On average, 274 people die every day from blood clots — one person every six minutes. Each year, 100,000 to 300,000 deaths occur from blood clots, such as deep vein thrombosis. This is greater than the total number of people who lose their lives each year to AIDS, breast cancer and motor vehicle crashes combined.

Diagnosing a blood clot after physical examination may include ultrasounds, angiographies, computed tomography scans and X-rays, all depending on the suspected location of the clot. But what if there were an even better way to evaluate blood clots?

Both light and electron microscopy imaging now allow unprecedented views of clotting, especially in animal models of hemostasis and thrombosis. But understanding three-dimensional high-resolution clot structure remains incomplete because of optical impenetrability of clots beyond a few cell layers in depth.

However, John W. Weisel of the University of Pennsylvania School of Medicine and a collaborative group from Weisel's lab and the labs of Mark Alber of the University of California, Riverside, and Jeremiah Zartman of the University of Notre Dame recently reported on how to use powerful optical microscopy techniques to study the 3-D structure of dangerous clots for the first time.

While it has been shown that erythrocytes are compressed to form polyhedrocytes during clot contraction, observations of this phenomenon have been impeded by the inability to easily image inside clots. This efficient and nondestructive method, called cCLOT, is removes the heme and makes the whole clot clear without changing its 3-D structure. In addition, cCLOT optical clearing has the potential to facilitate imaging of ex vivo clots and thrombi derived from healthy or pathological conditions.

According to Weisel, by analyzing the clot structure from patients, a more detailed understanding of various clot structures could reveal why pieces of certain clots break off and lead to deadly complications. The research group found that during contraction, the red blood cells change from their normal bioconcave shape to olyhedral and are tightly packed without changing in volume.

What's on the horizon? If researchers can identify ways to achieve faster optical clearing and image analysis, they could — with such high-throughput approaches — examine the effects of different drugs on the clotting process or clot contraction.

The ultrastructural signatures that might be identified in 3-D specimens are still unknown, but there is promise that this optical clearing method will help in studying different types of 3-D structures with the hope of obtaining new or different information than current diagnostic techniques, as well as a better understanding of heart attacks and strokes.