Antonio Pifferi
Politecnico di Milano, Dipartimento di fisica, Faculty Member
The glutathione (GSH)-glutathione S-transferase (GST) detoxification system is an important element in cellular defence against injurious agents and anticancer drugs. GST isoenzymes may represent biochemical markers of neoplastic... more
The glutathione (GSH)-glutathione S-transferase (GST) detoxification system is an important element in cellular defence against injurious agents and anticancer drugs. GST isoenzymes may represent biochemical markers of neoplastic transformation, and, possibly, drug resistance is associated with altered GST-isoenzyme levels. The ability to measure GST-isoenzymes in cell populations would be useful for several biological and clinical applications. We have developed an immunofluorescence flow cytometric method for the simultaneous detection of different GST-isoenzymes and of DNA in fixed cells. Due to the impossibility of working under saturating conditions for the anti-GST antibody, a normalizing procedure was developed to permit quantitative analysis of single cells labelled with the anti-GST antibody at high dilution. A theoretical model and experimental data supported the use of this procedure. The method proposed is general and could be applied to other antibodies in order to obtain quantitative data outside saturating conditions. The method was challenged in different applications in order to compare it with other classical techniques. First, we characterized sublines resistant to different anticancer drugs with respect to variations of GST isotypes. In a second application, we studied the intercellular heterogeneity of GST content in mouse renal cells. In addition, GST was determined in aneuploid cells from solid tumor biopsies by separation from diploid cells on the basis of DNA content. Finally, GST distribution during cell-cycle progression was studied in two different cell lines by the biparametric analysis of GST/DNA.
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Research Interests: Cancer, Flow Cytometry, Cell Cycle, DNA, Cell line, and 3 moreHumans, Female, and Nucleic Acid Conformation
Intracellular glutathione (GSH) content was measured by flow cytometry using monochlorobimane (mBCl) and by the enzymatic assay in a set of 6 sublines of murine L1210 leukemia cells made resistant to DNA-interacting agents having distinct... more
Intracellular glutathione (GSH) content was measured by flow cytometry using monochlorobimane (mBCl) and by the enzymatic assay in a set of 6 sublines of murine L1210 leukemia cells made resistant to DNA-interacting agents having distinct mechanisms of action: L-phenylalanine mustard (L-PAM), 1,3-bis(2-chloroethyl)-I-nitrosourea (BCNU), cisplatin (DDP), N-deformyl-N-(4-N,N-bis(2-chloroethylamino) benzoyl) distamycin A (FCE 24517), doxorubicin (DX) and 3'-deamino-3' (2-methoxy-4-morpholinyl)-doxorubicin (FCE 23762). A significant correlation was demonstrated between the mean intracellular mBCl fluorescence values measured by flow cytometry and levels of GSH measured by the classical enzymatic assay, despite the possible influence of glutathione-S-transferases and of other thiols on the mBCl fluorescence. Although less specific, the flow cytometric method is more informative than the enzymatic assay, allowing detection of fluorescence distributions, which we proved to be characteristic of each subline. In order to assess a procedure enabling a quantitative analysis to be made of intercellular GSH heterogeneity, we propose the use of appropriate thresholds and parameters of the mBCl flow cytometric distribution. By use of this analysis procedure, distinct types of alterations, with respect to the heterogeneity distribution of the parental L1210 cell line, have been evidenced in resistant cells. A uniform increase in mBCl fluorescence was observed among cells of the sublines resistant to L-PAM and FCE-24517. The mean mBCl fluorescence increase in sublines resistant to DX and DDP was due to a higher number of cells with fairly high mBCl fluorescence, but still within the range spanned by the parental cell line. A less heterogeneous mBCl fluorescence distribution was found in the L1210 subline resistant to FCE 23762, which was, however, similar to a cloned sensitive line. Though GSH was linked to the principal cause of drug resistance only in the L-PAM-resistant cell line, alterations in heterogeneity, as detected by mBCl fluorescence distributions, were found in 5 out of 6 resistant lines.
