Biomedical subjects

Fabrizio Martelli

Publications and source records attributed to Fabrizio Martelli.

17 recordsLinked to original sources

PubMed2006

The hypomorphic Gata1low mutation alters the proliferation/differentiation potential of the common megakaryocytic-erythroid progenitor.

Recent evidence suggests that mutations in the Gata1 gene may alter the proliferation/differentiation potential of hemopoietic progenitors. By single-cell cloning and sequential replating experiments of prospectively isolated progenitor cells, we demonstrate here that the hypomorphic Gata1low mutation increases the proliferation potential of a unique class of progenitor cells, similar in phenotype to adult common erythroid/megakaryocytic progenitors (MEPs), but with the "unique" capacity to generate erythroblasts, megakaryocytes, and mast cells in vitro. Conversely, progenitor cells phenotypically similar to mast cell progenitors (MCPs) are not detectable in the marrow from these mutants. At the single-cell level, about 11% of Gata1low progenitor cells, including MEPs, generate cells that will continue to proliferate in cultures for up to 4 months. In agreement with these results, trilineage (erythroid, megakaryocytic, and mastocytic) cell lines are consistently isolated from bone marrow and spleen cells of Gata1low mice. These results confirm the crucial role played by Gata1 in hematopoietic commitment and identify, as a new target for the Gata1 action, the restriction point at which common myeloid progenitors become either MEPs or MCPs.

Animals↗

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

Perturbation theory for the diffusion equation by use of the moments of the generalized temporal point-spread function. I. Theory.

We approach the perturbative solution to the diffusion equation for the case of absorbing inclusions embedded in a heterogeneous scattering medium by using general properties of the radiative transfer equation and the solution of the Fredholm equation of the second kind given by the Neumann series. The terms of the Neumann series are used to obtain the expression of the moments of the generalized temporal point-spread function derived in transport theory. The moments are calculated independently by using Monte Carlo simulations for validation of the theory. While the mixed moments are correctly derived from the theory by using the solution of the diffusion equation in the geometry of interest, in order to obtain the self moments we should reframe the problem in transport theory and use a suitable solution of the radiative transfer equation for the calculation of the multiple integrals of the corresponding Neumann series. Since the rigorous theory leads to impractical formulas, in order to simplify and speed up the calculation of the self moments, we propose a heuristic method based on the calculation of only a single integral and some scaling parameters. We also propose simple quadrature rules for the calculation of the mixed moments for speeding up the computation of perturbations due to multiple defects. The theory can be developed in the continuous-wave domain, the time domain, and the frequency domain. In a companion paper [J. Opt. Soc. Am. A23, 2119 (2006)] we discuss the conditions of applicability of the theory in practical cases found in diffuse optical imaging of biological tissues.

Algorithms↗

PubMed2006

Perturbation theory for the diffusion equation by use of the moments of the generalized temporal point-spread function. II. Continuous-wave results.

We investigate the performance of the method proposed in Part I of this paper in several situations of interest in diffuse optical imaging of biological tissues. Monte Carlo simulations were extensively used to validate the approximate scaling relationship between higher-order and first-order self moments of the generalized temporal point-spread function in semi-infinite and slab geometry. More specifically we found that in a wide range of cases the scaling parameters c1, c2, c3 [see Eq. (36) of Part I] lie in the intervals (1.48, 1.58), (3.1, 3.7), and (8.5, 11.5), respectively. The scaling relationships between higher-order and first-order self moments are useful for the calculation of the perturbation of a single defect in a straightforward way. Although these relationships are more accurate for inclusions of linear size less than approximately 6mm, their performance is also studied for larger inclusions. A good agreement, to within approximately 10%, was found between the perturbations of single and multiple defects calculated with the proposed method and those obtained by Monte Carlo simulations. We also provide formulas for the calculation of the moments up to the fourth order for which it is clear how lower-order moments can be used for the calculation of higher-order moments.

Algorithms↗

PubMed2005

Variegation of the phenotype induced by the Gata1low mutation in mice of different genetic backgrounds.

