Magnetic Resonance Diffusion Tensor Imaging Provides New Insights Into the Microstructural Alterations in Dilated Cardiomyopathy
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Abstract
HomeCirculation: Cardiovascular ImagingVol. 9, No. 10Magnetic Resonance Diffusion Tensor Imaging Provides New Insights Into the Microstructural Alterations in Dilated Cardiomyopathy Free AccessEditorialPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessEditorialPDF/EPUBMagnetic Resonance Diffusion Tensor Imaging Provides New Insights Into the Microstructural Alterations in Dilated Cardiomyopathy Christopher T. Nguyen, PhD, Gerald Buckberg, MD and Debiao Li, PhD Christopher T. NguyenChristopher T. Nguyen From the Department of Biomedical Sciences, Biomedical Imaging Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA (C.T.N., D.L.); Departments of Cardiac Surgery (G.B.) and Medicine (D.L.), David Geffen School of Medicine at University of California, Los Angeles; and Department of Bioengineering, University of California, Los Angeles (D.L.). , Gerald BuckbergGerald Buckberg From the Department of Biomedical Sciences, Biomedical Imaging Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA (C.T.N., D.L.); Departments of Cardiac Surgery (G.B.) and Medicine (D.L.), David Geffen School of Medicine at University of California, Los Angeles; and Department of Bioengineering, University of California, Los Angeles (D.L.). and Debiao LiDebiao Li From the Department of Biomedical Sciences, Biomedical Imaging Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA (C.T.N., D.L.); Departments of Cardiac Surgery (G.B.) and Medicine (D.L.), David Geffen School of Medicine at University of California, Los Angeles; and Department of Bioengineering, University of California, Los Angeles (D.L.). Originally published11 Oct 2016https://doi.org/10.1161/CIRCIMAGING.116.005593Circulation: Cardiovascular Imaging. 2016;9:e005593Cardiac magnetic resonance (CMR) diffusion tensor imaging (DTI) is a promising technique capable of probing the myocardial microstructure by assessing the myofiber orientation.1,2 New technical developments in CMR DTI in recent years3–8 have allowed the clinical application of this powerful imaging technique. CMR DTI has been used to study myocardial infarction9,10 and hypertrophic cardiomyopathy11,12 in patients, revealing their adverse effects on myocardial microstructure. The article in this issue of Circulation: Cardiovascular Imaging by von Deuster et al13 describes a new clinical application of CMR DTI.See Article by von Deuster et alIn this single-center study, von Deuster et al13 studied patients with dilated cardiomyopathy (DCM) using CMR DTI and assessed the change in the myocardial fiber orientation by imaging at 2 separate time points in the cardiac cycle. DCM is a major cause of heart failure that causes ventricular chamber enlargement, wall thinning, and systolic dysfunction. The authors hypothesized that a combination of CMR DTI, myocardial tagging, and biomechanical modeling will shed new insight into the alterations of myocardial microstructure and functional performance (strain) in patients with DCM when compared with healthy controls. They measured helix angle transmurality (HAT) and found it was steeper in patients DCM when compared with age-matched controls. Conversely, it was impaired during cardiac contraction in patients with DCM, compared with controls. Their developed biomechanical modeling could not explain the steeper HAT in patients with DCM, but could support the impaired dynamic reorientation of fibers.This study displays the superb and important teamwork between clinicians and scientists that allows this cutting-edge imaging technology into clinical evaluation of cardiovascular diseases, such