Academic Appointments

Honors & Awards

  • K99 - Quantitative assessment of early structural and functional changes in aging skeletal muscle, NIA/NIH (2021)
  • Junior Fellow, ISMRM (2020)
  • Rubicon grant, Dutch Organization for Research (2019)

All Publications

  • [18F]Sodium Fluoride PET-MRI Detects Increased Metabolic Bone Response to Whole-Joint Loading Stress in Osteoarthritic Knees. Osteoarthritis and cartilage Watkins, L. E., Haddock, B., MacKay, J. W., Baker, J., Uhlrich, S. D., Mazzoli, V., Gold, G. E., Kogan, F. 2022


    OBJECTIVE: Altered joint function is a hallmark of osteoarthritis (OA). Imaging techniques for joint function are limited, but [18F]sodium fluoride (NaF) PET-MRI may assess the acute joint response to loading stresses. [18F]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: In this prospective study, 10 participants with knee OA (59 ± 8 years; 8 female) were scanned twice consecutively using a PET-MR system and performed a one-legged squat exercise between scans. Changes in tracer uptake measures in 9 bone regions were compared between knees that did and did not exercise with a mixed-effects model. Areas of focally large changes in uptake between scans (ROIfocal, Delta SUVmax > 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: There was a significant increase in [18F]NaF uptake in OA exercised knees (SUV p < 0.001, Ki p = 0.002, K1 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.

    View details for DOI 10.1016/j.joca.2022.08.004

    View details for PubMedID 36031138

  • Generalizability of Deep Learning Segmentation Algorithms for Automated Assessment of Cartilage Morphology and MRI Relaxometry. Journal of magnetic resonance imaging : JMRI Schmidt, A. M., Desai, A. D., Watkins, L. E., Crowder, H. A., Black, M. S., Mazzoli, V., Rubin, E. B., Lu, Q., MacKay, J. W., Boutin, R. D., Kogan, F., Gold, G. E., Hargreaves, B. A., Chaudhari, A. S. 2022


    BACKGROUND: Deep learning (DL)-based automatic segmentation models can expedite manual segmentation yet require resource-intensive fine-tuning before deployment on new datasets. The generalizability of DL methods to new datasets without fine-tuning is not well characterized.PURPOSE: Evaluate the generalizability of DL-based models by deploying pretrained models on independent datasets varying by MR scanner, acquisition parameters, and subject population.STUDY TYPE: Retrospective based on prospectively acquired data.POPULATION: Overall test dataset: 59 subjects (26 females); Study 1: 5 healthy subjects (zero females), Study 2: 8 healthy subjects (eight females), Study 3: 10 subjects with osteoarthritis (eight females), Study 4: 36 subjects with various knee pathology (10 females).FIELD STRENGTH/SEQUENCE: A 3-T, quantitative double-echo steady state (qDESS).ASSESSMENT: Four annotators manually segmented knee cartilage. Each reader segmented one of four qDESS datasets in the test dataset. Two DL models, one trained on qDESS data and another on Osteoarthritis Initiative (OAI)-DESS data, were assessed. Manual and automatic segmentations were compared by quantifying variations in segmentation accuracy, volume, and T2 relaxation times for superficial and deep cartilage.STATISTICAL TESTS: Dice similarity coefficient (DSC) for segmentation accuracy. Lin's concordance correlation coefficient (CCC), Wilcoxon rank-sum tests, root-mean-squared error-coefficient-of-variation to quantify manual vs. automatic T2 and volume variations. Bland-Altman plots for manual vs. automatic T2 agreement. A P value<0.05 was considered statistically significant.RESULTS: DSCs for the qDESS-trained model, 0.79-0.93, were higher than those for the OAI-DESS-trained model, 0.59-0.79. T2 and volume CCCs for the qDESS-trained model, 0.75-0.98 and 0.47-0.95, were higher than respective CCCs for the OAI-DESS-trained model, 0.35-0.90 and 0.13-0.84. Bland-Altman 95% limits of agreement for superficial and deep cartilage T2 were lower for the qDESS-trained model, ±2.4msec and ±4.0msec, than the OAI-DESS-trained model, ±4.4msec and ±5.2msec.DATA CONCLUSION: The qDESS-trained model may generalize well to independent qDESS datasets regardless of MR scanner, acquisition parameters, and subject population.EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 1.

