Optimisation of the digital radiographic imaging of suspected non-accidental injury.

Aim: To optimise the digital (radiographic) imaging of children presenting with suspected non-accidental injury (NAI).;Objectives: (i) To evaluate existing radiographic quality criteria, and to develop a more suitable system if these are found to be inapplicable to skeletal surveys obtained in suspected NAI. (ii) To document differences in image quality between conventional film-screen and the recently installed Fuji5000R computed radiography (CR) system at Great Ormond Street Hospital for Children, (iii) To document the extent of variability in the standard of skeletal surveys obtained in the UK for suspected NAI. (iv) To determine those radiographic parameters which yield the highest diagnostic accuracy, while still maintaining acceptable radiation dose to the child, (v) To determine how varying degrees of edge-enhancement affect diagnostic accuracy. (vi) To establish the accuracy of soft compared to hard copy interpretation of images in suspected NAI.;Materials and Methods: (i) and (ii) Retrospective analysis of 286 paediatric lateral spine radiographs by two observers based on the Commission of European Communities (CEC) quality criteria, (iii) Review of the skeletal surveys of 50 consecutive infants referred from hospitals throughout the United Kingdom (UK) with suspected NAI. (iv) Phantom studies. Leeds TO. 10 and TO. 16 test objects were used to compare the relationship between film density, exposure parameters and visualisation of object details, (iv) Clinical study. Anteroposterior and lateral post mortem skull radiographs of six consecutive infants were obtained at various exposures. Six observers independently scored the images based on visualisation of five criteria, (v) and (vi) A study of diagnostic accuracy in which six observers independently interpreted 50 radiographs from printed copies (with varying degrees of edge-enhancement) and from a monitor.;Results: The CEC criteria are useful for optimisation of imaging parameters and allow the detection of differences in quality of film-screen and digital images. There is much variability in the quality and number of radiographs performed as part of skeletal surveys in the UK for suspected NAI. The Leeds test objects are either not sensitive enough (TO. 10) or perhaps over sensitive (TO. 16) for the purposes of this project. Furthermore, the minimum spatial resolution required for digital imaging in NAI has not been established. Therefore the objective interpretation of phantom studies is difficult. There is scope for reduction of radiation dose to children with no effect on image quality. Diagnostic accuracy (fracture detection) in suspected NAI is generally low, and is not affected by image display modality.;Conclusions: The CEC quality criteria are not applicable to the assessment of clinical image quality. A national protocol for skeletal surveys in NAI is required. Dedicated training, close supervision, collaboration and consistent exposure of radiologists to cases of NAI should improve diagnostic accuracy. The potential exists for dose reduction when performing skeletal surveys in children and infants with suspected NAI. Future studies should address this issue

Evaluation of Vibration Analysis to Assess Bone Mineral Density in Children

The effectiveness of vibration analysis to assess bone mineral density (BMD) in children with suspected reduction in bone density was studied. A system was designed that measured the ulna's vibration responses in vivo. The system was evaluated on the ulnae of 48 children (mean age=12.0, std=3.5 years), 31 of whom had been confirmed to have osteogenesis imperfecta (OI). All children had dual energy X-ray absorptiometry (DXA) scan as part of their routine clinical care and vibration analysis was performed on the same day. Frequency spectra of the ulnae's vibration responses were obtained and processed by principal component analysis. Four main principal components were selected and together with age, sex and right hand ulna's length were used in a regression analysis to estimate BMD. Regression analysis was repeated using the children's leave-one-out and partitioning methods. The percentage similarity and correlation between the DXA-derived and vibration analysis estimated BMDs using the leave-one-out were 80.34% and 0.59 and for partitioning were 74.2% and 0.64 respectively. There was correlation between vibration analysis BMD readings and those derived from DXA however a larger study will be needed to better establish the extent to which vibration analysis can assist in assessing bone density in clinical environments

The radiologic diagnosis of skeletal dysplasias : past, present and future

Skeletal dysplasias have been recognised since recorded history began. The advent of radiography at the beginning of the 20th century and the subsequent introduction of departments of radiology have had tremendous impact and allowed conditions to be identified by their specific radiographic phenotypes. This has been enhanced by the addition of cross-sectional modalities (ultrasound, computed tomography and magnetic resonance imaging), which have allowed for prenatal recognition and diagnosis of skeletal dysplasias, and by the recent explosion in identified genes. There are more than 400 recognised skeletal dysplasias, many of which (due to their rarity) the practising clinician (radiologist, paediatrician, geneticist) may never come across. This article provides a historical overview of aids to the radiologic diagnosis of skeletal dysplasias

Assessing material densities by vibration analysis and independent component analysis