as DCM. Their biomechanical modeling did not support the steeper helix angulation, but it is a natural extension to collect functional and microstructural CMR data. In addition, the recruitment and scanning of patients with DCM are a major accomplishment, as many DCM patients may have implantable MR incompatible hardware such as ICD, LVAD, or pacemakers.Although we greatly appreciate the enormous technical challenges that were overcome in completing the study, the choice of CMR DTI technique raises concerns about its accuracy in patients with DCM. For example, the dual-phase stimulated echo (STEAM) diffusion CMR technique14 requires breath-holds to achieve a clinically acceptable scan time since prospective navigator gating has low scan time efficiency.4 Consequently, each patient underwent 22 breath-holds to achieve the necessary siganl-to-noise ratio to robustly map myocardial fiber orientations at a single short-axis slice. This is in comparison with the typical 16 to 20 breath-holds needed for full LV coverage of functional and late gadolinium enhancement imaging in a routine clinical CMR examination. Furthermore, the STEAM technique is susceptible to arrhythmia when scanning outside of systole because STEAM diffusion encoding is achieved over 2 heart beats.Therefore, STEAM DTI requires neighboring heartbeats to be encoded in the exact same position to avoid irreversible motion-induced signal loss. Alternative techniques to address patient comfort and arrhythmia would be motion compensated spin echo diffusion CMR techniques3,5,7,8 that diffusion encode in a single heart beat allowing for free breathing and more robustness to arrhythmia. Future improvements to the STEAM DTI CMR technique are needed to reduce the burden of patients.Another technical concern is the estimation of HAT, defined as the slope of the transmural helix angle course, in patients with DCM. Patients with DCM exhibit thinning of the left ventriclular wall,15,16 making it challenging for diffusion CMR to accurately quantify the HAT with the spatial resolution (2.5×2.5×8 mm3) used in the study. The reported wall thickness for patients with DCM used in the study was 9±1 mm, and only the inner 80% of the wall was used to calculate the HAT yielding a total of 2 to 3 pixels at each radial spoke. Further studies are needed to validate if 2 to 3 pixels is sufficient to yield an accurate estimate of HAT.A final and perhaps the most vital consideration is their conclusion that there is a steeper diastolic helix angulation in patients with DCM than in normal subjects. This finding is not only inconsistent with the biomechanical model used in the study (Figure 7) but, most importantly, it is inconsistent in studies of ex vivo human hearts,17,18 where there is a flattening of the helix angulation. Their own strain data support this, as the longitudinal strain is reduced. This diminution of shortening during torsion occurs because the fibers have a more horizontal orientation, as described by Sallin.19 We wonder how this fundamental difference between structure and function can be resolved because the steeper helical angulation would enhance, rather than diminish cardiac performance. We look forward to their further studies to provide clarification.In summary, we commend the authors for adding to the ever growing clinical use of diffusion CMR. Interfacing myocardial microstructure and its dynamics offers a new exciting perspective to our knowledge and may extend far beyond studying DCM. Technically, CMR DTI will need to be further improved to reduce the burden of patients. The future holds great promise for using CMR DTI to accurately quantify HAT. A concert of experimental studies is needed in order for this potential to be explored and further validated. We