for any of the evaluated functional indices. BOLD MRI offers a repeatable technique for volumetric assessment of regional foot tissue oxygenation. Future application of BOLD imaging in the feet of patients with peripheral vascular disease may permit serial evaluation of regional tissue oxygenation and allow for improved assessment of therapeutic interventions targeting specific sites of the foot.

Differences in GFR and Tissue Oxygenation, and Interactions between Stenotic and Contralateral Kidneys in Unilateral Atherosclerotic Renovascular Disease.

Atherosclerotic renal artery stenosis (ARAS) can reduce renal blood flow, tissue oxygenation, and GFR. In this study, we sought to examine associations between renal hemodynamics and tissue oxygenation with single-kidney function, pressor hormones, and inflammatory biomarkers in patients with unilateral ARAS undergoing medical therapy alone or stent revascularization. Nonrandomized inpatient studies were performed in patients with unilateral ARAS (>60% occlusion) before and 3 months after revascularization (n=10) or medical therapy (n=20) or patients with essential hypertension (n=32) under identical conditions. The primary study outcome was change in single-kidney GFR. Individual kidney hemodynamics and volume were measured using multidetector computed tomography. Tissue oxygenation (using R(2)* as a measure of deoxyhemoglobin) was determined by blood oxygen level-dependent magnetic resonance imaging at 3 T. Renal vein neutrophil gelatinase-associated lipocalin (NGAL), monocyte chemoattractant protein-1 (MCP-1), and plasma renin activity were measured. Total GFR did not change over 3 months in either group, but the stenotic kidney (STK) GFR rose over time in the stent compared with the medical group (+2.2[-1.8 to 10.5] versus -5.3[-7.3 to -0.3] ml/min; P=0.03). Contralateral kidney (CLK) GFR declined in the stent group (43.6±19.7 to 36.6±19.5 ml/min; P=0.03). Fractional tissue hypoxia fell in the STK (fraction R(2)* >30/s: 22.1%±20% versus 14.9%±18.3%; P<0.01) after stenting. Renal vein biomarkers correlated with the degree of hypoxia in the STK: NGAL(r=0.3; P=0.01) and MCP-1(r=0.3; P=0.02; more so after stenting). Renal vein NGAL was inversely related to renal blood flow in the STK (r=-0.65; P<0.001). Biomarkers were highly correlated between STK and CLK, NGAL (r=0.94; P<0.001), and MCP-1 (r=0.96; P<0.001). These results showed changes over time in single-kidney GFR that were not evident in parameters of total GFR. Furthermore, they delineate the relationship of measurable tissue hypoxia within the STK and markers of inflammation in human ARAS. Renal vein NGAL and MCP-1 indicated persistent interactions between the ischemic kidney and both CLK and systemic levels of inflammatory cytokines.

Reduced placental oxygenation during subclinical uterine contractions as assessed by BOLD MRI

ObjectivesDuring placental Blood Oxygen Level Dependent (BOLD) Magnetic Resonance Imaging (MRI), we have observed spontaneous reductions in placental oxygenation lasting 2–4 min. We hypothesize, that these reductions in placental oxygenation are caused by subclinical uterine contractions. MethodsWe evaluated placental oxygenation during a five-minute placental BOLD MRI in 56 normal pregnancies (gestational week 23–40) and observed a spontaneous reduction in eight cases. The 56 BOLD MRIs were systematically analyzed for signs of uterine contractions, i.e. visual changes in uterus shape and reductions in the number of pixels within Regions of interest (ROI) covering the outline of the entire uterus. ResultsThe eight reductions in the BOLD signal lasted for 217 ± 51 (mean ± SD) seconds with an average signal loss of 17 ± 5%. They were all associated with a contraction, which started 43 ± 21 s prior to the start of the reduction and ended 71 ± 30 s prior to the end of the reduction. In the remaining 48 MRIs, we observed no contraction. ConclusionWe suggest that the observed spontaneous reductions in placental oxygenation are caused by uterine contractions. According to our data, subclinical uterine contractions occur regularly and have a markedly impact on placental oxygenation. Therefore, uterine contractions need to be considered in the interpretation of placental MRI as they may interfere with the MRI results.

