Abstract
For more information, please visit our website.
Background Fluorescein and indocyanine green (ICG) angiography are both useful in the diagnosis and treatment of many retinal diseases. In some cases, both tests must be performed for diagnosis and treatment; however, performing both is time-consuming and may require multiple injections.
Methods We designed a compact digital confocal scanning laser ophthalmoscope to perform true simultaneous fluorescein and ICG angiography. We report our experience using the instrument to perform 169 angiograms in 117 patients.
Results There were no unexpected adverse effects from mixing the dyes and administering them in 1 injection. An entire examination, including fundus photography, fluorescein angiography, and ICG angiography, could be performed in 45 minutes. It was possible to study differences in fluorescein patterns by comparing identically timed frames and to find cases in which ICG or fluorescein was optimal in visualizing retinal and subretinal structures. Confocal optical sections in the depth (z) dimension allowed viewing in different planes. It was possible to overlay ICG and fluorescein images or compare them side-by-side using a linked cursor. Digital transmission of the images was also performed.
Conclusions Simultaneous ICG and fluorescein angiography can be performed rapidly, safely, and conveniently. The availability of simultaneous angiography will allow critical determination of the relative advantages and disadvantages of both types of angiography.
FLUORESCEIN angiography is a useful tool for the diagnosis of many retinal diseases. It provides diagnostic as well as treatment information by allowing visualization of the retinal and choroidal vasculature. Angiography allows identification of leakage of the small fluorescein molecule in pathological states. More recently, indocyanine green (ICG) angiography has been developed. This molecule is larger (molecular weight, 775 d vs 332 d for fluorescein) and more protein-bound in plasma than is fluorescein and fluoresces in the infrared spectrum. Initially, ICG angiography was performed with infrared photographic film. However, the poor sensitivity of film coupled with the relatively weak fluorescence properties of the dye caused this method to be abandoned.1-3 The strong binding of ICG dye to plasma proteins results in slow leakage as compared with fluorescein and reduces the amount of extravascular fluorescence available for imaging. Digital video cameras have been used to capture images for ICG angiography. This has made ICG angiography a useful clinical diagnostic tool, particularly for imaging of subretinal neovascular membranes in cases where such membranes can not be adequately imaged with fluorescein angiography.4-8
Another approach to fluorescence angiography (using either fluorescein or ICG) is the scanning laser ophthalmoscope.9 This instrument has come into common clinical practice because of its commercialization in recent years.10 Advantages of the scanning laser ophthalmoscope include the ability to use an excitation light that scans the retina, allowing more intense excitation (thus providing a stronger emission signal) while still using safe levels of illumination. This is possible because the scanning beam illuminates each area point of the retina for only 0.1 to 0.7 microseconds. Scanning laser ophthalmoscope angiography gives temporal information that is richer than still ("digital") imaging systems because true video allows imaging at rates of 20 to 30 frames per second. This allows more detail to be seen in the transit phases and may give better information about patterns of leaking vessels. Furthermore, the illuminating beam is monochromatic and the intensity of fluorescence may be higher because of the scanning laser ophthalmoscope beam and the fact that point-by-point illumination is used.10 Stereoscopic imaging is also possible using scanning laser ophthalmoscope techniques.11
We recently described the use of a confocal scanning laser ophthalmoscope to perform tomographic imaging of macular diseases.12 By optically isolating the image plane to a narrow plane in the depth (z) dimension, depth information and measurements could be obtained. Subsequently, we adapted the scanning laser tomograph to perform ICG angiography.13,14 The instrument allowed better discrimination against out-of-focus objects (tomography) and provided higher contrast than other systems. The simple optical path and optimized excitation and emission detection systems improved the sensitivity of the instrument so that 70% of the photons exiting the eye could be detected. This allowed excellent visualization of vessels in the late stages (45 minutes) of the ICG angiogram without the use of a second ("landmark") injection of ICG dye.5 This instrument was the first completely digital instrument to allow scanning laser video angiography. Image capture and processing is done digitally so that no information is lost at any stage of processing, image manipulation, or transmission.
Although ICG angiography may be advantageous in certain cases of subretinal neovascularization and in diagnosing other disorders,4,5,7 one of its drawbacks is the long period of time required for angiography (45 minutes) and the need to obtain a second angiogram after a fluorescein angiogram is obtained. The process of obtaining a fluorescein and ICG angiogram sequentially is time consuming and requires 2 or 3 (if a landmark injection is used) injections for each patient for completion of the set of studies. Moreover, the angiograms are performed at different times, making it difficult to know if differences in fluorescence leakage patterns are due to differences in properties of the dyes or in the quality of the photographs. This may be one reason why different investigators vary in their assessment of the additional incremental benefit of ICG over fluorescein angiography.4,10,14-16 To determine if high-quality simultaneous images from fluorescein and ICG angiograms could be obtained, we modified a small, digital, personal computer–based confocal scanning laser ophthalmoscope to allow simultaneous imaging after a single intravenous injection of both ICG and fluorescein. We do not advocate performing simultaneous angiography on every patient; rather, our goal was to determine whether such angiography could be performed and to evaluate the characteristics of confocal simultaneous angiography.
Materials and methods
We used a confocal scanning laser ophthalmoscope with 2 laser light sources to illuminate the retina (Heidelberg Retina Angiograph, Heidelberg Engineering Inc, Carlsbad, Calif). The instrument uses 2 lasers with 3 wavelengths as light sources for scanning fundus illumination. An argon-ion laser (488 nm and 514 nm wavelength) was used to provide red-free photographs (green, 514 nm) and blue light was used for excitation during fluorescein angiograms (blue, 488 nm). The second laser was a diode laser (795 nm wavelength) that provided illumination to excite the ICG dye, which fluoresces at 835 nm. The instrument was operated in a tight confocal imaging mode and acquired up to 12 simultaneous frame pairs per second. For each video line of the angiogram, the forward scan was used for one angiogram and the backward scan was used for the other angiogram. Thus, the time separation between corresponding lines of the 2 angiograms was on the order of 0.1 milliseconds; each frame pair was acquired in 0.08 seconds. The instrument allowed acquisition of 12 frame pairs per second with 256 × 256 pixel and 8 bit per pixel intensity quantitation.
The images were recorded in the confocal mode12,16-18 while the photographer moved the plane of focus in the depth (z) dimension during the angiogram to optimally image the structures of interest. The chromatic aberration of the human eye caused a 1-diopter (D) focus shift between the blue-green fluorescein angiogram image plane and the infrared ICG angiogram image plane. The photographer selected a focal plane that allowed in-focus imaging of the retinal vasculature in the fluorescein angiogram, which placed the ICG image plane 300 µm deeper in the retina and choroid.
Patient examinations
We performed 169 angiograms in 117 patients with age-related macular degeneration, ocular melanoma, and other retinal diseases. The patients were studied after a complete ophthalmic examination that included fundus photography, slitlamp examination, and indirect ophthalmoscopy. We injected 2 mL of a mixture of 25 mg of ICG and 500 mg of sodium fluorescein intravenously. This was prepared using sterile commercially available dyes suitable for intravenous injection. The liquid sodium fluorescein (25% solution in 2 mL; Fluorescite, Alcon, Fort Worth, Tex) was placed into a vial containing sterile ICG powder (CardioGreen, Becton Dickinson, Cockeyville, Md) and the ICG was dissolved in the liquid fluorescein. No precipitates were seen. This resulted in a sterile solution containing 25 mg of ICG and 500 mg of sodium fluorescein. The patients underwent imaging in the early phase (0-2 minutes after injection), the mid phase (3-5 minutes for sodium fluorescein, 3-15 minutes for ICG), and late phase (10-12 minutes for sodium fluorescein, 40-45 minutes for ICG). All patients were informed as to the risk and benefit factors of all procedures. The images were analyzed by 2 ophthalmologists (W.R.F. and A.J.M.).
Image storage and retrieval
The images were stored digitally in the RAM of the computer during acquisition and subsequently transferred onto the hard disk. The still frames of a typical angiogram sequence (n=50 frames) required 3.2 megabytes of hard disk memory. Video sequences (20 frames per second) required 13 megabytes for each 10-second sequence of video. Using 40 megabytes of RAM, we allowed 30 seconds of live video storage before moving the data to permanent hard disk storage.
Results
Clinical advantages
One hundred sixty-nine angiograms were performed with no serious adverse reactions. Preparation of the dye mixture from the 2 commercially available sterile preparations was performed without problems. A saline solution "flush" injection was not necessary to obtain good image quality. The time necessary for an entire study was 45 minutes and only 1 injection per patient was needed. Red-free color images were also obtained using the green wavelength of the argon laser. Infared fundus photographs were obtained using the diode laser. It was not necessary to reinject ICG dye to image retinal vessels in the late phase of the study. The retinal vessels were visible at the 40-minute time point owing to the sensitivity of the detector, which allowed visualization of the background choroidal ICG dye fluorescence. This allowed imaging of the retinal vessels as dark linear structures silhouetted by this background fluorescence13 (Figure 1).
Time course of appearance of both dyes
Analysis of patients in whom rapid sequences of early frames were performed showed that the transit of ICG and fluorescein to the eye appeared to be simultaneous. This was best seen in the early laminar flow or arterial filling phases where arterial filling or localized venous laminar flow patterns could be seen. In these cases, the patterns of vascular filling over time appeared to be the same with both dyes (Figure 2). We found that it was possible to artificially make either dye appear to fluoresce earlier by changing the gain settings on the instrument. We did not perform absolute calibration of the emitted light from each point on the fundus. We found that it was easy to study the differences in fluorescence patterns, lesion localization, and leakage patterns using ICG and fluorescein with the simultaneously acquired images (Figure 2).
