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Biomedical subjects

Quing Zhu

Publications and source records attributed to Quing Zhu.

At least 19 recordsLinked to original sources

Analytical solution for light propagation in a two-layer tissue structure with a tilted interface for breast imaging.

Reflectance measurement of breast tissue is influenced by the underlying chest wall, which is often tilted as seen by the detection probe. We develop an analytical solution of light propagation in a two-layer tissue structure with tilted interface and refractive index difference between the layers. We validate the analytical solution with Monte Carlo simulations and phantom experiments, and a good agreement is seen. The influence of varying the tilting angle of the interface on the reflectance is discussed for two types of layered structures. Further, we apply the developed analytical solution to obtain the optical properties of breast tissue and chest wall from clinical data. Inverse calculation using the developed solution applied to the data obtained from Monte Carlo simulations shows that the optical properties of both layers are obtained with higher accuracy as compared to using a simple two-layer model ignoring the interface tilt. This is expected to improve the accuracy in estimating the optical properties of breast tissue, thus enhancing the accuracy of optical tomography of breast tumors.

Algorithms↗

Optimal probing of optical contrast of breast lesions of different size located at different depths by US localization.

We report a frequency domain optical tomography system utilizing three RF modulation frequencies, which are optimized for probing breast lesions of different size located at different depths. A real-time co-registered ultrasound scanner is used to provide on-site estimation of lesion size and location. Based on the lesion information, an optimal light modulation frequency can be selected, which may yield more accurate estimates of lesion angiogenesis and hypoxia. Phantom experiments have demonstrated that a high modulation frequency, such as 350Mhz, is preferable for probing small lesions closer to the surface while a low modulation frequency, such as 50Mhz, is desirable for imaging deeper and larger lesions. A clinical example of a large invasive carcinoma is presented to demonstrate the application of this novel technique.

Algorithms↗

Estimation of chest-wall-induced diffused wave distortion with the assistance of ultrasound.

The chest-wall layer underneath breast tissue consists of muscles and bones, which induce distortion in near-infrared diffused waves measured at distant source--detector pairs when reflection geometry is used. A priori information on chest-wall depth obtained from coregistered real-time ultrasound can be used to assist in the removal of distant measurements. We applied Monte Carlo simulation to a simple two-layer model consisting of breast tissue and a chest wall to investigate chest-wall-induced distortion. The Monte Carlo method indicates that, when more than 50% of the received photons travel through the breast tissue layer before being detected, the detected signal may be useful for image reconstruction. The results of phantom experiments obtained from the two-layer model further validate the distortion problem and demonstrate imaging improvement after distant measurements have been filtered out. Clinical examples have shown similar imaging improvements on reconstructed absorption maps. Clinical data obtained from 20 patients with the chest-wall depths of less than 2 cm from the skin surface suggest that the cutoff distances of distorted measurements are largely related to the chest-wall depth and are relatively independent of the optical properties of tissue.

Algorithms↗

Characterization of dentin, enamel, and carious lesions by a polarization-sensitive optical coherence tomography system.

Enamel and dentin are the primary components of human teeth. Both of them have a strong polarization effect. We designed a polarization-sensitive optical coherence tomography (PSOCT) system to study the spatially resolved scattering and polarization phenomena of teeth. The system is constructed in free space to avoid the complexity of polarization control in fiber-based PSOCT. The structural features of enamel were evaluated in five human teeth that had no visible evidence of caries. The teeth were subsequently sectioned in mesial distal orientation and coronal orientation. Then the structural aspects of dentin were evaluated. OCT images were made of the mantel dentin near the dentin-enamel junction. Five teeth with interproximal and occlusal caries were also studied. With two channel and phase-retardation images, PSOCT provided better functional contrast and more detailed structural information than conventional OCT. For a better description of the measured PSOCT data, we classify these features by two types, i.e., the local textural features and the global structural features. This study indicates that PSOCT has the potential to be a powerful tool for research of dental formation and caries diagnosis.

Algorithms↗

Direct bidirectional angle-insensitive imaging of the flow signal intensity in Doppler optical coherence tomography.

We introduce a new method, to our knowledge, for direct detection of flow signal intensity by stationary target rejection. In our system, two delay lines are constructed with identical scanning speed and ranging depth. One delay line is used for depth ranging as well as phase modulation, and the other one acts as a full-range retroreflector (FRRR). The signal from this FRRR carries the overall features of local phase modulation, and it is used as the local oscillator for coherent demodulation. With this setup, stationary targets can be rejected at a 4-kHz high-pass cutoff frequency of the filter that follows the demodulator, compared with 20 kHz for conventional fixed-frequency demodulation. This technique features angle insensitivity and provides flow direction as well by implementing standard in-phase and quadrature detection. Besides the direct directional detection of flow signal intensity, flow speed information can be acquired with postprocessing.

