High tibial osteotomy to neutral alignment improves medial knee articular cartilage composition.

PURPOSE: The purpose of this study was to: (1) test the hypothesis that HTO improves articular cartilage composition in the medial compartment without adversely affecting the lateral compartment and patella, and; (2) explore associations between knee alignment and cartilage composition after surgery. METHODS: 3T MRI and standing radiographs were obtained from 34 patients before and 1-year after HTO. Articular cartilage was segmented from T2 maps. Mechanical axis angle (MAA), posterior tibial slope, and patellar height were measured from radiographs. Changes in T2 and radiographic measures were assessed using paired t tests, and associations were assessed using Pearson correlation coefficients. RESULTS: The mean (SD) MAA before and after HTO was - 6.5° (2.4) and 0.6° (3.0), respectively. There was statistically significant shortening [mean (95%CI)] of T2 in the medial femur [- 2.8 ms (- 4.2; - 1.3), p < 0.001] and medial tibia [- 2.2 ms (- 3.3; - 1.0), p < 0.001], without changes in the lateral femur [- 0.5 ms (- 1.6; 0.6), p = 0.3], lateral tibia [0.2 ms (- 0.8; 1.1), p = NS], or patella [0.5 ms (- 1.0; 2.1), p = NS). Associations between radiographic measures and T2 were low. 23% of the increase in lateral femur T2 was explained by postoperative posterior tibial slope (r = 0.48). CONCLUSION: Performing medial opening wedge HTO without overcorrection improves articular cartilage composition in the medial compartment of the knee without compromising the lateral compartment or the patella. Although further research is required, these results suggest HTO is a disease structure-modifying treatment for knee OA.

Extending the dynamic range of biomedical micro-computed tomography for application to geomaterials.

BACKGROUND: X-ray computed tomography (CT) can non-destructively examine objects by producing three-dimensional images of their internal structure. Although the availability of biomedical micro-CT offers the increased access to scanners, CT images of dense objects are susceptible to artifacts particularly due to beam hardening. OBJECTIVE: This study proposes and evaluates a simple semi-empirical correction method for beam hardening and scatter that can be applied to biomedical scanners. METHODS: Novel calibration phantoms of varying diameters were designed and built from aluminum and poly[methyl-methacrylate]. They were imaged using two biomedical micro-CT scanners. Absorbance measurements made through different phantom sections were fit to polynomial and inversely exponential functions and used to determine linearization parameters. Corrections based on the linearization equations were applied to the projection data before reconstruction. RESULTS: Correction for beam hardening was achieved when applying both scanners with the correction methods to all test objects. Among them, applying polynomial correction method based on the aluminum phantom provided the best improvement. Correction of sample data demonstrated a high agreement of percent-volume composition of dense metallic inclusions between using the Bassikounou meteorite from the micro-CT images (13.7%) and previously published results using the petrographic thin sections (14.6% 8% metal and 6.6% troilite). CONCLUSIONS: Semi-empirical linearization of X-ray projection data with custom calibration phantoms allows accurate measurements to be obtained on the radiodense samples after applying the proposed correction method on biomedical micro-CT images.

C57BL/6 mice are resistant to joint degeneration induced by whole-body vibration.

OBJECTIVE: Whole-body vibration (WBV) platforms are commercially available devices that are used clinically to treat numerous musculoskeletal conditions based on their reported ability to increase bone mineral density and muscle strength. Despite widespread use, there is an alarming lack of understanding of the direct effects of WBV on joint health. Previous work by our lab demonstrated that repeated exposure to WBV using protocols that model those used clinically, induces intervertebral disc (IVD) degeneration and osteoarthritis-like damage in the knee of skeletally mature, male mice of a single outbred strain (CD-1). The present study examined whether exposure to WBV induces similar deleterious effects in a genetically different strain of mouse (C57BL/6). DESIGN: Male 10-week-old C57BL/6 mice were exposed to vertical sinusoidal WBV for 30 min/day, 5 days/week, for 4 or 8 weeks using previously reported protocols (45 Hz, 0.3 g peak acceleration). Following WBV, joint tissues were examined using histological analysis and gene expression was quantified using real-time PCR (qPCR). RESULTS: Our analyses show a lack of WBV-induced degeneration in either the knee or IVDs of C57BL/6 mice exposed to WBV for 4 or 8 weeks, in direct contrast to the WBV-induced damage previously reported by our lab in CD-1 mice. CONCLUSIONS: Together with previous studies from our group, the present study demonstrates that the effects of WBV on joint tissues vary in a strain-specific manner. These findings highlight the need to examine genetic or physiological differences that may underlie susceptibility to the deleterious effects of WBV on joint tissues.

