Laser-irradiating infrared attenuated total reflection spectroscopy of articular cartilage: Potential and challenges for diagnosing osteoarthritis.

Objective: A prototype infrared attenuated total reflection (IR-ATR) laser spectroscopic system designed for in vivo classification of human cartilage tissue according to its histological health status during arthroscopic surgery is presented. Prior to real-world in vivo applications, this so-called osteoarthritis (OA) scanner has been tested at in vitro conditions revealing the challenges associated with complex sample matrices and the accordingly obtained sparse spectral datasets. Methods: In vitro studies on human knee cartilage samples at different contact pressures (i.e., 0.2-0.5 â€‹MPa) allowed recording cartilage degeneration characteristic IR signatures comparable to in vivo conditions with high temporal resolution. Afterwards, the cartilage samples were assessed based on the clinically acknowledged osteoarthritis cartilage histopathology assessment (OARSI) system and correlated with the obtained sparse IR data. Results: Amide and carbohydrate signal behavior was observed to be almost identical between the obtained sparse IR data and previously measured FTIR data used for sparse partial least squares discriminant analysis (SPLSDA) to identify the spectral regions relevant to cartilage condition. Contact pressures between 0.3 and 0.4 â€‹MPa seem to provide the best sparse IR spectra for cylindrical (d â€‹= â€‹3 â€‹mm) probe tips. Conclusion: Laser-irradiating IR-ATR spectroscopy is a promising analytical technique for future arthroscopic applications to differentiate healthy and osteoarthritic cartilage tissue. However, this study also revealed that the flexible connection between the laser-based analyzer and the arthroscopic ATR-probe via IR-transparent fiberoptic cables may affect the robustness of the obtained IR data and requires further improvements.

Machine learning augmented near-infrared spectroscopy: In vivo follow-up of cartilage defects.

OBJECTIVE: To assess the potential of near-infrared spectroscopy (NIRS) for in vivo arthroscopic monitoring of cartilage defects. METHOD: Sharp and blunt cartilage grooves were induced in the radiocarpal and intercarpal joints of Shetland ponies and monitored at baseline (0 weeks) and at three follow-up timepoints (11, 23, and 39 weeks) by measuring near-infrared spectra in vivo at and around the grooves. The animals were sacrificed after 39 weeks and the joints were harvested. Spectra were reacquired ex vivo to ensure reliability of in vivo measurements and for reference analyses. Additionally, cartilage thickness and instantaneous modulus were determined via computed tomography and mechanical testing, respectively. The relationship between the ex vivo spectra and cartilage reference properties was determined using convolutional neural network. RESULTS: In an independent test set, the trained networks yielded significant correlations for cartilage thickness (ρ = 0.473) and instantaneous modulus (ρ = 0.498). These networks were used to predict the reference properties at baseline and at follow-up time points. In the radiocarpal joint, cartilage thickness increased significantly with both groove types after baseline and remained swollen. Additionally, at 39 weeks, a significant difference was observed in cartilage thickness between controls and sharp grooves. For the instantaneous modulus, a significant decrease was observed with both groove types in the radiocarpal joint from baseline to 23 and 39 weeks. CONCLUSION: NIRS combined with machine learning enabled determination of cartilage properties in vivo, thereby providing longitudinal evaluation of post-intervention injury development. Additionally, radiocarpal joints were found more vulnerable to cartilage degeneration after damage than intercarpal joints.

Near-infrared spectroscopy enables quantitative evaluation of human cartilage biomechanical properties during arthroscopy.

