T1Gd is reduced in bone marrow lesions overlying cartilage in the hip.

OBJECTIVE: Bone Marrow Lesions (BMLs) are areas in bone with high fluid signal on MRI associated with painful and progressive OA. While cartilage near BMLs in the knee has been shown to be degenerated, this relationship has not been investigated in the hip. RESEARCH QUESTION: is T1Gd lower in areas of cartilage overlying BMLs in the hip? DESIGN: 128 participants were recruited from a population-based study of hip pain in 20-49-year-olds. Proton-density weighted fat-suppressed and delayed Gadolinium Enhanced MR Imaging of Cartilage (dGEMRIC) images were acquired to locate BMLs and quantify hip cartilage health. BML and cartilage images were registered and cartilage was separated into BML overlying and surrounding regions. Mean T1Gd was measured in 32 participants with BMLs in both cartilage regions and in matched regions in 32 age- and sex-matched controls. Mean T1Gd in the overlying cartilage was compared using linear mixed-effects models between BML and control groups for acetabular and femoral BMLs, and between cystic and non-cystic BML groups. RESULTS: Mean T1Gd of overlying cartilage was lower in the BML group compared to the control group (acetabular: -105 ms; 95% CI: -175, -35; femoral: -8 ms; 95% CI: -141, 124). Mean T1Gd in overlying cartilage was lower in cystic compared to non-cystic BML subjects, but the confidence interval is too large to provide certainty in this difference (-3 [95% CI: -126, 121]). CONCLUSIONS: T1Gd is reduced in overlying cartilage in hips from a population-based sample of adults aged 20-49, which suggests BMLs are associated with local cartilage degeneration in hips.

The relation between the biochemical composition of knee articular cartilage and quantitative MRI: a systematic review and meta-analysis.

OBJECTIVE: Early and non-invasive detection of osteoarthritis (OA) is required to enable early treatment and monitoring of interventions. Some of the earliest signs of OA are the change in proteoglycan and collagen composition. The aim of this study is to establish the relations between quantitative magnetic resonance imaging (MRI) and biochemical concentration and organization in knee articular cartilage. METHODS: A preregistered systematic literature review was performed using the databases PubMed and Embase. Papers were included if quantitative MRI and a biochemical assay or polarized light microscopy (PLM) was performed on knee articular cartilage, and a quantified correlation was described. The extracted correlations were pooled using a random effects model. RESULTS: 21 papers were identified. The strongest pooled correlation was found for delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) vs proteoglycan concentration (r = 0.59). T1ρ relaxation times are inversely correlated to proteoglycan concentration (r = -0.54). A weak correlation between T2 relaxation times and proteoglycans was found (r = -0.38). No correlation between T2 relaxation time and collagen concentration was found (r = -0.02). A heterogeneous set of correlations between T2 relaxation times and PLM were identified, including strong correlations to anisotropy. CONCLUSION: DGEMRIC measures are significantly correlated to proteoglycan concentration. The needed contrast agent is however a disadvantage; the T1ρ sequence was found as a non-invasive alternative. Remarkably, no correlation was found between T2 relaxation times and collagen concentration. T2 relaxation times is related to organization, rather than concentration of collagen fibers. PROSPERO ID: CRD42020168337.

Multi-centre randomised controlled trial comparing arthroscopic hip surgery to physiotherapist-led care for femoroacetabular impingement (FAI) syndrome on hip cartilage metabolism: the Australian FASHIoN trial.

BACKGROUND: Arthroscopic surgery for femoroacetabular impingement syndrome (FAI) is known to lead to self-reported symptom improvement. In the context of surgical interventions with known contextual effects and no true sham comparator trials, it is important to ascertain outcomes that are less susceptible to placebo effects. The primary aim of this trial was to determine if study participants with FAI who have hip arthroscopy demonstrate greater improvements in delayed gadolinium-enhanced magnetic resonance imaging (MRI) of cartilage (dGEMRIC) index between baseline and 12 months, compared to participants who undergo physiotherapist-led management. METHODS: Multi-centre, pragmatic, two-arm superiority randomised controlled trial comparing physiotherapist-led management to hip arthroscopy for FAI. FAI participants were recruited from participating orthopaedic surgeons clinics, and randomly allocated to receive either physiotherapist-led conservative care or surgery. The surgical intervention was arthroscopic FAI surgery. The physiotherapist-led conservative management was an individualised physiotherapy program, named Personalised Hip Therapy (PHT). The primary outcome measure was change in dGEMRIC score between baseline and 12 months. Secondary outcomes included a range of patient-reported outcomes and structural measures relevant to FAI pathoanatomy and hip osteoarthritis development. Interventions were compared by intention-to-treat analysis. RESULTS: Ninety-nine participants were recruited, of mean age 33 years and 58% male. Primary outcome data were available for 53 participants (27 in surgical group, 26 in PHT). The adjusted group difference in change at 12 months in dGEMRIC was -59 ms (95%CI - 137.9 to - 19.6) (p = 0.14) favouring PHT. Hip-related quality of life (iHOT-33) showed improvements in both groups with the adjusted between-group difference at 12 months showing a statistically and clinically important improvement in arthroscopy of 14 units (95% CI 5.6 to 23.9) (p = 0.003). CONCLUSION: The primary outcome of dGEMRIC showed no statistically significant difference between PHT and arthroscopic hip surgery at 12 months of follow-up. Patients treated with surgery reported greater benefits in symptoms at 12 months compared to PHT, but these benefits are not explained by better hip cartilage metabolism. TRIAL REGISTRATION DETAILS: Australia New Zealand Clinical Trials Registry reference: ACTRN12615001177549 . Trial registered 2/11/2015.

