Method of dynamic 3D visualization of lymphatic system

Abstract

FIELD: interventional radiology.SUBSTANCE: can be used for dynamic 3D visualization of the lymphatic system using flat-detector computed tomography (FD-CT). A bilateral puncture of the inguinal lymph nodes is performed under ultrasound control, followed by the simultaneous introduction of a water-soluble radiocontrast agent into the inguinal lymph nodes on both sides. After the start of contrast administration, continuous fluoroscopy or digital subtraction angiography is performed, confirming the flow of contrast from the lymph node into the draining lymphatic ducts and excluding its extravasation beyond the capsule. The first FD-CT scan of the area of interest is performed before the contrast begins to flow through the lymphatic system. Next, under the control of intermittent fluoroscopy, the dynamic flow of contrast through the lymphatic system is monitored. Upon reaching the area of interest, repeated series of FD-CT scans are performed, native, post-contrast multiplanar reconstructions and dynamic 3D models of the angiographic complex of the lymphatic bed are obtained in a single stereotactic space.EFFECT: method improves the accuracy, safety, and speed of 3D visualization of the lymphatic system with reduced radiation exposure and without the risk of extravasation by combining precise bilateral ultrasound-guided puncture of the inguinal lymph nodes, precisely dosed simultaneous administration of a water-soluble contrast agent at a constant rate, and dynamic monitoring of its progress using intermittent fluoroscopy; this allows for native and repeated FD-CT scanning to be performed precisely in the target phases for subsequent multiplanar reconstruction in a single stereotactic space.1 cl, 8 dwg, 1 ex

Description

[0001] The invention relates to medicine, namely to interventional radiology, and can be used for dynamic 3D visualization of the lymphatic system to improve the results of diagnostics and X-ray surgical treatment of various diseases of the lymphatic system and diseases associated with the lymphatic system.

[0002] The lymphatic system has long remained a poorly understood area of ​​clinical angiology and a difficult area to visualize in the context of radiological diagnostics. Unlike the arterial and venous systems, the lymphatic vessels have a more complex anatomical architecture, thin vessel walls, lack of pulsation, slow and irregular fluid flow, and an extremely high level of individual anatomical variation.

[0003] Nevertheless, interest in the lymphatic system has grown with the evolution of various fields in radiodiagnostics, particularly in the context of pathologies such as postoperative chylothorax, chylous ascites, lymphocele, plastic bronchitis, protein-losing enteropathy, portal hypertension, chyluria, inguinal lymphedema, and a host of other congenital and acquired lymphatic and lymphatic-related diseases. With the development of interventional radiology, it has become possible not only to visualize lymphatic anatomy but also to specifically intervene in pathological aspects of lymphatic circulation.

[0004] One of the first steps toward radiological visualization of the lymphatic bed was the introduction of pedal lymphangiography, first described by Kinmonth in 1951 and improved by Wallace in 1961. The method involved injecting iodine-containing oil, lipiodol, into the lymphatic vessels of the dorsum of the foot, which allowed radiographic visualization of not only the lymph nodes and lymphatic vessels of the extremities, but also various parts of the central lymphatic system (CLS), including the lumbar lymphatic trunks, the cisterna chyli, and the thoracic duct (TD). Pedal lymphangiography quickly took a leading place in the diagnosis of lymphomas, especially in staging the disease, and for more than half a century remained the only method for displaying lymphatic anatomy in vivo [1].

[0005] However, as clinical experience accumulated, serious shortcomings of the method became apparent. It required tissue dissection, labor-intensive identification, and catheterization of small vessels, was extremely sensitive to technique, and was associated with a number of serious complications. Reports of fat embolism, impaired pulmonary perfusion, and even fatal outcomes associated with the administration of large doses of lipiodol had already been published by the 1960s. Thus, despite its high visualization value, the method proved unsuitable for widespread clinical use and was gradually replaced by less traumatic approaches [2].

