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Screening for lung cancer.

The lethality of lung cancer is related to the advanced stage at diagnosis. Initial studies have demonstrated that screening computed tomography (CT) is effective in diagnosing lung cancer at an earlier stage when compared with current clinical practice, however the best clinical approach for screening detected nodules has to be defined. The population to be identified as high risk should be over 50 years of age and should have smoked at least one pack/day for 20 years. CT protocols should use multidetector CT, low dose and a 2.5 reconstruction interval. Diagnostic workup on detected nodules should be designed according to size and consider CT at 3 or 12 months to evaluate doubling time, CT enhancement, PET/CT and/or FNAB or VATS. The prevalence of lung cancer in the screened population is 1.1%-2.7%, and the incidence is 0.2%-1.1%. Eighty-one percent of cancers are diagnosed in stage I. The percentage of surgery performed for benign lesions ranges from 21% to 55%. In our series, the overall mortality rate was 3.2% in 5 years. The results of randomized clinical studies, when available, will assess the real efficacy of CT in reducing lung cancer related mortality.

Aged↗

Volume CT with a flat-panel detector on a mobile, isocentric C-arm: pre-clinical investigation in guidance of minimally invasive surgery.

A mobile isocentric C-arm (Siemens PowerMobil) has been modified in our laboratory to include a large area flat-panel detector (in place of the x-ray image intensifier), providing multi-mode fluoroscopy and cone-beam computed tomography (CT) imaging capability. This platform represents a promising technology for minimally invasive, image-guided surgical procedures where precision in the placement of interventional tools with respect to bony and soft-tissue structures is critical. The image quality and performance in surgical guidance was investigated in pre-clinical evaluation in image-guided spinal surgery. The control, acquisition, and reconstruction system are described. The reproducibility of geometric calibration, essential to achieving high three-dimensional (3D) image quality, is tested over extended time scales (7 months) and across a broad range in C-arm angulation (up to 45 degrees), quantifying the effect of improper calibration on spatial resolution, soft-tissue visibility, and image artifacts. Phantom studies were performed to investigate the precision of 3D localization (viz., fiber optic probes within a vertebral body) and effect of lateral projection truncation (limited field of view) on soft-tissue detectability in image reconstructions. Pre-clinical investigation was undertaken in a specific spinal procedure (photodynamic therapy of spinal metastases) in five animal subjects (pigs). In each procedure, placement of fiber optic catheters in two vertebrae (L1 and L2) was guided by fluoroscopy and cone-beam CT. Experience across five procedures is reported, focusing on 3D image quality, the effects of respiratory motion, limited field of view, reconstruction filter, and imaging dose. Overall, the intraoperative cone-beam CT images were sufficient for guidance of needles and catheters with respect to bony anatomy and improved surgical performance and confidence through 3D visualization and verification of transpedicular trajectories and tool placement. Future investigation includes improvement in image quality, particularly regarding x-ray scatter, motion artifacts and field of view, and integration with optical tracking and navigation systems.

Algorithms↗

Properties of preprocessed sinogram data in x-ray computed tomography.

The accurate determination of x-ray signal properties is important to several computed tomography (CT) research and development areas, notably for statistical reconstruction algorithms and dose-reduction simulation. The most commonly used model of CT signal formation, assuming monoenergetic x-ray sources with quantum counting detectors obeying simple Poisson statistics, does not reflect the actual physics of CT acquisition. This paper describes a more accurate model, taking into account the energy-integrating detection process, nonuniform flux profiles, and data-conditioning processes. Methods are developed to experimentally measure and theoretically calculate statistical distributions, as well as techniques to analyze CT signal properties. Results indicate the limitations of current models and suggest improvements for the description of CT signal properties.

Algorithms↗

Artificial spine fractures: detection with helical and conventional CT.

