Biomedical subjects

D A Low

Publications and source records attributed to D A Low.

At least 37 records · Page 2Linked to original sources

PubMed2000

A simple technique for alignment of perineal needle template to ultrasound image grid for permanent prostate implants.

Proper alignment of a needle template and ultrasound software grid is required to accurately deliver permanent prostate seed implants optimized using pretreatment volume studies. Correct alignment may also reduce tissue edema, morbidity, and the time and labor required to deliver permanent prostate seed implants. A technique has been developed to rapidly assess (and, if necessary, improve) the alignment using a custom-designed water phantom. Verification of needle positions can be conducted within 1 mm and requires less than ten minutes. We have instituted the technique as a part of our periodic quality assurance program.

Biophysical Phenomena↗

PubMed2000

Superficial doses from serial tomotherapy delivery.

Serial tomotherapy patients are treated using a commercial computer-controlled treatment planning and delivery system and a linear accelerator in arc mode. Target volumes are irradiated using sequential 1.68-cm-thick slices with the patient moved between each successive slice delivery. Due to the method of delivery, superficial doses from a course of intensity modulated radiation therapy may be significantly different from doses delivered with conventional radiation therapy. An experimental investigation was conducted to determine the superficial depth-dose distribution for geometric target volumes. Treatment plans were conducted for 5-cm-diam, 5-cm-long right cylindrical target volumes embedded in a 16-cm-diam, 12-cm-long water-equivalent cylindrical phantom. Three experiments were conducted with centrally located, off-centered, and superficial targets. Doses at superficial depths were measured using 3 x 3 x 1 mm3 thermoluminescent dosimetry chips. For all three targets, the measured doses were slightly greater than the calculated doses. Doses measured in the buildup region for the superficial target indicated that bolus would be required to provide the prescribed dose at the phantom surface.

Algorithms↗

PubMed2000

Evidence of commonality between canine and human extraintestinal pathogenic Escherichia coli strains that express papG allele III.

Although dogs have been proposed as carriers of extraintestinal pathogenic Escherichia coli (ExPEC) with infectious potential for humans, presumed host species-specific differences between canine and human ExPEC strains have cast doubt on this hypothesis. The recent discovery that allele III of papG (the P fimbrial adhesin gene) predominates among human cystitis isolates and confers an adherence phenotype resembling that of canine ExPEC prompted the present reevaluation of the canine-human ExPEC connection. Sixteen paired pap-positive urine and rectal E. coli isolates from dogs with urinary tract infection were studied. papG (adhesin) and papA (pilin) allele type, agglutination phenotypes, virulence factor genotypes, and randomly amplified polymorphic DNA and pulsed-field gel electrophoresis fingerprints were analyzed and compared with those of human ExPEC controls. The 16 canine strains contained predominantly papG allele III. Agglutination phenotypes segregated strictly according to papG allele status and were homogeneous among strains with the same papG allele profile irrespective of their human versus canine origin. Canine and human PapG variant III peptide sequences were highly homologous, without host species-specific differences. The most prevalent canine papA allele was F48, a novel variant recently identified among human urosepsis isolates. In addition to pap, human ExPEC-associated virulence genes detected among the canine strains included sfa/focDE, sfaS, fyuA, hlyA, cnf1, cdtB, kpsMT-II and -III, rfc, traT, ompT, and a marker for a pathogenicity-associated island from archetypal human ExPEC strain CFT073. Molecular fingerprinting confirmed the fecal origin of all but one canine urine isolate and showed one pair of O6 canine urine and fecal isolates to be extremely similar to an O6 human urosepsis isolate with which they shared all other genotypic and phenotypic characteristics analyzed. These data demonstrate that canine ExPEC strains are similar to, and in some instances essentially indistinguishable from, human ExPEC strains, which implicates dogs and their feces as potential reservoirs of E. coli with infectious potential for humans.

Adhesins, Escherichia coli↗

PubMed2000

Assessment of bacterial pathogenesis by analysis of gene expression in the host.

A number of techniques have been developed to assess the expression of microbial virulence genes within the host (in vivo). These studies have shown that bacteria employ a wide variety of mechanisms to coordinately regulate the expression of these genes during infection. Two tenets have emerged from these studies: bacterial adaptation responses are critical to growth within the host, and interactions between microorganisms and the microenvironments of their hosts cannot be revealed from in vitro studies alone. Results that support these tenets include (i) the prevalent class of in vivo expressed genes are involved in adaptation to environmental stresses, (ii) pathogens recovered from host tissues (versus laboratory growth) are often more resistant to host killing mechanisms, and (iii) virulence gene expression can differ in the animal compared to laboratory media. Thus, pathogenicity comprises the unique ability to adapt to the varied host milieus encountered as the infection proceeds.

