A human neural crest model reveals the developmental impact of neuroblastoma-associated chromosomal aberrations.

Early childhood tumours arise from transformed embryonic cells, which often carry large copy number alterations (CNA). However, it remains unclear how CNAs contribute to embryonic tumourigenesis due to a lack of suitable models. Here we employ female human embryonic stem cell (hESC) differentiation and single-cell transcriptome and epigenome analysis to assess the effects of chromosome 17q/1q gains, which are prevalent in the embryonal tumour neuroblastoma (NB). We show that CNAs impair the specification of trunk neural crest (NC) cells and their sympathoadrenal derivatives, the putative cells-of-origin of NB. This effect is exacerbated upon overexpression of MYCN, whose amplification co-occurs with CNAs in NB. Moreover, CNAs potentiate the pro-tumourigenic effects of MYCN and mutant NC cells resemble NB cells in tumours. These changes correlate with a stepwise aberration of developmental transcription factor networks. Together, our results sketch a mechanistic framework for the CNA-driven initiation of embryonal tumours.

La poesía y sus recursos literarios como metodología cualitativa / Poesia e disposotovos literários como metodologia qualitativa / Poetry and its literary resources as qualitative methodology

Resumen: Este artículo describe las principales contribuciones de la investigación poética (poetic inquiry), como una metodología cualitativa crítica para las ciencias sociales y ciencias de la salud. Así, en primer lugar, se exploran las principales tendencias de investigación asociadas al uso de la poesía como forma narrativa; en un segundo lugar, se analiza el uso de ejercicios concretos para identificar el potencial de la estética narrativa en la construcción de subjetividades alternativas como una forma de reconocer la voz de los participantes de la investigación. En un tercer lugar, se plantea una discusión académica y reflexiva sobre la necesidad de uso de esta metodología en las diferentes universidades y centros de estudio en Latinoamérica. Se puede concluir que la investigación poética es una forma crítica de abordar problemáticas comunitarias a partir de la voz de sus participantes. Asimismo, es una metodología que une a los investigadores y sus participantes en un diálogo generativo, que potencia la investigación cualitativa

Abstract: This article describes the main contributions of poetic inquiry as a critical qualitative methodology for the social sciences and health sciences. Are first explored the present research trends associated with the use of poetry as a narrative construction form; in a second, the use of specific exercises is analyzed to identify the potential of narrative aesthetics in the construction of alternative subjectivities as a way of recognizing the voice of the research participants. Finally, there is an academic and reflective discussion about the need to use this methodology in the different universities and study centers in Latin America. It can be concluded that poetic research is a critical way of approaching community problems based on the voice of its participants. It is also a methodology that unites researchers and their participants in a generative dialogue, which enhances qualitative research

Resumo: Este artigo descreve as principais contribuições da pesquisa poética como uma metodologia qualitativa crítica para ciências sociais e ciências da saúde. Assim, em primeiro lugar, as principais tendências de pesquisa associadas ao uso da poesia como forma narrativa são exploradas; Em segundo lugar, o uso de exercícios específicos é analisado para identificar o potencial da estética narrativa na construção de subjetividades alternativas como forma de reconhecer a voz dos participantes da pesquisa. Em terceiro lugar, há uma discussão acadêmica e reflexiva sobre a necessidade de usar essa metodologia nas diferentes universidades e centros de estudo da América Latina. Pode-se concluir que a pesquisa poética é uma maneira crítica de abordar os problemas da comunidade com base na voz de seus participantes. É também uma metodologia que une pesquisadores e seus participantes em um diálogo generativo, o que melhora a pesquisa qualitativa

Distributing tasks via multiple input pathways increases cellular survival in stress.

Improving in one aspect of a task can undermine performance in another, but how such opposing demands play out in single cells and impact on fitness is mostly unknown. Here we study budding yeast in dynamic environments of hyperosmotic stress and show how the corresponding signalling network increases cellular survival both by assigning the requirements of high response speed and high response accuracy to two separate input pathways and by having these pathways interact to converge on Hog1, a p38 MAP kinase. Cells with only the less accurate, reflex-like pathway are fitter in sudden stress, whereas cells with only the slow, more accurate pathway are fitter in increasing but fluctuating stress. Our results demonstrate that cellular signalling is vulnerable to trade-offs in performance, but that these trade-offs can be mitigated by assigning the opposing tasks to different signalling subnetworks. Such division of labour could function broadly within cellular signal transduction.

