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
`
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`US 8,892,190 B2
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`IIS* Patent
`
`Nov. 18, 2014
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`US 8,892,190 B2
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`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
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`US 8,892,190 B2
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`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.
`
` VISIONSENSE - 1001
` VISIONSENSE v.
` NOVADAQ TECHNOLOGIES
` Page 6 of 12
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`3
`BRIEF SUMMARY OF THE INVENTION
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`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.
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`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 graf