Relative safety factors against global buckling, anchorage rotation, and tissue rupture in wheat.

The objective of this study was to quantify the effect of specific physical and biological factors on the relative likelihood of biomechanical failure in wheat. Wind-related crop damage is a major obstacle to wheat production that costs several billion dollars per year. The four factors varied in this study were breeding line, dwarfing gene dose, soil type, and fertilization. A theoretical model describing the dynamic structural response of living plants was used to define margins of safety against global buckling, anchorage rotation, and tissue rupture. These relative safety factors were defined for each treatment in comparison with a tall wheat variety selected from a breeding line called Seri and grown in sandy soil with low fertilization. Compared to this reference, the relative safety factor against global buckling was increased (+39%, p<0.01), and the relative safety factor against anchorage rotation was decreased (-11%, p<0.025), by one allele of the dwarfing gene. The relative safety factor against tissue rupture was unaffected by the dwarfing gene but was consistently lower (-26%, p<0.01) in a second breeding line called Kauz. Soil type and fertility did not affect the relative safety factors and this negative finding was significant at p<0.05. The key finding was that the strength of wheat was affected more by genetic rather than by environmental factors, which suggests that some varieties are intrinsically more robust than others. Also, the relative safety factor against anchorage rotation was inversely proportional to the relative safety factor against buckling, which suggests that there are competing constraints on the dynamic structural behavior of wheat.

ROC and LROC analyses of the effects of lesion contrast, size, and signal-to-noise ratio on detectability in PET images.

UNLABELLED: Image quality in PET is typically assessed using measures such as contrast recovery, noise variation, and signal-to-noise ratio (SNR). However, these criteria do not directly reflect performance in the clinical use of the images. Lesion detection is a critical task in the clinical interpretation of many PET studies. A receiver operating characteristic (ROC) study is an accepted method for quantitatively evaluating detection performance with respect to factors that influence image quality. ROC and localization ROC (LROC) analyses were conducted to investigate the effects of lesion contrast, SNR, and size on detectability of hot lesions in PET images. METHODS: A thorax phantom was imaged with spheres of 3 sizes simulating lesions (0.45, 1.0, and 1.9 mL). The relative activity in the lesions and the total number of counts acquired were each varied by factors of 2 to ascertain the effects of contrast and SNR, respectively. Measured attenuation correction and a standard reconstruction protocol were used. Three nuclear medicine physicians and 6 medical physicists participated as readers, rating each image and indicating the suspected lesion location. The area under the calculated ROC and LROC curves (Az and Az,LROC) were used as measures of detection performance. RESULTS: Detection performance was shown to increase from virtually random (Az approximately 0.5, Az,LROC approximately 0.2) to superior (Az > 0.9, Az,LROC > 0.9) as lesion contrast was increased by 50% and as lesion SNR was doubled. Detection performance was not seen to vary when comparison was made using image-based measures alone. CONCLUSION: This study quantitatively shows that moderate increases in the image-based measures of lesion contrast and SNR give a relatively large increase in the task-based measure of lesion detection as measured by ROC and LROC analyses. Thus, techniques that give modest increases in lesion contrast or SNR are expected to improve detection. Results will be useful in evaluating improvement in detection for various reconstruction, acquisition, and data analysis methods that enhance contrast or noise performance.

Performance evaluation of microPET: a high-resolution lutetium oxyorthosilicate PET scanner for animal imaging.