Feasibility of using half-dose Gd-BOPTA for delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) at the knee, compared with standard-dose Gd-DTPA.

BACKGROUND: We sought to replace full-dose Gd-DTPA with safer and lower-dose contrast agents for delayed gadolinium-enhanced MRI of cartilage (dGEMRIC). Gd-BOPTA has a lower intrinsic nephrogenic systemic fibrosis risk and a 2-fold higher relaxivity at 3T; thus, the contrast agent dose may be halved, further reducing contrast agent-dependent risks. PURPOSE: To compare the feasibility of using half-dose, high-relaxivity Gd-BOPTA vs. standard-dose Gd-DTPA for dGEMRIC. STUDY TYPE: Prospective observational study. SUBJECTS: Eleven healthy volunteers (five women, mean age 25.7 years) and 10 patients with knee pain (three women, mean age 36.7 years; nine with chondromalacia). FIELD STRENGTH/SEQUENCES: 3D T1 -weighted volumetric breath-hold examination (VIBE) sequence at 3T. ASSESSMENT: Knee dGEMRIC was performed twice, first using 0.1 mmol/kg Gd-BOPTA and 4 weeks later using 0.2 mmol/kg Gd-DTPA. Contrast penetration was studied using pre- and 60-120-min postcontrast imaging in volunteers and pre- and 90-min postcontrast imaging in patients. Femoral cartilage lesions were assessed using modified whole-organ MRI scores. Healthy cartilage and partial-thickness lesions were compared using region-of-interest analyses by independent readers. STATISTICAL TESTS: Linear mixed-effect-models, area under receiver-operating-characteristic curve (AUC) analysis, intraclass correlation (ICC). RESULTS: In healthy volunteers, Gd-BOPTA and Gd-DTPA T1 -values did not differ significantly at any timepoint (P = 0.164-0.995). In patients, Gd-BOPTA T1 -values (743.33 ± 72.015 msec) were higher than Gd-DTPA T1 -values (681.24 ± 67.635 msec, P = 0.030). Gd-BOPTA and Gd-DTPA detected chondromalacia areas equally well, with significantly lower T1 -values than in healthy cartilage (P < 0.001) and nonsignificantly different AUCs (0.92 and 0.96, P = 0.27). The absolute decrease in T1 -values between healthy and pathological cartilage was similar (Gd-BOPTA: 149.59 msec; Gd-DTPA: 149.44 msec, P = 0.99). ICCs were 0.83-0.98 for Gd-BOPTA and 0.80-0.98 for Gd-DTPA. DATA CONCLUSION: Gd-BOPTA might be used at half the Gd-DTPA dose in dGEMRIC, with similar contrast penetration and T1 -values in healthy cartilage and noninferior detection of cartilage damage. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 5 J. Magn. Reson. Imaging 2020;51:144-154.

Higher aggrecan 1-F21 epitope concentration in synovial fluid early after anterior cruciate ligament injury is associated with worse knee cartilage quality assessed by gadolinium enhanced magnetic resonance imaging 20 years later.

BACKGROUND: To investigate if cartilage related biomarkers in synovial fluid are associated with knee cartilage status 20 years after an anterior cruciate ligament (ACL) injury. METHODS: We studied 25 patients with a complete ACL rupture without subsequent ACL reconstruction or radiographic knee OA. All had a delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC) 20 years after the ACL injury, using the T1 transverse relaxation time in the presence of gadolinium (T1Gd) which estimates the concentration of glycosaminoglycans in hyaline cartilage. Synovial fluid samples were aspirated acutely (between 0 and 18 days) and during 1 to 5 follow up visits between 0.5 and 7.5 years after injury. We quantified synovial fluid concentrations of aggrecan (epitopes 1-F21 and ARGS), cartilage oligomeric matrix protein, matrix metalloproteinase-3 and tissue inhibitor of metalloproteinase-1 by immunoassays, and sulfated glycosaminoglycans by Alcian blue precipitation. Western blot was used for qualitative analyses of aggrecan fragments in synovial fluid and cartilage samples. RESULTS: Western blot indicated that the 1-F21 epitope was located within the chondroitin sulfate 2 region of aggrecan. Linear regression analyses (adjusted for age, sex, body mass index and time between injury and sampling) showed that acute higher synovial fluid 1-F21-aggrecan concentrations were associated with shorter T1Gd values 20 years after injury, i.e. inferior cartilage quality (standardized effects between - 0.67 and - 1.0). No other statistically significant association was found between molecular biomarkers and T1Gd values. CONCLUSION: Higher acute synovial fluid 1-F21-aggrecan concentrations in ACL injured patients, who managed to cope without ACL reconstruction and were without radiographic knee OA, were associated with inferior knee cartilage quality assessed by dGEMRIC 20 years after injury.