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Twenty-three human xenografts, including five colon, five gastric, nine lung (three small cell lung cancer) and four breast carcinomas, were investigated for their sensitivity to nitrosoureas, dacarbazine (DTIC), cyclophosphamide (CTX)... more
Twenty-three human xenografts, including five colon, five gastric, nine lung (three small cell lung cancer) and four breast carcinomas, were investigated for their sensitivity to nitrosoureas, dacarbazine (DTIC), cyclophosphamide (CTX) and cisplatin (DDP). In 12 cases, at least one of the drugs produced complete or partial remission, in 2, a minor regression was observed and in the other 9, treatment was ineffective. The level of sensitivity to each drug, using a score from 1 to 5, was correlated to three biochemical parameters reported to be involved in resistance to alkylating agents: glutathione (GSH), glutathione transferase (GST) and O6-alkylguanine-DNA-alkyltransferase (AGT). A wide variability was found in these parameters in the xenografts investigated. No correlation was found between any of the three parameters and sensitivity to the drugs used or between sensitivity to one drug and to any of the other drugs tested. These results illustrate the complexity of the question of resistance to alkylating agents and indicate that, at least in xenografts, the biochemical parameters examined are not predictive of response to alkylating agents.
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ABSTRACT We developed a dual-wavelength multichannel system for time-resolved reflectance measurements based on the time-correlated single-photon counting (TCSPC) technique. The output pulses of two laser diodes (672 and 818 nm, 80 MHz... more
ABSTRACT We developed a dual-wavelength multichannel system for time-resolved reflectance measurements based on the time-correlated single-photon counting (TCSPC) technique. The output pulses of two laser diodes (672 and 818 nm, 80 MHz pulse repetition rate, 1 mW average power, 100 ps FWHM) are delayed and coupled into a multimode graded-index fiber (50/125 mu m) and injected into the tissue. The reflectance photons are collected by 1 me fibers and detected by a multianode photomultiplier, The output signals of the photomultiplier are redirected by a router to different memory blocks of a TCSPC PC board, allowing the parallel acquisition of the curves. The solution of the time-dependent diffusion equation for the reflectance through a semi infinite homogeneous medium is best-fitted to the experimental curves, leading to the simultaneous estimate of the reduced scattering and absorption coefficients at two wavelengths in four different positions. The minimum acquisition time is 100 ms, fixed by the maximum count rate of the TCSPC PC board (1 MHz) and by the required S/N ratio. The performances of the system were tested on phantoms in terms of stability and accuracy in the determination of absolute values of the absorption and reduced scattering coefficients. Preliminary in vivo measurements were performed on healthy volunteers to estimate absorption and reduced scattering in different physiological conditions and to derive tissue functional parameters such as tissue oxygenation.
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ABSTRACT Concentrations of oxygenated and deoxygenated hemoglobin, lipids and water in female breast are presented for 113 breasts, as a result of a clinical study on optical mammography. They correlate well with demographic parameters of... more
ABSTRACT Concentrations of oxygenated and deoxygenated hemoglobin, lipids and water in female breast are presented for 113 breasts, as a result of a clinical study on optical mammography. They correlate well with demographic parameters of subjects.
The spatial dependence of the optical properties of the female breast was investigated in the wavelength range 600–1000nm using a fully automated system for time-resolved reflectance spectroscopy. Both absorption and reduced scattering... more
The spatial dependence of the optical properties of the female breast was investigated in the wavelength range 600–1000nm using a fully automated system for time-resolved reflectance spectroscopy. Both absorption and reduced scattering spectra of the breast of two healthy volunteers, having different ages (24 and 44 years), were measured at eight different angular positions (0°, 45°, 90°, 135°, 180°, 225°,
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ABSTRACT In vivo absorption and scattering spectra of different human tissues were obtained using a system for time-resolved reflectance measurements in the wavelength range from 610 nm to 1010 nm, every 5 nm. The system is based on a dye... more
ABSTRACT In vivo absorption and scattering spectra of different human tissues were obtained using a system for time-resolved reflectance measurements in the wavelength range from 610 nm to 1010 nm, every 5 nm. The system is based on a dye laser and a Ti:Sapphire laser as light sources and an electronic chain for time-correlated single-photon counting for detection. Measurements were performed on the breast, the arm, the abdomen, and the forehead of healthy volunteers. The scattering spectra decrease upon increasing the wavelength, while the absorption spectra show the spectral features of oxy- and deoxyhemoglobin, water, and lipids.
