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Biomedical subjects

M Partridge

Publications and source records attributed to M Partridge.

At least 55 records · Page 3Linked to original sources

Optical scattering in camera-based electronic portal imaging.

An investigation of scintillation light scattering within camera-based electronic portal imaging devices is presented. A simple analytical scatter model is adapted for the precise geometries of two different camera-based imaging systems and the results of modelling and experimental measurements are compared. The results of the study strongly suggest that the main source of optical scattering is multiple reflection between the scintillation screen and 45 degree mirror in both systems. The scattered light has a highly non-uniform distribution, which is strongly dependent upon field size. For large radiation fields the scatter contribution can be over 20% of the primary signal scintillation light intensity in the centre of the field. A purely optical method of removing the scattered light signal using a louvre grid on the surface of the scintillation screen is then presented and experimentally demonstrated to be effective.

Diagnostic Imaging↗

Radiological thickness measurement using a liquid ionization chamber electronic portal imaging device.

We present a method of calibrating the Portal Vision electronic portal imaging device to obtain radiological thickness maps for compensator design. In this method, coefficients are derived to describe the relationship between intensity and thickness for a set of water-equivalent blocks. The effects of four parameters were studied: (a) The dose response of the system was measured and found to be describable by a square-root function. (b) The calibration data and images were taken with a wedge in situ. The effects of using different wedges and different wedge orientations were investigated. The intrinsic accuracy of the accelerator/imager system was found to be 1.9 mm, for both 15 degrees and 30 degrees wedges. Changing the wedge orientation between calibration and imaging and rotating the calibration coefficients accordingly led to an error of 3.5 mm. (c) The variation in detector response with gantry angle was measured and corrected. The residual error in this process was 2.4 mm. (d) The use of a model to correct the effects of imaging with different field sizes was investigated and found to yield a residual error of 2.9 mm. The overall error in image calibrations was approximately 4 mm or 2% in dose. This is considered to be sufficiently small for the intended use of designing compensators for tangential breast irradiation.

Diagnostic Imaging↗

Clinical implementation of a computer controlled milling machine for compensating filter production.

The procedures required for the clinical implementation of a computer controlled milling machine for producing compensators for breast radiotherapy are described. Moulds are cut in a rigid polymer foam block and filled with stainless-steel granulate. Quality assurance procedures are described for ensuring that the compensators produced are consistent and accurate. Relative and absolute dosimetric measurements are presented showing that the compensators are accurate to better than 1% and demonstrate the technique to be clinically acceptable.

Computer-Aided Design↗

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↗

Practical implementation of compensators in breast radiotherapy.

BACKGROUND AND PURPOSE: A method of using electronic portal imaging to design compensators for tangential breast irradiation has been developed. We describe how this has been implemented. MATERIALS AND METHODS: The compensator design method generates wedged and unwedged beam weights, in conjunction with templates for multiple lead-sheet compensators and pseudo-CT outlines. The latter describe the breast and lung profiles in a set of transverse slices. The layers of the compensator and pseudo-CT outlines are transferred to a treatment planning system for verification. The accuracy of the planning system for the high transmission blocks used to describe the compensators has been verified using a plotting tank system. Dose volume histogram data and transaxial and sagittal plan slices have been compared for both standard and compensated treatments for a sample set of five patients. RESULTS: The planning system predicted the dose at depths of 1.5 and 5 cm to within 2% for the compensators tested. The biggest source of discrepancy was a consequence of the planning system requiring blocks to have integer percentage transmission. For all patients studied, the compensated treatment resulted in a significant reduction in the percentage volume outside the 95-105% dose, with an average reduction of 10.2%. The percentage volume outside the 95-107% dose was also reduced by typically 3.4%. The implementation was found to yield a convenient automatic method of designing compensators using electronic portal imaging and verifying the results using a planning system. CONCLUSIONS: These results indicate that this method of implementation can be used in practice. The dosimetric accuracy of the treatment planning system is limited by the requirement that blocks should be of integer transmission, but this effect is small.

