ABSTRACT
In this study, we introduce a novel family of symmetrical thiophene-based small molecules with a Donor-Acceptor-Donor structure. These compounds feature three different acceptor units: benzo[c][1,2,5]thiadiazole (Bz), thieno[3,4-b]pyrazine (Pz), and thieno[1,2,5]thiadiazole (Tz), coupled with electron donor units based on a carbazole-thiophene derivative. Using Density Functional Theory (DFT), we investigate how the molecular geometry and strength of the central acceptor unit impact the redox and spectroscopic properties. Notably, the incorporation of Pz and Tz moieties induces a significant redshift in the absorption and emission spectra, which extend into the near-infrared (NIR) region, simultaneously reducing their energy gaps (~1.4-1.6â eV). This shift is attributed to the increased coplanarity of the oligomeric inner core, both in the ground (S0 ) and excited (S1 ) states, due to the enhanced quinoidal character as supported by bond-length alternation (BLA) analysis. These structural changes promote better π-electron delocalization and facilitate photoinduced charge transfer processes in optoelectronic devices. Notably, we show that Pz- and Tz-containing molecules exhibit NIR electrochromic behavior and present ambivalent character in bulk heterojunction (BHJ) solar cells. Finally, theoretical calculations suggest that these molecules could serve as effective two-photon absorption (2PA) probes, further expanding their potential in optoelectronic applications.
ABSTRACT
Novel optically active oligothiophenes bearing electron-donating chiral side chains have been prepared by synthetic methods suitable to achieve regioregular head-to-tail and head-to-head/tail-to-tail derivatives. In particular, the chiral (S)-(2-methyl)butyl moiety was linked at position 3 of the thiophene ring through heteroatoms, such as S or O, to evaluate its effect on the macro molecular aggregation and, consequently, on the chiroptical properties of the material in the solid state. The materials have been fully characterized and investigated by optical and chiroptical methods upon aggregation both from the solution and as cast films. Compared with the related head-to-tail and head-to-head/tail-to-tail poly(3-alkyl)thiophene derivatives, with the same optically active moiety directly linked to the ring and possessing a higher polymerization degree, the chiroptical properties of the newly synthesized oligomers were significant, or even better, and provided insight into the role of intrachain-interchain interactions between the heteroatom and the thienyl sulfur atom.
Subject(s)
Thiophenes/chemistry , Acetonitriles/chemistry , Circular Dichroism , Magnetic Resonance Spectroscopy , Oxygen/chemistry , Polymerization , Solutions , Spectrophotometry, Infrared , Spectrophotometry, Ultraviolet , Stereoisomerism , Sulfur/chemistry , Thiophenes/chemical synthesisABSTRACT
OBJECTIVE: Circulating levels of high-sensitivity cardiac troponin T (hs-cTnT) and N terminal pro brain natriuretic peptide (NT-proBNP) are predictors of prognosis in patients with coronary artery disease (CAD). We aimed at evaluating the effect of coronary atherosclerosis and myocardial ischemia on cardiac release of hs-cTnT and NT-proBNP in patients with suspected CAD. APPROACH AND RESULTS: Hs-cTnT and NT-proBNP were measured in 378 patients (60.1±0.5 years, 229 males) with stable angina and unknown CAD enrolled in the Evaluation of Integrated Cardiac Imaging (EVINCI) study. All patients underwent stress imaging to detect myocardial ischemia and coronary computed tomographic angiography to assess the presence and characteristics of CAD. An individual computed tomographic angiography score was calculated combining extent, severity, composition, and location of plaques. In the whole population, the median (25-75 percentiles) value of plasma hs-cTnT was 6.17 (4.2-9.1) ng/L and of NT-proBNP was 61.66 (31.2-132.6) ng/L. In a multivariate model, computed tomographic angiography score was an independent predictor of the plasma hs-cTnT (coefficient 0.06, SE 0.02; P=0.0089), whereas ischemia was a predictor of NT-proBNP (coefficient 0.38, SE 0.12; P=0.0015). Hs-cTnT concentrations were significantly increased in patients with CAD with or without myocardial ischemia (P<0.005), whereas only patients with CAD and ischemia showed significantly higher levels of NT-proBNP (P<0.001). CONCLUSIONS: In patients with stable angina, the presence and extent of coronary atherosclerosis is related with circulating levels of hs-cTnT, also in the absence of ischemia, suggesting an ischemia-independent mechanism of hs-cTnT release. Obstructive CAD causing myocardial ischemia is associated with increased levels of NT-proBNP.
