The 2025 OARSI - Osteoarthritis Research Society International World Congress in Incheon, South Korea will be the first in Asia, bringing together the osteoarthritis research community from across the world. Chondrometrics GmbH and its representatives author numerous (n=13) abstracts on a wide range of topics submitted to OARSI 2025:

First Authorships:

FORWARD Study; Felix Eckstein et al.:
- Does treatment efficacy of intra-articular sprifermin on knee osteoarthritis differ between demographic strata - A post-hoc analysis from the FORWARD Phase 2 randomized controlled trial.

MECHSENS Study; Wolfgang Wirth et al.:
- Clinical validation of fully automated cartilage transverse relaxation time (T2) and thickness analysis using quantitative DESS MRI.

ROCELLA (Progress OA) Study; Felix Eckstein et al.:
- Effect of MRI-exclusions on recruitment failure and cartilage thickness change in a clinical trials of advanced knee osteoarthritis.

ROCELLA (Progress OA) Study; Wolfgang Wirth et al.:
- How sensitive are cross-vendor and vendor-specific deep-learning-based segmentation models to longitudinal change in cartilage thickness.

Co Authorships:

MECHSENS Study; Simon Herger et al.;
Univ. Hospital Basel, Switzerland:
- Two-year longitudinal changes in knee cartilage thickness and transverse relaxation time (T2) in ACL-injured versus healthy participants.

KANON Study; Staffan Larsson et al.;
Lund University, Sweden:
- Relationship between knee cartilage thickness and concentrations of biomarkers of matrix metabilism and joint specific inflammation after ACL injury - a longitudinal study.

IMI APPROACH Study; Frank Roemer et al.;
Boston Univ., USA & Univ. Erlangen-Nürnberg, Germany:
- Associations of patellofemoral structural damage with femorotibial cartilage loss over 24 months in Kellgren-Lawrence 2 & 3 knees.

IMI APPROACH Study; Eva Bax et al.;
Univ. Medical Center Utrecht, the Netherlands:
- Radiographic joint space width versus joint line convergence angle: Which one predicts cartilage thickness better?
- Impact of knee rotation on discrepancies between MRI cartilage thickness and mJSW discrepancies between MRI cartilage thickness and mJSW
- The Impact of varus and valgus alignment on knee cartilage quality assessed by MRI.

IMI APPROACH and OAI Study; Mylène Jansen et al.;
Univ. Medical Center Utrecht, the Netherlands
- Phenotyping knee osteoarthritis: comparing pain, liquid biomarkers and joint tissue pathology
- Spontaneous intrinsic cartilage thickening in osteoarthritic knees
- Topography of genuine sex-differences in femorotibial cartilage thickness

Big thanks to David Hunter and Milena Simic for a very warm welcome in Australia for my 1-month sabbatical, which took me to Sydney (NSW) to work with David & his group on mutual projects, concepts, & publications, then to Burleigh Heights (Queensland), for a National training and mentoring program for early-to-mid-career musculoskeletal researchers (MUSQ), then to Barossa Valley (South Australia) for the 2024 Conference on Quantitative Musculoskeletal Imaging, QMSKI, and finally to the Mornington Peninsula and Melbourne (Victoria) for meeting many colleagues and collaborators: SEE THE PICTORIAL ESSAY

It was a terrific start, heading with David straight from SYD airport to the Iceberg restaurant at Bondi, where meeting his daughter who was on shift that evening. To be followed by an enjoyable afternoon at with Milena Simic at Bondi Beach discussing our putative clinical trial and a systematic review paper on imaging studies of non-pharmacological, non-surgical interventions. On the weekend, some fine walks took us around Vaucluse, Nielsen Park, Shark Beach, Rose Bay, Dover Heights, Parsley Bay, the Gap, Watsons Bay & the Hornby Lighthouse. This was crowned by a fabulous kayak trip with David from Jenny's beach to Watson's beach, enjoying the first morning sunshine and the magic Sydney skyline.

 During the 1^st week I spent time at the University of Sydney, presenting on "Imaging Biomarker Qualification" and Imaging Endpoints in Osteoarthritis", first at the historic main campus and later the week at the Kolling Institute at Royal North Shore Hospital. I was trying to draw a perspective from the past to the latest achievements in participant selection for DMOAD trials, (multi-faceted) image acquistion protocols, (automated) image analysis methodologies, and the appropriate use of imaging endpoints, ideally to be qualified as surrogate outcomes for accelerated DMOAD approval. It was rewarding to meet so many established researchers and PhDs face to face, from David's and other groups in Sydney, all working on osteoarthritis, musculoskeletal imaging, and related topics. I also greatly enjoyed visiting the facilities, particularly the beautiful historic Anatomical Museum, Theater, and Dissection-Rooms. Another highlight was the walk from the Spit Bridge to Manly. Following the spectacular North Sydney Harbor coast and many beautiful bays, we eventually hit the famous “Bavarian” Restaurant at Manly wharf for a well-deserved lunch.

