WO2012149226A2 - Caractérisation à base d'imagerie par résonance magnétique (irm) d'une obstruction microvasculaire en réponse à une hypothermie thérapeutique après un infarctus aigu du myocarde - Google Patents

Caractérisation à base d'imagerie par résonance magnétique (irm) d'une obstruction microvasculaire en réponse à une hypothermie thérapeutique après un infarctus aigu du myocarde Download PDF

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WO2012149226A2
WO2012149226A2 PCT/US2012/035307 US2012035307W WO2012149226A2 WO 2012149226 A2 WO2012149226 A2 WO 2012149226A2 US 2012035307 W US2012035307 W US 2012035307W WO 2012149226 A2 WO2012149226 A2 WO 2012149226A2
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reperfusion
microvascular
myocardial infarction
blood
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WO2012149226A3 (fr
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Rohan Dharmakumar
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Cedars Sinai Medical Center
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Cedars Sinai Medical Center
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F7/00—Heating or cooling appliances for medical or therapeutic treatment of the human body
    • A61F7/10—Cooling bags, e.g. ice-bags
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/0033—Features or image-related aspects of imaging apparatus, e.g. for MRI, optical tomography or impedance tomography apparatus; Arrangements of imaging apparatus in a room
    • A61B5/004—Features or image-related aspects of imaging apparatus, e.g. for MRI, optical tomography or impedance tomography apparatus; Arrangements of imaging apparatus in a room adapted for image acquisition of a particular organ or body part
    • A61B5/0044—Features or image-related aspects of imaging apparatus, e.g. for MRI, optical tomography or impedance tomography apparatus; Arrangements of imaging apparatus in a room adapted for image acquisition of a particular organ or body part for the heart
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/05—Detecting, measuring or recording for diagnosis by means of electric currents or magnetic fields; Measuring using microwaves or radio waves
    • A61B5/055—Detecting, measuring or recording for diagnosis by means of electric currents or magnetic fields; Measuring using microwaves or radio waves involving electronic [EMR] or nuclear [NMR] magnetic resonance, e.g. magnetic resonance imaging
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F7/00—Heating or cooling appliances for medical or therapeutic treatment of the human body
    • A61F7/12—Devices for heating or cooling internal body cavities
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01R—MEASURING ELECTRIC VARIABLES; MEASURING MAGNETIC VARIABLES
    • G01R33/00—Arrangements or instruments for measuring magnetic variables
    • G01R33/20—Arrangements or instruments for measuring magnetic variables involving magnetic resonance
    • G01R33/44—Arrangements or instruments for measuring magnetic variables involving magnetic resonance using nuclear magnetic resonance [NMR]
    • G01R33/48—NMR imaging systems
    • G01R33/54—Signal processing systems, e.g. using pulse sequences ; Generation or control of pulse sequences; Operator console
    • G01R33/56—Image enhancement or correction, e.g. subtraction or averaging techniques, e.g. improvement of signal-to-noise ratio and resolution
    • G01R33/563—Image enhancement or correction, e.g. subtraction or averaging techniques, e.g. improvement of signal-to-noise ratio and resolution of moving material, e.g. flow contrast angiography
    • G01R33/56366—Perfusion imaging
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B2576/00—Medical imaging apparatus involving image processing or analysis
    • A61B2576/02—Medical imaging apparatus involving image processing or analysis specially adapted for a particular organ or body part
    • A61B2576/023—Medical imaging apparatus involving image processing or analysis specially adapted for a particular organ or body part for the heart
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F7/00—Heating or cooling appliances for medical or therapeutic treatment of the human body
    • A61F7/12—Devices for heating or cooling internal body cavities
    • A61F2007/126—Devices for heating or cooling internal body cavities for invasive application, e.g. for introducing into blood vessels
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01R—MEASURING ELECTRIC VARIABLES; MEASURING MAGNETIC VARIABLES
    • G01R33/00—Arrangements or instruments for measuring magnetic variables
    • G01R33/20—Arrangements or instruments for measuring magnetic variables involving magnetic resonance
    • G01R33/44—Arrangements or instruments for measuring magnetic variables involving magnetic resonance using nuclear magnetic resonance [NMR]
    • G01R33/48—NMR imaging systems
    • G01R33/54—Signal processing systems, e.g. using pulse sequences ; Generation or control of pulse sequences; Operator console
    • G01R33/56—Image enhancement or correction, e.g. subtraction or averaging techniques, e.g. improvement of signal-to-noise ratio and resolution
    • G01R33/5602—Image enhancement or correction, e.g. subtraction or averaging techniques, e.g. improvement of signal-to-noise ratio and resolution by filtering or weighting based on different relaxation times within the sample, e.g. T1 weighting using an inversion pulse
    • G—PHYSICS
    • G16—INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR SPECIFIC APPLICATION FIELDS
    • G16H—HEALTHCARE INFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR THE HANDLING OR PROCESSING OF MEDICAL OR HEALTHCARE DATA
    • G16H30/00—ICT specially adapted for the handling or processing of medical images
    • G16H30/40—ICT specially adapted for the handling or processing of medical images for processing medical images, e.g. editing

Definitions

  • the invention is directed to methods for reducing microvascular obstructions by using therapeutic hypothermia and noninvasively monitoring microvascular obstructions using magnetic resonance imaging during reperfusion and post-reperfusion.
