Tiziano Binzoni

• University of Geneva

The exact homogenized probability density function, for a photon making a step of length s has been analytically derived for a binary (isotropic-Poisson) statistical mixture with unmatched refractive indexes. The companions, exact, homogenized probability density functions for a photon to change direction (“scatter”), with polar ϑ and azimuthal φ a...

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 stat...

Anomalous radiative transfer (ART) theory represents a generalization of classical radiative transfer theory. The present tutorial aims to show how Monte Carlo (MC) codes describing the transport of photons in anomalous media can be implemented. We show that the heart of the method involves suitably describing, in a “non-classical” manner, photon s...

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...

Anomalous radiative transfer (ART) theory is a generalization of classical radiative transfer theory. The present tutorial wants to show how Monte Carlo (MC) codes describing photons transport in anomalous media can be implemented. It is shown that the heart of the method consists in suitably describing, in a "non-classical" manner, photons steps s...

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 se...

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 set...

In this paper, we derive some explicit analytical solutions to the equations for the slab geometry that is illuminated by a collimated plane source. The resulting expressions for the total reflectance and transmittance are compared with the corresponding transport theory solution predicted by the Monte Carlo method. Further, for the special case of...

A generalized time-independent correlation transport equation (GCTE) is proposed for the field autocorrelation function. The GCTE generalizes various models for anomalous transport of photons and takes into account the possible presence of a static background. In a tutorial example, the GCTE is solved for a homogeneous semi-infinite medium in refle...

We present a time domain diffuse Raman spectrometer for depth probing of highly scattering media. The system is based on, to the best of our knowledge, a novel time-correlated single-photon counting (TCSPC) camera that simultaneously acquires both spectral and temporal information of Raman photons. A dedicated non-contact probe was built, and time...

An heuristic model for ballistic photon detection in continuous-wave measurements of collimated transmittance through a slab is presented. The model is based on the small angle approximation and the diffusion equation and covers all the ranges of optical thicknesses of the slab from the ballistic to the diffusive regime. The performances of the mod...

In the present contribution, the theoretical relationship existing between the blood flow index measured by diffuse correlation spectroscopy and single-photon laser-Doppler flowmetry (SP-LDF) is investigated. A specific mathematical description that accounts for the properties of single-photon detectors for SP-LDP was developed. Static background h...

In this work an analytical model for the time-resolved signal emitted by a uniformly distributed Raman scatterer in a diffusive parallelepiped is derived and validated with Monte Carlo (MC) simulations.

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, P...

A new correlation diffusion equation has been derived from a correlation transport equation allowing one to take into account the presence of moving scatterers and static background. Solutions for the reflectance from a semi-infinite medium have been obtained (point-like and ring detectors). The solutions have been tested by comparisons with “gold...

The correlation transport equation (CTE) is the natural generalization of the theory for diffusion correlation spectroscopy and represents a more precise model when dealing with measurements of particle movement in fluids or red blood cell flow in biological tissues. Unfortunately, the CTE is not methodically used due to the complexity of finding s...

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 a...

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,...

Diffuse correlation spectroscopy (DCS) is the technique of choice for non-invasive assessments of human bone blood flow. However, DCS classical algorithms are based on the fundamental assumption that the electric field of the light reaching the DCS photodetector is a zero-mean complex Gaussian variable. The non-validity of this hypothesis might pro...

We propose a comprehensive statistical approach for the calculation of the light penetration depth in diffusive media, both in continuous-wave and time-domain regimes. Analytical results are validated with Monte-Carlo simulations.

In this work an analytical model for the time-resolved Raman scattering signal coming from a homogeneous diffusive parallelepiped is derived and validated with Monte Carlo (MC) simulations.

We robustly and accurately estimated the absorption coefficient of the second layer in a two-layer tissue phantom by applying an optimal estimation method, including a priori information, to single-distance time-resolved 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 investig...

