A pilot study has been conducted in which coronary arteries subject to re-stenosis after angioplasty and stenting have been irradiated following further angioplasty. The method of irradiation has been to use radioactive 188Re in an angioplasty balloon. This paper considers all aspects of the procedure including elution of the rhenium from a tungsten/rhenium generator, its concentration, dispensing and safe delivery to the patient using specially designed equipment to reduce staff doses and radioactive spills. In the pilot study of 28 lesions in 26 patients only 1 was recorded as having angiographic re-stenosis in the treated region at 6 months although 4 other patients had edge re-stenosis. This represents less than 18% re-stenosis in a population that would have been expected to exhibit at least 50% re-stenosis at 6 months. A total of 72 patients have been treated either in the pilot study or a subsequent trial. In only one case has a minor spill of radioactivity occurred and in no case has the balloon burst. Radiation doses to staff are approximately 20 microSv per procedure and are therefore not of serious consequence. It is concluded that this procedure is safe, feasible and effective in reducing in-stent re-stenosis.

Radiation dose distributions have been calculated for 188Re and 32P activity on a coronary artery stent. The doses have been calculated both as a function of position along the stent and of depth into the artery wall. Comparisons of the dose from identical activities of 188Re and 32P on the stent show that the major differences arise from the different half-lives of the two activities. Coating the activity onto three surfaces of the stent rather than just the outside surface is found to reduce the dose by approximately 8 to 9%. Similarly, the effect of ignoring the attenuation in the stainless steel of the stent is to increase doses by 11 to 17%. Consideration is also given to the effect of the prolonged treatment times associated with a radioactive stent compared with the more common treatment over several minutes. It is shown that extended treatment may require between two and eight times the single dose to achieve the same effect depending on factors such as the radionuclide used, the dose required and the assumed cell survival curve. On the assumption that an instantaneous dose of 18 Gy at a depth of 1 mm into the artery would be required for successful prevention of neointimal hyperplasia, activities required for a stent coated with 188Re and 32P are tabulated.

The radiation dosimetry associated with the use of the beta particle emitter 188Re in an angioplasty balloon is investigated for the case when the balloon has an elliptical rather than circular cross section and when iodinated x-ray contrast medium is included inside the balloon. It is found that the elliptical cross section introduces significant dose corrections when the eccentricity of the ellipse is equal to or greater than 0.7. However, for cases where the artery is nearly circular in cross section, the corrections are likely to be small. As expected, the dose is reduced along the major axis of the ellipse and increased along the minor axis. The corrections are greatest at larger distances from the surface of the balloon. The effect on dose of contrast in the balloon is significant for 33% Omnipaque in saline. Since this is a typical concentration of contrast that is used for imaging the radiation-filled balloon, correction for the effects of contrast medium in the balloon should in general be applied. To enable corrections to be readily applied for other types and concentrations of contrast media, formulas have been derived that allow the dose correction to be calculated for a range of balloon diameters and at various distances from the surface of the balloon. To undertake this calculation, the elemental composition and density of the material in the balloon needs to be known.

A surgical light source has been examined to determine the potential for retinal damage to staff in the operating theatre. It has been shown that under certain circumstances the light source examined can give an irradiance at the cornea which is well in excess of accepted safety standards. Calculation using data on the retinal irradiance required to produce retinal damage indicates that for an accidental exposure at a distance of 500 mm there is a significant possibility of retinal damage. At closer distances the probability of retinal damage is even higher. It is possible that other surgical light sources produce a similar degree of hazard and hospitals should establish suitable safety measures where necessary.

A CT scanner has been used to measure the electron density of a range of bone types in vivo. It is shown that there is a linear relationship between the CT number of bone and its electron density, which is expected theoretically if different bone types are treated as a variable mixture of osseous material and marrow. A method of calibrating any CT scanner using a simply prepared solution is proposed, which should enable electron densities of bone to be estimated from CT numbers with an accuracy of 5%.

