Air Fraction Correction Optimisation in PET Imaging of Lung Disease

Accurate quantification of radiopharmaceutical uptake from lung PET/CT is challenging due to large variations in fractions of tissue, air, blood and water. Air fraction correction (AFC) uses voxel-wise air fractions, which can be determined from the CT acquired for attenuation correction (AC). However, resolution effects can cause artefacts in either of these corrections. In this work, we hypothesise that the resolution of the CT image used for AC should match that of the intrinsic resolution of the PET scanner but should approximate the reconstructed PET image resolution for AFC. Simulations and reconstructions were performed with the Synergistic Image Reconstruction Framework (SIRF) using phantoms with inhomogeneous attenuation (mu) maps, mimicking the densities observed in lung pathologies. Poisson noise was added to the projection data prior to OSEM reconstruction. AC was performed with a smoothed mu-map, the full-width-half-maximum (FWHM) of the 3D Gaussian kernel was varied (0 - 10 mm). Post-filters were applied to the reconstructed AC images (FWHM: 0 - 8 mm). The simulated mu-map was independently convolved with another set of 3D Gaussian kernels, of varying FWHM (0 - 12 mm), for AFC. The coefficient of variation (CV) in the lung region, designed to be homogeneous post-AFC with optimised kernels, and the mean AFC-standardized uptake value (AFC-SUV) in the regions of simulated pathologies were determined. The spatial resolution of each post-filtered image was determined via a point-source insertion-and-subtraction method on noiseless data. Results showed that the CV was minimised when the kernel applied to the mu-map for AC matched that for the simulated PET scanner and the kernel applied to the mu-map for AFC matched the spatial resolution of the reconstructed PET image. This was observed for all post-reconstruction filters and supports the hypothesis. Initial results from Monte Carlo simulations validate these findings

A Demonstration of STIR-GATE-Connection

We present the first open-source version of STIR-GATE-Connection, a project that aims to provide an easy-to-use pipeline to simulate realistic PET data using GATE, followed by quantitative reconstruction using STIR. Monte Carlo simulations and image reconstruction are powerful research tools for emission tomography that can assist with the design of new medical imaging devices as well as the evaluation of novel image reconstruction algorithms and various correction techniques. STIR-GATE-Connection is a collection of scripts that aid with the: (i) setup of a realistic GATE simulation of a voxelised phantom using a user selected scanner configuration, (ii) conversion of the output list mode data into STIR compatible sinograms, and (iii) computation of additive and multiplicative data corrections for Poisson image reconstruction using STIR. In this work, we demonstrate example usage of these steps. A public release of STIR-GATE-Connection, licensed under the Apache 2.0 License, can be downloaded at: http://www.github.com/UCL/STIR-GATE-Connection

Optimisation of the air fraction correction for lung PET/CT: addressing resolution mismatch

Background: Increased pulmonary 18 F-FDG metabolism in patients with idiopathic pulmonary fibrosis, and other forms of diffuse parenchymal lung disease, can predict measurements of health and lung physiology. To improve PET quantification, voxel-wise air fractions (AF) determined from CT can be used to correct for variable air content in lung PET/CT. However, resolution mismatches between PET and CT can cause artefacts in the AF-corrected image. Methods: Three methodologies for determining the optimal kernel to smooth the CT are compared with noiseless simulations and non-TOF MLEM reconstructions of a patient-realistic digital phantom: (i) the point source insertion-and-subtraction method, hpts ; (ii) AF-correcting with varyingly smoothed CT to achieve the lowest RMSE with respect to the ground truth (GT) AF-corrected volume of interest (VOI), hAFC ; iii) smoothing the GT image to match the reconstruction within the VOI, hPVC . The methods were evaluated both using VOI-specific kernels, and a single global kernel optimised for the six VOIs combined. Furthermore, hPVC was implemented on thorax phantom data measured on two clinical PET/CT scanners with various reconstruction protocols. Results: The simulations demonstrated that at < 200 iterations (200 i), the kernel width was dependent on iteration number and VOI position in the lung. The hpts method estimated a lower, more uniform, kernel width in all parts of the lung investigated. However, all three methods resulted in approximately equivalent AF-corrected VOI RMSEs (<10%) at ≥ 200i. The insensitivity of AF-corrected quantification to kernel width suggests that a single global kernel could be used. For all three methodologies, the computed global kernel resulted in an AF-corrected lung RMSE <10% at ≥ 200i, while larger lung RMSEs were observed for the VOI–specific kernels. The global kernel approach was then employed with the hPVC method on measured data. The optimally smoothed GT emission matched the reconstructed image well, both within the VOI and the lung background. VOI RMSE was <10%, pre-AFC, for all reconstructions investigated. Conclusions: Simulations for non-TOF PET indicated that around 200i were needed to approach image resolution stability in the lung. In addition, at this iteration number, a single global kernel, determined from several VOIs, for AFC, performed well over the whole lung. The hPVC method has the potential to be used to determine the kernel for AFC from scans of phantoms on clinical scanners

