ABSTRACT
Lymphedema, resulting from impaired lymphatic drainage, causes inflammation, fibrosis and tissue damage leading to symptoms such as limb swelling and restricted mobility. Despite various treatments under exploration, no standard effective therapy exists. Here a novel technique using the pyro-drive jet injection (PJI) was used to create artificial clefts between collagen fibers, which facilitated the removal of excess interstitial fluid. The PJI was used to deliver a mixture of lactated Ringer's solution and air into the tail of animals with secondary skin edema. Edema levels were assessed using micro-CT scanning. Histopathological changes and neovascularization were evaluated on the injury-induced regenerative tissue. Regarding tissue remodeling, we focused on connective tissue growth factor (CTGF) and vascular endothelial growth factor (VEGF)-C. PJI markedly diminished soft tissue volume in the experimental lymphedema animals compared to the non-injected counterparts. The PJI groups exhibited a significantly reduced proportion of inflammatory granulation tissue and an enhanced density of lymphatic vessels and α-smooth muscle actin (αSMA)-positive small vessels in the fibrous granulation tissue compared to the controls. In addition, PJI curtailed the prevalence of CTGF- and VEGF-C-positive cells in regenerative tissue. In a lymphedema animal model, PJI notably ameliorated interstitial edema, promoted lymphatic vessel growth, and bolstered αSMA-positive capillaries in fibrous granulation tissue. PJI's minimal tissue impact post-lymph node dissection indicates significant potential as an early, standard preventative measure. Easily applied in general clinics without requiring specialized training, it offers a cost-effective and highly versatile solution to the management of lymphedema.
Subject(s)
Lymphatic Vessels , Lymphedema , Animals , Vascular Endothelial Growth Factor A/metabolism , Lymphedema/therapy , Lymphedema/etiology , Lymphedema/pathology , Lymphatic Vessels/diagnostic imaging , Lymphatic Vessels/pathology , Skin/metabolism , Edema/complications , Edema/metabolism , Edema/pathologyABSTRACT
The establishment of new connections after NVLNT (non-vascularized lymph node transplantation) is still poorly understood. The purpose of this study was to investigate lymphatic connections after NVLNT using lymphangiography. In a mice model, 40 mice were allocated to undergo NVLNT or sham surgery. On day 21 after NVLNT, the lymphatic vessels were observed on near-infrared fluorescence imaging with indocyanine green. In a minipig model, 12 minipigs underwent NVLNT. On day 14 after NVLNT, the transplanted lymph node and donor site were checked by ultrasound, and minipigs with viable transplanted LNs were allocated to lipiodol lymphangiography or MR lymphangiography groups. Transplanted LN engraftment was examined with immunohistochemical staining. After NVLNT in mice, the signal intensities in the popliteal region at 3 minutes and 5 minutes were higher in the transplanted side than the control side (21.3 ± 8.1 vs. 11.0 ± 4.6 at 3 minutes, 26.7 ± 6.8 vs. 19.7 ± 5.9 at 5 minutes), while in the sham group, there were no significant differences between sides. In minipigs, lipiodol lymphangiography (n = 5) showed Lipiodol accumulation in transplanted LNs with innumerable newly formed lymphatic vessels and lymphovenous shunts. MR lymphangiography (n = 5) showed higher enhancement on the transplanted side compared to the control side. Histology showed successful engraftment of transplanted LNs in 16 out of 20 (80%) mice and 9 out of 12 (75%) minipigs. Omnidirectional lymphangiogenesis forming a dense lymphatic network and spontaneous formation of lymphovenous shunts were shown after NVLNT.
Subject(s)
Lymphatic Vessels , Lymphography , Swine , Animals , Mice , Lymphography/methods , Lymphangiogenesis , Ethiodized Oil , Swine, Miniature , Lymph Nodes/diagnostic imaging , Lymph Nodes/pathology , Lymphatic Vessels/diagnostic imaging , Lymphatic Vessels/pathologyABSTRACT
Resumen Introducción: El linfedema es una enfermedad inflamatoria crónica que afecta cerca de 250 millones de personas en el mundo. El tratamiento tradicional es la terapia descongestiva. Últimamente, existe la opción de complementar el tratamiento tradicional con procedimientos quirúrgicos fisiológicos como anastomosis linfáticovenosas y transferencia de linfonodos vascularizados. Sin embargo, la evidencia del uso de la terapia descongestiva en los cuidados pre y posoperatorios en estas cirugías es limitada. Objetivo: Evaluar el uso de terapia descongestiva como complemento a la cirugía de linfedema mediante anastomosis linfáticovenosas y transferencia de linfonodos vascularizados. Materiales y Método: Se realizó una revisión de la literatura en las siguientes bases de datos: Cochrane, Pubmed y Google académico, utilizando los siguientes términos mesh: "anastomosis, surgical", "lymphedema", "perioperative care", "microsurgery", "rehabilitation", "therapy", "lymph nodes", "bypass", "lymphedema and microsurgery". Se incluyó aquellos artículos que describían el uso de la terapia descongestiva en los cuidados pre- y posoperatorios. Resultados: Se identificó un total de 201 artículos y 12 fueron incluidos en el análisis. La evidencia reporta que las terapias más usadas en el cuidado pre- y posoperatorio son compresión, drenaje linfático manual y tratamientos personalizados. Sin embargo, la mayoría de los autores hace una descripción vaga de las terapias mencionadas. Discusión y Conclusión: La evidencia respecto al uso de terapia descongestiva como tratamiento complementario es débil. Los expertos recomiendan su uso, sin embargo, se necesitan futuras investigaciones que describan el uso de cada uno de sus componentes como complemento de procedimientos quirúrgicos fisiológicos para el manejo del linfedema.
