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Magnetic Resonance Imaging of the Soft Tissue Vascular Anomalies in Torso and Extremities in Children: An Update With 2014 International Society for the Study of Vascular Anomalies Classification

Snyder, Elizabeth, MD*; Puttgen, Kate, MD; Mitchell, Sally, MD; Ahlawat, Shivani, MD§; Tekes, Aylin, MD*

Journal of Computer Assisted Tomography: March/April 2018 - Volume 42 - Issue 2 - p 167–177
doi: 10.1097/RCT.0000000000000675
Review Article

Vascular anomalies can occur anywhere in the body, and the majority present in the pediatric population. Accurate classification is essential for proper clinical evaluation, particularly because multidisciplinary care is often required. The International Society for the Study of Vascular Anomalies classification offers a comprehensive classification for all subspecialties. In this review article, we present a magnetic resonance imaging protocol with exemplary cases of the most common types of vascular anomalies in the pediatric trunk and extremities using the current International Society for the Study of Vascular Anomalies classification.

From the *Department of Radiology, Division of Pediatric Radiology and Pediatric Neuroradiology, Department of †Dermatology and ‡Radiology, Division of Interventional Radiology, and §Department of Radiology, Division of Musculoskeletal Radiology, Johns Hopkins University School of Medicine, Baltimore, MD.

Received for publication June 7, 2017; accepted June 8, 2017.

Correspondence to: Elizabeth Snyder, MD, The Russell H. Morgan Department of Radiology and Radiological Science, Division of Pediatric Radiology, The Johns Hopkins School of Medicine, Charlotte R. Bloomberg Children's Center, Sheikh Zayed Tower, Room 4174, 1800 Orleans St, Baltimore, MD 21287-0842 (e-mail: esnyde17@jhmi.edu).

The authors declare no conflict of interest.

The topic of vascular anomalies is one of the many areas in medicine that suffered from decades of confusing terminology. A clinically relevant, comprehensive classification system that can serve different medical subspecialties, such as the International Society for the Study of Vascular Anomalies (ISSVA) classification, is necessary to provide common language among caregivers.

Vascular anomalies comprise a wide variety of disorders, including both vascular tumors and malformations, which typically present during childhood and may involve any part of the body. Vascular anomalies are the most common soft tissue masses in pediatric patients.1,2 Because the various vascular anomalies may have vastly different morbidities and treatment options, accurate description and classification of these lesions is essential for patient management.3,4 In addition, because these lesions may be complex and involve multiple compartments of the body, treatment often requires multidisciplinary teams, and common language is essential for communication.

Evaluation of vascular anomalies begins with a thorough clinical history and targeted physical examination. Given the overlapping clinical and imaging findings in some vascular anomalies, accurate classification is often best provided by clinicians who are experienced in the evaluation of these patients. In many cases, the correct diagnosis can be reached based on history and physical appearance alone. Imaging is used in cases where the diagnosis may be uncertain, or to evaluate extent for treatment planning purposes. Ultrasonography is often used for first-line imaging of vascular anomalies, particularly because of its wide availability including for examinations performed at the bedside, and its lack of ionizing radiation. Although ultrasound is frequently able to correctly characterize the anomaly, it is limited to evaluation of superficial lesions and may not evaluate the lesion's full extent. Computed tomography has limited use in the evaluation of vascular anomalies, because the imaging findings on computed tomography are often nonspecific and because of the risk of ionizing radiation in pediatric patients, especially considering the potential need for multiple imaging studies for diagnosis and follow-up.

Magnetic resonance imaging (MRI) offers the highest soft tissue resolution providing detailed anatomical information with multiplanar imaging capabilities and is useful in cases in which the diagnosis is uncertain or in which the extent of the lesion must be delineated. Conventional contrast-enhanced MRI and dynamic time-resolved magnetic resonance angiogram (MRA) can accurately define the extent and characteristics of these anomalies, facilitating the accurate diagnosis and classification. Furthermore, MRI may be used to evaluate the response to treatment overtime. The 2014 ISSVA classification provides a comprehensive classification system that is accepted worldwide and can be used among all medical specialists who may encounter these children. In this article, we provide a summary of the updated 2014 ISSVA classification system and present exemplary cases of common pediatric vascular anomalies in the torso and extremities with a state-of-the-art MRI/MRA imaging protocol.

