[Show abstract][Hide abstract] ABSTRACT: We integrate a small and portable medical x-ray device with mechanical
testing equipment to enable in-situ, non-invasive measurements of a granular
material's response to mechanical loading. We employ an orthopedic C-arm as the
x-ray source and detector to image samples mounted in the materials tester. We
discuss the design of a custom rotation stage, which allows for sample rotation
and tomographic reconstruction under applied compressive stress. We then
discuss the calibration of the system for 3d computed tomography, as well as
the subsequent image reconstruction process. Using this system to reconstruct
packings of 3d-printed particles, we resolve packing features with 0.52 mm
resolution in a (60 mm)$^3$ field of view. By analyzing the performance bounds
of the system, we demonstrate that the reconstructions exhibit only moderate
[Show abstract][Hide abstract] ABSTRACT: Myocardial blood flow (MBF) can be estimated from dynamic contrast enhanced (DCE) cardiac CT acquisitions, leading to quantitative assessment of regional perfusion. The need for low radiation dose and the lack of consensus on MBF estimation methods motivates this study to refine the selection of acquisition protocols and models for CT-derived MBF. DCE cardiac CT acquisitions were simulated for a range of flow states (MBF = 0.5, 1, 2, 3 ml (min g)(-1), cardiac output = 3, 5, 8 L min(-1)). Patient kinetics were generated by a mathematical model of iodine exchange incorporating numerous physiological features including heterogenenous microvascular flow, permeability and capillary contrast gradients. CT acquisitions were simulated for multiple realizations of realistic x-ray flux levels. CT acquisitions that reduce radiation exposure were implemented by varying both temporal sampling (1, 2, and 3 s sampling intervals) and tube currents (140, 70, and 25 mAs). For all acquisitions, we compared three quantitative MBF estimation methods (two-compartment model, an axially-distributed model, and the adiabatic approximation to the tissue homogeneous model) and a qualitative slope-based method. In total, over 11 000 time attenuation curves were used to evaluate MBF estimation in multiple patient and imaging scenarios. After iodine-based beam hardening correction, the slope method consistently underestimated flow by on average 47.5% and the quantitative models provided estimates with less than 6.5% average bias and increasing variance with increasing dose reductions. The three quantitative models performed equally well, offering estimates with essentially identical root mean squared error (RMSE) for matched acquisitions. MBF estimates using the qualitative slope method were inferior in terms of bias and RMSE compared to the quantitative methods. MBF estimate error was equal at matched dose reductions for all quantitative methods and range of techniques evaluated. This suggests that there is no particular advantage between quantitative estimation methods nor to performing dose reduction via tube current reduction compared to temporal sampling reduction. These data are important for optimizing implementation of cardiac dynamic CT in clinical practice and in prospective CT MBF trials.
Physics in Medicine and Biology 03/2014; 59(7):1533-1556. · 2.70 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Purpose: X-ray fluorescence computed tomography (XFCT) is an emerging imaging modality that maps the three-dimensional distribution of elements, generally metals, in ex vivo specimens and potentially in living animals and humans. At present, it is generally performed at synchrotrons, taking advantage of the high flux of monochromatic x rays, but recent work has demonstrated the feasibility of using laboratory-based x-ray tube sources. In this paper, the authors report the development and experimental implementation of two novel imaging geometries for mapping of trace metals in biological samples with ∼50-500 μm spatial resolution.Methods: One of the new imaging approaches involves illuminating and scanning a single slice of the object and imaging each slice's x-ray fluorescent emissions using a position-sensitive detector and a pinhole collimator. The other involves illuminating a single line through the object and imaging the emissions using a position-sensitive detector and a slit collimator. They have implemented both of these using synchrotron radiation at the Advanced Photon Source.Results: The authors show that it is possible to achieve 250 eV energy resolution using an electron multiplying CCD operating in a quasiphoton-counting mode. Doing so allowed them to generate elemental images using both of the novel geometries for imaging of phantoms and, for the second geometry, an osmium-stained zebrafish.Conclusions: The authors have demonstrated the feasibility of these two novel approaches to XFCT imaging. While they use synchrotron radiation in this demonstration, the geometries could readily be translated to laboratory systems based on tube sources.