Bacteria↗

PubMed1999

Abutment region dosimetry for serial tomotherapy.

PURPOSE: A commercial intensity modulated radiation therapy system (Corvus, NOMOS Corp.) is presently used in our clinic to generate optimized dose distributions delivered using a proprietary dynamic multileaf collimator (DMLC) (MIMiC) composed of 20 opposed leaf pairs. On our accelerator (Clinac 600C/D, Varian Associates, Inc.) each MIMiC leaf projects to either 1.00 x 0.84 or 1.00 x 1.70 cm2 (depending on the treatment plan and termed 1 cm or 2 cm mode, respectively). The MIMiC is used to deliver serial (axial) tomotherapy treatment plans, in which the beam is delivered to a nearly cylindrical volume as the DMLC is rotated about the patient. For longer targets, the patient is moved (indexed) between treatments a distance corresponding to the projected leaf width. The treatment relies on precise indexing and a method was developed to measure the precision of indexing devices. A treatment planning study of the dosimetric effects of incorrect patient indexing and concluded that a dose heterogeneity of 10% mm(-1) resulted. Because the results may be sensitive to the dose model accuracy, we conducted a measurement-based investigation of the consequences of incorrect indexing using our accelerator. Although the indexing provides an accurate field abutment along the isocenter, due to beam divergence, hot and cold spots will be produced below and above isocenter, respectively, when less than 300 degree arcs were used. A preliminary study recently determined that for a 290 degree rotation in 1 cm mode, 15% cold and 7% hot spots were delivered to 7 cm above and below isocenter, respectively. This study completes the earlier work by investigating the dose heterogeneity as a function of position relative to the axis of rotation, arc length, and leaf width. The influence of random daily patient positioning errors is also investigated. METHODS AND MATERIALS: Treatment plans were generated using 8.0 cm diameter cylindrical target volumes within a homogeneous rectilinear film phantom. The plans included both 1 and 2 cm mode, optimized for 300 degrees, 240 degrees, and 180 degrees gantry rotations. Coronal-oriented films were irradiated throughout the target volumes and scanned using a laser film digitizer. The central target irradiated in 1 cm mode was also used to investigate the effects of incorrect couch indexing. RESULTS: The dose error as a function of couch index error was 25% mm(-1), significantly greater than previously reported. The clinically provided indexing system yielded 0.10 mm indexing precision. The intrinsic dose distributions indicated that more heterogeneous dose distributions resulted from the use of smaller gantry angle ranges and larger leaf projections. Using 300 degrees gantry angle and 1 cm mode yielded 7% hot and 15% cold spots 7 cm below and above isocenter, respectively. When a 180 degree gantry angle was used, the values changed to 22% hot and 27% cold spots for the same locations. The heterogeneities for the 2 cm mode were 70% greater than the corresponding 1 cm values. CONCLUSIONS: While serial tomotherapy is used to deliver highly conformal dose distributions, significant dosimetric factors must be considered before treatment. The patient must be immobilized during treatment to avoid dose heterogeneities caused by incorrect indexing due to patient movement. Even under ideal conditions, beam divergence can cause significant abutment-region dose heterogeneities. The use of larger gantry angle ranges, smaller leaf widths, and appropriate locations of the gantry rotation axis can minimize these effects.

Equipment Design↗

PubMed1999

An essential role for DNA adenine methylation in bacterial virulence.

Salmonella typhimurium lacking DNA adenine methylase (Dam) were fully proficient in colonization of mucosal sites but showed severe defects in colonization of deeper tissue sites. These Dam- mutants were totally avirulent and were effective as live vaccines against murine typhoid fever. Dam regulated the expression of at least 20 genes known to be induced during infection; a subset of these genes are among those activated by the PhoP global virulence regulator. PhoP, in turn, affected Dam methylation at specific genomic sites, as evidenced by alterations in DNA methylation patterns. Dam inhibitors are likely to have broad antimicrobial action, and Dam- derivatives of these pathogens may serve as live attenuated vaccines.