Whole-body vibration of mice induces articular cartilage degeneration with minimal changes in subchondral bone.

OBJECTIVE: Low-amplitude, high-frequency whole-body vibration (WBV) has been adopted for the treatment of musculoskeletal diseases including osteoarthritis (OA); however, there is limited knowledge of the direct effects of vibration on joint tissues. Our recent studies revealed striking damage to the knee joint following exposure of mice to WBV. The current study examined the effects of WBV on specific compartments of the murine tibiofemoral joint over 8 weeks, including microarchitecture of the tibia, to understand the mechanisms associated with WBV-induced joint damage. DESIGN: Ten-week-old male CD-1 mice were exposed to WBV (45 Hz, 0.3 g peak acceleration; 30 min/day, 5 days/week) for 4 weeks, 8 weeks, or 4 weeks WBV followed by 4 weeks recovery. The knee joint was evaluated histologically for tissue damage. Architecture of the subchondral bone plate, subchondral trabecular bone, primary and secondary spongiosa of the tibia was assessed using micro-CT. RESULTS: Meniscal tears and focal articular cartilage damage were induced by WBV; the extent of damage increased between 4 and 8-week exposures to WBV. WBV did not alter the subchondral bone plate, or trabecular bone of the tibial spongiosa; however, a transient increase was detected in the subchondral trabecular bone volume and density. CONCLUSIONS: The lack of WBV-induced changes in the underlying subchondral bone suggests that damage to the articular cartilage may be secondary to the meniscal injury we detected. Our findings underscore the need for further studies to assess the safety of WBV in the human population to avoid long-term joint damage.

Iodine potassium iodide improves the contrast-to-noise ratio of micro-computed tomography images of the human middle ear.

High-resolution imaging of middle-ear geometry is necessary for finite-element modeling. Although micro-computed tomography (microCT) is widely used because of its ability to image bony structures of the middle ear, it is difficult to visualize soft tissues - including the tympanic membrane and the suspensory ligaments/tendons - because of lack of contrast. The objective of this research is to quantitatively evaluate the efficacy of iodine potassium iodide (IKI) solution as a contrast agent. Six human temporal bones were used in this experiment, which were obtained in right-left pairs, from three cadaveric heads. All bones were fixed using formaldehyde. Three bones (one from each pair) were stained in IKI solution for 2 days, whereas the other three were not stained. Samples were scanned using a microCT system at a resolution of 20 µm. Eight soft tissues in the middle ear were segmented: anterior mallear ligament, incudomallear joint, lateral mallear ligament, posterior incudal ligament, stapedial annular ligament, stapedius muscle, tympanic membrane and tensor tympani muscle. Contrast-to-noise ratios (CNRs) of each soft tissue were calculated for each temporal bone. Combined CNRs of the soft tissues in unstained samples were 6.1 ± 3.0, whereas they were 8.1 ± 2.7 in stained samples. Results from Welch's t-test indicate significant difference between the two groups at a 95% confidence interval. Results for paired t-tests for each of the individual soft tissues also indicated significant improvement of contrast in all tissues after staining. Relatively large soft tissues in the middle ear such as the tympanic membrane and the tensor tympani muscle were impacted by staining more than smaller tissues such as the stapedial annular ligament. The increase in contrast with IKI solution confirms its potential application in automatic segmentation of the middle-ear soft tissues.

Quantifying lung morphology with respiratory-gated micro-CT in a murine model of emphysema.