Comparison of [(15)O] H2O Positron Emission Tomography and Functional Magnetic Resonance Imaging in Activation Studies.

[15O] H2O positron emission tomography (PET) has long been out of use in activation studies on the brain. Indeed, it is true that blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) has better spatial resolution and temporal resolution than PET, as well as no radiation exposure. However, PET and fMRI differ in their scope. Compared to fMRI, [15O] H2O PET offers advantages such as being quantifiable, less deteriorated by movement, and allowing for longitudinal studies. This article aimed to reassess the merits of PET in this context.

Monitoring of the tumor response to nano-graphene oxide-mediated photothermal/photodynamic therapy by diffusion-weighted and BOLD MRI.

Photothermal therapy (PTT) and photodynamic therapy (PDT) are promising cancer treatment modalities. Because each modality has its own set of advantages and limitations, there has been interest in developing methods that can co-deliver the two regimens for enhanced tumor treatment. Among the efforts, nano-graphene oxide-mediated phototherapies have recently attracted much attention. Nano-graphene oxide has a broad absorbance spectrum and can be loaded with photosensitizers, such as chlorin e6, with high efficiency. Chlorin e6-loaded and PEGylated nano-graphene (GO-PEG-Ce6) can be excited at 660 nm, 808 nm, or both, to induce PDT, PTT, or PDT/PTT combination. Despite the potential of the treatments, there is a lack of a diagnostic tool which can monitor their therapeutic response in a non-invasive and prognostic manner; such an ability is urgently needed for the transformation and translation of the technologies. In this study, we performed diffusion-weighted and blood oxygenation level dependent (BOLD) magnetic resonance imaging (MRI) after GO-PEG-Ce6-mediated PTT, PDT, or PTT/PDT. We found that after efficient PTT, there is a significant increase of the tumor apparent diffusion coefficient (ADC) value in diffusion-weighted imaging (DWI) maps; meanwhile, an efficient PDT led to an increase of in BOLD images. In both the cases, the amplitude of the increase was correlated with the treatment outcomes. More interestingly, a synergistic treatment efficacy was observed when the PTT/PDT combination was applied, and the combination was associated with a greater ADC and increase than when either modality was used alone. In particular, the PTT/PDT condition that induced the most dramatic short-term increase of the ADC value (>70%) caused the most effective tumor control in the long-run, with 60% of the treated animals being tumor-free after 60 days. These results suggest the great promise of the combination of DWI and BOLD MRI as a tool for accurate monitoring and prognosis of phototherapies, which is of great value to the future developments of the methodologies.

Beta-Blocker Use Is Associated with Higher Renal Tissue Oxygenation in Hypertensive Patients Suspected of Renal Artery Stenosis

Background: Chronic renal hypoxia influences the progression of chronic kidney disease (CKD). Blood oxygen level-dependent (BOLD) magnetic resonance (MR) is a noninvasive tool for the assessment of renal oxygenation. The impact of beta-blockers on renal hemodynamics and oxygenation is not completely understood. We sought to determine the association between beta-blocker use, renal cortical and medullary oxygenation, and renal blood flow in patients suspected of renal artery stenosis. Methods: We measured renal cortical and medullary oxygenation using BOLD MR and renal artery blood flow using MR phase contrast techniques in 38 participants suspected of renal artery stenosis. Results: Chronic beta-blocker therapy was associated with improved renal cortical (p < 0.001) and medullary (p = 0.03) oxygenation, while the use of calcium channel blockers or diuretics showed no association with either cortical or medullary oxygenation. Receipt of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers was associated with reduced medullary oxygenation (p = 0.01). In a multivariable model, chronic receipt of beta-blockers was the only significant predictor of renal tissue oxygenation (β = 8.4, p = 0.008). Beta-blocker therapy was not associated with significant changes in renal artery blood flow, suggesting that improved renal oxygenation may be related to reduced renal oxygen consumption. Conclusions: In addition to known benefits to reduce cardiovascular mortality in patients with renal disease, beta-blockers may reduce or prevent the progression of renal dysfunction in patients with hypertension, diabetes, and renovascular disease, partly by reducing renal oxygen consumption. These observations may have important implications for the treatment of patients with CKD.