The study of bone blood flow regulation in humans has always represented a difficult task for the clinician and the researcher. Classical measurement techniques imply the presence of ionizing radiation or contrast agents, or they are slow or cannot be repeated too often in time. In the present review, we would like to give a perspective on how the...

It is shown that an analytical noise-free implementation of Monte Carlo simulations [Appl. Opt. 54, 2400 (2015)10.1364/AO.54.002400APOPAI1559-128X] for diffuse correlation spectroscopy (DCS) may be successfully used to check the ability of a given DCS model to generate a reliable estimator of tissue blood flow. As an example, four different DCS mod...

Classical Monte Carlo (MC) simulations for laser-Doppler flowmetry (LDF) often necessitate too long computation times and specialized hardware. This is particularly true for LDF at large interoptode spacing with low absorption coefficients and large anisotropic factors representing real biological tissues. For this reason, a random numbers free “an...

The classical reciprocity relation of radiative transfer fails for two points placed in regions having different indices of refraction. A modified reciprocity relation that involves the relative refractive index between the two points considered was previously derived for the continuous wave (cw) radiative transfer equation and for the cw diffusion...

A new laser-Doppler flowmeter at large interoptode spacing, based on single-photon counting (single-photon laser-Doppler flowmetry [SP-LDF]) and allowing assessment of blood flow deep in bone tissue, is proposed and implemented. To exploit the advantages of the new SP-LDF hardware, a dedicated simple and efficient time-domain algorithm has been dev...

A bone tissue phantom prototype allowing to test, in general, optical flowmeters at large interoptode spacings, such as laser-Doppler flowmetry or diffuse correlation spectroscopy, has been developed by 3D-stereolithography technique. It has been demonstrated that complex tissue vascular systems of any geometrical shape can be conceived. Absorption...

Analytical models, describing laser Doppler flowmetry and its derived applications, are based on fundamental assumptions of photon scattering angles. It is shown by means of Monte Carlo simulations that, even in the case these assumptions are correct, the presence of a specific source–detector configuration may bias the shape of the probability den...

The cardiac cycle related pulsatile behavior of the absorption and scattering coefficients of diffuse light and the corresponding alterations in hemoglobin concentrations in the human patella was studied. The pulsations in scattering is considerably smaller than absorption. The difference in amplitude of absorption coefficient pulsations for differ...

Human bone blood flow, mean blood speed and the number of moving red blood cells were assessed (in arbitrary units), as a function of time, during one cardiac cycle. The measurements were obtained non-invasively on five volunteers by laser-Doppler flowmetry at large interoptode spacing. The investigated bones included: patella, clavicle, tibial dia...

Laser Doppler flowmetry (LDF) and laser speckle contrast imaging (LSCI) allow the monitoring of microvascular blood perfusion. The relationship between the measurements obtained by these two techniques remains unclear. In the present contribution we demonstrate, experimentally and theoretically, that skin blood flow measurements obtained by LDF and...

Using a small, but very instructive experiment, it is demonstrated that laser-Doppler flowmetry (LDF) at large interoptode spacing represents a unique tool for new investigations of thermoregulatory processes modulating the blood flow of small muscle masses in humans. It is shown on five healthy subjects that steady-state values of blood flow (perf...

Pulsatile and static hemodynamics of the human patella (knee-cap) were studied at rest and at arterial cuff-occlusion. Differences in hemodynamics between the patella and the muscle were observed.

Laser-Doppler flowmetry (LDF) is an outstanding tool to monitor blood flow in a continuous and non-invasive way. In this work, we study LDF at large interoptode spacing applied to a human bone model (i.e. tibia diaphysis). To that aim, we first performed an extensive set of Monte Carlo (MC) simulations for 10 and 25 mm interoptode spacing. Second,...

Understanding the mechanisms of interaction between bone/bone marrow, circulatory system and nervous system is of great interest due to the potential clinical impact. In humans, the amount of knowledge in this domain remains relatively limited due to the extreme difficulty to monitor these tissues continuously, noninvasively and for long or repeate...

