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Journal of Cosmetic and Laser Therapy

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Prospective 3D analysis of facial soft tissueaugmentation with calcium hydroxylapatite

Filip Simunovic, Stefan Schlager, Michaela Montanari & Niklas Iblher

To cite this article: Filip Simunovic, Stefan Schlager, Michaela Montanari & Niklas Iblher (2017)Prospective 3D analysis of facial soft tissue augmentation with calcium hydroxylapatite, Journal ofCosmetic and Laser Therapy, 19:5, 283-289, DOI: 10.1080/14764172.2017.1307411

To link to this article: http://dx.doi.org/10.1080/14764172.2017.1307411

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Prospective 3D analysis of facial soft tissue augmentation with calciumhydroxylapatiteFilip Simunovica, Stefan Schlagerb, Michaela Montanaric, and Niklas Iblherd

aDepartment of Plastic and Hand Surgery, Freiburg University Medical Center, Freiburg, Germany; bDepartment of Biological Anthropology,University of Freiburg, Freiburg, Germany; cPrivate Practice for Plastic and Aesthetic Surgery, Bochum, Germany; dPrivate Practice for Plastic andAesthetic Surgery, Freiburg, Germany

ABSTRACTBackground: Facial rejuvenation is an expanding field with an increasing number of treatment mod-alities. Several non-autologous filler materials are available for soft tissue augmentation. Calciumhydroxylapatite (CaOH) is aimed at increasing collagen neosynthesis and thereby producing long-termaugmentation effects. Despite a multitude of observational reports, the field is suffering from lack ofquantitative morphometric evaluation methods. Objective: The objective of this proof-of-principle studywas to investigate whether the effects of facial tissue augmentation with CaOH (RADIESSE™) can bequantified and followed up using 3D surface scanning. Methods: 3 female subjects received augmenta-tion of the mid and lower face with CaOH. The faces were recorded prior, directly after, and two weeksand six months after the injection using standardized photos and 3D scanning. Computational analysisallowed quantifying the change in volume and displacement of the facial surface. Additionally, a patientsatisfaction questionnaire was administered. Results: In all subjects, increase in facial volume could bequantified and was present after two weeks and six months. Conclusions: 3D surface scanning is anadequate tool for objective quantification of changes after facial augmentation with filler materials.Persistent volume augmentation after CaOH injections could be quantified after two weeks and sixmonths. Evidence level: IV.

ARTICLE HISTORYReceived 23 March 2016Accepted 12 March 2017

KEYWORDSCalcium hydroxylapatite; 3Dscan; facial volume;rejuvenation

Introduction

Soft tissue fillers are an expanding palette of products offeringnonsurgical correction of age-related facial changes. Whereasbotulinum toxin injections to the upper face paved the wayfor nonsurgical facial rejuvenation in the early 2000s, a rangeof materials aimed at restoring fullness to the middle andlower face followed. While most permanent fillers are proneto complications and thus hyaluronic acid is established as themost widespread facial soft tissue filler, calcium hydroxylapa-tite (CaHA) is a further substance that has been used increas-ingly since its Food and Drug Administration approval in theUnited States in 2006. It is not immunogenic, since CaHA is anormally occurring component of bone and teeth. CaHAmicrospheres are delivered in a polysaccharide carrier. Theaugmentative effect of the injection is immediately evident.Following injection, the carrier gel is dissolved, and it issuggested that the remaining microspheres stimulate fibro-blast growth and collagen production (1,2), thus causing alonger-lasting augmentation effect. Eventually, the micro-spheres dissolve into calcium and phosphate, which are sub-ject to the physiological ion homeostasis of the body.

Several investigations addressed the effects and their per-sistence after CaHA injections for facial augmentation, show-ing a low rate of complications and generally high acceptance

and satisfaction levels. The duration of effect achieved withCaHA has been reported to last as long as 18 months (3),12–24 months (4) or only 6 months (5,6). In a further study,over 80% of the patients claimed persistence of the results at12 months after injection (7). Moers-Carpi et al. comparedCaHA to hyaluronic acid for treatment of the nasolabial foldsand found better and longer-lasting results with CaHA (8,9).Another group found that CaHA is superior to human col-lagen for rejuvenation of the nasolabial folds after an observa-tion period of 6 months (10).

