Thomas Gauthier

Inflammation within Carotid Atherosclerotic Plaque: Assessment with Late-Phase Contrast-enhanced US

PURPOSE To determine if the number of nontargeted microbubbles retained in human carotid plaque is sufficient to be detected with ultrasonography (US). MATERIALS AND METHODS The study protocol was approved by the local research ethics committee. Informed consent was obtained. A total of 37 subjects with carotid atherosclerosis (mean age, 69.9 years; age range, 49-86 years), of whom 27 (73%) were men (mean age, 69.7 years; age range, 58-86 years) and 10 (27%) were women (mean age, 70.3 years; age range, 49-86 years), were studied between December 2008 and May 2009 with late-phase (LP) contrast material-enhanced US by using flash imaging with a nonlinear mode at an intermediate mechanical index of 0.34 6 minutes after bolus contrast agent injection. Plaques were defined as symptomatic if symptoms consistent with stroke, transient ischemic attack, or amaurosis fugax had occurred in the neurovascular territory of the plaque studied within 12 months prior to entry into the study. Plaques were defined as asymptomatic if no such events had ever occurred within the neurovascular territory. Raw linear data were used to quantify echogenicity of the plaque, which was normalized to lumen echogenicity. Gray-scale median score was also calculated. RESULTS Of the 37 subjects, 16 (43%) had symptomatic plaques and 21 (57%) had asymptomatic plaques. All examinations yielded evaluable LP contrast-enhanced US data. Normalized LP plaque echogenicity was greater in the symptomatic group (0.39; 95% confidence interval: -0.11, 0.89) than in the asymptomatic group (0.69; 95% confidence interval: -1.04, -0.34) (P = .0005). There was a moderate (rho = -0.44, P = .016) inverse correlation between normalized LP plaque echogenicity and gray-scale median score. CONCLUSION By quantifying microbubble retention within the carotid plaque, LP contrast-enhanced US depicts clear differences between groups of subjects with plaque ipsilateral to symptoms and asymptomatic plaques. This technique has promise as a tissue-specific marker of inflammation and a potential role in the risk stratification of atherosclerotic carotid stenosis.

Perfusion quantification using dynamic contrast-enhanced ultrasound: The impact of dynamic range and gain on time–intensity curves

The objective of this study was to assess the impact of dynamic range and gain on perfusion quantification using linearized log-compressed data. An indicator-dilution experiment was developed with an in vitro flow phantom setup used with SonoVue contrast agent (Bracco SpA, Milan, Italy). Imaging was performed with a Philips iU22 scanner and a C5-1 curvilinear transducer using a contrast-specific nonlinear pulse sequence (power modulation) at 1.7MHz. Clinical dynamic contrast-enhanced ultrasound image loops of liver tumors were also collected for preliminary validation of the in vitro findings. Time-intensity curves were extracted from image loops with two different approaches: from linearized log-compressed data and from linear (uncompressed) data. The error of time-intensity curve parameters derived from linearized log-compressed data (deviation from linear data) was found to be less than 2.1% and 5.4% for all studied parameters in the in vitro experiment and in the clinical study, respectively, when a high dynamic range setting (at least 50dB on the iU22) is used. The gain must be carefully adjusted to ensure a high signal-to-noise ratio and to avoid signal saturation. From the time-intensity curve analysis it was also found that rise time of the bolus time-intensity curve is the least variable of all the studied time-intensity curve parameters.

Ultrasound-Based Elastography: A Novel Approach to Assess Radio Frequency Ablation of Liver Masses Performed With Expandable Ablation Probes A Feasibility Study

