The ratcap conscious small animal pet tomograph
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The RatCAP Conscious Small Animal PET Tomograph. Craig Woody Brookhaven National Lab. EuroMedIm 2006 Marseille, France May 10, 2006. Imaging The Awake Animal.

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The RatCAP Conscious Small Animal PET Tomograph

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The ratcap conscious small animal pet tomograph

The RatCAP Conscious Small Animal PET Tomograph

Craig Woody

Brookhaven National Lab

EuroMedIm 2006

Marseille, France

May 10, 2006


Imaging the awake animal

Imaging The Awake Animal

One wants to study neurophysiological activity and behavior in laboratory animals using PET in order to better understand these effects in humans.

  • 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

C.Woody,EuroMedIm 2006, 5/10/06


Ratcap rat c onscious a nimal p et

RatCAP: RatConscious 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

C.Woody,EuroMedIm 2006, 5/10/06


Tomograph ring

Tomograph Ring

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

APD

(Hamamastu

S8550)

LSO array

Actual RatCAP Ring

LSO

Socket

Readout chip

APD

C.Woody,EuroMedIm 2006, 5/10/06


Readout electronics

Readout Electronics

Custom ASIC (0.18 mm CMOS)

32 channels

preamp, shaper, discriminator

~ 1W total power

ZCD

Bare chip

Totally Digital Output

5 bit address

Leading edge gives timing

No ADC’s

Minimizes cabling

Packaged chip

C.Woody,EuroMedIm 2006, 5/10/06


Energy resolution

Energy Resolution

Threshold scan

Threshold (mV)

Differential pulse height spectrum

Threshold (mV)

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

FWHM ~ 23%

Thresh

C.Woody,EuroMedIm 2006, 5/10/06


Timing resolution

Timing Resolution

2t ~28 ns

Timing resolution is used to

reject randoms background

Coincidence window

2t ~ 2 • FWHM

  • 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

C.Woody,EuroMedIm 2006, 5/10/06


Position resolution

Position Resolution

RatCAP

7 mm

15 mm

FWHM (mm)

R4 MicroPET

Point Source Resolution

3.4:1 activity ratio (striatum to background)

Rat Brain Striatum Phantom

Intrinsic Spatial Resolution

1.28 mm FWHM

Concorde P4 MicroPET

= 1.75 mm

UCLA MicroPET

= 1.58 mm

C.Woody,EuroMedIm 2006, 5/10/06


Sensitivity

Sensitivity

Count Rate (kcps)

4 mCi

2t = 40 ns

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

RatCAP Point Source Sensitivities

0.7% @ 150 kev

0.4% @ 400 keV

C.Woody,EuroMedIm 2006, 5/10/06


Ratcap support system

RatCAP Support System

Weight is completely counterbalanced

(animal feels only inertia)

Inner ring attaches to head which mounts to tomograph

Gimbal ring allows head movement

C.Woody,EuroMedIm 2006, 5/10/06


Adaptation to wearing the ring

Adaptation to Wearing the Ring

Corticosteroid Levels in Untrained rats wearing the RatCAP

Animal training and conditioning should reduce stress levels significantly

C.Woody,EuroMedIm 2006, 5/10/06


Animal training

Animal Training

C.Woody,EuroMedIm 2006, 5/10/06


Mounting the ratcap to the head

Mounting the RatCAP to the Head

C.Woody,EuroMedIm 2006, 5/10/06


Rat wearing the ratcap

Rat wearing the RatCAP

C.Woody,EuroMedIm 2006, 5/10/06


First images

First Images

517 g rat, 802 uCi 18F-FDG i.p. injection

45 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)

MicroPET R4

RatCAP

Overlay

RatCAP FOV

C.Woody,EuroMedIm 2006, 5/10/06


Methamphetamine images using the ratcap

Methamphetamine Images Using the RatCAP

RatCAP vs MicroPET Time Activity Curve

250

200

150

ROI Activity in nCi/cc

RatCAP

MicroPET

100

50

0

0

100

200

300

400

500

600

700

Time in seconds

RatCAP

MicroPET

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

C.Woody,EuroMedIm 2006, 5/10/06


Fluoride scan

Fluoride Scan

Brain

Artifact

( due to randoms correction)

Skull

3 mCi 18F Injection

Uptake mainly in the bone

C.Woody,EuroMedIm 2006, 5/10/06


Summary

Summary

  • 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.

C.Woody,EuroMedIm 2006, 5/10/06


The team

The 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. Fontaine

University of Sherbrooke

C.Woody,EuroMedIm 2006, 5/10/06


Backup slides

Backup slides

C.Woody,EuroMedIm 2006, 5/10/06


Effects of anesthesia

Effects 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

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

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

C.Woody,EuroMedIm 2006, 5/10/06


Effects of anesthesia1

Effects 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

Reduction in glucose metabolism

with isoflurane in humans

Similar effects are seen in the rat

M.Pomper, Johns Hopkins

D.B. Stout et al, UCLA 1998

C.Woody,EuroMedIm 2006, 5/10/06


Neurotransmitter activity in the brain

Neurotransmitter Activity in the Brain

MAO A

DA

DA

11C-Cocaine

DA

DA

DA

DA

DA

DA

DA

DA

DA

DA

DA

DA

DA

DA

DA

DA

DA

DA

signal

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

C.Woody,EuroMedIm 2006, 5/10/06


Readout 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

Readout System

FPGA

C.Woody,EuroMedIm 2006, 5/10/06


Rat wearing the ratcap1

Rat wearing the RatCAP

C.Woody,EuroMedIm 2006, 5/10/06


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

C.Woody,EuroMedIm 2006, 5/10/06


Wrist phantom studies

Wrist Phantom Studies

Artery

Vein

Radial artery

Ulnar artery

1 cm

Planar Image obtained with Wrist Phantom

Wrist Phantom

C.Woody,EuroMedIm 2006, 5/10/06


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