Nanguang Chen

Ultrasound-guided optical tomographic imaging of malignant and benign breast lesions: initial clinical results of 19 cases.

The diagnosis of solid benign and malignant tumors presents a unique challenge to all noninvasive imaging modalities. Ultrasound is used in conjunction with mammography to differentiate simple cysts from solid lesions. However, the overlapping appearances of benign and malignant lesions make ultrasound less useful in differentiating solid lesions, resulting in a large number of benign biopsies. Optical tomography using near-infrared diffused light has great potential for imaging functional parameters of 1) tumor hemoglobin concentration, 2) oxygen saturation, and 3) metabolism, as well as other tumor distinguishing characteristics. These parameters can differentiate benign from malignant lesions. However, optical tomography, when used alone, suffers from low spatial resolution and target localization uncertainty due to intensive light scattering. Our aim is to combine diffused light imaging with ultrasound in a novel way for the detection and diagnosis of solid lesions. Initial findings of two early-stage invasive carcinomas, one combined fibroadenoma and fibrocystic change with scattered foci of lobular neoplasia/lobular carcinoma in situ, and 16 benign lesions are reported in this paper. The invasive cancer cases reveal about two-fold greater total hemoglobin concentration (mean 119 micromol) than benign cases (mean 67 micromol), and suggest that the discrimination of benign and malignant breast lesions might be enhanced by this type of achievable optical quantification with ultrasound localization. Furthermore, the small invasive cancers are well localized and have wavelength-dependent appearance in optical absorption maps, whereas the benign lesions appear diffused and relatively wavelength-independent.

Imaging tumor angiogenesis by use of combined near-infrared diffusive light and ultrasound

A novel two-step reconstruction scheme using a combined near-infrared and ultrasound technique and its utility in imaging distributions of optical absorption and hemoglobin concentration of breast lesions are demonstrated. In the first-step image reconstruction, the entire tissue volume is segmented based on initial coregistered ultrasound measurements into lesion and background regions. Reconstruction is performed by use of a finer grid for lesion region and a coarse grid for the background tissue. As a result, the total number of voxels with unknown absorption can be maintained on the same order of total measurements, and the matrix with unknown total absorption distribution is appropriately scaled for inversion. In the second step, image reconstruction is refined by optimization of lesion parameters measured from ultrasound images. It is shown that detailed distributions of wavelength-dependent absorption and hemoglobin concentration of breast carcinoma can be obtained with the new reconstruction scheme.

Reconstruction for free-space fluorescence tomography using a novel hybrid adaptive finite element algorithm

With the development of in-vivo free-space fluorescence molecular imaging and multi-modality imaging for small animals, there is a need for new reconstruction methods for real animal-shape models with a large dataset. In this paper we are reporting a novel hybrid adaptive finite element algorithm for fluorescence tomography reconstruction, based on a linear scheme. Two different inversion strategies (Conjugate Gradient and Landweber iterations) are separately applied to the first mesh level and the succeeding levels. The new algorithm was validated by numerical simulations of a 3-D mouse atlas, based on the latest free-space setup of fluorescence tomography with 360 degrees geometry projections. The reconstructed results suggest that we are able to achieve high computational efficiency and spatial resolution for models with irregular shape and inhomogeneous optical properties.

Simultaneous near-infrared diffusive light and ultrasound imaging

We have constructed a near-real-time combined imager suitable for simultaneous ultrasound and near-infrared diffusive light imaging and coregistration. The imager consists of a combined hand-held probe and the associated electronics for data acquisition. A two-dimensional ultrasound array is deployed at the center of the combined probe, and 12 dual-wavelength laser source fibers (780 and 830 nm) and 8 optical detector fibers are deployed at the periphery. We have experimentally evaluated the effects of missing optical sources in the middle of the combined probe on the accuracy of the reconstructed optical absorption coefficient and assessed the improvements of a reconstructed absorption coefficient with the guidance of the coregistered ultrasound. The results have shown that, when the central ultrasound array area is in the neighborhood of 2 cm x 2 cm, which corresponds to the size of most commercial ultrasound transducers, the optical imaging is not affected. The results have also shown that the iterative inversion algorithm converges quickly with the guidance of a priori three-dimensional target distribution, and only one iteration is needed to reconstruct an accurate optical absorption coefficient.

