Abstract

Lymphedema affects up to 50% of all breast cancer survivors. Management with pneumatic compression devices (PCDs) is controversial, owing to the lack of methods to directly assess benefit. This pilot study employed an investigational, near-infrared (NIR) fluorescence imaging technique to evaluate lymphatic response to PCD therapy in normal control and breast cancer-related lymphedema (BCRL) subjects. Lymphatic propulsion rate, apparent lymph velocity, and lymphatic vessel recruitment were measured before, during, and after advanced PCD therapy. Lymphatic function improved in all control subjects and all asymptomatic arms of BCRL subjects. Lymphatic function improved in 4 of 6 BCRL affected arms, improvement defined as proximal movement of dye after therapy. NIR fluorescence lymphatic imaging may be useful to directly evaluate lymphatic response to therapy. These results suggest that PCDs can stimulate lymphatic function and may be an effective method to manage BCRL, warranting future clinical trials.

© 2010 OSA

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2010

E. J. Yang, W. B. Park, K. S. Seo, S. W. Kim, C. Y. Heo, and J. Y. Lim, “Longitudinal change of treatment-related upper limb dysfunction and its impact on late dysfunction in breast cancer survivors: a prospective cohort study,” J. Surg. Oncol. 101(1), 84–91 (2010).
[CrossRef] [PubMed]

M. Torres Lacomba, M. J. Yuste Sánchez, A. Zapico Goñi, D. Prieto Merino, O. Mayoral del Moral, E. Cerezo Téllez, and E. Minayo Mogollón, “Effectiveness of early physiotherapy to prevent lymphoedema after surgery for breast cancer: randomised, single blinded, clinical trial,” BMJ 340(jan12 1), b5396 (2010).
[CrossRef] [PubMed]

M. V. Marshall, J. C. Rasmussen, I. C. Tan, M. B. Aldrich, K. E. Adams, X. Wang, C. E. Fife, E. A. Maus, L. A. Smith, and E. M. Sevick-Muraca, “Near-infrared fluorescence imaging in humans with indocyanine green: a review and update,” The Open Surgical Oncology Journal 2(2), 12–25 (2010).
[CrossRef]

2009

R. J. Damstra, H. G. Voesten, W. D. van Schelven, and B. van der Lei, “Lymphatic venous anastomosis (LVA) for treatment of secondary arm lymphedema. A prospective study of 11 LVA procedures in 10 patients with breast cancer related lymphedema and a critical review of the literature,” Breast Cancer Res. Treat. 113(2), 199–206 (2009).
[CrossRef] [PubMed]

K. H. Schmitz, R. L. Ahmed, A. Troxel, A. Cheville, R. Smith, L. Lewis-Grant, C. J. Bryan, C. T. Williams-Smith, and Q. P. Greene, “Weight lifting in women with breast-cancer-related lymphedema,” N. Engl. J. Med. 361(7), 664–673 (2009).
[CrossRef] [PubMed]

T. M. Bennett Britton and A. D. Purushotham, “Understanding breast cancer-related lymphoedema,” Surgeon 7(2), 120–124 (2009).
[CrossRef] [PubMed]

S. A. Khan, “Axillary reverse mapping to prevent lymphedema after breast cancer surgery: defining the limits of the concept,” J. Clin. Oncol. 27(33), 5494–5496 (2009).
[CrossRef] [PubMed]

International Society of Lymphology, “The diagnosis and treatment of peripheral lymphedema. 2009 Concensus Document of the International Society of Lymphology,” Lymphology 42(2), 51–60 (2009).
[PubMed]

R. Ponzone, N. T. Cont, F. Maggiorotto, E. Cassina, P. Mininanni, N. Biglia, and P. Sismondi, “Extensive nodal disease may impair axillary reverse mapping in patients with breast cancer,” J. Clin. Oncol. 27(33), 5547–5551 (2009).
[CrossRef] [PubMed]

J. C. Rasmussen, I. C. Tan, M. V. Marshall, C. E. Fife, and E. M. Sevick-Muraca, “Lymphatic imaging in humans with near-infrared fluorescence,” Curr. Opin. Biotechnol. 20(1), 74–82 (2009).
[CrossRef] [PubMed]

S. M. Schonholz, “Preoperative assessment enables the early detection and successful treatment of lymphedema,” Cancer 115(4), 909, author reply 909–910 (2009).
[CrossRef] [PubMed]

2008

N. L. Stout Gergich, L. A. Pfalzer, C. McGarvey, B. Springer, L. H. Gerber, and P. Soballe, “Preoperative assessment enables the early diagnosis and successful treatment of lymphedema,” Cancer 112(12), 2809–2819 (2008).
[CrossRef] [PubMed]

E. M. Sevick-Muraca and J. C. Rasmussen, “Molecular imaging with optics: primer and case for near-infrared fluorescence techniques in personalized medicine,” J. Biomed. Opt. 13(4), 041303 (2008).
[CrossRef] [PubMed]

E. M. Sevick-Muraca, R. Sharma, J. C. Rasmussen, M. V. Marshall, J. A. Wendt, H. Q. Pham, E. Bonefas, J. P. Houston, L. Sampath, K. E. Adams, D. K. Blanchard, R. E. Fisher, S. B. Chiang, R. Elledge, and M. E. Mawad, “Imaging of lymph flow in breast cancer patients after microdose administration of a near-infrared fluorophore: feasibility study,” Radiology 246(3), 734–741 (2008).
[CrossRef] [PubMed]

S. A. McLaughlin, M. J. Wright, K. T. Morris, G. L. Giron, M. R. Sampson, J. P. Brockway, K. E. Hurley, E. R. Riedel, and K. J. Van Zee, “Prevalence of lymphedema in women with breast cancer 5 years after sentinel lymph node biopsy or axillary dissection: objective measurements,” J. Clin. Oncol. 26(32), 5213–5219 (2008).
[CrossRef] [PubMed]

S. H. Ridner, E. McMahon, M. S. Dietrich, and S. Hoy, “Home-based lymphedema treatment in patients with cancer-related lymphedema or noncancer-related lymphedema,” Oncol. Nurs. Forum 35(4), 671–680 (2008).
[CrossRef] [PubMed]

2007

H. N. Mayrovitz, “Interface pressures produced by two different types of lymphedema therapy devices,” Phys. Ther. 87(10), 1379–1388 (2007).
[PubMed]

