Original Article In vitro autoradiography of carcinoembryonic antigen ...
Digital Autoradiography of Bone-Seeking …...Digital Autoradiography of Bone-Seeking Radionuclides...
Transcript of Digital Autoradiography of Bone-Seeking …...Digital Autoradiography of Bone-Seeking Radionuclides...
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Digital Autoradiography of Bone-Seeking Radionuclides in Human
George Tabatadze†, Brian W. Miller‡, Sergei Y. Tolmachev†
†US Transuranium and Uranium Registries
College of Pharmacy, Washington State University
‡College of Optical Sciences, University of Arizona
6th Asia-Pacific Symposium on Radiochemistry
Jeju Island, Korea, September 17 – 22, 2017
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iQID: ionizing-radiation Quantum Imaging Detector
6th Asia-Pacific Symposium on Radiochemistry – Jeju Island, Korea
Miller BW, Gregory SJ, Fuller ES, Barrett HH, Bradford Barber H, Furenlid LR. The iQID camera:An ionizing-radiation quantum imaging detector; Nuclear Instruments and Methods inPhysics Research Section A: Accelerators, Spectrometers, Detectors and AssociatedEquipment, A767:146-152, 2014.
Ionizing-radiation imaging:
Gamma/X-rays
Alpha particles
Beta particles
Neutrons
Fission fragments
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iQID vs Conventional Autoradiography
iQID
• Real-time dynamic imaging capability
• No temperature control requirements
• Minimal sample preparation
• Automated readout
Extras
• Portable equipment• High detection efficiency
• Low background rate
• Broad sensitivity to ionizing radiation
6th Asia-Pacific Symposium on Radiochemistry – Jeju Island, Korea
Conventional Autoradiography
• Fixed exposure time
• Temperature controlled environment
• Extensive sample preparation• Manual and automated readout
20th Century
21st Century
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iQID: Cross-sectional View
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iQID Specifications
Grasshopper® 3 USB 3.0 CMOS detectors
• 4.1 MP, 2048×2048 @ 90 fps
• 1” CMOS sensor
Optical pixel size
• 19.5×19.5 μm2 pixels with 40 mm diameter intensifier
and 61×61 μm2 using 125 mm diameter fiber-optic
taper
6th Asia-Pacific Symposium on Radiochemistry – Jeju Island, Korea
40 mm diameter
image intensifier
115mm : 40mm
fiber-optic taper
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6th Asia-Pacific Symposium on Radiochemistry – Jeju Island, Korea
Testing iQID Capabilities
- Feasibility Studies -
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252Cf Alpha Particles and Fission Fragments (I)
Cf-252, mBq scale ~100 Bq total, 5 hours acquisition, 40 fps ZnS:Ag screen: Eljen EJ-444 (3.25 ± 0.25
mg/cm2 ZnS:Ag)
Sub-region: ~21.6k counts over 5 hours ~1.2 Bq (32.4 pCi)Centroid coordinate estimate to nearest sub-pixel quadrant (20.7 μm/pixel)
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252Cf Alpha Particles and Fission Fragments (II)
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• Single Event Detection
Fission
Fragment
Alphas
Fission
Fragment
Alphas
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77Lu and 90Y Beta Particles
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Particle Discrimination
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Radionuclide Microdistribution in Bone
- Initial Study -
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Radionuclides of Interest
241Am: Case 0246 - “Atomic Man” – ion
exchange column explosion accident at
Hanford Site (1976)
• 239Pu: CHI-1 (40-004) – plutonium injection
study at Billings Hospital of the University of
Chicago (1945)
• 226Ra: 03-210 – therapeutic radium injection
case (1926)
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iQID Calibration
• Source: 242Pu, 239Pu, 241Am (87 dpm, E&Z Analytics)
• High detection efficiency
Ø115 mm detector: 93.4% (84.9% with background reduction)
Ø40 mm detector: 92.3% (68.9%)
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241Am Distribution in Bone
• Clavicle Acromial End
• Clavicle Shaft
• Imaging time: 64 h
• Surface activity range:
1.4 – 17.0 mBq mm-2
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239Pu Distribution in Bone
• Femur: Middle Shaft
• Imaging time: 408 h
• Surface activity range:
0.001 – 0.014 mBq mm-2
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226Ra Distribution in Bone
• Femur: Distal End
• Tibia: Middle Shaft
• Imaging time: 235 h
• Surface activity range:
0.1 – 4.1 mBq mm-2
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Case 0246: Clavicle (R) Acromial End
Image Processing: ROI Segmentation (I)
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241Am
239Pu 226Ra
Image Processing: ROI Segmentation (II)
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Findings
6th Asia-Pacific Symposium on Radiochemistry – Jeju Island, Korea
• Radionuclide distribution visualized on a micro scale
• Low signal-to-noise ratio
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6th Asia-Pacific Symposium on Radiochemistry – Jeju Island, Korea
Radionuclide Microdistribution: Next Step
- 241Am Case Study -
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Sample Preparation
• Exposure: 241Am chronic inhalation
• Skeleton activity: 29.6 kBq
• Bones: humerus proximal end, humerus proximal
shaft, and clavicle acromial end
• Samples: Plastic embedded 100-μm thick bone
sections
Humerus Clavicle
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241Am Microdistribution in Bone
Humerus: PE Humerus: PS Clavicle: AE
• Counting time: 300 – 1,600 hours
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Image Data Processing
• Raw iQID images were processed using MatLab®
Code (Octave® software) to reduce background
• Cortical and trabecular bone volumes were defined
using Fiji® (i.e. ImajeJ®) software
Before After
Original Image Segmented ROI
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iQID: Surface Activity
• Average surface activity (As): ROI based
• Max. As : 1 mm2 binning & max. pixel value (ImajeJ)
Humerus: PE Pixel size: 1 mm2
BoneSurface activity, mBq mm-2
†Average ‡Max
HumerusPE (188-1) 0.198 0.251PE (188-2) 0.084 0.034PS (189A-1) 0.074 0.031PS (189A-2) 0.074 0.028
ClavicleAE (1003B-1) 0.057 0.033AE (1003B-2) 0.033 0.016
† Counts averaged over original pixel area (816 μm2 or 389 μm2 for large and small detectors, respectively)
‡ Counts averaged over 1 mm2 pixel
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Improved Signal-to-Noise Ratio
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6th Asia-Pacific Symposium on Radiochemistry – Jeju Island, Korea
Moving Toward Microdosimetry
- iQID vs Radiochemistry -
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Radiochemical Analysis
• Bone sections adjacent to those used for plastic embedding were selected for radiochemical analysis
Drying/Ashing
Digestion/Dissolution
Actinide separation
α-source preparation
Actinide measurement
6th Asia-Pacific Symposium on Radiochemistry – Jeju Island, Korea
PE
PS
1-cm sections
PE & PS
DS
DE
Humerus
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iQID & Radiochemistry: Activity Concentration
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Summary
• iQID allows for real-time quantitative
autoradiography at 20-m resolution for 226Ra, 241Am, and 239Pu
• Microdistribution of 241Am in bone was visualized and
quantified
• iQID measurements are within 30% of radiochemistry
results
• iQID is an effective technique for studying the
heterogeneous distribution of alpha-emitters on a
micro scale
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Thank you for your attention!
6th Asia-Pacific Symposium on Radiochemistry – Jeju Island, Korea