Adenine↗

PubMed1999

Evaluation of polymer gels and MRI as a 3-D dosimeter for intensity-modulated radiation therapy.

BANG gel (MGS Research, Inc., Guilford, CT) has been evaluated for measuring intensity-modulated radiation therapy (IMRT) dose distributions. Treatment plans with target doses of 1500 cGy were generated by the Peacock IMRT system (NOMOS Corp., Sewickley, PA) using test target volumes. The gels were enclosed in 13 cm outer diameter cylindrical glass vessels. Dose calibration was conducted using seven smaller (4 cm diameter) cylindrical glass vessels irradiated to 0-1800 cGy in 300 cGy increments. Three-dimensional maps of the proton relaxation rate R2 were obtained using a 1.5 T magnetic resonance imaging (MRI) system (Siemens Medical Systems, Erlangen, Germany) and correlated with dose. A Hahn spin echo sequence was used with TR = 3 s, TE = 20 and 100 ms, NEX = 1, using 1 x 1 x 3 mm3 voxels. The MRI measurements were repeated weekly to identify the gel-aging characteristics. Ionization chamber, thermoluminescent dosimetry (TLD), and film dosimetry measurements of the IMRT dose distributions were obtained to compare against the gel results. The other dosimeters were used in a phantom with the same external cross-section as the gel phantom. The irradiated R2 values of the large vessels did not precisely track the smaller vessels, so the ionization chamber measurements were used to normalize the gel dose distributions. The point-to-point standard deviation of the gel dose measurements was 7.0 cGy. When compared with the ionization chamber measurements averaged over the chamber volume, 1% agreement was obtained. Comparisons against radiographic film dose distribution measurements and the treatment planning dose distribution calculation were used to determine the spatial localization accuracy of the gel and MRI. Spatial localization was better than 2 mm, and the dose was accurately determined by the gel both within and outside the target. The TLD chips were placed throughout the phantom to determine gel measurement precision in high- and low-dose regions. A multidimensional dose comparison tool that simultaneously examines the dose-difference and distance-to-agreement was used to evaluate the gel in both low-and high-dose gradient regions. When 3% and 3 mm criteria were used for the comparisons, more than 90% of the TLD measurements agreed with the gel, with the worst of 309 TLD chip measurements disagreeing by 40% of the criteria. All four MRI measurement session gel-measured dose distributions were compared to evaluate the time behavior of the gel. The low-dose regions were evaluated by comparison with TLD measurements at selected points, while high-dose regions were evaluated by directly comparing measured dose distributions. Tests using the multidimensional comparison tool showed detectable degradation beyond one week postirradiation, but all low-dose measurements passed relative to the test criteria and the dose distributions showed few regions that failed.

Biophysical Phenomena↗

PubMed1999

Quantitative optical densitometry with scanning-laser film digitizers.

A new process for eliminating two types of artifacts inherent in commercially available transmission scanning-laser film digitizers is presented. The first kind of artifact results in nonreproducible interference-pattern fluctuations as large as 7%. The second kind results in spreading of transmitted light from low-to-high optical density (OD) in regions with rapidly varying ODs, producing errors as large as 50%. These OD artifacts cause the loss of precision for films with low-OD regions (first type) and the loss of accuracy for films with regions of high-OD near high-OD gradients (second type). Test radiochromic films, produced by uniform exposure to a 6 MV photon beam and a high dose rate 192Ir brachytherapy source, along with test radiographic films were used to characterize the artifacts of a commercially available scanning-laser film digitizer. The interference-pattern artifact was eliminated by digitizing the films on a masked diffusing ground-glass scanning bed. The light-transmission artifact was eliminated through discrete-fast-Fourier-transform (DFFT) deconvolution of transmission profiles with measured digitizer line-spread functions. Obtaining precise OD distributions after the DFFT deconvolution required prior removal of the interference-pattern artifact and application of a low-pass Wiener noise filter. Light-transmission artifacts are particularly significant for applications requiring measurement of high-gradient OD distributions, such as brachytherapy or conformal photon-beam film dosimetry and quantitation of two-dimensional electrophoresis gels. Errors as large as 15%-35% occur in OD distributions representative of these applications. The data collection and correction process developed in this study successfully removes these artifacts.

Biophysical Phenomena↗

PubMed1998

Quality assurance of serial tomotherapy for head and neck patient treatments.

