EP0955887A1 - Ultrasound scanning - Google Patents

Ultrasound scanning

Info

Publication number
EP0955887A1
EP0955887A1 EP97945961A EP97945961A EP0955887A1 EP 0955887 A1 EP0955887 A1 EP 0955887A1 EP 97945961 A EP97945961 A EP 97945961A EP 97945961 A EP97945961 A EP 97945961A EP 0955887 A1 EP0955887 A1 EP 0955887A1
Authority
EP
European Patent Office
Prior art keywords
signal
radio frequency
imaging apparatus
ultrasonic imaging
identified
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
EP97945961A
Other languages
German (de)
French (fr)
Inventor
Gill Imp. College Science Tech. Medicine HEART
Richard I. Imp College Science Tech. Med KITNEY
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Imperial College of Science Technology and Medicine
Original Assignee
Imperial College of Science Technology and Medicine
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Imperial College of Science Technology and Medicine filed Critical Imperial College of Science Technology and Medicine
Publication of EP0955887A1 publication Critical patent/EP0955887A1/en
Withdrawn legal-status Critical Current

Links

Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B8/00Diagnosis using ultrasonic, sonic or infrasonic waves
    • A61B8/08Detecting organic movements or changes, e.g. tumours, cysts, swellings
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01SRADIO DIRECTION-FINDING; RADIO NAVIGATION; DETERMINING DISTANCE OR VELOCITY BY USE OF RADIO WAVES; LOCATING OR PRESENCE-DETECTING BY USE OF THE REFLECTION OR RERADIATION OF RADIO WAVES; ANALOGOUS ARRANGEMENTS USING OTHER WAVES
    • G01S7/00Details of systems according to groups G01S13/00, G01S15/00, G01S17/00
    • G01S7/52Details of systems according to groups G01S13/00, G01S15/00, G01S17/00 of systems according to group G01S15/00
    • G01S7/52017Details of systems according to groups G01S13/00, G01S15/00, G01S17/00 of systems according to group G01S15/00 particularly adapted to short-range imaging
    • G01S7/52023Details of receivers
    • G01S7/52036Details of receivers using analysis of echo signal for target characterisation
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01SRADIO DIRECTION-FINDING; RADIO NAVIGATION; DETERMINING DISTANCE OR VELOCITY BY USE OF RADIO WAVES; LOCATING OR PRESENCE-DETECTING BY USE OF THE REFLECTION OR RERADIATION OF RADIO WAVES; ANALOGOUS ARRANGEMENTS USING OTHER WAVES
    • G01S7/00Details of systems according to groups G01S13/00, G01S15/00, G01S17/00
    • G01S7/52Details of systems according to groups G01S13/00, G01S15/00, G01S17/00 of systems according to group G01S15/00
    • G01S7/52017Details of systems according to groups G01S13/00, G01S15/00, G01S17/00 of systems according to group G01S15/00 particularly adapted to short-range imaging
    • G01S7/52053Display arrangements
    • G01S7/52057Cathode ray tube displays
    • G01S7/52071Multicolour displays; using colour coding; Optimising colour or information content in displays, e.g. parametric imaging
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01SRADIO DIRECTION-FINDING; RADIO NAVIGATION; DETERMINING DISTANCE OR VELOCITY BY USE OF RADIO WAVES; LOCATING OR PRESENCE-DETECTING BY USE OF THE REFLECTION OR RERADIATION OF RADIO WAVES; ANALOGOUS ARRANGEMENTS USING OTHER WAVES
    • G01S15/00Systems using the reflection or reradiation of acoustic waves, e.g. sonar systems
    • G01S15/88Sonar systems specially adapted for specific applications
    • G01S15/89Sonar systems specially adapted for specific applications for mapping or imaging
    • G01S15/8906Short-range imaging systems; Acoustic microscope systems using pulse-echo techniques
    • G01S15/8979Combined Doppler and pulse-echo imaging systems
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01SRADIO DIRECTION-FINDING; RADIO NAVIGATION; DETERMINING DISTANCE OR VELOCITY BY USE OF RADIO WAVES; LOCATING OR PRESENCE-DETECTING BY USE OF THE REFLECTION OR RERADIATION OF RADIO WAVES; ANALOGOUS ARRANGEMENTS USING OTHER WAVES
    • G01S7/00Details of systems according to groups G01S13/00, G01S15/00, G01S17/00
    • G01S7/52Details of systems according to groups G01S13/00, G01S15/00, G01S17/00 of systems according to group G01S15/00
    • G01S7/52017Details of systems according to groups G01S13/00, G01S15/00, G01S17/00 of systems according to group G01S15/00 particularly adapted to short-range imaging
    • G01S7/52023Details of receivers
    • G01S7/52025Details of receivers for pulse systems
    • G01S7/52026Extracting wanted echo signals

