MR Imaging of Soft-Tissue Vascular Malformations: Diagnosis, Classification, and Therapy Follow-up 1

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1 Note: This copy is for your personal non-commercial use only. To order presentation-ready copies for distribution to your colleagues or clients, contact us at VASCULAR/INTERVENTIONAL RADIOLOGY 1321 MR Imaging of Soft-Tissue Vascular Malformations: Diagnosis, Classification, and Therapy Follow-up 1 ONLINE-ONLY CME See /rg_cme.html LEARNING OBJECTIVES After completing this journal-based CME activity, participants will be able to: List the clinical and MR imaging features that aid in diagnosis of vascular anomalies and their proper classification. Discuss optimized MR imaging protocols for evaluation of vascular anomalies. Describe posttherapy appearances of vascular anomalies at MR imaging. INVITED COMMENTARY See discussion on this article by Coldwell (pp ). Lucía Flors, MD Carlos Leiva-Salinas, MD Ismaeel M. Maged, MD, MSc Patrick T. Norton, MD Alan H. Matsumoto, MD John F. Angle, MD Hugo Bonatti, MD Auh Whan Park, MD Ehab Ali Ahmad, MD Ugur Bozlar, MD Ahmed M. Housseini, MD Thomas E. Huerta, RRT (MR) Klaus D. Hagspiel, MD Vascular malformations and tumors comprise a wide, heterogeneous spectrum of lesions that often represent a diagnostic and therapeutic challenge. Frequent use of an inaccurate nomenclature has led to considerable confusion. Since the treatment strategy depends on the type of vascular anomaly, correct diagnosis and classification are crucial. Magnetic resonance (MR) imaging is the most valuable modality for classification of vascular anomalies because it accurately demonstrates their extension and their anatomic relationship to adjacent structures. A comprehensive assessment of vascular anomalies requires functional analysis of the involved vessels. Dynamic time-resolved contrast material enhanced MR angiography provides information about the hemodynamics of vascular anomalies and allows differentiation of high-flow and low-flow vascular malformations. Furthermore, MR imaging is useful in assessment of treatment success and establishment of a long-term management strategy. Radiologists should be familiar with the clinical and MR imaging features that aid in diagnosis of vascular anomalies and their proper classification. Furthermore, they should be familiar with MR imaging protocols optimized for evaluation of vascular anomalies and with their posttreatment appearances. Supplemental material available at RSNA, 2011 radiographics.rsna.org Abbreviations: AVF = arteriovenous fistula, AVM = arteriovenous malformation, FLASH = fast low-angle shot, GRE = gradient-echo, MIP = maximum intensity projection, SE = spin-echo, SSFP = steady-state free precession, STIR = short τ inversion-recovery, 3D = three-dimensional, TWIST = dynamic time-resolved with interleaved stochastic trajectories, VIBE = volumetric interpolated breath-hold examination RadioGraphics 2011; 31: Published online /rg Content Codes: 1 From the Departments of Radiology and Medical Imaging (L.F., C.L.S., I.M.M., P.T.N., A.H.M., J.F.A., A.W.P., E.A.A., A.M.H., T.E.H., K.D.H.) and Surgery (H.B.), University of Virginia Health System, 1215 Lee St, Box , Charlottesville, VA 22908; Department of Radiology, Suez Canal University Hospitals, Ismailia, Egypt (I.M.M., A.M.H.); Department of Surgery, Vanderbilt Medical Center, Nashville, Tenn (H.B.); Department of Radiology, El Minia University, El Minia, Egypt (E.A.A.); and Department of Radiology, Gulhane Military Medical Academy, Etlik, Ankara, Turkey (U.B.). Presented as an education exhibit at the 2009 RSNA Annual Meeting. Received October 1, 2010; revision requested February 21, 2011; final revision received May 4; accepted May 9. For this journal-based CME activity, the authors (L.F., C.L.S., I.M.M., H.B., A.W.P., E.A.A., U.B., A.M.H., T.E.H.), editor, and reviewers have no relevant relationships to disclose. P.T.N. and K.D.H. receive grant support from Siemens. A.H.M. is on the advisory boards of and consults for Boston Scientific, Bard, and Siemens and receives research grants from Talecris, Gore, Cook, Elbit, Medtronic, and Endologix. J.F.A. consults for Terumo. Use of extracellular gadolinium contrast media for MR angiography constitutes off-label use. Address correspondence to K.D.H. ( kdh2n@virginia.edu). RSNA, 2011

2 1322 September-October 2011 radiographics.rsna.org Introduction Vascular malformations and tumors comprise a wide, heterogeneous spectrum of lesions that involve all parts of the body and can cause significant morbidity and even mortality in both adults and children. Vascular lesions represent the most common cause of pediatric soft-tissue masses (1). In the past, this subject has been obscured by considerable confusion due to use of an unclear nomenclature. The term hemangioma has been applied generically to vascular lesions of differing cause and clinical behavior (2). Occasionally, confusion about terminology and imaging guidelines continues to be responsible for improper diagnosis and subsequent treatment (3). Since treatment strategy depends on the type of malformation, correct diagnosis and classification of a vascular anomaly are crucial. In most patients, diagnosis and proper classification of soft-tissue vascular malformations and tumors are achieved on the basis of an accurate clinical history and physical examination results. Imaging should be targeted at specific information required for treatment planning, especially in cases of unclear classification or extension of the lesion. Gray-scale ultrasonography (US) coupled with color Doppler US provides information about the degree of vascularity of a lesion. US was traditionally considered the imaging modality of choice for initial assessment and characterization of soft-tissue lesions of presumed vascular origin (4), mainly because of its ability to allow differentiation between hemangiomas and vascular malformations (5,6). However, US has the disadvantages of a limited field of view, restricted penetration, and operator dependency (7). Magnetic resonance (MR) imaging in combination with MR angiography performed with intravenous administration of gadolinium-based contrast material has an important role in evaluating the extent of lesions, particularly deeper lesions, and their relationship to adjacent structures. The recently introduced three-dimensional (3D) dynamic time-resolved MR angiography technique provides valuable information about the hemodynamics of vascular lesions; thus, MR imaging also aids in diagnosis and classification in clinically uncertain cases. In this article, we review the classification of vascular anomalies and their principal clinical features, with a focus on vascular malformations and tumors of developmental origin that occur in soft tissue. In addition, we describe an optimized MR imaging technique for evaluation of these lesions and the different MR imaging features that aid in diagnosis, proper classification, and treatment planning. Finally, we describe the appearances of these lesions after treatment. Classification of Vascular Anomalies Several classification systems have been proposed for vascular anomalies. In 1982, Mulliken and Glowacki (8) described the most helpful and widely accepted classification. It is a biologic classification based on cellular turnover, histologic features, natural history, and physical findings (8). They classified vascular anomalies as either hemangiomas or vascular malformations (8). Hemangiomas are benign vascular tumors of infancy and childhood that consist of cellular proliferation and hyperplasia and are characterized by a rapid early proliferative stage and a later involuting stage (4,7,8). In comparison, vascular malformations arise from dysplastic vascular channels and exhibit normal endothelial turnover, growing commensurately with the child without regression (4,7,8). According to the preponderant vascular channels, vascular malformations are classified as venous, lymphatic, capillary, arterial, or combined. To reclassify vascular anomalies into a system directly related to investigation and treatment, in 1993 Jackson et al (9) proposed a radiologic classification formulated in combination with the biologic classification of Mulliken and Glowacki (8). Jackson et al (9) subcategorized vascular malformations according to their flow dynamics as low-flow or high-flow malformations. In 1996, these systems were adopted and expanded by the International Society for the Study of Vascular Anomalies (10). Two categories of vascular anomalies are considered: vascular tumors (with infantile hemangioma being the most common) and vascular malformations. Vascular malformations are subcategorized according to their flow dynamics as low-flow malformations (venous, lymphatic, capillary, capillary-venous, and capillary-lymphatic-venous) and high-flow malformations (arteriovenous malformations [AVMs] and arteriovenous fistulas [AVFs]); thus, any malformation with an arterial component is considered high flow, while those without an arterial component are considered low flow. The classification of vascular anomalies and their main clinical and MR imaging features are summarized in Table 1.