259: The use of blood oxygen-level dependent magnetic resonance imaging (BOLD-MRI) in growth restricted fetuses

259: The use of blood oxygen-level dependent magnetic resonance imaging (BOLD-MRI) in growth restricted fetuses

Assessment of Renal Hemodynamics and Oxygenation by Simultaneous Magnetic Resonance Imaging (MRI) and Quantitative Invasive Physiological Measurements.

In vivo assessment of renal perfusion and oxygenation under (patho)physiological conditions by means of noninvasive diagnostic imaging is conceptually appealing. Blood oxygen level-dependent (BOLD) magnetic resonance imaging (MRI) and quantitative parametric mapping of the magnetic resonance (MR) relaxation times T 2* and T 2 are thought to provide surrogates of renal tissue oxygenation. The validity and efficacy of this technique for quantitative characterization of local tissue oxygenation and its changes under different functional conditions have not been systematically examined yet and remain to be established. For this purpose, the development of an integrative multimodality approaches is essential. Here we describe an integrated hybrid approach (MR-PHYSIOL) that combines established quantitative physiological measurements with T 2* (T 2) mapping and MR-based kidney size measurements. Standardized reversible (patho)physiologically relevant interventions, such as brief periods of aortic occlusion, hypoxia, and hyperoxia, are used for detailing the relation between the MR-PHYSIOL parameters, in particular between renal T 2* and tissue oxygenation.

Role of emotional processing in depressive responses to sex-hormone manipulation: a pharmacological fMRI study.

Sex-hormone fluctuations may increase risk for developing depressive symptoms and alter emotional processing as supported by observations in menopausal and pre- to postpartum transition. In this double-blinded, placebo-controlled study, we used blood−oxygen level dependent functional magnetic resonance imaging (fMRI) to investigate if sex-steroid hormone manipulation with a gonadotropin-releasing hormone agonist (GnRHa) influences emotional processing. Fifty-six healthy women were investigated twice: at baseline (follicular phase of menstrual cycle) and 16±3 days post intervention. At both sessions, fMRI-scans during exposure to faces expressing fear, anger, happiness or no emotion, depressive symptom scores and estradiol levels were acquired. The fMRI analyses focused on regions of interest for emotional processing. As expected, GnRHa initially increased and subsequently reduced estradiol to menopausal levels, which was accompanied by an increase in subclinical depressive symptoms relative to placebo. Women who displayed larger GnRHa-induced increase in depressive symptoms had a larger increase in both negative and positive emotion-elicited activity in the anterior insula. When considering the post-GnRHa scan only, depressive responses were associated with emotion-elicited activity in the anterior insula and amygdala. The effect on regional activity in anterior insula was not associated with the estradiol net decline, only by the GnRHa-induced changes in mood. Our data implicate enhanced insula recruitment during emotional processing in the emergence of depressive symptoms following sex-hormone fluctuations. This may correspond to the emotional hypersensitivity frequently experienced by women postpartum.

Renal Blood Oxygenation Level-Dependent Magnetic Resonance Imaging: A Sensitive and Objective Analysis.

