Holmes, David R.

Background Despite improvements in military aircraft safety, many aviation incidents are attributed to hypoxia. The correlation between moderate hypoxia and cognitive function are well studied but results remain controversial. Comparatively, the effects of severe hypoxia are still not well understood. In the present study, we examined the executive cognitive function and physiological indices under both moderate and severe hypoxia conditions. Purpose To examine the relationship between executive function and physiological indices during acute hypoxia exposure. Methods Ten young healthy participants (4M/6F, 29±4 years) completed two different levels of hypoxia: 1) 10 minute moderate hypoxia (MH; F i O 2 = 0.118) and 2) 3 minute severe hypoxia (SH; F i O 2 = 0.077) following 3 minute baseline (BL; F i O 2 =0.209). Reaction time and errors of commission (defined as a response to a non‐target stimulus) were evaluated continuously using a custom Go/No‐go test at baseline and throughout hypoxia exposure. In this Go/No‐go test, participants were required to push a key when upper case “A” or “@” appeared but not when lower case “a” appeared on a computer monitor as quick and as accurately as possible. The stimuli were presented one at a time at any one of nine differing locations across the screen. Cerebral oxygenation (rSO 2 ) was continuously monitored with near‐infrared spectroscopy (NIRS) positioned above the left supraorbital ridge. Finger oxygen saturation (S p O 2 ) was continuously assessed using a pulse oximetry. Data were analyzed in every 30 seconds and are presented as mean±SE. Two‐way ANOVA and Bonferroni test for multiple comparisons was used to evaluate significant differences. Results Both S p O 2 and rSO 2 were reduced with SH (S p O 2 %, BL: 99.3±0.1% vs. SH: 70.7±1.5%, P<0.01; rSO 2 %, BL: 70±4% vs. SH: 58±4%, P<0.01). In SH, correlations of S p O 2 and rSO 2 were significant to the number of errors during the cognitive performance task (S p O 2 ; R= −0.65, rSO 2 ; R= −0.58, Both P<0.01). SH significantly increased errors of commission of the last 30 seconds in 3 minute hypoxic exposure. (BL: 0.6±0.2 errors vs. SH: 1.7±0.5 errors, P<0.01). SH significantly decreased reaction time over hypoxic exposure (BL: 0.43±0.01 sec vs. SH: 0.41±0.01 sec, P<0.01). Comparatively, MH did not elicit an increase in the number of errors of commission nor a decrease in reaction time (Both, P>0.05). Conclusion Executive function deteriorated during severe hypoxia. Oxygenation of the prefrontal lobe which controls inhibition may be related to the increase in commission errors. Devices that monitor physiological indices such as S p O 2 or rSO 2 might be beneficial for a model to predict executive deterioration. Support or Funding Information This project was funded by the Office of Naval Research (ONR), grant number N00014‐18‐D‐7001‐TO1.

Background Cognitive deficits resulting from mild hypoxia are difficult to quantify and reproduce consistently. The changes in executive function during acute hypoxia are still controversial. The purpose of present study was to assess changes in executive function during acute moderate hypoxia using a continuous performance test (Connors’ Continuous Performance test, CCPT‐II). Methods Nine young, healthy adults (7 women; 28 ± 1 years; BMI: 24.5 ± 3.0 kg·m −2 ) performed two sets of CCPT‐II during two different conditions: 1) 7 minutes of baseline (fraction of inspired oxygen (F i O 2 ) = 0.21) and 2) 10 minutes of hypoxia (F i O 2 =0.118). The CCPT‐II is a test of executive cognitive function which requires subjects to strike a key when any letter except the letter X appeared on a computer monitor as quickly and accurately as possible. Reaction time, commission errors (response to X), and omission errors (failure to respond to a letter other than X) were recorded for each 140s of the CCPT‐II block. Arterial oxygen concentration (P a O 2 ) was measured during the last 30sec of baseline and hypoxia from brachial artery catheter samples. Results P a O 2 was reduced in hypoxia ( baseline : 103.1 ± 1.5 mmHg vs. hypoxia : 43.2 ± 1.0 mmHg, P <0.01). During the trials of the CCPT‐II performed during hypoxia, reaction time was lower (i.e. faster) than during baseline ( baseline : 451 ± 18 ms. vs. hypoxia : 437 ± 13 ms., P<0.01). Additionally, the number of commission errors was greater in hypoxia ( baseline : 1.3 ± 0.6 errors·block −1 vs. hypoxia : 2.1 ± 0.8 errors·block −1 , P<0.01). However, the number of omission errors was not different between the two conditions ( baseline : 0.4 ± 0.2 errors·block −1 vs. hypoxia : 0.2 ± 0.1 errors·block −1 , P=0.92). Conclusions The number of commission errors increased and the reaction time decreased during the CCPT‐II test performed in moderate hypoxia compared to baseline, demonstrating a decline in cognitive function during hypoxia. The faster and less accurate responses during hypoxia suggest a suppression of inhibitory pathways in the prefrontal or motor cortex that may contribute to the observed acute reduction in executive cognitive function. Support or Funding Information This project was funded by the Office of Naval Research (ONR), grant number N00014‐18‐D‐7001‐TO1.

