Oxygen extraction efficiency of the tidally-ventilated rectal gills of dragonfly nymphs.

Dragonfly nymphs breathe water using tidal ventilation, a highly unusual strategy in water-breathing animals owing to the high viscosity, density and low oxygen (O2) concentration of water. This study examines how well these insects extract O2 from the surrounding water during progressive hypoxia. Nymphs were attached to a custom-designed respiro-spirometer to simultaneously measure tidal volume, ventilation frequency and metabolic rate. Oxygen extraction efficiencies (OEE) were calculated across four partial pressure of oxygen (pO2) treatments, from normoxia to severe hypoxia. While there was no significant change in tidal volume, ventilation frequency increased significantly from 9.4 ± 1.2 breaths per minute (BPM) at 21.3 kPa to 35.6 ± 2.9 BPM at 5.3 kPa. Metabolic rate increased significantly from 1.4 ± 0.3 µl O2 min-1 at 21.3 kPa to 2.1 ± 0.4 µl O2 min-1 at 16.0 kPa, but then returned to normoxic levels as O2 levels declined further. OEE of nymphs was 40.1 ± 6.1% at 21.3 kPa, and did not change significantly during hypoxia. Comparison to literature shows that nymphs maintain their OEE during hypoxia unlike other aquatic tidal-breathers and some unidirectional breathers. This result, and numerical models simulating experimental conditions, indicate that nymphs maintain these extraction efficiencies by increasing gill conductance and/or lowering internal pO2 to maintain a sufficient diffusion gradient across their respiratory surface.

Quantitative BOLD (qBOLD) imaging of oxygen metabolism and blood oxygenation in the human body: A scoping review.

PURPOSE: There are many approaches to the quantitative BOLD (qBOLD) technique described in the literature, differing in pulse sequences, MRI parameters and data processing. Thus, in this review, we summarized the acquisition methods, approaches used for oxygenation quantification and clinical populations investigated. METHODS: Three databases were systematically searched (Medline, Embase, and Web of Science) for published research that used qBOLD methods for quantification of oxygen metabolism. Data extraction and synthesis were performed by one author and reviewed by a second author. RESULTS: A total of 93 relevant papers were identified. Acquisition strategies were summarized, and oxygenation parameters were found to have been investigated in many pathologies such as steno-occlusive diseases, stroke, glioma, and multiple sclerosis disease. CONCLUSION: A summary of qBOLD approaches for oxygenation measurements and applications could help researchers to identify good practice and provide objective information to inform the development of future consensus recommendations.

Quantitative 17 O MRSI of myocardial oxygen metabolic rate, blood flow, and oxygen extraction fraction under normal and high workload conditions.

PURPOSE: The heart is a highly aerobic organ consuming most of the oxygen the body in supporting heart function. Quantitative imaging of myocardial oxygen metabolism and perfusion is essential for studying cardiac physiopathology in vivo. Here, we report a new imaging method that can simultaneously assess myocardial oxygen metabolism and blood flow in the rat heart. METHODS: This novel method is based on the 17 O-MRSI combined with brief inhalation of 17 O-isotope labeled oxygen gas for quantitative imaging of myocardial metabolic rate of oxygen consumption (MVO2 ), myocardial blood flow (MBF), and oxygen extraction fraction (OEF). We demonstrate this imaging method under basal and high workload conditions in rat hearts at 9.4 T. RESULTS: We show that this 17 O MRSI-based approach can directly measure and image MVO2 (1.35-4.06 µmol/g/min), MBF (0.49-1.38 mL/g/min), and OEF (0.33-0.44) in the heart of anesthetized rat under basal and high workload (21.6 × 103 -56.7 × 103 mmHg • bpm) conditions. Under high workload condition, MVO2 and MBF values in healthy rats approximately doubled, whereas OEF remained unchanged, indicating a strong coupling between myocardial oxygen metabolic demand and supply through blood perfusion. CONCLUSION: The 17 O-MRSI method has been used to simultaneously image the myocardial metabolic rate of oxygen consumption, blood flow, and oxygen extraction fraction in small animal hearts, which are sensitive to the physiological changes induced by high workload. This approach could provide comprehensive measures that are critical for studying myocardial function in normal and diseased states and has a potential for translation.

Cerebral fractional tissue oxygen extraction (cFTOE) during immediate fetal-to-neonatal transition: a systematic qualitative review of the literature.

