Feliks Kogan

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

  Abstract

  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

• Non-contrast MRI of synovitis in the knee using quantitative DESS. European radiology Thoenen, J., Stevens, K. J., Turmezei, T. D., Chaudhari, A., Watkins, L. E., McWalter, E. J., Hargreaves, B. A., Gold, G. E., MacKay, J. W., Kogan, F. 2021

  Abstract

  OBJECTIVES: To determine whether synovitis graded by radiologists using hybrid quantitative double-echo in steady-state (qDESS) images can be utilized as a non-contrast approach to assess synovitis in the knee, compared against the reference standard of contrast-enhanced MRI (CE-MRI).METHODS: Twenty-two knees (11 subjects) with moderate to severe osteoarthritis (OA) were scanned using CE-MRI, qDESS with a high diffusion weighting (qDESSHigh), and qDESS with a low diffusion weighting (qDESSLow). Four radiologists graded the overall impression of synovitis, their diagnostic confidence, and regional grading of synovitis severity at four sites (suprapatellar pouch, intercondylar notch, and medial and lateral peripatellar recesses) in the knee using a 4-point scale. Agreement between CE-MRI and qDESS, inter-rater agreement, and intra-rater agreement were assessed using a linearly weighted Gwet's AC2.RESULTS: Good agreement was seen between CE-MRI and both qDESSLow (AC2=0.74) and qDESSHigh (AC2=0.66) for the overall impression of synovitis, but both qDESS sequences tended to underestimate the severity of synovitis compared to CE-MRI. Good inter-rater agreement was seen for both qDESS sequences (AC2=0.74 for qDESSLow, AC2=0.64 for qDESSHigh), and good intra-rater agreement was seen for both sequences as well (qDESSLow AC2=0.78, qDESSHigh AC2=0.80). Diagnostic confidence was moderate to high for qDESSLow (mean=2.36) and slightly less than moderate for qDESSHigh (mean=1.86), compared to mostly high confidence for CE-MRI (mean=2.73).CONCLUSIONS: qDESS shows potential as an alternative MRI technique for assessing the severity of synovitis without the use of a gadolinium-based contrast agent.KEY POINTS: The use of the quantitative double-echo in steady-state (qDESS) sequence for synovitis assessment does not require the use of a gadolinium-based contrast agent. Preliminary results found that low diffusion-weighted qDESS (qDESSLow) shows good agreement to contrast-enhanced MRI for characterization of the severity of synovitis, with a relative bias towards underestimation of severity. Preliminary results also found that qDESSLow shows good inter- and intra-rater agreement for the depiction of synovitis, particularly for readers experienced with the sequence.

  View details for DOI 10.1007/s00330-021-08025-2

  View details for PubMedID 33993332

• [18F]NaF PET-MRI provides direct in-vivo evidence of the association between bone metabolic activity and adjacent synovitis in knee osteoarthritis: a cross-sectional study. Osteoarthritis and cartilage MacKay, J., Watkins, L., Gold, G., Kogan, F. 2021

  Abstract

  OBJECTIVE: Synovitis is hypothesized to play a role in the development and growth of osteophytes. Our objectives were to use hybrid positron emission tomography-magnetic resonance imaging (PET-MRI) to (1) determine whether synovitis adjacent to peripheral bone subregions with increased metabolic activity is greater than adjacent to regions without increased metabolic activity and (2) assess the association between subregional bone metabolic activity and adjacent synovitis.DESIGN: We recruited 11 participants (22 knees) with a diagnosis of OA in at least one knee. Simultaneous bilateral knee PET-MRI was performed. We quantified bone metabolic activity using the radiotracer [18F]sodium fluoride ([18F]NaF) with calculation of maximum standardized uptake values (SUVmax). Synovitis was quantified using dynamic contrast-enhanced MRI with calculation of Ktrans. Bone subregions were coded as osteophyte (OP), focal increased [18F]NaF uptake without osteophyte (FIU), or normal (no osteophyte or FIU). We used robust linear mixed effects models to assess differences in adjacent Ktrans between different subregion types and to assess association between Ktrans and adjacent SUVmax.RESULTS: 94 OPs were detected (59 MOAKS grade 1, 30 grade 2, 5 grade 3), along with 28 FIU and 18 normal subregions. Ktrans was higher adjacent to FIU (adjusted mean[95% CI] = 0.06[0.03,0.09]) and OPs (0.08[0.05,0.11]) when compared to normal bone subregions (0.03[0.00,0.09]). PET SUVmax was positively associated with adjacent Ktrans (beta[95% CI]=0.018[0.008,0.027]).CONCLUSIONS: Synovitis is more intense adjacent to peripheral bone regions with increased metabolic activity than those without, although there is some overlap. Subregional bone metabolic activity is positively associated with intensity of adjacent synovitis.

  View details for DOI 10.1016/j.joca.2021.04.014

  View details for PubMedID 33975018

• Assessment of acute bone loading in humans using [18F]NaF PET/MRI. European journal of nuclear medicine and molecular imaging Haddock, B., Fan, A. P., Uhlrich, S. D., Jorgensen, N. R., Suetta, C., Gold, G. E., Kogan, F. 2019

  Abstract

  PURPOSE: The acute effect of loading on bone tissue and physiology can offer important information with regard to joint function in diseases such as osteoarthritis. Imaging studies using [18F]-sodium fluoride ([18F]NaF) have found changes in tracer kinetics in animals after subjecting bones to strain, indicating an acute physiological response. The aim of this study is to measure acute changes in NaF uptake in human bone due to exercise-induced loading.METHODS: Twelve healthy subjects underwent two consecutive 50-min [18F]NaF PET/MRI examinations of the knees, one baseline followed by one post-exercise scan. Quantification of tracer kinetics was performed using an image-derived input function from the popliteal artery. For both scans, kinetic parameters of KiNLR, K1, k2, k3, and blood volume were mapped parametrically using nonlinear regression with the Hawkins model. The kinetic parameters along with mean SUV and SUVmax were compared between the pre- and post-exercise examinations. Differences in response to exercise were analysed between bone tissue types (subchondral, cortical, and trabecular bone) and between regional subsections of knee subchondral bone.RESULTS: Exercise induced a significant (p<<0.001) increase in [18F]NaF uptake in all bone tissues in both knees, with mean SUV increases ranging from 47% in trabecular bone tissue to 131% in subchondral bone tissue. Kinetic parameters involving vascularization (K1 and blood volume) increased, whereas the NaF extraction fraction [k3/(k2+k3)] was reduced.CONCLUSIONS: Bone loading induces an acute response in bone physiology as quantified by [18F]NaF PET kinetics. Dynamic imaging after bone loading using [18F]NaF PET is a promising diagnostic tool in bone physiology and imaging of biomechanics.

  View details for DOI 10.1007/s00259-019-04424-2

  View details for PubMedID 31385012

• Quantitative imaging of bone–cartilage interactions in ACL-injured patients with PET–MRI Osteoarthritis and Cartilage Kogan, F., Fan, A., Monu, U. D., Iagaru, A., Hargreaves, B., Gold, G. 2018; 26 (6): 790-796

  Abstract

  To investigate changes in bone metabolism by positron emission tomography (PET), as well as spatial relationships between bone metabolism and magnetic resonance imaging (MRI) quantitative markers of early cartilage degradation, in anterior cruciate ligament (ACL)-reconstructed knees.Both knees of 15 participants with unilateral reconstructed ACL tears and unaffected contralateral knees were scanned using a simultaneous 3.0T PET-MRI system following injection of 18F-sodium fluoride (18F-NaF). The maximum pixel standardized uptake value (SUVmax) in the subchondral bone and the average T2 relaxation time in cartilage were measured in each knee in eight knee compartments. We tested differences in SUVmax and cartilage T2 relaxation times between the ACL-injured knee and the contralateral control knee as well as spatial relationships between these bone and cartilage changes.Significantly increased subchondral bone 18F-NaF SUVmax and cartilage T2 times were observed in the ACL-reconstructed knees (median [inter-quartile-range (IQR)]: 5.0 [5.8], 36.8 [3.6] ms) compared to the contralateral knees (median [IQR]: 1.9 [1.4], 34.4 [3.8] ms). A spatial relationship between the two markers was also seen. Using the contralateral knee as a control, we observed a significant correlation of r = 0.59 between the difference in subchondral bone SUVmax (between injured and contralateral knees) and the adjacent cartilage T2 (between the two knees) [P < 0.001], with a slope of 0.49 ms/a.u. This correlation and slope were higher in deep layers (r = 0.73, slope = 0.60 ms/a.u.) of cartilage compared to superficial layers (r = 0.40, slope = 0.43 ms/a.u.).18F-NaF PET-MR imaging enables detection of increased subchondral bone metabolism in ACL-reconstructed knees and may serve as an important marker of early osteoarthritis (OA) progression. Spatial relationships observed between early OA changes across bone and cartilage support the need to study whole-joint disease mechanisms in OA.

