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Biomedical subjects

Xiaochuan Pan

Publications and source records attributed to Xiaochuan Pan.

10 recordsLinked to original sources

A regulatory network underlying idiopathic pulmonary fibrosis.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease in which genetic susceptibility interacts with epithelial, immune, and mesenchymal remodeling. Although the chromosome 11p15.5 locus contains established IPF susceptibility signals near MUC5B and TOLLIP, the broader regulatory architecture of this region remains incompletely resolved. METHODS: We integrated IPF genome-wide association study summary statistics with methylation, expression, and protein quantitative trait loci using summary-data-based Mendelian randomization (SMR). SMR-prioritized candidates were evaluated in independent transcriptomic and methylation cohorts and further contextualized using microRNA, transcription-factor, protein-interaction, machine-learning, single-cell, and spatial transcriptomic analyses. Fibrosis-associated expression patterns were assessed in a bleomycin-induced pulmonary fibrosis rat model. RESULTS: The analyses recovered the established MUC5B and TOLLIP signals and prioritized BRSK2 as a comparatively underexplored candidate supported by eQTL-based SMR and independent molecular evidence. The BRSK2 pQTL association did not pass the HEIDI test and was therefore not interpreted as convergent protein-level genetic evidence. Network analyses linked BRSK2 to cell-cycle, metabolic-stress, and senescence-related programs, while cross-cohort machine learning prioritized FOXA2, CDC25B, and NFE2 as informative network features. Single-cell and spatial analyses localized BRSK2 preferentially to fibroblast and myofibroblast compartments and to regions with greater histological fibrosis severity. In fibrotic rat lungs, BRSK2 expression increased, whereas FOXA2 and CDC25B decreased at the transcript and protein levels. CONCLUSIONS: These findings refine the molecular landscape of the chromosome 11p15.5 IPF susceptibility locus and prioritize BRSK2 as a candidate component of an IPF-associated profibrotic fibroblast state. Its causal contribution, direct regulatory relationships, and therapeutic tractability require targeted mechanistic validation.

Idiopathic Pulmonary Fibrosis↗

An improved reconstruction algorithm for 3-D diffraction tomography using spherical-wave sources.

Diffraction tomography (DT) is an inversion technique that reconstructs the refractive index distribution of a weakly scattering object. In this paper, a novel reconstruction algorithm for three-dimensional diffraction tomography employing spherical-wave sources is mathematically developed and numerically implemented. Our algorithm is numerically robust and is much more computationally efficient than the conventional filtered backpropagation algorithm. Our previously developed algorithm for DT using plane-wave sources is contained as a special case.

Computer Simulation↗

Image reconstruction with shift-variant filtration and its implication for noise and resolution properties in fan-beam computed tomography.

In computed tomography (CT), the fan-beam filtered backprojection (FFBP) algorithm is used widely for image reconstruction. It is known that the FFBP algorithm can significantly amplify data noise and aliasing artifacts in situations where the focal lengths are comparable to or smaller than the size of the field of measurement (FOM). In this work, we propose an algorithm that is less susceptible to data noise, aliasing, and other data inconsistencies than is the FFBP algorithm while retaining the favorable resolution properties of the FFBP algorithm. In an attempt to evaluate the noise properties in reconstructed images, we derive analytic expressions for image variances obtained by use of the FFBP algorithm and the proposed algorithm. Computer simulation studies are conducted for quantitative evaluation of the spatial resolution and noise properties of images reconstructed by use of the algorithms. Numerical results of these studies confirm the favorable spatial resolution and noise properties of the proposed algorithm and verify the validity of the theoretically predicted image variances. The proposed algorithm and the derived analytic expressions for image variances can have practical implications for both estimation and detection/classification tasks making use of CT images, and they can readily be generalized to other fan-beam geometries.

Algorithms↗

Pitch dependence of longitudinal sampling and aliasing effects in multi-slice helical computed tomography (CT).

