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Background
Myocardial fibrosis is a common hallmark of many diseases of the heart. Late gadolinium enhanced MRI is a powerful tool to image replacement fibrosis after myocardial infarction (MI). Interstitial fibrosis can be assessed indirectly from an extracellular volume fraction measurement using contrast-enhanced T1 mapping. Detection of short...
Citations
... In addition, another study demonstrated the feasibility of using a T2 Ã -weighted 3-D radial MRI sequence for the assessment of cardiac fibrosis in mice. This study showed that the T2 Ã values were significantly lower in fibrotic hearts than in healthy hearts (67). The major drawback for T2 Ã mapping is the influence of field inhomogeneities that induces a false positive area for fibrosis at the lungheart interface, this ultimately increases the difficulty of analysis (81). ...
Cardiovascular magnetic resonance (CMR) imaging has become an essential technique for the assessment of cardiac function and morphology, and is now routinely used to monitor disease progression and intervention efficacy in the clinic. Cardiac fibrosis is a common characteristic of numerous cardiovascular diseases and often precedes cardiac dysfunction and heart failure. Hence, the detection of cardiac fibrosis is important for both early diagnosis and the provision of guidance for interventions/therapies. Experimental mouse models with genetically and/or surgically induced disease have been widely used to understand mechanisms underlying cardiac fibrosis, and to assess new treatment strategies. Improving the appropriate applications of CMR to mouse studies of cardiac fibrosis has the potential to generate new knowledge, and more accurately examine the safety and efficacy of anti-fibrotic therapies. In this review, we provide 1) a brief overview of different types of cardiac fibrosis, 2) general background on magnetic resonance imaging (MRI), 3) a summary of different CMR techniques used in mice for the assessment of cardiac fibrosis including experimental and technical considerations (contrast agents and pulse sequences), and 4) provide an overview of mouse studies that have serially monitored cardiac fibrosis during disease progression and/or therapeutic interventions. Clinically established CMR protocols have advanced mouse CMR for the detection of cardiac fibrosis, and there is hope that discovery studies in mice will identify new anti-fibrotic therapies for patients; highlighting the value of both reverse translation and bench-to-bedside research.
... Unfortunately, the requirement for gadolinium-based contrast agents which is contraindicated in patients with renal failure and hypersensitivity is the main limitation of the technique [20]. Relatively long scanning time and requiring the precision of appropriate inversion time are other limitations of contrast-enhanced myocardial mapping and tissue characterization techniques [21]. Thus, an alternative imaging tool to assess myocardial disease without needing gadolinium-based contrast agents would be preferable in patients with multi-organ dysfunction and renal insufficiency. ...
... T2* mapping is the current method of choice for the non-invasive assessment of cardiac iron deposition and the evaluation of the response to the treatment with chelation therapy and recommended imaging tool in practically all clinical guidelines relating to iron overload treatment [22]. For all that, recent studies have focused on T2* mapping for post-revascularization hemorrhage [23,24], hypertrophic cardiomyopathy [25,26], or myocardial fibrosis [21]. On the other hand, T2* mapping for non-COVID-19 myocarditis has become an area of great interest [27,28]. ...
... Recent studies have demonstrated that T1 mapping with prolonged T1 relaxation time is a useful diagnostic tool in the assessment of fibrosis and interstitial remodeling of the myocardium [45]. However, the current evidence conflicts with recent studies reporting decreased T2* values in hypertrophic cardiomyopathy [26,46] or in post-myocardial infarction [21], especially those who had myocardial fibrosis or fibrotic segments. The result of our study with decreased T2* value without increased native-T1 value is speculative. ...