The 2^nd week was spent at Burleigh (Gold Cost, Queensland), with first class accommodation at the Hunter’s summer house. A big thanks to Kim Bennell (University of Melbourne), Paul Hodges (University of Queensland), and David for organizing an absolutely wonderful retreat, targeted at mid- and early-career researchers, with the venue taking place at Burleigh Heads Mowbray Park Surf Life Saving & Supporters Club. Invited presentations encompassed a range of clinical trial topics, including “Single to complex imaging endpoints in clinical trials” presented by myself. A lot of interesting short talks & pitches were also held by mid- and early-career investigators across various timely topics. Yet, Burleigh had more to offer than a acclimatized conference center at the beach. It definitely takes Australian discipline to stay in the sessions rather than rushing out to swim, surf, hike, run, bike, paddle-board, canoe, and whatever pleasant things can be done in this lush environment. It was a particular pleasure to meet with Ishanka Munugoda for a nice day trip to the close by National Parks, and to chat about everything that has happened since he worked with us in Salzburg as a visiting post-doc on an OARSI scholarship.

During my 3^rd week the QMSKI (Quantitative Musculoskeletal Imaging) workshop took place in Barossa, South Australia. This venue provides a unique format, bringing together those who research musculoskeletal tissues using the vast possibilities of modern (multi modal) imaging tools. With a focus on young investigators, novel technologies, and technical aspects of imaging, and with ample time for discussion, this 5-day event took place at the Novotel in a unique and secluded setting, where running away from the site simply was not an option. The approx. 100 participant meeting started with an accommodating welcome reception, to be followed by very well-organized research sessions, an exciting afternoon excursion to the nearby vineyards, and an awesome farewell party. See you all in beautiful “Island” where QMSKI 2026 will take place next.

The 4^th week came with a big variety of geographical highlights, starting with exploring Barossa a little bit deeper after the QMSKI workshop. Saturday was not a straight ride south, but one that looped through the backcountry and the beautiful Eden Valley, taking a familiar group of hitchhikers all the way to Adelaide. The city greeted us with beautiful exhibitions in its botanic gardens, and the so-called dumpling festival on its riverbanks, with lots of vibes and bites. The next day took me along the spectacular South Australian Pacific Coast, then further to the Victorian coastline, and finally along the Great Ocean Road. From there, and bypassing Melbourne, the ferry permits to cut right across the bay to the beautiful Mornington Peninsula, where I spent a lovely evening and next day with Kim Bennell, discussing eventful old (OARSI-Board) times as well as state-of-the-art study designs for OA clinical trials . Visiting Cape Schank lighthouse, the Mornington beach in the sunset, and the peninsula Hot Springs the day after left gorgeous impressions, before rendering visit to Flavia Cicuttini and her husband at their lovely home in Hawthorne. The next day was dedicated to meeting the team of Magellan Stem Cells Inc. at their impressive production site in Braesi, where we exchanged ideas and concepts about their phase 3 clinical trial that is about to be initiated with Julien Freitag (CMO), Michael Kenihan, Renee Castelluccio, Sara Shaba, David Petrie, and Peter Hansen. The weekend then passed quickly exploring the buzzling Melbourne city center and meeting new and old friends and colleagues: Ali Ghasem-Zadeh, Adam Culvenor, Ziru Wang, and Stefan Lohmander, stimulating interesting discussions and activities. The last evening's highlight was a visit to the Tina Turner musical currently performed in Melbourne, making a "grand finale" and farewell for the (long) way home.

We are proud to announce publication of our two first full original papers generated from OA-BIO, a €4.2 Million Eurostars grant awarded to a consortium of 4 partners: 4Moving Biotech, AO Research Institute Davos (ARI), Utrecht University, and Chondrometrics GmbH. The four-year project aims at developing life-changing therapy for osteoarthritis, using a biomarker-driven approach

The two papers published have just appeared in Skeletal Radiology and in Quantitative Imaging in Medicine and Surgery, two well-established journals in the field of Musculoskeletal Imaging:

1. Evaluation of an automated laminar cartilage T2 relaxation time analysis method in an early osteoarthritis model by Wolfgang Wirth et al.
   Skeletal Radiol 2024 Sep 4. Online ahead of print.
2. Clinical validation of fully automated laminar knee cartilage transverse relaxation time (T2) analysis in anterior cruciate ligament (ACL)-injured knees, by Felix Eckstein et al.
   Quantitative Imaging in Medicine and Surgery (QIMS) 2024: 14: 4319-4332.

These make use of two (human) models of early osteoarthritis that were already outlined in our 2020 "Year in review" (imaging) article in Osteoarthritis & Cartilage

The first publication relies on target knees withOUT radiographic osteoarthritis, but with contra-lateral knee radiographic joint space narrowing (JSN); the second one on patients with recent (anterior) cruciate ligament (ACL) injury. The overarching purpose was to technically and clinically validate an automated approach of cartilage MRI transverserelaxation time (T2) analysis.

In the two above papers we demonstrate that:

1. Cartilage segmentation by deep-learning (CNN- and U net-) based methodology applied to multiple echo spin echo (MESE) MRIs shows high agreement (DSCs) with expert reader segmentation
2. Automated analysis of T2 in the deep and superficialcartilage layer is accurate when compared with that derived from manual segmentations
3. Sensitivity to clinically important T2 differences or longitudinal T2 changes is similar between the automated vs. the traditional (expert manual segmentation) approach.

The automated analysis method is currently extended to its application in a quantitative dual echo steady state (qDESS sequence), a more efficient, high-resolution and rapid-acquisition 3D-MRI method for evaluating cartilage T2 (Paper). This ongoing work was recently presented at the International Workshop of Osteoarthritis Imaging (IWOAI) in Marrakech, Morocco, and it is currently submitted for full publication as an original paper.

