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Measurements of Lymph Flow

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Non Invasive Diagnostic Techniques in Clinical Dermatology

Abstract

The lymphatic vasculature is present in nearly every tissue of the body to serve essential functions in fluid homeostasis, immune cell trafficking, and lipid transport, and it has been implicated in the progression of several diseases. This is achieved through the intrinsic contractility of the pumping collecting lymphatics returning fluid up a pressure gradient from the interstitium to the venous circulation. Despite the critical roles that this system performs, very little is known about the lymphatic vasculature in comparison to the blood vasculature, which can be attributed, in part, to the difficulty associated with imaging lymphatic vessels. With the growing interest in studying lymphatic vessels, new techniques are being developed to improve the spatial resolution to visualize small initial lymphatics and increase temporal resolution to capture the dynamic lymphatic pump function responsible for fluid propulsion. In this chapter, we summarize imaging techniques currently used to study lymphatics in vivo, including the two gold standards of lymphatic imaging, lymphoscintigraphy and MRI, as well as PET and CT scanning, ultrasound, and optical imaging techniques. We detail the advantages and limitations of each technique in the context of visualizing lymphatic vessel geometries, quantifying dynamic lymph transport, and identifying sentinel lymph nodes. We also discuss emerging imaging technologies as potential techniques for the future of lymphatic imaging.

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References

  1. Dixon JB (2010) Lymphatic lipid transport: sewer or subway? Trends Endocrinol Metabol 21:480–487

    CAS  Google Scholar 

  2. Levick JR, Michel CC (2010) Microvascular fluid exchange and the revised Starling principle. Cardiovasc Res 87:198–210

    PubMed  CAS  Google Scholar 

  3. Rockson SG (2001) Lymphedema. Am J Med 110:288–295

    PubMed  CAS  Google Scholar 

  4. Rockson SG (2008) Diagnosis and management of lymphatic vascular disease. J Am Coll Cardiol 52:799–806

    PubMed  Google Scholar 

  5. Harvey N et al (2005) Lymphatic vascular defects promoted by Prox1 haploinsufficiency cause adult-onset obesity. Nat Genet 37:1072–1081

    PubMed  CAS  Google Scholar 

  6. Alitalo K, Tammela T, Petrova T (2005) Lymphangiogenesis in development and human disease. Nature 438:946–953

    PubMed  CAS  Google Scholar 

  7. Ji RC (2005) Characteristics of lymphatic endothelial cells in physiological and pathological conditions. Histol Histopathol 20:155–175

    PubMed  CAS  Google Scholar 

  8. Baluk P (2005) Pathogenesis of persistent lymphatic vessel hyperplasia in chronic airway inflammation. J Clin Invest 115:247–257

    PubMed  CAS  Google Scholar 

  9. Foldi M (2003) Foldi’s textbook of lymphology: for physicians and lymphedema therapists. Elsevier GmbH, Munich, Germany

    Google Scholar 

  10. Dixon JB, Moore JE Jr, Cote G, Gashev AA, Zawieja DC (2006) Lymph flow, shear stress, and lymphocyte velocity in rat mesenteric prenodal lymphatics. Microcirculation 13:597–610

    PubMed  Google Scholar 

  11. Zhang F, Niu G, Lu G, Chen X (2010) Preclinical lymphatic imaging. Mol Imaging Biol 13:599–612

    Google Scholar 

  12. Ege GN (1976) Internal mammary lymphoscintigraphy. The rationale, technique, interpretation and clinical application: a review based on 848 cases. Radiology 118:101–107

    PubMed  CAS  Google Scholar 

  13. Veronesi U et al (1997) Sentinel-node biopsy to avoid axillary dissection in breast cancer with clinically negative lymph-nodes. Lancet 349:1864–1867

    PubMed  CAS  Google Scholar 

  14. Weissleder H, Weissleder R (1988) Lymphedema: evaluation of qualitative and quantitative lymphoscintigraphy in 238 patients. Radiology 167:729–735

