Biomedical subjects

Keith D Paulsen

Publications and source records attributed to Keith D Paulsen.

At least 37 records · Page 2Linked to original sources

PubMed2005

Near-infrared characterization of breast tumors in vivo using spectrally-constrained reconstruction.

Multi-wavelength Near-Infrared (NIR) Tomography was utilized in this study to non-invasively quantify physiological parameters of breast tumors using direct spectral reconstruction. Frequency domain NIR measurements were incorporated with a new spectrally constrained direct chromophore and scattering image reconstruction algorithm, which was validated in simulations and experimental phantoms. Images of total hemoglobin, oxygen saturation, water, and scatter parameters were obtained with higher accuracy than previously reported. Using this spectral approach, in vivo NIR images are presented and interpreted through a series of case studies (n=6 subjects) having differing abnormalities. The corresponding mammograms and ultrasound images are also evaluated. Three of six cases were malignant (infiltrating ductal carcinomas) and showed higher hemoglobin (34-86% increase), a reduction in oxygen saturation, an increase in water content as well as scatter changes relative to surrounding normal tissue. Three of six cases were benign, two of which were diagnosed with fibrocystic disease and showed a dominant contrast in water, consistent with fluid filled cysts. Scatter amplitude was the main source of contrast in the volunteer with the benign condition fibrosis, which typically contains denser collagen tissue. The changes monitored correspond to physiological changes associated with angiogenesis, hypoxia and cell proliferation anticipated in cancers. These changes represent potential diagnostic indicators, which can be assessed to characterize breast tumors.

Adult↗

PubMed2005

Cortical surface tracking using a stereoscopic operating microscope.

OBJECTIVE: To measure and compensate for soft tissue deformation during image-guided neurosurgery, we have developed a novel approach to estimate the three-dimensional (3-D) topology of the cortical surface and track its motion over time. METHODS: We use stereopsis to estimate the 3-D cortical topology during neurosurgical procedures. To facilitate this process, two charge-coupled device cameras have been attached to the binocular optics of a stereoscopic operating microscope. Before surgery, this stereo imaging system is calibrated to obtain the extrinsic and intrinsic camera parameters. During surgery, the 3-D shape of the cortical surface is automatically estimated from a stereo pair of images and registered to the preoperative image volume to provide navigational guidance. This estimation requires robust matching of features between the images, which, when combined with the camera calibration, yields the desired 3-D coordinates. After the 3-D cortical surface has been estimated from stereo pairs, its motion is tracked by comparing the current surface with its previous locations. RESULTS: We are able to estimate the 3-D topology of the cortical surface with an average error of less than 1.2 mm. Executing on a 1.1-GHz Pentium machine, the 3-D estimation from a stereo pair of 1024 x 768 resolution images requires approximately 60 seconds of computation. By applying stereopsis over time, we are able to track the motion of the cortical surface, including the pulsatile movement of the cortical surface, gravitational sag, tissue bulge as a result of increased intracranial pressure, and the parenchymal shape changes associated with tissue resection. The results from 10 surgical patients are reported. CONCLUSION: We have demonstrated that a stereo vision system coupled to the operating microscope can be used to efficiently estimate the dynamic topology of the cortical surface during surgery. The 3-D surface can be coregistered to the preoperative image volume. This unique intraoperative imaging technique expands the capability of the current navigational system in the operating room and increases the accuracy of anatomic correspondence with preoperative images through compensation for brain deformation.

Adult↗

PubMed2004

Absorption and scattering imaging of tissue with steady-state second-differential spectral-analysis tomography.

A novel approach to reconstructing both the absorption and the scattering properties of a turbid medium simultaneously from steady-state broadband spectral measurements is presented that utilizes second-differential fitting to the water spectrum to estimate the optical path length in tissue. Theoretical and experimental evidence is provided to demonstrate the robust accuracy of the spectroscopy approach and reconstructed absorption images. The steady-state broadband CCD system has the potential to provide accurate chromophore imaging without the technological complexity of time- or frequency-domain systems.

Absorption↗

PubMed2004

Breast deformation modelling for image reconstruction in near infrared optical tomography.