PURPOSE: To compare the accuracy of detection of artificial spine fractures with helical computed tomography (CT) versus conventional CT. MATERIALS AND METHODS: Twenty-six motion segments from 15 human cadaver thoracolumbar spines were imaged with helical and conventional CT both before and after fractures were artificially induced. The vertebrae were scanned with different collimations, reconstruction indexes, and exposure doses. A total of 900 images were analyzed by four radiologists, and a receiver operating characteristic (ROC) analysis was performed. RESULTS: ROC analysis showed a large area under the curve for conventional CT (0.913) than for helical CT (0.844) when 3-mm collimation was used. The ability to detect fractures with helical CT increased when collimation was decreased and exposure dose was increased. CONCLUSION: Conventional CT allows more accurate detection of artificial spine fractures than does helical CT. Helical CT requires thinner collimation for fracture detection comparable with that of conventional CT.

Cadaver↗

[The results of cytogenetic survey in liquidators of the Chernobyl nuclear accident].

The article represents results of long cytogenetic survey among liquidators of Chernobyl accident. The parameters studied are frequency of unstable chromosomal aberrations and frequency of symmetrical translocations. The authors show that, in spite of long term after irradiation, average frequency of cells with dicentrics and centric fusions (unstable chromosomal aberrations) remains relatively high. Discussion includes possible use of cytogenetic methods in reconstruction of absorbed radiation doses in many years after exposure.

Chromosome Aberrations↗

[Management of radiation injuries--new organization, new guidelines].

The medical management of radiation accident victims is based on a rapid assessment and reconstruction of the radiation dose and quality combined with prompt, targeted treatment efforts performed at specialized medical units. To facilitate such medical emergency preparedness in Sweden, the National Board of Health and Welfare has recently established a new Centre for Radiation Medicine, located at the Karolinska institute in Stockholm. Among the tasks of this centre are also to contribute with health care information, education, advice and carry out research activities in areas related to medical effects of ionizing radiation. A close collaboration is being established with the Swedish Radiation Protection Authority and also with various other national and international bodies. The initiation of the Centre for Radiation Medicine comes in parallel with a rapid development of the understanding of and treatment options for patients acquiring an acute radiation syndrome, mainly due to improved diagnostic procedures combined with novel therapeutic options, such as stem cell transplantation and cytokine administration.

Academies and Institutes↗

Evaluation of the reconstruction of seed positions from stereo and orthogonal radiographs for routine radiotherapy planning.

Brachytherapy, which refers to short-distance treatment via implanted sources, requires an accurate knowledge of the dose distribution in the implant volume. A critical step in the determination of the dose distribution involves an accurate reconstruction of seed positions. Stereo and orthogonal radiographs offer two distinct imaging techniques for determining the seed positions in the implant volume. This work is an attempt to study the effects of random errors associated with the three-dimensional reconstruction of a two-plane seed implant from stereo and orthogonal radiographs. The uncertainty in coordinates is expressed as the standard deviation of the measurements. To assess the geometric accuracy of the stereo and orthogonal methods, the computer-reconstructed coordinates of each seed are compared with the measured and manually calculated coordinates. The uncertainties in the coordinates and relative positions of seeds are also estimated by considering the propagation of errors in the reconstructed parameters. The isodose contours surrounding the implant are obtained for both methods. Using a sonic digitizer to input the data, it was found that seed coordinates and relative seed positions can be obtained satisfactorily from stereo radiographs. The uncertainties were compared with the values reported in the literature. Suggestions are made to reduce the uncertainties in the reconstruction of coordinates with the stereo method.

Brachytherapy↗

A new approach to in vitro comparisons of antibiotics in dynamic models: equivalent area under the curve/MIC breakpoints and equiefficient doses of trovafloxacin and ciprofloxacin against bacteria of similar susceptibilities.

