Infrared Spectroscopy Can Differentiate Between Cartilage Injury Models: Implication for Assessment of Cartilage Integrity.

In order to improve the ability of clinical diagnosis to differentiate articular cartilage (AC) injury of different origins, this study explores the sensitivity of mid-infrared (MIR) spectroscopy for detecting structural, compositional, and functional changes in AC resulting from two injury types. Three grooves (two in parallel in the palmar-dorsal direction and one in the mediolateral direction) were made via arthrotomy in the AC of the radial facet of the third carpal bone (middle carpal joint) and of the intermediate carpal bone (the radiocarpal joint) of nine healthy adult female Shetland ponies (age = 6.8 ± 2.6 years; range 4-13 years) using blunt and sharp tools. The defects were randomly assigned to each of the two joints. Ponies underwent a 3-week box rest followed by 8 weeks of treadmill training and 26 weeks of free pasture exercise before being euthanized for osteochondral sample collection. The osteochondral samples underwent biomechanical indentation testing, followed by MIR spectroscopic assessment. Digital densitometry was conducted afterward to estimate the tissue's proteoglycan (PG) content. Subsequently, machine learning models were developed to classify the samples to estimate their biomechanical properties and PG content based on the MIR spectra according to injury type. Results show that MIR is able to discriminate healthy from injured AC (91%) and between injury types (88%). The method can also estimate AC properties with relatively low error (thickness = 12.7% mm, equilibrium modulus = 10.7% MPa, instantaneous modulus = 11.8% MPa). These findings demonstrate the potential of MIR spectroscopy as a tool for assessment of AC integrity changes that result from injury.

Assessment of Ligament Viscoelastic Properties Using Raman Spectroscopy.

Injuries to the ligaments of the knee commonly impact vulnerable and physically active individuals. These injuries can lead to the development of degenerative diseases such as post-traumatic osteoarthritis (PTOA). Non-invasive optical modalities, such as infrared and Raman spectroscopy, provide means for quantitative evaluation of knee joint tissues and have been proposed as potential quantitative diagnostic tools for arthroscopy. In this study, we evaluate Raman spectroscopy as a viable tool for estimating functional properties of collateral ligaments. Artificial trauma was induced by anterior cruciate ligament transection (ACLT) in the left or right knee joint of skeletally mature New Zealand rabbits. The corresponding contralateral (CL) samples were extracted from healthy unoperated joints along with a separate group of control (CNTRL) animals. The rabbits were sacrificed at 8 weeks after ACLT. The ligaments were then harvested and measured using Raman spectroscopy. A uniaxial tensile stress-relaxation testing protocol was adopted for determining several biomechanical properties of the samples. Partial least squares (PLS) regression models were then employed to correlate the spectral data with the biomechanical properties. Results show that the capacity of Raman spectroscopy for estimating the biomechanical properties of the ligament samples varies depending on the target property, with prediction error ranging from 15.78% for tissue cross-sectional area to 30.39% for stiffness. The hysteresis under cyclic loading at 2 Hz (RMSE = 6.22%, Normalized RMSE = 22.24%) can be accurately estimated from the Raman data which describes the viscous damping properties of the tissue. We conclude that Raman spectroscopy has the potential for non-destructively estimating ligament biomechanical properties in health and disease, thus enhancing the diagnostic value of optical arthroscopic evaluations of ligament integrity.

Assessment of obstructive sleep apnea-related sleep fragmentation utilizing deep learning-based sleep staging from photoplethysmography.

STUDY OBJECTIVES: To assess the relationship between obstructive sleep apnea (OSA) severity and sleep fragmentation, accurate differentiation between sleep and wakefulness is needed. Sleep staging is usually performed manually using electroencephalography (EEG). This is time-consuming due to complexity of EEG setup and the amount of work in manual scoring. In this study, we aimed to develop an automated deep learning-based solution to assess OSA-related sleep fragmentation based on photoplethysmography (PPG) signal. METHODS: A combination of convolutional and recurrent neural networks was used for PPG-based sleep staging. The models were trained using two large clinical datasets from Israel (n = 2149) and Australia (n = 877) and tested separately on three-class (wake/NREM/REM), four-class (wake/N1 + N2/N3/REM), and five-class (wake/N1/N2/N3/REM) classification. The relationship between OSA severity categories and sleep fragmentation was assessed using survival analysis of mean continuous sleep. Overlapping PPG epochs were applied to artificially obtain denser hypnograms for better identification of fragmented sleep. RESULTS: Automatic PPG-based sleep staging achieved an accuracy of 83.3% on three-class, 74.1% on four-class, and 68.7% on five-class models. The hazard ratios for decreased mean continuous sleep compared to the non-OSA group obtained with Cox proportional hazards models with 5-s epoch-to-epoch intervals were 1.70, 3.30, and 8.11 for mild, moderate, and severe OSA, respectively. With EEG-based hypnograms scored manually with conventional 30-s epoch-to-epoch intervals, the corresponding hazard ratios were 1.18, 1.78, and 2.90. CONCLUSIONS: PPG-based automatic sleep staging can be used to differentiate between OSA severity categories based on sleep continuity. The differences between the OSA severity categories become more apparent when a shorter epoch-to-epoch interval is used.

