Abstract:
A method and device in accordance with the present invention enabling detecting mechanical and structural properties of the breast tissue that are indicative of breast cancer. Detection of nodules is achieved by placing the breast into a mechanical scanning unit comprising of a two-dimensional pressure sensor array and a mobile linear pressure sensor array located opposite to the two-dimensional pressure sensor array, and analyzing the signals from the pressure sensors. The device is able to objectively detect presence of lesions suspicious for cancer or other breast pathologies in the breast and provide means for computerized three-dimensional mechanical imaging of the breast.

Description:
[0001] This invention was made with government support under SBIR Grants No. 1 R43 CA65246-01 At and No. 2 R44 CA69175-03 awarded by the National Institutes of Health, National Cancer Institute. The government has certain rights in this invention. 
     
    
     
       BACKGROUND OF THE INVENTION  
         [0002]    1. Field of the Invention  
           [0003]    The present invention relates to a method and apparatus for the computerized mechanical palpation of the breast and detecting changes in mechanical properties of the breast tissue that are indicative of breast cancer and other breast pathologies accompanied by changes in the tissue viscoelasticity.  
           [0004]    2. Description of the Related Art  
           [0005]    Breast cancer is a major source of cancer morbidity and mortality in women. Various techniques have been developed for early diagnosis of breast cancer including ultrasonic imaging, nuclear magnetic resonance imaging, x-rays, and the like. Currently, the most widely used clinical method of diagnosing breast cancer is mammography. Efforts to reduce mortality via screening mammography have been successful with improvement in survival, particularly in women over 50 years old. One of the major disadvantages of the use of mammography is patients&#39; exposure to radiation.  
           [0006]    One of the safest and oldest techniques of detecting tissue disease is manual palpation. Palpation encompasses examination using the sense of touch, and is based on the significant difference in elasticity of normal and diseased tissues. Overall, about two-thirds of cancers are detected by palpation. Such sensitivity is related to significant changes in mechanical properties of tissues in the course of breast cancer development. In the United States the technique of self-palpation is widely taught to women as an effective means of early cancer detection. A significant fraction of breast cancer is first detected by women themselves who find suspicious lesions within their breasts and bring the problem to the attention of their physicians. The main disadvantage of manual palpation is its high degree of subjectivity. The examiner has to instinctively relate what he or she perceives by the finger to his or her previous experience. Moreover, a physician performing the examination cannot objectively record the state of the examined breast.  
           [0007]    A number of devices have been developed for detecting regions of hardening in the breast tissues. Several authors have proposed various devices for breast palpation using different types of force sensors, but all with limited success. For example, a device described by Gentle in Gentle CR, “Mammobarography: A Possible Method of Mass Breast Screening”, I. Biomed. Eng. 10, 124-126, 1988 was capable of detecting ‘lumps of 6 mm in diameter in breast phantoms but was unable to obtain any quantitative data on lumps in a human breast. Many of the proposed breast self examination means were related to simple non-computerized mechanical systems enhancing sense of touch such as apparatuses described in U.S. Pat. No. 5,572,995, U.S. Pat. No. 4,657,021, U.S. Pat. No. 4,793,354, and U.S. Pat. No. D348618.  
           [0008]    Various types of devices mimicking manual palpation for detecting breast tumors using different types of force sensors have been developed. For example, Frei et al., U.S. Pat. No. 4,250,894, describes an instrument which uses a number of piezoelectric strips pressed into the breast during the examination by a pressurizing unit which applies a given periodic or steady’ stress to the tissue beneath the strips.  
           [0009]    Another method and device for breast examination are described in the U.S. Pat. No. 5,883,634 and U.S. Pat. No. 5,989,199. The sensors used in this device are based on the force sensor array manufactured by Tekscan Inc., Boston, Mass. The array consists of conductive rows and columns whose intersecting points form sensing locations. A material, which changes its electrical resistance under applied force, separates the rows and columns. Thus, each intersection becomes a force sensor. Clinical data obtained using this device were published in February 1999 issue of the Oncology News International, in an article entitled “Electronic Palpation May Detect Breast Cancers”. The device showed an overall sensitivity of 92% (detecting 108 of 118 palpable and nonpalpable lesions) vs. 86% for the physician&#39;s exams (102 of 118 lesions). The device correctly detected all eight palpable cancers found in the study population and two of three non-palpable cancers.  
