Learning patient-specific parameters for a diffuse interface glioblastoma model from neuroimaging data

Parameters in mathematical models for glioblastoma multiforme (GBM) tumour growth are highly patient specific. Here we aim to estimate parameters in a Cahn-Hilliard type diffuse interface model in an optimised way using model order reduction (MOR) based on proper orthogonal decomposition (POD). Based on snapshots derived from finite element simulations for the full order model (FOM) we use POD for dimension reduction and solve the parameter estimation for the reduced order model (ROM). Neuroimaging data are used to define the highly inhomogeneous diffusion tensors as well as to define a target functional in a patient specific manner. The reduced order model heavily relies on the discrete empirical interpolation method (DEIM) which has to be appropriately adapted in order to deal with the highly nonlinear and degenerate parabolic PDEs. A feature of the approach is that we iterate between full order solves with new parameters to compute a POD basis function and sensitivity based parameter estimation for the ROM problems. The algorithm is applied using neuroimaging data for two clinical test cases and we can demonstrate that the reduced order approach drastically decreases the computational effort

Imaging tumour hypoxia with positron emission tomography.

Hypoxia, a hallmark of most solid tumours, is a negative prognostic factor due to its association with an aggressive tumour phenotype and therapeutic resistance. Given its prominent role in oncology, accurate detection of hypoxia is important, as it impacts on prognosis and could influence treatment planning. A variety of approaches have been explored over the years for detecting and monitoring changes in hypoxia in tumours, including biological markers and noninvasive imaging techniques. Positron emission tomography (PET) is the preferred method for imaging tumour hypoxia due to its high specificity and sensitivity to probe physiological processes in vivo, as well as the ability to provide information about intracellular oxygenation levels. This review provides an overview of imaging hypoxia with PET, with an emphasis on the advantages and limitations of the currently available hypoxia radiotracers.Cancer Research UK (CRUK) funded the National Cancer Research Institute (NCRI) PET Research Working party to organise a meeting to discuss imaging cancer with hypoxia tracers and Positron Emission Tomography. IF was funded by CRUK and is also supported by the Chief Scientific Office. ALH is supported by CRUK and the Breast Cancer Research Foundation. RM is funded by NIHR Cambridge Biomedical Research Centre.This is the accepted manuscript. The final version is available from Nature Publishing at http://www.nature.com/bjc/journal/vaop/ncurrent/full/bjc2014610a.html

Molecular imaging of hypoxia with radiolabelled agents

Tissue hypoxia results from an inadequate supply of oxygen (O2) that compromises biological functions. Structural and functional abnormalities of the tumour vasculature together with altered diffusion conditions inside the tumour seem to be the main causes of tumour hypoxia. Evidence from experimental and clinical studies points to a role for tumour hypoxia in tumour propagation, resistance to therapy and malignant progression. This has led to the development of assays for the detection of hypoxia in patients in order to predict outcome and identify patients with a worse prognosis and/or patients that would benefit from appropriate treatments. A variety of invasive and non-invasive approaches have been developed to measure tumour oxygenation including oxygen-sensitive electrodes and hypoxia marker techniques using various labels that can be detected by different methods such as positron emission tomography (PET), single photon emission computed tomography (SPECT), magnetic resonance imaging (MRI), autoradiography and immunohistochemistry. This review aims to give a detailed overview of non-invasive molecular imaging modalities with radiolabelled PET and SPECT tracers that are available to measure tumour hypoxia

Differential effect of spinal cord injury and functional impairment on human brain activation

Reorganization of human brain function after spinal cord injury (SCI) has been shown in electrophysiological studies. However, it is less clear how far changes of brain activation in SCI patients are influenced by the extent of SCI (neuronal lesion) or the consequent functional impairment. Positron emission tomography ([O-15]-H2O-PET) was performed during an unilateral hand movement in SCI patients and healthy subjects. SCI patients with paraplegia and normal hand function were compared to tetraplegic patients with impaired hand movements. Intergroup comparison between paraplegic patients and healthy subjects showed an increased activation of contralateral sensorimotor cortex (SMC), contralateral thalamus, ipsilateral superior parietal lobe, and bilateral cerebellum. In contrast to this, tetraplegic patients with impaired upper limb function revealed only a significant activation of supplementary motor area (SMA). Correlational analysis in the tetraplegic patients showed that the strength of hand movement was related to the activation of contralateral SMC. However, the severity of upper limb sensorimotor deficit was related to a reduced activation of contralateral SMA and ipsilateral cerebellum. The findings suggest that in paraplegic patients with normal hand function the spinal neuronal lesion itself induces a reorganization of brain activation unrelated to upper limb function. Compared to this, in tetraplegic patients changes of brain activation are related to the impaired upper limb function. Therefore, in patients with SCI a differential impact of spinal lesion and functional impairment on brain activation can be shown. The effect of impaired afferent feedback and/or increased compensatory use of non-impaired limbs in SCI patients needs further evaluation

Graphene phosphonic acid as an efficient flame retardant

We report the preparation of graphene phosphonic acid (GPA) via a simple and versatile method and its use as an efficient flame retardant. In order to covalently attach phosphorus to the edges of graphene nanoplatelets, graphite was ball-milled with red phosphorus. The cleavage of graphitic C-C bonds during mechanochemical ball-milling generates reactive carbon species, which react with phosphorus in a sealed ball-mill crusher to form graphene phosphorus. Subsequent opening of the crusher in air moisture leads to violent oxidation of graphene phosphorus into GPA (highest oxidation state). The GPA is readily dispersible in many polar solvents, including neutral water, allowing for solution (spray) coating for high-performance, nontoxic flame-retardant applications.close0