A multi-parametric PET/MRI study of breast cancer: Evaluation of DCE-MRI pharmacokinetic models and correlation with diffusion and functional parameters.

46 patients with histologically confirmed breast cancer were enrolled and imaged with a 3T hybrid PET/MRI system, at staging. Diffusion, functional and perfusion parameters (measured by Tofts and shutter speed models) were compared. Results showed a good correlation between pharmacokinetic parameters and the SUV.

Future perspectives of nanoparticle-based contrast agents for cardiac magnetic resonance in myocardial infarction.

Cardiac Magnetic Resonance (CMR), thanks to high spatial resolution and absence of ionizing radiation, has been widely used in myocardial infarction (MI) assessment to evaluate cardiac structure, function, perfusion and viability. Nevertheless, it suffers from limitations in tissue and assessment of myocardial pathophysiological changes subsequent to MI. In this issue, nanoparticle-based contrast agents offer the possibility to track biological processes at cellular and molecular level underlying the various phases of MI, infarct healing and tissue repair. In this paper, first we examine the conventional CMR protocol and its findings in MI patients. Next, we looked at how nanoparticles can help in the imaging of MI and give an overview of the major approaches currently explored. Based on the presentation of successful nanoparticle applications as contrast agents (CAs) in preclinical and clinical models, we discuss promises and outstanding challenges facing the field of CMR in MI, their translational potential and clinical application.

Anomalous left main coronary artery detected by CT angiography.

The growing improvements of computed tomography have made this technique more and more available for cardiac evaluation. Coronary artery anomalies (CAAs) are often incidental findings in subjects with suspected coronary artery disease (CAD) undergoing coronary angiography or computed tomography coronary angiography (CTCA). In some cases, CAAs can be clinically relevant so their identification could change radically patient management and treatment. We report the case of a 68-year-old male patient with known CAD and associated anomalous origination of the left coronary artery from the opposite sinus.

Low correlation between biometric parameters, cardiovascular risk factors and aortic dimensions by computed tomography coronary angiography.

To analyze the relationship between aortic measures and biometric parameters in a large cohort of consecutive patients undergoing computed tomography coronary angiography.1170 patients (717 men/453 women) performing computed tomography coronary angiography for coronary evaluation were retrospectively evaluated. Aortic diameters and areas were measured at reproducible anatomic landmarks, perpendicular to the axis of vessel, at the level of the aortic root (AoR), the sinotubular junction (STJ), and the tubular ascending aorta (TAo). Biometric parameters and cardiovascular risk factors were recorded.The average values of AoR, STJ, and TAo were 35.63 ±â€Š5.00 mm, 30.56 ±â€Š4.82 mm, 35.07 ±â€Š5.84 mm. Hypertension was significantly associated with aortic dimensions.Aortic measures were significantly different between men and women (37.56 ±â€Š4.77 mm vs 32.58 ±â€Š3.68 mm for AoR, 31.88 ±â€Š4.84 mm vs 28.47 ±â€Š3.98 mm for STJ and 35.93 ±â€Š5.86 mm vs 33.70 ±â€Š5.54 mm for TAo) (P < .001) and linearly increased with age. Low Spearman correlation coefficients were found and the correlation of TAo diameters with age displayed the highest values (ρ = 0.372 for male and ρ = 0.373 for female, P < .001). Multiple linear regression analysis models were compared by R. The best model used body surface area (BSA) and age as independent variables and TAo diameter as dependent variable (R = 0.29 for AoR; R = 0.21 for STJ, and R = 0.20 for TAo).In conclusion, in our population low correlation between aortic dimensions and biometric parameters highlights the difficulty of identifying normal ranges, as well as issues related to normalization using conventional biometric parameters.

A case report of right coronary artery agenesis diagnosed by computed tomography coronary angiography.

INTRODUCTION: Single coronary artery is a rare condition characterized by the origin of a coronary that supplies the entire heart from a single coronary ostium. PATIENT CONCERNS: A 45-year-old woman with an altered exercise testing was addressed to a computed tomography coronary angiography (CTCA) to rule out coronary artery disease (CAD). DIAGNOSIS: CTCA examination showed the absence of the right coronary artery (RCA). The left anterior descending artery and the left circumflex artery (LCX) presented regular origin and course and LCX provided the posterior interventricular artery and the posterolateral artery. INTERVENTIONS: As CTCA highlighted the absence of potentially life-threatening features related to coronary anomaly, no surgical treatment was advised. OUTCOMES: The patient was dismissed, kept under pharmacological control and monitored over time. CONCLUSION: CTCA is the first-choice imaging modality in patients with ECG abnormalities properly allowing the differential diagnosis between CAD and congenital heart disease.

