`
`
`
`US008892190B2
`
`(12) United States Patent
`Docherty et al.
`
`(io) Patent No.:
`(45) Date of Patent:
`
`US 8,892,190 B2
`*Nov. 18, 2014
`
`(54) METHOD AND APPARATUS FOR
`PERFORMING INTRA-OPERATIVE
`ANGIOGRAPHY
`
`(75) Inventors: John C. Docherty, Winnipeg (CA);
`Mark Hcwco, Winnipeg (CA);
`Gurpreet Mangat, Markham (CA);
`Robert W. Flower, Hunt Valley, MD
`(US); Seshadri M. Chari, Toronto (CA)
`
`(73) Assignee: National Research Council of Canada,
`Ontario (CA)
`
`( * ) Notice:
`
`Subject to any disclaimer, the term of this
`patent is extended or adjusted under 35
`U.S.C. 154(b) by 0 days.
`This patent is subject to a terminal dis
`claimer.
`
`(21) Appl.No.: 13/419,368
`
`(22) Filed:
`
`Mar. 13, 2012
`
`(65)
`
`Prior Publication Data
`US 2013/0053690 Al
`Feb. 28, 2013
`
`Related U.S. Application Data
`(63) Continuation of application No. 11/106,154, filed on
`Apr. 14,2005, now abandoned, which is a continuation
`of application No. 09/744,034, filed as application No.
`PCT/US00/22088 on Aug. 11, 2000, now Pat. No.
`6,915,154.
`(60) Provisional application No. 60/155,652, filed on Sep.
`24, 1999.
`
`(51)
`
`Int. Cl.
`A61B 5/05
`A61B 1/04
`A61B 5/00
`A61B 5/02
`A61B 5/026
`A61B 5/0275
`
`(2006.01)
`(2006.01)
`(2006.01)
`(2006.01)
`(2006.01)
`(2006.01)
`
`(52) U.S. Cl.
`CPC ................. A61B1/042 (2013.01); A61B 1/043
`(2013.01); A61B 5/0071 (2013.01); A61B
`5/0084 (2013.01); A61B 5/02007 (2013.01);
`A6IB 5/0261 (2013.01); A61B 5/0275
`(2013.01)
`USPC .............................................. 600/431; 424/9.6
`(58) Field of Classification Search
`USPC ..................................... 424/9.6; 600/431, 476
`See application file for complete search history.
`References Cited
`
`(56)
`
`U.S. PATENT DOCUMENTS
`
`4,619,249 A
`4,995,396 A
`
`10/1986 Landry
`2/1991 Inabaetal.
`(Continued)
`
`FOREIGN PATENT DOCUMENTS
`
`CA
`CA
`
`8/1996
`2212257
`3/2000
`241303 3
`(Continued)
`OTHER PUBLICATIONS
`
`Takayama et al. Intraoperative Coronary Angiography Using Fluo
`rescein. Ann Thorac Surg. 51:140-143. 1991.*
`(Continued)
`Primary Examiner — Parikha Mehta
`(74) Attorney, Agent, or Firm — OliffPLC
`(57)
`ABSTRACT
`Method for assessing the patency of a patient’s blood vessel,
`advantageously during or after treatment of that vessel by an
`invasive procedure, comprising administering a fluorescent
`dye to the patient; obtaining at least one angiographic image
`of the vessel portion; and evaluating the at least one angio
`graphic image to assess the patency of the vessel portion.
`Other related methods are contemplated, including methods
`for assessing perfusion in selected body tissue, methods for
`evaluating the potential of vessels for use in creation of AV
`fistulas, methods for determining the diameter of a vessel, and
`methods for locating a vessel located below the surface of a
`tissue.
`
`3 Claims, 1 Drawing Sheet
`
`
`
`US 8,892,190 B2
`Page 2
`
`(56)
`
`References Cited
`U.S. PATENT DOCUMENTS
`
`2/1991 Turnidge
`4,995,398 A
`5/1992 Andersson-Engels et al.
`5,115,137 A
`5,279,298 A
`1/1994 Flower
`6/1994 Hashimoto et al.
`5,318,869 A
`5,375,603 A
`12/1994 Feiler
`2/1995 Flower
`5,394,199 A
`8/1995 Khoobehi et al.
`5,437,274 A
`9/1995 Narciso, Jr.
`5,453,448 A
`4/1996 Palcic et al.
`5,507,287 A
`7/1998 Pratt et al.
`5,785,965 A
`5,851,181 A
`12/1998 Talmor
`7/1999 Borst et al.
`5,927,284 A
`5,951,980 A
`9/1999 Collen
`2/2000 Flock et al.
