Fluorescence guided surgery (FGS), also called fluorescence image-guided surgery, or in the specific case of tumor resection, fluorescence guided resection, is a

medical imaging Medical imaging is the technique and process of imaging the interior of a body for clinical analysis and medical intervention, as well as visual representation of the function of some organs or tissues (physiology). Medical imaging seeks to rev ...

technique used to detect fluorescently labelled structures during surgery. Similarly to standard

image-guided surgery Image-guided surgery (IGS) is any surgical procedure where the surgeon uses tracked surgical instruments in conjunction with preoperative or intraoperative images in order to directly or indirectly guide the procedure. Image guided surgery systems u ...

, FGS has the purpose of guiding the surgical procedure and providing the surgeon of real time visualization of the operating field. When compared to other medical imaging modalities, FGS is cheaper and superior in terms of

resolution Resolution(s) may refer to: Common meanings * Resolution (debate), the statement which is debated in policy debate * Resolution (law), a written motion adopted by a deliberative body * New Year's resolution, a commitment that an individual mak ...

and number of molecules detectable. As a drawback, penetration depth is usually very poor (100 μm) in the visible wavelengths, but it can reach up to 1–2 cm when excitation wavelengths in the

near infrared Infrared (IR), sometimes called infrared light, is electromagnetic radiation (EMR) with wavelengths longer than those of visible light. It is therefore invisible to the human eye. IR is generally understood to encompass wavelengths from around ...

are used.

Imaging devices

FGS is performed using imaging devices with the purpose of providing real time simultaneous information from color

reflectance The reflectance of the surface of a material is its effectiveness in reflecting radiant energy. It is the fraction of incident electromagnetic power that is reflected at the boundary. Reflectance is a component of the response of the electronic ...

images (bright field) and fluorescence emission. One or more light sources are used to excite and illuminate the sample. Light is collected using optical filters that match the emission spectrum of the

fluorophore A fluorophore (or fluorochrome, similarly to a chromophore) is a fluorescent chemical compound that can re-emit light upon light excitation. Fluorophores typically contain several combined aromatic groups, or planar or cyclic molecules with se ...

. Imaging lenses and digital cameras ( CCD or

CMOS Complementary metal–oxide–semiconductor (CMOS, pronounced "sea-moss", ) is a type of metal–oxide–semiconductor field-effect transistor (MOSFET) fabrication process that uses complementary and symmetrical pairs of p-type and n-type MOSFE ...

) are used to produce the final image. Live video processing can also be performed to enhance contrast during fluorescence detection and improve signal-to-background ratio. In recent years a number of commercial companies have emerged to offer devices specializing in fluorescence in the NIR wavelengths, with the goal of capitalizing upon the growth in off label use of indocyanine green (ICG). However commercial systems with multiple fluorescence channels also exist commercially, for use with fluorescein and protoporphyrin IX (PpIX).

Excitation sources

Fluorescence excitation is accomplished using various kind of light sources.

Halogen lamps A halogen lamp (also called tungsten halogen, quartz-halogen, and quartz iodine lamp) is an incandescent lamp consisting of a tungsten filament sealed in a compact transparent envelope that is filled with a mixture of an inert gas and a small ...

have the advantage of delivering high power for a relatively low cost. Using different

band-pass filters A band-pass filter or bandpass filter (BPF) is a device that passes frequencies within a certain range and rejects (attenuates) frequencies outside that range. Description In electronics and signal processing, a filter is usually a two-po ...

, the same source can be used to produce several excitation channels from the UV to the near infrared.

Light-emitting diodes A light-emitting diode (LED) is a semiconductor device that emits light when current flows through it. Electrons in the semiconductor recombine with electron holes, releasing energy in the form of photons. The color of the light (cor ...