OBJECTIVE: To investigate the feasibility of near-infrared (NIR) spectroscopy (NIRS) for evaluation of human articular cartilage biomechanical properties during arthroscopy. DESIGN: A novel arthroscopic NIRS probe designed in our research group was utilized by an experienced orthopedic surgeon to measure NIR spectra from articular cartilage of human cadaver knee joints (ex vivo, n = 18) at several measurement locations during an arthroscopic surgery. Osteochondral samples (n = 265) were extracted from the measurement sites for reference analysis. NIR spectra were remeasured in a controlled laboratory environment (in vitro), after which the corresponding cartilage thickness and biomechanical properties were determined. Hybrid multivariate regression models based on principal component analysis and linear mixed effects modeling (PCA-LME) were utilized to relate cartilage in vitro spectra and biomechanical properties, as well as to account for the spatial dependency. Additionally, a k-nearest neighbors (kNN) classifier was employed to reject outlying ex vivo NIR spectra resulting from a non-optimal probe-cartilage contact. Model performance was evaluated for both in vitro and ex vivo NIR spectra via Spearman's rank correlation (ρ) and the ratio of performance to interquartile range (RPIQ). RESULTS: Regression models accurately predicted cartilage thickness and biomechanical properties from in vitro NIR spectra (Model: 0.77 ≤ ρ ≤ 0.87, 2.03 ≤ RPIQ ≤ 3.0; Validation: 0.74 ≤ ρ ≤ 0.84, 1.87 ≤ RPIQ ≤ 2.90). When predicting cartilage properties from ex vivo NIR spectra (0.33 ≤ ρ ≤ 0.57 and 1.02 ≤ RPIQ ≤ 2.14), a kNN classifier enhanced the accuracy of predictions (0.52 ≤ ρ ≤ 0.87 and 1.06 ≤ RPIQ ≤ 1.88). CONCLUSION: Arthroscopic NIRS could substantially enhance identification of damaged cartilage by enabling quantitative evaluation of cartilage biomechanical properties. The results demonstrate the capacity of NIRS in clinical applications.

Semi-automated International Cartilage Repair Society scoring of equine articular cartilage lesions in optical coherence tomography images.

BACKGROUND: Arthroscopic optical coherence tomography (OCT) is a promising tool for the detailed evaluation of articular cartilage injuries. However, OCT-based articular cartilage scoring still relies on the operator's visual estimation. OBJECTIVES: To test the hypothesis that semi-automated International Cartilage Repair Society (ICRS) scoring of chondral lesions seen in OCT images could enhance intra- and interobserver agreement of scoring and its accuracy. STUDY DESIGN: Validation study using equine cadaver tissue. METHODS: Osteochondral samples (n = 99) were prepared from 18 equine metacarpophalangeal joints and imaged using OCT. Custom-made software was developed for semi-automated ICRS scoring of cartilage lesions on OCT images. Scoring was performed visually and semi-automatically by five observers, and levels of inter- and intraobserver agreement were calculated. Subsequently, OCT-based scores were compared with ICRS scores based on light microscopy images of the histological sections of matching locations (n = 82). RESULTS: When semi-automated scoring of the OCT images was performed by multiple observers, mean levels of intraobserver and interobserver agreement were higher than those achieved with visual OCT scoring (83% vs. 77% and 74% vs. 33%, respectively). Histology-based scores from matching regions of interest agreed better with visual OCT-based scoring than with semi-automated OCT scoring; however, the accuracy of the software was improved by optimising the threshold combinations used to determine the ICRS score. MAIN LIMITATIONS: Images were obtained from cadavers. CONCLUSIONS: Semi-automated scoring software improved the reproducibility of ICRS scoring of chondral lesions in OCT images and made scoring less observer-dependent. The image analysis and segmentation techniques adopted in this study warrant further optimisation to achieve better accuracy with semi-automated ICRS scoring. In addition, studies on in vivo applications are required.

Multimodality scoring of chondral injuries in the equine fetlock joint ex vivo.

