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Injectable facial fillers: imaging features, complications, and diagnostic pitfalls at MRI and PET CT

Injectable facial fillers: imaging features, complications, and diagnostic pitfalls at MRI and... Insights Imaging (2017) 8:557–572 DOI 10.1007/s13244-017-0575-0 REVIEW Injectable facial fillers: imaging features, complications, and diagnostic pitfalls at MRI and PET CT 1 1,2 1 3 Pravin Mundada & Romain Kohler & Sana Boudabbous & Laurence Toutous Trellu & 1 1 Alexandra Platon & Minerva Becker Received: 30 June 2017 /Revised: 2 September 2017 /Accepted: 5 September 2017 /Published online: 4 October 2017 The Author(s) 2017. This article is an open access publication Abstract Silicone has signature MRI features, calcium hydroxyapatite Injectable fillers are widely used for facial rejuvenation, correc- has characteristic calcifications, whereas other injectable fillers tion of disabling volumetric fat loss in HIV-associated facial have overlapping imaging features. Most fillers (hyaluronic ac- lipoatrophy, Romberg disease, and post-traumatic facial id, collagen, and polyalkylimide–polyacrylamide hydrogels) disfiguring. The purpose of this article is to acquaint the reader have signal intensity patterns compatible with high water con- with the anatomy of facial fat compartments, as well as with the tent. On PET-CT, most fillers show physiologic high FDG up- properties and key imaging features of commonly used facial take, which should not be confounded with pathology. Abscess, fillers, filler-related complications, interpretation pitfalls, and cellulitis,non-inflammatory nodules,and foreignbody granulo- dermatologic conditions mimicking filler-related complica- mas are the most common filler-related complications, and im- tions. The distribution of facial fillers is characteristic and de- aging can help in the differential diagnosis. Diffusion weighted pends on the anatomy of the superficial fat compartments. imaging helps in detecting a malignant lesion masked by injected facial fillers. Awareness of imaging features of facial fillers and their complications helps to avoid misinterpretation of MRI, and PET-CTscans and facilitates therapeutic decisions * Minerva Becker in unclear clinical cases. Minerva.Becker@hcuge.ch Key points Pravin Mundada � Facial fillers are common incidental findings on MRI and Pravin.Mundada@hcuge.ch PET-CT scans. Romain Kohler � They have a characteristic appearance and typical anatomic romain.kohler@hopitalvs.ch distribution Sana Boudabbous � Although considered as safe, facial filler injections are as- Sana.Boudabbous@hcuge.ch sociated with several complications Laurence Toutous Trellu � As they may mask malignancy, knowledge of typical imaging Laurence.Trellu@hcuge.ch features is mandatory. Alexandra Platon � MRI is a problem-solving tool for unclear cases. Alexandra.Platon@hcuge.ch . . Keywords Injectable facial fillers Hyaluronic acid Division of Radiology, Department of Imaging and Medical . . . Silicone MRI PET-CT Granuloma Informatics, Geneva University Hospital, University of Geneva, Rue Gabrielle Perret Gentil 4, 1211 Geneva 14, Switzerland Present address: Division of Diagnostic and Interventional Abbreviations Radiology, Sion Hospital, Avenue du Grand-Champsec 80, CHA calcium hydroxyapatite 1951 Sion, Switzerland 3 CT computed tomography Division of Dermatology and Venerology, Department of Medical EC European Community Specialties, Geneva University Hospital, University of Geneva, Rue Gabrielle Perret Gentil 4, 1211 Geneva 14, Switzerland FBG foreign body granulomas 558 Insights Imaging (2017) 8:557–572 FDA Food and Drug Administration injection procedures and their complications to avoid misdi- FDG F - fluorodeoxy glucose agnosis and unnecessary biopsy. HA hyaluronic acid Tothebestofourknowledge,onlyveryfewarticleshavesofar HIV-LA HIV-associated facial lipoatropy dealt with the imaging features of injectable facial fillers [3, MRI magnetic resonance imaging 6–11]. The purpose of this article is to acquaint the reader with NIN non inflammatory nodule the anatomy of facial fat compartments, as well as with the prop- PAAG polyalkylimide - polyacrylamide hydrogels ertiesandimagingfeaturesofcommonlyused facialfillers,filler- PLLA poly-L-lactic acid related complications, interpretation pitfalls, and dermatologic PMMA polymethylmethacrylate conditions mimicking filler-related complications. PET-CT positron emission tomography CT SMAS superficial musculoaponeurotic system Imaging techniques Introduction Most often injectable facial fillers are detected incidentally on cross-sectional imaging studies. Therefore, radiologists need to be familiar with the imaging features of injectable fillers in "We are all of us stars, and we deserve to twinkle". order not to confound these with true pathology or vice-versa Marilyn Monroe in order not to miss true pathology obscured by filler injections. The number of people undergoing facial filler injections Patients with suspected filler-related complications are to get a youthful twinkle has strikingly increased in the last most often evaluated clinically and treated accordingly [12]. decade. In 2015, more than two million individuals in the Therefore, the reported use of cross-sectional imaging in this USA alone underwent hyaluronic acid (HA) injections of clinical setting is limited. Nevertheless, dermatologic condi- which the majority was for facial rejuvenation [1]. tions (cutaneous lymphoma, sarcoidosis, dermatomyositis) Although middle-aged women still constitute the majority, may present clinically with non-specific features and imaging it is not uncommon to see young adults and older people can help in differentiating these entities from filler-related undergo facial filler injections [2]. These injections, touted complications. The imaging requirements for the evaluation as safe and simple Blunch-time procedures,^ have become of the facial skin and subcutaneous tissues including facial an attractive alternative to incision-needing cosmetic surgery fillers vary according to the practicing centre. Depending on such as facelift procedures. Apart from the desire to look the availability, radiologists use MRI or high-frequency ultra- young, other indications include the correction of disabling sound to assess the location and volume of the injected facial volumetric soft tissue loss in HIV-associated facial fillers and to evaluate filler-related complications. At our in- lipoatrophy (HIV-LA), Romberg disease, and post-surgical stitute, MRI is the preferred modality due to its excellent soft and post-traumatic facial disfiguring [3–5]. tissue discrimination capability, large field of view, and ability The injection of dermal fillers gives desirable cosmetic to provide anatomic, quantitative, and functional information. outcome by erasing skin rhytides or restoring facial volume MRI has an excellent ability to detect soft tissue inflammation, loss, or both. The commonly injected sites on the face include abscess, and also foreign material in the soft tissues [13]. It is the perioral area, periocular region, nasolabial folds, malar fat preferred over ultrasound for the localisation of dislodged pad, marionette lines, glabella, and lips. The rising demand for fillers because it provides anatomical reference [2]. aesthetic procedures has led to the introduction of multiple At our institution, the MR examination protocol for facial injectable dermal fillers on the market. The actions by which fillers and dermatologic conditions includes high-resolution these fillers produce the desired cosmetic outcome differ from thin-slice (512 × 512 matrix for a field of view of 16-20 cm, each other and, thus, their complications and imaging features. 1-3 mm slices) acquisitions on a 1.5 or 3 Tesla MRI magnet A radiologist may be asked to evaluate the complications, with surface coils and parallel imaging techniques. We acquire extent, and location of a known facial filler injection. The the following sequences: T1 W (axial), T2 W ± fat saturation incidentally detected facial filler poses a diagnostic challenge or a STIR sequence (axial and coronal), diffusion weighted because the patient may forget, deny the history of filler injec- sequences with ADC maps (axial), and post gadolinium injec- tion, or may not know what type of filler was used [6]. It is a tion T1 W with fat saturation. If the injected filler is not reality of the world market of facial rejuvenation that facial known, a Bsilicone only^ sequence with simultaneous water filler injections are not only performed by qualified physi- and fat saturation (axial) before gadolinium injection should cians, but also by many unlicensed practitioners. It is impera- equally be obtained. A Bsilicone-only^ sequence is designed tive for the radiologist to remain abreast with the commonly to suppress all tissues except silicone. It is a combination of inversion recovery–turbospinecho(IR-TSE)withaTI used injectable facial fillers, the anatomical context of Insights Imaging (2017) 8:557–572 559 chosen to suppress fat signal (TI = 230 ms) and a spectrally superficial and deep fat layers separated by the superficial selective pre-pulse, which suppresses water [14]. Although musculoaponeurotic system (SMAS). The SMAS is a three- widely used to image patients with silicone breast implants, dimensional fibrous network that connects the periosteum, the the sequence is rarely obtained in other parts of the body. For muscles of facial expression, the platysma, and the fascia of the detection of injected silicone in the face, the sequence the parotid gland with the dermis [20]. The superficial fat layer parameters at 3 T MRI that are used in our institution are as (located superficial to the SMAS) was long considered a sin- follows: TR = 7.8 ms, TE = 3.69 ms, TI = 230 ms, flip gle confluent mass, and treatments were designed to lift and angle = 20 deg., voxel size = 1.5 × 1.5 × 6.0 mm, one average, reposition the fat pad as one single unit [21]. Similarly, prac- six concatenations. We equally recommend inclusion of a titioners injected facial fillers in arbitrarily defined facial com- DWI sequence in the protocol for two reasons. First, DWI partments [21]. More recently, Gosai et al. were the first to helps in detecting a malignant lesion masked by injected facial classify the superficial facial fat into medial and lateral com- fillers [15]. Second, DWI discriminates between a frank ab- partments (units) based on their relationship with the underly- scess and inflammation and, thus, helps in avoiding futile ing muscles of facial expression on MRI [22]. Rohrich and attempts of percutaneous aspiration [13]. Pessa demonstrated the actual anatomical divisions of the fa- High-frequency ultrasound is a safe, cost-effective, and wide- cial fat by injecting methylene blue dye into cadaveric facial ly available modality for the evaluation of facial fillers. Various specimen [23]. Subsequent studies by Rohrich et al. and other studies have documented its ability to localise commonly used groups validated the anatomical division of the facial fat and facial fillers. Ultrasound has also been useful to detect filler- also identified additional distinct compartments [24–28]. In related complications, such as abscessesorgranulomaslocalised 2012, Girrloff et al. quantified various facial fat compartments in the superficial fat spaces. In cases with suspected deep spread on CT scans after injecting iodinated contrast in a cadaveric of infection, MRI or contrast-enhanced CT (in the emergency facial specimen [29]. setting) is, however, necessary. Operator dependability and poor The superficial fat compartments (between the dermis and reproducibility remain major shortcomings of ultrasound in the the SMAS) and the deep fat compartments (between the evaluation of facial fillers [16–19]. SMAS and the periosteum of the facial bones) are illustrated CT does not offer advantages over MRI. However, it can in Figs. 2 and 3. These fat compartments are separated from identify calcifications, which are a hallmark of certain fillers each other by fibrous membranes, which carry perforator ves- and filler-related complications (see below). To reduce the sels. Schaverien et al. suggested that the highly organised radiation exposure, cone beam CT (CBCT) can be used as anatomical arrangement of the facial fat and the associated an alternative to CT to identify calcifications. However, vasculature are probably related to the embryologic develop- CBCT does not allow assessment of soft tissues. Therefore, ment