We thank our co-authors: Susanne Maschek, Anna Wisser, Jana Eder, Christian Baumgartner, Akshay Chaudhari, Francis Berenbaum, Nicholas Brisson, and Georg Duda, and we thank the Chondrometrics expert readers for diligent cartilage segmentation: Jana Daimer, Gudrun Goldmann, Sabine Mühlsimer, Annette Thebis, and Barbara Wehr.

The MRI image analysis in the above studies was funded through OA BIO (E! 114932; Eurostars 2/ Horizon 2020) that supports early clinical development of 4P004, a putative first-in-class disease modifying osteoarthritis drug (DMOAD), as well as validation of osteoarthritis biomarkers required in its clinical development.

The stakeholders of the OA_BIO_CONSORTIUM (Eurostars) held their final project_meeting on September 16/17, 2024 in Freilassing, the location of Chondrometrics GmbH, one of its members.

In 2020, a 4.2 million € Eurostars grant had been awarded to the consortium, consisting of 4Moving Biotech, AO Research Institute Davos (ARI), Utrecht University, and Chondrometrics GmbH, with the aim to develop life-changing therapy for osteoarthritis following a biomarker-driven approach.

During the meeting, all parties presented the work performed during the past 4 years, and it was nice to see things come together. On behalf of Chondrometrics GmbH, Felix Eckstein presented on MRI acquisition, analysis, endpoints, and biomarker validation for clinical trials. Trials such as those 4Moving Biotech (4P-Pharma) are currently preparing for their i.a. compound liraglutide, which is intended to be submitted as a DMOAD (disease modifying osteoarthritis drug) to regulatory agencies.

But the meeting also focused on celebrating the strong friendship grown between the participants over the past years. Day 1 started with a Get together and lunch at the Chondrometrics GmbH office, and the actual meeting was then followed by a tour through rainy Salzburg. Dinner was taken at the famous Stiegl-Keller Salzburg, with the day rounded off by after dinner drinks at the CHM office. At the end of day 2, Osteria Lisa in Freilassing served their famous antipasti, before trains and airplanes had to be caught.

The participants also celebrated the installation of the OA BIO LinkedIn page that will showcase achievements made in the projects, with many publications yet to be finalized and published.

We thank all project partners for the great collaboration and hope to meet as often as possible in the future.

4Moving Biotech / 4P-Pharma:
Keren Bismuth, Jérôme Breton, Anne-Claire Gaudiez, Céline Martin, Coralie Meurot, Revital Rattenbach, Daniel López Sánchez, Lola Vigouroux Sautet

AO Research Institute Davos (ARI):
Eda Çiftci, Sibylle Grad, Mauro Alini, Zhen Li

Utrecht University:
Joost von Hegedus, Ann-Sofie Scheike, Marianna Tryfonidou

Also, thanks so much to 4P-Pharma for the very kind invitation to their 10th Anniversary and for the fantastic “Best of” video about this remarkable event, which is a must see: OA Best Of de la soirée du dixième anniversaire de 4P-Pharma

September 19th was a magic evening amongst great friends and dear colleagues, cruising Paris along the Seine on the boat used by the French "equippe" for the opening of the Olympics 2024.

We are proud that two related original papers from the FORWARD study have now been fully published. These provide valuable information for further developing intra-articular sprifermin as a disease modifying osteoarthritis drug (DMOAD).

The first on: “Is detection of disease-modifying osteoarthritis drug treatment more effective when performing cartilage morphometry without blinding to MR image acquisition order?” has been published in Osteoarthritis Cartilage 2024 Oct;32(10):1346-1351 (https://pubmed.ncbi.nlm.nih.gov/38844160/) addresses the so far unanswered question, whether in osteoarthritis we should - as often done in other disease areas - analyze (MR) images unblinded rather than blinded to the relative temporal order of imaging acquisition, when trying to detect longitudinal change and treatment effects on articular structures. It has been theorized that a potential treatment effect may be discovered with greater sensitivity when employing unblinded analysis, but the potential drawback is a bias in estimating accurate rates of change over time, if of interest. Answering this question has taken so long because there were no trials with a structural treatment effect were available to test it.  

The second one: “Unbiased analysis of kneeartilage thickness change over three years after sprifermin vs. placebo treatment - A post hoc analysis from the phase2B FORWARD study” has been published in Osteoarthr Cartil Open 2024 Aug 23;6(4):100513: https://pubmed.ncbi.nlm.nih.gov/39286575/

Thanks to the OARSI Communications Committee members Jamie Collins and Shi Cong Tao for including this article into this month's selection of the most relevant publications in the field (Oct 3rd, OARSI News).