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.

Detailed Assessment of Sleep Architecture With Deep Learning and Shorter Epoch-to-Epoch Duration Reveals Sleep Fragmentation of Patients With Obstructive Sleep Apnea.

Traditional sleep staging with non-overlapping 30-second epochs overlooks multiple sleep-wake transitions. We aimed to overcome this by analyzing the sleep architecture in more detail with deep learning methods and hypothesized that the traditional sleep staging underestimates the sleep fragmentation of obstructive sleep apnea (OSA) patients. To test this hypothesis, we applied deep learning-based sleep staging to identify sleep stages with the traditional approach and by using overlapping 30-second epochs with 15-, 5-, 1-, or 0.5-second epoch-to-epoch duration. A dataset of 446 patients referred for polysomnography due to OSA suspicion was used to assess differences in the sleep architecture between OSA severity groups. The amount of wakefulness increased while REM and N3 decreased in severe OSA with shorter epoch-to-epoch duration. In other OSA severity groups, the amount of wake and N1 decreased while N3 increased. With the traditional 30-second epoch-to-epoch duration, only small differences in sleep continuity were observed between the OSA severity groups. With 1-second epoch-to-epoch duration, the hazard ratio illustrating the risk of fragmented sleep was 1.14 (p = 0.39) for mild OSA, 1.59 (p < 0.01) for moderate OSA, and 4.13 (p < 0.01) for severe OSA. With shorter epoch-to-epoch durations, total sleep time and sleep efficiency increased in the non-OSA group and decreased in severe OSA. In conclusion, more detailed sleep analysis emphasizes the highly fragmented sleep architecture in severe OSA patients which can be underestimated with traditional sleep staging. The results highlight the need for a more detailed analysis of sleep architecture when assessing sleep disorders.

Synchrotron MicroCT Reveals the Potential of the Dual Contrast Technique for Quantitative Assessment of Human Articular Cartilage Composition.

Dual contrast micro computed tomography (CT) shows potential for detecting articular cartilage degeneration. However, the performance of conventional CT systems is limited by beam hardening, low image resolution (full-body CT), and long acquisition times (conventional microCT). Therefore, to reveal the full potential of the dual contrast technique for imaging cartilage composition we employ the technique using synchrotron microCT. We hypothesize that the above-mentioned limitations are overcome with synchrotron microCT utilizing monochromatic X-ray beam and fast image acquisition. Human osteochondral samples (n = 41, four cadavers) were immersed in a contrast agent solution containing two agents (cationic CA4+ and non-ionic gadoteridol) and imaged with synchrotron microCT at an early diffusion time point (2 h) and at diffusion equilibrium (72 h) using two monochromatic X-ray energies (32 and 34 keV). The dual contrast technique enabled simultaneous determination of CA4+ (i.e., proteoglycan content) and gadoteridol (i.e., water content) partitions within cartilage. Cartilage proteoglycan content and biomechanical properties correlated significantly (0.327 < r < 0.736, p < 0.05) with CA4+ partition in superficial and middle zones at both diffusion time points. Normalization of the CA4+ partition with gadoteridol partition within the cartilage significantly (p < 0.05) improved the detection sensitivity for human osteoarthritic cartilage proteoglycan content, biomechanical properties, and overall condition (Mankin, Osteoarthritis Research Society International, and International Cartilage Repair Society grading systems). The dual energy technique combined with the dual contrast agent enables assessment of human articular cartilage proteoglycan content and biomechanical properties based on CA4+ partition determined using synchrotron microCT. Additionally, the dual contrast technique is not limited by the beam hardening artifact of conventional CT systems. © 2019 The Authors. Journal of Orthopaedic Research® published by Wiley Periodicals, Inc. on behalf of Orthopaedic Research Society. J Orthop Res 38:563-573, 2020.