Breast Neoplasms↗

Allelic imbalance at chromosomal loci implicated in the pathogenesis of oral precancer, cumulative loss and its relationship with progression to cancer.

A microsatellite assay was used to screen 31 potentially malignant oral lesions presenting as leukoplakia and erythroplakia, with histological evidence of dysplasia, for genetic abnormalities at loci which frequently show allelic imbalance when oral squamous cell carcinomas (SCC) are examined. The microsatellite and restriction fragment length polymorphism (RFLP) markers selected were at 3p21, 8p21-23, 9p21 and included sequences within the Rb (13q14.2), p53 (17p13.1) and DCC (18q21.1) tumour suppressor genes. 8 patients subsequently developed an invasive tumour at the same site, or within 2 cm of the premalignant lesion. A further 8 patients developed SCC at a distant site. Seventy-seven per cent (24/31) of these potentially malignant lesions showed allelic imbalance (AI) and 55% (17/31) of cases showed microsatellite instability (msi). The probability of developing SCC was much greater for patients with lesions showing AI at two or more relevant loci (P = 0.008 by the logrank test) than the group with AI at fewer loci. The estimated probability of development of SCC in this group by 5 years was 73% (95% Cl: 50-92%). This suggests that determining the number of genetic abnormalities in a potentially malignant lesion can help identify patients with true precancers who should be followed closely to ensure that they receive chemoprevention and appropriate advice to limit risk factors, and to allow the early detection of invasive lesions.

Adult↗

The practical implementation of a scatter model for portal imaging at 10 MV.

A detailed validation of a physical model for scattered radiation in portal images at 10 MV is presented. The ratio of the signal due to scattered radiation to the signal due to primary radiation (SPR) in an electronic portal image is defined. A simple physical model for SPR on the central axis (SPR*) was presented by Swindell and Evans for 6 MV and validated for field sizes up to 320 cm2. In this paper, the model is extended to 10 MV and validated for field sizes up to 625 cm2. The model is first compared with Monte Carlo modelled data for field areas A from 40 to 320 cm2, scatterer thicknesses d of 5 to 35 cm water and scatterer to detector distances L2 of 40 to 100 cm. The physical model has one free parameter, which is fitted empirically using these data. Second, experimental measurements are performed with A from 40 to 625 cm2, d from 4.6 to 27.4 cm and L2 fixed at 100 cm. The root mean square (rms) difference between the physical model and the Monte Carlo calculations was less than 0.001 for all L2 greater than 60 cm. Agreement between experimentally measured and physically modelled data amounts to a radiological thickness error of at best 0.7 mm in 273.6 mm and at worst 0.4 in 45.6 mm. The model performs equally well at all field sizes tested. This study shows that the Swindell and Evans SPR* model is accurate at 10 MV for L2 greater than 60 cm for all A up to 625 cm2.

Biophysical Phenomena↗

Linear accelerator output variations and their consequences for megavoltage imaging.

An experimental study of radiation output intensity fluctuations of a Philips SL25 linear accelerator is presented. Measurements are obtained using an electronic portal imaging device, and the consequences of the measured fluctuations for various different applications of megavoltage imaging including portal imaging, transit dosimetry and megavoltage computed tomography (MVCT) are discussed with examples. Fluctuations in output of +/- 0.7% (1 SD) are seen on every radiation pulse after photon noise and uncertainties caused by the detection system have been accounted for. Large fluctuations are also seen during the initial beam stabilization period (15%), during normal accelerator operation after the beam has been on for more than 1 min (4.5%) and during are therapy as a repeatable function of gantry angle (9%). Such output intensity fluctuations are shown to produce image artifacts in portal imaging devices with scanned detector readout and can also produce systematic errors in detector calibration that would lead to uncertainty in transit dose calculations. The propagation of these intensity fluctuations through MVCT image reconstruction is shown to produce ring artifacts in the reconstructed image. Sample portal and MVCT images are presented. All observed fluctuations in accelerator output are well within the manufacturer's specifications and do not affect the total dose delivered during normal treatment. Finally, megavoltage imaging is shown to be a powerful tool for accelerator quality assurance and treatment verification.