Hemorheology↗

Benign versus malignant breast masses: optical differentiation with US-guided optical imaging reconstruction.

PURPOSE: To investigate prospectively the feasibility of using optical tomography with ultrasonographic (US) localization to differentiate malignant from benign breast masses and to compare optical tomography with color Doppler US. MATERIALS AND METHODS: The study was approved by the local internal review board committee and by the Human Subjects Research Review Board of Army Medical Research and Materiel Command. Signed informed consent was obtained, and the study was HIPAA compliant. Between May 2003 and March 2004, 65 consecutive women (mean age, 51 years; age range, 24-80 years) with 81 breast lesions underwent US-guided biopsy and were scanned with a combined imager. The hand-held probe, which consisted of a centrally located US transducer surrounded by near-infrared sensors, was used to simultaneously acquire coregistered US images and optical data. The lesion location obtained at US was used to guide optical imaging reconstruction. Light absorption was measured at two wavelengths. From these measurements, tumor angiogenesis was assessed on the basis of calculated total hemoglobin concentration. A Student t distribution was used to calculate the statistical significance of mean maximum and mean average hemoglobin concentrations obtained in malignant and benign lesion groups, and P < .001 was considered to indicate a statistically significant difference. RESULTS: Biopsy results revealed eight early stage invasive carcinomas (malignant group) and 73 benign lesions (benign group). The mean maximum and mean average hemoglobin concentrations in the malignant group were 122 micromol/L +/- 26.8 (+/- standard deviation) and 88 micromol/L +/- 24.5, respectively. The mean maximum and mean average hemoglobin concentrations in the benign group were 55 micromol/L +/- 24.8 and 38 micromol/L +/- 17.4, respectively. Both the maximum and average total hemoglobin concentrations were significantly higher in the malignant group compared with the benign group (P < .001). When a maximum hemoglobin concentration of 95 micromol/L was used as the threshold value, the sensitivity, specificity, positive predictive value, and negative predictive value of optical tomography were 100%, 96%, 73%, and 100%, respectively, and the sensitivity, specificity, positive predictive value, and negative predictive value of color Doppler US were 63%, 69%, 19%, and 94%, respectively. CONCLUSION: Findings indicate that optical tomography with US localization is feasible for differentiating benign and early stage malignant breast lesions.

Adult↗

Optical tomography with ultrasound localization: initial clinical results and technical challenges.

Optical tomography with ultrasound localization utilizes co-registered ultrasound lesion structure information to guide optical imaging reconstruction. A hand-held probe consisting of a commercial ultrasound transducer and near infrared optical imaging sensors was used to simultaneously acquire ultrasound images and optical measurements. A dual-mesh scheme was used to map the ultrasound-visible lesions to finer-grid lesion regions and coarser-grid background regions for optical imaging reconstruction. As a result, optical imaging reconstruction was well-conditioned for inverse mapping of lesion hemoglobin concentration and blood oxygen saturation. Initial clinical results have shown that early stage invasive cancers may be distinguished by a two-fold greater total hemoglobin concentration compared with fibroadenomas and other benign lesions. Initial results of advanced cancers have shown that the hemoglobin distribution is highly distorted and heterogeneous and the distorted distributions correlate with histological microvessel density counts and could be used to assess chemotherapy response.

Adenocarcinoma↗

Utilizing optical tomography with ultrasound localization to image heterogeneous hemoglobin distribution in large breast cancers.

PURPOSE: Angiogenesis in advanced breast cancers is highly distorted and heterogeneous. Noninvasive imaging that can monitor angiogenesis may be invaluable initially for diagnosis and then for assessing tumor response to treatment. By combining ultrasound (US) and near-infrared (NIR) optical imaging, a reliable new technique has emerged for localizing and characterizing tumor angiogenesis within the breast. METHODS: This new technique employs a commercial US transducer coupled with an array of NIR optical fibers mounted on a hand-held probe. The US image is used for lesion localization and for guiding optical imaging reconstruction. Optical sensors are used for imaging tumor total hemoglobin distribution, which is directly related to tumor angiogenesis. RESULTS: Six large breast carcinomas were studied and microvessel density count was then performed on tissue samples obtained from these cancers. Two patients had locally advanced breast cancers and received neoadjuvant chemotherapy for 3 months. In one patient, before chemotherapy, the total hemoglobin distribution showed a high concentration at the cancer periphery; the distribution was later confined to the core area after 3 months of treatment. In another patient, as treatment progressed, the maximum hemoglobin concentration decreased from 255.3, to 147.5, to 76.9 micromol/l with an associated reduction in spatial extension. The other four patients had cancers of 2.0 to 3.0 cm in size and were imaged either at the time of core biopsy or definitive surgery. The histologic microvessel density counts from these tumor samples correlate to hemoglobin distributions with a correlation coefficient of 0.64 (P < .05). CONCLUSION: These initial results suggest that this new imaging technique may have great potential in imaging the heterogeneous vascular distribution of larger breast cancers in vivo and in monitoring treatment-related changes in angiogenesis during chemotherapy.

