Imaging Techniques Nuclear Medicine

Imaging Techniques

Nuclear Medicine

Patrícia Figueiredo

IST 2010-2011

The wide spectrum of medical imaging techniques

(F. Deconinck, Vrije University, Belgium).

Nuclear medicine imaging

General principles:

• Imaging of the biodistribution of a radiotracer: • composed of a radionuclide incorporated into a molecule whose biodistribution and /or metabolsim is to be studied; • introduced into the body by inhalation, injection into the circulation, oral or subcutaneous administration; • measured by the detection of gamma photons resulting from the radioactive decay of the radionuclide in the radiotracer.

Imaging modalities:

- Planar imaging: Scintigraphy - Tomography: Single photon emission computed tomography (SPECT) Positron Emission Tomography (PET)

Radioactivity and radionuclides

Radioactivity: intrinsic property of isotopes with unstable nuclei (↓A/Z)

Radionuclide: nuclear species of a radioactive isotope (A

-Z)


Radioactive decay: transition to stability by emission of some form of radiation (from parent to daughter nuclide)

Activity [Ci or Bq]: (# disintegrations/time)

Nb. parent nuclides:

Decay constant [s-1]:

Half life [s]:

Biological half life [s]:

Effective half life:



Types of radioactive decay (most common):

1. α emission (210Po, 238Pu, 241Am, 242Cm)

2a. β+ or e+ (positron) emission: p→n+e++ν

2b. or electron capture: p+e-→n+ν

3. β- or e- (electron) emission: n→p+e-+ν~




2b. and 3. → intermediate metastable state

→ 4. Isomeric transition (electron reshuffling)

⇒ γ (X ray ) emission (~10-1000 keV) or emission of Auger electron (~keV) or internal conversion




2a. β+ or e+ (positron) emission: p→n+e++ν ⇒ e+ e- annihilation: e+ + e- → γ + γ

⇒ 2 × γ emission (511 keV,opposite directions)


Interactions of γ rays with matter:

Radiation intensity attenuation:

Linear attenuation/absorption coefficient: µl = µl (ρ, N0, Z , E) [cm-1]

Half value layer: HVL = ln 2 / µl


Radionuclides useful in diagnostic imaging:

- radioactive decay ⇒ monochromatic γ emission

- half life long enough ⇒ distribution within the body

- half life short enough ⇒ minimize radiation dose

- γ energy high enough (>100 keV) ⇒ HVL in tissue > object size

- γ energy low enough (<200 keV) ⇒ minimize scattered radiation

- minimal emission of α and β particles ⇒ minimize radiation dose

- onsite production!


Radionuclides useful in diagnostic imaging:

Single photon emission (for planar imaging and SPECT): Element Radionuclide Chemical Form Half-life γ Energy (keV)

Technetium 99m-Tc various 6.02 h 140

Gallium 67-Ga Gallium Citrate 3.2 d 93, 185, 300, 394

Thallium 201-Tl Thallous chloride 3.0 d 68-82 (X-rays)

Xenon 133-Xe 5.3 d 81

Indium 111-In Indium chloride 2.8 d 171, 245

Iodine 131-I Sodium iodide 8.0 d 364

Positron emission (for PET):


Radionuclide production:

- neutron capture (nuclear reactor)

- nuclear fission (nuclear reactor)

- radionuclide generator

- charged-particle bombardment (cyclotron)

Nuclear fission (nuclear reactor):

x, y: …

Chemical precursor of technetium ~100 MeV


Radionuclide generator (technetium generator):

A metastable radionuclide (99m-Tc, half life 6h) is produced by radioactive decay of a long-lived parent (99-Mo, half life 66h) and extracted by flowing an eluting solution on the surface of the ceramic column with the generator, usually with a periodicity of 12h, 24h or 48h.