`6,032,070 A
`6/2000 Gutkowicz-Krusin et al.
`6,081,612 A
`9/2000 Wunderman et al.
`6,122,042 A
`6/2001 Benaron
`6,246,901 B1
`6,272,374 B1
`8/2001 Flock et al.
`8/2001 Alfano et al.
`6,280,386 B1
`9/2001 Imaizumi et al.
`6,293,911 B1
`2/2002 Flower et al.
`6,351,663 B1
`3/2002 Kimura et al.
`6,353,750 B1
`9/2002 Keogh et al.
`6,447,443 B1
`12/2002 Alfheim et al.
`6,498,945 B1
`10/2003 Pfeiffer et al.
`6,631,286 B2
`1/2005 Pang et al.
`6,840,933 B1
`7/2005 Dochertyetal................ 600/431
`6,915,154 Bl*
`8/2005 Docherty et al................ 606/170
`2005/0182434 Al*
`2006/0239921 Al* 10/2006 Mangat et al................... 424/9.6
`2009/0203993 Al*
`8/2009 Mangatetal.................. 600/431
`
`FOREIGN PATENT DOCUMENTS
`
`CN
`CN
`EP
`EP
`JP
`JP
`JP
`JP
`JP
`JP
`JP
`JP
`JP
`JP
`JP
`JP
`JP
`JP
`JP
`JP
`JP
`JP
`JP
`WO
`WO
`wo
`wo
`wo
`wo
`wo
`wo
`wo
`wo
`wo
`wo
`
`1049781
`1200174
`0091805
`0 826 335 Al
`5969721
`59070903
`02-200237
`04-297236
`06-335451
`07-065154
`07-079955
`07-222712
`08-024227
`09308609
`09120033
`10085222
`09309845
`10201707
`10506550
`11137517
`11509748
`3115958
`05264232
`9412092
`9609792
`9669792
`9618415
`9623524
`9639925
`9708538
`9830144
`9900053
`WO 99/47940
`0117561
`0122870
`
`3/1991
`11/1998
`10/1983
`3/1998
`4/1984
`4/1984
`8/1990
`10/1992
`12/1994
`3/1995
`3/1995
`8/1995
`1/1996
`2/1997
`6/1997
`8/1997
`12/1997
`4/1998
`6/1998
`5/1999
`8/1999
`11/2005
`8/2013
`6/1994
`4/1996
`4/1996
`6/19 96
`8/1996
`12/1996
`3/1997
`7/1998
`1/1999
`9/1999
`3/2001
`4/2001
`
`OTHER PUBLICATIONS
`
`Torolc, B. et al. “[Simultaneous digital indocyanine green and fluo
`rescein angiography]” Klinische Monatsblatter fur Augenheilkunde,
`May 1996, vol. 208, No. 5, May 1996, pp. 333-336.
`
`Jagoe, J.R. et al. “Quantification of retinal damage during
`cardiopulmonary bypass,” Third International Conference on Image
`Processing audits Applications (Conf. Publ. No. 307), IEE, 1989,pp.
`319-323.
`Murphy, Douglas B. Fundamentals of light microscopy and elec
`tronic imaging. John Wiley and Sons. 2001. pp. i-xi, 259-281.
`Nakamura, T. et al., Use of Novel Dyes, Commassie Blue, and
`Indocyanine Green in Dye Dilution Methods, Internal Medicine vol.
`14, No. 7, Dec. 1964, pp. 1361-1366.
`Ooyama, Masa, “The S.supth Congress of International YAG Laser
`Symposium,” The 15//! Annual Meeting of Japan Society for Laser
`Medicine, Sun Royal Hotel, Oct. 12, 1994.
`Sakatani, Noninvasive Optical Imaging of the Subarchnoid Space
`and Cerebrospinal Fluid Pathways Based on Near Infrared Fluores
`cence, J. Neurosurg. 87:738-745 (1997).
`Talcayama, T., Intraoperative Coronary Angiography Using Fluores
`cein, Arm. Thoracic Surgery, 51:140-3 (1991).
`TakayamaT,, Intraoperative Coronary Angiography Using Fluores
`cein: Basic Studies and Clinical Application, presented at the 37.sup.
`th Annual Meeting, American College of Angiology, Atlanta, Geor
`gia, Oct. 1990.
`Benson et al., Fluorescence Properties of Indocyanine Green as
`Related to Angiography, Phys. Med. Biol., 23(1):159-163, (1978).
`Boer et al., “Effect of ventilation on first-pass pulmonary retention of
`alfentanil and sufentanil in patients undergoing coronary artery sur
`gery,” British Journal of Anaesthesia, 73:458-463, (1994).
