According to the World Health Organization, 31% of worldwide deaths are due to cardiovascular diseases (CVDs). The principal cause of death in 85% of the CVD cases are heart attack and stroke. About 795,000 people have a new or recurrent stroke annually in the U.S.A. alone. A study pointed out that 63% of stroke patients have at least one episode of cerebral hypoxia being able to cause coma, seizures, and even brain death. In previous work, we introduced a biocompatible, mechanically stable, and transparent nanocrystalline yttria-stabilized-zirconia (nc-YSZ) cranial implant to provide optical access to the brain. The nc-YSZ implant may facilitate the diagnosis and treatments of neurological disorders by imaging and laser-based techniques. In this study, we evaluate the scope of diffuse reflectance spectroscopy through the nc-YSZ cranial implant in the diagnosis of oxygen consumption in normal and hypoxic conditions (greater and less than 95%, respectively). We use the Monte Carlo method to assess the optical access provided by the implant to detect normal and decreased oxygen consumption. To emulate the brain tissue, we used a four-layer structure: skull, gray matter with an embedded blood vessel, white matter, and air at the top, structured in a numerical model with anisotropy as well as Rayleigh and Mie scattering. We analyze two scenarios, constant blood volume at variable oxyhemoglobin saturation, and constant oxyhemoglobin saturation at variable blood volume. We use light irradiation sources at 756 and 810 nm to compute light propagation in a semi-infinite medium and diffuse reflectance backward. The penetration depth and diffusely backscattered energy showed the feasibility of monitoring hypoxia episodes while blood flux in vessels decreases during a stroke with more accuracy when the volume of the blood vessel is reduced in a stroke.
Laser-based diagnostics and therapeutics show promise for many neurological disorders. However, the poor transparency of the cranial bone limits the spatial resolution and interaction depth that can be achieved with these technologies. We have recently demonstrated a new method to address this challenge in biomedical research through the use of a novel transparent cranial implant made from nanocrystalline yttria-stabilized zirconia (ncYSZ). In addition, we have also explored the use of optical clearing agents (OCAs) to achieve a local, reversible and temporal reduction of the scalp scattering prior light irradiation. Our results show that the transparent nc-YSZ implants coupled with the OCAs perform well in providing enhanced optical access to the brain tissue, without need for recurrent craniotomies or scalp removal.
Optical brain imaging based on intrinsic signals has revealed new insights into functional brain activation imaging. The main obstacle to this approach is the highly scattering cranial bone over the cortex which hinders the observation of intrinsic optical signals. We have introduced a novel solution for this limitation by proposing a transparent cranial implant providing long-term optical access to the brain, which we call the Window to the Brain (WttB) implant. In this study, we evaluated the feasibility of the WttB implant for multi-wavelength intrinsic optical signal imaging of the brain.
KEYWORDS: Zirconium dioxide, Transparency, In vivo imaging, Transmittance, Ceramics, Temperature metrology, Brain, Skull, Thermography, Diagnostics and therapeutics
Laser-based diagnostics and therapeutics show promise for many neurological disorders. However, the poor transparency of cranial bone limits the spatial resolution and interaction depth that can be achieved. We addressed this limitation previously, by introducing a novel cranial prosthesis made of a transparent nanocrystalline yttria-stabilized zirconia (nc-YSZ) which aims to enhance the diagnosis and treatment of neurological diseases by providing chronic optical access to the brain. By using optical coherence tomography, we have demonstrated the initial feasibility of ncYSZ implants for cortical imaging in an acute murine model. Although zirconia-based implants have been known for their excellent mechanical properties, the in vivo application was found to be affected by long-term failures, due to low temperature degradation. Accelerated aging simulations in humid environments at slightly elevated temperatures and over long periods typically transforms the ceramic surface into a monoclinic structure through a stress-corrosion-type mechanism. It was expected that the new nc-YSZ would show sufficient resistance to humid environments in comparison to the conventional zirconia implant. However, even a modest amount of transformation can change optical characteristics such as transparency. Herein we present the results of a simulated ageing study following the guidelines from the ISO 13356:2008 on aging of surgical zirconia ceramics. Comparison of %monoclinic transformation, optical transparency and mechanical hardness of nc-YSZ samples at baseline and following 25 and 100 h hydrothermal treatments shows our implant can withstand these extended ageing treatments.
The laser speckle flowmetry methods based on laser speckle imaging (LSI) have attracted extensive attention recently because they can image brain blood flow with high spatiotemporal resolution. However, the poor transparency of the cranial bone limits the spatial resolution and the imaging depth. This problem has previously been addressed in animal studies by removing or thinning the skull to transparency. Nevertheless, a permanent and reliable solution has not yet been developed. Our study demonstrates a new method to address this challenge in biomedical imaging research, through the use of novel transparent cranial implants made from nanocrystalline yttria-stabilized zirconia (nc-YSZ). By applying LSI to underlying brain in an acute murine model, we show that spatial resolution and quantitative accuracy of blood flow measurement are improved when imaging through transparent nc-YSZ implants relative to native cranium. As such, these results provide the initial evidence supporting the feasibility of nc-YSZ transparent cranial implant as a clinically-viable long-term optical access for LSI on a chronically-recurring basis, thereby suppressing the need for repeated craniotomies. Successful development of this method has the potential to advance the study of neuropathologies or novel neuro-procedures in animal models where measurement of cerebral blood flow is of interest, such as blood flow changes during stroke, changes in blood flow due to functional activation, and spreading depolarization and its role in brain injuries, pathophysiology of migraine, and subarachnoid hemorrhage.
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