Near-infrared diffuse optical tomography (DOT) has demonstrated a great potential as an adjunct modality for differentiation of malignant and benign breast lesions and for monitoring treatment response in patients with locally advanced breast cancers. The path toward commercialization of DOT techniques depends upon the improvement of robustness and user-friendliness of this technique in hardware and software. In this study, we introduce our recently developed ultrasound-guided DOT system, which has been improved in system compactness, robustness, and user-friendliness by custom-designed electronics, automated data preprocessing, and implementation of a new two-step reconstruction algorithm. The system performance has been tested with several sets of solid and blood phantoms and the results show accuracy in reconstructed absorption coefficients as well as blood oxygen saturation. A clinical example of a breast cancer patient, who was undergoing neoadjuvant chemotherapy, is given to demonstrate the system performance.
Initial feasibility of a spatial frequency domain imaging system was studied consisting of a hand held miniaturized projector and a rigid endoscope. Three wavelengths and two spatial frequencies were used for imaging. The system was calibrated using tissue mimicking phantoms. In vivo imaging was performed on five live mouse tumor models, and the absorption, scattering, hemoglobin oxygen saturation was measured. The initial promising results indicate that the spatial frequency domain imaging can a very useful tool for quantitative wide field tissue evaluation during minimally invasive image guided surgery.
KEYWORDS: In vivo imaging, Photoacoustic tomography, Acquisition tracking and pointing, Luminescence, Blood, Absorbance, Photoacoustic spectroscopy, Absorption, Near infrared, Toxicity, Tumors, Argon, Signal generators
A PEGylated quinoline-annulated porphyrin derivative was synthesized as in vivo photoacoustic tomography contrast agent. It possesses high solubility and stability in water and phosphate-buffered saline. No toxicity sign was observed in BALB/c mice. The dye demonstrates a 4-fold higher photoacoustic signal generation efficiency compared to fresh rat blood. Injection of the dye results in a significant enhancement of in vivo PAT images of murine tumors. Analysis of the mouse urine after injection revealed an unaltered renal filtration of the contrast agent.
We have developed the ultrasound (US)-guided diffuse optical tomography technique to assist US diagnosis of breast cancer and to predict neoadjuvant chemotherapy response of patients with breast cancer. The technique was implemented using a hand-held hybrid probe consisting of a coregistered US transducer and optical source and detector fibers which couple the light illumination from laser diodes and photon detection to the photomultiplier tube detectors. With the US guidance, diffused light measurements were made at the breast lesion site and the normal contralateral reference site which was used to estimate the background tissue optical properties for imaging reconstruction. However, background optical properties were affected by the chest wall underneath the breast tissue. We have analyzed data from 297 female patients, and results have shown statistically significant correlation between the fitted optical properties (μa and μs′) and the chest wall depth. After subtracting the background μa at each wavelength, the difference of computed total hemoglobin (tHb) between malignant and benign lesion groups has improved. For early stage malignant lesions, the area-under-the-receiver operator characteristic curve (AUC) has improved from 88.5% to 91.5%. For all malignant lesions, the AUC has improved from 85.3% to 88.1%. Statistical test has revealed the significant difference of the AUC improvements after subtracting background tHb values.
According to the World Health Organization, breast cancer is the most common cancer among women worldwide, claiming the lives of hundreds of thousands of women each year. Near infrared diffuse optical tomography (DOT) has demonstrated a great potential as an adjunct modality for differentiation of malignant and benign breast lesions and for monitoring treatment response of patients with locally advanced breast cancers. The path toward commercialization of DOT techniques depends upon the improvement of robustness and user-friendliness of this technique in hardware and software. In the past, our group have developed three frequency domain prototype systems which were used in several clinical studies. In this study, we introduce our newly under development US-guided DOT system which is being improved in terms of size, robustness and user friendliness by several custom electronic and mechanical design. A new and robust probe designed to reduce preparation time in clinical process. The processing procedure, data selection and user interface software also updated. With all these improvements, our new system is more robust and accurate which is one step closer to commercialization and wide use of this technology in clinical settings. This system is aimed to be used by minimally trained user in the clinical settings with robust performance. The system performance has been tested in the phantom experiment and initial results are demonstrated in this study. We are currently working on finalizing this system and do further testing to validate the performance of this system. We are aiming toward use of this system in clinical setting for patients with breast cancer.