Calibration↗

Independent verification using portal imaging of intensity-modulated beam delivery by the dynamic MLC technique.

The use of intensity-modulated radiation fields in radiotherapy treatment has been shown to have the potential to deliver highly conformal dose distributions. One technique for delivering these intensity-modulated beams is a computerized dynamic multileaf collimator (MLC). A major current impediment to the development of dynamic MLC therapy is verification of these highly complex treatments. Electronic portal imaging is shown here to be a solution to this verification problem. Experimental results are presented showing that leaf penumbra measured with a portal imager can be used to accurately define the positions of moving leaves. The random error in these leaf positions is compared with mean leaf positions along each leaf bank and specified leaf positions at prescription control points to check mechanical performance. Individual leaves are also checked for systematic motion errors. All leaf positions are found to be well within the manufacturer's specifications at all times. Finally, integral intensity images are presented that can be related to the dose distribution delivered. Portal imaging is shown to have the potential to become a valuable tool for the verification of dynamic MLC irradiation.

Biophysical Phenomena↗

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↗

Expression of retinoic acid receptors in normal, dysplastic and malignant oral epithelia.

Chemoprevention with retinoic acid (RA) derivatives may reduce the incidence of transformation of potentially malignant oral lesions, and help prevent development of second primary tumours in the upper aerodigestive tract. At present, little is known about the mechanisms by which RA derivatives modify cell proliferation and differentiation. RA interacts with two classes of nuclear receptors: the retinoic acid receptors (RARs) and retinoid X receptors (RXRs). We have used immunohistology to localise these receptors on normal epidermis and oral mucosa. The distribution of RAR and RXR suggests that RA may exert complex growth regulatory effects on oral mucosa. Increased levels of RAR and RXR, together with alterations in the patterns of expression of these receptors, were seen when dysplastic and malignant epithelia were compared to normal oral mucosa. These findings suggest that expression of RAR and RXR receptors is modulated in epithelia showing altered growth regulation.

Carcinoma, Squamous Cell↗

Field cancerisation of the oral cavity: comparison of the spectrum of molecular alterations in cases presenting with both dysplastic and malignant lesions.

Dysplastic lesions and invasive oral squamous cell carcinoma (SCC) from patients with field change were screened by restriction fragment length polymorphism (RFLP) and microsatellite assay. All tumours contained more genetic changes than the matched dysplasia which are likely to represent progression. Four of the 15 dysplastic lesions harboured the same abnormalities detected in the tumour and some paired lesions showed identical novel microsatellite alleles. The finding of identical 'genetic fingerprints' in dysplastic lesions and invasive carcinoma from the same patient provides strong evidence that these dysplasias are precursor lesions and that multiple lesions have probably arisen due to transfer of the progeny of an altered cell. Eight of the 15 dysplastic lesions showed alterations which were not present in the matched cancer, showing that evolution of subclones, or fusion of multiple clones also occurs. A further case showed loss of different alleles in the paired samples. These findings highlight the complexity of the genetic abnormalities present in the mucosa of patients with field change and suggests that the origin of these altered foci may be diverse.

Adult↗

An electronic portal imaging device for transit dosimetry.

An electronic portal imaging device has been designed and constructed. It consists of an array of 128 CsI scintillation crystals coupled to photodiodes which is scanned across the field in 4 seconds. The linac is operated at a dose rate of 400 cGy min-1 and the dose delivered for image acquisition is approximately 27 cGy. The data acquisition controller is a stand-alone STE computer located within the scan arm. Sample images are presented showing contrast and spatial resolution of the system together with a humanoid phantom image and a clinical image of a breast cancer patient. The phantom images show the detector has a contrast resolution of 0.3% (at 15 mm diameter) and a spatial resolution of 2.5-3.2 mm. Images of uniform Perspex blocks have also been calibrated for thickness, indicating the system can measure radiological thickness to an accuracy of 2-3 mm of water. These results indicate the detector may be used for transit dosimetry applications including compensator design.

