WO2015034951A1 - Viabilité myocardique par irm sans milieu de contraste exogène - Google Patents

Viabilité myocardique par irm sans milieu de contraste exogène Download PDF

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WO2015034951A1
WO2015034951A1 PCT/US2014/053938 US2014053938W WO2015034951A1 WO 2015034951 A1 WO2015034951 A1 WO 2015034951A1 US 2014053938 W US2014053938 W US 2014053938W WO 2015034951 A1 WO2015034951 A1 WO 2015034951A1
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images
maps
tesla
lge
transmurality
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Rohan Dharmakumar
Kali AVINASH
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Cedars-Sinai Medical Center
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    • 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
    • G01R33/50—NMR imaging systems based on the determination of relaxation times, e.g. T1 measurement by IR sequences; T2 measurement by multiple-echo sequences
    • 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 classified in A61B5/00, 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 classified in A61B5/00, 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 classified in A61B5/00, 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
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B2505/00—Evaluating, monitoring or diagnosing in the context of a particular type of medical care
    • A61B2505/03—Intensive care
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/24—Detecting, measuring or recording bioelectric or biomagnetic signals of the body or parts thereof
    • A61B5/316—Modalities, i.e. specific diagnostic methods
    • A61B5/318—Heart-related electrical modalities, e.g. electrocardiography [ECG]
    • A61B5/346—Analysis of electrocardiograms
    • A61B5/349—Detecting specific parameters of the electrocardiograph cycle
    • 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
    • G01R33/56308—Characterization of motion or flow; Dynamic imaging

Definitions

  • the invention provides methods for characterizing a myocardial infarction using magnetic resonance imaging, without the use of contrast agents.
  • LGE Late Gadolinium Enhancement
  • Contrast-enhanced Tl mapping has been proposed as a potential technique that could overcome some of the problems faced by LGE imaging. Since Tl mapping measures the absolute Tl values instead of the arbitrary signal intensities, Tl imaging approach can be powerful for serial evaluation of tissue-specific changes during longitudinal studies. Contrast- enhanced Tl mapping also eliminates the need for effective nulling of the remote myocardium faced by LGE imaging. Nevertheless, like LGE imaging, the Tl value of infarcted myocardium in contrast-enhanced Tl mapping depends on the gadolinium kinetics.
  • contrast-enhanced imaging is deemed necessary for assessment of myocardial viability, all other imaging sequences are typically required to be prescribed ahead of LGE imaging, which could impose practical limitations on the execution of the imaging exam, especially when rapid assessment of viability is required.
  • contrast- enhanced imaging requires administration of a gadolinium chelate, which is contraindicated in patients with renal insufficiency.
  • Non-contrast Tl mapping by definition does not require exogenous contrast media. Therefore, the technique can be safely used even in patients for whom LGE imaging and contrast-enhanced Tl mapping are contraindicated.
  • Recent studies have shown that non- contrast Tl mapping can reliably detect acute myocardial infarction at both 1.5T and 3T.
  • the diagnostic performance of non-contrast Tl mapping to detect chronic myocardial infarction has been shown to be poor at 1.5T.
  • native Tl mapping at 3T has been shown to detect diffuse myocardial fibrosis in non-ischemic cardiomyopathies, the ability of the technique to detect replacement fibrosis in chronic myocardial infarctions at 3T has not been previously shown.
  • non-contrast Tl mapping at 3T can be used to reliably detect and quantify replacement myocardial fibrosis associated with chronic myocardial infarction.
  • a method comprising providing a subject having or suspected of having a myocardial infarction; prescribing any one or more of Tl -mapping, Tl -weighted imaging, inversion-recovery prepared Tl -weighted imaging or a combination thereof and obtaining one or more magnetic resonance images; prescribing any one or more of T2- weighted images, T2 maps, T2* -weighted images, T2* maps, diffusion weighted images, apparent-diffusion-coefficient (ADC) maps, steady-state free precession CINE images, steady-state free precession non-CINE images, steady-state free precession coherent images, incoherent steady-state free precession images, myocardial tags, magnetization transfer (MT) weighted and MT rate (MTR) images, or a combination thereof; and obtaining one or more Tl and T2 magnetic resonance (MR) images, wherein the subject has not been administered a contrast agent.
  • MR images are examples of Tl and T2 magnetic resonance (
  • the method includes providing a subject having or suspected of having a myocardial infarction; prescribing any one or more of Tl -mapping imaging, Tl- weighted mapping, inversion-recovery prepared Tl -weighted imaging or a combination thereof and obtaining one or more magnetic resonance images; prescribing any one or more of T2-weighted images, T2 maps, T2* -weighted images, T2* maps, diffusion weighted images, apparent-diffusion-coefficient (ADC) maps, steady-state free precession CINE images, steady-state free precession non-CINE images, steady-state free precession coherent images, incoherent steady-state free precession images, myocardial tags, magnetization transfer images, or a combination thereof; and obtaining one or more Tl and T2 magnetic resonance (MR) images, wherein the subject has not been administered a contrast agent.
  • Tl -mapping imaging Tl- weighted mapping, inversion-recovery prepared Tl -weighted
  • any one or more of is indicative of a chronic myocardial infarction.
  • MR images are obtained at a magnetic field strength of 3.0 Tesla or greater.
  • Figure 1 depicts, in accordance with various embodiments of the present invention, detection of acute myocardial infarction at 3T.