  • Myocardial infarction (MI) or acute myocardial infarction (AMI), commonly known as a heart attack is the interruption of blood supply to a part of the heart, causing heart cells to die.
  • Myocardial infarction is caused by ischaemic or ischemic heart disease (IHD), or myocardial ischaemia, which is characterized by reduced blood supply due to a partial or complete blockage of an artery that carries blood to the heart, usually due to coronary artery disease (atherosclerosis of the coronary arteries). The decrease in blood flow reduces the heart's oxygen supply.
  • Myocardial ischemia is an imbalance between myocardial oxygen supply and demand.
  • Myocardial ischemia is the pathological state underlying ischaemic heart disease.
  • maximizing myocardial salvage from regions of pronounced ischemia in patients suffering an infarction is the most important goal of any therapeutic strategy delivered to the patient.
  • the therapeutic standard for countering the acute ischemic burden is the re-establishment of blood flow, while minimizing ischemia- reperfusion injury, via percutaneous transluminal coronary angioplasty (PTCA) or fibrinolysis.
  • PTCA percutaneous transluminal coronary angioplasty
  • fibrinolysis the most sought after therapeutic regiment is PTCA.
  • reperfusion therapies do not always re-establish flow and can lead to microvascular obstructions (MVOs).
  • MVOs occur at the site of severe ischemic injury and that they have been associated with poor prognosis and reduced survival rates in the months and years post reperfusion. It is also known that MVOs are associated with larger infarcts and that larger infarcts lead to poorer remodeling in the chronic stage of disease culminating in heart failure. Since heart failure is a growing epidemic in the Western World, and most heart failures have origins in ischemic heart disease it is desirable to minimize ischemia-reperfusion injury in right at the acute setting.
  • the invention is directed to a method for reducing microvascular obstructions in a subject in need thereof comprising establishing therapeutic hypothermia by cooling blood prior to reperfusion and performing an angioplasty to re-establish perfusion to an ischemic area in the subject using the cooled blood so as to reduce microvascular obstruction, thereby reducing microvascular obstructions in a subject in need thereof.
  • the subject is a myocardial infarction patient whose treatment is initiated at least 6 hours after the onset of symptoms of myocardial infarction.
  • the method further comprises monitoring microvascular obstructions using magnetic resonance imaging during reperfusion and post reperfusion.
  • the invention is also directed to a method for reducing hemorrhagic microvascular obstructions in a subject in need thereof comprising establishing therapeutic hypothermia by cooling blood prior to reperfusion and performing an angioplasty to re-establish perfusion to an ischemic area in the subject using the cooled blood, so as to reduce hemorrhagic microvascular obstruction, thereby reducing hemorrhagic microvascular obstructions in a subject in need thereof.
  • the subject is a myocardial infarction patient whose treatment is initiated at least 6 hours after the onset of symptoms of myocardial infarction.
  • the method further comprises monitoring microvascular obstructions using magnetic resonance imaging during reperfusion and post-reperfusion.
  • the invention further provides a method for reducing ischemia-reperfusion injury in a subject in need thereof comprising establishing therapeutic hypothermia by cooling blood prior to reperfusion and performing an angioplasty to re-establish perfusion to an ischemic area in the subject using the cooled blood, so as to reduce ischemia-reperfusion injury, thereby reducing ischemia-reperfusion injury in a subject in need thereof.
