University of Groningen

The significance of preoperative vascular mapping of donor- and acceptor vessels in free flapsurgeryKlein, Steven

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Chapter 9

Summary and general discussion

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115

Summary and general discussion

Summary

Trauma, oncological resections and pressure sores can lead to major soft tissue defects, which can

create a challenge for surgical closure. Reconstructive surgery has seen great development since the

early 1960s, when the concept of axial vessels became mainstay. In the past 20 years, enormous

progress has been made in flap design and more and more flaps are based on perforating vessels that

branch off and are traced back to well-known vessels, thereby limiting donor-site morbidity. The exact

location of perforators, however, varies significantly, and preoperative vascular mapping has been

introduced to help identify the dominant perforator and its course and, as such, speed up flap harvest.

The aim of this thesis was to investigate the need for and compare various techniques for preoperative

vascular assessment in free flap reconstruction.

In chapter two the evolution of the reconstructive flap surgery is described. This evolution followed the

increased understanding of the vascular anatomy of the skin and subcutis. While the first local flaps for

reconstruction were based on a random vascular pattern, the next generation of flaps was based on an

axial vascular supply. In the Western world, surgeons such as Esser and Machot were the pioneers in

this field around the turn for the nineteenth century. (1,2) Due to the influence of surgeons, like Gillies,

the principle of axial pattern flaps was not expanded until their reinvention in 1969 by Stuart Milton. The

first axial pattern flaps were based on well-known vessels from the anatomy book, such as the radial

artery for the radial forearm flap and the thoracodorsal vessels for the latissimus dorsi flap. The harvest

of these flaps, although in that time revolutionary, is nowadays looked upon as relatively straightforward,

due to their predictable anatomy. In the recent years, more and more flaps have been described that

are based on a single perforating vessel. By the use of such perforator flaps, proper blood supply to the

flap can be combined with less morbidity at the donor site.(3)

In chapter three the “condito sine qua non” of a good vascular supply to a free flap and the donor site is

illustrated with the example of the complicated case histories of three patients in whom a free fibular flap

was harvested. The free fibula flap is the microsurgeon’s workhorse for the reconstruction of osseous or

osteocutaneous defects. Donor-site morbidity of this flap is reported to occur infrequently, and is

generally considered minor and transient. Anatomical variations of vascular patterns, prior vascular

trauma or atherosclerosis can however jeopardize the survival of the free flap and the preservation of

the tissues surrounding the donor site. The drama of flap failure and the occurrence of severe

complications at the donor site stress the importance of decent vascular assessment as part of the

preoperative work-up.

In order to validate a technique and the results of several studies, the method of measurement ought to

be standardized. However this is not always the case, as is presented in the general review in chapter

four about the example of the measurement and calculation of the ankle-arm index (AAI). Since its

introduction in 1950, a variety of methods of measurement and calculation have been used. This has

resulted in variations of its normal range and difficulty in comparing study results. Hence, the objective

of the study depicted in this chapter was to analyze the various methods used to assess AAI and its

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normal range and to construct a standardized method to assess AAI based on that analysis. This study

resulted in an inventory of the disparate AAI methods and its normal range reported in 100 randomly

selected publications and a recommendation for standardization. We concluded, that the left arm

pressure ought to be used as denominator and the mean of pressures of both tibial arteries of each leg

ought to be used for the numerator of the AAI for that leg. We advocate 0.90 as the cut-off value to

distinguish patients who need further arterial assessment.

The fifth chapter gives an overview of the various methods for vascular mapping of flaps together with

their advantages and disadvantages. The pro’s and con’s of the hand-held Doppler, colour duplex,

digital subtraction angiography (DSA), computed tomographic angiography (CTA) and magnetic

resonance angiography (MRA) are reviewed and discussed. As CTA and MRA are able to produce

detailed 3D images of the vasculature and its surrounding structures, these methods currently are

thought to be the best methods available for mapping the vasculature of donor sites of perforator flaps

with variable anatomy such the upper thigh, the donor site of the Anterolateral Thigh flap (ALT), and the

lower abdomen, donor site of the Deep Inferior Epigastric Perforator (DIEP). In flaps with standard

anatomy and superficial vasculature hand held Doppler remains the method of choice.

