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Diagnostic Nuclear Physics in Medicine

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Diagnostic Nuclear Physics in Medicine Thomas J. Ruth UBC/TRIUMF PET Program TRIUMF, Fall 2004 The brain, my second most favorite organ. Woody Allen Goals of the ... – PowerPoint PPT presentation

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Title: Diagnostic Nuclear Physics in Medicine


1
Diagnostic Nuclear Physics in Medicine
  • Thomas J. Ruth
  • UBC/TRIUMF PET Program
  • TRIUMF, Fall 2004

2
Diagnostic medicine tries to look into the body
to see what is happening, in life and in death.
Rembrandt - anatomy lesion
3
How can we probe the human body without a
knife? But first some fundamental ideas that
are needed to understand this topic.
4
Size matters!
How big is Avogadros number 6.02 x 1023? Each
Smartie 1 cm3 or 1 mL 1 mole of Smarties 6 x
1023 mL Assume a truck with a capacity of 90 m3
(10x3x3) 9 x 107 mL The number of trucks needed
6 x 1015 If each truck is 13 m long, that
means that lined up they would be 7.8 x 1013 km
in length or 200 million earth to moon distances.
5
1 grain of salt 0.12 mg 2 x 10-6 moles (or 2
micromoles) 3 x 1017 molecules
This issue will come up later in our discussion
of tracers.
6
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7
Normal chest x-ray
X-ray images produce shadows based on density of
matter.
8
CT image of the brain
9
Magnetic Resonance Imaging (MRI)
10
All of the images shown thus far look at
structure. Many of these images would look the
same in a living person or in a cadaver. What
about function?
11
Why Use PET Imaging?
  • PET imaging is capable of providing quantitative
    information about biochemical and physiological
    processes, in vivo.

12
Tracer Principle
  • Tracer behaves in a similar way to the
    components of the system to be probed.
  • Tracer does not alter the system in any
    measurable fashion.
  • Tracer concentration can be measured.

13
Basic Principles of PET
  • Based on tracer principle.
  • Tracer labeled with positron emitting
    radioisotope.
  • Positron decay.
  • Coincidence detection of annihilation radiation.

14
Positron Annihilation
Positron emitter
Positron range 1 - 10 mm
Neighboring atom
g 2
g 1
Gamma ray range 10 mm - ?
180
15
Positron Emission Tomography
detector 2
g 2
g 1
detector 1
16
PET measures concentration of radioactivity
1) Gamma rays escape from the body Allows
external detection. 2) Two gamma rays are
emitted at 180 when a positron
annihilates The annihilation occurred
somewhere along the line of response (LOR)
between the 2 detectors.
17
PET measures concentration of radioactivity
3) Regions with greater radioactivity levels
produce more LORs Concentration of radioactivity
can be measured and quantified.
18
How do you go from detecting events to an image?
19
Corrections necessary for quantitative PET
(mCi/cc tissue)
  • Scatter correction
  • Attenuation correction
  • Random subtraction
  • Normalization
  • Calibration

20
Fluorodeoxyglucose (FDG)
Glucose
21
FDG Uptake and Retention
Cells
Blood
Glycolysis
Glucose
Glucose
Glucose-6P
FDG
FDG
FDG-6P
22
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23
Focus of the PET Program has been on the Brain
24
The brain, my second most favorite organ.
  • Woody Allen

25
Goals of the Pacific Parkinsons Research Centre
  • Determine the origins of PD
  • Follow natural history of disease (Progression)
  • Develop treatments
  • Control complications of treatment

26
Preliminary epidemiological data
27
Clusters
  • CBC, Vancouver 4/120
  • Community college, eastern BC 4/32
  • Garment factory, Montreal 3/8

200-300 per 100,000 population. 1 in
population aged over 60 years.
28
DA
29
DAT
30
Radiopharmaceuticals
  • Dopamine system
  • 18F-FDOPA
  • 11C-Methylphenidate
  • 11C-Dihydrotetrabenazine
  • 11C-Raclopride
  • 11C-Sch23390
  • NB 11C high specific activities
  • (10 mCi _at_ 10 Ci/mmole 1014 molecules)

