Medical Tourism - Role of Synchrotron in Biophysical Research

Transcription

1 Scienze mediche e raggi X Dr. Alberto Bravin, PhD European Synchrotron Radiation Facility Grenoble, France bravin@esrf.fr Page 1

2 Outline - The role of synchrotrons in biomedical research - Highlights of high-resolution and low-dose tissue imaging, in-vivo functional imaging - Microbeam Radiation Therapy: basics and methods - Application of MRT in neurosurgery

3 X-rays in medicine Medical diagnostics Röntgen 1898 CT Hounsfield Spiral CT today 1896 and therapy Cyberknife Children hospital, Vienna, 1921 Stereotaxic radiosurgery (Leksell)

4 The role of synchrotron facilities Fundamental research, develop techniques for clinics, prepare ground for compact sources For medical diagnostics: - up to 1000X more intense than scanners - tunable monochromatic energy - parallel beam - Nano(Micro)metric spatial resolution - New techniques (PhC, Dual energy) For radiotherapy and radiosurgery: - Up to 10 6 X more intense than Linacs - High resolution image guidance - Energy tunability - Microbeam radiation therapy - Dose enhancement therapy Page 4

5 Developments in low-dose phase-contrast imaging Page 5

6 Low dose - high resolution 3D full breast tumor detection (by PhC imaging) Dose even lower then conventional 2D mammography (~3.5 mgy)! 60 kev-voxel: 50 3 µm 3 Conventional CT Dose 49 ± 1 mgy Phase contrast CT + EST Dose = 2.0 ± 0.1 mgy No contrast agent 2 cm 25 times dose saving vs clinical breast CT at same resolution PNAS, Zhao, Brun, Coan et al., 2012, 109 (45) Page 6 PMB, Mittone, Bravin, Coan, ;59(9)

7 High resolution tissue and vascular computed tomography Page 7

8 The role of cellular effects during allergic bronchoconstriction (dual energy CT) Allergic challenge rabbit model Xe contrast agent Ventilation map Tissue density map Allergic challenge-> poor regional ventilation -> caused by bronchoconstriction of small peripheral airways. Ventilated alveolar area decreased. Inflammation is heterogeneous Impact on treatment (type and quantity of anti-inflammatory) Page 8 Medicina e raggi X l Roma, 22 J April Appl 2014 l Alberto Physiol Bravin (ESRF) S.Layachi, et al., 2013 July 25

9 High resolution brain vascularization imaging Marmoset monkey cortical vascular network 9L rat gliosarcoma cortical vascular network The angiogenesis (- > tumor development) in primate cerebral cortex mainly occurs at capillary level Page 9. Int. J. Devl Neuroscience, L. Risser et al (2009) 27,

10 Tracking nano-particles clusters Page 10

11 Gd and Au n-particles for imaging and therapy N-particles: very interesting contrast agent (longer vascular half-life than molecular contrast agents) can be monitored for a longer time. Gd chelate coated Au n-particles: sensitive to MRI and CT and adapted for therapy as dose enhancer CT with monochromatic X-rays: quantitative evaluation at spatial high resolution C. Alrich et al. J. Am. Chem. Soc. 2008, 130, 5908 Page 11

12 Theranostic use of Gd nanoparticles i.v. Injection of GBN colloid ([Gd3+] = 40 mm, V = 1.4 ml) Gd NPS are eliminated through kidneys-bladder MRI SR Alric et al. Nanoscale 2013;5(13):5930 Page 12

13 Where are nanoparticles going in normal and tumoral cells? Partition of AuNPs between daughter cells during mitosis SEM (a), nanoct (d) and microct (e) ELETTRA Tumour tracking/biosafety Page 13 Astolfo et al. Nanoscale 2013, 5 (3337)

14 Developments in Radiation Therapy and radiation surgery Page 14

15 Clinical mamagement of cerebral tumors - Epidemiology : 3000 cases/year in France - 65 % are high grade glioma: short life expectancy (2-36 mo) Cancer of the nervous system is the second most common form of cancer for children, after leukemia (ex: diffuse intrinsic pontine glioma Radiotherapy is only palliative for various tumor grades and locations IMRT-Radiotherapy 50 Gy at the tumor location 25 5/week Limited by tissue tolerance 15 Is there another way for increasing the dose delivered to the tumour while sparing the surrounding tissues?

16 Dose volume effect 1mm 25µm 140Gy 4000Gy Page 16 Zeman et al, Radiat Res 15, 496,1961

17 MRT: extremely high doses delivered in spatially fractionated microplans Tissue tolerance threshold dose for healthy tissue homogeneous irradiation The dose in the valleys that creates a dose offset in the tissues, has to stay below the tolerance threshold dose Page 17

18 Highly confined dose low damage on surrounding tissues ph2ax detection (DSB formation) Day 1 post MRT, 300 Gy peak 1 port 2 ports 4 ports Edges End of beams DNA damages are confined to the microbeam paths Only few cells exhibit ph2ax labeling between 2 microbeams High dose fall-off at the edges of the interlaced region Page 18

19 Therapeutic effect of MRT H. Smilowitz et al. J. Neurooncology, 78: , 2006 Page 19

20 Cortical transections to treat epilepsy: fundaments Epilepsy need surgery when seizures cannot be controlled pharmacogically (~10% of epileptic patients) Cortical spreading of epileptic activity relies on horizontal axons running mainly through layer V, where the majority of axons is located. Surgically cutting the horizontal axons can relieve seizures originating from regions of the cortex that cannot be surgically resected (eloquent cortex: motor cortex, language regions..) Epileptogenic foci located in non eloquent cortex are otherwise surgically resected) Page 20

21 Cortical columns neuron Cortical columns= basic unit of the cortex axons Columns: modules that interact: Vertically with spinal cord Horizontally with neighborhood modules ~1 mm

22 Transection shown on the rat brain atlas M1: eloquent motor cortex (movements): if damaged-> paresis Page 22

23 Seizures vs. time after MRT treatment seizures scale 100 µm-360 Gy 100 µm-240 Gy 600 µm-250 Gy 600 µm-100 Gy control hours from kainic acid injection Control: average over 2 rats (48h, 74 h), all other values average of 3 rats 6: generalized seizures 0: no seizures Page 23 Romanelli et al. PLOSOne e