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Purpose: To investigate the feasibility of using MRI based oxygenation imaging for early assessment of ischemic acute kidney injury (AKI) in an embolization model., Methods: Ischemic AKI model was induced in 40 rabbits by injection of microspheres into the right renal arteries. Animals were grouped according to the dose of microspheres: Severe AKI group, 2.0 mg (N = 10); Moderate AKI group, 1.0 mg (N = 10); Mild AKI group, 0.5 mg (N = 10); Control group, saline without microspheres (N = 10). A serial MRI examination was performed at intervals of 1 h, 1 day, 1 week and 4 weeks to evaluate the deterioration of renal function. A multi-echo ASE sequence was implemented for renal oxygenation measurement 1 h after surgery. Pathological examinations were performed 4 weeks after the surgery., Results: In renal cortex, renal oxygen extraction fraction (OEF) raised significantly after embolization procedures in all experimental groups (severe AKI: 0.39 ± 0.05, P < 0.05; moderate AKI: 0.36 ± 0.03, P < 0.05; mild AKI: 0.34 ± 0.02, P < 0.05) compared to the control group (0.29 ± 0.02). In outer medulla, significant difference was observed between control group (0.29 ± 0.03) and severe AKI group (0.35 ± 0.03, P < 0.05), and between control group and moderate AKI group (0.34 ± 0.04, P < 0.05). Corresponding lesions were found in pathological examinations 4 weeks after the procedure., Conclusion: This study demonstrates the feasibility of using oxygenation imaging to assess the embolization induced ischemic AKI at an early stage., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: To compare gradient echo (GRE) and gradient echo sampling of spin echo (GESSE) sequences for the quantification of the oxygen extraction fraction (OEF) from combined quantitative BOLD and quantitative susceptibility mapping (QSM) with regard to accuracy, precision and parameter initialization., Methods: GRE and GESSE data were acquired from 7 healthy volunteers. QSM was applied to the GRE data and used as a regularization for the single-compartment quantitative BOLD fit to the GESSE and GRE data, respectively, to quantify OEF, deoxygenated blood volume (ν), R 2 , and non-blood susceptibility (χ nb ). Intersubject means within gray and white matter, respectively, were compared between GESSE and GRE (Student's t) and gray-white matter contrast was determined for each sequence separately. A single- and multi-compartment simulation was used to compare reconstruction accuracy., Results: Intersubject means and SDs for gray and white matter were OEF = 32.4 ± 1.6%, ν = 2.9 ± 0.1%, R 2 = 14.2 ± 0.5 Hz, χ nb = -43 ± 5 ppb for GESSE and OEF = 43.0 ± 5.4%, ν = 3.5 ± 0.4%, R 2 = 14.4 ± 0.7 Hz, χ nb = -43 ± 8 ppb for GRE with a significant difference (P < 0.05) for OEF and ν. Gray-white matter contrast was significant (P < 0.05) in all parameters for GESSE but only in ν and R 2 for GRE. All parameters reconstructed from GESSE had higher accuracy than from GRE in the single- but not multi-compartment simulation., Conclusion: GESSE yields higher parameter accuracy in simulated gray matter but produces unphysiological gray-white matter contrast in OEF in vivo. GRE produces uniform OEF maps in vivo and is more efficient, which could facilitate a clinical implementation, but revealed biases in simulation. The appropriate sequence should be chosen depending on application., (© 2019 International Society for Magnetic Resonance in Medicine.)

Purpose: T 2 -relaxation-under-spin-tagging (TRUST) is an MR technique for the non-invasive assessment of whole-brain cerebral oxygen extraction fraction (OEF), through measurement of the venous blood T 2 relaxation time in the sagittal sinus. A key limitation of TRUST, however, is the lack of spatial specificity of the measurement. We sought to develop a modified TRUST sequence, selective localized TRUST (SL-TRUST), having sensitivity to venous blood T 2 within a targeted brain region, and therefore achieving spatially localized measurements of cerebral tissue OEF, while still retaining acquisition in the sagittal sinus., Methods: A method for selective localization of TRUST sequence was developed, and the reproducibility of the technique was evaluated in healthy participants. Regional measurements were achieved for a single hemisphere and for a 3D-localized 70 × 70 × 80 mm 3 tissue region using SL-TRUST and compared to a global TRUST measure. An additional measure of venous blood T 1 in the sagittal sinus was used to estimate subject-specific hematocrit. Six subjects were scanned over 4 sessions, including intra-session repeat measurements., Results: The average T 2 in the sagittal sinus was found to be 60.8 ± 8.9, 62.7 ± 7.9, 64.6 ± 8.4, and 66.3 ± 10.3 ms (mean ± SD) for conventional TRUST, global SL-TRUST, hemispheric SL-TRUST, and 3D-localized SL-TRUST, respectively. Intra-, inter-session, and inter-subject coefficients of variation for OEF using SL-TRUST were found to be comparable and in some cases superior to those obtained using TRUST., Conclusion: OEF comparison of 2 contralateral regions was achievable in under 5 min suggesting SL-TRUST offers potential for quantifying regional OEF differences in both healthy and clinical populations., (© 2019 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society forMagnetic Resonance in Medicine.)

