Providing molecular fingerprint information, vibrational spectroscopy is a powerful tool for chemical analysis. In the mid-infrared window, FT-IR spectroscopy and microscopy have been routinely used for sample characterization. In the near-IR window, near-infrared spectroscopy has been widely used for tissue analysis and for the detection of lipids in the arterial walls. Yet, these traditional linear spectroscopies have intrinsic limitations. FT-IR spectroscopy suffers from a poor spatial resolution and strong water absorption for the study of living systems. Near-infrared spectroscopy avoids water absorption, yet it suffers from a poor, millimeter-scale spatial resolution in tissue analysis. My thesis focuses on breaking these limitations through photoacoustic and photothermal detection approaches.
The first part of my thesis is on improving the spatial resolution in catheter-based intravascular photoacoustic (IVPA) imaging. By near-infrared excitation of lipids and acoustic detection, IVPA allows depth-resolved identification of lipid-laden atherosclerotic plaque. Thus far, most IVPA endoscopes use multimode fibers, which do not allow tight focusing of photons. Recent experiments on pulse propagation in multimode graded-index fibers have shown a nonlinear improvement in beam quality. Here, we harness this nonlinear phenomenon for the fiber-delivery of nanosecond laser pulses. We built a photoacoustic catheter 1.4 mm outer diameter, offering a lateral resolution as fine as 30 μm within a depth range of 2.5 mm. Such resolution is one order of magnitude better than current multi-mode fiber-based intravascular photoacoustic catheters. At the same time, the delivered pulse energy can reach as high as 20 μJ, which is two orders of magnitude higher than that of an optical resolution photoacoustic endoscope built with single-mode fiber. These improvements are expected to promote the biomedical application of photoacoustic endoscopes which require both high resolution and high pulse energy. Based on the technical advances, my thesis work further demonstrated longitudinal imaging of the same plaque in the same living animal.
Recently developed mid-infrared photothermal (MIP) microscopy overcomes the limitations in FT-IR microscopy by probing the IR absorption-induced photothermal effect using visible light. MIP microscopy yields sub-micrometer spatial resolution with high spectral fidelity and much-reduced water background. The second part of my thesis work pushes the physical limits of MIP microscopy in aspects of detection sensitivity and imaging speed using two approaches. First, taking advantage of the interference scattering effect, the scattering signal from the sample can be greatly enhanced. Together with the relatively large infrared absorption coefficient, the sensitivity of the infrared spectrum is greatly improved, and single virus detection is achieved. Second, by using fluorescence as a thermo-sensitive probe, the temperature raise by infrared absorption can be retrieved in a more efficient way and much higher imaging speed and sensitivity are thus accomplished.
| Identifer | oai:union.ndltd.org:bu.edu/oai:open.bu.edu:2144/44831 |
| Date | 05 July 2022 |
| Creators | Zhang, Yi |
| Contributors | Cheng, Ji-xin |
| Source Sets | Boston University |
| Language | en_US |
| Detected Language | English |
| Type | Thesis/Dissertation |
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