Quantitative DCE-MRI Demonstrates Increased Blood Perfusion in Hoffa’s Fat Pad Signal Abnormalities in Knee Osteoarthritis

Knee osteoarthritis (OA) is one of the most prevalent chronic conditions affecting the adult population. OA is no longer thought to come from a purely biomechanical origin but rather one that has been increasingly recognized to include a persistent low-grade inflammatory component. Intra-articular corticosteroid injections (IACSI) have become a widely used method for treating pain in patients with OA as an effective symptomatic treatment. However, as the disease progresses, IACSI become ineffective. FKBP51 is a regulatory protein of the glucocorticoid receptor function and have been shown to be dysregulated in several pathological scenario’s including chronic inflammation. Despite of these facts, to our knowledge, there are no previous studies of the expression and possible role of FKBP51 in OA. We investigated by double and triple immunofluorescence confocal microscopy the cellular and subcellular expression of FKBP51 and its relations with inflammation factors in osteoarthritic knee joint tissues: specifically, in the tibial plateau knee cartilage, Hoffa’s fat pad and suprapatellar synovial tissue of the knee. Our results show co-expression of FKBP51 with TNF-α, IL-6, CD31 and CD34 in OA chondrocytes, synovial membrane cells and adipocytes in Hoffa’s fat pad. FKBP51 is also abundant in nerve fibers within the fat pad. Co-expression of FKBP51 protein with these markers may be indicative of its contribution to inflammatory processes and associated chronic pain in OA.

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Dynamic contrast-enhanced magnetic resonance imaging for monitoring neovascularization during bone regeneration—a randomized in vivo study in rabbits

Clinical Oral Investigations ◽

10.1007/s00784-021-03889-6 ◽

2021 ◽

Author(s):

L. A. R. Righesso ◽

M. Terekhov ◽

H. Götz ◽

M. Ackermann ◽

T. Emrich ◽

...

Keyword(s):

Magnetic Resonance Imaging ◽

Magnetic Resonance ◽

Bone Regeneration ◽

Blood Perfusion ◽

Autogenous Bone ◽

Resonance Imaging ◽

Dce Mri ◽

Dynamic Contrast Enhanced ◽

Contrast Enhanced

Abstract Objectives Micro-computed tomography (μ-CT) and histology, the current gold standard methods for assessing the formation of new bone and blood vessels, are invasive and/or destructive. With that in mind, a more conservative tool, dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), was tested for its accuracy and reproducibility in monitoring neovascularization during bone regeneration. Additionally, the suitability of blood perfusion as a surrogate of the efficacy of osteoplastic materials was evaluated. Materials and methods Sixteen rabbits were used and equally divided into four groups, according to the time of euthanasia (2, 3, 4, and 6 weeks after surgery). The animals were submitted to two 8-mm craniotomies that were filled with blood or autogenous bone. Neovascularization was assessed in vivo through DCE-MRI, and bone regeneration, ex vivo, through μ-CT and histology. Results The defects could be consistently identified, and their blood perfusion measured through DCE-MRI, there being statistically significant differences within the blood clot group between 3 and 6 weeks (p = 0.029), and between the former and autogenous bone at six weeks (p = 0.017). Nonetheless, no significant correlations between DCE-MRI findings on neovascularization and μ-CT (r =−0.101, 95% CI [−0.445; 0.268]) or histology (r = 0.305, 95% CI [−0.133; 0.644]) findings on bone regeneration were observed. Conclusions These results support the hypothesis that DCE-MRI can be used to monitor neovascularization but contradict the premise that it could predict bone regeneration as well.

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A comparative assessment of cartilage and joint fat pad as a potential source of cells for autologous therapy development in knee osteoarthritis

Rheumatology ◽

10.1093/rheumatology/kem217 ◽

2007 ◽

Vol 46 (11) ◽

pp. 1676-1683 ◽

Cited By ~ 102

Author(s):

A. English ◽

E. A. Jones ◽

D. Corscadden ◽

K. Henshaw ◽

T. Chapman ◽

...

Keyword(s):

Knee Osteoarthritis ◽

Comparative Assessment ◽

Fat Pad ◽

Potential Source ◽

Therapy Development ◽

Autologous Therapy

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Changes of the prefemoral fat pad associated with knee osteoarthritis

Physiotherapy ◽

10.1016/j.physio.2015.03.1327 ◽

2015 ◽

Vol 101 ◽

pp. e1383-e1384

Author(s):

K. Shibata ◽

K. Okada ◽

A. Saito ◽

I. Saito ◽

M. Wakasa ◽

...

Keyword(s):

Knee Osteoarthritis ◽

Fat Pad

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Dynamic contrast-enhanced MRI of synovitis in knee osteoarthritis: repeatability, discrimination and sensitivity to change in a prospective experimental study

European Radiology ◽

10.1007/s00330-021-07698-z ◽

2021 ◽

Author(s):

James W. MacKay ◽

Faezeh Sanaei Nezhad ◽

Tamam Rifai ◽

Joshua D. Kaggie ◽

Josephine H. Naish ◽

...

Keyword(s):

Knee Osteoarthritis ◽

Experimental Medicine ◽

Sensitivity To Change ◽

Dce Mri ◽

Dynamic Contrast Enhanced Mri ◽

Knee Oa ◽

Dynamic Contrast Enhanced ◽

Enhanced Mri ◽

Contrast Enhanced ◽

Contrast Enhanced Mri

Abstract Objectives Evaluate test-retest repeatability, ability to discriminate between osteoarthritic and healthy participants, and sensitivity to change over 6 months, of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) biomarkers in knee OA. Methods Fourteen individuals aged 40–60 with mild-moderate knee OA and 6 age-matched healthy volunteers (HV) underwent DCE-MRI at 3 T at baseline, 1 month and 6 months. Voxelwise pharmacokinetic modelling of dynamic data was used to calculate DCE-MRI biomarkers including Ktrans and IAUC60. Median DCE-MRI biomarker values were extracted for each participant at each study visit. Synovial segmentation was performed using both manual and semiautomatic methods with calculation of an additional biomarker, the volume of enhancing pannus (VEP). Test-retest repeatability was assessed using intraclass correlation coefficients (ICC). Smallest detectable differences (SDDs) were calculated from test-retest data. Discrimination between OA and HV was assessed via calculation of between-group standardised mean differences (SMD). Responsiveness was assessed via the number of OA participants with changes greater than the SDD at 6 months. Results Ktrans demonstrated the best test-retest repeatability (Ktrans/IAUC60/VEP ICCs 0.90/0.84/0.40, SDDs as % of OA mean 33/71/76%), discrimination between OA and HV (SMDs 0.94/0.54/0.50) and responsiveness (5/1/1 out of 12 OA participants with 6-month change > SDD) when compared to IAUC60 and VEP. Biomarkers derived from semiautomatic segmentation outperformed those derived from manual segmentation across all domains. Conclusions Ktrans demonstrated the best repeatability, discrimination and sensitivity to change suggesting that it is the optimal DCE-MRI biomarker for use in experimental medicine studies. Key Points • Dynamic contrast-enhanced MRI (DCE-MRI) provides quantitative measures of synovitis in knee osteoarthritis which may permit early assessment of efficacy in experimental medicine studies. • This prospective observational study compared DCE-MRI biomarkers across domains relevant to experimental medicine: test-retest repeatability, discriminative validity and sensitivity to change. • The DCE-MRI biomarker Ktransdemonstrated the best performance across all three domains, suggesting that it is the optimal biomarker for use in future interventional studies.

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