The Indiana University Cyclotron Facility (IUCF) is a multidisciplinary laboratory performing research and development in the areas of accelerator physics, nuclear physics, materials science, biophysics and biomedical applications. Research and educational experiences are available to high school through post-doctoral students. The facility is supported by Indiana University, state and federal grants, and user fees and contracts. The laboratory is staffed by approximately 130 highly trained scientific, technical, and administrative staff members and serves approximately 60 on-site graduate students, postdoctoral research fellows and faculty members. In addition, research activities are carried out by scientists and students from around the world through collaborations, partnerships and contractual service agreements. IUCF operates one of 5 proton therapy facilities in the US.

Advanced Electron-Photon Facility (ALPHA) laser synchrotron X-ray source will enable the structural analysis of hydrated macromolecules when construction is completed in late 2009Instrumentation Development throughout all scales from nanotechnology to green field construction is performed in collaboration with researchers from within IU, nationally and internationally Low Energy Neutron Source (LENS) university-based neutron scattering platform Small Angle Neutron Scattering (SANS) enables materials science and structural biology investigations Spin Echo Scattering Angle Measurement (SESAME) will enable structural analysis of highly-ordered biological materials upon completion of construction in February, 2009Neutron Radiation Effects Program (NREP) provides low energy neutron beam for technology, research and developmentParticle Therapy Technology Development including beam delivery and diagnostic devicesPatient Specific Device Manufacture including apertures and missing tissue compensators for proton therapy treatmentsRadiation Effects Research Program (RERP) provides proton radiation for technology, research and developmentSolar Proton Radiobiology Institute for the multidisciplinary investigation of coincident physiological effects of human extraterrestrial travel within the solar system

The Indiana University Cyclotron Facility (IUCF) operates the Proton Therapy System (PTS) and manufactures medical devices under 510K approval from the FDA. This approval is based upon the IUCF Quality System Plan (QSP) that defines the good manufacturing practices established at IUCF. The QSP is described by 16 standard operating procedures (SOP):

Management Review CommitteeTier I SSC Configuration BaselineStandard Operating Procedure RequirementsDesign ControlsDocument ControlsControl of Non-ConformitiesCorrective and Preventive ActionPurchasing ControlsInspection and Test ControlsProcess ControlsQuality Records ControlsAudit ControlsImpact Analysis BoardQSP Training StandardsFDA ReportingServicing Controls

CAPA – Corrective and Preventive ActionIRB – Impact Analysis BoardMRC – Management Review CommitteeNCR - Nonconformance ReportQSP – Quality System PlanSSC - Structures, Systems and Components

o The Midwest Proton Radiotherapy Institute (MPRI) is a free-standing proton radiation therapy clinic located at IUCF and associated with the Indiana University School of Medicine (IUSM). The clinic includes a CT suite, reception area, three exam rooms, immobilization prep room, recovery room and linac suite in addition to the three treatment rooms housing the Proton Therapy System (PTS). The PTS was designed, fabricated and installed at the Indiana University Cyclotron Facility. It is the most technologically advanced proton radiation therapy machine in the US and occupies approximately one sixth of the ground floor of IUCF.

OVERVIEW

RESOURCES

RESEARCH and Development at IUCF LIST OF SERVICES

QUALITY CONTROL AND ASSURANCES

Indiana University Cyclotron Facility

http://www.iucf.indiana.edu 2401 Milo B. Sampson Ln.Bloomington, IN 47408James A. Musser, Interim DirectorPhone: (812) 855-9365Fax: (812) 855-6645

CONTACT INFORMATION

Midwest Proton Radiotherapy Institutehttp://www.mpri.org2425 Milo B. Sampson LaneBloomington, IN 47408Phone: (812) 349-5074Fax: (812) 349-5130Email: mpri@mpri.org

Neutrons interact with organic nuclei such as C and H. A neutron radiograph discloses rubber gaskets and plastic components in a gas pump . Neutron scattering is opti-mized for biological tissues & materials.

The scanning nozzle is mounted in the IUCF PTS incorporating a 360o isocentric gantry and robotic patient positioner..

The green kicker magnet during PTS installation. This magnet enables beam gating, and beam sharing.

Schematic of the kicker magnet engineering shows how the beam path is switched from one beam line to another in 9 nsec.

ALPHA electron accelerator component of the high brilliance X-ray source. This research platform is being developed in collaboration with the CRANE Naval Service Warfare Center for multidisciplinary applications.