The aim of this study was to investigate vibration analysis and independent component analysis (ICA) to assess the density of multiple materials making up a single structure. Density is important as it reveals information about physical properties of materials. The density of a single material can be determined from the relationship between its mass and volume. However, when a structure consists of multiple materials, identification of their individual densities from the structure is complicated. Vibration analysis is a technique that reveals information about an object’s physical properties such as its density. The investigation was carried out using a plastic test tube filled separately with three liquids of known densities; water, Chloroform and Methanol. Vibration was inducted into the tube, through an electronic system that produced a single impact at a predefined location on the tube. The resulting vibration signals were recorded using two vibration sensors placed on the tube. A signal source separation technique called ICA was used to obtain the vibration effects of the liquid and the tube. The power spectral densities (PSD) of ICA extracted vibration signals were examined. The frequency of the largest peak in the PSD was related to the liquid’s density under test. The study indicated that vibration analysis may be effective in assessing materials’ densities in a structure that contains multiple materials, however a larger study is needed to explore the findings

High-Risk Breast Lesions

It is well known that certain types of pre-malignant lesions can predispose some women to increased risk of breast cancer. These certain types of pre-malignant lesions are generally classified as high-risk breast lesions. These lesions become invasive cancers in about 15% of patients and hence the management and treatment of these lesions warrant a significant discussion. There are several categories of these lesions, to include atypical hyperplasia of the breast (atypical ductal hyperplasia and atypical lobular hyperplasia); carcinoma in situ (ductal carcinoma in situ and lobular carcinoma in situ); columnar cell pre-malignant lesions; lobular intraepithelial neoplasia (LIN III); radial scar/complex sclerosing lesion; sclerosing adenosis and papillary lesions of the breast. These lesions are morphologically, radiologically, histologically and clinically heterogeneous and early identification can help to prevent progression to invasive cancers. The management of these lesions has been debated internationally for years by experts as to the best treatment modality with surgical excision of the lesion often not considered necessary. It is thus important to evaluate each patient on an individual case-by-case basis. The characteristics of these high-risk breast lesions are further discussed in this chapter

Elevated platelet counts in a cohort of children with moderate-severe osteogenesis imperfecta suggest that inflammation is present

BACKGROUND: Elevated platelet counts are observed in cancer, autoimmunity and inflammation with concurrent illness. Proinflammatory cytokines are elevated in murine osteogenesis imperfecta (OI) models. We hypothesised that platelet counts might be elevated in children with moderate-severe OI. METHODS: We reviewed the hospital records of 71 children with moderate-severe OI, treated in the Sheffield Children's Hospital's Severe, Complex and Atypical Osteogenesis Imperfecta Highly Specialised Service. Data relating platelet count (below/above average, above upper limit) to prior and concurrent events were summarised as event proportions per child. Additionally, we created platelet SD scores to assess age and time-related trends, and relationship with OI type. RESULTS: 1206 platelet counts were recorded. Platelet SD scores were right-shifted by 0.89 SD overall. 49 of 71 (69%) patients had at least one platelet count above the normal range and 246 (20.4%) of all counts were above the upper limit of normal. Of these, 101 (41%) were high despite no confounding factors being present. For the 47 children with data at age less than 2 years, 89 (30.0%) platelet counts were above the upper limit of normal and 39 (44%) had no associated confounding factor. Elevated platelet counts were recorded most often for children with new or existing vertebral fractures. CONCLUSIONS: Raised platelet counts were observed in association with new and healing vertebral fractures, but also (41%-44%) in the absence of identified proinflammatory factors or events. We speculate that these findings are evidence for a proinflammatory component to OI that could be a target for therapeutic intervention

Feasibility of quantitative ultrasonography for the detection of metabolic bone disease in preterm infants - systematic review.

Metabolic bone disease of prematurity is characterised by disordered bone mineralisation and is therefore an increased fracture risk. Preterm infants are especially at risk due to incomplete in utero bone accretion during the last trimester. Currently, diagnosing metabolic bone disease mainly relies on biochemistry and radiographs. Dual-energy x-ray absorptiometry and quantitative ultrasound (US) are used less frequently. However, biochemical measurements correlate poorly with bone mineralisation and although scoring systems exist for metabolic bone disease, radiographs are subjective and do not detect early features of osteopenia. Dual energy x-ray absorptiometry is the reference standard for determining bone density in older children and adults. However, challenges with this method include movement artefact, difficulty scanning small and sick infants and a lack of normative data for young children. Quantitative US has a relatively low cost, is radiation-free and portable, and may hence be suitable for assessing bone status in preterm infants. This review aims to provide an overview of the use of quantitative US in detecting metabolic bone disease in preterm infants

Imaging and reporting considerations for suspected physical abuse (non-accidental injury) in infants and young children. Part 2: axial skeleton and differential diagnoses

Recognising the skeletal manifestations of inflicted injury (II) in infants and young children is of crucial importance. There are specific fracture patterns which are highly suspicious of II in addition to common differential diagnoses with which radiologists should be familiar. Our objective is to provide a non-exhaustive review of the important factors relevant to the imaging and reporting of II as a platform for further learning. Part 2 encompasses fracture patterns of the axial skeleton and important differential diagnoses

Junctional Adhesion Molecules (JAMs) - New Players in Breast Cancer?