In chapter six the ankle-arm index (AAI) is compared to the current golden standard, the Digital

Subtraction Angiography (DSA) for the assessment of the donor site of the fibula free flap. As peripheral

arterial occlusive disease or congenital anomalies of the major crural arteries may limit the use of the

fibula free flap, these conditions should be detected preoperatively. Since DSA has drawbacks, a safer,

cheaper, more accurate and noninvasive alternative is desirable. We tested the hypothesis that AAI of

each of the three crural arteries, combined with pencil Doppler examination of the peroneal skin

perforators, would provide adequate information to restrict the use of angiography to cases in which the

outcomes of either or both of these options are insufficient. The ankle-arm index data of each of the

three crural arteries, as well as pencil Doppler examination of the peroneal skin perforators of both legs

of nine prospectively included patients and the nonoperated legs of 13 retrospectively included patients,

were compared statistically in four different ways with the preoperative angiographic findings. The

conclusion that could be drawn was that combined ankle-arm index and pencil Doppler examination is

not accurate enough to detect legs or arteries with subclinical peripheral arterial occlusive disease or

vascular variation and, hence, is not a sufficient basis on which to develop the surgical plan for a fibula

free flap.

In Chapter seven 3D-TOF Magnetic Resonance Angiography (MRA) is compared to the current golden

standard, the Digital Subtraction Angiography (DSA) for the vascular assessment of the fibula free flap

donor site. Fifteen consecutive patients, scheduled for free vascularized fibular flap transfer, were

subjected to DSA as well as MRA of the crural arteries of both legs (n=30). Two radiologists randomly,

blindly and independently assessed all DSA and MRA images. Each of the assessors scored the

degree of stenosis or hypoplasia of various segments on a 5-point scale from 0 (occlusive) to 4 (no

stenosis). In addition, the number of cutaneous perforators was scored and the assessors were asked if

they would advise against fibula harvest and transplantation based on the images. Substantial

agreement of stenosis severity scores was found between the two imaging techniques. The sensitivity

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of MRA to detect a stenosis compared to DSA was 0.79, and a specificity of 0.98. In 53 out of 60

assessments, advice on suitability for transfer was equal between DSA and MRA. And the median

number of cutaneous perforators per leg was one for DSA as well as for MRA (p = 0.142). The results of

this study suggest that MRA is a good alternative to DSA in the preoperative planning of free fibula flap

transplantation.

A successful transplantation of tissue is not only dependent on the good vascular supply of the flap, but

also on the condition of the vessels at the recipient site. As presented in chapter eight anatomic

variations, atherosclerosis and irradiation damage to the acceptor vessels can result in a challenging

and troublesome microsurgical procedure. The possibility to preoperatively assess the presence of

atherosclerosis or irradiation damage to the vessels is studied at the example of the internal mammary

artery that is used as recipient vessel during free flap breast reconstructions. Pre-operative angiography

findings were compared to the degree of vascular damage found during the operation, the clinical

course of the reconstruction and the histology of segments of the recipient artery. A total of 34 patients

were included with the intention of free flap breast reconstruction after radiation therapy. In total 40 free

flaps were transplanted for breast reconstruction. Twenty-one internal mammary arteries had been

within the field of irradiation and 19 out of field. In only two out of six patients with aberrant

angiographies the internal mammary artery had been within the field of radiation. Based on this study

the conclusion had to be drawn, that the damage to the internal mammary vessels cannot always be

detected pre-operatively by angiography, nor by intraoperative examination.

General Discussion

As stated before, in flaps with a variable vascular anatomy or with a suboptimal vascular state, for

example due to atherosclerosis, it is important to be informed about course and quality of the vessels

before the flap elevation starts. Not only the flap pedicle needs to be in good shape to prevent serious

complications after transfer, but also the vessels at the recipient site need to be of good quality, while

the remaining vessels at the donor site need to be able to supply the donor site after the harvest of the

flap. This thesis aimed to shed light on preoperative vascular mapping in different type of

reconstructions and to investigate which method is the most valuable for which type of reconstructions.

All vascular mapping methods have their own advantages and disadvantages.(4-6)

The ankle-arm index (AAI), is a blood pressure index, in which the left arm pressure ought to be used as

denominator and the mean of pressures of both tibial arteries of each leg ought to be used for the

numerator of the AAI for that leg. The advantages are its non-invasiveness, small size, low costs,

portability and the ease to perform the examination. But the disadvantages are its insensitivity to detect

moderate or mild stenosis and it’s lack on information on the vascular state of a single crural vessel.

