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Biomedical subjects

Sergio Fantini

Publications and source records attributed to Sergio Fantini.

At least 19 recordsLinked to original sources

Spatially weighted BOLD signal for comparison of functional magnetic resonance imaging and near-infrared imaging of the brain.

We introduce a weighted spatial average of the functional magnetic resonance imaging (fMRI) BOLD signal (blood oxygen level-dependent) that is appropriate for comparison with the changes in oxy- and deoxy-hemoglobin concentrations measured with near-infrared spectroscopy (NIRS) during brain activation. Because the BOLD signal shows a spatial dependence (both in shape and amplitude) within the region of activation, the location of the optical probe with respect to the region of BOLD activation should be taken into account for comparison of the BOLD and NIRS signals. Our new method is based on combining weighted contributions of the BOLD signal from each activated voxel, with a weight given by a hitting density function for photons migrating between a given pair of illumination and collection points. We present a case study where we have found that the new spatially weighted BOLD signal shows a high spatial and temporal correlation with the oxy- and deoxy-hemoglobin concentration changes measured with NIRS during a hand-tapping protocol. These findings reinforce the idea that fMRI and NIRS are sensitive to similar underlying hemodynamic changes, and indicate that the proposed weighted BOLD signal is needed for a quantitative comparison of BOLD and NIRS signals.

Brain↗

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↗

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↗

Three-element phased-array approach to diffuse optical imaging based on postprocessing of continuous-wave data.

We present a multielement phased-array approach to diffuse optical imaging based on postprocessing of continuous-wave data for the improvement of spatial resolution. In particular, we present a theoretical and experimental analysis of the performance of a three-element source array in the study of an optically turbid medium with two embedded cylindrical inclusions. We find that the proposed phased-array approach is able to resolve two cylinders with side-to-side separation of 10 mm that are not resolved by the intensity associated with a single light source.

Image Enhancement↗

Spatial and spectral information in optical mammography.

This article reviews our research activities in the area of optical mammography and relates them to the historical developments and the current state and trends in the field. The guiding threads for this article are the roles played in optical mammography by spatial and spectral information. The first feature, spatial information, is limited by the diffusive nature of light propagation but can take advantage of the exceptionally high optical contrast featured by blood vessels and blood-rich areas in the breast. We describe a method to correct for edge effects, a spatial second-derivative algorithm, and a two-dimensional phased-array approach that enhance the image contrast, the spatial resolution, and the depth discrimination in optical mammograms. The second feature, spectral information, is the most powerful and unique capability of optical mammography, and allows for functional measurements associated with hemoglobin concentration and oxygenation, water concentration, lipids content, and the wavelength dependence of tissue scattering. We present oxygenation-index images obtained from multi-wavelength optical data that point to the diagnostic potential of oxygenation information in optical mammography. The optimization of the spatial and spectral information in optical mammography has the potential to create a role for this imaging modality in the detection and monitoring of breast cancer.

Breast Neoplasms↗

Comment on the modified Beer-Lambert law for scattering media.

We present a concise overview of the modified Beer-Lambert law, which has been extensively used in the literature of near-infrared spectroscopy (NIRS) of scattering media. In particular, we discuss one form of the modified Beer-Lambert law that is commonly found in the literature and that is not strictly correct. However, this incorrect form of the modified Beer-Lambert law still leads to the correct expression for the changes in the continuous wave optical signal associated with changes in the absorption coefficient of the investigated medium. Here we propose a notation for the modified Beer-Lambert law that keeps the typical form commonly found in the literature without introducing any incorrect assumptions.

Biophysics↗

Optical measurements of absorption changes in two-layered diffusive media.

