Aims Ischaemic heart disease is the reduction of myocardial blood flow, caused by epicardial and/or microvascular disease. Both are common and prognostically important conditions, with distinct guideline-indicated management. Fractional flow reserve (FFR) is the current gold-standard assessment of epicardial coronary disease, but is only a surrogate of flow and only predicts percentage flow changes. It cannot assess absolute (volumetric) flow or microvascular disease. The aim of this study was to develop and validate a novel method that predicts absolute coronary blood flow and microvascular resistance (MVR) in the catheter laboratory. Methods and Results A computational fluid dynamics (CFD) model was used to predict absolute coronary flow (QCFD) and coronary microvascular resistance (MVR) using data from routine invasive angiography and pressure-wire assessment. QCFD was validated in an in vitro flow circuit which incorporated patient-specific, 3-D printed coronary arteries; and then in vivo, in patients with coronary disease. In vitro, QCFD agreed closely with the experimental flow over all flow rates (bias +2.08 mL/min; 95% CI (error range) -4.7 to + 8.8 mL/min; R2=0.999, p < 0.001; variability coefficient <1%). In vivo, QCFD and MVR were successfully computed in all 40 patients under baseline and hyperaemic conditions, from which coronary flow reserve (CFR) was also calculated. QCFD-derived CFR correlated closely with pressure-derived CFR (R2=0.92, P < 0.001). This novel method was significantly more accurate than Doppler-wire-derived flow both in vitro (±6.7 vs ± 34 mL/min) and in vivo (±0.9 vs ± 24.4 mmHg). Conclusions Absolute coronary flow and MVR can be determined alongside FFR, in absolute units, during routine catheter laboratory assessment, without the need for additional catheters, wires or drug infusions. Using this novel method, epicardial and microvascular disease can be discriminated and quantified. This comprehensive coronary physiological assessment may enable a new level of patient stratification and management. Translational Perspective Current pressure wire-based methods of assessing coronary disease cannot assess absolute flow or microvascular disease. Our novel QCFD method, using only angiography-based CFD and a pressure wire, simultaneously measures FFR, absolute coronary blood flow rate, microvascular resistance and coronary flow reserve. QCFD is suitable for use in the catheter laboratory and requires no dedicated catheters, wires or infusions. QCFD measures blood flow and microvascular resistance in absolute units and allows microvascular and epicardial disease to be differentiated, quantified and separately assessed, with the potential to improve diagnostic accuracy and clinical management.

It has been hypothesised that among different human subjects, the bone tissue quality varies as a function of the bone segment morphology. The aim of this study was to assess and compare the quality, evaluated in terms of hardness of packages of lamellae, of cortical and trabecular bones, at different anatomical sites within the human skeleton. The contralateral six long bones of an old human subject were indented at different levels along the diaphysis and at both epiphyses of each bone. Hardness value, which is correlated to the degree of mineralisation, of both cortical and trabecular bone tissues was calculated for each indentation location. It was found that the cortical bone tissue was harder (+18%) than the trabecular one. In general, the bone hardness was found to be locally highly heterogeneous. In fact, considering one single slice obtained for a bone segment, the coefficient of variation of the hardness values was up to 12% for cortical bone and up to 17% for trabecular bone. However, the tissue hardness was on average quite homogeneous within and among the long bones of the studied donor, although differences up to 9% among levels and up to 7% among bone segments were found. These findings seem not to support the mentioned hypothesis, at least not for the long bones of an old subject.

The hardness of cortical human bone has been measured on osteons in different conditions. However, no data are reported in the literature regarding the effect of cortical tissue condition and indentation location on the measured hardness values. This study aimed to investigate whether the hardness of the human cortical bone evaluated by micro-indentation is influenced, first, by the tissue condition and, second, by the distance of the indentation from the edge of the Haversian canal. Two femura were collected from a subject without musculoskeletal disease. The Vickers hardness was measured by means of microindentation (applied load, 100 gf) on osteons with a cross-section greater than 200 microm. The tests were performed on wet and embedded tissue at different distances from the Haversian canal edge (30-150 microm). No significant differences were found in hardness values between the two contralateral femura. Embedded tissue was significantly harder (12 per cent) than wet tissue. No significant differences were found in hardness values measured at different distances from the Haversian canal edge except for those closer than 60 microm. Therefore, indentations cannot be performed on osteons small in cross-section, since the distance from the closer pore has to be controlled. They should be performed on wet tissue, to avoid an offset in the measured hardness.