Molly Lara Flexman

Augmented reality for radiation dose awareness in the catheterization lab

There is a growing awareness of the effects of radiation exposure to the patient and staff during minimally-invasive x-ray guided interventions. Augmented reality can provide real-time visualization of radiation dose during the procedure with relevant information displayed in the appropriate context.

Abstract P5-01-05: Early optical tomography changes correlate with residual cancer burden scores in women receiving neoadjuvant chemotherapy

Background: The Residual Cancer Burden (RCB) score predicts survival in patients (pts) with breast cancer (BC) treated with neoadjuvant chemotherapy (NACT). Predicting tumor response early during NACT may allow for treatment optimization. Diffuse optical tomography (DOT) is an imaging modality that measures the distribution of water (H2O), oxy- (HbO), and deoxy-hemoglobin (Hb) concentrations as a surrogate for vascularity and architecture. We hypothesize that the 2-week change in DOT parameters will correlate with the RCB score. We also explored the association between DOT parameters and tissue biomarkers: Ki-67 change and microvessel density (MVD). Methods: Women with stage II-IIIc invasive BC scheduled to receive NACT with 12 cycles of a weekly taxane followed by 4 cycles of doxorubicin with cyclophosphamide were enrolled. Treatment with biologic therapies was allowed. DOT assessments were made before NACT and after 2 weeks on treatment. DOT data were reconstructed into 3D images of the tumor region, from which HbO, Hb, and H2O concentrations were extracted. Final pathology specimens were scored for the RCB index (continuous), RCB class (0, 1, 2, 3), and a dichotomized RCB score (RCB class 0 or 1: responders; RCB class 2 or 3: non-responders). Ki-67 was measured on baseline tumor biopsies and surgical specimens. MVD was assessed on baseline tumor biopsies. Correlation analysis, ANOVA testing, and two sample t-tests were used to evaluate the relationship between the 2-week changes in DOT parameters and the RCB score and Ki-67 change. Correlation was assessed between MVD and baseline DOT measures. Results: Since July 2011, we have recruited 28 pts of a total planned accrual of 40. 25 pts have had surgery and complete data are available for 23. Of the 23 pts, 6 had a pCR (RCB 0), 2 had RCB 1, 10 had RCB 2, and 5 had RCB 3. The Pearson correlations (r) between the 2-week change in HbO, Hb, and H2O with the continuous RCB index were 0.65 (p=0.002), 0.70 (p=0.0006), and 0.70 (p=0.0006), respectively. There was a significant difference in the 2-week Hb change for pts with RCB 0 compared to pts with RCB 1, 2, or 3. There were significant differences in the 2-week change in H2O and HbO for pts with RCB 0 compared to pts with RCB 2. There were also significant differences between DOT parameters by the dichotomized RCB score (Table 1). There was an association in Ki-67 change and 2-week H2O change (r=0.43 p=0.059). A subset of 15 pts had MVD assessments, but these did not correlate with baseline DOT parameters (r ≤0.18, p>0.5). Conclusions: Two-week DOT change is an early predictor of response to NACT as measured by the RCB score. We found significant associations between the RCB index with 2-week changes in HbO, Hb, and H2O. Significantly different changes in DOT parameters were associated with the other RCB classifications. Ki-67 changes and baseline MVD were not statistically significantly associated with DOT parameters. We are analyzing static and dynamic DOT data on the remaining pts. Additional pts are being recruited to evaluate DOT9s predictive ability by tumor subtype. Citation Format: Emerson A Lim, Jacqueline E Gunther, Molly Flexman, Hyun K Kim, Hanina Hibshoosh, Kevin Kalinsky, Katherine Crew, Matthew Maurer, Sheldon Feldman, Bret Taback, Preya Ananthakrishnan, Margaret Chen, Susan Refice, Andreas Hielscher, Dawn L Hershman. Early optical tomography changes correlate with residual cancer burden scores in women receiving neoadjuvant chemotherapy [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P5-01-05.

P2-10-09: Detecting Breast Cancer with Dynamic Diffuse Optical Tomographic Imaging.

Background: Over the last decade diffuse optical tomography (DOT) has emerged as a novel medical imaging modality. Near-infrared light is used to non-invasively probe biological tissue, and three-dimensional (3D) maps of blood-dependent parameters can be obtained. Several studies are underway to show the clinical utility of DOT for imaging brain disease, joint disease, and breast cancer. Here we present the largest clinical study to date that uses hemodynamic effects caused by a simple breath hold to identify breast tumors using DOT. Methods: We have designed and built a DOT breast imaging system that can acquire full 3D data sets within a fraction of a second. The system affords the ability to study fast hemodynamic effects in both breasts simultaneously. Using non-compressive imaging heads we measured the oxygenated and deoxygenated hemoglobin levels in the breasts of 15 patients whose mammogram showed a mass >1 cm (4 benign, 11 malignant) and 3 healthy controls. Data was acquired over the course of a 30-second breath hold and 30 seconds thereafter. In addition, a baseline measurement of 30 seconds prior to the breath hold was obtained. A multi-wavelength image reconstruction algorithm was used to create 3D maps of hemoglobin-dependent parameters (Δ[HbO2] and Δ[Hb]) in the breast every 0.58 seconds, over the course of the 90-second experiment. An image analysis algorithm identified regions of peak percentage change in [Hb] and [HbO 2 ] in the breast and then computed the average hemoglobin levels in those regions. Results: We observed an increase in the hemoglobin levels in all breasts during the breath hold. Upon resuming breathing, these hemoglobin levels returned to baseline. Tumor bearing breasts showed a statistically significant slower return to baseline than healthy breasts. In particular, we found that tumors can be detected by a substantially larger Δ[Hb] value as compared to normal tissue in images acquired 15 seconds following the end of the breath hold. In 10 of 11 patients the malignant tumor was identified using this technique, suggesting sensitivity over 90%. No regions of increased Δ[Hb] were seen in the healthy breasts, or in the breasts with benign masses. The peak percentage change in [Hb] at the 15 second post-breath hold time point was 10.0 ± 6.0% (n=11) in the malignant tumors compared to 1.4 ± 0.5% (n=3) (p=0.001) in healthy patients and 4.8 ± 1.9% in benign masses (n=4)(p=0.03). Discussion: A breath hold impedes venous return to the heart, which causes pooling of blood in the breast. This is observed as an increase in [Hb] and [HbO2] using DOT. Tumor vasculature is known to be more disorganized, tortuous, and leakier than normal vasculature. Therefore, once the breath hold is released and blood is allowed to drain from the breast, blood accumulated in the tumor during the breath hold will drain more slowly than blood in healthy tissue. This study has shown that DOT allows us to visualize these hemodynamic effects and use them to detect tumors with a simple breath hold and compression-free imaging head. Future studies need to explore the detection limits and general clinical utility of this technique for screening, differentiating malignant from benign masses, and treatment monitoring. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-10-09.