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Glucose concentration in type 1 diabetes is a function of biological and environmental factors which present high inter-patient variability. The objective of this study is to evaluate a number of features, which are extracted from medical and lifestyle self-monitoring data, with respect to their ability to predict the short-term subcutaneous (s.c.) glucose concentration of an individual. Random forests (RF) and RReliefF algorithms are first employed to rank the candidate feature set. Then, a forward selection procedure follows to build a glucose predictive model, where features are sequentially added to it in decreasing order of importance. Predictions are performed using support vector regression or Gaussian processes. The proposed method is validated on a dataset of 15 type diabetics in real-life conditions. The s.c. glucose profile along with time of the day and plasma insulin concentration are systematically highly ranked, while the effect of food intake and physical activity varies considerably among patients. Moreover, the average prediction error converges in less than d/2 iterations (d is the number of features). Our results suggest that RF and RReliefF can find the most informative features and can be successfully used to customize the input of glucose models. [ABSTRACT FROM AUTHOR]

The propagation of ultrasound in healing long bones induces complex scattering phenomena due to the interaction of an ultrasonic wave with the composite nature of callus and osseous tissues. This work presents numerical simulations of ultrasonic propagation in healing long bones using the boundary element method aiming to provide insight into the complex scattering mechanisms and better comprehend the state of bone regeneration. Numerical models of healing long bones are established based on scanning acoustic microscopy images from successive postoperative weeks considering the effect of the nonhomogeneous callus structure. More specifically, the scattering amplitude and the acoustic pressure variation are calculated in the backward direction to investigate their potential to serve as quantitative and qualitative indicators for the monitoring of the bone healing process. The role of the excitation frequency is also examined considering frequencies in the range 0.2-1 MHz. The results indicate that the scattering amplitude decreases at later stages of healing compared to earlier stages of healing. Also, the acoustic pressure could provide supplementary qualitative information on the interaction of the scattered energy with bone and callus. [ABSTRACT FROM AUTHOR]

Background: The prevention of hypoglycemic events is of paramount importance in the daily management of insulin-treated diabetes. The use of short-term prediction algorithms of the subcutaneous (s.c.) glucose concentration may contribute significantly toward this direction. The literature suggests that, although the recent glucose profile is a prominent predictor of hypoglycemia, the overall patient's context greatly impacts its accurate estimation. The objective of this study is to evaluate the performance of a support vector for regression (SVR) s.c. glucose method on hypoglycemia prediction. Materials and Methods: We extend our SVR model to predict separately the nocturnal events during sleep and the nonnocturnal (i.e., diurnal) ones over 30-min and 60-min horizons using information on recent glucose profile, meals, insulin intake, and physical activities for a hypoglycemic threshold of 70 mg/dL. We also introduce herein additional variables accounting for recurrent nocturnal hypoglycemia due to antecedent hypoglycemia, exercise, and sleep. SVR predictions are compared with those from two other machine learning techniques. Results: The method is assessed on a dataset of 15 patients with type 1 diabetes under free-living conditions. Nocturnal hypoglycemic events are predicted with 94% sensitivity for both horizons and with time lags of 5.43 min and 4.57 min, respectively. As concerns the diurnal events, when physical activities are not considered, the sensitivity is 92% and 96% for a 30-min and 60-min horizon, respectively, with both time lags being less than 5 min. However, when such information is introduced, the diurnal sensitivity decreases by 8% and 3%, respectively. Both nocturnal and diurnal predictions show a high ( > 90%) precision. Conclusions: Results suggest that hypoglycemia prediction using SVR can be accurate and performs better in most diurnal and nocturnal cases compared with other techniques. It is advised that the problem of hypoglycemia prediction should be handled differently for nocturnal and diurnal periods as regards input variables and interpretation of results. [ABSTRACT FROM AUTHOR]