FORWARD was the first randomized controlled trial evaluating post treatment benefits of a potential disease modifying osteoarthritis drug (DMOAD). The total observation time of this RCT was 5years (Y), 2Y during, and 3Y post treatment https://pubmed.ncbi.nlm.nih.gov/33962962/ In this post hoc study, we re-analyzed the previously published FORWARD MRI data, but with blinding the post-treatment cartilage thickness readings ((Y2 vs. Y5) to the temporal order of acquisition (blinded & unbiased analysis). This is relevant, because reading MRIs blinded vs. unblinded to acquisition order significantly affects the observed longitudinal rate of cartilage thickness change https://pubmed.ncbi.nlm.nih.gov/38844160/

Conducting an unbiased (blinded) cartilage analysis, we here find that cartilage thickness gained with 100μg sprifermin treatment up to Y2 is maintained up to Y5 compared with placebo. From this observation we infer that the cartilage accumulated during the anabolic treatment is structurally viable, mechanically competent, and sustainable, and able to withstand the mechanical environment similar to non-Sprifermin-treated osteoarthritic cartilage. Cartilage loss has been prospectively related to joint death (knee replacement) as the final clinical endpoint of knee OA. It is hence conceivable that maintenance of (anabolic) structural benefit is pivotal in achieving translation of structural benefit (i.e. increased cartilage thickness) to symptomatic improvement.

These findings strengthen the requirement to continue DMOAD trials beyond the actual treatment period, and to assess - in blinded and unbiased manner - to what extent structural treatment effect size is maintained post-treatment and eventually translates into clinical benefit.  

We are proud to announce our design and MRI acquisition protocol paper in Osteoarthritis Cartilage Open 2024 Jul 23;6(3):100505. PMID: 39183946  

Design of a sample rapid MRI acquisition protocol, supporting the assessment of multiple articular tissues & pathologies in knee osteoarthritis. by Felix Eckstein et al.

In this expert opinion paper, we describe and discuss a <30 min MRI acquisition protocol for use in interventional clinical trials. This will be applied in the PROTO Horizon EU-consortium project (one for a rehabilitation, and one for an i.a. therapy study), as a basis for (automated) image segmentation and analysis of multiple (quantitative) endpoints.

 The intent was to be both visionary and realistic, in that all sequences can be installed and used on a clinical (3T) scanner, but are not yet routinely applied for the given purpose. The spearhead is a qDESS (double echo steady stated) water excitation (we) sequence originally proposed by Akshay Chaudhari and others https://pubmed.ncbi.nlm.nih.gov/29090500/ (Fig. top row). The sequence is unique in that it permits analysis of quantitative endpoints of all below measures:

• cartilage morphometry (e.g. cartilage thickness, subchondral bone & denuded area)
• cartilage T2 (transverse relaxation time, related to collagen & hydration)
• bone shape, including complex measures such as the B-score
• meniscus morphology and position (coverage, overlap, extrusion)
• potentially also Hoffa synovitis

Although qDESS is not routinely available on clinical scanners, it can be installed with the help of dedicated application specialists under a research agreement with the manufacturer, once fitted to the specific soft- and hardware environment.

We further suggest “clinical” IW TSE FS acquisitions in 3 planes to support radiological scoring of structural pathologies (cartilage, meniscus, and bone marrow lesions, Hoffa- and Effusion synovitis, bone pathology, Fig.).

Finally, we propose a FLAIR sequence (Fig. bottom right), because of its superiority in separating synovitis from effusion compared with IW TSE FS (Fig.). As indiated above, qDESS may have some potential in detecting Hoffa synovitis. These two sequences hence represent interesting options, if contrast enhanced (CE) MRI is not available or not recommended for a trial (see PROTO), albeit clearly representing the gold standard in the assessment of synovitis. Synovitis represents a core topic in the PROTO Horizon project, with quantitative non-CE MRI endpoints of synovitis being developed and tested.

This work is funded by the European Union / Grant Agreement Nr. 101095635 (PROTO-Horizon Europe). Views and opinions expressed are those of the authors and not of the EU, with neither the EU nor the granting authority to be held responsible. The design of the image acquisition protocol and the content of this article has not been contingent upon approval from the sponsor.

From July 26-28, 2024, Chondrometrics GmbH held it's annual training retreat as a Summer Camp in Ainring.

On Friday evening, Scientific Advisory Board (SAB) member Rainer Burgkart shared exciting insights on the functionality, utility & future developments of ChatGPT, as a versatile research tool in science and daily life. The presentation stimulated lively discussions around our future life with artificial intelligence (AI).

On Saturday, the team recapitulated the status of current & future projects, the pipeline of clinical trials gladly being nicely filled for the fore-seeable future. Quality management (QM) and Good Clinical Practice (GCP) were on the agenda, with updates on implementation provided.

Saturday afternoon was dedicated to climbing Mt. Teissenberg, to take a break @ Stoißeralm with its splendid views, and later by cooling down and having a nice swim @ Lake Höglwörth. The Kloster beergarden near the lake provided further delights and piece of mind.

Finally, Sunday will be dedicated to summarizing the scientific achievements made by Chondrometrics over the past year, covering confererence contributions, review articles, and original papers.

Further, the team was given a "tour" to the new Chondrometrics Webpage and LinkedIn page, as well as a summary of statistics of its usage.

We are excited that following a call for a Special Issue on sex differences in osteoarthritis:
https://www.sciencedirect.com/special-issue/10VMS3T8C3L with guest editors Dieuwke Schiphof (Erasmus, Rotterdam) and Tristan Maerz (University of Michigan), our two review articles on the anatomical and imaging aspects of this topic (i.e. morpho-types) are now published.