of the facial musculature [30]. contrast-enhanced CT is preferred whenever infectious com- Facial fat in these compartments age differently plications are suspected. (hypotrophic versus hypertrophic changes or ptosis). For ex- F18- fluorodeoxyglucose (FDG) positron emission ample, ageing causes hypertrophic ptotic changes in the tomography-CT (PET-CT) has been found useful for the de- nasolabial fat and middle cheek fat, and hypotrophic involu- tection of the source of infection/ inflammation in the body tion in the lateral temporal cheek fat and deep medial cheek ahead of morphological changes. FDG PET-CT is increasing- fat, respectively. In patients with HIV-LA, substantial volu- ly used in the evaluation of fever of unknown origin, large metric changes of the superficial fat compartments vessel vasculitis, complicated sarcoidosis, osteomyelitis, HIV- (nasolabial, medial and middle superficial cheek fat) occur, related infections, and infections in the immunocompromised. whereas deep facial fat units appear to be less affected [31]. However, the use of FDG PET-CT is not recommended for the Therefore, qualitative assessment of these compartments plays evaluation of injectable facial fillers as increased FDG uptake an important role in facial rejuvenation methods and, in par- is non-specific and can be seen both in patients with and ticular, in deciding which fat compartments should be without complications caused by injectable fillers [11]. The volumised [32, 33]. Knowledge of facial fat compartments increased FDG uptake associated with injectable fillers is a may also help in understanding facial filler distribution and typical pitfall (Fig. 1), which may mimic a malignant tumour migration. or an infectious process depending on the clinical situation. Because of its high soft tissue resolution, MRI is excellent- ly suited to depict the facial fat units. Their relative position with respect to the SMAS, orbit and facial skeleton allows Imaging-relevant anatomy of facial fat correct identification of individual compartments (Fig. 3). compartments Nevertheless, the tiny fibrous septae that separate these com- partments, as well as the supporting ligaments of the face Traditionally, surgeons performing facial rejuvenation injec- cannot be seen on routine high-resolution MR images obtain- ed with standard coils. tions and cosmetic surgeries divided the facial fat into the 560 Insights Imaging (2017) 8:557–572 Fig. 1 45-year-old female patient evaluated with PET-CT for lymphoma on CT (arrows in b) and hardly enhancing on post-gadolinium T1 W fat staging. Coronal PET-CT image (a) reveals incidentally detected FDG saturated sequences (c, arrows). The patient had a history of silicone avid areas in bilateral nasolabial fat compartments (arrows). injections four years earlier. She had no filler-related symptoms SUVmean = 4.6, SUVmax = 5.9. The areas appear mildly hyperdense Types of facial fillers and normal imaging features (<24 months), and permanent. Rapidly resorbable fillers include HA, collagen and autologous fat. Slowly resorbable fillers in- The Food and Drug Administration (FDA) of the USA considers clude PLLA, CHA and dextran, whereas permanent fillers in- injectable facial fillers as medical devices used to improve ap- cludeliquidsiliconeandPMMA[36].Siliconeisthemostwidely pearance and without health benefit [34]. The classifications of used non-resorbable synthetic substance for medical purposes. injectable facial fillers vary according to their properties such as Of the three forms of silicone, only the liquid silicone is used as natureofthefiller,timeintervalforitsbiodegradation,andwheth- facialfillerwhiletheelastomerandgelareusedinbreastimplants er it is composed of one or more materials [35, 36]. The filler can [37, 38]. The FDA and the European Community (EC) do not beautologous,biological,orsynthetic.Autologousfillersconsist recommend all commercially available products. While some of the patient’s own body fat. Biological fillers consist of either products may be FDA approved, they are not EC approved and collagen of bovine, porcine, or human origin or hyaluronic acid vice-versa [39, 40]. Besides, some products have a limited ap- (HA) of bacterial origin. Synthetic fillers include paraffin, sili- proval, which limits their use to the specified areas in the face. cone, calcium hydroxyapatite (CHA), polymethylmethacrylate (PMMA) microspheres, polyacrylamide hydrogel, Autologous fat fillers hydroxyethyl/ethyl methacrylate, and poly-L-lactic acid (PLLA) [36]. Based on biodegradation features, fillers can be Autologous fat was one of the earliest used injectable fillers to classified as rapidly resorbable (<12 months), slowly resorbable reconstruct facial scars [41]. Its use has declined over the years Fig. 2 Schematic illustration of the subcutaneous facial fat cheek fat (4), the central forehead fat (5) and paramedian forehead (6) compartments. 3D reconstruction from contrast enhanced CT. Position fat, the superior orbital (7), inferior orbital (8) and lateral orbital (9) fat, of the retaining ligaments of the face (white lines), superficial (yellow), and the superior jowl (10) and inferior jowl (11) fat. b The deep group and deep (light green) fat compartments in relationship to the facial (light green) includes the following compartments: the medial (12) and skeleton. a The superficial group (yellow) includes the following lateral (13) sub-orbicularis oculi fat, the deep medial cheek fat (14), the compartments (units): the nasolabial fat (1), the medial superficial buccal fat pad (15) and Ristov’s space (16). Modified after Rohrich et al. cheek fat (2), the middle superficial cheek fat (3), the lateral temporal and Alghoul et al. [23, 83] Insights Imaging (2017) 8:557–572 561 inferior jowl fat (11), medial sub-orbicularis oculi fat (12), deep medial Fig. 3 Facial fat compartments as depicted by routine MRI. a – d. Axial T2 W slices. e. Sagittal T2 W image through the mid-pupillar line. f – g. cheek fat (14), buccal fat pad (15). Muscles and other relevant structures: Coronal T2 W slices. For easier correlation with the schematic drawing depressor anguli oris muscle (DAOM), frontalis muscle (FM), levator shown in fig. 1, the same numbers were used for the superficial and deep labii superioris and levator labii superioris aleque nasi muscles (LLSM), facial fat compartments. Fat compartments: nasolabial fat (1), medial platysma muscle (PM), orbicularis oculi muscle (OOCM), orbicularis oris superficial cheek fat (2), middle superficial cheek fat (3), lateral muscle (OOM), superficial musculoaponeurotic system (SMAS), temporal cheek fat (4), paramedian forehead fat (6), superior orbital fat Stensen’s duct (SD), zygomaticus minor and major muscles (ZM) (7), inferior orbital fat (8), lateral orbital fat (9), superior jowl fat (10), due to inconsistent resorption rates, which vary from months often has a streaky appearance [6]. The imaging appearance of to years. However, autologous fat is regaining popularity in collagen may change if mixed with other substances to pro- some parts of the world due to improved harvesting tech- long its cosmetic effect. niques [41–43]. On CT, the filler appears as low attenuation soft tissue. On MRI, it follows fat signal on all sequences and Calcium hydroxyapatite (CHA) fillers may show a thin pseudocapsule (Fig. 4). CHA (Radiesse) comprises spherical microparticles of bone- Collagen fillers like composition suspended in an aqueous sodium carboxymethyl cellulose gel. Marionette lines and nasolabial Collagen is a major structural component of healthy skin. folds have been successfully corrected with CHA. The filler Bovine collagen was the first FDA-approved injectable der- has a tendency to nodule formation and foreign-body reaction, mal filler in the USA. The subsequently developed human which discourages its use for lip augmentation. The micropar- bio-engineered and porcine collagens gained popularity due ticles disintegrate over time, and the volumising effect may to low risk of hypersensitivity reactions as compared to their last for 1 to 2 years [9, 45]. However, the persisting soft tissue bovine predecessor. Collagen fillers may last from 6 to volume gain even after complete filler resorption implies 12 months, whereas collagen mixed PMMA microspheres in vivo de novo collagen formation [46, 47]. (Artefill) may last up to 5 years [6, 44]. On MRI, collagen CHA is hyperattenuating (HU 280-700) on CT and pre- appears hypointense on T1 W images and hyperintense on sents with well-defined linear streaks or rounded masses T2 W and STIR images (Fig. 5) due to its high water content (Fig. 5). CT filler density diminishes after 12 months as the [6, 8]. Collagen deposits may show minimal peripheral en- microspheres get absorbed, and eventually the filler may dis- hancement in the first 2 months of injection. This minimal appear after 24 months [9, 46]. On MRI, CHA fillers have low enhancement is not indicative of infection. On CT, collagen to intermediate signal intensity on T1 W and T2 W images. fillers show fluid attenuation and the injected subcutaneous fat They show mild post-contrast enhancement due to 562 Insights Imaging (2017) 8:557–572 Fig. 4 61-year-old woman with discrete facial asymmetry and induration Patient confirmed autologous fat filler injection nine months back. The of the left cheek. She had internal fixation of a left tetrapod facial fracture hypointense rim around the filler deposit on T2 and the post-gadolinium 25 years back. MRI showed a well-circumscribed lesion, isointense to fat rim enhancement on T1 represent a fibrous pseudo-capsule due to scar on T2 W (a) and post-gadolinium T1 W fat saturated (b) sequences (long tissue formation: dashed short arrow in (a) and short arrow in (b) arrows). The lesion is located in the left superficial medial cheek fat. vascularisation of the calcified matrix [9, 48]. On FDG PET- incidentally, warrants correlation with patient history and mor- CT, CHA appears strongly FDG-avid, which, if detected phological imaging to avoid misdiagnosis [9]. Fig. 5 Commonly injected facial fat compartments and characteristic labii superioris aleque nasii, and zygomaticus minor muscles). c 64-year- aspect of various fillers at MRI and CBCT. In all presented cases, the old man with HIV-LA and HA injection 6 months earlier. Axial STIR patients were symptom-free and were imaged for other reasons. a 55- image reveals HA injection performed in the deep medial compartment year-old woman with collagen filler injections 5 months previously. On (short arrows) and buccal fat pad (large arrow). d 45-year-old woman coronal STIR image, collagen filler injections in the superior (dashed with bilateral HA injections. On coronal STIR image, HA is detected in arrows) and inferior (arrows) jowl compartments are seen as hyperin- inferior orbital compartments (short arrows) and nasolabial fat compart- tense, lobulated and reticulated areas. Asterisks indicate large artefacts ments (long arrows). e and f 60-year-old woman with bilateral HA injec- due to dental implants. b 62-year-old woman with CHA injections 3 years tions for cosmetic purposes. On coronal STIR image (e), HA injection of previously. On axial CBCT with bone window settings, streaky calcific the superior (dashed arrow) and inferior jowl compartments (arrow). density of CHA filler is seen in the left and right medial and middle Sagittal T1 W image (f) shows hypointense HA in the nasolabial fat (short superficial cheek compartments (arrows) and extending towards the left arrow), medial superficial cheek compartment (dashed arrow) and jowl lateral temporal cheek fat (short arrow). Thin dashed arrows point at the compartment (arrow). Non-injected buccal fat compartment (asterisk) SMAS and muscles of facial expression (levator labii superioris, levator Insights Imaging (2017) 8:557–572 563 Hyaluronic acid (HA) fillers attenuation on CT [6, 10, 47]. On FDG PET CT, there is increased uptake due to the filler-induced subclinical inflam- HA is a naturally occurring polysaccharide in healthy soft mation [58]. tissue, which binds the collagen and elastic fibres to provide intercellular stability. The naturally occurring HA has a very Polyalkylimide and polyacrylamide hydrogels (PAAG) short half-life. Pre-processing and cross-linking prolong the half-life of HA before its use as filler [43, 49]. Depending PAAG (Bi o-Alcamid = polyalkylim ide and on cross-linking HA fillers can be divided into cohesive Aquamid = polyacrylamide) are non-biodegradable injectable (monophasic) or non-cohesive (biphasic) gels. The cohesive hydrogel polymers. Aquamid comprises 2.5-4.5% crosslinked gel disperses diffusely to fill the small gaps between collagen polyacrylamide hydrogel and 97.5-95.5% purified water [35, and elastin bundles, whereas the non-cohesive gel deposits in 59]. PAAG induces accumulation of fibroblasts and macro- puddles [44, 50]. The injected HA combines with natural HA phages, and formation of a fibrous capsule [35]. Correcting in the soft tissue, binds water due to its hygroscopic nature and nasolabial fold, facial contouring, rhytides, and facial also induces new collagen formation. Thus, a volume is cre- lipoatrophy by PAAG injection is approved in many coun- ated, which may last for a few months to 1 year [51–53]. HA tries. Delayed reactions like infection, granuloma and migra- fillers are the most widely used fillers for their safety, easy tion have been reported [60]. All abscesses reported in a study reversibility, and minimal side effects. occurred after polyalkylimide gel [2]. In analogy to other MRI with T2 W and contrast-enhanced T1 W sequences fillers containing large amounts of water, PAAG fillers appear can accurately assess the volumetric and temporal changes of hyperintense on T2 Wand hypointense on T1 W sequences [2, subdermal HA filler injection [3, 54]. Because of its high 61] and reveal no post-contrast enhancement. On CT, PAAG water content, HA filler appears strongly hyperintense on appears as a well-defined area of fluid attenuation. T2 W and STIR sequences and hypointense on T1 W se- quences. Injected HA typically shows well-defined serpigi- nous margins at imaging (Fig. 5). Minor post contrast en- Silicone oil filler hancement is seen in the initial 6 months of injection, which represents increased vascularisation of injected tissue. This Silicone is a permanent filler, which restores volume and in- minor enhancement and the signal intensity on T2 W images duces new collagen formation. The pure silicone oil is consid- gradually decrease during the first year after injection [3]. The ered inert, minimally antigenic, non-carcinogenic, and a poor volume gain after HA filler injection is maximal in the first medium for bacterial growth [62]. Its use as a tissue filler month and remains more or less stable for the next 12 months. became controversial due to the reported high rate of compli- Using 3D fat-saturated T2 W sequences, HA was found in cations. Many authors attribute the silicone injection-related anatomical regions situated much deeper than the compart- complications to the poor injection technique, use of industrial ment of the initial injection [3]. The hydrophilic nature of silicone and large volume injections [62, 63]. The off-label use HA and the diffusion permeability of the fibrous septae be- of FDA/CE approved silicone products as facial fillers with tween the facial fat compartments are thought to be responsi- microdroplet techniques is reported to have minimal side ef- ble for this finding [3]. As HA binds water in vivo and as the fects [62, 63]. Illicit silicone oil, however, continues to be in filler also induces in vivo procollagen formation (which has use as facial filler in many parts of the world despite high water content), MRI actually depicts a mixture of all complications. three substances (injected HA, bound water, and de novo The MRI appearance of silicon facial fillers varies accord- formed procollagen) and differentiation between these three ing to viscosity and purity. The low viscosity silicone oil is components is not possible with MRI [3]. On CT, HA fillers slightly hyperintense to water on T1 W images, iso- or slightly appear as areas of soft tissue attenuation. On PET-CT, they are hypointense to water on T2 W images, and hyperintense on occasionally FDG-avid [55]. the Bsilicone only^ sequence. High viscosity silicone oil is hypointense on T2 W images [6, 10]. A Bsilicone-only^ se- Poly-l-lactic acid (PLLA) quence is designed to suppress all tissues except silicone [14] (Fig. 6). On fat-saturated T1 W images silicone may appear PLLA (Sculptra), a biodegradable synthetic polymer hyperintense and show chemical shift artefact [64]. Post con- suspended in sodium carboxymethylcellulose and mannitol trast fat-saturated TIW images may show variable enhance- has been used for the treatment of HIV-LA and the correction ment depending on the inflammatory or reactive changes in of rhytides [56]. It induces subclinical inflammation with col- the surrounding tissues. On CT, silicone appears slightly lagen formation and fibrosis [57]. It has a gradual onset of hyperdense [6]. On ultrasound, it shows a hyperechoic action and results last for a few years [56]. PLLA appears Bsnowstorm^ appearance, which obscures soft tissue details hypointense on T2 W images and shows soft tissue [17–19]. 564 Insights Imaging (2017) 8:557–572 Fig. 6 Two different patients with filler injections performed under (arrows in b, e) suggesting an inflammatory reaction. However, in patient unclear circumstances (patient 1, 53-year-old woman, a-c; patient 2, 46- 1, the injected areas appear hypointense on the silicone only sequence year-old woman, d-f) developed diffuse swelling and induration of the (arrows in c), whereas in patient 2 the injected areas appear strongly lips and cheeks 1 year after the respective procedures. The injected filler hyperintense. Based on these images, the diagnosis of granuloma was a mixture of CHA and collagen in patient 1, and it was not known in formation due to CHA and collagen in patient 1 and due to silicone oil patient 2. In both patients, the filler and the resulting soft tissue changes in patient 2 was made. Biopsy obtained in both patients confirmed the show intermediate-to-low signal intensity on T2 W images (arrows in a, radiologic diagnosis, in particular biopsy also confirmed the presence of d), and nodular and strong enhancement on postgadolinium T1 W images silicone with a characteristic Swiss cheese pattern at histology Autologous fibroblasts and non-complicated facial fillers in 100% of patients [2, 8, 10].Accordingtothesestudies, MRI could detect injected Tissue harvested from the postauricular area is cultured to pro- fillers as small as 2 mm in diameter [10], and also those duce fibroblasts cell lines. These fibroblasts are injected intrader- filler-related abscesses and granulomas missed on clinical mally to correct dermal depressions and rhytides. Autologuous examination [2]. fibroblasts increase thickness and density of dermal collagen. Regarding filler characterisation, Tal et al. have claimed They have a low incidence of hypersensitivity [35, 44]. that they could accurately differentiate between the indi- vidual types of injected fillers on the basis of their signa- Paraffin ture MRI features [8]. The existing literature and experi- ence at our institution do not support their assertions. As Paraffin was perhaps the first substance to be used as facial discussed in the previous section, most facial fillers (HA, filler and caused severe granulomatous reactions and collagen, and PAAG) have a similar appearance on MRI Bparaffinoma formation^ [65]. CT features of Bparaffinoma^ due to their high water content [3, 6, 10]. In our experi- include calcific rounded foci and soft tissue density nodules ence, only silicone fillers have a characteristic MRI appear- with a calcific rim [7]. ance on the Bsilicone only^ sequence. The Bsilicone only^ sequence is, however, prone to artefacts from non- homogenous fat and water saturation, especially in the Role of imaging for filler detection presence of dental implants. Therefore, experience and and characterisation caution are required for its interpretation. CHA shows characteristic linear or clumps of calcifications The detection of injected facial fillers is straightforward on CT [46], whereas all other filler types do not show calcifi- with cross-sectional imaging provided radiologists are cations unless the injected filler causes foreign body reaction. aware of the typical injection sites (Figs. 1, 2, 3, 4, 5,and Foreign body granulomas (FBGs) induced by liquid silicone 6) and of MRI/CT features. Earlier published studies have or paraffin have typical eggshell, rounded, or nodular calcifi- demonstrated the ability of MRI in locating all complicated cations [7, 11]. Insights Imaging (2017) 8:557–572 565 Complications of facial filler injections and role Most complications like erythema, bruising and hypersen- of imaging sitivity do not require radiological evaluation. Non- erythematous nodules formed soon after injection are caused Notwithstanding the much-touted minimally invasive nature by the uneven distribution of the filler and are likely to resolve of facial filler injection procedures and safety claims of filler spontaneously. Even the nodules caused by inflammation/ manufacturers, all types of injectable facial fillers can cause infection may resolve spontaneously [66]. In one study in- short-term and long-term complications [38, 40, 66, 67]. volving PLLA injection in HIV-LA, patients showed small Short-term complications are usually related to the procedure palpable, painless nodules in 44% cases. Most of these nod- itself and early host response to the injected material. Early com- ules resolved spontaneously [74]. plications occur within days or weeks of the injection procedure and manifest clinically with erythema, bruising, hyperthermia, Abscess formation swelling, hypersensitivity, nodule formation, and lumpiness in the injection area. They are due to over-injection or mal- The filler injection interrupts the natural barrier of the skin and distributionof thefiller,ortheyare causedby iatrogenic infection increases the possibility of infection. Injections performed by [66, 68]. Infection is rare and has been reported in <0.2% of a untrained hands and use of illicit products increase the risk of series of 1300 patients treated with PAAG; more recent publica- abscess formation. Kadouch et al. reported a high incidence of tionssuggestanoverallinfectionrateof0.04%[69,70].Infection abscess formation with PAAG [2]. Nevertheless, an abscess is mainly caused by inadequate skin disinfection. Infections with can occur with all types of filler injections. Like an abscess Staphylococcus epidermidis, Propionibacterium acnes, and anywhere else in the body, filler-related abscess appears as a nontuberculous mycobacteria (NTM) usually manifest early or lobulated fluid collection with rim enhancement and adjacent within 3-6 weeks after inoculation. However, delayed manifes- fat stranding on MRI (Fig. 8). On DWI, the abscess may show tations(monthstoyearslater)arenotexceptional(Fig.7)[70].As restricted diffusion [13]. Nevertheless, infected filler deposits NTM are known to exist in tap water, infection occurs when tap and infected fluid collections may show absent restriction on water contaminates the injection procedure [71]. DWI (Fig. 8). To avoid this pitfall, correlation with symptoms Occasionally, severe and acute complications like local soft and morphologic MR images is essential. tissue necrosis, blindness, and cerebral infarct may occur due to vascular occlusion [72, 73]. A retrospective study reported Non-inflammatory nodule (NIN) and foreign body acute blindness with glabella and nasolabial fold injection of granuloma (FBG) autologous fat in seven patients, HA in four patients and col- lagen in one patient, respectively [72]. FBG and a NIN differ on imaging and histopathology [75]. Long-term complications are related to the injected filler Differentiation between the two conditions is important as it itself and delayed host response. These complications include influences patient management [10]. A FBG is a non-allergic FBG, delayed manifestations of infection including abscess chronic granulomatous reaction that appears months to years formation, migration of filler, disfiguring nodules and scarring, after filler injection and grows very slowly. FBG can be mul- tissue necrosis and ulcer, and persistent discoloration [40, 66]. tiple and recurring. On histology, FBG has wide spaces Fig. 7 A 49-year-old woman developed bilateral painful facial swellings medial deep cheek fat and buccal fat pads. These areas display reticulated and redness of skin 4 months after bilateral facial injection of PAAG enhancement on post contrast fat saturated T1 W images (arrows in c) fillers. On MRI, ill-defined streaky areas of signal abnormalities, suggesting cellulitis/infection. Haematological investigations showed hyperintense on axial STIR (arrows in a) and iso- to hypointense on raised