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Biomedical subjects

R J Ott

Publications and source records attributed to R J Ott.

At least 19 recordsLinked to original sources
PubMed2003

Scaling images using their background ratio. An application in statistical comparisons of images.

Comparison of two medical images often requires image scaling as a pre-processing step. This is usually done with the scaling-to-the-mean or scaling-to-the-maximum techniques which, under certain circumstances, in quantitative applications may contribute a significant amount of bias. In this paper, we present a simple scaling method which assumes only that the most predominant values in the corresponding images belong to their background structure. The ratio of the two images to be compared is calculated and its frequency histogram is plotted. The scaling factor is given by the position of the peak in this histogram which belongs to the background structure. The method was tested against the traditional scaling-to-the-mean technique on simulated planar gamma-camera images which were compared using pixelwise statistical parametric tests. Both sensitivity and specificity for each condition were measured over a range of different contrasts and sizes of inhomogeneity for the two scaling techniques. The new method was found to preserve sensitivity in all cases while the traditional technique resulted in significant degradation of sensitivity in certain cases.

Algorithms↗
PubMed2003

Multicellular dosimetry in voxel geometry for targeted radionuclide therapy.

A software package to investigate absorbed doses and dose-rates at the cellular and multicellular scale has been developed that considers two- and three-dimensional activity distributions and makes use of analytical representations of the point-dose kernels for (131)I, (32)P, and (90)Y. This software allows cell assemblies to be simulated by definition of the number, size, and geometry of cells and their nuclei, and radionuclide uptake can be specified to occur within the nucleus, the cytoplasm, at the membrane, or within the extracellular space. The software has been validated at a cellular scale by comparison with results obtained using spherical geometry, as found in the literature. At a multicellular scale, comparisons were made with a Monte Carlo simulation in voxel geometry. The software has been designed to work within a user-defined voxel geometry. This geometry is useful not only to simulate complex cell assemblies and realistic heterogeneous radionuclide distributions, but will also allow the use of histological and autoradiographic data. Absorbed dose distributions for a single cell calculated using this code varied significantly with activity localization within the cell, and to a lesser extent, with the cellular geometry. At a multicellular level, a two-dimensional heterogeneous activity distribution inferred from a two-dimensional image of a slice throughout a spheroid was used to calculate a dose-rate distribution. This resulted in a heterogeneous dose-rate delivery even for longer-range radionuclides such as (90)Y and (32)P.

Absorption↗
PubMed2001

Continuous angiotensin II infusion increases tumour: normal blood flow ratio in colo-rectal liver metastases.

Insufficient blood flow within colo-rectal hepatic metastases is a factor which may limit drug delivery to, and thus the response of, these tumours to regional chemotherapy. Loco-regional flow may be manipulated pharmacologically to enhance the tumour blood flow relative to that of the normal liver. However, as yet, only transient effects have been studied. Patients receiving regional chemotherapy for unresectable hepatic disease were given a 45 min regional infusion of the vasoconstrictor Angiotensin II. Intrahepatic blood flow distribution was assessed serially by Positron Emission Tomography (PET) imaging together with the trapping tracer copper(II) pyruvaldehyde bis(N-4-methylthiosemicarbazone) (Cu-PTSM) labelled using copper-62. Eleven lesions in nine patients were studied, with no adverse effects. Prior to Angiotensin II administration tumour blood flow was generally found to be greater than that of liver (10/11 lesions; 8/9 patients; median TNR 1.3, iqr 0.9-2.5). A significant increase in relative flow to tumour was seen in response to 10 min Angiotensin II infusion in most cases (7/11 lesions; 7/9 patients; median TNR 2.1, iqr 1.4-4.1; P = 0.008), which appeared to be sustained throughout the 45 min infusion period (median TNR 1.85, iqr 1.3-3.8; P = 0.03). These effects were accompanied by transient elevation of mean arterial pressure, but no change in pulse rate. These observations suggest that prolonged regional vasoconstrictor administration could prove useful in the management of unresectable colo-rectal hepatic metastases, and that further development of vascular manipulation to enhance tumour targeting and drug delivery is warranted.

Angiotensin II↗
PubMed2001

2-Amino-6-arylsulfonylbenzonitriles as non-nucleoside reverse transcriptase inhibitors of HIV-1.