Definitions

  • This invention relates to the field of ultrasound scanning. More particularly, this invention relates to the ultrasound scanning of biological tissue in medical applications.
  • Ultrasound scanning of biological tissue is a widely used diagnostic technique in medicine. Ultrasound scanning is non-invasive, quick, has a very low risk to the subject and requires comparatively inexpensive equipment compared to other scanning techniques.
  • An example of the use of ultrasound scanning is in the examination of blood vessel walls for the detection and characterisation of atherosclerosis.
  • Ultrasound scanning may be used to produce transverse or longitudinal cross sectional grey-scale images of blood vessels to identify plaques in the blood vessel walls.
  • Ultrasound B-mode grey-scale images can be difficult to interpret and in order to assist in this, and to try and obtain a more quantative assessment of the degree of severity of the plaques, blood flow measuring techniques using ultrasound scanning have been developed.
  • An example of this is colour flow mapping that uses Doppler effects to detect the speed of flow of blood through the lumen of a blood vessel. If constrictions/plaque are present in the blood vessel wall, then these tend to disturb the uniform blood flow (e.g. lead to downstream turbulence in the blood flow) that may be more readily identified using colour flow mapping techniques and quantified using Doppler techniques.
  • the plaques within blood vessels can be considered to fall into a number of different characteristic types.
  • a first type is a constriction in the lumen of the blood vessel formed by a fibrous thickening in the vessel wall. Such fibrous thickenings are of a relatively low risk rupture since they are unlikely to break free or lead to thrombosis.
  • Another type of plaque is one in which the thickening contains a calcified region that is relatively hard and brittle. Such calcified regions are thought to present a risk of cracking that in turn may lead to tissue damage of the blood vessel wall, haemorrhage and thrombosis generation. Perhaps the most dangerous type of plaque is a lipid plaque.
  • a lipid plaque within a thickened blood vessel wall consists of a pocket of fatty tissue that is held in place by a fibrous covering (cap). If the fibrous covering ruptures under stress (or for other reasons), then the lipid material is released into the blood flow with potential harmful consequences and the ruptured fibrous cap can itself lead to potential thrombosis. During the healing process a blood clot will form around the ruptured area with the potential for causing emboli or blocking the vessel. It will be seen that thickening of a blood vessel wall can be the result of differing plaque types with very differing risk levels associated with them. These differing risk levels have the result that different treatments are appropriate. However, with an ultrasound scanner, whilst the constriction of the blood vessel and the thickened blood vessel wall may be identified, it is very much more difficult to identify which type of plaque is present. This difficulty is particularly severe between a fibrous plaque and a lipid plaque.
  • the present invention provides an ultrasonic imaging apparatus for imaging biological tissue, said ultrasonic imaging apparatus comprising: an ultrasonic transducer for emitting ultrasonic sound energy into biological tissue to be imaged and for generating radio frequency signals from received reflected ultrasonic sound energy; and a signal processor for comparing said radio frequency signals with predetermined signal parameters indicative of different types of biological tissue histology to identify one or more regions of different histology and for generating a histological image that visually distinguishes said one or more regions of different histology.
  • the present invention takes a different approach to the analysis of the signals generated by an ultrasound scan.
  • the invention recognises that rather than merely using the radio frequency signals from the reflective ultrasonic sound energy to generate grey-scale images (of ever increasing resolution and frame rate), the radio frequency signals contain information embedded within themselves that with careful analysis can reveal histological characteristics of the tissue being scanned. This is not a true histological image in terms of a microscope slide, but is an image that gives and indication of the histological characteristics of the tissue. This histological information is in many cases very much more valuable than any increase in resolution or frame rate.
  • the radio frequency signals may be compared by a signal processor with predetermined signal parameters (e.g.
  • the invention may be used to distinguish between normal tissue, lipid plaques, fibrous plaques and calcified plaques within a blood vessel wall.
  • the invention could also be used in the scanning of other biological tissues, e.g. mammography, liver scanning, kidney scanning etc.
  • the histological image that is produced by the present invention can be displayed independently.
  • said signal processor generates a grey-scale image of said biological tissue based upon said radio frequency signal intensity, said grey-scale image being overlain with said histological image.
  • Overlying the histological image with the grey-scale image allows the information contained within each to mutually support one another for diagnostic purposes in confirming interpretation of the results of the scan.
  • the histological image is a colour image with different colours representing different tissue histology or homogeneity.
  • the present invention may be utilised in the examination of biological tissue of many different types.
  • the invention is particularly suited for use in systems in which said biological tissue is an in vivo blood vessel and said regions of different histology include different types of vessel wall plaque.
  • the signal processor should operate such that a lumen area of an in vivo blood vessel is identified by searching said radio frequency signals for a contiguous region having a signal peak to trough value below a predetermined lumen amplitude threshold and a signal peak value below a predetermined lumen level threshold.
  • the lumen area search starts from a known point that may be either manually or automatically identified as being within the lumen area. This identification may use or be assisted by ultrasonic blood flow detection.
  • a preferred technique for identifying a lipid plaque is one of searching said radio frequency signals outside of a lumen area for a contiguous area having a signal peak to trough value above a predetermined noise amplitude threshold and below a predetermined lipid plaque amplitude threshold, a signal peak value below a predetermined lipid plaque level threshold, and the presence of a fibrous cap.
  • a preferred technique for identifying a calcified plaque is one of searching said radio frequency signals outside of a lumen area for a contiguous area having a signal peak value above a predetermined calcified plaque peak level threshold, a signal trough value below a predetermined calcified plaque trough level threshold, a variation in signal peak to trough value below a predetermined calcified plaque amplitude variation threshold and a variation in signal period below a predetermined calcified plaque period variation threshold.
  • a further histological characteristic that may be diagnostically useful can be derived in embodiments in which said signal processor calculates from variations in parameters characterising said radio frequency signals a homogeneity value indicative of the degree of tissue homogeneity within one or more regions of said histological image and controls display within said histological image of said one or more regions for which a homogeneity value was calculated to visually represent said calculated homogeneity value.
  • the homogeneity value is only calculated for those regions not already identified as lumen, lipid plaque or calcified plaque. Fibrous plaques shown as a thickened vessel wall area with a high homogeneity value that is not otherwise identified as a vessel wall plaque.
  • said signal processor divides said radio frequency signal into signal areas, at least some signal areas being tested to identify biological tissue histology by reference to their own signal characteristics in combination with signal characteristics of surrounding signal areas. It will be appreciated that the present invention could be embodied as an addon device to an existing ultrasound scanner that has a radio frequency signal and control signal output port that allows access to the radio frequency signals generated by reflected ultrasonic sound energy.
  • the present invention provides an ultrasonic imaging apparatus for imaging biological tissue using radio frequency signals generated from reflected ultrasonic sound energy, said ultrasonic imaging apparatus comprising: a signal processor for comparing said radio frequency signals with predetermined signal parameters indicative of different types of biological tissue histology to identify one or more regions of different histology and for generating a histological image that visually distinguishes said one or more regions of different histology.
  • the present invention provides an ultrasonic imaging method of imaging biological tissue, said ultrasonic imaging method comprising the steps of: emitting ultrasonic sound energy into biological tissue to be imaged; generating radio frequency signals from received reflected ultrasonic sound energy; comparing said radio frequency signals with predetermined signal parameters indicative of different types of biological tissue histology to identify one or more regions of different histology; and generating a histological image that visually distinguishes said one or more regions of different histology.
