Multi-spectral fluorescence for in-vivo determination of proton energy and range in proton therapy

Abstract

The accuracy charged-particle beam trajectories used for radiation therapy in patients is improved by providing feedback on the beam location within a patient's body or a quality assurance phantom. Particle beams impinge on a patient or phantom in an arrangement designed to deliver radiation dose to a tumor, while avoiding as much normal tissue as can be achieved. By placing fiducial markers in the tumor or phantom that contain specific atomic constituents, a detection signal consisting of atomic fluorescence is produced by the particle beam. An algorithm can combine the detected fluorescence signal with the known location of the fiducial markers to determine the location of the particle beam in the patient or phantom.

1 . A method for improving the trajectory of charged-particle beams used in cancer therapy in a subject comprising:
 (a) placing in a subject one or more fiducial markers that produce fluorescent x-rays of one or more distinct energies when struck by a charged-particle beam;   (b) determining the locations of the one or more fiducial markers;   (c) changing as a function of time the energy of a charged-particle beam which impinges on the subject;   (d) recording as a function of time fluorescent x-ray emissions from the fiducial markers when the subject is struck by the charged-particles;   (e) applying an algorithm to the recorded information to determine the location of the particle beam in the target relative to the known locations of the fiducial markers;   (f) processing the results of the algorithm in a form suitable for display; and   (g) displaying location of the particle beam position relative to the fiducial markers.   
     
     
         2 . The method of  claim 1 , further comprising changing the trajectory of the charged-particle beam based on the measurement of particle beam induced fluorescence. 
     
     
         3 . The method of  claim 1 , wherein the one or more fiducial markers have a composition which produces a first fluorescent x-ray in the energy range from 20 keV to 150 keV. 
     
     
         4 . The method of  claim 1 , wherein the one or more fiducial markers have a composition which produces a second fluorescent x-ray in the energy range from 20 keV to 150 keV that is distinct from the first fluorescent x-ray. 
     
     
         5 . The method of  claim 4 , further comprising using the ratio of the intensity of the first fluorescent x-ray and the second fluorescent x-ray to determine the attenuation thickness of the patient that the beams have traversed. 
     
     
         6 . The method of  claim 4 , wherein the one or more fiducial markers have a substantial component of the element gold (Au). 
     
     
         7 . The method of  claim 1 , wherein the fluorescent x-ray emissions are recorded using one or more scintillation detectors. 
     
     
         8 . The method of  claim 7 , wherein the one or more scintillation detectors have collimation suitable to exclude substantial response to radiation not originating from the fiducial markers. 
     
     
         9 . A method of treating a tumor in a subject, comprising
 (a) implanting one or more fiducial markers in or near the tumor;   (b) identifying an optimize trajectory for a charged-particle beam using the method of any one of  claims 1  to  8 ; and   (c) using the optimized charged-particle beam to irradiate the cancer.   
     
     
         10 . The method of  claim 9 , wherein the tumor is a lung cancer, prostate cancer, breast cancer, skull base tumor, or uveal melanoma. 
     
     
         11 . The method of  claim 9 , wherein the one or more fiducial markers are placed at one or more of the tumor margins, at one or more locations inside the tumor, or a combination thereof. 
     
     
         12 . A system for improving the accuracy of a charged-particle beam used in cancer therapy comprising:
 (a) a source of charged-particles of suitable energy for therapeutic effect which can be varied in energy as a function of time;   (b) one or more fiducial markers that produce fluorescent x-rays of one or more distinct energies when struck by a charged-particle beam;   (c) one or more fluorescent energy detectors suitable for measuring fluorescent x-rays emitted by the fiducial markers;   (d) a recorder suitable to record the energy of the charged-particle beam and the fluorescent x-ray emissions as a function of time;   (e) a processor and memory to calculate penetration of the charged-particle beam in the target based on the recorded information; and   (f) a display by which the information on penetration is presented in suitable form.   
     
     
         13 . The system of  claim 12  wherein the fiducial markers have a composition which produces a fluorescent x-ray in the energy range from 20 keV to 150 keV. 
     
     
         14 . The system of  claim 12  wherein the fiducial markers have a composition which produces a second fluorescent x-ray in the energy range from 20 keV to 150 keV that is distinct from the first fluorescent x-ray. 
     
     
         15 . The system of  claim 14 , wherein the fiducial markers have a substantial component of the element gold (Au). 
     
     
         16 . The system of any one of  claims 12 , wherein the one or more fluorescence energy detectors are scintillation detectors. 
     
     
         17 . The method of  claim 16 , wherein the one or more fluorescence energy detectors have collimation suitable to exclude substantial response to radiation not originating from the fiducial markers.