High-resolution/high-contrast MRI of human articular cartilage lesions.

BACKGROUND: Magnetic resonance microscopy (MRM) is an important experimental tool in the identification of early cartilage lesions. METHODS: Normal and degenerated cartilage samples were imaged at 11.74 T using a standard spin echo sequence. Quantitative MR measurements for T1, T2, and ADC were obtained and mapping for T2 and ADC was performed. The bi-exponential model for T2 relaxation was also explored. Histology was carried out for comparison with MR images. RESULTS: MR images of cartilage samples displaying early stages of degeneration were positively correlated to their histological appearance in 23-microm high-resolution images and also with much shorter imaging times at 47-microm resolution. T2 maps enable delineation of the actual cartilage zones, distinguishing the superficial zone in particular. The bi-exponential model can reflect cartilage components at different stages of degeneration. INTERPRETATION: At 11.74 T, with 23-microm resolution or with 47-microm resolution and shorter imaging times, MRM provides images that allow visualization of early stages of cartilage degeneration, including superficial fibrillation. This has not been shown previously. The images also allow quantitative measurements (T1, T2, and ADC) in each cartilage region, which can be indicative of different stages of cartilage degeneration

Total ankle replacement : Clinical, radiological, and biochemical assessment with special reference to osteolysis

End-stage ankle arthritis may be managed surgically with either ankle fusion or total ankle replacement (TAR). The results of total ankle replacement have improved over the recent decades, but challenges remain. Peri-implant osteolysis has been major problem, as it compromises the stability of the implant components and can lead to aseptic loosening and implant failure. For this retrospective study, 164 ankles (34 Scandinavian Total Ankle Replacement (STAR) and 130 Ankle Evolutive System (AES)) operated on in single institution during 1997–2008 were followed clinically and radiologically. Histological samples were collected from ankles revised due to periprosthetic osteolysis. Analysis from the data covering the years 1997–2006 of the Finnish Arthroplasty Registry was conducted. The peri-implant osteolysis was quite common in the AES total ankle implants: 70% of the ankles exhibited osteolysis at the latest follow-up. Dual-coating of the implant was associated with a 3.1-fold risk of osteolysis and of significantly earlier development of osteolysis compared to single-coating. Histology revealed a foreign-body reaction characterized by extensive soft and bone tissue necrosis. RANK/RANKL-mediated osteoclast and multinuclear foreign body giant cells contributed to peri-implant osteolysis, and there was increased expression of danger signals in the peri-implant tissues, suggesting an auto-inflammation mechanism behind osteolysis. The annual incidence of TAR according to the Finnish Arthroplasty Registry was 1.5 per 105 inhabitants and overall implant survival was 83% at 5 years when any revision was the end point. The most common reasons for revision were aseptic loosening (39%) and instability (39%). In the registry study, there was no difference in the survival rates between the STAR and AES designs, nor was there any association between age, gender, diagnosis, or hospital volume and TAR survival. The survival of the STAR implant was satisfactory, 93.8% (95% CI 77.5% to 98.4%) at 5 years, and 87.2% (95% CI 69.4% to 95.0%) at 10 and 15 years. There was no statistically significant association between implant survival and patient age, gender, BMI, or diagnosis. The overall rate of revisions was 44%, which includes all postoperative revisions for osteolysis, component and insert exchanges, and conversions to arthrodesis. The survival of the AES implant was strongly affected by osteolysis