We have used Monte Carlo simulations for a two-layered diffusive medium to investigate the effect of a superficial layer on the measurement of absorption variations from optical diffuse reflectance data processed by using: (a) a multidistance, frequency-domain method based on diffusion theory for a semi-infinite homogeneous medium; (b) a differential-pathlength-factor method based on a modified Lambert-Beer law for a homogeneous medium and (c) a two-distance, partial-pathlength method based on a modified Lambert-Beer law for a two-layered medium. Methods (a) and (b) lead to a single value for the absorption variation, whereas method (c) yields absorption variations for each layer. In the simulations, the optical coefficients of the medium were representative of those of biological tissue in the near-infrared. The thickness of the first layer was in the range 0.3-1.4 cm, and the source-detector distances were in the range 1-5 cm, which is typical of near-infrared diffuse reflectance measurements in tissue. The simulations have shown that (1) method (a) is mostly sensitive to absorption changes in the underlying layer, provided that the thickness of the superficial layer is approximately 0.6 cm or less; (2) method (b) is significantly affected by absorption changes in the superficial layer and (3) method (c) yields the absorption changes for both layers with a relatively good accuracy of approximately 4% for the superficial layer and approximately 10% for the underlying layer (provided that the absorption changes are less than 20-30% of the baseline value). We have applied all three methods of data analysis to near-infrared data collected on the forehead of a human subject during electroconvulsive therapy. Our results suggest that the multidistance method (a) and the two-distance partial-pathlength method (c) may better decouple the contributions to the optical signals that originate in deeper tissue (brain) from those that originate in more superficial tissue layers.

Absorption↗

Bilateral near-infrared monitoring of the cerebral concentration and oxygen-saturation of hemoglobin during right unilateral electro-convulsive therapy.

Reductions in right prefrontal cerebral blood flow have been correlated with symptomatic improvement in depressed individuals receiving electroconvulsive therapy (ECT). Non-invasive near infrared spectroscopy has previously been shown to reliably measure changes in cerebral hemoglobin concentrations and oxygen saturation. In this study, we measured the concentration and oxygen saturation of hemoglobin on the right and left frontal brain regions of nine patients during right unilateral ECT. In all patients, we have found that the electrically induced seizure causes a stronger cerebral deoxygenation on the side ipsilateral to the electrical current (-21+/-5%) with respect to the contralateral side (-6+/-4%). On the brain side ipsilateral to the ECT electrical discharge, we have consistently observed a discharge-induced decrease in the total hemoglobin concentration, i.e. in the cerebral blood volume, by -7+/-3 microM, as opposed to an average increase by 6+/-3 microM on the contralateral side. The ipsilateral decrease in blood volume is assigned to a vascular constriction associated with the electrical discharge, as indicated by the observed decrease in cerebral oxy-hemoglobin concentration and minimal change in deoxy-hemoglobin concentration during the electrical discharge on the side of the discharge. These findings provide indications about the cerebral hemodynamic/metabolic mechanisms associated with ECT, and may lead to useful parameters to predict the individual clinical outcome of ECT.

Adult↗

Characterization of spatial and temporal variations in the optical properties of tissuelike media with diffuse reflectance imaging.

We describe a method to characterize spatial or temporal changes in the optical properties of turbid media using diffuse reflectance images acquired under broad-beam illumination conditions. We performed experiments on liquid phantoms whose absorption (mu(a)) and reduced scattering (mu(s)') coefficients were representative of those of biological tissues in the near infrared. We found that the relative diffuse reflectance R depends on mu(a) and mu(s)' only through the ratio mu(a)/mu(s)' and that dependence can be well described with an analytical expression previously reported in the literature [S. L. Jacques, Kluwer Academic Dordrecht (1996)]. We have found that this expression for R deviates from experimental values by no more than 8% for various illumination and detection angles within the range 0 degrees-30 degrees. Therefore, this analytical expression for R holds with good approximation even if the investigated medium presents curved or irregular surfaces. Using this expression, it is possible to translate spatial or temporal changes in the relative diffuse reflectance from a turbid medium into quantitative estimates of the corresponding changes of (mu(a)/mu(s)')(1/2). In the case of media with optical properties similar to those of tissue in the near infrared, we found that the changes mu(a)/mu(s)' should occur over a volume approximately 2 mm deep and 4 mm x 4 mm wide to apply this expression.

Models, Theoretical↗

Absolute frequency-domain pulse oximetry of the brain: methodology and measurements.

A new method to non-invasively measure the absolute tissue oxygen saturation (SO2) and arterial oxygen saturation (fdSaO2) by frequency-domain spectroscopy is described. This method is based on the quantitative measurement of the tissue absorption spectrum, which is used to determine global SO2. From the amplitude of absorption changes caused by arterial pulsation oscillations, in the range of 633-841 nm, the fdSaO2 can be calculated. During deoxygenation (air/N2 mixture) experiments, we measured the fdSaO2 and SO2 on the forehead of three healthy volunteers and compared them to the arterial oxygen saturation measured by conventional pulse oximetry (poSaO2) on the finger. fdSaO2 and poSaO2 agree very well (mean difference: -1.2 +/- 2.6%). Changes in SO2 were systematically smaller than in fdSaO2 or poSaO2 probably due to autoregulation. The measurements with 4 and 8 wavelengths had comparable quality.