It is well-established that patients with sickle cell disease (SCD) are at substantial risk of neurological complications, including overt and silent stroke, microstructural injury, and cognitive difficulties. Yet the underlying mechanisms remain poorly understood, partly because findings have largely been considered in isolation. Here, we review mechanistic pathways for which there is accumulating evidence and propose an integrative systems-biology framework for understanding neurological risk. Drawing upon work from other vascular beds in SCD, as well as the wider stroke literature, we propose that macro-circulatory hyper-perfusion, regions of relative micro-circulatory hypo-perfusion, and an exhaustion of cerebral reserve mechanisms, together lead to a state of cerebral vascular instability. We suggest that in this state, tissue oxygen supply is fragile and easily perturbed by changes in clinical condition, with the potential for stroke and/or microstructural injury if metabolic demand exceeds tissue oxygenation. This framework brings together recent developments in the field, highlights outstanding questions, and offers a first step toward a linking pathophysiological explanation of neurological risk that may help inform future screening and treatment strategies.

The purposes of this study are to assess the oxygen extraction fraction (OEF) changes on MRI-based quantitative susceptibility mapping (QSM) in systemic lupus erythematosus (SLE) patients and to determine whether QSM-OEF is associated with disease activity in SLE. We enrolled 42 SLE patients and 20 healthy subjects (HS) who had no pathologies on conventional brain MRI. Disease activity was assessed using SLE Disease Activity Index (SLEDAI). For the measurement of QSM-OEF, QSM data were analysed using the Perfusion Mismatch Analyzer software program. Spearman's or Pearson's correlation coefficients were calculated, and independent predictors were identified through a multiple linear regression analysis. QSM-OEF was significantly higher in SLE than that in HS (51.3 ± 10.1 vs. 40.5 ± 3.7, p  < 0.001). QSM-OEF was positively correlated with SLEDAI and the presence of neuropsychiatric symptom (NPS) scores (ρ = 0.663, p  < 0.001 and ρ = 0.340, p  = 0.028). At multiple linear regression analysis, SLEDAI and NPS were independently associated with QSM-OEF (standardized β = 0.426, p  = 0.016 and standardized β = 6.148, p  = 0.029). In the SLE patients, QSM-OEF is associated with disease activity, which might predict an increased risk of stroke in SLE.

There is increasing interest in applying physiological MRI in neonates, based on the premise that physiological parameters may provide an early biomarker of neonatal brain health and injury. Two commonly used techniques are oxygen extraction fraction (OEF) measurement using T 2 -relaxation-under-spin-tagging (TRUST) MRI and cerebral blood flow measurement using phase-contrast (PC) quantitative flow MRI, which collectively provide an assessment of the brain's oxygen consumption. However, prior research has only demonstrated proof of principle of these methods in neonates, without characterization or benchmarking of the techniques. This is because available time is limited in neonatal subjects, especially when scans are performed as add-ons to clinical scans (typically less than 5 min). The work presented aims to examine the TRUST and PC MRI sequences systematically in normal neonates, through research-dedicated scan sessions. A series of characterization and optimization studies were conducted in a total of 26 radiographically normal neonates on 3 T systems. Our results show that TRUST MRI at the superior sagittal sinus (SSS) provides an OEF measurement equivalent to that at the internal jugular vein (r = 0.80, n = 10), yet with shorter scan time. Lower resolution provided better precision in the TRUST measurement (p = 0.001, n = 9). Therefore, the preferred OEF measurement is to apply TRUST MRI at the SSS using a spatial resolution of 2.5 mm. For PC MRI, our results showed that non-gated PC MRI yielded blood flow measurements comparable to those from the more time-consuming gated approach in neonates (r = 0.89, n = 7). It was also found that blood flow could be overestimated by 18% when imaging resolution is larger than 0.3 mm (n = 7). Therefore, non-gated PC MRI with a spatial resolution of 0.3 mm is recommended for neonatal applications. In conclusion, this study verifies consistency of neonatal brain oxygenation and flow measurements across acquisition schemes and points to optimal strategies in parameter selection when using these sequences., (© 2019 John Wiley & Sons, Ltd.)

