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The current EU regulatory framework is forcing the need for a substantial and significant reduction of greenhouse gas emissions in all the main economic sectors since climate change effects have been more tangible in recent years. The adoption of actions and measures to reduce CO2 emissions are thus essential for preventing global warming. For this reason, a simplified bottomup approach is presented here to estimate the potential environmental benefit achievable, in terms of CO2 emissions saving, when a set of proposed energy efficiency measures were adopted in relevant economic sectors of the UNESCO area of Vineyard Landscape in Piedmont Region in Italy. Specifically, representative case studies were assumed for each economic sector being studied to identify the energy efficiency measures to be adopted. Then, progressive scenarios with different territorial diffusion of the proposed measures were performed. The analysis shows that a CO2 emission reduction from 7.1% to 32.4% can be potentially obtained by considering different diffusion pathways of the identified energy efficiency measures in the residential, accommodation, private transport, and food industry sectors, so that the UNESCO area can effectively contribute to contrast global warming. The proposed simplified approach can be replicated in other similar context to obtain rough estimation of emission savings due to territorial diffusion of energy efficiency measures considering available regional and local databases. [ABSTRACT FROM AUTHOR]

Cesarone, C. F., L. Scarabelli, I. Demori, S. Balocco, and E. Fugassa. Poly(ADP-ribose) polymerase is affected early by thyroid state during liver regeneration in rats. Am J Physiol Gastrointest Liver Physiol 279: G1219-G1225, 2000.--Poly(ADP-ribose) polymerase (PARP), a nuclear enzyme involved in DNA synthesis, DNA repair, and cell replication and transformation, also plays a role in the early steps of liver regeneration induced by partial hepatectomy (PH). PARP and DNA topoisomerase I (Topo I) activities and de novo DNA synthesis were studied during liver regeneration in rats with altered thyroid state. Hepatic PARP activity, evaluated as [sup.32]P]NAD incorporated into isolated liver nuclei, was inhibited in hyperthyroid rats and increased in hypothyroid animals. In both euthyroid and hyperthyroid rats PARP activity was rapidly stimulated, peaking 6 h after PH. In hypothyroid animals, an early decrease in activity was found, at a minimum of 6 h after PH, followed by an early onset of DNA synthesis. An inverse relationship between PARP and Topo I activities was a shared feature among euthyroid, hypothyroid, and hyperthyroid rats. Together these data show that, in replicating hepatocytes, thyroid hormones exert a regulatory role on PARP activity, which reflects the control of a number of nuclear proteins involved in DNA metabolism. poly(ADP-ribosyl)ation; DNA synthesis; DNA topoisomerase I; partial hepatectomy; liver growth

Vascular tortuosity of supra-aortic vessels is widely considered one of the main reasons for failure and delays in endovascular treatment of large vessel occlusion in patients with acute ischemic stroke. Characterization of tortuosity is a challenging task due to the lack of objective, robust and effective analysis tools. We present a fully automatic method for arterial segmentation, vessel labelling and tortuosity feature extraction applied to the supra-aortic region. A sample of 566 computed tomography angiography scans from acute ischemic stroke patients (aged 74.8 ± 12.9, 51.0% females) were used for training, validation and testing of a segmentation module based on a U-Net architecture (162 cases) and a vessel labelling module powered by a graph U-Net (566 cases). Successively, 30 cases were processed for testing of a tortuosity feature extraction module. Measurements obtained through automatic processing were compared to manual annotations from two observers for a thorough validation of the method. The proposed feature extraction method presented similar performance to the inter-rater variability observed in the measurement of 33 geometrical and morphological features of the arterial anatomy in the supra-aortic region. This system will contribute to the development of more complex models to advance the treatment of stroke by adding immediate automation, objectivity, repeatability and robustness to the vascular tortuosity characterization of patients. [Display omitted] • Vascular tortuosity presents great difficulties for endovascular treatment in stroke. • Fully automatic analysis enables development of applicable tools in clinic. • Validation of feature extraction is key to ensure accurate patient characterization. [ABSTRACT FROM AUTHOR]

Background: Effective breast cancer treatment planning requires balancing tumor control while minimizing radiation exposure to healthy tissues. Choosing between intensity-modulated radiation therapy (IMRT) and three-dimensional conformal radiation therapy (3D-CRT) remains pivotal, influenced by patient anatomy and dosimetric constraints., Purpose: This study aims to develop a decision-making framework utilizing deep learning to predict dose distributions, aiding in the selection of optimal treatment techniques., Methods: A 2D U-Net convolutional neural network (CNN) model was used to predict dose distribution maps and dose-volume histogram (DVH) metrics for breast cancer patients undergoing IMRT and 3D-CRT. The model was trained and fine-tuned using retrospective datasets from two medical centers, accounting for variations in CT systems, dosimetric protocols, and clinical practices, over 346 patients. An additional 30 consecutive patients were selected for external validation, where both 3D-CRT and IMRT plans were manually created. To show the potential of the approach, an independent medical physicist evaluated both dosimetric plans and selected the most appropriate one based on applicable clinical criteria. Confusion matrices were used to compare the decisions of the independent observer with the historical decision and the proposed decision-making framework., Results: Evaluation metrics, including dice similarity coefficients (DSC) and DVH analyses, demonstrated high concordance between predicted and clinical dose distribution for both IMRT and 3D-CRT techniques, especially for organs at risk (OARs). The decision-making framework demonstrated high accuracy (90 % $\%$ ), recall (95.7 % $\%$ ), and precision (91.7 % $\%$ ) when compared to independent clinical evaluations, while the historical decision-making had lower accuracy (50 % $\%$ ), recall (47.8 % $\%$ ), and precision (78.6 % $\%$ )., Conclusions: The proposed decision-making model accurately predicts dose distributions for both 3D-CRT and IMRT, ensuring reliable OAR dose estimation. This decision-making framework significantly outperforms historical decision-making, demonstrating higher accuracy, recall, and precision., (© 2024 The Author(s). Medical Physics published by Wiley Periodicals LLC on behalf of American Association of Physicists in Medicine.)

