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)

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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