    PubMed  CAS  Google Scholar 

  15. Wilting J, Becker J, Buttler K, Weich HA (2009) Lymphatics and inflammation. Curr Med Chem 16:4581–4592

    PubMed  CAS  Google Scholar 

  16. Ristimäki A, Narko K, Enholm B, Joukov V, Alitalo K (1998) Proinflammatory cytokines regulate expression of the lymphatic endothelial mitogen vascular endothelial growth factor-C. J Biol Chem 273:8413–8418

    PubMed  Google Scholar 

  17. Saban MR et al (2004) Visualization of lymphatic vessels through NF-kappaB activity. Blood 104:3228–3230

    PubMed  CAS  Google Scholar 

  18. Pepper MS, Tille J-C, Nisato R, Skobe M (2003) Lymphangiogenesis and tumor metastasis. Cell Tissue Res 314:167–177

    PubMed  CAS  Google Scholar 

  19. Sharma R et al (2008) New horizons for imaging lymphatic function. Ann N Y Acad Sci 1131:13–36

    PubMed  CAS  Google Scholar 

  20. Szuba A, Shin WS, Strauss HW, Rockson S (2003) The third circulation: radionuclide lymphoscintigraphy in the evaluation of lymphedema. J Nucl Med 44:43–57

    PubMed  Google Scholar 

  21. Szuba A, Strauss W, Sirsikar SP, Rockson SG (2002) Quantitative radionuclide lymphoscintigraphy predicts outcome of manual lymphatic therapy in breast cancer-related lymphedema of the upper extremity. Nucl Med Commun 23:1171–1175

    PubMed  CAS  Google Scholar 

  22. Weiss M, Baumeister RGH, Hahn K (2002) Post-therapeutic lymphedema: scintigraphy before and after autologous lymph vessel transplantation: 8 years of long-term follow-up. Clin Nucl Med 27:788–792

    PubMed  Google Scholar 

  23. Szuba A et al (2002) Therapeutic lymphangiogenesis with human recombinant VEGF-C. FASEB J 16:1985–1987

    PubMed  CAS  Google Scholar 

  24. Boccardo FM et al (2011) Surgical prevention of arm lymphedema after breast cancer treatment. Ann Surg Oncol 18:2500–2505

    PubMed  Google Scholar 

  25. Kafejian-Haddad AP, Perez JMC, Castiglioni MLV, Miranda Júnior F, de Figueiredo LFP (2006) Lymphscintigraphic evaluation of manual lymphatic drainage for lower extremity lymphedema. Lymphology 39:41–48

    PubMed  CAS  Google Scholar 

  26. Campisi C et al (2006) Diagnosis and management of primary chylous ascites. YMVA 43:1244–1248

    Google Scholar 

  27. Morton DL et al (1992) Technical details of intraoperative lymphatic mapping for early stage melanoma. Arch Surg (Chicago, Ill: 1960) 127:392–399

    CAS  Google Scholar 

  28. Giuliano AE, Kirgan DM, Guenther JM, Morton DL (1994) Lymphatic mapping and sentinel lymphadenectomy for breast cancer. Ann Surg 220:391–398; discussion 398–401

    PubMed  CAS  Google Scholar 

  29. Krag D et al (1998) The sentinel node in breast cancer–a multicenter validation study. N Engl J Med 339:941–946

    PubMed  CAS  Google Scholar 

  30. Czerniecki BJ, Bedrosian I, Faries M, Alavi A (2001) Revolutionary impact of lymphoscintigraphy and intraoperative sentinel node mapping in the clinical practice of oncology. Semin Nucl Med 31:158–164

    PubMed  CAS  Google Scholar 

  31. Nakashima K et al (2010) Preoperative dynamic lymphoscintigraphy predicts sentinel lymph node metastasis in patients with early breast cancer. Breast Cancer 17:17–21

    PubMed  Google Scholar 

  32. Thompson M et al (2007) Axillary reverse mapping (ARM): a new concept to identify and enhance lymphatic preservation. Ann Surg Oncol 14:1890–1895

    PubMed  Google Scholar 

  33. Modi S et al (2007) Human lymphatic pumping measured in healthy and lymphoedematous arms by lymphatic congestion lymphoscintigraphy. J Physiol (Lond) 583:271–285

