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Biomedical subjects

M A Flower

Publications and source records attributed to M A Flower.

At least 19 recordsLinked to original sources

Anatomically derived attenuation coefficients for use in quantitative single photon emission tomography studies of the thorax.

Elimination of errors due to poor attenuation correction is an essential part of any quantitative single photon emission tomography (SPET) technique. Attenuation coefficients (mu Tc) for use in attenuation correction of SPET data were determined using technetium 99m and cobalt 57 flood sources and using topographical information obtained from computed tomography (CT) scans and magnetic resonance (MR) images. In patients with carcinoma of the bronchus, the mean attenuation coefficient for 99mTc was 0.096 cm-1 when determined across a transverse section of the thorax at the level of the tumour by means of a 57Co flood source (13 patients) and 0.093 and 0.074 cm-1 as determined from CT scans for points in the centre of the tumour and contralateral normal lung, respectively (21 patients). In 18 patients with breast tumours, the mean attenuation coefficient for 99mTc was 0.110 and 0.076 cm-1 when determined from MRI cross-sections for points in the centre of the tumour and normal contralateral lung, respectively. This indicates significant overcorrection for attenuation when the conventional value of 0.12 cm-1 is used. A value in the range 0.08-0.09 cm-1 would be more appropriate for SPET studies of the thorax. An alternative approach to quantitative region of interest (ROI) analysis is to perform attenuation correction appropriate to the centre of each ROI (using topographical information derived from CT or MRI) on non-attenuation-corrected reconstructions.

Breast Neoplasms

The treatment of resistant neuroblastoma with 131I-mIBG: alternative methods of dose prescription.

A UK multi-centre study has been carried out to collect medical and dosimetry data from treatments with 131I-metaiodobenzylguanidine (mIBG) for patients suffering from resistant neuroblastoma. All data have been acquired in a standardised way, following strict physics and clinical protocols. The accuracy of three different methods of dose prescription was studied. The results show that the most accurate method involved the use of an initial tracer study to determine the therapeutic activity required to deliver a predetermined absorbed whole-body (WB) dose.

3-Iodobenzylguanidine

Monte Carlo modelling of the performance of a rotating slit-collimator for improved planar gamma-camera imaging.

Planar imaging with a gamma camera is currently limited by the performance of the collimator. Spatial resolution and sensitivity trade off against each other; it is not possible with conventional parallel-hole collimation to have high geometric sensitivity and at the same time excellent spatial resolution unless field-of-view is sacrificed by using fan- or cone-beam collimators. We propose a rotating slit-collimator which collects one-dimensional projections from which the planar image may be reconstructed by the theory of computed tomography. The performance of such a collimator is modelled by Monte Carlo methods and images are reconstructed by a convolution and backprojection technique. The performance is compared with that of a conventional parallel-hole collimator and it is shown that higher spatial resolution with increased sensitivity is possible with the slit-collimator. For a point source a spatial resolution of some 6 mm at a distance of 100 mm from the collimator with a x7 sensitivity compared with a parallel-hole collimator was achieved. Applications to bone scintigraphy are modelled and an improved performance in hot-spot imaging is demonstrated. The expected performance in cold-spot imaging is analytically investigated. The slit-collimator is not expected to improve cold-spot imaging. Practical design considerations are discussed.

Equipment Design

Phase I/II study of iodine 131 metaiodobenzylguanidine in chemoresistant neuroblastoma: a United Kingdom Children's Cancer Study Group investigation.

PURPOSE: The goal of this study was to evaluate the toxicity of iodine 131 metaiodobenzylguanidine (mIBG) in metastatic neuroblastoma. PATIENTS AND METHODS: A multicenter phase I study of 131I mIBG has been undertaken by the United Kingdom Children's Cancer Study Group (UKCCSG) in children with advanced chemoresistant neuroblastoma. Activity prescription was based on a prescribed whole-body radiation dose, which was established for individual patients by performing an initial tracer investigation with 75 MBq of 131I mIBG. An activity was derived from this pharmacokinetic study that would deliver an initial whole-body-absorbed radiation dose of 1 Gy. Subsequent dose escalations were based on observed toxicity. RESULTS: Twenty-five patients, aged 1 to 10 years, were treated with prescribed whole-body dose levels of 1.0 Gy (n = 2), 2.0 Gy (n = 13), and 2.5 Gy (n = 10). This necessitated administration of 2.4 to 12.1 GBq of activity. Hematologic, hepatic, kidney, and adrenal toxicity were observed, with bone marrow suppression being the principal dose-limiting toxicity. Bone marrow toxicity increased with prescribed whole-body-absorbed radiation dose, with 80% of patients developing grade 3 or 4 thrombocytopenia at a prescribed whole-body radiation dose of 2.5 Gy. Objective evidence of tumor response was seen in soft tissue (primary or nodal disease), bone, and bone marrow, with an overall response rate of 33% (partial response, n = 8; static disease, n = 9; progressive disease, n = 7). CONCLUSIONS: This study has established an effective method of activity prescription that predicts subsequent toxicity, with the maximally tolerated dose being sufficient activity to deliver a whole-body-absorbed radiation dose of 2.5 Gy. The objective response rate is comparable to other single agents in chemoresistant neuroblastoma and suggests that 131I mIBG may be a useful method for targeting radiotherapy in metastatic neuroblastoma.