Sarcoma histiocítico: presentación de un caso probable / Histiocytic sarcoma: Presentation of a probable case

El sarcoma histiocítico es un desorden de células no Langerhans extremadamente raro con un curso clínico agresivo y limitadas opciones de tratamiento. Se presenta el caso de un paciente adulto joven de género masculino, con cuadro febril prolongado, compromiso hematológico persistente, hepatoesplenomegalia y linfadenopatias generalizadas con curso clínico fatal, en quien por las características clínicas, paraclínicas y de estudios histopatológicos como de inmunohistoquímica se llegó a dicha presunción diagnostica

Histiocytic sarcoma is an extremely rare non-Langerhans cell disorder with an aggressive clinical course and limited options for therapy. We present the case of a young adult male patient, with prolonged fever, persistent hematological involvement, hepatosplenomegaly, and generalized lymphadenopathy with a fatal clinical course, in whom we arrived to this presumptive diagnosis considering the clinical, paraclinical, and histopathological characteristics, as well as immunohistochemistry

Nano Random Forests to mine protein complexes and their relationships in quantitative proteomics data.

Ever-increasing numbers of quantitative proteomics data sets constitute an underexploited resource for investigating protein function. Multiprotein complexes often follow consistent trends in these experiments, which could provide insights about their biology. Yet, as more experiments are considered, a complex's signature may become conditional and less identifiable. Previously we successfully distinguished the general proteomic signature of genuine chromosomal proteins from hitchhikers using the Random Forests (RF) machine learning algorithm. Here we test whether small protein complexes can define distinguishable signatures of their own, despite the assumption that machine learning needs large training sets. We show, with simulated and real proteomics data, that RF can detect small protein complexes and relationships between them. We identify several complexes in quantitative proteomics results of wild-type and knockout mitotic chromosomes. Other proteins covary strongly with these complexes, suggesting novel functional links for later study. Integrating the RF analysis for several complexes reveals known interdependences among kinetochore subunits and a novel dependence between the inner kinetochore and condensin. Ribosomal proteins, although identified, remained independent of kinetochore subcomplexes. Together these results show that this complex-oriented RF (NanoRF) approach can integrate proteomics data to uncover subtle protein relationships. Our NanoRF pipeline is available online.

Inferring time derivatives including cell growth rates using Gaussian processes.

Often the time derivative of a measured variable is of as much interest as the variable itself. For a growing population of biological cells, for example, the population's growth rate is typically more important than its size. Here we introduce a non-parametric method to infer first and second time derivatives as a function of time from time-series data. Our approach is based on Gaussian processes and applies to a wide range of data. In tests, the method is at least as accurate as others, but has several advantages: it estimates errors both in the inference and in any summary statistics, such as lag times, and allows interpolation with the corresponding error estimation. As illustrations, we infer growth rates of microbial cells, the rate of assembly of an amyloid fibril and both the speed and acceleration of two separating spindle pole bodies. Our algorithm should thus be broadly applicable.

Calidad de vida de adolescentes escolarizados de Medellín-Colombia, 2014 / Calidad de vida educados adolescentes Medellin-Colombia, 2014 / Quality of life of adolescent students of Medellin-Colombia, 2014