The advantages of the hand-held Doppler (HDD) are comparable to the AAI: its non-invasiveness, small

size, low costs, portability and the ease to perform the examination. In addition, there are special

sterilized probes available for intra-operative use. The main disadvantage of the most widely used

Doppler probe (8 MHz) is, that it only detects vessels to a depth of 20 mm. Besides, one can never

know for sure what vessel is producing the Doppler signal picked up by the HHD. Furthermore, this

technique does not create a three-dimensional (3D) image of the vasculature and its surrounding

anatomy than can be stored and retrieved later.

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Similar to HHD, Color Duplex Sonography (CDS) is non-invasive. An advantage compared with the

HHD is its ability to offer more information about anatomy of the vessel and its perforators in reference

to its surrounding tissues, and it can quantitatively analyze which perforator is the dominant one. The

disadvantage of CDS however, is the fact that only skilled personnel, who also have knowledge of free-

flap anatomy, can perform the investigation. In addition, it is less reproducible because of its real-life

dynamics. Another disadvantage in comparison to CTA, MRA and DSA is that CDS - just as HHD -

does not reproduce a 2D or 3D image of the complete vascular anatomy, which can be used by the

surgeon during flap design or flap elevation

The reported advantages of Digital Subtraction Angiography (DSA) include the facts that it gives a 2D

image of the intraluminal vascular anatomy and information about atherosclerotic changes. A

disadvantage of DSA is that it is a time-consuming, invasive technique necessitating the use of iodinate-

contrast medium, which may cause vascular or renal damage as well as allergic reactions. In addition,

there is a radiation dose to be considered. The vasoconstricting effect of the contrast medium, make

exact measurement of the vascular diameter and the assessment of small-caliber vessels unreliable.

Furthermore, the patient has to stay in supine position after the angiography for several hours, to allow

the puncture site to seal. This makes hospital admission often mandatory and therefor makes this

imaging modality relatively expensive. Finally, there is a risk for the development of false aneurysms at

the puncture site.

The advantage Computed Tomographic Angiography (CTA) offers is that it provides an image with

accurate visual details on the intraluminal calibre and course of the vessels and their relationships with

other anatomic structures in a 3D image. This allows surgeons to develop a dissection strategy and opt

for a certain perforator prior to surgery, making the actual dissection safer and swifter. The

disadvantages of CTA are its radiation dose, which is reported to be 5.6 mSv, and the necessity to use

iodinated contrast medium with its previously listed disadvantages. Especially, the vasospastic action is

a serious drawback, because it can make the accurate assessment of small-calibre vessels difficult.

The big advantage of Magnetic Resonance Angiography (MRA) are that it works with magnetism

instead of radiation and. Depending on the software used, it can be used without a non-iodine contrast

medium, making it a relatively safe procedure for the patient. MRA produces a 3D image, which allows

surgeons to accurately assess the course and diameter of the vessels and their relation to other

surrounding structures. The reported disadvantages of MRA are its relatively high costs. Besides, it

cannot be used in claustrophobic patients or a patient with implants containing ferrous metals because

of the scatter artefacts influencing the image quality.

Apart from the descriptive studies in this thesis (chapter two, three, four and five) we investigated the

AAI, HHD, DSA and MRA in comparative studies (chapter six, seven and eight). We concluded that a

combined ankle-arm index and pencil Doppler examination is not accurate enough to detect arteries

with subclinical peripheral arterial occlusive disease or vascular variation and, hence, gives insufficient

information to develop the surgical plan for a free flap of the lower leg. Furthermore, using the example

of the free fibula flap, we drew the conclusion that MRA is a good alternative to DSA in the preoperative

planning of free flap transplantation of the lower leg. Also this thesis showed (in case of the internal

mammary vessels) that DSA is not sensitive and specific enough to detect the irradiation-induced

damage of vessels.

