Near-infrared Fluorescence Lymphatic Imaging Research Articles

Association Between Symptom Burden and Early Lymphatic Abnormalities After Regional Nodal Irradiation for Breast Cancer

Background: Dermal backflow visualized on near-infrared fluorescence lymphatic imaging (NIRFLI) signals preclinical lymphedema that precedes the development of volumetrically-defined lymphedema. We sought to evaluate whether dermal backflow correlates with patient-reported lymphedema outcomes (PRLO) surveys in breast cancer patients treated with regional nodal irradiation (RNI). Methods and Materials: Breast cancer patients planned for axillary dissection and RNI prospectively underwent perometry, NIRFLI, and PRLOs (the Lymphedema Symptom Intensity and Distress Survey (LSIDS) and QuickDash) at baseline, after surgery, and at 6, 12, and 18 months following radiation. Clinical lymphedema was defined as an arm volume increase ≥ 5% over baseline. Trends over time were assessed using ANOVA testing. The association between survey responses and both dermal backflow and lymphedema was assessed using a linear mixed-effects model. Results: Sixty participants completed at least two sets of measurements and surveys and were eligible for analysis. Fifty-four percent of patients had cT3-T4 disease, 53% cN3 disease, and 75% had a BMI >25. Dermal backflow and clinical lymphedema increased from 10% to 85% and from 0% to 40%, respectively, from baseline to 18mo. In the adjusted model, soft tissue sensation, neurologic sensation, and functional LSIDS subscale scores were associated with presence of dermal backflow (all p<0.05). Both dermal backflow and lymphedema were associated with Quickdash score (p<0.05). Conclusion: In this high-risk cohort, we found highly prevalent early signs of lymphedema, with increased symptom burden from baseline. Presence of dermal backflow correlated with PRLO measures, highlighting a potential NIRFLI use to identify patients for early intervention trials following RNI.

Imaging peripheral lymphatic dysfunction in chronic conditions.

The lymphatics play important roles in chronic diseases/conditions that comprise the bulk of healthcare worldwide. Yet the ability to routinely image and diagnose lymphatic dysfunction, using commonly available clinical imaging modalities, has been lacking and as a result, the development of effective treatment strategies suffers. Nearly two decades ago, investigational near-infrared fluorescence lymphatic imaging and ICG lymphography were developed as routine diagnostic for clinically evaluating, quantifying, and treating lymphatic dysfunction in cancer-related and primary lymphedema, chronic venous disease, and more recently, autoimmune and neurodegenerative disorders. In this review, we provide an overview of what these non-invasive technologies have taught us about lymphatic (dys) function and anatomy in human studies and in corollary animal studies of human disease. We summarize by commenting on new impactful clinical frontiers in lymphatic science that remain to be facilitated by imaging.

Prediction of breast cancer-related lymphedema by dermal backflow detected with near-infrared fluorescence lymphatic imaging

PurposeMild breast cancer-related lymphedema (BCRL) is clinically diagnosed as a 5%–10% increase in arm volume, typically measured no earlier than 3–6 months after locoregional treatment. Early BCRL treatment is associated with better outcomes, yet amid increasing evidence that lymphedema exists in a latent form, treatment is typically delayed until arm swelling is obvious. In this study, we investigated whether near-infrared fluorescence lymphatic imaging (NIRF-LI) surveillance could characterize early onset of peripheral lymphatic dysfunction as a predictor of BCRL.MethodsIn a prospective, longitudinal cohort/observational study (NCT02949726), subjects with locally advanced breast cancer who received axillary lymph node dissection and regional nodal radiotherapy (RT) were followed serially, between 2016 and 2021, before surgery, 4–8 weeks after surgery, and 6, 12, and 18 months after RT. Arm volume was measured by perometry, and lymphatic (dys) function was assessed by NIRF-LI.ResultsBy 18 months after RT, 30 of 42 study subjects (71%) developed mild–moderate BCRL (i.e., ≥ 5% arm swelling relative to baseline), all manifested by “dermal backflow” of lymph into lymphatic capillaries or interstitial spaces. Dermal backflow had an 83% positive predictive value and 86% negative predictive value for BCRL, with a sensitivity of 97%, specificity of 50%, accuracy of 83%, positive likelihood ratio of 1.93, negative likelihood ratio of 0.07, and odds ratio of 29.00. Dermal backflow appeared on average 8.3 months, but up to 23 months, before the onset of mild BCRL.ConclusionBCRL can be predicted by dermal backflow, which often appears months before arm swelling, enabling early treatment before the onset of edema and irreversible tissue changes.