Medical Physics 06/2013; 40(6):061903. · 2.91 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We demonstrate the use of task-based image-quality metrics to compare various photoacoustic image-reconstruction algorithms, including a method based on the pseudoinverse of the system matrix, simple backprojection, filtered backprojection, and a method based on the Fourier transform. We use a three-dimensional forward model with a linear transducer array to simulate a photoacoustic imaging system. The reconstructed images correspond with two-dimensional slices of the object and are 128×128 pixels. In order to compare the algorithms, we use channelized Hotelling observers that predict the detection ability of human observers. We use two sets of channels: constant Q and difference of Gaussian spatial frequency channels. We look at three tasks, identification of a point source in a uniform background, identification of a 0.5-mm cube in a uniform background, and identification of a point source in a lumpy background. For the lumpy background task, which is the most realistic of the tasks, the method based on the pseudoinverse performs best according to both sets of channels.
Journal of Biomedical Optics 02/2013; 18(2):26009. · 2.88 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Attenuation effects can be significant in photoacoustic tomography since the generated pressure signals are broadband, and ignoring them may lead to image artifacts and blurring. La Rivière et al. [Opt. Lett. 31(6), pp. 781-783, (2006)] had previously derived a method for modeling the attenuation effect and correcting for it in the image reconstruction. This was done by relating the ideal, unattenuated pressure signals to the attenuated pressure signals via an integral operator. We derive an integral operator relating the attenuated pressure signals to the absorbed optical energy for a planar measurement geometry. The matrix operator relating the two quantities is a function of the temporal frequency, attenuation coefficient and the two-dimensional spatial frequency. We perform singular-value decomposition (SVD) of this integral operator to study the problem further. We find that the smallest singular values correspond to wavelet-like eigenvectors in which most of the energy is concentrated at times corresponding to greater depths in tissue. This allows us to characterize the ill-posedness of recovering the absorbed optical energy distribution at different depths in an attenuating medium. This integral equation can be inverted using standard SVD methods, and the initial pressure distribution can be recovered. We conduct simulations and derive an algorithm for image reconstruction using SVD for a planar measurement geometry. We also study the noise and resolution properties of this image-reconstruction method.
Journal of Biomedical Optics 06/2012; 17(6):061204. · 2.88 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We discuss a method for using the pseudoinverse of the system matrix to
perform photoacoustic image reconstruction. In our method, the
regularization levels are set and the pseudoinverse matrices are
calculated just once for all possible objects, so the reconstruction
step consists only of a matrix-vector multiplication, which is very
fast. We expect this method to work well in photoacoustic imaging
because the dominant noise mechanism is usually transducer thermal
noise, which is object independent. We find that this reconstruction
method offers improvements in ideal observer signal-to-noise ratio,
resolution, and the length of streak artifacts compared to standard
[Show abstract][Hide abstract] ABSTRACT: Many different approaches to spectral CT, also called dual-energy CT, are being investigated for clinical use, but there is somewhat of a lack of quantitative metrics for evaluating performance with regard to clinical tasks. In this paper we apply a Hotelling Observer model with signal variability to the task of distinguishing two different contrast materials in a known background. The calculation of the associated Hotelling SNR gives a quantitative description of how well a particular spectral CT system performs. Unlike the detectability studies that are carried out in conventional CT, the inclusion of signal variability is key to applying the Hotelling Observer to dual-energy data. This model could be applied to many tasks that are being studied in clinical trials, such as creating virtual non-contrast images, bone removal, or kidney stone identification. Additionally, the proposed model can be adapted to examine the information loss associated with various dual-energy reconstruction algorithms.