2006

O. Wilburn, P. Wilburn, and S. G. Rockson, “A pilot, prospective evaluation of a novel alternative for maintenance therapy of breast cancer-associated lymphedema [ISRCTN76522412],” BMC Cancer 6(1), 84 (2006).
[CrossRef] [PubMed]

2005

J. M. Armer, “The problem of post-breast cancer lymphedema: impact and measurement issues,” Cancer Invest. 23(1), 76–83 (2005).
[PubMed]

P. A. Morgan, P. J. Franks, and C. J. Moffatt, “Health-related quality of life with lymphoedema: a review of the literature,” Int Wound J 2(1), 47–62 (2005).
[CrossRef] [PubMed]

1998

D. S. Ko, R. Lerner, G. Klose, and A. B. Cosimi, “Effective treatment of lymphedema of the extremities,” Arch. Surg. 133(4), 452–458 (1998).
[CrossRef] [PubMed]

1997

M. Boris, S. Weindorf, and S. Lasinkski, “Persistence of lymphedema reduction after noninvasive complex lymphedema therapy,” Oncology 11, 99–109; discussion 110, 113–104 (1997).

1994

M. Boris, S. Weindorf, B. Lasinski, and G. Boris, “Lymphedema reduction by noninvasive complex lymphedema therapy,” Oncology (Huntingt.) 8(9), 95–106, discussion 109–110 (1994) (Williston Park).
[PubMed]

Adams, K. E.

M. V. Marshall, J. C. Rasmussen, I. C. Tan, M. B. Aldrich, K. E. Adams, X. Wang, C. E. Fife, E. A. Maus, L. A. Smith, and E. M. Sevick-Muraca, “Near-infrared fluorescence imaging in humans with indocyanine green: a review and update,” The Open Surgical Oncology Journal 2(2), 12–25 (2010).
[CrossRef]

E. M. Sevick-Muraca, R. Sharma, J. C. Rasmussen, M. V. Marshall, J. A. Wendt, H. Q. Pham, E. Bonefas, J. P. Houston, L. Sampath, K. E. Adams, D. K. Blanchard, R. E. Fisher, S. B. Chiang, R. Elledge, and M. E. Mawad, “Imaging of lymph flow in breast cancer patients after microdose administration of a near-infrared fluorophore: feasibility study,” Radiology 246(3), 734–741 (2008).
[CrossRef] [PubMed]

Ahmed, R. L.

K. H. Schmitz, R. L. Ahmed, A. Troxel, A. Cheville, R. Smith, L. Lewis-Grant, C. J. Bryan, C. T. Williams-Smith, and Q. P. Greene, “Weight lifting in women with breast-cancer-related lymphedema,” N. Engl. J. Med. 361(7), 664–673 (2009).
[CrossRef] [PubMed]

Aldrich, M. B.

M. V. Marshall, J. C. Rasmussen, I. C. Tan, M. B. Aldrich, K. E. Adams, X. Wang, C. E. Fife, E. A. Maus, L. A. Smith, and E. M. Sevick-Muraca, “Near-infrared fluorescence imaging in humans with indocyanine green: a review and update,” The Open Surgical Oncology Journal 2(2), 12–25 (2010).
[CrossRef]

Armer, J. M.

J. M. Armer, “The problem of post-breast cancer lymphedema: impact and measurement issues,” Cancer Invest. 23(1), 76–83 (2005).
[PubMed]

Bennett Britton, T. M.

T. M. Bennett Britton and A. D. Purushotham, “Understanding breast cancer-related lymphoedema,” Surgeon 7(2), 120–124 (2009).
[CrossRef] [PubMed]

Biglia, N.

R. Ponzone, N. T. Cont, F. Maggiorotto, E. Cassina, P. Mininanni, N. Biglia, and P. Sismondi, “Extensive nodal disease may impair axillary reverse mapping in patients with breast cancer,” J. Clin. Oncol. 27(33), 5547–5551 (2009).
[CrossRef] [PubMed]

Blanchard, D. K.

E. M. Sevick-Muraca, R. Sharma, J. C. Rasmussen, M. V. Marshall, J. A. Wendt, H. Q. Pham, E. Bonefas, J. P. Houston, L. Sampath, K. E. Adams, D. K. Blanchard, R. E. Fisher, S. B. Chiang, R. Elledge, and M. E. Mawad, “Imaging of lymph flow in breast cancer patients after microdose administration of a near-infrared fluorophore: feasibility study,” Radiology 246(3), 734–741 (2008).
[CrossRef] [PubMed]

Bonefas, E.

E. M. Sevick-Muraca, R. Sharma, J. C. Rasmussen, M. V. Marshall, J. A. Wendt, H. Q. Pham, E. Bonefas, J. P. Houston, L. Sampath, K. E. Adams, D. K. Blanchard, R. E. Fisher, S. B. Chiang, R. Elledge, and M. E. Mawad, “Imaging of lymph flow in breast cancer patients after microdose administration of a near-infrared fluorophore: feasibility study,” Radiology 246(3), 734–741 (2008).
[CrossRef] [PubMed]

Boris, G.

M. Boris, S. Weindorf, B. Lasinski, and G. Boris, “Lymphedema reduction by noninvasive complex lymphedema therapy,” Oncology (Huntingt.) 8(9), 95–106, discussion 109–110 (1994) (Williston Park).
[PubMed]

Boris, M.

M. Boris, S. Weindorf, and S. Lasinkski, “Persistence of lymphedema reduction after noninvasive complex lymphedema therapy,” Oncology 11, 99–109; discussion 110, 113–104 (1997).

M. Boris, S. Weindorf, B. Lasinski, and G. Boris, “Lymphedema reduction by noninvasive complex lymphedema therapy,” Oncology (Huntingt.) 8(9), 95–106, discussion 109–110 (1994) (Williston Park).
[PubMed]

Brockway, J. P.

S. A. McLaughlin, M. J. Wright, K. T. Morris, G. L. Giron, M. R. Sampson, J. P. Brockway, K. E. Hurley, E. R. Riedel, and K. J. Van Zee, “Prevalence of lymphedema in women with breast cancer 5 years after sentinel lymph node biopsy or axillary dissection: objective measurements,” J. Clin. Oncol. 26(32), 5213–5219 (2008).
[CrossRef] [PubMed]

Bryan, C. J.

