Abstract

Colorectal cancer is the second leading cause of cancer death in the United States. Significant limitations in screening and surveillance modalities continue to hamper early detection of primary cancers or recurrences after therapy. In this study, we describe a new registered ultrasound (US) and acoustic-resolution photoacoustic microscopy (AR-PAM) system and report its initial testing in ex vivo human colorectal tissue. A total of 8 colorectal specimens were imaged, which included 2 polyps, 4 malignant colon cancers, and 2 treated colorectal cancers. In each specimen, normal tissue was also imaged for internal control. Initial data have demonstrated the feasibility of identifying colorectal cancer imaging features and the invasion depth using co-registered US and an AR-PAM system. In normal tissue, we found that our system consistently demonstrates the multi-layer structure of normal colonic tissue while differentiating layers with elevated vascularity; these findings highly correlated with histologic findings of each specimen. For malignant colorectal samples, the tissue structure is highly disorganized as seen in US, and photoacoustic imaging revealed distorted vascular distribution inside the tumor. Notably, AR-PAM of tumor beds after complete tumor destruction by radiation and chemotherapy yielded a pattern identical to benign tissue. Quantitative analysis of photoacoustic spectral slope has demonstrated more high-frequency components in malignant tissue as compared to the normal colon tissue, which may be caused by significantly increased microvessel networks. In summary, we demonstrate the successful differentiation of benign and malignant colorectal tissue with our co-registered ultrasound and photoacoustic system.

Highlights

  • Photoacoustic imaging (PAI) techniques have demonstrated a unique ability to resolve optical absorption contrast in biological tissues [1,2], which can be invaluable for detection and diagnosis of tumor microvasculature or tumor angiogenesis [3,4]

  • Photoacoustic microscopy (PAM) is classified into optical-resolution (OR) photoacoustic microscopy (PAM) and acoustic-resolution (AR) PAM [6]; acoustic-resolution photoacoustic microscopy (AR-PAM) is able to penetrate deeper than ORPAM due to the use of acoustic focusing rather than optical focusing through tissue

  • In addition to qualitatively describing the appearance of various histology when imaged with this system, we report a method for quantitatively analyzing the different tissue profiles. These results suggest that AR-PAM may offer new discriminatory data to clinicians attempting to differentiate malignant from normal tissue in the human colon and rectum

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Summary

Introduction

Photoacoustic imaging (PAI) techniques have demonstrated a unique ability to resolve optical absorption contrast in biological tissues [1,2], which can be invaluable for detection and diagnosis of tumor microvasculature or tumor angiogenesis [3,4]. PAI technique is based on the photoacoustic principle: as pulsed laser is delivered to tissue, photon energy absorbed by biomolecules converts to heat and creates an initial pressure wave [5]. This wave is detectable by an ultrasonic transducer. PAI transforms hemoglobin into an endogenous contrast agent that can be used to determine various functional and anatomic characteristics not available with basic endoscopy. PAI has the potential to detect, in real time, both anatomic and functional changes that are otherwise not captured by traditional radiographic techniques

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