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 T1 rho 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 T1r 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. (C) 2019 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.Peer reviewe

Relationship between lower limb neuromuscular performanceand 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, mm3) was determined by data obtained from dualenergy X-ray absorptiometry. Data obtained using peripheral quantitative computed tomography was used to asses distal tibia compressive (BSId, g2/cm4) and tibial mid-shaft bending (SSImaxmid, mm3) strength indices. Results: After adjustment for height, weight and age, counter movement jump peak power production was the strongest independent predictor for Z (β=0.44; p<0.001) and for BSId (β=0.32; p=0.003). This was also true in concentric net impulse for Z (β=0.37; p=0.001) and for BSId (β=0.40; p<0.001). Additionally, knee extension force (β=0.30; p<0.001) and figure-of-eight-running test (β= -0.32; p<0.001) were among strongest independent predictors for BSId after adjustments. For SSImaxmid, concentric net impulse (β=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

Two novel direct SPIO labels and in vivo MRI detection of labeled cells after acute myocardial infarct

Background: Acute myocardial infarction (AMI) is a leading cause of morbidity and mortality worldwide. Cellular decay due hypoxia requires rapid and validated methods for possible therapeutic cell transplantation. Purpose: To develop direct and rapid superparamagnetic iron oxide (SPIO) cell label for a large-animal model and to assess in vivo cell targeting by magnetic resonance imaging (MRI) in an experimental AMI model. Material and Methods: Bone marrow mononuclear cells (BMMNCs) were labeled with SPIO particles using two novel direct labeling methods (rotating incubation method and electroporation). Labeling, iron incorporation in cells and label distribution, cellular viability, and proliferation were validated in vitro. An AMI porcine model was used to evaluate the direct labeling method (rotating incubation method) by examining targeting of labeled BMMNCs using MRI and histology. Results: Labeling (1 h) did not alter either cellular differentiation potential or viability of cells in vitro. Cellular relaxation values at 9.4 T correlated with label concentration and MRI at 1.5 T showing 894% signal reduction compared with non-labeled cells in vitro. In vivo, a high spatial correlation between MRI and histology was observed. The extent of macroscopic pathological myocardial changes (hemorrhage) correlated with altered function detected on MRI. Conclusion: We demonstrated two novel direct SPIO labeling methods and demonstrated the feasibility of clinical MRI for monitoring targeting of the labeled cells in animal models of AMI.Peer reviewe

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. (C) 2016 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.Peer reviewe

Treatment response of colorectal cancer liver metastases to neoadjuvant or conversion therapy : a prospective multicentre follow-up study using MRI, diffusion-weighted imaging and H-1-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 diffusionweighted imaging and H-1-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 KaplaneMeier 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). H-1-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.Peer reviewe

Treatment response of colorectal cancer liver metastases to neoadjuvant or conversion therapy : a prospective multicentre follow-up study using MRI, diffusion-weighted imaging and H-1-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 diffusionweighted imaging and H-1-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 KaplaneMeier 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). H-1-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.Peer reviewe

Treatment response of colorectal cancer liver metastases to neoadjuvant or conversion therapy: a prospective multicentre follow-up study using MRI, diffusion-weighted imaging and H-1-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 diffusionweighted imaging and H-1-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 KaplaneMeier 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). H-1-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.</p