Analysis of slow wave oscillations in cerebral haemodynamics and metabolism following subarachnoid haemorrhage.

Aneurysmal subarachnoid haemorrhage (SAH) causes the greatest loss of productive life years of any form of stroke. Emerging concepts of pathophysiology highlight early abnormalities of microvascular function, including impaired autoregulation of cerebral blood flow and flow-metabolism coupling, as key causes of cerebral ischaemia and poor outcome. Near infrared spectroscopy (NIRS) is a non-invasive optical technique which may help identify cerebral microvascular dysfunction. The aim of this research is to investigate the status of flow-metabolism coupling by examining phase relationships between NIRS-derived concentrations of oxy-haemoglobin ([HbO2]), deoxy-haemoglobin ([HHb]) and cytochrome c oxidase oxidation ([oxCCO]). Eight sedated ventilated patients with SAH were investigated. A combined NIRS broadband and frequency domain spectroscopy system was used to measure [HbO2], [HHb] and [oxCCO] alongside other multimodal neuromonitoring. Wavelet analysis of phase relationships revealed antiphase [HbO2]-[oxCCO] and in-phase [HbO2]-[HHb] oscillations between 0.1Hz-0.01Hz consistent with compromised flow-metabolism coupling. NIRS derived variables might offer unique insights into microvascular and metabolic dysfunction following SAH, and in the future identify therapeutic windows or targets

Hyperspectral imaging solutions for brain tissue metabolic and hemodynamic monitoring: past, current and future developments

Hyperspectral imaging (HSI) technologies have been used extensively in medical research, targeting various biological phenomena and multiple tissue types. Their high spectral resolution over a wide range of wavelengths enables acquisition of spatial information corresponding to different light-interacting biological compounds. This review focuses on the application of HSI to monitor brain tissue metabolism and hemodynamics in life sciences. Different approaches involving HSI have been investigated to assess and quantify cerebral activity, mainly focusing on: (1) mapping tissue oxygen delivery through measurement of changes in oxygenated (HbO₂) and deoxygenated (HHb) hemoglobin; and (2) the assessment of the cerebral metabolic rate of oxygen (CMRO₂) to estimate oxygen consumption by brain tissue. Finally, we introduce future perspectives of HSI of brain metabolism, including its potential use for imaging optical signals from molecules directly involved in cellular energy production. HSI solutions can provide remarkable insight in understanding cerebral tissue metabolism and oxygenation, aiding investigation on brain tissue physiological processes

A multimodal investigation of retrosplenial function

The retrosplenial cortex (RSC) has attracted much attention due to its proposed role in learning and memory. It forms a part of the Papez circuit and is connected with the anterior thalamic nuclei, the hippocampal formation and sensory areas including the visual cortex. Damage to the RSC impairs episodic and spatial memory. Furthermore, dementias such as Alzheimer's Disease have been shown to involve retrosplenial pathology, highlighting the need to better understand the role of this region. The current work explores the contributions of the RSC to visual and spatial processing as well as its vulnerability in a model of amnesia. It is demonstrated here that visual stimulation of anaesthetised mice elicits intrinsic signal responses in the RSC, similar to those seen in the primary visual cortex. Further, it is shown that training on a spatial memory task is paralleled by the gradual formation of a context-specific retrosplenial memory engram, which re-activates upon re-exposure to the task weeks from initial acquisition. Moreover, the overall level of retrosplenial activity and the stability of the engram show a link to the successful expression of spatial memory upon re-exposure to the task. Finally, it is revealed that the disconnection of the mammillary bodies from the anterior thalamus, which is a common feature of diencephalic amnesia, leads to the reduction of the metabolic marker, cytochrome oxidase, in the RSC as well as to widespread microstructural changes revealed by diffusion tensor imaging. Taken together, it is demonstrated here that the RSC is an important integratory hub contributing to the formation of episodic memory and aspects of visual processing and that it displays high sensitivity to the loss of its inputs, which may explain its involvement in a variety of conditions

Hyperspectral imaging of the haemodynamic and metabolic states of the exposed cortex

A hyperspectral imaging (HSI) system to measure and quantify in vivo haemodynamic and metabolic signals from the exposed cerebral cortex of small animals was designed, developed and investigated in this thesis. Imaging brain tissue at multiple narrow wavelength bands in the visible and near-infrared (NIR) range allows one not only to monitor cerebral oxygenation and haemodynamics via mapping of haemoglobin concentration changes, but also to directly target the spatial quantification of cerebral metabolic activity via measurement of the redox states of mitochondrial cytochrome-c-oxidase (CCO). Having both these sets of information in vivo at high resolution on the exposed cortex can provide impactful insight on brain physiology and can help validate corresponding data acquired non-invasively using broadband near-infrared spectroscopy (bNIRS). Several designs and HSI configurations were assessed and compared, including different customised benchtop setups. In the end, a bespoke spectral-scanning HSI system called hNIR, using a supercontinuum laser coupled with a rotating Pellin-Broca prism and a scientific complementary metal-oxide semiconductor (sCMOS) camera, was built, characterised and validated on liquid optical phantoms. In addition, an in-house Monte Carlo (MC) framework for simulating HSI of the haemodynamic and metabolic states of the exposed cortex was also developed using an open-source MC code package (Mesh-based Monte Carlo) and integrated with hNIR, for aiding image reconstruction and enhance quantification, as well as to run computational investigations on the performances of HSI for brain haemodynamic and metabolic monitoring. hNIR was finally applied in vivo on the exposed cerebral cortex of three mice during different levels of hyperoxic and hypoxic stimulation, demonstrating its capability to retrieve high resolution and accurate maps of the relative changes in the concentrations of oxyhaemoglobin (HbO₂), deoxyhaemoglobin (HHb) and the oxidative state of CCO (oxCCO)