OBJECTIVE: We investigate the potential of a prototype multimodality arthroscope, combining ultrasound, optical coherence tomography (OCT) and arthroscopic indentation device, for assessing cartilage lesions, and compare the reliability of this approach with conventional arthroscopic scoring ex vivo. DESIGN: Areas of interest (AIs, N = 43) were selected from equine fetlock joints (N = 5). Blind-coded AIs were independently scored by two equine surgeons employing International Cartilage Repair Society (ICRS) scoring system via conventional arthroscope and multimodality arthroscope, in which high-frequency ultrasound and OCT catheters were attached to an arthroscopic indentation device. In addition, cartilage stiffness was measured with the indentation device, and lesions in OCT images scored using custom-made automated software. Measurements and scorings were performed twice in two separate rounds. Finally, the scores were compared to histological ICRS scores. RESULTS: OCT and arthroscopic examinations showed the highest average agreements (55.2%) between the scoring by surgeons and histology scores, whereas ultrasound had the lowest (50.6%). Average intraobserver agreements of surgeons and interobserver agreements between rounds were, respectively, for conventional arthroscope (68.6%, 69.8%), ultrasound (68.6%, 68.6%), OCT (65.1%, 61.7%) and automated software (65.1%, 59.3%). CONCLUSIONS: OCT imaging supplemented with the automated software provided the most reliable lesion scoring. However, limited penetration depth of light limits the clinical potential of OCT in assessing human cartilage thickness; thus, the combination of OCT and ultrasound could be optimal for reliable diagnostics. Present findings suggest imaging and quantitatively analyzing the entire articular surface to eliminate surgeon-related variation in the selection of the most severe lesion to be scored.

New method for point-of-care osteoporosis screening and diagnostics.

SUMMARY: Due to the lack of diagnostics in primary health care, over 75% of osteoporotic patients are not diagnosed. A new ultrasound method for primary health care is proposed. Results suggest applicability of ultrasound method for osteoporosis diagnostics at primary health care. INTRODUCTION: We lack effective screening and diagnostics of osteoporosis at primary health care. In this study, a new ultrasound (US) method is proposed for osteoporosis diagnostics. METHODS: A total of 572 Caucasian women (age 20 to 91 years) were examined using pulse-echo US measurements in the tibia and radius. This method provides an estimate of bone mineral density (BMD), i.e. density index (DI). Areal BMD measurements at the femoral neck (BMD(neck)) and total hip (BMD(total)) were determined by using axial dual-energy X-ray absorptiometry (DXA) for women older than 50 years of age (n = 445, age = 68.8 ± 8.5 years). The osteoporosis thresholds for the DI were determined according to the International Society for Clinical Densitometry (ISCD). Finally, the FRAX questionnaire was completed by 425 participants. RESULTS: Osteoporosis was diagnosed in individuals with a T-score -2.5 or less in the total hip or femoral neck (n = 75). By using the ISCD approach for the DI, only 28.7% of the subjects were found to require an additional DXA measurement. Our results suggest that combination of US measurement and FRAX in osteoporosis management pathways would decrease the number of DXA measurements to 16% and the same treatment decisions would be reached at 85.4% sensitivity and 78.5% specificity levels. CONCLUSIONS: The present results demonstrate a significant correlation between the ultrasound and DXA measurements at the proximal femur. The thresholds presented here with the application to current osteoporosis management pathways show promise for the technique to significantly decrease the amount of DXA referrals and increase diagnostic coverage; however, these results need to be confirmed in future studies.

Estimation of articular cartilage properties using multivariate analysis of optical coherence tomography signal.

OBJECTIVE: The aim was to investigate the applicability of multivariate analysis of optical coherence tomography (OCT) information for determining structural integrity, composition and mechanical properties of articular cartilage. DESIGN: Equine osteochondral samples (N = 65) were imaged with OCT, and their total attenuation and backscattering coefficients (µt and µb) were measured. Subsequently, the Mankin score, optical density (OD) describing the fixed charge density, light absorbance in amide I region (Aamide), collagen orientation, permeability, fibril network modulus (Ef) and non-fibrillar matrix modulus (Em) of the samples were determined. Partial least squares (PLS) regression model was calculated to predict tissue properties from the OCT signals of the samples. RESULTS: Significant correlations between the measured and predicted mean collagen orientation (R(2) = 0.75, P < 0.0001), permeability (R(2) = 0.74, P < 0.0001), mean OD (R(2) = 0.73, P < 0.0001), Mankin scores (R(2) = 0.70, P < 0.0001), Em (R(2) = 0.50, P < 0.0001), Ef (R(2) = 0.42, P < 0.0001), and Aamide (R(2) = 0.43, P < 0.0001) were obtained. Significant correlation was also found between µb and Ef (ρ = 0.280, P = 0.03), but not between µt and any of the determined properties of articular cartilage (P > 0.05). CONCLUSION: Multivariate analysis of OCT signal provided good estimates for tissue structure, composition and mechanical properties. This technique may significantly enhance OCT evaluation of articular cartilage integrity, and could be applied, for example, in delineation of degenerated areas around cartilage injuries during arthroscopic repair surgery.

