Research Fellow @ Massachusetts Institute of Technology, Transfusion Medicine Fellow @ Dartmouth-Hitchcock Medical Center

Portable real-time optical coherence tomography system for intraoperative imaging and staging of breast cancer

Breast cancer continues to be one of the most widely diagnosed forms of cancer amongst women and the second leading type of cancer deaths amongst women. The recurrence rate of breast cancer is highly dependent on several factors including the complete removal of the primary tumor and the presence of cancer cells in involved lymph nodes. The metastatic spread and staging of breast cancer is also evaluated through the nodal assessment of the regional lymphatic system. A portable real-time spectral domain optical coherence tomography system is being presented as a clinical diagnostic tool in the intraoperative delineation of tumor margins as well as for real time lymph node assessment. The system employs a super luminescent diode centered at 1310 nm with a bandwidth of 92 nm. Using a spectral domain detection system, the data is acquired at a rate of 5 KHz / axial scan. The sample arm is a galvanometer scanning telecentric probe with an objective lens (f = 60 mm, confocal parameter = 1.5 mm) yielding an axial resolution of 8.3 μm and a transverse resolution of 35.0 μm. Images of tumor margins are acquired in the operating room ex vivo on freshly excised human tissue specimen. This data shows the potential of the use of OCT in defining the structural tumor margins in breast cancer. Images taken from ex-vivo samples on the bench system clearly delineate the differences between clusters of tumor cells and nearby adipose cells. In addition, the data shows the potential for OCT as a diagnostic tool in the staging of cancer metastasis through locoregional lymph node assessment.

Needle-probe system for the measurement of tissue refractive index

Needle-based devices, which are in wide clinical use for needle biopsy procedures, may be augmented by suitable optical techniques for the localization and diagnosis of diseased tissue. Tissue refractive index is one optical contrast mechanism with diagnostic potential. In the case of mammary tissue, for example, recent research indicates that refractive index variations between tissue types may be useful for the identification of cancerous tissue. While many coherence-based forward-sensing devices have been developed to detect scattering changes, none have demonstrated refractive index measurement capabilities. We present a novel needle-based device that is capable of simultaneously measuring refractive index and scattering. Coupled to the sample arm of an optical coherence tomography system, the needle device detects the scattering response and optical pathlength through tissue residing in a fixed-width channel. Near-infrared measurements of tissues and materials with known optical properties using a prototype device will be presented. This work demonstrates the feasibility of integrated in vivo measurement of refractive index and scattering in conjunction with existing clinical needle-based devices.

Interferometric synthetic aperture microscopy
Publication

Interferometric synthetic aperture microscopy

State-of-the-art methods in high-resolution three-dimensional optical microscopy require that the focus be scanned through the entire region of interest. However, an analysis of the physics of the light-sample interaction reveals that the Fourier-space coverage is independent of depth. Here we show that, by solving the inverse scattering problem for interference microscopy, computed reconstruction yields volumes with a resolution in all planes that is equivalent to the resolution achieved only at the focal plane for conventional high-resolution microscopy. In short, the entire illuminated volume has spatially invariant resolution, thus eliminating the compromise between resolution and depth of field. We describe and demonstrate a novel computational image-formation technique called interferometric synthetic aperture microscopy (ISAM). ISAM has the potential to broadly impact real-time three-dimensional microscopy and analysis in the fields of cell and tumour biology, as well as in clinical diagnosis where imaging is preferable to biopsy.

Publication

Optical biopsy of lymph node morphology using optical coherence tomography

Optical diagnostic imaging techniques are increasingly being used in the clinical environment, allowing for improved screening and diagnosis while minimizing the number of invasive procedures. Diffuse optical tomography, for example, is capable of whole-breast imaging and is being developed as an alternative to traditional X-ray mammography. While this may eventually be a very effective screening method, other optical techniques are better suited for imaging on the cellular and molecular scale. Optical Coherence Tomography (OCT), for instance, is capable of high-resolution cross-sectional imaging of tissue morphology. In a manner analogous to ultrasound imaging except using optics, pulses of near-infrared light are sent into the tissue while coherence-gated reflections are measured interferometrically to form a cross-sectional image of tissue. In this paper we apply OCT techniques for the high-resolution three-dimensional visualization of lymph node morphology. We present the first reported OCT images showing detailed morphological structure and corresponding histological features of lymph nodes from a carcinogen-induced rat mammary tumor model, as well as from a human lymph node containing late stage metastatic disease. The results illustrate the potential for OCT to visualize detailed lymph node structures on the scale of micrometastases and the potential for the detection of metastatic nodal disease intraoperatively.

