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1.
Biomaterials ; 311: 122686, 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38971122

RESUMO

Shear stress generated by the flow of blood in the vasculature is a potent regulator of endothelial cell function and vascular structure. While vascular responses to flow are complex and context-dependent, endothelial cell signaling in response to shear stress induced by laminar flows is coordinated by the transcription factor KLF2. The flow-dependent expression of KLF2 in endothelial cells is associated with a quiescent, anti-inflammatory phenotype and has been well characterized in two-dimensional systems but has not been studied in three-dimensional in vitro systems. Here we develop engineered microvascular networks (MVNs) that incorporate a KLF2-based endothelial cell flow sensor within a microfluidic chip, apply continuous flow using an attached microfluidic pump, and study the effects of this flow on vascular structure and function. We found that application of flow to MVNs for 48 h resulted in increased expression of the KLF2 reporter, larger vessel diameters, and decreased vascular branching and resistance. Notably, vessel diameters after the application of flow were independent of initial MVN morphologies. Finally, we found that MVNs exposed to flow have improved vascular barrier function and decreased platelet adhesion. MVNs with KLF2-based flow sensors represent a novel, powerful tool for evaluating the structural and functional effects of flow on engineered three-dimensional vascular systems.

2.
bioRxiv ; 2023 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-37961543

RESUMO

Shear stress generated by the flow of blood in the vasculature is a potent regulator of endothelial cell phenotype and vascular structure. While vascular responses to flow are complex and context-dependent, endothelial cell signaling in response to shear stress induced by laminar flows is coordinated by the transcription factor KLF2. The expression of KLF2 in endothelial cells is associated with a quiescent, anti-inflammatory phenotype and has been well characterized in two-dimensional systems, but has not been studied in three-dimensional in vitro systems. Here we develop engineered microvascular networks (MVNs) with a KLF2-based endothelial cell sensor within a microfluidic chip, apply continuous flow using an attached microfluidic pump, and study the effects of this flow on vascular structure and function. We found that culture of MVNs exposed to flow for 48 hours that resulted in increased expression of the KLF2-GFP-reporter display larger vessel diameters and decreased vascular branching and resistance. Additionally, vessel diameters after the application of flow were independent of initial MVN morphologies. Finally, we found that MVNs exposed to flow have improved vascular barrier function and decreased platelet adhesion. The MVNs with KLF2-based flow sensors represent a powerful tool for evaluating the structural and functional effects of flow on engineered three-dimensional vascular systems.

3.
Eur Radiol ; 33(9): 6557-6568, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37014405

RESUMO

OBJECTIVE: To accurately estimate liver PDFF from chemical shift-encoded (CSE) MRI using a deep learning (DL)-based Multi-Decoder Water-Fat separation Network (MDWF-Net), that operates over complex-valued CSE-MR images with only 3 echoes. METHODS: The proposed MDWF-Net and a U-Net model were independently trained using the first 3 echoes of MRI data from 134 subjects, acquired with conventional 6-echoes abdomen protocol at 1.5 T. Resulting models were then evaluated using unseen CSE-MR images obtained from 14 subjects that were acquired with a 3-echoes CSE-MR pulse sequence with a shorter duration compared to the standard protocol. Resulting PDFF maps were qualitatively assessed by two radiologists, and quantitatively assessed at two corresponding liver ROIs, using Bland Altman and regression analysis for mean values, and ANOVA testing for standard deviation (STD) (significance level: .05). A 6-echo graph cut was considered ground truth. RESULTS: Assessment of radiologists demonstrated that, unlike U-Net, MDWF-Net had a similar quality to the ground truth, despite it considered half of the information. Regarding PDFF mean values at ROIs, MDWF-Net showed a better agreement with ground truth (regression slope = 0.94, R2 = 0.97) than U-Net (regression slope = 0.86, R2 = 0.93). Moreover, ANOVA post hoc analysis of STDs showed a statistical difference between graph cuts and U-Net (p < .05), unlike MDWF-Net (p = .53). CONCLUSION: MDWF-Net showed a liver PDFF accuracy comparable to the reference graph cut method, using only 3 echoes and thus allowing a reduction in the acquisition times. CLINICAL RELEVANCE STATEMENT: We have prospectively validated that the use of a multi-decoder convolutional neural network to estimate liver proton density fat fraction allows a significant reduction in MR scan time by reducing the number of echoes required by 50%. KEY POINTS: • Novel water-fat separation neural network allows for liver PDFF estimation by using multi-echo MR images with a reduced number of echoes. • Prospective single-center validation demonstrated that echo reduction leads to a significant shortening of the scan time, compared to standard 6-echo acquisition. • Qualitative and quantitative performance of the proposed method showed no significant differences in PDFF estimation with respect to the reference technique.


