Brown Adipose Tissue (BAT) is present in a significant number of adult humans and can be activated by exposure to cold. Measurement of active BAT presence, activity, and volume are desirable for ...determining the efficacy of potential treatments intended to activate BAT. The repeatability of 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) measurements of BAT presence, activity, and volume under controlled conditions has not been extensively studied. Eleven female volunteers underwent double baseline FDG PET imaging performed following a simple, regional cold intervention intended to activate brown fat. The cold intervention involved the lightly-clothed participants intermittently placing their feet on a block of ice while sitting in a cooled room. A repeat study was performed under the same conditions within a target of two weeks. FDG scans were obtained and maximum standardized uptake value adjusted for lean body mass (SULmax), CT Hounsfield units (HU), BAT metabolic volume (BMV), and total BAT glycolysis (TBG) were determined according to the Brown Adipose Reporting Criteria in Imaging STudies (BARCIST) 1.0. A Lin's concordance correlation (CCC) of 0.80 was found for BMV between test and retest imaging. Intersession BAT SULmax was significantly correlated (r = 0.54; p < 0.05). The session #1 mean SULmax of 4.92 ± 4.49 g/mL was not significantly different from that of session #2 with a mean SULmax of 7.19 ± 7.34 g/mL (p = 0.16). BAT SULmax was highly correlated with BMV in test and retest studies (r ≥ 0.96, p < 0.001). Using a simplified ice-block cooling method, BAT was activated in the majority (9/11) of a group of young, lean female participants. Quantitative assessments of BAT SUL and BMV were not substantially different between test and retest imaging, but individual BMV could vary considerably. Intrasession BMV and SULmax were strongly correlated. The variability in estimates of BAT activity and volume on test-retest with FDG should inform sample size choice in studies quantifying BAT physiology and support the dynamic metabolic characteristics of this tissue. A more sophisticated cooling method potentially may reduce variations in test-retest BAT studies.
Brown adipose tissue (BAT) was first described in the 16th century, but until late last century had mainly been considered a tissue with the function of nonshivering thermogenesis, maintaining body ...temperature in key organs in newborns who have high body surface areas relative to their weight and thus marked radiative heat loss. BAT was believed to have substantially disappeared by adulthood. Molecular imaging with
F-FDG PET and PET combined with CT, as well as imaging with
I-metaiodobenzylguanidine (MIBG) beginning late last century have shown BAT to be present and active well into adulthood. This review highlights key aspects of BAT biology, early empiric observations misidentifying BAT, pitfalls in image interpretation, and methods to intentionally reduce BAT uptake, and outlines multiple imaging methods used to identify BAT in vivo. The therapeutic potential of increasing the amount or activity of BAT for weight loss and improvement of glucose and lipid profiles is highlighted as a major opportunity. Molecular imaging can help dissect the physiology of this complex dynamic tissue and offers the potential for addressing challenges separating "active BAT" from "total BAT." Research in BAT has grown extensively, and
F-FDG PET is the key imaging procedure against which all other BAT imaging methods must be compared. Given the multiple functions of BAT, it is reasonable to consider it a previously unrecognized endocrine tissue and thus an appropriate topic for review in this supplement to
•Outbreaks of multi-drug resistant (MDR) Shigella are on the rise among men who have sex with men (MSM).•Using whole-genome sequencing, we identified a novel MDR Shigella flexneri strain.•This novel ...strain was found in an MSM patient without a travel history.•Genomic characterization helps monitor the spread of MDR Shigella among MSM.
Clustered outbreaks of multi-drug resistant (MDR) Shigella are on the rise among men who have sex with men (MSM). Identification of MDR sub-lineages is critical for clinical management and public health interventions. Here, we describe a novel MDR sub-lineage of Shigella flexneri isolated from an MSM patient without a travel history in Southern California. Detailed genomic characterization of this novel strain would serve as a reference to aid monitoring and future outbreak investigation of MDR Shigella among MSM.