PURPOSE: A commercial serial tomotherapy intensity-modulated radiation therapy (IMRT) treatment planning (Peacock, NOMOS Corp., Sewickley, PA) and delivery system is in clinical use. The dose distributions are highly conformal, with large dose gradients often surrounding critical structures, and require accurate localization and dose delivery. Accelerator and patient-specific quality assurance (QA) procedures have been developed that address the localization, normalization, and delivery of the IMRT dose distributions. METHODS AND MATERIALS: The dose distribution delivered by serial tomotherapy is highly sensitive to the accuracy of the longitudinal couch motion. There is also an unknown sensitivity of the dose distribution on the dynamic mutlileaf collimator alignment. QA procedures were implemented that assess these geometric parameters. Evaluations of patient positioning accuracy and stability were conducted by exposing portal films before (single exposure) and after (single or double exposure) treatments. The films were acquired with sequential exposures using the largest available fixed multileaf portal (3.36 x 20 cm2). Comparison was made against digitally reconstructed radiographs generated using independent software and appropriate beam geometries. The delivered dose was verified using homogeneous cubic phantoms. Radiographic film was used to determine the localization accuracy of the delivered isodose distributions, and ionization chambers and thermoluminescent dosimetry (TLD) chips were used to verify absolute dose at selected points. Ionization chamber measurements were confined to the target dose regions and TLD measurements were obtained throughout the irradiated volumes. Because many more TLD measurements were made, a statistical evaluation of the measured-to-calculated dose ratio was possible. RESULTS: The accelerator QA techniques provided adequate monitoring of the geometric patient movement and dynamic multileaf collimator alignment and positional stability. The absolute delivered dose as measured with the ionization chamber varied from 0.94 to 0.98. Based on these measurements, the delivered monitor units for both subsequent QA measurements and patient treatments were adjusted by the ratio of measured to calculated dose. TLD measurements showed agreement, on average, with the ionization chamber measurements. The distribution of TLD measurements in the high-dose regions indicated that measured doses agreed within 4.2% standard deviation of the calculated doses. In the low-dose regions, the measured doses were on average 5% greater than the calculated doses, due to a lack of leakage dose in the dose calculation algorithm. CONCLUSIONS: The QA system provided adequate determination of the geometric and dosimetric quantities involved in the use of IMRT for the head and neck. Ionization chamber and TLD measurements provided accurate determination of the absolute delivered dose throughout target volumes and critical structures, and radiographic film yielded precise dose distribution localization verification. Portal film acquisition and subsequent portal film analysis using 3.36 x 20 cm2 portals proved useful in the evaluation of patient immobilization quality. Adequate bony landmarks were imaged when carefully selected portals were used.

Algorithms↗

PubMed1998

A critical evaluation of the planning target volume for 3-D conformal radiotherapy of prostate cancer.

PURPOSE: To determine an adequate planning target volume (PTV) margin for three-dimensional conformal radiotherapy (3D CRT) of prostate cancer, the uncertainties in the internal positions of the prostate and seminal vesicles (SV) and in the treatment setups were measured. METHODS AND MATERIALS: Weekly computed tomography (CT) scans of the pelvis (n=51) and daily electronic portal images (n=1630) were reviewed for eight patients who received seven-field 3D CRT for prostate cancer. The CT scans were registered in three dimensions to the original planning CT scan using commercially available software to measure the center-of volume (COV) motion of the prostate and SV. The daily portal images were registered to the corresponding simulation films to measure the setup displacements. The standard deviation (SD) of the internal organ motions was added to the SD of the setups in quadrature to determine the total uncertainty. Positive directions were left, anterior, and superior. Rotations necessary to register the CT scans and portal images were minimal and not further analyzed. RESULTS: The mean motion for the COV of the prostate+/-the SD was 0+/-0.9 mm in the left-right (LR), 0.5+/-2.6 mm in the anterior-posterior (AP), and 1.5+/-3.9 mm in the superior-inferior (SI) directions. The mean motion for the COV of the SV+/-the SD was 0.3+/-1.7 mm in the LR, 0.7+/-3.8 mm in the AP, and 0.9+/-3.5 mm in the SI directions. For all patients the mean isocenter displacement+/-the SD was 0+/-3.1 mm in the LR, 1.4+/-3.0 mm in the AP, and -0.4+/-2.1 mm in the SI directions. The total uncertainty for the prostate was 3.2 mm, 4.0 mm, and 4.4 mm in the LR, AP, and SI directions, respectively. For the SV, the total uncertainty was 3.5, 4.8, and 4.1 mm in the LR, AP, and SI directions, respectively. CONCLUSIONS: PTV margins of 10 to 16 mm are required to encompass all (99%) possible positions of the prostate or SV during 3D CRT. PTV margins of 7 to 11 mm will encompass the measured uncertainties with a 95% probability. PTV margins of 5 mm may not adequately cover the intended volume.