           [0010]    Conventional imaging modalities capable of detecting motion of a tissue subjected to an external force (such as ultrasound or MRI) use indirect means of evaluation for determining the elasticity of the tissues. One such approach is based on determining the relative stiffness or elasticity of the tissue by applying ultrasound imaging techniques while vibrating the tissue at low frequencies. See. e.g., K. I. Parker et al, U.S. Pat. No. 5,099,848; R. M. Lerner et al.,  Sono - Elasticity: Medical Elasticity Images Derived From Ultrasound Signals in Mechanically Vibrated Targets.  Acoustical Imaging, Vol. 16, 317 (1988); T. A. Krouskop et al.,  A Pulsed Doppler Ultrasonic  241,  Rehab. Res. Dev.  Vol. 24, 1 (1987); and Y. Yamakoshi et al.,  Ultrasonic Imaging of Internal Vibration of Soft Tissue Under Forced Vibration,  IEEE Transactions on Ultrasonics, Ferroelectrics, and Frequency Control, Vol. 7, No. 2, Page 45 (1990).  
           [0011]    Another method proposed for measuring and imaging tissue elasticity is described in Ophir etal., U.S. Pat. No&#39;s. 5,107,837, 5,293,870, 5,143,070 and 5,178,147. This method includes emitting ultrasonic waves into the tissue and detecting an echo sequence resulting from the ultrasonic wave pulse. The tissue is then compressed (or alternatively decompressed from a compressed state) along the path. During such compression a second pulse of ultrasonic waves is sent along the path into the tissue. The second echo sequence resulting from the second ultrasonic wave pulse is detected. Next, the differential displacement of the selected echo segments of the first and second echo sequences are measured. A selected echo segment of the echo sequence, i.e., reflected RF signal, corresponds to a particular echo source within the tissue along the beam axis of the transducer. Time shifts in the echo segment are examined to measure compressibility of various regions in the examined tissue.  
           [0012]    All presently available methods of palpatory assessment of the breast are inferior to manual palpation in sensitivity and specificity. Therefore, further development of screening techniques with greater sensitivity, specificity and accuracy is urgently warranted. It is desirable to provide computerized palpation of the breast which is capable of detecting breast lesions with sensitivity and spatial resolution exceeding that of manual palpation for use in early diagnostics of breast cancer.  
           [0013]    The invention will be more fully described by reference to the following drawings.  
         SUMMARY OF THE INVENTION  
         [0014]    The present invention provides a device and method for detection of abnormalities in tissues accompanied by the changes in their elasticity (such as those caused by cancer). The method is based on a computerized mechanical imaging referred to herein as CMI. The essence of CMI is the reconstruction of the internal structure of the soft tissues in a human body by measuring a dynamic or oscillatory stress pattern using an array of pressure sensors. The pattern of the dynamic mechanical stress and its changes as a function of applied pressure and time contain comprehensive information on the mechanical properties and geometry of the internal structures of the studied tissues.  
           [0015]    The CMI devices are applicable in those fields of medicine where palpation is proven to be a sensitive tool in detecting and monitoring diseases (including but not limited to the breast cancer.  
           [0016]    In a preferred embodiment, the apparatus for mechanical imaging of the breast comprises an electronically controlled mechanical scanning unit with a number of pressure transducers and an electronic unit for data acquisition, processing and displaying of images. The mechanical scanning unit includes a compression mechanism, three-dimensional positioning system, and local pressure source with a linear pressure sensor array opposing a two-dimensional pressure sensor array. The local pressure source is either a roller that is moved over the examined breast or, in an alternate embodiment, a linear pressure sensor array which can be moved in three dimensions. The electronic unit receives the pressure data from the pressure transducers and the position data from the positioning system and determines the mechanical structure of the breast.  
           [0017]    The apparatus of the current invention uses sensors based on piezoelectric films, such as piezopolymer polyvinylidene fluoride (PVDF) and comprises mechanical arrangements allowing increasing PVDF signal. The piezopolymer film provides inexpensive means for measuring mechanical forces by converting them into electrical signals.  
           [0018]    In the method of the present invention, the position data and pressure response data are acquired for translational and oscillation displacement overlaying the breast by periodic pressing or oscillating the linear pressure sensor array attached to the slider pressed against the breast. A pattern of pressure responses, pressure gradient responses, and spectral characteristic of pressure responses are determined and used for generating a mechanical image of the breast.  