Time-kill studies, even those performed with in vitro dynamic models, often do not provide definitive comparisons of different antimicrobial agents. Also, they do not allow determinations of equiefficient doses or predictions of area under the concentration-time curve (AUC)/MIC breakpoints that might be related to antimicrobial effects (AMEs). In the present study, a wide range of single doses of trovafloxacin (TR) and twice-daily doses of ciprofloxacin (CI) were mimicked in an in vitro dynamic model. The AMEs of TR and CI against gram-negative bacteria with similar susceptibilities to both drugs were related to AUC/MICs that varied over similar eight-fold ranges [from 54 to 432 and from 59 to 473 (microg . h/ml)/(microg/ml), respectively]. The observation periods were designed to include complete bacterial regrowth, and the AME was expressed by its intensity (the area between the control growth in the absence of antibiotics and the antibiotic-induced time-kill and regrowth curves up to the point where viable counts of regrowing bacteria equal those achieved in the absence of drug [IE]). In each experiment monoexponential pharmacokinetic profiles of TR and CI were simulated with half-lives of 9.2 and 4.0 h, respectively. Linear relationships between IE and log AUC/MIC were established for TR and CI against three bacteria: Escherichia coli (MIC of TR [MICTR] = 0.25 microg/ml; MIC of CI [MICCI] = 0.12 microg/ml), Pseudomonas aeruginosa (MICTR = 0.3 microg/ml; MICCI = 0.15 microg/ml), and Klebsiella pneumoniae (MICTR = 0.25 microg/ml; MICCI = 0.12 microg/ml). The slopes and intercepts of these relationships differed for TR and CI, and the IE-log AUC/MIC plots were not superimposed, although they were similar for all bacteria with a given antibiotic. By using the relationships between IE and log AUC/MIC, TR was more efficient than CI. The predicted value of the AUC/MIC breakpoint for TR [mean for all three bacteria, 63 (microg . h/ml)/(microg/ml)] was approximately twofold lower than that for CI. Based on the IE-log AUC/MIC relationships, the respective dose (D)-response relationships were reconstructed. Like the IE-log AUC/MIC relationships, the IE-log D plots showed TR to be more efficient than CI. Single doses of TR that are as efficient as two 500-mg doses of CI (500 mg given every 12 h) were similar for the three strains (199, 226, and 203 mg). This study suggests that in vitro evaluation of the relationships between IE and AUC/MIC or D might be a reliable basis for comparing different fluoroquinolones and that the results of such comparative studies may be highly dependent on their experimental design and datum quantitation.

Anti-Infective Agents↗

A three-film technique for reconstruction of radioactive seed implants.

Computer dose calculations for interstitial implants of radioactive seeds require a knowledge of the spatial coordinates of each seed in the implant. These coordinates are usually constructed from the seed images on either an orthogonal or a stereo pair of radiographs. Such a procedure, however, requires that each seed can be identified on each film. We have developed a computer algorithm which computes the locations of the seeds from a set of two stereo and one AP radiographs, even when seed identities on all films are indeterminable. This is done by means of a ray tracing technique. Under ideal conditions the projections from the three films uniquely define all seed locations. Under clinical conditions, however, where digitizing uncertainties and patient movement are inevitable, the algorithm must determine the most likely set of seed locations from the larger set of all possible seed locations. The criteria for making this selection, as well as clinical examples, are presented.

Brachytherapy↗

Bayesian methods for chromosome dosimetry following a criticality accident.

Radiation doses received during a criticality accident will be from a combination of fission spectrum neutrons and gamma rays. It is desirable to estimate the total dose, as well as the neutron and gamma doses. Present methods for dose estimation with chromosome aberrations after a criticality accident use point estimates of the neutron to gamma dose ratio obtained from personnel dosemeters and/or accident reconstruction calculations. In this paper a Bayesian approach to dose estimation with chromosome aberrations is developed which allows the uncertainty of the dose ratio to be considered. Posterior probability densities for the total and the neutron and gamma doses were derived.

Bayes Theorem↗

Accurate two-dimensional IMRT verification using a back-projection EPID dosimetry method.