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We developed a time-resolved scanning system for fluorescence molecular imaging in diffusive media, such as biological tissues. In the present work the system is described and characterized in terms of linearity against optical parameters... more
We developed a time-resolved scanning system for fluorescence molecular imaging in diffusive media, such as biological tissues. In the present work the system is described and characterized in terms of linearity against optical parameters of the sample and against homogeneously diffuse fluorescent dye. Finally, preliminary measurements performed on phantom are presented, pointing out the ability of our system to produce
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Rinaldo Cubeddu, Antonio Pifferi, Paola Taroni, and Gianluca Valentini CEQSE-CNR and INFM-Dipartimento di Fisica, Politecnico di Milano, Piazza Leonardo da Vinci 32, 20133 Milano, Italy ... Gianfranco Canti Department of Pharmacology,... more
Rinaldo Cubeddu, Antonio Pifferi, Paola Taroni, and Gianluca Valentini CEQSE-CNR and INFM-Dipartimento di Fisica, Politecnico di Milano, Piazza Leonardo da Vinci 32, 20133 Milano, Italy ... Gianfranco Canti Department of Pharmacology, Universita di Milano, Via ...
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ABSTRACT We developed a dual-wavelength multichannel system for near infrared tissue oximetry based on the time-correlated single-photon counting (TSCPC) technique. The light sources are two pulsed laser diodes (672 nm and 818 nm, 1 mW... more
ABSTRACT We developed a dual-wavelength multichannel system for near infrared tissue oximetry based on the time-correlated single-photon counting (TSCPC) technique. The light sources are two pulsed laser diodes (672 nm and 818 nm, 1 mW average power, 100 ps pulse duration, 80 MHz repetition rate). The time-resolved reflectance photons are detected by a multi- anode photomultiplier and the output signals are redirected by a router to different memory blocks of a TCSPC PC board (25 ps temporal resolution, 1 MHz acquisition frequency). The system accuracy in determining the absorption and reduced scattering coefficients were tested on phantoms. Preliminary in vivo tissue oxygenation measurements were performed on healthy volunteers in different physiological conditions.
» View Full Text: Acrobat PDF (70 KB) * * Note that full-text PDFs from conferences typically contain 1-3 pages of content, some or all of which might be an abstract, summary, or miscellaneous items. ... The absorption spectrum of... more
» View Full Text: Acrobat PDF (70 KB) * * Note that full-text PDFs from conferences typically contain 1-3 pages of content, some or all of which might be an abstract, summary, or miscellaneous items. ... The absorption spectrum of collagen (630-1000 nm) was measured and used - ...
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The spatial dependence of the optical properties of the female breast was investigated in the wavelength range 600–1000nm using a fully automated system for time-resolved reflectance spectroscopy. Both absorption and reduced scattering... more
The spatial dependence of the optical properties of the female breast was investigated in the wavelength range 600–1000nm using a fully automated system for time-resolved reflectance spectroscopy. Both absorption and reduced scattering spectra of the breast of two healthy volunteers, having different ages (24 and 44 years), were measured at eight different angular positions (0°, 45°, 90°, 135°, 180°, 225°,
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In this work we present a novel diffuse fluorescence imaging system, based on time-resolved two-wavelength double reflectance and transmittance setup for slab geometry samples. We describe the hardware setup, showing its compactness and... more
In this work we present a novel diffuse fluorescence imaging system, based on time-resolved two-wavelength double reflectance and transmittance setup for slab geometry samples. We describe the hardware setup, showing its compactness and versatility and show the results on preliminary measurements on phantoms. We fully assessed the performances and the dynamic ranges of the system. We validated its ability of recovering the optical properties of the bulk medium, for samples with scattering and absorption coefficients similar to those of biological tissues and with thicknesses of about 2 cm. Moreover we assess the linearity of the recorded signals against the fluorophore concentration, when it is homogeneously diffused in the phantom or concentrated inside a sealed inclusion. In both cases we observe again a fairly good linearity, over three orders of magnitude, from 10(-8)M to 10(-5)M. With the fluorescent inclusion we were also able to assess the imaging capabilities of the system, in terms of spatial resolution, which we appraise in about 3 mm, and in terms of imaging sensitivity (the smallest quantity of fluorescent dye distinguishable from the homogeneous background), settled to 200 fmol. Since the recorded data are time resolved, we could also estimate the dye fluorescence lifetime and build early and late time gate images. We finally discuss some of the criticalities of the proposed system and the developments we are currently carrying on in order to adapt it for in vivo measurements.