The coronavirus disease of 2019 (COVID-19)-related myocardial injury is an increasingly recognized complication and cardiac magnetic resonance imaging (MRI) has become the most commonly used non-invasive imaging technique for myocardial involvement. This study aims to assess myocardial structure by T2*-mapping which is a non-invasive gold-standard imaging tool for the assessment of cardiac iron deposition in patients with COVID-19 pneumonia without significant cardiac symptoms. Twenty-five patients with COVID-19 pneumonia and 20 healthy subjects were prospectively enrolled.Cardiac volume and function parameters, myocardial native-T1, and T2*-mapping were measured. The association of serum ferritin level and myocardial mapping was analyzed. There was no difference in terms of cardiac volume and function parameters. The T2*-mapping values were lower in patients with COVID-19 compared to controls (35.37 [IQR 31.67–41.20] ms vs. 43.98 [IQR 41.97–46.88] ms; p < 0.0001), while no significant difference was found in terms of native-T1 mapping value(p = 0.701). There was a positive correlation with T2*mapping and native-T1 mapping values (r = 0.522, p = 0.007) and negative correlation with serum ferritin values (r = − 0.653, p = 0.000), while no correlation between cardiac native-T1 mapping and serum ferritin level. Negative correlation between serum ferritin level and T2*-mapping values in COVID-19 patients may provide a non-contrast-enhanced alternative to assess tissue structural changes in patients with COVID-19. T2*-mapping may provide a non-contrast-enhanced alternative to assess tissue alterations in patients with COVID-19. Adding T2*-mapping cardiac MRI in patients with myocardial pathologies would improve the revealing of underlying mechanisms. Further in vivo and ex vivo animal or human studies designed with larger patient cohorts should be planned.
... Beyond the observed mean variations already discussed, individual variations observed in T2 and T2* values (Fig. 4 for T2* and Fig. 5 for T2) along such long-distance running are also probably determined by a complex system of regulatory mechanisms including individual response to inflammatory processes at each compartment level, and the intrinsic differences between T2 and T2* mechanisms can probably provide further insights. Indeed, T2* mapping differentiates from T2 mapping by its ability to characterize the relaxation of the transverse magnetization that is influenced by macroscopic (inhomogeneities of the magnetic field) and mesoscopic (structure of the tissue) magnetic field inhomogeneities (44)(45)(46)(47)(48). For example, reduced T2* values have already shown the potential to describe structural alterations suggestive of ischemic alterations, collagen areas or hemorrhage, for instance, in myocardium and extracardiac tissues (49,50). ...
... For example, reduced T2* values have already shown the potential to describe structural alterations suggestive of ischemic alterations, collagen areas or hemorrhage, for instance, in myocardium and extracardiac tissues (49,50). According to this, histopathologic substrates of T2* and a correlation of T2* to flow analyses have been demonstrated (45)(46)(47)(48)51). Recently, reduced T2* values have been described in a group of hypertrophic cardiomyopathy patients potentially triggered through relative ischemia (52). ...
Extreme ultra-endurance races are growing in popularity but their effects on skeletal muscles remain mostly unexplored. This longitudinal study explores physiological changes in mountain ultramarathon (MUM) athletes' quadriceps using quantitative magnetic resonance imaging (qMRI) coupled with serological biomarkers. The study aimed to monitor the longitudinal effect of the race and recovery, and to identify local inflammatory and metabolic muscle responses by codetection of biological markers.
Methods:
An automatic image processing framework was designed to extract imaging-based biomarkers from qMRI acquisitions of the upper legs of 20 finishers at three time points. The longitudinal impact of the race was demonstrated by analyzing the image markers with dedicated biostatistical analysis.
Results:
Our framework allows a reliable calculation of statistical data not only inside the whole quadriceps volume but also within each individual muscle heads. Local changes in MRI parameters extracted from quantitative maps were described and found significantly correlated with principal serological biomarkers of interest. A decrease in the PDFF after the race and a stable paramagnetic susceptibility value were found. Pairwise post hoc tests suggested that the recovery process differs among the muscle heads.