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Classification System

In 1982, Mulliken and Glowacki5 published the landmark article for the classification of vascular anomalies based on their endothelial characteristics. On the basis of these histologic findings, these complex anomalies were classified as hemangiomas vs malformations and became the basis for the 1996 ISSVA classification system. The 1996 ISSVA classification further stratified the anomalies between vascular tumors, such as hemangiomas, and malformations,6 and was significant in that vascular tumors were expanded beyond hemangiomas to include tumors such as congenital hemangiomas and kaposiform hemangioendotheliomas. Vascular malformations were further divided based on the speed of blood flow within the masses: slow-flow, high-flow, and mixed malformations.

Further understanding of the genetic basis, response to treatment, and description of additional unique pathologies necessitated the updated ISSVA classification (Table 1).7,8 Vascular tumors were subdivided based on their biological behavior: benign, locally aggressive, or malignant. Vascular malformations were further subdivided as to whether they were “simple” or “combined” malformations and if they were associated with other anomalies.

TABLE 1

TABLE 1

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MRI Protocol

After results from a careful clinical history and physical examination are obtained, imaging may be required in cases where the diagnosis is unclear. When an MRI is required, an appropriate protocol is essential for differentiating these lesions and making the correct diagnosis.9–11

In our institution, we obtain a contrast-enhanced conventional MRI and dynamic contrast-enhanced MRA. Conventional MRI includes triplanar T2-weighted images with fat saturation, precontrast axial T1-weighted images, and postcontrast triplanar T1-weight images with fat saturation.

Because flow characteristics (arterial, venous, both arterial and venous, none) are essential to the classification of these vascular anomalies, we also obtain dynamic postcontrast images. Our temporal resolution (1–1.5 seconds) allows for evaluation of the arterial and venous phases.12,13 Dynamic postcontrast images have been shown to be useful in distinguishing among vascular malformations.13–16

To further complement the contrast-to-noise ratio in the dynamic MRA and postcontrast T1 weighted images, we use a blood-pool contrast agent, gadofosveset trisodium (Ablavar; Lantheus, Billerica, MA), which remains predominantly confined to the blood pool with little tissue enhancement and extravasation.17 We use a 0.03-mmol/kg body weight, one-third of the dose of a regular gadolinium contrast agent, with a contrast bolus rate of 1.5 mL/s.

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VASCULAR TUMORS

Benign Vascular Tumors

Infantile Hemangioma

Infantile hemangiomas (IHs) are the most common tumor in infants and present as a nascent patch on the skin at birth or within the first few weeks of life.5,18,19 They undergo rapid proliferation in the first months of life, and most growth occurs by 3 months of age, with growth typically completed in more than 80% of infants by 5 months of age.5,20,21 Infantile hemangiomas undergo spontaneous regression over a period of years, with more than 90% of involution occurring by age 3.5 to 4 years.5,20,22,23 Although hemangiomas most commonly present in the facial region, they may present anywhere in the body.20,24 On pathology, IH stain positive for immunologic markers such as glucose transporter 1, which is a unique feature that differentiates them from other vascular tumors and vascular malformations.25

Although the diagnosis of IH can almost always be made based on clinical appearance and history, MRI may be required when the presentation is atypical or in cases when the lesions is located deep and cannot be properly evaluated with physical examination or ultrasound. In complex cases, MRI may be required to evaluate the extent of the lesion before treatment and to evaluate treatment response. The MRI appearance of an IH depends on the stage of proliferation of the tumor at the time of imaging. They are often imaged in the proliferative phase, where they appear as solid, well-circumscribed expansile masses, which appear hyperintense on T2-images and typically isointense on T1-weighted images (Fig. 1). Conventional postcontrast images demonstrate homogenous, avid enhancement with an arterial feeder. Dynamic contrast-enhanced images demonstrate the mass avidly enhancing during the arterial phase (Fig. 1). Involuted IHs, if imaged to assess for treatment response, may demonstrate T1-hyperintense fatty deposition and will seem to enhance less avidly than proliferative hemangiomas.

