Abstract:
Deformation maps (e.g. deformation vector fields) used for correcting image-type data used in the treatment of patients in radiotherapy may be processed to eliminate inverse inconsistency and transitivity type errors which produce different results depending on the order or path of the calculation of deformation. The correction permits registration of a treatment plan with the changing patient image and accumulation of dose to a common reference frame without transformation dependent artifacts.

Description:
CROSS REFERENCE TO RELATED APPLICATION 
     BACKGROUND OF THE INVENTION 
       [0001]    The present invention relates to radiation therapy in which radiation is applied to a tumor or the like for treatment thereof, and in particular to adaptive/dose-guided radiation therapy where the radiation is applied and monitored according to spatially defined treatment plan and refined if the specific goals of the treatment plan are not being met. 
         [0002]    Radiation therapy applies high-energy radiation to cancer cells to selectively destroy those cells, both by focusing the radiation on a tumor site and by relying on increased susceptibility of cancer cells to radiation. The latter, increased susceptibility, results from a diminished ability by cancer cells to repair sub-lethal DNA damage and a higher reproduction rate of cancer cells, which can cause them to be more frequently in phases of cell division that are most susceptible to disruption by radiation. 
         [0003]    Improved outcomes in radiation therapy may be obtained by “fractionation” in which a radiation dose is applied in “fractions” spread out over multiple treatments at different times. This fractionation allows healthy cells, which are more efficient in DNA repair, to recover and increases the chance that a given cancer cell will be in a radiation-susceptible division mode at a time of treatment. 
         [0004]    In adaptive/dose-guided radiation therapy, a spatially defined treatment plan is prepared defining a desired dose. The treatment plan is defined on an image of the patient, for example taken by CT, PET or MRI imaging or the like, and used to align and control the radiation beams with respect to the patient during each fractional treatment. During treatment, the amount of dose received by each region of tissue during each treatment fraction is monitored. This monitor dose for each treatment fraction may be combined to track the progress of the treatment in meeting the goals of the treatment plan. 
         [0005]    The registration of the treatment plan with the patient and the monitoring of radiation dose over time are complicated by changes in the patient and tumor over time, for example, caused by weight loss and tumor shrinkage. For this reason, it is known to acquire new images of the patient at the time of each treatment fraction and to adjust the radiation plan to fit the current image so that radiation is applied correctly to the tissue despite changes in location and area. This yields the measured dose fraction. It is desirable to obtain the combined delivered dose from all treatment fractions to date. Measured dose fractions may be warped to a common reference frame based on one image before being combined. Generally, the treatment plan and measured dose fractions will be termed “image-type” data, reflecting the fact that they share a common coordinate structure with image data and are normally registered with an image. 
         [0006]    Registering image-type data by warping or deforming the image-type data may be provided by comparing images taken at different times during the treatment and developing a spatial mapping of corresponding volume elements between images to provide a deformation map. The deformation map may be a deformation vector field (DVF) or a set of points from which mathematical deformations can be derived (e.g. thin plate splines) or other known techniques which describes how the tissue has deformed between images. Such deformation maps can be obtained by wide variety of techniques including for example correlating subregions of the image in a block matching process that determines vectors for the deformation of each block according to regions of highest correlation. 
         [0007]    Minor errors in measuring and calculating the deformation maps can make the results of image transformation using deformation maps highly dependent on the sequence of the warping operation. For this reason, for example, warping image A to image B and then warping image B to image A will not yield the original image A. This error is termed “inverse inconsistency error”. Further warping image A to image B to image C and then back to image A will not yield the original image A nor will warping image A to image C yield the same image as warping image A to image B and thence to image C. These errors are termed “transitivity errors”. 
         [0008]    These errors can create uncertainty and confusion in the treatment planning process. One approach to correcting this problem, described in Skrinjar, O., Bistoquet, A., and Tagare, H., Symmetric and Transitive Registration of Image Sequences, Int J Biomed Imaging, 2008, article ID 686875, enforces the use of a predetermined reference image through which all transformations must be undertaken. 
       SUMMARY OF THE INVENTION 
       [0009]    The present invention reduces inverse inconsistency and transitivity errors without requiring transformation through a particular image, and in this way provides flexible image deformation which is largely indifferent to the sequence of deforming step. These results are accomplished by ensuring that individual deformation maps are inverse consistent, for example, by use of the appropriate correlation algorithm or an averaging process that can applied to any deformation map. The invention then produces transitive deformation maps by combining individual, inverse consistent deformation maps for combinations of different deformation pathways between the same endpoint images. The resulting system allows the user to arbitrarily deform image-type data among images with an expectation of consistent result when the deformation endpoints are the same regardless of the particular deformation pathway. 
         [0010]    Specifically, the present invention, in one embodiment, provides a program for transforming image-type data, registered to a first image, to a second image using a computer to receive a set of images of a treatment region of a patient representing at least three different image times. In this method Inverse consistent deformation maps are then determined between pairs of images. Transitive deformation maps between pairs of images are then generated where a pair comprises a first and second image, and where the transitive deformation maps combines the inverse consistent deformation maps between the first and second image and the inverse consistent deformation maps between the first and second images via third images of the set other than the first and second images. The transitive deformation maps may then be applied to image-type data, registered to the first image, to register the image-type data to the second image. 
         [0011]    It is thus a feature of at least one embodiment of the invention to convert measured deformation maps to transitive deformation maps permitting flexibility in changing the registration of image-type data among different images in arbitrary sequences with reduced or no transformation artifacts. 
         [0012]    The image-type data may be a treatment plan indicating a desired dose to the region. 
         [0013]    It is thus a feature of at least one embodiment of the invention to permit a treatment plan prepared with a particular planning image to be registered with later images taken at different times in a fractionated treatment while providing consistent results regardless of the sequence of the registration to the later images. 
         [0014]    Alternatively, the image-type data may be a dose image describing a received fractionated dose and the fractionated dose registered to the first image may be added to a fractionated dose registered to the second image. 
         [0015]    It is thus a feature of at least one embodiment of the invention to permit the accumulation of dose at any of the series of images with consistent results. 
         [0016]    The third images include every image of the set of images other than the first and second images. 
         [0017]    It is thus a feature of at least one embodiment of the invention to ensure the creation of robust transitive deformation maps that may be applied to images in any order to yield consistent results. 
         [0018]    The combination of the inverse consistent deformation vectors may perform an average of the combined inverse consistent DVFs on a vector by vector basis. In one implementation this average may be according to the equation: 
         [0000]    
       