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In the most recent literature there is a clear tendency towards MRA being used more over and replacing

techniques such as DSA and CTA. (7-9) In the planning of free fibula flaps, MRA is able (in

concordance to our own results) to detect hypoplastic vessels, stenoses, occlusions, or atherosclerotic

changes of the vessels, and enables both accurate assessment of the quality of the main vessels and

their septo- or musculoccutaneous perforators.(7,10-15) CTA is suggested to be a good imaging

modality for the lower leg arteries as well.(16-18) In perforator flaps the use of both MRA (8,9) and CTA

(19-24) is being described. The advantage of CTA is that it is able to detect vessels with a smaller

diameter (<0.5mm).(25) Compared to CTA the advantages of MRA are, as stated earlier, that it is

performed without radiation and there is no need for iodinate contrast medium, which makes it less

harmful for patients.(8-26) It should however be noted that prospective controlled comparative studies

about the use of MRA and CTA in the planning of free fibula flaps are lacking.

Combining the outcome of our studies and the literature we conclude that MRA and CTA are currently

the best methods available to map the vasculature of crural vessels and perforator flaps in general. (4)

In the planning of thin pedicled flaps that are planned close to a defect, in flaps with a more

straightforward anatomy and for intra-operative use, the HHD remains to be mapping method of

choice.(4) DSA is slowly fading out and CDS can be used as an alternative, whenever there are contra-

indications to the use of the other methods of investigation.

When evaluating the outcome of a study, especially a comparative study, it is of importance to look at

the methods used. The strong points of our studies are the prospective and comparative study design.

The investigated technique was compared to the gold standard at that moment. There are however also

limitations, especially with regard to the news value of some of this work in 2013. The field of vascular

mapping is developing so rapidly, that during the design, execution, analysis and report process new

developments make some of this work at present already a bit outdated. When we performed our study

the 1.5 Tesla 3D TOF-MRA technique was the currently used method to depict crural vessels. But from

that time MRA-techniques developed very rapidly.(27-30)

In clinically used scanners the magnetic field increased from 1.5 to 3.0 Teslas in strength. For research

purposes already 7.0 Tesla scanners are used. By the use of higher Tesla scanner it is possible to

improve the signal to noise ratio and the spatial and temporal resolution. As we used a 1.5 Tesla

scanner it is obvious, that with the use of a 3.0 Tesla scanner the resolution of the depicted vessels

could have been improved. At present time, the most clinics still use a 1,5 T MRI scanner and therefore

the outcome of this study however would probably be the same.

Parallel to the improvement of the scanners, new scan techniques have beeing developed, to depict

vessels more accurately, than with the TOF-MRA technique we used. With MRA it is possible to depict

vessels by two different techniques, the flow-dependent angiography (FDA) and flow-independent

angiography (FIA).

The FDA MRA-technique can be divided into Time-of-Flight (TOF) and Phase-Contrast (PC). In TOF-

MRA flowing blood gives a much higher signal than stationary tissue, but areas with slow flow or flow

that is in plane of the image may not be well visualized. With PC-MRA slow flow can be detected much

better and the velocity of moving blood can be detected as well. The disadvantage of PC-MRA is that

the flow can only acquire flow in one direction at a time. To give a complete image of flow, 3 separate

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image acquisitions in all three directions must be computed. Despite the slowness of this method, the

strength of the technique is that in addition to imaging the flowing blood, quantitative measurements of

blood flow occur at the same time.

In general, slow blood flow is a major challenge in FDA-MRA, because the differences between the

blood signal and the static tissue signal are small. To increase blood signal, which is especially

important for very small vessels or slow flow, contrast agents may be used. Therefore Contrast-

Enhanced (CE) FIA-MRA has been developed. The use of contrast agent is currently the most common

method of acquiring MRA. The contrast medium is injected into a vein, and images are acquired during

the first pass of the agent through the arteries. If the timing of the scanning is correct, the images are

usually of a very high quality. But if the timing is bad or “blood-pool agents” are used the depiction of the

arteries is disturbed by venous overprojection.

Since the injection of contrast agents may be dangerous for patients with renal failure, non-contrast-

enhanced techniques have been developed. These methods are based on the differences of T1, T2 and

chemical shift of the different tissues of the voxel.

The acquisition of the images is changing as well from 3D, which we used, to 4D.(31) Three

dimensional data acquisition is helpful when dealing with complex vessel geometries where blood is

flowing in all spatial directions. The big advantage of the new 4D technique is that the arterial and

venous phases can be divided. In order to overcome the venous overlay and to gain dynamic flow

information the most recent development was the Triple-TWIST MRA (Time-resolved angiography With

Interleaved Stochastic Trajectories), which seems to become the new standard as imaging investigation

in patients suffering from peripheral arterial occlusive disease.(31) With this technique multiple fast

series are obtained of the same area during contrast injection. The maximum intensity image of each

series is selected. All these images together form a dynamic MRI angiography series with high

resolution, without the venous over projection.

