Treatment response of colorectal cancer liver metastases to neoadjuvant or conversion therapy: a prospective multicentre follow-up study using MRI, diffusion-weighted imaging and 1H-MR spectroscopy compared with histology (subgroup in the RAXO trial).

BACKGROUND: Colorectal cancer liver metastases respond to chemotherapy and targeted agents not only by shrinking, but also by morphologic and metabolic changes. The aim of this study was to evaluate the value of advanced magnetic resonance imaging (MRI) methods in predicting treatment response and survival. PATIENTS AND METHODS: We investigated contrast-enhanced MRI, apparent diffusion coefficient (ADC) in diffusion-weighted imaging and 1H-magnetic resonance spectroscopy (1H-MRS) in detecting early morphologic and metabolic changes in borderline or resectable liver metastases, as a response to first-line neoadjuvant or conversion therapy in a prospective substudy of the RAXO trial (NCT01531621, EudraCT2011-003158-24). MRI findings were compared with histology of resected liver metastases and Kaplan-Meier estimates of overall survival (OS). RESULTS: In 2012-2018, 52 patients at four Finnish university hospitals were recruited. Forty-seven patients received neoadjuvant or conversion chemotherapy and 40 liver resections were carried out. Low ADC values (below median) of the representative liver metastases, at baseline and after systemic therapy, were associated with partial response according to RECIST criteria, but not with morphologic MRI changes or histology. Decreasing ADC values following systemic therapy were associated with improved OS compared to unchanged or increasing ADC, both in the liver resected subgroup (5-year OS rate 100% and 34%, respectively, P = 0.022) and systemic therapy subgroup (5-year OS rate 62% and 23%, P = 0.049). 1H-MRS revealed steatohepatosis induced by systemic therapy. CONCLUSIONS: Low ADC values at baseline or during systemic therapy were associated with treatment response by RECIST but not with histology, morphologic or detectable metabolic changes. A decreasing ADC during systemic therapy is associated with improved OS both in all patients receiving systemic therapy and in the resected subgroup.

Machine learning classification on texture analyzed T2 maps of osteoarthritic cartilage: oulu knee osteoarthritis study.

OBJECTIVE: To introduce local binary pattern (LBP) texture analysis to cartilage osteoarthritis (OA) research and compare the performance of different classification systems in discrimination of OA subjects from healthy controls using gray-level co-occurrence matrix (GLCM) and LBP texture data. Classification algorithms were used to reduce the dimensionality of texture data into a likelihood of subject belonging to the reference class. METHOD: T2 relaxation time mapping with multi-slice multi-echo spin echo sequence was performed for eighty symptomatic OA patients and 63 asymptomatic controls on a 3T clinical MRI scanner. Relaxation time maps were subjected to GLCM and LBP texture analysis, and classification algorithms were deployed with an in-house developed software. Implemented algorithms were K nearest neighbors, support vector machine, and neural network classifier. RESULTS: LBP and GLCM discerned OA patients from controls with a significant difference in all studied regions. Classification models comprising GLCM and LBP showed high accuracy in classing OA patients and controls. The best performance was obtained with a multilayer perceptron type classifier with an overall accuracy of 90.2 %. CONCLUSION: LBP texture analysis complements prior results with GLCM, and together LBP and GLCM serve as significant input data for classification algorithms trained for OA assessment. Presented algorithms are adaptable to versatile OA evaluations also for future gradational or predictive approaches.

Defective WNT signaling may protect from articular cartilage deterioration - a quantitative MRI study on subjects with a heterozygous WNT1 mutation.