Cerebral monitoring during immediate fetal-to-neonatal transition is of increasing interest. The cerebral fractional tissue oxygen extraction (cFTOE) is a useful parameter to gain insight in the balance between tissue oxygen delivery and consumption during this complex process. The aim of this study was to review the literature on cFTOE during the first 15 min immediately after birth. A systematic qualitative literature research was last performed on 23 November 2023 of PubMed and EMBASE with the following search terms: neonate, infant, newborn, transition, after birth, delivery room, NIRS, near-infrared spectroscopy, spectroscopy, cFTOE, cerebral fractional tissue oxygenation extraction, cerebral oxygenation, and fractional oxygen extraction. Additional published reports were identified through a manual search of references in retrieved articles and in review articles. The methodological quality of the included studies was assessed by predefined quality criteria. Only human studies with data of cFTOE in the first 15 min after birth were included. Accordingly, exclusion criteria were defined as no measurement of cFTOE or no measurement within the first 15 min after birth. Across all studies, a total of 3566 infants (2423 term, 1143 preterm infants) were analysed. Twenty-five studies were identified describing cFTOE within the first 15 min after birth. Four studies established reference ranges for cFTOE and another four studies focused on the effect of pre-/perinatal circumstances on cFTOE in the first 15 min after birth. Six studies investigated the course of cFTOE after transition in infants without complications. Eleven studies analysed different potentially influencing parameters on cFTOE during transition. CONCLUSION: This systematic review provides a comprehensive insight on cFTOE during uncomplicated transition as well as the influence of perinatal circumstances, respiratory, haemodynamic, neurological, and laboratory parameters in preterm and term infants. WHAT IS KNOWN: • The NIRS-measured cerebral fractional tissue oxygen extraction (cFTOE) is a useful parameter to estimate the balance between oxygen delivery and consumption. • During normal transition, the cFTOE decreases in the first minutes after birth and then remains at a stable plateau. WHAT IS NEW: • The cFTOE is a promising parameter that gives additional information on cerebral oxygenation and perfusion in preterm and term infants. • Several hemodynamic, metabolic, respiratory, and perinatal factors are identified, influencing the oxygen extraction of the newborn's brain after birth.

Oxygen extraction fraction (OEF) values and applications in neurological diseases.

One of the goals of this systematic review is to provide a meta-analysis-derived mean OEF of healthy volunteers. Another aim of this study is to indicate the OEF ranges of various neurological pathologies. Potential clinical applications of OEF metrics are presented. Peer-reviewed studies reporting OEF metrics derived from computed tomography (CT)/positron emission tomography (PET) and/or magnetic resonance imaging (MRI) were considered. Databases utilized included MEDLINE, PubMed, EMBASE, Web of Science, and Google Scholar. The Newcastle-Ottawa scoring system was used for evaluating studies. R Studio was utilized for the meta-analysis calculations when appropriate. The GRADE framework was utilized to assess additional findings. Of 2267 potential studies, 165 met the inclusion criteria. The healthy volunteer meta-analysis included 339 subjects and found a mean OEF value of 38.87 (37.38, 40.36), with a prediction interval of 32.40-45.34. There were no statistical differences in OEF values derived from PET versus MRI. We provided a GRADE A certainty rating for the use of OEF metrics to predict stroke occurrence in patients with symptomatic carotid or cerebral vessel disease. We provided a GRADE B certainty rating for monitoring treatment response in Moyamoya disease. Use of OEF metrics in diagnosing and/or monitoring other conditions had a GRADE C certainty rating or less. OEF might have a role in diagnosing and monitoring patients with symptomatic carotid or cerebral vessel disease and Moyamoya disease. While we found insufficient evidence to support measuring OEF metrics in other patient populations, in many cases, further studies are warranted.

The changes of oxygen extraction fraction in different types of lesions in relapsing-remitting multiple sclerosis: A cross-sectional and longitudinal study.

OBJECTIVES: To explore the oxygen metabolism level of different types of lesions in relapsing-remitting multiple sclerosis (RRMS) patients by oxygen extraction fraction (OEF) both cross-sectionally and longitudinally. METHODS: Forty-six RRMS patients and forty-one healthy controls (HC) went MRI examination. The quantitative susceptibility mapping (QSM) and OEF map were reconstructed from a 3D multi-echo gradient echo sequence. MS lesions in white matter were classified as contrast-enhancing lesions (CELs) on post-gadolinium T1-weighted sequence, paramagnetic rim lesions (PRLs), hyperintense lesions and non-hyperintense lesions on QSM, respectively. The susceptibility and OEF of different types of lesions were compared. The susceptibility and OEF values were measured and compared among different types of lesions. Among these RRMS patients, seventeen had follow-up MRI and 232 lesions, and baseline to follow-up longitudinal changes in susceptibility and OEF were measured. RESULTS: PRLs had higher susceptibility and lower OEF than CELs, hyperintense lesions, and non-hyperintense lesions. The hyperintense lesions had higher susceptibility and lower OEF than non-hyperintense lesions. In longitudinal changes, PRLs had susceptibility increased (P < 0.001) and OEF decreased (P < 0.001). The hyperintense lesions showed significant decreases in susceptibility (P = 0.020), and non-hyperintense lesions showed significant increases in OEF during follow-up (P = 0.005). Notably, hyperintense lesions may convert to PRLs or non-hyperintense lesions as time progresses, accompanied by changes of OEF and susceptibility in the lesions. CONCLUSION: This study revealed tissue damage and oxygen metabolism level in different types of MS lesions. The OEF may contribute to further understanding the evolution of MS lesions.

