Patent Publication Number: US-9842413-B2

Title: Method and apparatus for calibration of medical image data

Description:
BACKGROUND OF THE INVENTION 
     Field of the Invention 
     The present invention is directed to a method and apparatus for calibrating image data from a given medical imaging protocol. 
     Description of the Prior Art 
     In the medical imaging field, several imaging schemes are known. For example PET (Positron Emission Tomography) is a method for imaging a subject in 3D using an injected radio-active substance which is processed in the body, typically resulting in an image indicating one or more biological functions. 
     The Standardized Uptake Value (SUV) is a widely-used measure for quantifying radiotracer (especially 18F-FDG) uptake in clinical PET scans. This value is computed from the number of counts of emission events recorded per voxel in the image reconstructed from event data captured in the PET scan. Its use is intended to provide normalization for differences in patient size and body composition, along with the dose of radiotracer injected, thereby enabling inter-study comparison, both between and within individual patients. 
     While raw scan data may be expressed in units of Bq/ml, SUV is calculated as: 
     
       
         
           
             
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     This is typically simplified by assuming that the patient has a density of 1 g/ml, in which case the SUV becomes dimensionless. 
     SUVmax is the maximum observed value of SUV within a region of interest: typically a three-dimensional volume of interest, for example a representation of a lesion. 
     While differences in body composition and injected dose represent one source of variation, differences in scanner hardware and reconstruction software represent others, and these are not addressed by the use of SUV. 
     It has been observed that a single set of raw scan data may result in differing values for SUV, and so also for SUVmax, depending on the reconstruction applied to the raw scan data. A “reconstruction”, in this context, is the treatment applied to a digital photon count to convert it into image data. Practically, it is carried out by a digital computer. For example, a low resolution reconstruction will result in significant “blurring” of the image produced, so that a small lesion may appear to have a lower SUVmax than in reality, while a larger lesion of a same SUV will appear to have a larger, and possibly correct, SUVmax. Using a higher-resolution reconstruction on the same raw data will show images with more clearly-defined edges, in turn meaning that small lesions will appear to have greater SUVmax than under the lower-resolution reconstruction. SUVmax is typically the clinically-reported result of a scan. 
     It is clearly undesirable for the results of the PET scan to vary according to the reconstruction applied. For example, it may be required to evaluate a patient&#39;s progress by comparing two PET scan results taken at different times on different scanners. Each may have a different reconstruction, for example because a newer scanner has a higher resolution capacity. However, the two results must be aligned, that is, made comparable. 
     The described variations in reported results impede the acceptance of PET as a quantitative imaging tool for lesion characterization, prognostic stratification and treatment monitoring, since differences in scanner hardware and reconstruction can significantly impact generated SUV values. As such, better standardization and improved comparability between scanners and reconstruction protocols are required. 
     Two reconstructions may be performed on each data set. Typically, this will include one high-resolution reconstruction for visualization, whereby a user may be presented with an image of high quality for visual consideration, while a second lower-quality reconstruction is also performed to provide an image of a standard reference quality to enable it to be compared to images produced by lower-resolution scanners. Effectively, higher-quality image data is blurred or downgraded to provide an image of standard resolution for quantification, allowing the results from a high-resolution scanner to be compared to results from lower-resolution scanners. The higher-quality image is preferably made available for visualization by a user. 
     U.S. Pat. No. 8,755,574 and the equivalent GB2469569 address this situation, and provide for image calibration by reference to a reference object. This may be a standard “phantom”, such as a NEMA image quality phantom, well known in the art. Imaging of such a reference object allows recovery coefficients of the imaging system to be determined as the characteristics of the phantom are known a priori. 
     U.S. Pat. No. 8,755,574 and the equivalent GB2469569 describe methods for calibrating image data from a given medical imaging protocol, in particular for aligning PET images acquired using a “preferred” reading reconstruction-protocol to a “reference” reconstruction-protocol. The procedure relies on a phantom calibration step whereby an optimal filter size, which aligns data reconstructed using the “preferred” protocol to a “reference” reconstruction protocol, is estimated. The procedure is based on minimizing the differences in activity concentration recovery coefficients (RCs) calculated from a filtered version of the phantom data reconstructed with the “preferred” protocol and a reference RC curve. The filter that best aligns the RCs can then be used to align clinical PET data acquired using the “preferred” protocol to the “reference” protocol. The “preferred” reconstruction protocol is aimed at image visualization, whereas data aligned to the “reference” reconstruction-protocol (not visible to the user) is used for quantification. 