and malalignment, and inferior compared to previously published results. The 5-year survival was 87.3% (95% CI 80.0% to 92.0%), and the 10-year survival 74.9% (95% CI 65.4% to 82.2%). Postoperative alignment of ≥10º of varus predicted a poorer outcome and was statistically significant for implant survival (p=0.0005). The revision rate for all revisions was 57% including all postoperative revisions for osteolysis, component exchanges, and conversions to arthrodesis. Osteolysis was the main reason for revisions and failure. The survival of the STAR total ankle replacement was satisfactory in the long-term, but the results of the AES total ankle implants were strongly influenced by aggressive and early-emerging osteolysis. Future studies should focus on examining the mechanism behind the osteolytic process in TAR to avoid similar problems for implant development in the future.Nilkan tekonivel: Kliininen, radiologinen ja biokemiallinen seuranta Ylemmän nilkkanivelen loppuvaiheen nivelrikkoa voidaan hoitaa nilkan luudutus- tai tekonivelleikkauksella. Viime parinkymmenen vuoden aikana nilkan tekonivelleikkaus tuhoutuneen ylemmän nilkkanivelen hoidossa on yleistynyt. Hankalin nilkan tekonivelen komplikaatio on viime vuosien aikana ollut osteolyysi eli luun liukeneminen tekonivelen ympäriltä, joka saattaa johtaa tekonivelen irtoamiseen. Tässä takautuvassa tutkimuksessa analysoitiin yhdessä sairaalassa laitetun 164 nilkan tekonivelen (34 Scandinavian Total Ankle Replacement (STAR) ja 130 Ankle Evolutive System (AES)) kliiniset ja radiologiset seurantatulokset. Kudosnäytteet saatiin nilkoista, jotka oli jouduttu uusintaleikkaamaan osteolyysin vuoksi. Lisäksi analysoitiin Suomen Endoproteesirekisterin dataa ajalta 1997–2006 koskien nilkan tekoniveliä. Osteolyysin määrä AES-nilkan tekonivelissä oli korkea, 70 % nilkoista viimeksi tehdyn analyysin mukaan. AES-tekonivelen kaksoispinnoite aiheutti yli kolminkertaisen riskin osteolyysin kehittymiselle sekä merkitsevästi aikaisemmin ilmaantuvaa osteolyysiä yksinkertaiseen pinnoitteeseen verrattuna. Mikroskooppitutkimuksessa todettiin vierasesinereaktio ja runsaasti kudoskuoliota. Suomen Endoproteesirekisteriin perustuvassa tutkimuksessa nilkan tekonivelen vuosittainen ilmaantuvuus oli 1,5 tapausta 100.000 asukasta kohti. Nilkkaproteesin kokonaispysyvyys oli 83 % 5 vuoden aikana, kun päätetapahtumana oli mikä tahansa uusintaleikkaus. Uusintaleikkauksen yleisimmät syyt olivat aseptinen irtoaminen (39 %) ja epävakaus (39 %). Rekisteritutkimuksen mukaan implanttimallilla, potilaan iällä, sukupuolella, diagnoosilla tai sairaalan leikkausvolyymilla ei ollut yhteyttä implantin pysyvyyteen. STAR-nilkan tekonivelen pysyvyyden todettiin olevan erittäin hyvä, 93.8 % viiden vuoden ja 87,2 % kymmenen ja viidentoista vuoden aikana. Potilan iällä, sukupuolella, painoindeksillä tai diagnoosilla ei todettu yhteyttä tekonivelen pysyvyyteen. Uusintaleikkausten määrä oli 44 % sisältäen kaikki uusintaleikkaukset osteolyysin vuoksi, komponenttien vaihdot ja tekonivelen vaihdot luudutukseen. AES-nilkan tekonivelen pysyvyys oli huonoa, ja siihen vaikuttivat sekä runsas osteolyysin määrä että nilkan virheasento. Viiden vuoden pysyvyys oli 87.3 % ja kymmenen vuoden 74.9 %. Leikkauksen jälkeisen nilkan virhelinjauksen todettiin ennustavan tilastollisesti merkitsevästi huonompaa tulosta. Uusintaleikkausten määrä oli 57 % sisältäen kaikki uusintaleikkaukset osteolyysin vuoksi, komponenttien vaihdot ja tekonivelen vaihdot luudutukseen. Osteolyysi aiheutti suurimman osan uusintaleikkauksista ja epäonnistumisista. STAR-tekonivelen pysyvyys oli hyvä pitkällä aikavälillä, mutta AES-tekonivelen tuloksia huononsi merkitsevästi erittäin aikaisessa vaiheessa ilmaantunut aggressiivinen osteolyysi. Tulevaisuudessa tutkimusten tulisi keskittyä selvittämään tarkemmin osteolyysin mekanismeja, jotta vastaavat ongelmat voitaisiin jatkossa välttää tekonivelien kehitystyössä.Siirretty Doriast

