Integrated on-board CBCT-US imaging system for soft tissue IGRT and real-time intra-fraction monitoring

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Integrated on-board CBCT-US imaging system for soft tissue IGRT and real-time intra-fraction monitoring John Wong Radiation Oncology and Molecular Radiation Sciences Johns Hopkins University School of Medicine

Acknowledgments R Teboh Forbang --- Radiation Oncology M A Lediju Bell, H T Sen, P Kazanzides, I Iordachita Laboratory for Computational Sensing and Robotics U Hamper, R DeJong --- Radiology, Ultrasound Section D Ruben --- Comparative Medicine Technology P Xia, K Stephans, Y Zhong --- Cleveland Clinic M Lachaine --- Elekta, Soft Tissue Imaging Supported in part by: NCI R01 CA161613; Academia-Industry Research Partnership Elekta Sponsored Research Agreement

Challenges of Soft Tissue IGRT Inter-fraction methods: Cone beam CBCT, MV CT Pros Volumetric information Adaptive Radiation Therapy Cons Snap shot Ionizing radiation Image Quality Inter-fraction methods: Intra-modal ultrasound imaging Pros Soft tissue information Non-ionizing Cons Snap Shot (at present) Expertise/operator dependence Intra-fraction methods: Implanted Markers Real-time monitoring Invasive Pros Non-ionizing option Cons Ionizing radiation Soft tissue surrogate (truth?) Emergence of MRI-Radiation Machines

Integrated 3D ultrasound/cbct imaging for soft tissue IGRT Hypothesis: US-CBCT offers an nonionizing, non-invasive inter- and intra-fraction solution for soft tissue targets Prostate, liver, pancreas (a) CT only (b) CT with ultrasound

Challenges of US imaging Reproducibility / operator dependence Deformation of anatomy Soft tissue registration Solutions Robotic placement of a 3D probe Keep US probe in place during irradiation while avoiding beams Intra-fraction monitoring By definition, auto-fusion of CBCT and real-time US Require simulation/planning of patient in treatment position with the ultrasound/cbct system in place

SBRT Liver Planning Studies with Probe on Patient (n=10) Plan-Clinical Probe-Parallel Probe-Vertical

Liver SBRT Dosimetric Endpoint Comparing Plan-Clin US-Para US-Vert D95 - PTV 38.72 38.63 38.48 P>0.05 (Gy) ±0.14 ± 0.14 ± 0.31 V15 - Liver 363 355 367 P>0.05 (cc) ± 38 ± 48 ± 39 Except for the superficial lesions of 2patients, the remaining 8 can be treated with probe in place. Probe-parallel allows 7 coplanar/1 non-coplanar treatments Probe-vertical allows 2 coplanar/6 non-coplanar treatments

CT artifacts from Ultrasound Probe Need a model probe to avoid planning CT artifacts for planning and CBCT setup Require probe exchange Need to demonstrate reproducible placement and deformation

Reproducibility of model probe using CT: Passive (1D) robotic arm and gel phantom Model probe Vernier scale compressor Deformable gel phantoms with 12 embedded PMMA beads (1.2, 2.8, 3.2 mm in diameter) Compression Force ~ 5 N (~0.5 kg)

Reproducibility studies with model probe BB2 BB2 CT (1 mm) slice scans of repeat cycles of w/wo compression Intra-scan: Compare displacement due to compression Inter-scan (1 day apart): Compare the difference of two separate measurements after accounting for setup error All beads positions were reproducible to within 1 mm

Workflow: Robotic Assistance Treatment Planning Place US probe with robot for imaging Robot records position and force information Position patient on couch Treatment Delivery Align patient with lasers Acquire CBCT, compare to simulation & adjust couch based on bony anatomy Substitute US imaging probe with model probe Place US probe with robot using recorded position and forces Acquire CT simulation image with deformed tissue Treatment planning Real-time monitoring with US probe

Cooperatively Controlled Robotic Placement force sensor Measured force (applied by user) K Desired velocity (to robot controller) Cooperative Control (no virtual fixtures) Safety concerns regarding autonomous motion The need to adjust for setup error, anatomical changes, etc. Human operator will be involved Implementation of virtual fixtures: Enable less-skilled user to reproduce deformation (e.g., similar position/force) during inter-fraction treatment

Cooperative Robotic Arm for Probe Placement

Prototype Cooperative Robot for Probe Placement 2-Active Degree of Freedom Rotary Stage Passive Arm 3-Active Degree of Freedom Linear Stage Orthogonal Probe Positioning

R&D Robot GUI: Study of positional or force control

Ex-vivo Bovine Liver in gel phantom Gel phantom was overly simplistic with uniform deformation A more realistic ex-vivo liver phantom was devised Comparison of deformation was made between ultrasound and model probe.

