Acute-infarct selective cardiac MRI contrast agent

Ruzsics, Balazs

Abstract

Reliable diagnostic differentiation between acute and chronic myocardial infarcts would be of great benefit for cardiac surgeons and interventional cardiologists. Such differentiation could be used to make decisions about which vessels and in what order would be reopened or bypassed. MRI is an intrinsically noninvasive diagnostic tool and the Delayed Enhancement MRI technique is capable of highlighting infarct by the accumulation of contrast agents (e.g., MagnevistZ) into it, causing MRI intensity hyperenhancement in infarcted myocardial tissue. Unfortunately, however, the technique, with the presently available contrast agents, does not differentiate between acute, i.e., relatively fresh, infarcts and chronic, i.e., old infarcts. A recently proffered addition to this technique, the use of T2-weighted images taken before the administration of the contrast agent, does sometimes distinguish acute infarcts from chronic infarcts but due to various factors it does not do so in a predictable manner. This unpredictability essentially prevents the use of this technique in clinical decision making. Based on our preliminary data, we offer the use of a new myocardial contrast agent, Gadolinium-ABE-DTTA, which selectively highlights acute infarcts by causing signal hyperenhancement, yet does not cause hyperenhancement in infarcts that are beyond 2 weeks old. MRI imaging, using this agent, would allow the sought-after differentiation of acute from chronic infarct in a highly reliable manner. Our long term objective, using a canine model of myocardial infarction, is to prove the practical ability to exercise """"""""vessel triage"""""""", to characterize the parameters for its application, and to investigate the tissue mechanism of the differentiation. Among the parameters the optimal dose, the earliest post-infarct time of the emergence of signal hyperenhancement, and the time window (earliest and latest time) of the effect will be determined. As a first step, in this Phase I project a limited objective will be achieved, to prove with sufficient statistical significance the ability of this agent to show differentiation between early acute (less than 2 days old) and late acute (more than 8 days old) infarcts. A Phase II application will be submitted once this limited objective is met. Following Phase II, which will pursue the long term objective described above, steps will be taken towards commercialization. ? ? ?