Background: In mechanical thrombectomy (MT), extracranial vascular tortuosity is among the main determinants of procedure duration and success. Currently, no rapid and reliable method exists to identify the anatomical features precluding fast and stable access to the cervical vessels., Methods: A retrospective sample of 513 patients were included in this study. Patients underwent first-line transfemoral MT following anterior circulation large vessel occlusion stroke. Difficult transfemoral access (DTFA) was defined as impossible common carotid catheterization or time from groin puncture to first carotid angiogram >30 min. A machine learning model based on 29 anatomical features automatically extracted from head-and-neck computed tomography angiography (CTA) was developed to predict DTFA. Three experienced raters independently assessed the likelihood of DTFA on a reduced cohort of 116 cases using a Likert scale as benchmark for the model, using preprocedural CTA as well as automatic 3D vascular segmentation separately., Results: Among the study population, 11.5% of procedures (59/513) presented DTFA. Six different features from the aortic, supra-aortic, and cervical regions were included in the model. Cross-validation resulted in an area under the receiver operating characteristic (AUROC) curve of 0.76 (95% CI 0.75 to 0.76) for DTFA prediction, with high sensitivity for impossible access identification (0.90, 95% CI 0.81 to 0.94). The model outperformed human assessment in the reduced cohort [F1-score (95% CI) by experts with CTA: 0.43 (0.37 to 0.50); experts with 3D segmentation: 0.50 (0.46 to 0.54); and model: 0.70 (0.65 to 0.75)]., Conclusions: A fully automatic model for DTFA prediction was developed and validated. The presented method improved expert assessment of difficult access prediction in stroke MT. Derived information could be used to guide decisions regarding arterial access for MT., Competing Interests: Competing interests: The code used for the present study is stored in the private repository of the Universitat de Barcelona (Barcelona, Spain) (http://diposit.ub.edu/dspace/handle/2445/180158) and is registered for copyright protection on the Safe Creative platform (registry number: 2109279362548) under the title of "ARTERI-AL: an AI framework for stroke operation planning through the automated characterization of vascular tortuosity". AT reports receiving consulting fees from Anaconda Biomed, Balt, Medtronic, MicroVention, Cerus, Merlin Medical, and Stryker. AG-T received consulting fees from Apta Targets. MRi received research funding from Medtronic and Vesalio. MRi declares ownership of Anaconda Biomed and Methinks shares. MRi received consulting fees from Anaconda Biomed, Apta Targets, Medtronic, Stryker, Cerenovus, and Philips., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: This study aims to assess the role and safety of post-dilatation in protected carotid artery stenting (PCAS) using the new MicroNet-covered 2nd-generation stent assessed by cone beam CT scans., Methods: From March 2020 to March 2022, patients were enrolled in the study according to CT angiography results based on the following criteria: Evidence of 70% to 99% carotid stenosis in asymptomatic patients and 50% to 99% in symptomatic patients, per the NASCET index. Using a FilterWire EZ™ (Boston Scientific, Natick, MA, USA) embolic protection system (EPS), MicroNet-covered stent PCAS was performed by two interventional radiologists with at least 8 years of experience in endovascular intervention. Each patient underwent post-dilatation following stent placement. Finally, a third radiologist (not participating in the interventional procedures) evaluated the cone beam CT scans and calculated residual stenosis. Major and minor complications were recorded in the 30 days following the procedure., Results: A total of 192 patients (121 male, mean age 73±10 years) were included in the study, and all patients received post-dilatation following stent implantation. Technical successes were achieved in all procedures. Adverse events noted in this study were limited to periprocedural transient ischemic attacks that occurred in three out of 192 patients (1.6%) and showed a swift complete recovery. The post-dilatation balloon diameters used in the study were: 5.0 mm (30.3%), 5.5 mm (39.3%) and 6 mm (30.3%). Optimized postdilatation resulted in a significant increase in the final luminal area. Similar improvements were observed in all subtypes of plaque., Conclusions: Post-dilatation in protected CAS is safe and induces a significant improvement in the cross-sectional area regardless of the stenotic plaque.