3-Iodobenzylguanidine

Treatment planning for 131I-mIBG radiotherapy of neural crest tumours using 124I-mIBG positron emission tomography.

Patients designated to receive 131I-meta-iodobenzylguanadine (mIBG) for the treatment of neural crest tumours have been scanned with 124I-mIBG using the MUP-PET positron camera. Uptake was detected in tumour sites in lung, liver and abdomen. The tomographic images produced have allowed estimates to be made of the concentration of mIBG in both tumour and normal tissue. From these data it is possible to predict the radiation doses that would be achieved using therapy levels (up to 11 GBq) of 131I-mIBG. The levels of tumour uptake are between 0.5 and 2.0 kBq/g indicating that the radiation doses to tumour would be in the range 3 Gy to 7.5 Gy.

3-Iodobenzylguanidine

Dosimetry of iodine 131 metaiodobenzylguanidine for treatment of resistant neuroblastoma: results of a UK study.

In 1987, the United Kingdom Children's Cancer Study Group (UKCCSG) set up a multi-centre study to investigate the toxicity of iodine 131 metaiodobenzylguanidine (mIBG) in the treatment of resistant neuroblastoma. Since December 1987, 25 children suffering from neuroblastoma have been treated with 131I-mIBG at six UK centres. All centres followed standardised physics and clinical protocols to provide consistent toxicity and dosimetry data. These protocols describe the methods employed for both the tracer study using 131I-mIBG and the subsequent therapy. Whole-body dosimetry calculations were performed on data from the tracer study. The activity administered for therapy was the amount predicted to deliver a predefined whole-body dose. Estimates of doses delivered to various organs during treatment are given in Table 1.

3-Iodobenzylguanidine

Measurements of blood-brain barrier permeability in patients undergoing radiotherapy and chemotherapy for primary cerebral lymphoma.

Positron emission tomography (PET) has been used to measure changes in regional blood-brain barrier (BBB) permeability in patients with primary cerebral lymphoma undergoing radiotherapy and chemotherapy. The method employed is to measure the rate of wash-out of a radioactive tracer (68Ga-EDTA) from blood into brain tissue using time-sequence PET imaging. Preliminary studies carried out on patients with more common primary cerebral tumours show that time-activity data are reproducible to approximately 10%. Measurements made in 2 patients with primary cerebral lymphoma treated with initial chemotherapy showed significant changes in permeability in the region of the tumour. Within 5 weeks of the start of treatment, permeability values reached the levels of normal brain. No changes in BBB permeability in normal brain were seen immediately after radiotherapy.

Adult

An evaluation of 99mTc-HMPAO uptake in cerebral gliomas--a comparison with X-ray CT.

Nineteen patients with biopsy-proven cerebral gliomas were studied with 99mTc-HMPAO single photon emission tomography (SPECT) imaging and X-ray computed tomography (CT). The uptake of 99mTc-HMPAO was correlated with tumour size and morphology as shown by X-ray CT, and overall patient survival. It appears that uptake of 99mTc-HMPAO is associated with larger, ill-defined tumours and was an adverse factor in patient survival. In those tumours with normal or increased uptake, 99mTc-HMPAO imaging is useful in distinguishing the tumour margin from surrounding oedema.

Brain Neoplasms

The effects of single dose oral hydralazine on blood flow through human lung tumours.

