Surrogate-driven respiratory motion models relate the motion of the internal anatomy to easily acquired respiratory surrogate signals, such as the motion of the skin surface. They are usually built ...by first using image registration to determine the motion from a number of dynamic images, and then fitting a correspondence model relating the motion to the surrogate signals. In this paper we present a generalized framework that unifies the image registration and correspondence model fitting into a single optimization. This allows the use of 'partial' imaging data, such as individual slices, projections, or k-space data, where it would not be possible to determine the motion from an individual frame of data. Motion compensated image reconstruction can also be incorporated using an iterative approach, so that both the motion and a motion-free image can be estimated from the partial image data. The framework has been applied to real 4DCT, Cine CT, multi-slice CT, and multi-slice MR data, as well as simulated datasets from a computer phantom. This includes the use of a super-resolution reconstruction method for the multi-slice MR data. Good results were obtained for all datasets, including quantitative results for the 4DCT and phantom datasets where the ground truth motion was known or could be estimated.
Vascularisation is a key feature of cancer growth, invasion and metastasis. To better understand the governing biophysical processes and their relative importance, it is instructive to develop ...physiologically representative mathematical models with which to compare to experimental data. Previous studies have successfully applied this approach to test the effect of various biochemical factors on tumour growth and angiogenesis. However, these models do not account for the experimentally observed dependency of angiogenic network evolution on growth-induced solid stresses. This work introduces two novel features: the effects of hapto- and mechanotaxis on vessel sprouting, and mechano-sensitive dynamic vascular remodelling. The proposed three-dimensional, multiscale, in-silico model of dynamically coupled angiogenic tumour growth is specified to in-vivo and in-vitro data, chosen, where possible, to provide a physiologically consistent description. The model is then validated against in-vivo data from murine mammary carcinomas, with particular focus placed on identifying the influence of mechanical factors. Crucially, we find that it is necessary to include hapto- and mechanotaxis to recapitulate observed time-varying spatial distributions of angiogenic vasculature.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Annotation of the recently determined genome sequence of the major dengue vector,
Aedes aegypti, reveals an abundance of detoxification genes. Here, we report the presence of 235 members of the ...cytochrome P450, glutathione transferase and carboxy/cholinesterase families in
Ae. aegypti. This gene count represents an increase of 58% and 36% compared with the fruitfly,
Drosophila melanogaster, and the malaria mosquito,
Anopheles gambiae, respectively. The expansion is not uniform within the gene families. Secure orthologs can be found across the insect species for enzymes that have presumed or proven biosynthetic or housekeeping roles. In contrast, subsets of these gene families that are associated with general xenobiotic detoxification, in particular the CYP6, CYP9 and alpha esterase families, have expanded in
Ae. aegypti. In order to identify detoxification genes associated with resistance to insecticides we constructed an array containing unique oligonucleotide probes for these genes and compared their expression level in insecticide resistant and susceptible strains. Several candidate genes were identified with the majority belonging to two gene families, the CYP9 P450s and the Epsilon GSTs. This ‘
Ae. aegypti Detox Chip’ will facilitate the implementation of insecticide resistance management strategies for arboviral control programmes.
White matter abnormalities on magnetic resonance imaging (MRI) are associated with dementia and include white matter hyperintensities (WMH; also termed leukoaraiosis) and visible perivascular spaces ...(PVS). We review the potential role of impaired drainage of interstitial fluid in the pathogenesis of WMH and PVS. Whereas the volume of extracellular space in the grey matter is tightly controlled, fluid accumulates and expands the extracellular spaces of the white matter in acute hydrocephalus, vasogenic edema and WMH. Although there are no conventional lymphatic vessels in the brain, there is very effective lymphatic drainage for fluid and solutes along restricted pathways in the basement membranes of cerebral capillaries and arteries in young individuals. Lymphatic drainage of the brain is impaired with age and in association with apolipoprotein E ε4, risk factors for Alzheimer's disease and cerebral amyloid angiopathy (CAA). Deposition of proteins in the lymphatic drainage pathways in the walls of cerebral arteries with age is recognized as protein elimination failure angiopathy (PEFA), as in CAA and cerebral autosomal dominant arteriopathy and leukoencephalopathy (CADASIL). Facilitating perivascular lymphatic drainage from the aging brain may play a significant role in the prevention of CAA, WMH and Alzheimer's disease and may enhance the efficacy of immunotherapy for Alzheimer's disease.
