Automated analysis of investigational near-infrared fluorescence lymphatic imaging in humans

Zhang, Jingdan; Zhou, S. Kevin; Xiang, Xin; Bautista, Merrick; Niccum, Blake; Dickinson, Gabriel; Tan, I-Chih; Chan, Wenyaw; Sevick‐Muraca, Eva M.; Rasmussen, John C.

doi:10.1364/boe.3.001713

Cited by 10 publications

(6 citation statements)

References 16 publications

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“…Notwithstanding, the resolution is still not sufficient enough to resolve lymphatic capillaries . Some other imaging modalities, for example, positron emission tomography (PET) , ultrasound imaging , photoacoustic imaging , and near‐infrared fluorescence imaging . have also been applied to image the lymphatic vasculature, but they all have a major drawback in that they are invasive in nature due to the need for exogenous contrast agents.…”

Section: Introductionmentioning

confidence: 99%

Lymphatic response to depilation‐induced inflammation in mouse ear assessed with label‐free optical lymphangiography

2015

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Background and Objectives Optical microangiography (OMAG) is a noninvasive technique capable of imaging 3D microvasculature. OMAG-based optical lymphangiography has been developed for 3D visualization of lymphatic vessels without the need for exogenous contrast agents. In this study, we utilize the optical lymphangiography to investigate dynamic changes in lymphatic response within skin tissue to depilation-induced inflammation by using mouse ear as a simple tissue model. Materials and Methods A spectral-domain optical coherence tomography (OCT) system is used in this study to acquire volumetric images of mouse ear. The system operates under the ultrahigh-sensitive OMAG scanning protocol with 5 repetitions for each B frame. An improved adaptive-threshold-based method is proposed to segment lymphatic vessels from OCT microstructure images. Depilation is achieved by placing hair removal lotion on mouse ear pinna for 5 minutes. 3 acquisitions are made before depilation, 3-minute and 30-minute post-depilation, respectively. Results Right after the application of depilation lotion on the skin, we observe that the blind-ended sacs of initial lymphatics are mainly visible in a specific area of the normal tissue. At 5 minutes, more collecting lymphatic vessels start to form, evidenced by their valve structure that only exists in collecting lymphatic vessels. The lymphangiogenesis is almost completed within 8 minutes in the inflammatory tissue. Conclusions Our experimental results demonstrate that the OMAG-based optical lymphangiography has great potential to improve the understanding of lymphatic system in response to various physiological conditions, thus would benefit the development of effective therapeutics.

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Section: Introductionmentioning

confidence: 99%

Lymphatic response to depilation‐induced inflammation in mouse ear assessed with label‐free optical lymphangiography

2015

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“…Additional alterations in lymphoid biology during inflammatory arthritis include increased vascular endothelial growth factor c (VEGF-C)-dependent lymphangiogenesis, especially within the PLN (Zhang et al 2007(Zhang et al , 2011, and diminished lymphatic pulse as determined by near infrared-indocyanine green (NIR-ICG) imaging (Li et al 2013;Zhou et al 2011). While loss of the lymphatic pulse and draining lymph node collapse are now recognized as important biomarkers of flare in RA patients (Manzo et al 2011), progress towards a therapeutic intervention has stalled due to a lack of knowledge regarding the mechanisms that govern these pathological events, and the absence of methods to quantify lymphatic function in humans, which has only recently been achieved (Rasmussen et al 2010;Zhang et al 2012).…”

Section: Introductionmentioning

confidence: 99%

In vivo quantification of lymph viscosity and pressure in lymphatic vessels and draining lymph nodes of arthritic joints in mice

