Multimodal positron emission tomography (PET) imaging in non-oncologic musculoskeletal radiology.

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.

Design and rationale of re-energize fontan: Randomized exercise intervention designed to maximize fitness in fontan patients.

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 2 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.

A method for measuring B0 field inhomogeneity using quantitative double-echo in steady-state.

PURPOSE: 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 Î¸ $$ \Delta \theta $$ ) between the two echoes acquired. Contrary to a two-gradient-echo (2-GRE) method, Δ Î¸ $$ \Delta \theta $$ depends only on the first echo time. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Advanced MRI Approaches for Evaluating Common Lower Extremity Injuries in Basketball Players: Current and Emerging Techniques.

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.

Generalizability of Deep Learning Segmentation Algorithms for Automated Assessment of Cartilage Morphology and MRI Relaxometry.

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, ±2.4 msec and ±4.0 msec, than the OAI-DESS-trained model, ±4.4 msec and ±5.2 msec. 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.

Advanced Magnetic Resonance Imaging and Molecular Imaging of the Painful Knee.

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.

[Formula: see text] Field inhomogeneity correction for qDESS [Formula: see text] mapping: application to rapid bilateral knee imaging.

PURPOSE: [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. METHODS: 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]. RESULTS: 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). CONCLUSION: 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.

Imaging of joint response to exercise with MRI and PET.

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.

Gadolinium-free assessment of synovitis using diffusion tensor imaging.

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.

Imaging of Synovial Inflammation in Osteoarthritis, From the AJR Special Series on Inflammation.

Synovitis, inflammation of the synovial membrane, is a common manifestation of 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 its potential as a target for treatment has increased the need for noninvasive detection and characterization of synovitis using medical imaging. Numerous imaging methods can assess synovitis involvement in OA with varying sensitivity, specificity, and 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 and the challenges of conventional imaging methods are discussed. We also provide an overview of 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 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.

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

BACKGROUND: Injuries to the articular cartilage in the knee are common in jumping athletes, particularly high-level basketball players. Unfortunately, these are often diagnosed at a late stage of the disease process, after tissue loss has already occurred. PURPOSE/HYPOTHESIS: To evaluate longitudinal changes in knee articular cartilage and knee function in National Collegiate Athletic Association (NCAA) basketball players and their evolution over the competitive season and off-season. STUDY TYPE: Longitudinal, multisite cohort study. POPULATION: Thirty-two NCAA Division 1 athletes: 22 basketball players and 10 swimmers. FIELD STRENGTH/SEQUENCE: 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. ASSESSMENT: 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. STATISTICAL TESTS: One-way variance model hypothesis test, general linear model, and chi-squared test. RESULTS: 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). CONCLUSION: 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. LEVEL OF EVIDENCE: 2 Technical Efficacy Stage: 2.

Non-contrast MRI of synovitis in the knee using quantitative DESS.

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.

Characterization of Structural Bone Properties through Portable Single-Sided NMR Devices: State of the Art and Future Perspectives.

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.

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

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.

Rapid Knee MRI Acquisition and Analysis Techniques for Imaging Osteoarthritis.

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.

Identifying Musculoskeletal Pain Generators Using Clinical PET.

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.

Assessment of acute bone loading in humans using [18F]NaF PET/MRI.

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.

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.

BACKGROUND: Clinical knee MRI protocols require upwards of 15 minutes of scan time. PURPOSE/HYPOTHESIS: To compare the imaging appearance of knee abnormalities depicted with a 5-minute 3D double-echo in steady-state (DESS) sequence with separate echo images, with that of a routine clinical knee MRI protocol. A secondary goal was to compare the imaging appearance of knee abnormalities depicted with 5-minute DESS paired with a 2-minute coronal proton-density fat-saturated (PDFS) sequence. STUDY TYPE: Prospective. SUBJECTS: Thirty-six consecutive patients (19 male) referred for a routine knee MRI. FIELD STRENGTH/SEQUENCES: DESS and PDFS at 3T. ASSESSMENT: Five musculoskeletal radiologists evaluated all images for the presence of internal knee derangement using DESS, DESS+PDFS, and the conventional imaging protocol, and their associated diagnostic confidence of the reading. STATISTICAL TESTS: Differences in positive and negative percent agreement (PPA and NPA, respectively) and 95% confidence intervals (CIs) for DESS and DESS+PDFS compared with the conventional protocol were calculated and tested using exact McNemar tests. The percentage of observations where DESS or DESS+PDFS had equivalent confidence ratings to DESS+Conv were tested with exact symmetry tests. Interreader agreement was calculated using Krippendorff's alpha. RESULTS: DESS had a PPA of 90% (88-92% CI) and NPA of 99% (99-99% CI). DESS+PDFS had increased PPA of 99% (95-99% CI) and NPA of 100% (99-100% CI) compared with DESS (both P < 0.001). DESS had equivalent diagnostic confidence to DESS+Conv in 94% of findings, whereas DESS+PDFS had equivalent diagnostic confidence in 99% of findings (both P < 0.001). All readers had moderate concordance for all three protocols (Krippendorff's alpha 47-48%). DATA CONCLUSION: Both 1) 5-minute 3D-DESS with separated echoes and 2) 5-minute 3D-DESS paired with a 2-minute coronal PDFS sequence depicted knee abnormalities similarly to a routine clinical knee MRI protocol, which may be a promising technique for abbreviated knee MRI. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018.

Super-resolution musculoskeletal MRI using deep learning.

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 (κ) 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 (κ = 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.