Dynamic Planning In Single Needle Brachytherapy Systems

					      Resonant Spectroscopy for
   Cancer Diagnosis and Therapy


“Resonant Spectroscopy Oncology Group”
 Lifetime Probability of Developing Cancer, by Site, Men, 2000-2002*
             Site                                                   Risk
             All sites†                                               1 in 2
             Prostate                                                 1 in 6
             Lung and bronchus                                      1 in 13
             Colon and rectum                                       1 in 17
             Urinary bladder‡                                       1 in 28
             Non-Hodgkin lymphoma                                   1 in 46
             Melanoma                                               1 in 52
             Kidney                                                 1 in 64
             Leukemia                                               1 in 67
             Oral Cavity                                            1 in 73
             Stomach                                                1 in 82

* For those free of cancer at beginning of age interval. Based on cancer cases diagnosed during 2000 to 2002.

‡ Includes invasive and in situ cancer cases                                                              2
Source: DevCan: Probability of Developing or Dying of Cancer Software, Version 6.0 Statistical Research and
Applications Branch, NCI, 2005. http://srab.cancer.gov/devcan
         Lifetime Probability of Developing Cancer, by Site, Women, US, 2000-2002*

             Site                                                        Risk
             All sites†                                                 1 in 3
             Breast                                                     1 in 8
             Lung & bronchus                                          1 in 17
             Colon & rectum                                           1 in 18
             Uterine corpus                                           1 in 38
             Non-Hodgkin lymphoma                                     1 in 55
             Ovary                                                    1 in 68
             Melanoma                                                 1 in 77
             Pancreas                                                 1 in 79
             Urinary bladder‡                                         1 in 88
             Uterine cervix                                           1 in 135

* For those free of cancer at beginning of age interval. Based on cancer cases diagnosed during 2000 to 2002.

‡ Includes invasive and in situ cancer cases                                                              3
Source: DevCan: Probability of Developing or Dying of Cancer Software, Version 6.0 Statistical Research and
Applications Branch, NCI, 2005. http://srab.cancer.gov/devcan
          X-Ray Diagnostic Imaging

   Includes planar x-ray (no depth resolution), CT, PET,
    other NM imaging modalities
   Used in screening, diagnostic work-up, image-guided
    biopsy and therapeutic delivery
   X-ray and CT: broadband, 20 – 200 keV, typically 80 –
    120 keV
       Bone: photoionization; soft tissues: Compton scattering
       Relies on tissue density changes to detect soft tissue
        abnormality




                                                                  4
5
   Energy range selection: Compromise
   between Image Contrast and Patient
                     Dose (absorption)


Lower   energy: greater contrast in transmission radiograph between different
tissue compositions but needs higher exposure due to higher linear absorption
    Resonant Spectroscopic Imaging: a
           paradigm change?

   Need:
       Narrowband (tunable?) light source
       Elemental composition differential between
        malignant and normal tissues
            Or tumor-seeking nanoparticles tagged with known metals
             (nanogold…) as exogenous contrast agents
       Significant difference between resonant absorption
        peaks and background cross sections (10^4?)




                                                                       7
                   Radiation Therapy

   Mostly delivered by linear accelerators at 6 – 25 MV (broadband,
    spectral peak ~ 1/3 of max. accelerator energy)
   Sometimes delivered inside the tumor (“brachytherapy”) by
    various implantable radioisotopes, 20 – 600 keV
   Primarily Compton scattering
   Relies on geometric arrangement of multiple beams/sources to
    achieve optimized dose delivery to tumor and sparing of normal or
    critical tissue
        Expensive alternative: proton (or carbon ion) therapy, Bragg peak




                                                                             8
9
10
         150 Gy




Day 34

                  11
        Resonant Activation Therapy: a
             paradigm change?

   Possible scenarios:
       Deliver energy-optimized radiation directly to
        preferentially dose tumor tissue based on elemental
        composition differences
       Two step process: high-energy radiation is directed
        to a site doped with heavy elements (nanoparticles),
        which would be thereby pumped to undergo
        fluorescent emission




