Characteristic Indocyanine Green Lymphography Findings in Lower Extremity Lymphedema: The Generation of a Novel Lymphedema Severity Staging System Using Dermal Backflow Patterns

Yamamoto, Takumi; Narushima, Mitsunaga; Doi, Kentaro; Oshima, Akira; Ogata, Fusa; Mihara, Makoto; Koshima, Isao; Mundinger, Gerhard S.

doi:10.1097/prs.0b013e31820cf5df

Cited by 422 publications

(353 citation statements)

References 18 publications

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“…15,16 ICG has also been investigated in patients with breast, gastric, and skin cancer undergoing sentinel lymph node mapping, [17][18][19][20][21][22][23] and evaluation of lymphedema. 24,25 Despite its proven efficacy in these applications, the utility of ICG for broader clinical usage has been limited due to its nonspecific binding to albumin and high-density lipoproteins in plasma. Such binding results in rapid clearance of ICG from blood (with plasma half-life in the order of 2-4 minutes).…”

Section: Introductionmentioning

confidence: 99%

Effects of nanoencapsulation and PEGylation on biodistribution of indocyanine green in healthy mice: quantitative fluorescence imaging and analysis of organs

Bahmani¹,

Lytle²,

Walker³

et al. 2013

IJN

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Near-infrared nanoconstructs present a potentially effective platform for site-specific and deep tissue optical imaging and phototherapy. We have engineered a polymeric nanocapsule composed of polyallylamine hydrochloride (PAH) chains cross-linked with sodium phosphate and doped with indocyanine green (ICG) toward such endeavors. The ICG-doped nanocapsules were coated covalently with polyethylene glycol (5000 daltons) through reductive amination. We administrated the constructs by tail vein injection to healthy mice. To characterize the biodistribution of the constructs, we performed in vivo quantitative fluorescence imaging and subsequently analyzed the various extracted organs. Our results suggest that encapsulation of ICG in these PEGylated constructs is an effective approach to prolong the circulation time of ICG and delay its hepatic accumulation. Increased bioavailability of ICG, due to encapsulation, offers the potential of extending the clinical applications of ICG, which are currently limited due to rapid elimination of ICG from the vasculature. Our results also indicate that PAH and ICG-doped nanocapsules (ICG-NCs) are not cytotoxic at the levels used in this study.

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Section: Introductionmentioning

confidence: 99%

Effects of nanoencapsulation and PEGylation on biodistribution of indocyanine green in healthy mice: quantitative fluorescence imaging and analysis of organs

Bahmani¹,

Lytle²,

Walker³

et al. 2013

IJN

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“…To evaluate the lymphatic vessels in RAMP3−/− mice, we first performed fluorescence lymphography using indocyanine green (ICG), which is used clinically to assess lymphatic function [26]. ICG is rapidly taken up by initial lymphatics and, upon surface illumination with tissue-penetrating near infrared excitation light, the fluorescence emitted by the ICG-laden lymph can be detected with high spatial and temporal resolution, enabling visualization of lymphatic drainage [27].…”

Section: Discussionmentioning

confidence: 99%

Functional differentiation of RAMP2 and RAMP3 in their regulation of the vascular system

Yamauchi

Sakurai

Kamiyoshi

et al. 2014

Journal of Molecular and Cellular Cardiology

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Adrenomedullin (AM) is a vasoactive peptide that possesses various bioactivities. AM receptors are dimers consisting of CLR with one of two accessory proteins, RAMP2 or RAMP3. The functional difference between CLR/RAMP2 and CLR/RAMP3 and the relationship between the two receptors remain unclear. To address these issues, we generated RAMP2 and RAMP3 knockout (−/−) mice and have been studying their physiological activities in the vascular system. AM−/− and RAMP2−/− mice die in utero due to blood vessel abnormalities, which is indicative of their essential roles in vascular development. In contrast, RAMP3−/− mice were born normally without any major abnormalities. In adult RAMP3−/− mice, postnatal angiogenesis was normal, but lymphangiography using indocyanine green (ICG) showed delayed drainage of subcutaneous lymphatic vessels. Moreover, chyle transport by intestinal lymphatics was delayed in RAMP3−/− mice, which also showed more severe interstitial edema than wild-type mice in a tail lymphedema model, with characteristic dilatation of lymphatic capillaries and accumulation of inflammatory cells. In scratch-wound assays, migration of isolated RAMP3−/ − lymphatic endothelial cells was delayed as compared to wild-type cells, and AM administration failed to enhance the re-endothelialization. The delay in re-endothelialization was due to a primary migration defect rather than a decrease in proliferation. These results suggest that RAMP3 regulates drainage through lymphatic vessels, and that the AM-RAMP3 system could be a novel therapeutic target for controlling postoperative lymphedema.

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“…With the use of a CCD camera the light emitted by ICG absorbed in lymph vessels is imaged and lymph fl ow in subcutaneous lymph vessels is detected. In a non-lymphedematous limb a linear pattern of lymph fl ow is a normal fi nding, whereas a splash, stardust or diff use pattern indicates lymphedema [29][30][31]. In secondary lymphedema of the upper extremity, sensitivity and specifi city of the test has been reported to be 100 %, respectively [20].…”

Section: Indocyanine Green (Icg) Fl Uorescence Lymphographymentioning

confidence: 99%

Clinical and diagnostic aspects of lymphedema

Keo

Gretener

Staub

2017

Vasa

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Summary: Lymphedema is a chronic, progressive, and common but often unrecognized condition. The diagnosis of lymphatic disease on clinical grounds alone remains a challenge. Without proper diagnosis, therapy is often delayed, allowing disease progression. There is a need for a practical diagnostic algorithm and its imaging technique to guide clinical decision-making. The aim of this topical review is to provide a practical approach for assessing patients with suspected lymphedema and to give a critical appraisal of currently available imaging modalities that are applied in clinical practice to diagnose and map lymphatic disease.

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Characteristic Indocyanine Green Lymphography Findings in Lower Extremity Lymphedema: The Generation of a Novel Lymphedema Severity Staging System Using Dermal Backflow Patterns

Cited by 422 publications

References 18 publications

Effects of nanoencapsulation and PEGylation on biodistribution of indocyanine green in healthy mice: quantitative fluorescence imaging and analysis of organs

Effects of nanoencapsulation and PEGylation on biodistribution of indocyanine green in healthy mice: quantitative fluorescence imaging and analysis of organs

Functional differentiation of RAMP2 and RAMP3 in their regulation of the vascular system

Clinical and diagnostic aspects of lymphedema

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