Real-time MRI-guided percutaneous sclerotherapy treatment of venous low-flow malformations in the head and neck

Abstract

Purpose

This manuscript describes the technique of real-time MRI-guided sclerotherapy for low-flow venous malformations in the head and neck based on our institutional experience.

Materials and methods

Ethanolamine oleate is used as the sclerosant and is mixed with gadolinium for visualization during the procedure. The five procedural steps include: (I) an initial tri-plane T2-weighted sequence to visualize the lesion; (II) a T1 FSE or trueFISP sequence to assess needle placement and advancement within the lesion; (III) a tri-plane T1 FLASH sequence to monitor sclerosant injection; (IV) a T1 FSE or VIBE sequence to assess sclerosant coverage of the malformation before needle removal; (V) a post-procedural tri-plane T1 fat-saturated sequence to confirm sclerosant coverage of the lesion. Periprocedural medications typically include steroids, antibiotic prophylaxis, and non-steroidal anti-inflammatory medication. Patients are typically admitted for overnight observation.

Conclusion

Real-time MRI-guided sclerotherapy for low-flow venous malformations in the head and neck is effective and safe.

Keywords

Venous malformation real-time MRI guidance percutaneous sclerotherapy Ethanolamine Oleate

Introduction

Vascular low-flow malformations are vascular lesions of congenital origin, mostly involving soft tissue, which can be found in adults and children .¹ The general classification scheme of low-flow vascular malformations is based on the predominant epithelial cell type – capillary, venous, lymphatic, or mixed. Low-flow venous malformations (VM) are the most common vascular malformations comprising up to 64% of all vascular malformations.² Approximately 40% of VM appear in the head and neck region.^2,3 These vascular lesions occur sporadically in the majority of cases, and appear on physical exam as blue to purple cutaneous lesions that alter in size based on hormonal changes, compression, and valsalva maneuver.^4–6 Resulting symptoms of head and neck VM depend on location and potential thrombosis of the malformation; these symptoms can include pain, swelling, bleeding, muscular fibrosis, as well as local compressive effects on muscle, bone, orbit, parotid gland, larynx, and cranial nerves.^4,5,7 Cosmetic defects can be another manifestation of VM necessitating treatment.⁸

Image-guided sclerotherapy is an established therapeutic approach for VM. The overall aim of sclerotherapy is to induce death and atrophy of the malformation as well as to decrease recurrence rates by introducing a sclerosant agent into the vasculature of the lesion, thereby promoting inflammation, which results in acute thrombosis and subsequent fibrosis.^9–11 This reaction causes a decrease in the size of the VM lesion to relieve its associated symptoms and minimize risk of recurrence. This procedure has been traditionally performed using a multi imaging modality approach with magnetic resonance angiography, ultrasound, and CT guidance.^12–16 However, particularly in the complex anatomy of the head and neck region, CT has its inherent limitations and MRI is an attractive alternative due to its superior soft tissue contrast and decreased amount of dental implant artifacts.¹⁷ In addition MRI, unlike CT, is not associated with radiation exposure. Ultrasound can be useful in selective cases to identify VM based on the presence of cystic spaces and vasculature, particularly if the vasculature is thrombosed or filled with phleboliths.⁵ However, ultrasound has limited use for VM located adjacent to bony or fibrotic tissue in the head and neck, and its assessment of VM flow can be restricted if the flow is too slow to be detected by Doppler.^5,18,19 Compared to ultrasound, MRI offers superior visualization of VM local extension, including large draining veins and systemic communications, due to the increased signal contrast between the hyperintense VM lesion and hypointense surrounding structures on T2-weighted imaging.^19,20

Since the advent of MR fast gradient echo sequences, the temporal resolution of real-time MRI has been improved. As a result, real-time MRI has shown potential as an attractive and evolving single modality approach to perform image-guided sclerotherapy. MR can be used to accurately guide needle placement and assess sclerosant delivery.^9,10 Our institution has extensive experience with MRI-guided sclerotherapy, with well over 100 cases of treated vascular malformation in the last 11 years. In this technical development paper, we will elaborate on the technique of real-time MRI-guided sclerotherapy for VM in the head and neck region in a stepwise approach based on illustrative patient cases from our institution.

