Medical Imaging 2011: Physics of Medical Imaging, 2011
Ultrasound elastography tracks tissue displacements under small levels of compression to obtain i... more Ultrasound elastography tracks tissue displacements under small levels of compression to obtain images of strain, a mechanical property useful in the detection and characterization of pathology. Due to the nature of ultrasound beamforming, only tissue displacements in the ...
Poroelastic tissue strain imaging measures the time-varying and spatially varying deformation of ... more Poroelastic tissue strain imaging measures the time-varying and spatially varying deformation of a soft-tissue matrix during compression as the tissue fluid flows out of the compartmental boundaries. With the help of ultrasound, it has been carried out by observing the evolution of the images of the ultrasound echo strain over time, which shows that, in a stress-relaxation experiment (constantly applied global axial strain), a front of negative dilatation (volumetric strain) propagates slowly from the boundaries of a sample toward the center of the compressed region. The fitting of equations that predict this behavior to experimental data has earlier allowed quantitative imaging of the product of aggregate modulus and permeability of a tissue phantom, HAk, and its Poisson's ratio, ν. An ability to image and measure such novel tissue characteristics is likely to benefit biomedical research and have a wide range of clinical applications, including the assessment of lymphoedema, th...
2019 IEEE International Ultrasonics Symposium (IUS)
Acoustic cluster therapy (ACT) is designed to overcome some of the limitations of conventional mi... more Acoustic cluster therapy (ACT) is designed to overcome some of the limitations of conventional microbubbles for ultrasound-assisted delivery of drugs to tumors. ACT consists of clusters of oil microdroplets and microbubbles. Diagnostic ultrasound imaging can be used to visualize the microbubble component and to activate (vaporize) the droplets to produce large (>20 μm) bubbles which lodge in the tumor’s microvessels. A subsequent low-frequency ultrasound field then gently pulsates the activated bubbles which are in direct contact with endothelium, enhancing vascular permeability. We present in-vivo pre-clinical imaging experiments designed to better understand ACT behavior. Conventional microbubbles were observed to wash out of tumors within 6 min whereas activated ACT failed to wash out during the observation time of 15 min, confirming activation. Stationary echoes in tumors uniquely accumulated in fundamental B-mode images after ACT activation (but not with a microbubble agent, nor in nonlinear contrast mode) providing a signature for identifying ACT activation in vivo. ACT significantly enhanced CW800 dye uptake in tumor relative to dye alone. Photoacoustic CW800 signals appeared in the tumor periphery, suggesting potential for high-resolution, three-dimensional dynamic monitoring although with lower sensitivity than fluorescence imaging.
2020 IEEE International Ultrasonics Symposium (IUS), 2020
Parametric imaging is a tool to visualize the parameters extracted from dynamic contrast enhanced... more Parametric imaging is a tool to visualize the parameters extracted from dynamic contrast enhanced ultrasound (DCE-US) and the corresponding time amplitude curves (TAC) to illustrate the heterogeneity of those parameters across a tumour. TAC generated using DCE-US can be influenced by imaging mode, plane wave (PWI) or focussed imaging (FI) and the parameter choices. This has been previously studied for a single vessel phantom and a micro vasculature phantom when laterally located clutter from grating lobes was observed for PWI. Here we study the effect of such clutter on parametric imaging for three TAC metrics: peak intensity (PI), time from injection to peak (TIP) and mean transit time (MTT), using a microvascular flow phantom. DCE-US images were obtained using a Vantage (Verasonics Inc.) and a pulse-inversion algorithm. 800 frames were recorded at 10 Hz for PWI and FI. All measurements were repeated 3 times, injecting 0.4 ml of contrast agent (Sonozoid). The concept of TAC coherence, the similarity of the TACs between any two locations in the field of view, was introduced and used as a measure of TAC information leakage, a blurring of the ability to see spatial variation in TAC shape. Such leakage may be due, for example, to a broad beam (high side lobes) or strong grating lobes. A greater signal leakage was observed for PWI which raises concerns over the use of PWI DCE- US when it is important to maintain sensitivity to vascular heterogeneity in tumours, especially when interested in response to treatment.
