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ECR 2019 / C-2107
Certificate of Merit
Ultrasmall Superparamagnetic Iron Oxide Enhanced Peripheral MR Lymphangiography – An Effective Method to Reduce Venous Contrast Contamination through Selective Blood Pool Suppression
Congress: ECR 2019
Poster No.: C-2107
Type: Educational Exhibit
Keywords: Oedema, Imaging sequences, Contrast agent-intravenous, MR-Angiography, MR, Lymphography, Veins / Vena cava, Contrast agents, Cardiovascular system
Authors: O. Kolokythas1, N. Briller1, J. Revels1, S. Kim2, P. Neligan1, L. Mitsumori3, A. Gutzeit4, N. Lalwani5, J. H. Maki6; 1Seattle, WA/US, 2New York, NY/US, 3Honolulu, HI/US, 4Luzern/CH, 5Winston Salem, NC/US, 6Denver, CO/US
DOI:10.26044/ecr2019/C-2107

Background

Lymphatic Channels – Function and Anatomy

  • Responsible for drainage of fluid (lymph) from the interstitial space
  • Begin as blind ending interstitial sinuses that progressively coalesce into larger channels that flow to lymph nodes and then to larger ductal systems including the cisterna chyli and thoracic duct
  • Peripheral lymphatic channels are much more present in the subcutaneous tissues than in muscles and deep tissues.
  • Lymphatic channels describe a slightly spiral course toward proximally (Fig. 1)
  • Lymphatic channels have a slightly irregular caliber and beaded or discontinued appearance

 

Important diagnostic clues to distinguish veins from lymphatics:

  • Deep veins occur paired
  • Normal veins are smooth and straight, with valves
  • Varicose veins can be tortuous and variable in caliber mimicking a beaded appearance! 

Morphologic challenges:

  • Similarity of subcutaneous veins and lymphatics - both can have a spiral course (Fig. 1 and Fig. 10):
Fig. 1: Comparison of spiral course of superficial veins of a left upper extremity (left) due to venous concomitant enhancement after distal intradermal gadolinium injection and spiral course of abnormally visible lymphatic channels of a left lower extremity (right) due to lymphatic obstruction in two patients. Both veins and lymphatic channels have a similar course. However lymphatic channels differ from veins mainly based on their beaded and irregular morphology compared to the smooth appearing veins (multistation MIPs reconstructed from mDixon T1 weighted spoiled gradient echo sequences).
References: Department of Radiology, University of Washington, University of Washington Medical Center - Seattle/US

 

  • Obstructed dilated lymphatic channels can mimick varicose veins (Fig. 2):
Fig. 2: Varicose appearance of a dominant dilated obstructed lymphatic channel medially in the left lower extremity, mimicking varicosis of the saphenous vein. Origin at the mid dorsum of the foot identifies this vessel as a lymphatic channel and not as the saphenous vein. Multistation MIP reconstructed from mDixon T1 weighted spoiled GRE after intradermal injection of a total of 2.5cc gadobenate dimeglumine mixed with 2.5cc lidocaine 1% into the interdigital web spaces.
References: Department of Radiology, University of Washington, University of Washington Medical Center - Seattle/US

 

 

Pathophysiology of Lymphoedema

  • Swelling of an extremity due to retention of lymphatic fluid
  • Retention of lymphatic fluid is due to interruption of lymphatic channels
  • Chronic retention of interstitial fluid can result in fat deposition (lipoedema) cutaneous weeping (lymphorrhea) and dermal fibrosis

 

Risk Factors for Lymphoedema

  • Age
  • Obesity
  • Inflammatory conditions (rheumatoid or psoriatic arthritis) 

 

Etiologies of Lymphoedema

 

Primary Lymphoedema

  • Congenital lymphoedema
  • Lymphoedema praecox
  • Lymphoedema tarda

 

Secondary Lymphoedema

  • Surgery
  • Radiation
  • Infection
  • Malignancies
  • Trauma

 

Primary Lymphoedema (failure of proper development of lymphatic channels)

  

- Type I: Familial congenital lymphoedema (Fig. 3)

