Vibrational photoacoustic tomography: Deep tissue imaging with biomarker sensitivity
Abstract
As a molecular and functional imaging modality, photoacoustic imaging has been applied to animals or human organs such as breast, brain and skin. Till now, the contrast mechanism of photoacoustic imaging is mainly based on electronic absorption in visible and near infrared region. Inherent molecular vibration offers a contrast mechanism for chemical imaging in a label free manner. In vibrational microscopy based on either infrared absorption or Raman scattering, the imaging depth is limited to the ballistic photon mean free path, which is a few hundred microns in a biological sample. Owing to much weaker acoustic scattering in tissues as compared to optical scattering, photoacoustic detection of harmonic molecular vibration has enabled significant improvement in imaging depth. Broad use of this modality is, however, hampered by the extremely low conversion efficiency of optical parametric oscillators at the overtone transition wavelengths. My thesis work aimed to overcome such barrier through construction of a high-energy Raman laser and proof-of-concept demonstration of vibrational photoacoustic tomography. Our Raman laser is based on the process of stimulated Raman scattering in a gain medium. The output wavelength of a Raman laser was determined by the pump wavelength and Raman shifts of the medium. Using a 5-ns Nd:YAG laser as the pumping source, up to 21.4 mJ pulse energy at 1197 nm was generated, corresponding to a conversion efficiency of 34.8%. Using the 1197 nm pulses, three-dimensional photoacoustic imaging of intramuscular fat was demonstrated. Further, by using a larger Ba(NO3)2 crystal and no prior focusing of input laser, I recently constructed a new Raman laser, which could produce stable laser pulses at 1197 nm with maximum pulse energy exceeding 100 mJ. Using the new Raman laser, we demonstrated proof-of-concept of vibrational photoacoustic tomography with C-H rich polyethylene tube phantom placed under 3 cm thick chicken breast tissue. Furthermore, by modification of a commercial ultrasound machine, photoacoustic/ultrasound dual-modality real-time in vivo imaging of biological tissues is fulfilled (unpublished). These developments open exciting opportunities of performing label free vibrational imaging in the deep tissue regime.
Degree
M.S.B.M.E.
Advisors
Cheng, Purdue University.
Subject Area
Biomedical engineering|Medical imaging
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