Background: In a recent randomized study, MicroNet-covered stent (CGuard) significantly reduced procedural and post-procedural cerebral embolism in relation to a single-layer CREST study carotid stent, but real-life clinical practice data are limited. The aim is to prospectively assess clinical outcomes of CGuard as a routine revascularization tool for patients with indication to carotid revascularization., Methods: From April 2019 to November 2021, 204 elective patients (age 71.0±7.1years, 69.6% males, 21.7% symptomatic) were enrolled., Results: Mean basal peak-systolic velocity was 251.41±91.85 cm/s with angiographic diameter stenosis 89.7±8.46%. About 34.4% lesions were severely calcified, 6.8% were angulated, and 4.4% showed significant access tortuosity. Access was femoral, with 100% protection device (filter) use. Two hundred and three lesions in 203 patients were treated (1 cross-over to surgery for lack of effective access, no cross-over to other devices); in most cases (66.9%) the stent was placed directly. For pre-dilated lesions, mean balloon diameter was 3.36±0.34mm. Mean nominal stent diameter was 7.64±0.5 mm; length was 37.19±4.5 mm. All stents were post-dilated (balloon diameter 5.2±0.25 mm). Residual stenosis was <30% in all (3.77±6.91%). By discharge, there were 2 minor strokes (0.9%) and one transient ischemic attack. By 30-days, one other minor stroke occurred in relation to de-novo atrial fibrillation. With no deaths or myocardial infarctions, 30-day total death/stroke/myocardial infarction rate was 1.48%. No in-stent thrombosis or patency loss occurred by 30-days. In-stent peak-systolic velocity was 55.49±22.73 cm/s., Conclusions: Thirty-day results from POLGUARD study indicate safety and a low complication rate of the MicroNet-covered carotid stent use in every-day vascular surgery practice of carotid revascularization. Long-term observation is underway.

Purpose: Carotid revascularization can be associated with modifications of the vascular geometry, which may lead to complications. The changes on the vessel angulation before and after a carotid WallStent (WS) implantation are compared against 2 new dual-layer devices, CGuard (CG) and RoadSaver (RS)., Materials and Methods: The study prospectively recruited 217 consecutive patients (112 GC, 73 WS, and 32 RS, respectively). Angiography projections were explored and the one having a higher arterial angle was selected as a basal view. After stent implantation, a stent control angiography was performed selecting the projection having the maximal angle. The same procedure is followed in all the 3 stent types to guarantee comparable conditions. The angulation changes on the stented segments were quantified from both angiographies. The statistical analysis quantitatively compared the pre-and post-angles for the 3 stent types. The results are qualitatively illustrated using boxplots. Finally, the relation between pre- and post-angles measurements is analyzed using linear regression., Results: For CG, no statistical difference in the axial vessel geometry between the basal and postprocedural angles was found. For WS and RS, statistical difference was found between pre- and post-angles. The regression analysis shows that CG induces lower changes from the original curvature with respect to WS and RS., Conclusion: Based on our results, CG determines minor changes over the basal morphology than WS and RS stents. Hence, CG respects better the native vessel anatomy than the other stents.Level of Evidence: Level 4, Case Series.

X-ray crystallography is a powerful method that has significantly contributed to our understanding of the biological function of proteins and other molecules. This method relies on the production of crystals that, however, are usually a bottleneck in the process. For some molecules, no crystallization has been achieved or insufficient crystals were obtained. Some other systems do not crystallize at all, such as nanoparticles which, because of their dimensions, cannot be treated by the usual crystallographic methods. To solve this, whole pair distribution function has been proposed to bridge the gap between Bragg and Debye scattering theories. To execute a fitting, the spectra of several different constructs, composed of millions of particles each, should be computed using a particle-pair or particle-particle (pp) distance algorithm. Using this computation as a test bench for current field-programmable gate array (FPGA) technology, we evaluate how the parallel computation capability of FPGAs can be exploited to reduce the computation time. We present two different solutions to the problem using two state-of-the-art FPGA technologies. In the first one, the main C program uses OmpSs (a high-level programming model developed at the Barcelona Supercomputing Center, that enables task offload to different high-performance computing devices) for task invocation, and kernels are built with OpenCL using reduced data sizes to save transmission time. The second approach uses task and data parallelism to operate on data locally and update data globally in a decoupled task. Benchmarks have been evaluated over an Intel D5005 Programmable Acceleration Card, computing a model of 2 million particles in 81.57 s - 24.5 billion atom pairs per second (bapps)- and over a ZU102 in 115.31 s. In our last test, over an up-to-date Alveo U200 board, the computation lasted for 34.68 s (57.67 bapps). In this study, we analyze the results in relation to the classic terms of speed-up and efficiency and give hints for future improvements focused on reducing the global job time.

Background: This study investigates the dart-throwing motion (DTM) by comparing an inertial measurement unit-based system previously validated for basic motion tasks with an optoelectronic motion capture system. The DTM is interesting as wrist movement during many activities of daily living occur in this movement plane, but the complex movement is difficult to assess clinically., Methods: Ten healthy subjects were recorded while performing the DTM with their right wrist using inertial sensors and skin markers. Maximum range of motion obtained by the different systems and the mean absolute difference were calculated., Results: In the flexion-extension plane, both systems calculated a range of motion of 100° with mean absolute differences of 8°, while in the radial-ulnar deviation plane, a mean absolute difference of 17° and range of motion values of 48° for the optoelectronic system and 59° for the inertial measurement units were found., Conclusions: This study shows the challenge of comparing results of different kinematic motion capture systems for complex movements while also highlighting inertial measurement units as promising for future clinical application in dynamic and coupled wrist movements. Possible sources of error and solutions are discussed.