The classical linear theory of elasticity has been largely used for the ultrasonic characterization of bone. However, linear elasticity cannot adequately describe the mechanical behavior of materials with microstructure in which the stress state has to be defined in a non-local manner. In this study, the simplest form of gradient theory (Mindlin Form-II) is used to theoretically determine the velocity dispersion curves of guided modes propagating in isotropic bone-mimicking plates. Two additional terms are included in the constitutive equations representing the characteristic length in bone: (a) the gradient coefficient g, introduced in the strain energy, and (b) the micro-inertia term h, in the kinetic energy. The plate was assumed free of stresses and of double stresses. Two cases were studied for the characteristic length: h=10-4 m and h=10-5 m. For each case, three subcases for g were assumed, namely, g>h, g

Abstract: Guided wave propagation has recently drawn significant interest in the ultrasonic characterization of bone. In this work, we present a two-dimensional computational study of ultrasound propagation in healing bones aiming at monitoring the fracture healing process. In particular, we address the effect of fluid loading boundary conditions on the characteristics of guided wave propagation, using both time and time–frequency (t−f) signal analysis techniques, for three study cases. In the first case, the bone was assumed immersed in blood which occupied the semi-infinite spaces of the upper and lower surfaces of the plate. In the second case, the bone model was assumed to have the upper surface loaded by a 2mm thick layer of blood and the lower surface loaded by a semi-infinite fluid with properties close to those of bone marrow. The third case, involves a three-layer model in which the upper surface of the plate was again loaded by a layer of blood, whereas the lower surface was loaded by a 2mm layer of a fluid which simulated bone marrow. The callus tissue was modeled as an inhomogeneous material and fracture healing was simulated as a three-stage process. The results clearly indicate that the application of realistic boundary conditions has a significant effect on the dispersion of guided waves when compared to simplified models in which the bone’s surfaces are assumed free. [Copyright &y& Elsevier]

Quantitative ultrasound has attracted significant interest in the evaluation of bone fracture healing. Animal and clinical studies have demonstrated that the propagation velocity across fractured bones can be used as an indicator of healing. Researchers have recently employed computational methods for modeling wave propagation in bones, aiming to gain insight into the underlying mechanisms of wave propagation and to further enhance the monitoring capabilities of ultrasound. In this paper, we review the relevant literature and present the current status of knowledge. [ABSTRACT FROM AUTHOR]

The use of guided waves has recently drawn significant interest in the ultrasonic characterization of bone aiming at supplementing the information provided by traditional velocity measurements. This work presents a three-dimensional finite element study of guided wave propagation in intact and healing bones. A model of the fracture callus was constructed and the healing course was simulated as a three-stage process. The dispersion of guided modes generated by a broadband 1-MHz excitation was represented in the time-frequency domain. Wave propagation in the intact bone model was first investigated and comparisons were then made with a simplified geometry using analytical dispersion curves of the tube modes. Then, the effect of callus consolidation on the propagation characteristics was examined. It was shown that the dispersion of guided waves was significantly influenced by the irregularity and anisotropy of the bone. Also, guided waves were sensitive to material and geometrical changes that take place during healing. Conversely, when the first-arriving signal at the receiver corresponded to a nondispersive lateral wave, its propagation velocity was almost unaffected by the elastic symmetry and geometry of the bone and also could not characterize the callus tissue throughout its thickness. In conclusion, guided waves can enhance the capabilities of ultrasonic evaluation. [ABSTRACT FROM AUTHOR]