Objetivo: analizar el perfil de calidad de vida de adolescentes de instituciones educativas públicas de la ciudad de Medellín según factores demográficos, económicos, psicosociales y de salud, 2014. Metodología: evaluación de la calidad de vida de adolescentes de instituciones educativas públicas de Medellín, según funcionalidad familiar, estado de salud y variables sociodemográficas. El estudio es analítico con 3.460 adolescentes seleccionados por muestreo probabilístico. Se utilizaron frecuencias, medidas de resumen, pruebas de hipótesis y regresión lineal. Resultados: el 60,2% son mujeres, 50,7% de estrato bajo, 3,5% ha estado en embarazo, 18,5% sufre alguna enfermedad, 45,5% de las familias son monoparentales, la tercera parte tienen algún grado de disfunción y la escolaridad promedio de los padres se ubica entre 10-11 años. Los puntajes de calidad de vida estuvieron entre 66 y 74 y sus principales factores explicativos fueron funcionalidad familiar, género, estado de salud y zona de residencia. Conclusión: los adolescentes perciben buena calidad de vida; sin embargo, se deben diseñar programas de intervención dirigidos a mejorar aspectos relacionados con la actividad física y salud, estado de ánimo y sentimientos y familia y tiempo libre. En este sentido, se destaca la importancia de la funcionalidad familiar, el género, el estado de salud y la zona de residencia en la percepción de la calidad de vida.

Objective: to analyze the quality of life profile of adolescents from public educational institutions in the city of Medellín based on demographic, economic, psychosocial and health factors, 2014. Methods: this study evaluates the quality of life of adolescents in public educational institutions of Medellin and its association with family functioning, health status and sociodemographic variables. This is an analytical study with 3.460 adolescents selected through probability sampling. Frequencies, summary statistics, hypothesis testing and linear regression were used. Results: 60.2% of the individuals were women, 50.7% from low social classes, 3.5% have been pregnant, 18.5% suffer from some disease, 45.5% of families have single parents, one-third of them have some degree of dysfunction and the average schooling level of the parents is between 10-11 years. The quality of life scores ranged from 66 to 74 and the main explanatory factors were family functioning, gender, health status and area of residence. Conclusion: adolescents perceive good quality of life; however, it is important to design intervention programs to improve aspects related to "physical activity and health", "mood and feelings" and "family and leisure". In this regard, the important role of family functioning, gender, health status and area of residence in the perception of the quality of life is emphasized.

Objetivo: Analisar o perfil da qualidade de vida de adolescentes de instituições de ensino públicas da cidade de Medellín como demográfica, económica, psicossocial e fatores de saúde, 2014. Metodologia: avaliação da qualidade de vida de adolescentes de instituições de ensino públicas de Medellin, como o funcionamento familiar, estado de saúde e as variáveis sociodemográficas. O estudo analítico com 3.460 adolescentes selecionados por amostragem probabilística. foram utilizadas freqüências, medidas de resumo, testes de hipóteses e regressão linear. Resultados : 60,2% são mulheres, 50,7% de baixo estrato, 3,5% ficaram grávidas, 18,5% sofrem de alguma doença, 45,5% das famílias estão monoparentais, um terço têm algum grau de disfunção e escolaridade média dos pais é entre 10-11 anos. O escore de qualidade de vida foram entre 66 e 74 e seus principais fatores estavam familiarizados funcionalidade, sexo, estado de saúde e da área de residência. Conclusão: os adolescentes percebem boa qualidade de vida; no entanto, eles devem ser concebidos programas de intervenção que visem melhorar os aspectos de "atividade física e saúde", "humor e sentimentos" e "tempo para a família". A este respeito, a importância do funcionamento familiar, sexo, estado de saúde e área de residência na percepção da qualidade de vida está.

Proteomics Analysis with a Nano Random Forest Approach Reveals Novel Functional Interactions Regulated by SMC Complexes on Mitotic Chromosomes.

Packaging of DNA into condensed chromosomes during mitosis is essential for the faithful segregation of the genome into daughter nuclei. Although the structure and composition of mitotic chromosomes have been studied for over 30 years, these aspects are yet to be fully elucidated. Here, we used stable isotope labeling with amino acids in cell culture to compare the proteomes of mitotic chromosomes isolated from cell lines harboring conditional knockouts of members of the condensin (SMC2, CAP-H, CAP-D3), cohesin (Scc1/Rad21), and SMC5/6 (SMC5) complexes. Our analysis revealed that these complexes associate with chromosomes independently of each other, with the SMC5/6 complex showing no significant dependence on any other chromosomal proteins during mitosis. To identify subtle relationships between chromosomal proteins, we employed a nano Random Forest (nanoRF) approach to detect protein complexes and the relationships between them. Our nanoRF results suggested that as few as 113 of 5058 detected chromosomal proteins are functionally linked to chromosome structure and segregation. Furthermore, nanoRF data revealed 23 proteins that were not previously suspected to have functional interactions with complexes playing important roles in mitosis. Subsequent small-interfering-RNA-based validation and localization tracking by green fluorescent protein-tagging highlighted novel candidates that might play significant roles in mitotic progression.

