SYSTEM FOR SCREENING TISSUE ON THE PRESENCE OF MALIGNANT CELLS

Abstract

A system for screening tissue on the presence of malignant cells in said tissue, which system comprises a wave detector and a data processing device connected or connectable to the wave detector for processing data received from the wave detector, which system comprises an actuator to excite the tissue which is suspected to comprise malignant cells, and the data processing device comprises an analyzer connected to the wave detector for analyzing the data received from the wave detector in response to the actuator exciting the tissue, which analyzer is arranged to identify the tissue with an elevated probability to comprise malignant cells in comparison with tissue that is not suspected to comprise malignant cells in an individual case. The inventors remark that the identification of high but symmetrical outcome results can be used in a population-based stratification of risk of developing malignant cells and can serve as a biomarker in risk-based screening approaches.

Claims

1. A system for screening tissue on the presence of malignant cells in said tissue, which system comprises: a wave detector; and a data processing device connected or connectable to the wave detector for processing data received from the wave detector; wherein, the system comprises an actuator to mechanically excite the tissue which is suspected to comprise malignant cells, and the data processing device comprises an analyzer connected to the wave detector for analyzing the data received from the wave detector in response to the actuator mechanically exciting the tissue, which analyzer is arranged to identify the tissue with an elevated probability to comprise malignant cells in comparison with tissue that is not suspected to comprise malignant cells.

2. The system of claim 1, wherein the analyzer determines from the data received from the wave detector an estimated stiffness value of the tissue under investigation, wherein the analyze is arranged to use this stiffness value as an indication for the presence or nonpresence of malignant cells.

3. The system of claim 2, wherein the analyzer determines from the data received from the wave detector local differences of estimated stiffness values of the tissue under investigation, wherein the analyzer is arranged to use these local differences of stiffness values as an indication for the presence or nonpresence of malignant cells.

4. The system of claim 1, wherein the data processing device comprises or connects to a data storage device for storage of data received from the wave detector.

5. The system of claim 1, wherein the analyzer is equipped to operate on data received from the wave detector and/or from the data storage device, wherein the data has different timestamps so as to enable a longitudinal comparison of data over time and to derive from this comparison an indication of the probable presence of malignant cells.

6. The system of claim 1, wherein the actuator is one of a sound emitter, an ultrasound emitter, a pulsed laser source, a displacement actuator.

7. The system of claim 6, wherein the displacement actuator is equipped with at least one marker which enables position detection of the tissue engaging surface or contact area of the displacement actuator, and that preferably a further detectable marker is provided on the supporting surface against which the displacement actuator presses the tissue under investigation.

8. The system of claim 1, wherein the actuator is a displacement actuator for displacing a tissue engaging surface along a predetermined path and/or applying a predetermined load on the tissue to be investigated.

9. The system of claim 8, wherein the wave detector is arranged to collect and provide data to the data processing device, said data relating at least to the tissue being disengaged and released from a load by the displacement actuator, and to the tissue being engaged and loaded by the displacement actuator to a predetermined full load.

10. The system of claim 8, wherein the data processing device is equipped to estimate from the data a contact area between the displacement actuator and the tissue during engagement of the tissue by the displacement actuator.

11. The system of claim 8, wherein the displacement actuator is equipped with a capacitive measurement organ to determine a contact area between the displacement actuator and the tissue during engagement of the tissue by the displacement actuator.

12. The system of claim 8, wherein the analyzer is arranged to derive an estimated stiffness value of the tissue from a measured or calculated force applied to the tissue by the displacement actuator and the estimated or measured contact area between the displacement actuator and the tissue during engagement of the tissue by the displacement actuator.

13. The system of claim 8, wherein the analyzer is arranged to derive an estimated stiffness value of the tissue from a longitudinal comparison of a measured or calculated force applied to the tissue by the displacement actuator over time, and the estimated or measured contact area developing over time between the displacement actuator and the tissue during engagement of the tissue by the displacement actuator.

14. The system claim 8, wherein the system is equipped with a position sensor for measuring a position of a tissue engaging surface or contact area of the displacement actuator and/or a force sensor for measuring a force that the displacement actuator provides to the tissue, which position sensor and/or force sensor are connected to the data processing device for use by the data processing device in combination with the estimated or measured contact area between the displacement actuator and the tissue during engagement of the tissue by the displacement actuator so as to arrange that the load applied by the displacement actuator to the tissue is normalized to a pressure which the displacement actuator applies to the tissue.