Normal patterns of left ventricle rest myocardial perfusion assessed by third-generation cardiac computed tomography.

PURPOSE: To investigate diastolic and systolic patterns of segmental and transmural rest perfusion of the left ventricle (LV) in normal subjects (NS) undergoing third-generation dual-source cardiac computed tomography (CCT). METHODS: Forty consecutive NS, with normal coronary arteries and cardiac chambers both anatomically and functionally on the basis of CCT, were retrospectively enrolled in the study. Relative normalized myocardial attenuation density (rnMAD) and transmural perfusion ratio (TPR) were calculated in diastole and systole for each segment and layer of the LV and then pooled into territories. RESULTS: Statistical analysis showed that sub-endocardial rnMAD was significantly higher than intra-myocardial and sub-epicardial for all myocardial territories both in systolic and diastolic phases (P<0·001). Basal and mid-ventricular rnMAD were higher than apical for all myocardial layers (P<0·001). Septum displayed higher rnMAD in intra-myocardium and sub-epicardium (179 ± 61 and 170 ± 59 in diastole and 172 ± 60 and 166 ± 58 in systole, respectively) than the anterior, lateral and inferior wall (P<0·001). Diastolic and systolic TPR were significantly different for the anterior and lateral wall (P<0·001), while septal TPR (1·06 ± 0·06 in diastole and 1·05 ± 0·06 in systole, respectively) was the lowest as compared to other territories' TPR. Finally, basal, mid-ventricular and apical TPR showed a significant linear trend with basal lower than mid-ventricular and apical values. CONCLUSION: Inter-territory and inter-layer myocardial perfusion differences can be accurately assessed with CCT in NS. This assessment is the basic step to further evaluate abnormal rest perfusion patterns in ischaemic and non-ischaemic diseases.

Case report of coronary artery fistula: Added value of multimodal advanced imaging with cardiac computed tomography and cardiac magnetic resonance.

RATIONALE: Unlike invasive coronary angiography and echocardiography, cardiac computed tomography (CCT) and cardiac magnetic resonance (CMR) imaging allow a coronary artery fistula (CAF) comprehensive evaluation focusing on both coronary and myocardial findings. PATIENT CONCERNS: We present the case of an asymptomatic patient suspected for CAF and referred to our structure for cardiovascular evaluation. DIAGNOSIS: The patient was diagnosed a CAF without coronary artery disease on the basis of CMR and CCT. INTERVENTIONS: The patient underwent an invasive coronary angiography after which the medical staff decided not to surgically treat the CAF. Therefore, a conservative treatment was chosen with strict temporal monitoring. OUTCOMES: After less than 1 year follow-up, the patient presented stable conditions without complaints. LESSONS: Multimodal non-invasive imaging has a key role in patient assessment for disease diagnosis providing better understanding for prognosis and treatment.

Radiolabeled PET/MRI Nanoparticles for Tumor Imaging.

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.

Water-Mediated Nanostructures for Enhanced MRI: Impact of Water Dynamics on Relaxometric Properties of Gd-DTPA.

Recently, rational design of a new class of contrast agents (CAs), based on biopolymers (hydrogels), have received considerable attention in Magnetic Resonance Imaging (MRI) diagnostic field. Several strategies have been adopted to improve relaxivity without chemical modification of the commercial CAs, however, understanding the MRI enhancement mechanism remains a challenge. Methods: A multidisciplinary approach is used to highlight the basic principles ruling biopolymer-CA interactions in the perspective of their influence on the relaxometric properties of the CA. Changes in polymer conformation and thermodynamic interactions of CAs and polymers in aqueous solutions are detected by isothermal titration calorimetric (ITC) measurements and later, these interactions are investigated at the molecular level using NMR to better understand the involved phenomena. Water molecular dynamics of these systems is also studied using Differential Scanning Calorimetry (DSC). To observe relaxometric properties variations, we have monitored the MRI enhancement of the examined structures over all the experiments. The study of polymer-CA solutions reveals that thermodynamic interactions between biopolymers and CAs could be used to improve MRI Gd-based CA efficiency. High-Pressure Homogenization is used to obtain nanoparticles. Results: The effect of the hydration of the hydrogel structure on the relaxometric properties, called Hydrodenticity and its application to the nanomedicine field, is exploited. The explanation of this concept takes place through several key aspects underlying biopolymer-CA's interactions mediated by the water. In addition, Hydrodenticity is applied to develop Gadolinium-based polymer nanovectors with size around 200 nm with improved MRI relaxation time (10-times). Conclusions: The experimental results indicate that the entrapment of metal chelates in hydrogel nanostructures offers a versatile platform for developing different high performing CAs for disease diagnosis.

