Hyperpolarized 129Xe MRI, 99mTc scintigraphy, and SPECT in lung ventilation imaging: a quantitative comparison.

RATIONALE AND OBJECTIVES: The current clinical standard for functional imaging of patients with lung ailments is nuclear medicine scintigraphy and Single Photon Emission Computed Tomography (SPECT) which detect the gamma decay of inhaled radioactive tracers. Hyperpolarized (HP) Xenon-129 MRI (XeMRI) of the lungs has recently been FDA approved and provides similar functional images of the lungs with higher spatial resolution than scintigraphy and SPECT. Here we compare Technetium-99m (99mTc) diethylene-triamine-pentaacetate scintigraphy and SPECT with HP XeMRI in healthy controls, asthma, and chronic obstructive pulmonary disorder (COPD) patients. MATERIALS AND METHODS: 59 subjects, healthy, with asthma, and with COPD, underwent 99mTc scintigraphy/SPECT, standard spirometry, and HP XeMRI. XeMRI and SPECT images were registered for direct voxel-wise signal comparisons. Images were also compared using ventilation defect percentage (VDP), and a standard 6-compartment method. VDP calculated from XeMRI and SPECT images was compared to spirometry. RESULTS: Median Pearson correlation coefficient for voxel-wise signal comparison was 0.698 (0.613-0.782) between scintigraphy and XeMRI and 0.398 (0.286-0.502) between SPECT and XeMRI. Correlation between VDP measures was r = 0.853, p < 0.05. VDP separated asthma and COPD from the control group and was significantly correlated with FEV1, FEV1/FVC, and FEF 25-75. CONCLUSION: HP XeMRI provides equivalent information to 99mTc SPECT and standard spirometry measures. Additionally, XeMRI is non-invasive, hence it could be used for longitudinal studies for evaluating emerging treatment for lung ailments.

Optimizing Trajectories and Inverse Kinematics for Biomechanical Analysis of Markerless Motion Capture Data.

Markerless motion capture using computer vision and human pose estimation (HPE) has the potential to expand access to precise movement analysis. This could greatly benefit rehabilitation by enabling more accurate tracking of outcomes and providing more sensitive tools for research. There are numerous steps between obtaining videos to extracting accurate biomechanical results and limited research to guide many critical design decisions in these pipelines. In this work, we analyze several of these steps including the algorithm used to detect keypoints and the keypoint set, the approach to reconstructing trajectories for biomechanical inverse kinematics and optimizing the IK process. Several features we find important are: 1) using a recent algorithm trained on many datasets that produces a dense set of biomechanically-motivated keypoints, 2) using an implicit representation to reconstruct smooth, anatomically constrained marker trajectories for IK, 3) iteratively optimizing the biomechanical model to match the dense markers, 4) appropriate regularization of the IK process. Our pipeline makes it easy to obtain accurate biomechanical estimates of movement in a rehabilitation hospital.

Enhanced selectivity of transcutaneous spinal cord stimulation by multielectrode configuration.

Objective.Transcutaneous spinal cord stimulation (tSCS) has been gaining momentum as a non-invasive rehabilitation approach to restore movement to paralyzed muscles after spinal cord injury (SCI). However, its low selectivity limits the types of movements that can be enabled and, thus, its potential applications in rehabilitation.Approach.In this cross-over study design, we investigated whether muscle recruitment selectivity of individual muscles could be enhanced by multielectrode configurations of tSCS in 16 neurologically intact individuals. We hypothesized that due to the segmental innervation of lower limb muscles, we could identify muscle-specific optimal stimulation locations that would enable improved recruitment selectivity over conventional tSCS. We elicited leg muscle responses by delivering biphasic pulses of electrical stimulation to the lumbosacral enlargement using conventional and multielectrode tSCS.Results.Analysis of recruitment curve responses confirmed that multielectrode configurations could improve the rostrocaudal and lateral selectivity of tSCS. To investigate whether motor responses elicited by spatially selective tSCS were mediated by posterior root-muscle reflexes, each stimulation event was a paired pulse with a conditioning-test interval of 33.3 ms. Muscle responses to the second stimulation pulse were significantly suppressed, a characteristic of post-activation depression suggesting that spatially selective tSCS recruits proprioceptive fibers that reflexively activate muscle-specific motor neurons in the spinal cord. Moreover, the combination of leg muscle recruitment probability and segmental innervation maps revealed a stereotypical spinal activation map in congruence with each electrode's position.Significance. Improvements in muscle recruitment selectivity could be essential for the effective translation into stimulation protocols that selectively enhance single-joint movements in neurorehabilitation.