Subject(s)
Angina, Stable/blood , Coronary Artery Disease/blood , Myocardial Ischemia/blood , Natriuretic Peptide, Brain/blood , Peptide Fragments/blood , Troponin T/blood , Angina, Stable/diagnosis , Biomarkers/blood , Chi-Square Distribution , Coronary Angiography/methods , Coronary Artery Disease/diagnosis , Echocardiography, Stress , Europe , Female , Humans , Linear Models , Magnetic Resonance Imaging , Male , Middle Aged , Multivariate Analysis , Myocardial Ischemia/diagnosis , Myocardial Perfusion Imaging , Positron-Emission Tomography , Predictive Value of Tests , Severity of Illness Index , Tomography, Emission-Computed, Single-Photon , Tomography, X-Ray ComputedABSTRACT
UNLABELLED: The objective of this study was to develop an automatic image registration technique capable of compensating for kidney motion in renal perfusion MRI, to assess the effect of renal artery stenosis on the kidney parenchyma. MATERIALS AND METHODS: Images from 20 patients scheduled for a renal perfusion study were acquired using a 1.5 T scanner. A free-breathing 3D-FSPGR sequence was used to acquire coronal views encompassing both kidneys following the infusion of Gd-BOPTA. A two-step registration algorithm was developed, including a preliminary registration minimising the quadratic difference and a fine registration maximising the mutual information (MI) between consecutive image frames. The starting point for the MI-based registration procedure was provided by an adaptive predictor that was able to predict kidney motion using a respiratory movement model. The algorithm was validated against manual registration performed by an expert user. RESULTS: The mean distance between the automatically and manually defined contours was 2.95 ± 0.81 mm, which was not significantly different from the interobserver variability of the manual registration procedure (2.86 ± 0.80 mm, P = 0.80). The perfusion indices evaluated on the manually and automatically extracted perfusion curves were not significantly different. CONCLUSIONS: The developed method is able to automatically compensate for kidney motion in perfusion studies, which prevents the need for time-consuming manual image registration.
Subject(s)
Image Interpretation, Computer-Assisted/methods , Magnetic Resonance Angiography/methods , Pattern Recognition, Automated/methods , Renal Artery Obstruction/physiopathology , Renal Artery/physiopathology , Renal Circulation , Subtraction Technique , Adolescent , Adult , Aged , Blood Flow Velocity , Feedback , Humans , Middle Aged , Renal Artery/pathology , Renal Artery Obstruction/diagnosis , Reproducibility of Results , Sensitivity and Specificity , Young AdultABSTRACT
Hybrid PET/CT scanners can simultaneously visualize coronary artery disease as revealed by computed tomography (CT) and myocardial perfusion as measured by positron emission tomography (PET). Manual registration is usually required in clinical practice to compensate spatial mismatch between datasets. In this paper, we present a registration algorithm that is able to automatically align PET/CT cardiac images. The algorithm bases on mutual information (MI) as registration metric and on genetic algorithm as optimization method. A multiresolution approach was used to optimize the processing time. The algorithm was tested on computerized models of volumetric PET/CT cardiac data and on real PET/CT datasets. The proposed automatic registration algorithm smoothes the pattern of the MI and allows it to reach the global maximum of the similarity function. The implemented method also allows the definition of the correct spatial transformation that matches both synthetic and real PET and CT volumetric datasets.
Subject(s)
Algorithms , Image Interpretation, Computer-Assisted/methods , Imaging, Three-Dimensional/methods , Multimodal Imaging/methods , Positron-Emission Tomography , Tomography, X-Ray Computed , Coronary Artery Disease/diagnosis , Coronary Artery Disease/diagnostic imaging , Humans , Myocardial Perfusion Imaging/methods , Myocardium/pathology , Reproducibility of Results , Sensitivity and SpecificityABSTRACT
The integration of complementary information from different medical imaging techniques opened, since the 90s, new scenarios and possibilities for non-invasive diagnosis. The anatomo-functional information obtained with the image fusion (i.e., by composing PET and CT or SPECT and CT), is greater than the sum of information given by each modality, and allows quantitative evaluation of functional parameters through the application of specific model-based image processing. Before the introduction of integrated multimodal scanners from most manufacturers (hardware fusion), many software techniques have been used to allow image fusion from different modalities; such methods of software fusion is still important for all modalities that cannot by merged in a single scanner, or whenever the patient movement can introduce inter-modality misalignments within the same exam in an integrated scanner or if each modality is utilized at different times and on separate scanners. This article summarizes the software and hardware evolution of clinical and preclinical hybrid imaging, and discusses the outcome of this technology in the clinical environment with particular emphasis on the cardiovascular application.