Research Interests: Engineering, Fluorescence Microscopy, Confocal Microscopy, Tomography, Fluorescence Lifetime, and 13 moreScientific Instruments, Scientific, Diffusion, Physical sciences, Fluorescence Imaging, Optical Properties, CHEMICAL SCIENCES, Image Enhancement, Reproducibility of Results, Sensitivity and Specificity, Equipment Design, Equipment Failure Analysis, and Nephelometry and Turbidimetry
A solid tissue phantom made of agar, Intralipid and black ink is described and characterized. The preparation procedure is fast and easily implemented with standard laboratory equipment. An instrumentation for time-resolved transmittance... more
A solid tissue phantom made of agar, Intralipid and black ink is described and characterized. The preparation procedure is fast and easily implemented with standard laboratory equipment. An instrumentation for time-resolved transmittance measurements was used to determine the optical properties of the phantom. The absorption and the reduced scattering coefficients are linear with the ink and Intralipid concentrations, respectively. A systematic decrease of the reduced scattering coefficient dependent on the agar content is observed, but can easily be managed. The phantom is highly homogeneous and shows good repeatability among different preparations. Moreover, agar inclusions can be easily embedded in either solid or liquid matrixes, and no artefacts are caused by the solid-solid or solid-liquid interfaces. This allows one to produce reliable and realistic inhomogeneous phantoms with known optical properties, particularly interesting for studies on optical imaging through turbid media.
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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... more
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.
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Time-resolved reflectance was used to measure the absorption spectrum of hematoporphyrin derivative (HpD) in vivo in a murine tumor model. Reflectance measurements were performed in the 600-640 nm range on mice bearing the L1210 leukemia.... more
Time-resolved reflectance was used to measure the absorption spectrum of hematoporphyrin derivative (HpD) in vivo in a murine tumor model. Reflectance measurements were performed in the 600-640 nm range on mice bearing the L1210 leukemia. Then the animals were administered 25 mg/kg body weight of HpD intraperitoneally. One hour later the reflectance measurements were repeated. Fitting of the data using the diffusion theory allowed assessment of the absorption coefficient before and after the administration. As a difference between the latter and the former data, the in vivo absorption spectrum of HpD was evaluated. Maximum absorption was measured at 620-625 nm. Similar spectral behavior was obtained for HpD in solution in the presence of low-density lipoproteins.
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Tumor detection has been carried out in mice sensitized with hematoporphyrin derivative (HpD) by measuring the spatial distribution of the fluorescence lifetime of the exogenous compound. This result has been achieved using a time-gated... more
Tumor detection has been carried out in mice sensitized with hematoporphyrin derivative (HpD) by measuring the spatial distribution of the fluorescence lifetime of the exogenous compound. This result has been achieved using a time-gated video camera and a suitable mathematical processing that led to the so-called "lifetime images." Extensive experimental tests have been performed on mice bearing the MS-2 fibrosarcoma or the L1210 leukemia. Lifetime images of mice show that the fluorescence decay of HpD is appreciably slower in the tumor than in healthy tissues nearby, allowing a reliable detection of the neoplasia. The lengthening of the lifetime in tumors depends little on the drug dose, which in our experiments could be lowered down to 0.1 mg/kg body weight, still allowing a definite tumor detection. In order to ascertain the results achieved with the imaging apparatus, high-resolution spectroscopy, based on a time-correlated single photon counting system, has also been performed to measure the fluorescence lifetime of the drug inside the tumor and outside. The outcomes obtained with two techniques are in good agreement.
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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... more
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.
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Four different expressions, derived from the diffusion theory or the random walk model, were used to fit time-resolved reflectance data for the evaluation of tissue optical properties. The experimental reflectance curves were obtained... more
Four different expressions, derived from the diffusion theory or the random walk model, were used to fit time-resolved reflectance data for the evaluation of tissue optical properties. The experimental reflectance curves were obtained from phantoms of known optical parameters (absorption and transport scattering coefficients) covering the range of typical values for biological tissues between 600 and 900 nm. The measurements were performed using an instrumentation for time-correlated single-photon counting. The potential of the four methods in the assessment of the absorption and transport scattering coefficients was evaluated in terms of absolute error, linearity error, and dispersion of data. Each method showed different performances depending on the optical properties of the sample and the experimental conditions. We propose some criteria for the optimal choice of the fitting method to be used in different applications.
