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      In vivo cardiovascular magnetic resonance diffusion tensor imaging shows evidence of abnormal myocardial laminar orientations and mobility in hypertrophic cardiomyopathy

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          Abstract

          Background

          Cardiac diffusion tensor imaging (cDTI) measures the magnitudes and directions of intramyocardial water diffusion. Assuming the cross-myocyte components to be constrained by the laminar microstructures of myocardium, we hypothesized that cDTI at two cardiac phases might identify any abnormalities of laminar orientation and mobility in hypertrophic cardiomyopathy (HCM).

          Methods

          We performed cDTI in vivo at 3 Tesla at end-systole and late diastole in 11 healthy controls and 11 patients with HCM, as well as late gadolinium enhancement (LGE) for detection of regional fibrosis.

          Results

          Voxel-wise analysis of diffusion tensors relative to left ventricular coordinates showed expected transmural changes of myocardial helix-angle, with no significant differences between phases or between HCM and control groups. In controls, the angle of the second eigenvector of diffusion (E2A) relative to the local wall tangent plane was larger in systole than diastole, in accord with previously reported changes of laminar orientation. HCM hearts showed higher than normal global E2A in systole (63.9° vs 56.4° controls, p = 0.026) and markedly raised E2A in diastole (46.8° vs 24.0° controls, p < 0.001). In hypertrophic regions, E2A retained a high, systole-like angulation even in diastole, independent of LGE, while regions of normal wall thickness did not (LGE present 57.8°, p = 0.0028, LGE absent 54.8°, p = 0.0022 vs normal thickness 38.1°).

          Conclusions

          In healthy controls, the angles of cross-myocyte components of diffusion were consistent with previously reported transmural orientations of laminar microstructures and their changes with contraction. In HCM, especially in hypertrophic regions, they were consistent with hypercontraction in systole and failure of relaxation in diastole. Further investigation of this finding is required as previously postulated effects of strain might be a confounding factor.

          Electronic supplementary material

          The online version of this article (doi:10.1186/s12968-014-0087-8) contains supplementary material, which is available to authorized users.

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          Most cited references32

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          Inferring microstructural features and the physiological state of tissues from diffusion-weighted images.

          P Basser (1995)
          We review several methods that have been developed to infer microstructural and physiological information about isotropic and anisotropic tissues from diffusion weighted images (DWIs). These include Diffusion Imaging (DI), Diffusion Tensor Imaging (DTI), isotropically weighted imaging, and q-space imaging. Just as DI provides useful information about molecular displacements in one dimension with which to characterize diffusion in isotropic tissues, DTI provides information about molecular displacements in three dimensions needed to characterize diffusion is anisotropic tissues. DTI also furnishes scalar parameters that behave like quantitative histological or physiological 'stains' for different features of diffusion. These include Trace(D), which is related to the mean diffusivity, and a family of parameters derived from the diffusion tensor, D, which characterize different features of anisotropic diffusion. Simple thought experiments and geometrical constructs, such as the diffusion ellipsoid, can be used to understand water diffusion in isotropic and anisotropic media, and the NMR experiments used to characterize it.
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            Coronary microvascular dysfunction and prognosis in hypertrophic cardiomyopathy.

