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Developing the Next-generation Biomedical Optical Systems: Higher Sensitivity, Deeper in Tissue, and Faster Dynamics.
- Tordera Mora, Jorge
- Advisor(s): Gao, Liang
Abstract
This dissertation proposes several solutions to alleviate two of the most fundamental problems in biomedical optics: imaging deep in tissue via photoacoustic imaging (PAI) and capturing fast dynamics through light field tomography (LIFT). On the one hand, photoacoustic tomography can image with chemical specificity up to tens of centimeters in tissue. However, its applicability is still limited due to its relatively poor sensitivity and noise robustness, high cost, and setup bulkiness. In order to overcome such limitations, I present three novel techniques: Photoacoustic Shadow-Casting Microscopy (PASM), All-optical Photoacoustic Microscopy (AOPAM), and Generalized Spatial Coherence (GSC). First, PASM is a technique that detects biological samples with unprecedented sensitivity by using an optical absorber that acts as a photoacoustic signal amplifier alleviating photothermal damage in tissue samples while enabling fast acquisition and time-lapse applications. Secondly, AOPAM eliminates the use of conventional piezoelectric transducers in PAI setups by introducing an optical resonating ultrasound sensor: a Fabry-Perot etalon. This configuration allows system miniaturization and expands PAI’s applicability to intravascular imaging of atherosclerotic plaques and brain imaging in freely behaving rodents. Thirdly, GSC is a PAI beamforming reconstruction algorithm that takes advantage of spatial coherence between signals from multiple transducers to output state-of-the-art imaging quality metrics and noise robustness compared to gold standard techniques, such as delay-and-sum and similar spatial coherence beamforming techniques such as filtered delay-multiply-and-sum and short-lag spatial coherence. On the other hand, LIFT is a novel imaging method that allows single snapshot capturing of three-dimensional scenes at ultrafast speeds. In a nutshell, LIFT compresses three-dimensional scenes to one-dimensional detectors in order to enhance acquisition speed by adequately rotating an array of cylindrical lenslets thus reformulating optical imaging as a computed tomography problem. LIFT has depth refocusing and extended depth-of-field capabilities as opposed to classical optical microscopy. In this work, LIFT’s application is three-dimensional fluorescent microscopy at kilohertz rates of neuronal action potentials, microfluidic flow sculpting dynamics, and cardiovascular voltage waves.
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