Publication

Color-blind fluorescence detection for four-color DNA sequencing

We present an approach called pulsed multiline excitation (PME) for measurements of multicomponent, fluorescence species and demonstrate its application in capillary electrophoresis for DNA sequencing. To fully demonstrate the advantages of PME, a fluorescent dye set has been developed whose absorption maxima span virtually the entire visible spectrum. Unlike emission wavelength-dependent approaches for identifying fluorescent species, the removal of the spectral component in PME confers a number of advantages including higher and normalized signals from all dyes present in the assay, the elimination of spectral cross-talk between dyes, and higher signal collection efficiency. Base-calling is unambiguously determined once dye mobility corrections are made. These advantages translate into significantly enhanced signal quality as illustrated in the primary DNA sequencing data and provide a means for achieving accurate base-calling at lower reagent concentrations.

Computational Analysis of Transition Metal Doped Nanotubes and Their Application to Molecular Electronics

We have previously proposed molecular circuits designed from polyaniline polymer strands, polyacetylene polymer strands and charge transfer salts acting as transistors. Due to unique properties that are demonstrated in this manuscript, we propose the use of carbon single wall nanotubes and transition metal endohedrally doped single wall carbon nanotubes (SWNTs) for utilization in molecular electronics. Different transition metals were used in a systematic fashion to manipulate the molecular orbital energy gap (HOMO-LUMO gap) of metallic (Ch = (n = m)) nanotubes. Gradient corrected, Density Functional Theory (DFT) Self Consistent Field (SCF) calculations were used to calculate molecular orbital energy levels, HOMO-LUMO gaps, electron affinities, ionization energies and other electronic properties for these molecules. The effect that a SWNT’s length has on its HOMO-LUMO gap was investigated. DFT-SCF calculations were also used to demonstrate how multiple metal filled nanotubes could be used to construct a molecular nanotube based transistor.

Publication

Instrumentation for multi-modal spectroscopic diagnosis of epithelial dysplasia

Reflectance and fluorescence spectroscopies have shown great promise for early detection of epithelial dysplasia. We have developed a clinical reflectance spectrofluorimeter for multimodal spectroscopic diagnosis of epithelial dysplasia. This clinical instrument, the FastEEM, collects white light reflectance and fluorescence excitation-emission matrices (EEM’s) within a fraction of a second. In this paper we describe the FastEEM instrumentation, designed for collection of multi-modal spectroscopic data. We illustrate its performance using tissue phantoms with well defined optical properties and biochemicals of known fluorescence properties. In addition, we discuss our plans to develop a system that combines a multi-spectral imaging device for wide area surveillance with this contact probe device.

Electron transfer to oriented molecules: Surprising steric effect in t-butyl bromide

Collisions between neutral K atoms and oriented t-butyl bromide molecules produce the ions K+ and Br− at energies high enough to separate charged particles (≳4 eV). Ions are detected by coincidence tof mass spectrometry for orientation of the t-butyl bromide such that the K atom attacks either the Br end or the t-butyl end of the molecule. At high energies the steric asymmetry factor is larger than that for CH3Br. But at energies near threshold, the steric asymmetry factor reverses sign and attack at the t-butyl end becomes more reactive than attack at the Br end. The electron is apparently transferred into different orbitals at different ends.

Physician-scientist with extensive experience developing and translating nanotechnologies and biomedical optical technologies from the bench to clinic in areas of genetics, oncology, and cardiovascular diseases. Extensive experience in community building in healthcare innovation, research, medical, and physician-scientist communities through various leadership roles.

Research Profiles

Contact