  • VEGF receptor 3 mutation
  • Begins in infancy
  • Abnormal lymph node formation
Fig. 3: Primary Type I (Nonne-Milroy) lymphoedema of the left lower extremity.
References: Department of Radiology, University of Washington, University of Washington Medical Center - Seattle/US

 

- Type II:

  • Lymphoedema praecox
  • Adolescence and puberty (Fig. 4)
Fig. 4: Severe primary type II lymphoedema of both lower extremities with dermal fibrosis and ulcerations of the left calf.
References: Department of Radiology, University of Washington, University of Washington Medical Center - Seattle/US

 

- Lymphoedema tarda: 

  • Late onset after 35 years of age
  • Very rare

 

 

Secondary Lymphoedema (damage to lymphatic channels)

  • More common than primary lymphoedema
  • Filariasis is the #1etiology of lymphoedema worldwide (Fig. 5)
Fig. 5: Massive secondary lymphoedema of the right lower extremity due to filiariasis ("elephantiasis").
References: Department of Radiology, University of Washington, University of Washington Medical Center - Seattle/US

 

  • Malignancies and treatment complications of malignancies are the #1 cause of lymphedema in the western world, mostly breast cancer and gynecologic tumors (Fig. 6).
Fig. 6: Secondary lymphoedema of the left upper extremity following left axillary lymph node dissection and partial left mestectomy for breast cancer.
References: Department of Radiology, University of Washington, University of Washington Medical Center - Seattle/US

 

 

Clinical Presentation and Workup of Lymphoedema

  • Clinical history – attempt to determine primary or secondary lymphoedema
  • Symmetric or asymmetric swelling of one of bilateral upper or lower extremities
  • Extraordinary lymphoedema can present with dermal thickening, discoloration, cutaneous weeping (lymphorrhea), reduced mobility, pain, skin breakdown, and ulcerations (Fig. 4)
  • Often clinically difficult to differentiate lymphoedema from venous insufficiency: both lymphoedema and venous insufficiency present with extremity pitting oedema
  • Venous insufficiency can lead to lymphoedema (phlebolymphoedema)
  • Patients may be misdiagnosed as venous insufficiency, which does not improve with medical management
  • Use of diuretics for venous insufficiency can worsen lymphoedema

 

 

Treatment Options for Lymphoedema

  • Mostly conservative physiotherapy
  • Microsurgical techniques:
  1. Lymphaticovenous anastomosis (LVA)
  2. Vascularized lymph node transfer (VLNT) 

Both microsurgical techniques require imaging mapping of oedema and detailed venous and lymphatic mapping to

  • identify distinct veins
  • identify distinct lymphatic channels suitable for LVA planning
  • identify areas of dermal backflow to assess locations of lymphatic obstruction and aid in the decision making for surgical techniques

 

 

Imaging Methods for Detection of Lymphoedema, Venous, and  Lymphatic Channels

  • Lymphoscintigraphy (historically done, low spatial resolution, ionizing radiation)
  • Fluorescent (Indocyanine green) lymphangiography (used pre- and intraoperatively) Fig. 7
  • Conventional lymphangiography (rarely done nowadays due to the high rate of hypersensitivity reactions, ionizing radiation)
  • MR lymphangiography (MRL), MR venography (MRV) 

 

Fig. 7: Fluorescent lymphangiography through interdigital intradermal injections of a total of 5mL indocyanine green demonstrates distinct subcutaneous lymphatic channels at the dorsum of the left hand which extent to areas of extensive dermal backflow (small reticular fluorenscent vessels) in the forearm, indicating the location of lymphatic obstruction.
References: Department of Radiology, University of Washington, University of Washington Medical Center - Seattle/US

 

 

MR Lymphangiography

  • MR lymphangiography has largely replaced conventional lymphography due to its better tolerability and its ability to demonstrate the spatial relationship between the lymphatic and vascular system for surgical planning.
  • Conventional MRL with a dual injection scheme of dermal injection for lymphatics followed by intravenous injection for venous mapping at the end of the exam suffers not infrequently from venous contrast contamination of lymphatic maps, decreasing its specificity and jeopardizing the accuracy of the method.

