Contrast-enhanced magnetic resonance

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Clinical Radiology xxx (2014) e1ee10

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Contrast-enhanced magnetic resonance lymphography in the assessment of lower limb lymphoedema R.D. White a, b, J.R. Weir-McCall a, M.J. Budak a, S.A. Waugh a, D.A. Munnoch c, T.A.P. Sudarshan a, * a

Department of Clinical Radiology, Ninewells Hospital and Medical School, Ninewells Avenue, Dundee DD1 9SY, UK Department of Clinical Radiology, University Hospital of Wales, Cardiff CF14 4XW, UK c Department of Plastic Surgery, Ninewells Hospital and Medical School, Ninewells Avenue, Dundee DD1 9SY, UK b

art icl e i nformat ion Article history: Received 31 January 2014 Received in revised form 3 June 2014 Accepted 9 June 2014

Chronic lower limb lymphoedema is a debilitating condition that may occur as a primary disorder or secondary to other conditions. Satisfactory visualization of the lymphatic vessels to aid diagnosis and surgical planning has been problematic. Historically, direct lymphography was used to visualize lymphatic vessels, although the significant surgical risks involved led to this being largely abandoned as a technique. Technetium-99m lymphoscintigraphy has been the mainstay of diagnosis for over two decades, but is hampered by inherently poor temporal and spatial resolution and limited anatomical detail. Contrast-enhanced magnetic resonance lymphography (MRL) is a relatively new technique that shows early promise in the evaluation of chronic lymphoedema. This article provides the procedural technique for lower limb MRL at both 1.5 and 3 T, discusses pathophysiology and classifications of lymphoedema, provides an overview of relevant lower limb lymphatic anatomy using MRL imaging, compares the various techniques used in the diagnosis of lower limb lymphoedema, shows common pathological MRL imaging findings, and describes alternative uses of MRL. Utilization of this technique will allow more accurate diagnosis and classification of patients suffering from lymphoedema. Ó 2014 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Introduction Chronic lower limb lymphoedema is a debilitating condition, which remains both difficult to diagnose and problematic to treat, despite advances in medical science. It can

* Guarantor and correspondent: T.A.P. Sudarshan, Department of Clinical Radiology, Ninewells Hospital and Medical School, Dundee DD1 9SY, UK. Tel.: þ44 (0)1382 660111; fax: þ44 (0)1382 632128. E-mail address: [email protected] (T.A.P. Sudarshan).

occur as a primary condition or secondary to a wide range of often seemingly minor insults. Part of the cause of the slow progress in developing new options to treat this condition stems from the limited diagnostic options available to study and characterize these patients. Until recently, the only options were direct lymphography, which produces excellent anatomical detail but is invasive and has a wide range of complications, and technetium-99m lymphoscintigraphy, which provides good functional information but little anatomical detail. Both of these techniques involve ionizing radiation. Magnetic resonance lymphography (MRL) is an emerging technique that provides a non-invasive means of

http://dx.doi.org/10.1016/j.crad.2014.06.007 0009-9260/Ó 2014 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Please cite this article in press as: White RD, et al., Contrast-enhanced magnetic resonance lymphography in the assessment of lower limb lymphoedema, Clinical Radiology (2014), http://dx.doi.org/10.1016/j.crad.2014.06.007

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assessing both the anatomy and functionality of the lymphatic system without the need for ionizing radiation. This article provides the procedural technique for lower limb MRL at both 1.5 and 3 T, as used in our centre, discusses pathophysiology and classifications of lymphoedema, provides an overview of relevant lower limb lymphatic anatomy using MRL imaging, compares the various techniques used in the diagnosis of lower limb lymphoedema, shows common pathological MRL imaging findings, and describes alternative uses of MRL. Utilization of this technique will allow more accurate diagnosis and classification of patients suffering from lymphoedema.

Lymphoedema Lymphatic vessels transport around 10% of interstitial fluid to the bloodstream, with venous capillaries reabsorbing the remainder. Lymphoedema occurs when there is lymphatic drainage dysfunction but normal capillary filtration, causing excessive collection of proteinaceous fluid in the interstitium. This builds up gradually, with inflammatory change, fat hypertrophy, and fibrosis developing in the tissues. As such, the clinical manifestations of lymphoedema involve progression from soft pitting oedema to indurated, non-pitting swelling in chronic disease.1e3

Classification of lymphoedema Lymphoedema can occur due to either a congenital lymphatic disorder (primary lymphoedema),1e3 which may not manifest until adulthood, or due to an acquired abnormality (secondary lymphoedema). The latter is by far the most common.