K. H. Schmitz, R. L. Ahmed, A. Troxel, A. Cheville, R. Smith, L. Lewis-Grant, C. J. Bryan, C. T. Williams-Smith, and Q. P. Greene, “Weight lifting in women with breast-cancer-related lymphedema,” N. Engl. J. Med. 361(7), 664–673 (2009).
[CrossRef] [PubMed]

Cassina, E.

R. Ponzone, N. T. Cont, F. Maggiorotto, E. Cassina, P. Mininanni, N. Biglia, and P. Sismondi, “Extensive nodal disease may impair axillary reverse mapping in patients with breast cancer,” J. Clin. Oncol. 27(33), 5547–5551 (2009).
[CrossRef] [PubMed]

Cerezo Téllez, E.

M. Torres Lacomba, M. J. Yuste Sánchez, A. Zapico Goñi, D. Prieto Merino, O. Mayoral del Moral, E. Cerezo Téllez, and E. Minayo Mogollón, “Effectiveness of early physiotherapy to prevent lymphoedema after surgery for breast cancer: randomised, single blinded, clinical trial,” BMJ 340(jan12 1), b5396 (2010).
[CrossRef] [PubMed]

Cheville, A.

K. H. Schmitz, R. L. Ahmed, A. Troxel, A. Cheville, R. Smith, L. Lewis-Grant, C. J. Bryan, C. T. Williams-Smith, and Q. P. Greene, “Weight lifting in women with breast-cancer-related lymphedema,” N. Engl. J. Med. 361(7), 664–673 (2009).
[CrossRef] [PubMed]

Chiang, S. B.

E. M. Sevick-Muraca, R. Sharma, J. C. Rasmussen, M. V. Marshall, J. A. Wendt, H. Q. Pham, E. Bonefas, J. P. Houston, L. Sampath, K. E. Adams, D. K. Blanchard, R. E. Fisher, S. B. Chiang, R. Elledge, and M. E. Mawad, “Imaging of lymph flow in breast cancer patients after microdose administration of a near-infrared fluorophore: feasibility study,” Radiology 246(3), 734–741 (2008).
[CrossRef] [PubMed]

Cont, N. T.

R. Ponzone, N. T. Cont, F. Maggiorotto, E. Cassina, P. Mininanni, N. Biglia, and P. Sismondi, “Extensive nodal disease may impair axillary reverse mapping in patients with breast cancer,” J. Clin. Oncol. 27(33), 5547–5551 (2009).
[CrossRef] [PubMed]

Cosimi, A. B.

D. S. Ko, R. Lerner, G. Klose, and A. B. Cosimi, “Effective treatment of lymphedema of the extremities,” Arch. Surg. 133(4), 452–458 (1998).
[CrossRef] [PubMed]

Damstra, R. J.

R. J. Damstra, H. G. Voesten, W. D. van Schelven, and B. van der Lei, “Lymphatic venous anastomosis (LVA) for treatment of secondary arm lymphedema. A prospective study of 11 LVA procedures in 10 patients with breast cancer related lymphedema and a critical review of the literature,” Breast Cancer Res. Treat. 113(2), 199–206 (2009).
[CrossRef] [PubMed]

Dietrich, M. S.

S. H. Ridner, E. McMahon, M. S. Dietrich, and S. Hoy, “Home-based lymphedema treatment in patients with cancer-related lymphedema or noncancer-related lymphedema,” Oncol. Nurs. Forum 35(4), 671–680 (2008).
[CrossRef] [PubMed]

Elledge, R.

E. M. Sevick-Muraca, R. Sharma, J. C. Rasmussen, M. V. Marshall, J. A. Wendt, H. Q. Pham, E. Bonefas, J. P. Houston, L. Sampath, K. E. Adams, D. K. Blanchard, R. E. Fisher, S. B. Chiang, R. Elledge, and M. E. Mawad, “Imaging of lymph flow in breast cancer patients after microdose administration of a near-infrared fluorophore: feasibility study,” Radiology 246(3), 734–741 (2008).
[CrossRef] [PubMed]

Fife, C. E.

M. V. Marshall, J. C. Rasmussen, I. C. Tan, M. B. Aldrich, K. E. Adams, X. Wang, C. E. Fife, E. A. Maus, L. A. Smith, and E. M. Sevick-Muraca, “Near-infrared fluorescence imaging in humans with indocyanine green: a review and update,” The Open Surgical Oncology Journal 2(2), 12–25 (2010).
[CrossRef]

J. C. Rasmussen, I. C. Tan, M. V. Marshall, C. E. Fife, and E. M. Sevick-Muraca, “Lymphatic imaging in humans with near-infrared fluorescence,” Curr. Opin. Biotechnol. 20(1), 74–82 (2009).
[CrossRef] [PubMed]

Fisher, R. E.

E. M. Sevick-Muraca, R. Sharma, J. C. Rasmussen, M. V. Marshall, J. A. Wendt, H. Q. Pham, E. Bonefas, J. P. Houston, L. Sampath, K. E. Adams, D. K. Blanchard, R. E. Fisher, S. B. Chiang, R. Elledge, and M. E. Mawad, “Imaging of lymph flow in breast cancer patients after microdose administration of a near-infrared fluorophore: feasibility study,” Radiology 246(3), 734–741 (2008).
[CrossRef] [PubMed]

Franks, P. J.

P. A. Morgan, P. J. Franks, and C. J. Moffatt, “Health-related quality of life with lymphoedema: a review of the literature,” Int Wound J 2(1), 47–62 (2005).
[CrossRef] [PubMed]

Gerber, L. H.

N. L. Stout Gergich, L. A. Pfalzer, C. McGarvey, B. Springer, L. H. Gerber, and P. Soballe, “Preoperative assessment enables the early diagnosis and successful treatment of lymphedema,” Cancer 112(12), 2809–2819 (2008).
[CrossRef] [PubMed]

Giron, G. L.

S. A. McLaughlin, M. J. Wright, K. T. Morris, G. L. Giron, M. R. Sampson, J. P. Brockway, K. E. Hurley, E. R. Riedel, and K. J. Van Zee, “Prevalence of lymphedema in women with breast cancer 5 years after sentinel lymph node biopsy or axillary dissection: objective measurements,” J. Clin. Oncol. 26(32), 5213–5219 (2008).
[CrossRef] [PubMed]

Greene, Q. P.