Thermal imaging in screening of joint inflammation and rheumatoid arthritis in children.

Potential of modern thermal imaging for screening and differentiation of joint inflammation has not been assessed in child and juvenile patient populations, typically demanding groups in diagnostics of musculoskeletal disorders. We hypothesize that thermal imaging can detect joint inflammation in patients with juvenile idiopathic arthritis or autoimmune disease with arthritis such as systemic lupus erythematosus. To evaluate the hypothesis, we studied 58 children exhibiting symptoms of joint inflammation. First, the patients' joints were examined along clinical procedure supplemented with ultrasound imaging when deemed necessary by the clinician. Second, thermal images were acquired from patients' knees and ankles. Results of thermal imaging were compared to clinical evaluations in knee and ankle. The temperatures were significantly (pmax = 0.044, pmean < 0.001) higher in inflamed ankle joints, but not in inflamed knee joints. No significant difference was found between the skin surface temperatures of medial and lateral aspects of ankle joints. In knee joints the mean temperatures of medial and lateral aspect differed significantly (p = 0.004). We have demonstrated that thermal imaging may have potential for detecting joint inflammation in ankle joints of children. For knee joints our results are inconclusive and further research is warranted.

Assessment of myocardial perfusion with MRI using a modified dual bolus method.

Quantification of regional myocardial blood flow (rMBF) with first-pass magnetic resonance imaging (FP-MRI) requires two contrast agent injections (dual bolus technique), inducing error in the determined rMBF if the injections differ. We hypothesize that using input and residue curves of the same injection would be more reliable. We aim to introduce and evaluate a novel method to correct the high concentration arterial input function (AIF) for determination of rMBF. Sixteen patients with non-Hodgkin's lymphoma were examined before and after chemotherapy. The input function was solved by correcting initial high concentration AIF using the ratio of low and high contrast AIF areas, normalized by corresponding heart rates (modified dual bolus method). For comparison, the scaled low contrast AIF was used as an input function (dual bolus method). Unidirectional transfer coefficient K(trans) was calculated using both methods. K(trans)-values determined with the dual bolus (0.81 ± 0.32 ml g(-1) min(-1)) and modified dual bolus (0.77 ± 0.42 ml g(-1) min(-1)) methods were in agreement (p = 0.21). Mean K(trans)-values increased from 0.76 ± 0.43 to 0.89 ± 0.55 ml g(-1) min(-1) after chemotherapy (p = 0.17). The modified dual bolus technique agrees with the dual bolus technique (R2 = 0.899) when the low and high contrast injections are similar. However, when this is not the case, the modified dual bolus technique may be more reliable.

Arthroscopic optical coherence tomography provides detailed information on articular cartilage lesions in horses.

Arthroscopy enables direct inspection of the articular surface, but provides no information on deeper cartilage layers. Optical coherence tomography (OCT), based on measurement of reflection and backscattering of light, is a diagnostic technique used in cardiovascular surgery and ophthalmology. It provides cross-sectional images at resolutions comparable to that of low-power microscopy. The aim of this study was to determine if OCT is feasible for advanced clinical assessment of lesions in equine articular cartilage during diagnostic arthroscopy. Diagnostic arthroscopy of 36 metacarpophalangeal joints was carried out ex vivo. Of these, 18 joints with varying degrees of cartilage damage were selected, wherein OCT arthroscopy was conducted using an OCT catheter (diameter 0.9 mm) inserted through standard instrument portals. Five sites of interest, occasionally supplemented with other locations where defects were encountered, were arthroscopically graded according to the International Cartilage Repair Society (ICRS) classification system. The same sites were evaluated qualitatively (ICRS classification and morphological description of the lesions) and quantitatively (measurement of cartilage thickness) on OCT images. OCT provided high resolution images of cartilage enabling determination of cartilage thickness. Comparing ICRS grades determined by both arthroscopy and OCT revealed poor agreement. Furthermore, OCT visualised a spectrum of lesions, including cavitation, fibrillation, superficial and deep clefts, erosion, ulceration and fragmentation. In addition, with OCT the arthroscopically inaccessible area between the dorsal MC3 and P1 was reachable in some cases. Arthroscopically-guided OCT provided more detailed and quantitative information on the morphology of articular cartilage lesions than conventional arthroscopy. OCT could therefore improve the diagnostic value of arthroscopy in equine orthopaedic surgery.