Osteoarthritis development related to cartilage quality-the prognostic value of dGEMRIC after anterior cruciate ligament injury.

OBJECTIVE: Rupture of the anterior cruciate ligament (ACL) increases the risk of developing osteoarthritis (OA). Delayed Gadolinium enhanced magnetic resonance imaging (MRI) of cartilage (dGEMRIC) investigates cartilage integrity through T1-analysis after intravenous contrast injection. A high dGEMRIC index represents good cartilage quality. The main purpose of this prospective cohort study was to investigate the prognostic value of the dGEMRIC index regarding future knee OA. METHOD: 31 patients with ACL injury (mean age 27 ± 6.7 (±SD) years, 19 males) were examined after 2 years with 1.5T dGEMRIC of femoral cartilage. Re-examination 14 years post-injury included weight-bearing knee radiographs, Lysholm and Knee Osteoarthritis Outcome Score (KOOS). RESULTS: At the 14-year follow up radiographic OA (ROA) was present in 68% and OA symptoms (SOA) in 42% of the injured knees. The dGEMRIC index of the medial compartment was lower in knees that developed medial ROA, 325 ± 68 (ms±SD) vs 376 ± 47 (51 (7-94)) (difference of means (95% confidence interval (CI))), in patients that developed symptomatic OA (SOA), 327 ± 61 vs 399 ± 42 (52 (11-93)), and poor knee function 337 ± 54 vs 381 ± 52 (48 (7-89)) compared to those that did not develop ROA, SOA or poor function. The dGEMRIC index correlated negatively with the OARSI osteophyte score in medial (r = -0.44, P = 0.01) and lateral (r = -0.38, P = 0.03) compartments. CONCLUSION: The associations between a low dGEMRIC index and future ROA, as well as SOA, are in agreement with previous studies and indicate that dGEMRIC has a prognostic value for future knee OA.

Pre-contrast T1 and cartilage thickness as confounding factors in dGEMRIC when evaluating human cartilage adaptation to physical activity.

BACKGROUND: The dGEMRIC (delayed Gadolinium-Enhanced MRI of Cartilage) technique has been used in numerous studies for quantitative in vivo evaluation of the relative glycosaminoglycan (GAG) content in cartilage. The purpose of this study was to determine the influence of pre-contrast T1 and cartilage thickness when assessing knee joint cartilage quality with dGEMRIC. METHODS: Cartilage thickness and T1 relaxation time were measured in the central part of the femoral condyles before and two hours after intravenous Gd-DTPA2- administration in 17 healthy volunteers from a previous study divided into two groups: 9 sedentary volunteers and 8 exercising elite runners. Results were analyzed in superficial and a deep weight-bearing, as well as in non-weight-bearing regions of interest. RESULTS: In the medial compartment, the cartilage was thicker in the exercising group, in weight-bearing and non-weight-bearing segments. In most of the segments, the T1 pre-contrast value was longer in the exercising group compared to the sedentary group. Both groups had a longer pre-contrast T1 in the superficial cartilage than in the deep cartilage. In the superficial cartilage, the gadolinium concentration was independent of cartilage thickness. In contrast, there was a linear correlation between the gadolinium concentration and cartilage thickness in the deep cartilage region. CONCLUSION: Cartilage pre-contrast T1 and thickness are sources of error in dGEMRIC that should be considered when analysing bulk values. Our results indicate that differences in cartilage structure due to exercise and weight-bearing may be less pronounced than previously demonstrated.

Single- vs. double-dose gadolinium contrast in delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) in knee osteoarthritis: is dose reduction possible on 3-T MRI?

