Dec. 7, 2009 MIT scientists including Elazer R. Edelman, the Thomas D. and Virginia W. Cabot Professor of Health Science and Technology (HST), and HST postdoctoral associate Vijaya B. Kolachalama, developed computer models to predict physiologically realistic drug delivery patterns from stents in branched arterial vessels. They simulated several arterial settings to show that drug distribution in these situations is determined by a complex calculation of the stent's position relative to arterial branches and constant blood flow changes caused by the branching.
"We now demonstrate for the first time that spatial variation in drug distribution can be significant when appreciated from a three-dimensional perspective and this viewpoint can only be gained with the use of these model systems," said Edelman.
Drug-eluting stents are now widely used all over the world to treat obstructive arterial disease, yet some patients with the stents have suffered life-threatening side effects: an increase risk of blood clotting and heart attacks. Several important questions remain unanswered -- in particular, the mechanisms that govern drug delivery to specific lesion sites are poorly defined and pose challenges for stent designers, physicians, and regulatory agencies that must evaluate stents' safety and efficacy.
Predicting drug distribution is complicated by the branching of arteries into two or more vessels, which establishes alterations in flow, wall shear stress and geometries. All of those can be modeled and defined mathematically, however, the variations cannot be captured across the full spectrum of perturbations and combinations in animal systems or in the lab, let alone the human. Computational models are therefore required.
"By observing the arterial drug distribution patterns for various settings, we understood that drug released from the stent does not reach uniformly to all regions of the vessel and this non-uniformity depends on where the stent is placed in the artery as well as the blood flow that is entering the vessel," says Edelman. "Appreciating this phenomenon for more complex cases like branched vessels is non-intuitive, but now we have a computer model that gave us the much needed insight."
"Modeling stent-based drug delivery in branched vessels is critically important because these are frequent sites of arterial disease and yet there are no dedicated devices that are FDA-approved or efficient strategies using multiple stents to specifically treat these locations," says Kolachalama. "Our computer model shows that for some arterial settings, a single stent in the main-branch of the fork can provide drug to the side-branch. This observation could be important to consider, especially when one has to place stents in both branches."
How they did it: The computer model was generated by combining principles of digital image processing and parametric computer-aided geometry design with computational fluid dynamics and mass transport. A video link showing how these geometry models are created can be found on the journal website. The authors believe this modeling technique can be extended to simulate several settings with various stent designs as well as complex arterial geometries with and without disease, altered flow environments and other boundary conditions.
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- Vijaya Kolachalama, Evan Levine, Elazer Edelman. Luminal Flow Amplifies Stent-Based Drug Deposition in Arterial Bifurcations. PLoS ONE, 2009; 4 (12): e8105 DOI: 10.1371/journal.pone.0008105
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