Arthroscopic ultrasound technique for simultaneous quantitative assessment of articular cartilage and subchondral bone: an in vitro and in vivo feasibility study.

Traditional arthroscopic examination is subjective and poorly reproducible. Recently, we introduced an arthroscopic ultrasound method for quantitative diagnostics of cartilage lesions. Here we describe our investigation of the feasibility of ultrasound arthroscopy for simultaneous measurements of articular cartilage and subchondral bone. Human osteochondral samples (n = 13) were imaged using a clinical 9-MHz ultrasound system. Ultrasound reflection coefficients (R, IRC), the ultrasound roughness index (URI) and the apparent integrated backscattering coefficient (AIB) were determined for both tissues. Mechanical testing, histologic analyses and micro-scale computed tomography imaging were the reference methods. Ultrasound arthroscopies were conducted on two patients. The ultrasound reflection coefficient correlated with the Mankin score and Young's modulus of cartilage (|r| > 0.56, p < 0.05). Ultrasound parameters (R, IRC, AIB) for subchondral bone correlated with the bone surface/volume ratio (|r| > 0.70, p < 0.05) and trabecular thickness (|r| > 0.59, p < 0.05). Furthermore, R and subchondral bone mineral density were significantly correlated (|r| > 0.65, p < 0.05). Arthroscopic ultrasound examination provided diagnostically valuable information on cartilage and subchondral bone in vivo.

In vivo comparison of delayed gadolinium-enhanced MRI of cartilage and delayed quantitative CT arthrography in imaging of articular cartilage.

OBJECTIVE: To compare delayed gadolinium-enhanced magnetic resonance imaging (MRI) of cartilage (dGEMRIC) and delayed quantitative computed tomography (CT) arthrography (dQCTA) to each other, and their association to arthroscopy. Additionally, the relationship between dGEMRIC with intravenous (dGEMRIC(IV)) and intra-articular contrast agent administration (dGEMRIC(IA)) was determined. DESIGN: Eleven patients with knee pain were scanned at 3 T MRI and 64-slice CT before arthroscopy. dQCTA was performed at 5 and 45 min after intra-articular injection of ioxaglate. Both dGEMRIC(IV) and dGEMRIC(IA) were performed at 90 min after gadopentetate injection. dGEMRIC indices and change in relaxation rates (ΔR(1)) were separately calculated for dGEMRIC(IV) and dGEMRIC(IA). dGEMRIC and dQCTA parameters were calculated for predetermined sites at the knee joint that were International Cartilage Repair Society (ICRS) graded in arthroscopy. RESULTS: dQCTA normalized with the contrast agent concentration in synovial fluid (SF) and dGEMRIC(IV) correlated significantly, whereas dGEMRIC(IA) correlated with the normalized dQCTA only when dGEMRIC(IA) was also normalized with the contrast agent concentration in SF. Correlation was strongest between normalized dQCTA at 45 min and ΔR(1,IV) (r(s) = 0.72 [95% CI 0.56-0.83], n = 49, P < 0.01) and ΔR(1,IA) normalized with ΔR(1) in SF (r(s) = 0.70 [0.53-0.82], n = 52, P < 0.01). Neither dGEMRIC nor dQCTA correlated with arthroscopic grading. dGEMRIC(IV) and non-normalized dGEMRIC(IA) were not related while ΔR(1,IV) correlated with normalized ΔR(1,IA) (r(s) = 0.52 [0.28-0.70], n = 50, P < 0.01). CONCLUSIONS: This study suggests that dQCTA is in best agreement with dGEMRIC(IV) at 45 min after CT contrast agent injection. dQCTA and dGEMRIC were not related to arthroscopy, probably because the remaining cartilage is analysed in dGEMRIC and dQCTA, whereas in arthroscopy the absence of cartilage defines the grading. The findings indicate the importance to take into account the contrast agent concentration in SF in dQCTA and dGEMRIC(IA).