Serratia marcescens is an environmental gram-negative bacterium that causes invasive disease in rare cases. During 2020-2022, an outbreak of 21 invasive Serratia infections occurred in a prison in ...California, USA. Most (95%) patients had a history of recent injection drug use (IDU). We performed whole-genome sequencing and found isolates from 8 patients and 2 pieces of IDU equipment were closely related. We also identified social interactions among patients. We recovered S. marcescens from multiple environmental samples throughout the prison, including personal containers storing Cell Block 64 (CB64), a quaternary ammonium disinfectant solution. CB64 preparation and storage conditions were suboptimal for S. marcescens disinfection. The outbreak was likely caused by contaminated CB64 and propagated by shared IDU equipment and social connections. Ensuring appropriate preparation, storage, and availability of disinfectants and enacting interventions to counteract disease spread through IDU can reduce risks for invasive Serratia infections in California prisons.
Knowledge of the intrinsic variability of radiomic features is essential to the proper interpretation of changes in these features over time. The primary aim of this study was to assess the ...test-retest repeatability of radiomic features extracted from
F-FDG PET images of cervical tumors. The impact of different image preprocessing methods was also explored.
Patients with cervical cancer underwent baseline and repeat
F-FDG PET/CT imaging within 7 d. PET images were reconstructed using 2 methods: ordered-subset expectation maximization (PET
) or ordered-subset expectation maximization with point-spread function (PET
). Tumors were segmented to produce whole-tumor volumes of interest (VOI
) and 40% isocontours (VOI
). Voxels were either left at the default size or resampled to 3-mm isotropic voxels. SUV was discretized to a fixed number of bins (32, 64, or 128). Radiomic features were extracted from both VOIs, and repeatability was then assessed using the Lin concordance correlation coefficient (CCC).
Eleven patients were enrolled and completed the test-retest PET/CT imaging protocol. Shape, neighborhood gray-level difference matrix, and gray-level cooccurrence matrix features were repeatable, with a mean CCC value of 0.81. Radiomic features extracted from PET
images showed significantly better repeatability than features extracted from PET
images (
< 0.001). Radiomic features extracted from VOI
were more repeatable than features extracted from VOI
(
< 0.001). For most features (78.4%), a change in bin number or voxel size resulted in less than a 10% change in feature value. All gray-level emphasis and gray-level run emphasis features showed poor repeatability (CCC values < 0.52) when extracted from VOI
but were highly repeatable (mean CCC values > 0.96) when extracted from VOI
Shape, gray-level cooccurrence matrix, and neighborhood gray-level difference matrix radiomic features were consistently repeatable, whereas gray-level run length matrix and gray-level zone length matrix features were highly variable. Radiomic features extracted from VOI
were more repeatable than features extracted from VOI
Changes in voxel size or SUV discretization parameters typically resulted in relatively small differences in feature value, though several features were highly sensitive to these changes.
Clonal bacterial cells can give rise to functionally heterogeneous subpopulations. This diversification is considered an adaptation strategy that has been demonstrated for several bacterial species, ...including Salmonella enterica serovar Typhimurium. In previous studies on mouse models infected orally with pure Salmonella cultures, derived bacterial cells collected from animal tissues were found to express heterogenous phenotypes. Here, we show mixed Salmonella populations, apparently derived from the same progenitor, present in human specimens collected at a single disease time point, and in a long-term-infected patient, these Salmonella were no longer expressing surface-exposed antigen epitopes by isolates collected at earlier days of the disease. The subpopulations express different phenotypes related to cell surface antigen expression, motility, biofilm formation, biochemical metabolism, and antibiotic resistance, which can all contribute to pathogenicity. Some of the phenotypes correlate with single nucleotide polymorphisms or other sequence changes in bacterial genomes. These genetic variations can alter synthesis of cell membrane-associated molecules such as lipopolysaccharides and lipoproteins, leading to changes in bacterial surface structure and function. This study demonstrates the limitation of Salmonella diagnostic methods that are based on a single-cell population which may not represent the heterogenous bacterial community in infected humans.
In animal model systems, heterogenous Salmonella phenotypes were found previously to regulate bacterial infections. We describe in this communication that different Salmonella phenotypes also exist in infected humans at a single disease time point and that their phenotypic and molecular traits are associated with different aspects of pathogenicity. Notably, variation in genes encoding antibiotic resistance and two-component systems were observed from the subpopulations of a patient suffering from persistent salmonellosis. Therefore, clinical and public health interventions of the disease that are based on diagnosis of a single-cell population may miss other subpopulations that can cause residual human infections.
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