Biomedical subjects

Alessandro Torricelli

Publications and source records attributed to Alessandro Torricelli.

At least 19 recordsLinked to original sources

PubMed2006

Absorption and scattering perturbations in homogeneous and layered diffusive media probed by time-resolved reflectance at null source-detector separation.

We characterize the capability of time-resolved reflectance measurements at small source-detector separation (less than 5 mm) to localize small inhomogeneities embedded in an otherwise homogeneous or layered diffusive medium. By considering both absorption and scattering inhomogeneities, we demonstrate the improvement of this approach in terms of contrast and spatial resolution, as compared to more typical set-ups involving larger source-detection separations (few centimeters). Simulations are performed exploiting an analytical perturbation approach to diffusion theory and a four-layer heterogeneous time-resolved Monte Carlo code, considering realistic tissue geometries. Exhaustive investigation in the parameters space is reported.

Absorption↗

PubMed2006

Modelling the balance between quiescence and cell death in normal and tumour cell populations.

When considering either human adult tissues (in vivo) or cell cultures (in vitro), cell number is regulated by the relationship between quiescent cells, proliferating cells, cell death and other controls of cell cycle duration. By formulating a mathematical description we see that even small alterations of this relationship may cause a non-growing population to start growing with doubling times characteristic of human tumours. Our model consists of two age structured partial differential equations for the proliferating and quiescent cell compartments. Model parameters are death rates from and transition rates between these compartments. The partial differential equations can be solved for the steady-age distributions, giving the distribution of the cells through the cell cycle, dependent on specific model parameter values. Appropriate formulas can then be derived for various population characteristic quantities such as labelling index, proliferation fraction, doubling time and potential doubling time of the cell population. Such characteristic quantities can be estimated experimentally, although with decreasing precision from in vitro, to in vivo experimental systems and to the clinic. The model can be used to investigate the effects of a single alteration of either quiescence or cell death control on the growth of the whole population and the non-trivial dependence of the doubling time and other observable quantities on particular underlying cell cycle scenarios of death and quiescence. The model indicates that tumour evolution in vivo is a sequence of steady-states, each characterised by particular death and quiescence rate functions. We suggest that a key passage of carcinogenesis is a loss of the communication between quiescence, death and cell cycle machineries, causing a defect in their precise, cell cycle dependent relationship.

Cell Cycle↗

PubMed2005

Time-resolved reflectance at null source-detector separation: improving contrast and resolution in diffuse optical imaging.

We propose a novel approach to imaging in diffusive media based on time-resolved reflectance measurements at null source-detector separation. This approach yields better spatial resolution and contrast as compared to the classical approach, which typically employs a separation of 20-40 mm. Results are obtained by an analytical perturbation approach to diffusion theory and on Monte Carlo simulations. Practical implementation with state-of-the-art technology and performance of a complementary approach based on the use of small but not null source-detector separation are also discussed.

Journal Article↗

PubMed2005

Dynamic time-resolved diffuse spectroscopy based on supercontinuum light pulses.

We present a detailed characterization of a system for fast time-resolved spectroscopy of turbid media based on supercontinuum generation in a photonic crystal fiber. The light source provides subpicosecond pulses in the 550-1000-nm spectral range, at 85 MHz, at an average power of up to 50 mW. Wavelength-resolved detection is accomplished by means of a spectrometer coupled to a 16-channel, multianode photomultiplier tube, giving a resolution of 4.5-35 nm/channel, depending on the grating. Time-dispersion curves are acquired with time-correlated single-photon counting, and absorption and reduced scattering coefficients are determined by fitting the data to the diffusion equation. We characterized the system by measuring the time-resolved diffuse reflectance of epoxy phantoms and by assessing the performance in terms of accuracy, linearity, noise sensitivity, stability, and reproducibility. The results were similar to those from previous systems, whereas the full-spectrum (610-810 nm) acquisition time was as short as 1 s owing to the parallel acquisition. We also present the first in vivo real-time dynamic spectral measurements showing tissue oxygenation changes in the arm of a human subject.

Algorithms↗

PubMed2005

Time-resolved optical mammography between 637 and 985 nm: clinical study on the detection and identification of breast lesions.

