Bracco Suisse Sa

Bracco International Bv

Bracco Research Sa

Acuson Corporation

Peter Frinking

Marcel Arditi

Nicolas Rognin

Emmanuel Gaud

Michel Schneider

Philippe Bussat

Laurent Mercier

Feng Yan

Christian Guillot

Anne Lassus

Tristan Messager

Gilles Casqueiro

Tim Segers

Sibylle Pochon

Samir Cherkaoui

Thierry Bettinger

Eric Allemann

Jean-Marc Hyvelin

Ilaria Gori

Sophie Mehier-Humbert

Thomas Fresneau

Nathalie Biolluz

Nico DeJong

Nicolas Bracco Research Sa Rognin

A method for preparing a suspension of 'size-controlled' gas-filled microvesicles by microfluidic manufacturing techniques, which comprises using a gaseous flow comprising a first gas having high solubility in water and a second gas having low 5 solubility in water.

Preparation of size-controlled microvesicles

An embodiment includes analyzing a body part perfused with a contrast agent, which has been pre-administered as a bolus to circulate through the body-part with at least a first passage during an analysis interval. The analyzing includes providing at least one input signal indicative of a response to an interrogation signal of a corresponding location of the body part during the analysis interval, and fitting each input signal over the analysis interval by an instance of a combined bolus function of time, based on a combination of a first simple bolus function of time modeling the first passage of the contrast agent and at least one second simple bolus function of time each one modeling a corresponding second passage of the contrast agent.

Initialization of fitting parameters for perfusion assessment based on bolus administration

A method for preparing a suspension of size-controlled microparticles stabilized by a layer of amphiphilic material. The method, which may be applied to preparations using microfluidic techniques, comprises controlling the temperature of the microparticles during the preparation process and preferably while collecting the formed microparticles.

Preparation of size-controlled microparticles

A solution is proposed for analyzing a body-part of a patient, the body-part having been perfused before performing the method with a contrast agent capable of circulating within the patient and of being substantially immobilized on a biological target. A corresponding method comprises providing at least one filtered image comprising a plurality of filtered values for corresponding locations of the body-part, each filtered value comprising an indication of the immobilized contrast agent at the corresponding location with a contribution of the circulating contrast agent being substantially reduced, generating a thresholded image comprising a plurality of thresholded values corresponding to the filtered values, the thresholded image being generated by setting each thresholded value to the corresponding filtered value or to a reset value according to a comparison of the filtered value with an amplitude threshold, providing a plurality of candidate thresholds defined by corresponding candidate values of the amplitude threshold, generating a plurality of candidate images corresponding to the candidate thresholds each one comprising a plurality of candidate values corresponding to the filtered values, each candidate image being generated by setting each candidate value to the corresponding filtered value or to the reset value according to said comparison of the filtered value with the candidate threshold, calculating a plurality of comparison values corresponding to the candidate images, the comparison value of each candidate image being calculated according to a further comparison between the candidate values in an immobilization region corresponding to a group of locations containing a significant amount of the immobilized contrast agent and the candidate values in a circulation region corresponding to at least part of the locations excluding the immobilization region, determining a peak of the comparison values, and setting the amplitude threshold according to the peak of the comparison values.

Detection of immobilized contrast agent with dynamic thresholding

A method is provided for use with an ultrasound scanner, wherein an estimate value (particularly, a power level of the ultrasound scanner that is required to apply a desired acoustic pressure level to the body-part, the acoustic pressure level that is actually applied to the body-part when a specific power level is set, an acoustic attenuation that occurs within a patient between a transducer of the ultrasound scanner and the body-part and/or the acoustic attenuation that occurs within the patient between different body-parts) is determined according to a comparison between measurement data (based on a measurement response comprising a non-fundamental component of a measurement echo signal received in response to a measurement excitation signal) and corresponding reference data. Corresponding computer program product, system, therapeutic method, and diagnostic method are also provided.

Estimation of acoustic level in-situ with non-fundamental analysis

A solution for diagnostic applications is proposed. Particularly, a corresponding diagnostic system includes means (-) for providing (A-A) a plurality of input signals representative of a body-part being perfused with a contrast agent over time, each input signal being indicative of a response to an interrogating stimulus of a corresponding location of the body-part possibly including the contrast agent, means (-) for generating (A-A) a plurality of filtered signals from selected input signals of selected locations, each filtered signal at each instant over time being generated from a corresponding selected input signal according to a portion of the selected input signal including said instant, and means (-) for monitoring (A-A) each filtered signal to detect a peak in the response to the interrogation stimulus of the corresponding selected location, the peak being detected in response to the fulfillment of a stability condition by a corresponding portion of the filtered signal.

Real-time perfusion imaging and quantification

The present invention relates to a new composition comprising gas-filled microvesicles for contrast imaging which are particularly suitable for providing an effective echo response to at least two selected ultrasound waves having different frequencies. Said composition preferably comprises at least two different preparations of gas-filled microvesicles having respective peaks of non-linear echographic response differing by at least 2 MHz to each other, and preferably have respective size distributions with different median sizes. In particular, said preparations preferably have size distributions with respective Dvalues differing from each other by at least 0.5 &#x3bc;m, more preferably at least 1.0 &#x3bc;m. Alternatively, said composition has a volume size distribution showing a value of Bowley skewness of 0.16 or higher. According to a preferred embodiment, at least 95% of the total volume of gas contained in said microvesicles, calculated on the population of microvesicles up to a diameter of 10 &#x3bc;m, is contained in microvesicles having a diameter of 8 micron or less.

