Purpose: To investigate myocardial infarction (MI), late gadolinium (Gd) enhancement (LGE), cardiovascular magnetic resonance imaging (CMRI) is used as the current gold standard for the in vivo diagnosis in patients and preclinical studies. While inversion recovery (IR) fast gradient echo LGE imaging is the preferred technique at clinical field strengths it remains to be investigated which is the best sequence at higher field strength. We therefore compared the IR technique against cine fast low shot angle (cine‐FLASH) for the quantification of MI size in mice at 7T in vivo.Materials and Methods: Five mice were used to optimize cine‐FLASH and IR parameters. Nine mice were subsequently imaged with optimized parameters using both techniques 2–3 days after MI and ≈30 minutes post Gd injection.Results: The difference in infarct size values was within 3.3% between the two CMRI techniques and within 7.5% of histological values by Bland–Altman analysis. Contrast‐to‐noise‐ratio between infarcted and normal tissue as well as blood was higher for cine‐FLASH with the additional benefit of a 2‐time‐fold shorter scan time than with the IR method. Furthermore, left ventricular function/volumes could be calculated from cine‐FLASH images before as well as after Gd injection.Conclusion: In conclusion, cine‐FLASH LGE MRI represents an attractive alternative to IR LGE MRI for infarct size assessment in mice at high field strengths because it provides similar accuracy while being more robust, faster, and less user dependent. J. Magn. Reson. Imaging 2010;32:878–886.

Background: Well‐defined inflammation, proliferation, and maturation phases orchestrate the remodeling of the injured myocardium after myocardial infarction ( MI ) by controlling the formation of new extracellular matrix. The extracellular matrix consists mainly of collagen but also fractions of elastin. It is thought that elastin is responsible for maintaining elastic properties of the myocardium, thus reducing the risk of premature rupture. An elastin/tropoelastin–specific contrast agent (Gd‐ ESMA ) was used to image tropoelastin and mature elastin fibers for in vivo assessment of extracellular matrix remodeling post‐ MI . Methods and Results: Gd‐ ESMA enhancement was studied in a mouse model of myocardial infarction using a 7 T MRI scanner and results were compared to those achieved after injection of a nonspecific control contrast agent, gadolinium‐diethylenetriamine pentaacetic acid (Gd‐ DTPA ). In the infarcted tissue, Gd‐ ESMA uptake (measured as R1 relaxation rate) steadily increased from day 3 to day 21 as a result of the synthesis of elastin/tropoelastin. R1 values were in good agreement with histological findings. A similar R1 behavior was observed in the remote myocardium. No mature cross‐linked elastin was found at any time point. In contrast, Gd‐ DTPA uptake was only observed in the infarct with no changes in R1 values between 3 and 21 days post‐ MI . Conclusions: We demonstrate the feasibility of in vivo imaging of extracellular matrix remodeling post‐ MI using a tropoelastin/elastin binding MR contrast agent, Gd‐ ESMA . We found that tropoelastin is the main contributor to the increased MRI signal at late stages of MI where its augmentation in areas of infarction was in good agreement with the R1 increase.

Cardiomyopathies are complex heart muscle diseases that can be inherited or acquired. Dilated cardiomyopathy can result from mutations in LMNA, encoding the nuclear intermediate filament proteins lamin A/C. Some LMNA mutations lead to accumulation of the lamin A precursor, prelamin A, which is disease causing in a number of tissues, yet its impact upon the heart is unknown. Here, we discovered myocardial prelamin A accumulation occurred in a case of dilated cardiomyopathy, and we show that a potentially novel mouse model of cardiac-specific prelamin A accumulation exhibited a phenotype consistent with inflammatory cardiomyopathy, which we observed to be similar to HIV-associated cardiomyopathy, an acquired disease state. Numerous HIV protease therapies are known to inhibit ZMPSTE24, the enzyme responsible for prelamin A processing, and we confirmed that accumulation of prelamin A occurred in HIV ⁺ patient cardiac biopsies. These findings (a) confirm a unifying pathological role for prelamin A common to genetic and acquired cardiomyopathies; (b) have implications for the management of HIV patients with cardiac disease, suggesting protease inhibitors should be replaced with alternative therapies (i.e., nonnucleoside reverse transcriptase inhibitors); and (c) suggest that targeting inflammation may be a useful treatment strategy for certain forms of inherited cardiomyopathy.