Background: Lymphedema is a disease that affects about 250 million people around the world. The traditional treatment is decongestive therapy. In the past years, there is the option to complementing the traditional treatment with physiological surgical procedures such as lymphatic-venous anastomosis (LVA) and vascularized lymph node transfer (VLNT). However, the evidence for the use of decongestive therapy in pre- and post-operative care in these surgeries is limited. Aim: To evaluate the use of decongestive therapy as a complement to lymphedema surgery such a lymphatic-venous anastomosis and transfer of vascularized lymph nodes. Materials and Method: A literature review was carried out in the following databases: Cochrane, Pubmed and Academic Google, using the following mesh terms: "anastomosis, surgical", "lymphedema", "perioperative care", "microsurgery", "rehabilitation", "therapy", "lymph nodes","bypass", "lymphedema and microsurgery". "Those articles that described the use of decongestive therapy in pre- and post-operative care were included. Results: 201 articles were identified and 12 were included in the analysis. The evidence reports that the most used therapies in pre- and post-operative care are compression, manual lymphatic drainage and personalized treatments. However, most of the authors give a vague description of the mentioned therapies. Discussion and Conclusion: The evidence regarding the use of decongestive therapy as a complementary treatment is weak. Experts recommend its use; however, future research is needed to describe the use of each of its components as a complement to physiological surgical procedures for the management of lymphedema.
Subject(s)
Humans , Lymphatic Vessels/surgery , Lymphatic Vessels/diagnostic imaging , Lymphangitis/surgery , Lymphedema/surgery , Lymphedema/etiology , Neoplasms/surgery , Neoplasms/complications , Software Design , Anastomosis, Surgical/methods , Treatment Outcome , Lymph Nodes , Microsurgery/methodsABSTRACT
Unlike humans, the zebrafish can repair and regenerate its heart following injury. Understanding the molecular and physiological mechanisms of heart regeneration is critical in developing pro-regenerative strategies for clinical application. The cardiac lymphatic and non-lymphatic vasculature both respond to injury in zebrafish and are instrumental in driving optimal repair and regeneration. However, progress has been impeded by an inability to obtain high resolution images to clearly visualize and thus to fully understand the vascular responses in the injured heart and how this might intersect with successful repair and regeneration in humans.In this chapter, we describe a chemical clearing approach using Clear Unobstructed Brain/Body Imaging Cocktails and Computational analysis (CUBIC), for obtaining high resolution images of the adult zebrafish heart. This approach permits three-dimensional reconstruction of cardiac vasculature throughout the entire organ. By applying CUBIC methodology to tissues from transgenic zebrafish reporter lines or in conjunction with immunofluorescent staining, optical slices can be be generated, negating the need for standard tissue processing and sectioning procedures and yielding higher resolution images. The resultant images enable a holistic view of the coronary blood and lymphatic vasculature during heart injury and regeneration. Herein, we describe our protocol for visualizing vessels in the adult zebrafish heart using these approaches.
Subject(s)
Lymphatic Vessels , Zebrafish , Animals , Animals, Genetically Modified , Heart/diagnostic imaging , Heart/physiology , Imaging, Three-Dimensional , Lymphatic Vessels/diagnostic imaging , Zebrafish/physiologyABSTRACT
We used specific histochemical fluorescence-microscopic method of visualization of catecholamines to study adrenergic innervation of the thyroid gland tissue, blood vessels of the thyroid gland, cervical lymphatic vessel and lymph nodes in rats during correction of hypothyroidism with a bioactive formulation (Vozrozhdenie Plus balm with Potentilla alba L.). In experimental hypothyroidism, adrenergic innervation of the thyroid gland and the wall of the cervical lymph node, concentrated mainly along the arterial vessels and the cervical lymphatic vessel, retained its structural formations (plexuses and varicosities), but diffusion of catecholamines outside these formations was observed. Correction with the bioactive formulation restored of the contours of the nerve plexuses and varicosities and their brighter fluorescence in the thyroid gland and cervical lymphatic vessel and node. During correction of hypothyroidism with the bioactive formulation, reorganization of regional lymphatic vessels and nodes was more pronounced than reorganization of the thyroid gland.
