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T Jones

Publications and source records attributed to T Jones.

At least 325 records · Page 18Linked to original sources
PubMed1991

A normalization technique for 3D PET data.

Prior to reconstruction, emission data from a multi-ring PET camera must be corrected (normalized) for variations in detector sensitivity. The appropriate correction coefficients are obtained by measuring the response of all coincidence lines to a calibrated source of activity (a blank scan). State-of-the-art cameras may contain up to a million such lines of response (LORs), and therefore around 400 million counts will be required to calibrate each LOR to a statistical accuracy of 5%. Alternatively, by modelling the LOR sensitivity as the product of the individual detector efficiencies and a geometrical factor, a calibration procedure has been proposed which requires the determination of only 6000 parameters from this same data set. A significant improvement in the statistical accuracy of the coefficients can therefore be expected. Recently, multi-ring scanners have been operated with the septa retracted, increasing the number of measured LORs by a factor of eight. The acquisition of the calibration data necessary to achieve adequate statistical accuracy then becomes prohibitive. We show that, by modelling the LOR sensitivity, it is possible, with certain approximations, to normalize a septa-retracted emission data set with good accuracy. The input to the model is a high statistics blank scan acquired with the septa extended, which offers a number of practical advantages.

Calibration↗
PubMed1991

Diffuse-adhering Escherichia coli (DAEC) as a putative cause of diarrhea in Mayan children in Mexico.

Diarrhea is a major cause of infantile morbidity and mortality in developing countries. A community-based, case control study was conducted in a southern Mexican Mayan village for 3 weeks during the peak diarrhea period to prospectively identify the infectious agents associated with childhood diarrheal disease. Several enteropathogens were isolated from stools of 34 of 58 cases, although none was significantly associated with diarrhea. For the 24 cases from which no enteropathogens were isolated, diffuse-adhering Escherichia coli (DAEC) strains were significantly associated with diarrheal disease (P less than .02; odds ratio = 6; 95% confidence limit, 1.08-99.0). DAEC were highly heterogeneous with respect to plasmid content and serotype. Three DNA probes designed to differentiate E. coli exhibiting localized, diffuse, or aggregative adherence were compared with results from a standard HeLa cell binding assay to assess the utility of these probes in the field. This study provides evidence for the potential pathogenic capacity of DAEC and underscores the variety of diarrheal agents operating within a community.

Bacterial Adhesion↗
PubMed1991

A method of studying pharmacokinetics in man at picomolar drug concentrations.

1. We describe a new method that enables the tissue kinetics of picomolar concentrations of drugs to be measured in man. The method is based on the administration of a drug, labelled with a short-lived positron-emitting radioisotope, such as carbon-11 (t1/2 = 20.4 min, beta + = 99.8%) or fluorine-18 (t1/2 = 109.8 min, beta + = 96.9%), which is then detected in vivo by an array of 10 large uncollimated sodium iodide scintillation detectors, arranged as five opposing pairs, with each pair collecting data over one major organ or region of the body. 2. To illustrate the scope of the new method we report the results of administering [O-methyl-11C]-diprenorphine, an established radioligand for central opiate (mu, kappa, and delta) receptors and L-6-[18F]-fluoro-DOPA, a marker for dopaminergic neurons. 3. Only 2-10 muCi (74-370 kBq) of radioactivity are used and, as a consequence of the high specific activities with which carbon-11 and fluorine-18 labelled compounds can be prepared, the method requires less than a nanomole of drug to be administered. In many cases, this amount of drug might be considered low enough to avoid any adverse biological effect. Furthermore repeat studies are possible in many without delivering unacceptable radiation burdens. 4. The high sensitivity realised for both radioactivity and mass suggests a mean for determining the human biodistribution of a new drug at a very early stage in its development. This has potential benefit to drug discovery programmes and to ensuing drug therapies.

Blood-Brain Barrier↗
PubMed1991

Opiate blockade enhances hypoglycemic counterregulation in normal and insulin-dependent diabetic subjects.