         
           
             
               
                 Δ 
                 -&gt; 
               
               ij 
               
                 T 
                  
                 
                     
                 
                  
                 3 
               
             
             = 
             
               
                 
                   1 
                   
                     N 
                     - 
                     1 
                   
                 
                  
                 
                   ( 
                   
                     
                       
                         Δ 
                         -&gt; 
                       
                       ij 
                       IC 
                     
                     + 
                     
                       
                         ∑ 
                         
                           k 
                           ∈ 
                           S 
                         
                       
                        
                       
                         
                           Δ 
                           -&gt; 
                         
                         ikj 
                         IC 
                       
                     
                   
                   ) 
                 
                  
                 
                     
                 
                  
                 where 
                  
                 
                     
                 
                  
                 S 
               
               = 
               
                 { 
                 
                   
                     s 
                      
                     
                       : 
                     
                      
                     s 
                   
                   ∈ 
                   
                     
                       
                         { 
                         
                           1 
                           , 
                           
                             … 
                              
                             
                                 
                             
                              
                             N 
                           
                         
                         } 
                       
                       ⋀ 
                       s 
                     
                     ≠ 
                     
                       i 
                       ⋀ 
                       s 
                     
                     ≠ 
                     j 
                   
                 
                 } 
               
             
           
         
       
     
         [0019]    where: 
         [0020]    {right arrow over (Δ)} ij   T3  is the transitive deformation vector field between the first and second image; 
         [0021]    and 
         [0022]    {right arrow over (Δ)} ij   IC  is the inverse consistent DVFs between the first (i) and second (j) image and 
         [0023]    {right arrow over (Δ)} ikj   IC  is the inverse consistent DVFs between the first (i) and second (j) images via a third image, k. 
         [0024]    It is thus a feature of at least one embodiment of the invention to provide a mathematically tractable method of generating transitive DVFs. 
         [0025]    The invention may form the inverse consistent DVF from a primary and secondary image of each pair by combining a deformation map mapping the primary image to register with the secondary image and a deformation map mapping the secondary image to register with the primary image. 
         [0026]    It is thus a feature of at least one embodiment of the invention to provide a method of ensuring inverse consistent deformation maps for deformation maps generated by arbitrary techniques. 
         [0027]    The combining may provide an average of the deformation maps on a vector-by-vector basis. In one embodiment the average may be to the equation: 
         [0000]    
       