Clinical utility in subretinal neovascularization and other diseases
The production of true simultaneous images negated the possibility that one of the angiograms was of higher quality than the other and that this allowed better visualization of pathological states. The potential reasons that one study might be of better quality include better centering of the camera image pathway in the pupil, less patient movement, better focus, more correct exposure, less blinking, and other factors. Using the simultaneous angiogram, in some cases ICG showed a subretinal neovascular membrane better than fluorescein and in other cases fluorescein showed it better than ICG (Figure 3). Only a larger study can determine the relative sensitivity and specificity of the 2 techniques. Our review of the images suggests that both studies are needed in difficult cases. It is interesting that in some cases, feeder vessels can be seen in ICG and not in fluorescein angiogram frames (Figure 4).
We found that the ability to view multiple images or video-rate images provided more information than single frames. A pseudostereo image was possible by slowly moving the instrument in the horizontal meridian.11 The information density included horizontal resolution and a temporal component. During the study, frames were selectively focused at different planes because of the confocal nature of the detection system. The ability to procure images at rapid rates allowed us to select the most optimal frame for determining and guiding treatment.
Confocality
The use of confocal optics had 2 effects. It allowed imaging in a relatively narrow plane of focus and it also increased the contrast considerably. This improved the quality of the images.13 In addition, the ability to move the plane of focus in depth allowed the physician to discern the optimal plane of focus for visualizing the pathological structures of interest. As previously described,13 the higher contrast of this system allowed visualization of the retinal vasculature superimposed on the background ICG fluorescence in 40-minute late frames of the ICG angiograms (Figure 1). In addition, we were able to show the depth location of subretinal neovascular membranes by scanning at different planes of focus (Figure 5).
Registration and comparison of simultaneous images
We studied 2 methods for comparing the simultaneous ICG and fluorescein images. Color-coding the images (fluorescein in green and ICG in red) allowed overlay of the 2 images (Figure 6). We also were able to study the 2 monochromatic gray-scaled images side by side, electronically linked with a cursor. The cursor location in the 2 images always corresponded to the identical location in the fundus. This allowed simultaneous viewing of a given point on the fundus in both ICG and fluorescein images (Figure 7). We found this less confusing and more precise than the dual-color method. This method was possible only because each line of the angiogram was scanned both for ICG and fluorescein images in a quasi-simultaneous fashion and corresponding points could be determined. There was no image manipulation involved in performing this electronic linking between the 2 images.
Image storage, transfer, and retrieval
The output of the instrument was digital. Thus each image entailed 256 × 256 bytes plus 8-bit gray-scale information at each location. Each location of the fundus was imaged twice so that each image pair (ICG and fluorescein) was approximately 130 kilobytes. The completely digital nature of the output allowed storage of all of the acquired information electronically without any loss of detail. The images could be stored using the software designed for the instrument or could be loaded into any commercially available software on any platform, either PC or Macintosh. Several selected pairs of images could be easily transported on a single floppy disk to a second computer in a laser treatment room. We also were able to transport images via Internet connections (approximately 5 seconds per image pair) to remote sites anywhere in the world. Video information was stored on portable hard disk drives and a variety of other media at low cost. At our institution, we chose to use Ethernet cable to transport image pairs at times of approximately 1 second per ICG/fluorescein pair from the angiography suite to the laser suite.
Red-free photographs were also obtained with the green 514.5-nm channel of the argon laser and infrared photographs were procured with the diode laser wavelength. These showed subretinal structures such as drusen more clearly then color or red-free fundus photographs.19
These photographic images were not simultaneous but were taken at the same magnification and were suitable for performing overlays on angiographic images, as are used in posttreatment assessment in eyes treated for subretinal neovascularization.9,20 Infrared fundus photographs could also be performed with the instrument.
Comment
Simultaneous confocal ICG and fluorescein angiography using a confocal scanning laser ophthalmoscope has several advantages. Clinically, we noted no serious adverse reactions in a series of 169 simultaneous ICG/fluorescein injections. The time required to perform the entire study was considerably shorter than first performing a fluorescein study, reviewing it, and subsequently performing the ICG study. In addition, the confocal nature of the instrument allowed for extremely high contrast in the later images, which allowed visualization of retinal vessels at the late time points and obviated the need for a landmark injection of fluorescein. Thus, simultaneous angiography is beneficial both from the patient's perspective as well as that of the ophthalmologist's office staff; only 1 injection is needed and in 40 minutes fundus photography, ICG angiography, and fluorescein angiography can be completed and reviewed to diagnose and guide treatment. In general, we performed simultaneous angiography in cases in which prior fluorescein angiography did not or was not expected to reveal sufficient information for treatment or diagnosis. A saline solution flush injection was not used as high-quality images were obtained without it.
The ability to perform simultaneous angiography was demonstrated by Bischoff et al,21 who described a prototype simultaneous ICG and fluorescein angiogram based on a scanning laser ophthalmoscope. Their instrument differed from the instrument we describe. Their instrument acquired true simultaneous images of the fundus with 2 continuous laser light sources and 2 light detectors. It was a prototype and required the presence of a complicated computer setup, 2 video recorders, and 2 monitors, filling half a room. The set-up of the instrument in our study switches laser light sources during the acquisition of a single video line to capture quasi-simultaneous images (time separation, 0.1 milliseconds). The light exposure is limited as sources are never simultaneously active during the scan. In addition, the present instrument allows acquisition of red-free and infrared fundus photographs, as well as storing all images digitally so that any image can be recalled or transported at any time or location without any loss of image quality. The use of a PC computer platform allows the use of any software system and great flexibility in image storage and processing. It is important to realize that information density not only includes horizontal resolution but also a time component. By shifting planes of focus and angle of imaging, one can often see better details of the structure of interest and can also choose the individual frame that best shows the pathological feature of interest or the one that must be projected to guide laser therapy. Other advantages of video imaging include the ability to see moving particles in the fluorescein images; this may enhance the visualization of subretinal neovascular membranes.22
There has been some controversy regarding the issue of transit times of the 2 fluorescent dyes.21,22 We found both dyes arrived simultaneously in the early phase of our study. There is no reason for the dyes to arrive at different time points.23,24 When the relative gains of our detectors were equal, there was no evidence that one of the dyes transited faster than the other.
We found that it was easy to study the differences in fluorescence patterns and lesion localization using ICG and fluorescein with the simultaneously acquired images. We preferred the linked cursor software mode to critically and simultaneously compare locations of the ICG and fluorescein images. Color-coding of the 2 images with display of both images simultaneously could also be performed. We recognize that treatment based on ICG fluorescence has not been studied in randomized clinical trials. Clearly this is necessary, but the ability to obtain both studies simultaneously should be advantageous in designing such a trial. Using simultaneous angiography is the only way to determine the relative value of each type of angiography. Only through a large study of patients with a variety of retinal diseases using simultaneous ICG and fluorescein angiography will it be possible to critically determine the differences in vascular imaging and leakage patterns and their clinical significance.25 We do not advocate the use of simultaneous angiography for all patients. However, in those patients in whom conventional fluorescein angiography does not allow a conclusive analysis, simultaneous angiography seems to offer additional insight.
Accepted for publication November 26, 1997.
Supported by a grant from the Stern Foundation, La Jolla, Calif (Dr Freeman), the Whitaker Foundation, Rosslyn, Va (Dr Bartsch), and Deutsche Forschungsgemeinschaft, Bonn, Germany (Dr Mueller).
Reprints: William R. Freeman, MD, UCSD Shiley Eye Center, 9415 Campus Point Dr, La Jolla, CA 92093-0946.
References
Video 1 The angiography shows general hypoperfusion of the mastectomy skin flaps due to the use of Klein’s fluid for hydrodissection resulting in vasoconstriction.
Video 2 Indocyanine green angiography (ICG-A) showing hypoperfused areas (<33%) of the mastectomy flap after insertion of sizer before prepectoral breast reconstruction with implant and acellular dermal matrix (ADM).
Video 3 Indocyanine green angiography (ICG-A) showing sufficient perfusion after pre-pectoral breast reconstruction with implant and acellular dermal matrix (ADM).
Video 4 Indocyanine green angiography (ICG-A) after raising the lateral intercostal artery perforator (LICAP). Angiography visualizes perforators entering the flap.
Video 5 Intraoperative angiography confirms perforators entering the flap.
weiqing Product Page
Video 6 Per-operative indocyanine green angiography (ICG-A) on donor-site/abdominal region visualizing insufficient perfusion of the right side of the deep inferior epigastric artery perforator (DIEP)-flap.
Video 7 Indocyanine green angiography (ICG-A) showing insufficient intra-flap perfusion of a deep inferior epigastric artery perforator (DIEP)-flap after transposition to the breast region and microvascular anastomoses. Patient experienced partial flap loss of the medial 20% of the flap corresponding to the intraoperative angiography.
An increasing number of women seek a breast reconstruction, due to increased survival rate after breast cancer (1). A breast reconstruction aims to increase the quality of life and obtain a new breast with an acceptable size, shape and symmetry (2-5). Sufficient perfusion is important in achieving a successful implant-based, oncoplastic- or autologous breast reconstruction. Indocyanine green angiography (ICG-A) is an intraoperative imaging modality visualizing blood flow to the tissue of interest (6-8). The real-time assessment of perfusion supports the surgeon in intraoperative decision making, which consequently leads to a decreased risk of postoperative complications and loss of reconstruction (9-16). We present the following article in accordance with the Narrative Review reporting checklist (available at https://abs.amegroups.com/article/view/10.21037/abs-21-25/rc).
