On The Development of a Dynamic Contrast-Enhanced Near-Infrared Technique to Measure Cerebral Blood Flow in the Neurocritical Care Unit

A dynamic contrast-enhanced (DCE) near-infrared (NIR) method to measure cerebral blood flow (CBF) in the neurocritical care unit (NCU) is described. A primary concern in managing patients with acquired brain injury (ABI) is onset of delayed ischemic injury (DII) caused by complications during the days to weeks following the initial insult, resulting in reduced CBF and impaired oxygen delivery. The development of a safe, portable, and quantitative DCE-NIR method for measuring CBF in NCU patients is addressed by focusing on four main areas: designing a clinically compatible instrument, developing an appropriate analytical framework, creating a relevant ABI animal model, and validating the method against CT perfusion. In Chapter 2, depth-resolved continuous-wave NIR recovered values of CBF in a juvenile pig show strong correlation with CT perfusion CBF during mild ischemia and hyperemia (r=0.84, p\u3c0.001). In particular, subject-specific light propagation modeling reduces the variability caused by extracerebral layer contamination. In Chapter 3, time-resolved (TR) NIR improves the signal sensitivity to brain tissue, and a relative CBF index is be both sensitive and specific to flow changes in the brain. In particular, when compared with the change in CBF measured with CT perfusion during hypocapnia, the deconvolution-based index has an error of 0.8%, compared to 21.8% with the time-to-peak method. To enable measurement of absolute CBF, a method for characterizing the AIF is described in Chapter 4, and the theoretical basis for an advanced analytical framework—the kinetic deconvolution optical reconstruction (KDOR)—is provided in Chapter 5. Finally, a multichannel TR-NIR system is combined with KDOR to quantify CBF in an adult pig model of ischemia (Chapter 6). In this final study, measurements of CBF obtained with the DCE-NIR technique show strong agreement with CT perfusion measurements of CBF in mild and moderate ischemia (r=0.86, p\u3c0.001). The principle conclusion of this thesis is that the DCE-NIR method, combining multidistance TR instrumentation with the KDOR analytical framework, can recover CBF values that are in strong agreement with CT perfusion values of CBF. Ultimately, bedside CBF measurements could improve clinical management of ABI by detecting delayed ischemia before permanent brain damage occurs

Digging Deeper with Diffuse Correlation Spectroscopy

Patients with neurological diseases are vulnerable to cerebral ischemia, which can lead to brain injury. In the intensive care unit (ICU), neuromonitoring techniques that can detect flow reductions would enable timely administration of therapies aimed at restoring adequate cerebral perfusion, thereby avoiding damage to the brain. However, suitable bedside neuromonitoring methods sensitive to changes of blood flow and/or oxygen metabolism have yet to be established. Near-infrared spectroscopy (NIRS) is a promising technique capable of non-invasively monitoring flow and oxygenation. Specifically, diffuse correlation spectroscopy (DCS) and time-resolved (TR) NIRS can be used to monitor blood flow and tissue oxygenation, respectively, and combined to measuring oxidative metabolism. The work presented in this thesis focused on advancing a DCS/TR-NIRS hybrid system for acquiring these physiological measurements at the bedside. The application of NIRS for neuromonitoring is favourable in the neonatal ICU since the relatively thin scalp and skull of infants has minimal effect on the detected optical signal. Considering this application, the validation of a combined DCS/NIRS method for measuring the cerebral metabolic rate of oxygen (CMRO2) was investigated in Chapter 2. Although perfusion changes measured by DCS have been confirmed by various flow modalities, characterization of photon scattering in the brain is not clearly understood. Chapter 3 presents the first DCS study conducted directly on exposed cortex to confirm that the Brownian motion model is the best flow model for characterizing the DCS signal. Furthermore, a primary limitation of DCS is signal contamination from extracerebral tissues in the adult head, causing CBF to be underestimated. In Chapter 4, a multi-layered model was implemented to separate signal contributions from scalp and brain; derived CBF changes were compared to computed tomography perfusion. Overall, this thesis advances DCS techniques by (i) quantifying cerebral oxygen metabolism, (ii) confirming the more appropriate flow model for analyzing DCS data and (iii) demonstrating the ability of DCS to measure CBF accurately despite the presence of a thick (1-cm) extracerebral layer. Ultimately, the work completed in this thesis should help with the development of a hybrid DCS/NIRS system suitable for monitoring cerebral hemodynamics and energy metabolism in critical-ill patients

Investigation of fontanelle photoplethysmographs and oxygen saturations in intensive care neonates and infants utilising miniature photometric sensors