  • the subject is a myocardial infarction patient whose treatment is initiated at least 6 hours after the onset of symptoms of myocardial infarction.
  • the method further comprises monitoring microvascular obstructions using magnetic resonance imaging during reperfusion and post-reperfusion.
  • “Beneficial results” may include, but are in no way limited to, lessening or alleviating the severity of the disease condition, preventing the disease condition from worsening, curing the disease condition, preventing the disease condition from developing, lowering the chances of a patient developing the disease condition and prolonging a patient's life or life expectancy.
  • “Mammal” or “subject” as used herein refers to any member of the class Mammalia, including, without limitation, humans and nonhuman primates such as chimpanzees and other apes and monkey species; farm animals such as cattle, sheep, pigs, goats and horses; domestic mammals such as dogs and cats; laboratory animals including rodents such as mice, rats and guinea pigs, and the like.
  • the term does not denote a particular age or sex. Thus, adult and newborn subjects, as well as fetuses, whether male or female, are intended to be included within the scope of this term.
  • Treatment and “treating,” as used herein refer to both therapeutic treatment and prophylactic or preventative measures, wherein the object is to prevent or slow down (lessen) the targeted pathologic condition, prevent the pathologic condition, pursue or obtain beneficial results, or lower the chances of the individual developing the condition even if the treatment is ultimately unsuccessful.
  • Those in need of treatment include those already with the condition as well as those prone to have the condition or those in whom the condition is to be prevented.
  • Ischaemia” or “Ischemia” as used herein refers to reduced blood supply to a tissue and/or an organ.
  • Ischemic heart disease refers to reduced blood supply to the heart due to a partial or complete blockage of an artery that carries blood to the heart.
  • Reperfusion as used herein the re-establishing perfusion to an ischemic area and/or organ.
  • “Therapeutic hypothermia” or “therapeutic cooling” as used herein refers to reestablishing perfusion to an ischemic area in a subject using the cooled blood, so as to reduce microvascular obstruction.
  • the blood may be cooled to 2-7°C lower than the normal systemic temperature prior to or during reperfusion.
  • therapeutic hypothermia may be established via surface cooling (wherein the body is cooled by 2-5 degrees centigrade from the baseline level or via the use of a catheter inserted through the femoral artery.
  • “Pain to balloon time” as used herein refers to the time between the onset of symptoms of myocardial infarction up to the angioplasty.
  • One strategy for reducing ischemia-reperfusion injury may be therapeutic hypothermia (re-establish perfusion with blood cooled to, for example, 2-7°C lower than the normal systemic temperature), particularly in myocardial infarction patients whose treatment is initiated, for example, at least 2 hours, 3 hours, at least 4 hours, at least 5 hours or at least 6 hours, after the onset of symptoms of myocardial infarction.
  • therapeutic hypothermia re-establish perfusion with blood cooled to, for example, 2-7°C lower than the normal systemic temperature
  • the inventor proposes the use of therapeutic cooling in candidate patients outside the therapeutic window (for example, pain to balloon time of about 5 hours or more, i.e. patients whose treatment is initiated about 5 hours or more after the onset of symptoms of myocardial infarction) combined with magnetic resonance imaging to monitor the extent of microvascular obstructions. Specifically, the longer the pain to balloon time the larger and/or more severe the microvascular obstructions.
  • the inventor also hypothesizes that it is not only the MVOs that lead to poor prognosis but the more severe form of MVOs, which also lead to intramyocardial hemorrhage and that it is this intramyocardial hemorrhage that can accelerate oxidative stress in the ischemic myocardium.
  • Therapeutic cooling may reduce MVOs and thereby reduce intramyocardial hemorrhage and improve prognosis. The extent of the MVOs and intramyocardial hemorrhage may be fully evaluated on the basis of MRI.
  • the invention is directed to a method for reducing microvascular obstructions in a subject in need thereof comprising establishing therapeutic hypothermia by cooling blood prior to reperfusion and performing an angioplasty to re-establish perfusion ("reperfusion") to an ischemic area in the subject using the cooled blood, so as to reduce microvascular obstruction, thereby reducing microvascular obstructions in a subject in need thereof.
  • reperfusion may be established using fibrinolytic therapy.
  • reperfusion may be established using both, angioplasty and fibrinolytic therapy.
