Bert Vandeghinste

Iterative CT Reconstruction Using Shearlet-Based Regularization

Total variation (TV) methods have been proposed to improve the image quality in count-reduced images, by reducing the variation between neighboring pixels. Although very easy to implement and fast to compute, TV-based methods may lead to a loss of texture information when applied to images with complex textures, such as high-resolution abdominal CT images. Here, we investigate the use of another regularization approach in the context of medical images based on multiresolution transformations. One such transformation is the shearlet transform, which is optimally sparse for images that are C2 except for discontinuities along C2 curves, and has better directional sensitivity than most other, related, wavelet transform approaches. We propose to solve the convex problem using the split-Bregman (augmented Lagrangian) approach. One of the primary advantages of the split-Bregman approach, is that the shearlet transform can easily be incorporated into the sparse-view CT reconstruction. The required sparsity prior is the l1 norm of the shearlet coefficients. Results are shown for this method in comparison to the same framework with TV as the regularization term on simulated data. The noise-resolution performance is investigated at different contrast levels. At equal image noise, TV-based regularization outperforms shearlet-based regularization. However, when image texture is analyzed on measured mouse data, shearlets outperform TV, which suffers from staircasing effects. Our results show that there are benefits in using shearlets in CT imaging: texture is reconstructed more accurately compared to when TV is used, without biasing the image towards a piecewise constant image model. However, due to the larger support of the basis functions, our results suggest that uncareful usage of shearlets may lead to wavy artifacts, which can be equally unwanted as staircasing effects.

Replacing Vascular Corrosion Casting by In Vivo Micro-CT Imaging for Building 3D Cardiovascular Models in Mice

PurposeThe purpose of this study was to investigate if in vivo micro-computed tomography (CT) is a reliable alternative to micro-CT scanning of a vascular corrosion cast. This would allow one to study the early development of cardiovascular diseases.ProceduresDatasets using both modalities were acquired, segmented, and used to generate a 3D geometrical model from nine mice. As blood pool contrast agent, Fenestra VC-131 was used. Batson’s No. 17 was used as casting agent. Computational fluid dynamics simulations were performed on both datasets to quantify the difference in wall shear stress (WSS).ResultsAortic arch diameters show 30% to 40% difference between the Fenestra VC-131 and the casted dataset. The aortic arch bifurcation angles show less than 20% difference between both datasets. Numerically computed WSS showed a 28% difference between both datasets.ConclusionsOur results indicate that in vivo micro-CT imaging can provide an excellent alternative for vascular corrosion casting. This enables follow-up studies.

Kinetics of angiogenic changes in a new mouse model for hepatocellular carcinoma

BackgroundThe increasing incidence of hepatocellular carcinoma in Western countries has led to an expanding interest of scientific research in this field. Therefore, a vast need of experimental models that mimic the natural pathogenesis of hepatocellular carcinoma (HCC) in a short time period is present. The goal of our study was (1) to develop an efficient mouse model for HCC research, in which tumours develop in a natural background of fibrosis and (2) to assess the time-dependent angiogenic changes in the pathogenesis of HCC.MethodsWeekly intraperitoneal injections with the hepatocarcinogenic compound N-nitrosodiethylamine was applied as induction method and samples were taken at several time points to assess the angiogenic changes during the progression of HCC.ResultsThe N-nitrosodiethylamine-induced mouse model provides well vascularised orthotopic tumours after 25 weeks. It is a representative model for human HCC and can serve as an excellent platform for the development of new therapeutic targets.

Design and performance of a compact and stationary microSPECT system.

PURPOSE Over the last ten years, there has been an extensive growth in the development of microSPECT imagers. Most of the systems are based on the combination of conventional, relatively large gamma cameras with poor intrinsic spatial resolution and multipinhole collimators working in large magnification mode. Spatial resolutions range from 0.58 to 0.76 mm while peak sensitivities vary from 0.06% to 0.4%. While pushing the limits of performance is of major importance, the authors believe that there is a need for smaller and less complex systems that bring along a reduced cost. While low footprint and low-cost systems can make microSPECT available to more researchers, the ease of operation and calibration and low maintenance cost are additional factors that can facilitate the use of microSPECT in molecular imaging. In this paper, the authors simulate the performance of a microSPECT imager that combines high space-bandwidth detectors and pinholes with truncated projection, resulting in a small and stationary system. METHODS A system optimization algorithm is used to determine the optimal SPECT systems, given our high resolutions detectors and a fixed field-of-view. These optimal system geometries are then used to simulate a Defrise disk phantom and a hot rod phantom. Finally, a MOBY mouse phantom, with realistic concentrations of Tc99m-tetrofosmin is simulated. RESULTS Results show that the authors can successfully reconstruct a Defrise disk phantom of 24 mm in diameter without any rotating system components or translation of the object. Reconstructed spatial resolution is approximately 800 μm while the peak sensitivity is 0.23%. Finally, the simulation of the MOBY mouse phantom shows that the authors can accurately reconstruct mouse images. CONCLUSIONS These results show that pinholes with truncated projections can be used in small magnification or minification mode to obtain a compact and stationary microSPECT system. The authors showed that they can reach state-of-the-art system performance and can successfully reconstruct images with realistic noise levels in a preclinical context. Such a system can be useful for dynamic SPECT imaging.