Nuclear Science Symposium and Medical Imaging Conference (NSS/MIC), 2012 IEEE; 01/2012
[Show abstract][Hide abstract] ABSTRACT: Synchrotron-based X-ray imaging is a useful tool in biomedical research because it can nondestructively produce high-resolution, 3D images. In this technique, X-rays impinge upon a thin scintillator and the visible light emission is focused onto a CCD using microscope optics. With this type of detector, sub-micron resolution has been achieved. We have also studied the possibility of extending this detector to have multiple scintillating layers for the purposes of performing spectral microCT with polychromatic sources. When such a multi-layer detector is illuminated by a polychromatic spectrum, the first layer will preferentially stop lower-energy X-rays, and the deeper layers higher-energy X-rays, leading to limited but perfectly registered spectral resolution. This detection setup also has the advantage of efficient use of synchrotron X-rays, short scan times, and the potential adaptation to a bench top system. Here we present some of our preliminary experimental results obtained using a custom multi-layer scintillating detector in conjunction with a color CCD camera. We found that our dual-layer detector does provide a significant amount of spectral separation, which suggests that material decomposition will be possible. This will be useful in identifying the elemental stains in X-ray histology. So far we have only attempted to do the material decomposition in the image domain because it is simpler to implement and does not require very precise calibration data. In the future, we would like to develop a calibration phantom that will enable us to do the decomposition in the sinogram domain. This yields a more quantitatively rigorous decomposition and has the additional advantage of eliminating beam-hardening artifacts caused by the polychromatic spectrum.
Nuclear Science Symposium and Medical Imaging Conference (NSS/MIC), 2012 IEEE; 01/2012
[Show abstract][Hide abstract] ABSTRACT: This paper presents a feasibility study for using two new imaging geometries for synchrotron X-ray fluorescence emission tomography (XFET) applications. In the proposed approaches, the object is illuminated with synchrotron X-ray beams of various cross-sectional dimensions. The resultant fluorescence photons are detected by high-resolution imaging-spectrometers coupled to collimation apertures. To verify the performance benefits of the proposed methods over the conventional line-by-line scanning approach, we have used both Monte Carlo simulations and an analytical system performance index to compare several different imaging geometries. This study has demonstrated that the proposed XFET approach could lead to a greatly improved imaging speed, which is critical for making XFET a practical imaging modality for a wide range of applications.
[Show abstract][Hide abstract] ABSTRACT: Manganese (Mn) is a calcium (Ca) analog that has long been used as a magnetic resonance imaging (MRI) contrast agent for investigating cardiac tissue functionality, for brain mapping and for neuronal tract tracing studies. Recently, we have extended its use to investigate pancreatic β-cells and showed that, in the presence of MnCl(2), glucose-activated pancreatic islets yield significant signal enhancement in T(1)-weigheted MR images. In this study, we exploited for the first time the unique capabilities of X-ray fluorescence microscopy (XFM) to both visualize and quantify the metal in pancreatic β-cells at cellular and subcellular levels. MIN-6 insulinoma cells grown in standard tissue culture conditions had only a trace amount of Mn, 1.14 ± 0.03 × 10(-11)µg/µm(2), homogenously distributed across the cell. Exposure to 2 mM glucose and 50 µM MnCl(2) for 20 min resulted in nonglucose-dependent Mn uptake and the overall cell concentration increased to 8.99 ± 2.69 × 10(-11) µg/µm(2). When cells were activated by incubation in 16 mM glucose in the presence of 50 µM MnCl(2), a significant increase in cytoplasmic Mn was measured, reaching 2.57 ± 1.34 × 10(-10) µg/µm(2). A further rise in intracellular concentration was measured following KCl-induced depolarization, with concentrations totaling 1.25 ± 0.33 × 10(-9) and 4.02 ± 0.71 × 10(-10) µg/µm(2) in the cytoplasm and nuclei, respectively. In both activated conditions Mn was prevalent in the cytoplasm and localized primarily in a perinuclear region, possibly corresponding to the Golgi apparatus and involving the secretory pathway. These data are consistent with our previous MRI findings, confirming that Mn can be used as a functional imaging reporter of pancreatic β-cell activation and also provide a basis for understanding how subcellular localization of Mn will impact MRI contrast.
