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1.
Ultrasound Med Biol ; 45(9): 2444-2455, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31208880

RESUMO

Ultrasound contrast imaging has been used to assess tumour growth and regression by assessing the flow through the macro- and micro-vasculature. Our aim was to differentiate the blood kinetics of vessels such as veins, arteries and microvasculature within the limits of the spatial resolution of contrast-enhanced ultrasound imaging. The highly vascularised ovine ovary was used as a biological model. Perfusion of the ovary with SonoVue was recorded with a Philips iU22 scanner in contrast imaging mode. One ewe was treated with prostaglandin to induce vascular regression. Time-intensity curves (TIC) for different regions of interest were obtained, a lognormal model was fitted and flow parameters calculated. Parametric maps of the whole imaging plane were generated for 2 × 2 pixel regions of interest. Further analysis of TICs from selected locations helped specify parameters associated with differentiation into four categories of vessels (arteries, veins, medium-sized vessels and micro-vessels). Time-dependent parameters were associated with large veins, whereas intensity-dependent parameters were associated with large arteries. Further development may enable automation of the technique as an efficient way of monitoring vessel distributions in a clinical setting using currently available scanners.


Assuntos
Ovário/irrigação sanguínea , Ovário/diagnóstico por imagem , Ultrassonografia Doppler/métodos , Animais , Meios de Contraste , Feminino , Técnicas In Vitro , Fosfolipídeos , Reprodutibilidade dos Testes , Ovinos , Hexafluoreto de Enxofre
2.
Invest Radiol ; 54(8): 500-516, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31058661

RESUMO

OBJECTIVES: The aim of this study was to provide an ultrasound-based super-resolution methodology that can be implemented using clinical 2-dimensional ultrasound equipment and standard contrast-enhanced ultrasound modes. In addition, the aim is to achieve this for true-to-life patient imaging conditions, including realistic examination times of a few minutes and adequate image penetration depths that can be used to scan entire organs without sacrificing current super-resolution ultrasound imaging performance. METHODS: Standard contrast-enhanced ultrasound was used along with bolus or infusion injections of SonoVue (Bracco, Geneva, Switzerland) microbubble (MB) suspensions. An image analysis methodology, translated from light microscopy algorithms, was developed for use with ultrasound contrast imaging video data. New features that are tailored for ultrasound contrast image data were developed for MB detection and segmentation, so that the algorithm can deal with single and overlapping MBs. The method was tested initially on synthetic data, then with a simple microvessel phantom, and then with in vivo ultrasound contrast video loops from sheep ovaries. Tracks detailing the vascular structure and corresponding velocity map of the sheep ovary were reconstructed. Images acquired from light microscopy, optical projection tomography, and optical coherence tomography were compared with the vasculature network that was revealed in the ultrasound contrast data. The final method was applied to clinical prostate data as a proof of principle. RESULTS: Features of the ovary identified in optical modalities mentioned previously were also identified in the ultrasound super-resolution density maps. Follicular areas, follicle wall, vessel diameter, and tissue dimensions were very similar. An approximately 8.5-fold resolution gain was demonstrated in vessel width, as vessels of width down to 60 µm were detected and verified (λ = 514 µm). Best agreement was found between ultrasound measurements and optical coherence tomography with 10% difference in the measured vessel widths, whereas ex vivo microscopy measurements were significantly lower by 43% on average. The results were mostly achieved using video loops of under 2-minute duration that included respiratory motion. A feasibility study on a human prostate showed good agreement between density and velocity ultrasound maps with the histological evaluation of the location of a tumor. CONCLUSIONS: The feasibility of a 2-dimensional contrast-enhanced ultrasound-based super-resolution method was demonstrated using in vitro, synthetic and in vivo animal data. The method reduces the examination times to a few minutes using state-of-the-art ultrasound equipment and can provide super-resolution maps for an entire prostate with similar resolution to that achieved in other studies.


