eview of absorbed dose calculation methods...

REVIEW OF ABSORBED DOSE CALCULATION METHODS: IMPLICATIONS FOR FUTURE CLINICAL IMPLEMENTATION

Alex Vergara Gil: [email protected] / Manuel Bardiès: [email protected]

mailto:[email protected]

mailto:[email protected]

CONCEPTS

I. BASIC DOSIMETRY a) ABSORBED DOSE IS DEPOSITED ENERGY IN A MASS ELEMENT!b) CONDITIONS:

1. A RADIATION SOURCE VOLUME SOMEWHERE

2. A TARGET VOLUME SOMEWHERE

3. THE INTENSITY AND CHARACTERISTICS OF THE RADIATION WILL BE CHANGED ON ITS WAY TOWARD THE TARGET VOLUME!

III. EQUATION USED IN SOME SPECIFIC REGION BASED METHODS (2)

a) A0 IS THE INJECTED ACTIVITY

b) EDEP DESCRIBES THE ENERGY RATE ABSORBED IN THE TARGET R PER UNIT DISINTEGRATION

c) M IS THE MASS OF THE TARGET REGION R IN TIME

d) THE INTEGRATION IS PERFORMED USING PHARMACOKINETICS IN THE TARGET REGION R

II. COMMON EQUATION FOR DOSIMETRY IN NUCLEAR MEDICINE (1)

a) Ã IS THE TOTAL NUMBER OF DISINTEGRATIONS (CUMULATED ACTIVITY) IN THE SOURCE H

b) S DESCRIBES THE ENERGY, EMITTED FROM THE SOURCE H, ABSORBED IN THE TARGET K PER MASS UNIT AND

DISINTEGRATION.

CLINICAL DOSIMETRY

• Multiple steps procedure

• Not just calculation

• Codes/software may address ≠ parts

CLINICAL DOSIMETRY

• Absorbed dose: calculated for a purpose

• Disease/Radiopharmaceutical/Isotope specific

• Not a UNIQUE solution

• There may be different codes for different use…

CLINICAL DOSIMETRY

• Academic software– Developped by research groups

– Opensource?

– Availability (±…)

– Research: not for clinical use...

• Vendor software– Meant for the clinics

– Aim for FDA/EMA approval

ABSORBED DOSE CALCULATION

Monte-Carlo

Convolution

Local energy

deposition

Speed

Accu

racy

S FactorsPatient Specific


Monte-Carlo

Convolution

Local energy

deposition

Speed

Accu

racy


days

hours

minutes

minutes

Year 2000


Monte-Carlo

Convolution

Local energy

deposition

Speed

Accu

racy


hours (typically 1-4)

minutes

seconds

seconds

Question: Is Monte Carlo the Holy Grail?

Answer: No

Today, year 2018


Monte-Carlo

Convolution

Local energy

deposition

Speed

Accu

racy


• Accuracy is patient specific, isotope specific and region specific

• Monte Carlo is not applicable in all cases

MEDIRAD

IMPLICATIONS OF MEDICAL LOW DOSE RADIATION EXPOSURE

DELIVERABLE 3.3DOSIMETRY PROTOCOL AND SOFTWARE

LEAD PARTNER:

Workflow Diagrams defining protocol approaches made by:Manuel Bardies, Bernard Guibaud, Marine Brennet, Alex Vergara Gil, Juan Camilo Ocampo Ramos,Erick Mora Ramirez

PANDORA Project

2D DOSIMETRY

• SET OF PLANAR IMAGES (CAN BE WB) IS ACQUIRED AT DIFFERENT TIME POINTS

• REGION BASED QUANTIFICATION

• USE OF TABULAR DATA FOR REFERENCE MODELS IS USED TO CONVERT MEASURED ACTIVITY INTO DOSE

2D DOSIMETRY

Acquisition and processing workflowDetermination of A

Dosimetry workflow:Determination of SIntegration in timeRadiobiology

2D DOSIMETRY

• WORKFLOW : DOSIMETRY

Time Activity Curve Fit(Pharmaco.K Assessment)

Radio-Biological Calculation

Biological Effective Dose

Radio-biologicalcalculation method

Mean Absorbed Dose Rate (ROI1, 2,…., n-1, n)

Net administeredActivity

Time integrated activityper ROI(cumulated activity) 1,

2,…., n-1, n

Time integrated activitycoefficients per ROI(residence time)1, 2,…., n-1, n

Mean Absorbed Dose (ROI1, 2,…., n-1, n)

Organ S-value

Patient organmass (Opt)

Time Absorbed Dose Curve Fit(Pharmaco.K Assessment)

