Pedro Castro

A novel automatic algorithm for the segmentation of the lumen of the carotid artery in ultrasound B-mode images

A novel algorithm is proposed for the segmentation of the lumen and bifurcation boundaries of the carotid artery in B-mode ultrasound images. It uses the image contrast characteristics of the lumen and bifurcation of the carotid artery in relation to other tissues and structures for their identification. The relevant ultrasound data regarding the artery presented in the input image is identified using morphologic operators and processed by an anisotropic diffusion filter for speckle noise removal. The information obtained is then used to define two initial contours, one corresponding to the lumen and the other one regarding the bifurcation boundaries, for the application of the Chan-Vese level set segmentation model. A set of longitudinal ultrasound B-mode grayscale images of the common carotid artery was acquired using a GE Healthcare Vivid-e ultrasound system. The results reveal that the new algorithm is effective and robust, and that its main advantage relies on the automatic identification of the carotid lumen, which overcomes the known limitations of the traditional algorithms.

Autonomic dysfunction affects cerebral neurovascular coupling

ObjectiveAutonomic failure (AF) affects the peripheral vascular system, but little is known about its influence on cerebrovascular regulation. Patients with familial amyloidotic polyneuropathy (FAP) were studied as a model for AF.MethodsTen mild (FAPm), 10 severe (FAPs) autonomic dysfunction FAP patients, and 15 healthy controls were monitored in supine and sitting positions for arterial blood pressure (ABP) and heart rate (HR) with arterial volume clamping, and for blood flow velocity (BFV) in posterior (PCA) and contralateral middle cerebral arteries (MCA) with transcranial Doppler. Analysis included resting BFV, cerebrovascular resistance parameters (cerebrovascular resistance index, CVRi; resistance area product, RAP; and critical closing pressure, CrCP), and neurovascular coupling through visually evoked BFV responses in PCA (gain, rate time, attenuation, and natural frequency).ResultsIn non-stimulation conditions, in each position, there were no significant differences between the groups, regarding HR, BP, resting BFV, and vascular resistance parameters. Sitting ABP was higher than in supine in the three groups, although only significantly in controls. Mean BFV was lower in sitting in all the groups, lacking statistical significance only in FAPs PCA. CVRi and CrCP increased with sitting in all the groups, while RAP increased in controls but decreased in FAPm and FAPs. In visual stimulation conditions, FAPs comparing to controls had a significant decrease of natural frequency, in supine and sitting, and of rate time and gain in sitting position.InterpretationThese results demonstrate that cerebrovascular regulation is affected in FAP subjects with AF, and that it worsens with orthostasis.

Oral films as breakthrough tools for oral delivery of proteins/peptides

Therapeutic proteins and peptides demonstrate unique, peerless, pharmacological characteristics such as high specificity to receptors and superior biological mimicking of physiological mechanisms, resulting in a better therapeutic index compared to conventional chemical-derived drugs. However, proteins also present inherent bioavailability limitations. Thus, this paper proposes several effective tools to improve protein/peptide drugs stability, permeability and pharmacokinetics with special emphasis on oral polymeric films as oral delivery platforms. Indeed, oral films present inherent characteristics that can greatly enhance biological performance of proteins and peptides and patient compliance along with other advantages that are critically discussed in this review. A rational choice of excipients addressed in and manufacture processes are also focused. In addition, possible toxicity issues to be overtaken and critical analysis regarding current market tendencies respecting oral films and protein/peptides along with future prospects are disclosed.

Toward hemodynamic diagnosis of carotid artery stenosis based on ultrasound image data and computational modeling

AbstractThe ability of using non-expensive ultrasound (US) image data together with computer fluid simulation to access various severities of carotid stenosis was inquired in this study. Subject-specific hemodynamic conditions were simulated using a developed finite element solver. Individual structured meshing of the common carotid artery (CCA) bifurcation was built from segmented longitudinal and cross-sectional US images; imposed boundary velocities were based on Doppler US measurements. Simulated hemodynamic parameters such as velocities, wall shear stress (WSS) and derived descriptors were able to predict disturbed flow conditions which play an important role in the development of local atherosclerotic plaques. Hemodynamic features from six individual CCA bifurcations were analyzed. High values of time-averaged WSS (TAWSS) were found at stenosis site. Low values of TAWSS were found at the bulb and at the carotid internal and external branches depending on the particular features of each patient. High oscillating shear index and relative residence time values assigned highly disturbed flows at the same artery surface regions that correlate only moderately with low TAWSS results. Based on clinic US examinations, results provide estimates of flow changes and forces at the carotid artery wall toward the link between hemodynamic behavior and stenosis pathophysiology.

