quantitative imaging and dose calculation comparison...

Quantitative Imaging and Dose Calculation Comparison Exercises in

the MRTDosimetry Project

J Tran-Gia1, M Lassmann1, J Tipping2, N Calvert2

1Department of Nuclear Medicine, University of Würzburg2Nuclear Medicine Group, The Christie NHS Foundation Trust, Manchester

Aims of Comparison Exercises

2

1. Need for standardization of quantitative imaging

– Problem: Numerous imaging modalities & systems.No standardization of activity determination.

– Plan: Comparison exercise with different SPECT/CT systemsBUT standardized activities & reconstructions.

– Aim: Protocol for commissioning and QI.

2. Lack of validation between dosimetry software tools

– Problem: Numerous tools available for dose calculation.No validation across different tools.

– Plan: Calculate doses with available dosimetry tools basedon simulated post-therapy dosimetry dataset.

– Aim: Protocol for commissioning dosimetry platforms.+ many in-house approaches

Participating Systems

3

AOSP GE Discovery 690 2016 3/8"

ASMN Siemens Symbia T2 2009 3/8"

Christie 1 GE Discovery 670 2015 3/8"

Christie 2 GE Infinia Hawkeye4 2006 3/8"

LUND GE Discovery 670 2012 5/8"NPL Mediso AnyScan SCP 2017 3/8"

OUHT 1 GE Discovery 670 2011 3/8"OUHT 2 GE Infinia Hawkeye4 2008 3/8"

RSCH 1 GE Optima NM/CT 640 2014 3/8"THG (PGNI) GE Optima NM/CT 640 2015 3/8"

UKW 1 Siemens Symbia T2 2006 5/8"

UKW 2 Siemens Symbia Intevo 2016 3/8"

SPECT/CT Hardware available at Participating Sites:

• 5 Countries.• SPECT/CT systems of 3 large vendors.• 2 different detector crystal thicknesses.

Outline

Quantitative Imaging Comparison Exercise (UKW)

1. Sensitivity Determination (Jaszczak Cylinder)

2. Partial Volume Assessment (6-sphere Phantom)

3. Quantitative Imaging Exercise (3D-printed 2-organ Phantom)

4. Validation of Radioactive Test Sources (Ba-133 Surrogate vs. Liquid I-131)

Dose Comparison Exercise (The Christie)

1. Extend Printed Phantom (4-Organ 3D-printed phantom)

2. Generation of Ground Truth TAC & Dose (PK Model & MC Simulation)

3. Measurement of TAC (Experimental & MC Simulation)

4. Dose Calculation & Comparison (Commercial & in-house)

4

Outline











5

Part 1 & 2

SensitivityPartial Volume

Part 3

3D-printed ICRP2-organ phantom

Part 4

Sealed Ba-133vs. liquid I-131

Ba-133 Liquid I-131

1.1 Sensitivity Determination

Goal

6

Counts in

each voxel

Activity per voxel

→ Activity distribution

Reconstruction

Conversion according to

sensitivity (cps/MBq[1])

Counts → Activity

?

[1] Counts-per-second-per-MBq


Calibration protocol(produced within the MRTDosimetry project)

7

Approach• Fill large phantom (to reduce partial volume effects) with

traceable amount of activity.

• SPECT/CT imaging (TACQ) + clinical reconstruction.

• Calculate conversion factor:

• Unit: counts-per-s-per-MBq (cps)


8

Aphantom

Total live time

Total counts

Decay-corrected activity

FilledPhantom

SPECTImaging

ctotal


Protocol:

Suggestions on Carrier Solution(MRTDosimetry: Only Lu-177 and I-131)

9

Suggestions onPhantom Filling

www.biodex.com

> 20 cm

> 18 cm< 10 L

Suggestions on Phantom Selection

Protocol: Suggestions on SPECT/CT Acquisition• Positioning in center of rotation.

• Acquisition parameters as in clinical protocol

(e.g. 2×60 projections, 30s-per-projection, non-circular orbit).

• Low-dose CT for attenuation correction.


10

SPECT/CT Positioning

Protocol: Suggestions onSPECT/CT Reconstruction

• Projection-wise decay correction.

• Scatter (e.g. triple-energy-window) & attenuation correction (e.g. CT-based) as in clinical protocol.

• Filtering (e.g. Gaussian post-filtering) & resolution recovery as in clinical protocol.