BACKGROUND: Reduction in gadolinium (Gd) contrast agents is wanted due to the uncertainty of the potential side effects. PURPOSE: To investigate whether it is possible to reduce the contrast dose from conventional double dose to single dose when increasing the field strength from 1.5-T to 3-T for separating early cartilage degeneration from healthy cartilage, assessed by delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC). MATERIAL AND METHODS: Nine patients with knee osteoarthritis (OA), Kellgren-Lawrence grade (KLG) 1-4, were recruited from an ongoing weight loss cohort study. dGEMRIC was performed at 3-T using single (0.1 mmoI/kg) and double (0.2 mmoI/kg) doses of intravenous (i.v.) Gd-DTPA2-. Regions of interest (ROls) were drawn around the posterior weight-bearing femoral knee cartilage in lateral and medial compartments. In five medial compartments ROIs could not be drawn due to severe degeneration of cartilage. T1-relaxation times were compared to previously published values from 1.5-T and to non-contrast values from 3-T. RESULTS: Mean dGEMRIC T1-relaxation time in the lateral compartment was 769 ms for single dose vs. 561 ms for double dose ( P < 0.0001); and 685 ms for single dose vs. 454 ms for double dose ( P = 0.004) in the medial compartment. CONCLUSION: We found a dose-response relationship between single and double doses of Gd-DTPA2- using 3-T in knee OA patients, similar to the findings at 1.5-T. Compared to the T1-relaxation time at 3-T without contrast (1240 ms), this further separation between OA and normal cartilage indicates that "single dose" dGEMRIC could be sufficient for cartilage health assessment at 3-T.

Point of no return for improvement of cartilage quality indicated by dGEMRIC before and after weight loss in patients with knee osteoarthritis: a cohort study.

Background It has been demonstrated that weight loss improves symptoms in obese subjects with knee osteoarthritis (KOA). A parallel change in cartilage morphology remains to be demonstrated. Purpose To demonstrate a parallel change in cartilage morphology. Material and Methods Obese patients with KOA were examined before and after weight loss over 16 weeks. Target knee joints were radiographically assessed by the Kellgren/Lawrence grading (KLG) system. Patients with KLG-1 and 2 changes in the lateral compartment were included. Delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) was performed using intra-articular contrast. Results Nine patients with lateral KLG-1 and ten patients with lateral KLG-2 were studied. There were no group differences regarding the lateral compartment baseline dGEMRIC T1 values: median = 497 ms (KLG-1) and 533 ms (KLG-2) ( P = 0.12), or regarding reduction in body mass index (BMI) after 16 weeks: 12.8% versus 11.4% ( P = 0.74). In the KLG-1 group, several cases of increased dGEMRIC T1 values were seen and median value decreased significantly less than in KLG-2 group (15 ms versus 41 ms, P = 0.03) after weight loss. Conclusion Improvement of cartilage quality, assessed with dGEMRIC, after weight loss might be possible in early stage KOA (KLG-1), but not in later stage KOA (KLG-2). The results may suggest a point of no return for improvement of cartilage quality that should be tested in larger trials.

Knee dGEMRIC at 7 T: comparison against 1.5 T and evaluation of T1-mapping methods.

BACKGROUND: dGEMRIC (delayed Gadolinium Enhanced Magnetic Resonance Image of Cartilage) is a well-established technique for cartilage quality assessment in osteoarthritis at clinical field strengths. The method is robust, but requires injection of contrast agent and a cumbersome examination procedure. New non-contrast-agent-based techniques for cartilage quality assessment are currently being developed at 7 T. However, dGEMRIC remains an important reference technique during this development. The aim of this work was to compare T1 mapping for dGEMRIC at 7 T and 1.5 T, and to evaluate three T1-mapping methods at 7 T. METHODS: The knee of 10 healthy volunteers and 9 patients with early signs of cartilage degradation were examined at 1.5 T and 7 T after a single (one) contrast agent injection (Gd-(DTPA)2-). Inversion recovery (IR) sequences were acquired at both field strengths, and at 7 T variable flip angle (VFA) and Look-Locker (LL) sequences were additionally acquired. T1 maps were calculated and average T1 values were estimated within superficial and deep regions-of-interest (ROIs) in the lateral and medial condyles, respectively. RESULTS: T1 values were 1.8 (1.4-2.3) times longer at 7 T. A strong correlation was detected between 1.5 T and 7 T T1 values (r = 0.80). For IR, an additional inversion time was required to avoid underestimation (bias±limits of agreement - 127 ± 234 ms) due to the longer T1 values at 7 T. Out of the two 3D sequences tested, LL resulted in more accurate and precise T1 estimation compared to VFA (average bias±limits of agreement LL: 12 ± 202 ms compared to VFA: 25 ± 622 ms). For both, B1 correction improved agreement to IR. CONCLUSION: With an adapted sampling scheme, dGEMRIC T1 mapping is feasible at 7 T and correlates well to 1.5 T. If 3D is to be used for T1 mapping of the knee at 7 T, LL is preferred and VFA is not recommended. For VFA and LL, B1 correction is necessary for accurate T1 estimation.

