State-of-the-art imaging for children with central lymphatic disorders

Dynamic contrast-enhanced MR lymphangiography (DCMRL) is a minimally invasive technique that allows for detailed imaging of lymphatic anatomy and flow dynamics. The development of intranodal DCMRL has enhanced spatial and temporal resolution by bypassing the lower extremities. DCMRL protocol comprises two phases: T2-weighted images, utilized for anatomical evaluation, and contrast-enhanced T1-weighted dynamic images, employed to assess lymphatic flow5. Patients undergo heavily T2-weighted imaging followed by time-resolved MR angiography sequences after intranodal, intrahepatic, and/or intramesenteric injection of gadolinium contrast2,4,18,19. Ultrasound-guided access to lymph nodes and visceral lymphatics is first obtained with small needles (Figure 3), and confirmed under fluoroscopy or ultrasound, before careful patient transfer to the MRI scanner2,19. At our institution, this procedure is performed in a hybrid MR-angiography suite (Figure 4), minimizing risk of dislodging the needles during transfer1. After the non-contrast T2 weighted imaging, time resolved T1 weighted imaging is performed to dynamically assess lymphatic flow after intranodal/visceral gadolinium injection. The intrahepatic dynamic magnetic resonance lymphangiography (IH-DCMRL) is an adaptation of standard DCMRL, focusing on assessing the hepatic lymphatic system. Percutaneous access to the central liver lymphatic system is achieved through adjacent lymphatic channels near branches of the portal vein. The procedure involves injecting a gadolinium-diluted contrast agent, followed by a time-resolved magnetic resonance angiography (MRA). The contrast typically flows centrally to the liver hilum, entering the cisterna chyli, and the thoracic duct flow. IH-DCMRL can aid in diagnosing chylous ascites or protein-losing enteropathy by detecting contrast leakage in the peritoneal cavity and/or the duodenum3,4. Intramesenteric dynamic contrast-enhanced magnetic resonance lymphangiography (IM-DCMRL) is employed to map lymphatic flow in patients with potential abnormal mesenteric lymphatic flow. Access to the mesenteric lymphatic system is established through a 25-gauge spinal needle placed within a lymphatic channel adjacent to the junction of an ileal or jejunal vein and the distal anterior superior mesenteric vein, or inside a mesenteric lymph node under ultrasound guidance. Similar to IH-DCMRL, IM-DCMRL involves injecting a gadolinium-diluted contrast agent, followed by a time-resolved MRA and a 3D spoiled gradient-recalled echo T1-weighted sequence with fat suppression. During IM-DCMRL, the injected contrast fans out within the mesenteric lymphatics before flowing to the cisterna chyli and the thoracic duct. Diluted gadolinium (0.1-0.2 mmol/kg) is then injected by hand at each access site and time-resolved coronal imaging performed every 30-45 seconds for 10-15 minutes to capture lymphatic flow18,19. A pre-contrast mask is acquired, then rapid 3D T1 weighted gradient echo sequences are obtained in the coronal plane every 30-45 seconds for approximately 10-15 minutes18, 19, 20. This dynamic first passage imaging shows the progression of contrast material from the injection sites into lymphatic vessels, through the cisterna chyli and thoracic duct, and ultimately drainage into the venous system. It allows for functional assessment and identification of areas of obstruction, dilation, backflow, or leakage in addition to the anatomical detail19. Despite DCMRL efficacy, there are situations where uncertainty regarding TD outlet patency persists, necessitating the use of conventional central lymphangiography (CL).

- Conventional central lymphangiography

Central lymphangiography (CL) is a fluoroscopic technique, involving the percutaneous placement of a catheter into the thoracic duct or one of its tributaries following initial lymph node access. Sequential advancement of a guidewire and microcatheter into the duct allows for contrast injection, delineating anatomy, and facilitating the injection of potential embolic agents for treatment (Figure 5). While technically challenging, CL surpasses traditional pedal lymphangiography in success rates and can be performed across all age groups19,21. This technique is considered the gold standard; however, it is time-consuming, may involve prolonged anesthesia, and entails radiation exposure. Thus, it is performed when DCMRL and other less invasive techniques are not conclusive or lymphatic embolization will be performed22.

- Contrast-Enhanced Ultrasound (CEUS)

The use of ultrasound contrast agents containing microbubbles of perfluorocarbon or nitrogen gas that enhance vascular contrast like agents used in CT and MRI has evolved in recent years23. The two main uses of CEUS in lymphatic imaging include: 1) To confirm intranodal positioning of the needle, and 2) to assess thoracic duct patency24,25. The injection of ultrasound contrast confirms needle position inside inguinal lymph nodes and provides imaging of efferent lymphatics26. Also, it is a less invasive method for evaluating thoracic duct outlet patency, whether employed independently or in combination with DCMRL25. It holds the potential to obviate the requirement for conventional lymphangiography for both purposes25,26. This technique may enable DCMRL on any MR scanner with a detachable table, which could broaden the application of this modality beyond centers with combined MR-angiography suites24,27. CEUS has also been described as a feasible technique during procedures to identify lymphatic perfusion of superficial soft tissues and to confirm lymphatic embolization27.

- CT Lymphangiography

Intranodal CT lymphangiography using water-soluble contrast is a promising alternative technique for evaluating lymphatic disorders in children, especially those with congenital heart disease. Compared to MRI lymphangiography and traditional CT lymphangiography, it offers similar spatial resolution and diagnostic quality, with wider accessibility, lower cost, less vulnerability to motion artifacts, and compatibility with medical devices28. The procedure involves ultrasound-guided access of inguinal lymph nodes, then slow injection of dilute water-soluble contrast (1 mL/kg), followed by low-dose CT imaging28. CT encounters fewer restrictions and has broader global accessibility. The application of the intranodal injection technique to CT presents an opportunity to expand the adoption of lymphatic imaging in more institutions with less technical and logistical challenges29. In recent years, a pediatric study demonstrated feasibility for identifying sites of lymphatic leakage causing post-operative chylothorax in two children, with radiation exposure comparable to routine contrast-enhanced pediatric CT28. While this technique shows significant promise, further research is warranted.

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