The goal of the present study was to examine the cerebral metabolism and vascular reactivity during extended breath-holds (ranging from 2 min 32 s to 7 min 0 s) and during a hypoxic challenge in freedivers and non-diver controls. Magnetic resonance imaging was used to measure the global cerebral blood flow (CBF) and metabolic rate of oxygen (CMRO 2 ), and magnetic resonance spectroscopy was used to measure the cerebral lactate, glutamate+glutamine, N-acetylaspartate and phosphocreatine+creatine concentrations in the occipital lobe. Fifteen freedivers and seventeen non-diver controls participated. The freedivers showed remarkable increases in CBF (107%) during the breath-holds, compensating for arterial desaturation, and sustained cerebral oxygen delivery (CDO 2 ). CMRO 2 was unaffected throughout the breath-holds. During the hypoxic challenge, the freedivers had larger increases in blood flow in the sagittal sinus than the non-divers, and could sustain normal CDO 2 . No differences were found in lactate production, global CBF or CMRO 2 . We conclude that the mechanism for sustaining brain function during breath-holding in freedivers involves an extraordinary increase in perfusion, and that freedivers present evidence for higher cerebrovascular reactivity, but not for higher lactate-producing glycolysis during a hypoxic challenge compared to controls.

Background: Blood transfusions are administered to children and adults with sickle cell anemia (SCA) for secondary stroke prevention, or as treatment for recurrent pain crises or acute anemia, but transfusion effects on cerebral hemodynamics and metabolism are not well-characterized., Purpose: To compare blood transfusion-induced changes in hemometabolic parameters, including oxygen extraction fraction (OEF) and cerebral blood flow (CBF), within and between adults and children with SCA., Study Type: Prospective, longitudinal study., Subjects: Adults with SCA (n = 16) receiving simple (n = 7) or exchange (n = 9) transfusions and children with SCA (n = 11) receiving exchange transfusions were scanned once when hematocrit was near nadir and again within 7 days of transfusion. Adult controls without SCA or sickle trait (n = 7) were scanned twice on separate days., Field Strength/sequence: 3.0T T 1 -weighted, T 2 -weighted, and T 2 -relaxation-under-spin-tagging (TRUST) imaging, and phase contrast angiography., Assessment: Global OEF was computed as the relative difference between venous oxygenation (from TRUST) and arterial oxygenation (from pulse oximetry). Global CBF was computed as total blood flow to the brain normalized by intracranial tissue volume., Statistical Tests: Hemometabolic variables were compared using two-sided Wilcoxon signed-rank tests; associations were analyzed using two-sided Spearman's correlation testing., Results: In adults with SCA, posttransfusion OEF = 0.38 ± 0.05 was lower (P = 0.001) than pretransfusion OEF = 0.45 ± 0.09. A change in OEF was correlated with increases in hematocrit (P = 0.02; rho = -0.62) and with pretransfusion hematocrit (P = 0.02; rho = 0.65). OEF changes after transfusion were greater (P = 0.002) in adults receiving simple versus exchange transfusions. Posttransfusion CBF = 77.7 ± 26.4 ml/100g/min was not different (P = 0.27) from pretransfusion CBF = 82.3 ± 30.2 ml/100g/min. In children with SCA, both posttransfusion OEF = 0.28 ± 0.04 and CBF = 76.4 ± 26.4 were lower than pretransfusion OEF = 0.36 ± 0.06 (P = 0.004) and CBF = 96.4 ± 16.5 (P = 0.004)., Data Conclusion: Cerebral OEF reduces following transfusions in adults and children with SCA. CBF reduces following transfusions more often in children compared to adults, indicating that vascular reserve capacity may remain near exhaustion posttransfusion in many adults., Level of Evidence: 2 Technical Efficacy Stage 5 J. Magn. Reson. Imaging 2019;49:466-477., (© 2018 International Society for Magnetic Resonance in Medicine.)