The above-mentioned studies are contributions to themounting body of evidence that CaHA is a reliable, long-lasting and safe facial filler. However, these, as well as themajority of studies in the field of facial fillers, are marred bythe lack of objective and quantitative morphometrical exam-ination criteria as they mostly rely on patients’ and doctors’subjective and descriptive evaluations of the results. Whereasthere are clearly large intercultural and individual differencesbetween aesthetic standards, it is our opinion that it should bethe goal of a scientific outcome evaluation of any medicalprocedure to develop reproducible and quantifiable measure-ments to evaluate the achieved results of the intervention. Upto recently, the technological options to evaluate the complexand interacting facial soft tissues were limited to clinical

CONTACT Filip Simunovic filip.simunovic@uniklinik-freiburg.de Department of Plastic and Hand Surgery, Freiburg University Medical Center, Hugstetterstr.55, 79106 Freiburg, Germany.Color versions of one or more of the figures in the article can be found online at www.tandfonline.com/ijcl.

Supplemental data for this article can be accessed on the publisher’s website.

JOURNAL OF COSMETIC AND LASER THERAPY2017, VOL. 19, NO. 5, 283–289https://doi.org/10.1080/14764172.2017.1307411

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observation and evaluation of photographs. Gatherwrightet al. have evaluated the 3D outcome of CaOH injections ina cadaver model and showed a volume increase and liftingeffect (11), yet to this date there is no study evaluating three-dimensional outcome of this filler treatment in livingindividuals.

To this end, we have previously described the use of three-dimensional surface scanning for quantifying facial soft tissuechanges (12). This technology has also been used by otherauthors to record soft-tissue changes in the face (13–15), butit has not yet gained widespread acceptance. This study wasdesigned to quantify the effects of an intervention (CaOHinjection) using this method. Additionally, we aimed at obser-ving the intermediate-term changes after injection over a 6-month period.

Subjects and methods

Four voluntary Caucasian female subjects (ages 60, 56, 65 and51 years) who presented with a wish for nonsurgical facialrejuvenation were included in this study (Table 1). None ofthe individuals had a history of prior facial surgery, trauma,notable comorbidity or prior filler injections less than 1 yearbefore the start of the study. All participants signed informedconsent forms and paid a symbolic treatment fee, which wasrefunded after completion of the six-month follow-up. Thestudy medication was supplied by Merz Pharmaceuticals freeof charge, as well as a financial support for the 3Dcalculations.

Prior to injections, the individuals underwent standardphotograph series and three-dimensional surface scanning.Scanning was performed using an Artec MHT surface scanner(Artec Group, San Diego, California), which uses structuredlight technology. A flashing light projects a grid pattern ontothe scanned surface, and the distortion of this grid is capturedby three cameras from different angles. The subjects werescanned in the sitting and supine position with teeth inocclusion without forced bite, lips closed, eyes opened andwith forward gaze and without activation of the mimic mus-culature. The Frankfort horizontal was used as a referenceplane and the head adjusted to align it horizontally andvertically.

All injections of CaHA (RADIESSE™, Merz PharmaceuticalsGmbH, Frankfurt am Main) were performed by a single sur-geon (MM). The injections of CaHA in the cheekbone area andthe mandibular area were administered with a sharp needlesupraperiostally as a single bolus. The other regions wereinfiltrated with an atraumatic needle in the deep dermal layer.Following the administration, the

product was massaged in the different regions in order toprevent irregularities. The volumes injected per region foreach patient are given in Table 2.

The measurements were repeated directly following theinjections, as well as after 2 weeks and after 6 months. At 2weeks and 6 months, the participants were additionally askedto fill out a questionnaire assaying their satisfaction and thepain level during the injections, each on a scale from 1 (best)to 6 (worst).They were also questioned whether they wouldrepeat the procedure and whether they would recommend itto their best friend (yes/no). The patient’s weight wasrecorded at all time points.

Registration

To establish an initial spatial reference between the surfacescans, seven landmarks were placed manually on each scan(endocanthion, ectocanthion, pronasale and labial commis-sures). Based on these references, a generic facial model wasaligned rigidly, and subsequently matched onto each of thescans by applying rigid, affine and elastic iterative closestpoint (ICP) registration algorithms by using the R-packagemesheR (https://github.com/zarquon42b/mesheR). As aresult, all surface scans can be represented by a surface meshwith quasi-homologuous vertices.

