Inter-rater reliability of functional MRI data quality control assessments: A standardised protocol and practical guide using pyfMRIqc.

Quality control is a critical step in the processing and analysis of functional magnetic resonance imaging data. Its purpose is to remove problematic data that could otherwise lead to downstream errors in the analysis and reporting of results. The manual inspection of data can be a laborious and error-prone process that is susceptible to human error. The development of automated tools aims to mitigate these issues. One such tool is pyfMRIqc, which we previously developed as a user-friendly method for assessing data quality. Yet, these methods still generate output that requires subjective interpretations about whether the quality of a given dataset meets an acceptable standard for further analysis. Here we present a quality control protocol using pyfMRIqc and assess the inter-rater reliability of four independent raters using this protocol for data from the fMRI Open QC project (https://osf.io/qaesm/). Data were classified by raters as either "include," "uncertain," or "exclude." There was moderate to substantial agreement between raters for "include" and "exclude," but little to no agreement for "uncertain." In most cases only a single rater used the "uncertain" classification for a given participant's data, with the remaining raters showing agreement for "include"/"exclude" decisions in all but one case. We suggest several approaches to increase rater agreement and reduce disagreement for "uncertain" cases, aiding classification consistency.

The influence of short-term high-altitude acclimatization on cerebral and leg tissue oxygenation post-orthostasis.

PURPOSE: Orthostasis at sea level decreases brain tissue oxygenation and increases risk of syncope. High altitude reduces brain and peripheral muscle tissue oxygenation. This study determined the effect of short-term altitude acclimatization on cerebral and peripheral leg tissue oxygenation index (TOI) post-orthostasis. METHOD: Seven lowlanders completed a supine-to-stand maneuver at sea level (450 m) and for 3 consecutive days at high altitude (3776 m). Cardiorespiratory measurements and near-infrared spectroscopy-derived oxygenation of the frontal lobe (cerebral TOI) and vastus lateralis (leg TOI) were measured at supine and 5-min post-orthostasis. RESULTS: After orthostasis at sea level, cerebral TOI decreased [mean Δ% (95% confidential interval): - 4.5%, (- 7.5, - 1.5), P < 0.001], whilst leg TOI was unchanged [- 4.6%, (- 10.9, 1.7), P = 0.42]. High altitude had no effect on cerebral TOI following orthostasis [days 1-3: - 2.3%, (- 5.3, 0.7); - 2.4%, (- 5.4, 0.6); - 2.1%, (- 5.1, 0.9), respectively, all P > 0.05], whereas leg TOI decreased [days 1-3: - 12.0%, (- 18.3, - 5.7); - 12.1%, (- 18.4, - 5.8); - 10.2%, (- 16.5, - 3.9), respectively, all P < 0.001]. This response did not differ with days spent at high altitude, despite evidence of cardiorespiratory acclimatization [increased peripheral oxygen saturation (supine: P = 0.01; stand: P = 0.02) and decreased end-tidal carbon dioxide (supine: P = 0.003; stand: P = 0.01)]. CONCLUSION: Cerebral oxygenation is preferentially maintained over leg oxygenation post-orthostasis at high altitude, suggesting different vascular regulation between cerebral and peripheral circulations. Short-term acclimatization to high altitude did not alter cerebral and leg oxygenation responses to orthostasis.

The deleterious effects of acute hypoxia on microvascular and large vessel endothelial function.