Autonomic dysfunction affects dynamic cerebral autoregulation during Valsalva maneuver: comparison between healthy and autonomic dysfunction subjects

The role of autonomic nervous system (ANS) in adapting cerebral blood flow (CBF) to arterial blood pressure (ABP) fluctuations [cerebral autoregulation (CA)] is still controversial. We aimed to study the repercussion of autonomic failure (AF) on dynamic CA during the Valsalva maneuver (VM). Eight AF subjects with familial amyloidotic polineuropahty (FAP) were compared with eight healthy controls. ABP and CBF velocity (CBFV) were measured continuously with Finapres and transcranial Doppler, respectively. Cerebrovascular response was evaluated by cerebrovascular resistance index (CVRi), critical closing pressure (CrCP), and resistance-area product (RAP) changes. Dynamic CA was derived from continuous estimates of autoregulatory index (ARI) [ARI(t)]. During phase II of VM, FAP subjects showed a more pronounced decrease in normalized CBFV (78 ± 19 and 111 ± 16%; P = 0.002), ABP (78 ± 19 and 124 ± 12%; P = 0.0003), and RAP (67 ± 17 and 89 ± 17%; P = 0.019) compared with controls. CrCP and CVRi increased similarly in both groups during strain. ARI(t) showed a biphasic variation in controls with initial increase followed by a decrease during phase II but in FAP this response was blunted (5.4 ± 3.0 and 2.0 ± 2.9; P = 0.033). Our data suggest that dynamic cerebral autoregulatory response is a time-varying phenomena during VM and that it is disturbed by autonomic dysfunction. This study also emphasizes the fact that RAP + CrCP model allowed additional insights into understanding of cerebral hemodynamics, showing a higher vasodilatory response expressed by RAP in AF and an equal CrCP response in both groups during the increased intracranial and intrathoracic pressure, while classical CVRi paradoxically suggests a cerebral vasoconstriction.

How to overcome the limitations of current insulin administration with new non-invasive delivery systems.

Non-invasive insulin delivery systems have potential to overcome the most pressing problem regarding effective treatment of diabetic patients: therapy compliance. To overcome this disadvantage, non-invasive routes such as oral, buccal, pulmonary, nasal and transdermal have been proposed. These new routes of insulin administration may help to suppress hypoglycemia episodes and aid to control weight gain and post-meal glucose. Despite all efforts the invasive route remains preferential, since studies on insulin administration by non-invasive routes conducted to date have not demonstrated clinical efficacy and safety, including some products introduced in the market. Therefore, the aim of this review is to make an update of the current state of administration of insulin by non-invasive routes as alternatives to the conventional invasive route.

Functional Transcranial Doppler: Presymptomatic Changes in Fabry Disease

Background and Aim: Cerebrovascular disease may progress asymptomatically in the early stages of Fabry disease (FD). Our aim was to test whether functional transcranial Doppler (fTCD) could provide useful data in the evaluation of these presymptomatic FD patients. Methods: A cohort of 12 adult FD patients from families with the classical phenotype of the disease was evaluated with fTCD in the posterior cerebral artery. Results: Compared to healthy controls, resting blood velocities were significantly lower in the FD cohort (p = 0.032 for systolic, p = 0.021 for diastolic). FTCD suggested a disturbed neurovascular coupling in the visual cortex of FD patients, with lower gain (p = 0.007) and rate time (p = 0.019). Men had a significantly higher attenuation (p = 0.013) and lower natural frequency (p = 0.046) than the heterozygous women. Conclusion: These data are the first to suggest that patients with FD may develop cortical vascular dysfunction in the territory of the posterior circulation, early in the natural history of the disease. If the present findings are confirmed in larger, prospective studies, fTCD will be useful for assessing stroke risk in as yet asymptomatic FD patients, improving preventive therapeutic management.