    View details for DOI 10.1002/jmri.28365

    View details for PubMedID 35852498

  • A diffusion tensor-based method facilitating volumetric assessment of fiber orientations in skeletal muscle. PloS one Secondulfo, L., Hooijmans, M. T., Suskens, J. J., Mazzoli, V., Maas, M., Tol, J. L., Nederveen, A. J., Strijkers, G. J. 1800; 17 (1): e0261777


    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 (theta) 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 theta 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 Deltatheta with respect to the neutral position Deltatheta = -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.

    View details for DOI 10.1371/journal.pone.0261777

    View details for PubMedID 35085267

  • Gadolinium-free assessment of synovitis using diffusion tensor imaging. NMR in biomedicine Sandford, H. J., MacKay, J. W., Watkins, L. E., Gold, G. E., Kogan, F., Mazzoli, V. 2021: e4614


    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.

    View details for DOI 10.1002/nbm.4614

    View details for PubMedID 34549476

  • Assessment of Quantitative [18F]Sodium Fluoride PET Measures of Knee Subchondral Bone Perfusion and Mineralization in Osteoarthritic and Healthy Subjects. Osteoarthritis and cartilage Watkins, L., MacKay, J., Haddock, B., Mazzoli, V., Uhlrich, S., Gold, G., Kogan, F. 2021


    OBJECTIVE: Molecular information derived from dynamic [18F]sodium fluoride ([18F]NaF) PET imaging holds promise as a quantitative marker of bone metabolism. The objective of this work was to evaluate physiological mechanisms of [18F]NaF uptake in subchondral bone of individuals with and without knee osteoarthritis (OA).METHODS: Eleven healthy volunteers and twenty OA subjects were included. Both knees of all subjects were scanned simultaneously using a 3T hybrid PET/MRI system. MRI MOAKS assessment was performed to score the presence and size of osteophytes, bone marrow lesions, and cartilage lesions. Subchondral bone kinetic parameters of bone perfusion (K1), tracer extraction fraction, and total tracer uptake into bone (Ki) were evaluated using the Hawkins 3-compartment model. Measures were compared between structurally normal-appearing bone regions and those with structural findings.RESULTS: Mean and maximum SUV and kinetic parameters Ki, K1, 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: Results suggest that bone metabolism is altered in OA subjects, including bone regions with and without structural findings, compared to healthy subjects. Kinetic parameters of [18F]NaF uptake in subchondral bone show potential to quantitatively evaluate the role of bone physiology in OA initiation and progression. Objective measures of bone metabolism from [18F]NaF PET imaging can complement assessments of structural abnormalities observed on MRI.

    View details for DOI 10.1016/j.joca.2021.02.563

    View details for PubMedID 33639259

  • Characterizing the transient response of knee cartilage to running: Decreases in cartilage T2 of female recreational runners. Journal of orthopaedic research : official publication of the Orthopaedic Research Society Crowder, H. A., Mazzoli, V. n., Black, M. S., Watkins, L. E., Kogan, F. n., Hargreaves, B. A., Levenston, M. E., Gold, G. E. 2021


    Cartilage transmits and redistributes biomechanical loads in the knee joint during exercise. Exercise-induced loading alters cartilage hydration and is detectable using quantitative MRI, where T2 relaxation time (T2 ) is influenced by cartilage collagen composition, fiber orientation, and changes in 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 qDESS before running over-ground (runner group) or resting (control group) for 40 minutes. Subjects were scanned immediately post-activity at five-minute intervals for 60 minutes. 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=0.002) between baseline and Time 0 that remained for 25 minutes, a decrease in superficial tibial cartilage T2 of 2.9±0.4% (P=0.041) between baseline and Time 0, and a decrease in superficial patellar cartilage T2 of 3.6±0.3% (P=0.020) 15 minutes post-run. There were decreases in the medial posterior region of superficial femoral cartilage T2 of at least 5.3±0.2% (P=0.022) within five minutes post-run that remained at 60 minutes post-run. Clinical Significance: 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. This article is protected by copyright. All rights reserved.