K. H. Schmitz, R. L. Ahmed, A. Troxel, A. Cheville, R. Smith, L. Lewis-Grant, C. J. Bryan, C. T. Williams-Smith, and Q. P. Greene, “Weight lifting in women with breast-cancer-related lymphedema,” N. Engl. J. Med. 361(7), 664–673 (2009).
[CrossRef] [PubMed]

Heo, C. Y.

E. J. Yang, W. B. Park, K. S. Seo, S. W. Kim, C. Y. Heo, and J. Y. Lim, “Longitudinal change of treatment-related upper limb dysfunction and its impact on late dysfunction in breast cancer survivors: a prospective cohort study,” J. Surg. Oncol. 101(1), 84–91 (2010).
[CrossRef] [PubMed]

Houston, J. P.

E. M. Sevick-Muraca, R. Sharma, J. C. Rasmussen, M. V. Marshall, J. A. Wendt, H. Q. Pham, E. Bonefas, J. P. Houston, L. Sampath, K. E. Adams, D. K. Blanchard, R. E. Fisher, S. B. Chiang, R. Elledge, and M. E. Mawad, “Imaging of lymph flow in breast cancer patients after microdose administration of a near-infrared fluorophore: feasibility study,” Radiology 246(3), 734–741 (2008).
[CrossRef] [PubMed]

Hoy, S.

S. H. Ridner, E. McMahon, M. S. Dietrich, and S. Hoy, “Home-based lymphedema treatment in patients with cancer-related lymphedema or noncancer-related lymphedema,” Oncol. Nurs. Forum 35(4), 671–680 (2008).
[CrossRef] [PubMed]

Hurley, K. E.

S. A. McLaughlin, M. J. Wright, K. T. Morris, G. L. Giron, M. R. Sampson, J. P. Brockway, K. E. Hurley, E. R. Riedel, and K. J. Van Zee, “Prevalence of lymphedema in women with breast cancer 5 years after sentinel lymph node biopsy or axillary dissection: objective measurements,” J. Clin. Oncol. 26(32), 5213–5219 (2008).
[CrossRef] [PubMed]

Khan, S. A.

S. A. Khan, “Axillary reverse mapping to prevent lymphedema after breast cancer surgery: defining the limits of the concept,” J. Clin. Oncol. 27(33), 5494–5496 (2009).
[CrossRef] [PubMed]

Kim, S. W.

E. J. Yang, W. B. Park, K. S. Seo, S. W. Kim, C. Y. Heo, and J. Y. Lim, “Longitudinal change of treatment-related upper limb dysfunction and its impact on late dysfunction in breast cancer survivors: a prospective cohort study,” J. Surg. Oncol. 101(1), 84–91 (2010).
[CrossRef] [PubMed]

Klose, G.

D. S. Ko, R. Lerner, G. Klose, and A. B. Cosimi, “Effective treatment of lymphedema of the extremities,” Arch. Surg. 133(4), 452–458 (1998).
[CrossRef] [PubMed]

Ko, D. S.

D. S. Ko, R. Lerner, G. Klose, and A. B. Cosimi, “Effective treatment of lymphedema of the extremities,” Arch. Surg. 133(4), 452–458 (1998).
[CrossRef] [PubMed]

Lasinkski, S.

M. Boris, S. Weindorf, and S. Lasinkski, “Persistence of lymphedema reduction after noninvasive complex lymphedema therapy,” Oncology 11, 99–109; discussion 110, 113–104 (1997).

Lasinski, B.

M. Boris, S. Weindorf, B. Lasinski, and G. Boris, “Lymphedema reduction by noninvasive complex lymphedema therapy,” Oncology (Huntingt.) 8(9), 95–106, discussion 109–110 (1994) (Williston Park).
[PubMed]

Lerner, R.

D. S. Ko, R. Lerner, G. Klose, and A. B. Cosimi, “Effective treatment of lymphedema of the extremities,” Arch. Surg. 133(4), 452–458 (1998).
[CrossRef] [PubMed]

Lewis-Grant, L.

K. H. Schmitz, R. L. Ahmed, A. Troxel, A. Cheville, R. Smith, L. Lewis-Grant, C. J. Bryan, C. T. Williams-Smith, and Q. P. Greene, “Weight lifting in women with breast-cancer-related lymphedema,” N. Engl. J. Med. 361(7), 664–673 (2009).
[CrossRef] [PubMed]

Lim, J. Y.

E. J. Yang, W. B. Park, K. S. Seo, S. W. Kim, C. Y. Heo, and J. Y. Lim, “Longitudinal change of treatment-related upper limb dysfunction and its impact on late dysfunction in breast cancer survivors: a prospective cohort study,” J. Surg. Oncol. 101(1), 84–91 (2010).
[CrossRef] [PubMed]

Maggiorotto, F.

R. Ponzone, N. T. Cont, F. Maggiorotto, E. Cassina, P. Mininanni, N. Biglia, and P. Sismondi, “Extensive nodal disease may impair axillary reverse mapping in patients with breast cancer,” J. Clin. Oncol. 27(33), 5547–5551 (2009).
[CrossRef] [PubMed]

Marshall, M. V.

M. V. Marshall, J. C. Rasmussen, I. C. Tan, M. B. Aldrich, K. E. Adams, X. Wang, C. E. Fife, E. A. Maus, L. A. Smith, and E. M. Sevick-Muraca, “Near-infrared fluorescence imaging in humans with indocyanine green: a review and update,” The Open Surgical Oncology Journal 2(2), 12–25 (2010).
[CrossRef]

J. C. Rasmussen, I. C. Tan, M. V. Marshall, C. E. Fife, and E. M. Sevick-Muraca, “Lymphatic imaging in humans with near-infrared fluorescence,” Curr. Opin. Biotechnol. 20(1), 74–82 (2009).
[CrossRef] [PubMed]

E. M. Sevick-Muraca, R. Sharma, J. C. Rasmussen, M. V. Marshall, J. A. Wendt, H. Q. Pham, E. Bonefas, J. P. Houston, L. Sampath, K. E. Adams, D. K. Blanchard, R. E. Fisher, S. B. Chiang, R. Elledge, and M. E. Mawad, “Imaging of lymph flow in breast cancer patients after microdose administration of a near-infrared fluorophore: feasibility study,” Radiology 246(3), 734–741 (2008).
[CrossRef] [PubMed]

Maus, E. A.