ICG-A has been used to assess skin perfusion for the last two decades (17-19) and is a widely used and well described imaging technique for evaluating tissue perfusion (6,8,20). The modality is not only used to asses arterial perfusion, but has also been described for evaluation of microvascular anastomoses (21,22), venous congestion (23,24), augmentation mastopexy (25), breast reduction surgery (26) and investigation of perfusion zones (27-31).
Scoring and cut-off values in terms of sensitivity, specificity, positive predictive- and negative predictive values have been investigated by several authors (10,11,32-37). In mastectomy flaps, ICG-A has been reported with a sensitivity of 90% and specificity of 100% in reducing skin flap necrosis and overall complication rate (10,38-40). Moyer et al. suggested a cut-off perfusion score of 33% in preventing mastectomy flap necrosis (33). In autologous breast reconstruction establishment of a specific cut-off value and perfusion assessment have yet to be determined (15,41-45).
The majority of published studies on ICG-A in breast reconstruction are of lower level of evidence and consists of comparative, case and cohort studies. Only one randomized controlled trial (RCT)-study investigating ICG-A is published (15). The study investigated the use of ICG-A in deep inferior epigastric artery perforator (DIEP)-flaps and found a significant decreased incidence of fat necrosis (15).
A systematic review from 2020 on the use of ICG-A in autologous breast reconstruction, concluded that per-operative perfusion assessment by ICG-A was an effective tool in reducing fat necrosis compared with flaps assessed clinically (46). Mastectomy skin flap necrosis and the risk of repeated surgeries were reported significantly decreased in 2 reviews and 1 meta-analysis (36,37,47). A Cochrane review on ICG-A on mastectomy skin flap perfusion in immediate breast reconstructions was inconclusive due to lack of high-quality evidence (48). Johnson et al. investigated the overall use of ICG-A in breast reconstructions, and reported a reduced postoperative tissue loss when applying ICG-A, but emphasized the need for standardization (35).
In the following we present a narrative review and a description on how ICG-A may be used in implant-based, oncoplastic- and autologous breast reconstruction demonstrated by clinical examples.
ICG-A offers an objective, repeatable and real-time imaging of the vascularity and perfusion of tissue (7,49). Indocyanine green (ICG) is a water-soluble molecule excreted via the liver to the bile. The technique is repeatable due to a short half-life of 3–5 minutes. Upon intravenous injection of ICG during surgery a fluorescent near-infrared camera detects the molecule and visualizes perfusion within approximately 20 seconds (6). There is up until now no consensus on the intraoperative dose of ICG which is reported from 2 up to 250 mg (13,50,51).
Several imaging-systems exists among others the Fluobeam Clinical System® (Fluoptics, Grenoble, France, www.fluoptics.com), HyperEye Medical Systems® (Mizuho, Tokyo, Japan, www.mizuhomedical.co.jp) and IC-View® Pulsion Medical Systems. One of the most commonly used systems is the Spy-Elite Fluorescence Imaging Systemâ which is able to quantify perfusion and apply relative values of blood flow in the tissue (33,52). Wearable technology in the form of smart glasses have also been described (53).
Patients undergoing breast reconstruction should be informed of the rationale and use of per-operative ICG-A. Potential side-effects such as nausea, dizziness, discomfort, rash and sweating occur in up to 0.2–0.34%, and is thoroughly discussed with the patient (32,54-56). Patients allergic to iodine should be excluded due to risk of anaphylaxis (51).
The incidence of anaphylactic shock is rare, and occurs in approximately 1 in 42,000 patients (56). Also, though extravasation is rare, extravasation of ICG may cause reversible discoloration of the skin (Figure 1).
Figure 1 Patient with discoloration of the leg after extravasation of indocyanine green used per-operatively. The color diminished gradually within 3 months leaving no sequelae.
Mastectomy, being it nipple-sparing or skin-sparing, is performed in the plane of the subcutaneous fascia to preserve the dermal blood supply. Hemostasis is secured using bipolar diathermia. After removal of the breast tissue, the surgeon evaluates the skin flaps estimating areas in risk of potential hypoperfusion. The breast surgeon should refrain from using vasoconstrictive agents such as Klein’s fluid (Ringer lactate, lidocaine and adrenaline) to avoid distortion of the assessment of the ICG-A (Figure 2).
Figure 2 ICG-A performed on mastectomy flaps after a skin-sparing subcutaneous mastectomy using vasoconstrictive agents. (A) The angiography shows general hypoperfusion of the mastectomy skin flaps due to the use of Klein’s fluid for hydrodissection resulting in vasoconstriction (®, perfusion is <5%. (C) ICG-A color mode showed hypoperfusion indicated by the dark blue color. (D) Per-operative clinical photo of the mastectomy flaps. The patients right side mastectomy flaps are thin and discolored due to the use of vasoconstrictive agents for the hydrodissection during mastectomy. ICG-A, indocyanine green angiography.ICG-A performed on mastectomy flaps after a skin-sparing subcutaneous mastectomy using vasoconstrictive agents. (A) The angiography shows general hypoperfusion of the mastectomy skin flaps due to the use of Klein’s fluid for hydrodissection resulting in vasoconstriction ( Video 1 ). (B) Scoring perfusion by the Spy-Elite Fluorescence Imaging System, perfusion is <5%. (C) ICG-A color mode showed hypoperfusion indicated by the dark blue color. (D) Per-operative clinical photo of the mastectomy flaps. The patients right side mastectomy flaps are thin and discolored due to the use of vasoconstrictive agents for the hydrodissection during mastectomy. ICG-A, indocyanine green angiography.
A sizer of appropriate size is inserted, and dermis is sutured temporarily. Twenty-five milligrams of ICG are diluted in 10 mL sterile water, an intravenous bolus administration of ICG (Verdyeâ 5 mg/mL) of 2.5 mg/mL is followed by a 10 mL flush with normal saline (2.5 mL of ICG solution for each administration).
The ICG is injected and the perfusion scored by the SPY-Eliteâ system. A perfusion below 33% may lead to reevaluation of the reconstructive procedure by reducing volume of the sizer to eliminate the skin tension (33).
In cases with perfusion below 33% on the first ICG-A, the technique is repeated and re-evaluated using the same dose of ICG, after 20 minutes (6). Consequently, a perfusion <33% on the 2. angiography will result in excision of the hypoperfused area (if located near incision area), a smaller implant or result in reconstruction with subpectoral placement of a tissue expander (TE) (Figure 3).
Figure 3 A case where the surgeon chose not to excise the hypoperfused areas indicated by the ICG-A. (A) ICG-A showing hypoperfused areas (<33%) of the mastectomy flap after insertion of sizer before prepectoral breast reconstruction with implant and ADM (® 5 days postoperatively, perfusion is centrally <33% corresponding to the clinic. NAC, nipple areola complex; ADM, acellular dermal matrix; ICG-A, indocyanine green angiography.A case where the surgeon chose not to excise the hypoperfused areas indicated by the ICG-A. (A) ICG-A showing hypoperfused areas (<33%) of the mastectomy flap after insertion of sizer before prepectoral breast reconstruction with implant and ADM ( Video 2 ). (B) Clinical photo. The patient developed epidermolysis and necrosis 5 days postoperatively corresponding to the ICG-A. The necrotic areas were excised, the implant extracted and the patient underwent 2-stage reconstruction with TE. (C) ICG-A color mode shows central hypoperfusion as seen on the ICG-A. (D) Scoring perfusion by the Spy-Elite Fluorescence Imaging System5 days postoperatively, perfusion is centrally <33% corresponding to the clinic. NAC, nipple areola complex; ADM, acellular dermal matrix; ICG-A, indocyanine green angiography.
In cases with sufficient perfusion, the reconstruction proceeds with either a pre-pectoral implant wrapped in acellular dermal matrix (ADM) or a subpectoral implant or TE.
After completing the breast reconstruction, ICG-A is then performed again to confirm and ensure sufficient perfusion (Figure 4).
Figure 4 Pre-pectoral breast reconstruction with implant and ADM. (A) ICG-A showing sufficient perfusion after pre-pectoral breast reconstruction with implant and ADM (®, perfusion is generally >33% and indicates sufficient perfusion to proceed with the planned reconstruction. (C) ICG-A color mode indicating sufficient perfusion. ADM, acellular dermal matrix; ICG-A, indocyanine green angiography.Pre-pectoral breast reconstruction with implant and ADM. (A) ICG-A showing sufficient perfusion after pre-pectoral breast reconstruction with implant and ADM ( Video 3 ). (B) Scoring perfusion by the Spy-Elite Fluorescence Imaging System, perfusion is generally >33% and indicates sufficient perfusion to proceed with the planned reconstruction. (C) ICG-A color mode indicating sufficient perfusion. ADM, acellular dermal matrix; ICG-A, indocyanine green angiography.
Oncoplastic techniques have been used for several decades and can be applied to achieve an acceptable aesthetic result after breast conserving therapy (57-59). Corrective techniques span from Z-plasties and local flaps to larger transposition, advancement and perforator flaps (57). The oncoplastic surgery aims to balance and restore the shape of the breast subsequent to oncologic resection (59). Reshaping and relocation of tissue can compromise perfusion and makes ICG-A a valuable tool in oncoplastic breast surgery (58).