Subject(s)
Diagnostic Imaging/methods , Diagnostic Imaging/trends , Software , Forecasting , Humans , Systems IntegrationABSTRACT
Four new conjugated polymers alternating benzothiadiazole units and thiophene moieties functionalized with ionic phosphonium or sulfonic acid salts in the side chains were synthesized by a postfunctionalization approach of polymeric precursors. The introduction of ionic groups makes the conjugated polymers soluble in water and/or polar solvents, allowing for the fabrication of bulk heterojunction (BHJ) solar cells using environmentally friendly conditions. All polymers were fully characterized by spectroscopic, thermal, electrochemical, X-ray diffraction, scanning electron, and atomic force techniques. BHJ solar cells were obtained from halogen-free solvents (i.e., ethanol and/or anisole) by blending the synthesized ionic push-pull polymers with a serinol-fullerene derivative or an ionic homopolymer acting as electron-acceptor (EA) or electron-donor (ED) counterparts, respectively. The device with the highest optical density and the smoothest surface of the active layer was the best-performing, showing a 4.76% photoconversion efficiency.
ABSTRACT
A new side-chain C60-fullerene functionalized thiophene copolymer bearing tributylphosphine-substituted hexylic lateral groups was successfully synthesized by means of a fast and effective post-polymerization reaction on a regioregular ω-alkylbrominated polymeric precursor. The growth of the polymeric intermediate was followed by NMR spectrometry in order to determine the most convenient reaction time. The obtained copolymer was soluble in water and polar solvents and was used as a photoactive layer in single-material organic photovoltaic (OPV) solar cells. The copolymer photovoltaic efficiency was compared with that of an OPV cell containing a water-soluble polythiophenic homopolymer, functionalized with the same tributylphosphine-substituted hexylic side chains, in a blend with a water-soluble C60-fullerene derivative. The use of a water-soluble double-cable copolymer made it possible to enhance the control on the nanomorphology of the active blend, thus reducing phase-segregation phenomena, as well as the macroscale separation between the electron acceptor and donor components. Indeed, the power conversion efficiency of OPV cells based on a single material was higher than that obtained with the classical architecture, involving the presence of two distinct ED and EA materials (PCE: 3.11% vs. 2.29%, respectively). Moreover, the synthetic procedure adopted to obtain single material-based cells is more straightforward and easier than that used for the preparation of the homopolymer-based BHJ solar cell, thus making it possible to completely avoid the long synthetic pathway which is required to prepare water-soluble fullerene derivatives.
ABSTRACT
PURPOSE: The combination of sequentially acquired cardiac PET and SPECT data integrating metabolic and perfusion information allows the assessment of myocardial viability, a relevant clinical parameter for the management of patients who have suffered myocardial infarction and are now candidates for complex and cost intensive therapies such as bypass surgery. However, registration of cardiac functional datasets acquired on different imaging systems is limited by the difficulty to define anatomical landmarks and by the relatively poor inherent spatial resolution. In this article, the authors sought to evaluate whether it is possible to automatically register FDG-PET and sestamibi-SPECT cardiac data. METHODS: Automatic rigid registration was implemented with the ITK framework using Mattes mutual information as the similarity measure and a quaternion to represent the rotational component. The goodness of the alignment was evaluated by computing the mean target registration error (mTRE) at the myocardial wall. The registration parameters were optimized for robustness and speed using the data from 11 cardiac patients undergoing both PET and SPECT examinations (training datasets). The optimized algorithm was applied on the PET and SPECT data from 11 further patients (evaluation datasets). Quantitative (mTRE calculation) and visual (scoring method) comparisons were performed between automatic and manual registrations. Moreover, the automatic registration was also compared to the registration implicitly defined in the standard clinical analysis. RESULTS: The registration parameters were successfully optimized and resulted in a mean mTRE of 1.13 mm and 1.2 s average runtime on standard computer hardware for the training datasets. Automatic registration in the 11 validation datasets resulted in an average mTRE of 2.3 mm, with 7.5 mm mTRE in the worst case and an average runtime of 1.6 s. Automatic registration outperformed manual registrations both for the mTRE and for the visual assessment. Automatic registration also resulted in higher accuracy and better visual assessment as compared to the registration implicitly performed in the standard clinical analysis. CONCLUSIONS: The results demonstrate the possibility to successfully perform mutual information based registration of PET and SPECT cardiac data, allowing an improved workflow for the sequentially acquired cardiac datasets, in general, and specifically for the assessment of myocardial viability.