M. V. Marshall, J. C. Rasmussen, I. C. Tan, M. B. Aldrich, K. E. Adams, X. Wang, C. E. Fife, E. A. Maus, L. A. Smith, and E. M. Sevick-Muraca, “Near-infrared fluorescence imaging in humans with indocyanine green: a review and update,” The Open Surgical Oncology Journal 2(2), 12–25 (2010).
[CrossRef]

Mawad, M. E.

E. M. Sevick-Muraca, R. Sharma, J. C. Rasmussen, M. V. Marshall, J. A. Wendt, H. Q. Pham, E. Bonefas, J. P. Houston, L. Sampath, K. E. Adams, D. K. Blanchard, R. E. Fisher, S. B. Chiang, R. Elledge, and M. E. Mawad, “Imaging of lymph flow in breast cancer patients after microdose administration of a near-infrared fluorophore: feasibility study,” Radiology 246(3), 734–741 (2008).
[CrossRef] [PubMed]

Mayoral del Moral, O.

M. Torres Lacomba, M. J. Yuste Sánchez, A. Zapico Goñi, D. Prieto Merino, O. Mayoral del Moral, E. Cerezo Téllez, and E. Minayo Mogollón, “Effectiveness of early physiotherapy to prevent lymphoedema after surgery for breast cancer: randomised, single blinded, clinical trial,” BMJ 340(jan12 1), b5396 (2010).
[CrossRef] [PubMed]

Mayrovitz, H. N.

H. N. Mayrovitz, “Interface pressures produced by two different types of lymphedema therapy devices,” Phys. Ther. 87(10), 1379–1388 (2007).
[PubMed]

McGarvey, C.

N. L. Stout Gergich, L. A. Pfalzer, C. McGarvey, B. Springer, L. H. Gerber, and P. Soballe, “Preoperative assessment enables the early diagnosis and successful treatment of lymphedema,” Cancer 112(12), 2809–2819 (2008).
[CrossRef] [PubMed]

McLaughlin, S. A.

S. A. McLaughlin, M. J. Wright, K. T. Morris, G. L. Giron, M. R. Sampson, J. P. Brockway, K. E. Hurley, E. R. Riedel, and K. J. Van Zee, “Prevalence of lymphedema in women with breast cancer 5 years after sentinel lymph node biopsy or axillary dissection: objective measurements,” J. Clin. Oncol. 26(32), 5213–5219 (2008).
[CrossRef] [PubMed]

McMahon, E.

S. H. Ridner, E. McMahon, M. S. Dietrich, and S. Hoy, “Home-based lymphedema treatment in patients with cancer-related lymphedema or noncancer-related lymphedema,” Oncol. Nurs. Forum 35(4), 671–680 (2008).
[CrossRef] [PubMed]

Minayo Mogollón, E.

M. Torres Lacomba, M. J. Yuste Sánchez, A. Zapico Goñi, D. Prieto Merino, O. Mayoral del Moral, E. Cerezo Téllez, and E. Minayo Mogollón, “Effectiveness of early physiotherapy to prevent lymphoedema after surgery for breast cancer: randomised, single blinded, clinical trial,” BMJ 340(jan12 1), b5396 (2010).
[CrossRef] [PubMed]

Mininanni, P.

R. Ponzone, N. T. Cont, F. Maggiorotto, E. Cassina, P. Mininanni, N. Biglia, and P. Sismondi, “Extensive nodal disease may impair axillary reverse mapping in patients with breast cancer,” J. Clin. Oncol. 27(33), 5547–5551 (2009).
[CrossRef] [PubMed]

Moffatt, C. J.

P. A. Morgan, P. J. Franks, and C. J. Moffatt, “Health-related quality of life with lymphoedema: a review of the literature,” Int Wound J 2(1), 47–62 (2005).
[CrossRef] [PubMed]

Morgan, P. A.

P. A. Morgan, P. J. Franks, and C. J. Moffatt, “Health-related quality of life with lymphoedema: a review of the literature,” Int Wound J 2(1), 47–62 (2005).
[CrossRef] [PubMed]

Morris, K. T.

S. A. McLaughlin, M. J. Wright, K. T. Morris, G. L. Giron, M. R. Sampson, J. P. Brockway, K. E. Hurley, E. R. Riedel, and K. J. Van Zee, “Prevalence of lymphedema in women with breast cancer 5 years after sentinel lymph node biopsy or axillary dissection: objective measurements,” J. Clin. Oncol. 26(32), 5213–5219 (2008).
[CrossRef] [PubMed]

Park, W. B.

E. J. Yang, W. B. Park, K. S. Seo, S. W. Kim, C. Y. Heo, and J. Y. Lim, “Longitudinal change of treatment-related upper limb dysfunction and its impact on late dysfunction in breast cancer survivors: a prospective cohort study,” J. Surg. Oncol. 101(1), 84–91 (2010).
[CrossRef] [PubMed]

Pfalzer, L. A.

N. L. Stout Gergich, L. A. Pfalzer, C. McGarvey, B. Springer, L. H. Gerber, and P. Soballe, “Preoperative assessment enables the early diagnosis and successful treatment of lymphedema,” Cancer 112(12), 2809–2819 (2008).
[CrossRef] [PubMed]

Pham, H. Q.

E. M. Sevick-Muraca, R. Sharma, J. C. Rasmussen, M. V. Marshall, J. A. Wendt, H. Q. Pham, E. Bonefas, J. P. Houston, L. Sampath, K. E. Adams, D. K. Blanchard, R. E. Fisher, S. B. Chiang, R. Elledge, and M. E. Mawad, “Imaging of lymph flow in breast cancer patients after microdose administration of a near-infrared fluorophore: feasibility study,” Radiology 246(3), 734–741 (2008).
[CrossRef] [PubMed]

Ponzone, R.

R. Ponzone, N. T. Cont, F. Maggiorotto, E. Cassina, P. Mininanni, N. Biglia, and P. Sismondi, “Extensive nodal disease may impair axillary reverse mapping in patients with breast cancer,” J. Clin. Oncol. 27(33), 5547–5551 (2009).
[CrossRef] [PubMed]

Prieto Merino, D.

M. Torres Lacomba, M. J. Yuste Sánchez, A. Zapico Goñi, D. Prieto Merino, O. Mayoral del Moral, E. Cerezo Téllez, and E. Minayo Mogollón, “Effectiveness of early physiotherapy to prevent lymphoedema after surgery for breast cancer: randomised, single blinded, clinical trial,” BMJ 340(jan12 1), b5396 (2010).
[CrossRef] [PubMed]

Purushotham, A. D.

