Abstract
OBJECTIVE:
Incidence of patients requiring complex soft tissue or osseous reconstruction has dramatically increased. However most of the monitoring systems have limitations in tissue penetration and are not able to detect microvascular complications after transplantation of so-called buried-flaps, that have no contact to the surface.
Aim of the study was to assess contrast enhanced ultrasound (CEUS) as monitoring tool after buried flap transplantations.
METHODS:
20 patients were examined after buried flap transplantation using CEUS. Quantitative perfusion analysis (TIC) was performed with an integrated perfusion software using stored cine-loops. Two perfusion-parameters, time to PEAK (TtoPk) and area under the curve (Area), were evaluated using TIC analysis.
RESULTS:
Minor complications were observed in 3 patients. In these patients a delayed contrast agent wash-in and wash-out was observed. Additionally the perfusion values TtoPk (sec.) and Area (relative Units) were clearly different in the patients with minor complications: TtoPk: 32.0 sec; Area 425.5 rU (without complication), TtoPk: 38.6 sec.; Area: 18.3 rU (wound healing disturbance) and TtoPk: 14.4 sec.; Area: 105.9 rU (hematoma).
CONCLUSION:
As CEUS can assess microvascularization almost depth-independent, CEUS is an unique method to assess global flap perfusion after buried flap transplantation.
Introduction
Free flap and perforator flap surgery were evolved into a highly reliable tool as a means to reconstruct complex soft tissue defects after trauma, infection or tumor resection. Most contemporary series have reported success rates after free flap transplantation of 95 percent and higher [16, 26]. Despite these improving success rates, microvascular failure remains a costly complication. As ischemic tolerance of the flap tissue is limited to a few hours, salvage rates have been reported to be inversely related to the time interval between the onset of ischemia and its clinical recognition [16, 28]. Therefore monitoring of free flaps remains of major importance. Unfortunately clinical symptoms of a compromised perfusion mostly occur if irreversible damage of the free flap has already been installed. An unrecognized ischemia of a free flap may necessitate further complex surgery and can result in sepsis and/or death. This problem becomes particularly apparent in so called buried flaps that are located under the skin surface and cannot be assessed from exterior. By virtue of their location buried flaps cannot be visualized directly. This placement limits the majority of conventional postoperative monitoring techniques and devices [13, 28]. Most of these monitoring systems have limitations in feasibility, sensitivity or acquisition cost. However, those techniques that are able to detect buried flap perfusion, such as angiography/endoscopy and implantable Doppler probe sonography, are invasive and have associated risk [16].
In opposition contrast enhanced ultrasound (CEUS) enables the qualitative assessment of deep tissue layers with high-resolution transducers. Additionally, changes of microvascularization can be detected dynamically and semi-quantitative analysis of tissue perfusion can be performed [2, 31]. In previous studies CEUS was used to detect vascular disturbances and semi-quantitative analysis was performed [3, 15]. CEUS was suggested as a non-invasive devise to detect changes of microvascularization in buried flaps.
Goal of the study was to evaluate the efficacy of CEUS in the monitoring of buried flaps used in patients requiring complex reconstruction. We hypothesize that CEUS could serve as a useful monitoring tool for buried flaps, particularly in situations in which the bedside examination is equivocal and that CEUS could help to detect impaired microvascularization after buried flap transplantation.
Material and methods
Contrast enhanced ultrasound (CEUS)
The technical aspects of CEUS examination were published by Greis et al. in 2014 [11]. The following paragraph provides a short summary of the technical procedure. Ultrasound examination was performed by an experienced radiologist (more than 5000 ultrasound examinations per year) with high-resolution multifrequency probes (1–5 MHz, 6–9 MHz, 6–15 MHz, LOGIG E9/GE), which allow high-resolution contrast enhanced ultrasound acquisitions. The patients received a peripheral venous bolus injection of 1–2.4 ml sulfur hexafluoride microbubbles (SonoVue®, Bracco, Italy) through a cubital vein, followed by 10 ml NaCl. The mechanical index was regulated to values <0.2, which enabled the “low MI-technique” of CEUS. Digital raw data were stored as cine loops up 1 min for perfusion curve evaluation of the transplants and then up to 5 Min in sweep technology for the complete flap. In order to minimize the artifacts during the first 60 seconds, the scanning was performed without changing the position of the transducer in the contour of the transplant. Afterwards the examination of the flap and the surrounding tissue was performed in sweep-technique for detection areas of reduced enhancement like hematomas or particularly necrosis. If areas of reduced contrast enhancement were detected, these parts were selectively recorded for more than 60 seconds with a cine sequence after another bolus injection of 1–2.4 ml of ultrasound contrast agent (SonoVue® Bracco, Italy). The digitally stored cine loops were post-processed on the integrated computer workstation (LOGIQ E9/GE). Before contrast application flow evaluation of the surrounding vessels up to the anastomosis was performed with Color Coded Doppler sonography (CCDS) and Power Doppler (PD) using low flow parameters (Pulse Repetition Frequency (PRF), flow adapted, gain optimized without artifacts and wall-filter needed less than 100 Hz).