FIGURE 1

FIGURE 1

Understanding the typical growth pattern of hemangiomas is essential to reach the proper imaging diagnosis. Because infantile and congenital hemangiomas may have overlapping imaging features in infancy, the differential diagnosis between infantile and congenital hemangiomas is often made in retrospective fashion after assessing the temporal evolution of the mass. Finding typical imaging characteristics of a proliferative hemangioma in an older child, when IH would have involuted, should prompt consideration of an alternative diagnosis. In such cases, major differential considerations include rhabdomyoscarcoma, rhabdoid tumor, or congenital hemangioma. Rhabdomyosarcoma often appears as a heterogeneous mass with more irregular borders, often with surrounding soft tissue edema and heterogeneous enhancement. In cases where atypical imaging findings are encountered, biopsy may be required for definitive evaluation.

Most IHs do not require intervention because they will undergo regression and may be observed on a clinical basis.26 Treatment may be required if complications develop, such as bleeding or ulceration, or treatment can be performed electively to reduce potential disfigurement.22,26,27 The mainstay of medical treatment of IH is propranolol, whereas those with contraindications to β-blocker treatment may receive a corticosteroid.22,27,28 Laser or surgical therapy may also be used in certain cases.27–29

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LUMBAR Syndrome

Segmental IHs, those that typically appear as broad geographic plaques on the skin surface, may be associated with an underlying syndrome involving extracutaneous abnormalities. Infantile hemangioma in the lumbosacral region, perineum, or lower extremities may be associated with a range of extracutaneous malformations such as urogenital, anorectal, and osseous malformations (Fig. 1). This syndrome has been referred to as LUMBAR, PELVIS, or SACRAL syndrome.30,31 When imaging patients with segmental hemangiomas in the lower half of the body, consideration must be given to the possibility of LUMBAR syndrome. Magnetic resonance imaging and MRA of the entire abdomen and pelvis as well as MRI of the spine may be needed in these cases.30

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Congenital Hemangiomas

Congenital hemangiomas are less common than IH and, unlike IH, are present and fully formed at birth.32 There are 3 main subtypes of congenital hemangioma, rapidly involuting (RICH), noninvoluting (NICH), and partially involuting (PICH) congenital hemangiomas.7 None of these 3 types of congenital hemangiomas stain positive for glucose transporter 1, in contrast to IH.32 Like IH, congenital hemangiomas are most common in the head and neck, but may also be seen in the trunk or extremities.33 Diagnosis of congenital hemangiomas must be made in light of the typical clinical history and physical appearance because imaging findings may overlap with IH (Fig. 2).34 Although the differentiation among the subtypes is made based on clinical characteristics, MRI may be used in the pretreatment evaluation of NICH or PICH. On MRI, both RICH and NICH appear as solid, vascular masses, which may contain flow voids and may demonstrate solid or heterogeneous enhancement.34

FIGURE 2

FIGURE 2

Treatment of NICH or incompletely involuted congenital hemangiomas may not be required if they are asymptomatic. If residual lesions are large and/or symptomatic, they may require surgical excision.35 Differentiating between congenital and IHs is vital because congenital hemangiomas do not respond to β-blocker therapy.

