Developing intraoperative ß- probes

Supervisors: !R. Faccini

E. Solfaroli ( IIT )Candidate:!

A. Russomando

Dottorato in Fisica XXVIII ciclo

Photo credit: F. Collamati

Who we are • C.H.I.R.ONE (5 people)

• Custom Hardware for Intraoperative Research-ONE

• Applied particle physics

• Collaboration with bio-engineers, nuclear medicine physicians, neurosurgeons

• Dip. Bioingegneria, Milan

• Istituto Neurologico Carlo Besta, Milan

• Istituto Europeo di Oncologia, Milan

• Policlinico Gemelli, Rome

• Arcispedale S.Maria Nuova, Reggio Emilia

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Cancer incidence• Cancers as a group account

for approximately 13% of all deaths each year

• Invasive cancer are the leading cause of death in the developed world

• In 2008 approximately 12.7 million cancers were diagnosed (world)

• Five-year relative cancer survival rates is ~68%

Surgery remains the primary therapeutic procedure

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5%18%

22%55%

INCURABLE

OTHERRADIO!

THERAPY

SURGERY!

Radio-Guided surgeryLonger survival is directly associated with the accuracy of tumor resection

Radio-guided surgery is a technique that enables the surgeon to perform complete tumor resections

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Longer survival is directly associated with the accuracy of tumor resection

Radio-Guided surgery

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!

• A radio-marked tracer is administered to the patient before surgery

Longer survival is directly associated with the accuracy of tumor resection

Radio-Guided surgery!

• A radio-marked tracer is administered to the patient before surgery

• The tracer is preferentially taken up by the tumor

• Each tumor requires its own tracer and implies different problematics

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Longer survival is directly associated with the accuracy of tumor resection

Radio-Guided surgery!

• A radio-marked tracer is administered to the patient before surgery

• The tracer is preferentially taken up by the tumor

• Each tumor requires its own tracer and implies different problematics

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• After bulk removal, a specific probe system detects the emission released by the remnants in real time

Particles of interest

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Photons: Escape from the patient99mTc, EƔ ~ 140 keV

photonelectronpositron

Positrons:Annichilate with electron, generate two photons18F, Emax = 635 keV

Electrons:Interact inside the bodyOur choice90Y, Emax = 2.3 MeV

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Gamma and ß+ probes

• Resolution problems

• High background from nearby healthy organs

• S/N limitation

• Voluminous probes

• Necessity of a shield or a veto

Only for selected cases (breast, melanoma ,….)

Gamma and ß+ probes

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ß+Ɣ• Resolution problems

• High background from nearby healthy organs

• S/N limitation

• Voluminous probes

• Necessity of a shield or a veto

Only for selected cases (breast, melanoma ,….)

ß- probe

• Low background

• Higher spatial resolution

• Lower dose delivered to the surgeon

• Small and handy probe

Extension of the technique (brain, abdomen, children,…)

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Clinical cases• Meningiomas are good candidates

to tests our idea

• High rate of recurrence after incomplete resection

• Available β- emitting tracer used for radio-metabolic treatment

• DOTATOC: somatostatin analogues that could be marked with 90Y

• Uptake expected 10:1

• Background is the result of uptake from the healthy tissues near the lesion

• Gliomas represent an even more challenging clinical case

• β- emitting tracer have to be developed�12

ALERT !!!!NEXT SLIDE COULD URTATE YOUR

SENSIBILITY

Dimension constraints

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meningioma

meningioma!mass

residuals

after removalbefore removal

• Targets:

• Compactness and small size (handy tool)

• Minimize the administrated dose (high sensitivity)

• Easy and fast way for data analysis (real time)

• Our first choice: p-terphenyl (doped with 0.1% diphenylbutadiene)

• Light material (ρ = 1.16 g/cm3)

• Low Z, scarce sensitivity to γ (Bremsstrahlung)

• Non-hygroscopic

• High Light Yield (~30K γ/MeV)

• Short light attenuation length λ ~ 5mm

Aromatic hydrocarbon isomer

C18H14

Development of the probe

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Properties of para-terphenyl as detector for alpha, beta and gamma radiation CHIRONE collaboration, submitted arXiv:1305.0442 [physics.ins-det]

Source

• Point source of 90Sr

• ß- decay 90Sr→90Y+e-+ve

• Half life (28y)