Subject(s)
Image Interpretation, Computer-Assisted/methods , Myocardial Perfusion Imaging/methods , Myocardial Stunning/diagnosis , Positron-Emission Tomography/methods , Subtraction Technique , Tomography, Emission-Computed, Single-Photon/methods , Ventricular Dysfunction, Left/diagnosis , Algorithms , Humans , Image Enhancement/methods , Models, Biological , Models, Statistical , Myocardial Perfusion Imaging/instrumentation , Pattern Recognition, Automated/methods , Phantoms, Imaging , Positron-Emission Tomography/instrumentation , Reproducibility of Results , Sensitivity and Specificity , Tomography, Emission-Computed, Single-Photon/instrumentationABSTRACT
OBJECTIVES: Systemic sclerosis (SSc) causes functional and structural microcirculatory dysfunction, affecting also distal extremities. Optical Near-InfraRed Spectroscopy (NIRS) of blood HbO2 saturation (stO2) is able to evaluate O2 delivery/consumption balance in the explored tissue. The NIRS-sensitive camera non-invasively detects stO2 values in superficial tissues, automatically generating 2D-imaging maps in real time. We aimed at testing whether NIRS hand imaging may evaluate peripheral microcirculatory dysfunction and its spatial heterogeneity in SSc patients compared to controls. METHODS: Forty SSc patients (aged 55.1⯱â¯15.6 years) and twenty-one healthy controls (aged 54.3⯱â¯14.5years, pâ¯=â¯0.89) were studied by palmar hand NIRS-2D imaging. A blood pressure cuff was applied to the forearm and 3 min ischemia was induced. Images were acquired at basal conditions and every 10 seconds during 3 minutes of ischemia and 5 minutes of reperfusion. Five regions of interest were positioned on each fingertip, from the second to the fifth finger and one on the thenar eminence. RESULTS: A significant difference was found between controls and SSc patients in basal stO2 (84.3⯱â¯7.5â¯vs. 75.4⯱â¯10.9%, pâ¯<â¯0.001), minimum stO2 (65.2⯱â¯8.0â¯vs. 53.4⯱â¯10.1%, pâ¯<â¯0.001) and time to maximum stO2 during hyperemia (63⯱â¯38â¯vs. 85⯱â¯49â¯s, pâ¯<â¯0.05). Among clinical characteristics, anti-Scl70 antibody positivity, digital ulcers history and smoke exposure affected NIRS parameters, as well as sildenafil and statins therapy. Conversely, no significant differences were found in NIRS-2D values between different nailfold-videocapillaroscopy patterns. CONCLUSION: NIRS-2D imaging is a simple, automated tool to non-invasively detect regional microcirculatory impairment in SSc, which seems to add significant functional information to the morphological picture of nailfold-videocapillaroscopy.
Subject(s)
Hand/diagnostic imaging , Microcirculation/physiology , Oxygen Consumption/physiology , Scleroderma, Systemic/physiopathology , Adult , Aged , Case-Control Studies , Female , Hand/blood supply , Humans , Male , Middle Aged , Scleroderma, Systemic/diagnostic imaging , Spectroscopy, Near-Infrared/methodsABSTRACT
Interaction with machines is mediated by human-machine interfaces (HMIs). Brain-machine interfaces (BMIs) are a particular class of HMIs and have so far been studied as a communication means for people who have little or no voluntary control of muscle activity. In this context, low-performing interfaces can be considered as prosthetic applications. On the other hand, for able-bodied users, a BMI would only be practical if conceived as an augmenting interface. In this paper, a method is introduced for pointing out effective combinations of interfaces and devices for creating real-world applications. First, devices for domotics, rehabilitation and assistive robotics, and their requirements, in terms of throughput and latency, are described. Second, HMIs are classified and their performance described, still in terms of throughput and latency. Then device requirements are matched with performance of available interfaces. Simple rehabilitation and domotics devices can be easily controlled by means of BMI technology. Prosthetic hands and wheelchairs are suitable applications but do not attain optimal interactivity. Regarding humanoid robotics, the head and the trunk can be controlled by means of BMIs, while other parts require too much throughput. Robotic arms, which have been controlled by means of cortical invasive interfaces in animal studies, could be the next frontier for non-invasive BMIs. Combining smart controllers with BMIs could improve interactivity and boost BMI applications.