Enhanced selectivity of transcutaneous spinal cord stimulation by multielectrode configuration.

Objective: Transcutaneous spinal cord stimulation (tSCS) has been gaining momentum as a non-invasive rehabilitation approach to restore movement to paralyzed muscles after spinal cord injury (SCI). However, its low selectivity limits the types of movements that can be enabled and, thus, its potential applications in rehabilitation. Approach: In this cross-over study design, we investigated whether muscle recruitment selectivity of individual muscles could be enhanced by multielectrode configurations of tSCS in 16 neurologically intact individuals. We hypothesized that due to the segmental innervation of lower limb muscles, we could identify muscle-specific optimal stimulation locations that would enable improved recruitment selectivity over conventional tSCS. We elicited leg muscle responses by delivering biphasic pulses of electrical stimulation to the lumbosacral enlargement using conventional and multielectrode tSCS. Results: Analysis of recruitment curve responses confirmed that multielectrode configurations could improve the rostrocaudal and lateral selectivity of tSCS. To investigate whether motor responses elicited by spatially selective tSCS were mediated by posterior root-muscle reflexes, each stimulation event was a paired pulse with a conditioning-test interval of 33.3 ms. Muscle responses to the second stimulation pulse were significantly suppressed, a characteristic of post-activation depression suggesting that spatially selective tSCS recruits proprioceptive fibers that reflexively activate muscle-specific motor neurons in the spinal cord. Moreover, the combination of leg muscle recruitment probability and segmental innervation maps revealed a stereotypical spinal activation map in congruence with each electrode's position. Significance: Improvements in muscle recruitment selectivity could be essential for the effective translation into stimulation protocols that selectively enhance single-joint movements in neurorehabilitation.

Acute physiological responses to low-intensity blood flow restriction cycling.

OBJECTIVES: Blood flow restriction (BFR) during interval cycling may stimulate aerobic and anaerobic adaptations. However, acute physiological responses to BFR interval cycling have not been extensively investigated. DESIGN: Eighteen males completed low-intensity (LI), low-intensity with BFR (LIBFR) and high-intensity (HI) interval cycling sessions in randomised and counterbalanced order. These included a standardised warm-up and three two-min intervals interspersed with two-min recovery. Interval intensity during HI, LI and LIBFR were 85%, 40% and 40% of peak power output obtained during graded exercise tests. METHODS: During LIBFR, 80% arterial occlusion was applied to both legs during the interval efforts and removed during recovery. Continuous measures of heart rate (HR), cardiac output (CO) and oxygen consumption (V˙O2) were recorded. Blood pressure (BP) and rating of perceived exertion (RPE) were measured following intervals. Blood lactate concentration was measured pre- and post-exercise. RESULTS: BP, HR, CO, V˙O2, lactate and RPE were greatest during HI. During the active intervals, BP, HR and CO were greater during LIBFR than LI. V˙O2 during recovery periods were greater in LIBFR than LI. Post-session lactate was greater during LIBFR than LI. Importantly, mean arterial pressure during interval three was significantly greater in LIBFR (124±2mmHg) than HI (114±3mmHg). CONCLUSIONS: LIBFR increases cardiovascular and metabolic stress compared with LI and could provide an alternative aerobic training method for individuals unable to perform high-intensity exercise. However, increases in mean arterial pressure during LIBFR indicates high myocardial workload, and practitioners should therefore use caution if prescribing LIBFR for vascular compromised individuals.

