Abstract

High frequency ultrasound has been shown to detect structural and physical changes in cell ensembles during apoptosis and hence has the potential of monitoring cancer treatment. Ultrasound contrast agents have also been shown to enhance contrast between blood and the surrounding tissue and hence may be used to distinguish between treated and untreated tumours. Theoretical models of high frequency ultrasound scattering from individual cells and ultrasound contrast agents (UCAs) are needed in order to develop methods for using high frequency ultrasound to classify tumours, quantify their responses to treatment, and eventually provide a better cancer detection and treatment monitoring techniques. This work introduces a new technique for measuring the ultrasound backscatter from individual micron-sized objects by combining a microinjection system with a co-registered optical microscope and an ultrasound imaging device. The system was calibrated by measuring the backscatter response from polystyrene microspheres and comparing it to theoretical predictions of an elastic sphere. The backscatter responses from single sea urchin oocytes and acute myloid leukemia cells were also investigated. It was found that such responses are best modelled using the fluid sphere model. A finite element model was also introduced to study scattering from microspheres and UCAs. The Helmholtz equation was used to describe the propagation of sound waves in the fluid domains whereas the constitutive equation was used to describe the stress-strain relationship in the solid domains. Studies on polystyrene microspheres and UCAs revealed the existence of a systematic relationship between the resonance frequencies and the microsphere surface modes. No such a relationship was found for the UCAs of interest. Instead, these agents exhibited a collection of complex oscillations which appear to be a combination of various surface modes. Increasing the UCA's shell thickness and its shear modulus produced a shift in the resonance frequencies to higher values. A decrease in UCA diameter produced similar effects. The importance of these findings towards the understanding of the UCA behaviour at high frequencies and the generation of harmonics are discussed. Future work includes the measurement of the backscatter response from individual UCAs and cells at various apoptotic stages.

Highlights

  • Cancer is a malignant tumour of potentially unlimited growth and is the leading cause of early death in Canada, being responsible for almost 29.5% of all deaths according to a report published by StatsCan in 2004 (StatsCan, 2004)

  • This is possibly due to the presence of foreign objects in the suspension, as no concurrent microscopy of the scattering objects was available, which may have led to the erroneous interpretation of the measured backscattered pulses. These findings presented in this work lead to the conclusion that individual OCI-Acute Myloid Leukemia (AML)-5 cells may be modeled as fluid sphere, to PC-3 prostate carcinoma cells (Baddour et al, 2007) and sea urchin oocytes (Falou et al, 2008) when these cells are suspended in solution

  • The developed technique was shown to be successful in measuring the ultrasonic backscatter responses from individual micron-size objects at high frequencies

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Summary

Introduction

Cancer is a malignant tumour of potentially unlimited growth and is the leading cause of early death in Canada, being responsible for almost 29.5% of all deaths according to a report published by StatsCan in 2004 (StatsCan, 2004). Theoretical models of ultrasound scattering at the cellular level are needed in order to develop methods for using ultrasound backscatter measurements to classify tumours or determine their response to treatment. The development of these models requires an understanding of the mechanical properties of components of a cell such as the nucleus and the cytoplasm. The measurement of the ultrasound backscatter from individual micron-sized objects such as cells is needed for applications ranging from tissue characterization to molecular imaging This has been previously done by scanning a sample with objects in suspension and analyzing the brightest signals received, assuming these to be caused by scattering events from the single objects of interest (Baddour et al, 2005; Baddour et al, 2007; Falou et al, 2008). Refer to Appendix A for a detailed description of the Church model

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