Post on 16-May-2015
Nuclear Medicine Imaging (SPECT and PET) Techniques Nuclear Medicine Imaging (SPECT and PET) Techniques and Applicationsand Applications
Youngho Seo, PhD
Center for Molecular and Functional ImagingUCSF Department of Radiology
2/48Outline of This LectureOutline of This Lecture
RadioactivityTypes of decayGamma radiation, source of signals for Nuclear Medicine
Transmission vs. emissionWhat is emission? Study of function and physiologyProduction of radiotracers
How data are acquiredScintillators, photodetectors (e.g., photomultiplier tubes) Gamma camera, SPECT, PET
SPECT acquisitionsCollimation, scatter, attenuation
PET acquisitionsPositron-electron annihilation, coincidence logic
Image reconstructionApplications (Cancer and Musculoskeletal)
3/48Four Forces (Interactions) and Their MediatorsFour Forces (Interactions) and Their Mediators
Okay. Then, electromagnetic force is carried by “photons”. In other words, photons == electromagnetic radiation that involves interactions of leptons (electrons and positrons in most cases). – This is what we are interested in the most for Nuclear Medicine.
Figure from The Particle Adventure (particleadventure.org)
4/48Radioactive DecaysRadioactive Decays
Spontaneous FissionLittle importance in nuclear medicine
Alpha (α) DecayLittle importance in nuclear medicine
Beta (β) Decayβ- (electron) emissionβ+ (positron) emissionβ- (electron) capture
Gamma (γ) Decay: γ (gamma-ray) radiationIsomeric transitionInternal conversion
5/48BetaBeta++ (Positron) Emission(Positron) Emission
These mostly proton-rich (except 124I) radionuclides are used in positron imaging (a.k..a. Positron Emission Tomography or PET, in short).
e
e
e
e
eeee
νννν
++→
++→
++→
++→
++→
+
+
+
+
+
NO
NC
OF
YX
157
158
117
118
188
189
A1-Z
AZ
eeeeννννeeeennnnpppp
6/48Gamma Emission Gamma Emission -- Isomeric Transition (IT)Isomeric Transition (IT)
Isomer: Nucleus with different arrangements
Ground states: The most stable energy states
Excited states: Arrangements are so unstable that there is only a short transient time (less than 10-12 sec) becoming ground states.
Metastable states: Arrangements are unstable, but relatively long-lived (sometimes up to several hours) before becoming ground states.
γ1 (IC)
γ2 (IT)γ3 (IC)
Tc-99m (6 h half-life)142 keV
140 keV
0 keV
7/48Alternative Alternative -- Internal Conversion (IC)Internal Conversion (IC)
Internal Conversion (IC): Energy from excited nucleus is transferred directly to an orbital electron.
When the electron is ejected, the vacancy is filled by an electron from an outer shell followed by characteristic x-ray.
pp
nn
K shell
L shell
x-ray
8/48HalfHalf--LifeLife
Radioactive decay is a random process (Poisson Statistics).
Mother radionuclide -> Daughter (radio)nuclide
NdtdN λ=− /
N: The number of radioactive atoms at time t.λλλλ: Decay constant, Radionuclide-specific
λtλtλtλt0000eeeeAAAAA(t)A(t)A(t)A(t) −
−
=
= teNtN λ0)(
A: Activity = λλλλN
Time required to reduce its initial activity (A0) to a half (1/2*A0)
0.693/λ0.693/λ0.693/λ0.693/λtttt1/21/21/21/2 =
= − 2/1002
1 teAA λ
10/48Imaging Radioactive EmissionImaging Radioactive Emission
Nuclear Medicine (e.g., SPECT) is based on emission data from radioactive materials injected in the body.
Nuclear signals penetrated through the body are detected and reconstructed to form images.
X-Ray Tube
X-Ray Detectors
To Data Acquisition Electronics
Patient with Radioactivity
Transmission‘through’
Emission‘from’
11/48Nuclear Medicine ImagingNuclear Medicine Imaging
Inject Radioactive
Material DetectRadioactivity
12/48Study of Function and PhysiologyStudy of Function and Physiology
Common radiologic imaging (x-ray, ultrasonography, CT, or MRI)Basically transmission imagingMorphological, structural informationThe images in anatomical imaging consist of true physical parameters (e.g., CT number in CT is directly proportional to photon attenuation coefficient in the imaged object.).
Nuclear Medicine Imaging (scintigraphy, SPECT, or PET) Basically emission imagingPhysiologic, metabolic, biochemical information Use of pharmaceutical (physiology or function) chemically labeled with radioactive elements: radiopharmaceutical (or radiotracer)
13/48Production of Radiopharmaceuticals (aka (Production of Radiopharmaceuticals (aka (Radio)tracersRadio)tracers))
Radioactive elements (radionuclides) are produced by:Natural occurrence, but rarelyNuclear reactors (bombarding neutron beams to stable nuclides)Nuclear fission (as a product)Cyclotron (bombarding accelerated charged particles to stable nuclides)
A radioactive compound used for the diagnosis and therapeutic treatment of human diseases.
