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Brain : a Journal of Neurology Jun 2024Increasing evidence shows that neuroinflammation is a possible modulator of tau spread effects on cognitive impairment in Alzheimer's disease. In this context, plasma...
Increasing evidence shows that neuroinflammation is a possible modulator of tau spread effects on cognitive impairment in Alzheimer's disease. In this context, plasma levels of the glial fibrillary acidic protein (GFAP) have been suggested to have a robust association with Alzheimer's disease pathophysiology. This study aims to assess the correlation between plasma GFAP and Alzheimer's disease pathology, and their synergistic effect on cognitive performance and decline. A cohort of 122 memory clinic subjects with amyloid and tau positron emission tomography, MRI scans, plasma GFAP, and Mini-Mental State Examination (MMSE) was included in the study. A subsample of 94 subjects had a follow-up MMSE score at least one year after baseline. Regional and voxel-based correlations between Alzheimer's disease biomarkers and plasma GFAP were assessed. Mediation analyses were performed to evaluate the effects of plasma GFAP on the association between amyloid and tau PET, and tau PET and cognitive impairment and decline. GFAP was associated with increased tau PET ligand uptake in the lateral temporal and inferior temporal lobes in a strong left-sided pattern independently of age, gender, education, amyloid, and APOE status (β=0.001, p < 0.01). The annual rate of MMSE change was significantly and independently correlated with both GFAP (β=0.006, p < 0.01) and global tau SUVR (β=4.33, p < 0.01), but not with amyloid burden. Partial mediation effects of GFAP were found on the association between amyloid and tau pathology (13.7%), and between tau pathology and cognitive decline (17.4%), but not on global cognition at baseline. Neuroinflammation measured by circulating GFAP is independently associated with tau Alzheimer's disease pathology and with cognitive decline, suggesting neuroinflammation as a potential target for future disease-modifying trials targeting tau pathology. Peretti et al. show that a circulatory marker of neuroinflammation-glial fibrillary acidic protein-is associated with tau pathology in lateral temporal and frontal regions in patients with Alzheimer's disease, independent of amyloid load. Neuroinflammation appears to modulate the association between amyloid and tau biomarkers.
PubMed: 38940331
DOI: 10.1093/brain/awae211 -
Journal of Extracellular Biology Feb 2024Extracellular vesicles (EVs) have been involved in metabolic syndrome, although their specific role in the development of the pathology is still unknown. To further...
Extracellular vesicles (EVs) have been involved in metabolic syndrome, although their specific role in the development of the pathology is still unknown. To further study the role of EVs, we have analysed by Raman tweezers microspectroscopy and mass spectrometry-based lipidomics the small EVs population secreted by fatty (ZF) and lean (ZL) hepatocytes obtained from Zucker rats. We have also explored in vivo and ex vivo biodistribution of these EVs through fluorine-18-radiolabelling using a positron emission tomography imaging. Based on the proportion of proteins to lipids and the types of lipids, our results indicate that within the range of small EVs, primary hepatocytes secrete different subpopulations of particles. These differences were observed in the enrichment of triglyceride species in EVs secreted by ZF hepatocytes. Biodistribution experiments showed accumulation in the brain, heart, lungs, kidney and specially in bladder after intravenous administration. In summary, we show that EVs released by a fatty hepatocytes carry a different lipid signature compared to their lean counterpart. Biodistribution experiment has shown no difference in the distribution of EVs secreted by ZF and ZL hepatocytes but has given us a first view of possible target organs for these particles. Our results might open a door to both pathology studies and therapeutic interventions.
PubMed: 38939902
DOI: 10.1002/jex2.140 -
JACC. Advances May 2024It is not known whether the transition from obesity and severe obesity, as 2 different metabolic disease entities, affect flow-mediated and, thus, endothelium-dependent...
BACKGROUND
It is not known whether the transition from obesity and severe obesity, as 2 different metabolic disease entities, affect flow-mediated and, thus, endothelium-dependent epicardial vasodilation.
OBJECTIVES
The purpose of this study was to investigate the effect of obesity and severe obesity on flow-mediated epicardial vasomotion with positron emission tomography/computed tomography-determined longitudinal decrease in myocardial blood flow (MBF) from the base-to-apex direction of the left ventricle or gradient.