  View details for DOI 10.1016/j.joca.2018.04.001

• Simultaneous bilateral-knee MR imaging. Magnetic resonance in medicine Kogan, F. n., Levine, E. n., Chaudhari, A. S., Monu, U. D., Epperson, K. n., Oei, E. H., Gold, G. E., Hargreaves, B. A. 2018; 80 (2): 529–37

  Abstract

  To demonstrate and evaluate the scan time and quantitative accuracy of simultaneous bilateral-knee imaging compared with single-knee acquisitions.Hardware modifications and safety testing was performed to enable MR imaging with two 16-channel flexible coil arrays. Noise covariance and sensitivity-encoding g-factor maps for the dual-coil-array configuration were computed to evaluate coil cross-talk and noise amplification. Ten healthy volunteers were imaged on a 3T MRI scanner with both dual-coil-array bilateral-knee and single-coil-array single-knee configurations. Two experienced musculoskeletal radiologists compared the relative image quality between blinded image pairs acquired with each configuration. Differences in T2 relaxation time measurements between dual-coil-array and single-coil-array acquisitions were compared with the standard repeatability of single-coil-array measurements using a Bland-Altman analysis.The mean g-factors for the dual-coil-array configuration were low for accelerations up to 6 in the right-left direction, and minimal cross-talk was observed between the two coil arrays. Image quality ratings of various joint tissues showed no difference in 89% (95% confidence interval: 85-93%) of rated image pairs, with only small differences ("slightly better" or "slightly worse") in image quality observed. The T2 relaxation time measurements between the dual-coil-array configuration and the single-coil configuration showed similar limits of agreement and concordance correlation coefficients (limits of agreement: -0.93 to 1.99 ms; CCC: 0.97 (95% confidence interval: 0.96-0.98)), to the repeatability of single-coil-array measurements (limits of agreement: -2.07 to 1.96 ms; CCC: 0.97 (95% confidence interval: 0.95-0.98)).A bilateral coil-array setup can image both knees simultaneously in similar scan times as conventional unilateral knee scans, with comparable image quality and quantitative accuracy. This has the potential to improve the value of MRI knee evaluations. Magn Reson Med 80:529-537, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

  View details for PubMedID 29250856

  View details for PubMedCentralID PMC5910219

• Quantitative imaging of bone-cartilage interactions in ACL-injured patients with PET-MRI. Osteoarthritis and cartilage Kogan, F. n., Fan, A. P., Monu, U. n., Iagaru, A. n., Hargreaves, B. A., Gold, G. E. 2018

  Abstract

  To investigate changes in bone metabolism by positron emission tomography (PET), as well as spatial relationships between bone metabolism and magnetic resonance imaging (MRI) quantitative markers of early cartilage degradation, in anterior cruciate ligament (ACL)-reconstructed knees.Both knees of 15 participants with unilateral reconstructed ACL tears and unaffected contralateral knees were scanned using a simultaneous 3.0T PET-MRI system following injection of 18F-sodium fluoride (18F-NaF). The maximum pixel standardized uptake value (SUVmax) in the subchondral bone and the average T2 relaxation time in cartilage were measured in each knee in eight knee compartments. We tested differences in SUVmax and cartilage T2 relaxation times between the ACL-injured knee and the contralateral control knee as well as spatial relationships between these bone and cartilage changes.Significantly increased subchondral bone 18F-NaF SUVmax and cartilage T2 times were observed in the ACL-reconstructed knees (median [inter-quartile-range (IQR)]: 5.0 [5.8], 36.8 [3.6] ms) compared to the contralateral knees (median [IQR]: 1.9 [1.4], 34.4 [3.8] ms). A spatial relationship between the two markers was also seen. Using the contralateral knee as a control, we observed a significant correlation of r = 0.59 between the difference in subchondral bone SUVmax (between injured and contralateral knees) and the adjacent cartilage T2 (between the two knees) [P < 0.001], with a slope of 0.49 ms/a.u. This correlation and slope were higher in deep layers (r = 0.73, slope = 0.60 ms/a.u.) of cartilage compared to superficial layers (r = 0.40, slope = 0.43 ms/a.u.).18F-NaF PET-MR imaging enables detection of increased subchondral bone metabolism in ACL-reconstructed knees and may serve as an important marker of early osteoarthritis (OA) progression. Spatial relationships observed between early OA changes across bone and cartilage support the need to study whole-joint disease mechanisms in OA.

  View details for PubMedID 29656143

• PET/MRI of Metabolic Activity in Osteoarthritis: A Feasibility Study JOURNAL OF MAGNETIC RESONANCE IMAGING Kogan, F., Fan, A. P., McWalter, E. J., Oei, E. H., Quon, A., Gold, G. E. 2017; 45 (6): 1736-1745

  Abstract

  To evaluate positron emission tomography / magnetic resonance imaging (PET/MRI) knee imaging to detect and characterize osseous metabolic abnormalities and correlate PET radiotracer uptake with osseous abnormalities and cartilage degeneration observed on MRI.Both knees of 22 subjects with knee pain or injury were scanned at one timepoint, without gadolinium, on a hybrid 3.0T PET-MRI system following injection of (18) F-fluoride or (18) F-fluorodeoxyglucose (FDG). A musculoskeletal radiologist identified volumes of interest (VOIs) around bone abnormalities on MR images and scored bone marrow lesions (BMLs) and osteophytes using a MOAKS scoring system. Cartilage appearance adjacent to bone abnormalities was graded with MRI-modified Outerbridge classifications. On PET standardized uptake values (SUV) maps, VOIs with SUV greater than 5 times the SUV in normal-appearing bone were identified as high-uptake VOI (VOIHigh ). Differences in (18) F-fluoride uptake between bone abnormalities, BML, and osteophyte grades and adjacent cartilage grades on MRI were identified using Mann-Whitney U-tests.SUVmax in all subchondral bone lesions (BML, osteophytes, sclerosis) was significantly higher than that of normal-appearing bone on MRI (P < 0.001 for all). Of the 172 high-uptake regions on (18) F-fluoride PET, 63 (37%) corresponded to normal-appearing subchondral bone on MRI. Furthermore, many small grade 1 osteophytes (40 of 82 [49%]), often described as the earliest signs of osteoarthritis (OA), did not show high uptake. Lastly, PET SUVmax in subchondral bone adjacent to grade 0 cartilage was significantly lower compared to that of grades 1-2 (P < 0.05) and grades 3-4 cartilage (P < 0.001).PET/MRI can simultaneously assess multiple early metabolic and morphologic markers of knee OA across multiple tissues in the joint. Our findings suggest that PET/MR may detect metabolic abnormalities in subchondral bone, which appear normal on MRI.2 J. Magn. Reson. Imaging 2016.

  View details for DOI 10.1002/jmri.25529

  View details for Web of Science ID 000401259900018

• A technique for in vivo mapping of myocardial creatine kinase metabolism. Nature medicine Haris, M., Singh, A., Cai, K., Kogan, F., McGarvey, J., Debrosse, C., Zsido, G. A., Witschey, W. R., Koomalsingh, K., Pilla, J. J., Chirinos, J. A., Ferrari, V. A., Gorman, J. H., Hariharan, H., Gorman, R. C., Reddy, R. 2014

  Abstract

  ATP derived from the conversion of phosphocreatine to creatine by creatine kinase provides an essential chemical energy source that governs myocardial contraction. Here, we demonstrate that the exchange of amine protons from creatine with protons in bulk water can be exploited to image creatine through chemical exchange saturation transfer (CrEST) in myocardial tissue. We show that CrEST provides about two orders of magnitude higher sensitivity compared to (1)H magnetic resonance spectroscopy. Results of CrEST studies from ex vivo myocardial tissue strongly correlate with results from (1)H and (31)P magnetic resonance spectroscopy and biochemical analysis. We demonstrate the feasibility of CrEST measurement in healthy and infarcted myocardium in animal models in vivo on a 3-T clinical scanner. As proof of principle, we show the conversion of phosphocreatine to creatine by spatiotemporal mapping of creatine changes in the exercised human calf muscle. We also discuss the potential utility of CrEST in studying myocardial disorders.

  View details for DOI 10.1038/nm.3436

  View details for PubMedID 24412924

• Method for high-resolution imaging of creatine in vivo using chemical exchange saturation transfer. Magnetic resonance in medicine Kogan, F., Haris, M., Singh, A., Cai, K., Debrosse, C., Nanga, R. P., Hariharan, H., Reddy, R. 2014; 71 (1): 164-172

  Abstract

  To develop a chemical exchange saturation transfer (CEST)-based technique to measure free creatine (Cr) and to validate the technique by measuring the distribution of Cr in muscle with high spatial resolution before and after exercise.Phantom studies were performed to determine contributions from other Cr kinase metabolites to the CEST effect from Cr (CrCEST). CEST, T2 , magnetization transfer ratio and (31) P magnetic resonance spectroscopy acquisitions of the lower leg were performed before and after plantar flexion exercise on a 7T whole-body magnetic resonance scanner on healthy volunteers.Phantom studies demonstrated that while Cr exhibited significant CEST effect there were no appreciable contributions from other metabolites. In healthy human subjects, following mild plantar flexion exercise, increases in the CEST effect from Cr were observed, which recovered exponentially back to baseline. This technique exhibited good spatial resolution and was able to differentiate differences in muscle utilization among subjects. The CEST effect from Cr results were compared with (31) P magnetic resonance spectroscopy results showing good agreement in the Cr and phosphocreatine recovery kinetics.Demonstrated a CEST-based technique to measure free Cr changes in in vivo muscle. The CEST effect from Cr imaging can spatially map changes in Cr concentration in muscle following mild exercise. This may serve as a tool for the diagnosis and treatment of various disorders affecting muscle. Magn Reson Med 71:164-172, 2014. © 2013 Wiley Periodicals, Inc.

  View details for DOI 10.1002/mrm.24641

  View details for PubMedID 23412909

• Magnetic resonance imaging of glutamate NATURE MEDICINE Cai, K., Haris, M., Singh, A., Kogan, F., Greenberg, J. H., Hariharan, H., Detre, J. A., Reddy, R. 2012; 18 (2): 302-306

  Abstract

  Glutamate, a major neurotransmitter in the brain, shows a pH- and concentration-dependent chemical exchange saturation transfer effect (GluCEST) between its amine group and bulk water, with potential for in vivo imaging by nuclear magnetic resonance. GluCEST asymmetry is observed ∼3 p.p.m. downfield from bulk water. Middle cerebral artery occlusion in the rat brain resulted in an ∼100% elevation of GluCEST in the ipsilateral side compared with the contralateral side, predominantly owing to pH changes. In a rat brain tumor model with blood-brain barrier disruption, intravenous glutamate injection resulted in a clear elevation of GluCEST and a similar increase in the proton magnetic resonance spectroscopy signal of glutamate. GluCEST maps from healthy human brain were also obtained. These results demonstrate the feasibility of using GluCEST for mapping relative changes in glutamate concentration, as well as pH, in vivo. Contributions from other brain metabolites to the GluCEST effect are also discussed.