Bouta

Wood

Brown

et al. 2014

The Journal of Physiology

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Key pointsr Previously, it was found that the popliteal lymph node (PLN) enlarges during the pre-arthritic 'expanding' phase, and then 'collapses' with adjacent knee flare and is associated with the loss of the intrinsic lymphatic pulse.r However, the mechanisms responsible are unknown and we therefore developed in vivo methods to measure lymph viscosity, lymphatic pumping pressure (LPP) in the lymphatic vessels afferent to the PLN, and lymph node pressure (LNP).r Multiphoton fluorescence recovery after photobleaching (MP-FRAP) was used to calculate lymph viscosity and speed; no difference was found among mice with wild-type (WT), expanding or collapsed PLN in lymph viscosity, but lymph speed was found to be decreased in mice with collapsed PLN compared to WT and expanding PLN mice.r LPP was measured indirectly by slowly releasing a pressurized cuff occluding ICG fluorescent dye; we found that mice with expanding PLN exhibit a higher LPP compared to WT and mice with collapsed PLN show an extremely low LPP.r Direct measurement of LNP demonstrated a decrease in expanding PLN versus WT pressure, which dramatically increased in collapsed PLN.r The decrease in lymphatic flow and loss of LPP during PLN collapse are consistent with decreased drainage from the joint during arthritic flare, and validate these biomarkers of rheumatoid arthritis progression and possibly other chronic inflammatory conditions Abstract Rheumatoid arthritis (RA) is a chronic inflammatory joint disease with episodic flares. In TNF-Tg mice, a model of inflammatory-erosive arthritis, the popliteal lymph node (PLN) enlarges during the pre-arthritic 'expanding' phase, and then 'collapses' with adjacent knee flare associated with the loss of the intrinsic lymphatic pulse. As the mechanisms responsible are unknown, we developed in vivo methods to quantify lymph viscosity and pressure in mice with wild-type (WT), expanding and collapsed PLN. While no differences in viscosity were detected via multiphoton fluorescence recovery after photobleaching (MP-FRAP) of injected FITC-BSA, a 32.6% decrease in lymph speed was observed in vessels afferent to collapsed PLN (P < 0.05). Direct measurement of intra-lymph node pressure (LNP) demonstrated a decrease in expanding PLN versus WT pressure (3.41 ± 0.43 vs. 6.86 ± 0.56 cmH 2 O; P < 0.01), which dramatically increased to 9.92 ± 1.79 cmH 2 O in collapsed PLN. Lymphatic pumping pressure (LPP), measured indirectly by slowly releasing a pressurized cuff occluding indocyanine green (ICG), demonstrated an increase in vessels afferent to expanding PLN versus WT (18.76 ± 2.34 vs. 11.04 ± 1.47 cmH 2 O; P < 0.01), which dropped to 2.61 ± 0.72 cmH 2 O (P < 0.001) after PLN collapse. Herein, we document the first in vivo measurements of murine lymph viscosity and lymphatic pressure, and provide evidence to support the hypothesis that lymphangiogenesis and lymphatic transport are compensatory mechanisms to prevent synovitis via increased drainage of inflamed joints. Furthermore, the decrease in lymphatic flow and loss of LP...

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“…Images were evaluated for abnormal dermal backflow, in which lymphatic vessels drain distally into the lymphatic capillaries, tortuous lymphatic vessels, and lymphatic contractile dysfunction. [5, 6]…”

Section: Case Reportmentioning

confidence: 99%

Near-infrared fluorescence lymphatic imaging in a patient treated for venous occlusion

Rasmussen

Aldrich

Guilliod

et al. 2015

Journal of Vascular Surgery Cases

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Although lower extremity edema/lymphedema can result from venous and/or lymphatic abnormalities, effective treatment depends upon understanding their relative contributions to the condition. Herein we use near-infrared fluorescence lymphatic imaging in a 16 year-old female diagnosed with unilateral lymphedema of the right leg and previously treated with left iliac vein stenting in an attempt to alleviate lymphedema. The imaging shows that abnormal lymphatic anatomy, rather than venous occlusion, was likely responsible for unilateral swelling.

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Automated analysis of investigational near-infrared fluorescence lymphatic imaging in humans

Cited by 10 publications

References 16 publications

Lymphatic response to depilation‐induced inflammation in mouse ear assessed with label‐free optical lymphangiography

Lymphatic response to depilation‐induced inflammation in mouse ear assessed with label‐free optical lymphangiography

In vivo quantification of lymph viscosity and pressure in lymphatic vessels and draining lymph nodes of arthritic joints in mice

Near-infrared fluorescence lymphatic imaging in a patient treated for venous occlusion

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