Lymphatic function and anatomy in early stages of lipedema.

ObjectiveLipedema is an inflammatory subcutaneous adipose tissue disease that develops in women and may progress to lipolymphedema, a condition similar to lymphedema, in which lymphatic dysfunction results in irresolvable edema. Because it has been shown that dilated lymphatic vessels, impaired pumping, and dermal backflow are associated with presymptomatic, cancer‐acquired lymphedema, this study sought to understand whether these abnormal lymphatic characteristics also characterize early stages of lipedema prior to lipolymphedema development.MethodsIn a pilot study of 20 individuals with Stage I or II lipedema who had not progressed to lipolymphedema, lymphatic vessel anatomy and function in upper and lower extremities were assessed by near‐infrared fluorescence lymphatic imaging and compared with that of a control population of similar age and BMI.ResultsThese studies showed that, although lower extremity lymphatic vessels were dilated and showed intravascular pooling, the propulsion rates significantly exceeded those of control individuals. Upper extremity lymphatics of individuals with lipedema were unremarkable. In contrast to individuals with lymphedema, individuals with Stage I and II lipedema did not exhibit dermal backflow.ConclusionsThese results suggest that, despite the confusion in the diagnoses between lymphedema and lipedema, their etiologies differ, with lipedema associated with lymphatic vessel dilation but not lymphatic dysfunction.

Dermal Backflow, Detected by Near-infrared Fluorescence Lymphatic Imaging, Is an Early Prognostic Marker of Breast Cancer-related Lymphedema

Breast cancer-related lymphedema (BCRL) is a complication for millions of patients receiving chemotherapy, axillary lymph node dissection (ALND), and radiation therapy (RTx). Ipsilateral arm swelling of 5% to 10% over baseline, at least 3 months after RTx, is commonly used as a BCRL diagnostic, yet this criteria may only be realized after significant, permanent, lymphatic damage has occurred. As timely complete decongestive treatment has been shown by others to stall or even prevent BCRL, “catching it early” could optimize patient outcomes. We sought to evaluate whether longitudinal near-infrared fluorescence lymphatic imaging (NIRF-LI) of lymphatic dysfunction provides an early predictor of BCRL in advanced breast cancer patient undergoing ALND and RTx. In an ongoing clinical study (NCT02949726), patients with breast cancer were imaged before and after ALND, as well as at 6, 12, and 18 months after RTx, NIRF-LI to visualize dysfunctional lymphatics. Perometer readings of arm volumes were recorded at each imaging session to provide objective diagnosis of BCRL from arm swelling of >5% at or after 6 months after RTx. Perometer readings were compared to pretreatment baseline measurements. Dermal backflow, an NIRF-LI pattern indicating lymph that either fails to enter primary lymphatics and progress to collector vessels, or counterfluxes from collector vessels, appeared in 23 out of 24 women thus far diagnosed with BCRL at time of this report (August 27, 2021). Dermal backflow occurred at the time of diagnosis in 39% of patients, or prior to BCRL diagnosis (mean, 10.4 months; range, 6-25.5 months) in the remaining 61% patients. Of all BCRL diagnoses, 34% were diagnosed at 6 months after RTx. Prior to 6 months after RTx, dermal backflow, but not >5% arm volume increases, were predictive of BCRL. One patient taking biologics for treatment of previously diagnosed rheumatoid arthritis was diagnosed with BCRL prior to appearance of dermal backflow. Another patient developed dermal backflow at study end point and thus, could have developed BCRL beyond the study end point. From a total of 32 patients who have completed the study, NIRF-LI dermal backflow had a specificity and sensitivity of 89% and 96% and an overall accuracy for predicting or detecting BCRL of 97%. Preliminary results show that longitudinal screening of patients with breast cancer with NIRF-LI enables earlier diagnosis of BCRL that could enable optimized outcomes, healthcare cost savings, and improved quality of life for breast cancer survivors. NIRF-LI screening during the first six months after RTx could detect those patients developing lymphatic dysfunction before onset of arm swelling can be used as a benchmark to prescribe complete decongestive treatment.

