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Elastometry Using Resonant Acoustics
Resonance phenomena are used in a wide range of applications such as the construction of bridges, electrical circuits, lasers, and even musical instruments. 35,000 years ago early humans were applying resonance phenomena to create bone flutes, and in 1940 resonance phenomena were responsible for the famous Tacoma Narrows bridge collapse. Much more recently, Dr. Oldenburg has developed a novel method of using these resonance phenomena to study the mechanical properties different biological materials. We call this Magnetomotive Resonant Acoustic Spectroscopy (MRAS) and use it to study how the mechanical properties of tissue are related to its functionality. With our system we are able to determine acoustical resonances of various biological samples and from these values we calculate their elasticity or Young's Modulus. Many biological processes such as disease, injury, age, etc. cause the elasticity of tissue to change. We use our system to detect the effects of disease on the elasticity of various types of tissue. We hope that eventually this will lead to diagnostic methods for early detection of life threatening ailments like cancer, cardiovascular diseases, and lung diseases. Several advantages of this resonance method compared to other diagnostic methods are its high accuracy and precision, high speed, and small sample volume.

Principle of Resonant Acoustic Spectroscopy

Figure 1. Principle of resonant acoustic spectroscopy using magnetic nanoparticles as "nanotransducers."

Blood Clot Elastometry
Every year almost 1 million people die of cardiovascular disease (CVD), which makes it the leading cause of death in the U.S. Myocardial infarction and strokes result from thrombosis, where excessive blood clots are formed and block blood flow, causing severe health problems. On the flip side, hemorrhagic disorders occur when the body cannot effectively form blood clots to stop bleeding after events such as injury or surgery. One aspect of blood clots that we can readily study with our optical coherence imaging system is their elasticity. The elasticity of a blood clot is closely related to its composition and structure. Understanding how it varies in different diseases may help in detecting and predicting the risk of thrombosis and hemorrhagic disorders.

To study the elasticity of blood clots we use Resonant Acoustic Spectroscopy (RAS) with optical vibrometry to measure the elastic modulus of clots. To do this we place a magnetic sheet on a clot sample and use and external magnetic field to generate a frequency-swept magnetic force on the sample. The resonance frequency of the clot is detected by monitoring the resulting displacement of the surface of the sample using optical coherence tomography. From this resonant frequency we can then compute the clot elastic modulus using our RAS method. Currently, we are studying the roles of fibrin and thrombin in blood clot formation and structure using this new technology.

Blood clot
Figure 2.

Human Airway Elastometry: A Study of Bronchiectasis
Bronchiectasis causes the breakdown of muscle and elastic tissue in lung airway tissue. This tissue destruction causes many health problems and can eventually lead to death. In a collaboration with the Cystic Fibrosis Center, we are studying bronchiectasis that occurs in the lungs of people with Cystic Fibrosis. One particularly harsh symptom of Cystic Fibrosis is severe lung infection. These infections cannot be cured by antibiotics and therefore cause severe scarring and damage to vital lung airways. We use our optical coherence tomography system along with our resonant acoustic spectroscopy technique to gain a better understanding of how bronchiectasis affects the mechanical properties of lung tissue. One way we study bronchiectasis involves growing human bronchial epithelial cells (the cells that make up our airways) on collagen/elastin scaffolds to create in vitro airway models. We attach a small magnet to these scaffolds and use an external magnetic field to stretch the scaffolds with varying forces. We can use OCT to monitor how much the scaffold stretches and from this information we can calculate the elasticity of the scaffolds. We can then add various biological substances to the scaffolds to mimic the bronchiectasis process and compare this data to the normal airway models to gain a better understanding of how bronchiectasis affects airways. We also use OCT and the RAS method to compare the elasticity of lung tissue of patients with cystic fibrosis to that of normal lung tissue. We do this by diffusing magnetic nanoparticles into small, cylindrically shaped pieces of airway. Then we use a frequency swept external magnetic field to find the resonant frequency (and therefore elasticity) of the tissue samples. Relating the structure and mechanical properties of lung tissue to the level of health and overall function of the lung is important in the study of bronchiectasis.

OCT of human airways
Figure 3. OCT images of inner surface of human lung airways. The CF airway has a corrugated structure due to bronchiectasis while the normal airway is smooth.


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