Insulin-like growth factor type 1 receptor (IGF-1R) mediates resistance to epidermal growth factor receptor (EGFR) inhibition and may represent a therapeutic target. We conducted a multicenter, ...randomized, double blind, phase II/III trial of dalotuzumab, an anti-IGF-1R monoclonal antibody, with standard therapy in chemo-refractory, KRAS wild-type metastatic colorectal cancer.
Eligible patients were randomly assigned to dalotuzumab 10mg/kg weekly (arm A), dalotuzumab 7.5mg/kg every alternate week (arm B), or placebo (arm C) in combination with cetuximab and irinotecan. Primary endpoints were progression-free survival (PFS) and overall survival (OS). Secondary endpoints included exploratory biomarker analyses. All statistical tests were two-sided.
The trial was prematurely discontinued for futility after 344 eligible KRAS wild-type patients were included in the primary efficacy population (arm A = 116, arm B = 117, arm C = 111). Median PFS was 3.9 months in arm A (hazard ratio HR = 1.33, 95% confidence interval CI = 0.98 to 1.83, P = .07) and 5.4 months in arm B (HR = 1.13, 95% CI = 0.83 to 1.55, P = .44) compared with 5.6 months in arm C. Median OS was 10.8 months in arm A (HR = 1.41, 95% CI = 0.99 to 2.00, P = .06) and 11.6 months in arm B (HR = 1.26, 95% CI = 0.89 to 1.79, P = .18) compared with 14.0 months in arm C. Grade 3 or higher asthenia and hyperglycaemia occurred more frequently with dalotuzumab compared with placebo. In exploratory biomarker analyses, patients with high IGF-1 mRNA tumors in arm A had numerically better PFS (5.6 vs 3.6 months, HR = 0.59, 95% CI = 0.28 to 1.23, P = .16) and OS (17.9 vs 9.4 months, HR = 0.67, 95% CI = 0.31 to 1.45, P = .31) compared with those with high IGF-1 mRNA tumors in arm C. In contrast, in arm C high IGF-1 mRNA expression predicted lower response rate (17.6% vs 37.3%, P = .04), shorter PFS (3.6 vs 6.6 months, HR = 2.15, 95% CI = 1.15 to 4.02, P = .02), and shorter OS (9.4 vs 15.5 months, HR = 2.42, 95% CI = 1.21 to 4.82, P = .01).
Adding dalotuzumab to irinotecan and cetuximab was feasible but did not improve survival outcome. IGF-1R ligands are promising biomarkers for differential response to anti-EGFR and anti-IGF-1R therapies.