  • Representative LGE images and Tl maps of basal, mid-ventricular and apical slices acquired at 7 days post reperfusion from a canine scanned at 3T are shown.
  • Infarcted myocardium black arrows pointing to the highlighted pixels in the processed images
  • Mean+5SD Standard Deviation
  • ROI Region of Interest
  • Bulls- eye plots depicting the extent and transmurality of the infarcted myocardium are also shown for both LGE images and Tl maps.
  • the number in each segment indicates the percentage volume of that segment that was detected as infarcted myocardium by the Mean+5SD criterion.
  • each slice was divided into 100 equally spaced chords with the first chord placed at the anterior insertion of the RV into the LV.
  • Each concentric ring on the Bulls-eye plot represents each short-axis slice with the most basal slice represented by the outermost ring.
  • LGE images and Tl maps correlated well in terms of the location of the infarct.
  • FIG. 2 depicts, in accordance with various embodiments of the present invention, diagnostic performance of non-contrast Tl maps for detecting acute myocardial infarction at 3T.
  • Bland-Altman analysis showed good agreement between LGE images and Tl maps acquired for measuring infarct size (A) and transmurality (B) during the acute phase at 3T.
  • Tl maps modestly overestimated infarct size and transmurality compared to LGE images.
  • ROC analysis showed that area under the curve was 0.96 (E) indicating a strong diagnostic performance of non-contrast Tl maps for detecting acute myocardial infarction at 3T.
  • Figure 3 depicts, in accordance with various embodiments of the present invention, detection of chronic myocardial infarction at 3T.
  • Representative LGE images and Tl maps of basal, mid-ventricular and apical slices acquired at 4 months post reperfusion from a canine scanned at 3T are shown.
  • Infarcted myocardium black arrows pointing to the highlighted pixels in the processed images
  • Mean+5SD criterion was identified on both LGE images and Tl maps using Mean+5SD criterion with respect to the reference ROI drawn in remote myocardium.
  • Hypointense core of chronic iron deposition within the hyperintense infarcted myocardium was not detected as infarcted myocardium by the Mean+5SD criterion, and was manually included in the final analysis (white arrow pointing to the lighter pixels within the infarcted core on the processed images).
  • Figure 4 depicts, in accordance with various embodiments of the present invention, diagnostic performance of non-contrast Tl maps for detecting chronic myocardial infarction at 3T.
  • Bland- Altman analysis showed excellent agreement between LGE images and Tl maps for measuring infarct size (A) and transmurality (B) during the chronic phase at 3T.
  • ROC analysis showed that area under the curve was 0.99 (Figure 4E) indicating an excellent diagnostic performance by non- contrast Tl maps for detecting chronic myocardial infarction at 3T.
  • FIG. 5 depicts, in accordance with various embodiments of the present invention, detection of acute myocardial infarction at 1.5T.
  • Representative LGE images and Tl maps of basal, mid-ventricular and apical slices acquired at 7 days post reperfusion from a canine scanned at 1.5T are shown.
  • Infarcted myocardium black arrows pointing to the highlighted pixels in the processed images
  • Mean+5SD criterion was identified on both LGE images and Tl maps using Mean+5SD criterion.
  • Good correlation was observed between LGE images and the Tl maps in terms of location of the infarcted myocardium.
  • the extent of infarcted myocardium and transmurality were, however, significantly underestimated by the Tl maps relative to the LGE images (p ⁇ 0.001 for both cases).
  • Figure 6 depicts, in accordance with various embodiments of the present invention, diagnostic performance of non-contrast Tl maps for detecting acute myocardial infarction at 1.5T.
  • Bland- Altman analysis showed moderate agreement between LGE images and Tl maps for measuring infarct size (Figure 7 A) and transmurality (Figure 7B) using the Mean + 5SD criterion at 1.5T during the acute phase.
  • Tl maps significantly underestimated infarct size and transmurality compared to LGE images.
  • ROC analysis showed that area under the curve was 0.86 (E) indicating a moderate diagnostic performance by non-contrast Tl maps for detecting acute myocardial infarction at 1.5T.
  • FIG. 7 depicts, in accordance with various embodiments of the present invention, detection of chronic myocardial infarction at 1.5T.
  • Representative LGE images and Tl maps of basal, mid-ventricular and apical slices acquired at 4 months post reperfusion from a canine scanned at 1.5T are shown.
  • the LGE image and Tl map are poorly correlated in terms of the spatial extent and location of the infarcted myocardium.
  • Tl hyperintensity observed in the apical slice was possibly due to partial volume effects. Bulls-eye plots showed significant underestimation of infarct size and transmurality on Tl maps relative to LGE images (p ⁇ 0.001 for both cases).
  • Figure 8 depicts, in accordance with various embodiments of the present invention, diagnostic performance of non-contrast Tl maps for detecting chronic myocardial infarction at 3T.
  • Bland- Altman analysis showed poor agreement between LGE images and Tl maps for measuring infarct size (A) and transmurality (B) during the chronic phase at 1.5T.
  • Tl maps greatly underestimated infarct size and transmurality compared to LGE images.
  • ROC analysis showed that area under the curve was 0.79 (Figure 9E) indicating a poor diagnostic performance by Tl maps for detecting chronic myocardial infarction at 1.5T.
  • FIG 9 depicts, in accordance with various embodiments of the present invention, Tl and T2 characteristics of infarcted myocardium at 1.5T and 3T during the acute and chronic phases of infarction.