[Show abstract][Hide abstract] ABSTRACT: Imaging can potentially make a major contribution to the Zebrafish Phenome Project, which will probe the functions of vertebrate genes through the generation and phenotyping of mutants. Imaging of whole animals at different developmental stages through adulthood will be used to infer biological function. Cell resolutions will be required to identify cellular mechanism and to detect a full range of organ effects. Light-based imaging of live zebrafish embryos is practical only up to ∼2 days of development, owing to increasing pigmentation and diminishing tissue lucency with age. The small size of the zebrafish makes possible whole-animal imaging at cell resolutions by histology and micron-scale tomography (microCT). The histological study of larvae is facilitated by the use of arrays, and histology's standard use in the study of human disease enhances its translational value. Synchrotron microCT with X-rays of moderate energy (10-25 keV) is unimpeded by pigmentation or the tissue thicknesses encountered in zebrafish of larval stages and beyond, and is well-suited to detecting phenotypes that may require 3D modeling. The throughput required for this project will require robotic sample preparation and loading, increases in the dimensions and sensitivity of scintillator and CCD chips, increases in computer power, and the development of new approaches to image processing, segmentation, and quantification.
Current opinion in genetics & development 09/2011; 21(5):620-9. · 8.99 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In recent years, the authors and others have been exploring the use of penalized-likelihood sinogram-domain smoothing and restoration approaches for emission and transmission tomography. The motivation for this strategy was initially pragmatic: to provide a more computationally feasible alternative to fully iterative penalized-likelihood image reconstruction involving expensive backprojections and reprojections, while still obtaining some of the benefits of the statistical modeling employed in penalized-likelihood approaches. In this work, the authors seek to compare the two approaches in greater detail.
The sinogram-domain strategy entails estimating the "ideal" line integrals needed for reconstruction of an activity or attenuation distribution from the set of noisy, potentially degraded tomographic measurements by maximizing a penalized-likelihood objective function. The objective function models the data statistics as well as any degradation that can be represented in the sinogram domain. The estimated line integrals can then be input to analytic reconstruction algorithms such as filtered backprojection (FBP). The authors compare this to fully iterative approaches maximizing similar objective functions.
The authors present mathematical analyses based on so-called equivalent optimization problems that establish that the approaches can be made precisely equivalent under certain restrictive conditions. More significantly, by use of resolution-variance tradeoff studies, the authors show that they can yield very similar performance under more relaxed, realistic conditions.
The sinogram- and image-domain approaches are equivalent under certain restrictive conditions and can perform very similarly under more relaxed conditions. The match is particularly good for fully sampled, high-resolution CT geometries. One limitation of the sinogram-domain approach relative to the image-domain approach is the difficulty of imposing additional constraints, such as image non-negativity.
Medical Physics 08/2011; 38(8):4811-23. · 2.91 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Iterative image reconstruction offers improved signal to noise properties for CT imaging. A primary challenge with iterative methods is the substantial computation time. This computation time is even more prohibitive in 4D imaging applications, such as cardiac gated or dynamic acquisition sequences. In this work, we propose only updating the time-varying elements of a 4D image sequence while constraining the static elements to be fixed or slowly varying in time. We test the method with simulations of 4D acquisitions based on measured cardiac patient data from a) a retrospective cardiac-gated CT acquisition and b) a dynamic perfusion CT acquisition. We target the kinetic elements with one of two methods: 1) position a circular ROI on the heart, assuming area outside ROI is essentially static throughout imaging time; and 2) select varying elements from the coefficient of variation image formed from fast analytic reconstruction of all time frames. Targeted kinetic elements are updated with each iteration, while static elements remain fixed at initial image values formed from the reconstruction of data from all time frames. Results confirm that the computation time is proportional to the number of targeted elements; our simulations suggest that 3 times reductions in reconstruction time. The images reconstructed with the proposed method have matched mean square error with full 4D reconstruction. The proposed method is amenable to most optimization algorithms and offers the potential for significant computation improvements, which could be traded off for more sophisticated system models or penalty terms.
