Martina Marinelli

Detection of significant coronary artery disease by noninvasive anatomical and functional imaging.

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.

Defining brain-machine interface applications by matching interface performance with device requirements

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.

Placental stem cells pre-treated with a hyaluronan mixed ester of butyric and retinoic acid to cure infarcted pig hearts: a multimodal study.

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.

Myocardial Structural, Perfusion, and Metabolic Correlates of Left Bundle Branch Block Mechanical Derangement in Patients With Dilated Cardiomyopathy A Tagged Cardiac Magnetic Resonance and Positron Emission Tomography Study

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-[18F]fluoro-2-deoxyglucose and [13N]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.

Multicentre multi-device hybrid imaging study of coronary artery disease: results from the EValuation of INtegrated Cardiac Imaging for the Detection and Characterization of Ischaemic Heart Disease (EVINCI) hybrid imaging population

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.

Effect of Coronary Atherosclerosis and Myocardial Ischemia on Plasma Levels of High-Sensitivity Troponin T and NT-proBNP in Patients With Stable Angina.

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.

Registration of myocardial PET and SPECT for viability assessment using mutual information

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.

Chapter 15 Matching Brain–Machine Interface Performance to Space Applications

A brain-machine interface (BMI) is a particular class of human-machine interface (HMI). BMIs have so far been studied mostly as a communication means for people who have little or no voluntary control of muscle activity. For able-bodied users, such as astronauts, a BMI would only be practical if conceived as an augmenting interface. A method is presented for pointing out effective combinations of HMIs and applications of robotics and automation to space. Latency and throughput are selected as performance measures for a hybrid bionic system (HBS), that is, the combination of a user, a device, and a HMI. We classify and briefly describe HMIs and space applications and then compare the performance of classes of interfaces with the requirements of classes of applications, both in terms of latency and throughput. Regions of overlap correspond to effective combinations. Devices requiring simpler control, such as a rover, a robotic camera, or environmental controls are suitable to be driven by means of BMI technology. Free flyers and other devices with six degrees of freedom can be controlled, but only at low-interactivity levels. More demanding applications require conventional interfaces, although they could be controlled by BMIs once the same levels of performance as currently recorded in animal experiments are attained. Robotic arms and manipulators could be the next frontier for noninvasive BMIs. Integrating smart controllers in HBSs could improve interactivity and boost the use of BMI technology in space applications.

Hybrid image visualization tool for 3D integration of CT coronary anatomy and quantitative myocardial perfusion PET

PurposeMultimodal 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.MethodsThe 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.ResultsThe 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.ConclusionsThree-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.

Near infrared image processing to quantitate and visualize oxygen saturation during vascular occlusion

The assessment of microcirculation spatial heterogeneity on the hand skin is the main objective of this work. Near-infrared spectroscopy based 2D imaging is a non-invasive technique for the assessment of tissue oxygenation. The haemoglobin oxygen saturation images were acquired by a dedicated camera (Kent Imaging) during baseline, ischaemia (brachial artery cuff occlusion) and reperfusion. Acquired images underwent a preliminary restoration process aimed at removing degradations occurring during signal capturing. Then, wavelet transform based multiscale analysis was applied to identify edges by detecting local maxima and minima across successive scales. Segmentation of test areas during different conditions was obtained by thresholding-based region growing approach. The method identifies the differences in microcirculatory control of blood flow in different regions of the hand skin. The obtained results demonstrate the potential use of NIRS images for the clinical evaluation of skin disease and microcirculatory dysfunction.