A new approach to measure muscle oxygen saturation (SmO(2)) using near infrared spectroscopy (NIRS) has been proposed in this paper. This approach exploits the cyclic NIRS signals seen during exercise which are often regarded as "movement artefacts". This new measure, which we term the "cyclic SmO(2)", has the potential to be less affected by the m...

Near infrared spectroscopy (NIRS) can readily report on changes in blood volume and oxygenation. However, it has proved more problematic to measure real-time changes in blood flow and oxygen consumption. Here we report the development of a novel method using NIRS to measure local oxygen consumption in human muscle. The method utilizes the blood vol...

In this study, we derive a fast, novel time-domain algorithm to compute the nth-order moment of the power spectral density of the photoelectric current as measured in laser-Doppler flowmetry (LDF). It is well established that in the LDF literature these moments are closely related to fundamental physiological parameters, i.e. concentration of movin...

A new approach to measure muscle oxygen saturation (SmO2) using near infrared spectroscopy (NIRS) has been proposed in this paper. This approach exploits the cyclic NIRS signals seen during exercise which are often regarded as "movement artefacts". This new measure, which we term the "cyclic SmO2", has the potential to be less affected by the myogl...

Monte Carlo (MC) simulations significantly contributed to a better understanding of laser-Doppler flowmetry (LDF). Here it is shown that the data obtained from standard MC simulations can be reinterpreted and used to extract more information such as the photo-electric current (i(t)). This is important because i(t) is the starting point for evaluati...

Using Monte Carlo simulations for a semi-infinite medium representing a skeletal muscle tissue, it is demonstrated that the zero- and first-order moments of the power spectrum for a representative pixel of a full-field laser-Doppler imager behave differently from classical laser-Doppler flowmetry. In particular, the zero-order moment has a very low...

The present work shows that the optical/biological information contained in a typical spectral image mainly reflects the properties of a small (conic like) volume of tissue situated vertically under each individual pixel. The objects appearing on a spectral image reasonably reproduce the correct geometrical shape and size (like a non-deformed shado...

Monte Carlo (MC) based simulations of photon transport in living tissues have become the "gold standard" technique in biomedical optics. Three-dimensional (3D) voxel-based images are the natural way to represent human (and animal) tissues. It is generally believed that the combination of 3D images and MC based algorithms allows one to produce the m...

In this letter the authors highlight the presence of an error appearing in the discussion of the note 'The use of the Henyey-Greenstein phase function in Monte Carlo simulations in biomedical optics' previously published by them (Binzoni et al 2006 Phys. Med. Biol. 51 N313). In the light of this error, the discussion and conclusions in the original...

Monte Carlo (MC) simulations are often at the heart of the testing procedure in biomedical optics. One of the critical points in MC simulations is to define the new photon direction after each scattering event. One of the most popular solutions is to use the Henyey-Greenstein phase function or some linear combinations of it. In this note, we demons...

It is demonstrated in the short head of the human biceps brachii of 16 healthy subjects (12 males and 4 females) that near infrared photon migration is anisotropic. The probability for a photon to travel along the direction of the muscle fibres is higher (approximately 0.4) than that of travelling along a perpendicular axis (approximately 0.3) whil...

The interest in, and the need for effective measures to be used in screening, diagnosis, and the follow-up of skeletal pathologies is growing markedly. This paper proposes a completely new and non-invasive technique allowing the study of the human tibia bone marrow (BM) haemodynamics with a time resolution of 1 s. The technique, based on near infra...

Based on quasi-elastic scattering theory (and random walk on a lattice approach), a model of laser-Doppler flowmetry (LDF) has been derived which can be applied to measurements in large tissue volumes (e.g. when the interoptode distance is >30 mm). The model holds for a semi-infinite medium and takes into account the transport-corrected scattering...

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 extrem...