  View details for Web of Science ID 000300140300047

  View details for PubMedID 22270722

• PET-MRI: the promise of multi-tissue imaging of early disease mechanisms in osteoarthritis. Osteoarthritis and cartilage Kogan, F., Watkins, L. E., Goyal, A. 2024

  View details for DOI 10.1016/j.joca.2024.10.011

  View details for PubMedID 39489372

• Improving Accuracy and Reproducibility of Cartilage T2 Mapping in the OAI Dataset Through Extended Phase Graph Modeling. Journal of magnetic resonance imaging : JMRI Barbieri, M., Gatti, A. A., Kogan, F. 2024

  Abstract

  The Osteoarthritis Initiative (OAI) collected extensive imaging data, including Multi-Echo Spin-Echo (MESE) sequences for measuring knee cartilage T2 relaxation times. Mono-exponential models are used in the OAI for T2 fitting, which neglects stimulated echoes and B1 inhomogeneities. Extended Phase Graph (EPG) modeling addresses these limitations but has not been applied to the OAI dataset.To assess how different fitting methods, including EPG-based and exponential-based approaches, affect the accuracy and reproducibility of cartilage T2 in the OAI dataset.Retrospective.From OAI dataset, 50 subjects, stratified by osteoarthritis (OA) severity using Kellgren-Lawrence grades (KLG), and 50 subjects without OA diagnosis during OAI duration were selected (each group: 25 females, mean ages ~61 years).3-T, two-dimensional (2D) MESE sequence.Femoral and tibial cartilages were segmented from DESS images, subdivided into seven sub-regions, and co-registered to MESE. T2 maps were obtained using three EPG-based methods (nonlinear least squares, dictionary matching, and deep learning) and three mono-exponential approaches (linear least squares, nonlinear least squares, and noise-corrected exponential). Average T2 values within sub-regions were obtained. Pair-wise agreement among fitting methods was evaluated using the stratified subjects, while reproducibility using healthy subjects. Each method's T2 accuracy and repeatability varying signal-to-noise ratio (SNR) were assessed with simulations.Bland-Altman analysis, Lin's concordance coefficient, and coefficient of variation assessed agreement, repeatability, and reproducibility. Statistical significance was set at P-value <0.05.EPG-based methods demonstrated superior T2 accuracy (mean absolute error below 0.5 msec at SNR > 100) compared to mono-exponential methods (error > 7 msec). EPG-based approaches had better reproducibility, with limits of agreement 1.5-5 msec narrower than exponential-based methods. T2 values from EPG methods were systematically 10-17 msec lower than those from mono-exponential fitting.EPG modeling improved agreement and reproducibility of cartilage T2 mapping in subjects from the OAI dataset.3 TECHNICAL EFFICACY: Stage 1.

  View details for DOI 10.1002/jmri.29646

  View details for PubMedID 39467097

• ShapeMed-Knee: A Dataset and Neural Shape Model Benchmark for Modeling 3D Femurs. medRxiv : the preprint server for health sciences Gatti, A. A., Blankemeier, L., Van Veen, D., Hargreaves, B., Delp, S. L., Gold, G. E., Kogan, F., Chaudhari, A. S. 2024

  Abstract

  Analyzing anatomic shapes of tissues and organs is pivotal for accurate disease diagnostics and clinical decision-making. One prominent disease that depends on anatomic shape analysis is osteoarthritis, which affects 30 million Americans. To advance osteoarthritis diagnostics and prognostics, we introduce ShapeMed-Knee, a 3D shape dataset with 9,376 high-resolution, medical-imaging-based 3D shapes of both femur bone and cartilage. Besides data, ShapeMed-Knee includes two benchmarks for assessing reconstruction accuracy and five clinical prediction tasks that assess the utility of learned shape representations. Leveraging ShapeMed-Knee, we develop and evaluate a novel hybrid explicit-implicit neural shape model which achieves up to 40% better reconstruction accuracy than a statistical shape model and implicit neural shape model. Our hybrid models achieve state-of-the-art performance for preserving cartilage biomarkers; they're also the first models to successfully predict localized structural features of osteoarthritis, outperforming shape models and convolutional neural networks applied to raw magnetic resonance images and segmentations. The ShapeMed-Knee dataset provides medical evaluations to reconstruct multiple anatomic surfaces and embed meaningful disease-specific information. ShapeMed-Knee reduces barriers to applying 3D modeling in medicine, and our benchmarks highlight that advancements in 3D modeling can enhance the diagnosis and risk stratification for complex diseases. The dataset, code, and benchmarks will be made freely accessible.

  View details for DOI 10.1101/2024.05.06.24306965

  View details for PubMedID 38766040

• A deep learning approach for fast muscle water T2 mapping with subject specific fat T2 calibration from multi-spin-echo acquisitions. Scientific reports Barbieri, M., Hooijmans, M. T., Moulin, K., Cork, T. E., Ennis, D. B., Gold, G. E., Kogan, F., Mazzoli, V. 2024; 14 (1): 8253

  Abstract

  This work presents a deep learning approach for rapid and accurate muscle water T2 with subject-specific fat T2 calibration using multi-spin-echo acquisitions. This method addresses the computational limitations of conventional bi-component Extended Phase Graph fitting methods (nonlinear-least-squares and dictionary-based) by leveraging fully connected neural networks for fast processing with minimal computational resources. We validated the approach through in vivo experiments using two different MRI vendors. The results showed strong agreement of our deep learning approach with reference methods, summarized by Lin's concordance correlation coefficients ranging from 0.89 to 0.97. Further, the deep learning method achieved a significant computational time improvement, processing data 116 and 33 times faster than the nonlinear least squares and dictionary methods, respectively. In conclusion, the proposed approach demonstrated significant time and resource efficiency improvements over conventional methods while maintaining similar accuracy. This methodology makes the processing of water T2 data faster and easier for the user and will facilitate the utilization of the use of a quantitative water T2 map of muscle in clinical and research studies.

  View details for DOI 10.1038/s41598-024-58812-2

  View details for PubMedID 38589478

  View details for PubMedCentralID 6398566

• Correction to: Multimodal positron emission tomography (PET) imaging in non-oncologic musculoskeletal radiology. Skeletal radiology Kogan, F., Yoon, D., Teeter, M. G., Chaudhari, A. J., Hales, L., Barbieri, M., Gold, G. E., Vainberg, Y., Goyal, A., Watkins, L. 2024

  View details for DOI 10.1007/s00256-024-04667-7

  View details for PubMedID 38557699

• Multimodal positron emission tomography (PET) imaging in non-oncologic musculoskeletal radiology. Skeletal radiology Kogan, F., Yoon, D., Teeter, M. G., Chaudhari, A. J., Hales, L., Barbieri, M., Gold, G. E., Vainberg, Y., Goyal, A., Watkins, L. 2024

  Abstract

  Musculoskeletal (MSK) disorders are associated with large impacts on patient's pain and quality of life. Conventional morphological imaging of tissue structure is limited in its ability to detect pain generators, early MSK disease, and rapidly assess treatment efficacy. Positron emission tomography (PET), which offers unique capabilities to evaluate molecular and metabolic processes, can provide novel information about early pathophysiologic changes that occur before structural or even microstructural changes can be detected. This sensitivity not only makes it a powerful tool for detection and characterization of disease, but also a tool able to rapidly assess the efficacy of therapies. These benefits have garnered more attention to PET imaging of MSK disorders in recent years. In this narrative review, we discuss several applications of multimodal PET imaging in non-oncologic MSK diseases including arthritis, osteoporosis, and sources of pain and inflammation. We also describe technical considerations and recent advancements in technology and radiotracers as well as areas of emerging interest for future applications of multimodal PET imaging of MSK conditions. Overall, we present evidence that the incorporation of PET through multimodal imaging offers an exciting addition to the field of MSK radiology and will likely prove valuable in the transition to an era of precision medicine.

  View details for DOI 10.1007/s00256-024-04640-4

  View details for PubMedID 38492029

  View details for PubMedCentralID 6899769

• Advanced Magnetic Resonance Imaging and Molecular Imaging of the Painful Knee. Seminars in musculoskeletal radiology Mostert, J. M., Dur, N. B., Li, X., Ellermann, J. M., Hemke, R., Hales, L., Mazzoli, V., Kogan, F., Griffith, J. F., Oei, E. H., van der Heijden, R. A. 2023; 27 (6): 618-631

  Abstract

  Chronic knee pain is a common condition. Causes of knee pain include trauma, inflammation, and degeneration, but in many patients the pathophysiology remains unknown. Recent developments in advanced magnetic resonance imaging (MRI) techniques and molecular imaging facilitate more in-depth research focused on the pathophysiology of chronic musculoskeletal pain and more specifically inflammation. The forthcoming new insights can help develop better targeted treatment, and some imaging techniques may even serve as imaging biomarkers for predicting and assessing treatment response in the future. This review highlights the latest developments in perfusion MRI, diffusion MRI, and molecular imaging with positron emission tomography/MRI and their application in the painful knee. The primary focus is synovial inflammation, also known as synovitis. Bone perfusion and bone metabolism are also addressed.

  View details for DOI 10.1055/s-0043-1775741

  View details for PubMedID 37935208

• Advanced MRI Approaches for Evaluating Common Lower Extremity Injuries in Basketball Players: Current and Emerging Techniques. Journal of magnetic resonance imaging : JMRI Rubin, E. B., Schmidt, A. M., Koff, M. F., Kogan, F., Gao, K., Majumdar, S., Potter, H., Gold, G. E. 2023

  Abstract

  Magnetic resonance imaging (MRI) can provide accurate and non-invasive diagnoses of lower extremity injuries in athletes. Sport-related injuries commonly occur in and around the knee and can affect the articular cartilage, patellar tendon, hamstring muscles, and bone. Sports medicine physicians utilize MRI to evaluate and diagnose injury, track recovery, estimate return to sport timelines, and assess the risk of recurrent injury. This article reviews the current literature and describes novel developments of quantitative MRI tools that can further advance our understanding of sports injury diagnosis, prevention, and treatment while minimizing injury risk and rehabilitation time. Innovative approaches for enhancing the early diagnosis and treatment of musculoskeletal injuries in basketball players span a spectrum of techniques. These encompass the utilization of T2 , T1ρ , and T2 * quantitative MRI, along with dGEMRIC and Na-MRI to assess articular cartilage injuries, 3D-Ultrashort echo time MRI for patellar tendon injuries, diffusion tensor imaging for acute myotendinous injuries, and sagittal short tau inversion recovery and axial long-axis T1 -weighted, and 3D Cube sequences for bone stress imaging. Future studies should further refine and validate these MR-based quantitative techniques while exploring the lifelong cumulative impact of basketball on players' knees. LEVEL OF EVIDENCE: 5 TECHNICAL EFFICACY: Stage 2.

