Use of microscopic computed-tomography (micro-CT) scanning continues to grow in biomedical research. Laboratory-based micro-CT scanners, laboratory-based nano-CT scanners, and integrated micro-CT ...SPECT and micro-CT PET scanners are now manufactured for "turn-key" operation by a number of commercial vendors. In recent years a number of technical developments in X-ray sources and X-ray imaging arrays have broadened the utility of micro-CT. Of particular interest are photon-counting and energy-resolving detector arrays. These are being explored to maximize micro-CT image grayscale dynamic range and to further increase image contrast by utilizing the unique spectral attenuation characteristics of individual chemical elements. X-ray phase-shift images may increase contrast resolution and reduce radiation exposure. Although radiation exposure is becoming a concern with the drive for increased spatial and temporal resolution, especially for longitudinal studies, gated scans and limited scan-data-set reconstruction algorithms show great potential for keeping radiation exposure to a minimum.
The recent rapid increase in interest in tomographic imaging of small animals and of human (and large animal) organ biopsies is driven largely by drug discovery, cancer detection/monitoring, ...phenotype identification and/or characterization, and development of disease detection methods and monitoring efficacies of drugs in disease treatment. In biomedical applications, micro-computed tomography (CT) scanners can function as scaled-down (i.e., mini) clinical CT scanners that provide a three-dimensional (3-D) image of most, if not the entire, torso of a mouse at image resolution (50-100 microm) scaled proportional to that of a human CT image. Micro-CT scanners, on the other hand, image specimens the size of intact rodent organs at spatial resolutions from cellular (20 microm) down to subcellular dimensions (e.g., 1 microm) and fill the resolution-hiatus between microscope imaging, which resolves individual cells in thin sections of tissue, and mini-CT imaging of intact volumes.
In this work, we investigate optimization-based image reconstruction from few-view (i.e. less than ten views) projections of sparse objects such as coronary-artery specimens. Using optimization ...programs as a guide, we formulate constraint programs as reconstruction programs and develop algorithms to reconstruct images through solving the reconstruction programs. Characterization studies are carried out for elucidating the algorithm properties of 'convergence' (relative to designed solutions) and 'utility' (relative to desired solutions) by using simulated few-view data calculated from a discrete FORBILD coronary-artery phantom, and real few-view data acquired from a human coronary-artery specimen. Study results suggest that carefully designed reconstruction programs and algorithms can yield accurate reconstructions of sparse images from few-view projections.
Micro-computed tomography (micro-CT) is an important tool in biomedical research and preclinical applications that can provide visual inspection of and quantitative information about imaged small ...animals and biological samples such as vasculature specimens. Currently, micro-CT imaging uses projection data acquired at a large number (300-1000) of views, which can limit system throughput and potentially degrade image quality due to radiation-induced deformation or damage to the small animal or specimen. In this work, we have investigated low-dose micro-CT and its application to specimen imaging from substantially reduced projection data by using a recently developed algorithm, referred to as the adaptive-steepest-descent-projection-onto-convex-sets (ASD-POCS) algorithm, which reconstructs an image through minimizing the image total-variation and enforcing data constraints. To validate and evaluate the performance of the ASD-POCS algorithm, we carried out quantitative evaluation studies in a number of tasks of practical interest in imaging of specimens of real animal organs. The results show that the ASD-POCS algorithm can yield images with quality comparable to that obtained with existing algorithms, while using one-sixth to one quarter of the 361-view data currently used in typical micro-CT specimen imaging.
Stereolithography using photo-cross-linkable polymeric biomaterials is an effective technique for fabricating highly complex three-dimensional (3D) scaffolds with controlled microstructures for ...tissue engineering applications. In this study, we have optimized the UV curable polymer solution composition and laser parameters for the stereolithography machine. Poly(propylene fumarate) (PPF) was used as the biomaterial, diethyl fumarate (DEF) was used as the solvent, and bisacrylphosphrine oxide (BAPO) was used as the photoinitiator. Three different weight ratios of PPF/DEF and BAPO contents were characterized by measuring the viscosities and thermal properties of the un-cross-linked solutions and the mechanical properties of the formed scaffolds. After optimizing the resin composition by satisfying both the viscosity limitation and the mechanical requirement, laser parameters such as critical exposure (E c) and penetration depth (D p) were determined from the working curve and the relationship between laser speed and energy by measuring the thickness of predesigned windows fabricated in stereolithography with different ranges of E c and D p. Three-dimensional scaffolds with various pore sizes, pore shapes, and porosities were designed in computer-aided design (CAD) software and were fabricated in stereolithography. The fabricated scaffolds were characterized by measuring external dimensions, porosities, mean pore sizes, and compressive moduli and were compared to the CAD models. Feature accuracy in the xy-plane was achieved and overcuring of the resin in z-axis was minimized. The stereolithographically fabricated scaffolds with controlled microstructures can be useful in diverse tissue engineering applications.