Abstract P4-11-18: Arm lymphatic pulsing changes after mastectomy or breast-conserving surgery with axillary lymph node dissection, detected with near-infrared fluorescence lymphatic imaging

Abstract Introduction: Axillary lymph node dissection (ALND) that accompanies mastectomy or breast-conserving surgery is assumed to disrupt arm lymphatic fluid pumping that normally flows in a one-way, distal-to-proximal path to transit cellular waste, immune cells, and large molecules to the thorax. Any resulting stagnation of lymph is surmised to drive the development of lymphedema (LE), with potential lifelong, detrimental effects on quality of life for breast cancer survivors, yet the majority of breast cancer survivors receiving ALND never encounter LE. To date, no objective before-and-after-ALND lymphatic pumping data has been published. Methods: In a prospective, ongoing, longitudinal clinical study (NCT02949726) of breast cancer patients undergoing neoadjuvant chemotherapy, axillary lymph node dissection (ALND) with mastectomy or breast-conserving surgery, and radiation treatment (RT), we used near-infrared fluorescence lymphatic imaging (NIRF-LI) to observe changes in arm lymphatics anatomy and pulsing. NIRF-LI, using a custom-built imaging system, with indocyanine green (ICG) contrast, allows “see through the skin” visualization of arm lymph pumping through lymphatic vessels, and captured videos of 58 locally advanced breast cancer patients before and approximately four weeks after mastectomy or breast-conserving surgery with ALND. Lymphatic pumping frequencies (pulses per minute) were determined from fluorescence intensity fluctuations through regions of interest (ROIs) along lymphatic vessels, quantitated with ImageJ (NIH) free software. Ipsilateral and contralateral arm dorsal, ventral, and axillary-feeding (ventral upper arm) vessel pulsing was classified as 1) static or improved to normal range (improved), or 2) transitioning to abnormal ranges (worsened) after surgery. The number of vessels in each category were tallied and reported herein. Results: After ALND, arm lymphatic pulsing frequencies improved or worsened as shown in Table 1. Conclusions: NIRF-LI allowed objective quantitation of arm lymphatic pumping frequencies captured before and after ALND accompanying mastectomy or breast-conserving surgery for breast cancer. Pulsing frequencies in detectable vessels improved in more axilla-feeding vessels, surprisingly, but worsened or did not change in more ipsilateral and ventral vessels, on both ipsilateral and contralateral sides. While cancer surgery with ALND may be associated with increased risk of BCRL, other factors, such as neoadjuvant chemotherapy, cancer severity, and radiation treatment may contribute to LE etiology. Table 1.Anatomical position (arm)# of Vessels Improved# of Vessels WorsenedIpsilateral dorsal6499Ipsilateral ventral73107Ipsilateral axilla-feeding5626Contralateral dorsal97112Contralateral ventral8988Contralateral axilla-feeding10323 Citation Format: Melissa B Aldrich, Meghan E McWain, Wenyaw Chan, John C Rasmussen, Sarah DeSnyder, Eva M Sevick-Muraca, Simona F Shaitelman. Arm lymphatic pulsing changes after mastectomy or breast-conserving surgery with axillary lymph node dissection, detected with near-infrared fluorescence lymphatic imaging [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P4-11-18.

Abstract P1-24-06: Risk factor modeled microenvironment effects lymphatics activity and IBC invasiveness and progression