  • Representative LGE images, Tl maps and T2 maps acquired at 1.5T and 3T from four different canines at 7 days and 4 months post reperfusion are shown. Arrows point to the sites of LGE, Tl and T2 hyperintensities.
  • Significant Tl and T2 elevations were visually evident within the infarcted territories in the acute phase of infarction at 3T. While Tl elevations persisted at 4 months post reperfusion at 3T, T2 of the infarcted myocardium returned to baseline levels.
  • Tl and T2 of infarcted myocardium were significantly elevated during the acute phase of infarctions.
  • both Tl and T2 values of the infarcted myocardium were not visually contrasting from those of remote myocardium during the chronic phase of infarction at 1.5T.
  • Color scales used for Tl maps are the same as those shown in figures 1 and 3.
  • FIG. 10 depicts, in accordance with various embodiments of the present invention, histopatho logical validation of replacement fibrosis detected on LGE images and Tl maps during the chronic phase of infarction at 3T.
  • Representative LGE images and Tl maps acquired from three different canines scanned at 3T at 4 months post reperfusion are shown along with the corresponding ex-vivo slice-matched Triphenyl Tetrazolium Chloride (TTC) images and Elastin Masson's Trichrome (EMT) staining images.
  • TTC Triphenyl Tetrazolium Chloride
  • EMT Elastin Masson's Trichrome
  • TTC image shows a dark discoloration in the necrotic core indicating the presence of iron.
  • Additional histological validation using EMT staining confirmed extensive replacement fibrosis within the infarcted regions indicating that Tl hyperintensity in the chronic phase of infarction at 3T predominantly arose from fibrosis.
  • Tl scales used for the Tl maps are the same as those shown in Figures 1 and 3.
  • Figure 11 depicts, in accordance with various embodiments of the present invention, amplification of relative image contrast in a Tl phantom with IR-bSSFP (Inversion Recovery balanced Steady-State Free Precession).
  • Figure 12 depicts, in accordance with various embodiments of the present invention, amplification of image contrast to improve visualization of chronic MI with IR-bSSFP. With IR-bSSFP even a small MI is readily visible. CNR values in parenthesis were from 6 averages.
  • Figure 13 depicts, in accordance with various embodiments of the present invention, characterization of chronic MI at 3T.
  • Typical short-axis LGE images and contrast-agent-free bSSFP-Tl maps from a canine with chronic MI at 3T are shown.
  • MI black arrows pointing to the highlighted pixels in the processed images
  • Bulls-eye plots depicting the size and transmurality of the MI are shown for both LGE and TV Excellent correlations were observed between LGE images and bSSFP-Ti maps in terms of the location, spatial extent and transmurality of the infarcted myocardium.
  • Native Tl mapping has been shown to be able to detect acute myocardial infarction at both 1.5T and 3T.
  • the only study that evaluated native Tl mapping to detect chronic myocardial infarctions used 1.5T magnetic field strength and showed that the technique has poor diagnostic performance.
  • native Tl mapping will be able to detect chronic myocardial infarctions when the field strength is increased from 1.5T to 3T.
  • diffuse myocardial fibrosis in non-ischemic cardiomyopathies has been shown to be detected well using native Tl mapping at 3T.
  • the ability of the technique to detect replacement fibrosis in chronic myocardial infarctions is unknown to date.
  • the inventors were the first to show that native Tl mapping when used at 3T can accurately detect and characterize chronic myocardial infarctions. Although the mechanistic underpinnings need to be fully explored, longer native Tl values at 3T relative to 1.5T could be one possible mechanism. Another possible mechanism is the decreased magnetization transfer (MT) effect in infarcted myocardium relative to viable/remote myocardium, which can further augment the infarcted-to-remote myocardium contrast. MT -based contrast is further enhanced when the field strength is increased from 1.5T to 3T.
  • the novel finding herein is that increasing the field strength from 1.5T to 3T will significantly improve the diagnostic accuracy of native Tl mapping for detecting chronic myocardial infarctions.
  • the diagnostic accuracy of native Tl mapping at 3T is comparable to that of LGE imaging, which is currently the gold-standard technique.
  • the inventors used the Mean+SSD segmentation method to detect the infarcted myocardium on native Tl maps.
  • the clinician should be able to visually identify the infarct on native Tl maps. This requires a higher infarcted-to-remote myocardium contrast than that achieved by native Tl mapping. Therefore, we sought to further improve the infarcted-to-remote myocardium seen on native Tl maps.
  • the inventors have used two schemes thai- will further enhance the contrast at 3T: (i) the inventors have harnessed the inherent native Tl differences between infarcted and remote myocardium using an inversion-recovery (IR) scheme that will adequately null any signal arising only from the remote myocardium; and (ii) the inventors have used an SSFP readout that is sensitive to MT effects and will therefore enhance the contrast by harnessing the MT difference between infarcted and remote myocardium.
  • IR inversion-recovery
  • the inventors showed that the IR-SSFP technique had higher infarct-to-remote contrast compared to that of native Tl maps.
  • the proposed IR-SSFP technique is also able to detect chronic myocardial infarctions. Moreover, it has higher infarcted-to-remote myocardium contrast compared to native TT maps. The increased contrast can potentially aid clinicians in visually identifying the infarcted myocardium on IR-SSFP images.