Data Activity per ROI

Absorbed Dose Calculation

Model-based absorbed dose calculation

Adjusted model-based absorbed dose calculation

(if patient organ mass)

Data Activity per ROI

Patient organ mass(ROI1, 2,…., n-1, n) (Opt)

Absorbed Dose (1 value)(ROI1, 2,…., n-1, n)

TimePoint1, 2,…., n-1, n

Absorbed Dose Rate Calculation

• Model-based absorbed dose rate

calculation

• Adjusted model-based absorbed dose

rate calculation

PK assessmentmethod

Radio-biologicalcalculation parameters

PK assessmentmethod

Net administeredActivity

ASIDE OF ABSORBED DOSE CALCULATION

• We need to consider that Absorbed Dose calculation is not isolated process in the workflow

– Is deeply inserted in the whole workflow

– The procedure depends on the techniques used to acquire the images

– The accuracy depends on the techniques used to process the images

– The result of this calculations are not the goal of dosimetric workflow, these are just intermediate step

BEYOND ABSORBED DOSE

• RADIOBIOLOGY CONSIDERATIONS

EUD / TCP

• Prideaux et al. ”Three-Dimensional Radiobiologic Dosimetry: …“. J Nucl Med 2007; 48:1008–1016.

• Wessels et al. “MIRD Pamphlet No. 20: …”, J Nucl Med 2008; 49:1884–1899

• Sgouros et al. “Three-Dimensional Imaging-Based Radiobiological Dosimetry”. Semin Nucl Med 2008; 38:321-334.


Monte-Carlo

Convolution

Local energy

deposition

Speed

Accu

racy


LOCAL ENERGY DEPOSITION

• The degree zero of dosimetry…• However… If activity is known with a

spatial sampling > radiation range...• What is the point in

propagating radiation?• OK for alpha, beta? (microdosimetry)• Not OK for gamma, X. BUT most often a

very minor component of absorbed dose delivered to a given organ...

Some dosimetry software uses a hybrid method of LED for alpha, beta and Monte Carlo for photons using the best of both methods

The energy emitted by the particle is totally absorbed in the point of origin.

S FACTOR CALCULATION

MIRDOSE3

OlindaRefined analytical phantoms

Voxelized phantoms


Voxel

Stylized

Hybrid

1950 1960 1970 1980 1990 2000 2010

ICRU

sphere

1950’s

MIRD/ORNL

1980’s

ICRP/ICRU

2009

Hybrid

Hybrid phantoms are stylized derived from voxelized


Divoli et al. (2009) JNM 50(2):316-323

Using Monte Carlo


Phantoms

Dosimetric

Models

OLINDA/MIRDO

SE3

KERNEL CONVOLUTION

Giap et al. Phys Med Biol. 1995, Mar;40(3):365-81

Monte Carlo

KERNEL CONVOLUTION

Giap et al. Phys Med Biol. 1995, Mar;40(3):365-81

Monte Carlo

3-D Map of Cumulated Activity

Concentration

Absorbed DoseD(r)

KERNEL CONVOLUTION

Monte Carlo

Deposited Energypoint kernel

E(f,t)=A(f,t).k(f)

Targetorgan/voxel mass

KERNEL CONVOLUTION

VOXEL CONVOLUTION

HCC treated with 90Y microspheres

Courtesy: A Dieudonné (VoxelDose)

Pre-calculated voxel S-Factors

MONTE CARLO

ADVANTAGES

Non homogeneous Tissues

FUNTIONAL IMAGE

ANATOMIC IMAGE

INTE

RFA

CE

MC SIMULATION3D Absorbed Dose

Distributions

DVHIsodose Curves

Mean, Max Values

(MCNPx, EGSnrc, GEANT4, GATE, etc)

VOI Analysis

Tables of Absorbed Dose per VOI

MONTE CARLO

VOXEL VS. REGION APPROACHES

Why voxels are not necessarily the best option...

Peter et al. 2000 IEEE transactions on medical imaging, 19(5), pp. 556-64

MULTISCALE DOSIMETRY

Marcatili et al. PMB 2014

3D DOSIMETRY – VOXEL BASED


• THERE WERE NO SIGNIFICANT DIFFERENCES IN THE KIDNEY VOLUMES BETWEEN CYCLES. HOWEVER, THE KIDNEY VOLUMES

THAT WERE MEASURED AT THE FIRST AND THE FOURTH TREATMENTS LAY WITHIN 10% OF EACH OTHER FOR ONLY 12 OF

24 PATIENTS (50%). ONE PATIENT HAD AN INCREASE IN SIZE OF MORE THAN 20% IN THE RIGHT SIDE KIDNEY AND

ANOTHER PATIENT HAD A SIMILAR INCREASE ON THE LEFT SIDE. ONE PATIENT HAD A LEFT-SIDED DECREASE BY MORE THAN

20%.