To examine the impact of opiate blockade on glucose counterregulation we performed two hypoglycemic insulin clamp studies with and without naloxone in healthy subjects and well-controlled insulin-dependent (IDDM) patients with defective glucose counterregulation. During both studies plasma glucose fell to 55-60 mg/dl and was then maintained at that level using a variable glucose infusion. In normal subjects, naloxone increased glucose production, thereby reducing the exogenous glucose dose needed to maintain the hypoglycemic plateau. Epinephrine and cortisol responses to hypoglycemia were increased during naloxone plus insulin compared with insulin alone; glucagon responses were unaffected. IDDM patients with suppressed hepatic and hormonal responses to insulin-induced hypoglycemia also demonstrated greater stimulation of glucose production as well as epinephrine, growth hormone, and cortisol release during the naloxone study. In the absence of hypoglycemia, naloxone did not significantly affect glucose production or glucoregulatory hormones. We conclude that opiate blockade augments glucoregulatory responses to insulin-induced hypoglycemia, even in IDDM patients with preexisting defects in glucose counterregulation. This effect is at least in part due to enhanced counterregulatory hormone release during hypoglycemia. Endogenous opiates may modulate hormonal responses during hypoglycemia; their blockade could provide a means of ameliorating defective counterregulation in IDDM patients.

Adult↗
PubMed1991

Noninvasive quantification of regional myocardial blood flow in coronary artery disease with oxygen-15-labeled carbon dioxide inhalation and positron emission tomography.

BACKGROUND: Oxygen-15-labeled water is a diffusible, metabolically inert myocardial blood flow tracer with a short half-life (2 minutes) that can be used quantitatively with positron emission tomography (PET). The purpose of this study was to validate a new technique to quantify myocardial blood flow (MBF) in animals and to assess its application in patients. METHODS AND RESULTS: The technique involves the administration of 15O-labeled carbon dioxide (C15O2) and rapid dynamic scanning. Arterial and myocardial time activity curves were fitted to a single tissue compartment tracer kinetic model to estimate MBF in each myocardial region. Validation studies consisted of 52 simultaneous measurements of MBF with PET and gamma-labeled microspheres in nine closed-chest dogs over a flow range of 0.5-6.1 ml/g/min. A good correlation between the two methods was obtained (y = 0.36 + 1.0x, r = 0.91). Human studies consisted of 11 normal volunteers and eight patients with chronic stable angina and single-vessel disease, before and after intravenous dipyridamole infusion. In the normal group, MBF was homogeneous throughout the left ventricle both at rest and after administration of dipyridamole (0.88 +/- 0.08 ml/g/min and 3.52 +/- 1.12 ml/g/min, respectively; p less than or equal to 0.001). In patients, resting MBF was similar in the distribution of the normal and stenotic arteries (1.03 +/- 0.23 and 0.93 +/- 0.21 ml/g/min, respectively). After dipyridamole infusion, MBF in normally perfused areas increased to 2.86 +/- 0.83 ml/g/min, whereas in the regions supplied by stenotic arteries it increased to only 1.32 +/- 0.27 ml/g/min (p less than or equal to 0.001). CONCLUSIONS: PET with C15O2 inhalation provides an accurate noninvasive quantitative method for measuring regional myocardial blood flow in patients.

Animals↗
PubMed1991

Endogenous opiate response to pain in rheumatoid arthritis and cortical and subcortical response to pain in normal volunteers using positron emission tomography.

Identification of the main areas in the brain that respond specifically to the "suffering" components of pain has been achieved by using serial dynamic measurements of blood flow as an index of synaptic activity. Specific response to a repeated painful thermal stimulus as compared to a non-painful thermal stimulus in normal male volunteers identified the anterior cingulate cortex and the thalamus contralateral to the side of stimulation as the main sites of significant response. It was concluded that it was these areas where pain was likely to be experienced. Changes in opioid receptor binding in the brain was measured using 11C-diprenorphine and positron emission tomography in three patients with rheumatoid arthritis. In the two patients with active rheumatoid arthritis substantial changes in opioid receptor binding in the brain are described. The significance of these findings are discussed.

Arthritis, Rheumatoid↗
PubMed1991

Terbinafine levels in serum, stratum corneum, dermis-epidermis (without stratum corneum), hair, sebum and eccrine sweat.