         
           
             
               
                 Δ 
                 -&gt; 
               
               ij 
               IC 
             
             = 
             
               
                 1 
                 2 
               
                
               
                 ( 
                 
                   
                     
                       Δ 
                       -&gt; 
                     
                     ij 
                   
                   + 
                   
                     
                       Δ 
                       -&gt; 
                     
                     ji 
                     
                       - 
                       1 
                     
                   
                 
                 ) 
               
             
           
         
       
     
         [0028]    where: 
         [0029]    {right arrow over (Δ)} ij   IC  is the inverse consistent deformation map; 
         [0030]    {right arrow over (Δ)} ij  is the deformation vector field mapping the primary image to register with the secondary image 
         [0031]    and 
         [0032]    {right arrow over (Δ)} ji   −1  is an inverse of the deformation vector field mapping the secondary image to register with the primary image. 
         [0033]    It is thus a feature of at least one embodiment of the invention to provide a method of generating inverse consistent deformation maps without the need to modify the underlying mechanism of generating the deformation map. 
         [0034]    These particular objects and advantages may apply to only some embodiments falling within the claims and thus do not define the scope of the invention. 
     
    
     
       BRIEF DESCRIPTION OF THE FIGURES 
         [0035]      FIG. 1  is a simplified diagram of the components of an intensity modulated radiation therapy system for providing accurate control of radiation dose within a treatment zone; 
           [0036]      FIG. 2  is a diagrammatic representation of a treatment plan for use with the system of  FIG. 1  as warped by DVFs to match changing tissue shape and dimension taken from a set of images acquired at different times in the treatment; 
           [0037]      FIG. 3  is a figure similar to that of  FIG. 2  showing received dose during each of the different times as warped by DVFs to a common image for determining total dose received; 
           [0038]      FIGS. 4   a - 4   b  are figures similar to those of  FIG. 3  showing two sequences of warping received dose to a common reference frame that will typically yield different results as a result of inverse inconsistency and lack of transitivity in the DVFs; 
           [0039]      FIG. 5  shows the received DVFs for two images A and B used in producing inverse consistent DVFs for the two images; 
           [0040]      FIG. 6  is a vector diagram showing a combination of received DVFs of  FIG. 5  according to the present invention to produce an inverse consistent DVF between an image A and B; 
           [0041]      FIG. 7  is a figure similar to that of  FIG. 5  showing calculation of DVFs in multiple pathways between an image A and D for producing a transitive DVF between image A and D; and 
           [0042]      FIG. 8  is a diagram similar to that of  FIG. 6  showing combination of the DVFs of  FIG. 7  to produce a transitive DVF between images A and D. 
       
    
    
     DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT 
       [0043]    Referring now to  FIG. 1 , an example radiation therapy machine  10 , suitable for use with the present invention but not limiting the present invention, may provide a radiation source  12  positionable in an orbit  14  about a patient  16  over a range of angles φ. The radiation source  12  may provide an intensity modulated radiation beam  18  comprised, for example, of multiple beamlets  20  which may be individually controlled in intensity by a computer  19  executing a stored program  21 . 
         [0044]    During treatment of the patient  16 , the intensity of each beamlets  20  is adjusted as a function of the position so of the radiation source  12  to apply radiation dose, preferentially to a tumor region  22 . The varying intensities may be controlled according to a treatment plan, for example, held in the computer  19 , where the treatment plan may be converted to a “treatment schedule” describing a relationship between intensities of the beamlets  20  as a function of angular position of the radiation source  12  in the orbit  14 . The treatment schedule may be a sinogram holding intensity values as a function of beamlet number and so or other representation understood in the art 
         [0045]    A portal imaging device  23  maybe positioned opposite the patient  16  with respect to a radiation source to provide information to the computer  19  for the determination of dose received by the patient  16  and/or for generating image sets for guiding treatment. Data such as received dose, treatment plan information, and/or images may be output on a display terminal  25  or the like as will be described below. 
         [0046]    Referring now to  FIG. 2 , the treatment plan  24  may be prepared with respect to an initial planning image  26   a  of the patient showing the tumor region  22  and surrounding tissue of the patient  16  and assigning dose limits or ranges to one or more regions related to the tumor region  22  and other regions of the patient  16 , for example those having high radiation sensitivity. The treatment plan  24  comprises image-type data registered to the planning image  26   a  and having generally the same dimensions as the planning image  26   a  with elements defining dose that map to corresponding pixels in the planning image  26   a  that map to brightness. 
         [0047]    The treatment plan  24  may be used to generate a treatment schedule  27  defining the intensity of each beamlets  20  as a function of the angle φ as described above. 
         [0048]    During a fractionated treatment, additional patient images  26   b  and  26   c  may be obtained providing depictions of tumor regions  22  and patient  16  as both change over time, for example, with weight loss or gain by the patient  16  and/or shrinkage of the tumor region  22 . As the patient  16  changes, the treatment plan  24  will need to be modified so as to conform to the regions of the treatment plan  24  to the changed dimensions of the tissue of the patient  16 , for example, from image  26   a  to image  26   b.    
         [0049]    Whether modification of the treatment plan  24  is necessary may be assessed by comparing images  26   a  and  26   b  to determine how these images  26  have been changed, for example, by correlating small areas of the images with respect to each other in a block matching process to produce a deformation map  28  such as a vector field (DVF)  28   a.  The DVF  28   a  may then be applied to the image-type data of the treatment plan  24  to produce a treatment plan  24 ′ registered with the image  26   b  (and shown superimposed on the image  26   b ). The actual dose deposited in image  26   b  may then be compared to the treatment plan  24 ′ to assess whether treatment modification is required. If so, a new treatment plan may be produced using image  26   b  and a new treatment schedule  27  (not shown) computed for treatment of the patient at the time of image  26   b.  Similarly a DVF  28   b  may be computed, for example, between images  26   a  and  26   c  and used to map the treatment plan  24  to image  26   c  as treatment plan  24 ″ for comparison of the cumulative dose to the patient at the time of image  26   c  (as always be described below). 
         [0050]    Each DVF  28  (and generally any deformation map  28 ) will have dimensions corresponding to the dimensions of the images  26  and may include set of elements  30  (for example, associated with each pixel of the images  26 ) defining a displacement of the tissue of the corresponding pixel of a source image (e.g. image  26   a ) when matched to tissue of a target image (e.g. image  26   b ). In a DVF  28  the elements will be vector  32 . As will be understood in the art, each vector  32  has a magnitude (length) and direction (angle) the latter being generally in three dimensions with only two depicted in the figures for clarity. Often the deformation map  28  is not commutative, meaning that a different deformation map  28  is produced when image  26   a  is the source image and image  26   c  is the target image as opposed to when image  26   a  is the target image and image  26   c  is the source image. When the source and target images are switched, the deformation maps will theoretically be related by one being the inverse of the other, that is, the direction of the vectors  32  being reversed, however in practice measurement and calculation errors prevent this from being the case. 
         [0051]    Referring now to  FIG. 3 , during the radiation treatment, dose images  34  may be collected indicating dose  36  actually received by the patient  16  in tissue corresponding to pixels of the images  26 . For example, multiple dose images  34   b - 34   d  may be collected at times corresponding to the acquisition of different images  26   b - 26   d.  These dose images  34  will also be termed “image-type” data because they have dimensions corresponding to the dimensions of the images  26  and are registered to a particular image  26 . In order to combine these dose images  34  together to obtain a value of the total dose received by the patient  16 , DVFs  28   c  (derived with image  26   c  as a source image and image  26   d  as a target image) and DVF  28   d  (derived with image  26   b  as a source image and image  26   d  as a target image) may be used to convert dose image  34   b  (associated with image  26   b ) and dose image  34   c  (associated with image  26   c ) to a common spatial framework consistent (registered) with image  26   d  so that they may be summed on a pixel by pixel basis as indicated by process block  38  with the dose image  34   d  to produce a composite dose image  40 . 
         [0052]    Referring now to  FIGS. 4   a  and  4   b,  as noted, the determination of DVFs  28  from actual images  26  can lead to imperfections that produce confusing anomalies in transformation of image-type data. For example, if four image-type data sets  60  labeled letter A-D, (and representing treatment plans  24  or dose images  34 ) are combined using DVF  28  such that image-type data A, B, and C are mapped to register with image-type data D and then summed, as shown in  FIG. 4   a,  to produce combined image  62 , that combined image  62  will be visibly and quantitatively different from a combined image  62 ′ produced by a mapping of image-type data A, B, and D to register with image-type data C and summed with image-type data C, and the sum then mapped using a DVF  28  to the reference frame of image D. 
         [0053]    This difference between these combined images  62  and  62 ′, resulting from different pathways of the deformation process, is caused by a lack of inverse consistency and transitivity of the DVFs  28 . The difference between these combined images  62  and  62 ′ as noted can be confusing to practitioners and could lead to treatment errors. 
         [0054]    Referring now to  FIG. 5 , the present invention solves this problem by first correcting for inverse consistency errors. Per the invention, a first DVF  28  may be computed using image  26   a  as a source image and  26   b  as a target image and an inverse DVF  28 ′ may be computed using the image  26   b  as a source image and  26   a  as a target image. Referring also to  FIG. 6 , a given vector  32  associated with corresponding data elements  30  and  30 ′ in DVF  28  will have a different length and angle than a vector  32 ′ for the same data elements  30  and  30 ′ associated with DVF  28 ′ as a result of inverse consistency errors. As a first step, the present invention provides an inverse consistent DVF by averaging the vectors  32  and  32 ′ for each data element  30  of DVF  28  and  28 ′ producing average data vector  32 ″ whose magnitude replaces the magnitude of the vectors  32  and  32 ′ for the data elements  30  in the DVFs  28  and  28 ′ and whose angle (or its inverse) provide the angle of the vectors  32  and  32 ′ in the DVFs  28  and  28 ′. This may be expressed with mathematical precision as a follows: 
         [0000]    
       
