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PubMed2006

Developments in and experience of kilovoltage X-ray cone beam image-guided radiotherapy.

This paper offers a realistic review of kilovoltage X-ray cone beam tomography integrated with the treatment machine for image-guided radiotherapy in the light of experience taking a commercial system from prototype development into clinical use. It shows that key practicalities cannot be ignored, in particular the regular characterization of mechanical flex during gantry rotation, the mapping of defects in flat panel image transducers and their response to X-ray exposure. The number of X-ray projections and the doses required for clinically useful cone beam reconstruction at different therapy sites are considered in the context of imaging that is fit for purpose. Three roles for cone beam tomography in radiotherapy are identified: patient setup in three dimensions (3D), where even low dose cone beam tissue detail is superior to megavoltage imaging; disease targeting where, despite wide field scatter and slow scanning, it is possible to generate images that are suitable for tumour delineation even at challenging sites; adaptive treatment planning, where calibrated cone beam images have been shown to provide sufficient target detail to support "plan of the day" selection and have the potential for planning with bulk corrections. With frequent use in mind, the need to limit patient dose during setup, yet maximize much needed image quality in the target zone, is considered. Finally, it is noted that the development of cone beam tomography for radiotherapy is far from complete, with X-ray source, image transducer, reconstruction algorithms and techniques for image profile collection still being researched.

Humans↗
PubMed2005

IMRT for adjuvant radiation in gastric cancer: a preferred plan?

PURPOSE: To assess the potential advantage of intensity-modulated radiotherapy (IMRT) over conformal planning for postoperative adjuvant radiotherapy in patients with gastric carcinoma. METHODS AND MATERIALS: Twenty patients who had undergone treatment planning with conformal beam arrangements for 4500 cGy adjuvant radiotherapy between 2000 and 2001 underwent repeat planning using IMRT techniques. Conformal five-field plans were compared with seven- to nine-field coplanar sliding-window IMRT plans. For each patient, the cumulative dose-volume histograms and organ-dose summaries (without distributions or digitally reconstructed radiographs) were provided to two independent, "blinded" GI radiation oncologists. The oncologists indicated which plan provided better planning target volume coverage and critical organ sparing, any safety concerns with either plan, and which plan they would choose to treat the patient. RESULTS: In 18 (90%) of 20 cases, both oncologists chose the same plan. Cases with disagreement were given to a third "blinded" reviewer. A "preferred plan" could be determined in 19 (95%) of 20 cases. IMRT was preferred in 17 (89%) of 19 cases. In 4 (20%) of 20 IMRT plans at least one radiation oncologist had safety concerns because of the spinal cord dose (3 cases) or small bowel dose (2 cases). Of 42 ratings, IMRT was thought to provide better planning target volume coverage in 36 (86%) and better sparing of the spinal cord in 31 (74%) of 42, kidneys in 29 (69%), liver in 30 (71%), and heart in 29 (69%) of 42 ratings. The median underdose volume (1.7 vs. 4.1 cm3), maximal dose to the spinal cord (36.85 vs. 45.65 Gy), and dose to 50% of the liver (17.29 vs. 27.97), heart (12.89 vs. 15.50 Gy), and left kidney (15.50 vs. 16.06 Gy) were lower with IMRT than with the conformal plans. CONCLUSION: Compared with the conformal plans, oncologists frequently preferred IMRT plans when using dose-volume histogram data. The advantages of IMRT plans include both improved planning target volume coverage and improved sparing of critical organs. We are currently studying organ motion in the upper abdomen as a prerequisite to using IMRT for actual patient treatment.

Adult↗
PubMed1984

Intraarterial streptokinase infusion for acute popliteal and tibial artery occlusion.

Eight consecutive patients with acute thrombotic or embolic occlusion of the popliteal or tibial artery were treated with low-dose intraarterial streptokinase followed by arterial reconstructive surgery where appropriate. Three patients had acute thrombosis of a popliteal aneurysm with limb-threatening ischemia. All three were relieved of their acute ischemia by streptokinase infusion accompanied by lysis of clots in the popliteal artery outflow tract. Each patient then underwent elective popliteal aneurysm bypass. Four patients had acute embolic popliteal or tibial artery occlusion. Each was relieved of ischemic symptoms. One required surgery to remove residual clot. One patient with thrombosis of the tibioperoneal trunk did not have a decrease in symptoms with streptokinase infusion, but did experience sufficient outflow tract thrombolysis to permit construction of a tibial bypass with resultant restoration of normal circulation. Low-dose intraarterial streptokinase may be the treatment of choice for selected patients who present with thrombosis of a popliteal aneurysm with tibial vessel involvement or with embolic popliteal or tibial artery occlusion.