`Boldt et al., “Does the technique of cardiopulmonary bypass affect
`lung water content?”, Eur J Cardio-thorac Surg, 5:22-26, (1991).
`Boldt et al., “Lung management during cardiopulmonary bypass:
`influence on extravascular lung water,” J. Cardiothorac Anesth,
`4(l):73-79, (1990).
`DeGrand et al., “An Operational Near-Infrared Fluorescence Imag
`ing System Prototype for Large Animal Surgery,” Technology in
`Cancer Research & Treatment, 2(6): 1-10, (2003).
`Desai et al., Improving the Quality of Coronary Bypass Surgery with
`Intraoperative Angiography, Cardiac Surgery, 46(8): 1521-1525,
`(2005).
`Flower, “Choroidal Angiography Today and Tomorrow,” Retina,
`12(3)189-190, (1992).
`Flower, “Does Preinjection Binding of Indocyanine Green to Serum
`Actually Improve Angiograms,” Arch Ophthalmol, 112:1137-1139,
`(1994).
`Flower, Effects of free and liposome-encapsulated hemoglobin on
`choroidal vascular plexus blood flow, using the rabbit eye as a model
`system, European Journal of Ophthalmology, 9(2): 103-114, (1999).
`Flower, “Quantification of Indicator Dye Concentration in Ocular
`Bloodvessels,” Exp. Eye Res., 25:103-111, (1977).
`Goldstein et al., “Intraoperative Angiography to Assess Graft Patency
`After Minimally Invasive Coronary Bypass,” Ann Thorac Surg,
`66:1978-1982,(1998).
`Green, et al., “Bum Depth Estimation Using Indocyanine Green
`Fluorescence”, Arch Dermatol, 128:43-49, (1992).
`Hayashi, et al., “Transadventitial localisation of atheromatous
`plaques by fluorescence emission spectrum analysis of mono-L-
`aspartyl-chlorin e6,” Cardiovascular Research, 27:1943-1947,
`(1993).
`International Search Report for International Application No. PCT/
`US00/22088, dated Oct. 18, 2000.
`Keon et al., “Coronary endarterectomy: An adjunct to coronary artery
`bypass grafting,” Surgery, 86(6):859-867, (1979).
`Kitai et al., “Fluorescence Navigation with Indocyanine Green for
`Detecting Sentinel Lymph Nodes in Breast Cancer,” Breast Cancer,
`12(3):211-215, (2005).
`Laub et al., “Experimental use of Fluorescein for Visualization of
`Coronary Arteries,” Vascular Surgery, 23(6):454-457, (1989).
`Lee et al., “Anew method for assessment of changes in retinal blood
`flow,” Medical Eng. Physics, 19(2): 125-130, (1997).
`Lund et al., “Video fluorescein imaging of the skin: description of an
`overviewing technique for functional evaluation of regional cutane
`ous blood perfusion in occlusive arterial disease of the limbs,” Clini
`cal Physiology, 17(6):619-633, (1997).
`May, “Photonic Approaches to Burn Diagnostics”, Biophotonics
`International, pp. 44-50, (1995).
`
`
`
`US 8,892,190 B2
`Page 3
`
`(56)
`
`References Cited
`
`OTHER PUBLICATIONS
`
`Nakamura et al., “Use of Novel Dyes, Coomassie Blue and
`Indocyanine Green in Dye Dilution Method,” Tohoka University,
`NaJcamura Internal Department, The Tuberculosis Prevention Soci
`ety, Tuberculosis Research Laboratory, 17(2):1361-1366, (1964).
`Ogata et al., “Novel Lymphography Using Indocyanine Green Dye
`for Near-InfraredFluorescence Labeling,” Annals of Plastic Surgery,
`58(6):652-656, (2007).
`Ooyama, Masa, “The S.sup.th 8 Congress of International YAG Laser
`Symposium,” The 15.sup.th Annual Meeting of Japan Society for
`Laser Medicine, Sun Royal Hotel, Oct. 12, 1994.
`Reuthebuch et al., “Novadaq SPY: Intraoperative Quality Assess
`ment in Off-Pump Coronary Artery Bypass Grafting,” Chest,
`125(2):418-424, (2004).
`Rubben et al., “Infrared Videoangiofluorography of the Skin with
`Indocyanine Green-Rat Random Cutaneous Flap Model and Results
`in Man,” Microvascular Research, 47:240-251, (1994).
`Rubens et al., “Anew and Simplified Method for Coronary and Graft
`Imaging During CABG,” The Heart Surgery Forum, 5(2): 141-144,
`(2002).