believe that CMR DTI will become a powerful tool to facilitate our understanding of the relationship between myocardial structure and functional performance of the heart and potentially improve diagnosis and treatment of cardiovascular disease.DisclosuresNone.FootnotesThe opinions expressed in this article are not necessarily those of the editors or of the American Heart Association.Correspondence to Debiao Li, PhD, Biomedical Imaging Research Institute, Cedars-Sinai Medical Center, Pacific Theatres (PACT), Suite 800, 8700 Beverly Blvd, Los Angeles, CA 90048. E-mail [email protected]References1. Mekkaoui C, Reese TG, Jackowski MP, Bhat H, Sosnovik DE. Diffusion MRI in the heart.NMR Biomed. 2015; doi: 10.1002/nbm.3426MedlineGoogle Scholar2. Froeling M, Strijkers GJ, Nederveen AJ, Chamuleau SA, Luijten PR. Diffusion tensor MRI of the heart – in vivo imaging of myocardial fiber architecture.Curr Cardiovasc Imaging Rep. 2014; 7:9276.CrossrefGoogle Scholar3. Nguyen C, Fan Z, Sharif B, He Y, Dharmakumar R, Berman DS, Li D. In vivo three-dimensional high resolution cardiac diffusion-weighted MRI: a motion compensated diffusion-prepared balanced steady-state free precession approach.Magn Reson Med. 2014; 72:1257–1267. doi: 10.1002/mrm.25038.CrossrefMedlineGoogle Scholar4. Nielles-Vallespin S, Mekkaoui C, Gatehouse P, Reese TG, Keegan J, Ferreira PF, Collins S, Speier P, Feiweier T, de Silva R, Jackowski MP, Pennell DJ, Sosnovik DE, Firmin D. In vivo diffusion tensor MRI of the human heart: reproducibility of breath-hold and navigator-based approaches.Magn Reson Med. 2013; 70:454–465. doi: 10.1002/mrm.24488.CrossrefMedlineGoogle Scholar5. Stoeck CT, von Deuster C, Genet M, Atkinson D, Kozerke S. Second-order motion-compensated spin echo diffusion tensor imaging of the human heart.Magn Reson Med. 2016; 75:1669–1676. doi: 10.1002/mrm.25784.CrossrefMedlineGoogle Scholar6. Moulin K, Croisille P, Feiweier T, Delattre BM, Wei H, Robert B, Beuf O, Viallon M. In vivo free-breathing DTI and IVIM of the whole human heart using a real-time slice-followed SE-EPI navigator-based sequence: a reproducibility study in healthy volunteers.Magn Reson Med. 2016; 76:70–82. doi: 10.1002/mrm.25852.CrossrefMedlineGoogle Scholar7. Aliotta E, Wu HH, Ennis DB. Convex optimized diffusion encoding (CODE) gradient waveforms for minimum echo time and bulk motion-compensated diffusion-weighted MRI.Magn Reson Med. 2016; doi: 10.1002/mrm.26166.MedlineGoogle Scholar8. Nguyen C, Fan Z, Xie Y, Pang J, Speier P, Bi X, Kobashigawa J, Li D. In vivo diffusion tensor MRI of the human heart on a 3 tesla clinical scanner: an optimized second order (M2) motion compensated diffusion-preparation approach [published online ahead of print August 23, 2016].Magn Reson Med. 2016; doi: 10.1002/mrm.26380.CrossrefGoogle Scholar9. Wu MT, Tseng WY, Su MY, Liu CP, Chiou KR, Wedeen VJ, Reese TG, Yang CF. Diffusion tensor magnetic resonance imaging mapping the fiber architecture remodeling in human myocardium after infarction: correlation with viability and wall motion.Circulation. 2006; 114:1036–1045. doi: 10.1161/CIRCULATIONAHA.105.545863.LinkGoogle Scholar10. Wu MT, Su MY, Huang YL, Chiou KR, Yang P, Pan HB, Reese TG, Wedeen VJ, Tseng WY. Sequential changes of myocardial microstructure in patients postmyocardial infarction by diffusion-tensor cardiac MR: correlation with left ventricular structure and function.Circ Cardiovasc Imaging. 2009; 2:32–40. doi: 10.1161/CIRCIMAGING.108.778902.LinkGoogle Scholar11. Nguyen C, Lu M, Fan Z, Bi X, Kellman P, Zhao S, Li D. Contrast-free detection of myocardial fibrosis in hypertrophic cardiomyopathy patients with diffusion-weighted cardiovascular magnetic resonance.J Cardiovasc Magn Reson. 