Cognitive domains affected post-COVID-19; a systematic review and meta-analysis

\ua9 2024 The Authors. European Journal of Neurology published by John Wiley &amp; Sons Ltd on behalf of European Academy of Neurology.Background and purpose: This review aims to characterize the pattern of post-COVID-19 cognitive impairment, allowing better prediction of impact on daily function to inform clinical management and rehabilitation. Methods: A systematic review and meta-analysis of neurocognitive sequelae following COVID-19 was conducted, following PRISMA-S guidelines. Studies were included if they reported domain-specific cognitive assessment in patients with COVID-19 at &gt;4 weeks post-infection. Studies were deemed high-quality if they had &gt;40 participants, utilized healthy controls, had low attrition rates and mitigated for confounders. Results: Five of the seven primary Diagnostic and Statistical Manual of Mental Disorders (DSM-5) cognitive domains were assessed by enough high-quality studies to facilitate meta-analysis. Medium effect sizes indicating impairment in patients post-COVID-19 versus controls were seen across executive function (standardised mean difference (SMD) −0.45), learning and memory (SMD −0.55), complex attention (SMD −0.54) and language (SMD −0.54), with perceptual motor function appearing to be impacted to a greater degree (SMD −0.70). A narrative synthesis of the 56 low-quality studies also suggested no obvious pattern of impairment. Conclusions: This review found moderate impairments across multiple domains of cognition in patients post-COVID-19, with no specific pattern. The reported literature was significantly heterogeneous, with a wide variety of cognitive tasks, small sample sizes and disparate initial disease severities limiting interpretability. The finding of consistent impairment across a range of cognitive tasks suggests broad, as opposed to domain-specific, brain dysfunction. Future studies should utilize a harmonized test battery to facilitate inter-study comparisons, whilst also accounting for the interactions between COVID-19, neurological sequelae and mental health, the interplay between which might explain cognitive impairment

Inflammation and tissue repair markers distinguish the nodular sclerosis and mixed cellularity subtypes of classical Hodgkin's lymphoma

Background: Classical Hodgkin's lymphoma (cHL), although a malignant disease, has many features in common with an inflammatory condition. The aim of this study was to establish the molecular characteristics of the two most common cHL subtypes, nodular sclerosis (NS) and mixed cellularity (MC), based on molecular profiling and immunohistochemistry, with special reference to the inflammatory microenvironment. Methods: We analysed 44 gene expression profiles of cHL whole tumour tissues, 25 cases of NS and 19 cases of MC, using Affymetrix chip technology and immunohistochemistry. Results: In the NS subtype, 152 genes showed a significantly higher expression, including genes involved in extracellular matrix (ECM) remodelling and ECM deposition similar to wound healing. Among these were SPARC, CTSK and COLI. Immunohistochemistry revealed that the NS-related genes were mainly expressed by macrophages and fibroblasts. Fifty-three genes had a higher expression in the MC subtype, including several inflammation-related genes, such as C1Qα, C1Qβ and CXCL9. In MC tissues, the C1Q subunits were mainly expressed by infiltrating macrophages. Conclusions and interpretations: We suggest that the identified subtype-specific genes could reflect different phases of wound healing. Our study underlines the potential function of infiltrating macrophages in shaping the cHL tumour microenvironment

Suppression of charged particle production at large transverse momentum in central Pb-Pb collisions at sNN=2.76\sqrt{s_{\rm NN}} = 2.76 TeV