`Sakatani et al., “Noninvasive optical imaging of the subarachnoid
`space and cerebrospinal fluid pathways based on near-infrared fluo
`rescence,” J. Neurosurg, 87:738-745, (1997).
`Salmon et al., “High Resolution Multimode Digital Imaging System
`for Mitosis Studies In Vivo and In Vitro,” Biol. Bull, 187:231-232,
`(1994).
`Siemers et al., “The acoustic advantage of hunting at low heights
`above water: behavioural experiments on the European ’trawling’
`bats Myotis capaccinil, M. dasycneme and M. daubentonii,” Journal
`of Experimental Biology, 204:3843-3854, (2001).
`Skalidis et al., “Regional Coronary Flow and Contractile Reserve in
`Patients with Idiopathic Dilated Cardiomyopathy,” Journal of the
`American College of Cardiology, 44(10):2027-2032, (2004).
`Still etal., “Evaluation of the Circulation of the Reconstructive Flaps
`Using Laser-Induced Fluorescence of Indocyanine Green,” Annals of
`Plastic Surgery, 42(3):266-274, (1999).
`Suma et al., “Coronary Artery Bypass Grafting Without
`Cardiopulmonary Bypass,” Cardiol, 36(2):85-90ac, (2000).
`Taichman et al., “The Use of Cardio-Green for Intraoperative Visu
`alization of the Coronary Circulation: Evaluation of Myocardial Tox
`icity,” Tex Heart Inst. J., 14(2): 133-138, (1987).
`Takahashi et al., “SPYTM.: an innovative intra-operative imaging
`system to evaluate graft patency during off-pump coronary artery
`bypass grafting,” Interactive Cardiovascular and Thoracic Surgery,
`3:479-483, (2004).
`Takayama et al., “Intraoperative Coronary Angiography Using Fluo
`rescein,” The Society of Thoracic Surgeons, 51:140-143, (1991).
`Takayama et al., “Intraoperative Coronary Angiography Using Fluo
`rescein: Basic Studies and Clinical Application,” Vascular Surgery,
`26(3):193-199, (1992).
`Taylor Kenneth M. “Brain Damage During Cardiopulmonary
`Bypass,” Annals of Thoracic Surgery, 65:S20-S26, (1998).
`Unno et al., “Indocyanine Green Fluorescence Angiography for
`Intraoperative Assessment of Blood Flow: A Feasibility Study,” Eur
`J Vase Endovasc Slug, 1-3 (2007).
`Wachi et al., "Characteristics of cerebrospinal fluid circulation in
`infants as detected with MR velocity imaging,” Child’s Nerv Syst,
`11:227-230, (1995).
`Woitzilc et al., “Intraoperative control of extracranial-intracranial
`bypass patency by near-infrared indocyanine green
`videoangiography,” J. Neurosurg, 102:692-698, (2005).
`Wollert et al., “Intraoperative Visualization of Coronary Arteiy Fis
`tula using Medical Dye,” The Thoracic and Cardiovascular Surgeon,
`46:382-383, (1998).
`Yada et al., “In vivo Observation of Subendocardial Microvessels of
`the Beating Porcine Heart using a Needle-probe Videomicroscope
`with a CCD camera”, Circulation Research, 72(5):939-946, (1993).
`Yoneya et al., “Binding Properties of Indocyanine Green in Human
`Blood,” IOVS, 39(7): 1286-1290, (1998).
`
`Yoneya et al., “Improved Visualization of the Choroidal Circulation
`with Indocyanine Green Angiography,” Arch Ophthalmol, 111:1165-
`1166, (1993).
`European Patent Office Opposition Division, Application No ./Patent
`No. 00 955 472.6-1269/1143852, Decision revoking the European
`Patent (Art. 101(3)(b) EPC), Jun. 10, 2010.
`Sato, et al., “Development of a Visualization Method for the
`Microcirculation of Deep Viscera using an Infrared Intravital Micro
`scope System”, Suzuken Memorial Foundation, Dec. 20, 1991.
`English Translation of Sato, et al., “Development of a Visualization
`Method for the Microcirculation of Deep Viscera using an Infrared
`Intravital Microscope System”, Suzuken Memorial Foundation, Dec.
`20, 1991.
`Report on Observation by C2400-75i and ARGUS20 Under Low
`illumination conditions, Jan. 17, 2008.
`Supplementary European Search Report (Jun. 22, 2004).
`Emery, et al., “Revascularization Using Angioplasty and Minimally
`Invasive Techniques Documented by Thermal Imaging”, The Society
`of Thoracic Surgeons, No. 62, Elservier Science Inc., 1996, pp.
