Skip to main content
Review

Microcirculatory assessment of vascular diseases

Published Online:https://doi.org/10.1024/0301-1526/a000851

Summary. The term “microcirculation” refers to the terminal vascular network of the body, which includes arterioles, capillaries, venules as well as initial lymphatic vessels. Additionally, it insinuates to their unique function in thermoregulation, fluid balance, maintenance of cellular exchange, and metabolism. Disturbances of microvascular function were identified to precede macrovascular involvement in the presence of cardiovascular risk factors and is the hallmark of terminal disease stages like critical limb or acral ischemia. Nevertheless, despite its obvious significance in vascular medicine assessment of microvascular function became increasingly neglected in the clinical institutions during the last decades and seems to play a subordinary role in medical education. We therefore provide an overview over relevant and clinically practicable methods to assess microcirculation in vascular medicine with critical estimations of their pros and cons and their perspectives in the future.

References

  • 1 Ma KF, Kleiss SF, Schuurmann RCL, Bokkers RPH, Ünlü Ç, De Vries JPM. A systematic review of diagnostic techniques to determine tissue perfusion in patients with peripheral arterial disease. Expert Rev Med Devices. 2019;16:697–710. First citation in articleCrossref MedlineGoogle Scholar

  • 2 Mayr V, Hirschl M, Klein-Weigel P, Girardi L, Kundi M. A randomized cross-over trial in patients suspected of PAD on diagnostic accuracy of ankle-brachial index by Doppler-based versus four-point oscillometry based measurements. Vasa. 2019;48:516–22. First citation in articleLinkGoogle Scholar

  • 3 Kröger KGröchenig E (Hrsg.). Nicht invasive Diagnostik angiologischer Krankheitsbilder. 3. Auflage. ABW-Verlag, Berlin. 2017. First citation in articleGoogle Scholar

  • 4 Lanzer PRösch J (ed.). Vascular Diagnostics. Springer-Verlag, Berlin Heidelberg. 1994. First citation in articleCrossrefGoogle Scholar

  • 5 Crawford F, Welch K, Andras A, Chappell FM. Ankle brachial index for the diagnosis of lower limb peripheral arterial disease. Cochrane Database Syst Rev. 2016;9:CD010680. First citation in articleMedlineGoogle Scholar

  • 6 Tehan PE, Barwick AL, Sebastian M, Chuter VH. Diagnostic accuracy of resting systolic toe pressure for diagnosis of peripheral arterial disease in people with and without diabetes: a cross-sectional retrospective case-control study. J Foot Ankle Res. 2017;10:58. First citation in articleCrossref MedlineGoogle Scholar

  • 7 Collins R, Cranny G, Burch J, Aguiar-Ibáñez R, Craig D, Wright K, et al. A systematic review of duplex ultrasound, magnetic resonance angiography, and computed tomography angiography for the diagnosis and assessment of symptomatic, lower limb peripheral arterial disease. Health Technol Assess. 2007;11(iii–iv, xi–xiii):1–184. First citation in articleGoogle Scholar

  • 8 Sörensen BM, Houben AJHM, Berendschot TTJM, Schouten JSAG, Kroon AA, van der Kallen CJH, et al. Hyperglycemia is the main mediator of prediabetes- and type 2 diabetes-associated impairment of microvascular function: The Maastricht study. Diabetes Care. 2017;40:e103–e105. First citation in articleCrossref MedlineGoogle Scholar

  • 9 Martens RJH, Houben AJHM, Kooman JP, Berendschot TTJM, Dagnelie PC, van der Kallen CJH, et al. Microvascular endothelial dysfunction is associated with albuminuria: the Maastricht Study. J Hypertens. 2018;36:1178–87. First citation in articleCrossref MedlineGoogle Scholar

  • 10 Rother U, Lang W. Noninvasive measurements of tissue perfusion in critical limb ischemia. Gefasschirurgie. 2018;23(Suppl 1):8–12. First citation in articleCrossref MedlineGoogle Scholar

  • 11 Kluz J, Małecki R, Adamiec R. Practical importance and modern methods of the evaluation of skin microcirculation during chronic lower limb ischemia in patients with peripheral arterial occlusive disease and/or diabetes. Int Angiol. 2013;32:42–51. First citation in articleMedlineGoogle Scholar

