All women undergo the menopause transition (MT), a neuro-endocrinological process that impacts aging trajectories of multiple organ systems including brain. The MT occurs over time and is ...characterized by clinically defined stages with specific neurological symptoms. Yet, little is known of how this process impacts the human brain. This multi-modality neuroimaging study indicates substantial differences in brain structure, connectivity, and energy metabolism across MT stages (pre-menopause, peri-menopause, and post-menopause). These effects involved brain regions subserving higher-order cognitive processes and were specific to menopausal endocrine aging rather than chronological aging, as determined by comparison to age-matched males. Brain biomarkers largely stabilized post-menopause, and gray matter volume (GMV) recovered in key brain regions for cognitive aging. Notably, GMV recovery and in vivo brain mitochondria ATP production correlated with preservation of cognitive performance post-menopause, suggesting adaptive compensatory processes. In parallel to the adaptive process, amyloid-β deposition was more pronounced in peri-menopausal and post-menopausal women carrying apolipoprotein E-4 (APOE-4) genotype, the major genetic risk factor for late-onset Alzheimer's disease, relative to genotype-matched males. These data show that human menopause is a dynamic neurological transition that significantly impacts brain structure, connectivity, and metabolic profile during midlife endocrine aging of the female brain.
Neuroendocrine neoplasms (NENs) are heterogeneous tumours with a common phenotype descended from the diffuse endocrine system. NENs are found nearly anywhere in the body but the most frequent ...location is the gastrointestinal tract. Gastrointestinal neuroendocrine neoplasms (GI-NENs) are rather uncommon, representing around 2% of all gastrointestinal tumours and 20–30% of all primary neoplasms of the small bowel. GI-NENs have various clinical manifestations due to the different substances they can produce; some of these tumours appear to be associated with familial syndromes, such as multiple endocrine neoplasm and neurofibromatosis type 1. The current WHO classification (2019) divides NENs into three major categories: well-differentiated NENs, poorly differentiated NENs, and mixed neuroendocrine-non-neuroendocrine neoplasms. The diagnosis, localization, and staging of GI-NENs include morphology and functional imaging, above all contrast-enhanced computed tomography (CECT), and in the field of nuclear medicine imaging, a key role is played by
68
Ga-labelled-somatostatin analogues (
68
Ga-DOTA-peptides) positron emission tomography/computed tomography (PET/TC). In this review of recent literature, we described the objectives of morphological/functional imaging and potential future possibilities of prognostic imaging in the assessment of GI-NENs.
Purpose
An appropriate healthy control dataset is mandatory to achieve good performance in voxel-wise analyses. We aimed at evaluating 18FFDG PET brain datasets of healthy controls (HC), based on ...publicly available data, for the extraction of voxel-based brain metabolism maps at the single-subject level.
Methods
Selection of HC images was based on visual rating, after Cook’s distance and jack-knife analyses, to exclude artefacts and/or outliers. The performance of these HC datasets (ADNI-HC and AIMN-HC) to extract hypometabolism patterns in single patients was tested in comparison with the standard reference HC dataset (HSR-HC) by means of Dice score analysis. We evaluated the performance and comparability of the different HC datasets in the assessment of single-subject SPM-based hypometabolism in three independent cohorts of patients, namely, ADD, bvFTD and DLB.
Results
Two-step Cook’s distance analysis and the subsequent jack-knife analysis resulted in the selection of
n
= 125 subjects from the AIMN-HC dataset and
n
= 75 subjects from the ADNI-HC dataset. The average concordance between SPM hypometabolism t-maps in the three patient cohorts, as obtained with the new datasets and compared to the HSR-HC standard reference dataset, was 0.87 for the AIMN-HC dataset and 0.83 for the ADNI-HC dataset. Pattern expression analysis revealed high overall accuracy (> 80%) of the SPM t-map classification according to different statistical thresholds and sample sizes.
Conclusions
The applied procedures ensure validity of these HC datasets for the single-subject estimation of brain metabolism using voxel-wise comparisons. These well-selected HC datasets are ready-to-use in research and clinical settings.