  View details for DOI 10.1002/jmri.29019

  View details for PubMedID 37854004

• [Formula: see text] Field inhomogeneity correction for qDESS [Formula: see text] mapping: application to rapid bilateral knee imaging. Magma (New York, N.Y.) Barbieri, M., Watkins, L. E., Mazzoli, V., Desai, A. D., Rubin, E., Schmidt, A., Gold, G. E., Hargreaves, B. A., Chaudhari, A. S., Kogan, F. 2023

  Abstract

  [Formula: see text] mapping is a powerful tool for studying osteoarthritis (OA) changes and bilateral imaging may be useful in investigating the role of between-knee asymmetry in OA onset and progression. The quantitative double-echo in steady-state (qDESS) can provide fast simultaneous bilateral knee [Formula: see text] and high-resolution morphometry for cartilage and meniscus. The qDESS uses an analytical signal model to compute [Formula: see text] relaxometry maps, which require knowledge of the flip angle (FA). In the presence of [Formula: see text] inhomogeneities, inconsistencies between the nominal and actual FA can affect the accuracy of [Formula: see text] measurements. We propose a pixel-wise [Formula: see text] correction method for qDESS [Formula: see text] mapping exploiting an auxiliary [Formula: see text] map to compute the actual FA used in the model.The technique was validated in a phantom and in vivo with simultaneous bilateral knee imaging. [Formula: see text] measurements of femoral cartilage (FC) of both knees of six healthy participants were repeated longitudinally to investigate the association between [Formula: see text] variation and [Formula: see text].The results showed that applying the [Formula: see text] correction mitigated [Formula: see text] variations that were driven by [Formula: see text] inhomogeneities. Specifically, [Formula: see text] left-right symmetry increased following the [Formula: see text] correction ([Formula: see text] = 0.74 > [Formula: see text] = 0.69). Without the [Formula: see text] correction, [Formula: see text] values showed a linear dependence with [Formula: see text]. The linear coefficient decreased using the [Formula: see text] correction (from 24.3 ± 1.6 ms to 4.1 ± 1.8) and the correlation was not statistically significant after the application of the Bonferroni correction (p value > 0.01).The study showed that [Formula: see text] correction could mitigate variations driven by the sensitivity of the qDESS [Formula: see text] mapping method to [Formula: see text], therefore, increasing the sensitivity to detect real biological changes. The proposed method may improve the robustness of bilateral qDESS [Formula: see text] mapping, allowing for an accurate and more efficient evaluation of OA pathways and pathophysiology through longitudinal and cross-sectional studies.

  View details for DOI 10.1007/s10334-023-01094-y

  View details for PubMedID 37142852

  View details for PubMedCentralID 2268124

• Design and Rationale of RE-ENERGIZE FONTAN: RandomizEd Exercise iNtERvention desiGned to maximIZE fitness in FONTAN patients. American heart journal Tierney, E. S., Palaniappan, L., Leonard, M., Long, J., Myers, J., Dávila, T., Lui, M. C., Kogan, F., Olson, I., Punn, R., Desai, M., Schneider, L. M., Wang, C. H., Cooke, J. P., Bernstein, D. 2023

  Abstract

  In this manuscript, we describe the design and rationale of a randomized controlled trial in pediatric Fontan patients to test the hypothesis that a live-video-supervised exercise (aerobic+resistance) intervention will improve cardiac and physical capacity; muscle mass, strength, and function; and endothelial function. Survival of children with single ventricles beyond the neonatal period has increased dramatically with the staged Fontan palliation. Yet, long-term morbidity remains high. By age 40, 50% of Fontan patients will have died or undergone heart transplantation. Factors that contribute to onset and progression of heart failure in Fontan patients remain incompletely understood. However, it is established that Fontan patients have poor exercise capacity which is associated with a greater risk of morbidity and mortality. Furthermore, decreased muscle mass, abnormal muscle function, and endothelial dysfunction in this patient population is known to contribute to disease progression. In adult patients with two ventricles and heart failure, reduced exercise capacity, muscle mass, and muscle strength are powerful predictors of poor outcomes, and exercise interventions can not only improve exercise capacity and muscle mass, but also reverse endothelial dysfunction. Despite these known benefits of exercise, pediatric Fontan patients do not exercise routinely due to their chronic condition, perceived restrictions to exercise, and parental overprotection. Limited exercise interventions in children with congenital heart disease have demonstrated that exercise is safe and effective; however, these studies have been conducted in small, heterogeneous groups, and most had few Fontan patients. Critically, adherence is a major limitation in pediatric exercise interventions delivered on-site, with adherence rates as low as 10%, due to distance from site, transportation difficulties, and missed school or workdays. To overcome these challenges, we utilize live-video conferencing to deliver the supervised exercise sessions. Our multidisciplinary team of experts will assess the effectiveness of a live-video-supervised exercise intervention, rigorously designed to maximize adherence, and improve key and novel measures of health in pediatric Fontan patients associated with poor long-term outcomes. Our ultimate goal is the translation of this model to clinical application as an "exercise prescription" to intervene early in pediatric Fontan patients and decrease long-term morbidity and mortality.

  View details for DOI 10.1016/j.ahj.2023.02.006

  View details for PubMedID 36796574

• Imaging of joint response to exercise with MRI and PET. Skeletal radiology Watkins, L. E., Goyal, A., Gatti, A. A., Kogan, F. 2023

  Abstract

  Imaging of the joint in response to loading stress may provide additional measures of joint structure and function beyond conventional, static imaging studies. Exercise such as running, stair climbing, and squatting allows evaluation of the joint response to larger loading forces than during weight bearing. Quantitative MRI (qMRI) may assess properties of cartilage and meniscus hydration and organization in vivo that have been investigated to assess the functional response of these tissues to physiological stress. [18F]sodium fluoride ([18F]NaF) interrogates areas of newly mineralizing bone and provides an opportunity to study bone physiology, including perfusion and mineralization rate, as a measure of joint loading stress. In this review article, methods utilizing quantitative MRI, PET, and hybrid PET-MRI systems for assessment of the joint response to loading from exercise in vivo are examined. Both methodology and results of various studies performed are outlined and discussed. Lastly, the technical considerations, challenges, and future opportunities for these approaches are addressed.

  View details for DOI 10.1007/s00256-022-04271-7

  View details for PubMedID 36646851

• PET Imaging in Osteoarthritis. PET clinics Jarraya, M., Roemer, F. W., Bäuerle, T., Kogan, F., Guermazi, A. 2023; 18 (1): 21-29

  Abstract

  Osteoarthritis is a common cause of pain and morbidity resulting in heavy economic burden and large societal costs. Although cross-sectional imaging and in particular MR imaging have largely contributed to a better understanding of the complexity of this complex disease, especially in large joints such as the hip and knee joints, metabolic information of the subchondral bone and periarticular synovial environment has been consistently suggested to provide valuable supplemental information to morphologic and compositional MR imaging. The aim of this narrative review is to provide an overview of the role of the hybrid PET imaging in osteoarthritis with particular focus on PET/MR imaging.

  View details for DOI 10.1016/j.cpet.2022.09.002

  View details for PubMedID 36442963

• Effects of dynamic [18F]NaF PET scan duration on kinetic uptake parameters in the knee. Frontiers in nuclear medicine (Lausanne, Switzerland) Watkins, L. E., Haddock, B., Goyal, A., Kogan, F. 2023; 3: 1194961

  Abstract

  Introduction: Accurately estimating bone perfusion and metabolism using [18F]NaF kinetics from shorter scan times could help address concerns related to patient comfort, motion, and throughput for PET scans. We examined the impact of changing the PET scan duration on the accuracy of [18F]NaF kinetic parameters in the knee.Methods: Both knees of twenty participants with and without osteoarthritis were scanned using a hybrid PET-MRI system (53±13 years, BMI 25.9±4.2 kg/m2, 13 female). Seventeen participants were scanned for 54±2 min, and an additional three participants were scanned for 75 min. Patlak K i and Hawkins kinetic parameters (K i, K 1, extraction fraction) were assessed using 50- or 75-minutes of scan data as well as for scan durations that were retrospectively shortened. The error of the kinetic uptake parameters was calculated in bone regions throughout the knee.Results: The mean error of Patlak K i, Hawkins K i, K 1, and extraction fraction was less than 10% for scan durations exceeding 30 min and decreased with increasing scan duration.Conclusions: The length of dynamic data acquisition can be reduced to as short as 30 min while retaining accuracy within the limits of reproducibility of Hawkins kinetic uptake parameters.

  View details for DOI 10.3389/fnume.2023.1194961

  View details for PubMedID 39355034

• Latest advancements in imaging techniques in OA. Therapeutic advances in musculoskeletal disease Hayashi, D., Roemer, F. W., Link, T., Li, X., Kogan, F., Segal, N. A., Omoumi, P., Guermazi, A. 2022; 14: 1759720X221146621

  Abstract

  The osteoarthritis (OA) research community has been advocating a shift from radiography-based screening criteria and outcome measures in OA clinical trials to a magnetic resonance imaging (MRI)-based definition of eligibility and endpoint. For conventional morphological MRI, various semiquantitative evaluation tools are available. We have lately witnessed a remarkable technological advance in MRI techniques, including compositional/physiologic imaging and automated quantitative analyses of articular and periarticular structures. More recently, additional technologies were introduced, including positron emission tomography (PET)-MRI, weight-bearing computed tomography (CT), photon-counting spectral CT, shear wave elastography, contrast-enhanced ultrasound, multiscale X-ray phase contrast imaging, and spectroscopic photoacoustic imaging of cartilage. On top of these, we now live in an era in which artificial intelligence is increasingly utilized in medicine. Osteoarthritis imaging is no exception. Successful implementation of artificial intelligence (AI) will hopefully improve the workflow of radiologists, as well as the level of precision and reproducibility in the interpretation of images.