OBJECTIVE: WNT signaling is of key importance in chondrogenesis and defective WNT signaling may contribute to the pathogenesis of osteoarthritis and other cartilage diseases. Biochemical composition of articular cartilage in patients with aberrant WNT signaling has not been studied. Our objective was to assess the knee articular cartilage in WNT1 mutation-positive individuals using a 3.0T MRI unit to measure cartilage thickness, relaxation times, and texture features. DESIGN: Cohort comprised mutation-positive (N = 13; age 17-76 years) and mutation-negative (N = 13; 16-77 years) subjects from two Finnish families with autosomal dominant WNT1 osteoporosis due to a heterozygous missense mutation c.652T>G (p.C218G) in WNT1. All subjects were imaged with a 3.0T MRI unit and assessed for cartilage thickness, T2 and T1ρ relaxation times, and T2 texture features contrast, dissimilarity and homogeneity of T2 relaxation time maps in six regions of interest (ROIs) in the tibiofemoral cartilage. RESULTS: All three texture features showed opposing trends with age between the groups in the medial tibiofemoral cartilage (P = 0.020-0.085 for the difference of the regression coefficients), the mutation-positive individuals showing signs of cartilage preservation. No significant differences were observed in the lateral tibiofemoral cartilage. Cartilage thickness and means of T2 relaxation time did not differ between groups. Means of T1ρ relaxation time were significantly different in one ROI but the regression analysis displayed no differences. CONCLUSIONS: Our results show less age-related cartilage deterioration in the WNT1 mutation-positive than the mutation-negative subjects. This suggests, that the WNT1 mutation may alter cartilage turnover and even have a potential cartilage-preserving effect.

Assessment of meniscus with adiabatic T1ρ and T2ρ relaxation time in asymptomatic subjects and patients with mild osteoarthritis: a feasibility study.

OBJECTIVE: To investigate the ability of magnetic resonance imaging (MRI) adiabatic relaxation times in the rotating frame (adiabatic T1ρ and T2ρ) to detect structural alterations in meniscus tissue of mild OA patients and asymptomatic volunteers. METHOD: MR images of 24 subjects (age range: 50-67 years, 12 male), including 12 patients with mild osteoarthritis (OA) (Kellgren-Lawrence (KL) = 1, 2) and 12 asymptomatic volunteers, were acquired using a 3 T clinical MRI system. Morphological assessment was performed using semiquantitative MRI OA Knee Score (MOAKS). Adiabatic T1ρ and T2ρ (AdT1ρ, AdT2ρ) relaxation time maps were calculated in regions of interest (ROIs) containing medial and lateral horns of menisci. The median relaxation time values of the ROIs were compared between subjects classified based on radiographic findings and MOAKS evaluations. RESULTS: MOAKS assessment of patients and volunteers indicated the presence of meniscal and cartilage lesions in both groups. For the combined cohort group, prolonged AdT1ρ was observed in the posterior horn of the medial meniscus (PHMED) in subjects with MOAKS meniscal tear (P < 0.05). AdT2ρ was statistically significantly longer in PHMED of subjects with MOAKS full-thickness cartilage loss (P < 0.05). After adjusting for multiple comparisons, differences in medians of observed AdT1ρ and AdT2ρ values between mild OA patients and asymptomatic volunteers did not reach statistical significance. CONCLUSION: AdT1ρ and AdT2ρ measurements have the potential to identify changes in structural composition of meniscus tissue associated with meniscal tear and cartilage loss in a cohort group of mild OA patients and asymptomatic volunteers.

Effects of high intensity resistance aquatic training on body composition and walking speed in women with mild knee osteoarthritis: a 4-month RCT with 12-month follow-up.

