Patent Publication Number: US-2017358076-A1

Title: Method and Apparatus for Analyzing Nuclear Medicine Image of Myocardia

Description:
FIELD OF THE INVENTION 
     The present application relates to a method of analyzing myocardial nuclear medicine image data and an apparatus for analyzing myocardial nuclear medicine image data. 
     DESCRIPTION OF THE RELATED ART 
     Nuclear medicine technology is used to yield various types of physiological and biochemical information about the heart in many cases. Specifically, a single-photon emission computed tomography (SPECT) examination has excellent characteristics including an easy load examination, a high examination success rate, low invasiveness, and no load on kidney functions. 
     The primary image obtained from nuclear medicine measurement is prepared by the imaging of radiation count values or tissue radioactivity concentrations. Pixels corresponding to the position at which a tracer is highly accumulated have a large pixel value and are displayed brightly. However, the radiation count value or the tissue radioactivity concentration is affected by various factors, and thus even when particular pixels have a pixel value different from those of the other positions, whether the corresponding tissue is abnormal is not necessarily evident. To address this uncertainness, attempts have been made to normalize pixel values in accordance with a certain rule so as to enable quantitative evaluation of the pixel values. As such a quantitative value, a standardized uptake value (SUV) is typically used. The SUV is determined in accordance with the following formula: 
       SUV=Tissue radioactivity concentration/{Administered radiation dose/Body mass of subject}. 
     In other words, the SUV is calculated by normalization of a tissue radioactivity concentration by the administered radiation dose per body mass. In place of a simple body mass, a lean body mass is used in some cases (Non-Patent Literature 1). 
     RELATED ART DOCUMENTS 
     Non-Patent Literature 
     
         
         [Non-Patent Literature 1] Yoshifumi Sugawara, Kenneth R. Zasadny et al., “Reevaluation of the Standardized Uptake Value for FDG: Variations with Body Weight and Methods for Correction”, November 1999 Radiology, 213, 521-525. 
       
    
     SUMMARY OF THE INVENTION 
     The existing SUV is determined on the assumption that a tracer is evenly distributed in the whole body or muscle. In the case of the nuclear medicine examination of the heart, a tracer is, however, accumulated mainly in myocardia, and thus the assumption of the existing SUV may be inappropriate. On this account, there is a demand for a novel technique for quantitatively evaluating tracer accumulation. 
     An embodiment of the invention described in the present application is intended to normalize image data obtained from myocardial nuclear medicine measurement, using a value relating to the size of the heart. 
     In a preferred embodiment, the pixel value of each pixel of the myocardial nuclear medicine image data is converted into an SUV represented by the following formula: 
       SUV=Tissue radioactivity concentration/(Administered radiation dose/Value relating to size of heart). 
     The invention uses a value relating to the size of the heart in which a tracer is accumulated, as a normalization standard to normalize myocardial nuclear medicine image data. The normalization standard thus reflects actual conditions of a cardiac function more correctly than in the related art. This improves the validity of a normalized value as compared with the related art and enables more appropriate image evaluation than ever. 
     In the invention, the “value relating to the size of the heart” may be a heart weight, for example. The heart weight may be a myocardial weight, for example. The myocardial weight may be a value obtained by multiplying a myocardial volume by a density factor, for example. 
     In the invention, the “tissue radioactivity concentration” may be a value obtained by multiplying a pixel value of the myocardial nuclear medicine image data by a becquerel calibration factor (BCF). The BCF is a factor for converting a radiation count value into a radioactivity concentration (for example, Bq/ml). The BCF can be determined by a known method. For example, a nuclear medicine image of a vial (or a syringe) containing a radiopharmaceutical agent having a known total radioactivity can be taken, and the BCF can be calculated in accordance with the following formula: 
       BCF=Decay-corrected total radioactivity(Bq)/(Total count of all slices/Collection time (seconds)). 
     To determine the BCF from the data obtained using a cylindrical phantom, the following formulas may be used: 
       Volume factor=Average count value per slice/(Volume of single pixel×Collection time (seconds))
 
       BCF=Decay-corrected total radioactivity(Bq)/(Phantom volume×Volume factor).
 