Background: Total Knee Arthroplasty (TKA) is an intervention that can significantly improve the quality of life of patients with advanced knee osteoarthritis. Early start of rehabilitation and its continuation at home once the patient is discharged are key factors for the success of the process.This study aims to assess the effectiveness of a home-based telerehabilitation solution (ReHub) on improving functional capacity and clinical outcomes for patients who underwent TKA., Methods/design: The study is a randomized, open-label with blinded outcome assessor, parallel assignment clinical trial with a sample size of 52 patients that is conducted according to the SPIRIT recommendations. After the TKA intervention, the patients are randomly allocated to the control group or the experimental group with a 1:1 ratio. Both groups follow a Fast Track recovery protocol which includes discharge after 2-3 days from surgery, a daily plan of 5 exercises for autonomous rehabilitation and domiciliary visits by a physiotherapist starting approximately 2 weeks after surgery. The experimental group uses the sensor-based telerehabilitation system ReHub to perform the exercises. The primary outcome measure is the range of motion of the knee. Secondary outcomes include physical performance, quality of life, pain intensity, muscle strength, treatment adherence and satisfaction with the ReHub system. The outcomes assessment is performed at hospital discharge (baseline), at stitch removal (2 weeks after baseline) and 2 weeks after stitch removal (4 weeks after baseline).The study conforms to the guidelines of the Declaration of Helsinki and was approved by the hospital's ethics committee., Discussion: The study will address an important gap in the evidence base by reporting the effectiveness of an affordable and low-cost home-based telerehabilitation solution in patients who underwent TKA., Ethics and Dissemination: The study was approved by the hospital's ethics committee ("Comité Ético de Investigación Clínica del HCB", reg. HCB/2019/0571). The trial was registred at ClinicalTrials.gov (NCT04155957). The results of this study will be published in peer-reviewed journals as well as national and international conferences., Trial Registration: NCT04155957 (ClinicalTrials.gov)., Highlights: Assessing a home-based telerehabilitation solution effectiveness in knee surgery.In situations such as the CoVid-19 pandemic, it is a resolutive intervention method.Telerehabilitation is an alternative to conventional face-to-face physical therapy.This system is far less demanding in terms of human resources.Range of motion assessment is the primary outcome measure., Competing Interests: MC and AC have a shareholder position at Bio-Sensing Solutions S.L. DR and HM are employees of Bio-Sensing Solutions S.L. but do not have shareholder positions. SB is a member of the scientific advisory board in Bio-Sensing Solutions S.L. The rest of the authors declare no competing interest., (Copyright: © 2021 The Author(s).)

Background: The demand for total hip arthroplasty (THA) is quickly rising given the escalating global incidence of hip osteoarthritis, and it is widely accepted that the post-surgery rehabilitation is key to optimize outcomes. The overall objective of this study is to evaluate the effectiveness of a new telerehabilitation solution, ReHub, for the physical function and clinical outcome improvement following THA. The specific aims of this manuscript are to describe the study design, protocol, content of interventions, and primary and secondary outcomes and to discuss the clinical rehabilitation impact of the expected experimental results., Methods/design: This prospective, randomized, controlled, parallel-group trial will include 56 patients who had undergone primary THA. Patients are randomized to a control group (standard rehabilitation during the 2-week stay in the rehabilitation clinic followed by 3 weeks of unsupervised home-based rehabilitation) or an experimental group (standard rehabilitation during the 2-week stay in the rehabilitation clinic followed by 3 weeks of home-based ReHub-assisted telerehabilitation). The primary outcome is physical performance assessed through the Timed Up-and-Go (TUG) test. Secondary outcomes include independence level, pain intensity, hip disability, hip range of motion, muscle strength, and patient's perception of clinical improvement., Discussion: Proving the clinical and cost-effectiveness of a home-based telerehabilitation program for physical and muscle function following THA could support its systematic incorporation in post-surgical rehabilitation protocols, which should be tailored to the individual and collective needs., Trial Registration: ClinicalTrial.gov NCT04176315 . Registered on 22 November 2019.

An accurate gait characterization is fundamental for diagnosis and treatment in both clinical and sportive fields. Although several devices allow such measurements, the performance comparison between the acquired signals may be a challenging task. A novel pipeline for the accurate non-rigid alignment of gait signals is proposed. In this paper, the measurements of Inertial Measurement Units (IMU) and Optical Motion Capture Systems (OMCAP) are aligned using a modified version of the Dynamic Time Warping (DTW) algorithm. The differences between the two acquisitions are evaluated using both global (RMSE, Correlation Coefficient (CC)) and local (Statistical Parametric Mapping (SPM)) metrics. The method is applied to a data-set obtained measuring the gait of ten healthy subjects walking on a treadmill at three different gait paces. Results show a global bias between the signal acquisition of 0.05°. Regarding the global metrics, a mean RMSE value of 2.65° (0.73°) and an average CC value of 0.99 (0.01) were obtained. The SPM profile shows, in each gait cycle phase, the percentage of cases when two curves are statistically identical and reaches an average of 48% (22%)., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

This study aims to compare a new inertial measurement unit based system with the highly accurate but complex laboratory gold standard, an optoelectronic motion capture system. Inertial measurement units are sensors based on accelerometers, gyroscopes, and/or magnetometers. Ten healthy subjects were recorded while performing flexion-extension and radial-ulnar deviation movements of their right wrist using inertial sensors and skin markers. Maximum range of motion during these trials and mean absolute difference between the systems were calculated. A difference of 10° ± 5° for flexion-extension and 2° ± 1° for radial-ulnar deviation was found between the two systems with absolute range of motion values of 126° and 50° in the respective axes. A Wilcoxon rank sum test resulted in a no statistical differences between the systems with p -values of 0.24 and 0.62. The observed results are even more precise than reports from previous studies, where differences between 14° and 27° for flexion-extension and differences between 6° and 17° for radial-ulnar deviation were found. Effortless and fast applicability, good precision, and low inter-observer variability make inertial measurement unit based systems applicable to clinical settings.

