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Biomedical subjects

S Webb

Publications and source records attributed to S Webb.

At least 91 records · Page 5Linked to original sources
PubMed1998

Development of the murine pulmonary vein and its relationship to the embryonic venous sinus.

BACKGROUND: Arguments concerning the development of the pulmonary vein, and its relationship to the embryonic venous sinus (sinus venosus) have continued for well over a century. Recently, attention has again been focused on the origin of the pulmonary vein. It has been suggested that, whereas the pulmonary vein originates from the left atrium in humans, in all other vertebrates it originates from the venous sinus, with subsequent transfer to the left atrium. The nature of this transfer has not, however, been elucidated, although there is speculation that the pulmonary vein is "pinched off" from the left side of the embryonic venous sinus. METHODS: We studied closely staged hearts of normal mouse embryos from a C57BL/6 x CBAcross days 10 and 11 of gestation (plug day = day 1). Two series of embryos were collected and fixed in 2% glutaraldehyde, 1% formaldehyde, buffered with 0.05 M sodium cacodylate pH 7.4 (adjusted to 330 mOsm with NaCl). One series was wax embedded, serially sectioned, and stained with Masson's trichrome. The second series was subject to microdissection and scanning electron microscopy. RESULTS: The atrial component of the heart tube is attached to the body of the embryo by reflections of the atrial myocardial wall. The attachment can be considered, from the outset, as the heart stalk, with the myocardial-mesodermal connections forming a horseshoe of tissue that projects ventrally into the lumen of the atrium, surrounding a single evagination in the midline of the embryo. This heart stalk is cranial to the connections of the tributaries of the embryonic venous sinus and ventral to the foregut. When traced through its developmental stages, the evagination in the centre of the stalk, which we describe as the pulmonary pit, is seen to become the portal of entry for the developing pulmonary vein. CONCLUSIONS: The heart stalk, representing the area used by the pulmonary vein to gain access to the heart, and analogous to the dorsal mesocardium, is, from the outset, discrete from the area occupied by the orifices of the horns of the embryonic venous sinus. The pulmonary vein does not, in the mouse, develop from the tissues that form the walls of the tributaries of the systemic venous sinus. Comparisons with other studies suggest that early events in the development of the pulmonary vein are likely to be the same in all mammals, including humans.

Animals↗
PubMed1998

The mouse with trisomy 16 as a model of human hearts with common atrioventricular junction.

OBJECTIVE: To establish if the mouse with trisomy 16 is a suitable animal model with which to elucidate the development of a common atrioventricular junction. METHODS: The junctional morphologies in the normal human heart and those with a common atrioventricular junction are compared and contrasted. These are then related to observations made in normal mice and those with trisomy 16. So as better to understand development, a full description is given first of the normal atrioventricular junctions. Developmental implications are discussed because failure of fusion of the endocardial cushions cannot account for all the anomalies found in RXR alpha knockout, and in iv/iv mice. RESULTS: Mice with trisomy 16 showed evidence of deficiencies of atrioventricular septation and possessed a common atrioventricular junction, but the valvar orifices were not balanced between the ventricles as is the case in humans. Whilst some mice showed affinities with human tricuspid atresia, other cardiac malformations in the mice had no counterparts in human cardiac pathology. In humans both "partial" and "complete" forms of "atrioventricular canal malformations" share a basically common muscular junctional morphology, the differences being due exclusively to the way the bridging leaflets are fused to each other and/or the septum. CONCLUSIONS: It is simplistic to use the mouse with trisomy 16 as a model for cardiac abnormalities seen in humans. A spectrum more comparable to humans is found in RXR knockout mice. Study of the iv/iv mouse may help elucidate the genetic steps involved in normal and abnormal atrioventricular septation.

Animals↗
PubMed1998

A cone-beam megavoltage CT scanner for treatment verification in conformal radiotherapy.