    CAS  Google Scholar 

  34. Ploeg IMC, Valdés Olmos RA, Kroon BBR, Nieweg OE (2008) The hybrid SPECT/CT as an additional lymphatic mapping tool in patients with breast cancer. World J Surg 32:1930–1934

    PubMed  Google Scholar 

  35. van der Ploeg IMC, Olmos RAV, Kroon BBR, Rutgers EJT, Nieweg OE (2009) The hidden sentinel node and SPECT/CT in breast cancer patients. Eur J Nucl Med Mol Imaging 36:6–11

    PubMed  Google Scholar 

  36. Uren RF (2009) SPECT/CT lymphoscintigraphy to locate the sentinel lymph node in patients with melanoma. Ann Surg Oncol 16:1459–1460

    PubMed  Google Scholar 

  37. Uren RF et al (2011) SPECT/CT scans allow precise anatomical location of sentinel lymph nodes in breast cancer and redefine lymphatic drainage from the breast to the axilla. Breast. doi:10.1016/j.breast.2011.11.007

    Google Scholar 

  38. Schöder H et al (2006) Molecular targeting of the lymphovascular system for imaging and therapy. Cancer Metastasis Rev 25:185–201

    PubMed  Google Scholar 

  39. O’Mahony S, Solanki C (2006) Imaging of lymphatic vessels in breast cancer–related lymphedema: intradermal versus subcutaneous injection of 99mTc-immunoglobulin. Am J

    Google Scholar 

  40. Delbeke D (1999) Oncological applications of FDG PET imaging: brain tumors, colorectal cancer, lymphoma and melanoma. J Nucl Med 40:591–603

    PubMed  CAS  Google Scholar 

  41. Hoffman JM, Gambhir SS (2007) Molecular imaging: the vision and opportunity for radiology in the future. Radiology 244:39–47

    PubMed  Google Scholar 

  42. Veenstra HJ, Vermeeren L, Olmos RAV, Nieweg OE (2012) The additional value of lymphatic mapping with routine SPECT/CT in unselected patients with clinically localized melanoma. Ann Surg Oncol 19:1018–1023

    PubMed  Google Scholar 

  43. Nune SK, Gunda P, Majeti BK, Thallapally PK, Forrest ML (2011) Advances in lymphatic imaging and drug delivery. Adv Drug Deliv Rev 63:876–885

    PubMed  CAS  Google Scholar 

  44. Barrett T, Choyke PL, Kobayashi H (2006) Imaging of the lymphatic system: new horizons. Contrast Media Mol Imaging 1:230–245

    PubMed  CAS  Google Scholar 

  45. Clément O, Luciani A (2004) Imaging the lymphatic system: possibilities and clinical applications. Eur Radiol 14:1498–1507

    PubMed  Google Scholar 

  46. Misselwitz B (2006) MR contrast agents in lymph node imaging. Eur J Radiol 58:375–382

    PubMed  Google Scholar 

  47. Song I, Hyeon T (2009) Inorganic nanoparticles for MRI contrast agents. Adv Mater 21:2133–2148

    Google Scholar 

  48. Hasebroock KM, Serkova NJ (2009) Toxicity of MRI and CT contrast agents. Expert Opin Drug Metab Toxicol 5:403–416

    PubMed  CAS  Google Scholar 

  49. Waters EA, Wickline SA (2008) Contrast agents for MRI. Basic Res Cardiol 103:114–121

    PubMed  CAS  Google Scholar 

  50. Ruehm SG, Schroeder T, Debatin JF (2001) Interstitial MR lymphography with gadoterate meglumine: initial experience in humans. Radiology 220:816–821

    PubMed  CAS  Google Scholar 

  51. Lohrmann C, Foeldi E, Bartholomae J-P, Langer M (2007) Gadoteridol for MR imaging of lymphatic vessels in lymphoedematous patients: initial experience after intracutaneous injection. Br J Radiol 80:569–573