  View details for DOI 10.1177/1759720X221146621

  View details for PubMedID 36601087

  View details for PubMedCentralID PMC9806406

• Editorial for "Local Patterns in Two-Year T1rho and T2 Changes in Hip Cartilage Are Related to Sex and Functional Data: A Prospective Evaluation on Hip Osteoarthritis Participants". Journal of magnetic resonance imaging : JMRI MacKay, J., Watkins, L., Kogan, F. 2022

  View details for DOI 10.1002/jmri.28446

  View details for PubMedID 36286012

• A method for measuring B0 field inhomogeneity using quantitative double-echo in steady-state. Magnetic resonance in medicine Barbieri, M., Chaudhari, A. S., Moran, C. J., Gold, G. E., Hargreaves, B. A., Kogan, F. 2022

  Abstract

  To develop and validate a method for B 0 $$ {B}_0 $$ mapping for knee imaging using the quantitative Double-Echo in Steady-State (qDESS) exploiting the phase difference ( Δ θ $$ \Delta \theta $$ ) between the two echoes acquired. Contrary to a two-gradient-echo (2-GRE) method, Δ θ $$ \Delta \theta $$ depends only on the first echo time.Bloch simulations were applied to investigate robustness to noise of the proposed methodology and all imaging studies were validated with phantoms and in vivo simultaneous bilateral knee acquisitions. Two phantoms and five healthy subjects were scanned using qDESS, water saturation shift referencing (WASSR), and multi-GRE sequences. Δ B 0 $$ \Delta {B}_0 $$ maps were calculated with the qDESS and the 2-GRE methods and compared against those obtained with WASSR. The comparison was quantitatively assessed exploiting pixel-wise difference maps, Bland-Altman (BA) analysis, and Lin's concordance coefficient ( ρ c $$ {\rho}_c $$ ). For in vivo subjects, the comparison was assessed in cartilage using average values in six subregions.The proposed method for measuring Δ B 0 $$ \Delta {B}_0 $$ inhomogeneities from a qDESS acquisition provided Δ B 0 $$ \Delta {B}_0 $$ maps that were in good agreement with those obtained using WASSR. Δ B 0 $$ \Delta {B}_0 $$ ρ c $$ {\rho}_c $$ values were ≥ $$ \ge $$ 0.98 and 0.90 in phantoms and in vivo, respectively. The agreement between qDESS and WASSR was comparable to that of a 2-GRE method.The proposed method may allow B0 correction for qDESS T 2 $$ {T}_2 $$ mapping using an inherently co-registered Δ B 0 $$ \Delta {B}_0 $$ map without requiring an additional B0 measurement sequence. More generally, the method may help shorten knee imaging protocols that require an auxiliary Δ B 0 $$ \Delta {B}_0 $$ map by exploiting a qDESS acquisition that also provides T 2 $$ {T}_2 $$ measurements and high-quality morphological imaging.

  View details for DOI 10.1002/mrm.29465

  View details for PubMedID 36161727

• 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

  Abstract

  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

• 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

  Abstract

  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

• Imaging of Synovial Inflammation in Osteoarthritis, From the AJR Special Series on Inflammation. AJR. American journal of roentgenology Thoenen, J., MacKay, J. W., Sandford, H. J., Gold, G. E., Kogan, F. 2021

  Abstract

  Synovitis, inflammation of the synovial membrane, is a common manifestation in osteoarthritis (OA) and is recognized to play a role in the complex pathophysiology of OA. Increased recognition of the importance of synovitis in the OA disease process and potential as a target for treatment has increased the need for non-invasive detection and characterization of synovitis using medical imaging. Numerous imaging methods can assess synovitis involvement in OA with varying sensitivity and specificity as well as complexity. This article reviews the role of contrast-enhanced MRI, conventional MRI, novel unenhanced MRI, gray-scale ultrasound (US), and power Doppler US in the assessment of synovitis in patients with OA. The role of imaging in disease evaluation as well as challenges in conventional imaging methods are discussed. We also provide an overview into the potential utility of emerging techniques for imaging of early inflammation and molecular inflammatory markers of synovitis, including quantitative MRI, superb microvascular imaging, and PET. The potential development of therapeutic treatments targeting inflammatory features, particularly in early OA, would greatly increase the importance of these imaging methods for clinical decision making and evaluation of therapeutic efficacy.

  View details for DOI 10.2214/AJR.21.26170

  View details for PubMedID 34286595

• Characterization of Structural Bone Properties through Portable Single-Sided NMR Devices: State of the Art and Future Perspectives. International journal of molecular sciences Barbieri, M., Fantazzini, P., Testa, C., Bortolotti, V., Baruffaldi, F., Kogan, F., Brizi, L. 2021; 22 (14)

  Abstract

  Nuclear Magnetic Resonance (NMR) is a well-suited methodology to study bone composition and structural properties. This is because the NMR parameters, such as the T2 relaxation time, are sensitive to the chemical and physical environment of the 1H nuclei. Although magnetic resonance imaging (MRI) allows bone structure assessment in vivo, its cost limits the suitability of conventional MRI for routine bone screening. With difficulty accessing clinically suitable exams, the diagnosis of bone diseases, such as osteoporosis, and the associated fracture risk estimation is based on the assessment of bone mineral density (BMD), obtained by the dual-energy X-ray absorptiometry (DXA). However, integrating the information about the structure of the bone with the bone mineral density has been shown to improve fracture risk estimation related to osteoporosis. Portable NMR, based on low-field single-sided NMR devices, is a promising and appealing approach to assess NMR properties of biological tissues with the aim of medical applications. Since these scanners detect the signal from a sensitive volume external to the magnet, they can be used to perform NMR measurement without the need to fit a sample inside a bore of a magnet, allowing, in principle, in vivo application. Techniques based on NMR single-sided devices have the potential to provide a high impact on the clinical routine because of low purchasing and running costs and low maintenance of such scanners. In this review, the development of new methodologies to investigate structural properties of trabecular bone exploiting single-sided NMR devices is reviewed, and current limitations and future perspectives are discussed.

  View details for DOI 10.3390/ijms22147318

  View details for PubMedID 34298936

• 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

  Abstract

  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

  Abstract

  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

  Abstract

  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

  Abstract

  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

• Standardized multi-vendor compositional MRI of knee cartilage: a key step towards clinical translation? Osteoarthritis and cartilage MacKay, J. W., Roemer, F. W., Kogan, F. 2020

  View details for DOI 10.1016/j.joca.2020.08.007

  View details for PubMedID 32882389

• 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

  Abstract

  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

• Identifying Musculoskeletal Pain Generators Using Clinical PET. Seminars in musculoskeletal radiology Yoon, D. n., Kogan, F. n., Gold, G. E., Biswal, S. n. 2020; 24 (4): 441–50

  Abstract

  Identifying the source of a person's pain is a significant clinical challenge because the physical sensation of pain is believed to be subjective and difficult to quantify. The experience of pain is not only modulated by the individual's threshold to painful stimuli but also a product of the person's affective contributions, such as fear, anxiety, and previous experiences. Perhaps then to quantify pain is to examine the degree of nociception and pro-nociceptive inflammation, that is, the extent of cellular, chemical, and molecular changes that occur in pain-generating processes. Measuring changes in the local density of receptors, ion channels, mediators, and inflammatory/immune cells that are involved in the painful phenotype using targeted, highly sensitive, and specific positron emission tomography (PET) radiotracers is therefore a promising approach toward objectively identifying peripheral pain generators. Although several preclinical radiotracer candidates are being developed, a growing number of ongoing clinical PET imaging approaches can measure the degree of target concentration and thus serve as a readout for sites of pain generation. Further, when PET is combined with the spatial and contrast resolution afforded by magnetic resonance imaging, nuclear medicine physicians and radiologists can potentially identify pain drivers with greater accuracy and confidence. Clinical PET imaging approaches with fluorine-18 fluorodeoxyglucose, fluorine-18 sodium fluoride, and sigma-1 receptor PET radioligand and translocator protein radioligands to isolate the source of pain are described here.

  View details for DOI 10.1055/s-0040-1713607

  View details for PubMedID 32992371

• Multiparametric MRI Characterization of Knee Articular Cartilage and Subchondral Bone Shape in Collegiate Basketball Players. Journal of orthopaedic research : official publication of the Orthopaedic Research Society Gao, K. T., Pedoia, V. n., Young, K. A., Kogan, F. n., Koff, M. F., Gold, G. E., Potter, H. G., Majumdar, S. n. 2020

  Abstract

  Magnetic resonance imaging (MRI) is commonly used to evaluate the morphology of the knee in athletes with high knee impact; however, complex repeated loading of the joint can lead to biochemical and structural degeneration that occur prior to visible morphological changes. In this study, we utilized multiparametric quantitative MRI to compare morphology and composition of articular cartilage and subchondral bone shape between young athletes with high knee impact (basketball players; n = 40) and non-knee impact (swimmers; n = 25). We implemented voxel-based relaxometry to register all cases to a single reference space and performed localized compositional analysis of T1ρ - and T2 -relaxation times on a voxel-by-voxel basis. Additionally, statistical shape modeling was employed to extract differences in subchondral bone shape between the two groups. Evaluation of cartilage composition demonstrated significant prolongation of relaxation times in the medial femoral and tibial compartments and in the posterolateral femur of basketball players in comparison to relaxation times in the same cartilage compartments of swimmers. Compositional analysis also showed depth-dependent differences with prolongation of the superficial layer in basketball players. For subchondral bone shape, 3 total modes were found to be significantly different between groups and related to the relative sizes of the tibial plateaus, intercondylar eminences, and the curvature and concavity of the patellar lateral facet. In summary, this study identified several characteristics associated with high knee impact which may expand our understanding of local degenerative patterns in this population. This article is protected by copyright. All rights reserved.