In order to find variation within the cheek region, wedefined a T-shaped region on the template (forehead/nose),which was unaffected by the injections (Figure 1A). Based onthe correspondence between all vertices, this region was iden-tified in all surface scans and used to register the scans of eachpatient rigidly onto the corresponding pre-OP state. Thisallows for an analysis of changes between the aligned surfaces.

ROI

As region of interest (ROI), we defined an area on the leftcheek that spanned the treatment area in all patients(Figure 1B). As all vertices are corresponding between scans,the ROI could be extracted consistently for all scans of allpatients involved.

Table 1. Demographic data and patient satisfaction.

Patient 1 2 3

Age (at time of treatment) 60 56 65Complications (self-reported) Swelling and ecchymosis

of the pre-jowl area for 1week

2 weeksSatisfaction (grade) 3 1 2Would repeat treatment (yes/no) Yes Yes NoWould recommend to best friend

(yes/no)Yes Yes No

Pain (grade) 5 2–1 46 monthsSatisfaction (grade) 2 1 3Would repeat treatment (yes/no) Yes Yes NoWould recommend to best friend

(yes/no)Yes Yes No

Pain (grade) 5 2 6

Notes: Grades: 1 – best, 6 – worst.

Table 2. Amounts of Radiesse injected per region (amount used on each side inml, except when otherwise indicated).

Patient 1 2 3 (right/left)

Infraorbital 0.5 0.25 0.3/0.25Maxillary 0.5 0.25 0.3/0.5Nasolabial fold 1.8 0.3 1.5/0.25Cheek 5.5/4.5Marionette lines 0.4 0.4 0.4/0.5Jowl region 0.3 0.3 0.3/0.3Total 3.5 1.5 8.3/6.3

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Distance measure

All vertices within the ROI were projected orthogonally, i.e.along their normal vectors, onto from the pre-OP state to thepost-OP states. As a metric for changes in distances relating tothe pre-OP state, we chose the average distance between theoriginal position of the vertices and these projections.

Volume measurement

To obtain volume changes of an open mesh, we defined thevolume between two states as the volume confined by thesurfaces of the ROI in the pre-OP state and its orthogonal

projection, with the borders simply closed by connecting theborder vertices (Figure 1C).

Results

All four patients completed the study without complications.In particular, there were no signs of allergic reaction, nodulesor otherwise palpable foreign material. Patient 2 reportedswelling and ecchymosis of the pre-jowl area, which resolvedspontaneously after 1 week. There were no relevant weightchanges (>±1 kg) in any of the patients. Unfortunately,patient 4 had to be excluded because of defective pre-injection3D scans, which did not allow us to perform measurements.

A B C

Figure 1. (A) Conservative (unchanged) surface area of facial 3D scans used for registration of scans. (B) Examined area of interest. (C) Illustration of measuredvolume between pre- and post-facial surface.

B DCA

H

I J K L

E F G

Figure 2. Case 1 (60 y.o.) is shown prior to injections (A and E), immediately following the injections (B and F), after 2 weeks (C and G) and after 6 months (D and H).0.55 ml were injected into the tear trough, 1.25 ml into the nasolabial fold, 1 ml to the midface and zygomatic region and 0.7 to the pre-jowl area, totaling in aninjection volume of 3.5 ml per side. (I) color coding of the heatmaps showing the changes directly post-injection (J), after 2 weeks (K) and after 6 months (L), eachcompared to pre-injection.

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After 2 weeks, satisfaction rates were 3, 1 and 2, and after 6months 2, 1 and 3, respectively. Participants 1 and 2 statedthey would repeat the treatment and recommend it to theirbest friend, whereas participant 3 would do neither. Painduring treatment was graded as 5, 2–1 and 4 after 2 weeks,and 5, 2 and 6 after 6 months (Table 2).

Figures 2–4 show the results after the injections withCaHA in patients 1, 2 and 3, respectively. In these figures,panels A and E were taken prior to injections, and B and Fimmediately following the injections. Swelling and ecchymosisare noted in all cases. Panels C and G show the result after 2weeks, and D and H after 6 months. Panels I, J, K and Lrepresent the displacement of the facial surface vertically tothe surface in millimeters comparing pre-injection anddirectly post-injection (J), pre-injection to 2 weeks post-injec-tion (K) and pre-injection to 6 months (L). Panel I explainsthe color coding, which ranges from red and yellow (negative= pre-injection inside/less volume than post-injection) togreen (0, no change) to shades of blue (positive = pre-injec-tion outward displacement/more volume than post-injection).Time-lapse morphings of the heatmaps are shown as supple-mental digital content in videos 1, 2 and 3.

