Pulmonary Lymphatic Perfusion Research Articles

Dynamic Contrast-Enhanced Magnetic Resonance Lymphangiography and Lymphatic Interventions for Pediatric Patients with Various Lymphatic Diseases.

Background: To demonstrate the magnetic resonance lymphangiography (MRL) imaging findings of lymphatic diseases and the clinical outcomes of lymphatic embolization in pediatric patients. Methods and Results: This retrospective study included 10 consecutive pediatric patients who underwent MRL for lymphatic diseases between June 2017 and June 2021. Nine patients underwent dynamic contrast-enhanced MRL with bilateral inguinal lymph node injection of diluted gadolinium, and one patient underwent nonenhanced MRL with a heavily T2-weighted image. The etiology of lymphatic disease was classified into three categories based on the magnetic resonance findings. The resolution of chylous fluid and weight-adjusted amounts of chylous fluid collected from a drainage tube were evaluated as outcomes. Patients were classified as postoperative lymphatic leak (n = 3), pulmonary lymphatic perfusion syndrome (n = 3), central lymphatic flow disorder (CLFD; n = 3), and primary lymphatic dysfunction (Gorham-Stout syndrome; n = 1). Three patients underwent radiological lymphatic intervention, and one CLFD patient underwent surgical intervention. In patients with postoperative lymphatic leak, the median chest tube drainage decreased significantly after the intervention [from 87.9 to 12.4 mL/(kg·d); p = 0.02]. However, in one CLFD patient, the amount of chylous fluid did not decrease until 7 days after intervention. Conclusion: The etiology of lymphatic disease in pediatrics can be recognized on MRL, and lymphatic intervention can be performed for cessation of lymphatic leak, even though the treatment outcomes may differ according to the underlying etiology. MRL can play an important role in classifying lymphatic disease, and in planning treatment on the basis of the lymphatic anatomy and underlying etiology.

Abnormal Pulmonary Lymphatic Flow on Novel Lymphangiographic Imaging Supports a Common Etiology of Lymphatic Plastic Bronchitis and Nontraumatic Chylothorax.

Background: This study evaluates whether dynamic contrast-enhanced magnetic resonance lymphangiography (DCMRL) and thoracic duct lymphangiography (TDL) findings in adults with lymphatic plastic bronchitis (PB) and/or nontraumatic chylothorax (NTC) support a shared pathophysiology. Materials and Results: Retrospective review of clinical and imaging findings in patients who underwent DCMRL and TDL at a single institution from March 2017 to March 2019. Categorical variables were compared with Fisher's exact test. Twenty-eight patients (median age 61 ± 21 years, 15 women) presenting with lymphatic PB (n = 13), NTC (n = 10), or both (n = 5) were included. Lymphatic imaging demonstrated pulmonary lymphatic perfusion (PLP) in all patients. A patent thoracic duct (TD) with retrograde flow was seen in 53.4% (7/13) of patients with PB, 60% (6/10) of patients with NTC, and 20% (1/5) of patients with both (p = 0.69). An occluded TD with retrograde flow was seen in 30.8% (4/13) of patients with PB, 30% (3/10) of patients with NTC, and 80% (4/5) of patients with both (p = 0.12). Similar patterns of PLP between DCMRL and TDL were seen in 96.2% (25/26) of patients. Conclusions: DCMRL and TDL demonstrated similar findings in patients with lymphatic PB and/or NTC, supporting a common etiology. This supports the hypothesis that the clinical presentation depends on the proximity of abnormal lymphatic vessels to the pleural cavity, resulting in chylothorax, or bronchial mucosa, resulting in PB.

Case report: hepatobronchial lymphatic communications in single ventricle patients as a pathophysiological mechanism of plastic bronchitis: diagnosis and treatment.