Mortality in middle-aged men with obstructive sleep apnea in Finland.

INTRODUCTION: Obstructive sleep apnea (OSA) has been associated with an elevated rate of cardiovascular mortality. However, this issue has not been investigated in patients with elevated proneness to cardiovascular diseases. Our hypothesis was that OSA would have an especially adverse effect on the risk of cardiovascular mortality in Finnish individuals exhibiting elevated proneness for coronary heart diseases. METHODS: Ambulatory polygraphic recordings from 405 men having suspected OSA were retrospectively analyzed. The patients were categorized regarding sleep disordered breathing into a normal group (apnea hypopnea index (AHI) < 5, n = 104), mild OSA group (5 ≤ AHI < 15, n = 100), and moderate to severe OSA group (AHI ≥ 15, n = 201). In addition, basic anthropometric and health data were collected. In patients who died during the follow-up period (at least 12 years and 10 months), the primary and secondary causes of death were recorded. RESULTS: After adjustment for age, BMI, and smoking, the patients with moderate to severe OSA suffered significantly (p < 0.05) higher mortality (hazard ratio 3.13) than their counterparts with normal recordings. The overall mortality in the moderate to severe OSA group was 26.4 %, while in the normal group it was 9.7 %. Hazard ratio for cardiovascular mortality was 4.04 in the moderate to severe OSA and 1.87 in the mild OSA group. CONCLUSIONS: OSA seems to have an especially adverse effect on the cardiovascular mortality of patients with an elevated genetic susceptibility to coronary heart diseases. When considering that all our patients had possibility of continuous positive airway pressure treatment and our reference group consisted of patients suffering from daytime somnolence, the hazard ratio of 4.04 for cardiovascular mortality in patients with moderate to severe disease is disturbingly high.

Ultrasonic evaluation of acute impact injury of articular cartilage in vitro.

OBJECTIVE: The aim of the study was to investigate whether high frequency ultrasound technique, originally designed for arthroscopic use can be utilized to detect traumatic cartilage injuries. METHODS: A total of four intact osteochondral plugs were prepared from eight patellas for parallel comparison (total of 32 plugs). The plugs were injured by dropping an impactor on them from heights of 2.5 cm, 5.0 cm, 10.0 cm and 15.0 cm (corresponding to impact energies of 0.12, 0.25 0.50 and 0.74 J, respectively), in a custom made dropping tower. The samples were imaged with a high frequency (40 MHz) ultrasound device before and after the injury. Reflection coefficient (R), integrated reflection coefficient (IRC), apparent integrated backscattering (AIB) and ultrasound roughness index (URI) were determined for each sample. RESULTS: Injuries invisible to the naked eye could be sensitively detected via the decreased values of the ultrasound reflection parameters (P < 0.05). Furthermore, a decreasing trend was detected in the values of R and IRC as the momentum of the impactor increased. The values of AIB were significantly lower for samples injured by dropping the impactor on the cartilage from heights of 2.5 cm and 15 cm but the URI values were similar in intact and injured cartilage. Histological analysis of the cartilage samples revealed that the injured cartilage exhibited depletion of the cartilage surface proteoglycans but the structure of collagen network was almost normal. CONCLUSIONS: Quantitative ultrasound imaging enables the detection of minor visually non-detectable cartilage injuries. As the present technique is feasible for arthroscopic use it might have clinical value in the evaluation of cartilage lesions during arthroscopy e.g., after tear of the anterior cruciate ligament.

Comparison of ultrasound and optical coherence tomography techniques for evaluation of integrity of spontaneously repaired horse cartilage.