Abstract Background. Lymphovascular invasion (LVI) and breast tumor emboli within dermal and breast lymphatic vessels are prognostic for metastatic spread and poor outcomes, and are abundant in Inflammatory breast cancer (IBC). IBC is an aggressive breast cancer that presents suddenly with breast swelling and redness due to tumor emboli in lymphatics. Lack of breast-feeding and obesity are IBC risk factors. We sought to demonstrate the combinatorial effects of a high-fat diet and nursing on lymphatic function and compare these to IBC tumor induced changes in lymphatic function. We hypothesize that risk factors for aggressive breast cancer may alter lymphatic function in the normal gland prior to tumor initiation. Methods. Following two rounds of pregnancy in 20 multiparous SCID Beige immunocompromised mice, half of the mice were force weaned while half nursed pups. Prior to forced weaning, half of each of these groups were fed a high fat diet (HFD: 60 Kcal %, N = 10) while the other half received a low-fat diet (LFD: 10 Kcal %, N = 10). Consecutive dynamic near-infrared fluorescence (NIRF) lymphatic imaging was performed at 6-7 months (covid interruption) and 14 months after initiating the diet by injecting a near-IR fluorophore into the mammary fatpad and recording lymphatic pulsing over 8 minutes using V++. Matlab and ImageJ were used to quantify pulsing rates on the ventral lymphatics in each animal. Fatpads were subsequently inoculated with SUM149 IBC cells and imaging was repeated 16 months post diet initiation. Lymphatic imaging over time by HFD vs LFD was further studied in nulliparous animals. Tissues were collected for further analyses. ResultsData analysis prior to tumor injection, demonstrated lymphatic pulsing (pulses/4 minutes) increased over time in HFD force weaned (HFFW) and HFD nursing (HFN) animals only (65.5 vs 72.6, P=0.059; 60.1 vs 76.6, P=0.0099, respectively). Comparing HFFW and HFN to matched LFD groups (LFFW and LFN), at 14 weeks HFD was associated with increased pumping after forced weaning (62.3 vs. 72.6, P=0.074), and nursing (62.5 vs 76.6, P=0.0023). There was an increase in pulsing after tumor initiation (16 months after initiation of diet) in all groups (80.1, 84.1, 83.2, 82.4, P &amp;gt; 0.05 all comparisons to initial timepoint). In a separate experiment examining HFD (N=5) vs LFD (N=5) in nulliparous mice, lymphatic contractile activity increased in all animals over. time, average ventral lymphatic contractile frequency for LFD and HFD at week 8,11 and 14 weeks after diet initiation were 5, 8.64, 15.9 pumps/4 mins vs 11.8, 18.5, 28.2 pumps/4 mins, (P = 0.01, 0.05, and 0.0005 respectively). ConclusionsHFD increased lymphatic pulsing rate over time to a significantly greater extent than LFD continuing over 14 months independent of reproductive and nursing status. Tumor initiation prompted further increased pulsing rates beyond that observed after HFD across all groups. The magnitude of the effect of HFD on lymphatic pulsing approached the rate after tumor initiation, while reproductive variables did not impact lymphatic pulsing. Further studies are warranted to demonstrate the relationship if any between lymphatic pumping pre-initiation and LVI after tumor initiation and examine the role of intervention on reducing LVI. Citation Format: Wintana Balema, Janelle Morton, Richard Larson, Fred C Velasquez, Eva Sevick-Muraca, Wendy A Woodward. Risk factor modeled microenvironment effects lymphatics activity and IBC invasiveness and progression [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-24-06.

Prediction of Breast Cancer-Related Lymphedema by Dermal Backflow Detected With Near-Infrared Fluorescence Lymphatic Imaging: Results of a Prospective, Longitudinal Cohort Study

Prediction of Breast Cancer-Related Lymphedema by Dermal Backflow Detected With Near-Infrared Fluorescence Lymphatic Imaging: Results of a Prospective, Longitudinal Cohort Study

Lymphatic Dissemination and Axillary Web Syndrome in Primary Cutaneous Tuberculosis Secondary to Needlestick Injury.

Cutaneous tuberculosis secondary to skin inoculation of Mycobacterium tuberculosis is uncommon but it can occur in the health care settings. Herein, we report an unusual case of primary cutaneous tuberculosis of the thumb following a needlestick injury. The infection progressed with a necrotic granuloma, lymphatic dysfunction as visualized by near-infrared fluorescence lymphatic imaging, and the development of an axillary web syndrome.

Multimodality lymphatic imaging of postoperative chylothorax in an infant with Noonan syndrome: a case report

BackgroundChylothorax is a rare complication of pediatric cardiac operations that occurs more frequently in children with Noonan syndrome, a genetic disorder associated with cardiac defects and lymphatic anomalies.Case presentationWe report a case of postoperative chylothorax in a 6-month-old infant with Noonan syndrome where multimodality lymphatic imaging guided management was followed. Drainage patterns of the lymphatic capillaries in the lower and upper extremities were visualized during near-infrared fluorescence lymphatic imaging (NIRFLI). Dynamic magnetic resonance lymphangiography (MRL) further identified the site of leakage in the thoracic duct and subsequently guided surgical intervention.ConclusionsApplication of multimodality imaging allows for greater individualization of treatment and should be considered in patients with complex cases such as those with syndromes associated with a higher incidence of chylothorax. IRB Number: HSC-MS-13–0754, December 10, 2013