Technique

Pre-procedural therapy planning

For pre-procedural planning of VM treatment in the head and neck area, the modality of choice is contrast enhanced MRI (Figures 1 and 3). For assessment of morphology, T2-weighted sequences play a key role since the extent of the hyperintense vascular lesion can be well evaluated. For analysis of the microvasculature associated with the target VM, we use the time-resolved angiography with stochastic trajectories (TWIST), particularly to identify the presence of feeding arteries or large draining veins. If feeding arteries are identified, a pre-procedural angiogram must be performed to map the vasculature and potentially embolize arterial feeders before considering sclerotherapy. Large draining veins are considered a potential relative contraindication to sclerotherapy due to increased risk of non-target distribution of the sclerosant via the draining veins into the systemic venous circulation. In the case of VM with large draining veins – jugular or femoral access may be obtained for selective access and embolization or temporary occlusion of the target draining veins. The complete embolization or occlusion of these veins must be confirmed with angiography before real-time MRI-guided sclerotherapy can be conducted on the VM. All patients are evaluated in our outpatient vascular anomaly clinic, which is a multidisciplinary clinic involving interventional radiology, plastic surgery, dermatology, pediatrics, cardiology and occasionally other specialties including ENT and orthopedics.

Figure 1.

Pre-procedural work-up for 47-year-old female with temporal muscle VM. Panel (a): Coronal T₂w pre-contrast image showed prominent hyperintense lesion occupying the location of the right temporal muscle. This is consistent with complex intramuscular venous malformation. Based on the image, thinning of the underlining cortical bone was suspected. Panel (b): Remodeling of the right temporal bone is demonstrated based on the 3D volume-rendering image derived from CT dataset. Panel (c): The finding in panel (b) is also exhibited by the coronal CT image, confirming remodeling of the underlying right temporal bone. Panel (d): Venous phase time resolved MRA demonstrated temporal muscle vascular lesion enhancement with its deeper components. Another enhancing lesion, which was not clearly delineated on prior imaging, was seen in the anterior right maxilla region. These findings are consistent with extensive right-sided VM.

Figure 2.

This is the same patient from Figure 1 – a 47-year-old female with MRI-guided intervention of temporal muscle VM. Panels (a) and (b): Lesion location using a saline syringe prior to needle advancement based on axial and coronal trueFISP images .The trueFISP sequence should be performed in at least two, ideally three planes (third sagittal plane not shown in this figure). A syringe with vitamin E can also be used for lesion localization. Some MR systems are capable of localizing the lesion and planning of needle advancement based on a laser approach, similar to CT-guided procedures. Panel (c): The needle is visualized as susceptibility artifact during advancement based on T1 FSE sequence. Sequence acquisition in a single plane takes approximately 30 s. Panel (d): Since it is a gradient echo-based sequence, trueFISP can be acquired during advancement of the needle instead of the T1 FSE sequence, as shown in this image. The needle advancement was again visualized as susceptibility artifact. Compared to the T1 FSE sequence, the trueFISP sequence allowed for superior needle visualization secondary to increased susceptibility artifact while the needle tip was not as accurately visualized. Post sclerosant injection imaging of the same patient during MRI-guided sclerotherapy of temporal muscle VM. Panel (e): T1 FSE sequence demonstrated the injected sclerosant as a hyperintense area bordering the needle tip, while the needle was again shown as susceptibility artifact. This sequence allowed for assessment of sclerosant coverage of the VM lesion while excluding potential extravasation. Panel (f): As an alternative to the T1 FSE sequence, a T1 gradient echo (VIBE) sequence can be obtained that similarly demonstrated the needle as susceptibility artifact and the injected sclerosant as a hyperintense area bordering the needle tip. Similar to the T1 FSE sequence, the VIBE sequence also evaluated lesion coverage and exclusion of contrast extravasation. Compared to the T1 FSE sequence, VIBE has a greater field of view and can be acquired with less time. On the other hand, the T1 FSE sequence has superior soft tissue contrast that results in more accurate localization of the distribution of the sclerosant. Panels (g) and (h): T1 FS post-treatment images following needle removal in axial and sagittal planes, respectively. The sclerosant contrast mixture was shown within the VM component located in the right temporal muscle. There is no evidence of local extravasation.