The aim of this study was to compare sensitivity of ultrasound and optical coherence tomography (OCT) techniques for the evaluation of the integrity of spontaneously repaired horse cartilage. Articular surfaces of horse intercarpal joints, featuring both intact tissue and spontaneously healed chondral or osteochondral defects, were imaged ex vivo with arthroscopic ultrasound and laboratory OCT devices. Quantitative ultrasound (integrated reflection coefficient (IRC), apparent integrated backscattering coefficient (AIB) and ultrasound roughness index (URI)) and optical parameters (optical reflection coefficient (ORC), optical roughness index (ORI) and optical backscattering (OBS)) were determined and compared with histological integrity and mechanical properties of the tissue. Spontaneously healed tissue could be quantitatively discerned from the intact tissue with ultrasound and OCT techniques. Furthermore, several significant correlations (p < 0.05) were detected between ultrasound and OCT parameters. Superior resolution of OCT provided a more accurate measurement of cartilage surface roughness, while the ultrasound backscattering from the inner structures of the cartilage matched better with the histological findings. Since the techniques were found to be complementary to each other, dual modality imaging techniques could provide a useful tool for the arthroscopic evaluation of the integrity of articular cartilage.

Technical and practical improvements in arthroscopic indentation technique for diagnostics of articular cartilage softening.

Indentation measurements have been proposed to serve as sensitive in vivo diagnostics of cartilage degeneration. However, practical difficulties have hindered the use of quantitative indentation techniques during routine arthroscopies. In this study we modified the previously commercial indentation technique by designing software for quality control of manual indentations. With the modifications, our aim was to introduce more rapid and less erroneous measurements, as well as more automatic and objective analyses. The performance of the technique was tested in situ using six bovine medial tibial plateaus. All measurements were conducted by three operators. The intraoperator reproducibility was reasonable (CV%  = 7.1%) and the interoperator reproducibility was good (intraclass correlation coefficient  = 0.976). Further, the novel technique was tested by a single operator using 10 bovine medial tibial plateaus. The indentation stiffness values determined with the arthroscopic instrument correlated significantly with the dynamic (r = 0.823) and equilibrium (r = 0.752) moduli as well as tissue water (r =  -0.830) and hydroxyproline (r = 0.776) contents. To conclude, the novel measurement technique showed good reproducibility and was found to give valuable information on cartilage properties. Most importantly, the measurements and analyses were more straightforward and automatic than those introduced in the original indentation approach.

Effects of ultrasound beam angle and surface roughness on the quantitative ultrasound parameters of articular cartilage.

High-resolution arthroscopic ultrasound imaging provides a potential quantitative technique for the diagnostics of early osteoarthritis. However, an uncontrolled, nonperpendicular angle of an ultrasound beam or the natural curvature of the cartilage surface may jeopardize the reliability of the ultrasound measurements. We evaluated systematically the effect of inclining an articular surface on the quantitative ultrasound parameters. Visually intact (n = 8) and mechanically degraded (n = 6) osteochondral bovine patella samples and spontaneously fibrillated (n = 1) and spontaneously proteoglycan depleted (n = 1) osteochondral human tibial samples were imaged using a 50-MHz scanning acoustic system. The surface of each sample was adjusted to predetermined inclination angles (0, 2, 5 and 7 degrees ) and five ultrasound scan lines along the direction of the inclination were analyzed. For each scan line, reflection coefficient (R), integrated reflection coefficient (IRC) and ultrasound roughness index (URI) were calculated. Nonperpendicularity of the cartilage surface was found to affect R, IRC and URI significantly (p < 0.05). Importantly, all ultrasound parameters were able to distinguish (p < 0.05) the mechanically degraded samples from the intact ones even though the angle of incidence of the ultrasound beam varied between 0 and 5 degrees among the samples. Diagnostically, the present findings are important because the natural curvature of the articular surface varies, and a perfect perpendicularity between the ultrasound beam and the surface of the cartilage may be challenging to achieve in a clinical measurement.

Effect of bone marrow on acoustic properties of trabecular bone--3D finite difference modeling study.