     In some embodiments, the BCF may be subjected to collection time correction. The collection time correction may be performed by multiplying {Volume of single pixel [cm 3 ]/Collection time [sec]} by BCF, for example. 
     In some myocardial nuclear medicine image data, each pixel value itself may represent a radioactivity concentration. Needless to say, no BCF is needed in such a case. 
     An embodiment of the invention includes the following method. The method is for processing myocardial nuclear medicine image data and is performed through execution of a program instruction by processing means in an apparatus. 
     The method includes operating the apparatus as first means for storing a heart parameter serving as a value relating to a size of a heart and as second means for storing an administered radiation dose. 
     This method also includes converting pixel values of at least part of pixels of the image data using the values stored in the first means and the second means into SUVs in accordance with the following formula, and storing the SUVs: 
       SUV=Tissue radioactivity concentration/(Administered radiation dose/Value based on heart parameter). 
     In some embodiments, the heart parameter is a myocardial weight, and the value based on the heart parameter is also a myocardial weight. 
     In some embodiments, the heart parameter is a myocardial volume, and the value based on the heart parameter is a myocardial weight calculated by multiplying the myocardial volume by a conversion factor. 
     An embodiment of the invention includes a computer program including a program instruction configured to cause an apparatus to perform the above-described method when the computer program is executed by processing means in the apparatus. 
     Another embodiment of the invention includes an apparatus including processing means and memory means. The memory means stores a program instruction, and the program instruction is configured to perform the above-described method when the program instruction is executed by the processing means. 
     Some embodiments of the invention of the present application thought to be preferred now are specified by the appended claims. However, the configurations specified by these claims do not necessarily completely encompass all the novel technical spirit disclosed in the description and the drawings of the present application. It should be noted that the applicant claims a right to the patent of all the novel technical spirit disclosed in the description and the drawings of the present application regardless of whether the technique is described in the present claims. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         FIG. 1  is a diagram for explaining a hardware configuration of a system capable of performing the present invention; and 
         FIG. 2  is a flowchart for explaining a preferred example of SUV conversion processing for myocardial nuclear medicine images. 
     
    
    
     DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS 
     Preferred embodiments of the technical spirit disclosed in the present application will now be described with reference to the attached drawings. 
       FIG. 1  is a diagram for explaining a hardware configuration of a system  100  capable of performing the present invention. As illustrated in  FIG. 1 , the hardware configuration of the system  100  is substantially the same as those of conventional computers, and can include a CPU  102 , a main memory unit  104 , a mass storage unit  106 , a display interface  107 , a peripheral interface  108 , and a network interface  109 , for example. Similarly to conventional computers, the main memory unit  104  may be a high-speed random access memory (RAM), and the mass storage unit  106  may be an inexpensive, large-capacity hard disk or SSD. The system  100  may be connected to a display for displaying information via the display interface  107 . The system  100  may also be connected to user interfaces, such as a keyboard, a mouse, and a touch panel, via the peripheral interface  108 . The network interface  109  can be used to connect the system to other computers and the Internet via a network. 
     The mass storage unit  106  stores an operating system (OS)  110 , an SUV conversion program  120 , an alignment program  122 , and a contour extraction/volume calculation program  124 . The most basic function of the system  100  is provided through execution of the OS  110  by the CPU  102 . The SUV conversion program  120  includes program instructions relating to the novel processing disclosed in the present application. Through execution of at least part of these instructions by the CPU  102 , the system  100  can perform the novel processing disclosed in the present application. 
     The contour extraction/volume calculation program  124  includes instructions for extracting the myocardial contour. Some algorithms and software for myocardial contour extraction are known, and such an algorithm is disclosed by the present applicant in PCT International Publication (WO2013/047496A1), for example. In addition, QGS by Cedras-Sinai Medical Center, 4D-MSPECT by the University of Michigan, and pFAST by Sapporo Medical University are also disclosed as the algorithm or software for myocardial contour extraction. The program instructions included in the contour extraction/volume calculation program  124  may be configured to extract the myocardial contour using such an algorithm or software and to calculate the volume of the extracted myocardium. An embodiment of the invention disclosed in the present application can be operated together with various myocardial contour extraction algorithms, but the algorithm described in WO2013/047496A1 is preferably used to extract the myocardial contour because the algorithm has high extraction accuracy. 
     The mass storage unit  106  can further store three-dimensional nuclear medicine image data  130 . Such nuclear medicine image data is to be analyzed or operated by the programs  120  and  124 . The mass storage unit  106  can also store a collection condition file  131  that stores various data collection conditions relating to the nuclear medicine image data. The mass storage unit  106  can further store SUV data  150  prepared by converting the nuclear medicine image data  130  by the SUV conversion program  120 . 
     The system  100  can also include typical components included in a common computer system, such as a power supply and a cooler, in addition to the units illustrated in  FIG. 1 . Known embodiments of the computer system can include various forms using various techniques such as distribution, redundancy, and virtualization of memory units, use of multiple CPUs, CPU virtualization, use of a processing-specific processor such as a DSP, and a combination of hardware for particular processing performed by a CPU. The invention disclosed in the present application can be installed on any computer system, and the type of computer system does not limit the scope of the invention. The technical spirit disclosed in the present description can be typically embodied as (1) a program including instructions configured to cause an apparatus or a system including processing means to perform various types of processing described in the present description when the program is executed by the processing means; (2) a method of operating an apparatus or a system implemented by the processing means executing the program; or (3) an apparatus or a system including the program and processing means configured to execute the program, for example. As described above, software processing may be partially made into hardware. 
     It should be noted that the data  130 ,  131 , or  150 , for example, is not stored in the mass storage unit  106  in many cases while the system  100  is being produced and sold or is being started. Such data may be transferred from an external device to the system  100  via the peripheral interface  108  or the network interface  109 , for example. In some embodiments, the data  131  and  150  may be formed through execution of the SUV conversion program  120  by the CPU  102 . Depending on an installed alignment program  122  or an installed OS  110 , at least one of the data  131  and  150  is not stored in the mass storage unit  106  but is stored only in the main memory unit  104  in some cases. It should be noted that the scope of the invention disclosed in the present application is not limited by whether the data is included. 
     Next, the three-dimensional nuclear medicine image data  130  will be described in detail. The image data is obtained by nuclear medicine measurement performed on a myocardium as the tissue to be examined. In the present example, the three-dimensional nuclear medicine image data is obtained using SPECT as a nuclear medicine measurement technique. The SPECT examination of a myocardium as the tissue to be examined includes a myocardial blood flow SPECT examination to detect ischemia, for example. Known SPECT radiopharmaceutical agents suitable for the examination are  201 TlCl (thallium chloride) injection solution, technetium ( 99m Tc) tetrofosmin injection solution, and 15-(4-iodophenyl)-3(R,S)-methylpentadecanoic acid ( 123 I) injection solution, for example. 
     In the examples specifically described below, the image data  130  is image data in which each pixel value corresponds to a radiation count value. In some embodiments, the image data  130  may be image data in which each pixel value represents a tissue radioactivity concentration. 
     Next, the flow of SUV conversion processing  300  of nuclear medicine image data disclosed in the present application will be described with reference to  FIG. 2 . The processing  300  may be performed by the system  100  in which the SUV conversion program  120  is executed by the CPU  102 . In some embodiments, midway through the processing  300 , the contour extraction/volume calculation program  124  may be called from the SUV conversion program  120  and executed by the CPU  102  to perform certain processing. 
     Step  305  indicates the start of processing. In step  310 , data to be processed by the SUV conversion program  120  is loaded. In other words, all or part of the image data  130  is read from the mass storage unit  106  and is stored in the main memory unit  104 . The image data  130  may be directly imported from an external nuclear medicine apparatus into the main memory unit  104  via the network interface  109 . 
     In step  320 , various collection conditions of the image data  130  are retrieved. The various collection conditions include the following information, for example.
         A radiation dose measured before administration of a radiopharmaceutical agent to a subject (radiation dose before administration). For example, a value obtained by measuring the radiation dose of a whole administration syringe containing a radiopharmaceutical agent to be administered   The measurement date and time of a radiation dose before administration   The date and time at the start of data collection   The data collection time   A radiation dose measured after administration of the radiopharmaceutical agent to the subject (radiation dose after administration). For example, a measurement value of the radiation dose remaining in the syringe after administration   The measurement date and time of a radiation dose after administration   The half-life of a tracer contained in the radiopharmaceutical agent   Becquerel calibration factor (BCF, a factor for converting a radiation count value into a radioactivity concentration (for example, Bq/ml))       

