Dual-contrast micro-CT enables cartilage lesion detection and tissue condition evaluation ex vivo

Miitu K M Honkanen; Ali Mohammadi; Nikae C R Te Moller; Mohammadhossein Ebrahimi; Wujun Xu; Saskia Plomp; Behdad Pouran; Vesa-Pekka Lehto; Harold Brommer; P René van Weeren; Rami K Korhonen; Juha Töyräs; Janne T A Mäkelä

doi:10.1111/evj.13573

Dual-contrast micro-CT enables cartilage lesion detection and tissue condition evaluation ex vivo

Miitu K M Honkanen, Ali Mohammadi, Nikae C R Te Moller, Mohammadhossein Ebrahimi, Wujun Xu, Saskia Plomp, Behdad Pouran, Vesa-Pekka Lehto, Harold Brommer, P René van Weeren, Rami K Korhonen, Juha Töyräs, Janne T A Mäkelä

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

Background: Post-traumatic osteoarthritis is a frequent joint disease in the horse. Currently, equine medicine lacks effective methods to diagnose the severity of chondral defects after an injury. Objectives: To investigate the capability of dual-contrast-enhanced computed tomography (dual-CECT) for detection of chondral lesions and evaluation of the severity of articular cartilage degeneration in the equine carpus ex vivo. Study design: Pre-clinical experimental study. Methods: In nine Shetland ponies, blunt and sharp grooves were randomly created (in vivo) in the cartilage of radiocarpal and middle carpal joints. The contralateral joint served as control. The ponies were subjected to an 8-week exercise protocol and euthanised 39 weeks after surgery. CECT scanning (ex vivo) of the joints was performed using a micro-CT scanner 1 hour after an intra-articular injection of a dual-contrast agent. The dual-contrast agent consisted of ioxaglate (negatively charged, q = −1) and bismuth nanoparticles (BiNPs, q = 0, diameter ≈ 0.2 µm). CECT results were compared to histological cartilage proteoglycan content maps acquired using digital densitometry. Results: BiNPs enabled prolonged visual detection of both groove types as they are too large to diffuse into the cartilage. Furthermore, proportional ioxaglate diffusion inside the tissue allowed differentiation between the lesion and ungrooved articular cartilage (3 mm from the lesion and contralateral joint). The mean ioxaglate partition in the lesion was 19 percentage points higher (P < 0.001) when compared with the contralateral joint. The digital densitometry and the dual-contrast CECT findings showed good subjective visual agreement. Main limitations: Ex vivo study protocol and a low number of investigated joints. Conclusions: The dual-CECT methodology, used in this study for the first time to image whole equine joints, is capable of effective lesion detection and simultaneous evaluation of the condition of the articular cartilage.

Original language	English
Pages (from-to)	315-324
Number of pages	10
Journal	Equine Veterinary Journal
Volume	55
Issue number	2
Early online date	30 Mar 2022
DOIs	https://doi.org/10.1111/evj.13573
Publication status	Published - Mar 2023

Bibliographical note

Publisher Copyright:
© 2022 The Authors. Equine Veterinary Journal published by John Wiley & Sons Ltd on behalf of EVJ Ltd.

Funding

This study was financially supported by the Vilho, Yrjö and Kalle Väisälä Foundation of the Finnish Academy of Science and Letters, the Research Committee of the Kuopio University Hospital Catchment Area for the State Research Funding (project 5041769), the Academy of Finland (projects 307932, 324529, and 314412), the University of Eastern Finland's Doctoral Programme in Science, Technology and Computing (SCITECO), Emil Aaltonen Foundation (Grant 200016), Alfred Kordelin Foundation (Grant 190111), NWO Graduate Programme Grant (022.005.018), and Dutch Arthritis Association grant (LLP‐22). This study was financially supported by the Vilho, Yrjö and Kalle Väisälä Foundation of the Finnish Academy of Science and Letters, the Research Committee of the Kuopio University Hospital Catchment Area for the State Research Funding (project 5041769), the Academy of Finland (projects 307932, 324529, and 314412), the University of Eastern Finland's Doctoral Programme in Science, Technology and Computing (SCITECO), Emil Aaltonen Foundation (Grant 200016), Alfred Kordelin Foundation (Grant 190111), NWO Graduate Programme Grant (022.005.018), and Dutch Arthritis Association grant (LLP-22). The authors would like to acknowledge the Equine Clinic of Utrecht University for providing facilities to conduct this study. Eija Rahunen is acknowledged for preparing the histological sections and Dristi Regmi for helping with the digital densitometry measurements.

