precise timing for medical devices

Science for Peace the World Over Erice August 2016

Precise Timing for Medical Devices

Crispin Williams - INFN Bologna and CERN

New Manhattan Project - Science for Peace the world over

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Medical imaging• Conventional imaging: X-ray, CT scans, MRI

• Molecular imaging: PET, SPECT

PET (Positron Emission Tomography) scanners create images of the distribution of positron emitters in the body of subjects under investigation. PET scans have a fundamental advantage over other forms of medical imaging, such as CT scans; since they are sensitive to the functioning of biological processes. Biomarkers interact chemically with their surroundings and will alter the image according to molecular changes occurring within the area of interest. Since the imaging technique operates at the cellular level of the body, it is known as molecular imaging. The ability to image fine molecular changes opens up an incredible number of exciting possibilities for medical application, including early detection and treatment of disease and basic pharmaceutical development.

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Positron Emission Tomography

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Nucleus of marker atom

e+

e-

511 keV photon

511 keV photon1 to 2 mmLine of response


Radio-tracers• Glucose with 18F replacing hydrogen [18F]FDG

half life: 110 minutes

• 15O - water - half life: 122 sec

• 13N - ammonia - half life: 10 min

• 11C - acetate + others - half life: 20 min

• 82Ru (chemically similar to potassium) half life : 72 sec

• 68Ga - half life: 68 min

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Some examples of use of PET imaging

• Scans for tumours using [18F]FDG, especially for staging and studies of efficacy of medication. Not so good for slow growing tumours (such as pancreas and prostrate)

• Strokes: need whole body PET scan to find the blood clot source: marker sensitive to Fibrin

• Arthritis: study of inflammation: medication is expensive and is needed for the life of the patient

• Alzheimer’s : Study of the disease and medication

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Hodgkin's lymphoma

before chemotherapy

after chemotherapy

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Scan of brain using marker sensitive to amyloid-β (11C Pittsburg compound B)

Control group

Alzheimer’s

The good news: studies show that people who use their brains (writing memos and emails for example) inhibit

the formation of amyloid-β

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targets of this project

• Clearer images using a lower dosage of radio-tracer

• Direct measurement of tracer uptake by dynamic imaging

• Better motion compensation

• images produced online - less patient recall

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Factors affecting PET image• range of positron before annihilation (1-2 mm)

(this limits the spacial resolution)

• Two 511 keV photons not exactly back-to-back(important that the detectors are mounted close to the subject being scanned)

• Quantitative imaging(exact attenuation maps)

• slow reconstruction of image

• background

• slo

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Image reconstructed from lines of response (LOR)

We do not know the location along the line

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Background

• need multi-pass analysis of data to form image: lengthy and leads to patient recall

• weak signal hard to discern

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Time of flight : localise the positron along LOR

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Advantages of Time-of-flight PET imaging

• reduced background - clearer images

• PET image is corrected with an ‘attenuation map’ to get quantitative data. TOF-PET not so critical on ‘attenuation map’

• Artefacts created by multi-pass analysis: TOF PET has far fewer artefacts.

• Motion compensation much easier with TOF-PET

• Opens up possibility of Dynamic Imaging

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The detector• high detection efficiency for 511 keV photons

(high fraction of photo-effect interactions - rather than Compton scattering ( i.e. high Z material)

• Very precise timing of arrival of 511 keV photon (Coincidence Time Resolution < 100 ps FWHM : equivalent to 16 mm length along LOR)

• detector material is a block of crystal : need to locate photo-electric interaction to ~ 1 mm in 3D inside crystal

• insensitive to magnetic field ( MRI scanner nearby)

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Conventional crystal readout• readout cell matched to

each crystal - position resolution defined by crystal cross section

• No depth of interaction- impacts position and timing

• some problems coupling of read-out cell to electronics

Matrix of MPPCs

Array of scintillating crystals

Depth of interaction

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The new detector geometry• photosensor

fabricated as strips - with readout at each end

• Crystal arranged as slabs

• Precise position determination - including depth of interaction

• each ‘light puse’ viewed by many independent sensors: this leads to improved timing