                                                               12
                    X-ray fluorescence and
                          energy dispersive x-ray   Synchrotron-based system used for
                                                                                               All 4 elements are found in elevated
Geraki 2004, City         diffraction for the            detection of x-ray fluorescence
                                                                                                      levels in tumor (less pronounced
      University,         quantification of              emitted from iron, copper, zinc
                                                                                                      for iron, copper and more for
      London              elemental                      and potassium in healthy and
                                                                                                      potassium and zinc)
                          concentrations in              cancerous breast tissues.
                          breast tissue




                                                    100 excised tissue samples measured        Shape of the scatter spectrum and
                    X-ray scatter signatures for         by energy dispersive x-ray                 relative intensity diagnostic. The
Kidane 1999, UCL          normal and neoplastic          diffraction system over the                shapes are significantly different
                          breast tissues                 momentum transfer range of                 between tissue types in the
                                                         0.70 to 3.50 nm(-1)                        range 1.0 to 1.8 nm(-1)




                                                                                               Average intensity of scattering from
                                                    Small-angle x-ray scattering patterns
                                                                                                    cancerous regions is an order of
                                                          recorded from breast tissue
                    Small-angle x-ray scattering                                                    magnitude higher than the
Fernandez 2002,                                           samples containing healthy and
                          studies of human                                                          intensity from healthy regions.
     U. Helsinki                                          cancerous regions, and
                          breast tissue samples                                                     Differences of the SAXS patterns
                                                          compared with histo-
                                                                                                    are large and distinctive enough
                                                          pathological observations
                                                                                                    to suggest diagnostic power.




                                                    Evaluated the effect of the use of
                                                          synchrotron radiation to detect      Image quality of synchrotron radiation
                    Mammography with
                                                          phase perturbation effects,               images was considerably higher,
 Arfelli 2000, U.       synchrotron radiation:
                                                          which are higher than                     and the delivered dose was fully
        Trieste         phase-detection
                                                          absorption effects for soft tissue        compatible with conventional
                        techniques
                                                          in the energy range of 15-25              techniques.
                                                          keV
                                                                                                                               13
                                                        Several images acquired in the energy range 17-36 keV using a quasi-
                        Dual-energy tissue                    monochromatic x-ray source and a scintillator-coated CCD detector.
                             cancellation in                  Images acquired at high and low energies were nonlinearly combined to
Marziani 2002, U.
                             mammography with                 generate two energy-independent basis images. Suitable linear
      Ferrara & INFN
                             quasi monochromatic              combinations of these two basis images result in the elimination of the
                             x-rays                           contrast of a given material with respect to another. This makes it possible
                                                              to selectively cancel certain details in the processed image.




                                                        The absence of Compton scatter and the photoelectric interaction within tissues
                       Generation of "soft x-rays" by
                                                              improves conspicuity of lesions by 2 – 6 times. Increased attenuation of x-
                            using the free electron
                                                              rays in malignant vs. normal tissues makes tumors more obvious. K-edge
Carroll 1991,               laser as a proposed
                                                              subtraction allows chemical analysis of tumors in vivo. Radiation dose
      Vanderbilt U.         means of diagnosing
                                                              1/10 – 1/50 that delivered by conventional technique. This allows for an
                            and treating breast
                                                              increased sensitivity and specificity and permits prediction of histology,
                            cancer
                                                              negating necessity for biopsies.




                                                                                                  The mean of linear attenuation
                                                                                                       coefficients for cancers was
                                                        X-ray linear attenuation coefficients          10.9% higher than the mean of
                                                              were measured in the energy              normal tissues. CONCLUSIONS.
                       Attenuation of
                                                              range 14.15 to 18 keV, using             Differences in the linear
                             monochromatic X-rays
   Carroll 1994                                               monoenergetic x-rays from                attenuation coefficients of
                             by normal and
                                                              beamline X-19A at the National           monochromatic x-rays between
                             abnormal breast tissues
                                                              Synchrotron Light Source at              14.15 and 18 keV do exist
                                                              Brookhaven National Laboratory           between normal and cancerous
                                                                                                       tissues, but there is some degree
                                                                                                       of overlap.



                                                                                                                                    14
                   Summary

   Conventional diagnostic and therapeutic x-ray
    sources are not energy-optimized for selective
    targeting of cancer tissue
   Preliminary investigations suggest existence of
    a diagnostic/therapeutic advantage at selected
    energies
   Resonant Spectroscopy Oncology may open up
    a new field of biomedical research



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