Measurement of Cerebral Circulation in Human

In this chapter, we review state-of-the-art non-invasive techniques to monitor and study cerebral circulation in humans. The measurement methods can be divided into two categories: direct and indirect methods. Direct methods are mostly based on using contrast agents delivered to blood circulation. Clinically used direct methods include single-photon emission computed tomography (SPECT), positron emission tomography (PET), magnetic resonance imaging (MRI) with contrast agents, xenon computed tomography (CT), and arterial spin labeling (ASL) MRI. Indirect techniques are based on measuring physiological parameters reflecting cerebral perfusion. The most commonly used indirect methods are near-infrared spectroscopy (NIRS), transcranial Doppler ultrasound (TCD), and phase-contrast MRI. In recent years, few more techniques have been intensively developed, such as diffuse correlation spectroscopy (DCS) and microwave-based techniques, which are still emerging as methods for cerebral circulation monitoring. In addition, methods combining different modalities are discussed and, as a summary, the presented techniques and their benefits for cerebral circulation will be compared

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

Developing novel fluorescent probe for peroxynitrite: implication for understanding the roles of peroxynitrite and drug discovery in cerebral ischemia reperfusion injury

Session 7 - Oral PresentationsSTUDY GOAL: Peroxynitrite (ONOO‐) is a cytotoxic factor. As its short lifetime, ONOO‐ is hard to be detected in biological systems. This study aims to develop novel probe for detecting ONOO‐ and understand the roles of ONOO‐ in ischemic brains and drug discovery ABSTRACT: MitoPN‐1 was found to be a ONOO‐ specific probe with no toxicity. With MitoPN‐1, we studied the roles of ONOO‐ in hypoxic neuronal cells in vitro and MCAO …postprin

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

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

Cerebral Circulation

Diagnostics and diseases related to the cerebrovascular system are constantly evolving and updating. 3D augmented reality or quantification of cerebral perfusion are becoming important diagnostic tools in daily practice and the role of the cerebral venous system is being constantly revised considering new theories such as that of “the glymphatic system.” This book provides updates on models, diagnosis, and treatment of diseases of the cerebrovascular system

Optical tecnology developments in biomedicine: history, current and future

Biomedical optics is a rapidly emerging field for medical imaging and diagnostics. This paper reviews several biomedical optical technologies that have been developed and translated for either clinical or pre-clinical applications. Specifically, we focus on the following technologies: 1) near-infrared spectroscopy and tomography, 2) optical coherence tomography, 3) fluorescence spectroscopy and imaging, and 4) optical molecular imaging. There representative biomedical applications are also discussed here