  • 12 Klein-Weigel PF, Sunderkötter C, Sander O. Nailfold capillaroscopy microscopy – an interdisciplinary appraisal. Vasa. 2016;45:353–64. First citation in articleLinkGoogle Scholar

  • 13 Bollinger A, Fagrell B. Clinical Capillaroscopy. A guide to its use in clinical research and practice. Hogrefe & Huber Publishers, Lewiston, N.Y. 1990. First citation in articleGoogle Scholar

  • 14 Fagrell B. Capillaroscopy. In VAS European book on angiology/vascular medicine. 1st edition. Aracne editrice: Canterano; 2018. pp. 239–50. First citation in articleGoogle Scholar

  • 15 Cutolo M, Pizzorni C, Sulli A. Capillaroscopy. Best Pract Res Clin Rheumatol. 2005;19:437–52. First citation in articleCrossref MedlineGoogle Scholar

  • 16 Smith V, Pizzorni C. The videocapillaroscopic technique. In Cutolo M (ed.), Atlas of capillaroscopy in rheumatic diseases. Elservier Srl, Milano. 2010. First citation in articleGoogle Scholar

  • 17 Fahrig C, Heidrich H, Voigt B, Wnuk G. Capillary microscopy of the nailfold in healthy subjects. Int J Microcirc Clin Exp. 1995;15:287–92. First citation in articleCrossref MedlineGoogle Scholar

  • 18 Hoerth C, Kundi M, Katzenschlager R, Hirschl M. Qualitative and quantitative assessment of nailfold capillaries by capillaroscopy in healthy volunteers. Vasa. 2012;41:19–26. First citation in articleLinkGoogle Scholar

  • 19 Maricq HR, LeRoy EC. Patterns of finger capillary abnormalities in connective tissue disease by “wide-field” microscopy. Arthritis Rheum. 1973;16:619–28. First citation in articleCrossref MedlineGoogle Scholar

  • 20 Cutolo M, Sulli A, Pizzorni C, Accardo S. Naifold Videocapillaroscopy assessment of microvascular damage in systemic sclerosis. J Rheumatol. 2000;27:155–60. First citation in articleMedlineGoogle Scholar

  • 21 Cortes S, Cutolo M. Capillarosecopic patterns in rheumatic diseases. Acta Reumatol Port. 2007;32:29–36. First citation in articleMedlineGoogle Scholar

  • 22 Cutolo M, Sulli A, Secchi ME, Olivieri M, Pizzorni C. The contribution of capillaroscopy to the differential diagnosis of connective autoimmune diseases. Best Pract Res Clin Rheumatol. 2007;21:1093–108. First citation in articleCrossref MedlineGoogle Scholar

  • 23 Cutolo M, Matucci Cerinic M. Nailfold capillaroscopy and classification criteria for systemic sclerosis. Clin Exp Rheumatol. 2007;25:663–5. First citation in articleMedlineGoogle Scholar

  • 24 Manfredi A, Sebastiani M, Campomori F, Pipitone N, Giuggioli D, Colaci M, et al. Nailfold videocapillaroscopy alterations in dermatomyositis and systemic sclerosis: Toward identification of a specific pattern. J Rheumatol. 2016;43:1575–80. First citation in articleCrossref MedlineGoogle Scholar

  • 25 Lambova SN, Hermann W, Müller-Ladner U. Comparison of qualitative and quantitative analysis of capillaroscopic findings in patients with rheumatic diseases. Rheumatol Int. 2012;32:3729–35. First citation in articleCrossref MedlineGoogle Scholar

  • 26 Smith V, Thevissen K, Trombetta AC, Pizzorni C, Ruaro B, Piette Y, et al. Nailfold capillaroscopy and clinical applications in systemic sclerosis. Microcirculation. 2016;23:364–72. First citation in articleCrossref MedlineGoogle Scholar

  • 27 Pizzorni C, Sulli A, Paolino S, Ruaro B, Smith V, Trombetta AC, et al. Progression of organ involvement in systemic sclerosis patients with persistent “late” nailfold capillaroscopic pattern of microangiopathy: A prospective study. J Rheumatol. 2017;44:1941–2. First citation in articleCrossref MedlineGoogle Scholar

  • 28 Cutolo M, Melsens K, Wijnant S, Ingegnoli F, Thevissen K, De Keyser F, et al. Nailfold capillaroscopy in systemic lupus erythematosus: A systematic review and critical appraisal. Autoimmun Rev. 2018;17:344–52. First citation in articleCrossref MedlineGoogle Scholar