Absceso hepático por Klebsiella pneumoniae, asociado con bacteriemia y meningitis. Reporte de un caso / Klebsiella pneumoniae liver abscess associated with bacteremia and meningitis. Case report

El absceso hepático, continúa siendo un importante problema de salud pública. El causado por Klebsiella pneumoniae, se ha descrito en un 29% de los casos en algunas series. Con una mortalidad hasta del 11,3%, se presenta con mayor frecuencia en pacientes con diabetes mellitus, relacionándose con complicaciones a distancia, como meningitis, absceso cerebral y afección pulmonar. Se presenta el caso de un hombre sin factores de riesgo, con síndrome de absceso hepático por Klebsiella pneumoniae con diseminación hematógena dado por la presencia de bacteriemia y meningitis. Fue manejado con cefepime y drenaje percutáneo, presentando mejoría clínica total. La infección por Klebsiella pneumoniae, representa una etiología emergente como causa de abscesos hepáticos con un comportamiento clínico diferente al resto de infecciones relacionadas con este microorganismo...

Liver abscess remains a major public health problem. Some series have reportedKlebsiella pneumoniae as the causative agent of liver abscesses in up to 29% of cases. This condition has a high mortality rate, up to 11.3%, and it occurs more often in patients with diabetes mellitus, being related to disseminated complications such as meningitis, brain abscess, and pulmonary complications. We report the case of a male patient with a liver abscess caused by Klebsiella pneumoniae and no underlying risk factors, associated with hematogenous spread with the occurrence of bacteremia and meningitis. The patient was treated with cefepime and percutaneous drainage, and he completely recovered. Klebsiella pneumoniae infection represents an emerging etiological cause of liver abscesses, with a different clinical behavior compared to other infections related to this microorganism...

Metaanálisis de la percepción de la calidad de vida relacionada con la salud del adolescente según el género / Meta-analysis of the perception of adolescents' health related quality of life by gender / Meta-análise da percepção da qualidade de vida relacionada com a saúde do adolescente segundo o gênero

OBJETIVO: El objetivo del estudio fue metaanalizar, desde el enfoque de género, la CVRS del adolescente según el KIDSREEN -27. METODOLOGIA: revisión sistemática con metaanálisis. Se evaluó reproducibilidad y se realizaron las pruebas Q, Begg, Funel Plot, Galbraith, Influencias, ForestPlot y metaregresión. RESULTADOS : se incluyeron 11 investigaciones con 11.619 adolescentes sanos y enfermos. Los puntajes de "actividad física y salud" y "estado de ánimo y sentimientos" fueron mayores en los hombres; mientras que "apoyo social y amigos" y "entorno escolar" en las mujeres. En la vida familiar y el tiempo libre no hubo diferencias por género. En la metaregresión para sanos y enfermos permanecieron las diferencias para el género masculino. CONCLUSION: se generó evidencia que soporta la necesidad de incluir la perspectiva de género en la planificación, administración de los servicios de salud e identificación de las necesidades asistenciales de adolescentes.

During adolescence, gender differences occur in the perception of health related quality of life (HRQOL). OBJECTIVE: The objective of this study was to meta-analyze, from a gender perspective, the perception that adolescents have of HRQOL according to the KIDSCREEN-27 questionnaire. METHODOLOGY: A systematic review of the literature and a meta-analysis were performed. Reproducibility was assessed and the following tests were performed: Q, Begg, Funel Plot, Galbrait, sensitivity analysis, ForestPlot and meta-regression. RESULTS : the study included 11 investigations with 11.619 healthy and sick adolescents. Scores in "Physical activity and health" and "Mood and feelings" were higher for men; while "Social support and friends" and "School environment" were higher for women. No differences were found between genders in "Family life and leisure".The differences remained for the males In the meta-regression for healthy and sick individuals. CONCLUSION: this study generated scientific evidence supporting the need for a gender perspective in the planning, management of health care services and identification of the health care needs of adolescents.

