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).
KEYWORDS: Temperature metrology, Brain, Absorption, Tissues, Near infrared spectroscopy, Tissue optics, Calibration, Optical properties, In vivo imaging, Scattering
Mild hypothermia (HT32°C−33°C) is an effective neuroprotective strategy for a variety of acute brain injuries. However, the wide clinical adaptation of HT32−33°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 TR-NIRS 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.
Mild hypothermia (HT), in which the brain is cooled to 32-33°C, has been shown to be neuroprotective for neurological emergencies such as head trauma and neonatal asphyxia. Xenon (Xe), a scarce and expensive anesthetic gas, has also shown great promise as a neuroprotectant, particularly when combined with HT. The purpose of the present study was to investigate the combined effect of Xe and HT on the cerebral metabolic rate of oxygen (CMRO2) and cerebral blood flow (CBF). A closed circuit re-breathing system was used to deliver the Xe in order to make the treatment efficient and economical. A bolus-tracking method using indocyanine green (ICG) as a flow tracer with time-resolved near-infrared (TR-NIR) technique was used to measure CBF and CMRO2 in newborn piglets.
Hypothermia, in which the brain is cooled to 32-33 °C, has been shown to be neuroprotective for brain injury caused by
hypoxia-ischemia, head trauma, or neonatal asphyxia. Neuroprotective effect of Hypothermia is partly due to
suppression of brain metabolism and cerebral blood flow (CBF). The ability to measure CBF at the bedside provides a
means of detecting, and thereby preventing, secondary ischemia during neuro intensive care before brain injury occurs.
The purpose of the present study is to investigate the ability of a time-resolved near-infrared (TR-NIR) bolus-tracking
method using indocyanine green as an intravascular flow tracer to measure CBF during cooling in a newborn animal
model. For validation, CBF was independently measured by computed tomography (CT) perfusion. The results show a
good agreement between CBF obtained with the two methods (R2 ≈ 0.84, Δ ≈ 5.84 ml. min -1.100 g -1, 32-38.5 °C),
demonstrating the ability of the TR-NIR technique to non-invasively measure absolute CBF in-vivo during dynamic
hypothermia. The TR-NIR technique reveals that CBF decreases from 54.3 ± 5.4 ml. min -1.100 g -1, at normothermia
(Tbrain of 38.5 °C), to 33.8 ± 0.9 ml. min -1.100 g -1 at Tbrain of 32 °C during the hypothermia treatment.
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