15. The system of claim 10, wherein the analyzer is arranged to derive an estimated stiffness value of the tissue from the estimated or measured contact area between the displacement actuator and the tissue during engagement of the tissue by the displacement actuator, or from a longitudinal comparison of the estimated or measured contact area developing over time and to derive from this comparison an indication of the presence of malignant cells.

16. The system of claim 10, wherein the estimation or measurement of the contact area between the displacement actuator and the tissue is monitored during a complete cycle of engaging and disengaging of the tissue by the displacement actuator.

17. The system of claim 10, wherein the analyzer is arranged to derive an estimated stiffness value of the tissue from a measured or calculated force applied to the tissue and at least one of the estimated volume of the tissue, the contact area between the displacement actuator and the tissue, and a projected area obtained from a projection of the volume of the tissue, one thing and another derived from the data when the displacement actuator is inactive and/or when the displacement actuator applies a constant load to the tissue, and/or from the data when the displacement actuator applies an increasing load on the tissue.

18. The system of claim 1, wherein the wave detector is at least one of an (ultra-) sound wave detector, a visual light spectrum 2D or 3D static picture camera, a visual light spectrum 2D or 3D moving picture camera, an infrared detector, an ultraviolet detector, a LIDAR, a radar, a microwave antenna.

19. The system of claim 18, wherein the camera is a CCD-camera.

20. The system of claim 18, wherein the wave detector is arranged to detect the position of the marker.

Description

BRIEF DESCRIPTION OF THE FIGURES

[0055] In the drawings:

[0056] FIG. 1 shows a basic layout of a system according to the present disclosure;

[0057] FIG. 2 shows a top view at the system of FIG. 1 during investigation; and

[0058] FIG. 3 shows a top view at the system of FIG. 1 during investigation of slightly deformed tissue caused by the presence of malignant cells.

[0059] Whenever in the figures the same reference numerals are applied, these numerals refer to the same parts.

DETAILED DESCRIPTION

[0060] FIG. 1 shows a basic layout of a system 1 of the invention for screening tissue 2 on the presence of malignant cells in said tissue 2. In the shown case the tissue is of a breast, although this is not essential. Instead of a breast also other tissue may be screened with the system and method of the invention on the occurrence of malignant cells.

[0061] The system 1 comprises a wave detector 3 and a data processing device 4 connected or connectable to the wave detector 3 for processing data received from the wave detector 3.

[0062] The system 1 further comprises an actuator 5 to mechanically excite the tissue 2 which is suspected to comprise malignant cells, and the processing device 4 comprises an analyzer 6 connected to the wave detector 3 for analyzing the data received from the wave detector 3 in response to the actuator 5 mechanically exciting the tissue 2. The analyzer 6 is arranged to identify and select the tissue 2′ which has in comparison with tissue 2″ that is not suspected to comprise malignant cells, an elevated probability to comprise malignant cells.

[0063] The choice of wave detector 3 that is used is dependent on the type of actuator 5 that is applied to mechanically excite the tissue 2. Mechanically exciting the tissue 2 may be done for instance with a sound emitter, an ultrasound emitter, a pulsed laser source (which is known to inflict ultrasound waves in tissue subjected to the pulsed laser source), or—as is shown in FIG. 1—with a mechanical displacement actuator 5. FIG. 1 also shows a supporting surface 11 against which the displacement actuator 5 presses the tissue 2 under investigation.

[0064] Corresponding to the type of actuator used, the wave detector 3 may be selected as one of an (ultra-) sound wave detector, a visual light spectrum 2D or 3D static picture camera, a visual light spectrum 2D or 3D moving picture camera, or even an infrared detector, an ultraviolet detector, a LIDAR, a radar, or a microwave antenna. When as is shown in FIG. 1, a camera is applied this preferably is a CCD-camera 3.

[0065] When the actuator is a displacement actuator 5 it must be arranged for displacing a tissue engaging surface or contact area 5′ of the displacement actuator 5 along a predetermined path and/or applying a predetermined load on the tissue 2 to be investigated. The resulting deformation of the tissue 2 can then be observed with the wave detector 3. Based thereon the analyzer 6 of the data processing device 4 determines from the data received from the wave detector 3 an estimated stiffness value of the tissue 2 under investigation, wherein the analyzer 6 is arranged to use this stiffness value as an indication for the presence or nonpresence of malignant cells.