  • the method further comprises monitoring microvascular obstructions using magnetic resonance imaging during reperfusion and post-reperfusion (for example, during the acute (for example 1-3 days) up to sub-acute (for example 1-2 weeks) phases post reperfusion).
  • the cooled blood may be reperfused for about 2 hours prior to switching to normothermic (normal temperature) perfusion (for example at the termination of the angioplasty).
  • the subject is a myocardial infarction patient whose treatment is initiated at least 2 hours, at least 3 hours, at least 4 hours, at least 5 hours or at least 6 hours after the onset of symptoms of myocardial infarction.
  • Hemorrhaging is associated with microvascular obstructions.
  • the invention is also directed to a method for reducing hemorrhagic microvascular obstructions in a subject in need thereof comprising establishing therapeutic hypothermia by cooling blood prior to reperfusion and performing an angioplasty to re-establish perfusion to an ischemic area in the subject using the cooled blood, so as to reduce hemorrhagic microvascular obstruction, thereby reducing hemorrhagic microvascular obstructions in a subject in need thereof.
  • reperfusion may be established using fibrinolytic therapy.
  • reperfusion may be established using both, angioplasty and fibrinolytic therapy.
  • the method further comprises monitoring microvascular obstructions using magnetic resonance imaging during reperfusion and post-reperfusion (for example, during the acute (for example 1-3 days) up to sub-acute (for example 1-2 weeks) phases post reperfusion).
  • the cooled blood may be reperfused for about 2 hours prior to switching to normothermic perfusion (for example at the termination of the angioplasty).
  • the subject is a myocardial infarction patient whose treatment is initiated at least 2 hours, at least 3, at least 4, at least 5 or at least 6 hours after the onset of symptoms of myocardial infarction.
  • Intramyocardial hemorrhaging may occur in non-reperfused infarction as well as in reperfused infarctions. Therefore, therapeutic hypothermia may be used to prevent and/or reduce myocardial hemorrhage. Accordingly, invention provides methods for reducing hemorrhagic microvascular obstructions in a subject in need thereof wherein the subject has not and/or will no undergo reperfusion therapy.
  • the subject may be a patient for whom reperfusion therapy is not indicated based on the American Heart Association (AHA) guidelines.
  • AHA American Heart Association
  • the method comprises establishing therapeutic hypothermia so as to cool the blood in a subject and monitoring microvascular obstructions and/or decreased burden of hemorrhaging using imaging method including magnetic resonance imaging, for at least 1-2 days, at least 2-3 days, at least 3-4 days, at least 4-5 days, at least 5-6 days, at least 6-7 days, at least 7-8 days, at least 8-9 days and/or at least 9-10 days post therapy.
  • therapeutic hypothermia is established using surface cooling wherein the patient is cooled for at least 1 hour, at least 2 hours, at least 3 hours, at least 4 hours, at least 5 hours, at least 6 hours, at least 7 hours or at least 8 hours.
  • therapeutic hypothermia is established using a catheter inserted through the femoral artery to cool the circulating blood.
  • the invention further provides a method for reducing ischemia-reperfusion injury in a subject in need thereof comprising establishing therapeutic hypothermia by cooling blood prior to reperfusion and performing an angioplasty to re-establish perfusion to an ischemic area in the subject using the cooled blood, so as to reduce ischemia-reperfusion injury, thereby reducing ischemia-reperfusion injury in a subject in need thereof.
  • reperfusion may be established using fibrinolytic therapy.
  • reperfusion may be established using both, angioplasty and fibrinolytic therapy.
  • the method further comprises monitoring microvascular obstructions using magnetic resonance imaging during reperfusion and post-reperfusion (for example, during the acute (for example 1-3 days) up to sub-acute (for example 1-2 weeks) phases post reperfusion).
  • the cooled blood may be reperfused for about 2 hours prior to switching to normothermic perfusion (for example at the termination of the angioplasty).
  • the subject is a myocardial infarction patient whose treatment is initiated at least 2 hours, at least 3, at least 4, at least 5 or at least 6 hours after the onset of symptoms of myocardial infarction
  • blood is cooled to 2-7°C lower than the normal systemic temperature.
  • the blood may be cooled with endovascular or surface cooling approaches using Thermogard XP Temperature Management System (Zoll Medical, Chelmsford, MA, USA) or the RTx Endovascular System, STx Surface Pad System, combined with Accutrol Catheter by Philips (Andover, MA, USA), and other similar devices.
