Near-infrared fluorescence lymphatic imaging in a patient treated for venous occlusion.
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ABSTRACT:
SUBMITTER: Rasmussen JC
PROVIDER: S-EPMC5356231 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundLymphangiomatosis is a rare disorder of the lymphatic system that can impact the dermis, soft tissue, bone, and viscera and can be characterized by lymphangiomas, swelling, and chylous discharge. Whether disordered lymphangiogenesis in lymphangiomatosis affects the function and anatomy of the entire systemic lymphatic circulation or is localized to specific sites is not fully known.Methods and resultsA 35-year-old Caucasian female diagnosed with whole-body lymphangiomatosis at 2 months of age and who continues to present with progressive disease was imaged with near-infrared fluorescence lymphatic imaging. While the peripheral lymphatics in the extremities appeared largely normal compared to prior studies, we observed tortuous lymphatic vessels, fluorescence drainage from the peripheral lymphatics into lymphangiomas, and extensive dermal lymphatics in the left thigh and inguinal regions where the subject had previously had surgical assaults, potentially indicating defective systemic lymphangiogenesis.ConclusionsFurther research into anatomical and functional lymphatic changes associated with the progression and treatment of lymphangiomatosis could aid in understanding the pathophysiology of the disease as well as point to treatment strategies.
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Project description:While the lymphatic system is increasingly associated with diseases of prevalence, study of these diseases is difficult owing to the paucity of imaging techniques with the sensitivity and temporal resolution to discriminate lymphatic function. Herein, we review the known, pertinent features of the human lymphatic system in health and disease and set the context for a number of emerging studies that use near-infrared fluorescence imaging to non-invasively assess tumor draining lymphatic basins in cancer patients, intraoperatively guide resection of first draining lymph nodes, and to interrogate the difference between normal and aberrant lymphatic structure and function.
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Project description:BackgroundThere are very little scientific data on occlusion pressure for superficial lymphatic collectors. Given its importance in determining the transport capacity of lymphatic vessels, it is crucial to know its value. The novel method of near-infrared fluorescence lymphatic imaging (NIRFLI) can be used to visualize lymphatic flow in real time. The goal of this study was to see if this method could be used to measure the lymphatic occlusion pressure.MethodsWe observed and recorded lymph flow in the upper limb of healthy volunteers through a transparent cuff using near-infrared fluorescence lymphatic imaging. After obtaining a baseline of the lymph flow without pressure inside the cuff, the cuff was inflated by increments of 10 mm Hg starting at 30 mm Hg. A NIRFLI guided manual lymphatic drainage technique named "Fill & Flush Drainage Method" was performed during the measurement to promote lymph flow. Lymphatic occlusion pressure was determined by observing when lymph flow stopped under the cuff.ResultsWe measured the lymphatic occlusion pressure on 30 healthy volunteers (11 men and 19 women). Mean lymphatic occlusion pressure in the upper limb was 86 mm Hg (CI ±3.7 mm Hg, α = 0.5%). No significant differences were found between age groups (p = 0.18), gender (p = 0.12), or limb side (p = 0.85).ConclusionsNIRFLI, a transparent sphygmomanometer cuff and the "Fill and Flush" manual lymphatic drainage method were used to measure the lymphatic occlusion pressure in 30 healthy humans. That combination of these techniques allows the visualization of the lymph flow in real time, while ensuring the continuous filling of the lymph collectors during the measurement session, reducing false negative observations. The measured occlusion pressures are much higher than previously described in the medical literature.
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Project description:We demonstrate the ability to non-invasively and quantitatively image lymphatic architecture and contractile function using dynamic near-infrared (NIR) fluorescence imaging with injection of indocyanine green in normal and transgenic mice. Unlike normal mice, which showed well defined lymphatic drainage patterns and orthograde propagation of contraction waves, we observed tortuous and mispatterned lymphatic vessels and persistent retrograde lymph flow in mice with deficiency in Prox1, a transcription factor essential for lymphatic vascular development. NIR fluorescence imaging provides a method for quantifying lymphatic function for future studies designed to discern differences in lymphatic function in murine models of human lymphatic disease.
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Project description:The relationship between lymphatic and venous malformations in Klippel-Trénaunay syndrome is difficult to assess. Herein the authors describe near-infrared fluorescence lymphatic imaging to assess the lymphatics of a subject with a large port-wine stain and right leg edema. Although lymphatic vessels in the medial, affected knee appeared dilated and perhaps tortuous, no definitive abnormal lymphatic pooling or propulsion was observed. The lymphatics in the affected limb were well defined but less numerous than in the contralateral limb, and active, contractile function was observed in all vessels. As demonstrated, near-infrared fluorescence lymphatic imaging enables the clinical assessment of lymphatics in lymphovenous malformations.
