The RatCAP Conscious Small Animal PET Tomograph

The RatCAP Conscious Small Animal PET Tomograph

Craig Woody Brookhaven National Lab

EuroMedIm 2006Marseille, France

May 10, 2006

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Imaging The Awake AnimalImaging The Awake Animal

• Animals need to be anesthetized during PET imaging due to their inability to lie motionless in the scanner• Anesthesia can greatly depress brain functions and affect the neurochemistry that one is trying to study• Cannot study animal behavior while under anesthesia

One wants to study neurophysiological activity and behavior in laboratory animals using PET in order to

better understand these effects in humans.

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RatCAP: Rat Conscious Animal PETRatCAP: Rat Conscious Animal PET

A miniature, complete full-ring tomograph mounted to the head of an awake rat.

• Compact, light weight (< 200 g), low power detector

• Small field of view (38 mm dia. x 18 mm axial)

• Attached to the head of the rat and supported by a tether which

allows reasonable freedom of movement for the animal

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Tomograph RingTomograph Ring

Readout chipAPD

LSO

Socket

LSO array

Ring containing 12 block detectors of 2x2 mm2 x 5 mm deep LSO crystals with APDs and integrated readout electronics

APD(Hamamastu

S8550)

Actual RatCAP

Ring

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Readout ElectronicsReadout Electronics

A 0 A 1 A 2 A 3 A 4

A 0 A 1 A 2 A 3 A 4

C L O C K

C F D

T IMINGE D G E

C HA NA D D R E S S

E D G E +A D D R E S S

T se rial

T c lk

Totally Digital Output5 bit address

Leading edge gives timing

No ADC’sMinimizes cabling

ZCD

Bare chip

Packaged chip

Custom ASIC (0.18 m CMOS)32 channels

preamp, shaper, discriminator

~ 1W total power

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Energy resolution is used primarily for scatter rejection

• Presently have common threshold for all channels• Measure count rate as a function of threshold for all channels and differentiate spectra• Requires setting threshold low enough for good efficiency for lowest channel (~ 146 keV) poor timing resolution for others• Next version of chip will have independent gain and threshold settings for each channel

Differential pulse height spectrum

Threshold scan

Threshold (mV)

Threshold (mV)

Energy ResolutionEnergy Resolution

FWHM ~ 23%

Thresh

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• Large background from activity in the rat’s body • High singles rate (~ 50 KHz/block)• Not possible to shield background due to added weight• Next version of chip will use a leading edge discriminator and time-over-threshold measurement ( energy) for time walk correction and improved timing resolution

Timing ResolutionTiming Resolution

Timing resolution is used to reject randoms background

Coincidence window2 ~ 2 • FWHM

2~28 ns

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Position ResolutionPosition Resolution

Rat Brain Striatum Phantom

Spatial Resolution vs. Radius

0

1

2

3

4

5

0 2 4 6 8 10 12 14 16 18

radius (mm)

FWH

M (

mm

) FBP no arcFBP tangFBP rad3DML tang3DML radF

WH

M (

mm

)

R4 MicroPET

RatCAP7 mm

15 mm

Point Source Resolution

Intrinsic Spatial Resolution

1.28 mm FWHM

Concorde P4 MicroPET = 1.75 mm

UCLA MicroPET = 1.58 mm

3.4:1 activity ratio (striatum to background)

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SensitivitySensitivity

RatCAP Point Source Sensitivities

0.7% @ 150 kev0.4% @ 400 keV

Small Animal PET Sensitivities(Threshold = 250 keV)

microPET (original) 0.56%ATLAS 1.8%microPET R4 4.4%microPET P4 2.3%microPET II (proto) 2.3%microPET Focus 220 3.4%microPET Focus 120 7.7%

microPET R4 = 45 kcps @ 6 uCi/cc

Count Rate Performance

0

5

10

15

20

25

30

35

40

0 2 4 6 8 10Activity (Ci/cc)

Cou

nt R

ate

(kcp

s)

NEC (2R)TrueRandom

Co

un

t R

ate

(kc

ps)

4 Ci2 = 40 ns

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RatCAP Support SystemRatCAP Support System

Weight is completely

counterbalanced(animal feels only inertia)

Gimbal ring allows head movement

Inner ring attaches to head which mounts

to tomograph

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Adaptation to Wearing the RingAdaptation to Wearing the Ring

0

3500

7000

NormalRat

Control RatCAP NormalRat

Control RatCAP

10 AM (1 hr) 2 PM (4 hr)

Pla

sma

CO

RT

(n

g/m

L)

Corticosteroid Levels in Untrained rats wearing the RatCAP

Animal training and conditioning should reduce stress levels significantly

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Animal TrainingAnimal Training

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Mounting the RatCAP to the HeadMounting the RatCAP to the Head

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Rat wearing the RatCAPRat wearing the RatCAP