inflammatory markers. Patient responded to treatment with axial T1 W images (arrows in b), were seen in bilateral superior jowl antibiotics and medial superficial cheek fat compartments with extension to bilateral 566 Insights Imaging (2017) 8:557–572 Fig. 8 A 65-year-old woman developed pain, erythema, and bilateral seen on CT have a high protein content (hypo-isointense on T2 and T1). cheek swelling after 6 months of HA facial filler injections. a Contrast- On b1000 (e) and ADC map (f), these rim-enhancing lesions show enhanced CT shows bilateral Bgrape-like^ hypodense, rim-enhancing variable diffusivity (long arrows). ADC values were between 1.2 and −3 2 areas (long arrows) and solid appearing enhancing nodules (short 2× 10 mm /s. The solid lesions (short arrows)showstrong arrows) in the nasolabial fat, medial and middle superficial cheek fat enhancement on MRI and no restricted diffusivity. Surgery confirmed compartments. T2 W (b), T1 W (c), and fat-saturated gadolinium bilateral infected fluid collections and isolated FBG enhanced T1 W (d) images reveal that the rim-enhancing areas already between the foreign body particles, abundant macrophages, histopathology, and fillers with or without thin rim enhancement fibroblasts and giant cells. It shows finger-like projections in were non-inflammatory on histopathology. Kadouch et al. did not adjacent tissues. Although all types of injectable fillers cause dwellondifferentiatingFBGfromnon-granulomatousinflamma- FBG formation, FBG is most often seen after long-standing tory changes. In our experience, FBGs show enhancement on silicone oil injection (Bsiliconoma^, especiallywithnonmed- MRI; however, the degree of enhancement may vary (Figs. 6, 8, ical grade silicone), whereas fillers such as HA have a low 9,and 10). As suggested by Giorlamo et al., nodular or diffuse FBG incidence. FBG shows three histological types: cystic, enhancement typically suggests FBG, whereas streaky enhance- lipomatous, and sclerotic. Discussion on the histological FBG ment in the subcutaneous fat corresponds to cellulitis (Fig. 9). On types is, however, beyond the scope of this article [39, 40, 76]. CT, FBGs may show punctate or eggshell classifications [6, 39, NINsare singlelumpsthatusuallyappear1to2monthsaftera 40] and on PET-CT, FBGs show high FDG uptake (Fig. 10). technically erroneous superficial facial filler injection. They oc- According to Kadouch et al. [2], clinico-radiologic agree- cur more often after injections of non-resorbable than resorbable ment was substantial for fillers without complications and fillers. In patients with HIV-LA, NINs can be seen years after non-inflammatory nodules (85%), moderate for abscesses PLLA injection. NINs are usually evenly sized, appear harder (60%), fair for low-grade inflammation (32%), and slight for and whiter than granulomas, and remain stable. On histology, migration (9%). The patient population in the study of they show a dense cluster of foreign material, few macrophages, Kadouch et al. comprised patients with filler injections either occasional giant cells, and a fibrous pseudo-capsule [39, 40, 76]. for cosmetic reasons or treatment of HIV-LA [2]. In our prac- The MRI features of FBG (Figs. 6, 8, 9,and 10) are described tice, regular use of MRI makes decision-altering contributions differently in the literature [77, 78]. Girolamo et al. have demon- to the evaluation of filler-related complications and in patients strated 100% correlation between the post-contrast enhancement with both head-neck cancer and fillers. Thus, the utility of around the complicated filler and histological evidence of granu- MRI for the assessment of filler-related complications might loma formation, whereas non-granulomatous inflammation did differ in a different set of patients and, also, according to the not show enhancement [10]. Contrary to this, Tal et al. observed clinical expertise. Nevertheless, the high cost of MRI warrants that histologically proven granulomas (n = 4) did not show post- its judicious use [10, 79]. contrast enhancement on MRI [8]. According to Kadouch et al., According to the literature, FBG is usually treated with complicated fillers with rim enhancement and adjacent fat intralesional corticosteroid injection, systemic steroid therapy stranding (n = 11) corresponded to inflammatory nodules on and, occasionally, surgical excision. NIN requires surgical Insights Imaging (2017) 8:557–572 567 Fig. 9 A 57-year-old woman with a remote history of collagen filler (short black arrow in b) and left SMAS (arrowhead) appear iso- injections developed facial lumps. Histologically proven FBGs (dashed hypointense on T1 W and hypointense on STIR images. On coronal arrows) in the right and left jowl fat units have high signal intensity on post gadolinium fat saturated T1 W image, the degree of enhancement STIR (a), low signal intensity on T1 W image (b), and strong of FBG (dashed arrows in c) and of fibrosis around FBG (short arrows in enhancement on fat saturated T1 W (c). The fibrosis around the c) appear similar and cannot be differentiated for each other on the basis granuloma (short white arrows in a, b) and the thickened right SMAS of enhancement alone excision and does not respond to intralesional or systemic migrate through lymphatic or haematogenous routes and may steroid therapy. mimic a malignant pathology of distant organs or granuloma- tous skin conditions [62, 66, 80]. Authors have showed that MRI was able to detect migrated facial fillers even in the Migration of fillers and overfilling absence of clinical suspicion and denial of a history of filler injection [2, 11]. Filler migration is a common indication for evaluation with MRI. Poor injection technique has been thought to cause filler Overfilling due to excessive filler injection can cause serious patient dissatisfaction. The incidence of overfilling migration. Although migration is not typical of any particular filler, permanent fillers (typically silicone) are more likely to varies from 0.8 to 8% of cases. It may appear as a focal lump or diffuse facial asymmetry. Overfilling due to HA migrate due to their longer presence in the body. They may Fig. 10 66-year-old woman with PET CT for fever of unknown origin. Palpable indurations of the nasolabial folds. FDG avid areas in bilateral nasolabial folds (arrows in a)appear of intermediate signal intensity on T2 W (b), isointense on T1 W (c), and homogenously enhancing on post-gadolinium T1 W fat satu- rated (d)sequences (arrows). The location of this signal abnormality prompts the diagnosis of previ- ously injected facial filler. Histopathology showed FBG due to probably PLLA facial filler injections 568 Insights Imaging (2017) 8:557–572 Fig. 11 75-year-old woman with unknown facial filler injections eight saturated contrast enhanced T1 W image (dashed arrows in c). It shows months back and left epiphora since one month. Coronal STIR (a)and restricted diffusion on the corresponding ADC map (arrow in d). coronal gadolinium enhanced fat saturated T1 W (b)images show the Furthermore, one would not expect filler injection in this location. sites of previous filler injections (short arrows) and an irregular mass in Initial histopathology showed evidence of an inflammatory nodule. the left lacrimal fossa with extension to nasolacrimal duct (dashed arrows Repeat biopsy, however, revealed squamous cell carcinoma of the in a and b). The spiculated, enhancing lesion well seen on the axial fat lacrimal sac injection can be reversed to some extent by injection of complicated silicone implants may or may not show silicone hyaluronidase. Needle aspiration and surgical excision contents on imaging [2, 6, 8]. mayalso be required[11]. Pitfalls in image interpretations Scarring and lymph node enlargement Facial fillers may pose a diagnostic dilemma for several rea- Severe chronic inflammatory thickening of the soft tissues sons. The patient may forget or deny the history of facial filler may cause significant disfiguring and subsequent scarring. injection due to social taboo. Injection performed by an unli- These reactions are common with permanent fillers, especially censed practitioner may be denied for medical insurance pur- silicone. CT/MRI may show a thick band-like subcutaneous pose. The patient may not know or remember the type of the deposition of silicone associated with diffuse soft tissue swell- injected filler. Incidentally detected or complicated facial filler ing and post-contrast enhancement (figure 6)[6, 62, 66]. Mild may mimic recurrent cancer on MRI in patients with previous enlargement of lymph nodes associated with facial fillers is head and neck cancer. Furthermore, facial filler injection may non-specific. The enlarged lymph nodes in case of mask a neoplasm (Fig. 11). Insights Imaging (2017) 8:557–572 569 Lack or denial of history may confuse filler-related com- cells, mainly macrophages [81]. The increased FDG uptake by plications with dermatological conditions including sarcoido- facial fillers may pose a diagnostic challenge in head and neck sis, dermatomyositis, and cutaneous lymphoma. On imaging, cancer and melanoma patients by mimicking a new primary or these dermatological conditions appear mildly hypointense on recurrence, especially if the injection is performed between T2 W images, may show restricted diffusion, and the involved two follow up scans and the history is denied or simply for- facial soft tissue compartments are atypical for filler injection gotten. Careful correlation with morphological imaging and (Fig. 12). An atypical anatomical location for facial filler in- the anatomical context of FDG uptake may help in avoiding jection or migration and restricted diffusion on DWI warrants unnecessary biopsy. histopathological correlation to exclude malignancy and other Although FDG CT/MRI is not an imaging modality of dermatological conditions. choice for the detection of filler-related complications, it is Uncomplicated facial fillers, FBG, non-granulomatous in- increasingly used for the detection of a source of infection flammation and abscess associated with facial fillers may and inflammation, sarcoidosis, and large vessel vasculitis. show increased uptake on FDG PET-CT/MRI. This uptake The increased cost of treating multi-drug resistant infections is attributed to increased glycolysis in activated inflammatory in immune-compromised patients, diabetics, and elderly Fig. 12 49-year-old woman presentingwithslowly progressing injection. Based on MRI features, the presumptive diagnosis of subcutaneous induration over the right cheek and with extension to the sarcoidosis, dermatomyositis, or cutaneous lymphoma was made and skin over the nose. Clinically, a facial filler injection related complication biopsy was recommended. Histopathology revealed sarcoidosis. was suspected as an underlying pathology. On MRI, the infiltrative lesion Subsequent CT of the chest (not shown) showed typical interstitial appeared hypointense on T2 W (arrows in a) and on T1 W images nodules and mediastinal lymphadenopathy. Retrospective analysis of (arrows in b) and showed avid enhancement on post contrast T1 W fat the head and neck MRI revealed no nodal involvement, in particular no saturated images (arrows in c, d). The lesion involves the superficial and Bdark lymph node sign^ [84]. Nevertheless, the nonenhancing dark deep layers of the facial fat and the SMAS. Note scattered rounded regions in c) corresponded histologically to sarcoid granulomas, the nonenhancing dark regions (dashed arrows) embedded in the strongly imaging features being strikingly similar to granulomas in nodes with enhancing cutaneous lesion in c) possibly suggesting granulomas. The the Bdark lymph node sign^ location of this lesion, as depicted by MRI, is not typical for facial filler 570 Insights Imaging (2017) 8:557–572 11. Ginat DT, Schatz CJ (2013) Imaging features of midface injectable patients justifies the use of expensive PET-CT. FDG PET-CT fillers and associated complications. AJNR Am J Neuroradiol is very sensitive but lacks the specificity to differentiate asep- 34(8):1488–1495 tic inflammation from septic infection [55, 81, 82]. 12. Park TH, Seo SW, Kim JK, Chang CH (2012) Clinical experience with polymethylmethacrylate microsphere filler complications. Aesthet Plast Surg 36(2):421–426 13. 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Injectable facial fillers: imaging features, complications, and diagnostic pitfalls at MRI and PET CT

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Springer Journals