Assuntos
Meios de Contraste , Aumento da Imagem/métodos , Microvasos/diagnóstico por imagem , Ovário/irrigação sanguínea , Ovário/diagnóstico por imagem , Fosfolipídeos , Hexafluoreto de Enxofre , Ultrassonografia/métodos , Algoritmos , Animais , Feminino , Humanos , Técnicas In Vitro , Microbolhas , Modelos Animais , Imagens de Fantasmas , Ovinos
3.
IEEE Trans Med Imaging ; 38(1): 194-204, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30059295

RESUMO

Minimum Variance (MV) beamforming is known to improve the lateral resolution of ultrasound images and enhance the separation of isolated point scatterers. This paper aims to evaluate the adaptive beamformer's performance with flowing microbubbles (MBs) which are relevant to super-resolution ultrasound imaging. Simulations using point scatterer data from single emissions were complemented by an experimental investigation performed using a capillary tube phantom and the Synthetic Aperture Real-time Ultrasound System (SARUS). The MV performance was assessed by the minimum distance that allows the display of two scatterers positioned side-by-side, the lateral Full-Width-at-Half-Maximum (FWHM), and the Peak-Sidelobe-Level (PSL). In the tube, scatterer responses separated by down to [Formula: see text] (or 1.05λ ) were distinguished by the MV method, while the standard Delay-And-Sum (DAS) beamformers were unable to achieve such separation. Up to ninefold FWHM decrease was also measured in favor of the MV beamformer for individual echoes from MBs. The lateral distance between two scatterers impacted on their FWHM value, and additional differences in the scatterers' axial or out-of-plane position also impacted on their size and appearance. The simulation and experimental results were in agreement in terms of lateral resolution. The point scatterer study showed that the proposed MV imaging scheme provided clear resolution benefits compared to DAS. Current super-resolution methods mainly depend on DAS beamformers. Instead, the use of the MV method may provide a larger number of detected, and potentially better localized, MB scatterers.


Assuntos
Processamento de Imagem Assistida por Computador/métodos , Processamento de Sinais Assistido por Computador , Ultrassonografia/métodos , Microbolhas , Imagens de Fantasmas
4.
Artigo em Inglês | MEDLINE | ID: mdl-30028698

RESUMO

Contrast echocardiography (CE) ultrasound with microbubble contrast agents has significantly advanced our capability for assessment of cardiac function, including myocardium perfusion quantification. However, in standard CE techniques obtained with line by line scanning, the frame rate and image quality are limited. Recent research has shown significant frame-rate improvement in noncontrast cardiac imaging. In this work, we present and initially evaluate, both in vitro and in vivo, a high-frame-rate (HFR) CE imaging system using diverging waves and pulse inversion sequence. An imaging frame rate of 5500 frames/s before and 250 frames/s after compounding is achieved. A destruction-replenishment sequence has also been developed. The developed HFR CE is compared with standard CE in vitro on a phantom and then in vivo on a sheep heart. The image signal-to-noise ratio and contrast between the myocardium and the chamber are evaluated. The results show up to 13.4-dB improvement in contrast for HFR CE over standard CE when compared at the same display frame rate even when the average spatial acoustic pressure in HFR CE is 36% lower than the standard CE. It is also found that when coherent compounding is used, the HFR CE image intensity can be significantly modulated by the flow motion in the chamber.


Assuntos
Ecocardiografia/métodos , Coração/diagnóstico por imagem , Processamento de Imagem Assistida por Computador/métodos , Animais , Meios de Contraste/química , Feminino , Microbolhas , Imagens de Fantasmas , Ovinos , Razão Sinal-Ruído
5.
Ultrasonics ; 70: 84-91, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27140502