Worldwide, breast cancer remains a leading cause of death amongst women. Annually, it i sestimated that breast cancer is diagnosed in over a million women (Kasler et al., 2009) with over 450,000 deaths worldwide (Tirona et al., 2010). The incidence of the disease is highest in economically-developed countries, with lower rates in developing countries. Despite continual advances in breast cancer care which have led to reduced mortality, however, the incidence of the disease is still rising. The decrease in breast cancer-specific mortality has been attributed to improvements in screening techniques which permit earlier detection, surgical and radiotherapy interventions, better understanding of disease pathogenesis and utilization of traditional chemotherapies in a more efficacious manner. Consequently, early stage breast cancer is now a curable disease while advanced breast cancer remains asignificant clinical problem. Breast cancer is a heterogeneous disease encompassing many subtypes, which differ both in terms of their molecular backgrounds and clinical prognosis. These breast cancer subtypes range from pre-invasive early stage disease to advanced invasive disease. The simplest classifications of disease subdivide breast cancer into pre-invasive and invasive forms; with the pre-invasive forms being ductal carcinoma in situ (DCIS) and lobular carcinoma in situ (LCIS). Carcinoma in situ is proliferation of cancer cells within the epithelial tissue without invasion of the surrounding stromal tissue (Bland & Copeland, 1998). DCIS arises in the terminal ductal lobular units (TDLU) and in extra-lobular ducts while LCIS occurs in the breast lobules, and is recognisable histopathologically by the presence of populations of aberrant cells with small nuclei (Hanby & Hughes, 2008). Invasive breast cancers are subclassified into invasive ductal breast cancer, invasive lobular breast cancer, inflammatory breast cancer and Paget's disease. Invasive ductal carcinoma (IDC) is the most common formof invasive breast cancer, accounting for around 85% of all cases. DCIS is frequently considered as an obligate precursor to IDC, progressing from lower to higher grades and then onto invasive cancer with progressive accumulation of genomic changes (Farabegoli et al ., 2002). However it has alternately been suggested that there exist genetically-distinct subgroups of DCIS, only some of which have the potential to progress to invasion (Shackney & Silverman, 2003). Long-term natural history studies of DCIS have provided supportive evidence for both possibilities (Page et al., 1995; Collins et al ., 2005; Sanders et al ., 2005). Despite such controversies, the large extent to which the genome is altered in DCIS strongly suggests that genomic instability precedes phenotypic evidence of invasion (Hwang et al ., 2004). This serves to underline the fact that malignant transformation in a heterogeneous disease like breast cancer is a dynamic process evolving through multiple multi-step pathway models. Many factors are thought to be responsible for the development of breast cancer. Genetic factors play a vital role in the predisposition to breast cancer, with mutations of BRCA1 and BRCA2 genes accounting for 5–10% of breast cancer cases and being responsible for 80% of inherited breast cancers (Nathanson et al., 2001). On a more complex level, much insight has been gained from the genetic profiling of thousands of tumours to generate gene signatures of prognostic value (Sorlie et al., 2001; van 't Veer et al., 2002; van de Vijver et al ., 2002), which have spurred the development of commercially-available diagnostic tests. The importance of reproductive factors in the aetiology of breast cancer is also well recognised with early onset of menarche, nulliparity, late menopause, endogenous and exogenous hormones representing the main risk factors (Reeves et al ., 2000; Key et al., 2001; Howell & Evans, 2011). Several other studies have reported anincreased risk of breast cancer with lack of physical activity (especially in pre menopausal women), as well as increasing age and obesity (Clarke et al ., 2006; Walker & Martin, 2007; Harrison et al., 2009; Rod et al., 2009; Awatef et al ., 2011). These risk factors accentuate the abnormal growth control of cells by increasing the circulating levels of oestrogen thereby promoting tumourigenesis within the breast microenvironment. A proper understandingof the breast cancer microenvironment is essential for understanding breast cancer, and will be explored in detail in the next sections. </p