Nasopharyngeal method for selective brain cooling and development of a time-resolved near-infrared technique to monitor brain temperature and oxidation status during hypothermia

Mild hypothermia at 32-35oC (HT) has been shown to be neuroprotective for neurological emergencies following severe head trauma, cardiac arrest and neonatal asphyxia. However, HT has not been widely deployed in clinical settings because: firstly, cooling the whole body below 33-34°C can induce severe complications; therefore, applying HT selectively to the brain could minimize adverse effects by maintaining core body temperature at normal level. Secondly, development of an effective and easy to implement selective brain cooling (SBC) technique, which can quickly induce brain hypothermia while avoiding complications from whole body cooling, remains a challenge. In this thesis, we studied the feasibility and efficiency of selective brain cooling (SBC) through nasopharyngeal cooling. To control the cooling and rewarming rate and because core body temperature is different from brain temperature, we also developed a non-invasive technique based on time-resolved near infrared spectroscopy (TR-NIRS) to measure local brain temperature. In normal brain, cerebral blood flow (CBF) and energy metabolism as reflected by the cerebral metabolic rate of oxygen (CMRO2) is tightly coupled leading to an oxygen extraction efficiency (OEF) of around ~33%. A decoupling of the two as in ischemia signifies oxidative stress and would lead to an increase in OEF beyond the normal value of ~33%. The final goal of this thesis is to evaluate TR-NIRS methods for measurements of CBF and CMRO2 to monitor for oxidative metabolism in the brain with and without HT treatment. Chapter 2 presents investigations on the feasibility and efficiency of the nasopharyngeal SBC by blowing room temperature or humidified cooled air into the nostrils. Effective brain cooling at a median cooling rate of 5.6 ± 1.1°C/hour compared to whole body cooling rate of 3.2 ± 0.7 was demonstrated with the nasopharyngeal cooling method. Chapter 3 describes TR-NIRS experiments performed to measure brain temperature non-invasively based on the temperature-dependence of the water absorption peaks at ~740 and 840nm. The TR-NIRS method was able to measure brain temperature with a mean difference of 0.5 ± 1.6°C (R2 = 0.66) between the TR-NIRS and thermometer measurements. Chapter 4 describes the TR-NIR technique developed to measure CBF and CMRO2 in a normoxia animal model under different anesthetics at different brain temperatures achieved by whole-body cooling. Both CBF and CMRO2 decreased with decreasing brain temperature but the ratio CMRO2:CBF (OEF) remained unchanged around the normal value of ~33%. These results demonstrate that TR-NIR can be used to monitor the oxidative status of the brain in neurological emergencies and its response to HT treatment. In summary, this thesis has established a convenient method for selective brain cooling without decreasing whole body temperature to levels when adverse effects could be triggered. TR-NIRS methods are also developed for monitoring local brain temperature to guide SBC treatment and for monitoring the oxidation status of the brain as treatment progresses

Non-invasive Monitoring of Brain Temperature during Rapid Selective Brain Cooling by Zero-Heat-Flux Thermometry

Introduction: Selective brain cooling can minimize systemic complications associated with whole body cooling but maximize neuroprotection. Recently, we developed a non-invasive, portable and inexpensive system for selectively cooling the brain rapidly and demonstrated its safety and efficacy in porcine models. However, the widespread application of this technique in the clinical setting requires a reliable, non-invasive and accurate method for measuring local brain temperature so that cooling and rewarming rates can be controlled during targeted temperature management. In this study, we evaluate the ability of a zero-heat-flux SpotOn sensor, mounted on three different locations, to measure brain temperature during selective brain cooling in a pig model. Computed Tomography (CT) was used to determine the position of the SpotOn patches relative to the brain at different placement locations. Methods and Results: Experiments were conducted on two juvenile pigs. Body temperature was measured using a rectal temperature probe while brain temperature with an intraparenchymal thermocouple probe. A SpotOn patch was taped to the pig’s head at three different locations: 1-2 cm posterior (Location #1, n=1), central forehead (Location #2, n=1); and 1-2 cm anterior and lateral to the bregma i.e., above the eye on the forehead (Location #3, n=1). This cooling system was able to rapidly cool the brain temperature to 33.7 ± 0.2°C within 15 minutes, and maintain the brain temperature within 33-34°C for 4-6 hours before slowly rewarming to 34.8 ± 1.1°C from 33.7 ± 0.2°C, while maintaining the core body temperature (as per rectal temperature probe) above 36°C. We measured a mean bias of -1.1°C, -0.2°C and 0.7°C during rapid cooling in induction phase, maintenance and rewarming phase, respectively. Amongst the three locations, location #2 had the highest correlation (R2 = 0.8) between the SpotOn sensor and the thermocouple probe. Conclusions: This SBC method is able to tightly control the rewarming rate within 0.52 ± 0.20°C/h. The SpotOn sensor placed on the center of the forehead provides a good measurement of brain temperature in comparison to the invasive needle probe