Peripheral limitations for performance: Muscle capillarization.

Sufficient delivery of oxygen and metabolic substrates, together with removal of waste products, are key elements of muscle performance. Capillaries are the primary site for this exchange in skeletal muscle and the degree of muscle capillarization affects diffusion conditions by influencing mean transit time, capillary surface area and diffusion distance. Muscle capillarization may thus represent a limiting factor for performance. Exercise training increases the number of capillaries per muscle fiber by about 10%-20% within a few weeks in untrained subjects, whereas capillary growth progresses more slowly in well-trained endurance athletes. Studies show that capillaries are tortuous, situated along and across the length of the fibers with an arrangement related to muscle fascicles. Although direct data is lacking, it is possible that years of training not only enhances capillary density but also optimizes the positioning of capillaries, to further improve the diffusion conditions. Muscle capillarization has been shown to increase oxygen extraction during exercise in humans, but direct evidence for a causal link between increased muscle capillarization and performance is scarce. This review covers current knowledge on the implications of muscle capillarization for oxygen and glucose uptake as well as performance. A brief overview of the process of capillary growth and of physical factors, inherent to exercise, which promote angiogenesis, provides the foundation for a discussion on how different training modalities may influence muscle capillary growth. Finally, we identify three areas for future research on the role of capillarization for exercise performance.

Subtetanic neuromuscular electrical stimulation can maintain Wingate test performance but augment blood lactate accumulation.

PURPOSE: Concentration- and time-dependent effect of lactate on physiological adaptation (i.e., glycolytic adaptation and mitochondrial biogenesis) have been reported. Subtetanic neuromuscular electrical stimulation (NMES) with voluntary exercise (VOLES) can increase blood lactate accumulation. However, whether this is also true that VOLES can enhance the blood lactate accumulation during sprint exercise is unknown. Thus, we investigated whether VOLES before the Wingate test can enhance blood lactate accumulation without compromising Wingate exercise performance. METHODS: Fifteen healthy young males (mean [SD], age: 23 [4] years, body mass index: 22.0 [2.1] kg/m2) volunteered. After resting measurement, participants performed a 3-min intervention: VOLES (NMES with free-weight cycling) or voluntary cycling alone, which matched exercise intensity with VOLES (VOL, 43.6 [8.0] watt). Then, they performed the Wingate test with 30 min free-weight cycling recovery. The blood lactate concentration ([La]b) was assessed at the end of resting and intervention, and recovery at 1, 3, 5, 10, 20, and 30 min. RESULTS: [La]b during intervention was higher with VOLES than VOL (P = 0.011). The increase in [La]b after the Wingate test was maintained for longer with VOLES than VOL at 10- and 20-min recovery (P = 0.014 and 0.023, respectively). Based on the Wingate test, peak power, mean power, and the rate of decline were not significantly different between VOLES and VOL (P = 0.184, 0.201, and 0.483, respectively). CONCLUSION: The combination of subtetanic NMES with voluntary exercise before the Wingate test has the potential to enhance blood lactate accumulation. Importantly, this combined approach does not compromise Wingate exercise performance compared to voluntary exercise alone.

Muscle deoxygenation during ramp incremental cycle exercise in older adults with type 2 diabetes.

PURPOSE: To explore profiles of fractional O2 extraction (using near-infrared spectroscopy) during ramp incremental cycling in older individuals with type 2 diabetes (T2D). METHODS: Twelve individuals with T2D (mean ± SD, age: 63 ± 3 years) and 12 healthy controls (mean age: 65 ± 3 years) completed a ramp cycling exercise. Rates of muscle deoxygenation (i.e., deoxygenated haemoglobin and myoglobin, Δ[HHb + Mb]) profiles of the vastus lateralis muscle were normalised to 100% of the response, plotted against absolute (W) and relative (%peak) power output (PO) and fitted with a double linear regression model. RESULTS: Peak oxygen uptake (V̇O2peak) was significantly (P < 0.01) reduced in T2D (23.0 ± 4.2 ml.kg-1.min-1) compared with controls (28.3 ± 5.3 ml.kg-1.min-1). The slope of the first linear segment of the model was greater (median (interquartile range)) in T2D (1.06 (1.50)) than controls (0.79 (1.06)) when Δ%[HHb + Mb] was plotted as a function of PO. In addition, the onset of the second linear segment of the Δ%[HHb + Mb]/PO model occurred at a lower exercise intensity in T2D (101 ± 35 W) than controls (140 ± 34 W) and it displayed a near-plateau response in both groups. When the relationship of the Δ%[HHb + Mb] profile was expressed as a function of %PO no differences were observed in any parameters of the double linear model. CONCLUSIONS: These findings suggest that older individuals with uncomplicated T2D demonstrate greater fractional oxygen extraction for a given absolute PO compared with older controls. Thus, the reductions in V̇O2peak in older people with T2D are likely influenced by impairments in microvascular O2 delivery.