Non-invasive micro-CT imaging techniques have been developed to investigate lung structure in free-breathing rodents. In this study, we investigate the utility of retrospectively respiratory-gated micro-CT imaging in an emphysema model to determine if anatomical changes could be observed in the image-derived quantitative analysis at two respiratory phases. The emphysema model chosen was a well-characterized, genetically altered model (TIMP-3 knockout mice) that exhibits a homogeneous phenotype. Micro-CT scans of the free-breathing, anaesthetized mice were obtained in 50 s and retrospectively respiratory sorted and reconstructed, providing 3D images representing peak inspiration and end expiration with 0.15 mm isotropic voxel spacing. Anatomical measurements included the volume and CT density of the lungs and the volume of the major airways, along with the diameters of the trachea, left bronchus and right bronchus. From these measurements, functional parameters such as functional residual capacity and tidal volume were calculated. Significant differences between the wild-type and TIMP-3 knockout groups were observed for measurements of CT density over the entire lung, indicating increased air content in the lungs of TIMP-3 knockout mice. These results demonstrate retrospective respiratory-gated micro-CT, providing images at multiple respiratory phases that can be analyzed quantitatively to investigate anatomical changes in murine models of emphysema.

Development of a customized density-modulus relationship for use in subject-specific finite element models of the ulna.

Assigning an appropriate density-modulus relationship is an important factor when applying inhomogeneous material properties to finite element models of bone. The purpose of this study was to develop a customized density-modulus equation for the distal ulna, using beam theory combined with experimental results. Five custom equations of the form E= ap(b) were used to apply material properties to models of eight ulnae. All equations passed through a point (1.85, Ec), where p = 1.85 g/cm3 represents the average density of cortical bone. For custom equations (1) to (3), Ec was predicted using beam theory, and the value of b was varied within the range reported in the literature. Custom equations (4) and (5) used other values of Ec from the literature, while keeping b constant. Results obtained from the custom equations were compared with those from other equations in the literature, and with experimental results. The beam theory analysis predicted Ec = 21 +/- 1.6 GPa, and the three custom equations using this value tended to have the lowest errors. The power of the equations did not affect the results as much as the value used for Ec. Overall, a customized density-modulus relationship for the ulna was generated, which provided improved results over using previously reported density-modulus equations.

Implementation of dual- and triple-energy cone-beam micro-CT for postreconstruction material decomposition.

Micro-CT has become a powerful tool for small animal research, having the ability to obtain high-resolution in vivo and ex vivo images for analyzing bone mineral content, organ vasculature, and bone microarchitecture extraction. The use of exogenous contrast agents further extends the use of micro-CT techniques, but despite advancements in contrast agents, single-energy micro-CT is still limited in cases where two different materials share similar grey-scale intensity values. This study specifically addresses the development of multiple-energy cone-beam micro-CT, for applications where bone must be separated from blood vessels filled with a Pb-based contrast material (Microfil) in ex vivo studies of rodents and tissue specimens. The authors report the implementation of dual- and triple-energy CT algorithms for material-specific imaging using postreconstruction decomposition of micro-CT data; the algorithms were implemented on a volumetric cone-beam micro-CT scanner (GE Locus Ultra). For the dual-energy approach, extrinsic filtration was applied to the x-ray beam to produce spectra with different proportions of x rays above the K edge of Pb. The optimum x-ray tube energies (140 kVp filtered with 1.45 mm Cu and 96 kVp filtered with 0.3 mm Pb) that maximize the contrast between bone and Microfil were determined through numerical simulation. For the triple-energy decomposition, an additional low-energy spectrum (70 kVp, no added filtration) was used. The accuracy of decomposition was evaluated through simulations and experimental verification of a phantom containing a cortical bone simulating material (SB3), Microfil, and acrylic. Using simulations and phantom experiments, an accuracy greater than 95% was achieved in decompositions of bone and Microfil (for noise levels lower than 11 HU), while soft tissue was separated with accuracy better than 99%. The triple-energy technique demonstrated a slightly higher, but not significantly different, decomposition accuracy than the dual-energy technique for the same achieved noise level in the micro-CT images acquired at the multiple energies. The dual-energy technique was applied to the decomposition of an ex vivo rat specimen perfused with Microfil; successful decomposition of the bone and Microfil was achieved, enabling the visualization and characterization of the vasculature both in areas where the vessels traverse soft tissue and when they are surrounded by bone. In comparison, in single energy micro-CT, vessels surrounded by bone could not be distinguished from the cortical bone, based on grey-scale intensity alone. This work represents the first postreconstruction application of material-specific decomposition that directly takes advantage of the K edge characteristics of a contrast material injected into an animal specimen; the application of the technique resulted in automatic, accurate segmentation of 3D micro-CT images into bone, vessel, and tissue components. The algorithm uses only reconstructed images, rather than projection data, and is calibrated by an operator with signal values in regions identified as being comprised entirely of either cortical bone, contrast-enhanced vessel, or soft tissue; these required calibration values are observed directly within reconstructed CT images acquired at the multiple energies. These features facilitate future implementation on existing research micro-CT systems.