READ on sex-differences in radiographic joint space width (JSW), meniscus & ligaments, cartilage morphology, composition & deformation, and articular tissue response to treatment in the review on articular tissue anatomy in the Special Issue OAC: https://pubmed.ncbi.nlm.nih.gov/38871022/

…and then on bone size & shape, subchondral & subarticular bone, synovial membrane & infra-patellar fad-pad (IPFP), muscle & adipose tissue, and eventually peri-articular tissue response to treatment in the the second review on peri-articular tissue anatomy in OAC OPEN:  https://pubmed.ncbi.nlm.nih.gov/38946793/

• Did you know that humans exhibit greater evolutionary homogeneity than most other species, since their genetic repertoire originates from a small population of <1500 breeding individuals, a “bottleneck” in evolution that lasted >100.000 years, bringing human ancestors close to extinction?
• As authors, we are aware that classifications of human sex cannot be reduced to female/male. However, given lack of literature on non-binary individuals, this review article is limited to the analysis of sexual dimorphism, "morpho-types" around which variability clusters.
• Women demonstrate more severe manifestations of musculoskeletal disorders, the inter-sex-disparity increasing with age. Knee and hand osteoarthritis are more prevalent in women, particularly symptomatic osteoarthritis.
• It remains currently enigmatic to what extent sex-differences in osteoarthritis incidence originate from sexual dimorphism in joint anatomy, potentially exposing women to greater vulnerability.

From reviewing the literature, we conclude that female joints may be anatomically (and biomechanically) disadvantaged and at greater risk of incident knee osteoarthritis.

We reproach that only few publications mention the term “sex” in their title or abstract, data mostly “hidden” in the results.

Sex should not only be treated as a confounder, but statistical analysis should be undertaken in sex-specific strata. Sex-comparison is often confounded by demographic or disease factors.

Only few papers reported sex-differences in structure modifying interventions, this unfortunately not being the standard in clinical trials.

Sex-specific healthy reference data, and public data bases of (peri-) articular tissue properties at various developmental stages are lacking and urgently needed for comparison

The “one_size|sex fits_all” approach must be abandoned in scientific reporting. Differences between women, men, and otherwise categorized individuals must be recognized, in research as well as in clinical practice.

This approach should be pursued per self-commitment of the scientific-community, and adopted into official editorial policies of scientific journals and text books for full implementation.

We are tremendously grateful to the many colleagues who supported us in identifying and reporting these data:

Article 1 (OAC Special Issue): Gerard Ateshian, Francis Berenbaum, Flavia Cicuttini, Martin Englund, Ali Guermazi, David Hunter, Mylène Jansen, Gabby Joseph, Thomas Link, Malcolm Logan, Michael Nevitt, Frank Roemer

Article 2 (OAC OPEN): Kim Bennell, Francis Berenbaum, Mikael Boesen, Alan Brett, Ali Guermazi, David Hunter, Gabby Joseph, Olga Kubassova, Virginia Kraus, Thomas Link, Steve Messier, Ralph Mueller, Michael Nevitt, Andrew Pitsillides, Frank Roemer, Kathryn Stok

We spent 4 rich and intense days at the 2024 International Workshop of Osteoarthritis Imaging (18th IWOAI) in Marrakech, Morocco, with enlightening lectures on the relationship between pain and structure in osteoarthritis. There was great opportunity to establish new contacts and nurturing existing friendship amongst researchers from academia and industry, hopefully soon bringing the first and long-awaited disease modifying osteoarthritis drug (DMOAD) to market.

Felix Eckstein with Jamie Collins were invited to speak about multi-component and composite outcomes vs. single endpoints tailored to the specific mechanism of action (MOA) in putative DMOAD trials. This will be followed by a “Perspective” on this topic in the “Osteoarthritis Imaging” Journal (OSTIMA) and will be hopefully available for reading soon.

Wolfgang Wirth presented on the clinical validation of cartilage transverse relaxation time by MRI (T2), known to be related to cartilage composition and mechanical properties. Segmentation was performed using new fully automated convolutional-neural-network (CNN)-based models, and a novel high-resolution qDESS MRI sequence. The study was conducted in close collaboration with Annegret Mündermann and Simon Herger from the University of Basel, Switzerland. It was found that knees with anterior cruciate ligament (ACL) injury exhibit longer T2 (suggesting early cartilage pathology) in the deep femorotibial cartilage compared with contra-lateral knees or healthy reference knees. The superficial cartilage T2 and the cartilage thickness, in contrast, were not significantly different between case and reference knees. This work was supported by a Eurostars OA-BIO consortium grant and represents a big step forward in achieving time- and cost-efficient analysis of cartilage T2 and thickness from the same image acquisition (qDESS) and (automated) segmentation algorithm.

Anna Wisser displayed a poster on a rapid (<30 min) sample acquisition protocol, encompassing MRI sequences for (quantitatively) assessing synovitis (no contrast), cartilage thickness and cartilage T2, and (semi-quantitative scored) structural pathologies of articular tissue. This first study in the PROTO Horizon project was co-authored by Chondrometrics GmbH team members and Nicholas Brisson, Georg Duda, Tazio Maleike, and project head Tobias Winkler from the Universitätsmedizin Berlin.