Standard versus High Cardiopulmonary Bypass Flow Rate: A Randomized Controlled Subtrial Comparing Brain Injury Biomarker Release.

OBJECTIVES: To compare brain injury biomarker release levels between two different cardiopulmonary bypass (CPB) flow rates in elective cardiac surgery and to explore differences in postoperative delirium between groups and associations between age, sex, CPB time, oxygen levels, and near-infrared spectroscopy, and biomarker levels. DESIGN: A randomized controlled substudy trial SETTING: Sahlgrenska University Hospital, Sweden PARTICIPANTS: Forty patients undergoing elective cardiac surgery with CPB INTERVENTION: Patients were assigned at random to either a standard (2.4 L/min/m2) or a high (2.9 L/min/m2) CPB flow rate. MEASUREMENTS AND MAIN RESULTS: Glial fibrillary acidic protein, neurofilament light chain, total-tau, and phosphorylated-tau217 were sampled in plasma before anesthesia induction, after 60 minutes on CPB, and at 30 minutes, 24 hours, and 72 hours post-CPB. Mixed models for repeated measures were used to analyze differences in biomarker levels between groups and to assess relationships, which showed no differences between the 2 flow rate groups. There also was no difference in the occurrence of delirium between the 2 groups. Associations were found between age and increased neurofilament light chain levels. Female sex, oxygen delivery >330 mL/min/m2, and near-infrared spectroscopy level >60% were associated with lower biomarker levels. CONCLUSIONS: An increased flow rate did not have any significant effects on biomarker levels compared to a standard flow rate. Several associations were identified between treatment characteristics and biomarker levels. No difference in delirium was seen.

Changes in regional tissue oxygen saturation values during the first week of life in stable preterm infants.

OBJECTIVES: Near infrared spectroscopy (NIRS) is a non-invasive method for monitoring regional tissue oxygen saturation (rSO2). The purpose of this study is to investigate the changes that occur in cerebral, splanchnic, and renal rSO2 and fractional tissue oxygen extraction (FTOE) in stable preterm infants in the first week of life. METHODS: Prospective observational study of infants born 30-34 weeks gestation at NYU Langone Health between November 2017 and November 2018. Cerebral, renal, and splanchnic rSO2 were monitored from 12 to 72 h of life, and at seven days. Subjects were divided into gestational age (GA) cohorts. Average rSO2, splanchnic cerebral oxygen ratio (SCOR), FTOE, and regional intra-subject variability was calculated at each location at five different time intervals: 0-12 h, 12-24 h, 24-48 h, 48-72 h, and one week of life. RESULTS: Twenty subjects were enrolled. The average cerebral rSO2 ranged from 76.8 to 92.8 %, renal rSO2 from 65.1 to 91.1 %, and splanchnic rSO2 from 36.1 to 76.3 %. The SCOR ranged from 0.45 to 0.94. The strongest correlation between the GA cohorts was in the cerebral region (R2=0.94) and weakest correlation was in the splanchnic region (R2=0.81). The FTOE increased in all three locations over time. Intra-subject variability was lowest in the cerebral region (1.3 % (±1.9)). CONCLUSIONS: The cerebral region showed the strongest correlation between GA cohorts and lowest intra-subject variability, making it the most suitable for clinical use when monitoring for tissue hypoxia. Further studies are needed to further examine rSO2 in preterm infants.

Factors associated with renal oxygen extraction in mechanically ventilated children after the Norwood operation: insights from high fidelity haemodynamic data.