Subject(s)
Hypothyroidism , Lymph Nodes/pathology , Lymphatic Vessels/pathology , Thyroid Gland/blood supply , Thyroid Gland/innervation , Adrenergic Fibers/drug effects , Adrenergic Fibers/pathology , Adrenergic Fibers/ultrastructure , Animals , Blood Vessels/diagnostic imaging , Blood Vessels/drug effects , Blood Vessels/pathology , Hypothyroidism/diagnostic imaging , Hypothyroidism/drug therapy , Hypothyroidism/pathology , Lymph Nodes/diagnostic imaging , Lymph Nodes/drug effects , Lymphatic Vessels/diagnostic imaging , Lymphatic Vessels/drug effects , Male , Microscopy, Fluorescence , Plant Extracts/pharmacology , Plant Extracts/therapeutic use , Potassium Iodide/pharmacology , Potassium Iodide/therapeutic use , Rats , Thyroid Gland/diagnostic imaging , Thyroid Gland/drug effects , Thyroid Hormones/pharmacology , Thyroid Hormones/therapeutic useABSTRACT
BACKGROUND: Lymphocele is a collection of lymphatic fluid within the body. It is caused by an impairment of lymph drainage and often occurs after a surgical intervention. In this setting conservative treatment is usually ineffective. The aim of this report is to share the outcomes of 11 patients with iatrogenic lymphocele in the thigh area treated by supermicrosurgical lymphovenous anastomosis. PATIENTS AND METHODS: Eleven patients presenting iatrogenic lymphocele in the thigh were referred for surgery after an unsuccessful conservative therapy. Patients' mean age was 56 years old, two males and nine females. All of them presented a moderate-to-severe lymphocele in the medial thigh after a surgical intervention that damaged the rich lymphatic pathway present there. Indocyanine green (ICG) lymphography was always performed to visualize the lymphatic vessels and to make the preoperative marking. RESULTS: All the 11 patients were successfully treated by means of one or more (range: 1-3; mean: 1.5) lymphaticovenous anastomoses without complications. Three of them also received a pedicled sartorius flap for dead space obliteration. All the patients reached full range of motion (ROM) and no recurrences were observed during follow up (range: 6-12 months; mean: 8). Intra-operative ICG lymphography was performed in all cases to check the patency of the anastomoses. CONCLUSIONS: Lymphaticovenous anastomosis confirmed to be a minimally-invasive and effective procedure for the treatment of postsurgical lymphoceles in the leg. For large lymphoceles a muscle flap may be indicated for volume restoration and prevention of recurrences.
Subject(s)
Lymphatic Vessels , Lymphedema , Lymphocele , Anastomosis, Surgical/adverse effects , Female , Humans , Iatrogenic Disease , Indocyanine Green , Lymphatic Vessels/diagnostic imaging , Lymphatic Vessels/surgery , Lymphocele/etiology , Lymphocele/surgery , Lymphography , Male , Neoplasm Recurrence, Local , Thigh/surgery , Treatment OutcomeABSTRACT
Lymphatic ascites after pelvic lymphadenectomy is a rare complication and is rarely reported after urologic surgery. We report a case of delayed and refractory lymphatic ascites following robotic-assisted laparoscopic radical prostatectomy.
