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[18F]Sodium fluoride PET-MRI detects increased metabolic bone response to whole-joint loading stress in osteoarthritic knees

Watkins, L E; Haddock, B; MacKay, J W; Baker, J; Uhlrich, S D; Mazzoli, V; Gold, G E; Kogan, F
OBJECTIVE:F]NaF PET-MRI was used to study the acute joint response to exercise in OA knees, and compare relationships between regions of increased uptake after loading and structural OA progression two years later. METHODS:> 3) were identified and the presence of structural MRI features was noted. Five participants returned two years later to assess structural change on MRI. RESULTS:P < 0.001) that differed by bone region. CONCLUSION:There were regional differences in the acute bone metabolic response to exercise and areas of focally large changes in the metabolic bone response that might be representative of whole-joint dysfunction.
PMCID:9922526
PMID: 36031138
ISSN: 1522-9653
CID: 5579272

Gadolinium-free assessment of synovitis using diffusion tensor imaging

Sandford, Halston J C; MacKay, James W; Watkins, Lauren E; Gold, Garry E; Kogan, Feliks; Mazzoli, Valentina
The dynamic contrast-enhanced (DCE)-MRI parameter Ktrans can quantify the intensity of synovial inflammation (synovitis) in knees with osteoarthritis (OA), but requires the use of gadolinium-based contrast agent (GBCA). Diffusion tensor imaging (DTI) measures the diffusion of water molecules with parameters mean diffusivity (MD) and fractional anisotropy (FA), and has been proposed as a method to detect synovial inflammation without the use of GBCA. The purpose of this study is to (1) determine the ability of DTI to quantify the intensity of synovitis in OA by comparing MD and FA with our imaging gold standard Ktrans within the synovium and (2) compare DTI and DCE-MRI measures with the semi-quantitative grading of OA severity with the Kellgren-Lawrence (KL) and MRI Osteoarthritis Knee Score (MOAKS) systems, in order to assess the relationship between synovitis intensity and OA severity. Within the synovium, MD showed a significant positive correlation with Ktrans (r = 0.79, p < 0.001), while FA showed a significant negative correlation with Ktrans (r = -0.72, p = 0.0026). These results show that DTI is able to quantify the intensity of synovitis within the whole synovium without the use of exogenous contrast agent. Additionally, MD, FA, and Ktrans values did not vary significantly when knees were separated by KL grade (p = 0.15, p = 0.32, p = 0.41, respectively), while MD (r = 0.60, p = 0.018) and Ktrans (r = 0.62, p = 0.013) had a significant positive correlation and FA (r = -0.53, p = 0.043) had a negative correlation with MOAKS. These comparisons indicate that quantitative measures of the intensity of synovitis may provide information in addition to morphological assessment to evaluate OA severity. Using DTI to quantify the intensity of synovitis without GBCA may be helpful to facilitate a broader clinical assessment of the severity of OA.
PMCID:8688337
PMID: 34549476
ISSN: 1099-1492
CID: 5579212

A diffusion tensor-based method facilitating volumetric assessment of fiber orientations in skeletal muscle

Secondulfo, Laura; Hooijmans, Melissa T; Suskens, Joep J; Mazzoli, Valentina; Maas, Mario; Tol, Johannes L; Nederveen, Aart J; Strijkers, Gustav J
BACKGROUND:The purpose of this study was to develop a DTI-based method to quantitatively assess fiber angles and changes therein in leg muscles in order to facilitate longitudinal studies on muscle fiber architectural adaptations in healthy subjects. METHODS:The upper legs of five volunteers were scanned twice on the same day. The right lower legs of five volunteers were scanned twice with the ankle in three positions, i.e. -15° dorsiflexion, 0° neutral position, and 30° plantarflexion. The MRI protocols consisted of a noise scan, a 3-point mDixon scan and a DTI scan. Fiber-angle color maps were generated for four muscles in the upper legs and two muscles in the lower leg. Voxel-wise fiber angles (θ) were calculated from the angle between the principal eigenvector of the diffusion tensor and a reference line defined between the origo and insertion points of each muscle. Bland-Altman analysis, intraclass correlation coefficient (ICC), coefficient of variation (CV%), minimal detectable change (MDC), standard error (SE) and Friedman test were used for assessing the feasibility of this method and in order to have an indication of the repeatability and the sensitivity. RESULTS:Bland-Altman analysis showed good repeatability (CV%<10 and 0.7≤ICC≤0.9) with exception of the Tibialis Anterior (TA) muscle in dorsiflexion position(CV%: 12.2) and the Semitendinosus (ST) muscle (left leg) (CV%: 11.4). The best repeatability metrics were found for the SOL muscle in neutral position (CV%: 2.6). Changes in average θ in TA and SOL with ankle positions were observed in accordance with expected agonist and antagonist functions of both muscles. For example, for the anterior left compartment the change in fiber angle Δθ with respect to the neutral position Δθ = -1.6° ± 0.8° and 2.2° ± 2.8° (p = 0.008), for dorsiflexion and plantarflexion, respectively. CONCLUSION:Our method facilitates fast inspection and quantification of muscle fiber angles in the lower and upper leg muscles in rest and detection of changes in lower-leg muscle fiber angles with varying ankle angles.
PMCID:8794095
PMID: 35085267
ISSN: 1932-6203
CID: 5579232