UNLABELLED: A new dedicated PET scanner, microPET, was designed and developed at the University of California, Los Angeles, for imaging small laboratory animals. The goal was to provide a compact system with superior spatial resolution at a fraction of the cost of a clinical PET scanner. METHODS: The system uses fiberoptic readout of individually cut lutetium oxyorthosilicate (LSO) crystals to achieve high spatial resolution. Each microPET detector consists of an 8 x 8 array of 2 x 2 x 10-mm LSO scintillation crystals that are coupled to a 64-channel photomultiplier tube by optical fibers. The tomograph consists of 30 detectors in a continuous ring with a 17.2-cm diameter and fields of view (FOVs) of 11.25 cm in the transaxial direction and 1.8 cm in the axial direction. The system has eight crystal rings and no interplane septa. It operates exclusively in the three-dimensional mode and has an electronically controlled bed that is capable of wobbling with a radius of 300 microm. We describe the performance of the tomograph in terms of its spatial, energy and timing resolution, as well as its sensitivity and counting-rate performance. We also illustrate its overall imaging performance with phantom and animal studies that demonstrate the potential applications of this device to biomedical research. RESULTS: Images reconstructed with three-dimensional filtered backprojection show a spatial resolution of 1.8 mm at the center of the FOV (CFOV), which remains <2.5 mm for the central 5 cm of the transaxial FOV. The resulting volumetric resolution of the system is <8 microL. The absolute system sensitivity measured with a 0.74 MBq (20 microCi) 68Ge point source at the CFOV is 5.62 Hz/kBq. The maximum noise equivalent counting rate obtained with a 6.4-cm diameter cylinder spanning the central 56% of the FOV is 10 kcps, whereas the scatter fraction is 37% at the CFOV for an energy window of 250-650 keV and the same diameter cylinder. CONCLUSION: This is the first PET scanner to use the new scintillator LSO and uses a novel detector design to achieve high volumetric spatial resolution. The combination of imaging characteristics of this prototype system (resolution, sensitivity, counting-rate performance and scatter fraction) opens up new possibilities in the study of animal models with PET.

ROC and localization ROC analyses of lesion detection in whole-body FDG PET: effects of acquisition mode, attenuation correction and reconstruction algorithm.

UNLABELLED: Receiver operating characteristic (ROC) and localization ROC (LROC) studies were performed to compare lesion detection at the borderline of detectability on images reconstructed with two-dimensional filtered backprojection (FBP) without attenuation correction (a common clinical protocol), three-dimensional FBP without attenuation correction, two-dimensional FBP with segmented attenuation correction and a two-dimensional iterative maximum a posteriori (MAP) algorithm using attenuation correction. Lung cancer was the model for the study because of the prominent role of 18F-fluorodeoxyglucose PET in the staging of lung cancer and the importance of lesion detection for staging. METHODS: Simulated lung cancer lesions were added to two-dimensional and three-dimensional PET data from healthy volunteers. Data were reconstructed using the four methods. Four nuclear medicine physicians evaluated the images. Detection performance with each method was compared using ROC and LROC analysis. Jackknife analysis provided estimates of statistical significance for differences across all readers for the ROC results. RESULTS: ROC and LROC results indicated statistically significant degradation in detection performance with three-dimensional acquisition (average area under ROC curves [Az] 0.51; average area under LROC curves [A(z,LROC)] 0.13) and segmented attenuation correction (average Az 0.59; average Az,LROC 0.29) compared with two-dimensional FBP without attenuation correction (average Az 0.79; average A(z,LROC) 0.54). ROC and LROC results indicated an improvement in detection performance with iterative MAP reconstruction (average Az 0.83; average A(z,LROC) 0.64) compared with two-dimensional FBP reconstruction; this improvement was not statistically significant. CONCLUSION: Use of segmented attenuation correction or three-dimensional acquisition with FBP reconstruction is not expected to improve detection of lung lesions on whole-body PET images compared with images with two-dimensional FBP without attenuation correction. The potential improvement in detection obtained with an iterative MAP reconstruction method is small compared with that obtained with two-dimensional FBP without attenuation correction.

High-resolution 3D Bayesian image reconstruction using the microPET small-animal scanner.

