The elevation of Abeta42 plasma levels in women with MCI may represent a biologic explanation for the sex-dependent increased incidence of late-onset AD in women identified by epidemiologic studies.

BackgroundEffective anticancer therapy is thought to involve induction of tumour cell death through apoptosis and/or necrosis. [18F]ICMT-11, an isatin sulfonamide caspase-3/7-specific radiotracer, has been developed for PET imaging and shown to have favourable dosimetry, safety, and biodistribution. We report the translation of [18F]ICMT-11 PET to measure chemotherapy-induced caspase-3/7 activation in breast and lung cancer patients receiving first-line therapy.ResultsBreast tumour SUVmax of [18F]ICMT-11 was low at baseline and unchanged following therapy. Measurement of M30/M60 cytokeratin-18 cleavage products showed that therapy was predominantly not apoptosis in nature. While increases in caspase-3 staining on breast histology were seen, post-treatment caspase-3 positivity values were only approximately 1%; this low level of caspase-3 could have limited sensitive detection by [18F]ICMT-11-PET. Fourteen out of 15 breast cancer patients responded to first–line chemotherapy (complete or partial response); one patient had stable disease. Four patients showed increases in regions of high tumour [18F]ICMT-11 intensity on voxel-wise analysis of tumour data (classed as PADS); response was not exclusive to patients with this phenotype. In patients with lung cancer, multi-parametric [18F]ICMT-11 PET and MRI (diffusion-weighted- and dynamic contrast enhanced-MRI) showed that PET changes were concordant with cell death in the absence of significant perfusion changes.ConclusionThis study highlights the potential use of [18F]ICMT-11 PET as a promising candidate for non-invasive imaging of caspase3/7 activation, and the difficulties encountered in assessing early-treatment responses. We summarize that tumour response could occur in the absence of predominant chemotherapy-induced caspase-3/7 activation measured non-invasively across entire tumour lesions in patients with breast and lung cancer.Electronic supplementary materialThe online version of this article (10.1007/s00259-018-4098-9) contains supplementary material, which is available to authorized users.

Sourdough bakery products could promote better postprandial gastrointestinal function in healthy adults and be more acceptable than those prepared with brewer's yeast. This trial was registered at www.clinicaltrials.gov as NCT03207516.

Using multivariate analysis of both PET and MRI parameters, a prognostic model including Ktrans and SUV was able to predict the tumour subtype in 38 of 49 patients (77.6%, p < 0.001), with higher accuracy for the luminal B subtype (86.2%).

CTCA has led to a non-invasive estimation of CAAs prevalence and characterization of aneurysmal features and coronary anatomy. Overcoming ICA limitations, CTCA has provided a fine analysis of the aneurysms, also in presence of intraluminal thrombi.

Purpose : The spatio-molecular distribution of choline and its metabolites in tumors is highly heterogeneous. Due to regulation of choline metabolism by hypoxic transcriptional signaling and other survival factors, we envisage that detection of such heterogeneity in patient tumors could provide the basis for advanced localized therapy. However, non-invasive methods to assess this phenomenon in patients are limited. We investigated such heterogeneity in Non-Small Cell Lung Cancer (NSCLC) with [ 18 F]fluoromethyl-(1,2- 2 H 4 ) choline ([ 18 F]D4-FCH) and positron emission tomography/computed tomography (PET/CT). Experimental design : [ 18 F]D4-FCH (300.5±72.9MBq [147.60-363.6MBq]) was administered intravenously to 17 newly diagnosed NSCLC patients. PET/CT scans were acquired concurrently with radioactive blood sampling to permit mathematical modelling of blood-tissue transcellular rate constants. Comparisons were made with biopsy-derived choline kinase-α (CHKα) expression and diagnostic [ 18 F]fluorodeoxyglucose ([ 18 F]FDG) scans. Results : Oxidation of [ 18 F]D4-FCH to [ 18 F]D4-fluorobetaine was suppressed (48.58±0.31% parent at 60 min) likely due to the deuterium isotope effect embodied within the design of the radiotracer. Early (5 min) and late (60 min) images showed specific uptake of tracer in all 51 lesions (tumors, lymph nodes and metastases) from 17 patients analyzed. [ 18 F]D4-FCH-derived uptake (SUV 60max ) in index primary lesions (n=17) ranged between 2.87-10.13; lower than that of [ 18 F]FDG PET [6.89-22.64]. Mathematical modelling demonstrated net irreversible uptake of [ 18 F]D4-FCH at steady-state, and parametric mapping of the entire tumor showed large intratumorally heterogeneity in radiotracer retention, which is likely to have influenced correlations with biopsy-derived CHKα expression. Conclusions : [ 18 F]D4-FCH is detectable in NSCLC with large intratumorally heterogeneity, which could be exploited in the future for targeting localized therapy.

Background Alzheimer’s disease, the most common cause of dementia, causes a progressive and irreversible deterioration of cognition that can sometimes be difficult to diagnose, leading to suboptimal patient care. Methods We developed a predictive model that computes multi-regional statistical morpho-functional mesoscopic traits from T1-weighted MRI scans, with or without cognitive scores. For each patient, a biomarker called “Alzheimer’s Predictive Vector” (ApV) was derived using a two-stage least absolute shrinkage and selection operator (LASSO). Results The ApV reliably discriminates between people with (ADrp) and without (nADrp) Alzheimer’s related pathologies (98% and 81% accuracy between ADrp - including the early form, mild cognitive impairment - and nADrp in internal and external hold-out test sets, respectively), without any a priori assumptions or need for neuroradiology reads. The new test is superior to standard hippocampal atrophy (26% accuracy) and cerebrospinal fluid beta amyloid measure (62% accuracy). A multiparametric analysis compared DTI-MRI derived fractional anisotropy, whose readout of neuronal loss agrees with ADrp phenotype, and SNPrs2075650 is significantly altered in patients with ADrp-like phenotype. Conclusions This new data analytic method demonstrates potential for increasing accuracy of Alzheimer diagnosis.

PurposeThe purpose of this study is to investigate the robustness of pharmacokinetic modelling of DCE-MRI brain tumour data and to ascertain reliable perfusion parameters through a model selection process and a stability test.MethodsDCE-MRI data of 14 patients with primary brain tumours were analysed using the Tofts model (TM), the extended Tofts model (ETM), the shutter speed model (SSM) and the extended shutter speed model (ESSM). A no-effect model (NEM) was implemented to assess overfitting of data by the other models. For each lesion, the Akaike Information Criteria (AIC) was used to build a 3D model selection map. The variability of each pharmacokinetic parameter extracted from this map was assessed with a noise propagation procedure, resulting in voxel-wise distributions of the coefficient of variation (CV).ResultsThe model selection map over all patients showed NEM had the best fit in 35.5% of voxels, followed by ETM (32%), TM (28.2%), SSM (4.3%) and ESSM (< 0.1%). In analysing the reliability of Ktrans, when considering regions with a CV < 20%, ≈ 25% of voxels were found to be stable across all patients. The remaining 75% of voxels were considered unreliable.ConclusionsThe majority of studies quantifying DCE-MRI data in brain tumours only consider a single model and whole tumour statistics for the output parameters. Appropriate model selection, considering tissue biology and its effects on blood brain barrier permeability and exchange conditions, together with an analysis on the reliability and stability of the calculated parameters, is critical in processing robust brain tumour DCE-MRI data.