The scratch assay is an in vitro technique used to assess the contribution of molecular and cellular mechanisms to cell migration. The assay can also be used to evaluate therapeutic compounds before clinical use. Current quantification methods of scratch assays deal poorly with irregular cell-free areas and crooked leading edges which are features typically present in the experimental data. We introduce a new migration quantification method, called 'monolayer edge velocimetry', that permits analysis of low-quality experimental data and better statistical classification of migration rates than standard quantification methods. The new method relies on quantifying the horizontal component of the cell monolayer velocity across the leading edge. By performing a classification test on in silico data, we show that the method exhibits significantly lower statistical errors than standard methods. When applied to in vitro data, our method outperforms standard methods by detecting differences in the migration rates between different cell groups that the other methods could not detect. Application of this new method will enable quantification of migration rates from in vitro scratch assay data that cannot be analysed using existing methods.

Purpose: An intraluminal coronary stent is a metal scaffold deployed in a stenotic artery during percutaneous coronary intervention (PCI). In order to have an effective deployment, a stent should be optimally placed with regard to anatomical structures such as bifurcations and stenoses. Intravascular ultrasound (IVUS) is a catheter-based imaging technique generally used for PCI guiding and assessing the correct placement of the stent. A novel approach that automatically detects the boundaries and the position of the stent along the IVUS pullback is presented. Such a technique aims at optimizing the stent deployment., Methods: The method requires the identification of the stable frames of the sequence and the reliable detection of stent struts. Using these data, a measure of likelihood for a frame to contain a stent is computed. Then, a robust binary representation of the presence of the stent in the pullback is obtained applying an iterative and multiscale quantization of the signal to symbols using the Symbolic Aggregate approXimation algorithm., Results: The technique was extensively validated on a set of 103 IVUS of sequences of in vivo coronary arteries containing metallic and bioabsorbable stents acquired through an international multicentric collaboration across five clinical centers. The method was able to detect the stent position with an overall F-measure of 86.4%, a Jaccard index score of 75% and a mean distance of 2.5 mm from manually annotated stent boundaries, and in bioabsorbable stents with an overall F-measure of 88.6%, a Jaccard score of 77.7 and a mean distance of 1.5 mm from manually annotated stent boundaries. Additionally, a map indicating the distance between the lumen and the stent along the pullback is created in order to show the angular sectors of the sequence in which the malapposition is present., Conclusions: Results obtained comparing the automatic results vs the manual annotation of two observers shows that the method approaches the interobserver variability. Similar performances are obtained on both metallic and bioabsorbable stents, showing the flexibility and robustness of the method., (© 2018 American Association of Physicists in Medicine.)

Purpose: An intraluminal coronary stent is a metal mesh tube deployed in a stenotic artery during percutaneous coronary intervention (PCI), in order to prevent acute vessel occlusion. The identification of struts location and the definition of the stent shape is relevant for PCI planning and for patient follow-up. The authors present a fully automatic framework for computer-aided detection (CAD) of intracoronary stents in intravascular ultrasound (IVUS) image sequences. The CAD system is able to detect stent struts and estimate the stent shape., Methods: The proposed CAD uses machine learning to provide a comprehensive interpretation of the local structure of the vessel by means of semantic classification. The output of the classification stage is then used to detect struts and to estimate the stent shape. The proposed approach is validated using a multicentric data-set of 1,015 images from 107 IVUS sequences containing both metallic and bioabsorbable stents., Results: The method was able to detect struts in both metallic stents with an overall F-measure of 77.7% and a mean distance of 0.15 mm from manually annotated struts, and in bioabsorbable stents with an overall F-measure of 77.4% and a mean distance of 0.09 mm from manually annotated struts., Conclusions: The results are close to the interobserver variability and suggest that the system has the potential of being used as a method for aiding percutaneous interventions.

Arterial pulse wave velocity (PWV), an independent predictor of cardiovascular disease, physiologically increases with age; however, growing evidence suggests metabolic syndrome (MetS) accelerates this increase. Magnetic resonance imaging (MRI) enables reliable noninvasive assessment of arterial stiffness by measuring arterial PWV in specific vascular segments. We investigated the association between the presence of MetS and its components with carotid PWV (cPWV) in asymptomatic subjects without diabetes. We assessed cPWV by MRI in 61 individuals (mean age, 55.3 ± 14.1 years; median age, 55 years): 30 with MetS and 31 controls with similar age, sex, body mass index, and LDL-cholesterol levels. The study population was dichotomized by the median age. To remove the physiological association between PWV and age, unpaired t tests and multiple regression analyses were performed using the residuals of the regression between PWV and age. cPWV was higher in middle-aged subjects with MetS than in those without (p = 0.001), but no differences were found in elder subjects (p = 0.313). cPWV was associated with diastolic blood pressure (r = 0.276, p = 0.033) and waist circumference (r = 0.268, p = 0.038). The presence of MetS was associated with increased cPWV regardless of age, sex, blood pressure, and waist (p = 0.007). The MetS components contributing independently to an increased cPWV were hypertension (p = 0.018) and hypertriglyceridemia (p = 0.002). The presence of MetS is associated with an increased cPWV in middle-aged subjects. In particular, hypertension and hypertriglyceridemia may contribute to early progression of carotid stiffness.