Adenocarcinoma↗

Dual-mesh optical tomography reconstruction method with a depth correction that uses a priori ultrasound information.

A dual-mesh reconstruction method with a depth correction for near-infrared diffused wave imaging with ultrasound localization is demonstrated by use of phantoms and clinical cancer cases. Column normalization is applied to the weight matrix obtained from the Born approximation to correct the depth-dependent problem in the reconstructed absorption maps as well as in the total hemoglobin concentration maps. With the depth correction, more uniform absorption maps for target layers at different depths are obtained from the phantoms, and the correlation between the reconstructed hemoglobin concentration maps of deeply located, large cancers and the histological microvessel density counts are dramatically improved.

Adult↗

Quantifying labial blood flow using optical Doppler tomography.

OBJECTIVES: Changes in the oral microvasculature occur in a variety of diseases. Optical Doppler tomography (ODT) combines laser Doppler flowmetry with optical coherence tomography (OCT) to produce high-resolution tomographic images of biological tissues that also detect the velocity and direction of blood flow. The objective of this study was to determine the feasibility of ODT to image labial blood flow. A prototype ODT imaging system was constructed that characterized and measured labial blood flow in healthy subjects. MATERIALS AND METHODS: A prototype ODT instrument was constructed using a diode light source with a central wavelength of 1300 nanometers, a 40-nanometer spectral width and 2.4 microwatts output power. To verify the accuracy of the system, the flow rates of a phantom material (Intralipid) pumped through a capillary tube at various speeds was measured. To evaluate the clinical feasibility of the ODT prototye, the mucosal aspect of the upper and lower lips at the midline was imaged in 9 healthy volunteers. The sample arm of the instrument consisted of a fiberoptic probe with a 2-mm in diameter polished glass lens attached to the end. The probe was placed approximately 3 mm from the mucosal surface of the lip and oriented perpendicular to the surface. A motorized translation stage moved the fiber in a superior to inferior direction while the subject's head was stabilized by placing the chin into a chin rest. Imaging time for a 12-mm x 2.5-mm scan was approximately 64 seconds. RESULTS: The phantom experiments revealed that accuracy of this novel ODT prototype to measure flow was within 5%. In vivo labial blood flow velocity ranged from 11.8 to 43.1 mm/second in the upper lip and 8.2 to 53.2 mm/second in the lower lip. There were no statistically significant differences between flow rates in the upper and lower lips. OCT images and Doppler velocity signals were successfully integrated producing in vivo images of labial blood in all of the subjects (15 images). The resulting cross-sectional images revealed microscopic details of labial structures and, to the best of our knowledge, are the first ODT images of the labial microvasculature. CONCLUSIONS: The results of this in vivo study prove the feasibility of ODT to quantify labial blood flow and produce high spatial resolution images specifically localizing vessels anatomically. ODT provides both flow speed and flow direction information. ODT is noninvasive and offers the advantages of high volumetric flow sensitivity.

Anatomy, Cross-Sectional↗

Simultaneous optical coherence tomography imaging and beta particle detection.

A prototype hybrid catheter device designed for imaging and detection of vascular diseases is introduced. The prototype device integrates a high-resolution optical coherent tomography probe and a high-sensitivity beta detector into a single unit. With this prototype device we demonstrate the feasibility of simultaneous optical coherence tomography imaging and detection of beta particles.

Beta Particles↗

Quantifying Doppler angle and mapping flow velocity by a combination of Doppler-shift and Doppler-bandwidth measurements in optical Doppler tomography.

Recently we introduced a novel procedure that estimates Doppler angle and flow velocity simultaneously by combining Doppler-shift and Doppler-bandwidth measurements with a conventional single-beam optical Doppler tomography device. Here we validate this method experimentally with two Intralipid flow setups that correspond to fixed Doppler angle and fixed flow speed. One set of data has a fixed flow speed of 53.6 mm/s with a Doppler angle that changes from 56 degrees to 90 degrees; the other has a fixed Doppler angle of 80 degrees with flow speed that changes from 18.5 to 141.9 mm/s. As obtained with the method introduced here, the Doppler-angle estimation accuracies of the two sets are 97.6% and 98.2%, respectively, and the estimation accuracies of flow speeds of the two sets are 94.3% and 90.4%, respectively.

Algorithms↗

Simultaneous reconstruction of absorption and scattering maps with ultrasound localization: feasibility study using transmission geometry.