Hydralazine has been shown to reduce tumour blood flow and to potentiate the cytotoxicity of melphalan and bioreductive agents in mice. In order to determine whether such a strategy might have clinical potential, a study was undertaken to investigate the effects of hydralazine on blood flow through human tumours. Twenty-two patients with carcinoma of the bronchus received a single oral dose of hydralazine in the range 25 to 150 mg (0.37-2.86 mg/kg) according to age and acetylator status. Tumour blood flow was assessed by single photon emission computed tomography (SPECT) performed 10 min following intravenous 99Tcm-HMPAO on two occasions 2-8 days apart, the second being performed 60 min after hydralazine administration. In 20 evaluable patients, hydralazine caused a 38% increase in blood flow through the whole tumour (p = 0.007) and a 28% increase in flow through the tumour centre (p = 0.03) with greater increases occurring in patients sustaining greater falls in peripheral resistance. Tumour vascular resistance fell indicating active vasodilation in arterioles supplying tumours. Side-effects due to hydralazine were reported by eight patients.

Administration, Oral

Thyroid imaging using positron emission tomography--a comparison with ultrasound imaging and conventional scintigraphy in thyrotoxicosis.

Forty-six comparative studies were performed on 41 patients with hyperthyroidism. Clinically these comprised two groups: those with Graves' disease, and those with multinodular goitre. All patients underwent an ultrasound examination and positron emission tomography (PET) using 124I, then gamma camera pinhole imaging following their 131I therapy administration. Although the 131I pinhole imaging was not performed for diagnostic purposes, there was good correlation (78% agreement) between it and 124I PET in determining relative lobe size. Hence either imaging modality could be used as an indicator of the relative radiation dose delivered to each thyroid lobe at a macroscopic level. In terms of gland morphology the PET images corresponded well to the high resolution ultrasound images (78% agreement), unlike the pinhole images which correlated poorly (only 28% agreement). The results showed that PET imaging gives better anatomical and physiological detail than 131I pinhole imaging. In 77% of cases where the pinhole image showed a uniform distribution of radioisotope, the improved spatial resolution of the PET images revealed non-homogeneous distribution indicating a non-uniform distribution of radiation dose. Since all dosimetry calculations are based on the assumption of uniform distribution of radioiodine, this non-uniformity could possibly have important consequences in the outcome of radioiodine therapy in thyrotoxicosis.

Adult

Image quantification with a large area multiwire proportional chamber positron camera (MUP-PET).

A large area multi wire proportional chamber positron camera system is under evaluation for clinical Nuclear Medicine investigation using isotopes both from the house generators (68Ga) and from remote cyclotrons (18F, 124I, 64Cu and 81Rb). Images are reconstructed using a fully three dimensional (3D) algorithm and exhibit equal resolution in all three orthogonal directions. The axial field of view of 15 cm is large enough to allow coverage of the whole brain. This paper discusses the performance of the MUP-PET system with particular emphasis on quantification and the development of an attenuation correction scheme for a large area detector system. The distribution of scattered and accidental events is investigated and observed to contribute a fairly uniform background to the image. Dead time correction factors are calculated from an analytical expression obtained by considering the various sources of dead time present in the system. Following correction for attenuation, accidentals, scattered events and dead time, reconstructed phantom images show a strong linear correlation (r = 0.998) between count density and regional isotope concentration. The extension of the methods to clinical studies is discussed.

Image Processing, Computer-Assisted

Radiation dose assessments in radioiodine (131I) therapy. 1. The necessity for in vivo quantitation and dosimetry in the treatment of carcinoma of the thyroid.

In order to destroy thyroid cancer metastases by radioiodine an average tissue dose of 80-300 Gy is needed. Such high doses can be expected, following the administration of the conventional 5.5 GBq of 131I, only if both the percentage uptake per gram in the target tissue and the effective half life of the radioiodine in it are higher than well-defined threshold values, and if every dimension of the tissue exceeds several millimeters. The fulfillment of such favourable conditions in actual clinical cases can only be confirmed by in vivo quantitation of the absorbed dose achieved as a result of the administration of radioiodine.

Carcinoma

Radiation dose assessment in radioiodine therapy. 2. Practical implementation using quantitative scanning and PET, with initial results on thyroid carcinoma.

We have designed special high-resolution, low-sensitivity collimators for a dual-headed whole-body scanner for imaging and quantifying therapy levels of iodine-131. In addition, we have used positron emission tomography (PET) with a low-cost large-area PET camera to achieve improved accuracy in the estimate to tumor mass. The physical performance of these two imaging systems is described. In order to illustrate the practical implementation of these systems for the assessment of radiation dose to normal and tumour tissue during radioiodine therapy, three clinical examples are reported, and a summary of the initial clinical results obtained from 16 patients with carcinoma of the thyroid is presented. The dose to normal thyroid remnants for patients undergoing ablation ranged from 16 to 400 Gy, while the dose to involved neck nodes ranged from 2.5 to 33 Gy for patients undergoing post-ablation radioiodine therapy. In one patient with distant metastasis in the spine, a dose of 100 Gy was achieved. The techniques described in this paper can be used to determine if sufficient activity can be accumulated in tumours to provide a therapeutic effect while minimising irradiation of normal tissues by avoiding administrations which do not provide tumouricidal radiation doses.

