It is well known that neural activity and function is inherently correlated to local availability of oxygen and oxygen consumption for energy in vivo. However, due to limitations in current technologies, tissue oxygenation levels cannot be easily measured at the tissue-implant interface. Current, minimally-invasive techniques to measure tissue oxygenation levels in vivo typically suffer from low spatial and temporal resolution around implant sites. In addition, oxygenation levels are either qualitative, indirect measurements (i.e BOLD fMRI and biophotonic techniques), or are quantitative only at the point of measurement (i.e highly invasive, polarographic methods). Therefore, there is a critical need for a minimally invasive, quantitative measurement of pO2 with high spatiotemporal resolution that can serve as a biomarker for interfacial tissue health under chronic implantation conditions.
In this study, a technique to quantitatively map tissue oxygenation levels in the microenvironment surrounding implanted microprobes is performed using a novel tissue oximetry technique known as proton imaging of siloxanes to map tissue oxygenation levels (PISTOL). A polydimethyl siloxane (PDMSO, ~410 g/mol) contrast agent was embedded in a soft, PDMS based matrix that was coated around a silicone catheter (0.6-1.5 mm diameter) and various MR-compatible microwires such as platinum-iridium (75 µm diameter), tungsten (100 µm diameter), gold (50 µm diameter). Siloxane loaded implants were scanned in phantoms and ex vivo brains in a time-dependent manner using a Bruker 7T preclinical MRI system with either a volume or surface coil at room temperature. A PISTOL scan was conducted after suppression of the water/fat signal using a combination of pulse-burst saturation recovery with frequency-selective excitation of the PDMSO-siloxane resonance. After analysis with custom MATLAB algorithms, pO2 levels were correlated to PDMSO-based siloxane T1 relaxation times where decreasing oxygen tension displays longer relaxation times. With the exception of thick, platinum based electrodes that displayed susceptibility related artifacts, the MR/PISTOL was sensitive enough to spatially map pO2 levels around MR-compatible, microelectrode implants. Selective, spatial mapping of matrix embedded siloxane based sensors showed ambient air levels (~140-150 torr) close the ex vivo brain surface and decreasing pO2 levels along the length of the shank going into the brain. The current spatial resolution of the mapping was ~150-300 µm around the implant based on the chosen field of view (FOV) during the imaging process. Preliminary results from this study demonstrate that PISTOL MR imaging technique can be useful for measuring tissue oxygenation around microscale brain implants. Quantitative tissue oximetry can potentially be used for deep brain imaging in conjunction with brain implants. Current studies are on-going to quantitate pO2 levels in vivo under chronic conditions.