The basic partial differential formulation for small differences has been applied to the equations for the inversion recovery and saturation recovery sequences with spin-echo rephase pulses and the spin-echo sequence itself. The result is a generalized expression which is proportional to tissue discrimination expressed as the signal-difference-to-noise ratio for a pair of tissues. The expression is a function of the fractional differences in the tissue relaxation times and proton densities, T1, T2, and n, respectively, and the sequence parameters TR and TI, or TE. From it can be derived the conditions which lead to optimum tissue discrimination for a given pulse sequence. It is also possible to predict the optimum pulse sequence to use for any pair of tissues of interest. The method requires a knowledge of the fractional differences in T1, T2, and n for both tissues.

A simple and rapid technique to measure the proton beam energy in the external beam line of a medical cyclotron has been examined. A stack of 0.1 mm thick high purity copper (Cu) foils was bombarded and the relative activity of 65Zn produced in each foil was compared to a computational model that predicted activity, based on proton stopping power, reaction cross-sectional data, and beam energy. In the model, the beam energy was altered iteratively until the best match between computed and measured relative activities of the stack of disks was obtained. The main advantage of this method is that it does not require the comparison of the activities of different isotopes of zinc arising from (p, xn) reactions in the Cu, which would require the gamma photon detector being calibrated for different energy responses. Using this technique the proton beam energy of a nominally 18 MeV standard isochronous medical cyclotron was measured as 17.49 +/- 0.04 (SD) MeV, with a precision of 0.2% CV.

Summary. Neutralizing alloantibodies (inhibitors) to factor VIII or factor IX develop in approximately 25% of patients with haemophilia A and <3% of patients with haemophilia B treated with factor concentrate. Patients with high titre inhibitors, in whom immune tolerance therapy fails, have few treatment options. Targeted anti-B-cell therapy with rituximab (chimeric anti-CD20) has been useful in several antibody-mediated autoimmune states. Case reports of rituximab treatment in small numbers of haemophilia patients with inhibitors have been inconclusive. We describe three adolescent patients with severe haemophilia and inhibitors treated with four weekly doses of rituximab, 375 mg m(-2). Treatment with rituximab was effective in reducing the inhibitor titre in two of three patients. Rituximab may be beneficial for patients with severe haemophilia and inhibitors in whom standard therapies have failed, but larger prospective studies are required to determine safety, efficacy and predictors of success.

PTH is in clinical use for the treatment of osteoporosis and is under intensive investigation for its potential in applications of tissue engineering, fracture healing, and implant integration. However, the mechanisms of its action to stimulate bone formation are still unclear. A novel bone tissue engineering model was used to elucidate basic mechanisms of PTH anabolic actions. Ectopic ossicles containing cortical bone, trabecular bone, and a hematopoietic marrow were generated from implanted bone marrow stromal cells (BMSC). One week after implantation, nude mice were administered PTH or vehicle for 1 week (group 1), 3 weeks (group 2), or 7 weeks (group 3). Another group was also treated for 3 weeks, initiated 12 weeks after implantation (group 4). Micro-radiography and histomorphometry revealed increased marrow cellularity in group 1 PTH-treated ossicles, increased bone in group 2 PTH-treated ossicles, and similar amounts of bone in both group 3 and 4 ossicles regardless of treatment. Incidence of phosphate mineral and phosphate mineral to hydroxyproline ratio via Raman spectroscopy were significantly higher after 3 weeks versus 1 week of PTH treatment, but there was no difference between PTH- and vehicle-treated ossicles. Early events of PTH action in group 1 ossicles and the effects of a single injection of PTH on 1- and 2-week-old ossicles were evaluated by Northern blot analysis. Osteocalcin (OC) mRNA was increased after 1 week of intermittent PTH treatment in ossicles and calvaria but an acute injection did not alter OC mRNA. In contrast, a single injection of PTH increased matrix gamma-carboxyglutamic acid protein (MGP) mRNA in 2-week-old ossicles. Differential and temporal-dependent effects of PTH on OC and MGP suggest at the molecular level, that PTH acts to inhibit osteoblast mineralization. However, this does not translate into tissue level alterations. These data indicate that anabolic actions of PTH in ectopic ossicles are temporally dependent on the BMSC implanted and suggest that cell implantation strategies are particularly responsive to PTH.