After removing the cancer and intraoperative confirmation of adequate resection, the lateral intercostal artery perforator (LICAP) flap is raised to replace volume and reshape the breast (60). ICG-A can be used per-operatively to assess and score perfusion before after raising the flap, after advancement and before wound closure (Figure 5). In oncoplastic displacement (e.g., breast reduction oncoplasty), the ICG-A technique is used as described for the displacement techniques.
Figure 5 Assessment and scoring of perfusion of LICAP-flap before the flap was deepithelialized and advanced in to the breast. (A) ICG-A after raising the LICAP. Angiography visualizes perforators entering the flap (Assessment and scoring of perfusion of LICAP-flap before the flap was deepithelialized and advanced in to the breast. (A) ICG-A after raising the LICAP. Angiography visualizes perforators entering the flap ( Video 4 ). (B) Quantification and scoring of perfusion shows sufficient perfusion of the entire flap. (C) ICG-A color mode with sufficient perfusion. (D) Clinical photo of the LICAP-flap before the flap was deepithelialized and advanced in to the breast. ICG-A, indocyanine green angiography; LICAP, lateral intercostal artery perforator.
Preoperatively a doppler ultrasonography can be used to mark the perforators or artery(ies) if the chosen pedicled flap is a muscle sparing latissimus dorsi (msLD) or a thoracodorsal artery perforator flap (TAP). Perfusion of the flap can then be scored by ICG-A [as described (33)] performed after incision around the flap to the fascia. The angiography indicates the number of perforators within the flap (Figure 6).
Figure 6 Per-operative ICG-A of a LD-flap after incision around the flap, before flap is elevated on the pedicle. The angiography visualizes the perforators entering the flap. Scoring of perfusion by the Spy-Elite Fluorescence Imaging System®. (A) Intraoperative angiography confirms perforators entering the flap (Per-operative ICG-A of a LD-flap after incision around the flap, before flap is elevated on the pedicle. The angiography visualizes the perforators entering the flap. Scoring of perfusion by the Spy-Elite Fluorescence Imaging System. (A) Intraoperative angiography confirms perforators entering the flap ( Video 5 ). (B) Quantification and scoring of perfusion shows sufficient perfusion of the entire flap. (C) ICG-A color mode visualizes perforators and perfusion. ICG-A, indocyanine green angiography; LD, latissimus dorsi.
We recommend repeating ICG-A after the flap is completely raised on its pedicle—before transposition/advancement—which allows assessment of the chosen perforator or artery in order to evaluate possible changes in perfusion—assessing the angiosome if the flap is designed as a perforator flap. The final angiography is performed after the flap is transposed to the recipient site. Areas with hypoperfusion (<33%) should be excised.
The angiographies can aid the surgeon in the intraoperative surgical decision making, and the perfusion measurement may identify areas in risk of postoperative necrosis due to hypoperfusion (Figure 7).
Figure 7 Delayed breast reconstruction using a msLD flap combined with a tissue expander. (A) Intraoperative ICG-A showed hypoperfusion (<33%) of the medial part of the flap, but the area was not excised. (B) Demarcation, epidermolysis and necrosis developed 2 days postoperatively at the medial part of the flap, corresponding to the per-operative ICG-A. (C) Take-back surgery with removal of TE and excision of necrotic tissue. (D) ICG-A confirmed sufficient perfusion and the patient healed uneventfully. Green numbers indicate the relative perfusion score. msLD, muscle sparing latissimus dorsi flap; ICG-A, indocyanine green angiography; TE, tissue expander.
For breast reconstruction using a free abdominal flap, e.g., deep inferior epigastric artery perforator flap (DIEP), superficial inferior epigastric artery (SIEA) or muscle sparring transverse rectus abdominis (msTRAM) flap, ICG-A can be used to evaluate perfusion of the flap, aiding flap design, identification of perforators and assessing perfusion zones, microvascular anastomoses, venous insufficiency etc.
A preoperative computed tomography angiography (CT-A) is done to identify the perforators and the intramuscular course of the vessels in the flap. By performing ICG-A (as described above) upon incision around the flap to the fascial level—before entering the subfascial plane—the complete number of perforators entering the flap can be identified and compared with the preoperative CT-A.
Based on this assessment, the best/most reliable perforators may be dissected, and the angiography repeated, allowing real-time assessment of the perfusion while aiding the intraoperative flap design. If the angiography indicates areas of insufficient perfusion, the surgeon is able to reevaluate and adjust the reconstructive procedure (Figure 8).
Figure 8 Planned breast reconstruction with bilateral DIEP-flap. ICG-A performed per-operatively at donor-site/abdominal region, after dissection of perforators before entering the abdominal subfascial plane, showed insufficient perfusion of the right half of the flap. The angiography aided the surgeon to reevaluate the reconstructive procedure. (A) Per-operative ICG-A on donor-site/abdominal region visualizing insufficient perfusion of the right side of the DIEP-flap (Planned breast reconstruction with bilateral DIEP-flap. ICG-A performed per-operatively at donor-site/abdominal region, after dissection of perforators before entering the abdominal subfascial plane, showed insufficient perfusion of the right half of the flap. The angiography aided the surgeon to reevaluate the reconstructive procedure. (A) Per-operative ICG-A on donor-site/abdominal region visualizing insufficient perfusion of the right side of the DIEP-flap ( Video 6 ). (B) Per-operative ICG-A. Scoring of the perfusion shows perfusion <33% on the right side of the flap. (C) ICG-A color mode depicts insufficient perfusion of the right side of the DIEP-flap. (D) Per-operative clinical photo. Area with insufficient perfusion is marked on the skin. ICG-A, indocyanine green angiography; DIEP, deep inferior epigastric artery perforator flap.
After the flap is raised with complete pedicle dissection, ICG-A is repeated allowing a final assessment of flap perfusion before transposition to the breast.
Upon completing the microvascular anastomoses, a repeated angiography may display possible hypoperfused areas of the flap, venous insufficiency or insufficient intra-flap perfusion (Figure 9).
Figure 9 Delayed breast reconstruction with a DIEP-flap (left breast). Pictures of the postoperative complications corresponding to intraoperative ICG-A. (A) ICG-A showing insufficient intra-flap perfusion of a DIEP-flap after transposition to the breast region and microvascular anastomoses. Patient experienced partial flap loss of the medial 20% of the flap corresponding to the intraoperative angiography (Delayed breast reconstruction with a DIEP-flap (left breast). Pictures of the postoperative complications corresponding to intraoperative ICG-A. (A) ICG-A showing insufficient intra-flap perfusion of a DIEP-flap after transposition to the breast region and microvascular anastomoses. Patient experienced partial flap loss of the medial 20% of the flap corresponding to the intraoperative angiography ( Video 7 ). (B) Two days postoperatively, clinical demarcation and epidermolysis of medial segment of the flap. (C) Eighteen days postoperatively, the necrosis of medial segment. (D) After secondary revision and excision of medial segment with necrosis, the patient healed with no further complications. ICG-A, indocyanine green angiography; DIEP, deep inferior epigastric artery perforator flap.
Using ICG-A intraoperatively informs the surgeon of possible insufficiently perfused areas of the flap and aids in reevaluating the breast reconstruction strategy to prevent postoperative complications.
A successful breast reconstruction requires sufficient blood perfusion preventing postoperative complications and loss of reconstruction.
ICG-A provides the surgeon with real-time accurate assessment of the tissue and intraoperative perfusion (7,49). Making information on real-time tissue perfusion available intraoperatively can assist the surgical decision making, providing the opportunity to reevaluate and adapt the reconstruction technique. Repeated intraoperative use of this imaging technique supplies valuable information on perfusion in every step of the reconstruction.
Surgical decision making often relies on clinical experience and judgement. ICG-A can assist the surgeon by providing real-time assessment, scoring and quantification of tissue perfusion.
The role of ICG-A in breast reconstructive procedures is not exhausted.
Determining cut-off values for perfusion, correlating these to postoperative fat necrosis rates or ultimately flap loss remains yet to be investigated. Moreover, further studies, exploring the role of ICG-A in postoperative monitoring, assessment of venous congestion and microvascular anastomoses may further expand the applications of ICG-A in breast reconstructive surgery.
We acknowledge Dr. Rami Mossad Ibrahim, MD. Department of Plastic Surgery and Burns Treatment, University Hospital Copenhagen for assisting the photo and video editing.
Funding: None.
Provenance and Peer Review: This article was commissioned by the editorial office, Annals of Breast Surgery for the series “Breast Reconstruction - The True Multidisciplinary Approach”. The article has undergone external peer review.
Reporting Checklist: The authors have completed the Narrative Review reporting checklist. Available at https://abs.amegroups.com/article/view/10.21037/abs-21-25/rc
Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://abs.amegroups.com/article/view/10.21037/abs-21-25/coif). The series “Breast Reconstruction - The True Multidisciplinary Approach” was commissioned by the editorial office without any funding or sponsorship. TED served as the unpaid Guest Editor of the series. The authors have no other conflicts of interest to declare.
Disclaimer: Videos and clinical photos published with this article are original. Copyright: Dr. Elisabeth Lauritzen, MD, PhD-student, Department of Plastic Surgery and Burns Treatment, University Hospital Copenhagen.
Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.
Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.
doi: 10.21037/abs-21-25
Cite this article as: Lauritzen E, Bredgaard R, Bonde C, Jensen LT, Damsgaard TE. Indocyanine green angiography in breast reconstruction: a narrative review. Ann Breast Surg 2022;6:6.