The aim of this study was to determine a robust (sensitive and objective) method for analyzing renal blood oxygenation level-dependent magnetic resonance imaging data. Forty-seven subjects (30 with chronic kidney disease [CKD] and 17 controls) were imaged at baseline and after furosemide with a multiecho gradient recalled echo sequence. Conventional analysis consisted of regional segmentation (small cortex, large cortex, and medulla), followed by computing the mean of each region. In addition, we segmented the entire parenchyma and computed the mean (μ1) plus higher moments (μ2, μ3, and μ4). Two raters performed each of the segmentation steps, and agreement was assessed with intraclass correlation coefficients (ICCs). We used a measure of effect size (Cohen's d value), in addition to the usual measure of statistical significance, P values, for determining significant results. The mean of the renal parenchyma showed the highest agreement between raters (ICC, 0.99), and the higher parenchyma moments were on par with large cortical region of interest (ROI) ICC. The renal parenchymal mean also exhibited significant sensitivity to changes after furosemide administration in healthy subjects (P = 0.002, d = 0.84), in agreement with medullary ROIs (P = 0.002, d = 1.59). When comparing controls and subjects with CKD at baseline, cortical ROI showed a significant difference (P = 0.015, d = -0.69), whereas the parenchyma ROI did not (P = 0.152, d = 0.39). Post-furosemide data in all regions resulted in a significant difference (large cortex: P = 0.026, d = -0.51; medulla: P = 0.019, d = -0.61) with the renal parenchyma ROI resulting in the largest effect size (P = 0.003, d = -0.75). Higher moments of the renal parenchyma showed similar significant differences as well. Overall, our data support the use of the entire parenchyma to evaluate changes in the medulla after administration of furosemide, a widely used pharmacological maneuver. Changes in higher moments indicate that there is more than just a shift in the mean renal R2* and may provide clinically relevant information without the need for subjective regional segmentation. For evaluating differences between controls and subjects with CKD at baseline; large cortical ROI provided the highest sensitivity and objectivity. A combination of renal parenchyma assessment and large cortical ROI may provide the most robust method of evaluating renal blood oxygenation level-dependent magnetic resonance imaging data.

Potential role of the glycolytic oscillator in acute hypoxia in tumors

Tumor acute hypoxia has a dynamic component that is also, at least partially, coherent. Using blood oxygen level dependent magnetic resonance imaging, we observed coherent oscillations in hemoglobin saturation dynamics in cell line xenograft models of head and neck squamous cell carcinoma. We posit a well-established biochemical nonlinear oscillatory mechanism called the glycolytic oscillator as a potential cause of the coherent oscillations in tumors. These data suggest that metabolic changes within individual tumor cells may affect the local tumor microenvironment including oxygen availability and therefore radiosensitivity. These individual cells can synchronize the oscillations in patches of similar intermediate glucose levels. These alterations have potentially important implications for radiation therapy and are a potential target for optimizing the cancer response to radiation.

Abstract 9839: Beta Blockers Improve Renal Tissue Oxygenation in Hypertensive Patients Suspected of Renal Artery Stenosis

Background: Chronic renal hypoxia influences the progression of chronic kidney disease (CKD). Blood oxygen level dependent (BOLD) magnetic resonance (MR) is a noninvasive tool for assessment of renal tissue oxygenation. Beta blockers reduce cardiovascular mortality in patients with CKD and systolic heart failure, however the mechanisms of this benefit remain unclear. We sought to determine the association between beta blocker use, renal cortical and medullary oxygenation, and renal blood flow in hypertensive patients suspected of renal artery stenosis. Hypothesis: Chronic receipt of beta blockers will be associated with improved renal tissue oxygenation as assessed by BOLD MR. Methods: We measured renal cortical and medullary oxygenation using BOLD MR and renal artery blood flow using MR phase contrast techniques in 38 participants suspected of renal artery stenosis. Results: Chronic beta blocker therapy was associated with improved renal cortical (p=0.0007) and medullary (p=0.03) oxygenation (Figure). Receipt of angiotensin converting enzyme inhibitors or angiotensin receptor blockers was associated with reduced medullary oxygenation (p=0.01). In a multivariable model including gender, hemoglobin, diabetes, loop diuretic use, and mineralocorticoid use, chronic receipt of beta blockers was the only significant predictor of renal tissue oxygenation (β= 8.4, p=0.008). Conclusions: Beta blocker therapy was associated with improved renal oxygenation independent of renal blood flow suggesting may these findings may be related to reduced renal oxygen consumption. In addition to their known benefits to reduce cardiovascular mortality in patients with renal disease, beta blockers may reduce or prevent progression of renal dysfunction in patients with hypertension, diabetes, and renovascular disease. These observations may have important implications for treatment of patients with CKD.