Primary lymphoedema The type of primary lymphoedema depends on the age at which symptoms become apparent. Congenital hereditary lymphoedema (Milroy disease) is an autosomal dominant condition that presents before the age of 2 years and may resolve spontaneously. Bilateral lower limb lymphoedema usually occurs along with cholestasis and intestinal lymphangiectasia. Familial lymphoedema praecox (Meige disease) is also autosomal dominant and occurs between 2 and 35 years of age (usually during puberty), predominantly with unilateral lymphoedema. This accounts for the majority of cases of primary lymphoedema and has several associations, which include vertebral anomalies, hearing loss, and distichiasis (a double row of eyelashes). Lymphoedema tarda is the least common form of primary lymphoedema and presents after the age of 35 years.

Secondary lymphoedema1e6 Worldwide, the most common cause of secondary lymphoedema is lymphatic filariasis, in which adult Wuscheria bancrofti nematodes infiltrate and obstruct lymphatic vessels.4

In the developed world, the vast majority of cases of secondary lymphoedema are due to malignancy or its treatment (surgery or radiotherapy). Breast cancer is frequently implicated in cases of upper limb lymphoedema, with a reported incidence of up to 63% of patients following surgery.7e13 Malignant causes of secondary lymphoedema of the lower limb include gynaecological and urological malignancies.3,14 Non-neoplastic secondary causes include trauma, recurrent bacterial infection, chronic venous insufficiency, and obesity.1,3,6

Normal anatomy of the lower limb lymphatic system The lymphatic vascular network runs in parallel to the venous circulation and serves as an adjunct to the venous system for removing excess fluid, colloid, and proteins from the interstitium.3 The smallest structural lymphatic vessels are the capillaries, which are responsible for providing equilibrium of interstitial pressures through their absorptive properties. The capillaries act as contributories to the precollector vessels, which then drain to larger collector vessels, facilitating lymph drainage to regional lymph nodes and ultimately back to the venous system.1 Unlike venous and arterial circulation, the superficial-to-deep flow of lymph is not continuous and is entirely dependent on adjacent compressive forces to propel the fluid through the vessels. The external forces applied to the lymphatic vessels commonly originate from overlying surface pressures and adjacent muscular contractions from skeletal or arterial wall smooth muscle.1,3 Multiple unidirectional valves within the larger collector vessels prevent the backflow of lymph. Lymphatic drainage of the lower limb may be facilitated by either of two major pathways: the superficial or deep lymphatic networks.15

Superficial lymphatic drainage The capillaries of the superficial lymphatic network originate in the subcutaneous tissues of the lower limb and are most abundant in the feet. The large collector vessels follow three distinct pathways but ultimately converge to drain into the ipsilateral superficial inguinal nodes (Fig 1) The medial superficial lymphatic pathway parallels the great saphenous vein and arises from capillary contributories originating in the medial aspect of the foot and ankle. Larger collectors arise from the anteromedial thigh and drain into the medial superficial pathway before it terminates at the superficial inguinal nodal station.15 Lymphatic capillaries from the lateral foot and posterolateral ankle converge to become collectors that run parallel to the short saphenous vein and form the lateral superficial lymphatic pathway. The lateral superficial lymphatic pathway then bifurcates at the level at which the short saphenous vein drains into the popliteal vein. Some vessels of the lateral superficial pathway perforate the deep fascia to drain into the popliteal lymph nodes, whereas other lymphatic vessels take a superficial posterolateral course along the thigh to terminate in the superficial inguinal

Please cite this article in press as: White RD, et al., Contrast-enhanced magnetic resonance lymphography in the assessment of lower limb lymphoedema, Clinical Radiology (2014), http://dx.doi.org/10.1016/j.crad.2014.06.007

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Table 2 Modifications to imaging parameters for magnetic resonance lymphography at 1.5 T.

