[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.

Denervation during mandibular distraction osteogenesis results in impaired bone formation.

Mandibular distraction osteogenesis (DO) is mediated by skeletal stem cells (SSCs) in mice, which enact bone regeneration via neural crest re-activation. As peripheral nerves are essential to progenitor function during development and in response to injury, we questioned if denervation impairs mandibular DO. C57Bl6 mice were divided into two groups: DO with a segmental defect in the inferior alveolar nerve (IAN) at the time of mandibular osteotomy ("DO Den") and DO with IAN intact ("DO Inn"). DO Den demonstrated significantly reduced histological and radiological osteogenesis relative to DO Inn. Denervation preceding DO results in reduced SSC amplification and osteogenic potential in mice. Single cell RNA sequencing analysis revealed that there was a predominance of innervated SSCs in clusters dominated by pathways related to bone formation. A rare human patient specimen was also analyzed and suggested that histological, radiological, and transcriptional alterations seen in mouse DO may be conserved in the setting of denervated human mandible distraction. Fibromodulin (FMOD) transcriptional and protein expression were reduced in denervated relative to innervated mouse and human mandible regenerate. Finally, when exogenous FMOD was added to DO-Den and DO-Inn SSCs undergoing in vitro osteogenic differentiation, the osteogenic potential of DO-Den SSCs was increased in comparison to control untreated DO-Den SSCs, modeling the superior osteogenic potential of DO-Inn SSCs.

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.

Kinetic [18F]-Fluoride of the Knee in Normal Volunteers.

PURPOSE: [F]-sodium fluoride ([F]NaF) is a well-established bone-seeking agent that has shown promise to assess bone turnover in a variety of disorders, but its distribution in healthy knee joints has not been explored. This study aimed to investigate parametric values for [F]NaF uptake in various bone tissues types of the knee and their spatial distributions. METHODS: Twelve healthy subjects were hand-injected with 92.5 MBq of [F]NaF and scanned on a 3-T PET/MRI system. Listmode PET data for both knees were acquired for 50 minutes from injection simultaneously with MRI Dixon and angiography data. The image-derived input function was determined from the popliteal artery. Using the Hawkins model, Patlak analysis was performed to obtain Ki (Ki) values and nonlinear regression analysis to obtain Ki, K1, k3/(k2 + k3), and blood volume. Comparisons for the measured kinetic parameters, SUV, and SUVmax were made between tissue types (subchondral, cortical, and trabecular bone) and between regional subsections of subchondral bone. RESULTS: Cortical bone had the highest [F]NaF uptake differing significantly in all measured parameters when compared with trabecular bone and significantly higher SUVmax and K1 than subchondral bone. Subchondral bone also had significantly higher SUV, SUVmax, and Ki than trabecular bone tissue. Regional differences were observed in K1 and k3/(k2 + k3) values. CONCLUSIONS: Quantitative [F]NaF PET is sensitive to variations in bone vascularization and metabolism in the knee joint.