Abstract: Ultrasonic evaluation of bone fracture healing has been traditionally based on the measurement of the propagation velocity of the first arriving signal (FAS). However, the FAS in general corresponds to a lateral wave that propagates along the bone’s subsurface. In this work, we study guided ultrasound propagation in intact and healing bones. We developed a 2-D model of a bone-mimicking plate in which the healing process was simulated as a 7-stage process, and we also carried out ex vivo experiments on an intact tibia. Guided waves were represented in the time-frequency (t-f) domain of the signal by incorporating the Lamb wave theory. Three t-f distribution functions were examined, namely the reassigned Spectrogram, the smoothed-pseudo Wigner-Ville, and the reassigned version of it. For the intact plate case, we found that the S2, A3 Lamb modes were the dominant waves for a broadband 1-MHz excitation, and the S2, S0 for a 500-kHz excitation. During the simulated healing process, the mechanical and geometrical callus properties affected the theoretically anticipated Lamb modes. The propagation of guided waves throughout the thickness of the cortical bone and their sensitivity to both the mechanical and structural changes during healing can supplement velocity measurements so as to enhance the monitoring capabilities of ultrasonic evaluation. Nevertheless, the applicability of the Lamb wave theory to real bones has several limitations mostly associated with neglecting the inhomogeneity, anisotropy and irregular geometry of bone. (E-mail: fotiadis@cs.uoi.gr) [Copyright &y& Elsevier]

An ultrasound wearable system for remote monitoring and acceleration of the healing process in fractured long bones is presented. The so-called USBone system consists of a pair of ultrasound transducers, implanted into the fracture region, a wearable device and a centralized unit. The wearable device is responsible to carry out ultrasound measurements using the axial-transmission technique and initiate therapy sessions of low-intensity pulsed ultrasound. The acquired measurements and other data are wirelessly transferred from the patient-site to the centralized unit, which is located in a clinical setting. The evaluation of the system on an animal tibial osteotomy model is also presented. A dataset was constructed for monitoring purposes consisting of serial ultrasound measurements, follow-up radiographs, quantitative computed tomography-based densitometry and biomechanical data. The animal study demonstrated the ability of the system to collect ultrasound measurements in an effective and reliable fashion and participating orthopaedic surgeons accepted the system for future clinical application. Analysis of the acquired measurements showed that the pattern of evolution of the ultrasound velocity through healing bones over the postoperative period monitors a dynamic healing process. Furthermore, the ultrasound velocity of radiographically healed bones returns to 80% of the intact bone value, whereas the correlation coefficient of the velocity with the material and mechanical properties of the healing bone ranges from 0.699 to 0.814. The USBone system constitutes the first telemedicine system for the out-hospital management of patients sustained open fractures and treated with external fixation devices. [ABSTRACT FROM AUTHOR]

Highlights: [•] The theoretical results were in consistency with experimental findings. [•] Wave dispersion varied according to the examined healing stage. [•] The attenuation coefficient varied according to the examined healing stage. [•] The dominant dispersion modes were gradually restored at the final healing stages. [ABSTRACT FROM AUTHOR]

Cortical bone is a multiscale heterogeneous natural material characterized by microstructural effects. Thus guided waves propagating in cortical bone undergo dispersion due to both material microstructure and bone geometry. However, above 0.8 MHz, ultrasound propagates rather as a dispersive surface Rayleigh wave than a dispersive guided wave because at those frequencies, the corresponding wavelengths are smaller than the thickness of cortical bone. Classical elasticity, although it has been largely used for wave propagation modeling in bones, is not able to support dispersion in bulk and Rayleigh waves. This is possible with the use of Mindlin's Form-II gradient elastic theory, which introduces in its equation of motion intrinsic parameters that correlate microstructure with the macrostructure. In this work, the boundary element method in conjunction with the reassigned smoothed pseudo Wigner-Ville transform are employed for the numerical determination of time-frequency diagrams corresponding to the dispersion curves of Rayleigh and guided waves propagating in a cortical bone. A composite material model for the determination of the internal length scale parameters imposed by Mindlin's elastic theory is exploited. The obtained results demonstrate the dispersive nature of Rayleigh wave propagating along the complex structure of bone as well as how microstructure affects guided waves. [ABSTRACT FROM AUTHOR]