[0006] A key technological breakthrough occurred in 1995, when Sore first performed percutaneous transabdominal catheterization of the thoracic duct dilatation under fluoroscopic guidance. This set a precedent for the transition from purely diagnostic procedures to interventional ones. As early as 1998, the first cases of successful thoracic duct embolization in post-traumatic chylothorax were described. Thus, lymphangiography ceased to be merely an imaging tool; it became a therapeutic tool [3, 4].

[0007] However, the technical complexity of the transabdominal approach, the need for lengthy fluoroscopy, the risk of damage to paraorganic structures, and the difficulty of navigation have limited the widespread adoption of these techniques [5]. A need has arisen for a simpler, safer, and more universal method of accessing central lymphatic structures.

[0008] The concept of therapeutic lymphangiography emerged in 2009–2011 in response to this challenge. Japanese clinicians demonstrated that intra-lymph node administration of lipiodol could, by itself, lead to closure of fistulas and leaks through the mechanism of sterile lipogranulomatous inflammation. This discovery transformed the diagnostic approach: the pedal lymphangiography procedure itself acquired therapeutic potential [6, 7, 8].

[0009] Around the same time, the technique of intranodal lymphangiography (IL) was developed, first described by Rajebi et al. in 2011. This technique involved ultrasound-guided puncture of the inguinal lymph node, followed by the administration of an oil-based radiocontrast agent (Lipiodol). The method proved to be simple to implement, did not require surgical access, and could be used in critically ill patients, including those in intensive care and pediatric patients. Just one year later, studies by Nadolski's group confirmed that intranodal lymphangiography not only visualizes the thoracic duct in 80-90% of cases but also leads to spontaneous closure of lymph leaks in a significant proportion of patients [9, 10].

[0010] The next logical step was to expand the diagnostic capabilities of magnetic resonance imaging. In 2014, Dori introduced dynamic contrast-enhanced MRI lymphangiography (DCE-MRI), in which diluted gadolinium was injected into the inguinal lymph node, and a series of images were acquired at a rate of up to one frame per second. This approach enabled the first dynamic 3D visualization of lymph flow through the lymphatic vessels, assessing recirculation, retrograde flow, stasis, and even the smallest fistulas.

[0011] The primary and often insurmountable drawback to the widespread use of this technology is the requirement for a hybrid X-ray surgical operating room equipped with an angiographic complex and an MRI machine of at least 1.5 Tesla, all sharing a single angiographic table. Therefore, this technique is still used only in a small number of highly specialized centers [11, 12].

[0012] Later, dynamic MSCT lymphangiography technology using a water-soluble radiocontrast agent was proposed, but it too was not widely adopted. This is also due to the fact that planar fluoroscopy, which is inaccessible to MSCT, remains necessary to confirm reliable catheterization of the inguinal lymph nodes and monitor the progress of the radiocontrast agent through the lymphatic system [4, 12].

[0013] Thus, none of the above methods, taken individually, provided a universal solution. Intranodal oil lymphangiography provided anatomical visualization and local therapy, but did not allow for dynamic 3D imaging, and was sometimes associated with pulmonary embolism and cerebral artery embolization. MRI lymphangiography and MSCT lymphangiography provide three-dimensional functional information, but are difficult to access in practice, cannot be performed in most medical institutions, and, furthermore, do not allow for simultaneous treatment of identified diseases [2, 11]. Transabdominal approaches were highly effective, but required expertise and were time-consuming. There was a need to integrate all of these components into a single, logically complete clinical protocol.

[0014] This capability was made possible by modern angiographic systems with flat-detector computed tomography (PDCT). With their development, it became possible to perform high-precision 3D scanning of the lymphatic system immediately after intranodal injection of oil contrast, without changing the patient's position. This shortened the procedure time, reduced the dose of oil contrast agent, and eliminated the need to move the patient between machines. PDCT navigation has become the basis for targeted embolization, stent placement, balloon angioplasty, and other interventional procedures directly based on imaging results.However, the use of oil-based radiocontrast agents still takes a long time and does not allow for the visualization of retrograde lymph flow through small lymphatic ducts (due to high viscosity), and can also lead to complications in the form of pulmonary and cerebral embolism (in the case of using large volumes of contrast agents, as well as in cases of heart defects with right-to-left shunting).