T. M. Bennett Britton and A. D. Purushotham, “Understanding breast cancer-related lymphoedema,” Surgeon 7(2), 120–124 (2009).
[CrossRef] [PubMed]

Rasmussen, J. C.

M. V. Marshall, J. C. Rasmussen, I. C. Tan, M. B. Aldrich, K. E. Adams, X. Wang, C. E. Fife, E. A. Maus, L. A. Smith, and E. M. Sevick-Muraca, “Near-infrared fluorescence imaging in humans with indocyanine green: a review and update,” The Open Surgical Oncology Journal 2(2), 12–25 (2010).
[CrossRef]

J. C. Rasmussen, I. C. Tan, M. V. Marshall, C. E. Fife, and E. M. Sevick-Muraca, “Lymphatic imaging in humans with near-infrared fluorescence,” Curr. Opin. Biotechnol. 20(1), 74–82 (2009).
[CrossRef] [PubMed]

E. M. Sevick-Muraca, R. Sharma, J. C. Rasmussen, M. V. Marshall, J. A. Wendt, H. Q. Pham, E. Bonefas, J. P. Houston, L. Sampath, K. E. Adams, D. K. Blanchard, R. E. Fisher, S. B. Chiang, R. Elledge, and M. E. Mawad, “Imaging of lymph flow in breast cancer patients after microdose administration of a near-infrared fluorophore: feasibility study,” Radiology 246(3), 734–741 (2008).
[CrossRef] [PubMed]

E. M. Sevick-Muraca and J. C. Rasmussen, “Molecular imaging with optics: primer and case for near-infrared fluorescence techniques in personalized medicine,” J. Biomed. Opt. 13(4), 041303 (2008).
[CrossRef] [PubMed]

Ridner, S. H.

S. H. Ridner, E. McMahon, M. S. Dietrich, and S. Hoy, “Home-based lymphedema treatment in patients with cancer-related lymphedema or noncancer-related lymphedema,” Oncol. Nurs. Forum 35(4), 671–680 (2008).
[CrossRef] [PubMed]

Riedel, E. R.

S. A. McLaughlin, M. J. Wright, K. T. Morris, G. L. Giron, M. R. Sampson, J. P. Brockway, K. E. Hurley, E. R. Riedel, and K. J. Van Zee, “Prevalence of lymphedema in women with breast cancer 5 years after sentinel lymph node biopsy or axillary dissection: objective measurements,” J. Clin. Oncol. 26(32), 5213–5219 (2008).
[CrossRef] [PubMed]

Rockson, S. G.

O. Wilburn, P. Wilburn, and S. G. Rockson, “A pilot, prospective evaluation of a novel alternative for maintenance therapy of breast cancer-associated lymphedema [ISRCTN76522412],” BMC Cancer 6(1), 84 (2006).
[CrossRef] [PubMed]

Sampath, L.

E. M. Sevick-Muraca, R. Sharma, J. C. Rasmussen, M. V. Marshall, J. A. Wendt, H. Q. Pham, E. Bonefas, J. P. Houston, L. Sampath, K. E. Adams, D. K. Blanchard, R. E. Fisher, S. B. Chiang, R. Elledge, and M. E. Mawad, “Imaging of lymph flow in breast cancer patients after microdose administration of a near-infrared fluorophore: feasibility study,” Radiology 246(3), 734–741 (2008).
[CrossRef] [PubMed]

Sampson, M. R.

S. A. McLaughlin, M. J. Wright, K. T. Morris, G. L. Giron, M. R. Sampson, J. P. Brockway, K. E. Hurley, E. R. Riedel, and K. J. Van Zee, “Prevalence of lymphedema in women with breast cancer 5 years after sentinel lymph node biopsy or axillary dissection: objective measurements,” J. Clin. Oncol. 26(32), 5213–5219 (2008).
[CrossRef] [PubMed]

Schmitz, K. H.

K. H. Schmitz, R. L. Ahmed, A. Troxel, A. Cheville, R. Smith, L. Lewis-Grant, C. J. Bryan, C. T. Williams-Smith, and Q. P. Greene, “Weight lifting in women with breast-cancer-related lymphedema,” N. Engl. J. Med. 361(7), 664–673 (2009).
[CrossRef] [PubMed]

Schonholz, S. M.

S. M. Schonholz, “Preoperative assessment enables the early detection and successful treatment of lymphedema,” Cancer 115(4), 909, author reply 909–910 (2009).
[CrossRef] [PubMed]

Seo, K. S.

E. J. Yang, W. B. Park, K. S. Seo, S. W. Kim, C. Y. Heo, and J. Y. Lim, “Longitudinal change of treatment-related upper limb dysfunction and its impact on late dysfunction in breast cancer survivors: a prospective cohort study,” J. Surg. Oncol. 101(1), 84–91 (2010).
[CrossRef] [PubMed]

Sevick-Muraca, E. M.

M. V. Marshall, J. C. Rasmussen, I. C. Tan, M. B. Aldrich, K. E. Adams, X. Wang, C. E. Fife, E. A. Maus, L. A. Smith, and E. M. Sevick-Muraca, “Near-infrared fluorescence imaging in humans with indocyanine green: a review and update,” The Open Surgical Oncology Journal 2(2), 12–25 (2010).
[CrossRef]

J. C. Rasmussen, I. C. Tan, M. V. Marshall, C. E. Fife, and E. M. Sevick-Muraca, “Lymphatic imaging in humans with near-infrared fluorescence,” Curr. Opin. Biotechnol. 20(1), 74–82 (2009).
[CrossRef] [PubMed]

E. M. Sevick-Muraca, R. Sharma, J. C. Rasmussen, M. V. Marshall, J. A. Wendt, H. Q. Pham, E. Bonefas, J. P. Houston, L. Sampath, K. E. Adams, D. K. Blanchard, R. E. Fisher, S. B. Chiang, R. Elledge, and M. E. Mawad, “Imaging of lymph flow in breast cancer patients after microdose administration of a near-infrared fluorophore: feasibility study,” Radiology 246(3), 734–741 (2008).
[CrossRef] [PubMed]

E. M. Sevick-Muraca and J. C. Rasmussen, “Molecular imaging with optics: primer and case for near-infrared fluorescence techniques in personalized medicine,” J. Biomed. Opt. 13(4), 041303 (2008).
[CrossRef] [PubMed]

Sharma, R.

