Neurological injury is a devastating complication that can occur during surgical procedures under general anesthesia, particularly for surgeries requiring cardiopulmonary bypass and carotid clamping. Although standard monitors of the cardiovascular and respiratory systems have been used for decades during anesthesia, there is no standard monitor to directly assess cerebral perfusion. This indicates an alarming gap in the management of patients, particularly given that the central nervous system is often the primary target for anesthetics and analgesics, and both anesthesia and surgical procedures can impair cerebral oxygen delivery to the brain. Instead, arterial blood pressure (ABP) is monitored and maintained within normal limits with the assumption that cerebral autoregulation maintains adequate perfusion over a large range of cerebral perfusion pressures. However, anesthesia or surgery or pre-existing conditions can impair autoregulation such that typically occurring drops in ABP during anesthesia can lead to cerebral hypoperfusion and ischemia. Notably, this intraoperative hypotension has been linked to a higher incidence of postoperative stroke and cognitive impairment. To address this urgent need for a neuromonitoring tool, we propose to utilize a near-infrared optical system that integrates frequency domain (FD) near infrared spectroscopy (NIRS) measurements of hemoglobin oxygenation (SO2) with diffuse correlation spectroscopy (DCS) measurements of cerebral blood flow (CBF), and will provide a robust measure of cerebral oxygen delivery and consumption (CMRO2). Building on more than twenty years of experience developing NIRS instruments, algorithms and applications, we propose to apply innovative strategies made available by the combination of these two optical modalities to overcome limitations inherent to each individually, and to provide more accurate estimates of SO2, CBF and CMRO2 than currently available. Specifically in Aim 1 we will optimize novel algorithms that exploit multi- distance and multi-wavelength measurements of our recently integrated FD-NIRS / DCS instrument, as well as hemoglobin fluctuations to better quantify and distinguish cerebral from extracerebral parameters, and reduce errors due to water and scattering assumptions.
In Aim 2 we will assess precision and accuracy of our measurements of SO2, CBF and CMRO2, in tissue-like phantoms.
In Aim 3 we will validate repeatability, precision and accuracy of the optical measurements in healthy human subjects with a series of manipulations and validation studies against MRI, and perform a clinical feasibility study including patients undergoing surgeries requiring carotid endarterectomy (CEA). These pilot clinical measurements will demonstrate the potential of the novel device in providing a prompt indicator of compromised oxygen delivery and consumption and predicting which CEA patients will go on and develop early cognitive dysfunction. The successful development and demonstration of our proposed technology will ultimately lead to new patient management approaches for reducing perioperative neurological injury, protecting neurocognitive function, and reducing the overall morbidity and mortality associated with general anesthesia in general and carotid endarterectomy in particular.
There is a great need for a neuromonitoring tool to provide a robust measure of cerebral oxygen delivery and consumption during surgical procedures under general anesthesia. We propose to utilize a combined near infrared spectroscopy (NIRS) and diffuse correlation spectroscopy (DCS) device and to develop novel algorithms to optimize quantitative monitoring of cerebral blood flow and oxygen consumption. The successful development, validation and clinical feasibility demonstration of our proposed technology will ultimately lead to new patient management approaches for reducing perioperative neurological injury, protecting neurocognitive function, and reducing the overall morbidity and mortality associated with general anesthesia in general, and in particular patients undergoing carotid endarterectomy.
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