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Copyright © 2017 by The Author(s)
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Medicine & Public Health; Imaging / Radiology; Diagnostic Radiology; Interventional Radiology; Neuroradiology; Ultrasound; Internal Medicine
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10.1007/s13244-017-0575-0
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Abstract

Insights Imaging (2017) 8:557–572 DOI 10.1007/s13244-017-0575-0 REVIEW Injectable facial fillers: imaging features, complications, and diagnostic pitfalls at MRI and PET CT 1 1,2 1 3 Pravin Mundada & Romain Kohler & Sana Boudabbous & Laurence Toutous Trellu & 1 1 Alexandra Platon & Minerva Becker Received: 30 June 2017 /Revised: 2 September 2017 /Accepted: 5 September 2017 /Published online: 4 October 2017 The Author(s) 2017. This article is an open access publication Abstract Silicone has signature MRI features, calcium hydroxyapatite Injectable fillers are widely used for facial rejuvenation, correc- has characteristic calcifications, whereas other injectable fillers tion of disabling volumetric fat loss in HIV-associated facial have overlapping imaging features. Most fillers (hyaluronic ac- lipoatrophy, Romberg disease, and post-traumatic facial id, collagen, and polyalkylimide–polyacrylamide hydrogels) disfiguring. The purpose of this article is to acquaint the reader have signal intensity patterns compatible with high water con- with the anatomy of facial fat compartments, as well as with the tent. On PET-CT, most fillers show physiologic high FDG up- properties and key imaging features of commonly used facial take, which should not be confounded with pathology. Abscess, fillers, filler-related complications, interpretation pitfalls, and cellulitis,non-inflammatory nodules,and foreignbody granulo- dermatologic conditions mimicking filler-related complica- mas are the most common filler-related complications, and im- tions. The distribution of facial fillers is characteristic and de- aging can help in the differential diagnosis. Diffusion weighted pends on the anatomy of the superficial fat compartments. imaging helps in detecting a malignant lesion masked by injected facial fillers. Awareness of imaging features of facial fillers and their complications helps to avoid misinterpretation of MRI, and PET-CTscans and facilitates therapeutic decisions * Minerva Becker in unclear clinical cases. Minerva.Becker@hcuge.ch Key points Pravin Mundada � Facial fillers are common incidental findings on MRI and Pravin.Mundada@hcuge.ch PET-CT scans. Romain Kohler � They have a characteristic appearance and typical anatomic romain.kohler@hopitalvs.ch distribution Sana Boudabbous � Although considered as safe, facial filler injections are as- Sana.Boudabbous@hcuge.ch sociated with several complications Laurence Toutous Trellu � As they may mask malignancy, knowledge of typical imaging Laurence.Trellu@hcuge.ch features is mandatory. Alexandra Platon � MRI is a problem-solving tool for unclear cases. Alexandra.Platon@hcuge.ch . . Keywords Injectable facial fillers Hyaluronic acid Division of Radiology, Department of Imaging and Medical . . . Silicone MRI PET-CT Granuloma Informatics, Geneva University Hospital, University of Geneva, Rue Gabrielle Perret Gentil 4, 1211 Geneva 14, Switzerland Present address: Division of Diagnostic and Interventional Abbreviations Radiology, Sion Hospital, Avenue du Grand-Champsec 80, CHA calcium hydroxyapatite 1951 Sion, Switzerland 3 CT computed tomography Division of Dermatology and Venerology, Department of Medical EC European Community Specialties, Geneva University Hospital, University of Geneva, Rue Gabrielle Perret Gentil 4, 1211 Geneva 14, Switzerland FBG foreign body granulomas 558 Insights Imaging (2017) 8:557–572 FDA Food and Drug Administration injection procedures and their complications to avoid misdi- FDG F - fluorodeoxy glucose agnosis and unnecessary biopsy. HA hyaluronic acid Tothebestofourknowledge,onlyveryfewarticleshavesofar HIV-LA HIV-associated facial lipoatropy dealt with the imaging features of injectable facial fillers [3, MRI magnetic resonance imaging 6–11]. The purpose of this article is to acquaint the reader with NIN non inflammatory nodule the anatomy of facial fat compartments, as well as with the prop- PAAG polyalkylimide - polyacrylamide hydrogels ertiesandimagingfeaturesofcommonlyused facialfillers,filler- PLLA poly-L-lactic acid related complications, interpretation pitfalls, and dermatologic PMMA polymethylmethacrylate conditions mimicking filler-related complications. PET-CT positron emission tomography CT SMAS superficial musculoaponeurotic system Imaging techniques Introduction Most often injectable facial fillers are detected incidentally on cross-sectional imaging studies. Therefore, radiologists need to be familiar with the imaging features of injectable fillers in "We are all of us stars, and we deserve to twinkle". order not to confound these with true pathology or vice-versa Marilyn Monroe in order not to miss true pathology obscured by filler injections. The number of people undergoing facial filler injections Patients with suspected filler-related complications are to get a youthful twinkle has strikingly increased in the last most often evaluated clinically and treated accordingly [12]. decade. In 2015, more than two million individuals in the Therefore, the reported use of cross-sectional imaging in this USA alone underwent hyaluronic acid (HA) injections of clinical setting is limited. Nevertheless, dermatologic condi- which the majority was for facial rejuvenation [1]. tions (cutaneous lymphoma, sarcoidosis, dermatomyositis) Although middle-aged women still constitute the majority, may present clinically with non-specific features and imaging it is not uncommon to see young adults and older people can help in differentiating these entities from filler-related undergo facial filler injections [2]. These injections, touted complications. The imaging requirements for the evaluation as safe and simple Blunch-time procedures,^ have become of the facial skin and subcutaneous tissues including facial an attractive alternative to incision-needing cosmetic surgery fillers vary according to the practicing centre. Depending on such as facelift procedures. Apart from the desire to look the availability, radiologists use MRI or high-frequency ultra- young, other indications include the correction of disabling sound to assess the location and volume of the injected facial volumetric soft tissue loss in HIV-associated facial fillers and to evaluate filler-related complications. At our in- lipoatrophy (HIV-LA), Romberg disease, and post-surgical stitute, MRI is the preferred modality due to its excellent soft and post-traumatic facial disfiguring [3–5]. tissue discrimination capability, large field of view, and ability The injection of dermal fillers gives desirable cosmetic to provide anatomic, quantitative, and functional information. outcome by erasing skin rhytides or restoring facial volume MRI has an excellent ability to detect soft tissue inflammation, loss, or both. The commonly injected sites on the face include abscess, and also foreign material in the soft tissues [13]. It is the perioral area, periocular region, nasolabial folds, malar fat preferred over ultrasound for the localisation of dislodged pad, marionette lines, glabella, and lips. The rising demand for fillers because it provides anatomical reference [2]. aesthetic procedures has led to the introduction of multiple At our institution, the MR examination protocol for facial injectable dermal fillers on the market. The actions by which fillers and dermatologic conditions includes high-resolution these fillers produce the desired cosmetic outcome differ from thin-slice (512 × 512 matrix for a field of view of 16-20 cm, each other and, thus, their complications and imaging features. 1-3 mm slices) acquisitions on a 1.5 or 3 Tesla MRI magnet A radiologist may be asked to evaluate the complications, with surface coils and parallel imaging techniques. We acquire extent, and location of a known facial filler injection. The the following sequences: T1 W (axial), T2 W ± fat saturation incidentally detected facial filler poses a diagnostic challenge or a STIR sequence (axial and coronal), diffusion weighted because the patient may forget, deny the history of filler injec- sequences with ADC maps (axial), and post gadolinium injec- tion, or may not know what type of filler was used [6]. It is a tion T1 W with fat saturation. If the injected filler is not reality of the world market of facial rejuvenation that facial known, a Bsilicone only^ sequence with simultaneous water filler injections are not only performed by qualified physi- and fat saturation (axial) before gadolinium injection should cians, but also by many unlicensed practitioners. It is impera- equally be obtained. A Bsilicone-only^ sequence is designed tive for the radiologist to remain abreast with the commonly to suppress all tissues except silicone. It is a combination of inversion recovery–turbospinecho(IR-TSE)withaTI used injectable facial fillers, the anatomical context of Insights Imaging (2017) 8:557–572 559 chosen to suppress fat signal (TI = 230 ms) and a spectrally superficial and deep fat layers separated by the superficial selective pre-pulse, which suppresses water [14]. Although musculoaponeurotic system (SMAS). The SMAS is a three- widely used to image patients with silicone breast implants, dimensional fibrous network that connects the periosteum, the the sequence is rarely obtained in other parts of the body. For muscles of facial expression, the platysma, and the fascia of the detection of injected silicone in the face, the sequence the parotid gland with the dermis [20]. The superficial fat layer parameters at 3 T MRI that are used in our institution are as (located superficial to the SMAS) was long considered a sin- follows: TR = 7.8 ms, TE = 3.69 ms, TI = 230 ms, flip gle confluent mass, and treatments were designed to lift and angle = 20 deg., voxel size = 1.5 × 1.5 × 6.0 mm, one average, reposition the fat pad as one single unit [21]. Similarly, prac- six concatenations. We equally recommend inclusion of a titioners injected facial fillers in arbitrarily defined facial com- DWI sequence in the protocol for two reasons. First, DWI partments [21]. More recently, Gosai et al. were the first to helps in detecting a malignant lesion masked by injected facial classify the superficial facial fat into medial and lateral com- fillers [15]. Second, DWI discriminates between a frank ab- partments (units) based on their relationship with the underly- scess and inflammation and, thus, helps in avoiding futile ing muscles of facial expression on MRI [22]. Rohrich and attempts of percutaneous aspiration [13]. Pessa demonstrated the actual anatomical divisions of the fa- High-frequency ultrasound is a safe, cost-effective, and wide- cial fat by injecting methylene blue dye into cadaveric facial ly available modality for the evaluation of facial fillers. Various specimen [23]. Subsequent studies by Rohrich et al. and other studies have documented its ability to localise commonly used groups validated the anatomical division of the facial fat and facial fillers. Ultrasound has also been useful to detect filler- also identified additional distinct compartments [24–28]. In related complications, such as abscessesorgranulomaslocalised 2012, Girrloff et al. quantified various facial fat compartments in the superficial fat spaces. In cases with suspected deep spread on CT scans after injecting iodinated contrast in a cadaveric of infection, MRI or contrast-enhanced CT (in the emergency facial specimen [29]. setting) is, however, necessary. Operator dependability and poor The superficial fat compartments (between the dermis and reproducibility remain major shortcomings of ultrasound in the the SMAS) and the deep fat compartments (between the evaluation of facial fillers [16–19]. SMAS and the periosteum of the facial bones) are illustrated CT does not offer advantages over MRI. However, it can in Figs. 2 and 3. These fat compartments are separated from identify calcifications, which are a hallmark of certain fillers each other by fibrous membranes, which carry perforator ves- and filler-related complications (see below). To reduce the sels. Schaverien et al. suggested that the highly organised radiation exposure, cone beam CT (CBCT) can be used as anatomical arrangement of the facial fat and the associated an alternative to CT to identify