Gas-filled microvesicles composition for contrast imaging

An embodiment of a segmentation solution for use in diagnostic imaging applications is proposed. A corresponding embodiment of a data-processing segmentation method comprises: providing a representation over a non-zero analysis time period of a body-part being perfused with a contrast agent, the representation comprising, for each location of a set of locations of the body-part, an indication of a response over the analysis time period of the location to an interrogation signal; calculating, for each selected location of a set of selected locations, the value of at least one statistical parameter of a statistical distribution of the response over the analysis time period of the selected location, the set of selected locations comprising all the locations or a part thereof; and segmenting the selected locations according to a comparison between the values of said at least one statistical parameter for the selected locations with at least one segmentation threshold.

Segmentation in diagnostic imaging applications based on statistical analysis over time

Composition comprising gas filled microcapsules and a bioactive agent, useful for an ultrasound-mediated delivery of said bioactive agent. The microcapsules comprise a relatively stiff shell of polymeric or lipid material and have in particular a resistance to a mechanical index of at least 0.15, while the bioactive agent is substantially unbound to the shell of the microcapsules. The composition of the invention is particularly suitable for effectively delivering a genetic material into a cell, upon exposure of the composition to a level of acoustic pressure capable of destroying a portion of the microcapsules and releasing the gas contained therein.

Composition comprising gas-filled microcapsules for ultrasound mediated delivery

A data-processing method includes providing a parametric map including a plurality of parameter values, each one characterizing a corresponding location of a body-part. The method includes determining at least one statistical indicator of at least one distribution of a plurality of analysis parameter values corresponding to selected analysis locations, each statistical indicator being indicative of a condition of an analysis region of the body-part defined by the analysis locations.

Auto-scaling of parametric images

The present invention relates to a new composition comprising gas-filled microvesicles for contrast imaging which are particularly suitable for providing an effective echo response to at least two selected ultrasound waves having different frequencies. Said composition preferably comprises at least two different preparations of gas-filled microvesicles having respective peaks of non-liner echographic response differing by at least 2 MHz to each other, and preferably have respective size distributions with different mean sizes. In particular, said preparations preferably have size distributions with respective Dvalues differing from each other by at least 0.5 &#x3bc;m, more preferably at least 1.0 &#x3bc;m. Alternatively, said composition has a volume size distribution showing a value of Bowley skewness of 0.16 or higher. According to a preferred embodiment, at least 95% of the total volume of gas contained in said microvesicles, calculated on the population of microvesicles up to a diameter of 10 &#x3bc;m, is contained in microvesicles having a diameter of 8 micron or less.

A system for facilitating the detection of an immobilized contrast agent in medical imaging applications is proposed. The system includes means for providing a sequence of a total number of input images obtained at corresponding acquisition instants by imaging a body-part of a patient subjected to an administration of a contrast agent capable of circulating within the patient and of being substantially immobilized on a biological target, each input image including a plurality of input values each one indicative of a response to an interrogation signal of a corresponding portion of the body-part possibly including said contrast agent, and means for reducing a contribution of the circulating contrast agent within the body-part in at least one selected input image; the means for reducing includes means for creating a filtered image corresponding to each selected input image by replacing a set of input values of the selected input image with a set of corresponding filtered values, each filtered value being representative of the lowest response of the corresponding portion of the body-part in a set of multiple input images including the selected input image, the set of multiple input images consisting of a number of input images lower than the total number.

Detection of immobilized contrast agent in medical imaging applications based on flow dynamics analysis

An embodiment analyzes a body part of a patient, which patient is perfused with a contrast agent that is capable of circulating within the patient and of being substantially immobilized on a biological target. An embodiment of a corresponding system provides an echo signal that is indicative of a response over time to an interrogation signal of the body part, fits the echo signal with a time model function that models an evolution over time of the contrast agent in the body part, the time model function including a combination of a circulation function that models the circulation of the contrast agent and a decay function that models a decay of the echo signal from the immobilized contrast agent, and estimates at least one kinetics indicator of the contrast agent from the time model function.

Quantification analysis of immobilized contrast agent in medical imaging applications

An embodiment for analyzing a body-part of a patient is proposed. A corresponding data-processing method includes the steps of providing a sequence of input images representing the body-part over an analysis period, each input image including a set of input values each one being indicative of a response to an interrogation signal of a corresponding location of the body-part at a corresponding acquisition instant included in the analysis period, associating an analysis function of time with each one of a set of selected locations, the analysis function modeling a trend of the input values of the selected location in the sequence of input images, and providing a reference function of time for the analysis functions; in an embodiment, the data-processing method further includes comparing the analysis function of each selected location with the reference function to determine a polarity trend representing a trend over the analysis period of a polarity of a divergence between the analysis function of the selected location and the reference function, and creating a parametric image including a parametric value for each selected location, the parametric value being indicative of the polarity trend of the selected location.

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Geneva, Switzerland

Peter Frinking