PURPOSE: A prototype scanner for large-volume megavoltage computed tomography (MVCT) in a clinical set-up is described. The ultimate aim is to improve treatment accuracy in conformal radiotherapy through patient set-up error reduction and transit dosimetry. MATERIALS AND METHODS: The scanner consists of a custom-built 2D CsI(Tl) crystal array viewed by a lens and a CCD camera. Image acquisition is synchronized with radiation pulses. The 2D projections resulting from a single continuous 360 degrees gantry rotation are reconstructed using a cone-beam tomography algorithm. Prior to reconstruction, the raw projections are calibrated and corrected for centre of rotation movement and accelerator output fluctuation. The performance of the system has been evaluated by reconstructing projections of open fields, test objects and a humanoid phantom. RESULTS: Hundreds of 2D projections can be acquired with a clinically-acceptable data collection time (about 2 min) and dose (approximately 40 cGy, with a possible four-fold reduction). A maximum density resolution of about 2% is achieved offering some soft tissue discrimination without using image enhancement tools. A spatial resolution of 2.5 mm is obtained. The reconstructed image intensity is linear with electron density over the range of interest. Coronal or sagittal slices through the 3D reconstruction of the humanoid phantom show a better delineation of structures than the corresponding portal images taken at the same orientation. CONCLUSIONS: A similar image quality to our current single-slice MVCT scanner is achieved with the advantage of providing tens of tomographic slices for a single gantry rotation. This work demonstrates the feasibility of clinical cone-beam MVCT and indicates how this prototype can be improved.

Image Processing, Computer-Assisted↗
PubMed1998

Defective lateralisation in children with congenitally malformed hearts.

Defects in lateralization can be studied from the stance of populations, the individual, or the systems of organs within each individual. Unfortunately, and confusingly, the same terms are being applied to each of these situations, but inevitably with different meanings. Thus, there is presently no consensus on how we should use terms such as "heterotaxy" and "situs ambiguus". By far the least ambiguous use of these words is encountered when they are applied to the organs. In fact, each system of organs can accurately and simply be described in terms of its left-right morphology. All those organs which are paired then can be described, when interpreted on the basis of their intrinsic morphology, as being usually arranged, mirror-imaged, or as showing left or right isomerism. Within the heart, these changes are seen only in the atrial segment. The criterion for distinction of rightness or leftness within the atrial segment is the extent of the pectinate muscles relative to the atrioventricular junction. Application of this criterion permits unequivocal recognition of symmetry as opposed to lateralization. The same holds good for the other organs. Within any individual organ, therefore, the situation is neither ambiguous nor heterotaxic. Instead, it is lateralised or symmetrical. Within the individual, in contrast, there may well be discrepancies in the expected disposition of the systems of organs which produces potential ambiguity. To dispel this ambiguity, it is necessary to provide a full catalogue. For example, persons with otherwise normally arranged organs may have left bronchial isomerism. Other persons may have discordance between the thoracic organs, which are usually arranged, and the abdominal organs, which are mirror-imaged, but no evidence of isomerism. Within the population, however, we are unaware of any genetically or environmentally induced syndrome in which all individuals show evidence of mirror-imagery, or of isomerism, or of specific discordance between the systems. In fact, all known syndromes encompass all types of defective lateralization. When attempting to identify the genetic mechanisms for production of the syndromes, therefore, it could be positively misleading to attempt to separate isomerism from other perceived forms of"heterotaxy". Our preference is to consider any deviation from the usual arrangement as heterotaxy, and to specify the specific arrangement of the organs within each malformed individual.

Child↗
PubMed1998

Improving calibration accuracy in gel dosimetry.

A new method of calibrating gel dosimeters (applicable to both Fricke and polyacrylamide gels) is presented which has intrinsically higher accuracy than current methods, and requires less gel. Two test-tubes of gel (inner diameter 2.5 cm, length 20 cm) are irradiated separately with a 10 x 10 cm2 field end-on in a water bath, such that the characteristic depth-dose curve is recorded in the gel. The calibration is then determined by fitting the depth-dose measured in water, against the measured change in relaxivity with depth in the gel. Increased accuracy is achieved in this simple depth-dose geometry by averaging the relaxivity at each depth. A large number of calibration data points, each with relatively high accuracy, are obtained. Calibration data over the full range of dose (1.6-10 Gy) is obtained by irradiating one test-tube to 10 Gy at dose maximum (Dmax), and the other to 4.5 Gy at Dmax. The new calibration method is compared with a 'standard method' where five identical test-tubes of gel were irradiated to different known doses between 2 and 10 Gy. The percentage uncertainties in the slope and intercept of the calibration fit are found to be lower with the new method by a factor of about 4 and 10 respectively, when compared with the standard method and with published values. The gel was found to respond linearly within the error bars up to doses of 7 Gy, with a slope of 0.233 +/- 0.001 s(-1) Gy(-1) and an intercept of 1.106 +/- 0.005 Gy. For higher doses, nonlinear behaviour was observed.