After advanced age, female sex is the major risk factor for Alzheimer's disease (AD). The biological mechanisms underlying the increased AD risk in women remain largely undetermined. Preclinical ...studies identified the perimenopause to menopause transition, a neuroendocrine transition state unique to the female, as a sex-specific risk factor for AD. In animals, estrogenic regulation of cerebral glucose metabolism (CMRglc) falters during perimenopause. This is evident in glucose hypometabolism and decline in mitochondrial efficiency which is sustained thereafter. This study bridges basic to clinical science to characterize brain bioenergetics in a cohort of forty-three, 40-60 year-old clinically and cognitively normal women at different endocrine transition stages including premenopause (controls, CNT, n = 15), perimenopause (PERI, n = 14) and postmenopause (MENO, n = 14). All participants received clinical, laboratory and neuropsychological examinations, 18F-fluoro-deoxyglucose (FDG)-Positron Emission Tomography (PET) FDG-PET scans to estimate CMRglc, and platelet mitochondrial cytochrome oxidase (COX) activity measures. Statistical parametric mapping and multiple regression models were used to examine clinical, CMRglc and COX data across groups. As expected, the MENO group was older than PERI and controls. Groups were otherwise comparable for clinical measures and distribution of APOE4 genotype. Both MENO and PERI groups exhibited reduced CMRglc in AD-vulnerable regions which was correlated with decline in mitochondrial COX activity compared to CNT (p's<0.001). A gradient in biomarker abnormalities was most pronounced in MENO, intermediate in PERI, and lowest in CNT (p<0.001). Biomarkers correlated with immediate and delayed memory scores (Pearson's 0.26≤r≤0.32, p≤0.05). These findings validate earlier preclinical findings and indicate emergence of bioenergetic deficits in perimenopausal and postmenopausal women, suggesting that the optimal window of opportunity for therapeutic intervention in women is early in the endocrine aging process.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Chimeric antigen receptor–engineered (CAR) T cells are emerging powerful therapies for patients with refractory/relapsed B-cell lymphomas. 18FFDG PET/CT plays a key role during staging and response ...assessment in patients with lymphoma; however, the evidence about its utility in CAR-T therapies for lymphomas is limited. This review article aims to provide an overview of the role of PET/CT during CAR-T cell therapy in B-cell lymphomas, focusing on the prognostic value of metabolic parameters, as well as on response assessment. Data from the literature report on the use of 18FFDG PET/CT at the baseline with two scans performed before treatment started focused on the time of decision (TD) PET/CT and time of transfusion (TT) PET/CT. Metabolic tumor burden is the most studied parameter associated with disease progression and overall survival, making us able to predict the occurrence of adverse effects. Instead, for post-therapy evaluation, 1 month (M1) PET/CT seems the preferable time slot for response assessment and in this setting, the Deauville 5-point scale (DS), volumetric analyses, SUVmax, and its variation between different time points (∆SUVmax) have been evaluated, confirming the usefulness of M1 PET/CT, especially in the case of pseudoprogression. Additionally, an emerging role of PET/CT brain scans is reported for the evaluation of neurotoxicity related to CAR-T therapies. Overall, PET/CT results to be an accurate method in all phases of CAR-T treatment, with particular interest in assessing treatment response. Moreover, PET parameters have been reported to be reliable predictors of outcome and severe toxicity.
Background and purpose
Morphologic magnetic resonance imaging (MRI) for characterization of salivary gland tumors has limited utility, and the use of perfusion MRI data in the clinical setting is ...controversial. We examined the potential of tissue-normalized dynamic contrast-enhanced (DCE) MRI pharmacokinetic parameters of salivary gland tumors as imaging biomarkers for characterization and differentiation between benign and malignant lesions.
Materials and methods
DCE-MR images acquired from 60 patients with parotid and submandibular gland tumors were retrospectively reviewed. Pharmacokinetic parameters as transfer constant (
Ktrans)
, rate constant (
Kep)
, extracellular space volume
(Ve)
, fractional plasma volume (
Vp),
and
AEC
(area of all times enhancement curve) were measured on both the lesion and the normal contralateral salivary gland parenchyma. Lesion/parenchyma ratio (L/P) for each parameter was calculated.
Results
Five groups of lesions were identified (reference: histopathology): pleomorphic adenomas(
n
= 20), Warthin tumors(
n
= 16), other benign entities(
n
= 4), non-Hodgkin lymphomas(
n
= 4), and malignancies(
n
= 16). Significant differences were seen for mean values of L/P
Ktrans
(higher in malignancies), L/P
Kep
(lower in adenomas than Warthin tumors), L/P
Ve
(lower in Warthin tumors and lymphomas), L/P
Vp
(higher in Warthin tumors and malignancies than adenomas), and L/P
AEC
(higher in malignancies). Significant differences were found between benign and malignant (non-lymphoproliferative) lesions in mean value of L/P
Ktrans
(0.485 and 1.581), L/P
Vp
(1.288 and 2.834), and L/P
AEC
(0.682 and 1.910). ROC analysis demonstrated the highest AUC (0.96) for L/P
AEC
, with sensitivity and specificity for malignancy of 93.8% and 97.5% (cutoff value = 1.038).
Conclusion
Lesion/parenchyma ratio of DCE-MRI pharmacokinetic data could be helpful for recognizing the principal types of salivary gland tumors; L/P
AEC
seems a valuable biomarker for differentiating benign from malignant tumors.