`591-593.
`Roberts, etal., “Laparoscopic Infrared Imaging”, Technique, No. 11,
`Surgical Endoscopy, 1997, pp. 1221-1223.
`Van Son, et al., “Thermal Coronary Angiography for Intraoperative
`Testing of Coronary Patency in Congenital Heart Defects”, The Soci
`ety of Thoracic Surgeons, No. 64, Elsevier Science Inc., 1997, pp.
`1499-1500.
`Mohr, et al., “Thermal Coronary Angiography: AMethod for Assess
`ing Graft Patency and Coronary Anatomy in Coronary Bypass Sur
`gery”, The Society of Thoracic Surgeons, No. 63, Elsevier Science
`Inc., 1997, pp. 1506-1507.
`International Searching Authority, “International Preliminary
`Examination Report from PCTUSOO/22088 (N0001/7000WO)”,
`Aug. 11, 2000, Patent Cooperation Treaty.
`Phillips R. R, et al., “Quantification of Diabetic Maculopathy of
`Digital Imaging of the Fundus”, Eye, 5(1): 1991, pp. 130-137.
`Partial European Search Report for EP 10 18 6218, mailed Dec. 16,
`2010.
`Barton, J.K. et al. “Simultaneous irradiation and imaging of blood
`vessels duringpulsed laser delivery.” Lasers in Surgery andMedicine
`1999, vol. 24, No. 3, 1999, pp. 236-243.
`Torolc, B. et al. Abstract of “[Simultaneous digital indocyanine green
`and fluorescein angiography]” Klinische Monatsblatter fur
`Augenheillcunde, May 1996, vol. 208, No. 5, May 1996, pp. 333-336.
`Jagoe, J.R. et al. Abstract of “Quantification of retinal damage during
`cardiopulmonary bypass,” Third International Conference on Image
`Processing and its Applications (Conf. Publ.No. 307), IEE, 1989, pp.
`319-323.
`Ott, “Hepatic Elimination of Indocyanine Green with Special Refer
`ence to Distribution Kinetics and the Influence of Plasma Protein
`Binding,” Thesis. 1998.
`Unno et al., “Indocyanine Green Fluorescence Angiography for
`Intraoperative Assessment of Blood Flow: A Feasibility Study,” Eur
`J Vase Endovasc Surg, 1-3 (2007).
`Wachi et al., “Characteristics of cerebrospinal fluid circulation in
`infants as detected with MR velocity imaging,” Child’s Nery Syst,
`11:227-230, (1995).
`Argus-50/CA, Inter-cellular CA2+ (calcium ion) Image Analysis
`System, Observation and 2-dimensional analysis of Ca2+ concentra
`tion distribution. Fura-2 andlndo-l compatible. Ca2+ concentrations
`are calculated from the fluorescence ratio, Feb. 1992, pp. 1-10.
`Balacumaraswami et al. Does off-pump total arterial grafting
`increase the incidence of intraoperative graft failure?
`Cardiopulmonary Support and Physiology, The Journal of Thoracic
`and Cardiovascular Surgery, Aug. 2004, pp. 238-244.
`C2741, Compact High-Performance Video Camera for Industrial
`Applications with Built-in Contrast Enhancement Circuit, Jun. 1998.
`Tsutsumi et al. “Moisture Detection of Road Surface using Infrared
`Camera,” Reports of the Hokkaido Industrial Research Institute (No.
`297), Issued on Nov. 30, 1998.
`Reuthebuch et al. “Graft Occlusion After Deployment of the Sym
`metry Bypass System,” Clinic for Cardiovascular Surgery, University
`Hospital, Zurich, Switzerland, pp. 1626-1629, 2003.
`
`
`
`US 8,892,190 B2
`Page 4
`
`(56)
`
`References Cited
`
`OTHER PUBLICATIONS
`
`Taggart et al. “Preliminary Experience wiili a Novel Intraoperative
`Fluorescence Imaging Technique to Evaluate the Patency of Bypass
`Grafts in Total Arterial Revascularization,” Department of
`Cardiothoracic Surgery, John Radcliffe Hospital, Oxford, United
`Kingdom, pp. 870-875, 2003.
`
`Wise et al. “Simultaneous Measurement of Blood and Myocardial
`Velocity in the Rat Heart by Phase Contrast MRI Using Sparse
`q-Space Sampling” Journal of Magnetic Resonance Imaging, 2005,
`22, pp. 614-627.
`Young et al. “Depth-of-Focus in Microscopy”, SCIA ’93, Proc. Of
`the 8,/' Scandinavian Conference on Image Analysis, Tromso, Nor
`way, 1993, pp. 493-498.