[0015] A retrospective analysis shows that each lymphangiographic method has proven to be limited in its capabilities, whether due to technical complexity, invasiveness, incomplete visualization, or the impossibility of immediate intervention. Classical pedal lymphangiography, despite its informative value, has long since lost its clinical applicability due to severe side effects. Thoracic duct catheterization requires specialized training and is available only in highly specialized centers. Dynamic MRI-LAG, in turn, provides exclusively functional information, but requires a hybrid X-ray room, a separate MRI session, and cannot be used in urgent interventions in the vast majority of medical institutions.

[0016] Even modern isolated methods—such as intranodal LAG using Lipiodol or PDCT-LAG using Lipiodol—while offering diagnostic value, do not provide a complete picture. This is due to the high viscosity of Lipiodol and its inability to penetrate very thin lymphatic vessels (e.g., to visualize retrograde lymphatic flow in the lungs) or very small lymph leaks (e.g., to diagnose lymphorrhea after bowel surgery). Thus, intranodal LAG using Lipiodol is limited in visualization depth and cannot reflect the dynamics of lymph flow, while PDCT, in turn, does not assess the functional state of the vessels. Finally, none of the above methods, taken individually, allows for the diagnosis, navigation, and immediate treatment of pathology within a single approach and a single session.

[0017] Summarizing the evolution and analysis of existing lymphatic system imaging methods, the need for a new, more universal, technically reproducible, and clinically effective approach becomes clear. Modern practice demands that diagnostic and interventional techniques not only be anatomically accurate but also highly safe and adaptable to specific clinical needs, minimize the invasiveness of the procedure, and eliminate the need for multiple stages associated with the risk of repeated patient transfers and complicated procedural logistics. It is within this paradigm that the concept of the proposed method, combining ultrasound navigation and PDCT lymphangiography using a water-soluble radiocontrast agent, was developed.

[0018] Ultrasound imaging, as the most accessible, safe, and mobile technology, enables rapid identification of peripheral lymph nodes, primarily the inguinal ones, as the main entry point into the lymphatic system. The ability to precisely position a needle under constant visual control, in real time, and without the use of ionizing radiation, makes ultrasound an ideal first step in a combined protocol. It eliminates the need for surgical access, reduces procedure start time, and can be used even in unstable patients. Importantly, ultrasound can be used without any restrictions in any radiology room, including with a PDCT angiograph.

[0019] However, after successful intranodal puncture and contrast agent administration, a high-precision three-dimensional reconstruction of the lymphatic system becomes necessary for subsequent intervention. This is where ultrasound encounters a fundamental limitation: its inability to adequately depict mediastinal and para-aortic lymphatic structures, especially near the diaphragm and in the presence of gas interposition, bone artifacts, or postoperative changes.

[0020] At this stage, it is most rational and effective to utilize the capabilities of a hybrid angiographic system with intermittent fluoroscopy, digital subtraction angiography (DSA), and PDCT. PDCT allows for instant three-dimensional submillimeter images of the lymphatic vessel anatomy, while DSA allows for visualization of the contrast medium flow from the peripheral lymph node to the central collecting vessels. This spatial accuracy is complemented by the advantage of the angiographic format, which allows the physician to immediately perform therapeutic interventions, such as targeted embolization, sclerotherapy, coagulation, or stent graft placement, without changing the surgical field or transferring the patient.

[0021] The combination of ultrasound and PDCT navigation allows for a logical separation of the intervention stages: fast, safe, and precise entry into the lymphatic system using ultrasound and detailed anatomical navigation using PDCT.