Humans↗

PubMed1998

Whole-body dose from tomotherapy delivery.

PURPOSE: To measure whole-body dose in tomotherapy of the head and neck region resulting from internal patient scatter and linear accelerator leakage. METHODS AND MATERIALS: Treatments are performed using a commercial computer-controlled intensity modulated radiation therapy planning and delivery system (Peacock, NOMOS Corp.) and a 6-MV linear accelerator (Clinac 6/100, Varian Corp.). The patient dose outside the treatment field is measured in a water-equivalent phantom using thermoluminescent dosimetry. The whole-body dose components from internal scatter and leakage are separately determined. The use of fixed-portal leakage and scattered radiation measurements to estimate the whole-body dose from tomotherapy is evaluated. RESULTS: The internally scattered dose is significant near the target, but becomes negligible relative to the leakage dose beyond 15 cm from the target. Dose at 10 cm from the target volume, due to internal scatter and leakage, is approximately 2.5% of the total target dose, reducing to 0.5% at 30 cm. The measured dose is relatively uniform throughout the phantom. CONCLUSION: The whole-body dose equivalent from a tomotherapy treatment is greater than that from conventional radiation therapy. Further studies are required to assess the trade-off between improved dose distribution conformality and a possible slight increase in radiation-induced fatal malignancies. The accuracy of using fixed-portal leakage and scattered dose measurements to estimate the whole-body dose from tomotherapy treatments is adequate, if the appropriate fixed-portal field size equivalent is used.

Head↗

PubMed1998

A commercial IMRT treatment-planning dose-calculation algorithm.

PURPOSE: The dose-calculation algorithm for a commercial arc-based intensity modulated radiation therapy (IMRT) treatment-planning and delivery system (Peacock, NOMOS Corporation) is described. METHODS AND MATERIALS: The IMRT delivery system uses a dynamically controlled multileaf collimator with 40 leaves that project on our accelerator to either 1.0 x 0.84 cm2 or 1.0 x 1.68 cm2 at isocenter arranged in two banks of 20 leaves each. The dose-calculation algorithm uses tissue-phantom ratios derived from percent depth dose measurements, measured relative output data, and single leaf profiles. Some compromises are made in the algorithm terms to enable more straightforward dosimetry measurements and to reduce dose computation times. The dose calculation algorithm is presented, and consequences of the approximations are investigated using previously published 4 MV photon beam data. RESULTS: Most of the approximations lead to dose errors of a few percent. However, the use of depth-invariant single-leaf profiles results in errors as large as 9% for 4 MV fixed beams. CONCLUSIONS: Large dosimetric errors are possible for small fixed fields using this algorithm. However, the algorithm is designed for tomotherapy dose delivery, where doses are delivered from multiple directions and depths. Investigations of the algorithm in more clinically relevant conditions have been conducted and show that the algorithm accuracy is 1.3% and therefore is clinically acceptable for tomotherapy.

Algorithms↗

PubMed1998

Phantoms for IMRT dose distribution measurement and treatment verification.

BACKGROUND: The verification of intensity-modulated radiation therapy (IMRT) patient treatment dose distributions is currently based on custom-built or modified dose measurement phantoms. The only commercially available IMRT treatment planning and delivery system (Peacock, NOMOS Corp.) is supplied with a film phantom that allows accurate spatial localization of the dose distribution using radiographic film. However, measurements using other dosimeters are necessary for the thorough verification of IMRT. METHODS: We have developed a phantom to enable dose measurements using a cylindrical ionization chamber and the localization of prescription isodose curves using a matrix of thermoluminescent dosimetry (TLD) chips. The external phantom cross-section is identical to that of the commercial phantom, to allow direct comparisons of measurements. A supplementary phantom has been fabricated to verify the IMRT dose distributions for pelvis treatments. RESULTS: To date, this phantom has been used for the verification of IMRT dose distributions for head and neck and prostate cancer treatments. Designs are also presented for a phantom insert to be used with polymerizing gels (e.g., BANG-2) to obtain volumetric dose distribution measurements. CONCLUSION: The phantoms have proven useful in the quantitative evaluation of IMRT treatments.

