Biomedical subjects

Lorenzo Spinelli

Publications and source records attributed to Lorenzo Spinelli.

13 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

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

Localization and quantification of fluorescent inclusions embedded in a turbid medium.

A set-up, based on a CCD camera, to localize fluorescent inclusions in diffusing media was developed. This set-up allows one to acquire a huge dataset along two axes. This aspect is fundamental to performing a tomographic reconstruction in order to quantify the fluorescence amplitude in each voxel of the sample. Firstly, a simple analytical approach to recover the position of a single inclusion, embedded in a turbid medium, was developed. Then, we implemented a reconstruction algorithm to recover the position of one and two inclusions and to estimate their relative concentrations. Finally, we studied the dependence of reconstructed data on the number of injection points of excitation light and the number of detection points of fluorescence emission.

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

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↗

PubMed2002

Cavity solitons as pixels in semiconductor microcavities.

Cavity solitons are localized intensity peaks that can form in a homogeneous background of radiation. They are generated by shining laser pulses into optical cavities that contain a nonlinear medium driven by a coherent field (holding beam). The ability to switch cavity solitons on and off and to control their location and motion by applying laser pulses makes them interesting as potential 'pixels' for reconfigurable arrays or all-optical processing units. Theoretical work on cavity solitons has stimulated a variety of experiments in macroscopic cavities and in systems with optical feedback. But for practical devices, it is desirable to generate cavity solitons in semiconductor structures, which would allow fast response and miniaturization. The existence of cavity solitons in semiconductor microcavities has been predicted theoretically, and precursors of cavity solitons have been observed, but clear experimental realization has been hindered by boundary-dependence of the resulting optical patterns-cavity solitons should be self-confined. Here we demonstrate the generation of cavity solitons in vertical cavity semiconductor microresonators that are electrically pumped above transparency but slightly below lasing threshold. We show that the generated optical spots can be written, erased and manipulated as objects independent of each other and of the boundary. Numerical simulations allow for a clearer interpretation of experimental results.

Journal Article↗

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

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↗

PubMedDate not supplied

Bilateral prefrontal cortex oxygenation responses to a verbal fluency task: a multichannel time-resolved near-infrared topography study.

The letter-fluency task-induced response over the prefrontal cortex is investigated bilaterally on eight subjects using a recently developed compact, eight-channel, time-resolved, near-IR system. The cross-subject mean values of prefrontal cortex oxygen saturation (SO2) were 68.8+/-3.2% (right) and 71.0+/-3.6% (left), and of total hemoglobin concentration (tHb) were 69.6+/-9.6 microM (right) and 69.5+/-9.9 microM (left). The typical cortical activation response to the cognitive task [characterized by an increase in oxyhemoglobin (O2Hb) with a concurrent decrease in deoxyhemoglobin (HHb)] at each measurement point is observed in only four subjects. In this subset, the amplitude of the O2Hb increase and HHb decrease is uniform over each prefrontal cortex area and comparable between the two hemispheres. These findings agree with previous studies using continuous wave functional near-IR spectroscopy and functional magnetic resonance imaging, therefore demonstrating the potential of a time-resolved spectroscopy approach. In addition, a significant increase in SO2 levels was observed in the right (1.1+/-0.5%) compared to left side of the prefrontal cortex (0.9+/-0.5%) (P=0.005). A different pattern of cortical activation (characterized by the lack of HHb decrease or even increased HHb) was observed in the remaining subjects.

Adult↗

PubMedDate not supplied

Feasibility of white-light time-resolved optical mammography.

We demonstrate the feasibility of white-light time-resolved optical mammography. The instrumentation is based on supercontinuum light generated in photonic crystal fiber and 32-channel parallel time-correlated single-photon-counting detection. Total measurement time is of the order of 10 min for typical clinical applications. Preliminary measurements performed on volunteers show the ability of the system to determine tissue constituent concentrations and structure over the entire breast area. Furthermore, measurements on a tissue-like sample demonstrate detection and characterization of inclusions.

Adult↗