    View details for DOI 10.1002/jor.24994

    View details for PubMedID 33483997

  • Effects of the Competitive Season and Off-Season on Knee Articular Cartilage in Collegiate Basketball Players Using Quantitative MRI: A Multicenter Study. Journal of magnetic resonance imaging : JMRI Rubin, E. B., Mazzoli, V. n., Black, M. S., Young, K. n., Desai, A. D., Koff, M. F., Sreedhar, A. n., Kogan, F. n., Safran, M. R., Vincentini, D. J., Knox, K. A., Yamada, T. n., McCabe, A. n., Majumdar, S. n., Potter, H. G., Gold, G. E. 2021


    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.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.Longitudinal, multisite cohort study.Thirty-two NCAA Division 1 athletes: 22 basketball players and 10 swimmers.Bilateral magnetic resonance imaging (MRI) using a combined T1ρ and T2 magnetization-prepared angle-modulated portioned k-space spoiled gradient-echo snapshots (MAPSS) sequence at 3T.We calculated T2 and T1ρ 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.One-way variance model hypothesis test, general linear model, and chi-squared test.In the femoral articular cartilage of all athletes, we saw a global decrease in T2 and T1ρ relaxation times during the competitive season (all P < 0.05) and an increase in T2 and T1ρ relaxation times during the off-season (all P < 0.05). In the basketball players' femoral cartilage, the anterior and central compartments respectively had the highest T2 and T1ρ 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).Our results indicate that T2 and T1ρ 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.2 Technical Efficacy Stage: 2.

    View details for DOI 10.1002/jmri.27610

    View details for PubMedID 33763929

  • Diffusion Tensor Imaging of Skeletal Muscle Contraction Using Oscillating Gradient Spin Echo. Frontiers in neurology Mazzoli, V. n., Moulin, K. n., Kogan, F. n., Hargreaves, B. A., Gold, G. E. 2021; 12: 608549


    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.

    View details for DOI 10.3389/fneur.2021.608549

    View details for PubMedID 33658976

    View details for PubMedCentralID PMC7917051

  • Evaluating the Relationship between Dynamic Na[F-18]F-Uptake Parameters and MRI Knee Osteoarthritic Findings Watkins, L., MacKay, J., Haddock, B., Mazzoli, V., Uhlrich, S., Gold, G., Kogan, F. SOC NUCLEAR MEDICINE INC. 2020
  • Juvenile Idiopathic Arthritis: Diffusion-weighted MRI in the Assessment of Arthritis in the Knee. Radiology Barendregt, A. M., Mazzoli, V., van Gulik, E. C., Schonenberg-Meinema, D., Nassar-Sheikh Al Rashid, A., Nusman, C. M., Dolman, K. M., van den Berg, J. M., Kuijpers, T. W., Nederveen, A. J., Maas, M., Hemke, R. 2020: 191685


    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.

    View details for DOI 10.1148/radiol.2020191685

    View details for PubMedID 32154774

  • Rapid volumetric gagCEST imaging of knee articular cartilage at 3 T: evaluation of improved dynamic range and an osteoarthritic population. NMR in biomedicine Watkins, L. E., Rubin, E. B., Mazzoli, V. n., Uhlrich, S. D., Desai, A. D., Black, M. n., Ho, G. K., Delp, S. L., Levenston, M. E., Beaupré, G. S., Gold, G. E., Kogan, F. n. 2020: e4310


    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 T1ρ 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 T1ρ 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 T1ρ 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.

    View details for DOI 10.1002/nbm.4310

    View details for PubMedID 32445515

  • T1rho-mapping for assessing knee joint cartilage in children with juvenile idiopathic arthritis - feasibility and repeatability. Pediatric radiology Barendregt, A. M., Mazzoli, V., van den Berg, J. M., Kuijpers, T. W., Maas, M., Nederveen, A. J., Hemke, R. 2019