Assuntos
Fígado , Água , Humanos , Estudos Prospectivos , Fígado/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Abdome , Redes Neurais de Computação , Reprodutibilidade dos Testes
4.
J Cardiovasc Transl Res ; 16(4): 862-873, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-36745287

RESUMO

Aortic stenosis is a condition which is fatal if left untreated. Novel quantitative imaging techniques which better characterise transvalvular pressure drops are being developed but require refinement and validation. A customisable and cost-effective workbench valve phantom circuit capable of replicating valve mechanics and pathology was created. The reproducibility and relationship of differing haemodynamic metrics were assessed from ground truth pressure data alongside imaging compatibility. The phantom met the requirements to capture ground truth pressure data alongside ultrasound and magnetic resonance image compatibility. The reproducibility was successfully tested. The robustness of three different pressure drop metrics was assessed: whilst the peak and net pressure drops provide a robust assessment of the stenotic burden in our phantom, the peak-to-peak pressure drop is a metric that is confounded by non-valvular factors such as wave reflection. The peak-to-peak pressure drop is a metric that should be reconsidered in clinical practice. The left panel shows manufacture of low cost, functional valves. The central section demonstrates circuit layout, representative MRI and US images alongside gross valve morphologies. The right panel shows the different pressure drop metrics that were assessed for reproducibility.


Assuntos
Estenose da Valva Aórtica , Valva Aórtica , Humanos , Reprodutibilidade dos Testes , Benchmarking , Hemodinâmica
5.
Am J Physiol Heart Circ Physiol ; 323(2): H285-H300, 2022 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-35714177

RESUMO

The incidence of diastolic dysfunction increases with age in both humans and mice. This is characterized by increased passive stiffness and slower relaxation of the left ventricle. The stiffness arises at least partially from progressively increased interstitial collagen deposition because of highly secretory fibroblasts. In the past, we demonstrated that AMPK activation via the drug 5-aminoimidazole-4-carboxamide riboside (AICAR) in middle-aged mice reduced adverse remodeling after myocardial infarction. Therefore, as an attempt to normalize the fibroblast phenotype, we used 21-mo-old male and female mice and treated them with AICAR (0.166 mg/g body wt) where each mouse was followed in a functional study over a 3-mo period. We found sex-related differences in extracellular matrix (ECM) composition as well as heart function indices at baseline, which were further accentuated by AICAR treatment. AICAR attenuated the age-related increase in left atrial volume (LAV, an indicator of diastolic dysfunction) in female but not in male hearts, which was associated with reduced collagen deposition in the old female heart, and reduced the transcription factor Gli1 expression in cardiac fibroblasts. We further demonstrated that collagen synthesis was dependent on Gli1, which is a target of AMPK-mediated degradation. By contrast, AICAR had a minor impact on cardiac fibroblasts in the old male heart because of blunted AMPK phosphorylation. Hence, it did not significantly improve old male heart function indices. In conclusion, we demonstrated that male and female hearts are phenotypically different, and sex-specific differences need to be considered when analyzing the response to pharmacological intervention.NEW & NOTEWORTHY The aging heart develops diastolic dysfunction because of increased collagen deposition. We attempted to reduce collagen expression in the old heart by activating AMPK using AICAR. An improvement of diastolic function and reduction of cardiac fibrosis was found only in the female heart and correlated with decreased procollagen expression and increased degradation of the transcription factor Gli1. Male hearts display blunted AICAR-dependent AMPK activation and therefore this treatment had no benefits for the male mice.