  • Both native Tl mapping and IR-SSFP techniques at 3T can detect chronic myocardial infarctions without the need for any exogenous contrast agent such as gadolinium. These techniques can be potentially applied to patients with chronic myocardial infarction, but are contraindicated to gadolinium contrast, and therefore LGE imaging, due to poor kidney function.
  • a method comprising providing a subject having or suspected of having a myocardial infarction; prescribing any one or more of Tl -mapping imaging, Tl -weighted mapping, inversion-recovery prepared Tl -weighted imaging or a combination thereof and obtaining one or more magnetic resonance images; prescribing any one or more of T2-weighted images, T2 maps, T2* -weighted images, T2* maps, diffusion weighted images, apparent-diffusion-coefficient (ADC) maps, steady-state free precession CINE images, steady-state free precession non-CINE images, steady-state free precession coherent images, incoherent steady-state free precession images, myocardial tags, magnetization transfer (MT) weighted and MT rate (MTR) images, or a combination thereof; and obtaining one or more Tl and T2 magnetic resonance (MR) images, wherein the subject has not been administered a contrast agent.
  • Tl -mapping imaging Tl -weight
  • the method includes providing a subject having or suspected of having a myocardial infarction; prescribing any one or more of Tl -mapping imaging, Tl- weighted mapping, inversion-recovery prepared Tl -weighted imaging or a combination thereof and obtaining one or more magnetic resonance images; prescribing any one or more of T2-weighted images, T2 maps, T2* -weighted images, T2* maps, diffusion weighted images, apparent-diffusion-coefficient (ADC) maps, steady-state free precession CINE images, steady-state free precession non-CINE images, steady-state free precession coherent images, incoherent steady-state free precession images, myocardial tags, magnetization transfer (MT) weighted and MT rate (MTR) images, or a combination thereof; and obtaining one or more Tl and T2 magnetic resonance (MR) images, where
  • any one or more of is indicative of a chronic myocardial infarction.
  • MR images are obtained at a magnetic field strength of 3.0 Tesla or greater.
  • the images are obtained using clinical MRI scanners, PET/MR scanners, small animal MRI scanners or combinations thereof.
  • the myocardial infarction is chronic myocardial infarction.
  • the myocardial infarction is acute myocardial infarction.
  • inversion-recovery prepared Tl -weighted imaging nulls the signal from viable myocardium.
  • the methods described herein further include determining the infarct size in the subject with myocardial infarction.
  • the infarct size may be measured by any one or combination of determining the left ventricular volume after a myocardial infarction and determining the infarct mass.
  • the left ventricular volume and/or the infarct mass may be measured using methods including but not limited to image segmentation methods, manual thresholding, manual contouring or a combination thereof.
  • Image segmentation methods include but are not limited to intensity thresholding methods, full width half maximum methods, Otsu method (also known as automatic thresholding) or combinations thereof.
  • image segmentation may be performed using threshold-based techniques using mean+n standard deviations criteria where n can be 2, 3, 4, 5, 6, 7, 8, 9, 10 or more, as described in Amado LC, et al. Accurate and objective infarct sizing by contrast-enhanced magnetic resonance imaging in a canine myocardial infarction model. J Am Coll Cardiol. 2004;44(12):2383-9; Bondarenko O, et al.
  • image segmentation may be performed using Mean + n standard deviations criteria where n is determined using k-means method, for example as described in Heiberg E, et al. Automated quantification of myocardial infarction from MR images by accounting for partial volume effects: animal, phantom, and human study. Radiology. 2008; 246(2):581-8.
  • image segmentation may be performed using full-width half- maximum technique as described in, for example, Amado LC, et al. Accurate and objective infarct sizing by contrast-enhanced magnetic resonance imaging in a canine myocardial infarction model. J Am Coll Cardiol. 2004;44(12):2383-9; Beek AM, et al. Quantification of late gadolinium enhanced CMR in viability assessment in chronic ischemic heart disease: a comparison to functional outcome. J Cardiovasc Magn Reson. 2009;11 :6. PMCID: 2657135; Flett AS, et al.
  • image segmentation may be performed using signal intensity threshold (also known as manual thresholding) manually set by the observer as described in, for example, Neizel M. et al. Rapid and accurate determination of relative infarct size in humans using contrast-enhanced magnetic resonance imaging. Clin Res Cardiol. 2009; 98(5):319-24.
  • image segmentation may be performed using fast-level set method as described in, for example, Heiberg E, et al. Automated quantification of myocardial infarction from MR images by accounting for partial volume effects: animal, phantom, and human study. Radiology. 2008;246(2):581-8; Heiberg E, et al. Semi-automatic quantification of myocardial infarction from delayed contrast enhanced magnetic resonance imaging. Scand Cardiovasc J. 2005; 39(5):267-75.
  • image segmentation may be performed using Feature Analysis and Combined Thresholding (FACT) method as described in, for example, Hsu LY, et al. Quantitative myocardial infarction on delayed enhancement MRI.
  • FACT Feature Analysis and Combined Thresholding
  • Part II Clinical application of an automated feature analysis and combined thresholding infarct sizing algorithm. J Magn Reson Imaging. 2006; 23(3):309-14; Hsu LY, et al. Quantitative myocardial infarction on delayed enhancement MRI.
  • Part I Animal validation of an automated feature analysis and combined thresholding infarct sizing algorithm. J Magn Reson Imaging. 2006;23(3):298-308.