  • Figure 1 schematically illustrates an ultrasonic scanning apparatus for scanning blood vessels
  • Figure 2 schematically illustrates a grey-scale image of a blood vessel suffering from a constriction due to vessel wall thickening by a plaque of an unknown type
  • Figure 3 illustrates a radio frequency signal along a scan line path through the vessel of Figure 2 with characteristics indicative of a lipid plaque
  • Figure 4 illustrates a radio frequency signal as in Figure 3 but this time with characteristics indicative of a calcified plaque
  • Figure 4 illustrates a radio frequency signal as in Figure 3 but this time with characteristics indicative of a fibrous plaque
  • FIG. 6 illustrates the sequence of operations of the signal processing portion of the system of Figure 1;
  • Figure 7 illustrates the histological analysis strategy of the technique set out in Figure 6.
  • FIG. 1 illustrates an ultrasonic scanning apparatus that comprises a conventional ultrasound scanner 2 (e.g. a Sonus 2500 produced by Hewlett Packard) that has an ultrasonic transducer 4 (of a known frequency) that may be used to investigate a blood vessel 6 within the thoracic cavity 8 of a patient.
  • the ultrasound scanner has a radio frequency signal output port that allows access to the raw radio frequency signal data for each scan line. Together with the radio frequency signal scan lines (similar to the raster scan input to a television receiver) there are separate synchronising signals.
  • the radio frequency signal is supplied via an amplifier stage to a high speed analogue to digital converter 10 which digitises the signal under control of control signal from a control unit and stores it in a buffer memory before passing it to a workstation computer 12 where the digitised radio frequency signal data for a complete signal frame is stored within the RAM of the workstation computer 12.
  • this digitised data may be manipulated therein under software control and the workstation computer functions as a signal processing apparatus. It will be appreciated that the functionality of the analogue to digital converter 10 and the workstation computer 12 could be incorporated within the ultrasound scanner 2 itself to form an integral unit if desired or could be embodied as a separate stand alone device.
  • Figure 2 illustrates an example grey-scale image of a blood vessel.
  • the blood vessel wall has a thickened portion 14.
  • the lumen 16 may be manually identified by the operator possibly with the assistance of blood flow mapping techniques or maybe automatically identified (e.g. use colour flow mapping to identify a point having the highest velocity blood flow providing this information is passed to the workstation). Whilst the thickened portion 14 of the blood vessel wall is clearly a plaque of some form, it is sometimes difficult for the operator to unambiguously identify which type of plaque is shown.
  • FIG 3 illustrates the blood vessel of Figure 2 and the radio frequency signal produced along a scan line A, B, C, D, E and F through the blood vessel.
  • the plaque is a lipid plaque.
  • the unthickened blood vessel wall A, B produces a strong and relatively irregular series of echoes in the radio frequency signal. This is followed by a low amplitude portion corresponding to the reflection from the blood within the lumen 16.
  • the fibrous cap of the lipid plaque shows as a narrow area of relatively strong reflection C, D.
  • the lipid body has the characteristic of relatively low reflection in the portion D, E.
  • the final portion is the outer wall E, F.
  • the lumen 16 has already been identified by the user and so the portion B, C of the radio frequency signal is already identified and accounted for. In this way, the low amplitude reflection from the lumen is not confused with low amplitude reflection from lipid.
  • the portion D, E has peak to trough values (amplitude) above a noise level but below a predetermined threshold characteristic of a lipid plaque and the absolute value of the peaks is below a threshold indicative of lipid plaques.
  • the portion D, E can be identified as corresponding to a lipid plaque and corresponding portions in adjacent scan lines may be identified to form a contiguous area within the histological image.
  • the remaining regions are searched for calcified plaques (as described below) and then subject to a determination of a homogeneity value that is equal to the product of the variance of the peak values and the variance of the peak to trough values. This homogeneity value is then mapped to a corresponding colour range of a colour palette.
  • the lipid region has its own distinctive colour within the colour palette.
  • the threshold values used in the lipid plaque test and other tests are specific to a particular ultrasound scanner and power setting being used. Lookup tables of threshold scaling factors for different power settings may be held within the signal processor and the scanner can undergo calibration to further improve the reliability of the thresholds used. Whilst the absolute values of the thresholds may be scanner and setup specific, the relative values of the threshold are much less so and together provide a good indicator of tissue histology. The threshold values can be indexed to a single value from a lookup table.
  • Figure 4 corresponds to Figure 3 except in this case the region D, E contains a calcified plaque.
  • the characteristic signal parameters of a calcified plaque are strong and regular echoes. These characteristics may be identified by searching outside of the lumen for a continuous area having signal peak values above a given threshold, signal trough values below a given threshold and a variation in peak to trough values below a threshold in conjunction with a variation in signal period below a threshold. These signal parameters in combination define a highly regular and high amplitude signal. When such a calcified plaque region has been identified it is assigned its own distinctive colour within the histological image and is excluded from calculations of the homogeneity value.
  • Figure 5 is similar to Figure 3 except in this case the plaque is fibrous and the area D, E contains fibrous tissue.
  • the area D, E does not meet either of the test criteria that identify a lipid plaque or a calcified plaque and so is not identified as either of these types. Accordingly, the area D, E is subject to the calculation of a homogeneity value together with the portions A, B; C, D and E, F.
  • Figure 6 illustrates the sequence of operation of the signal processor. At step
  • the signal processor captures a single frame of data (post time gain compensation processing) at its maximum dynamic range and reconstructs a grey-scale image.
  • the user examines a corresponding grey-scale image of the frame and identifies one point within the lumen.
  • the signal processor floods out the lumen area and marks it as lumen by searching away from the identified point until the signal value exceeds a given amplitude threshold indicative of the lumen wall being reached. Scan lines adjacent to the scan line containing the identified point can be searched starting from a point corresponding in distance from the ultrasonic transducer to the identified point.
  • the user identifies the outer edges of the vessel by tracing around these in the reconstructed grey-scale image using a pointing device such as a mouse. Identifying the outer portion of the blood vessel is relatively straight forward to an experienced operator. The outer edges of the vessel are used to terminate the subsequent searches for structures and the calculation of the homogeneity value.
  • those areas outside of the lumen but within the inside edges of the user defined contour are searched for areas (e.g. four signal cycles area treated as an area of sufficient size to be worthy of giving significance to its characteristics) for parameters indicative of lipid histology. If such areas are found, then they are marked within the radio frequency signal data as well as being excluded from further evaluation.
  • areas e.g. four signal cycles area treated as an area of sufficient size to be worthy of giving significance to its characteristics
  • a search is carried out for calcified structures and these areas are similarly marked.
  • all the remaining areas within the image that are not lumen, lipid core areas or calcified areas are subject to the calculation of a homogeneity value of which the logarithm is taken and then this value used to index a palette of a range of colours. Fibrous tissue is associated with low homogeneity values.
  • the histographic images displayed with lipid areas and calcified areas marked in their own distinctive colours and the colours dependent upon the homogeneity value calculated are displayed for the other areas. The lumen is left dark or is assigned its own colour.
  • Figure 7 illustrates the sequence of operations of Figure 6 in relation to an individual radio frequency scan line.
  • the lumen portion B, C is identified by searching away from the given point to find the position at which the signal value exceeds a predetermined threshold. This area is then marked as lumen and excluded from further searches.
  • the second search is conducted through all areas other than the lumen and is looking for signals characteristic of lipid histology. In this case, such signals are found in the region D, E and this region is marked accordingly and excluded from further searching.
  • the third stage is a search for calcified histology signal parameters through all the remaining areas that have not already been marked. In this case, no such characteristic signals were identified. Finally, all the remaining areas are subject to a homogeneity value calculation and marked with a colour value derived from this homogeneity value.