Radionuclide generator (technetium generator):

N1: 99-Mo N2: 99m-Tc N3: 99-Tc

equilibrium

→ equilibrium


99m-Tc radiopharmaceuticals (planar imaging and SPECT):

Radiopharmaceutical Short form Clinical Use

Sodium Pertechnetate Na299mTcO4 Thyroid, Salivary Gland and Gastric Scans

99mTc Sulphur Colloid 99mTcS/C Liver, Spleen and Bone Marrow Scan

99mTc Macro Aggregated Albumin 99mTcMAA Pulmonary Blood Flow (Lung Scan)

99mTc Diethylene Triamino Penta Acetic Acid 99mTcDTPA Renal Blood Flow, Function and Excretion (Kidney Scan)

99mTc Methylene DiPhosphonate 99mTcMDP Skeletal Studies (Bone Scan)

99mTc Red Blood Cells 99mTcRBC Cardiac Function and Blood Pool Scans

99mTc Sestamibi 99mTc Tetrofosmin

99mTcMIBI 99mTcTETRO

Myocardial Perfusion (Heart Muscle Blood Flow)

99mTc Hexa Methylene Propylene Amine Oxime

99mTc HMPAO

Brain Scan and Scans for Infection

A chemical ligand is chosen to have high selectivity for the organ of interest with minimum distribution in other tissues and is characterized by: - binding to blood proteins (HSA) - lipophilicity and ionization (membrane transport) - means of body excretion (liver, kidneys)


Radionuclide production through charged-particle bombardment (cyclotron)

D-shaped electromagnets ⇒ axial magnetic field ⇒ negative ions (1 proton, 2 electrons) of hydrogen (~10 MeV) or deuteron (~5 MeV) ⇒ accelerated in spiral trajectory ⇒ beam is extracted from cyclotron by passing it through a thin carbon foil ⇒ electrons are striped off, leaving protons to bombard the stable nuclei of the target


Positron emitting radiopharmaceuticals (PET):

Structural analogues of a biologically active molecule

Instrumentation

The gamma camera

Instrumentation

The gamma camera: collimator

Instrumentation

Collimator: To mechanically confine direction of photons reaching each detector by restricting the acceptance angle, to allow spatial localization of source while minimizing contributions from Compton-scattered photons.

Hexagon pattern (most common):

d/2

t

Instrumentation

Collimator:

Parallel-hole collimator (most common):

Spatial resolution:

z = distance from source to collimator ⇒ R depends on depth in the body z! ⇒ Geometric distortions!!

Geometric efficiency:

↓t ⇒ ↑G ; ↑ d ⇒ ↑G

k = constant determined by geometry (parallel; diverging; converging; pinhole)

L>>t (L~24 mm, t~0.15 - 0.40 mm)

z~10 cm ⇒ R~1 cm; G~0.015%

d t

L

z Front face

Back face

R

The gamma camera: scintillation detector

Instrumentation

Instrumentation

Scintillation detector:

Scintillation crystal coupled with a photomultiplier tube (PMT)

Instrumentation


1 large thallium-activated sodium iodine, NaI(Tl), crystal coupled to an array of ~ 50-100 PMTs

Scintillation crystal: emission of 415 nm photons, 4 eV energy 13% conversion efficiency

Hexagonal PMTs: Efficient packing + PMT centers are equidistant from their neighbors (d ~ 25 – 30 mm)

d

NaI(Tl)

PMT

Instrumentation


Intrinsic spatial resolution R:

-Crystal thickness: ↑δ ⇒ ↑ R, ↑ sensitivity (optimal δ ~ 0.6 cm in NaI(Tl) detector)

-Statistical variability of crystal scintillation:

-Number of PMTs: ↑NPMT ⇒ ↓ R (NPMT ~ 50-100 in NaI(Tl) detector)

-PMT non-linearities: PMT energy responses vary and are non-uniform across face of scintillation camera ⇒ intensity inhomogeneity (corrected by calibration) + geometric distortions

δ Light Spread Function

Instrumentation

The gamma camera: Anger position network and PHA

-Position network: combination of PMT signals to produce 4 output signals: (X+, X-, Y+, Y-) and their sum – z signal.

-Pulse height analyzer (PHA): selection of z within predefined range (~FWHM photopeak)

photo peak

Compton region

lead X ray peaks

FWHM

iodine escape peak

Instrumentation

Energy resolution (photopeak FWHM):

Ability to discriminate between unscattered and scattered γ rays

Energy spectrum for radionuclide/scintillation crystal used (e.g., 99m-Tc / NaI(Tl)): -Photo peak: photoelectric effect in body (140 keV, FWHM ~14 keV, 10%)

-Iodine escape peak: photoelectric effect in crystal (28.5 keV ⇒ 140-28.5 = 111.5 keV)

-Lead X ray peak: photoelectric effect in collimator - lead (75, 88 keV ⇒ 140-88 ~ 52 keV)

-Compton scatter region: Compton scatter in crystal (peak ~ 90 keV ⇒ 140-90 ~ 50 keV)

Broadening due to Compton scatter in body: Pulse height analyzer (PHA) threshold (~15%)

Câmara gama

The gamma camera: CRO or computer!