Background Plastic bronchitis is a rare but devastating complication in single ventricle patients after Fontan completion. Recent advances in dynamic contrast-enhanced magnetic resonance lymphangiogram demonstrate the typical pathophysiological mechanism of the thoracic duct leaking lymphatic fluid towards the bronchi resulting in intraluminal casts. This has been termed abnormal pulmonary lymphatic perfusion and has been successfully treated in 94% of patients with thoracic duct occlusion. However, in some cases, this aberrant flow is not identified and therefore no intervention is available. This case report identifies a newly discovered origin of abnormal lymphatic flow from the liver to the bronchi and the treatment of these patients.Case summary We report two cases of plastic bronchitis in single ventricle patients with no identified abnormal lymphatic pulmonary perfusion from the thoracic duct. Both patients underwent liver lymphangiogram and demonstrated aberrant flow from the hepatic lymphatic ducts to the bronchi. These were successfully occluded, and plastic bronchitis symptoms resolved in both cases.Discussion The recent discovery of the abnormal pulmonary lymphatic perfusion from the thoracic duct to the bronchi has allowed successful treatment of 94% of single ventricle patients with plastic bronchitis. The discovery of hepatobronchial lymphatic perfusion reveals an occult aetiology of plastic bronchitis and a second target for embolization and successful treatment.

Neonatal lymphatic flow disorders: impact of lymphatic imaging and interventions on outcomes.

We conducted a retrospective study of 35 neonates with pulmonary lymphatic abnormalities at our institution who underwent lymphatic evaluation between December 2015 and September 2018. Patients with only pulmonary lymphatic perfusion syndrome were classified as NCTx and those with multiple flow abnormalities were classified as CLFD. Demographics, clinical characteristics, and outcomes were compared using t-tests/Wilcoxon rank sum tests and Fisher's exact tests. All 35 patients had intranodal MR lymphangiography and 14 (40%) also had conventional fluoroscopic lymphangiography. Fifteen (42.8%) patients were diagnosed with NCTx and 20 (57.1%) were diagnosed with CLFD. Thirty-four (97.1%) patients had pleural effusions. None of the NCTx group had ascites, anasarca, or dermal backflow compared to 17 (85%) (p < 0.001), 8 (42.1%) (p: 0.004), and 20 (100%) (p < 0.001) of the CLFD group, respectively. In the NCTx group, 11 (73.3%) had ethiodized oil embolization and 4 (26.7%) received conservative therapy. Ten (50%) of the CLFD patients had an intervention; of those, two (10%) had ethiodized oil-only embolization. Eight had non-ethiodized oil embolizations (two (25%) had embolization with glue, three (37.5%) underwent surgical lymphovenous anastomosis, two (25%) underwent thoracic duct (TD) externalization, and one (12.5%) had a non-TD lymphatic channel drain placed). Complete resolution of pleural effusions was achieved in all 15 NCTx patients, whereas 9 (45%) of 20 CLFD patients had resolution of chylothorax (p: 0.001). Establishing a diagnosis of NCTx or CLFD is paramount in selecting treatment options and providing prognostic information. Development of lymphatic interventions represents a paradigm shift in our understanding of neonatal lymphatic flow disorders and may be associated with improved survival.

Abstract No. 589 Utility of dynamic contrast magnetic resonance lymphangiography in the diagnosis and treatment of plastic bronchitis

Recently, intranodal lymphangiography (IL) and thoracic duct embolization (TDE) have been described as a treatment of plastic bronchitis. Additionally, dynamic contrast MR lymphangiography (DCMRL) has been used to detail the central lymphatic anatomy prior to TDE. The purpose of the present study is to examine the utility of preintervention DCMRL for treating patients with clinically diagnosed plastic bronchitis (PB). Review of IR QA database (Hi-IQ) was performed to identify patients referred for TDE. Between 2016-19, 46 patients (21F:25M, mean age 51 years) were referred to interventional radiology for treatment of clinically diagnosed PB. Medical records were reviewed for imaging (DCMRL and IL) findings and outcome of TDE. Of the 46 patients referred for PB, 37 underwent DCMRL prior to IL and TDE. Reasons pts did not undergo DCMRL included obesity (n = 7), pacemaker dependent (n = 1), and critically ill (n = 1). In 32/37 patients (86%), DCMRL demonstrated abnormal lymphatic perfusion of central bronchi or lungs arising from the TD indicating a lymphatic etiology of PB. In the remaining 5 subjects, lymphatic anatomy was normal. All 37 patients subsequently underwent IL and TD cannulation for TDE. IL/TDE confirmed aberrant lymphatic perfusion in 32/32 (100%) of patients with DCMRL findings diagnostic for lymphatic etiology of PB. In the 5 patients with normal DCMRL, the IL and cannulation of the TD were also normal. Lymphazurin blue was injected into the TD via a microcatheter while bronchoscopy was performed in these 5 patients, and none were found to have the dye appear in the submucosal lymphatics of the airway, further confirming abnormal pulmonary lymphatic perfusion was not present. The PPV and NPV of DCRML for lymphatic origin of PB was 100% (P <0.001). In the 32/37 patients with positive DCMRL, TDE was performed with coils and N-BCA glue. In 31/32 embolized patients, symptoms resolved completely. In one patient, symptoms resolved but recurred requiring a second TDE. DCRML has a high PPV and NPV for confirming a lymphatic etiology of PB. These findings suggest DCMRL should be performed on all patients with PB to confirm the etiology of PB prior to undergoing TDE.