2015; 17:107. doi: 10.1186/s12968-015-0214-1.CrossrefMedlineGoogle Scholar12. Ferreira PF, Kilner PJ, McGill LA, Nielles-Vallespin S, Scott AD, Ho SY, McCarthy KP, Haba MM, Ismail TF, Gatehouse PD, de Silva R, Lyon AR, Prasad SK, Firmin DN, Pennell DJ. In vivo cardiovascular magnetic resonance diffusion tensor imaging shows evidence of abnormal myocardial laminar orientations and mobility in hypertrophic cardiomyopathy.J Cardiovasc Magn Reson. 2014; 16:87. doi: 10.1186/s12968-014-0087-8.CrossrefMedlineGoogle Scholar13. Von Deuster C, Sammut E, Asner L, Nordsletten D, Lamata P, Stoeck CT, Kozerke S, Razavi R. Studying dynamic myofiber aggregate reorientation in dilated cardiomyopathy using in-vivo magnetic resonance diffusion tensor imaging.Circ Cardiovasc Imaging. 2016; 9:e005018. doi: 10.1161/CIRCIMAGING.116.005018.LinkGoogle Scholar14. Stoeck CT, Kalinowska A, von Deuster C, Harmer J, Chan RW, Niemann M, Manka R, Atkinson D, Sosnovik DE, Mekkaoui C, Kozerke S. Dual-phase cardiac diffusion tensor imaging with strain correction.PLoS One. 2014; 9:e107159. doi: 10.1371/journal.pone.0107159.CrossrefMedlineGoogle Scholar15. Luk A, Ahn E, Soor GS, Butany J. Dilated cardiomyopathy: a review.J Clin Pathol. 2009; 62:219–225. doi: 10.1136/jcp.2008.060731.CrossrefMedlineGoogle Scholar16. Japp AG, Gulati A, Cook SA, Cowie MR, Prasad SK. The Diagnosis and Evaluation of Dilated Cardiomyopathy.J Am Coll Cardiol. 2016; 67:2996–3010. doi: 10.1016/j.jacc.2016.03.590.CrossrefMedlineGoogle Scholar17. MacGowan GA, Shapiro EP, Azhari H, Siu CO, Hees PS, Hutchins GM, Weiss JL, Rademakers FE. Noninvasive measurement of shortening in the fiber and cross-fiber directions in the normal human left ventricle and in idiopathic dilated cardiomyopathy.Circulation. 1997; 96:535–541.LinkGoogle Scholar18. Buckberg GD, Coghlan HC, Torrent-Guasp F. The structure and function of the helical heart and its buttress wrapping. V. Anatomic and physiologic considerations in the healthy and failing heart.Semin Thorac Cardiovasc Surg. 2001; 13:358–385.CrossrefMedlineGoogle Scholar19. Sallin EA. Fiber orientation and ejection fraction in the human left ventricle.Biophys J. 1969; 9:954–964. doi: 10.1016/S0006-3495(69)86429-5.CrossrefMedlineGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetailsCited By Pop M and Stefu N (2020) Diffusion Magnetic Resonance Imaging with Applications to Cardiac Muscle: Short Review, Annals of West University of Timisoara - Physics, 10.2478/awutp-2020-0007, 62:1, (108-119), Online publication date: 1-Dec-2020., Online publication date: 1-Dec-2020. Čelutkienė J, Plymen C, Flachskampf F, de Boer R, Grapsa J, Manka R, Anderson L, Garbi M, Barberis V, Filardi P, Gargiulo P, Zamorano J, Lainscak M, Seferovic P, Ruschitzka F, Rosano G and Nihoyannopoulos P (2018) Innovative imaging methods in heart failure: a shifting paradigm in cardiac assessment. Position statement on behalf of the Heart Failure Association of the European Society of Cardiology, European Journal of Heart Failure, 10.1002/ejhf.1330, 20:12, (1615-1633), Online publication date: 1-Dec-2018. October 2016Vol 9, Issue 10 Advertisement Article InformationMetrics © 2016 American Heart Association, Inc.https://doi.org/10.1161/CIRCIMAGING.116.005593PMID: 27729369 Originally publishedOctober 11, 2016 KeywordsEditorialshumandiffusion tensor imagingdilated cardiomyopathysystoleheart failurePDF download Advertisement SubjectsCardiomyopathyHeart FailureMagnetic Resonance Imaging (MRI)Remodeling
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Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.002 | 0.003 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.002 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
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How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".