Imaging and data

acquisition in Radiotherapy
Michael Trainer
• Wide range of imaging techniques are
used for every patient:
– Diagnosis (CT, PET, MR, plane x-rays)
– Treatment planning (CT possible MR/PET fusion)
– Follow-up (all above + on-line cone beam imaging)
• Use of images is vital for defining tumour
location in relation to normal anatomy
• Sophisticated imaging techniques (PET,
MR etc.) allows better target definition,
leading to better therapeutic ratio
 Plane X-rays
• Simplest imaging is plane X-rays.
– Diagnosis (part of imaging protocol)
– Verification (kV and MV)
– Prescribing (generally palliative treatments)
• In brachytherapy we use films to check
radioactive sources have appropriately inserted
in terms of tumour/organ at risk proximity.
• For MV treatments the clinician can draw on film
the area they wish to treat.
– Simulators are generally used in this centre as a more
advanced technique.
 Simulators
• Diagnostic quality x-ray machine mounted on rotating
gantry
• Radiographic and Fluoroscopic images used for:
• Tumour and normal tissue localisation
• Treatment simulation and verification

Simulator mimics treatment

linac mechanics and field
geometry
Simulator image of thorax
• Wires define jaw positions
on linac showing beam’s
eye view.
• Central cross shows central
axis and/or isocentre.
• Can use fluoroscopy to
observe motion of
tumour/adjacent anatomy,
particularly for lungs
• Gradations mark cm at
100cm from radiation
source (enable check of
magnification).
 Data requirements for planning
• Depends on type of treatment
– Single field
• Field size
• Position
• Prescribe to Dmax- depth of maximum dose
– Parallel opposed pair
• Inter-field distance
• Prescribe to mid-plane
– Multi-field
• 3D patient geometry
• Density information?
• Prescribe to centre of target volume
Computerised Tomography
• A CT data set enables
more accurate
definition of the tumour
volume.
• Rotating anode.
• X-rays collimated into
fan beam and detected
by curvilinear array.
• Rotations can occur in
approx 0.5s.
 Computerised Tomography
• A CT data set made up of transverse slices
through the patient with defined slice thickness
and slice separation (e.g. 0.25–0.50 mm).
• Data is reconstructed into pixels approx.
0.5mmx0.5mm.
• The linear attenuation coefficient μ for each
pixel is compared to that for water and gives us
the CT number (Hounsfield units):

CT number  1000(t  w)/w

• CT numbers give us the electron density
of the material. Compton attenuation is
proportional to electron density.
– CT numbers enable more accurate dose
calculations when using a heterogeneous
algorithm.
– This is of particular use for certain sites eg.
lung, oesophagus oral/nasal cavity etc.
• CT images are geometrically correct.
– Partial volume effects of the bone can be a
problem.
 CT – density information
• CT data provides a
measure of electron
density
• CT number is
calibrated by
scanning a range of
phantoms with known
electron densities,
and creating a CT –
density calibration
curve
CT slice of lung tumour
 CT - Defining tumour volume
• Tumour volume is outlined
manually in each slice
• Volume is expanded in 3
dimensions to give PTV
• The margins for expansion are
based upon estimates of:
– Microscopic tumour
extension (not seen)
– Physiologic motion
– Uncertainty of patient
positioning between
fractions
– E.g. 1.5cm for bladder
 Also need to identify organs at risk
• e.g. spinal cord
• Can use cord position from
lateral radiograph
• Can manually outline cord on a
series of CT slices, and add a
margin to create the PRV
(Planning organ at risk volume,
ICRU 62)
• This can then be used visually
and dosimetrically to aid
planning beam directions and
field sizes
• Radiographic markers are placed at points corresponding to tattoos
on the patient surface
• These points on the CT scan are lined up and defined as the patient
origin
• The position of the treatment isocentre can then be quantified as a
displacement relative to this point, and used for lining the patient up
to isocentre at the time of treatment
 Digitally Reconstructed
Radiographs (DRRs)
• Using portal imaging (either electronic or
film) during treatment is a way of being
confident of treatment position.
• The images can be compared to those
from the simulator if the treatment has
been planned on the sim.
• For a CT planned treatment, DRRs are
created by the planning system using the
CT data set.
Orthogonal DRRs for a Prostate
treatment
 Variations: Cone-beam CT
• Acquires a volumetric 3D
data set in a single
rotation around the
patient
• Multiple kV radiographs
are acquired and back
projected to give the
volumetric data
• High resolution in all axes
• Increase in noise in the
image due to detector
geometry
 Magnetic Resonance Imaging

• Field strengths of 0.2 to 3T commercially available.

