IMAGE-BASED PATIENT-SPECIFIC DOSIMETRY FOR RADIONUCLIDE … · 2015. 3. 18. · Vienna, Austria. Medical Radiation Physics, Clinical Sciences Lund, Lund University BASIC DOSIMETRY

Medical Radiation Physics, Clinical Sciences Lund, Lund University

Michael Ljungberg, PhD, Katarina Sjögreen-Gleisner, PhD

IMAGE-BASED PATIENT-SPECIFIC DOSIMETRY FOR RADIONUCLIDE THERAPY

International Symposium on Standards, Applications and Quality Assurance in Medical Radiation Dosimetry

9-12 November 2010 Vienna, Austria


BASIC DOSIMETRY

Absorbed dose is mean imparted energy in a mass element!Conditions:

A radiation source volume somewhereA target volume somewhereThe intensity and characteristics of the radiation will be changed on its way toward the target volume!

Common equation for dosimetry in Nuclear Medicine

A is the total number of disintegrations (cumulated activity)S describes the energy, emitted from the source volume, absorbed in the target volume per mass unit and disintegration.

D = A S%~


THE ”MIRD” EQUATION

{D A S A A n E mSS

φ= ⋅ = ⋅Δ ⋅Φ = ⋅ ⋅ ⋅% % %

14243

( ) ( ) ( )k hr r r r

r r i T S i T Sih i ihi iT T

n Em

Dm

A Aφ φ

← = ⋅ = ⋅← ←

Δ∑ ∑% %

i i ii i

n EΔ = Δ =∑ ∑n is the number of particles emitted per transitionE is the mean energy per particle

S denotes the sourceT denotes the target

( )( )

Sr r 1

r r 0 ; T Snp T

np T S

φ

φ

← =

← = ≠

( )T S0 r r 1iφ≤ ← ≤Photons

Electrons

Mean energy per disintegration Absorbed Fraction


APPLICATIONS OF DOSIMETRY IN NUCLEAR MEDICINE

Dosimetry for Diagnostic Nuclear MedicineEstimate risk for cancerogenic effects and hereditary changesLow activities / gamma-radiationIndividuals is not in focusPopulationsSpecific for the study but not for the individual patient

Dosimetry for therapy with radionuclidesPrimary aim is to treat a disease with radiationHigh activities / charged particlesThe individual is in focusStudy specific as well as patient specific


DOSIMETRY FOR TREATMENT

Activity (A)Measurement with a ’diagnostic tracer amount ’ for kinetic and dosimetry calculationsPreferably made with a scintillations camera or SPECT/PETUse Gy/MBq to predict activity needed to delived an prescribed absorbed dose to the target

Geometry (S)The more accurate the geometry is - the better.Patient-specific geometry from a CT studySometimes difficult to segment target volumes in 3D

General Goal: To determine absorbed dose for individuals


WHY IS RADIONUCLIDE DOSIMETRY DIFFICULT?

External TherapyWell-defined source and intensityTurn-on and offEnergy usually evenly distributed within a volume elementHigh dose-rate

Radionuclide therapyInjection of the sourceCannot turn the source on and off!Need to measure the activity distribution in time and spaceImaging systems have limitations (spatial resolution, noise,attenuation ..)Localization in the tissues and cells generally heterogeneous Biokinetic may vary with patientsLow dose-rate


THE DIFFICULTIES IN ACTIVITY MEASUREMENTS

A. No patient motion and perfect camera resolutionB. Patient respiration and heart beatingC. Normal system resolution and patient movementsD. Photon attenuationE. Photon attenuation and scatterF. Realistic noise level

A B C D E F

Monte Carlo simulated images


2D DOSIMETRY – PRINCIPLES

Dosimetry based on tools developed for diagnostic dosimetry

Activity from Planar WB measurements (Geometrical-Mean)

S-values calculated from analytical phantoms

Assumes homogenous activity i organ

Calculate mean absorbed dose in organs

Correction for differences in organ masses relative to reference phantom!