A series of 2-amino-5-arylthiobenzonitriles (1) was found to be active against HIV-1. Structural modifications led to the sulfoxides (2) and sulfones (3). The sulfoxides generally showed antiviral activity against HIV-1 similar to that of 1. The sulfones, however, were the most potent series of analogues, a number having activity against HIV-1 in the nanomolar range. Structural-activity relationship (SAR) studies suggested that a meta substituent, particularly a meta methyl substituent, invariably increased antiviral activities. However, optimal antiviral activities were manifested by compounds where both meta groups in the arylsulfonyl moiety were substituted and one of the substituents was a methyl group. Such a disubstitution led to compounds 3v, 3w, 3x, and 3y having IC50 values against HIV-1 in the low nanomolar range. When gauged for their broad-spectrum antiviral activity against key non-nucleoside reverse transcriptase inhibitor (NNRTI) related mutants, all the di-meta-substituted sulfones 3u-z and the 2-naphthyl analogue 3ee generally showed single-digit nanomolar activity against the V106A and P236L strains and submicromolar to low nanomolar activity against strains E138K, V108I, and Y188C. However, they showed a lack of activity against the K103N and Y181C mutant viruses. The elucidation of the X-ray crystal structure of the complex of 3v (739W94) in HIV-1 reverse transcriptase showed an overlap in the binding domain when compared with the complex of nevirapine in HIV-1 reverse transcriptase. The X-ray structure allowed for the rationalization of SAR data and potencies of the compounds against the mutants.

Anti-HIV Agents↗
PubMed2001

62Cu-PTSM and PET used for the assessment of angiotensin II-induced blood flow changes in patients with colorectal liver metastases.

The aim of this study was to establish a quantitative positron emission tomography (PET) method for investigating angiotensin II (AII)-induced changes in blood flow distribution in the liver. This was in order to evaluate the role of vascular manipulation applied to locoregional chemotherapy treatment in patients with colorectal liver metastases. The tracer selected was copper-62 (II) pyruvaldehyde bis-(N4-methyl)thiosemicarbazone (62Cu-PTSM), which exhibits high first-pass extraction and tissue retention following intra-arterial administration. The short half-life of the tracer and its availability from a 62Zn/62Cu generator enabled short-interval repeat PET scans on patients in a single imaging session. Distribution of tracer within the liver was imaged in a single view using a PET camera with rotating large-area detectors. By optimisation of the acquisition protocol, it was possible to acquire sufficient data to produce good-quality images and to quantify tracer uptake with an accuracy of <10%. Reproducibility of the imaging method was assessed in a single patient in whom three consecutive 62Cu-PTSM PET scans were obtained, and in whom no vascular manipulation was performed. Sets of scans (before, during and immediately after a 45-min AII infusion) were obtained in nine patients to assess blood flow changes associated with prolonged vascular manipulation. Significant individual responses, varying in both the magnitude and the duration of flow change, were observed in the majority of cases (7/11 lesions; 7/9 patients). These findings illustrate the potential of 62Cu-PTSM and PET for pharmacological studies. The wide range of individual patient responses to AII infusion suggests that PET blood flow assessment would be of value for selecting patients in whom this procedure may be effective.

Algorithms↗
PubMed2001

Effects of fenofibrate on lipid parameters in obese rhesus monkeys.

Fenofibrate is a member of the fibrate class of hypolipidemic agents used clinically to treat hypertriglyceridemia and mixed hyperlipidemia. The fibrates were developed primarily on the basis of their cholesterol and triglyceride lowering in rodents. Fibrates have historically been ineffective at lowering triglycerides in experimentally-induced dyslipidemia in nonhuman primate models. The spontaneously obese rhesus monkey is a well-recognized animal model for the study of human obesity and type 2 diabetes, and many of these monkeys exhibit naturally occurring lipid abnormalities, including elevated triglycerides and low HDL cholesterol (HDL-C), similar to patients with type 2 diabetes. To explore whether the obese rhesus model was predictive of the lipid lowering effects of fibrates, we evaluated fenofibrate in six hypertriglyceridemic, hyperinsulinemic, nondiabetic animals in a 20-week, dose-escalating study. The study consisted of a 4-week baseline period, two treatment periods of 10 mg/kg twice daily (b.i.d) for 4 weeks and 30 mg/kg b.i.d. for 8 weeks, and a 4-week washout period. Fenofibrate (30 mg/kg b.i.d) decreased serum triglycerides 55% and LDL-C 27%, whereas HDL-C increased 35%. Apolipoproteins B-100 and C-III levels were also reduced 70% and 29%, respectively. Food intake, body weight, and plasma glucose were not affected throughout the study. Interestingly, plasma insulin levels decreased 40% during the 30 mg/kg treatment period, suggesting improvement in insulin sensitivity. These results support the use of obese rhesus monkey as an excellent animal model for studying the effects of novel hypolipidemic agents, particularly agents that impact serum triglycerides and HDL-C.