All mice harboring the X-linked Gata1low mutation in a predominantly CD1 background are born anemic and thrombocytopenic. They recover from anemia at 1 month of age but remain thrombocytopenic all their life and develop myelofibrosis, a syndrome similar to human idiopathic myelofibrosis, at 12 months. The effects of the genetic background on the myelofibrosis developed by Gata1low mice was assessed by introducing the mutation, by standard genetic approaches, in the C57BL/6 and DBA/2 backgrounds and by analyzing the phenotype of the different mutants at 12 to 13 (by histology) and 16 to 20 (by cytofluorimetry) months of age. Although all the Gata1low mice developed fibrosis at 12 to 13 months, variegations were observed in the severity of the phenotype expressed by mutants of different backgrounds. In C57BL/6 mice, the mutation was no longer inherited in a Mendelian fashion, and fibrosis was associated with massive osteosclerosis. Instead, DBA/2 mutants, although severely anemic, expressed limited fibrosis and osteosclerosis and did not present tear-drop poikilocytes in blood or extramedullary hemopoiesis in liver up to 20 months of age. We propose that the variegation in myelofibrosis expressed by Gata1low mutants of different strains might represent a model to study the variability of the clinical picture of the human disease.

Aging↗

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

Perturbation model for light propagation through diffusive layered media.

A fast and novel perturbation approach is proposed to account for the effects of absorbing inhomogeneities on light propagation through layered media. The calculation has been implemented with the Born approximation. Examples of results are reported both for a two- and for a three-layered medium. The method presented has been validated with the results of Monte Carlo simulations. The forward solver presented in this paper can be of significant use in investigating the feasibility of real experiments, e.g. for functional imaging studies.

Animals↗

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

Effect of the refractive index mismatch on light propagation through diffusive layered media.

The effect of the refractive index mismatch on light propagation through diffusive layers has been investigated. The refractive index mismatch changes the balance of energy inside the medium determining a temporal and spatial redistribution of light. Light penetration through the medium is obstructed (facilitated) by a negative (positive) refractive index step variation. An analytical solution of the time-dependent diffusion equation that accounts for this effect has been obtained. The solution has been validated by comparisons with the results of Monte Carlo simulations. An excellent description of light propagation is given even for a high refractive index mismatch.

Animals↗

PubMed2003

Procedure for retrieving the optical properties of a two-layered medium from time-resolved reflectance measurements.

A procedure for retrieving the optical properties of a two-layered diffusive medium based on an exact analytical solution of the diffusion equation and on relative multidistance time-resolved reflectance measurements is presented. The method overcomes some limitations of previously developed procedures. Five parameters of the medium have been fitted: the absorption and the reduced scattering coefficients of both layers and the thickness of the first layer. The actual values of the parameters are correctly retrieved by the procedure. The inversion procedure does not require an initial guess for the unknown optical properties, but the starting value for the thickness of the first layer needs to be estimated with an error smaller than 50%.

Journal Article↗

PubMed2003

Measurements of optical properties of high-density media.

Measurements of optical properties (scattering coefficient mu(s), absorption coefficient mu(a), reduced scattering coefficient mu(s)', and asymmetry factor g) have been carried out up to a volume particle concentration of rho = 0.227. The results for mu(s) and mu(s)' show significant deviations from the linear dependence on rho as expected when the independent scattering assumption is fulfilled. The asymmetry factor also changed significantly. In contrast, the dependence of mu(a) remained linear even at the largest concentration investigated. The simple linear dependence of absorption on the chromophore concentration expected from the independent scattering assumption is thus applicable also to spectroscopic measurements of dense media. A comparison with an approximate theoretical model based on the Foldy-Twersky equation is also reported. The model provides a good description of the dependence of mu(s) on particle concentration.

Computer Simulation↗

PubMed2003

Solution of the time-dependent diffusion equation for layered diffusive media by the eigenfunction method.

An exact solution of the time-dependent diffusion equation for the case of a two- and a three-layered finite diffusive medium is proposed. The method is based on the decomposition of the fluence rate in a series of eigenfunctions and upon the solution of the consequent transcendental equation for the eigenvalues obtained from the boundary conditions. Comparisons among the solution of the diffusion equation and the results of Monte Carlo simulations show the correctness of the proposed model.

Journal Article↗

PubMed2003

Assessment of an in situ temporal calibration method for time-resolved optical tomography.