 Pros and Cons of MRI
• Offers improved delineation of some
tumours.
• Used in some centres as primary data set
but prone to geometric uncertainty and
may need distortion correction.
• Often used when “registered” or “fused”
with CT so that CT numbers can be used
for planning.
• Partial volume of fat can be a problem.
MRI showing
good
delineation of
glioblastoma
multiforme
Registered MR and CT images
 Positron Emission Tomography
(PET)

• Fluorodeoxyglucose (FDG) is most commonly used as

the body does not distinguish it from glucose
(T1/2=110mins).
• Positrons emitted via β+ decay.
• Highly metabolic areas of the body take up the FDG.
 • β+ annihilated by e-
within 1mm of emission
point.
511 keV
• 2 x 511keV photons
released in opposite
18F(b+)
directions to conserve
momentum.
• Ring of 20x30mm
511 keV detectors.
• Detectors pick up
simultaneous photons
20/30mm BGO and reconstruct where
photons were released.
 • PET shows
physiological function
at a metabolic level.
• Brain always “hot” as
high metabolism.
Whole • Tumours shown in
body lower neck and liver.
18
FDG
(NS-1/13)
PET fused with CT data set
• Most common
systems are now
PET-CT so we have
anatomical
information fused
with PET.
• Lung tumour clearly
visible.
 Data Acquisition for Treatment
Planning
• Whether manually calculating a dose or
using a treatment planning system we
need to know the characteristics of the
radiation beam for each linear accelerator.
• Beam profiles, Percentage Depth Doses
and Tissue Standard Ratios are collected
using a small (0.6cc), waterproof thimble
ionisation chamber and a water tank.
 Water Tank
• 3 orthogonal bars enable
chamber to be moved to
any part of the water tank.
• Chamber position driven
automatically using
computer software.
• Reference chamber placed
in beam above tank
enables measurements to
Chamber placed be corrected for variation in
here beam output.
 Percentage Depth Dose for 6MV,
10x10 beam
11000
10000
9000
8000
7000
6000
Arbitrary
5000
scale 4000
3000
2000
0 2 4 6 8 10 12 14 16 18 20 22 24 26 28
Depth (cm)

• Comparison of PDD with other machines confirms

beam energy and ability to transfer patients
between linacs.
 Beam Profile
14000
12000
10000
8000
Arbitrary scale
6000
4000
2000
0
-18 -15 -12 -9 -6 -3 0 3 6 9 12 15 18
Distance from central axis (cm)

• Modelling of beam profiles within treatment

planning system enables accurate off-axis
dose calculations.
Tissue Standard Ratios (TSRs)
• TSRs are a measure of dose at the isocentre
compared with that for a 10cm x 10cm field at
10cm deep.

• 10cm was chosen as our reference depth

because it is a typical treatment depth.

• We use a water tank to measure TSRs, keeping

our ionisation chamber at the isocentre position,
but varying the depth of the water and field size.
 Measuring TSRs

chamber chamber

e.g.
depth=5cm depth=10cm depth=15cm
FSD=95cm FSD=90cm FSD=85cm
TSR=1.189 TSR =1.000 TSR=0.829

Examples given are for 6MV, jaw size 10cm x 10cm.

Introduction to 4D-CT
 Outline
• Limitations of 3D-CT

• How does 4D-CT work?

• What are the necessary patient criteria?

• What are the potential problems?

• How can we use it?

• What are the associated advantages / disadvantages?

 What are the limitations of the current (3D)
lung scanning technique?
• Provides only a ‘snapshot’ image
of the patient anatomy

• No knowledge of respiratory
motion

• Motion artefacts

• Uncertainties in target delineation

and dose calculation

• Need large margins to ensure

coverage →increased toxicity
 How does 4DCT work?

• Scan projections binned according to breathing cycle

– gives 10 CT datasets, each showing the anatomy at a
different point in the breathing cycle

• Patient scan lasts longer (~90s)

• Exclusion criteria
– Irregular breathing signal
– Large amplitude motion (>2cm) of small tumour (<1cm)
How does 4DCT work?
• Use respiratory surrogate
to establish breathing
signal

• Bins the signal into 10

phases, each
representing a different
point in respiratory cycle

• Reconstructs 10 CT
datasets
+ time-weighted average
+ maximum intensity
projection (MIP)
 What information does 4DCT give us?
• ‘MIP’ tells us the extent of
tumour motion throughout the
respiratory cycle