BACKGROUND: Maintaining the adequacy of systemic oxygen delivery is of utmost importance, particularly in critically ill children. Renal oxygen extraction can be utilised as metric of the balance between systemic oxygen delivery and oxygen consumption. The primary aim of this study was to determine what clinical factors are associated with renal oxygen extraction in children after Norwood procedure. METHODS: Mechanically ventilated children who underwent Norwood procedure from 1 September, 2022 to 1 March, 2023 were identified as these patients had data collected and stored with high fidelity by the T3 software. Data regarding haemodynamic values, fluid balance, and airway pressure were collected and analysed using Bayesian regression to determine the association of the individual metrics with renal oxygen extraction. RESULTS: A total of 27,270 datapoints were included in the final analyses. The resulting top two models explained had nearly 80% probability of being true and explained over 90% of the variance in renal oxygen extraction. The coefficients for each variable retained in the best were -1.70 for milrinone, -19.05 for epinephrine, 0.129 for mean airway pressure, -0.063 for mean arterial pressure, 0.111 for central venous pressure, 0.093 for arterial saturation, 0.006 for heart rate, -0.025 for respiratory rate, 0.366 for systemic vascular resistance, and -0.032 for systemic blood flow. CONCLUSION: Increased milrinone, epinephrine, mean arterial pressure, and systemic blood flow were associated with decreased (improved) renal oxygen extraction, while increased mean airway pressure, central venous pressure, arterial saturation, and systemic vascular resistance were associated with increased (worsened) renal oxygen extraction.

MRI assessment of cerebral oxygen extraction fraction in the medial temporal lobe.

The medial temporal lobe (MTL) is a key area implicated in many brain diseases, such as Alzheimer's disease. As a functional biomarker, the oxygen extraction fraction (OEF) of MTL may be more sensitive than structural atrophy of MTL, especially at the early stages of diseases. However, there is a lack of non-invasive techniques to measure MTL-OEF in humans. The goal of this work is to develop an MRI technique to assess MTL-OEF in a clinically practical time without using contrast agents. The proposed method measures venous oxygenation (Yv) in the basal veins of Rosenthal (BVs), which are the major draining veins of the MTL. MTL-OEF can then be estimated as the arterio-venous difference in oxygenation. We developed an MRI sequence, dubbed arterial-suppressed accelerated T2-relaxation-under-phase-contrast (AS-aTRUPC), to quantify the blood T2 of the BVs, which was then converted to Yv through a well-established calibration model. MTL-OEF was calculated as (Ya-Yv)/Ya × 100%, where Ya was the arterial oxygenation. The feasibility of AS-aTRUPC to quantify MTL-OEF was evaluated in 16 healthy adults. The sensitivity of AS-aTRUPC in detecting OEF changes was assessed by a caffeine ingestion (200 mg) challenge. For comparison, T2-relaxation-under-spin-tagging (TRUST) MRI, which is a widely used global OEF technique, was also acquired. The dependence of MTL-OEF on age was examined by including another seven healthy elderly subjects. The results showed that in healthy adults, MTL-OEF of the left and right hemispheres were correlated (P=0.005). MTL-OEF was measured to be 23.9±3.6% (mean±standard deviation) and was significantly lower (P<0.0001) than the OEF of 33.3±2.9% measured in superior sagittal sinus (SSS). After caffeine ingestion, there was an absolute percentage increase of 9.1±4.0% in MTL-OEF. Additionally, OEF in SSS measured with AS-aTRUPC showed a strong correlation with TRUST OEF (intra-class correlation coefficient=0.94 with 95% confidence interval [0.91, 0.96]), with no significant bias (P=0.12). MTL-OEF was found to increase with age (MTL-OEF=20.997+0.100 × age; P=0.02). In conclusion, AS-aTRUPC MRI provides non-invasive assessments of MTL-OEF and may facilitate future clinical applications of MTL-OEF as a disease biomarker.

Cerebral oxygen metabolism from MRI susceptibility.

This article provides an overview of MRI methods exploiting magnetic susceptibility properties of blood to assess cerebral oxygen metabolism, including the tissue oxygen extraction fraction (OEF) and the cerebral metabolic rate of oxygen (CMRO2). The first section is devoted to describing blood magnetic susceptibility and its effect on the MRI signal. Blood circulating in the vasculature can have diamagnetic (oxyhemoglobin) or paramagnetic properties (deoxyhemoglobin). The overall balance between oxygenated and deoxygenated hemoglobin determines the induced magnetic field which, in turn, modulates the transverse relaxation decay of the MRI signal via additional phase accumulation. The following sections of this review then illustrate the principles underpinning susceptibility-based techniques for quantifying OEF and CMRO2. Here, it is detailed whether these techniques provide global (OxFlow) or local (Quantitative Susceptibility Mapping - QSM, calibrated BOLD - cBOLD, quantitative BOLD - qBOLD, QSM+qBOLD) measurements of OEF or CMRO2, and what signal components (magnitude or phase) and tissue pools they consider (intravascular or extravascular). Validations studies and potential limitations of each method are also described. The latter include (but are not limited to) challenges in the experimental setup, the accuracy of signal modeling, and assumptions on the measured signal. The last section outlines the clinical uses of these techniques in healthy aging and neurodegenerative diseases and contextualizes these reports relative to results from gold-standard PET.