• Iterate until number ofcounts has convergedas function of updates(iterations × subsets).


11

SPECT/CTReconstruction


12

Example from UKW (Lu-177)

Lu-177 SPECT/CT FusionFlash3D, 6i6s0mm

SPECT

Protocol: VOI Analysis• Define cylinder ROI in central transaxial slice.

• 130% of phantom radius.

• 120% of phantom length.

Calculate conversion factor


13

VOI

Phantom


Goal

14

Counts per

Voxel

Activity per voxel

→ Activity distribution

Reconstruction

Conversion according to

sensitivity (cps/MBq)

Counts → Activity

?!

Outline







1. Your Choice ☺

15

Part 1 & 2


Part 3


Part 4


Ba-133 Liquid I-131

1.2 Partial Volume Assessment

16

Image Formation:

Convolution of object and point spread function of imaging system.

(„How the imaging system see the object”).

Source: Wikipedia Simulation

PSF(Gaussian)

Partial Volume Effect(„Spill-Out“ vs. „Spill-In“)

FWHMSPECT: 1-2 cm

All spheres should ideally have homogeneous SPECT signal.Goal of this section: Assess the partial volume!

Approach• Fill sphere phantom with known geometry (known radii) with

traceable amount of activity (Asphere,i).

• SPECT/CT imaging (TACQ) + clinical reconstruction.

• Draw sphere VOIs based on nominal diameters and CT.

• Obtain ratio of spilled out counts:


17

SpherePhantom𝑅𝐶(𝑖) =

𝑐𝑡𝑜𝑡𝑎𝑙𝐴𝑠𝑝ℎ𝑒𝑟𝑒,𝑖 ∙ 𝑇𝐴𝐶𝑄 ∙ 𝐶𝐹

SPECT/CTFusion & VOIs

SPECT

ctotal

From 1.1

Optional in calibration protocol (Appendix)

MRTDosimetry comparison exercise• IEC NEMA Phantom

• 6 sphere inserts (diameters: 10–37 mm, volumes: 0.5–26.5 ml)


18

http://www.biodex.com


Phantom Filling Procedure(This procedure assumes that the spherevolumes Vsphere i were pre-measured)

• Prepare Stock solution (500 ml container).

• Ensure spheres are empty.

• Fill spheres until liquid “rises up along capillary”.

• Sphere activities:

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𝑐𝑠𝑡𝑜𝑐𝑘 𝑠𝑜𝑙𝑢𝑡𝑖𝑜𝑛 =𝐴𝑠𝑦𝑟𝑖𝑛𝑔𝑒,𝑓𝑢𝑙𝑙 − 𝐴𝑠𝑦𝑟𝑖𝑛𝑔𝑒,𝑒𝑚𝑝𝑡𝑦

𝑤𝑐𝑜𝑛𝑡𝑎𝑖𝑛𝑒𝑟,𝑓𝑢𝑙𝑙 − 𝑤𝑐𝑜𝑛𝑡𝑎𝑖𝑛𝑒𝑟,𝑒𝑚𝑝𝑡𝑦

𝐴𝑠𝑝ℎ𝑒𝑟𝑒 𝑖 = 𝑐𝑠𝑡𝑜𝑐𝑘 𝑠𝑜𝑙𝑢𝑡𝑖𝑜𝑛 ∗ 𝑉𝑠𝑝ℎ𝑒𝑟𝑒 𝑖

500 ml Container

CarrierSolution

Activity


20

Acquisition & Reconstruction as for sensitivity.


21

Example from UKW (Lu-177)Lu-177 SPECT/CT Fusion

Flash3D, 6i6s0mm

SPECT

Recovery Curve Fitting• Ratio of spilled out counts:

• Plot RC(i) against sphere volume Vi

• Obtain volume-dependent recovery coefficient curve by fitting (α, β, γ: coefficients for fit, V: sphere volume):


22

𝑅𝐶(𝑉) =𝛼

1 + Τ𝛾 𝑉 𝛽

RC(V) curve

𝑅𝐶(𝑖) =𝑐𝑡𝑜𝑡𝑎𝑙

𝐴𝑠𝑝ℎ𝑒𝑟𝑒,𝑖 ∙ 𝑇𝐴𝐶𝑄 ∙ 𝐶𝐹

SPECT/CTFusion & VOIs

SPECT

ctotal

Correct partial volume by volume-based recovery coefficient(strictly: correction restricted to sphere geometry).