• 90Y

• ß- decay 90Y→90Zr+e-+ve

• Half life (64h)

• Maximum distance inside p-terphenyl

• 90Sr ~ 2 mm

• 90Y ~ 8 mm

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90Y

90SrEmax 0.6 MeV

Emax 2.3 MeV

E [MeV]

E [MeV]

P-Terphenylstopping power

Detector volume optimization

• Core: cylindrical scintillator of p-terphenyl

• ∅= 2.1mm, h=4 mm

• External PVC ring in order to manage it

• Abrasion with sandpaper (different grid)

• Valued with digital optical microscope

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7 mm !PVC2.1 mm

Height [mm] Rate [Hz]4.0 342.8 571.9 821.7 63

90Sr

Test setup

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Test setup

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Test setup

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with surfactant

without surfactant

4mm

• Holes filled with 90Y in saline solution

• Simulate the surgeon that explores the area looking for hot spots

• The prototype is able to detect all phantoms

• Probe-phantom distance 50 µm

Dose comparison:

• 20 kBq/ml ~ 0.21 GBq

• Dose used with gamma probes ~ 2.45 GBq

Laboratory test results

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Blind scan 1 sec/position

16 kBq/ml

R3 R2 R1 Calib Res OPBG

Detection time

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Y90-Activity 22 kBq/ml 15 kBq/ml 5 kBq/ml

Residual (0.10 ml) h=3.5 mm ∅=6mm

Y90-Activity 22 kBq/ml 15 kBq/ml 5 kBq/ml

H3 (0.04 ml) h=3 mm ∅=4mm

• Range of activity

• From 22 to 5 kBq/ml

• Starting from rate acquired, using FLUKA simulation, we could compute the false positive (FP) and false negative (FN) rates under real condition

We require:

FN <5%

FP ~1%

A novel radioguided surgery technique exploiting β-

decays, CHIRONE collaboration, submitted arXiv:1402.2248 [Sci. Reports]

“Battleship” test• Human reaction

• Unlimited time

• Nominal activity 5 kBq/ml

• Single spot activity 0.26 kBq

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Active spots

Not Sure Sure

“Surgeon” one max efficiency

“Surgeon” two max signal/noise

ratio

Optimization of portability

• Portability play a key role

• Real time data analysis

• Easy way to read the signal

• Read-out by custom electronics with wireless connection

• User interface available on tablet

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Timetable

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April 2012

active volume 14 mm3

work outside ✗

read-out 1 fibre!PMT

portability ✗

S/N ✗

Timetable

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April 2012

March 2013

June 2013

September 2014

active volume 14 mm3 6 mm3 11.5 mm3 62.5 mm3

work outside ✗ ✓ ✓ ✓read-out 1 fibre!

PMT1 fibre!PMT

4 fibres!PMT

1 fibre!SiPM

portability ✗ ✗ ✓ ✓S/N ✗ 400

14 cm

1 cm

Timetable

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April 2012

March 2013

June 2013

September 2014

active volume 14 mm3 6 mm3 36 mm3 62.5 mm3

work outside ✗ ✓ ✓ ✓read-out 1 fibre!

PMT1 fibre!PMT

4 fibres!PMT

1 fibre!SiPM

portability ✗ ✗ ✓ ✓S/N ✗ 400 700

Timetable

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April 2012

March 2013

June 2013

September 2013

active volume 14 mm3 6 mm3 36 mm3 196 mm3

work outside ✗ ✓ ✓ ✓read-out 1 fibre!

PMT1 fibre!PMT

4 fibres!PMT SiPM

portability ✗ ✗ ✓ ✓S/N ✗ 400 700 2000

Clinical steps

• Pre-clinical tests:

• on pig meat

• Clinical tests on patients:

• on ex-vivo specimens besides operating room during surgery

• Clinical tests directly on patients:

• Planned with ASMN of Reggio Emilia

• Planned with Istituto Carlo Besta of Milan

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Present work• Develop a large area probe

• CsI(Ti) crystal (2x2x2 mm3) read by SiPM

• Light Yield ~52k γ/MeV

Test the best way to link crystals and optical fibre

Understand how manage the crystals

• Dimension constraint

Test the response of the single crystal

• Improve S/N ratio�30

1 mm !

Thanks for your attention !!!!