An elasticity microscope for high-resolution imaging of tissue stiffness using 50 MHz ultrasound.

Abstract

An elasticity microscope images tissue stiffness at fine resolution. Possible applications include dermatology, ophthalmology, pathology and tissue engineering. If the resolution approaches cellular dimensions, then this system may be useful in understanding tissue micromorphology. Elasticity images are reconstructed from displacement and strain fields measured throughout the specimen during controlled external loading. Methods are presented to utilize high frequency ultrasonic imaging for elasticity microscopy, by overcoming problems inherent in single element ultrasound to track coherent speckle motion during deformation. To test these methods, a 50 MHz elasticity microscope was constructed. This system was tested by imaging various tissue mimicking phantoms including: a homogeneous phantom, a phantom with several hundred micron thick layers of different stiffness, the cross-section of a hard cylindrical inclusion with known diameter of 265 $\mu$m, and hard spherical microcarrier beads (250 $\mu$m diameter) embedded in a soft gelatin phantom. Measurements from the homogeneous and cylindrical inclusion phantoms were compared to finite element simulations of internal deformation to verify experimental techniques. Measurements from multi-region phantoms were used to calculate the resolution of a normal axial strain image from the transition between regions (better than 90 $\mu$m axial spatial resolution). Tissue engineering is one of many areas that can benefit from high resolution elasticity imaging. The resolution of the current experimental system is sufficient to detect different tissue layers, caused by cell growth and matrix development. Results from the layered phantom are compared to experimental results from tissue engineered smooth muscle, grown from cultured cells and synthetic matrices. Typically, cell growth on the interior region of the scaffolding or matrix is limited by nutrient delivery, resulting in a layered structure difficult to image with standard ultrasound techniques. Elasticity micrographs clearly differentiate viable cell layers from synthetic matrix and necrotic cells. Histological differences are confirmed between tissue engineered smooth muscle grown on biodegradable matrix and a cultured matrix without seeded cells. These experiments exemplify the potential of high frequency ultrasound for elasticity microscopy. This research should serve as a cornerstone, allowing others to see the advantages of high resolution elasticity imaging and apply it to their particular needs.