A 32-channel time-resolved optical imaging device is developed at University College London to produce functional images of the neonatal brain and the female breast. Reconstruction of images using time-resolved measurements of transmitted light requires careful calibration of the temporal characteristics of the measurement system. Since they can often vary over a period of time, it is desirable to evaluate these characteristics immediately after, or prior to, the acquisition of image data. A calibration technique is investigated that is based on the measurement of light back-reflected from the surface of the object being imaged. This is facilitated by coupling each detector channel with an individual source fiber. A Monte Carlo model is employed to investigate the influence of the optical properties of the object on the back-reflected signal. The results of simulations indicate that their influence may be small enough to be ignored in some cases, or could be largely accounted for by a small adjustment to the calibrated data. The effectiveness of the method is briefly demonstrated by imaging a solid object with tissue-equivalent optical properties.

Brain↗

PubMed2002

Penetration depth of light re-emitted by a diffusive medium: theoretical and experimental investigation.

The depth at which photons penetrate into a diffusive medium before being re-emitted has been investigated with reference to a semi-infinite homogeneous medium illuminated by a pencil beam. By using the diffusion equation analytical expressions have been obtained for the probability that photons penetrate at a certain depth before being detected, and for the mean path length they travel inside each layer of the medium. Expressions have been obtained both for the cw and the time domain, and simple approximate scaling relationships describing the dependence on the scattering properties of the medium have been found. For time-resolved measurements both the probability and the mean path length are expected to be independent of the distance from the light beam at which the detector is placed and of the absorption coefficient of the medium. The penetration depth increases as the time of flight increases. In contrast, for cw measurements both the probability and the mean path length strongly depend on the distance and absorption. The penetration depth increases as the distance increases or absorption decreases. The accuracy of the analytical expressions has been demonstrated by comparisons with cw experimental results. The penetration depth and the mean path length provide useful information, for instance, for measurements of tissue oxygenation and for functional imaging of muscle and brain. In particular, the depth reached by received photons provides overall information on the volume of the tissue actually investigated, while the mean path is strictly related to the sensitivity to local variations of absorption.

Absorption↗

PubMed2002

Method to measure the optical properties of small volumes of diffusive media.

The method consists of measuring the perturbation provoked by a small volume of the diffusive medium on light propagating through a medium of known optical properties. The absorption and the reduced scattering coefficients of the medium are retrieved from multidistance continuous-wave measurements of transmittance. The inversion procedure is based on the solution of the diffusion equation obtained with a perturbative approach. The method has been validated with Monte Carlo results. Examples of experimental results are reported.

Diffusion↗

PubMed2002

Analytical approximate solutions of the time-domain diffusion equation in layered slabs.

Time-domain analytical solutions of the diffusion equation for photon migration through highly scattering two- and three-layered slabs have been obtained. The effect of the refractive-index mismatch with the external medium is taken into account, and approximate boundary conditions at the interface between the diffusive layers have been considered. A Monte Carlo code for photon migration through a layered slab has also been developed. Comparisons with the results of Monte Carlo simulations showed that the analytical solutions correctly describe the mean path length followed by photons inside each diffusive layer and the shape of the temporal profile of received photons, while discrepancies are observed for the continuous-wave reflectance or transmittance.

Diagnostic Imaging↗

PubMedDate not supplied

ARS Component B: structural characterization, tissue expression and regulation of the gene and protein (SLURP-1) associated with Mal de Meleda.

The ARS Component B gene (EMBL ID: HSARS81S, AC: X99977) encodes a 9 kD non-glycosylated polypeptide (also known as SLURP-1, SwissProt/TrEMBL: P55000), a soluble member of the human Ly6/uPAR superfamily. ARS Component B gene mutations have been implicated in Mal de Meleda. In this study we show by immunohistochemistry that SLURP-1 (secreted Ly-6/uPAR related protein, the protein product of the ARS Component B gene) is localized to human skin, exocervix, gums, stomach and esophagus. In the epidermis, keratinocytes underlying the stratum corneum are highly positive for SLURP1 immunostaining and cultured keratinocytes secrete the expected 9 kD protein. Circulating SLURP1 is detected in human plasma and urine. In the mouse, expression is evident in skin, eye, whole lung, trachea, esophagus and stomach. Human ARS Component B mRNA expression is regulated by retinoic acid, epidermal growth factor and interferon-gamma. The tissue localization and the association with Mal de Meleda suggest that ARS Component B and its protein product SLURP1 are implicated in maintaining the physiological and structural integrity of the keratinocyte layers of the skin.

Amino Acid Sequence↗