Application of 3D Printing to Molecular Radiotherapy Phantoms. Nick Calvert Nuclear Medicine Group The Christie NHS Foundation Trust, Manchester

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1 Application of 3D Printing to Molecular Radiotherapy Phantoms Nick Calvert Nuclear Medicine Group The Christie NHS Foundation Trust, Manchester

2 Molecular Radiotherapy Radionuclide administered to patient in form of radiopharmaceutical. Radiopharmaceutical consists of radioactive isotope & vector that binds to lesions. (e.g. Lutetium- DOTATATE for NETs) Uptake in lesions and healthy tissue. Currently empirical activity is typically administered. Evidence suggests correlation between dose delivered and treatment outcome [1]. (MRT)

3 SPECT Imaging Distribution of administered activity Rotation Rotation SPECT scanner consists of two detector heads, each containing a collimator, scintillator panel and number of PMTs. Technology is currently moving towards semiconductor detectors.

4 SPECT Imaging Distribution of administered activity Rotation Rotation Collimator restricts angle of incoming photons, assuming no scatter.

SPECT Imaging Distribution of administered activity Rotation Image Reconstruction Rotation Reconstruct counts in each voxel insufficient

5 SPECT Imaging Distribution of administered activity Rotation Image Reconstruction Rotation Reconstruct counts in each voxel insufficient to perform dosimetry. Number of corrections are required for quantitative SPECT imaging. Aim is to calculate the activity in each voxel.

Quantitative SPECT Imaging SPECT Convert to Activity Sum over voxels in VOI Estimate of activity in each organ of interest CT Draw VOIs Convert from counts to

6 Quantitative SPECT Imaging SPECT Convert to Activity Sum over voxels in VOI Estimate of activity in each organ of interest CT Draw VOIs Convert from counts to activity in each voxel. Conversion requires a calibration factor (cf = counts/ (activity x time)). Draw VOIs around organs/lesions to get total activity in each region.

7 Quantitative SPECT Imaging Quantitative SPECT is reliant upon: Calibration factor(s). Collimator choice. Injected activity/acquisition time. Number of views. Energy windows. Image reconstruction method. Attenuation & scatter correction. Partial Volume Correction. Collimator-detector (resolution) response correction. 3D printing allows us to test these on realistic phantoms, measure accuracy of quantitative SPECT imaging, and validate clinical practice. Previously used spherical/regular shaped test objects.

8 Activity (MBq) SPECT MIRD-based Dosimetry Time point 1 Time point 2 Time point 3 Time point 4 Time point 5 Time Activity Curve Time (hours) CT Integrate to get the time integrated activity curve (total number of nuclear transformations) A r s, T D. Dose in each target organ, r T, is D r T, T D = r S A r s, T D S r T r S where r S is the source organ, and S r T r S is the S- factor, describing the absorbed dose in r T per decay in r S. [2]

9 3D Printed Phantoms Requirements: Hounsfield units should match water/soft tissue or bone. Must be watertight. Clear/opaque to help with filling. Strong Liver can be several litres in volume. Should not react with compounds used in MRT.

10 MIRD Organs Data from [3]. Shapes defined in [4] (designed in 70 s & 80 s)

11 MIRD Organ-Specific Calibration Factors Data from [3]

12 MIRD Limitations Patient 1 Patient 2 MIRD ICRP110 How representative are mathematical models to patient data? Shape & size of organ affects calibration factor in SPECT image.

ICRP110 Voxel Phantom Average male/female. CT of individual was segmented, then scaled to ensure height & skeleton mass match reference male/female.

13 ICRP110 Voxel Phantom Average male/female. CT of individual was segmented, then scaled to ensure height & skeleton mass match reference male/female. Voxels were added/subtracted to organs to ensure mass matched reference & then voxels were added/subtracted to adipose tissue to ensure total mass matches reference. Voxel size x x 4.84 mm places limit on resolution of organs. Accepted as dosimetry standard.

14 ICRP110 Voxel Phantom Smooth mesh (MATLAB) Voxels Convert to mesh (MATLAB) Extrude mesh to create walls. Add filling ports. Slice, etc. (Meshmixer & Netfabb)

Insert activity ratios calculated from clinical data

15 ICRP110 Printed Phantom Printed in PLA on Ultimaker 2. Inserts filled with 99m Tc/Saline mixture. Insert activity ratios calculated from clinical data (median of 12 patient dataset). Imaged on GE Discovery NM/CT 670 Pro.