Acute Disease↗
PubMedDate not supplied

The effects of radiation damage on the structure of frozen hydrated HSV-1 capsids.

Radiation damage imposes stringent limits on the information content of electron micrographs of biological specimens. In this study, we have investigated its effects on frozen, hydrated specimens and three-dimensional reconstructions calculated from cryomicrographs using capsids of herpes simplex virus as a model system. Multiple-exposure series of micrographs of both B-capsids (which contain no DNA) and C-capsids (which are fully packaged) were recorded and reconstructions were calculated from the first exposures, corresponding to a cumulative electron dose of 6-7 e-/A2, and from later exposures (25-40 e-/A2). Experimental procedures were standardized to ensure that perceived changes in the micrographs and reconstructions would be attributable to radiation damage alone. The effects of the higher doses in both the micrographs and the reconstructions were expressed as a progressive blurring of the finer details, corresponding to a delocalization of structure in the ice-embedded specimens. The resolutions of the reconstructions were quantified according to a form of the Fourier ring correlation coefficient criterion, according to which the first-exposure reconstructions had resolutions of 30-36 A. The fifth-exposure B-capsid reconstruction had comparable nominal resolution, although it exhibited progressively lower correlations at higher spatial frequencies. Qualitatively similar changes in the series of C-capsid reconstructions were observed although they were more pronounced, presumably because these micrographs had lower contrast and signal-to-noise ratios. We infer that the observed changes in the images and reconstructions and the concomitant loss in contrast in the immediate vicinity of the capsid surface may reflect radiation-induced perturbation of molecular structure and/or the release of peptide fragments. Nevertheless, the observed changes are relatively subtle, at least at the operational resolution of this study; overall, our results support earlier indications (M. F. Schmid et al. J. Struct. Biol. 108, 62-68, 1992) that prospects are quite good for tilt-series reconstructions from cryoelectron micrographs, including six to eight views of the same specimen.

Capsid↗
PubMed1991

Chrysotile asbestos and health in Zimbabwe: II. Health status survey of active miners and millers.

As part of the effort to establish industrial practice and public policy regarding asbestos in Zimbabwe, we have conducted a cross-sectional study of the chrysotile mines and mills. A stratified random sample of workers with greater than 10 years of exposure has been evaluated by spirometry, chest radiographs, and employment history. The latter was converted to quantitative estimates of exposure dose, using a matrix based on measured and reconstructed fiber levels for each job and facility during the years of work. Based on these data, a clear dose-response between asbestos exposure and functional loss has been demonstrated, with mean losses from predicted of about 400-600 cc in vital capacity in the 10% of the population with heaviest exposures. Low-grade parenchymal radiographic abnormalities (ILO grade greater than or equal to 1/0) were evident in 8.7% of the total study group and were almost 10 times more common in those with more than 100 fibers/cc.years cumulative exposure than in those with 16 fibers/cc.years or less. Pleural disease was relatively rare, occurring in just under 10% of the study group, and was unrelated to exposure dose. Overall, these findings are compatible with results of similar studies in Quebec and Swaziland and suggest that similar control strategies are probably indicated.

Asbestos↗
PubMed2006

2004 update of dosimetry for the Utah Thyroid Cohort Study.

In the 1980s, individual thyroid doses and uncertainties were estimated for members of a cohort of children identified in 1965 in Utah and Nevada who had potentially been exposed to fallout from the Nevada Test Site. That reconstruction represented the first comprehensive assessment of doses received by the cohort and was the first large effort to assess the uncertainty of dose on an individual person basis. The data on dose and thyroid disease prevalence during different periods were subsequently used in an analysis to determine risks of radiogenic thyroid disease. This cohort has received periodic medical follow-up to observe changes in disease frequency and to reassess the previously reported radiation-related risks, most recently after a Congressional mandate in 1998. In a recent effort to restore the databases and computer codes used to estimate doses in the 1980s, various deficiencies were found in the estimated doses due to improperly operating computer codes, corruption of secondary data files, and lack of quality control procedures. From 2001 through 2004, the dosimetry system was restored and corrected and all doses were recalculated. In addition, two parameter values were updated. While the mean of all doses has not changed significantly, many individual doses have changed by more than an order of magnitude.

Body Burden↗
PubMed1997

Successive alteration and recovery of epidermal differentiation and morphogenesis after specific UVB-damages in skin reconstructed in vitro.