  • the claimed methods further comprise monitoring microvascular obstructions using magnetic resonance imaging during reperfusion and post-reperfusion (for example, during the acute (for example 1-3 days) up to sub-acute (for example 1-2 weeks) phases post reperfusion).
  • the claimed methods are directed to performing therapeutic hypothermia in patients whose treatment is initiated outside the therapeutic window, specifically, in patients whose treatment is initiated at least 2 hours, at least 3 hours, at least 4 hours, at least 5 hours or at least 6 hours after the onset of the symptoms of myocardial infarction.
  • therapeutic hypothermia is performed in patients whose treatment is initiated at least 4 hours or at least 5 hours after the onset of symptoms of myocardial infarction.
  • the therapeutic hypothermia is performed in patients whose treatment is initiated at least 6 hours after the onset of symptoms of myocardial infarction.
  • symptoms of myocardial infarction include but are not limited to any one or more of chest pain, elevated FP segment in an electrocardiogram (ECG) and/or elevated troponin levels in the blood.
  • Chest pains may be accompanied by shortness of breath, dizziness or lightheadedness, jaw pain, nausea/vomiting, unusual fatigue, cold sweat and/or pain in the arm, back, neck, abdomen, and or shoulder blades.
  • This data may serve as controls in our studies.
  • the inventor will collect other control data where reperfusion is done rapidly ( ⁇ 30 minutes) from the time of induction of severe ischemia.
  • the inventor will also study similar number of animals subjected to later reperfusion injury and therapeutic hypothermia during reperfusion to demonstrate that hemorrhagic MVOs can be significantly reduced.
  • an RTx endo vascular system by Philips may be used.
  • Tl -weighted scans often utilized in conjunction with the infusion of an exogenous contrast media (gadolinium chelates), is the standard for identifying infarcted territories within the heart muscle.
  • the first-passage of the contrast media can be used to identify perfusion deficit territories (such as those from microvascular obstruction) as regions of hypointensities within the myocardium.
  • Short delay following the administration of the contrast media can also be used to gather information on microvascular obstruction should the first passage of the contrast agent not provide adequate coverage of the left ventricular mass.
  • regions of MVOs also appear as hypointense regions.
  • late-enhancement images typically acquired 10-15 minutes after the administration of the contrast agent
  • Persistent MVOs are understood to be myocardial territories that are significantly impaired by MVOs. In addition to these scans, either pre- or post-contrast administration, it is possible to identify territories of myocardial hemorrhage with T2* -weighted cardiac MR scans.
  • T2* images are specific for identifying the degradation products of red blood cells hence the Tl -weighted and T2* images can be evaluated together to quantify the regional extent of necrosis, MVOs, and hemorrhagic.
  • T2* images may be used to identify hemorrhage in acute reperfused myocardial infarction with MRI.
  • Candidate subjects are identified to undergo reperfusion therapy (percutaneous coronary intervention (PCI) or fibrinolytic therapy) by establishing therapeutic hypothermia by cooling blood prior to reperfusion.
  • PCI percutaneous coronary intervention
  • fibrinolytic therapy percutaneous coronary intervention
  • blood is cooled with the help of surface cooling or endovascular cooling systems to 2-7 degrees Celsius below core body temperature first and then reperfusion is started.
  • the cooled blood can be reperfused by a standard procedure by opening up the collapsed vessel and leaving it open with the aid of a stent or modulating the rate delivery of the cooled blood by slowly vascularizing the obstructed artery to full patency or by more advanced approaches where the reperfusion is punctuated by periods of no or reduced flow (for instance via post-conditioning approaches).