  • 29 Corominas H, Ortiz-Santamaría V, Castellví I, Moreno M, Morlà R, Clavaguera T, et al. Nailfold capillaroscopic findings in primary Sjögren’s syndrome with and without Raynaud’s phenomenon and/or positive anti-SSA/Ro and anti-SSB/La antibodies. Rheumatol Int. 2016;36:365–9. First citation in articleCrossref MedlineGoogle Scholar

  • 30 Maricq HR, Weinberger AB, LeRoy EC. Early detection of scleroderma-spectrum disorders by in vivo capillary microscopy: a prospective study of patients with Raynaud’s phenomenon. J Rheumatol. 1982;9:289–91. First citation in articleMedlineGoogle Scholar

  • 31 Ingegnoli F, Boracchi P, Gualtierotti R, Lubatti C, Meani L, Zahalkova L, et al. Prognostic model based on nailfold capillaroscopy for identifying Raynaud’s phenomenon patients at high risk for the development of a scleroderma spectrum disorder: PRINCE (prognostic index for nailfold capillaroscopic examination). Arthritis Rheum. 2008;58:2174–82. First citation in articleCrossref MedlineGoogle Scholar

  • 32 Pavlov-Dolijanovic S, Damjanov NS, Stojanovic RM, Vujasinovic Stupar NZ, Stanisavljevic DM. Scleroderma pattern of nailfold capillary changes as predictive value for the development of a connective tissue disease: a follow-up study of 3,029 patients with primary Raynaud’s phenomenon. Rheumatol Int. 2012;32:3039–45. First citation in articleCrossref MedlineGoogle Scholar

  • 33 Rodriguez-Reyna TS, Bertolazzi C, Vargas-Guerrero A, Gutiérrez M, Hernández-Molina G, Audisio M, et al. Can nailfold videocapillaroscopy images be interpreted reliably by different observers? Results of an inter-reader and intra-reader exercise among rheumatologists with different experience in this field. Clin Rheumatol. 2019;38:205–10. First citation in articleCrossref MedlineGoogle Scholar

  • 34 Cutolo M, Melsens K, Herrick AL, Foeldvari I, Deschepper E, De Keyser F, et al. Reliability of simple capillaroscopic definitions in describing capillary morphology in rheumatic diseases. Rheumatology (Oxford). 2018;57:757–9. First citation in articleCrossref MedlineGoogle Scholar

  • 35 Maricq HR, LeRoy EC, D’Angelo WA, Medsger TA Jr., Rodnan GP, Sharp GC, et al. Diagnostic potential of in vivo capillary microscopy in scleroderma and related disorders. Arthritis Rheumat. 1980;23:183–9. First citation in articleCrossref MedlineGoogle Scholar

  • 36 Marcoccia A, Rossi M. Raynaud Related Diseases. In VAS European book on angiology/vascular medicine. 1st edition. Aracne editrice, Canterano; 2018. pp. 907–16. First citation in articleGoogle Scholar

  • 37 Cutolo M, Melsens K, Wijnant S, Ingegnoli F, Thevissen K, De Keyser F, et al. Nailfold capillaroscopy in systemic lupus erythematosus: A systematic review and critical appraisal. Autoimmun Rev. 2018;17:344–52. First citation in articleCrossref MedlineGoogle Scholar

  • 38 Candela M, Pansoni A, De Carolis ST, Pomponio G, Corvetta A, Gabrielli A, et al. Nailfold capillary microscopy in patients with antiphospholipid syndrome. Recenti Prog Med. 1998;89:444–9. First citation in articleMedlineGoogle Scholar

  • 39 Sander O, Sunderkötter C, Kötter I, Wagner I, Becker M, Herrgott I, et al. Capillaroscopy. Procedure and nomenclature. Z Rheumatol. 2010;69:253–62. First citation in articleCrossref MedlineGoogle Scholar

  • 40 Aslanidis S, Pyrpasopoulou A, Doumas M, Triantafyllou A, Chatzimichailidou S, Zamboulis C. Association of capillaroscopic microhaemorrhages with clinical and immunological antiphospholipid syndrome. Clin Exp Rheumatol. 2011;29:307–9. First citation in articleMedlineGoogle Scholar