OBJECTIVE: To investigate the effects of 4-months intensive aquatic resistance training on body composition and walking speed in post-menopausal women with mild knee osteoarthritis (OA), immediately after intervention and after 12-months follow-up. Additionally, influence of leisure time physical activity (LTPA) will be investigated. DESIGN: This randomised clinical trial assigned eighty-seven volunteer postmenopausal women into two study arms. The intervention group (n = 43) participated in 48 supervised intensive aquatic resistance training sessions over 4-months while the control group (n = 44) maintained normal physical activity. Eighty four participants continued into the 12-months' follow-up period. Body composition was measured with dual-energy X-ray absorptiometry (DXA). Walking speed over 2 km and the knee injury and osteoarthritis outcome score (KOOS) were measured. LTPA was recorded with self-reported diaries. RESULTS: After the 4-month intervention there was a significant decrease (P = 0.002) in fat mass (mean change: -1.17 kg; 95% CI: -2.00 to -0.43) and increase (P = 0.002) in walking speed (0.052 m/s; 95% CI: 0.018 to 0.086) in favour of the intervention group. Body composition returned to baseline after 12-months. In contrast, increased walking speed was maintained (0.046 m/s; 95% CI 0.006 to 0.086, P = 0.032). No change was seen in lean mass or KOOS. Daily LTPA over the 16-months had a significant effect (P = 0.007) on fat mass loss (f2 = 0.05) but no effect on walking speed. CONCLUSIONS: Our findings show that high intensity aquatic resistance training decreases fat mass and improves walking speed in post-menopausal women with mild knee OA. Only improvements in walking speed were maintained at 12-months follow-up. Higher levels of LTPA were associated with fat mass loss. TRIAL REGISTRATION NUMBER: ISRCTN65346593.

Effect of progressive high-impact exercise on femoral neck structural strength in postmenopausal women with mild knee osteoarthritis: a 12-month RCT.

It is uncertain whether subjects with mild knee osteoarthritis, and who may be at risk of osteoporosis, can exercise safely with the aim of improving hip bone strength. This RCT showed that participating in a high-impact exercise program improved femoral neck strength without any detrimental effects on knee cartilage composition. INTRODUCTION: No previous studies have examined whether high-impact exercise can improve bone strength and articular cartilage quality in subjects with mild knee osteoarthritis. In this 12-month RCT, we assessed the effects of progressive high-impact exercise on femoral neck structural strength and biochemical composition of knee cartilage in postmenopausal women. METHODS: Eighty postmenopausal women with mild knee radiographic osteoarthritis were randomly assigned into the exercise (n = 40) or control (n = 40) group. Femoral neck structural strength was assessed with dual-energy X-ray absorptiometry. The knee cartilage region exposed to exercise loading was measured by the quantitative MRI techniques of T2 mapping and delayed gadolinium-enhanced MRI of cartilage (dGEMRIC). Also, an accelerometer-based body movement monitor was used to evaluate the total physical activity loading on the changes of femoral neck strength in all participants. Training effects on the outcome variables were estimated by the bootstrap analysis of covariance. RESULTS: A significant between-group difference in femoral neck bending strength in favor of the trainees was observed after the 12-month intervention (4.4%, p < 0.01). The change in femoral neck bending strength remained significant after adjusting for baseline value, age, height, and body mass (4.0%, p = 0.020). In all participants, the change in bending strength was associated with the total physical activity loading (r = 0.29, p = 0.012). The exercise participation had no effect on knee cartilage composition. CONCLUSION: The high-impact training increased femoral neck strength without having any harmful effect on knee cartilage in women with mild knee osteoarthritis. These findings imply that progressive high-impact exercise is a feasible method in seeking to prevent hip fractures in postmenopausal women whose articular cartilage may also be frail.

Efficacy of progressive aquatic resistance training for tibiofemoral cartilage in postmenopausal women with mild knee osteoarthritis: a randomised controlled trial.

OBJECTIVE: To study the efficacy of aquatic resistance training on biochemical composition of tibiofemoral cartilage in postmenopausal women with mild knee osteoarthritis (OA). DESIGN: Eighty seven volunteer postmenopausal women, aged 60-68 years, with mild knee OA (Kellgren-Lawrence grades I/II and knee pain) were recruited and randomly assigned to an intervention (n = 43) and control (n = 44) group. The intervention group participated in 48 supervised aquatic resistance training sessions over 16 weeks while the control group maintained usual level of physical activity. The biochemical composition of the medial and lateral tibiofemoral cartilage was estimated using single-slice transverse relaxation time (T2) mapping and delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC index). Secondary outcomes were cardiorespiratory fitness, isometric knee extension and flexion force and knee injury and OA outcome (KOOS) questionnaire. RESULTS: After 4-months aquatic training, there was a significant decrease in both T2 -1.2 ms (95% confidence interval (CI): -2.3 to -0.1, P = 0.021) and dGEMRIC index -23 ms (-43 to -3, P = 0.016) in the training group compared to controls in the full thickness posterior region of interest (ROI) of the medial femoral cartilage. Cardiorespiratory fitness significantly improved in the intervention group by 9.8% (P = 0.010). CONCLUSIONS: Our results suggest that, in postmenopausal women with mild knee OA, the integrity of the collagen-interstitial water environment (T2) of the tibiofemoral cartilage may be responsive to low shear and compressive forces during aquatic resistance training. More research is required to understand the exact nature of acute responses in dGEMRIC index to this type of loading. Further, aquatic resistance training improves cardiorespiratory fitness. TRIAL REGISTRATION NUMBER: ISRCTN65346593.