Periprocedure medications

On the day of the procedure, we typically give a weight-based dose of intravenous (IV) cefazolin as antibiotic prophylaxis, within 60 min of initial puncture into the VM. Sclerotherapy, as a percutaneous procedure, contains a risk for inadvertent introduction of skin flora into the subcutaneous tissue, area surrounding the target VM, and even systemic vasculature. As a result, a one time pre-procedural prophylactic antibiotic dose is given. Ketorolac and/or dexamethasone are administered for pain control and anti-inflammatory properties.

Post-procedure the patients are admitted to the interventional radiology service for overnight observation. Adequate pain control is of utmost importance and we typically give a combination of acetaminophen and oxycodone per oral for pain management in the first five days post procedure. During the hospital stay, intravenous pain medications, such as hydromorphone hydrochloride may be considered if pain is not well controlled. However, patients must be switched to per oral regimen prior to discharge.

Preparation of sclerosant-gadolinium mixture

Gadolinium is mixed with the sclerosant in order to visualize the injection when using real-time MRI guidance. For low-flow VM, we use as ethanolamine oleate (EO) as the sclerosant. First, 5 mL of normal saline is mixed with 0.3 mL of Gadolinium. Consecutively, 0.3 mL of this saline-Gadolinium solution is mixed with every 2 mL of EO. For example, if a total 6 mL of EO is required (in the case of the patient shown in Figures 3 and 4), this sclerosant volume is mixed with 0.9 mL of the saline-Gadolinium solution.

Figure 3.

MRI characterization of VM in 16-year-old patient. Panels (a) and (b): T2 FS images demonstrated left lower lip VM abutting the gingiva in axial and sagittal planes, respectively. Panel (c): TWIST sequence revealed filling of the VM lesion in the lower lip during early to late venous phase, without evidence of arterial filling. Panel (d): Axial T1 post gadolinium imaging confirmed lesion enhancement that was consistent with VM.

Procedural steps with associated MRI sequences

The five procedural steps are illustrated based on two representative cases in Figures 2 and 4 after supine patient positioning in the MR magnet and general anesthesia, provided by the dedicated anesthesia team.

Initial three plane T2-weighted images (typically HASTE) are performed to localize the lesion. Based on these images, the ideal level within the lesion is determined to place the needle for sclerotherapy. This is performed in the following manner: real-time trueFISP (fast imaging steady-state precession) sequence is acquired in at least two (ideally three) planes centered at the predetermined ideal level of the lesion. The operator can then use either Vitamin E tablets or a saline-filled syringe to determine the needle entrance site at that level. The trueFISP images allow visualization of the vitamin E tablet or overlying syringe, since the liquid vitamin E and the saline appear hyperintense on this sequence. The operator then adjusts the position of the vitamin E tablets or saline-filled syringe while obtaining real-time trueFISP images until the optimal site for needle placement is obtained. Once the optimal site is achieved, the vitamin E tablets or syringe are removed and the site is then designated with an ink marker. The patient is withdrawn from the magnet bore. In Figure 2, a saline-filled syringe was used to determine the needle insertion site.

To gain access, needle insertion is started with imaging using either a T1 FSE or trueFISP sequence as a gradient echo sequence. In both sequences, the needle and needle tip are visualized secondary to susceptibility artifact. When comparing both sequences, the T1 FSE has a superior visualization of the needle tip, whereas in the trueFISP sequence, the needle trajectory is better seen due to stronger susceptibility artifact.

The sclerosant injection is monitored using a T1 FLASH sequence in all three planes. The sclerosant-Gadolinium mixture is well visualized and the continuously increasing distribution of the mixture can be seen as a hyperintense area. If contrast extravasation is depicted, the injection should be stopped immediately. Extravasation is visualized on real-time T1-weighted imaging as hyperintense accumulation beyond the VM borders delineated on initial multi-plane T2-weighted imaging. There is particular concern when the extravasated hyperintensity is linear in distribution and disappears on consecutive real-time images. This may indicate extravasation of the sclerosant into surrounding vasculature and increased risk of non-target embolization.

