Human skeletal muscle energy metabolism: when a physiological model promotes the search for new technologies

The idea that muscle function and, in fact, the function of all living tissues may be described by physical laws appeared in the second half of the 19th century. During this period, Helmoltz (Über die Erhaltung der Kraft, 1847) showed that the principle of energy conservation may be applied to living systems. In the field of exercise physiology, this idea has been subsequently developed by Rodolfo Margaria's (1901-1983) School and the mathematical formalization of the theory has succeeded in the bioenergetic model. During the last 20years methodical and critical study of the bioenergetic model has been carried out by Paolo Cerretelli, one of the most important heirs of Rodolfo Margaria's School. Original results and technological developments have been generated by his activity and many young scientists have been educated in this approach. The present paper wants to present the modern history of the bioenergetic model and is dedicated to Paolo Cerretelli on the occasion of his seventieth birthda

Probability density function for random photon steps in a binary (isotropic-Poisson) statistical mixture

Monte Carlo (MC) simulations allowing to describe photons propagation in statistical mixtures represent an interest that goes way beyond the domain of optics, and can cover, e.g., nuclear reactor physics, image analysis or life science just to name a few. MC simulations are considered a ``gold standard'' because they give exact solutions (in the statistical sense), however, in the case of statistical mixtures they are enormously time consuming and their implementation is often extremely complex. For this reason, the aim of the present contribution is to propose a new approach that should allow us in the future to simplify the MC approach. This is done through an explanatory example, i.e.; by deriving the `exact' analytical expression for the probability density function of photons' random steps (single step function, SSF) propagating in a medium represented as a binary (isotropic-Poisson) statistical mixture. The use of the SSF reduces the problem to an `equivalent' homogeneous medium behaving exactly as the original binary statistical mixture. This will reduce hundreds time-consuming MC simulations to only one equivalent simple MC simulation. To the best of our knowledge the analytically `exact' SSF for a binary (isotropic-Poisson) statistical mixture has never been derived before

Topological complexity of photons' paths in biological tissues

In the present contribution three means of measuring the geometrical and topological complexity of photons' paths in random media are proposed. This is realized by investigating the behavior of the average crossing number, the mean writhe, and the minimal crossing number of photons' paths generated by Monte Carlo (MC) simulations, for different sets of optical parameters. It is observed that the complexity of the photons' paths increases for increasing light source/detector spacing, and that highly "knotted" paths are formed. Due to the particular rules utilized to generate the MC photons' paths, the present results may have an interest not only for the biomedical optics community, but also from a pure mathematical point of view

There's plenty of light at the bottom: Statistics of photon penetration depth in random media

We propose a comprehensive statistical approach describing the penetration depth of light in random media. The presented theory exploits the concept of probability density function f(z|ρ, t) for the maximum depth reached by the photons that are eventually re-emitted from the surface of the medium at distance ρ and time t. Analytical formulas for f, for the mean maximum depth 〈zmax〉 and for the mean average depth 〈z〉 reached by the detected photons at the surface of a diffusive slab are derived within the framework of the diffusion approximation to the radiative transfer equation, both in the time domain and the continuous wave domain. Validation of the theory by means of comparisons with Monte Carlo simulations is also presented. The results are of interest for many research fields such as biomedical optics, advanced microscopy and disordered photonics

Time-domain Raman analytical forward solvers

A set of time-domain analytical forward solvers for Raman signals detected from homogeneous diffusive media is presented. The time-domain solvers have been developed for two geometries: the parallelepiped and the finite cylinder. The potential presence of a background fluorescence emission, contaminating the Raman signal, has also been taken into account. All the solvers have been obtained as solutions of the time dependent diffusion equation. The validation of the solvers has been performed by means of comparisons with the results of "gold standard" Monte Carlo simulations. These forward solvers provide an accurate tool to explore the information content encoded in the time-resolved Raman measurements

Two-step verification method for Monte Carlo codes in biomedical optics applications

