Patent Publication Number: US-2021177375-A1

Title: Image-Based Diagnostic Systems

Description:
FIELD OF THE INVENTION 
     The present invention relates to systems for analysing medical images, for example of the heart, and for measuring parameters of the imaged subject. It has application in echocardiography, but also with other imaging modalities such as X-ray computer tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography (PET). 
     BACKGROUND TO THE INVENTION 
     Echocardiography is widely used as a method of imaging the heart. It uses a series of rapidly acquired pulse-echo ultrasound images to build up, for example, a real time video image of the heart. The images are typically two dimensional (2D) and the images are typically analysed visually by a skilled clinician, although computer analysis of the images is known, for example from U.S. Pat. No. 8,077,944. In stress echocardiography, the heart is imaged in a rest condition, i.e. when the subject is at rest, and under a stress condition, for example after exercise. The function of the heart in the two conditions can be compared to provide information on how it responds to stress. If it is not appropriate for the subject to be exercised, then stress can be induced or simulated, for example by injecting a stimulant such as dobutamine into the subject. Dobutamine stress echo (DSE) is widely used in diagnosing coronary artery disease (CAD). 
     SUMMARY OF THE INVENTION 
     The present invention provides a system for measuring deformation of the heart, for example for diagnosing a heart condition, the system comprising an imaging system arranged to acquire two images of the heart at respective points in the cardiac cycle. The system may comprise locating means for locating a series of pairs of points on the images, each pair of points indicating the respective positions of a single part of the heart in the two images. The system may comprise processing means arranged to calculate, for example from the positions of said pairs of points, a value of at least one parameter of the deformation of the heart. 
     The processing means may be arranged to compare the value of at least one parameter with reference data to generate a diagnostic output. 
     The at least one parameter may include any one or more of: a displacement in at least one direction of a part of the heart; a mean, for all of said parts of the heart, of the displacements in at least one direction; the sum of displacements in two different directions, for example the longitudinal and radial directions, for at least one of said parts of the heart; the mean, for all of said parts of the heart, of that sum of displacements; and the principle transformation which is described in more detail below. 
     The locating means may comprise a user input device arranged to enable a user to locate said pairs of points in the images and to record the positions of said pairs of points, for example by recording the coordinates of each of the points in a two dimensional coordinate system. 
     The imaging system may be arranged to store the images as respective image data sets, and the locating means may be arranged to process the image data sets to determine the locations of said pairs of points and to record the positions of said pairs of points. 
     The at least one parameter may comprise a plurality of parameters and the processing means may be arranged to compare the value of each of the parameters with a respective reference value. 
     The system may be arranged to acquire a further set of two images of the heart at respective points in a cardiac cycle, with heart in a second condition, which is different from its condition when the first set of two images are acquired. For example one of the conditions may be a rest condition when the subject is at rest and one of the conditions may be a stress condition when the subject is under stress. Each of the parameters may be determined once for each set of images. One or more further parameters may be defined which combine data from the two sets of images. For example the difference in the value of one of the parameters, between the two sets of images, may be used as a further parameter. 
     The processing means may be arranged to define a decision tree for generating the diagnostic output from the values of the parameters. The decision tree may include a plurality of decision points. Each decision point may define a reference value of one of the parameters. For example one of the decision points may define a reference value of the principal transformation, and/or one of the decision points may define a value of the shear transformation as described in more detail below, and/or one of the decision points may define a reference value of the difference between the principal transformation in the two different conditions of the heart. Systems for building decision trees from training data are well known, such as C4.5 and J48. 
     The invention further provides a method of measuring deformation of the heart, for example for diagnosing a heart condition, the method comprising acquiring two images of the heart at respective points in the cardiac cycle, locating a series of pairs of points on the images, each pair of points indicating the respective positions of a single part of the heart in the two images. The method may further comprise calculating, for example from the positions of said pairs of points, at least one parameter of the deformation of the heart. The method may further comprise comparing the at least one parameter with reference data to generate a diagnostic output. 
     The invention further provides a method of producing a system for diagnosing a heart condition, the method including analysing a set of images, wherein each of the images has a diagnostic outcome associated with it, the method including calculating a value of the at least one parameter for each of the images, analysing the values and the diagnostic outcomes to determine a relationship or correlation between the two. 
     The method may further comprise using machine learning to develop a decision tree for generating the diagnostic output from the values of the parameters. The method may be performed on a computer system or processor system, which may form part of an imaging system, or may comprise a separate computer. 
     The diagnostic output may relate to a variety of cardiac conditions, such as coronary artery disease (CAD), or mitral regurgitation, or hypertrophic cardiomyopathy. 
     The imaging system may comprise an echocardiography system, or it may be an X-ray imaging system such as an X-ray computer tomography (CT) scanner, magnetic resonance imaging (MRI) scanner, or a positron emission tomography (PET) scanner. 
     The system or method may further comprise, in any workable combination, any one or more features or steps of the preferred embodiments of the invention, as will now be described with reference to the accompanying drawings. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         FIG. 1  is a schematic view of a system according to an embodiment of the invention; 
         FIG. 2  shows schematically a four chamber view of a heart; 
         FIG. 3  is a flow diagram showing the main steps of a diagnostic method performed by the system of  FIG. 1 ; 
         FIG. 4  is a schematic view of a comparison of two images performed by the system of  FIG. 1 ; 
         FIGS. 5 a  and 5 b    show a sample image at two stages of the analysis as performed by the system of  FIG. 1 ; 
         FIGS. 6 a  and 6 b    show the results of analysis of sample data obtained using the system of Figure; and 
         FIG. 7  is a flow diagram showing the algorithm used to produce the results of  FIGS. 6 a    and  6   b.    
     