3 RG Volume 31 Number 5 Flors et al 1323 Table 1 Clinical and MR Imaging Features of Vascular Anomalies Vascular Anomalies Clinical Features MR Imaging Features* Treatment Vascular tumors Infantile hemangioma Low-flow vascular malformations Venous Lymphatic Capillary High-flow vascular malformations AVM Proliferating phase: occurs in 1st few weeks of life; rapidly growing lesion; strawberry-like, pulsatile, warm mass Involuting phase: grayish dark red mass; complete regression at age 7 10 y Occurs in childhood or early adulthood; blue, soft, compressible, nonpulsatile mass; grows proportionally with the child without regression Occurs in childhood; smooth, noncompressible, rubbery mass; grows proportionally with the child without regression Occurs at birth; cutaneous red discoloration; grows proportionally with the child without regression Occurs in childhood or early adulthood; red, pulsatile, warm mass with a thrill; grows proportionally with the child without regression Proliferating phase: well-defined lobulated mass, low SI on T1WI, high SI on T2WI, flow voids on SE images, no perilesion edema, early homogeneous enhancement Involuting phase: fat replacement (high SI on T1WI), decreased enhancement Septated lobulated mass without mass effect, phleboliths (low SI), fluid-fluid levels, low SI on T1WI, high SI on T2WI, no flow voids on SE images, infiltrates tissue planes, surrounding edema possible, no arterial or early venous enhancement, slow gradual enhancement, diffuse enhancement on delayed images Septated lobulated mass, fluid-fluid levels, low SI on T1WI, high SI on T2WI, no flow voids on SE images, infiltrates tissue planes; if macrocystic, has rim and septal enhancement; if microcystic, no significant or slight diffuse enhancement Skin-thickness lesion No well-defined mass; enlarged feeding arteries and draining veins; flow voids on SE images; infiltrates tissue planes; early enhancement of enlarged feeding arteries and nidus with shunting to draining veins *SE = spin-echo, SI = signal intensity, T1WI = T1-weighted images, T2WI = T2-weighted images. None (propranolol) Percutaneous sclerotherapy Percutaneous sclerotherapy None Transarterial embolization MR Imaging Technique MR imaging is the most valuable modality for classification of vascular anomalies (11). It allows one to define the extension of vascular lesions and their anatomic relationship to adjacent structures (4), thus providing important information for therapy planning. The selection of coils depends on the size and location of the lesion, but generally the smallest surface coil that covers the entire lesion should be chosen. We use a torso phased-array coil for imaging the chest, abdomen, and pelvis and specialized peripheral phased-array coils for imaging the extremities. If the lesion is palpable or visible, placement of a skin marker over the area of clinical concern is often useful. Images should be acquired in at least two orthogonal planes (1).

4 1324 September-October 2011 radiographics.rsna.org Figure 1. AVM of the arm in a 21-year-old woman. Images from arterial phase (a) and venous phase (b) maximum intensity projection (MIP) 3D contrast-enhanced MR angiography and dynamic time-resolved MR angiography with interleaved stochastic trajectories (TWIST MR angiography) (c) show an AVM in the right arm. Owing to the highflow characteristics of the malformation, arterial and venous discrimination is not possible with single-phase 3D contrast-enhanced MR angiography. TWIST MR angiography permits acquisition of images with a temporal resolution of 2.4 seconds (images in 40 phases were acquired in this second acquisition), with excellent depiction of the hemodynamics of the vascular malformation (Movie E1 [online]). The TWIST images show significantly dilated arteries (arrow in c) and veins (arrowheads in c) throughout the right upper extremity, with early filling of the extensive nidus as well as early venous shunting. Note that images at two stations were acquired in c. For multistation examinations with the TWIST sequence, bolus chase imaging is not possible and each station should be imaged in a separate examination. Therefore, separate contrast material injections and subject repositioning for each station are mandatory. Examination protocols should include SE or fast SE T1-weighted imaging for basic anatomic evaluation and fat-suppressed fast SE T2- weighted or short τ inversion-recovery (STIR) imaging to assess extension of the lesion. The high accuracy of heavily T2-weighted imaging in demonstrating the extent of vascular malformations has been described before, and this technique is widely used in clinical practice (12 14). Contrast material enhanced MR angiography, performed with a 3D T1-weighted fast gradientecho (GRE) sequence with intravenous administration of gadolinium-based contrast material, is also needed to evaluate perfusion of the lesion. Usually, imaging is performed in the arterial phase and several venous phases. Images are also obtained before contrast material administration for posterior subtraction of contrast-enhanced images and 3D reformation. Comprehensive assessment of vascular anomalies requires functional analysis of the involved vessels; this is not completely possible with the sequences mentioned earlier. For this purpose, dynamic time-resolved MR angiography has become an essential tool. This technique, in which 3D fast GRE imaging is applied, uses creative acquisition of k-space, oversampling the center of k-space relative to the periphery and thus sharing portions of k-space to create the images. This technique permits acquisition of images with high temporal and spatial resolution. Whereas conventional contrast-enhanced MR angiography allows acquisition of one 3D dataset every 15 seconds, dynamic time-resolved MR angiography allows acquisition of one 3D dataset every 2 seconds. This high temporal resolution enables (a) clear separation of arterial inflow from venous drainage and detection of early venous shunting, (b) acquisition of information about the contrast material arrival time (defined

