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.
Infantile hemangiomas (IH) are common vascular growths that occur in 5-10% of neonates and have the potential to cause disfiguring and even life-threatening complications. Currently, no objective tool exist to monitor either progression or treatment of IH. To address this unmet clinical need, we have developed a handheld wireless device (HWD) that uses diffuse optical spectroscopy for the assessment of IH. The system employs 4 wavelengths (l=780nm, 805nm, 850nm, and 905nm) and 6 source-detector pairs with distances between 0.6 and 20 mm. Placed on the skin surface, backreflection data is obtained and a multispectral evolution algorithm is used to determine total hemoglobin concentration and tissue oxygen saturation. First results of an ongoing pilot study involving 13 patients (average enrollment age = 25 months) suggest that an increase in hypoxic stress over time can lead to the proliferation of IH. Involuting IH lesions showed an increase in tissue oxygen saturation as well as a decrease in total hemoglobin.
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 ([HbO 2 ] 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.
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.
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.
Infantile hemangiomas (IH) are common vascular growths that occur in 5-10% of neonates and have the potential to cause disfiguring and even life-threatening complications. With no objective tool to monitor IH, a handheld wireless device (HWD) that uses diffuse optical spectroscopy has been developed for use in assessment of IH by measurements in absolute oxygenated and deoxygenated hemoglobin concentration as well as scattering in tissue. Reconstructions of these variables can be computed using a multispectral evolution algorithm. We validated the new system by experimental studies using phantom experiments and a clinical study is under way to assess the utility of DOI for IH.
Although anti-angiogenic agents have shown promise as cancer therapeutics, their efficacy varies between tumor types and individual patients. Providing patient-specific metrics through rapid noninvasive imaging can help tailor drug treatment by optimizing dosages, timing of drug cycles, and duration of therapy-thereby reducing toxicity and cost and improving patient outcome. Diffuse optical tomography (DOT) is a noninvasive three-dimensional imaging modality that has been shown to capture physiologic changes in tumors through visualization of oxygenated, deoxygenated, and total hemoglobin concentrations, using non-ionizing radiation with near-infrared light. We employed a small animal model to ascertain if tumor response to bevacizumab (BV), an anti-angiogenic agent that targets vascular endothelial growth factor (VEGF), could be detected at early time points using DOT. We detected a significant decrease in total hemoglobin levels as soon as one day after BV treatment in responder xenograft tumors (SK-NEP-1), but not in SK-NEP-1 control tumors or in non-responder control or BV-treated NGP tumors. These results are confirmed by magnetic resonance imaging T2 relaxometry and lectin perfusion studies. Noninvasive DOT imaging may allow for earlier and more effective control of anti-angiogenic therapy.
KEYWORDS: Digital signal processing, Breast, Imaging systems, Sensors, Tumors, Breast imaging, Signal detection, Optical tomography, Dynamical systems, Tissues
Diffuse optical tomography has shown promising results as a tool for breast cancer screening and monitoring response to chemotherapy. Dynamic imaging of the transient response of the breast to an external stimulus, such as pressure or a respiratory maneuver, can provide additional information that can be used to detect tumors. We present a new digital continuous-wave optical tomography system designed to simultaneously image both breasts at fast frame rates and with a large number of sources and detectors. The system uses a master-slave digital signal processor-based detection architecture to achieve a dynamic range of 160 dB and a frame rate of 1.7 Hz with 32 sources, 64 detectors, and 4 wavelengths per breast. Included is a preliminary study of one healthy patient and two breast cancer patients showing the ability to identify an invasive carcinoma based on the hemodynamic response to a breath hold.
We introduce here a transport-theory-based PDE-constrained multispectral imaging algorithm for direct reconstruction
of the spatial distribution of chromophores in tissue. The method solves the forward and inverse problems
simultaneously in the framework of a reduced Hessian sequential quadratic programming method. The performance of
the new algorithm is evaluated using numerical and experimental studies involving tumor bearing mice. The results
show that the PDE-constrained multispectral method leads to 15-fold acceleration in the image reconstruction of tissue
chromophores when compared to the unconstrained multispectral approach and also gives more accurate results when
compared to the traditional two-step method.
KEYWORDS: Breast, Digital signal processing, Imaging systems, Tumors, Breast cancer, Optical imaging, Mammography, Breast imaging, Signal processing, Sensors
Continuous wave optical tomography is non-ionizing, uses endogenous contrast, and can be performed quickly and at
low cost which makes it a suitable imaging modality for breast cancer screening. Using multiple wavelengths of light to
illuminate the breast at various angles, three-dimensional images of the distribution of chromophores such as oxy- and
deoxy-hemoglobin can help identify cancerous tissue. Dynamic optical imaging can provide additional insight into
cancer characteristics such as angiogenesis and metabolism. Here we present the first clinical data acquired with our
novel digital breast imaging system. This system is based upon a Digital Signal Processor (DSP) architecture that
leverages the immediate digitization of acquired analog data to reduce noise and quickly process large amounts of data.
Employing this new instrument we have investigated the dynamic changes due to a breath hold and its potential for use
in breast cancer screening. Over the course of a breath hold, images have been collected simultaneously from both
breasts at a rate of 1.7 frames per second with 32 sources and 64 detectors per breast and four wavelengths of light at
765, 805, 827, and 905nm. Initial results involving one healthy volunteer and one breast cancer patient support the
potential use of dynamic imaging for breast cancer detection.
It is well acknowledged that treatment efficacy could be increased and unnecessary toxicities reduced if a rapid
assessment strategy were available to allow individual tailoring of cancer therapy. In this work we focus on using optical
tomographic imaging to detect tumor response to anti-angiogenic treatment within the first 5 days of therapy. For this
study we used two models with well-characterized and divergent responses to inhibition of vascular endothelial growth
factor (VEGF). SK-NEP and NGP cells were implanted intrarenally into NCR nude mice and the resulting tumors were
monitored until a threshold of 1-2 g was reached. Optical tomographic imaging with a dual-wavelength (λ = 765nm and
830nm) continuous wave system, was performed prior to the first treatment with the anti-VEGF bevacizumab (BV), as
well as 1, 3, and 5 days later. We found that the SK-NEP tumor model, known to be responsive to BV treatment, shows
a decrease in hemoglobin levels over the 5 days. Mice implanted with the NGP tumor model, known to be less
responsive to treatment, do not show such decreases. These results were further validated with histopathological findings
that showed a decrease in tumor vascularization in treated SK-NEP mice. These results suggest that optical tomography
is a promising tool for monitoring early tumor response to drug therapy.
KEYWORDS: Digital signal processing, Imaging systems, Breast, Signal processing, Optical fibers, Signal detection, Breast cancer, Breast imaging, Sensors, Tissue optics
Breast cancer characteristics such as angiogenesis and hypoxia can be quantified by using optical
tomography imaging to observe the hemodynamic response to an external stimulus. A digital near-infrared
tomography system has been developed specifically for the purpose of dynamic breast imaging. It
simultaneously acquires four frequency encoded wavelengths of light at 765, 808, 827, and 905nm in order
to facilitate the functional imaging of oxy- and deoxy-hemoglobin, lipid concentration and water content.
The system uses 32 source fibers to simultaneously illuminate both breasts. There are 128 detector fibers,
64 fibers for each breast, which deliver the detected light to silicon photo-detectors. The signal is
conditioned by variable gain amplifiers and filters and is quantized by an analog to digital converter
(ADC). The sampled signal is then passed on for processing using a Digital Signal Processor (DSP) prior
to display on a host computer. The system can acquire 2.23 frames per second with a dynamic range of
236 dB.
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