Assuntos
Proteínas Quinases Ativadas por AMP , Cardiomiopatias , Proteínas Quinases Ativadas por AMP/metabolismo , Envelhecimento/metabolismo , Aminoimidazol Carboxamida/farmacologia , Animais , Colágeno/metabolismo , Feminino , Fibrose , Masculino , Camundongos , Fenótipo , Proteína GLI1 em Dedos de Zinco/genética
7.
Med Image Anal ; 74: 102195, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34419837

RESUMO

While the clinical gold standard for pressure difference measurements is invasive catheterization, 4D Flow MRI is a promising tool for enabling a non-invasive quantification, by linking highly spatially resolved velocity measurements with pressure differences via the incompressible Navier-Stokes equations. In this work we provide a validation and comparison with phantom and clinical patient data of pressure difference maps estimators. We compare the classical Pressure Poisson Estimator (PPE) and the new Stokes Estimator (STE) against catheter pressure measurements under a variety of stenosis severities and flow intensities. Specifically, we use several 4D Flow data sets of realistic aortic phantoms with different anatomic and hemodynamic severities and two patients with aortic coarctation. The phantom data sets are enriched by subsampling to lower resolutions, modification of the segmentation and addition of synthetic noise, in order to study the sensitivity of the pressure difference estimators to these factors. Overall, the STE method yields more accurate results than the PPE method compared to catheterization data. The superiority of the STE becomes more evident at increasing Reynolds numbers with a better capacity of capturing pressure gradients in strongly convective flow regimes. The results indicate an improved robustness of the STE method with respect to variation in lumen segmentation. However, with heuristic removal of the wall-voxels, the PPE can reach a comparable accuracy for lower Reynolds' numbers.


Assuntos
Coartação Aórtica , Velocidade do Fluxo Sanguíneo , Hemodinâmica , Humanos , Imageamento por Ressonância Magnética , Imagens de Fantasmas , Reprodutibilidade dos Testes
9.
Sci Rep ; 11(1): 536, 2021 01 12.
Artigo em Inglês | MEDLINE | ID: mdl-33436716

RESUMO

The maximum value of the first derivative of the invasively measured left ventricular (LV) pressure (+ dP/dtmax or P') is often used to quantify LV contractility, which in mice is limited to a single terminal study. Thus, determination of P' in mouse longitudinal/serial studies requires a group of mice at each desired time point resulting in "pseudo" serial measurements. Alternatively, a noninvasive surrogate for P' will allow for repeated measurements on the same group of mice, thereby minimizing physiological variability and requiring fewer animals. In this study we evaluated aortic acceleration and other parameters of aortic flow velocity as noninvasive indices of LV contractility in mice. We simultaneously measured LV pressure invasively with an intravascular pressure catheter and aortic flow velocity noninvasively with a pulsed Doppler probe in mice, at baseline and after the administration of the positive inotrope, dobutamine. Regression analysis of P' versus peak aortic velocity (vp), peak velocity squared/rise time (vp2/T), peak (+ dvp/dt or v'p) and mean (+ dvm/dt or v'm) aortic acceleration showed a high degree of association (P' versus: vp, r2 = 0.77; vp2/T, r2 = 0.86; v'p, r2 = 0.80; and v'm, r2 = 0.89). The results suggest that mean or peak aortic acceleration or the other parameters may be used as a noninvasive index of LV contractility.