Diagnostic and prognostic value of delayed Gadolinium Enhanced Magnetic Resonance Imaging of Cartilage (dGEMRIC) in early osteoarthritis of the hip.

BACKGROUND: Delayed Gadolinium Enhanced Magnetic Resonance Imaging of Cartilage (dGEMRIC) can detect glycosaminoglycan loss in the acetabular cartilage of asymptomatic individuals with cam morphology. The aims of this study were to explore the relationship between cam morphology and dGEMRIC values, and to explore whether baseline dGEMRIC can predict the development of radiographic hip osteoarthritis. METHODS: Prospective cohort (SibKids) study with clinical, radiographic, and MRI assessment at baseline and five-year follow-up (n = 34). The dGEMRIC values of cartilage regions were correlated with measures of cam morphology. Receiver operating characteristic (ROC) analysis was applied to baseline variables to predict radiographic loss of joint space width. RESULTS: Superolateral acetabular cartilage dGEMRIC values were significantly lower in participants with cam morphology (P < 0.001), defined as an alpha angle greater than 60°. There was a negative correlation between alpha angle and the dGEMRIC value of adjacent acetabular cartilage. This relationship was strongest superoanteriorly (r = -0.697 P < 0.001). There was a positive correlation between baseline dGEMRIC and the magnitude of joint space width narrowing (r = 0.398 P = 0.030). ROC analysis of combined baseline variables (positive impingement test, alpha angle, dGEMRIC ratio) gave an Area Under the Curve (AUC) of 0.75 for predicting joint space width narrowing greater than 0.5 mm within 5 years. CONCLUSIONS: The size and position of cam morphology determines the severity and location of progressive cartilage damage, supporting the biomechanical aetiology of femoroacetabular impingement. Baseline dGEMRIC is able to predict the development of radiographic osteoarthritis. Compositional MRI offers the potential to identify patients who may benefit from early intervention to prevent the development of osteoarthritis.

Influence of delayed gadolinium enhanced MRI of cartilage (dGEMRIC) protocol on T2-mapping: is it possible to comprehensively assess knee cartilage composition in one post-contrast MR examination at 3 Tesla?

OBJECTIVE: To evaluate the possibility of assessing knee cartilage with T2-mapping and delayed gadolinium enhanced magnetic resonance imaging (MRI) of cartilage (dGEMRIC) in one post-contrast MR examination at 3 Tesla (T). DESIGN: T2 mapping was performed in 10 healthy volunteers at baseline; directly after baseline; after 10 min of cycling; and after 90 min delay, and in 16 osteoarthritis patients before and after intravenous administration of a double dose gadolinium dimeglumine contrast agent, reflecting key dGEMRIC protocol elements. Differences in T2 relaxation times between each timepoint and baseline were calculated for 6 cartilage regions using paired t tests or Wilcoxon signed-rank tests and the smallest detectable change (SDC). RESULTS: After cycling, a significant change in T2 relaxation times was found in the lateral weight-bearing tibial plateau (+1.0 ms, P = 0.04). After 90 min delay, significant changes were found in the lateral weight-bearing femoral condyle (+1.2 ms, P = 0.03) and the lateral weight-bearing tibial plateau (+1.3 ms, P = 0.01). In these regions of interests (ROIs), absolute differences were small and lower than the corresponding SDCs. T2-mapping after contrast administration only showed statistically significantly lower T2 relaxation times in the medial posterior femoral condyle (-2.4 ms, P < 0.001) with a change exceeding the SDC. CONCLUSION: Because dGEMRIC protocol elements resulted in only small differences in T2 relaxation times that were not consistent and lower than the SDC in the majority of regions, our results suggest that T2-mapping and dGEMRIC can be performed reliably in a single imaging session to assess cartilage biochemical composition in knee osteoarthritis (OA) at 3 T.

Feasibility of gadoteric acid for delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) at the wrist and knee and comparison with Gd-DTPA.

