ALBA Imaging and Biomedical Applications

1. aIB ALBA Imaging and Biomedical Applications Project presented some years ago to build a Biomedical Beamline at ALBA Silvia Gil (F. Parc Taulí, UAB) and Manel Sabés (CEB-UAB)

2. OVERVIEW OF THE PROJECT TO BUILD AND DEVELOP “AIBA”

3. aIB Science to be done Biomedical Applications The Biomedical investigations are thought to be carried only in vitro and in vivo (with small animals) in preclinical studies. 1) Research in new strategies on Radiotherapy: - Minibeam Radiation Therapy (MBRT) - Radiotherapy enhanced with Nanoparticles - Dosimetric studies - Testing new generations of detectors 2) Research in Imaging: - Programs focused on Diagnosis 3) Complementary fields: - Paleontological investigations - Cultural heritage research

4. aIB - The project involving AIBA was supported by 9 Medicine and Veterinary Hospitals from Asturias, Euskadi, Madrid, Girona, Barcelona and Grenoble. - 100 researchers, 12 research centres, industries and professional associations showed interest and gave support AIBA. - L’Agència d’avaluació de noves tecnologies from Health Department of Generalitat of Catalonia helped the promoter group to prepare the project of AIBA.

5. ALBA’s synchrotron source, the Bioregion project, and the Parc de Recerca of the UAB offer all a unique synergic environment for the implementation of the AIBA Beamline. Veterinary school - UAB CBATEG (investigation with small animals) - UAB Institut Català de Paleontologia - UAB

6. NEW RADIOTHERAPEUTIC TREATMENTS AGAINST GLIOMAS FEASIBLE AT “AIBA”

7. Gliomas (overview) • Gliomas are a type of tumor arising from the glial cells, one of the main cells of the CNS. • The incident rate of gliomas is ~ 9 cases (men) and ~ 5 (women) / 100,000 inhabitants in Spain [AECC]. • Patients with high-grade glioma do not survive for more than five years after diagnosis. • Conventional treatments remain palliative mainly due to the high morbidity of surrounding healthy tissue • SYNCHROTRON RADIATION ALLOWS TO DEPOSIT CURATIVE DOSES IN THE TUMOR, WHILE KEEPING “INTACT” THE SURROUNDING HEALTHY TISSUE. Age-standarized rate (Europe, 2008, both sexes)

8. SPATIALLY FRACTIONATED RADIATION: Dose-Volume Effect: the smaller the irradiation field, the higher the healthy tissues tolerances B A Zeman et al. Histopathologic effect of high-energy-particle microbeams on the visual cortex of the mouse brain. Radiat Res 1961; 15: 15: 496-514. Figure A: 1 mm and 140 Gy, Figure B: 25 m and 4.000 Gy.

9. SPATIALLY FRACTIONATED RADIATION: 2 ·Beams width:20 - 100 μm ·c-t-c: 200 - 400 μm i) Microbeam Radiation Therapy (MRT) 3 1 - MRT was initially developed at Brookhaven National Laboratory (BNL) at National Synchrotron Light Source in New York (United States) in early 1990s (Slatkin et al. 1992). Clinical trials are currently in preparation at the ESRF. ESRF(Grenoble) - Microbeams can only be generated by synchrotron sources, limiting thus their widespread clinical implementation. MRT requires very high dose rates to deliver the dose in a very short lapse of time in order to avoid the beam smearring from any move.

10. SPATIALLY FRACTIONATED RADIATION: 2 ·Beam width: 600 μm ·c-t-c: 1200 μm ii) Minibeam Radiation Therapy (MBRT) 3 1 To implement and develop it at AIBA • Wider beams (vs microbeams) seemed to keep the sparing healthy tissue observed with microbeams (Dilmanian et al. 2006). • Minibeams do not require so high dose rates, and this technique could be developed in a conventional clinical machine with the appropiate modifications. ESRF(Grenoble) • Beams from different incident directions, with the aim of producing a broad beam at the tumor (higher doses locally), are technically much less challenging than with thinner microbeams. • The use of lower energies with MBRT leads to investigate a possible dose-enhancement in presence of chemical compounds, such as Pt, Au, I- derivates.