Degradation of lymphatic anatomy and function in early venous insufficiency

ObjectiveWe used near-infrared fluorescence lymphatic imaging in a pilot study to assess the lymphatics in preulcerative (C2-C4) venous insufficiency and determine whether involvement and/or degradation of lymphatic anatomy or function could play a role in the progression of chronic venous insufficiency. We also explored the role of lymphatics in early peripheral arterial disease. MethodsAfter informed consent and intradermal injections of indocyanine green for rapid lymphatic uptake, near-infrared fluorescence lymphatic imaging was used to assess the lymphatic anatomic structure and quantify the lymphatic propulsion rates in subjects with early venous insufficiency. The anatomic observations included interstitial backflow, characterized by the abnormal spreading of indocyanine green from the injection site primarily into the surrounding interstitial tissues; dermal backflow, characterized by the retrograde movement of dye-laden lymph from collecting lymphatics into the lymphatic capillaries; and lymphatic vessel segmentation and dilation. ResultsTen subjects with venous insufficiency were enrolled, resulting in two legs with C2 disease, nine legs with C3 disease, eight legs with C4 disease, and one leg with C5 disease. Interstitial and/or dermal backflow were observed in 25%, 33%, and 41% of the injection sites in each limb with C2, C3, and C4 disease, respectively. Distinct vessel segmentation and dilation were observed in limbs with a C3 and higher classification, and dermal backflow proximal to the injection sites was observed in two legs with C4 disease and in the inguinal region of the C5 study subject. The overall average lymph propulsion rates were 1.3 ± 0.4, 1.2 ± 0.7, and 0.8 ± 0.5 contractile events/min for limbs with C2, C3, and C4 disease, respectively. One subject with peripheral arterial disease, who had previously undergone bypass surgery, presented with extensive dermal backflow and lymphatic reflux. ConclusionsNear-infrared fluorescence lymphatic imaging demonstrated that, compared with normal health subjects, the lymphatic anatomy and contractile function generally degrade with the severity of venous insufficiency. Lymphatic abnormalities mimic those in early cancer-acquired lymphedema subjects, as previously observed by us and others. Additional studies are needed to decipher the relationship, including any causality, between lymphatic dysfunction and peripheral vascular disease and venous insufficiency.

The Development and Treatment of Lymphatic Dysfunction in Cancer Patients and Survivors.

Breast-cancer-acquired lymphedema is routinely diagnosed from the appearance of irreversible swelling that occurs as a result of lymphatic dysfunction. Yet in head and neck cancer survivors, lymphatic dysfunction may not always result in clinically overt swelling, but instead contribute to debilitating functional outcomes. In this review, we describe how cancer metastasis, lymph node dissection, and radiation therapy alter lymphatic function, as visualized by near-infrared fluorescence lymphatic imaging. Using custom gallium arsenide (GaAs)-intensified systems capable of detecting trace amounts of indocyanine green administered repeatedly as lymphatic contrast for longitudinal clinical imaging, we show that lymphatic dysfunction occurs with cancer progression and treatment and is an early, sub-clinical indicator of cancer-acquired lymphedema. We show that early treatment of lymphedema can restore lymphatic function in breast cancer and head and neck cancer patients and survivors. The compilation of these studies provides insights to the critical role that the lymphatics and the immune system play in the etiology of lymphedema and associated co-morbidities.

Assessing lymphatic route of CSF outflow and peripheral lymphatic contractile activity during head-down tilt using near-infrared fluorescence imaging.

Evidence overwhelmingly suggests that the lymphatics play a critical role in the clearance of cerebrospinal fluid (CSF) from the cranial space. Impairment of CSF outflow into the lymphatics is associated with a number of pathological conditions including spaceflight‐associated neuro‐ocular syndrome (SANS), a problem that limits long‐duration spaceflight. We used near‐infrared fluorescence lymphatic imaging (NIRFLI) to dynamically visualize the deep lymphatic drainage pathways shared by CSF outflow and disrupted during head‐down tilt (HDT), a method used to mimic the cephalad fluid shift that occurs in microgravity. After validating CSF clearance into the lymph nodes of the neck in swine, a pilot study was conducted in human volunteers to evaluate the effect of gravity on the flow of lymph through these deep cervical lymphatics. Injected into the palatine tonsils, ICG was imaged draining into deep jugular lymphatic vessels and subsequent cervical lymph nodes. NIRFLI was performed under HDT, sitting, and supine positions. NIRFLI shows that lymphatic drainage through pathways shared by CSF outflow are dependent upon gravity and are impaired under short‐term HDT. In addition, lymphatic contractile rates were evaluated from NIRFLI following intradermal ICG injections of the lower extremities. Lymphatic contractile activity in the legs was slowed in the gravity neutral, supine position, but increased under the influence of gravity regardless of whether its force direction opposed (sitting) or favored (HDT) lymphatic flow toward the heart. These studies evidence the role of a lymphatic contribution in SANS.