-Cathode ray oscilloscope (CRO): light flash on screen in position related to scintillation

Scintigraphy

General principles:

Scintigraphy

General principles: - Isotropic photon emission from the body

- Mechanical collimation to position (x,y)

- Crystal scintillation and light generation in a disc centered in (x,y) with a certain width,

with intensity proportional to energy of incident photon and number of photons

- Scintillation light divided among PMTs according to spatial proximity to (x,y)

- Conversion of light to electric pulse at each PMT, proportional to intensity of light

- Combination of pulses in position network and energy selection by Pulse Height

Analyser (PHA)

- Pulse intensities for each (x,y) position are stored to produce a 2D projection image

(projection axis perpendicular to plane of collimator)

Scintigraphy

Image characteristics:

Spatial resolution R:

- Rcollimator: depends on collimator geometry and depth within the body

- Rdetector: depends on crystal thickness, photon energy, number of PMTs

- RCompton: depends on photon energy, depth in body, collimator and PHA

- kfilter: depends on post-acquisition low-pass filtering

(typically, R ~1-2 cm at large depth; R ~5-8 mm near the surface)

PSF

x

detector + collimator geometry

FWHM Compton scattering

tail

Scintigraphy

Image characteristics:

Signal-to-noise ratio SNR: Poisson distribution ⇒ - radiopharmaceutical dose and organ specificity (limited by safety) - scanning time (limited by radiotracer half life and patient comfort) - tissue attenuation (depth within the body, photon energy) - gamma camera sensitivity (crystal thickness and collimator geometry) - gamma camera dead time N is the true count rate (~20% loss) n is the observed count rate - post-acquisition low-pass filtering (to reduce noise levels)

Contrast-to-noise ratio CNR: no background signal ⇒ CNR ~ SNR - some degradation due to Compton scattering - further degradation due to partial volume effects (depend on R) - further degradation (or improvement) as a result of low-pass filtering

Scintigraphy

Part of the Body Example Radiotracer Brain 99mTc-HMPAO

Thyroid Na99mTcO4 Lung (Ventilation) 133Xe gas Lung (Perfusion) 99mTc-MAA

Liver 99mTc-Tin Colloid Spleen 99mTc-Damaged Red Blood Cells

Pancreas 75Se-Selenomethionine Kidneys 99mTc-DMSA

Applications:

Renogram:

Use of a radiotracer that is

excreted through the kidneys

(e.g., 99m-Tc-DTPA) and

acquisition of a series of

images to observe excretion

through the kidneys.

Scintigraphy

Applications:

Single photon emission computed tomography (SPECT)

Configuration:

Rotating gamma camera

- Rotation around 360º

-Circular or elliptical orbit

(to minimize depth in body)

- Continuous or in discrete steps

(to optimize efficiency vs blurring)

-Single or multiple head:

single-head, two-head, three-head

↑ nb cameras ⇒ ↑ sensitivity, ↓ R

- A 3D image is obtained

Single-head gamma camera

Dual-head gamma camera


Basic principles

-Application of tomographic techniques to produce 2D cross-sectional images

using a gamma camera to detect the emission of a radiopharmaceutical (as in planar

imaging) at different positions around the patient.

-Radionuclides and radiopharmaceuticals identical to planar scintigraphy (99m-Tc)

-Scintillation detectors identical to planar scintigraphy (NaI(Tl)-PMT)

-Mechanical collimation similar to planar scintigraphy, but different beam shape

-Image characteristics differ: ↑ CNR, ↓ SNR, ↑ R…


Collimator:

Parallel hole collimator:

Focused, converging (pinhole) collimator:

↑ sensitivity, but more difficult reconstruction


Sensitivity and line spread function (LSF):

Sensitivity depth dependence:

Solid angle of detection ∝ 1/r2 Volume of sensitive area ∝ r2

⇒ Sensitivity is ~ invariant with distance between source and detector

r

d d=0.5 cm r = 10 cm Ω=0.015 %

Fan beam: Convergent transaxially Cone beam: Convergent axially and transaxially


Image reconstruction

Image function = spatial distribution of radiopharmaceutical activity:

Projection at position φ:

Filtered backprojection:

Filtered projection:

x

x’

y’ y

A(x,y)

pφ(x’)

φ



Image function = spatial distribution of radiopharmaceutical activity:

Projection at position φ:


Filtered projection:

x

i

j y

Aij

piφ

φ


Attenuation correction:

Attenuation ⇒ artifacts due to gamma ray attenuation between source and detector

Including attenuation µ(x,y):

Including attenuation µij:

Weighted filtered backprojection:

Attenuation weighting factor:

Attenuation correction methods: -assume µ is spatially uniform and estimate physical dimensions of object (using CT or MRI) - good for brain, not chest. -measure µ spatial distribution (using a transmission scan of a reference activity tube) and use to calibrate - easier with iterative algorithms, but these are slower…


Scatter correction:

Scatter ⇒ significant contributions due to (inevitable) absence of source collimation

Dual-energy window detection method:

-main window: around photopeak with width Wm – photoelectric + Compton contributions: Cm = Cprim + WmCCompton

-sub-window: in Compton region with width Ws – Compton contributions only: Cs = Ws CCompton

⇒ Primary radiation contribution (nb counts): Cprim = Cm - Cs Wm/Ws

The window width ratio Wm/Ws can be optimized by maximizing the SNR after scatter correction (e.g. for 99m-Tc, Wm = 28 keV (~20%) around 140 keV, Ws = 32 keV (~7%), around 120 keV)


Image characteristics Similar to planar scintigraphy – additionally:

Spatial resolution R Approximately Gaussian PSF, with FWHM ~ 1 cm, data matrix ~64x64, 128x128 (14-17 mm for single-head systems, 6-10 mm for three-head systems) ↑ Data matrix ⇒ ↓ R

Signal-to-noise ratio SNR Signal = mean nb counts / Noise ~ standard deviation of photopeak (typically, ~500.000 counts in brain, ~100.000 counts in myocardium) ↑ Data matrix ⇒ ↓ SNR

Contrast-to-noise ratio CNR Ratio of peak nb counts in “hot spot” to mean nb counts in the background (~ 5-6 x greater than planar scintigraphy, due to separation of superimposed sources)

Applications


Part of the Body Example Radiotracer Brain 99mTc-HMPAO

Thyroid Na99mTcO4 Lung (Ventilation) 133Xe gas Lung (Perfusion) 99mTc-MAA

Liver 99mTc-Tin Colloid Spleen 99mTc-Damaged Red Blood Cells

Pancreas 75Se-Selenomethionine Kidneys 99mTc-DMSA

Measurements: Spatial distribution; Extent of uptake; Rate of uptake; Rate of washout

Applications

Brain perfusion: using 99m-Tc-HMPAO (Ceretec) or Neurolite, which pass BBB

⇒ rupture of BBB leads to radiotracer accumulation in diseased tissues

⇒ spatial distribution of radiotracer is proportional to rCBF

⇒ radiotracer accumulates in regions of high rCBF (tumor, epilepsy, stroke,

schizophrenia, dementia, …)


Applications

Cardiac function: using radiotracers that accumulate in myocardium (Tc or Tl-based)

(most common,

myocardial perfusion

– stress test,

to diagnose

myocardial ischemia

and infarct)


Positron Emission Tomography (PET)

Radioactive decay by positron emission

Positron emitting isotopes


Positron emitting radionuclides

Major elemental constituents of biological tissues

1H analog


Basic imaging principle:

External source:

Uncollimated Collimated


Basic imaging principles:

External source Internal source


Basic imaging principles:

Internal source:

SPECT PET

Mechanical collimation Electronic collimation


Basic imaging principle:

- Detection of 2 anti-parallel γ within a certain time window (simultaneity) and along a line of response (LOR) (colinearity – electronic collimation): annihilation coincidence detection (ACD) – to localize annihilation (positron emission) point.


