Jeffrey Bamber | The Institute of Cancer Research (original) (raw)

Papers by Jeffrey Bamber

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 ...

Ultrasound in Medicine & Biology, 2011

This paper presents a new method for acquiring 3D volumes of ultrasonic axial strain data. The me... more This paper presents a new method for acquiring 3D volumes of ultrasonic axial strain data. The method uses a mechanically-swept probe to sweep out a single volume while applying a continuously varying axial compression. We examine the image quality and ease of use of the new method with in vitro and in vivo experiments. The new method is easier to use than the current best alternative and so more reliably produces images of superior quality.

Frontiers in Physics, 2021

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...

2017 IEEE International Ultrasonics Symposium (IUS), 2017

2019 IEEE International Ultrasonics Symposium (IUS), 2019

Contrast-enhanced photoacoustic imaging has shown a great potential in various medical imaging ap... more Contrast-enhanced photoacoustic imaging has shown a great potential in various medical imaging applications. Although different types of customized contrast agents were developed over the decade, there is no commercial FDA-approved photoacoustic imaging contrast agents. This study shows the in vivo photoacoustic imaging of low-boiling-point phase-change nanodroplets, made using ingredients from an existing commercial microbubble ultrasound contrast agents without any dye coated, in a mouse to demonstrate that commercial ultrasound contrast agents may have the potential to be used to facilitate the clinical translation of photoacoustic imaging. Decafluorobutane-core lipid-shell nanodroplets were manufactured. The homemade decafluorobutane droplet solution has the same core composition as the commercial MicroMarker© (FUJIFILM, Visualsonics) and Sonazoid© (GE Healthcare) contrast microbubbles. The results show that, after activation, signals from the spleen region have been significantly enhanced. As the droplets do not have any dye coating on the surface, one potential reason for the photo-activation of the droplets could be that the blood cells nearby absorb energy from the light. As the ingredients of the droplets are the same as some existing commercial microbubble contrast agents, this study demonstrates that droplets made from condensed commercial bubbles may have the potential to be used to facilitate the clinical translation of contrast-enhanced photoacoustic imaging.

Frontiers in Pharmacology, 2020

agent and that ultrasound contrast enhancement during or before ACT treatment may be employed as ... more agent and that ultrasound contrast enhancement during or before ACT treatment may be employed as a biomarker of therapeutic response during clinical use.

Cochrane Database of Systematic Reviews, 2018

How up-to-date is this review? The review authors searched for and used studies published up to A... more How up-to-date is this review? The review authors searched for and used studies published up to August 2016. *In these studies biopsy was the reference standard (means of establishing the final diagnosis). High-frequency ultrasound for diagnosing skin cancer in adults (Review)

AccessScience

A photoacoustic (PA) spectroscopy system has been built to study the differences between the PA s... more A photoacoustic (PA) spectroscopy system has been built to study the differences between the PA spectra of oxygenated and deoxygenated blood, and various PA contrast agents, with a view to optimising the identification of these media in clinical PA images. A variable-wavelength laser delivers short (ns) pulses of light, via a fibre optic cable, into a sample held between 75 µm transparent membranes. The optical wavelength is controlled by a computer, which scans the wavelength range 400-700 nm using a different pulse for each wavelength. Each pulse causes the sample to momentarily expand and emit a pressure wave, the energy of which is measured by the computer using a digital oscilloscope that samples the signal from a strongly focused 7.5 MHz ultrasound transducer. The resulting optical spectra are corrected for some system variables, such as the wavelengthdependent laser energy. Further corrections are planned, so that the measurement is truly of optical absorption coefficient at each wavelength. Even without these additional corrections however, the measured PA spectrum of oxygenated blood strongly resembles the published optical absorption spectrum. These results suggest that, in addition to its intended use for determining the optimum wavelengths for clinical PA imaging of blood oxygenation level and contrast agent concentration, this system may have applications as a laboratory spectrophotometer. Unlike traditional transmission spectrophotometers, which measure the extinction coefficient, the PA spectrometer will measure the absorption coefficient. This will make it suitable for use with (a) optically dark samples such as normal blood, which cannot be analysed in a standard spectrophotometer without dilution, and (b) turbid media, which normally require an optical scattercorrection to convert the extinction coefficient to an absorption coefficient.

Medical Imaging 2016: Ultrasonic Imaging and Tomography, 2016

investigation of the dosimetric effect of the Autoscan ultrasound probe for guidance in radiother... more investigation of the dosimetric effect of the Autoscan ultrasound probe for guidance in radiotherapy," Proc.

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.