Funders	Funder number
Dutch Arthritis Association	LLP‐22
Kuopio University Hospital Catchment Area for the State Research Funding	5041769
Itä-Suomen Yliopisto
Alfred Kordelinin Säätiö	190111
Academy of Finland	324529, 307932, 314412
Suomalainen Tiedeakatemia
Nederlandse Organisatie voor Wetenschappelijk Onderzoek	022.005.018
Kuopion Yliopistollinen Sairaala
Emil Aaltosen Säätiö	200016
Dutch Arthritis Association

Keywords

articular cartilage
bismuth nanoparticles
contrast-enhanced computed tomography
horse
ioxaglate
osteoarthritis

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Equine Veterinary Journal - 2022 - HonkanenFinal published version, 11.6 MBLicence: CC BY

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Honkanen, M. K. M., Mohammadi, A., Te Moller, N. C. R., Ebrahimi, M., Xu, W., Plomp, S., Pouran, B., Lehto, V.-P., Brommer, H., van Weeren, P. R., Korhonen, R. K., Töyräs, J., & Mäkelä, J. T. A. (2023). Dual-contrast micro-CT enables cartilage lesion detection and tissue condition evaluation ex vivo. Equine Veterinary Journal, 55(2), 315-324. https://doi.org/10.1111/evj.13573

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abstract = "Background: Post-traumatic osteoarthritis is a frequent joint disease in the horse. Currently, equine medicine lacks effective methods to diagnose the severity of chondral defects after an injury. Objectives: To investigate the capability of dual-contrast-enhanced computed tomography (dual-CECT) for detection of chondral lesions and evaluation of the severity of articular cartilage degeneration in the equine carpus ex vivo. Study design: Pre-clinical experimental study. Methods: In nine Shetland ponies, blunt and sharp grooves were randomly created (in vivo) in the cartilage of radiocarpal and middle carpal joints. The contralateral joint served as control. The ponies were subjected to an 8-week exercise protocol and euthanised 39 weeks after surgery. CECT scanning (ex vivo) of the joints was performed using a micro-CT scanner 1 hour after an intra-articular injection of a dual-contrast agent. The dual-contrast agent consisted of ioxaglate (negatively charged, q = −1) and bismuth nanoparticles (BiNPs, q = 0, diameter ≈ 0.2 µm). CECT results were compared to histological cartilage proteoglycan content maps acquired using digital densitometry. Results: BiNPs enabled prolonged visual detection of both groove types as they are too large to diffuse into the cartilage. Furthermore, proportional ioxaglate diffusion inside the tissue allowed differentiation between the lesion and ungrooved articular cartilage (3 mm from the lesion and contralateral joint). The mean ioxaglate partition in the lesion was 19 percentage points higher (P < 0.001) when compared with the contralateral joint. The digital densitometry and the dual-contrast CECT findings showed good subjective visual agreement. Main limitations: Ex vivo study protocol and a low number of investigated joints. Conclusions: The dual-CECT methodology, used in this study for the first time to image whole equine joints, is capable of effective lesion detection and simultaneous evaluation of the condition of the articular cartilage.",

keywords = "articular cartilage, bismuth nanoparticles, contrast-enhanced computed tomography, horse, ioxaglate, osteoarthritis",

author = "Honkanen, \{Miitu K M\} and Ali Mohammadi and \{Te Moller\}, \{Nikae C R\} and Mohammadhossein Ebrahimi and Wujun Xu and Saskia Plomp and Behdad Pouran and Vesa-Pekka Lehto and Harold Brommer and \{van Weeren\}, \{P Ren{\'e}\} and Korhonen, \{Rami K\} and Juha T{\"o}yr{\"a}s and M{\"a}kel{\"a}, \{Janne T A\}",

note = "Publisher Copyright: {\textcopyright} 2022 The Authors. Equine Veterinary Journal published by John Wiley \& Sons Ltd on behalf of EVJ Ltd.",

year = "2023",

month = mar,

doi = "10.1111/evj.13573",

language = "English",

volume = "55",

pages = "315--324",

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T1 - Dual-contrast micro-CT enables cartilage lesion detection and tissue condition evaluation ex vivo

