Noninvasive Monitoring of Breast Cancer during Neoadjuvant Chemotherapy Using Optical Tomography with Ultrasound Localization

Abstract

The purposes of this study were 1) to investigate the feasibility of using optical tomography in the near-infrared (NIR) spectrum combined with ultrasound (US) localization (NIR/US) in monitoring tumor vascular changes and assessing tumor pathological response during chemotherapy and 2) to compare the accuracy of NIR/US with magnetic resonance imaging (MRI) in predicting residual cancer after neoadjuvant chemotherapy. Eleven female patients were studied during treatments with a combined imager consisting of a commercially available US system coupled to an NIR imager. Contrast-enhanced MRI was performed before treatment and surgery. Tumor vascular content was assessed based on total hemoglobin concentration and volume obtained from NIR data. A percentage blood volume index (%BVI) was calculated as the percentage ratio of the product of total hemoglobin concentration and volume normalized to pretreatment values. At treatment completion, pathologic assessment revealed three response groups: complete or near-complete responders (A), partial responders (B), and nonresponders (C). The mean %BVIs of groups A, B, and C at the treatment completion were 29.1 +/- 6.9%, 46.3 +/- 3.7%, and 86.8 +/- 30.1%, respectively (differences statistically significant, P < .04). At the end of cycle 2, the %BVI of group A was noticeably lower than that of the partial (P = .091) and nonresponder groups (P = .075). Both NIR/US and MRI were equally effective in distinguishing different response groups in this pilot study. Our initial findings indicate that NIR/US using %BVI can be used during chemotherapy to repeatedly monitor tumor vascular changes. NIR/US also may evaluate pathologic response during treatment allowing for tailoring therapies to response.

Diffuse optical spectroscopic imaging correlates with final pathological response in breast cancer neoadjuvant chemotherapy

“…An important practical advantage of our DOSI approach is that it can be used frequently in unconventional settings such as a doctor's surgery or clinic. Portable optical imaging platforms can easily supplement existing radiological methods either as standalone devices or as units integrated into established technologies such as ultrasound, mammography or MRI [40,53].…”

“…DOS-measured tumour concentrations of deoxyhaemoglobin (ctHHb), oxyhaemoglobin (ctO 2 Hb) and ctH 2 O dropped 27 ± 15, 33 ± 7 and 11 ± 15 per cent, respectively, within one week of the first treatment for pathology-confirmed responders (N = 6), while non-responders (N = 5) and normal side controls showed no significant changes in these parameters. Later studies have subsequently reported correlations between sensitive NIR parameters and pathological response [39][40][41].…”

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

“…DOS tomography measures bulk, or large volume, total tissue hemoglobin aging biologic markers that refl ect tissue function and hence should better predict response to therapy. Diffuse optical spectroscopic (DOS) tomography provides information about the intrinsic vascular and ultrastructural biophysical composition of breast tissue (9)(10)(11)(12)(13)(14)(15)(16)(17). The validation of DOS tomographic images and spectra requires both morphologic diagnoses from histopathologic examination and parametric analysis of tissue features, beyond the declared pathologic diagnosis ( 18 ).…”

“…Monitoring of breast cancer treatment response to neoadjuvant chemotherapy with diffuse optical spectroscopy ( 9 ) or tomography ( 11,12,32,45 ) has demonstrated encouraging initial results in single-trial studies. Zhu and colleagues ( 11 ), who evaluated vessel density changes in 16 subjects in response to neoadjuvant chemotherapy while monitoring them with near-infrared imaging, observed a moderately signifi cant ( P = .056) correlation between the quantitative MVD measures of existing vessels (CD31-positive vessels) in residual tumor specimens and Hb T level, but no statistical significance was found between responder and nonresponder groups.…”

Accuracy of unidimensional and volumetric ultrasound measurements in predicting good pathological response to neoadjuvant chemotherapy in breast cancer patients

“…Chapgar et al [10] noted that, in 189 patients treated with NAC at the MD Anderson Cancer Center (Houston, TX), the correlation of physical examination, mammography and US with pathological tumour size was weak to moderate with correlation coefficients of 0.42, 0.41 and 0.42 respectively. Small case series however, have reported much higher accuracy of US in predicting pCR [11,12] and there is increasing interest in employing advanced ultrasound-based technologies, for example assessing vascularity, to further improve performance [13,14].…”