The first time-resolved optical mammograph operating beyond 900 nm was tested in a retrospective clinical study involving 194 patients with malignant and benign lesions, to investigate the diagnostic potential for the detection and characterization of breast lesions. For the first part of the study (101 patients with 114 lesions), the system was operated at 683, 785, 913 and 975 nm. Subsequently, to improve the spectral content of optical images, the number of wavelengths was increased (up to 7) and the spectral range was extended (637-985 nm). Late gated intensity and scattering images provide sensitivity to tissue composition (oxy- and deoxyhaemoglobin, water and lipids) and physiology (total haemoglobin content and oxygen saturation), as well as to structural changes. Tumours are typically identified because of the strong blood absorption at short wavelengths (637-685 nm), while cysts are characterized by low scattering, leading to a detection rate of approximately 80% for both lesion types, when detection is required in both cranio-caudal and oblique views. The detection rate for other benign lesions, such as fibroadenomas, is presently much lower (<40%). The effectiveness of the technique in localizing and identifying different lesion types was analysed as a function of various parameters (lesion size, compressed breast thickness, age, body mass index, breast parenchymal pattern). The possibility that physiologic changes due to the development of a malignant lesion could affect the entire breast was investigated. The capacity to assess the density of breast based on the average scattering properties was also tested.

Breast Cyst↗

PubMed2005

Characterization of female breast lesions from multi-wavelength time-resolved optical mammography.

Characterization of both malignant and benign lesions in the female breast is presented as the result of a clinical study that involved more than 190 subjects in the framework of the OPTIMAMM European project. All the subjects underwent optical mammography, by means of a multi-wavelength time-resolved mammograph, in the range 637-985 nm. Optical images were processed by applying a perturbation model, relying on a nonlinear approximation of time-resolved transmittance curves in the presence of an inclusion, with the aim of estimating the major tissue constituents (i.e. oxy- and deoxy-haemoglobin, lipid and water) and structural parameters (linked to dimension and density of the scatterer centres) for both the lesion area and the surrounding tissue. The critical factors for the application of the perturbation model on in vivo data are also discussed. Forty-six malignant and 68 benign lesions were analysed. A subset of 32 cancers, 40 cysts and 14 fibroadenomas were found reliable for the perturbation analysis. For cancers, we show a higher blood content with respect to the surrounding tissue, while cysts are characterized by a lower concentration of scattering centres with respect to the surrounding tissue. For fibroadenomas, the low number of cases does not allow any definite conclusions.

Breast Cyst↗

PubMed2005

Characterization of normal breast tissue heterogeneity using time-resolved near-infrared spectroscopy.

In recent years, extensive efforts have been made in developing near-infrared optical techniques to be used in detection and diagnosis of breast cancer. Variations in optical properties of normal breast tissue set limits to the performance of such techniques and must therefore be thoroughly examined. In this paper, we present intra- and intersubject as well as contralateral variations of optical and physiological properties in breast tissue as measured by using four-wavelength time-resolved spectroscopy (at 660, 786, 916 and 974 nm). In total, 36 volunteers were examined at five regions at each breast. Optical properties (absorption, mu(a), and reduced scattering, mu'(s)) are derived by employing diffusion theory. The use of four wavelengths enables determination of main tissue chromophores (haemoglobin, water and lipids) as well as haemoglobin oxygenation. Variations in all evaluated properties seen over the entire breast are approximately twice those for small-scale heterogeneity (millimetre scale). Intrasubject variations in optical properties are almost in all cases below 20% for mu'(s), and 40% for mu(a). Overall variations in water, lipid and haemoglobin concentrations are all in the order of 20%. Oxygenation is the least variable of the quantities evaluated, overall intrasubject variations being 6% on average. Extracted physiological properties confirm differences between pre- and post-menopausal breast tissue. Results do not indicate systematic differences between left and right breasts.

Adult↗

PubMed2005

Performance assessment of photon migration instruments: the MEDPHOT protocol.

We propose a comprehensive protocol for the performance assessment of photon migration instruments. The protocol has been developed within the European Thematic Network MEDPHOT (optical methods for medical diagnosis and monitoring of diseases) and is based on five criteria: accuracy, linearity, noise, stability, and reproducibility. This protocol was applied to a total of 8 instruments with a set of 32 phantoms, covering a wide range of optical properties.

Benchmarking↗

PubMed2004

Time-resolved spectrophotometer for turbid media based on supercontinuum generation in a photonic crystal fiber.

We describe an instrument for the time-resolved spectroscopy of turbid media that is based on supercontinuum generation in a photonic crystal fiber. The light injected into the sample consists of subpicosecond pulses that cover 550-1000 nm at 85 MHz at an average power of as much as 40 mW. A spectrometer coupled to a multianode photomultiplier tube is used to detect the light simultaneously in 16 wavelength channels, with a resolution of 5-20 nm/channel, depending on the grating. Time-correlated single-photon counting is used to produce time-dispersion curves, which one fits to the diffusion equation to determine absorption and reduced scattering coefficients. We tested the instrument by measuring the time-resolved diffuse reflectance of epoxy phantoms and by performing in vivo measurements on volunteers. The results were similar to those obtained with previous discrete wavelength systems, whereas the full spectrum (610-810 nm) acquisition time was as short as 1 s owing to the parallel acquisition.