Abstract
Background Fluorescein and indocyanine green (ICG) angiography are both useful in the diagnosis and treatment of many retinal diseases. In some cases, both tests must be performed for diagnosis and treatment; however, performing both is time-consuming and may require multiple injections.
Methods We designed a compact digital confocal scanning laser ophthalmoscope to perform true simultaneous fluorescein and ICG angiography. We report our experience using the instrument to perform 169 angiograms in 117 patients.
Results There were no unexpected adverse effects from mixing the dyes and administering them in 1 injection. An entire examination, including fundus photography, fluorescein angiography, and ICG angiography, could be performed in 45 minutes. It was possible to study differences in fluorescein patterns by comparing identically timed frames and to find cases in which ICG or fluorescein was optimal in visualizing retinal and subretinal structures. Confocal optical sections in the depth (z) dimension allowed viewing in different planes. It was possible to overlay ICG and fluorescein images or compare them side-by-side using a linked cursor. Digital transmission of the images was also performed.
Conclusions Simultaneous ICG and fluorescein angiography can be performed rapidly, safely, and conveniently. The availability of simultaneous angiography will allow critical determination of the relative advantages and disadvantages of both types of angiography.
FLUORESCEIN angiography is a useful tool for the diagnosis of many retinal diseases. It provides diagnostic as well as treatment information by allowing visualization of the retinal and choroidal vasculature. Angiography allows identification of leakage of the small fluorescein molecule in pathological states. More recently, indocyanine green (ICG) angiography has been developed. This molecule is larger (molecular weight, 775 d vs 332 d for fluorescein) and more protein-bound in plasma than is fluorescein and fluoresces in the infrared spectrum. Initially, ICG angiography was performed with infrared photographic film. However, the poor sensitivity of film coupled with the relatively weak fluorescence properties of the dye caused this method to be abandoned.1-3 The strong binding of ICG dye to plasma proteins results in slow leakage as compared with fluorescein and reduces the amount of extravascular fluorescence available for imaging. Digital video cameras have been used to capture images for ICG angiography. This has made ICG angiography a useful clinical diagnostic tool, particularly for imaging of subretinal neovascular membranes in cases where such membranes can not be adequately imaged with fluorescein angiography.4-8
Another approach to fluorescence angiography (using either fluorescein or ICG) is the scanning laser ophthalmoscope.9 This instrument has come into common clinical practice because of its commercialization in recent years.10 Advantages of the scanning laser ophthalmoscope include the ability to use an excitation light that scans the retina, allowing more intense excitation (thus providing a stronger emission signal) while still using safe levels of illumination. This is possible because the scanning beam illuminates each area point of the retina for only 0.1 to 0.7 microseconds. Scanning laser ophthalmoscope angiography gives temporal information that is richer than still ("digital") imaging systems because true video allows imaging at rates of 20 to 30 frames per second. This allows more detail to be seen in the transit phases and may give better information about patterns of leaking vessels. Furthermore, the illuminating beam is monochromatic and the intensity of fluorescence may be higher because of the scanning laser ophthalmoscope beam and the fact that point-by-point illumination is used.10 Stereoscopic imaging is also possible using scanning laser ophthalmoscope techniques.11
We recently described the use of a confocal scanning laser ophthalmoscope to perform tomographic imaging of macular diseases.12 By optically isolating the image plane to a narrow plane in the depth (z) dimension, depth information and measurements could be obtained. Subsequently, we adapted the scanning laser tomograph to perform ICG angiography.13,14 The instrument allowed better discrimination against out-of-focus objects (tomography) and provided higher contrast than other systems. The simple optical path and optimized excitation and emission detection systems improved the sensitivity of the instrument so that 70% of the photons exiting the eye could be detected. This allowed excellent visualization of vessels in the late stages (45 minutes) of the ICG angiogram without the use of a second ("landmark") injection of ICG dye.5 This instrument was the first completely digital instrument to allow scanning laser video angiography. Image capture and processing is done digitally so that no information is lost at any stage of processing, image manipulation, or transmission.
Although ICG angiography may be advantageous in certain cases of subretinal neovascularization and in diagnosing other disorders,4,5,7 one of its drawbacks is the long period of time required for angiography (45 minutes) and the need to obtain a second angiogram after a fluorescein angiogram is obtained. The process of obtaining a fluorescein and ICG angiogram sequentially is time consuming and requires 2 or 3 (if a landmark injection is used) injections for each patient for completion of the set of studies. Moreover, the angiograms are performed at different times, making it difficult to know if differences in fluorescence leakage patterns are due to differences in properties of the dyes or in the quality of the photographs. This may be one reason why different investigators vary in their assessment of the additional incremental benefit of ICG over fluorescein angiography.4,10,14-16 To determine if high-quality simultaneous images from fluorescein and ICG angiograms could be obtained, we modified a small, digital, personal computer–based confocal scanning laser ophthalmoscope to allow simultaneous imaging after a single intravenous injection of both ICG and fluorescein. We do not advocate performing simultaneous angiography on every patient; rather, our goal was to determine whether such angiography could be performed and to evaluate the characteristics of confocal simultaneous angiography.
Materials and methods
We used a confocal scanning laser ophthalmoscope with 2 laser light sources to illuminate the retina (Heidelberg Retina Angiograph, Heidelberg Engineering Inc, Carlsbad, Calif). The instrument uses 2 lasers with 3 wavelengths as light sources for scanning fundus illumination. An argon-ion laser (488 nm and 514 nm wavelength) was used to provide red-free photographs (green, 514 nm) and blue light was used for excitation during fluorescein angiograms (blue, 488 nm). The second laser was a diode laser (795 nm wavelength) that provided illumination to excite the ICG dye, which fluoresces at 835 nm. The instrument was operated in a tight confocal imaging mode and acquired up to 12 simultaneous frame pairs per second. For each video line of the angiogram, the forward scan was used for one angiogram and the backward scan was used for the other angiogram. Thus, the time separation between corresponding lines of the 2 angiograms was on the order of 0.1 milliseconds; each frame pair was acquired in 0.08 seconds. The instrument allowed acquisition of 12 frame pairs per second with 256 × 256 pixel and 8 bit per pixel intensity quantitation.
The images were recorded in the confocal mode12,16-18 while the photographer moved the plane of focus in the depth (z) dimension during the angiogram to optimally image the structures of interest. The chromatic aberration of the human eye caused a 1-diopter (D) focus shift between the blue-green fluorescein angiogram image plane and the infrared ICG angiogram image plane. The photographer selected a focal plane that allowed in-focus imaging of the retinal vasculature in the fluorescein angiogram, which placed the ICG image plane 300 µm deeper in the retina and choroid.
Patient examinations
We performed 169 angiograms in 117 patients with age-related macular degeneration, ocular melanoma, and other retinal diseases. The patients were studied after a complete ophthalmic examination that included fundus photography, slitlamp examination, and indirect ophthalmoscopy. We injected 2 mL of a mixture of 25 mg of ICG and 500 mg of sodium fluorescein intravenously. This was prepared using sterile commercially available dyes suitable for intravenous injection. The liquid sodium fluorescein (25% solution in 2 mL; Fluorescite, Alcon, Fort Worth, Tex) was placed into a vial containing sterile ICG powder (CardioGreen, Becton Dickinson, Cockeyville, Md) and the ICG was dissolved in the liquid fluorescein. No precipitates were seen. This resulted in a sterile solution containing 25 mg of ICG and 500 mg of sodium fluorescein. The patients underwent imaging in the early phase (0-2 minutes after injection), the mid phase (3-5 minutes for sodium fluorescein, 3-15 minutes for ICG), and late phase (10-12 minutes for sodium fluorescein, 40-45 minutes for ICG). All patients were informed as to the risk and benefit factors of all procedures. The images were analyzed by 2 ophthalmologists (W.R.F. and A.J.M.).
Image storage and retrieval
The images were stored digitally in the RAM of the computer during acquisition and subsequently transferred onto the hard disk. The still frames of a typical angiogram sequence (n=50 frames) required 3.2 megabytes of hard disk memory. Video sequences (20 frames per second) required 13 megabytes for each 10-second sequence of video. Using 40 megabytes of RAM, we allowed 30 seconds of live video storage before moving the data to permanent hard disk storage.
Results
Clinical advantages
One hundred sixty-nine angiograms were performed with no serious adverse reactions. Preparation of the dye mixture from the 2 commercially available sterile preparations was performed without problems. A saline solution "flush" injection was not necessary to obtain good image quality. The time necessary for an entire study was 45 minutes and only 1 injection per patient was needed. Red-free color images were also obtained using the green wavelength of the argon laser. Infared fundus photographs were obtained using the diode laser. It was not necessary to reinject ICG dye to image retinal vessels in the late phase of the study. The retinal vessels were visible at the 40-minute time point owing to the sensitivity of the detector, which allowed visualization of the background choroidal ICG dye fluorescence. This allowed imaging of the retinal vessels as dark linear structures silhouetted by this background fluorescence13 (Figure 1).
Time course of appearance of both dyes
Analysis of patients in whom rapid sequences of early frames were performed showed that the transit of ICG and fluorescein to the eye appeared to be simultaneous. This was best seen in the early laminar flow or arterial filling phases where arterial filling or localized venous laminar flow patterns could be seen. In these cases, the patterns of vascular filling over time appeared to be the same with both dyes (Figure 2). We found that it was possible to artificially make either dye appear to fluoresce earlier by changing the gain settings on the instrument. We did not perform absolute calibration of the emitted light from each point on the fundus. We found that it was easy to study the differences in fluorescence patterns, lesion localization, and leakage patterns using ICG and fluorescein with the simultaneously acquired images (Figure 2).