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First ImagesFirst Images

MicroPET R4

Overlay

RatCAP

517 g rat, 802 uCi 18F-FDG i.p. injection45 min awake uptake,

then chloral hydrate euthanasia

MicroPET R4 scan• 10 min, LLD = 250 keV, 2 = 10 ns• 3D MLEM (20 iterations)

RatCAP scan• 33 minutes livetime over 150 min scan

– equivalent to 1.9 X decays of R4 scan• Monte Carlo-based 3D MLEM

– 200 iterations– Randoms correction– No efficiency correction (yet)

RatCAP FOV

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Methamphetamine Images Using the RatCAP Methamphetamine Images Using the RatCAP

RatCAP

The resolution of the RatCAP is slightly better than the commercial MicroPET scanner

MicroPET

RatCAP vs MicroPET Time Activity Curve

0

50

100

150

200

250

0 100 200 300 400 500 600 700

Time in seconds

RO

I A

ctiv

ity

in n

Ci/

cc

RatCAPMicroPET

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Fluoride ScanFluoride Scan

3 mCi 18F InjectionUptake mainly in the bone

Brain

Skull

Artifact ( due to randoms correction)

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SummarySummary

• The ability to image the awake animal will open up many new possibilities in neurophysiology and neurochemistry

• The RatCAP is a fully functional miniature 3D tomograph that can be used for PET imaging of live, unanesthesized rats, and will provide one of the first opportunities to perform detailed studies on awake animals

• The device can also be used as a standard small animal tomograph for anesthesized animals, and can be used for other applications using the same detector components

• The first preliminary studies using the RatCAP have been completed, and we are now looking forward to the first real awake animal images and to improving its design in the future.

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The TeamThe Team

P. Vaska, C. Woody, D. Schlyer, J.-F. Pratte, P. O’Connor, V. Radeka,

S. Shokouhi, S. Stoll, S. Junnarkar, M. Purschke,

S.-J. Park, S. Southekal, V. Dzhordzhadze, W. Schiffer,

D. Marsteller, D. Lee, S.Dewey, A. Villanueva, S. Boose,

A. Kandasamy, B. Yu, A. Kriplani, S. Krishnamoorthy, S. Maramraju

Brookhaven National Laboratory

J. Neill, M. Murphy, T. Aubele, R. Kristiansen

Long Island University

R. Lecomte and R. FontaineUniversity of Sherbrooke

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Backup slidesBackup slides

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Effects of AnesthesiaEffects of Anesthesia

• Blood flow and metabolism depend on type and dose of anesthesia

• Global and regional cerebral blood flow is affected by anesthesia

• Cerebrovascular reactivity to CO2 is perturbed

• Neural activity is suppressed

• Effects are different for different animals and species

M.Pomper, Johns Hopkins

The effect of anesthesia on the uptake of β-CFT on dopamine transporters in the monkey brain.

From the 9th International Conference: Peace Through Mind/Brain Science, Hamamatsu, Japan, Jan. 30-31, 2002

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Effects of AnesthesiaEffects of Anesthesia

• Blood flow and metabolism depend on type and dose of anesthesia

• Global and regional cerebral blood flow is affected by anesthesia

• Cerebrovascular reactivity to CO2 is perturbed

• Neural activity is suppressed

• Effects are different for different animals and species

M.Pomper, Johns Hopkins

Reduction in glucose metabolism with isoflurane in humans

Similar effects are seen in the rat

D.B. Stout et al, UCLA 1998

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Neurotransmitter Activity in the Brain Neurotransmitter Activity in the Brain

Drugs like cocaine can block the re-uptake sites for neurotransmitters like dopamine which upsets the normal equilibrium and can cause effects of addiction

DA

DA

DA

DA DA

MAO A

DA

DA

signal

DA

DA

DA

DADADA DA

DA

DA DA

DA

DA

DA

11C-Cocaine

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Readout SystemReadout System

Time Signal Processing Module• FPGA time stamps and packages

singles events into 64 bit words• 1.3 ns bit resolution

VME data acquisition• VxWorks running PDAQ• Up to 40 MB/s to Linux box

Online monitoring• Singles & coincidence rates

Offline processing• Time and energy calibrations• Coincidence sorting• Randoms estimation• Efficiency normalization• Sinogram sorting FPGA

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Rat wearing the RatCAPRat wearing the RatCAP

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Wrist Scanner for Measuring the Arterial Input Function Wrist Scanner for Measuring the Arterial Input Function

Obective: to perform non-invasive quantification of the Arterial Input Function using PET Imaging.

Activity in the surrounding veins produce a significant background which can be rejected using the good spatial resolution from PET

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Wrist Phantom StudiesWrist Phantom Studies

Radial artery Ulnar artery

Wrist Phantom

Artery Vein

Planar Image obtained with Wrist Phantom

1 cm