Longitudinal kinetics (LOKI) of the arterial wall consists of the shearing motion of the intima-media complex over the adventitia layer in the direction parallel to the blood flow during the cardiac cycle. The aim of this study was to investigate the local variability of LOKI amplitude along the length of the vessel. By use of a previously validated motion-estimation framework, 35 in vivo longitudinal B-mode ultrasound cine loops of healthy common carotid arteries were analyzed. Results indicated that LOKI amplitude is progressively attenuated along the length of the artery, as it is larger in regions located on the proximal side of the image (i.e., toward the heart) and smaller in regions located on the distal side of the image (i.e., toward the head), with an average attenuation coefficient of -2.5 ± 2.0%/mm. Reported for the first time in this study, this phenomenon is likely to be of great importance in improving understanding of atherosclerosis mechanisms, and has the potential to be a novel index of arterial stiffness., (Copyright © 2015 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

This paper describes an evaluation framework that allows a standardized and quantitative comparison of IVUS lumen and media segmentation algorithms. This framework has been introduced at the MICCAI 2011 Computing and Visualization for (Intra)Vascular Imaging (CVII) workshop, comparing the results of eight teams that participated. We describe the available data-base comprising of multi-center, multi-vendor and multi-frequency IVUS datasets, their acquisition, the creation of the reference standard and the evaluation measures. The approaches address segmentation of the lumen, the media, or both borders; semi- or fully-automatic operation; and 2-D vs. 3-D methodology. Three performance measures for quantitative analysis have been proposed. The results of the evaluation indicate that segmentation of the vessel lumen and media is possible with an accuracy that is comparable to manual annotation when semi-automatic methods are used, as well as encouraging results can be obtained also in case of fully-automatic segmentation. The analysis performed in this paper also highlights the challenges in IVUS segmentation that remains to be solved., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Clinical studies on atherosclerosis regression/progression performed by intravascular ultrasound analysis would benefit from accurate alignment of sequences of the same patient before and after clinical interventions and at follow-up. In this article, a methodology for automatic alignment of intravascular ultrasound sequences based on the dynamic time warping technique is proposed. The non-rigid alignment is adapted to the specific task by applying it to multidimensional signals describing the morphologic content of the vessel. Moreover, dynamic time warping is embedded into a framework comprising a strategy to address partial overlapping between acquisitions and a term that regularizes non-physiologic temporal compression/expansion of the sequences. Extensive validation is performed on both synthetic and in vivo data. The proposed method reaches alignment errors of approximately 0.43 mm for pairs of sequences acquired during the same intervention phase and 0.77 mm for pairs of sequences acquired at successive intervention stages., (Copyright © 2013 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

We present a method for automatic struts detection and stent shape estimation in cross-sectional intravascular ultrasound images. A stent shape is first estimated through a comprehensive interpretation of the vessel morphology, performed using a supervised context-aware multi-class classification scheme. Then, the successive strut identification exploits both local appearance and the defined stent shape. The method is tested on 589 images obtained from 80 patients, achieving a F-measure of 74.1% and an averaged distance between manual and automatic struts of 0.10 mm.

Purpose: Atheromatic plaque progression is affected, among others phenomena, by biomechanical, biochemical, and physiological factors. In this paper, the authors introduce a novel framework able to provide both morphological (vessel radius, plaque thickness, and type) and biomechanical (wall shear stress and Von Mises stress) indices of coronary arteries., Methods: First, the approach reconstructs the three-dimensional morphology of the vessel from intravascular ultrasound (IVUS) and Angiographic sequences, requiring minimal user interaction. Then, a computational pipeline allows to automatically assess fluid-dynamic and mechanical indices. Ten coronary arteries are analyzed illustrating the capabilities of the tool and confirming previous technical and clinical observations., Results: The relations between the arterial indices obtained by IVUS measurement and simulations have been quantitatively analyzed along the whole surface of the artery, extending the analysis of the coronary arteries shown in previous state of the art studies. Additionally, for the first time in the literature, the framework allows the computation of the membrane stresses using a simplified mechanical model of the arterial wall., Conclusions: Circumferentially (within a given frame), statistical analysis shows an inverse relation between the wall shear stress and the plaque thickness. At the global level (comparing a frame within the entire vessel), it is observed that heavy plaque accumulations are in general calcified and are located in the areas of the vessel having high wall shear stress. Finally, in their experiments the inverse proportionality between fluid and structural stresses is observed.