Subject(s)
Ascites/etiology , Chylous Ascites/etiology , Lymphatic Vessels/injuries , Postoperative Complications/etiology , Prostatectomy/methods , Prostatic Neoplasms/surgery , Aged , Ascites/diagnostic imaging , Ascites/therapy , Chylous Ascites/diagnostic imaging , Chylous Ascites/therapy , Ethiodized Oil/therapeutic use , Humans , Lymph Node Excision/adverse effects , Lymph Node Excision/methods , Lymphatic Vessels/diagnostic imaging , Lymphography , Male , Paracentesis , Postoperative Complications/diagnostic imaging , Postoperative Complications/therapy , Recurrence , Robotic Surgical Procedures , Vena Cava Filters , Vena Cava, InferiorABSTRACT
Background: The influence of pulsed electromagnetic field therapy (PEMFT) on medium-sized vessels as well as capillary microcirculation is well known. Effects on lymphatic vessels, however, are difficult to visualize and have not been investigated to date. One of the operative treatment options in primary and secondary lymphedemas is lymphovenous anastomoses using supermicrosurgery. To prove patency of the anastomosis, the lymphatic flow is visualized by fluorescence using indocyanine green. The aim of this study was to investigate the influence of PEMFT on the lymphatic microcirculation, and compare it with conventional manual lymphatic drainage (MLD) during supermicrosurgery. Methods and Results: Ten patients with lymphedema were included. Indocyanine green was injected before the operation for intraoperative visualization of the lymphatic vessels using a microscope equipped with an integrated near-infrared illumination system (Zeiss). The PEMFT system (Bio-Electro-Magnetic-Energy Regulation [BEMER]) was used as our standard device during a single 2-minute application period (AP) followed by MLD or vice versa. The mean light intensity in the calibration period (CP) was 46.53 ± 24.3 and 33.41 ± 12.92 for PEMFT and MLD, respectively. During the AP, the mean light intensity changed to 45.61 ± 24.40 for PEMFT and 57.05 ± 18.80 during MLD. This change between CP and AP did not differ significantly for the PEMFT application (p = 0.26), but showed an increase in light intensity during MLD (p < 0.001). Conclusion: We found a light intensity enhancement equivalent to a flow increase during MLD of 78.7% ± 45.7% (range 20%-144%) and no significant difference during the PEMFT application. A single period application of PEMFT did not affect the lymphatic flow.
Subject(s)
Lymphatic Vessels , Lymphedema , Magnetic Field Therapy , Microsurgery , Electromagnetic Fields , Humans , Indocyanine Green , Lymphatic Vessels/diagnostic imaging , Lymphedema/therapy , Lymphography , Manual Lymphatic DrainageABSTRACT
Isolated penile lymphedema is a rare but severely disabling condition due to reduced lymphatic drainage. In this area treatment opportunities are poor being that conservative management is usually not effective and surgery limited to debulking lymphangiectomy, which is indicated only in very severe cases. Lymphovenous anastomosis (LVA) has a demonstrated efficacy in treatment of upper and lower limbs lymphedema but still has few applications in genital lymphedema and none when the swelling is confined in the penis. Here we present a case of an isolated penile lymphedema treated with super-microsurgical LVA. A 33-year-old patient presented swelling and pain immediately after a traumatic injury at the base of the penis. After 2 years of conservative praxis with manual lymphatic drainage of the penis and upper thigh bandage compression, no improvement of the symptoms was obtained. Indocyanine green lymphography was performed with dye injection in the glans confirming the diagnosis by showing lymphatic drainage stasis (dermal backflow). We consequently decided to undergo a surgical procedure performing lymphovenous anastomosis at the dorsum of the penis. Immediately following this intervention, both objective and subjective symptoms relief were noted with decrease of swelling and pain. The postoperative course was uneventful and at the 6 months follow up the patient reported no recurrence of the swelling even with the complete removal of compression therapy. We consider therefore that LVA may be a valid possibility for management of similar cases to provide a definitive clinical improvement.
Subject(s)
Lymphatic Vessels , Lymphedema , Adult , Anastomosis, Surgical , Humans , Lymphatic Vessels/diagnostic imaging , Lymphatic Vessels/surgery , Lymphedema/surgery , Lymphography , Male , Vascular Surgical ProceduresABSTRACT
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.
Subject(s)
Bronchitis/diagnostic imaging , Chylothorax/diagnostic imaging , Lymphatic Vessels/diagnostic imaging , Lymphography , Magnetic Resonance Imaging , Adolescent , Bronchitis/therapy , Child , Child, Preschool , Chylothorax/therapy , Contrast Media , Diet Therapy , Dietary Supplements , Disease Management , Embolization, Therapeutic , Humans , Infant , Lung Diseases/diagnostic imaging , Lung Diseases/therapy , Lymphatic Abnormalities/diagnostic imaging , Lymphatic Abnormalities/therapy , Lymphatic Diseases/diagnostic imaging , Lymphatic Diseases/therapy , Lymphatic Vessels/abnormalities , Lymphatic Vessels/surgery , MicrosurgeryABSTRACT
BACKGROUND: Breast cancer related lymphoedema (BCRL) is a common side effect of cancer treatment. Recently indocyanine green (ICG) fluorescent lymphography has become a popular method for imaging the lymphatics, however there are no standard protocols nor imaging criteria. We have developed a prospective protocol to aid in the diagnosis and therapeutic management of BCRL. METHODS: Lymphatic imaging procedures were conducted in three phases. Following initial observation of spontaneous movement of ICG in phase one, manual lymphatic drainage (MLD) massage was applied to facilitate ICG transit via the lymphatics in phase two. All imaging data was collected in phase three. Continuous lymphatic imaging of the upper limb was conducted for approximately an hour and lymphatic drainage pathways were determined. Correlations between the drainage pathway and MD Anderson Cancer Centre (MDACC) ICG lymphoedema stage were investigated. RESULTS: One hundred and three upper limbs with BCRL were assessed with this new protocol. Despite most of the patients having undergone axillary node dissection, the ipsilateral axilla drainage pathway was the most common (67% of upper limbs). We found drainage to the ipsilateral axilla decreased as MDACC stage increased. Our results suggest that the axillary pathway remained patent for over two-thirds of patients, rather than completely obstructed as conventionally thought to be the case for BCRL. CONCLUSIONS: We developed a new ICG lymphography protocol for diagnosing BCRL focusing on identification of an individual patient's lymphatic drainage pathway after lymph node surgery. The new ICG lymphography protocol will allow a personalised approach to manual lymphatic drainage massage and potentially surgery.
