Date of Award
Doctor of Philosophy (PhD)
Photoacoustic tomography (PAT) is a highly promising imaging technology which forms images by detecting the induced pressure waves resulting from pulsed light absorption in biological tissues. Because the excitation source is light, PAT is a very safe, non-ionizing, and non-carcinogenic imaging technology. In biomedicine, PAT has the unique advantage of probing endogenous optical absorbers at different length scales with 100% relative sensitivity. With such scalability, PAT can image anatomical, functional, metabolic, molecular, and genetic contrasts of vasculature, hemodynamics, oxygen metabolism, biomarkers, and gene expression. Among several implementations of PAT, optical-resolution photoacoustic microscopy (OR-PAM) and photoacoustic computed tomography (PACT) are two of the most widely used. OR-PAM can achieve optical diffraction limited spatial resolution with maximum imaging depths up to one transport mean free path (~1 mm in biological tissue). PACT can achieve several centimeters imaging depth in tissue by employing ultrasonic array detectors and inverse algorithms. This dissertation aims to improve the functionality of OR-PAM using a high-frequency linear ultrasonic array, and to advance the performance of linear-array PACT to full view angle capability and higher resolution.
The first part of this dissertation describes the technological advancement of multifocal optical-resolution photoacoustic microscopy (MFOR-PAM). Compared with single-focus OR-PAM, 1D multifocal OR-PAM utilizes both multifocal optical illumination and an ultrasonic transducer array, significantly increasing the imaging speed. We present a reflection-mode 1D multifocal OR-PAM system based on a 1D microlens array that provides multiple foci as well as an ultrasonic transducer array that receives the excited photoacoustic waves from all foci simultaneously. Using a customized microprism to reflect the incident laser beam to the microlens array, the multiple optical foci are aligned confocally with the focal zone of the ultrasonic transducer array. Experiments show the reflection-mode 1D multifocal OR-PAM is capable of imaging microvessels in vivo, and it can image a 6 × 5 × 2.5 mm3 volume at 16 μm lateral resolution in ∼2.5 min, limited by the signal multiplexing ratio and laser pulse repetition rate. While 1D-MFOR-PAM accelerates the scan in only one direction, a two-dimensional MFOR-PAM (2D-MFOR-PAM) fully explores the advantage of a 2D microlens array. By scanning a small range of 250 mm × 250 mm, we eventually obtained a large field of view of 10 mm × 10 mm in ~50 seconds, with a spatial resolution of 15.2 mm.
The second part of this dissertation describes methods of increasing the view angle of linear-array PACT, which suffers from a limited view. While rotating either the transducer array or the imaging objects circularly enables full-view linear-array PACT, this process is time consuming. Here we propose two innovative methods to increase the view angle. The first method is to triple the detection view angle by using two planar acoustic reflectors placed at 120 degrees to each other. Without sacrificing the imaging speed, we form two virtual linear transducer arrays, adding two vantage points. Experimental results show the detection view angle of the linear-array PACT was increased from 80 to 240 degrees. The second method is an ultrasonic thermal encoding approach that is universally applicable to achieve full-view imaging with linear-array PACT. We demonstrate full-view in vivo vascular imaging and compare it to the original linear-array PACT images, showing dramatically enhanced imaging of arbitrarily oriented blood vessels.
The last part of the dissertation describes the development of algorithms for linear-array PACT. The first proposed algorithm is a multi-view Hilbert transformation, which provides accurate optical absorption for full-view linear-array PACT. A multi-view high-frequency PACT imaging system was implemented with a commercial 40-MHz central frequency linear transducer array. By rotating the object through multiple angles with respect to the linear transducer array, we acquired full-view photoacoustic pressure measurements. The in-plane spatial resolution of this full-view linear-array PACT was quantified to be isotropically 60 mm within a 10×10 mm2 field of view. The system was demonstrated by imaging both a leaf skeleton and a zebrafish in vivo. The second algorithm is an inverse linear Radon transformation (ILRT), which allows linear-PACT to achieve isotropic resolution at all depth planes. Images of microspheres acquired by inverse linear Radon transformation PACT (ILRT-PACT) demonstrate that our technique improves the elevational resolution by up to 9.4 times over that of a single linear scan. The technique is further demonstrated through in vivo imaging of the mouse brain through an intact scalp.
Lihong V Wang
Mark A Anastasio, Philip Bayly, Guy Genin, Spencer Lake, David Peters