Triple Contrast CT Method Enables Simultaneous Evaluation of Articular Cartilage Composition and Segmentation

Early degenerative changes of articular cartilage are detected using contrast-enhanced computed tomography (CT) with a cationic contrast agent (CA). However, cationic CA diffusion into degenerated cartilage decreases with proteoglycan depletion and increases with elevated water content, thus hampering tissue evaluation at early diffusion time points. Furthermore, the contrast at synovial fluid-cartilage interface diminishes as a function of diffusion time hindering accurate cartilage segmentation. For the first time, we employ quantitative dual-energy CT (QDECT) imaging utilizing a mixture of three CAs (cationic CA4+ and non-ionic gadoteridol which are sensitive to proteoglycan and water contents, respectively, and bismuth nanoparticles which highlight the cartilage surface) to simultaneously segment the articulating surfaces and determine of the cartilage condition. Intact healthy, proteoglycan-depleted, and mechanically injured bovine cartilage samples (n = 27) were halved and imaged with synchrotron microCT 2-h post immersion in triple CA or in dual CA (CA4+ and gadoteridol). CA4+ and gadoteridol partitions were determined using QDECT, and pairwise evaluation of these partitions was conducted for samples immersed in dual and triple CAs. In conclusion, the triple CA method is sensitive to proteoglycan depletion while maintaining sufficient contrast at the articular surface to enable detection of cartilage lesions caused by mechanical impact

Quantitative dual contrast photon-counting computed tomography for assessment of articular cartilage health

Photon-counting detector computed tomography (PCD-CT) is a modern spectral imaging technique utilizing photon-counting detectors (PCDs). PCDs detect individual photons and classify them into fixed energy bins, thus enabling energy selective imaging, contrary to energy integrating detectors that detects and sums the total energy from all photons during acquisition. The structure and composition of the articular cartilage cannot be detected with native CT imaging but can be assessed using contrast-enhancement. Spectral imaging allows simultaneous decomposition of multiple contrast agents, which can be used to target and highlight discrete cartilage properties. Here we report, for the first time, the use of PCD-CT to quantify a cationic iodinated CA4+(targeting proteoglycans) and a non-ionic gadolinium-based gadoteridol (reflecting water content) contrast agents inside human osteochondral tissue (n=53). We performed PCD-CT scanning at diffusion equilibrium and compared the results against reference data of biomechanical and optical density measurements, and Mankin scoring. PCD-CT enables simultaneous quantification of the two contrast agent concentrations inside cartilage and the results correlate with the structural and functional reference parameters. With improved soft tissue contrast and assessment of proteoglycan and water contents, PCD-CT with the dual contrast agent method is of potential use for the detection and monitoring of osteoarthritis.Peer reviewe

Imaging of proteoglycan and water contents in human articular cartilage with full-body CT using dual contrast technique

Assessment of cartilage composition via tomographic imaging is critical after cartilage injury to prevent post-traumatic osteoarthritis. Diffusion of cationic contrast agents in cartilage is affected by proteoglycan loss and elevated water content. These changes have opposite effects on diffusion and, thereby, reduce the diagnostic accuracy of cationic agents. Here, we apply, for the first time, a clinical full-body CT for dual contrast imaging of articular cartilage. We hypothesize that full-body CT can simultaneously determine the diffusion and partitioning of cationic and non-ionic contrast agents and that normalization of the cationic agent partition with that of the non-ionic agent minimizes the effect of water content and tissue permeability, especially at early diffusion time points. Cylindrical (d = 8 mm) human osteochondral samples (n = 45; four cadavers) of a variable degenerative state were immersed in a mixture of cationic iodinated CA4+ and non-charged gadoteridol contrast agents and imaged with a full-body CT scanner at various time points. Determination of contrast agents’ distributions within cartilage was possible at all phases of diffusion. At early time points, gadoteridol, and CA4+ distributed throughout cartilage with lower concentrations in the deep cartilage. At ≥24 h, the gadoteridol concentration remained nearly constant, while the CA4+ concentration increased toward deep cartilage. Normalization of the CA4+ partition with that of gadoteridol significantly (p < 0.05) enhanced correlation with proteoglycan content and Mankin score at the early time points. To conclude, the dual contrast technique was found advantageous over single contrast imaging enabling more sensitive diagnosis of cartilage degeneration

Method for segmentation of knee articular cartilages based on contrast-enhanced CT images