Significance: Code verification is an unavoidable step prior to using a Monte Carlo (MC) code. Indeed, in biomedical optics, a widespread verification procedure for MC codes is still missing. Analytical benchmarks that can be easily used for the verification of different MC routines offer an important resource.Aim: We aim to provide a two-step verification procedure for MC codes enabling the two main tasks of an MC simulator: (1) the generation of photons' trajectories and (2) the intersections of trajectories with boundaries separating the regions with different optical properties. The proposed method is purely based on elementary analytical benchmarks, therefore, the correctness of an MC code can be assessed with a one-sample t-test.Approach: The two-step verification is based on the following two analytical benchmarks: (1) the exact analytical formulas for the statistical moments of the spatial coordinates where the scattering events occur in an infinite medium and (2) the exact invariant solutions of the radiative transfer equation for radiance, fluence rate, and mean path length in media subjected to a Lambertian illumination.Results: We carried out a wide set of comparisons between MC results and the two analytical benchmarks for a wide range of optical properties (from non-scattering to highly scattering media, with different types of scattering functions) in an infinite non-absorbing medium (step 1) and in a non-absorbing slab (step 2). The deviations between MC results and exact analytical values are usually within two standard errors (i.e., t-tests not rejected at a 5% level of significance). The comparisons show that the accuracy of the verification increases with the number of simulated trajectories so that, in principle, an arbitrary accuracy can be obtained.Conclusions: Given the simplicity of the verification method proposed, we envision that it can be widely used in the field of biomedical optics.</p

Depth sensitivity of frequency domain optical measurements in diffusive media

The depth sensitivity functions for AC amplitude, phase (PH) and DC intensity signals have been obtained in the frequency domain (where the source amplitude is modulated at radio-frequencies) by making use of analytical solutions of the photon diffusion equation in an infinite slab geometry. Furthermore, solutions for the relative contrast of AC, PH and DC signals when a totally absorbing plane is placed at a fixed depth of the slab have also been obtained. The solutions have been validated by comparisons with gold standard Monte Carlo simulations. The obtained results show that the AC signal, for modulation frequencies < 200 MHz, has a depth sensitivity with similar characteristics to that of the continuous-wave (CW) domain (source modulation frequency of zero). Thus, the depth probed by such a signal can be estimated by using the formula of penetration depth for the CW domain (Sci. Rep. 6, 27057 (2016)). However, the PH signal has a different behavior compared to the CW domain, showing a larger depth sensitivity at shallow depths and a less steep relative contrast as a function of depth. These results mark a clear difference in term of depth sensitivity between AC and PH signals, and highlight the complexity of the estimation of the actual depth probed in tissue spectroscopy.Postprint (published version

Optimal estimation reconstruction of the optical properties of a two-layered tissue phantom from time-resolved single-distance measurements

In this work, we have tested the optimal estimation (OE) algorithm for the reconstruction of the optical properties of a two-layered liquid tissue phantom from time-resolved single-distance measurements. The OE allows a priori information, in particular on the range of variation of fit parameters, to be included. The purpose of the present investigations was to compare the performance of OE with the Levenberg–Marquardt method for a geometry and real experimental conditions typically used to reconstruct the optical properties of biological tissues such as muscle and brain. The absorption coefficient of the layers was varied in a range of values typical for biological tissues. The reconstructions performed demonstrate the substantial improvements achievable with the OE provided a priori information is available. We note the extreme reliability, robustness, and accuracy of the retrieved absorption coefficient of the second layer obtained with the OE that was found for up to six fit parameters, with an error in the retrieved values of less than 10%. A priori information on fit parameters and fixed forward model parameters clearly improves robustness and accuracy of the inversion procedure

Saturation of the lactate clearance mechanisms different from the "lactate shuttle" determines the anaerobic threshold: prediction from the bioenergetic model

It is demonstrated, that the bioenergetic model combined with the mathematical constraints determined by the experimental knowledge of the aerobic metabolism and the Lohmann reaction dictates the exact lactate (La)-time relationship during exercise. The theory predicts that La is necessarily produced (above the resting baseline), even during extremely low work loads, where the metabolism was usually considered in the past to be "pure" aerobic. The La rate of production increases linearly as a function of the work load. The anaerobic threshold is strictly determined by the saturation of the La clearance mechanisms of the body different from the "La shuttle" and not by the involvement of a sudden increased La production at the cellular level. These results imply that the half time of the PCr breakdown kinetics at the onset of a constant load exercise can be expressed as a function of the onset speed of the aerobic and of the anaerobic metabolism, even in the case of a very low mechanical power. The PCr half-time does not depend on the workload and represents a physiological invariant. The bioenergetic model was created during a long historical period, when it was believed that the La production was not present at all for very low exercise levels but, actually, the bioenergetic model predicts exactly the opposite result