Quantifying fluctuations of resting state networks using arterial spin labeling perfusion MRI

Blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) has been widely used to investigate spontaneous low-frequency signal fluctuations across brain resting state networks. However, BOLD only provides relative measures of signal fluctuations. Arterial Spin Labeling (ASL) MRI holds great potential for quantitative measurements of resting state network fluctuations. This study systematically quantified signal fluctuations of the large-scale resting state networks using ASL data from 20 healthy volunteers by separating them from global signal fluctuations and fluctuations caused by residual noise. Global ASL signal fluctuation was 7.59% ± 1.47% relative to the ASL baseline perfusion. Fluctuations of seven detected resting state networks vary from 2.96% ± 0.93% to 6.71% ± 2.35%. Fluctuations of networks and residual noise were 6.05% ± 1.18% and 6.78% ± 1.16% using 4-mm resolution ASL data applied with Gaussian smoothing kernel of 6mm. However, network fluctuations were reduced by 7.77% ± 1.56% while residual noise fluctuation was markedly reduced by 39.75% ± 2.90% when smoothing kernel of 12 mm was applied to the ASL data. Therefore, global and network fluctuations are the dominant structured noise sources in ASL data. Quantitative measurements of resting state networks may enable improved noise reduction and provide insights into the function of healthy and diseased brain.

A Functional Magnetic Resonance Imaging Study to Investigate the Utility of a Picture Imagination Task in Investigating Neural Responses in Patients with Chronic Musculoskeletal Pain to Daily Physical Activity Photographs

Pain-related anxiety and fear are associated with increased difficulties in attention, increased awareness of pain, impaired disengagement from pain, and can moderate the effects of attentional coping attempts. Accurately assessing the direct impact of pain-related anxiety and fear on pain behavior has proved difficult. Studies have demonstrated no or limited influence of pain-related fear and anxiety on behavior but this may be due to inherent problems with the scales used. Neuroimaging has improved the understanding of neural processes underlying the factors that influence pain perception. This study aimed to establish if a Picture and Imagination Task (PIT), largely developed from the Photographs of Daily Activity (PHODA) assessment tool, could help explore how people living with chronic pain process information about daily activities. Blood oxygenation level dependent (BOLD) functional magnetic resonance imaging (fMRI) was used to compare brain responses in patients with chronic musculoskeletal pain (CMSKP) (n = 15) and healthy controls (n = 15). Subjects were asked to imagine how they would feel mentally and physically if asked to perform daily activities illustrated in PIT. The results found that a number of regions involved in pain processing saw increased BOLD activation in patients compared with controls when undertaking the task and included the insula, anterior cingulate cortex, thalamus and inferior and superior parietal cortices. Similarly, increased BOLD responses in patients compared to controls in the frontal pole, paracingulate and the supplementary motor cortex may be suggestive of a memory component to the responses The amygdala, orbitofrontal cortex, substantia nigra/ventral tegmentum, putamen, thalamus, pallidum, inferior parietal (supramarginal and angular gyrus) and cingulate cortex were also seen to have greater differences in BOLD signal changes in patients compared with controls and many of these regions are also associated with general phobic responses. Therefore, we suggest that PIT is a useful task to explore pain- and movement-related anxiety and fear in fMRI studies. Regions in the Default Mode Network remained active or were less deactivated during the PIT task in patients with CMSKP compared to healthy controls supporting the contention that the DMN is abnormal in patients with CMSKP.

