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