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Biomedical subjects

Michael S Feld

Publications and source records attributed to Michael S Feld.

At least 19 recordsLinked to original sources
PubMed2007

Constrained regularization: hybrid method for multivariate calibration.

We present a hybrid multivariate calibration method, constrained regularization (CR), and demonstrate its utility via numerical simulations and experimental Raman spectra. In this new method, multivariate calibration is treated as an inverse problem in which an optimal balance between model complexity and noise rejection is achieved with the inclusion of prior information in the form of a spectral constraint. A key feature is that the constraint is incorporated in a flexible manner, allowing the minimization algorithm to arrive at the optimal solution. We demonstrate that CR, when used with an appropriate constraint, is superior to methods without prior information, such as partial least-squares, and is less susceptible to spurious correlations. In addition, we show that CR is more robust than methods in which the constraint is rigidly incorporated, such as hybrid linear analysis, when the exact spectrum of the analyte of interest as it appears in the sample is not available. This situation can occur as a result of experimental or sample variations and often arises in complex or turbid samples such as biological tissues.

Algorithms↗
PubMed2006

Optical measurement of cell membrane tension.

Using a novel noncontact technique based on optical interferometry, we quantify the nanoscale thermal fluctuations of red blood cells (RBCs) and giant unilamellar vesicles (GUVs). The measurements reveal a nonvanishing tension coefficient for RBCs, which increases as cells transition from a discocytic shape to a spherical shape. The tension coefficient measured for GUVs is, however, a factor of 4-24 smaller. By contrast, the bending moduli for cells and vesicles have similar values. This is consistent with the cytoskeleton confinement model, in which the cytoskeleton inhibits membrane fluctuations [Gov et al., Phys. Rev. Lett. 90, 228101, (2003).

Biophysical Phenomena↗
PubMed2006

Assessing epithelial cell nuclear morphology by using azimuthal light scattering spectroscopy.

We describe azimuthal light scattering spectroscopy (phi/LSS), a novel technique for assessing epithelial-cell nuclear morphology. The difference between the spectra measured at azimuthal angles phi = 0 degrees and phi = 90 degrees preferentially isolates the single backscattering contribution due to large (approximately 10 microm) structures such as epithelial cell nuclei by discriminating against scattering from smaller organelles and diffusive background. We demonstrate the feasibility of using phi/LSS for cancer detection by showing that spectra from cancerous colon tissue exhibit significantly greater azimuthal asymmetry than spectra from normal colonic tissues.

Cell Nucleus↗
PubMed2006

Tissue self-affinity and polarized light scattering in the born approximation: a new model for precancer detection.

Light scattered from biological tissues can exhibit an inverse power law spectral component. We develop a model based on the Born approximation and von Karman (self-affine) spatial correlation of submicron tissue refractive index to account for this. The model is applied to light scattering spectra obtained from excised esophagi of normal and carcinogen-treated rats. Power law exponents used to fit dysplastic tissue site spectra are significantly smaller than those from normal sites, indicating that changes in tissue self-affinity can serve as a potential biomarker for precancer.

Algorithms↗
PubMed2006

Live cell refractometry using microfluidic devices.

Using Hilbert phase microscopy for extracting quantitative phase images, we measured the average refractive index associated with live cells in culture. To decouple the contributions to the phase signal from the cell refractive index and thickness, we confined the cells in microchannels. The results are confirmed by comparison with measurements of spherical cells in suspension.

Cell Shape↗
PubMed2006

Intrinsic fluorescence and diffuse reflectance spectroscopy identify superficial foam cells in coronary plaques prone to erosion.

OBJECTIVE: Foam cells perform critical functions in atherosclerosis. We hypothesize that coronary segments with superficial foam cells (SFCs) situated in a region of interest with a depth of 200 mum can be identified using intrinsic fluorescence spectroscopy (IFS) and diffuse reflectance spectroscopy (DRS). This is a key step in our ongoing program to develop a spectroscopic technique for real-time in vivo diagnosis of vulnerable atherosclerotic plaque. METHODS AND RESULTS: We subjected 132 human coronary segments to in vitro IFS and DRS. We detected SFCs in 13 thick fibrous cap atheromas and 8 pathologic intimal thickening (PIT) lesions. SFCs colocalized with accumulations of smooth muscle cells and proteoglycans, including hyaluronan (P<0.001). Two spectroscopic parameters were generated from analysis of IFS at 480 nm excitation and DRS. A discriminatory algorithm using these parameters identified specimens with SFC area >40%, 20%, 10%, 5%, 2.5%, and 0% of the region of interest with 98%, 98%, 93%, 94%, 93%, and 90% accuracy, respectively. CONCLUSIONS: Our combined IFS and DRS technique accurately detects SFCs in thick fibrous cap atheromas and PIT lesions. Because SFCs are associated with histological markers of plaque erosion, our spectroscopic technique could prove useful in identifying vulnerable plaques.

