Longitudinal rotating frame relaxation time measurements in infarcted mouse myocardium in vivo

Musthafa, Haja-Sherief N.; Dragneva, Galina; Lottonen, Line; Merentie, Mari; Petrov, L. Yu.; Heikura, Tommi; Ylä-Herttuala, Elias; Ylä‐Herttuala, Seppo; Gröhn, Olli; Liimatainen, Timo

doi:10.1002/mrm.24382

Cited by 38 publications

(64 citation statements)

References 31 publications

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“…These results correlate well with the increased fibrosis visualized using histology. In a previous study, a similar increase in T 1ρ was found after 7 days of left anterior descending artery occlusion in mice . Together, these results indicate that T 1ρ acts as a general marker for fibrosis which is more widely applicable than for myocardial infarcted tissue only.…”

Section: Discussionsupporting

confidence: 78%

The follow‐up of progressive hypertrophic cardiomyopathy using magnetic resonance rotating frame relaxation times

et al. 2017

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Magnetic resonance rotating frame relaxation times are an alternative non-contrast agent choice for the diagnosis of chronic myocardial infarct. Fibrosis typically occurs in progressive hypertrophic cardiomyopathy. Fibrosis has been imaged in myocardial infarcted tissue using rotating frame relaxation times, which provides the possibility to follow up progressive cardiomyopathy without contrast agents. Mild and severe left ventricular hypertrophy were induced in mice by transverse aortic constriction, and the longitudinal rotating frame relaxation times (T ) and relaxation along the fictitious field (T , T ) were measured at 5, 10, 24, 62 and 89 days after transverse aortic constriction in vivo. Myocardial fibrosis was verified using Masson's trichrome staining. Increases in the relative relaxation time differences of T , together with T and T , between fibrotic and remote tissues over time were observed. Furthermore, T and T showed higher relaxation times overall in fibrotic tissue than T . Relaxation time differences were highly correlated with an excess of histologically verified fibrosis. We found that T and T are more sensitive than T to hypertrophic cardiomyopathy-related tissue changes and can serve as non-invasive diagnostic magnetic resonance imaging markers to follow up the mouse model of progressive hypertrophic cardiomyopathy.

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Section: Discussionsupporting

confidence: 78%

The follow‐up of progressive hypertrophic cardiomyopathy using magnetic resonance rotating frame relaxation times

et al. 2017

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“…In our model, no fibrosis was detected on histological analysis, in comparison with a myocardial infarction study on mice in which T 1ρ was found to be associated with fibrosis. 12 Both T 2 and T 1ρ showed similar changes after ischemia, which implies that the processes causing these changes are mainly close to the frequency of~1250 Hz at which T 1ρ is sensitive, and no substantial processes, at least not opposing ones, occur at lower frequencies. T 2 and T 1ρ also revealed a significant difference (p < 0.01) between relaxation times in early regenerative areas compared with areas of normal tissue and late regeneration.…”

Section: Discussionmentioning

confidence: 76%

“…Post‐ischemic increases in T 2 have also been reported in previous studies of hind limb ischemia and ischemia–reperfusion injury, but only a few studies have implemented T 1ρ in skeletal muscle imaging. In our model, no fibrosis was detected on histological analysis, in comparison with a myocardial infarction study on mice in which T 1ρ was found to be associated with fibrosis . Both T 2 and T 1ρ showed similar changes after ischemia, which implies that the processes causing these changes are mainly close to the frequency of ~1250 Hz at which T 1ρ is sensitive, and no substantial processes, at least not opposing ones, occur at lower frequencies.…”

Section: Discussionmentioning

confidence: 99%

T₂, T_1ρ and T_RAFF4 detect early regenerative changes in mouse ischemic skeletal muscle

et al. 2018

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The identification of areas with regenerative potential in ischemic tissues would allow the targeting of treatments supporting tissue recovery. The regeneration process involves the activation of several cellular and molecular responses which could be detected using magnetic resonance imaging (MRI). However, to date, magnetic resonance (MR) relaxation parameters have received little attention in the diagnosis and follow-up of limb ischemia. The purpose of this study was to evaluate the feasibility of different MRI relaxation and diffusion tensor imaging parameters in the detection of areas showing early signs of regeneration in ischemic mouse skeletal muscles. T and T relaxation time constants, together with T , T and diffusion tensor imaging, were evaluated to differentiate areas of regeneration in a mouse hind limb ischemia model before and 0, 1, 4, 7, 14 and 30 days after ischemia. All the measured relaxation times were longer in the areas of early regeneration compared with normal muscle tissue. The relaxation times increased after ischemia in the ischemic muscles, reaching a maximum at 4-7 days after occlusion, coinciding with the appearance of early signs of regeneration. Fractional anisotropy decreased significantly (p < 0.05) on days 1-4, whereas mean diffusivity, λ and λ decreased later, starting at day 7 after ischemia compared with the pre-operational time point. The percentages of areas with different tissue morphologies were determined based on histological analysis of the ischemic muscle cross-sections, and correlations between the percentages obtained and different relaxation times were calculated. The highest correlation between relaxation times and histology was achieved with T , T and T (R = 0.96, R = 0.92 and R = 0.84, respectively, p < 0.01) Early regenerative changes were visible using T , T and T MR relaxation time constants in skeletal muscle after ischemia. These markers could potentially be used for the identification of targets for therapies supporting muscle regeneration after ischemic injury.