TR/TE (ms) a ( ) Slice thickness (mm) Number of slices iPAT FoV (mm) Matrix Voxel size (mm3) Acquisition time (s)

Coronal HASTE (all stations)

Coronal VIBE (all stations)

2000/696 e 1.5 96 e 480  360 256  256 1.9  1.9  1.5 240

3.74/1.51 25 1.5 128 2 500  375 448  448 1.1  1.5  1.5 45

HASTE, half-Fourier acquisition single-shot turbo spin-echo; VIBE, volume interpolated breath-hold examination; TR, repetition time; TE, echo time; iPAT, parallel imaging factor; FoV, field of view.

MRL

Figure 1 Coronal MIP reformats from MRL showing (a) normal lymphatic anatomy of the calf. The lateral superficial lymphatic vessel (arrow) parallels the course of the short saphenous vein (partially seen due to a small amount of venous contamination), whereas the medial superficial lymphatic vessel (arrowheads) parallels the course of the long saphenous vein. (b) Normal lymphatic anatomy of the thigh. The medial superficial lymphatic vessel (arrow heads) parallels the course of the great saphenous vein and drains into the superficial inguinal nodes (arrow). Note its slight undulating surface.

nodes along with the medial superficial lymphatic vessels.15 The collecting vessels that arise in the gluteal regions form the superficial gluteal pathways, which also drain into the superficial inguinal nodes.15

Deep lymphatic drainage Lymph from the subfascial tissues of the lower limb is drained via the deep lymphatic drainage network. The deep collector vessels run parallel to the major lower limb vasculature, namely the anterior tibial, posterior tibial, and peroneal vessels below the knee and the popliteal and femoral vessels above the knee. Nodal drainage of subfascial lymph occurs at the anterior tibial, popliteal, deep inguinal, and external iliac nodal stations.15

MR imaging allows a comprehensive evaluation of the lower limb. Standard MRI sequences provide anatomical assessment of the distribution and cause of the lower limb swelling, while contrast-enhanced MRL provides anatomical and functional information on the lymphatic drainage of the lower limb, with anatomical depiction of vessels being superior to that of lymphoscintigraphy and unenhanced MRI.16,17 Unlike lymphoscintigraphy and direct lymphography, there is no associated ionizing radiation dose.

MRL protocol In our centre, most patients are examined on a 32channel, 3 T Siemens Magnetom Trio (Erlangen, Germany). Some patients were previously imaged using a 16-channel, 1.5 T Siemens Magnetom Avanto (Erlangen, Germany). Patient preparation involves the application of topical local anaesthetic cream (mixture of lidocaine 2.5% and prilocaine 2.5%, EMLA 5%, AstraZeneca, Luton, UK) to each interdigital web space approximately 30 min prior to being scanned.

Pre-injection imaging The patient is positioned supine and imaged feet first, with spine matrix, body matrix and peripheral angiography coils in place. The patient is imaged at three “stations”: abdomen; upper legs; and lower legs. At 3 T MRL, coronal HASTE (half-Fourier acquisition single-shot turbo spin-echo)

Table 1 Imaging parameters for magnetic resonance lymphography at 3 T.

TR/TE (ms) a ( ) Slice thickness (mm) Number of sections iPAT FoV (mm) Matrix Voxel size (mm3) Acquisition time (s)

Coronal HASTE (all stations)

Coronal FLASH (abdomen)

Coronal FLASH (upper leg)

Coronal FLASH (lower leg)

2500/400 e 2 80 2 380  285 256  256 1.5  1.5  2.0 200

2.9/0.6 25 1.3 144 3 500  344 512  384 1.3  1.0  1.3 21

3.47/1.21 50 1.5 128 3 500  360 446  336 1.5  1.1  1.5 23

2.8/1.06 25 1.5 128 3 500  312 512  512 1.0  1.0  0.9 26

HASTE, half-Fourier acquisition single-shot turbo spin-echo; FLASH, fast low angle shot; TR, repetition time; TE, echo time; iPAT, parallel imaging factor; FoV, field of view.

Please cite this article in press as: White RD, et al., Contrast-enhanced magnetic resonance lymphography in the assessment of lower limb lymphoedema, Clinical Radiology (2014), http://dx.doi.org/10.1016/j.crad.2014.06.007

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Figure 2 Axial T1-weighted image showing gross oedema throughout the fat, which is hypertrophied, with thickening of the aponeuroses. In comparison, the muscle compartment returns normal signal and is of the same size as the normal contralateral limb.