Radiopharmaceutical = Radionuclide + Pharmaceutical
For example, 99mTc-MDP = 99mTc (radionuclide) + MDP (methylene diphosphonate)
Used in skeletal scintigraphy primarily for detection of neoplasm, infection, or trauma.
18F-FDG = 18F (radionuclide) + FDG (fluorodeoxyglucose) Used in positron emission tomography primarily to diagnose many brain diseases, measure regional brain function, measure myocardial viability, and diagnose or stage a variety of cancers.
14/48CyclotronCyclotron
16/48ScintillatorScintillator
From Wikipedia,A scintillator is a device or substance that absorbs high energy (ionizing) electromagnetic or charged particle radiation then, in response, fluorescesphotons at a characteristic Stokes-shifted (longer) wavelength, releasing the previously absorbed energy. Most scintillators are inorganic crystals. Examples are: NaI(Tl) (commonly used in gamma cameras), BaF2, CsI, BGO (bismuth germanate, commonly used in PET), LaBr3, LuI3, etc.
Incident nergetic particles (photons or charged particles)
Scintillator
Scintillation photons
17/48Scintillation Photon DetectionScintillation Photon Detection
Scintillation photons are detected by photon detectors such as photomultiplier tubes (PMTs).
radioactivephoton
photocathode dynode
dynode
dynode anode
High VoltageTo Electronics
Scintillation photons
18/48Emission TomographyEmission Tomography
Tomography: [Gk tomos section, cut; Gk graphikos, to write] Process of imaging the structures along a plane through the body.
Single Photon Emission (Computed) Tomography (SPECT or SPET)Positron Emission Tomography (PET)
19/48
Image Reconstruction (Backprojection)
TomographicReconstruction
Rotational SPECTRotational SPECT
Data Acquisition(Projection) Projection Data
(Sinogram)
Reconstructed Data(Tomogram)
Data Acquisition
20/48Commercial SPECT(/CT) ScannersCommercial SPECT(/CT) Scanners
GE Millennium VG ADAC Cardio 60 (Philips Medical)
21/48Positron Emission Tomography (PET)Positron Emission Tomography (PET)
BGO or LSO Crystal
Photomultiplier Tubes
Annihilating
Photons (511 keV)
Ring detector modules (crystal + PMT + read-out electronics) will collect angular projections simultaneously.
22/48Commercial PET(/CT) ScannersCommercial PET(/CT) Scanners
SiemensGeneral Electric
24/48CollimationCollimation
To Data Acquisition Electronics
PhotomultiplierTubes
Light GuideNaI(Tl) Crystal
Collimator
Patient with Radionuclide
(View from top/bottom)
25/48ScatterScatter
Scintillation Camera
Scatter Radiation
Scintillation Camera
Imaging Concept
26/48
Photon Attenuation
Scintillation Camera
AttenuationAttenuation
Scintillation Camera
Imaging Concept
28/48Positron Positron ““β+”” EmissionEmission
eenp ν++→ +
ZAX +1.02MeV→Z−1
AY + β+ + ν
γ
β +Z−1AY
ZAX2moc2 =1.02MeV
29/48Examples of Positron Emitters in Nuclear MedicineExamples of Positron Emitters in Nuclear Medicine
Rb82 rubidium from 82Sr generator3
13NH ammonia labeledO −15 water
Tissue Perfusion
F18 fluorodeoxyglucose
C11 palmitate C11 acetate
Tissue Metabolism
30/48PositronPositron--Electron AnnihilationElectron Annihilation
γEγ = 511 keV
γ
Eγ = 511 keV
Positron Emission (e.g., 18F, 11C, 15O)
Electron in object (e.g., cancer cells)
Positron, ββββ+
Electron, ββββ-
31/48Coincidence Logic (Electronic Collimation) Coincidence Logic (Electronic Collimation)
BGO or LSO Crystal
Photomultiplier Tubes
Annihilating
Photons (511 keV)
Energy DiscriminationAnd Coincidence Timing
Electronics
33/48TomographicTomographic (SPECT and PET) Image Reconstruction(SPECT and PET) Image Reconstruction
Tomographic images are generated from projection data using reconstruction algorithms.