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Project description:PurposeThe aim of this study was to develop and characterize a novel peptide imaging agent for noninvasive near-infrared fluorescence imaging of protein transport by the lymphatics. An imaging agent consisting of a cyclic albumin-binding domain (cABD) peptide, with sequence, Arg-Leu-Ile-Glu-Asp-Ile-Cys-Leu-Pro-Arg-Trp-Gly-Cys-Leu-Trp-Glu-Asp-Asp-Lys, was conjugated to a near-infrared fluorophore, IRDye800CW, allowing for enhanced vascular uptake, retention, and fluorescence imaging.ProcedureCharacterization of the cABD-IRDye800 peptide conjugate was performed using fluorescence spectroscopy to assess optical properties and SDS-PAGE and Biacore binding assays to determine binding affinity and specificity. Fluorescence imaging of normal C57BL/6 mice was conducted to monitor lymphatic uptake and retention.ResultscABD-IRDye800 exhibited approximately six times greater fluorescent yield and greater stability than indocyanine green, an agent previously used in humans to image lymphatic vasculature. The agent exhibited affinity for albumin with IC(50) and Kd in the nanomolar range and demonstrated superior retention characteristics within mouse lymphatics when compared with IRDye800CW.ConclusionscABD-IRDye800 has utility for assessing lymphatic function in mouse models of human lymphatic disease and the potential for use in clinical diagnostic imaging of the lymphatic vasculature.
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Project description:Primary lymphedema in the pediatric population remains poorly diagnosed and misunderstood due to a lack of information on the causation and underlying anatomy of the lymphatic system. Consequently, therapeutic protocols for pediatric patients remain sparse and with little evidence to support them. In an effort to better understand the causation of primary pediatric lymphedema and to better inform clinical care, we report the use of near-infrared fluorescence lymphatic imaging on the extremities of an alert, 21-month-old boy who presented with unilateral right arm and hand lymphedema at birth. The imaging results indicated an intact, apparently normal lymphatic anatomy with no obvious malformation, but with decreased lymphatic contractile function of the affected upper extremity relative to the contralateral and lower extremities. We hypothesized that the lack of contraction of the lymphatic vessels rather than an anatomic malformation was the source of the unilateral extremity swelling, and that compression and manual lymphatic drainage could be effective treatments.
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Project description:ObjectiveTo investigate the feasibility of assessing the efficacy of manual lymphatic drainage (MLD), a method for lymphedema (LE) management, by using near-infrared (NIR) fluorescence imaging.DesignExploratory pilot study.SettingPrimary care unit.ParticipantsSubjects (N=10; age, 18-68y) with a diagnosis of grade I or II LE and 12 healthy control subjects (age, 22-59y).InterventionIndocyanine green (25 ?g in 0.1 mL each) was injected intradermally in bilateral arms or legs of subjects. Diffused excitation light illuminated the limbs, and NIR fluorescence images were collected by using custom-built imaging systems. Subjects received MLD therapy, and imaging was performed pre- and posttherapy.Main outcome measuresApparent lymph velocities and periods between lymphatic propulsion events were computed from fluorescence images. Data collected pre- and post-MLD were compared and evaluated for differences.ResultsBy comparing pre-MLD lymphatic contractile function against post-MLD lymphatic function, results showed that average apparent lymph velocity increased in both the symptomatic (+23%) and asymptomatic (+25%) limbs of subjects with LE and control limbs (+28%) of healthy subjects. The average lymphatic propulsion period decreased in symptomatic (-9%) and asymptomatic (-20%) limbs of subjects with LE, as well as in control limbs (-23%).ConclusionsWe showed that NIR fluorescence imaging could be used to quantify immediate improvement of lymphatic contractile function after MLD.
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Project description:ALFIA (Automated Lymphatic Function Imaging Analysis), an algorithm providing quantitative analysis of investigational near-infrared fluorescence lymphatic images, is described. Images from nine human subjects were analyzed for apparent lymphatic propagation velocities and propulsion periods using manual analysis and ALFIA. While lymphatic propulsion was more easily detected using ALFIA than with manual analysis, statistical analyses indicate no significant difference in the apparent lymphatic velocities although ALFIA tended to calculate longer propulsion periods. With the base ALFIA algorithms validated, further automation can now proceed to provide a clinically relevant analytic tool for quantitatively assessing lymphatic function in humans.
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Project description:Changes in interstitial fluid clearance are implicated in many diseases. Using near-infrared (NIR) imaging with properly sized tracers could enhance our understanding of how venous and lymphatic drainage are involved in disease progression or enhance drug delivery strategies. We investigated multichromatic NIR imaging with multiple tracers to assess in vivo microvascular clearance kinetics and pathways in different tissue spaces. We used a chemically inert IR Dye 800CW (D800) to target venous capillaries and a purified conjugate of IR dye 680RD with 40 kDa PEG (P40D680) to target lymphatic capillaries in vivo. Optical imaging settings were validated and tuned in vitro using tissue phantoms. We investigated multichromatic NIR imaging's utility in two in vivo tissue beds: the mouse tail and rat knee joint. We then tested the ability of the approach to detect interstitial fluid perturbations due to exercise. In an in vitro simulated tissue environment, free dye and PEG mixture allowed for simultaneous detection without interference. In the mouse tail, co-injected NIR tracers cleared from the interstitial space via distinct routes, suggestive of lymphatic and venous uptake mechanisms. In the rat knee, we determined that exercise after injection transiently increased lymphatic drainage as measured by lower normalized intensity immediately after exercise, whereas exercise pre-injection exhibited a transient delay in clearance from the joint. NIR imaging enables simultaneous imaging of lymphatic and venous-mediated fluid clearance with great sensitivity and can be used to measure temporal changes in clearance rates and pathways.
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