Imaging Bone–Cartilage Interactions in Osteoarthritis Using [¹⁸F]-NaF PET-MRI

Abstract

Purpose:Simultaneous positron emission tomography–magnetic resonance imaging (PET-MRI) is an emerging technology providing both anatomical and functional images without increasing the scan time. Compared to the traditional PET/computed tomography imaging, it also exposes the patient to significantly less radiation and provides better anatomical images as MRI provides superior soft tissue characterization. Using PET-MRI, we aim to study interactions between cartilage composition and bone function simultaneously, in knee osteoarthritis (OA).Procedures:In this article, bone turnover and remodeling was studied using [18F]-sodium fluoride (NaF) PET data. Quantitative MR-derived T1ρ relaxation times characterized the biochemical cartilage degeneration. Sixteen participants with early signs of OA of the knee received intravenous injections of [18F]-NaF at the onset of PET-MR image acquisition. Regions of interest were identified, and kinetic analysis of dynamic PET data provided the rate of uptake (Ki) and the normalized uptake (standardized uptake value) of [18F]-NaF in the bone. Morphological MR images and quantitative voxel-based T1ρ maps of cartilage were obtained using an atlas-based registration technique to segment cartilage automatically. Voxel-by-voxel statistical parameter mapping was used to investigate the relationship between bone and cartilage.Results:Increases in cartilage T1ρ, indicating degenerative changes, were associated with increased turnover in the adjoining bone but reduced turnover in the nonadjoining compartments. Associations between pain and increased bone uptake were seen in the absence of morphological lesions in cartilage, but the relationship was reversed in the presence of incident cartilage lesions.Conclusion:This study shows significant cartilage and bone interactions in OA of the knee joint using simultaneous [18F]-NaF PET-MR, the first in human study. These observations highlight the complex biomechanical and biochemical interactions in the whole knee joint in OA, which potentially could help assess therapeutic targets in treating OA.

The Role of Dot1l in Prenatal and Postnatal Murine Chondrocytes and Trabecular Bone

“…(37,38) Involvement of Dot1l in this process remains to be explored. In addition, in human osteoarthritis, cartilage degenerative changes are associated with increased turnover in the adjoining bone, but reduced turnover in the nonadjoining bone, (39) indicating interaction between cartilage integrity and surrounding bone.…”

Applications of PET‐MRI in musculoskeletal disease

“…Current whole‐joint assessments of OA with MRI largely rely on semi‐quantitative scoring systems, which subjectively evaluate tissue structures . In a study of mild to moderate OA patients, increases in cartilage T 1ρ relaxation times, which are associated with a loss of cartilage GAG content, were correlated with increased 18 F‐NaF uptake in the adjoining bone as well as reduced uptake in the nonadjoining compartments . In a separate study of patients with unilateral, reconstructed ACL tears, a correlation was observed between increased 18 F‐NaF uptake measures of bone remodeling and increased T 2 values in adjacent cartilage, which is indicative of early collagen matrix breakdown .…”

Single-Cell Imaging Using Radioluminescence Microscopy Reveals Unexpected Binding Target for [18F]HFB

“…Previous reports of high labelling efficiency and retention of [ 18 F]HFB over 4 h (77 - 95%) in vitro and in vivo [19,28] suggested the radiolabel may be well suited for monitoring individual cells in vivo using a trajectory reconstruction algorithm developed in-house [20,27]. In vitro bulk labelling of rat mesenchymal stem cells (MSCs) (5 × 10 5 /0.5 mL, 1 mCi, 30 min) indicated labelling efficiency of [ 18 F]HFB was 25% after 4h and [ 18 F]HFB-labelled cells were detected in the lungs 55-60 min post-intravenous injection [19].…”

“…While PEPT is used exclusively for studying chemical and industrial processes, the potential of PEPT for biomedical investigations, such as cell tracking, is increasingly being recognised [26]. To assess the feasibility of tracking a single cell, a novel trajectory reconstruction algorithm was developed in-house and validated using computer simulation and phantom models [20,27]. These simulations predict that labelling a single cell with 20 - 25 Bq (0.54-0.68 nCi) of activity is sufficient for tracking the cell in vivo using small animal PET.…”