Segmentation of contrast-enhanced computed tomography (CECT) images enables quantitative evaluation of morphology of articular cartilage as well as the significance of the lesions. Unfortunately, automatic segmentation methods for CECT images are currently lacking. Here, we introduce a semiautomated technique to segment articular cartilage from in vivo CECT images of human knee. The segmented cartilage geometries of nine knee joints, imaged using a clinical CT-scanner with an intra-articular contrast agent, were compared with manual segmentations from CT and magnetic resonance (MR) images. The Dice similarity coefficients (DSCs) between semiautomatic and manual CT segmentations were 0.79–0.83 and sensitivity and specificity values were also high (0.76–0.86). When comparing semiautomatic and manual CT segmentations, mean cartilage thicknesses agreed well (intraclass correlation coefficient = 0.85–0.93); the difference in thickness (mean ± SD) was 0.27 ± 0.03\ua0mm. Differences in DSC, when MR segmentations were compared with manual and semiautomated CT segmentations, were statistically insignificant.\ua0Similarly, differences in volume were not statistically significant between manual and semiautomatic CT segmentations. Semiautomation decreased the segmentation time from 450 ± 190 to 42 ± 10\ua0min per joint. The results reveal that the proposed technique is fast and reliable for segmentation of cartilage. Importantly, this is the first study presenting semiautomated segmentation of cartilage from CECT images of human knee joint with minimal user interaction

Simultaneous quantitation of cationic and non-ionic contrast agents in articular cartilage using synchrotron MicroCT imaging

Early diagnosis of acute cartilage injuries enables monitoring of disease progression and improved treatment option planning to prevent post-traumatic osteoarthritis. In contrast-enhanced computed tomography (CECT), the changes in cationic agent diffusion within the tissue reflect cartilage degeneration. The diffusion in degenerated cartilage depends on proteoglycan (PG) content and water content, but each having an opposite effect on diffusion, thus compromising the diagnostic sensitivity. To overcome this limitation, we propose the simultaneous imaging of cationic (sensitive to PG and water contents) and non-ionic (sensitive to water content) agents. In this study, quantitative dual-energy CT (QDECT) imaging of two agents is reported for the first time at clinically feasible imaging time points. Furthermore, this is the first time synchrotron microCT with monochromatic X-rays is employed in cartilage CECT. Imaging was conducted at 1 and 2 h post contrast agent immersion. Intact, PG-depleted, and mechanically injured + PG-depleted cartilage samples (n = 33) were imaged in a mixture of cationic (iodine-based CA4+) and non-ionic (gadolinium-based gadoteridol) agents. Concurrent evaluation of CA4+ and gadoteridol partitions in cartilage is accomplished using QDECT. Subsequent normalization of the CA4+ partition with that of the gadoteridol affords CA4+ attenuations that significantly correlate with PG content – a key marker of OA

Triple Contrast CT Method Enables Simultaneous Evaluation of Articular Cartilage Composition and Segmentation

Early degenerative changes of articular cartilage are detected using contrast-enhanced computed tomography (CT) with a cationic contrast agent (CA). However, cationic CA diffusion into degenerated cartilage decreases with proteoglycan depletion and increases with elevated water content, thus hampering tissue evaluation at early diffusion time points. Furthermore, the contrast at synovial fluid-cartilage interface diminishes as a function of diffusion time hindering accurate cartilage segmentation. For the first time, we employ quantitative dual-energy CT (QDECT) imaging utilizing a mixture of three CAs (cationic CA4+ and non-ionic gadoteridol which are sensitive to proteoglycan and water contents, respectively, and bismuth nanoparticles which highlight the cartilage surface) to simultaneously segment the articulating surfaces and determine of the cartilage condition. Intact healthy, proteoglycan-depleted, and mechanically injured bovine cartilage samples (n = 27) were halved and imaged with synchrotron microCT 2-h post immersion in triple CA or in dual CA (CA4+ and gadoteridol). CA4+ and gadoteridol partitions were determined using QDECT, and pairwise evaluation of these partitions was conducted for samples immersed in dual and triple CAs. In conclusion, the triple CA method is sensitive to proteoglycan depletion while maintaining sufficient contrast at the articular surface to enable detection of cartilage lesions caused by mechanical impact

Optical spectroscopic characterization of human meniscus biomechanical properties