Correlation of Circulating miR-765, miR-93-5p, and miR-433-3p to Obstructive Coronary Heart Disease Evaluated by Cardiac Computed Tomography.

Epigenetic-sensitive mechanisms may be correlated both to pathogenesis and prognosis of coronary heart disease (CHD). We prospectively investigated some plasma circulating microRNA levels in patients undergoing cardiac computed tomography for suspected CHD (n = 95). We show that let-7c-5p, miR-765, miR-483-5p, miR-31-5p, and miR-206 were upregulated in CHD patients (n = 66) versus healthy subjects HS (n = 29); moreover, let-7c-5p, miR-765, miR- 483-5p showed higher expression in obstructive CHD (n = 36) compared to no obstructive CHD patients (n = 66). Remarkably, miR-765, miR-93-5p, and miR-433-3p showed an upregulation in patients with critical coronary stenosis. Multivariate regression analysis demonstrated that miR-765, miR-31-5p, and miR-206 were independently associated with CHD while circulating levels of miR-765 (p = 0.035), miR-433-3p (p = 0.043), and miR-93-5p (p = 0.041) were significantly higher in critical stenosis patients. Receiver operating characteristic curve analysis revealed a good performance for miR-765, miR-93-5p, and miR-433-3p on predicting CHD severity. In conclusion, our study represents a combined epigenetic/imaging approach useful to support the diagnosis and prediction of CHD.

Evidence of association of circulating epigenetic-sensitive biomarkers with suspected coronary heart disease evaluated by Cardiac Computed Tomography.

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.

Quantification of epicardial fat with cardiac CT angiography and association with cardiovascular risk factors in symptomatic patients: from the ALTER-BIO (Alternative Cardiovascular Bio-Imaging markers) registry.

PURPOSE: We aimed to assess the association between features of epicardial adipose tissue and demographic, morphometric and clinical data, in a large population of symptomatic patients with clinical indication to cardiac computed tomography (CT) angiography. METHODS: Epicardial fat volume (EFV) and adipose CT density of 1379 patients undergoing cardiac CT angiography (918 men, 66.6%; age range, 18-93 years; median age, 64 years) were semi-automatically quantified. Clinical variables were compared between diabetic and nondiabetic patients to assess potential differences in EFV and adipose CT density. Multiple regression models were calculated to find the clinical variables with a significant association with EFV and adipose CT density. RESULTS: The median EFV in diabetic patients (112.87 mL) was higher compared with nondiabetic patients (82.62 mL; P < 0.001). The explanatory model of the multivariable analysis showed the strongest associations between EFV and BMI (ß=0.442) and age (ß=0.365). Significant yet minor association was found with sex (ß=0.203), arterial hypertension (ß=0.072), active smoking (ß=0.068), diabetes (ß=0.068), hypercholesterolemia (ß=0.046) and cardiac height (ß=0.118). The mean density of epicardial adipose tissue was associated with BMI (ß=0.384), age (ß=0.105), smoking (ß=0.088), and diabetes (ß=0.085). CONCLUSION: In a large population of symptomatic patients, EFV is higher in diabetic patients compared with nondiabetic patients. Clinical variables are associated with quantitative features of epicardial fat.

Image Quality and Dose Reduction by Dual Source Computed Tomography Coronary Angiography: Protocol Comparison.