calcifications. However, vasculature are probably related to the embryologic develop- CBCT does not allow assessment of soft tissues. Therefore, ment of the facial musculature [30]. contrast-enhanced CT is preferred whenever infectious com- Facial fat in these compartments age differently plications are suspected. (hypotrophic versus hypertrophic changes or ptosis). For ex- F18- fluorodeoxyglucose (FDG) positron emission ample, ageing causes hypertrophic ptotic changes in the tomography-CT (PET-CT) has been found useful for the de- nasolabial fat and middle cheek fat, and hypotrophic involu- tection of the source of infection/ inflammation in the body tion in the lateral temporal cheek fat and deep medial cheek ahead of morphological changes. FDG PET-CT is increasing- fat, respectively. In patients with HIV-LA, substantial volu- ly used in the evaluation of fever of unknown origin, large metric changes of the superficial fat compartments vessel vasculitis, complicated sarcoidosis, osteomyelitis, HIV- (nasolabial, medial and middle superficial cheek fat) occur, related infections, and infections in the immunocompromised. whereas deep facial fat units appear to be less affected [31]. However, the use of FDG PET-CT is not recommended for the Therefore, qualitative assessment of these compartments plays evaluation of injectable facial fillers as increased FDG uptake an important role in facial rejuvenation methods and, in par- is non-specific and can be seen both in patients with and ticular, in deciding which fat compartments should be without complications caused by injectable fillers [11]. The volumised [32, 33]. Knowledge of facial fat compartments increased FDG uptake associated with injectable fillers is a may also help in understanding facial filler distribution and typical pitfall (Fig. 1), which may mimic a malignant tumour migration. or an infectious process depending on the clinical situation. Because of its high soft tissue resolution, MRI is excellent- ly suited to depict the facial fat units. Their relative position with respect to the SMAS, orbit and facial skeleton allows Imaging-relevant anatomy of facial fat correct identification of individual compartments (Fig. 3). compartments Nevertheless, the tiny fibrous septae that separate these com- partments, as well as the supporting ligaments of the face Traditionally, surgeons performing facial rejuvenation injec- cannot be seen on routine high-resolution MR images obtain- ed with standard coils. tions and cosmetic surgeries divided the facial fat into the 560 Insights Imaging (2017) 8:557–572 Fig. 1 45-year-old female patient evaluated with PET-CT for lymphoma on CT (arrows in b) and hardly enhancing on post-gadolinium T1 W fat staging. Coronal PET-CT image (a) reveals incidentally detected FDG saturated sequences (c, arrows). The patient had a history of silicone avid areas in bilateral nasolabial fat compartments (arrows). injections four years earlier. She had no filler-related symptoms SUVmean = 4.6, SUVmax = 5.9. The areas appear mildly hyperdense Types of facial fillers and normal imaging features (<24 months), and permanent. Rapidly resorbable fillers include HA, collagen and autologous fat. Slowly resorbable fillers in- The Food and Drug Administration (FDA) of the USA considers clude PLLA, CHA and dextran, whereas permanent fillers in- injectable facial fillers as medical devices used to improve ap- cludeliquidsiliconeandPMMA[36].Siliconeisthemostwidely pearance and without health benefit [34]. The classifications of used non-resorbable synthetic substance for medical purposes. injectable facial fillers vary according to their properties such as Of the three forms of silicone, only the liquid silicone is used as natureofthefiller,timeintervalforitsbiodegradation,andwheth- facialfillerwhiletheelastomerandgelareusedinbreastimplants er it is composed of one or more materials [35, 36]. The filler can [37, 38]. The FDA and the European Community (EC) do not beautologous,biological,orsynthetic.Autologousfillersconsist recommend all commercially available products. While some of the patient’s own body fat. Biological fillers consist of either products may be FDA approved, they are not EC approved and collagen of bovine, porcine, or human origin or hyaluronic acid vice-versa [39, 40]. Besides, some products have a limited ap- (HA) of bacterial origin. Synthetic fillers include paraffin, sili- proval, which limits their use to the specified areas in the face. cone, calcium hydroxyapatite (CHA), polymethylmethacrylate (PMMA) microspheres, polyacrylamide hydrogel, Autologous fat fillers hydroxyethyl/ethyl methacrylate, and poly-L-lactic acid (PLLA) [36]. Based on biodegradation features, fillers can be Autologous fat was one of the earliest used injectable fillers to classified as rapidly resorbable (<12 months), slowly resorbable reconstruct facial scars [41]. Its use has declined over the years Fig. 2 Schematic illustration of the subcutaneous facial fat cheek fat (4), the central forehead fat (5) and paramedian forehead (6) compartments. 3D reconstruction from contrast enhanced CT. Position fat, the superior orbital (7), inferior orbital (8) and lateral orbital (9) fat, of the retaining ligaments of the face (white lines), superficial (yellow), and the superior jowl (10) and inferior jowl (11) fat. b The deep group and deep (light green) fat compartments in relationship to the facial (light green) includes the following compartments: the medial (12) and skeleton. a The superficial group (yellow) includes the following lateral (13) sub-orbicularis oculi fat, the deep medial cheek fat (14), the compartments (units): the nasolabial fat (1), the medial superficial buccal fat pad (15) and Ristov’s space (16). Modified after Rohrich et al. cheek fat (2), the middle superficial cheek fat (3), the lateral temporal and Alghoul et al. [23, 83] Insights Imaging (2017) 8:557–572 561 inferior jowl fat (11), medial sub-orbicularis oculi fat (12), deep medial Fig. 3 Facial fat compartments as depicted by routine MRI. a – d. Axial T2 W slices. e. Sagittal T2 W image through the mid-pupillar line. f – g. cheek fat (14), buccal fat pad (15). Muscles and other relevant structures: Coronal T2 W slices. For easier correlation with the schematic drawing depressor anguli oris muscle (DAOM), frontalis muscle (FM), levator shown in fig. 1, the same numbers were used for the superficial and deep labii superioris and levator labii superioris aleque nasi muscles (LLSM), facial fat compartments. Fat compartments: nasolabial fat (1), medial platysma muscle (PM), orbicularis oculi muscle (OOCM), orbicularis oris superficial cheek fat (2), middle superficial cheek fat (3), lateral muscle (OOM), superficial musculoaponeurotic system (SMAS), temporal cheek fat (4), paramedian forehead fat (6), superior orbital fat Stensen’s duct (SD), zygomaticus minor and major muscles (ZM) (7), inferior orbital fat (8), lateral orbital fat (9), superior jowl fat (10), due to inconsistent resorption rates, which vary from months often has a streaky appearance [6]. The imaging appearance of to years. However, autologous fat is regaining popularity in collagen may change if mixed with other substances to pro- some parts of the world due to improved harvesting tech- long its cosmetic effect. niques [41–43]. On CT, the filler appears as low attenuation soft tissue. On MRI, it follows fat signal on all sequences and Calcium hydroxyapatite (CHA) fillers may show a thin pseudocapsule (Fig. 4). CHA (Radiesse) comprises spherical microparticles of bone- Collagen fillers like composition suspended in an aqueous sodium carboxymethyl cellulose gel. Marionette lines and nasolabial Collagen is a major structural component of healthy skin. folds have been successfully corrected with CHA. The filler Bovine collagen was the first FDA-approved injectable der- has a tendency to nodule formation and foreign-body reaction, mal filler in the USA. The subsequently developed human which discourages its use for lip augmentation. The micropar- bio-engineered and porcine collagens gained popularity due ticles disintegrate over time, and the volumising effect may to low risk of hypersensitivity reactions as compared to their last for 1 to 2 years [9, 45]. However, the persisting soft tissue bovine predecessor. Collagen fillers may last from 6 to volume gain even after complete filler resorption implies 12 months, whereas collagen mixed PMMA microspheres in vivo de novo collagen formation [46, 47]. (Artefill) may last up to 5 years [6, 44]. On MRI, collagen CHA is hyperattenuating (HU 280-700) on CT and pre- appears hypointense on T1 W images and hyperintense on sents with well-defined linear streaks or rounded masses T2 W and STIR images (Fig. 5) due to its high water content (Fig. 5). CT filler density diminishes after 12 months as the [6, 8]. Collagen deposits may show minimal peripheral en- microspheres get absorbed, and eventually the filler may dis- hancement in the first 2 months of injection. This minimal appear after 24 months [9, 46]. On MRI, CHA fillers have low enhancement is not indicative of infection. On CT, collagen to intermediate signal intensity on T1 W and T2 W images. fillers show fluid attenuation and the injected subcutaneous fat They show mild post-contrast enhancement due to 562 Insights Imaging (2017) 8:557–572 Fig. 4 61-year-old woman with discrete facial asymmetry and induration Patient confirmed autologous fat filler injection nine months back. The of the left cheek. She had internal fixation of a left tetrapod facial fracture hypointense rim around the filler deposit on T2 and the post-gadolinium 25 years back. MRI showed a well-circumscribed lesion, isointense to fat rim enhancement on T1 represent a fibrous pseudo-capsule due to scar on T2 W (a) and post-gadolinium T1 W fat saturated (b) sequences (long tissue formation: dashed short arrow in (a) and short arrow in (b) arrows). The lesion is located in the left superficial medial cheek fat. vascularisation of the calcified matrix [9, 48]. On FDG PET- incidentally, warrants correlation with patient history and mor- CT, CHA appears strongly FDG-avid, which, if detected phological imaging to avoid misdiagnosis [9]. Fig. 5 Commonly injected facial fat compartments and characteristic labii superioris aleque nasii, and zygomaticus minor muscles). c 64-year- aspect of various fillers at MRI and CBCT. In all presented cases, the old man with HIV-LA and HA injection 6 months earlier. Axial STIR patients were symptom-free and were imaged for other reasons. a 55- image reveals HA injection performed in the deep medial compartment year-old woman with collagen filler injections 5 months previously. On (short arrows) and buccal fat pad (large arrow). d 45-year-old woman coronal STIR image, collagen filler injections in the superior (dashed with bilateral HA injections. On coronal STIR image, HA is detected in arrows) and inferior (arrows) jowl compartments are seen as hyperin- inferior orbital compartments (short arrows) and nasolabial fat compart- tense, lobulated and reticulated areas. Asterisks indicate large artefacts ments (long arrows). e and f 60-year-old woman with bilateral HA injec- due to dental implants. b 62-year-old woman with CHA injections 3 years tions for cosmetic purposes. On coronal STIR image (e), HA injection of previously. On axial CBCT with bone window settings, streaky calcific the superior (dashed arrow) and inferior jowl compartments (arrow). density of CHA filler is seen in the left and right medial and middle Sagittal T1 W image (f) shows hypointense HA in the nasolabial fat (short superficial cheek compartments (arrows) and extending towards the left arrow), medial superficial cheek compartment (dashed arrow) and jowl lateral temporal cheek fat (short arrow). Thin dashed arrows point at the compartment (arrow). Non-injected buccal fat compartment (asterisk) SMAS and muscles of facial expression (levator labii superioris, levator Insights Imaging (2017) 8:557–572 563 Hyaluronic acid (HA) fillers attenuation on CT [6, 10, 47]. On FDG PET CT, there is increased uptake due to the filler-induced subclinical inflam- HA is a naturally occurring polysaccharide in healthy soft mation [58]. tissue, which binds the collagen and elastic fibres to provide intercellular stability. The naturally occurring HA has a very Polyalkylimide and polyacrylamide hydrogels (PAAG) short half-life. Pre-processing and cross-linking prolong the half-life of HA before its use as filler [43, 49]. Depending PAAG (Bi o-Alcamid = polyalkylim ide and on cross-linking