Acrylamides↗
PubMed1998

Inverse planning with constraints to generate smoothed intensity-modulated beams.

Highly conformal dose distributions can be generated by intensity-modulated radiotherapy. Intensity-modulated beams (IMBs) are generally determined by inverse-planning techniques designed to maximize conformality. Usually such techniques apply no constraints on the form of the IMBs which may then develop fine-scale modulation. In this paper we present a technique for generating smoother IMBs, which yields a dose distribution almost identical to that without the constraint on the form of the IMBs. The method applies various filters successively at intervals throughout the iterative inverse planning. It is shown that the IMBs so determined using a simple median window filter have desirable properties in terms of increasing the efficiency of delivery by the dynamic multileaf collimator method and may be 'more like conventional beams' than unconstrained, highly modulated IMBs.

Humans↗
PubMed1998

Configuration options for intensity-modulated radiation therapy using multiple static fields shaped by a multileaf collimator.

One-dimensional (1D) intensity-modulated beams (IMBs) can be generated by multiple static fields (MSFs) created by a multileaf collimator (MLC) with the radiation switched off between field re-settings (Bortfeld-Boyer method). Each component irradiation is of equal fluence. This paper presents and analyses the formulae for the number of physically allowed combinations of leaf settings which generate any given IMB. The formulae are general to an IMB with any number of local minima and extend from the well-known N! formula for a single-peaked IMB with N left-leaf (L-leaf) and N right-leaf (R-leaf) positions. A 'combination' is a set of N L-leaf and R-leaf pairings. A 'physically allowed combination' is one in which no L-leaf is paired with an R-leaf to its left. The physically allowed combinations are grouped by specific properties into classes in which the well-known techniques of 'leaf-sweep' and 'close-in' are just two members. Consideration of these properties leads to a new suggestion of the 'forced-baseline' configuration in which the first intensity increment is delivered for the full field width and there remain choices concerning the delivery of the rest of the IMB within which two different possibilities are 'one-out-of-sync leaf-sweep' and 'minimum leaf travel'. The extension to 2D is briefly introduced.

Models, Theoretical↗
PubMed1998

An investigation into the dosimetry of a nine-field tomotherapy irradiation using BANG-gel dosimetry.

BANG-gel dosimetry offers the potential for measuring the dose delivered by a radiotherapy treatment technique, in three dimensions, with high spatial resolution and good accuracy. The ability to measure comprehensively a 3D dose distribution is a major advantage of the gel dosimeter over conventional planar and point-based dosimeter devices, particularly when applied to the verification of complex dose distributions characteristic of intensity-modulated radiotherapy (IMRT). In this paper an in-house manufactured BANG-gel dosimeter was applied to study the dose distributions of two irradiation experiments for which the distributions were known: (i) a dosimetrically simple parallel-opposed irradiation, and (ii) a more complex nine-field 'static tomotherapy' intensity-modulated irradiation delivered with the Nomos MIMiC. The uniform distribution in (i) allowed a study of the magnetic resonance (MR) imaging parameters to achieve an optimal trade-off between noise and image resolution (optimum image resolution for the Siemens 1.5T Vision system was determined to be approximately 0.8 mm2 with a slice thickness of 2 mm). The spatial uniformity of gel sensitivity to radiation was found to depend strongly on the presence of oxygen, which must be eliminated for the gel dosimeter to be of use. The gel dosimeter was found to agree well with predicted dose distributions and accurately measured the steep penumbral fall-off of dose, even after many days, proving its potential for the verification of IMRT distributions. In the nine-field IMRT delivery (ii) the predicted dose was computed by both an in-house 'component-delivery' dose algorithm and the Peacock planning-system dose algorithm. Good agreement was found between the two algorithms despite the latter's omission of the change in penumbral characteristics with aperture-size during delivery, lack of inhomogeneity correction and approximate modelling of leaf leakage. These effects were found to be small for the problem studied. The predicted distribution agreed well with the gel-measured distribution at medium and high doses (50-90% isodose lines) although differences of up to 10% were observed at lower doses (30% isodose line). The gel dosimeter was found to have the potential to verify IMRT distributions but required considerable care to achieve accurate results. Attention was required to achieve uniformity of gel sensitivity (to prevent oxygen contamination), and in the calibration process.