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STRIP SiPM

511 keV gamma

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mm

11 mm

3 mm

18 mm

Interaction point


MPPC strips have been developed by us at Hamamatsu

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Prototype tests

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22Na Source

3 x 3 x3 mm3 LFS crystal

Slab LFSwith Strip MPPC

plotEntries 1357Mean 2746RMS 87.58

/ ndf 2χ 24.89 / 23Constant 5.4± 152.7 Mean 2.4± 2744 Sigma 1.73± 82.41

2200 2400 2600 2800 3000 3200 3400

Entr

ies

0

20

40

60

80

100

120

140

160CTR

Entries 1357Mean 2746RMS 77.58

/ ndf 2χ 24.89 / 23Constant 5.4± 152.7 Mean 2.4± 2744 Sigma 1.73± 73.63

FWHM=173 ps

Time difference (ps)

D4TEntries 90235

Mean 2.146e+05

RMS 2.919e+04

0

200

400

600

800

1000

1200 Entries 90235

Mean 2.146e+05

RMS 2.919e+04

Na 22 ToT left

Entr

ies

ToT (ns)150 200 250 300 350

511 keV photopeak

D4PEntries 91671

Mean 2.311e+05

RMS 3.353e+04

0

200

400

600

800

1000

1200Na 22 ToT right

Entries 91671

Mean 2.311e+05

RMS 3.353e+04

Entr

ies

ToT (ns)

150 200 250 300 350

511 keV photopeak

need to move on from small prototypes to a system


System aspects

• Important to surround the subject being scanned

• Building a large high resolution (spacial and timing) much more difficult than lab tests of small detector elements

• Must have system capable of very high data flow

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example: PET scanner of head

• important to have module under the chin

• high sensitivity requires large coverage

OPTICAL FIBER DATA CABLES

100 MHz MASTER CLOCK

POWER

WATER COOLING

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module


modules

• Building a large high resolution (spacial and timing) much more difficult than lab tests of small detector elements

• Integrate electronics into detector modules Two important electronic developments: SAMPET and SuperNINO

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complete system• modules mounted

close to subject

• high bandwidth data processing needed

• Online reconstruction of image - (a) uptake measurements: less patient recall

Computer cluster for4D reconstruction

Computer for dynamic image reconstruction

~ 100 m

4.8 Gb/s optical fibres

Dynamic online display

optical fibre connection

All elements are parts of large particle physics experiments

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so… key points of the project: build two (or more) modules with complete

readout• Coincidence time resolution (CTR) less than 100 ps FWHM

• High sensitivity - precise position measurement

• unique geometry for photosensor - the strip MPPC

• unique geometry for crystal detectors - segmented slabs

• unique front-end electronics designed for precise timing: SuperNINO

• unique TDC - high rate, high precision (5 ps) designed to be coupled to SuperNINO

• system designed for high rate - low dead time - online reconstruction

• Consortium of groups eager to work on this project

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Consortium• INFN (Bologna): SuperNINO, Strip MPPC, mechanics, project

management

• CERN: Strip MPPC, central laboratory

• Orsay: SAMPET TDC

• Saclay: SAMPET and on-detector analysis, data transfer

• Ketek (SME) to produce a European version of Strip MPPC

• Geneva University hospital: image reconstruction, display, phantom tests

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What we need

• Funding for equipment: crystals, photosensors, SuperNINO, SAMPET, data-links, computers, mechanics, etc

• Funding for personnel : post-doc positions, PhD positions

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Summary• PET sensitive to molecular composition: known as molecular

imaging

• Big improvements can be made with the image (reduce background, reduce artefacts)

• These improvements will allow measurements of uptake of radio-tracers: essential tool to distinguish tumours from inflammation

• Higher sensitivity allows lower dosage of radio-tracers

• High bandwidth data acquisition needed: improved sensitivity - allows use of short lived radio tracers.

• Truly inter-disciplinary project with many detector developments borrowed from particle physics

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Science for Peace the World Over Erice August 2016 27

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precise timing for medical devices

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