RESUMO

This paper investigated the influence of needle gauge (19G and 27G), injection rate (0.85ml·min(-1), 3ml·min(-1)) and temperature (room temperature (RT) and body temperature (BT)) on the mean diameter, concentration, acoustic attenuation, contrast to tissue ratio (CTR) and normalised subharmonic intensity (NSI) of three ultrasound contrast agents (UCAs): Definity, SonoVue and MicroMarker (untargeted). A broadband substitution technique was used to acquire the acoustic properties over the frequency range 17-31MHz with a preclinical ultrasound scanner Vevo770 (Visualsonics, Canada). Significant differences (P<0.001-P<0.05) between typical in vitro setting (19G needle, 3ml·min(-1) at RT) and typical in vivo setting (27G needle, 0.85ml·min(-1) at BT) were found for SonoVue and MicroMarker. Moreover we found that the mean volume-based diameter and concentration of both SonoVue and Definity reduced significantly when changing from typical in vitro to in vivo experimental set-ups, while those for MicroMarker did not significantly change. From our limited measurements of Definity, we found no significant change in attenuation, CTR and NSI with needle gauge. For SonoVue, all the measured acoustic properties (attenuation, CTR and NSI) reduced significantly when changing from typical in vitro to in vivo experimental conditions, while for MicroMarker, only the NSI reduced, with attenuation and CTR increasing significantly. These differences suggest that changes in physical compression and temperature are likely to alter the shell structure of the UCAs resulting in measureable and significant changes in the physical and high frequency acoustical properties of the contrast agents under typical in vitro and preclinical in vivo experimental conditions.


Assuntos
Meios de Contraste/administração & dosagem , Meios de Contraste/química , Injeções/instrumentação , Agulhas , Ondas Ultrassônicas , Ultrassonografia/métodos , Meios de Contraste/efeitos da radiação , Desenho de Equipamento , Análise de Falha de Equipamento , Teste de Materiais , Tamanho da Partícula , Reprodutibilidade dos Testes , Espalhamento de Radiação , Sensibilidade e Especificidade , Temperatura , Ultrassonografia/instrumentação
6.
Artigo em Inglês | MEDLINE | ID: mdl-26736218

RESUMO

Microbubbles are used in medical ultrasound imaging as contrast agents to image the vascular bed under the mode of Ultrasound Contrast Imaging (UCI). The microbubble shell determines the acoustic response and hence the signal that is utilized to form the images in UCI. Single microbubble signals from BiSphere™ (POINT Biomedical, San Carlos, CA, USA) microbubbles were captured using a clinical ultrasound system. Three main typical responses of microbubbles were identified, a) full duration echo, b) echo with duration shorter than the incident pulse and c) echo that in part resembles that in (b) and in addition prior to that another short duration initial lower amplitude signal. These data corroborate that the shell structural and nanomechanical property provide the different responses at different microbubble sizes. These different signals present an opportunity for tracking the movement of well differentiated single microbubbles particularly with novel super-resolution imaging methods that require sparse microbubble populations.


Assuntos
Acústica , Meios de Contraste , Microbolhas , Ultrassonografia/métodos , Acústica/instrumentação , Meios de Contraste/química , Diagnóstico por Imagem , Desenho de Equipamento , Humanos , Ultrassonografia/instrumentação
7.
PLoS One ; 9(10): e111280, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25343339

RESUMO

In order to develop a medical alternative to surgical ovarian diathermy (OD) in polycystic ovary syndrome (PCOS) more mechanistic information is required about OD. We therefore studied the cellular, molecular and vascular effects of diathermy on the ovary using an established ovine model of PCOS. Pregnant sheep were treated twice weekly with testosterone propionate (100 mg) from day 30-100 gestation. Their female offspring (n = 12) were studied during their second breeding season when the PCOS-like phenotype, with anovulation, is fully manifest. In one group (n = 4) one ovary underwent diathermy and it was collected and compared to the contralateral ovary after 24 hours. In another group a treatment PCOS cohort underwent diathermy (n = 4) and the ovaries were collected and compared to the control PCOS cohort (n = 4) after 5 weeks. Ovarian vascular indices were measured using contrast-enhanced ultrasound and colour Doppler before, immediately after, 24 hours and five weeks after diathermy. Antral follicles were assessed by immunohistochemistry and ovarian stromal gene expression by quantitative RT-PCR 24 hours and 5 weeks after diathermy. Diathermy increased follicular atresia (P<0.05) and reduced antral follicle numbers after 5 weeks (P<0.05). There was an increase in stromal CCL2 expression 24 hours after diathermy (P<0.01) but no alteration in inflammatory indices at 5 weeks. Immediately after diathermy there was increased microbubble transit time in the ovarian microvasculature (P = 0.05) but this was not seen at 24 hours. However 24 hours after diathermy there was a reduction in the stromal Doppler blood flow signal (P<0.05) and an increased ovarian resistance index (P<0.05) both of which persisted at 5 weeks (P<0.01; P<0.05). In the ovine model of PCOS, OD causes a sustained reduction in ovarian stromal blood flow with an increased ovarian artery resistance index associated with atresia of antral follicles.