Biophysical Phenomena↗

Morpholino and phosphorothioate antisense oligomers compared in cell-free and in-cell systems.

Morpholino and phosphorothioate (S-DNA) antisense oligos were compared in both cell-free and in-cell translation systems. In the most stringent test of specificity in the cell-free system, a globin-targeted S-DNA oligo was found to inhibit its target sequence at concentrations of 10 nM and above, but the sequence-specific component of this inhibition dropped below 50% at concentrations of 100 nM and above. A corresponding Morpholino oligo achieved even higher inhibition at 10 nM, but in contrast to the S-DNA, with the Morpholino, the sequence-specific component of this inhibition remained above 93% at a concentration of 3000 nM. In this same cell-free test system, several S-DNA oligos exhibited substantial undesired nonantisense effects at concentrations of 300 nM and above, whereas corresponding Morpholino oligos exhibited little or no nonantisense activity through a concentration of 3000 nM. In scrape-loaded HeLa cells, both globin-targeted and HBV-targeted S-DNAs (both antisense and control oligos) generally failed to achieve significant translational inhibition at extracellular concentrations up to 3000 nM. In contrast, the Morpholino oligos achieved effective and specific translational inhibition at extracellular concentrations ranging from 30 nM to 3000 nM.

Animals↗

Expression of bFGF, KGF and FGF receptors on normal oral mucosa and SCC.

Fibroblast growth factors (FGFs) are involved in the transmission of signals between the epithelia and connective tissue, and influence epidermal growth and differentiation. They are thought to be important in the restoration of normal tissues after injury and aberrant expression may also play a role in tumorigenesis. However, no information is available on the nature of cells within oral mucosa which synthesise and/or respond to FGFs. We have screened normal oral mucosa and oral squamous cell carcinoma (SCC) for expression of bFGF by immunohistology and northern analysis and used RT-PCR to look for transcripts for KGF and the high-affinity FGF receptors FGFR1 and FGFR2. Transcripts for bFGF were detected in normal and malignant oral mucosa and KGF within connective tissue elements. The predominant FGF receptor detected in the epidermis and oral mucosa was FGFR2 which binds KGF with greater affinity than bFGF. Production of KGF by connective tissue components and synthesis of the high-affinity KGF receptor, FGFR2, by oral keratinocytes provides circumstantial evidence for a paracrine growth control loop with KGF synthesised within the lamina propria or tumour stroma influencing the proliferation and maturation of both normal oral epithelium and SCC.

Base Sequence↗

The role of angiogenesis in the spread of oral squamous cell carcinoma.

Microvessels were counted in 41 primary oral squamous cell carcinomas using JC70 antibody to PECAM (CD31). The counts were compared with clinical and pathological indicators of tumour behaviour including lymph node status, tumour stage, type of histological differentiation, size and velocity of tumour growth. Tumour microvessel counts correlated with lymph node metastasis (p < 0.001). This association was independent of tumour size, velocity and type of histological differentiation and when all the variables were analysed by multivariate analysis only vascular count showed a significant association with lymph node metastasis.

Carcinoma, Squamous Cell↗

Frequent gene deletions in potentially malignant oral lesions.

Some oral cancers are preceded by premalignant lesions which include leucoplakia and erythroplakia. At present there are no reliable markers to identify lesions that may progress to malignancy. We have analysed 30 potentially malignant oral lesions for deletions at chromosomal regions that harbour tumour-suppressor genes for oral cancer. A total of 16 of 30 cases (53%) showed loss of heterozygosity (LOH) or allele imbalance at TP53, DCC, 3p21.3-22.1 or 3p12.1-13. These genetic alterations were detected in dysplastic lesions but not in histologically normal mucosa and may be early events in the carcinogenic process. A total of 64% of dysplastic lesions that recurred during the study showed LOH or allele imbalance in the initial biopsy and the number of genetic abnormalities increased in the tumours that developed. This type of molecular profiling may help to identify patients with lesions that may recur or acquire additional genetic events and progress to malignancy.

Adult↗