  • This intervention can be done in a cardiac catheterization laboratory under X-ray fluorescence or under XMR systems, where X-ray and MR acquisition are used in an interleaved fashion to assess the effectiveness of reperfusion at the time of intervention. If the procedure is performed only under X-ray guidance (most common), the subject may be brought back to MR imaging in the acute or sub-acute period following reperfusion and cardiac MR acquisitions are performed to assess myocardial function (wall motion via myocardial tagging), volumetric indices (ejection fraction, end-diastolic volume, end-systolic volume etc via cine imaging), tissue characterization (edema (via Tl, T2, magnetization transfer, or SSFP imaging), MVO (first pass imaging, early enhancement imaging, late gadolinium enhancement imaging), hemorrhage (Tl, T2, or T2* imaging), fibrosis (Tl imaging), perfusion (first pass imaging), necrosis (late gadolinium enhancement imaging), and coronary angiography
  • MR computed tomography
  • surface and/or endovascular cooling may be used. If the procedure is performed only under X-ray guidance (most common), the subject may be brought back to MR imaging in the acute or sub-acute period following reperfusion and cardiac MR acquisitions are performed to assess myocardial function (wall motion via myocardial tagging), volumetric indices (ejection fraction, end- diastolic volume, end-systolic volume etc via cine imaging), tissue characterization (edema (via Tl, T2, magnetization transfer, or SSFP imaging), MVO (first pass imaging, early enhancement imaging, late gadolinium enhancement imaging), hemorrhage (Tl, T2, or T2* imaging), fibrosis (Tl imaging), perfusion (first pass imaging), necrosis (late gadolinium enhancement imaging), and coronary angiography (with or without contrast media).
  • myocardial function wall motion via myocardial tagging
  • volumetric indices ejection fraction, end- diastolic volume, end-sy
  • MR computed tomography
  • surface and/or endovascular cooling may be used. If the procedure is performed only under X-ray guidance (most common), the subject may be brought back to MR imaging in the acute or sub-acute period following reperfusion and cardiac MR acquisitions are performed to assess myocardial function (wall motion via myocardial tagging), volumetric indices (ejection fraction, end-diastolic volume, end- systolic volume etc via cine imaging), tissue characterization (edema (via Tl, T2, magnetization transfer, or SSFP imaging), MVO (first pass imaging, early enhancement imaging, late gadolinium enhancement imaging), hemorrhage (Tl, T2, or T2* imaging), fibrosis (Tl imaging), perfusion (first pass imaging), necrosis (late gadolinium enhancement imaging), and coronary angiography (with or without contrast media).
  • myocardial function wall motion via myocardial tagging
  • volumetric indices ejection fraction, end-diastolic volume, end
  • MR computed tomography
  • the invention also provides method for monitoring the course of microvascular obstruction in a subject comprising providing a subject in need of reduction and/or inhibition of microvascular obstruction, establishing therapeutic hypothermia by cooling blood prior to reperfusion, re-establishing reperfusion to an ischemic area and monitoring microvascular obstructions using magnetic resonance imaging during reperfusion. Contrast-enahnced MRI delineating slow filling territories identified on early- enhancement, late-enhancement and non-contrast enhanced T2 and T2* weighted imaging may be used for MVOs and severe MVOs associated with myocardial hemorrhage.

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Abstract

L'invention porte sur des procédés pour réduire des obstructions microvasculaires, réduire des obstructions microvasculaires hémorragiques et/ou réduire une lésion due à une reperfusion consécutivement à une ischémie chez un sujet en ayant besoin par utilisation d'une hypothermie thérapeutique et surveillance du résultat de l'intervention avec une norme d'imagerie non invasive.
PCT/US2012/035307 2011-04-29 2012-04-26 Caractérisation à base d'imagerie par résonance magnétique (irm) d'une obstruction microvasculaire en réponse à une hypothermie thérapeutique après un infarctus aigu du myocarde Ceased WO2012149226A2 (fr)

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2015021078A1 (fr) * 2013-08-05 2015-02-12 Cedars-Sinai Medical Center Méthodes de réduction de lésion de reperfusion d'ischémie

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US20040167467A1 (en) * 2003-02-21 2004-08-26 Kent Harrison Delivering cooled fluid to sites inside the body
US20070014764A1 (en) * 2005-07-18 2007-01-18 Andrew Levy Reduction in myocardial infarction size
EP2073884B1 (fr) * 2006-08-02 2018-10-10 Osprey Medical Inc. Détection d'une obstruction microvasculaire et thérapie correspondante
US8870847B2 (en) * 2007-11-27 2014-10-28 Abbott Cardiovascular Systems Inc. Blood vessel permeability-enhancement for the treatment of vascular diseases

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2015021078A1 (fr) * 2013-08-05 2015-02-12 Cedars-Sinai Medical Center Méthodes de réduction de lésion de reperfusion d'ischémie
US10471094B2 (en) 2013-08-05 2019-11-12 Cedars-Sinai Medical Center Methods for reducing ischemia-reperfusion injury via targeted control of blood gases

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