This study reports the derivation of a precise mathematical relationship existing between the different p-moments of the power spectrum of the photoelectric current, obtained from a laser-Doppler flowmeter (LDF), and the red blood cell speed. The main purpose is that both the Brownian (defining the 'biological zero') and the translational movements...

A new method of thermoablation with hot water vapour based on a new type of microtube was developed. This approach allows tumours, with volume and anatomical positions not accessible to other techniques (cryoablation, radiofrequency ablation, laser ablation) to be treated. The method was tested on a human colon carcinoma grafted subcutaneously in S...

Near-infrared spectroscopy (NIRS) and laser Doppler flowmetry (LDF) have become the techniques of choice allowing the non-invasive study of local human skeletal muscle metabolism and blood perfusion on a small tissue volume (a few cm3). However, it has been shown that both NIRS and LDF measurements may show a large spatial variability depending on...

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 (Uber die Erhaltung der Kraft, 1847) showed that the principle of energy conservation may be applied to living systems. In the field of exercise physiology, th...

A human model allowing the non-invasive study of bone marrow haemodynamics has been developed. A decrease in postischaemic tissue reperfusion capability (postischaemic hyperaemia) as a function of age (range 25-72 years) was observed both in the human tibia and tibialis anterior muscle. In the tibia bone marrow the reperfusion capability started to...

This study proposes the implementation of an algorithm allowing one to derive absolute blood root-mean-square (RMS) velocity values from laser Doppler perfusion meter (LDP) data. The algorithm is based on the quasi-elastic light scattering theory and holds for multiple scattering. While standard LDP measurements are normally applicable to a small r...

A minimally invasive technique based on a new type of microtube was developed. This approach should allow the treament of tumours, which volume and anatomical position are not accessible to other techniques available (cryoablation, radiofrequency ablation, laser, etc). The active agent is delivered under high pressure. In this work, the efficacy of...

Heat-up tilting manoeuvre from 0 to 60 degrees induces oxygenated and deoxygenated haemoglobin concentration changes in the human gastrocnemius. These changes, measured by NIRS, can only be partially explained by the blood volume displacement due to the gravitational force. In the present study it is demonstrated, by a dye dilution technique (indoc...

Human tibia bone marrow (BM) and tibialis anterior muscle (TA) perfusion index (PI) was assessed non-invasively by near infrared spectroscopy. A decrease in the postis-chaemic reperfusion capability of the human tibia BM and TA muscle was observed for increasing age i.e., PI increases linearly as a function of age, starting from 30 years, both for...

The present work was aimed at measuring intramuscular oxygen consumption (O(2)) as a function of temperature (T), in human forearm, during rest and aerobic isometric exercise (4% of the maximal voluntary contraction, MVC). Based upon results from in vitro experiments performed on isolated mitochondria of animal species, it was hypothesised that, du...

The age dependence of human gastrocnemius Mg2+ concentration is demonstrated. To quantitate Mg2+ concentration, an original and accurate fitting algorithm using quantum mechanics-based prior knowledge is detailed. In a group of 28 volunteers (14 females) in the age range 5-80 years, pH, PCr/ATP and Pi/ATP values in the gastrocnemius were 7.02 +/- 0...

The aim of the present study was to quantify changes in human skeletal muscle pennation angle (F theta) values during growth and adult life. The human gastrocnemius medialis muscle of 162 subjects (96 males and 66 females) in the age range 0-70 years was scanned with ultrasonography. The subjects were laying prone, at rest, with the ankle maintaine...

The aim of this review is to describe the effects induced by local temperature changes on human skeletal muscle metabolism. More specifically, we will consider the influence of temperature on the mechanical properties of muscle contraction, on aerobic metabolism, anaerobic metabolism and on the Lohmann reaction. The text has been voluntarily organi...