[0022] Thus, the development of a new method based on the sequential application of ultrasound navigation and intranodal lymphangiography using a water-soluble radiocontrast agent and an angiographic system equipped with PDCT reflects modern requirements for the safety, reproducibility, efficiency, and functional completeness of interventional procedures on the lymphatic system. This allows the diagnosis and treatment of lymphatic pathologies to be transformed from disparate, step-by-step processes into a single, standardized, and technically manageable procedure, thereby significantly improving interventional safety and patient prognosis, reducing hospital stay, and expanding the capabilities of modern radiology.

[0023] The technical result of the invention is fast, safe and accurate entry into the lymphatic system and detailed anatomical navigation, the possibility of simultaneous use both for diagnosis and in the process of X-ray surgical treatment of various diseases of the lymphatic system and diseases associated with the lymphatic system.

[0024] The specified technical result is achieved in a method for dynamic 3D visualization of the lymphatic system, including X-ray visualization of the lymphatic bed, in which a bilateral puncture of the inguinal lymph nodes is performed with 25G needles under ultrasound control, followed by the simultaneous introduction of a water-soluble radiopaque agent into the inguinal lymph nodes on both sides at a rate of 1.0 ml / min for 10 minutes, after the start of the contrast supply, continuous fluoroscopy or digital subtraction angiography is performed, confirming the flow of contrast from the lymph node into the efferent lymphatic ducts and excluding its extravasation beyond the capsule, the first PDCT scanning of the area of ​​​​interest is performed before the start of the flow of contrast through the lymphatic system, then under the control of intermittent fluoroscopy, monitoring the dynamic flow of contrast through the lymphatic system is carried out,Upon reaching the area of ​​interest, repeated series of PDCT scans are performed, native, post-contrast multiplanar reconstructions and dynamic 3D models of the angiographic complex of the lymphatic bed are obtained in a single stereotactic space.

[0025] The method is illustrated in Fig. 1-8, where:

[0026] Fig. 1 - Correct placement of the catheter into the inguinal lymph node under U3 guidance.

[0027] Fig. 2 - presets for controlled administration of a water-soluble radiocontrast agent using a syringe injector for 10 minutes (injection rate 1.0 ml / min, volume of contrast agent - 10 ml).

[0028] Fig. 3 - visualization of contrast influx during continuous fluoroscopy.

[0029] Fig. 4 - visualization of the flow of contrast agent through the lymphatic pathways using intermittent fluoroscopy.

[0030] Fig. 5 - 3D reconstruction of lymph flow through the lymphatic vessels of the pelvis on the left - the location of lymph leakage into the retroperitoneal space on the left is determined.

[0031] Fig. 6 - pre-contrast PDCT before the administration of a contrast agent: multiple atherosclerotic plaques are determined on the walls of the infradiaphragmatic aorta, radiopaque bodies of the lumbar vertebrae, as well as the right ureter (yellow arrow).

[0032] Fig. 7 - PDCT scan 10 minutes after intranodal administration of contrast agent: the right and left lumbar lymphatic trunks and chyle cistern are visualized (blue arrow), but visualization of the left lumbar trunk is significantly complicated due to the superposition of high-contrast structures in the form of atherosclerotic plaques (yellow arrow) on this area.

[0033] Fig. 8 - Subtraction PDCT image obtained by subtracting the 3D pre-contrast scan data from the 3D post-contrast PDCT data. Both the right and left lumbar trunks are clearly visualized, with lymph leakage (yellow arrow) visible in the projection of the left lumbar trunk.

[0034] The method is carried out, for example, as follows.

[0035] 1. The first stage of the procedure involves ultrasound imaging of the inguinal lymph nodes on both sides. The patient lies supine with minimal hip abduction. An ultrasound machine with a 7-12 MHz linear transducer is used for navigation. To achieve optimal ultrasound projection, the lymph node should be displayed in longitudinal section (the length of the lymph node coincides with the scanning plane of the U3 transducer) in the central part of the screen. This position allows for the most accurate assessment of anatomical landmarks and selection of the optimal access point for subsequent puncture.

