Since the first x-ray was taken in 1895, medical imaging has progressed rapidly in the world of healthcare. Preoperative imaging is extremely useful for and widely utilized in surgical planning, but it may not provide a complete picture. For example, images may be mistakenly identified as other structures, or changes in the patient may occur in the time from the imaging session to the surgery. To mitigate these issues and provide better visualization, intraoperative imaging techniques can aid the surgeon during the surgical procedure.1 Fluorescence guided surgery is one method to improve visualization and precision for surgeons.
Fluorescence-based techniques provide real-time visual information to the surgeon through the fluorescence intensity of a probe. A fluorescence-guided system (FGS) consists of a fluorescence contrast agent (called a fluorophore), a light source to excite the fluorophore, appropriate light filters, and auxiliary visualization equipment. When the probe emits the fluorescence signal, it is first passed through emissions filters to remove excitation light and autofluorescence and then transferred to the attached computer.1 FGS are less expensive and more portable than other imaging techniques like MRI and CT, which enables FGS to be brought into and removed from the surgical environment as needed. FGS are also more intuitive, reducing the need for specially trained personnel. Their high contrast, intuitive operation, ease of image acquisition, and high molecular selectivity in applications, such as identifying cancer cells, make fluorescence guided surgery an important tool for clinicians.2
Indocyanine green (ICG) is a sterile, anionic, hydrophobic, tri-carbocyanine molecule commonly used as a fluorophore in clinical and laboratory settings. Following IV injection, ICG rapidly binds to plasma proteins, especially lipoproteins. When injected outside of blood vessels, ICG initially attaches to lymph proteins, which travels to the nearest draining lymph node, and is finally taken up by macrophages.3 Since its approval by the FDA in 1959, ICG has been used to determine cardiac output, hepatic function, and liver blood flow. The agent has also been approved for ophthalmic angiography. In a report of laparoscopic cholecystectomy on 52 patients, ICG injection and fluorescence made it possible to outline the biliary tree anatomy, especially at the cystic duct. The team reported no adverse effects or complications in their patient group. ICG has also been used to clarify the vascular anatomy in the renal system and identify ischemic parenchyma during laparoscopic living-donor nephrectomy, laparoscopic kidney auto-transplantation for renal artery aneurysm, splenectomy, and liver resection. Another application of
fluorescence guided surgery using ICG is laparoscopic ligation of the inferior mesenteric artery after endovascular repair of an aortic aneurysm.3
In oncology, maximal tumor resection leads to reduced reliance on further cancer therapies, such as radiotherapy and chemotherapy, and significantly improved patient outcomes and quality of life. Using fluorescence guided surgery can improve the chances of maximal resection by providing real-time visual information to the surgeon.4 In a landmark 2006 RCT on suspected high-grade gliomas, 322 patients were randomly assigned to fluorescence-guided resection with 5-aminolevulinic acid (5-ALA) or conventional microsurgery with white light. 5-ALA, which accumulates intracellularly in tumor cells and has a high affinity for high-grade glioma tissue, is a precursor to protoporphyrin IX (PPIX), which fluoresces at 635 nm. Complete tumor resection was achieved in 65% of patients assigned to the FGS group, compared to 36% of patients assigned to the conventional surgery group. Patients given 5-ALA also had higher 6-month progression free survival.5 Following the publication of this multicenter trial, the use of 5-ALA for glioma resection has increased significantly. Recent studies have suggested that 5-ALA fluorescence may have a longer window of detection than other fluorophores. A wider window of adequate fluorescence enables greater flexibility, which is clinically relevant as surgeries are often delayed due to logistical challenges or emergent cases.6
Fluorescence guided surgery, through agents such as ICG and 5-ALA, offers surgeons real-time insights that can enhance the precision of tumor resections, open laparoscopies, and other critical procedures. As evidence mounts regarding the benefits of these guided surgeries, their adoption is likely to expand, paving the way for more precise and minimally invasive surgical interventions.
References
1. Stewart, Hazel L., and David J. S. Birch. “Fluorescence Guided Surgery.” Methods and Applications in Fluorescence, vol. 9, no. 4, Oct. 2021, p. 042002. https://doi.org/10.1088/2050-6120/ac1dbb
2. DeLong, Jonathan C., et al. “Current Status and Future Perspectives of Fluorescence-Guided Surgery for Cancer.” Expert Review of Anticancer Therapy, vol. 16, no. 1, Jan. 2016, pp. 71–81. https://doi.org/10.1586/14737140.2016.1121109.
3. Boni, Luigi, et al. “Clinical Applications of Indocyanine Green (ICG) Enhanced Fluorescence in Laparoscopic Surgery.” Surgical Endoscopy, vol. 29, no. 7, July 2015, pp. 2046–55. https://doi.org/10.1007/s00464-014-3895-x
4. Neira, Justin A., et al. “Aggressive Resection at the Infiltrative Margins of Glioblastoma Facilitated by Intraoperative Fluorescein Guidance.” Journal of Neurosurgery, vol. 127, no. 1, July 2017, pp. 111–22. https://doi.org/10.3171/2016.7.JNS16232
5. Stummer, Walter, et al. “Fluorescence-Guided Surgery with 5-Aminolevulinic Acid for Resection of Malignant Glioma: A Randomised Controlled Multicentre Phase III Trial.” The Lancet Oncology, vol. 7, no. 5, May 2006, pp. 392–401. https://doi.org/10.1016/S1470-2045(06)70665-9.
6. Schupper, Alexander J., et al. “Fluorescence-Guided Surgery: A Review on Timing and Use in Brain Tumor Surgery.” Frontiers in Neurology, vol. 12, June 2021. https://doi.org/10.3389/fneur.2021.682151