Assuntos
Aorta/fisiologia , Contração Miocárdica/fisiologia , Função Ventricular Esquerda/fisiologia , Aceleração , Animais , Aorta/diagnóstico por imagem , Velocidade do Fluxo Sanguíneo , Dobutamina , Ecocardiografia Doppler de Pulso , Feminino , Masculino , Camundongos Endogâmicos C57BL , Pressão Ventricular
10.
Ageing Res Rev ; 63: 101150, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32846223

RESUMO

The myofibroblast is a specialized fibroblast that expresses α-smooth muscle actin (α-SMA) and participates in wound contraction and fibrosis. The fibroblast to myofibroblast transition depends on chemical and mechanical signals. A fibroblast senses the changes in the environment (extracellular matrix (ECM)) and transduces these changes to the cytoskeleton and the nucleus, resulting in activation or inhibition of α-SMA transcription in a process called mechanosensing. A stiff matrix greatly facilitates the transition from fibroblast to myofibroblast, and although the aging heart is much stiffer than the young one, the aging fibroblast has difficulties in transitioning into the contractile phenotype. This suggests that the events occurring downstream of the matrix, such as activation or changes in expression levels of various proteins participating in mechanotransduction can negatively alter the ability of the aging fibroblast to become a myofibroblast. In this review, we will discuss in detail the changes in ECM, receptors (integrin or non-integrin), focal adhesions, cytoskeleton, and transcription factors involved in mechanosensing that occur with aging.


Assuntos
Fibroblastos , Mecanotransdução Celular , Envelhecimento , Diferenciação Celular , Células Cultivadas , Matriz Extracelular , Humanos , Miofibroblastos
11.
Ann Vasc Surg ; 64: 71-79.e1, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31634593

RESUMO

BACKGROUND: Few series of ruptured abdominal aortic aneurysm (RAAA) from Latin America have been published. OBJECTIVES: To report the outcomes of RAAA treated with open surgical repair (OSR) in a University Hospital in Chile. Secondary objectives are the identification of prognostic factors and survival rates. METHODS: Retrospective review of consecutive RAAA patients treated with OSR between September 1979 and December 2017. Medical records, diagnostic images, and follow-up details were obtained. Statistical methods include multiple logistic regression analysis. RESULTS: One hundred and sixteen patients underwent OSR for RAAA. The average age was 72.3 years (54-95), 62.9% ≥ 70 years, and 81.9% male. Preoperative systolic pressure <90 mm Hg was present in 74 patients (63.8%), and 10 (8.6%) experienced cardiac arrest before surgery. Only 30.2% were known to have an AAA before rupture. The mean aortic diameter was 7.9 cm. Sixteen patients had juxtarenal aneurysms (13.8%). The rupture was intra or retroperitoneal in 111 cases (95.7%), there were 4 fistulas to neighboring veins and one into the duodenum. Reconstruction included tubular graft in 39.7% and bifurcated in 58.6%. The estimated mean blood loss was 3,456 ± 2,768 mL (median 3,000). Mean mechanical ventilation was 7.4 ± 12.0 days and hemodialysis requirement in 21.8%. Six patients died during surgery and other 24 during the first postoperative month or in hospital, for an overall mortality rate of 25.9%. Age ≥70 years (P < 0.01), blood pressure less than 90 mm Hg (P = 0.03) and dialysis (P < 0.01) were associated with higher 30-day mortality rates. The survival rate was 68.0, 65.3, 44.3, and 25.2% at 1, 2, 5, and 10 years, respectively. CONCLUSIONS: EVAR for RAAA is not affordable in every country. Outcomes of open RAAA repair at our institution are similar to results reported recently for OSR by the USA and European Medical centers.


Assuntos
Aneurisma da Aorta Abdominal/cirurgia , Ruptura Aórtica/cirurgia , Procedimentos Cirúrgicos Vasculares , Idoso , Idoso de 80 Anos ou mais , Aneurisma da Aorta Abdominal/diagnóstico por imagem , Aneurisma da Aorta Abdominal/mortalidade , Ruptura Aórtica/diagnóstico por imagem , Ruptura Aórtica/mortalidade , Chile , Feminino , Hospitais Universitários , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/mortalidade , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Procedimentos Cirúrgicos Vasculares/efeitos adversos , Procedimentos Cirúrgicos Vasculares/mortalidade
12.
Am J Case Rep ; 20: 689-696, 2019 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-31086127

