Assessment of Functional Differences in Malignant and Benign Breast Lesions and Improvement of Diagnostic Accuracy by Using US-guided Diffuse Optical Tomography in Conjunction with Conventional US.

Purpose To investigate ultrasonography (US)-guided diffuse optical tomography to distinguish the functional differences of hemoglobin concentrations in a wide range of malignant and benign breast lesions and to improve breast cancer diagnosis in conjunction with conventional US. Materials and Methods The study protocol was approved by the institutional review boards and was HIPAA compliant. Written informed consent was obtained from all patients. Patients (288 women; mean age, 50 years; range, 17-94 years) who underwent US-guided biopsy were imaged with a handheld US and optical probe. The US-imaged lesion was used to guide reconstruction of light absorption maps at four wavelengths, and total hemoglobin (tHb), oxygenated hemoglobin (oxyHb), and deoxygenated hemoglobin (deoxyHb) were computed from the absorption maps. A threshold (80 µmol/L) was chosen on the basis of this study population. Two radiologists retrospectively evaluated US images on the basis of the US Breast Imaging Reporting and Data System lexicon, and a lesion was considered malignant when a score of 4C or 5 was given or a lesion had tHb greater than 80 µmol/L. A two-sample t test was used to calculate significance between groups, and Spearman ρ was computed between hemoglobin parameters and tumor pathologic grades. Results Three tumors were Tis, 37 were T1, 19 were T2-T4 carcinomas, and 233 were benign lesions. The mean maximum tHb, oxyHb, and deoxyHb of Tis-T1 and T2-T4 groups were 89.3 µmol/L ± 20.2 (standard deviation), 65.0 µmol/L ± 20.8, and 33.5 µmol/L ± 11.3, respectively, and 84.7 µmol/L ± 32.8, 57.1 µmol/L ± 19.8, and 34.7 µmol/L ± 18.9, respectively. The corresponding values of benign lesions were 54.1 µmol/L ± 23.5, 38.0 µmol/L ± 17.4, and 25.2 µmol/L ± 13.8, respectively. The mean maximum tHb, oxyHb, and deoxyHb were significantly higher in the malignant groups than the benign group (P <.001, <.001, and .041, respectively). For malignant lesions, the mean maximum tHb moderately correlated with tumor histologic grade and nuclear grade (ρ = 0.283 and 0.315, respectively). The mean maximum oxyHb moderately correlated with tumor nuclear grade (ρ = 0.267). When radiologists' US diagnosis and the tHb were used together, the sensitivity, specificity, positive predictive value, and negative predictive value were 96.6%-100%, 77.3%-83.3%, 52.7%-59.4%, and 99.0%-100%, respectively, for the combined malignant group. Conclusion The tHb and oxyHb correlate with breast cancer pathologic grade and can be used as an adjunct to US to improve sensitivity and negative predictive value in breast cancer diagnosis. (©) RSNA, 2016 Online supplemental material is available for this article.

Breast cancer: assessing response to neoadjuvant chemotherapy by using US-guided near-infrared tomography.

PURPOSE: To assess initial breast tumor hemoglobin (Hb) content before the initiation of neoadjuvant chemotherapy, monitor the Hb changes at the end of each treatment cycle, and correlate these findings with tumor pathologic response. MATERIALS AND METHODS: The HIPAA-compliant study protocol was approved by the institutional review boards of both institutions. Written informed consent was obtained from all patients. Patients who were eligible for neoadjuvant chemotherapy were recruited between December 2007 and May 2011, and their tumor Hb content was assessed by using a near-infrared imager coupled with an ultrasonography (US) system. Thirty-two women (mean age, 48 years; range, 32-82 years) were imaged before treatment, at the end of every treatment cycle, and before definitive surgery. The patients were graded in terms of their final pathologic response on the basis of the Miller-Payne system as nonresponders and partial responders (grades 1-3) and near-complete and complete responders (grades 4 and 5). Tumor vascularity was assessed from total Hb (tHb), oxygenated Hb (oxyHb), and deoxygenated Hb (deoxyHb) concentrations. Tumor vascularity changes during treatment were assessed from percentage tHb normalized to the pretreatment level. A two-sample two-sided t test was used to calculate the P value and to evaluate statistical significance between groups. Bonferroni-Holm correction was applied to obtain the corrected P value for multiple comparisons. RESULTS: There were 20 Miller-Payne grade 1-3 tumors and 14 grade 4 or 5 tumors. Mean maximum pretreatment tHb, oxyHb, and deoxyHb levels were significantly higher in grade 4 and 5 tumors than in grade 1-3 tumors (P = .005, P = .008, and P = .017, respectively). The mean percentage tHb changes were significantly higher in grade 4 or 5 tumors than in grade 1-3 tumors at the end of treatment cycles 1-3 (P = .009 and corrected P = .009, P = .002 and corrected P = .004, and P < .001 and corrected P < .001, respectively). DISCUSSION: These findings indicate that initial tumor Hb content is a strong predictor of final pathologic response. Additionally, the tHb changes during early treatment cycles can further predict final pathologic response.