Evaluation of whole-brain oxygen metabolism in Alzheimer's disease using QSM and quantitative BOLD.

OBJECTIVE: The objective of this study was to evaluate the whole-brain pattern of oxygen extraction fraction (OEF), cerebral blood flow (CBF), and cerebral metabolic rate of oxygen consumption (CMRO2) perturbation in Alzheimer's disease (AD) and investigate the relationship between regional cerebral oxygen metabolism and global cognition. METHODS: Twenty-six AD patients and 25 age-matched healthy controls (HC) were prospectively recruited in this study. Mini-Mental State Examination (MMSE) was used to evaluate cognitive status. We applied the QQ-CCTV algorithm which combines quantitative susceptibility mapping and quantitative blood oxygen level-dependent models (QQ) for OEF calculation. CBF map was computed from arterial spin labeling and CMRO2 was generated based on Fick's principle. Whole-brain and regional OEF, CBF, and CMRO2 analyses were performed. The associations between these measures in substructures of deep brain gray matter and MMSE scores were assessed. RESULTS: Whole brain voxel-wise analysis showed that CBF and CMRO2 values significantly decreased in AD predominantly in the bilateral angular gyrus, precuneus gyrus and parieto-temporal regions. Regional analysis showed that CBF value decreased in the bilateral caudal hippocampus and left rostral hippocampus and CMRO2 value decreased in left caudal and rostral hippocampus in AD patients. Considering all subjects in the AD and HC groups combined, the mean CBF and CMRO2 values in the bilateral hippocampus positively correlated with the MMSE score. CONCLUSION: CMRO2 mapping with the QQ-CCTV method - which is readily available in MR systems for clinical practice - can be a potential biomarker for AD. In addition, CMRO2 in the hippocampus may be a useful tool for monitoring cognitive impairment.

Vascular space occupancy asymmetric spin echo (VASO-ASE) for non-invasive quantification of cerebral oxygen extraction fraction.

PURPOSE: Asymmetric spin echo (ASE) MRI is a method for measuring regional oxygen extraction fraction (OEF); however, extravascular tissue models have been shown to under-estimate OEF. The hypothesis investigated here is that the addition of a vascular-space-occupancy (VASO) pre-pulse will more fully suppress blood water signal and provide global OEF values more consistent with physiological expectation and 15 O positron emission tomography (PET)-validated T2 -relaxation-under-spin-tagging (TRUST) OEF measures. METHODS: Healthy adults (n = 14; age = 27.7 ± 5.2 y; sex = 7/7 male/female) were scanned at 3.0T. Multi-echo ASE without inter-readout refocusing (ASERF- ), multi-echo ASE with inter-readout refocusing (ASERF+ ), and single-echo VASO-ASE were acquired twice each with common spatial resolution = 3.44 × 3.44 × 3.0 mm and τ = 0-20 ms (interval = 0.5 ms). TRUST was acquired twice sequentially for independent global OEF assessment (τCPMG  = 10 ms; effective TEs = 0, 40, 80, and 160 ms; spatial resolution = 3.4 × 3.4 × 5 mm). OEF intraclass-correlation-coefficients (ICC), summary statistics, and group-wise differences were assessed (Wilcoxon rank-sum; significance: two-sided p < 0.05). RESULTS: ASERF+ (OEF = 36.8 ± 1.9%) and VASO-ASE (OEF = 34.4 ± 2.3%) produced OEF values similar to TRUST (OEF = 36.5 ± 4.6%, human calibration model; OEF = 32.7 ± 4.9%, bovine calibration model); however, ASERF- yielded lower OEF (OEF = 26.1 ± 1.0%; p < 0.01) relative to TRUST. VASO-ASE (ICC = 0.61) yielded lower ICC compared to other ASE variants (ICC >0.89). CONCLUSION: VASO-ASE and TRUST provide similar OEF values; however, VASO-ASE spatial coverage and repeatability improvements are required.

Skeletal muscle abnormalities in heart failure with preserved ejection fraction.