T2-weighted sequences and coronal FLASH (fast low-angle shot) T1-weighted spoiled gradient-echo sequences are acquired at each station with the parameters as shown in Table 1. With 1.5 T MRL, parameters were modified as shown in Table 2; this used coronal three-dimensional (3D) VIBE (volume interpolated breath-hold examination)

T1-weighted spoiled gradient-echo sequences instead of FLASH sequences. Both sequences are 3D gradient-echo sequences; however, VIBE sequences use interpolation to acquire images faster. FLASH sequences are not interpolated in any way. On the 3 T system, it is not necessary to use an interpolated sequence to acquire comparable resolutions with low imaging times. The field of view is “skin-to-skin” wherever possible. However, this is not always possible in markedly swollen limbs, and the volume should focus on the area of interest. Volumes are not angled.

Post-injection imaging A mixture of 7.5 ml of gadolinium contrast agent (gadobutrol; Gadovist 1.0M, Bayer, Newbury, UK) and 1 ml

Figure 3 Venous thrombosis. (a) Axial T1-weighted image showing low signal in the left superficial femoral vein with subcutaneous oedema and aponeurosis thickening. The thigh muscles are also oedematous and hypertrophied compared to the other side. Compare this with the appearances in Fig 2. (b) Contrast-enhanced coronal gradient-echo image showing a thrombosed left superficial femoral vein with a filling defect throughout the visualized segment of the vessel.

Figure 4 Coronal MIP reformat from MRL showing dilatation of the medial lymphatic trunks: right 6mm, left 7mm. These stop abruptly in the mid-calf with collaterals subsequently carrying the contrast agent superiorly.

Please cite this article in press as: White RD, et al., Contrast-enhanced magnetic resonance lymphography in the assessment of lower limb lymphoedema, Clinical Radiology (2014), http://dx.doi.org/10.1016/j.crad.2014.06.007

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of 1% lidocaine is drawn up into each of two separate syringes; 1.5e2 ml of this mixture is then injected into each interdigital web space and medial to the first proximal phalanx of each foot. This needs to be an intradermal injection as subcutaneous injection will lead to poor delineation of the lymphatic vessels and extensive venous contamination. Coronal 3D FLASH (3 T MRL) or 3D VIBE (1.5 T MRL) sequences (as described in Tables 1 and 2) are re-run at 5, 15, 25, 35, 45, and (if necessary) 55 min following contrast agent injection. Pre-injection FLASH/VIBE images are used as a mask and subtracted from contrast-enhanced injection FLASH/VIBE images to highlight areas of contrast agent uptake. MIP (maximum intensity projection) images are produced by integrated scanner software. We consider imaging at 15 and 25 min to be optimal for the evaluation of the lower leg, whereas 35 and 45 min imaging is considered better for analyzing the thigh and pelvis. This technique should be adaptable for use in the evaluation of upper limb lymphoedema.

Unenhanced MRI findings Unenhanced MRI will demonstrate skin and perimuscular aponeurosis thickening with relatively preserved muscle signal and volumes (Fig 2). If there is significant swelling of the muscles, venous oedema rather than lymphoedema should be suspected18 (Fig 3). Additionally, T2 fat-saturated sequences will confidently exclude lipoedema, caused by excessive deposition of fatty tissue, by demonstrating extensive fluid stranding as the cause of the apparent fat hypertrophy.19 Unenhanced echo-train spinecho sequences can demonstrate dilated lymphatic vessels, although cannot provide the functional information that is possible with MRL.18

MRL findings MRL provides imaging of the lymphatic vessels with high spatial resolution. Lymphatic vessels often demonstrate a characteristic beading appearance with an undulating calibre throughout their length. This aids in the discrimination of dilated lymph vessels from veins. Venous contamination is occasionally a problem in MRL, particularly in the early acquisition sequences or if the injection is not truly intradermal. Careful analysis of the vessel shape and form during image interpretation can help discern venous contamination from lymphatic enhancement as veins are smooth-walled throughout, with bulging only at the location of venous valves; they also wash out on the delayed sequences.20 Pathological findings on MRL include vessel dilation, collateral formation, delayed vessel filling, delayed lymph node enhancement, honeycombing, and dermal backflow.

