Dr. Kogan is an Assistant Professor with a research focus on imaging of musculoskeletal function and disease. He earned his PhD in Bioengineering at the University of Pennsylvania in 2013 during which he received a HHMI interfaces fellowship and completed the pre-clinical academic curriculum at the UPenn School of Medicine. Afterwards, he did his postdoctoral fellowship in the Radiology Department at Stanford. His group is focused on the development of early markers of disease with novel imaging methods, and the translation of these methods to produce actionable information to impact patient outcomes. He has extensive experience with cutting-edge imaging technologies including multimodal PET-MRI systems, novel quantitative imaging biomarkers and Ultra-high magnetic field (7T). In addition to research, Dr. Kogan has taught lectures in numerous courses at Stanford. He is a junior fellow of the International Society for Magnetic Resonance in Medicine and a member of Council of Early Investigators in Imaging of the Academy for Radiology & Biomedical Imaging Research.
Assistant Professor (Research), Radiology
Honors & Awards
NIBIB Pathway to Independence Award (K99/R00), National Institute of Health (NIH) (2017)
Young Investigator Cum Laude Award (W. S. Moore Award Finalist), International Society of Magnetic Resonance in Medicine (2017)
ISMRM Junior Fellow, International Society of Magnetic Resonance in Medicine (2015)
National Institute of Biomedical Imaging and Bioengineering (NIBIB) Training Grant, National Institute of Health (NIH) (2010)
HHMI Interfaces Fellowship in Imaging Sciences, Howard Hughes Medical Institute (HHMI) (2007)
Young Investigator Award, International Workshop on Osteoarthritis Imaging (2017)
Distinguished Reviewer, Journal of Magnetic Resonance Imaging (2016, 2017)
Editors Recognition Award (Top 10 Most Downloaded Articles), Current Radiology Reports (2016)
Editors Pick Article, Magnetic Resonance in Medicine (2015)
Merit Award for Highest Scoring Trainee Abstract, International Workshop on OA Imaging (IWOAI) (2015)
Magna Cum Laude Merit Award, International Society of Magnetic Resonance in Medicine (2013)
Summa Cum Laude Merit Award, International Society of Magnetic Resonance in Medicine (2012, 2015)
Graduate Fellowship (Honorable Mention), National Science Foundation (NSF) (2007)
B.S, University of Rochester, Optics, Applied Math (2007)
Ph.D, University of Pennsylvania, Bioengineering (2013)
Postdoctoral Fellowship, Stanford University, Radiology (2015)
Current Research and Scholarly Interests
My research is focused on the development and clinical translation of novel quantitative and molecularly specific imaging technologies geared toward detection of disease at the earliest causative stages. Specifically, I am motivated to study the causes and treatment of osteoarthritis (OA) and other musculoskeletal disorders, which have a large physical and financial impact but remain poorly understood. Research projects include development of (1) novel PET and MRI imaging methods to study early tissue changes at the cellular and molecular level, (2) functional imaging methods to study important relationships between mechanics, physiology and tissue microstructure, (3) rapid, comprehensive and quantitative MRI methods for early, low-cost, and precise detection of musculoskeletal disease.
Quantitative imaging of bone-cartilage interactions in ACL-injured patients with PET-MRI.
Osteoarthritis and cartilage
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
2017; 45 (6): 1736-1745
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
Method for high-resolution imaging of creatine in vivo using chemical exchange saturation transfer.
Magnetic resonance in medicine
2014; 71 (1): 164-172
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
A technique for in vivo mapping of myocardial creatine kinase metabolism.
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
Imaging of glutamate in the spinal cord using GluCEST
2013; 77: 262-267
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
Magnetic resonance imaging of glutamate
2012; 18 (2): 302-306
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
Assessment of acute bone loading in humans using [18F]NaF PET/MRI.
European journal of nuclear medicine and molecular imaging
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
- 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 2019; 49 (7): E183–E194
- Kinetic [F-18]-Fluoride of the Knee in Normal Volunteers CLINICAL NUCLEAR MEDICINE 2019; 44 (5): 377–85
Applications of PET-Computed Tomography-Magnetic Resonance in the Management of Benign Musculoskeletal Disorders.
2019; 14 (1): 1–15
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
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
2018; 48 (1): 27–47
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
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
Simultaneous bilateral-knee MR imaging.
Magnetic resonance in medicine
2018; 80 (2): 529–37
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
2018; 26 (6): 790-796
View details for DOI 10.1016/j.joca.2018.04.001
Volumetric Multislice GagCEST Imaging of Articular Cartilage: Optimization and Comparison With T1rho
MAGNETIC RESONANCE IN MEDICINE
2017; 77 (3): 1134-1141
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
2017; 30 (1)
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
2016; 6 (6): 756-771
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
2015; 42 (1): 105-113
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
2014; 16 (11): 462-?
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
2014; 40 (3): 596-602
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
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
2014; 9 (5)
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
MICEST: A potential tool for non-invasive detection of molecular changes in Alzheimer's disease
JOURNAL OF NEUROSCIENCE METHODS
2013; 212 (1): 87-93
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
Chemical Exchange Saturation Transfer (CEST) Imaging: Description of Technique and Potential Clinical Applications.
Current radiology reports
2013; 1 (2): 102–14
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
Exchange rates of creatine kinase metabolites: feasibility of imaging creatine by chemical exchange saturation transfer MRI
NMR IN BIOMEDICINE
2012; 25 (11): 1305-1309
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
Chemical exchange saturation transfer magnetic resonance imaging of human knee cartilage at 3 T and 7 T
MAGNETIC RESONANCE IN MEDICINE
2012; 68 (2): 588-594
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
2012; 68 (1): 107-119
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
Imaging of glutamate neurotransmitter alterations in Alzheimer's disease.
NMR in biomedicine
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