RESUMO
Cellular behavior is sustained by genetic programs that are progressively disrupted in pathological conditions--notably, cancer. High-throughput gene expression profiling has been used to infer statistical models describing these cellular programs, and development is now needed to guide orientated modulation of these systems. Here we develop a regression-based model to reverse-engineer a temporal genetic program, based on relevant patterns of gene expression after cell stimulation. This method integrates the temporal dimension of biological rewiring of genetic programs and enables the prediction of the effect of targeted gene disruption at the system level. We tested the performance accuracy of this model on synthetic data before reverse-engineering the response of primary cancer cells to a proliferative (protumorigenic) stimulation in a multistate leukemia biological model (i.e., chronic lymphocytic leukemia). To validate the ability of our method to predict the effects of gene modulation on the global program, we performed an intervention experiment on a targeted gene. Comparison of the predicted and observed gene expression changes demonstrates the possibility of predicting the effects of a perturbation in a gene regulatory network, a first step toward an orientated intervention in a cancer cell genetic program.
Assuntos
Regulação Neoplásica da Expressão Gênica/genética , Redes Reguladoras de Genes/genética , Leucemia Linfoide/genética , Leucemia Linfoide/metabolismo , Modelos Biológicos , Perfilação da Expressão Gênica/métodos , Engenharia Genética/métodos , Ensaios de Triagem em Larga Escala/métodos , Humanos , Análise em Microsséries , Interferência de RNA , Receptores de Antígenos de Linfócitos B/genética , Análise de Regressão , Genética Reversa/métodosRESUMO
Purpose: To compare an investigational device (MEDRAD® Centargo CT Injection System, "Centargo") to the currently available MEDRAD® Stellant CT Injection System ("Stellant"), in terms of efficiency, injector performance, and user satisfaction. Patients and Methods: A total of 425 patients at two sites were enrolled; 198 patients in phase one, a randomized study (98 Stellant and 100 Centargo). The second observational phase included 227 patients who were injected with Centargo. Phase one recorded times for setup, disassembly, and patient changeovers. Demographic data, subjective image quality, and injection parameters were collected. Phase two assessed usability via a questionnaire provided to all end-users of both systems (radiographers). Results: Patient changeover times were statistically significantly faster with Centargo (15.4s ± 8.7s vs 53.7s ± 19.6s, p < 0.001). Centargo day-setup times were similar to Stellant (138.1s ± 92s vs 151.8s ± 30.6s, p = 0.33) and end-of-day-disassembly times were significantly slower (60.6s ± 27s vs 17.1s ± 12.9s, p < 0.001). Based on four different scenarios modelling patient throughput, the projected time savings with Centargo over Stellant was 40-63%, with the highest efficiency improvements for higher throughputs and the use of larger contrast medium bottles. Both Centargo and Stellant usability averaged between "Very Easy" and "Easy" in all responses to the questionnaire. There were no instances of interrupted injections due to communication loss or detected air and no insufficient images due to injector performance. No safety issues were identified. Conclusion: Centargo was able to demonstrate improved efficiency as compared to Stellant while maintaining injector performance and high usability scores.
RESUMO
OBJECTIVE: Over the last decade, rapid technologic evolution in CT has resulted in improved spatial and temporal resolution and acquisition speed, enabling cardiothoracic CT angiography to become a viable and effective noninvasive alternative in the diagnostic algorithm. These new technologic advances have imposed new challenges for the optimization of contrast medium delivery and image acquisition strategies. CONCLUSION: Thorough understanding of contrast medium dynamics is essential for the design of effective acquisition and injection protocols. This article provides an overview of the fundamentals affecting contrast enhancement, emphasizing the modifications to contrast material delivery protocols required to optimize cardiothoracic CT angiography.
Assuntos
Doenças Cardiovasculares/diagnóstico por imagem , Meios de Contraste/administração & dosagem , Angiografia Coronária/métodos , Tomografia Computadorizada por Raios X/métodos , Meios de Contraste/farmacocinética , Humanos , Intensificação de Imagem Radiográfica/métodosRESUMO
OBJECTIVE: Venous air embolism as a complication of contrast media administration from power injection systems in CT is found to occur in 7%-55% of patients, impacting patient safety, diagnostic image quality, workflow efficiency, and patient and radiographer satisfaction. This study reviews the challenges associated with reactive air management approaches employed on contemporary systems, proposes a novel air management approach using proactive methods, and compares the impact of reactive and proactive approaches on injected air volumes under simulated clinical use. METHODS: Injected air volumes from three power injection systems were measured under simulated clinical use via custom air trap fixture. Two of the systems employed reactive air management approaches, while a new system implemented the proposed proactive air management approach. RESULTS: The proactive system injected significantly less air (average of 0.005 mL ± 0.006 mL with a maximum of 0.017 mL) when compared to two systems with reactive approaches (averages of 0.130 mL ± 0.082 mL and 0.106 mL ± 0.094 mL with maximums of 0.259 mL and 0.311 mL, respectively) (p < 0.05). CT images were taken of static and dynamic 0.1 mL air bubbles inside of a vascular phantom, both of which were clearly visible. Additionally, the dynamic bubble was shown to introduce image artifacts similar to those observed clinically. CONCLUSION: Comparison of the injected air volumes show that a system with a proactive air management approach injected significantly less air compared to tested systems employing reactive approaches. SIGNIFICANCE: The results indicate that the use of a proactive approach could significantly reduce the prevalence of observable, and potentially artifact-inducing, venous air embolism in contrast-enhanced CT procedures.
Assuntos
Embolia Aérea , Embolização Terapêutica , Artefatos , Embolia Aérea/diagnóstico por imagem , Embolia Aérea/etiologia , Embolia Aérea/prevenção & controle , Humanos , Imagens de Fantasmas , Tomografia Computadorizada por Raios XRESUMO
During neurosurgical procedures the objective of the neurosurgeon is to achieve the resection of as much diseased tissue as possible while achieving the preservation of healthy brain tissue. The restricted capacity of the conventional operating room to enable the surgeon to visualize critical healthy brain structures and tumor margin has lead, over the past decade, to the development of sophisticated intraoperative imaging techniques to enhance visualization. However, both rigid motion due to patient placement and nonrigid deformations occurring as a consequence of the surgical intervention disrupt the correspondence between preoperative data used to plan surgery and the intraoperative configuration of the patient's brain. Similar challenges are faced in other interventional therapies, such as in cryoablation of the liver, or biopsy of the prostate. We have developed algorithms to model the motion of key anatomical structures and system implementations that enable us to estimate the deformation of the critical anatomy from sequences of volumetric images and to prepare updated fused visualizations of preoperative and intraoperative images at a rate compatible with surgical decision making. This paper reviews the experience at Brigham and Women's Hospital through the process of developing and applying novel algorithms for capturing intraoperative deformations in support of image guided therapy.
Assuntos
Algoritmos , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/cirurgia , Aumento da Imagem/métodos , Interpretação de Imagem Assistida por Computador/métodos , Neurocirurgia/métodos , Técnica de Subtração , Cirurgia Assistida por Computador/métodos , Elasticidade , Humanos , Cuidados Intraoperatórios/métodos , Movimento , Projetos de Pesquisa , UtahRESUMO
A method for constructing a personalized contrast medium protocol at contrast enhanced, Coronary CT Angiography (CCTA) is presented. A one compartment pharmacokinetic model is parameterized and identified with a minimal data set from a test-bolus injection. A direct-search optimization is performed to construct a protocol that achieves target enhancement in the cardiac structures. Clinical results demonstrating the method's ability to achieve prospectively chosen image enhancement levels while reducing contrast medium dose are presented.