A Bayesian method is described for reconstruction of high-resolution 3D images from the microPET small-animal scanner. Resolution recovery is achieved by explicitly modelling the depth dependent geometric sensitivity for each voxel in combination with an accurate detector response model that includes factors due to photon pair non-collinearity and inter-crystal scatter and penetration. To reduce storage and computational costs we use a factored matrix in which the detector response is modelled using a sinogram blurring kernel. Maximum a posteriori (MAP) images are reconstructed using this model in combination with a Poisson likelihood function and a Gibbs prior on the image. Reconstructions obtained from point source data using the accurate system model demonstrate a potential for near-isotropic FWHM resolution of approximately 1.2 mm at the center of the field of view compared with approximately 2 mm when using an analytic 3D reprojection (3DRP) method with a ramp filter. These results also show the ability of the accurate system model to compensate for resolution loss due to crystal penetration producing nearly constant radial FWHM resolution of 1 mm out to a 4 mm radius. Studies with a point source in a uniform cylinder indicate that as the resolution of the image is reduced to control noise propagation the resolution obtained using the accurate system model is superior to that obtained using 3DRP at matched background noise levels. Additional studies using pie phantoms with hot and cold cylinders of diameter 1-2.5 mm and 18FDG animal studies appear to confirm this observation.

An evaluation of exact and approximate 3-D reconstruction algorithms for a high-resolution, small-animal PET scanner.

MicroPET is a low-cost, high-resolution positron emission tomography (PET) scanner designed for imaging small animals. MicroPET operates exclusively without septa, acquiring fully three-dimensional (3-D) data sets. The performance of the projection-reprojection (3DRP), variable axial rebinning (VARB), single slice rebinning (SSRB), and Fourier rebinning (FORE) methods for reconstruction of microPET data were evaluated. The algorithms were compared with respect to resolution, noise variance, and reconstruction time. Results suggested that the 3DRP algorithm gives the best combination of resolution and noise performance in 9 min of reconstruction time on a Sun UltraSparc I workstation. The FORE algorithm provided the most acceptable accelerated method of reconstruction, giving similar resolution performance with a 10%-20% degradation in noise variance in under 2 min. Significant degradation in the axial resolution was measured with the VARB and SSRB methods, offsetting the decrease in reconstruction time achieved with those methods. In-plane angular mashing of the 3-D data before reconstruction led to a 50% reduction in reconstruction time but also introduced unacceptable tangential blurring artifacts. This thorough evaluation of analytical 3-D reconstruction techniques allowed for optimal selection of a reconstruction method for the diverse range of microPET applications.

Origin of cartilage laminae in MRI.

To understand the origin of the laminated appearance of cartilage in MRI (the magic angle effect), microscopic MRI (mu MRI) experiments were performed at 14-microns pixel resolution on normal canine articular cartilage from the shoulder joints. Two-dimensional images of the spin-spin relaxation time (T2) of the cartilage-bone plug at two angles (0 degree and 55 degrees) were calculated quantitatively. A distinct T2 anisotropy was observed as a function of the cartilage tissue depth. The surface and the deep regions exhibit strong orientational dependence of T2, whereas the upper-middle region exhibits little orientational dependence of T2. These three mu MRI regions correspond approximately to the three histologic zones in cartilage tissue. The results from the bulk T2 measurements agreed with these mu MRI results. Our studies show that the laminated appearance of cartilage in MRI is caused by T2 anisotropy of the tissue. We further suggest that the molecular origin of the T2 anisotropy is the nuclear dipolar interaction. The structure of the cartilage tissue indicates that the collagen meshwork defines this T2 anisotropy. The results show that the T2 anisotropy provides an indirect but sensitive indicator for the orientation of macromolecular structures in cartilage. The clinical implications of this anisotropy are discussed.

Variations in composition of cartilage from the shoulder joints of young adult dogs at risk for developing canine hip dysplasia.