A S


AUC

Intensity

[cou

nts]

Time [h]

BIOKINETICS TO OBTAIN CUMULATED ACTIVITY


DEVELOPMENT OF MORE REALISTIC PHANTOMS

May lead to more ’patient specific’ dosimetry

Example: The NCAT phantom by P Segars, Duke University


WHY IMAGE‐BASED 3D DOSIMETRY

Dosimetry based on two-dimensional (2D) whole-body imaging has known limitations.Contribution from overlapping structuresAttenuation correction is 2DScatter correctionSource thickness correctionBackground/overlap correction

3D images provides information of the absorbed dose on a voxel levelHeterogenityCorrections more accuratePatient-specific anatomySPECT/CT on different time points – biokinetics on voxel level

Hybrid SPECT/WB method common compromise!One Quantitative SPECT measurement to nomalise a kinetic curve obtained from multiple WB measurements


3D DOSIMETRY

Multiple registered SPECT/CT or PET/CT studies

Correction forPhoton attenuationScattered radiationCollimator resolutionSeptal penetrationPartial-Volume Effect

3D dose calculation fromDose kernelsMonte Carlo method

Evaluated asDose/volume histogramsRelate to biological effect

Function Imaging SPECT/PET

Function Imaging SPECT/PET

Image Registration

Image Registration Anatomical Imaging CT

Anatomical Imaging CT

Correction for Attenuation and Scatter Collimator Response Septal Penetration

Partial-Volume Effects



Dose Calculation by Dose Kernels Monte Carlo


SegmentationDV Histogram


Obtainbiokinetics

Obtainbiokinetics

Image Reconstruction



3D DOSIMETRY

Modern SPECT/CT (PET/CT) systems makes life easier

Correction forPhoton attenuationScattered radiationCollimator resolutionSeptal penetrationPartial-Volume Effect


Evaluated asDose/volume histogramRelate to biological effect









Obtainbiokinetics

Obtainbiokinetics



Hybrid SPECT/CT

Hybrid SPECT/CT


3D DOSIMETRY

Today Quantification is made by iterative methods

Include correction forPhoton attenuationScattered radiationCollimator resolutionSeptal penetrationPartial-Volume Effect


Evaluated asDose/volume histogramRelate to biological effect

Iterative Methods preferrable

since they allow for correction of

Attenuation and Scatter Collimator Response Septal Penetration

Backscatter




Backscatter





Obtainbiokinetics

Obtainbiokinetics

Hybrid SPECT/CT

Hybrid SPECT/CT


NewImage

Estimate

Forward Projection

EstimatedProjections

Comparing step

Errorprojection

Backproject Error

Update step

MeasuredProjections

Initial Image Estimate

More angles?

Image space Projection space

PRINCIPLES OF THE ML-EM ALGORITHM

yes

More Iterations

Exit

yesRatio


ABSORBED DOSE CALCULATIONS FROM SPECT/PET IMAGES

Dose Calculation

Absorbed Dose RateActivity

Density

( ) ( )T ST Sr r

r r iS i ii T

D A n Em

φ ←← = ⋅∑

Same ”MIRD” Equation!!!Source is one voxelin the SPECT/PET image set

Target is one voxel inthe density image set

S values not pre-tabulated butcalculated when needed

Patient-specific geometry


POINT‐DOSE KERNELS – 3D

Describes specific absorbed fraction as function of radial distance from a point source.

Derived for homogeneous media (H2 O) using Monte Carlo calculations.photonsmono-energetic electronsβ-particlesRadionuclides


FULL MONTE CARLO CALCULATION – 3D

Energy deposition in 3D

Takes into account heterogenities in sources and tissues

May take considerable of CPU time

”Public Domain” programsEGS4,EGSnrcMCNPXGeant4Penelope........

90‐Y MCNP4 Simulation


3D DOSIMETRY BASED ON SPECT/PET

Absorbed dose calculation from local deposit energy, dose kernels or full Monte Carlo

are on a voxel level

Segmentation of organ volumes is not critical


3D-ID


RMDP (ROYAL MARSDEN)


THE LUNDADOSE

Include also methods for 3D SPECT/CT based dosimetry


Medical Radiation Physics, Lund Katarina Sjögreen-Gleisner, Michael Ljungberg, Karin Wingårdh, David Minarik, Sven-Erik Strand, Tomas Ohlsson

Department of Oncology, Lund Ola Lindén, Jan Tennvall

EXAMPLE: 3D BASED DOSIMETRIC STUDY IN LUND

High Dose Zevalin™ antibodies Non-Hodkin’s Lymphoma Dosimetry study - 111InTherapy study – 90Y Bremstrahlung ImagingBone-marrow supportAdministered activity based on absorbed dose (Gy)Maximum Tolerated Dose (MTD)


