Dynamic contrast enhanced photoacoustic computed tomography in MDA-MB-231 and BT-474 xenograft tumor models

Michael Richardson Shaffer, Purdue University

Abstract

Purpose: The objective of the research is to determine the feasibility of the prototype photoacoustic scanner to quantify localized blood perfusion and fractional plasma volume in vivo utilizing an exogenous dye within a breast cancer xenograft tumor model coupled with a dynamic contrast enhanced imaging protocol. ^ Methods and Materials: The prototype photoacoustic scanner was tested for motion artifacts during individual scans that exceeded the 154 micron theoretical spatial resolution utilizing phantoms. The laser optical delivery system was also tested and optimized to minimize non-uniformities over the field of view. An isoflurane anesthetic delivery and scavenge system were designed and added to the scanner. Animal models were developed using the breast cancer cell lines MB-MDA-231 and BT-474. These were xenografted onto athymic nude mice. A synthesized arterial input function was produced utilizing measurements obtained with DCE-CT scans. 4D image coregistration was performed to allow for measuring identical regions between DCE-CT and DCE-PCT scans. This data was then able to be used for compartmental modeling of dynamic contrast enhanced photoacoustic data. The perfusion and fractional plasma volume values as determined by DCE-PCT were then able to be compared to the values as measured by DCE-CT. A series of fiber optic dosimetry probes were also fabricated and calibrated to aid in measuring laser fluence within the photoacoustic scanner. ^ Results: The photoacoustic scanner was adjusted to have in scan motion less than that of the theoretical spatial resolution. The synthesized arterial input function was determined to have the same general shape, and peak timing as that of individual arterial input functions measured by both DCE-CT and DCE-PCT scans. A fiber optic dosimetry probe with a diameter of 1.5mm and a concentration of 5mg/mL titanium dioxide was determined to yield a coefficient of variation of ∼7%. Compartmental fitting after coregistration was performed to determine blood perfusion and fractional plasma volume. ^ Conclusion: This study explored the feasibility of a prototype photoacoustic scanner to quantify localized blood perfusion and fractional plasma volume in vivo using a dynamic contrast enhanced imaging protocol in a xenograft tumor model. The perfusion and fractional plasma volumes determined by DCE-PCT did not obtain statistically significant correlation to those same measurements as determined by DCE-CT.^

Degree

Ph.D.

Advisors

Keith M. Stantz, Purdue University.

Subject Area

Health Sciences, Radiology|Health Sciences, Oncology

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