           [0019]    The present invention utilizes the similar mechanical information as obtained by manual palpation conducted by a skilled physician but objectively and with higher sensitivity and accuracy. The essence of the proposed method and device is detection of tissue heterogeneity by measuring changes in the surface stress pattern using a force sensing array applied to the tissue in the oscillatory mode. Temporal and spatial changes of the spectral components and phase relationships of oscillatory signals from the sensors contain information on the mechanical properties and geometry of the internal structures of the breast. The device and method in accordance with the present invention enable the user to detect changes in the breast tissue that are indicative of cancer development.  
           [0020]    The present invention expands on teachings of inter-relation of mechanical heterogeneities in the tissue and respective changes in the measured stress patterns, and temporal and spatial derivatives of the oscillatory signals from the force sensors on the surface of the tissue. The present invention also expands on the teaching that the above relationship forms the basis for a method of detecting and quantifying tissue abnormalities.  
           [0021]    With the foregoing and other objects, advantages and features of the invention that will become hereinafter apparent, the nature of the invention may be more clearly understood by referencing to the following detailed description of the invention, the appended claims and the several views illustrated in the drawing. 
       
    
    
     BRIEF DESCRIPTION OF THE DRAWINGS  
       [0022]    [0022]FIG. 1 is a cross-sectional side view of an embodiment of a mechanical scanning unit used with the pressure sensor array during breast examination;  
         [0023]    [0023]FIG. 2 is a detailed cross-sectional view of the mechanical scanning unit shown in FIG. 1 with a linear pressure sensor array and a two-dimensional pressure sensor array;  
         [0024]    [0024]FIG. 3 is a detailed cross-sectional front view of the mechanical scanning unit shown in FIG. 1 for performing mechanical imaging of a breast in accordance with the present invention;  
         [0025]    [0025]FIG. 4 is a schematic view of an apparatus for performing mechanical imaging of a breast in accordance with the present invention;  
         [0026]    [0026]FIG. 5A is a schematic diagram of a model experiment on breast phantom with a hard nodule;  
         [0027]    [0027]FIG. 5B is a graphical representation of pressure signals for the linear pressure sensor array and the two-dimensional pressure sensor array shown in FIG. 2 obtained by the apparatus of FIG. 4 using the model experiment of FIG. 5A.  
         [0028]    [0028]FIG. 5C is a graphical representation of pressure signals for the linear pressure sensor array and the two-dimensional pressure sensor array shown in FIG. 3, obtained by the apparatus of FIG. 4 using the model experiment of FIG. 5A.  
         [0029]    [0029]FIG. 6 is a graphical representation of amplitude of the first harmonic, amplitude of the second harmonic and a phase shift of the first harmonic for the pressure signals from the linear pressure sensor array calculated from the experimental data of FIGS. 5A and 5B;  
         [0030]    [0030]FIG. 7A is a graphical representation of amplitude of the first harmonic for pressure signals from the two-dimensional pressure sensor array calculated from the experimental data of FIGS. 5A and 5B.  
         [0031]    [0031]FIG. 7B is a topographic representation of the data shown in FIG. 7A;  
         [0032]    [0032]FIG. 8A is a graphical representation of amplitude of the second harmonic for pressure signals from two-dimensional pressure sensor array calculated from the experimental data of FIGS. 5A and 5B;  
         [0033]    [0033]FIG. 8B is a topographic representation of the data shown in FIG. 8A;  
         [0034]    [0034]FIG. 9A is a graphical representation of a phase shift of the second harmonic for pressure signals from the two-dimensional pressure sensor array calculated from the experimental data of FIGS. 5A and 5B;  
         [0035]    [0035]FIG. 9B is a topographic representation of the data shown in FIG. 9A;  
         [0036]    [0036]FIG. 10A is a graphical representation of a combined gradient along a sensor line for pressure signals from the two-dimensional pressure sensor array calculated from the experimental data of shown in FIGS. 5A and 5B;  
         [0037]    [0037]FIG. 10B is a topographic representation of the data shown in FIG. 10A;  
         [0038]    [0038]FIG. 11 is a schematic diagram of an electronic unit for controlling mechanical scanning, data acquisition, processing and displaying mechanical images of the breast for the clinical apparatus shown in FIG. 4;  
         [0039]    [0039]FIG. 12 shows a flow chart representative of an algorithm for determining diagnostic information from the mechanical imaging data in accordance with the present invention.  