    
    
     DESCRIPTION OF THE PREFERRED EMBODIMENTS 
     Referring to  FIG. 1 , an echocardiography system  100  comprises a transducer array  102  arranged to be located close to the body of the patient  104 , typically as close to the heart as possible, a processing unit  106  which includes a processor  108  which may be a digital electronic processor, a memory  110  such as a hard disk, and a display  112 , such as a flat screen monitor or LED display. The system may further include a user input device, for example a touchscreen  114  integrated into the display  112 , which provides a user input allowing a user to provide inputs to the system  100 . Other user inputs such as a mouse, touchpad or keyboard may of course be used. The processor unit  106  is connected to the transducer array  102  and is arranged to control the transducer array as a phased array so as to emit an ultrasound beam which scans across the patient in a series of pulses, and detect reflected ultrasound from the heart from each pulse. One scan of the heart builds up a single image, and the scan is repeated at typically 25 to 50 images per second to build up a real time video image of the heart showing its movement during the cardiac cycle. Each image may be stored in the memory  110  as an image data set which may comprise, for example, intensity values for each of the pixels of which the image is made up. 
     While the system is described in general terms above, suitable echocardiography systems include, for example the Philips Epic iE33, GE vivid e9, or portable systems such as the Philips CX50, or hand held systems. 
     The process of echocardiography is well known and will not be described in detail. There are several different imaging methods, but two dimensional imaging may be used. It is known to provide images on several different planes through the heart, which show different aspects of the four main chambers of the heart, the left ventricle (LV), right ventricle (RV), left atrium (LA) and right atrium (RA). Such views include, for example, an apical four chamber view, apical two or three chamber views and parasternal long and short axis views. In each case, while a single still image can be obtained, typically a series of views is acquired over the cycle of the heart so that its movement can be recorded and analysed. 
     Referring to  FIG. 2 , if the images are four chamber apical views, they show a 2D plane of the heart  200  showing the left ventricle  202 , the right ventricle  204 , the left atrium  206  and the right atrium  208 . The plane includes the long axis  210  of the LV, also extends through the apex  212  of the LV, the lateral wall  214  of the LV and the septum  216 . 
     Referring to  FIG. 3 , the echocardiography system  100  may be arranged to acquire at step  300  a sequence of 2D images and store them in its memory  110 . The images may be acquired over a single cardiac cycle, and may include for example between ten and 50 images covering one cycle. The acquisition of the images can of course be carried out on a conventional echocardiography system  100 . The following analysis of the images can be carried out using the same processing unit  106  that forms part of the echocardiography system as shown in  FIG. 1 . However the images may be downloaded onto a computer, such as a laptop or PC, which has a processor, memory, user input and display, which operate for this purpose in the same way as those of the control unit  106 , and the further analysis of the images may be carried out on that computer under the control of dedicated software. 
     At step  302 , the images closest to end systole, i.e. maximum contraction, and end diastole, i.e. maximum volume of the LV, may be identified. This can be done by a user viewing all of the images on the display  112  and selecting one of them as the closest to end systole and one of them as the closest to end diastole using the user input device  114 . This selection may be made by the user on the basis of an assessment and comparison of the volume of the LV in each of the images as judged by eye, or by noting the points of opening and closing of the mitral valve, or using the QRS complex on an ECG plot, or by any combination of these. This is reasonably easy for a practiced clinician to do. Alternatively the processor  108  may be arranged to use image processing techniques to identify, and measure the volume of, the LV in each of the images, compare the volumes of the LV in the different images, and identify the image with the smallest LV volume as the end systole image and the image with the largest LV volume as the end diastole image. In either case, once the end systole and end diastole images have been identified, they may be identified in the memory  110 , for example being marked with an appropriate flag, so that they can be selected and viewed by a user. 
     Referring to  FIG. 4 , once the end systole and end diastole images have been identified, corresponding points  401  on the wall of the LV at end systole  400   a  and at end diastole  400   b  may be identified at step  304 . A Cartesian coordinate system may also be defined, for example having a vertical axis (referred to as the y axis herein) through the apex  402  of the LV and extending along its longitudinal axis, and a horizontal axis (referred to as the x axis herein) through the mid-point of the LV half way between its apex  402  and its base  404 . The apex  402  and the base  404  may be identified by the user via the user input, or by image processing. The coordinate of each of the points  400   a ,  400   b  on the coordinate system may then be determined and recorded. Since the scale of the image is known from the echocardiography system, the coordinates of each of the points define the position of the point in the plane of the image, and therefore the distance between the two points in each pair indicates the distance moved by the relevant part of the heart between end systole and end diastole. Again, the identification of the points may be done manually by a user selecting each of the points on each of the images using the user input  114 , or it may be done by image processing software running on the system  100  and arranged to analyse the shapes of the LV in each of the end systole and end diastole images and identify specific points. These may include for each of the two images, for example, a point at the apex  402   a ,  402   b  of the LV at both end systole and end diastole, a point  404   a ,  406   a , at one side of the base of the LV, and a point at the other side of the base of the LV, two points at the midpoint of the LV, two points at the start of the apex, and various intermediate points spaced between. Some of these points are described in more detail below with reference to  FIGS. 5 a    and  5   b.    