OBJECTIVE: To determine whether the composition of cartilage from the shoulder joints of dogs varied with the risk of developing canine hip dysplasia (CHD). DESIGN: Observational study. ANIMALS: 12 skeletally mature (approx 1 year old) Labrador Retrievers. PROCEDURE: Dogs were classified as having a low, moderate, or high risk of developing CHD on the basis of distraction indices. Cartilage was harvested from the craniolateral and weight-bearing regions of the humeral heads, and wet weight per unit area and dry, glycosaminoglycan, and fibronectin contents were determined. RESULTS: Glycosaminoglycan and dry contents did not vary among risk groups. For cartilage from the craniolateral region of the humeral head, wet weight per unit area and fibronectin content increased as risk of developing CHD increased. Wet weight and fibronectin content of cartilage from the weight-bearing region of the humeral head did not vary among risk groups. CLINICAL IMPLICATIONS: Dogs that have a high risk of developing CHD are also more likely to develop osteoarthritis of the shoulder joint. The observed increases in wet weight per unit area and fibronectin content in cartilage from the craniolateral region of the humeral head in dogs at a high risk of developing CHD may be early sings of incipient osteoarthritis.

Swelling and fibronectin accumulation in articular cartilage explants after cyclical impact.

The objective of this study was to determine if repeated impact could damage living cartilage and lead to osteoarthritis-like changes in its biology. Canine cartilage explants were subjected to impacts of as much as 50 MPa once every 5 seconds for 30 minutes. On each impact cycle, the loading rate was 100 MPa/sec to the assigned peak stress, which was held for 1 second. After impact testing, the cartilage was kept in defined culture for as long as 10 days. Radiosulfate incorporation in the region that received direct impact varied with load 0-4 hours after impact, but it did not vary with load at 20-24 hours after impact. Even so, most explants were visibly damaged by 20 or 50 MPa, and there was subtle evidence of damage from impacts of 5 or 10 MPa. For example, ion-induced swelling in 0.01 M NaCl was increased, suggesting that the physical integrity of the matrix was reduced relative to controls. Self-diffusion of water, measured by proton magnetic resonance imaging was also increased in the deeper zones of the explant, consistent with changes in structure at the molecular level. Ten days after impact, the water content and the fibronectin content of the loaded region of the explant were both increased. In combination, these osteoarthritis-like changes suggested that the physical strength of normal cartilage limits its ability to withstand cyclical impact.

Effect of methylprednisolone and mechanical loading on canine articular cartilage in explant culture.

The objective of this study was to assess the effect of mechanical load on articular cartilage after in vitro corticosteroid exposure. Canine humeral cartilage was equilibrated for 4 days in defined medium with a serum substitute, then exposed to methylprednisolone sodium succinate for 20 h at 0, 0.01 or 1.0 mg/ml. After a drug-free recovery period, the explants were subjected to 0, 1 or 10 mega pascals (MPa) for 1 out every 5 s for 20 min, then incubated with [35S]-sulfate and [3H]-leucine for 4 h to measure proteoglycan and protein synthesis, respectively. When the loading occurred 22 h after drug exposure, proteoglycan synthesis was inhibited and protein synthesis, was unaffected by the drug. Both were stimulated by load, relative to controls. When the loading was delayed until 142 h after drug exposure, there was no biosynthetic response to load whether or not the explant had been exposed to the drug. Proteoglycan and protein synthesis 142 h after 0 or 0.01 mg/ml were unchanged or slightly higher than at 22 h, in explants which did not receive load. In contrast, biosynthesis were strongly inhibited 142 h after 1.0 mg/ml, and there was a 40% loss of proteoglycan content, relative to 22 h controls. If explants receiving 1.0 mg/ml also received heavy (10 MPa) loads 142 h later, there was a 17% reduction in total dry content suggesting severe matrix damage. These in vitro results suggest that articular load can help maintain normal cartilage metabolism after corticosteroid exposure, but also suggest that heavy loading after a sub-clinical dose can cause a marked loss of matrix solids.

Self-diffusion monitors degraded cartilage.

