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Multi-Contrast Photoacoustic Computed Tomography

Citation

Li, Lei (2019) Multi-Contrast Photoacoustic Computed Tomography. Dissertation (Ph.D.), California Institute of Technology. doi:10.7907/FYGX-7M29. https://resolver.caltech.edu/CaltechTHESIS:05072019-120355881

Abstract

Imaging of small animals has played an indispensable role in preclinical research by providing high dimensional physiological, pathological, and phenotypic insights with clinical relevance. Yet pure optical imaging suffers from either shallow penetration (up to ~1–2 mm) or a poor depth-to-resolution ratio (~3), and non-optical techniques for whole-body imaging of small animals lack either spatiotemporal resolution or functional contrast. A stand-alone single-impulse photoacoustic computed tomography (PACT) system has been built, which successfully mitigates these limitations by integrating high spatiotemporal resolution, deep penetration, and full-view fidelity, as well as anatomical, dynamical, and functional contrasts. Based on hemoglobin absorption contrast, the whole-body dynamics and large scale brain functions of rodents have been imaged in real time. The absorption contrast between cytochrome and lipid has enabled PACT to resolve MRI-like whole brain structures. Taking advantage of the distinct absorption signature of melanin, unlabeled circulating melanoma cells have been tracked in real time in vivo.

Assisted by near-infrared dyes, the perfusion processes have been visualized in rodents. By localizing single-dyed droplets, the spatial resolution of PACT has been improved by six-fold in vivo. The migration of metallic-based microrobots toward the targeted regions in the intestines has been monitored in real time. Genetically encoded photochromic proteins benefit PACT in detection sensitivity and specificity. The unique photoswitching characteristics of different photochromic proteins allow quantitative multi-contrast imaging at depths. A split version of the photochromic protein has permitted PA detection of protein-protein interactions in deep-seated tumors. The photochromic behaviors have also been utilized to guide photons to form an optical focus inside live tissue. As a rapidly evolving imaging technique, PACT promises pre-clinical applications and clinical translation.

Item Type:Thesis (Dissertation (Ph.D.))
Subject Keywords:Biomedical imaging, Photoacoustic tomography, Multicontrast imaging, Deep tissue imaging, Brain, Functional imaging, Molecular imaging
Degree Grantor:California Institute of Technology
Division:Engineering and Applied Science
Major Option:Electrical Engineering
Thesis Availability:Public (worldwide access)
Research Advisor(s):
  • Wang, Lihong
Thesis Committee:
  • Yang, Changhuei (chair)
  • Wang, Lihong
  • Tai, Yu-Chong
  • Shapiro, Mikhail G.
  • Oka, Yuki
Defense Date:5 April 2019
Funders:
Funding AgencyGrant Number
NIH EB016986
NIH CA186567
NIHNS090579
NIHNS099717
NIHEB016963
Record Number:CaltechTHESIS:05072019-120355881
Persistent URL:https://resolver.caltech.edu/CaltechTHESIS:05072019-120355881
DOI:10.7907/FYGX-7M29
Related URLs:
URLURL TypeDescription
https://doi.org/10.1038/s41377-019-0147-9DOIArticle adapted for Chapter 5.
https://doi.org/10.1038/s41467-018-05231-3DOIArticle adapted for Chapter 5.
https://doi.org/10.1038/nmeth.3656DOIArticle adapted for Chapter 5.
https://doi.org/10.1117/1.NPh.3.3.035001DOIArticle adapted for Chapter 4.
https://doi.org/10.1002/jbio.201700024DOIArticle adapted for Chapter 3.
https://doi.org/10.1038/nmeth.3336DOIArticle adapted for Chapter 2.
https://doi.org/10.1117/1.JBO.22.4.041018DOIArticle adapted for Chapter 2.
https://doi.org/10.1137/17M1153649DOIArticle adapted for Chapter 2.
https://doi.org/10.1038/s41551-017-0071DOIArticle adapted for Chapters 2, 4 and 5.
https://doi.org/10.1117/1.JBO.23.3.036007DOIArticle adapted for Chapter 1.
https://doi.org/10.1117/1.JBO.23.7.076001DOIArticle adapted for Chapter 1.
https://doi.org/10.1117/1.JBO.22.4.041017DOIArticle adapted for Chapter 1.
https://doi.org/10.1364/OPTICA.5.000495DOIArticle adapted for Chapter 1.
https://doi.org/10.1117/1.JBO.22.4.041003DOIArticle adapted for Chapter 1.
https://doi.org/10.1117/1.JBO.22.7.076017DOIArticle adapted for Chapter 1.
https://doi.org/10.1002/jbio.201700196DOIArticle adapted for Chapter 1.
https://doi.org/10.1002/anie.201403812DOIArticle adapted for Chapter 1.
https://doi.org/10.1364/OPTICA.1.000217DOIArticle adapted for Chapter 1.
https://doi.org/10.1364/OL.39.002117DOIArticle adapted for Chapter 1.
https://doi.org/10.1117/1.JBO.20.6.066010DOIArticle adapted for Chapter 1.
ORCID:
AuthorORCID
Li, Lei0000-0001-6164-2646
Default Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:11501
Collection:CaltechTHESIS
Deposited By: Lei Li
Deposited On:15 May 2019 16:06
Last Modified:04 Oct 2019 00:25

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