  • image segmentation may be performed using the Otsu methods as described in, for example, Vermes E, et al. Auto-threshold quantification of late gadolinium enhancement in patients with acute heart disease. J Magn Reson Imaging. 2013; 37(2):382- 90.
  • image segmentation may be performed using manual planimetry using visual assessment as described in, for example, Amado LC, et al. Accurate and objective infarct sizing by contrast-enhanced magnetic resonance imaging in a canine myocardial infarction model. J Am Coll Cardiol. 2004;44(12):2383-9; Bondarenko O, et al. Standardizing the definition of hyperenhancement in the quantitative assessment of infarct size and myocardial viability using delayed contrast-enhanced CMR. J Cardiovasc Magn Reson. 2005;7(2):481-5; Flett AS, et al.
  • Cardiac magnetic resonance imaging long term reproducibility of the late enhancement signal in patients with chronic coronary artery disease. Heart. 2005;91(9): 1158-63.
  • PMCID 1769072; Thiele H, et al. Reproducibility of chronic and acute infarct size measurement by delayed enhancement- magnetic resonance imaging. J Am Coll Cardiol. 2006;47(8): 1641-5.
  • image segmentation may be performed using the Otsu method.
  • the Otsu method is a user independent technique that automatically segments the infarcted myocardium.
  • the technique separates the pixels into infarcted myocardium from remote myocardium by minimizing the intraclass variance between the two regions (Otsu N.
  • a threshold selection method from graylevel histograms. IEEE Transactions on Systems, Man and Cybernetics, 1979, 9(1): 62-66; Vermes E, Childs H, Carbone I, Barckow P, Friedrich M G. Auto-threshold quantification of late gadolinium enhancement in patients with acute heart disease. Journal of Magnetic Resonance Imaging, 2013, 37(2): 382-390).
  • the left ventricular volume and/or the infarct mass may be measured using manual contouring.
  • Manual contouring is a technique in which the user visually identifies the infarcted myocardium on the images and manually traces the border of the infarcted myocardium (Amado L C, et al. Accurate and objective infarct size by contrast- enhanced magnetic resonance imaging in a canine myocardial infarction model. Journal of the American College of Cardiology, 2004, 44(12): 2383-2389; Bondarenko O. et al. Standardizing the definition of hyperenhancement in the quantitative assessment of infarct size and myocardial viability using delayed contrast-enhanced CMR.
  • Chronic myocardial infarction, or healed myocardial infarction, or prior myocardial infarction is defined by the third universal definition of myocardial infarction (Thygesen K, et al. Third universal definition of myocardial infarction. Journal of the American College of Cardiology. 2012;60(16): 1581-98. PubMed PMID: 22958960.).
  • any one of the following criteria satisfies the diagnosis for chronic myocardial infarction: (i) pathologic Q waves (>0.04 sec) with or without symptoms in the absence of non-ischemic causes; (ii) pathologic findings of a healed or healing MI and/or (iii) evidence from an imaging study of a region of loss of viable myocardium that is thinned and fails to contract in the absence of a nonischemic cause.
  • the method further includes determining the location of the infarction in the subject.
  • the location may be determined using AHA segmentation models, centerline chord methods or combinations thereof.
  • AHA segmentation models may be obtained using methods described in, for example, Cerqueira MD, et al. Standardized myocardial segmentation and nomenclature for tomographic imaging of the heart. A statement for healthcare professionals from the Cardiac Imaging Committee of the Council on Clinical Cardiology of the American Heart Association. Circulation. 2002; 105(4):539-42.
  • centerline chord methods may be performed using methods described in, for example, Sheehan FH et al. Advantages and applications of the centerline method for characterizing regional ventricular function. Circulation. 1986; 74(2):293-305.
  • the method further includes determining the transmurality of the myocardial infarction in the subject.
  • transmurality of the infarction may be determined using segmental area-based methods, centerline chord or line-based methods, weighted infarct transmurality based methods, spatial maximal transmurality based methods and/or a combination thereof.
  • Infarct may be first delineated using any of the image segmentation methods described herein.
  • infarct transmurality can be then measured using visual assessment based 5-point scale scoring for defining transmurality as 0%, 1-25%, 25- 50%, 50-75%) and 75-100%), as described in, for example, Schulz-Menger J, et al. Standardized image interpretation and post processing in cardiovascular magnetic resonance: Society for Cardiovascular Magnetic Resonance (SCMR) board of trustees task force on standardized post processing.
  • SCMR Society for Cardiovascular Magnetic Resonance
  • infarct transmurality can be measured by measuring the extent of infarct across any number of concentric segments defined along the transmural extent of the myocardium as described in, for example Perin EC, et al. Assessing myocardial viability and infarct transmurality with left ventricular electromechanical mapping in patients with stable coronary artery disease: validation by delayed-enhancement magnetic resonance imaging. Circulation. 2002; 106(8):957-61.
  • infarct transmurality can be measured using area-based quantification, radial extent-based quantification, weighted-infarct transmurality and/or spatial maximal scar transmurality, as described in, for example, Alexandre J, et al. Scar extent evaluated by late gadolinium enhancement CMR: a powerful predictor of long term appropriate ICD therapy in patients with coronary artery disease. J Cardiovasc Magn Reson. 2013; 15: 12.