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Locally Aggressive Vascular Tumors

Kaposiform Hemangioendothelioma

Kaposiform henagioendothelioma is a locally aggressive vascular tumor that may be associated with Kassibach-Merrit phenomenon, a consumptive coagulopathy marked by profound thrombocytopenia and consumptive coagulopathy.36–38 Cutaneous involvement is common, but these tumors usually also involve the deeper tissues and can be found in the trunk, extremities, or retroperitoneum.36,37,39,40 On MRI, unlike IH, kaposiform henagioendothelioma typically appears as an aggressive mass, crossing over multiple tissue planes with ill-defined boundaries, and is associated with cutaneous thickening and subcutaneous fat stranding and edema.40,41 Kaposiform henagioendothelioma may also cause osseous destruction, detectable by MRI, which is not typical in IH.41

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Other Vascular Tumors

Multiple additional vascular tumors, such as tufted angioma, hemangioendothelioma, pyogenic granuloma, and angiosarcoma, may rarely be encountered. Magnetic resonance imaging has been shown to be helpful in distinguishing between benign and malignant vascular tumors, with malignant tumors typically demonstrating early arterial enhancement, with peripheral edema and enhancement with possible involvement of the adjacent neurovascular bundles.42,43 The role of MRI, used in conjunction with clinical findings, is primarily to raise the possibility of a malignancy, and biopsy is required for definitive diagnosis and for treatment planning.

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VASCULAR MALFORMATIONS

Simple Vascular Malformations

Vascular malformations are true malformations that arise from the maldevelopment of the embryonic vascular system.44 Simple malformations are described based on the dominant vessel type involved.

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Venous Malformations

Venous malformations (VMs) are the most common vascular malformation and are commonly seen in the trunk and extremities.45 They are present at birth, although may not be noted until later in life, and grow commensurately or may grow faster than the child. On the basis of direct percutaneous phlebography appearances, Puig et al46 initially classified VMs by the type of venous drainage. This has important implications regarding treatment and prognosis.46,47

  • Type I: isolated malformations without venous drainage
  • Type II: drainage into normal veins
  • Type III: drainage into dysplastic veins
  • Type IV: lesions consist of venous ectasia
  • Type I and II VMs respond best to sclerotherapy, with lower number of treatment sessions, whereas types III and IV are associated with more complications related to systemic venous.

On conventional MRI, VMs are predominantly T2-hyperintense lesions that may demonstrate variable morphology. They may be remarkably infiltrative (Fig. 3), without respecting tissue planes, or less commonly, they may appear predominantly saccular (Fig. 4). The infiltrative lesions are often interspersed with fibrofatty tissue (Fig. 5). Internal T2-hypointense foci may be seen, which are phleboliths (Figs. 3 and 5). Fluid-fluid levels and hematocrit levels, although more common in lymphatic malformations (LMs), may also be a component of VM, which reflect slow vascular flow. On postcontrast images, these lesions demonstrate variable but often heterogeneous contrast enhancement. Dynamic contrast-enhanced MRA demonstrates progressive contrast enhancement in the venous phase, clearly differentiating them from high-flow vascular malformations.

FIGURE 3

FIGURE 3

FIGURE 4

FIGURE 4

FIGURE 5

FIGURE 5

Although treatment of these lesions may be dependent on location, percutaneous sclerotherapy is the mainstay of treatment of symptomatic lesions. Sometimes, sclerotherapy can be the first stage for a surgically resectable VM.

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Lymphatic Malformations

Lymphatic malformations are cystic dilated lymphatic channels and spaces separated by fibrous septa, which do not communicate with normal lymphatic channels. Similar to VMs, there are different morphologic subtypes, including macrocystic, microcystic, and mixed. Lymphatic malformations may occur anywhere in the body.48

The typical MRI appearance of a macrocystic LM is a large, lobulated multicystic mass (Fig. 6). The cystic spaces are T2 hyperintense and may show variable T1 intensity depending on the degree of internal hemorrhagic or proteinaceous content. Although these lesions may contain fluid-fluid levels or internal hemorrhage, these findings are not specific to LMs but rather slow-flow malformations. On postcontrast images, LMs do not show any internal enhancement but may show minimal peripheral enhancement of the cyst walls or septa. Dynamic postcontrast imaging will show no arterial or venous enhancement, clearly differentiating them from arterial or VMs.