Carcinoma

Technetium-99m HMPAO and SPECT in the assessment of blood flow in human lung tumours.

In order to assess the blood flow patterns through human lung tumours, 20 patients received 400-750 MBq 99TcmHMPAO intravenously 10 min before single photon emission computed tomography (SPECT). Ratios of uptake in the whole tumour relative to normal lung ranged from 0.35 to 1.53 (mean 1.01) with eight tumours showing less uptake than normal lung and ten showing greater uptake. In one patient the tumour was not distinguishable from surrounding lung and in another a large pleural effusion prevented evaluation. Tumour: lung ratios for central tumour regions ranged from 0 to 1.83 (mean 0.80) with 13 showing lower uptake than normal lung and five showing greater uptake. Duplicate scans were performed in eight patients demonstrating satisfactory reproducibility. This technique provides a simple and reproducible method for the assessment of tumour blood flow.

Adult

The performance of a multiwire proportional chamber positron camera for clinical use.

The Rutherford Appleton Laboratory clinical positron camera consists of two opposed multiwire proportional chambers (MWPCS) mounted on a rotating gantry capable of performing routine nuclear medicine studies. The system has operated since the end of 1986 with complete reliability. It has a sensitivity of 37 kcps MBq-1 cm3 per axial cm for a 20 cm diameter uniformly filled cylinder of activity. The best spatial resolution obtainable is about 6 mm, although in practice images are smoothed in order to reduce statistical noise with a corresponding decrease in resolution. Cross-plane rays are utilised during image reconstruction and the resulting three-dimensional images exhibit the same spatial resolution in three orthogonal directions over a large cylindrical field of view 15 cm high by 30 cm in diameter. The maximum data-taking rate is limited to 1.5 to 2 kcps at present due to deadtime in the read-out system. The performance of the system is described with particular reference to the problems of imaging with the large fractions of random and scattered events which are a consequence of using large-area detectors. Images of phantoms and patients are presented and proposed modifications to the camera are described.

Algorithms

Initial experience with Tc-99m-HM-PAO in the study of brain tumors.

A preliminary study of the distribution of the 99mTc complex of hexamethylpropylene amine oxime (HM-PAO) in 12 patients with brain neoplasms before, during, and after radiotherapy has been performed. Untreated brain tumors were found to exhibit a range of 99mTc-HM-PAO uptake, varying from areas of markedly increased isotope activity to photopenic areas, when compared to normal brain tissue. A ratio of 99mTc-HM-PAO tumor uptake to contralateral normal tissue uptake was calculated prior to and during radiotherapy. This ratio tended to return towards unity in lesions responding to therapy. A predictable alteration in whole brain 99mTc-HM-PAO uptake during radiotherapy was not demonstrated. Unlike the radiolabeled amines, 99mTc-HM-PAO localizes in primary tumors, probably indicating that its uptake mechanism is independent of non specific amine receptors. 99mTc-HM-PAO may be useful in the study of brain tumor physiology and response to therapy.

Adult

A simple method of producing parenchymal renograms using parametric imaging.

Standard dynamic renography procedures are used to produce time-activity curves for defined regions of interest around the kidneys. Further analysis of the acquired data using Fitted Retention and Excretion Equations (FREE) to determine single kidney glomerular filtration rate (GFR) and kidney transit time is performed at the Royal Marsden Hospital, Sutton. The disadvantage of these methods is that the renal function is assessed for the whole kidney and not on a regional basis. The aim of this study was to use parametric imaging to extend the standard analysis so that the parenchyma could be identified and analysed separately from the collecting system. The parenchyma pixel time-activity curves have shorter time-to-peak (TTP) values than the collecting system. TTP parametric images were used to set limits on the TTP values and thus define the parenchyma pixels. The time-activity curves from the parenchyma were further analysed using FREE to produce parametric images of both GFR and effective blood volume. Finally, the original dynamic data were re-analysed so that time-activity and FREE curves were generated for the parenchyma alone. A study of 15 patients (30 kidneys) showed that the extended analysis indicated parenchymal isotope clearance. By comparing the time-activity and FREE curves of the whole kidney with those from the parenchyma alone, a more useful analysis of parenchymal function was obtained. This proved to be particularly useful for patients with pelvi-ureteric junction (PUJ) obstruction.

Humans