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Near-infrared Laser Computed Tomography of the Breast

Rationale and Objectives

The purpose of the present study was to evaluate a near-infrared (NIR) laser breast imaging system (Computed Tomography Laser Mammography [CTLM]) as an adjunct to mammography by means of receiver-operating characteristic (ROC) analysis. The NIR technique used in this study is based on the absorption of NIR light by hemoglobin. Malignant tumors can be detected by imaging their neovascularization.

Materials and Methods

Eighty-two patients were examined by both CTLM and mammography. Seventy-nine of the 82 patients underwent biopsies, and three patients had 2-year follow up. Three-dimensional scans were acquired with an NIR laser computed tomographic scanner (the CTLM system) at a slice thickness of 4 mm. Mammograms were analyzed alone and together with CTLM images.

Results

Histology revealed 37 benign and 42 malignant lesions. For the combination of mammography and CTLM, the area under the ROC curve was significantly larger than for mammography alone. In addition, it was shown that the difference in area under the ROC curve between the combination of both methods and mammography alone was considerably larger for dense breasts than for radiolucent breasts, although these differences were not statistically significant.

Conclusion

CTLM, used as an adjunct, may serve as a feasible tool to improve the diagnostic capabilities of mammography.

Breast cancer is the most frequent malignancy in women worldwide ( ). Statistically, in the United States, one in seven women will develop breast cancer during her lifetime ( ). Diagnostic mammography has been shown to have an average sensitivity for the detection of cancer of 75%, and 60 to 80 of every 100 biopsies are negative for cancer. In specific cases, magnetic resonance imaging (MRI) can solve some of these problems, increasing sensitivity to about 95%, but with a presently significantly lower specificity than mammography ( ). In addition, MRI examinations are still very expensive. For these reasons, a different approach to breast imaging is desirable.

In theory, optical methods based on near-infrared (NIR) imaging have high potential to become valuable diagnostic tools in breast imaging ( ). There are several reasons for this. First, the breast is fully accessible for imaging with optical methods because of its surface location, relatively small size, and absence of bony structures. Second, at 800 nm, it is possible to exploit the difference in absorption between total hemoglobin and water or fat as an intrinsic contrast. Hemoglobin will then act as a natural contrast medium, and computed laser tomography of the breast will therefore produce a “hemoglobin angiogram,” revealing the normal vascular structures of the breast. In addition, because all tumors require new blood vessels to survive and grow (neoangiogenesis), NIR tomographic imaging can detect tumors within the breast. Third, no ionizing radiation is needed, and the majority of optical systems work without compression, factors that increase its acceptance by patients. Finally, the method is rather inexpensive and easily deployed.

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Materials and methods

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Technique

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Figure 1, Gantry of the Computed Tomography Laser Mammography system using a third-generation computed tomography design. There is an array of 84 collimated photodiodes and a near-infrared laser operating at 808 nm.

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Figure 2, Medical optical spectral window demonstrated by the absorption spectra of the major chromophores in skin ( 20 21 ). The absorption factor is equivalent to the optical absorption coefficient, μ a . OxyHb, oxyhemoglobin; DeoxyHb, deoxyhemoglobin. (From Chance ( 21 ), with permission).

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Patients

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Table 1

Seventy-nine of 82 Patients Included in This Study Had Biopsies on the Basis of Findings on Mammography, Ultrasound, Magnetic Resonance Imaging, Physical Examination, or a Combination of These Methods; Three Patients with Benign Findings Were Included on the Basis of 2-Year Follow-up

Basis for Biopsy Number of Patients Mammography 47 Ultrasound 5 Mammography and ultrasound 7 Physical examination and mammography 10 MRI 5 Physical examination and ultrasound 2 Physical examination and MRI 2 Mammography and MRI 1

MRI, magnetic resonance imaging.

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Analysis

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Reading Mammograms and CTLM Studies

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Statistical Analysis

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Results

Histology

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Table 2

Histologic Findings in the 79 Patients Who Were Biopsied; There Were 42 Malignant Cases in Total

Finding Number of Lesions Size (mm), Mean ± SD Malignant findings 16.7 ± 14.1 Invasive ductal carcinoma 29 Invasive lobular carcinoma 4 19.3 ± 7.0 Mucinous carcinoma 1 10 High-grade DCIS 6 22.4 ± 23.9 Low-grade DCIS 2 36.5 ± 47.4 Benign findings Fibrocystic changes 12 Fibrosis 9 Fibroadenoma 7 17.0 ± 11.0 Benign calcifications 3 Papilloma 2 Atypical ductal hyperplasia 2 Hamartoma 1 Chronic mastitis 1 Follow-up 3

DCIS, ductal carcinoma in situ; SD, standard deviation.

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Mammography

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Statistical Analysis

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Figure 3, Receiver-operating characteristic (ROC) curve analysis between mammography and Computed Tomography Laser Mammography (CTLM) plus mammography. The bivariate χ 2 statistic of the difference between the two ROC estimates was statistically significant, with a corresponding P value of .033. ACR, American College of Radiology.

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Figure 4, For radiographically dense breasts, the difference between the area under the receiver-operating characteristic curve was even greater. However, mainly because of the smaller number of patients in this subset, the difference did not reach statistical significance (χ 2 test, P = .073). ACR, American College of Radiology; CTLM, Computed Tomography Laser Mammography.

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Figure 5, The difference in the area under the receiver-operating characteristic curve between mammography and the combination of Computed Tomography Laser Mammography (CTLM) and mammography was not statistically significant for radiolucent breasts (American College of Radiology [ACR] Breast Imaging Reporting and Data System density 1 or 2).

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Cases

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Case 1: Ductal Carcinoma in Situ and Invasive Ductal Carcinoma

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Figure 6, Correlation between mammography, Computed Tomography Laser Mammography, and magnetic resonance imaging in a 28-year-old woman with an invasive ductal carcinoma and ductal carcinoma in situ (high grade) in her left breast.

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Case 2: Invasive Ductal Carcinoma

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Figure 7, Correlation between mammography and Computed Tomography Laser Mammography (CTLM) showing an invasive ductal carcinoma. On mammography, a architectural distortion at 12 o'clock was present. The CTLM images show a hyperintensity (white arrows) indicating hypervascularity.

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Case 3: Cystosarcoma Phyllodes and Fibroadenoma

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Figure 8, Comparison of near-infrared mammography (Computer Tomography Laser Mammography [CTLM], three-dimensional surface rendering) (left) , magnetic resonance imaging (MRI; T 2 -weighted) (center) , and the operation specimen (right) . Both CTLM and MRI showed the larger mass that was located medially (M). The smaller mass, located laterally (L), was seen only on MRI and did not appear on near-infrared mammography. Histologic examination revealed a malignant phyllodes tumor as the larger mass and a fibroadenoma as the smaller mass. The structures at the base of the breast in the near-infrared image are probably caused by large vessels and dense glandular tissue.

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Figure 9, (a) Fibroadenoma with proliferation of stromal cells around ducts (25 ×, hematoxylin and eosin). (b) Immunohistochemical staining showing moderate intratumoral vascularization by cluster of differentiation 31 (CD31) (200 ×, alkaline phosphatase antialkaline phosphatase). (c) Malignant phyllodes tumor with dense spindle-cell stroma (25 ×, hematoxylin and eosin). (d) Immunohistochemical staining demonstrating dense intratumoral vascularization by CD31 (200 ×, alkaline phosphatase antialkaline phosphatase).

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Discussion

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Study Limitations

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Conclusion

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