     Referring to  FIG. 5 a   , which shows an echo image acquired with a contrast agent, in each of the images of the LV, the apex  602  of the LV can be located as the extreme end of the LV, and the base of the LV on each side  604 ,  605  can be located from the shape of the side walls. The y axis can then be defined as the line passing through the apex  602  and the midpoint between the two sides of the base  604 ,  605 . The x axis can then be defined as the line perpendicular to the y axis half way between the apex and the midpoint between the two sides of the base. The mid-point on each side  606 ,  607  can be identified as the point where the x axis intersects the side wall on that side. The lower end of the apex on each side  608 ,  609  can also be identified where the sidewalls start to taper towards the apex  602 . As mentioned above, each of these points may be identified by a user. Alternatively image processing may be used to identify them. If image processing is used, the outline of the LV is first identified as the boundary between the lighter area within the LV and the darker area of the myocardium forming the walls around it (or vice versa for images acquired without use of a contrast agent). This boundary is not sharp, but algorithms for identifying such boundaries are well known. Once the boundary has been identified, the algorithm may then be arranged to identify the highest point (maximum y value) of the boundary as being the apex  602 , and the points where the boundary changes direction at the lower end, for example as can be seen at the point  605  on the right hand side of the base line in  FIG. 5 a   . Again algorithms for analysing the radius and direction of curvature, and how that changes around the boundary, can be used to identify these points, and the points  608 ,  609  at the lower end of the apex. 
     Referring to  FIG. 5 b   , further points on the walls of the LV can be identified, either manually or by the processor using simple algorithms. For example these might be points on the side walls equally spaced in the y direction between the points indicated in  FIG. 5   a.    
     Referring back to  FIG. 3 , once all of these points have been identified, their x and y coordinates in the Cartesian coordinate system may be stored in the memory  110 , for example as an end systole coordinate set including the coordinates of the points on the end systole image and an end diastole coordinate set including the coordinates of the points on the end diastole image. The processor may be arranged at step  306  to calculate, from the two coordinate sets, the transformation in geometry of the LV between end systole and end diastole. For example the processor may be arranged to use the coordinate sets to calculate movement in one or more directions as will now be described in more detail. 
     Referring back to  FIG. 4 , the processor  108  is arranged to calculate, for the deformation of the shape of the LV between end systole and end diastole, values for various parameters that quantify the movement of the LV between end systole and end diastole. 
     The calculation may include working out how far each point has moved in each of the x and y directions, by working out the change in position (End diastole−End systole) along both the x axis and the y axis. This gives a set of x axis movements Δx, with one value for each corresponding pair of points, as shown in  FIG. 4  for the points  404   a ,  404   b , and a set of y axis movements Δy, again with one value for each corresponding pair of points. Each of these values may be a simple distance with no indication of direction. The mean change of all the points in both the x axis (ΔX) and y axis (ΔY) may then be calculated separately so as to provide an average Δx value or x direction movement ΔX, and an average Δy value or y direction movement ΔY for the entire ventricle. If each of the individual movement values are purely distance, without any indication of whether they are in the positive or negative x or y direction, then these averages will describe the total amount of movement, but not give an indication of the direction or of whether different parts of the LV wall are moving in the same direction or opposite directions. 
     Another parameter that maybe calculated is, for each point on the LV, i.e. each pair of points on the images, to calculate the mean of the x and y direction movements Δx and Δy, where the mean value for each point Δxy=(Δx+Δy)/2. The mean of all the values of Δxy for all points can then be calculated to a value for the entire ventricle ΔXY. This calculation is similar to the calculation of shear strain and is therefore referred to herein as the shear transformation. It will be appreciated that, for a given distance of movement, this parameter will be largest for movements at 45 degrees to both of the x and y axes, and smallest for movements along one of the axes. 
     A further parameter that can be calculated is similar to the principal transformation that can be calculated from x and y strain components, and is therefore referred to herein as the principal transformation, given by 
       principal transformation= C 1(Δ X+ΔY −√(Δ X+ΔY ){circumflex over ( )}2+ C 2Δ XY{circumflex over ( )} 2)
 
