Normalization of compression-induced hemodynamics in patients responding to neoadjuvant chemotherapy monitored by dynamic tomographic optical breast imaging (DTOBI)

Abstract

Abstract:We characterize novel breast cancer imaging biomarkers for monitoring neoadjuvant chemotherapy (NACT) and predicting outcome. Specifically, we recruited 30 patients for a pilot study in which NACT patients were imaged using dynamic tomographic optical breast imaging (DTOBI) to quantify the hemodynamic changes due to partial mammographic compression. DTOBI scans were obtained pre-treatment (referred to as day 0), as well as 7 and 30 days into therapy on female patients undergoing NACT. We present data for the 13 patients who participated in both day 0 and 7 measurements and had evaluable data, of which 7 also returned for day 30 measurements. We acquired optical images over 2 minutes following 4-8 lbs (18-36 N) of compression. The timecourses of tissue-volume averaged total hemoglobin (HbT), as well as hemoglobin oxygen saturation (SO 2 ) in the tumor vs. surrounding tissues were compared. Outcome prediction metrics based on the differential behavior in tumor vs. normal areas for responders (>50% reduction in maximum diameter) vs. non-responders were analyzed for statistical significance. At baseline, all patients exhibit an initial decrease followed by delayed recovery in HbT, and SO 2 in the tumor area, in contrast to almost immediate recovery in surrounding tissue. At day 7 and 30, this contrast is maintained in non-responders; however, in responders, the contrast in hemodynamic time-courses between tumor and normal tissue starts decreasing at day 7 and substantially disappears at day 30. At day 30 into NACT, responding tumors demonstrate "normalization" of compression induced hemodynamics vs. surrounding normal tissue whereas non-responding tumors did not. This data suggests that DTOBI imaging biomarkers, which are governed by the interplay between tissue biomechanics and oxygen metabolism, may be suitable for guiding NACT by offering early predictions of treatment outcome. Yaffe, and G. J. Czarnota, "Evaluation of neoadjuvant chemotherapy response in women with locally advanced breast cancer using ultrasound elastography," Transl. Oncol. 6(1), 17-24 (2013).

Multimodal breast cancer imaging using coregistered dynamic diffuse optical tomography and digital breast tomosynthesis

“…The slow recovery in HbT as the breast is kept under compression, likely due to the steady decrease in compression force due to tissue relaxation, is consistent with our previous publications. 60,66 However, due to the complexity of the iterative DBT clinical breast positioning procedure, the optical image acquisition did not begin until ∼20 to 30 s after the breast tissue initially experienced compression. As a result, the early response is not captured in the presented data.…”

“…Previously, using a standalone dynamic optical imaging system with a computer controlled compression mechanism, we have seen an early decrease in tumor HbT during compression. 60,66 However, in the example TOBI2 scan, this early decrease has likely occurred before the measurement was initiated (while the radiology technician was positioning the breast under compression to match clinical standards). The significantly larger decrease in tumor HbT observed after the transition to full compression versus the surrounding normal tissue (likely related to the higher stiffness of tumor tissue) may be a useful tumor marker and will be further characterized in future work.…”

Diffuse optical spectroscopic imaging reveals distinct early breast tumor hemodynamic responses to metronomic and maximum tolerated dose regimens

“…DOSI measures absolute concentrations of oxyhemoglobin, deoxyhemoglobin, lipid, and water. These parameters have been shown by multiple research groups to be valuable prognostic markers at various points throughout NAC [6,9,16,21,27,45,46,48,49,50,53]. For example, a recent landmark multicenter study (ACRIN 6691) showed that changes in tumor deoxyhemoglobin, water, and lipid at midpoint of NAC correlated strongly to pCR [48].…”

Longitudinal optical monitoring of blood flow in breast tumors during neoadjuvant chemotherapy

“…These reconstructed quantities have been shown to discriminate between malignant and healthy tissue in the breast (Srinivasan et al 2005, Spinelli et al 2005, Cerussi et al 2006, Choe et al 2009, Wang et al 2010, Fang et al 2011, Mastanduno et al 2014). Importantly, several studies have employed DOSI techniques to investigate functional changes in malignant tissue over the course of NAC and have correlated these changes with the patients’ responses to treatment (Choe et al 2005, Tromberg et al 2005, Zhou et al 2007, Cerussi et al 2007, Zhu et al 2008, Jiang et al 2009, Soliman et al 2010, Cerussi et al 2011, Roblyer et al 2011, Falou et al 2012, Ueda et al 2012, Choe and Durduran 2012, Busch et al 2013a, Tromberg et al 2016, Sajjadi et al 2017). The present paper is focused on another diffuse optical technique, diffuse correlation spectroscopy (DCS), which utilizes the temporal fluctuations of detected light intensity to probe microvasculature blood flow in deep tissue (Durduran et al 2010).…”