Abdomen↗

PubMed2004

Phantom validation and in vivo application of an inversion procedure for retrieving the optical properties of diffusive layered media from time-resolved reflectance measurements.

An experimental validation of an inversion procedure for retrieving the optical properties of layered media from multidistance time-resolved reflectance measurements is presented. The results cover a wide range of optical properties, showing excellent effectiveness and reliability of the procedure in reconstructing the optical properties of a two-layered medium. The optical properties of the first layer and the absorption of the second layer could be retrieved with excellent precision, whereas the reduced scattering coefficient of the second layer was reconstructed with a large error. The first layer thickness could be retrieved with an error less than 50%. An example of retrieval of the optical properties of muscle from in vivo measurements during an arterial occlusion is shown.

Algorithms↗

PubMed2004

Mapping of calf muscle oxygenation and haemoglobin content during dynamic plantar flexion exercise by multi-channel time-resolved near-infrared spectroscopy.

A compact and fast multi-channel time-resolved near-infrared spectroscopy system for tissue oximetry was developed. It employs semiconductor laser and fibre optics for delivery of optical signals. Photons are collected by eight 1 mm fibres and detected by a multianode photomultiplier. A time-correlated single photon counting board is used for the parallel acquisition of time-resolved reflectance curves. Estimate of the reduced scattering coefficient is achieved by fitting with a standard model of diffusion theory, while the modified Lambert-Beer law is used to assess the absorption coefficient. In vivo measurements were performed on five healthy volunteers to monitor spatial changes in calf muscle (medial and lateral gastrocnemius; MG, LG) oxygen saturation (SmO2) and total haemoglobin concentration (tHb) during dynamic plantar flexion exercise performed at 50% of the maximal voluntary contraction. At rest SmO2 was 73.0 +/- 0.9 and 70.5 +/- 1.7% in MG and LG, respectively (P = 0.045). At the end of the exercise, SmO2 decreased (69.1 +/- 1.8 and 63.8 +/- 2.1% in MG and LG, respectively; P < 0.01). The LG desaturation was greater than the MG desaturation (P < 0.02). These results strengthen the role of time-resolved near-infrared spectroscopy as a powerful tool for investigating the spatial and temporal features of muscle SmO2 and tHb.

Adipose Tissue↗

PubMed2003

Four-wavelength time-resolved optical mammography in the 680-980-nm range.

What is to our knowledge the first instrument for time-resolved optical mammography operating at wave-lengths longer than 900 nm has been developed. It is a scanning system that relies on the acquisition of time-resolved transmittance curves at 683, 785, 912, and 975 nm, with a total measurement time of approximately 5 min for an entire image. Breast structures and lesions can be discriminated based on the different absorption and scattering properties at the four wavelengths, which reflect different contributions of oxyhemoglobin, deoxyhemoglobin, water, and lipids, as well as distinct structures. The system is currently used in a European clinical trial.

Breast↗

PubMed2003

Experimental test of a perturbation model for time-resolved imaging in diffusive media.

We report what to our knowledge is a novel perturbation approach for time-resolved transmittance imaging in diffusive media, based on the diffusion approximation with extrapolated boundary conditions. The model relies on the method of Padé approximants and consists of a nonlinear approximation of time-resolved transmittance curves in the presence of an inclusion. The proposed model is intended to extend the range of applicability of perturbation models when applied to inclusions that are non-point-like. We test the model on different tissue phantoms with scattering only, absorbing only, and both scattering and absorbing inclusions. Maps of the optical properties are displayed, and the results are compared with those obtained by means of the usual linear approximation of time-resolved transmittance curves. We found that the nonlinear approach gives a better prediction for absolute values of the scattering and absorption coefficients of inclusions, when the inclusion optical properties are higher than the surrounding background. Furthermore, better-resolved spots and a reduced cross talk between the two parameters are found in the reconstructed maps. Because the range of the optical properties spanned by the considered phantoms covers the values expected for optical mammography, the application of the reported reconstruction method to in vivo images of a breast appears promising from a diagnostic viewpoint.

Biological Phenomena↗

PubMed2003

In vivo absorption and scattering spectroscopy of biological tissues.

Different approaches for absorption and scattering spectroscopy of living tissues are discussed. In particular, a unique system for time-resolved reflectance and transmittance spectroscopy is presented, capable of acquiring in vivo absorption and scattering spectra of diffusive media between 600 and 1000 nm. A review of typical spectra obtained from a variety of tissue structures is shown, including female breast, forearm, abdomen, and forehead. A second-level analysis of the measured spectra permits an estimation of the concentrations of the key tissue absorbers, as well as of the Mie-equivalent scattering radii. Further, absorption and scattering spectra can be used to estimate the penetration depth of light in tissues as a function of wavelength, which is a crucial parameter in view of the possible application of optical in vivo molecular imaging in clinical diagnosis. Finally, an example of the applicability of the methodology to other biological media such as fruits and vegetables is shown.