We propose the use of near-infrared spectroscopy (NIRS) to monitor neonatal brain temperature non-invasively and continuously during hypothermic treatment by measuring changes in the NIR water absorption spectrum. Accurate measurements of the water spectrum in the range 650-1050 nm between 42 and 32 °C have been made and calibrated using a principa...

It is well established that ADP is an important regulator of the oxidative phosphorylation in the mitochondria. Thus, by means of noninvasive techniques it is demonstrated that the relationship between O(2) consumption of the human gastrocnemius at rest and its temperature is likely determined by at least two factors: 1) the modulation of the rate...

The purpose of this study is to develop a new method for the measurement in humans of the compliance of the microvascular superficial venous system of the lower limb by near-infrared spectroscopy (NIRS). This method is complementary to strain-gauge plethysmography, which does not allow compliance between deep and superficial venous or between venou...

In the past, the measurement of O(2) consumption ((2)) by the muscle could be carried out noninvasively by near-infrared spectroscopy from oxyhemoglobin and/or deoxyhemoglobin measurements only at rest or during steady isometric contractions. In the present study, a mathematical model is developed allowing calculation, together with steady-state le...

Temperature modulates tissue metabolism through thermodynamic phenomena, e.g. changes in enzymatic activities, pH variations, etc. In humans, temperature changes may be induced by stressful environmental conditions (e.g. immersion in cold water, etc.) or, artificially, during therapeutic procedures (extracorporeal circulation, cancer treatment usin...

Energy metabolism and interstitial fluid displacement were studied in the human gastrocnemius during three subsequent 5-min ischemia-reperfusion periods [ischemic preconditioning (IP)]. The muscle energy balance was assessed by combining near-infrared spectroscopy (NIRS) and 31P-nuclear magnetic resonance spectroscopy (31P-NMRS). The interstitial f...

In the last decade the study of the human muscle mechanics and energetics in physiology and pathology underwent a radical change. Indeed, the use of biopsy is being progressively accompanied by non-invasive techniques which allow a more integrative assessment of muscle function in vivo. Magnetic resonance imaging (MRI) provides a better insight int...

Oxidative metabolism is the dominant source of energy for skeletal muscle. Near-infrared spectroscopy allows the non-invasive measurement of local oxygenation, blood flow and oxygen consumption. Although several muscle studies have been made using various near-infrared optical techniques, it is still difficult to interpret the local muscle metaboli...

It is well known that the VO2 readjustment rate of the whole body is faster when carrying out a given constant work load starting from a baseline of moderate exercise than from rest. However, it has not been established whether the above change is the result of faster kinetics of the oxidative machinery or, alternatively, the consequence of a reduc...

Ischaemic preconditioning (IP) (Lawson & Downey, 1993) with one or more cycles, consisting each of a short period of ischaemia followed by equal periods of reperfusion, improves myocardial tolerance to a subsequent ischaemic stress under experimental (Przyklenk et al., 1994) and clinical (Yellon et al., 1993) conditions. It has also been shown in r...

The authors investigated the usefulness of dynamic phosphorus-31 magnetic resonance (MR) spectroscopy in the assessment of hepatic function by studying the effect of a fructose load on a rat model of liver cirrhosis. In vivo P-31 MR liver spectra of eight rats with bile duct ligature and 10 control rats were obtained every 4.6 minutes before and af...

1. Human gastrocnemius medialis architecture was analysed in vivo, by ultrasonography, as a function of joint angle at rest and during voluntary isometric contractions up to the maximum force (MCV). maximum force (MVC). 2. At rest, as ankle joint angle increased from 90 to 150 deg, pennation increased from 15.8 to 27.7 deg, fibre length decreased f...

1. The recently isolated compound methyllycaconitine (MLA) is a plant toxin which is a competitive inhibitor of nicotinic acetylcholine receptors (nAChRs). We found that homomeric alpha 7 receptors display a very high sensitivity to MLA with an IC50 in the picomolar range. 2. The competitive nature of the alpha 7 MLA blockade was reinforced by the...