  View details for DOI 10.1002/jor.24851

  View details for PubMedID 32910520

• The prevalence of femoroacetabular impingement anatomy in Division 1 aquatic athletes who tread water Journal of Hip Preservation Surgery Langner, J. L., Black, M. S., MacKay, J. W., Hall, K. E., Safran, M. R., Kogan, F., Gold, G. E. 2020; 0: 1-9

  Abstract

  Femoroacetabular impingement (FAI) is a disorder that causes hip pain and disability in young patients, particularly athletes. Increased stress on the hip during development has been associated with increased risk of cam morphology. The specific forces involved are unclear, but may be due to continued rotational motion, like the eggbeater kick. The goal of this prospective cohort study was to use magnetic resonance imaging (MRI) to identify the prevalence of FAI anatomy in athletes who tread water and compare it to the literature on other sports. With university IRB approval, 20 Division 1 water polo players and synchronized swimmers (15 female, 5 male), ages 18-23 years (mean age 20.7 ± 1.4), completed the 33-item International Hip Outcome Tool and underwent non-contrast MRI scans of both hips using a 3 Tesla scanner. Recruitment was based on sport, with both symptomatic and asymptomatic individuals included. Cam and pincer morphology were identified. The Wilcoxon Signed-Rank/Rank Sum tests were used to assess outcomes. Seventy per cent (14/20) of subjects reported pain in their hips yet only 15% (3/20) sought clinical evaluation. Cam morphology was present in 67.5% (27/40) of hips, while 22.5% (9/40) demonstrated pincer morphology. The prevalence of cam morphology in water polo players and synchronized swimmers is greater than that reported for the general population and at a similar level as some other sports. From a clinical perspective, acknowledgment of the high prevalence of cam morphology in water polo players and synchronized swimmers should be considered when these athletes present with hip pain.

  View details for DOI 10.1093/jhps/hnaa009

  View details for PubMedCentralID PMC7605769

• Rapid Knee MRI Acquisition and Analysis Techniques for Imaging Osteoarthritis. Journal of magnetic resonance imaging : JMRI Chaudhari, A. S., Kogan, F., Pedoia, V., Majumdar, S., Gold, G. E., Hargreaves, B. A. 2019

  Abstract

  Osteoarthritis (OA) of the knee is a major source of disability that has no known treatment or cure. Morphological and compositional MRI is commonly used for assessing the bone and soft tissues in the knee to enhance the understanding of OA pathophysiology. However, it is challenging to extend these imaging methods and their subsequent analysis techniques to study large population cohorts due to slow and inefficient imaging acquisition and postprocessing tools. This can create a bottleneck in assessing early OA changes and evaluating the responses of novel therapeutics. The purpose of this review article is to highlight recent developments in tools for enhancing the efficiency of knee MRI methods useful to study OA. Advances in efficient MRI data acquisition and reconstruction tools for morphological and compositional imaging, efficient automated image analysis tools, and hardware improvements to further drive efficient imaging are discussed in this review. For each topic, we discuss the current challenges as well as potential future opportunities to alleviate these challenges. LEVEL OF EVIDENCE: 5 TECHNICAL EFFICACY STAGE: 3.

  View details for DOI 10.1002/jmri.26991

  View details for PubMedID 31755191

• Combined 5-minute double-echo in steady-state with separated echoes and 2-minute proton-density-weighted 2D FSE sequence for comprehensive whole-joint knee MRI assessment JOURNAL OF MAGNETIC RESONANCE IMAGING Chaudhari, A. S., Stevens, K. J., Sveinsson, B., Wood, J. P., Beaulieu, C. F., Oei, E. G., Rosenberg, J. K., Kogan, F., Alley, M. T., Gold, G. E., Hargreaves, B. A. 2019; 49 (7): E183–E194

  View details for DOI 10.1002/jmri.26582

  View details for Web of Science ID 000474612300018

• Kinetic [F-18]-Fluoride of the Knee in Normal Volunteers CLINICAL NUCLEAR MEDICINE Haddock, B., Fan, A. P., Jorgensen, N. R., Suetta, C., Gold, G., Kogan, F. 2019; 44 (5): 377–85

  View details for DOI 10.1097/RLU.0000000000002533

  View details for Web of Science ID 000465173700022

• Applications of PET-Computed Tomography-Magnetic Resonance in the Management of Benign Musculoskeletal Disorders. PET clinics Yoder, J. S., Kogan, F., Gold, G. E. 2019; 14 (1): 1–15

  Abstract

  Although computed tomography (CT) and MR imaging alone have been used extensively to evaluate various musculoskeletal disorders, hybrid imaging modalities of PET-CT and PET-MR imaging were recently developed, combining the advantages of each method: molecular information from PET and anatomical information from CT or MR imaging. Furthermore, different radiotracers can be used in PET to uncover different disease mechanisms. In this article, potential applications of PET-CT and PET-MR imaging for benign musculoskeletal disorders are organized by benign cell proliferation/dysplasia, diabetic foot complications, joint prostheses, degeneration, inflammation, and trauma, metabolic bone disorders, and pain (acute and chronic) and peripheral nerve imaging.

  View details for PubMedID 30420212

• PET-MRI for the Study of Metabolic Bone Disease. Current osteoporosis reports Yoder, J. S., Kogan, F., Gold, G. E. 2018

  Abstract

  PURPOSE OF REVIEW: This review article attempts to summarize the current state and applications of the hybrid imaging modality of PET-MRI to metabolic bone diseases. The advances of PET and MRI are also discussed for metabolic bone diseases as potentially applied via PET-MRI.RECENT FINDINGS: Etiologies and mechanisms of metabolic bone disease can be complex where molecular changes precede structural changes. Although PET-MRI has yet to be applied directly to metabolic bone disease, possible applications exist since PET, specifically 18F-NaF PET, can quantitatively track changes in bone metabolism and is useful for assessing treatment, while MRI can give detailed information on bone water concentration, porosity, and architecture through novel techniques such as UTE and ZTE MRI. Earlier detection and further understanding of metabolic bone disease via PET and MRI could lead to better treatment and prevention. More research using this modality is needed to further understand how it can be implemented in this realm.

  View details for PubMedID 30284705

• Applications of PET-MRI in musculoskeletal disease. Journal of magnetic resonance imaging : JMRI Kogan, F., Broski, S. M., Yoon, D., Gold, G. E. 2018; 48 (1): 27–47

  Abstract

  New integrated PET-MRI systems potentially provide a complete imaging modality for diagnosis and evaluation of musculoskeletal disease. MRI is able to provide excellent high-resolution morphologic information with multiple contrast mechanisms that has made it the imaging modality of choice in evaluation of many musculoskeletal disorders. PET offers incomparable abilities to provide quantitative information about molecular and physiologic changes that often precede structural and biochemical changes. In combination, hybrid PET-MRI can enhance imaging of musculoskeletal disorders through early detection of disease as well as improved diagnostic sensitivity and specificity. The purpose of this article is to review emerging applications of PET-MRI in musculoskeletal disease. Both clinical applications of malignant musculoskeletal disease as well as new opportunities to incorporate the molecular capabilities of nuclear imaging into studies of nononcologic musculoskeletal disease are discussed. Lastly, we discuss some of the technical considerations and challenges of PET-MRI as they specifically relate to musculoskeletal disease.LEVEL OF EVIDENCE: 5 TECHNICAL EFFICACY: Stage 3 J. Magn. Reson. Imaging 2018;48:27-47.

  View details for PubMedID 29969193

• Super-resolution musculoskeletal MRI using deep learning. Magnetic resonance in medicine Chaudhari, A. S., Fang, Z., Kogan, F., Wood, J., Stevens, K. J., Gibbons, E. K., Lee, J. H., Gold, G. E., Hargreaves, B. A. 2018

  Abstract

  PURPOSE: To develop a super-resolution technique using convolutional neural networks for generating thin-slice knee MR images from thicker input slices, and compare this method with alternative through-plane interpolation methods.METHODS: We implemented a 3D convolutional neural network entitled DeepResolve to learn residual-based transformations between high-resolution thin-slice images and lower-resolution thick-slice images at the same center locations. DeepResolve was trained using 124 double echo in steady-state (DESS) data sets with 0.7-mm slice thickness and tested on 17 patients. Ground-truth images were compared with DeepResolve, clinically used tricubic interpolation, and Fourier interpolation methods, along with state-of-the-art single-image sparse-coding super-resolution. Comparisons were performed using structural similarity, peak SNR, and RMS error image quality metrics for a multitude of thin-slice downsampling factors. Two musculoskeletal radiologists ranked the 3 data sets and reviewed the diagnostic quality of the DeepResolve, tricubic interpolation, and ground-truth images for sharpness, contrast, artifacts, SNR, and overall diagnostic quality. Mann-Whitney U tests evaluated differences among the quantitative image metrics, reader scores, and rankings. Cohen's Kappa (kappa) evaluated interreader reliability.RESULTS: DeepResolve had significantly better structural similarity, peak SNR, and RMS error than tricubic interpolation, Fourier interpolation, and sparse-coding super-resolution for all downsampling factors (p<.05, except 4*and 8*sparse-coding super-resolution downsampling factors). In the reader study, DeepResolve significantly outperformed (p<.01) tricubic interpolation in all image quality categories and overall image ranking. Both readers had substantial scoring agreement (kappa=0.73).CONCLUSION: DeepResolve was capable of resolving high-resolution thin-slice knee MRI from lower-resolution thicker slices, achieving superior quantitative and qualitative diagnostic performance to both conventionally used and state-of-the-art methods.

  View details for PubMedID 29582464

• Volumetric Multislice GagCEST Imaging of Articular Cartilage: Optimization and Comparison With T1rho MAGNETIC RESONANCE IN MEDICINE Kogan, F., Hargreaves, B. A., Gold, G. E. 2017; 77 (3): 1134-1141

  Abstract

  To develop and optimize a multislice glycosaminoglycan (GAG) chemical exchange saturation transfer (GagCEST) sequence for volumetric imaging of articular cartilage, and to validate the sequence against T1ρ relaxation times in whole joint imaging of tibiotalar cartilage.Ex vivo experiments were used to observe the effect of the number of partitions and shot TR on signal-to-noise ratio and measured GagCESTasym . GagCEST imaging of the entire tibiotalar joint was also performed on 10 healthy subjects. The measured GagCESTasym was compared and correlated with T1ρ relaxation times.Ex vivo studies showed a higher average GagCESTasym from articular cartilage on multislice acquisitions acquired with two or more partitions than observed with a single-slice acquisition. In healthy human subjects, an average GagCESTasym of 8.8 ± 0.7% was observed. A coefficient of variation of GagCESTasym across slices of less than 15% was seen for all subjects. Across subjects, a Pearson correlation coefficient of -0.58 was observed between the measured gagCESTasym and T1ρ relaxation times.We demonstrated the feasibility and optimization of multislice GagCEST mapping of articular cartilage. Volumetric analysis and decreased scan times will help to advance the clinical utility of GagCEST imaging of articular cartilage. Magn Reson Med, 2016. © 2016 Wiley Periodicals, Inc.

