Integration of optical imaging with a small animal irradiator.

PURPOSE The authors describe the integration of optical imaging with a targeted small animal irradiator device, focusing on design, instrumentation, 2D to 3D image registration, 2D targeting, and the accuracy of recovering and mapping the optical signal to a 3D surface generated from the cone-beam computed tomography (CBCT) imaging. The integration of optical imaging will improve targeting of the radiation treatment and offer longitudinal tracking of tumor response of small animal models treated using the system. METHODS The existing image-guided small animal irradiator consists of a variable kilovolt (peak) x-ray tube mounted opposite an aSi flat panel detector, both mounted on a c-arm gantry. The tube is used for both CBCT imaging and targeted irradiation. The optical component employs a CCD camera perpendicular to the x-ray treatment/imaging axis with a computer controlled filter for spectral decomposition. Multiple optical images can be acquired at any angle as the gantry rotates. The optical to CBCT registration, which uses a standard pinhole camera model, was modeled and tested using phantoms with markers visible in both optical and CBCT images. Optically guided 2D targeting in the anterior/posterior direction was tested on an anthropomorphic mouse phantom with embedded light sources. The accuracy of the mapping of optical signal to the CBCT surface was tested using the same mouse phantom. A surface mesh of the phantom was generated based on the CBCT image and optical intensities projected onto the surface. The measured surface intensity was compared to calculated surface for a point source at the actual source position. The point-source position was also optimized to provide the closest match between measured and calculated intensities, and the distance between the optimized and actual source positions was then calculated. This process was repeated for multiple wavelengths and sources. RESULTS The optical to CBCT registration error was 0.8 mm. Two-dimensional targeting of a light source in the mouse phantom based on optical imaging along the anterior/posterior direction was accurate to 0.55 mm. The mean square residual error in the normalized measured projected surface intensities versus the calculated normalized intensities ranged between 0.0016 and 0.006. Optimizing the position reduced this error from 0.00016 to 0.0004 with distances ranging between 0.7 and 1 mm between the actual and calculated position source positions. CONCLUSIONS The integration of optical imaging on an existing small animal irradiation platform has been accomplished. A targeting accuracy of 1 mm can be achieved in rigid, homogeneous phantoms. The combination of optical imaging with a CBCT image-guided small animal irradiator offers the potential to deliver functionally targeted dose distributions, as well as monitor spatial and temporal functional changes that occur with radiation therapy.

[1]  Lei Xing,et al.  Tomographic molecular imaging of x-ray-excitable nanoparticles. , 2010, Optics letters.

[2]  Hamid Dehghani,et al.  Quantitative surface radiance mapping using multiview images of light-emitting turbid media. , 2013, Journal of the Optical Society of America. A, Optics, image science, and vision.

[3]  K. Camphausen,et al.  Imaging biomarker dynamics in an intracranial murine glioma study of radiation and antiangiogenic therapy. , 2013, International journal of radiation oncology, biology, physics.

[4]  Hamid Dehghani,et al.  Development of a multi-view multi-spectral bioluminescence tomography small animal imaging system , 2011 .

[5]  Michael S. Patterson,et al.  Bioluminescence tomography using eigenvectors expansion and iterative solution for the optimized permissible source region , 2011, Biomedical optics express.

[6]  Yujie Lu,et al.  A compact frequency-domain photon migration system for integration into commercial hybrid small animal imaging scanners for fluorescence tomography , 2012, Physics in medicine and biology.

[7]  Shengkun Shi,et al.  A generalized hybrid algorithm for bioluminescence tomography , 2013, Biomedical optics express.

[8]  Xin Liu,et al.  A Combined Fluorescence and Microcomputed Tomography System for Small Animal Imaging , 2010, IEEE Transactions on Biomedical Engineering.

[9]  Hamid Dehghani,et al.  Development of a multi-view multi-spectral bioluminescence tomography small animal imaging system , 2011 .

[10]  A. Chatziioannou,et al.  Tomographic bioluminescence imaging by use of a combined optical-PET (OPET) system: a computer simulation feasibility study , 2005, Physics in medicine and biology.

[11]  Mark Oldham,et al.  Commissioning a small-field biological irradiator using point, 2D, and 3D dosimetry techniques. , 2011, Medical physics.

[12]  M Oldham,et al.  Investigating end-to-end accuracy of image guided radiation treatment delivery using a micro-irradiator , 2013, Physics in medicine and biology.

[13]  V. Ntziachristos,et al.  FMT-XCT: in vivo animal studies with hybrid fluorescence molecular tomography–X-ray computed tomography , 2012, Nature Methods.

[14]  Eugene Wong,et al.  Implementation and commissioning of an integrated micro-CT∕RT system with computerized independent jaw collimation. , 2013, Medical physics.

[15]  Hamid Dehghani,et al.  In vivo bioluminescence tomography with a blocking-off finite-difference SP3 method and MRI/CT coregistration. , 2009, Medical physics.

[16]  Christopher H Contag,et al.  Design and evaluation of a variable aperture collimator for conformal radiotherapy of small animals using a microCT scanner. , 2007, Medical physics.

[17]  Christopher H Contag,et al.  Guided by the light: visualizing biomolecular processes in living animals with bioluminescence. , 2010, Current opinion in chemical biology.