Early-stage invasive breast cancers: potential role of optical tomography with US localization in assisting diagnosis.

PURPOSE: To investigate the potential role of optical tomography in the near-infrared (NIR) spectrum with ultrasonographic (US) localization as a means of differentiating early-stage cancers from benign lesions of the breast. MATERIALS AND METHODS: The protocol was approved by the institutional review boards and was HIPAA compliant; all participants signed an informed consent. One hundred seventy-eight consecutive women (mean age, 52 years; range, 21-89 years) who underwent US-guided biopsy were imaged with a hand-held probe consisting of a coregistered US transducer and an NIR imager. The lesion location provided by coregistered US was used to guide optical imaging. Light absorption was measured at two optical wavelengths. From this measurement, tumor angiogenesis was assessed on the basis of calculated total hemoglobin concentration (tHb) and was correlated with core biopsy results. For patients diagnosed with carcinomas and followed up with subsequent excision, the tHb was correlated with pathologic parameters. RESULTS: There were two in situ carcinomas (Tis), 35 T1 carcinomas, 24 T2-T4 carcinomas, and 114 benign lesions. The mean maximum and mean average tHb of the Tis-T1 group were 102.0 micromol/L +/- 28.5 (standard deviation) and 71.9 micromol/L +/- 18.8, and those of the T2-T4 group were 100.3 micromol/L +/- 26.4 and 67.0 micromol/L +/- 18.3, respectively. The mean maximum and mean average tHb of the benign group were 55.1 micromol/L +/- 22.7 and 39.1 micromol/L +/- 14.9, respectively. Both mean maximum and mean average tHb levels were significantly higher in the malignant groups than they were in the benign group (P < .001). The sensitivity, specificity, positive predictive value, and negative predictive value for Tis-T1 cancers were 92%, 93%, 81%, and 97%. The corresponding values for T2-T4 tumors were 75%, 93%, 69%, and 95%. CONCLUSION: The angiogenesis (tHb) contrast imaged by using the NIR technique with US holds promise as an adjunct to mammography and US for distinguishing early-stage invasive breast cancers from benign lesions.

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.

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.

Invasive mammary carcinoma after immediate and short-term follow-up for lobular neoplasia on core biopsy.

Lobular neoplasia (LN), including atypical lobular hyperplasia (ALH) and lobular carcinoma in situ, may be encountered in breast core biopsies performed for mammographic abnormalities even though LN is often not, in itself, responsible for the abnormal mammogram. The need for surgical excision following a diagnosis of LN on core biopsy is not well defined. We examined pathologic and mammographic findings in a consecutive series of cases diagnosed as LN to address this issue. Radiology/pathology records were reviewed for cases with a pathology diagnosis of pure LN during the period 1998-2001. Specifically excluded were cases with associated atypical ductal hyperplasia, ductal carcinoma in situ, invasive mammary carcinoma, or any history of breast malignancy. Thirty-five women 39-76 years of age (mean 52 years) were identified. Specimens were obtained as stereotactic core (31) or limited wire-guided biopsy (four). The diagnoses were lobular carcinoma in situ (12), lobular carcinoma in situ/ALH (10), and ALH (13). Fourteen patients did not undergo excisional biopsy and had no subsequent clinical follow-up to warrant additional biopsy (follow-up 6 months to 3 years). Five patients had no immediate excision, but eventually during clinical follow-up for LN (1 month to 3 years), two developed mammographic lesions in the ipsilateral (one patient) or contralateral breast (one patient) that led to diagnoses of invasive mammary carcinoma (lobular and composite ductal-lobular types, 10 and 8 mm, respectively); three patients had subsequent mammographic findings in the ipsilateral or contralateral breast leading to biopsies showing only LN (two patients) or no neoplastic pathology (one patient). The remaining 16 patients (all core biopsied) underwent immediate wire-guided excisions. Thirteen (81%) showed additional foci of LN, one (6.3%) with atypical ductal hyperplasia, and two (12.5%) with invasive lobular carcinoma (3 mm and <1 mm). Three (19%) had no residual disease; however, additional clinical follow-up in one of these patients revealed an invasive mammary carcinoma in the contralateral breast (false-negative mammography). Radiographic findings were calcifications and density/mass lesions in 27 and 8 cases, respectively. Of 27 cases presenting with Ca, 10 showed colocalization of LN and Ca. In the eight cases presenting with density/mass, incidental microscopic microcalcifications colocalized to LN were found in two cases. When present, histologic Ca was associated with LN in 12 of 29 cases studied (41%). Of the 21 patients with immediate or subsequent excision, five (24%) were found to have an associated invasive mammary carcinoma (two on immediate excision and three after short-term follow-up of up to 3 years). The bilaterality of cancer risk was expected; however, the number of invasive carcinomas was not. That the invasive carcinomas detected at follow-up were small implies that they might have been present (but occult) at initial presentation. We conclude that lobular carcinoma in situ detected on core biopsy is potentially a significant marker for concurrent and near-term breast pathology requiring complete intensive multidisciplinary clinical follow-up with specific individualization of patient care.