[Show abstract][Hide abstract] ABSTRACT: We compare imaging systems using continuous-wave (CW) lasers with a chirped intensity modulation frequency to pulsed lasers. We show that the resolution is the same in both cases. We also compare the signal-to-noise ratio (SNR) of the two systems assuming the fluence is set by the American National Standards Institute (ANSI) limits. Although the SNR depends on several parameters, we find that it is about 20 dB to 30 dB larger for pulsed lasers for reasonable values of the parameters. However, CW diode lasers have the advantage of being compact and relatively inexpensive, which may outweigh the slightly lower SNR in many applications.
[Show abstract][Hide abstract] ABSTRACT: With the goal of producing a less computationally intensive alternative to fully-iterative penalized-likelihood image reconstruction, our group has been exploring the use of penalized-likelihood sinogram restoration for transmission tomography. Sinogram restoration allows for the correction of anode angle effects, off-focal radiation, detector afterglow, crosstalk, beam hardening, and noise effects without the backprojections and reprojections used in fully-iterative reconstruction methods. After sinogram restoration, reconstruction is performed using traditional filtered backprojection methods. Previously, we have exclusively used a quadratic penalty in our restoration objective function. Here, we derive a restoration update equation using separable parabolic surrogates (SPS) for non-quadratic penalties. Using the edge-preserving Huber penalty in our sinogram restoration, we show improvements in resolution-variance tradeoffs compared to using a quadratic penalty in the sinogram restoration. However, this simple approach to edge preservation in the sinogram domain is affected by the physical size of the edge and not just the increase in contrast across the edge. This is a disadvantage relative to image-domain edge-preserving methods.
Nuclear Science Symposium and Medical Imaging Conference (NSS/MIC), 2011 IEEE; 01/2011
[Show abstract][Hide abstract] ABSTRACT: In this paper, the feasibility of differentiating contrast agents in a water background using multiple-energy micro-CT based on the setup described was examined.
Nuclear Science Symposium and Medical Imaging Conference (NSS/MIC), 2011 IEEE; 01/2011
[Show abstract][Hide abstract] ABSTRACT: Several papers have recently addressed the issue of estimating chromophore concentration in optoacoustic imaging (OAI) using multiple wavelengths. The choice of wavelengths obviously affects the accuracy and precision of the estimates. One might assume that the wavelengths that maximize the extinction coefficients of the chromophores would be the most suitable. However, this may not always be the case since the distribution of light intensity in the medium is also wavelength dependent. In this paper, we explore a method for optimizing the choice of wavelengths based on the Cramer-Rao lower bound (CRLB) on the variance of the chromophore concentration. This lower bound on variance can be evaluated numerically for different wavelengths using the variation of the extinction coefficients and scattering coefficients with wavelength. The wavelengths that give the smallest variance will be considered optimal for multi-wavelength OAI to estimate the chromophore concentrations. The expression for the CRLB has been derived analytically for estimating the concentration of multiple chromophores for several simple phantom models for the case when the optoacoustic signal is proportional to the product of the optical absorption and the illumination function. This approach could be easily extended to other geometries.
Physics in Medicine and Biology 12/2010; 55(23):7231-51. · 2.70 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A CT scanner measures the energy that is deposited in each channel of a detector array by x rays that have been partially absorbed on their way through the object. The measurement process is complex and quantitative measurements are always and inevitably associated with errors, so CT data must be preprocessed prior to reconstruction. In recent years, the authors have formulated CT sinogram preprocessing as a statistical restoration problem in which the goal is to obtain the best estimate of the line integrals needed for reconstruction from the set of noisy, degraded measurements. The authors have explored both penalized Poisson likelihood (PL) and penalized weighted least-squares (PWLS) objective functions. At low doses, the authors found that the PL approach outperforms PWLS in terms of resolution-noise tradeoffs, but at standard doses they perform similarly. The PWLS objective function, being quadratic, is more amenable to computational acceleration than the PL objective. In this work, the authors develop and compare two different methods for implementing PWLS sinogram restoration with the hope of improving computational performance relative to PL in the standard-dose regime. Sinogram restoration is still significant in the standard-dose regime since it can still outperform standard approaches and it allows for correction of effects that are not usually modeled in standard CT preprocessing.