OBJECTIVE: To compare bone mineral measurements obtained by use of dual-energy x-ray absorptiometry (DEXA), peripheral quantitative computed tomography (pQCT), and chemical-physical analyses and determine effects of age and femur size on values obtained for the various techniques. SAMPLE POPULATION: Femurs obtained from 15 juvenile and 15 adult large-breed dogs. PROCEDURE: n each femur, 7 regions of interest were examined by use of DEXA to measure the bone mineral content (BMC) and bone mineral density (BMD), and 5 were examined by use of pQCT to measure BMD. Among these, 1 region was examined by both noninvasive methods and an invasive method. Volume of the femur was determined by water displacement. Volumetric bone density (VBD) was calculated. Calcium (Ca), phosphorus (P), total Ca, and total P contents were determined. RESULTS: DEXA- and pQCT-derived results revealed that all values increased with age in juvenile dogs. In adults, VBD and pQCT-derived BMD decreased significantly and DEXA-derived BMD increased with increasing femur length.The pQCT-derived BMD correlated well with VBD and Ca content, whereas DEXA-derived BMC was strongly correlated with Ca content. In juveniles, values correlated regardless of the technique used, whereas in adult dogs, DEXA-derived BMD did not correlate with pQCT-derived BMD, Ca concentration, or VBD unless data were adjusted on the basis of femur length. CONCLUSIONS AND CLINICAL RELEVANCE: DEXA-derived BMD adjusted for femur length yields approximately the same percentage variability in VBD as for pQCT-derived BMD. However, pQCT-derived BMD is still more sensitive for determining variability BMD in Ca concentration, compared with DEXA-derived BMD adjusted for femur length.

In the present study, we focused on the relationship of intra-abdominal visceral fat (VF) or subcutaneous fat (SF) mass to serum leptin levels, and also on the relationship of leptin to serum lipid and lipoprotein concentration. Subjects with obesity (26 men, 26 women) were recruited for this study. We obtained helical CT scans with a tube current of 150 mA, voltage of 120 kV and 2:1 pitch (table speed in relation to slice thickness), starting at the upper edge of the liver and continuing to the pelvis. The intra-abdominal visceral fat (VF) volume was measured by drawing a line within the muscle wall surrounding the abdominal cavity. The abdominal SF volume was calculated by subtracting the VF volume from the total abdominal fat volume. By comparison, the abdominal VF and SF areas were determined at the umbilical level by the established slice-by-slice CT scanning technique. We found: 1) abdominal SF mass, either as volume or area, was a more important determinant of serum leptin than was VF mass; 2) among TC, TG, HDL-C and LDL-C, only TG had a positive correlation to serum leptin levels in men, whereas in women no lipid parameters had any relationship with leptin; and 3) VF mass had a positive correlation to serum TC and TG in men, whereas SF did not.The present study provides considerable evidence on the relationship between abdominal fat mass and serum leptin, and shows that the relationships between serum leptin and serum lipids and lipoproteins are not straightforward. We also suggest that fat area measured by conventional CT is a better indicator than its corresponding volume assessed by helical CT, based on the present results showing its closer association to serum lipids.

OBJECTIVE: To evaluate bone mineral density considering its distribution, fractional quantitative computed tomography (fQCT) was designed and verified. METHODS: Quantitative computed tomography (QCT) was performed at 64 areas in 10 swine long bones. Fractional quantitative computed tomography was measured at the identical areas as the proportion of pixels showing a bone density higher than 130 mg/mL equivalent. All target areas were extracted and incinerated to measure apparent ash bone density. Based on standard references, the accuracy and precision of fQCT were evaluated and the results were compared with conventional QCT results. RESULTS: The correlation coefficient between fQCT and apparent ash bone density was 0.843 (P < 0.0001). The fQCT showed good correlation with volume fraction (r = 0.88, P < 0.0001). The coefficient of variation of fQCT was 0.42%. The fQCT revealed higher accuracy and precision than the results of QCT. CONCLUSION: Fractional quantitative computed tomography was designed and verified as a reliable method to measure bone mineral density.

