This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.In a first phase of the project, we aim to establish and validate late enhancement CT imaging of subacute and chronic murine myocardial infarction (MI), which will be introduced by coronary ligation. This animal model has been used successfully for more then a decade in heart failure research, both in genetically modified mice and mice treated with novel heart failure therapies including stem cells.A major determinant of the degree of resulting heart failure is the infarct size. A careful, exact analysis of this cofounding factor is therefore mandatory for valid intervention studies (3). To date, noninvasive assessment of infarct size in mice is difficult. Some studies have described the use of late enhancement MRI to quantify myocardial infarction in mice. Late enhancement MRI technique has been established clinically, and has been validated carefully ('bright is dead'). Recently, a cardiac CT technique has been established in dogs and pigs with MI using iodixanol, based on the same pathophysiology as late enhancement MRI with Gd . Delayed hyperenhancement of the infarct is caused by a relatively higher volume of the extracellular space, due to the rarification of intact cardiac myocytes. The 4D cardiac micro-CT developed by the CIVM provides the opportunity to investigate delayed enhancement CT imaging in murine MI. This technique has the potential to noninvasively study infarct size in mice in a time- and cost-efficient manner.
Aim 1 : Establish and optimize a protocol with respect to contrast agent dosage and timing.
Aim 2 : Validate the established imaging protocol by comparison to the ex vivo gold standard for MI size quantification, TTC staining.
Aim 3 : Apply the validated imaging technique in a biologically cutting edge treatment study focussing on the modulation of infarct inflammation and healing through manipulation of monocyte recruitment.
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