     
    
     DETAILED DESCRIPTION OF THE INVENTION  
       [0040]    References will be made in detail to a preferred embodiment of the invention, an example of which is illustrated in the accompanying drawings. Wherever possible, the same reference numerals will be used throughout the drawings and the description will refer to the same or similar parts.  
         [0041]    An embodiment of the invention shown in FIGS.  1 - 4  is a clinical device for imaging the mechanical structure of the examined breast and diagnosing diseases accompanied by changes in the elasticity of the breast tissue. A perspective of the use of a device for mechanical imaging of the breast  10  of the present invention during breast examination is shown in FIG. 1. The patient sits in a chair so that the examined breast  8  is located and loosely inserted into the breast aperture  11 . Such examination position allows the pectoral muscles to relax and the chest to expand into breast aperture  11  for greater access to the breast tissue adjacent to the chest wall. Inside breast aperture  11 , breast  8  is placed and compressed between holder  12  and mechanical scanning unit  13 . Holder  12  includes two-dimensional pressure sensor array  33  on an upper surface thereof. Mechanical scanning unit  13  includes linear pressure sensor array  14 . Pressure transducers of two-dimensional pressure sensor array  33  and linear pressure sensor array  14  generate signals, which vary depending on the force applied to the breast tissue.  
         [0042]    Device  10  also comprises an electronic unit (not shown), housing  19 , electric power supply (not shown), computer display  20  and control unit  141 . Revolving holder  16  is coupled to support  15 . Positioning base  17  is coupled to housing  19 . Revolving holder  16  is received in positioning base  17 . Revolving holder  16  received in positioning base  17  can be rotated for rotating support  15  to allow holder  12  and mechanical scanning unit  13  to rotate along the horizontal axis. Revolving holder  16  received in positioning base  17  can move up and down along frame  18  connected to housing  19 . The examination is monitored on computer display  20 . Control unit  141  is intended for controlling the examination process, data analysis and data displaying.  
         [0043]    [0043]FIG. 2 shows a detailed cross-sectional view of a portion of device  10  including compression mechanism, robotic positioning system of the scanning unit and pressure sensor elements. Breast  8  is positioned adjacent air bag  22 . Vertical linear actuator  21  and air bag  22  control the level of breast compression by means of elevating or lowering horizontal linear actuator  23  connected to slider (not shown) of vertical linear actuator  21  and by inflating air bag  22 . Air bag  22  is secured on support  27 . Support  27  is connected to horizontal linear actuator  23  by means of two corbels  28 . Support  27  can be substantially flat. Linear pressure sensor array  14  extends from airbag  22  and is used, measures the level of the breast compression.  
         [0044]    The robotic positioning system includes mechanical scanning unit  13  connected to slider  29  of horizontal linear actuator  23 , linear pressure sensor array  14  which can move horizontally along axis  24  and rotary actuator  41 , as shown in FIG. 4, for rotating rotation unit  25  relative to horizontal axis  26 . Rotation unit  25  has two positions. The first position of rotation unit  25  is shown in FIG. 2 with linear pressure sensor array  14  contacting breast  8 . This position is used for local examination of breast  8  in oscillation mode using back-and-forth motion of linear pressure sensor array  14  along axis  26 . The second position of rotation unit  25  has rotation unit  25  rotated clockwise 90 degrees as shown by arrow  30 . Roller  31  contacting breast  8  in the second position of rotation unit  25  is used for scanning the entire breast by means of linear motion of scanning unit  13  as shown by arrow  32 . Movement out of roller  31  acts as an additional dynamic pressure element. Two-dimensional pressure sensor array  33  is mounted in holder  12 , as shown in FIG. 3.  
         [0045]    Disposable polymer films covering the superior and inferior aspects of breast  8  from above and below are replaced after each examination. The surface of these films facing the dynamic pressure of the element (linear pressure sensor array  14  or the roller  31 ) is covered with lubricant to decrease friction while moving the pressure element over the breast.  
         [0046]    [0046]FIGS. 3 and 4 illustrate mechanical scanning unit  13  in detail. Rotation unit  25  comprises 5 rollers  31 ,  34 ,  35 ,  36 ,  37 . Each roller  31 ,  34 ,  35 ,  36  is supported by two bearings  46  (see FIG. 4) mounted into the corresponding side supports  42 . Linear motion of pressure sensor array  14  connected to slider  39  is accomplished by sliding slider  39  along guide axes  38 . Guide axes  38  are attached into side supports  42 . Motor  44  controls back-and- forth motion of slider  39 . The torque of motor  44  is transferred through gear wheels  45 , wheel  54  and belt  40  to slider  39 . Guide axes  38  are attached into side supports  42 . Motor  44  is mounted to side support  42  by means of motor holder  47 .  
