Why radiography should no longer be considered a surrogate outcome measure for longitudinal assessment of cartilage in knee osteoarthritis

Imaging of cartilage has traditionally been achieved indirectly with conventional radiography. Loss of joint space width, or 'joint space narrowing', is considered a surrogate marker for cartilage thinning. However, radiography is severely limited by its inability to visualize cartilage, the difficulty of ascertaining the optimum and reproducible positioning of the joint in serial assessments, and the difficulty of grading joint space narrowing visually. With the availability of advanced magnetic resonance imaging (MRI) scanners, new pulse sequences, and imaging techniques, direct visualization of cartilage has become possible. MRI enables visualization not only of cartilage but also of other important features of osteoarthritis simultaneously. 'Pre-radiographic' cartilage changes depicted by MRI can be measured reliably by a semiquantitative or quantitative approach. MRI enables accurate measurement of longitudinal changes in quantitative cartilage morphology in knee osteoarthritis. Moreover, compositional MRI allows imaging of 'pre-morphologic' changes (that is, visualization of subtle intrasubstance matrix changes before any obvious morphologic alterations occur). Detection of joint space narrowing on radiography seems outdated now that it is possible to directly visualize morphologic and pre-morphologic changes of cartilage by using conventional as well as complex MRI techniques

The Health and Structural Consequences of Acute Knee Injuries Involving Rupture of the Anterior Cruciate Ligament

Although there is an abundance of literature regarding the development of knee osteoarthritis after rupture of the anterior cruciate ligament (ACL), the mechanism underlying this link is not clear. Recent studies have reported that several factors may be predictive of the development of osteoarthritis, including damage to the menisci and articular cartilage during the initial trauma, altered knee biomechanics after injury, and episodic instability. This article summarizes recent developments in the understanding of the joint damage resulting from an ACL tear, and the influence that current and future treatment methods may have on the long-term progression to osteoarthritis

Standardized multi-vendor compositional MRI of knee cartilage: A key step towards clinical translation?

Cartilage compositional magnetic resonance imaging (MRI) techniques are sensitive to changes in the composition of the extracellular matrix of articular cartilage. Their promise lies in the potential to detect the earliest stages of cartilage degeneration, at a stage where these changes may still be reversible. This is a considerable advantage over conventional (structural) MRI; even with the high spatial-resolution imaging offered by modern high-field (3T) MRI systems, by the time structural cartilage damage is apparent, there is (by definition) damage to the collagen matrix implying that the changes are probably already irreversible

Imaging of Osteoarthritis

Osteoarthritis (OA) is the most prevalent joint disorder in the elderly, and there is no effective treatment. Imaging is essential for evaluating the synovial joint structures (including cartilage, meniscus, subchondral bone marrow and synovium) for diagnosis, prognosis, and follow-up. This article describes the roles and limitations of both conventional radiography and magnetic resonance (MR) imaging, and considers the use of other modalities (eg, ultrasonography, nuclear medicine, computed tomography [CT], and CT/MR arthrography) in clinical practice and OA research. The emphasis throughout is on OA of the knee. This article emphasizes research developments and literature evidence published since 2008

Longitudinal assessment of cyst-like lesions of the knee and their relation to radiographic osteoarthritis and MRI-detected effusion and synovitis in patients with knee pain

Introduction\ud The purpose of the present study was to determine the prevalence of cystic lesions and cyst-like bursitides in subjects with frequent knee pain and to assess their relation to radiographic osteoarthritis (OA) severity; to describe bilaterality and size fluctuation of the lesions over 6 months; and to assess relations between the prevalence of synovium-lined lesions communicating with the joint capsule and severity of magnetic resonance imaging (MRI)-detected effusion and synovitis.\ud \ud Methods\ud One hundred and sixty-three subjects (total 319 knees) aged 35 to 65 with chronic, frequent knee pain were included. Imaging with 3 Tesla MRI was performed at baseline and 6-month follow-up with the same protocols as those used in the Osteoarthritis Initiative. Severity of radiographic OA was assessed using the Kellgren-Lawrence grade (0 to 4). Severity of effusion and synovitis was graded 0 to 3 based on the Whole Organ Magnetic Resonance Imaging Score system. The associations of cysts and cyst-like bursitides and severity of radiographic OA, MRI-detected effusion and synovitis were analyzed using logistic regression controlling for clustering by person. The Wilcoxon signed-rank test was used to determine whether there was a significant change in the size of lesions between baseline and follow-up.\ud \ud Results\ud At least one lesion (any type) was present in 222 (70%) knees. The most prevalent lesions were popliteal cysts (40%, 128/319), followed by subgastrocnemius bursitis (15%, 49/319) and proximal tibiofibular joint cysts (8%, 26/319). Bilateral lesions were seen in 49% of the subjects. Only popliteal cysts and subgastrocnemius bursitis showed a significant change in size (P < 0.001). No trend was observed between prevalence of any of the cyst-like lesions analyzed and the increasing radiographic OA severity. Increasing prevalence of subgastrocnemius bursitis was associated with increasing severity of effusion (P = 0.0072) and synovitis (P = 0.0033).\ud \ud Conclusions\ud None of the cyst-like lesions analyzed seems to be a marker of radiographic OA severity in knees with chronic frequent pain. Subgastrocnemius bursitis may be used as a marker of effusion/synovitis severity. Bilateral cyst-like lesions are relatively commonly observed in people with chronic knee pain