Iterative CT reconstruction using shearlet-based regularization

In computerized tomography, it is important to reduce the image noise without increasing the acquisition dose. Extensive research has been done into total variation minimization for image denoising and sparse-view reconstruction. However, TV minimization methods show superior denoising performance for simple images (with little texture), but result in texture information loss when applied to more complex images. Since in medical imaging, we are often confronted with textured images, it might not be beneficial to use TV. Our objective is to find a regularization term outperforming TV for sparse-view reconstruction and image denoising in general. A recent efficient solver was developed for convex problems, based on a split-Bregman approach, able to incorporate regularization terms different from TV. In this work, a proof-of-concept study demonstrates the usage of the discrete shearlet transform as a sparsifying transform within this solver for CT reconstructions. In particular, the regularization term is the 1-norm of the shearlet coefficients. We compared our newly developed shearlet approach to traditional TV on both sparse-view and on low-count simulated and measured preclinical data. Shearlet-based regularization does not outperform TV-based regularization for all datasets. Reconstructed images exhibit small aliasing artifacts in sparse-view reconstruction problems, but show no staircasing effect. This results in a slightly higher resolution than with TV-based regularization.

Use of a ray-based reconstruction algorithm to accurately quantify preclinical microSPECT images

This work aimed to measure the in vivo quantification errors obtained when ray-based iterative reconstruction is used in micro-single-photon emission computed tomography (SPECT). This was investigated with an extensive phantom-based evaluation and two typical in vivo studies using 99mTc and 111In, measured on a commercially available cadmium zinc telluride (CZT)-based small-animal scanner. Iterative reconstruction was implemented on the GPU using ray tracing, including (1) scatter correction, (2) computed tomography-based attenuation correction, (3) resolution recovery, and (4) edge-preserving smoothing. It was validated using a National Electrical Manufacturers Association (NEMA) phantom. The in vivo quantification error was determined for two radiotracers: [99mTc]DMSA in naive mice (n = 10 kidneys) and [111In]octreotide in mice (n = 6) inoculated with a xenograft neuroendocrine tumor (NCI-H727). The measured energy resolution is 5.3% for 140.51 keV (99mTc), 4.8% for 171.30 keV, and 3.3% for 245.39 keV (111In). For 99mTc, an uncorrected quantification error of 28 ± 3% is reduced to 8 ± 3%. For 111In, the error reduces from 26 ± 14% to 6 ± 22%. The in vivo error obtained with “mTc-dimercaptosuccinic acid ([99mTc]DMSA) is reduced from 16.2 ± 2.8% to −0.3 ± 2.1% and from 16.7 ± 10.1% to 2.2 ± 10.6% with [111In]octreotide. Absolute quantitative in vivo SPECT is possible without explicit system matrix measurements. An absolute in vivo quantification error smaller than 5% was achieved and exemplified for both [”mTc]DMSA and [111In]octreotide.

FlexiSPECT: A SPECT System Consisting of a Compact High-Resolution Scintillation Detector (SPECTatress) and a Lofthole Collimator

This article describes a compact single-photon emission computed tomography (SPECT) system that consists of a high-resolution detector combined with a lofthole collimator. The detector is based on a NaI(Tl) scintillator, a position sensitive photomultiplier (PSPMT), dedicated read-out electronics that digitize all PSPMT anodes and finally, a maximum likelihood algorithm for position estimation. The collimator has a new pinhole geometry, called the lofthole. Our choice of magnification (1.06 for the mouse setup, 0.63 for the rat setup) results in a small system with a footprint of 45 cm × 25 cm. Design and measurements of both the detector and the SPECT system are shown. Detector measurements with a beam source have been done to investigate the spatial and energy resolution of the detector. Two SPECT setups have been made, one that fits rat-size phantoms and one that fits mouse-size phantoms. On both setups we have done measurements of a Derenzo phantom and a uniformity phantom. The results show that the detector resolution is 1.1 mm and energy resolution is 9.3% in the center of the detector. With the tomographic rat setup we are able to distinguish the 2.4 mm hot rods in a Derenzo phantom. The mouse setup allows us to distinguish the 1.6 mm rods. This demonstrates the SPECT capabilities of this compact prototype scanner.

