Minming Huang

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.

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.

Dual-mesh optical tomography reconstruction method with a depth correction that uses A priori ultrasound information

A dual-mesh reconstruction method with a depth correction for near-infrared diffused wave imaging with ultrasound localization is demonstrated by use of phantoms and clinical cancer cases. Column normalization is applied to the weight matrix obtained from the Born approximation to correct the depth-dependent problem in the reconstructed absorption maps as well as in the total hemoglobin concentration maps. With the depth correction, more uniform absorption maps for target layers at different depths are obtained from the phantoms, and the correlation between the reconstructed hemoglobin concentration maps of deeply located, large cancers and the histological microvessel density counts are dramatically improved.

Simultaneous reconstruction of absorption and scattering maps with ultrasound localization: feasibility study using transmission geometry

We report the experimental results of the simultaneous reconstruction of absorption and scattering coefficient maps with ultrasound localization. Near-infrared (NIR) data were obtained from frequency domain and dc systems with source and detector fibers configured in transmission geometry. High- or low-contrast targets located close to either the boundary or the center of the turbid medium were reconstructed by using NIR data only and NIR data with ultrasound localization. Results show that the mean reconstructed absorption coefficient and the spatial distribution of the absorption map have been improved significantly with ultrasound localization. The improvements in the mean scattering coefficient and the spatial distribution of the scattering coefficient are moderate. When both the absorption and the scattering coefficients are reconstructed the performance of the frequency-domain systemis much better than that of the dc system.

Effect of the chest wall on breast lesion reconstruction

The chest wall underneath the breast tissue affects near-infrared (NIR) diffusive waves measured with reflection geometry. With the assistance of a co-registered ultrasound, the depth and the tilting angle of the chest wall can be determined and are used to model the breast as a two-layer medium. Finite element method (FEM) is suitable for modeling complex boundary conditions and is adapted to model the breast tissue and chest wall. Four parameters of bulk absorption and reduced scattering coefficients of these two layers are estimated and used for imaging reconstruction. Using a two-layer model, we have systematically investigated the effect of the chest wall on breast lesion reconstruction. Results have shown that chest-wall depth, titling angle, and difference between optical properties of two layers of lesion and reference sites affect the lesion reconstruction differently. Our analysis will be valuable and informative to researchers who are using reflectance geometry for breast imaging. The analysis can also provide guidelines for imaging operators to minimize image artifacts and to produce the best reconstruction results.

An optical tomography method that accounts for a titled chest-wall in breast imaging

The chest-wall underneath the breast tissue distorts the diffused near infra-red light measured at distant source-detector pairs. Common image reconstruction method consider the media as homogeneous and applying the semi-infinite model. In this paper, we have compared the performance of our two-layer model with semi-infinite model by simulation and a clinical case. The results show that when the chest wall has significant effect on the measurement data, a benign lesion with low absorption can be misled as a malignant case with high absorption by using semi-infinite model. We have also shown the influence of mismatch geometry of breast tissue and chest-wall at lesion and reference sides on the reconstructed image and a correction method has been introduced to reduce these effects. With the assistance of two orthogonal co-registered ultrasounds, the geometry of the breast tissue and chest wall interface can be determined and modeled as a two-layer medium with 3D finite element mesh. Since numerical algorithms based on finite element methods (FEM) are suitable for complex geometry and boundary conditions, this method is adapted to model the chestwall. Four parameters of bulk absorption and reduced scattering coefficients of the first and second layers are estimated and used to characterize the optical properties of the medium. We used a finite element model based on modified born approximation for image reconstruction. A mismatch correction algorithm has been applied to compensate the mismatch geometry of the breast tissue and chest-wall interface at the reference and the lesion side.

Three-dimensional simultaneous absorption and scattering coefficient reconstruction for reflection geometry

In this paper, a 3D dual-mesh imaging reconstruction method is demonstrated, which can reconstruct absorption and scattering coefficients simultaneously. In the dual-mesh scheme, the total number of voxels with unknown absorption and scattering perturbations are maintained on the same order of total measurements by using a fine grid for target region and a coarse grid for background region. Certain row/column normalization has been applied to alleviate the crosstalk between the absorption coefficient and scattering coefficient, and to minimize the depth dependent problem. Experimental results of targets with different absorption and scattering contrasts have shown that accurate reconstruction of both absorption and scattering coefficients can be achieved.

2-D NIR imaging reconstruction with ultrasound guidance

The imaging reconstruction of near infrared (NIR) diffusive light is in general underdetermined and ill-posed. We have proposed a novel combined approach by using a priori knowledge acquired from co-registered ultrasound to overcome the NIR inversion problem. In this paper we report simulation and experimental results on combined imaging, and we show that NIR reconstruction with the aid of co-registered ultrasound is well defined and the reconstructed optical properties are more accurate than NIR imaging alone.

A two-layer model for NIR breast imaging with the assistance of ultrasound

The chest-wall layer underneath the breast tissue consists of muscle layer and induces distortion to measured near infrared diffused wave when the patient is imaged in the supine position. In this paper, we present results of using a simple two-layer model to correct the chest wall induced distortion. Four parameters of absorption and reduced scattering coefficients of both layers are used to describe the optical properties of the model. With the initially estimated absorption and reduced scattering coefficients, an iterative search method is used to find the best fitted parameters to minimize the difference between the measurements obtained at normal breast region and the model data. Then, a correction method is applied to correct the chest wall mismatch between the lesion site and reference site. With this correction scheme, phantom targets located on top of the chest-wall phantom layer can be reconstructed with good contrast and resolution. With the a priori chest wall depth information obtained from ultrasound at both normal and lesion regions, the contrast between malignant breast cancers and benign lesions can be further improved compared with that obtained from the modified Born approximation, where semi-infinite boundary is used.

Tumor angiogenesis and tumor hypoxia as diagnostic indices for differentiation of benign versus malignant breast masses

In this report, clinical examples of using combined ultrasound and optical diffused wave technique to image tumor total hemoglobin concentration and tumor hypoxia are given. These examples demonstrate that the sensitivity and specificity of using tumor hemoglobin level as diagnostic index are much higher than that of tumor hypoxia.