The sequence of events affecting skin morphogenesis occurring after a single exposure to UVB was investigated on a model of human skin reconstructed in vitro. The biologically efficient dose (BED) able to induce the early UVB-DNA damages such as pyrimidine dimers, sunburn cells, and apoptotic keratinocytes was determined as 50 mJ/cm2. The subsequent changes induced during a period of 14 days following irradiation were analyzed. Up to Day 3, an epidermal disorganization led to a parakeratotic epidermis characterized by nucleated horny layers, as well as the down regulation of major markers of keratinocyte differentiation such as keratin 10, loricrin, filaggrin, and the keratinocyte transglutaminase (type I). On the contrary, the expression of involucrin and spr1 seemed to be unaffected, indicating distinct responses to UVB of proteins involved in keratinocyte differentiation. A progressive regeneration of normal epidermal morphogenesis begins from Day 4 leading to the normalization of keratinocyte differentiation at Day 10 to 14. In parallel, epidermal proliferation was increased. Taken together, these findings show that in skin reconstructed in vitro, UVB exposure leads to major epidermal developmental changes characterized by (i) an early apoptotic process, (ii) a subsequent down-regulation of specific keratinocyte differentiation markers, and (iii) the recovery of both the early and delayed effects resulting in normal epidermal morphogenesis.

Apoptosis↗
PubMed2005

[Three-dimensional reconstruction of human organs based on magnetic resonance imaging data].

OBJECTIVE: To build proper three-dimensional models of human organs for radiation dose calculation. METHOD: Human organ models were built by contour reconstruction algorithm conforming to 4 criteria. The contours of the organs were extracted based on the contours of the reconstructed organ surfaces, and the three-dimensional models with smooth surface, exact structure and good visibility were completed by computer graphic techniques such as lighting, smoothing, and normal average. RESULT AND CONCLUSION: Several organ models were successfully reconstructed, suggesting that this method is suitable for building three-dimensional digital human organ models which can meet the need for dose calculation.

Humans↗
PubMed1998

A new volumetric CT machine for dental imaging based on the cone-beam technique: preliminary results.

The objective of this paper is to present a new type of volumetric CT which uses the cone-beam technique instead of traditional fan-beam technique. The machine is dedicated to the dento-maxillo-facial imaging, particularly for planning in the field of implantology. The main characteristics of the unit are presented with reference to the technical parameters as well as the software performance. Images obtained are reported as various 2D sections of a volume reconstruction. Also, measurements of the geometric accuracy and the radiation dose absorbed by the patient are obtained using specific phantoms. Absorbed dose is compared with that given off by spiral CT. Geometric accuracy, evaluated with reference to various reconstruction modalities and different spatial orientations, is 0.8-1% for width measurements and 2.2% for height measurements. Radiation dose absorbed during the scan shows different profiles in central and peripheral axes. As regards the maximum value of the central profile, dose from the new unit is approximately one sixth that of traditional spiral CT. The new system appears to be very promising in dentomaxillo-facial imaging and, due to the good ratio between performance and low cost, together with low radiation dose, very interesting in view of large-scale use of the CT technique in such diagnostic applications.

Absorption↗
PubMed1993

Allograft degeneration in infant pulmonary valve allograft recipients.

Infants who have undergone pulmonary valve allograft reconstruction of their right ventricular outflow tract (RVOT), experience an increased incidence of allograft fibrocalcification and valvar insufficiency, compared to older children. Since 1985, 137 pediatric patients have received a cryopreserved pulmonary valve allograft to repair their RVOT. One hundred and five patients were 1 year of age or more and 32 were younger than 1 year at operation. In the former group, there were 11 hospital deaths (10%). Ninety-four operative survivors have been followed clinically for one month to 7.2 years (mean: 3.4 years). One patient required cardiac transplant secondary to myocardial dysfunction. There have been three late deaths (3%), and two children (2%) have undergone reoperation to replace the allograft. In the infant group, there were eight hospital deaths (25%). During 1 month to 6.8 years (mean: 2.2 years) of clinical follow up, there have been six late deaths (25%), and four children (22%) have required allograft explant. The most common indication for reoperation has been allograft fibrocalcification and valvar insufficiency. The relatively high incidence of early allograft failure in infants, which may have an immunologic etiology, has prompted consideration of nonviable allografts or low dose cyclosporine as alternatives when surgical reconstruction of the RVOT is required in children younger than 1 year of age.

Adolescent↗
PubMed1999

Study of ill-conditioning of Linac stereotactic irradiation subspaces using singular values decomposition analysis.

