Incomplete tumor resection is a major factor that compromise long-term survival rate of cancer patients. Fluorescence-guided surgery is an emerging technology that holds great potential to provide a viable solution to this problem. In this study, we developed and demonstrated the use of a new device that can detect non-obvious small tumor lesions, guide SLN biopsy and allow remote telemedical guidance.
To date, most fluorescence-guided intraoperative imaging modalities are limited to 2-D planar imaging due to the technical difficulties in implementing tomography in real time. In reality, 2-D imaging systems do not provide sufficient depth-information to guide surgery that is 3-D in essence. Although a 2-D functional-anatomical composite image could be projected on a monitor10, 25
, surgeons still use naked eyes to survey the actual tissue anatomical landscape in real time. To overcome this obstacle, our system is designed as a goggle device that does not require remote display on a computer monitor. During operation, surgeons can simultaneously view the functional status in the eyepiece with one eye and obtain the anatomical information to navigate the region of interest with the unaided eye.
Without cost-effectiveness, any image-guided technology could not be readily translated into clinics on a global scale, regardless of its efficacy. Hence, an important component of our design process was to reduce the instrument cost and size, with the long-term goal of extending its use to underserved populations and rural areas. For instance, instead of building a detector from high-end scientific grade cameras that are generally large and expensive such as FLARE10
and Hamamatsu Photodynamic Eye26
, the detector portion of the device was developed from a CCD-based consumer-grade night vision viewer. We have demonstrated the detector is able to provide high detection sensitivity in vivo
along with low cost and compact size.
The detector operates on four AA batteries and offers 10 levels of adjustable gain settings. Each gain setting corresponds to a dynamic range of signal amplification that automatically optimizes and displays the detected NIR light level. This dynamic amplification feature is crucial for surgical applications, as it automatically optimizes and normalizes the fluorescence intensity displayed in real time. This circumvents the need to tediously re-adjust settings manually with specialized image-processing software in the dynamically changing surgical environment. In addition, the simple gain-setting control on the device allows the surgeon to manage the device directly, without the assistance of other personnel. These features could significantly simplify the procedures and lower the labor cost in the OR.
We demonstrated that the prototype device provides high detection sensitivity and signal-to-background contrast, which can help surgeons to locate non-obvious small cancerous lesions and SLNs. When utilized in tumor resection, the device detected tumor margins, small nodules, and some residual tumors that are not detectable with the unaided eye. This approach may improve surgical margins by reduce the size of healthy tissues resected, minimize the probability of incomplete resection, and decrease the need for follow-up surgery. When employed in SLN mapping, the device can clearly indicate the positions of SLNs even with tracer level dosing of indocyanine green, which circumvents the potential side effects caused by radioactive tracers and blue dyes.
In this study, wireless communication is enabled by integrating a battery-operated miniature RF video transmitter into the system to test initial feasibility of this concept. Coupling our device to standard communication platforms such as 3-G will facilitate real-time visual/auditory collaborative relations, as demonstrated in this study. Thus, direct communication can be made between clinicians at leading medical institutions and their counterparts in rural or remote areas, even across continents. The total cost of the prototype system is approximately $1,200, up to 100 times less than previously reported intraoperative fluorescence imaging systems such as FLARE™ (approximately $120,000)10
, Hamamatsu Photodynamic Eye (approximately $40,000)26
and GE FIGS system (approximately $15,000)25
There are limitations to the study. Murine models were used to demonstrate the feasibility of image-guided SLN biopsy and tumor resection with our device. However, large animal models are needed to simulate human studies, which is the subject of a second-generation device. Additionally, the monocular visualization system may affect depth perception and require surgeons to use their dominant eyes for the goggle piece. This may present some logistical problems for the surgeon. Finally, our first prototype is not the optimal ergonomic design for any surgeon. In this prototype, we aim to demonstrate the concept rather than translating it into clinics in its current form. The next generation device will be smaller, lighter, with more functionalities and better ergonomics.
In summary, we have demonstrated the development and feasibility of using a hands-free and wireless device for NIR fluorescence-guided surgery. The device facilitated tumor resection and SLNs biopsy procedures. Furthermore, the device is affordable, portable, user-friendly, and provides the surgeon with wireless communication in a telemedicine setting, facilitating its potential use in rural clinics and point-of-care settings, where inexperienced clinicians may perform complex surgical procedures under real-time remote guidance of expert surgeons and physicians.