Abstract:
Infra-red images of tumors carry the information of normal and cancerous tissues in every pixel. We developed a Dual-Spectrum Heat Pattern Separation (DS-HPS) algorithm to quantify the energy from the area of the high temperature tissues, called q H  map, and decompose the body surface into the high and normal temperature areas based on a pair of middle-wave Infra-red images and long-wave Infra-red images. Further, with longitudinal registration, we can detect the cancerous tissues and assess the chemotherapy treatment response on a pixel by pixel basis according to the change of the q H  map derived by the DS-HPS algorithm. The preliminary result shows the area and the q H  values in the high temperature area are decreased as the patients receive more chemotherapy. These suggest the proposed algorithm could capture the incremental or decremental of the energies emitted by the cancerous tissues, which has the potentials for chemotherapy assessment and early detection.

Description:
FIELD OF THE INVENTION 
     The invention relates to a method for assessing chemotherapy treatment response and early detecting the tumors. More specifically, this invention relates to quantify the energy from high temperature tissues and decompose the body surface into the high and normal temperature area based on a pair of MIR (middle-wave Infra-red) and LIR (long-wave Infra-red) images. 
     BACKGROUND OF THE INVENTION 
     Each year, about one million women are diagnosed with breast cancers in the world, which is the second leading cause of death for women. However, it can effectively improve the survival rate of patients by treating tumors at the early stage. Therefore, it is an important issue to detect the breast cancer early for the health of women. 
     Due to the advantages of non-invasion, non-contact, passivity, non-radiation and the ability of detecting the slight variations of temperature caused by neovascularization, Infrared imaging technique has been developed and employed for assessing chemotherapy treatment response. Serving as a medical imaging modality, the Infra-red (IR) image reveals the heat distribution on the surface of the human body. Cancerous tissues tend to have a higher temperature signature than their surrounding normal tissues, and for this reason, IR image has long been studied in hope to serve as an indicator for cancerous breast tissues. Nevertheless, the usefulness of IR images in detecting breast cancers remains controversial due to the physiological and environmental influence on the skin temperature distribution, and most importantly, there are no objective methods to quantitatively analyze lesion malignancy. 
     In the prior art, some methods have been reported to detect breast cancers or to assess treatment results of breast cancer chemotherapy using the IR image. These methods can be classified into two general categories, namely cross-sectional and longitudinal approaches. The cross-sectional approaches are mainly based on the comparison between the temperature of the normal area and that of the cancerous area of the breast. Although the breast area with tumors is expected to be higher than that of the normal breast area, it does not necessarily mean that the high temperature area in IR images corresponds to the tumor region (Lawson R., “Implications of surface temperatures in the diagnosis of breast cancer,” Canadian Medical Association Journal, p. 309-310, 1956, Lawson R. N., Chughtai M. S., “Breast Cancer and Body Temperature,” Canadian Medical Association Journal, p. 68-70, 1963 and Stark A. M., Way S., “The use of thermovision in the detection of early breast cancer,” Cancer, p. 1664-1670, 1974). Therefore, it is too arbitrary to use the heat pattern acquired at a single time point as the basis to determine if there is a tumor in a breast. 
     Alternatively, the longitudinal approaches attempt to determine the malignancy of breast tissues based on the variation of heat pattern over several time points. The general idea is the heat pattern of each person remains roughly unchanged under similar physiological and environmental conditions. It has been observed that the heat patch in the IR image may shrink or even disappear in what seems like a direct correlation to the tumor blood vessels breaking down and eventually disappear as treatment progress (Zylberberg B., Salat-Baroux J., Ravina J. H., et al., “Initial chemoimmunotherapy in inflammatory carcinoma of the breast,” Cancer, p. 1537-1543, 1982). However, a longitudinal approach may have the noisy variations caused by the physiological and environmental factors at different time points. Although the influence of such environmental variables as temperature, humidity, and so on, may be minimized through deliberate control, these factors could still disturb the IR intensity fluctuation and affects the quantitative estimation of IR intensity change along the time. To quantitatively analyze this subjective visual judgment on the change of a breast tumor, each breast is divided into four parts and compared with the temperature distribution of each pair of corresponding parts (Ng E. Y. K., Fok S. C., Peh Y. C., et al., “Computerized detection of breast cancer with artificial intelligence and thermograms,” Journal of Medical Engineering &amp; Technology, p. 152-157, 2002). The potential deficiency of this approach lies in the fallacious implicit assumption that the two breasts under the normal condition have the same temperature distributions. 