[0066] A nonlimiting example that relates to the envisaged detection of malignant cells with the wave detector 3 is the following. For comparative purposes FIG. 3 differs from FIG. 2 to show that tissue 2 under investigation may behave differently depending on the location and nature of the presence of malignant cells 2′ in the tissue 2. In FIG. 2 the pressure applied to the tissue 2 homogeneously spreads through the tissue 2 under investigation, whereas in FIG. 3 there is an inhomogeneous spreading of the pressure applied to the tissue 2. This difference may serve as a visual indication which is detectable by the wave detector 3 that further investigation may be warranted as to the (non-)presence of malignant cells.

[0067] In a refined embodiment of the system 1 of the invention the analyzer 6 determines from the data received from the wave detector 3 local differences of estimated stiffness values of the tissue 2 under investigation, wherein the analyzer 6 is arranged to use these local differences of stiffness values as an indication for the presence or nonpresence of malignant cells. The local differences in stiffness value correspond to healthy tissue and tissue comprising malignant cells. The deformation of the tissue as shown in FIG. 3 is an indication of such local differences in stiffness value.

[0068] FIG. 1 further shows that the data processing device 4 comprises or connects to a data storage device 7 for storage of data received from the wave detector 3. This enables that the analyzer 6 can be equipped to operate on data received from the wave detector 3 and/or from the data storage device 7, wherein the data has different timestamps so as to enable a longitudinal comparison of data over time and to derive from this comparison an indication of the probable presence of malignant cells.

[0069] FIG. 1 depicts the situation that the tissue 2 under investigation is mechanically excited by a load applied by the displacement actuator 5 on the tissue 2. It is preferable however that the wave detector 3 is enabled to collect and provide data to the data processing device 4 from two different situations, notably one situation in which said data relates at least to the tissue 2 being disengaged and released from a load by the displacement actuator 5, and another situation in which the tissue 2 is being engaged and loaded by the displacement actuator 5, the latter preferably according to a predetermined trajectory until reaching a predetermined full load being applied to the tissue 2.

[0070] FIG. 1 further schematically shows that the displacement actuator 5 may be equipped with at least one marker 8 which enables position detection of the tissue engaging surface or contact area 5′ of the displacement actuator 5. The tissue engaging surface or contact area 5′ is also shown in the top view provided by FIG. 2. For the purpose of position detection of the tissue engaging surface or contact area 5′ it is preferred that the wave detector 3 is arranged to detect the position of the marker 8. Such a detectable marker 8 is preferably also provided on the supporting surface 11 against which the displacement actuator 5 presses the tissue 2 under investigation. This is shown in FIG. 1.

[0071] Most preferably the data collected and provided by the wave detector 3 to the data processing device 4 relates to a complete load-path-trajectory wherein the load provided by the displacement actuator 5 on the tissue 2 develops from no-load to the predetermined full load.

[0072] In certain embodiments it is useful that the displacement actuator 5 is equipped with a capacitive measurement organ (not shown) to determine the contact area 5′ (see FIG. 2) between the displacement actuator 5 and the tissue 2 during engagement of the tissue 2 by the displacement actuator 5. If such a capacitive measurement organ is not applied, the data processing device 4 can be equipped to estimate from the data the contact area between the displacement actuator 5 and the tissue 2 as it develops during engagement of the tissue 2 by the displacement actuator 5. In particular it may then be desirable that the analyzer 6 is arranged to derive an estimated stiffness value of the tissue 2 from the estimated or measured contact area 5′ between the displacement actuator 5 and the tissue 2 during engagement of the tissue 2 by the displacement actuator 5, or from a longitudinal comparison of the estimated or measured contact area 5′ developing over time and to derive from this comparison an indication of the presence of malignant cells. The reliability of the detection of malignant cells may be further improved by arranging that the estimation or measurement of the contact area 5′ between the displacement actuator 5 and the tissue 2 is monitored during a complete cycle of engaging and disengaging of the tissue 2 by the displacement actuator 5.

[0073] In another embodiment the analyzer 6 is arranged to derive an estimated stiffness value of the tissue 2 from a measured or calculated force applied to the tissue 2 by the displacement actuator 5 and the estimated or measured contact area 5′ between the displacement actuator 5 and the tissue 2 during engagement of the tissue 2 by the displacement actuator 5. More preferred is that the analyzer 6 is arranged to derive an estimated stiffness value of the tissue 2 from a longitudinal comparison of a measured or calculated force applied to the tissue 2 by the displacement actuator 5 over time, and the estimated or measured contact area 5′ developing over time between the displacement actuator 5 and the tissue 2 during engagement of the tissue 2 by the displacement actuator 5. In combination the force applied by the displacement actuator 5 and the estimated or measured contact area 5′, enables the calculation of an estimated or measured pressure applied to the tissue 2 which is a factor which can be taken into account in the estimation whether or not malignant cells are present in the tissue 2.