  • 41 Sebastiani M, Manfredi A, Colaci M, D’Àmico R, Malagoli V, Giuggioli D, et al. Capillaroscopic Skin Ulcer Risk Index: A new prognostic tool for digital skin ulcer development in systemic sclerosis patients. Arthritis & Rheumatism (Arthritis Care & Research). 2009;61:688–94. First citation in articleCrossref MedlineGoogle Scholar

  • 42 Sebastiani M, Manfredi A, Vukatana G, Moscatelli S, Riato L, Bocci M, et al. Predictive role of capillaroscopic skin ulcer risk index in systemic sclerosis: a multicentre validation study. Ann Rheum Dis. 2012;71:67–70. First citation in articleCrossref MedlineGoogle Scholar

  • 43 Monticone G, Colonna L, Palermi G, Bono R, Puddu P. Quantitative nailfold capillary microscopy findings in patients with acrocyanosis compared with patients having systemic sclerosis and control subjects. J Am Acad Dermatol. 2000;42:787–90. First citation in articleCrossref MedlineGoogle Scholar

  • 44 Fagrell B, Lundberg G. A simplified evaluation of vital capillary microscopy for predicting skin viability in patients with severe arterial insufficiency. Clin Physiol. 1984;4:403–11. First citation in articleCrossref MedlineGoogle Scholar

  • 45 Steins A, Hahn M, Jünger M. Venous leg ulcers and microcirculation. Clin Hemorheol Microcirc. 2001;24:147–53. First citation in articleMedlineGoogle Scholar

  • 46 Jünger M, Steins A, Hahn M, Häfner HM. Microcirculatory dysfunction in chronic venous insufficiency (CVI). Microcirculation. 2000;7:S3–12. First citation in articleCrossref MedlineGoogle Scholar

  • 47 Jammal M, Kettaneh A, Cabane J, Tiev K, Toledano C. Periungueal capillaroscopy: an easy and reliable method to evaluate all microcirculation diseases. Rev Med Interne. 2015;36:603–12. First citation in articleCrossref MedlineGoogle Scholar

  • 48 do Amaral Tafner PF, et al. Recent advances in bedside microcirculation assessment in critically ill patients. Rev Bras Ter Intensiva. 2017;29:238–247. First citation in articleMedlineGoogle Scholar

  • 49 Scorcella C, Damiani E, Domizi R, Pierantozzi S, Tondi S, Carsetti A, et al. MicroDAIMON study: Microcirculatory DAIly MONitoring in critically ill patients: a prospective observational study. Ann Intens Care. 2018;8:64. First citation in articleCrossref MedlineGoogle Scholar

  • 50 Hilty MP, Guerci P, Ince Y, Toraman F, Ince C. MicroTools enables automated quantification of capillary density and red blood cell velocity in handheld vital microscopy. Commun Biol. 2019;2:217. First citation in articleCrossref MedlineGoogle Scholar

  • 51 Clendenon SG, Fu X, Von Hoene RA, Clendenon JL, Sluka JP, Winfree S, et al. A simple automated method for continuous fieldwise measurement of microvascular hemodynamics. Microvasc Res. 2019;123:7–13. First citation in articleCrossref MedlineGoogle Scholar

  • 52 Cheng C, Lee CW, Daskalakis C. A reproducible computerized method for quantitation of capillary density using nailfold capillaroscopy. J Vis Exp. 2015;e53088. First citation in articleMedlineGoogle Scholar

  • 53 Martini R, Abraham P, Laser Doppler fluxmetry. In VAS European Book on Angiology/Vascular Medicine. 1st edition. Aracne editrice, Canterano, pp. 251–5. First citation in articleGoogle Scholar

  • 54 Wardell K, Jakobsson A, Nilsson GE. Laser Doppler perfusion imaging by dynamic light scattering. IEEE Trans Biomed Eng. 1993;40:309–16. First citation in articleCrossref MedlineGoogle Scholar

  • 55 Fredriksson I, Larsson M. On the equivalence and differences between laser Doppler flowmetry and laser speckle contrast analysis. J Biomed Opt. 2016;21(12):126018. First citation in articleCrossref MedlineGoogle Scholar

  • 56 Briers JD, Webster S, Laser speckle contrast analysis (LASCA): a nonscanning, full-field technique for monitoring capillary blood flow. J Biomed Opt. 1996;1:174–9. First citation in articleCrossref MedlineGoogle Scholar