Subject(s)
Breast Cancer Lymphedema/diagnostic imaging , Coloring Agents/chemistry , Indocyanine Green/chemistry , Lymphography/methods , Manual Lymphatic Drainage/methods , Aged , Axilla/surgery , Female , Fluorescence , Humans , Lymph Node Excision , Lymphatic Vessels/diagnostic imaging , Lymphoscintigraphy/methods , Middle Aged , Prospective Studies , Retrospective Studies , Upper Extremity/diagnostic imagingABSTRACT
OBJECTIVE: Interstitial fluid in extracellular matrices may not be totally fixed but partially flow through long-distance oriented fibrous connective tissues via physical mechanisms. We hypothesized there is a long-distance interstitial fluid transport network beyond vascular circulations. MATERIALS AND METHODS: We first used 20 volunteers to determine hypodermic entrant points to visualize long-distance extravascular pathway by MRI. We then investigated the extravascular pathways initiating from the point of thumb in cadavers by chest compressor. The distributions and structures of long-distance pathways from extremity ending to associated visceral structures were identified. RESULTS: Using fluorescent tracer, the pathways from right thumb to right atrium wall near chest were visualized in seven of 10 subjects. The cutaneous pathways were found in dermic, hypodermic and fascial tissues of hand and forearm. The perivascular pathways were along the veins of arm, axillary sheath, superior vena cava and into the superficial tissues on right atrium. Histological and micro-CT data showed these pathways were neither blood nor lymphatic vessels but long-distance oriented fibrous matrices, which contained the longitudinally assembled micro-scale fibres consistently from thumb to superficial tissues on right atrium. CONCLUSIONS: These data revealed the structural framework of the fibrous extracellular matrices in oriented fibrous connective tissues was of the long-distance assembled fibres throughout human body. Along fibres, interstitial fluid can systemically transport by certain driving-transfer mechanisms beyond vascular circulations.
Subject(s)
Connective Tissue/metabolism , Extracellular Matrix/metabolism , Acupuncture Points , Adult , Cadaver , Connective Tissue/chemistry , Connective Tissue/pathology , Contrast Media/chemistry , Contrast Media/metabolism , Female , Fluorescein/chemistry , Fluorescein/metabolism , Foot/diagnostic imaging , Hand/diagnostic imaging , Humans , Lymphatic Vessels/anatomy & histology , Lymphatic Vessels/diagnostic imaging , Magnetic Resonance Imaging , Male , Microscopy, Confocal , Quantum Dots/chemistry , Quantum Dots/metabolism , Young AdultABSTRACT
BACKGROUND: Hybrid positron emission tomography (PET)-magnetic resonance imaging (MRI) systems have been taken in use as new clinical diagnostic tools including detection and therapy planning of cancer. To reduce the amount of contrast agents injected in patients while fully benefitting both modalities, dual-modality probes are required. MATERIAL AND METHODS: This study was first aimed at developing a hybrid PET-MRI probe by labeling superparamagnetic iron oxide nanoparticles (SPIONs) with 64Cu using a fast and chelator-free conjugation method, and second, to demonstrate the ability of the agent to target sentinel lymph nodes (SLNs) in vivo using simultaneous PET-MRI imaging. RESULTS: High labeling efficiency of 97% produced within 10-15 min was demonstrated at room temperature. 64Cu-SPIONs were chemically stable in mouse serum for 24 h and after intradermal injection in the hind paw of C57BL/6J mice, demonstrated specific accumulation in the SLN. Simultaneous PET-MRI clearly demonstrated visualization of 64Cu-SPIONs, in dynamic and static imaging sequences up to 24 h after administration. CONCLUSION: The use of a single hybrid probe and simultaneous hybrid imaging provides an efficient, complementary integration of quantitation and is expected to improve preoperative planning and intraoperative guidance of cancer treatments.