Before removing the needle, either a T1 FSE or VIBE (gradient echo based sequence) is performed to assess whether coverage of the VM is felt to be sufficient and to rule out extravasation. In both sequences, the needle is again seen as susceptibility artifact. The VIBE sequence enables faster imaging with a larger field of view, whereas the T1 FSE sequence allows for superior visualization of the needle and tissue structures. At this point, the needle can be removed.

Immediate post-procedure imaging is performed using a T1 fat-saturated sequence in at least two (ideally three) planes to confirm sufficient coverage of the VM with the Gadolinium-sclerosant mixture and to rule out delayed extravasation around the low-flow VM.

Figure 4.

The same patient shown in Figure 3 – a-16 year-old patient with MRI-guided sclerotherapy of VM. Panels (a) and (b): VM was located within the lower lip as a hyperintense lesion, based on sagittal and axial real-time trueFISP. The trueFISP sequence should be performed in at least two, ideally three planes (third coronal plane not shown in this figure). The Vitamin E syringe used for planning of needle advancement can be appreciated as a subtle hyperintensity outside of the patient. On the axial image, the hand of the interventionalist is visualized anteriorly to the patient’s head. Panel (c): Axial T1 FLASH sequence during advancement of the needle into the VM. The needle tip within the VM lesion is shown as hypointense susceptibility artifact. During needle advancement, T1 FLASH images are typically acquired as a triplane sequence. Panel (d): Axial T1 FLASH sequence during sclerosant injection (Ethanolamine Oleate mixed with Gadolinium, as detailed in the methods) revealed enhancement in the presumed area of VM in the left lower lip. The needle was visualized as susceptibility artifact surrounded by the enhanced area. Panel (e): Post-treatment axial VIBE demonstrated enhancement in the presumed area of VM in the left lower lip and the needle is in the center of the enhancing area, seen as a “black dot” due to susceptibility artifact. There is a linear high signal focus anteriorly to the enhancing area, reflective of a small venous dysplastic component (draining vein) of the malformation. Panel (f): Post-treatment axial T1 FS again demonstrated the hyperintense area in the presumed location of VM in the left lower lip. The Gadolinium contrast and sclerosant mixture were represented by the hyperintense area within the VM; thus, confirming lesion coverage, including its anteriorly located dysplastic component. There is no evidence of the Gadolinium contrast and sclerosant mixture extravasation outside of the VM area.

Discussion

This technical development paper demonstrates real-time MRI-guided sclerotherapy as an effective single modality treatment approach for VM in the head and neck region. The evolving technique is feasible and safe based on our institutional experience.

The primary sclerotherapy safety concerns in low-flow VM are the possibility of local extravasation and/or systemic dissemination of the sclerosing agent due the potential communication between the VM and its draining venous system.⁵ To decrease the amount of potential extravasation, MRI is used for both pre-procedural evaluation of lesion anatomy and associated vasculature,⁵ as well as post-procedural assessment of treatment response.

The mainstay sequence for pre-procedural imaging is T2-weighted images to identify and characterize VM lesions as well as post Gadolinium images, including TWIST, to exclude feeding arteries and large draining veins.⁵ Pre-procedural imaging facilitates with the definition of the VM anatomy and boundaries as well as the delineation of potential sclerosant-contrast mixture extravasation. TWIST is a non-invasive three-dimensional subtraction MR angiography (MRA) sequence used to provide high temporal and spatial resolution outlining vasculature flow and hemodynamics following contrast administration.^18,19 It has been shown to be effective in the quantitative differentiation between low-flow venous malformations and vascular malformations with high-flow dynamics (e.g. arteriovenous malformations and arteriovenous fistula).²¹ The identification of flow characteristics is important as real-time MRI-guided sclerotherapy is used to treat only low-flow vascular malformations. At our institution, TWIST is a standard sequence integrated in the MR protocol for pre-procedural characterization of VM. In addition to TWIST, T2-weighted short tau inversion–recovery (STIR) imaging can be used to delineate VM with large vascular channels from those with smaller vascular channels.⁵ Immediate post-procedural MRI follow-up is performed to assess the sclerosant mediated inflammatory reaction^9,22 and consequent changes in volumetric size and perfusion characteristics of the target VM lesions.^9,10,23 The follow-up MRI, along with the clinical picture, determines the need for additional sclerotherapy sessions.¹⁰

