(30 Lines) Frozen section diagnoses are typically requested intraoperatively to guide the surgery. While this methodology is still irreplaceable, it suffers from a series of limitations: tissue loss, freezing artifacts, suboptimal cutting of fatty specimens, inability to diagnose bony lesions, and prolonged turnaround time.
The aim i s to develop a multi-channel subcellular resolution photoacoustic microscopy (PAM) system capable of addressing all the aforementioned limitations and providing pathologists with diagnostic images comparable or identical to the state of the art, with magnification matching or exceeding that of standard transmission light microscopes, and requiring no additional training for pathologists to diagnose. To achieve our objective, we will pursue the following two specific aims:
Specific Aim 1 : Develop a multi-channel subcellular resolution PAM system for rapid analysis and diagnosis of tissue biopsies A. Develop a multi-channel subcellular resolution PAM system B. Develop a customized tissue biopsy holder for rapid tissue biopsy handling and imaging by PAM Specific Aim 2: Optimize and validate the multi-channel subcellular resolution PAM for translation into a robust, accurate, and efficient intraoperative device A. Optimize image acquisition in order to maximize discrimination of nuclear, cytoplasmic, and stromal properties with minimal tissue degradation B. Optimize post-acquisition algorithms to generate pseudocolored images resembling classical hematoxylin and eosin (H&E) sections with superimposed unique imaging modalities (edema and collagen) C. Validate the utilization of PAM generated images for diagnostic purposes by comparing with H&E sections, which are prepared by formalin-fixed paraffin-embedding (the current gold standard) D. Validate the utilization of PAM generated images for intraoperative diagnostic purposes by comparing with H&E sections, which are prepared by frozen section (the current intraoperative gold standard) Impact: The proposed technology will represent a major breakthrough by addressing all the limitations of current frozen section-based diagnoses and providing images with H&E equivalent qualities intraoperatively.
It aims to introduce a rapid and tissue saving diagnostic method for surgical biopsies, positively impacting the healthcare system and patient care. Reducing the turnaround time on the frozen section interpretation will significantly reduce the time spent in the operating room, and therefore, decrease patient risks and costs. The ability to evaluate adequacy of small specimens with no loss in tissue will decrease the need for re-biopsy procedures. The virtually generated images can be interpreted remotely so that smaller hospitals can benefit from procedures currently available only to larger tertiary hospitals and university centers.

Public Health Relevance

(Three Sentences) Currently, rapid interpretation of tissue biopsies, is performed by frozen section, a suboptimal methodology requiring specialized personnel and associated with relatively long turn-around time, tissue loss and processing artifacts, compromising the diagnostic interpretation. If successfully implemented, the proposed photoacoustic microscope, will decrease patient's risks and costs, by improving the turnaround time on intraoperative diagnoses, reducing the time spent in the operating room and by decreasing the need for re-biopsy procedures, due the ability to evaluate adequacy of small specimens with no loss in tissue. Furthermore, the virtually generated images can be interpreted remotely, so that smaller hospitals can benefit from procedures currently available only to larger tertiary hospitals and university centers.

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Research Project (R01)
Project #
5R01EB028277-02
Application #
9952369
Study Section
Imaging Technology Development Study Section (ITD)
Program Officer
King, Randy Lee
Project Start
2019-07-01
Project End
2023-03-31
Budget Start
2020-04-01
Budget End
2021-03-31
Support Year
2
Fiscal Year
2020
Total Cost
Indirect Cost
Name
California Institute of Technology
Department
Engineering (All Types)
Type
Biomed Engr/Col Engr/Engr Sta
DUNS #
009584210
City
Pasadena
State
CA
Country
United States
Zip Code
91125