HA fillers can be divided into cohesive Aquamid = polyacrylamide) are non-biodegradable injectable (monophasic) or non-cohesive (biphasic) gels. The cohesive hydrogel polymers. Aquamid comprises 2.5-4.5% crosslinked gel disperses diffusely to fill the small gaps between collagen polyacrylamide hydrogel and 97.5-95.5% purified water [35, and elastin bundles, whereas the non-cohesive gel deposits in 59]. PAAG induces accumulation of fibroblasts and macro- puddles [44, 50]. The injected HA combines with natural HA phages, and formation of a fibrous capsule [35]. Correcting in the soft tissue, binds water due to its hygroscopic nature and nasolabial fold, facial contouring, rhytides, and facial also induces new collagen formation. Thus, a volume is cre- lipoatrophy by PAAG injection is approved in many coun- ated, which may last for a few months to 1 year [51–53]. HA tries. Delayed reactions like infection, granuloma and migra- fillers are the most widely used fillers for their safety, easy tion have been reported [60]. All abscesses reported in a study reversibility, and minimal side effects. occurred after polyalkylimide gel [2]. In analogy to other MRI with T2 W and contrast-enhanced T1 W sequences fillers containing large amounts of water, PAAG fillers appear can accurately assess the volumetric and temporal changes of hyperintense on T2 Wand hypointense on T1 W sequences [2, subdermal HA filler injection [3, 54]. Because of its high 61] and reveal no post-contrast enhancement. On CT, PAAG water content, HA filler appears strongly hyperintense on appears as a well-defined area of fluid attenuation. T2 W and STIR sequences and hypointense on T1 W se- quences. Injected HA typically shows well-defined serpigi- nous margins at imaging (Fig. 5). Minor post contrast en- Silicone oil filler hancement is seen in the initial 6 months of injection, which represents increased vascularisation of injected tissue. This Silicone is a permanent filler, which restores volume and in- minor enhancement and the signal intensity on T2 W images duces new collagen formation. The pure silicone oil is consid- gradually decrease during the first year after injection [3]. The ered inert, minimally antigenic, non-carcinogenic, and a poor volume gain after HA filler injection is maximal in the first medium for bacterial growth [62]. Its use as a tissue filler month and remains more or less stable for the next 12 months. became controversial due to the reported high rate of compli- Using 3D fat-saturated T2 W sequences, HA was found in cations. Many authors attribute the silicone injection-related anatomical regions situated much deeper than the compart- complications to the poor injection technique, use of industrial ment of the initial injection [3]. The hydrophilic nature of silicone and large volume injections [62, 63]. The off-label use HA and the diffusion permeability of the fibrous septae be- of FDA/CE approved silicone products as facial fillers with tween the facial fat compartments are thought to be responsi- microdroplet techniques is reported to have minimal side ef- ble for this finding [3]. As HA binds water in vivo and as the fects [62, 63]. Illicit silicone oil, however, continues to be in filler also induces in vivo procollagen formation (which has use as facial filler in many parts of the world despite high water content), MRI actually depicts a mixture of all complications. three substances (injected HA, bound water, and de novo The MRI appearance of silicon facial fillers varies accord- formed procollagen) and differentiation between these three ing to viscosity and purity. The low viscosity silicone oil is components is not possible with MRI [3]. On CT, HA fillers slightly hyperintense to water on T1 W images, iso- or slightly appear as areas of soft tissue attenuation. On PET-CT, they are hypointense to water on T2 W images, and hyperintense on occasionally FDG-avid [55]. the Bsilicone only^ sequence. High viscosity silicone oil is hypointense on T2 W images [6, 10]. A Bsilicone-only^ se- Poly-l-lactic acid (PLLA) quence is designed to suppress all tissues except silicone [14] (Fig. 6). On fat-saturated T1 W images silicone may appear PLLA (Sculptra), a biodegradable synthetic polymer hyperintense and show chemical shift artefact [64]. Post con- suspended in sodium carboxymethylcellulose and mannitol trast fat-saturated TIW images may show variable enhance- has been used for the treatment of HIV-LA and the correction ment depending on the inflammatory or reactive changes in of rhytides [56]. It induces subclinical inflammation with col- the surrounding tissues. On CT, silicone appears slightly lagen formation and fibrosis [57]. It has a gradual onset of hyperdense [6]. On ultrasound, it shows a hyperechoic action and results last for a few years [56]. PLLA appears Bsnowstorm^ appearance, which obscures soft tissue details hypointense on T2 W images and shows soft tissue [17–19]. 564 Insights Imaging (2017) 8:557–572 Fig. 6 Two different patients with filler injections performed under (arrows in b, e) suggesting an inflammatory reaction. However, in patient unclear circumstances (patient 1, 53-year-old woman, a-c; patient 2, 46- 1, the injected areas appear hypointense on the silicone only sequence year-old woman, d-f) developed diffuse swelling and induration of the (arrows in c), whereas in patient 2 the injected areas appear strongly lips and cheeks 1 year after the respective procedures. The injected filler hyperintense. Based on these images, the diagnosis of granuloma was a mixture of CHA and collagen in patient 1, and it was not known in formation due to CHA and collagen in patient 1 and due to silicone oil patient 2. In both patients, the filler and the resulting soft tissue changes in patient 2 was made. Biopsy obtained in both patients confirmed the show intermediate-to-low signal intensity on T2 W images (arrows in a, radiologic diagnosis, in particular biopsy also confirmed the presence of d), and nodular and strong enhancement on postgadolinium T1 W images silicone with a characteristic Swiss cheese pattern at histology Autologous fibroblasts and non-complicated facial fillers in 100% of patients [2, 8, 10].Accordingtothesestudies, MRI could detect injected Tissue harvested from the postauricular area is cultured to pro- fillers as small as 2 mm in diameter [10], and also those duce fibroblasts cell lines. These fibroblasts are injected intrader- filler-related abscesses and granulomas missed on clinical mally to correct dermal depressions and rhytides. Autologuous examination [2]. fibroblasts increase thickness and density of dermal collagen. Regarding filler characterisation, Tal et al. have claimed They have a low incidence of hypersensitivity [35, 44]. that they could accurately differentiate between the indi- vidual types of injected fillers on the basis of their signa- Paraffin ture MRI features [8]. The existing literature and experi- ence at our institution do not support their assertions. As Paraffin was perhaps the first substance to be used as facial discussed in the previous section, most facial fillers (HA, filler and caused severe granulomatous reactions and collagen, and PAAG) have a similar appearance on MRI Bparaffinoma formation^ [65]. CT features of Bparaffinoma^ due to their high water content [3, 6, 10]. In our experi- include calcific rounded foci and soft tissue density nodules ence, only silicone fillers have a characteristic MRI appear- with a calcific rim [7]. ance on the Bsilicone only^ sequence. The Bsilicone only^ sequence is, however, prone to artefacts from non- homogenous fat and water saturation, especially in the Role of imaging for filler detection presence of dental implants. Therefore, experience and and characterisation caution are required for its interpretation. CHA shows characteristic linear or clumps of calcifications The detection of injected facial fillers is straightforward on CT [46], whereas all other filler types do not show calcifi- with cross-sectional imaging provided radiologists are cations unless the injected filler causes foreign body reaction. aware of the typical injection sites (Figs. 1, 2, 3, 4, 5,and Foreign body granulomas (FBGs) induced by liquid silicone 6) and of MRI/CT features. Earlier published studies have or paraffin have typical eggshell, rounded, or nodular calcifi- demonstrated the ability of MRI in locating all complicated cations [7, 11]. Insights Imaging (2017) 8:557–572 565 Complications of facial filler injections and role Most complications like erythema, bruising and hypersen- of imaging sitivity do not require radiological evaluation. Non- erythematous nodules formed soon after injection are caused Notwithstanding the much-touted minimally invasive nature by the uneven distribution of the filler and are likely to resolve of facial filler injection procedures and safety claims of filler spontaneously. Even the nodules caused by inflammation/ manufacturers, all types of injectable facial fillers can cause infection may resolve spontaneously [66]. In one study in- short-term and long-term complications [38, 40, 66, 67]. volving PLLA injection in HIV-LA, patients showed small Short-term complications are usually related to the procedure palpable, painless nodules in 44% cases. Most of these nod- itself and early host response to the injected material. Early com- ules resolved spontaneously [74]. plications occur within days or weeks of the injection procedure and manifest clinically with erythema, bruising, hyperthermia, Abscess formation swelling, hypersensitivity, nodule formation, and lumpiness in the injection area. They are due to over-injection or mal- The filler injection interrupts the natural barrier of the skin and distributionof thefiller,ortheyare causedby iatrogenic infection increases the possibility of infection. Injections performed by [66, 68]. Infection is rare and has been reported in <0.2% of a untrained hands and use of illicit products increase the risk of series of 1300 patients treated with PAAG; more recent publica- abscess formation. Kadouch et al. reported a high incidence of tionssuggestanoverallinfectionrateof0.04%[69,70].Infection abscess formation with PAAG [2]. Nevertheless, an abscess is mainly caused by inadequate skin disinfection. Infections with can occur with all types of filler injections. Like an abscess Staphylococcus epidermidis, Propionibacterium acnes, and anywhere else in the body, filler-related abscess appears as a nontuberculous mycobacteria (NTM) usually manifest early or lobulated fluid collection with rim enhancement and adjacent within 3-6 weeks after inoculation. However, delayed manifes- fat stranding on MRI (Fig. 8). On DWI, the abscess may show tations(monthstoyearslater)arenotexceptional(Fig.7)[70].As restricted diffusion [13]. Nevertheless, infected filler deposits NTM are known to exist in tap water, infection occurs when tap and infected fluid collections may show absent restriction on water contaminates the injection procedure [71]. DWI (Fig. 8). To avoid this pitfall, correlation with symptoms Occasionally, severe and acute complications like local soft and morphologic MR images is essential. tissue necrosis, blindness, and cerebral infarct may occur due to vascular occlusion [72, 73]. A retrospective study reported Non-inflammatory nodule (NIN) and foreign body acute blindness with glabella and nasolabial fold injection of granuloma (FBG) autologous fat in seven patients, HA in four patients and col- lagen in one patient, respectively [72]. FBG and a NIN differ on imaging and histopathology [75]. Long-term complications are related to the injected filler Differentiation between the two conditions is important as it itself and delayed host response. These complications include influences patient management [10]. A FBG is a non-allergic FBG, delayed manifestations of infection including abscess chronic granulomatous reaction that appears months to years formation, migration of filler, disfiguring nodules and scarring, after filler injection and grows very slowly. FBG can be mul- tissue necrosis and ulcer, and persistent discoloration [40, 66]. tiple and recurring. On histology, FBG has wide spaces Fig. 7 A 49-year-old woman developed bilateral painful facial swellings medial deep cheek fat and buccal fat pads. These areas display reticulated and redness of skin 4 months after bilateral facial injection of PAAG enhancement on post contrast fat saturated T1 W images (arrows in c) fillers. On MRI, ill-defined streaky areas of signal abnormalities, suggesting