The EuroPhysiome, STEP and a roadmap for the virtual physiological human.

Biomedical science and its allied disciplines are entering a new era in which computational methods and technologies are poised to play a prevalent role in supporting collaborative investigation of the human body. Within Europe, this has its focus in the virtual physiological human (VPH), which is an evolving entity that has emerged from the EuroPhysiome initiative and the strategy for the EuroPhysiome (STEP) consortium. The VPH is intended to be a solution to common infrastructure needs for physiome projects across the globe, providing a unifying architecture that facilitates integration and prediction, ultimately creating a framework capable of describing Homo sapiens in silico. The routine reliance of the biomedical industry, biomedical research and clinical practice on information technology (IT) highlights the importance of a tailor-made and robust IT infrastructure, but numerous challenges need to be addressed if the VPH is to become a mature technological reality. Appropriate investment will reap considerable rewards, since it is anticipated that the VPH will influence all sectors of society, with implications predominantly for improved healthcare, improved competitiveness in industry and greater understanding of (patho)physiological processes. This paper considers issues pertinent to the development of the VPH, highlighted by the work of the STEP consortium.

Radiosurgery planning supported by the GEMSS grid.

GEMSS (Grid Enabled Medical Simulation Services IST-2001-37153) is an EU project funded to provide a test bed for Grid-enabled health applications. Its purpose is evaluation of Grid computing in the health sector. The health context imposes particular constraints on Grid infrastructure design, and it is this that has driven the feature set of the middleware. In addition to security, the time critical nature of health applications is accommodated by a Quality of Service component, and support for a well defined business model is also included. This paper documents experience of a GEMSS compliant radiosurgery application running within the Medical Physics department at the Royal Hallamshire Hospital in the UK. An outline of the Grid-enabled RAPT radiosurgery application is presented and preliminary experience of its use in the hospital environment is reported. The performance of the software is compared against GammaPlan (an industry standard) and advantages/disadvantages are highlighted. The RAPT software relies on features of the GEMSS middleware that are integral to the success of this application, and together they provide a glimpse of an enabling technology that can impact upon patient management in the 21st century.

A practical demonstration of improved technique factors in paediatric fluoroscopy.

Dose incurred with fluoroscopic procedures accounts for a significant proportion of medically induced diagnostic exposure. Children are particularly vulnerable and it is therefore important to minimize exposure where practicable. A recent theoretical study has highlighted the potential for X-ray equipment to produce significant dose savings during paediatric fluoroscopy without incurring loss of diagnostic image quality. This is achieved by hardening the beam with additional copper (Cu) filtration (approximately 0.2 mm Cu) and biasing exposure factors towards low tube potential, high tube current output. In practice, this method will have limited applicability because the high powered and programmable generator characteristics required are not commonly available in installations used for paediatric imaging. However, we describe a simple experiment in which our clinical equipment was modified to approximate desired low dose performance by altering the filtration and automatic exposure control characteristics of ordinary clinical equipment in the Sheffield Children's Hospital. This enabled us to obtain significant savings in dose. We performed a comparative study (normal dose vs low dose) using water phantoms to simulate patient attenuation in the age range 0-15 years. The Leeds N2 contrast sensitivity phantom was used to provide a measure of image quality. Dosimetric measurements recorded up to 40% reduction in dose rate with only marginal loss of image quality when 0.1-0.2 mm Cu filtration was used with the modified settings. This is a strong indication that significant dose reduction is achievable on routine clinical equipment without compromising image quality. Such simple and cost effective methods of dose reduction should be considered for wider implementation.

The effects of cardioplegic arrest and reperfusion on the microvasculature of the heart.