Figure 5 Coronal MIP reformats from two separate MRL image showing the beaded appearances of the lymphatic vessels. On the left image there is complete absence of the normal medial and lateral lymphatic trunks; this was similar on the contralateral side (not shown), consistent with a primary lymphoedema. Extensive tortuous collateral formation has formed secondary to this. Characteristic beading is best appreciated in the smaller lymphatic vessels (arrows) with this appearance becoming lost as the vessels dilate and become more ectatic. The figure on the right shows a normal medial lymphatic trunk with the slight undulations seen in lymphatic vessels.

from numerous studies by Lohrmann et al.,6,22e30 we use a cut-off of 3 mm below the knee and 5 mm or greater above the knee to be considered pathological. Lu et al.17 reported a mean diameter of pathological vessels to be 3.41  1.05 mm. However, they did not discern calf from thigh, nor dilated trunks from dilated collaterals.

Collateral formation Similar to the patterns seen in vascular obstruction, dilated collateral pathway formation is seen when there is a more proximal obstruction.22,23 These demonstrate the same beaded appearance of the main lymphatic trunks but are more numerous, smaller in calibre, and have a tortuous course (Fig 5).

Vessel dilatation

Delayed enhancement

Healthy lymphatic vessels are often well visualized but can occasionally be difficult to see at MRL,21 although dilated vessels are more readily appreciated (Fig 4). Adapted

Delayed enhancement of both the lymphatic vessels and lymph nodes occurs in lymphoedema. In a healthy lower limb, the contrast agent reaches the pelvis within 10 min,

Please cite this article in press as: White RD, et al., Contrast-enhanced magnetic resonance lymphography in the assessment of lower limb lymphoedema, Clinical Radiology (2014), http://dx.doi.org/10.1016/j.crad.2014.06.007

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Figure 6 Coronal MIP reformats from MRL in a patient with primary lymphoedema. (a) Acquisition at 10 min demonstrates normal filling of the right-sided medial and lateral lymphatic vessels, while on the left only the foot and ankle vessels (arrows) enhance. (b). Acquisition at 35 min shows the right lymphatic vessels to now be almost entirely washed out. There has been further enhancement of the left calf vessels although no well-defined medial or lateral trunk is present and this has still not extended beyond the mid-calf (arrows). Diffuse honeycombing of the left calf is also present (arrowheads).

after which the lymphatic vessels slowly wash out.20 Within the lymphatic vessels of patients with lymphoedema, peak filling typically occurs at 35e55 min, with a lower peak signal intensity23 (Fig 6). Similarly, healthy nodes are visualized at 10e20 min, whereas nodes on the affected limb show delayed enhancement, slow wash-out, and a lower peak signal intensity, when compared with the contralateral normal nodes (assuming the lymphoedema to be unilateral)20,21 (Fig 7).

Dermal backflow Dermal backflow occurs due to insufficiency and obstruction of the peripheral lymphatic system and typically starts to appear at 20 min after the subdermal injection.20 This manifests as progressive dispersion of the contrast agent into the superficial soft tissues and becomes increasingly prominent with time16,21,23 (Fig 8).

Honeycombing Honeycombing is thought to be due to enhancement of tiny interstitial lymphatic vessels or possibly contrast agent extravasation, similar to the underpinning process behind dermal backflow. This is seen as a diffuse reticular enhancement within the subcutaneous fat (Fig 9) and can also be well visualized on heavily T2-weighted sequences.17

Less common findings Lymphoceles and lymphocutaneous fistulae are less commonly observed but can be clearly demonstrated on

Figure 7 Coronal MIP reformats from MRL in a patient with left leg swelling. In (a) there is normal enhancement of the right inguinal nodes at 15 min (arrows), while no nodes are visible in the left groin. In (b), the left nodes are seen to enhance at 65 min.