5 RG Volume 31 Number 5 Flors et al 1325 Table 2 MR Imaging Protocol for 3-T Systems Parameter Single-Shot SSFP STIR T1W Fast SE 3D TWIST MRA 3D GRE T1W FLASH* 3D FS T1W VIBE* TR/TE (msec) 4.74/ /50 600/ / / /1.17 Flip angle (degrees) Section thick ness (mm) NSA NA 1 1 Matrix , , FOV (mm) No. of sections , 96 96, 192 Imaging time (sec) , 31 20, 204 Note. FOV = field of view, FS = fat-suppressed, MRA = MR angiography, NA = not applicable, NSA = number of signals acquired, TE = echo time, T1W = T1-weighted, TR = repetition time. *Postcontrast images were obtained with the same sequence. Inversion time = 220 msec. These data refer to breath-hold acquisitions in the abdomen. For anatomic regions where breath-hold acquisition is not necessary, we routinely increase the resolution. as the interval between the onset of enhancement and the maximal percentage of enhancement in the vessels) and flow direction, and (c) reduction of motion artifacts (7,14) (Fig 1). Hence, excellent depiction of the architecture and hemodynamic properties of vascular malformations can be achieved (15), yielding clinically important data about feeding and draining vessels that is crucial for therapy planning (12). The technique has been proved to allow discrimination between low-flow and high-flow malformations (15,16). GRE T2*-weighted images can be used in some cases to demonstrate calcification or hemosiderin, as well as high-flow vessels. On GRE images, absence of signal in the blood vessel suggests a low-flow malformation (4,17) whereas high-flow vessels have high signal intensity. At our institution, the standard examination protocol has a total table time on the order of 45 minutes. It includes the following sequences: (a) fast imaging with steady-state free precession (SSFP) in the axial, coronal, and sagittal planes, to cover the entire anatomy in all three planes; (b) coronal and axial STIR imaging; (c) coronal and axial fast SE T1-weighted imaging; (d) coronal 3D TWIST MR angiography; (e) spoiled GRE 3D T1-weighted imaging with fast low-angle shot (FLASH), performed without contrast material as well as with contrast material (contrastenhanced MR angiography) in the arterial phase and early, intermediate, and late venous phases; and (f) unenhanced as well as delayed contrastenhanced fat-suppressed 3D T1-weighted imaging with volumetric interpolated breath-hold examination (VIBE) in the axial or coronal plane or both. To facilitate analysis of images from contrastenhanced MR angiography, subtraction as well as 3D reformation techniques including multiplanar reformation, MIP, and volume rendering are used as deemed necessary. Detailed imaging parameters are listed in Table 2 for 3-T systems and in Table 3 for 1.5-T systems. We use 0.4 ml per kilogram of subject body weight of an extracellular gadolinium compound, such as gadobenate dimeglumine (Multihance; Bracco Diagnostic, Milan, Italy) or gadopentetate dimeglumine (Magnevist; Bayer Schering Pharma, Berlin, Germany). One-third of the dose is used for TWIST MR angiography; the remainder is used for contrast-enhanced MR angiography. Acquisition of the TWIST MR angiography images is synchronized with the start of an intravenous injection of 0.13 ml per kilogram of weight of the contrast material at a rate of 2 ml/ sec followed by a saline flush. We usually acquire images in 45 phases with a temporal resolution of approximately 2 seconds per phase.

6 1326 September-October 2011 radiographics.rsna.org Table 3 MR Imaging Protocol for 1.5-T Systems Parameter Single-Shot SSFP STIR T1W Fast SE 3D TWIST MRA 3D GRE T1W FLASH* 3D FS T1W VIBE* TR/TE (msec) 4.3/ /27 611/14 NA 3.32/ /1.61 Flip angle NA (degrees) Section thick NA ness (mm) NSA NA 1 1 Matrix NA , , , FOV (mm) NA No. of sections NA 64, 80 44, 192 Imaging time (sec) NA 14, 26 24, 232 Note. FOV = field of view, FS = fat-suppressed, MRA = MR angiography, NA = not applicable, NSA = number of signals acquired, TE = echo time, T1W = T1-weighted, TR = repetition time. *Postcontrast images were obtained with the same sequence. Inversion time = 150 msec. These data refer to breath-hold acquisitions in the abdomen. For anatomic regions where breath-hold acquisition is not necessary, we routinely increase the resolution. Figure 2. Proliferating infantile hemangioma in a 1-year-old infant. (a) Photograph shows a lobulated mass in the right breast with superficial involvement, which causes its strawberry-like appearance. (b) Axial T1-weighted image shows the well-defined lobulated hypointense mass in the right breast. Signal voids in the lesion (arrow) represent fast-flow vessels. No perilesion edema is identified. (c) On a STIR image, the mass is hyperintense. Arrow = signal voids in the lesion. (d) Image from arterial phase 3D MR angiography shows characteristic early enhancement of the lesion without arteriovenous shunting.