We present a fully automatic methodology for the detection of the Media-Adventitia border (MAb) in human coronary artery in Intravascular Ultrasound (IVUS) images. A robust border detection is achieved by means of a holistic interpretation of the detection problem where the target object, i.e. the media layer, is considered as part of the whole vessel in the image and all the relationships between tissues are learnt. A fairly general framework exploiting multi-class tissue characterization as well as contextual information on the morphology and the appearance of the tissues is presented. The methodology is (i) validated through an exhaustive comparison with both Inter-observer variability on two challenging databases and (ii) compared with state-of-the-art methods for the detection of the MAb in IVUS. The obtained averaged values for the mean radial distance and the percentage of area difference are 0.211 mm and 10.1%, respectively. The applicability of the proposed methodology to clinical practice is also discussed., (Copyright © 2012 Elsevier B.V. All rights reserved.)

In this paper, we present a fully automatic method which identifies every bifurcation in an intravascular ultrasound (IVUS) sequence, the corresponding frames, the angular orientation with respect to the IVUS acquisition, and the extension. This goal is reached using a two-level classification scheme: first, a classifier is applied to a set of textural features extracted from each image of a sequence. A comparison among three state-of-the-art discriminative classifiers (AdaBoost, random forest, and support vector machine) is performed to identify the most suitable method for the branching detection task. Second, the results are improved by exploiting contextual information using a multiscale stacked sequential learning scheme. The results are then successively refined using a-priori information about branching dimensions and geometry. The proposed approach provides a robust tool for the quick review of pullback sequences, facilitating the evaluation of the lesion at bifurcation sites. The proposed method reaches an F-Measure score of 86.35%, while the F-Measure scores for inter- and intraobserver variability are 71.63% and 76.18%, respectively. The obtained results are positive. Especially, considering the branching detection task is very challenging, due to high variability in bifurcation dimensions and appearance.

Clinical studies on atherosclerosis regression/progression performed by intravascular ultrasound analysis require the alignment of pullbacks of the same patient before and after clinical interventions, In this paper, a methodology for the automatic alignment of IVUS sequences based on the dynamic time warping technique is proposed. The method is adapted to the specific IVUS alignment task by applying the non-rigid alignment technique to multidimensional morphological signals, and by introducing a sliding window approach together with a regularization term. To show the effectiveness of our method, an extensive validation is performed both on synthetic data and in-vivo IVUS sequences. The proposed method is robust to stent deployment and post dilation surgery and reaches an alignment error of approximately 0.7 mm for in-vivo data, which is comparable to the inter-observer variability.

Speckle noise negatively affects medical ultrasound image shape interpretation and boundary detection. Speckle removal filters are widely used to selectively remove speckle noise without destroying important image features to enhance object boundaries. In this article, a fully automatic bilateral filter tailored to ultrasound images is proposed. The edge preservation property is obtained by embedding noise statistics in the filter framework. Consequently, the filter is able to tackle the multiplicative behavior modulating the smoothing strength with respect to local statistics. The in silico experiments clearly showed that the speckle reducing bilateral filter (SRBF) has superior performances to most of the state of the art filtering methods. The filter is tested on 50 in vivo US images and its influence on a segmentation task is quantified. The results using SRBF filtered data sets show a superior performance to using oriented anisotropic diffusion filtered images. This improvement is due to the adaptive support of SRBF and the embedded noise statistics, yielding a more homogeneous smoothing. SRBF results in a fully automatic, fast and flexible algorithm potentially suitable in wide ranges of speckle noise sizes, for different medical applications (IVUS, B-mode, 3-D matrix array US)., (Copyright 2010 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

Human arteries affected by atherosclerosis are characterized by altered wall viscoelastic properties. The possibility of noninvasively assessing arterial viscoelasticity in vivo would significantly contribute to the early diagnosis and prevention of this disease. This paper presents a noniterative technique to estimate the viscoelastic parameters of a vascular wall Zener model. The approach requires the simultaneous measurement of flow variations and wall displacements, which can be provided by suitable ultrasound Doppler instruments. Viscoelastic parameters are estimated by fitting the theoretical constitutive equations to the experimental measurements using an ARMA parameter approach. The accuracy and sensitivity of the proposed method are tested using reference data generated by numerical simulations of arterial pulsation in which the physiological conditions and the viscoelastic parameters of the model can be suitably varied. The estimated values quantitatively agree with the reference values, showing that the only parameter affected by changing the physiological conditions is viscosity, whose relative error was about 27% even when a poor signal-to-noise ratio is simulated. Finally, the feasibility of the method is illustrated through three measurements made at different flow regimes on a cylindrical vessel phantom, yielding a parameter mean estimation error of 25%.

Purpose: In this article, the authors studied the feasibility of estimating regional mechanical properties in cerebral aneurysms, integrating information extracted from imaging and physiological data with generic computational models of the arterial wall behavior., Methods: A data assimilation framework was developed to incorporate patient-specific geometries into a given biomechanical model, whereas wall motion estimates were obtained from applying registration techniques to a pair of simulated MR images and guided the mechanical parameter estimation. A simple incompressible linear and isotropic Hookean model coupled with computational fluid-dynamics was employed as a first approximation for computational purposes. Additionally, an automatic clustering technique was developed to reduce the number of parameters to assimilate at the optimization stage and it considerably accelerated the convergence of the simulations. Several in silico experiments were designed to assess the influence of aneurysm geometrical characteristics and the accuracy of wall motion estimates on the mechanical property estimates. Hence, the proposed methodology was applied to six real cerebral aneurysms and tested against a varying number of regions with different elasticity, different mesh discretization, imaging resolution, and registration configurations., Results: Several in silico experiments were conducted to investigate the feasibility of the proposed workflow, results found suggesting that the estimation of the mechanical properties was mainly influenced by the image spatial resolution and the chosen registration configuration. According to the in silico experiments, the minimal spatial resolution needed to extract wall pulsation measurements with enough accuracy to guide the proposed data assimilation framework was of 0.1 mm., Conclusions: Current routine imaging modalities do not have such a high spatial resolution and therefore the proposed data assimilation framework cannot currently be used on in vivo data to reliably estimate regional properties in cerebral aneurysms. Besides, it was observed that the incorporation of fluid-structure interaction in a biomechanical model with linear and isotropic material properties did not have a substantial influence in the final results.