Objective. The purpose of this study was to evaluate the technical feasibility of ultrasound‐based elastography as a tool for assessing the size and shape of the coagulation necrosis caused by radio frequency ablation (RFA) probes using expandable electrodes ex vivo as well as in a patient with a liver metastasis. Methods. A commercially available expandable RFA probe was used to create a 3‐cm ablation in a piece of bovine liver. The ablation probe was used in situ to induce tissue deformation for elastography before and after ablation. Ultrasonic radio frequency data were processed to generate elasticity strain images. The appearance of the ablation zone was compared with magnetic resonance imaging and a gross section specimen. One patient with malignant metastatic disease to the liver and a clinical indication for RFA was investigated for the feasibility of percutaneous elastography of RFA using the same technique. Sonographic strain images were compared with the appearance of the nonenhancing ablation zone on contrast‐enhanced computed tomography. Results. Ex vivo, the ablation zone on ultrasound‐based elastography was represented by an area of increased stiffness and was well demarcated from the nonablated surrounding tissue. The size and shape of the ablated zone on the strain image correlated well with the gross specimen and the magnetic resonance imaging appearance. Strain images obtained from the patient showed results similar to those of the ex vivo experiment and correlated well with the nonenhancing area of ablation on contrast‐enhanced computed tomography. Conclusions. Ultrasound‐based elastography may be a promising tool for displaying the ablation zone created by expandable RFA probes.

Dynamic contrast enhanced ultrasound assessment of the vascular effects of novel therapeutics in early stage trials

AbstractImaging is key in the accurate monitoring of response to cancer therapies targeting tumour vascularity to inhibit its growth and dissemination. Dynamic contrast enhanced ultrasound (DCE ultrasound) is a quantitative method with the advantage of being non-invasive, widely available, portable, cost effective, highly sensitive and reproducible using agents that are truly intravascular. Under the auspices of the initiative of the Experimental Cancer Medicine Centre Imaging Network, bringing together experts from the UK, Europe and North America for a 2-day workshop in May 2010, this consensus paper aims to provide guidance on the use of DCE ultrasound in the measurement of tumour vascular support in clinical trials. Key Points• DCE ultrasound can quantify and extract specific blood flow parameters, such as flow velocity, relative vascular volume and relative blood flow rate.• DCE ultrasound can be performed repeatedly and is therefore ideally suited for pharmacokinetic and pharmacodynamic studies evaluating vascular-targeted drugs.• DCE ultrasound provides a reproducible method of assessing the vascular effects of therapy in pre-clinical and early clinical trials, which is easily translatable into routine clinical practice.

In vitro evaluation of the impact of ultrasound scanner settings and contrast bolus volume on time-intensity curves.

The objective of this study was to assess in vitro the impact of ultrasound scanner settings and contrast bolus volume on time-intensity curves formed from dynamic contrast-enhanced ultrasound image loops. An indicator-dilution experiment was developed with an in vitro flow phantom setup used with SonoVue contrast agent (Bracco SpA, Milan, Italy). Imaging was performed with a Philips iU22 scanner and two transducers (L9-3 linear and C5-1 curvilinear). The following ultrasound scanner settings were investigated, along with contrast bolus volume: contrast-specific nonlinear pulse sequence, gain, mechanical index, focal zone depth, acoustic pulse center frequency and bandwidth. Four parameters (rise time, mean transit time, peak intensity, and area under the curve) were derived from time-intensity curves which were obtained after pixel by pixel linearization of log-compressed data (also referred to as video data) included in a region of interest. Rise time was found to be the parameter least impacted by changes to ultrasound scanner settings and contrast bolus volume; the associated coefficient of variation varied between 0.7% and 6.9% while it varied between 0.8% and 19%, 12% and 71%, and 9.2% and 66%, for mean transit time, peak intensity, and area under the curve, respectively. The present study assessed the impact of ultrasound scanner settings and contrast bolus volume on time-intensity curve analysis. One should be aware of these issues to standardize their technique in each specific organ of interest and to achieve accurate, sensitive, and reproducible data using dynamic contrast-enhanced ultrasound. One way to mitigate the impact of ultrasound scanner settings in longitudinal, multi-center quantitative dynamic contrast-enhanced ultrasound studies may be to prohibit any adjustments to those settings throughout a given study. Further clinical studies are warranted to confirm the reproducibility and diagnostic or prognostic value of time-intensity curve parameters measurements in a particular clinical scenario of interest, for example that of cancer patients undergoing vascular targeting therapies.

Assessment of Global Liver Blood Flow With Quantitative Dynamic Contrast-Enhanced Ultrasound

This study assessed the potential of quantitative analysis of contrast bolus kinetics to reflect global liver blood flow.

Reproducibility of Quantitative Assessment of Altered Hepatic Hemodynamics With Dynamic Contrast-Enhanced Ultrasound

The aim of this clinical study was to evaluate the reproducibility of quantitative assessment of altered hepatic hemodynamics with dynamic contrast‐enhanced ultrasound.