7 RG Volume 31 Number 5 Flors et al 1327 Information obtained with TWIST MR angiography can be used to calculate the contrast material injection delay for contrast-enhanced MR angiography. A dose of 0.27 ml per kilogram body weight of the contrast material is then injected, again with a saline flush and an injection rate of 2 ml/sec. Images are acquired in the arterial phase and early, intermediate, and delayed venous phases, with a 30-second delay between each phase. In our opinion, the essential set of sequences is as follows: SE or fast SE T1-weighted imaging, fat-suppressed fast SE T2-weighted or STIR imaging, 3D dynamic time-resolved MR angiography and contrast-enhanced MR angiography, and postcontrast fat-suppressed T1-weighted imaging. Although 3-T and 1.5-T systems provide similar image quality, our preference for using the 3-T system is based on the availability of the sequences at our institution. VIBE (Siemens Healthcare) (also known as LAVA [GE Healthcare] and THRIVE [Philips Healthcare]) is a 3D fat-suppressed T1-weighted GRE sequence that allows short acquisition times in comparison with the relatively long imaging times of traditional SE or fast SE sequences without degrading image quality. There are two main differences between this sequence and the standard T1-weighted GRE sequence used for contrast-enhanced MR angiography: nearly isotropic resolution and reduced flip angle. These differences permit improvement in the signal from background tissue structures, and therefore high-spatial-resolution images of both the vascular system and the surrounding soft tissues can be obtained. The delayed (5 10 minutes after contrast material injection) contrast-enhanced 3D T1-weighted VIBE sequence is useful to appreciate the drainage of the malformation in the venous system and to evaluate very-low-flow malformations. Children under 5 years of age usually require sedation to tolerate the MR imaging examination. We use a contrast material dose of 0.1 mmol per kilogram body weight of gadopentetate dimeglumine (Magnevist). Warming the contrast material before injection may reduce the likelihood of awakening a sedated subject. Because the contrast material dose is very small in small children, the injection volume can be increased by diluting the contrast material with sterile saline up to 100%. These larger volumes ensure the prolonged bolus needed for the longer acquisition times of MR angiography. Hemangiomas The term hemangioma is used to designate a group of benign endothelial neoplasms that includes common hemangioma of infancy or infantile hemangioma, congenital hemangioma, and kaposiform hemangioendothelioma (1). Infantile Hemangioma Clinical Characteristics. Infantile hemangioma is the most common vascular tumor of infancy (1), with a prevalence of about 2% 3% in all children (15) and a female predominance (female-to-male ratio, 3 5:1) (7,18). The prevalence is even higher (10%) in premature infants of very low birth weight (15). The most common location is the face and neck (60% of cases), followed by the trunk (25%) and extremities (15%) (1,7,19). Infantile hemangiomas are normally not yet visible at birth but manifest during the 1st few weeks as rapidly growing lesions (15), often becoming evident by 3 months of age (1) as subcutaneous bluish red masses that resemble the surface of a strawberry (Fig 2). Reflecting the characteristic high-flow component of this phase, they show bruit, pulsatility, and warmth (7). After a proliferating phase in the 1st few months, a slow but constant regression (involuting phase) can be seen, with the process usually being completed by 7 10 years of age (1). During that time, the hemangioma changes color to grayish dark red, loses its toughness, and alters in shape, developing into a fibrofatty residuum (10,15). Histologically, in the proliferating phase, hemangiomas consist of hyperplastic proliferating endothelial cells that form syncytial masses with increased turnover and increased number of mast cells. Later, the involuting phase shows progressive perivascular deposition of fibrofatty tissue and thinning of the endothelial lining (7,19). In most cases, no treatment is required because of spontaneous involution. Treatment may be needed when the hemangioma is symptomatic or occurs in regions where there is possible secondary loss of function or lifetime aesthetic impairment. Medical treatment is usually attempted first, with propranolol used as a firstline therapy with excellent results (4,20). When medical treatment is ineffective, embolization or surgery is required (4).

8 1328 September-October 2011 radiographics.rsna.org MR Imaging Features. The diagnosis is made clinically in most cases. MR imaging may be required in clinically uncertain cases, in deep hemangiomas with normal overlying skin, when evaluation of extension is necessary, for guiding therapy, and to evaluate response to treatment. MR imaging features of infantile hemangiomas differ according to the biologic phase. In the proliferating phase (Fig 2), they typically appear as well-defined lobulated masses with high signal intensity on T2-weighted images and intermediate signal intensity on T1-weighted images. Perilesion edema should not be seen (4). Flow voids may be visible within high-flow feeding arteries and draining veins on SE images and appear as high signal intensity on GRE images. After injection of gadolinium contrast material, there is early intense and uniform enhancement (1). Despite the high-flow nature of the hemangioma during this phase, arteriovenous shunting is not seen, whereas it is in AVMs (7). During the involuting phase, appearances are more varied and heterogeneous (21). As increasing amounts of fat replace the tumor, foci of increased signal intensity are noted in the lesion on T1-weighted images and less avid enhancement is seen (1). If perilesion edema is present, other tumoral lesions (eg, sarcoma, neuroblastoma, hemangiopericytoma, fibrosarcoma, rhabdomyosarcoma) must be ruled out (4). Therefore, all lesions with unusual imaging or clinical findings should be evaluated with biopsy (22 24). Congenital Hemangioma Clinical Characteristics. A much less common vascular tumor, congenital hemangioma is fully grown and clinically evident at birth without gender predominance (1,7). Two subtypes are identified: rapidly involuting congenital hemangiomas completely regress during the first 2 years of life, whereas noninvoluting congenital hemangiomas demonstrate growth proportional to that of the child without regression (1,4). MR Imaging Features. MR imaging findings are mainly similar to those of infantile hemangioma (1,4,7). Vascular aneurysms, intravascular thrombi, an increased venous component, and arteriovenous shunting are some distinctive findings (4). Kaposiform Hemangioendothelioma Clinical Characteristics. Kaposiform hemangioendothelioma is a vascular neoplasm of borderline malignancy and intermediate aggressiveness (7). It can metastasize to regional lymph nodes, although this is rare (1). It commonly manifests at birth (7) and is most often located in the extremities, trunk, or head and neck (1,7). In contrast to infantile hemangioma, spontaneous regression without treatment is uncommon (1). Kaposiform hemangioendothelioma is associated with Kasabach-Merritt syndrome, a coagulopathy characterized by profound thrombocytopenia (1,7). MR Imaging Features. Ill-defined margins, smaller feeding and draining vessels (7), involvement of multiple tissue planes, hemosiderin deposits, and destructive changes are some distinctive MR imaging findings from those of infantile hemangioma (1). Vascular Malformations Vascular malformations are congenital anomalies and are thus present at birth, although not always evident. They usually grow proportionally with the child and show no regression. Their growth can be exacerbated due to hormonal changes during puberty or pregnancy or as a result of thrombosis, infection, trauma, or incomplete treatment (7). Unlike hemangiomas, they may be infiltrative and usually involve multiple tissue planes. As discussed earlier, vascular malformations are classified into high flow and low flow. The latter category accounts for more than 90% of vascular lesions outside the central nervous system (7). This differentiation based on flow dynamics is vital to planning surgical or image-guided treatment procedures. In addition to differentiation between low-flow and high-flow malformations, the other main goal of MR imaging of peripheral vascular malformations is to accurately define the anatomic extent of the lesion. Complex-combined malformations are found in some syndromes: Klippel-Trenaunay, Sturge- Weber, Parkes Weber, blue rubber bleb, Proteus, and Maffucci syndromes, among others (4). Low-Flow Vascular Malformations Venous Malformation Clinical Characteristics. Venous malformations are the most common peripheral vascular malformation (22,25 27). They are usually located in the head and neck (40% of cases), trunk (20%), and extremities (40%) (19), where they account for almost two-thirds of vascular malformations (22,26).

