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Prediction of tumor recurrence and therapy monitoring using ultrasound-guided photoacoustic imaging.

ABSTRACT: Selection and design of individualized treatments remains a key goal in cancer therapeutics; prediction of response and tumor recurrence following a given therapy provides a basis for subsequent personalized treatment design. We demonstrate an approach towards this goal with the example of photodynamic therapy (PDT) as the treatment modality and photoacoustic imaging (PAI) as a non-invasive, response and disease recurrence monitor in a murine model of glioblastoma (GBM). PDT is a photochemistry-based, clinically-used technique that consumes oxygen to generate cytotoxic species, thus causing changes in blood oxygen saturation (StO2). We hypothesize that this change in StO2 can be a surrogate marker for predicting treatment efficacy and tumor recurrence. PAI is a technique that can provide a 3D atlas of tumor StO2 by measuring oxygenated and deoxygenated hemoglobin. We demonstrate that tumors responding to PDT undergo approximately 85% change in StO2 by 24-hrs post-therapy while there is no significant change in StO2 values in the non-responding group. Furthermore, the 3D tumor StO2 maps predicted whether a tumor was likely to regrow at a later time point post-therapy. Information on the likelihood of tumor regrowth that normally would have been available only upon actual regrowth (10-30 days post treatment) in a xenograft tumor model, was available within 24-hrs of treatment using PAI, thus making early intervention a possibility. Given the advances and push towards availability of PAI in the clinical settings, the results of this study encourage applicability of PAI as an important step to guide and monitor therapies (e.g. PDT, radiation, anti-angiogenic) involving a change in StO2.

SUBMITTER: Mallidi S

PROVIDER: S-EPMC4279192 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Prediction of tumor recurrence and therapy monitoring using ultrasound-guided photoacoustic imaging.

Mallidi Srivalleesha S Watanabe Kohei K Timerman Dmitriy D Schoenfeld David D Hasan Tayyaba T

Theranostics 20150101 3

Selection and design of individualized treatments remains a key goal in cancer therapeutics; prediction of response and tumor recurrence following a given therapy provides a basis for subsequent personalized treatment design. We demonstrate an approach towards this goal with the example of photodynamic therapy (PDT) as the treatment modality and photoacoustic imaging (PAI) as a non-invasive, response and disease recurrence monitor in a murine model of glioblastoma (GBM). PDT is a photochemistry- ...[more]

PMID: 25553116

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Project description:As increasing effort is dedicated to investigating the regenerative capacity of decellularized tissues, research has progressed to recellularizing these tissues prior to implantation. The delivery and support of cells seeded throughout acellular scaffolds are typically conducted through the vascular axis of the tissues. However, it is unclear how cell concentration and injection frequency can affect the distribution of cells throughout the scaffold. Furthermore, what effects re-endothelialization have on vascular patency and function are not well understood. We investigated the use of ultrasound-guided photoacoustic (US/PA) imaging as a technique to visualize the distribution of microvascular endothelial cells within an optimized acellular construct upon re-endothelialization and perfusion conditioning. We also evaluated the vascular performance of the re-endothelialized scaffold using quantitative vascular corrosion casting (qVCC) and whole-blood perfusion. We found US/PA imaging was an effective technique to visualize the distribution of cells. Cellular retention following perfusion conditioning was also detected with US/PA imaging. Finally, we demonstrated that a partial recovery of vascular performance is possible following re-endothelialization-confirmed by fewer extravasations in qVCC and improved blood clearance following whole-blood perfusion.Statement of significanceRe-endothelialization is a method that enables decellularized tissue to become useful as a tissue engineering construct by creating a nutrient delivery and waste removal system for the entire construct. Our approach utilizes a decellularization method that retains the basement ECM of a highly vascularized tissue upon which endothelial cells can be injected to form an endothelium. The US/PA method allows for rapid visualization of cells within a construct several cm thick. This approach can be experimentally used to observe changes in cellular distribution over large intervals of time, to help optimize cell seeding parameters, and to verify cell retention within re-endothelialized constructs. This approach has temporal and depth advantages compared to section reconstruction and imaged fluorophores respectively.

Dataset Information

Prediction of tumor recurrence and therapy monitoring using ultrasound-guided photoacoustic imaging.

Publications

Prediction of tumor recurrence and therapy monitoring using ultrasound-guided photoacoustic imaging.

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