Ultrasound Assessment of Human Meniscus.

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 < 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.

Porosity predicted from ultrasound backscatter using multivariate analysis can improve accuracy of cortical bone thickness assessment.

A rapidly growing area of interest in quantitative ultrasound assessment of bone is to determine cortical bone porosity from ultrasound backscatter. Current backscatter analyses are based on numerical simulations, while there are no published reports of successful experimental measurements. In this study, multivariate analysis is applied to ultrasound reflections and backscatter to predict cortical bone porosity. The porosity is then applied to estimate cortical bone radial speed of sound (SOS) and thickness using ultrasound backscatter signals obtained at 2.25 and 5 MHz center frequencies from cortical bone samples (n = 43) extracted from femoral diaphyses. The study shows that the partial least squares regression technique could be employed to successfully predict (R2 = 0.71-0.73) cortical porosity. It is found that this multivariate approach can reduce uncertainty in pulse-echo assessment of cortical bone thickness from 0.220 to 0.045 mm when porosity based radial SOS was applied, instead of a constant value from literature. Upon further validation, accurate estimation of cortical bone porosity and thickness may be applied as a financially viable option for fracture risk assessment of individuals.

Assessment of the suitability of using a forehead EEG electrode set and chin EMG electrodes for sleep staging in polysomnography.

Recently, a number of portable devices designed for full polysomnography at home have appeared. However, current scalp electrodes used for electroencephalograms are not practical for patient self-application. The aim of this study was to evaluate the suitability of recently introduced forehead electroencephalogram electrode set and supplementary chin electromyogram electrodes for sleep staging. From 31 subjects (10 male, 21 female; age 31.3 ± 11.8 years), sleep was recorded simultaneously with a forehead electroencephalogram electrode set and with a standard polysomnography setup consisting of six recommended electroencephalogram channels, two electrooculogram channels and chin electromyogram. Thereafter, two experienced specialists scored each recording twice, based on either standard polysomnography or forehead recordings. Sleep variables recorded with the forehead electroencephalogram electrode set and separate chin electromyogram electrodes were highly consistent with those obtained with the standard polysomnography. There were no statistically significant differences in total sleep time, sleep efficiency or sleep latencies. However, compared with the standard polysomnography, there was a significant increase in the amount of stage N1 and N2, and a significant reduction in stage N3 and rapid eye movement sleep. Overall, epoch-by-epoch agreement between the methods was 79.5%. Inter-scorer agreement for the forehead electroencephalogram was only slightly lower than that for standard polysomnography (76.1% versus 83.2%). Forehead electroencephalogram electrode set as supplemented with chin electromyogram electrodes may serve as a reliable and simple solution for recording total sleep time, and may be adequate for measuring sleep architecture. Because this electrode concept is well suited for patient's self-application, it may offer a significant advancement in home polysomnography.

Arthroscopic Ultrasound Assessment of Articular Cartilage in the Human Knee Joint: A Potential Diagnostic Method.

OBJECTIVE: We tested whether an intra-articular ultrasound (IAUS) method could be used to evaluate cartilage status arthroscopically in human knee joints in vivo. DESIGN: Seven patients undergoing arthroscopic surgery of the knee were enrolled in this study. An ultrasonic examination was conducted using the same portals as in the arthroscopic surgery. A high-frequency (40-MHz) ultrasound transducer (diameter = 1 mm) was directed to the desired location on the articular surface under arthroscopic control. In addition to ultrasound data, an IAUS video and optical video through the arthroscope were recorded. Classification of cartilage injuries according to International Cartilage Repair Society, as conducted by the orthopedic surgeon, provided reference data for comparison with the IAUS. RESULTS: The IAUS method was successful in imaging different characteristics of the articular surfaces (e.g., intact surface, surface fibrillation, and lesions of varying depth). In some cases, also the subchondral bone and abnormal internal cartilage structure were visible in the IAUS images. Specifically, using the IAUS, a local cartilage lesion of 1 patient was found to be deeper than estimated arthroscopically. CONCLUSIONS: The IAUS method provided a novel arthroscopic method for quantitative imaging of articular cartilage lesions. The IAUS provided quantitative information about the cartilage integrity and thickness, which are not available in conventional arthroscopy. The present equipment is already approved by the Food and Drug Administration for intravascular use and might be transferred to intra-articular use. The invasiveness of the IAUS method might restrict its wider clinical use but combined with arthroscopy, ultrasonic assessment may enlarge the diagnostic potential of arthroscopic surgery.

