Optical coherence tomography for quantitative analyses of cerebral vessel morphology and hemodynamics
MetadataShow full item record
The brain plays a crucial role in life-sustaining activities of human, including consciousness, logical thinking, emotional feeling, memory storage, somatic movement, and communication. As the most complex but least understood organ, brain has attracted rising efforts in science and technology to reveal its functions and mechanisms. However, unlike many other organs, the energy consumption of brain is extremely high, accounting for ~20% of entire metabolism in the living body, well above its weight fraction of ~2% . Moreover, brain has no relevant energy storage capacity, which makes it strongly relies on the continuous supply of oxygen and glucose by cerebral blood flow , as metabolism of glucose is the only source of energy for brain except after prolonged starvation . Therefore, one of the most promising area in brain research is through the cerebral blood supply that fuels the cerebral cell metabolism, i.e. the investigation of the cerebrovascular system. Optical coherence tomography (OCT) based angiography has developed as one of the most powerful and invaluable tool for fast volumetric imaging of cerebral vasculature in vivo –. As one of the earliest proposed OCT angiography techniques, optical microangiography (OMAG) demonstrates high potential in detecting OCT signal variations caused by moving red blood cells down to individual capillaries. To further resolve the quantitative flow information (e.g. the blood flow speed), an OCTA-based velocimetry technique was recently proposed to quantify the capillary blood flow within mouse cerebral cortex , and accordingly analyze the cortical capillary transit parameters . The background knowledge of OCT angiography and OCT velocimetry are introduced in chapter 1 of this thesis. One popular paradigm for understanding the brain energy budget is through neurovascular coupling, which correlates the spatiotemporally varying cerebral blood flow with the metabolic needs evoked by local neuronal activities . Nowadays, neurovascular coupling and associated hemodynamic responses have been one of the hottest topic in neuroscience. Taking advantage of the high spatial and temporal resolutions of the OCT velocimetry technique (introduced in chapter 1), the capillary hemodynamics within mouse cerebral cortex, as a key factor in the cerebral oxygen diffusion –, is thoroughly investigated and discussed in chapter 2. This chapter describes a couple of new findings about the microvasculature and capillary hemodynamics in neurovascular coupling, including the mean capillary transit velocity, temporal fluctuation bandwidth, and variations of such during electrical stimulation, along with a Monte Carlo numerical model to simulate the spatiotemporally-coupled capillary transit parameters, allowing for better understanding of the neurovascular coupling and functional hyperemia. Apart from the capillaries, the penetrating vessels, which bridge the subsurface microvascular bed with the mesh of surface communicating vessels, are usually lack of characterization. Moreover, in contrast to the surface and subsurface vasculatures, the penetrating vessels are highly devoid of anastomoses , , which makes them the anatomical bottleneck in cerebral blood supply , . Clinically, the degeneration and dysfunction of penetrating vessels appear to be direct related to Alzheimer’s disease, cerebral amyloid angiopathy, perceptual deficit, and stroke. In chapter 3, we propose a statistical cerebral penetrating vessel mapping approach that is innovatively redesigned from OCT velocimetry. This method allows for automatic quantification of penetrating arterioles and ascending venules from large volume OCT angiography data, and accordingly contributes to the topological and morphological analyses of cortical vasculature in functioning brains. As the “main street” of the cerebral vascular architecture, the surface communicating vessels play a leading role in the cortical tissue development in both normal and pathological conditions. For instance, the redundancy in cortical surface vessels supports persistent cerebral blood flow , and the anastomosis of surface vessels in stroke further protects cortical tissue from ischemic injury . On the other hand, the functioning of the surface communicating vessels is highly related to their morphological properties, including vessel diameter, vessel torutosity, vessel branching angle et. al. In chapter 4, we present a comprehensive framework for quantitative characterization of the cortical surface vessels, with newly-designed methods for automated vessel diameter measurement and vessel tracing. The proposed algorithmic approach is highly adaptable, and can easily be extended to other imaging modalities, making it of great value in multiple clinical settings. Other than the cerebral blood flow, as a high-sensitive approach to resolve signal variations, dynamic OCT processing may provide subtle information of cortical cell dynamics. In the future, we plan to image and quantify the subcellular motion of neuron cells in the brain in vivo. Some of the preliminary results have been drafted in chapter 6. The successful characterization of cortical cell metabolism and cerebral blood flow with OCT may prove its high potential in future studies of neurovascular coupling.
- Bioengineering