Journal of Medical Imaging, 2018

Elastography measures tissue strain, which can be interpreted under certain simplifying assumptio... more Elastography measures tissue strain, which can be interpreted under certain simplifying assumptions to be representative of the underlying stiffness distribution. This is useful in cancer diagnosis where tumors tend to have a different stiffness to healthy tissue and has also shown potential to provide indication of the degree of bonding at tumor-tissue boundaries, which is clinically useful because of its dependence on tumor pathology. We consider the changes in axial strain for the case of a symmetrical model undergoing uniaxial compression, studied by characterizing changes in tumor contrast transfer efficiency (CTE), inclusion to background strain contrast and strain contrast generated by slip motion, as a function of Young's modulus contrast and applied strain. We present results from a finite element simulation and an evaluation of these results using tissue-mimicking phantoms. The simulation results show that a discontinuity in displacement data at the tumor boundary, caused by the surrounding tissue slipping past the tumor, creates a halo of "pseudostrain" across the tumor boundary. Mobile tumors also appear stiffer on elastograms than adhered tumors, to the extent that tumors that have the same Young's modulus as the background may in fact be visible as low-strain regions, or those that are softer than the background may appear to be stiffer than the background. Tumor mobility also causes characteristic strain heterogeneity within the tumor, which exhibits low strain close to the slippery boundary and increasing strain toward the center of the tumor. These results were reproduced in phantom experiments. In addition, phantom experiments demonstrated that when fluid lubrication is present at the boundary, these effects become applied strain-dependent as well as modulus-dependent, in a systematic and characteristic manner. The knowledge generated by this study is expected to aid interpretation of clinical strain elastograms by helping to avoid misinterpretation as well as provide additional diagnostic criteria stated in the paper and stimulate further research into the application of elastography to tumor mobility assessment.

2019 IEEE International Ultrasonics Symposium (IUS), 2019

In this study, a photoacoustic super-resolution imaging technique was developed through imaging t... more In this study, a photoacoustic super-resolution imaging technique was developed through imaging the activation of Cyanine 7.5-coated phase-change nanodroplets using a preclinical photoacoustic imaging system and localizing the activated droplets. As a proof-of-concept experiment, photoacoustic images of flowing dye-coated nanodroplets in microfluidic channels were obtained with a cylindrically focused curved-array. Experimental results showed that super-resolution images can resolve the microfluidic channels which cannot be resolved by conventional beamformed images. The results also showed that the dye-coated phase-change nanodroplets can be optically activated in vivo and the activation signals can be separated from the image background by applying singular value decomposition filtering, and be used for further superlocalization processing. Such nanodroplets can offer better biocompatibility, as well as more flexible and controllable droplet activation rates, with potential for super-resolution imaging of static and extravascular targets, compared to existing contrast agents used in existing localization-based photoacoustic superresolution imaging techniques.

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 DDD 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 sim100,000\sim 100, 000sim100,000 parallel microtubes, each 200mutextm200\mu \text{m}200mutextm 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...

Frontiers in Pharmacology, 2019

Cancer Research, 2019

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 ...

Ultrasound in Medicine & Biology, 2011

This paper presents a new method for acquiring 3D volumes of ultrasonic axial strain data. The me... more This paper presents a new method for acquiring 3D volumes of ultrasonic axial strain data. The method uses a mechanically-swept probe to sweep out a single volume while applying a continuously varying axial compression. We examine the image quality and ease of use of the new method with in vitro and in vivo experiments. The new method is easier to use than the current best alternative and so more reliably produces images of superior quality.

Frontiers in Physics, 2021

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...

2017 IEEE International Ultrasonics Symposium (IUS), 2017

2019 IEEE International Ultrasonics Symposium (IUS), 2019

Contrast-enhanced photoacoustic imaging has shown a great potential in various medical imaging ap... more Contrast-enhanced photoacoustic imaging has shown a great potential in various medical imaging applications. Although different types of customized contrast agents were developed over the decade, there is no commercial FDA-approved photoacoustic imaging contrast agents. This study shows the in vivo photoacoustic imaging of low-boiling-point phase-change nanodroplets, made using ingredients from an existing commercial microbubble ultrasound contrast agents without any dye coated, in a mouse to demonstrate that commercial ultrasound contrast agents may have the potential to be used to facilitate the clinical translation of photoacoustic imaging. Decafluorobutane-core lipid-shell nanodroplets were manufactured. The homemade decafluorobutane droplet solution has the same core composition as the commercial MicroMarker© (FUJIFILM, Visualsonics) and Sonazoid© (GE Healthcare) contrast microbubbles. The results show that, after activation, signals from the spleen region have been significantly enhanced. As the droplets do not have any dye coating on the surface, one potential reason for the photo-activation of the droplets could be that the blood cells nearby absorb energy from the light. As the ingredients of the droplets are the same as some existing commercial microbubble contrast agents, this study demonstrates that droplets made from condensed commercial bubbles may have the potential to be used to facilitate the clinical translation of contrast-enhanced photoacoustic imaging.

Frontiers in Pharmacology, 2020

agent and that ultrasound contrast enhancement during or before ACT treatment may be employed as ... more agent and that ultrasound contrast enhancement during or before ACT treatment may be employed as a biomarker of therapeutic response during clinical use.

