Imaging tumour distribution of a polymeric drug delivery platformin vivoby PET-MRI

Background Over the past decade, molecular imaging has played a key role in the progression of drug delivery platforms from concept to commercialisation. Of the molecular imaging techniques commonly utilised, positron emission tomography (PET) can yield a breadth of information not easily accessible by other methodologies and when combined with other complementary imaging modalities, is a powerful tool for pre- and clinical development of therapeutics. However, very little research has focussed on the information available from complimentary imaging modalities. This paper reports on the data-rich methodologies of contrast enhanced PET/CT and PET/MRI for probing efficacy of polymer drug delivery platforms. Results The information available from an ExiTron nano 6000 contrast enhanced PET/CT and a gadolinium (Gd) enhanced PET/MRI image of a 64Cu labeled HBP in the same mouse was qualitatively compared. Conclusions Gd contrast enhanced PET/MRI offers a powerful methodology for investigating the distribution of polymer drug delivery platforms in vivo and throughout a tumour volume. Furthermore, information about depth of penetration away from primary blood vessels can be gleaned, potentially leading to development of more efficacious delivery vehicles for clinical use.

A follow up MRI-based geometry and computational fluid dynamics study of carotid bifurcation

Cardiovascular disease is the leading causes of death in the developed world. Wall shear stress (WSS) is associated with the initiation and progression of atherogenesis. This study combined the recent advances in MR imaging and computational fluid dynamics (CFD) and evaluated the patient-specific carotid bifurcation. The patient was followed up for 3 years. The geometry changes (tortuosity, curvature, ICA/CCA area ratios, central to the cross-sectional curvature, maximum stenosis) and the CFD factors (Velocity distribute, Wall Shear Stress (WSS) and Oscillatory Shear Index (OSI)) were compared at different time points.The carotid stenosis was a slight increase in the central to the cross-sectional curvature, and it was minor and variable curvature changes for carotid centerline. The OSI distribution presents ahigh-values in the same region where carotid stenosis and normal border, indicating complex flow and recirculation.The significant geometric changes observed during the follow-up may also cause significant changes in bifurcation hemodynamics.

Noninvasive imaging of atheromatous carotid plaques

Atherothrombosis is a systemic disease of the arterial wall that affects the carotid, coronary, and peripheral vascular beds, and the aorta. This condition is associated with complications such as stroke, myocardial infarction, and peripheral vascular disease, which usually result from unstable atheromatous plaques. The study of atheromatous plaques can provide useful information about the natural history and progression of the disease, and aid in the selection of appropriate treatment. Plaque imaging can be crucial in achieving this goal. In this Review, we focus on the various noninvasive imaging techniques that are being used for morphological and functional assessment of carotid atheromatous plaques in the clinical setting.

In vivo non-invasive high resolution MR-based method for the determination of the elastic modulus of arterial vessels

The mechanical properties of arterial walls have long been recognized to play an essential role in the development and progression of cardiovascular disease (CVD). Early detection of variations in the elastic modulus of arteries would help in monitoring patients at high cardiovascular risk stratifying them according to risk. An in vivo, non-invasive, high resolution MR-phase-contrast based method for the estimation of the time-dependent elastic modulus of healthy arteries was developed, validated in vitro by means of a thin walled silicon rubber tube integrated into an existing MR-compatible flow simulator and used on healthy volunteers. A comparison of the elastic modulus of the silicon tube measured from the MRI-based technique with direct measurements confirmed the method's capability. The repeatability of the method was assessed. Viscoelastic and inertial effects characterizing the dynamic response of arteries in vivo emerged from the comparison of the pressure waveform and the area variation curve over a period. For all the volunteers who took part in the study the elastic modulus was found to be in the range 50-250 kPa, to increase during the rising part of the cycle, and to decrease with decreasing pressure during the downstroke of systole and subsequent diastole.

Effects of the sensorimotor training volume on sensorimotor function in patients following lower limb arthroplasty

Background Sensorimotor function is degraded in patients after lower limb arthroplasty. Sensorimotor training is thought to improve sensorimotor skills, however, the optimal training stimulus with regard to volume, frequency, duration, and intensity is still unknown. The aim of this study, therefore, was to firstly quantify the progression of sensorimotor function after total hip (THA) or knee (TKA) arthroplasty and, as second step, to evaluate effects of different sensorimotor training volumes. Methods 58 in-patients during their rehabilitation after THA or TKA participated in this prospective cohort study. Sensorimotor function was assessed using a test battery including measures of stabilization capacity, static balance, proprioception, and gait, along with a self-reported pain and function. All participants were randomly assigned to one of three intervention groups performing sensorimotor training two, four, or six times per week. Outcome measures were taken at three instances, at baseline (pre), after 1.5 weeks (mid) and at the conclusion of the 3 week program (post). Results All measurements showed significant improvements over time, with the exception of proprioception and static balance during quiet bipedal stance which showed no significant main effects for time or intervention. There was no significant effect of sensorimotor training volume on any of the outcome measures. Conclusion We were able to quantify improvements in measures of dynamic, but not static, sensorimotor function during the initial three weeks of rehabilitation following TKA/THA. Although sensorimotor improvements were independent of the training volume applied in the current study, long-term effects of sensorimotor training volume need to be investigated to optimize training stimulus recommendations.