Furthermore development of new software packages made it possible to not only asses vascular

imaging via the hospital network, but also for authorized external users. (e.g. Siemens IHE Integrating

Healthcare Enterprise – XDS-1b). This increase in accessibility of the imaging data facilitates expert

consults all over the world and preoperative surgical planning from outside the hospital.

With these improvement in technique we expect that, preoperative mapping in free flap surgery and

especially the role of MRA will get an even more dominant role and will enable surgeons to analyse

more key-aspect of the surgery prior to the surgery itself in the future.(32) Therefore, we expect that the

role of a radiologist familiar with free flap surgery will become more prominent in a reconstructive team

and will create a new dynamic within the team. To combine the necessary knowledge of the different

specialists, we believe that a reconstruction should be discussed and performed in a multidisciplinary

team. Depending on the location of an existing or expected defect, the team should consist of an

oncologist, the ablative surgeon (general surgeon, ENT surgeon, maxillofacial surgeon, orthopaedic

surgeon, gynaecologist, or neurosurgeon), a radiologist, the reconstructive plastic surgeon and an

anaesthesiologist.

A good example of how pre-operative planning is evolving is the Rohner technique for mandible or

maxilla reconstruction, in which the bone segment of a fibula or iliac crest flaps are planned prior to

surgery to fit a defect.(33-37) A CTA is made during the workup that not only allows for vascular

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imaging, but also generates data that enables the 3D reconstruction of the bony component. The

reconstruction is then further optimized, by creating pre-manufactured cutting guides, reducing the

constraints of sometimes unpredictable intraoperative environments, and maximizing bony contact. With

these techniques the implants that are required for dental bridges can even be placed prior to the bone

transfer, creating a reconstruction, which can immediately bare weight post-surgery. (33) This CAD-

CAM (computer-aided design and manufacturing) technology and the use of stereolithographic models

can improve the accuracy of the surgical result and the intraoperative efficiency.(34,36-38) These

techniques seem to offer improved patient outcome and the reduction of complication and non-union

rates due to this CAD-CAM approach. But there are no comparative studies to investigate the long-term

results in a larger patient group, concerning patient outcome and the reduction of complication and non-

union rates due to this CAD-CAM approach.

Suggestions on future research

Based on our finding during this research, we have several suggestions for future research in the field of

free flap surgery.

1) We showed that the Ankle-Arm Index is insufficient in the preoperative work-up for a free fibula

flap, but we believe that MRA is a good alternative to DSA in the pre-operative work-up of free

fibula flap transfers for reasons stated before. Although the sensitivity found in our study for the

MRA should have ideally been higher, we believe that with current developments with regards

to MRA this is only a matter of time. Although DSA is still advocated as the golden standard for

the detection of peripheral arterial occlusive disease in recent literature,(28) we do believe, that

this technique is becoming more and more obsolete.

To prove that CTA and MRA are just as or even more accurate than DSA in the detection of

peripheral arterial occlusive disease, a comparative study should be conducted, using the

newest scanners and scanning protocols. To investigate the resolution power and the accuracy

of these imaging modalities in the detection of vascular stenosis precisely a comparison to an

anatomical dissection is desirable. It is obvious that this can only be performed in an animal

study.

2) With regards to the preoperative mapping of the recipient vessels, DSA did not prove to be

reliable. We however believe that there are selected cases in which preoperative mapping of

the recipient vessels is necessary, for example after previous surgery or irradiation. In these

cases CTA, MRA or colour duplex could be of additional value, depending on the size and

location of the vessels. Future research can focus on the indication for and the necessity of

preoperative imaging and which method should be used.

3) As discussed above, new developments in the pre-operative planning is virtual surgery in which

key-points of the surgery can already be performed in a virtual setting. Thereby the surgery can

become more straightforward and safer and the results can be optimized. Until now CTA has

been predominantly used for these purposes. We believe however, that if MRA can be used for

these purposes this would further add to patient safety. But due to scattering with metal

implants MRI might not be the most suitable imaging method.

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