Real problematic with registration based approaches

T0: Diagnostic CT, full stomach, liverand spleen displaced

T1: Low Dose CT, empty stomach, liver and spleen displaced

The lesion is also displaced and the shape has changed!!

Image courtesy of: Institute of Cancer of Montpellier

3D DOSIMETRY

I. MAIN ISSUE WITH 3D DOSIMETRY – SEGMENTATION

a) DEPENDENT OF THE TECHNICIAN, USUALLY NEEDS CLINICIAN VALIDATION

b) TAKES LOADS OF TIME, ACTUALLY MORE THAN MC SIMULATION ITSELF!c) USED EVERYWHERE, TO DEFINE THE MEDIAS FOR SIMULATION, TO DEFINE THE MASS AND ACTIVITY, TO

DEFINE THE REGIONS FOR PK INTEGRATION IN TIME

MULTISCALE DOSIMETRY

Marcatili et al. PMB 2014

CLINICAL DOSIMETRY


– Opensource?





CONVOLUTION

RMDP (M Guy, RMH) NukDos (M Laßmann, UKW)

MONTE CARLO

Kolbert KS, Sgouros G, Scott AM, et al. J Nucl Med. 1997;38:301–308.

• Osem Reconstruction (OSEM)

• Image Processin (MIAU)

• Image Corregistration

• Dose Claculation by Monte

Carlo techniques and the

kernel methods.

• Curve fitting at voxel level.

• Radiobiology analysis of data

3D-ID. Implementation and evaluation of patient-specific three-dimensional internal dosimetry. (Memorial Sloan-Kettering Cancer Center, NY, USA)

(3D-ID / 3D-RD)

MONTE CARLO

131I

d0, d1, d3, ...

MCNPX

S Chiavassa et al. (2006) PMB 51:601-616

MONTE CARLO

S Chiavassa et al. (2006) PMB 51:601-616

Application : LipioCis™

• 194 x 140 x 90 voxels

• (2.21 x 2.21 x 4.42 mm3)

• Organ : 45 min (σ<2%)

• Voxel : 3.8 d (σ<10%)

MONTE CARLO

CANCER BIOTHERAPY & RADIOPHARMACEUTICALS Volume 20, Number 1, 2005

The LundADose Method for Planar Image Activity Quantification and Absorbed-Dose assessment in RNT (Lund University. Sweden)

DOSIMG

MONTE CARLO

CANCER BIOTHERAPY & RADIOPHARMACEUTICALS Volume 30, Number 1, 2015

MONTE CARLO

Courtesy: E Spezi (Velindre, Cardiff)Marcatili et al. Phys Med Biol 2013 58 2491-2508

CLINICAL DOSIMETRY


– Opensource?





EXAMPLE OF COMMERCIAL WORKSTATIONS

ReportRT-Dose

Comparison

99Tcm-MAAdosimetry 90Y-microspheresdosimetry

Invivocontrol

TherapyresponseRECIST1.1,PERCIST1.0

Post-treatmentexams

Follow-up

Pre-treatmentexams

Review,segmentation,quantification

Diagnosis

Multi-modalimageregistration

Post-implantationdosecalculation

90Y-microspheresPET/CTexam

TreatmentPlanning

Segmentationand/orstructureimport

Pre-implantationdosecalculation

99Tcm-MAASPECT/CTexam

RT-Struct

Processing workflow


• Vendor Software (DosiSoft)

• Treatment planning system for SIRT & now systemic therapy dosimetry

• CE marking! Clinical solution

• Absorbed dose calculation: LED & Convolution

• Dose Volume Histograms


HERMES Dosimetry Software Current overview and future directions

April 2015

[email protected] HERMES Dosimetry Software Current overview and future directions

April 2015

[email protected]

Important player in Nuclear Medicine“Nuclear Diagnostics”Multimodality workstationManufacturer independent…Research Tool: FDA approval pendant



April 2015

[email protected]

Hybrid ViewerTM Dosimetry [MIRD Calculation]

Can be used with the following combinations of data - Multiple Planar - Multiple Planar + one SPECT-CT - Multiple SPECT-CT or PET-CT

MIRD Phantom

Voxel Based

SPECT Recon

Introduction

SIRT Microspheres



April 2015

[email protected]

• Historically 3D voxel-based dosimetry is time-consuming

• HERMES has developed Hybrid 3Dose-package, which combines the following dosimetry steps in a clinically valid time:

1. Reconstruction 2. Registration 3. Curve-fitting 4. MC-based dose calculation 5. Semiautomatic ROI drawing of organs from CT 6. Automatic lesion detection 7. Reporting

Hybrid 3Dose – Monte Carlo

Voxel Based

MIRD Phantom

SPECT Recon

Introduction

SIRT Microspheres


STRATOS

• Vendor Software (Philips)

• From clinical images to absorbed dose– Essentially 3D!