    BACKGROUND: Ongoing arthritis in children with juvenile idiopathic arthritis (JIA) can result in cartilage damage.OBJECTIVE: To study the feasibility and repeatability of T1rho for assessing knee cartilage in JIA and also to describe T1rho values and study correlation between T1rho and conventional MRI scores for disease activity.MATERIALS AND METHODS: Thirteen children with JIA or suspected JIA underwent 3-tesla (T) knee MRI that included conventional sequences and a T1rho sequence. Segmentation of knee cartilage was carried out on T1rho images. We used intraclass correlation coefficient to study the repeatability of segmentation in a subset of five children. We used the juvenile arthritis MRI scoring system to discriminate inflamed from non-inflamed knees. The Mann-Whitney U and Spearman correlation compared T1rho between children with and without arthritis on MRI and correlated T1rho with the juvenile arthritis MRI score.RESULTS: All children successfully completed the MRI examination. No images were excluded because of poor quality. Repeatability of T1rho measurement had an intraclass correlation coefficient (ICC) of 0.99 (P<0.001). We observed no structural cartilage damage and found no differences in T1rho between children with (n=7) and without (n=6) inflamed knees (37.8ms vs. 31.7ms, P=0.20). However, we observed a moderate correlation between T1rho values and the juvenile arthritis MRI synovitis score (r=0.59, P=0.04).CONCLUSION: This pilot study suggests that T1rho is a feasible and repeatable quantitative imaging technique in children. T1rho values were associated with the juvenile arthritis MRI synovitis score.

    View details for DOI 10.1007/s00247-019-04557-4

    View details for PubMedID 31707445

  • Crossing muscle fibers of the human tongue resolved in vivo using constrained spherical deconvolution JOURNAL OF MAGNETIC RESONANCE IMAGING Voskuilen, L., Mazzoli, V., Oudeman, J., Balm, A. M., van der Heijden, F., Froeling, M., de Win, M. L., Strijkers, G. J., Smeele, L. E., Nederveen, A. J. 2019; 50 (1): 96–105

    View details for DOI 10.1002/jmri.26609

    View details for Web of Science ID 000471831600009

  • A noninvasive MRI based approach to estimate the mechanical properties of human knee ligaments JOURNAL OF THE MECHANICAL BEHAVIOR OF BIOMEDICAL MATERIALS Naghibi, H., Mazzoli, V., Gijsbertse, K., Hannink, G., Sprengers, A., Janssen, D., Van den Boogaard, T., Verdonschot, N. 2019; 93: 43–51
  • A noninvasive MRI based approach to estimate the mechanical properties of human knee ligaments. Journal of the mechanical behavior of biomedical materials Naghibi, H., Mazzoli, V., Gijsbertse, K., Hannink, G., Sprengers, A., Janssen, D., Van den Boogaard, T., Verdonschot, N. 2019; 93: 43–51


    Characterization of the main tibiofemoral ligaments is an essential step in developing patient-specific computational models of the knee joint for personalized surgery pre-planning. Tensile tests are commonly performed in-vitro to characterize the mechanical stiffness and rupture force of the knee ligaments which makes the technique unsuitable for in-vivo application. The time required for the limited noninvasive approaches for properties estimation based on knee laxity remained the main obstacle in clinical implementation. Magnetic resonance imaging (MRI) technique can be a platform to noninvasively assess the knee ligaments. In this study the aim was to explore the potential role of quantitative MRI and dimensional properties, in characterizing the mechanical properties of the main tibiofemoral ligaments. After MR scanning of six cadaveric legs, all 24 main tibiofemoral bone-ligaments-bone specimens were tested in vitro. During the tensile test cross sectional area of the specimens was captured using ultrasound and force-displacement curve was extracted. Digital image correlation technique was implemented to check the strain behavior of the specimen and rupture region and to assure the fixation of ligament bony block during the test. The volume of the specimen was measured using manual segmentation data, and quantitative MR parameters as T2*, T1rho, and T2 were calculated. Linear mixed statistical models for repeated measures were used to examine the association of MRI parameters and dimensional measurements with the mechanical properties (stiffness and rupture force). The results shows that while the mechanical properties were mostly correlated to the volume, inclusion of the MR parameters increased the correlation strength for stiffness (R2  0.48) and partial rupture force (R2 = 0.53). Inclusion of ligament type in the statistical analysis enhanced the correlation of mechanical properties with MR parameters and volume as for stiffness (R2 = 0.60) and partial rupture (R2 = 0.57). In conclusion, this study revealed the potentials in using quantitative MR parameters, T1rho, T2 and T2*, combined with specimen volume to estimate the essential mechanical properties of all main tibiofemoral ligaments required for subject-specific computational modeling of human knee joint.

