Hongwei Ye

Development of ultrafast laser-based x-ray in-vivo phase-contrast micro-CT beamline for biomedical applications at Advanced Laser Light Source (ALLS)

We are developing and exploring the imaging performance of, an in vivo, in-line holography, x-ray phase-contrast, micro-CT system with an ultrafast laser-based x-ray (ULX) source. By testing and refining our system, and by performing computer simulations, we plan to improve system performance in terms of contrast resolution and multi-energy imaging to a level beyond what can be obtained using a conventional microfocal x-ray tube. Initial CT projection sets at single energy (Mo Kα and Kβ lines) were acquired in the Fresnel regime and reconstructed for phantoms and a euthanized mouse. We also performed computer simulations of phase-contrast micro-CT scans for low-contrast, soft-tissue, tumor imaging. We determined that, in order to perform a phase-contrast, complete micro-CT scan using ULX, the following conditions must be met: (i) the x-ray source needs to be stable during the scan; (ii) the laser focal spot size needs to be less than 10 μm for source-to-object distance greater than 30 cm; (iii) the laser light intensity on the target needs to be in the range of 5 × 1017 to 5 × 1019 W/cm2; (iv) the ablation protection system needs to allow uninterrupted scans; (v) the laser light focusing on the target needs to remain accurate during the entire scan; (vi) a fresh surface of the target must be exposed to consecutive laser shots during the entire scan; (vii) the effective detector element size must be less than 12 μm. Based on the results obtained in this research project, we anticipate that the new 10 Hz, 200 TW laser with 50W average power that is being commissioned at ALLS will allow us practical implementation of in vivo x-ray phase-contrast micro-CT.

Soft tissue small avascular tumor imaging with x-ray phase-contrast micro-CT in-line holography

To assess the feasibility of small soft tissue avascular tumor micro-CT imaging with x-ray phase-contrast in-line holography, we have studied micro-CT imaging with in-line geometry of small spheroidal avascular tumor models with quiescent cell core (< 250 μm) and various distributions of the proliferating cell density (PCD) forming the outer shell. We have simulated imaging with an ultrafast laser-based x-ray source with a Mo target. We observe phase-contrast enhancement of the tumor boundaries in the reconstructed transaxial images, resulting in improved detection of small soft tissue tumors, providing that the PCD density gradient is sufficiently large.

Implementation of strip-area system model for fan-beam collimator SPECT reconstruction

We have implemented a more accurate physical system representation, a strip-area system model (SASM), for improved fan-beam collimator (FBC) SPECT reconstruction. This approach required implementation of modified ray tracing and attenuation compensation in comparison to a line-length system model (LLSM). We have compared performance of SASM with LLSM using Monte Carlo and analytical simulations of FBC SPECT from a thorax phantom. OSEM reconstruction was performed with OS=3 in a 64×64 matrix with attenuation compensation (assuming uniform attenuation of 0.13 cm-1). Scatter correction and smoothing were not applied. We observe overall improvement in SPECT image bias, visual image quality and an improved hot myocardium contrast for SASM vs. LLSM. In contrast to LLSM, the sensitivity pattern artifacts are not present in the SASM reconstruction. In both reconstruction methods, cross-talk image artifacts (e.g. inverse images of the lungs) can be observed, due to the uniform attenuation map used. SASM applied to fan-beam collimator SPECT results in better image quality and improved hot target contrast, as compared to LLSM, but at the expense of 1.5-fold increase in reconstruction time.

Mean absorbed dose to mouse in micro-CT imaging with an ultrafast laser-based x-ray source

We have investigated theoretically the mean absorbed dose to the mouse in our newly constructed, in-line holography, x-ray phase-contrast, in-vivo, micro-CT system with an ultrafast laser-based x-ray (ULX) source. We assumed that the effective mouse diameter was 30 mm and the x-ray detector required minimum 30 μGy per frame to produce high quality images. The following laser target-filter combinations were considered: Ag-Ag, Mo-Mo, Sn- Sn. In addition, we considered narrow-pass multilayer x-ray mirrors. The corresponding ULX spectra were obtained using a CZT solid-state spectrometer. The approach used for dose computation was similar to human dose estimation. The mouse was modeled as a tissue-equivalent cylinder located at the isocenter with diameter 30 mm and density 1g/cm3. A layer of dermis (skin and fur) with 1 mm thickness was also modeled. Imparted energy per volume was estimated for 1 keV wide x-ray energy intervals in the 6-100 keV range. Monte Carlo simulations were performed using the SIERRA code previously validated using 30 mm diameter PMMA phantom. The results obtained indicate that: a) the mean absorbed dose for ULX is less than or equal to that from a W-anode micro-CT tube operating at 30-40 kVp with 0.5 or 1.0 mm Al; b) for filter thickness above 100 μm, Sn-Sn results in the highest dose, followed by Ag-Ag and Mo-Mo; c) the multilayer x-ray mirror with FWHM ≤ 10 keV produces significantly lower dose than metallic foil filters. We conclude that ULX can provide better dose utilization than a microfocal x-ray tube for in vivo microtomography applications.