• ‘average’ allows accurate dose

calculation

• Could also be used for gating

 4DCT in SBRT
• SBRT treatments have a very high dose per fraction,
typically 60Gy in 5#

• 4DCT is extremely useful for SBRT patients due to the

accelerated dose regimen

• Reduced Target margins

• More accurate delineation of OARs

• More accurate dose calculation

How we can use 4DCT?
• Delineate ITV (internal target
volume) from MIP image

• Transfer to ‘average’ image for

accurate dose calculation

• Customise margins (PTV

expansion now based solely on
setup accuracy)

• 4DCT is useful for all patients in

whom respiratory motion is a
concern, e.g.
– IMRT patients
– Large amplitude of motion (i.e.
near diaphragm)
 IR(ME)R Justification
• Extra dose from a 4DCT Scan

• 11mSv (3D) → 15mSv* (4D)

• Results in a 1 in 5000* increase risk of a secondary Cancer

• Use of 4DCT scans therefore needs to be properly justified by an

IR(ME)R practitioner

• Clinical benefit!!!!!!!!

• Re-scans????
*Based on calculations made by North West Medical Physics
 What can go wrong with 4DCT?
• Wrong ‘pitch’ can be set
– Insufficient data collected
– Let patient settle prior to scan
– Check correct pitch selected at end of
scan

• Irregular breathing
– Observe breathing signal during
acquisition
– Inaccurate reconstruction

• Look for discontinuities in anatomy,

unusual features. Consult clinician if
necessary.

• Should rescan with 4DCT if patient can

breathe regularly but has momentary
irregularity

• Should NOT rescan with 4DCT if

patient is unable to breathe regularly for
prolonged period of time (i.e. >2-3
mins)
 4DCT Artefacts
• Breathing signal irregular
during a section of the scan

• Motion artefact at this position

in the image -predicted before
reconstruction

• 0% phase image

• Discontinuities in the patient’s

anatomy

• Integrity of the average image

will be compromised
 What is the impact of 4DCT?
Advantages Disadvantages

• More realistic representation of • Increased patient dose

the patient – 15mSv Vs 11mSv
– more accurate dose
calculation
• Not suitable for all patients
– scan won’t reconstruct from
• Reduced motion artefacts irregular breathing pattern

• Customised margins for each • Negative impact on resources

patient – takes longer
– ‘ensures’ target coverage – requires more training

• Potential for reduced margins

may allow reduced toxicity
 Other solutions
• Gating (using 4DCT)

• Coached breathing

• Breath-hold techniques

• Tumour tracking

• 4D-CBCT
Current and future use of MRI and
PET in radiotherapy treatment
planning
 Lecture
• Current use of MRI and PET in treatment
planning
– MRI – delineation brain tumours
– PET – NSCLC
• Future uses;
– Equipment development and considerations
– MRI – Spectroscopy, Diffusion
– PET – alternative tracers, PET/CT
• Current study PET tracers – hypoxia,
proliferation
 Introduction
• Move towards conformal treatments and
individualised treatments
– IMRT
– Hyper/Hypo-fractionation schemes
– Using individuals tumour radiobiology
– IGRT
 Introduction – current use of MRI
and PET in treatment planning
• MRI
– Image fusion for brain patients – main benefit
is improved soft tissue contrast

• PET
– Non-small cell lung cancer (NSCLC) patients
 MRI in treatment planning
• MRI for delineation in brain tumours
– Recommended by the Royal College of Radiologists
(selected sites)
– Gd contrast also beneficial
• MRI studies show less inter-observer difference in
delineation
• Complementary imaging
– MRI soft tissue boarders + bone marrow invasion
– CT tumour fat boarders and bone cortex invasion
• Still need CT for good heterogeneity correction
– MRI no automatic/easy method of getting electron
density
 MRI in treatment planning

• Image distortion
– From non-uniformities in magnetic field and non-
linearity in applied gradients
– Shim coils can help

• Image fusion
– Immobilise head and neck
– Neck flexion, head position relative to shoulders,
independent mandible movement
 PET in radiotherapy treatment
planning
• 18FDG-PET scans
– Glucose analogue, provides metabolic information
– Complements CT (and MRI)
– Not tumour specific
• PET/CT most common
• False positives, brown fat uptake etc
• NSCLC – where PET is most commonly used
– Distinguishes benign regions - atelectasis (collapsed lung)
– Nodal involvement and distance metastases
(Better staging)

