Scienze mediche e raggi X - Synchrotron Radiation · Page 1 Medicina e raggi X l Roma, 22 April...

Medicina e raggi X l Roma, 22 April 2014 l Alberto Bravin (ESRF)

Dr. Alberto Bravin, PhD

European Synchrotron Radiation Facility Grenoble, France

[email protected]

Scienze mediche e raggi X

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


X-rays in medicine

Röntgen

Children hospital, Vienna, 1921

1895 today

Cyberknife

Spiral CT

… and therapy

1971 1896

1949

Stereotaxic radiosurgery (Leksell)

CT Hounsfield

Medical diagnostics

1898

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

For radiotherapy and radiosurgery: - Up to 106X more intense than Linacs - High resolution image guidance - Energy tunability

- Nano(Micro)metric spatial resolution - New techniques (PhC, Dual energy)

- Microbeam radiation therapy - Dose enhancement therapy

Developments in low-dose phase-contrast imaging


Low dose - high resolution 3D full breast tumor detection (by PhC imaging)


Phase contrast CT + EST Dose = 2.0 ± 0.1 mGy

Dose even lower then conventional 2D mammography (~3.5 mGy)!

25 times dose saving vs clinical breast CT at same resolution

PNAS, Zhao, Brun, Coan et al., 2012, 109 (45)

Conventional CT Dose 49 ± 1 mGy

2 cm

60 keV-Voxel: 503 µm3

PMB, Mittone, Bravin, Coan, 2014 7;59(9)

No contrast agent

High resolution tissue and vascular computed tomography


The role of cellular effects during allergic bronchoconstriction (dual energy CT)

Medicina e raggi X l Roma, 22 April 2014 l Alberto Bravin (ESRF) J Appl Physiol S.Layachi, et al., 2013 July 25

Ventilation map

Tissue density map

Allergic challenge

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)

rabbit model Xe contrast agent

High resolution brain vascularization imaging


Marmoset monkey cortical vascular network

9L rat gliosarcoma cortical vascular network

. Int. J. Devl Neuroscience, L. Risser et al (2009) 27, 185–196

“The angiogenesis (- > tumor development) in primate cerebral cortex mainly occurs at capillary level”

Tracking nano-particles clusters


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

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

Where are nanoparticles going in normal and tumoral cells?


Partition of AuNPs between daughter cells during mitosis SEM (a), nanoCT (d) and microCT (e)

Astolfo et al. Nanoscale 2013, 5 (3337)

ELETTRA Tumour tracking/Biosafety

Developments in Radiation Therapy and radiation surgery


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

15

IMRT-Radiotherapy 50 Gy at the tumor location 25 fractions @ 5/week Limited by tissue tolerance

Is there another way for increasing the dose delivered to the tumour while sparing the surrounding tissues ?

Radiotherapy is only palliative for various tumor grades and locations

Dose volume effect


1mm

140Gy

25µm

4000Gy

Zeman et al, Radiat Res 15, 496,1961

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

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

Therapeutic effect of MRT


H. Smilowitz et al. J. Neurooncology, 78: 135-143, 2006

Cortical transections to treat epilepsy: fundaments


• 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)

• Epilepsy need surgery when seizures cannot be controlled pharmacogically (~10% of epileptic patients)

~1 mm

Cortical columns

Cortical columns= basic unit of the cortex

Columns: modules that interact: • Vertically with spinal cord

• Horizontally with neighborhood modules

neuron

axons

Transection shown on the rat brain atlas


M1: eloquent motor cortex (movements): if damaged-> paresis

Seizures vs. time after MRT treatment


01234567

0 3

5.5 10 15 20 25 30 35 40 45 50 55 60 65 70

hours from kainic acid injection

seiz

ures

sca

le

100 µm-360 Gy100 µm-240 Gy600 µm-250 Gy600 µm-100 Gycontrol

Romanelli et al. PLOSOne e53549 2013

Control: average over 2 rats (48h, 74 h), all other values average of 3 rats 6: generalized seizures 0: no seizures

Scienze mediche e raggi X - Synchrotron Radiation · Page 1 Medicina e raggi X l Roma, 22 April...

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