Phenotypic characterization of skeletal abnormalities of Osteopotentia mutant mice by micro-CT: a descriptive approach with emphasis on reconstruction techniques

PurposeThe novel protein osteopotentia (Opt) has recently been described as an essential regulator of postnatal osteoblast maturation and might possibly be responsible for some of the rarer types of osteogenesis imperfecta. Our aim was the evaluation of micro CT for the qualitative morphological assessment of skeletal abnormalities of Osteopotentia-mutant mice in comparison to radiography and histology.Materials and methodsFour homozygous mice with insertional mutations in the Opt gene and three wild-type controls were examined ex vivo using radiography and micro-CT. Two of the homozygous animals were evaluated histologically (trichrome reagent). For the micro-CT evaluation three-dimensional (3D) surface reconstructions and two-dimensional (2D) multiplanar reformations (MPRs) were applied.ResultsThe Opt-homozygous mice exhibited severe growth. The radiographic examinations showed osteopenia and fractures with hypertrophic callus formation and pseudarthroses of the forelimbs and ribs. Micro-CT confirmed these findings and was able to demonstrate additional fractures especially at smaller bones such as the metacarpals and phalanges. Additional characterization and superior delineation of cortices and fracture fragments was achieved by 2D MPRs. Histological correlation verified several of these imaging findings.ConclusionMicro-CT is able to screen Opt-mutant mice for osseous pathologies and furthermore characterize these anomalies. The modality seems superior to conventional radiography, but is not able to demonstrate cellular pathology. However, histology is destructive and more time- and material-consuming than micro-CT. Additional information may be gathered by 2D MPRs

Prevalence of abnormalities in knees detected by MRI in adults without knee osteoarthritis: population based observational study (Framingham Osteoarthritis Study)

Objective: To examine use of magnetic resonance imaging (MRI) of knees with no radiographic evidence of osteoarthritis to determine the prevalence of structural lesions associated with osteoarthritis and their relation to age, sex, and obesity. Design: Population based observational study. Setting: Community cohort in Framingham, MA, United States (Framingham osteoarthritis study). Participants: 710 people aged >50 who had no radiographic evidence of knee osteoarthritis (Kellgren-Lawrence grade 0) and who underwent MRI of the knee. Main outcome measures: Prevalence of MRI findings that are suggestive of knee osteoarthritis (osteophytes, cartilage damage, bone marrow lesions, subchondral cysts, meniscal lesions, synovitis, attrition, and ligamentous lesions) in all participants and after stratification by age, sex, body mass index (BMI), and the presence or absence of knee pain. Pain was assessed by three different questions and also by WOMAC questionnaire. Results: Of the 710 participants, 393 (55%) were women, 660 (93%) were white, and 206 (29%) had knee pain in the past month. The mean age was 62.3 years and mean BMI was 27.9. Prevalence of “any abnormality” was 89% (631/710) overall. Osteophytes were the most common abnormality among all participants (74%, 524/710), followed by cartilage damage (69%, 492/710) and bone marrow lesions (52%, 371/710). The higher the age, the higher the prevalence of all types of abnormalities detectable by MRI. There were no significant differences in the prevalence of any of the features between BMI groups. The prevalence of at least one type of pathology (“any abnormality”) was high in both painful (90-97%, depending on pain definition) and painless (86-88%) knees. Conclusions: MRI shows lesions in the tibiofemoral joint in most middle aged and elderly people in whom knee radiographs do not show any features of osteoarthritis, regardless of pain

Semiquantitative assessment of subchondral bone marrow edema-like lesions and subchondral cysts of the knee at 3T MRI: A comparison between intermediate-weighted fat-suppressed spin echo and Dual Echo Steady State sequences

Background\ud Choice of appropriate MR pulse sequence is important for any research studies using imaging-derived data. The aim of this study was to compare semiquantitative assessment of subchondral bone marrow edema-like lesions and subchondral cysts using intermediate-weighted (IW) fat-suppressed (fs) spin echo and Dual Echo Steady State (DESS) sequences on 3 T MRI.\ud \ud Methods\ud Included were 201 subjects aged 35-65 with frequent knee pain. 3T MRI was performed with the same sequence protocol as in the Osteoarthritis Initiative (OAI). In a primary reading subchondral bone marrow edema-like lesions were assessed according to the WORMS system. Two hundred subregions with such lesions were randomly chosen. The extent of subchondral bone marrow edema-like lesions was re-evaluated separately using sagittal IW fs and DESS sequences according to WORMS. Lesion size and confidence of the differentiation between subchondral bone marrow edema-like lesions and subchondral cysts located within or adjacent to them was rated from 0 to 3. Wilcoxon signed-rank tests and chi-square statistics were used to examine differences between the two sequences.\ud \ud Results\ud Of 200 subchondral bone marrow edema-like lesions detected by IW fs sequence, 93 lesions (46.5%) were not depicted by the DESS sequence. The IW fs sequence depicted subchondral bone marrow edema-like lesions to a larger extent than DESS (p < 0.0001), and the opposite was true for subchondral cysts. Confidence scores for differentiation of the two types of lesions were not significantly different between the two sequences.\ud \ud Conclusions\ud In direct comparison the IW fs sequence depicts more subchondral bone marrow edema-like lesions and better demonstrate the extent of their maximum size. The DESS sequence helps in the differentiation of subchondral bone marrow edema-like lesions and subchondral cysts. The IW fs sequence should be used for determination of lesion extent whenever the size of subchondral bone marrow edema-like lesions is the focus of attention