METHODS
N-ammonia positron emission tomography/computed tomography evaluated global MBF during pharmacologically induced hyperemia and at rest for assessment of coronary microvascular function. In addition, the Δ longitudinal MBF gradient (hyperemia minus rest) was determined. Patients were then grouped according to the body mass index (BMI) into normal weight (NW) (BMI 20.0-24.9 kg/m, n = 27), overweight (OW) (BMI 25.0-29.9 kg/m, n = 29), obesity (OB) (BMI 30.0-39.9 kg/m, n = 53), and severe obesity (morbid obesity: BMI ≥40 kg/m, n = 43).
RESULTS
Compared to NW, left ventricular Δ longitudinal MBF gradient progressively declined in OW and OB (0.04 ± 0.09 mL/g/min vs -0.11 ± 0.14 mL/g/min and -0.15 ± 0.11 mL/g/min; ≤ 0.001, respectively) but not significantly in SOB (-0.01 ± 0.11 mL/g/min, = 0.066). Regadenoson-induced global hyperemic MBF was lower in OB than in NW (1.88 ± 0.40 mL/g/min vs 2.35 ± 0.32 mL/g/min; ≤ 0.001), while comparable between NW and SOB (2.35 ± 0.32 mL/g/min vs 2.26 ± 0.40 mL/g/min; = 0.302). The BMI of the study population was associated with the Δ longitudinal MBF gradient in a U-turn fashion (r = 0.362, standard error of the estimate = 0.124; < 0.001).
CONCLUSIONS
Increased body weight associates with abnormalities in coronary circulatory function that advances from an impairment flow-mediated, epicardial vasodilation in overweight and obesity to coronary microvascular dysfunction in obesity, not observed in severe obesity. The U-turn of flow-mediated epicardial vasomotion outlines obesity and severe obesity to affect epicardial endothelial function differently.
PubMed: 38939628
DOI: 10.1016/j.jacadv.2024.100936 -
Polish Journal of Radiology 2024To evaluate the predictive capability of the apparent diffusion coefficient (ADC) at initial diagnosis in treatment-naive patients with laryngeal squamous cell carcinoma...
PURPOSE
To evaluate the predictive capability of the apparent diffusion coefficient (ADC) at initial diagnosis in treatment-naive patients with laryngeal squamous cell carcinoma (LSCC) for the development of future metastases.
MATERIAL AND METHODS
Magnetic resonance images of patients with pathologically proven non-metastatic, treatmentnaive LSCC were retrospectively evaluated. Follow-up positron emission tomography scans were assessed for the scanning of metastases.
RESULTS
A total of 37 patients (32 males and 5 females) with a mean age of 62.8 ± 8.9 years were enrolled. Mean tumour volume and ADC were 4.8 ± 62 cm and 0.72 ± 0.51 × 10 mm/s, respectively. Six local and 8 distant metastases were detected in a mean follow-up period of 17.5 ± 10.2 months. A significant association between ADC and the presence distant metastases ( = 0.046) and local metastases ( = 0.042) was found. The difference in mean ADC values between future metastatic and non-metastatic initial tumours was significant ( = 0.017).
CONCLUSIONS
Pre-treatment ADC values and volume of the initial tumour might provide early information about the development of future metastases in patients with LSCC in this series.
PubMed: 38938659
DOI: 10.5114/pjr/187675 -
Frontiers in Medicine 2024Rosai-Dorfman disease (RDD) is an uncommon histiocytic disorder that occurs in nodal and/or extranodal sites. Extranodal RDD exhibits a wide range of clinical and...
Rosai-Dorfman disease (RDD) is an uncommon histiocytic disorder that occurs in nodal and/or extranodal sites. Extranodal RDD exhibits a wide range of clinical and radiological presentations, frequently leading to misdiagnoses. Involvement of the gastrointestinal (GI) system is uncommon, accounting for less than 1% of the reported cases. Here we present a case of a 54-year-old male who complained of abdominal distention and was diagnosed with RDD affecting the sigmoid colon, manifesting as a sigmoid mass. The patient had a past medical history of liver transplantation due to hepatocellular carcinoma (HC). This report details the multiphase contrast-enhanced computed tomography (CT) and fluorodeoxyglucose (F-FDG) positron emission tomography (PET-CT) imaging findings of RDD involving the sigmoid colon without lymphadenopathy, and a review of the relevant literature is provided.
