Osteoarthritis (OA) is the most common degenerative joint disease, afflicting ~30 million US adults and currently lacking effective treatment. OA diagnosis with radiography and MRI relies predominantly on biomarkers of late disease, and capability for early detection of OA could enable therapies preventing irreversible cartilage loss. Changes in subchondral bone (SB) architecture and bone mineral density (BMD) have been identified as possible biomarkers of early disease and a target for therapy. However, this potential advance in OA diagnosis and treatment is hampered by the lack of imaging technology that combines the high level of spatial resolution required to characterize trabecular architecture (<0.2 mm) with a high degree of quantitative accuracy enabling reliable BMD measurement and the ability to image large joints in vivo. Dedicated extremity cone-beam CT (CBCT) is a recent advance providing the capability for weight-bearing imaging, reduced dose, and superior spatial resolution (~0.3 mm) compared to conventional CT, as demonstrated in clinical studies using a system developed at our institution. We hypothesize that an advanced system for extremity CBCT utilizing a novel CMOS detector, model-based image reconstruction, and patient-specific scatter correction will provide simultaneous in-vivo assessment of SB architecture, BMD, and joint space morphology for early diagnosis and evaluation of treatment response in OA. The development and clinical translation of the system supporting this hypothesis involve the following Specific Aims: 1) Develop an advanced extremity CBCT configuration for in-vivo assessment of bone health employing a fast, low-noise, high-resolution CMOS detector within a system optimized for OA imaging tasks and compatible with rapid translation to the extremity CBCT clinical prototype; 2) Enhance spatial resolution in CBCT beyond conventional limits with model-based reconstruction incorporating a model of system blur, fiducially-free rigid motion correction, and a volume-of-interest, multi-resolution object representation to yield minimum resolvable detail size of ~0.1 mm to facilitate accurate SB morphometry; 3) Improve quantitative accuracy and soft tissue contrast (e.g., cartilage and tendons) using a patient-specific scatter correction with Monte Carlo calculation accelerated with iterative de-noising (anticipated correction time ~2 min/scan) and by developing a novel, automatic BMD calibration system integrated with the scanner enclosure to yield BMD accuracy better than 3%; and 4) Integrate the systems from Aims 1-3 onto a clinical platform for extremity CBCT and evaluate the system in a clinical pilot study to assess potential diagnostic performance and reproducibility of the SB architecture and BMD measurement. The project will advance the resolution and quantitative accuracy of CBCT translated to pilot studies pertinent to the early detection and staging of OA, with potential application in other areas of bone health e.g. rheumatoid arthritis or osteoporosis. The research is conducted in an academic-industry consortium between Johns Hopkins University and Carestream Health.

Public Health Relevance

Osteoarthritis (OA) is a leading cause of disability that lacks convenient biomarkers for early detection and treatment response. Subchondral bone microstructure is a likely biomarker of early OA and is a target for experimental therapies. The project develops an ultra-high resolution cone-beam CT with spatial resolution and quantitative accuracy sufficient to assess subchondral bone health in-vivo, yielding an innovative technology with major relevance to human health in advancing the studies of OA pathogenesis and treatment.

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Research Project (R01)
Project #
5R01EB018896-04
Application #
9342891
Study Section
Biomedical Imaging Technology Study Section (BMIT)
Program Officer
Zubal, Ihor George
Project Start
2014-09-01
Project End
2019-08-31
Budget Start
2017-09-01
Budget End
2019-08-31
Support Year
4
Fiscal Year
2017
Total Cost
Indirect Cost
Name
Johns Hopkins University
Department
Biomedical Engineering
Type
Schools of Medicine
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21205
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Tilley, Steven; Jacobson, Matthew; Cao, Qian et al. (2018) Penalized-Likelihood Reconstruction With High-Fidelity Measurement Models for High-Resolution Cone-Beam Imaging. IEEE Trans Med Imaging 37:988-999
Cao, Qian; Sisniega, Alejandro; Brehler, Michael et al. (2018) Modeling and evaluation of a high-resolution CMOS detector for cone-beam CT of the extremities. Med Phys 45:114-130
Cao, Q; Brehler, M; Sisniega, A et al. (2017) High-resolution extremity cone-beam CT with a CMOS detector: Task-based optimization of scintillator thickness. Proc SPIE Int Soc Opt Eng 10132:
Dang, Hao; Stayman, J Webster; Sisniega, Alejandro et al. (2017) Multi-resolution statistical image reconstruction for mitigation of truncation effects: application to cone-beam CT of the head. Phys Med Biol 62:539-559
Sisniega, A; Stayman, J W; Yorkston, J et al. (2017) Motion compensation in extremity cone-beam CT using a penalized image sharpness criterion. Phys Med Biol 62:3712-3734
Brehler, M; Thawait, G; Shyr, W et al. (2017) Atlas-based automatic measurements of the morphology of the tibiofemoral joint. Proc SPIE Int Soc Opt Eng 10137:
Tilley, Steven; Siewerdsen, Jeffrey H; Zbijewski, Wojciech et al. (2016) Nonlinear Statistical Reconstruction for Flat-Panel Cone-Beam CT with Blur and Correlated Noise Models. Proc SPIE Int Soc Opt Eng 9783:
Sisniega, A; Stayman, J W; Cao, Q et al. (2016) Image-Based Motion Compensation for High-Resolution Extremities Cone-Beam CT. Proc SPIE Int Soc Opt Eng 9783:
Tilley 2nd, Steven; Zbijewski, Wojciech; Siewerdsen, Jeffrey H et al. (2016) Modeling Shift-Variant X-Ray Focal Spot Blur for High-Resolution Flat-Panel Cone-Beam CT. Conf Proc Int Conf Image Form Xray Comput Tomogr 2016:463-466

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