         
           
             
               
                 Δ 
                 -&gt; 
               
               ij 
               IC 
             
             = 
             
               
                 1 
                 2 
               
                
               
                 ( 
                 
                   
                     
                       Δ 
                       -&gt; 
                     
                     ij 
                   
                   + 
                   
                     
                       Δ 
                       -&gt; 
                     
                     ji 
                     
                       - 
                       1 
                     
                   
                 
                 ) 
               
             
           
         
       
     
         [0055]    where: 
         [0056]    {right arrow over (Δ)} ij   IC  is the inverse consistent DVF between a source image i and a target image j. 
         [0057]    {right arrow over (Δ)} ij  is the deformation vector field mapping the source image to register with the target image; 
         [0058]    and 
         [0059]    {right arrow over (Δ)} ji   −1  is an inverse of the deformation vector field mapping the source image to register with the target image. 
         [0060]    The result of this transformation is to provide for DVFs  28  that are inverse consistent regardless of how the underlying DVFs were calculated. 
         [0061]    Referring now to  FIG. 7 , a second step of the present invention modifies the inverse consistent DVFs  28  to eliminate transitivity problems. In this operation transitive DVF  28  between any two images  26  in a sequence, for example images  26   a  and  26   d  in a sequence of images  26   a - 26   d,  are generated from a composite of the inverse consistent DVFs  28  along every path between the two images  26   a  and  26   d  via one other image (e.g.  26   b  or  26   c ). Thus DVF  28  labeled AD will combine that DVF  28  with DVFs  28  between A and D via B (AB+BD) and between A and D via C (AC+CD). 
         [0062]    Referring to  FIG. 8 , this process can be illustrated by examining a vector  32  for a given element  30  of the resulting DVFs  28 . A given vector  32  of DVF  28  between images A and D will have a different length and angle than a vector  32 ′ being the sum of the DVFs  28  between images A and B and between B and D. These vectors  32  and  32 ′ will also be different in length and angle from the vector  32 ″ being the sum of the DVFs  28  between images A and C and between C and D. In this second step, the present invention provides a “transitive” DVF by averaging the vectors  32 ,  32 ′ and  32 ″ for each data element  30  of DVFs  28  producing an average data vector  32 ″″ which replaces the vector in the corresponding DVF  28  labeled AD. This process is repeated for each vector  32  of this DVF  28  to make DVF  28  transitive. This process may be then repeated for each DVF  28 . 
         [0063]    This process may be expressed with mathematical precision as follows: 
         [0000]    
       