Subject(s)
Brain/physiology , Communication Aids for Disabled , Man-Machine Systems , User-Computer Interface , Computer Simulation , Electroencephalography , Feedback , Humans , Numerical Analysis, Computer-Assisted , Reaction TimeABSTRACT
Purpose: A clear link between obesity and brown adipose tissue (BAT) dysfunction has been recently demonstrated. The purpose of this pilot study is to determine if near-infrared spectroscopy (NIRS) 2D imaging together with infrared thermography (IRT) is capable of identifying thermal and vascular response in the supraclavicular (SCV) areas after the ingestion of an oral glucose load as a thermogenic stimulation. Method: We studied two groups of women (obese versus lean) for discerning their different responses. NIRS and IRT images were acquired on the neck in the left SCV region during a 3 h oral glucose tolerance test (OGTT) and immediately after a cold stimulation. Results: We detected a significant thermal response of BAT in SCV fossa in both groups. Both during OGTT and after cold stimulation, skin temperature was persistently higher in lean versus obese. This response was not coupled with changes in oxygen saturation of subcutaneous tissue in that area. Discussion and Conclusion: The results show that NIRS/IRT may be a novel, noninvasive, radiation-free, easy to use, and low-cost method for monitoring, during the standard clinical practice, the diet and pharmacological intervention which aims to stimulate BAT as a potential therapeutic target against obesity and diabetes.
Subject(s)
Adipose Tissue, Brown/diagnostic imaging , Multimodal Imaging/instrumentation , Multimodal Imaging/methods , Adult , Female , Humans , Pilot Projects , Spectroscopy, Near-InfraredABSTRACT
Collaborative and multicenter studies permit a large number of patients to be enrolled within a reasonable time and providing the opportunity to collect different data. Informatics platforms play an important role in management, storage, and exchange of data between the participants involved in the study. In this article, we describe a modular informatics platform designed and developed to support collaborative and multicenter studies in cardiology. In each developed module, data management is implemented following local defined protocols. The modular characteristic of the developed platform allows independent transfer of different kinds of data, such as biological samples, imaging raw data, and patients' digital information. Moreover, it offers safe central storage of the data collected during the study. The developed platform was successfully tested during a European collaborative and multicenter study, focused on evaluating multimodal non-invasive imaging to diagnose and characterize ischemic heart disease.
Subject(s)
Cardiology/instrumentation , Cooperative Behavior , Database Management Systems/instrumentation , Health Information Exchange/standards , Research Support as Topic/methods , Database Management Systems/standards , Humans , ItalyABSTRACT
AIMS: Hybrid imaging provides a non-invasive assessment of coronary anatomy and myocardial perfusion. We sought to evaluate the added clinical value of hybrid imaging in a multi-centre multi-vendor setting. METHODS AND RESULTS: Fourteen centres enrolled 252 patients with stable angina and intermediate (20-90%) pre-test likelihood of coronary artery disease (CAD) who underwent myocardial perfusion scintigraphy (MPS), CT coronary angiography (CTCA), and quantitative coronary angiography (QCA) with fractional flow reserve (FFR). Hybrid MPS/CTCA images were obtained by 3D image fusion. Blinded core-lab analyses were performed for CTCA, MPS, QCA and hybrid datasets. Hemodynamically significant CAD was ruled-in non-invasively in the presence of a matched finding (myocardial perfusion defect co-localized with stenosed coronary artery) and ruled-out with normal findings (both CTCA and MPS normal). Overall prevalence of significant CAD on QCA (>70% stenosis or 30-70% with FFR≤0.80) was 37%. Of 1004 pathological myocardial segments on MPS, 246 (25%) were reclassified from their standard coronary distribution to another territory by hybrid imaging. In this respect, in 45/252 (18%) patients, hybrid imaging reassigned an entire perfusion defect to another coronary territory, changing the final diagnosis in 42% of the cases. Hybrid imaging allowed non-invasive CAD rule-out in 41%, and rule-in in 24% of patients, with a negative and positive predictive value of 88% and 87%, respectively. CONCLUSION: In patients at intermediate risk of CAD, hybrid imaging allows non-invasive co-localization of myocardial perfusion defects and subtending coronary arteries, impacting clinical decision-making in almost one every five subjects.