Live high, train low - influence on resting and post-exercise hepcidin levels.

The post-exercise hepcidin response during prolonged (>2 weeks) hypoxic exposure is not well understood. We compared plasma hepcidin levels 3 h after exercise [6 × 1000 m at 90% of maximal aerobic running velocity (vVO2max )] performed in normoxia and normobaric hypoxia (3000 m simulate altitude) 1 week before, and during 14 days of normobaric hypoxia [196.2 ± 25.6 h (median: 200.8 h; range: 154.3-234.8 h) at 3000 m simulated altitude] in 10 well-trained distance runners (six males, four females). Venous blood was also analyzed for hepcidin after 2 days of normobaric hypoxia. Hemoglobin mass (Hbmass ) was measured via CO rebreathing 1 week before and after 14 days of hypoxia. Hepcidin was suppressed after 2 (Cohen's d = -2.3, 95% confidence interval: [-2.9, -1.6]) and 14 days of normobaric hypoxia (d = -1.6 [-2.6, -0.6]). Hepcidin increased from baseline, 3 h post-exercise in normoxia (d = 0.8 [0.2, 1.3]) and hypoxia (d = 0.6 [0.3, 1.0]), both before and after exposure (normoxia: d = 0.7 [0.3, 1.2]; hypoxia: d = 1.3 [0.4, 2.3]). In conclusion, 2 weeks of normobaric hypoxia suppressed resting hepcidin levels, but did not alter the post-exercise response in either normoxia or hypoxia, compared with the pre-exposure response.

Physical Demands of Sprinting in Professional Road Cycling.

The aim of this study was to quantify the demands of road competitions ending with sprints in male professional cycling. 17 races finished with top-5 results from 6 male road professional cyclists (age, 27.0±3.8 years; height, 1.76±0.03 m; weight, 71.7±1.1 kg) were analysed. SRM power meters were used to monitor power output, cadence and speed. Data were averaged over the entire race, different durations prior to the sprint (60, 10, 5 and 1 min) and during the actual sprint. Variations in power during the final 10 min of the race were quantified using exposure variation analysis. This observational study was conducted in the field to maximize the ecological validity of the results. Power, cadence and speed were statistically different between various phases of the race (p<0.001), increasing from 316±43 W, 95±4 rpm and 50.5±3.3 km·h(-1) in the last 10 min, to 487±58 W, 102±6 rpm and 55.4±4.7 km·h(-1) in the last min prior to the sprint. Peak power during the sprint was 17.4±1.7 W·kg(-1). Exposure variation analysis revealed a significantly greater number of short-duration high-intensity efforts in the final 5 min of the race, compared with the penultimate 5 min (p=0.010). These findings quantify the power output requirements associated with high-level sprinting in men's professional road cycling and highlight the need for both aerobic and anaerobic fitness.

Pacing, the missing piece of the puzzle to high-intensity interval training.

This study examined physiological and perceptual responses to matched work high-intensity interval training using all-out and 2 even-paced methodologies. 15 trained male cyclists performed 3 interval sessions of three 3-min efforts with 3 min of active recovery between efforts. The initial interval session was completed using all-out pacing, with the following 2 sessions being completed with computer- and athlete-controlled pacing in a randomised and semi-counterbalanced manner. Computer- and athlete-controlled intervals were completed at the mean power from the corresponding interval during the all-out trial. Oxygen consumption and ratings of perceived exertion were recorded during each effort. 20 min following each session, participants completed a 4-km time trial and provided sessional rating of perceived exertion. Oxygen consumption was greater during all-out (54.1±6.6 ml.kg(-1).min(-1); p<0.01) and athlete-controlled (53.0±5.8 ml.kg(-1).min(-1); p<0.01) compared with computer-controlled (51.5±5.7 ml.kg(-1).min(-1)). Total time ≥85% maximal oxygen consumption was greater during all-out compared to both even-paced efforts. Sessional ratings of perceived exertion were greater after all-out compared to both even-paced sessions. Mean 4-km power output was lower after all-out compared with both even paced intervals. Distribution of pace throughout high-intensity interval training can influence perceptual and metabolic stress along with subsequent performance and should be considered during the prescription of such training.