         
           
             
               
                 Δ 
                 -&gt; 
               
               ij 
               
                 T 
                  
                 
                     
                 
                  
                 3 
               
             
             = 
             
               
                 
                   1 
                   
                     N 
                     - 
                     1 
                   
                 
                  
                 
                   ( 
                   
                     
                       
                         Δ 
                         -&gt; 
                       
                       ij 
                       IC 
                     
                     + 
                     
                       
                         ∑ 
                         
                           k 
                           ∈ 
                           S 
                         
                       
                        
                       
                         
                           Δ 
                           -&gt; 
                         
                         ikj 
                         IC 
                       
                     
                   
                   ) 
                 
                  
                 
                     
                 
                  
                 where 
                  
                 
                     
                 
                  
                 S 
               
               = 
               
                 { 
                 
                   
                     s 
                      
                     
                       : 
                     
                      
                     s 
                   
                   ∈ 
                   
                     
                       
                         { 
                         
                           1 
                           , 
                           
                             … 
                              
                             
                                 
                             
                              
                             N 
                           
                         
                         } 
                       
                       ⋀ 
                       s 
                     
                     ≠ 
                     
                       i 
                       ⋀ 
                       s 
                     
                     ≠ 
                     j 
                   
                 
                 } 
               
             
           
         
       
     
         [0064]    where: 
         [0065]    {right arrow over (Δ)} ij   T3  is the transitive DVFs between the first and second image; 
         [0066]    And 
         [0067]    {right arrow over (Δ)} ij   IC  is the inverse consistent DVFs between the first (i) and second (j) image 
         [0068]    and 
         [0069]    {right arrow over (Δ)} ikj   IC  is the inverse consistent DVFs between the first (i) and second (j) images via a third image, k. 
         [0070]    Once these transformations are complete, the DVFs  28  as corrected for inverse consistency and transitivity may be used in the applications described with respect to  FIGS. 2 and 3  without the introduction of inconsistencies caused by a change in ordering or sequencing of the transformation steps. 
         [0071]    It will be appreciated that the present invention is not limited to external beam radiotherapy but may also be used in brachytherapy or other radiation therapy environments. 
         [0072]    It will be appreciated that the steps described above may be implemented by the program  21  on the computer  19  or a separate computer system communicating with the computer  19  and acting with the computer  19  to implement a computational system. Certain terminology is used herein for purposes of reference only, and thus is not intended to be limiting. For example, terms such as “upper”, “lower”, “above”, and “below” refer to directions in the drawings to which reference is made. Terms such as “front”, “back”, “rear”, “bottom” and “side”, describe the orientation of portions of the component within a consistent but arbitrary frame of reference which is made clear by reference to the text and the associated drawings describing the component under discussion. Such terminology may include the words specifically mentioned above, derivatives thereof, and words of similar import. Similarly, the terms “first”, “second” and other such numerical terms referring to structures do not imply a sequence or order unless clearly indicated by the context. 
         [0073]    When introducing elements or features of the present disclosure and the exemplary embodiments, the articles “a”, “an”, “the” and “said” are intended to mean that there are one or more of such elements or features. The terms “comprising”, “including” and “having” are intended to be inclusive and mean that there may be additional elements or features other than those specifically noted. It is further to be understood that the method steps, processes, and operations described herein are not to be construed as necessarily requiring their performance in the particular order discussed or illustrated, unless specifically identified as an order of performance. It is also to be understood that additional or alternative steps may be employed. 
         [0074]    References to a computer or processor or its equivalent can be understood to include one or more microprocessors that can communicate in a stand-alone and/or a distributed environment(s), and can thus be configured to communicate via wired or wireless communications with other processors, where such one or more processor can be configured to operate on one or more processor-controlled devices that can be similar or different devices. Furthermore, references to memory, unless otherwise specified, can include one or more processor-readable and accessible memory elements and/or components that can be internal to the processor-controlled device, external to the processor-controlled device, and can be accessed via a wired or wireless network.