BACKGROUND: Body composition differs between African American (AA) and white women, and the resting metabolic rate (RMR) is likely to be lower in AA women than in white women. OBJECTIVE: We tested 2 hypotheses: that AA women have a greater proportion of low-metabolic-rate skeletal muscle (SM) and bone than do white women and that between-race musculoskeletal differences are a function of body weight. DESIGN: Hypothesis 1 was tested by comparing SM, bone, adipose tissue, and high-metabolic-rate residual mass across 22 pairs of matched AA and white women. Magnetic resonance imaging and dual-energy X-ray absorptiometry were used to partition weight into 4 components, and RMR was both calculated from tissue-organ mass and measured. Hypothesis 2 was evaluated by measuring SM, bone, fat, and residual mass in 521 AA and white women with the use of dual-energy X-ray absorptiometry alone. RESULTS: Hypothesis 1: AA women had greater SM (+/- SD group difference: 1.52 +/- 2.48 kg; P < 0.01) and musculoskeletal mass (1.72 +/- 2.66 kg; P < 0.01) than did white women. RMR calculated from body composition and measured RMR did not differ; RMR estimated by both approaches tended to be lower ( approximately 160 kJ/d) in AA women than in white women. Hypothesis 2: SM was significantly correlated with weight, height, age, and race x weight interaction; greater SM in the AA women was a function of body weight. CONCLUSIONS: Lower RMRs in AA women than in white women are related to corresponding differences in the proportions of heat-producing tissues and organs, and these race-related body-composition differences increase as a function of body weight.

The study was done in Starbro chicks aged 1 to 50 days. Two chicks were collected every day and the femoral bones were removed. Altogether, 200 bones were studied. The material was divided into 5 age groups (I to V). Compact and spongy bone, bone marrow and articular cartilage were sampled. Lipids were extracted according to Folch et al. Total lipids were measured spectrophotometrically. Gas chromatography was used to study the content of individual fatty acids. Calcium (Ca), phosphorus (P), magnesium (Mg) and zinc (Zn) levels were determined using atomic absorption spectrometry (Philips PU 9100X), while fluorine content was studied with gas chromatography. As the distribution of the results deviated from normal, non-parametric Kruskal-Wallis and median tests were used. Correlations were studied with Spearman's Rs coefficients. Computations were done with Statistica 5.0 (StatSoft) software and the level of significance was taken as p < 0.05. Statistically significant differences in the fatty acid profile (Tab. 1) and content of elements (Tab. 2) were found. The content of fatty acids, calcium and fluorine correlated with age. Fatty acids with the highest content in bone tissues were C18:1, C16:0, C18:2 and C18:0. The highest content of fatty acids was found in bone marrow and the lowest in articular cartilage. Several correlations were revealed between individual fatty acids and elements (Tab. 3, 4). The following conclusions were drawn: 1) The fatty acid profile in compact and spongy bone, bone marrow and articular cartilage changed according to age of chicks; 2) Content of calcium, phosphorus, magnesium, zinc and fluoride correlated with age; 3) Oleic (C18:1), palmitic (C16:0), linoleic (C18:2), stearic (C18:0) and arachidonic acid (C20:4) accounted for the majority of the fatty acid pool; 4) Correlations in the content of fatty acids and elements were noted between bone structures. Fatty acids appear to play an important role in the metabolism of bone tissues, particularly in mineralization processes.

RATIONALE AND OBJECTIVES: This in vitro study was designed to improve the accuracy of coronary calcium mass measurement from computed tomography (CT) images by developing threshold-based calcium CT number correction and thin-slice spiral techniques. MATERIALS AND METHODS: A cardiac CT phantom containing simulated calcified cylinders of known calcium density was scanned with sequential 4 x 2.5-, spiral 16 x 1.5-, and spiral 16 x 0.75-mm collimation on 4- and 16-detector row CT scanners. The images obtained from the spiral scans were reconstructed in various slice widths. The calcified cylinders were imaged and their mean CT number and size were measured at thresholds ranging from 50 to 390 Hounsfield unit. The calcium mass measured was compared with the actual value to determine errors, and threshold-based correction factors were derived to minimize the errors. RESULTS: The minimum amount of measurable calcium in 1-mm cylinder was 0.3 mg at the 16 X 1.5-mm protocol and 0.2 mg at the 16 x 0.75-mm protocol. Compared with 2.5-mm sequential protocol, thin-slice spiral protocols yielded a higher radiation exposure and lower or similar image noise levels. The error in calcium mass after correction was significantly smaller than that in measured mass (P <.0001) and was consistent between the imaging protocols (P =.49). The accuracy of mass measurements was clearly improved by using thin-slice imaging protocols especially in 200-mg/cm3 calcium density (P <.0001). CONCLUSION: The accuracy of calcium mass CT measurement can be improved by threshold-based calcium CT number correction and thin collimation spiral techniques.