Brain↗

Hemodynamic evoked response of the sensorimotor cortex measured noninvasively with near-infrared optical imaging.

We have performed a noninvasive bilateral optical imaging study of the hemodynamic evoked response to unilateral finger opposition task, finger tactile, and electrical median nerve stimulation in the human sensorimotor cortex. This optical study shows the hemoglobin-evoked response to voluntary and nonvoluntary stimuli. We performed measurements on 10 healthy volunteers using block paradigms for motor, sensory, and electrical stimulations of the right and left hands separately. We analyzed the spatial/temporal features and the amplitude of the optical signal induced by cerebral activation during these three paradigms. We consistently found an increase (decrease) in the cerebral concentration of oxy-hemoglobin (deoxy-hemoglobin) at the cortical side contralateral to the stimulated side. We observed an optical response to activation that was larger in size and amplitude during voluntary motor task compared to the other two stimulations. The ipsilateral response was consistently smaller than the contralateral response, and even reversed (i.e., a decrease in oxy-hemoglobin, and an increase in deoxy-hemoglobin) in the case of the electrical stimulation. We observed a systemic contribution to the optical signal from the increase in the heart rate increase during stimulation, and we made a first attempt to subtract it from the evoked hemoglobin signal. Our findings based on optical imaging are in agreement with results in the literature obtained with positron emission tomography and functional magnetic resonance imaging.

Adult↗

Spatial second-derivative image processing: an application to optical mammography to enhance the detection of breast tumors.

We present an image-processing method that enhances the detection of regions of higher absorbance in optical mammograms. At the heart of this method lies a second-derivative operator that is commonly employed in edge-detection algorithms. The resulting images possess a high contrast, an automatic display scale, and a greater sensitivity to smaller departures from the local background absorbance. Moreover, the images are free of artifacts near the breast edge. This second-derivative method enhances the display of structural information in optical mammograms and may be used to robustly select areas of interest to be further analyzed spectrally to determine the oxygenation level of breast lesions.

Aged↗

A haemodynamic model for the physiological interpretation of in vivo measurements of the concentration and oxygen saturation of haemoglobin.

We present a model that describes the effect of physiological parameters such as the speed of blood flow, local oxygen consumption, capillary recruitment, and vascular dilation/constriction on the concentration and oxygen saturation of haemoglobin in tissue. This model can be used to guide the physiological interpretation of haemodynamic and oximetric data collected in vivo with techniques such as optical imaging, near-infrared spectroscopy and functional magnetic resonance imaging. In addition to providing a formal description of well-established results (exercise-induced hyperemia, reperfusion hyperoxia, decrease in the concentration of deoxyhaemoglobin induced by brain activity, measurement of arterial saturation by pulse oximetry, etc.), this model suggests that the superposition of asynchronous contributions from the arterial, capillary and venous haemoglobin compartments may be at the origin of observed out-of-phase oscillations of the oxyhaemoglobin and deoxyhaemoglobin concentrations in tissue.

Hemodynamics↗

Quantitative oximetry of breast tumors: a near-infrared method that identifies two optimal wavelengths for each tumor.

We present a noninvasive optical method to measure the oxygen saturation of hemoglobin in breast lesions. This method introduces the novel concept that the best choice of near-infrared wavelengths for noninvasive tumor oximetry consists of a wavelength pair (lambda1, lambda2) within the range 680-880 nm, where the specific values of lambda1 and lambda2 depend on the optical properties of the specific tumor under examination. Our method involves two steps: (1) identify the optimal wavelength pair for each tumor and (2) measure the tumor oxygenation using the optical data at the two selected wavelengths. We have tested our method by acquiring experimental optical data from turbid media containing cylindrical or irregularly shaped inhomogeneities and by computing theoretical data for the case of spherical lesions embedded in a highly scattering medium. We have found that our optical method can provide accurate and quantitative measurements of the oxygenation of embedded lesions without requiring knowledge of their size, shape, and depth.