9 RG Volume 31 Number 5 Flors et al 1329 Figure 3. Blue rubber bleb nevus syndrome in a 32-year-old woman with an extensive subcutaneous and intramuscular venous malformation. (a) STIR image shows the extent of the venous malformation, which appears as a hyperintense, multilobulated, septated mass involving the subcutaneous tissue and muscles of the right upper extremity, right chest wall, and right pleural space. Multiple phleboliths (arrows) are seen as signal voids in the lesion. The presence of any pathologic arterial inflow was excluded with contrast-enhanced MR angiography. (b) Delayed contrast-enhanced fat-suppressed 3D VIBE T1-weighted image shows diffuse nodular enhancement of the venous malformation. A venous malformation is defined as a simple malformation with slow flow and an abnormal venous network (27). They are often misnamed cavernous hemangiomas. Histologically, they are composed of small and large dysplastic, postcapillary, thin-walled vascular channels with sparse smooth muscle and variable amounts of hamartomatous stroma, thrombi, and phleboliths (14,19). The dysplastic venous channels usually connect with adjacent physiologic veins via narrow tributaries (22). A mural muscular anomaly is probably responsible for the gradual expansion of these lesions (2,27). Venous malformations are already present at birth, but patients usually have symptoms in late childhood or early adulthood. The clinical presentation depends on the depth and extent of the lesion. When they involve the skin and subcutaneous tissues, venous malformations appear as faint blue, soft, easily compressible, and nonpulsatile masses (13,19,22). They characteristically enlarge with the Valsalva maneuver and in dependent positions and decompress with extremity elevation and local compression. Venous malformations may permeate across tissue planes and invade multiple adjacent tissues (fat, muscle, tendon, bone). Other problems related to venous malformations include pain, impaired mobility, and skeletal deformity (14,19,22). Venous malformations or combined lymphaticvenous malformations are found in blue rubber bleb nevus, Proteus, and Maffucci syndromes. Blue rubber bleb nevus syndrome is a familial condition characterized by development of multiple cutaneous, musculoskeletal, and gastrointestinal venous malformations (Fig 3). Patients can present with chronic blood loss and intermittent small bowel obstruction due to chronic bleeding, intussusception, or volvulus of gastrointestinal venous malformations (4,21). Proteus syndrome includes cutaneous and visceral combined lymphaticvenous malformations with multiple subcutaneous hamartomas, pigmented nevi, hemihypertrophy, hand or foot overgrowth, bone exostoses, and lipomatosis (4,14). Maffucci syndrome consists of diffuse enchondromatosis involving the phalanges of the hands and feet in association with multiple venous or lymphatic malformations (4).

10 1330 September-October 2011 radiographics.rsna.org Figure 4. Posterior cervical venous malformation in a 41- year-old woman with severe pain and right upper extremity numbness. (a) Sagittal T1- weighted image shows a hypointense lobulated mass involving the posterior cervical triangle. (b) On a STIR image, the venous malformation is hyperintense and has a multilocular appearance due to abnormal venous lakes separated by thin hypointense septa. MR angiography showed no arterial or early venous enhancement. (c) Delayed contrast-enhanced fat-suppressed T1-weighted image shows diffuse homogeneous enhancement of the lesion. (d) Image obtained with direct percutaneous injection of contrast material also shows diffuse homogeneous enhancement of the lesion. MR Imaging Features. Venous malformations are usually septated lesions with intermediate to decreased signal intensity on T1-weighted images and increased signal intensity on T2-weighted and STIR images (Fig 4). Occasionally, hemorrhage or high protein content may cause internal fluidfluid levels. In cases of thrombosis or hemorrhage, heterogeneous signal intensity can be observed on T1-weighted images. The best clue for identification of a venous malformation is the presence of phleboliths (15), which appear as small lowsignal-intensity foci with all pulse sequences (Fig 3). Fat-suppressed T2-weighted and STIR images have been shown to exquisitely define the extent of venous malformations (4,14) (Figs 3, 4). In terms of treatment decisions, recognizing whether the lesion is a low-flow vascular malformation is more important than determining ex-