Regional dGEMRIC analysis in patients at risk of osteoarthritis provides additional information about activity related changes in cartilage structure.

BACKGROUND: Previously, a positive effect of exercise on cartilage structure was indicated with delayed gadolinium-enhanced magnetic resonance imaging (MRI) of cartilage (dGEMRIC). However, in that study only one full-thickness region of interest (ROI) in the medial femoral condyle was analyzed. PURPOSE: To improve the knowledge about exercise effects on cartilage structure by re-analyzing previous images with regional dGEMRIC analysis. MATERIAL AND METHODS: Thirty patients (age range, 38-50 years) with a previous medial meniscus resection were divided into three groups according to self-reported change in physical activity (PA) level in a 4-month exercise intervention study: Group I (n = 11), increased PA level; Group II (n = 13), no change in PA level; and Group III (n = 6), reduced PA level. dGEMRIC index was analyzed at inclusion and after 4 months. Anterior (less load) and posterior (more load) ROIs of medial and lateral femoral condyles were analyzed, as well as superficial and deep cartilage regions. RESULTS: Group I increased the dGEMRIC index in the posterior cartilage (P = 0.004). The increase was larger in the lateral (P = 0.005) than the medial compartment in both superficial and deep cartilage regions. The dGEMRIC index did not change in Group II. In Group III, the dGEMRIC index decreased in the medial posterior cartilage (P = 0.03). CONCLUSION: In patients with a previous medial meniscectomy, the beneficial effect of exercise varies between different locations within the joint, the largest improvement being observed in lateral posterior cartilage, i.e. the load-bearing cartilage in the compartment without a meniscus lesion. The effects of exercise do not seem to vary with cartilage depth.

Bone and cartilage characteristics in postmenopausal women with mild knee radiographic osteoarthritis and those without radiographic osteoarthritis.

OBJECTIVES: To evaluate the association between radiographically-assessed knee osteoarthritis and femoral neck bone characteristics in women with mild knee radiographic osteoarthritis and those without radiographic osteoarthritis. METHODS: Ninety postmenopausal women (mean age [SD], 58 [4] years; height, 163 [6] cm; weight, 71 [11] kg) participated in this cross-sectional study. The severity of radiographic knee osteoarthritis was defined using Kellgren-Lawrence grades 0=normal (n=12), 1=doubtful (n=25) or 2=minimal (n=53). Femoral neck bone mineral content (BMC), section modulus (Z), and cross-sectional area (CSA) were measured with DXA. The biochemical composition of ipsilateral knee cartilage was estimated using quantitative MRI measures, T2 mapping and dGEMRIC. The associations between radiographic knee osteoarthritis grades and bone and cartilage characteristics were analyzed using generalized linear models. RESULTS: Age-, height-, and weight-adjusted femoral neck BMC (p for linearity=0.019), Z (p for linearity=0.033), and CSA (p for linearity=0.019) increased significantly with higher knee osteoarthritis grades. There was no linear relationship between osteoarthritis grades and knee cartilage indices. CONCLUSIONS: Increased DXA assessed hip bone strength is related to knee osteoarthritis severity. These results are hypothesis driven that there is an inverse relationship between osteoarthritis and osteoporosis. However, MRI assessed measures of cartilage do not discriminate mild radiographic osteoarthritis severity.