This study investigates the capacity of optical spectroscopy in the visible (VIS) and near-infrared (NIR) spectral ranges for estimating the biomechanical properties of human meniscus. Seventy-two samples obtained from the anterior, central, and posterior locations of the medial and lateral menisci of 12 human cadaver joints were used. The samples were subjected to mechanical indentation, then traditional biomechanical parameters (equilibrium and dynamic moduli) were calculated. In addition, strain-dependent fibril network modulus and permeability strain-dependency coefficient were determined via finite-element modeling. Subsequently, absorption spectra were acquired from each location in the VIS (400 to 750 nm) and NIR (750 to 1100 nm) spectral ranges. Partial least squares regression, combined with spectral preprocessing and transformation, was then used to investigate the relationship between the biomechanical properties and spectral response. The NIR spectral region was observed to be optimal for model development (83.0% Le R2 ≤ 90.8%).e. The NIR spectral region was observed to be optimal for model development (83.0%≤R2≤90.8%). The percentage error of the models are: Eeq (7.1%), E (9.6%), E (8.4%), and M (8.9%). Thus, we conclude that optical spectroscopy in the NIR range is a potential method for rapid and nondestructive evaluation of human meniscus functional integrity and health in real time during arthroscopic surgery

Ultrasound assessment of human meniscus

Abstract The aim of the present study was to evaluate the applicability of ultrasound imaging to quantitative assessment of human meniscus in vitro. Meniscus samples (n = 26) were harvested from 13 knee joints of non-arthritic human cadavers. Subsequently, three locations (anterior, center and posterior) from each meniscus were imaged with two ultrasound transducers (frequencies 9 and 40 MHz), and quantitative ultrasound parameters were determined. Furthermore, partial-least-squares regression analysis was applied for ultrasound signal to determine the relations between ultrasound scattering and meniscus integrity. Significant correlations between measured and predicted meniscus compositions and mechanical properties were obtained (R² = 0.38–0.69, p &lt; 0.05). The relationship between conventional ultrasound parameters and integrity of the meniscus was weaker. To conclude, ultrasound imaging exhibited a potential for evaluation of meniscus integrity. Higher ultrasound frequency combined with multivariate analysis of ultrasound backscattering was found to be the most sensitive for evaluation of meniscus integrity

In Vivo contrast-enhanced cone beam CT provides quantitative information on articular cartilage and subchondral bone

In post-traumatic osteoarthritis, both articular cartilage and subchondral bone undergo characteristic pathological changes. This study investigates potential of delayed cone beam computed tomography arthrography (dCBCTa) to simultaneously detect variations in cartilage and subchondral bone. The knees of patients (n\ua0=\ua017) with suspected joint injuries were imaged using a clinical CBCT scanner at 5 and 45\ua0min after the intra-articular injection of anionic contrast agent (Hexabrix™) with hydroxyapatite phantoms around the knee. Normalized attenuation (i.e., contrast agent partition, an indicator of tissue composition) in cartilage, bone mineral density (BMD) in subchondral bone plate (SBP), subchondral bone and trabecular bone, and thicknesses of SBP and cartilage were determined. Lesions of cartilage were scored using International Cartilage Repair Society (ICRS) grading. Normalized attenuation in the delayed image (t\ua0=\ua045\ua0min) increased along the increase of ICRS grade (p\ua0=\ua00.046). Moreover, BMD was significantly higher in SBPs under damaged cartilage (ICRS\ua0=\ua01–2 or ICRS\ua0≥\ua03; p\ua0=\ua00.047\ua0and p\ua0=\ua00.038, respectively) than in SBP under non-injured tissue (ICRS\ua0=\ua00). For the first time, dCBCTa enabled the detection of articular cartilage injuries and subchondral bone alterations simultaneously in vivo. Significant relations between ICRS grading and both cartilage and bone parameters suggest that dCBCTa has potential for quantitative imaging of the knee joint

Quantitative dual contrast photon-counting computed tomography for assessment of articular cartilage health

Abstract Photon-counting detector computed tomography (PCD-CT) is a modern spectral imaging technique utilizing photon-counting detectors (PCDs). PCDs detect individual photons and classify them into fixed energy bins, thus enabling energy selective imaging, contrary to energy integrating detectors that detects and sums the total energy from all photons during acquisition. The structure and composition of the articular cartilage cannot be detected with native CT imaging but can be assessed using contrast-enhancement. Spectral imaging allows simultaneous decomposition of multiple contrast agents, which can be used to target and highlight discrete cartilage properties. Here we report, for the first time, the use of PCD-CT to quantify a cationic iodinated CA4+ (targeting proteoglycans) and a non-ionic gadolinium-based gadoteridol (reflecting water content) contrast agents inside human osteochondral tissue (n = 53). We performed PCD-CT scanning at diffusion equilibrium and compared the results against reference data of biomechanical and optical density measurements, and Mankin scoring. PCD-CT enables simultaneous quantification of the two contrast agent concentrations inside cartilage and the results correlate with the structural and functional reference parameters. With improved soft tissue contrast and assessment of proteoglycan and water contents, PCD-CT with the dual contrast agent method is of potential use for the detection and monitoring of osteoarthritis