[0074] In still another embodiment the data processing device is equipped to determine from the data an estimated volume of the tissue being investigated. In this embodiment it is preferred that the data processing device 4 is equipped to determine from the data an estimated volume of the tissue 2 being investigated when the displacement actuator 5 is inactive and/or when the displacement actuator 5 applies a load on the tissue 2 and/or during a complete cycle of engaging and disengaging of the tissue 2 by the displacement actuator 5.

[0075] It is also possible to combine data and to arrange the analyzer 6 to derive an estimated stiffness value of the tissue 2 from a measured or calculated force applied to the tissue 2 and at least one of the estimated volume of the tissue 2, the contact area 5′ between the displacement actuator 5 and the tissue 2, and a projected area obtained from a projection of the volume of the tissue, one thing and another derived from the data when the displacement actuator 5 is inactive and/or when the displacement actuator 5 applies a constant load to the tissue 2, and/or from the data when the displacement actuator 5 applies an increasing load on the tissue 2. The term ‘projected area’ as used herein refers to a virtual contour projected in a line of sight from the detector to a supporting surface 11 against which the displacement actuator 5 presses the tissue 2 under investigation.

[0076] To improve accuracy the system 1 may be equipped with a position sensor 9 for measuring a position of a tissue engaging surface 5′ of the displacement actuator 5 and/or a force sensor 10 for measuring a force that the displacement actuator 5 provides to the tissue 2, which position sensor 9 and/or force sensor 10 are connected (not shown) to the data processing device 4 for use by the data processing device 4 in combination with the estimated or measured contact area 5′ between the displacement actuator 5 and the tissue 2 during engagement of the tissue 2 by the displacement actuator 5 so as to arrange that the load applied by the displacement actuator 5 to the tissue 2 is normalized to a pressure which the displacement actuator 5 applies to the tissue 2.

[0077] Although this is not essential to the invention, FIG. 1 shows that the system 1 processes data derived from a humans breast. Under circumstances it may be preferable that the system 1 is designed for processing data derived from a left breast and a right breast from a same patient, and to arrange that the analyzer 6 derives from differences between the left breast and the right breast an indication of malignant cells in one breast or in both breasts.

[0078] Embodiments of the present invention can include every combination of features that are disclosed herein independently from each other. Although the invention has been discussed in the foregoing with reference to an exemplary embodiment of the system and method of the invention, the invention is not restricted to this particular embodiment which can be varied in many ways without departing from the invention. The discussed exemplary embodiment shall therefore not be used to construe the appended claims strictly in accordance therewith. On the contrary the embodiment is merely intended to explain the wording of the appended claims without intent to limit the claims to this exemplary embodiment. The scope of protection of the invention shall therefore be construed in accordance with the appended claims only, wherein a possible ambiguity in the wording of the claims shall be resolved using this exemplary embodiment.

[0079] Variations and modifications of the present invention will be obvious to those skilled in the art and it is intended to cover in the appended claims all such modifications and equivalents. The entire disclosures of all references, applications, patents, and publications cited above are hereby incorporated by reference. Unless specifically stated as being “essential” above, none of the various components or the interrelationship thereof are essential to the operation of the invention. Rather, desirable results can be achieved by substituting various components and/or reconfiguration of their relationships with one another.

[0080] Optionally, embodiments of the present invention can include a general or specific purpose computer or distributed system programmed with computer software implementing steps described above, which computer software may be in any appropriate computer language, including but not limited to C++, FORTRAN, ALGOL, BASIC, Java, Python, Linux, assembly language, microcode, distributed programming languages, etc. The system may also include a plurality of such computers/distributed systems (e.g., connected over the Internet and/or one or more intranets) in a variety of hardware implementations. For example, data processing can be performed by an appropriately programmed microprocessor, computing cloud, Application Specific Integrated Circuit (ASIC), Field Programmable Gate Array (FPGA), or the like, in conjunction with appropriate memory, network, and bus elements. One or more processors and/or microcontrollers can operate via instructions of the computer code and the software is preferably stored on one or more tangible non-transitive memory-storage devices.