Susanne Maschek presented a poster on sexual dimorphism of radiographic joint space width (JSW) in joint space narrowing (JSN) strata of almost 1000 subjects. Med higher values of greater JSW than women, but the difference decreased with greater JSN. She further assessed "genuine" sex differences in femorotibial cartilage thickness, independent of other demographic factors. Women matched for the same body height-, age-, and BMI and without radiographic disease values than women still displayed approx. 10% less cartilage thickness and also smaller joint surface areas, indicating that women may be structurally disadvantaged in terms of suffering from knee osteoarthritis (for the poster, please see the OARSI 2024 NEWs section)

Felix Eckstein eventually compared the performance of coronal FLASH and sagittal DESS MRI in discriminating progressor vs. non-progressor knees in the OAI FNIH Biomarker sample (FNIH1), using fully automated segmentation of cartilage thickness. Co-authored by Wolfgang Wirth from Chondrometrics, Akshay Chaudhari (Standford University) and David Hunter (University of Sydney), the novely of that study is that the comparison is without potential reader preference or bias, given that the analysis was done fully automated using a CNN-based deep learning AI algorithm that was trained on the FLASH and DESS images of a different set of knees. The study reported greater rates of progression by FLASH than DESS, but also greater standard deviations and progression in control subjects, so that the actual discrimination of both groups was very similar across both MRI sequences

Impressions from Marrakesh

Ali Guermazi, MD, PhD Guermazi is to be hugely thanked for organizing a fantastic conference and venue that kept us without sleep not only for the day but also for most of the nights. We all look forward to meet in Cambridge for the 19th IWOAI hosted by Tom Turmezei in July 2025.

EULAR Announcement

The “European Alliance of Associations for Rheumatology” (EULAR) is one of the largest organizations of its kind worldwide, and holds one of the largest research conferences in rheumatoid and osteoarthritis. This year, the conference takes place from June 12-15 in beautiful Vienna, with more than 18,000 participants from over 130 countries expected to attend EULAR Congress.

Two weeks from now (Friday, June 14, at 12:00 CEST), we will - with our esteemed colleagues from Formation Bio, NBCD, and CHL4special consulting - present a poster titled: “Unbiased Analysis of Knee Cartilage Thickness Change Over Three Years Post-Treatment with Sprifermin vs. Placebo – A Post-Hoc Analysis from the Phase II FORWARD Study”. #POS1083 will be displayed during the Poster Tour: “Clinical Studies in Osteoarthritis” (Room Poster View / Session VI).

Figure showing the quantitative change in cartilage thickness by MRI morphometry in the (total) femorotibial joint (TFTJ) during the treatment phase (baseline to Y2), and during the post-treatment period (Y2 to Y5). The readers were blinded to the relative temporal order of the MRIs for both periods: q12 = drug injected i.a. every 12 months, and q6 = every 6 months (up to 18 months), at dosages of 30 µg or 100 µg, respectively.

The FORWARD study (NCT01919164) is one of the first placebo controlled, randomized control trials (RCTs) that have clearly demonstrates an anabolic effect of a drug (Sprifermin) on joint structure in knee osteoarthritis, specifically cartilage thickness by magnetic resonance imaging (MRI). And the first to include an extensive follow-up period of 3 years (Y) after a 2Y treatment period (Fig.). For a summary and “download area” of original publications related to Sprifermin, please visit the research section of our Webpage: Sprifermin Summaries > Exclusive Executive Summaries > The Sprifermin Program.

At EULAR 2024, we will present an unbiased analysis of the FORWARD post-treatment MRI data on articular cartilage thickness change, measured using quantitative morphometry by Chondrometrics 3.0 software. Expert readers were blinded to the temporal order of the MRI acquisitions acquired at Y2 and Y5. Our results demonstrate that the rates of cartilage thickness loss (slopes) during this period do not differ significantly between placebo and the various sprifermin dose groups (Fig.). Further, the difference in cartilage thickness seen at Y2 between sprifermin-treated participants and placebo is fully maintained up to Y5 (Fig.). The additional sprifermin-induced cartilage tissue present at the end of the treatment period is hence not lost at greater rates post-treatment than “normal” osteoarthritic cartilage of placebo participants. This supports the interpretation that cartilage tissue gained during anabolic treatment is biologically viable and mechanically competent post-treatment, warranting sustainable structural treatment effects on knee osteoarthritis for several years.

Join us on Friday, June 14, 2024, noon, for more data and lively discussions.

The team of Chondrometrics GmbH and the Research Program for Imaging at Paracelsus Medizinische Privatuniversität presenting at the World Congress in Vienna included Susanne Maschek (Chief of Human Resources and Quality Control), Anna Wisser (Project Manager), Wolfgang Wirth (Chief Technical Officer and Chief of Quality Control), Clemens Heistracher (PhD Student), and Felix Eckstein (CEO & CMO). Felix Eckstein gave an Oral Presentation during the Imaging Session on Friday, April 19^th (No. 20) on the impact of unblinded reading vs. segmentations blinded to the order (time point) of image acquisition on the rates of longitudinal cartilage thickness change, and on the structural treatment effects on cartilage in osteoarthritis.
During the China-Germany-Night later the same day, he gave a Review Lecture on the role of imaging biomarkers in the development of disease modifying osteoarthritis drugs (DMOADs), on current disease-modifying treatment trials in osteoarthritis, and on recent results obtained with fully automated segmentation & analysis of articular tissues, using AI- (more specifically CNN-) based algorithms.
The group presented 6 first-author posters, and co-authored another 4 posters with their collaborating partners, all displayed below. The 10 posters cover a wide range of imaging applications in osteoarthritis research and nicely reflect the current status of work both at Chondrometrics and at the group at PMU.
We hope seeing you again at OARSI 2025 next April in Seoul, Korea.
Finally we would like to thank the below researchers for their invaluable contributions and the exciting collaborations:

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First-author posters

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Co-author posters

From Chondrometrics Headquarters in Freilassing to Messe Wien is a 350 km journey that typically takes around 3 ½ hours by car. However, by following the course of the 4 rivers Saalach, Salzach, Inn, and Donau (Danube), the distance extends to 450 km, requiring approximately 24 hours on a bicycle.
David Hunter from the University of Sydney and Felix Eckstein opted for the scenic route to the @OARSI Conference 2024, using the extended travel time to rejuvenate mind and body while enjoying informal discussions and camaraderie. Their expedition commenced from Freilassing to Burghausen on the first day, where the world's longest castle stands.