Subject(s)
Contrast Media/administration & dosage , Lymphatic Vessels/diagnostic imaging , Magnetic Resonance Imaging/methods , Multimodal Imaging/methods , Positron-Emission Tomography/methods , Animals , Contrast Media/chemistry , Contrast Media/pharmacokinetics , Copper Radioisotopes/administration & dosage , Copper Radioisotopes/pharmacokinetics , Drug Evaluation, Preclinical , Female , Image Processing, Computer-Assisted , Magnetite Nanoparticles/administration & dosage , Magnetite Nanoparticles/chemistry , Mice, Inbred C57BL , Radioactive Tracers , Tissue DistributionABSTRACT
Pre-clinical research in rodents provides evidence that the central nervous system (CNS) has functional lymphatic vessels. In-vivo observations in humans, however, are not demonstrated. We here show data on CNS lymphatic drainage to cervical lymph nodes in-vivo by magnetic resonance imaging (MRI) enhanced with an intrathecal contrast agent as a cerebrospinal fluid (CSF) tracer. Standardized MRI of the intracranial compartment and the neck were acquired before and up to 24-48 hours following intrathecal contrast agent administration in 19 individuals. Contrast enhancement was radiologically confirmed by signal changes in CSF nearby inferior frontal gyrus, brain parenchyma of inferior frontal gyrus, parahippocampal gyrus, thalamus and pons, and parenchyma of cervical lymph node, and with sagittal sinus and neck muscle serving as reference tissue for cranial and neck MRI acquisitions, respectively. Time series of changes in signal intensity shows that contrast enhancement within CSF precedes glymphatic enhancement and peaks at 4-6 hours following intrathecal injection. Cervical lymph node enhancement coincides in time with peak glymphatic enhancement, with peak after 24 hours. Our findings provide in-vivo evidence of CSF tracer drainage to cervical lymph nodes in humans. The time course of lymph node enhancement coincided with brain glymphatic enhancement rather than with CSF enhancement.
Subject(s)
Arachnoid Cysts/diagnostic imaging , Glymphatic System/diagnostic imaging , Hydrocephalus/diagnostic imaging , Intracranial Hypertension/diagnostic imaging , Intracranial Hypotension/diagnostic imaging , Lymphatic System/diagnostic imaging , Adult , Aged , Arachnoid Cysts/cerebrospinal fluid , Arachnoid Cysts/physiopathology , Cohort Studies , Contrast Media/administration & dosage , Female , Glymphatic System/metabolism , Glymphatic System/physiopathology , Humans , Hydrocephalus/cerebrospinal fluid , Hydrocephalus/physiopathology , Injections, Spinal , Intracranial Hypertension/cerebrospinal fluid , Intracranial Hypertension/physiopathology , Intracranial Hypotension/cerebrospinal fluid , Intracranial Hypotension/physiopathology , Lymph Nodes/diagnostic imaging , Lymph Nodes/metabolism , Lymph Nodes/physiopathology , Lymphatic System/metabolism , Lymphatic System/physiopathology , Lymphatic Vessels/diagnostic imaging , Lymphatic Vessels/metabolism , Lymphatic Vessels/physiopathology , Lymphography , Magnetic Resonance Imaging , Male , Middle Aged , Organometallic Compounds/administration & dosage , Parahippocampal Gyrus/diagnostic imaging , Parahippocampal Gyrus/metabolism , Parahippocampal Gyrus/physiopathology , Parenchymal Tissue/diagnostic imaging , Parenchymal Tissue/metabolism , Parenchymal Tissue/physiopathology , Pons/diagnostic imaging , Pons/metabolism , Pons/physiopathology , Prefrontal Cortex/diagnostic imaging , Prefrontal Cortex/metabolism , Prefrontal Cortex/physiopathology , Thalamus/diagnostic imaging , Thalamus/metabolism , Thalamus/physiopathologyABSTRACT
BACKGROUND: Near-infrared fluorescence (NIRF) imaging is a new imaging technique that is used to visualize lymphatic vessels in humans. It has a high spatial and temporal resolution, allowing real-time visualization of lymphatic flow. METHODS AND RESULTS: The current study investigated the intra- and inter-individual variability of the technique, and how local hypo- and hyperthermia (20°C, 40°C), as well as exercise affect lymph transport. In this study, 10 healthy volunteers were studied twice, with 2 weeks between. NIRF imaging was conducted by using intradermal Indocyanine green injections and a custom-built camera setup. All data were blinded before analysis and presented as mean ± standard deviation. Mean contraction frequency and lymph propulsion velocity were 0.59 ± 0.13 minutes-1 and 1.51 ± 0.24 cm/s, respectively, with no significant difference during each 4 hours examination or between the two visits. The maximal pressure that the lymphatic flow in the vessels could overcome on test day 1 and 2 was 56 ± 9 mmHg and 57 ± 9 mmHg, respectively (p = 0.496). Local hyperthermia increased contraction frequency from 0.62 ± 0.4 minutes to 1.46 ± 0.5 minutes-1 (p < 0.05). Hypothermia caused no significant changes. Immediately after exercise (exercising at a simulated distance of 1.4 km on a cycle ergometer), an increase in lymph propulsion velocity from 1.5 ± 0.49 to 2.2 ± 0.63 cm/s was observed (p < 0.05); whereas contraction frequency was unaltered. A decrease in contraction frequency from 0.68 ± 0.25 minutes to 0.35 ± 0.19 minutes-1 was observed 10 minutes after exercise, without a change in velocity. CONCLUSIONS: NIRF imaging can be conducted for 4 hours without a change in lymphatic activity. Furthermore, it has the sensitivity to detect changes in lymphatic activity by local hyperthermia and exercise. No changes were seen after local hypothermia. Pumping pressure shows good repeatability, whereas the other parameters show poor repeatability.