Radiation Dose-Dependent Changes in Lymphatic Remodeling

Postoperative radiation therapy (RT) delivered to lymphatics is associated with an increased risk of developing lymphedema. Reported effects of RT on lymphatic vessels have varied, however, possibly because of the use of different animal models with varying surgery and radiation schedules and the inability to directly and longitudinally image lymphatics invivo. Here we report, using noninvasive imaging, changes in lymphatic remodeling and function in response to surgery and RT in a mouse model. Popliteal lymphadenectomy in mice preceded single-dose gamma irradiation of the lower extremity at a single dose of 0, 20, or 40 Gy. The right hind limb of intact mice was also radiated with 4 fractions (4 × 5 Gy). Near-infrared fluorescence lymphatic imaging with indocyanine green was performed over 6 months to monitor lymphatic vessel remodeling. Postoperative mice treated with 20 Gy showed transient changes in lymphatic drainage, exacerbated vessel remodeling including qualitative vessel dilation and abnormal indocyanine green pooling from week 1 to 2, and initiation of restoration of lymphatic vessels, although dermal backflow was occasionally observed. Mice treated with 40 Gy showed steadily increasing lymphatic impairment until week 3 and extravasation of dye and dermal backflow in weeks 4 to 25. The ankles of mice treated with 40 Gy were significantly swollen from weeks 2 to 4 as compared with mice treated with 0 Gy or 20 Gy. Mice that received fractionated RT exhibited lymphatic vessel remodeling similar to remodeling that occurred when a single 20 Gy dose was given; however, dermal backflow did not resolve as it did in the case of a single 20 Gy dose. The degree of nonreversing lymphatic damage seen in our mouse model was dependent on RT dose. Our results suggest that near-infrared fluorescence lymphatic imaging detection of early lymphatic changes can be used to predict development of lymphedema in patients with cancer.

Imaging the Lymphatic Response to Manual Lymphatic Drainage and Pneumatic Compression Devices

Manual lymphatic drainage (MLD), as a component of complete decongestive therapy, has formed the basis of the initial treatment for lymphedema (LED), and pneumatic compression (PC) has been used in the maintenance phase (at-home treatment). The physiologic mechanism, however, of methods to promote lymph drainage for both MLD and PC has not been rigorously established. Recent developments in near-infrared fluorescence lymphatic imaging (NIRFLI) have enabled the visualization of the lymphatic response to these therapies nearly in real time and provide opportunities to assess the physiologic impact of these manual interventions. Herein we summarize the results of seven studies, published and unpublished, assessing the acute and longitudinal impact of MLD or PC therapy in patients with phlebolymphedema or standard arm, leg, or head and neck LED. After informed consent and under Food and Drug Administration-approved investigational new drugs for off-label administration of indocyanine green (ICG) as an imaging agent for NIRFLI, we visualized lymphatic anatomy and contractile pumping activity in study participants. Patients received intradermal injections of ICG distal to the area of vascular interest, typically in the hands and feet. Imaging was performed by illuminating the skin with near-infrared light and collecting the fluorescent light emanating from the ICG-laden lymph. Whereas imaging times varied between each study, imaging was conducted immediately before and after treatment and, when possible, during treatment. In one study, NIRFLI was also performed before and after 2 weeks of PC therapy in patients with head and neck LED. Images were assessed for changes in lymphatic uptake and contractile pumping. Overall 69 patients, 51 affected and 18 control, undergoing MLD or PC therapy were imaged. The first study of 10 LED and 12 control patients showed a 23% and 28% increase in lymph velocity and a 9% and 23% reduction in propulsion period in symptomatic and control limbs, respectively, in response to MLD. Other NIRFLI studies demonstrated enhanced lymphatic uptake after PC therapy in control patients and patients diagnosed with phlebolymphedema or standard LED. One study, using a clear PC device, demonstrated the ability to image the statistically significant improvement in lymphatic contractile propulsion during and after PC therapy. A recent unpublished study of 10 patients with head and neck LED demonstrated enhanced lymphatic uptake in all patients and a reduction of abnormal lymphatic anatomy in 75% of patients after 2 weeks of daily at-home PC therapy. NIRFLI enables the assessment of manual lymphatic interventions, demonstrating enhanced lymphatic uptake and improved lymphatic contractile pumping in response to MLD and PC therapy in patients with LED.