For the time of examination the extremity was embedded as well as possible and cushioned if necessary in order to avoid motion artifacts.
Quantitative analysis of capillary perfusion with time intensity curve (TIC) analysis
Depending on the required penetration depth three different ultrasound probes were used to assess microvascularization with CEUS. In order to access the best spatial resolution mulifrequency linear probes were used whenever possible. However for deeper tissue areas convex probes have to be used. Briefly summarized: for the surface (up to 3 cm) a high-resolution multifrequency linear probe (6–15 MHz) was used. Up to 8 cm another multifrequency linear probe (6–9 MHz) and for deeper tissue layers a multifrequency convex probe (1–5 MHz) with the option of Harmonic imaging (THI) and CEUS was used.
TIC-Analysis is an integrated software for the quantification of tissue perfusion first published in 2007 [14]. In post processing up to 8 regions of interest (ROI: 30 mm×10 mm) were set to a maximum penetration depth of 8–10 cm. The first ROI was set 10 mm below the flap surface. The average contrast intensity of the region of interest (ROI) is displayed as a function of time. The curves of up to 8 ROIs can be displayed simultaneously and compared to each other. Semi-quantitative perfusion parameters can be extracted from the time intensity curve, i.e. time to peak (time from the first image frame to peak intensity frame) or area under the curve. Time to PEAK (TtoPk) correlates to the velocity of microvascularization and is given in seconds (sec.) whereas area under the curve (Area) correlates to the blood volume in the evaluated tissue area and is given as relative units (rU). With this tool, perfusion characteristics of the different ROIs can be compared and analyzedquantitatively.
The Sulfur hexafluoride microbubbles (SonoVue®, Bracco, Italy) (3–10 μm) enables a unique dynamic vascular imaging technique up to the capillary perfusion. Additionally special ultrasound technologies with pulse inversion and amplitude modulation enable an angle independent image acquisition without blooming or motion artifacts. Besides the visualization of the capillary bed this is of great advantage compared to color-coded Doppler sonography.
Clinical study
Twenty consecutive patients were evaluated after undergoing buried flap transplantation, using contrast-enhanced ultrasound to assess flap viability. All surgical procedures were performed by an experienced plastic surgeon. All patients underwent the same postoperative treatment as follows: 15.000 IE/24 h heparin and 1000 ml/24h of HES (6%, average molecular weight: 130000 Da, Fresenius Kabi, Germany) for the first 5 days.
A member of the microsurgery team was present for each ultrasound examination to identify the location of the flap. The same radiologist performed the ultrasound examination. Ultrasound examination was performed during the first 72 postoperative hours with a multifrequency probes. Written informed consent and permission of the local ethical board was obtained for all patients prior examination.
The clinical study was performed at the Department of Plastic Surgery, Department of Cranio-Maxillofacial Surgery and the Department of Radiology, University Medical Centre, University of Regensburg, Germany. The study was conducted in full accordance with the Somerset (South Africa, 1996) amendment of the Declaration of Helsinki (1964).
Results
In this trial 20 patients who received reconstruction using buried flap transplantation between October 2010 and May 2012 were included (Table 1). All transplant were buried at least one centimeter below the surface and no additional monitoring island was installed (Fig. 1). The average follow-up was 4.5 months. The average age was 54±12 (standard deviation) years (range was 31–75 years), eight were male and twelve were female. Etiology of the wound defect was trauma in four cases, infection in five cases, malignant disease in ten cases and vascular disease in one case.
Complications
Three complications occurred in the 20 buried flap procedures. Two patients developed a postoperative hematoma requiring surgical intervention and drainage. In one patient a local wound-healing disturbance was observed and underwent single debridement and secondary wound closure. All complications occurred after breast reconstruction with DIEP flaps. These patients achieved a successful outcome and needed no further surgical interventions.
Hematoma
The qualitative analysis in B-scan mode showed a hypoechoic signal in the corresponding tissue area (Fig. 2). The interpretation of this effect was facilitated by contrast defects (Fig. 3) and a delayed contrast-agent wash-in and wash-out in the CEUS analysis. This qualitative impression was proved by low perfusion values in the TIC-Analysis of the surrounding tissue: TtoPk: 5.52 sec; Area: 44.24 rU (yellow ROI), TtoPk: 14.95 sec., Area: 25.10 rU and in the area of the hematoma (turquoise ROI) and TtoPk: 14.38 sec.; 105.84 rU (red ROI) (Fig. 4).
Local wound healing disturbances
A normal echogenicity was observed in B-scan mode. However a delayed contrast agent wash-in and wash-out was observed especially in the superficial tissue. This effect was confirmed by low perfusion values in the superficial areas: TtoPk: 38.57 sec. and Area: 18.25 rU (yellow ROI). However in the deeper tissue layers and in the adjacent tissue the perfusion was reduced but almost sufficient: TtoPk: 21.76 sec.; Area: 231.09 rU (turquoise ROI), TtoPk: 24.64 sec.; Area: 224.00 rU (red ROI), TtoPk: 24.64 sec.; Area: 408.30 rU (green ROI) and TtoPk: 24.41 sec.; Area: 473.92 rU (orange ROI) (Fig. 5).