PURPOSE: To compare image quality and radiation dose among different protocols in patients who underwent a 128-slice dual source computed tomography coronary angiography (DSCT-CTCA). METHODS: Ninety patients were retrospectively grouped according to heart rate (HR): 26 patients (group A) with stable HR ≤60 bpm were acquired using high pitch spiral mode (FLASH); 48 patients (group B) with irregular HR ≤60 bpm or stable HR between 60 and 70 bpm using step and shoot mode; and 16 patients (group C) with irregular HR >60 bpm or stable HR ≥70 bpm by retrospective electrocardiogram pulsing acquisition. Signal to noise ratio (SNR) and contrast to noise ratio (CNR) were measured for the main vascular structures. Moreover, the dose-length product and the effective dose were assessed. RESULTS: Both SNR and CNR were higher in group A compared to group C (18.27 ± 0.32 vs 11.22 ± 0.50 and 16.75 ± 0.32 vs 10.17 ± 0.50; P = .001). The effective dose was lower in groups A and B (2.09 ± 1.27 mSv and 4.60 ± 2.78 mSv, respectively) compared to group C (9.61 ± 5.95 mSv) P < .0001. CONCLUSION: The correct selection of a low-dose, HR-matched CTCA scan protocol with a DSCT scanner provides substantial reduction of radiation exposure and better SNR and CNR.

Influence of image reconstruction parameters on cardiovascular risk reclassification by Computed Tomography Coronary Artery Calcium Score.

OBJECTIVE: To investigate the influence of different CT reconstruction parameters on coronary artery calcium scoring (CACS) values and reclassification of predicted cardiovascular (CV) risk. METHODS: CACS was evaluated in 113 patients undergoing ECG-gated 64-slice CT. Reference CACS protocol included standard kernel filter (B35f) with slice thickness/increment of 3/1.5 mm, and field-of-view (FOV) of 150-180 mm. Influence of different image reconstruction algorithms (reconstructed slice thickness/increment 2.0/1.0-1.5/0.8-3.0/2.0-3.0/3.0 mm; slice kernel B30f-B45f; FOV 200-250 mm) on Agatston score was assessed by Bland-Altman plots and concordance correlation coefficient (CCC) analysis. Classification of CV risk was based on the Mayo Clinic classification. RESULTS: Different CACS reconstruction parameters showed overall good accuracy and precision when compared with reference protocol. Protocols with larger FOV, thinner slices and sharper kernels were associated with significant CV risk reclassification. Use of kernel B45f showed a moderate positive correlation with reference CACS protocol (Agatston CCC = 0.67), and yielded significantly higher CACS values (p < .05). Reconstruction parameters using B30f or B45f kernels, 250 mm FOV, or slice thickness/increment of 2.0/1.0 mm or 1.5/0.8 mm, were associated with significant reclassification of CV risk (p < .05). CONCLUSIONS: Kernel, FOV, slice thickness and increment are major determinants of accuracy and precision of CACS measurement. Despite high agreement and overall good correlation of different reconstruction protocols, thinner slices thickness and increment, and sharper kernels were associated with significant upward reclassification of CV risk. Larger FOV determined both upward and downward reclassification of CV risk.

In Vivo and In Vitro Analysis in Coronary Artery Disease Related to Type 2 Diabetes.

AIM: The leading cause of morbidity and mortality in patients with type 2 diabetes mellitus (DM) is coronary artery disease (CAD), a condition often asymptomatic but severe in these patients. Although glucose metabolism impairment and oxidative stress are known actors in the endothelial dysfunction/remodeling that occurs in diabetic patients, the relationship between cardiovascular disorders and DM is not fully understood. We have performed both an in vivo imaging and in vitro molecular analysis to investigate diabetic-specific CAD alterations. METHODS: Computed tomography coronary angiography (CTCA) was performed in a group of 20 diabetic patients with CAD (DM+CAD+), 20 non-diabetic with CAD (DM-CAD+), 10 diabetic non-CAD patients (DM+CAD-), and 20 non-diabetic healthy subjects (HS). Imaging quantitative parameters such as calcium score (Cascore), calcified plaque volume (CPV), non-calcified plaque volume (NCPV), total plaque volume (TPV), remodeling index (RI), and plaque burden were extracted for each CAD subject. Moreover, the expression levels of superoxide dismutase 2 (SOD2) and liver X receptor alpha (LXRα) genes were analyzed in the peripheral blood mononuclear cells, whereas hyaluronan (HA) concentrations were evaluated in the plasma of each subject. RESULTS: Imaging parameters, such as Cascore, CPV, RI, and plaque burden, were significantly higher in DM+CAD+ group, compared to DM-CAD+ (P = 0.019; P = 0.014; P < 0.001, P < 0.001, respectively). SOD2 mRNA was downregulated, while LXRα gene expression was upregulated in DM+CAD-, DM+CAD+, and DM-CAD+ groups compared to HS (P = 0.001, P = 0.03, and P = 0.001 for SOD2 and P = 0.006, P = 0.008, and P < 0.001 for LXRα, respectively). Plasmatic levels of HA were higher in DM-CAD+, DM+CAD-, and DM+CAD+ groups, compared to HS (P = 0.001 for the three groups). When compared to DM-CAD+, HA concentration was higher in DM+CAD- (P = 0.008) and DM+CAD+ (P < 0.001) with a significant difference between the two diabetic groups (P = 0.003). Moreover, HA showed a significant association with diabetes (P = 0.01) in the study population, and the correlation between HA levels and glycemia was statistically significant (ρ = 0.73, P < 0.001). CONCLUSION: In our population, imaging parameters highlight a greater severity of CAD in diabetic patients. Among molecular parameters, HA is modulated by diabetic CAD-related alterations while SOD2 and LXRα are found to be more associated with CAD but do not discriminate between diabetic and non-diabetic subgroups.