On the second day, they reached Passau, where the convergence of the Inn, Danube, and Ilz rivers often floods the historic town.  

Continuing on the third day, they arrived in Linz, renowned for its blend of industry and artistry.

The fourth day began with a hearty breakfast at the delightful Kaiser’s K&KBakery and concluded in the historic town of Ybbs after covering a modest 80 kilometers due to somewhat inclement weather.  

The following morning, both cyclists were greeted by the impressive Monastery of Melk, heralding their entry into the picturesque wine region of the Wachau. From the avant-garde town of Krems, they had to board a train to Wien-Heiligenstatt to ensure they stayed on schedule for their initial appointments in Vienna. Nonetheless, they still enjoyed a memorable "entrance" into Vienna by crossing the Danube_Island. Their legs and spirits alike rejoiced upon their arrival at Vienna / Prater, where an engaging OARSI conference awaited, promising to keep them occupied and inspired for the days ahead.

Scientists from Chondrometrics and PMU will be delivering an oral presentation and several posters on quantitative measurement methodology of articular tissue pathology, as featured in this post.

The OARSI World Congress is the largest global platform of those engaged in osteoarthritis (OA) research. It attracts professionals from diverse disciplines in academia & industry, basic, translational and clinical scientists, allied health professionals, and policy makers. This year, the congress is held at Messe Wien Congress Center, and anticipates attracting >1,000 attendees from >40 countries. OARSI, the Osteoarthritis Research Society International, is the premier society to advance the understanding and treatment of OA, a debilitating condition affecting >600 million people worldwide.

Felix Eckstein, Research Professor at Paracelsus Medical University (PMU, Salzburg, Austria), and CEO of Chondrometrics GmbH (Freilassing, Germany) has recently become the Austrian National Ambassador for OARSI. He enthusiastically anticipates the World Congress to be hosted in the country of his academic work, his research group being affiliated with the Ludwig Boltzmann Institute of Arthritis and Rehabilitation (LBIAR) under leadership of Tanja Stamm.

On Friday, April 19 (8:45-10:15, Abstract No. 020) he will give a talk supported by a team from Formation Bio, owner of a potentially disease-modifying OA drug: “Sprifermin”. The presentation will focus on whether analyzing magnetic resonance images (MRIs) without blinding to relative acquisition order affects observed effect sizes of drug efficacy on cartilage thickness in the FORWARD trial. He will also present a poster (No 90) on the clinical validation of fully automated measurement of cartilage composition using MRI (T2), employing deep learning (AI). This work involves researchers from Charité (Nicholas Brisson & Georg Duda) and 4P Pharma (Francis Berenbaum) and is part of both the OVERLOAD and OA-BIO Eurostars project.

Susanne Maschek, Chief of Education and Quality Control at CHM, will present a poster (No 492) on the impact of MRI scanner field strength on cartilage T2. The study includes a low-field magnet (0.55 Tesla) suitable for outpatient settings, clinical ( 1.5 and 3.0T), and a high-field research scanner (7.0T). The work was performed in collaboration with Frank Roemer's group at the University of Erlangen and representatives of Siemens Healthcare.

Anna Wisser, Project Manager at PMU and CHM, will present a poster (No 207) on whether diabetes mellitus affects physical function and thigh muscle strength in participants of the Osteoarthritis Initiative. The study is part of a broader project exploring the impact of blood surgar on tissue structure and pathology in OA within the LBIAR.

Clement Heistracher, PhD candidate of Jana Eder at PMU will contribute a poster (No 084) on fully unsupervised automated segmentation of muscle and adipose tissue of thigh MRIs. Automated segmentation is performed without labeled data, providing a substantial advance in automated image segmentation technology.

Wolfgang Wirth, Senior Postdoc at PMU and Chief Technology Officer at CHM, will present a poster (No 491) on fully automated segmentation, comparing the ability of different MRI sequences in detecting OA cartilage thickness change, with co-authors Akshay Chaudhari from Stanford University and David Hunter from the University of Sydney. A second poster (No 493) explores the magnitude of sex-differences in radiographic knee joint space width (JSW), a commonly used measure of OA status and progression. It further studies "genuine" sexual dimorphism in JSW and cartilage morphometric measuring, comparing female and male Osteoarthritis Initiative participants with the same body height. The poster is part of a broader initiative to characterize sex differences in (peri-) articular tissues as potential risk factors for knee OA, currently submitted to a special issue of the Journal of Osteoarthritis & Cartilage.

It is with great pleasure and a bit of pride to see our review on 30 years of MRI-based cartilage and bone morphometry in knee osteoarthritis published in the special issue of Osteoarthritis and Cartilage Journal.