2016 IEEE International Ultrasonics Symposium (IUS), 2016
Optoacoustic imaging has demonstrated potential for imaging tumour micovasculature and hypoxia bu... more Optoacoustic imaging has demonstrated potential for imaging tumour micovasculature and hypoxia but provides limited information on haemodynamics. Conversely, dynamic contrast enhanced ultrasound (DCE-US) is widely used to evaluate perfusion. This study describes a novel method of co-registering optoacoustic tomography images with DCE-US images to demonstrate, in preclinical cancer models, the value of combining the two imaging modalities. Imaging results showed the importance of the combinative imaging approach for interpreting optoacoustic images, demonstrating that not all regions which lack an optoacoustic blood-signal are entirely avascular; some are just poorly perfused. Furthermore, significant differences of potential biological importance were observed between the microbubble time intensity curve parameters of image regions that lacked, versus those which possessed, an optoacoustic blood-signal.
Intense pulsed light (IPL) is a high-intensity treatment for skin disorders and ageing. As this t... more Intense pulsed light (IPL) is a high-intensity treatment for skin disorders and ageing. As this treatment regime is often poorly regulated and inadequately studied, we investigate IPL as a cosmetic device and its effects on dermal collagen components of the skin. Biopsies from the back-neck folds of a 4-week-old, 25 kg large white pig were irradiated with intense pulsed light (IPL) (l= 584 nm) at an increased radiation dose of 40 J/cm2 once, thrice and ten times. Samples were cryo-sectioned (10 μm) and stained with picro sirrus red. Ex-vivo biopsies were assessed with polarized light microscopy (PLM), atomic force microscopy (AFM) and scanning acoustic microscopy. Customized software was used to map the sound speed and attenuation on the ultrasonic images Differences in collagen structure were observed between all three levels of irradiation progressing depth-wise into the epidermis. Ex-vivo porcine tissue demonstrated loss of D-banding and gelatinization with increasing dermal dept...
Dynamic contrast enhanced ultrasound (DCE-US) imaging has the potential to provide quantitative i... more Dynamic contrast enhanced ultrasound (DCE-US) imaging has the potential to provide quantitative information which is sensitive to tumour perfusion, an indicator for tumour response to radiotherapy. To increase the reproducibility of time-intensity curve (TIC) characteristics, we are developing a 3 $D$ DCE-US imaging system. There are, however, many choices to be made in system design, such as whether to use plane wave (PWI) or focused imaging (FI), and the values to use for parameters such as focal depth (FD), F-number (F#), mechanical index (MI) and number of angles (NA) (for PWI). We evaluated the effect of such choices on TICs (we refer to time-amplitude curve (TAC) here), using a microvascular flow phantom containing $\sim 100, 000$ parallel microtubes, each $200\mu \text{m}$ in diameter. DCE-US 2D images were obtained using a Vantage (Verasonics Inc.) and a pulse-inversion algorithm. 800 frames were recorded at 10 Hz for PWI and FI. All measurements were repeated 3 times, injec...
Increased stiffness in the extracellular matrix (ECM) contributes to tumor progression and metast... more Increased stiffness in the extracellular matrix (ECM) contributes to tumor progression and metastasis. Therefore, stromal modulating therapies and accompanying biomarkers are being developed to target ECM stiffness. Magnetic resonance (MR) elastography can noninvasively and quantitatively map the viscoelastic properties of tumors in vivo and thus has clear clinical applications. Herein, we used MR elastography, coupled with computational histopathology, to interrogate the contribution of collagen to the tumor biomechanical phenotype and to evaluate its sensitivity to collagenase-induced stromal modulation. Elasticity (Gd) and viscosity (Gl) were significantly greater for orthotopic BT-474 (Gd = 5.9 ± 0.2 kPa, Gl = 4.7 ± 0.2 kPa, n = 7) and luc-MDA-MB-231-LM2-4 (Gd = 7.9 ± 0.4 kPa, Gl = 6.0 ± 0.2 kPa, n = 6) breast cancer xenografts, and luc-PANC1 (Gd = 6.9 ± 0.3 kPa, Gl = 6.2 ± 0.2 kPa, n = 7) pancreatic cancer xenografts, compared with tumors associated with the nervous system, inc...
