Non-Invasive Multimodal High-Resolution Optical Acoustic Imager for Early Hypoxia Detection in Neonatal Brain

Abstract

In preterm infants, the brain is the most vulnerable organ. Cerebral ischemia induces severe brain lesions that lead to neurodevelopmental impairments. Monitoring the brain’s oxygenation enables an early diagnosis and will thus help to treat ischemia. For this purpose, a non-invasive multimodal high-resolution imager is developed. This imaging system combines the advantages of two complementary imaging techniques, near-infrared optical tomography (NIROT) and optoacoustic imaging (OAI). OAI features the high spatial resolution of ultrasound imaging as well as the high contrast of optical imaging of vessels. The OAI signal is, however, spectrally distorted due to the unknown fluence distribution within the tissue. Fluence calculation based on NIROT reconstructions of the optical properties enable a correction of the OAI signal. Additionally, NIROT enables the monitoring of the tissue oxygenation of background tissue. The multimodal imager is developed in a collaborative effort between the Biomedical Optics Research Laboratory (BORL) in Zurich and the Institute of Applied Physics in Berne. This thesis presents the research and development of the NIROT part. Four studies are presented. First, the robustness of the image reconstruction to perturbations in source/detector location was examined. This was performed analytically and numerically for homogeneous phantoms and numerically for inhomogeneous phantoms. Numerical simulations were based on the NIROT software, Nirfast. The simulations yielded that reconstructed optical properties are highly sensitive to errors in source/detector location for one source-detector pair. However, small errors in the source/detector locations tend to cancel each other for more than one source-detector pair. Second, the successful development and design of the NIROT imager is presented. The NIROT sensor features highly flexible microfiber bundles as light guides. 3D printing technology was applied for inner sensor parts and to create a mold for silicone casting. Biocompatible 2-component silicone is casted to form a soft curved sensor shell that adapts to the surface structure. At the same time, it prevents light from directly travelling from a source fiber to the detector. Silicone phantoms were produced to perform a thorough phantom validation of the sensor prototype. Third, silicone dyes were characterized in terms of their optical properties to create phantoms with wavelength dependent optical properties. This enables a stable verification and validation method of NIRS/NIROT devices. These three studies lead up to the fourth study: A first laboratory experiment combining the full multimodal system, which was then used in a phantom study. Finally, it is found that NIROT serves to correct spectrally distorted OA signals, likewise OA and Ultrasound images could be used to provide NIROT reconstructions with priors. Overall, we reinforced the notion that this hybrid modality has great potential for clinical application, i.e. the early detection of cerebral ischemia in preterm infants.