Background: Diffuse correlation spectroscopy (DCS) noninvasively permits continuous, quantitative, bedside measurements of cerebral blood flow (CBF). To test whether optical monitoring (OM) can detect decrements in CBF producing cerebral hypoxia, we applied the OM technique continuously to probe brain-injured patients who also had invasive brain tissue oxygen (PbO 2 ) monitors., Methods: Comatose patients with a Glasgow Coma Score (GCS) < 8) were enrolled in an IRB-approved protocol after obtaining informed consent from the legally authorized representative. Patients underwent 6-8 h of daily monitoring. Brain PbO 2 was measured with a Clark electrode. Absolute CBF was monitored with DCS, calibrated by perfusion measurements based on intravenous indocyanine green bolus administration. Variation of optical CBF and mean arterial pressure (MAP) from baseline was measured during periods of brain hypoxia (defined as a drop in PbO 2 below 19 mmHg for more than 6 min from baseline (PbO 2  > 21 mmHg). In a secondary analysis, we compared optical CBF and MAP during randomly selected 12-min periods of "normal" (> 21 mmHg) and "low" (< 19 mmHg) PbO 2 . Receiver operator characteristic (ROC) and logistic regression analysis were employed to assess the utility of optical CBF, MAP, and the two-variable combination, for discrimination of brain hypoxia from normal brain oxygen tension., Results: Seven patients were enrolled and monitored for a total of 17 days. Baseline-normalized MAP and CBF significantly decreased during brain hypoxia events (p < 0.05). Through use of randomly selected, temporally sparse windows of low and high PbO 2 , we observed that both MAP and optical CBF discriminated between periods of brain hypoxia and normal brain oxygen tension (ROC AUC 0.761, 0.762, respectively). Further, combining these variables using logistic regression analysis markedly improved the ability to distinguish low- and high-PbO 2 epochs (AUC 0.876)., Conclusions: The data suggest optical techniques may be able to provide continuous individualized CBF measurement to indicate occurrence of brain hypoxia and guide brain-directed therapy.

In 2001 Raichle and colleagues showed that, at rest, brain activity fluctuates near a metabolically active equilibrium: a 'default mode' of brain function. This finding broke ranks with the prevailing 'task-rest' dichotomy to position the brain as continuously active, balancing the deployment of resources according to current and anticipated needs., (Crown Copyright © 2018. Published by Elsevier Ltd. All rights reserved.)

CBF, OEF, and CMRO 2 images can be quantitatively assessed using PET. Their image calculation requires arterial input functions, which require invasive procedure. The aim of the present study was to develop a non-invasive approach with image-derived input functions (IDIFs) using an image from an ultra-rapid O 2 and C 15 O 2 protocol. Our technique consists of using a formula to express the input using tissue curve with rate constants. For multiple tissue curves, the rate constants were estimated so as to minimize the differences of the inputs using the multiple tissue curves. The estimated rates were used to express the inputs and the mean of the estimated inputs was used as an IDIF. The method was tested in human subjects ( n = 24). The estimated IDIFs were well-reproduced against the measured ones. The difference in the calculated CBF, OEF, and CMRO 2 values by the two methods was small (<10%) against the invasive method, and the values showed tight correlations ( r = 0.97). The simulation showed errors associated with the assumed parameters were less than ∼10%. Our results demonstrate that IDIFs can be reconstructed from tissue curves, suggesting the possibility of using a non-invasive technique to assess CBF, OEF, and CMRO 2 .

The effect of cerebral amyloidosis on cerebral hemodynamics was investigated with photoacoustic tomography (PAT) and magnetic resonance imaging (MRI). First, the sensitivity and robustness of PAT for deriving metrics of vascular and tissue oxygenation in the murine brain was assessed in wild-type mice with a hyperoxia-normoxia challenge. Secondly, cerebral oxygenation was assessed in young and aged arcAβ mice and wild-type controls with PAT, while cerebral blood flow (CBF) was determined by perfusion MRI. The investigations revealed that PAT can sensitively and robustly detect physiological changes in vascular and tissue oxygenation. An advanced stage of cerebral amyloidosis in arcAβ mice is accompanied by a decreases in cortical CBF and the cerebral metabolic rate of oxygen (CMRO 2 ), as oxygen extraction fraction (OEF) has been found unaffected. Thus, PAT constitutes a robust non-invasive tool for deriving metrics of tissue oxygenation, extraction and metabolism in the mouse brain under physiological and disease states.