Breast Neoplasms↗

Near-infrared spiroximetry: noninvasive measurements of venous saturation in piglets and human subjects.

We present a noninvasive method to measure the venous oxygen saturation (Sv(O(2))) in tissues using near-infrared spectroscopy (NIRS). This method is based on the respiration-induced oscillations of the near-infrared absorption in tissues, and we call it spiroximetry (the prefix spiro means respiration). We have tested this method in three piglets (hind leg) and in eight human subjects (vastus medialis and vastus lateralis muscles). In the piglet study, we compared our NIRS measurements of the Sv(O(2)) (Sv(O(2))-NIRS(resp)) with the Sv(O(2)) of blood samples. Sv(O(2))-NIRS(resp) and Sv(O(2)) of blood samples agreed well over the whole range of Sv(O(2)) considered (20-95%). The two measurements showed an average difference of 1.0% and a standard deviation of the difference of 5.8%. In the human study, we found a good agreement between Sv(O(2))-NIRS(resp) and the Sv(O(2)) values measured with the NIRS venous occlusion method. Finally, in a preliminary test involving muscle exercise, Sv(O(2))-NIRS(resp) showed an expected postexercise decrease from the initial baseline value and a subsequent recovery to baseline.

Adult↗

Spatial distribution of vastus lateralis blood flow and oxyhemoglobin saturation measured at the end of isometric quadriceps contraction by multichannel near-infrared spectroscopy.

Muscle blood flow (MBF) and muscle oxygen saturation (SmO(2)) were measured at eight locations (four proximal, four distal) over a 4 x 8 cm(2) area of the vastus lateralis at rest and immediately after isometric, maximal quadriceps contraction using multichannel, frequency-domain, near-infrared spectroscopy. A venous occlusion was applied 20 s before the end of the exercise, so that the venous-occlusion-induced increase in total hemoglobin was recorded without any delay after the end of the exercise. Therefore, we were able to investigate the relationship between the exercise-induced changes in vastus lateralis MBF and SmO(2). After exercise, MBF increased significantly at each measured location. Comparing the MBF values measured at the end of exercise in the proximal and distal regions, we observed that only one proximal region had a significantly higher MBF than the corresponding distal one. The maximum desaturation measured during exercise was positively correlated with the postexercise to pre-exercise MBF ratio in both the proximal (P=0.016) and distal (P=0.0065) regions. These data confirm that frequency-domain tissue oximeters are noninvasive, powerful tools to investigate the spatial and temporal features of muscle blood flow and oxygenation, with potential applications in areas of pathophysiology.

Adult↗

Near-infrared imaging of the human breast: complementing hemoglobin concentration maps with oxygenation images.

We have previously reported a comparison between edge-corrected near-infrared optical mammograms and those that have undergone a further image-processing step based on a spatial second derivative. In this work, we go a step further by combining the second-derivative images from four wavelengths (690, 750, 788, and 856 nm) to obtain oxygenation-index images. While the spatial second derivative improves contrast and allows for visibility of fine structures in the images, thereby improving the sensitivity to tumor detection, additional information is needed to avoid false-positive results. The oxygenation-index images are introduced to address this issue. Oxygenation information may help discriminate benign from malignant breast lesions, thereby effectively complementing single-wavelength optical mammograms that display optically dense regions within the breast with high sensitivity.

Aged↗

Two-dimensional phased arrays of sources and detectors for depth discrimination in diffuse optical imaging.

We present a multisource, multidetector phased-array approach to diffuse optical imaging that is based on postprocessing continuous-wave data. We previously showed that this approach enhances the spatial resolution of diffuse optical imaging. We now demonstrate the depth discrimination capabilities of this approach and its potential to perform tomographic sectioning of turbid media. The depth discrimination results from the dependence of the sensitivity function on the depth coordinate z. To demonstrate the potential of this approach, we perform an experimental study of a turbid medium containing cylindrical inhomogeneities that are placed 2.0, 3.0, and 4.0 cm from a seven-element, 2-D source array. A single detector element is placed at a distance of 6.0 cm from the source array, and the measurement is repeated after switching the positions of the detector and the source array to simulate the case where both sources and detectors consist of a 2-D array of elements. We find that the proposed phased-array method is able to separate cylinders at different depths, thus showing cross-sectioning capabilities.

Equipment Design↗