CHAPTER 28 Magnetic Resonance Lymphangiography

10.1055/b-0037-143484

CHAPTER 28 Magnetic Resonance Lymphangiography

Lee M. Mitsumori

KEY POINTS

Three-dimensional heavily T2-weighted sequences are performed to assess the severity, extent, and distribution of lymphedema.
The number, size, and location of individual subdermal lymphatic channels and the areas of dermal backflow can be visualized with magnetic resonance lymphangiography (MRL).
MRL can be performed on 1.5 T or 3.0 T platforms with clinically available, high-resolution, three-dimensional volumetric sequences used for MR angiography.
MRL requires the intracutaneous injection of an extracellular gadolinium-based MR contrast agent.
Image postprocessing of three-dimensional volumetric MR datasets facilitates examination interpretation.

A number of microsurgical procedures for the long-term treatment of lymphedema have been developed, and the importance of individualizing the type of operative treatment based on the degree of lymphatic dysfunction and the state of the subcutaneous tissue is being recognized. ¹ – ⁵

One of the current challenges for lymphatic surgery is that there is no standardized method of imaging the structure and function of the lymphatic circulation to evaluate the quality and severity of lymphedema. ⁶ Two lymphatic imaging methods that are clinically available are nuclear medicine lymphoscintigraphy and indocyanine green fluorescence lymphography (see Chapters 26 and 27). Although radionuclide lymphoscintigraphy has been considered the primary clinical imaging modality to diagnose lymphedema, ⁷ the limited temporal and spatial resolution of the modality does not allow the identification and localization of individual lymphatic channels. ⁸ , ⁹ Indocyanine green fluorescence lymphography is an imaging modality that is frequently used intraoperatively for microsurgical lymphatic procedures. Although indocyanine green fluorescence lymphography can provide a real-time map of the subdermal lymphatic channels, it has several disadvantages for the preoperative evaluation of lymphedema. These include a small field of view, lack of spatial information, limited skin penetration depth, ⁶ and the inability to characterize soft tissues. Thus improved lymphatic imaging techniques are needed to determine whether suitable lymphatic channels are present for reconstruction, to depict the location of suitable lymphatic channels for preoperative planning, and to delineate the status of the subcutaneous soft tissues to facilitate the selection of the optimal treatment approach.

Magnetic resonance lymphangiography (MRL) is a noninvasive technique that can image the subdermal lymphatic circulation in patients with lymphedema. MRL examinations provide the anatomic coverage to image an entire extremity with a high-resolution three-dimensional dataset and have sufficient temporal and spatial resolution to depict individual lymphatic channels and areas of dermal backflow. Imaging capabilities that are needed for the preoperative planning of lymphatic microsurgery. ⁴ , ⁹ In addition, other MR pulse sequences can be included in the examination to evaluate the status of the subcutaneous soft tissues. ⁸ With current 1.5 T and 3.0 T MR platforms, imaging data are acquired as three-dimensional volumetric datasets, which is important to enable the use of widely available image postprocessing algorithms that facilitate examination interpretation and microsurgical treatment planning. ⁹ , ¹⁰

The main difference between MRL and other conventional contrast-enhanced MR examinations is the route of contrast administration. In MRL, a small volume of an extracellular gadolinium-based MR contrast agent is injected intracutaneously in the interdigital webspaces of the hand or foot to promote contrast uptake by the lymphatic circulation. The low molecular weight of the extracellular MR contrast agents allows the lymphatic circulation to absorb the contrast agent in the interstitial space. ¹¹ Because of the off-label route of administration, the safety of the intracutaneous administration of extracellular gadolinium-based MR contrast agents was initially evaluated with animal experiments. ¹² Since the first few human clinical studies, ¹³ , ¹⁴ several studies have been published that support the safety of the intracutaneous administration of different extracellular gadolinium-based MR contrast agents for MRL (gadopentetate dimeglumine, ⁹ gadoterate meglumine, ¹³ gadoteridol, ⁴ , ¹⁵ gadodiamide, ¹⁴ , ¹⁶ and gadobenate dimeglumine ¹⁷ , ¹⁸ ). Although the intracutaneous contrast injection has been described as well tolerated by patients and no complications were reported by these studies, patients do describe mild to moderate pain during the injection, and some have transient swelling of the dorsum of the extremity around the injection site. ¹¹ , ¹³ , ¹⁴ , ¹⁶ To reduce the pain of the injection, a local anesthetic can be mixed with the contrast agent before intracutaneous administration, and a small-gauge needle should be used. ¹¹