Clinical utility in subretinal neovascularization and other diseases
The production of true simultaneous images negated the possibility that one of the angiograms was of higher quality than the other and that this allowed better visualization of pathological states. The potential reasons that one study might be of better quality include better centering of the camera image pathway in the pupil, less patient movement, better focus, more correct exposure, less blinking, and other factors. Using the simultaneous angiogram, in some cases ICG showed a subretinal neovascular membrane better than fluorescein and in other cases fluorescein showed it better than ICG (Figure 3). Only a larger study can determine the relative sensitivity and specificity of the 2 techniques. Our review of the images suggests that both studies are needed in difficult cases. It is interesting that in some cases, feeder vessels can be seen in ICG and not in fluorescein angiogram frames (Figure 4).
We found that the ability to view multiple images or video-rate images provided more information than single frames. A pseudostereo image was possible by slowly moving the instrument in the horizontal meridian.11 The information density included horizontal resolution and a temporal component. During the study, frames were selectively focused at different planes because of the confocal nature of the detection system. The ability to procure images at rapid rates allowed us to select the most optimal frame for determining and guiding treatment.
Confocality
The use of confocal optics had 2 effects. It allowed imaging in a relatively narrow plane of focus and it also increased the contrast considerably. This improved the quality of the images.13 In addition, the ability to move the plane of focus in depth allowed the physician to discern the optimal plane of focus for visualizing the pathological structures of interest. As previously described,13 the higher contrast of this system allowed visualization of the retinal vasculature superimposed on the background ICG fluorescence in 40-minute late frames of the ICG angiograms (Figure 1). In addition, we were able to show the depth location of subretinal neovascular membranes by scanning at different planes of focus (Figure 5).
Registration and comparison of simultaneous images
We studied 2 methods for comparing the simultaneous ICG and fluorescein images. Color-coding the images (fluorescein in green and ICG in red) allowed overlay of the 2 images (Figure 6). We also were able to study the 2 monochromatic gray-scaled images side by side, electronically linked with a cursor. The cursor location in the 2 images always corresponded to the identical location in the fundus. This allowed simultaneous viewing of a given point on the fundus in both ICG and fluorescein images (Figure 7). We found this less confusing and more precise than the dual-color method. This method was possible only because each line of the angiogram was scanned both for ICG and fluorescein images in a quasi-simultaneous fashion and corresponding points could be determined. There was no image manipulation involved in performing this electronic linking between the 2 images.
Image storage, transfer, and retrieval
The output of the instrument was digital. Thus each image entailed 256 × 256 bytes plus 8-bit gray-scale information at each location. Each location of the fundus was imaged twice so that each image pair (ICG and fluorescein) was approximately 130 kilobytes. The completely digital nature of the output allowed storage of all of the acquired information electronically without any loss of detail. The images could be stored using the software designed for the instrument or could be loaded into any commercially available software on any platform, either PC or Macintosh. Several selected pairs of images could be easily transported on a single floppy disk to a second computer in a laser treatment room. We also were able to transport images via Internet connections (approximately 5 seconds per image pair) to remote sites anywhere in the world. Video information was stored on portable hard disk drives and a variety of other media at low cost. At our institution, we chose to use Ethernet cable to transport image pairs at times of approximately 1 second per ICG/fluorescein pair from the angiography suite to the laser suite.
Red-free photographs were also obtained with the green 514.5-nm channel of the argon laser and infrared photographs were procured with the diode laser wavelength. These showed subretinal structures such as drusen more clearly then color or red-free fundus photographs.19
These photographic images were not simultaneous but were taken at the same magnification and were suitable for performing overlays on angiographic images, as are used in posttreatment assessment in eyes treated for subretinal neovascularization.9,20 Infrared fundus photographs could also be performed with the instrument.
Comment
Simultaneous confocal ICG and fluorescein angiography using a confocal scanning laser ophthalmoscope has several advantages. Clinically, we noted no serious adverse reactions in a series of 169 simultaneous ICG/fluorescein injections. The time required to perform the entire study was considerably shorter than first performing a fluorescein study, reviewing it, and subsequently performing the ICG study. In addition, the confocal nature of the instrument allowed for extremely high contrast in the later images, which allowed visualization of retinal vessels at the late time points and obviated the need for a landmark injection of fluorescein. Thus, simultaneous angiography is beneficial both from the patient's perspective as well as that of the ophthalmologist's office staff; only 1 injection is needed and in 40 minutes fundus photography, ICG angiography, and fluorescein angiography can be completed and reviewed to diagnose and guide treatment. In general, we performed simultaneous angiography in cases in which prior fluorescein angiography did not or was not expected to reveal sufficient information for treatment or diagnosis. A saline solution flush injection was not used as high-quality images were obtained without it.
The ability to perform simultaneous angiography was demonstrated by Bischoff et al,21 who described a prototype simultaneous ICG and fluorescein angiogram based on a scanning laser ophthalmoscope. Their instrument differed from the instrument we describe. Their instrument acquired true simultaneous images of the fundus with 2 continuous laser light sources and 2 light detectors. It was a prototype and required the presence of a complicated computer setup, 2 video recorders, and 2 monitors, filling half a room. The set-up of the instrument in our study switches laser light sources during the acquisition of a single video line to capture quasi-simultaneous images (time separation, 0.1 milliseconds). The light exposure is limited as sources are never simultaneously active during the scan. In addition, the present instrument allows acquisition of red-free and infrared fundus photographs, as well as storing all images digitally so that any image can be recalled or transported at any time or location without any loss of image quality. The use of a PC computer platform allows the use of any software system and great flexibility in image storage and processing. It is important to realize that information density not only includes horizontal resolution but also a time component. By shifting planes of focus and angle of imaging, one can often see better details of the structure of interest and can also choose the individual frame that best shows the pathological feature of interest or the one that must be projected to guide laser therapy. Other advantages of video imaging include the ability to see moving particles in the fluorescein images; this may enhance the visualization of subretinal neovascular membranes.22
There has been some controversy regarding the issue of transit times of the 2 fluorescent dyes.21,22 We found both dyes arrived simultaneously in the early phase of our study. There is no reason for the dyes to arrive at different time points.23,24 When the relative gains of our detectors were equal, there was no evidence that one of the dyes transited faster than the other.
We found that it was easy to study the differences in fluorescence patterns and lesion localization using ICG and fluorescein with the simultaneously acquired images. We preferred the linked cursor software mode to critically and simultaneously compare locations of the ICG and fluorescein images. Color-coding of the 2 images with display of both images simultaneously could also be performed. We recognize that treatment based on ICG fluorescence has not been studied in randomized clinical trials. Clearly this is necessary, but the ability to obtain both studies simultaneously should be advantageous in designing such a trial. Using simultaneous angiography is the only way to determine the relative value of each type of angiography. Only through a large study of patients with a variety of retinal diseases using simultaneous ICG and fluorescein angiography will it be possible to critically determine the differences in vascular imaging and leakage patterns and their clinical significance.25 We do not advocate the use of simultaneous angiography for all patients. However, in those patients in whom conventional fluorescein angiography does not allow a conclusive analysis, simultaneous angiography seems to offer additional insight.
Accepted for publication November 26, 1997.
Supported by a grant from the Stern Foundation, La Jolla, Calif (Dr Freeman), the Whitaker Foundation, Rosslyn, Va (Dr Bartsch), and Deutsche Forschungsgemeinschaft, Bonn, Germany (Dr Mueller).
Reprints: William R. Freeman, MD, UCSD Shiley Eye Center, 9415 Campus Point Dr, La Jolla, CA 92093-0946.
References
Video 1 The angiography shows general hypoperfusion of the mastectomy skin flaps due to the use of Klein’s fluid for hydrodissection resulting in vasoconstriction.
Video 2 Indocyanine green angiography (ICG-A) showing hypoperfused areas (<33%) of the mastectomy flap after insertion of sizer before prepectoral breast reconstruction with implant and acellular dermal matrix (ADM).
Video 3 Indocyanine green angiography (ICG-A) showing sufficient perfusion after pre-pectoral breast reconstruction with implant and acellular dermal matrix (ADM).
Video 4 Indocyanine green angiography (ICG-A) after raising the lateral intercostal artery perforator (LICAP). Angiography visualizes perforators entering the flap.
Video 5 Intraoperative angiography confirms perforators entering the flap.
Video 6 Per-operative indocyanine green angiography (ICG-A) on donor-site/abdominal region visualizing insufficient perfusion of the right side of the deep inferior epigastric artery perforator (DIEP)-flap.
Video 7 Indocyanine green angiography (ICG-A) showing insufficient intra-flap perfusion of a deep inferior epigastric artery perforator (DIEP)-flap after transposition to the breast region and microvascular anastomoses. Patient experienced partial flap loss of the medial 20% of the flap corresponding to the intraoperative angiography.
An increasing number of women seek a breast reconstruction, due to increased survival rate after breast cancer (1). A breast reconstruction aims to increase the quality of life and obtain a new breast with an acceptable size, shape and symmetry (2-5). Sufficient perfusion is important in achieving a successful implant-based, oncoplastic- or autologous breast reconstruction. Indocyanine green angiography (ICG-A) is an intraoperative imaging modality visualizing blood flow to the tissue of interest (6-8). The real-time assessment of perfusion supports the surgeon in intraoperative decision making, which consequently leads to a decreased risk of postoperative complications and loss of reconstruction (9-16). We present the following article in accordance with the Narrative Review reporting checklist (available at https://abs.amegroups.com/article/view/10.21037/abs-21-25/rc).