Increase in volume after the injections was documented inall participants. Case 1 exhibited a volume increase of 10.59

ml immediately following the injections, 2.78 ml after 2 weeksand 2.4 ml after 6 months. These values were 3.28, 0.66 and1.48 ml for case 2 and 14.23, 13.2 and 4.35 ml for case 3,respectively. An alternative method of quantifying the changesin soft tissue volume was to measure the mean surface dis-placement vertically toward the surface between the baselineand the post-injection time points. Using this method, dis-tances of 2 mm after injection, and 0.54 and 0.46 mm after 2weeks and 6 months, were measured in case 1. The respectivemeasurements were 0.42, 0.11 and 0.25 mm for case 2 and2.63, 2.39 and 0.8 mm for case 3 (Figure 5).

Discussion

The field of facial rejuvenation and aesthetic medicine ingeneral is still characterized by a lack of objective methodsof result quantification. Since the facial appearance is a highlysubjective matter, it is understandable that complete quanti-fication of aesthetic procedures can never be completelyachieved by numerical analysis. However, in times of evi-dence-based medicine, it is our belief that it should be possi-ble to quantify the results of the suggested procedure for acertain aspect of aging-related facial changes (e.g. volumeloss). Only when the methods to do so are established, it

ABCD

HE F G

I J K L

A B C D

G H

Figure 3. Case 2 (56 y. o.) is shown prior to injections (A and E), immediately following the injections (B and F), after 2 weeks (C and G) and after 6 months (D and H).0.25 ml CaHA was injected in the tear trough area, 0.25 ml in the premaxillary region, 0.3 ml in the nasolabial fold, 0.4 ml in the marionette lines and 0.3 ml toaugment the jowl area for a total of 1.5 ml. (I) color coding of the heatmaps showing the changes directly post-injection (J), after 2 weeks (K) and after 6 months (L),each compared to pre-injection.

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will be possible to compare results of different treatmentoptions. This in turn allows the physician and the patient toadopt the best suited treatment approach among the increas-ingly confusing landscape of products and proceduresavailable.

Descriptive reports of the aging face (16–18) and soundimaging studies of the changes of the facial skeleton (19,20)are numerous. During the recent years, several publications inthe field of orthodontics and maxillofacial surgery appearedexamining facial soft tissue changes in cleft palate, cleft lip andmalocclusion patients (21–25). Certainly, the complexity ofthe facial soft tissue architecture, with its multiple separate yetinteracting compartments, has made this task difficult. Othersand our group described three-dimensional surface scanningfor this purpose (12,13,15), which has to be seen as themethod of choice for quantification of facial soft tissue inter-ventions, yet the technical complexity still limits widespreadacceptance.

In this study, it was possible to quantify the effects ofCaHA injections for facial rejuvenation by describing thedistance of displacement between the skin surface beforeand after the injections as well as by calculating volumechanges in the region of interest. The detection of the facial

changes was facilitated by the fact that in two patients, largevolumes of CaHA (3.5 and 6.3/8.3 ml per side) were injected.Clinically, the volume restoring effect evidently persisted incases 1 and 3, yet the changes in subject 2 at 6 months are notclearly evident. However, even when using only 1.5 ml CaHAper side as in patient 2, it was possible to measure the changesusing 3D surface scanning technology, suggesting that thismethod of measurement is precise enough to even detectsmaller amounts of a filler material over longer periods,which is simply impossible with simple clinical examinationor comparison of 2D photographs. However, it has to bepointed out that although the used scanner has a resolutionof 0.5 mm and even minimal changes in the 3D texture can bedetected and measured, the technology is not without limita-tions. Even small alterations in the exact posture of theassessed subject like inclination of the head, activation ofmasticatory or mimic musculature or coverage with facialhair can lead to variations in the measurements, whosedimensions can possibly exceed those that are meant to bemeasured. The 2-week and 6-month results of subject 2 mightbe interpreted in that way (Figure 5), as the observed changesare higher after the longer period of time. The absolutedifference is not much, yet the trend that solely relies on

A B C D

E F G H

I J K L

Figure 4. Case 3 (65 y.o.) is shown prior to injections (A and E), immediately following the injections (B and F), after 2 weeks (C and G) and after 6 months (D and H).0.3 ml CaHA was injected to the right and 0.25 to the left tear trough area, 0.3 ml in the right and 0.5 ml in the left premaxillary region, 1.5 ml to the right and 0.25ml to the left nasolabial fold. 5.5 ml was injected to the right and 4.5 ml to the left cheek, 0.4 ml to the right and 0.5 ml to the left marionette lines and 0.3 ml to thejowl region, for a total of 8.3 ml on the right and 6.3 ml on the left. (I) color coding of the heatmaps showing the changes directly post-injection (J), after 2 weeks (K)and after 6 months (L), each compared to pre-injection.