     The known method includes: (a) obtaining reference image data from a scan of a reference object using the medical imaging protocol; comparing the obtained reference image data of the reference object to standard reference image data for the reference object, and modifying the obtained reference image data to reduce an error between the obtained reference image data and the standard reference image data; and (b) obtaining subject image data from a scan of a subject using the medical imaging protocol, modifying the subject image data based on the modified reference image data, and obtaining from the modified subject image data a value of a variable for display with unmodified subject image data. 
     It is necessary to perform at least one phantom scan per phantom model on each scanner; and once for each reconstruction. It has been found to be inconvenient to have to rely on imaging a reference article, such as a phantom. In a real-life clinical setting, a suitable phantom may not be readily available. It is not a trivial task to prepare an imaging phantom for scanning, or to perform the required reconstruction of scan data. A clinical environment may lack the materials, expertise and time to perform phantom scanning for image data calibration. 
     SUMMARY OF THE INVENTION 
     The present invention accordingly aims to provide methods and apparatus for calibration of medical image data which does not require the use of an image phantom. 
     As such, the invention is particularly applicable to the multiple reconstruction of PET scan data into one high-resolution image for viewing and a second, lower-resolution image for quantification. 
     In accordance with the invention, scan image data are reconstructed for visualization and for quantification by reconstructing scan image data using a first reconstruction protocol into a visualization image, and then applying a filter to the visualization image so as to obtain a simulated reference image for quantification. A value of a filter parameter is provided to the filter. The value of the filter parameter is obtained by providing an initial value of the filter parameter to the processor in which the scan image data are reconstructed, reconstructing the scan image data using a second reconstruction protocol so as to produce a reference image suitable for quantification; 
     Comparing image-derived properties of the reference image and the simulated reference image, adapting the value of the filter parameter according to a result of the comparison, the adaptation being implemented to reduce differences in the image-derived properties of the simulated reference image with respect to the reference image, and the adapted value of the filter parameter is electronically stored. 
     The following prior art documents discuss background technology which may assist the understanding of the present invention:
     Boellaard, R., O&#39;Doherty M. J., Weber, W. A. et al (2009) FDG PET and PET/CT: EANM procedure guidelines for tumour PET imaging: version 1.0, Eur. J. Nucl. Med. Mol. Imaging, 37: 181-200.   Lasnon, C. Desmonts, C., Quak, E. et al (2013) Harmonizing SUVs in multicentre trials when using different generation PET systems: prospective validation in non-small cell lung cancer patients, Eur. J. Nucl. Med. Mol. Imaging, 40(7), 985-996.   Joshi, A., Koeppe, R. A. and Fessler, J. A. (2009) Reducing between scanner differences in multi-center PET studies, Neurolmage, 46, 154-159.   Kelly, M. D. and Declerck, J. M. (2011) SUVref: reducing reconstruction-dependent variation in PET SUV, EJNMMI Research 1:16.   

    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         FIG. 1  schematically shows a flowchart of steps involved in a method for generating visualization and reference images from a single scan data set. 
         FIG. 2  schematically shows a flowchart of steps involved in a method according to an embodiment of the present invention. 
         FIG. 3  schematically shows a flowchart of steps involved in a method according to another embodiment of the present invention. 
         FIG. 4  shows a comparison of results achieved by a calibration method according to the present invention compared to similar results obtained from a known calibration method. 
         FIG. 5  shows a method which may be used to evaluate the results of a calibration according to the present invention. 
         FIG. 6  shows a frequency plot of changes in data values after calibration according to the present invention; after calibration according to a known alternative calibration method; and without calibration. 
         FIG. 7  shows a schematic representation of apparatus according to an aspect of the present invention. 
     
    
    
     DESCRIPTION OF THE PREFERRED EMBODIMENTS 
     According to an aspect of the present invention, calibration of patient scan image data is calibrated by reference to existing patient scan images, rather than to a reference object such as a phantom. 