     where C1 and C2 are constants. For example C1 may be ½ and C2 may be 4. These values were used in the examples described below. 
     This transformation is closely related to the shear transformation and therefore tends to vary in a similar way to that parameter, but has a negative value indicating contraction of the heart. However, as indicated by the test results below, the principal transformation value can give a more reliable diagnosis in some cases, in particular of CAD. 
     It will be appreciated that each of these parameters relates to changes between end systole and end diastole in a single coronary cycle. However in stress echocardiography, (or corresponding tests carried out with other imaging methods) there will be one value for each parameter for the heart at rest and one value for the heart at stress. Comparing those values, for example determining the difference between them, gives further information about heart function that can be used in diagnosis. 
     Once the x and y movements, and shear and principal transformation values have been calculated, the processor is then arranged at step  308  to compare these with reference values stored in the memory  110  to make a diagnosis of one or more specific heart conditions, and to generate a diagnostic output. The output may be a simple binary output indicating a positive or negative diagnosis. The processor unit  106  may be arranged to display the output on the display  112 . Alternatively, or in addition, it may be arranged to store the output as data in association with the images on which it was based, for example by adding output data, indicative of the diagnosis, to a file in which the images are stored. 
     The reference values may for example be determined by analysis of images of hearts some of which do and some of which do not have the specific heart conditions to determine for example threshold values which are indicative of a specific condition. 
     The reference values can be determined by means of a learning algorithm which, for example, can be run on the processor unit  106 , and which uses a database of stress echo images with associated diagnoses as determined by conventional methods, which may be stored in the memory  110 . Specifically the database may include a large number of sets of images, each set comprising an end systole image and an end diastole image for both rest condition and stress condition, together with, for each set of images, an associated diagnosis, such as a positive or negative diagnosis for CAD. The learning algorithm may be arranged to analyse the images to calculate values of the various parameters described above, and then to determine the correlation between the diagnosis and the values of each of the various parameters. 
     Analysis was carried out on sample images from 70 subjects. All results generated were from an apical 4 chamber view. Firstly the values were compared for positive and negative outcomes as determined from the DSE results. Then the comparison was repeated with the DSE results corrected for confirmed false positives in the DSE results. 
     Table 1 Shows values of the principal transformation (in mm), shear transformation value (in mm), and mean ΔX (in mm) at rest and stress for DSE outcome (1=Pos, 2=Neg) in the Apical 4 Chamber view. 
                            Group Statistics                                                     Std.   Std. Error           DSE_Result   N   Mean   Deviation   Mean                                                 Stress_Prin   1.00   9   −6.8214   4.08788   1.36263           2.00   61   −8.9260   2.20018   .28170       Rest_Prin   1.00   9   −7.7332   3.86497   1.28832           2.00   61   −9.3163   2.41589   .30932       Rest_Shr   1.00   9   17.7267   9.16943   3.05648           2.00   61   21.5356   5.50610   .70498       Stress_Shr   1.00   9   17.0074   8.06969   2.68990           2.00   61   22.2608   4.56871   .58496       Rest_X   1.00   9   18.8694   11.02116   3.67372           2.00   61   21.8492   6.65078   .85155       Stress_X   1.00   9   19.9334   9.80639   3.26880           2.00   61   25.8710   7.43965   .95255                    
Table 2 Shows means of Principal transformation value (in mm), Shear transformation (in mm) and X transformation (in mm) at rest and stress for Adjusted DSE outcome (1=Pos, 2=Neg).
 