Almost half of all heart failure (HF) disease burden is due to HF with preserved ejection fraction (HFpEF). The primary symptom in patients with HFpEF, even when well compensated, is severe exercise intolerance and is associated with their reduced quality of life. Recently, studies showed that HFpEF patients have multiple skeletal muscle (SM) abnormalities, and these are associated with decreased exercise intolerance. The SM abnormalities are likely intrinsic to the HFpEF syndrome, not a secondary consequence of an epiphenomenon. These abnormalities are decreased muscle mass, reduced type I (oxidative) muscle fibers, and reduced type I-to-type II fiber ratio as well as a reduced capillary-to-fiber ratio, abnormal fat infiltration into the thigh SM, increased levels of atrophy genes and proteins, reduction in mitochondrial content, and rapid depletion of high-energy phosphate during exercise with markedly delayed repletion of high-energy phosphate during recovery in mitochondria. In addition, patients with HFpEF have impaired nitric oxide bioavailability, particularly in the microvasculature. These SM abnormalities may be responsible for impaired diffusive oxygen transport and/or impaired SM oxygen extraction. To date, exercise training (ET) and caloric restriction are some of the interventions shown to improve outcomes in HFpEF patients. Improvements in exercise tolerance following aerobic ET are largely mediated through peripheral SM adaptations with minimal change in central hemodynamics and highlight the importance of targeting SM to improve exercise intolerance in HFpEF. Focusing on the abnormalities mentioned above may improve the clinical condition of patients with HFpEF.

Red cell exchange transfusions increase cerebral capillary transit times and may alter oxygen extraction in sickle cell disease.

Persons with sickle cell disease (SCD) suffer from chronic hemolytic anemia, reduced blood oxygen content, and lifelong risk of silent and overt stroke. Major conventional stroke risk factors are absent in most individuals with SCD, yet nearly 50% have evidence of brain infarcts by the age of 30 years, indicating alternative etiologies for ischemia. We investigated whether radiological evidence of accelerated blood water transit through capillaries, visible on arterial spin labeling (ASL) magnetic resonance imaging, reduces following transfusion-induced increases in hemoglobin and relates to oxygen extraction fraction (OEF). Neurological evaluation along with anatomical and hemodynamic imaging with cerebral blood flow (CBF)-weighted pseudocontinuous ASL and OEF imaging with T2 -relaxation-under-spin-tagging were applied in sequence before and after blood transfusion therapy (n = 32) and in a comparator cohort of nontransfused SCD participants on hydroxyurea therapy scanned at two time points to assess stability without interim intervention (n = 13). OEF was calculated separately using models derived from human hemoglobin-F, hemoglobin-A, and hemoglobin-S. Gray matter CBF and dural sinus signal, indicative of rapid blood transit, were evaluated at each time point and compared with OEF using paired statistical tests (significance: two-sided p < 0.05). No significant change in sinus signal was observed in nontransfused participants (p = 0.650), but a reduction was observed in transfused participants (p = 0.034), consistent with slower red cell transit following transfusion. The dural sinus signal intensity was inversely associated with OEF pretransfusion (p = 0.011), but not posttransfusion. Study findings suggest that transfusion-induced increases in total hemoglobin may lengthen blood transit times through cerebral capillaries and alter cerebral OEF in SCD.

Venous Blood Oxygenation Measurements Using TRUST and T2-TRIR MRI During Hypoxic and Hypercapnic Gas Challenges.

BACKGROUND: Oxygen extraction fraction (OEF) and cerebral metabolic rate of oxygen (CMRO2 ) may serve as biomarkers in several diseases. OEF and CMRO2 can be estimated from venous blood oxygenation (Yv ) levels, which in turn can be calculated from venous blood T2 values (T2b ). T2b can be measured using different MRI sequences, including T2-relaxation-under-spin-tagging (TRUST) and T2-prepared-blood-relaxation-imaging-with-inversion-recovery (T2-TRIR). The latter measures both T2b and T1 (T1b ) but was found previously to overestimate T2b compared to TRUST. It remained unclear, however, if this bias is constant across higher and lower oxygen saturations. PURPOSE: To compare TRUST and T2-TRIR across a range of O2 saturations using hypoxic and hypercapnic gas challenges. STUDY TYPE: Prospective. POPULATION: Twelve healthy volunteers (four female, age 36 ± 10 years). FIELD STRENGTH/SEQUENCE: A 3T; turbo-field echo-planar-imaging (TFEPI), echo-planar-imaging (EPI), and fast-field-echo (FFE). ASSESSMENT: TRUST- and T2-TRIR-derived T2b , Yv , OEF, and CMRO2 were compared across different respiratory challenges. T1b from T2-TRIR was used to estimate Hct (HctTRIR ) and compared with venipuncture (HctVP ). STATISTICAL TESTS: Shapiro-Wilk, one-sample and paired-sample t-test, repeated measures ANOVA, Friedman test, Bland-Altman, and correlation analysis. Bonferroni multiple-comparison correction was performed. Significance level was 0.05. RESULTS: A significant bias was observed between TRUST- and T2-TRIR-derived T2b , Yv , and OEF values (-13 ± 11 msec, -5.3% ± 3.5% and 5.9 ± 4.1%, respectively). For Yv and OEF, this bias was constant across the range of measured values. T1b was significantly lower during severe hypoxia and hypercapnia compared to baseline (1712 ± 86 msec and 1634 ± 79 msec compared to 1757 ± 90 msec). While no significant bias was found between HctVP and HctTRIR (0.02% ± 0.06%, P = 0.20), the correlation between these Hct values was significant but weak (r = 0.19). DATA CONCLUSION: Given the constant bias, TRUST- and T2-TRIR-derived venous T2b values can be used interchangeably to estimate Yv , OEF, and CMRO2 across a broad range of oxygen saturations. Hct from T2-TRIR-derived T1-values only weakly correlated with Hct from venipuncture. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 2.