Head and Neck Neoplasms↗

PubMed1998

Regulation of uropathogenic Escherichia coli adhesin expression by DNA methylation.

Pap pili play an important role in the pathogenesis of upper urinary tract infections by enabling uropathogenic Escherichia coli to adhere to host epithelial cells. Pap pili are coded for by the pyelonephritis-associated pili (pap) operon, which consists of 11 genes required for the expression and assembly of Pap pili. Expression of Pap pili is regulated by a phase variation mechanism in which the pili expression state of the bacterial population is skewed between phase-on (expression positive) and phase-off (expression negative) states. Pap phase variation is controlled by the cooperative binding of leucine-responsive regulatory protein (Lrp) to two sets of Lrp binding sites in the upstream regulatory region of the pap operon. A single GATC sequence, which is the target site for deoxyadenosine methylase (Dam), is centrally located within each Lrp binding region. Dam plays a critical role in the expression of Pap pili via the formation of DNA methylation patterns. Methylation of GATC-I reduced the affinity of Lrp for pap DNA by about twofold. Conversely, Lrp specifically blocked methylation of pap GATC-I in vitro. These data support the hypothesis that Lrp and Dam compete for binding to GATC-I, and are consistent with previous results indicating that methylation of GATC-I is important for stability of the phase-off state.

Adhesins, Escherichia coli↗

PubMed1998

Geometric and dosimetric analysis of multileaf collimation conformity.

BACKGROUND AND PURPOSE: There is concern over the stepped edges of multileaf collimator (MLC) fields for target coverage compared with those of cerrobend. Despite recent reports dispelling this concern, users are still cautious when using MLCs for small fields. Leaf orientation can be a problem if one is required to orient the leaves along an axis not ideal for conformity (such as dynamic or universal wedge cases). In this study we examined the dependence of MLC field conformity on field size and elongation. MATERIALS AND METHODS: We examined circles of varying diameter and ellipses of varying eccentricity with leaves oriented along the major and minor axes of ellipses. The tests were both geometric, comparing areas of overblocking or underblocking (leaves inside and outside the field), and dosimetric, using radiographic films at depth in the beam's eye view plane. RESULTS: For the geometric comparison there is a rapid increase in non-conformity, defined as the percentage of overblocking or underblocking area, as the circle diameter decreases. For ellipses, when the leaves move along one axis direction, the conformity does not depend on the diameter of the same axis, but instead improves as the dimension of the axis in the non-leaf motion direction increases. The best conformity is achieved when the maximum number of leaves is used to shape the field. When the dosimetry is analyzed, the predictability of these trends decreases due to the impact of undulations (scatter), leaf inaccuracies and dosimetric uncertainties. CONCLUSIONS: We recommend that for small round fields MLC should be used with caution and that for ellipses the direction of leaf movement should be aligned with the minor axis whenever possible. Though these experiments are for idealized geometries, the observations can be applied to clinical fields. An MLC with a thinner leaf width could be beneficial for small round fields.

Humans↗

PubMed1998

Quantitative dosimetric verification of an IMRT planning and delivery system.

BACKGROUND AND PURPOSE: The accuracy of dose calculation and delivery of a commercial serial tomotherapy treatment planning and delivery system (Peacock. NOMOS Corporation) was experimentally determined. MATERIALS AND METHODS: External beam fluence distributions were optimized and delivered to test treatment plan target volumes, including three with cylindrical targets with diameters ranging from 2.0 to 6.2 cm and lengths of 0.9 through 4.8 cm, one using three cylindrical targets and two using C-shaped targets surrounding a critical structure, each with different dose distribution optimization criteria. Computer overlays of film-measured and calculated planar dose distributions were used to assess the dose calculation and delivery spatial accuracy. A 0.125 cm3 ionization chamber was used to conduct absolute point dosimetry verification. Thermoluminescent dosimetry chips, a small-volume ionization chamber and radiochromic film were used as independent checks of the ion chamber measurements. RESULTS: Spatial localization accuracy was found to be better than +/-2.0 mm in the transverse axes (with one exception of 3.0 mm) and +/-1.5 mm in the longitudinal axis. Dosimetric verification using single slice delivery versions of the plans showed that the relative dose distribution was accurate to +/-2% within and outside the target volumes (in high dose and low dose gradient regions) with a mean and standard deviation for all points of -0.05% and 1.1%, respectively. The absolute dose per monitor unit was found to vary by +/-3.5% of the mean value due to the lack of consideration for leakage radiation and the limited scattered radiation integration in the dose calculation algorithm. To deliver the prescribed dose, adjustment of the monitor units by the measured ratio would be required. CONCLUSIONS: The treatment planning and delivery system offered suitably accurate spatial registration and dose delivery of serial tomotherapy generated dose distributions. The quantitative dose comparisons were made as far as possible from abutment regions and examination of the dosimetry of these regions will also be important. Because of the variability in the dose per monitor unit and the complex nature of the calculation and delivery of serial tomotherapy, patient-specific quality assurance procedures will include a measurement of the delivered target dose.