Vulnerable Plaque Detection and Quantification with Gold Particle-Enhanced Computed Tomography in Atherosclerotic Mouse Models

Recently, an apolipoprotein E-deficient (ApoE-/-) mouse model with a mutation (C1039G+/-) in the fibrillin-1 (Fbn1) gene (ApoE-/-Fbn1C1039G+/- mouse model) was developed showing vulnerable atherosclerotic plaques, prone to rupture, in contrast to the ApoE-/- mouse model, where mainly stable plaques are present. One indicator of plaque vulnerability is the level of macrophage infiltration. Therefore, this study aimed to measure and quantify in vivo the macrophage infiltration related to plaque development and progression. For this purpose, 5-weekly consecutive gold nanoparticle-enhanced micro-computed tomography (microCT) scans were acquired. Histology confirmed that the presence of contrast agent coincided with the presence of macrophages. Based on the microCT scans, regions of the artery wall with contrast agent present were calculated and visualized in three dimensions. From this information, the contrast-enhanced area and contrast-enhanced centerline length were calculated for the branches of the carotid bifurcation (common, external, and internal carotid arteries). Statistical analysis showed a more rapid development and a larger extent of plaques in the ApoE-/-Fbn1C1039G+/- compared to the ApoE-/- mice. Regional differences between the branches were also observable and quantifiable. We developed and applied a methodology based on gold particle-enhanced microCT to visualize the presence of macrophages in atherosclerotic plaques in vivo.Recently, an apolipoprotein E–deficient (ApoE−/−) mouse model with a mutation (C1039G+/−) in the fibrillin-1 (Fbn1) gene (ApoE−/−Fbn1C1039G+/− mouse model) was developed showing vulnerable atherosclerotic plaques, prone to rupture, in contrast to the ApoE−/− mouse model, where mainly stable plaques are present. One indicator of plaque vulnerability is the level of macrophage infiltration. Therefore, this study aimed to measure and quantify in vivo the macrophage infiltration related to plaque development and progression. For this purpose, 5-weekly consecutive gold nanoparticle–enhanced micro–computed tomography (microCT) scans were acquired. Histology confirmed that the presence of contrast agent coincided with the presence of macrophages. Based on the microCT scans, regions of the artery wall with contrast agent present were calculated and visualized in three dimensions. From this information, the contrast-enhanced area and contrast-enhanced centerline length were calculated for the branches of the carotid bifurcation (common, external, and internal carotid arteries). Statistical analysis showed a more rapid development and a larger extent of plaques in the ApoE−/−Fbn1C1039G+/− compared to the ApoE−/− mice. Regional differences between the branches were also observable and quantifiable. We developed and applied a methodology based on gold particle–enhanced microCT to visualize the presence of macrophages in atherosclerotic plaques in vivo.

Low-dose micro-CT imaging for vascular segmentation and analysis using sparse-view acquisitions.

The aim of this study is to investigate whether reliable and accurate 3D geometrical models of the murine aortic arch can be constructed from sparse-view data in vivo micro-CT acquisitions. This would considerably reduce acquisition time and X-ray dose. In vivo contrast-enhanced micro-CT datasets were reconstructed using a conventional filtered back projection algorithm (FDK), the image space reconstruction algorithm (ISRA) and total variation regularized ISRA (ISRA-TV). The reconstructed images were then semi-automatically segmented. Segmentations of high- and low-dose protocols were compared and evaluated based on voxel classification, 3D model diameters and centerline differences. FDK reconstruction does not lead to accurate segmentation in the case of low-view acquisitions. ISRA manages accurate segmentation with 1024 or more projection views. ISRA-TV needs a minimum of 256 views. These results indicate that accurate vascular models can be obtained from micro-CT scans with 8 times less X-ray dose and acquisition time, as long as regularized iterative reconstruction is used.

Absence of cardiovascular manifestations in a haploinsufficient Tgfbr1 mouse model

Loeys-Dietz syndrome (LDS) is an autosomal dominant arterial aneurysm disease belonging to the spectrum of transforming growth factor β (TGFβ)-associated vasculopathies. In its most typical form it is characterized by the presence of hypertelorism, bifid uvula/cleft palate and aortic aneurysm and/or arterial tortuosity. LDS is caused by heterozygous loss of function mutations in the genes encoding TGFβ receptor 1 and 2 (TGFBR1 and −2), which lead to a paradoxical increase in TGFβ signaling. To address this apparent paradox and to gain more insight into the pathophysiology of aneurysmal disease, we characterized a new Tgfbr1 mouse model carrying a p.Y378* nonsense mutation. Study of the natural history in this model showed that homozygous mutant mice die during embryonic development due to defective vascularization. Heterozygous mutant mice aged 6 and 12 months were morphologically and (immuno)histochemically indistinguishable from wild-type mice. We show that the mutant allele is degraded by nonsense mediated mRNA decay, expected to result in haploinsufficiency of the mutant allele. Since this haploinsufficiency model does not result in cardiovascular malformations, it does not allow further study of the process of aneurysm formation. In addition to providing a comprehensive method for cardiovascular phenotyping in mice, the results of this study confirm that haploinsuffciency is not the underlying genetic mechanism in human LDS.