Calibrated fMRI based on arterial spin-labeling (ASL) and blood oxygen-dependent contrast (BOLD), combined with periods of hypercapnia and hyperoxia, can provide information on cerebrovascular reactivity (CVR), resting blood flow (CBF), oxygen extraction fraction (OEF), and resting oxidative metabolism (CMRO 2 ). Vascular and metabolic integrity are believed to be affected in Alzheimer's disease (AD), thus, the use of calibrated fMRI in AD may help understand the disease and monitor therapeutic responses in future clinical trials. In the present work, we applied a calibrated fMRI approach referred to as Quantitative O2 (QUO2) in a cohort of probable AD dementia and age-matched control participants. The resulting CBF, OEF and CMRO 2 values fell within the range from previous studies using positron emission tomography (PET) with 15 O labeling. Moreover, the typical parietotemporal pattern of hypoperfusion and hypometabolism in AD was observed, especially in the precuneus, a particularly vulnerable region. We detected no deficit in frontal CBF, nor in whole grey matter CVR, which supports the hypothesis that the effects observed were associated specifically with AD rather than generalized vascular disease. Some key pitfalls affecting both ASL and BOLD methods were encountered, such as prolonged arterial transit times (particularly in the occipital lobe), the presence of susceptibility artifacts obscuring medial temporal regions, and the challenges associated with the hypercapnic manipulation in AD patients and elderly participants. The present results are encouraging and demonstrate the promise of calibrated fMRI measurements as potential biomarkers in AD. Although CMRO 2 can be imaged with 15 O PET, the QUO2 method uses more widely available imaging infrastructure, avoids exposure to ionizing radiation, and integrates with other MRI-based measures of brain structure and function.

Purpose: Quantitative susceptibility mapping (QSM) enables cerebral venous characterization and physiological measurements, such as oxygen extraction fraction (OEF). The exquisite sensitivity of QSM to deoxygenated blood makes it possible to image small veins; however partial volume effects must be addressed for accurate quantification. We present a new method, Iterative Cylindrical Fitting (ICF), to estimate voxel-based partial volume effects for susceptibility maps and use it to improve OEF quantification of small veins with diameters between 1.5 and 4 voxels. Materials and Methods: Simulated QSM maps were generated to assess the performance of the ICF method over a range of vein geometries with varying echo times and noise levels. The ICF method was also applied to in vivo human brain data to assess the feasibility and behavior of OEF measurements compared to the maximum intensity voxel (MIV) method. Results: Improved quantification of OEF measurements was achieved for vessels with contrast to noise greater than 3.0 and vein radii greater than 0.75 voxels. The ICF method produced improved quantitative accuracy of OEF measurement compared to the MIV approach (mean OEF error 7.7 vs. 12.4%). The ICF method provided estimates of vein radius (mean error <27%) and partial volume maps (root mean-squared error <13%). In vivo results demonstrated consistent estimates of OEF along vein segments. Conclusion: OEF quantification in small veins (1.5-4 voxels in diameter) had lower error when using partial volume estimates from the ICF method.

The purposes of this study are to establish oxygen extraction fraction (OEF) measurements using quantitative susceptibility mapping (QSM) of magnetic resonance imaging (MRI), and to compare QSM-OEF data with the gold standard (15)O positron emission tomography (PET). Twenty-six patients with chronic unilateral internal carotid artery or middle cerebral artery stenosis or occlusion, and 15 normal subjects were included. MRI scans were conducted using a 3.0 Tesla scanner with a three-dimensional spoiled gradient recalled sequence. QSM images were created using the morphology-enabled dipole inversion method, and OEF maps were generated from QSM images using extraction of venous susceptibility induced by deoxygenated hemoglobin. Significant correlation of relative OEF ratio to contra-lateral hemisphere between QSM-OEF and PET-OEF was observed (r = 0.62, p < 0.001). The local (intra-section) correlation was also significant (r = 0.52, p < 0.001) in patients with increased PET-OEF. The sensitivity and specificity of OEF increase in QSM was 0.63 (5/8) and 0.89 (16/18), respectively, in comparison with PET. In conclusion, good correlation was achieved between QSM-OEF and PET-OEF in the identification of elevated OEF in affected hemispheres of patients with unilateral chronic steno-occlusive disease., (© The Author(s) 2015.)