Abstract: The purpose of this study is twofold: (a) to investigate the application of transosseous low-intensity pulsed ultrasound (LiUS) on the enhancement of fracture healing and (b) to demonstrate the ability of transosseous ultrasound propagation to monitor the healing process. A midshaft tibial osteotomy model was used on 40 skeletally mature sheep, and an external fixator was applied to maintain the reduction and stabilization of the osteotomy. Two ultrasound transducers were implanted into the fracture site in contact with the bone. For investigating the efficacy of LiUS, the animals were randomly divided in two equal groups: the treatment group and the control group. The LiUS-treated animals received 200-μs bursts of 1-MHz sine waves with a pulse repetition rate of 1 kHz and average intensity of 30 mW/cm2, for 20 min daily. For monitoring purposes, an ultrasound dataset was constructed consisting of serial ultrasound measurements obtained from healing bones. Animals'' sacrifice took place on the 100th post-operative day. The effect of LiUS on fracture healing was evaluated using radiographs, destructive three-point bending testing and quantitative CT-based bone mineral density (BMD) measurements. Survival analysis using Kaplan–Meier curves showed significantly higher probability of radiographic healing for the animals in the treatment group (P = 0.009). Statistical significance was also observed for callus BMD (P = 0.003, Wilcoxon nonparametric test), the breaking load (P = 0.001), extrinsic stiffness (P = 0.019), Young''s modulus (P = 0.043) and ultimate strength (P = 0.051) in favor of the LiUS-treated limbs. Analysis of the obtained ultrasonic measurements showed that the propagation velocity across healing bones constitutes a significant feature able to early distinguish between healed and nonhealed bones (area under ROC curve was 0.810 and 0.841 on the 80th and 100th post-operative days, respectively). Both the LiUS application and the ultrasonic measurements are supported by an integrated telemedicine system which also incorporates an ultrasound wearable device and a patient management system. [Copyright &y& Elsevier]

Computational studies on the evaluation of bone status in cases of pathologies have gained significant interest in recent years. This work presents a parametric and systematic numerical study on ultrasound propagation in cortical bone models to investigate the effect of changes in cortical porosity and the occurrence of large basic multicellular units, simply called non-refilled resorption lacunae (RL), on the velocity of the first arriving signal (FAS). Two-dimensional geometries of cortical bone are established for various microstructural models mimicking normal and pathological tissue states. Emphasis is given on the detection of RL formation which may provoke the thinning of the cortical cortex and the increase of porosity at a later stage of the disease. The central excitation frequencies 0.5 and 1 MHz are examined. The proposed configuration consists of one point source and multiple successive receivers in order to calculate the FAS velocity in small propagation paths (local velocity) and derive a variation profile along the cortical surface. It was shown that: (a) the local FAS velocity can capture porosity changes including the occurrence of RL with different number, size and depth of formation; and (b) the excitation frequency 0.5 MHz is more sensitive for the assessment of cortical microstructure. [ABSTRACT FROM AUTHOR]

Abstract: The present study investigates the effect of transosseous low-intensity pulsed ultrasound (LiUS) on the healing at tendon graft-bone interface, in molecular and histological level. The anterior cruciate ligament (ACL) in both knees of 52 New Zealand White rabbits was excised and replaced with the long digital extensor. A custom-made ultrasound transducer was implanted onto the medial tibial condyle, adjacent to the surface of the bone tunnel at both knees of the rabbits. The LiUS-treated right knees received 200-μs bursts of 1 MHz sine waves at a pulse repetition rate of 1 kHz and with 30 mW/cm2 spatial-average temporal-average intensity for 20 min daily (study group), while the left knee received no LiUS (control group). Thirty-six rabbits were used to perform semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) analysis from both study and control groups for transforming growth factor-β1 (TGF-β1), biglycan and collagen I. RT-PCR products showed statistically significant upregulation of biglycan and collagen I gene expression in the study group, while TGF-β1 gene expression exhibited a bimodal profile. Histological examination performed in 16 rabbits from both groups supported the findings of the molecular analysis, indicating a faster healing rate and a more efficient ligamentization process after ultrasound treatment. These findings suggest that transosseous application of LiUS enhances the healing rate of the tendon graft-bone interface, possibly by affecting the expression levels of genes significant for the tendon to bone healing process. (E-mail: malizos@med.uth.gr) [Copyright &y& Elsevier]