High resolution cortical bone thickness measurement from clinical CT data.

The distribution of cortical bone in the proximal femur is believed to be a critical component in determining fracture resistance. Current CT technology is limited in its ability to measure cortical thickness, especially in the sub-millimetre range which lies within the point spread function of today's clinical scanners. In this paper, we present a novel technique that is capable of producing unbiased thickness estimates down to 0.3mm. The technique relies on a mathematical model of the anatomy and the imaging system, which is fitted to the data at a large number of sites around the proximal femur, producing around 17,000 independent thickness estimates per specimen. In a series of experiments on 16 cadaveric femurs, estimation errors were measured as -0.01+/-0.58mm (mean+/-1std.dev.) for cortical thicknesses in the range 0.3-4mm. This compares with 0.25+/-0.69mm for simple thresholding and 0.90+/-0.92mm for a variant of the 50% relative threshold method. In the clinically relevant sub-millimetre range, thresholding increasingly fails to detect the cortex at all, whereas the new technique continues to perform well. The many cortical thickness estimates can be displayed as a colour map painted onto the femoral surface. Computation of the surfaces and colour maps is largely automatic, requiring around 15min on a modest laptop computer.

Transposon mutagenesis in a hyper-invasive clinical isolate of Campylobacter jejuni reveals a number of genes with potential roles in invasion.

Transposon mutagenesis has been applied to a hyper-invasive clinical isolate of Campylobacter jejuni, 01/51. A random transposon mutant library was screened in an in vitro assay of invasion and 26 mutants with a significant reduction in invasion were identified. Given that the invasion potential of C. jejuni is relatively poor compared to other enteric pathogens, the use of a hyper-invasive strain was advantageous as it greatly facilitated the identification of mutants with reduced invasion. The location of the transposon insertion in 23 of these mutants has been determined; all but three of the insertions are in genes also present in the genome-sequenced strain NCTC 11168. Eight of the mutants contain transposon insertions in one region of the genome (approximately 14 kb), which when compared with the genome of NCTC 11168 overlaps with one of the previously reported plasticity regions and is likely to be involved in genomic variation between strains. Further characterization of one of the mutants within this region has identified a gene that might be involved in adhesion to host cells.

Mechanobiology of bone remodelling

Bone as most of living tissues is able, during its entire lifetime, to adapt its internal microstructure and subsequently its associated mechanical properties to the specific mechanical and physiological environment in a process commonly known as bone remodelling. Bone is therefore continuously renewed and microdamage removed minimizing the risk of fracture. Bone remodelling is controlled by mechanical and metabolical stimuli. In this paper, we introduce a new model of bone remodelling that takes into account both types of influences. The predicted results show a good correspondence with experimental and clinical data. For example, in disuse, bone porosity increases until an equilibrium situation, while, in overloading, decreases unless the damage rate is so high that causes resorption and "stress fracture". This model has been employed to predict bone adaptation in the proximal femur after total hip replacement proving its consistence and good correspondence with well-known clinical experiences.

Imaging the femoral cortex: thickness, density and mass from clinical CT.

There is growing evidence that focal thinning of cortical bone in the proximal femur may predispose a hip to fracture. Detecting such defects in clinical CT is challenging, since cortices may be significantly thinner than the imaging system's point spread function. We recently proposed a model-fitting technique to measure sub-millimetre cortices, an ill-posed problem which was regularized by assuming a specific, fixed value for the cortical density. In this paper, we develop the work further by proposing and evaluating a more rigorous method for estimating the constant cortical density, and extend the paradigm to encompass the mapping of cortical mass (mineral mg/cm(2)) in addition to thickness. Density, thickness and mass estimates are evaluated on sixteen cadaveric femurs, with high resolution measurements from a micro-CT scanner providing the gold standard. The results demonstrate robust, accurate measurement of peak cortical density and cortical mass. Cortical thickness errors are confined to regions of thin cortex and are bounded by the extent to which the local density deviates from the peak, averaging 20% for 0.5mm cortex.