PURPOSE: To assess the feasibility of gadoteric acid for delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC) and to compare the dGEMRIC values obtained using gadoteric acid with those obtained by an equimolar dose of Gd-DTPA. MATERIALS AND METHODS: At 3T, dGEMRIC of the wrist was performed twice using a T1 -weighted 3D-volumetric interpolated breath-hold examination sequence in 16 healthy volunteers (10 women; mean age 26.0 years) using gadoteric acid first and Gd-DTPA 3 weeks later. In addition, 24 patients with knee pain were examined using gadoteric acid (n = 12; seven women; mean age 45.8 years) or Gd-DTPA (n = 12; four women; mean age 47.1 years). T1 values, the relative decrease in T1 , and the delta R1 were compared using t-tests. Interobserver agreement was assessed using the intraclass correlation (ICC) between two independent readers. RESULTS: At the wrist, there was no significant difference in delta R1 values (0.34 ± 0.10/s, 95% confidence interval [0.30;0.38]/s for gadoteric acid and 0.32 ± 0.09 [0.29;0.35]/s for Gd-DTPA, P = 0.24) or the relative decrease in T1 (0.25 ± 0.06 [0.29;0.35] msec for gadoteric acid and 0.24 ± 0.05 [0.22;0.27] msec for Gd-DTPA, P = 0.35). High observer agreement was found at precontrast (ICC = 0.87, P < 0.001) and postcontrast (ICC = 0.89, P < 0.001). Similarly, at the knee, there was no significant difference in delta R1 (0.39 ± 0.18 [0.32;0.47]/s for gadoteric acid and 0.41 ± 0.09 [0.38;0.45]/s for Gd-DTPA, P = 0.59) or the relative decrease in T1 (0.30 ± 0.10 [0.26;0.34] msec for gadoteric acid and 0.33 ± 0.05 [0.30;0.35] msec for Gd-DTPA, P = 0.28). High ICCs of 0.96 (P < 0.01) were noted both at precontrast and postcontrast. CONCLUSION: dGEMRIC using gadoteric acid is feasible and yields comparable values when compared with Gd-DTPA. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2017;46:1433-1440.

Delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) and T2 mapping at 3T MRI of the wrist: Feasibility and clinical application.

PURPOSE: To assess the feasibility of delayed gadolinium-enhanced magnetic resonance imaging (MRI) of cartilage (dGEMRIC) and T2 mapping for biochemical imaging of the wrist at 3T. MATERIALS AND METHODS: Seventeen patients with wrist pain (mean age, 41.4 ± 13.1 years) including a subgroup with chondromalacia (n = 11) and 15 healthy volunteers (26.0 ± 2.2 years) underwent dGEMRIC and T2 mapping at 3T. For dGEMRIC, the optimum time window after contrast-injection (gadopentetate dimeglumine) was defined as the plateau of the T1 curve of repeated measurements 15-90 minutes postinjection and assessed in all volunteers. Reference values of healthy-appearing cartilage from all individuals and values in areas of chondromalacia were assessed using region-of-interest analyses. Receiver-operating-characteristic analyses were applied to assess discriminatory ability between damaged and normal cartilage. RESULTS: The optimum time window was 45-90 minutes, and the 60-minute timepoint was subsequently used. In chondromalacia, dGEMRIC values were lower (551 ± 84 msec, P < 0.001), and T2 values higher (63.9 ± 17.7, P = 0.001) compared to healthy-appearing cartilage of the same patient. Areas under the curve did not significantly differ between dGEMRIC (0.91) and T2 mapping (0.99; P = 0.17). In healthy-appearing cartilage of volunteers and patients, mean dGEMRIC values were 731.3 ± 47.1 msec and 674.6 ± 72.1 msec (P = 0.01), and mean T2 values were 36.5 ± 5 msec and 41.1 ± 3.2 msec (P = 0.009), respectively. CONCLUSION: At 3T, dGEMRIC and T2 mapping are feasible for biochemical cartilage imaging of the wrist. Both techniques allow separation and biochemical assessment of thin opposing cartilage surfaces and can distinguish between healthy and damaged cartilage. LEVEL OF EVIDENCE: 3 J. Magn. Reson. Imaging 2017;45:381-389.

Delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) and T2 mapping of talar osteochondral lesions: Indicators of clinical outcomes.

PURPOSE: To evaluate the utility of delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC) and T2 mapping in evaluation of type II osteochondral lesions (OCLs) of the talus and define cutoff values for identifying patients with good/poor clinical outcomes. MATERIALS AND METHODS: 28 patients (mean age, 42.3 years) underwent T2 mapping and dGEMRIC at least 1.5 years (mean duration, 3.5 years) after microfracture (n = 12) or conservative (n = 16) treatment for type II OCL. Clinical outcomes were considered good with an American Orthopedic Foot and Ankle Society score ≥80. The T1 /T2 -values and indices of repair tissue (RT; cartilage above the OCL) were compared to those of the adjacent normal cartilage (NC) by region-of-interest analysis. The ability of the two methods to discriminate RT from NC was determined by area under the receiver operating characteristics curve (AUC) analysis. The Youden index was maximized for T1 /T2 measures for identifying cutoff values indicative of good/poor clinical outcomes. RESULTS: Repair tissue exhibited lower dGEMRIC values (629.83 vs. 738.51 msec) and higher T2 values (62.07 vs. 40.69 msec) than NC (P < 0.001). T2 mapping exhibited greater AUC than dGEMRIC (0.88 vs. 0.69; P = 0.0398). All T1 measures exhibited higher maximized Youden indices than the corresponding T2 measures. The highest maximized Youden index for T1difference was observed at a cutoff value of 84 msec (sensitivity, 78%; specificity, 83%). CONCLUSION: While T2 mapping is superior to dGEMRIC in discriminating RT, the latter better identifies good/poor clinical outcomes in patients with type II talar OCL. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2017;46:1601-1610.

