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.

Accuracy and reproducibility of tumor positioning during prolonged and multi-modality animal imaging studies.

Dedicated small-animal imaging devices, e.g. positron emission tomography (PET), computed tomography (CT) and magnetic resonance imaging (MRI) scanners, are being increasingly used for translational molecular imaging studies. The objective of this work was to determine the positional accuracy and precision with which tumors in situ can be reliably and reproducibly imaged on dedicated small-animal imaging equipment. We designed, fabricated and tested a custom rodent cradle with a stereotactic template to facilitate registration among image sets. To quantify tumor motion during our small-animal imaging protocols, 'gold standard' multi-modality point markers were inserted into tumor masses on the hind limbs of rats. Three types of imaging examination were then performed with the animals continuously anesthetized and immobilized: (i) consecutive microPET and MR images of tumor xenografts in which the animals remained in the same scanner for 2 h duration, (ii) multi-modality imaging studies in which the animals were transported between distant imaging devices and (iii) serial microPET scans in which the animals were repositioned in the same scanner for subsequent images. Our results showed that the animal tumor moved by less than 0.2-0.3 mm over a continuous 2 h microPET or MR imaging session. The process of transporting the animal between instruments introduced additional errors of approximately 0.2 mm. In serial animal imaging studies, the positioning reproducibility within approximately 0.8 mm could be obtained.

Benign versus malignant breast masses: optical differentiation with US-guided optical imaging reconstruction.

PURPOSE: To investigate prospectively the feasibility of using optical tomography with ultrasonographic (US) localization to differentiate malignant from benign breast masses and to compare optical tomography with color Doppler US. MATERIALS AND METHODS: The study was approved by the local internal review board committee and by the Human Subjects Research Review Board of Army Medical Research and Materiel Command. Signed informed consent was obtained, and the study was HIPAA compliant. Between May 2003 and March 2004, 65 consecutive women (mean age, 51 years; age range, 24-80 years) with 81 breast lesions underwent US-guided biopsy and were scanned with a combined imager. The hand-held probe, which consisted of a centrally located US transducer surrounded by near-infrared sensors, was used to simultaneously acquire coregistered US images and optical data. The lesion location obtained at US was used to guide optical imaging reconstruction. Light absorption was measured at two wavelengths. From these measurements, tumor angiogenesis was assessed on the basis of calculated total hemoglobin concentration. A Student t distribution was used to calculate the statistical significance of mean maximum and mean average hemoglobin concentrations obtained in malignant and benign lesion groups, and P < .001 was considered to indicate a statistically significant difference. RESULTS: Biopsy results revealed eight early stage invasive carcinomas (malignant group) and 73 benign lesions (benign group). The mean maximum and mean average hemoglobin concentrations in the malignant group were 122 micromol/L +/- 26.8 (+/- standard deviation) and 88 micromol/L +/- 24.5, respectively. The mean maximum and mean average hemoglobin concentrations in the benign group were 55 micromol/L +/- 24.8 and 38 micromol/L +/- 17.4, respectively. Both the maximum and average total hemoglobin concentrations were significantly higher in the malignant group compared with the benign group (P < .001). When a maximum hemoglobin concentration of 95 micromol/L was used as the threshold value, the sensitivity, specificity, positive predictive value, and negative predictive value of optical tomography were 100%, 96%, 73%, and 100%, respectively, and the sensitivity, specificity, positive predictive value, and negative predictive value of color Doppler US were 63%, 69%, 19%, and 94%, respectively. CONCLUSION: Findings indicate that optical tomography with US localization is feasible for differentiating benign and early stage malignant breast lesions.

Utilizing optical tomography with ultrasound localization to image heterogeneous hemoglobin distribution in large breast cancers.

PURPOSE: Angiogenesis in advanced breast cancers is highly distorted and heterogeneous. Noninvasive imaging that can monitor angiogenesis may be invaluable initially for diagnosis and then for assessing tumor response to treatment. By combining ultrasound (US) and near-infrared (NIR) optical imaging, a reliable new technique has emerged for localizing and characterizing tumor angiogenesis within the breast. METHODS: This new technique employs a commercial US transducer coupled with an array of NIR optical fibers mounted on a hand-held probe. The US image is used for lesion localization and for guiding optical imaging reconstruction. Optical sensors are used for imaging tumor total hemoglobin distribution, which is directly related to tumor angiogenesis. RESULTS: Six large breast carcinomas were studied and microvessel density count was then performed on tissue samples obtained from these cancers. Two patients had locally advanced breast cancers and received neoadjuvant chemotherapy for 3 months. In one patient, before chemotherapy, the total hemoglobin distribution showed a high concentration at the cancer periphery; the distribution was later confined to the core area after 3 months of treatment. In another patient, as treatment progressed, the maximum hemoglobin concentration decreased from 255.3, to 147.5, to 76.9 micromol/l with an associated reduction in spatial extension. The other four patients had cancers of 2.0 to 3.0 cm in size and were imaged either at the time of core biopsy or definitive surgery. The histologic microvessel density counts from these tumor samples correlate to hemoglobin distributions with a correlation coefficient of 0.64 (P < .05). CONCLUSION: These initial results suggest that this new imaging technique may have great potential in imaging the heterogeneous vascular distribution of larger breast cancers in vivo and in monitoring treatment-related changes in angiogenesis during chemotherapy.

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.

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.

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.