11 RG Volume 31 Number 5 Flors et al 1331 actly whether the lesion is predominantly venous, lymphatic, or capillary (12,16,22,23). Diagnosis of a low-flow malformation is based on the absence of flow voids on SE images. Occasionally, low-signal-intensity striations, septa, thrombosed vessels, or phleboliths may simulate flow voids on cross-sectional images. Contrast-enhanced and GRE images may be helpful in distinguishing these other causes of low signal intensity from flow-related signal voids. Phleboliths and calcifications typically appear as signal voids with all pulse sequences, whereas signal voids related to high flow demonstrate enhancement and appear as high-signal-intensity foci on GRE images. Venous malformations are characterized by lack of arterial and early venous enhancement and absence of enlarged feeding vessels or arteriovenous shunting. They typically show slow gradual filling with contrast material and may demonstrate characteristic nodular enhancement of tortuous vessels on delayed venous phase images (Fig 3) (12). Low-flow vascular malformations, mainly venous malformations, have a contrast material rise time of about 90 seconds, significantly higher than that of high-flow AVMs (16). Delayed postcontrast T1-weighted images of venous malformations usually show diffuse enhancement of the slow-flowing venous channels (7,28) (Fig 4). Demonstration of a connection between a malformation and the deep venous system is useful for planning treatment, since such a finding increases the risk of deep venous thrombosis (28). The delayed contrast-enhanced sequence is perfectly suited for this purpose (4). Together with lack of evident venous drainage, well-defined lesion margins at MR imaging have been shown to be a predictor of good outcome after percutaneous sclerotherapy (15,29,30). Although venous malformations can be associated with surrounding edema or fibrofatty stroma, they rarely appear masslike (14,23,28). Accordingly, lesions with unusual clinical and imaging features should be evaluated with biopsy (23,28). Lymphatic Malformation Clinical Characteristics. Lymphatic malformations are the second most common type of vascular malformation after venous malformations (31). They are usually located in the neck (70% 80%), especially in the posterior cervical triangle, and in the axillary region (20%) and rarely found in the extremities (7,19). Lymphatic malformations consist of chylefilled cysts lined with endothelium (7,19). They result from sequestered lymphatic sacs that fail to communicate with peripheral draining channels (19). Cystic malformations can be divided into macrocystic and microcystic types. The latter are composed of multiple cysts smaller than 2 mm in a background of solid matrix, whereas macrocystic lesions have larger cysts of variable sizes (7,32). Lymphatic malformations are commonly associated with other vascular malformations (1). Most lymphatic malformations are discovered in the first 2 years of life. Clinically, they manifest as smooth soft-tissue masses with a rubbery consistency. Microcystic lymphatic malformations tend to permeate the skin, whereas macrocystic lymphatic malformations manifest as smooth, translucent multiple masses under normal skin (15). Unlike venous malformations, they are noncompressible. Diffuse soft-tissue thickening and surrounding lymphedema may occur locally with microcystic lesions (7). MR Imaging Features. Lymphatic malformations are usually seen as lobulated, septated masses with intermediate to decreased signal intensity on T1-weighted images and increased signal intensity on T2-weighted and STIR images (Figs 5 7). Internal fluid-fluid levels are common (Fig 5). Lymphatic malformations tend to be infiltrative, permeate across fat planes, and involve multiple tissues (7,14). There is usually no significant enhancement of microcystic lymphatic malformations (7,21) (Fig 6), whereas macrocystic lymphatic malformations exhibit only rim and septal enhancement (Fig 5) and no central filling of the cystic structures is expected after contrast material injection (7,22). Occasionally, microcystic lymphatic malformations or combined lymphatic-venous malformations may show diffuse enhancement, which is due to septal enhancement of the small, nonperceptible cysts in microcystic lymphatic malformations or enhancement of the venous component in mixed malformations (Fig 7). This appearance may render them indistinguishable from venous malformations (22,26).

12 1332 September-October 2011 radiographics.rsna.org Figure 5. Macrocystic lymphatic malformation in a 6- month-old infant with a swollen mass in the submandibular triangle. (a) T1-weighted image shows a welldefined, multilobulated, septated mass that is mildly hyperintense relative to the muscles. The increased signal intensity is most likely related to a high proteinaceous component. Note the fluid-fluid level (arrow) in the posterior component of the mass. (b) On a STIR image, the mass is highly hyperintense. Arrow = fluid-fluid level. (c) Axial gadolinium-enhanced fat-suppressed T1- weighted image shows rim and septal enhancement (arrowheads) with no enhancement of the lymph-filled spaces. Arrow = fluid-fluid level. Capillary Malformation Clinical Characteristics. Capillary malformations are present at birth in 0.3% of children (7) and demonstrate cutaneous red discoloration. They are predominantly localized in the head and neck region (15,33). Capillary malformations are areas of congenital ectasia of thinwalled small-caliber vessels of the skin. Although typically confined to the dermis or mucous membranes, they may also be the hallmark of more complex anomalies such as Sturge-Weber, Klippel-Trenaunay, and Parkes Weber syndromes (7,15). Symptoms in these patients are the result of deeper associated malformations (8,22). Sturge-Weber syndrome involves a unilateral capillary malformation in the distribution of the trigeminal nerve with ipsilateral leptomeningeal malformation, atrophy, and calcification of the subjacent cerebral cortex and malformation of the choroid (4,14). Klippel-Trenaunay syndrome involves a combined capillary-venous malformation of the trunk and extremities in association with limb overgrowth (4,14). Parkes Weber syndrome involves a cutaneous capillary malformation with limb hypertrophy in combination with AVFs and congenital varicose veins (4). MR Imaging Features. MR imaging is not usually required because the diagnosis is made clinically. MR imaging findings of capillary malformations are subtle, with skin thickening and occasional increased subcutaneous thickness as the only findings (7,22,34). MR imaging may be required to evaluate possible associated underlying disorders. Capillary-Venous Malformation Clinical Characteristics. Capillary-venous malformations are combined low-flow malformations formed from dysplastic capillary vessels and enlarged postcapillary vascular spaces.

13 RG Volume 31 Number 5 Flors et al 1333 Figure 6. Microcystic lymphatic malformation of the forearm in a 5-year-old girl. (a) Coronal STIR image shows a hyperintense, lobulated, septated mass (arrowheads) involving the subcutaneous tissue of the distal left forearm and hand. (b) Delayed contrast-enhanced 3D VIBE image shows no significant enhancement of the mass, a finding characteristic of a microcystic lymphatic malformation. Figure 7. Microcystic lymphatic malformation in a 5-year-old boy. (a) Axial STIR image shows a hyperintense, septated subcutaneous mass in the medial aspect of the left knee (arrows). Contrast-enhanced MR angiography showed no arterial or venous enhancement. (b) Delayed contrast-enhanced 3D VIBE image shows mildly increased signal intensity due to enhancement of the septa (arrowheads) between the microcysts.

14 1334 September-October 2011 radiographics.rsna.org Figure 8. Capillary-venous malformation of the calf in a 32-year-old woman. (a) Axial T2-weighted image shows hyperintense ill-defined subcutaneous involvement (arrows) of the lateral aspect of the distal left lower extremity. (b) Image from MR angiography shows characteristic early diffuse enhancement of the lesion (*) and early venous shunting (arrows). Note the absence of dilated arteries and draining veins. Figure 9. AVM of the proximal left forearm in a 26-year-old woman. (a) Fast SE (STIR) image shows the enlarged high-flow feeding arteries, draining veins, and nidus of the AVM as signal voids (arrows). (b) GRE (SSFP) image shows the enlarged high-flow feeding arteries, draining veins, and nidus as high-signal-intensity foci (arrows). (c) MIP image from arterial phase 3D MR angiography shows the arterial supply of the AVM, which is primarily via a tortuous and dilated ulnar artery (arrow), as well as early filling of the nidus (*) and draining veins (arrowheads).