In vivo small-animal imaging using micro-CT and digital subtraction angiography.

Small-animal imaging has a critical role in phenotyping, drug discovery and in providing a basic understanding of mechanisms of disease. Translating imaging methods from humans to small animals is not an easy task. The purpose of this work is to review in vivo x-ray based small-animal imaging, with a focus on in vivo micro-computed tomography (micro-CT) and digital subtraction angiography (DSA). We present the principles, technologies, image quality parameters and types of applications. We show that both methods can be used not only to provide morphological, but also functional information, such as cardiac function estimation or perfusion. Compared to other modalities, x-ray based imaging is usually regarded as being able to provide higher throughput at lower cost and adequate resolution. The limitations are usually associated with the relatively poor contrast mechanisms and potential radiation damage due to ionizing radiation, although the use of contrast agents and careful design of studies can address these limitations. We hope that the information will effectively address how x-ray based imaging can be exploited for successful in vivo preclinical imaging.

In vivo characterization of lung morphology and function in anesthetized free-breathing mice using micro-computed tomography.

Lung morphology and function in human subjects can be monitored with computed tomography (CT). Because many human respiratory diseases are routinely modeled in rodents, a means of monitoring the changes in the structure and function of the rodent lung is desired. High-resolution images of the rodent lung can be attained with specialized micro-CT equipment, which provides a means of monitoring rodent models of lung disease noninvasively with a clinically relevant method. Previous studies have shown respiratory-gated images of intubated and respirated mice. Although the image quality and resolution are sufficient in these studies to make quantitative measurements, these measurements of lung structure will depend on the settings of the ventilator and not on the respiratory mechanics of the individual animals. In addition, intubation and ventilation can have unnatural effects on the respiratory dynamics of the animal, because the airway pressure, tidal volume, and respiratory rate are selected by the operator. In these experiments, important information about the symptoms of the respiratory disease being studied may be missed because the respiration is forced to conform to the ventilator settings. In this study, we implement a method of respiratory-gated micro-CT for use with anesthetized free-breathing rodents. From the micro-CT images, quantitative analysis of the structure of the lungs of healthy unconscious mice was performed to obtain airway diameters, lung and airway volumes, and CT densities at end expiration and during inspiration. Because the animals were free breathing, we were able to calculate tidal volume (0.09 +/- 0.03 ml) and functional residual capacity (0.16 +/- 0.03 ml).

Receptor for hyaluronan mediated motility (RHAMM/HMMR) is a novel target for promoting subcutaneous adipogenesis.

Hyaluronan, CD44 and the Receptor for Hyaluronan-Mediated Motility (RHAMM, gene name HMMR) regulate stem cell differentiation including mesenchymal progenitor differentiation. Here, we show that CD44 expression is required for subcutaneous adipogenesis, whereas RHAMM expression suppresses this process. We designed RHAMM function blocking peptides to promote subcutaneous adipogenesis as a clinical and tissue engineering tool. Adipogenic RHAMM peptides were identified by screening for their ability to promote adipogenesis in culture assays using rat bone marrow mesenchymal stem cells, mouse pre-adipocyte cell lines and primary human subcutaneous pre-adipocytes. Oil red O uptake into fat droplets and adiponectin production were used as biomarkers of adipogenesis. Positive peptides were formulated in either collagen I or hyaluronan (Orthovisc) gels then assessed for their adipogenic potential in vivo following injection into dorsal rat skin and mammary fat pads. Fat content was quantified and characterized using micro CT imaging, morphometry, histology, RT-PCR and ELISA analyses of adipogenic gene expression. Injection of screened peptides increased dorsal back subcutaneous fat pad area (208.3 ± 10.4 mm2versus control 84.11 ± 4.2 mm2; p < 0.05) and mammary fat pad size (45 ± 11 mg above control background, p = 0.002) in female rats. This effect lasted >5 weeks as detected by micro CT imaging and perilipin 1 mRNA expression. RHAMM expression suppresses while blocking peptides promote expression of PPARγ, C/EBP and their target genes. Blocking RHAMM function by peptide injection or topical application is a novel and minimally invasive method for potentially promoting subcutaneous adipogenesis in lipodystrophic diseases and a complementary tool to subcutaneous fat augmentation techniques.

