Date of Award
Doctor of Philosophy (PhD)
Surgery remains the only curative option for most solid tumors. The standard-of-care usually involves tumor resection and sentinel lymph node biopsy for cancer staging. Surgeons rely on their vision and touch to distinguish healthy from cancer tissue during surgery, often leading to incomplete tumor resection that necessitates repeat surgery. Sentinel lymph node biopsy by conventional radioactive tracking exposes patients and caregivers to ionizing radiation, while blue dye tracking stains the tissue highlighting only superficial lymph nodes. Improper identification of sentinel lymph nodes may misdiagnose the stage of the cancer. Therefore there is a clinical need for accurate intraoperative tumor and sentinel lymph node visualization.
Conventional imaging modalities such as x-ray computed tomography, positron emission tomography, magnetic resonance imaging, and ultrasound are excellent for preoperative cancer diagnosis and surgical planning. However, they are not suitable for intraoperative use, due to bulky complicated hardware, high cost, non-real-time imaging, severe restrictions to the surgical workflow and lack of sufficient resolution for tumor boundary assessment. This has propelled interest in fluorescence-guided surgery, due to availability of simple hardware that can achieve real-time, high resolution and sensitive imaging. Near-infrared fluorescence imaging is of particular interest due to low background absorbance by photoactive biomolecules, enabling thick tissue assessment. As a result several near-infrared fluorescence-guided surgery systems have been developed. However, they are limited by bulky hardware, disruptive information display and non-matched field of view to the user.
To address these limitations we have developed a compact, light-weight and wearable goggle augmented imaging and navigation system (GAINS). It detects the near-infrared fluorescence from a tumor accumulated contrast agent, along with the normal color view and displays accurately aligned, color-fluorescence images via a head-mounted display worn by the surgeon, in real-time. GAINS is a platform technology and capable of very sensitive fluorescence detection. Image display options include both video see-through and optical see-through head-mounted displays for high-contrast image guidance as well as direct visual access to the surgical bed. Image capture options from large field of view camera as well high magnification handheld microscope, ensures macroscopic as well as microscopic assessment of the tumor bed. Aided by tumor targeted near-infrared contrast agents, GAINS guided complete tumor resection in subcutaneous, metastatic and spontaneous mouse models of cancer with high sensitivity and specificity, in real-time. Using a clinically-approved near-infrared contrast agent, GAINS provided real-time image guidance for accurate visualization of lymph nodes in a porcine model and sentinel lymph nodes in human breast cancer and melanoma patients with high sensitivity. This work has addressed issues that have limited clinical adoption of fluorescence-guided surgery and paved the way for research into developing this approach towards standard-of-care practice that can potentially improve surgical outcomes in cancer.
Lihong Wang, Mark Anastasio, Joseph Culver, Viktor Gruev,