15 RG Volume 31 Number 5 Flors et al 1335 Figure 10. Complex AVM affecting the entire right lower extremity in a 34-year-old woman. (a) MIP image from arterial phase 3D MR angiography shows enlarged vasculature and early venous shunting (arrows) with filling of the nidus (arrowheads), findings most apparent near the popliteal artery and along the medial aspect of the foot. (b) T1-weighted image shows femoral bone marrow involvement as decreased signal intensity (arrow). Atrophy of the right leg due to muscular fatty atrophy was likely secondary to arterial steal phenomenon. during the proliferating phase, infantile hemangiomas are also considered high-flow lesions. AVFs are formed by a single vascular channel between an artery and a vein, whereas AVMs consist of feeding arteries, draining veins, and a nidus composed of multiple dysplastic vascular channels that connect the arteries and veins, with absence of a normal capillary bed (14,19,22). Arteriovenous Malformation Clinical Characteristics. AVMs are already present at birth in the early quiescent stage (15) but do not usually become evident until childhood or adulthood. Like other vascular malformations, they generally increase proportionally in size as the child grows, with growth being exacerbated due to hormonal changes during puberty or pregnancy (14) or as a result of thrombosis, infection, or trauma (22). Owing to their high blood flow, they manifest as a red, pulsatile, warm mass with a thrill and may lead to bone overgrowth, arterial steal phenomenon, and cutaneous ischemia (15). Ulceration and hemorrhage may be seen in later stages (15). MR Imaging Features. Imaging findings may be nondistinguishable from those of venous malformations. Dynamic contrast-enhanced MR imaging can be useful for this purpose, as capillary-venous malformations typically show early homogeneous enhancement (Fig 8), whereas only delayed enhancement is seen in venous malformations (7,35). High-Flow Vascular Malformations High-flow malformations make up approximately 10% of malformations in the extremities (23) and include AVMs and AVFs. Keep in mind that, MR Imaging Features. MR imaging findings include high-flow serpentine and enlarged feeding arteries and draining veins (Figs 1, 9), which appear as large flow voids on SE images or high-signal-intensity foci on GRE images (Fig 9), with absence of a well-defined mass. Intraosseous extension of the lesion can be seen as decreased marrow signal intensity on T1-weighted images (15) (Fig 10). Areas of high signal intensity on T1-weighted images may represent

16 1336 September-October 2011 radiographics.rsna.org Figure 11. MR imaging appearance of a venous malformation in the calf after percutaneous sclerotherapy. (a) STIR image obtained 2 months after treatment shows loss of the typical lobulated appearance of the malformation and significant hyperintense perilesion inflammation as well as edema along the intermuscular fascia (arrowheads). The sclerosed portions of the lesion have low signal intensity (arrows). (b) Arterial phase image from gadolinium-enhanced 3D MR angiography shows slight enhancement (*). (c) Venous phase image from gadolinium-enhanced 3D MR angiography shows significant diffuse enhancement (*). (d) Venous phase source image from 3D MR angiography shows absence of enhancement in the central portion of the lesion (arrowheads) and significant enhancement along the periphery of the lesion and in surrounding soft tissues (arrows), findings consistent with thrombosis of the treated areas of the malformation, perilesion inflammation, and inflammation of the remaining areas of the malformation. (e) STIR image obtained 5 months after treatment shows slight shrinkage of the malformation with decreased signal intensity compared with that in a and absence of fluid in the intermuscular fascia. areas of hemorrhage, intravascular thrombosis, or flow-related enhancement (21). Gadolinium enhancement is useful in evaluating the feeding arteries and draining veins. The dynamic opacification of the AVM is well assessed by using time-resolved dynamic 3D MR angiography (Fig 1), with a contrast material rise time of 5 10 seconds. Early venous filling is typically seen in AVMs (Figs 1, 9, 10). Arteriovenous Fistula Congenital AVFs, which usually occur in the head and neck, are different from the more common acquired AVFs, which are mostly the consequence of an iatrogenic or traumatic penetrating injury. MR imaging shows the arterial and venous components as large signal voids on SE images or high-signal-intensity foci on GRE images, without a well-defined mass (1). Chronic secondary AVFs can simulate AVMs because they may have such strong flow that more proximal supplying arteries and distal draining veins also enlarge (36). Posttreatment Appearances Infantile hemangiomas tend to spontaneously involute; thus, no treatment is usually required. However, vascular malformations should be treated to prevent permanent functional and aesthetic impairment. The treatment strategy, which often consists of multiple treatment sessions, depends on the type of malformation in terms of flow dynamics and includes both minimally invasive and surgical interventions. For low-flow vascular malformations, the treatment of choice is percutaneous sclerotherapy; for high-flow lesions, it is transarterial embolization (4,7,19), with subsequent surgical resection occasionally being necessary. Percutaneous sclerotherapy is not effective for high-flow lesions because the infused agents are rapidly