Mechanical Forces Exacerbate Periodontal Defects in Bsp-null Mice.

Bone sialoprotein (BSP) is an acidic phosphoprotein with collagen-binding, cell attachment, and hydroxyapatite-nucleating properties. BSP expression in mineralized tissues is upregulated at onset of mineralization. Bsp-null (Bsp(-/-)) mice exhibit reductions in bone mineral density, bone turnover, osteoclast activation, and impaired bone healing. Furthermore, Bsp(-/-) mice have marked periodontal tissue breakdown, with a lack of acellular cementum leading to periodontal ligament detachment, extensive alveolar bone and tooth root resorption, and incisor malocclusion. We hypothesized that altered mechanical stress from mastication contributes to periodontal destruction observed in Bsp(-/-) mice. This hypothesis was tested by comparing Bsp(-/-) and wild-type mice fed with standard hard pellet diet or soft powder diet. Dentoalveolar tissues were analyzed using histology and micro-computed tomography. By 8 wk of age, Bsp(-/-) mice exhibited molar and incisor malocclusion regardless of diet. Bsp(-/-) mice with hard pellet diet exhibited high incidence (30%) of severe incisor malocclusion, 10% lower body weight, 3% reduced femur length, and 30% elevated serum alkaline phosphatase activity compared to wild type. Soft powder diet reduced severe incisor malocclusion incidence to 3% in Bsp(-/-) mice, supporting the hypothesis that occlusal loading contributed to the malocclusion phenotype. Furthermore, Bsp(-/-) mice in the soft powder diet group featured normal body weight, long bone length, and serum alkaline phosphatase activity, suggesting that tooth dysfunction and malnutrition contribute to growth and skeletal defects reported in Bsp(-/-) mice. Bsp(-/-) incisors also erupt at a slower rate, which likely leads to the observed thickened dentin and enhanced mineralization of dentin and enamel toward the apical end. We propose that the decrease in eruption rate is due to a lack of acellular cementum and associated defective periodontal attachment. These data demonstrate the importance of BSP in maintaining proper periodontal function and alveolar bone remodeling and point to dental dysfunction as causative factor of skeletal defects observed in Bsp(-/-) mice.

Rapid small-animal dual-energy X-ray absorptiometry using digital radiography.

Although dual-energy X-ray absorptiometry (DEXA) is an established technique for clinical assessment of areal bone mineral density (BMD), the spatial resolution, signal-to-noise ratio, scan time, and availability of clinical DEXA systems may be limiting factors for small-animal investigations using a large number of specimens. To avoid these limitations, we have implemented a clinical digital radiography system to perform rapid area DEXA analysis on in vitro rat bone specimens. A crossed step-wedge (comprised of epoxy-based materials that mimic the radiographic properties of tissue and bone) was used to calibrate the system. Digital radiographs of bone specimens (pelvis, spine, femur, and tibia from sham-ovariectomized [SHAM] and ovariectomized [OVX] rats) were obtained at 40 kilovolt peak (kVp) and 125 kVp, and the resulting areal BMD values were compared with those obtained with a clinical fan-beam DEXA system (Hologics QDR 4500). Our investigation indicates that the cross-wedge calibrated (CWC) DEXA technique provides high-precision measurements of bone mineral content (BMC; CV = 0.6%) and BMD (CV = 0.8%) within a short acquisition time (<30 s). Areal BMD measurements reported by the CWC-DEXA system are within 8.5% of those reported by a clinical fan-beam scanner, and BMC values are within 5% of the known value of test specimens. In an in vivo application, the CWC-DEXA system is capable of reporting significant differences between study groups (SHAM and OVX) that are not reported by a clinical fan-beam DEXA system, because of the reduced variance and improved object segmentation provided by the CWC-DEXA system.

Use of a C-arm system to generate true three-dimensional computed rotational angiograms: preliminary in vitro and in vivo results.