    View details for PubMedID 30769233

  • Accelerated 4D phase contrast MRI in skeletal muscle contraction. Magnetic resonance in medicine Mazzoli, V., Gottwald, L. M., Peper, E. S., Froeling, M., Coolen, B. F., Verdonschot, N., Sprengers, A. M., van Ooij, P., Strijkers, G. J., Nederveen, A. J. 2018


    3D time-resolved (4D) phase contrast MRI can be used to study muscle contraction. However, 3D coverage with sufficient spatiotemporal resolution can only be achieved by interleaved acquisitions during many repetitions of the motion task, resulting in long scan times. The aim of this study was to develop a compressed sensing accelerated 4D phase contrast MRI technique for quantification of velocities and strain rate of the muscles in the lower leg during active plantarflexion/dorsiflexion.Nine healthy volunteers were scanned during active dorsiflexion/plantarflexion task. For each volunteer, we acquired a reference scan, as well as 4 different accelerated scans (k-space undersampling factors: 3.14X, 4.09X, 4.89X, and 6.41X) obtained using Cartesian Poisson disk undersampling schemes. The data was reconstructed using a compressed sensing pipeline. For each scan, velocity and strain rate values were quantified in the gastrocnemius lateralis, gastrocnemius medialis, tibialis anterior, and soleus.No significant differences in velocity values were observed as a function acceleration factor in the investigated muscles. The strain rate calculation resulted in one positive (s+) and one negative (s-) eigenvalue, whereas the third eigenvalue (s3) was consistently 0 for all the acquisitions. No significant differences were observed for the strain rate eigenvalues as a function of acceleration factor.Data undersampling combined with compressed sensing reconstruction allowed obtainment of time-resolved phase contrast acquisitions with 3D coverage and quantitative information comparable to the reference scan. The 3D sensitivity of the method can help in understanding the connection between muscle architecture and muscle function in future studies.

    View details for DOI 10.1002/mrm.27158

    View details for PubMedID 29508449

  • An advanced magnetic resonance imaging perspective on the etiology of deep tissue injury. Journal of applied physiology (Bethesda, Md. : 1985) Nelissen, J. L., Traa, W. A., de Boer, H. H., de Graaf, L., Mazzoli, V., Savci-Heijink, C. D., Nicolay, K., Froeling, M., Bader, D. L., Nederveen, A. J., Oomens, C. W., Strijkers, G. J. 2018


    Early diagnosis of deep tissue injury remains problematic due to the complicated and multi-factorial nature of damage induction, and the many processes involved in damage development and recovery. In this paper we present a comprehensive assessment of deep tissue injury development and remodeling in a rat model by multi-parametric magnetic resonance imaging (MRI) and histopathology. The tibialis anterior muscle of rats was subjected to mechanical deformation for 2 h. Multi-parametric in vivo MRI, consisting of T2, T2∗, mean diffusivity (MD), and angiography measurements, was applied before, during, and directly after indentation, as well as at several time points during a 14 days follow-up. MRI readouts were linked to histological analyses of the damaged tissue. The results showed dynamic change in various MRI parameters, reflecting the histopathological status of the tissue during damage induction and repair. Increased T2corresponded with edema, muscle cell damage, and inflammation. T2∗ was related to tissue perfusion, hemorrhage, and inflammation. MD increase and decrease reported on the tissue's microstructural integrity and reflected muscle degeneration, edema, as well as fibrosis. Angiography provided information on blockage of blood flow during deformation. Our results indicate that the effects of a single damage causing event of only 2 h deformation were present up to 14 days. The initial tissue response to deformation, as observed by MRI, starts at the edge of the indentation. The quantitative MRI readouts provided distinct and complementary information on the extent, temporal evolution, and microstructural basis of deep tissue injury related muscle damage.

    View details for DOI 10.1152/japplphysiol.00891.2017

    View details for PubMedID 29494291

  • Accelerated 4D self-gated MRI of tibiofemoral kinematics. NMR in biomedicine Mazzoli, V., Schoormans, J., Froeling, M., Sprengers, A. M., Coolen, B. F., Verdonschot, N., Strijkers, G. J., Nederveen, A. J. 2017; 30 (11)


