Tumor Angiogenesis Change Estimated by Using Diffuse Optical Spectroscopic Tomography: Demonstrated Correlation in Women Undergoing Neoadjuvant Chemotherapy for Invasive Breast Cancer?

Abstract

Purpose:To investigate if changes in tumor angiogenesis associated with complete pathologic response (pCR) or partial pathologic response (pPR) to treatment can be demonstrated by using diffuse optical spectroscopic (DOS) tomography. Materials and Methods:All participants in this prospective, HIPAA-compliant, institutional review board-approved study provided written informed consent. Eleven women with invasive breast carcinoma were imaged with DOS tomography prior to, during, and at completion of neoadjuvant chemotherapeutic regimens. By using region of interest (ROI) analysis, the DOS measure of total tissue hemoglobin (Hb T ) was temporally correlated with quantitative measures of existing (CD31-expressing) and tumor-induced (CD105-expressing) vessels, in pretreatment and posttreatment tissue specimens, to assess change. Results:Quantifi ed angiogenesis alone in pretreatment core biopsy specimens did not predict treatment response, but mean vessel density (MVD) and mean vessel area (MVA) of CD105-expressing vessels were signifi cantly decreased in women with pCR ( n = 7) ( P , .001 and P = .003, respectively). MVA of CD105-expressing vessels was also signifi cantly reduced at comparison of pre-and posttreatment residual tumor for women with pPR ( n = 4) ( P = .033). A longitudinal analysis showed signifi cant decreases ( P = .001) in mean Hb T levels during neoadjuvant chemotherapy in breast abnormality ROIs for women with pCR but not women with pPR. For women with pCR, but not women with pPR, pretreatment MVD of CD105-expressing vessels correlated with pretreatment Hb T ( P Յ .001). Conclusion:DOS tomographic examinations in women with breast cancer who are receiving neoadjuvant chemotherapy show a mean decrease in Hb T with time in patients with pCR only. Observed pretreatment and posttreatment correlates with quantifi ed angiogenesis markers confi rm the likely biologic origin for this DOS signature and support its potential to predict angiogenic tissue response early in the treatment cycle.q RSNA, 2011Supplemental material : http://radiology.rsna.org/lookup /suppl

Predicting Breast Tumor Response to Neoadjuvant Chemotherapy with Diffuse Optical Spectroscopic Tomography prior to Treatment

“…While this hypothesis was not studied explicitly, the apparently prognostic indication provided by Pre-TxHb T when combined with earlier pathological analysis (17) is consistent with the theory. Specifically, our earlier study of DOST versus pathologic immunohistochemical staining of biopsy specimens and resected surgical tissues in the same breasts showed that Hb T changes were directly correlated to changes in pathologically measured CD31 reduction in response to NAC (17). Here, CD31 is a pan-endothelial marker for identifying pre-existing blood vessel density and size.…”

“…After all treatment cycles were completed, DOST images of both breasts were obtained several days before surgery. Histopathological characteristics of the resected tissue were evaluated after surgery (17), and a complete (pCR) or incomplete (pIR) pathological response to NAC was determined and compared with the DOST results.…”

Monitoring the response to neoadjuvant hormone therapy for locally advanced breast cancer using three-dimensional time-resolved optical mammography

“…This dip in [HbT] (and in absorption at both wavelengths) followed by an increase suggests that optically measured early changes in the tumor region following treatment may not always correlate with final outcome, as has been shown in patients treated with chemotherapy. 40,41 An area of artifact was also seen in this image, and care was taken not to include this region in the image analysis, to avoid introducing errors to the calculated values.…”

Integration of microwave tomography with magnetic resonance for improved breast imaging

“…The most robust and diagnostically significant NIRST parameter has been total hemoglobin concentration, Hb T , evidently because it is a surrogate for localized vascular density and associated angiogenic activity in cancers. 19,55 In prior studies, 29 MT conductivity has been highly correlated with NIRST Hb T in the breasts of women examined with both modalities, and hence, the addition of MR spatial information should similarly strengthen the diagnostic accuracy of MT. Further, MT offers some potential advantages over NIRST-namely, its noncontacting imaging array (eliminating poor/inconsistent sensor contact effects, albeit a coupling fluid is involved), and its much higher frequency signal amplitude and phase for image reconstruction (NIRST light is amplitude-modulated around 100 MHz to generate the detected signal amplitude and phase response) with much less signal attenuation (NIRST attenuation is also dependent on the source wavelengths of light).…”