In this work, we investigate longitudinal sampling and aliasing effects in multi-slice helical CT. We demonstrate that longitudinal aliasing can be a significant, complicated, and potentially detrimental effect in multi-slice helical CT reconstructions. Multi-slice helical CT scans are generally undersampled longitudinally for all pitches of clinical interest, and the resulting aliasing effects are spatially variant. As in the single-slice case, aliasing is shown to be negligible at the isocentre for circularly symmetric objects due to a fortuitous aliasing cancellation phenomenon. However, away from the isocentre, aliasing effects can be significant, spatially variant, and highly pitch dependent. This implies that measures more sophisticated than isocentre slice sensitivity profiles are needed to characterize longitudinal properties of multi-slice helical CT systems. Such measures are particularly important in assessing the question of whether there are preferred pitches in helical CT. Previous analyses have generally focused only on isocentre sampling patterns, and our more global analysis leads to somewhat different conclusions than have been reached before, suggesting that pitches 3, 4, 5, and 6 are favourable, and that half-integer pitches are somewhat suboptimal.

Artifacts↗

Short-scan SPECT imaging with non-uniform attenuation and 3D distance-dependent spatial resolution.

Image quality and quantitative accuracy in single-photon emission computed tomography (SPECT) can be degraded by, e.g., the effects of photon attenuation and finite spatial resolution. It is generally considered that adequate compensation for such effects on SPECT images requires data acquired over 2 pi. Recently, using the existing consistency condition on the data function, Noo and Wagner (2001 Inverse Problems 17 1357-72) have shown analytically that data acquired over only pi can be used to correct completely for the effect of uniform attenuation in SPECT. It remains unknown, however, whether data acquired only over pi in SPECT with non-uniform attenuation and/or 3D distance-dependent spatial resolution (DDSR) contain complete information for accurate image reconstruction. In this work, we develop a heuristic perspective, which is referred to as the potato peeler perspective to show conceptually that data in SPECT with non-uniform attenuation and/or 3D DDSR acquired over 2 pi contain redundant information and that such information can be used to reduce the scanning angle in SPECT. Specifically, we show heuristically that, in SPECT with only non-uniform attenuation, the scanning angle can be reduced from 2 pi to pi and that, in SPECT with both non-uniform attenuation and DDSR with a physically realistic form, the scanning angle can be reduced from 2 pi to pi in a practical sense. We conduct computer simulation studies, and the results from these studies corroborate the observations obtained based upon the heuristic potato peeler perspective.

Algorithms↗

On a limited-view reconstruction problem in diffraction tomography.

Diffraction tomography (DT) is an inversion technique that reconstructs the refractive index distribution of a scattering object. We previously demonstrated that by exploiting the redundant information in the DT data, the scattering object could be exactly reconstructed using measurements taken over the angular range [0, phimin], where pi < phimin < or = 3pi/2. In this paper, we reveal a relationship between the maximum scanning angle and image resolution when a filtered backpropagation (FBPP) reconstruction algorithm is employed for image reconstruction. Based on this observation, we develop short-scan FBPP algorithms that reconstruct a low-pass filtered scattering object from measurements acquired over the angular range [0, phi(c)], where phi(c) < phimin.

Acoustics↗

Anti-aliasing weighting functions for single-slice helical CT.

Spatially variant longitudinal aliasing plagues most volumes reconstructed from single-slice helical computed tomography data, and its presence can degrade resolution and distort image structures. We have recently developed a Fourier-based approach to longitudinal interpolation in helical computed tomography that can, for scans performed at pitch 1 or lower, essentially eliminate this longitudinal aliasing by exploiting a generalization of the Whittaker-Shannon sampling theorem whose conditions are satisfied by the interlaced pairs of direct and complementary longitudinal samples. However, the algorithm is computationally intensive and cannot be pipelined. In this paper, we address this shortcoming by deriving two spatial-domain, projection-data weighting functions that approximate the application of the Fourier-based approach, and preserve its aliasing suppression properties to some degree, while allowing for a pipelined implementation. The first approach, which we call simply 180AA, for anti-aliasing, is a direct spatial-domain approximation of the 180FT approach. The second approach, which we call 180BSP, is based on an approximate generalized interpolation approach making use of B-splines. Studies of aliasing and resolution properties in reconstructions from simulated data indicate that while the 180AA and 180BSP approaches do not perfectly replicate the favorable aliasing suppression and resolution properties of the 180FT approach, they do represent an improvement over the clinically standard 180LI approach on these fronts.