                            Group Statistics                                                     Std.   Std. Error           Adjusted_DSE   N   Mean   Deviation   Mean                                                 Stress_Prin   1.00   7   −4.4716   1.29120   .48803           2.00   63   −9.1203   2.24588   .28295       Rest_Prin   1.00   7   −5.3352   1.21275   .45838           2.00   63   −9.5325   2.44136   .30758       Rest_Shr   1.00   7   12.0645   2.74525   1.03761           2.00   63   22.0438   5.58342   .70344       Stress_Shr   1.00   7   12.2348   3.81629   1.44242           2.00   63   22.6243   4.44025   .55942       Rest_X   1.00   7   11.6937   2.73459   1.03358           2.00   63   22.5519   6.84823   .86280       Stress_X   1.00   7   14.1727   4.81157   1.81860           2.00   63   26.3226   7.29318   .91885                    
Table 3 Shows Independent samples T-Test for variables vs adjusted DSE.
 
     
       
         
           
               
            
               
                   
               
               
                 Independent Samples Test 
               
            
           
           
               
               
               
               
            
               
                   
                 Levene&#39;s Test for 
                   
                   
               
               
                   
                 Equality of Variances 
                   
                 Sig. 
               
            
           
           
               
               
               
               
               
               
            
               
                   
                 F 
                 Sig. 
                 t 
                 df 
                 (2-tailed) 
               
               
                   
                   
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Stress_Prin 
                 Equal variances 
                 1.705 
                 .196 
                 5.356 
                 68 
                 .000 
               
               
                   
                 assumed 
               
               
                   
                 Equal variances 
                   
                   
                 8.240 
                 10.596 
                 .000 
               
               
                   
                 not assumed 
               
               
                 Rest_Prin 
                 Equal variances 
                 2.355 
                 .130 
                 4.466 
                 68 
                 .000 
               
               
                   
                 assumed 
               
               
                   
                 Equal variances 
                   
                   
                 7.604 
                 12.377 
                 .000 
               
               
                   
                 not assumed 
               
               
                 Rest_8 hr 
                 Equal variances 
                 2.106 
                 .151 
                 −4.644 
                 68 
                 .000 
               
               
                   
                 assumed 
               
               
                   
