Jacqueline Gunther

Optical biomarkers for breast cancer derived from dynamic diffuse optical tomography

Abstract. Diffuse optical tomography (DOT) is a noninvasive, nonionizing imaging modality that uses near-infrared light to visualize optically relevant chromophores. A recently developed dynamic DOT imaging system enables the study of hemodynamic effects in the breast during a breath-hold. Dynamic DOT imaging was performed in a total of 21 subjects (age 54±10  years) including 3 healthy subjects and 18 subjects with benign (n=8) and malignant (n=14) masses. Three-dimensional time-series images of the percentage change in oxygenated and deoxygenated hemoglobin concentrations ([HbO2] and [Hb]) from baseline are obtained over the course of a breath-hold. At a time point of 15 s following the end of the breath-hold, [Hb] in healthy breasts has returned to near-baseline values (1.6%±0.5%), while tumor-bearing breasts have increased levels of [Hb] (6.8%±3.6%, p<0.01). Further, healthy subjects have a higher correlation between the breasts over the course of the breath-hold as compared with the subjects with breast cancer (healthy: 0.96±0.02; benign: 0.89±0.02; malignant: 0.78±0.23, p<0.05). Therefore this study shows that dynamic features extracted from DOT measurements can differentiate healthy and diseased breast tissues. These features provide a physiologic method for identifying breast cancer without the need for ionizing radiation.

Combined dynamic and static optical tomography for prediction of treatment outcome in breast cancer patients

We explored evidence that a combination of dynamic and static diffuse optical tomography can be used to predict treatment response in patients undergoing neo adjuvant chemotherapy. Both blood chromophore concentrations and hemodynamic signatures were measured over the 5-month course of treatment.

Dynamic Diffuse Optical Tomography for Monitoring Neoadjuvant Chemotherapy in Patients with Breast Cancer

Purpose To identify dynamic optical imaging features that associate with the degree of pathologic response in patients with breast cancer during neoadjuvant chemotherapy (NAC). Materials and Methods Of 40 patients with breast cancer who participated in a longitudinal study between June 2011 and March 2016, 34 completed the study. There were 13 patients who obtained a pathologic complete response (pCR) and 21 patients who did not obtain a pCR. Imaging data from six subjects were excluded from the study because either the patients dropped out of the study before it was finished or there was an instrumentation malfunction. Two weeks into the treatment regimen, three-dimensional images of both breasts during a breath hold were acquired by using dynamic diffuse optical tomography. Features from the breath-hold traces were used to distinguish between response groups. Receiver operating characteristic (ROC) curves and sensitivity analysis were used to determine the degree of association with 5-month treatment outcome. Results An ROC curve analysis showed that this method could identify patients with a pCR with a positive predictive value of 70.6% (12 of 17), a negative predictive value of 94.1% (16 of 17), a sensitivity of 92.3% (12 of 13), a specificity of 76.2% (16 of 21), and an area under the ROC curve of 0.85. Conclusion Several dynamic optical imaging features obtained within 2 weeks of NAC initiation were identified that showed statistically significant differences between patients with pCR and patients without pCR as determined 5 months after treatment initiation. If confirmed in a larger cohort prospective study, these dynamic imaging features may be used to predict treatment outcome as early as 2 weeks after treatment initiation.

Using diffuse optical tomograpy to monitor tumor response to neoadjuvant chemotherapy in breast cancer patients

Breast cancer patients often undergo neoadjuvant chemotherapy to reduce the size of the tumor before surgery. Tumors which demonstrate a pathologic complete response associate with improved disease-free survival; however, as low as 10% of patients may achieve this status. The goal is to predict response to anti-cancer therapy early, so as to develop personalized treatments and optimize the patient’s results. Previous studies have shown that tumor response can be predicted within a few days of treatment initiation. We have developed a diffuse optical tomography (DOT) imaging system for monitoring the response of breast cancer patients to neoadjuvant chemotherapy. Our breast imaging system is a continuous wave system that uses four wavelengths in the near-infrared spectrum (765 nm, 808 nm, 827 nm, and 905 nm). Both breasts are imaged simultaneously with a total of 64 sources and 128 detectors. Three dimensional reconstructions for oxy-hemoglobin concentration ([HbO2]), deoxy-hemoglobin ([Hb]) concentrations, and water are performed using a PDE-constrained multispectral imaging method that uses the diffusion approximation as a model for light propagation. Each patient receives twelve weekly treatments of Taxane followed by four cycles of Doxorubicin and Cyclophosphamide (AC) given every other week. There are six DOT imaging time points: baseline, week 3 and 5 of Paclitaxel, before cycle 1 and 2 of AC, and before surgery. Preliminary results show that there is statistical significance for the percent change of [HbO2], [Hb], [HbT], and percent water at week 2 from the baseline between patients with a pathologic response to chemotherapy.

Predicting tumor response in breast cancer patients using diffuse optical tomography

We have developed a diffuse optical tomography imaging system to track breast tumor progression in patients undergoing neoadjuvant chemotherapy. Preliminary results have shown that tumor response can be predicted by the second week of treatment.

Diffuse Optical Tomography Imaging System for Monitoring Breast Tumor Response to Neoadjuvant Chemotherapy

We developed a diffuse optical tomography (DOT) system that can be used to perform longitudinal studies of breast tumors during neoadjuvant chemotherapy. Preliminary results demonstrate that DOT can image early tumor vascular response to treatment.

Chemotherapy Monitoring of Breast Cancer Patients with a Dual-Breast Dynamic Optical Tomography System

In a clinical pilot study we explored evidence that dynamic diffuse optical tomography can be used to predict treatment response in patients undergoing neoadjuvant chemotherapy.

A Dynamic Image Reconstruction Method with Spatio-Temporal Constraints

We introduce here a temporally constrained image reconstruction algorithm for fast dynamic imaging of the spatial distribution of tissue parameters such as oxy-hemoglobin, HbO2, or deoxy-hemoglobin, Hb, and their derived parameters, e.g., HbT or StO2. An unknown spatial-temporal distribution of the tissue parameter is represented by a combination of basis functions where bases are predefined and their coefficients are unknown. The performance of the new algorithm is evaluated using experimental studies with dynamic imaging of vascular disease in foot. The results show that the temporally constrained algorithm leads to 26- fold acceleration in the image reconstruction as compared to more traditional methods that have to reconstruct all time frames data sequentially.

Baseline oxygen saturation comparison between pathologic complete responders and extensive residual cancer cases in response to neoadjuvant chemotherapy

In this retrospective cohort study, we examine the hypothesis that baseline oxygen saturation (SO2%) in contralateral normal tissue can be a quantitative measurement for predicting tumor response to neoadjuvant chemotherapy (NAC). Using our dynamic custom-built dual breast dynamic diffuse optical tomography (DOT) imager, we reconstructed SO2% measurement concentration for 12 stage II or III breast cancer patients. Six patients achieved pCR (RCB-0) and the other half had extensive residual disease (RCB-III). Baseline SO2% in contralateral normal tissue was statistically significantly higher in RCB-III subjects than in pCR (p = 0.025). From ROC analyses, baseline SO2% in contralateral normal breast tissue was able to discriminate pCR from RCB-III patients (AUC 0.889) with sensitivity and specificity of 83%.

5-Month Monitoring of Tumor Response in Patients with Breast Cancer who undergo Neoadjuvent Therapy with Diffuse Optical Tomography

In a clinical pilot study involving patients undergoing neoadjuvant chemotherapy, we explored evidence that diffuse optical tomography can be used to monitor tumor progression and predict treatment response.