Since the first research paper on fluorescence-guided surgery (FGS) was published in 1958, the field
has undergone remarkable transformation. What began as a pioneering idea has transformed into a
critical tool in modern surgical practices, particularly in oncology, neurosurgery and vascular/
perfusion interventions. By the end of 2024, there have been 20,445 peer-reviewed papers
published in PubMed relating to indocyanine green (ICG), highlighting the extensive body of research
underpinning its applications. The cumulative knowledge amassed over decades has not only
advanced surgical precision but also saved countless lives.
This article provides a brief walk through its historical journey, scientific breakthroughs and future
potential of fluorescence-guided surgery, highlighting the rich legacy of knowledge built up over
more than seven decades.
The Early Years: A Seed is Planted
The 1950s marked the inception of fluorescence imaging in surgery with the introduction of
fluorescein, a fluorescent dye that absorbs blue light and emits green light. Early studies explored its
use in mapping vascular perfusion and identifying ischemic tissues. These experiments were
rudimentary by today’s standards, limited by primitive imaging systems and an incomplete
understanding of fluorescence chemistry. Nevertheless, the foundational concept—using light to
visualise structures invisible to the naked eye—set the stage for a paradigm shift in surgery.
A key milestone during this era was the recognition of fluorescence as a tool for tumour delineation.
Researchers observed that certain dyes preferentially accumulated in tissues, offering a potential
means to distinguish cancerous cells from healthy ones. Although the clinical application was still a
distant goal, these early investigations laid the groundwork for decades of research to come.
The 1980s and 1990s: Technological Breakthroughs
The subsequent decades witnessed exponential growth in fluorescence-guided surgery, driven by
technological advancements in imaging systems. In the 1980s, the introduction of near-infrared
(NIR) fluorescence imaging marked a pivotal moment. Unlike visible light, NIR light penetrates
deeper into tissues, allowing for better visualisation of internal structures with minimal interference
from surrounding tissue autofluorescence.
During this time, indocyanine green (ICG) emerged as a game-changing dye. Originally approved for
use in ophthalmology and liver function testing, ICG’s properties—such as its safety profile, rapid
clearance, and strong NIR fluorescence—made it an ideal candidate for surgical applications. It
became widely used for mapping blood flow, identifying sentinel lymph nodes, and assessing tissue
perfusion during procedures like coronary artery bypass grafting.
In parallel, advancements in imaging hardware, such as laparoscopic and endoscopic fluorescence
systems, enabled real-time visualisation during minimally invasive surgeries. These innovations
greatly expanded the scope of FGS, bringing it closer to widespread clinical adoption. When
surgeons transitioned from open to laparoscopic procedures, the capabilities provided by ICG and
fluorescence systems more than compensated for the loss of tactile feedback, which had been a
valuable feature of open surgeries.
UltraGreen.ai
info@ultragreen.ai www.ultragreen.ai
The Evolution of Fluorescence Guided Surgery
A Wealth of Clinical Evidence
Over the years, the growing body of clinical evidence has solidified FGS as a critical tool in surgical
perfusion assessment, lymph node assessment, oncology and beyond. Studies have consistently
demonstrated that fluorescence guidance improves surgical outcomes by enhancing the surgeon’s
ability to identify and remove diseased tissue. For example, randomised controlled trials in breast
cancer surgery have shown that fluorescence imaging reduces the rate of positive margins, lowering
the need for reoperations. Similarly, in colorectal surgery, fluorescence-guided anastomosis has
been linked to a significant reduction in leak rates, a major source of postoperative complications.
Beyond oncology, FGS has found multiple applications in vascular surgery, organ transplantation,
and of course where it all started in ophthalmology. The versatility of this technology underscores
the profound impact of decades of research and clinical validation.
The Future: A Continuously Evolving Field
Looking ahead, the future of fluorescence-guided surgery is undeniably bright. The integration of
artificial intelligence and machine learning is expected to revolutionise how surgeons interpret
fluorescence signals, enabling real-time decision-making and predictive analytics.
Moreover, as the cost of imaging systems continues to decrease, FGS will become more accessible to
surgeons worldwide, including those in resource-limited settings. This democratisation of technology
will help close the gap in surgical outcomes between high- and low-income countries, further
cementing FGS as a global standard of care.
Conclusion
The journey of fluorescence-guided surgery from its humble beginnings in the 1950s to its current
status as a cornerstone of modern medicine is a testament to the power of scientific inquiry and
innovation. Over seven decades, researchers and clinicians have built a monumental body of
knowledge, transforming a nascent idea into a life-saving technology. As we look to the future, the
continued evolution of FGS, particularly through the synergy of ICG and artificial intelligence,
promises not only to improve surgical precision but also to redefine the boundaries of what is
possible in medicine.