Characterizing the transient response of knee cartilage to running: Decreases in cartilage T2 of female recreational runners

Crowder, Hollis A; Mazzoli, Valentina; Black, Marianne S; Watkins, Lauren E; Kogan, Feliks; Hargreaves, Brian A; Levenston, Marc E; Gold, Garry E
Cartilage transmits and redistributes biomechanical loads in the knee joint during exercise. Exercise-induced loading alters cartilage hydration and is detectable using quantitative magnetic resonance imaging (MRI), where T2 relaxation time (T2 ) is influenced by cartilage collagen composition, fiber orientation, and changes in the extracellular matrix. This study characterized short-term transient responses of healthy knee cartilage to running-induced loading using bilateral scans and image registration. Eleven healthy female recreational runners (33.73 ± 4.22 years) and four healthy female controls (27.25 ± 1.38 years) were scanned on a 3T GE MRI scanner with quantitative 3D double-echo in steady-state before running over-ground (runner group) or resting (control group) for 40 min. Subjects were scanned immediately post-activity at 5-min intervals for 60 min. T2 times were calculated for femoral, tibial, and patellar cartilage at each time point and analyzed using a mixed-effects model and Bonferroni post hoc. There were immediate decreases in T2 (mean ± SEM) post-run in superficial femoral cartilage of at least 3.3% ± 0.3% (p = .002) between baseline and Time 0 that remained for 25 min, a decrease in superficial tibial cartilage T2 of 2.9% ± 0.4% (p = .041) between baseline and Time 0, and a decrease in superficial patellar cartilage T2 of 3.6% ± 0.3% (p = .020) 15 min post-run. There were decreases in the medial posterior region of superficial femoral cartilage T2 of at least 5.3 ± 0.2% (p = .022) within 5 min post-run that remained at 60 min post-run. These results increase understanding of transient responses of healthy cartilage to repetitive, exercise-induced loading and establish preliminary recommendations for future definitive studies of cartilage response to running.
PMCID:8295402
PMID: 33483997
ISSN: 1554-527x
CID: 5579172

Effects of the Competitive Season and Off-Season on Knee Articular Cartilage in Collegiate Basketball Players Using Quantitative MRI: A Multicenter Study

Rubin, Elka B; Mazzoli, Valentina; Black, Marianne S; Young, Katherine; Desai, Arjun D; Koff, Matthew F; Sreedhar, Ashwin; Kogan, Feliks; Safran, Marc R; Vincentini, Dominic J; Knox, Katelin A; Yamada, Tomoo; McCabe, Andrew; Majumdar, Sharmila; Potter, Hollis G; Gold, Garry E
BACKGROUND:Injuries to the articular cartilage in the knee are common in jumping athletes, particularly high-level basketball players. Unfortunately, these are often diagnosed at a late stage of the disease process, after tissue loss has already occurred. PURPOSE/HYPOTHESIS:To evaluate longitudinal changes in knee articular cartilage and knee function in National Collegiate Athletic Association (NCAA) basketball players and their evolution over the competitive season and off-season. STUDY TYPE:Longitudinal, multisite cohort study. POPULATION:Thirty-two NCAA Division 1 athletes: 22 basketball players and 10 swimmers. FIELD STRENGTH/SEQUENCE:magnetization-prepared angle-modulated portioned k-space spoiled gradient-echo snapshots (MAPSS) sequence at 3T. ASSESSMENT:relaxation times to compare compositional cartilage changes between three timepoints: preseason 1, postseason 1, and preseason 2. Knee Osteoarthritis Outcome Scores (KOOS) were used to assess knee health. STATISTICAL TESTS:One-way variance model hypothesis test, general linear model, and chi-squared test. RESULTS:relaxation times following the competitive season and off-season. The basketball players had significantly lower KOOS measures in every domain compared with the swimmers: Pain (P < 0.05), Symptoms (P < 0.05), Function in Daily Living (P < 0.05), Function in Sport/Recreation (P < 0.05), and Quality of Life (P < 0.05). CONCLUSION:MRI can detect significant seasonal changes in the articular cartilage of basketball players and that there are regional differences in the articular cartilage that are indicative of basketball-specific stress on the femoral cartilage. This study demonstrates the potential of quantitative MRI to monitor global and regional cartilage health in athletes at risk of developing cartilage problems. LEVEL OF EVIDENCE:2 Technical Efficacy Stage: 2.
PMCID:8817387
PMID: 33763929
ISSN: 1522-2586
CID: 5579202

