The development of integrated positron emission tomography (PET)/magnetic resonance imaging (MRI) scanners opened a new scenario for cancer diagnosis, treatment, and follow-up. Multimodal imaging combines functional and morphological information from different modalities, which, singularly, cannot provide a comprehensive pathophysiological overview. Molecular imaging exploits multimodal imaging in order to obtain information at a biological and cellular level; in this way, it is possible to track biological pathways and discover many typical tumoral features. In this context, nanoparticle-based contrast agents (CAs) can improve probe biocompatibility and biodistribution, prolonging blood half-life to achieve specific target accumulation and non-toxicity. In addition, CAs can be simultaneously delivered with drugs or, in general, therapeutic agents gathering a dual diagnostic and therapeutic effect in order to perform cancer diagnosis and treatment simultaneous. The way for personalized medicine is not so far. Herein, we report principles, characteristics, applications, and concerns of nanoparticle (NP)-based PET/MRI CAs. modality allows gathering all the necessary morphological and functional information, the combination of two or more imaging techniques, also called multimodal imaging or hybrid imaging, can offer synergistic advantages over any modality alone [11], overcoming its drawbacks and strengthening the peculiarities. The traditional approach was directed to the integration of a structural imaging modality (CT, MRI) with a functional highly sensitive imaging modality (PET/SPECT). Thus, firstly, PET/CT and SPECT/CT were introduced in clinical settings. The first PET/CT scanner was developed in 1998 by Townsend and colleagues [12] and was commercialized in 2001. It consists of a PET component independent from CT, and a single bed moves axially into the scanner while the patient sequentially performs CT and PET scans [13]. To date, PET/CT scanners completely replaced standalone PET scanners [14], exploiting anatomical reference and attenuation estimation from CT data. The success of PET/CT scanners inspired the feasibility of a PET/MRI scanner [15]. Three different configuration options were developed over the years [16]: the first consists of a sequential acquisition, similarly to PET/CT, where the patient undergoes firstly a MRI scan and later a PET scan; even if the MRI and PET components must be minimally modified, two consecutive acquisitions are performed without simultaneity. Temporal mismatches between PET metabolic data and MRI morphological information such as patient motion are the main weak points [7]. Nearly 15 years ago, some researchers working in preclinical settings analyzed the possibility of integrating a modified PET scanner into an MRI system. In Tubingen, Germany, an MRI-compatible PET scanner was inserted into a 3T clinical MRI scanner [8]; this system is suitable for preclinical studies or human brain imaging. The third option considers a first fully integrated whole-body PET/MRI sys...

Circulating biomarkers available in clinical practice do not allow to stratify patients with coronary heart disease (CHD) prior the onset of a clinically relevant event. We evaluated the methylation status of specific genomic segments and gene expression in peripheral blood of patients undergoing Cardiac Computed Tomography (CCT) for CHD (n = 95).We choose to investigate cholesterol metabolism. Methylation and gene expression of low density lipoprotein receptor (LDLR), sterol regulatory element-binding factor 2 (SREBF2) and ATP-binding cassette transporter 1 (ABCA1) were evaluated by qRT-PCR. Calcium score (CACS), stenosis degree, total plaque volume (TPV), calcified plaque volume (CPV), non-calcified plaque volume (NCPV) and plaque burden (PB) were assessed in all CHD patients (n = 65). The percentage of methylation at the specific analyzed segment of LDLR promoter was higher in CHD patients vs healthy subjects (HS) (n = 30) (p = 0.001). LDLR, SREBF2 and ABCA1 mRNAs were up-regulated in CHD patients vs HS (p = 0.02; p = 0.019; p = 0.008). SREBF2 was overexpressed in patients with coronary stenosis ≥50% vs subjects with stenosis <50% (p = 0.036). After adjustment for risk factors and clinical features, ABCA1 (p = 0.005) and SREBF2 (p = 0.010) gene expression were identified as independent predictors of CHD and severity. ROC curve analysis revealed a good performance of ABCA1 on predicting CHD (AUC = 0.768; p<0.001) and of SREBF2 for the prediction of disease severity (AUC = 0.815; p<0.001). Moreover, adjusted multivariate analysis demonstrated SREBF2 as independent predictor of CPV, NCPV and TPV (p = 0.022; p = 0.002 and p = 0.006) and ABCA1 as independent predictor of NCPV and TPV (p = 0.002 and p = 0.013).CHD presence and characteristics are related to selected circulating transcriptional and epigenetic-sensitive biomarkers linked to cholesterol pathway. More extensive analysis of CHD phenotypes and circulating biomarkers might improve and personalize cardiovascular risk stratification in the clinical settings.

Hydrodenticity explains the boosting (12-times) of the Gd-DTPA relaxivity by tuning hydrogel structural parameters, potentially enabling the reduction of the administration dosage as approved for clinical use. [Formula: see text].