E. M. Sevick-Muraca, R. Sharma, J. C. Rasmussen, M. V. Marshall, J. A. Wendt, H. Q. Pham, E. Bonefas, J. P. Houston, L. Sampath, K. E. Adams, D. K. Blanchard, R. E. Fisher, S. B. Chiang, R. Elledge, and M. E. Mawad, “Imaging of lymph flow in breast cancer patients after microdose administration of a near-infrared fluorophore: feasibility study,” Radiology 246(3), 734–741 (2008).
[CrossRef] [PubMed]

Sismondi, P.

R. Ponzone, N. T. Cont, F. Maggiorotto, E. Cassina, P. Mininanni, N. Biglia, and P. Sismondi, “Extensive nodal disease may impair axillary reverse mapping in patients with breast cancer,” J. Clin. Oncol. 27(33), 5547–5551 (2009).
[CrossRef] [PubMed]

Smith, L. A.

M. V. Marshall, J. C. Rasmussen, I. C. Tan, M. B. Aldrich, K. E. Adams, X. Wang, C. E. Fife, E. A. Maus, L. A. Smith, and E. M. Sevick-Muraca, “Near-infrared fluorescence imaging in humans with indocyanine green: a review and update,” The Open Surgical Oncology Journal 2(2), 12–25 (2010).
[CrossRef]

Smith, R.

K. H. Schmitz, R. L. Ahmed, A. Troxel, A. Cheville, R. Smith, L. Lewis-Grant, C. J. Bryan, C. T. Williams-Smith, and Q. P. Greene, “Weight lifting in women with breast-cancer-related lymphedema,” N. Engl. J. Med. 361(7), 664–673 (2009).
[CrossRef] [PubMed]

Soballe, P.

N. L. Stout Gergich, L. A. Pfalzer, C. McGarvey, B. Springer, L. H. Gerber, and P. Soballe, “Preoperative assessment enables the early diagnosis and successful treatment of lymphedema,” Cancer 112(12), 2809–2819 (2008).
[CrossRef] [PubMed]

Springer, B.

N. L. Stout Gergich, L. A. Pfalzer, C. McGarvey, B. Springer, L. H. Gerber, and P. Soballe, “Preoperative assessment enables the early diagnosis and successful treatment of lymphedema,” Cancer 112(12), 2809–2819 (2008).
[CrossRef] [PubMed]

Stout Gergich, N. L.

N. L. Stout Gergich, L. A. Pfalzer, C. McGarvey, B. Springer, L. H. Gerber, and P. Soballe, “Preoperative assessment enables the early diagnosis and successful treatment of lymphedema,” Cancer 112(12), 2809–2819 (2008).
[CrossRef] [PubMed]

Tan, I. C.

M. V. Marshall, J. C. Rasmussen, I. C. Tan, M. B. Aldrich, K. E. Adams, X. Wang, C. E. Fife, E. A. Maus, L. A. Smith, and E. M. Sevick-Muraca, “Near-infrared fluorescence imaging in humans with indocyanine green: a review and update,” The Open Surgical Oncology Journal 2(2), 12–25 (2010).
[CrossRef]

J. C. Rasmussen, I. C. Tan, M. V. Marshall, C. E. Fife, and E. M. Sevick-Muraca, “Lymphatic imaging in humans with near-infrared fluorescence,” Curr. Opin. Biotechnol. 20(1), 74–82 (2009).
[CrossRef] [PubMed]

Torres Lacomba, M.

M. Torres Lacomba, M. J. Yuste Sánchez, A. Zapico Goñi, D. Prieto Merino, O. Mayoral del Moral, E. Cerezo Téllez, and E. Minayo Mogollón, “Effectiveness of early physiotherapy to prevent lymphoedema after surgery for breast cancer: randomised, single blinded, clinical trial,” BMJ 340(jan12 1), b5396 (2010).
[CrossRef] [PubMed]

Troxel, A.

K. H. Schmitz, R. L. Ahmed, A. Troxel, A. Cheville, R. Smith, L. Lewis-Grant, C. J. Bryan, C. T. Williams-Smith, and Q. P. Greene, “Weight lifting in women with breast-cancer-related lymphedema,” N. Engl. J. Med. 361(7), 664–673 (2009).
[CrossRef] [PubMed]

van der Lei, B.

R. J. Damstra, H. G. Voesten, W. D. van Schelven, and B. van der Lei, “Lymphatic venous anastomosis (LVA) for treatment of secondary arm lymphedema. A prospective study of 11 LVA procedures in 10 patients with breast cancer related lymphedema and a critical review of the literature,” Breast Cancer Res. Treat. 113(2), 199–206 (2009).
[CrossRef] [PubMed]

van Schelven, W. D.

R. J. Damstra, H. G. Voesten, W. D. van Schelven, and B. van der Lei, “Lymphatic venous anastomosis (LVA) for treatment of secondary arm lymphedema. A prospective study of 11 LVA procedures in 10 patients with breast cancer related lymphedema and a critical review of the literature,” Breast Cancer Res. Treat. 113(2), 199–206 (2009).
[CrossRef] [PubMed]

Van Zee, K. J.

S. A. McLaughlin, M. J. Wright, K. T. Morris, G. L. Giron, M. R. Sampson, J. P. Brockway, K. E. Hurley, E. R. Riedel, and K. J. Van Zee, “Prevalence of lymphedema in women with breast cancer 5 years after sentinel lymph node biopsy or axillary dissection: objective measurements,” J. Clin. Oncol. 26(32), 5213–5219 (2008).
[CrossRef] [PubMed]

Voesten, H. G.

R. J. Damstra, H. G. Voesten, W. D. van Schelven, and B. van der Lei, “Lymphatic venous anastomosis (LVA) for treatment of secondary arm lymphedema. A prospective study of 11 LVA procedures in 10 patients with breast cancer related lymphedema and a critical review of the literature,” Breast Cancer Res. Treat. 113(2), 199–206 (2009).
[CrossRef] [PubMed]

Wang, X.

M. V. Marshall, J. C. Rasmussen, I. C. Tan, M. B. Aldrich, K. E. Adams, X. Wang, C. E. Fife, E. A. Maus, L. A. Smith, and E. M. Sevick-Muraca, “Near-infrared fluorescence imaging in humans with indocyanine green: a review and update,” The Open Surgical Oncology Journal 2(2), 12–25 (2010).
[CrossRef]

Weindorf, S.