31
For PET research you need clever and gifted
chemists!
Photo by Will Brown/courtesy of Chemical
Heritage Foundation
32
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33
Controls
p0.0274
MPTP-exposed
Exposure
1st scan
2nd scan
34
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35
Investigation of disease compensatory mechanisms
Lee et al 2000
36
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37
The importance of isomeric purity.
VMAT2 - 11C-dihydrotetrabenazine
Multiple chiral centres
38
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39
In vivo assessment of endogenous DA concentration
DA
DA
DA
11C-Raclopride
Endogenous DA competes with raclopride for the D2
receptor
40
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41
Apomorphine-induced changes in RAC binding
(putamen)
3
Error Bars 1 Standard Error(s)
2.5
2
1.5
1
.5
0
APO_0
APO_1
APO_2
42
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43
Unlocking the mysteries of the brain!
44
Can you focus this please?
Circa 1976, BNL/UPenn
45
Yes!
  • 25 years later
  • And 100s M

46
Crystal material LSO/LYSO Crystal size 2.1 x 2.1
x 10 mm3
47
UBC/TRIUMF HRRT
48
High Resolution Research Tomograph
  • 119,000 detector elements
  • 4,000,000,000 lines of response
  • gt 1Gbyte of data per image frame

49
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50
Significant Results Beyond UBC/TRIUMF PET FDG
Supply (b-HC!)
18F-
FDG
mPET
PET/CT
Vendor not selected!
51
PET in cancer diagnosis.
RUQ right upper quadrant
52
What have we learned about Parkinsons Disease
thus far?
  • Preclinical changes in PET indices.
  • Asymptomatic patients progress to disease.
  • Early signs of compensation.
  • Singular events can cause parkinsonism.
  • Clusters
  • More evidence of our Event hypothesis including
    progression.

53
Conclusions from Epidemiological Studies
  • Quit working in medical profession
  • Stop all teaching activities and stay at home
  • Eat only organic foods (no pesticides or
    chemicals)
  • Drink plenty of coffee (28 oz per day)
  • Start taking non-steroidal anti-inflammatory
    agents
  • Is this the ultimate formula to prevent PD??

54
Background Radiation
Average population exposure 2.8 mSv/year
0.04
0.005
0.01
0.05
1.0
0.92
0.26
0.01
0.26
0.28
This can vary significantly depending upon life
style and living location.
55
Loss of Life Expectancy Due to Various Risk - Days
  • Being unmarried male - 3500
  • Smoking 2250
  • Heart diseases 2100
  • Being unmarried female 1600
  • Coal Miner - 1100
  • Cancer 980
  • Being poor - 700
  • Stroke 520
  • All accidents - 435
  • Motor vehicle accidents - 207
  • Home accidents - 95
  • Safest jobs 30
  • Bicycle 5
  • All catastrophes combined- 3.5
  • PET scan 1 hour
  • Smoking 1 cigarette 10 min.
  • Pap test (- 4 days)
  • Air bags (- 50 days)

56
Acknowledgements
The contributions of Drs. Jon Stoessl, Doris
Doudet, Raul de la Fuente-Fernadez, Vesna Sossi,
Chong Lee, James Holden and the PET team (Drs.
Mike Adam, Andre Studenov, Jianming Lu, Kelvin
Raywood Salma Jivan, Ken Buckley, Paul Piccioni,
Suzy Lapi, Carolyn English, Caroline Williams,
Shilpa Shah, Jesse McKenzie, Marie-Laure
Camborde, Siobhan McCormack, Arman Rahmim, and
many, many coop students) are gratefully
acknowledged.
57
Acknowledgements
This work has been supported through
contributions from the Canadian Institutes of
Health Research Group grant, Canada Foundation
for Innovation, BC Knowledge Development Fund,
TRIUMF, the Pacific Parkinsons Research
Institute, UBC, and various bake sales.
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