PubMed: 38938381
DOI: 10.3389/fmed.2024.1425112 -
Cancer Research and Treatment Jun 2024To develop an MRI-based radiomics model to predict high-risk pathologic features for lung adenocarcinoma: micropapillary and solid pattern (MPsol), spread through air...
PURPOSE
To develop an MRI-based radiomics model to predict high-risk pathologic features for lung adenocarcinoma: micropapillary and solid pattern (MPsol), spread through air space (STAS), and poorly differentiated patterns.
MATERIALS AND METHODS
As a prospective study, we screened clinical N0 lung cancer patients who were surgical candidates and had undergone both 18F-fluorodeoxyglucose (FDG) positron emission tomography-CT (PET/CT) and chest CT from August 2018 to January 2020. We recruited patients meeting our proposed imaging criteria indicating high-risk, that is, poorer prognosis of lung adenocarcinoma, using CT and FDG PET/CT. If possible, these patients underwent an MRI examination from which we extracted 77 radiomics features from T1-contrast-enhanced and T2-weighted images. Additionally, patient demographics, SUVmax (maximum standardized uptake value) on FDG PET/CT, and the mean ADC value on DWI, were considered together to build prediction models for high-risk pathologic features.
RESULTS
Among 616 patients, 72 patients met the imaging criteria for high-risk lung cancer and underwent lung MRI. The MR-eligible group showed a higher prevalence of nodal upstaging (29.2% vs. 4.2%, p<0.001), vascular invasion (6.5% vs. 2.1%, p=0.011), high-grade pathologic features (p<0.001), worse 4-year disease free survival (p<0.001) compared with non-MR-eligible group. The prediction power for MR-based radiomics model predicting high-risk pathologic features was good, with mean area under the receiver operating curve (AUC) value measuring 0.751-0.886 in test sets. Adding clinical variables increased the predictive performance for MPsol and the poorly differentiated pattern using the 2021 grading system (AUC 0.860 and 0.907, respectively).
CONCLUSION
Our imaging criteria can effectively screen high-risk lung cancer patients and predict high-risk pathologic features by our MR-based prediction model using radiomics.
PubMed: 38938009
DOI: 10.4143/crt.2024.251 -
Scientific Data Jun 2024Accurate differentiation between angina with no obstructive coronary arteries (ANOCA) and mental stress-induced myocardial ischemia (MSIMI) is crucial for tailored...
Accurate differentiation between angina with no obstructive coronary arteries (ANOCA) and mental stress-induced myocardial ischemia (MSIMI) is crucial for tailored treatment strategies, yet public data scarcity hampers understanding. Given the higher incidence of both conditions in women, this study prospectively enrolled 80 female ANOCA and 39 age-matched female controls, subjecting them to three types of mental stress tasks. ECGs were continuously monitored across Rest, Stress, and Recover stages of the mental stress tasks, with PET/CT imaging during the Stress stage to evaluate myocardial perfusion. With PET/CT serving as the gold standard for MSIMI diagnosis, 35 of the 80 ANOCA patients were diagnosed as MSIMI. Using ECG variables from different stages of mental stress tasks, we developed five machine learning models to diagnose MSIMI. The results showed that ECG data from different stages provide valuable information for MSIMI classification. Additionally, the dataset encompassed demographic details, physiological, and blood sample test results of the patients. We anticipate this new dataset will significantly push further progress in ANOCA and MSIMI research.
Topics: Humans; Female; Myocardial Ischemia; Stress, Psychological; Electrocardiography; Machine Learning; Positron Emission Tomography Computed Tomography; Middle Aged; Angina Pectoris; Prospective Studies
PubMed: 38937514
DOI: 10.1038/s41597-024-03462-2 -
Nature Communications Jun 2024Tuberculosis remains a large global disease burden for which treatment regimens are protracted and monitoring of disease activity difficult. Existing detection methods...