This article demonstrates that both the bulk water self-diffusion coefficient (D) and the spatially resolved variation in D for lesion canine cartilage due to osteoarthritis is increased by about 25% over that of surrounding cartilage. This increase in D can be mimicked by enzymatic degradation of cartilage with trypsin, hyaluronidase, and collagenase, or by mechanical means. However, it is established here using excised disks of living cartilage whose proteoglycan and collagen contents were manipulated by biochemical intervention in tissue culture that the diffusion measurement is not sensitive to the proteoglycan content of cartilage. Instead, self-diffusion appears to monitor mesoscopic (nonspecific) tissue damage. These results show that D, measured in a spatially resolved manner by pulsed field gradient nuclear magnetic resonance imaging, can localize regions of cartilage degradation.

Diffusion and relaxation mapping of cartilage-bone plugs and excised disks using microscopic magnetic resonance imaging.

Spatially resolved maps of proton self-diffusion coefficients (D) and relaxation times (T1 and T2) were obtained on cartilage-bone plug samples and on excised disks of canine cartilage at a transverse resolution of 30 microns, using microscopic magnetic resonance imaging (micro-MRI). Results are compared for excised disks of cartilage and intact cartilage-bone plugs. Correlations between the absolute water concentration, the self-diffusion coefficient and the T1 relaxation are reported. The diffusion coefficient is not a linear function of water concentration. The thickness of the disks is 600 microns, compared with the ca. 900 microns observed for the cartilage-bone plugs, presumably due to the absence of the interfacial or tidemark layer of interdigitated cartilage and bone in the former samples. Our results suggest that excised disks of cartilage are excellent models for the articular surface and the first 500 or so microns of tissue. The molecular parameters of spin-spin and spin-lattice relaxation times, as well as the water self-diffusion coefficient, are virtually identical in the two types of samples. However, the cartilage-bone plugs have the additional feature of permitting the study of the tidemark region, a region that likely plays a major role in the transmission of mechanical force.

Effect of compressive loading and unloading on the synthesis of total protein, proteoglycan, and fibronectin by canine cartilage explants.

Full-thickness canine articular cartilage explants were subjected to compressive loads equivalent to a uniaxial stress of 0.025-1.2 MPa. A single cycle (18 h) of unconfined compression resulted in inhibition of total protein, proteoglycan, and fibronectin synthesis. The inhibition of fibronectin synthesis followed that of total protein synthesis. The magnitude of inhibition increased nonlinearly with increasing load levels. The signal that depressed synthesis remained effective for several hours after removal of load, but by 24 h proteoglycan synthesis had partially recovered and fibronectin and protein synthesis had fully recovered and sometimes exceeded the rate of synthesis in free-swelling controls. Forty-eight hours after five cycles of intermittent unconfined compression with similar loads, proteoglycan content and synthesis did not differ in loaded disks and in disks that were never loaded in vitro. Interestingly, the percentage of water in disks that had never been loaded in vitro increased significantly after 10 days in culture, relative to the percentage of water in free-swelling disks on the day of harvest. Intermittent compressive loading in the range of 0.5-1.2 MPa partially prevented this increase. Our results confirmed the previously reported inhibition of biosynthesis with static loading but also suggested that exposure to intermittent compressive loading may help to maintain the normal ratio of dry to wet weight in the explant.

A microstructural model for the anisotropic drained stiffness of articular cartilage.

A constitutive model for articular cartilage is developed to study directional load sharing within the soft biological tissue. Cartilage is idealized as a composite structure whose static mechanical response is dominated by distortion of a sparse fibrous network and by changes in fixed charge density. These histological features of living cartilage are represented in a microstructural analog of the tissue, linking the directionality of mechanical stiffness to the orientation of microstructure. The discretized 'model tissue' is used to define a stiffness tensor relating drained stress and strain over a regime of large deformation. The primary goal of this work was to develop a methodology permitting more complete treatment of anisotropy in the stiffness of cartilage. The results demonstrate that simple oriented microscopic behaviors can combine to produce complicated larger scale response. For the illustrative example of a homogeneous specimen subjected to confined compression, the model predicts a nonlinear anisotropic drained response, with inherent uncertainty at cellular size scales.