0.21

0.530.73

0.78

0.810.87

Outline







1. Your Choice ☺

23

Part 1 & 2


Part 3


Part 4


Ba-133 Liquid I-131

→ Validate QI in quasi-realistic, anthropomorphic phantom

1.3 Quantitative Imaging Exercise

24

3D Printing Template:

2 Organs (Kidney & Spleen)

of ICRP 110[1] Voxel Phantom

• Average male/female.

• Segmented & modified CT of individual.

• Voxel size (1.8 x 1.8 x 4.8 mm3) places limit on resolution of organs.

• Accepted as dosimetry standard.

[1] ICRP Publication 110. Ann ICRP 39(2), 2009.


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Phantom Design

Voxels

Convert voxelsto surface

Smoothensurface

Extrude walls, addfilling & supports, cut

Cortex

Medulla


26

Phantom Fabrication

Print Seal

FDM 3D-Printing (Ultimaker 3)

Printed parts (Medulla & Cortex)

Completed phantom


27

Phantom Fabrication

Spleen

Bottom baseplate

Final design Final printed phantom

Support rods

Kidney

Top baseplate

Jaszczak phantom


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• Designed for the MRTDosimetry project as QI phantom.

• Fits a standard Jaszczak phantom.

• One phantom set will be sent to each participating partner site.

“Bulk production” SPECT/CT quality control

Phantom Fabrication


29

Lab Balance

Dose CalibratorClamp Stand

Container

2 Stock Solutions:

• High Activity Concentration(Kidney Medulla)

• Low Activity Concentration(Spleen & Kidney Cortex)

Phantom Filling: Setup at UKW

High Low

High


30

Phantom Filling: Spreadsheet

To be filled out by participant / Automated uncertainty estimation


31

Filling & Mounting: Step-by-Step Instructions

Filling Instructions

Mounting Instructions


32

Acquisition & Reconstruction as for sensitivity & partial volume.

Phantom-specificorgan-positioning!


33

Lu-177 Measurement at UKW:• Flash3D (Siemens’s OSEM).• Attenuation correction.• Scatter correction.• Resolution recovery.• 4 iterations, 8 subsets.• No post-filtering.

SPECT/CTFusion

SPECT

Outline







1. Your Choice ☺

34

Part 1 & 2


Part 3


Part 4


Ba-133 Liquid I-131

→ Test Ba-133 as surrogate for liquid I-131

35

1.4 Validation of Radioactive Test Sources

Quality control often based on liquid sources.→ Disadvantages regarding time effort & radiation protection.

Idea:Replace liquid I-131 sources by sealed Ba-133 sources.

0.21

0.530.73

0.78

0.810.87

• Design of 4 Ba-133 sealed sources.

• Production of 4 identical containersto be filled with liquid I-131.

• Validate sealed Ba-133 against liquid I-131 sources.

36

Ba-133

LiquidI-131

3D printedcontainers

Concentration(kBq/g)

Activity(MBq)

Diameter (mm)

Length(mm)

Volume (cm^3)

200 0.34 7.5 38.0 1.7

200 1.34 15.0 38.0 6.7

200 5.38 30.0 38.0 26.9

200 21.48 60.0 38.0 107.4


Dimensions & Activities

CAD Models.

37


d = 21.6 cm7.5mm/40mm

15mm/50mm

60mm/95mm

30mm/60mm

Jaszczak PhantomSolid Sources

Partial Volume

Estimation of partial volume effects(resolution high energy collimator: 20 mm)

Baseplate produced by Christie

Attachment holesJaszczak cylinder


38

• Production of sealed Ba-133 sources by CMI, Czech Republic and CEA, France.

• Production of hollow containers for liquid I-131 comparison.

Ba-133 source production at CEA. Hollow 60-mm containerattached to baseplate.

Fillinghole


39

Attach Ba-133 sources.Close Phantom.

Attach base plate (3 screws).Attach attachment rods (4 circles).Fill with water.

Positioning on patient bed.

Filling, Mounting, Acquisition & Reconstruction: Step-by-Step Instructions

40


Ba-133 Measurement at UKW:• Flash3D (Siemens’s OSEM).• Attenuation correction.• Scatter correction.• Resolution recovery.• 4 iterations, 8 subsets.• No post-filtering.