    PubMed  CAS  Google Scholar 

  52. Lohrmann C, Foeldi E, Speck O, Langer M (2006) High-resolution MR lymphangiography in patients with primary and secondary lymphedema. AJR Am J Roentgenol 187:556–561

    PubMed  Google Scholar 

  53. Lohrmann C, Foeldi E, Langer M (2006) Indirect magnetic resonance lymphangiography in patients with lymphedema preliminary results in humans. Eur J Radiol 59:401–406

    PubMed  Google Scholar 

  54. Liu N-F, Lu Q, Jiang Z-H, Wang C-G, Zhou J-G (2009) Anatomic and functional evaluation of the lymphatics and lymph nodes in diagnosis of lymphatic circulation disorders with contrast magnetic resonance lymphangiography. J Vasc Surg 49:980–987

    PubMed  Google Scholar 

  55. Ruddell A et al (2008) Dynamic contrast-enhanced magnetic resonance imaging of tumor-induced lymph flow. Neoplasia 10:706–713, 1 p following 713

    PubMed  Google Scholar 

  56. Matsushima S, Ichiba N, Hayashi D, Fukuda K (2007) Nonenhanced magnetic resonance lymphoductography: visualization of lymphatic system of the trunk on 3-dimensional heavily T2-weighted image with 2-dimensional prospective acquisition and correction. J Comput Assist Tomogr 31:299–302

    PubMed  Google Scholar 

  57. Lu Q et al (2012) Magnetic resonance lymphography at 3T: a promising noninvasive approach to characterise inguinal lymphatic vessel leakage. Eur J Vasc Endovasc Surg 43:106–111

    PubMed  CAS  Google Scholar 

  58. Lu Q, Xu J, Liu N (2010) Chronic lower extremity lymphedema: a comparative study of high-resolution interstitial MR lymphangiography and heavily T2-weighted MRI. Eur J Radiol 73:365–373

    PubMed  Google Scholar 

  59. Kobayashi H et al (2005) Detection of lymph node involvement in hematologic malignancies using micromagnetic resonance lymphangiography with a gadolinium-labeled dendrimer nanoparticle. Neoplasia 7:984–991

    PubMed  Google Scholar 

  60. Corot C, Robert P, Idée J-M, Port M (2006) Recent advances in iron oxide nanocrystal technology for medical imaging. Adv Drug Deliv Rev 58:1471–1504

    PubMed  CAS  Google Scholar 

  61. Ruehm SG, Corot C, Debatin JF (2001) Interstitial MR lymphography with a conventional extracellular gadolinium-based agent: assessment in rabbits. Radiology 218:664–669

    PubMed  CAS  Google Scholar 

  62. Herborn CU et al (2002) Interstitial MR lymphography with MS-325: characterization of normal and tumor-invaded lymph nodes in a rabbit model. AJR Am J Roentgenol 179:1567–1572

    PubMed  Google Scholar 

  63. Mouli SK, Zhao LC, Omary RA, Thaxton CS (2010) Lymphotropic nanoparticle enhanced MRI for the staging of genitourinary tumors. Nat Rev Urol 7:84–93

    PubMed  Google Scholar 

  64. Weissleder R et al (1990) Ultrasmall superparamagnetic iron oxide: an intravenous contrast agent for assessing lymph nodes with MR imaging. Radiology 175:494–498

    PubMed  CAS  Google Scholar 

  65. Bellin MF, Beigelman C, Precetti-Morel S (2000) Iron oxide-enhanced MR lymphography: initial experience. Eur J Radiol 34:257–264

    PubMed  CAS  Google Scholar 

  66. Bellin MF et al (1998) Lymph node metastases: safety and effectiveness of MR imaging with ultrasmall superparamagnetic iron oxide particles – initial clinical experience. Radiology 207:799–808

    PubMed  CAS  Google Scholar 

  67. Réty F et al (2000) MR lymphography using iron oxide nanoparticles in rats: pharmacokinetics in the lymphatic system after intravenous injection. J Magn Reson Imaging 12:734–739

    PubMed  Google Scholar 

  68. Harisinghani M, Barentsz J, Hahn P (2003) Noninvasive detection of clinically occult lymph-node metastases in prostate cancer. N Engl J Med 348:2491–2499