OBJECTIVES: Despite laboratory evidence of leucocyte involvement in reperfusion injury, cardiac surgical clinical trials do not support the therapeutic effectiveness of leucocyte filtration. Furthermore, the direct effects of crystalloid cardioplegia and reperfusion on the capillaries of the heart have yet to be elucidated. We tested the effects of cardioplegic arrest and reperfusion both with and without leucocyte depletion, in a model of cardiopulmonary bypass that mimics clinical cardiac surgical conditions. METHODS: Four groups of Landrace pigs were studied. Group A (n = 6) underwent 30 min of hypothermic (28 degrees C) cardiopulmonary bypass. Groups B (n = 6), C (n = 6) and D (n = 6) also had 90 min of cardioplegic arrest. Group C was then reperfused with whole blood, while Group D was reperfused with leucocyte-depleted blood. Microvascular methylmethacrylate corrosion casts were made at the end of the experimental period. Myocardial vascular anatomy was defined by electron microscopy and capillary abundance derived from this and from the weight of casts from representative areas. Leucocyte deposition was assessed using radioisotope-labelled leucocytes. Ischaemic damage to tissues was graded according to light and electron microscopic findings. RESULTS: In Group A the mean (+/- S.D.) vascular cast weight/volume of myocardium (density) was 125 +/- 9 mg/mm3. After cardioplegic arrest (Group B), it fell to 74 +/- 7 mg/mm3 (P < 0.0001) due to absence of capillaries, although arterioles, venules and non-nutritive bypass vessels remained patent. Following reperfusion with whole blood (Group C), capillary numbers partially recovered but luminal diameters were reduced with a cast density of 94 +/- 5 mg/mm3 (P < 0.0001 versus Group A and B). Leucocyte-depleted (87-92%) reperfusion in Group D did not affect cast density (90 +/- 3 mg/mm3; P = 0.17). Coronary vascular resistances in Groups C and D rose slightly, but not significantly, during reperfusion. CONCLUSIONS: Following cardioplegic arrest, microvascular changes are marked. These changes are partially reversed by 30 min reperfusion. Leucocyte depletion does not ameliorate these effects in this model.

Laser profiling: a technique for the study of prosthetic heart valve leaflet motion.

A detailed understanding of the stresses and strains developed in functioning flexible-leaflet valves is necessary if a durable, non-thrombogenic heart valve replacement is to be realized. A new experimental tool, laser profiling, is presented for the study of flexible-leaflet heart valve dynamics. Profiles of moving leaflet surfaces are obtained by projecting parallel sheets of laser light onto valve leaflets as the valves open and close in a mock circulatory loop. Two versions of laser profiling have been developed. In two-dimensional mode multiple profiles are generated on a fixed plane in space but at discrete intervals in time, whereas in three-dimensional mode multiple profiles are generated across the leaflet surface at (effectively) a single instant in time. Highlighted leaflet profiles are captured by camera and transferred to an image processing system for analysis. A simple algorithm permits digitized profiles to be reconstructed within a computer-aided design software package, providing detailed visualization and quantification of valve motion. Extensive validation studies have been performed using the Medtronic-Hall mechanical prosthetic heart valve. Laser profiling enables computer reconstruction of the rigid occluder to an accuracy of +/- 200 microns from a 0.7 ms exposure taken during the period at which the occluder moves with greatest velocity. The technique has been applied to investigate the leaflet dynamics of a bovine pericardial heart valve prosthesis.

Dehydration: a model for (low-temperature) argon laser tissue bonding.

Despite considerable investigation, the mechanism of laser assisted vascular anastomosis remains unknown. Indications suggest that bonding is the result of thermal action, particularly the thermal denaturation of tissue proteins. However, our own work has led us to conclude that dehydration is an important factor. Hence, we have proposed that laser anastomosis is the result of dehydration at the apposed tissue faces, induced by laser irradiation. This was investigated by comparing the properties of bonds created by dehydration with those created by laser. The bonds were created using parameters consistent with laser anastomoses created in vivo. Results revealed that anastomoses created by dehydration were equivalent to those created by laser, with little difference in strength, histology or response to rehydration. The only significant difference (p < 0.02) was mean bond strength created at temperatures above the denaturation temperature of the tissue (548 g cm(-2) by laser, 994 g cm(-2) by dehydration). Given the similarity of bonds created by the two methods, we conclude that the same mechanism (i.e. dehydration) is likely to be responsible for bonding in both cases and therefore that argon laser bonding is mediated by dehydration.