    Anatomical (static) magnetic resonance imaging (MRI) is the most useful imaging technique for the evaluation and assessment of internal derangement of the knee, but does not provide dynamic information and does not allow the study of the interaction of the different tissues during motion. As knee pain is often only experienced during dynamic tasks, the ability to obtain four-dimensional (4D) images of the knee during motion could improve the diagnosis and provide a deeper understanding of the knee joint. In this work, we present a novel approach for dynamic, high-resolution, 4D imaging of the freely moving knee without the need for external triggering. The dominant knee of five healthy volunteers was scanned during a flexion/extension task. To evaluate the effects of non-uniform motion and poor coordination skills on the quality of the reconstructed images, we performed a comparison between fully free movement and movement instructed by a visual cue. The trigger signal for self-gating was extracted using principal component analysis (PCA), and the images were reconstructed using a parallel imaging and compressed sensing reconstruction pipeline. The reconstructed 4D movies were scored for image quality and used to derive bone kinematics through image registration. Using our method, we were able to obtain 4D high-resolution movies of the knee without the need for external triggering hardware. The movies obtained with and without instruction did not differ significantly in terms of image scoring and quantitative values for tibiofemoral kinematics. Our method showed to be robust for the extraction of the self-gating signal even for uninstructed motion. This can make the technique suitable for patients who, as a result of pain, may find it difficult to comply exactly with instructions. Furthermore, bone kinematics can be derived from accelerated MRI without the need for additional hardware for triggering.

    View details for DOI 10.1002/nbm.3791

    View details for PubMedID 28873255

  • Assessment of passive muscle elongation using Diffusion Tensor MRI: Correlation between fiber length and diffusion coefficients NMR IN BIOMEDICINE Mazzoli, V., Oudeman, J., Nicolay, K., Maas, M., Verdonschot, N., Sprengers, A. M., Nederveen, A. J., Froeling, M., Strijkers, G. J. 2016; 29 (12): 1813-1824


    In this study we investigated the changes in fiber length and diffusion parameters as a consequence of passive lengthening and stretching of the calf muscles. We hypothesized that changes in radial diffusivity (RD) are caused by changes in the muscle fiber cross sectional area (CSA) as a consequence of lengthening and shortening of the muscle. Diffusion Tensor MRI (DT-MRI) measurements were made twice in five healthy volunteers, with the foot in three different positions (30° plantarflexion, neutral position and 15° dorsiflexion). The muscles of the calf were manually segmented on co-registered high resolution anatomical scans, and maps of RD and axial diffusivity (AD) were reconstructed from the DT-MRI data. Fiber tractography was performed and mean fiber length was calculated for each muscle group. Significant negative correlations were found between the changes in RD and changes in fiber length in the dorsiflexed and plantarflexed positions, compared with the neutral foot position. Changes in AD did not correlate with changes in fiber length. Assuming a simple cylindrical model with constant volume for the muscle fiber, the changes in the muscle fiber CSA were calculated from the changes in fiber length. In line with our hypothesis, we observed a significant positive correlation of the CSA with the measured changes in RD. In conclusion, we showed that changes in diffusion coefficients induced by passive muscle stretching and lengthening can be explained by changes in muscle CSA, advancing the physiological interpretation of parameters derived from skeletal muscle DT-MRI.

    View details for DOI 10.1002/nbm.3661

    View details for Web of Science ID 000389141000015

    View details for PubMedID 27862471

  • A novel diffusion-tensor MRI approach for skeletal muscle fascicle length measurements. Physiological reports Oudeman, J., Mazzoli, V., Marra, M. A., Nicolay, K., Maas, M., Verdonschot, N., Sprengers, A. M., Nederveen, A. J., Strijkers, G. J., Froeling, M. 2016; 4 (24)


    Musculoskeletal (dys-)function relies for a large part on muscle architecture which can be obtained using Diffusion-Tensor MRI (DT-MRI) and fiber tractography. However, reconstructed tracts often continue along the tendon or aponeurosis when using conventional methods, thus overestimating fascicle lengths. In this study, we propose a new method for semiautomatic segmentation of tendinous tissue using tract density (TD). We investigated the feasibility and repeatability of this method to quantify the mean fascicle length per muscle. Additionally, we examined whether the method facilitates measuring changes in fascicle length of lower leg muscles with different foot positions. Five healthy subjects underwent two DT-MRI scans of the right lower leg, with the foot in 15° dorsiflexion, neutral, and 30° plantarflexion positions. Repeatability of fascicle length measurements was assessed using Bland-Altman analysis. Changes in fascicle lengths between the foot positions were tested using a repeated multivariate analysis of variance (MANOVA). Bland-Altman analysis showed good agreement between repeated measurements. The coefficients of variation in neutral position were 8.3, 16.7, 11.2, and 10.4% for soleus (SOL), fibularis longus (FL), extensor digitorum longus (EDL), and tibialis anterior (TA), respectively. The plantarflexors (SOL and FL) showed significant increase in fascicle length from plantarflexion to dorsiflexion, whereas the dorsiflexors (EDL and TA) exhibited a significant decrease. The use of a tract density for semiautomatic segmentation of tendinous structures provides more accurate estimates of the mean fascicle length than traditional fiber tractography methods. The method shows moderate to good repeatability and allows for quantification of changes in fascicle lengths due to passive stretch.