     In certain embodiments of the present invention, an image-based calibration method is provided, to calculate an optimal filter size required to align scan image data reconstructed with a “preferred” protocol to a “reference” protocol by using existing clinical scan image datasets available at clinical sites, without requiring a phantom calibration step. The image-based calibration procedure is enabled by a user who specifies both the “preferred” and “reference” reconstruction parameters. Subsequently, scan image data for each new patient is reconstructed using both sets of reconstruction parameters. The filter size (e.g. Gaussian kernel size), which aligns best the patient data reconstructed with the “preferred” protocol to the corresponding “reference” data, is computed using image-derived properties such as voxel-by-voxel RMS error. In certain embodiments, such filter sizes are determined for several patients, and an optimal filter for the pair of “preferred” and “reference” reconstructions is estimated across all sets of patient data. This may be by simple averaging of all optimal filter sizes. Preferably, a workflow provided by the present invention includes a stopping criterion for the inclusion of new patients such that, once an acceptably stable optimal filter size is derived, no further filter sizes for individual patients are taken into account. The optimal filter size can then be used to align clinical scan image data reconstructed using the “preferred” protocol to the “reference” protocol. 
       FIG. 1  schematically shows a flowchart of steps involved in a method susceptible to improvement according to an embodiment of the present invention. 
     A patient  10  is scanned in a scanner  20 , for example a PET scanner. This generates a set of raw scan data  22 . The raw scan data  22  is not viewable until it has been reconstructed in a reconstruction step  24 ,  24 ′. An appropriate set of parameter settings, itself known as a “protocol”, will be applied in the respective reconstruction step. 
     In a first reconstruction step  24 , a “preferred” protocol is applied, and a visualization image  26  is produced. 
     A second reconstruction step  24 ′ is also performed on the same set of raw scan data  22 . A “reference” protocol is specified by a user in order to reconstruct a reference image  28 . 
     The appropriate protocol for use in the second reconstruction step  24 ′ is specified by a user. It can, for instance, be a reconstruction protocol previously used to reconstruct image data from an older scanner, or a protocol known to produce images that closely match a proposed standard. 
     The reference image  28  is preferably of a standard resolution, for example as discussed in U.S. Pat. No. 8,755,574 and the equivalent GB2469569, to enable comparisons between image data generated by apparatus of different resolution capabilities. 
     The reference image  28  is known to be useful for quantification, while the visualization image  26  is preferred for visual interpretation by a user. 
     It is, however, desired to avoid the need to perform two separate reconstruction steps  24 ,  24 ′ on each set of raw scan data  22 . With present technology, each reconstruction takes about two minutes per bed position. With typically about 7 bed positions per scan, the reconstruction process takes about the same time again as the actual scanning. It also requires more administration and diligence for a user to maintain pairs of completely separate reconstructions and images  26 ,  28  for each scan. 
     Accordingly, embodiments of the present invention provide the further steps  30 - 40  illustrated in  FIG. 2 . A filter  30  is applied to the image data used to generate the visualization image  26 . Filter  30  may be a Gaussian filter of size σ p . It will be unique to the individual patient  10  in question, as will be discussed in further detail below. 
     The output of filter  30  acting on visualization image  26  is a simulated reference image  32   
     The step of filtering preferably comprises convolving with an image filter variable according to a given factor. The image filter may be a Gaussian filter. The factor may be the full width at half maximum of a Gaussian filter. 
     A comparison step  34  performs a voxel-wise RMS error comparison between the reference image  28  and the simulated reference image  32 . An output  36  of this comparison step is provided to the filter  30  in a feedback loop. The size σ p  of the Gaussian filter  30  may start at zero, and is adjusted in accordance with the output  36  of the voxel-wise RMS error comparison  34 . The adjusted Gaussian filter  30  is then applied to the visualization image  26  to reduce voxel-wise RMS error between reference image  28  and simulated reference image  32 . This may be in a distinct step, or may be a real-time adjustment of parameters in the filter  30 . 
     This feedback  36  of voxel-wise RMS error to control parameters of the filter  30 , such as its size σ p , continues until the reference image  28  and the simulated reference image  32  are sufficiently similar that the measured voxel-wise RMS error indicated by output  36  is minimized. 