  • 57 Ruaro B, Sulli A, Alessandri E, Pizzorni C, Ferrari G, Cutolo M. Laser speckle contrast analysis: a new method to evaluate peripheral blood perfusion in systemic sclerosis patients. Ann Rheum Dis. 2014;73:1181–5. First citation in articleCrossref MedlineGoogle Scholar

  • 58 Sulli A, Ruaro B, Cutolo M. Evaluation of blood perfusion by laser speckle contrast analysis in different areas of hands and face in patients with systemic sclerosis. Ann Rheum Dis. 2014;73:2059–61. First citation in articleCrossref MedlineGoogle Scholar

  • 59 Ruaro B, Sulli A, Pizzorni C, Paolino S, Smith V, Cutolo M. Correlations between skin blood perfusion values and nailfold capillaroscopy scores in systemic sclerosis patients. Microvasc Res. 2016;105:119–24. First citation in articleCrossref MedlineGoogle Scholar

  • 60 Ruaro B, Paolino S, Pizzorni C, Cutolo M, Sulli A. Assessment of treatment effects on digital ulcer and blood perfusion by laser speckle contrast analysis in a patient affected by systemic sclerosis. Reumatismo. 2017;69:134–6. First citation in articleCrossref MedlineGoogle Scholar

  • 61 Ruaro B, Sulli A, Smith V, Paolino S, Pizzorni C, Cutolo M. Short-term follow-up of digital ulcers by laser speckle contrast analysis in systemic sclerosis patients. Microvasc Res. 2015;101:82–5. First citation in articleCrossref MedlineGoogle Scholar

  • 62 Cutolo M, Vanhaecke A, Ruaro B, Deschepper E, Ickinger C, Melsens K, et al. Is laser speckle contrast analysis (LASCA) the new kid on the block in systemic sclerosis? A systematic literature review and pilot study to evaluate reliability of LASCA to measure peripheral blood perfusion in scleroderma patients. Autoimmun Rev. 2018;17:775–80. First citation in articleCrossref MedlineGoogle Scholar

  • 63 Lambrecht V, Cutolo M, De Keyser F, Decuman S, Ruaro B, Sulli A, et al. Reliability of the quantitative assessment of peripheral blood perfusion by laser speckle contrast analysis in a systemic sclerosis cohort. Ann Rheum Dis. 2016;75:1263–4. First citation in articleCrossref MedlineGoogle Scholar

  • 64 Gschwandtner ME, Ambrozy E, Fasching S, Willfort A, Schneider B, Bohler K, et al. Microcirculation in venous ulcers and the surrounding skin: findings with capillary microscopy and a laser Doppler imager. Eur J Clin Invest. 1999;29:708–16. First citation in articleCrossref MedlineGoogle Scholar

  • 65 Gschwandtner ME, Ambrozy E, Schneider B, Fasching S, Willfort A, Ehringer H. Laser Doppler imaging and capillary microscopy in ischemic ulcers. Atherosclerosis. 1999;142:225–32. First citation in articleCrossref MedlineGoogle Scholar

  • 66 Gschwandtner ME, Ambrozy E, Maric S, Willfort A, Schneider B, Bohler K, et al. Microcirculation is similar in ischemic and venous ulcers. Microvasc Res. 2001;62:226–35. First citation in articleCrossref MedlineGoogle Scholar

  • 67 Gschwandtner ME, Ehringer H. Microcirculation in chronic venous insufficiency. Vasc Med. 2001;6:169–79. First citation in articleCrossref MedlineGoogle Scholar

  • 68 Gschwandtner ME, Koppensteiner R, Maca T, Minar E, Schneider B, Schnurer G, et al. Spontaneous laser Doppler flux distribution in ischemic ulcers and the effect of prostanoids: A crossover study comparing the acute action of prostaglandin E(1) and iloprost vs saline. Microvasc Res. 1996;51:29–38. First citation in articleCrossref MedlineGoogle Scholar

  • 69 Hoeksema H, Van de Sijpe K, Tondu T, Hamdi M, Van LK, Blondeel P, et al. Accuracy of early burn depth assessment by laser Doppler imaging on different days post burn. Burns. 2009;35:36–45. First citation in articleCrossref MedlineGoogle Scholar