Near infrared tomography (NIR) is a novel imaging technique that can be used to reconstruct tissue optical properties from measurements of light propagation through tissue. More specifically NIR measurements over a range of wavelengths can be used to obtain internal images of physiologic parameters and these images can be used to detect and characterize breast tumour. To obtain good NIR measurements, it is essential to have good contact between the optical fibres and the breast which in-turn results in the deformation of the breast due to the soft plasticity of the tissue. In this work, a tissue deformation model of the female breast is presented that will account for the altered shape of the breast during clinical NIR measurements. Using a deformed model of a breast, simulated NIR data were generated and used to reconstruct images of tissue absorption and reduced scatter using several assumptions about the imaging domain. Using either a circular or irregular 2D geometry for image reconstruction produces good localization of the absorbing anomaly, but it leads to degradation of the image quality. By modifying the assumptions about the imaging domain to a 3D conical model, with the correct diameter at the plane of NIR measurement, significantly improves the quality of reconstructed images and helps reduce image artefacts. Finally, assuming a non-deformed breast shape for image reconstruction is shown to lead to poor quality images since the geometry of the breast is greatly altered, whereas using the correct deformed geometry produces the best images.

Algorithms↗

PubMed2004

Non-invasive assessment of radiation injury with electrical impedance spectroscopy.

A detailed understanding of non-targeted normal tissue response is necessary for the optimization of radiation treatment plans in cancer therapy. In this study, we evaluate the ability of electrical impedance spectroscopy (EIS) to non-invasively determine and quantify the injury response in soft tissue after high dose rate (HDR) irradiation, which is characterized by large localized dose distributions possessing steep spatial gradients. The HDR after-loading technique was employed to irradiate small volumes of muscle tissue with single doses (26-52 Gy targeted 5 mm away from the source). Impedance measurements were performed on 29 rats at 1, 2 and 3 month post-irradiation, employing 31 frequencies in the 1 kHz to 1 MHz range. Over the first 3 months, conductivity increased by 48% and 26% following target doses of 52 Gy and 26 Gy 5 mm from the HDR source, respectively. Injury, assessed independently through a grid-based scoring method showed a quadratic dependence on distance from source. A significant injury (50% of cells atrophied, necrotic or degenerating) in 1.2% of the volume, accompanied by more diffuse injury (25% of cells atrophied, necrotic or degenerating) in 9% of the tissue produced a conductivity increase of 0.02 S m(-1) (8% over a baseline of 0.24 S m(-1)). This was not statistically significant at p = 0.01. Among treatment groups, injury differences in 22% of the volume led to statistically significant differences in conductivity of 0.07 S m(-1) (23% difference in conductivity). Despite limitations, the success of EIS in detecting responses in a fraction of the tissue probed, during these early post-irradiation time-points, is encouraging. Electrical impedance spectroscopy may provide a useful metric of atrophy and the development of fibrosis secondary to radiation that could be further developed into a low-cost imaging method for radiotherapy monitoring and assessment.

Animals↗

PubMed2004

Automated region detection based on the contrast-to-noise ratio in near-infrared tomography.

The contrast-to-noise ratio (CNR) was used to determine the detectability of objects within reconstructed images from diffuse near-infrared tomography. It was concluded that there was a maximal value of CNR near the location of an object within the image and that the size of the true region could be estimated from the CNR. Experimental and simulation studies led to the conclusion that objects can be automatically detected with CNR analysis and that our current system has a spatial resolution limit near 4 mm and a contrast resolution limit near 1.4. A new linear convolution method of CNR calculation was developed for automated region of interest (ROI) detection.

Artifacts↗

PubMed2004

Variation in breast EIT measurements due to menstrual cycle.

We conducted a short study on 8 volunteer subjects to establish whether physiological changes occurring as a result of the menstrual cycle affect tissue electrical properties. For this study subjects submitted to electrical impedance tomographic breast measurement four times, over two cycles at two different points in the cycle. Statistical analysis based on reconstructed values of conductivity and permittivity were conducted using the t-test for difference of means. The results were inconsistent, with some subjects showing a difference between the two phases and in all tests, while others showed differences only in some of the tests. At this time we can only conclude that a difference is more likely than not, although it could be a phenomenon only measurable in some individuals and not others. It seems that a larger study may be in order to establish this fact definitively.