Successful Percutaneous Lymphatic Intervention for Chylothorax after Pediatric Heart Transplantation

Purpose Chylothorax after pediatric heart transplantation (HTX) is a highly morbid and challenging disease often refractory to therapies including thoracic duct ligation or pleurodesis. We report our novel approach to lymphatic imaging and percutaneous intervention for chylothorax after HTx in children. Methods We reviewed our center's data on children with post-HTx chylothorax who underwent dynamic contrast-enhanced magnetic resonance lymphangiography (DCRL) and lymphatic embolization between November 2014 and November 2017. Results Four children (50% male, median age 5 ± 45 months) were referred for post-HTx chylothorax. Three underwent HTx for congenital heart disease (including 1 single ventricle) and 1 for dilated cardiomyopathy. Three had chylothorax immediately post-HTx associated with superior caval anastomosis obstruction or diastolic dysfunction and 1 developed chylothorax 6 months post-HTx during antibody-mediated rejection. Lymphatic imaging demonstrated abnormal pulmonary lymphatic perfusion syndrome in all 4 patients, with percutaneous interventions performed including thoracic duct or channel embolization (Figure: right - fluoroscopic image of contrast injected into thoracic duct; left - DCMRL inguinal lymph node injection; arrow highlight abnormal pulmonary perfusion; arrowhead identify thoracic duct). All 4 patients with chylothorax had complete resolution with a median 6.5 days from intervention to chest tube removal. Conclusion Chylothorax after pediatric HTx may result from abnormal pulmonary lymphatic perfusion that can be successfully treated with percutaneous lymphatic embolization. Factors associated with pulmonary lymphatic diseases after pediatric HTx include congenital heart disease and elevated central venous pressure due to SVC obstruction or rejection-mediated diastolic dysfunction. Chylothorax after pediatric heart transplantation (HTX) is a highly morbid and challenging disease often refractory to therapies including thoracic duct ligation or pleurodesis. We report our novel approach to lymphatic imaging and percutaneous intervention for chylothorax after HTx in children. We reviewed our center's data on children with post-HTx chylothorax who underwent dynamic contrast-enhanced magnetic resonance lymphangiography (DCRL) and lymphatic embolization between November 2014 and November 2017. Four children (50% male, median age 5 ± 45 months) were referred for post-HTx chylothorax. Three underwent HTx for congenital heart disease (including 1 single ventricle) and 1 for dilated cardiomyopathy. Three had chylothorax immediately post-HTx associated with superior caval anastomosis obstruction or diastolic dysfunction and 1 developed chylothorax 6 months post-HTx during antibody-mediated rejection. Lymphatic imaging demonstrated abnormal pulmonary lymphatic perfusion syndrome in all 4 patients, with percutaneous interventions performed including thoracic duct or channel embolization (Figure: right - fluoroscopic image of contrast injected into thoracic duct; left - DCMRL inguinal lymph node injection; arrow highlight abnormal pulmonary perfusion; arrowhead identify thoracic duct). All 4 patients with chylothorax had complete resolution with a median 6.5 days from intervention to chest tube removal. Chylothorax after pediatric HTx may result from abnormal pulmonary lymphatic perfusion that can be successfully treated with percutaneous lymphatic embolization. Factors associated with pulmonary lymphatic diseases after pediatric HTx include congenital heart disease and elevated central venous pressure due to SVC obstruction or rejection-mediated diastolic dysfunction.