This paper describes a statistical image reconstruction method for x-ray CT that is based on a physical model that accounts for the polyenergetic x-ray source spectrum and the measurement nonlinearities caused by energy-dependent attenuation. Unlike our earlier work, the proposed algorithm does not require pre-segmentation of the object into the various tissue classes (e.g., bone and soft tissue) and allows mixed pixels. The attenuation coefficient of each voxel is modelled as the product of its unknown density and a weighted sum of energy-dependent mass attenuation coefficients. We formulate a penalized-likelihood function for this polyenergetic model and develop an iterative algorithm for estimating the unknown density of each voxel. Applying this method to simulated x-ray CT measurements of objects containing both bone and soft tissue yields images with significantly reduced beam hardening artefacts relative to conventional beam hardening correction methods. We also apply the method to real data acquired from a phantom containing various concentrations of potassium phosphate solution. The algorithm reconstructs an image with accurate density values for the different concentrations, demonstrating its potential for quantitative CT applications.

STUDY DESIGN Autogenous bone marrow stromal-derived osteoblasts-porous calcium phosphate ceramic composites were constructed in vitro under cell culture for 48 hours and implanted as a bone graft substitute for lumbar intervertebral spinal fusion in rabbits.OBJECTIVES To evaluate the efficacy of autogenous bone marrow stromal-derived osteoblasts-porous calcium phosphate ceramic composites as an alternative to autogenous graft materials in a lumbar interbody spinal fusion model.SUMMARY OF BACKGROUND DATA Bone marrow contains a population of rare progenitor cells capable of differentiating into bone, cartilage, muscle, tendon, and other connective tissues. These cells can be induced and differentiated into osteogenic osteoblasts with addition of osteogenic supplements. Combining bone marrow stromal-derived osteoblasts with porous ceramics gave rise to bone tissue in subcutaneous sites and repaired critical size segmental femoral defects. Little work has been done in the spine to assess fusion rates and associated biomechanical characteristics.METHODS Five experimental groups were evaluated: sham operation (Group I); porous calcium phosphate ceramics alone (Group II); autogenous tricortical iliac crest (Group III); bone marrow stromal-derived osteoblasts-calcium phosphate ceramic composites (Group IV); bone marrow stromal-derived osteoblasts-calcium phosphate ceramic composites with rhBMP-2 (Group V). All rabbits were killed 12 weeks after surgery, and the spinal fusion segments underwent the evaluation of gross inspection, manual palpation, radiography, computed tomography, nondestructive biomechanical testing, and histologic analysis.RESULTS Successful spinal fusion was achieved by manual palpation in 100%(6/6) of animals in Group IV and Group V, 66.7%(4/6) in Group III, 50%(3/6) in Group II, and 0%(0/6) in Group I. Radiographic studies showed that minimal disc height loss was observed with ceramic blocks than with autograft. Biomechanical testingconfirmed that spines from Group IV and Group V were statistically significantly stiffer in flexion, extension, left and right bending, and left and right torsion than Group III and Group II. Histologic analysis demonstrated a qualitative increase of bone formation in fusion mass in Group IV and Group V versus all other groups. The size of fusion mass and the stiffness of fusion segments were greatest in Group V.CONCLUSION The results indicate that bone marrow stromal-derived osteoblasts-calcium phosphate ceramic composites may provide an alternative to autogenous graft materials for lumbar interbody spinal fusion. Adding recombinant human bone morphogenetic protein-2 into the composites may reinforce the biomechanical stiffness for spinal fusion segments. Porous calcium phosphate ceramics alone were not suitable as a bone graft substitute for lumbar interbody spinal fusion.