Relationship between lower limb neuromuscular performance and bone strength in postmenopausal women with mild knee osteoarthritis.

OBJECTIVES: To investigate whether neuromuscular performance predicts lower limb bone strength in different lower limb sites in postmenopausal women with mild knee osteoarthritis (OA). METHODS: Neuromuscular performance of 139 volunteer women aged 50-68 with mild knee OA was measured using maximal counter movement jump test, isometric knee flexion and extension force and figure-of-eight-running test. Femoral neck section modulus (Z, mm(3)) was determined by data obtained from dual-energy X-ray absorptiometry. Data obtained using peripheral quantitative computed tomography was used to asses distal tibia compressive (BSId, g(2)/cm(4)) and tibial mid-shaft bending (SSImax(mid), mm(3)) strength indices. RESULTS: After adjustment for height, weight and age, counter movement jump peak power production was the strongest independent predictor for Z (ß=0.44; p<0.001) and for BSId (ß=0.32; p=0.003). This was also true in concentric net impulse for Z (ß=0.37; p=0.001) and for BSId (ß=0.40; p<0.001). Additionally, knee extension force (ß=0.30; p<0.001) and figure-of-eight-running test (ß= -0.32; p<0.001) were among strongest independent predictors for BSId after adjustments. For SSImax(mid), concentric net impulse (ß=0.33; p=0.002) remained as the strongest independent predictor after adjustments. CONCLUSIONS: Neuromuscular performance in postmenopausal women with mild knee OA predicted lower limb bone strength in every measured skeletal site.

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).

Is cartilage sGAG content related to early changes in cartilage disease? Implications for interpretation of dGEMRIC.

OBJECTIVE: This study investigates sulphated glycosaminoglycans (sGAG) content changes in early osteoarthritis (OA), and whether contrast-enhanced magnetic resonance imaging (MRI) of cartilage in vitro may identify early event of OA pathology. METHOD: Osteochondral plugs from patients with hip OA or femoral neck fracture (reference group) were collected and analysed by 1.5 T MRI with ΔR1 as a measure of cartilage contrast concentration. Cartilage hydration, contents of sGAG, cartilage oligomeric matrix protein (COMP), hydroxyproline, denatured collagen, and aggrecan TEGE(392) neoepitope were determined and histological grading was performed. RESULTS: sGAG content correlated to ΔR1, although no difference in either of these parameters was detectable between OA and reference cartilage at 4 h of contrast equilibration. In contrast, biochemical analysis of other cartilage matrix constituents showed distinct alterations typical for early cartilage degradation in OA cartilage and with clear evidence for increased aggrecan turnover. CONCLUSION: In the present in vitro study, cartilage sGAG content could not distinguish between early OA cartilage and reference cartilage. Given, that delayed gadolinium enhanced MRI of cartilage (dGEMRIC) indicates early events in the pathogenesis of OA in vivo, our results from the in vitro studies imply other, additional factors than cartilage sGAG content, e.g., alterations in diffusion or increased supply of contrast agent in the diseased joint. Alternatively, an altered dGEMRIC reflects later stages of OA, when sGAG content decreases. Further investigations are warranted, to understand variations in sGAG content in pathology, an essential background for interpreting dGEMRIC measurements.

Dual-energy digital radiography in the assessment of bone mechanical properties.