A Linac stereotactic irradiation space is characterized by different angular separations of beams because of the geometry of the stereotactic irradiation. The regions of the stereotactic space characterized by low angular separations are one of the causes of ill-conditioning of the stereotactic irradiation inverse problem. The singular value decomposition (SVD) is a powerful mathematical analysis that permits the measurement of the ill-conditioning of the stereotactic irradiation problem. This study examines the ill-conditioning of the stereotactic irradiation space, provoked by the different angular separations of beams, using the SVD analysis. We subdivided the maximum irradiation space (MIS: (AA)AP x (AA)RL = 180 degrees x 180 degrees) into irradiation subspaces (ISSs), each characterized by its own angular separation. We studied the influence of ISSs on the SVD analysis and the evolution of the reconstruction quality of well defined three-dimensional dose matrices in each configuration. The more the ISS is characterized by low angular separation the more the condition number and the reconstruction inaccuracy are increased. Based on the above results we created two reduced irradiation spaces (RIS: (AA)AP x (AA)RL = 180 degrees x 140 degrees and (AA)AP x (AA)RL = 180 degrees x 120 degrees) and compared the reconstruction quality of the RISs with respect to the MIS. The more an irradiation space is free of low angular separations the more the irradiation space contains useful singular components.

Humans↗
PubMed2006

EPR/alanine dosimetry in LDR brachytherapy--a feasibility study.

In this study, we present the results of in vivo dosimetry, using electron paramagnetic resonance in l-alanine, performed on 13 patients treated for gynaecological cancers. The doses from (137)Cs (12 samples) and (192)Ir (one sample) brachytherapy sources were determined inside vagina. The detectors had a form of small cellulose capsules tightly filled with crystalline alanine. The positions of the detectors were reconstructed from two orthogonal radiographs. The planned doses were calculated with a computer planning system (PLATO, Nucletron). The relative deviations between planned and measured doses ranged from -23 to +14%. The mean deviation from the prescribed dose was relatively low (-5%) with SD of 10%. The main sources of differences between the measured and calculated doses were attributed to uncertainty in the determination of the detector position inside the patient's body and to uncontrolled changes in the detector position during the treatment.

Alanine↗
PubMed2005

Cone-beam-CT guided radiation therapy: technical implementation.

BACKGROUND AND PURPOSE: X-ray volumetric imaging system (XVI) mounted on a linear accelerator is available for image guidance applications. In preparation for clinical implementation, phantom and patient imaging studies were conducted to determine the irradiation parameters that would trade-off image quality, patient dose and scanning time. PATIENTS AND METHODS: The XVI image quality and imaging dose were benchmarked against those obtained with a helical CT scanner for a head and body phantom. The irradiation parameters were varied including the total imaging dose, number of projections, field of view, reconstruction resolution and use of a scatter rejection grid. We characterized the image quality based on relative contrast, noise, contrast to noise ratio (CNR) and point spread function (PSF). XVI scans of pelvis, head and neck and lung patients were acquired and submitted to a range of observers to identify the favorable reconstruction parameters. RESULTS: Phantom studies have demonstrated that a scatter rejection grid reduces photon scattering and improves the image uniformity. For the body phantom, the helical CT and the wide field XVI technique produce similar image quality, with surface doses of 0.025 and 0.044 Gy respectively. We have demonstrated that the local tomography technique improves the image contrast and the CNR while reducing the skin dose by 40-50% compared to the wide field technique. Clinical scans of head and neck, lung and prostate patients present good soft tissue contrast and excellent bone definition. CONCLUSIONS: With adjustment of irradiation parameters and an imaging surface dose of less than 0.05 Gy, high quality XVI images can be obtained for a phantom simulating the body thickness. XVI is currently feasible for image-guided treatments of head and neck, torso and pelvic areas using soft tissue and bony structures.

Humans↗
PubMed2004

Endogenous ACTH concentration-dependent drive of pulsatile cortisol secretion in the human.