The use of electronic portal imaging devices (EPIDs) is a promising method for the dosimetric verification of external beam, megavoltage radiation therapy-both pretreatment and in vivo. In this study, a previously developed EPID back-projection algorithm was modified for IMRT techniques and applied to an amorphous silicon EPID. By using this back-projection algorithm, two-dimensional dose distributions inside a phantom or patient are reconstructed from portal images. The model requires the primary dose component at the position of the EPID. A parametrized description of the lateral scatter within the imager was obtained from measurements with an ionization chamber in a miniphantom. In addition to point dose measurements on the central axis of square fields of different size, we also used dose profiles of those fields as reference input data for our model. This yielded a better description of the lateral scatter within the EPID, which resulted in a higher accuracy in the back-projected, two-dimensional dose distributions. The accuracy of our approach was tested for pretreatment verification of a five-field IMRT plan for the treatment of prostate cancer. Each field had between six and eight segments and was evaluated by comparing the back-projected, two-dimensional EPID dose distribution with a film measurement inside a homogeneous slab phantom. For this purpose, the y-evaluation method was used with a dose-difference criterion of 2% of dose maximum and a distance-to-agreement criterion of 2 mm. Excellent agreement was found between EPID and film measurements for each field, both in the central part of the beam and in the penumbra and low-dose regions. It can be concluded that our modified algorithm is able to accurately predict the dose in the midplane of a homogeneous slab phantom. For pretreatment IMRT plan verification, EPID dosimetry is a reliable and potentially fast tool to check the absolute dose in two dimensions inside a phantom for individual IMRT fields. Film measurements inside a phantom can therefore be replaced by EPID measurements.

Algorithms↗

Estimating exposure and dose to characterize health risks: the role of human tissue monitoring in exposure assessment.

Exposure assessment is an integral part of health risk characterization. Exposure assessments typically address three critical aspects of exposure: the number of people exposed to the environmental toxicant, at specific concentrations, for the time period of interest; the resulting dose; and the relative contribution of important sources and pathways to exposure/dose. Because historically both "point-of-contact" measurements and information about dose and related pharmacokinetic processes have been lacking, exposure assessments have had to rely on construction of "scenarios" to estimate exposure and dose. This could change, however, as advances in development of biologic markers of exposure and dose make it possible to measure and interpret toxicant concentrations in accessible human tissues. The increasing availability of "biomarkers," coupled with improvements in pharmacokinetic understanding, present opportunities to estimate ("reconstruct") exposure from measurements of dose and knowledge of intake and uptake parameters. Human tissue monitoring, however, is not a substitute for more traditional methods of measuring exposure, but rather a complementary approach. A combination of exposure measurements and dose measurements provides the most credible scientific basis for exposure assessment.

Biomarkers↗

Comparison of immediate and delayed free TRAM flap breast reconstruction in patients receiving postmastectomy radiation therapy.

Tumor pathologic features and the extent of nodal involvement dictate whether radiation therapy is given after mastectomy for breast cancer. It is generally well accepted that radiation negatively influences the outcome of implant-based breast reconstruction. However, the long-term effect of radiation therapy on the outcome of breast reconstruction with the free transverse rectus abdominis myocutaneous (TRAM) flap is still unclear. For patients who need postmastectomy radiation therapy, the optimal timing of TRAM flap reconstruction is controversial. This study compares the outcome of immediate and delayed free TRAM flap breast reconstruction in patients who received postmastectomy radiation therapy. All patients at The University of Texas M. D. Anderson Cancer Center who received postmastectomy radiation therapy and who also underwent free TRAM flap breast reconstruction between January of 1988 and December of 1998 were included in the study. Patients who received radiation therapy before delayed TRAM flap reconstruction were compared with patients who underwent immediate TRAM flap reconstruction before radiation therapy. Early and late complications were compared between the two groups. Early complications included vessel thrombosis, partial or total flap loss, mastectomy skin flap necrosis, and local wound-healing problems, whereas late complications included fat necrosis, volume loss, and flap contracture of free TRAM breast mounds. Late complications were evaluated at least 1 year after the completion of radiation therapy for patients who had delayed reconstruction and at least 1 year after reconstruction for patients who had immediate reconstruction. During the study period, 32 patients had immediate TRAM flap reconstruction before radiation therapy and 70 patients had radiation therapy before TRAM flap reconstruction. Mean follow-up times for the immediate reconstruction and delayed reconstruction groups were 3 and 5 years, respectively. The mean radiation dose was 50 Gy in the immediate reconstruction group and 51 Gy in the delayed reconstruction group. One complete flap loss occurred in the delayed reconstruction group, and no flap loss occurred in the immediate reconstruction group. The incidence of early complications did not differ significantly between the two groups. However, the incidence of late complications was significantly higher in the immediate reconstruction group than in the delayed reconstruction group (87.5 percent versus 8.6 percent; p = 0.000). Nine patients (28 percent) in the immediate reconstruction group required an additional flap to correct the distorted contour from flap shrinkage and severe flap contraction. These findings indicate that, in patients who are candidates for free TRAM flap breast reconstruction and need postmastectomy radiation therapy, reconstruction should be delayed until radiation therapy is complete.

