PET/CT multimodality imaging for radiotherapy planning in lung cancer The medical physicist point of view Isabelle Gardin Rouen CHB and Quant.I.

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1 PET/CT multimodality imaging for radiotherapy planning in lung cancer The medical physicist point of view Isabelle Gardin Rouen CHB and Quant.I.F (EA4108 FR CNRS 3638)

2 Outline Specific acquisition conditions Dose painting by contour Segmentation of PET positive tissue Dose painting by numbers Comparison of DPBN vs. DPBC Data transfert 2

3 Specific acquisition conditions To ensure the target will received the prescribed dose by imaging the patient in the exact position in which therapy will be delivered The patient must be positioned the same way than during the treatment on a flat table Similar to the LINAC treatment table Locked in place in the scanning bed Possibility to place various immobilization devices 3

Specific acquisition conditions Necessary to have 3 positioning lasers to align the patient with wall mounted lasers to ensure the patient position is unchanged with each daily

4 Specific acquisition conditions Necessary to have 3 positioning lasers to align the patient with wall mounted lasers to ensure the patient position is unchanged with each daily treatment. Installed on the ceiling and both opposing walls of the PET/CT scanning room Sited according to PET/CT gantry isocenter Quality control procedure and possibility of setting 4

Specific acquisition conditions Necessary to achieve indelible reference points on the patient s skin with the laser cross-beams correlating

5 Specific acquisition conditions Necessary to achieve indelible reference points on the patient s skin with the laser cross-beams correlating with the table position All these experiments have to be done by trained technologists for treatment security and to limit radiation hazards 5

6 Specific acquisition conditions Radiotracer administration (FDG, FMizo,etc ) The same protocol than for diagnostic PET The same acquisition parameters than for diagnostic 1 or 2 table positions for radiation therapy planning alone WB scan is also possible Possibility of gated acquisitions PET, PET/CT if available 6

7 Specific acquisition conditions CT (PET/CT acquisition) Case 1: CT used for radiation therapy simulation Same acquisition and reconstruction conditions: Slice thickness, etc Contrast injection if necessary No influence of contrast agent on SUV measurement (Vera Radiother Oncol 2013) Needs a calibration of the CT in case of dosimetry computation using compensation of density heterogeneity Case 2: CT not used for radiation therapy simulation Needs a co-registration of TEP/CT to the simulation CT Experience from CHB CT (PET/CT) used for radiation therapy simulation Patient positioning by both a radiation therapy technologist and a trained PET/CT technologist 7

Dose painting by contour: Definition of DP Prescription of a non uniform dose distribution (Hall, The Lancet Oncology 2005) within the tumor volume based on Biological Target Volumes BTV, (Ling et

8 Dose painting by contour: Definition of DP Prescription of a non uniform dose distribution (Hall, The Lancet Oncology 2005) within the tumor volume based on Biological Target Volumes BTV, (Ling et al, Radiotherapy and Oncology 2000) corresponding to glucose metabolism (FDG) and/or tumor hypoxia (FAZA, FMizo, etc ) The aim: to minimize the risk of relapse while respecting dose constraints to Organs At Risk (OAR) 8

9 Dose painting by contour Principle of Dose painting by contour (DPBC) To have a higher radiation dose in BTV than in the surrounding tumor volume 9 How to segment the lesion on PET images? Meijer Radiother Oncol 2011

10 PET segmentation No consensus on the best method of PET positive tissue segmentation (Zaidi EJNMMI 2010) Manual delineation Most intuitive Gold standard Often the only one available Time consuming Inter and intra-observer variability Large source of errors 10

11 PET segmentation Automatic or semi-automatic methods Thresholding Watersheds Clustering Random walk Etc. 11

12 PET segmentation: Constant threshold values 40% of SUV max (Erdi et al. Cancer, 1997) 2.5 (Nestle et al. J Nucl Med 2005) Example FDG PET SUV max = 30 Th opt = 40% SUV max For large lesions (> 3 FWHM) Well contrasted (SUV max >3) Not heterogeneous Th opt = 2.5 Threshold of 40% of SUV max Good compromise 12

13 PET segmentation: Adaptative thresholding methods The optimal threshold cannot be a constant. It depends on: Tumour size Local contrast Reconstruction protocol Etc Needs a calibration procedure 13

14 PET segmentation: Adaptative thresholding method Iterative definition of the optimal threshold Th n Volume V n Contrast C n yes Th n =Th n+1 Th n+1 Th n Th n+1 no Th n+1 = Optimal threshold Th n+1 C n Centre Henri-Becquerel

Phys 2004 Th opt = C 1 *SUV + C 2 Vauclin Phys

15 PET segmentation: Adaptative thresholding method Erdi et al. Cancer 97 Daisne et al. Radiother and Oncol 2003 Th opt = B 1 + B 2 /Contrast Black et al. Int J Radiation Onc Bio. Phys 2004 Th opt = C 1 *SUV + C 2 Vauclin Phys Med Biol 2009 ; Doyeux Nucl Med Commun 2013 Centre Henri-Becquerel

16 PET segmentation: Watersheds Needs an image pre-processing Raw image Denoised image Deblurred image Gradient magnitude Watersheds Clusters Contours 16 Courtesy J.Lee Geets et al. EJNM 2007 (ORL) Wanet et al. R&O 2011 (CPNPC)

