An Integrated Widefield Imaging and Spectroscopy System for Contrast-Enhanced, Image-Guided Resection of Tumors

Abstract

Tumor recurrence following surgery is a common and unresolved medical problem of great importance since surgery is the most widely used treatment for solid-mass tumors worldwide. A contributing factor to tumor recurrence is the presence of residual tumor remaining at or near the surgical site following surgery. Goal The primary objective of this study was to develop and evaluate an image-guided surgery system based on a near infrared, handheld excitation source and spectrograph in combination with a widefield video imaging system. Methods This system was designed to detect the fluorescence of near infrared contrast agents and, in particular, indocyanine green. The imaging system was evaluated for its optical performance and ability to detect the presence of indocyanine green in tumors in an ectopic murine tumor model as well as in spontaneous tumors arising in canines. Results In both settings, an intravenous indocyanine green infusion provided tumor contrast. In both the murine models and surgical specimens from canines, indocyanine green preferentially accumulated in tumor tissue compared to surrounding normal tissue. The resulting contrast was sufficient to distinguish neoplasia from normal tissue; in the canine surgical specimens, the contrast was sufficient to permit identification of neoplasia on the marginal surface of the specimen. Conclusion These results demonstrate a unique concept in image-guided surgery by combining local excitation and spectroscopy with widefield imaging. Significance The ability to readily detect ICG in canines with spontaneous tumors in a clinical setting exemplifies the potential for further clinical translation; the promising results of detecting neoplasia on the marginal specimen surface underscores the clinical utility.

Near Infrared Fluorescent Nanoparticles Derived from Hyaluronic Acid Improve Tumor Contrast for Image-Guided Surgery

“…The bilateral mammary tumors were identified using a combination of visual resection and with the aid of a separate fluorescence image-guided surgery system, termed (FIGSS), resected under image-guidance, then followed by reexamination of the contrast enhancing region. FIGSS, which we have previously described in detail elsewhere 35,36, utilizes two separate, but integrated components. The first is a spectrophotometer that is fiber-coupled to a hand-held device that trasmits 785 nm excitation and collects wavelength-resolved fluorescence emission through the same device 35.…”

“…The version used here is capable of 8 (low), 30 (medium low), 80 (medium), 150 (medium high), and 200 (high) mW power and collects spectra between 800-950 nm. The second component of the system is a real-time video widefield imaging system that collects both NIR emission from the contrast agent and visibile light for anatomical reference 36. The widefield sytem uses the laser from the spectroscopic system as its excitation source.…”

Near infrared fluorescent nanoparticles based on hyaluronic acid: Self-assembly, optical properties, and cell interaction

“…In this case, HA was modified with different hydrophobic ligands to form self-assembled micelle-like structures that could entrap ICG. Although NanoICG demonstrated significantly higher contrast to noise compared to ICG alone, the physical entrapment of ICG has inherent limitations in determining the role and distribution of amphiphilic HA, as ICG can also associate with serum proteins [7,29]. …”

Augmented microscopy: real-time overlay of bright-field and near-infrared fluorescence images

“…The augmented microscope described here uniquely addresses this need in many situations routinely requiring the use of specialized surgical microscopes, such as neurological, cerebrovascular, otolaryngological, and ophthalmic procedures. As such, it complements the ever-increasing range of superb commercial and research devices relying on the synthetic (predominantly falsecolored NIR fluorescence) images projected on auxiliary monitors, [26][27][28] wearable see-through display, 29,30 or dynamic optical projection onto the surgical field 31 introduced recently and excelling in their own applicable medical specialties.…”

“…33 Intraoperative NIR imaging may aid in resection of these challenging tumors. 19,[26][27][28][29][30][31][32][33][34][35][36][37][38][39] The long-term interest in the intraoperative NIR fluorescence visualization is driven by the development of new agents capable of improved delineation of brain tumor margins. Examples of dyes include various derivatives of NIR fluorescent dye currently undergoing preclinical or clinical evaluations, such as BLZ-100, a chlorotoxin-ICG conjugate; 36,37 CLR1502, an alkylphopholine derivative of a cyanine dye; 40,41 anti-EGFR antibody fragments conjugated to IRDye 800 CW; 42,43 and others.…”