A novel selective cooling system for the brain: feasibility study in rabbits vs piglets

Abstract Background Selective brain cooling (SBC) methods could alleviate the complications associated with systemic hypothermia. The authors (MFB, LK, and T-YL) have developed a simple and an effective nasopharyngeal SBC method using a vortex tube. The primary focus of the study is to evaluate the effectiveness of this approach on rabbits and compare it with our previous published finding on piglets, which are mammals without and with a carotid rete, respectively. Methods Experiments were conducted on six rabbits. Body temperature was measured continuously using an esophageal temperature probe while brain temperature was measured with an implanted thermometer. Two successive experiments were performed on each animal. In the first experiment, brain cooling was initiated by blowing room temperature air from the hospital medical air outlet, at a flow rate of 14–15 L/min into both nostrils for 60 min. The second series of measurements and brain cooling was performed in the same manner as the first one but blowing cold air (− 7 °C) at the same flow rate. Results One hour post cooling with room temperature air at a flow rate of 14–15 L/min, the brain temperature was 34.2 ± 1.2 °C which resulted in mean brain cooling rates of 3.7 ± 0.9 °C/h. Brain temperature could be reduced more rapidly at mean rates of 5.2 ± 1.9 °C/h, while the body temperature as measured by the esophageal temperature probe was maintained above 36 °C during cooling and maintaining period. Conclusions We have demonstrated that using the vortex tube allows initial rapid and SBC in rabbits. Moreover, comparing results between piglets and rabbits demonstrates clearly that the lack of a carotid rete does not prevent specific cooling of the brain by means of the nasopharyngeal method

Selective head–neck cooling after concussion shortens return-to-play in ice hockey players

We aimed to investigate whether selective head–neck cooling could shorten recovery after sports-related concussions (SRCs). In a nonrandomized study of 15 Swedish professional ice hockey teams, 29 concussed players received immediate head and neck cooling for ≥30 min (initiated at 12.3 ± 9.2 min post-SRC by a portable cooling system), and 52 SRC controls received standard management. Players receiving head–neck cooling had shorter time to return-to-play than controls (7 vs 12.5 days, p < 0.0001), and 7% in the intervention group versus 25% in the control group were out of play for ≥3 weeks (p = 0.07). Immediate selective head–neck cooling is a promising option in the acute management of SRC that should be addressed in larger cohorts

Impacto de la estabilidad en el rendimiento de los clubes de fútbol de la Copa del Golfo Pérsico

The objective of this study was to determine the impact of sta-bility/instability on the performance of Persian Gulf Pro League football clubs. All the clubs that had participated in more than 3 seasons of the last 17 seasons (2001-2019) of the Persian Gulf Pro League were analyzed in this study (n=26). The performance of each team (improvement or worse-ning in ranking) and their stability were analyzed year after year in the pe-riod 2001-2019. The stability was divided in four components: CEO, head coach, players and club. The statistical analysis was performed with the software SPSS. Stability significantly (p<0.05) increased performance and instability significantly (p<0.05) decreased performance of the clubs in the four components studied: CEO, head coach, players and club. Therefore, it is expected that the results of this study encourage Iranian football clubs to increase their stabilityResumen: El objetivo de este estudio fue determinar el impacto de la estabilidad/inestabilidad en el rendimiento de los clubes de fútbol de la Copa del Golfo Pérsico. Todos los clubes que habían participado en más de 3 temporadas de las últimas 17 temporadas (2001-2019) de la Copa del Golfo Pérsico fueron analizados en este estudio (n=26). El rendimiento de cada equipo (mejora o empeoramiento en el ranking) y su estabilidad se analizaron año tras año en el período 2001-2019. La estabilidad se dividió en cuatro componentes: director, entrenador, jugadores y club. El análisis estadístico se realizó con el software SPSS. La estabilidad aumentó significativamente (p<0.05) el rendimiento y la inestabilidad disminuyó significativamente (p<0.05) el rendimiento de los clubes en los cuatro componentes estudiados: director, entrenador, jugadores y club. Por lo tanto, se espera que los resultados de este estudio animen a los clubes de fútbol iraníes a aumentar su estabilidad

Monitoring brain temperature by time-resolved near-infrared spectroscopy: Pilot study