     In addition, prior to the present invention, the multiple-spectrum IR information is employed in a longitudinal approach at the same time in order to detect and quantify the breast cancer information collected under minimal physiological and environmental effects. By combining different energies received in the IR images of different spectrums, this approach offers an opportunity to further reduce the influence of the physiological and environmental factors. The blind source separation algorithm using two satellite-grade infrared cameras demonstrated that it is likely to detect breast cancer based on a pair of MIR and LIR breast images (Szu H., Miao L. and Qi H., “Thermodynamic free-energy minimization for unsupervised fusion of dual-color infrared breast images,” SPIE, Florida, 2006). Since this algorithm mainly counts on the minute difference between the vectors, i.e., (MIR, LIR), of the cancerous and normal tissues, further investigation is required to attain a sufficient signal-to-noise ratio for this idea to be applied in a clinical setting. 
     According to the present invention, applicants have departed from the conventional wisdom, and had conceived and implemented a new longitudinal approach to estimate the heat pattern change on the breast skin with IR photon information from a pair of MIR and LIR cameras, rather than directly estimating the likelihood that each pixel contains cancerous tissue. The effects of chemotherapy on breast cancer are effectively traced and evaluated by using this method. The invention is briefly described as follows. 
     SUMMARY OF THE INVENTION 
     To minimize these effects of physiological and environmental factors effectively, the present invention provides a new and useful quantitative analysis method used to achieve the quantitative assessment of chemotherapy and detect the locations of tumors. 
     The quantitative analysis method of the present invention is to estimate the emitted energies of the high temperature area on the body surface from a pair of MIR and LIR cameras. A dual-spectrum heat pattern separation (DS-HPS) algorithm is developed to quantify the energy from high temperature tissues, denoted as a q H  map, and decompose the body surface into the high and normal temperature area based on a pair of MIR and LIR images. Two descriptors are computed to indicate the structural and functional change of the tissues due to chemotherapy. One is the area of the high temperature region on the body surface and the other is the energies of high temperature tissues under the high temperature region. Increasing or decreasing of these two descriptors may indicate the location of tumors and effectiveness of chemotherapy, respectively. Such an analysis method to quantify the energy map makes the invented algorithm extremely suitable for testing the human body applications including non-invasive detection of human body, assessing chemotherapy treatment response, early detection and etc. 
     In accordance with one aspect of the present invention, a quantitative analysis method is provided. The quantitative analysis method includes the following steps of: 
     (a) obtaining an energy reading vector of a corresponding point pair in an LIR image and an MIR image; 
     (b) establishing a cost function for the quantitative analysis method; 
     (c) deriving evolution equations; and 
     (d) estimating an optimal q H  map. 
     Preferably, the energy reading vector is the LIR and MIR energy emitted from an unit volume of a high and a normal temperature tissue, respectively; 
     Preferably, the q H  map is the energy distribution of the high temperature tissue. 
     Preferably, the q H  map could be used to distinguish a high temperature tissue from a normal temperature tissue. 
     The above aspects and advantages of the present invention will become more readily apparent to those ordinarily skilled in the art after reviewing the following detailed descriptions and accompanying drawings, in which: 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         FIG. 1  shows that the software framework diagram of the present invention for obtaining energies distribution maps; 
         FIG. 2  contains evolution equations for a dual-spectrum heat pattern separation (DS-HPS) algorithm in the present invention; 
         FIGS. 3(   a ) and ( b ) is a pair of original middle-wave Infra-red (MIR) and long-wave Infra-red (LIR) images of a patient taken by MIR and LIR cameras, respectively; 
         FIGS. 4(   a ) and ( b ) gives the MIR and LIR images, respectively, and  FIG. 4(   c ) demonstrates the registered MIR image; and 
         FIG. 5  shows the results of the DS-HPS algorithm of MIR and LIR images taken in a sequence of chemotherapy, wherein  FIG. 5(   a ) is the results of the proposed approach for a sequence of chemotherapy,  FIG. 5(   b ) represents the area of the high temperature region (HT-area) curve and  FIG. 5(   c ) represents the energy originated from the high temperature tissues (HT-E) curves of five selected regions of interest (ROIs). 
     