NEW FINDINGS: What is the central question of this study? The aim was primarily to determine the effect of hypoxia on microvascular function and secondarily whether superior cardiorespiratory fitness is protective against hypoxia-induced impairment in vascular function. What is the main finding and its importance? Hypoxia reduced endothelium-dependent but not endothelium-independent microvascular function. The extent of impairment was twofold higher in the microcirculation compared with the large blood vessels. This study suggests that individuals with superior cardiorespiratory fitness might preserve microvascular function in hypoxia. These findings highlight the sensitivity of the microvascular circulation to hypoxia. ABSTRACT: Hypoxia is associated with diminished bioavailability of the endothelium-derived vasodilator, nitric oxide (NO). Diminished NO bioavailability can have deleterious effects on endothelial function. The endothelium is a heterogeneous tissue; therefore, a comprehensive assessment of endothelial function is crucial to understand the significance of hypoxia-induced endothelial dysfunction. We hypothesized that acute hypoxia would have a deleterious effect on microvascular and large vessel endothelial function. Twenty-nine healthy adults [24 (SD = 4 ) years of age] completed normoxic and hypoxic [inspired O2  fraction = 0.209] trials in this double-blinded, counterbalanced crossover study. After 30 min, we assessed the laser Doppler imaging-determined perfusion response to iontophoresis of ACh as a measure of endothelium-dependent microvascular function and iontophoresis of sodium nitroprusside as a measure of endothelium-independent microvascular function. After 60 min, we assessed brachial flow-mediated dilatation as a measure of large vessel endothelial function. Thirty minutes of hypoxia reduced endothelium-dependent microvascular function determined by the perfusion response to ACh (median difference (x̃∆) = -109% {interquartile range: 542.7}, P < 0.05), but not endothelium-independent microvascular function determined by the perfusion response to sodium nitroprusside (x̃∆ = 69% {interquartile range: 453.7}, P = 0.6). In addition, 60 min of hypoxia reduced allometrically scaled flow-mediated dilatation compared with normoxia ( x¯Δ=-1.19 [95% CI = -1.80, -0.58 (Confidence Intervals)]%, P < 0.001). The decrease in microvascular endothelial function was associated with cardiorespiratory fitness (r  = 0.45, P = 0.02). In conclusion, acute exposure to normobaric hypoxia significantly reduced endothelium-dependent vasodilatory capacity in small and large vessels. Collectively, these findings highlight the sensitivity of the microvascular circulation to hypoxic insult, particularly in those with poor cardiorespiratory fitness.

Bilateral regional extracranial blood flow regulation to hypoxia and unilateral duplex ultrasound measurement error.

NEW FINDINGS: What is the central question of this study? Is blood flow regulation to hypoxia different between the internal carotid arteries (ICAs) and vertebral arteries (VAs), and what is the measurement error in unilateral extracranial artery assessments compared to bilateral? What is the main finding and its importance? ICA and VA blood flow regulation to hypoxia is comparable when factoring for vessel type and vessel side. Compared to bilateral assessment, vessels assessed unilaterally had individual measurement errors of up to 37%. Assessing the vessel with the larger resting blood flow, not the left or right vessel, reduces unilateral measurement error. ABSTRACT: Whether blood flow regulation to hypoxia is similar between left and right internal carotid arteries (ICAs) and vertebral arteries (VAs) is unclear. Extracranial blood flow is regularly calculated by doubling a unilateral assessment; however, lateral artery differences may lead to measurement error. This study aimed to determine extracranial blood flow regulation to hypoxia when factoring for vessel type (ICAs or VAs) and vessel side (left or right) effects, and to investigate unilateral assessment measurement error compared to bilateral assessment. In a repeated-measures crossover design, extracranial arteries of 44 participants were assessed bilaterally by duplex ultrasound during 90 min of normoxic and poikilocapnic hypoxic (12.0% fraction of inspired oxygen) conditions. Linear mixed model analyses revealed no Condition × Vessel Type × Vessel Side interaction for blood flow, vessel diameter and flow velocity (all P > 0.05) indicating left and right ICA and VA blood flow regulation to hypoxia was similar. Bilateral hypoxic reactivity was comparable (ICAs, 1.4 (1.0) vs. VAs, 1.7 (1.1) Δ%·Δ SpO2-1 ; P = 0.12). Compared to bilateral assessment, unilateral mean measurement error of the relative blood flow response to hypoxia was up to 5%, but individual errors reached 37% and were greatest in ICAs and VAs with the smaller resting blood flow due to a ratio-scaling problem. In conclusion, left and right ICA and VA regulation to hypoxia is comparable when factoring for vessel type and vessel side. Assessing the ICA and VA vessels with the larger resting blood flow, not the left or right vessel, reduces unilateral measurement error.

Dietary nitrate supplementation increases acute mountain sickness severity and sense of effort during hypoxic exercise.