In addition to pre- and post- procedural imaging, the accuracy of needle placement and resultant sclerosant delivery is important for preventing local and systemic sclerosant extravasation, which can lead to embolic events as well as a variety of adverse reactions depending on the sclerosant used. For MRI-guided sclerotherapy procedures conducted at our institution, we primarily use EO, a detergent used to induce thrombosis and epithelial damage in vascular malformations, and doxycycline for lymphatic malformations.²⁴ EO has been shown to be clinically effective in treating VM, with positive response rates ranging from 88–100% and a complete response rate of up to 93%.^24–26 Significant complications following EO-based sclerotherapy are reported in less than 5% of the cases and include cardiovascular collapse, laryngeal edema, trismus, anaphylaxis, intravascular hemolysis, hemoglobinuria, and skin necrosis.^{4,9,10,23,27,28} In addition to EO, Bleomycin may also be used as a sclerosant for VM sclerotherapy as it incites nonspecific inflammation leading to endothelial sclerosis.²⁹ Although Bleomycin has a VM positive response rate of up to 88%, only up to 57% of lesions experience complete response.^28,30,31 Bleomycin has a 6% complication rate, and its adverse effects include skin pigmentation, cellulitis, focal alopecia, and nausea and vomiting.^4,28 Despite its low complete response rate relative to EO, Bleomycin may be preferred in certain cases, such as intraorbital lesions or lesions compressing the airway, since it has been described to cause less swelling post procedure.^32,33 Finally, absolute ethanol is a highly potent sclerosing agent that may be used for treatment of large VM.^34–36 Studies have shown the VM positive response rate to absolute ethanol to be in the range of 84 to 100%.²⁸ Despite its high response rate, absolute ethanol has potential significant complications upon systemic administration including pulmonary hypertension, hyperthermia, arrhythmia, central nervous system depression, and hemoglobinuria.⁴ Based on our institutional experience, although absolute ethanol is a more potent sclerosant compared to EO and Bleomycin, we recommend the use of EO over absolute ethanol as it presents with less severe adverse effects (if they occur) compared to absolute ethanol while having a similar range of clinical response rates, particularly in the head and neck

A very limited number of studies have shown MRI-guided sclerotherapy for vascular malformations in the head and neck to be clinically feasible in terms of both relieving clinical symptoms, such as oral hemorrhage, pain, and cosmetic disfigurement, as well as improving patient function of mastication and speech.^10,23 In one study, a total of 14 sclerotherapy procedures were completed in 3 patients using a mixture of EO or sodium tetradecyl sulfate, another detergent, with gadopentetate dimeglumine contrast under the guidance of a continuous gradient echo MRI FISP sequence for needle advancement.²³ In this study, patients did not experience any significant complications and did not require corticosteroids to reduce inflammation. Furthermore, follow-up MR imaging demonstrated vascular malformation volume reduction in all patients.²³

In the second study, a total of 76 sclerotherapy procedures were completed in 15 patients with vascular malformations, with 64 procedures completed in 10 patients with vascular malformations in the head and neck. A contrast-sclerosant mixture of EO and gadopentetate dimeglumine was used with continuous MRI FISP guidance. On follow-up imaging, a decrease of target lesion volume was observed in all patients with a mean decrease of 67.21% post therapy completion.¹⁰ All patients noted successful treatment of oral bleeding and subjective cosmetic improvement. In addition, the procedure also addressed patient specific symptoms such as buccal swelling, pain, and mastication and speech impairment.¹⁰ Similar to the first study, none of the patients experienced significant procedural complications.¹⁰ For both studies, technical success was achieved in all cases, as a continuous MR FISP sequence was able to provide guidance of needle placement and sclerosant delivery without extravasation.^10,23