Inclusive transverse momentum spectra of primary charged particles in Pb-Pb collisions at $\sqrt{s_{_{\rm NN}}}$ = 2.76 TeV have been measured by the ALICE Collaboration at the LHC. The data are presented for central and peripheral collisions, corresponding to 0-5% and 70-80% of the hadronic Pb-Pb cross section. The measured charged particle spectra in $|\eta|<0.8$ and $0.3 < p_T < 20$ GeV/$c$ are compared to the expectation in pp collisions at the same $\sqrt{s_{\rm NN}}$, scaled by the number of underlying nucleon-nucleon collisions. The comparison is expressed in terms of the nuclear modification factor $R_{\rm AA}$. The result indicates only weak medium effects ($R_{\rm AA} \approx$ 0.7) in peripheral collisions. In central collisions, $R_{\rm AA}$ reaches a minimum of about 0.14 at $p_{\rm T}=6$-7GeV/$c$ and increases significantly at larger $p_{\rm T}$. The measured suppression of high-$p_{\rm T}$ particles is stronger than that observed at lower collision energies, indicating that a very dense medium is formed in central Pb-Pb collisions at the LHC.Comment: 15 pages, 5 captioned figures, 3 tables, authors from page 10, published version, figures at http://aliceinfo.cern.ch/ArtSubmission/node/98

Two-pion Bose-Einstein correlations in central Pb-Pb collisions at sNN\sqrt{s_{\rm NN}} = 2.76 TeV

The first measurement of two-pion Bose-Einstein correlations in central Pb-Pb collisions at $\sqrt{s_{\rm NN}} = 2.76$ TeV at the Large Hadron Collider is presented. We observe a growing trend with energy now not only for the longitudinal and the outward but also for the sideward pion source radius. The pion homogeneity volume and the decoupling time are significantly larger than those measured at RHIC.Comment: 17 pages, 5 captioned figures, 1 table, authors from page 12, published version, figures at http://aliceinfo.cern.ch/ArtSubmission/node/388

Hypoxia Potentiates Glioma-Mediated Immunosuppression

Glioblastoma multiforme (GBM) is a lethal cancer that exerts potent immune suppression. Hypoxia is a predominant feature of GBM, but it is unclear to the degree in which tumor hypoxia contributes to this tumor-mediated immunosuppression. Utilizing GBM associated cancer stem cells (gCSCs) as a treatment resistant population that has been shown to inhibit both innate and adaptive immune responses, we compared immunosuppressive properties under both normoxic and hypoxic conditions. Functional immunosuppression was characterized based on production of immunosuppressive cytokines and chemokines, the inhibition of T cell proliferation and effector responses, induction of FoxP3+ regulatory T cells, effect on macrophage phagocytosis, and skewing to the immunosuppressive M2 phenotype. We found that hypoxia potentiated the gCSC-mediated inhibition of T cell proliferation and activation and especially the induction of FoxP3+T cells, and further inhibited macrophage phagocytosis compared to normoxia condition. These immunosuppressive hypoxic effects were mediated by signal transducer and activator of transcription 3 (STAT3) and its transcriptionally regulated products such as hypoxia inducible factor (HIF)-1α and vascular endothelial growth factor (VEGF). Inhibitors of STAT3 and HIF-1α down modulated the gCSCs' hypoxia-induced immunosuppressive effects. Thus, hypoxia further enhances GBM-mediated immunosuppression, which can be reversed with therapeutic inhibition of STAT3 and HIF-1α and also helps to reconcile the disparate findings that immune therapeutic approaches can be used successfully in model systems but have yet to achieve generalized successful responses in the vast majority of GBM patients by demonstrating the importance of the tumor hypoxic environment

Extrinsic primary afferent signalling in the gut

Visceral sensory neurons activate reflex pathways that control gut function and also give rise to important sensations, such as fullness, bloating, nausea, discomfort, urgency and pain. Sensory neurons are organised into three distinct anatomical pathways to the central nervous system (vagal, thoracolumbar and lumbosacral). Although remarkable progress has been made in characterizing the roles of many ion channels, receptors and second messengers in visceral sensory neurons, the basic aim of understanding how many classes there are, and how they differ, has proven difficult to achieve. We suggest that just five structurally distinct types of sensory endings are present in the gut wall that account for essentially all of the primary afferent neurons in the three pathways. Each of these five major structural types of endings seems to show distinctive combinations of physiological responses. These types are: 'intraganglionic laminar' endings in myenteric ganglia; 'mucosal' endings located in the subepithelial layer; 'muscular–mucosal' afferents, with mechanosensitive endings close to the muscularis mucosae; 'intramuscular' endings, with endings within the smooth muscle layers; and 'vascular' afferents, with sensitive endings primarily on blood vessels. 'Silent' afferents might be a subset of inexcitable 'vascular' afferents, which can be switched on by inflammatory mediators. Extrinsic sensory neurons comprise an attractive focus for targeted therapeutic intervention in a range of gastrointestinal disorders.Australian National Health and Medical Research Counci