[0036] 2. After identifying the target lymph nodes, they are punctured on both sides using U3 guidance. To do this, using the hyperechoic structure of the lymph node hilum as a guide, a 25G spinal needle is inserted into the central portion of the node. The tip of the needle should be clearly visible on the screen as it enters the portal sinus (Fig. 1). This serves as a standard for technical accuracy and ensures proper intra-tissue positioning of the needle, preventing extravasation.

[0037] 3. The next step, after successful insertion, is to remove the stylet from the needles, and connect its proximal end to the contrast injection line. The system is pre-filled with a sterile, water-soluble radiocontrast agent containing at least 300 mg / ml of iodine without dilution. The infusion lines from both punctured inguinal lymph nodes are connected via a Y-connector to a standard syringe injector included with the angiographic system.

[0038] 4. The injection syringe is used to set the parameters for contrast agent administration: a constant rate of 1.0 ml / min (into each lymph node) for 10 minutes. These settings prevent hydraulic damage to the lymphatic sinuses and ensure uniform delivery of contrast to the central efferent collectors (Fig. 2).

[0039] 5. After the start of contrast agent administration, continuous fluoroscopy or DSA is performed for several seconds at maximum magnification to confirm the flow of contrast from the lymph node into the efferent lymphatic ducts and to exclude extravasation of contrast beyond the capsule (Fig. 3).

[0040] 6. Next, under the control of intermittent fluoroscopy, the dynamic flow of the contrast agent through the lymphatic system is monitored (Fig. 4).

[0041] 7. If necessary, upon reaching key anatomical (iliac conducting lymphatic system, lumbar lymphatic trunks, cisterna chyli, thoracic lymphatic duct, lymphovenous junction, etc.) or pathological (area of ​​contrast agent extravasation, extravasation dynamics, area of ​​lymphocele formation, pathological retrograde lymph flow, area of ​​thoracic lymphatic duct stenosis, reverse dermal flow, etc.) structures, repeat series of PDCT scans are performed, for example, in the DynaCT 6sDCT Body mode (for the Artis Zee Floor angiographic system (Siemens, Germany)), however, the first scan of the area of ​​interest is performed before the contrast agent begins to flow through the lymphatic system and is subsequently used for subtraction.

[0042] A graphical model of the contrast flow is generated in the angiographic software and allows for real-time acquisition of 3D spatial information on lymphatic circulation (Fig. 5). This reconstruction is crucial for diagnosis and planning of subsequent therapeutic X-ray surgical interventions—from percutaneous embolization of the lymph leak site to recanalization and stenting of the thoracic duct occlusion.

[0043] It should be noted that the initial PDCT scan of the area under study is performed before the contrast agent is injected (pre-contrast PDCT), and these data are then used for subsequent image subtraction from the contrast PDCT series. This allows, if necessary, to exclude bone structures and calcified plaques located in the aorta and large arteries, as well as soft tissue structures, from the analyzed data, significantly improving dynamic visualization of the lymphatic system. This scanning mode should be referred to as PDCT lymphangiography in 3D subtraction mode (Figs. 6, 7, 8).

[0044] 8. At the final stage, fluoroscopy and PDCT are used to assess the technical effectiveness of the surgical intervention. For example, the patency of the thoracic duct after stenting, the absence of pathological retrograde lymphatic flow after treatment of plastic bronchitis, or the absence of lymph leakage after embolization of the leak site. This is performed with continued radiographic monitoring or in PDCT mode, followed by analysis of the extent, integrity, presence of collaterals, backflow, or areas of dilation. If necessary, additional reconstruction can be performed with isolation of the segment of interest in a graphical model.

[0045] The method is confirmed by a clinical example.

[0046] Patient R., 76 years old, male. Preliminary clinical diagnosis before surgery: prostate cancer pT3bN1 (6 / 20)M0 ISUP5. Extremely high-risk group according to NCCN.