In addition to these two studies, a recent case series detailed the technical and clinical success of MRI-guided sclerotherapy for a total of 14 procedures completed in 5 patients with VM (four in the head and neck and one in the knee). These patients underwent sclerotherapy with absolute ethanol guided by continuous MRA at 1.8 s/ frame.³⁷ According to the study, continuous MRA provided a three-dimensional rotatable spatial resolution that allowed the depiction of both VM vascular flow and embolization following sclerosant delivery. In all procedures, VM lesions demonstrated decreased flow and size of surrounding vasculature without procedural complications.³⁷ The above studies and case series provide evidence that a single MRI modality technique can be used for pre-procedural VM visualization, real-time procedural guidance of needle placement and sclerosant delivery, as well as post-procedural assessment of sclerosant mediated inflammatory reaction and potential sclerosant extravasation.

Building on the feasibility of MRI-guided sclerotherapy, several recently published studies dealing with VM outside of the head and neck area have demonstrated the effectiveness of real-time MRI guided sclerotherapy for VM. In one study, 1.5 Tesla real-time MRI-guided sclerotherapy with a newly developed pulse sequence was shown to be successful in dealing with VM in the chest, abdomen, and pelvis.³⁸ The authors tested their approach in a swine model and four patients using sodium tetradecyl sulfate. This study was aimed to address two limitations of current MRI sequences for VM sclerotherapy treatment, namely: (I) real-time MR sequences were unable to provide flexible T2 contrast and sharpness necessary for tissue and needle visualization^39,40 and (II) diagnostic T2 sequences used for tissue and VM visualization did not have the acquisition speed compatible with real-time guidance³⁸ The authors developed a T2 MR sequence, namely T2-weighted interrupted balanced steady-state free precession (T2W-iSSFP), which enabled an adjustable T2 contrast to provide high quality imaging resolution for VM and visualization of superficial connective tissue while rendering image acquisition speed at an acceptable rate of 2.5–3.5 frames per second for real-time guidance. Identification of VM and needle localization was successful during sclerotherapy treatment using this newly developed T2W-iSSFP pulse sequence.³⁸

A further investigation dealing with real-time MRI-guided sclerotherapy for VM located in the foot, ankle, and elbow showed that 1.5 Tesla MRI-guided delivery of a solution of meglumine gadoterate contrast in 94% absolute ethanol sclerosant was effective for treatment of VM leading to subsequent symptomatic improvement.²² The authors reported a complication rate of 10% with one patient developing compartment syndrome that was managed with surgery and nine other patients who tolerated the procedure well without development of complications.²² The study was technically successful in all 10 patients as needle placement and sclerosant delivery was carried out under real-time MRI guidance without extravasation. In terms of clinical success, the target VM lesions were reduced in volume by a mean of 53% at 12 weeks post sclerotherapy. Correspondingly, 9 out of 10 patients reported improvement of symptoms, while three patients reported complete resolution of symptoms.²²

In line with our technical development paper, these above studies demonstrate that real-time MRI guidance is a feasible and clinically effective single modality technique for sclerotherapy of VM in the head and neck. Due to the superior spatial resolution of MRI for complex local anatomy, there is a clinical need for real-time MRI-guided sclerotherapy. The introduction of MR sequences capable for providing sufficient temporal resolution for real-time guidance (e.g. gradient echo imaging) has established the foundation of MRI-guided sclerotherapy. Additionally, real-time MRI-guided sclerotherapy has been shown to be feasible for lymphatic malformations of the head and neck in the pediatric population.⁴¹ The technical and clinical success demonstrated by the treatment of head and neck VM using real-time MRI guidance based on our institutional experience as illustrated in this technical development manuscript reinforces that real-time MRI-guided sclerotherapy is both an efficacious and safe treatment approach for low flow venous malformations.

Footnotes

Declaration of Conflicting Interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) received no financial support for the research, authorship, and/or publication of this article.

References

Dubois

Soulez

Oliva

et al.

Soft-tissue venous malformations in adult patients: imaging and therapeutic issues. Radiographics 2001; 21: 1519–1531.