Imaging of central lymphatic abnormalities in Noonan syndrome.

Children with Noonan syndrome are known to have increased risk for lymphatic disorders, the extent and nature of which are poorly understood. Our objective was to describe the imaging findings of the central lymphatic abnormalities in children with Noonan syndrome who underwent central lymphatic imaging. We conducted a single-center retrospective review of all children with a confirmed history of Noonan syndrome who presented for lymphatic imaging over a 5-year period. Imaging evaluation was performed on unenhanced T2-weighted (T2-W) imaging, dynamic-contrast MR lymphangiography or conventional lymphangiography. Two readers evaluated the imaging in consensus for the distribution of fluid on T2-W imaging and for lymphatic flow of intranodal contrast agent and thoracic duct abnormalities on dynamic-contrast MR lymphangiography and conventional lymphangiography. We performed a chart review for clinical history and outcomes. We identified a total of 10 children, all but one of whom had congenital heart disease. Presenting symptoms included chylothorax (n=9) and ascites (n=1). Nine had T2-W imaging, seven had dynamic-contrast MR lymphangiography, and seven had conventional lymphangiography. All with T2-W imaging had pleural effusions. On both dynamic-contrast MR lymphangiography and conventional lymphangiography, perfusion to the lung was seen (n=6), with intercostal flow also seen on dynamic-contrast MR lymphangiography (n=6). The thoracic duct was not present in three children and the central thoracic duct was not present in three. A double thoracic duct was seen in two children. Children with Noonan syndrome and clinical evidence of lymphatic dysfunction have central lymphatic abnormalities characterized by retrograde intercostal flow, pulmonary lymphatic perfusion, and thoracic duct abnormalities.

Dynamic Contrast-Enhanced Magnetic Resonance Lymphangiography and Percutaneous Lymphatic Embolization for the Diagnosis and Treatment of Recurrent Chyloptysis

Chyloptysis, or the expectoration of triglyceride-rich sputum, is rare and typically treated with diet modification and thoracic duct ligation. This article describes 2 patients with prolonged histories of chyloptysis who failed conservative treatment and thoracic duct ligation. Dynamic contrast-enhanced magnetic resonance imaging delineated the lymphatic anatomy and identified the abnormal pulmonary lymphatic perfusion pathways in both patients. This imaging provided guidance for successful percutaneous lymphatic embolization which resulted in resolution of symptoms in both patients.

MR Lymphangiography in Children: Technique and Potential Applications.

The lymphatic system, an important component of the circulatory system with essential physiologic functions, can be affected by various disease processes. There has been a delay in the development of effective imaging methods for the lymphatic system due to its small size, which limits visualization as well as introduction of contrast material. Traditionally, the lymphatic system has been imaged by injecting contrast material or radiotracers into the feet or hands. This is not sufficient for assessment of the central conducting lymphatics (CCLs) (such as the thoracic duct or the cisterna chyli). Fluoroscopic intranodal lymphangiography with injection of oil-based contrast material into groin lymph nodes improves visualization of CCLs but is limited in practice owing to the use of radiation and the potential risk for paradoxical embolization in children with left-to-right shunt. Dynamic contrast material-enhanced (DCE) magnetic resonance (MR) lymphangiography, which is performed by injecting gadolinium-based contrast material into groin lymph nodes, overcomes these limitations. T2-weighted imaging plays a complementary role to DCE MR lymphangiography in the assessment of CCLs. DCE MR lymphangiography demonstrates preserved integrity or any abnormality of the CCLs (including blockage or leak). The technique has recently been used in evaluating pulmonary lymphatic perfusion syndrome in children with plastic bronchitis, neonatal lymphatic flow disorders, and nontraumatic chylothorax. It is useful in identification of the source of chylous ascites and contributes to understanding of the anatomy of lymphatic malformations. It is successfully used for planning of embolization of aberrant lymphatic channels in a variety of lymphatic flow disorders. This review discusses the anatomy and function of the lymphatic system, the evolution of imaging of the lymphatic system, and DCE MR lymphangiography technique and its applications in children. ©RSNA, 2017.

