Evgenia Mikhailovna Kim

Dual-mode laparoscopic fluorescence image-guided surgery using a single camera

Iatrogenic nerve damage is a leading cause of morbidity associated with many common surgical procedures. Complications arising from these injuries may result in loss of function and/or sensation, muscle atrophy, and chronic neuropathy. Fluorescence image-guided surgery offers a potential solution for avoiding intraoperative nerve damage by highlighting nerves that are otherwise difficult to visualize. In this work we present the development of a single camera, dual-mode laparoscope that provides near simultaneous display of white-light and fluorescence images of nerves. The capability of the instrumentation is demonstrated through imaging several types of in situ rat nerves via a nerve specific contrast agent. Full color white light and high brightness fluorescence images and video of nerves as small as 100 µm in diameter are presented.

A compact fluorescence and white light imaging system for intraoperative visualization of nerves

Fluorescence image guided surgery (FIGS) allows intraoperative visualization of critical structures, with applications spanning neurology, cardiology and oncology. An unmet clinical need is prevention of iatrogenic nerve damage, a major cause of post-surgical morbidity. Here we describe the advancement of FIGS imaging hardware, coupled with a custom nerve-labeling fluorophore (GE3082), to bring FIGS nerve imaging closer to clinical translation. The instrument is comprised of a 405nm laser and a white light LED source for excitation and illumination. A single 90 gram color CCD camera is coupled to a 10mm surgical laparoscope for image acquisition. Synchronization of the light source and camera allows for simultaneous visualization of reflected white light and fluorescence using only a single camera. The imaging hardware and contrast agent were evaluated in rats during in situ surgical procedures.

Improved Intraoperative Visualization of Nerves through a Myelin-Binding Fluorophore and Dual-Mode Laparoscopic Imaging

The ability to visualize and spare nerves during surgery is critical for avoiding chronic morbidity, pain, and loss of function. Visualization of such critical anatomic structures is even more challenging during minimal access procedures because the small incisions limit visibility. In this study, we focus on improving imaging of nerves through the use of a new small molecule fluorophore, GE3126, used in conjunction with our dual-mode (color and fluorescence) laparoscopic imaging instrument. GE3126 has higher aqueous solubility, improved pharmacokinetics, and reduced non-specific adipose tissue fluorescence compared to previous myelin-binding fluorophores. Dosing and kinetics were initially optimized in mice. A non-clinical modified Irwin study in rats, performed to assess the potential of GE3126 to induce nervous system injuries, showed the absence of major adverse reactions. Real-time intraoperative imaging was performed in a porcine model. Compared to white light imaging, nerve visibility was enhanced under fluorescence guidance, especially for small diameter nerves obscured by fascia, blood vessels, or adipose tissue. In the porcine model, nerve visualization was observed rapidly, within 5 to 10 minutes post-intravenous injection and the nerve fluorescence signal was maintained for up to 80 minutes. The use of GE3126, coupled with practical implementation of an imaging instrument may be an important step forward in preventing nerve damage in the operating room.

PD13-08 EVALUATION OF NERVE-HIGHLIGHTING CONTRAST AGENT GE3126 FOR IMAGE-GUIDED SURGERY

INTRODUCTION AND OBJECTIVES: Inadvertent injury to nerves is a significant and often inevitable consequence of surgery that can lead post-operative morbidity and loss of function. Nerve-sparing during radical prostatectomy can reduce the incidence of post-surgical erectile dysfunction. In retroperitoneal lymph node dissection for testis cancer, the prospective identification and preservation of nerves in is essential in maintaining ejaculatory function and fertility. Although there is a significant need, there is no widely adopted system for real-time identification of nerves in either the open or laparoscopic surgical settings. We sought to investigate the performance of a myelin-targeted fluorophore and optical imaging instrumentation in the intraoperative visualization of nerves. METHODS: A myelin-targeting small molecule fluorophore, GE3126, was synthesized and characterized for its optical and myelinbinding properties using purified myelin basic protein. 2 Yorkshire pigs were utilized in a non-survival study. Peripheral and retroperitoneal nerves were exposed and control images taken using a dedicated compact imaging device adapted to both open and minimally-invasive approaches. Both white light and 405nm illumination were used. Following intravenous injection of the agent, blood, urine, and bile were drawn at fixed intervals to determine the pharmacokinetics of the agent. Central and peripheral nerves were visualized. Tissues were harvested for ex-vivo analysis and histopathology. 4 blinded observers evaluated captured images. RESULTS: The primary route of excretion was renal. The fluorescence peak was achieved at 60-80 min following injection. Label/nonlabel fluorescence signal ratio was 5:1 at peak. Nerve to muscle signal was 7:1. Fluorescence polarization showed specific and strong binding to purified myelin basic protein. Retroperitoneal nerves from 100mm-10mm were evaluated. Inter-observer disagreement was 22% with white light images, and 0% with fluorescence images, which was confirmed by histology. No adverse effects were noted in the animals. CONCLUSIONS: GE3126 provides a safe and effective means of identifying nerves through fluorescence imaging and is adaptable to both open and minimally invasive surgical procedures.

Recent Progress on Micro-holographic Data

Advances in micro-holographic materials and systems are presented. New materials show improved index change (10x) and sensitivity (100x) at >3x lower intensity vs. previously reported. Experimental results supporting single-sided optical drive concept is presented.