MRL Imaging

An MRL examination consists of two main components: a T2-weighted sequence to depict the severity and distribution of lymphedema and a fat-suppressed three-dimensional spoiled gradient recalled–echo (3D-SPGR) sequence after the intracutaneous injection of MR contrast to image lymphatic channels. Because the intracutaneously administered contrast agent is also absorbed by the venous circulation, ¹ , ⁹ , ¹¹ the same high-resolution 3D-SPGR sequence can be repeated after a separate intravenous injection of contrast to obtain an MR venogram. ¹⁹ Having the delayed MR venogram to compare with the MRL can be helpful to differentiate enhancing lymphatic channels from contrast-containing veins.

MRL can be performed at 1.5 T or 3.0 T. ⁹ , ¹⁵ – ¹⁷ Patient positioning, coil placement, and scan orientation will depend on whether the examination is of an upper or lower extremity and whether unilateral or bilateral imaging is performed. For unilateral imaging of the upper extremity, the patient is positioned supine and head first in the scanner gantry. The arm that will be scanned is placed at the patient’s side, and the patient is positioned as far laterally as possible with the arm propped with a pad to the level of the magnet isocenter. Surface coils are then positioned to image the target arm from the midhand to the shoulder. At 1.5 T we use a 16-channel torso phased array surface coil, whereas at 3.0 T a digital system with imbedded table coil elements is used, which allows coverage of the entire extremity with automatic coil element selection for each individual scan location. Headfirst patient positioning is helpful to allow access to the patient’s hand for the intracutaneous contrast injection that is performed midway through the examination.

For the lower extremities, MRL is performed either as a unilateral or bilateral examination, depending on the clinical request. Patients are placed supine and feet first on the scanner table to allow access to the patient’s feet from the far side of the gantry for the intracutaneous contrast injection. At 1.5 T a 16-channel torso phased array surface coil is used, and a two-station examination is performed. ¹⁶ The surface coil is initially positioned to cover the lower legs from the midfoot to above the knees and then repositioned to cover the thighs from the knees to the groin.

Alternatively, a dedicated peripheral vascular surface coil can be used to image the upper and lower legs simultaneously. ¹⁴ At 3.0 T we use a digital system that allows automatic coil element selection for the desired scan range, and the study is performed as a three-station examination. Because inhomogeneous fat suppression can produce regions of high signal that can obscure lymphatic channels and areas of dermal backflow ⁹ (Fig. 28-1), patient position with unilateral examinations is offset laterally to place the extremity of interest as close as possible to the magnet isocenter, which improves shimming and the uniformity of fat suppression.

**FIG. 28-1** This 60-year-old woman had a left mastectomy for breast cancer and presented with progressive left arm swelling. A and B, Coronal full-volume maximum intensity projection (MIP) and single-plane multiplanar reformation (MPR) reconstructed images of the left arm from the T2-weighted sequence demonstrate moderate epifascial edema in the lateral upper arm *(arrow)*. C and D, Coronal full-volume MIP and single-plane MPR reconstructed images of the contrast-enhanced MRL depict areas of skin enhancement representing dermal backflow in the proximal, mid, and distal left arm *(arrowheads)*. In C the scalloped areas of high signal on MRL (*) represent regions of inhomogeneous fat suppression. Full-volume MIP reconstructions are helpful to depict the extent and spatial distribution of the findings, whereas single-plane MPR images are used to define the location of a finding and exclude artifacts. Interactive examination review with image postprocessing software allows co-localization of a finding on different sequences and the creation of different viewing planes. E, Reconstructed axial MPR image from the MRL scan data made through the distal area of dermal backflow *(arrowhead)* seen on the full-volume MIP. The axial MPR confirms that this reflects skin enhancement (DBF3), which is located along the posterior medial surface of the arm. The patient was considered a candidate for lymphaticovenular bypass.

Two primary sequences are included in our MRL examination: (1) a heavily T2-weighted three-dimensional turbo spin-echo with spectral fat suppression (spectral presaturation with inversion recovery) to define the severity and extent of edema and (2) a dynamic T1-weighted three-dimensional spoiled gradient–recalled echo (3D T1w GRE) with fat suppression before and after the intracutaneous contrast injection to visualize enhancing lymphatic channels and dermal backflow (Figs. 28-1 and 28-2). Example MR sequence parameters used at our institution are presented in Table 28-1.

