Applying High-Frequency Ultrasound to Examine Structures and Physical Properties of Cells and Tissues

Medical ultrasound is a diagnostic imaging technique used for visualizing subcutaneous body structures. The frequencies used in conventional diagnostic ultrasound are typically 2–10 MHz. For scanning acoustic microscopy (SAM), the frequencies applied to image cells and tissues are >50 MHz. Increasing the frequency increases spatial resolution, but reduces the depth that can be imaged. The advantages of using SAM over conventional light and electron microscopes include imaging specimens without requiring any preparations which may kill or alter them; this provides a more accurate representation of them. SAM’s main components are similar to those found on typical light microscopes, but the lens is often replaced by a confocal transducer. The ultrasound signal encountering the specimen generally has three results: scatter, transmission, or reflection; these signals are then merged to form the image as either a B-Scan or C-Scan. The acoustic parameters determining the image quality are absorption and scattering. SAM can objectively quantify the surface characteristics of the specimen being scanned and can also study the elastic properties of cells and tissues to discern differences between healthy and affected conditions. SAM has the potential as a major instrument of detection and analyses in biomedical research and clinical studies

Characterizing Morphology and Nonlinear Elastic Properties of Normal and Thermally Stressed Engineered Oral Mucosal Tissues Using Scanning Acoustic Microscopy

This study examines the use of high-resolution ultrasound to monitor changes in the morphology and nonlinear elastic properties of engineered oral mucosal tissues under normal and thermally stressed culture conditions. Nonlinear elastic properties were determined by first developing strain maps from acoustic ultrasound, followed by fitting of nonlinear stress?strain data to a 1-term Ogden model. Testing examined a clinically developed ex vivo produced oral mucosa equivalent (EVPOME). As seeded cells proliferate on an EVPOME surface, they produce a keratinized protective upper layer that fills in and smoothens out surface irregularities. These transformations can also alter the nonlinear stress/strain parameters as EVPOME cells differentiate. This EVPOME behavior is similar to those of natural oral mucosal tissues and in contrast to an unseeded scaffold. If ultrasonic monitoring could be developed, then tissue cultivation could be adjusted in-process to account for biological variations in their development of the stratified cellular layer. In addition to ultrasonic testing, an in-house-built compression system capable of accurate measurements on small (?1.0?1.5?cm2) tissue samples is presented. Results showed a near 2.5-fold difference in the stiffness properties between the unstressed EVPOME and the noncell-seeded acellular scaffold (AlloDerm?). There were also 4?greater differences in root mean square values of the thickness in the unseeded AlloDerm compared to the mature unstressed EVPOME; this is a strong indicator for quantifying surface roughness.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/140241/1/ten.tec.2012.0467.pd

Use of Scanning Acoutic Microscopy to Examine and Evaluate Physical Characteristics of Mucosal Tissues.

Elastic properties of mucosal tissues (namely within the oral cavity and the uterine lining) are poorly understood. Deformation, flow, and remodeling are fundamental to a variety of higher cell functions including cell contraction, adhesion, spreading, wound healing, and division, and have been implicated as well in mechanotransduction, regulation of protein and DNA synthesis, and programmed cell death. Our understanding of the physical elastic measurements are unclear, both for natural and synthetically engineered soft tissues. The characteristics of tissue engineered oral mucosal tissues have resulted in successful transplantation. These oral mucosal tissues have also been incorporated into vaginoplasty. The versatility of the oral mucosal tissues shows the potential to incorporate as a surrogate for other soft tissues to repair/replace damaged or missing tissues and organs. Of critical importance is whether engineered tissues, specifically a commercially available acellular cadaveric dermal tissue (AlloDerm®) and an ex vivo produced oral mucosal equivalent (EVPOME) match the mechanical properties of native tissues. If the oral tissues’ structural and physical functions are similar, it is possible that they are compatible for surgical implantation to replace/repair damaged or missing uterine and vaginal tissues. Scanning acoustic microscopy (SAM) has been shown to effectively image the surface characteristics and mechanical properties of tissues at the micrometer range. We used SAM to study morphologies and elastic properties of both natural and engineered tissues; the latter being the AlloDerm® and EVPOME. These studies include using SAM to measure and characterize whether AlloDerm’s® and/or EVPOME’s physical properties are similar to natural oral mucosal tissues; this is a significant step to determine whether such tissues are transplantable to other areas of the body. Further studies to characterize regulated changes in the EVPOME involved using both SAM and standard histology images to analyze the EVPOME after it underwent an elevated thermal stress test. Finally, using a compression mechanism in conjunction with SAM - a known method to test for elasticity in tissues – this study aims to determine the elastic properties of soft tissues: oral mucosa and skin. In addition, the same tests were performed on AlloDerm® and EVPOME to compare their elastic properties.Ph.D.Biomedical EngineeringUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/84638/1/fwinterr_2.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/84638/2/fwinterr_1.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/84638/3/fwinterr_3.pd