Assuntos
Diatermia , Ovário/patologia , Síndrome do Ovário Policístico/terapia , Animais , Biomarcadores/metabolismo , Modelos Animais de Doenças , Feminino , Estudos de Associação Genética , Inflamação/patologia , Microbolhas , Folículo Ovariano/patologia , Ovário/irrigação sanguínea , Ovário/diagnóstico por imagem , Ovário/fisiopatologia , Síndrome do Ovário Policístico/sangue , Síndrome do Ovário Policístico/diagnóstico por imagem , Síndrome do Ovário Policístico/fisiopatologia , Gravidez , Progesterona/sangue , Reação em Cadeia da Polimerase em Tempo Real , Carneiro Doméstico , Ultrassonografia Doppler
8.
Artigo em Inglês | MEDLINE | ID: mdl-25569942

RESUMO

Ultrasound contrast agents are gas filled microbubbles which produced enhanced echoes in ultrasound imaging thus allowing the acquisition of detailed information on the path of blood. It is theoretically known that the size of a vessel affects the behavior of a microbubble, which could potentially be used to discriminate different sized vessels. This information would be useful in the monitoring of neovascularization in tumor growth or treatment. However, currently it is not possible to identify the vessel diameter by any means of signal processing of microbubble echoes. In order to assess microbubble behavior when confined in tubes we compared the acoustic backscatter from biSphere™ microbubbles both free in water and flowing in 200 µm diameter tubes that are similar in size to arterioles. Experimental systems that allow the interrogation of individual microbubbles were designed and modified to allow investigation of both free microbubbles and those in tubes. Unprocessed single microbubble RF data were collected, allowing the calculation of both the fundamental and second harmonic components of the backscattered signal. Microbubbles confined in tubes had lower amplitude response compared to unconfined microbubbles. On consecutive insonations of the same microbubble, free microbubbles produced echoes above noise more often than confined microbubbles. This setup may be used to investigate microbubble behavior in a range of smaller tubes with diameters similar to capillaries thus enabling signal processing design for vessel differentiation.


Assuntos
Acústica , Meios de Contraste , Microbolhas , Celulose , Hidrodinâmica , Movimento (Física) , Ultrassom
9.
Artigo em Inglês | MEDLINE | ID: mdl-25571134

RESUMO

Microvasculature density (MVD) provides an established biomarker for the prognosis of numerous diseases associated with abnormal microvascular networks. The accurate, robust and timely assessment of MVD changes facilitates disease detection, treatment monitoring and patient stratification. Nevertheless, the current gold standard (PET) for MVD quantification is not used in clinical practice due to its high costs and potential health hazards. Contrast Enhanced Ultrasound (CEUS) imaging can provide an attractive alternative. However, the limited dissociation between larger vessels and microvasculature in the imaged tissues limits the accuracy and robustness of CEUS. This study proposed a novel, and fully automatic technique that dissociates larger vessels from microvasculature in CEUS imaged tissues. The ovine Corpus Luteum (CL) was used as an in vivo model for the development and assessment of the proposed technique.


