The ideal flap evaluation system would be non-invasive, assess large areas of skin, provide quantifiable data, and accurately distinguish between arterial and venous compromise in a timely fashion. No such system currently exists; however, our NIR fluorescence imaging system comes close to meeting these criteria. The greatest clinical benefit with our system is the ability to evaluate flaps in the operating room, with real-time overlay of flap physiology (i.e., using invisible NIR fluorescent light) with surgical anatomy (i.e., using color video). The portability of our system also permits its use in the post-operative setting when vascular compromise is suspected.
Currently, handheld Doppler is the most frequently used technique for flap monitoring.1
It is an easy monitoring device to use, while being inexpensive and non-invasive. A major limitation, however, is that it only evaluates a pinpoint site within the flap and may not distinguish global perfusion problems. In addition, it is difficult to quantify and to compare data. Newer methods of flap monitoring such as tissue oximetry (ViOptix, Fremont, CA) have attempted to eliminate the subjective nature of flap assessment. Tissue oximetry provides continuous monitoring that is quantifiable. This technique, however, is a poor evaluator of global perfusion as it provides data for a 1 cm area below the probe. In addition, the quantitative criteria for vascular compromise are still being established.
Our NIR imaging system can identify and quantify normal flap perfusion curves based on fluorescence intensity. More importantly, by comparing injections prior to flap elevation and after flap elevation, we were able to distinguish arterial and venous compromise with defined DR and TR values. We set 86% and 200% as the lower limit of the normal range for DR and TR, respectively, as these two values provided the highest accuracy. Using the diagnostic algorithm described in , 27% of our 190 post-operative evaluations had an abnormal DR and venous congestion. In contrast, 4.5% had an abnormal TR, which represents arterial spasm. The ultimate fate of flaps with such abnormalities is now being investigated.
We also compared the DR before and after flap elevation (p < 0.0001). The higher DR in post-operative evaluations most likely represents a redistribution of venous outflow seen in normal flap physiology. While the higher DR did not result ultimately in flap congestion, it may explain how early skin color changes after flap elevation such as hyperemia or rapid capillary refill can resolve and not manifest as flap failure. We are currently designing long-term survival studies to examine improvements in flap physiology.
NIR fluorescence angiography can also identify flaps with both arterial and venous compromise. Epinephrine induces both arterial and venous spasm non-selectively with local application, and all 9 injections after epinephrine irrigation resulted in epinephrine induces-spasm patterns that exceeded DR and TR thresholds. As for DR, the difference between spasm and venous occlusion patterns was significant, while venous occlusion and epinephrine induced-spasm were comparable. The difference in TR between spasm and epinephrine induced-spasm patterns was not significant. These results are consistent as spasm induced by epinephrine and surgical dissection is similar.
Previously reported NIR fluorescence angiography studies validated the clinical relevance of ICG fluorescence to tissue perfusion.20,21
At the time, it was found to be “too sensitive” for clinical use.22,23
Krishnan et al. suggested that flaps could potentially heal uneventfully even after NIR fluorescence angiography demonstrated signs of venous congestion.23
The study included only 9 patients, and leeches were applied to 2 patients with delayed clearance of ICG. There are many differences between the data from the Krishnan study and the data obtained during our study. Most importantly, their normal fluorescence curve lacked an obvious inflow peak, reaching a maximum level at 2 min that begins to fall between 8 and 10 min. The imaging device employed in that study may not have had the temporal responsivity and spatial sensitivity to capture peak arterial inflow. It is interesting that a similar CBR curve can be found utilizing our NIR imaging system when the region of interest is created away from the perforating artery. Presently, we have not determined the minimal CBR level for effective perfusion, and a long-term survival study is now underway.
Indocyanine green has been approved for medical use since 1956 and widely used for various diagnostic purposes. The incidence of severe adverse reactions with intravenous administration of ICG is extremely rare with reported rates between 0.00007 and 0.05%. There are no data available describing overdose in humans; however the LD50 of ICG in rabbits is reported at 50 to 80 mg/kg. The mean dose and concentration we used per injection was 2.5 mg (0.07 mg/kg), and the theoretical dose per injection for use in a 70 kg adult is approximately 5 mg. The required dose per injection is several hundreds times smaller than the LD50 in a rabbit, thus we believe the risk of ICG administration is minimal. None of the animals had clinical signs of an adverse reaction due to ICG administration in our study.
A limitation of our study is that we evaluated perfusion after flap creation with no microvascular transfer. This endpoint was chosen to facilitate collection of the large amounts of data necessary for flap assessment. Isolation and clamping of the artery and vein were performed to simulate vascular occlusion and flap failure; however, this may not properly approximate thrombus formation. Ideally, a microsurgical transfer would be performed to provide the most accurate clinical correlation and these studies are currently underway.