Conclusion:
This longitudinal study conducted during a prolonged and extreme mechanical stress, showed that quantitative MRI-based markers of inflammation and metabolic response can detect local changes related to the prolonged exercise, with differentiated involvement of each head of the quadriceps muscle as expected in such eccentric load. Consistent and efficient extraction of the local biomarkers enables to highlight interplay/interactions between blood and MRI biomarkers. This work indeed proposes an automatized analytic framework to tackle the time consuming and mentally exhausting segmentation task of muscle heads in large multi-time-points cohorts.
... Injured muscles also presented reduced long-T 2 *, in agreement with observations in fibrotic myocardium 10 . However, long-T 2 * did not correlate with collagen fraction. ...
Fibrosis is a key pathological feature in muscle disorders, but its quantification mainly relies on histological and biochemical assays. Muscle fibrosis most frequently is entangled with other pathological processes, as cell membrane lesions, inflammation, necrosis, regeneration, or fatty infiltration, making in vivo assessment difficult. Here, we (1) describe a novel mouse model with variable levels of induced skeletal muscle fibrosis displaying minimal inflammation and no fat infiltration, and (2) report how fibrosis affects non-invasive metrics derived from nuclear magnetic resonance (NMR) and ultrasound shear-wave elastography (SWE) associated with a passive biomechanical assay. Our findings show that collagen fraction correlates with multiple non-invasive metrics. Among them, muscle stiffness as measured by SWE, T 2 , and extracellular volume (ECV) as measured by NMR have the strongest correlations with histology. We also report that combining metrics in a multi-modality index allowed better discrimination between fibrotic and normal skeletal muscles. This study demonstrates that skeletal muscle fibrosis leads to alterations that can be assessed in vivo with multiple imaging parameters. Furthermore, combining NMR and SWE passive biomechanical assay improves the non-invasive evaluation of skeletal muscle fibrosis and may allow disentangling it from co-occurring pathological alterations in more complex scenarios, such as muscular dystrophies.
... A contrario, une diminution du T1 peut provenir d'une surcharge lipidique ou ferrique dans le tissu myocardique. [32]. Chez les souris ayant eu un Infarctus du Myocarde (MI), la zone d'infarctus était caractérisée par une décroissance T2* plus rapide par rapport aux tissus sains. ...
L’Imagerie cardio-thoracique par Résonance Magnétique est encore aujourd’hui un véritable défi. La difficulté réside dans la nécessité d’acquérir des images avec de fortes résolutions spatiales et temporelles sur des zones en mouvement, et ce, en un temps limité. Dans le but de s’affranchir des mouvements cardio-respiratoires, la solution la plus communément employée consiste à ne pas acquérir de données pendant l’inspiration et l’expiration ou à les écarter. Cette solution est aujourd’hui la plus communément appliquée, mais elle entraine une augmentation significative du temps d’acquisition total (jusqu’à 50%). Au vu de ces principales limitations, le travail mené au cours de cette thèse possède un objectif général : réduire les temps d’acquisition d’images cardio-thoraciques chez le petit animal et améliorer leur qualité (précision, contraste et résolution). Des séquences IRM radiale et à temps d’écho ultra-court (UTE) ainsi que des algorithmes de reconstruction ont été développés, pour obtenir des images cardio-thoraciques en 4D (3D-temporel) dans des temps d’acquisition court.Ce travail de recherche a été structuré autour de deux axes principaux.I - Développer une méthode d’interpolation des données cardiaques pendant les intervalles de mouvement respiratoire. Pour la première fois sur le petit animal, l’impact du mouvement respiratoire de la souris sur la position de son cœur a été précisément analysé. Un algorithme a ensuite été développé afin d’interpoler les données cardiaques pendant les intervalles de respiration. De manière novatrice, la reconstruction d’images cardiaques en fonction des battements du cœur utilisant la totalité des données acquises a été rendue possible. Ce protocole, intégré à la séquence UTE, a