Breast Neoplasms↗

Some aspects of EPR dosimetry of liquidators.

Doses of few hundred liquidators were reconstructed using EPR dosimetric technique, developed and routinely used in SCRM. Both cumulative and accidental dose values were determined. Obtained results are analyzed and discussed.

Dental Enamel↗

The effects of low, medium and high dose aspirin on intimal proliferation in autologous vein grafts used for arterial reconstruction.

Bilateral femoral vein grafts were implanted in 47 adult mongrel dogs to determine the effects of aspirin on intimal hyperplasia. The animals were fed a commercially-prepared 2% cholesterol diet before and for 6 weeks following operation. Twelve animals served as the controls while the remaining animals were divided into three groups receiving low, medium, and high dose aspirin. Eleven animals received 75 mg of aspirin daily, 11 animals were fed 225 mg of aspirin daily and the remaining 13 animals received 650 mg of aspirin daily. A coagulation profile was carried out before operation and at 2, 4 and 6 weeks following operation. The grafts were harvested at 6 weeks and intimal thickness was measured with a Zeiss computerized interactive image-analyzing system. The prothrombin time, partial thromboplastin time, and platelet count were unchanged in all animals. The bleeding time was prolonged in animals receiving aspirin (P less than 0.02). Intimal thickness measured 4 +/- 0.2 microns before implantation and increased at 6 weeks to 39 +/- 5 microns in the control group. Aspirin failed to reduce intimal hyperplasia. Intimal thickness measured 37 +/- 2 microns in those animals receiving 75 mg of aspirin daily, 35 +/- 3 microns after a daily dose of 225 mg of aspirin and 51 +/- 4 microns in the high dose group receiving 650 mg of aspirin daily. Our data indicates that aspirin fails to reduce intimal proliferation in canine vein grafts which suggests that alternative or combined drug therapy may be necessary to reduce the incidence of late graft failure.

Animals↗

Whole-body low-dose multidetector row-CT in the diagnosis of multiple myeloma: an alternative to conventional radiography.

OBJECTIVE: The goal of this study was to establish the feasibility of a low-dose whole-body multidetector row-CT (MDCT) protocol in the diagnosis of multiple myeloma (MM), as an alternative to conventional X-ray imaging, which is currently still state-of-the-art in these patients, with emphasis on the comparison of image resolution on axial and multiplanar reformatted (MPR) scans and reduction of radiation dose. MATERIAL AND METHODS: 100 patients with known MM, or monoclonal gammopathy of unknown significance (MGUS) underwent unenhanced whole-body MDCT on a 16-slice scanner in a randomised fashion, using a 16 x 1.5 mm collimation and four different energy parameters (40, 50, 60 and 70 mAs). Three different reconstruction algorithms were used in every patient (B40f, B50f and B60f kernel). CT scans were reviewed independently by two radiologists, with regard to correct classification into one of the three known MM stages, and recognition of fracture risk. Thereafter, axial and MPR images were evaluated in consensus by both readers, with respect to image resolution. Diagnosis of osteolytic lesions was performed on the basis of axial and multiplanar reformatted images, whereas the assessment of spinal misalignment and fracture was done only on MPR images. The distribution of image resolution categories (very good, good, sufficient, insufficient for diagnosis) was evaluated depending on following parameters: current time product, patient's weight, bone density and reconstruction algorithm. The effective radiation dose was determined with the aid of an anthropomorphic Alderson Rando-Phantom, using a tube current time product of 40 mAs, and then extrapolating it on all current time products applied in this study on a commercially available software program WinDose (Institute of Medical Physics, Erlangen, Germany). RESULTS: In all 100 patients, image resolution was diagnostic, regardless of scanning parameters, enabling correct classification of multiple myeloma patients. Image quality of MPR images was either equal or inferior to correspondent axial images in the delineation of smaller lytic lesions, because of the use of non-isotropic voxel size. However, they proved accurate in diagnosing fracture and spine misalignment. A strong dependency of image resolution on bone density was observed, with reduced quality in patients with either diffuse skeleton infiltration or concurrent osteoporosis. Spatial resolution was also dependent on the reconstruction algorithm and energy level (mAs) used, as well as on patient's weight, but their influence was low within the given ranges. A middle-frequency reconstruction algorithm (B50f kernel) proved beneficial for all energy protocols. The interobserver agreement was excellent (kappa = 0.95) for classification of MM-patients. Effective radiation dose of MDCT calculated at a tube current time product of 40 mAs was 1.7-fold higher than the mean radiation dose of conventional X-ray (4.1 mSv versus 2.4 mSv). DISCUSSION: Our study shows that whole-body low-dose MDCT investigational protocols are appropriate for the diagnosis of lytic bone changes and for assessment of fracture risk in multiple myeloma patients, representing a serious alternative to current standards.