Landscapes

  • Engineering & Computer Science (AREA)
  • Physics & Mathematics (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Computer Networks & Wireless Communication (AREA)
  • General Physics & Mathematics (AREA)
  • Radar, Positioning & Navigation (AREA)
  • Remote Sensing (AREA)
  • Pathology (AREA)
  • Molecular Biology (AREA)
  • Biophysics (AREA)
  • Radiology & Medical Imaging (AREA)
  • Biomedical Technology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Medical Informatics (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Surgery (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Ultra Sonic Daignosis Equipment (AREA)

Abstract

An ultrasound scanning technique for biological tissue examines the radio frequency signals derived from reflected ultrasonic energy to identify signal parameters indicative of particular tissue histology. Such identification is then used to produce a histological image of the biological tissue. The technique is particularly useful in the examination of blood vessels to identify different types of plaque within the vessel wall. Lipid plaques produce relatively low levels of reflection. Calcified plaques produce high levels of regular reflection. Fibrous plaques may be identified as a highly homogeneous thickened wall area that does not show the characteristics of a lipid plaque. A homogeneity value for the radio frequency signal is calculated for all areas not identified as lipid plaques or calcified plaques and then this homogeneity value is mapped to a colour that is displayed within the histological image.

Description

ULTRASOUND SCANNING
This invention relates to the field of ultrasound scanning. More particularly, this invention relates to the ultrasound scanning of biological tissue in medical applications.
Ultrasound scanning of biological tissue is a widely used diagnostic technique in medicine. Ultrasound scanning is non-invasive, quick, has a very low risk to the subject and requires comparatively inexpensive equipment compared to other scanning techniques. An example of the use of ultrasound scanning is in the examination of blood vessel walls for the detection and characterisation of atherosclerosis.
Diseased blood vessel walls are a major cause of illness. As well as constricting the blood flow, diseased blood vessel walls can release or cause the production of emboli that can become lodged elsewhere completely blocking the blood supply to certain body organs and causing clinical problems such as strokes. Ultrasound scanning may be used to produce transverse or longitudinal cross sectional grey-scale images of blood vessels to identify plaques in the blood vessel walls.
Ultrasound B-mode grey-scale images can be difficult to interpret and in order to assist in this, and to try and obtain a more quantative assessment of the degree of severity of the plaques, blood flow measuring techniques using ultrasound scanning have been developed. An example of this is colour flow mapping that uses Doppler effects to detect the speed of flow of blood through the lumen of a blood vessel. If constrictions/plaque are present in the blood vessel wall, then these tend to disturb the uniform blood flow (e.g. lead to downstream turbulence in the blood flow) that may be more readily identified using colour flow mapping techniques and quantified using Doppler techniques.
Current development effort in ultrasound scanning apparatus and methods for use in such diagnosis is primarily directed toward increasing the frame rate of the image generated by the ultrasound scanner in order to produce a real time smoothly moving representation of the image and the blood flow within that vessel. While such efforts do improve the diagnosis, they suffer from a number of inherent and significant problems.
The plaques within blood vessels can be considered to fall into a number of different characteristic types. A first type is a constriction in the lumen of the blood vessel formed by a fibrous thickening in the vessel wall. Such fibrous thickenings are of a relatively low risk rupture since they are unlikely to break free or lead to thrombosis. Another type of plaque is one in which the thickening contains a calcified region that is relatively hard and brittle. Such calcified regions are thought to present a risk of cracking that in turn may lead to tissue damage of the blood vessel wall, haemorrhage and thrombosis generation. Perhaps the most dangerous type of plaque is a lipid plaque. A lipid plaque within a thickened blood vessel wall consists of a pocket of fatty tissue that is held in place by a fibrous covering (cap). If the fibrous covering ruptures under stress (or for other reasons), then the lipid material is released into the blood flow with potential harmful consequences and the ruptured fibrous cap can itself lead to potential thrombosis. During the healing process a blood clot will form around the ruptured area with the potential for causing emboli or blocking the vessel. It will be seen that thickening of a blood vessel wall can be the result of differing plaque types with very differing risk levels associated with them. These differing risk levels have the result that different treatments are appropriate. However, with an ultrasound scanner, whilst the constriction of the blood vessel and the thickened blood vessel wall may be identified, it is very much more difficult to identify which type of plaque is present. This difficulty is particularly severe between a fibrous plaque and a lipid plaque.
Viewed from one aspect the present invention provides an ultrasonic imaging apparatus for imaging biological tissue, said ultrasonic imaging apparatus comprising: an ultrasonic transducer for emitting ultrasonic sound energy into biological tissue to be imaged and for generating radio frequency signals from received reflected ultrasonic sound energy; and a signal processor for comparing said radio frequency signals with predetermined signal parameters indicative of different types of biological tissue histology to identify one or more regions of different histology and for generating a histological image that visually distinguishes said one or more regions of different histology.
The present invention takes a different approach to the analysis of the signals generated by an ultrasound scan. The invention recognises that rather than merely using the radio frequency signals from the reflective ultrasonic sound energy to generate grey-scale images (of ever increasing resolution and frame rate), the radio frequency signals contain information embedded within themselves that with careful analysis can reveal histological characteristics of the tissue being scanned. This is not a true histological image in terms of a microscope slide, but is an image that gives and indication of the histological characteristics of the tissue. This histological information is in many cases very much more valuable than any increase in resolution or frame rate. More particularly, the radio frequency signals may be compared by a signal processor with predetermined signal parameters (e.g. amplitude characteristics, peak or trough level characteristics, variance characteristics, phase irregularity characteristics etc) that individually or collectively, and sometimes in combination with characteristics from surrounding areas, identify particular tissue histology. In the above example, the invention may be used to distinguish between normal tissue, lipid plaques, fibrous plaques and calcified plaques within a blood vessel wall. The invention could also be used in the scanning of other biological tissues, e.g. mammography, liver scanning, kidney scanning etc.