été testé, validé et comparé aux méthodes standards sur des souris saines puis il a été appliqué sur des pathologies cardio-pulmonaires à travers différentes collaborations. En conclusion, des images 4D du cœur battant de souris ont pu être acquises en 1’45 avec de fortes résolutions spatiale et temporelle (176m isotropique et 5ms / image), permettant de mesurer les paramètres cardiaques nécessaires à la détection, l’analyse ainsi que le suivi de différentes pathologies.II – Réduire le temps d’acquisition de l’imagerie cardio-thoracique 4D et améliorer son contraste : Application à l’angiographie pulmonaire. Une séquence Radiale 3D avec auto-synchronisation des mouvements a été développée avec les mêmes paramètres que l’UTE, afin de réduire davantage son temps d’acquisition. Les deux séquences ont été appliquées sur les poumons afin de reconstruire des angiographies pulmonaires 3D de haute résolution en fonction de la respiration. Une technique de suppression de graisse accélérée a été implémentée et permet d’améliorer le contraste entre les vaisseaux et les bronches, tout en maintenant une durée d’acquisition raisonnable. En conclusion, ces travaux ont permis d’optimiser les séquences UTE et Radiale et d’évaluer leur avantage en angiographie pulmonaire. Les résultats sont prometteurs et ouvrent des perspectives concernant la segmentation et la quantification du réseau vasculaire pulmonaire.En conclusion, les séquences et algorithmes développés au cours de ce projet ont permis de réduire considérablement les temps d’acquisitions d’imagerie cardio-thoracique 4D et ouvrent de ce fait des perspectives pour l’étude de modèles animaux ou pour un transfert en imagerie clinique.Mots clés : IRM ; Cardio-thoracique ; 4D ; Séquence ; Développement
... Over 10-fold decreased myocardial T2 * (0.7 ± 0.2 ms) was observed in the iron-loaded thalassemia group, which was consistent with histological results. van Nierop et al. [163] reported reduced T2 * value in myocardial infarction (MI) and transverse aortic constriction (TAC) mice using an ECG-triggered T2 * -weighted 3D center-out radial sequence with TE ranging from 21 µs to 4 ms. T2 * -shortening contrast agents, such as iron oxide nanoparticles (IONPs), have been used to exploit T2 * contrast in mouse cardiovascular system [164,165]. ...
... This yields a rather low specificity of the IONP approach. Similar to SWIFT, ultrashort echo time (UTE) techniques have been used for providing endogenous T2 * contrast [163,170]. ...
Cardiovascular magnetic resonance (CMR) imaging has become an accurate and versatile imaging modality to visualize the cardiovascular system in normal or abnormal conditions. In preclinical research, small rodent animal models of human cardiovascular diseases are frequently used to investigate the basic underlying mechanism of normal and abnormal cardiac function and for monitoring the disease progression under therapy. Technical improvements have enabled the transfer of CMR to small animal research, and as such made this non-invasive technique available to provide insights into cardiac morphology, function, perfusion, and pathophysiology in small animal cardiac disease models. This article reviews the basic technical approaches to in vivo small animal magnetic resonance imaging and its variants for the most promising applications.
... 38 Moreover, MR parameters such as T 2 and T 2 * in infarcted/fibrotic cardiac tissue have demonstrated that MR parameters are linearly related to collagen content and tissue fibrosis based on staining for collagen content. 39,40 In our study, we have demonstrated that with increase in tumour burden, T 2 of skeletal muscles decreases. Moreover, a strong negative correlation between tumour size and GA muscle T 2 has been demonstrated. ...
Background
Cancer cachexia is a multifactorial wasting syndrome that is characterized by the loss of skeletal muscle mass and weakness, which compromises physical function, reduces quality of life, and ultimately can lead to mortality. Experimental models of cancer cachexia have recapitulated this skeletal muscle atrophy and consequent decline in muscle force‐generating capacity. We address these issues in a novel transgenic mouse model Kras, Trp53, and Pdx‐1‐Cre (KPC ) of pancreatic ductal adenocarcinoma using multi‐parametric magnetic resonance measures.