  View details for DOI 10.1002/mrm.26200

  View details for Web of Science ID 000397407800022

• Perfusion has no effect on the in vivo CEST effect from Cr (CrCEST) in skeletal muscle. NMR in biomedicine Kogan, F., Stafford, R. B., Englund, E. K., Gold, G. E., Hariharan, H., Detre, J. A., Reddy, R. 2017; 30 (1)

  Abstract

  Creatine, a key component of muscle energy metabolism, exhibits a chemical exchange saturation transfer (CEST) effect between its amine group and bulk water, which has been exploited to spatially and temporally map creatine changes in skeletal muscle before and after exercise. In addition, exercise leads to an increase in muscle perfusion. In this work, we determined the effects of perfused blood on the CEST effects from creatine in skeletal muscle. Experiments were performed on healthy human subjects (n = 5) on a whole-body Siemens 7T magnetic resonance imaging (MRI) scanner with a 28-channel radiofrequency (RF) coil. Reactive hyperemia, induced by inflation and subsequent deflation of a pressure cuff secured around the thigh, was used to increase tissue perfusion whilst maintaining the levels of creatine kinase metabolites. CEST, arterial spin labeling (ASL) and (31) P MRS data were acquired at baseline and for 6 min after cuff deflation. Reactive hyperemia resulted in substantial increases in perfusion in human skeletal muscle of the lower leg as measured by the ASL mean percentage difference. However, no significant changes in CrCEST asymmetry (CrCESTasym ) or (31) P MRS-derived PCr levels of skeletal muscle were observed following cuff deflation. This work demonstrates that perfusion changes do not have a major confounding effect on CrCEST measurements.

  View details for DOI 10.1002/nbm.3673

  View details for PubMedID 27898185

• Potential of PET-MRI for imaging of non-oncologic musculoskeletal disease. Quantitative imaging in medicine and surgery Kogan, F., Fan, A. P., Gold, G. E. 2016; 6 (6): 756-771

  Abstract

  Early detection of musculoskeletal disease leads to improved therapies and patient outcomes, and would benefit greatly from imaging at the cellular and molecular level. As it becomes clear that assessment of multiple tissues and functional processes are often necessary to study the complex pathogenesis of musculoskeletal disorders, the role of multi-modality molecular imaging becomes increasingly important. New positron emission tomography-magnetic resonance imaging (PET-MRI) systems offer to combine high-resolution MRI with simultaneous molecular information from PET to study the multifaceted processes involved in numerous musculoskeletal disorders. In this article, we aim to outline the potential clinical utility of hybrid PET-MRI to these non-oncologic musculoskeletal diseases. We summarize current applications of PET molecular imaging in osteoarthritis (OA), rheumatoid arthritis (RA), metabolic bone diseases and neuropathic peripheral pain. Advanced MRI approaches that reveal biochemical and functional information offer complementary assessment in soft tissues. Additionally, we discuss technical considerations for hybrid PET-MR imaging including MR attenuation correction, workflow, radiation dose, and quantification.

  View details for DOI 10.21037/qims.2016.12.16

  View details for PubMedID 28090451

• T-2 Relaxation time quantitation differs between pulse sequences in articular cartilage JOURNAL OF MAGNETIC RESONANCE IMAGING Matzat, S. J., McWalter, E. J., Kogan, F., Chen, W., Gold, G. E. 2015; 42 (1): 105-113

  Abstract

  To compare T2 relaxation time measurements between MR pulse sequences at 3 Tesla in agar phantoms and in vivo patellar, femoral, and tibial articular cartilage.T2 relaxation times were quantified in phantoms and knee articular cartilage of eight healthy individuals using a single echo spin echo (SE) as a reference standard and five other pulse sequences: multi-echo SE (MESE), fast SE (2D-FSE), magnetization-prepared spoiled gradient echo (3D-MAPSS), three-dimensional (3D) 3D-FSE with variable refocusing flip angle schedules (3D vfl-FSE), and quantitative double echo steady state (qDESS). Cartilage was manually segmented and average regional T2 relaxation times were obtained for each sequence. A regression analysis was carried out between each sequence and the reference standard, and root-mean-square error (RMSE) was calculated.Phantom measurements from all sequences demonstrated strong fits (R(2)  > 0.8; P < 0.05). For in vivo cartilage measurements, R(2) values, slope, and RMSE were: MESE: 0.25/0.42/5.0 ms, 2D-FSE: 0.64/1.31/9.3 ms, 3D-MAPSS: 0.51/0.66/3.8 ms, 3D vfl-FSE: 0.30/0.414.2 ms, qDESS: 0.60/0.90/4.6 ms.2D-FSE, qDESS, and 3D-MAPSS demonstrated the best fits with SE measurements as well as the greatest dynamic ranges. The 3D-MAPSS, 3D vfl-FSE, and qDESS demonstrated the closest average measurements to SE. Discrepancies in T2 relaxation time quantitation between sequences suggest that care should be taken when comparing results between studies.J. Magn. Reson. Imaging 2014. © 2014 Wiley Periodicals, Inc.

  View details for DOI 10.1002/jmri.24757

  View details for Web of Science ID 000356625500012

  View details for PubMedID 25244647

• Imaging strategies for assessing cartilage composition in osteoarthritis. Current rheumatology reports Matzat, S. J., Kogan, F., Fong, G. W., Gold, G. E. 2014; 16 (11): 462-?

  Abstract

  Efforts to reduce the ever-increasing rates of osteoarthritis (OA) in the developed world require the ability to non-invasively detect the degradation of joint tissues before advanced damage has occurred. This is particularly relevant for damage to articular cartilage because this soft tissue lacks the capacity to repair itself following major damage and is essential to proper joint function. While conventional magnetic resonance imaging (MRI) provides sufficient contrast to visualize articular cartilage morphology, more advanced imaging strategies are necessary for understanding the underlying biochemical composition of cartilage that begins to break down in the earliest stages of OA. This review discusses the biochemical basis and the advantages and disadvantages associated with each of these techniques. Recent implementations for these techniques are touched upon, and future considerations for improving the research and clinical power of these imaging technologies are also discussed.

  View details for DOI 10.1007/s11926-014-0462-3

  View details for PubMedID 25218737

  View details for PubMedCentralID PMC4322897

• In Vivo Chemical Exchange Saturation Transfer Imaging of Creatine (CrCEST) in Skeletal Muscle at 3T JOURNAL OF MAGNETIC RESONANCE IMAGING Kogan, F., Haris, M., Debrosse, C., Singh, A., Nanga, R. P., Cai, K., Hariharan, H., Reddy, R. 2014; 40 (3): 596-602

  Abstract

  To characterize the chemical exchange saturation transfer (CEST)-based technique to measure free creatine (Cr), a key component of muscle energy metabolism, distribution in skeletal muscle with high spatial resolution before and after exercise at 3T.CrCEST saturation parameters were empirically optimized for 3T. CEST, T2 , magnetization transfer ratio (MTR), and (31) P magnetic resonance spectroscopy (MRS) acquisitions of the lower leg were performed before and after mild plantar flexion exercise on a 3T whole-body MR scanner on six healthy volunteers.The feasibility of imaging Cr changes in skeletal muscle following plantar flexion exercise using CrCEST was demonstrated at 3T. This technique exhibited good spatial resolution and was able to differentiate differences in muscle use among subjects. The CrCEST results were compared with (31) P MRS results, showing good agreement in the Cr and PCr recovery kinetics. A relationship of 0.45% CrCESTasym /mM Cr was observed across all subjects.It is demonstrated that the CrCEST technique could be applied at 3T to measure dynamic changes in creatine in muscle in vivo. The widespread availability and clinical applicability of 3T scanners has the potential to clinically advance this method.

  View details for DOI 10.1002/jmri.24412

  View details for Web of Science ID 000340538200011

  View details for PubMedID 24925857

• In vivo Magnetic Resonance Imaging of Tumor Protease Activity SCIENTIFIC REPORTS Haris, M., Singh, A., Mohammed, I., Ittyerah, R., Nath, K., Nanga, R. P., Debrosse, C., Kogan, F., Cai, K., Poptani, H., Reddy, D., Hariharan, H., Reddy, R. 2014; 4

  Abstract

  Increased expression of cathepsins has diagnostic as well as prognostic value in several types of cancer. Here, we demonstrate a novel magnetic resonance imaging (MRI) method, which uses poly-L-glutamate (PLG) as an MRI probe to map cathepsin expression in vivo, in a rat brain tumor model. This noninvasive, high-resolution and non-radioactive method exploits the differences in the CEST signals of PLG in the native form and cathepsin mediated cleaved form. The method was validated in phantoms with known physiological concentrations, in tumor cells and in an animal model of brain tumor along with immunohistochemical analysis. Potential applications in tumor diagnosis and evaluation of therapeutic response are outlined.

  View details for DOI 10.1038/srep06081

  View details for Web of Science ID 000340711400001

  View details for PubMedID 25124082

• High Resolution T1 rho Mapping of In Vivo Human Knee Cartilage at 7T PLOS ONE Singh, A., Haris, M., Cai, K., Kogan, F., Hariharan, H., Reddy, R. 2014; 9 (5)

  Abstract

  Spin lattice relaxation time in rotating frame (T1ρ) mapping of human knee cartilage has shown promise in detecting biochemical changes during osteoarthritis. Due to higher field strength, MRI at 7T has advantages in term of SNR compared to clinical MR scanners and this can be used to increase in image resolution. Objective of current study was to evaluate the feasibility of high resolution T1ρ mapping of in vivo human knee cartilage at 7T MR scanner.In this study we have used a T1ρ prepared GRE pulse sequence for obtaining high resolution (in plan resolution  = 0.2 mm2) T1ρ MRI of human knee cartilage at 7T. The effect of a global and localized reference frequency and reference voltage setting on B0, B1 and T1ρ maps in cartilage was evaluated. Test-retest reliability results of T1ρ values from asymptomatic subjects as well as T1ρ maps from abnormal cartilage of two human subjects are presented. These results are compared with T1ρ MRI data obtained from 3T.Our approach enabled acquisition of 3D-T1ρ data within allowed SAR limits at 7T. SNR of cartilage on T1ρ weighted images was greater than 90. Off-resonance effects present in the cartilage B0, B1 and T1ρ maps obtained using global shim and reference frequency and voltage setting, were reduced by the proposed localized reference frequency and voltage setting. T1ρ values of cartilage obtained with the localized approach were reproducible. Abnormal knee cartilage showed elevated T1ρ values in affected regions. T1ρ values at 7T were significantly lower (p<0.05) compared to those obtained at 3T.In summary, by using proposed localized frequency and voltage setting approach, high-resolution 3D-T1ρ maps of in vivo human knee cartilage can be obtained in clinically acceptable scan times (<30 min) and SAR constraints, which provides the ability to characterize cartilage molecular integrity.