Abdomen↗

PubMedDate not supplied

Optical biopsy of bone tissue: a step toward the diagnosis of bone pathologies.

In vivo absorption and reduced scattering spectra of the human calcaneous from 650 to 1000 nm were assessed using a laboratory system for time-resolved transmittance spectroscopy. Measurements were performed on the calcaneous of seven female volunteers ranging from 26 to 82 years of age. The analysis of the absorption spectra, using a linear combination of the key tissue absorbers (bone mineral, water, lipids, oxy- and deoxyhemoglobin), revealed a general decrease in bone mineral content and an increase in lipids with age, which is in agreement with the aging transformations that occur in bone tissues. The scattering spectra were less effective in detecting such changes in older subjects, showing only a minor decrease in the coefficient for these subjects. The capability to noninvasively quantify bone tissue composition suggests a possible use of optical biopsy for the diagnosis of bone pathologies such as osteoporosis, which are characterized by a progressive reduction and transformation of the mineral in the bone matrix.

Adult↗

PubMedDate not supplied

Clinical trial of time-resolved scanning optical mammography at 4 wavelengths between 683 and 975 nm.

The first time-resolved optical mammograph operating beyond 900 nm (683, 785, 913, and 975 nm) is presently being used in a clinical trial to test the diagnostic potential of the technique in detecting and characterizing breast lesions. Between November 2001 and October 2002, 101 patients with malignant and benign lesions were analyzed retrospectively. Scattering plots, as derived from a homogeneous model, and late gated intensity images, to monitor spatial changes in the absorption properties, are routinely used. The intensity images available at four wavelengths provide sensitivity to the main tissue constituents (oxy- and deoxyhemoglobin, water, and lipids), in agreement with expected tissue composition and physiology, while the scattering plots mirror structural changes. Briefly, tumors are usually identified due to the strong blood absorption at short wavelengths, cysts to the low scattering, and fibroadenomas to low absorption at 913 nm and high at 975 nm, even though the optical features of fibroadenomas seem not to be uniquely defined. The effectiveness of the technique in localizing and discriminating different lesion types is analyzed as a function of various parameters (lesion size, compressed breast thickness, and breast parenchymal pattern). .

Algorithms↗

PubMedDate not supplied

Spectroscopic time-resolved diffuse reflectance and transmittance measurements of the female breast at different interfiber distances.

The first, to our knowledge, in-vivo broadband spectroscopic characterization of breast tissue using different interfiber distances as well as transmittance measurements is presented. Absorption and scattering properties are measured on six healthy subjects, using time-resolved diffuse spectroscopy and an inverse model based on the diffusion equation. Wavelength-tunable picosecond-pulse lasers and time-correlated single-photon counting detection are employed, enabling fully spectroscopic measurements in the range 610 to 1040 nm. Characterization of the absorption and reduced scattering coefficients of breast tissue is made with the aim of investigating individual variations, as well as variations due to different measurement geometries. Diffuse reflectance measurements at different interfiber distances (2, 3, and 4 cm) are performed, as well as measurements in transmittance mode, meaning that different sampling volumes are involved. The results show a large variation in the absorption and scattering properties depending on the subject, correlating mainly with the water versus lipid content of the breast. Intrasubject variations, due to different interfiber distances or transmittance modes, correlate with the known structures of the breast, but these variations are small compared to the subject-to-subject variation. The intrasubject variations are larger for the scattering data than the absorption data; this is consistent with different spatial localization of the measurements of these parameters, which is explained by the photon migration theory.

Adult↗

PubMedDate not supplied

Bulk optical properties and tissue components in the female breast from multiwavelength time-resolved optical mammography.

We present the results of a clinical study about optical properties and bulk composition of the female breast. The clinical study involved more than 150 subjects that underwent optical mammography. A multiwavelength time-resolved mammograph designed to collect time-resolved transmittance images of the breast at different wavelengths in the range 637 to 980 nm is used to this purpose. From the absorption spectrum of the breast, the concentrations of the main tissue constituents, i.e., oxygenated and deoxygenated hemoglobin, lipid, and water, are obtained for a subset of 113 breasts. The lipid content of breast is estimated for the first time on such a large number of subjects. The total hemoglobin concentration, blood oxygen saturation, lipid, and water content of breast is correlated to demographic information collected during the trial. As expected, breast optical properties and components undergo huge variations among different subjects. Different constituents, however, show interesting correlation with clinical parameters such as age, breast size, body mass index, and mammographic parenchymal pattern. These results suggest that optical measurements on breasts can be exploited to obtain relevant information on breast tissue composition.

Breast↗