Dietary nitrate supplementation enhances sea level performance and may ameliorate hypoxemia at high altitude. However, nitrate may exacerbate acute mountain sickness (AMS), specifically headache. This study investigated the effect of nitrate supplementation on AMS symptoms and exercise responses with 6-h hypoxia. Twenty recreationally active men [age, 22 ± 4 yr, maximal oxygen consumption (V̇o2max), 51 ± 6 ml·min-1·kg-1, means ± SD] completed this randomized double-blinded placebo-controlled crossover study. Twelve participants were classified as AMS- on the basis of Environmental Symptoms Questionnaire [Acute Cerebral Mountain Sickness score (AMS-C)] <0.7 in both trials, and five participants were classified as AMS+ on the basis of AMS-C ≥0.7 on placebo. Five days of nitrate supplementation (70-ml beetroot juice containing ~6.4 mmol nitrate daily) increased plasma NO metabolites by 182 µM compared with placebo but did not reduce AMS or improve exercise performance. After 4-h hypoxia [inspired O2 fraction ([Formula: see text]) = 0.124], nitrate increased AMS-C and headache severity (visual analog scale; whole sample ∆10 [1, 20] mm, mean difference [95% confidence interval]; P = 0.03) compared with placebo. In addition, after 5-h hypoxia, nitrate increased sense of effort during submaximal exercise (∆7 [-1, 14]; P = 0.07). In AMS-, nitrate did not alter headache or sense of effort. In contrast, in AMS+, nitrate increased headache severity (∆26 [-3, 56] mm; P = 0.07), sense of effort (∆14 [1, 28]; P = 0.04), oxygen consumption, ventilation, and mean arterial pressure during submaximal exercise. On the next day, in a separate acute hypoxic exercise test ([Formula: see text] = 0.141), nitrate did not improve time to exhaustion at 80% hypoxic V̇o2max In conclusion, dietary nitrate increases AMS and sense of effort during exercise, particularly in those who experience AMS. Dietary nitrate is therefore not recommended as an AMS prophylactic or ergogenic aid in nonacclimatized individuals at altitude.NEW & NOTEWORTHY This is the first study to identify that the popular dietary nitrate supplement (beetroot) does not reduce acute mountain sickness (AMS) or improve exercise performance during 6-h hypoxia. The consumption of nitrate in those susceptible to AMS exacerbates AMS symptoms (headache) and sense of effort and raises oxygen cost, ventilation, and blood pressure during walking exercise in 6-h hypoxia. These data question the suitability of nitrate supplementation during altitude travel in nonacclimatized people.

MEDEX2015: Greater Sea-Level Fitness Is Associated with Lower Sense of Effort During Himalayan Trekking Without Worse Acute Mountain Sickness.

Rossetti, Gabriella M.K., Jamie H. Macdonald, Matthew Smith, Anna R. Jackson, Nigel Callender, Hannah K. Newcombe, Heather M. Storey, Sebastian Willis, Jojanneke van den Beukel, Jonathan Woodward, James Pollard, Benjamin Wood, Victoria Newton, Jana Virian, Owen Haswell, and Samuel J. Oliver. MEDEX2015: Greater sea-level fitness is associated with lower sense of effort during Himalayan trekking without worse acute mountain sickness. High Alt Med Biol. 18:152-162, 2017.-This study examined the complex relationships of fitness and hypoxic sensitivity with submaximal exercise responses and acute mountain sickness (AMS) at altitude. Determining these relationships is necessary before fitness or hypoxic sensitivity tests can be recommended to appraise individuals' readiness for altitude. Forty-four trekkers (26 men; 18 women; 20-67 years) completed a loaded walking test and a fitness questionnaire in normoxia to measure and estimate sea-level maximal aerobic capacity (maximum oxygen consumption [[Formula: see text]O2max]), respectively. Participants also completed a hypoxic exercise test to determine hypoxic sensitivity (cardiac, ventilatory, and arterial oxygen saturation responses to acute hypoxia, fraction of inspired oxygen [Fio2] = 0.112). One month later, all participants completed a 3-week trek to 5085 m with the same ascent profile. On ascent to 5085 m, ratings of perceived exertion (RPEascent), fatigue by Brunel Mood Scale, and AMS were recorded daily. At 5085 m, RPE during a fixed workload step test (RPEfixed) and step rate during perceptually regulated exercise (STEPRPE35) were recorded. Greater sea-level [Formula: see text]O2max was associated with, and predicted, lower sense of effort (RPEascent; r = -0.43; p < 0.001; RPEfixed; r = -0.69; p < 0.001) and higher step rate (STEPRPE35; r = 0.62; p < 0.01), but not worse AMS (r = 0.13; p = 0.4) or arterial oxygen desaturation (r = 0.07; p = 0.7). Lower RPEascent was also associated with better mood, including less fatigue (r = 0.57; p < 0.001). Hypoxic sensitivity was not associated with, and did not add to the prediction of submaximal exercise responses or AMS. In conclusion, participants with greater sea-level fitness reported less effort during simulated and actual trekking activities, had better mood (less fatigue), and chose a higher step rate during perceptually regulated exercise, but did not suffer from worse AMS or arterial oxygen desaturation. Simple sea-level fitness tests may be used to aid preparation for high-altitude travel.