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“…The mFI imaging is based on T 1 ρ dispersion contrast, rather than the absolute T 1 ρ contrast. The latter has been reported by several groups to show up to a 1-fold higher T 1 ρ value for myocardial scar tissue induced by MI [12,13,20]. For other regions with less collagen content, such as the border zone of the infarct, the amount of increase in T 1 ρ is much less, making the distinction and quantification of differences in fibrosis more problematic.…”

Section: Discussionmentioning

confidence: 80%

“…This contrast approach measures spin-lattice relaxation time in the rotating frame at a spin-lock amplitude B 1 [11]. In myocardial muscle, T 1 ρ increased up to 2-fold in regions of chronic, non-reperfused MI (primarily replacement fibrosis or scar), in comparison with remote normal myocardial tissue [12,13]. A recent report by van Oorschot et al demonstrated a good correlation of myocardial T 1 ρ and ECV values in 20 patients with dilated cardiomyopathy (Pearson r = 0.66) [14].…”

Section: Introductionmentioning

confidence: 99%

A non-contrast CMR index for assessing myocardial fibrosis

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Muccigrosso

et al. 2017

Magnetic Resonance Imaging

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Purpose: Safe, sensitive, and non-invasive imaging methods to assess the presence, extent, and turnover of myocardial fibrosis are needed for early stratification of risk in patients who might develop heart failure after myocardial infarction. We describe a non-contrast cardiac magnetic resonance (CMR) approach for sensitive detection of myocardial fibrosis using a canine model of myocardial infarction and reperfusion. Methods: Seven dogs had coronary thrombotic occlusion of the left anterior descending coronary arteries followed by fibrinolytic reperfusion. CMR studies were performed at 7 days after reperfusion. A CMR spin-locking T1ρ mapping sequence was used to acquire T1ρ dispersion data with spin-lock frequencies of 0 and 511 Hz. A fibrosis index map was derived on a pixel-by-pixel basis. CMR native T1 mapping, first-pass myocardial perfusion imaging, and post-contrast late gadolinium enhancement imaging were also performed for assessing myocardial ischemia and fibrosis. Hearts were dissected after CMR for histopathological staining and two myocardial tissue segments from the septal regions of adjacent left ventricular slices were qualitatively assessed to grade the extent of myocardial fibrosis. Results: Histopathology of 14 myocardial tissue segments from septal regions was graded as grade 1 (fibrosis area, <20% of a low power field, n = 9), grade 2 (fibrosis area, 20–50% of field, n = 4), or grade 3 (fibrosis area, >50% of field, n = 1). A dramatic difference in fibrosis index (183%, P < 0.001) was observed by CMR from grade 1 to 2, whereas differences were much smaller for T1ρ (9%, P = 0.14), native T1 (5.5%, P = 0.12), and perfusion (−21%, P = 0.05). Conclusion: A non-contrast CMR index based on T1ρ dispersion contrast was shown in preliminary studies to detect and correlate with the extent of myocardial fibrosis identified histopathologically. A non-contrast approach may have important implications for managing cardiac patients with heart failure, particularly in the presence of impaired renal function.

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Longitudinal rotating frame relaxation time measurements in infarcted mouse myocardium in vivo

Cited by 38 publications

References 31 publications

The follow‐up of progressive hypertrophic cardiomyopathy using magnetic resonance rotating frame relaxation times

The follow‐up of progressive hypertrophic cardiomyopathy using magnetic resonance rotating frame relaxation times

T₂, T_1ρ and T_RAFF4 detect early regenerative changes in mouse ischemic skeletal muscle

A non-contrast CMR index for assessing myocardial fibrosis

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Longitudinal rotating frame relaxation time measurements in infarcted mouse myocardium in vivo

Cited by 38 publications

References 31 publications

The follow‐up of progressive hypertrophic cardiomyopathy using magnetic resonance rotating frame relaxation times

The follow‐up of progressive hypertrophic cardiomyopathy using magnetic resonance rotating frame relaxation times

T2, T1ρ and TRAFF4 detect early regenerative changes in mouse ischemic skeletal muscle

A non-contrast CMR index for assessing myocardial fibrosis

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T₂, T_1ρ and T_RAFF4 detect early regenerative changes in mouse ischemic skeletal muscle