As described earlier, due to intense light scattering, optical tomography alone has not been widely used in clinical studies. Data in the published literature have been limited to feasibility studies or case reports. Pogue et al. [9
] reported pilot results of one invasive ductal carcinoma 1 cm in size and one benign fibroadenoma 3 cm in size. The reported maximum total hemoglobin concentrations were 68 µmol for the cancer case and 55 µmol for the benign case. Although the invasive cancer size reported by this group is comparable to ours, the system they used can only acquire NIR data from a ring area with optical sources and detectors deployed around the breast (2-D imager). Therefore, incomplete information could lead to smaller reconstructed absorption coefficients and total hemoglobin concentrations than those reported here using our 3-D NIR imager. In addition, an investigation with phantoms has shown that NIR alone, in general, reconstructs lower absorption coefficients and therefore lower total hemoglobin concentrations than true values [20
]. This can be seen from two studies of the same data reported in Refs. [7,13
]. Authors in Ref. [7
] reported an average of 35 µmol total hemoglobin concentration of a 2-cm ductal carcinoma in situ
by using NIR measurements alone. After reprocessing the same NIR measurement data using an approximate lesion depth obtained from a separate ultrasound image, the authors reported that the calculated average total hemoglobin concentration was increased to 67 µmol [13
The reported small early-stage invasive cancers appear isolated and are well resolved from background tissues in optical absorption maps as well as in total hemoglobin distributions. However, the combined fibroadenoma and fibrocystic change with scattered foci of lobular neoplasia/lobular carcinoma in situ
case showed no difference in optical absorption and hemoglobin concentration than those obtained from fibroadenoma cases. This suggests that optical tomography may not be sensitive to early-stage mixed benign changes and noninvasive neoplasia/carcinoma in situ
because tumor neovascularization has not been developed. This result is consistent with magnetic resonance imaging (MRI) findings on the low detection sensitivity of carcinoma in situ
]. However, optical imaging may be a valuable tool for monitoring the development or transition of lesions from noninvasive to early invasive stage. Certainly, more cases are needed to validate the observations reported here. For larger cancers, highly heterogeneous wavelength-dependent optical absorption distributions and total hemoglobin distribution have been observed in four cases [18
], and these distributions could provide valuable information for monitoring and assessing cancer therapy under treatment. Currently, we are pursuing research along this line and more cases will be reported in the future.
In principle, the distribution of oxygenation saturation can be estimated as S = oxyHb/(oxyHb+deoxyHb), with deoxyHb and oxyHb distributions calculated from absorption maps at the two wavelengths of 780 and 830 nm. However, because background tissues mainly consist of water and lipid and these two chromophores contribute to the total absorption estimate as well, we could not obtain reasonable background oxygenation saturation and compare it with lesion oxygenation saturation. Recently, we have improved our NIR system by adding another wavelength at 660 nm, which may allow us to accurately estimate the background oxygenation saturation and to compare it with lesion oxygenation saturation.
If we reconstruct the lesion area only, we could distribute partial perturbations caused by background to lesion and increase calculated lesion absorption and therefore hemoglobin concentration. However, with the dual-mesh scheme, we reconstruct the entire imaging volume instead of the lesion area only, and distribute the perturbations to both lesion and background. We did phantom experiments using the dual-mesh scheme and obtained absorption coefficients, which were always within 10% of the true values depending on the phantom contrasts [24
Two-dimensional ultrasound provides fine tissue layer structures in depth (z) direction (, arrow arrays), and the 2-D ultrasound image is coregistered with optical data in z. Therefore, we only need to consider possible angiogenesis extensions in z and we have extended the lesions to the closest normal tissue lines in z. In spatial dimensions, we have some uncertainty in another dimension (y) based on 2-D x–z ultrasound image, and we need to extend the lesion region to a larger area to account for this as well as for possible angiogenesis extension.
The reported optical tomography study was used to image and characterize ultrasonically detected lesions. However, in one benign fibroadenoma case, the lesion was not visible in ultrasound but was seen by conventional X-ray mammogram. By knowing the approximate lesion region with respect to the nipple location from the patient's mammogram, we used a fine mesh for optical reconstruction in a larger region of 9 x 9 x 1.5 cm3, and identified a possible lesion that showed slightly higher optical absorption than that of the background. We believe that optical tomography, assisted by conventional mammography and/or ultrasound localization, has potential as a screening tool to identify and characterize malignancy.
Our initial findings provide evidence that optical tomography, combined with ultrasound, could be used to differentiate early-stage small invasive breast cancers from benign lesions. Because of the limited sample size available, we are not able to provide sensitivity and specificity results in this paper. In addition, for the patients studied, four fibroadenoma cases and one intraductal hyperplasia were excluded from the statistics shown in . The four fibroadenoma cases were scanned at the beginning of the study. One patient was scanned after core biopsy due to scheduling problem, and the possible blood distribution change due to biopsy procedure has to be considered. The other three young patients have small and dense breasts. For these three patients, the optical amplitude and phase data sets were highly scattered even in the normal contralateral breast. Therefore, no reliable background tissue absorption and scattering coefficients can be obtained. Three possible sources for these findings were identified. First, because these breasts were small and dense, the skin and probe contact was not always good. Second, a thick gel layer used for coupling the ultrasound transducer with the skin can serve as a light tunneling medium from sources to detectors. This portion of the light can saturate the detectors and give false readings. Caution was taken in the later studies by compressing the probe harder against the examined breast to ensure good probe-tissue contact, and by placing a very thin gel layer underneath the ultrasound transducer during scanning. The third source are tissue heterogeneities of the young dense breasts. However, by carefully removing outliers from normal breast data, we could obtain reasonably good reference data for imaging. One patient with intraductal hyperplasia data was excluded from the study. This patient had a solid lesion located at the nipple area and the nipple had a very dark color. Four NIR image data sets obtained at the lesion area had the same artifacts and the artifact consistently showed up with very high absorptions at both wavelengths. When the lesion locations were changed in different images with different probe positions, the artifact location changed very little. A similar artifact showed up in the two reference data sets acquired in the contralateral normal breast. We do not know the exact source of this artifact because there was no report that this patient had problems at the contralateral breast. Care was taken in the later studies by acquiring at least four reference data sets at the normal symmetric region of the contralateral breast, as well as at normal regions of the same lesion breast. Reference data sets were always checked for normal background absorption changes before imaging the lesions.