[18]  Sasa Mutic,et al.  Progress toward a microradiation therapy small animal conformal irradiator. , 2006, Medical physics.

[19]  Hamid Dehghani,et al.  Spectrally resolved bioluminescence tomography using the reciprocity approach. , 2008, Medical physics.

[20]  Hamid Dehghani,et al.  Bioluminescence tomography improves quantitative accuracy for pre-clinical imaging , 2013, European Conference on Biomedical Optics.

[21]  Yi-Fang Huang,et al.  Comprehensive Assessment of Host Responses to Ionizing Radiation by Nuclear Factor-κB Bioluminescence Imaging-Guided Transcriptomic Analysis , 2011, PloS one.

[22]  Zhengyu Jin,et al.  Recent advances in bioluminescence tomography: methodology and system as well as application , 2015 .

[23]  D A Jaffray,et al.  Characterization of image quality and image-guidance performance of a preclinical microirradiator. , 2011, Medical physics.

[24]  Michael S. Patterson,et al.  Reconstruction algorithm for diffuse optical tomography using x-ray CT anatomical information and application to bioluminescence tomography , 2011, BiOS.

[25]  Ronald G Blasberg,et al.  Registration of planar bioluminescence to magnetic resonance and x-ray computed tomography images as a platform for the development of bioluminescence tomography reconstruction algorithms. , 2009, Journal of biomedical optics.

[26]  Kenneth M. Tichauer,et al.  Compressive sensing based reconstruction in bioluminescence tomography improves image resolution and robustness to noise , 2012, Biomedical optics express.

[27]  Venkataramanan Krishnaswamy,et al.  Radiologic and near-infrared/optical spectroscopic imaging: where is the synergy? , 2010, AJR. American journal of roentgenology.

[28]  S Mutic,et al.  MicroRT-small animal conformal irradiator. , 2007, Medical physics.

[29]  Erik Tryggestad,et al.  Small animal radiotherapy research platforms , 2011, Physics in medicine and biology.

[30]  Liji Cao,et al.  Geometrical co-calibration of a tomographic optical system with CT for intrinsically co-registered imaging , 2010, Physics in medicine and biology.

[31]  C. Contag,et al.  It's not just about anatomy: In vivo bioluminescence imaging as an eyepiece into biology , 2002, Journal of magnetic resonance imaging : JMRI.

[32]  David A Jaffray,et al.  Two-dimensional inverse planning and delivery with a preclinical image guided microirradiator. , 2013, Medical physics.

[33]  Vasilis Ntziachristos,et al.  Looking and listening to light: the evolution of whole-body photonic imaging , 2005, Nature Biotechnology.

[34]  M. Patterson,et al.  Algorithms for bioluminescence tomography incorporating anatomical information and reconstruction of tissue optical properties , 2010, Biomedical optics express.

[35]  T D Solberg,et al.  Dosimetric characterization of an image-guided stereotactic small animal irradiator , 2011, Physics in medicine and biology.

[36]  Iulian Iordachita,et al.  Accuracy of Off-Line Bioluminescence Imaging to Localize Targets in Preclinical Radiation Research. , 2013, Radiation research.

[37]  Edoardo Charbon,et al.  3D Near-Infrared Imaging Based on a Single-Photon Avalanche Diode Array Sensor , 2011 .

[38]  T D Solberg,et al.  An x-ray image guidance system for small animal stereotactic irradiation , 2010, Physics in medicine and biology.

[39]  Jie Tian,et al.  Mapping of bioluminescent images onto CT volume surface for dual-modality BLT and CT imaging. , 2012, Journal of X-ray science and technology.

[40]  Erik Tryggestad,et al.  Development of a novel preclinical pancreatic cancer research model: bioluminescence image-guided focal irradiation and tumor monitoring of orthotopic xenografts. , 2012, Translational oncology.

[41]  Timothy D Solberg,et al.  An Orthotopic Lung Tumor Model for Image-Guided Microirradiation in Rats , 2010, Radiation research.

[42]  I Iordachita,et al.  An integrated x-ray/optical tomography system for pre-clinical radiation research , 2013, Medical Imaging.

[43]  Baogang Xu,et al.  Multimodal Fluorescence-Mediated Tomography and SPECT/CT for Small-Animal Imaging , 2013, The Journal of Nuclear Medicine.

[44]  Peter Kazanzides,et al.  Image-guided small animal radiation research platform: calibration of treatment beam alignment , 2009, Physics in medicine and biology.

[45]  Michael S. Patterson,et al.  Improved bioluminescence and fluorescence reconstruction algorithms using diffuse optical tomography, normalized data, and optimized selection of the permissible source region , 2010, Biomedical optics express.

[46]  Frank Verhaegen,et al.  Development and validation of a treatment planning system for small animal radiotherapy: SmART-Plan. , 2013, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[47]  Lei Xing,et al.  X-Ray Luminescence Computed Tomography via Selective Excitation: A Feasibility Study , 2010, IEEE Transactions on Medical Imaging.

[48]  Erik Tryggestad,et al.  The small-animal radiation research platform (SARRP): dosimetry of a focused lens system , 2007, Physics in medicine and biology.

[49]  Hanli Liu,et al.  Hierarchical clustering method to improve transrectal ultrasound-guided diffuse optical tomography for prostate cancer imaging. , 2014, Academic radiology.