16 ICRP110 Printed Phantom First scan of Christie ICRP inserts, using existing phantom ellipse which is too large. Kidneys have two compartments: Cortex & Medulla (including Pelvis). Kidney activity concentration ratios (Cor:Med): 2:75:1 (LK) & 2.74:1 (RK) Kidney counts per voxel ratios (Cor:Med): 1.06:1 (LK) & 0.95:1 (RK)

17 ICRP110 Printed Phantom Cortex Medulla First scan of Christie ICRP inserts, using existing phantom ellipse which is too large. Kidneys have two compartments: Cortex & Medulla (including Pelvis). Kidney activity concentration ratios (Cor:Med): 2:75:1 (LK) & 2.74:1 (RK) Kidney counts per voxel ratios (Cor:Med): 1.06:1 (LK) & 0.95:1 (RK)

18 Measured Activity Concentrations Insert Activity Concentration (MBq/mL) Liver LK Cortex LK Medulla RK Cortex RK Medulla Spleen Recorded mean Counts per Voxel Results are (very!) preliminary. LK Summed RK Summed

Introduce an interchangeable cap for the Liver with fillable tumours of varying size/shape.

19 ICRP110 Printed Phantom Next Steps Organs are joined (LK & Spleen and RK & Liver) to ensure position and orientation remain constant and measurements are repeatable. Introduce an interchangeable cap for the Liver with fillable tumours of varying size/shape. 3D print or cast a torso shape rather than an elliptical tube to contain the inserts. Printed scale model.

20 Patient Specific Phantoms - CATIE Christie Anthropomorphic Tomographic Imaging Ellipse (CATIE) Segmented CT CAD Printed Phantom

21 Patient Specific Phantoms - CATIE Patient scan CATIE scan

Patient Specific Phantoms With Tumours Patient dataset printed with two Hepatic lesions permanently attached to Liver. Volumes: 37.11 ml & 12.23 ml.

22 Patient Specific Phantoms With Tumours Patient dataset printed with two Hepatic lesions permanently attached to Liver. Volumes: ml & ml. Tumours defined by VOI so should be realistic size/shape. Can be used to validate dosimetry software (OLINDA/EXM does not consider cross-dose from lesions).

23 Patient Specific Phantoms With Tumours Patient had other Hepatic lesions that have not been outlined or printed. Planning on reprinting with necrotic tumours printed as well.

24 Tumour Library Starting to build up a library of tumours, from patient CTs and mathematical shapes. Mount internally and externally. Investigate effect on dosimetry results. Previously only used spheres as a model for tumour. Necrotic centres.

25 Advantages of 3D MRT Phantoms Cheapish (depending on material). Easy Fast Printed parts easily replaceable STL can be used as an ideal outlining tool (assuming no significant shrinkage of model). STL can be imported to Monte Carlo toolbox GATE for validation simulations.

26 Disadvantages of 3D MRT Phantoms Phantoms can be large and difficult to fill. Dosimetry requires multiple fillings Some dose to operator. Difficult to achieve non-uniform activity distribution(s).

27 3D Printed Models in GATE (Monte Carlo) SPECT Scanner Head Torso Liver R Kidney L Kidney Spleen SPECT Scanner Head Able to replicate scanner geometry & printed models by directly importing.stl files into GATE. Provide better estimate of dose & validate dosimetry methods.

28 Acknowledgements Thanks to: Dave Hamilton, The Christie NHS Foundation Trust Jill Tipping, The Christie NHS Foundation Trust Emma Page, The Christie NHS Foundation Trust Dave Cullen, University of Manchester Ben Pietras, University of Manchester Emlyn Price, University of Manchester Andrew Robinson, NPL This work was supported by the European Metrology Programme for Innovation and Research (EMPIR) joint research project 15HLT06 "Metrology for clinical implementation of dosimetry in molecular radiotherapy" (MRTDosimetry; which has received funding from the European Union. The EMPIR initiative is co-funded by the European Union's Horizon 2020 research and innovation programme and the EMPIR Participating States. Work presented was also supported by STFC IPS [ST/P000150/1], STFC Case [ST/I006188/1], and STFC Mini-IPS [ST/M002918/1] awards.

29 References [1] Lidia Strigari et al. The evidence base for the use of internal dosimetry in the clinical practice of molecular radiotherapy. Eur. J. Nucl. Med. Mol. Imaging, 41(10): ,2014. [2] Yuni K Dewaraja et al. MIRD pamphlet No. 23: quantitative SPECT for patient-specific 3-dimensional dosimetry in internal radionuclide therapy. J. Nucl. Med., 53(8): , Aug [3] Andrew P. Robinson et al. Organ-specific SPECT activity calibration using 3d printed phantoms for molecular radiotherapy dosimetry. EJNMMI Phys., 3, Jul [4] M. Cristy and K.F. Eckerman. Specific absorbed fractions of energy at various ages from internal photon sources. Oak Ridge National Laboratory, Apr Thanks & Questions?

3D Printed Phantoms for MRT Dosimetry

3D Printed Phantoms for MRT Dosimetry Dr. Andrew Robinson Nuclear Physics Group, The University of Manchester Christie Medical Physics and Engineering, The Christie NHS Foundation Trust BIR/IDUG: The Future