Algorithms↗

PubMed1998

Thermoregulation of Escherichia coli pap transcription: H-NS is a temperature-dependent DNA methylation blocking factor.

The expression of Pap pili that facilitate the attachment of Escherichia coli to uroepithelial cells is shut off outside the host at temperatures below 26 degrees C. Ribonuclease protection analysis showed that this thermoregulatory response was rapid as evidenced by the absence of papBA transcripts, coding for Pap pilin, after only one generation of growth at 23 degrees C. The histone-like nucleoid structuring protein H-NS and DNA sequences within papB were required for thermoregulation, but the PapB and PapI regulatory proteins were not. In vivo analysis of pap DNA methylation patterns indicated that H-NS or a factor regulated by H-NS bound within the pap regulatory region at 23 degrees C but not at 37 degrees C, as evidenced by H-NS-dependent inhibition of methylation of the pap GATC sites designated GATC-I and GATC-II. These GATC sites lie upstream of the papBAp promoter and have been shown previously to play a role in controlling Pap pili expression by regulating the binding of Lrp, a global regulator that is essential for activating papBAp transcription. Competitive electrophoretic mobility shift analysis showed that H-NS bound specifically to a pap DNA fragment containing the GATC-I and GATC-II sites. Moreover, H-NS blocked methylation of these pap GATC sites in vitro: H-NS blocked pap GATC methylation at 1.4 microM but was unable to do so at higher concentrations at which non-specific binding occurred. Thus, non-specific binding of H-NS to pap DNA was not sufficient to inhibit methylation of the pap GATC sites. These results suggest that the ability of H-NS to act as a methylation blocking factor is dependent upon the formation of a specific complex of H-NS with pap regulatory DNA. We hypothesize that a function of H-NS such as oligomerization was altered at 23 degrees C, which enabled H-NS to repress pap gene expression through the formation of a specific nucleoprotein complex.

Artificial Gene Fusion↗

PubMed1998

A technique for the quantitative evaluation of dose distributions.

The commissioning of a three-dimensional treatment planning system requires comparisons of measured and calculated dose distributions. Techniques have been developed to facilitate quantitative comparisons, including superimposed isodoses, dose-difference, and distance-to-agreement (DTA) distributions. The criterion for acceptable calculation performance is generally defined as a tolerance of the dose and DTA in regions of low and high dose gradients, respectively. The dose difference and DTA distributions complement each other in their useful regions. A composite distribution has recently been developed that presents the dose difference in regions that fail both dose-difference and DTA comparison criteria. Although the composite distribution identifies locations where the calculation fails the preselected criteria, no numerical quality measure is provided for display or analysis. A technique is developed to unify dose distribution comparisons using the acceptance criteria. The measure of acceptability is the multidimensional distance between the measurement and calculation points in both the dose and the physical distance, scaled as a fraction of the acceptance criteria. In a space composed of dose and spatial coordinates, the acceptance criteria form an ellipsoid surface, the major axis scales of which are determined by individual acceptance criteria and the center of which is located at the measurement point in question. When the calculated dose distribution surface passes through the ellipsoid, the calculation passes the acceptance test for the measurement point. The minimum radial distance between the measurement point and the calculation points (expressed as a surface in the dose-distance space) is termed the gamma index. Regions where gamma > 1 correspond to locations where the calculation does not meet the acceptance criteria. The determination of gamma throughout the measured dose distribution provides a presentation that quantitatively indicates the calculation accuracy. Examples of a 6 MV beam penumbra are used to illustrate the gamma index.

Gamma Rays↗