Methods
KPC mice (n = 10) were divided equally into two groups (n = 5 per group) depending on the size of the tumour, that is, tumour size <250 and >250 mm³. Using multi‐parametric magnetic resonance measures, we demonstrated the changes in the gastrocnemius muscle at the microstructural level. In addition, we evaluated skeletal muscle contractile function in KPC mice using an in vivo approach.
Results
Increase in tumour size resulted in decrease in gastrocnemius maximum cross‐sectional area, decrease in T2 relaxation time, increase in magnetization transfer ratio, decrease in mean diffusivity, and decrease in radial diffusivity of water across the muscle fibres. Finally, we detected significant decrease in absolute and specific force production of gastrocnemius muscle with increase in tumour size.
Conclusions
Our findings indicate that increase in tumour size may cause alterations in structural and functional parameters of skeletal muscles and that MR parameters may be used as sensitive biomarkers to non‐invasively detect structural changes in cachectic muscles.
... 6 13-15 In particular, T2* mapping has proven feasibility to detect ischaemic segments in extracardiac organs but also in myocardial infarction and coronary artery disease (CAD). [15][16][17][18][19][20][21] Reduced T2* values have been described in patients with HCM potentially triggered through relative ischaemia. 22 As relative ischaemia seems to be related to a worse prognosis, the aim of this study was to assess the relation of myocardial T2* mapping by CMR with the occurrence of arrhythmia or heart failure (HF) in patients with HCM. ...
... 15 18 21 According to this, histopathological substrates of T2* and a correlation of T2* to flow analyses have been studied. 16 17 19 20 30 Recently, reduced T2* values have been described in a group of patients with HCM potentially triggered through relative ischaemia. 22 Another explanation for the reduction of T2* values could be that in areas of reduced perfusion, oxymyoglobin and haemoglobin as oxygen suppliers are decreased, whereas deoxymyoglobin and haemoglobin are increased. ...
Background
Hypertrophic cardiomyopathy (HCM) is associated with an increased risk of adverse cardiac events. Beyond classic risk factors, relative myocardial ischaemia and succeeding myocardial alterations, which can be detected using either contrast agents or parametric mapping in cardiovascular magnetic resonance (CMR) imaging, have shown an impact on outcome in HCM. CMR may help to risk stratify using parametric T2* mapping. Therefore, the aim of the present study was to evaluate the association of T2* values or fibrosis with cardiovascular events in HCM.
Methods
The relationship between T2* with supraventricular, ventricular arrhythmia or heart failure was retrospectively assessed in 91 patients with HCM referred for CMR on a 1.5T MR imaging system. Fibrosis as a reference was added to the model. Patients were subdivided into groups according to T2* value quartiles.
Results
47 patients experienced an event of ventricular arrhythmia, 25 of atrial fibrillation/flutter and 17 of heart failure. T2*≤28.7 ms yielded no association with ventricular events in the whole HCM cohort. T2* of non-obstructive HCM showed a significant association with ventricular events in univariate analysis, but not in multivariate analysis. For the combined endpoint of arrhythmic events, there was already an association for the whole HCM cohort, but again only in univariate analyses. Fibrosis stayed the strongest predictor in all analyses. There was no association for T2* and fibrosis with heart failure.
Conclusions
Decreased T2* values by CMR only provide a small association with arrhythmic events in HCM, especially in non-obstructive HCM. No information is added for heart failure.
... Although, the extent of fibrosis also showed a similar positive correlation with T2*, this was likely to be confounded by the linear correlation between the severity of necrosis and fibrosis at this phase of myocarditis. It is more reasonable that increased T2* reflects necrosis rather than fibrosis, considering that necrosis is dominant at this phase and fibrosis, containing less water content, would be expected to decrease T2* [41]. T2* reflects both T2 and magnetic field heterogeneity, which is affected by the tissue microstructure [42]. ...