Receptor tyrosine kinases, or RTKs, are one large family of cell surface receptors involved in signal transduction, which represent an integral part of the signaling pathways. They play a crucial ...role in most important cellular processes, starting with the cell cycle, proliferation and differentiation, as well as cell migration, metabolism and survival. The introduction of ImmunoPET evaluating the expression of RTKs by specific monoclonal antibodies (mAbs) or antibody fragments is regarded as a promising tool for imaging treatment efficacy and developing anticancer therapeutics. Our review focuses mainly on the current clinical research regarding ImmunoPET targeting RTKs, with particular interest in the epidermal growth factor family, or HER family, and vascular endothelial-derived growth factor/receptor.
The aim of this study is to find a correlation between tumoral heterogeneity of squamous cell carcinoma of the oropharynx and human papillomavirus (HPV) status and to determine whether analysis of ...texture features of primary lesion on contrast-enhanced CT (CECT) images can be useful in predicting the HPV positivity. Fifty patients with diagnosis of oropharyngeal carcinoma and pre-treatment CECT were included; tumoral heterogeneity of each lesion was evaluated by extracting quantitative texture parameters of first and higher orders.
T
test and logistic regression were conducted to evaluate the effects of different textural characteristics. There were 35 HPV+ and 15 HPV− lesions. Statistically significant (
p
< 0.05) differences were seen in multiple higher-order extracted parameters. The logistic regression model correctly classified lesions with an accuracy of 95.2%. CT texture analysis of primary oropharyngeal cancer may be used as a tool for predicting the HPV status.
Objective
This study was performed to evaluate the prognostic meaning of volumetric and semi-quantitative parameters measured using 18FFDG PET/CT and somatostatin receptor (SSTR) imaging in patients ...with typical lung carcinoid (TC), and their relationship with proliferative index (Ki67).
Methods
We retrospectively reviewed 67 patients (38–94 years old, mean: 69.7) with diagnosis of TC who underwent 18FFDG PET/CT and/or SSTR scintigraphy/SPECT with 111InDTPA-Octreotide plus contrast-enhanced CT (CECT) at staging evaluation. All patients had Ki67 measured and a follow-up (FU) of at least 1 year. SSTR density (SSTRd) was calculated as the percentage difference of tumor/non-tumor ratio at 4 and 24 h post-injection. At PET/CT, metabolic activity was measured using SUVmax and SUVratio; volumetric parameters included MTV and TLG of the primary tumor, measured using the threshold SUV41%. ROC analysis, discriminant analysis and Kaplan–Meier curves (KM) were performed.
Results
11 patients died during FU. Disease stage (localized versus advanced), SUVratio, SUVmax, Ki67, MTV and TLG were significantly higher in non-survivors than in survivors. ROC curves resulted statistically significant for Ki67, SUVratio, SUVmax, MTV and TLG. On multivariate analysis, stage of disease and TLG were significant independent predictors of overall survival (OS). In KM curves, the combination of disease stage and TLG identified four groups with significantly different outcomes (
p
< 0.005). Metabolic activity (SUVmax and SUVratio) was confirmed as significant independent prognostic factor for OS also in patients with advanced disease, with the best AUC using SUVmax.
In patients with advanced and localized disease, SSTRd proved to be the best imaging prognostic factor for progression and for disease-free survival (DFS), respectively. In localized disease, SSTRd 31.5% identified two subgroups of patients with significant different DFS distribution and in advanced disease, a high cutoff value (58.5%) was a significant predictor of adverse prognosis.
Conclusion
Volumetric and semi-quantitative parameters measured using 18FFDG PET/CT and SSTR imaging combined with Ki67 may provide a reference for prognosis evaluation of patients with TC, to better stratify risk groups with the goal of developing individualized therapeutic strategies.
In the last decade, monoclonal antibodies (mAbs) targeting CTLA-4, PD-1, or PD-L1 have been developed and immune checkpoint inhibitors (ICIs) have become the main approach in cancer immunotherapy. ...However, not all patients benefit from ICI therapy and some are at risk of developing treatment-induced side-effects. These aspects, in parallel with the imaging challenges related to response assessments during immunotherapy, have driven scientific research to the discovery of new predictive biomarkers to individualize patients who could benefit from ICIs. In this context, molecular imaging using PET (positron emission tomography), which allows for whole-body tumor visualization, may be a promising non-invasive method for the determination of patients' sensitivity to antibody drugs. Several PET tracers, diverse from 2-
FFDG (or 2-Deoxy-2-
Ffluoroglucose), have been developed to image immune checkpoints (ICs) or key elements of the immune system, although most of them are still in preclinical phases. Herein, we present the current state of the ImmunoPET-targeting of IC proteins with mAbs and antibody fragments, with a main focus on the latest developments in clinical molecular imaging studies of solid tumors. Moreover, given the relevance of the immune system and of tumor-infiltrating lymphocytes in particular in the prediction of the benefit of ICIs, we dedicate a portion of this review to ImmunoPET-targeting T cells.
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