  • the Tl -weighted images are obtained at a magnetic field strength of any one or more of 3.0 Tesla, about 3.0 to about 4.0 Tesla, about 4.0 to about 5.0 Tesla, about 5.0 to about 6.0 Tesla, about 6.0 to about 7.0 Tesla, about 7.0 to about 8.0 Tesla, about 8.0 to about 9.0 Tesla, about 9.0 to about 10.0 Tesla, about 10.0 to about 11.0 Tesla, about 11.0 to about 12.0 Tesla, about 12.0 to about 13.0 Tesla, about 13.0 to about 14.0 Tesla, 14.0 to about 15.0 Tesla, 15.0 to about 16.0 Tesla, about 16.0 to about 17.0 Tesla, about 17.0 to about 18.0 Tesla, about 18.0 to about 19.0 Tesla, about 19.0 to about 20.0 Tesla, about 20.0 to about 21.0 Tesla, about 21.0 to about 22.0 Tesla or a combination thereof.
  • Cardiac MRI allows for the assessment of cardiac function and characterization of myocardial tissue.
  • cardiac MRI performed by the methods described herein, permits noninvasive determination of the location and quantification of myocardial infarct size and transmurality without the need for exogenous contrast agents.
  • the accuracy of the method described herein, for characterizing the myocardium post-infarction at field strength of about 3.0 Tesla without using exogenous contrast media is about the same as the images obtained using currently established methods that include the use of a contrast agent such as gadolinium.
  • the methods described herein are useful for subjects who are contra-indicated for exogenous contrast agents (for example, subjects with renal insufficiency) but need a cardiac MRI for diagnostic purposes.
  • the proposed method enables faster cardiac MRI exams given that there is no need to wait to establish differential kinetics of contrast media through the healthy and infarcted myocardium; specifically, current methods include that the subjects wait in the MR scanner for about 10 minutes after the contrast agent is administered whereas the methods described herein eliminate this dead time. Further, without the use of contrast agent, if an error is made during image acquisition, a scan may be repeated to obtain new images.
  • the proposed scheme also overcomes the expenses associated with contrast-based approaches for characterizing myocardial infarctions. Unlike the qualitative nature of LGE images, the proposed technique is quantitative and thereby allows serial evaluation of myocardial infarction healing and remodeling. Since the technique does not require an exogenous contrast agent, the technique is not limited by gadolinium wash-in and wash-out kinetics. The technique also does not impose specific absorption rate limitations that are commonly encountered with other techniques such as Tip imaging.
  • Late gadolinium enhanced (LGE) CMR is a powerful tool for characterizing myocardial infarctions. Nevertheless, the need for gadolinium infusion for LGE imaging poses limitations in certain patient populations and imaging workflow. Through controlled studies in canines, this work explores the capability of Tl imaging at 3T as an alternative to LGE for characterizing chronic MI without exogenous contrast media.
  • CMR Cardiovascular Magnetic Resonance
  • Non-contrast Tl and LGE images were acquired and used to identify infarct location, size and transmurality.
  • T2 maps were acquired and analyzed for differences between acute and chronic infarctions.
  • Ex-vivo triphenyl tetrazolium chloride and Elastin Masson's Trichrome stainings showed extensive replacement fibrosis within the infarcted territories in the chronic phase.
  • Sensitivity and specificity of non-contrast Tl maps at 3T were 94% and 94% respectively for detecting acute myocardial infarctions, and 95% and 97% respectively for detecting chronic myocardial infarctions.
  • Non-contrast Tl maps at 3T can be used to determine the location, size and transmurality of chronic myocardial infarctions with high diagnostic accuracy. Patient studies are necessary for clinical translation.
  • the left anterior descending (LAD) artery was isolated and ligated at a point immediately distal to the first branch. Reperfusion was established by removing the ligation 3 hours after the onset of ischemia. The chest was closed and the animal was allowed to recover for 7 days before the Cardiac Magnetic Resonance (CMR) studies. Cardiac Magnetic Resonance Studies
  • ECG-triggered breath-held cine-SSFP pre- contrast Tl -weighted and pre-contrast T2-weighted images of contiguous slices covering the entire LV were acquired along the short-axis and long-axis views at both 3T and 1.5T. All imaging studies were completed with the acquisition of Late Gadolinium Enhancement (LGE) images 8-10 minutes following intravenous administration of 0.2 mmol/kg body wt. gadopentate dimeglumine (Magnevist, Bayer Healthcare Pharmaceuticals Inc., Wayne, NJ). Imaging sequences and measurement parameters used to acquire different images are summarized in Table 1. To minimize surface coil bias, pre-scan normalization was applied for each scan.
  • LGE Late Gadolinium Enhancement
  • Table 1 Typical imaging parameters used to acquire different CMR images at 1.5T and 3T
  • Tl and T2 maps were constructed from the pre-contrast Tl -weighted and T2- weighted images respectively. All image analyses were performed on cvi42 image analysis software (Circle Cardiovascular Imaging Inc., Calgary, Canada). Endocardial and epicardial contours were carefully drawn to delineate the left- ventricular (LV) myocardium from the LV blood pool and pericardium. Remote (viable) myocardium was identified on LGE images as the region showing no hyperintensity. A reference ROI was drawn in the remote myocardium. Infarcted myocardium was then indentified on the LGE image as the region with mean signal intensity >5 standard deviations (SDs) than that of reference ROI.
  • SDs standard deviations
  • Hypointense cores of microvascular obstruction that were not detected as infarcted myocardium on LGE images by the thresholding criteria were manually included in the final analysis for infarct size and transmurality.