Algorithms↗
PubMed2006

In vivo margin assessment during partial mastectomy breast surgery using raman spectroscopy.

We present the first demonstration of in vivo collection of Raman spectra of breast tissue. Raman spectroscopy, which analyzes molecular vibrations, is a promising new technique for the diagnosis of breast cancer. We have collected 31 Raman spectra from nine patients undergoing partial mastectomy procedures to show the feasibility of in vivo Raman spectroscopy for intraoperative margin assessment. The data was fit with an established model, resulting in spectral-based tissue characterization in only 1 second. Application of our previously developed diagnostic algorithm resulted in perfect sensitivity and specificity for distinguishing cancerous from normal and benign tissues in our small data set. Significantly, we have detected a grossly invisible cancer that, upon pathologic review, required the patient to undergo a second surgical procedure. Had Raman spectroscopy been used in a real-time fashion to guide tissue excision during the procedure, the additional reexcision surgery might have been avoided. These preliminary findings suggest that Raman spectroscopy has the potential to lessen the need for reexcision surgeries resulting from positive margins and thereby reduce the recurrence rate of breast cancer following partial mastectomy surgeries.

Breast Neoplasms↗
PubMed2006

Diffraction phase microscopy for quantifying cell structure and dynamics.

We have developed diffraction phase microscopy as a new technique for quantitative phase imaging of biological structures. The method combines the principles of common path interferometry and single-shot phase imaging and is characterized by subnanometer path-length stability and millisecond-scale acquisition time. The potential of the technique for quantifying nanoscale motions in live cells is demonstrated by experiments on red blood cells.

Cell Movement↗
PubMed2005

Diagnosing breast cancer by using Raman spectroscopy.

We employ Raman spectroscopy to diagnose benign and malignant lesions in human breast tissue based on chemical composition. In this study, 130 Raman spectra are acquired from ex vivo samples of human breast tissue (normal, fibrocystic change, fibroadenoma, and infiltrating carcinoma) from 58 patients. Data are fit by using a linear combination model in which nine basis spectra represent the morphologic and chemical features of breast tissue. The resulting fit coefficients provide insight into the chemical/morphological makeup of the tissue and are used to develop diagnostic algorithms. The fit coefficients for fat and collagen are the key parameters in the resulting diagnostic algorithm, which classifies samples according to their specific pathological diagnoses, attaining 94% sensitivity and 96% specificity for distinguishing cancerous tissues from normal and benign tissues. The excellent results demonstrate that Raman spectroscopy has the potential to be applied in vivo to accurately classify breast lesions, thereby reducing the number of excisional breast biopsies that are performed.

Adipose Tissue↗
PubMed2005

Hilbert phase microscopy for investigating fast dynamics in transparent systems.

We introduce Hilbert phase microscopy (HPM) as a novel optical technique for measuring high transverse resolution quantitative phase images associated with optically transparent objects. Because of its single-shot nature, HPM is suitable for investigating rapid phenomena that take place in transparent structures such as biological cells. The potential of this technique for studying biological systems is demonstrated with measurements of red blood cells, and its ability to quantify dynamic processes on a millisecond scale is exemplified with measurements of evaporating micrometer-sized water droplets.

Computer Systems↗
PubMed2005

Correlation and cross-linking effects in imprinting sites for divalent adsorption in gels.

We examine a method to mimic active sites in proteins by chemical imprinting of p-valent templates in heteropolymer gels. Previous studies have confirmed successful formation of sites by adsorption of targets with p >/= 2 contacts. We investigate the recovery of sites with p = 2 imprinted by lead methacrylate Pb(MAAc)(2) (placing two carboxyl groups in close proximity). The improved binding ability of gels with more cross-links, and the relative insensitivity to changes in gel volume contradict simple theory. We conclude that adsorber pairs are predominantly located on the same polymer chain, posing a challenge to mimicking protein-like function.

Adsorption↗
PubMed2005

Harmonic phase-dispersion microscope with a Mach-Zehnder interferometer.

Harmonic phase-dispersion microscopy (PDM) is a new imaging technique in which contrast is provided by differences in refractive index at two harmonically related wavelengths. We report a new configuration of the harmonic phase-dispersion microscope in a Mach-Zehnder geometry as an instrument for imaging biological samples. Several improvements on the earlier design are demonstrated, including a single-pass configuration and acousto-optic modulators for generating the heterodyne signals without mechanical arm scanning. We demonstrate quantitative phase-dispersion images of test structures and biological samples.