PURPOSE: To evaluate the potential use of a C-arm mounted X-ray image intensifier (XRII) system to generate three-dimensional computed rotational angiograms during interventional neuroradiologic procedures. METHODS: A clinical angiographic system was modified to allow collection of sufficient views during selective intraarterial contrast injections for CT reconstruction of a 15 x 15 x 15-cm3 volume. Image intensifier distortion and C-arm instabilities were corrected by using image-based techniques. The impact of the pulsatile nature of the vessels during image data acquisition and of the presence of bone on the 3-D reconstructions was investigated by generating 3-D reconstructions of an anesthetized 20-kg pig and of a human skull phantom. RESULTS: A sequence of images sufficient for 3-D reconstruction was acquired in less than 5 seconds. Image intensifier distortion and C-arm instabilities were corrected to subpixel accuracy (0.035 mm and 0.07 mm, respectively). Both the intracranial vessels of the pig and the small, high-contrast structures in the skull were reconstructed with negligible artifacts. CONCLUSIONS: Using a C-arm mounted XRII system, computed rotational angiography can provide true 3-D images of diagnostic quality.

An analysis of the geometry of saccular intracranial aneurysms.

BACKGROUND AND PURPOSE: Our goal was to characterize the geometry of simple-lobed cerebral aneurysms and to find the absolute size of these lesions from angiographic tracings. METHODS: Measurements of angiographic neck width (N), dome height (H), dome diameter (D), and semi-axis height (S) were obtained from tracings of 87 simple-lobed lesions located at the basilar bifurcation (BB), middle cerebral (MCA), anterior communicating (AcomA), posterior communicating (PcomA), superior cerebellar (SCA), and posterior cerebral (PCA) arteries. The following ratios were analyzed as subgroups according to location and as a collective sample: dome diameter/dome height (D/H), dome height/neck width (H/N), dome diameter/neck width (D/N), and dome height/semi-axis height (H/S). Using the parent artery as a reference, aneurysm dimensions were normalized to absolute in vivo size. Estimations were validated using angiographic markers. RESULTS: For the entire sample, mean ratios were D/H = 1.11, D/N = 1.91, and H/N = 1.86. For the H/S ratio, the value was 1.98 for BB, MCA, and PcomA lesions and significantly smaller for the AcomA subgroup, at 1.52. The average sizes (in mm) for these dimensions were N = 3.4 for MCA, 3.0 for AcomA, 3.1 for PcomA, and 6.5 for BB; D = 6.1 for MCA, 5.9 for AcomA, 5.3 for PcomA, and 11.7 for BB; H = 5.6 for MCA, 5.0 for AcomA, 5.3 for PcomA, and 11.3 for BB. On average, BB aneurysms were twice as large as aneurysms at other locations. Good correlations were found between the scaled values for D and N, H and N, and H and D. CONCLUSION: These results have been used to characterize the typical simple-lobed aneurysm geometry and to provide a framework for the development of a method of assessment of treatment choice and outcome on the basis of lesion geometry.

Three-dimensional computed tomographic reconstruction using a C-arm mounted XRII: image-based correction of gantry motion nonidealities.

The image quality of 3D reconstructions produced using a C-arm mounted XRII depends on precise determination of the geometric parameters that describe the detector system in the laboratory frame of reference. We have designed a simplified calibration system that depends on images of a metal sphere, acquired during rotation of the gantry through 200 degrees. Angle-dependent shift corrections are obtained, accounting for nonideal motion in two directions: perpendicular to the axis of rotation and tangential to the circular trajectory (tau), and parallel to the axis of rotation (xi). Projection images are corrected prior to reconstruction using a simple shift-interpolation algorithm. We show that the motion of the gantry is highly reproducible during acquisitions within one day (mean standard deviation in tau and xi is 0.11 mm and 0.08 mm, respectively), and over 21 months (mean standard deviation in tau and xi is 0.10 mm and 0.06 mm, respectively). Reconstruction of a small-bead phantom demonstrates uniformity of the correction algorithm over the full volume of the reconstruction [standard deviation of full-width-half-maximum of the beads is approximately 0.25 pixels (0.13 mm) over the volume of reconstruction]. Our approach provides a simple correction technique that can be applied when trajectory deviations are significant relative to the pixel size of the detector but small relative to the detector field of view, and when the fan angle of the acquisition geometry is small (<20 degrees). A comparison with other calibration techniques in the literature is provided.

A time-delay integration charge-coupled device camera for slot-scanned digital radiography.