Abstract Background The diagnostic utility of cardiovascular magnetic resonance (CMR) is limited during the early stages of myocarditis. This study examined whether ferumoxytol-enhanced CMR (FE-CMR) could detect an earlier stage of acute myocarditis compared to gadolinium-enhanced CMR. Methods Lewis rats were induced to develop autoimmune myocarditis. CMR (3 T, GE Signa) was performed at the early- (day 14, n = 7) and the peak-phase (day 21, n = 8) of myocardial inflammation. FE-CMR was evaluated as % myocardial dephasing signal loss on gradient echo images at 6 and 24 h (6 h- & 24 h-FE-CMR) following the administration of ferumoxytol (300μmolFe/kg). Pre- and post-contrast T2* mapping was also performed. Early (EGE) and late (LGE) gadolinium enhancement was obtained after the administration of gadolinium-DTPA (0.5 mmol/kg) on day 14 and 21. Healthy rats were used as control (n = 6). Results Left ventricular ejection fraction (LVEF) was preserved at day 14 with inflammatory cells but no fibrosis seen on histology. EGE and LGE at day 14 both showed limited myocardial enhancement (EGE: 11.7 ± 15.5%; LGE: 8.7 ± 8.7%; both p = ns vs. controls). In contrast, 6 h-FE-CMR detected extensive myocardial signal loss (33.2 ± 15.0%, p = 0.02 vs. EGE and p
... 44 More recently, van Nierop and colleagues investigated whether T 2 * weighted radial sequences could directly visualize the presence of both replacement and interstitial fibrosis. 45 In a mice model with MI (replacement fibrosis), transverse aortic constriction (diffuse fibrosis) and controls, the authors performed 3D center-out radial T 2 * weighted imaging with varying TE in vivo and ex vivo (TE = 21 μs-4 ms) and compared findings to histology. Long-TE images were subtracted from images with a short-TE to obtain ΔUTE signal. ...
... In vivo signal difference between long and short-TE. 45 In vivo signal difference between long and short-TE, in control, post-MI and TAC mouse hearts. The signal difference between the short-TE (21 μs) and long-TE images (1.429 ms) is larger for remote and infarct tissue in post-MI hearts, and in TAC hearts, compared to control hearts. ...
... Error bars indicate SD. Image reprinted from van Nierop et al. 45 TE, echo time; TAC, transverse aortic constriction. BJR Cardiovascular ultrashort time to echo imaging UTE, as a contrastless method, could also be used to monitor the progressive decline in aortic function that is associated with aging, and occurs in females and males of every ethnicity. ...
Increased collagen, or fibrosis, is an important marker of disease and may improve identification of patients at risk. In addition, fibrosis imaging may play an increasing role in guiding therapy and monitoring its effectiveness. Magnetic Resonance Imaging (MRI) is the most frequently used modality to detect, visualize and quantify fibrosis non-invasively. However, standard MRI techniques used to phenotype cardiac fibrosis such as delayed enhancement and extracellular volume determination by T1 mapping, require the administration of gadolinium-based contrast and are particularly difficult to use in patients with cardiac devices such as pacemakers and automatic defibrillators. Therefore, such methods are limited in the serial evaluation of cardiovascular fibrosis as part of chronic disease monitoring. A method to directly measure collagen amount could be of great clinical benefit. In the current review we will discuss the potential of a novel MR technique, ultrashort echo time (UTE) MR, for fibrosis imaging. Although UTE imaging is successfully applied in other body areas such as musculoskeletal applications, there is very limited experience so far in the heart. We will review the established methods and currently available literature, discuss the technical considerations and challenges, show preliminary in vivo images and provide a future outlook on potential applications of cardiovascular UTE.