Equipment Design↗
PubMed2004

Fourier phase microscopy for investigation of biological structures and dynamics.

By use of the Fourier decomposition of a low-coherence optical image field into two spatial components that can be controllably shifted in phase with respect to each other, a new high-transverse-resolution quantitative-phase microscope has been developed. The technique transforms a typical optical microscope into a quantitative-phase microscope, with high accuracy and a path-length sensitivity of lambda/5500, which is stable over several hours. The results obtained on epithelial and red blood cells demonstrate the potential of this instrument for quantitative investigation of the structure and dynamics associated with biological systems without sample preparation.

Cells, Cultured↗
PubMed2004

Noncontact measurement of nerve displacement during action potential with a dual-beam low-coherence interferometer.

We have used a novel phase-referenced heterodyne dual-beam low-coherence interferometer to perform what we believe are the first noncontact measurements of surface motion in a nerve bundle during the action potential. Nerve displacements of approximately 5-nm amplitude and approximately 10-ms duration are measured without signal averaging. This interferometer may find general application in measurement of small motion in cells and other weakly scattering samples.

Action Potentials↗
PubMed2004

Optical fiber probe for biomedical Raman spectroscopy.

In vitro experiments have demonstrated the ability of Raman spectroscopy to diagnose a wide variety of diseases. Recent in vivo investigations performed with optical fiber probes were promising but generally limited to easily accessible organs, often requiring relatively long collection times. We have implemented an optical design strategy to utilize system throughput fully by characterizing the Raman distribution from tissue. This scheme optimizes collection efficiency, minimizes noise, and has resulted in small-diameter, highly efficient Raman probes that are capable of collecting high-quality data in 1 s. Performance has been tested through simulations and experiments with tissue models and several in vitro tissue types, demonstrating that this new design can advance Raman spectroscopy as a clinically practical technique.

Aorta↗
PubMed2004

The combined use of fluorescence, reflectance, and light-scattering spectroscopy for evaluating dysplasia in Barrett's esophagus.

Intrinsic fluorescence, diffuse reflectance, and light-scattering spectroscopy provide complementary information on biochemical and morphologic information extending potentially from the molecular to the tissue level. Model-based spectral analysis in each case yields results about specific tissue parameters in a quantitative manner.Preliminary studies demonstrate that these parameters can be used for the development of algorithms that can detect dysplastic changes in patients with Barrett's esophagus (BE) with high sensitivity and specificity. Studies validating tri-modal spectroscopy based algorithms and real-time spectroscopic data analysis are under way to provide a more accurate and extensive assessment of the potential of this approach as a clinical noninvasive tool that could improve the management and treatment of BE dysplasia.

Barrett Esophagus↗
PubMed2004

Spectroscopic diagnosis and imaging of invisible pre-cancer.

The theme of this paper is the use of optical spectroscopy to diagnose invisible pre-cancer in patients undergoing endoscopy and similar medical procedures. We describe three techniques that provide diagnostic information and two instruments to implement them, the FastEEM for studying small regions of tissue and the LSS (light scattering spectroscopy) imaging system for wide-area surveillance. The FastEEM is an optical fiber clinical device that collects spectra of reflected light and fluorescence at multiple excitation wavelengths from the tissue, all in a fraction of a second. Quantitative information is obtained in real time, without removing the tissue and without the need for staining and fixation. Three types of spectral information are extracted intrinsic fluorescence, diffuse reflectance and elastic light scattering. Each of the three analyses is based on a biophysical model, and each provides complementary quantitative physical and chemical information about cellular/tissue structures. This information is used to make a combined spectral diagnosis, a method we call tri-modal spectroscopy (TMS). Promising clinical studies are being carried out on patients undergoing routine pre-cancer surveillance in the oral cavity, the uterine cervix and the gastrointestinal tract. The LSS imaging system provides wide-area spectroscopic images of the epithelium, typically 2 cm in each dimension, depicting the size distribution and chromatin content of the cell nuclei, which are key parameters in diagnosing pre-cancer. This instrument is in preclinical stages of development, although a laboratory prototype has been used to create diagnostic images in resected colon polyp samples. The combination of the TMS/FastEEM and LSS imaging instrument will constitute a powerful new diagnostic tool, with LSS imaging to provide wide area surveillance and the TMS probe to provide detailed information on suspect tissue sites.

Cervix Uteri↗