Amino Acid Sequence↗
PubMed2000

Are 18fluorodeoxyglucose positron emission tomography and magnetic resonance imaging useful in the prediction of relapse in lymphoma residual masses?

Treatment of both Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL) frequently results in a residual mass visible radiologically. Such patients may receive radiotherapy unnecessarily because the residual mass may represent benign fibrotic tissue rather than residual active lymphoma. Radiotherapy has been shown to have significant short and more worrying long-term toxicity. Refining the criteria for its use would be a major advance. A number of clinical investigations have been evaluated to more accurately determine the nature of such lesions, including erythrocyte sedimentation rate (ESR), magnetic resonance imaging (MRI) and high-dose gallium-67 scanning (HDGS) but none has proven utility. 18[F]-fluorodeoxyglucose positron emission tomography (FDG-PET) is an imaging technique that has been shown to be useful in distinguishing fibrosis from residual active disease in solid tumours. The aim of this study was to compare FDG PET and MRI in the assessment of residual masses following treatment for lymphoma. Patients with NHL/HD who had a residual mass following chemotherapy were eligible for this study. Patients had a combination of MRI and/or PET. All scans were completed within 5 months of the end of treatment. Patients were followed-up for relapse. 56 patients had an MRI scan, 24 had a PET scan and 22 patients had both investigations. Overall sensitivity and specificity, respectively, were for MRI 45% and 74%, PET 50% and 69%, and PET/MRI concurring 50% and 67%. There was a trend for improved relapse-free survival (RFS) with a negative result of both MRI and PET, but this was not statistically significant. The predictive value for both tests failed to reach statistical significance. Subgroup analysis suggests that PET may be better at predicting relapse in patients with NHL, especially those with masses above the diaphragm. There is no convincing evidence that either MRI or PET or the combination can reliably predict relapse within residual masses after treatment for lymphoma. A negative PET scan however appears to be more informative than a positive result and may well aid clinical decision making. There are a number of factors that may produce false-positive results, including post-treatment inflammatory changes, the sensitivity of the test in the setting of minimal residual disease and the heterogeneity of the histological subtypes studied. A negative PET (or MRI) result in lymphoma residual masses following therapy may negate the necessity for further therapy such as chemotherapy or radiotherapy and their concomitant toxicities.

Adolescent↗
PubMed2000

FDG-PET in the prediction of survival of patients with cancer of the pancreas: a pilot study.

Carcinoma of the pancreas is an aggressive tumour with an extremely poor prognosis. Recent studies have shown that chemotherapy can improve survival as well as quality of life. Since the prognosis is generally poor, the identification of early responders to chemotherapy is important to avoid unnecessary toxicity in patients who are not responding. Response assessment by conventional radiographic methods is problematical because treatment induces fibrosis and makes tumour measurements difficult. The aim of this pilot study was to assess 18-fluoro-deoxy-glucose positron emission tomography (FDG-PET) as an early marker of the benefit of chemotherapy. Eleven patients with histologically proven adenocarcinoma of the pancreas were treated with protracted venous infusional 5-fluorouracil (PVI 5-FU) alone or PVI 5-FU and mitomycin C (MMC). FDG-PET scans were performed prior to and at 1 month following the commencement of chemotherapy. FDG uptake was compared with the tumour dimensions measured on a computer tomographic (CT) scan. Patients were followed up for relapse, death and symptomatic response. Three of the 11 patients had no measurable FDG uptake prior to chemotherapy. Of the eight patients who had measurable uptake prior to treatment, seven had a reduction in uptake at 1 month. Six out of the 11 patients had no measurable FDG uptake at 1 month. The overall survival (OS) in these patients ranged from 124 to 1460 days, with a median of 318.5 days. This was superior in comparison to patients who had residual FDG uptake at 1 month (median survival 318.5 days vs 139 days; P = 0.034) and there was a trend to improved symptoms (84% [5/6] vs 20% [1/5]; P = 0.13). There was no statistically significant correlation between best CT response and FDG uptake at 1 month. These results suggest that the absence of FDG uptake at 1 month following chemotherapy for carcinoma of the pancreas is an indicator of improved overall survival. This suggests that FDG-PET may be superior to response assessment by conventional radiographic methods and FDG-PET may have the potential to help make difficult treatment decisions in the management of pancreatic cancer. Larger prospective studies are required to confirm this finding.