Subject(s)
Coronary Artery Disease/diagnostic imaging , Fractional Flow Reserve, Myocardial/physiology , Image Interpretation, Computer-Assisted , Multimodal Imaging/methods , Myocardial Ischemia/diagnostic imaging , Aged , Cohort Studies , Computed Tomography Angiography/methods , Coronary Angiography/methods , Coronary Artery Disease/physiopathology , Europe , Female , Humans , Internationality , Male , Middle Aged , Myocardial Ischemia/physiopathology , Myocardial Perfusion Imaging/methods , Observer Variation , Positron-Emission Tomography/methods , Retrospective Studies , Sensitivity and Specificity , Statistics, Nonparametric , Tomography, Emission-Computed, Single-Photon/methodsABSTRACT
OBJECTIVES: Coronary computed tomography angiography (CTA) describes several features of coronary plaques, i.e. location, severity, and composition. Integrated CTA scores are able to identify individual patterns of higher risk. We sought to test whether circulating biomarkers related with metabolism and inflammation could predict high risk coronary anatomy at CTA in patients with stable chest pain. METHODS: We evaluated a panel of 17 biomarkers in 429 patients (60.3 ± 0.4 years, 268 males) with stable chest pain who underwent coronary CTA having been enrolled in the Evaluation of Integrated Cardiac Imaging (EVINCI) study. The individual CTA risk score was calculated combining plaque extent, severity, composition, and location. The presence and distribution of non-calcified, mixed and calcified plaques were analyzed in each patient. RESULTS: After adjustment for age, sex and medical treatment, high-density lipoprotein (HDL) cholesterol, leptin, and interleukin-6 (IL-6) were independent predictors of CTA risk score at multivariate analysis (P = 0.050, 0.002, and 0.007, respectively). Integrating these biomarkers with common clinical variables, a model was developed which showed a better discriminating ability than the Framingham Risk Score and the Euro-SCORE in identifying the patients with higher CTA risk score (area under the receiver-operating characteristics curve = 0.81, 0.63 and 0.71, respectively, P < 0.001). These three biomarkers were significantly altered in patients with mixed or non-calcified plaques. CONCLUSIONS: In patients with stable chest pain, low HDL cholesterol, low leptin and high IL-6 are independent predictors of high risk coronary anatomy as defined by an integrated CTA risk score.
Subject(s)
Angina, Stable/etiology , Cholesterol, HDL/blood , Coronary Angiography/methods , Coronary Artery Disease/blood , Coronary Artery Disease/diagnostic imaging , Coronary Vessels/diagnostic imaging , Inflammation Mediators/blood , Interleukin-6/blood , Leptin/blood , Tomography, X-Ray Computed , Biomarkers/blood , Coronary Artery Disease/complications , Female , Humans , Male , Middle Aged , Plaque, Atherosclerotic , Predictive Value of Tests , Risk Factors , Vascular Calcification/blood , Vascular Calcification/diagnostic imagingABSTRACT
BACKGROUND: In patients with chronic angina-like chest pain, the probability of coronary artery disease (CAD) is estimated by symptoms, age, and sex according to the Genders clinical model. We investigated the incremental value of circulating biomarkers over the Genders model to predict functionally significant CAD in patients with chronic chest pain. METHODS: In 527 patients (60.4 years, standard deviation, 8.9 years; 61.3% male participants) enrolled in the European Evaluation of Integrated Cardiac Imaging (EVINCI) study, clinical and biohumoral data were collected. RESULTS: Functionally significant CAD-ie, obstructive coronary disease seen at invasive angiography causing myocardial ischemia at stress imaging or associated with reduced fractional flow reserve (FFR < 0.8), or both-was present in 15.2% of patients. High-density lipoprotein (HDL) cholesterol, aspartate aminotransferase (AST) levels, and high-sensitivity C-reactive protein (hs-CRP) were the only independent predictors of disease among 31 biomarkers analyzed. The model integrating these biohumoral markers with clinical variables outperformed the Genders model by receiver operating characteristic curve (ROC) (area under the curve [AUC], 0.70 [standard error (SE), 0.03] vs 0.58 [SE, 0.03], respectively, P < 0.001) and reclassification analysis (net reclassification improvement, 0.15 [SE, 0.07]; P = 0.04). Cross-validation of the ROC analysis confirmed the discrimination ability of the new model (AUC, 0.66). As many as 56% of patients who were assigned to a higher pretest probability by the Genders model were correctly reassigned to a low probability class (< 15%) by the new integrated model. CONCLUSIONS: The Genders model has a low accuracy for predicting functionally significant CAD. A new model integrating HDL cholesterol, AST, and hs-CRP levels with common clinical variables has a higher predictive accuracy for functionally significant CAD and allows the reclassification of patients from an intermediate/high to a low pretest likelihood of CAD.