Adult↗

PubMed2004

Multi-frequency electrical impedance tomography of the breast: new clinical results.

Electrical impedance tomography (EIT) has been used in the recent past for a number of clinical applications. In this work we present recent tomographic and spectroscopic findings for breast imaging from clinical exams completed at Dartmouth. The results presented here are based on 18 normal and 24 abnormal subjects. The participants were classified as normal or abnormal using the American College of Radiology (ACR) indexing system for mammograms. The EIT data were collected for ten discrete frequencies in the range 10 kHz-1 MHz using a single array of 16 electrodes. The finite element method was used to reconstruct the images. The images were examined visually and were compared with mammograms. The results were also analyzed based on zonal averages of property values and breast tissue radiodensities. Statistical analysis showed a significance difference between the mean conductivity and permittivity values of normal and abnormal subjects for various zones defined on the reconstructed images. Tissues with high radiodensity also had increased conductivity and permittivity.

Breast↗

PubMed2004

Feasibility studies of electrical impedance spectroscopy for early tumor detection in rats.

Electrical impedance spectroscopy (EIS) has been previously reported as a technique for non invasive assessment of tissue change. Our previous in vivo studies demonstrated the ability of EIS to non-invasively detect and longitudinally follow tumor growth. This study was designed to determine the ability of EIS to detect tumors at a very early stage post-implantation. Complex impedance measurements were collected from eight rats with one control and one tumor implanted leg six or seven days after tumor cell inoculation. Legs were also imaged with computed tomography (CT) and ultrasound (US) in an effort to determine EIS resolution and sensitivity. Six of the animals were sacrificed immediately after imaging, and tissue was collected for histology and later co-registration of the pathology with the imaging techniques. Results show that EIS is able to repeatedly detect small tumors (<3 mm) and tumor-associated changes, whereas CT and US were not routinely capable of detecting pathological developments on this scale.

Adenocarcinoma↗

PubMed2004

Design and implementation of a high frequency electrical impedance tomography system.

Electrical impedance tomography is an imaging modality being investigated for use in detection of breast cancer. Use of higher frequencies than have typically been employed may benefit the detection processes. In this current work we discuss the design and initial implementation of a system having a bandwidth of 10 MHz. Previous investigations into high frequency designs have proven more difficult than anticipated and shown that careful selection of systems architecture is critical to achieving broadband performance above 1 MHz. The design for this new system is based on a digital signal processor (DSP) which is used for control, signal generation and signal processing. Signal generation and detection, software design and preliminary system specifications are discussed.

Breast Neoplasms↗

PubMed2004

Microwave image reconstruction from 3-D fields coupled to 2-D parameter estimation.

An efficient Gauss-Newton iterative imaging technique utilizing a three-dimensional (3-D) field solution coupled to a two-dimensional (2-D) parameter estimation scheme (3-D/2-D) is presented for microwave tomographic imaging in medical applications. While electromagnetic wave propagation is described fully by a 3-D vector field, a 3-D scalar model has been applied to improve the efficiency of the iterative reconstruction process with apparently limited reduction in accuracy. In addition, the image recovery has been restricted to 2-D but is generalizable to three dimensions. Image artifacts related primarily to 3-D effects are reduced when compared with results from an entirely two-dimensional inversion (2-D/2-D). Important advances in terms of improving algorithmic efficiency include use of a block solver for computing the field solutions and application of the dual mesh scheme and adjoint approach for Jacobian construction. Methods which enhance the image quality such as the log-magnitude/unwrapped phase minimization were also applied. Results obtained from synthetic measurement data show that the new 3-D/2-D algorithm consistently outperforms its 2-D/2-D counterpart in terms of reducing the effective imaging slice thickness in both permittivity and conductivity images over a range of inclusion sizes and background medium contrasts.