No complication
The postoperative course of the remaining seventeen buried flaps was completely uneventful. In B-scan mode no abnormalities were detected. The inflow of the first contrast agent bubbles were seen after 12–20 seconds and a homogenous distribution of the contrast agent in all tissue layers could be observed (Fig. 6). The semi-quantitative perfusion analysis showed almost an equal perfusion in all different tissue layers (Fig. 7) with the following mean perfusion values: TtoPk 27.28±29.00 sec.; Area 467.09±205.35 rU (1-2 cm), TtoPk 27.66±16.14 sec.; Area 403.17±132.51 rU (2-3 cm) and TtoPk 40.82±40.00 sec.; Area 406.15±145.21 rU (3-4 cm).
Discussion
The introduction and refinement of microvascular surgery and the advances in microsurgical technique have dramatically improved the care of patients requiring complex reconstruction. However the ability to reconstruct defects using free and local flaps in buried position is especially challenging for monitoring techniques as most technologies just offer a penetration depth below 1 cm or require a disproportionately complex examination effort. However monitoring of flap perfusion in buried position is vital to enhance salvage rates in the event of impaired flap perfusion in order to prevent flap necrosis. Thus various monitoring devices tried to be installed over the last decade [10].
In contrast to other monitoring systems ultrasound enables a dynamic visualization of both, the macro- and the microcirculation with only one single device. Bigger threats like hematomas or thrombosis can be detected in real-time. Furthermore with high resolution probes and low flow parameters (Pulse Repetition Frequency (PRF), Filter) the integrity of the anastomotic vessels can be examined using Color coded Doppler sonography or Power Doppler. Besides to color coded Doppler sonography CEUS enables a fast, angle independent examination up to the capillary microvascularization. Additionally an objective semi-quantitative analysis of the microcirculation can be performed using an integrated perfusion software based on the analysis of the stored cine-loops. As tissue penetration of ultrasound is only slightly limited [4, 8] buried flaps can be estimated almost unrestrained. In previous studies principles of imaging and quantitative analysis of microcirculatory disorders with CEUS could be demonstrated [2, 31].
Aim of this study was to evaluate the efficacy of CEUS for monitoring tissue perfusion after buried flap transplantation.
Using a new generation contrast agent, sulfur hexafluoride microbubbles (SonoVue®, Bracco, Italy), a dynamic evaluation of the tissue capillary vascularization was possible. Additionally capillary perfusions analysis was performed using an integrated perfusion software. Region of interests were set up to a penetration depth of 10 centimeters and the semi-quantitative parameters time to PEAK (TtoPk) and Area under the curve (Area) have been calculated for every centimeter separately.
Three out of twenty patients after buried flaps transplantation had to be revised due to hematomas or wound healing disturbances. All three patients showed a subjective reduced contrast agent wash-in and a delayed wash-out in the corresponding area. This qualitative impression of a reduced flap perfusion was proven by very low values in the perfusion analysis. All three flaps could be salvaged after immediate revision surgery and had successful outcomes.
Compared to other monitoring devices like the handheld Doppler CEUS may be more invasive and less mobile, however the handheld Doppler cannot reliably differentiate vessels supplying a the transplanted tissue from adjacent vessels in the recipient bed [30]. The sole use of color coded duplex sonography is frequently described in literature for buried flap monitoring [6, 29]. However a report of 77 buried flaps monitored with color coded sonography could not prove increased salvage rates [5]. Although ultrasound is almost available in every department, the results do not favor the use without the support of contrast agent [29]. Continuous monitoring methods like the implantable Doppler system, near-infrared spectroscopy, and laser Doppler flowmetry have all been reported to detect vascular complications in time [1, 33]. Besides costs, the limited penetration depth and the susceptibility to motion artifacts limit the application of these devises for buried flaptransplantation.
In contrast to contrast enhanced computer tomography (ceCT), contrast enhanced magnetic resonance tomography (ceMRI) or contrast enhanced digital angiography (DSA) CEUS enables a mobile, bedside data acquisition during operation or on the intensive care units that can be repeated arbitrarily. Additionally there is no dosage limitation of SonoVue® and no limitations due to renal failure are reported.
Weakness of this application are the cost up to 85 € for 5 ml of SonoVue®, the high acquisition costs of a high-end ultrasound device (up to 100.000 €), and the need of an experienced examiner. However Westwood et al could demonstrate the cost effectiveness of CEUS compared to MRI and CT in 2013 [32]. Despite the promising results, the sample size was too small to set any thresholds of a sufficient buried flap perfusion. Further trials with a larger patient population are necessary to confirm these first results.
Conclusion
In conclusion CEUS seems to be capable of detecting changes of buried flap perfusion in order to improve postoperative survival of buried flaps. The objective perfusion values TtoPk und Area facilitate an interpretation of the flap perfusion. We hypothesize that CEUS could serve as a useful monitoring tool for buried flap transplantation, particularly in situations in which the bedside examination is equivocal.