Lorenzo Spinelli

Time domain functional NIRS imaging for human brain mapping

This review is aimed at presenting the state-of-the-art of time domain (TD) functional near-infrared spectroscopy (fNIRS). We first introduce the physical principles, the basics of modeling and data analysis. Basic instrumentation components (light sources, detection techniques, and delivery and collection systems) of a TD fNIRS system are described. A survey of past, existing and next generation TD fNIRS systems used for research and clinical studies is presented. Performance assessment of TD fNIRS systems and standardization issues are also discussed. Main strengths and weakness of TD fNIRS are highlighted, also in comparison with continuous wave (CW) fNIRS. Issues like quantification of the hemodynamic response, penetration depth, depth selectivity, spatial resolution and contrast-to-noise ratio are critically examined, with the help of experimental results performed on phantoms or in vivo. Finally we give an account on the technological developments that would pave the way for a broader use of TD fNIRS in the neuroimaging community.

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.

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). .

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.

Multi-channel time-resolved system for functional near infrared spectroscopy

We have designed a compact dual wavelength multi-channel time-resolved system for functional near infrared spectroscopy. The system enables 16 sources and up to 64 collection points, with a minimum acquisition time of 5 ms per channel. Performances of the system have been tested on tissue phantoms in terms of linearity, noise, stability and reproducibility. Preliminary measurements on volunteers have been performed to validate the instrument capability to acquire in vivo maps of the hemodynamic parameters in the muscle during arterial occlusion and in the adult head during a finger tapping experiment.

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.

Seven-wavelength time-resolved optical mammography extending beyond 1000 nm for breast collagen quantification

Our multi-wavelength time-resolved optical mammograph was upgraded to improve its overall performances and extend its spectral coverage up to 1060 nm, with the aim of increasing the measurement sensitivity to the content of collagen in breast tissue. Late-gated intensity and reduced scattering images are routinely displayed for diagnostic purposes. Maps of tissue constituents (lipid, water and collagen) and blood parameters (total hemoglobin content and blood oxygenation) are built to highlight spatial changes due to physiological and pathological reasons. The upgraded instrument was tested on tissue phantoms. Then images were collected at 7 wavelengths (635-1060 nm) from 10 healthy volunteers. Average collagen content correlated with breast density whenever x-ray mammograms were available (6 subjects).

Use of a nonlinear perturbation approach for in vivo breast lesion characterization by multiwavelength time-resolved optical mammography

A novel nonlinear perturbation model was successfully applied to the in vivo characterization of breast lesions (cysts and tumors) after detection by multi-wavelength time-resolved optical mammography. The model relies on the method of Padé approximants and consists in a nonlinear approximation of time-resolved transmittance curves in the presence of an inclusion. Tissue constituents (blood volume, blood oxygen saturation, lipids and water content) were estimated for both the bulk and the lesion areas. Cysts were reported to have high water content while tumors showed increased blood content as compared to bulk tissue.

Noninvasive assessment of breast cancer risk using time-resolved diffuse optical spectroscopy.

Breast density is a recognized strong and independent risk factor for breast cancer. We propose the use of time-resolved transmittance spectroscopy to estimate breast tissue density and potentially provide even more direct information on breast cancer risk. Time-resolved optical mammography at seven wavelengths (635 to 1060 nm) is performed on 49 subjects. Average information on breast tissue of each subject is obtained on oxy- and deoxyhemoglobin, water, lipids, and collagen content, as well as scattering amplitude and power. All parameters, except for blood volume and oxygenation, correlate with mammographic breast density, even if not to the same extent. A synthetic optical index proves to be quite effective in separating different breast density categories. Finally, the estimate of collagen content as a more direct means for the assessment of breast cancer risk is discussed.

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.