992020 Patient Position Verification Using Pencil Beam Radiography

9/9/2020 Patient Position Verification Using Pencil Beam Radiography and Markers Lucas Huber 1, Julia Telsemeyer 1, 2, Bernadette Hartmann 1, 2, Maria Martisikova 1, Oliver Jäkel 1, 2, 3 1 Research Group Heavy Ion Therapy, German Cancer Research Center 2 University Clinic Heidelberg 3 HIT Heidelberg Ion Therapy Center 9/9/2020 | Page 1 Lucas Huber Research Group Heavy Ion Therapy

Outline of the Talk I. Heavy Ion Therapy 1. Rationale for Heavy Ion Therapy 2. Beam Application at the Heidelberg Ion Therapy Center 3. Patient Position Verification II. Ion Beam Radiography 1. Motivation 2. Investigations with the Flat-Panel and Metal Markers 3. Scattering Reduction 4. Pencil Beam Radiography III. Summary and Conclusions 9/9/2020 | Page 2 Lucas Huber Research Group Heavy Ion Therapy

I. HEAVY ION THERAPY (Gantry treatment room at HIT, university clinic HD, HIT-brochure) 9/9/2020 | Page 3 Lucas Huber Research Group Heavy Ion Therapy

Rationale for Heavy Ion Therapy Compared to photons: • Advantageous inverse dose profile of ions • Increased biological effectiveness of heavy ions in Bragg peak Conventional therapy Tumor Ion therapy Tumor Dose deposition (Image from Christoph Bert‘s lecture on treatment planning 2011) 9/9/2020 | Page 4 Lucas Huber Research Group Heavy Ion Therapy

Acceleration and Beam Application at HIT • Synchroton allows for active beam application using the Rasterscanning technique Pencil Beam 9/9/2020 | Page 5 Lucas Huber Research Group Heavy Ion Therapy

Patient Positioning Verification • Precise dose application in ion therapy → Exact knowledge of patient position is crucial • Current clinical routine for positioning: 2 perpendicular X-ray projections before treatment • Future treatment of moving tumors needs modality to acquire tumor position information (Images from university clinic HD, HIT press release 2010) 9/9/2020 | Page 6 Lucas Huber Research Group Heavy Ion Therapy

II. ION BEAM RADIOGRAPHY 9/9/2020 | Page 7 Lucas Huber Research Group Heavy Ion Therapy

Motivation for Ion Radiography • Inverse dose profile allows for high contrast between small range differences • Each ion leads to energy deposition in detector • Very good detection efficiency • Using carbon ions leads to intrinsic scattering reduction compared to lighter particles 9/9/2020 | Page 8 Lucas Huber Research Group Heavy Ion Therapy

The Flat-Panel Detector RID 256 -L (Perkin Elmer, Wiesbaden, Germany) • 256 x 256 pixel a-Si: H p-i-n photodiodes and thin • • • film transistors Lanex Fast Back® 2 mm aluminium shielding Read-out: 12. 5 Hz Pixel size: 0. 8 x 0. 8 mm 2 Sensitive area: 20 x 20 cm² • No signs of radiation damage so far (Courtesy of Bernadette Hartmann) 9/9/2020 | Page 9 Lucas Huber Research Group Heavy Ion Therapy

Metal Markers (image from Medscape. com) • Precise spatial definition and high range difference • Have to be placed inside or right next to the tumor • Usually inserted with biopsy needle and US image guidance • Cause CT artifacts Metal Markers used in Measurements: • Nitinol Marker, Ni. Ti-alloy, cylinder Ø 1. 1 mm, length 5 mm • Gold Anchor® , Au, segmented filament Ø 0. 27 mm wax (Gold Anchor® webpage) 9/9/2020 | Page 10 Lucas Huber Research Group Heavy Ion Therapy 1 cm

Metal Markers: Contrast wax • Idealized Patient Setup: Detector Signal [au] C, E = 300. 0 305. 3 Me. V/u 304. 2 303. 2 302. 1 301. 1 • Energy → Detector in peak region • Best contrast is yielded by placing the marker behind the peak C, E = 300. 0 305. 3 Me. V/u 304. 2 303. 2 302. 1 301. 1 Energy of Initial Particle [Me. V/u] Absolute Contrast Energy of Initial Particle [Me. V/u] 9/9/2020 | Page 11 Lucas Huber Research Group Heavy Ion Therapy

Scattering: Contrast in Depth Contrast [px] Traversed Depth in PMM [px] 300 Me. V/u 9/9/2020 | Page 12 [px] Lucas Huber (wax contributes as ~0. 5 cm PMMA) Research Group Heavy Ion Therapy

Using a Range Shifter: Stopping material between imaging volume and detector Increased energy leads to: • Decrease in dose to the imaging volume • Less scattering in imaging volume Equivalent Length in PMMA [cm] Water PMMA Using denser material as range shifter: • Scattering spread reduction R 0 in cm water 9/9/2020 | Page 13 Lucas Huber Research Group Heavy Ion Therapy Cu W

