Cancellous Bone Density Evaluation using Ultrasound Backscatter from an Imaging System: Exploring the Possibility for Fetal Bone Density Evaluation

Osteoporosis is a common chronic disease and a well known major source of morbility and mortality among the elderly. Low bone density also occurs in infants and small children during development and can be problematically excessive if the fetus experiences issues during pregnancy such as malnutrition, lack of vitamin D and smoking. Currently the only available methodologies for fetal bone density evaluation are Dual-energy X-ray Absorptiometry (DEXA) or Magnetic Resonance Imaging (MRI). Both are sensitive to movement artifacts. DEXA exposes the subjects to significant radiation so is not suggested during pregnancy. Quantitative MRI is noisy, expensive, slow (8-20 mins) and the effects of high field strengths on the developing fetus is unknown. Therefore, the goal of this study is to find a fast, accurate and non-ionizing method for the evaluation of fetal bone density. In this study, the quantitative ultrasound backscatter coefficient (BSC) was chosen to evaluate bone density using the B-mode ultrasound system. Compared with the speed of sound and ultrasound attenuation in the traditional ultrasound measurement for bone density, the backscatter method is more accessible to central sites such as the human spine and fetal femur bone. Additionally, it has a rapid path to commercialization with the potential to be added as a new feature in the current commercial ultrasound imaging systems for bone density evaluation. The contributions of this work are: 1. A simulation study was accomplished that compared backscatter coefficients from a single element transducer, a linear array transducer, and a curved array transducer with the change of trabecular thickness and trabecular spacing. An overall similar Pearson correlation (single: R = 0.94, SD = 10.84dB, linear: R = 0.92, SD = 6.6dB, curved: R=0.95, SD=6.89dB) between the BSC and porosity was found from three transducers, but the standard deviation (SD) was smaller from the two array probes. This improved standard deviation may result from the wider spatial range of the array transducers. 2. A simulation model using COMSOL for the fetal bone density evaluation was built based on the Biot’s poroelastic theory and the backscatter coefficient. The theoretical backscatter coefficient from the Biot model was calculated with the best available biomechanical parameters from the human femoral cancellous bone and the geometrical features of the fetal femur. This work also proposed a method for compensating the ultrasound signal attenuation from abdominal tissue, femur tissue, amniotic fluid between the probe and fetal femur. The result showed good correlation of BSC (R = -0.9970, P = 2.0058e^-04, SD = 10.21%) and apparent integrated backscatter (AIB) (R = -0.9469, P = 0.0146, SD = 10.62%) with the porosity. This suggests in vivo ultrasound bone evaluation could be implemented in the current commercial ultrasound B-mode systems. 3. An in vitro study was conducted that compared the backscatter coefficient (BSC), the apparent integrated backscatter (AIB) and the Spectrum Centroid Shift (SCS) from the fundamental backscatter signal and the second harmonics of the ultrasound imaging system. The result from the second harmonics (R : BSC = 0.7374, AIB = 0.6243, SCS =-0.6421) showed better correlation than the fundamental backscatter (R : BSC = 0.7055, AIB = 0.5393, SCS = -0.5858) with a gold standard bone mineral density obtained from DEXA scans of the same samples. An analysis from the Farran cylindrical model and the second harmonics of a rigid cylinder showed the second harmonics has less noise and showed better performance than the fundamental backscatter approach. In conclusion, the backscatter coefficient from ultrasound imaging showed good correlation in both the simulation studies and the in vitro study. It has the potential to be a convenient, fast, cheap methodology for adult and fetal bone density evaluation

Comparison of Conventional and Bayesian Analysis for the Ultrasonic Characterization of Cancellous Bone

This dissertation investigates the physics underlying the propagation of ultrasonic waves in cancellous bone. Although quantitative ultrasound has the potential to evaluate bone quality even better than the current gold standard X-ray based modality, its clinical utility has been hampered by the incomplete understanding of the mechanisms governing the interaction between ultrasound and bone. Therefore, studies that extend the understanding of the fundamental physics of the relationship between ultrasound and trabecular bone tissue may result in improved clinical capabilities. Ultrasonic measurements were carried out on excised human calcaneal specimens in order to study the effects of overlapping fast and slow compressional mode waves on the ultrasonic parameters of attenuation and velocity. Conventional analysis methods were applied to received sample signals that appeared to contain only a single wave mode. The same signals were also analyzed using a Bayesian parameter estimation technique that showed that the signals, which appeared to be only a single wave, could be separated into fast and slow wave components. Results demonstrated that analyzing the data under the assumption that only a single wave mode is present, instead of two interfering waves, yielded a phase velocity that lay between the fast and slow wave velocities and a broadband ultrasound attenuation that was much larger than the ultrasound attenuations of the individual fast and slow waves. The fast and slow wave ultrasonic parameters were found to correlate with microstructural parameters, including porosity, determined by microCT measurements. Simulations of fast and slow wave propagation in cancellous bone were carried out to demonstrate the plausibility of a proposed explanation for an anticipated sample-thickness dependence of the apparent attenuation in bovine bone. The results showed that an apparent sample-thickness dependence could arise if the fast and slow waves are not separated sufficiently and if frequency-domain analysis is not performed on broadband data. The sample-thickness dependence of the ultrasonic parameters was explored further using experimental data acquired on an equine cancellous bone specimen that was systematically shortened. The thickness of the sample varied the degree to which the fast and slow waves overlapped, permitting the use of conventional analysis methods for sufficiently long sample lengths. Bayesian parameter estimation was performed successfully on data from all sample lengths. The ultrasonic parameters obtained by both conventional and Bayesian analysis methods were found unexpectedly to display small, systematic variations with sample thickness. A very thorough and systematic series of studies were carried out on one-mode Lexan phantoms to investigate the potential cause of the observed sample-thickness dependence. These studies ruled out a series of potential contributors to the sample-thickness dependence, but yielded no clear cause. Although the clinical implications of the small but systematic sample-thickness dependence may be negligible, these studies may provide additional insights into the propagation of ultrasonic waves in cancellous bone and how to maximize the quality of information obtained

Ultra-high-speed imaging of bubbles interacting with cells and tissue

Ultrasound contrast microbubbles are exploited in molecular imaging, where bubbles are directed to target cells and where their high-scattering cross section to ultrasound allows for the detection of pathologies at a molecular level. In therapeutic applications vibrating bubbles close to cells may alter the permeability of cell membranes, and these systems are therefore highly interesting for drug and gene delivery applications using ultrasound. In a more extreme regime bubbles are driven through shock waves to sonoporate or kill cells through intense stresses or jets following inertial bubble collapse. Here, we elucidate some of the underlying mechanisms using the 25-Mfps camera Brandaris128, resolving the bubble dynamics and its interactions with cells. We quantify acoustic microstreaming around oscillating bubbles close to rigid walls and evaluate the shear stresses on nonadherent cells. In a study on the fluid dynamical interaction of cavitation bubbles with adherent cells, we find that the nonspherical collapse of bubbles is responsible for cell detachment. We also visualized the dynamics of vibrating microbubbles in contact with endothelial cells followed by fluorescent imaging of the transport of propidium iodide, used as a membrane integrity probe, into these cells showing a direct correlation between cell deformation and cell membrane permeability