The histological image that is produced by the present invention can be displayed independently. However, in preferred embodiments of the invention said signal processor generates a grey-scale image of said biological tissue based upon said radio frequency signal intensity, said grey-scale image being overlain with said histological image.
Overlying the histological image with the grey-scale image allows the information contained within each to mutually support one another for diagnostic purposes in confirming interpretation of the results of the scan.
Interpretation of the histological image is made easier in embodiments of the invention in which said histological image is a colour image with different colours representing different tissue histology or homogeneity. As mentioned before, the present invention may be utilised in the examination of biological tissue of many different types. However, the invention is particularly suited for use in systems in which said biological tissue is an in vivo blood vessel and said regions of different histology include different types of vessel wall plaque.
Within such blood vessel analysis it is found convenient that the signal processor should operate such that a lumen area of an in vivo blood vessel is identified by searching said radio frequency signals for a contiguous region having a signal peak to trough value below a predetermined lumen amplitude threshold and a signal peak value below a predetermined lumen level threshold.
The lumen area search starts from a known point that may be either manually or automatically identified as being within the lumen area. This identification may use or be assisted by ultrasonic blood flow detection. A preferred technique for identifying a lipid plaque is one of searching said radio frequency signals outside of a lumen area for a contiguous area having a signal peak to trough value above a predetermined noise amplitude threshold and below a predetermined lipid plaque amplitude threshold, a signal peak value below a predetermined lipid plaque level threshold, and the presence of a fibrous cap. A preferred technique for identifying a calcified plaque is one of searching said radio frequency signals outside of a lumen area for a contiguous area having a signal peak value above a predetermined calcified plaque peak level threshold, a signal trough value below a predetermined calcified plaque trough level threshold, a variation in signal peak to trough value below a predetermined calcified plaque amplitude variation threshold and a variation in signal period below a predetermined calcified plaque period variation threshold.
A further histological characteristic that may be diagnostically useful can be derived in embodiments in which said signal processor calculates from variations in parameters characterising said radio frequency signals a homogeneity value indicative of the degree of tissue homogeneity within one or more regions of said histological image and controls display within said histological image of said one or more regions for which a homogeneity value was calculated to visually represent said calculated homogeneity value.
In preferred embodiments the homogeneity value is only calculated for those regions not already identified as lumen, lipid plaque or calcified plaque. Fibrous plaques shown as a thickened vessel wall area with a high homogeneity value that is not otherwise identified as a vessel wall plaque. In order to more reliably identify tissue histology said signal processor divides said radio frequency signal into signal areas, at least some signal areas being tested to identify biological tissue histology by reference to their own signal characteristics in combination with signal characteristics of surrounding signal areas. It will be appreciated that the present invention could be embodied as an addon device to an existing ultrasound scanner that has a radio frequency signal and control signal output port that allows access to the radio frequency signals generated by reflected ultrasonic sound energy. Accordingly, viewed from another aspect the present invention provides an ultrasonic imaging apparatus for imaging biological tissue using radio frequency signals generated from reflected ultrasonic sound energy, said ultrasonic imaging apparatus comprising: a signal processor for comparing said radio frequency signals with predetermined signal parameters indicative of different types of biological tissue histology to identify one or more regions of different histology and for generating a histological image that visually distinguishes said one or more regions of different histology.
Viewed from a further aspect the present invention provides an ultrasonic imaging method of imaging biological tissue, said ultrasonic imaging method comprising the steps of: emitting ultrasonic sound energy into biological tissue to be imaged; generating radio frequency signals from received reflected ultrasonic sound energy; comparing said radio frequency signals with predetermined signal parameters indicative of different types of biological tissue histology to identify one or more regions of different histology; and generating a histological image that visually distinguishes said one or more regions of different histology.
An embodiment of the invention will now be described, by way of example only, with reference to the accompanying drawings in which: Figure 1 schematically illustrates an ultrasonic scanning apparatus for scanning blood vessels;
Figure 2 schematically illustrates a grey-scale image of a blood vessel suffering from a constriction due to vessel wall thickening by a plaque of an unknown type;
Figure 3 illustrates a radio frequency signal along a scan line path through the vessel of Figure 2 with characteristics indicative of a lipid plaque; Figure 4 illustrates a radio frequency signal as in Figure 3 but this time with characteristics indicative of a calcified plaque;
Figure 4 illustrates a radio frequency signal as in Figure 3 but this time with characteristics indicative of a fibrous plaque;
Figure 6 illustrates the sequence of operations of the signal processing portion of the system of Figure 1;
Figure 7 illustrates the histological analysis strategy of the technique set out in Figure 6.
Figure 1 illustrates an ultrasonic scanning apparatus that comprises a conventional ultrasound scanner 2 (e.g. a Sonus 2500 produced by Hewlett Packard) that has an ultrasonic transducer 4 (of a known frequency) that may be used to investigate a blood vessel 6 within the thoracic cavity 8 of a patient. The ultrasound scanner has a radio frequency signal output port that allows access to the raw radio frequency signal data for each scan line. Together with the radio frequency signal scan lines (similar to the raster scan input to a television receiver) there are separate synchronising signals.
The radio frequency signal is supplied via an amplifier stage to a high speed analogue to digital converter 10 which digitises the signal under control of control signal from a control unit and stores it in a buffer memory before passing it to a workstation computer 12 where the digitised radio frequency signal data for a complete signal frame is stored within the RAM of the workstation computer 12.
Once this digitised data has been captured by the workstation computer 12, it may be manipulated therein under software control and the workstation computer functions as a signal processing apparatus. It will be appreciated that the functionality of the analogue to digital converter 10 and the workstation computer 12 could be incorporated within the ultrasound scanner 2 itself to form an integral unit if desired or could be embodied as a separate stand alone device.