17 PET segmentation: Method based on clustering Example of 3D-MIP Theory of possibilities or fuzzy logic VOI 1 Volumes after information fusion VOI BG 1 PET Volume 2D MIP classification Possibility theory VOI 2 Fusion BG Decision rules Result 17 3 MIP Images Courtesy M.Vermandel BG 2 Map of degree to Corresponding belong: lesion and volumes background Dewalle-Vignon et al. IEEE Trans Med Imaging 2011

18 PET segmentation: Method based on clustering Other methods based on the principle of voxel clustering GMM (Gaussian mixture model) Aristophanous et al Med Phys 2007 FLAB (Fuzzy Loccally Adapative Bayesian) Hatt et al IEEE Trans Med Imag 2009 SECM (Spatial Evidential C-Means) Lelandais et al MICCAI 2012, Med Image Analysis

19 PET segmentation: Random Walk Example with Locally Adaptative Random Walk: 3D-LARD: Onoma IEEE ISBI 2012 Efficient to segment small or heterogeneous lesions: Comp Med Imag Graphics 2014 Manual Segmentation 3D-LARW segmentation 19

20 PET segmentation: Problem of movement Gated acquisition 20

Error (ml) Amplitude (%) 100 80 60 40 20 0 0 5 10 15 20 Temps (s) PET segmentation: Problem of movement

21 Error (ml) Amplitude (%) Temps (s) PET segmentation: Problem of movement Ungated acquisition M Error of volume measurements on ungated vs gated acquisitions VDun VD5 21

22 Dose painting by numbers Principle of Dose painting by numbers (DPBN) Definition of a prescription function between the voxel intensity and the dose: The dose is adjusted on a voxel-to-voxel basis What prescription function has to be used? 22 Meijer Radiother Oncol 2011

23 Dose painting: DPBN Prescription function Linear relationship between the voxel intensity and the prescribed dose (Bentzen, Radiat Oncol 2011): D(SUV)= D min + (D max -D min )*(SUV-SUV min )/(SUV max -SUV min ) The most intuitive Easy Other solution: Sigmoid 23 Thorwarth Nucl Med Review 2012

Dose painting: DPBN Prescription function SUV is a poor representation of the real amount of 18 F at the voxel level due to a lot of noise, partial volume effect and possibly a low S/N ratio

24 Dose painting: DPBN Prescription function SUV is a poor representation of the real amount of 18 F at the voxel level due to a lot of noise, partial volume effect and possibly a low S/N ratio (hypoxia) We have proposed to use the amount of belief that the voxel belongs to the lesion using the belief function theory ( Lelandais, Med Imag Analysis 2014) 18 F-FDG 18 F-FLT 18 F-FMISO Distribution of the SUV in PET images Maps of the distribution of the belief to belong to the tumor 24 Metabolism Proliferation Hypoxia

structures One needs to define isocontours compatible

25 Dose painting: DPBN Prescription function Treatment Planning Systems (TPS) handle volumes and not voxels: RT structures One needs to define isocontours compatible with: RT structures on the TPS FDG 25 Meijer Radiother Oncol 2011

26 Dose painting: DPBN Prescription function Treatment Planning Systems (TPS) handle volumes and not voxels: RT structures One needs to define isocontours compatible with: The performances of the LINAC: Tolerance of dose gradient IMRT no more than 20 Gy/cm (VARiAN) 26 Choi Radioth Oncol 2010

27 Comparison of DPBN vs. DPBC 10 patients Stage II/III lung cancer - FDG Both strategies possible 3/10 patients with small peripherical tumor For the others the boost dose was confined by a critical structure. Higher dose was possible with DPBN 50% SUVmax 27 Meijer Radiother Oncol 2011

28 Data transfer: In a clinical context PET/CT images Transfer of PET/CT images from the PET/CT workstation to TPS DICOM 3 via network connections or hard copy disc Normally easy to do But, due to the treatment security, all the data must be associated to the planning CT If this CT comes from the PET/CT => Easy If there are 2 CTs (planning CT and PET/CT) => Be aware of this problem 28

29 Data transfer: In a clinical context RT structures Transfer of BTV from the PET/CT workstation to TPS or virtual simulation station DICOM RT via network connections or hard copy disc Most of the time, TPS have not the good tools for BTV segmentation Impossibility to convert PET voxel intensity in SUV Necessity to transfert BTV as RT structure Can be difficult to have DICOM RT tools available Can be a nightmare 29

30 Data transfert: In a multicenter clinical trial CHB PET/CT FDG 1 + GTV m Decision of F-miso 1 positif PET/CT F-miso 1 + GTV h DICOM RT compatible Data exchange capability Distance functions Visualisation Filling forms SFMNET-KEOSYS MN PET/CT FDG 1 PET/CT F-miso 1 PET/CT FDG 2 PET/CT F-miso 2 TEP/TDM Follow up 3 mth CT MEP dosimetry < 48 h PET/CT Follow up1 y RT 30 Segmentation BTV(FDG, FMiso)

31 Thank you for your attention 31 31

ICARO Vienna April Implementing 3D conformal radiotherapy and IMRT in clinical practice: Recommendations of IAEA- TECDOC-1588

ICARO Vienna April Implementing 3D conformal radiotherapy and IMRT in clinical practice: Recommendations of IAEA- TECDOC-1588 ICARO Vienna April 27-29 2009 Implementing 3D conformal radiotherapy and IMRT in clinical practice: Recommendations of IAEA- TECDOC-1588 M. Saiful Huq, Ph.D., Professor and Director, Dept. of Radiation