Acrylamide↗
PubMed1998

Configuration options for intensity-modulated radiation therapy using multiple static fields shaped by a multileaf collimator. II: constraints and limitations on 2D modulation.

This paper addresses the technique of using multiple static multileaf-collimator-shaped field components to create a two-dimensional intensity-modulated beam (2D IMB). It addresses the physical constraints on the problem of determining the optimum field-component leaf configurations under the circumstances that (i) the static field components are shaped by leaves alone and (ii) the 2D intensity distribution is delivered by exactly N field components when there are N rising-intensity equal-fluence increments in the 1D channel containing the maximum fluence in the 2D IMB. This corresponds to the least inefficient delivery. In general it is noted that an optimum solution (set of field-component leaf configurations) with zero tongue-and-groove underdose may not exist (depending on the distribution) and an exhaustive search for the set of leaf configurations with the minimum tongue-and-groove underdose is impossible for realistically sized problems. Against this background iterative methods to examine a limited search space are shown to yield an optimum solution with zero tongue-and-groove underdose for certain intensity distributions. These searches are not robust and can be defeated. The problem of finding an optimum solution may be generally insoluble for some 2D IMBs under the conditions (i) and (ii). If, however, a larger number of field components is permitted and/or the accelerator jaws may also be used, in addition to the multileaves, then an optimum solution with zero tongue-and-groove underdose can always be found with lower efficiency.

Biophysical Phenomena↗
PubMed1998

A case study comparing the relative benefit of optimizing beam weights, wedge angles, beam orientations and tomotherapy in stereotactic radiotherapy of the brain.

A treatment-planning case study has been performed on a patient with a medium-sized, convex brain tumour. The study involved the application of advanced treatment-plan optimization techniques to improve on the dose distribution of the 'standard plan' used to treat the patient. The standard plan was created according to conventional protocol at the Royal Marsden NHS Trust, and consisted of a three-field (one open and two wedged) non-coplanar arrangement, with field shaping to the beam's-eye view of the planning target volume (PTV). Three optimized treatment plans were created corresponding to (i) the optimization of the beam weights and wedge angles of the standard plan, (ii) the optimization of the beam orientations, beam weights and wedge angles of the standard plan, and (iii) a full fluence tomotherapy optimization of 1 cm wide (at isocentre), 270 degree arcs. (i) and (ii) were created on the VOXELPLAN research 3D treatment-planning system, using in-house developed optimization algorithms, and (iii) was created on the PEACOCK tomotherapy planning system. The downhill-simplex optimization algorithm is used, in conjunction with 'threshold-dose' cost-function terms enabling the algorithm to optimize specific regions of the dose-volume histogram (DVH) curve. The 'beam-cost plot' tool is presented as a visual aid to the selection of beneficial beam directions. The methods and pitfalls in the transfer of plans and patient data between the two planning systems are discussed. Each optimization approach was evaluated, relative to the standard plan, on the basis of DVH and dose statistics in the PTV and organs at risk (OARs). All three optimization approaches were able to improve on the dose distribution of the standard plan. The magnitude of the improvement was greater for the optimized beam-orientation and tomotherapy plans (up to 15% and 30% for the maximum and mean OAR doses). A smaller improvement was observed in the beam-weight and wedge-angle optimized plan (up to 5% and 10% in the maximum and mean OAR doses). In the tomotherapy plan, difficulty was encountered achieving an acceptable homogeneity of dose in the PTV. This was improved by treating the gross tumour volume (GTV) and (PTV - GTV) regions as separate targets in the inverse planning, with the latter region prescribed a slightly higher dose to reduce edge under-dosing. In conclusion, for the medium-sized convex tumour studied, the tomotherapy dose distribution showed a significant improvement on the standard plan, but no significant improvement over a conventional three-field plan where the beam orientations, beam weights and wedge angles had been optimized.