Loose

. Surgical management of venous malformations. Phlebology 2007; 22: 276–282.

Zheng

Mai

Zhang

et al.

Guidelines for the treatment of head and neck venous malformations. Int J Clin Exp Med 2013; 6: 377–389.

Love

Hsu

. Low-flow vascular malformations of the head and neck: clinicopathology and image guided therapy. J NeuroIntervent Surg 2012; 4: 414–425.

Mulligan

Prajapati

HJS

Martin

et al.

Vascular anomalies: classification, imaging characteristics and implications for interventional radiology treatment approaches. Br J Radiol 2014; 87: 20130392–20130392.

Brouillard

Vikkula

. Genetic causes of vascular malformations. Hum Mol Genet 2007; 16: R140–R149.

Kondziella

Nordanstig

Molne

et al.

Neurological picture: cranial neuropathy in the blue rubber bleb nevus syndrome. J Neural Neurosurg Psychiatry 2010; 81: 1207–1208.

Weinstein

Chamlin

. Quality of life in vascular anomalies. Lymphat Res Biol 2005; 3: 256–259.

Boll

Merkle

Lewin

. MR-guided percutaneous sclerotherapy of low-flow vascular malformations in the head and neck. Magn Reson Imag Clin N Am 2005; 13: 595–600.

10.

Boll

Merkle

Lewin

. Low-flow vascular malformations: MR-guided percutaneous sclerotherapy in qualitative and quantitative assessment of therapy and outcome. Radiology 2004; 233: 376–384.

11.

Spence

Krings

TerBrugge

et al.

Percutaneous sclerotherapy for facial venous malformations: subjective clinical and objective MR imaging follow-up results. Am J Neuroradiol 2010; 31: 955–960.

12.

Donnelly

Adams

Bisset

. Vascular malformations and hemangiomas: a practical approach in a multidisciplinary clinic. Am J Roentgenol 2000; 174: 597–608.

13.

Shiels

Kang

Murakami

et al.

Percutaneous treatment of lymphatic malformations. Otolaryngology 2009; 141: 219–224.

14.

Donnelly

Bissett

Adams

. Combined sonographic and fluoroscopic guidance: a modified technique for percutaneous sclerosis of low-flow vascular malformations. Am J Roentgenol 1999; 173: 655–657.

15.

Shen

C-Y

M-C

Tyan

Y-S

et al.

Preliminary experience of percutaneous intralesional bleomycin injection for the treatment of orbital lymphatic–venous malformation refractory to surgery. Clin Radiol 2012; 67: 182–184.

16.

Harmoush

Chinnadurai

El Salek

et al.

Multimodality image-guided sclerotherapy of low-flow orbital vascular malformations: report of single-center experience. J Vasc Intervent Radiol 2016; 27: 987–995.

17.

Partovi

Kohan

Vercher-Conejero

et al.

Qualitative and quantitative performance of 18F-FDG-PET/MRI versus 18F-FDG-PET/CT in patients with head and neck cancer. Am J Neuroradiol 2014; 35: 1970–1975.

18.

Higgins

Koshy

Mitchell

et al.

Time-resolved contrast-enhanced MRA (TWIST) with gadofosveset trisodium in the classification of soft-tissue vascular anomalies in the head and neck in children following updated 2014 ISSVA classification: first report on systematic evaluation of MRI and TWIST in a cohort of 47 children. Clin Radiol 2016; 71: 32–39.

19.

Van der Woude

Verstraete

Hogendoorn

et al.

Musculoskeletal tumors: does fast dynamic contrast-enhanced subtraction MR imaging contribute to the characterization?

Radiology 1998; 208: 821–828.

20.

Flors L, Leiva-Salinas C, Maged IM, et al. MR imaging of soft-tissue vascular malformations: diagnosis, classification, and therapy follow-up. Radiographics 2011; 31: 1321–1340.

21.

Hammer

Uller

Manger

et al.

Time-resolved magnetic resonance angiography (MRA) at 3.0 Tesla for evaluation of hemodynamic characteristics of vascular malformations: description of distinct subgroups. Eur Radiol 2016; February: 1–10.

22.