• Less inter-observer error in GTV definition

– Uptake seen in areas larger than 1cm (PET resolution
~5mm)
– Can appear fuzzy as integrated over breathing cycle
Radiotherapy Treatment
Planning
PET in radiotherapy treatment
planning
PET in radiotherapy treatment
planning
Future use of MRI and PET in
treatment planning
Potential use of MRI in treatment
planning
• Equipment issues;
– Cost
– Suitability of patients
– Scan times
– Field strength
• better resolution, contrast, SNR
• (or more patients)
• (possible European legislation of static and RF
fields)
1.5T vs. 3T
 MRI Spectroscopy

• Measure signal from magnetic nuclei -

H1
• Signal depends on local magnetic field
– H1 produce different signal depending on
bonding
• Provides biochemical information where
little morphological difference may exist
– Distinguish malignant/benign tissue
– Distinguish different tumour types
– Evaluate response and/or recurrence
 MRI Spectroscopy – very simple
explanation
• Spins align to magnetic field
• Apply a de-phasing pulse
• Measure RF - signal as protons re-phase
– Related to their individual resonance frequency
• Compared to a reference frequency
– Chemical shift

• Need homogenous magnetic fields – use of

shims
• Taken with standard MRI image
(long scan ~30min in total)
 Prostate spectra

Role of Magnetic Resonance Imaging and Magnetic Resonance

Spectroscopic Imaging Before and After Radiotherapy for
Prostate Cancer Antonio C. et al.J Endourol. 2008 April ; 22(4): 789–794
Common spectra components

• Choline – associated with membrane

synthesis
• Creatine – involved with energy
metabolism
• Citrate – product of normal epithelial cell
metabolism in prostate (not seen in
other cells)
• NAA – N-acetylaspartate, 2nd most
common molecule in brain synthesised
in health neurons
 Brain spectra

Applications of magnetic resonance

spectroscopy in radiotherapy
treatment planning,
G S PAYNE, and M O LEACH, The
British Journal of Radiology, 79 (2006),
S16–S26
 MRI Spectroscopy

• Further conform to tumours

– Dose painting

• Possibility of targeting the cell micro-

environment?
 Cell micro-environment
• Hypoxia
– Tumour grows it outgrows blood supply leaving
areas with significantly lower blood supply
– Usually resistant to radiotherapy and
chemotherapy
– Higher dose

• Proliferation
– Cancerous cells uncontrolled and fast division
– Radiosensitivity changes during cell cycle
• more sensitive during division
– Possibly require less dose
 Prostate spectra

Applications of magnetic resonance spectroscopy in radiotherapy

treatment planning,
G S PAYNE, and M O LEACH, The British Journal of Radiology, 79 (2006), S16–S26
 Limitations
• Resolution ~6mm
– Stronger magnetic field
• Scan duration additional 10-15min
– Done as part of MRI scan (anatomical fusion)
• Need flat top couch, lasers etc.
• Respiratory motion issues

• Need proper comparisons to histology – gold

standard
 MRI spectroscopy – trials
• Still a new technique
– Trials needed for histology comparisons
• Need to look for correlation between MRS
signals and local recurrence
• Demonstrate improvement in survival

• Become routine and robust

 Dynamic contrast enhanced
MRI
• Introduction of a contrast agent:
– Paramagnetic – Gadolinium (or manganese)
• Dynamic – so images acquired with time
– Depends on pulse sequence, 30ms to ~1s
• Tumour delineation
• Response to treatment
 Dynamic contrast enhanced
MRI

Cervix tumour
 Tracer kinetic analysis of DCE-
MRI
DCE-MRI data can be analysed with a data
tracer kinetic model, e.g. two-
compartment exchange model (2CXM1) to obtain estimates of
microvascular parameters
Contrast agent Tumour capillary
Ca(t) = concentration
of contrast agent in
artery, arterial input
function (AIF) Vein

vp = vol. of plasma
Fp
space
PS
Ca(t)
vp Fp = plasma flow
PS = permeability-
surface area
Artery

Intracellular space EES

1 Brix, et al. MRM (2004); 52: 420 - 429
 Why use DCE-MRI?
• Improved delineation of tumours

Glioma on T1-w MR image before and after contrast agent

administration
 DCE-MRI to assess
response of breast cancer to
chemotherapy

• Ductal carcinoma
• Subtraction images at 100s post-
injection
• Ktrans maps
• Before and after 2 cycles of FEC
• ROIs drawn in tumour (green),
normal tissue (red) and fat (blue)
• Curves show reduced
enhancement post-treatment
• COMPLETE response at 6 weeks
post-treatment
 DCE-MRI to assess
response of breast cancer to
chemotherapy