Energy metabolism and muscle activation heterogeneity explain V ̇ O 2 ${\dot{V}}_{{{\rm{O}}}_{\rm{2}}}$ slow component and muscle fatigue of cycling at different intensities.

NEW FINDINGS: What is the central question of this study? What are the physiological mechanisms underlying muscle fatigue and the increase in the O2 cost per unit of work during high-intensity exercise? What is the main finding and its importance? Muscle fatigue happens before, and does not explain, the V ̇ O 2 ${\dot{V}}_{{{\rm{O}}}_{\rm{2}}}$ slow component ( V ̇ O 2 sc ${\dot{V}}_{{{\rm{O}}}_{\rm{2}}{\rm{sc}}}$ ), but they share the same origin. Muscle activation heterogeneity is associated with muscle fatigue and V ̇ O 2 sc ${\dot{V}}_{{{\rm{O}}}_{\rm{2}}{\rm{sc}}}$ . Knowing this may improve training prescriptions for healthy people leading to improved public health outcomes. ABSTRACT: This study aimed to explain the V ̇ O 2 ${\dot{V}}_{{{\rm{O}}}_{\rm{2}}}$ slow component ( V ̇ O 2 sc ${\dot{V}}_{{{\rm{O}}}_{\rm{2}}{\rm{sc}}}$ ) and muscle fatigue during cycling at different intensities. The muscle fatigue of 16 participants was determined through maximal isokinetic effort lasting 3 s during constant work rate bouts of moderate (MOD), heavy (HVY) and very heavy intensity (VHI) exercise. Breath-by-breath V ̇ O 2 ${\dot{V}}_{{{\rm{O}}}_{\rm{2}}}$ , near-infrared spectroscopy signals and EMG activity were analysed (thigh muscles). V ̇ O 2 sc ${\dot{V}}_{{{\rm{O}}}_{\rm{2}}{\rm{sc}}}$ was higher during VHI exercise (∼70% vs. ∼28% of V ̇ O 2 ${\dot{V}}_{{{\rm{O}}}_{\rm{2}}}$ reserve in HVY). The deoxygenated haemoglobin final value during VHI exercise was higher than during HVY and MOD exercise (∼90% of HHb physiological normalization, vs. ∼82% HVY and ∼45% MOD). The muscle fatigue was greater after VHI exercise (∼22% vs. HVY ∼5%). There was no muscle fatigue after MOD exercise. The greatest magnitude of muscle fatigue occurred within 2 min (VHI ∼17%; HVY ∼9%), after which it stabilized. No significant relationship between V ̇ O 2 sc ${\dot{V}}_{{{\rm{O}}}_{\rm{2}}{\rm{sc}}}$ and muscle force production was observed. The τ of muscle V ̇ O 2 ${\dot{V}}_{{{\rm{O}}}_{\rm{2}}}$ was significantly related (R2  = 0.47) with torque decrease for VHI. Type I and II muscle fibre recruitment mainly in the rectus femoris moderately explained the muscle fatigue (R2  = 0.30 and 0.31, respectively) and the V ̇ O 2 sc ${\dot{V}}_{{{\rm{O}}}_{\rm{2}}{\rm{sc}}}$ (R2  = 0.39 and 0.27, respectively). The V ̇ O 2 sc ${\dot{V}}_{{{\rm{O}}}_{\rm{2}}{\rm{sc}}}$ is also partially explained by blood lactate accumulation (R2  = 0.42). In conclusion muscle fatigue and O2 cost seem to share the same physiological cause linked with a decrease in the muscle V ̇ O 2 ${\dot{V}}_{{{\rm{O}}}_{\rm{2}}}$ and a change in lactate accumulation. Muscle fatigue and V ̇ O 2 sc ${\dot{V}}_{{{\rm{O}}}_{\rm{2}}{\rm{sc}}}$ are associated with muscle activation heterogeneity and metabolism of different muscles activated during cycling.