Please cite this article in press as: White RD, et al., Contrast-enhanced magnetic resonance lymphography in the assessment of lower limb lymphoedema, Clinical Radiology (2014), http://dx.doi.org/10.1016/j.crad.2014.06.007

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Figure 8 Patient with primary lymphoedema. (a) On this coronal MIP reformat of the calves, a dense blush of contrast obscures the lateral lymphatic vessels in the mid-calf. (b) The axial unsubtracted images through the area of dermal backflow show the contrast to be confined primarily to the dermal tissues (arrow heads) with a dilated lymphatic running deep to this. (c) This can also be seen on the lymphoscintogram. Despite the dermal back flow, nodal enhancement is visualized at 45 min bilaterally, although the uptake on the right (arrow) is less intense than on the left (arrowhead).

MRL. Lymphoceles are readily visualized on unenhanced MRI as well-defined, thin-walled collections that return high T2 and variable T1 signal. Contrast-enhanced sequences demonstrate progressive filling over time, with dependent contrast agent layering in the lymphocele.20,25 Lymphocutaneous fistulae are identified by the presence of extracorporeal contrast agent extravasation at MRL, typically in a region of dense dermal backflow.23,29

Alternative strategies for imaging the lower limb lymphatic system Lymphoscintigraphy This is the most prevalent and frequently used technique for evaluation of the lymphatic system. A technetium-99mlabelled colloid is injected intradermally into the interdigital web spaces of both feet (in order to monitor progress and camera technique). A high-resolution gamma camera with pinhole collimator is used to acquire early (1e60 min) and late (2e24 h) phase images of the lymphatic systems.19,31 Signs of lymphoedema include poorly visualized lymphatic collectors (especially in primary lymphoedema), delayed nodal enhancement and dermal backflow31 (Fig 10). Of these features, delayed nodal enhancement is more readily identified on lymphoscintigraphy than any other technique, including MRL.16 Semi-objective quantification of lymphatic transport has been proposed using the

Transport Index Score, which is a function of the temporal and spatial location of radionuclide tracer within the lymphatic vessels and nodes.32

Direct lymphography Direct lymphography is the longest-standing method for visualization of the lymphatic system. The technique involves intradermal injection of dye into the interdigital web spaces, followed by a surgical cut-down and exposure of the dye-stained lymphatic vessels. These are then cannulated and an oil-based medium injected. A radiograph is obtained at 24 h to delineate the lymphatic vessels, with a second radiograph at 48 h to allow nodal assessment.33 This invasive technique is associated with several complications, including the risk of wound infection, pulmonary oil embolism, and lymphatic damage secondary to the injected contrast medium.34 It is also technically demanding and time-consuming. Accordingly, although it remains the reference standard for anatomical depiction of lymphatic vessels, direct lymphography fell into disuse as a diagnostic procedure following the introduction of lymphoscintigraphy, although its use in surgical planning is still reported.35

Ultrasound Ultrasound is unable to satisfactorily detect the lymphatic tree. However, it is useful for evaluating the vasculature to exclude differential diagnoses and also has

Please cite this article in press as: White RD, et al., Contrast-enhanced magnetic resonance lymphography in the assessment of lower limb lymphoedema, Clinical Radiology (2014), http://dx.doi.org/10.1016/j.crad.2014.06.007

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exclude other causes, as it is poor at visualizing the lymphatic vessels. CT signs of lymphoedema are similar to those seen at MRI, namely dermal thickening, increased volume of the subcutaneous fat with a characteristic “honeycomb” appearance, and thickened perimuscular aponeuroses. The muscle compartment should be relatively preserved, but if grossly enlarged, alternative diagnoses, such as venous obstruction, should be considered.19 Contrast-enhanced CT is also useful in evaluating the venous structures, excluding proximal nodal masses and differentiating lipoedema from lymphoedema.38

Alternative uses of MRL

Figure 9 In this patient with right leg lymphoedema, the right lateral lymphatic vessel is poorly defined while the medial vessel is mildly dilated. Throughout the soft tissues of the calf there is a diffuse “honeycomb” appearance not seen in the normal left calf. On the left the medial and lateral calf lymphatic vessels are well demonstrated. There was a previous history of right leg trauma with large calf and thigh haematoma consistent with a secondary lymphoedema.

utility in countries in which filariasis is endemic, with a characteristic “filarial dance sign” seen in dilated lymphatic ducts containing adult filarial worms.19,36,37