Head and Neck Lymphedema: Treatment Response to Single and Multiple Sessions of Advanced Pneumatic Compression Therapy.

Ten head and neck cancer survivors diagnosed with head and neck lymphedema (HNL) were imaged using near-infrared fluorescence lymphatic imaging (NIRFLI) prior to and immediately after an initial advance pneumatic compression device treatment and again after 2 weeks of daily at-home use. Images assessed the impact of pneumatic compression therapy on lymphatic drainage. Facial composite measurement scores assessed reduction/increase in external swelling, and survey results were obtained. After a single pneumatic compression treatment, NIRFLI showed enhanced lymphatic uptake and drainage in all subjects. After 2 weeks of daily treatment, areas of dermal backflow disappeared or were reduced in 6 of 8 subjects presenting with backflow. In general, reductions in facial composite measurement scores tracked with reductions in backflow and subject-reported improvements; however, studies are needed to determine whether longer treatment durations can be impactful and whether advanced pneumatic compression can be used to ameliorate backflow characteristic of HNL.

Near-infrared fluorescence lymphatic imaging in vascular endothelial growth factor-C overexpressing murine melanoma.

In this study we employ a near-infrared fluorescence lymphatic imaging (NIRFLI) technique to longitudinally image spatial and temporal changes in the lymphatics in mice bearing vascular endothelial growth factor (VEGF)-C overexpressing B16F10 (VEGF-C-B16F10) or mock-transduced B16F10 (mock-B16F10) melanoma tumors. Our NIRFLI data show that ICG-laden lymph accumulates into a VEGF-C-B16F10 tumor compared to mock-B16F10 at 3 days post implantation, presumably due to increased lymphatic vessel permeability. Quantification shows a significantly greater percentage of ICG-perfused area in VEGF-C-B16F10 (7.6 ± 2) as compared to MOCK-B16F10 (1 ± 0.5; p = 0.02), which is also confirmed by quantification of the lymphatic leakage of evans blue dye (optical density at 610nm; VEGF-C-B16F10, 10.5 ± 2; mock-B16F10, 5.1 ± 0.5; p = 0.009); thereafter, lymphatic leakage is visualized only in the peritumoral region. Our imaging data also show that anti-VEGF-C treatment in VEGF-C-B16F10 restores normal lymphatic vessel integrity and reduces dye extravasation. Because NIRFLI technology can be used to non-invasively detect lymphatic changes associated with cancer, it may provide a new diagnostic to assess the lack of lymphatic vessel integrity that promotes lymphovascular invasion and to assess therapies that could arrest invasion through normalization of the lymphatic vasculature.

How is lymphofluoroscopy mapping altering lymphoedema management?

Lymphoedema management has evolved over many decades, but the core components of treatment remain largely unaltered, such as skin care, compression and self-lymphatic drainage. Near-infrared fluorescence lymphatic imaging (NIRFLI) offers an opportunity to enhance patient outcomes by evaluating and increasing the effectiveness of these treatment options. This is relevant when we consider the impact of this chronic condition and its endemic proportions ( Mortimer, 2014 ), while Moffatt et al (2017) suggests it is one of the biggest health risks in the Western world, due to the multiple causes, such as cancer, obesity and as a complication of an ageing population. The impact of the condition can be reduced through early identification and the risk-reduction strategies that NIRFLI can offer through greater understanding of its chronicity. The use of NIRFLI has also led to the development of a new manual lymphatic drainage technique to assist in the management of lymphoedema ( Belgrado et al, 2016 ). The aim of this article is to introduce and describe NIRFLI and its use within lymphoedema management. It will discuss use with early detection of lymphoedema and expand further, focusing on its use within the management of lymphoedema.

Effect of pneumatic compression therapy on lymph movement in lymphedema-affected extremities, as assessed by near-infrared fluorescence lymphatic imaging.