11. IMAGING TECHNIQUES FEASIBLE AT “AIBA”

12. IMAGING TECHNIQUES: - Analyzer-based imaging (ABI): This technique uses an analyzer crystal before the detector to enhance the phase-shift in the sample, transforming these effects in intensity at the detector. ABI allows to reconstruct the reflecting and scattering information which is directly related to several pathologies. ABI has been successfully tested in in-vitro excised breast tissues where important improvements in detail visibility and dose reduction have been achieved. Fernández M et al 2005 Phys. Med. Biol. 50 2991-3006 Keyriläinen J et al 2005 Eur. J. Radiol. 53 226-237

13. - Analyzer-based imaging combined with SAXS and USAXS: Imaging diagnosis of melanoma: - Musculoskeletal imaging Analyzer-based imaging and phase contrast imaging provide remarkable detail of cartilages, muscles, cholagen fibers. Thus, diagnosis and outcome of injuries to joint ligaments, tendons and cartilage have tremendous impact on long-term productivity, quality of life, and health care costs in animals and humans.

14. - Imaging Applications in Palaeontology Dr Xavier Delclòs, Dr. Carmen Soriano, Sr. Jaume Ortega Sr Ricardo Pérez, and Dr. Enrique Peñalver. 1)Study of the palaeobiological content of the opaque amber: The visualization of arthropods and plants embedded in opaque amber, which are otherwise impossible to see with other techniques, thanks to the penetration of synchrotron x-rays beams into the amber. 2)Microstructural study of hymenopteran's exoskeletons

15. 3)Threedimensional study of spider webs, as well as their associated content (captures, young spiders and moults) All these mentioned Radiotherapy and Imaging techniques could be feasible to be performed at the AIBA’s facilities.

16. Annexed laboratories: Chemical laboratory Cell laboratory Animal preparation room

17. Cell laboratory(asceptic conditions) • Living cells are used in several contexts: • Implantation in animals • To study the irradiation effects, the doses tolerances... • Metal content-effect studies (micro-fluorescence analysis)

18. The laboratory might be classified as L1. But L2 is more appropriate (for handling human cancer cells). • This facility would have to account with: • Incubators to keep the cell cultures. • Basic instrumentation (laminar flow hood, microscopes, liquid nitrogen tank, centrifuges,...). • More specific instrumentation for a basic cell analysis (cell counter, flow cytometer).

19. Animal preparation room One place for final animal preparation has to be foreseen in the close vicinity of the biomedical beamline. This space should include a room for anaesthesia, small surgery (i.e. introduction of catheters...). Animal housing is not foreseen at the beamline or in its close vicinities. A collaboration with the veterinary faculty of UAB and with CBATEG (Center of Animal Biotechnology and Genetic Therapy, UAB) is foreseen for the mid- and long-term housing of animals.

20. Is AIBA necessary for the Spanish research community? • Three Spanish students were carrying out the experimental part of their doctoral thesis at ID17 five years ago. • Spanish scientists from 9 different centers are users of ID17 or ID19, both at the ESRF. • Each year, one student of the master of synchrotron chose the Biomedical Applications for his experimental work. • In 2008, 10% of communications presented in the SYRAD workshop, held at the ESRF, came from Spanish scientists.

21. Is AIBA necessary for the Spanish research community? • In Spain, there are few (if any) research centers devoted to the study of both: biomedical imaging and radiotherapy techniques. This would allow a better outcome in cancer diagnosis and treatments. There are one reason more for which both La Sociedad Española de Física Médica and La Sociedad Anatómica Española give support to the biomedical beamline: • Hospital Parc Taulí (the most relevant public center on technology transfer in Catalonia) and l’Institut Català de Nanotecnologia (ICN) are few km far from ALBA.

22. Marie Curie came to Barcelona in 1931 to open the Radiotherapy departments in the Hospitals of Sant Pau and Clínic. Now, if she was alive, she would also come to inaugurate the AIBA beamline at ALBA.

23. CEB Many thanks to... ... and to you for your attention.