AU - Honkanen, Miitu K M

AU - Mohammadi, Ali

AU - Te Moller, Nikae C R

AU - Ebrahimi, Mohammadhossein

AU - Xu, Wujun

AU - Plomp, Saskia

AU - Pouran, Behdad

AU - Lehto, Vesa-Pekka

AU - Brommer, Harold

AU - van Weeren, P René

AU - Korhonen, Rami K

AU - Töyräs, Juha

AU - Mäkelä, Janne T A

PY - 2023/3

Y1 - 2023/3

N2 - Background: Post-traumatic osteoarthritis is a frequent joint disease in the horse. Currently, equine medicine lacks effective methods to diagnose the severity of chondral defects after an injury. Objectives: To investigate the capability of dual-contrast-enhanced computed tomography (dual-CECT) for detection of chondral lesions and evaluation of the severity of articular cartilage degeneration in the equine carpus ex vivo. Study design: Pre-clinical experimental study. Methods: In nine Shetland ponies, blunt and sharp grooves were randomly created (in vivo) in the cartilage of radiocarpal and middle carpal joints. The contralateral joint served as control. The ponies were subjected to an 8-week exercise protocol and euthanised 39 weeks after surgery. CECT scanning (ex vivo) of the joints was performed using a micro-CT scanner 1 hour after an intra-articular injection of a dual-contrast agent. The dual-contrast agent consisted of ioxaglate (negatively charged, q = −1) and bismuth nanoparticles (BiNPs, q = 0, diameter ≈ 0.2 µm). CECT results were compared to histological cartilage proteoglycan content maps acquired using digital densitometry. Results: BiNPs enabled prolonged visual detection of both groove types as they are too large to diffuse into the cartilage. Furthermore, proportional ioxaglate diffusion inside the tissue allowed differentiation between the lesion and ungrooved articular cartilage (3 mm from the lesion and contralateral joint). The mean ioxaglate partition in the lesion was 19 percentage points higher (P < 0.001) when compared with the contralateral joint. The digital densitometry and the dual-contrast CECT findings showed good subjective visual agreement. Main limitations: Ex vivo study protocol and a low number of investigated joints. Conclusions: The dual-CECT methodology, used in this study for the first time to image whole equine joints, is capable of effective lesion detection and simultaneous evaluation of the condition of the articular cartilage.

AB - Background: Post-traumatic osteoarthritis is a frequent joint disease in the horse. Currently, equine medicine lacks effective methods to diagnose the severity of chondral defects after an injury. Objectives: To investigate the capability of dual-contrast-enhanced computed tomography (dual-CECT) for detection of chondral lesions and evaluation of the severity of articular cartilage degeneration in the equine carpus ex vivo. Study design: Pre-clinical experimental study. Methods: In nine Shetland ponies, blunt and sharp grooves were randomly created (in vivo) in the cartilage of radiocarpal and middle carpal joints. The contralateral joint served as control. The ponies were subjected to an 8-week exercise protocol and euthanised 39 weeks after surgery. CECT scanning (ex vivo) of the joints was performed using a micro-CT scanner 1 hour after an intra-articular injection of a dual-contrast agent. The dual-contrast agent consisted of ioxaglate (negatively charged, q = −1) and bismuth nanoparticles (BiNPs, q = 0, diameter ≈ 0.2 µm). CECT results were compared to histological cartilage proteoglycan content maps acquired using digital densitometry. Results: BiNPs enabled prolonged visual detection of both groove types as they are too large to diffuse into the cartilage. Furthermore, proportional ioxaglate diffusion inside the tissue allowed differentiation between the lesion and ungrooved articular cartilage (3 mm from the lesion and contralateral joint). The mean ioxaglate partition in the lesion was 19 percentage points higher (P < 0.001) when compared with the contralateral joint. The digital densitometry and the dual-contrast CECT findings showed good subjective visual agreement. Main limitations: Ex vivo study protocol and a low number of investigated joints. Conclusions: The dual-CECT methodology, used in this study for the first time to image whole equine joints, is capable of effective lesion detection and simultaneous evaluation of the condition of the articular cartilage.

KW - articular cartilage

KW - bismuth nanoparticles

KW - contrast-enhanced computed tomography

KW - horse

KW - ioxaglate

KW - osteoarthritis

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SN - 2042-3306

VL - 55

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JO - Equine Veterinary Journal

JF - Equine Veterinary Journal

IS - 2

ER -

Dual-contrast micro-CT enables cartilage lesion detection and tissue condition evaluation ex vivo

Abstract

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Keywords

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