Algorithms↗

PubMed2004

Shear modulus estimation using parallelized partial volumetric reconstruction.

Magnetic resonance elastography can be limited by the computationally intensive nonlinear inversion schemes that are sometimes employed to estimate shear modulus from externally induced internal tissue displacements. Consequently, we have developed a parallelized partial volume reconstruction approach to overcome this limitation. In this paper, we report results from experiments conducted on breast phantoms and human volunteers to validate the proposed technique. More specifically, we demonstrate that computational cost is linearly related to the number of subzones used during image recovery and that both subzone parallelization and partial volume domain reduction decrease execution time accordingly. Importantly, elastograms computed based on the parallelized partial volume technique are not degraded in terms of either image quality or accuracy relative to their full volume counterparts provided that the estimation domain is sufficiently large to negate the effects of boundary conditions. The clinical results presented in this paper are clearly preliminary; however, the parallelized partial volume reconstruction approach performs sufficiently well to warrant more in-depth clinical evaluation.

Breast Neoplasms↗

PubMed2004

Electromagnetic breast imaging: average tissue property values in women with negative clinical findings.

Representative data are provided for three electromagnetic breast imaging techniques-near-infrared spectroscopy, electrical impedance spectroscopy, and microwave imaging spectroscopy-to serve as potential benchmarks for future investigation. The breasts of 23 women without clinical or mammographic findings of disease were imaged in the coronal plane with nonionizing radiation of varying frequencies. Average electromagnetic property values were reconstructed at each frequency on the basis of computational models of light diffusion, current flow, and microwave propagation. Electromagnetic properties were correlated with subject characteristics and between techniques. Each technique yielded information on breast tissue features (eg, conductivity, permittivity, light scattering, and absorption) that had not previously all been measured in the same individuals.

Adult↗

PubMed2004

Analysis of the microvasculature and tissue type ratios in normal vs. benign and malignant breast tissue.

OBJECTIVE: To analyze the microvasculature and tissue type ratios in normal vs. benign and malignant breast tissue to establish a baseline for expected values against which future imaging studies can be benchmarked. STUDY DESIGN: Using computer-assisted techniques on immunostained breast tissue (normal [n = 28], fibrocystic [n = 37], fibroadenomas [n = 19], invasive carcinomas [n = 19]), values were obtained for microvessel density (MVD), mean vessel area (MVA), vessel orientation (shape) and epithelial:stromal ratio (E:S). Measurement reproducibility and the effects of fibroadenoma stromal hyalinization and fibrocystic disease severity were also tested. RESULTS: Value ranges for the 4 diagnostic groups were significantly different (P < .001). For invasive breast carcinomas, E:S and MVD were significantly higher (P < .001) but MVA was smaller as compared to that in fibroadenomas. Peripherally vs. centrally there was no significant difference in MVD, MVA or vessel shape in the neoplasms. Decreases in E:S and MVD correlated with fibroadenoma stromal hyalinization. Increases in E:S and MVA correlated with more severe fibrocystic disease. Correlation coefficients for measurement reproducibility were high across the diagnostic categories. CONCLUSION: This study established a specific, reproducible, computer-assisted technique and baseline of expected values for morphologic criteria in normal, benign and malignant breast tissue that may be used in the future to correlate new breast imaging responses with these underlying biologic properties.

Adult↗

PubMed2003

Interpreting hemoglobin and water concentration, oxygen saturation, and scattering measured in vivo by near-infrared breast tomography.