RESUMO

BACKGROUND Growth hormone insensitivity and reduced levels of insulin-like growth factor-1 (IGF-1) are associated with metabolic syndrome that includes obesity, hyperglycemia, type 2 diabetes mellitus, and dyslipidemia. Laron syndrome is a rare autosomal recessive condition associated with insensitivity to growth hormone that results in short stature and metabolic syndrome and is usually diagnosed in childhood. This report is of a 42-year-old Mexican woman with untreated growth hormone insensitivity and diabetic retinopathy, in whom gene sequencing supported the identification of a variant of Laron syndrome. CASE REPORT A 42-year-old Mexican woman with untreated growth hormone insensitivity, metabolic syndrome, and type 2 diabetes mellitus was diagnosed with cataracts, severe retinopathy and hearing loss. She was investigated for genetic causes of reduction in IGF-1. Next-generation sequencing (NGS) showed genetic changes in the growth hormone and IGF-1 axis. The patient's phenotype and genetic changes were consistent with Laron syndrome. CONCLUSIONS The early detection of reduced IGF-1 and identification of the cause of growth hormone insensitivity require international consensus on the approach to diagnosis and treatment methods, including effective IGF-1 replacement therapy. Early diagnosis may reduce the clinical consequences of complications that include short stature the development of metabolic syndrome, type 2 diabetes mellitus, and retinopathy.


Assuntos
Retinopatia Diabética/etiologia , Hipersensibilidade a Drogas/etiologia , Hormônio do Crescimento/efeitos adversos , Fator de Crescimento Insulin-Like I/metabolismo , Síndrome de Laron/diagnóstico , Adulto , Retinopatia Diabética/diagnóstico , Hipersensibilidade a Drogas/diagnóstico , Feminino , Humanos , Síndrome de Laron/complicações
13.
Magn Reson Med ; 79(1): 541-553, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28370386

RESUMO

PURPOSE: We propose a 3D finite-element method for the quantification of vorticity and helicity density from 3D cine phase-contrast (PC) MRI. METHODS: By using a 3D finite-element method, we seamlessly estimate velocity gradients in 3D. The robustness and convergence were analyzed using a combined Poiseuille and Lamb-Ossen equation. A computational fluid dynamics simulation was used to compared our method with others available in the literature. Additionally, we computed 3D maps for different 3D cine PC-MRI data sets: phantom without and with coarctation (18 healthy volunteers and 3 patients). RESULTS: We found a good agreement between our method and both the analytical solution of the combined Poiseuille and Lamb-Ossen. The computational fluid dynamics results showed that our method outperforms current approaches to estimate vorticity and helicity values. In the in silico model, we observed that for a tetrahedral element of 2 mm of characteristic length, we underestimated the vorticity in less than 5% with respect to the analytical solution. In patients, we found higher values of helicity density in comparison to healthy volunteers, associated with vortices in the lumen of the vessels. CONCLUSIONS: We proposed a novel method that provides entire 3D vorticity and helicity density maps, avoiding the used of reformatted 2D planes from 3D cine PC-MRI. Magn Reson Med 79:541-553, 2018. © 2017 International Society for Magnetic Resonance in Medicine.


Assuntos
Análise de Elementos Finitos , Processamento de Imagem Assistida por Computador , Imageamento Tridimensional , Imagem Cinética por Ressonância Magnética , Adulto , Algoritmos , Aorta/diagnóstico por imagem , Simulação por Computador , Feminino , Voluntários Saudáveis , Humanos , Hidrodinâmica , Imageamento por Ressonância Magnética , Masculino , Modelos Estatísticos , Imagens de Fantasmas , Software , Viscosidade , Adulto Jovem
14.
Magn Reson Med ; 79(5): 2816-2823, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-28980342