    
    
     DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT 
     The present invention will now be described more specifically with reference to the following embodiments. It is to be noted that the following descriptions of preferred embodiments of this invention are presented herein for the purposes of illustration and description only it is not intended to be exhaustive or to be limited to the precise form disclosed. 
     Please refer to  FIG. 1 , which shows a quantitative q H  map being output in order to assess the chemotherapy response and detect the cancerous tissue through the present invention. As described in  FIG. 1 , the registration method  101  was used to obtain the registered image  102  in a MIR image  1001  and a LIR image  1002 , and then DS-HPS algorithm  103  could obtain the quantitative q H  and q N  maps  104  to analyze the registered image  102 . Preferably, the MIR image  1001  and the LIR image  1002  are obtained from a pair of MIR and LIR cameras. Preferably, the DS-HPS algorithm  103  uses a Blind Source Separation (BSS) concept to estimate the energy map (q H  and q N ) of the high temperature area and the normal temperature area. As a result, the longitudinal variations of the area and the q H  values in the high temperature area and its surrounding blood vessels could be computed from the quantitative q H  map  104  to indicate the location of tumors and effectiveness of chemotherapy, since the cancerous tissues tend to have a higher temperature than the surrounding normal tissues. 
     Please refer to  FIG. 2 , which shows that the cost function and evolution equations of the DS-HPS algorithm in the present invention. The DS-HPS algorithm is formulated as a blind source separation (BSS) algorithm. Let x=(x L , x M ) be the energy reading vector of a corresponding point pair in the LIR and MIR images. Suppose M N  and M N  represents the MIR energy emitted from one unit volume of a normal and a high temperature tissue, respectively. Similarly, suppose L N  and L H  represents the LIR energy emitted from one unit volume of a normal and a high temperature tissue, respectively. Moreover, let k N  and k H  be the effective volume of the normal temperature tissue and the high temperature tissue, respectively. Note that the effective volume is not equivalent to the actual volume. The effective volume takes into account the energy attenuation during the propagation from the IR photon generation site to the breast surface. The energies detected by the LIR and MIR cameras may be approximated as a linear composition of the energies of the attenuated LIR and MIR photons originated from the high temperature and normal temperature tissues as follows: 
     
       
         
           
             
               
                 
                   
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     If we let L H =A H  cos θ, M H =A H  sin θ, L N =A N  cos φ and M N =A N  sin φ, equation (1) can be represented as: 
                     [           x   L               x   M           ]     =       [           cos   ⁢           ⁢   θ           cos   ⁢           ⁢   ϕ               sin   ⁢           ⁢   θ           sin   ⁢           ⁢   ϕ           ]     ⁡     [           q   H               q   N           ]               (   2   )               
where q H =A H k H  and q N =A N k N . q H  and q N  may be considered as the quantity approximately equivalent to the energies of the attenuated LIR and MIR photons originated from the high temperature tissue and the normal temperature tissue, respectively, and θ and φ are respectively the parameters of the high temperature and the normal temperature of the detected body region.
 
     There are 4 unknowns in equation (2) but with only 2 equations. To solve this dilemma, it is assumed that the parameter φ and q N  change slowly in the normal temperature region. Based on these two assumptions, the cost function  200  of this algorithm may be formulated as: 
                     f   =     A   +   B   +   C   +   D   +       λ   ⁡     [       q   N     -     q     N   ⁢           ⁢   0         ]       2         ⁢     
     ⁢   wherein   ⁢     
     ⁢       f   =     A   +   B   +   C   +   D   +       λ   ⁡     [       q   N     -     q     N   ⁢           ⁢   0         ]       2         ,     
     ⁢     A   =       [       X   L     -     (       cos   ⁢           ⁢     θ   ·     q   H         +     cos   ⁢           ⁢     ϕ   ·     q   N           )       ]     2       ,     
     ⁢     B   =       [       X   M     -     (       sin   ⁢           ⁢     θ   ·     q   H         +     sin   ⁢           ⁢     ϕ   ·     q   N           )       ]     2       ,     
     ⁢     C   =       α   H   2     ⁡     [         (       ∂     q   H         ∂   x       )     2     +       (       ∂     q   H         ∂   y       )     2       ]         ,     
     ⁢     D   =       α   N   2     ⁡     [         (       ∂     q   N         ∂   x       )     2     +       (       ∂     q   N         ∂   y       )     2       ]         ,             (   3   )               
C and D are the smoothness constraint, q N     0    represents the initial q N  and λ is the Lagrange multiplier.
 