In children and newborn babies on intensive care, information regarding blood oxygen saturation (SpO2) is determined non-invasively by a device called a pulse oximeter. Sensors are usually placed on a hand or foot where their operation relies on the presence of pulsatile arterial blood. Light shines at two or more wavelengths (usually red and infrared) into the tissue where the pulsatile blood modulates, absorbs and scatters the different wavelengths of light in varying amounts and is detected by a photo-detector as a photoplethysmograph (PPG). The spectral information received is then processed electronically and digitally to determine the amount of haemoglobin present. In the sickest of children blood supply can become compromised to these sensor locations and the pulsatile component of the blood may diminish and pulse oximeter readings may become unreliable, especially at times when accurate blood oxygen information would be vital. Currently the alternative is to take blood from an arterial line and run a relatively lengthy analysis (pulse oximeters are near-instantaneous in their operation) that may be unnecessary if the pulse oximeter could be relied upon at these critical moments. In the smallest of babies invasive sampling of blood becomes even more of an issue as any blood loss could lead to hypovolaemia and introduce extra sites of infection plus it causes a lot of stress to the neonate. Since central blood flow may be preferentially preserved, the anterior fontanelle was investigated as an alternative monitoring site. Custom reflectance fontanelle and reference PPG sensors have been designed and built to investigate the fontanelle in those children at risk of peripheral supply compromise. Dedicated instrumentation and software has also been successfully developed for the control of the sensor electronics and the data-logging of PPG signals for retrospective analysis. Sixteen neonates were recruited for fontanelle monitoring; all were ASA 1 – 3 (ASA ranges from 1 to 5 where 1 is the least sick and 5 is the most critically ill). As part of the approved protocol the delivered oxygen to the patients was artificially altered to look for corresponding changes in PPG signal amplitudes. Amplitude results reveal strong correlations (R > 0.5) between the reference sensor (placed on the foot) and the fontanelle sensor. This suggests that the fontanelle sensor is sensitive to changes in amplitude when oxygen in the blood alters. Correlation of the health of the child, using the ASA score, and the difference in amplitudes of PPGs between the sensors reveals that the fontanelle sensor does detect increasing fontanelle PPG amplitudes when compared to the PPGs from the reference sensor the sicker the child is, confirming that pulsatile flow is being preferentially preserved at the fontanelle in those children who are the most at risk from peripheral supply compromise. SpO2 estimation at the fontanelle reveals a mean difference of 2.2 % to the SpO2 as read by the commercial device and a 1.7 % difference to the blood gas results. These results confirm that the anterior fontanelle may be used as an alternative location for SpO2 measurement in those who are at most risk of peripheral supply compromise

Investigation of fontanelle photoplethysmographs and oxygen saturations in intensive care neonates and infants utilising miniature photometric sensors

In children and newborn babies on intensive care, information regarding blood oxygen saturation (SpO2) is determined non-invasively by a device called a pulse oximeter. Sensors are usually placed on a hand or foot where their operation relies on the presence of pulsatile arterial blood. Light shines at two or more wavelengths (usually red and infrared) into the tissue where the pulsatile blood modulates, absorbs and scatters the different wavelengths of light in varying amounts and is detected by a photo-detector as a photoplethysmograph (PPG). The spectral information received is then processed electronically and digitally to determine the amount of haemoglobin present. In the sickest of children blood supply can become compromised to these sensor locations and the pulsatile component of the blood may diminish and pulse oximeter readings may become unreliable, especially at times when accurate blood oxygen information would be vital. Currently the alternative is to take blood from an arterial line and run a relatively lengthy analysis (pulse oximeters are near-instantaneous in their operation) that may be unnecessary if the pulse oximeter could be relied upon at these critical moments. In the smallest of babies invasive sampling of blood becomes even more of an issue as any blood loss could lead to hypovolaemia and introduce extra sites of infection plus it causes a lot of stress to the neonate. Since central blood flow may be preferentially preserved, the anterior fontanelle was investigated as an alternative monitoring site. Custom reflectance fontanelle and reference PPG sensors have been designed and built to investigate the fontanelle in those children at risk of peripheral supply compromise. Dedicated instrumentation and software has also been successfully developed for the control of the sensor electronics and the data-logging of PPG signals for retrospective analysis. Sixteen neonates were recruited for fontanelle monitoring; all were ASA 1 – 3 (ASA ranges from 1 to 5 where 1 is the least sick and 5 is the most critically ill). As part of the approved protocol the delivered oxygen to the patients was artificially altered to look for corresponding changes in PPG signal amplitudes. Amplitude results reveal strong correlations (R > 0.5) between the reference sensor (placed on the foot) and the fontanelle sensor. This suggests that the fontanelle sensor is sensitive to changes in amplitude when oxygen in the blood alters. Correlation of the health of the child, using the ASA score, and the difference in amplitudes of PPGs between the sensors reveals that the fontanelle sensor does detect increasing fontanelle PPG amplitudes when compared to the PPGs from the reference sensor the sicker the child is, confirming that pulsatile flow is being preferentially preserved at the fontanelle in those children who are the most at risk from peripheral supply compromise. SpO2 estimation at the fontanelle reveals a mean difference of 2.2 % to the SpO2 as read by the commercial device and a 1.7 % difference to the blood gas results. These results confirm that the anterior fontanelle may be used as an alternative location for SpO2 measurement in those who are at most risk of peripheral supply compromise.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

44th Rocky Mountain Conference on Analytical Chemistry

Final program, abstracts, and information about the 44th annual meeting of the Rocky Mountain Conference on Analytical Chemistry, co-endorsed by the Colorado Section of the American Chemical Society and the Society for Applied Spectroscopy. Held in Denver, Colorado, July 28 - August 1, 2002

Brain Injury

The present two volume book "Brain Injury" is distinctive in its presentation and includes a wealth of updated information on many aspects in the field of brain injury. The Book is devoted to the pathogenesis of brain injury, concepts in cerebral blood flow and metabolism, investigative approaches and monitoring of brain injured, different protective mechanisms and recovery and management approach to these individuals, functional and endocrine aspects of brain injuries, approaches to rehabilitation of brain injured and preventive aspects of traumatic brain injuries. The collective contribution from experts in brain injury research area would be successfully conveyed to the readers and readers will find this book to be a valuable guide to further develop their understanding about brain injury

Instrumentation and calibration protocol for a continuous wave near infrared hemoximeter

Quantification of hemoglobin content in vivo using continuous wave (CW) near infrared spectroscopy requires an accurate calibration of the measuring system. The authors introduce a recently developed instrument and focus their attention on the calibration issue, proposing a calibration procedure specifically designed for their system, but which can be easily generalized for other CW near-infrared systems. In the paper, the most important calibration procedures and the results obtained are discussed in detail