RESUMO

PURPOSE: To decompose the 3D wall shear stress (WSS) vector field into its axial (WSSA ) and circumferential (WSSC ) components using a Laplacian finite element approach. METHODS: We validated our method with in silico experiments involving different geometries and a modified Poiseuille flow. We computed 3D maps of the WSS, WSSA , and WSSC using 4D flow MRI data obtained from 10 volunteers and 10 patients with bicuspid aortic valve (BAV). We compared our method with the centerline method. The mean value, standard deviation, root mean-squared error, and Wilcoxon signed rank test are reported. RESULTS: We obtained an error <0.05% processing analytical geometries. We found good agreement between our method and the modified Poiseuille flow for the WSS, WSSA , and WSSC . We found statistically significance differences between our method and a 3D centerline method. In BAV patients, we found a 220% significant increase in the WSSC in the ascending aorta with respect to volunteers. CONCLUSION: We developed a novel methodology to decompose the WSS vector in WSSA and WSSC in 3D domains, using 4D flow MRI data. Our method provides a more robust quantification of WSSA and WSSC in comparison with other reported methods. Magn Reson Med 79:2816-2823, 2018. © 2017 International Society for Magnetic Resonance in Medicine.


Assuntos
Velocidade do Fluxo Sanguíneo/fisiologia , Imageamento Tridimensional/métodos , Angiografia por Ressonância Magnética/métodos , Adulto , Idoso , Aorta Torácica/diagnóstico por imagem , Aorta Torácica/fisiologia , Feminino , Análise de Elementos Finitos , Humanos , Masculino , Pessoa de Meia-Idade , Imagens de Fantasmas , Estresse Mecânico
15.
Magn Reson Med ; 79(4): 1882-1892, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-28714282

RESUMO

PURPOSE: To assess the variability of peak flow, mean velocity, stroke volume, and wall shear stress measurements derived from 3D cine phase contrast (4D flow) sequences under different conditions of spatial and temporal resolutions. METHODS: We performed controlled experiments using a thoracic aortic phantom. The phantom was connected to a pulsatile flow pump, which simulated nine physiological conditions. For each condition, 4D flow data were acquired with different spatial and temporal resolutions. The 2D cine phase contrast and 4D flow data with the highest available spatio-temporal resolution were considered as a reference for comparison purposes. RESULTS: When comparing 4D flow acquisitions (spatial and temporal resolution of 2.0 × 2.0 × 2.0 mm3 and 40 ms, respectively) with 2D phase-contrast flow acquisitions, the underestimation of peak flow, mean velocity, and stroke volume were 10.5, 10 and 5%, respectively. However, the calculated wall shear stress showed an underestimation larger than 70% for the former acquisition, with respect to 4D flow, with spatial and temporal resolution of 1.0 × 1.0 × 1.0 mm3 and 20 ms, respectively. CONCLUSIONS: Peak flow, mean velocity, and stroke volume from 4D flow data are more sensitive to changes of temporal than spatial resolution, as opposed to wall shear stress, which is more sensitive to changes in spatial resolution. Magn Reson Med 79:1882-1892, 2018. © 2017 International Society for Magnetic Resonance in Medicine.


Assuntos
Aorta Torácica/diagnóstico por imagem , Processamento de Imagem Assistida por Computador/métodos , Imageamento por Ressonância Magnética/métodos , Diástole , Endotélio Vascular/diagnóstico por imagem , Hemodinâmica , Humanos , Aumento da Imagem , Interpretação de Imagem Assistida por Computador , Imageamento Tridimensional , Microscopia de Contraste de Fase , Imagens de Fantasmas , Reprodutibilidade dos Testes , Resistência ao Cisalhamento , Estresse Mecânico , Volume Sistólico , Sístole , Fatores de Tempo
16.
JRSM Cardiovasc Dis ; 6: 2048004017731986, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28975024