Medical Imaging 2011: Physics of Medical Imaging, 2011
Ultrasound elastography tracks tissue displacements under small levels of compression to obtain i... more Ultrasound elastography tracks tissue displacements under small levels of compression to obtain images of strain, a mechanical property useful in the detection and characterization of pathology. Due to the nature of ultrasound beamforming, only tissue displacements in the ...
Poroelastic tissue strain imaging measures the time-varying and spatially varying deformation of ... more Poroelastic tissue strain imaging measures the time-varying and spatially varying deformation of a soft-tissue matrix during compression as the tissue fluid flows out of the compartmental boundaries. With the help of ultrasound, it has been carried out by observing the evolution of the images of the ultrasound echo strain over time, which shows that, in a stress-relaxation experiment (constantly applied global axial strain), a front of negative dilatation (volumetric strain) propagates slowly from the boundaries of a sample toward the center of the compressed region. The fitting of equations that predict this behavior to experimental data has earlier allowed quantitative imaging of the product of aggregate modulus and permeability of a tissue phantom, HAk, and its Poisson's ratio, ν. An ability to image and measure such novel tissue characteristics is likely to benefit biomedical research and have a wide range of clinical applications, including the assessment of lymphoedema, th...
2019 IEEE International Ultrasonics Symposium (IUS)
Acoustic cluster therapy (ACT) is designed to overcome some of the limitations of conventional mi... more Acoustic cluster therapy (ACT) is designed to overcome some of the limitations of conventional microbubbles for ultrasound-assisted delivery of drugs to tumors. ACT consists of clusters of oil microdroplets and microbubbles. Diagnostic ultrasound imaging can be used to visualize the microbubble component and to activate (vaporize) the droplets to produce large (>20 μm) bubbles which lodge in the tumor’s microvessels. A subsequent low-frequency ultrasound field then gently pulsates the activated bubbles which are in direct contact with endothelium, enhancing vascular permeability. We present in-vivo pre-clinical imaging experiments designed to better understand ACT behavior. Conventional microbubbles were observed to wash out of tumors within 6 min whereas activated ACT failed to wash out during the observation time of 15 min, confirming activation. Stationary echoes in tumors uniquely accumulated in fundamental B-mode images after ACT activation (but not with a microbubble agent, nor in nonlinear contrast mode) providing a signature for identifying ACT activation in vivo. ACT significantly enhanced CW800 dye uptake in tumor relative to dye alone. Photoacoustic CW800 signals appeared in the tumor periphery, suggesting potential for high-resolution, three-dimensional dynamic monitoring although with lower sensitivity than fluorescence imaging.
2020 IEEE International Ultrasonics Symposium (IUS), 2020
Parametric imaging is a tool to visualize the parameters extracted from dynamic contrast enhanced... more Parametric imaging is a tool to visualize the parameters extracted from dynamic contrast enhanced ultrasound (DCE-US) and the corresponding time amplitude curves (TAC) to illustrate the heterogeneity of those parameters across a tumour. TAC generated using DCE-US can be influenced by imaging mode, plane wave (PWI) or focussed imaging (FI) and the parameter choices. This has been previously studied for a single vessel phantom and a micro vasculature phantom when laterally located clutter from grating lobes was observed for PWI. Here we study the effect of such clutter on parametric imaging for three TAC metrics: peak intensity (PI), time from injection to peak (TIP) and mean transit time (MTT), using a microvascular flow phantom. DCE-US images were obtained using a Vantage (Verasonics Inc.) and a pulse-inversion algorithm. 800 frames were recorded at 10 Hz for PWI and FI. All measurements were repeated 3 times, injecting 0.4 ml of contrast agent (Sonozoid). The concept of TAC coherence, the similarity of the TACs between any two locations in the field of view, was introduced and used as a measure of TAC information leakage, a blurring of the ability to see spatial variation in TAC shape. Such leakage may be due, for example, to a broad beam (high side lobes) or strong grating lobes. A greater signal leakage was observed for PWI which raises concerns over the use of PWI DCE- US when it is important to maintain sensitivity to vascular heterogeneity in tumours, especially when interested in response to treatment.