`
`* cited by examiner
`
`
`
`IIS* Patent
`US. Patent
`
`Nov. 18, 2014
`N0v.18,2014
`
`US 8,892,190 B2
`US 8,892,190 B2
`
`1.3
`
` NH000
`
`
`
`
`
`1
`METHOD AND APPARATUS FOR
`PERFORMING INTRA-OPERATIVE
`ANGIOGRAPHY
`
`CROSS-REFERENCE TO RELATED PATENT
`APPLICATIONS
`
`This application is a continuation of U.S. application Ser.
`No. 11/106,154, filed on Apr. 14, 2005, now abandoned,
`which is a continuation of U.S. application Ser. No. 09/744,
`034, filed on Apr. 27, 2001, now U.S. Pat. No. 6,915,154,
`which is the National Stage of International Application No.
`PCT/US00/22088, filed on Aug. 11, 2000, which claims the
`benefit ofU.S. Provisional Application No. 60/155,652, filed
`Sep. 24, 1999, all of which are hereby incorporated by refer
`ence.
`
`TECHNICAL FIELD OF THE INVENTION
`
`This invention generally pertains to procedures for observ
`ing blood flow through the cardiovascular system of an ani
`mal.
`
`BACKGROUND OF THE INVENTION
`
`Disease and injury affecting the cardiovascular system in
`animals, and particularly humans, are commonplace in
`today’s society. One such disease is atherosclerosis. This
`disease is characterized by partial blockage (stenosis) of a
`blood vessel, typically by a narrowing of one or more arteries.
`In its most severe form, the vessel narrows to the point that it
`becomes completely blocked (occluded). In coronary arter
`ies, stenosis and occlusion often manifest themselves in the
`form of severe chest pains and, potentially, myocardial inf
`arction (heart attack). Not limited to coronary arteries, ath
`erosclerosis can also affect the peripheral vasculature, i.e.,
`arteries (and veins) that circulate blood throughout the arms
`and legs, the carotid arteries, i.e., arteries that carry blood to
`the brain, and intracranial arteries, i.e., arteries that distribute
`blood within the brain.
`One therapy commonly employed in an effort to overcome
`the effects of atherosclerosis in coronary and peripheral ves
`sels is bypass graft surgery. During this procedure, a vascular
`graft, e.g,, a vein or artery or, alternatively, a flexible artificial
`tube, is surgically inserted in a manner that permits blood to
`bypass the stenotic or occluded portion of a native vessel.
`Perhaps the best-known example of bypass graft surgery is
`coronary artery bypass graft (CABG) surgery. In CABG, a
`graft, commonly a saphenous vein or internal mammary
`artery, is harvested or dissected from the patient, respectively,
`and then located within the patient to permit blood flow to
`bypass the stenotic or occluded vessel portion. Alternatively,
`or in addition thereto, a graft may he used to permit blood to
`flow directly from the aorta to a location downstream of a
`stenotic or occluded portion of an artery.
`The success of bypass grafts, at least in terms of clinical
`improvement, depends in significant part upon the ability of
`the treated vessel to remain free of occlusions over both the
`short- and long-term. This freedom from occlusions is com
`monly referred to as vessel patency. Poor patency in the first
`few months after surgery is thought to be the result of various
`factors, with the following believed to be the most significant:
`poor blood circulation, poor coronary arterial runoff, injury to
`the graft during preparation or faulty surgical technique.
`While cardiac surgery in recent years has focused on strat
`egies to minimize trauma to the myocardium, these strategies
`may increase the likelihood of problems if used during vessel
`
`5
`
`10
`
`15
`
`20
`
`25
`
`30
`
`35
`
`40
`
`45
`
`50
`
`55
`
`60
`
`65
`
`US 8,892,190 B2
`
`2
`grafting procedures. For example, while surgical techniques
`now permit CABG to be performed on a beating heart to
`minimize trauma, there exists a concern relating to the quality
`of the resulting graft. The use of limited access incisions
`during CABG procedures has been developed for, at least, the
`revascularization of the left anterior descending arteiy using
`a left internal mammary artery, with the hope of faster recov
`ery, a shorter hospital stay and reduction in cost. However,
`this method has also raised concerns relating to graft quality.
`Indeed, there exist reports of early failure in grafts completed
`rising limited access incisions.
`Other issues affecting CABG procedures are diagnostic in
`nature, and include relatively slow and inaccurate identifica
`tion of stenotic and occluded vessels during the initial phase
`of CABG procedures (as some of these vessels lie within the
`heart tissue which inhibits visual identification), and an
`inability to quickly and accurately determine the extent of
`blood flow through tire relatively smaller downstream vessels
`(and, more generally, whether the graft was successful in
`restoring blood flow to affected tissue) after the graft is com
`pleted.