SPECT/CT Fusion4i8s0mm

SPECT

41

Outcomes / Deliverables

QI Comparison Exercise:

• Protocol for commissioning and QC of SPECT/CT imaging systems.

• Multi-center assessment of quantitative accuracy of different SPECT/CT systems.

• Validation of Ba-133 as surrogate for liquid I-131.

Aims of Comparison Exercises

42

1. Need for standardization of quantitative imaging

– Problem: Numerous imaging modalities & systems.No standardization of activity determination.

– Plan: Comparison exercise with different SPECT/CT systemsBUT standardized activities & reconstructions.

– Aim: Protocol for commissioning and QI.

2. Lack of validation between dosimetry software tools

– Problem: Numerous tools available for dose calculation.No validation across different tools.

– Plan: Calculate doses with available dosimetry tools basedon simulated post-therapy dosimetry dataset.

– Aim: Protocol for commissioning dosimetry platforms.+ many in-house approaches

Outline











43

Part 1 & 2

4-organ phantomGround truth TAC

Part 3

Serial SPECT Imaging

Part 4

Dose Calculations

x S

Outline











44

Part 1 & 2


Part 3


Part 4

Dose Calculations

x S

2.1 Extended 3D Printed Phantom

• Current phantom is useful for QI exercise.

• Not fully representative for Dose Calculations.

Spleen

Bottom baseplate

Support rods

Top baseplate

Jaszczak phantom

45


• 3D Printed phantom extended to include 2 kidneys (each with separate Cortex & Medulla), Spleen, Liver, and Tumour.

• Phantom based on ICRP110 models.

Spleen

Left Kidney

Liver

Tumour

Right Kidney

Kidney

46

Bespokeellipticalphantom


• Imaged in large elliptical phantom.

47


• Preliminary imaging undertaken to help with develop design of printed phantoms.

48

Outline











49

Part 1 & 2


Part 3


Part 4

Dose Calculations

x S

2.2 Ground Truth TAC

• Organ Time Activity Curves:– TAC is required before designing experiments & calculating

ground truth dose.– Mimic Lu-177 Dotatate Therapy.

50

Time (h)

Up

take

Liver

Spleen

2.2 Ground Truth TAC

• Organ Time Activity Curves:– Implemented compartmental Pharmacokinetic model using published data [2], altering the

volumes to match printed phantom– Cortex & Medulla to have 3:1 activity concentration ratio [3].– Initial injected activity: 7.4 GBq equivalent.

[2] Brolin, et al. Phys. Med. Biol. 60 (2015) 6131-6149[3] MIRD Pamphlet 20 JNM 49(11) 2008 1884-1899

51

2.2 S-Factor Computation

• Simulated in Geant4 & Gate to calculate S-Factors for the phantom, required for dosimetry.

Source

Liver LK Cortex LK Medulla RK Cortex RK Medulla Spleen Tumour

S (m

Gy/

MB

q.h

r)

Liver 6.57E-02 3.63E-04 2.96E-04 1.08E-03 8.07E-04 2.93E-04 3.27E-03

LKCortex 3.64E-04 9.10E-01 1.80E-02 4.21E-04 3.76E-04 1.76E-03 2.85E-04

LK Medulla 2.96E-04 1.79E-02 1.94E+00 4.13E-04 3.87E-04 9.87E-04 2.27E-04

RK Cortex 1.08E-03 4.22E-04 4.18E-04 1.09E+00 2.35E-02 1.85E-04 7.91E-04

RK Medull 6.51E-04 3.08E-04 3.17E-04 1.89E-02 1.87E+00 1.30E-04 5.20E-04

Spleen 2.93E-04 1.75E-03 9.81E-04 1.82E-04 1.59E-04 6.71E-01 2.20E-04

Tumour 3.28E-03 2.91E-04 2.30E-04 7.87E-04 6.48E-04 2.24E-04 5.21E+00

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Outline











53

Part 1 & 2


Part 3


Part 4

Dose Calculations

x S

2.3 Post-Therapy Lu-177 SPECT Imaging

• Imaging time point picking:– Different centres have different guidelines

• Site A typically image PRRT patients at 4 time points: 1 h, 24 h, 72 h, 144 h.• Site B at 5 time points: 1 h, 4 h, 24 h, 40 h, 70 h.