Physical activity and amyloid-ß plasma and brain levels: results from the Australian Imaging, Biomarkers and Lifestyle Study of Ageing.

Previous studies suggest physical activity improves cognition and lowers Alzheimer's disease (AD) risk. However, key AD pathogenic factors that are thought to be influenced by physical activity, particularly plasma amyloid-ß (Aß) and Aß brain load, have yet to be thoroughly investigated. The objective of this study was to determine if plasma Aß and amyloid brain deposition are associated with physical activity levels, and whether these associations differed between carriers and non-carriers of the apolipoprotein E (APOE) ε4 allele. Five-hundred and forty six cognitively intact participants (aged 60-95 years) from the Australian Imaging, Biomarkers and Lifestyle Study of Ageing (AIBL) were included in these analyses. Habitual physical activity levels were measured using the International Physical Activity Questionnaire (IPAQ). Serum insulin, glucose, cholesterol and plasma Aß levels were measured in fasting blood samples. A subgroup (n=116) underwent (11)C-Pittsburgh compound B (PiB) positron emission tomography (PET) scanning to quantify brain amyloid load. Higher levels of physical activity were associated with higher high density lipoprotein (HDL) (P=0.037), and lower insulin (P<0.001), triglycerides (P=0.019) and Aß1-42/1-40 ratio (P=0.001). After stratification of the cohort based on APOE ε4 allele carriage, it was evident that only non-carriers received the benefit of reduced plasma Aß from physical activity. Conversely, lower levels of PiB SUVR (standardised uptake value ratio) were observed in higher exercising APOE ε4 carriers. Lower plasma Aß1-42/1-40 and brain amyloid was observed in those reporting higher levels of physical activity, consistent with the hypothesis that physical activity may be involved in the modulation of pathogenic changes associated with AD.

Multiple effects of physical activity on molecular and cognitive signs of brain aging: can exercise slow neurodegeneration and delay Alzheimer's disease?

Western countries are experiencing aging populations and increased longevity; thus, the incidence of dementia and Alzheimer's disease (AD) in these countries is projected to soar. In the absence of a therapeutic drug, non-pharmacological preventative approaches are being investigated. One of these approaches is regular participation in physical activity or exercise. This paper reviews studies that have explored the relationship between physical activity and cognitive function, cognitive decline, AD/dementia risk and AD-associated biomarkers and processes. There is now strong evidence that links regular physical activity or exercise to higher cognitive function, decreased cognitive decline and reduced risk of AD or dementia. Nevertheless, these associations require further investigation, more specifically with interventional studies that include long follow-up periods. In particular, relatively little is known about the underlying mechanism(s) of the associations between physical activity and AD neuropathology; clearly this is an area in need of further research, particularly in human populations. Although benefits of physical activity or exercise are clearly recognised, there is a need to clarify how much physical activity provides the greatest benefit and also whether people of different genotypes require tailored exercise regimes.

Intense physical activity is associated with cognitive performance in the elderly.

Numerous studies have reported positive impacts of physical activity on cognitive function. However, the majority of these studies have utilised physical activity questionnaires or surveys, thus results may have been influenced by reporting biases. Through the objective measurement of routine levels of physical activity via actigraphy, we report a significant association between intensity, but not volume, of physical activity and cognitive functioning. A cohort of 217 participants (aged 60-89 years) wore an actigraphy unit for 7 consecutive days and underwent comprehensive neuropsychological assessment. The cohort was stratified into tertiles based on physical activity intensity. Compared with individuals in the lowest tertile of physical activity intensity, those in the highest tertile scored 9%, 9%, 6% and 21% higher on the digit span, digit symbol, Rey Complex Figure Test (RCFT) copy and Rey Figure Test 30-min recall test, respectively. Statistically, participants in the highest tertile of physical activity intensity performed significantly better on the following cognitive tasks: digit symbol, RCFT copy and verbal fluency test (all P<0.05). The results indicate that intensity rather than quantity of physical activity may be more important in the association between physical activity and cognitive function.