M. Boris, S. Weindorf, and S. Lasinkski, “Persistence of lymphedema reduction after noninvasive complex lymphedema therapy,” Oncology 11, 99–109; discussion 110, 113–104 (1997).

M. Boris, S. Weindorf, B. Lasinski, and G. Boris, “Lymphedema reduction by noninvasive complex lymphedema therapy,” Oncology (Huntingt.) 8(9), 95–106, discussion 109–110 (1994) (Williston Park).
[PubMed]

Wendt, J. A.

E. M. Sevick-Muraca, R. Sharma, J. C. Rasmussen, M. V. Marshall, J. A. Wendt, H. Q. Pham, E. Bonefas, J. P. Houston, L. Sampath, K. E. Adams, D. K. Blanchard, R. E. Fisher, S. B. Chiang, R. Elledge, and M. E. Mawad, “Imaging of lymph flow in breast cancer patients after microdose administration of a near-infrared fluorophore: feasibility study,” Radiology 246(3), 734–741 (2008).
[CrossRef] [PubMed]

Wilburn, O.

O. Wilburn, P. Wilburn, and S. G. Rockson, “A pilot, prospective evaluation of a novel alternative for maintenance therapy of breast cancer-associated lymphedema [ISRCTN76522412],” BMC Cancer 6(1), 84 (2006).
[CrossRef] [PubMed]

Wilburn, P.

O. Wilburn, P. Wilburn, and S. G. Rockson, “A pilot, prospective evaluation of a novel alternative for maintenance therapy of breast cancer-associated lymphedema [ISRCTN76522412],” BMC Cancer 6(1), 84 (2006).
[CrossRef] [PubMed]

Williams-Smith, C. T.

K. H. Schmitz, R. L. Ahmed, A. Troxel, A. Cheville, R. Smith, L. Lewis-Grant, C. J. Bryan, C. T. Williams-Smith, and Q. P. Greene, “Weight lifting in women with breast-cancer-related lymphedema,” N. Engl. J. Med. 361(7), 664–673 (2009).
[CrossRef] [PubMed]

Wright, M. J.

S. A. McLaughlin, M. J. Wright, K. T. Morris, G. L. Giron, M. R. Sampson, J. P. Brockway, K. E. Hurley, E. R. Riedel, and K. J. Van Zee, “Prevalence of lymphedema in women with breast cancer 5 years after sentinel lymph node biopsy or axillary dissection: objective measurements,” J. Clin. Oncol. 26(32), 5213–5219 (2008).
[CrossRef] [PubMed]

Yang, E. J.

E. J. Yang, W. B. Park, K. S. Seo, S. W. Kim, C. Y. Heo, and J. Y. Lim, “Longitudinal change of treatment-related upper limb dysfunction and its impact on late dysfunction in breast cancer survivors: a prospective cohort study,” J. Surg. Oncol. 101(1), 84–91 (2010).
[CrossRef] [PubMed]

Yuste Sánchez, M. J.

M. Torres Lacomba, M. J. Yuste Sánchez, A. Zapico Goñi, D. Prieto Merino, O. Mayoral del Moral, E. Cerezo Téllez, and E. Minayo Mogollón, “Effectiveness of early physiotherapy to prevent lymphoedema after surgery for breast cancer: randomised, single blinded, clinical trial,” BMJ 340(jan12 1), b5396 (2010).
[CrossRef] [PubMed]

Zapico Goñi, A.

M. Torres Lacomba, M. J. Yuste Sánchez, A. Zapico Goñi, D. Prieto Merino, O. Mayoral del Moral, E. Cerezo Téllez, and E. Minayo Mogollón, “Effectiveness of early physiotherapy to prevent lymphoedema after surgery for breast cancer: randomised, single blinded, clinical trial,” BMJ 340(jan12 1), b5396 (2010).
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Supplementary Material (5)

» Media 1: MPG (3108 KB)     
» Media 2: MPG (1318 KB)     
» Media 3: MPG (1962 KB)     
» Media 4: MPG (2946 KB)     
» Media 5: MPG (5060 KB)     

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Figures (9)

Fig. 1
Fig. 1

Timeline for subjects participating in study.

Fig. 2
Fig. 2

Schematic of the imaging system, which includes (i) a diffused 785 nm NIR laser with a laser clean up filter, (ii) a NIR-sensitive ICCD camera, (iii) holographic and bandpass filters to efficiently collect fluorescent light at 830 nm, and (iv) a computer to control the system and collect the images.

Fig. 3
Fig. 3

Comparison of rate of lymph propulsion (A) and velocity (B) in untreated and treated arms of normal control subjects.

Fig. 4
Fig. 4

The upper arm and axilla of Control Subject 3 before PCD treatment (A, Media 1) and after PCD treatment (B, Media 2). After treatment, recruitment of vessels and increased rate of propulsion are observed.

Fig. 5
Fig. 5

Advancement of ICG in the affected arms of 3 lymphedema subjects after PCD treatment. In two subjects, BCRL 4 and 5, ICG is not present above the elbow pre-treatment (A and B, respectively), whereas the ICG has advanced past the elbow and into the upper arm post-treatment (D and E). In another subject, BCRL 6, prior to treatment (C), the ICG is present only at the injection site, and after treatment (F), the ICG has spread proximally through the arm.

Fig. 6
Fig. 6

Pre- (A) and post- (B and C) PCD treatment images of affected arm of lymphedema subject, BCRL 4. Lymphatic fluid moved towards the axilla (B) and into the shoulder (C) after PCD treatment, as compared with pre-PCD treatment (A).

Fig. 7
Fig. 7

Comparison of lymph propulsion rate (A) and velocity (B) in asymptomatic arm of BCRL subjects and summary of all rate of propulsion results (C).

Fig. 8
Fig. 8

The top of the hand and wrist of the asymptomatic arm of subject BCRL 1 pre- (A, Media 3), during (B, Media 4), and post- (C, Media 5) PCD treatment. The videos display an increased rate of lymphatic propulsion during (B, Media 4) and after (C, Media 5) PCD treatment when compared with before treatment (A, Media 3).

Fig. 9
Fig. 9

Rate of propulsion of “packets” in contralateral arm (1) pre massage, (2) during the trunk and arm preparation phase, (3) during the arm drainage phase, and (4) after the PCD treatment.

Tables (1)

Tables Icon

Table 1 Study subject demographics

Metrics