– We will image at time points 1 h, 4 h, 24 h, 40 h, 72 h, 144 h allowing us to generate number of datasets of 4, 5, or 6 points.

– Filling & scanning follow SOP defined in QI comparison exercise.

54

2.3 Simulated Measurements

• Lund: simulating SPECT with SIMIND and CT with a stoichiometric calibration method

• INSERM: simulating SPECT with GATE• SCK·CEN: simulating CT with GATE

STLstovoxels

voxelstoproj.

55

2.3 Generating device agnostic images

• Experimental data taken on GE Discovery 670.• Simulated data may be in non-DICOM format.• SCK·CEN have developed tool to convert simulated images

to DICOM with correct header information to be reconstructed on clinical workstations.

56

Outline











57

Part 1 & 2


Part 3


Part 4

Dose Calculations

x S

2.4 Dosimetry systems available

RAYDOSE

LUNDADOSE

VoxelMed

MIDAS

Commercial In House

58

2.4 Dosimetry systems available

Planar Planar + SPECT MULTI-SPECT

Voxelmed

Raydose

Hermes Hybrid Dosimetry™



LundADose LundADose LundADose

GE GE GE

THG THG

NUKDOS NUKDOS

MIDAS MIDAS MIDAS

QDose QDose

DoseFX

Planet® Dose

MIRADA Simplicit90YTM

59

Organ Voxel

Voxelmed Voxelmed

Raydose



LundADose LundADose

GE

THG THG

NUKDOS NUKDOS

MIDAS MIDAS

QDose QDose

DoseFX

Planet® Dose

MIRADA Simplicit90YTM

2.4 Patient Dose Comparison

ASMN, CASE 1, Lu-177 DOTATATE Therapy

SPECT onlySPECT/CT Fusion, 24 h post injection

60


ASMN, CASE 2, Lu-177 DOTATATE Therapy

SPECT onlySPECT/CT Fusion, 24 h post injection

61


0.00

0.50

1.00

1.50

2.00

Liver

0.00

0.50

1.00

1.50

2.00

Total Kidneys

0.00

0.50

1.00

1.50

Spleen

0.00

0.50

1.00

1.50

2.00

2.50

Liver

0.00

0.50

1.00

1.50

2.00

Total Kidneys

0.00

1.00

2.00

3.00

Spleen

Patient 1

Patient 2

Dose(Gy)

Dose(Gy)

Dose(Gy)

Dose(Gy)

Dose(Gy)

Dose(Gy)

Organ-based | Voxel-based→ Statistical analysis challenging (only few statistically independent data points, e.g. 8 data points from 1 site).

WP 4.1.1 of MRTDosimetry

62

2.4 Data collection

• Need to ensure data is collected in same format for easy comparison.• Developed data recording spreadsheet (based on IAEA RaBiT), that

doubles as a checklist to ensure dose calculations have been performed correctly.

[4] IAEA Radiotracer Biodistribution Template (RaBiT) , 2016 63

2.4 Data collection

• Important data to collect include TAC fits, etc, but more importantly the uncertainties associated with these.

• Uncertainties on fit parameters will be used (where possible) to estimate uncertainties on calculated dose values.

64

2.4 Data collection

• Important data to collect include TAC fits, etc, but more importantly the uncertainties associated with these.

• Uncertainties on fit parameters will be used (where possible) to estimate uncertainties on calculated dose values.

65

Data comparison

• Dose calculations – whole organ & voxel-based - compared to ideal and variability across different software.

• Effect of using different time points & different number of time points for the TAC.

• Uncertainties – whether they can be calculated & their value.

0

0.2

0.4

0.6

0.8

1

0 5 10 15Frac

tio

nal

Vo

lum

e

Dose (Gy)

Dose Volume Histogram

Whole organ dose

Voxel-level dosimetry

66

67

Outcomes / Deliverables

QI Comparison Exercise:• Protocol for commissioning and QC of SPECT/CT imaging

systems.• Multi-center assessment of quantitative accuracy of

different SPECT/CT systems.• Validation of Ba-133 as surrogate for liquid I-131.

Dose Comparison Exercise:• Protocol for commissioning dosimetry platforms &

determining overall uncertainty in the absorbed dose quantification process.

• First ground-truth training set for validation of different dosimetry software.

Thank you very muchfor your kind attention!

http://mrtdosimetry-empir.eu/

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