A hemodynamic model for layered BOLD signals

High-resolution blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) at the sub-millimeter scale has become feasible with recent advances in MR technology. In principle, this would enable the study of layered cortical circuits, one of the fundaments of cortical computation. However, the spatial layout of cortical blood supply may become an important confound at such high resolution. In particular, venous blood draining back to the cortical surface perpendicularly to the layered structure is expected to influence the measured responses in different layers. Here, we present an extension of a hemodynamic model commonly used for analyzing fMRI data (in dynamic causal models or biophysical network models) that accounts for such blood draining effects by coupling local hemodynamics across layers. We illustrate the properties of the model and its inversion by a series of simulations and show that it successfully captures layered fMRI data obtained during a simple visual experiment. We conclude that for future studies of the dynamics of layered neuronal circuits with high-resolution fMRI, it will be pivotal to include effects of blood draining, particularly when trying to infer on the layer-specific connections in cortex — a theme of key relevance for brain disorders like schizophrenia and for theories of brain function such as predictive coding.

Placental oxygen transport estimated by the hyperoxic placental BOLD MRI response.

Estimating placental oxygen transport capacity is highly desirable, as impaired placental function is associated with fetal growth restriction (FGR) and poor neonatal outcome. In clinical obstetrics, a noninvasive method to estimate the placental oxygen transport is not available, and the current methods focus on fetal well-being rather than on direct assessment of placental function. In this article, we aim to estimate the placental oxygen transport using the hyperoxic placental blood oxygen level-dependent (BOLD) magnetic resonance imaging (MRI) response. In 21 normal pregnancies and in four cases of severe early onset FGR, placental BOLD MRI was performed in a 1.5 Tesla MRI system (TR:8000 msec, TE:50 msec, Flip angle:90). Placental histological examination was performed in the FGR cases. In normal pregnancies, the average hyperoxic placental BOLD response was 12.6 ± 5.4% (mean ± SD). In the FGR cases, the hyperoxic BOLD response was abnormal only in cases with histological signs of maternal hypoperfusion of the placenta. The hyperoxic placental BOLD response is mainly derived from an increase in the saturation of maternal venous blood. In the normal placenta, the pO2 of the umbilical vein is closely related to the pO2 of the uterine vein. Therefore, the hyperoxic placental BOLD response may reflect the placental oxygen supply to the fetus. In early onset FGR, the placental oxygen transport is reduced mainly because of the maternal hypoperfusion, and in these cases the placental BOLD response might be altered. Thus, the placental BOLD MRI might provide direct noninvasive assessment of placental oxygen transport.

Brain Correlates of Self-Evaluation Deficits in Schizophrenia: A Combined Functional and Structural MRI Study.

Self-evaluation plays an important role in adaptive functioning and is a process that is typically impaired in patients with schizophrenia. Underlying neural mechanisms for this dysfunction may be associated with manifested psychosis. However, the brain substrates underlying this deficit are not well known. The present study used brain blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) and gray matter voxel-based morphometry to explore the functional and structural brain correlates of self-evaluation deficits in schizophrenia. Eighteen patients with schizophrenia and 17 healthy controls were recruited and asked to judge whether a set of personality-trait adjectives were appropriate for describing themselves, a familiar other, or whether the adjectives were of positive or negative valence. Patients had slower response times for negative trait attributions than controls did; responses to positive trait attributions were faster than those for negative traits among the patient group, while no differences were observed in the control group. Control subjects showed greater activation within the dorsal medial prefrontal cortex (dMPFC) and the anterior cingulate cortex (ACC) than the patient group during the self-evaluation > semantic positivity-evaluation contrast. Patients showed greater activation mainly within the posterior cingulate gyrus (PCC) as compared to controls for the other-evaluation > semantic positivity-evaluation contrast. Furthermore, gray matter volume was reduced in the MPFC, temporal lobe, cuneus, and the dorsal lateral prefrontal cortex (DLPFC) among the patient group when compared to controls. The present study adds to previous findings regarding self- and other-referential processing in schizophrenia, providing support for neurobiological models of self-reflection impairment.