`Arterial patency issues may arise in therapies that do not
`include grafts. Forexample, patency evaluation is desirablein
`carotid arteries during and after an endarterectomy, in cranial
`vessels during and after neurosurgery, and in the context of
`kidney hemodialysis, wherein an assessment of AV fistula
`patency is desirable. While vessel patency information in
`these contexts may be obtained using X-ray technology, the
`disadvantages mentioned previously remain.
`The extent of blood flow within a particular tissue or por
`tion thereof, commonly referred to as perfusion, is important
`in connection with the diagnosis and treatment of a variety of
`ailments. For example, a perfusion analysis would be desir
`able in the context of a treatment designed to reduce undes
`ired blood flow into tissue, e.g., halting blood flow into a
`tumor. At present, MRI may be used to obtain perfusion
`information, but this information is imprecise and only avail
`able after treatment is completed. This lessens the probability
`that a physician will be able to identify and remedy problems
`during that same procedure, thereby precluding the need for a
`subsequent remedial procedure.
`Another affliction that requires treatment of the circulatory
`system is renal failure. In many cases of renal failure, it is
`desirable to create an AV fistula to provide vascular access for
`hemodialysis. The fistula is created by joining an artery and
`vein by a surgical procedure, providing a vessel having a
`relatively high rate of blood flow. While X-ray technology can
`be used to assist the physician in determining whether the
`creation of a properly functioning fistula is possible, and the
`type of fistula that should be created, the technology suffers
`from the previously mentioned limitations.
`In view of the foregoing, a need exists for a diagnostic
`procedure that permits a physician to evaluate the patency of
`a particular vessel, and particularly vessels that have under
`gone an invasive procedure such as a bypass graft procedure.
`A further need exists for a method of quickly and accurately
`locating a particular stenotic or occluded vessel, such as a
`coronary artery during the initial phase of CABG surgery. In
`addition, improved methods for evaluating the extent of blood
`flow downstream of a graft are needed, e.g., in coronary
`arteries and peripheral vasculature, as are more accurate
`methods for determining the extent of blood perfusion in
`selected body tissue. A need also exists for an improved
`means of identifying candidate vessels for AV fistulas, and of
`obtaining information relevant to a determination of the type
`of fistula that should be created in a patient with renal impair
`ment.
`
`
`
`3
`BRIEF SUMMARY OF THE INVENTION
`
`4
`BRIEF DESCRIPTION OF THE DRAWING
`
`US 8,892,190 B2
`
`The present invention meets the forgoing and other needs
`by providing, in one aspect, a method for assessing the
`patency of an animal’s blood vessel, advantageously during
`an invasive procedure in which the vessel is treated. The
`method comprises the steps of administering a fluorescent
`dye to the animal; obtaining at least one angiographic image
`of the vessel portion; and evaluating the at least one angio
`graphic image to assess the patency of the vessel portion.
`A related aspect provides for assessing blood flow in a
`portion of tissue in an animal wherein the tissue is a candidate
`for an invasive procedure, is undergoing an invasive proce
`dure, or has undergone such a procedure, comprising identi
`fying the tissue portion in the animal; administering a fluo
`rescent dye to the animal; obtaining at least one angiographic
`image of blood flowing through the tissue portion; and exam
`ining the at least one angiographic image to assess blood flow
`in the tissue portion.
`A further aspect of the present invention permits a physi
`cian to accurately determine the extent to which a selected
`portion of body tissue, e.g., heart tissue, tumor, is well per
`fused, to assist in the identification and diagnosis of improp
`erly (or properly) perfused tissue. The method comprises the
`steps of selecting a portion of body tissue to be analyzed;
`administering a fluorescent dye to the patient; obtaining at
`least one angiographic image of the selected tissue; and
`examining the at least one angiographic image to assess the
`extent of blood flow within the selected portion of body
`tissue.
`In a related aspect, the present invention provides a method
`for evaluating chemical agents and other proposed therapies
`in terms of their effect on vasculature. The method comprises
`obtaining a first angiographic image of selected vasculature;
`administering a therapeutic agent; obtaining a second angio
`graphic image of the selected vasculature on a subsequent
`day; and comparing the first and second angiographic images
`to determine if there is any change in vascular density over
`that time period.