FIGURE 6

FIGURE 6

Lymphatic malformations can be subclassified as microcystic, macrocystic, or mixed type based on the size of the cyst lumens, a distinction that may affect choice of treatment. On imaging, microcystic LMs may appear as multiple small cysts, or the cysts may be too small to resolve by MRI (Fig. 7). They appear as hyperintense lesions on T2-weighted images. Although microcystic LMs typically do not demonstrate postcontrast enhancement, because the cyst wall and septa may enhance, these lesions may also show mild diffuse enhancement. Macrocystic LMs demonstrate larger cystic components, usually of variable sizes. Mixed LMs show components of both macrocystic and microcystic LMs.41

FIGURE 7

FIGURE 7

Treatment of LMs depends on the location and type of lesion. Macrocystic LMs are more easily targeted with percutaneous sclerotherapy with ultrasound guidance. Doxycyclin and bleomycin are the most commonly used agents. Percutaneous sclerotherapy can often replace surgery in treating LM in the trunk and extremities.49,50 Medications, such as sildenafil and sirolimus, have also been shown to be effective in the treatment of LM and, more recently, VM.51–53 Medical therapy is currently aimed at patients with highly infiltrative, large space-occupying, predominantly microcystic LMs.

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Capillary Malformations

Capillary malformations are a group of abnormal vessels located in the dermis. Because the diagnosis is virtually always made based on clinical appearance, imaging, in particular MRI, is not required in most cases. In rare cases, capillary malformations may be associated with other anomalies as part of a syndrome. In such cases, MRI may be used to evaluate for additional anomalies.

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Arteriovenous Malformations

Arteriovenous malformations (AVMs) are abnormal connections between arteries and veins without an intervening normal capillary bed. They may be located anywhere, most commonly in the head and neck, whereas the second most common location is the upper extremity.54

Classic conventional MRI findings are a tangle of hypointense, serpigineous flow voids on T2-weighted images (Fig. 8). There may be increased T2 signal in the surrounding soft tissue because of alterations in perfusion. Dynamic contrast images are essential to the diagnosis of AVMs because these lesions demonstrate early arterial enhancement from arterial feeders with early venous drainage. A nidus consisting of a tangle of abnormal vessels is also typically seen (Fig. 8). Arteriovenous malformations are the most aggressive of all vascular malformation and bony destruction can be seen (Fig. 9).

FIGURE 8

FIGURE 8

FIGURE 9

FIGURE 9

Treatment of AVMs consists of embolization, with or without surgical excision.54

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Combined Malformations

Combined vascular malformations are defined by ISSVA by the presence of more than 1 vessel type.7 Any combination of vessels may be present, and the anomalies are named and classified based on the involved vessels. Magnetic resonance imaging can aid in the classification of these lesions, particularly to determine the presence of a high-flow component.

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SYNDROMES

Vascular malformations may be associated with other anomalies, which, although rare, can be classified into a variety of characteristic syndromes. These are typically distinguished based on the type of vascular malformation and the presence or absence of tissue overgrowth, which may include soft tissue, bony, and/or fatty components. Recent advances in genetics have significantly aided in differential diagnosis and classifications of these complex syndromes.

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Klippel-Trénaunay Syndrome

Klippel-Trénaunay syndrome (K-T syndrome) typically consists of a capillary malformation (port-wine stain) with an underlying VM and/or LM, as well as bony and soft tissue hypertrophy typically affecting one extremity or one-half of the body.55,56 There may involvement of the lower abdomen or pelvis, including involvement of the lower gastrointestinal tract or the bladder.55 The clinical presentation may be quite variable among different patients with this syndrome, and the etiology is currently unknown but has recently been linked to mutations in the PIK3CA gene.57–60

Conventional MRI in these patients will vary depending on the components of the vascular malformation, variously demonstrating components of capillary malformation, venous malformation, and LMs, associated with dilated, abnormal veins in the affected extremity with associated soft tissue and osseous hypertrophy (Fig. 10). Dynamic contrast-enhanced images show enhancement within the venous phase for the VMs and pericystic enhancement for the LMs, without any arterial enhancement. The absence of arterial enhancement is essential to the diagnosis because Parkes-Weber syndrome, in contrast, is an overgrowth syndrome associated with multiple small high-flow malformations such as AVMs, usually in the lower extremity.