Durante a adolescência apresentam-se diferenças de gênero na qualidade de vida relacionada com a saúde (CVRS). Objetivo: O objetivo deste estudo foi meta-analisar, desde a abordagem de gênero, a QVRS do adolescente segundo o KIDSCREEN-27. Metodologia: Revisão sistemática com meta-análises.Avaliou-se reprodutibilidade e se realizaram Provas Q, Begg, Funel Plot, Galbraith, Influencias, ForestPlot e meta-regressão. Resultados: Incluíram-se 11 pesquisas com 11.619 adolescentes saudáveis e doentes. As pontuações de "Atividade física e saúde" e "Estado de ânimo e sentimentos" foram maiores nos homens; enquanto que "Apoio social e amigos" e "Entorno escolar"nas mulheres. Na Vida familiar e o tempo livre não houve diferenças por gênero.Na meta-regressão para indivíduos saudáveis e doentes permaneceram as diferenças para o gênero masculino. Conclusão: Gerou-se evidência que suporta a necessidade de incluir a perspectiva de gênero na planificação, administração dos serviços de saúde e identificação das necessidades assistenciais de adolescentes.

Quantitative evaluation for accumulative calibration error and video-CT registration errors in electromagnetic-tracked endoscopy.

PURPOSE: Electromagnetic (EM)-guided endoscopy has demonstrated its value in minimally invasive interventions. Accuracy evaluation of the system is of paramount importance to clinical applications. Previously, a number of researchers have reported the results of calibrating the EM-guided endoscope; however, the accumulated errors of an integrated system, which ultimately reflect intra-operative performance, have not been characterized. To fill this vacancy, we propose a novel system to perform this evaluation and use a 3D metric to reflect the intra-operative procedural accuracy. METHODS: This paper first presents a portable design and a method for calibration of an electromagnetic (EM)-tracked endoscopy system. An evaluation scheme is then described that uses the calibration results and EM-CT registration to enable real-time data fusion between CT and endoscopic video images. We present quantitative evaluation results for estimating the accuracy of this system using eight internal fiducials as the targets on an anatomical phantom: the error is obtained by comparing the positions of these targets in the CT space, EM space and endoscopy image space. To obtain 3D error estimation, the 3D locations of the targets in the endoscopy image space are reconstructed from stereo views of the EM-tracked monocular endoscope. Thus, the accumulated errors are evaluated in a controlled environment, where the ground truth information is present and systematic performance (including the calibration error) can be assessed. RESULTS: We obtain the mean in-plane error to be on the order of 2 pixels. To evaluate the data integration performance for virtual navigation, target video-CT registration error (TRE) is measured as the 3D Euclidean distance between the 3D-reconstructed targets of endoscopy video images and the targets identified in CT. The 3D error (TRE) encapsulates EM-CT registration error, EM-tracking error, fiducial localization error, and optical-EM calibration error. CONCLUSION: We present in this paper our calibration method and a virtual navigation evaluation system for quantifying the overall errors of the intra-operative data integration. We believe this phantom not only offers us good insights to understand the systematic errors encountered in all phases of an EM-tracked endoscopy procedure but also can provide quality control of laboratory experiments for endoscopic procedures before the experiments are transferred from the laboratory to human subjects.

2D/3D registration for X-ray guided bronchoscopy using distance map classification.

In X-ray guided bronchoscopy of peripheral pulmonary lesions, airways and nodules are hardly visible in X-ray images. Transbronchial biopsy of peripheral lesions is often carried out blindly, resulting in degraded diagnostic yield. One solution of this problem is to superimpose the lesions and airways segmented from preoperative 3D CT images onto 2D X-ray images. A feature-based 2D/3D registration method is proposed for the image fusion between the datasets of the two imaging modalities. Two stereo X-ray images are used in the algorithm to improve the accuracy and robustness of the registration. The algorithm extracts the edge features of the bony structures from both CT and X-ray images. The edge points from the X-ray images are categorized into eight groups based on the orientation information of their image gradients. An orientation dependent Euclidean distance map is generated for each group of X-ray feature points. The distance map is then applied to the edge points of the projected CT images whose gradient orientations are compatible with the distance map. The CT and X-ray images are registered by matching the boundaries of the projected CT segmentations to the closest edges of the X-ray images after the orientation constraint is satisfied. Phantom and clinical studies were carried out to validate the algorithm's performance, showing a registration accuracy of 4.19(± 0.5) mm with 48.39(± 9.6) seconds registration time. The algorithm was also evaluated on clinical data, showing promising registration accuracy and robustness.