     Once the reference image  28  and the simulated reference image  32  are sufficiently similar, the size σ p  of the Gaussian filter  30  is stored in a record  40  unique to the particular patient  10 . 
     As illustrated in  FIG. 3 , further sets of raw scan data  22  of the patient  10  need only be reconstructed  24  once, to provide a visualization image  26 . The corresponding Gaussian filter size σ p  may be retrieved from the record  40  and the corresponding filter  30  applied to the visualization image  26  to create a simulated reference image  32  suitable for quantification. 
     When a new patient  10  is imaged, the process described is repeated afresh, to store a corresponding size σ p  of the Gaussian filter  30  in a corresponding new record  40  unique to the new patient  10 . 
     Preferably, in a set-up phase, a sample of about ten patients may be imaged, and the raw scan data  22  of each may be reconstructed twice  24 ,  24 ′ as explained with reference to  FIG. 1 . Corresponding required filter sizes σ p  for generation of an acceptable simulated reference image  32  are derived and stored in patient records  40 . An average of the filter size records  40  of those patients may be used as the size of filter  30  for application to a visualization image  26  of a new patient in a method as discussed with reference to  FIG. 3 . 
     The reconstruction protocol used to generate the first “reference” image  28  may be an existing protocol from an earlier system. 
       FIG. 4  illustrates results of a comparison exercise showing a comparison between mean filter sizes for particular raw scan data sets calculated by a conventional phantom based method such as described in U.S. Pat. No. 8,755,574 and the equivalent GB2469569, and the method of the present invention. 
     The data points indicate the corresponding Gaussian filter size in millimeters, calculated as a mean filter size across respective samples of ten repeat scans of a certain phantom or across a sample of ten patients. Line  50  shows the line of unity and line  52  shows the line of linear fit. A very close agreement is observed. 
     The present invention accordingly provides a method for generating two images from a single set of raw scan data  22 : one high-resolution image  26  best for viewing and a lower-resolution image  28  which may be preferred for quantification. Only a single reconstruction is required, however, which generates the visualization image. A filter, such as a Gaussian filter, is derived for each patient based only on patient image data and is applied to the visualization image  26  to generate a corresponding quantification image, as simulated reference image  32 . 
     The estimated filter size σ p  is different across patients due to intrinsic variability. However the optimal filter size for a given pair of “preferred”-“reference” reconstruction protocols is unique and may be computed as the mean σ p  across a number of patients. 
     The invention can be used to compare (“quantise”) image data obtained from a same scanner, or at least a same type of scanner, even if different reconstruction protocols have been used. All images can be filtered to the quality of the reference image. 
     No phantom is needed. The required filter sizes are derived from patient data. Only one reconstruction  24  is now required, plus one filtering operation, which is far less time-consuming than a second reconstruction. 
     In general terms, one embodiment of the invention provides a method of calibrating image data from a given medical imaging protocol, comprising: obtaining a visualization image by reconstruction of raw scan data  22  using a reconstruction  24  and applying a filter  30  to the visualization image, to generate a simulated reference image  32 . The parameters of the filter  30  are determined from earlier comparisons of simulated reference image  32  with reference images  28  reconstructed from the corresponding raw scan data set by a standard reference standard reference reconstruction  24 ′. 
     This allows image data from any medical imaging protocol to be easily calibrated or checked against a standard for that image data. This could be a globally or regionally agreed standard for the image data, allowing repetition of results across different medical imaging protocols, such as different scanner types, or different methods of reconstruction. 
     This invention is concerned with validating a given imaging protocol and/or reconstruction against a standard reference reconstruction, and using this information to help interpret an image from the given protocol/reconstruction. It is applicable to a variety of reconstruction protocols (e.g. for different imaging modalities, such as PET, SPECT; for different reconstruction algorithms, such as OSEM). 
     Any regions of interest drawn on the visualization image may be propagated to the simulated reference image  28  for computation of quantification required for that region. The value returned in this case is labelled as SUVref—a standardised measurement of the SUV—which can then be presented alongside the image reconstructed as per the given protocol, or overlaid on the image. 