Resting-state functional connectivity and nicotine addiction: prospects for biomarker development.

Given conceptual frameworks of addiction as a disease of intercommunicating brain networks, examinations of network interactions may provide a holistic characterization of addiction-related dysfunction. One such methodological approach is the examination of resting-state functional connectivity, which quantifies correlations in low-frequency fluctuations of the blood oxygen level-dependent magnetic resonance imaging signal between disparate brain regions in the absence of task performance. Here, evidence of differentiated effects of chronic nicotine exposure, which reduces the efficiency of network communication across the brain, and acute nicotine exposure, which increases connectivity within specific limbic circuits, is discussed. Several large-scale resting networks, including the salience, default, and executive control networks, have also been implicated in nicotine addiction. The dynamics of connectivity changes among and between these large-scale networks during nicotine withdrawal and satiety provide a heuristic framework with which to characterize the neurobiological mechanism of addiction. The ability to simultaneously quantify effects of both chronic (trait) and acute (state) nicotine exposure provides a platform to develop a neuroimaging-based addiction biomarker. While such development remains in its early stages, evidence of coherent modulations in resting-state functional connectivity at various stages of nicotine addiction suggests potential network interactions on which to focus future addiction biomarker development.

Sources of systematic error in calibrated BOLD based mapping of baseline oxygen extraction fraction

Recently a new class of calibrated blood oxygen level dependent (BOLD) functional magnetic resonance imaging (MRI) methods were introduced to quantitatively measure the baseline oxygen extraction fraction (OEF). These methods rely on two respiratory challenges and a mathematical model of the resultant changes in the BOLD functional MRI signal to estimate the OEF. However, this mathematical model does not include all of the effects that contribute to the BOLD signal, it relies on several physiological assumptions and it may be affected by intersubject physiological variability. The aim of this study was to investigate these sources of systematic error and their effect on estimating the OEF. This was achieved through simulation using a detailed model of the BOLD signal. Large ranges for intersubject variability in baseline physiological parameters such as haematocrit and cerebral blood volume were considered. Despite this the uncertainty in the relationship between the measured BOLD signals and the OEF was relatively low. Investigations of the physiological assumptions that underlie the mathematical model revealed that OEF measurements are likely to be overestimated if oxygen metabolism changes during hypercapnia or cerebral blood flow changes under hyperoxia. Hypoxic hypoxia was predicted to result in an underestimation of the OEF, whilst anaemic hypoxia was found to have only a minimal effect.

Carbogen gas-challenge blood oxygen level-dependent magnetic resonance imaging in hepatocellular carcinoma: Initial results.

The present study aimed to evaluate the feasibility of performing carbogen gas-challenge blood oxygen level-dependent (BOLD) magnetic resonance imaging (MRI) measurements in patients with hepatocellular carcinoma (HCC). A total of 25 patients with HCC underwent T2* mapping derived from multi-echo gradient-recalled echo imaging prior to and following breathing carbogen (95% O2 and 5% CO2) for 10 min. Follow-up T2* mapping was performed in 5 patients 1 day after transarterial chemoembolization (TACE). T2*, R2* and ∆R2* values (R2*air - R2*carb) of the whole tumor, the solid region of the tumor and the adjacent liver parenchyma were measured and compared in the patients with HCC. The T2* value of the solid region of the tumor following carbogen breathing was higher than the value following room air breathing (P<0.05), and the R2* value of room air breathing was higher than that following carbogen breathing (P<0.05). ∆R2* values of the tumor and the adjacent liver parenchyma prior to and following carbogen breathing were 2.4±7.8, 8.1±14.7 and 2.0±11.0 sec−1, respectively. R2* values were significantly decreased in 2 cases 1 day after TACE (17.8 vs. −3.4 sec−1 and 10.2 vs. 2.4 sec−1). Overall, carbogen gas-challenge BOLD MRI measurements are feasible in clinical settings and may serve as a novel functional biomarker for monitoring the treatment efficacy of embolic therapies for HCC.