  • 70 Ragol S, Remer I, Shoham Y, Hazan S, Willenz U, Sinelnikov I, et al. Static laser speckle contrast analysis for noninvasive burn diagnosis using a camera-phone imager. J Biomed Opt. 2015;20(8):86009. First citation in articleCrossref MedlineGoogle Scholar

  • 71 Beckert S, Witte MB, Königsrainer A, Coerper S. The impact of the Micro-Lightguide O2C for the quantification of tissue ischemia in diabetic foot ulcers. Diabetes Care. 2004;27:2863–7. First citation in articleCrossref MedlineGoogle Scholar

  • 72 Jørgensen LP, Schroeder TV. Micro-lightguide spectrophotometry for tissue perfusion in ischemic limbs. J Vasc Surg. 2012;56:746–52. First citation in articleCrossref MedlineGoogle Scholar

  • 73 Weber K, Gebauer K, Lüders F, Meyborg M, Malyar N, Goerge T, et al. Micro-lightguide spectrophotometry (O2C®) as a predictor of intermediate outcome in patients with critical limb ischemia after percutaneous transluminal angioplasty (PTA). Int Angiol. 2014;33:518–2. First citation in articleMedlineGoogle Scholar

  • 74 Clark LC Jr, Wolf R, Granger D, Taylor Z. Continuous recording of blood oxygen tensions by polarography. J Appl Physiol. 1953;6:189–93. First citation in articleCrossref MedlineGoogle Scholar

  • 75 Whalen WJ, Riley J, Nair P. A microelectrode for measuring intracellular PO2. J Appl Physiol. 1967;23:798–801. First citation in articleCrossref MedlineGoogle Scholar

  • 76 Sheffield PJ. Measuring tissue oxygen tension: a review. Undersea Hyperb Med. 1998;25:179–88. First citation in articleMedlineGoogle Scholar

  • 77 Scheffler A, Rieger H. Clinical information content of transcutaneous oximetry (tcpO2) in peripheral arterial occlusive disease (a review of the methodological and clinical literature with a special reference to critical limb ischaemia). Vasa. 1992;21(2):111–26. First citation in articleMedlineGoogle Scholar

  • 78 Wang Z, Hasan R, Firwana B, Elraiyah T, Tsapas A, Prokop L, et al. A systematic review and meta-analysis of tests to predict wound healing in diabetic foot. J Vasc Surg. 2016;63(2 Suppl):29S–36S.e1–2. First citation in articleCrossref MedlineGoogle Scholar

  • 79 Brownrigg JR, Hinchliffe RJ, Apelqvist J, Boyko EJ, Fitridge R, Mills JL, et al. Performance of prognostic markers in the prediction of wound healing or amputation among patients with foot ulcers in diabetes: a systematic review. Diabetes Metab Res Rev. 2016;32(Suppl 1):128–35. First citation in articleCrossref MedlineGoogle Scholar

  • 80 Scheffler A, Rieger H. A comparative analysis of transcutaneous oximetry (tcPO2) during oxygen inhalation and leg dependency in severe peripheral arterial occlusive disease. J Vasc Surg. 1992;16:218–24. First citation in articleCrossref MedlineGoogle Scholar

  • 81 Urban M, Fouasson-Chailloux A, Signolet I, Colas Ribas C, Feuilloy M, Abraham P. Comparison of two devices for measuring exercise transcutaneous oxygen pressures in patients with claudication. Vasa. 2015;44(5):355–62. First citation in articleLinkGoogle Scholar

  • 82 Hauser CJ. Tissue salvage by mapping of skin surface transcutaneous oxygen tension index. Arch Surg. 1987;122:1128–30. First citation in articleCrossref MedlineGoogle Scholar

  • 83 McDowell JW, Thiede WH. Usefulness of the transcutaneous pO2 monitor during exercise testing in adults. Chest. 1980;78:853–5. First citation in articleCrossref MedlineGoogle Scholar

  • 84 Ubbink DT, Gersbach PA, Berg P, Amann W, Gamain J. The best TcpO(2) parametersto predict the efficacy of spinal cord stimulation to improve limb salvage in patients with inoperable critical leg ischemia. Int Angiol. 2003;22:356–63. First citation in articleMedlineGoogle Scholar