**FIG. 28-2** This 72-year-old woman had a left mastectomy with axillary lymph node dissection and radiotherapy. She presented with progressive left arm swelling. A, Coronal full-volume MIP reconstruction of the T2 sequence of the left arm reveals diffuse high signal intensity throughout the arm, reflecting severe lymphedema. B, Corresponding axial MPR reconstructed T2 image of the distal forearm shows the circumferential distribution and severity of the edema. C and D, Coronal full-volume MIP images of the left arm before and 30 minutes after intracutaneous contrast injection in the hand. The MRL shows multiple enhancing irregular lymphatic channels throughout the arm. The patient was considered a candidate for lymphaticovenular bypass.

**TABLE 28-1 Example Sequence Parameters of MRL**
	T2w 3D TSE	3D T1w GRE (1.5 T)	3D T1w GRE (3.0 T)
Sequence	3D Multishot TSE	3D T1-TFE	3D T1-FFE
Orientation	Sagittal	Sagittal	Sagittal
Profile order	Reverse linear	Low-high radial	Linear
Half-scan factor	0.8		0.85 × 0.85
Fat suppression	SPIR	SPIR	Dual-echo Dixon
Field of view	380 × 312 × 150 mm ³	485 × 162 × 100 mm ³	360 × 221 × 147 mm ³
Voxel size	1.7 × 1.7 × 3.0 mm ³	1.3 × 1.3 × 1.0 mm ³	1.2 × 1.2 × 1.6 mm ³
TR	2500 ms	7.2 ms	6.2 ms
TE	350 ms	3.3 ms	1.5 ms/2.8 ms
Flip angle	90 degrees	30 degrees	20 degrees
SENSE factor	2 in AP direction	None	None
Scan time	3:47 per station	1:27 per dynamic	1:25 per dynamic
These sequence parameters reflect typical values for the scanner platform used at our institution. 3D, Three-dimensional; FFE, fast field echo; SENSE, Sensitivity encoding; SPIR, spectral presaturation with inversion recovery; T2w, T2-weighted; TE, echo time; TFE, turbo field echo; TR, repetition time; TSE, turbo spin-echo.

Currently we perform seven dynamic phase acquisitions at approximately 5-minute intervals (0, 5, 10, 15, 20, 25, and 30 minutes). ¹⁷ After these initial dynamic phases are acquired, the images are reviewed to determine if additional phases are needed to include the entire extent of lymphatic enhancement. After the MRL, we perform an MR venogram to help differentiate subdermal lymphatics from veins. For the MR venogram, a single phase of the 3D T1w GRE scan used for the MRL is repeated 120 to 180 seconds after an intravenous injection of MR contrast. The three-dimensional scans of the upper or unilateral lower extremities are performed in the sagittal orientation for more efficient scanning. The three-dimensional scans of the bilateral lower extremities are performed in the coronal orientation for the larger lateral scan coverage needed to include both lower extremities in the same scan field of view. Currently at our institution, the average examination time for an upper or lower extremity MRL is between 1.5 and 2 hours.

The same contrast injection protocol is used at both field strengths. The intracutaneous injection of MR contrast consists of a mixture of 10 ml of contrast (gadobenate dimeglumine) with 1 ml of 1% lidocaine and 1 ml of sodium bicarbonate. ¹⁷ The contrast-anesthetic mixture is then drawn into a 5 ml syringe for a unilateral examination or a 10 ml syringe for a bilateral examination. The skin of the dorsal hand or foot is sterilely prepared, and 1 ml of the contrast-anesthetic mixture is injected intracutaneously into each of the four interdigital webspaces of the hand or foot with a 26-gauge needle (total 4 ml per extremity). After the intracutaneous contrast has been administered, the injection sites are massaged for 60 seconds to promote lymphatic uptake. ⁷ , ¹⁶ The intravenous contrast administration for the MR venogram can be performed manually or with a power injector typically in an antecubital vein and is composed of 0.1 mmol/kg of contrast (gadobenate dimeglumine) injected at a rate of 1.0 ml/sec followed by a 20 ml saline flush at the same rate. Although several different gadolinium-based MR contrast agents have been used for MRL, ⁴ , ⁹ , ¹³ , ¹⁶ , ¹⁷ we elected to use gadobenate because of the higher relaxivity, thermal stability, and potential for protein binding that this contrast agent provides. ²⁰ , ²¹