Surgical treatment for early-stage breast carcinoma primarily necessitates breast conserving therapy (BCT), where the tumour is removed while preserving the breast shape. To date, there have been ...very few attempts to develop accurate and efficient computational tools that could be used in the clinical environment for pre-operative planning and oncoplastic breast surgery assessment. Moreover, from the breast cancer research perspective, there has been very little effort to model complex mechano-biological processes involved in wound healing. We address this by providing an integrated numerical framework that can simulate the therapeutic effects of BCT over the extended period of treatment and recovery. A validated, three-dimensional, multiscale finite element procedure that simulates breast tissue deformations and physiological wound healing is presented. In the proposed methodology, a partitioned, continuum-based mathematical model for tissue recovery and angiogenesis, and breast tissue deformation is considered. The effectiveness and accuracy of the proposed numerical scheme is illustrated through patient-specific representative examples. Wound repair and contraction numerical analyses of real MRI-derived breast geometries are investigated, and the final predictions of the breast shape are validated against post-operative follow-up optical surface scans from four patients. Mean (standard deviation) breast surface distance errors in millimetres of 3.1 (±3.1), 3.2 (±2.4), 2.8 (±2.7) and 4.1 (±3.3) were obtained, demonstrating the ability of the surgical simulation tool to predict, pre-operatively, the outcome of BCT to clinically useful accuracy.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Methods for detecting and localizing surgical instruments in laparoscopic images are an important element of advanced robotic and computer-assisted interventions. Robotic joint encoders and sensors ...integrated or mounted on the instrument can provide information about the tool's position, but this often has inaccuracy when transferred to the surgeon's point of view. Vision sensors are currently a promising approach for determining the position of instruments in the coordinate frame of the surgical camera. In this study, we propose a vision algorithm for localizing the instrument's pose in 3-D leaving only rotation in the axis of the tool's shaft as an ambiguity. We propose a probabilistic supervised classification method to detect pixels in laparoscopic images that belong to surgical tools. We then use the classifier output to initialize an energy minimization algorithm for estimating the pose of a prior 3-D model of the instrument within a level set framework. We show that the proposed method is robust against noise using simulated data and we perform quantitative validation of the algorithm compared to ground truth obtained using an optical tracker. Finally, we demonstrate the practical application of the technique on in vivo data from minimally invasive surgery with traditional laparoscopic and robotic instruments.
Major scholars in the field, on the basis of a 3-day consensus, created an in-depth review of current knowledge on the role of diet in cardiovascular disease (CVD), the changing global food system ...and global dietary patterns, and potential policy solutions. Evidence from different countries and age/race/ethnicity/socioeconomic groups suggesting the health effects studies of foods, macronutrients, and dietary patterns on CVD appear to be far more consistent though regional knowledge gaps is highlighted. Large gaps in knowledge about the association of macronutrients to CVD in low- and middle-income countries particularly linked with dietary patterns are reviewed. Our understanding of foods and macronutrients in relationship to CVD is broadly clear; however, major gaps exist both in dietary pattern research and ways to change diets and food systems. On the basis of the current evidence, the traditional Mediterranean-type diet, including plant foods and emphasis on plant protein sources provides a well-tested healthy dietary pattern to reduce CVD.
Breast radiology encompasses the full range of imaging modalities from routine imaging via x-ray mammography, magnetic resonance imaging and ultrasound (both two- and three-dimensional), to more ...recent technologies such as digital breast tomosynthesis, and dedicated breast imaging systems for positron emission mammography and ultrasound tomography. In addition new and experimental modalities, such as Photoacoustics, Near Infrared Spectroscopy and Electrical Impedance Tomography etc, are emerging. The breast is a highly deformable structure however, and this greatly complicates visual comparison of imaging modalities for the purposes of breast screening, cancer diagnosis (including image guided biopsy), tumour staging, treatment monitoring, surgical planning and simulation of the effects of surgery and wound healing etc. Due primarily to the challenges posed by these gross, non-rigid deformations, development of automated methods which enable registration, and hence fusion, of information within and across breast imaging modalities, and between the images and the physical space of the breast during interventions, remains an active research field which has yet to translate suitable methods into clinical practice. This review describes current research in the field of breast biomechanical modelling and identifies relevant publications where the resulting models have been incorporated into breast image registration and simulation algorithms. Despite these developments there remain a number of issues that limit clinical application of biomechanical modelling. These include the accuracy of constitutive modelling, implementation of representative boundary conditions, failure to meet clinically acceptable levels of computational cost, challenges associated with automating patient-specific model generation (i.e. robust image segmentation and mesh generation) and the complexity of applying biomechanical modelling methods in routine clinical practice.
PDF