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resorption would be expected to be the other way around ascan be shown in the other two subjects. On the other hand, itmight be possible that a postulated de novo synthesis ofcollagen might lead to the observed increase in volume inthis case in which the absolute injection volume is lower, andthis effect might become more evident. It is essential forstudies using high-resolution 3D imaging that exact studyprotocols are designed and followed to minimize inconsis-tency in the exact measurements.

Additionally, the post-interventional course over a period ofsix months could be followed up. It was shown that an augmen-tation effect is still measurable by this method after a six-monthperiod, which is in line with the literature on the duration ofeffect of CaHA injections. The measured sustainment of injectedvolume after 6 months varies from 68 to 99% to 30% in patients1–3, respectively. It seems to be lower for the higher volumeinjections. Ideally, in further studies, the duration of the follow-up should be extended until the changes return to the baselinelevels. Additionally, a more specific numeric quantification ofthe resorption process, which might in turn help in prospectivetreatment planning, requires further studies with more study

objects to evaluate individual trends like body fat or individualanatomy, the influence of the filler volume or predictions aboutspecific treatment localizations.

An advantage of the scanning system we use is that it is afully mobile unit, enabling the researcher to perform the scansin various positions. This is especially important for facial softtissue, since we previously showed that there is an increasedsoft tissue mobility between the upright and the supine posi-tions in older individuals (12). Ideally, a rejuvenation proce-dure should not only increase volume but also reverse theincreased soft tissue mobility seen in the older patient, aneffect we could not show for CaHA in this study (data notshown), yet the study design allows for such an approach.

Deep CaHA injections were generally tolerated well bythe patients. Patient 3 whished a maximal augmentativeeffect and received 6.3 ml injections to the right, and8.3 ml to the left side of the face. She consequentlycomplained of pain and reported that because of painand despite being satisfied with the result, she would nothave the procedure again and would not recommend it toher best friend. Possibly, several settings with repeated

A

B

Post injektionem 2 Weeks 6 Months0

5

10

15 Patient 1

Patient 2

Patient 3

Time

Vol

ume

chan

ge (

ml)

Post injektionem 2 Weeks 6 Months0

1

2

3

Time

Dis

tanc

e fr

om b

asel

ine

(mm

)

Figure 5. Bar charts indicating the changes of volume (A) and the orthogonal distance of displacement of the facial surface (B) relative to the pre-intervention statedirectly after injection, after two weeks and after six months.

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injections would be better suited in these cases, yet ourstudy design did not allow for this approach. Anotherpossibility to improve patient comfort would be to use amixture of calcium hydroxylapatite dermal filler mixedwith local anesthetic, as reported by Rauso et al. (26).

Because of its calcium component, concerns have beenraised about the interference of CaHA with bone imagingstudies of the face. These have been dissipated by the workof Carruthers et al. showing that the presence of thesubstance is indeed demonstrated in the soft tissue inplane radiographs and computer tomography images, butits appearance is distinct from the underlying bony struc-tures, which can be diagnostically evaluated (27). In thiswork, we did not perform diagnostic studies to investigatethe presence of the substance.

The purpose of this proof-of-principle study was to use three-dimensional surface scanning to quantify therapy-induced facialsoft tissue changes. To the best of our knowledge, this is the firststudy to achieve this for a facial aesthetic procedure using CaHA.It is worthwhile to design further, larger-scale studies in thisfashion to objectively measure the results of aesthetic interven-tions. It is possible to perform comparative studies, comparingthe effect of one procedure against another or longitudinalstudies, measuring the effects of a procedure over time. Wethus hope that a body of evidence can be accumulated whichassists the practitioner in counseling patients based on solidfacts, which should be the basis for every treatment modality.

Funding

The study was supported by Merz Pharmaceuticals.

Conflict of interest declaration

Dr Montanari has received allowances for working as clinical instructorfor Merz products. All the other authors declare that they have noconflicts of interest to disclose.

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