Subject(s)
Lymphatic Vessels/diagnostic imaging , Lymphography , Optical Imaging , Spectroscopy, Near-Infrared , Adult , Fluorescent Dyes , Humans , Hydrodynamics , Hyperthermia, Induced/methods , Hypothermia, Induced/methods , Indocyanine Green , Lymph , Lymphography/methods , Lymphography/standards , Male , Optical Imaging/methods , Optical Imaging/standards , Pressure , Reproducibility of Results , Spectroscopy, Near-Infrared/methods , Spectroscopy, Near-Infrared/standards , Young AdultABSTRACT
BACKGROUND: Lymphedema is a chronic peripheral swelling caused by a dysfunction of the lymphatic system, leading to discomfort and loss of upper limb movement. Therapies to treat or manage this swelling have limited evidence, partly because of a paucity in objective lymphatic measures. This study explored the role of near-infrared (NIR) imaging in evaluating interventions. METHODS: Nine healthy volunteers underwent NIR fluoroscopy using a microdose (50 µL, 0.05% w/v) of indocyanine green to quantify lymphatic behavior before and after a 15-minute period of manual lymph drainage followed by compression garment (CG) therapy for a 10-minute period. Images were taken at the forearm and elbow after each intervention. Lymphatic function was defined by the number, size, displacement, and speed of lymph packets. The lymph parameters were analyzed to assess the effects of the interventions compared with basal values. RESULTS: Baseline (BL) parameters of lymph function revealed high variability in the number, size, and speed of packets between individuals. Despite this variance, both interventions showed statistically significant improvement (p < 0.05) in displacement and speed at the forearm compared with BL. The velocity of transient lymph packets increased from a median of 6.7 mm/s at BL to 13.3 mm/s after manual lymphatic drainage (MLD) and 10.5 mm/s after CG. CONCLUSION: Lymphatic activity increased significantly after MLD, with relative increases being maintained after a short time period of CG application. NIR fluoroscopy has the potential to both monitor lymph pathology and provide robust parameters in the assessment of interventions.
Subject(s)
Lymphedema/diagnosis , Lymphedema/therapy , Lymphography , Manual Lymphatic Drainage , Spectroscopy, Near-Infrared , Stockings, Compression , Female , Fluorescent Dyes , Forearm/physiopathology , Humans , Lymphatic Vessels/diagnostic imaging , Lymphatic Vessels/physiopathology , Lymphedema/etiology , Lymphedema/physiopathology , Lymphography/methods , Manual Lymphatic Drainage/methods , Optical ImagingABSTRACT
The objective of this study was to evaluate the transport of radiotracers in lymphatic collectors during manual lymphatic therapy. The legs of four male and two female patients with leg lymphedema were assessed using lymphoscintigraphy before, during and after manual lymphatic therapy. The ages of the patients, treated in Hospital de Base in Sao Jose do Rio Preto, ranged from 42 to 64 years with a mean age of 51.2 years. Consecutive patients with grade II leg lymphedema were enrolled in this study. Patients with lymphedema secondary to lymphadenectomy, active infections and weight greater than 130 kg were excluded. Patients were submitted to manual lymphatic therapy, which consists of the collapsing of capillaries using manual compression which is then slid along the skin in a stroking action in the direction of the lymph flow within lymphatic vessels towards the lymph nodes. Two dynamic studies were performed; the first was over 40 minutes (3 images every 10 minutes) which was immediately followed by an entire body scan. A second dynamic evaluation was performed taking images at 10-second intervals over 2 minutes during manual lymphatic therapy. To evaluate the displacement of radiotracers, the path of lymphatic collectors from the knee to a lymph node in the upper thigh was divided into five similarly sized regions of interest. The concentration of radiotracer was quantified in each of the regions of interest. The paired t-test was used for statistical analysis with an alpha error of 5% (p value < 0.05) being considered statistically relevant. The results show statistically significant differences in the number of particles in all the regions of interest comparing before and after treatment (two-tail paired t-test: p value < 0.0001). Manual lymphatic therapy improves the transport of radiotracers in lymphatic collectors.