Scattering Reduction: Measurements • PMMA range shifter setup: C 392 Me. V/u PMMA Cu • Cu range shifter setup: C 391 Me. V/u 9/9/2020 | Page 14 Lucas Huber Research Group Heavy Ion Therapy

Pencil Beam Radiography Use single pencil beam on assumed marker position • Typical focus width • Contrast high enough for good visibility despite field gradient of pencil beam [px] • Applies dose only to small volume [px] Marker 9/9/2020 | Page 15 Lucas Huber Research Group Heavy Ion Therapy displaced by 2. 0 mm

Dose versus Signal to Noise Ratio [px] reference [px] • Necessary particles for good [px] C 391 Me. V/u °Poisson noise based on reference image visibility: • Mean dose per single carbon in irradiated volume SNR → Dose Incident Particle Number 9/9/2020 | Page 16 Lucas Huber Research Group Heavy Ion Therapy

IV. SUMMARY AND CONCLUSION (image : university clinic HD, HIT-brochure) 9/9/2020 | Page 17 Lucas Huber Research Group Heavy Ion Therapy

1. Summary • Markers can yield very high contrast • Using additional range shifter decreases scattering spread • Pencil beam radiography can yield position information of resolution below 1 mm • Imaging dose with current setup rather high 9/9/2020 | Page 18 Lucas Huber Research Group Heavy Ion Therapy

2. Conclusion • Pencil beam radiography is a promising imaging technique for tumor position verification • Necessary imaging dose has to be further reduced possibilities: • using higher energies • normalization of fluence and angle detection • For this purpose we are further investigating the Timepix layout of the Medipix 2 detector 7. 7 mm [px] Medipix measurement in cooperation with Carlos Granja and Jan Jakubek from CVUT, June 2011 9/9/2020 | Page 19 Lucas Huber Research Group Heavy Ion Therapy

Thank you for your interest! 9/9/2020 | Page 20 Lucas Huber Research Group Heavy Ion Therapy

Metal Markers: Radiographies 300 Me. V/u C ~300 Me. V/u 303 Me. V/u 305 Me. V/u E Absolute Signal • Energy → Detector signal in peak region • Markers are represented by only 10 20 pixels on the detector Dynamic Range Signa 9/9/2020 | Page 21 Lucas Huber Research Group Heavy Ion Therapy

Scattering: Air Gap Effect w • Air gaps have strong influence on scattering spread: • Exit angular spread gets scaled with air gap length w 9/9/2020 | Page 22 Lucas Huber Research Group Heavy Ion Therapy

Realistic Setup: Alderson Phantom • Single slice orthogonal to beam • Two projections taken • Marker is visible but peak contrast much more present in image due to gradient of the material thickness in lateral direction E 224 E 225 E 226 E 227 9/9/2020 | Page 23 Lucas Huber Research Group Heavy Ion Therapy

Scattering in Marker Radiography C 89 Me. V/u P 44 Me. V • Highest signal difference for straight lines at peak position of neighborhood • But scattering also influences contrast because width of marker • MC simulation: Lateral energy distribution C, energy 314 Me. V/u, in PMMA, Ni marker at 7. 5 cm 9/9/2020 | Page 24 Lucas Huber Research Group Heavy Ion Therapy

Scattering (source: Scientific Lectures, Multiple Coulomb Scattering) MCS theory by Rossi /Greisen: In small angle approximation * schematic Bragg curve 190 Me. V p σ [cm] (230 Me. V p) 350 Me. V /u C For further calculations the linear displacement approximation in the formulation given by Kanematsu was used for the scattering power: 9/9/2020 | Page 25 Lucas Huber Research Group Heavy Ion Therapy R [cm]

II. iii. Scattering Reduction: Copper RS Setup Measurements PMMA Cu 9/9/2020 | Page 26 Lucas Huber Research Group Heavy Ion Therapy

Scattering Reduction: Range Shifter (RS) Basic ideas: Energy increase leads to: • Decrease in dose to the imaging volume Use of high stopping power material as range shifter: • Allows for overall scattering spread reduction 9/9/2020 | Page 27 Lucas Huber Research Group Heavy Ion Therapy

Scattering Reduction: Comparing Range Shifter Materials • Calculating σ² of an incident pencil beam after traversing an imaging volume and additional range shifter • condition that the detector is placed directly at the range end L Water • Important quantities: ρ, X PMMA Higher energy leads to less scattering in imaging volume, while high ρ material decreases length of transport Copper Tungsten R 0 in cm water 9/9/2020 | Page 28 Lucas Huber Research Group Heavy Ion Therapy

9/9/2020 | Page 29 Lucas Huber Research Group Heavy Ion Therapy

“Realistic“ Setup: Alderson Phantom 9/9/2020 | Page 30 Lucas Huber Research Group Heavy Ion Therapy

Additional Material • Depth dose profiles of ion beams: Influence of inelastic collisions with atomic electrons Bethe-Bloch equation describes energy loss (d. E) of ions per path length (dx): 9/9/2020 | Page 31 Lucas Huber Research Group Heavy Ion Therapy