ICG-A has been used to assess skin perfusion for the last two decades (17-19) and is a widely used and well described imaging technique for evaluating tissue perfusion (6,8,20). The modality is not only used to asses arterial perfusion, but has also been described for evaluation of microvascular anastomoses (21,22), venous congestion (23,24), augmentation mastopexy (25), breast reduction surgery (26) and investigation of perfusion zones (27-31).
Scoring and cut-off values in terms of sensitivity, specificity, positive predictive- and negative predictive values have been investigated by several authors (10,11,32-37). In mastectomy flaps, ICG-A has been reported with a sensitivity of 90% and specificity of 100% in reducing skin flap necrosis and overall complication rate (10,38-40). Moyer et al. suggested a cut-off perfusion score of 33% in preventing mastectomy flap necrosis (33). In autologous breast reconstruction establishment of a specific cut-off value and perfusion assessment have yet to be determined (15,41-45).
The majority of published studies on ICG-A in breast reconstruction are of lower level of evidence and consists of comparative, case and cohort studies. Only one randomized controlled trial (RCT)-study investigating ICG-A is published (15). The study investigated the use of ICG-A in deep inferior epigastric artery perforator (DIEP)-flaps and found a significant decreased incidence of fat necrosis (15).
A systematic review from 2020 on the use of ICG-A in autologous breast reconstruction, concluded that per-operative perfusion assessment by ICG-A was an effective tool in reducing fat necrosis compared with flaps assessed clinically (46). Mastectomy skin flap necrosis and the risk of repeated surgeries were reported significantly decreased in 2 reviews and 1 meta-analysis (36,37,47). A Cochrane review on ICG-A on mastectomy skin flap perfusion in immediate breast reconstructions was inconclusive due to lack of high-quality evidence (48). Johnson et al. investigated the overall use of ICG-A in breast reconstructions, and reported a reduced postoperative tissue loss when applying ICG-A, but emphasized the need for standardization (35).
In the following we present a narrative review and a description on how ICG-A may be used in implant-based, oncoplastic- and autologous breast reconstruction demonstrated by clinical examples.
ICG-A offers an objective, repeatable and real-time imaging of the vascularity and perfusion of tissue (7,49). Indocyanine green (ICG) is a water-soluble molecule excreted via the liver to the bile. The technique is repeatable due to a short half-life of 3–5 minutes. Upon intravenous injection of ICG during surgery a fluorescent near-infrared camera detects the molecule and visualizes perfusion within approximately 20 seconds (6). There is up until now no consensus on the intraoperative dose of ICG which is reported from 2 up to 250 mg (13,50,51).
Several imaging-systems exists among others the Fluobeam Clinical System® (Fluoptics, Grenoble, France, www.fluoptics.com), HyperEye Medical Systems® (Mizuho, Tokyo, Japan, www.mizuhomedical.co.jp) and IC-View® Pulsion Medical Systems. One of the most commonly used systems is the Spy-Elite Fluorescence Imaging Systemâ which is able to quantify perfusion and apply relative values of blood flow in the tissue (33,52). Wearable technology in the form of smart glasses have also been described (53).
Patients undergoing breast reconstruction should be informed of the rationale and use of per-operative ICG-A. Potential side-effects such as nausea, dizziness, discomfort, rash and sweating occur in up to 0.2–0.34%, and is thoroughly discussed with the patient (32,54-56). Patients allergic to iodine should be excluded due to risk of anaphylaxis (51).
The incidence of anaphylactic shock is rare, and occurs in approximately 1 in 42,000 patients (56). Also, though extravasation is rare, extravasation of ICG may cause reversible discoloration of the skin (Figure 1).
Figure 1 Patient with discoloration of the leg after extravasation of indocyanine green used per-operatively. The color diminished gradually within 3 months leaving no sequelae.
Mastectomy, being it nipple-sparing or skin-sparing, is performed in the plane of the subcutaneous fascia to preserve the dermal blood supply. Hemostasis is secured using bipolar diathermia. After removal of the breast tissue, the surgeon evaluates the skin flaps estimating areas in risk of potential hypoperfusion. The breast surgeon should refrain from using vasoconstrictive agents such as Klein’s fluid (Ringer lactate, lidocaine and adrenaline) to avoid distortion of the assessment of the ICG-A (Figure 2).
Figure 2 ICG-A performed on mastectomy flaps after a skin-sparing subcutaneous mastectomy using vasoconstrictive agents. (A) The angiography shows general hypoperfusion of the mastectomy skin flaps due to the use of Klein’s fluid for hydrodissection resulting in vasoconstriction (®, perfusion is <5%. (C) ICG-A color mode showed hypoperfusion indicated by the dark blue color. (D) Per-operative clinical photo of the mastectomy flaps. The patients right side mastectomy flaps are thin and discolored due to the use of vasoconstrictive agents for the hydrodissection during mastectomy. ICG-A, indocyanine green angiography.ICG-A performed on mastectomy flaps after a skin-sparing subcutaneous mastectomy using vasoconstrictive agents. (A) The angiography shows general hypoperfusion of the mastectomy skin flaps due to the use of Klein’s fluid for hydrodissection resulting in vasoconstriction ( Video 1 ). (B) Scoring perfusion by the Spy-Elite Fluorescence Imaging System, perfusion is <5%. (C) ICG-A color mode showed hypoperfusion indicated by the dark blue color. (D) Per-operative clinical photo of the mastectomy flaps. The patients right side mastectomy flaps are thin and discolored due to the use of vasoconstrictive agents for the hydrodissection during mastectomy. ICG-A, indocyanine green angiography.
A sizer of appropriate size is inserted, and dermis is sutured temporarily. Twenty-five milligrams of ICG are diluted in 10 mL sterile water, an intravenous bolus administration of ICG (Verdyeâ 5 mg/mL) of 2.5 mg/mL is followed by a 10 mL flush with normal saline (2.5 mL of ICG solution for each administration).
The ICG is injected and the perfusion scored by the SPY-Eliteâ system. A perfusion below 33% may lead to reevaluation of the reconstructive procedure by reducing volume of the sizer to eliminate the skin tension (33).
In cases with perfusion below 33% on the first ICG-A, the technique is repeated and re-evaluated using the same dose of ICG, after 20 minutes (6). Consequently, a perfusion <33% on the 2. angiography will result in excision of the hypoperfused area (if located near incision area), a smaller implant or result in reconstruction with subpectoral placement of a tissue expander (TE) (Figure 3).
Figure 3 A case where the surgeon chose not to excise the hypoperfused areas indicated by the ICG-A. (A) ICG-A showing hypoperfused areas (<33%) of the mastectomy flap after insertion of sizer before prepectoral breast reconstruction with implant and ADM (® 5 days postoperatively, perfusion is centrally <33% corresponding to the clinic. NAC, nipple areola complex; ADM, acellular dermal matrix; ICG-A, indocyanine green angiography.A case where the surgeon chose not to excise the hypoperfused areas indicated by the ICG-A. (A) ICG-A showing hypoperfused areas (<33%) of the mastectomy flap after insertion of sizer before prepectoral breast reconstruction with implant and ADM ( Video 2 ). (B) Clinical photo. The patient developed epidermolysis and necrosis 5 days postoperatively corresponding to the ICG-A. The necrotic areas were excised, the implant extracted and the patient underwent 2-stage reconstruction with TE. (C) ICG-A color mode shows central hypoperfusion as seen on the ICG-A. (D) Scoring perfusion by the Spy-Elite Fluorescence Imaging System5 days postoperatively, perfusion is centrally <33% corresponding to the clinic. NAC, nipple areola complex; ADM, acellular dermal matrix; ICG-A, indocyanine green angiography.
In cases with sufficient perfusion, the reconstruction proceeds with either a pre-pectoral implant wrapped in acellular dermal matrix (ADM) or a subpectoral implant or TE.
After completing the breast reconstruction, ICG-A is then performed again to confirm and ensure sufficient perfusion (Figure 4).
Figure 4 Pre-pectoral breast reconstruction with implant and ADM. (A) ICG-A showing sufficient perfusion after pre-pectoral breast reconstruction with implant and ADM (®, perfusion is generally >33% and indicates sufficient perfusion to proceed with the planned reconstruction. (C) ICG-A color mode indicating sufficient perfusion. ADM, acellular dermal matrix; ICG-A, indocyanine green angiography.Pre-pectoral breast reconstruction with implant and ADM. (A) ICG-A showing sufficient perfusion after pre-pectoral breast reconstruction with implant and ADM ( Video 3 ). (B) Scoring perfusion by the Spy-Elite Fluorescence Imaging System, perfusion is generally >33% and indicates sufficient perfusion to proceed with the planned reconstruction. (C) ICG-A color mode indicating sufficient perfusion. ADM, acellular dermal matrix; ICG-A, indocyanine green angiography.
Oncoplastic techniques have been used for several decades and can be applied to achieve an acceptable aesthetic result after breast conserving therapy (57-59). Corrective techniques span from Z-plasties and local flaps to larger transposition, advancement and perforator flaps (57). The oncoplastic surgery aims to balance and restore the shape of the breast subsequent to oncologic resection (59). Reshaping and relocation of tissue can compromise perfusion and makes ICG-A a valuable tool in oncoplastic breast surgery (58).