cellulitis/infection. Haematological investigations showed hyperintense on axial STIR (arrows in a) and iso- to hypointense on raised inflammatory markers. Patient responded to treatment with axial T1 W images (arrows in b), were seen in bilateral superior jowl antibiotics and medial superficial cheek fat compartments with extension to bilateral 566 Insights Imaging (2017) 8:557–572 Fig. 8 A 65-year-old woman developed pain, erythema, and bilateral seen on CT have a high protein content (hypo-isointense on T2 and T1). cheek swelling after 6 months of HA facial filler injections. a Contrast- On b1000 (e) and ADC map (f), these rim-enhancing lesions show enhanced CT shows bilateral Bgrape-like^ hypodense, rim-enhancing variable diffusivity (long arrows). ADC values were between 1.2 and −3 2 areas (long arrows) and solid appearing enhancing nodules (short 2× 10 mm /s. The solid lesions (short arrows)showstrong arrows) in the nasolabial fat, medial and middle superficial cheek fat enhancement on MRI and no restricted diffusivity. Surgery confirmed compartments. T2 W (b), T1 W (c), and fat-saturated gadolinium bilateral infected fluid collections and isolated FBG enhanced T1 W (d) images reveal that the rim-enhancing areas already between the foreign body particles, abundant macrophages, histopathology, and fillers with or without thin rim enhancement fibroblasts and giant cells. It shows finger-like projections in were non-inflammatory on histopathology. Kadouch et al. did not adjacent tissues. Although all types of injectable fillers cause dwellondifferentiatingFBGfromnon-granulomatousinflamma- FBG formation, FBG is most often seen after long-standing tory changes. In our experience, FBGs show enhancement on silicone oil injection (Bsiliconoma^, especiallywithnonmed- MRI; however, the degree of enhancement may vary (Figs. 6, 8, ical grade silicone), whereas fillers such as HA have a low 9,and 10). As suggested by Giorlamo et al., nodular or diffuse FBG incidence. FBG shows three histological types: cystic, enhancement typically suggests FBG, whereas streaky enhance- lipomatous, and sclerotic. Discussion on the histological FBG ment in the subcutaneous fat corresponds to cellulitis (Fig. 9). On types is, however, beyond the scope of this article [39, 40, 76]. CT, FBGs may show punctate or eggshell classifications [6, 39, NINsare singlelumpsthatusuallyappear1to2monthsaftera 40] and on PET-CT, FBGs show high FDG uptake (Fig. 10). technically erroneous superficial facial filler injection. They oc- According to Kadouch et al. [2], clinico-radiologic agree- cur more often after injections of non-resorbable than resorbable ment was substantial for fillers without complications and fillers. In patients with HIV-LA, NINs can be seen years after non-inflammatory nodules (85%), moderate for abscesses PLLA injection. NINs are usually evenly sized, appear harder (60%), fair for low-grade inflammation (32%), and slight for and whiter than granulomas, and remain stable. On histology, migration (9%). The patient population in the study of they show a dense cluster of foreign material, few macrophages, Kadouch et al. comprised patients with filler injections either occasional giant cells, and a fibrous pseudo-capsule [39, 40, 76]. for cosmetic reasons or treatment of HIV-LA [2]. In our prac- The MRI features of FBG (Figs. 6, 8, 9,and 10) are described tice, regular use of MRI makes decision-altering contributions differently in the literature [77, 78]. Girolamo et al. have demon- to the evaluation of filler-related complications and in patients strated 100% correlation between the post-contrast enhancement with both head-neck cancer and fillers. Thus, the utility of around the complicated filler and histological evidence of granu- MRI for the assessment of filler-related complications might loma formation, whereas non-granulomatous inflammation did differ in a different set of patients and, also, according to the not show enhancement [10]. Contrary to this, Tal et al. observed clinical expertise. Nevertheless, the high cost of MRI warrants that histologically proven granulomas (n = 4) did not show post- its judicious use [10, 79]. contrast enhancement on MRI [8]. According to Kadouch et al., According to the literature, FBG is usually treated with complicated fillers with rim enhancement and adjacent fat intralesional corticosteroid injection, systemic steroid therapy stranding (n = 11) corresponded to inflammatory nodules on and, occasionally, surgical excision. NIN requires surgical Insights Imaging (2017) 8:557–572 567 Fig. 9 A 57-year-old woman with a remote history of collagen filler (short black arrow in b) and left SMAS (arrowhead) appear iso- injections developed facial lumps. Histologically proven FBGs (dashed hypointense on T1 W and hypointense on STIR images. On coronal arrows) in the right and left jowl fat units have high signal intensity on post gadolinium fat saturated T1 W image, the degree of enhancement STIR (a), low signal intensity on T1 W image (b), and strong of FBG (dashed arrows in c) and of fibrosis around FBG (short arrows in enhancement on fat saturated T1 W (c). The fibrosis around the c) appear similar and cannot be differentiated for each other on the basis granuloma (short white arrows in a, b) and the thickened right SMAS of enhancement alone excision and does not respond to intralesional or systemic migrate through lymphatic or haematogenous routes and may steroid therapy. mimic a malignant pathology of distant organs or granuloma- tous skin conditions [62, 66, 80]. Authors have showed that MRI was able to detect migrated facial fillers even in the Migration of fillers and overfilling absence of clinical suspicion and denial of a history of filler injection [2, 11]. Filler migration is a common indication for evaluation with MRI. Poor injection technique has been thought to cause filler Overfilling due to excessive filler injection can cause serious patient dissatisfaction. The incidence of overfilling migration. Although migration is not typical of any particular filler, permanent fillers (typically silicone) are more likely to varies from 0.8 to 8% of cases. It may appear as a focal lump or diffuse facial asymmetry. Overfilling due to HA migrate due to their longer presence in the body. They may Fig. 10 66-year-old woman with PET CT for fever of unknown origin. Palpable indurations of the nasolabial folds. FDG avid areas in bilateral nasolabial folds (arrows in a)appear of intermediate signal intensity on T2 W (b), isointense on T1 W (c), and homogenously enhancing on post-gadolinium T1 W fat satu- rated (d)sequences (arrows). The location of this signal abnormality prompts the diagnosis of previ- ously injected facial filler. Histopathology showed FBG due to probably PLLA facial filler injections 568 Insights Imaging (2017) 8:557–572 Fig. 11 75-year-old woman with unknown facial filler injections eight saturated contrast enhanced T1 W image (dashed arrows in c). It shows months back and left epiphora since one month. Coronal STIR (a)and restricted diffusion on the corresponding ADC map (arrow in d). coronal gadolinium enhanced fat saturated T1 W (b)images show the Furthermore, one would not expect filler injection in this location. sites of previous filler injections (short arrows) and an irregular mass in Initial histopathology showed evidence of an inflammatory nodule. the left lacrimal fossa with extension to nasolacrimal duct (dashed arrows Repeat biopsy, however, revealed squamous cell carcinoma of the in a and b). The spiculated, enhancing lesion well seen on the axial fat lacrimal sac injection can be reversed to some extent by injection of complicated silicone implants may or may not show silicone hyaluronidase. Needle aspiration and surgical excision contents on imaging [2, 6, 8]. mayalso be required[11]. Pitfalls in image interpretations Scarring and lymph node enlargement Facial fillers may pose a diagnostic dilemma for several rea- Severe chronic inflammatory thickening of the soft tissues sons. The patient may forget or deny the history of facial filler may cause significant disfiguring and subsequent scarring. injection due to social taboo. Injection performed by an unli- These reactions are common with permanent fillers, especially censed practitioner may be denied for medical insurance pur- silicone. CT/MRI may show a thick band-like subcutaneous pose. The patient may not know or remember the type of the deposition of silicone associated with diffuse soft tissue swell- injected filler. Incidentally detected or complicated facial filler ing and post-contrast enhancement (figure 6)[6, 62, 66]. Mild may mimic recurrent cancer on MRI in patients with previous enlargement of lymph nodes associated with facial fillers is head and neck cancer. Furthermore, facial filler injection may non-specific. The enlarged lymph nodes in case of mask a neoplasm (Fig. 11). Insights Imaging (2017) 8:557–572 569 Lack or denial of history may confuse filler-related com- cells, mainly macrophages [81]. The increased FDG uptake by plications with dermatological conditions including sarcoido- facial fillers may pose a diagnostic challenge in head and neck sis, dermatomyositis, and cutaneous lymphoma. On imaging, cancer and melanoma patients by mimicking a new primary or these dermatological conditions appear mildly hypointense on recurrence, especially if the injection is performed between T2 W images, may show restricted diffusion, and the involved two follow up scans and the history is denied or simply for- facial soft tissue compartments are atypical for filler injection gotten. Careful correlation with morphological imaging and (Fig. 12). An atypical anatomical location for facial filler in- the anatomical context of FDG uptake may help in avoiding jection or migration and restricted diffusion on DWI warrants unnecessary biopsy. histopathological correlation to exclude malignancy and other Although FDG CT/MRI is not an imaging modality of dermatological conditions. choice for the detection of filler-related complications, it is Uncomplicated facial fillers, FBG, non-granulomatous in- increasingly used for the detection of a source of infection flammation and abscess associated with facial fillers may and inflammation, sarcoidosis, and large vessel vasculitis. show increased uptake on FDG PET-CT/MRI. This uptake The increased cost of treating multi-drug resistant infections is attributed to increased glycolysis in activated inflammatory in immune-compromised patients, diabetics, and elderly Fig. 12 49-year-old woman presentingwithslowly progressing injection. Based on MRI features, the presumptive diagnosis of subcutaneous induration over the right cheek and with extension to the sarcoidosis, dermatomyositis, or cutaneous lymphoma was made and skin over the nose. Clinically, a facial filler injection related complication biopsy was recommended. Histopathology revealed sarcoidosis. was suspected as an underlying pathology. On MRI, the infiltrative lesion Subsequent CT of the chest (not shown) showed typical interstitial appeared hypointense on T2 W (arrows in a) and on T1 W images nodules and mediastinal lymphadenopathy. Retrospective analysis of (arrows in b) and showed avid enhancement on post contrast T1 W fat the head and neck MRI revealed no nodal involvement, in particular no saturated images (arrows in c, d). The lesion involves the superficial and Bdark lymph node sign^ [84]. Nevertheless, the nonenhancing dark deep layers of the facial fat and the SMAS. Note scattered rounded regions in c) corresponded histologically to sarcoid granulomas, the nonenhancing dark regions (dashed arrows) embedded in the strongly imaging features being strikingly similar to granulomas in nodes with enhancing cutaneous lesion in c) possibly suggesting granulomas. The the Bdark lymph node sign^ location of this lesion, as depicted by MRI, is not typical for facial filler 570 Insights Imaging (2017) 8:557–572 11. Ginat DT, Schatz CJ (2013) Imaging features of midface injectable patients justifies the use of expensive PET-CT. FDG PET-CT fillers and associated complications. AJNR Am J Neuroradiol is very sensitive but lacks the specificity to differentiate asep- 34(8):1488–1495 tic inflammation from septic infection [55, 81, 82]. 12. Park TH, Seo SW, Kim JK, Chang CH (2012) Clinical experience with polymethylmethacrylate microsphere filler complications. Aesthet Plast Surg 36(2):421–426 13. 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Published: Oct 4, 2017

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