Reliability/Validity of the fortius trainer.

This study examined the reliability/validity of power output measured using the Fortius Virtual Reality cycle trainer. 10 cyclists (age: 28±6 years; V˙O (2)max: 60.9±7.2 ml · kg (-1) · min (-1); peak power: 393±82 W) completed three 20 km time trials on a Fortius cycle trainer. During each time trial, power output was measured at 1 Hz using the Fortius internal software and a PowerTap power monitor. Validity calculated for the Fortius trainer; Pearson correlation coefficient (r=0.99; 95% CI: 0.98-0.99; p<0.01) and typical error of estimate (3.5%; 95% CI: 3.2-3.9%), was similar to other established laboratory ergometers. No differences (F (2,16)=0.32; p=0.73) in mean 20 km power were observed between trial 1 (253±46 W), 2 (258±49 W), or 3 (255±50 W). Test-retest reliability (intraclass correlation coefficient (ICC) and coefficient of variation (CV)) was better between trial 2 and 3 (ICC=1.00 (CI: 0.98-1.00); CV: 1.6% (CI: 1.1-3.3%)) compared with trial 1 and 2 (ICC=0.98 (CI: 0.91-1.00); CV: 3.3% (CI: 2.2-6.4%)). The Fortius cycle trainer is a valid and reliable device for the measurement of power output in cyclists, thus providing an alternative to larger more expensive laboratory ergometers.

Effect of a 5-min cold-water immersion recovery on exercise performance in the heat.

BACKGROUND: This study examined the effect of a 5-min cold-water immersion (14 degrees C) recovery intervention on repeated cycling performance in the heat. METHODS: 10 male cyclists performed two bouts of a 25-min constant-paced (254 (22) W) cycling session followed by a 4-km time trial in hot conditions (35 degrees C, 40% relative humidity). The two bouts were separated by either 15 min of seated recovery in the heat (control) or the same condition with 5-min cold-water immersion (5th-10th minute), using a counterbalanced cross-over design (CP(1)TT(1) --> CWI or CON --> CP(2)TT(2)). Rectal temperature was measured immediately before and after both the constant-paced sessions and 4-km timed trials. Cycling economy and Vo(2) were measured during the constant-paced sessions, and the average power output and completion times were recorded for each time trial. RESULTS: Compared with control, rectal temperature was significantly lower (0.5 (0.4) degrees C) in cold-water immersion before CP(2) until the end of the second 4-km timed trial. However, the increase in rectal temperature (0.5 (0.2) degrees C) during CP(2) was not significantly different between conditions. During the second 4-km timed trial, power output was significantly greater in cold-water immersion (327.9 (55.7) W) compared with control (288.0 (58.8) W), leading to a faster completion time in cold-water immersion (6.1 (0.3) min) compared with control (6.4 (0.5) min). Economy and Vo(2) were not influenced by the cold-water immersion recovery intervention. CONCLUSION: 5-min cold-water immersion recovery significantly lowered rectal temperature and maintained endurance performance during subsequent high-intensity exercise. These data indicate that repeated exercise performance in heat may be improved when a short period of cold-water immersion is applied during the recovery period.

Influence of starting strategy on cycling time trial performance in the heat.

The purpose of this study was to determine the influence of starting strategy on time trial performance in the heat. Eleven endurance trained male cyclists (30+/-5 years, 79.5+/-4.6 kg, VO(2max) 58.5+/-5.0 ml x kg x (-1) min(-1)) performed four 20-km time trials in the heat (32.7+/-0.7 degrees C and 55% relative humidity). The first time trial was completed at a self-selected pace (SPTT). During the following time trials, subjects performed the initial 2.5-km at power outputs 10% above (10% ATT), 10% below (10% BTT) or equal (ETT) to that of the average power during the initial 2.5-km of the self-selected trial; the remaining 17.5-km was self-paced. Throughout each time trial, power output, rectal temperature, skin temperature, heat storage, pain intensity and thermal sensation were taken. Despite significantly (P<0.05) greater power outputs for 10% BTT (273+/-45W) compared with the ETT (267+/-48W) and 10% ATT (265+/-41W) during the final 17.5-km, overall 20-km performance time was not significantly different amongst trials. There were no differences in any of the other measured variables between trials. These data show that varying starting power by +/-10% did not affect 20 km time trial performance in the heat.