Computed tomography (CT) The primary role of CT in the assessment of the swollen limb is to suggest the diagnosis of lymphoedema and

MRL, with a range of different sequences and imaging parameters, has been used in the evaluation of a range of conditions other than lymphoedema. The most widespread use of MRL is for tumour staging, when evaluating lymphatic spread of malignancy. This typically uses gadolinium-based contrast agents to identify abnormal enhancement, or contrast agents with lymph node-specific uptake [e.g., superparamagnetic iron oxide (SPIO) particles], thus facilitating differentiation between nodes that appear otherwise equivocal for benignity or malignancy.39,40 It should be stressed that this type of MRL is distinct from the technique described in this paper and is primarily used to delineate nodes rather than vessels. MRL with heavily T2-weighted sequences has been shown to be effective in evaluating abdominal and retroperitoneal lymphatic vessels and depicting normal anatomy, post-surgical findings and complications as well as conditions such as intestinal lymphangiectasis, lymphatic filariasis (and other non-Wuscheria bancrofti causes of chyluria), and lymphangioleiomyomatosis.41e43 MRL has also been used to investigate postoperative lymphocele formation.30,41,44 This is a recognized complication of surgery in the inguinal or femoral regions, particularly after radical lymph node dissection,30 resulting from

Figure 10 Patient with prior radiotherapy to groin nodes. (a) Lymphoscintigraphy, with images from left to right taken at: baseline acquisition following both leg injection, 20 min, 1 h, and a magnification of the thigh at 1 h with markers at the right knee and greater trochanter. These show slow movement of the tracer bilaterally, with the tracer on the left reaching the inguinal nodes whereas the tracer on the right has diffused throughout the soft tissues with intense right ankle dermal back flow. The magnified image confirms lack of significant tracer movement beyond the level of the knee. (b) Coronal MIP reformat from MRL demonstrates tortuous collaterals around the right ankle with dermal backflow in this region. Please cite this article in press as: White RD, et al., Contrast-enhanced magnetic resonance lymphography in the assessment of lower limb lymphoedema, Clinical Radiology (2014), http://dx.doi.org/10.1016/j.crad.2014.06.007

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lymphatic vessel transection. Symptoms may develop if large or infected, and lymphoceles may require surgical treatment. MRL facilitates differentiation between lymphocele and other causes of fluid collection (e.g., postoperative seroma) by demonstrating leakage from lymphatic vessels or time-dependent enhancement of the fluid.30,44 Unenhanced variations of MRL have been used to successfully visualize the thoracic duct in normal volunteers (using electrocardiographic gating and intermittent breath holding45) and in patients with lymphoedema.46 It has also been used in the diagnosis of possible thoracic duct damage in infantile chylothorax, although problems with respiratory motion artefact have been reported due to the inability to employ a breath-holding technique in these patients.44,47 The utility of MRL in KlippeleTrenaunay syndrome (KTS) has been documented. KTS is a condition characterized by hypertrophy of soft tissue or bone, capillary malformations, and venous malformations or varicose veins, with 95% having lower limb involvement.48 The logic behind its use in KTS is to facilitate differentiation between lymphangiodysplasias and venous malformations, thus guiding management.27,47 MRL has been shown to be a useful means of delineating the extent of genital involvement in diffuse lymphangiomatosis. Diffuse lymphangiomatosis is an uncommon idiopathic condition, usually presenting before the age of 20, in which proliferation of irregular, complex lymphatic vessels occurs in multiple body systems (rarely in the genital region). Heavily T2-weighted images were considered to evaluate genital involvement more accurately than contrast-enhanced T1-weighted sequences.24 MRL has been shown to play a role in the diagnosis of other lymphatic malformations such as in Gorham syndrome.47

Conclusion Contrast-enhanced MRL combines the detailed anatomical information from traditional invasive lymphography with the functional information from lymphoscintigraphy, without the significant downfalls associated with either of these techniques. Utilization of this technique will allow more accurate diagnosis and classification of patients suffering from lymphoedema

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Please cite this article in press as: White RD, et al., Contrast-enhanced magnetic resonance lymphography in the assessment of lower limb lymphoedema, Clinical Radiology (2014), http://dx.doi.org/10.1016/j.crad.2014.06.007