Reproducibility of Deformation Contact forces lower with model probe The robotic arm needs to be stiffened Significant compression force differences between gel and liver phantom Suitability of phantom material is of concern 8/5/2013 20

X-ray CT Ultrasound IGRT : In vivo feasibility studies DO13M143: Reproducibility of probe placement for combined US-CT imaging Most realistic subject Reproducibility of induced deformation Between clinical US probe and model probe Intra-fraction during a treatment/simulation session Inter-modality from simulation to treatment Inter-fraction on different days (analysis in progress)

DO13M143 Laboratory dogs: 4 planned, 1 studied Three spherical stainless steel markers (2.38 mm dia) implanted in the prostate, liver, pancreas 1-2 organs were studied per week Helical CT of displaced marker positions due to robotic placement of imaging and model probe no probe, imaging probe, model probe Focus of first dog study over 4 weeks: Workflow; system configuration; Intra-fraction variation

8/5/2013 23

Prostate (Force = 14 N)

Prostate Images Ultrasound CT with real probe CT with model probe

Reproducibility (mm) Reproducibility (mm) Reproducibility (mm) Prostate (Force = 14 N; 10 N ~ 1 kg): Marker Position Reproducibility in Interquartile Range 2 Real Probe: 3D mean error=0.6 mm Model Probe: 3D mean error = 0.7mm 1 1 0.5 0 0 LR AP SI LR AP SI No Probe: 3D mean error = 0.4mm 0.6 0.4 0.2 0 LR AP SI

Prostate: Probe-Induced Marker Displacement (from no probe) 3D mean error = 0.2mm

Liver at Breath-hold (Force = 40 N)

Liver CT and Ultrasound Images

Reproducibility (mm) Reproducibility (mm) Reproducibility (mm) Liver (Breath-hold): Marker Position Reproducibility in Interquartile Range 0.4 0.3 0.2 0.1 0-0.1 Real Probe: 3D mean error=0.3 mm 0.4 0.3 0.2 0.1 0-0.1 No Probe: 3D mean error = 4.7mm Model Probe: 3D mean error=0.6 mm 5 0

Liver (at Breath-hold): Probe-Induced Marker Displacement 3D mean error = 4.1 mm

Pancreas (Force = 34.5N)

Reproducibility (mm) Reproducibility (mm) Marker Displacement Reproducibility (mm) Reproducibility (mm) Pancreas (at Breath-hold): Probe-Induced Marker Displacement Real Probe: 3D mean error = 1.6 mm 2.5 2.0 1.5 1.0 0.5 0 2.5 2 1.5 1 0.5 0 LR AP SI 1.5 1.0 0.5 0 Model Probe: 3D mean error = 1.1 mm 1.5 No Probe: 3D mean error = 1.3mm 1.0 0.5 0

Pancreas (at Breath-hold): Probe-Induced Marker Displacement 3D mean error = 4mm

Conclusions CT of implanted markers provides a direct validation of reproducible deformation due to probe Choice of phantom is important to study reproducibility for ultrasound guidance (Force: 1 to 40N) Prostate deformation is reproducible to within 1 mm Results for liver and pancreas can be improved Experience; no visual feedback; un-optimized system More in vivo (dog) IGRT studies to: refine the system Inter-fraction study on a CBCT machine

Robot System Requirements Repeatable mounting of US probe and model probe Record probe position and contact force (in simulation) Enable operator to reproduce position and force when switching between US and model probes Hold model probe in place during CT or CBCT acquisition Enable less-skilled user to reproduce deformation (e.g., similar position/force) during inter-fraction treatment Hold US probe in place during treatment Sufficient workspace to scan abdominal organs: prostate, liver, kidney, pancreas (as we discover!!!)

Volume (%) Dose Volume Histograms US Probe in Plans PTV Clinical Plan Health Liver Kidney Dose (cgy)