We report the experimental results of the simultaneous reconstruction of absorption and scattering coefficient maps with ultrasound localization. Near-infrared (NIR) data were obtained from frequency domain and dc systems with source and detector fibers configured in transmission geometry. High- or low-contrast targets located close to either the boundary or the center of the turbid medium were reconstructed by using NIR data only and NIR data with ultrasound localization. Results show that the mean reconstructed absorption coefficient and the spatial distribution of the absorption map have been improved significantly with ultrasound localization. The improvements in the mean scattering coefficient and the spatial distribution of the scattering coefficient are moderate. When both the absorption and the scattering coefficients are reconstructed the performance of the frequency-domain systemis much better than that of the dc system.

Algorithms↗

Doppler angle and flow velocity mapping by combined Doppler shift and Doppler bandwidth measurements in optical Doppler tomography.

Accurate estimation of flow velocity requires measurement of Doppler angle, which is not available in general clinical applications. We describe a novel method of direct Doppler angle and flow velocity mapping that uses a conventional single-beam optical Doppler tomography system. The Doppler angle is estimated by combination of Doppler shift and Doppler bandwidth measurements, and flow velocity is calculated from the Doppler shift and the estimated Doppler angle. In vivo study of lip microvascularization demonstrates that this method is capable of providing both flow speed and flow direction information.

Blood Flow Velocity↗

Imaging tumor angiogenesis by use of combined near-infrared diffusive light and ultrasound.

A novel two-step reconstruction scheme using a combined near-infrared and ultrasound technique and its utility in imaging distributions of optical absorption and hemoglobin concentration of breast lesions are demonstrated. In the first-step image reconstruction, the entire tissue volume is segmented based on initial coregistered ultrasound measurements into lesion and background regions. Reconstruction is performed by use of a finer grid for lesion region and a coarse grid for the background tissue. As a result, the total number of voxels with unknown absorption can be maintained on the same order of total measurements, and the matrix with unknown total absorption distribution is appropriately scaled for inversion. In the second step, image reconstruction is refined by optimization of lesion parameters measured from ultrasound images. It is shown that detailed distributions of wavelength-dependent absorption and hemoglobin concentration of breast carcinoma can be obtained with the new reconstruction scheme.

Adult↗

Quantitative assessment of flow velocity-estimation algorithms for optical Doppler tomography imaging.

We present a quantitative comparison of three categories of velocity estimation algorithms, including centroid techniques (the adaptive centroid technique and the weighted centroid technique), the sliding-window filtering technique, and correlation techniques (autocorrelation and cross correlation). We introduce, among these five algorithms, two new algorithms: weighted centroid and sliding-window filtering. Simulations and in vivo blood flow data are used to assess the velocity estimation accuracies of these algorithms. These comparisons demonstrate that the sliding-window filtering technique is superior to the other techniques in terms of velocity estimation accuracy and robustness to noise.

Algorithms↗

Time-resolved optical measurements with spread spectrum excitation.

We propose a novel method for measuring time-dependent optical quantities. A train of excitation pulses modulated by a pseudorandom bit sequence is used as the light source, and a cross-correlation scheme is used to retrieve the impulse response. Simulation results of the temporal point-spread function of a diffusive wave are provided, as well as experimental results of a fluorescence decay profile. It is demonstrated that our new time-resolved technique can lead to high signal-to-noise ratios and short data acquisition times. A fluorescence-time-dependent suppression process was also been discovered.

Journal Article↗

Ultrasound-guided optical tomographic imaging of malignant and benign breast lesions: initial clinical results of 19 cases.

The diagnosis of solid benign and malignant tumors presents a unique challenge to all noninvasive imaging modalities. Ultrasound is used in conjunction with mammography to differentiate simple cysts from solid lesions. However, the overlapping appearances of benign and malignant lesions make ultrasound less useful in differentiating solid lesions, resulting in a large number of benign biopsies. Optical tomography using near-infrared diffused light has great potential for imaging functional parameters of 1) tumor hemoglobin concentration, 2) oxygen saturation, and 3) metabolism, as well as other tumor distinguishing characteristics. These parameters can differentiate benign from malignant lesions. However, optical tomography, when used alone, suffers from low spatial resolution and target localization uncertainty due to intensive light scattering. Our aim is to combine diffused light imaging with ultrasound in a novel way for the detection and diagnosis of solid lesions. Initial findings of two early-stage invasive carcinomas, one combined fibroadenoma and fibrocystic change with scattered foci of lobular neoplasia/lobular carcinoma in situ, and 16 benign lesions are reported in this paper. The invasive cancer cases reveal about two-fold greater total hemoglobin concentration (mean 119 micromol) than benign cases (mean 67 micromol), and suggest that the discrimination of benign and malignant breast lesions might be enhanced by this type of achievable optical quantification with ultrasound localization. Furthermore, the small invasive cancers are well localized and have wavelength-dependent appearance in optical absorption maps, whereas the benign lesions appear diffused and relatively wavelength-independent.

Adult↗