         [0047]    Holder  12  mounts two dimensional pressure sensor array  33 , as shown in FIG. 3. Each pressure sensor of two-dimensional pressure sensor array  33  comprises flexible support  48  and PVDF film  49 . PVDF film  49  has a metallization on the top surface and flexible support  48  has metallization on the surface which is in contact with PVDF film  49  to collect the charge generated by PVDF film  49  and to transfer it to the electronic circuit. A force applied to sensing tip  50  causes flexible support  48  to flex. This flexion in turn creates high tangential forces in PVDF film  49 . A row of pressure sensors  51  forms linear array  52 . Linear array  52  can be part of the printed circuit board having electronic components  53  to process the signal generated by PVDF film  49 . Two-dimensional pressure sensor array  33  comprises several linear arrays  52  mounted in holder  12 .  
         [0048]    Referring to FIG. 4, the three-dimensional space motion of linear pressure sensor array  14  is accomplished with vertical linear actuator  21 , horizontal linear actuator  23  connected to slider  55  of vertical linear actuator  21 , and linear pressure sensor array  14  connected to slider  56  of the actuator  23 . Connective pipe  57  extends from support  27  for air supply into airbag  22 . Cable  58  provides an electrical connection of linear pressure sensor array  14 . Cable  58  can be a flat flexible cable.  
         [0049]    [0049]FIG. 5A illustrates linear pressure sensor array  14  pressed against a tissue phantom  59  with a hard inclusion  60 . Oscillating linear pressure sensor array  14  over tissue phantom  59  enables detecting the hidden nodules and evaluating parameters for example: the diameter, hardness and depth. Frames  61  and  62 , shown respectively in FIG. 5B and FIG. 5C, are the graphical representation of the temporal dependence of signals  63  from linear pressure sensor array  14  as well as temporal dependence of signals  64  from one row of sensors of two-dimensional pressure sensor array  33  during oscillation of the respective linear pressure sensor array. The difference in time profiles of signals from the sensors located at different positions with regard to the nodule, as seen in records  61  and  62 , allows detecting and evaluating parameters of the nodules.  
         [0050]    [0050]FIG. 6 is a graphical representation of the amplitude of first harmonic  65 , amplitude of second harmonic  67  and of phase shift  66  for data of frame  61 , shown in FIG. SB. Presence of the nodule produces two distinctly expressed peaks  68  and  69 . Parameters M 10 , M 12 , M 21 , N 1 , A 1 , and B 1  can be used for tissue characterization in order to find all parameters of hard inclusion.  
         [0051]    [0051]FIG. 7A is a 3D graphical representation of the amplitude of first harmonic  71  for pressure signals from two-dimensional pressure sensor array  33  shown in FIG. 3 for the data of frame  62  shown in FIG. 5C. Hard inclusion is located between two peaks  72  and  73 . The peak amplitudes M 13  and distance between them A 2  characterize the inclusion.  
         [0052]    [0052]FIG. 7B is a topographic representation  74  with lines of equal level  75  for the data shown in FIG. 7A.  
         [0053]    [0053]FIG. 8A is a 3D graphical representation of the amplitude of second harmonic  81  for pressure signals from the two-dimensional pressure sensor array  33  shown in FIG. 3 for the data shown in FIG. 5C. The inclusion is located under peak  82 . Two additional peaks  83  with smaller amplitude may arise in the vicinity of peak  82 . The peak amplitude M 23  characterizes the inclusion. FIG. 8B is a topographic representation  84  with lines of equal level  85  for the data shown in FIG. 8A.  
         [0054]    [0054]FIG. 9A is a 3D graphical representation of a phase shift of second harmonic  91  for pressure signals from the two-dimensional pressure sensor array  33  shown in FIG. 3 for the data given in FIG. 5C. The inclusion is located close to a characteristic peak  92 . Additional peak  93  may arise in the vicinity of peak  92 . FIG. 9B is a topographic representation  94  with lines of equal level  95  for the data shown in FIG. 9A.  
         [0055]    [0055]FIG. 10A is a 3D graphical representation of a combined gradient  101  along a sensor line  52  for pressure signals from the two-dimensional pressure sensor array shown in FIG. 5C. The inclusion is located under a peak  102 . This procedure produces a higher signal/noise ratio and the nodule is detected without any ambiguity. FIG. 10B is a topographic representation  94  with lines of equal level  103  for the data shown in FIG. 10A.  