Assessment of quantitative [18F]Sodium fluoride PET measures of knee subchondral bone perfusion and mineralization in osteoarthritic and healthy subjects

Watkins, L; MacKay, J; Haddock, B; Mazzoli, V; Uhlrich, S; Gold, G; Kogan, F
OBJECTIVE:F]NaF uptake in subchondral bone of individuals with and without knee osteoarthritis (OA). METHODS:) were evaluated using the Hawkins 3-compartment model. Measures were compared between structurally normal-appearing bone regions and those with structural findings. RESULTS:, and extraction fraction were significantly different between Healthy subjects and subjects with OA. Between-group differences in metabolic parameters were observed both in regions where the OA group had degenerative changes as well as in regions that appeared structurally normal. CONCLUSIONS:F]NaF PET imaging can complement assessments of structural abnormalities observed on MRI.
PMCID:8159876
PMID: 33639259
ISSN: 1522-9653
CID: 5579182

Diffusion Tensor Imaging of Skeletal Muscle Contraction Using Oscillating Gradient Spin Echo

Mazzoli, Valentina; Moulin, Kevin; Kogan, Feliks; Hargreaves, Brian A; Gold, Garry E
Diffusion tensor imaging (DTI) measures water diffusion in skeletal muscle tissue and allows for muscle assessment in a broad range of neuromuscular diseases. However, current DTI measurements, typically performed using pulsed gradient spin echo (PGSE) diffusion encoding, are limited to the assessment of non-contracted musculature, therefore providing limited insight into muscle contraction mechanisms and contraction abnormalities. In this study, we propose the use of an oscillating gradient spin echo (OGSE) diffusion encoding strategy for DTI measurements to mitigate the effect of signal voids in contracted muscle and to obtain reliable diffusivity values. Two OGSE sequences with encoding frequencies of 25 and 50 Hz were tested in the lower leg of five healthy volunteers with relaxed musculature and during active dorsiflexion and plantarflexion, and compared with a conventional PGSE approach. A significant reduction of areas of signal voids using OGSE compared with PGSE was observed in the tibialis anterior for the scans obtained in active dorsiflexion and in the soleus during active plantarflexion. The use of PGSE sequences led to unrealistically elevated axial diffusivity values in the tibialis anterior during dorsiflexion and in the soleus during plantarflexion, while the corresponding values obtained using the OGSE sequences were significantly reduced. Similar findings were seen for radial diffusivity, with significantly higher diffusivity measured in plantarflexion in the soleus muscle using the PGSE sequence. Our preliminary results indicate that DTI with OGSE diffusion encoding is feasible in human musculature and allows to quantitatively assess diffusion properties in actively contracting skeletal muscle. OGSE holds great potential to assess microstructural changes occurring in the skeletal muscle during contraction, and for non-invasive assessment of contraction abnormalities in patients with muscle diseases.
PMCID:7917051
PMID: 33658976
ISSN: 1664-2295
CID: 5579192

Rapid volumetric gagCEST imaging of knee articular cartilage at 3 T: evaluation of improved dynamic range and an osteoarthritic population

Watkins, Lauren E; Rubin, Elka B; Mazzoli, Valentina; Uhlrich, Scott D; Desai, Arjun D; Black, Marianne; Ho, Gabe K; Delp, Scott L; Levenston, Marc E; Beaupré, Gary S; Gold, Garry E; Kogan, Feliks
Chemical exchange saturation transfer of glycosaminoglycans, gagCEST, is a quantitative MR technique that has potential for assessing cartilage proteoglycan content at field strengths of 7 T and higher. However, its utility at 3 T remains unclear. The objective of this work was to implement a rapid volumetric gagCEST sequence with higher gagCEST asymmetry at 3 T to evaluate its sensitivity to osteoarthritic changes in knee articular cartilage and in comparison with T2 and T measures. We hypothesize that gagCEST asymmetry at 3 T decreases with increasing severity of osteoarthritis (OA). Forty-two human volunteers, including 10 healthy subjects and 32 subjects with medial OA, were included in the study. Knee Injury and Osteoarthritis Outcome Scores (KOOS) were assessed for all subjects, and Kellgren-Lawrence grading was performed for OA volunteers. Healthy subjects were scanned consecutively at 3 T to assess the repeatability of the volumetric gagCEST sequence at 3 T. For healthy and OA subjects, gagCEST asymmetry and T2 and T relaxation times were calculated for the femoral articular cartilage to assess sensitivity to OA severity. Volumetric gagCEST imaging had higher gagCEST asymmetry than single-slice acquisitions (p = 0.015). The average scan-rescan coefficient of variation was 6.8%. There were no significant differences in average gagCEST asymmetry between younger and older healthy controls (p = 0.655) or between healthy controls and OA subjects (p = 0.310). T2 and T relaxation times were elevated in OA subjects (p < 0.001 for both) compared with healthy controls and both were moderately correlated with total KOOS scores (rho = -0.181 and rho = -0.332 respectively). The gagCEST technique developed here, with volumetric scan times under 10 min and high gagCEST asymmetry at 3 T, did not vary significantly between healthy subjects and those with mild-moderate OA. This further supports a limited utility for gagCEST imaging at 3 T for assessment of early changes in cartilage composition in OA.
PMCID:7347437
PMID: 32445515
ISSN: 1099-1492
CID: 5579142