FIGURE 10

FIGURE 10

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Parkes-Weber Syndrome

Parkes-Weber syndrome is another overgrowth syndrome defined by a capillary malformation associated with soft tissue and osseous hypertrophy.61,62 In contrast to K-T syndrome, Parkes-Weber is associated with underlying high-flow vascular malformations, particularly AV fistulas. In most cases, a single lower extremity is involved.61,62 Although the diagnosis is often suggested based on clinical history, MRI can be used to define the extent of involvement before treatment.

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CLOVES Syndrome

CLOVES (Congenital Lipomatous asymmetric Overgrowth of the trunk with lymphatic, capillary, venous, and combined-type Vascular malformations, Epidermal naevi, Scoliosis/Skeletal and spinal anomalies) is an overgrowth syndrome associated with both low-flow and high-flow vascular malformations as well as lipomatous overgrowth of the trunk.60,63,64 These patients have mutations in the PIK3CA gene, which is thought to increase phosphoinositide-3-kinase activity.65 Magnetic resonance imaging demonstrates soft tissue overgrowth and increased fat deposition in the chest, abdomen, and/or pelvis and will show a vascular anomaly, which may have capillary, venous, lymphatic, arterial, or combined components.63,64 Dynamic contrast-enhanced MRA findings will vary depending on the type of vascular lesion.

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Provisionally Unclassified Vascular Anomalies

A few vascular anomalies remain unclassified by ISSVA because their underlying pathogenesis is incompletely understood.8 These include such entities as angiokeratoma, verrucous hemangioma, and kaposiform lymphangiomatosis (KLA). This presence of this category highlights the need to further study these complex anomalies to potentially provide better categorization and treatments. Although we highlight one of these entities below for educational purposes, these rare entities are best evaluated and treated at experienced, specialty centers.

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Kaposiform Lymphangiomatosis

Kaposiform lymphangiomatosis is a diffuse lymphatic abnormality with distinct histopathological findings, differentiated from generalized lymphatic anomaly by the existence of a significant coagulopathy.66,67 Although this is a rare syndrome, the radiologic features may be distinctive and the radiologist may be first to suggest the diagnosis. Typical MRI findings include diffusely infiltrative increased T2 signal soft tissue in the mediastinum or along bronchovascular bundles.65–67 Retroperitoneal, visceral, and bony lesions are also common.67 Minimal contrast enhancement can be seen because of their microcystic nature.65–67 Interestingly, contrast enhancement is quite strong in bone involvement in KLA (Fig. 11).

FIGURE 11

FIGURE 11

The hallmark pathologic findings include abnormal, dilated lymphatic spaces associated with clusters of spindle cells.66,67 Abnormal lymphatics are seen most commonly in the chest, but also frequently in the retroperitoneum.67 Treatment of complex, microcytic, diffusely infiltrative LMs is quite challenging because percutaneous embolization is not an option. Recently, medical treatment with immunomodulatory drugs such as sirolimus has been reported, which offers KLA patients a potential treatment option.68 Poor prognosis is often related to pulmonary involvement of the malformation.66,67,69

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CONCLUSIONS

In this article, we described our state-of-the art MRI protocol designed for imaging of soft tissue vascular anomalies in the pediatric body and extremities, highlighting the most critical conventional and dynamic MRI imaging features following 2014 ISSVA classification. Multidisciplinary approach is critical for these patients; thus, using a common language as offered by ISSVA is essential to avoid miscommunication, misdiagnosis, and delayed or inappropriate treatment.

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Keywords:

MRI; vascular malformations; vascular anomalies; hemangioma

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