17 RG Volume 31 Number 5 Flors et al 1337 Figure 12. MR imaging appearance of a posterior cervical venous malformation after several sessions of percutaneous sclerotherapy (same patient as in Fig 4). MR images show significant shrinkage of the malformation with a subcutaneous scar, which has low signal intensity on a sagittal STIR image (arrow in a) and absence of gadolinium enhancement on a delayed contrast-enhanced fat-suppressed T1-weighted image (arrow in b). The remaining portions of the malformation appear as hyperintense foci on the STIR image (arrowheads in a) and as enhanced areas on the delayed contrast-enhanced fat-suppressed T1-weighted image (arrowheads in b). washed away from the lesion (7). MR imaging is an excellent tool for assessment of treatment results and establishment of the long-term management strategy (37). Venous Malformations Ethanol causes almost instantaneous denudation of endothelium, intense inflammatory reaction, and thrombosis of the malformation associated with significant swelling (15,33,38). During the following weeks, fibrosis develops and progressive shrinking of the malformation is observed (15). A delay of up to several months is necessary to evaluate the therapeutic response after sclerotherapy, allowing time for the transient inflammatory response to resolve (27). At MR imaging, venous malformations after sclerotherapy demonstrate heterogeneous signal intensity on both T1-weighted and T2-weighted images (27). Immediate posttreatment MR imaging shows high signal intensity in the treated areas as well as along the intermuscular septa on T2-weighted and STIR images (Fig 11) (39). In our experience, the high signal intensity in the treated malformation persists up to 3 months after treatment, but it is no longer seen along the intermuscular septa (Fig 11) (39). At MR angiography, there is absence of enhancement in the central portion of the treated lesion with intense peripheral hyperenhancement secondary to reactive hyperemia (Fig 11) (39). This enhancement is already seen on arterial phase images (Fig 11). We found that beyond 3 months the enhancement disappears and a scar is left, which appears dark on T1-weighted images as well as on STIR images without gadolinium enhancement (Fig 12) (39). Progressive shrinkage of the lesion is often seen (39) (Figs 11, 12). In cases of extensive malformations, it can be difficult to detect the effects of treatment despite multiple treatment sessions (39). Gadoliniumenhanced imaging is therefore useful in demonstrating residual perfusion of the malformation and directing additional treatment (27). Arterial Malformations and AVMs The treatment strategy must be oriented toward achieving complete eradication of the nidus of a high-flow vascular malformation, since any incomplete treatment may stimulate more aggressive growth (15) (Fig 13). After transarterial embolization, thrombosis of the malformation is often seen (Fig 14); MR angiography may show reduced or absent shunting, with reduced or absent early opacification of the venous system. An

18 1338 September-October 2011 radiographics.rsna.org Figure 13. AVM of the knee in a 32-year-old woman who underwent two embolization procedures and two sclerotherapy sessions. (a) Arterial phase MIP image from MR angiography shows the AVM after treatment. The patient later became pregnant, and the AVM grew concomitantly. (b) MIP image from MR angiography shows the AVM 4 years later. Figure 14. Completely thrombosed pelvic AVM after transcatheter embolization in a 29-year-old woman. (a) Coronal T1-weighted image shows thrombosis of the vascular structures that composed the malformation (arrows). Coil-related metallic artifacts (arrowheads) and absence of the signal voids that represent high-flow vessels are also noted. MR angiography showed absence of abnormal arterial or venous enhancement. (b) Comparison image from pretreatment arteriography shows the vascular structures that composed the malformation (arrows). early posttreatment study should be performed, and any remaining malformation must be treated in a second stage (Fig 15). In cases where ferromagnetic coils are used for embolization, susceptibility artifacts are present (Figs 14, 15), potentially obscuring residual vascular malformation in their vicinity (39).

19 RG Volume 31 Number 5 Flors et al 1339 about the hemodynamics of vascular anomalies and thus aids in classification of the type of lesion. Furthermore, MR imaging is an excellent tool for assessment of treatment results and establishment of a long-term management strategy. Figure 15. Recurrent AVM of the right hemipelvis in a 65-year-old woman who underwent transarterial embolization. (a) Coronal T1-weighted image shows the AVM as multiple large signal voids (arrows). Arrowhead = coil-related susceptibility artifact. (b) Images from TWIST MR angiography show the hemodynamics of the AVM. Left: Branches of the hypertrophied right internal iliac artery provide inflow (arrow). Right: There is early shunting and filling of the nidus (arrowheads) and a large venous varix that drains into the right internal iliac vein (arrow) (Movie E2 [online]). Conclusions Vascular malformations are rare but important pathologic conditions because they often require aggressive treatment, and imaging plays an important role in their diagnosis. MR imaging has emerged as the preeminent imaging modality for assessment of these lesions. Contrast-enhanced MR angiography, especially dynamic timeresolved MR angiography, provides information References 1. Navarro OM, Laffan EE, Ngan BY. Pediatric softtissue tumors and pseudotumors: MR imaging features with pathologic correlation. I. Imaging approach, pseudotumors, vascular lesions, and adipocytic tumors. RadioGraphics 2009;29(3): Mulliken JB, Fishman SJ, Burrows PE. Vascular anomalies. Curr Probl Surg 2000;37(8): Hand JL, Frieden IJ. Vascular birthmarks of infancy: resolving nosologic confusion. Am J Med Genet 2002;108(4): Dubois J, Alison M. Vascular anomalies: what a radiologist needs to know. Pediatr Radiol 2010;40(6): Paltiel HJ, Burrows PE, Kozakewich HP, Zurakowski D, Mulliken JB. Soft-tissue vascular anomalies: utility of US for diagnosis. Radiology 2000;214 (3): Dubois J, Patriquin HB, Garel L, et al. Soft-tissue hemangiomas in infants and children: diagnosis using Doppler sonography. AJR Am J Roentgenol 1998;171(1): Moukaddam H, Pollak J, Haims AH. MRI characteristics and classification of peripheral vascular malformations and tumors. Skeletal Radiol 2009;38(6): Mulliken JB, Glowacki J. Hemangiomas and vascular malformations in infants and children: a classification based on endothelial characteristics. Plast Reconstr Surg 1982;69(3): Jackson IT, Carreño R, Potparic Z, Hussain K. Hemangiomas, vascular malformations, and lymphovenous malformations: classification and methods of treatment. Plast Reconstr Surg 1993;91(7): Enjolras O. Classification and management of the various superficial vascular anomalies: hemangiomas and vascular malformations. J Dermatol 1997;24 (11): Hyodoh H, Hori M, Akiba H, Tamakawa M, Hyodoh K, Hareyama M. Peripheral vascular malformations: imaging, treatment approaches, and therapeutic issues. RadioGraphics 2005;25(suppl 1): S159 S Herborn CU, Goyen M, Lauenstein TC, Debatin JF, Ruehm SG, Kröger K. Comprehensive timeresolved MRI of peripheral vascular malformations. AJR Am J Roentgenol 2003;181(3): Rak KM, Yakes WF, Ray RL, et al. MR imaging of symptomatic peripheral vascular malformations. AJR Am J Roentgenol 1992;159(1): Donnelly LF, Adams DM, Bisset GS 3rd. Vascular malformations and hemangiomas: a practical approach in a multidisciplinary clinic. AJR Am J Roentgenol 2000;174(3): Ernemann U, Kramer U, Miller S, et al. Current concepts in the classification, diagnosis and treatment of vascular anomalies. Eur J Radiol 2010;75 (1):2 11.