Antineoplastic Agents↗
PubMed2000

Classification of reflectance spectra from pigmented skin lesions, a comparison of multivariate discriminant analysis and artificial neural networks.

Successful treatment of skin cancer, especially melanoma, depends on early detection, but diagnostic accuracy, even by experts, can be as low as 56% so there is an urgent need for a simple, accurate, non-invasive diagnostic tool. In this paper we have compared the performance of an artificial neural network (ANN) and multivariate discriminant analysis (MDA) for the classification of optical reflectance spectra (320 to 1100 nm) from malignant melanoma and benign naevi. The ANN was significantly better than MDA, especially when a larger data set was used, where the classification accuracy was 86.7% for ANN and 72.0% for MDA (p < 0.001). ANN was better at learning new cases than MDA for this particular classification task. This study has confirmed that the convenience of ANNs could lead to the medical community and patients benefiting from the improved diagnostic performance which can be achieved by objective measurement of pigmented skin lesions using spectrophotometry.

Algorithms↗
PubMed2000

Spectrophotometric assessment of pigmented skin lesions: methods and feature selection for evaluation of diagnostic performance.

This study documents the optical reflectance characteristics of pigmented skin lesions and evaluates their potential for improving the differential diagnosis of malignant melanoma from benign pigmented skin lesions. Optical reflectance spectra in the wavelength range 320-1100 nm were obtained from 121 lesions already selected by expert dermatologists as suspicious of malignancy. Characteristic differences in spectra from benign and malignant lesions were studied. Feature extraction showed significant differences between lesion groups classified by histology. Seven of the most relevant features were used in the discriminant analysis of reflectance spectra from 15 melanoma and 32 compound naevi which resulted in a sensitivity of 100% and specificity of 84.4% when compared with histology. This simple objective technique appears to perform as well as the expert dermatologist and may improve the diagnostic accuracy of non-specialists such as trainees and GPs. Further prospective clinical study of reflectance spectrophotometry in a larger patient group is now required.

Adolescent↗
PubMed2000

The performance of a CCD digital autoradiography imaging system.

Autoradiography is a widely used technique for imaging trace quantities of radioactivity within biological samples, conventionally using photographic film. This method produces images with high spatial resolution, but it suffers from very low sensitivity and poor dynamic range. Digital autoradiography systems with greatly improved sensitivity and linearity are commercially available, but the spatial resolution is usually much less than that achieved using film. We report here the design, construction and characterization of a novel digital autoradiography system based on scientific-grade charged coupled devices (CCDs). Images of x-ray and beta emissions from radionuclides commonly used in autoradiography show that the system can perform high-speed quantitative imaging with a spatial resolution of approximately 30, microm. Using a frame by frame acquisition method the dynamic range is shown to be at least three orders of magnitude. The absolute detection efficiency is comparable to the best of the currently available digital systems. CCD images of 125I and 14C radioisotope distributions in tissue samples are superior to the equivalent film images and have been acquired in 1-10% of the time.

Animals↗
PubMed1999

A CCD-based system for the detection of DNA in electrophoresis gels by UV absorption.

A method and apparatus for the detection and quantification of large fragments of unlabelled nucleic acids in agarose gels is presented. The technique is based on ultraviolet (UV) absorption by nucleotides. A deuterium source illuminates individual sample lanes of an electrophoresis gel via an array of optical fibres. As DNA bands pass through the illuminated region of the gel the amount of UV light transmitted is reduced because of absorption by the DNA. During electrophoresis the regions of DNA are detected on-line using a UV-sensitive charge coupled device (CCD). As the absorption coefficient is proportional to the mass of DNA the technique is inherently quantitative. The mass of DNA in a region of the gel is approximately proportional to the integrated signal in the corresponding section of the CCD image. This system currently has a detection limit of less than 1.25 ng compared with 2-10 ng for the most popular conventional technique, ethidium bromide (EtBr) staining. In addition the DNA sample remains in its native state. The removal of the carcinogenic dye from the detection procedure greatly reduces associated biological hazards.