The composition of bone marrow is influenced by many factors, such as age and diseases. The present numerical study investigates the contribution of marrow on the acoustic measurements of trabecular bone. Cylindrical bone samples (n = 11), extracted from three anatomical sites of human cadaver knees, were imaged with a high-resolution microtomography (microCT). Three-dimensional finite difference time domain (FDTD) models (Wave 3000 Pro 2.2, Cyberlogic Inc., NY, USA) were created using the segmented microCT images of each sample. First, we evaluated the effect of voxel size on the computer resource requirements, morphological parameters and acoustic simulations. Second, the effect of bone marrow on ultrasonic measurements was assessed. The simulations were repeated with two voxel sizes before and after substitution of bone marrow (i.e., fat) with water. The voxel size of the FDTD mesh controlled the fine structure of the modeled calcified matrix and significantly affected the simulation results. However, present simulations showed that the effect of bone marrow on ultrasound parameters can be reliably simulated with the applied voxel sizes of 72 and 90 microm. Ultrasound attenuation and speed were found (p < 0.01) to decrease and increase, respectively, when bone marrow was substituted with water. Moreover, reflection from the surface of the sample increased (p < 0.01) and backscatter from internal structures decreased (p < 0.01) after removal of marrow. The effect of bone marrow on the acoustic properties was stronger in samples with low bone volume fraction. The present results indicate that the amount and quality of bone marrow significantly influence the acoustic properties of trabecular bone. Possible interindividual differences in the composition of bone marrow may increase uncertainty in clinical ultrasound diagnostics of osteoporosis. Importantly, the effect is most significant in osteoporotic low-density bone.

Design, construction and evaluation of an ambulatory device for screening of sleep apnea.

Obstructive sleep apnea syndrome (OSAS) is a major public health problem. The golden reference for diagnosing OSAS is the sleep-laboratory based polysomnography (PSG). However, screening of population for OSAS may be practical and cost efficient only through ambulatory home recordings. In this work we aimed to design, construct and evaluate a novel ambulatory device for these recordings. The device was designed to record breathing movements, nasal and oral flow, position, snore, blood oxygen saturation and heart rate. The first part of clinical evaluation was done by recording 19 patients simultaneously with the novel device and with clinical reference instrumentation at a sleep laboratory. In the simultaneous recordings, no statistically significant difference was detected in the apnea-hypopnea index. All patients were correctly diagnosed, as compared to the reference instrumentation, with the novel ambulatory device. The second part of clinical evaluation was conducted through 323 ambulatory home recordings of which 275 (193 males and 82 females) were of diagnostically acceptable quality. A total of 106 and 169 recordings were successfully conducted with the novel device and a commercial ambulatory device, respectively. Both devices showed similar diagnostic capability in detecting sleep apnea. The novel device was found clinically applicable, technically reliable and sensitive for the diagnostics of OSAS.

Indentation diagnostics of cartilage degeneration.

OBJECTIVE: Mechanical indentation and ultrasound (US) indentation instruments have been introduced for quantitative assessment of cartilage properties in vivo. In this study, we compared capabilities of these instruments to determine properties of healthy and spontaneously degenerated human patellar cartilage in situ and to diagnose the early stages of osteoarthritis (OA). DESIGN: Six anatomical sites were localized from human patellae (N=14). By determining the force by which the tissue resists constant deformation (F(IND)), a mechanical indentation instrument was used to measure the compressive dynamic stiffness of cartilage. Further, the dynamic modulus (E(US)) and the US reflection coefficient of cartilage surface (R(US)) were measured with an US indentation instrument. For reference, Young's modulus and dynamic modulus were determined from cartilage disks using unconfined compression geometry. Proteoglycan and collagen contents of samples were analyzed microscopically. The samples were divided into three categories (healthy, early degeneration, and advanced degeneration) based on the Osteoarthritis Research Society International (OARSI) OA-grading. RESULTS: Parameters R(US), E(US) and F(IND) were significantly associated with the histological, compositional and mechanical properties of cartilage (|r|=0.28-0.72, n=73-75, P<0.05). Particularly, R(US) was able to discern degeneration of the samples with high sensitivity (0.77) and specificity (0.98). All parameters, except R(US,) showed statistically significant site-dependent variation in healthy cartilage. CONCLUSIONS: US reflection measurement shows potential for diagnostics of early OA as no site-matched reference values are needed. In addition, the high linear correlations between indentation and reference measurements suggest that these arthroscopic indentation instruments can be used for quantitative evaluation of cartilage mechanical properties, e.g., after cartilage repair surgery.