Tuberculosis remains a large global disease burden for which treatment regimens are protracted and monitoring of disease activity difficult. Existing detection methods rely almost exclusively on bacterial culture from sputum which limits sampling to organisms on the pulmonary surface. Advances in monitoring tuberculous lesions have utilized the common glucoside [F]FDG, yet lack specificity to the causative pathogen Mycobacterium tuberculosis (Mtb) and so do not directly correlate with pathogen viability. Here we show that a close mimic that is also positron-emitting of the non-mammalian Mtb disaccharide trehalose - 2-[F]fluoro-2-deoxytrehalose ([F]FDT) - is a mechanism-based reporter of Mycobacteria-selective enzyme activity in vivo. Use of [F]FDT in the imaging of Mtb in diverse models of disease, including non-human primates, successfully co-opts Mtb-mediated processing of trehalose to allow the specific imaging of TB-associated lesions and to monitor the effects of treatment. A pyrogen-free, direct enzyme-catalyzed process for its radiochemical synthesis allows the ready production of [F]FDT from the most globally-abundant organic F-containing molecule, [F]FDG. The full, pre-clinical validation of both production method and [F]FDT now creates a new, bacterium-selective candidate for clinical evaluation. We anticipate that this distributable technology to generate clinical-grade [F]FDT directly from the widely-available clinical reagent [F]FDG, without need for either custom-made radioisotope generation or specialist chemical methods and/or facilities, could now usher in global, democratized access to a TB-specific PET tracer.
Topics: Animals; Mycobacterium tuberculosis; Positron-Emission Tomography; Trehalose; Tuberculosis; Humans; Mice; Fluorine Radioisotopes; Fluorodeoxyglucose F18; Radiopharmaceuticals; Disease Models, Animal; Female
PubMed: 38937448
DOI: 10.1038/s41467-024-48691-6 -
Diagnostic and Interventional Imaging Jun 2024
PubMed: 38937251
DOI: 10.1016/j.diii.2024.06.003 -
Neurobiology of Disease Jun 2024The diagnosis of amyotrophic lateral sclerosis (ALS) is primarily clinical, supported by the electromyographic examination to reveal signs of lower motor neuron damage....
BACKGROUND
The diagnosis of amyotrophic lateral sclerosis (ALS) is primarily clinical, supported by the electromyographic examination to reveal signs of lower motor neuron damage. Identifying reliable markers of upper motor neuron (UMN) involvement is challenging. On this regard, the role of transcranial magnetic stimulation-induced motor-evoked potentials (TMS-MEPs), and its relationship with UMN burden, is still under investigation.
OBJECTIVE
To evaluate the ability of TMS-MEPs in delineating the neurophysiological UMN damage, and to determine the relationship between TMS-MEPs and [F]FDG-PET measures of neural dysfunction.
METHODS
We retrospectively selected 13 ALS patients who underwent, during the diagnostic process, the TMS-MEPs and [F]FDG-PET scans. Demographic and clinical data were collected. For the MEP evaluation, we considered normal MEP, absent MEP, or significantly increased central-motor-conduction-time. For [F]FDG-PET, we conducted voxel-wise analyses, both at single-subject and group levels, exploring hypometabolism and hypermetabolism patterns in comparison with a large dataset of healthy controls (HC).
RESULTS
Based on TMS-MEPs, we identified 4/13 patients with normal MEP in all limbs (GROUP-NO), while 9/13 had an abnormal MEP in at least one limb (GROUP-AB). Despite the [F]FDG-PET single-subject analysis revealed heterogenous expression of regional hypo- and hyper-metabolism patterns in the patients, the group-level analysis revealed a common hypometabolism, involving the precentral gyrus and the supplementary motor area, the paracentral lobule and the anterior cingulate cortex in the GROUP-AB. Moreover, exclusively for the GROUP-AB compared with HC, a relative hypermetabolism was observed in the right cerebellum, right inferior and middle temporal gyrus. The GROUP-NO showed no specific cluster of hypo- and hyper-metabolism compared to HC.
CONCLUSION
This study showed altered brain metabolism only in the ALS group with abnormal MEPs, suggesting an association between the two biomarkers in defining the UMN damage.
PubMed: 38936435
DOI: 10.1016/j.nbd.2024.106579