The authors have explored and compared two implementation strategies for PWLS sinogram restoration: (1) A direct matrix-inversion strategy based on the closed-form solution to the PWLS optimization problem and (2) an iterative approach based on the conjugate-gradient algorithm. Obtaining optimal performance from each strategy required modifying the naive off-the-shelf implementations of the algorithms to exploit the particular symmetry and sparseness of the sinogram-restoration problem. For the closed-form approach, the authors subdivided the large matrix inversion into smaller coupled problems and exploited sparseness to minimize matrix operations. For the conjugate-gradient approach, the authors exploited sparseness and preconditioned the problem to speed up convergence.
All methods produced qualitatively and quantitatively similar images as measured by resolution-variance tradeoffs and difference images. Despite the acceleration strategies, the direct matrix-inversion approach was found to be uncompetitive with iterative approaches, with a computational burden higher by an order of magnitude or more. The iterative conjugate-gradient approach, however, does appear promising, with computation times half that of the authors' previous penalized-likelihood implementation.
Iterative conjugate-gradient based PWLS sinogram restoration with careful matrix optimizations has computational advantages over direct matrix PWLS inversion and over penalized-likelihood sinogram restoration and can be considered a good alternative in standard-dose regimes.
Medical Physics 11/2010; 37(11):5929-38. · 2.91 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: This paper presents a feasibility study of using emission tomography
(ET) systems for synchrotron X-ray fluorescence computer tomography
(XFCT). The proposed detection system combines high-resolution
semiconductor detectors with multiple-pinhole apertures. The key
advantage of using an ET-based detection system is that 3D distributions
of trace elements can be built up with much reduced scanning motion and
potentially without need for tomographic reconstruction. In comparison
to the conventional line-by-line scanning scheme, the ET-based imaging
system allows a great reduction in imaging time, which has been one of
the major hurdles for current XFCT studies. In order to compare
different imaging schemes for XFCT studies, we developed an analytical
performance index that is based on the fundamental tradeoffs between
image noise and spatial resolution achievable with given detection
configurations. To further demonstrate the feasibility of using SPECT
apertures for XFCT, a prototype CCD-based multiple-pinhole imaging
system was set up at the Advanced Photon Source (APS) for imaging
phantoms that contain solutions of several trace metals. Simultaneously
acquired 3D distributions of these elements are presented.
[Show abstract][Hide abstract] ABSTRACT: We are creating a state-of-the-art 2D and 3D imaging atlas of zebrafish
development. The atlas employs both 2D histology slides and 3D benchtop
and synchrotron micro CT results. Through this atlas, we expect to
document normal and abnormal organogenesis, to reveal new levels of
structural detail, and to advance image informatics as a form of systems
biology. The zebrafish has become a widely used model organism in
biological and biomedical research for studies of vertebrate development
and gene function. In this work, we will report on efforts to optimize
synchrotron microCT imaging parameters for zebrafish at crucial
developmental stages. The aim of these studies is to establish protocols
for high-throughput phenotyping of normal, mutant and diseased
zebrafish. We have developed staining and embedding protocols using
different heavy metal stains (osmium tetroxide and uranyl acetate) and
different embedding media (Embed 812 and glycol methacrylate). We have
explored the use of edge subtraction and multi-energy techniques for
contrast enhancement and we have examined the use of different
sample-detector distances with unstained samples to explore and optimize
phase-contrast enhancement effects. We will report principally on our
efforts to optimize energy choice for single- and multi-energy studies
as well as our efforts to optimize the degree of phase contrast