PROCEDURE

Seven multiple 111In SPECT/CT studies and WB studies

SPECT Reconstruction with OSEM iterative reconstruction algorithmPatient-specific correction for attenuation, scatter and collimator response

Image RegistrationCT-CT Based Non-Rigid Registration over multiple measurements. CT-CT transformations applied to SPECT-SPECT

Voxel based Absorbed Dose DistributionLocal absorbed energy (90Y)

LundAdose Software – written in IDL


ABSORBED DOSE IMAGES

90Y absorbed dose estimated from multiple quantitative 111-In images

Absorbed dose by numerical integration voxel-by-voxel after image registration

Masses from CT images


FUSED IMAGES

90Y absorbed dose estimated from multiple quantitative 111-In images

Absorbed dose by numerical integration voxel-by-voxel after image registration

Masses from CT images


REGIONS OF INTEREST


DOSE‐VOLUME HISTOGRAM

Dose calculationsAverageMedianAverage of 75% or aboveAverage of 90% or above

Gy / MBq

Estimation of necessary therapy activity is based on this value.


RADIOBIOLOGICAL PARAMETERS













Obtainbiokinetics

Obtainbiokinetics

Radiobiological Parameters

Hybrid SPECT/CT

Hybrid SPECT/CT


RADIOBIOLOGICAL PARAMETERS

RBE-weighted DoseConsider differences in Radiobiological effect for different types of radiation

Biologically Effective DoseAccounts for dose rate variations in radionuclide therapyBased on Linear-Quadratic Response ModelInclude α/β and rate-of-repair of sublethal damages.

Equivalent Uniform DoseSpatially varying absorbed dose distribution converted into an equivalent uniform absorbed dose that yield a biologic response similar to that expected from the nonuniform dose distribution.

Isoeffective DoseEquivalent absorbed dose of low-LET radiation that when delivered would produce the same clinical effects as the high-LET treatment.

"MIRD pamphlet No. 21: a generalized schema for radiopharmaceutical dosimetry--standardization of nomenclature." J Nucl Med 2009 50(3): 477-484.


PROBLEMS WITH MACROSCOPIC MONTE CARLO

Even if a voxel‐based Monte Carlo dosimetry approach that is properly

done is a improvement over organ‐based dosimetry – we still do not know the distribution of activity within the the

target voxel!!!


CONCLUSION

Dosimetry in Nuclear Medicine is a real challenge ☺

New hybrid SPECT/CT systems have significantly improved the accuracy in activity quantitation

Dosimetry on SPECT voxel level possible

Inherent spatial resolution problem may need connection to models describing activity distribution of small-scale levels

Radiobiological parameters will complement the physical ’absorbed dose’


THANK YOU FOR YOUR ATTENTION

Lund University, Sweden

http://upload.wikimedia.org/wikipedia/commons/f/fc/Lunds_universitets_huvudbyggnad_%28juli_2008%29.jpg

IMAGE-BASED PATIENT-SPECIFIC DOSIMETRY FOR RADIONUCLIDE THERAPY�Slide Number 2THE ”MIRD” EQUATIONSlide Number 4Slide Number 5Slide Number 6Slide Number 7Slide Number 8BIOKINETICS TO OBTAIN CUMULATED ACTIVITYSlide Number 10Slide Number 11Slide Number 12Slide Number 13Slide Number 14PRINCIPLES OF THE ML-EM ALGORITHMABSORBED DOSE CALCULATIONS FROM SPECT/PET IMAGESSlide Number 17Slide Number 183D DOSIMETRY BASED ON SPECT/PET3D-IDRMDP (ROYAL MARSDEN)THE LUNDADOSESlide Number 23Slide Number 24Slide Number 25Slide Number 26REGIONS OF INTERESTSlide Number 28RADIOBIOLOGICAL PARAMETERSRADIOBIOLOGICAL PARAMETERSPROBLEMS WITH MACROSCOPIC MONTE CARLOSlide Number 32THANK YOU FOR YOUR ATTENTION

Documents

IMAGE-BASED PATIENT-SPECIFIC DOSIMETRY FOR RADIONUCLIDE … · 2015. 3. 18. · Vienna, Austria. Medical Radiation Physics, Clinical Sciences Lund, Lund University BASIC DOSIMETRY