A two axes scanning SOI MEMS micromirror for endoscopic bioimaging

A novel silicon on insulator (SOI) MEMS process has been designed and developed to realize a two axes thermally actuated single crystal silicon micromirror device, which consists of a mirror plate, four flexural springs and four thermal actuators. The mirror plate has the same thickness as a SOI device layer i.e. 4 µm. The SOI layer is selectively thinned down to 2 µm for fabricating flexural springs and thermal actuators. The thinning of the SOI layer is essential to lower (control) the flexural rigidity of the springs and the actuators and thus to achieve a higher tilt angle at low thermal power. The developed single wafer process is based on dry reactive ion etching CMOS compatible chemistries. The minimum chip size design of 1 mm × 1 mm has a 400 µm diameter mirror plate. Other chip designs include the mirror diameters in the range from 200 to 500 µm. This paper also presents a study on the mirror plate curvature, thermal actuation mechanism and the experimental results. The measured maximum angular deflection achieved was 17° at an operating applied voltage of less than 2 V, and the radius of curvature of the mirror plate was in the range from 20 to 50 mm. The micromirror was developed for a miniature catheter optical probe for optical coherence tomography in vivo imaging. A low cross-sectional size of the probe and higher resolution are essential for investigating inaccessible pathologies in vivo. This required a compact micromirror chip and yet sufficiently large mirror plate (typically ~500 µm or more), this trade-off was the key motivation for the research presented in this paper.

Focal modulation microscopy

We report a novel light microscopy method for high resolution molecular imaging of thick biological tissues with one photon excited fluorescence. Effective optical sectioning and diffraction limited spatial resolution are achieved when imaging deep inside a multiple-scattering medium by the use of focal modulation, a technique for suppressing the background fluorescence signal excited by scattered light. Our method has been validated with animal tissue and an imaging depth around 600 microns has been demonstrated.

Binary-phase spatial filter for real-time swept-source optical coherence microscopy

We report a novel scheme to optimize the focusing condition for real-time, swept-source optical coherence microscopy. The axial and lateral behaviors of four-zone binary-phase spatial filters are presented numerically. A nearly constant axial intensity distribution along an extended depth of focus of 1.5 mm and a lateral resolution of 5 microm are experimentally verified. The A-line scan rate is up to 16 kHz, yielding a frame rate of 25 Hz and 640 lines per image.

Design and development of a 3D scanning MEMS OCT probe using a novel SiOB package assembly

A MEMS optical coherence tomography (OCT) probe prototype was developed using a unique assembly based on silicon optical bench (SiOB) methodology. The probe is formed by integrating a three-dimensional (3D) scanning micromirror, gradient refractive index (GRIN) lens and optical fiber on SiOB substrates having prefabricated self-aligned slots. The two-axis scanning micromirror is based on electrothermal actuation with required voltage less than 2 V for mechanical deflections up to 17°. The optical probe was enclosed within a biocompatible, transparent and waterproof polycarbonate tube with a view of in vivo diagnostic applications. The diameter of the miniature probe is less than 4 mm and the length of its rigid part is about 25 mm. The probe engineering and proof of concept of the probe were demonstrated by obtaining en face and three-dimensional OCT images of an IR card used as a standard sample.

Portable near-infrared diffusive light imager for breast cancer detection

We present a frequency-domain near-infrared optical tomography system designed for breast cancer detection, in conjunction with conventional ultrasound. It features fast optical switching, three-wavelength excitations, and avalanche photodiode as detectors. Laser diodes at 660, 780, and 830 nm are used as light sources and their outputs are distributed sequentially to one of nine source fibers. An equivalent 130-dB isolation between electrical signals from different source channels is achieved with the optical switches of very low crosstalk. Ten detection channels, each of which includes a silicon avalanche photodiode, detect diffusive photon density waves simultaneously. The dynamic range of an avalanche photodiode is about 20 to 30 dB higher than that of a photomultiplier tube, thus eliminating the need for multistep system gain control. The entire system is compact in size (<0.051 m(3)) and fast in data acquisition (less than 2 sec for a complete scan). Calibration and the clinical experiment results are presented in the paper.

Ultra long high resolution beam by multi-zone rotationally symmetrical complex pupil filter.

An ultra long high resolution beam with extension of depth of focus (DoF) in the axial direction as well as high resolution in the transverse direction has been demonstrated by a seven-zone rotationally symmetrical complex pupil filter imposed at the aperture of a focusing lens. Both amplitude and phase of the transmitted light are modulated in different zones. The scalar diffraction theory is used to optimize the zone parameters. Simulation results show that extended DoF of the beam is increased by 16 times while the spot size at the beam waist is reduced to 0.7 times.