Aged↗

The importance of three-dimensional brachytherapy treatment planning for nasopharyngeal carcinoma.

High dose rate (HDR) intracavitary brachytherapy is now more frequently incorporated into treatment programmes for patients with persistent and recurrent nasopharyngeal carcinoma (NPC). However, many centres still employ two-dimensional (2-D) image reconstruction for applicators with a three-dimensional (3-D) orientation. In this study, we introduced the use of a mobile modified Nucletron reconstruction box inside the brachytherapy suite for image reconstruction and quality assurance. Three-dimensional reconstruction of the applicators' configurations proved possible and the dose distributions generated by the 2-D and 3-D image reconstructions could be compared. Thirty-one applications were included in this part of the analysis. The results showed that, based on the 2-D planning method, the reference doses were under-prescribed by 1%-10% in all except one patient, whose dose was over-prescribed by 3%. The evaluated doses to the floor of the sphenoid, which was shown to be significant for subsequent local control, was shown to be underestimated by up to 19% or overestimated by 18%, with an average of 5.9% dose underestimation. With this system, the reliability of the anchoring techniques was verified by posttherapy radiographs. Any catheter displacement of more than 1 mm was counted as a failure. Nine of the 43 verified applications were classified as failures, although six of nine catheter displacements measured < or = 2.5 mm. We recommend the routine use of a modified reconstruction box for 3-D image reconstruction for dose calculation and prescription in the treatment of NPC with HDR intracavitary brachytherapy. Quality assurance programmes should be included as an integral part of any HDR treatment; their importance cannot be overemphasized.

Brachytherapy↗

The effect of geometric errors in the reconstruction of iridium-192 seed implants.

In the treatment of tumors using interstitial implants of radioactive seeds, the accuracy of computed dose distributions depends upon the accuracy with which the three-dimensional source geometries are reconstructed from radiographs of the implants. The effect of geometric reconstruction errors in iridium-192 seed implants were studied, using tumor dose as the measure. Tumor dose was defined as the average dose around the periphery of the treatment volume. Three ideal mathematical implants and five actual patient implants were used. The implants were distorted by randomly moving a specified number of seeds a specified distance. Tumor doses were directly calculated for the ideal implants. For the actual implants, isodose distributions were plotted and were read by a radiotherapist. For both types of implants, percentage errors in the tumor doses were calculated for the distorted reconstructions relative to the correct reconstructions. It was found that the tumor dose was accurate to within 5% if all the seeds were reconstructed to within 0.5 cm of their actual positions. Furthermore, up to 5% of the seeds could be mismatched between films, or otherwise incorrectly reconstructed, with position errors as large as 20 cm, and not change the tumor dose by more than 5%.

Brachytherapy↗