Implementation of a fully 3D system model for brain SPECT with fan-beam-collimator OSEM reconstruction with 3D total variation regularization

In order to improve tomographically reconstructed image quality, we have implemented a fully 3D reconstruction, using an ordered subsets expectation maximization (OSEM) algorithm for fan-beam collimator (FBC) SPECT, along with a volumetric system model-fan-volume system model (FVSM), a modified attenuation compensation, a 3D depth- and angle-dependent resolution and sensitivity correction, and a 3D total variation (TV) regularization. SPECT data were acquired in a 128x64 matrix, in 120 views with a circular orbit. The numerical Zubal brain phantom was used to simulate a FBC HMPAO Tc-99m brain SPECT scan, and a low noise and scatter-free projection dataset was obtained using the SimSET Monte Carlo package. A SPECT scan for a mini-Defrise phantom and brain HMPAO SPECT scans for five patients were acquired with a triple-head gamma camera (Triad 88) equipped with a low-energy high-resolution (LEHR) FBC. The reconstructed images, obtained using clinical filtered back projection (FBP), OSEM with a line-length system model (LLSM) and 3D TV regularization, and OSEM with FVSM and 3D TV regularization were quantitatively studied. Overall improvement in the image quality has been observed, including better axial and transaxial resolution, better integral uniformity, higher contrast-to-noise ration between the gray matter and the white matter, and better accuracy and lower bias in OSEM-FVSM, compared with OSEM-LLSM and clinical FBP.

Expectation maximization SPECT reconstruction with a content-adaptive singularity-based mesh-domain image model

To improve the speed and quality of ordered-subsets expectation-maximization (OSEM) SPECT reconstruction, we have implemented a content-adaptive, singularity-based, mesh-domain, image model (CASMIM) with an accurate algorithm for estimation of the mesh-domain system matrix. A preliminary image, used to initialize CASMIM reconstruction, was obtained using pixel-domain OSEM. The mesh-domain representation of the image was produced by a 2D wavelet transform followed by Delaunay triangulation to obtain joint estimation of nodal locations and their activity values. A system matrix with attenuation compensation was investigated. Digital chest phantom SPECT was simulated and reconstructed. The quality of images reconstructed with OSEM-CASMIM is comparable to that from pixel-domain OSEM, but images are obtained five times faster by the CASMIM method.

Development of a fully 3D system model in iterative expectation-maximization reconstruction for cone-beam SPECT

In order to improve reconstructed image quality for cone-beam collimator SPECT, we have developed and implemented a fully 3D reconstruction, using an ordered subsets expectation maximization (OSEM) algorithm, along with a volumetric system model - cone-volume system model (CVSM), a modified attenuation compensation, and a 3D depth- and angle-dependent resolution and sensitivity correction. SPECT data were acquired in a 128×128 matrix, in 120 views with a single circular orbit. Two sets of numerical Defrise phantoms were used to simulate CBC SPECT scans, and low noise and scatter-free projection datasets were obtained using the SimSET Monte Carlo package. The reconstructed images, obtained using OSEM with a line-length system model (LLSM) and a 3D Gaussian post-filter, and OSEM with FVSM and a 3D Gaussian post-filter were quantitatively studied. Overall improvement in the image quality has been observed, including better transaxial resolution, higher contrast-to-noise ratio between hot and cold disks, and better accuracy and lower bias in OSEM-CVSM, compared with OSEM-LLSM.

Implementation of a fully 3D iterative reconstruction of combined parallel- and cone-beam collimator SPELT

To improve contrast-to-noise ratio in a small volume of interest, a combination of parallel- and cone-beam collimator SPECT acquisition and fully 3D iterative reconstruction with a volumetric system model has been developed. The Monte Carlo package SimSET along with a numerical chest phantom with half-ring defect were used to simulate static cardiac SPECT scans. Parallel-beam only, cone-beam only, Jaszczak approach, and our proposed parallel-cone approach were applied in reconstruction. The visual quality of the Jaszczak method and the proposed parallel-cone reconstruction is much better than cone-only reconstruction, and is free of truncation artifacts. Contrast- to-noise ratio, noise, and bias in a small volume-of-interest encompassing the heart have been improved in the proposed parallel- and cone-beam approach, as compared to the other three methods.

A practical correction of scatter-related artifacts in SPECT reconstruction

We have observed that an expectation maximization (EM) algorithm applied to SPECT reconstruction may produce hotspot artifacts of varying intensity. Our hypothesis was that scatter caused these artifacts. To test this assumption, we studied the performance of forward- and back-projection procedures in the EM algorithm for simulated and experimental SPECT data. First, synthetic scatter-free projections and projections with only one scattered photon in each view were created for a simulated simple object, and reconstructed with a fully 3D ordered-subsets EM (OSEM) algorithm. Then, Monte Carlo simulated brain SPECT (with no scatter and with scatter present), a mini-Defrise phantom, and patient SPECT were reconstructed. We confirmed our hypothesis: hot-spot artifacts appeared only in the reconstruction from noisy projections but not in the reconstruction from scatter-free projections. We investigated a practical and simple method, critical path-length control (CPLC), for suppression of the hot-spot artifacts. To this end we performed reconstructions with or without CPLC and quantitatively evaluated the results including estimation of accuracy, bias, contrast-to-noise ratio, and uniformity. We found that the OSEM-with-CPLC method significantly reduced hot-spot artifacts, and yielded a similar or improved image quality. We conclude that the CPLC method provides a useful yet simple tool to reduce scatter-related hot-spot artifacts.