We recently showed that patients with different chronic pain conditions (such as chronic low back pain, fibromyalgia, migraine, and Gulf War Illness) demonstrated elevated brain and/or spinal cord levels of the glial marker 18 kDa translocator protein, which suggests that neuroinflammation might be a pervasive phenomenon observable across multiple etiologically heterogeneous pain disorders. Interestingly, the spatial distribution of this neuroinflammatory signal appears to exhibit a degree of disease specificity (e.g. with respect to the involvement of the primary somatosensory cortex), suggesting that different pain conditions may exhibit distinct “neuroinflammatory signatures”. To further explore this hypothesis, we tested whether neuroinflammatory signal can characterize putative etiological subtypes of chronic low back pain patients based on clinical presentation. Specifically, we explored neuroinflammation in patients whose chronic low back pain either did or did not radiate to the leg (i.e. “radicular” vs. “axial” back pain). Fifty-four chronic low back pain patients, twenty-six with axial back pain (43.7 ± 16.6 y.o. [mean±SD]) and twenty-eight with radicular back pain (48.3 ± 13.2 y.o.), underwent PET/MRI with [11C]PBR28, a second-generation radioligand for the 18 kDa translocator protein. [11C]PBR28 signal was quantified using standardized uptake values ratio (validated against volume of distribution ratio; n = 23). Functional MRI data were collected simultaneously to the [11C]PBR28 data 1) to functionally localize the primary somatosensory cortex back and leg subregions and 2) to perform functional connectivity analyses (in order to investigate possible neurophysiological correlations of the neuroinflammatory signal). PET and functional MRI measures were compared across groups, cross-correlated with one another and with the severity of “fibromyalgianess” (i.e. the degree of pain centralization, or “nociplastic pain”). Furthermore, statistical mediation models were employed to explore possible causal relationships between these three variables. For the primary somatosensory cortex representation of back/leg, [11C]PBR28 PET signal and functional connectivity to the thalamus were: 1) higher in radicular compared to axial back pain patients, 2) positively correlated with each other and 3) positively correlated with fibromyalgianess scores, across groups. Finally, 4) fibromyalgianess mediated the association between [11C]PBR28 PET signal and primary somatosensory cortex-thalamus connectivity across groups. Our findings support the existence of “neuroinflammatory signatures” that are accompanied by neurophysiological changes, and correlate with clinical presentation (in particular, with the degree of nociplastic pain) in chronic pain patients. These signatures may contribute to the subtyping of distinct pain syndromes and also provide information about inter-individual variability in neuro-immune brain signals, within diagnostic groups, that could eventually serve as targets for mechanism-based precision medicine approaches.

Positron emission tomography/magnetic resonance imaging (PET/MRI) potentially offers several advantages over positron emission tomography/computed tomography (PET/CT), for example, no CT radiation dose and soft tissue images from MR acquired at the same time as the PET. However, obtaining accurate linear attenuation correction (LAC) factors for the lung remains difficult in PET/MRI. LACs depend on electron density and in the lung, these vary significantly both within an individual and from person to person. Current commercial practice is to use a single‐valued population‐based lung LAC, and better estimation is needed to improve quantification. Given the under‐appreciation of lung attenuation estimation as an issue, the inaccuracy of PET quantification due to the use of single‐valued lung LACs, the unique challenges of lung estimation, and the emerging status of PET/MRI scanners in lung disease, a review is timely. This paper highlights past and present methods, categorizing them into segmentation, atlas/mapping, and emission‐based schemes. Potential strategies for future developments are also presented.

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Estimation of attenuation from PET data only is of interest for PET-MR and systems where CT is not available or recommended. However, when using data from a single energy window, emission-based non-TOF PET attenuation correction (AC) methods suffer from 'cross-talk' artefacts. Based on earlier work, this manuscript explores the hypothesis that cross-talk can be reduced by using more than one energy window. We propose an algorithm for the simultaneous estimation of both activity and attenuation images as well as the scatter component of the measured data from a PET acquisition, using multiple energy windows. The model for the measurements is 3D and accounts for the finite energy resolution of PET detectors; it is restricted to single scatter. The proposed MLAA-EB-S algorithm is compared with simultaneous estimation from a single energy window (MLAA-S). The evaluation is based on simulations using the characteristics of the Siemens mMR scanner. Phantoms of different complexity were investigated. In particular, a 3D XCAT torso phantom was used to assess the inpainting of attenuation values within the lung region. Results show that the crosstalk present in non-TOF MLAA reconstructions is significantly reduced when using multiple energy windows and indicate that the proposed approach warrants further investigation.

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This study explores the feasibility of incorporating energy information into a maximum-likelihood reconstruction of activity and attenuation (MLAA) framework. The attenuation and activity distributions were reconstructed from multiple energy window data, and a scatter function was added to the system model of the algorithm. The proposed energy-based method (MLAA-EB) was evaluated with simulated 3D phantom data, using the geometry and characteristics of a Siemens mMR PET-MR scanner. Results showed that the proposed algorithm is able to compensate for errors in the activity image caused by the incorrect assignment of attenuation values to the segmented MR. This is effective for small objects only, for large objects further solutions need to be found.

Statistical PET image reconstruction methods are often accelerated by the use of a subset of available projections at each iteration. It is known that many subset algorithms, such as ordered subset expectation maximisation, will not converge to a single solution but to a limit cycle. Reconstruction methods exist to relax the update step sizes of subset algorithms to obtain convergence, however, this introduces additional parameters that may result in extended reconstruction times. Another approach is to gradually decrease the number of subsets to reduce the effect of the limit cycle at later iterations, but the optimal iteration numbers for these reductions may be data dependent. We propose an automatic method to increase subset sizes so a reconstruction can take advantage of the acceleration provided by small subset sizes during early iterations, while at later iterations reducing the effects of the limit cycle behaviour providing estimates closer to the maximum a posteriori solution. At each iteration, two image updates are computed from a common estimate using two disjoint subsets. The divergence of the two update vectors is measured and, if too great, subset sizes are increased in future iterations. We show results for both sinogram and list mode data using various subset selection methodologies.