According to current regulatory concepts, pulsatile ACTH concentrations (CON) stimulate time-lagged cortisol secretion rates (SEC) via an implicit CON-SEC dose-response relationship. The present analyses reconstruct nonlinear properties of this in vivo agonist-response interface noninvasively in order to investigate pulse-by-pulse coupling consistency and to obviate the need to infuse isotopes or exogenous effectors, which may disrupt pathway interactions. This approach required an ensemble strategy of 1) measuring ACTH and cortisol CON in plasma sampled every 10 min for 24 h in 32 healthy adults, and 2) estimating simultaneously a) variable-waveform ACTH and cortisol SEC bursts superimposed upon fixed basal SEC; b) biexponential kinetics of ACTH and cortisol disappearance; c) nonequilibrium exchange of cortisol among free and cortisol-binding globulin (CBG)- and albumin-bound moieties; d) two SEC-burst shapes demarcated by a statistically defined day/night boundary; e) feedforward efficacy, potency, and sensitivity; and f) stochastic variability in feedforward measures over time. Thereby, we estimate 1) ACTH SEC (microg.l(-1).day(-1)) of 0.27 +/- 0.04 basal and 0.87 +/- 0.07 pulsatile (means +/- SE); 2) cortisol SEC (micromol.l(-1).day(-1)) of 0.10 +/- 0.01 basal and 3.5 +/- 0.20 pulsatile; 3) free cortisol half-lives (min) of 1.8 +/- 0.20 (diffusion/advection) and 4.1 +/- 0.30 (elimination) and a half-life of total cortisol of 49 +/- 2.4 and of ACTH of 20 +/- 1.3; 4) ACTH potency (EC(50), ng/l) of 26 +/- 2.4, efficacy (nmol.l(-1).min(-1)) 10 +/- 1.8, and sensitivity (slope units) 0.65 +/- 0.09; 5) night/day augmentation of ACTH and cortisol SEC-burst mass by 2.1- and 1.7-fold (median); 6) abbreviation of the modal time to maximal ACTH and cortisol SEC rates by 4.4- and 4.3-fold, respectively, after a change point clock time of 0205 (median); 7) in vivo percentage distribution of cortisol as 6% free, 14% albumin bound, and 80% CBG bound with an absolute free cortisol CON (nmol/l) 11.5 +/- 0.54; and 8) significant (mean CV) stochastic variability in feedforward efficacy (140%), potency (38%), and sensitivity (56%) within the succession of paired ACTH/cortisol pulses of any given subject. In conclusion, the present composite formulation illustrates a platform for dissecting mechanisms of in vivo regulation of effector-response properties noninvasively in the corticotropic axis of the uninfused individual.

Adrenal Cortex↗
PubMed1997

Automated electron microscope tomography of frozen-hydrated chromatin: the irregular three-dimensional zigzag architecture persists in compact, isolated fibers.

The potential of electron microscope tomography as a tool for obtaining three-dimensional (3D) information about large macromolecular assemblies is greatly extended by automation of data collection. With the implementation of automated control of tilting, focusing, and digital image recording described here, tilt series of frozen-hydrated specimens can be collected with the requisite low dose. Long chromatin fibers were prepared in 90 mM monovalent ions to maintain a fully compact conformation, and after vitrification were completely contained within the ice layer. Tilt series of this material were recorded at 5 degrees tilt increments between +60 degrees and -60 degrees, with a cumulative dose of approximately 35 e-/A2 for the series. This extremely low dose data was successfully aligned, then reconstructed by weighted backprojection. The underlying architecture of the fibers is an irregular 3D zigzag of interconnected nucleosomes, with the linker DNA between successive nucleosomes in a largely extended conformation. The visualization of this structural motif within long, frozen-hydrated chromatin fibers at relatively high salt extends our previous studies on small fragments at low ionic strength and is in agreement with the observation of this architecture in chromatin fibers in situ in sectioned nuclei.

Animals↗
PubMed1998

Contrast-enhanced magnetisation transfer MRI in metastatic lesions of the brain.

Our purpose was to compare prospectively the sensitivity of contrast-enhanced magnetisation transfer (MT) MRI and gradient-echo (GE) T1-weighted images in metastatic disease of the brain. We studied 52 patients with brain metastases, using conventional T1-weighted GE and MT spin-echo (SE) images after the same standard dose of gadolinium. Axial 5-mm reconstructions of GE data were compared with 5-mm MT images in the same plane. Metastases were counted independently by two neuroradiologists. In 12 patients (23%) MT imaging showed more metastases than GE images (P = 0.03). We detected 68 more metastases with the former technique.

Adult↗
PubMed1995

Complete myocardial revascularization through a right thoracotomy.

We report the case of a 57-year-old woman who benefited from a complete revascularization of the heart, including a circumflex marginal coronary bypass grafting, through a right thoracotomy. This approach avoids sternal wound complications that can occur after high-dose mediastinal radiotherapy and omental flap reconstruction on the sternum.

Adenocarcinoma↗
PubMed1984

Inexact three-dimensional reconstruction of a biological macromolecule from a restricted number of projections.

A computer-generated three-dimensional model of Lumbricus terrestris hemoglobin has been obtained by reconstruction from four STEM low-dose computer-averaged micrographs. X-ray projections of a wooden model constructed from the calculated two-dimensional sections through the molecule were generally consistent with the original STEM projections of the hemoglobin and suggest the presence of large gaps between the central regions of adjacent 1/12th subunits of opposite tiers.

Animals↗