Reliability of semiquantitative assessment of osteophytes and subchondral cysts on tomosynthesis images by radiologists with different levels of expertise

PURPOSEWe aimed to assess reliability of the evaluation of osteophytes and subchondral cysts on tomosynthesis images when read by radiologists with different levels of expertise.MATERIALS AND METHODSForty subjects aged >40 years had both knees evaluated using tomosynthesis. Images were read by an “experienced” reader (musculoskeletal radiologist with prior experience) and an “inexperienced” reader (radiology resident with no prior experience). Readers graded osteophytes from 0 to 3 and noted the presence/absence of subchondral cysts in four locations of the tibiofemoral joint. Twenty knees were randomly selected and re-read. Inter- and intrareader reliabilities were calculated using overall exact percent agreement and weighted κ statistics. Diagnostic performance of the two readers was compared against magnetic resonance imaging readings by an expert reader (professor of musculoskeletal radiology).RESULTSThe experienced reader showed substantial intrareader reliability for graded reading of osteophytes (90%, κ=0.93), osteophyte detection (95%, κ=0.86) and cyst detection (95%, κ=0.83). The inexperienced reader showed perfect intrareader reliability for cyst detection (100%, κ=1.00) but intrareader reliability for graded reading (75%, κ=0.79) and detection (80%, κ=0.61) of osteophytes was lower than the experienced reader. Inter-reader reliability was 61% (κ=0.72) for graded osteophyte reading, 91% (κ=0.82) for osteophyte detection, and 88% (κ=0.66) for cyst detection. Diagnostic performance of the experienced reader was higher than the inexperienced reader regarding osteophyte detection (sensitivity range 0.74–0.95 vs. 0.54–0.75 for all locations) but diagnostic performance was similar for subchondral cysts.CONCLUSIONTomosynthesis offers excellent intrareader reliability regardless of the reader experience, but experience is important for detection of osteophytes

A prospective open label 2-8 year extension of the randomised controlled ICON trial on the long-term efficacy and safety of occipital nerve stimulation in medically intractable chronic cluster headache

BACKGROUND: We demonstrated in the randomised controlled ICON study that 48-week treatment of medically intractable chronic cluster headache (MICCH) with occipital nerve stimulation (ONS) is safe and effective. In L-ICON we prospectively evaluate its long-term effectiveness and safety. METHODS: ICON participants were enrolled in L-ICON immediately after completing ICON. Therefore, earlier ICON participants could be followed longer than later ones. L-ICON inclusion was stopped after the last ICON participant was enrolled in L-ICON and followed for ≥2 years by completing six-monthly questionnaires on attack frequency, side effects, subjective improvement and whether they would recommend ONS to others. Primary outcome was the change in mean weekly attack frequency 2 years after completion of the ICON study compared to baseline. Missing values for log-transformed attack-frequency were imputed for up to 5 years of follow-up. Descriptive analyses are presented as (pooled) geometric or arithmetic means and 95% confidence intervals. FINDINGS: Of 103 eligible participants, 88 (85%) gave informed consent and 73 (83%) were followed for ≥2 year, 61 (69%) ≥ 3 year, 33 (38%) ≥ 5 years and 3 (3%) ≥ 8.5 years. Mean (±SD) follow-up was 4.2 ± 2.2 years for a total of 370 person years (84% of potentially 442 years). The pooled geometric mean (95% CI) weekly attack frequency remained considerably lower after one (4.2; 2.8-6.3), two (5.1; 3.5-7.6) and five years (4.1; 3.0-5.5) compared to baseline (16.2; 14.4-18.3). Of the 49/88 (56%) ICON ≥50% responders, 35/49 (71%) retained this response and 15/39 (38%) ICON non-responders still became a ≥50% responder for at least half the follow-up period. Most participants (69/88; 78% [0.68-0.86]) reported a subjective improvement from baseline at last follow-up and 70/88 (81% [0.70-0.87]) would recommend ONS to others. Hardware-related surgery was required in 44/88 (50%) participants in 112/122 (92%) events (0.35 person-year-1 [0.28-0.41]). We didn't find predictive factors for effectiveness. INTERPRETATION: ONS is a safe, well-tolerated and long-term effective treatment for MICCH. FUNDING: The Netherlands Organisation for Scientific Research, the Dutch Ministry of Health, the NutsOhra Foundation from the Dutch Health Insurance Companies, and Medtronic.</p