Background: The aim of the present study is the characterization of hemodynamics to predict hyperperfusion syndrome (HPS) after carotid artery stenting (CAS) with positron emission tomography (PET) obtained before and on the first day after the treatment. Methods: Cerebral perfusion and oxygen metabolism were evaluated by 15O-gas PET in 18 patients with symptomatic internal carotid artery (ICA) stenosis before and on the first day after CAS. Regional cerebral blood flow (CBF), oxygen extraction fraction (OEF), cerebral metabolic rate of oxygen (CMRO2), and cerebral blood volume (CBV) were measured in the ipsilateral and contralateral middle cerebral artery territories and compared between before and after CAS. Results: CBF increased in 16 of 18 patients on the first day after CAS and postoperative CBF was significantly higher than preoperative CBF bilaterally. OEF decreased in 15 of 18 patients on the first day after CAS and postoperative OEF was significantly lower than preoperative OEF in the ipsilateral hemisphere. CMRO2 and CBV did not change significantly. None of the patients showed HPS after CAS. All patients who had preoperative OEF of 53% or more (misery perfusion) in the ipsilateral hemisphere showed 50% or more increase in CBF postoperatively. The preoperative OEF value significantly correlated with the rate of postoperative increase in CBF bilaterally. Conclusions: CAS increases cerebral perfusion and improves hemodynamic compromise in patients with symptomatic ICA stenosis. Although we could not clarify the usefulness of PET before and on the first day after CAS in predicting HPS, a high preoperative OEF is related to postoperative marked CBF increase and might be used as a predictor of HPS. Patients with greater hemodynamic compromise with a high preoperative OEF should be managed carefully to prevent HPS, but they have a greater chance of CBF increase after CAS. [Copyright &y& Elsevier]

Purpose: Develop an MRI method to estimate skeletal muscle oxygen consumption (VO2 ) with dynamic exercise using simultaneous measurement of venous blood flow (VBF) and venous oxygen saturation (SvO2 )., Methods: Real-time imaging of femoral VBF using a complex-difference method was interleaved with imaging of venous hemoglobin oxygen saturation (SvO2 ) using magnetic susceptometry to estimate muscle VO2 (Fick principle). Nine healthy subjects performed repeated 5-watt knee-extension (quadriceps) exercise within the bore of a 1.5 Tesla MRI scanner, for test/re-test comparison. VBF, SvO2 , and derived VO2 were estimated at baseline and immediately (<1 s) postexercise and every 2.4 s for 4 min., Results: Quadriceps muscle mass was 2.43 ± 0.31 kg. Mean baseline values were VBF = 0.13 ± 0.06 L/min/kg, SvO2 = 69.4 ± 10.1%, and VO2 = 6.8 ± 4.1 mL/min/kg. VBF, SvO2 , and VO2 values from peak exercise had good agreement between trials (VBF = 0.9 ± 0.1 versus 1.0 ± 0.1 L/min/kg, R(2) = 0.83, CV = 7.6%; SvO2 = 43.2 ± 13.5 versus 40.9 ± 13.1%, R(2) = 0.88, CV = 15.6%; VO2 = 95.7 ± 18.0 versus 108.9 ± 17.3 mL/min/kg, R(2) = 0.88, CV = 12.3%), as did the VO2 recovery time constant (26.1 ± 3.5 versus 26.0 ± 4.0 s, R(2) = 0.85, CV = 6.0%). CV = coefficient of variation., Conclusion: Rapid imaging of VBF and SvO2 for the estimation of whole muscle VO2 is compatible with dynamic exercise for the estimation of peak values and recovery dynamics following exercise with good reproducibility., (© 2014 Wiley Periodicals, Inc.)

