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In Vivo Quantification of Myocardial Infarction in Mice Using Micro-CT and a Novel Blood Pool Agent.

ABSTRACT: We herein developed a micro-CT method using the innovative contrast agent ExiTron™ MyoC 8000 to longitudinally monitor cardiac processes in vivo in small animals. Experiments were performed on healthy mice and mice with myocardial infarction inflicted by ligation of the left anterior descending artery. Time-dependent signal enhancement in different tissues of healthy mice was measured and various contrast agent doses were investigated so as to determine the minimum required dose for imaging of the myocardium. Due to its ability to be taken up by healthy myocardium but not by infarct tissue, ExiTron MyoC 8000 enables detection of myocardial infarction even at a very low dose. The signal enhancement in the myocardium of infarcted mice after contrast agent injection was exploited for quantification of infarct size. The values of infarct size obtained from the imaging method were compared with those obtained from histology and showed a significant correlation (R2 = 0.98). Thus, the developed micro-CT method allows for monitoring of a variety of processes such as cardiac remodeling in longitudinal studies.

SUBMITTER: Sawall S

PROVIDER: S-EPMC5662822 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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<i>In Vivo</i> Quantification of Myocardial Infarction in Mice Using Micro-CT and a Novel Blood Pool Agent.

Sawall Stefan S Franke Danielle D Kirchherr Anne A Beckendorf Jan J Kuntz Jan J Maier Joscha J Kraupner Alexander A Backs Johannes J Briel Andreas A Kachelrieß Marc M

Contrast media & molecular imaging 20171016

We herein developed a micro-CT method using the innovative contrast agent ExiTron™ MyoC 8000 to longitudinally monitor cardiac processes <i>in vivo</i> in small animals. Experiments were performed on healthy mice and mice with myocardial infarction inflicted by ligation of the left anterior descending artery. Time-dependent signal enhancement in different tissues of healthy mice was measured and various contrast agent doses were investigated so as to determine the minimum required dose for imagi ...[more]

PMID: 29114173

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Project description:Background: Angiographic detection of thrombus in STEMI is associated with adverse outcomes. However, routine thrombus aspiration failed to demonstrate the anticipated benefit. Hence, management of high coronary thrombus burden remains challenging. We sought to assess for the first time extracted thrombotic material characteristics utilizing micro-computed tomography (micro-CT). Methods: One hundred thirteen STEMI patients undergoing thrombus aspiration were enrolled. Micro-CT was undertaken to quantify retrieved thrombus volume, surface, and density. Correlation of these indices with angiographic and electrocardiographic outcomes was performed. Results: Mean aspirated thrombus volume, surface, and density (±standard deviation) were 15.71 ± 20.10 mm3, 302.89 ± 692.54 mm2, and 3139.04 ± 901.88 Hounsfield units, respectively. Aspirated volume and surface were significantly higher (p < 0.001) in patients with higher angiographic thrombus burden. After multivariable analysis, independent predictors for thrombus volume were reference vessel diameter (RVD) (p = 0.011), right coronary artery (RCA) (p = 0.039), and smoking (p = 0.027), whereas RVD (p = 0.018) and RCA (p = 0.019) were predictive for thrombus surface. Thrombus volume and surface were independently associated with distal embolization (p = 0.007 and p = 0.028, respectively), no-reflow phenomenon (p = 0.002 and p = 0.006, respectively), and angiographically evident residual thrombus (p = 0.007 and p = 0.002, respectively). Higher thrombus density was correlated with worse pre-procedural TIMI flow (p < 0.001). Patients with higher aspirated volume and surface developed less ST resolution (p = 0.042 and p = 0.023, respectively). Conclusions: Angiographic outcomes linked with worse prognosis were more frequent among patients with larger extracted thrombus. Despite retrieving larger thrombus load in these patients, current thrombectomy devices fail to deal with thrombotic material adequately. Further studies of novel thrombus aspiration technologies are warranted to improve patient outcomes. Clinical Trial Registration: QUEST-STEMI trial ClinicalTrials.gov number: NCT03429608 Date of registration: February 12, 2018. The study was prospectively registered.

Project description:BackgroundQuantitative relaxation time measurements by cardiovascular magnetic resonance (CMR) are of paramount importance in contrast-enhanced studies of experimental myocardial infarction. First, compared to qualitative measurements based on signal intensity changes, they are less sensitive to specific parameter choices, thereby allowing for better comparison between different studies or during longitudinal studies. Secondly, T1 measurements may allow for quantification of local contrast agent concentrations. In this study, a recently developed 3D T1 mapping technique was applied in a mouse model of myocardial infarction to measure differences in myocardial T1 before and after injection of a liposomal contrast agent. This was then used to assess the concentration of accumulated contrast agent.Materials and methodsMyocardial ischemia/reperfusion injury was induced in 8 mice by transient ligation of the LAD coronary artery. Baseline quantitative T1 maps were made at day 1 after surgery, followed by injection of a Gd-based liposomal contrast agent. Five mice served as control group, which followed the same protocol without initial surgery. Twenty-four hours post-injection, a second T1 measurement was performed. Local ΔR1 values were compared with regional wall thickening determined by functional cine CMR and correlated to ex vivo Gd concentrations determined by ICP-MS.ResultsCompared to control values, pre-contrast T1 of infarcted myocardium was slightly elevated, whereas T1 of remote myocardium did not significantly differ. Twenty-four hours post-contrast injection, high ΔR1 values were found in regions with low wall thickening values. However, compared to remote tissue (wall thickening > 45%), ΔR1 was only significantly higher in severe infarcted tissue (wall thickening < 15%). A substantial correlation (r = 0.81) was found between CMR-based ΔR1 values and Gd concentrations from ex vivo ICP-MS measurements. Furthermore, regression analysis revealed that the effective relaxivity of the liposomal contrast agent was only about half the value determined in vitro.Conclusions3D cardiac T1 mapping by CMR can be used to monitor the accumulation of contrast agents in contrast-enhanced studies of murine myocardial infarction. The contrast agent relaxivity was decreased under in vivo conditions compared to in vitro measurements, which needs consideration when quantifying local contrast agent concentrations.

Dataset Information

In Vivo Quantification of Myocardial Infarction in Mice Using Micro-CT and a Novel Blood Pool Agent.

Publications

<i>In Vivo</i> Quantification of Myocardial Infarction in Mice Using Micro-CT and a Novel Blood Pool Agent.

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