Orthopaedic applications of MARS spectral CT Kishore Rajendran

Orthopaedic applications of MARS spectral CT Kishore Rajendran Department of Radiology, Centre for Bioengineering University of Otago, Christchurch New Zealand

MARS small-animal scanners Medipix All Resolution System (MARS) 2

Topics • CT imaging • Introduction to MARS technology – Medipix photon-counting detectors – Small-animal gantry system – Imaging routine (data acquisition, processing, and reconstruction) • Orthopaedic applications of MARS imaging – Metal implant imaging – Non-destructive characterization of 3 D-printed biomaterial scaffolds – Quantitative cartilage imaging for osteoarthritis • Summary and outlook 3

Computed Tomography • Mathematical foundation - Radon Transform, and Fourier Transform • First CT scanner - Godfrey Hounsfield (EMI Ltd) and Allan Cormack (Tufts Univ. ) 1971 First successful scan of a cerebral cyst 1979 Nobel Prize for Physiology and Medicine • Current technology: Multislice CT, Dual-energy CT, and Spectral CT (upcoming) • CT enables high resolution volumetric imaging for clinical and industrial applications. Recently, micro. CT has become popular for non-destructive imaging of samples at < 1 µm spatial resolution. 4

Computed Tomography Parallel-beam geometry Fan-beam geometry Cone-beam geometry • Cone-beam geometry enables multi-slice fast scans • Parallel-beam and fan-beam geometries are outdated, but are easy to implement computationally. 5

Computed Tomography: Spiral/Helical scans • Helical geometry enables fast whole body scans • Uses cone-beam geometry Image courtesy Siemens Healthcare JT Bushberg et. al, The Essential Physics of Medical Imaging, LW&W, 2002 6

Computed Tomography Io I • Lambert-Beer Law, I = I 0 e-µL • I (attenuated beam), Io (incident beam) and L (path length) are known, µ to be estimated • µ is the linear attenuation coefficient (material-specific and x-ray energy-specific) 7

Computed Tomography Io I Algebraic framework for reconstructing µ from transmitted x-ray data Ax = b A – ray geometry information x – volume data to be estimated (µ) b – Transmission data (measured line integral) Several algorithms have been devised since the 1970 s – ART, SIRT, OSEM 8

Spectral signatures of materials Conventional CT

Spectral signatures of materials Spectral CT Bin 1 Bin 2 Bin 3 Bin 4 Bin 5

Colour CT image Barium component Calcium component Analogy: Black and white TV (grayscale) vs. Colour TV 11

MARS Spectral CT • Multidimensional data with spatial, spectral, temporal components. Single energy CT – dual energy CT – multienergy CT (spectral) • Resolving x-ray energies attenuation spectra of materials quantification of native tissue types and contrast pharmaceuticals. • Spectroscopic x-ray detection enabled using Medipix photon-counting detectors developed at CERN. • Better x-ray detection efficiency (PCD) low radiation dose. • Can provide molecular information at high spatial resolution. 12

MARS small-animal scanners • Rotating gantry setup with Medipix detectors • Polychromatic x-ray source for diagnostic x-rays (10 to 120 ke. V) • Fully automated imaging chain (acquire, store, process, transfer, visualize) 13

Overview: MARS imaging routine 14

Medipix Energy-discriminating, pixelated detectors R. Ballabriga Suñé, “The design and implementation in 0. 13 m cmos of an algorithm permitting spectroscopic imaging with high spatial resolution for hybrid pixel detectors, ” Ph. D. dissertation, Ramon Llull University, Barcelona, Spain, 2009. 15

MARS detector module ASIC Sensor layer Readout Medipix. MXR Silicon Medipix 3. 0 Gallium arsenide MARS camera V 5 (ILR Christchurch) Medipix 3. 1 Cadmium telluride Medipix 3 RX Cadmium zinc telluride (CZT) Notable features: 55 µm pixel pitch and 110 µm pixel pitch (usually 14 mm x 14 mm chip, 128 x 128 pixel grid) Operating modes: fine-pitch, spectroscopic, and charge-summing mode (3 RX) Energy calibration: k. Vp technique, Am 241 radioactive source, XRF of Mo, Pb foils 16

Medipix Unsubtracted Bins Range Bin 1: [T 1 to k. Vp] Bin 2: [T 2 to k. Vp] Bin 3: [T 3 to k. Vp] Bin 4: [T 4 to k. Vp] Kishore Rajendran, “MARS Spectral CT technology for orthopaedic applications, ” Ph. D. thesis, University of Otago, Christchurch, New Zealand, 2015. 17

Medipix Subtracted Bins Range Bin 1: [T 1 to T 2] Bin 2: [T 2 to T 3] Bin 3: [T 3 to T 4] Bin 4: [T 4 to k. Vp] Kishore Rajendran, “MARS Spectral CT technology for orthopaedic applications, ” Ph. D thesis, University of Otago, Christchurch, New Zealand, 2015. 18

MARS Project Hardware & Robotics • Detector characterization • Scanner control system • Detector readout electronics Visualization & Image Processing • Preprocessing techniques • Reconstruction algorithms • Material decomposition methods • 3 D rendering and virtual reality Preclinical research • Vascular imaging • Oncology • Bone and cartilage imaging 19