Andreisek

Nanz

Weishaupt

et al.

MR imaging-guided percutaneous sclerotherapy of peripheral venous malformations with a clinical 1.5-T unit: a pilot study. J Vasc Intervent Radiol 2009; 20: 879–887.

23.

Lewin

Merkle

Duerk

et al.

Low-flow vascular malformations in the head and neck: safety and feasibility of MR imaging-guided percutaneous sclerotherapy – preliminary experience with 14 procedures in three patients. Radiology 1999; 211: 566–570.

24.

Alexander

McTaggart

Choudhri

et al.

Percutaneous sclerotherapy with ethanolamine oleate for venous malformations of the head and neck. J Neurointervent Surg 2013; 6: 691–694.

25.

Choi

Han

O-Ki

. Craniofacial cavernous venous malformations: percutaneous sclerotherapy with use of ethanolamine oleate. J Vascular 2002; 13: 475–482.

26.

Hoque

Das

. Treatment of venous malformations with ethanolamine oleate: a descriptive study of 83 cases. Pediat Surg Int 2011; 27: 527–531.

27.

Hashizume

Kitano

Yamaga

et al.

Haptoglobin to protect against renal damage from ethanolamine oleate sclerosant. Lancet 1988; 6: 340–341.

28.

Horbach

SER

Lokhorst

Saeed

et al.

Sclerotherapy for low-flow vascular malformations of the head and neck: a systematic review of sclerosing agents. J Plast Reconstruct Aesth Surg 2016; 69: 295–304.

29.

Blum

Carter

Agre

. A clinical review of bleomycin – a new antineoplastic agent. Cancer 1973; 31: 903–914.

30.

Spence

Krings

Terbrugge

et al.

Percutaneous treatment of facial venous malformations: a matched comparison of alcohol and bleomycin sclerotherapy. Head Neck 2011; 33: 125–130.

31.

Spence

Krings

TerBrugge

et al.

Percutaneous sclerotherapy for facial venous malformations: subjective clinical and objective MR imaging follow-up results. Am J Neuroradiol 2010; 31: 955–960.

32.

Vadlamudi

Gemmete

Chaudhary

et al.

Transvenous sclerotherapy of a large symptomatic orbital venous varix using a microcatheter balloon and bleomycin. J Neurointervent Surg 2016; 8: e30–e30.

33.

Paramasivam

Fay

Fifi

et al.

O-015 image guided bleomycin sclerotherapy for orbital lymphatic malformation. J Neurointerv Surg 2014; 6(Suppl 1): A8–A9.

34.

Burrows

Mason

. Percutaneous treatment of low flow vascular malformations. J Vasc Intervent Radiol 2004; 15: 431–445.

35.

Yakes

Luethke

Parker

et al.

Ethanol embolization of vascular malformations. Radiographics 1990; 10: 787–786.

36.

Rimon

Garniek

Galili

et al.

Ethanol sclerotherapy of peripheral venous malformations. Eur J Radiol 2004; 52: 283–287.

37.

Imbesi

Green

Cho

et al.

MR angiographic–guided percutaneous sclerotherapy for venous vascular malformations: a radiation dose-reduction strategy. Am J Neuroradiol 2016; 37: 205–209.

38.

Herzka

Gilson

et al.

MR-guided sclerotherapy of low-flow vascular malformations using T2-weighted interrupted bSSFP (T2W-iSSFP): comparison of pulse sequences for visualization and needle guidance. J Magn Reson Imag 2015; 41: 525–535.

39.

Patel

Klufas

Alberico

et al.

Half-fourier acquisition single-shot turbo spin-echo (HASTE) MR: comparison with fast spin-echo MR in diseases of the brain. Am J Neuroradiol 1997; 18: 1635–1640.

40.

Herborn

Vogt

Lauenstein

et al.

MRI of the liver: can true FISP replace HASTE?

J Magn Reson Imag 2003; 17: 190–196.

41.

Partovi

Vidal

et al.

Real-time MRI guided percutaneous sclerotherapy of low-flow head and neck lymphatic malformations in the pediatric population – a stepwise approach. Pediatr Radiol 2017; 47: 755–760.