  • the reference ROI drawn on LGE image was copied on to the corresponding Tl map.
  • Infarcted myocardium was then identified on the Tl map using the same Mean + 5 SDs criterion.
  • Hypointense cores of acute hemorrhage or chronic iron deposition that were not detected as infarcted myocardium on Tl maps were manually included in the final analysis for infarct size and transmurality. Tl values of the remote myocardium and infarcted myocardium (excluding the hypointense core) were measured.
  • Infarct sizes from both LGE images and Tl maps were measured as the percentage of total left-ventricular (LV) volume and compared.
  • percentage infarct size was also measured on a segmental basis using the standard American Heart Association (AHA) 17-segment model 41 . Measurements from the 17 th segment were excluded from the final analysis to discount the partial voluming effects at the LV apex.
  • AHA American Heart Association
  • each myocardial slice was divided into 100 equally spaced chords between the endocardial and epicardial contours with the first chord starting at the anterior insertion of right ventricle (RV) into the left ventricle (LV).
  • RV right ventricle
  • LV left ventricle
  • Mean transmurality for the entire infarct was obtained by averaging the infarct transmurality of all the chords across all the slices that have at least 1% scar extent 42 .
  • Bulls-eye plots depicting the extent (using AHA 17-segment model) and transmurality (using chord-based division of each myocardial slice) were also obtained for both LGE images and Tl maps.
  • ROIs were drawn in infarcted and remote myocardium identified on the corresponding LGE images using the Mean+5SD criterion. These ROIs were then copied on to both Tl maps and T2 maps to measure and compare the Tl and T2 values of the infarcted and remote myocardium. Tl and T2 values of the hypointense cores within infarcted territories were excluded from the analysis to eliminate the counteracting effects of acute hemorrhage or chronic iron deposition on acute myocardial edema or chronic replacement fibrosis. Percentage change in the LGE signal intensity and Tl values of infarcted myocardium was measured with respect to the remote myocardium.
  • Representative LGE images and Tl maps acquired at 7 days post reperfusion from a canine scanned at 3T are shown in Figure 1.
  • Bulls-eye plots depicting the extent and transmurality of infarcted myocardium are also shown for both LGE images and Tl maps in Figure 1.
  • Location and spatial extent of the infarct were closely correlated between LGE images and Tl maps.
  • mean infarct size measured on Tl maps was modestly higher than that measured on LGE images (13.3 ⁇ 8.4% vs.
  • LGE images and Tl maps acquired from a canine scanned at 3T at 4 months post reperfusion are shown in Figure 3.
  • Bulls-eye plots depicting the extent and transmurality of infarcted myocardium are also shown for LGE images and Tl maps in Figure 3.
  • Table 2 summarizes the Tl, T2 and LGE signal intensity characteristics of infarcted and remote myocardium at 3T and 1.5T during acute and chronic phases post reperfusion. Representative LGE images, Tl maps and T2 maps acquired from four different canines at 3T and 1.5T during acute and chronic phases of infarction are shown in Figure 9.
  • Table 2 Tl, T2 and LGE signal intensity characteristics of acute and chronic myocardial infarction at 1.5T and 3T
  • Mean Tl of the infarcted myocardium at 1.5T during the acute phase of infarction was 184 ⁇ 77ms higher than that of remote myocardium (p ⁇ 0.001), while mean T2 of the infarcted myocardium was 20 ⁇ 7ms higher than that of remote myocardium (p ⁇ 0.001). Percentage change in the signal intensity of infarcted myocardium relative to remote myocardium was nearly 26-fold higher in LGE images compared to the Tl maps at 1.5T (p ⁇ 0.001). Compared to 1.5T, infarcted myocardium to remote myocardium Tl contrast during the acute phase of infarction was nearly 2-fold higher at 3T.
  • Figure 10 shows representative LGE images and Tl maps acquired at 3T from three different canines at 4 months post reperfusion along with slice-matched ex-vivo TTC and EMT staining images.
  • the spatial extent and location of myocardial infarction correlated well among LGE images, Tl maps and ex-vivo TTC images.
  • EMT staining showed extensive replacement fibrosis within the infarcted myocardium which validated that Tl hyperintensity in the chronic phase of infarction predominantly arose of fibrosis. Similar observations were made in the other animals.
  • non-contrast Tl mapping holds a great potential for widespread clinical applicability in the setting of acute and chronic myocardial infarctions. While a few studies assessed the prognostic significance of Tl hyperenhancement in acute myocardial infarctions, future studies that elucidate the relationship of Tl hyperenhancement in the chronic phases of infarction to long-term LV function, collagen metabolism and extracellular matrix remodeling are warranted. In particular, the ability of non-contrast Tl mapping to detect and characterize microvascular obstruction and acute reperfusion hemorrhage - two important biomarkers with significant implications for long-term patient prognosis - need to be closely studied.
  • non-contrast Tl mapping can potentially provide a tool for comprehensive tissue characterization.
  • Non-contrast Tl mapping at 3T can reliably determine infarct location, size, and transmurality in chronic myocardial infarctions with very high diagnostic accuracy that is comparable to conventional LGE imaging. Given its quantitative nature and non-reliance on exogenous contrast media, this technique presents a potential alternative for viability imaging where LGE imaging is contraindicated.
  • an inversion-recovery preparation that nulls the remote myocardium gives a 12% equilibrium magnetization available for readout from the infarcted territories.