`hi another aspect of the present invention, a method of
`locating, in an animal, at least one vessel (or portion thereof)
`residing beneath the surface of vascularized tissue is pro
`vided. The method comprises the steps of administering a
`fluorescent dye to the animal; obtaining at least one angio
`graphic image of the vasculature located beneath the surface
`of the tissue; and examining the at least one angiographic
`image to locate the at least one vessel residing beneath the
`surface of the tissue.
`In a further aspect, the present invention provides an appa
`ratus for determining the diameter of a blood vessel. More
`specifically, the apparatus comprises: a device that emits
`radiation capable of causing fluorescent dye to fluoresce; a
`camera capable of capturing the radiation emitted by the
`fluorescing dye within the blood vessel as an angiographic
`image comprised of a plurality of pixels; and a computer
`comprising a software pro gram that calculates the diameter of
`a blood vessel by comparing the number of pixels that corre
`spond to the blood vessel diameter with the number of pixels
`associated with a preselected unit of measurement.
`These and other features and advantages of the present
`invention will become apparent upon review of the following
`figure and detailed description of the preferred embodiments
`of the present invention.
`
`5
`
`10
`
`15
`
`20
`
`25
`
`30
`
`35
`
`40
`
`45
`
`50
`
`55
`
`60
`
`65
`
`FIG. 1 illustrates in schematic form a preferred embodi
`ment of the apparatus of the present invention.
`
`DETAILED DESCRIPTION OF THE INVENTION
`
`The methods of the present invention are claimed and
`described herein as a series of treatment steps. It should be
`understood that these methods and associated steps may be
`performed in any logical order. Moreover, the methods may
`be performed alone, or in conjunction with other diagnostic
`procedures and treatments administered before, during or
`after such methods and steps set forth therein without depart
`ing from the scope and spirit of the present invention. Further,
`it is contemplated that the term animals as used herein
`includes, but is not limited to, humans.
`Turning now to one aspect of the present invention, a
`method is provided for analyzing the patency of a portion of
`an animal’s blood vessel. The method comprises the steps of
`administering a fluorescent dye to the animal; obtaining at
`least one angiographic image of the vessel portion; and evalu
`ating the at least one angiographic image to assess the patency
`of the vessel portion.
`Illustrative of the vessels whose patency may be evaluated
`in accordance with the inventive method include coronary
`arteries, the peripheral vasculature, carotid arteries, intracra
`nial vessels and AV fistulas. An evaluation of vessel patency
`may be conducted qualitatively by a visual inspection of the
`images and, if desired, quantitatively by obtaining a measure
`ment of vessel diameter, wherein a substantially uniform
`diameter of a particular vessel portion’s lumen is desirable.
`Advantageously, vessel patency may be determined during
`an invasive procedure. For purposes of this and other aspects
`ofthe present invention, an invasive procedure is one in which
`one or more incisions are made in the tissue of an animal, or
`entry of an instrument into an orifice of an animal is under
`taken, to diagnose or treat an affliction or condition that
`directly or indirectly affects vasculature or tissue. The inva
`sive procedure should be understood to continue until the
`incisions are sutured, or the instrument is withdrawn from the
`animal, respectively.
`By way of example, this aspect of the invention contem
`plates a physician, during a single invasive procedure, obtain
`ing angiographic images of acoronaiy artery both priorto and
`after treatment (e.g., bypass). In this way, the physician is able
`to quickly evaluate the patency of the treated vessel. This is
`beneficial because it allows a physician, upon noting a prob
`lem in the treated vess el, to take remedial measures during the
`same invasive procedure, sparing the animal from the trauma
`associated with a subsequent remedial invasive procedure.
`Examples of vessel portions that may benefit from use of
`the inventive method include, but are not limited to, vessels
`that have been subjected to: repair (due to injury, aneurysm
`and/or malformation) or bypass (of coronary arteries or
`peripheral vasculature); endarterectomies; intracranial sur
`gery; creation of AV fistulas; and surgical procedures con
`ducted using an endoscope or related devices.
`Illustrative ofthe types of repair include, but are not limited
`to: lacerated vessels closed by suture or adhesive; removal of
`an aneurysm or other vessel malformation by removing the
`undesired portion of a vessel followed by either joining the
`two remaining ends of the vessel to one another, or the inter
`position and subsequent joining of a natural or synthetic
`vessel graft to the remaining vessel ends.
`Bypass is commonly used when a portion of a bloodvessel,
`typically a stenotic or occluded portion, requires circumven
`
`
`
`5
`tion. Bypass includes, but is not limited to, attaching the ends
`of a graft vessel at locations upstream and downstream of die
`stenosis, occlusion or other problem, as well as grafting one
`end of a relatively healthy artery onto the undesired vessel at
`a l