Prestructural cartilage assessment using MRI.

Cartilage loss is irreversible, and to date, no effective pharmacotherapies are available to protect or regenerate cartilage. Quantitative prestructural/compositional MR imaging techniques have been developed to characterize the cartilage matrix quality at a stage where abnormal findings are early and potentially reversible, allowing intervention to halt disease progression. The goal of this article is to critically review currently available technologies, present the basic concept behind these techniques, but also to investigate their suitability as imaging biomarkers including their validity, reproducibility, risk prediction and monitoring of therapy. Moreover, we highlighted important clinical applications. This review article focuses on the currently most relevant and clinically applicable technologies, such as T2 mapping, T2*, T1ρ, delayed gadolinium enhanced MRI of cartilage (dGEMRIC), sodium imaging and glycosaminoglycan chemical exchange saturation transfer (gagCEST). To date, most information is available for T2 and T1ρ mapping. dGEMRIC has also been used in multiple clinical studies, although it requires Gd contrast administration. Sodium imaging and gagCEST are promising technologies but are dependent on high field strength and sophisticated software and hardware. LEVEL OF EVIDENCE: 5 J. Magn. Reson. Imaging 2017;45:949-965.

Protocol for a multi-centre randomised controlled trial comparing arthroscopic hip surgery to physiotherapy-led care for femoroacetabular impingement (FAI): the Australian FASHIoN trial.

BACKGROUND: Femoroacetabular impingement syndrome (FAI), a hip disorder affecting active young adults, is believed to be a leading cause of hip osteoarthritis (OA). Current management approaches for FAI include arthroscopic hip surgery and physiotherapy-led non-surgical care; however, there is a paucity of clinical trial evidence comparing these approaches. In particular, it is unknown whether these management approaches modify the future risk of developing hip OA. The primary objective of this randomised controlled trial is to determine if participants with FAI who undergo hip arthroscopy have greater improvements in hip cartilage health, as demonstrated by changes in delayed gadolinium-enhanced magnetic resonance imaging (MRI) of cartilage (dGEMRIC) index between baseline and 12 months, compared to those who undergo physiotherapy-led non-surgical management. METHODS: This is a pragmatic, multi-centre, two-arm superiority randomised controlled trial comparing hip arthroscopy to physiotherapy-led management for FAI. A total of 140 participants with FAI will be recruited from the clinics of participating orthopaedic surgeons, and randomly allocated to receive either surgery or physiotherapy-led non-surgical care. The surgical intervention involves arthroscopic FAI surgery from one of eight orthopaedic surgeons specialising in this field, located in three different Australian cities. The physiotherapy-led non-surgical management is an individualised physiotherapy program, named Personalised Hip Therapy (PHT), developed by a panel to represent the best non-operative care for FAI. It entails at least six individual physiotherapy sessions over 12 weeks, and up to ten sessions over six months, provided by experienced musculoskeletal physiotherapists trained to deliver the PHT program. The primary outcome measure is the change in dGEMRIC score of a ROI containing both acetabular and femoral head cartilages at the chondrolabral transitional zone of the mid-sagittal plane between baseline and 12 months. Secondary outcomes include patient-reported outcomes and several structural and biomechanical measures relevant to the pathogenesis of FAI and development of hip OA. Interventions will be compared by intention-to-treat analysis. DISCUSSION: The findings will help determine whether hip arthroscopy or an individualised physiotherapy program is superior for the management of FAI, including for the prevention of hip OA. TRIAL REGISTRATION: Australia New Zealand Clinical Trials Registry reference: ACTRN12615001177549 . Trial registered 2/11/2015 (retrospectively registered).

Residual hip dysplasia at 1 year after treatment for neonatal hip instability is not related to degenerative joint disease in young adulthood: a 21-year follow-up study including dGEMRIC.