         [0056]    [0056]FIG. 11 is a schematic diagram of a preferred embodiment of electronic unit  109  for providing acquisition, scanning, processing and displaying the breast mechanical imaging data for the device shown in FIG. 1. A plurality of transducer elements  110  form pressure sensor array  14  of device  10 . A plurality of transducer elements  111  form two-dimensional pressure sensor array  33  of device  10 . Pressure sensing circuit  113  is formed of several amplifiers  114  to enhance respective signals generated by pressure transducer elements  110  and  111 , for detecting the forces applied to each transducer element  110  of pressure sensor array  14  and each transducer element  111  of pressure sensor array  33 . The amplified signals from amplifiers  114  are applied to multiplexer  115 . Multiplexed signals are converted to digital signals by the analog-to-digital converter  116  and are fed to processor  117 . Robotic 3D positioning system  112  includes linear actuators  21 ,  23  and rotation actuator  45  connected through controller  119  to processor  117 . Controller  120  is connected to processor  117  and controls air pressure in airbag  22 . Processor  117  is used to provide all required robotic manipulations of mechanical  13  scanning unit, to control the breast compression and position of each pressure sensing transducer  110 , to synchronize and filtrate pressure data received from linear pressure sensor array  14  and two-dimensional pressure array  33 . Processor  117  is also used for analysis of mechanical images of the breast, for delineating geometrical features and mechanical composition of the breast, such as lesions, nodules, stiffer tissue, and the like and for synthesis of the breast image, as described in the method illustrated in FIG. 12. Computer display  20  connected to processor  117  displays the process of breast examination and the results of the examination. Control unit  141  is connected to processor  117  for controlling the breast examination, data analysis and data display. Processor  117  communicates with analog-to-digital converter  116  and multiplexer  115  for sending data and control signals. A storage unit  118  is used for storing the results of the breast examination generated by the processor  117  and communication with the patient&#39;s database.  
         [0057]    [0057]FIG. 12 shows a flow chart representative of the preferred method and algorithm for analysis of information obtained by scanning the breast. Force data  121  from pressure sensor array  14  and data  122  from pressure sensor array  33  are acquired in real-time. Analog signals representing the force measured from all the force transducers of pressure sensor array  14  at the time t form force data  123  represented by A(p i ,n i ,t), where p i  is the pressure signal from of the pressure transducer n i . Analog signals representing the force measured from all the force transducers of two-dimensional pressure sensor array  33  at the time t form force data  124  represented by B(pj,nj;t}, where pj is the pressure signal from the pressure transducer n j . In block  125  the acquired force data  123  and force data  124  are combined over a period of time to conduct synchronization and filtration. In box  125  data are processed by one of the known approximation and filtration method, as described for example by J.- L. Stark, F. Murtagh and A. Bijaouiet,  Image Processing and Data Analysis.  Cambridge University Press (1998). In block  126 , corrected data is determined for correcting displacement and shifting of the breast during examination and correcting noise of various origins. Pressure field data is calculated by processing the transformed data to minimize noise and extract the 3D spatial distribution of pressure approximating ideal conditions of measurement. In block  127 , spectral analysis is used to analyze the data. In block  128 , spatial and temporal derivatives are used to analyze the data. The phase correlations, spectral composition of the signals, and spatial and temporal derivatives of the signals are evaluated and forwarded to the block  129  for evaluating mechanical and geometrical features of the breast. In block  130 , a pattern of pressure gradient responses is determined from force sensor array data. Various methods may be used to determine the pressure gradient responses grad{P(x,y,z)}. One method is calculating partial derivatives for a given pattern of pressure responses along array  52  to locate areas of hardness in the breast. Having approximated surfaces of equal pressure one can calculate geometrical parameters and hardness of the breast in local regions. In block  131  a breast image is synthesized from the data generated in the block  129 . The breast examination and the synthesized image of the breast are displayed on computer display  20 .  
         [0058]    Although certain presently preferred embodiments of the present invention have been specifically described herein, it will be apparent to those skilled in the art to which the invention pertains that variations and modifications of the various embodiments shown and described herein may be made without departing from the spirit and scope of the invention. Accordingly, it is intended that the invention be limited only to the extent required by the appended claims and the applicable rules of law.