     In an alternative embodiment of this invention, as opposed to filtering the entire image  26  in order to compute SUVref measurements, a smaller region encompassing a region of interest (ROI) can instead be filtered. In this case, the simulated reference image  32  used for quantification is of the ROI only. 
     In another embodiment, a non-Gaussian—potentially, spatially non-uniform—filter can be used. This may better reflect the effects of differences in reconstruction on measured SUV. The image can also be processed using techniques other than filtering: the key element of the processing is to combine neighbouring uptake values. For example, a basic blurring effect, incorporating uptake values from neighbouring voxels, may be used. 
     The appropriate filter size σ p  is derived for each patient  10 . An average value of filter size is derived from these individual values for respective patients. The resulting average filter size may be regarded as an optimal filter size, and may be used to derive simulated reference images  32  from visualization images  26  of further patients. Patient filter sizes may be accumulated for generating the optimal filter size until a certain number of filter sizes have been calculated, or the filter sizes reach a certain criterion of variance; or another user-defined criterion. An optimal filter size may be calculated once per reconstruction protocol; and once per scanner type/software combination. 
       FIG. 5  illustrates a cross-validation study which has been performed to evaluate the effectiveness of the present invention. From a set  60  of scan data sets  22  from ten respective scanned patients  10 , nine of the scan data sets  22  are treated according to the invention as described above to arrive at a value of optimal filter size  62 . 
     The scan data set  64  for the remaining patient is rendered according to a preferred protocol to provide a visualization image  66 . The visualization image  66  is then filtered by a filter  67  derived using an image phantom, for example calculated as described in U.S. Pat. No. 8,755,574 and the equivalent GB2469569. A first simulated reference image  68  is thereby produced. In addition, the visualization image  66  is also filtered using the optimal filter size  30  obtained according to the present invention from the remaining scan data sets  22 , as discussed above, to generate a second simulated reference image  70 . 
     The first and second simulated reference images  68 ,  70  were then respectively compared  72 ,  74  to reference image  28  generated from the same patient scan data set  64  reconstructed using the “reference” protocol  24 ′. Results of these comparisons are illustrated in  FIG. 6  as a distribution of percentage change in SUVmax values between simulated reference images  68 ,  70 , as well as visualization image  66 , and reference image  28  data reconstructed using the reference protocol  24 ′. 
     The comparisons were carried out by comparing SUVmax values in regions of interest representing a sample of two to five lesions per patient in the simulated reference images  68 ,  70  to corresponding SUVmax values of the same lesions derived from images  28  reconstructed using the “reference” protocol  24 ′. 
     The comparison method illustrated in  FIG. 5  may be repeated  76 , selecting each time a different one  64  of the scan data sets  22  to be applied to phantom-derived filter  67  and to patient-derived filter  30  obtained according to the present invention from the remaining scan data sets  22 . The results of the comparison, illustrated in  FIG. 6 , shows strong agreement between frequency of values of % change in SUVmax (x-axis) for phantom-based calibration shown in curve  82  and patient-data-based calibration according to the present invention, shown in curve  84 . Curve  86  represents frequency of values of % change in SUVmax (x-axis) values for reconstruction comparing the quantification results (SUVmax) in a lesion for two different conventional “preferred” reconstruction protocols with no calibration. 
     Referring to  FIG. 7 , the above embodiments of the invention may be conveniently realized as a computer system suitably programmed with instructions for carrying out the steps of the methods according to the invention. 
     For example, a central processing unit  4  is able to receive data representative of medical scans via a port  5  which could be a reader for portable data storage media (e.g. CD-ROM); a direct link with apparatus such as a medical scanner (not shown) or a connection to a network. 
     Software applications loaded on memory  6  are executed to process the image data in random access memory  7 . 
     The processor  4  in conjunction with the software can perform the steps such as comparing simulated reference images  32  with the corresponding reference images, in the step labelled  34  in the drawings. 
     A Man—Machine Interface  8  typically includes a keyboard/mouse/screen combination which allows user input such as initiation of applications and a screen on which the results of executing the applications are displayed. 
     Although modifications and changes may be suggested by those skilled in the art, it is the intention of the inventor to embody within the patent warranted hereon all changes and modifications as reasonably and properly come within the scope of his contribution to the art.