The site of outflow resistance leading to elevated intraocular pressure in primary open-angle glaucoma is believed to be located in the region of Schlemm’s canal inner wall endothelium, its basement ...membrane and the adjacent juxtacanalicular tissue. Evidence also suggests collector channels and intrascleral vessels may have a role in intraocular pressure in both normal and glaucoma eyes. Traditional imaging modalities limit the ability to view both proximal and distal portions of the trabecular outflow pathway as a single unit. In this study, we examined the effectiveness of three-dimensional micro-computed tomography (3D micro-CT) as a potential method to view the trabecular outflow pathway. Two normal human eyes were used: one immersion fixed in 4% paraformaldehyde and one with anterior chamber perfusion at 10 mmHg followed by perfusion fixation in 4% paraformaldehyde/2% glutaraldehyde. Both eyes were postfixed in 1% osmium tetroxide and scanned with 3D micro-CT at 2 μm or 5 μm voxel resolution. In the immersion fixed eye, 24 collector channels were identified with an average orifice size of 27.5 ± 5 μm. In comparison, the perfusion fixed eye had 29 collector channels with a mean orifice size of 40.5 ± 13 μm. Collector channels were not evenly dispersed around the circumference of the eye. There was no significant difference in the length of Schlemm’s canal in the immersed versus the perfused eye (33.2 versus 35.1 mm). Structures, locations and size measurements identified by 3D micro-CT were confirmed by correlative light microscopy. These findings confirm 3D micro-CT can be used effectively for the non-invasive examination of the trabecular meshwork, Schlemm’s canal, collector channels and intrascleral vasculature that comprise the distal outflow pathway. This imaging modality will be useful for non-invasive study of the role of the trabecular outflow pathway as a whole unit.
► 3D micro-CT is an effective, non-invasive imaging method to study the trabecular outflow pathway. ► 3D micro-CT enables outflow pathways to be studied in the context of the whole eye. ► 3D micro-CT enables identification of collector channel number, size, and location around the eye. ► 3D micro-CT will enable study of regional differences in normal and diseased eyes.
Small-animal CT: Its difference from, and impact on, clinical CT Ritman, Erik L.
Nuclear instruments & methods in physics research. Section A, Accelerators, spectrometers, detectors and associated equipment,
10/2007, Letnik:
580, Številka:
2
Journal Article
Recenzirano
Odprti dostop
For whole-body computed tomography (CT) images of small rodents, a voxel resolution of at least 10
−3
mm
3 is needed for scale-equivalence to that currently achieved in clinical CT scanners (∼1
mm
3) ...in adult humans. These “mini-CT” images generally require minutes rather than seconds to complete a scan. The radiation exposure resulting from these mini-CT scans, while higher than clinical CT scans, is below the level resulting in acute tissue damage. Hence, these scans are useful for performing clinical-type diagnostic and monitoring scans for animal models of disease and their response to treatment. “Micro-CT”, with voxel size <10
−5
mm
3, has been useful for imaging isolated, intact organs at an almost cellular level of resolution. Micro-CT has the great advantage over traditional microscopic methods in that it generates detailed three-dimensional images in relatively large, opaque volumes such as an intact rodent heart or kidney. The radiation exposure needed in these scans results in acute tissue damage if used in living animals.
Experience with micro-CT is contributing to exploration of new applications for clinical CT imaging by providing insights into different modes of X-ray image formation as follows:
(1)
Spatial resolution should be sufficient to detect an individual Basic Functional Unit (BFU, the smallest collection of diverse cells, such as hepatic lobule, that behaves like the organ), which requires voxels ∼10
−3
mm
3 in volume, so that the BFUs can be counted.
(2)
Contrast resolution sufficient to allow quantitation of:
(a)
New microvascular growth, which manifests as increased tissue contrast due to X-ray contrast agent in those vessels’ lumens during passage of injected contrast agent in blood.
(b)
Impaired endothelial integrity which manifests as increased opacification and delayed washout of contrast from tissues.
(c)
Discrimination of pathological accumulations of metals such as Fe and Ca, which occur in the arterial wall following hemorrhage or tissue damage.
(3)
Micro-CT can also be used as a test bed for exploring the utility of several modes of X-ray image formation, such as the use of dual-energy X-ray subtraction, X-ray scatter, phase delay and refraction-based imaging for increasing the contrast amongst soft tissue components. With the recent commercial availability of high speed, multi-slice CT scanners which can be operated in dual-energy mode, some of these micro-CT scanner capabilities and insights are becoming implementable in those CT scanners. As a result, the potential diagnostic spectrum that can be addressed with those scanners is broadened considerably.
OBJECTIVE—We hypothesized that apolipoprotein E (apoE)/low-density lipoprotein (LDL) double knockout mice might develop vasa vasorum (VV) in association with advanced lesion formation.
METHODS AND ...RESULTS—Aortas from apoE/LDL mice aged 16, 18, 20, or 80 weeks were infused in situ with Microfil, harvested, and scanned with micro-computed tomography (CT). We characterized plaque volume and CT “density” as well as VV luminal volume along the aorta using Analyze 6.0 software. Results were complemented by a detailed histological plaque classification according to American Heart Association guidelines. From 16 to 80 weeks, plaque volume and VV opacified lumen volume increased with age (P<0.001). The 3-dimensional micro-CT images of arterial and venous VV trees allowed perfusion territories to be delineated. The spatial location and magnitude of VV density and adventitial inflammation were strongly correlated in advanced atherosclerotic lesions (r=0.91) and identified as an independent correlate to advanced lesions. At age 80 weeks, VV luminal volume was increased 20-fold compared with animals at age 16 weeks (P<0.001). Micro-CT showed that adventitial VV communicate with intraplaque microvessels.
CONCLUSION—Our results show that apoE/LDL double knockout mice develop VV and advanced atheromas along the aorta. Lesion volume was closely associated with amount of neovascularization in advanced atheromas.
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