Subject(s)
Aspartate Aminotransferases/blood , C-Reactive Protein/analysis , Chest Pain/blood , Cholesterol, HDL/blood , Coronary Disease/blood , Aged , Analysis of Variance , Angina Pectoris/blood , Angina Pectoris/diagnosis , Angina Pectoris/epidemiology , Biomarkers/blood , Chest Pain/diagnosis , Chest Pain/epidemiology , Chronic Disease , Cohort Studies , Coronary Angiography/methods , Coronary Disease/diagnostic imaging , Coronary Disease/epidemiology , Female , Fractional Flow Reserve, Myocardial , Humans , Male , Middle Aged , Multivariate Analysis , Predictive Value of Tests , Prospective Studies , ROC Curve , Reproducibility of Results , Risk Assessment , Severity of Illness Index , Sex FactorsABSTRACT
BACKGROUND: The choice of imaging techniques in patients with suspected coronary artery disease (CAD) varies between countries, regions, and hospitals. This prospective, multicenter, comparative effectiveness study was designed to assess the relative accuracy of commonly used imaging techniques for identifying patients with significant CAD. METHODS AND RESULTS: A total of 475 patients with stable chest pain and intermediate likelihood of CAD underwent coronary computed tomographic angiography and stress myocardial perfusion imaging by single photon emission computed tomography or positron emission tomography, and ventricular wall motion imaging by stress echocardiography or cardiac magnetic resonance. If ≥1 test was abnormal, patients underwent invasive coronary angiography. Significant CAD was defined by invasive coronary angiography as >50% stenosis of the left main stem, >70% stenosis in a major coronary vessel, or 30% to 70% stenosis with fractional flow reserve ≤0.8. Significant CAD was present in 29% of patients. In a patient-based analysis, coronary computed tomographic angiography had the highest diagnostic accuracy, the area under the receiver operating characteristics curve being 0.91 (95% confidence interval, 0.88-0.94), sensitivity being 91%, and specificity being 92%. Myocardial perfusion imaging had good diagnostic accuracy (area under the curve, 0.74; confidence interval, 0.69-0.78), sensitivity 74%, and specificity 73%. Wall motion imaging had similar accuracy (area under the curve, 0.70; confidence interval, 0.65-0.75) but lower sensitivity (49%, P<0.001) and higher specificity (92%, P<0.001). The diagnostic accuracy of myocardial perfusion imaging and wall motion imaging were lower than that of coronary computed tomographic angiography (P<0.001). CONCLUSIONS: In a multicenter European population of patients with stable chest pain and low prevalence of CAD, coronary computed tomographic angiography is more accurate than noninvasive functional testing for detecting significant CAD defined invasively. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT00979199.
Subject(s)
Coronary Angiography/methods , Coronary Artery Disease/diagnosis , Coronary Stenosis/diagnosis , Echocardiography, Stress , Magnetic Resonance Imaging , Myocardial Perfusion Imaging/methods , Positron-Emission Tomography , Tomography, Emission-Computed, Single-Photon , Tomography, X-Ray Computed , Aged , Area Under Curve , Comparative Effectiveness Research , Coronary Artery Disease/diagnostic imaging , Coronary Artery Disease/epidemiology , Coronary Artery Disease/physiopathology , Coronary Stenosis/diagnostic imaging , Coronary Stenosis/epidemiology , Coronary Stenosis/physiopathology , Europe/epidemiology , Female , Fractional Flow Reserve, Myocardial , Humans , Male , Middle Aged , Predictive Value of Tests , Prevalence , Prospective Studies , ROC Curve , Severity of Illness Index , Ventricular FunctionABSTRACT
PURPOSE: Multimodal cardiac imaging by CTA and quantitative PET enables acquisition of patient-specific coronary anatomy and absolute myocardial perfusion at rest and during stress. In the clinical setting, integration of this information is performed visually or using coronary arteries distribution models. We developed a new tool for CTA and quantitative PET integrated 3D visualization, exploiting XML and DICOM clinical standards. METHODS: The hybrid image tool (HIT) developed in the present study included four main modules: (1) volumetric registration for spatial matching of CTA and PET data sets, (2) an interface to PET quantitative analysis software, (3) a derived DICOM generator able to build DICOM data set from quantitative polar maps, and (4) a 3D visualization tool of integrated anatomical and quantitative flow information. The four modules incorporated in the HIT tool communicate by defined standard XML files: XML-transformation and XML MIST standards. RESULTS: The HIT tool implements a 3D representation of CTA showing real coronary anatomy fused to PET-derived quantitative myocardial blood flow distribution. The technique was validated on 16 data sets from EVINCI study population. The validation of the method confirmed the high matching between "original" and derived data sets as well as the accuracy of the registration procedure. CONCLUSIONS: Three-dimensional integration of patient- specific coronary artery anatomy provided by CTA and quantitative myocardial blood flow obtained from PET imaging can improve cardiac disease assessment. The HIT tool introduced in this paper may represent a significant advancement in the clinical use of this multimodal approach.