     In some embodiments, these collection conditions may be included in the image data  130 . In such a case, the system  100  may read the information from the data  130  and store the information in the main memory unit  104  or the mass storage unit  106 . 
     In some embodiments, the system  100  may be configured to create and display a user interface (for example, a dialog box) to which an operator inputs these collection conditions. When an operator inputs intended collection conditions, the system  100  may store these collection conditions in the main memory unit  104  or the mass storage unit  106 . 
     In some embodiments, each pixel value of the image data  130  may represent a tissue radioactivity concentration. In such a case, the BCF is not used and thus is not required to be retrieved. 
     As described above, the system  100  may be configured to store the retrieved collection condition information in the main memory unit  104  or the mass storage unit  106 . In the example, the collection condition information for the image data  130  is considered to be stored in the collection condition file  131 . 
     In step  335 , the image data  130  after alignment is subjected to myocardial contour extraction. The processing in step  335  may be performed through execution of the contour extraction/volume calculation program  124  by the CPU  102 . As described above, some algorithms and software for myocardial contour extraction are known, and such an algorithm is disclosed by the present applicant in PCT International Publication (WO2013/047496A1), for example. The program instructions included in the contour extraction/volume calculation program  124  may be configured to use the algorithm to extract the myocardial contour. 
     In some embodiments, the contour extraction/volume calculation program  124  may be configured to use the extracted contour to calculate the myocardial volume. For example, the number of pixels present between the intima and the adventitia of the extracted myocardium may be multiplied by a pixel-volume conversion factor (for example, volume per pixel) to give a myocardial volume. 
     In step  340 , the radiation dose administered to a subject is calculated. The information required for the calculation of an administered radiation dose is the following information.
         A radiation dose measured before administration of a radiopharmaceutical agent to a subject (radiation dose before administration)   The measurement date and time of a radiation dose before administration   The date and time at the start of data collection   A radiation dose measured after administration of the radiopharmaceutical agent to the subject (radiation dose after administration)   The measurement date and time of the radiation dose after administration   The half-life of a tracer contained in the radiopharmaceutical agent       

     In the present example, the information is retrieved in step  320  and is stored in the collection condition file  131 . The system  100  may thus retrieve the information from the collection condition file  131  in step  340 . 
     Subsequently, an administered radiation dose is calculated in accordance with the following formulas: 
       Decay time 1 (seconds)=|Measurement date and time of radiation dose before administration−Date and time at start of data collection|
 
       Decay time 2 (seconds)=|Measurement date and time of radiation dose after administration−Date and time at start of data collection|
 
       Decay coefficient=LN(2.0)/Half-life (seconds)(LN:natural logarithm to the base  e ) 
       Administered radiation dose={Radiation dose before administration×Exp(−Decay coefficient×Decay time 1)}−{Radiation dose after administration×Exp(−Decay coefficient×Decay time 2)}.
 
     In step  345 , the pixel value of each pixel in the image data  130  is converted into an SUV. The existing SUV conversion uses the body weight of a subject for normalization. In contrast, the SUV conversion of the present embodiment is performed in accordance with formula 1. 
       SUV=Tissue radioactivity concentration/(Administered radiation dose/Myocardial weight)  [Formula 1]
 
     Each parameter will be briefly described below. 
     Tissue radioactivity concentration: it may be a value after standardization or interpolation process, for example. Each pixel value of typical nuclear medicine image data represents either a tissue radioactivity concentration or a radiation count value. When the pixel value of each pixel in image data  130  represents a radioactivity concentration, the pixel value itself can be used as the tissue radioactivity concentration. When the pixel value of each pixel in image data  130  represents a radiation count value, the value is required to be multiplied by a becquerel calibration factor (BCF), which is a factor for converting a radiation count value into a radiodensity (for example, Bq/ml), to convert the pixel value into a radioactivity concentration. When the BCF is needed, the system may be configured to retrieve the conversion factor in step  320 , for example. 
     Administered radiation dose: the administered radiation dose determined in step  340 . 
     Myocardial weight: it is calculated on the basis of the myocardium contour data obtained in step  335 . For example, the number of pixels presents between the intima and the adventitia of the extracted myocardium may be multiplied by a pixel-volume conversion factor to give a myocardial volume, and the myocardial volume may be multiplied by a myocardial volume-myocardial weight conversion factor (density factor) to give a myocardial weight. The density factor can be known literature data and may be 1.05, for example. The myocardial weight may be calculated in step  335  or in the present step. In some embodiments, the myocardial weight calculation algorithm may be installed in the contour extraction/volume calculation program  124  or in the SUV conversion program  120 . The calculated myocardial weight may be stored in the main memory unit  102  or the mass storage unit  106 . In some embodiments, the myocardial weight may be stored in a register of the CPU  102 . 
     The BCF can be determined by a known method. For example, a nuclear medicine image of a vial (or a syringe) containing a radiopharmaceutical agent having a known total radioactivity can be taken, and the BCF can be calculated in accordance with the following formula: 
       BCF=Decay-corrected total radioactivity(Bq)/(Total count of all slices/Collection time (seconds)). 
     To determine the BCF from the data obtained using a cylindrical phantom, the following formulas can be used: 
       Volume factor=Average count value per slice/(Volume of single pixel×Collection time (seconds))
 