Figure 2 illustrates an example grey-scale image of a blood vessel. The blood vessel wall has a thickened portion 14. The lumen 16 may be manually identified by the operator possibly with the assistance of blood flow mapping techniques or maybe automatically identified (e.g. use colour flow mapping to identify a point having the highest velocity blood flow providing this information is passed to the workstation). Whilst the thickened portion 14 of the blood vessel wall is clearly a plaque of some form, it is sometimes difficult for the operator to unambiguously identify which type of plaque is shown.
Figure 3 illustrates the blood vessel of Figure 2 and the radio frequency signal produced along a scan line A, B, C, D, E and F through the blood vessel. In this case the plaque is a lipid plaque. The unthickened blood vessel wall A, B produces a strong and relatively irregular series of echoes in the radio frequency signal. This is followed by a low amplitude portion corresponding to the reflection from the blood within the lumen 16. The fibrous cap of the lipid plaque shows as a narrow area of relatively strong reflection C, D. The lipid body has the characteristic of relatively low reflection in the portion D, E. The final portion is the outer wall E, F.
In practice, the lumen 16 has already been identified by the user and so the portion B, C of the radio frequency signal is already identified and accounted for. In this way, the low amplitude reflection from the lumen is not confused with low amplitude reflection from lipid. As the rest of the radio frequency signal along the scan line is searched the portion D, E has peak to trough values (amplitude) above a noise level but below a predetermined threshold characteristic of a lipid plaque and the absolute value of the peaks is below a threshold indicative of lipid plaques. In this way, the portion D, E can be identified as corresponding to a lipid plaque and corresponding portions in adjacent scan lines may be identified to form a contiguous area within the histological image. Once the lumen and the lipid portion of the scan line have been identified the remaining regions are searched for calcified plaques (as described below) and then subject to a determination of a homogeneity value that is equal to the product of the variance of the peak values and the variance of the peak to trough values. This homogeneity value is then mapped to a corresponding colour range of a colour palette. The lipid region has its own distinctive colour within the colour palette.
It will be appreciated that the threshold values used in the lipid plaque test and other tests are specific to a particular ultrasound scanner and power setting being used. Lookup tables of threshold scaling factors for different power settings may be held within the signal processor and the scanner can undergo calibration to further improve the reliability of the thresholds used. Whilst the absolute values of the thresholds may be scanner and setup specific, the relative values of the threshold are much less so and together provide a good indicator of tissue histology. The threshold values can be indexed to a single value from a lookup table.
Figure 4 corresponds to Figure 3 except in this case the region D, E contains a calcified plaque. The characteristic signal parameters of a calcified plaque are strong and regular echoes. These characteristics may be identified by searching outside of the lumen for a continuous area having signal peak values above a given threshold, signal trough values below a given threshold and a variation in peak to trough values below a threshold in conjunction with a variation in signal period below a threshold. These signal parameters in combination define a highly regular and high amplitude signal. When such a calcified plaque region has been identified it is assigned its own distinctive colour within the histological image and is excluded from calculations of the homogeneity value.
Finally, Figure 5 is similar to Figure 3 except in this case the plaque is fibrous and the area D, E contains fibrous tissue. The area D, E does not meet either of the test criteria that identify a lipid plaque or a calcified plaque and so is not identified as either of these types. Accordingly, the area D, E is subject to the calculation of a homogeneity value together with the portions A, B; C, D and E, F. Thus, in the histological image the thickening will be seen as a relatively homogeneous portion of vessel wall that does not contain any lipid or calcified areas. Figure 6 illustrates the sequence of operation of the signal processor. At step
18 the signal processor captures a single frame of data (post time gain compensation processing) at its maximum dynamic range and reconstructs a grey-scale image. At step 20 the user examines a corresponding grey-scale image of the frame and identifies one point within the lumen. At step 22 the signal processor floods out the lumen area and marks it as lumen by searching away from the identified point until the signal value exceeds a given amplitude threshold indicative of the lumen wall being reached. Scan lines adjacent to the scan line containing the identified point can be searched starting from a point corresponding in distance from the ultrasonic transducer to the identified point.
At step 24 the user identifies the outer edges of the vessel by tracing around these in the reconstructed grey-scale image using a pointing device such as a mouse. Identifying the outer portion of the blood vessel is relatively straight forward to an experienced operator. The outer edges of the vessel are used to terminate the subsequent searches for structures and the calculation of the homogeneity value.
At step 26 those areas outside of the lumen but within the inside edges of the user defined contour are searched for areas (e.g. four signal cycles area treated as an area of sufficient size to be worthy of giving significance to its characteristics) for parameters indicative of lipid histology. If such areas are found, then they are marked within the radio frequency signal data as well as being excluded from further evaluation.
At step 28 a search is carried out for calcified structures and these areas are similarly marked. At step 30 all the remaining areas within the image that are not lumen, lipid core areas or calcified areas are subject to the calculation of a homogeneity value of which the logarithm is taken and then this value used to index a palette of a range of colours. Fibrous tissue is associated with low homogeneity values. At step 32 the histographic images displayed with lipid areas and calcified areas marked in their own distinctive colours and the colours dependent upon the homogeneity value calculated are displayed for the other areas. The lumen is left dark or is assigned its own colour.
Figure 7 illustrates the sequence of operations of Figure 6 in relation to an individual radio frequency scan line. Firstly, the lumen portion B, C is identified by searching away from the given point to find the position at which the signal value exceeds a predetermined threshold. This area is then marked as lumen and excluded from further searches. The second search is conducted through all areas other than the lumen and is looking for signals characteristic of lipid histology. In this case, such signals are found in the region D, E and this region is marked accordingly and excluded from further searching. The third stage is a search for calcified histology signal parameters through all the remaining areas that have not already been marked. In this case, no such characteristic signals were identified. Finally, all the remaining areas are subject to a homogeneity value calculation and marked with a colour value derived from this homogeneity value.