Computer Simulation↗

Longitudinal aliasing in multislice helical computed tomography: sampling and cone-beam effects.

In this study, we examine longitudinal aliasing properties in multislice helical computed tomography (CT) volumes reconstructed under the multiple parallel fanbeam approximation by use of a 180LI-type algorithm. We focus on the differences between the multislice case and the single-slice case, which has been studied previously. Specifically, we examine longitudinal aliasing properties in four-slice scanners for helical pitches 3 and 6, which are sometimes called "preferred" in four-slice helical CT, because it is believed that the effective longitudinal sampling intervals at these pitches are equivalent to those in single-slice helical CT operating at pitches 1 and 2, respectively. While these equivalences have been supported by comparative studies of slice-sensitivity profiles in single- and multislice helical CT, artifacts have been observed in pitch-3 and pitch-6 multislice images that were not evident in their purported single-slice counterparts. We attribute these differences to aliasing arising in the multislice reconstructions that is not present in the single-slice counterparts. We find that the aliasing has two principal origins: sampling effects similar to those in the single-slice case and cone-beam effects. The difference between the multislice, pitch-3 and single-slice, pitch-1 results is attributed to the small cone angle in multislice helical CT, which introduces inconsistencies among the measurements of different detector rows. The difference between multislice, pitch-6 and single-slice, pitch-2 results is attributed to a combination of the cone angle and genuine differences in sampling patterns. It is argued, however, that the lack of strict equivalence with single-slice counterparts does not necessarily undermine the claim that pitches 3 and 6 are "preferred" relative to other pitches in multislice helical CT.

Artifacts↗

Favorable noise uniformity properties of Fourier-based interpolation and reconstruction approaches in single-slice helical computed tomography.

Volumes reconstructed by standard methods from single-slice helical computed tomography (CT) data have been shown to have noise levels that are highly nonuniform relative to those in conventional CT. These noise nonuniformities can affect low-contrast object detectability and have also been identified as the cause of the zebra artifacts that plague maximum intensity projection (MIP) images of such volumes. While these spatially variant noise levels have their root in the peculiarities of the helical scan geometry, there is also a strong dependence on the interpolation and reconstruction algorithms employed. In this paper, we seek to develop image reconstruction strategies that eliminate or reduce, at its source, the nonuniformity of noise levels in helical CT relative to that in conventional CT. We pursue two approaches, independently and in concert. We argue, and verify, that Fourier-based longitudinal interpolation approaches lead to more uniform noise ratios than do the standard 360LI and 180LI approaches. We also demonstrate that a Fourier-based fan-to-parallel rebinning algorithm, used as an alternative to fanbeam filtered backprojection for slice reconstruction, also leads to more uniform noise ratios, even when making use of the 180LI and 360LI interpolation approaches.

Algorithms↗

Effects of constant frequency noise in magnetic resonance imaging with nonuniform k-space sampling.

Magnetic resonance images can be compromised by constant frequency (CF) noise, such as radio frequency (RF) noise. We investigate the effects of CF noise in four imaging methods with non-uniform k-space sampling: single-shot echo-planar imaging (EPI) with sinusoidal readout gradients, phase-encoded echo-planar spectroscopic imaging (EPSI) with sinusoidal readout gradients, projection-reconstruction imaging, and single-shot spiral imaging. The characteristics of the CF artifacts in each imaging method are studied with numerical simulations. CF noise is found to cause artifacts of nonclassic forms in the reconstructed images. Specifically, dashed-line, streak, and spiral patterns of CF noise appear in EPI/EPSI with sinusoidal readout gradients, projection-reconstruction imaging, and spiral imaging, respectively. The analytical expression for dashed-line artifacts is found to be a weighted sum of Bessel functions and is verified with in vivo experiments. The CF artifacts can be removed during post-processing by eliminating the noise spikes in the Fourier domain of the raw data.

Animals↗