    PubMed  Google Scholar 

  69. Ross RW et al (2009) Lymphotropic nanoparticle-enhanced magnetic resonance imaging (LNMRI) identifies occult lymph node metastases in prostate cancer patients prior to salvage radiation therapy. Clin Imaging 33:301–305

    PubMed  Google Scholar 

  70. Kimura K et al (2010) High-resolution MR lymphography using ultrasmall superparamagnetic iron oxide (USPIO) in the evaluation of axillary lymph nodes in patients with early stage breast cancer: preliminary results. Breast Cancer 17:241–246

    PubMed  Google Scholar 

  71. Kaminskas LM, Porter CJH (2011) Targeting the lymphatics using dendritic polymers (dendrimers). Adv Drug Deliv Rev 63:890–900

    PubMed  CAS  Google Scholar 

  72. Yu SB, Watson AD (1999) Metal-based X-ray contrast media. Chem Rev 99:2353–2378

    PubMed  CAS  Google Scholar 

  73. Suga K, Ogasawara N, Okada M, Matsunaga N (2003) Interstitial CT lymphography-guided localization of breast sentinel lymph node: preliminary results. Surgery 133:170–179

    PubMed  Google Scholar 

  74. Suga K et al (2003) Visualization of breast lymphatic pathways with an indirect computed tomography lymphography using a nonionic monometric contrast medium iopamidol: preliminary results. Invest Radiol 38:73–84

    PubMed  Google Scholar 

  75. Suga K et al (2004) Breast sentinel lymph node mapping at CT lymphography with iopamidol: preliminary experience. Radiology 230:543–552

    PubMed  Google Scholar 

  76. Takahashi M et al (2008) Clinical efficacy and problems with CT lymphography in identifying the sentinel node in breast cancer. World J Surg Oncol 6:57

    PubMed  Google Scholar 

  77. Wu H et al (2009) Preliminary study of indirect CT lymphography-guided sentinel lymph node biopsy in a tongue VX2 carcinoma model. Int J Oral Maxillofac Surg 38:1268–1272

    PubMed  CAS  Google Scholar 

  78. Suga K et al (2005) Breast sentinel lymph node navigation with three-dimensional interstitial multidetector-row computed tomographic lymphography. Invest Radiol 40:336–342

    PubMed  Google Scholar 

  79. Rabin O, Perez J, Grimm J, Wojtkiewicz G (2006) An X-ray computed tomography imaging agent based on long-circulating bismuth sulphide nanoparticles. Nat Mater 5:118–122

    PubMed  CAS  Google Scholar 

  80. Kos S, Haueisen H, Lachmund U, Roeren T (2007) Lymphangiography: forgotten tool or rising star in the diagnosis and therapy of postoperative lymphatic vessel leakage. Cardiovasc Intervent Radiol 30:968–973

    PubMed  Google Scholar 

  81. Silvestri RC, Huseby JS, Rughani I, Thorning D, Culver BH (1980) Respiratory distress syndrome from lymphangiography contrast medium. Am Rev Respir Dis 122:543–549

    PubMed  CAS  Google Scholar 

  82. Tiwari A, Cheng K, Button M, Myint F (2003) Differential diagnosis, investigation, and current treatment of lower limb lymphedema. Arch Surg 138:152–161

    PubMed  Google Scholar 

  83. Vogl TJ, Bartjes M, Marzec K (1997) Contrast-enhanced lymphography. CT or MR imaging? Acta Radiol Suppl 412:47–50

    PubMed  CAS  Google Scholar 

  84. Noroes J, Addiss D, Santos A, Mereidos Z (1996) Ultrasonigraphic evidence of abnormal lymphatic vessels in young men with adult Wuchereria bancrofti infection in the scrotal area. J Urol 156:409–412

    PubMed  CAS  Google Scholar 

  85. Dreyer G, Addiss D, Roberts J, Norões J (2002) Progression of lymphatic vessel dilatation in the presence of living adult Wuchereria bancrofti. Trans R Soc Trop Med Hyg 96:157–161