RESUMO

OBJECTIVES: To compare the values of pulmonary regurgitation in patients with repaired Tetralogy of Fallot quantified from two-dimensional phase-contrast data, by using a new pixel-wise analysis and the standard velocity-averaging method. DESIGN: Quantitative in silico and in vivo analysis. SETTING: Hospital Sótero del Río. The magnetic resonance images were acquired using a Philips Achieva 1.5T scanner. PARTICIPANTS: Twenty-five patients with repaired Tetralogy of Fallot who underwent cardiovascular magnetic resonance imaging requested by their referring physicians were included in this study. MAIN OUTCOME MEASURES: Using a computational fluid dynamics simulation, we validated our pixel-wise method, quantifying the error of our method in comparison with the standard method. The patients underwent a standard two-dimensional phase-contrast magnetic resonance imaging acquisition for quantifying pulmonary artery flow. Pulmonary regurgitation fraction was estimated by using our pixel-wise and the standard method. The two-dimensional flow profiles were inspected looking for simultaneous antegrade and retrograde flows in the same cardiac phase. Statistical analysis was performed with t-test for related samples, Bland-Altman plots, and Pearson correlation coefficient. RESULTS: Estimation of pulmonary regurgitation fraction using the pixel-wise analysis revealed higher values compared with the standard method (39 ± 16% vs. 30 ± 22%, p-value <0.01). Eight patients (32%) had a difference of more than 10% between methods. Analysis of two-dimensional flow profiles in these patients revealed simultaneous antegrade and retrograde flows through the pulmonary artery during systole-early diastole. CONCLUSION: Quantification of pulmonary regurgitation fraction in patients with repaired Tetralogy of Fallot through a pixel-wise analysis yields higher values of pulmonary regurgitation compared with the standard velocity-averaging method.

17.
Am J Med Sci ; 353(5): 425-432, 2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-28502327

RESUMO

BACKGROUND: Fanconi anemia (FA) is a condition characterized by genetic instability and short stature, which is due to growth hormone (GH) deficiency in most cases. However, no apparent relationships have been identified between FA complementation group genes and GH. In this study, we thereby considered an association between FA and Laron syndrome (LS) (insulin-like growth factor 1 [IGF-1] deficiency). METHODS: A 21-year-old female Mexican patient with a genetic diagnosis of FA was referred to our research department for an evaluation of her short stature. Upon admission to our facility, her phenotype led to a suspicion of LS; accordingly, serum levels of IGF-1 and IGF binding protein 3 were analyzed and a GH stimulation test was performed. In addition, we used a next-generation sequencing approach for a molecular evaluation of FA disease-causing mutations and genes involved in the GH-IGF signaling pathway. RESULTS: Tests revealed low levels of IGF-1 and IGF binding protein 3 that remained within normal ranges, as well as a lack of response to GH stimulation. Sequencing confirmed a defect in the GH receptor signaling pathway. CONCLUSIONS: To the best of our knowledge, this study is the first to suggest an association between FA and LS. We propose that IGF-1 administration might improve some FA complications and functions based upon IGF-1 beneficial actions observed in animal, cell and indirect clinical models: erythropoiesis modulation, immune function improvement and metabolic regulation.


Assuntos
Anemia de Fanconi/complicações , Anemia de Fanconi/genética , Síndrome de Laron/complicações , Síndrome de Laron/genética , Estatura , Feminino , Hormônio do Crescimento Humano/sangue , Humanos , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/sangue , Fator de Crescimento Insulin-Like I/metabolismo , Síndrome de Laron/patologia , México , Receptores da Somatotropina/sangue , Transdução de Sinais , Adulto Jovem
18.
Rev Med Chil ; 145(1): 63-71, 2017 Jan.
Artigo em Espanhol | MEDLINE | ID: mdl-28393971

RESUMO

BACKGROUND: Conventional treatment of deep vein thrombosis (DVT) is anticoagulation, bed rest and limb elevation. Proximal DVT patients with persisting edema, pain and cyanosis of extremities despite of conventional therapy may develop ischemia. Direct treatment of thrombosis becomes necessary. AIM: To report our experience with mechanical trombolysis of proximal lower extremity DVT. MATERIAL AND METHODS: Retrospective review of medical records of proximal DVT patients treated with thrombolysis between March 2012 and August 2015. Thirteen patients, 14 limbs, median age 34 years (22-85), 8 women, were admitted with pain and swelling of recent onset; one patient with venous gangrene. All patients initially received heparin in therapeutic doses without clinical improvement. RESULTS: In all 13 cases, mechanical thrombolysis was performed using AngioJet®, and associated with single dose thrombolytic agent in 9. Additional angioplasty for residual stenosis was performed in 12 (7 stents) and IVCF were implanted in 8. All patients were subsequently anticoagulated. Early outcomes with disappearance of pain and decrease of edema, with no mortality or bleeding complications. The patient with foot gangrene required amputation. CONCLUSIONS: Mechanical thrombolysis with a single dose of a thrombolytic agent is safe and effective in patients with proximal DVT with an unfavorable evolution.


