Optical Microring Resonators for Photoacoustic Imaging and Detection.

This work is to utilize the superior characteristics of polymer microring resonators in ultrasound detection to push the application of photoacoustic imaging to an entirely new level. We first demonstrated significantly improved imaging quality for photoacoustic tomography (PAT) using microring detectors. For wideband PAT, the microring detectors were able to faithfully detect both the boundaries and the inner structure, while piezoelectric detectors can only preserve one of the two aspects. For high-resolution PAT over a large imaging area, we imaged 50 µm black beads and found that microrings produced high-resolution imaging over a 16-mm-diameter imaging area while the 500 µm piezoelectric detectors only obtained high-resolution imaging over a small area around center. Pure optical photoacoustic microscopy (PAM) has been demonstrated. Microring ultrasonic resonators were applied in in vivo photoacoustic imaging for the first time. Good imaging signal-to-noise ratio and high axial resolution of 8 µm were calibrated. As a comparison, a commercial hydrophone with similar sensitivity produced a low axial resolution of 105 µm. A 5 mm miniaturized probe consisting of a fiber to deliver excitation laser pulses and microring detectors for ultrasound detection has been fabricated for photoacoustic endoscopy. The calibrated high radial resolution of 21 µm was higher than other types of endoscopic photoacoustic probes, around 40 µm or larger. A photoacoustic correlation spectroscopy (PACS) technique was proposed. In a proof-of-concept experiment, we demonstrated low-speed flow measurement of ~15 µm/s by the PACS technique. We also demonstrated in vivo flow speed measurement of red blood cells in capillaries in a chick embryo model by PACS. Other techniques might have difficulties to measure it due to the low signal contrast and/or poor resolutions. We also proposed terahertz electromagnetic pulse detection by photoacoustic method. We used carbon nanotube composites as efficient photoacoustic transmitters and microrings as sensitive detectors. The photoacoustic method provides low-cost and real-time terahertz detection (~µs), which is difficult by conventional terahertz detectors, such as a bolometer or a pyroelectric detector.Ph.D.Electrical EngineeringUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/91497/1/chensll_1.pd

Terahertz Pulse Detection Techniques and Imaging Applications

Recent years have witnessed successful developments of detection techniques of terahertz (THz) pulse radiation and its imaging applications such as security, medicine and environmental sensing, to name an important few. Progress of detection techniques has been made in many aspects, including detection sensitivity, real‐time detection, room‐temperature operation, detection bandwidth and dynamic range, spatial (wavefront) and temporal profiles and so on. New detection techniques utilizing cutting‐edge materials, sensors, systems and even novel detection mechanisms contribute to advances in terahertz pulse detection. While detection techniques continuously improve, terahertz pulsed imaging (TPI) also finds broad and intriguing applications. For instance, TPI has shown applications in nondestructive evaluation in pharmaceutics, biomedical characterization of tissues, medical diagnosis of cancers, identification of explosive hazards and examination of art and archeology. The chapter highlights recent progress of terahertz pulse detection techniques and imaging applications

Miniature probe for dual- modality photoacoustic microscopy and white- light microscopy for image guidance: A prototype toward an endoscope

In this study, a novel photoacoustic microscopy (PAM) probe integrating white- light microscopy (WLM) modality that provides guidance for PAM imaging and complementary information is implemented. One single core of an imaging fiber bundle is employed to deliver a pulsed laser for photoacoustic excitation for PAM mode, which provides high resolution with deep penetration. Meanwhile, for WLM mode, the imaging fiber bundle is used to transmit two- dimensional superficial images. Lateral resolution of 7.2 μm for PAM is achieved. Since miniature components are used, the probe diameter is only 1.7- mm. Imaging of phantom and animals in vivo is conducted to show the imaging capability of the probe. The probe has several advantages by introducing the WLM mode, such as being able to conveniently identify regions of interest and align the focus for PAM mode. The prototype of an endoscope shows potential to facilitate clinical photoacoustic endoscopic applications.Integrated photoacoustic microscopy (PAM) and white- light microscopy into a miniature probe can be useful for medical imaging applications such as image guidance for PAM and endoscopy. Further, the two modalities provide complementary information. However, implementation of the probe with miniature size and high resolution has been technically challenging. The novel design of using an imaging fiber bundle and a gradient- index lens offers a simple approach to realize such a miniature probe.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154918/1/jbio201960200.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154918/2/jbio201960200_am.pd

Miniature probe for allâ optical double gradientâ index lenses photoacoustic microscopy

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/146638/1/jbio201800147.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/146638/2/jbio201800147_am.pd

All-optical photoacoustic microscopy

AbstractThree-dimensional photoacoustic microscopy (PAM) has gained considerable attention within the biomedical imaging community during the past decade. Detecting laser-induced photoacoustic waves by optical sensing techniques facilitates the idea of all-optical PAM (AOPAM), which is of particular interest as it provides unique advantages for achieving high spatial resolution using miniaturized embodiments of the imaging system. The review presents the technology aspects of optical-sensing techniques for ultrasound detection, such as those based on optical resonators, as well as system developments of all-optical photoacoustic systems including PAM, photoacoustic endoscopy, and multi-modality microscopy. The progress of different AOPAM systems and their representative applications are summarized

Photoacoustic microscopy for evaluating a lipopolysaccharideâ induced inflammation model in mice

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/148356/1/jbio201800251_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/148356/2/jbio201800251.pd

Inhibition of Serine Protease Activity Protects Against High Fat Diet-Induced Inflammation and Insulin Resistance.

Recent evidence suggests that enhanced protease-mediated inflammation may promote insulin resistance and result in diabetes. This study tested the hypothesis that serine protease plays a pivotal role in type 2 diabetes, and inhibition of serine protease activity prevents hyperglycemia in diabetic animals by modulating insulin signaling pathway. We conducted a single-center, cross-sectional study with 30 healthy controls and 57 patients with type 2 diabetes to compare plasma protease activities and inflammation marker between groups. Correlations of plasma total and serine protease activities with variables were calculated. In an in-vivo study, LDLR-/- mice were divided into normal chow diet, high-fat diet (HFD), and HFD with selective serine protease inhibition groups to examine the differences of obesity, blood glucose level, insulin resistance and serine protease activity among groups. Compared with controls, diabetic patients had significantly increased plasma total protease, serine protease activities, and also elevated inflammatory cytokines. Plasma serine protease activity was positively correlated with body mass index, hemoglobin A1c, homeostasis model assessment-insulin resistance index (HOMA-IR), tumor necrosis factor-α, and negatively with adiponectin concentration. In the animal study, administration of HFD progressively increased body weight, fasting glucose level, HOMA-IR, and upregulated serine protease activity. Furthermore, in-vivo serine protease inhibition significantly suppressed systemic inflammation, reduced fasting glucose level, and improved insulin resistance, and these effects probably mediated by modulating insulin receptor and cytokine expression in visceral adipose tissue. Our findings support the serine protease may play an important role in type 2 diabetes and suggest a rationale for a therapeutic strategy targeting serine protease for clinical prevention of type 2 diabetes