Claims

1. An ultrasonic imaging apparatus for imaging biological tissue, said ultrasonic imaging apparatus comprising: an ultrasonic transducer for emitting ultrasonic sound energy into biological tissue to be imaged and for generating radio frequency signals from received reflected ultrasonic sound energy; and a signal processor for comparing said radio frequency signals with predetermined signal parameters indicative of different types of biological tissue histology to identify one or more regions of different histology and for generating a histological image that visually distinguishes said one or more regions of different histology.
2. An ultrasonic imaging apparatus as claimed in claims 1, wherein said signal processor generates a grey-scale image of said biological tissue based upon said radio frequency signal intensity, said grey-scale image being overlain with said histological image.
3. An ultrasonic imaging apparatus as claimed in claim 2, wherein said histological image is a colour image with different colours representing different tissue histology or homogeneity.
4. An ultrasonic imaging apparatus as claimed in any one of claims 1, 2 and 3, wherein said biological tissue is an in vivo blood vessel and said regions of different histology include normal tissue and different types of vessel wall plaques.
5. An ultrasonic imaging apparatus as claimed in claim 4, wherein a lumen area of an in vivo blood vessel is identified by searching said radio frequency signals for a contiguous region having a signal peak to trough value below a predetermined lumen amplitude threshold and a signal peak value below a predetermined lumen level threshold.
6. An ultrasonic imaging apparatus as claimed in claim 5, wherein said lumen area search starts from a known point identified as being within said lumen area.
7. An ultrasonic imaging apparatus as claimed in claim 6, wherein said known point is identified using ultrasonic blood flow detection.
8. An ultrasonic imaging apparatus as claimed in claim 4, wherein a lumen area of an in vivo blood vessel is identified by ultrasonic blood flow mapping.
9. An ultrasonic imaging apparatus as claimed in claim 4, wherein a lumen area of an in vivo blood vessel is identified by user input.
10. An ultrasonic imaging apparatus as claimed in claim 4, wherein an outer border of an in vivo blood vessel is identified by user input.
11. An ultrasonic imaging apparatus as claimed in any one of claims 4 to 10, wherein a lipid plaque area is identified by searching said radio frequency signals outside of a lumen area for a contiguous area having a signal peak to trough value above a predetermined noise amplitude threshold and below a predetermined lipid plaque amplitude threshold, a signal peak value below a predetermined lipid plaque level threshold and the presence of a fibrous cap.
12. An ultrasonic imaging apparatus as claimed in any one of claims 4 to 11, wherein a calcified plaque area is identified by searching said radio frequency signals outside of a lumen area for a contiguous area having a signal peak value above a predetermined calcified plaque peak level threshold, a signal trough value below a predetermined calcified plaque trough level threshold, a variation in signal peak to trough value below a predetermined calcified plaque amplitude variation threshold and a variation in signal period below a predetermined calcified plaque period variation threshold.
13. An ultrasonic imaging apparatus as claimed in any one of claims 4 to 12, wherein said signal processor calculates from variations in parameters characterising said radio frequency signals a homogeneity value indicative of the degree of tissue homogeneity within one or more regions of said histological image and controls display within said histological image of said one or more regions for which a homogeneity value was calculated to visually represent said calculated homogeneity value.
14. An ultrasonic imaging apparatus as claimed in claim 13, wherein said homogeneity value is calculated for regions not identified as lumen, lipid plaque or calcified plaque.
15. An ultrasonic imaging apparatus as claimed in any one of the preceding claims, wherein said signal processor divides said radio frequency signal into signal areas, at least some signal areas being tested to identify biological tissue histology by reference to their own signal characteristics in combination with signal characteristics of surrounding signal areas.
16. An ultrasonic imaging apparatus for imaging biological tissue using radio frequency signals generated from reflected ultrasonic sound energy, said ultrasonic imaging apparatus comprising: a signal processor for comparing said radio frequency signals with predetermined signal parameters indicative of different types of biological tissue histology to identify one or more regions of different histology and for generating a histological image that visually distinguishes said one or more regions of different histology.
17. An ultrasonic imaging method of imaging biological tissue, said ultrasonic imaging method comprising the steps of: emitting ultrasonic sound energy into biological tissue to be imaged; generating radio frequency signals from received reflected ultrasonic sound energy; comparing said radio frequency signals with predetermined signal parameters indicative of different types of biological tissue histology to identify one or more regions of different histology; and generating a histological image that visually distinguishes said one or more regions of different histology.
EP97945961A 1996-11-29 1997-11-27 Ultrasound scanning Withdrawn EP0955887A1 (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
GB9624970A GB2319841A (en) 1996-11-29 1996-11-29 Ultrasound scanning of tissue
GB9624970 1996-11-29
PCT/GB1997/003259 WO1998023210A1 (en) 1996-11-29 1997-11-27 Ultrasound scanning

Publications (1)

Publication Number Publication Date
EP0955887A1 true EP0955887A1 (en) 1999-11-17

Family

ID=10803754

Family Applications (1)

Application Number Title Priority Date Filing Date
EP97945961A Withdrawn EP0955887A1 (en) 1996-11-29 1997-11-27 Ultrasound scanning

Country Status (8)

Country Link
EP (1) EP0955887A1 (en)
JP (1) JP2001509043A (en)
CN (1) CN1245408A (en)
AU (1) AU5128398A (en)
CA (1) CA2272917A1 (en)
GB (1) GB2319841A (en)
IL (1) IL130118A0 (en)
WO (1) WO1998023210A1 (en)