P4B-5 The Role of Local Center Frequency Estimation in Doppler-Based Strain Imaging

Ultrasound frequency-dependent attenuation causes a downshift in the spectrum as ultrasound waves propagate through attenuating tissue. Therefore, assuming a constant center frequency in Doppler (autocorrelation) based strain imaging will result in displacement estimation error and ultimately affect strain values, especially when using broadband signals. Here we derive a theoretical expression, based on a Gaussian-enveloped pulse, for the strain estimation error due to errors in the assumed center frequency. The expression relates the strain estimation error to the attenuation coefficient, pulse center frequency, relative bandwidth, imaging depth, and true strain. For a 6 MHz transducer (50% BW) imaging tissue with attenuation coefficient 0.5 dB/MHz/cm, we show that the center frequency downshift introduces a range of -24% to -74% relative strain bias error from 2 cm to 6 cm depths, respectively. We support our theoretical derivations with Doppler-based strain estimation results using Field II simulations, phantom, and ex-vivo bovine liver experiments. In simulation, the localized-center-frequency-estimation (LCFE) based Doppler approach reduced the bias and variance of the strain estimates, as theoretically predicted. A Philips 6.2 MHz linear transducer was used to acquire high frame rate RF data on an elasticity phantom (0.5 dB/MHz/cm) under controlled compression. In three ROIs (5 mm axial times 13 mm lateral) centered at 2, 3, and 4 cm depths, the estimated strain values are -3.7%plusmn0.9%, -3.6%plusmn0.8%, and -2.6%plusmn0.9%, respectively, with LCFE, and -3.3%plusmn1.3%, -2.4%plusmn1.6%, and -1.6%plusmn2.0% without LCFE. Respectively, the relative biases between the two methods are -11%, -33% and -39%, close to the theoretical biases of -8%, -24% and -51%. Results on an ex-vivo liver phantom with a post RFA hard lesion show a 20% reduction in strain standard deviation at the lesion center (4.5 cm depth) when using LCFE. Experimental results show that for broadband ultrasound signals, LCFE is important in Doppler-based elasticity imaging to reduce the bias and variance of the strain estimates, thus providing more diagnostically accurate information.

Comparison of ultrasound strain images with multi-modality imaging techniques in liver RF ablation assessment: Initial ex vivo and clinical results

Ultrasound (US) elastography in liver imaging applications has recently gained interest in the clinical community. Various techniques explore the use of elasticity information for clinical diagnosis (for fibrosis-cirrhosis staging) and assessment of radiofrequency (RF) or High Intensity Focused Ultrasound (HIFU) ablation. In this paper, we conduct compression-based strain imaging for ex vivo and clinical liver RF ablation (RFA) assessment, using the RFA needle to induce the strain (method initially proposed by Varghese et al. in ex vivo porcine). The results are validated against several imaging modalities. Six ex vivo bovine livers were embedded in gelatin mixtures. A commercial RFA needle (Rita) was inserted and deployed into each liver sample. Radiofrequency (RF) ultrasound data were collected using Philips US systems during RFA needle pulling. Strain images were generated offline using 2D speckle tracking. Post- RFA strain images were compared to T1-weighted MRI (Philips). The livers were then dissected along the US image plane for caliper measurements. The elasticity images of the lesions exhibit a 40-fold contrast-to-noise Ratio (CNR) enhancement as compared to B-mode. The lesion sizes, as measured on the elasticity images, compared well with the MRI measurements (<10% error). Clinical RF data were acquired on two RFA patients with an iU-22 system (Philips). Both patients underwent pre- and post-operative contrast computed tomograpy (CT) imaging, and one also had intra-operative contrastenhanced ultrasound. Following RFA, no lesion could be clearly identified in the US B-mode images. Comparable lesion dimensions were measured from the intra-operative elasticity images and post-operative contrast CT. Elasticity imaging could provide similar information as contrast CT or contrast ultrasound imaging without the need for contrast or additional ionizing radiation. It also potentially allows for intra-operative monitoring of the RFA procedure, which in turn could lead to improved efficacy of RFA treatments.