Hydrodenticity to enhance relaxivity of gadolinium-DTPA within crosslinked hyaluronic acid nanoparticles.

AIM: The efficacy of gadolinium (Gd) chelates as contrast agents for magnetic resonance imaging remains limited owing to poor relaxivity and toxic effects. Here, the effect of the hydration of the hydrogel structure on the relaxometric properties of Gd-DTPA is explained for the first time and called Hydrodenticity. RESULTS: The ability to tune the hydrogel structure is proved through a microfluidic flow-focusing approach able to produce crosslinked hyaluronic acid nanoparticles, analyzed regarding the crosslink density and mesh size, and connected to the characteristic correlation times of the Gd-DTPA. CONCLUSION: 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].

Coronary artery aneurysms detected by computed tomography coronary angiography.

AIMS: Coronary artery aneurysms (CAAs) are incidentally revealed by coronary angiography and consist in a localized dilation of a coronary artery. Although invasive coronary angiography (ICA) is the gold standard imaging technique, it can lead to the underestimation of CAAs diameter in presence of parietal thrombi. Computed tomography coronary angiography (CTCA) is a very sensitive tool in CAAs detection and provides a clear visualization of coronary lumen highlighting intraluminal thrombi. METHODS AND RESULTS: We retrospectively reviewed 390 CTCA performed at our institution, 9 patients (6 men, 3 women) resulted affected by CAAs and represented the aneurysmal group (A group). Matched controls were identified among the non-aneurysmal patients with healthy coronaries to CTCA (NAH group). Clinical variables and imaging findings were compared and correlated. CAAs prevalence in our population was 2.31%. 15 CAAs were detected, mainly on the right coronary artery (RCA) (9 aneurysms) followed by the left anterior descending coronary artery (LAD) (three aneurysms) and the left circumflex coronary artery (CX) (three aneurysms). In six patients (66.7%) CTCA displayed an aneurysmal thrombosis and in 5 patients (55.5%) CAAs were associated to coronary artery stenoses. A statistically significant difference was found between the diameters of coronary vessels measured in healthy segments in A and NAH group. CONCLUSIONS: 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.

An integrated approach to coronary heart disease diagnosis and clinical management.

The major issue in coronary heart disease (CHD) diagnosis and management is that symptoms onset in an advanced state of disease. Despite the availability of several clinical risk scores, the prediction of cardiovascular events is lacking, and many patients at risk are not well stratified according to the canonical risk factors alone. Therefore, adequate risk assessment remains the most challenging issue. Recently, the integration of imaging data with biochemical markers in a radiogenomic framework has been proposed in many fields of medicine as well as in cardiology. Multimodal imaging and advanced processing techniques can provide both direct (e.g., remodeling index, calcium score, total plaque volume, plaque burden) and indirect (e.g., myocardial perfusion index, coronary flow reserve) imaging features of CHD. Furthermore, the identification of novel non-invasive biochemical markers, mainly focused on plasma and/or serum samples, has increased the specificity of findings, reflecting several pathophysiological pathways of atherosclerosis, the principal actor in CHD. In this context, a multifaced approach, derived from the strengths of all these modalities, appears promising for finer risk stratification and treatment strategies, facilitating the decision-making and clinical management of patients. This review underlines the role of different imaging modalities in the quantification of coronary atherosclerosis and describes novel blood-based markers that could improve diagnosis and have a better predictive value in CHD.