The Integration of Positron Emission Tomography With Magnetic Resonance Imaging

A number of laboratories and companies are currently exploring the development of integrated imaging systems for magnetic resonance imaging (MRI) and positron emission tomography (PET). Scanners for both preclinical and human research applications are being pursued. In contrast to the widely distributed and now quite mature PET/computed tomography technology, most PET/MRI designs allow for simultaneous rather than sequential acquisition of PET and MRI data. While this offers the possibility of novel imaging strategies, it also creates considerable challenges for acquiring artifact-free images from both modalities. This paper discusses the motivation for developing combined PET/MRI technology, outlines the obstacles in realizing such an integrated instrument, and presents recent progress in the development of both the instrumentation and of novel imaging agents for combined PET/MRI studies. The performance of the first-generation PET/MRI systems is described. Finally, a range of possible biomedical applications for PET/MRI are outlined

Investigating biocomplexity through the agent-based paradigm.

Capturing the dynamism that pervades biological systems requires a computational approach that can accommodate both the continuous features of the system environment as well as the flexible and heterogeneous nature of component interactions. This presents a serious challenge for the more traditional mathematical approaches that assume component homogeneity to relate system observables using mathematical equations. While the homogeneity condition does not lead to loss of accuracy while simulating various continua, it fails to offer detailed solutions when applied to systems with dynamically interacting heterogeneous components. As the functionality and architecture of most biological systems is a product of multi-faceted individual interactions at the sub-system level, continuum models rarely offer much beyond qualitative similarity. Agent-based modelling is a class of algorithmic computational approaches that rely on interactions between Turing-complete finite-state machines--or agents--to simulate, from the bottom-up, macroscopic properties of a system. In recognizing the heterogeneity condition, they offer suitable ontologies to the system components being modelled, thereby succeeding where their continuum counterparts tend to struggle. Furthermore, being inherently hierarchical, they are quite amenable to coupling with other computational paradigms. The integration of any agent-based framework with continuum models is arguably the most elegant and precise way of representing biological systems. Although in its nascence, agent-based modelling has been utilized to model biological complexity across a broad range of biological scales (from cells to societies). In this article, we explore the reasons that make agent-based modelling the most precise approach to model biological systems that tend to be non-linear and complex

On-lattice agent-based simulation of populations of cells within the open-source chaste framework

Over the years, agent-based models have been developed that combine cell division and reinforced random walks of cells on a regular lattice, reaction-diffusion equations for nutrients and growth factors and ordinary differential equations (ODEs) for the subcellular networks regulating the cell cycle. When linked to a vascular layer, this multiple scale model framework has been applied to tumour growth and therapy. Here we report on the creation of an agent-based multiscale environment amalgamating the characteristics of these models within a Virtual Pysiological Human (VPH) Exemplar Project. This project enables re-use, integration, expansion and sharing of the model and relevant data. The agent-based and reactiondiffusion parts of the multiscale model have been implemented and are available for download as part of the latest public release of Chaste (“Cancer, Heart and Soft Tissue Environment”), (http://www.cs.ox.ac.uk/chaste/) version 3.1, part of the VPH Toolkit (http://toolkit.vph-noe.eu/). The environment functionalities are verified against the original models, in addition to extra validation of all aspects of the code. In this work, we present the details of the implementation of the agent-based environment, including the system description, the conceptual model, the development of the simulation model and the processes of verification and validation of the simulation results. We explore the potential use of the environment by presenting exemplar applications of the “what if” scenarios that can easily be studied in the environment. These examples relate to tumour growth, cellular competition for resources and tumour responses to hypoxia. We conclude our work by summarising the future steps for the expansion of the current system

Joint fitting reveals hidden interactions in tumor growth

Tumor growth is often the result of the simultaneous development of two or more cancer cell populations. Their interaction between them characterizes the system evolution. To obtain information about these interactions we apply the recently developed vector universality (VUN) formalism to various instances of competition between tumor populations. The formalism allows us: (a) to quantify the growth mechanisms of a HeLa cell colony, describing the phenotype switching responsible for its fast expansion, (b) to reliably reconstruct the evolution of the necrotic and viable fractions in both in vitro and in vivo tumors using data for the time dependences of the total masses, and (c) to show how the shedding of cells leading to subspheroid formation is beneficial to both the spheroid and subspheroid populations, suggesting that shedding is a strong positive influence on cancer dissemination

Targeted therapy in melanoma

Malignant melanoma is a highly lethal disease unless detected early. Single-agent chemotherapy is well tolerated but is associated with very low response rates. Combination chemotherapy and biochemotherapy may improve objective response rates but do not prolong survival and are associated with greater toxicity. Immunotherapeutic approaches such as high-dose interleukin-2 are associated with durable responses in a small percentage of patients, but are impractical for many patients due to accessibility and toxicity issues. Elucidations of the molecular mechanisms of carcinogenesis in melanoma have expanded the horizon of opportunity to alter the natural history of the disease. Multiple signal transduction pathways seem to be aberrant and drugs that target them have been and continue to be in development. In this review we present data on the most promising targeted agents in development, including B-raf inhibitors and other signal transduction inhibitors, oligonucleotides, proteasome inhibitors, as well as inhibitors of angiogenesis. Most agents are in early phase trials although some have already reached phase III evaluation. As knowledge and experience with targeted therapy advance, new challenges appear to be arising particularly in terms of resistance and appropriate patient selection

Automated post-fault diagnosis of power system disturbances

In order to automate the analysis of SCADA and digital fault recorder (DFR) data for a transmission network operator in the UK, the authors have developed an industrial strength multi-agent system entitled protection engineering diagnostic agents (PEDA). The PEDA system integrates a number of legacy intelligent systems for analyzing power system data as autonomous intelligent agents. The integration achieved through multi-agent systems technology enhances the diagnostic support offered to engineers by focusing the analysis on the most pertinent DFR data based on the results of the analysis of SCADA. Since November 2004 the PEDA system has been operating online at a UK utility. In this paper the authors focus on the underlying intelligent system techniques, i.e. rule-based expert systems, model-based reasoning and state-of-the-art multi-agent system technology, that PEDA employs and the lessons learnt through its deployment and online use