Magnetic Resonance Lymphangiography and Lymphatic Embolization in the Treatment of Pulmonary Complication of Lymphatic Malformation.

Lymphatic malformations (LMs; especially those involving the central conducting lymphatic channels) are characterized by dysplastic and incompetent lymphatic channels in multiple tissues and organs. The major cause of mortality and morbidity in patients with thoracic LM is deterioration of pulmonary function due to chronic chylous effusions and progressive interstitial lung disease. The etiology of these pulmonary processes is unknown, although lymphatic involvement is certain. Understanding of the changes in the lymphatic anatomy in patients with LM has been hindered by difficulty of imaging of the lymphatic system. Recently developed dynamic contrast-enhanced magnetic resonance lymphangiography (DCMRL) allows dynamic MR imaging of the lymphatic system by injecting gadolinium contrast agent in the groin lymph nodes. Using this technique, pathological lymphatic flow from the central lymphatic system and/or retroperitoneal and mediastinal masses into lung parenchyma ("pulmonary lymphatic perfusion syndrome") has been demonstrated in patients with LM. This abnormal lymphatic perfusion overflows pulmonary parenchyma and results in deterioration of pulmonary function due to interstitial process and/or compression effect of chylous effusions. Percutaneous thoracic duct embolization or lymphatic interstitial embolization of the lymphatic masses results in cessation of the pulmonary lymphatic overflow and significant improvement in pulmonary symptoms in these patients.

Post-Operative Chylothorax in Patients With Congenital Heart Disease

BackgroundPost-operative chylothorax in patients with congenital heart disease is a challenging problem with substantial morbidity and mortality. Currently, the etiology of chylothorax is poorly understood and treatment options are limited. ObjectivesThis study aimed to report lymphatic imaging findings, determine the mechanism of chylothorax after cardiac surgery, and analyze the outcomes of lymphatic embolization. MethodsWe conducted a retrospective review of 25 patients with congenital heart disease and post-operative chylothorax who presented for lymphatic imaging and intervention between July 2012 and August 2016. ResultsBased on dynamic contrast-enhanced magnetic resonance lymphangiography and intranodal lymphangiography, we identified 3 distinct etiologies of chylothorax: 2 patients (8%) with traumatic leak from a thoracic duct (TD) branch, 14 patients (56%) with pulmonary lymphatic perfusion syndrome (PLPS), and 9 patients (36%) with central lymphatic flow disorder (CLFD), the latter defined as abnormal central lymphatic flow, effusions in more than 1 compartment, and dermal backflow. Patients with traumatic leak and PLPS were combined into 1 group of 16 patients without CLFD, of whom 14 (88%) had an intact TD. Sixteen patients underwent lymphatic intervention, including complete TD embolization. All 16 patients had resolution of chylothorax, with a median of 7.5 days from intervention to chest tube removal and 15 days from intervention to discharge. The 9 patients with CLFD were considered a separate group, of whom 3 (33%) had an intact TD. Seven patients underwent lymphatic intervention but none survived. ConclusionsMost patients in this study had nontraumatic chylothorax and dynamic contrast-enhanced magnetic resonance lymphangiography was essential to determine etiology. Lymphatic embolization was successful in patients with traumatic leak and PLPS and, thus, should be considered first-line treatment. Interventions in patients with CLFD were not successful to resolve chylothorax and alternate approaches need to be developed.

4:03 PMAbstract No. 310 - Pulmonary lymphatic perfusion syndrome in patients with plastic bronchitis: diagnosis and embolization treatment

4:03 PMAbstract No. 310 - Pulmonary lymphatic perfusion syndrome in patients with plastic bronchitis: diagnosis and embolization treatment

LYMPHATIC SYSTEM: A FORGOTTEN AREA?