       BCF=Decay-corrected total radioactivity (Bq)/(Phantom volume×Volume factor).
 
     In some embodiments, the BCF may be subjected to collection time correction. The collection time correction may be performed by multiplying {Volume of single pixel [cm 3 ]/Collection time [sec]} by BCF, for example. 
     The image data after conversion of the pixel value of each pixel into an SUV may be stored as SUV image data  150  in the mass storage unit  106 , for example (see  FIG. 1 ). 
     In the present example, the weight of the myocardium in which a tracer is accumulated is used as a standard to normalize myocardial nuclear medicine image data. The normalized value thus reflects actual conditions of a cardiac function more correctly than in the related art, and myocardial blood flow conditions can be imaged more objectively. In other words, the validity and reliability are improved when pieces of data are compared between different measurement dates and times and between different subjects, for example. 
     In some embodiments, the myocardial volume may be used to perform normalization in place of the myocardial weight. Alternatively, another index relating to the heart size may be used to perform normalization. 
     In step  350 , the calculation result of the increase rate of the myocardial blood flow is displayed. The display may be made in various manners. For example, when the SUV image data  150  storing the result is three-dimensional image data in which the pixel value of each pixel is converted into an SUV, the result may be displayed as brightness or color tone corresponding to the SUV at a position of the corresponding pixel on a short axis tomogram or a three-dimensional image. 
     In some embodiments, the nuclear medicine image data to be subjected to SUV conversion may be two-dimensional array data or a two-dimensional polar map in place of the three-dimensional data. In such a case, the SUV image data  150 , which is also two-dimensional array data or a two-dimensional polar map, may be displayed. 
     The invention of the present application has been specifically described with reference to preferred examples. The description and the attached drawings are not intended to limit the scope of the invention of the present application, but are intended to satisfy the requirements of the law. Embodiments of the invention of the present application include various variations in addition to the above-exemplified embodiments. For example, various numerical values shown in the description or the drawings are illustrative values and are not intended to limit the scope of the invention. Individual features included in the various examples that have been described in the description or the drawings are not limited to usage with examples in which these features are explicitly explained to be included, but may be used in combination with other examples that have been described herein or various specific examples that have not been described. In particular, the processes presented in the flowcharts do not necessarily need to be performed in the described order. According to the preference of an executor, the processes may be performed in a changed order or in parallel, or as a plurality of blocks integrally implemented, or in a loop as appropriate. These variations are all included in the scope of the invention disclosed in the present application. The form of implementing processes does not limit the scope of the invention. The order of the description of the processes defined in the claims does not necessarily specify the mandatory order of the processes. For example, an embodiment specifying a different order of the processes and an embodiment that executes the processes in a loop are also included in the scope of the invention according to the claims. 
     For example, an embodiment of the SUV conversion program  120  can include a single program, a program group including a plurality of independent programs, and a program integrated with all or part of the contour extraction/volume calculation program  124 . A program can be installed in various manners, which are well known, and all the various manners are included in the scope of the invention disclosed in the present application. 
     The novel SUV disclosed in the present application is characterized using an index relating to the size of a myocardium for normalization, and thus the SUV of the present application can be used in all the fields in which the normalization is appropriate, such as various nuclear medicine examinations of the heart. 
     It should be noted that the applicant claims to possess the right to have a patent granted on all the embodiments not deviating from the spirit of the invention regardless of whether a patent is claimed in the current set of attached claims.