Mild hypothermia (HT32°CX33°C) is an effective neuroprotective strategy for a variety of acute brain injuries. However, the wide clinical adaptation of HT32°C?33°C has been hampered by the lack of a reliable noninvasive method for measuring brain temperature, since core measurements have been shown to not always reflect brain temperature. The goal of this work was to develop a noninvasive optical technique for measuring brain temperature that exploits both the temperature dependency of water absorption and the high concentration of water in brain (80%-90%). Specifically, we demonstrate the potential of time-resolved near-infrared spectroscopy (TR-NIRS) to measure temperature in tissue-mimicking phantoms (in vitro) and deep brain tissue (in vivo) during heating and cooling, respectively. For deep brain tissue temperature monitoring, experiments were conducted on newborn piglets wherein hypothermia was induced by gradual whole body cooling. Brain temperature was concomitantly measured by TR-NIRS and a thermocouple probe implanted in the brain. Our proposed TRNIRS method was able to measure the temperature of tissue-mimicking phantoms and brain tissues with a correlation of 0.82 and 0.66 to temperature measured with a thermometer, respectively. The mean difference between the TR-NIRS and thermometer measurements was 0.15°C ± 1.1°C for the in vitro experiments and 0.5°C ± 1.6°C for the in vivo measurements. ©2014 Society of Photo-Optical Instrumentation Engineers

Shorter Recovery Time in Concussed Elite Ice Hockey Players by Early Head-and-Neck Cooling : A Clinical Trial

A sports-related concussion (SRC) is most commonly sustained in contact sports, and is defined as a mild traumatic brain injury. An exercise-induced elevation of core body temperature is associated with increased brain temperature that may accelerate secondary injury processes following SRC, and exacerbate the brain injury. In a recent pilot study, acute head-neck cooling of 29 concussed ice hockey players resulted in shorter time to return-to-play. Here, we extended the clinical trial to include players of 19 male elite Swedish ice hockey teams over five seasons (2016-2021). In the intervention teams, acute head-neck cooling was implemented using a head cap for ≥45 min in addition to the standard SRC management used in controls. The primary endpoint was time from SRC until return-to-play (RTP). Sixty-one SRCs were included in the intervention group and 71 SRCs in the control group. The number of previous SRCs was 2 (median and interquartile range [IQR]: 1.0-2.0) and 1 (IQR 1.0-2.0) in the intervention and control groups, respectively; p = 0.293. Median time to initiate head-neck cooling was 10 min (IQR 7-15; range 5-30 min) and median duration of cooling was 45 min (IQR 45-50; range 45-70 min). The median time to RTP was 9 days in the intervention group (IQR 7.0-13.5 days) and 13 days in the control group (IQR 9-30; p < 0.001). The proportion of players out from play for more than the expected recovery time of 14 days was 24.7% in the intervention group, and 43.7% in controls (p < 0.05). Study limitations include that: 1) allocation to cooling or control management was at the discretion of the medical staff of each team, decided prior to each season, and not by strict randomization; 2) no sham cap was used and evaluations could not be performed by blinded assessors; and 3) it could not be established with certainty that injury severity was similar between groups. While the results should thus be interpreted with caution, early head-neck cooling, with the aim of attenuating cerebral hyperthermia, may reduce post-SRC symptoms and lead to earlier return-to-play in elite ice hockey players

Coupling of cerebral blood flow and oxygen consumption during hypothermia in newborn piglets as measured by time-resolved near-infrared spectroscopy: A pilot study

© 2015 Society of Photo-Optical Instrumentation Engineers (SPIE). Hypothermia (HT) is a potent neuroprotective therapy that is now widely used in following neurological emergencies, such as neonatal asphyxia. An important mechanism of HT-induced neuroprotection is attributed to the associated reduction in the cerebral metabolic rate of oxygen (CMRO2). Since cerebral circulation and metabolism are tightly regulated, reduction in CMRO2 typically results in decreased cerebral blood flow (CBF); it is only under oxidative stress, e.g., hypoxia-ischemia, that oxygen extraction fraction (OEF) deviates from its basal value, which can lead to cerebral dysfunction. As such, it is critical to measure these key physiological parameters during therapeutic HT. This report investigates a noninvasive method of measuring the coupling of CMRO2 and CBF under HT and different anesthetic combinations of propofol/nitrous-oxide (N2O) that may be used in clinical practice. Both CBF and CMRO2 decreased with decreasing temperature, but the OEF remained unchanged, which indicates a tight coupling of flow and metabolism under different anesthetics and over the mild HT temperature range (38°C to 33°C)