OBJECTIVE: Developmental dysplasia of the hip (DDH) is associated with an increased risk of early hip osteoarthritis (OA). We aimed to examine the outcome at the completion of growth in a cohort of children who had residual acetabular dysplasia at age 1 year following early treatment for neonatal instability of the hip (NIH). DESIGN: We examined 21 of 30 subjects who had been treated with the von Rosen splint neonatally for NIH and had residual acetabular dysplasia at age 1 year. Mean follow-up time was 21 years (range 17-24). Signs of OA and acetabular dysplasia were assessed by radiography. Cartilage quality was assessed by delayed Gadolinium Enhanced Magnetic Resonance Imaging of Cartilage (dGEMRIC), a tool for molecular imaging of cartilage quality, at 1.5 T. Patient reported outcome (PRO) was assessed by the 12-item WOMAC score. RESULTS: No study participant had radiographic OA (defined as Kellgren-Lawrence grade ≥2) or minimum joint space width (JSW) ≤2 mm. The mean dGEMRIC index was 630 ms (95% CI: 600-666, range: 516-825) suggesting good cartilage quality. The mean 12-item WOMAC score was 1.2. Two of three radiographic measurements of DDH correlated positively to the dGEMRIC index. CONCLUSIONS: Children treated neonatally for NIH have good hip function and no signs of cartilage degeneration at 21-year follow-up, despite residual dysplasia at age 1 year. Unexpectedly, radiographic signs of dysplasia were associated with better cartilage quality, as assessed with dGEMRIC. This may indicate cartilage adaptation to increased mechanical stress in mild hip dysplasia.

Morphological imaging and T2 and T2* mapping of hip cartilage at 7 Tesla MRI under the influence of intravenous gadolinium.

OBJECTIVES: To investigate the influence of intravenous gadolinium on cartilage T2 and T2* relaxation times and on morphological image quality at 7-T hip MRI. METHODS: Hips of 11 healthy volunteers were examined at 7 T. Multi-echo sequences for T2 and T2* mapping, 3D T1 volumetric interpolated breath-hold examination (VIBE) and double-echo steady-state (DESS) sequences were acquired before and after intravenous application of gadolinium according to a delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) protocol. Cartilage relaxation times were measured in both scans. Morphological sequences were assessed quantitatively using contrast ratios and qualitatively using a 4-point Likert scale. Student's t-test, Pearson's correlation (ρ) and Wilcoxon sign-rank test were used for statistical comparisons. RESULTS: Pre- and post-contrast T2 and T2* values were highly correlated (T2: acetabular: ρ = 0.76, femoral: ρ = 0.77; T2*: acetabular: ρ = 0.80, femoral: ρ = 0.72). Gadolinium enhanced contrasts between cartilage and joint fluid in DESS and T1 VIBE according to the qualitative (p = 0.01) and quantitative (p < 0.001) analysis. The delineation of acetabular and femoral cartilage and the labrum predominantly improved with gadolinium. CONCLUSIONS: Gadolinium showed no relevant influence on T2 or T2* relaxation times and improved morphological image quality at 7 T. Therefore, morphological and quantitative sequences including dGEMRIC can be conducted in a one-stop-shop examination. KEY POINTS: • Hip cartilage T2 values correlate highly before and after gadolinium at 7 T • Hip cartilage T2* values correlate highly before and after enhancement at 7 T • Morphological hip cartilage imaging benefits from intravenous gadolinium at 7 T • The delineation of acetabular and femoral cartilage can be improved by gadolinium • Morphological and quantitative sequences including dGEMRIC can be combined as a one-stop-shop examination.

7 Tesla quantitative hip MRI: T1, T2 and T2* mapping of hip cartilage in healthy volunteers.

OBJECTIVES: To evaluate the technical feasibility and applicability of quantitative MR techniques (delayed gadolinium-enhanced MRI of cartilage (dGEMRIC), T2 mapping, T2* mapping) at 7 T MRI for assessing hip cartilage. METHODS: Hips of 11 healthy volunteers were examined at 7 T MRI with an 8-channel radiofrequency transmit/receive body coil using multi-echo sequences for T2 and T2* mapping and a dual flip angle gradient-echo sequence before (T10) and after intravenous contrast agent administration (T1Gd; 0.2 mmol/kg Gd-DTPA(2-) followed by 0.5 h of walking and 0.5 h of rest) for dGEMRIC. Relaxation times of cartilage were measured manually in 10 regions of interest. Pearson's correlations between R1delta = 1/T1Gd - 1/T10 and T1Gd and between T2 and T2* were calculated. Image quality and the delineation of acetabular and femoral cartilage in the relaxation time maps were evaluated using discrete rating scales. RESULTS: High correlations were found between R1delta and T1Gd and between T2 and T2* relaxation times (all p < 0.01). All techniques delivered diagnostic image quality, with best delineation of femoral and acetabular cartilage in the T2* maps (mean 3.2 out of a maximum of 4 points). CONCLUSIONS: T1, T2 and T2* mapping of hip cartilage with diagnostic image quality is feasible at 7 T. To perform dGEMRIC at 7 T, pre-contrast T1 mapping can be omitted. KEY POINTS: • dGEMRIC of hip cartilage with diagnostic image quality is feasible at 7 T. • To perform dGEMRIC at 7 T, pre-contrast T1 mapping can be omitted. • T2(*) mapping of hip cartilage with diagnostic image quality is feasible at 7 T. • T2 and T2* relaxation times of cartilage were highly correlated at 7 T. • Best delineation of femoral and acetabular cartilage was found in T2* maps.