            Microvascular dysfunction, reflected by an inadequate increase in myocardial blood flow in response to dipyridamole infusion, is a recognized feature of hypertrophic cardiomyopathy. Its long-term effect on the prognosis is unknown. We prospectively evaluated a cohort of patients with hypertrophic cardiomyopathy after they had undergone quantitative assessment of myocardial blood flow by positron-emission tomography (PET). Fifty-one patients (New York Heart Association class I or II) were followed for a mean (+/-SD) of 8.1+/-2.1 years after PET. Twelve subjects with atypical chest pain served as controls. Measurement of flow was performed at base line and after the infusion of the coronary vasodilator dipyridamole, with the use of nitrogen-13-labeled ammonia. Patients were then divided into three equal groups with increasing values of myocardial blood flow. The response of myocardial blood flow to dipyridamole was severely blunted in the patients, as compared with the controls (1.50+/-0.69 vs. 2.71+/-0.94 ml per minute per gram of tissue, P<0.001). Sixteen patients (31 percent) had an unfavorable outcome (death from cardiovascular causes, progression to New York Heart Association class III or IV, or sustained ventricular arrhythmias requiring the implantation of a cardioverter-defibrillator) 2.2 to 9.1 years after PET. Reduced blood flow in response to dipyridamole was strongly associated with an unfavorable outcome. Multivariate analysis showed that among patients in the lowest of the three flow groups the age-adjusted relative hazard of death from cardiovascular causes was 9.6 (P=0.02) and the relative hazard of an unfavorable outcome (a combined end point) was 20.1 (P=0.003), as compared with patients in the two other flow groups. Specifically, all four patients who died from heart failure and three of five who died suddenly were in this subgroup. In patients with hypertrophic cardiomyopathy, the degree of microvascular dysfunction is a strong, independent predictor of clinical deterioration and death. Severe microvascular dysfunction is often present in patients with mild or no symptoms and may precede clinical deterioration by years. Copyright 2003 Massachusetts Medical Society
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              Histological validation of myocardial microstructure obtained from diffusion tensor magnetic resonance imaging.

              Diffusion tensor magnetic resonance imaging (MRI) is a possible new means of elucidating the anatomic structure of the myocardium. It enjoys several advantages over traditional histological approaches, including the ability to rapidly measure fiber organization in isolated, perfused, arrested hearts, thereby avoiding fixation and sectioning of artifacts. However, quantitative validation of this MRI method has been lacking. Here, fiber orientations estimated in the same locations in the same heart using both diffusion tensor MRI and histology are compared in a total of two perfused rabbit hearts. Fiber orientations were statistically similar for both methods and differed on average by 12 degrees at any single location. This is similar to the 10 degrees uncertainty in fiber orientation achieved with histology. In addition, imaging studies performed in a total of seven hearts support a level of organization beyond the myofiber, the recently described laminar organization of the ventricular myocardium.
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                Author and article information

                Contributors
                p.ferreira@rbht.nhs.uk
                p.kilner@rbht.nhs.uk
                l.mcGill@rbht.nhs.uk
                sonia.nielles-vallespin@nih.gov
                a.scott@rbht.nhs.uk
                yen.ho@rbht.nhs.uk
                k.mccarthy@rbht.nhs.uk
                margarita_murillo@unex.es
                t.ismail@rbht.nhs.uk
                p.gatehouse@rbht.nhs.uk
                r.desilva@imperial.ac.uk
                a.lyon@imperial.ac.uk
                s.prasad@rbht.nhs.uk
                d.firmin@ic.ac.uk
                dj.pennell@rbht.nhs.uk
                Journal
                J Cardiovasc Magn Reson
                J Cardiovasc Magn Reson
                Journal of Cardiovascular Magnetic Resonance
                BioMed Central (London )
                1097-6647
                1532-429X
                12 November 2014
                12 November 2014
                2014
                : 16
                : 1
                : 87
                Affiliations
                [ ]National Institute of Health Research Cardiovascular Biomedical Research Unit, Royal Brompton Hospital and Imperial College, London, UK
                [ ]National Institutes of Health, Bethesda, USA
                Article
                87
                10.1186/s12968-014-0087-8
                4229618
                25388867
                8a2c5d4d-7c13-4487-ad19-c4ea9b4e5b2e
                © Ferreira et al.; licensee BioMed Central Ltd. 2014

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 3 March 2014
                : 24 September 2014
                Categories
                Research
                Custom metadata
                © The Author(s) 2014

                Cardiovascular Medicine
                diffusion tensor imaging,hypertrophic cardiomyopathy,cardiovascular magnetic resonance,myocardial architecture,laminar structure,sheet and shear layers,diastolic dysfunction

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