Evaluation of a novel ambulatory device for screening of sleep apnea.

The gold standard for diagnosis of obstructive sleep apnea (OSA) is the sleep laboratory polysomnography, which is technically demanding, labor-intensive, and time-consuming. Thus, screening of large undiagnosed population for OSA may be cost efficient only by means of ambulatory devices suitable for home recordings. The aim of our study was to evaluate the diagnostic and technical reliability of a novel ambulatory device (APV2, Remote Analysis Oy) introduced for sleep apnea diagnostics. APV2 records breathing movements, nasal and oral air flow, position, snore, blood oxygen saturation, and heart rate. The evaluation was done by comparing 10 simultaneous polygraphic recordings with APV2 and with commonly used clinical reference instrumentation (Embla, Embla Co.) at a sleep laboratory. Furthermore, the technical reliability of measurements was evaluated by analyzing the fraction of clinical APV2 and Embletta (Embla Co.) home recordings (n = 149 and n = 169, respectively) that were technically of diagnostically unacceptable quality. Similar diagnostic sensitivity in detecting OSA was found with the APV2 compared to the simultaneous reference recording with the Embla. Apnea-hypopnea indices and oxygen desaturation indices, recorded with APV2 and Embla, were closely correlated (r = 0.996-0.997, p < 0.0001). The quality of 90.0% of home recordings with APV2 was technically perfect and 96.0% of recordings were of diagnostically acceptable quality. As a comparison, the clinical evaluation of a widely used ambulatory polygraphy device (Embletta) showed that 77.2% of home recordings were technically perfect and 80.8% of recordings were diagnostically acceptable. In conclusion, the novel device was found clinically applicable, technically reliable, and sensitive for the diagnostics of OSA.

Ultrasonic assessment of cortical bone thickness in vitro and in vivo.

In osteoporosis, total bone mass decreases and the thickness of the cortical layer diminishes in the shafts of the long bones. In this study, a simple ultrasonic in vivo method for determining the thickness of the cortical bone layer was applied, and the suitability of two different signal analysis techniques, i.e., envelope and cepstral methods, for measuring cortical thickness was compared. The values of cortical thickness, as determined with both techniques, showed high linear correlations (r > or = 0.95) with the thickness values obtained from in vitro measurements with a caliper or in vivo measurements by peripheral quantitative CT (pQCT). No systematic errors that could be related to the cortical thickness were found. The in vivo accuracy of the measurements was 6.6% and 7.0% for the envelope and cepstral methods, respectively. Further, the in vivo precision for the envelope and cepstral methods was 0.26 mm and 0.28 mm, respectively. Although the results are similar for both of the techniques, the simplicity of the envelope method makes it more attractive for clinical applications. In conclusion, a simple ultrasound measurement provides an accurate estimate of the cortical bone thickness. The techniques investigated may have clinical potential for osteoporosis screening and therefore warrant more extensive clinical investigations with healthy and osteoporotic individuals.

Spatial assessment of articular cartilage proteoglycans with Gd-DTPA-enhanced T1 imaging.

In Gd-DTPA-enhanced T(1) imaging of articular cartilage, the MRI contrast agent with two negative charges is understood to accumulate in tissue inversely to the negative charge of cartilage glycosaminoglycans (GAGs) of proteoglycans (PGs), and this leads to a decrease in the T(1) relaxation time of tissue relative to the charge in tissue. By assuming a constant relaxivity for Gd-DTPA in cartilage, it has further been hypothesized that the contrast agent concentration in tissue could be estimated from consecutive T(1) measurements in the absence or presence of the contrast agent. The spatial sensitivity of the technique was examined at 9.4 T in normal and PG-depleted bovine patellar cartilage samples. As a reference, spatial PG concentration was assessed with digital densitometry from safranin O-stained cartilage sections. An excellent linear correlation between spatial optical density (OD) of stained GAGs and T(1) with Gd-DTPA was observed in the control and chondroitinase ABC-treated cartilage specimens, and the MR parameter accounted for approximately 80% of the variations in GAG concentration within samples. Further, the MR-resolved Gd-DTPA concentration proved to be an even better estimate for PGs, with an improved correlation. However, the linear relation between MR parameters and PG concentration did not apply in the deep tissue, where MR measurements overestimated the PG content. While the absolute [Gd-DTPA] determination may be prone to error due to uncertainty of relaxivity in cartilage, or to other contributing factors such as variations in tissue permeability, the experimental evidence highlights the sensitivity of this technique to reflect spatial changes in cartilage PG concentration in normal and degenerated tissue.