                 Equal variances 
                   
                   
                 −7.961 
                 12.527 
                 .000 
               
               
                   
                 not assumed 
               
               
                 Stress_8 hr 
                 Equal variances 
                 .194 
                 .661 
                 −5.942 
                 68 
                 .000 
               
               
                   
                 assumed 
               
               
                   
                 Equal variances 
                   
                   
                 −6.715 
                 7.923 
                 .000 
               
               
                   
                 not assumed 
               
               
                 Rest_X 
                 Equal variances 
                 5.696 
                 .020 
                 −4.136 
                 68 
                 .000 
               
               
                   
                 assumed 
               
               
                   
                 Equal variances 
                   
                   
                 −8.065 
                 16.500 
                 .000 
               
               
                   
                 not assumed 
               
               
                 Stress_X 
                 Equal variances 
                 .927 
                 .339 
                 −4.290 
                 68 
                 .000 
               
               
                   
                 assumed 
               
               
                   
                 Equal variances 
                   
                   
                 −5.963 
                 9.395 
                 .000 
               
               
                   
                 not assumed 
               
               
                   
               
            
           
         
       
     
     Machine Learning Results 
     From the values of the various parameters obtained from the sample data, machine learning may be used to determine the accuracy of each parameter as an indicator of adjusted DSE outcome. Using the data above, a J48 pruned decision tree with  10  fold cross validation method was used to classify the data. The accuracy of each parameter as an indicator of diagnostic outcome is summarized in the tables below, in which the following abbreviations used are: 
     TP=true positive
 
FP=false positive
 
FN=false negative
 
TN=true negative
 
PPV=positive predictive value
 
NPV=negative predictive value
 
     
       
         
           
               
             
               
                 TABLE 4 
               
               
                   
               
               
                 Accuracy of Consultant Interpretation 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                 J48 
                 TP = 6 
                 FN = 1 
               
               
                   
                 Accuracy = 94.3% 
                 FP = 3 
                 TN = 60 
               
            
           
           
               
               
               
               
            
               
                   
                 Sensitivity = 85.7% 
                 PPV = 66.7% 
                   
               
               
                   
                 Specificity = 95% 
                 NPV = 98.4% 
               
               
                   
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 5 
               
               
                   
               
               
                 Accuracy of Stress Principal Transformation 
               
               
                 for Adjusted DSE outcome 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                 J48 Value = −5.95 
                 TP = 7 
                 FN = 0 
               
               
                   
                 Accuracy = 95.7% 
                 FP = 3 
                 TN = 60 
               
            
           
           
               
               
               
               
            
               
                   
                 Sensitivity = 100% 
                 PPV = 70% 
                   
               
               
                   
                 Specificity = 95.2% 
                 NPV = 100% 
               
               
                   
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 6 
               
               
                   
               
               
                 Accuracy of Rest Principal Transformation 
               
               
                 for Adjusted DSE outcome 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                 J48 Value = −6.92 
                 TP = 5 
                 FN = 2 
               
               
                   
                 Accuracy = 88.6% 
                 FP = 6 
                 TN = 57 
               
            
           
           
               
               
               
               
            
               
                   
                 Sensitivity = 71.4 
                 PPV = 45.5% 
                   
               
               
                   
                 Specificity = 90.5% 
                 NPV = 96.6% 
               
               
                   
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 7 
               
               
                   
               
               
                 Accuracy of Stress Shear Transformation 
               
               
                 for Adjusted DSE outcome 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                 J48 Value = 15.85 
                 TP = 6 
                 FN = 1 
               
               
                   
                 Accuracy = 95.7% 
                 FP = 2 
                 TN = 61 
               
            
           
           
               
               
               
               
            
               
                   
                 Sensitivity = 85.7% 
                 PPV = 85.7 
                   
               
               
                   
                 Specificity = 96.8% 
                 NPV = 98.4 
               
               
                   
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 8 
               
               
                   
               
               
                 Accuracy of Rest Shear Transformation 
               
               
                 for Adjusted DSE Outcome 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                 J48 Value = 15.35 
                 TP = 5 
                 FN = 2 
               
               
                   
                 Accuracy = 91.4% 
                 FP = 4 
                 TN = 59 
               
            
           
           
               
               
               
               
            
               
                   