  View details for DOI 10.1371/journal.pone.0097486

  View details for Web of Science ID 000336789500067

  View details for PubMedID 24830386

• Imaging of glutamate in the spinal cord using GluCEST NEUROIMAGE Kogan, F., Singh, A., Debrosse, C., Haris, M., Cai, K., Nanga, R. P., Elliott, M., Hariharan, H., Reddy, R. 2013; 77: 262-267

  Abstract

  Glutamate (Glu) is the most abundant excitatory neurotransmitter in the brain and spinal cord. The concentration of Glu is altered in a range of neurologic disorders that affect the spinal cord including multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS) and spinal cord injury. Currently available magnetic resonance spectroscopy (MRS) methods for measuring Glu are limited to low spatial resolution, which makes it difficult to measure differences in gray and white matter glutamate. Recently, it has been shown that Glu exhibits a concentration dependent chemical exchange saturation transfer (CEST) effect between its amine (-NH2) group protons and bulk water protons (GluCEST). Here, we demonstrate the feasibility of imaging glutamate in the spinal cord at 7T using the GluCEST technique. Results from healthy human volunteers (N=7) showed a significantly higher (p<0.001) GluCESTasym from gray matter (6.6±0.3%) compared to white matter (4.8±0.4%). Potential overlap of CEST signals from other spinal cord metabolites with the observed GluCESTasym is discussed. This noninvasive approach potentially opens the way to image Glu in vivo in the spinal cord and to monitor its alteration in many disease conditions.

  View details for DOI 10.1016/j.neuroimage.2013.03.072

  View details for Web of Science ID 000320073900026

  View details for PubMedID 23583425

  View details for PubMedCentralID PMC3804007

• Chemical Exchange Saturation Transfer (CEST) Imaging: Description of Technique and Potential Clinical Applications. Current radiology reports Kogan, F., Hariharan, H., Reddy, R. 2013; 1 (2): 102-114

  Abstract

  Chemical exchange saturation transfer (CEST) is a magnetic resonance imaging (MRI) contrast enhancement technique that enables indirect detection of metabolites with exchangeable protons. Endogenous metabolites with exchangeable protons including many endogenous proteins with amide protons, glycosaminoglycans (GAG), glycogen, myo-inositol (MI), glutamate (Glu), creatine (Cr) and several others have been identified as potential in vivo endogenous CEST agents. These endogenous CEST agents can be exploited as non-invasive and non-ionizing biomarkers of disease diagnosis and treatment monitoring. This review focuses on the recent technical developments in endogenous in vivo CEST MRI from various metabolites as well as their potential clinical applications. The basic underlying principles of CEST, its potential limitations and new techniques to mitigate them are discussed.

  View details for DOI 10.1007/s40134-013-0010-3

  View details for PubMedID 23730540

  View details for PubMedCentralID PMC3665411

• MICEST: A potential tool for non-invasive detection of molecular changes in Alzheimer's disease JOURNAL OF NEUROSCIENCE METHODS Haris, M., Singh, A., Cai, K., Nath, K., Crescenzi, R., Kogan, F., Hariharan, H., Reddy, R. 2013; 212 (1): 87-93

  Abstract

  Myo-inositol (mIns) is a marker of glial cells proliferation and has been shown to increase in early Alzheimer's disease (AD) pathology. mIns exhibits a concentration dependent chemical-exchange-saturation-transfer (CEST) effect (MICEST) between its hydroxyl groups and bulk water protons. Using the endogenous MICEST technique brain mIns concentration and glial cells proliferation can be mapped at high spatial resolution. The high resolution mapping of mIns was performed using MICEST technique on ∼20 months old APP-PS1 transgenic mouse model of AD as well as on age matched wild type (WT) control (n=5). The APP-PS1 mice show ∼50% higher MICEST contrast than WT control with concomitant increase in mIns concentration as measured through proton spectroscopy. Immunostaining against glial-fibric-acidic protein also depicts proliferative glial cells in larger extent in APP-PS1 than WT mice, which correspond to the higher mIns concentration. Potential significance of MICEST in early detection of AD pathology is discussed in detail.

  View details for DOI 10.1016/j.jneumeth.2012.09.025

  View details for Web of Science ID 000313390600009

  View details for PubMedID 23041110

• Exchange rates of creatine kinase metabolites: feasibility of imaging creatine by chemical exchange saturation transfer MRI NMR IN BIOMEDICINE Haris, M., Nanga, R. P., Singh, A., Cai, K., Kogan, F., Hariharan, H., Reddy, R. 2012; 25 (11): 1305-1309

  Abstract

  Creatine (Cr), phosphocreatine (PCr) and adenosine-5-triphosphate (ATP) are major metabolites of the enzyme creatine kinase (CK). The exchange rate of amine protons of CK metabolites at physiological conditions has been limited. In the current study, the exchange rate and logarithmic dissociation constant (pKa) of amine protons of CK metabolites were calculated. Further, the chemical exchange saturation transfer effect (CEST) of amine protons of CK metabolites with bulk water was explored. At physiological temperature and pH, the exchange rate of amine protons in Cr was found to be 7-8 times higher than PCr and ATP. A higher exchange rate in Cr was associated with lower pKa value, suggesting faster dissociation of its amine protons compared to PCr and ATP. CEST MR imaging of these metabolites in vitro in phantoms displayed predominant CEST contrast from Cr and negligible contribution from PCr and ATP with the saturation pulse parameters used in the current study. These results provide a new method to perform high-resolution proton imaging of Cr without contamination from PCr. Potential applications of these finding are discussed.

  View details for DOI 10.1002/nbm.2792

  View details for Web of Science ID 000310237400013

  View details for PubMedID 22431193

• Imaging of glutamate neurotransmitter alterations in Alzheimer's disease. NMR in biomedicine Haris, M., Nath, K., Cai, K., Singh, A., Crescenzi, R., Kogan, F., Verma, G., Reddy, S., Hariharan, H., Melhem, E. R., Reddy, R. 2012

  Abstract

  Glutamate (Glu) is a major excitatory neurotransmitter in the brain and has been shown to decrease in the early stages of Alzheimer's disease (AD). Using a glutamate chemical (amine) exchange saturation transfer (GluCEST) method, we imaged the change in [Glu] in the APP-PS1 transgenic mouse model of AD at high spatial resolution. Compared with wild-type controls, AD mice exhibited a notable reduction in GluCEST contrast (~30%) in all areas of the brain. The change in [Glu] was further validated through (1) H MRS. A positive correlation was observed between GluCEST contrast and (1) H MRS-measured Glu/total creatine ratio. This method potentially provides a novel noninvasive biomarker for the diagnosis of the disease in preclinical stages and enables the development of disease-modifying therapies for AD. Copyright © 2012 John Wiley & Sons, Ltd.

  View details for DOI 10.1002/nbm.2875

  View details for PubMedID 23045158

  View details for PubMedCentralID PMC3556355

• Chemical exchange saturation transfer magnetic resonance imaging of human knee cartilage at 3 T and 7 T MAGNETIC RESONANCE IN MEDICINE Singh, A., Haris, M., Cai, K., Kassey, V. B., Kogan, F., Reddy, D., Hariharan, H., Reddy, R. 2012; 68 (2): 588-594

  Abstract

  The sensitivity of chemical exchange saturation transfer (CEST) on glycosaminoglycans (GAGs) in human knee cartilage (gagCEST) in vivo was evaluated at 3 and 7 T field strengths. Calculated gagCEST values without accounting for B(0) inhomogeneity (~0.6 ppm) were >20%. After B(0) inhomogeneity correction, calculated gagCEST values were negligible at 3 T and ~6% at 7 T. These results suggest that accurate B(0) correction is a prerequisite for observing reliable gagCEST. Results obtained with varying saturation pulse durations and amplitudes as well as the consistency between numerical simulations and our experimental results indicate that the negligible gagCEST observed at 3 T is due to direct saturation effects and fast exchange rate. As GAG loss from cartilage is expected to result in a further reduction in gagCEST, gagCEST method is not expected to be clinically useful at 3 T. At high fields such as 7 T, this method holds promise as a viable clinical technique.

  View details for DOI 10.1002/mrm.23250

  View details for Web of Science ID 000306318900031

  View details for PubMedID 22213239

• Investigation of chemical exchange at intermediate exchange rates using a combination of chemical exchange saturation transfer (CEST) and spin-locking methods (CESTrho) MAGNETIC RESONANCE IN MEDICINE Kogan, F., Singh, A., Cai, K., Haris, M., Hariharan, H., Reddy, R. 2012; 68 (1): 107-119

  Abstract

  Proton exchange imaging is important as it allows for visualization and quantification of the distribution of specific metabolites with conventional MRI. Current exchange mediated MRI methods suffer from poor contrast as well as confounding factors that influence exchange rates. In this study we developed a new method to measure proton exchange which combines chemical exchange saturation transfer and T(1)(ρ) magnetization preparation methods (CESTrho). We demonstrated that this new CESTrho sequence can detect proton exchange in the slow to intermediate exchange regimes. It has a linear dependence on proton concentration which allows it to be used to quantitatively measure changes in metabolite concentration. Additionally, the magnetization scheme of this new method can be customized to make it insensitive to changes in exchange rate while retaining its dependency on solute concentration. Finally, we showed the feasibility of using CESTrho in vivo. This sequence is able to detect proton exchange at intermediate exchange rates and is unaffected by the confounding factors that influence proton exchange rates thus making it ideal for the measurement of metabolites with exchangeable protons in this exchange regime.

  View details for DOI 10.1002/mrm.23213

  View details for Web of Science ID 000305119100011

  View details for PubMedID 22009759