Assuntos
Fibrinolíticos/uso terapêutico , Trombólise Mecânica/métodos , Trombose Venosa/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Angiografia , Feminino , Heparina/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Stents , Resultado do Tratamento , Adulto Jovem
19.
Rev. méd. Chile ; 145(1): 63-71, ene. 2017. ilus, tab
Artigo em Espanhol | LILACS | ID: biblio-845505

RESUMO

Background: Conventional treatment of deep vein thrombosis (DVT) is anticoagulation, bed rest and limb elevation. Proximal DVT patients with persisting edema, pain and cyanosis of extremities despite of conventional therapy may develop ischemia. Direct treatment of thrombosis becomes necessary. Aim: To report our experience with mechanical trombolysis of proximal lower extremity DVT. Material and Methods: Retrospective review of medical records of proximal DVT patients treated with thrombolysis between March 2012 and August 2015. Thirteen patients, 14 limbs, median age 34 years (22-85), 8 women, were admitted with pain and swelling of recent onset; one patient with venous gangrene. All patients initially received heparin in therapeutic doses without clinical improvement. Results: In all 13 cases, mechanical thrombolysis was performed using AngioJet®, and associated with single dose thrombolytic agent in 9. Additional angioplasty for residual stenosis was performed in 12 (7 stents) and IVCF were implanted in 8. All patients were subsequently anticoagulated. Early outcomes with disappearance of pain and decrease of edema, with no mortality or bleeding complications. The patient with foot gangrene required amputation. Conclusions: Mechanical thrombolysis with a single dose of a thrombolytic agent is safe and effective in patients with proximal DVT with an unfavorable evolution.


Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Adulto Jovem , Trombose Venosa/terapia , Trombólise Mecânica/métodos , Fibrinolíticos/uso terapêutico , Angiografia , Heparina/uso terapêutico , Stents , Estudos Retrospectivos , Resultado do Tratamento
20.
Magn Reson Imaging ; 34(7): 1017-25, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27067473

RESUMO

A three-dimensional dual-cardiac-phase (3D-DCP) scan has been proposed to acquire two data sets of the whole heart and great vessels during the end-diastolic and end-systolic cardiac phases in a single free-breathing scan. This method has shown accurate assessment of cardiac anatomy and function but is limited by long acquisition times. This work proposes to accelerate the acquisition and reconstruction of 3D-DCP scans by exploiting redundant information of the outer k-space regions of both cardiac phases. This is achieved using a modified radial-phase-encoding trajectory and gridding reconstruction with uniform coil combination. The end-diastolic acquisition trajectory was angularly shifted with respect to the end-systolic phase. Initially, a fully-sampled 3D-DCP scan was acquired to determine the optimal percentage of the outer k-space data that can be combined between cardiac phases. Thereafter, prospectively undersampled data were reconstructed based on this percentage. As gold standard images, the undersampled data were also reconstructed using iterative SENSE. To validate the method, image quality assessments and a cardiac volume analysis were performed. The proposed method was tested in thirteen healthy volunteers (mean age, 30years). Prospectively undersampled data (R=4) reconstructed with 50% combination led high quality images. There were no significant differences in the image quality and in the cardiac volume analysis between our method and iterative SENSE. In addition, the proposed approach reduced the reconstruction time from 40min to 1min. In conclusion, the proposed method obtains 3D-DCP scans with an image quality comparable to those reconstructed with iterative SENSE, and within a clinically acceptable reconstruction time.


Assuntos
Coração/diagnóstico por imagem , Coração/fisiologia , Processamento de Imagem Assistida por Computador/métodos , Imageamento Tridimensional/métodos , Imageamento por Ressonância Magnética/métodos , Adulto , Algoritmos , Humanos , Estudos Prospectivos , Valores de Referência , Reprodutibilidade dos Testes , Respiração
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