Cochrane Database of Systematic Reviews, 2018

How up-to-date is this review? The review authors searched for and used studies published up to A... more How up-to-date is this review? The review authors searched for and used studies published up to August 2016. *In these studies biopsy was the reference standard (means of establishing the final diagnosis). High-frequency ultrasound for diagnosing skin cancer in adults (Review)

AccessScience

A photoacoustic (PA) spectroscopy system has been built to study the differences between the PA s... more A photoacoustic (PA) spectroscopy system has been built to study the differences between the PA spectra of oxygenated and deoxygenated blood, and various PA contrast agents, with a view to optimising the identification of these media in clinical PA images. A variable-wavelength laser delivers short (ns) pulses of light, via a fibre optic cable, into a sample held between 75 µm transparent membranes. The optical wavelength is controlled by a computer, which scans the wavelength range 400-700 nm using a different pulse for each wavelength. Each pulse causes the sample to momentarily expand and emit a pressure wave, the energy of which is measured by the computer using a digital oscilloscope that samples the signal from a strongly focused 7.5 MHz ultrasound transducer. The resulting optical spectra are corrected for some system variables, such as the wavelengthdependent laser energy. Further corrections are planned, so that the measurement is truly of optical absorption coefficient at each wavelength. Even without these additional corrections however, the measured PA spectrum of oxygenated blood strongly resembles the published optical absorption spectrum. These results suggest that, in addition to its intended use for determining the optimum wavelengths for clinical PA imaging of blood oxygenation level and contrast agent concentration, this system may have applications as a laboratory spectrophotometer. Unlike traditional transmission spectrophotometers, which measure the extinction coefficient, the PA spectrometer will measure the absorption coefficient. This will make it suitable for use with (a) optically dark samples such as normal blood, which cannot be analysed in a standard spectrophotometer without dilution, and (b) turbid media, which normally require an optical scattercorrection to convert the extinction coefficient to an absorption coefficient.

Medical Imaging 2016: Ultrasonic Imaging and Tomography, 2016

investigation of the dosimetric effect of the Autoscan ultrasound probe for guidance in radiother... more investigation of the dosimetric effect of the Autoscan ultrasound probe for guidance in radiotherapy," Proc.

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.

Journal of Medical Imaging, 2018

Elastography measures tissue strain, which can be interpreted under certain simplifying assumptio... more Elastography measures tissue strain, which can be interpreted under certain simplifying assumptions to be representative of the underlying stiffness distribution. This is useful in cancer diagnosis where tumors tend to have a different stiffness to healthy tissue and has also shown potential to provide indication of the degree of bonding at tumor-tissue boundaries, which is clinically useful because of its dependence on tumor pathology. We consider the changes in axial strain for the case of a symmetrical model undergoing uniaxial compression, studied by characterizing changes in tumor contrast transfer efficiency (CTE), inclusion to background strain contrast and strain contrast generated by slip motion, as a function of Young's modulus contrast and applied strain. We present results from a finite element simulation and an evaluation of these results using tissue-mimicking phantoms. The simulation results show that a discontinuity in displacement data at the tumor boundary, caused by the surrounding tissue slipping past the tumor, creates a halo of "pseudostrain" across the tumor boundary. Mobile tumors also appear stiffer on elastograms than adhered tumors, to the extent that tumors that have the same Young's modulus as the background may in fact be visible as low-strain regions, or those that are softer than the background may appear to be stiffer than the background. Tumor mobility also causes characteristic strain heterogeneity within the tumor, which exhibits low strain close to the slippery boundary and increasing strain toward the center of the tumor. These results were reproduced in phantom experiments. In addition, phantom experiments demonstrated that when fluid lubrication is present at the boundary, these effects become applied strain-dependent as well as modulus-dependent, in a systematic and characteristic manner. The knowledge generated by this study is expected to aid interpretation of clinical strain elastograms by helping to avoid misinterpretation as well as provide additional diagnostic criteria stated in the paper and stimulate further research into the application of elastography to tumor mobility assessment.

2019 IEEE International Ultrasonics Symposium (IUS), 2019

In this study, a photoacoustic super-resolution imaging technique was developed through imaging t... more In this study, a photoacoustic super-resolution imaging technique was developed through imaging the activation of Cyanine 7.5-coated phase-change nanodroplets using a preclinical photoacoustic imaging system and localizing the activated droplets. As a proof-of-concept experiment, photoacoustic images of flowing dye-coated nanodroplets in microfluidic channels were obtained with a cylindrically focused curved-array. Experimental results showed that super-resolution images can resolve the microfluidic channels which cannot be resolved by conventional beamformed images. The results also showed that the dye-coated phase-change nanodroplets can be optically activated in vivo and the activation signals can be separated from the image background by applying singular value decomposition filtering, and be used for further superlocalization processing. Such nanodroplets can offer better biocompatibility, as well as more flexible and controllable droplet activation rates, with potential for super-resolution imaging of static and extravascular targets, compared to existing contrast agents used in existing localization-based photoacoustic superresolution imaging techniques.

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 DDD 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 sim100,000\sim 100, 000sim100,000 parallel microtubes, each 200mutextm200\mu \text{m}200mutextm 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...

Frontiers in Pharmacology, 2019

Cancer Research, 2019

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...