Osteopenia and rickets in the extremely low birth weight infant: A survey of the incidence and a radiological classification

A review was carried out of the radiographs of twenty-five infants with birth weights under 1000 G, who survived for more than twenty-eight days; eighteen of these had enough suitable films for a survey of the progressive bone changes which occur in these infants, including estimation of humeral cortical cross-sectional area. The incidence of the changes has been assessed and a typical progression of radiographic appearances has been shown, with a suggested system of staging. All infants showed some loss of bone mineral, with frank changes of rickets occurring in forty-four percent. Aetiological factors are mainly concerned with the difficulty of supplying and ensuring absorption of sufficient bone mineral (calcium and phosphate) and vitamin D. Liver immaturity may be another factor. Disease states additional to prematurity accentuate the problem. Rib fractures occurring around 80–90 days post-nataEy commonly draw attention to the bone disorder and are probably the major clinical factor of importance; there is a high incidence of associated lung disease of uncertain pathology. Attention is drawn to possible confusion with other bone disorders in the post-natal period.

Monitoring healing progression and characterizing the mechanical environment in preclinical models for bone tissue engineering

The treatment of large segmental bone defects remains a significant clinical challenge. Due to limitations surrounding the use of bone grafts, tissue-engineered constructs for the repair of large bone defects could offer an alternative. Before translation of any newly developed tissue engineering (TE) approach to the clinic, efficacy of the treatment must be shown in a validated preclinical large animal model. Currently, biomechanical testing, histology, and microcomputed tomography are performed to assess the quality and quantity of the regenerated bone. However, in vivo monitoring of the progression of healing is seldom performed, which could reveal important information regarding time to restoration of mechanical function and acceleration of regeneration. Furthermore, since the mechanical environment is known to influence bone regeneration, and limb loading of the animals can poorly be controlled, characterizing activity and load history could provide the ability to explain variability in the acquired data sets and potentially outliers based on abnormal loading. Many approaches have been devised to monitor the progression of healing and characterize the mechanical environment in fracture healing studies. In this article, we review previous methods and share results of recent work of our group toward developing and implementing a comprehensive biomechanical monitoring system to study bone regeneration in preclinical TE studies.

Inflammation-driven bone formation in a mouse model of ankylosing spondylitis: Sequential not parallel processes

Background Ankylosing spondylitis (AS) is an immune-mediated arthritis particularly targeting the spine and pelvis and is characterised by inflammation, osteoproliferation and frequently ankylosis. Current treatments that predominately target inflammatory pathways have disappointing efficacy in slowing disease progression. Thus, a better understanding of the causal association and pathological progression from inflammation to bone formation, particularly whether inflammation directly initiates osteoproliferation, is required. Methods The proteoglycan-induced spondylitis (PGISp) mouse model of AS was used to histopathologically map the progressive axial disease events, assess molecular changes during disease progression and define disease progression using unbiased clustering of semi-quantitative histology. PGISp mice were followed over a 24-week time course. Spinal disease was assessed using a novel semi-quantitative histological scoring system that independently evaluated the breadth of pathological features associated with PGISp axial disease, including inflammation, joint destruction and excessive tissue formation (osteoproliferation). Matrix components were identified using immunohistochemistry. Results Disease initiated with inflammation at the periphery of the intervertebral disc (IVD) adjacent to the longitudinal ligament, reminiscent of enthesitis, and was associated with upregulated tumor necrosis factor and metalloproteinases. After a lag phase, established inflammation was temporospatially associated with destruction of IVDs, cartilage and bone. At later time points, advanced disease was characterised by substantially reduced inflammation, excessive tissue formation and ectopic chondrocyte expansion. These distinct features differentiated affected mice into early, intermediate and advanced disease stages. Excessive tissue formation was observed in vertebral joints only if the IVD was destroyed as a consequence of the early inflammation. Ectopic excessive tissue was predominantly chondroidal with chondrocyte-like cells embedded within collagen type II- and X-rich matrix. This corresponded with upregulation of mRNA for cartilage markers Col2a1, sox9 and Comp. Osteophytes, though infrequent, were more prevalent in later disease. Conclusions The inflammation-driven IVD destruction was shown to be a prerequisite for axial disease progression to osteoproliferation in the PGISp mouse. Osteoproliferation led to vertebral body deformity and fusion but was never seen concurrent with persistent inflammation, suggesting a sequential process. The findings support that early intervention with anti-inflammatory therapies will be needed to limit destructive processes and consequently prevent progression of AS.

A multiple nucleotide length polymorphism (MNLP) mediates androgen regulation of IRX4 in prostate cancer

Androgens and the androgen receptor (AR) play a crucial role in the initiation and progression of prostate cancer (PCa), regulating the expression of many PCa risk-associated genes. Iroquois Homeobox 4 (IRX4) has been recently identified with PCa risk and overexpressed in PCa. We observed a down-regulation of IRX4 expression in the cells undergoing epithelial to mesenchymal transition, suggesting its potential role in PCa progression and aim to delineate the androgenmediated regulation of IRX4 in PCa.

Diverse bodies-space politics: Towards a critique of social (in)justice of built environment

Writing has long played an important role in the progression of architecture and the built environment. Histories of architecture are written, manifestoes that form the basis for a designer’s work are written and most importantly, the built environment advances itself through the act of critical writing. Not unlike the visual arts, literature and poetry, the tradition of written criticism has been crucial to the progression of architecture and its allied professions (Franz 2003). This article contributes to architecture and the built environment through the act of a written essay that critiques the problem of bodily diversity to architecture. In particular, the article explores the implications of body-space politics and abstracted body thinking on diverse bodies and their spatial justice. Using Soja’s Spatial Justice theory (2008), we seek to point out the underlying conceptions and power differentials assigned to different bodies spatially and how this leads to spatial injustices and contested spaces. The article also critically analyses the historical emergence of ‘the standardised body’ in architecture and its application in design theory and practice , and looks at how bodies often found on the outside of architecture highlight how such thinking creates in justices. Different theories are drawn on to help point to how design through the use of the upright, forward facing, male bod willingly and unwillingly denies access to resources and spatialities of everyday life. We also suggest ways to re-conceptualise the body in design practice and teaching.