    PubMed  Google Scholar 

  86. Suresh S et al (1997) Ultrasonographic diagnosis of subclinical filariasis. J Ultrasound Med 16:45–49

    PubMed  CAS  Google Scholar 

  87. Taylor MJ et al (2005) Macrofilaricidal activity after doxycycline treatment of Wuchereria bancrofti: a double-blind, randomised placebo-controlled trial. Lancet 365:2116–2121

    PubMed  CAS  Google Scholar 

  88. Dreyer G et al (1996) Ultrasonographic assessment of the adulticidal efficacy of repeat high-dose ivermectin in bancroftian filariasis. Trop Med Int Health 1:427–432

    PubMed  CAS  Google Scholar 

  89. Noroes J et al (1997) Assessment of the efficacy of diethylcarbamazine on adult Wuchereria bancrofti in vivo. Trans R Soc Trop Med Hyg 91:78–81

    PubMed  CAS  Google Scholar 

  90. Gramiak R, Shah PM, Kramer DH (1969) Ultrasound cardiography: contrast studies in anatomy and function. Radiology 92:939–948

    PubMed  CAS  Google Scholar 

  91. Voigt J-U (2009) Ultrasound molecular imaging. Methods 48:92–97

    PubMed  CAS  Google Scholar 

  92. Dayton PA, Rychak JJ (2007) Molecular ultrasound imaging using microbubble contrast agents. Front Biosci 12:5124–5142

    PubMed  CAS  Google Scholar 

  93. Nielsen KR et al (2009) Sentinel node detection in melanomas using contrast-enhanced ultrasound. Acta Radiol 50:412–417

    Google Scholar 

  94. Wisner ER et al (2003) Sentinel node detection using contrast-enhanced power Doppler ultrasound lymphography. Invest Radiol 38:358–365

    PubMed  Google Scholar 

  95. Goldberg BB et al (2004) Sentinel lymph nodes in a swine model with melanoma: contrast-enhanced lymphatic US. Radiology 230:727–734

    PubMed  Google Scholar 

  96. Sever AR et al (2012) Percutaneous removal of sentinel lymph nodes in a swine model using a breast lesion excision system and contrast-enhanced ultrasound. Eur Radiol 22:545–550

    PubMed  Google Scholar 

  97. Sever A et al (2009) Preoperative localization of sentinel lymph nodes using intradermal microbubbles and contrast-enhanced ultrasonography in patients with breast cancer. Br J Surg 96:1295–1299

    PubMed  CAS  Google Scholar 

  98. Hauff P, Reinhardt M, Briel A, Debus N, Schirner M (2004) Molecular targeting of lymph nodes with L-selectin ligand-specific US contrast agent: a feasibility study in mice and dogs. Radiology 231:667–673

    PubMed  Google Scholar 

  99. Weiler M, Kassis T, Dixon JB (2012) Sensitivity analysis of near-infrared functional lymphatic imaging. J Biomed Opt 17:066019

    PubMed  Google Scholar 

  100. Dixon JB, Zawieja DC, Gashev AA, Cote G (2005) Measuring microlymphatic flow using fast video microscopy. J Biomed Opt 10:064016

    PubMed  Google Scholar 

  101. Dixon JB, Gashev AA, Zawieja DC, Moore JE Jr, Cote G (2007) Image correlation algorithm for measuring lymphocyte velocity and diameter changes in contracting microlymphatics. Ann Biomed Eng 35:387–396

    PubMed  Google Scholar 

  102. Fischer M, Costanzo U, Hoffmann U (1997) Flow velocity of cutaneous lymphatic capillaries in patients with primary lymphedema. J Vasc 17:143–149

    CAS  Google Scholar 

  103. Mellor R et al (2000) Enhanced cutaneous lymphatic network in the forearms of women with postmastectomy oedema. J Vasc Res 37:501–512

    PubMed  CAS  Google Scholar 

  104. McGreevy JM, Cannon MJ, Grissom CB (2003) Minimally invasive lymphatic mapping using fluorescently labeled vitamin B12. J Surg Res 111:38–44