Subject(s)
Coronary Disease/diagnostic imaging , Imaging, Three-Dimensional/methods , Multimodal Imaging , Positron-Emission Tomography , Radiographic Image Interpretation, Computer-Assisted/methods , Tomography, X-Ray Computed , Algorithms , Humans , SoftwareABSTRACT
AIMS: Pre-treating placenta-derived human mesenchymal stem cells (FMhMSCs) with a hyaluronan mixed ester of butyric and retinoic acid (HBR) potentiates their reparative capacity in rodent hearts. Our aim was to test FMhMSCs in a large-animal model by employing a novel combination of in vivo and ex vivo analyses. METHODS AND RESULTS: Matched regional quantifications of myocardial function and viability were performed by magnetic resonance imaging (MRI) and positron emission tomography (PET) 4 weeks after myocardial infarction combined with intramyocardial injection of FMhMSCs (n = 7), or HBR-pre-treated FMhMSCs (HBR-FMhMSCs, n = 6), or saline solution (PBS, n = 7). Sham-operated pigs (n = 4) were used as control animals. Despite no differences in the ejection fraction and haemodynamics, regional MRI revealed, in pigs treated with HBR-FMhMSCs compared with the other infarcted groups, a 40% smaller infarct scar size and a significant improvement of the end-systolic wall thickening and circumferential shortening of the infarct border zone. Consistently, PET showed that myocardial perfusion and glucose uptake were, respectively, 35 and 23% higher in the border zone of pigs treated with HBR-FMhMSCs compared with the other infarcted groups. Histology supported in vivo imaging; the delivery of HBR-FMhMSCs significantly enhanced capillary density and decreased fibrous tissue by approximately 68%. Moreover, proteomic analysis of the border zone in the HBR-FMhMSCs group and the FMhMSCs group indicated, respectively, 45 and 30% phenotypic homology with healthy tissue, while this homology was only 26% in the border zone of the PBS group. CONCLUSION: Our results support a more pronounced reparative potential of HBR-pre-treated FMhMSCs in a clinically relevant animal model of infarction and highlight the necessity of using combined diagnostic imaging to avoid underestimations of stem cell therapeutic effects in the heart.
Subject(s)
Hyaluronic Acid/analogs & derivatives , Mesenchymal Stem Cell Transplantation/methods , Mesenchymal Stem Cells/drug effects , Myocardial Infarction/therapy , Animals , Butyric Acid/pharmacology , Esters/pharmacology , Female , Humans , Hyaluronic Acid/pharmacology , Magnetic Resonance Imaging, Cine , Male , Myocardial Infarction/pathology , Myocardial Infarction/physiopathology , Placenta/cytology , Positron-Emission Tomography , Pregnancy , Proteomics , Sus scrofa , Tretinoin/pharmacology , Ventricular Function, LeftABSTRACT
BACKGROUND: Left bundle branch block (LBBB) influences on regional left ventricular (LV) structure, perfusion, and metabolism have not yet been thoroughly investigated in dilated cardiomyopathy patients. METHODS AND RESULTS: Eleven dilated cardiomyopathy patients with LBBB (mean+/-SD age, 62+/-11 years; LV ejection fraction, 35+/-8%) and 7 dilated cardiomyopathy patients without LBBB (mean+/-SD age, 58+/-9 years; LV ejection fraction, 37+/-10%) were studied by cardiac magnetic resonance and positron emission tomography. The left ventricle was divided in 3 regions: septum, adjacent (anterior-inferior walls), and lateral. Regional midwall circumferential strain, maximum shortening, and strain rate were obtained from tagged cardiac magnetic resonance. The systolic stretch index was calculated as positive strain rate (stretching) divided by total strain rate. Myocardial metabolic rate of glucose and resting and hyperemic myocardial blood flow were quantified by 2-[(18)F]fluoro-2-deoxyglucose and [(13)N]ammonia positron emission tomography, respectively. Compared with non-LBBB patients, LBBB patients showed a highly inhomogeneous systolic deformation pattern that changed gradually, moving from a discoordinate [(systolic stretch index, 0.485 (0.284)] and poorly contracting (maximum shortening, -1.14+/-0.96%) septum to a coordinate [systolic stretch index, 0.002 (0.168)] and strongly contracting (maximum shortening, -13.63+/-2.58%) lateral region (both P<0.0001). This pattern was closely matched to the myocardial metabolic rate of glucose, disclosing lowest, intermediate, and highest values in the septum, adjacent, and lateral regions, respectively (P<0.0001). Septal-to-lateral thickness ratio was lower in LBBB than in non-LBBB patients (P=0.03). In both groups, the LV distribution of resting and hyperemic myocardial blood flow and myocardial blood flow reserve did not differ significantly. CONCLUSIONS: In dilated cardiomyopathy patients, the extensive LV contraction abnormalities induced by LBBB cause regional myocardial metabolic and structural remodeling, without consistent changes in blood flow.