Toward New Assessment of Knee Cartilage Degeneration

Funding Information: The authors would like to thank the project RESTORE for their contribution to this study, Marco Ghiselli and Kristján Örn Jóhannesson from the National University Hospital of Iceland for the medical image acquisition, Vicenzo Cangiano for his help in medical image segmentation. The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This study is part of the European project RESTORE ( https://restoreproject.eu/ ), funded by the European Union’s Horizon 2020 research and innovation program (grant agreement ID: 814558). This work has also been funded by Landspitalin Science fund (grant number: 960221). Publisher Copyright: © The Author(s) 2022. Publisher Copyright: © The Author(s) 2022.Objective: Assessment of human joint cartilage is a crucial tool to detect and diagnose pathological conditions. This exploratory study developed a workflow for 3D modeling of cartilage and bone based on multimodal imaging. New evaluation metrics were created and, a unique set of data was gathered from healthy controls and patients with clinically evaluated degeneration or trauma. Design: We present a novel methodology to evaluate knee bone and cartilage based on features extracted from magnetic resonance imaging (MRI) and computed tomography (CT) data. We developed patient specific 3D models of the tibial, femoral, and patellar bones and cartilages. Forty-seven subjects with a history of degenerative disease, traumatic events, or no symptoms or trauma (control group) were recruited in this study. Ninety-six different measurements were extracted from each knee, 78 2D and 18 3D measurements. We compare the sensitivity of different metrics to classify the cartilage condition and evaluate degeneration. Results: Selected features extracted show significant difference between the 3 groups. We created a cumulative index of bone properties that demonstrated the importance of bone condition to assess cartilage quality, obtaining the greatest sensitivity on femur within medial and femoropatellar compartments. We were able to classify degeneration with a maximum recall value of 95.9 where feature importance analysis showed a significant contribution of the 3D parameters. Conclusion: The present work demonstrates the potential for improving sensitivity in cartilage assessment. Indeed, current trends in cartilage research point toward improving treatments and therefore our contribution is a first step toward sensitive and personalized evaluation of cartilage condition.Peer reviewe

Rationale for prostaglandin I2 in bone marrow oedema – from theory to application

Introduction: Bone marrow oedema (BME) and avascular osteonecrosis (AVN) are disorders of unclear origin. Although there are numerous operative and non-operative treatments for AVN, pain management in patients with AVN remains challenging. Prostaglandins play an important role in inflammatory responses and cell differentiation. It is thought that prostaglandin I2 ([PGI2] or synonoma prostacyclin) and its analogues promote bone regeneration on a cellular or systemic level. The purpose of this study was to assess the curative and symptomatic efficacy of the prostacyclin analogue iloprost in BME and AVN patients. Method: We are reporting on 50 patients (117 bones) affected by BME/AVN who were treated with iloprost. Pain levels before, during and 3 and 6 months after iloprost application were evaluated by a visual analogue scale (VAS). The short form(SF)-36 health survey served to judge general health status before and after treatment. Harris Hip Score (HHS) and Knee Society Score (KSS) were performed as functional scores and MRI and X-rays before and 3 and 6 months after iloprost application served as objective parameters for morphological changes of the affected bones. Results: We found a significant improvement in pain, functional and radiological outcome in BME and early AVN stages after iloprost application, whereas patients with advanced AVN stages did not benefit from iloprost infusions. Mean pain level decreased from 5.26 (day 0) to 1.63 (6 months) and both HHS and KSS increased during follow-up. Moreover, the SF-36 increased from 353.2 (day 0) to 560.5 points (6 months). We found a significant decrease in BME on MRI scans after iloprost application. Conclusions: In addition to other drugs, iloprost may be an alternative substance which should be considered in the treatment of BME/AVN-associated pain