Effect of cold water immersion on postexercise parasympathetic reactivation.

The aim of the present study was to assess the effect of cold water immersion (CWI) on postexercise parasympathetic reactivation. Ten male cyclists (age, 29 +/- 6 yr) performed two repeated supramaximal cycling exercises (SE(1) and SE(2)) interspersed with a 20-min passive recovery period, during which they were randomly assigned to either 5 min of CWI in 14 degrees C or a control (N) condition where they sat in an environmental chamber (35.0 +/- 0.3 degrees C and 40.0 +/- 3.0% relative humidity). Rectal temperature (T(re)) and beat-to-beat heart rate (HR) were recorded continuously. The time constant of HR recovery (HRRtau) and a time (30-s) varying vagal-related HR variability (HRV) index (rMSSD(30s)) were assessed during the 6-min period immediately following exercise. Resting vagal-related HRV indexes were calculated during 3-min periods 2 min before and 3 min after SE(1) and SE(2). Results showed no effect of CWI on T(re) (P = 0.29), SE performance (P = 0.76), and HRRtau (P = 0.61). In contrast, all vagal-related HRV indexes were decreased after SE(1) (P < 0.001) and tended to decrease even further after SE(2) under N condition but not with CWI. When compared with the N condition, CWI increased HRV indexes before (P < 0.05) and rMSSD(30s) after (P < 0.05) SE(2). Our study shows that CWI can significantly restore the impaired vagal-related HRV indexes observed after supramaximal exercise. CWI may serve as a simple and effective means to accelerate parasympathetic reactivation during the immediate period following supramaximal exercise.

Julius Hallervorden's wartime activities: implications for science under dictatorship.

The eponym Hallervorden-Spatz syndrome recalls Julius Hallervorden's and Hugo Spatz's original description of this pediatric neurodegenerative disorder. Julius Hallervorden's important contribution to the practice of neuropathology over a long career cannot be underestimated. However, his work as a pathologist during the Third Reich put him in close proximity with the implementation of biologic solutions (i.e., euthanasia) targeting those individuals with significant intellectual or physical disabilities in chronic-care facilities. The Nazi program of active euthanasia provided a scientific opportunity to gain quick access to pathologic materials. This opportunity was recognized and used by Hallervorden to achieve personal scientific objectives and research efforts. These efforts resulted in a number of postwar scientific publications using materials obtained through the euthanasia program. The participation of distinguished academic physicians in such a program provides a cautionary tale of the potential results of ethical compromise and the effects of the abrogation of personal autonomy in the setting of a totalitarian dictatorship.

Hans-Joachim Scherer (1906-1945), pioneer in glioma research.

Hans-Joachim Scherer was among the most creative and productive neuropathologists of his time. Working as a political refugee in Antwerp (Belgium) during 1934-41, he published landmark papers on the morphology and biology of malignant gliomas, and was the first to clearly distinguish primary and secondary glioblastomas, and growth patterns reflecting the invasion of preexisting brain tissue (secondary structures). Scherer was a controversial personality, who at the end of World War II became entangled in the Nazi euthanasia programme.

[Neurology in the "3rd Reich" and consequences]. / Zur Neurologie im "Dritten Reich" und ihren Nachwirkungen.

This review of German neurology during the Nazi era mentions first the significance of Jewish neurologists for the history of the specialty, and the irreplaceable loss that their expulsion from Germany represented. A brief discussion of the scientific accomplishments of German neurologists during this time is followed by a description of violations of ethical principles, exemplified by the human experiments of G. Schaltenbrand. The spirit of the age exerted a malevolent influence.