Adenoma↗
PubMed1998

Generation of discrete beam-intensity modulation by dynamic multileaf collimation under minimum leaf separation constraints.

An algorithm to generate discrete beam-intensity modulation by dynamic multileaf collimation is presented which incorporates constraints on minimum allowed leaf separations. MLC positioning information is derived simultaneously for all leaf pairs and back-up diaphragms as they progress across the field. A feedback mechanism allows corrections to be applied to eliminate potential violations of minimum separation conditions and any underexposure in the interleaf tongue-and-groove region as they are encountered. The resulting motion correctly delivers the intended modulation and is physically realizable. Implementation of the algorithm is described. Results of the algorithm can also alternatively be interpreted as defining a series of static fields to deliver the same modulation.

Algorithms↗
PubMed1998

Autosomal dominant hereditary spastic paraparesis with cognitive loss linked to chromosome 2p.

A family initially considered to have 'pure' autosomal dominant hereditary spastic paraparesis (HSP), was found on neuropsychological testing to have evidence of late onset cognitive impairment. This family showed genetic linkage to the SPG4 locus on chromosome 2p previously reported for pure HSP. Of 56 living members, 44 were examined, 30 of whom were > 30 years of age and 12 members were found to be affected with HSP including four asymptomatic cases. One other family member (III-5), aged 62 years, died prior to this study of a 4-year dementing illness. Neuropsychological assessment of 11 affected members and 11 matched, unaffected, family controls showed no significant differences between the two groups. However, the neuropsychological test profile in four of 11 affected members tested (mean age 47.2 years) and one of 11 family controls (mean age 41.5 years) showed global cognitive impairment. The pattern of cognitive dysfunction was the same for all five family members identified and was similar to that found in subcortical dementia. The presence of cognitive impairment appeared to be related to age and not the severity of the paraplegia. Both the severity of the paraplegia and the age of onset (21-60 years) varied considerably in this family.

Adult↗
PubMed1998

Cognitive impairment in families with pure autosomal dominant hereditary spastic paraparesis.

In the course of a study of a large family with pure autosomal dominant hereditary spastic paraparesis (AD-HSP), mild cognitive impairment was found in older family members. In order to determine if cognitive impairment occurred more frequently in families with pure AD-HSP than normally expected, a case control study of cognitive function in HSP was undertaken. Thirty-one patients, from 12 kindreds with pure AD-HSP, matched with 31 healthy control subjects for age, sex and years of education, were assessed for evidence of cognitive impairment using the Cambridge Cognitive Examination (CAMCOG). Twenty unaffected siblings matched with twenty healthy control subjects were similarly assessed. The total CAMCOG score in the affected group (mean 89.26/107, SD 11.08, 95% confidence interval 85.2-94.49) compared with the control group (mean 96.52/107, SD 5.52, 95% confidence interval 94.49-98.54) was significantly reduced (P = 0.0003). There were also significant abnormalities in three out of the nine subsets including memory (P = 0.0002), language comprehension (P = 0.0166) and language expression (P = 0.0025). The differences between the groups were due to cognitive impairment appearing after the age of 50 years in patients with AD-HSP; CAMCOG scores before this age were similar to control scores. There was also a minor non-significant difference in total CAMCOG score for the unaffected siblings (mean 93.7/107, SD 8.54, 95% confidence interval 89.70-97.70) compared with the control group (mean 97.9/107, SD 4.61, 95% confidence interval 95.7-100.1) (P < 0.02). This study demonstrates that mild cognitive impairment develops after the age of 50 years in patients with pure AD-HSP and is further evidence of degeneration in other systems in this disorder.

Adult↗
PubMed1998

Improvements in prostate radiotherapy from the customization of beam directions.