Subject(s)
Lymphedema/therapy , Lymphoscintigraphy , Musculoskeletal Manipulations/methods , Adult , Female , Humans , Hydrodynamics , Leg/pathology , Lymphatic Vessels/diagnostic imaging , Lymphatic Vessels/pathology , Lymphedema/diagnostic imaging , Male , Middle Aged , Reproducibility of Results , Treatment OutcomeABSTRACT
The effects of stimulation with sound and ultrasonic waves of a specific bandwidth on the microdissection of primo vessels in lymphatic vessels of rabbit were investigated. The primo vessels stained with alcian-blue dye injected in the lymph nodes were definitely visualized and more easily isolated by sound-wave vibration and ultrasonic stimulation applied to rabbits at various frequencies and intensities. With sound wave at 7 Hz and ultrasonic waves at 2 MHz, the probability of detecting the primo vessels was improved to 90%; however, without wave stimulation the probability of discovering primo vessels was about 50% only. Sound and ultrasonic waves at specific frequency bands should be effective for microdissection of the primo vessels in the abdominal lymph of rabbit. We suggest that oscillation of the primo vessels by sound and ultrasonic waves may be useful to visualize specific primo structure, and wave vibration can be a very supportive process for observation and isolation of the primo vessels of rabbits.
Subject(s)
Lymphatic Vessels/anatomy & histology , Lymphatic Vessels/diagnostic imaging , Meridians , Animals , Female , Rabbits , Sound , UltrasonographyABSTRACT
Lymphaticovenous anastomosis (LVA) is a treatment for lymphoedema that can improve lymph circulation by the anastomosis of lymph vessels and veins. A therapeutic effect of LVA for lymphoedema has been shown in limbs, but efficacy for other regions has not been shown. Lymphoedema in the head-and-neck region following cancer resection and radiotherapy is mainly treated with manual lymphatic drainage. However, there is no alternative when this treatment is ineffective because application of compression treatment using a bandage is difficult in this region. We used LVA for lymphoedema in the head-and-neck region and achieved a good outcome. Functional and dilating lymph vessels were identified using pre- and intra-operative fluorescent lymphography, and a lymph vessel with a diameter of about 0.2-1.0 mm was anastomosed with a vein using supermicrosurgery. The outcome of this case suggests that LVA is applicable for treatment of lymphoedema in the head-and-neck region.
Subject(s)
Anastomosis, Surgical , Head and Neck Neoplasms/therapy , Lymphatic Vessels/surgery , Lymphedema/etiology , Lymphedema/surgery , Veins/surgery , Face , Humans , Lymphatic Vessels/diagnostic imaging , Male , Microsurgery , Middle Aged , Postoperative Complications , Radiography , Radiotherapy/adverse effectsABSTRACT
Secondary lymphedema of external male genital organs is a frequent complication of pelvic radical surgery following pelvic lymphadenectomy. Microsurgical lymphovenous anastomoses are usually performed using only the superficial scrotal lymphatics, excluding testicular lymphatic drainage. We have experimented using a new microsurgical technique based on lymphovenous anastomosis between the collectors of the spermatic funiculus and the veins of the pampiniform plexus, allowing testicular lymphatic drainage. The study included 11 patients with external genital organ lymphedema, five of whom were subjected to microsurgical lymphovenous derivation. At 3, 6, and 12 mo after surgery, the patency of lymphovenous anastomoses was assessed by noninvasive lymphography using indocyanine green fluorescence images obtained with the Photodynamic Eye (PDE) infrared camera system (Hamamatsu Photonics K.K., Hamamatsu, Japan). Progressive improvement of clinical conditions was assessed both by patients' self evaluation and by objective clinical follow-up based on: (1) PDE lymphography, (2) tomography of the pubic area, (3) recovery of the soft consistency of the scrotal tissue, (4) recovery of the scrotal skin normochromic aspect, (5) absence of pain, and (6) disappearance of edema with evident reduction of the scrotal and penile dimensions and normal palpability of the testis. The present study shows that lymphovenous anastomosis is a valuable method of resolving the edematous condition. The indocyanine green approach for lymphangiography is a very supportive method during follow-up because, with the least invasive approach, it is possible to ascertain the complete patency of the anastomosis, to confirm its localization, and to assess its lymphatic drainage.