Basic system configurations:

Translations + Rotations: - easily to fulfill uniform sampling requirements ⇒ simple reconstruction - coincidence detection from opposite banks ⇒ limited efficiency

Rotations only: - insufficient linear sampling, resolved by new sampling schemes (e.g., wobbling) -improved efficiency



Complete stationary ring of detectors surrounding the patient (diameter defines the Field-of-View, FOV)

acceptance angle



Each detector element is connected by a coincidence circuit to a set of opposite detector elements (both in plane and axial, ~ half the total number of detectors N/2): ⇒ N/2 fan beam projections per detector



Multilayer scanners: stacks of rings of detectors in spherical or cylindrical arrangements

Instrumentation

Basic components:

-Scintillation detectors (crystals coupled with PMTs, in rings)

-Annihilation coincidence detection circuitry (PHA + coincidence detector)

(+ cyclotron!)

Objectives:

→ optimize spatial resolution (localization accuracy)

→ optimize sensitivity (nb detected annihilations)

Instrumentation

Scintillation detectors:

Desired characteristics for PET:

- High density ⇒ ↑ detection efficiency - High Z ⇒ ↑ detection efficiency - Short scintillation decay time ⇒ ↑ SNR

- Emission wavelength ~ 400 nm ⇒ ↑ sensitivity of PMT - Refraction index ~ 1.5 ⇒ ↑ light transmission crystal to PMT - High relative light output ⇒ ↓ complexity and cost (photon yield per keV)

- Non-hygroscopy ⇒ ↑ compacticity, ↓ complexity and cost -Small crystal size (~1cm) ⇒ ↓ R

Instrumentation


~6.5 mm

~6.5

mm

4

Instrumentation


Block detector of BGO crystals

1 crystal block: 8x8=64 grooves, 4 PMTs

Instrumentation



Instrumentation



Quadrant sharing: each PMT straddles over 4 quadrants of 4 different blocks

⇒ larger PMTs ⇒ ↓ number of PMTs

⇒ ↓ R ⇒ ↑ dead time

Axial coverage ~ 15 cm (brain) ~170-198 cm (whole body)

Diameter ~ 80-90 cm

Instrumentation

Detector rings:

Blocks of detectors arranged in 1 or more rings (up to 48) (e.g., 288 blocks in 4 rings of 72 blocks) ⇒ Millions of LORs are measured

Instrumentation

Detector rings:

Each detector element is connected by a coincidence circuit to a set of opposite detector elements (both transaxially and axially: ~ half the total number of detectors N/2 ⇒ N/2 fan beam projections per detector

Instrumentation

Annihilation coincidence detection circuitry

Detector: PMT electric pulse → PHA logic pulse of length τ → coincidence detector: Summed signal from 2 detectors > thr. ⇒ record line integral between the 2 detectors

2τ = coincidence resolving time

(~12-20 ns)

Instrumentation

Annihilation coincidence detection circuitry


Filtered backprojection

Object function:

Projection:

= total nb of coincidence events detected by the pair of detectors defining line L


Projection

L



Fan beam geometry


Multi-slice: 2D


Multi-slice: 2D

N direct planes N-1 cross planes

2N-1 planes


Multi-slice: 3D

3D vs 2D: ↑↑↑ sensitivity, ↑scatter (due to absence of absorbing septa)

2N-1 planes N2 planes

Reconstrução de imagem

Multi-slice: 3D

Reconstrução de imagem

Multi-slice: 3D vs 2D: L-6-[18F]fluoroDOPA study: ↑SNR

Corrections

Total number of observed coincidences for detector pair i,j:

Cijtrue number of true coincidences

Cijscatter number of scatter coincidences

Cijaccidental number of accidental coincidences

DTL dead time losses

T acquisition time

Fij distribution of detector efficiencies

Corrections

Normalization of detector efficiency:

exposing uniformly all detector pairs to a 511 keV photon source (e.g., 68 Ge source), without a subject in the field of view:

Normalized counts for detector pair i,j:

Normalization factor:

Amean = average counts for detector pairs in the same plane

Corrections

Multiple coincidence:

Combination of a true coincidence with one or more unrelated events ⇒ data need to be discarded ⇒

Dead Time loss (DTL) = Cijmultiple

(depends on the electronics)

Correction method: - multiply Cij

total by correction factor:

Corrections

Random or accidental coincidence:

2 unrelated annihilation photons are emitted from 2 independent sources and are detected within the coincidence resolving time ⇒ incorrectly assigned line integral resulting from the finite resolving time of the coincidence circuitry