(LEDs) have become very popular for low cost broad band illumination and narrow band excitation in FGS. Because of their characteristic light emission spectrum, a narrow range of wavelengths that matches the absorption spectrum of a given

can be selected without using a filter, further reducing the complexity of the optical system. Both halogen lamps and LEDs are suitable for white light illumination of the sample. Excitation can also be performed using

laser diodes The laser diode chip removed and placed on the eye of a needle for scale A laser diode (LD, also injection laser diode or ILD, or diode laser) is a semiconductor device similar to a light-emitting diode in which a diode pumped directly with e ...

, particularly when high power over a short wavelength range (typically 5-10 nm) is needed. In this case the system has to account for the limits of exposure to laser radiation.

Detection techniques

Live images from the fluorescent dye and the surgical field are obtained using a combination of filters, lenses and cameras. During

open surgery Minimally invasive procedures (also known as minimally invasive surgeries) encompass surgical techniques that limit the size of incisions needed, thereby reducing wound healing time, associated pain, and risk of infection. Surgery by definition ...

, hand held devices are usually preferred for their ease of use and mobility. A stand or arm can be used to maintain the system on top of the operating field, particularly when the weight and complexity of the device is high (e.g. when multiple cameras are used). The main disadvantage of such devices is that operating theater lights can interfere with the fluorescence emission channel, with a consequent decrease of signal-to-background ratio. This issue is usually solved by dimming or switching off the theater lights during fluorescence detection. FGS can also be performed using minimally invasive devices such as laparoscopes or

endoscopes An endoscopy is a procedure used in medicine to look inside the body. The endoscopy procedure uses an endoscope to examine the interior of a hollow organ or cavity of the body. Unlike many other medical imaging techniques, endoscopes are inse ...

. In this case, a system of filters, lenses and cameras is attached to the end of the probe. Unlike open surgery, the background from external light sources is reduced. Nevertheless, the excitation power density at the sample is limited by the low light transmission of the

fiber optics An optical fiber, or optical fibre in Commonwealth English, is a flexible, transparent fiber made by drawing glass (silica) or plastic to a diameter slightly thicker than that of a human hair. Optical fibers are used most often as a means to ...

in endoscopes and laparoscopes, particularly in the near infrared. Moreover, the ability of collecting light is much reduced compared to standard imaging lenses used for open surgery devices. FGS devices can also be implemented for

robotic surgery Robotic surgery are types of surgical procedures that are done using robotic systems. Robotically assisted surgery was developed to try to overcome the limitations of pre-existing minimally-invasive surgical procedures and to enhance the capabil ...

(for example in the

da Vinci Surgical System The Da Vinci Surgical System is a robotic surgical system that uses a minimally invasive surgical approach. The system is manufactured by the company Intuitive Surgical. The system is used for prostatectomies, and increasingly for cardiac ...

Clinical applications

The major limitation in FGS is the availability of clinically approved fluorescent dyes which have a novel biological indication.

Indocyanine green Indocyanine green (ICG) is a cyanine dye used in medical diagnostics. It is used for determining cardiac output, hepatic function, liver and gastric blood flow, and for ophthalmic angiography.

(ICG) has been widely used as a non-specific agent to detect

sentinel lymph node The sentinel lymph node is the hypothetical first lymph node or group of nodes draining a cancer. In case of established cancerous dissemination it is postulated that the sentinel lymph nodes are the target organs primarily reached by metastasiz ...

s during surgery. ICG has the main advantage of absorbing and emitting light in the near infrared, allowing detection of nodes under several centimeters of tissue.

Methylene blue Methylthioninium chloride, commonly called methylene blue, is a salt used as a dye and as a medication. Methylene blue is a thiazine dye. As a medication, it is mainly used to treat methemoglobinemia by converting the ferric iron in hemoglobin ...

can also be used for the same purpose, with an excitation peak in the red portion of the spectrum. First clinical applications using tumor-specific agents that detect deposits of ovarian cancer during surgery have been carried out.

History

The first uses of FGS dates back to the 1940s when fluorescein was first used in humans to enhance the imaging of brain tumors, cysts, edema and blood flow in vivo. In modern times the use has fallen off, until a multicenter trial in Germany concluded that FGS to help guide glioma resection based upon fluorescence from PpIX provided significant short-term benefit.

References