  • 85 Redlich U, Xiong YY, Pech M, Tautenhahn J, Halloul Z, Lobmann R, et al. Superiority of transcutaneous oxygen tension measurements in predicting limb salvage after below-the-knee angioplasty: a prospective trial in diabetic patients with critical limb ischemia. Cardiovasc Intervent Radiol. 2011;34:271–9. First citation in articleCrossref MedlineGoogle Scholar

  • 86 Poredos P, Rakovec S, Guzic-Salobir B. Determination of amputation level in ischaemic limbs using tcPO2 measurement. Vasa. 2005;34:108–12. First citation in articleLinkGoogle Scholar

  • 87 Nguyen QT, Tsien RY. Fluorescence-guided surgery with live molecular navigation – a new cutting edge. Nat Rev Cancer. 2013;13:653–62. First citation in articleCrossref MedlineGoogle Scholar

  • 88 Alander JT, Kaartinen I, Laakso A, Pätilä T, Spillmann T, Tuchin VV, et al. A review of indocyanine green fluorescent imaging in surgery. Int J Biomed Imaging. 2012;2012:940585. First citation in articleCrossref MedlineGoogle Scholar

  • 89 Marshall MV, Rasmussen JC, Tan IC, Aldrich MB, Adams KE, Wang X, et al. Near-infrared fluorescence imaging in humans with indocyanine green: A review and update. Open Surg Oncol J. 2010;2:12–25. First citation in articleCrossref MedlineGoogle Scholar

  • 90 Fox IJ, Brooker LG, Haseltine DW, Essex HE, Wood EH. A tricarbocyanine dye for continuous recording of dilution curves in whole blood independent of variations in blood oxygen saturation. Proc Staff Meet Mayo Clin. 1957;32:478–84. First citation in articleMedlineGoogle Scholar

  • 91 Leevy CM, Mendenhall CL, Lesko W, Howard MM. Estimation of hepatic blood flow with indocyanine green. J Clin Invest. 1962;41:1169–79. First citation in articleCrossref MedlineGoogle Scholar

  • 92 Detter C, Wipper S, Russ D, Iffland A, Burdorf L, Thein E, et al. Fluorescent cardiac imaging: a novel intraoperative method for quantitative assessment of myocardial perfusion during graded coronary artery stenosis. Circulation. 2007;116:1007–14. First citation in articleCrossref MedlineGoogle Scholar

  • 93 Flower RW. Injection technique for indocyanine green and sodium fluorescein dye angiography of the eye. Invest Ophthalmol. 1973;12:881–95. First citation in articleMedlineGoogle Scholar

  • 94 Rother U, Amann K, Adler W, Nawroth N, Karampinis I, Keese M, et al. Quantitative assessment of microperfusion by indocyanine green angiography in kidney transplantation resembles chronic morphological changes in kidney specimens. Microcirculation. 2019;26:e12529. First citation in articleCrossref MedlineGoogle Scholar

  • 95 Rother U, Gerken ALH, Karampinis I, Klumpp M, Regus S, Meyer A, et al. Dosing of indocyanine green for intraoperative laser fluorescence angiography in kidney transplantation. Microcirculation. 2017;24(8). First citation in articleCrossref MedlineGoogle Scholar

  • 96 Rother U, Lang W, Horch RE, Ludolph I, Meyer A, Gefeller O, et al. Pilot assessment of the angiosome concept by intra-operative fluorescence angiography after tibial bypass surgery. Eur J Vasc Endovasc Surg. 2018;55:215–21. First citation in articleCrossref MedlineGoogle Scholar

  • 97 Ludolph I, Arkudas A, Schmitz M, Boos AM, Taeger CD, Rother U, et al. Cracking the perfusion code? Laser-assisted Indocyanine Green angiography and combined laser Doppler spectrophotometry for intraoperative evaluation of tissue perfusion in autologous breast reconstruction with DIEP or ms-TRAM flaps. J Plast Reconstr Aesthet Surg. 2016;69:1382–8. First citation in articleCrossref MedlineGoogle Scholar

  • 98 Settembre N, Kauhanen P, Albäck A, Spillerova K, Venermo M. Quality control of the foot revascularization using indocyanine green fluorescence imaging. World J Surg. 2017;41:1919–26. First citation in articleCrossref MedlineGoogle Scholar