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ABSTRACT A realistic tissue phantom was used to study the spatial resolution of time-resolved transmittance imaging techniques based on time gating and on the plot of the optical coefficients obtained from the fit to a theoretical model.... more
ABSTRACT A realistic tissue phantom was used to study the spatial resolution of time-resolved transmittance imaging techniques based on time gating and on the plot of the optical coefficients obtained from the fit to a theoretical model. Time-resolved transmittance curves were collected along a line across a sharp transition between two regions of different, but realistic, optical properties. The effect of scattering and absorption edges were examined to get a deeper insight into the problem of imaging both scattering and absorption inhomogeneities. For both the fitted optical parameters and the integrated intensity, the edge spread function was evaluated and fitted to an error function, providing quantitative information on both spatial resolution and edge location. The plot of the fitted scattering coefficient and the intensity integrated within an early gate have similar resolution, while the performance of the fitted absorption coefficient is definitely worse. The edge location is more sensitive to the optical contrast with the fitted scattering than with the integrated intensity. © 1999 American Association of Physicists in Medicine.
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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.... more
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). .
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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... more
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.
Research Interests: Biomedical Engineering, Water, Optical coherence tomography, Biomedical, Lipids, and 15 moreBiomedical Optics, Humans, Female, Time Resolved, Breast, Lipid metabolism, Optical Properties, Mammography, Optical physics, Middle Aged, Optometry and Ophthalmology, Oxygen, Reproducibility of Results, Sensitivity and Specificity, and Hemoglobins
... The holder is made of black-anodized aluminum to avoid any undesired and uncontrollable reflections. ... from the fiber end to the PMT are placed in a black-anodized light ... B. Time-ResohedMeasurements The accuracy of a... more
... The holder is made of black-anodized aluminum to avoid any undesired and uncontrollable reflections. ... from the fiber end to the PMT are placed in a black-anodized light ... B. Time-ResohedMeasurements The accuracy of a time-resolved reflectance measurement of pa or p: on a ...
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Research Interests: Biomedical Engineering, Light Scattering, Principal Component Analysis, Biosystems engineering, Discriminant Analysis, and 9 moreModel Selection, Statistical Techniques in Spatial Analysis, Tomato, Reflectance Spectroscopy, Biosystems, Linear Regression, Fruit Quality, Total Soluble Solids, and Time Domain
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An effective projection imaging technique is proposed that allows the detection of realistic optical inhomogeneities in highly diffusive media and the discrimination between scattering and absorption contributions. The method is based on... more
An effective projection imaging technique is proposed that allows the detection of realistic optical inhomogeneities in highly diffusive media and the discrimination between scattering and absorption contributions. The method is based on information derived from time-resolved transmittance measurements. Scattering inhomogeneities are discriminated using maps of the transport scattering coefficient, as provided by best fitting of the diffusion theory to experimental data. Absorption variations are effectively classified by time-gating on the tail of the transmittance pulse. Images were constructed from matrices of time-resolved transmittance measurements performed with a mode-locked dye laser and an electronic chain for time-correlated single photon counting. Data were collected from realistic tissue phantoms containing cylindrical inhomogeneities (1-cm height and 1-cm diameter) embedded in a 5 cm thick turbid slab. The optical coefficients of the inclusions were varied separately ((mu) s' equals 5 divided by 20 cm-1 and (mu) a equals 0.025 divided by 0.4 cm-1) with respect to the background values ((mu) s ' equals 10 cm-1 and (mu) a equals 0.1 cm-1). The overall acquisition time was less than 15 min. In all the experimental conditions considered, the method discriminated efficiently the scattering from the absorption contribution when either of the coefficients or both of them were inhomogeneous.
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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... more
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.
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We developed a compact dual-wavelength multichannel tissue oximeter based on the time-correlated single-photon counting (TCSPC) technique. The light sources are two pulsed diode lasers (output wavelengths of 672 and 818 nm, an average... more
We developed a compact dual-wavelength multichannel tissue oximeter based on the time-correlated single-photon counting (TCSPC) technique. The light sources are two pulsed diode lasers (output wavelengths of 672 and 818 nm, an average power of 1 mW, a pulse duration of 100 ps, ...
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ABSTRACT Not Available