• Ductal carcinoma
• Before and after 2 cycles of FEC
• ROIs drawn in tumour (green),
normal tissue (red) and fat (blue)
• No reduction in enhancement
post-treatment
• Tumour size and Ktrans values
largely unchanged
• NO response at 6 weeks post-
treatment
 Dynamic contrast enhanced
MRI
• We’ve seen DCE-MRI is useful for
tumour delineation but real use is for
quantifying tumour behaviour
• Can provide dynamic (temporal)
information about the tumour
• Use to assess response to treatment
 Other uses/considerations of
Magnetic Resonance?
• Full body scanning – bone metastases

• Artefacts
– (not just CT that suffers from artefacts)
MRI - Whole Body Screening
MRI artefacts
 PET
• Expansion of PET into other areas
– Scope in developing the technology - mainly software
– Gating PET
– Use of PET require the same high quality CT images?

• Quantifying uptake and location of

pharmaceuticals

• Cell micro-environments (development of

tracers)
– Hypoxia
– Proliferation
Increased Axial FoV
e.g. 34 rings

Sensitivity ↑78%
 Developments in PET
• Number of Detectors • Image Quality

Siemens/CTI HRRT
Nutt 2002 Mol Imag Biol 2002 4(1) 11 ~2002
 Time of Flight

Karp et al 2005
Wong et al 1983 JNM 24(1) 52-60 IE3-NSS/MI Conf Record
 ToF - Discussion
• Benefits
– Excellent time resolution re. count-rate
performance and randoms rejection
– ~Maintenance of image quality for large
(how large?) patients
• Issues
– Stability
– How many patients really benefit
• Soon all PET systems will be ToF?
 Distribution of 18FDG in Big
Patients
• 77 kg • 128 kg
CT non-ToF ToF
 Application specific scanners
• Why?
– Broadening, b = d  tan 0.25°
– Sensitivity ~ Solid Angle

• Brain
– e.g. Siemen/CTI HRRT, ~2mm resolution
• Breast
– “PEM” Positron Emission Mammography
• Animal
– e.g. HIDAC, ~1mm resolution
 Brain PET
• HRRT (Siemens/CTI)
– High Resolution
Research Tomograph
 Brain PET

• HRRT • GE Advance
 Future Uses of PET-CT
• Oncology
– Further clinical indications
– Alternative tracers, beyond 18FDG
– Combined use of high-quality-CT in PET-CT
– PET-CT for radiotherapy planning
– PET-CT in clinical trials
• Pharmacokinetics (i.e. where the drug itself goes) &
• Pharmacodynamics (i.e. what the drug does)
• Neurology
– Differential diagnosis in dementia
– Identification of epileptic foci
• Cardiology
– Combined rest/stress perfusion with 82Rb (from 82Sr generator)
and CT-angiography on PET-CT
– ? Viability with 18FDG
 Pharmacokinetics
Transaxial slice

Anterior

Anterior Posterior
R L
R L

Posterior

Coronal slice Sagittal slice

•PET/CT is a BIG advantage

LN Aortocaval Lymph node Patient 2-TL 4hr PET

Aortocaval lymph node on
selected PET and CT slices
 Pharmacokinetics
• FDG • 11C-”Drug”
Pharmacodynamic – e.g. with FDG

30

25

20
SUVmax

15

10

0
Baseline Day 8 Day 29
Lesion 1 7.97 6.03 7.47
Lesion 2 9.95 9.20 10.63
Lesion 3 28.16 13.69 14.35
 CT Quality in PET-CT

• Conclusion may very well be completely

different for different clinical question,
e.g. initial staging of NSCLC by PET/CT
 Contrast CT
CT (of PET-CT) 18FDG-PET

External CT Contrast Fused PET-CT

Breath-hold
mAs
 Dose painting
• Higher dose to hypoxic areas, lower/same to
areas of proliferation?
• Shape dose to local PET voxel intensities
• Need additional information – CT + MRI
– (better resolution ~1mm)
• Really need a combination of imaging
modalities
• Truly individualised treatments or standard
tumour models?
• How best to escalate dose to level of
hypoxia?
 Dose painting – conclusion
• Possible to implement – trials are
underway
• Require multi-modality imaging
• Dynamic PET imaging with MRI may be
best current combination
– Fused to planning CT scan
• Just escalate dose or better to redistribute
dose?
 Conclusion
• We have many imaging modalities to call
upon
– Each with pros and cons
• How do we best combine these modalities?
– Benefit to the patient
– Better GTV delineation
• Imaging cell micro-environment
– Truly individualised treatments
– Dose painting
• Experience needed (and trials)