At present, bone fragility and fracture risk are estimated with bone mineral density (BMD), measured by dual-energy x-ray absorptiometry (DXA). It is known that DXA-based BMD (BMD(DXA)) has a relationship with mechanical characteristics of bone. Dual-energy digital radiography (DEDR) has also been shown to be a potential method to determine BMD, but the ability of DEDR-based BMD (BMD(DEDR)) to predict bone mechanical properties is not yet known. In this study, we investigated the ability of BMD(DEDR) to predict the mechanical characteristics of bone. Reindeer femora (N = 50) were imaged at two different energies (79 and 100 kV(p)) using a clinical digital radiography system. BMD was determined in four regions from these images using the DXA calculation principle. Femora were mechanically tested using axial loading configuration. Mechanical parameters were correlated with the BMD(DEDR) and BMD(DXA) of the femoral neck (FNBMD(DEDR) and FNBMD(DXA)). FNBMD(DEDR) and FNBMD(DXA) both correlated moderately with mechanical parameters. The highest correlations were found with maximal load (r = 0.53 and r = 0.65, p < 0.01, respectively). No statistically significant differences were found between the correlation coefficients when comparing the FNBMD(DEDR) or FNBMD(DXA) values and mechanical parameters. The correlation coefficient between BMD(DEDR) and BMD(DXA) varied between r = 0.56 and 0.86 (p < 0.01) in different regions of the upper femur. In conclusion, BMD(DEDR) predicts the mechanical parameters of reindeer bone with similar accuracy as BMD(DXA).

Reproducibility of imaging human knee cartilage by delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) at 1.5 Tesla.

OBJECTIVE: The purpose of this study was to investigate the day-to-day reproducibility of the delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) measurement at different knee joint surfaces in healthy subjects at 1.5 Tesla (T). METHODS: The dGEMRIC experiment was repeated for 10 asymptomatic volunteers three times with an average interval of 5 days between scans. The measurement was performed from a single sagittal slice through the center of the lateral femoral condyle and from the center of the patella in the axial plane. Cartilage was manually segmented into superficial, deep and full-thickness regions of interests (ROIs) at different topographical locations of the femur, tibia and patella. The reproducibility was evaluated separately for each ROI as well as for the entire bulk cartilage in the slice of each joint surface. RESULTS: The reproducibility at various ROIs expressed by root-mean-square average coefficient of variation (CV(RMS)) ranged between 4.7-12.9%. Thirty out of thirty-three ROIs showed a CV(RMS) less than 10%. Intraclass correlation coefficient (ICC) ranged between 0.45 and 0.98. The CV(RMS) and ICC for bulk dGEMRIC were 4.2% and 0.95 for femur, 5.5% and 0.87 for tibia, and 4.8% and 0.97 for patella. CONCLUSIONS: The dGEMRIC technique showed good day-to-day reproducibility, on the average 8% for small deep or superficial segments, 7% for full-thickness ROIs and 5% for bulk ROIs covering all visible cartilage in a single joint surface. We conclude that dGEMRIC imaging at field strength 1.5 T can be used as a reliable instrument for the assessment of articular cartilage when staff has been carefully trained.

T2, Carr-Purcell T2 and T1rho of fat and water as surrogate markers of trabecular bone structure.

Magnetic resonance imaging (MRI) techniques have been developed for non-invasive assessment of the structural properties of trabecular bone. These measurements, however, suffer from relatively long acquisition times and low resolution compared to the trabecular size. Spectroscopic measurement of relaxation times could be applied for more detailed and faster assessment of relaxation properties of bone marrow and also provide surrogate information on trabecular structure. In the present study, bovine trabecular bone was investigated with spectroscopic NMR (nuclear magnetic resonance) methods to determine the relationship between structural parameters as measured with micro-CT and T(2), Carr-Purcell T(2) and T(1rho) relaxation times of fat and water. To compare bone with a sample matrix with magnetic susceptibility interfaces, phantoms consisting of glass beads with different diameters in oil or water were used. The behavior of T(2) measured with different sequences and T(1rho) at different magnitudes of spin-lock fields were characterized, and relaxation times were correlated with structural parameters. T(2) and T(1rho) showed significant associations with structural bone parameters. Strongest linear correlations (r = 0.81, p < 0.01) were established between R(1rho) (1/T(1rho)) of fat component and structural model index. For glass beads, the behavior of T(2) and T(1rho) was similar to that of the water compartment of bone marrow. The present results suggest feasibility of spectroscopic NMR measurements to assess trabecular structure. However, further studies are required to determine the sensitivity of this approach to fat content of bone marrow and to lower the field strengths used in clinical devices.

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.

Quantitative MRI of parallel changes of articular cartilage and underlying trabecular bone in degeneration.