Purpose Using common datasets, to estimate and compare the diagnostic performance of image‐based denoising techniques or iterative reconstruction algorithms for the task of detecting hepatic metastases. Methods Datasets from contrast‐enhanced CT scans of the liver were provided to participants in an NIH ‐, AAPM ‐ and Mayo Clinic‐sponsored Low Dose CT Grand Challenge. Training data included full‐dose and quarter‐dose scans of the ACR CT accreditation phantom and 10 patient examinations; both images and projections were provided in the training data. Projection data were supplied in a vendor‐neutral standardized format ( DICOM ‐ CT ‐ PD ). Twenty quarter‐dose patient datasets were provided to each participant for testing the performance of their technique. Images were provided to sites intending to perform denoising in the image domain. Fully preprocessed projection data and statistical noise maps were provided to sites intending to perform iterative reconstruction. Upon return of the denoised or iteratively reconstructed quarter‐dose images, randomized, blinded evaluation of the cases was performed using a Latin Square study design by 11 senior radiology residents or fellows, who marked the locations of identified hepatic metastases. Markings were scored against reference locations of clinically or pathologically demonstrated metastases to determine a per‐lesion normalized score and a per‐case normalized score (a faculty abdominal radiologist established the reference location using clinical and pathological information). Scores increased for correct detections; scores decreased for missed or incorrect detections. The winner for the competition was the entry that produced the highest total score (mean of the per‐lesion and per‐case normalized score). Reader confidence was used to compute a Jackknife alternative free‐response receiver operating characteristic ( JAFROC ) figure of merit, which was used for breaking ties. Results 103 participants from 90 sites and 26 countries registered to participate. Training data were shared with 77 sites that completed the data sharing agreements. Subsequently, 41 sites downloaded the 20 test cases, which included only the 25% dose data ( CTDI vol = 3.0 ± 1.8 mG y, SSDE = 3.5 ± 1.3 mG y). 22 sites submitted results for evaluation. One site provided binary images and one site provided images with severe artifacts; cases from these sites were excluded from review and the participants removed from the challenge. The mean (range) per‐lesion and per‐case normalized scores were −24.2% (−75.8%, 3%) and 47% (10%, 70%), respectively. Compared to reader results for commercially reconstructed quarter‐dose images with no noise reduction, 11 of the 20 sites showed a numeric improvement in the mean JAFROC figure of merit. Notably two sites performed comparably to the reader results for full‐dose commercial images. The study was not designed for these comparisons, so wide confidence intervals surrounded these figures of merit and the results should be used only to motivate future testing. Conclusion Infrastructure and methodology were developed to rapidly estimate observer performance for liver metastasis detection in low‐dose CT examinations of the liver after either image‐based denoising or iterative reconstruction. The results demonstrated large differences in detection and classification performance between noise reduction methods, although the majority of methods provided some improvement in performance relative to the commercial quarter‐dose images with no noise reduction applied.

Background Detection of small renal calculi has benefitted from recent advances in computed tomography (CT) scanner design. Information regarding observer performance when using state-of-the-art CT scanners for this application is needed. Purpose To assess observer performance and the impact of radiation dose for detection and size measurement of <4 mm renal stones using CT with integrated circuit detectors and iterative reconstruction. Material and Methods Twenty-nine <4 mm calcium oxalate stones were randomly placed in 20 porcine kidneys in an anthropomorphic phantom. Four radiologists used a workstation to record each calculus detection and size. JAFROC Figure of Merit (FOM), sensitivity, false positive detections, and calculus size were calculated. Results Mean calculus size was 2.2 ± 0.7 mm. The CTDI vol values corresponding to the automatic exposure control settings of 160, 80, 40, 25, and 10 Quality Reference mAs (QRM) were 15.2, 7.9, 4.2, 2.7, and 1.3 mGy, respectively. JAFROC FOM was ≥ 0.97 at ≥ 80 QRM, ≥ 0.89 at ≥ 25 QRM, and was inferior to routine dose (160 QRM) at 10 QRM (0.72, P < 0.05). Per-calculus sensitivity remained ≥ 85% for every reader at ≥ 25 QRM. Mean total false positive detections per reader were ≤ 3 at ≥ 80 QRM, but increased substantially for two readers ( ≥ 12) at ≤ 40 QRM. Measured calculus size significantly decreased at ≤ 25 QRM ( P ≤ 0.01). Conclusion Using low dose renal CT with iterative reconstruction and ≥ 25 QRM results in high sensitivity, but false positive detections increase for some readers at very low dose levels (≤ 40 QRM). At very low doses with iterative reconstruction, measured calculus size will artifactually decrease.

Background— Sex-specific differences affect the evaluation, treatment, and prognosis of coronary artery disease. We tested the hypothesis that long-term outcomes of fractional flow reserve (FFR)–guided percutaneous coronary intervention (PCI) are different between women and men. Methods and Results— Consecutive 1090 patients, referred for PCI and undergoing FFR measurements at the Mayo Clinic between October 2002 and December 2009, were included in this registry study. Clinical events were compared between the sexes during a median follow-up of 50.9 months. Of all patients, women had higher FFR adjusted by visual coronary stenosis than men ( P =0.03). The Kaplan–Meier percent of major adverse cardiac events at 5 years was 35% in women and 38% in men ( P =0.54). Interestingly, in patients undergoing PCI with an FFR <0.75, the incidence of death or myocardial infarction was significantly higher in women than in men (hazard ratio, 2.16; 95% confidence interval, 1.04–4.51; P =0.04). Moreover, compared with patients with FFR >0.80, deferral of PCI for those with FFR between 0.75 and 0.80 was associated with an increased rate of major adverse cardiac events, particularly death or myocardial infarction in women (hazard ratio, 3.25; 95% confidence interval, 1.56–6.74; P =0.002) and revascularization in men (hazard ratio, 2.66; 95% confidence interval, 1.66–4.54; P <0.001). Conclusions— Long-term outcome differs between women and men undergoing FFR-guided PCI. Our data suggest that the sex-based treatment strategy is necessary to further optimize prognosis of patients with coronary artery disease.