MARS Project Hardware & Robotics • Detector characterization • Scanner control system • Detector readout electronics Visualization & Image Processing • Preprocessing techniques • Reconstruction algorithms • Material decomposition methods • 3 D rendering and virtual reality Preclinical research • Vascular imaging • Oncology • Bone and cartilage imaging 20

Orthopaedic applications of MARS • Reducing metal artefacts in implant imaging • Quantitative cartilage imaging for osteoarthritis • Characterizing additive manufactured scaffolds for tissue engineering 21

Orthopaedic applications of MARS Reducing beam hardening effects and metal artefacts in spectral CT using Medipix 3 RX 22

X-ray beam hardening 23

CT metal artefacts Image courtesy: Dr Nigel Anderson, Radiology, Christchurch Hospital, New Zealand 24

Cupping effect due to beam hardening Cupping effect 25

Spectral CT approach T 1 T 2 T 3 T 4 26

Test samples • Titanium and cobalt-chromium alloys • Aluminium and stainless-steel Christchurch Regenerative Medicine and Tissue Engineering (CRea. TE) 27

Metal artefact reduction in Ti scaffold CNR = 4. 8, 5. 4, 7. 9 and 8. 1 respectively K. Rajendran et. al, Reducing Beam hardening and metal artefacts in spectral CT using Medipix 3 RX, Journal of Instrumentation, Vol. 9 P 03015, March 2014. 28

Co. Cr + PMMA – Spectral reconstruction 5. 5 mm Energy CNR 50 to 120 ke. V 16. 9 60 to 120 ke. V 17. 6 70 to 120 ke. V 18. 7 80 to 120 ke. V 19. 4 K. Rajendran et. al, Assessing metal artefacts in multi-energy CT , In Preparation 29

Steel phantom 15 to 120 ke. V 35 to 120 ke. V 12. 5 mm 60 to 120 ke. V 80 to 120 ke. V 30 30

3 D visualization – Ti, Co. Cr and ceramic implants Ti screw in PMMA and Co. Cr Ceramic and PMMA

Bony ingrowth in Ti scaffolds imaged using MARS

Orthopaedic applications of MARS Quantitative cartilage imaging for osteoarthritis 33

Priniciple • EPIC – Equilibrium-Partitioned Imaging of Cartilage • Target: Glycosaminoglycans (GAG) – GAG depletion occurs during osteoarthritis (OA) – GAG can be marked using ionic contrast pharmaceuticals – GAG (negatively-charged) can attract/repel ionic contrast • Current methods for imaging GAG in cartilage – micro. CT - pseudo-quantitative – d. GEMRIC (delayed gadolinium enhanced MRI of cartilage) – low resolution 34

Excised tibial plateau K. Rajendran et. al, Quantitative cartilage imaging using spectral CT, in submission to European Radiology 35

Multi-energy reconstructions 6 mm 36

Multi-energy material decomposition 4 mm

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MARS MD vs. Histology MARS material images GAG histology 39

3 D visualization 40

MARS MD vs. Histology MARS [20 -120 ke. V] MARS-MD (Ca + I) Histology 41

Orthopaedic applications of MARS Characterizing 3 D printed biomaterial scaffolds 42

Additive Manufacturing • Tissue-engineered constructs are used in musculoskelatal regenerative medicine • New composite biomaterials including metal alloys, bioceramics, biodegradable polymers are developed for orthopaedic and dental implants • Scaffolds also incorporate drugs/agents to promote healing at implant sites • Characterizing 3 D-printing processes and evaluating the quality of printed structures are currently limited to surface assessment or pseudo-quantitative micro. CT Spectral CT can enable non-destructive evaluation of 3 D printed scaffolds used in tissue-engineering and regenerative medicine 43

Material identification in Bioglass scaffold Spectral image (15 to 50 ke. V) 2 mm Image segmentation using PCA

Outlook • Spectral CT can provide multi-energy data at a single exposure, and has the potential to reduce radiation dose • Challenges – Sensor fabrication – Detector electronics (charge-sharing and pulse pile-up effects) – Better reconstruction techniques • Near-term implementation – Small-animal scanners and spectral micro. CT – Hybrid CT system – Soft-tissue imaging using low-Z sensors (Si, Ga. As) 45

Hybrid spectral CT Alex M. T. Opie, James R. Bennett, Michael Walsh, Kishore Rajendran, Hengyong Yu, Qiong Xu, Anthony Butler, Philip Butler, Guohua Cao, Aaron M. Mohs and Ge Wang, Study of scan protocol for exposure reduction in hybrid spectral micro-CT, Scanning, 2014, 36(4): 444 – 455. 46

Hybrid spectral reconstruction 47

Summary • Spectral CT is enabled using novel photon-counting detectors • Multi-energy data can be simultaneously acquired at a single x-ray exposure, and tissue types and markers can be quantified • Orthopaedic applications of spectral CT – Metal artefact reduction – Quantitative cartilage imaging – Imaging 3 D printed scaffolds • A human scale MARS scanner prototype to be available by 2020 at Otago School of Medicine, Christchurch, New Zealand Further reading: Mike F. Walsh, Raja Aamir, Raj K. Panta, Kishore Rajendran, Nigel G. Anderson, Anthony P. H. Butler, and Phil H. Butler, Spectral molecular CT with photon-counting detectors, In Solid-state radiation detectors: Technology and applications, Editors: Salah Awadalla and Krzysztof Iniewski, CRC Press, 2015. Chapter 9, pp: 195 - 219 48

Acknowledgements 49

CRea. TE group MARS group 50