    PubMed  CAS  Google Scholar 

  105. Soltesz EG et al (2005) Intraoperative sentinel lymph node mapping of the lung using near-infrared fluorescent quantum dots. Ann Thorac Surg 79:269–277; discussion 269–277

    PubMed  Google Scholar 

  106. Rao J, Dragulescu-Andrasi A, Yao H (2007) Fluorescence imaging in vivo: recent advances. Curr Opin Biotechnol 18:17–25

    PubMed  CAS  Google Scholar 

  107. CHERRICK GR, STEIN SW, LEEVY CM, DAVIDSON CS (1960) Indocyanine green: observations on its physical properties, plasma decay, and hepatic extraction. J Clin Invest 39:592–600

    PubMed  CAS  Google Scholar 

  108. Philip R, Penzkofer A, Baumler W, Szeimies RM, Abels C (1996) Absorption and fluorescence spectroscopic investigation of indocyanine green. J Photochem Photobiol A 96:137–148

    CAS  Google Scholar 

  109. Saxena V, Sadoqi M, Shao J (2003) Degradation kinetics of indocyanine green in aqueous solution. J Pharm Sci 92:2090–2097

    PubMed  CAS  Google Scholar 

  110. Ohnishi S, Lomnes S, Laurence R (2005) Organic alternatives to quantum dots for intraoperative near-infrared fluorescent sentinel lymph node mapping. Mol Imaging 4:172–181

    PubMed  Google Scholar 

  111. Sevick-Muraca E, Rasmussen J (2008) Molecular imaging with optics: primer and case for near-infrared fluorescence techniques in personalized medicine. J Biomed Opt 13:041303

    PubMed  Google Scholar 

  112. Hutteman M et al (2010) Clinical translation of ex vivo sentinel lymph node mapping for colorectal cancer using invisible near-infrared fluorescence light. Ann Surg Oncol 18:1006–1014

    PubMed  Google Scholar 

  113. Sampath L, Wang W, Sevick-Muraca E (2008) Near infrared fluorescent optical imaging for nodal staging. J Biomed Opt 13:041312

    PubMed  Google Scholar 

  114. Unno N et al (2007) Preliminary experience with a novel fluorescence lymphography using indocyanine green in patients with secondary lymphedema. J Vasc Surg 45:1016

    PubMed  Google Scholar 

  115. Swartz M, Berk D (1996) Transport in lymphatic capillaries. I. Macroscopic measurements using residence time distribution theory. Am J Physiol 270:H324–H329

    PubMed  CAS  Google Scholar 

  116. Berk D, Swartz MA, Leu A, Jain R (1996) Transport in lymphatic capillaries 2. Microscopic velocity measurement with fluorescence photobleaching. Am J Physiol 39:H330–H337

    Google Scholar 

  117. Swartz MA (2001) The physiology of the lymphatic system. Adv Drug Deliv Rev 50:3–20

    PubMed  CAS  Google Scholar 

  118. Sevick-Muraca E et al (2008) Imaging of lymph flow in breast cancer patients after microdose administration of a near-infrared fluorophore: feasibility study1. Radiology 246:734

    PubMed  Google Scholar 

  119. Rasmussen JC et al (2010) Human lymphatic architecture and dynamic transport imaged using near-infrared fluorescence. Transl Oncol 3:362–372

    PubMed  Google Scholar 

  120. Rasmussen J, Tan I (2009) Lymphatic imaging in humans with near-infrared fluorescence. Curr Opin Biotechnol 20:74–82

    PubMed  CAS  Google Scholar 

  121. Rasmussen JC, Kwon S, Sevick-Muraca EM, Cormier JN (2011) The role of lymphatics in cancer as assessed by near-infrared fluorescence imaging. Ann Biomed Eng. doi:10.1007/s10439-011-0476-1

    PubMed  Google Scholar 

  122. Unno N et al (2010) A novel method of measuring human lymphatic pumping using indocyanine green fluorescence lymphography. YMVA 52:946–952

    Google Scholar 

  123. Unno N et al (2011) Influence of age and gender on human lymphatic pumping pressure in the leg. Lymphology 44:113–120