Indiana University Cyclotron Facility

The Proton Therapy System (PTS) consists of 7 subsystems designed, fabricated and installed at IUCF/MPRI: the beam production system, the beam handling system, the beam delivery system, the dose delivery system, the radiation safety system, the patient positioning system and the integrated treatment room control system.

o The proton radiation research and development platforms, part of the Radiation Effects Research Program (RERP), share proton beam from the PTS cyclotron. Beam is delivered to each of the three treatment rooms and the two RERP stations by a fast switching system that provides protons to each of two research stations. Available at these stations are fluxes between 102 and 1011 protons/second/cm2 and momentum selected beam energies between 205MeV and 52MeV for translational physics, engineering, and biology. The unique IUCF fast switching kicker magnet system make both beam sharing and beam gating possible at MPRI and RERP.

o The Low Energy Neutron Source (LENS) is a novel, university-based pulsed neutron source that utilizes a 13MeV linear accelerator to deliver proton beam to a beryllium target by either short or long pulses. A highly optimized liquid methane moderator produces cold and very cold neutrons for use by a suite of neutron scattering instruments and development facilities. These facilities include the Small Angle Scattering Source (SANS) and SESAME, a polarized neutron source that will enable small, complex sample biophysics. TheNeutron Radiation Effects Program (NREP) station is located just beyond the first LENS moderator. It generates a neutron spectrum with a 5MeV endpoint. Directly adjacent to the RERP data collection area and across the hall from LENS is a 990 sq ft wet lab including a ventilation-isolated tissue culture (TC) room to support materials science and biological radiation experiments.

areas upon completion of construction in 2009. X-ray and VUV sources are of great importance for probing the structure and properties of biological and condensed matter systems. ALPHA will produce X-ray brilliance a factor of 10,000 times greater than the standard X-ray rotating anode facilitating macromolecular biophysics investigations, including structural analysis of hydrated biological macromolecules.

o The Advanced Photon-Electron Facility (APLHA) will serve the global research community in a wide variety

NREP station thermal modulator within LENS.

Vic Malinovsky and Ron Danis critique the newly constructed eye treatment beam line.

Age-Related Macular Degeneration (AMD) Phase 3 Clinical TrialT Ciulla3, R Danis3, V Malinovski8, S Soni8, C Bloch7, S Klein7, NO Pugh9

Vision evaluations taken at 6 month intervals disclosed unexpected stability for the control group.

Engineering drawing of the eye treatment beam line.

Cases: 24Median OS: 1.7 yrsLocal failure 28% Complications 3

Case mix:30% Base of Skull20% Head & Neck10% Vertebral column25% Brain15% Rectal/GI

Proton Treatment Planning of Patients with Implanted Metallic HardwareA O’Ryan-Blair2,3,5, A Thornton2,3, AN Schreuder5, Wen Hsi4, M Fitzek2,3

A

B

A: Eyeplan treatment plan for AMD B: overlay of eye phantom treatment verification film.

Patients: 37Mean age: 71.2 Vision at enrollment:Dose: 16Gy 20/40 – 20/400Fractions: 2 Follow up: 24 monthsCase mix: 32% classic, 11% occult, 57% mixed.

Comparison of Commissioning Results for Passive Scattering and Scanning Proton Beam Systems at MPRI M. Wolanski2,3, C. Allgower2,3, L. Coutinho2,3, J.B. Farr6, M. Fitzek2,3, R. Jesseph2,5, A. Mascia2,5, A. Thornton2,3, V. Anferov7, D. Nichiporov7

Vertebral column proton radiation treatment plan for recurrent disease following conformal x-ray therapy.

Retreatments with Proton TherapyA Thornton2,3

Representative Spread Out Bragg Peaks (SOBP) generated by the active scanning nozzle at MPRI. Maximum energy range was 208MeV. Data were collected using the IUCF MLIC and the plan was generated by XiO for protons.

1) Purdue UniversitySchool of Health Sciences,W Lafayette, Indiana2) Midwest Proton Radiotherapy Institute, Bloomington, Indiana3) Indiana University School of Medicine, Indianapolis, Indiana4) University of Florida, Jacksonville, Florida5) ProCure Treatment Centers, Bloomington, Indiana6) West German Proton Therapy Centre, Essen, Germany7) Indiana University Cyclotron Facility, Bloomington, Indiana8) School of Optometry, Bloomington, Indiana University9) Methodist Hospital, Indianapolis, Indiana

Schematic diagram of the scanning beam nozzle shows the binary carbon plate range shifter and compact x-y magnet unique to the IUCF design.

Myocardial Revascularization Following Radiation InjuryK March3, M Miller3, S Klein7

IUCF developed fast organ-motion beam gating to support investigation of myocardial revascularization. The small animal CT image below shows the calcified scarring produced by radiation damage. Beam entered from the apex.

Measurement of intra-fractional organ motion effects on simulated lung tumors:Comparison between passively scattered proton beam and a scanning proton beam delivery systemsLi Zhao1, 2, G Sandison1, Jonathan Farr6, Robert Zamenhof 2,3, and M Fitzek 2, 3