A methodology for optimizing the beam directions in radiotherapy treatment planning has been developed and tested on a cohort of twelve prostate patients. An optimization algorithm employing a an objective cost function was used, based on beam's-eye-view volumetrics but also employing a simple dose model and biological considerations for organs-at-risk (OARs). The cost function embodies information about the volume of OARs in a single field and their position relative to the planning target volume (PTV). The proximity of the PTV to the surface of the patient is also included. Within the algorithm "importance factor" were used to model the clinical importance of different organs-at-risk so that all organs-at-risk were included in a single objective score. "Gantry-angle-windows" were introduced to restrict the available beam directions. The methodology was applied to twelve prostate patients to determine the optimum beam directions for three-field direction plans. Orientation-optimized and standard treatment plans were compared via measures of tumor control probability (TCP) and normal tissue complication probability (NTCP). Standard plans had fixed beam directions whereas orientation-optimized plans contained beam directions chosen by the algorithm. The beam-weights of both the orientation-optimized and standard plans were optimized using a dose-based simulated annealing algorithm to allow the improvements by optimizing the beam directions to be studied in isolation. The results of the comparison show that optimization of the beam directions yielded better plans, in terms of TCP and NTCP, than the standard plans. When the dose to the isocenter was scaled to produce a rectal NTCP of 1%, the average TCP of the orientation-optimized plans was (5.7 +/- 1.4)% greater than that for the standard plans. In conclusion, the customization of beam directions in the treatment planning of prostate patients using and objective cost function and allowed gantry-angle-windows produces superior three-field direction plans compared to standard treatment plans.

Algorithms↗
PubMed1998

Rapid portal imaging with a high-efficiency, large field-of-view detector.

The design, construction, and performance evaluation of an electronic portal imaging device (EPID) are described. The EPID has the same imaging geometry as the current mirror-based systems except for the x-ray detection stage, where a two-dimensional (2D) array of 1 cm thick CsI(Tl) detector elements are utilized. The approximately 18% x-ray quantum efficiency of the scintillation detector and its 30 x 40 cm2 field-of-view at the isocenter are greater than other area-imaging EPIDs. The imaging issues addressed are theoretical and measured signal-to-noise ratio, linearity of the imaging chain, influence of frame-summing on image quality and image calibration. Portal images of test objects and a humanoid phantom are used to measure the performance of the system. An image quality similar to the current devices is achieved but with a lower dose. With approximately 1 cGy dose delivered by a 6 MV beam, a 2 mm diam structure of 1.3% contrast and an 18 mm diam object of 0.125% contrast can be resolved without using image-enhancement methods. A spatial resolution of about 2 mm at the isocenter is demonstrated. The capability of the system to perform fast sequential imaging, synchronized with the radiation pulses, makes it suitable for patient motion studies and verification of intensity-modulated beams as well as its application in cone-beam megavoltage computed tomography.

Equipment Design↗
PubMed1998

The derivation of tissue-maximum ratio from percentage depth dose requires peak scatter factor to be considered a function of source-to-surface distance.

A formula for the calculation of tissue-maximum ratio (TMR) from percentage depth dose (PDD) and peak scatter factor (PSF) is derived from first principles using a simple geometric model for the case when the field size for PDD and PSF is defined at the surface. The derivation is carried out in two ways: (a) taking field size for PDD and PSF as defined at the depth of maximum dose and then applying a conversion factor, and (b) by a direct derivation. The first of these methods yields a formula which agrees with BJR Supplement 25, but the latter yields a result which differs from it. Numerically, this difference is insignificant, but it has implications for the theoretical basis of the conversion formulae. The difference arises due to the translation of field size from one depth to another when calculating PSF: two different values of source-to-surface distance (SSD) yield two apparently different PSFs for the same size of field at the depth of maximum dose. Disagreements of this type are prevalent throughout the standard conversion formulae given in BJR Supplement 25 when field size for PDD and PSF is defined at the surface rather than at the depth of dose maximum. These disagreements are illustrated here using the conversion of PDD from one SSD to another as an example. The difficulty is overcome by considering PSF to be a function of SSD as well as field size.

Humans↗