Analytic method: Filtered backprojection
Statistical method: Iterative Maximum Likelihood Expectation Maximization (MLEM) or Ordered Subsets Expectation Maximization (OSEM)
34/48
Filter projections removes blurring of backprojection
process
Filter (edge-sharpenprojections prior to
backprojectionFiltered backprojection
Simple backprojection
Filtered Filtered BackprojectionBackprojection (FBP)(FBP)
35/48Iterative Reconstruction Algorithm (MLEM or OSEM)Iterative Reconstruction Algorithm (MLEM or OSEM)
ANALYTIC ALGORITHMS(Filtered Backprojection)
RadionuclideDistribution
ProjectionData
DataAcquisition
RadionuclideDistribution
ProjectionData
ITERATIVE ALGORITHMS(ML-EM)
DataAcquisition
Tomogram
Backprojection(Tomographic
Reconstruction)
Projection(Models image
acquisition process)
Tomogram
Backprojection(Tomographic
Reconstruction)
The tomogram is a mathematical repre-
sentation of the radio-nuclide distribution within the patient
36/48
StoppingConditions
Measured Projection Data
Projector
Attenuation Map
ImageEstimate
Comparator
Corrector
FinalImage
Initial ImageEstimate
Iterative Image ReconstructionIterative Image Reconstruction
37/48Iterative EstimatesIterative Estimates
Iter0
Iter1
Iter2
Iter4
Iter8
Iter1
6
Iter3
2
Iter6
4
Obj
ect
39/48Some of Tumor Specific RadiopharmaceuticalsSome of Tumor Specific Radiopharmaceuticals
RADIOPHARMACEUTICAL18F-fluorodeoxyglucose (FDG)
18F-fluorotamoxifen18F-estadiol11C-choline
11C-methionine111In-octreotide111In-Oncoscint99mTc-174H.64
99mTc-IMMU-4-Fab’99mTc-methylene diphosphonate (MDP)
111In-ProstaScint111In-antiCEA
123I-vasoactive intestinal peptide131I-metaiodobenzylguanidine
TUMOR SITEmost tumors
breastbreast
prostateglioma, lymphoma, lung
neuroendocrine, lymphomacolorectal, ovarian
head/neckbreastbone
prostatecolorectal
lung, stomach, pancreas, colonneuroblastoma
40/48
Glucose
18FD
G
18FDG-6-PO4
Vascular Compartment
Metabolic Compartment
hexokinase
G-6-P
ECFGlycogen
G-1-PO4
G-6-P
F-6-P
CO2 + H20
Glucose
Glu
cose
Cap
illar
y M
embr
ane
18FDG18FDGhexokinase
G-6-P
Phosphorylase 'a'
“FDG, glucose analogue… …FDG-6-phosphate does not undergo glycolysis, and does not enter the fructose-pentose shunt or glycogen synthesis pathway… …cellular FDG uptake reflects the overall rate of transmembranous exchange of glucose…”(Medcyclopaedia provided by Amersham Health)
22--deoxydeoxy--2[2[1818F]fluorodeoxyglucose (FDG) metabolismF]fluorodeoxyglucose (FDG) metabolism
41/481818FF--FDGFDG--PET ScanPET Scan
*Data courtesy of Tom Lewellen, Ph.D., University of Washington
18F-Fluorodeoxyglucose (FDG)
42/481818FF--FLT (FLT (fluorothymidinefluorothymidine) PET) PET
FLT is a cell proliferation marker. The figures show tumor uptake in patient’s tongue.
43/4899m99mTcTc--MDP Bone ScanMDP Bone Scan
Normal Metastatic Prostate Cancer
44/4899m99mTcTc--sestaMIBI SPECTsestaMIBI SPECT
http://www.gehealthcare.com/usen/fun_img/nmedicine/myosight/products/imgcasestudy_new.html
45/48111111InIn--ProstaScint SPECT/CTProstaScint SPECT/CT
46/48
Bone scintigraphy reveals changes in bone metabolism (bone turnover or blood flow) rather than changes in bone structure.
Structural information is not present. So, bone scintigraphy cannot replace any other structural imaging (x-ray radiography, CT, or MRI).Very sensitive (because it reveals the metabolism of the bone), but usually specificity is very low.
However,Can be used (and is primarily useful) for:
Stress fractures (the result of repeated low-level impact) when radiography is normal.Confirmation of fracture when radiography is normal.Infection (osteomyelitis) when combined with gallium scan or radiolabeled white blood cell (WBC) scan.
99m99mTcTc--MDP or 18FMDP or 18F--Fluoride in Musculoskeletal ApplicationsFluoride in Musculoskeletal Applications
47/4899mTc99mTc--MDP to Image Stress FractureMDP to Image Stress Fracture
Pain in the right foot for three weeks caused by stress fracture.
From http://www.uhrad.com/spectarc/nucs012.htm
48/48
Skeletal muscle activity measurements by 18F-FDG PET (glucose metabolism) in runners.
Useful imaging technique for:Sports science and rehabilitation medicineIndex for proper training of a particular muscle group
201Tl-SPECT can be used for a similar application. However,
201Tl, a Potassium analog, is directly proportional to blood flow.It has been reported that blow flow in the leg during strenuous exercise increases corresponding to an increase of cardiac output.
Tashiro M, et al. J Nucl Med. 1999;40:70-76.
Direct Musculoskeletal Measurements by Direct Musculoskeletal Measurements by 1818FF--FDG PETFDG PET