    PubMed  CAS  Google Scholar 

  124. Gashev AA, Nagai T, Bridenbaugh EA (2010) Indocyanine green and lymphatic imaging: current problems. Lymphat Res Biol 8:127–130

    PubMed  CAS  Google Scholar 

  125. Weiler M, Dixon JB (2013) Differential transport function of lymphatic vessels in the rat tail model and the long term effects of Indocyanine Green as assessed with near-infrared imaging. Frontiers in Physiology 4:1–10

    Google Scholar 

  126. Aldrich MB et al (2012) Concentration of indocyanine green does not significantly influence lymphatic function as assessed by near-infrared imaging. Lymphat Res Biol 10:20–24

    PubMed  CAS  Google Scholar 

  127. Davies-Venn CA et al (2011) Albumin-binding domain conjugate for near-infrared fluorescence lymphatic imaging. Mol Imaging Biol. doi:10.1007/s11307-011-0499-x

    Google Scholar 

  128. Proulx ST et al (2010) Quantitative imaging of lymphatic function with liposomal indocyanine green. Cancer Res 70:7053–7062

    PubMed  CAS  Google Scholar 

  129. Luo S, Zhang E, Su Y, Cheng T, Shi C (2011) A review of NIR dyes in cancer targeting and imaging. Biomaterials 32:7127–7138

    PubMed  CAS  Google Scholar 

  130. Karlsen TV, McCormack E, Mujic M, Tenstad O, Wiig H (2012) Minimally invasive quantification of lymph flow in mice and rats by imaging depot clearance of near-infrared albumin. Am J Physiol Heart Circ Physiol 302:H391–H401

    PubMed  CAS  Google Scholar 

  131. Huang D et al (1991) Optical coherence tomography. Science 254:1178–1181

    PubMed  CAS  Google Scholar 

  132. Jung Y, Zhi Z, Wang RK (2010) Three-dimensional optical imaging of microvascular networks within intact lymph node in vivo. J Biomed Opt 15:050501

    PubMed  Google Scholar 

  133. Vakoc BJ et al (2009) Three-dimensional microscopy of the tumor microenvironment in vivo using optical frequency domain imaging. Nat Med 15:1219–1223

    PubMed  CAS  Google Scholar 

  134. Jung Y, Reif R, Zeng Y, Wang RK (2011) Three-dimensional high-resolution imaging of gold nanorods uptake in sentinel lymph nodes. Nano Lett 11:2938–2943

    PubMed  CAS  Google Scholar 

  135. Wang LV, Hu S (2012) Photoacoustic tomography: in vivo imaging from organelles to organs. Science 335:1458–1462

    PubMed  CAS  Google Scholar 

  136. Yao J, Maslov K, Hu S, Wang LV (2009) Evans blue dye-enhanced capillary-resolution photoacoustic microscopy in vivo. J Biomed Opt 14:054049

    PubMed  Google Scholar 

  137. Galanzha EI, Shashkov EV, Tuchin VV, Zharov VP (2008) In vivo multispectral, multiparameter, photoacoustic lymph flow cytometry with natural cell focusing, label-free detection and multicolor nanoparticle probes. Cytometry A 73:884–894

    PubMed  Google Scholar 

  138. Kim C, Song K, Gao F, Wang L (2010) Sentinel lymph nodes and lymphatic vessels: noninvasive dual-modality in vivo mapping by using indocyanine green in rats—volumetric spectroscopic photoacoustic imaging and planar fluorescence imaging. Radiology 255:442–450

    PubMed  Google Scholar 

  139. Song L, Kim C, Maslov K, Shung KK, Wang LV (2009) High-speed dynamic 3D photoacoustic imaging of sentinel lymph node in a murine model using an ultrasound array. Med Phys 36:3724–3729

    PubMed  Google Scholar 

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Weiler, M., Dixon, J.B. (2014). Measurements of Lymph Flow. In: Berardesca, E., Maibach, H., Wilhelm, KP. (eds) Non Invasive Diagnostic Techniques in Clinical Dermatology. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-32109-2_36

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