Antegrade percutaneous closure of membranous ventricular septal defect using X-ray fused with magnetic resonance imaging.

OBJECTIVES: We hypothesized that X-ray fused with magnetic resonance imaging (XFM) roadmaps might permit direct antegrade crossing and delivery of a ventricular septal defect (VSD) closure device and thereby reduce procedure time and radiation exposure. BACKGROUND: Percutaneous device closure of membranous VSD is cumbersome and time-consuming. The procedure requires crossing the defect retrograde, snaring and exteriorizing a guidewire to form an arteriovenous loop, then delivering antegrade a sheath and closure device. METHODS: Magnetic resonance imaging roadmaps of cardiac structures were obtained from miniature swine with spontaneous VSD and registered with live X-ray using external fiducial markers. We compared antegrade XFM-guided VSD crossing with conventional retrograde X-ray-guided crossing for repair. RESULTS: Antegrade XFM crossing was successful in all animals. Compared with retrograde X-ray, antegrade XFM was associated with shorter time to crossing (167 +/- 103 s vs. 284 +/- 61 s; p = 0.025), shorter time to sheath delivery (71 +/- 32 s vs. 366 +/- 145 s; p = 0.001), shorter fluoroscopy time (158 +/- 95 s vs. 390 +/- 137 s; p = 0.003), and reduced radiation dose-area product (2,394 +/- 1,522 mG.m(2) vs. 4,865 +/- 1,759 mG.m(2); p = 0.016). CONCLUSIONS: XFM facilitates antegrade access to membranous VSD from the right ventricle in swine. The simplified procedure is faster and reduces radiation exposure compared with the conventional retrograde approach.

Process integration possibilities for biodiesel production from palm oil using ethanol obtained from lignocellulosic residues of oil palm industry.

In this paper, integration possibilities for production of biodiesel and bioethanol using a single source of biomass as a feedstock (oil palm) were explored through process simulation. The oil extracted from Fresh Fruit Bunches was considered as the feedstock for biodiesel production. An extractive reaction process is proposed for transesterification reaction using in situ produced ethanol, which is obtained from two types of lignocellulosic residues of palm industry (Empty Fruit Bunches and Palm Press Fiber). Several ways of integration were analyzed. The integration of material flows between ethanol and biodiesel production lines allowed a reduction in unit energy costs down to 3.4%, whereas the material and energy integration leaded to 39.8% decrease of those costs. The proposed integrated configuration is an important option when the technology for ethanol production from biomass reaches such a degree of maturity that its production costs be comparable with those of grain or cane ethanol.

A practical global distortion correction method for an image intensifier based x-ray fluoroscopy system.

X-ray images acquired on systems with image intensifiers (II) exhibit characteristic distortion which is due to both external and internal factors. The distortion is dependent on the orientation of the II, a fact particularly relevant to II's mounted on C arms which have several degrees of freedom of motion. Previous descriptions of distortion correction strategies have relied on a dense sampling of the C-arm orientation space, and as such have been limited mostly to a single arc of the primary angle, alpha. We present a new method which smooths the trajectories of the segmented vertices of the grid phantom as a function of a prior to solving the two-dimensional warping problem. It also shows that the same residual errors of distortion correction could be achieved without fitting the trajectories of the grid vertices, but instead applying the previously described global method of distortion correction, followed by directly smoothing the values of the polynomial coefficients as functions of the C-arm orientation parameters. When this technique was applied to a series of test images at arbitrary alpha, the root-mean-square (RMS) residual error was 0.22 pixels. The new method was extended to three degrees of freedom of the C-arm motion: the primary angle, alpha; the secondary angle, beta; and the source-to-intensifier distance, lambda. Only 75 images were used to characterize the distortion for the following ranges: alpha, +/- 45 degrees (Deltaalpha = 22.5 degrees); beta, +/- 36 degrees (Deltabeta = 18 degrees); lambda, 98-118 cm (Deltalambda = 10 cm). When evaluated on a series of test images acquired at arbitrary (alpha, beta, lambda), the RMS residual error was 0.33 pixels. This method is targeted at applications such as guidance of catheter-based interventions and treatment planning for brachytherapy, which require distortion-corrected images over a large range of C-arm orientations.