Assuntos
Corpo Lúteo/irrigação sanguínea , Microvasos/diagnóstico por imagem , Animais , Corpo Lúteo/diagnóstico por imagem , Feminino , Interpretação de Imagem Assistida por Computador , Fluxo Sanguíneo Regional , Ovinos , Processamento de Sinais Assistido por Computador , Ultrassonografia Doppler/métodos
10.
Ultrasound Med Biol ; 40(3): 541-50, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24361219

RESUMO

The acoustic properties of two clinical (Definity, Lantheus Medical Imaging, North Billerica, MA, USA; SonoVue, Bracco S.P.A., Milan, Italy) and one pre-clinical (MicroMarker, untargeted, Bracco, Geneva, Switzerland; VisualSonics, Toronto, ON, Canada) ultrasound contrast agent were characterized using a broadband substitution technique over the ultrasound frequency range 12-43 MHz at 20 ± 1°C. At the same number concentration, the acoustic attenuation and contrast-to-tissue ratio of the three native ultrasound contrast agents are comparable at frequencies below 30 MHz, though their size distributions and encapsulated gases and shells differ. At frequencies above 30 MHz, native MicroMarker has higher attenuation values and contrast-to-tissue ratios than native Definity and SonoVue. Decantation was found to be an effective method to alter the size distribution and concentration of native clinical microbubble populations, enabling further contrast enhancement for specific pre-clinical applications.


Assuntos
Meios de Contraste/química , Fluorocarbonos/química , Fosfolipídeos/química , Ultrassonografia/métodos , Meios de Contraste/efeitos da radiação , Fluorocarbonos/efeitos da radiação , Ondas de Choque de Alta Energia , Humanos , Tamanho da Partícula , Imagens de Fantasmas , Fosfolipídeos/efeitos da radiação , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Hexafluoreto de Enxofre/química , Hexafluoreto de Enxofre/efeitos da radiação , Ultrassonografia/instrumentação
11.
Ultrasound Med Biol ; 38(7): 1262-70, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22502881

RESUMO

This study characterized the acoustic properties of an International Electromechanical Commission (IEC) agar-based tissue mimicking material (TMM) at ultrasound frequencies in the range 10-47 MHz. A broadband reflection substitution technique was employed using two independent systems at 21°C ± 1°C. Using a commercially available preclinical ultrasound scanner and a scanning acoustic macroscope, the measured speeds of sound were 1547.4 ± 1.4 m∙s(-1) and 1548.0 ± 6.1 m∙s(-1), respectively, and were approximately constant over the frequency range. The measured attenuation (dB∙cm(-1)) was found to vary with frequency f (MHz) as 0.40f + 0.0076f(2). Using this polynomial equation and extrapolating to lower frequencies give values comparable to those published at lower frequencies and can estimate the attenuation of this TMM in the frequency range up to 47 MHz. This characterisation enhances understanding in the use of this TMM as a tissue equivalent material for high frequency ultrasound applications.


Assuntos
Ágar/química , Materiais Biomiméticos/química , Ondas de Choque de Alta Energia , Imagens de Fantasmas , Espalhamento de Radiação , Ultrassonografia/métodos , Humanos
12.
Ultrasound Med Biol ; 31(4): 545-52, 2005 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-15831333

RESUMO

Ultrasonic contrast agents are currently being developed to target and bind to specific areas of interest such as atheromous plaque. A microbubble has been developed in-house which can be targeted to attach to specific cell-lines. To assess the feasibility of using the microbubble in vivo, the shear stresses which the bound microbubbles can withstand need to be known. A flow chamber was developed for use with intravascular ultrasound (IVUS) and laser Doppler anemometry (LDA). Biotin was incorporated into the microbubble shells and streptavidin was used to attach them to agar. IVUS at 40 MHz was then used to image the attached microbubbles under steady flow at a range of flow rates from 75 to 480 mL min(-1) through a flow area of 9 mm(2). LDA was employed to find high resolution velocity profiles of the flow in the chamber at a selection of these flow rates and the shear stresses on the bubbles were calculated. The bubbles were found to remain attached to the agar for shear stresses of up to 3.4 Pa. This compares with mean physiological arterial shear stresses of less than 1.5 Pa for pulsatile flow.


Assuntos
Fluxometria por Laser-Doppler , Ultrassonografia de Intervenção/métodos , Ágar , Arteriosclerose/diagnóstico por imagem , Biotina , Meios de Contraste , Humanos , Microbolhas , Fluxo Pulsátil , Reologia , Estreptavidina , Estresse Mecânico , Ultrassonografia de Intervenção/instrumentação
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