Juvenile Idiopathic Arthritis: Diffusion-weighted MRI in the Assessment of Arthritis in the Knee

Barendregt, Anouk M; Mazzoli, Valentina; van Gulik, E Charlotte; Schonenberg-Meinema, Dieneke; Nassar-Sheikh Al Rashid, Amara; Nusman, Charlotte M; Dolman, Koert M; van den Berg, J Merlijn; Kuijpers, Taco W; Nederveen, Aart J; Maas, Mario; Hemke, Robert
Background Diffusion-weighted imaging (DWI) can depict the inflamed synovial membrane in arthritis. Purpose To study the diagnostic accuracy of DWI for the detection of arthritis compared with the clinical reference standard and to compare DWI to contrast material-enhanced MRI for the detection of synovial inflammation. Materials and Methods In this institutional review board-approved prospective study, 45 participants with juvenile idiopathic arthritis (JIA) or suspected of having JIA (seven boys, 38 girls; median age, 14 years [interquartile range, 12-16 years]) were included between December 2015 and December 2018. Study participants underwent pre- and postcontrast 3.0-T MRI of the knee with an additional DWI sequence. For the clinical reference standard, a multidisciplinary team determined the presence or absence of arthritis on the basis of clinical, laboratory, and imaging findings (excluding DWI). Two data sets were scored by two radiologists blinded to all clinical data; data set 1 contained pre- and postcontrast sequences (contrast-enhanced MRI), and data set 2 contained precontrast and DWI sequences (DWI). Diagnostic accuracy was determined by comparing the scores of the DWI data set to those of the clinical reference standard. Second, DWI was compared with contrast-enhanced MRI regarding detection of synovial inflammation. Results Sensitivity for detection of arthritis for DWI was 93% (13 of the 14 participants with arthritis were correctly classified with DWI; 95% confidence interval [CI]: 64%, 100%) and specificity was 81% (25 of 31 participants without arthritis were correctly classified with DWI; 95% CI: 62%, 92%). Scores for synovial inflammation at DWI and contrast-enhanced MRI agreed in 37 of 45 participants (82%), resulting in a sensitivity of 92% (12 of 13 participants; 95% CI: 62%, 100%) and specificity of 78% (25 of 32 participants; 95% CI: 60%, 90%) with DWI when contrast-enhanced MRI was considered the reference standard. Conclusion Diffusion-weighted imaging (DWI) was accurate in detecting arthritis in pediatric participants with juvenile idiopathic arthritis (JIA) or suspected of having JIA and showed agreement with contrast-enhanced MRI. The results indicate that DWI could replace contrast-enhanced MRI for imaging of synovial inflammation in this patient group. © RSNA, 2020 Online supplemental material is available for this article.
PMID: 32154774
ISSN: 1527-1315
CID: 5579132

T-mapping for assessing knee joint cartilage in children with juvenile idiopathic arthritis - feasibility and repeatability

Barendregt, Anouk M; Mazzoli, Valentina; van den Berg, J Merlijn; Kuijpers, Taco W; Maas, Mario; Nederveen, Aart J; Hemke, Robert
BACKGROUND:Ongoing arthritis in children with juvenile idiopathic arthritis (JIA) can result in cartilage damage. OBJECTIVE:and conventional MRI scores for disease activity. MATERIALS AND METHODS:with the juvenile arthritis MRI score. RESULTS:values and the juvenile arthritis MRI synovitis score (r=0.59, P=0.04). CONCLUSION:values were associated with the juvenile arthritis MRI synovitis score.
PMCID:7026305
PMID: 31707445
ISSN: 1432-1998
CID: 5579112