Technology preview: X-ray fused with magnetic resonance during invasive cardiovascular procedures.

BACKGROUND: We have developed and validated a system for real-time X-ray fused with magnetic resonance imaging, MRI (XFM), to guide catheter procedures with high spatial precision. Our implementation overlays roadmaps-MRI-derived soft-tissue features of interest-onto conventional X-ray fluoroscopy. We report our initial clinical experience applying XFM, using external fiducial markers, electrocardiogram (ECG)- gating, and automated real-time correction for gantry and table movement. METHODS: This prospective case series for technical development was approved by the NHLBI Institutional Review Board and included 19 subjects. Multimodality external fiducial markers were affixed to patients' skin before MRI, which included contrast-enhanced, 3D T1-weighted, or breath-held and ECG-gated 2D steady state free precession imaging at 1.5T. MRI-derived roadmaps were manually segmented while patients were transferred to a calibrated X-ray fluoroscopy system. Image spaces were registered using the fiducial markers and thereafter permitted unrestricted gantry rotation, table panning, and magnification changes. Static and ECG-gated MRI data were transformed from 3D to 2D to correspond with gantry and table position and combined with live X-ray images. RESULTS: Clinical procedures included graft coronary arteriography, right ventricular free-wall biopsy, and iliac and femoral artery recanalization and stenting. MRI roadmaps improved operator confidence, and in the biopsy cases, outperformed the best available alternative imaging modality. Registration errors were increased when external fiducial markers were affixed to more mobile skin positions, such as over the abdomen. CONCLUSION: XFM using external fiducial markers is feasible during X-ray guided catheter treatments. Multimodality image fusion may prove a useful adjunct to invasive cardiovascular procedures.

X-ray fused with magnetic resonance imaging (XFM) to target endomyocardial injections: validation in a swine model of myocardial infarction.

BACKGROUND: Magnetic resonance imaging (MRI) permits 3-dimensional (3D) cardiac imaging with high soft tissue contrast. X-ray fluoroscopy provides high-resolution, 2-dimensional (2D) projection imaging. We have developed real-time x-ray fused with MRI (XFM) to guide invasive procedures that combines the best features of both imaging modalities. We tested the accuracy of XFM using external fiducial markers to guide endomyocardial cell injections in infarcted swine hearts. METHODS AND RESULTS: Endomyocardial injections of iron-labeled mesenchymal stromal cells admixed with tissue dye were performed in previously infarcted hearts of 12 Yucatan miniswine (weight, 33 to 67 kg). Features from cardiac MRI were displayed combined with x-ray in real time to guide injections. During 130 injections, operators were provided with 3D surfaces of endocardium, epicardium, myocardial wall thickness (range, 2.6 to 17.7 mm), and infarct registered with live x-ray images to facilitate device navigation and choice of injection location. XFM-guided injections were compared with postinjection MRI and with necropsy specimens obtained 24 hours later. Visual inspection of the pattern of dye staining on 2,3,5-triphenyltetrazolium chloride-stained heart slices agreed (kappa=0.69) with XFM-derived injection locations mapped onto delayed hyperenhancement MRI and the susceptibility artifacts seen on the postinjection T2*-weighted gradient echo MRI. The distance between the predicted and actual injection locations in vivo was 3.2+/-2.6 mm (n=64), and 75% of injections were within 4.1 mm of the predicted location. CONCLUSIONS: Three-dimensional to two-dimensional registration of x-ray and MR images with the use of external fiducial markers accurately targets endomyocardial injection in a swine model of myocardial infarction.