Purpose: Oxygen extraction fraction (OEF), defined by the ratio of oxygen metabolism (MO2) to delivery (DO2), determines the level of compensation of MO2 by DO2. In the current study, we tested the hypothesis that inner retinal OEF remains unchanged during light flicker under systemic normoxia and hypoxia in rats due to the matching of MO2 and DO2., Methods: Retinal vascular oxygen tension (PO2) measurements were obtained in 10 rats by phosphorescence lifetime imaging. Inner retinal OEF was derived from vascular PO2 based on Fick's principle. Measurements were obtained before and during light flicker under systemic normoxia and hypoxia. The effects of light flicker and systemic oxygenation on retinal vascular PO2 and OEF were determined by ANOVA., Results: During light flicker, retinal venous PO2 decreased (P < 0.01, N = 10), while inner retinal OEF increased (P = 0.02). Under hypoxia, retinal arterial and venous PO2 decreased (P < 0.01), while OEF increased (P < 0.01). The interaction effect was not significant on OEF (P = 0.52), indicating the responses of OEF to light flicker were similar under normoxia and hypoxia. During light flicker, OEF increased from 0.46 ± 0.13 to 0.50 ± 0.11 under normoxia, while under hypoxia, OEF increased from 0.67 ± 0.16 to 0.74 ± 0.14., Conclusions: Inner retinal OEF increased during light flicker, indicating the relative change in DO2 is less than that in MO2 in rats under systemic normoxia and hypoxia. Inner retinal OEF is a potentially useful parameter for assessment of the relative changes of MO2 and DO2 under physiologic and pathologic conditions., (Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.)

Oxygen extraction fraction (OEF) is defined as the ratio of blood oxygen that a tissue takes from the blood flow to maintain function and morphological integrity. OEF reflects the efficiency of oxygen utilization by the tissue and, therefore, is a hemodynamic measure in brain ischemia. Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) is a common mitochondrial disorder. It is characterized by neurological remissions and relapses and associated with progressive neurocognitive deficits. Because of abnormalities of mitochondrial function in MELAS, defects in the oxidative metabolic pathways of energy production decrease the cerebral oxygen utilization and lead to the reduction of OEF. Quantification of OEF can reflect the functional status of cerebral mitochondria and provide insight into the pathophysiological changes in the brain in MELAS. In light of recent advances in MRI, the discovery of the blood-oxygen level-dependent signal has allowed development of MRI methods targeted toward quantitative OEF imaging. A new MR sequence, termed the gradient-echo sampling of spin echo, was successfully developed to enable quantitative assessment of the OEF in the brain tissue. MR OEF imaging in patients with MELAS detects extensive OEF reduction in the stroke-like lesions, as well as in the normal-appearing brain regions. More severe dysfunction of the mitochondria in the stroke-like lesions was implied at the onset of the stroke-like episode. Determination of OEF throughout the episode demonstrated a chronological change in mitochondrial function in individual cases. Such neuroimaging findings might provide some clues in the investigation of the underlying mechanisms of stroke-like episodes.

Aim: To review the literature on the assessment of venous vessels to estimate the penumbra on T2*w imaging and susceptibility-weighted imaging (SWI)., Methods: Literature that reported on the assessment of penumbra by T2*w imaging or SWI and used a validation method was included. PubMed and relevant stroke and magnetic resonance imaging (MRI) related conference abstracts were searched. Abstracts that had overlapping content with full text articles were excluded. The retrieved literature was scanned for further relevant references. Only clinical literature published in English was considered, patients with Moya-Moya syndrome were disregarded. Data is given as cumulative absolute and relative values, ranges are given where appropriate., Results: Forty-three publications including 1145 patients could be identified. T2*w imaging was used in 16 publications (627 patients), SWI in 26 publications (453 patients). Only one publication used both (65 patients). The cumulative presence of hypointense vessel sign was 54% (range 32%-100%) for T2* (668 patients) and 81% (range 34%-100%) for SWI (334 patients). There was rare mentioning of interrater agreement (6 publications, 210 patients) and reliability (1 publication, 20 patients) but the numbers reported ranged from good to excellent. In most publications (n = 22) perfusion MRI was used as a validation method (617 patients). More patients were scanned in the subacute than in the acute phase (596 patients vs 320 patients). Clinical outcome was reported in 13 publications (521 patients) but was not consistent., Conclusion: The low presence of vessels signs on T2*w imaging makes SWI much more promising. More research is needed to obtain formal validation and quantification.

Cerebral oxygen metabolism plays a critical role in maintaining normal function of the brain. It is the primary energy source to sustain neuronal functions. Abnormalities in oxygen metabolism occur in various neuro-pathologic conditions such as ischemic stroke, cerebral trauma, cancer, Alzheimer's disease and shock. Therefore, the ability to quantitatively measure tissue oxygenation and oxygen metabolism is essential to the understanding of pathophysiology and treatment of various diseases. The focus of this review is to provide an introduction of various blood oxygenation level dependent (BOLD) contrast methods for absolute measurements of tissue oxygenation, including both magnitude and phase image based approaches. The advantages and disadvantages of each method are discussed.