  • 99 Terasaki H, Inoue Y, Sugano N, Jibiki M, Kudo T, Lepäntalo M, et al. A quantitative method for evaluating local perfusion using indocyanine green fluorescence imaging. Ann Vasc Surg. 2013;27:1154–61. First citation in articleCrossref MedlineGoogle Scholar

  • 100 Venermo M, Settembre N, Albäck A, Vikatmaa P, Aho PS, Lepäntalo M, et al. Pilot Assessment of the Repeatability of Indocyanine Green Fluorescence Imaging and Correlation with Traditional Foot Perfusion Assessments. Eur J Vasc Endovasc Surg. 2016;52:527–33. First citation in articleCrossref MedlineGoogle Scholar

  • 101 Rother U, Lang W, Horch RE, Ludolph I, Meyer A, Regus S. Microcirculation evaluated by intraoperative fluorescence angiography after tibial bypass surgery. Ann Vasc Surg. 2017;40:190–7. First citation in articleCrossref MedlineGoogle Scholar

  • 102 Hoffmann C, Compton F, Schäfer JH, Steiner U, Fuller TF, Schostak M, et al. Intraoperative assessment of kidney allograft perfusion by laser-assisted indocyanine green fluorescence videography. Transplant Proc. 2010;42:1526–30. First citation in articleCrossref MedlineGoogle Scholar

  • 103 Sekijima M, Tojimbara T, Sato S, Nakamura M, Kawase T, Kai K, et al. An intraoperative fluorescent imaging system in organ transplantation. Transplant Proc. 2004;36:2188–90. First citation in articleCrossref MedlineGoogle Scholar

  • 104 Ghosh SK, Kumar A. Marcello Malpighi (1628–1694): Pioneer of microscopic anatomy and exponent of the scientific revolution of the 17th century. Eur J Anat. 2018;22:433–9. First citation in articleGoogle Scholar

  • 105 Tshisuaka Barbara I. Leeuwenhoek, Antony van. In WE GerabekBD HaageG KeilW Wegner (Hrsg.). Enzyklopädie Medizingeschichte. De Gruyter, Berlin/New York. 2005. S. 833. First citation in articleGoogle Scholar

  • 106 Martinis MD, Ginaldi L. Capillaroscopy opens a window to look inside. Rheumatology (Sunnyvale). 2014;4:e112. First citation in articleCrossrefGoogle Scholar

  • 107 Schlager O, Willfort-Ehringer A, Hammer A, Steiner S, Fritsch M, Giurgea A, et al. Microvascular function is impaired in children with morbid obesity. Vasc Med. 2011;16:97–102. First citation in articleCrossref MedlineGoogle Scholar

  • 108 Schlager O, Hammer A, Willfort-Ehringer A, Fritsch M, Rami-Merhar B, Schober E, et al. Microvascular autoregulation in children and adolescents with type 1 diabetes mellitus. Diabetologia. 2012;55:1633–40. First citation in articleCrossref MedlineGoogle Scholar

  • 109 Schlager O, Widhalm K, Hammer A, Giurgea A, Margeta C, Fritsch M, et al. Familial hypercholesterolemia affects microvascular autoregulation in children. Metabolism. 2013;62:820–7. First citation in articleCrossref MedlineGoogle Scholar

  • 110 Houben AJHM, Martens RJH, Stehouwer CDA. Assessing Microvascular Function in Humans from a Chronic Disease Perspective. J Am Soc Nephrol. 2017;28:3461–72. First citation in articleCrossref MedlineGoogle Scholar

  • 111 Sörensen BM, Houben AJ, Berendschot TT, Schouten JS, Kroon AA, van der Kallen CJ, et al. Prediabetes and type 2 diabetes are associated with generalized microvascular dysfunction: The Maastricht Study. Circulation. 2016;134:1339–52. First citation in articleCrossref MedlineGoogle Scholar

  • 112 Jonk AM, Houben AJ, Schaper NC, de Leeuw PW, Serné EH, Smulders YM, et al. Obesity is associated with impaired endothelial function in the postprandial state. Microvasc Res. 2011;82:423–9. First citation in articleCrossref MedlineGoogle Scholar

  • 113 Jonk AM, Houben AJ, Schaper NC, de Leeuw PW, Serné EH, Smulders YM, et al. Acute angiotensin II receptor blockade improves insulin-induced microvascular function in hypertensive individuals. Microvasc Res. 2011;82:77–83. First citation in articleCrossref MedlineGoogle Scholar