Nanoparticles for the delivery of therapeutic antibodies: Dogma or promising strategy?

ABSTRACT Introduction: Over the past two decades, therapeutic antibodies have demonstrated promising results in the treatment of a wide array of diseases. However, the application of antibody-based therapy implies multiple administrations and a high cost of antibody production, resulting in costly therapy. Another disadvantage inherent to antibody-based therapy is the limited stability of antibodies and the low level of tissue penetration. The use of nanoparticles as delivery systems for antibodies allows for a reduction in antibody dosing and may represent a suitable alternative to increase antibody stability Areas covered: We discuss different nanocarriers intended for the delivery of antibodies as well as the corresponding encapsulation methods. Recent developments in antibody nanoencapsulation, particularly the possible toxicity issues that may arise from entrapment of antibodies into nanocarriers, are also assessed. In addition, this review will discuss the alterations in antibody structure and bioactivity that occur with nanoencapsulation. Expert opinion: Nanocarriers can protect antibodies from degradation, ensuring superior bioavailability. Encapsulation of therapeutic antibodies may offer some advantages, including potential targeting, reduced immunogenicity and controlled release. Furthermore, antibody nanoencapsulation may aid in the incorporation of the antibodies into the cells, if intracellular components (e.g. intracellular enzymes, oncogenic proteins, transcription factors) are to be targeted.

Haemodynamic conditions of patient-specific carotid bifurcation based on ultrasound imaging

The purpose of this paper is to complement the characterisation of patient-specific carotid artery bifurcation haemodynamics based on image data obtained by Doppler ultrasound imaging. A methodology for patient-specific 3D luminal surface reconstruction followed by structured hexahedral meshing of the volume and blood flow simulation is presented. Quantitative descriptors of the flow based on wall shear stress (WSS) are used to compare healthy and stenosed carotid bifurcation haemodynamic disturbances. Independently on the presence of stenosis, the internal carotid artery has been identified as a region of abnormal high values of oscillating shear index and relative residence time and low values of time averaged WSS. For the healthy carotid bifurcation, WSS descriptors manage to capture flow disturbances at the external carotid artery. This work addresses the lack of quantitative analysis on anatomically realistic stenosed carotid bifurcations.

Hemorrhagic transformation and cerebral edema in acute ischemic stroke: Link to cerebral autoregulation

BACKGROUND Hemorrhagic transformation and cerebral edema are feared complications of acute ischemic stroke but mechanisms are poorly understood and reliable early markers are lacking. Early assessment of cerebrovascular hemodynamics may advance our knowledge in both areas. We examined the relationship between dynamic cerebral autoregulation (CA) in the early hours post ischemia, and the risk of developing hemorrhagic transformation and cerebral edema at 24h post stroke METHODS: We prospectively enrolled 46 patients from our center with acute ischemic stroke in the middle cerebral artery territory. Cerebrovascular resistance index was calculated. Dynamic CA was assessed by transfer function analysis (coherence, phase and gain) of the spontaneous blood flow velocity and blood pressure oscillations. Infarct volume, hemorrhagic transformation, cerebral edema, and white matter changes were collected from computed tomography performed at presentation and 24h. RESULTS At admission, phase was lower (worse CA) in patients with hemorrhagic transformation [6.6±30 versus 45±38°; adjusted odds ratio 0.95 (95% confidence internal 0.94-0.98), p=0.023] and with cerebral edema [6.6±30 versus 45±38°, adjusted odds ratio 0.96 (0.92-0.999), p=0.044]. Progression to edema was associated with lower cerebrovascular resistance (1.4±0.2 versus 2.3±1.5mmHg/cm/s, p=0.033) and increased cerebral blood flow velocity (51±25 versus 42±17cm/s, p=0.033) at presentation. All hemodynamic differences resolved at 3months CONCLUSIONS: Less effective CA in the early hour post ischemic stroke is associated with increased risk of hemorrhagic transformation and cerebral edema, possibly reflecting breakthrough hyperperfusion and microvascular injury. Early assessment of dynamic CA could be useful in identifying individuals at risk for these complications.