Intravascular Ultrasound (IVUS) is an image-guiding technique for cardiovascular diagnostic, providing cross-sectional images of vessels. During the acquisition, the catheter is pulled back (pullback) at a constant speed in order to acquire spatially subsequent images of the artery. However, during this procedure, the heart twist produces a swinging fluctuation of the probe position along the vessel axis. In this paper we propose a real-time gating algorithm based on the analysis of motion blur variations during the IVUS sequence. Quantitative tests performed on an in-vitro ground truth data base shown that our method is superior to state of the art algorithms both in computational speed and accuracy.

A 3D model reproducing the biomechanical behavior of human blood vessels is presented. The model, based on a multilayer geometry composed of right generalized cylinders, enables the representation of different vessel morphologies, including bifurcations, either healthy or affected by stenoses. Using a finite element approach, blood flow is simulated by considering a dynamic displacement of the scatterers (erythrocytes), while arterial pulsation due to the hydraulic pressure is taken into account through a fluid-structure interaction based on a wall model. Each region is acoustically characterized using FIELD II software, which produces the radio frequency echo signals corresponding to echographic scans. Three acoustic physiological phantoms of carotid arteries surrounded by elastic tissue are presented to illustrate the model's capability. The first corresponds to a healthy blood vessel, the second includes a 50% stenosis, and the third represents a carotid bifurcation. Examples of M mode, B mode and color Doppler images derived from these phantoms are shown. Two examples of M-mode image segmentation and the identification of the atherosclerotic plaque boundaries on Doppler color images are reported. The model could be used as a tool for the preliminary evaluation of ultrasound signal processing and visualization techniques.

Weak spots in the aneurysm could be identified estimating the regional stiffness of the wall. Our approach consists in defining a parametric biomechanical model of the vessel which, given the patient's vascular morphology and the blood in- and outflow obtained from non-invasive imaging as well as parameters describing the local elasticity of the wall, enables the computation of the theoretical deformed wall position. The distance between this latter and the one obtained from the aneurysm pulsation is iteratively minimized in order to estimate the optimal set of stiffness parameters. In order to reduce the number of variables to estimate, the aneurysm morphology is clustered into a limited number of regions with uniform stiffness. A random noise perturbation (< 5mm) is applied to the reference deformations and strains, showing that the robustness of the clustering decreases to 75% and errors of the stiffness estimates remain below 10% of the reference values.

Hepatic insulin-like growth factor binding protein (IGFBP) expression is controlled by diverse factors including thyroid hormone, which enhances IGFBP-4 production in hepatocytes. In the present work, we have investigated whether hepatic IGFBP-4 expression is regulated by retinoic acid (RA), which acts via nuclear receptors belonging to the steroid/thyroid hormone receptor superfamily. Primary cultures of adult rat hepatocytes were incubated with two natural stereoisomers of RA, all-trans RA and 9-cis RA (atRA and 9cRA), and with the synthetic RA receptor (RAR)-selective agonist TTNPB. IGFBP-4 mRNA abundance was measured by Northern blot and protein production was evaluated by Ligand blot on hepatocyte-conditioned culture media. Our results indicate that atRA, 9cRA, and TTNPB increase IGFBP-4 expression by cultured hepatocytes, both at the mRNA and protein level. The RARs play a definite role in this regulation, which is independent from ongoing protein synthesis but dependent on active transcription. AtRA and thyroid hormone act synergistically in increasing hepatic IGFBP-4 expression. Our data establish a role for hormonal factors such as thyronines and retinoids in regulating the hepatic IGF system directly at the IGFBP-4 level.

The insulin-like growth factor (IGF) binding proteins (IGFBPs) are important regulators of cell growth produced by different tissues. The IGFBPs regulate cell growth by modulating the activity and bioavailability of IGFs. The evidence that IGFBP-1 is a liver-specific immediate-early gene highly induced after 70% partial hepatectomy (PHx) suggests a role for the IGF-IGFBP system in hepatic regeneration. In this work we analyzed the effect of PHx on the expression of IGFBP-4, which is highly produced by the liver and very abundant in rat serum. Our results show a marked increase in hepatic IGFBP-4 mRNA levels 6-12 h after PHx and no significant change in sham-operated control animals. A parallel rise in IGFBP-4 transcript abundance was observed in the kidneys of PHx rats but not in sham-operated animals. Moreover, ligand blot analysis demonstrated that serum IGFBP-4 levels began to increase 12-24 h after surgery, consistent with the rise in the corresponding mRNA. This enhancement in IGFBP-4 production after PHx could be part of a fine regulatory mechanism to modulate IGF activity during liver regeneration.