Development of new methods of visualization of the lymphatic system and in the treatment of several pathologies associated with impaired lymph fl ow. The lymphatic system is an integral part of the circulation. One of the main functions of the lymphatic system is to transport residual interstitial fl uid from the tissue back to the venous system. Despite growing recognition of the role of the lymphatic system in many disease processes, the techniques for imaging and interventions on the lymphatic system have lagged behind the well-developed methods for imaging and interventions on the cardiovascular systems. This is primarily due to small size and variability in anatomy of the lymphatic vessels, and diffi culty of introducing contrast into lymphatic ducts. Due to lack of imaging and intervention options, the fl ow function of the lymphatic system was relatively ignored over the last few decades. Recently, there has been resurgence in the interest in the fl ow function of the interventions on the lymphatic system with the development of percutaneous minimally invasive techniques, such as thoracic duct embolization, to treat life threatening lymphatic leaks. Our group recently introduced two new methods of lymphatic imaging: intranodal lymphangiography and dynamic contrast MR lymphangiography. These methods have allowed further understanding of lymphatic anatomy, pathophysiology, lymphodynamics, as well as provi???ded guidance for novel minimally invasive lymphatic interventions. Using new techniques, the group discovered the causes and then developed treatments for several fatal conditions effecting single ventricle patients including plastic bronchitis and protein loosing enteropathy. Treatment for other conditions has evolved as well including congenital lymphodysplasia, chylothorax, and chylous ascites. The study of the liver lymphatic system has been little explored despite its signifi cant relevance as exampled in ascites formation in association with cirrhosis, one of the most recognized clinical manifestations of lymphatic vascular system disorders. Liver lymphangiogram is an additional minimally invasive technique that allows visualization of the liver lymphatics. Embolization of the liver lymphatic system has been proven to be curative for liver lymphorrea. Due to the lack of the imaging ability of the lymphatic system the understanding of these relationships lacked. Intranodal lymphangiogram, and liver lymphangiograms are one of the fi rst steps in attempt to understand these relationships. Embolization of the lymphatic system provides the opportunity to treat the abnormal lymphatic fl ows in conditions such as pulmonary lymphatic perfusion syndrome, liver cirrhosis, cardiac failure.

Percutaneous Lymphatic Embolization of Abnormal Pulmonary Lymphatic Flow as Treatment of Plastic Bronchitis in Patients With Congenital Heart Disease.

Plastic bronchitis is a potentially fatal disorder occurring in children with single-ventricle physiology, and other diseases, as well, such as asthma. In this study, we report findings of abnormal pulmonary lymphatic flow, demonstrated by MRI lymphatic imaging, in patients with plastic bronchitis and percutaneous lymphatic intervention as a treatment for these patients. This is a retrospective case series of 18 patients with surgically corrected congenital heart disease and plastic bronchitis who presented for lymphatic imaging and intervention. Lymphatic imaging included heavy T2-weighted MRI and dynamic contrast-enhanced magnetic resonance lymphangiogram. All patients underwent bilateral intranodal lymphangiogram, and most patients underwent percutaneous lymphatic intervention. In 16 of 18 patients, MRI or lymphangiogram or both demonstrated retrograde lymphatic flow from the thoracic duct toward lung parenchyma. Intranodal lymphangiogram and thoracic duct catheterization was successful in all patients. Seventeen of 18 patients underwent either lymphatic embolization procedures or thoracic duct stenting with covered stents to exclude retrograde flow into the lungs. One of the 2 patients who did not have retrograde lymphatic flow did not undergo a lymphatic interventional procedure. A total of 15 of 17(88%) patients who underwent an intervention had significant symptomatic improvement at a median follow-up of 315 days (range, 45-770 days). The most common complication observed was nonspecific transient abdominal pain and transient hypotension. In this study, we demonstrated abnormal pulmonary lymphatic perfusion in most patients with plastic bronchitis. Interruption of the lymphatic flow resulted in significant improvement of symptoms in these patients and, in some cases, at least temporary resolution of cast formation.

Primary ciliary dyskinesia and humoral immunodeficiency – what is the missing link?

Pulmonary lymphatic flow disorders involve the abnormal lymphatic flow via lymphatic channels to the lungs and pleural space. Plastic bronchitis and chylothorax are the main complications of this abnormal lymphatic perfusion, which has been termed pulmonary lymphatic perfusion syndrome (PLPS). Following lymphatic access, dynamic contrast MR lymphangiography is the imaging modality of choice to diagnose these disorders. Management includes medical therapy, percutaneous interventions under fluoroscopy, and surgical interventions.