OBJECTIVE: To determine the interrelations between degenerative changes in articular cartilage and underlying trabecular bone during development of osteoarthritis and to test the ability of quantitative magnetic resonance imaging (MRI) to detect those changes. METHODS: Human cadaver patellae were investigated with quantitative MRI methods, T(2) and dGEMRIC, at 1.5T. Same measurements for isolated cartilage samples were performed at 9.4T. Bone samples, taken at sites matched with cartilage analyses, were measured with MRI and peripheral quantitative computed tomography (pQCT). Mechanical and quantitative microscopic methods were also utilized for both cartilage and bone samples. RESULTS: Significant differences were found between the samples with different stages of degeneration in mechanical properties, T(2) at 1.5T and proteoglycan (PG) content of articular cartilage. dGEMRIC at 9.4T discerned samples with advanced degeneration from the others. Bone variables measured with pQCT discerned samples with no or minimal and advanced degeneration, and mechanical properties of trabecular bone discerned samples with no or minimal degeneration from the others. Significant linear correlations were found between the bone and cartilage parameters. Characteristically, associations between variables were stronger within the samples with no or minimal degeneration compared to all samples. CONCLUSIONS: Quantitative MRI variables, especially T(2) relaxation time of articular cartilage, may be feasible surrogate markers for early and advanced osteoarthritic changes in joint tissues, including decreased elastic moduli, PG and collagen contents of cartilage and mineral density and volume fraction of trabecular bone. Further work is required to resolve the relaxation mechanisms at clinically applicable field strengths.

Prediction of mechanical properties of trabecular bone using quantitative MRI.

Techniques for quantitative magnetic resonance imaging (MRI) have been developed for non-invasive estimation of the mineral density and structure of trabecular bone. The R*(2) relaxation rate (i.e. 1/T*(2)) is sensitive to bone mineral density (BMD) via susceptibility differences between trabeculae and bone marrow, and by binarizing MRI images, structural variables, such as apparent bone volume fraction, can be assessed. In the present study, trabecular bone samples of human patellae were investigated in vitro at 1.5 T to determine the ability of MRI-derived variables (R*(2) and bone volume fraction) to predict the mechanical properties (Young's modulus, yield stress and ultimate strength). Further, the MRI variables were correlated with reference measurements of volumetric BMD and bone area fraction as determined with a clinical pQCT system. The MRI variables correlated significantly (p < 0.01) with the mechanical variables (r = 0.32-0.46), BMD (r = 0.56) and bone structure (r = 0.51). A combination of R*(2) and MRI-derived bone volume fraction further improved the prediction of yield stress and ultimate strength. Although pQCT showed a trend towards better prediction of the mechanical properties, current results demonstrate the feasibility of combined MR imaging of marrow susceptibility and bone volume fraction in predicting the mechanical strength of trabecular bone and bone mineral density.

T2 relaxation time and delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) of human patellar cartilage at 1.5 T and 9.4 T: Relationships with tissue mechanical properties.

Quantitative magnetic resonance imaging (MRI) techniques have been developed for noninvasive assessment of the structure of articular cartilage. T2 relaxation time is sensitive to the integrity and orientation of the collagen network, while T1 relaxation time in presence of Gd-DTPA2- (dGEMRIC) reflects the proteoglycan content of cartilage. In the present study, human patellar cartilage samples were investigated in vitro to determine the ability of MRI parameters to reveal topographical variations and to predict mechanical properties of cartilage at two different field strengths. T2 and dGEMRIC measurements at 1.5 T and 9.4 T were correlated with the static and dynamic compressive moduli at six anatomical locations of the patellar surface. Statistically significant linear correlations were observed between MRI and mechanical parameters at both field strengths, especially between T2 and Young's modulus. No significant difference was found between the T2 measurements at different field strengths in predicting mechanical properties of the tissue. Topographical variation of T2 values at both field strengths was similar to that of Young's moduli. The current results demonstrate the feasibility of quantitative MRI, particularly T2 mapping, to reflect the mechanical properties of human patellar cartilage at both field strengths.