                 Sensitivity = 71.4 
                 PPV = 55.6% 
                   
               
               
                   
                 Specificity = 93.7% 
                 NPV = 96.7% 
               
               
                   
                   
               
            
           
         
       
     
     Then from all of the variables, using machine learning, a decision tree which is shown in  FIG. 7  was derived to provide accurate diagnosis from the data. The decision tree defines a series of decision points, each of which defines a reference or threshold value of a parameter. The decision tree outlines a simple algorithm which operates as follows. Firstly the principal transformation of the LV as described above is determined for the stress condition of the heart. If the transformation is less than −5.95 mm (i.e. a negative value with magnitude greater than 5.95 mm) then the diagnosis is negative. If the value is greater than −5.95 mm then difference in principal transformation between rest and stress conditions is greater than 12.278053 mm then the diagnosis is negative, but if it is less than that distance, the diagnosis is positive. It will be appreciated that the structure of the decision tree, and the reference or threshold values at each decision point in the decision tree, will depend on the diagnosis that is to be made. 
     The decision tree was then used on the sample data to test its accuracy and the outcome is given below. 
     Machine Learning on all Variables 
       
     
       
         
           
               
             
               
                 TABLE 9 
               
               
                   
               
               
                 Accuracy of J48 decision tree for Adjusted DSE Outcome 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                 J48 Value = FIG. 1 Algorithm 
                 TP = 5 
                 FN = 2 
               
               
                   
                 Accuracy = 100% 
                 FP = 4 
                 TN = 59 
               
            
           
           
               
               
               
               
            
               
                   
                 Sensitivity = 100% 
                 PPV = 100% 
                   
               
               
                   
                 Specificity = 100% 
                 NPV = 100% 
               
               
                   
                   
               
            
           
         
       
     
     To test whether a 2 chamber view could be used instead of a 4 chamber view in a similar diagnostic system, two chamber views corresponding to each of the four chamber views in the sample data were analysed in the same way to derive the same parameters of principal transformation, shear transformation, and radial (X) and longitudinal (Y) movements. 
     
       
         
           
               
             
               
                 TABLE 10 
               
               
                   
               
               
                 Intraclass correlation coefficient of translation measurement 
               
               
                 parameters between 4 chamber and 2 chamber views. 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
            
               
                   
                 Prin transformation 
                 0.84 
               
               
                   
                 Radial displacement (ΔX) 
                 −0.23 
               
               
                   
                 Shear transformation 
                 0.36 
               
               
                   
                 Longitudinal displacement (ΔY) 
                 −0.532 
               
               
                   
                   
               
            
           
         
       
     
     A very significant result is the similarity in principal transformation values between the 4 and 2 chamber view. This implies that not only is the principal vector a sensitive parameter for detecting disease, it also implies that it gives a 3D functional assessment from a 2D view 
     
       
         
           
               
             
               
                 TABLE 11 
               
             
            
               
                   
               
               
                 Principal transformation value stats for other Disease Cohorts 
               
            
           
           
               
               
               
            
               
                   
                 Principal transformation 
                 Principal transformation 
               
               
                   
                 2ch 
                 4ch 
               
               
                   
                   
               
            
           
           
               
               
               
            
               
                 HCM 
                 −4.5 
                 −3.6 
               
               
                 Mitral Regurgitation 
                 −6.0 
                 −6.1 
               
               
                 Healthy 
                 −7.7 
                 −7.5 
               
               
                   
               
            
           
         
       
     
     Table 11 illustrates that the principal transformation is reduced in other disease cohorts (hypertrophic cardiomyopathy (HCM) and mitral regurgitation) implying it is also sensitive at detecting hypertrophy, cardiomyopathies and valve disorders. Notice that the principal vector was reduced in both the 4 chamber and the 2 chamber views indicating that it is sensitive at detecting abnormalities in the heart from just a single plane. Specifically with regard to HCM where the hypertrophy occurred only in the 4 chamber view yet the principal transformation was still significantly reduced in the 2 chamber view. 
     It will be appreciated that analysis of images in just one plane can be used to diagnose a range of diseases, and that various different parameters can be used to develop a decision tree which provides more accurate diagnosis than a single parameter.