Near-infrared spectroscopic tomography was used to measure the properties of 24 mammographically normal breasts to quantify whole-breast absorption and scattering spectra and to evaluate which tissue composition characteristics can be determined from these spectra. The absorption spectrum of breast tissue allows quantification of (i) total hemoglobin concentration, (ii) hemoglobin oxygen saturation, and (iii) water concentration, whereas the scattering spectrum provides information about the size and number density of cellular components and structural matrix elements. These property data were tested for correlation to demographic information, including subject age, body mass index, breast size, and radiographic density. Total hemoglobin concentration correlated inversely to body mass index, likely because lower body mass indicates proportionately less fat and more glandular tissue, and glandular tissue contains greater vascularity, hence, more total hemoglobin. Optical scattering was correlated to breast diameter, subject age, and radiographic density. In the radiographic density, fatty breasts had low scattering power and extremely dense breasts had higher values. This observation is consistent with low attenuation of conventional x-rays with fat and higher attenuation in glandular tissues. Optically, fatty tissues have large scatterers leading to a low scattering power, whereas glandular or fibrous tissues have more cellular and collagen-based structures that lead to high scattering power. The study presents correlative data supporting the hypothesis that optical measurements of absorption and scattering can provide physiologically relevant information about breast tissue composition. These breast constituents vary significantly between individuals and can be altered because of changes in breast physiology or pathological state.

Adult↗

PubMed2003

The effects of internal refractive index variation in near-infrared optical tomography: a finite element modelling approach.

Near-infrared (NIR) tomography is a technique used to measure light propagation through tissue and generate images of internal optical property distributions from boundary measurements. Most popular applications have concentrated on female breast imaging, neonatal and adult head imaging, as well as muscle and small animal studies. In most instances a highly scattering medium with a homogeneous refractive index is assumed throughout the imaging domain. Using these assumptions, it is possible to simplify the model to the diffusion approximation. However, biological tissue contains regions of varying optical absorption and scatter, as well as varying refractive index. In this work, we introduce an internal boundary constraint in the finite element method approach to modelling light propagation through tissue that accounts for regions of different refractive indices. We have compared the results to data from a Monte Carlo simulation and show that for a simple two-layered slab model of varying refractive index, the phase of the measured reflectance data is significantly altered by the variation in internal refractive index, whereas the amplitude data are affected only slightly.

Computer Simulation↗

PubMed2003

In vivo near-infrared spectral detection of pressure-induced changes in breast tissue.

A diffuse near-infrared tomography system was used to measure dynamic changes in the absolute optical properties of the human breast that were induced through pressure applied to the tissue surface. Results from five subjects show that absorption and scattering coefficients changed measurably when pressure was increased and that these relative changes correlated with the subjects' body-mass index, indicating that the effect depends on tissue composition. Fitting the absolute absorption and scattering coefficients at six wavelengths to the molar absorption spectra of the three predominant chromophores revealed that both the average total hemoglobin and oxygen saturation increased by 10%, while water concentration decreased by more than 12%. These changes indicate that the pressure-induced variation is likely due to water displacement and vascular volume increase in the region being imaged, for mild application of pressure to the breast. These results suggest that the pressure applied during optical measurements of tissue may alter the tissue physiology, and care should be taken to factor this effect into the design of optical medical instrumentation. In addition, the technique provides a unique approach to measuring tissue elastic changes in vivo in the female breast and may offer a new method for dynamic contrast imaging based on elasto-optical measurements.

Adult↗

PubMed2003

Three-dimensional optical tomography: resolution in small-object imaging.

Near-infrared (NIR) optical tomography provide estimates of the internal distribution of optical absorption and transport scattering from boundary measurement of light propagation within biological tissue. Although this is a truly three-dimensional (3D) imaging problem, most research to date has concentrated on two-dimensional modeling and image reconstruction. More recently, 3D imaging algorithms are demonstrating better estimation of the light propagation within the imaging region and are providing the basis of more accurate image construction algorithms. As 3D methods emerge, it will become increasingly important to evaluate their resolution, contrast, and localization of optical property heterogeneity. We present a concise study of 3D reconstructed resolution of a small, low-contrast, absorbing and scattering anomaly as it is placed in different locations within a cylindrical phantom. The object is an 8-mm-diameter cylinder, which represents a typical small target that needs to be resolved in NIR mammographic imaging. The best resolution and contrast is observed when the object is located near the periphery of the imaging region (12-22 mm from the edge) and is also positioned within the multiple measurement planes, with the most accurate results seen for the scatter image when the anomaly is at 17 mm from the edge. Furthermore, the accuracy of quantitative imaging is increased to almost 100% of the target values when a priori information regarding the internal structure of imaging domain is utilized.

Breast Neoplasms↗