We have developed a low-noise digital camera based on a 512 x 96 element CCD operating in the time-delay integration mode. This camera has been combined with an x-ray image intensifier to record radiographic images produced by a scanning slot beam of radiation. This results in the rejection of a large fraction of scattered radiation, without a significant increase in x-ray tube heat loading or image acquisition time. Here we describe the design of our CCD camera and the results of our investigations of camera resolution, linearity, noise, and quantum efficiency. We have found that both the resolution limit (50 mm-1) and the dynamic range (2100) of this novel camera are greater than reported values for conventional video cameras. Applications of this system in digital angiography and mammography are discussed.

Dual-energy x-ray imaging technique for in vitro tissue composition measurement.

A dual-energy in vitro radiographic technique has been developed to study the thickness of tissue and bone within atherosclerotic plaques. Results concerning the accuracy and precision of the thickness measurements using this technique are presented and discussed. Planar radiographs of phantoms were obtained with a low-energy spectrum (45 kVp, no added filtration) and a high-energy spectrum (100 kVp, 2.88-mm copper-added filtration), and then decomposed into bone-equivalent and Lucite basis-material images. Thickness measurements from these images yielded average accuracies of +/- 750 microns for the Lucite images, and +/- 25 microns for the bone-equivalent images. The imprecision (one standard deviation) of the thickness measurements was +/- 192 and +/- 47 microns for the Lucite and the bone-equivalent images, respectively (for thin sections). Although the accuracy and precision of Lucite thickness measurements were not as good as those obtained with other techniques, such as the iodine displacement technique, the accuracy and precision of the bone thickness measurements are shown to be much better. The high accuracy and precision of the bone measurement makes dual energy a very appealing technique for analyzing the physical properties of calcified atherosclerotic plaques in excised arterial specimens.

X-ray imaging technique for in vitro tissue composition measurements using saline/iodine displacement: technique optimization.

An in vitro radiographic technique which uses saline/iodine displacement has been developed to study the thickness of bone-equivalent and soft-tissue-equivalent materials within atherosclerotic plaques in arterial specimens which have been cut open longitudinally and laid flat. Results concerning the optimization of the imaging parameters are presented and discussed. The technique consists of imaging arterial specimens under two different conditions: (1) when it is immersed in an isotonic saline solution, to estimate the calcium content, and (2) when it is immersed in a concentrated iodine solution, to estimate the total thickness of the specimen. Calibration step wedges made out of bone-mimicking and soft-tissue-mimicking materials are imaged simultaneously to generate calibration curves which are used to convert the radiographs into bone-equivalent and soft-tissue-equivalent thickness images. The optimal spectral parameters were determined to be 45 and 100 kVp for the saline and the iodine images, respectively, with a significant amount of added filtration for both images. Inherent systematic inaccuracies due to (1) the nonidealities due to linear attenuation coefficient mismatch between tissue and calibration materials and (2) beam hardening due to heel effect are determined theoretically, and can be used to correct a set of bone-equivalent and the soft-tissue-equivalent images to within +/- 6 microns with an ideal, noise-free imaging system.

Three-dimensional computed tomographic reconstruction using a C-arm mounted XRII: correction of image intensifier distortion.

X-ray image intensifiers (XRIIs) have many applications in diagnostic imaging including acquisition of near-real-time projection images of the intracranial and coronary vasculature. Recently, there has been some interest in using this projection data to generate three-dimensional (3-D) computed tomographic (CT) reconstructions. The XRII and x-ray tube are rotated around the object, acquiring sufficient data for the simultaneous reconstruction of many transverse slices. Three-dimensional reconstructions are compromised, however, if the projection data is geometrically distorted in any way. Previous studies have shown the distortion in XRIIs to be substantial and to be highly angular dependent. In this paper, we present a global correction technique which provides a table of correction coefficients for an image acquired at any arbitrary angle about the patient. The coefficients are generated using a linear least-squares fit between the detected and known locations of a grid of small steel beads which is attached to the XRII (27 cm nominal diameter). We have performed corrections on 100 images obtained during rotation of the gantry through 200 degrees and find that a fifth-order polynomial provides optimum image distortion reduction (mean residual distortion of 0.07 pixels), however, fourth-order polynomials provide sufficient distortion reduction for our application (mean residual displacement of 0.1 pixels). Using sixth-order polynomials does not provide a statistically significant reduction in image distortion. The spatial distribution of residual distortion did not demonstrate any particular pattern over the face of the XRII. Image angle and coefficient angle must be known to within +/- 2 degrees in order to keep the mean residual distortion be approximately 0.5 pixels.