[0047] A laparoscopic radical prostatectomy with pelvic lymphadenectomy was performed in a hospital setting. Postoperative complications included lymphorrhea. Given the postoperative course and the significant complication noted above, lymphangiography and iliac lymph node embolization were performed under PDCT guidance.

[0048] A dynamic 3D visualization of the lymphatic system was performed using the method described above (Figs. 1-8). This procedure resulted in visualization and embolization of the lymph leak site, and post-procedure monitoring revealed no lymphorrhea.

[0049] In 2025, a total of 25 lymphangiographies were performed using the claimed method on 19 patients with complications following surgical treatment, such as lymphorrhea. In six cases, repeat patented interventions were performed due to the lack of desired effect after the first procedure. Ultimately, the effectiveness of the method was 100% for all patients. No serious complications were noted. All patients have been discharged from the hospital, and follow-up is ongoing.

[0050] Thus, the proposed method provides a step-by-step, strictly standardized, and technologically reproducible process, combining the capabilities of U3 navigation, fluoroscopic guidance, 3D modeling, and targeted intervention. This ensures not only precise visualization of the lymphatic system but also safe, simultaneous access for its treatment.

[0051] Sources of information

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[0054] 3. Parikh R., Seyferth E.R., Palat S., Itkin M., Nadolski G.J. Outcomes of Intranodal and Modified Intranodal Lymphangiography for Treatment of Traumatic Chylous Leaks in the Thorax and Neck. Cardiovasc Intervent Radiol. 2025;48(l):59-64. doi: 10.1007 / s00270-024-03900-z.

[0055] 4. Klotz R., Kuner C., Pan F., et al. Therapeutic lymphography for persistent chyle leak after pancreatic surgery. HPB (Oxford). 2022;24(5):616-623. doi: 10.1016 / j.hpb.2021.09.019.

[0056] 5. Kawasaki R., Sugimoto K., Fujii M., et al. Therapeutic effectiveness of diagnostic lymphangiography for refractory postoperative chylothorax and chylous ascites: correlation with radiologic findings and preceding medical treatment. AJR Am J Roentgenol. 2013;201(3):659-666. doi:10.2214 / AJR.12.10008.

[0057] 6. Jardinet Т., Veer H.V., Nafteux P., Depypere L., Coosemans W., Maleux G. Intranodal Lymphangiography With High-Dose Ethiodized Oil Shows Efficient Results in Patients With Refractory, High-Output Postsurgical Chylothorax: A Retrospective Study. AJR Am J Roentgenol. 2021;217(2):433-438. doi:10.2214 / AJR.20.23465.

[0058] 7. Pan F., Loos M., Do T.D., et al. Percutaneous afferent lymphatic vessel sclerotherapy for postoperative lymphatic leakage after previous ineffective therapeutic transpedal lymphangiography. Eur Radiol Exp.2020;4(1):60. doi: 10.1186 / s41747-020-00188-9.

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Claims

A method for dynamic 3D visualization of the lymphatic system, including radiographic visualization of the lymphatic bed using flat-detector computed tomography (FDCT), characterized in that bilateral puncture of the inguinal lymph nodes is performed with 25G needles under ultrasound control, followed by simultaneous administration of a water-soluble radiocontrast agent into the inguinal lymph nodes on both sides at a rate of 1.0 ml / min for 10 minutes, after the start of contrast delivery, continuous fluoroscopy or digital subtraction angiography is performed, confirming the flow of contrast from the lymph node into the efferent lymphatic ducts and excluding its extravasation beyond the capsule, the first FDCT scanning of the area of ​​​​interest is performed before the start of contrast flow through the lymphatic system, then under the control of intermittent fluoroscopy, monitoring the dynamic flow of contrast through the lymphatic system is carried out,Upon reaching the area of ​​interest, repeated series of PDCT scans are performed, native, post-contrast multiplanar reconstructions and dynamic 3D models of the angiographic complex of the lymphatic bed are obtained in a single stereotactic space.

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