Previous studies have shown cost effectiveness and quality-of-life benefit of pneumatic compression therapy (PCT) for lymphedema. Insurers, such as the Centers for Medicare/Medicaid (CMS), however, desire visual proof that PCT moves lymph. Near-infrared fluorescence lymphatic imaging (NIRFLI) was used to visualize lymphatic anatomy and function in four subjects with primary and cancer treatment-related lymphedema (LE) of the lower extremities before, during, and after pneumatic compression therapy (PCT). Optically transparent and windowed PCT garments allowed visualization of lymph movement during single, one-hour PCT treatment sessions. Visualization revealed significant extravascular and lymphatic vascular movement of intradermally injected dye in all subjects. In one subject with sufficient patent lymphatic vessels to allow quantification of lymph pumping velocities and frequencies, these values were significantly increased during and after PCT as compared to pre-treatment values. Lymphatic contractile activity in patent lymphatic vessels occurred in concert with the sequential cycling of PCT. Direct visualization revealed increased lymphatic function, during and after PCT therapy, in all lymphedema-affected extremities. Further studies are warranted to assess the effects of PCT pressure and sequences on lymph uptake and movement.

Enhancing lymphoedema patients' learning through education.

British Journal of NursingVol. 26, No. 4 Clinical FocusEnhancing lymphoedema patients' learning through educationJane WiggJane WiggSearch for more papers by this authorJane WiggPublished Online:23 Feb 2017https://doi.org/10.12968/bjon.2017.26.4.204AboutSectionsView articleView Full TextPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareShare onFacebookTwitterLinked InEmail View article References Arndt MJ, Underwood B (1990) Learning style theory and patient education. J Contin Educ Nurs 21(1): 28–31 Medline, Google ScholarBelgrado JP, Vandermeeren L, Vankerckhove S et al. (2016) Near-infrared fluorescence lymphatic imaging to reconsider occlusion pressure of superficial lymphatic collectors in upper extremities of healthy volunteers. Lymphat Res Biol 14(2): 70–7. https://doi.org/https://dx.doi.org/10.1089/lrb.2015.0040 Crossref, Medline, Google ScholarBenner P (1982) From novice to expert. Am J Nurs 82(3): 402–7 Medline, Google ScholarFetzer A, Fetzer S (2015) Early lipoedema diagnosis and the RCGP e-learning course. Br J Community Nurs 20(suppl 4): S22–8. https://doi.org/https://dx.doi.org/10.12968/bjcn.2015.20.Sup4.S22. Link, Google ScholarHibbard J, Gilburt H (2014) Supporting People to Manage Their Health: An Introduction to Patient Activation. The King's Fund, London Google ScholarHoney P, Mumford A (1986) The Manual of Learning Styles. P Honey, Maidenhead Google ScholarMason VL, Upton D, White R (2008) The psychosocial impact of primary lymphoedema. Journal of Lymphoedema 3(2): 50–6 Google ScholarNational Institute for Health and Care Excellence (2012) Patient experience in adult NHS services: improving the experience of care for people using adult and NHS services. Clinical guideline 138. http://tinyurl.com/j7w2njl (accessed 25 January 2017) Google ScholarWigg J (2012) Supervised self-management of lower limb swelling using FarrowWrap. British J Community Nurs 17(4): S22-29. https://doi.org/https://dx.doi.org/10.12968/bjcn.2012.17.Sup4.S22 Link, Google ScholarWigg J (2009) A case for specialist practice. Journal of Lymphoedema 4(1): 72–8 Google Scholar FiguresReferencesRelatedDetailsCited byEmpowering patient self-management through tailored compression garment regimensJeanne Everett, Sue Lawrance, Natalie Phillips8 October 2020 | British Journal of Community Nursing, Vol. 25, No. Sup10Use of Haddenham Venex armsleeve for lymphoedema management in clinical practiceJeanne Everett, Sue Lawrance11 October 2019 | British Journal of Community Nursing, Vol. 24, No. Sup10Critical examination of skin care self-management in lymphoedemaAimee Jones, Mary Woods, Katharine Malhotra11 October 2019 | British Journal of Community Nursing, Vol. 24, No. Sup10How is lymphofluoroscopy mapping altering lymphoedema management?Jane Wigg, Garry Cooper29 September 2017 | British Journal of Community Nursing, Vol. 22, No. Sup10Haddenham easywrap as part of self-management in lymphoedema and lipoedema: The patient perspectiveNatalie Lee, Stacy Pugh, Robin Cooper29 September 2017 | British Journal of Community Nursing, Vol. 22, No. Sup10 23 February 2017Volume 26Issue 4ISSN (print): 0966-0461ISSN (online): 2052-2819 Metrics History Published online 23 February 2017 Published in print 23 February 2017 Information© MA Healthcare LimitedPDF download