Smart radiotherapy biomaterials (SRBs) present a new opportunity to enhance image-guided radiotherapy while replacing routinely used inert radiotherapy biomaterials like fiducials. In this study the potential of SRBs loaded with gadolinium-based nanoparticles (GdNPs) is investigated for magnetic resonance imaging (MRI) contrast. GdNP release from SRB is quantified and modelled for accurate prediction. SRBs were manufactured similar to fiducials, with a cylindrical shell consisting of poly(lactic-co-glycolic) acid (PLGA) and a core loaded with GdNPs. Magnetic resonance imaging (MRI) contrast was investigated at 7T in vitro (in agar) and in vivo in subcutaneous tumors grown with the LLC1 lung cancer cell line in C57/BL6 mice. GdNPs were quantified in-phantom and in tumor and their release was modelled by the Weibull distribution. Gd concentration was linearly fitted to the R₁ relaxation rate with a detection limit of 0.004 mmol/L and high confidence level (R² = 0.9843). GdNP loaded SRBs in tumor were clearly visible up to at least 14 days post-implantation. Signal decrease during this time showed GdNP release in vivo, which was calculated as 3.86 ± 0.34 µg GdNPs release into the tumor. This study demonstrates potential and feasibility for SRBs with MRI-contrast, and sensitive GdNP quantification and release from SRBs in a preclinical animal model. The feasibility of monitoring nanoparticle (NP) concentration during treatment, allowing dynamic quantitative treatment planning, is also discussed.

Myocardial infarction (MI) results in adverse cardiac remodeling leading to heart failure and increased mortality. Experimental mouse models of MI are extensively used to identify mechanisms underlying adverse remodeling, but the extent of remodeling that occurs may be highly variable and can limit the utility to discover new disease pathways. The ability to predict the development of significant late post-MI remodeling would be invaluable in conducting such studies by increasing throughput and efficiency. This study aimed to identify potential thresholds of cardiac magnetic resonance imaging (MRI) parameters measured early after murine MI that would predict the development of significant adverse remodeling at 4 wk. MI was achieved by permanent coronary ligation and animals (n = 84) were followed up for 4 wk subsequently. MRI was used to assess left ventricular (LV) volumes, mass and ejection fraction, as well as infarct size (IS). Late gadolinium enhancement cine-MRI was performed at 2 days with standard cine-MRI at 30 days post-MI. Utilizing multiple logistic regression, we found that IS >36%, at 2 days post-MI, was the overall best single predictor of adverse remodeling at 30 days (sensitivity 80.7%, specificity 88.9%; C-statistic of 0.939 from receiver-operating curve analysis). LV end-systolic volume (LVESV) >32 μl was also an excellent predictor comparable to IS. The combination of IS >36% and/or LVESV >32 μl provided the highest predictive values for late adverse remodeling among multiple predictors. This study demonstrates that MRI-based estimation of IS and ESV during the acute phase of murine MI are good predictors of subsequent adverse remodeling that may aid experimental design.

Purpose: To investigate a very small iron‐oxide particle (VSOP) in a mouse model of acute ischemia‐reperfusion to access the mechanism of such particles in areas of myocardial inflammation.Materials and Methods: Animals were injected with VSOP at several time points, in a mouse model of acute myocardial infarction (MI), before and after MI. MRI was used to localize areas of VSOP enhancement, evaluate VSOP areas extension, and determine the related T2* values. Histology, electron microscopy, macrophage counting, and Evan's Blue staining were also performed.Results: We found that areas of VSOP uptake decreased from 1 to 8 days post‐MI while the related T2* values increased. T2* and VSOP areas, defined from MRI data, correlated well between 1 and 3 days post‐MI but not at 7 days after injection. Histological analysis and electron microscopy showed colocalization of macrophages with areas of VSOP staining. However, there was no correlation between number of macrophages and the extension of the VSOP areas achieved by MR. We found that only areas of increased permeability (assessed by Evan's Blue staining) showed colocalization of macrophages and VSOP uptake.Conclusion: This study demonstrates that VSOP allows the assessment of myocardial inflammation associated with increased permeability during infarct healing in a mouse model of ischemia‐reperfusion. J. Magn. Reson. Imaging 2014;39:598–608. © 2013 Wiley Periodicals, Inc.