  • the contrast- enhanced Tl values (10 minutes post-gadolinium injection) of remote and infarcted myocardium at 3T are 400ms and 150ms respectively
  • an inversion-recovery sequence that nulls the remote myocardium gives a 67% equilibrium magnetization available for readout from the infarcted territories.
  • inversion-recovery preparation can improve the image contrast between infarcted and remote territories by 500%. While this is expected to improve the visualization of chronic infarctions, the current Tl mapping approach evaluated here still provides excellent diagnostic accuracy.
  • the inventors develop and test a time efficient, high resolution, free-breathing 3D bSSFP contrast-agent free CMR method with optimal Ti- and MT-weighting for improved visualization of chronic MI regions at 3T. Based on our findings, our proposed approach has the capacity to overcome some of the key limitations of LGE CMR.
  • MOLLI modified look- locker inversion recovery
  • K-space data, time stamped for trigger time (via ECG gating) will be acquired over mid diastole using a stack-of-stars IR-prepared bSSFP pulse sequence (spatial resolution: 1.5x1.5x1.5 mm 3 , nominal in-plane FOV: 290x290, in-plane matrix size: 192x192) with optimized TI time (Step 2).
  • a stack-of-stars IR-prepared bSSFP pulse sequence spatial resolution: 1.5x1.5x1.5 mm 3 , nominal in-plane FOV: 290x290, in-plane matrix size: 192x192
  • Central k-space lines corresponding to each cardiac phase will be used to derive the center of mass (COM) curves along the z-axis via 1-D fast Fourier transform (FFT).
  • FFT 1-D fast Fourier transform
  • the k-space lines will be sorted into 6 bins, each corresponding to a respiratory state with the first bin as the reference bin (end-expiration) and the last bin as bin 6 (end inspiration).
  • the data will be processed with a 3D Gaussian filter, followed by re-gridding the radial lines, application of a spatial mask (to restrict the registration to region of the heart) and performing FFT to obtain the under sampled 3D image for each respiratory bin.
  • the k-space data will again be divided into 6-respiratory bins, re-gridded, transformed to the reference image (3D affine transform), summed together, and the final 3D image will be reconstructed.
  • the inventors examine and compare different thresholding criteria and visual delineation for detecting chronic myocardial infarctions (Mis) on native Tl maps at 3.0T.
  • Native Tl maps and Late Gadolinium Enhancement (LGE) images were acquired at 3.0T at 4 months following MI. MI detected on LGE images using Mean + 5 Standard Deviations (SDs) criterion was considered to be the gold standard.
  • Mean+2SD, Mean+3SD, Mean+4SD, Mean+5SD, Mean+6SD, Otsu's, and visual delineation techniques were used to detect MI on Tl maps. Infarct size and transmurality measured from native Tl maps using these techniques were compared to those measured from LGE images, and their diagnostic performance was evaluated.
  • Threshold-based detection using Mean+5SD criterion can reliably determine the size, location and transmurality of chronic Mis from native Tl maps at 3.0T.

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Abstract

L'invention concerne des procédés de caractérisation d'un infarctus du myocarde au moyen de l'imagerie par résonance magnétique, sans utiliser d'agents de contraste, en utilisant, par exemple, une intensité de champ de supérieure ou égale à 3,0 Tesla. L'invention concerne également un procédé de détection d'un infarctus du myocarde chronique chez un sujet chez lequel on suspecte un infarctus du myocarde.
PCT/US2014/053938 2013-09-03 2014-09-03 Viabilité myocardique par irm sans milieu de contraste exogène WO2015034951A1 (fr)

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WO2017040538A1 (fr) * 2015-08-31 2017-03-09 The Board Of Trustees Of The Leland Stanford Junior University Imagerie par résonance magnétique à haute résolution et acquisition comprimée

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US20070014452A1 (en) * 2003-12-01 2007-01-18 Mitta Suresh Method and system for image processing and assessment of a state of a heart
US20080108894A1 (en) * 2004-11-15 2008-05-08 Elgavish Gabriel A Methods and Systems of Analyzing Clinical Parameters and Methods of Producing Visual Images
US20120019245A1 (en) * 2010-07-20 2012-01-26 The Trustees Of The University Of Pennsylvania Cest mri methods for imaging of metabolites and the use of same as biomarkers
WO2012174157A1 (fr) * 2011-06-13 2012-12-20 Cedars-Sinai Medical Center Évaluation de dépôt de fer après un infarctus du myocarde, en tant que marqueur d'une hémorragie du myocarde

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US20070014452A1 (en) * 2003-12-01 2007-01-18 Mitta Suresh Method and system for image processing and assessment of a state of a heart
US20080108894A1 (en) * 2004-11-15 2008-05-08 Elgavish Gabriel A Methods and Systems of Analyzing Clinical Parameters and Methods of Producing Visual Images
US20120019245A1 (en) * 2010-07-20 2012-01-26 The Trustees Of The University Of Pennsylvania Cest mri methods for imaging of metabolites and the use of same as biomarkers
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WO2017040538A1 (fr) * 2015-08-31 2017-03-09 The Board Of Trustees Of The Leland Stanford Junior University Imagerie par résonance magnétique à haute résolution et acquisition comprimée
KR20180048808A (ko) * 2015-08-31 2018-05-10 더 보드 오브 트러스티스 오브 더 리랜드 스탠포드 쥬니어 유니버시티 압축 센싱 고해상도 기능 자기 공명 영상법
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