Rate of random coincidences for detector pair i,j: Ri, Rj = single count rates of detectors i, j 2τ = coincidence resolving time

Correction methods: -subtract Cij

rand from Cijtotal before reconstruction

-subtract a delayed coincidence measurement (using additional timing circuitry) before reconstruction

Corrections

Scatter coincidence:

1 or both photons resulting from one event suffer Compton scattering with a small enough energy loss / scatter angle, so that they are detected within the photopeak

Corrections

Scatter coincidence:

1 or both photons resulting from one event suffer Compton scattering with a small enough energy loss / scatter angle, so that they are detected within the photopeak ⇒ incorrect position information ⇒ broader tail in line spread function

Correction method: -measure scatter outside patient + extrapolate -tighter inter-slice collimation in multi-ring systems

Corrections

Attenuation correction

The count rate observed is independent of the position of the source along the LOR: it depends on the diameter alone.

Correction methods: -assume µ is spatially uniform and estimate physical dimensions of object (using CT or MRI) - good for brain, not chest. -calibrate data using transmission spatial distribution obtained from external source (ring of positron emitters, e.g. 68-Ge) -estimate µ spatial distribution using X ray transmission and use to calibrate

Corrections

Attenuation correction

Image reconstruction using transmission scan calibration for attenuation correction

Corrections

Attenuation correction using X-ray transmission

Dual-modality imaging: PET-CT

Corrections

Patient table: translation

Corrections

Illustration of standard PET/CT scanning protocol. The patient is positioned on a common specially designed patient table in front of the combined mechanical gantry. First, a topogram is used to define the co-axial imaging range (orange). The spiral CT scan (grey box) preceded the PET scan (green box). The CT data are reconstructed on-line and used for the purpose of attenuation correction of the corresponding emission data (blue box). Black and blue arrows indicate acquisition and data processing streams, respectively.

Dual-modality imaging: PET-CT

Corrections

Iterative reconstruction

Corrections

Iterative reconstruction

A

B

Image characteristics

Sensitivity: number of counts per unit time detected per unit of activity present in a source.

Electronic collimation: coincidence detection records events from a volume defined by the column joining the two detectors

True coincidence count: (empirical formula derived from phantom) k = constant ρ = activity concentration [µCi / cm3] α = probability of photon scattering within the object volume [cm-3] η = detector efficiency [counts / sec] h = slice thickness [cm] d = object diameter [cm] D = ring diameter [cm] (↑D ⇒ ↓ sensitivity)

r

Detector A Detector B


Signal-to-noise ratio SNR: - radiopharmaceutical dose and organ specificity - scanning time - tissue attenuation (depth within the body) - detector sensitivity - post-acquisition low-pass filtering -noise equivalent count rate:

Contrast-to-noise ratio CNR: - no background signal ⇒ CNR ~ SNR - some degradation due to Compton scattering - further degradation due to partial volume effects (depend on R)


Noise equivalent count rate:

After random and scatter coincidence correction:

Doses which lead to concentrations greater than 1 µCi/cc give no improvement in the number of events recorded by the scanner and serve only to increase the dose to the subject.


Spatial resolution

-Rdetector = intrinsic resolution of scintillation detector Rdetector~ crystal diameter/2

- Rpositron = finite distance between positron emission and annihilation Rpositron~rms~1-2 mm (“sphere of uncertainty”: increases with energy)

- Rnoncol = non-colinearity due to slight deviation from nominal angle of 180º → statistical distribution around 180º with FWHM ~ 0.25º ⇒ Rnoncol ~ 1.6 mm (D = 60 cm), 2.6 mm (D = 100 cm).

-krecon = degradation due to reconstruction algorithm (up to 1,5 depends on the method)


Spatial resolution

Positron range and non-colinearity


Partial volume effects

As the resolution degrades, the smaller cylinders progressively show an underestimation of the concentration due to partial volume effects.

Neurotransmitters Oncology

Applications

References

• Webb, “Introduction to Biomedical Imaging”, Wiley 2003. • Cho, “Foundations of Medical Imaging”, Wiley 1993. • Saha, “Basics of PET imaging”, Springer 2005 • Toga and Mazziotta, “Brain Mapping: The Methods”, Academic Press 2002

Imaging Techniques Nuclear Medicine

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