We have developed ultrasound (US)-guided diffuse optical tomography (DOT) technique to assist US diagnosis of
breast cancer and to predict neoadjuvant chemotherapy response of breast cancer patients. The technique was
implemented using a hand-held hybrid probe consisting co-registered US transducer and optical source and detector
fibers which couple the light illumination from laser diodes and photon detection to PMT detectors. With the US
guidance, diffused light measurements were made at the breast lesion site and the normal contralateral reference site
which was used to estimate the background tissue optical properties for imaging reconstruction. However, background
optical properties were affected by the chest wall underneath the breast tissue. In this study, we have analyzed data
from 297 female patients and results have shown statistical significant correlation between fitted optical properties (μa
and μs’) and the chest wall depth detected by a boundary detection algorithm applied to co-registered US images (r <
0.27, p < 1.0 x 10-4). After subtracting the background total hemoglobin (tHb) computed with μa at each wavelength,
the difference between malignant and benign lesion groups has improved. The Area-under-the- ROC curve (AUC)
has improved from 88.5% to 91.5% (sensitivity improved from 85.0% to 87.5% and specificity from 90.2% to 92.6%).
Statistical test has revealed significant difference of the AUC improvements after subtracting background tHb values.
Tissue diagnostic features generated by a bimodal technique integrating scanning time-resolved fluorescence spectroscopy (TRFS) and ultrasonic backscatter microscopy (UBM) are investigated in an in vivo hamster oral carcinoma model. Tissue fluorescence is excited by a pulsed nitrogen laser and spectrally and temporally resolved using a set of filters/dichroic mirrors and a fast digitizer, respectively. A 41-MHz focused transducer (37-μm axial, 65-μm lateral resolution) is used for UBM scanning. Representative lesions of the different stages of carcinogenesis show that fluorescence characteristics complement ultrasonic features, and both correlate with histological findings. These results demonstrate that TRFS-UBM provide a wealth of co-registered, complementary data concerning tissue composition and structure as it relates to disease status. The direct co-registration of the TRFS data (sensitive to surface molecular changes) with the UBM data (sensitive to cross-sectional structural changes and depth of tumor invasion) is expected to play an important role in pre-operative diagnosis and intra-operative determination of tumor margins.
We report the development and validation of an intravascular rotary catheter for bimodal interrogation of arterial pathologies. This is based on a point-spectroscopy scanning time-resolved fluorescence spectroscopy technique enabling reconstruction of fluorescence lifetime images (FLIm) and providing information on arterial intima composition and intravascular ultrasound (IVUS) providing information on arterial wall morphology. The catheter design allows for independent rotation of the ultrasonic and optical channels within an 8 Fr outer diameter catheter sheath and integrates a low volume flushing channel for blood removal in the optical pathways. In the current configuration, the two channels consist of (a) a standard 3 Fr IVUS catheter with single element transducer (40 MHz) and (b) a side-viewing fiber optic (400 μm core). Experiments conducted in tissue phantoms showed the ability of the catheter to operate in an intraluminal setting and to generate coregistered FLIm and IVUS in one pull-back scan. Current results demonstrate the feasibility of the catheter for simultaneous bimodal interrogation of arterial lumen and for generation of robust fluorescence lifetime data under IVUS guidance. These results facilitate further development of a FLIm-IVUS technique for intravascular diagnosis of atherosclerotic cardiovascular diseases including vulnerable plaques.
We report the development and validation of an intravascular rotary catheter that enables bi-modal interrogation of
arterial pathologies based on fast-frame time-resolved fluorescence spectroscopy (TRFS) and intravascular ultrasound
(IVUS). The catheter is based on a parallel design that allows for independent rotation of the ultrasonic and optical
channels within an 8 Fr outer diameter catheter sheath and integrates a low volume flushing channel for blood removal
in the optical pathways. In current configuration, the two channels consist of a) a standard 8 Fr IVUS catheter with single
element transducer (15 MHz) and b) a side-viewing UV-grade silica/silica fiber optic (400 μm core). The catheter is
terminated by a small (0.82 mm internal diameter) polyimide tube to keep the fiber stable within the sheath. To clear the
field of view from blood, a saline solution can be flushed in a sheath channel, concentric with the fiber optic, through the
tube and in a radial opening aligned with the fiber's optical beam. The flushing function was optimized with a
computational fluid dynamics (CFD) model pursued in a parallel study. The ability of the catheter to operate in
intraluminal setting in blood flow, the effect of probe-to-tissue distance on optical signal and ability to generate co-registered
TRFS and IVUS data were demonstrated in blood vessel phantoms. Current results demonstrate the feasibility
of the described catheter for parallel interrogation of vessel walls based on TRFS and IVUS and to generate robust TRFS
data. These results facilitate further development of a bi-modal TRFS-IVUS technique for intravascular diagnosis of
atherosclerotic cardiovascular diseases including vulnerable plaques.
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