Doctor of Philosophy

dissertationIn Chapter 1, an introduction to basic principles or MRI is given, including the physical principles, basic pulse sequences, and basic hardware. Following the introduction, five different published and yet unpublished papers for improving the utility of MRI are shown. Chapter 2 discusses a small rodent imaging system that was developed for a clinical 3 T MRI scanner. The system integrated specialized radiofrequency (RF) coils with an insertable gradient, enabling 100 'm isotropic resolution imaging of the guinea pig cochlea in vivo, doubling the body gradient strength, slew rate, and contrast-to-noise ratio, and resulting in twice the signal-to-noise (SNR) when compared to the smallest conforming birdcage. Chapter 3 discusses a system using BOLD MRI to measure T2* and invasive fiberoptic probes to measure renal oxygenation (pO2). The significance of this experiment is that it demonstrated previously unknown physiological effects on pO2, such as breath-holds that had an immediate (<1 sec) pO2 decrease (~6 mmHg), and bladder pressure that had pO2 increases (~6 mmHg). Chapter 4 determined the correlation between indicators of renal health and renal fat content. The R2 correlation between renal fat content and eGFR, serum cystatin C, urine protein, and BMI was less than 0.03, with a sample size of ~100 subjects, suggesting that renal fat content will not be a useful indicator of renal health. Chapter 5 is a hardware and pulse sequence technique for acquiring multinuclear 1H and 23Na data within the same pulse sequence. Our system demonstrated a very simple, inexpensive solution to SMI and acquired both nuclei on two 23Na channels using external modifications, and is the first demonstration of radially acquired SMI. Chapter 6 discusses a composite sodium and proton breast array that demonstrated a 2-5x improvement in sodium SNR and similar proton SNR when compared to a large coil with a linear sodium and linear proton channel. This coil is unique in that sodium receive loops are typically built with at least twice the diameter so that they do not have similar SNR increases. The final chapter summarizes the previous chapters

Quantitative assessment of the biochemical composition of equine cartilage using 7T ultra-high field magnetic resonance imaging (MRI) techniques

No abstract available

Articular cartilage- and synoviocyte-binding small molecule drug delivery system for the intra-articular treatment of osteoarthritis

Intra-articular (IA) injection is an attractive route of administration for the treatment of osteoarthritis (OA). However, free drugs injected into the joint space are subjected to clearance mechanisms, which reduce their IA retention time. Additionally, several drug candidates can induce adverse off-target effects on different IA tissues. To overcome these limitations, tissue-binding, nano-composite microgels as IA small molecule drug delivery vehicles were designed. Micron-scale poly(ethylene glycol) (PEG) hydrogels, presenting cartilage- or synoviocyte-binding peptides and containing small molecule-loaded poly(lactic-co-glycolic) acid (PLGA) nanoparticles (NPs) were synthesized using microfluidics technology. Microgels loaded with a model small molecule (rhodamine B) exhibited a sustained, near-zero order release over 16 days. Additionally, PEG microgels functionalized with synoviocyte- or cartilage-targeting peptides, presented specific binding to rabbit and human synoviocytes, and to bovine articular cartilage in vitro, respectively. Using a rat model of knee OA, microgels were shown to be retained in the IA space for at least 3 weeks and did not induce detectable joint degenerative changes as measured by EPIC-μCT and histology. Finally, histological analysis demonstrated that synoviocyte-binding microgels were found trapped within the synovial membrane and significantly increased the IA retention time of a model small molecule near infra-red dye in vivo. Overall, these results suggest that nanocomposite PEG microgels presenting tissue binding peptides could be a promising strategy to achieve tissue-localized drug delivery and prolonged IA retention of small molecule drugs for OA treatment.Ph.D