    View details for DOI 10.14814/phy2.13012

    View details for PubMedID 28003562

    View details for PubMedCentralID PMC5210383

  • Water and fat separation in real-time MRI of joint movement with phase-sensitive bSSFP. Magnetic resonance in medicine Mazzoli, V., Nederveen, A. J., Oudeman, J., Sprengers, A., Nicolay, K., Strijkers, G. J., Verdonschot, N. 2016


    To introduce a method for obtaining fat-suppressed images in real-time MRI of moving joints at 3 Tesla (T) using a bSSFP sequence with phase detection to enhance visualization of soft tissue structures during motion.The wrist and knee of nine volunteers were imaged with a real-time bSSFP sequence while performing dynamic tasks. For appropriate choice of sequence timing parameters, water and fat pixels showed an out-of-phase behavior, which was exploited to reconstruct water and fat images. Additionally, a 2-point Dixon sequence was used for dynamic imaging of the joints, and resulting water and fat images were compared with our proposed method.The joints could be visualized with good water-fat separation and signal-to-noise ratio (SNR), while maintaining a relatively high temporal resolution (5 fps in knee imaging and 10 fps in wrist imaging). The proposed method produced images of moving joints with higher SNR and higher image quality when compared with the Dixon method.Water-fat separation is feasible in real-time MRI of moving knee and wrist at 3 T. PS-bSSFP offers movies with higher SNR and higher diagnostic quality when compared with Dixon scans. Magn Reson Med 78:58-68, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

    View details for DOI 10.1002/mrm.26341

    View details for PubMedID 27417271

  • Diffusion-Prepared Neurography of the Brachial Plexus With a Large Field-of-View at 3T JOURNAL OF MAGNETIC RESONANCE IMAGING Oudeman, J., Coolen, B. F., Mazzoli, V., Maas, M., Verhamme, C., Brink, W. M., Webb, A. G., Strijkers, G. J., Nederveen, A. J. 2016; 43 (3): 644-654


    To study diffusion-prepared neurography optimized for a large field-of-view (FOV) to include the neck and both shoulders. In a large FOV poor homogeneity of the magnetic field (B0 ) often leads to poor image quality and possibly to poor diagnostic accuracy. The aim was therefore to find an optimal (combination of) shimming method(s) for diffusion-prepared neurography in a large FOV.A 3D diffusion-prepared sequence with a large FOV was tested with and without the use of a susceptibility-matched pillow combined with image-based (IB) or standard shimming in six healthy volunteers on a 3T system. B0 , B1 , signal to noise ratio (SNR), and contrast to noise ratio (CNR) were compared between all protocols. Additionally, nerve visibility, fat suppression, artifacts, and overall image quality were ordinally (5-point scale) assessed by two readers. Furthermore, correlations between B0 and B1 (offset and variation) and SNR, CNR, and image quality were explored.The use of the susceptibility-matched pillow led to a 43% reduction of B0 variation over the brachial plexus compared to the situation without a pillow (P < 0.05). The combination of the pillow with IB-shimming and the optimized diffusion-prepared sequence resulted in good nerve visibility, good fat suppression, no artifacts that would hinder clinical diagnosis, and a good overall quality (median scores ≥4). Reducing B0 variation was associated with SNR, CNR, and the above-mentioned scored features (P < 0.05).The use of a susceptibility-matched pillow in combination with IB-shimming enables robust and high-quality neurography of the complete brachial plexus.

    View details for DOI 10.1002/jmri.25025

    View details for Web of Science ID 000373000300013

    View details for PubMedID 26251015