This exciting journey has taken us from initial “correlation”, i.e. method development with external reference standards for validation to exploring the physiology and pathophysiology of the disease, to qualification studies towards a surrogate endpoint, and finally to interventional “clinical trials”, exploring the structural efficacy of potentially disease modifying OA drugs (DMOADs) on articular tissues.

It has been a great fortune to be able to work on this review with our co-authors from Monash University in Melbourne (Australia): Anita Wluka and Flavia Cicuttini, and receive support of esteemed colleagues, namely Mylène Jansen (Universitair Medisch Centrum Utrecht), Alan Brett (Stryker - Imorphics) and Christoph Ladel (CHL4special consulting).

We are grateful for all the support we received and hope you enjoy reading the article

Felix Eckstein, Wolfgang Wirth
LinkedIn

Despite Lufthansa strikes causing turbulence with arrivals, everyone eventually reached Freilassing safely, albeit with some delays. Neal Bangerter (Imperial College), Mikael Boesen (University of Copenhagen), Akshay Chaudhari (Stanford University), Chris Ladel (4Consulting Darmstadt), and Ali Mobasheri (University of Oulu) turned out to be an incredibly productive and inspiring group. 

Topics for discussion included state-of-the-art and future MRI sequences, automated tissue segmentation using AI- and deep-learning based methods, quantitative methodology for analysis of synovitis, set-up of an “ideal” clinical trial for structure modification in osteoarthritis, and the acceptance of automated measurement methodology and imaging assessments as surrogate endpoints by regulatory agencies. Yet, as in former years, the group was also a lot of fun and enjoyed good company, friendship, restaurants, and great skiing at Leogang, Kitzbühl, and Fieberbrunn ski stations. Something to be certainly repeated.

The team of Chondrometrics GmbH and the Research Program for Imaging at Paracelsus Medical University presenting at the Imaging Workshop in Lausanne included Susanne Maschek (Chief of Human Resources and Quality Control), Anna Wisser (Project Manager & PhD), Wolfgang Wirth (Chief Technical Officer and Chief of Quality Control), and Felix Eckstein (CEO & CMO).

The group contributed 3 first author oral presentations and 2 posters displayed below. Susanne Maschek spoke on the variability of cartilage T2 measurements between MRI field strengths ranging from 0.55 to 7.0 Tesla, Wolfgang Wirth on the imaging characteristics of 3 different osteoarthritis endotypes derived from liquid (biochemical) markers, and Felix Eckstein on the agreement of laminar (deep and superficial) T2 between fully automated and expert manual analysis. Anna Wisser presented a poster on the agreement of automated vs. manual T2 analysis in radiographically normal knees with and without MRI cartilage lesions, and Felix Eckstein one on cartilage T2 in anterior cruciate ligament (ACL) injured patients (non-copers, copers, and operated) vs. healthy controls.

We thank our co-authors for the great collaboration on the above projects, and we look forward seeing you at the OARSI World Congress 2024 in April in Vienna as well as at the IWOAI 2024 in June in Marrakech.

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First-author posters

Chondrometrics was founded in Munich, Germany in April 2004, by Prof. Reinhard Putz and PD Felix Eckstein. What was initially thought to be an investment for a single project, turned out to be a >20 year success story that will hopefully continue for many more years. Thanks to wonderful colleagues and employees, the small University group, with initial experience in cartilage segmentation, emerged to a leading vendor of medial image analysis. Today, Chondrometrics participates in many important clinical trials of disease modifying osteoarthritis drugs (DMOADs), using its ISO 13485 approved quality management system and it’s under the current MDR “CE” approved software platform.

Big reason to celebrate! On April 22^nd/23^rd, two weeks after the actual date, the Chondrometrics team joined in Freilassing, the site of the new office. Although officially the location business since 2021, the 20^th anniversary gathering also marked official inauguration of the premises. 

The team was joined by Prof. Reinhard Putz and former team members Jana Eder (geb. Kemnitz), Manuela Kunz, Jan Hohe, Tobias Stammberger, and David Fuerst. After “aperitivo” at the office, the party spent a nice Bavarian evening at the Zollhäusl, marking the close border to Austria, and then went hiking on the next day to the Hochschwarzeck, where lunch was taken in the sunshine with a splendid view onto the mountain peaks of the Chiemgau.

Plans are already being made for the 25^th anniversary, in April 2028

The team of Chondrometrics GmbH and the Research Program for Imaging at Paracelsus Medizinische Privatuniversität presenting at the World Congress in Denver included  Wolfgang Wirth (Chief Technical Officer and Chief of Quality Control), Anna Wisser (Project Manager), Kalpana Sharma (PhD student), and Felix Eckstein (CEO & CMO).
The group presented the 5 first-author posters displayed below. These reflect the current project status at Chondrometrics and at PMU. They cover topics ranging from Imaging-based characterization of osteoarthritis endotypes (APPROACH project), the relationship of meniscus extrusion with structural and symptomatic osteoarthritis progression (OAI FNIH 1 Biomarker Consortium project), the clinical validation of automated (U-net-based) cartilage T2 analysis using two different clinical models (Eurostars OA BIO project), and finally a project studying whether automated cartilage thickness analysis profits from quality control and correction compared with manual gold standard segmentations.

We would like to thank our many collaborators for their support and contribution to the above projects, and it will be a pleasure seeing you all at the 2023 Imaging Workshop in Lausanne

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First-author posters