 

 

Conventional MR Lymphangiography

 

Conventional MR Lymphangiography - Interstitial Injection Technique

  • Thorough disinfection of skin over distal hand/foot 
  • Injection of 5mL solution of 1:1 Gd/lidocaine 1% per extremity
  • Inject 1mL between 1st through 4th web spaces of fingers/toes (Fig. 8)
  • Web space medial to thumb/great toe receives 2mL dose (Fig. 9)
  • Elevation and gentle massaging of injected extremity upstream for 1 minute from distally (hand/foot) to proximally (to above elbow/knee). 

The purpose of the massage is to promote migration of contrast within the lymphatics centrally.

 

Fig. 8: 1mL of a 1:1 solution of 1% lidocaine and gadolinium is being injected intradermally into the each of the interdigital web spaces 2-4. Here the 4th web is being injected.
References: Department of Radiology, University of Washington, University of Washington Medical Center - Seattle/US

 

Fig. 9: 2mL of the same 1:1 solution of 1% lidocaine and gadolinium is being injected intradermally into the first interdigital web.
References: Department of Radiology, University of Washington, University of Washington Medical Center - Seattle/US

 

 

Conventional MR Lymphangiography - Imaging Technique 

 

The 4 basic imaging components are the same for the conventional and the blood pool suppressed MRL (well described in Mitsumori et al. J MagnResonImaging 2015):

  1. Edema sequence: 3D T2-FS 
  2. MRL: 3D-spoiled GRE T1 before and after interstitial Gd injection. Usually two distinct time points of T1w 3D-GRE, one 20min and one 45-50min after intradermal injection, are sufficient to depict lymphatic channels in the distal and proximal extremity. Additional time points may be acquired, if pathologic lymphatic vessels or a lymphatic leak are expected more proximally
  3. combined MRV/MRL: 3D-spoiled GRE T1 using intravenous Gd injection after MRL
  4. Staged axial circumference measurements or volumetric calculation of extremities
  • Components 1-3 are reconstructed into 3D MIP and axial or multiplanar reconstructions
  • Component 4 is being measured on distinct axial single shot T2w images or reconstructed based on 3D-GRE T1weighted sequences into 3D volume rendered images 

 

 

Advantages of conventional MR Lymphangiography:

  • Only one contrast agent (gadolinium) is being used (even though two routes of administration are needed)
  • Robust enhancement of MRL
  • Robust enhancement of MRV

 

Disadvantage of conventional MR Lymphangiography:

  • Concomitant gadolinium enhancement of veins after intradermal injection can make the distinction of lymphatic channels from veins difficultVenous contamination occurs with subcutaneous, but also with careful intradermal injection technique (Fig. 10)
  • Workflow of acquisitions is interrupted by intravenous injection for MRV
Fig. 10: Concommittant venous enhancement of superficial veins of the left forearm on conventional MR lymphangiography: Left figure: Abnormally dilated and enhancing lymphatic channels at the dorsum of the hand crossing the wrist (arrows) surrounded by dermal backflow (arrowheads). Undesired is the enhancement of surrounding veins (curved arrows) after interstitial gadolinium injection into the interdigital web spaces, which may decrease the accuracy of the interpretation of the lymphatic abnormalities fur surgical planning. Right figure: conventional MR venogram after intravascular injection of gadolinium confirms that the previously enhancing vessels are veins and not lymphatic vessels (multistation MIPs reconstructed from high resolution mDixon T1 weighted spoiled gradient echo sequences after intradermal injection of 2.5cc gadobenate dimeglumine mixed with 2.5cc lidocaine 1%).
References: Department of Radiology, University of Washington, University of Washington Medical Center - Seattle/US

 

 

MR Lymphangiography - Imaging Findings

 

Normal MR Lymphangiogram:

  • Interstitial contrast pooling at injection site including dorsum of the hand/foot
  • No lymphatic channels visible
  • Lymph nodes can be present and enhance with intralymphatic gadolinium 

 

Lymphatic disruption/blockage on MRL:

  • Pathognomonic: reticular channels and ground glass in subcutaneous tissues on T1w gadolinium with corresponding interstitial fluid on T2 ("dermal backflow"):  Fig. 1, Fig. 2Fig. 10Fig. 12
  • Presence of distinct lymphatic channels, which are not seen normally (Fig. 1Fig. 2Fig. 10Fig. 13)

 

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