     The evolution equations for q N  and q H  may be derived as follows: 
                       q   N     n   +   1       =               {       [         α   H     ⁢       q   _     H   n       +     (         X   L     ⁢   cos   ⁢           ⁢   θ     +       X   M     ⁢   sin   ⁢           ⁢   θ       )       ]     ⁢     cos   ⁡     (     θ   -   ϕ     )         }     -                 [         α   N     ⁢       q   _     N   n       +     (         X   L     ⁢   cos   ⁢           ⁢   ϕ     +       X   M     ⁢   sin   ⁢           ⁢   ϕ       )     +     λ   ⁢           ⁢     q     N   ⁢           ⁢   0           ]     ⁢     (     1   +     α   H       )                   cos   2     ⁡     (     θ   -   ϕ     )       -       (     1   +     α   H       )     ⁢     (     1   +     α   N     +   λ     )             ⁢     
     ⁢       q   H     n   +   1       =                   {         α   N     ⁢       q   _     N   n       +     (         X   L     ⁢   cos   ⁢           ⁢   ϕ     +       X   M     ⁢   sin   ⁢           ⁢   ϕ       )     +     λ   ⁢           ⁢     q     N   ⁢           ⁢   0           ]     ⁢   cos   ⁢           ⁢     (     θ   -   ϕ     )       }     -                 [         α   H     ⁢       q   _     H   n       +     (         X   L     ⁢   cos   ⁢           ⁢   θ     +       X   M     ⁢   sin   ⁢           ⁢   θ       )       ]     ⁢     (     1   +     α   N     +   λ     )                   cos   2     ⁡     (     θ   -   ϕ     )       -       (     1   +     α   H       )     ⁢     (     1   +     α   N     +   λ     )                     (   4   )               
the q H  map is thresholded in such a way that all values smaller than 0.001 are to 0. The high temperature region is then defined by the remaining nonzero pixels in the q H  map.
 
     Please refer to  FIGS. 3(   a ) and ( b ), which is a pair of original MIR and LIR images of a patient taken by MIR and LIR cameras, respectively. On the right side of each IR image there is a color reference gauge for pseudo-coloring. 
     Please refer to  FIG. 4 , in which  FIGS. 4(   a ) and ( b ) are the MIR and the LIR image, respectively, and  FIG. 4(   c ) demonstrates the registered image via a registration method. 
     Please refer to  FIG. 5 , which presents the results of the DS-HPS algorithm for 5 pairs of MIR and LIR images taken in a sequence of chemotherapy. Two dates are shown on top of each column. The date on the row “IR” is the date when IR images were taken, and “chemo” is the chemotherapy day. Columns from top to bottom represent ROIs and q H  maps respectively. If the effectiveness of the chemotherapy is assessed by observing only MIR or LIR images as shown in the ROI row of  FIG. 5(   a ), it is obviously difficult to determine the change of the lesion size and its peripheral vessels quantitatively. In addition, we cannot estimate the variation of energy emitted from the cancerous tissues. However, the q H  map in the last row of  FIG. 5(   a ) clearly shows the structural change of cancerous tissues as well as the variation of energy detected from cancerous tissues. The two descriptors, i.e., HT-area and HT-E, are plotted in  FIG. 5(   b ) and ( c ). HT-area shows a decreasing trend in the overall high temperature area, consistent with the reduced tumor size as confirmed by the MRI, Ultrasound and Mammogram. The tumor location is L11/4-12/3-1/4 (11:30 to 13:00 of the left breast, 3 to 4 cm from the nipple) and the tumor size is about 2 cm×4 cm. After chemotherapy, the tumor size becomes 0.9 cm×3 cm. Based on the HT-area result, five small ROIs are selected in each q H  map for further estimate the probability of tumor in these locations and assess the response to chemotherapy.  FIG. 5(   c ) shows the HT-E descriptor of five red areas. The HT-E curves of line  4  and line  5  show an obvious decreasing trend, consistent with the reduced tumor size as confirmed by the MRI result. It could be inferred that there might be tumors in the 4th and 5th locations of the infrared image due to energy decrease after chemotherapy. There is also a decreasing trend in HT-E curve of line  3  because the 3rd location is near the 4th location. The rising and oscillation of HT-E curves of line  1  and line  2  indicate the small probability of tumor in these locations. 
     In conclusion, the DS-HPS algorithm is proposed in the present invention for quantitative assessment of chemotherapy and early detection. The proposed DS-HPS algorithm identifies the high temperature region, as well estimates the energy of the attenuated LIR and MIR photons originated from the high temperature tissue and the normal temperature tissue, respectively. These two descriptors have been devised to quantify the change of the cancerous tissues, including the lesion size and peripheral vessel structures as well as the variation of the emitted energy. The result shows that the proposed approach has the potential for quantitative assessment of chemotherapy and indicating the locations of tumors. 
     Based on the above descriptions, it is understood that the present invention is indeed an industrially applicable, novel and obvious one with values in industrial development. While the invention has been described in terms of what are presently considered to be the most practical and preferred embodiment, it is to be understood that the invention should not be limited to the disclosed embodiment. On the contrary, it is intended to cover numerous modifications and variations included within the spirit and scope of the appended claims which are to be accorded with the broadest interpretation so as to encompass all such modifications and variations. Therefore, the above description and illustration should not be taken as limiting the scope of the present invention which is defined by the appended claims.