Many diseases result in a heterogeneous distribution of regional function. This results in the need for a technique that can accurately measure deformation with high spatial resolution. We have developed computer aided speckle interferometry (CASI) to accomplish this task. Instead of tracking individual particles, CASI tracks clusters of particles. An isolated rabbit heart was arrested, and data was acquired in the perfused state, globally ischemic (15 min) state and reperfused state (10 min). CASI was used to determine the simultaneous deformation of over 1,000 points located in a region approximately 5.5 × 5.5 mm. A balloon was inserted into the left ventricle, and balloon pressure was increased from 5 to 20 mmHg. Ischemia and reperfusion resulted in a change in the epicardial deformation, leading to a change in principle strain from 2.8% to 4.5% (ischemia) to 2.8% (reperfused). A change in principle angle was also seen, with a 43° increase with 15 minutes of ischemia, and only a 10° change with reperfusion. In summary, we have a novel technique to measure regional deformation with high spatial resolution and found differences in the perfusion status of the heart.