2016 IEEE International Ultrasonics Symposium (IUS), 2016
Optoacoustic imaging has demonstrated potential for imaging tumour micovasculature and hypoxia bu... more Optoacoustic imaging has demonstrated potential for imaging tumour micovasculature and hypoxia but provides limited information on haemodynamics. Conversely, dynamic contrast enhanced ultrasound (DCE-US) is widely used to evaluate perfusion. This study describes a novel method of co-registering optoacoustic tomography images with DCE-US images to demonstrate, in preclinical cancer models, the value of combining the two imaging modalities. Imaging results showed the importance of the combinative imaging approach for interpreting optoacoustic images, demonstrating that not all regions which lack an optoacoustic blood-signal are entirely avascular; some are just poorly perfused. Furthermore, significant differences of potential biological importance were observed between the microbubble time intensity curve parameters of image regions that lacked, versus those which possessed, an optoacoustic blood-signal.
Intense pulsed light (IPL) is a high-intensity treatment for skin disorders and ageing. As this t... more Intense pulsed light (IPL) is a high-intensity treatment for skin disorders and ageing. As this treatment regime is often poorly regulated and inadequately studied, we investigate IPL as a cosmetic device and its effects on dermal collagen components of the skin. Biopsies from the back-neck folds of a 4-week-old, 25 kg large white pig were irradiated with intense pulsed light (IPL) (l= 584 nm) at an increased radiation dose of 40 J/cm2 once, thrice and ten times. Samples were cryo-sectioned (10 μm) and stained with picro sirrus red. Ex-vivo biopsies were assessed with polarized light microscopy (PLM), atomic force microscopy (AFM) and scanning acoustic microscopy. Customized software was used to map the sound speed and attenuation on the ultrasonic images Differences in collagen structure were observed between all three levels of irradiation progressing depth-wise into the epidermis. Ex-vivo porcine tissue demonstrated loss of D-banding and gelatinization with increasing dermal dept...
Dynamic contrast enhanced ultrasound (DCE-US) imaging has the potential to provide quantitative i... more Dynamic contrast enhanced ultrasound (DCE-US) imaging has the potential to provide quantitative information which is sensitive to tumour perfusion, an indicator for tumour response to radiotherapy. To increase the reproducibility of time-intensity curve (TIC) characteristics, we are developing a 3 $D$ DCE-US imaging system. There are, however, many choices to be made in system design, such as whether to use plane wave (PWI) or focused imaging (FI), and the values to use for parameters such as focal depth (FD), F-number (F#), mechanical index (MI) and number of angles (NA) (for PWI). We evaluated the effect of such choices on TICs (we refer to time-amplitude curve (TAC) here), using a microvascular flow phantom containing $\sim 100, 000$ parallel microtubes, each $200\mu \text{m}$ in diameter. DCE-US 2D images were obtained using a Vantage (Verasonics Inc.) and a pulse-inversion algorithm. 800 frames were recorded at 10 Hz for PWI and FI. All measurements were repeated 3 times, injec...
Increased stiffness in the extracellular matrix (ECM) contributes to tumor progression and metast... more Increased stiffness in the extracellular matrix (ECM) contributes to tumor progression and metastasis. Therefore, stromal modulating therapies and accompanying biomarkers are being developed to target ECM stiffness. Magnetic resonance (MR) elastography can noninvasively and quantitatively map the viscoelastic properties of tumors in vivo and thus has clear clinical applications. Herein, we used MR elastography, coupled with computational histopathology, to interrogate the contribution of collagen to the tumor biomechanical phenotype and to evaluate its sensitivity to collagenase-induced stromal modulation. Elasticity (Gd) and viscosity (Gl) were significantly greater for orthotopic BT-474 (Gd = 5.9 ± 0.2 kPa, Gl = 4.7 ± 0.2 kPa, n = 7) and luc-MDA-MB-231-LM2-4 (Gd = 7.9 ± 0.4 kPa, Gl = 6.0 ± 0.2 kPa, n = 6) breast cancer xenografts, and luc-PANC1 (Gd = 6.9 ± 0.3 kPa, Gl = 6.2 ± 0.2 kPa, n = 7) pancreatic cancer xenografts, compared with tumors associated with the nervous system, inc...
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