After removing the cancer and intraoperative confirmation of adequate resection, the lateral intercostal artery perforator (LICAP) flap is raised to replace volume and reshape the breast (60). ICG-A can be used per-operatively to assess and score perfusion before after raising the flap, after advancement and before wound closure (Figure 5). In oncoplastic displacement (e.g., breast reduction oncoplasty), the ICG-A technique is used as described for the displacement techniques.
Figure 5 Assessment and scoring of perfusion of LICAP-flap before the flap was deepithelialized and advanced in to the breast. (A) ICG-A after raising the LICAP. Angiography visualizes perforators entering the flap (Assessment and scoring of perfusion of LICAP-flap before the flap was deepithelialized and advanced in to the breast. (A) ICG-A after raising the LICAP. Angiography visualizes perforators entering the flap ( Video 4 ). (B) Quantification and scoring of perfusion shows sufficient perfusion of the entire flap. (C) ICG-A color mode with sufficient perfusion. (D) Clinical photo of the LICAP-flap before the flap was deepithelialized and advanced in to the breast. ICG-A, indocyanine green angiography; LICAP, lateral intercostal artery perforator.
Preoperatively a doppler ultrasonography can be used to mark the perforators or artery(ies) if the chosen pedicled flap is a muscle sparing latissimus dorsi (msLD) or a thoracodorsal artery perforator flap (TAP). Perfusion of the flap can then be scored by ICG-A [as described (33)] performed after incision around the flap to the fascia. The angiography indicates the number of perforators within the flap (Figure 6).
Figure 6 Per-operative ICG-A of a LD-flap after incision around the flap, before flap is elevated on the pedicle. The angiography visualizes the perforators entering the flap. Scoring of perfusion by the Spy-Elite Fluorescence Imaging System®. (A) Intraoperative angiography confirms perforators entering the flap (Per-operative ICG-A of a LD-flap after incision around the flap, before flap is elevated on the pedicle. The angiography visualizes the perforators entering the flap. Scoring of perfusion by the Spy-Elite Fluorescence Imaging System. (A) Intraoperative angiography confirms perforators entering the flap ( Video 5 ). (B) Quantification and scoring of perfusion shows sufficient perfusion of the entire flap. (C) ICG-A color mode visualizes perforators and perfusion. ICG-A, indocyanine green angiography; LD, latissimus dorsi.
We recommend repeating ICG-A after the flap is completely raised on its pedicle—before transposition/advancement—which allows assessment of the chosen perforator or artery in order to evaluate possible changes in perfusion—assessing the angiosome if the flap is designed as a perforator flap. The final angiography is performed after the flap is transposed to the recipient site. Areas with hypoperfusion (<33%) should be excised.
The angiographies can aid the surgeon in the intraoperative surgical decision making, and the perfusion measurement may identify areas in risk of postoperative necrosis due to hypoperfusion (Figure 7).
Figure 7 Delayed breast reconstruction using a msLD flap combined with a tissue expander. (A) Intraoperative ICG-A showed hypoperfusion (<33%) of the medial part of the flap, but the area was not excised. (B) Demarcation, epidermolysis and necrosis developed 2 days postoperatively at the medial part of the flap, corresponding to the per-operative ICG-A. (C) Take-back surgery with removal of TE and excision of necrotic tissue. (D) ICG-A confirmed sufficient perfusion and the patient healed uneventfully. Green numbers indicate the relative perfusion score. msLD, muscle sparing latissimus dorsi flap; ICG-A, indocyanine green angiography; TE, tissue expander.
For breast reconstruction using a free abdominal flap, e.g., deep inferior epigastric artery perforator flap (DIEP), superficial inferior epigastric artery (SIEA) or muscle sparring transverse rectus abdominis (msTRAM) flap, ICG-A can be used to evaluate perfusion of the flap, aiding flap design, identification of perforators and assessing perfusion zones, microvascular anastomoses, venous insufficiency etc.
A preoperative computed tomography angiography (CT-A) is done to identify the perforators and the intramuscular course of the vessels in the flap. By performing ICG-A (as described above) upon incision around the flap to the fascial level—before entering the subfascial plane—the complete number of perforators entering the flap can be identified and compared with the preoperative CT-A.
Based on this assessment, the best/most reliable perforators may be dissected, and the angiography repeated, allowing real-time assessment of the perfusion while aiding the intraoperative flap design. If the angiography indicates areas of insufficient perfusion, the surgeon is able to reevaluate and adjust the reconstructive procedure (Figure 8).
Figure 8 Planned breast reconstruction with bilateral DIEP-flap. ICG-A performed per-operatively at donor-site/abdominal region, after dissection of perforators before entering the abdominal subfascial plane, showed insufficient perfusion of the right half of the flap. The angiography aided the surgeon to reevaluate the reconstructive procedure. (A) Per-operative ICG-A on donor-site/abdominal region visualizing insufficient perfusion of the right side of the DIEP-flap (Planned breast reconstruction with bilateral DIEP-flap. ICG-A performed per-operatively at donor-site/abdominal region, after dissection of perforators before entering the abdominal subfascial plane, showed insufficient perfusion of the right half of the flap. The angiography aided the surgeon to reevaluate the reconstructive procedure. (A) Per-operative ICG-A on donor-site/abdominal region visualizing insufficient perfusion of the right side of the DIEP-flap ( Video 6 ). (B) Per-operative ICG-A. Scoring of the perfusion shows perfusion <33% on the right side of the flap. (C) ICG-A color mode depicts insufficient perfusion of the right side of the DIEP-flap. (D) Per-operative clinical photo. Area with insufficient perfusion is marked on the skin. ICG-A, indocyanine green angiography; DIEP, deep inferior epigastric artery perforator flap.
After the flap is raised with complete pedicle dissection, ICG-A is repeated allowing a final assessment of flap perfusion before transposition to the breast.
Upon completing the microvascular anastomoses, a repeated angiography may display possible hypoperfused areas of the flap, venous insufficiency or insufficient intra-flap perfusion (Figure 9).
Figure 9 Delayed breast reconstruction with a DIEP-flap (left breast). Pictures of the postoperative complications corresponding to intraoperative ICG-A. (A) ICG-A showing insufficient intra-flap perfusion of a DIEP-flap after transposition to the breast region and microvascular anastomoses. Patient experienced partial flap loss of the medial 20% of the flap corresponding to the intraoperative angiography (Delayed breast reconstruction with a DIEP-flap (left breast). Pictures of the postoperative complications corresponding to intraoperative ICG-A. (A) ICG-A showing insufficient intra-flap perfusion of a DIEP-flap after transposition to the breast region and microvascular anastomoses. Patient experienced partial flap loss of the medial 20% of the flap corresponding to the intraoperative angiography ( Video 7 ). (B) Two days postoperatively, clinical demarcation and epidermolysis of medial segment of the flap. (C) Eighteen days postoperatively, the necrosis of medial segment. (D) After secondary revision and excision of medial segment with necrosis, the patient healed with no further complications. ICG-A, indocyanine green angiography; DIEP, deep inferior epigastric artery perforator flap.
Using ICG-A intraoperatively informs the surgeon of possible insufficiently perfused areas of the flap and aids in reevaluating the breast reconstruction strategy to prevent postoperative complications.
A successful breast reconstruction requires sufficient blood perfusion preventing postoperative complications and loss of reconstruction.
ICG-A provides the surgeon with real-time accurate assessment of the tissue and intraoperative perfusion (7,49). Making information on real-time tissue perfusion available intraoperatively can assist the surgical decision making, providing the opportunity to reevaluate and adapt the reconstruction technique. Repeated intraoperative use of this imaging technique supplies valuable information on perfusion in every step of the reconstruction.
Surgical decision making often relies on clinical experience and judgement. ICG-A can assist the surgeon by providing real-time assessment, scoring and quantification of tissue perfusion.
The role of ICG-A in breast reconstructive procedures is not exhausted.
Determining cut-off values for perfusion, correlating these to postoperative fat necrosis rates or ultimately flap loss remains yet to be investigated. Moreover, further studies, exploring the role of ICG-A in postoperative monitoring, assessment of venous congestion and microvascular anastomoses may further expand the applications of ICG-A in breast reconstructive surgery.
We acknowledge Dr. Rami Mossad Ibrahim, MD. Department of Plastic Surgery and Burns Treatment, University Hospital Copenhagen for assisting the photo and video editing.
Funding: None.
Provenance and Peer Review: This article was commissioned by the editorial office, Annals of Breast Surgery for the series “Breast Reconstruction - The True Multidisciplinary Approach”. The article has undergone external peer review.
Reporting Checklist: The authors have completed the Narrative Review reporting checklist. Available at https://abs.amegroups.com/article/view/10.21037/abs-21-25/rc
Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://abs.amegroups.com/article/view/10.21037/abs-21-25/coif). The series “Breast Reconstruction - The True Multidisciplinary Approach” was commissioned by the editorial office without any funding or sponsorship. TED served as the unpaid Guest Editor of the series. The authors have no other conflicts of interest to declare.
Disclaimer: Videos and clinical photos published with this article are original. Copyright: Dr. Elisabeth Lauritzen, MD, PhD-student, Department of Plastic Surgery and Burns Treatment, University Hospital Copenhagen.
Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.
Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.
doi: 10.21037/abs-21-25
Cite this article as: Lauritzen E, Bredgaard R, Bonde C, Jensen LT, Damsgaard TE. Indocyanine green angiography in breast reconstruction: a narrative review. Ann Breast Surg 2022;6:6.