• Computation: kernel convolution (no mass adjustment)– Dose Volume Histograms

• Research Tool: NO FDA/EMA/CE approval


DOSIMETRIX

• Vendor Software (GE)

• From clinical images to Residence time– Essentially 3D!

• NO Absorbed dose calculation!– Uses MIRD S Factors (Future?)

• Clinical Tool: FDA/EMA/CE approval

COMMERCIAL WORKSTATIONS AVAILABLE AT CRCT

COMMERCIAL WORKSTATIONS AVAILABLE AT CRCT

PDOSE STRATOS

STRATOS is part of the IMALYTICS

Research workstation (Imalytics3.2, Rev 6289(64)) by Phillips,and operates on Windows. Itallows the user to perform 3Ddosimetry from multiple SPECT/CTscans. Registration (MN-1CT) andsegmentation can be done in theMN & CT matrices. It can generateTAC’s and performs fitting byusing the trapezoid method. Itperforms voxel-based dosimetry(convolution). It can be used for18F, 68Ga, 124I, 131I, 111In, 177Lu,99mTc, 90Y, 188Re, 166Ho,153Sm.

Hybrid Viewer DosimetryModule™ (HVD), version 1.0 byHERMES works on Windows. It hasFDA approval. It can be used withat least 3 SPECT/CT scans or 3whole body scans (WB’s) and oneSPECT/CT or 3 WB’s.Reconstruction can be done aswell as registration, segmentation(MN&CT). It can generate TAC’sand performs mono-exponential(3 scans) and bi-exponential (4scans minimum) fittings.Residence time results areexported to OLINDA/EXM V2.0. Itcan be used for 11C, 18F, 67Ga, 68Ga,123I, 131I, 111In, 177Lu, 13N, 15O, 82Rb,99mTc, 201Tl, 90Y, 188Re, 166Ho, 81Kr.

PLANET® Onco Dose (PDOSE) ,Edition 3, version 3.0 was createdby Dosisoft, operating on Linux(7.3.1611, CentOS7 -64bits).PDOSE for Selective InternalRadiotherapy (SIRT 90Y) has FDAapproval. PDOSE can also be usedfor Nuclear Medicine systemictherapy (177Lu). It allows the userto perform full 3D dosimetry fromreconstructed images.Registration of multiple SPECT/CTscans segmentation can be donein the MN & CT matrices. It cangenerate TAC’s and it has multiplefitting options. Now performorgan-based and voxel-baseddosimetry.

COMMERCIAL WORKSTATIONS AVAILABLE AT CRCTActivity estimation

Activity estimation for OSEM (6i, 10ss) + AC + RR + SC + Non GPF

Day Time

Activity (MBq) % Relative difference in

activity

FittingMono-ExponentialResidence time (h)

% Relative difference in

Residence timeSoftware

Theoric Estimation

27/04/16 19:28 529.80 550.62 -3,9

241.93 4.439 HVDM

28/04/16 17:56 480.53 499.73 -4,0

29/04/16 18:01 432.78 463.17 -7,0

03/05/16 19:15 283.66 297.51 -4,9

04/05/16 17:40 257.33 267.11 -3,8

27/04/16 19:28 529.80 546.72 3,2

222.00 -3.543 PLANET

28/04/16 17:56 480.53 480.75 0,04

29/04/16 18:01 432.78 432.86 0,01

03/05/16 19:15 283.66 283.18 -0,17

04/05/16 17:40 257.33 251.72 -2,2

27/04/16 19:28 529.80 560.00 5.7

114.00 -50.52

STRATOS*(fitting

trapezoidal method)

28/04/16 17:56 480.53 390.00 -18.8

29/04/16 18:01 432.78 350.00 -19.1

03/05/16 19:15 283.66 110.00 -61.2

04/05/16 17:40 257.33 100.00 -61.1

FINAL REMARKS

• No unique solution for dosimetry.– Different modalities = different approaches

• No available solution yet for mass variation with time, for correction of registration process and for accurate automatic segmentation.

MERCI DE VOTRE ATTENTION

THANKS FOR YOUR ATTENTION

Centre de Recherches en Cancérologie de Toulouse

www.crct-inserm.fr

NUCLEAR MEDICINE QC PLUGINS

NUCLEAR MEDICINE E-LEARNING

http://www-

naweb.iaea.org/elearning/NMDI/Quality_Assurance_for_SPECT_Systems/story.html

16 tutorial videos

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