Families Citing this family (17)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6120445A (en) 1998-10-02 2000-09-19 Scimed Life Systems, Inc. Method and apparatus for adaptive cross-sectional area computation of IVUS objects using their statistical signatures
US6200268B1 (en) 1999-09-10 2001-03-13 The Cleveland Clinic Foundation Vascular plaque characterization
US7727153B2 (en) * 2003-04-07 2010-06-01 Sonosite, Inc. Ultrasonic blood vessel measurement apparatus and method
JP4263943B2 (en) 2003-05-07 2009-05-13 テルモ株式会社 Ultrasonic diagnostic equipment
WO2005034759A1 (en) * 2003-10-09 2005-04-21 Juridical Foundation Osaka Industrial Promotion Organization Lumen wall tissue state evaluation device, image processing device, image processing method and computer program
US20070129625A1 (en) * 2005-11-21 2007-06-07 Boston Scientific Scimed Systems, Inc. Systems and methods for detecting the presence of abnormalities in a medical image
JP4839446B2 (en) * 2007-02-27 2011-12-21 国立大学法人山口大学 Ultrasound diagnostic apparatus and tissue characterization program
JP4787358B2 (en) * 2007-04-27 2011-10-05 株式会社日立メディコ Ultrasonic diagnostic equipment
US8545412B2 (en) 2009-05-29 2013-10-01 Boston Scientific Scimed, Inc. Systems and methods for making and using image-guided intravascular and endocardial therapy systems
JP5412242B2 (en) * 2009-11-05 2014-02-12 伸治 久米 Ultrasonic tomographic image processing device
US8715187B2 (en) * 2010-12-17 2014-05-06 General Electric Company Systems and methods for automatically identifying and segmenting different tissue types in ultrasound images
JP5886581B2 (en) * 2011-09-26 2016-03-16 公立大学法人大阪府立大学 Vascular plaque diagnostic imaging system
WO2014210430A1 (en) 2013-06-27 2014-12-31 Tractus Corporation Systems and methods for tissue mapping
KR102347038B1 (en) 2014-11-06 2022-01-04 삼성메디슨 주식회사 Ultra sonic apparatus and method for scanning thereof
KR102490069B1 (en) * 2015-08-18 2023-01-19 삼성메디슨 주식회사 Ultrasonic diagnostic apparatus and operating method for the same
CN107875518A (en) * 2017-12-20 2018-04-06 深圳冲激波科技有限公司 A kind of radio frequency physiotherapy equipment and its control method
CN114631848B (en) * 2022-02-14 2024-04-05 逸超医疗科技(北京)有限公司 Method, device, equipment and storage medium for detecting tissue uniformity

Family Cites Families (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4509368A (en) * 1981-06-22 1985-04-09 The Commonwealth Of Australia Ultrasound tomography
US4858124A (en) * 1984-08-15 1989-08-15 Riverside Research Institute Method for enhancement of ultrasonic image data
US4917097A (en) * 1987-10-27 1990-04-17 Endosonics Corporation Apparatus and method for imaging small cavities
US4945478A (en) * 1987-11-06 1990-07-31 Center For Innovative Technology Noninvasive medical imaging system and method for the identification and 3-D display of atherosclerosis and the like
US5845639A (en) * 1990-08-10 1998-12-08 Board Of Regents Of The University Of Washington Optical imaging methods
US5203337A (en) * 1991-05-08 1993-04-20 Brigham And Women's Hospital, Inc. Coronary artery imaging system
US5360005A (en) * 1992-01-10 1994-11-01 Wilk Peter J Medical diagnosis device for sensing cardiac activity and blood flow
US5417215A (en) * 1994-02-04 1995-05-23 Long Island Jewish Medical Center Method of tissue characterization by ultrasound
US5535750A (en) * 1994-09-30 1996-07-16 Kabushiki Kaisha Ishikawa Seisakusho, Ltd. Method and apparatus for evaluating the progress of osteoporosis by ultrasonic signals

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO9823210A1 *

Also Published As

Publication number Publication date
GB9624970D0 (en) 1997-01-15
WO1998023210A1 (en) 1998-06-04
AU5128398A (en) 1998-06-22
CN1245408A (en) 2000-02-23
CA2272917A1 (en) 1998-06-04
GB2319841A (en) 1998-06-03
JP2001509043A (en) 2001-07-10
IL130118A0 (en) 2000-06-01

Similar Documents

Publication Publication Date Title
US6200268B1 (en) Vascular plaque characterization
US5628322A (en) Method of ultrasound imaging and diagnostic ultrasound system
Urbani et al. In vivo radiofrequency-based ultrasonic tissue characterization of the atherosclerotic plaque.
EP0955887A1 (en) Ultrasound scanning
EP1599122B1 (en) Non-invasive plaque characterization system
Foster et al. The ultrasound macroscope: initial studies of breast tissue
US5601086A (en) Beat frequency ultrasonic microsphere contrast agent detection system
US8162836B2 (en) System and method for characterizing tissue based upon split spectrum analysis of backscattered ultrasound
JP4068234B2 (en) Ultrasonic diagnostic equipment
WO2002100249A2 (en) Apparatus and method for ultrasonically identifying vulnerable plaque
JP2003061964A (en) Ultrasonic diagnostic apparatus
US5419332A (en) Mapping of flow parameters
Spencer et al. Characterisation of atherosclerotic plaque by spectral analysis of intravascular ultrasound: an in vitro methodology
JPH11327A (en) Ultrasonograph
US6652460B2 (en) Method for ultrasonic imaging, particularly of moving bodies, such as surgical utensils, tissues, flows, or the like
US20050273010A1 (en) Method and system for ultrasound contrast-imaging
WO2014200417A1 (en) Method and system for determining a property of a non-homogeneous material
US5313946A (en) Method and apparatus for the characterization of tissue or other structure
Jafarpisheh et al. Evaluation of contrast to noise ratio of parametric images of regularized estimates of quantitative ultrasound
JPH08336527A (en) Ultrasonic diagnostic system
Thomson et al. Effect of Freezing and fixation on quantitative ultrasound parameters in phantoms of brain and brain tumour
Landini et al. Quantitative ultrasonic imaging of the atherosclerotic plaque: in vitro and preliminary in vivo findings
Jones et al. Detection of early fatty plaque using quantitative ultrasound methods
Nicholas et al. Quantitative image analysis for diffuse liver disease
Yigiter et al. In-vivo estimates of attenuation in atherosclerotic plaque and thrombus using a PC-based data acquisition system

Legal Events

Date Code Title Description
PUAI Public reference made under article 153(3) epc to a published international application that has entered the european phase

Free format text: ORIGINAL CODE: 0009012

17P Request for examination filed

Effective date: 19990628

AK Designated contracting states

Kind code of ref document: A1

Designated state(s): AT BE CH DE DK ES FI FR GB GR IE IT LI LU MC NL PT SE

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: THE APPLICATION IS DEEMED TO BE WITHDRAWN

18D Application deemed to be withdrawn

Effective date: 20010601