DNA↗
PubMed1998

Intercomparison of four reconstruction techniques for positron volume imaging with rotating planar detectors.

Four reconstruction techniques for positron volume imaging have been evaluated for scanners based on rotating planar detectors using measured and simulated data. The four techniques compared are backproject then filter (BPF), the 3D reprojection (3D RP) method for 3D filtered backprojection (FBP), Fourier rebinning (FORE) in conjunction with 2D FBP (FORE + 2D FBP) and 3D ordered subsets expectation maximization (3D OSEM). The comparison was based on image resolution and on the trade-off between contrast and noise. In general FORE + 2D FBP offered a better contrast-noise trade-off than 3D RP, whilst 3D RP offered a better trade-off than BPF. Unlike 3D RP, FORE + 2D FBP did not suffer any contrast degradation effect at the edges of the axial field of view, but was unable to take as much advantage from high-accuracy data as the other methods. 3D OSEM gave the best contrast at the expense of greater image noise. BPF, which demonstrated generally inferior contrast-noise behaviour due to use of only a subset of the data, gave more consistent spatial resolution over the field of view than the projection-data based methods, and was best at taking full advantage of high-accuracy data.

Computer Simulation↗
PubMed1998

Fast accurate iterative reconstruction for low-statistics positron volume imaging.

A fast accurate iterative reconstruction (FAIR) method suitable for low-statistics positron volume imaging has been developed. The method, based on the expectation maximization-maximum likelihood (EM-ML) technique, operates on list-mode data rather than histogrammed projection data and can, in just one pass through the data, generate images with the same characteristics as several ML iterations. Use of list-mode data preserves maximum sampling accuracy and implicitly ignores lines of response (LORs) in which no counts were recorded. The method is particularly suited to systems where sampling accuracy can be lost by histogramming events into coarse LOR bins, and also to sparse data situations such as fast whole-body and dynamic imaging where sampling accuracy may be compromised by storage requirements and where reconstruction time can be wasted by including LORs with no counts. The technique can be accelerated by operating on subsets of list-mode data which also allows scope for simultaneous data acquisition and iterative reconstruction. The method is compared with a standard implementation of the EM-ML technique and is shown to offer improved resolution, contrast and noise properties as a direct result of using improved spatial sampling, limited only by hardware specifications.

Image Processing, Computer-Assisted↗
PubMed1997

Three-dimensional dosimetry for intralesional radionuclide therapy using mathematical modeling and multimodality imaging.

UNLABELLED: A method of dosimetry is described that quantifies the three-dimensional absorbed-dose distribution resulting from an intralesional administration of a radiolabeled monoclonal antibody, allowing for both spatial and temporal heterogeneity of distribution of the radionuclide and without the need for a calibration scan. METHODS: A mathematical model was developed to describe the distribution of activity as a function of time resulting from infusion at a single point within the solid component of a tumor. The parameters required for this model are either known directly or may be obtained from SPECT image data registered to computed tomography. Convolution of this distribution with a point-source dose kernel enabled the three-dimensional absorbed-dose distribution to be obtained. RESULTS: This method was applied to a set of patient data acquired in the course of a clinical study performed at our center, and dose profiles and dose-volume histograms were produced. It was shown that the three-dimensional distribution of dose was significantly nonuniform. CONCLUSION: Initial results suggest that this method offers a means of determining the absorbed dose distribution within a tumor resulting from intralesional infusion. This method extends the Medical Internal Radiation Dose computation, which, in these circumstances, would make erroneous assumptions. Furthermore, it will enable individual patient treatment planning and optimization of the parameters that are within the clinician's control.

Humans↗
PubMed1996

Imaging technologies for radionuclide dosimetry.

Targeted radionuclide therapy is becoming an increasingly popular treatment modality as an alternative or as an adjunct to external beam radiotherapy and chemotherapy. The present method of dosimetry based on the MIRD system requires measurements of the concentration of the radionuclide in the target and risk tissues and the effective half-life of the radionuclide in these tissues. Radionuclide imaging techniques including planar scintigraphy, rectilinear scanning, single-photon emission computed tomography and positron emission tomography have all been used to provide data from which this information can be obtained. Additionally anatomical imaging has been used to aid these estimates. This paper reviews the application of imaging technology and methodology to radionuclide dosimetry.

Gamma Cameras↗