We determined terbinafine levels in serum, stratum corneum, dermis-epidermis (without stratum corneum), hair, sebum and eccrine sweat before, during and after 250 mg doses orally to volunteers once daily. Terbinafine is concentrated rapidly in stratum corneum (up to 9.1 micrograms/g of tissue) primarily by diffusion from the vascular system through the dermisepidermis. It also reaches high concentration in sebum (up to 45.1 micrograms/ml) after several days and continue to concentrate in sebum for up to two days after discontinuation of drug. Hair concentration reach levels of 2.6 micrograms/g of tissue indicating high drug levels in and around the hair follicle. It is not found in sweat. Plasma levels range between 0.1 and 1.0 micrograms/ml. There is a tenfold accumulation of drug in stratum corneum by day 2. Elimination of drug from tissue occurs with a half-life of 4 to 5 days and with the potential for drug levels above fungicidal concentrations for dermatophytes for more than 3 weeks. The tissue pharmacokinetic profile of terbinafine is similar to that of another lipophilic drug, itraconazole, but is very different from ketoconazole and griseofulvin. Higher levels of terbinafine are achieved than of either of the imidazoles and remain longer than griseofulvin.

Adolescent↗
PubMed1991

Implementing a record-oriented clinical lab interface using HL7 version 2.1 at Indiana University Hospital.

At the Indiana University Hospital (IUH) site on the Indianapolis campus, HL7 version 2.1 is being implemented via a TCP/IP LAN, (using the "Minimal" Lower Layer Protocol). HL7 is currently being used to convey record-oriented lab results from the local clinical laboratory system to a clinical database system via an intelligent router, which also provides store and forward capabilities. The database application displays the lab results in a variety of configurable formats to clinical users.

Clinical Laboratory Information Systems↗
PubMed1991

Clinical objectives, tracer constraints and technological requirements for in vivo imaging.

The aim of this paper is to identify future directions for developing instrumentation to measure the tissue kinetics of tracers labelled with positron emitting isotopes. A principal theme developed is the need to realise increased sensitivity for detection. In order to present the case for these improvements, examples are shown of current procedures which would improve with increased sensitivity.

Animals↗
PubMed1991

Normalisation and reconstruction of PET data acquired by a multi-ring camera with septa retracted.

Emission scan data acquired by a multi-ring PET camera operated with septa retracted must be corrected for (1) geometrical and detector sensitivity variations between the different lines of response (normalisation), (2) photon attenuation, and (3) mispositioned events due to photon scattering. These corrections must be applied to the full 3-D set of lines of response before reconstruction. The standard normalisation and attenuation correction procedures for 2-D scans increase the statistical noise in the emission scan, a problem which becomes even more serious in 3-D because of the large number of LORs involved (approximately 8 million). This paper will describe a fully 3-D reconstruction algorithm for multi-angle PET data incorporating a practical normalisation and attenuation correction procedure which minimises the increase in emission scan statistical noise. The correction factors are derived from 2-D, septa extended scans. The algorithm is currently used to reconstruct 3-D emission data from an ECAT 953B, a sixteen-ring PET camera with retractable septa.

Algorithms↗
PubMed1991

The on-line monitoring of continuously withdrawn arterial blood during PET studies using a single BGO/photomultiplier assembly and non-stick tubing.

A robust, highly sensitive system is described for monitoring the concentration of positron emitting radioisotopes contained within arterial blood continuously withdrawn during PET studies of the brain. Utilizing a specially designed flow-through bismuth germanate detector, gammas are more effectively counted, replacing the less efficient method of positron detection with plastic detectors. A polytetrafluoroethylene flow path system has been developed to overcome the problem of highly cohesive tracers adhering to the tubing material. Blood is drawn through the system from the radial artery by a medically approved peristaltic pump. Syringe samples of blood are extracted periodically downstream of the detector, for calibrations, plasma assays, metabolic analysis and physiological measurements. The complete system, including efficient heavy lead shielding is contained on a bedside trolley. Blood activity is continuously recorded throughout the PET investigations, and stored directly by the scanning computer, and additionally backed up on disc by a P.C.

Bismuth↗
PubMed1991

Measurements of regional ventilation pulmonary gas volume: theory and error analysis with special reference to positron emission tomography.

The adaptation to PET of the steady-state technique for the measurement of alveolar ventilation, based on the short-lived radionuclide 19Ne (T1/2 = 17.4 sec), allows the steady-state lung model to be analyzed in a quantitative way under well-defined geometrical conditions. The regional gas volume is essential to this analysis, and regional measurements of the pulmonary gas volume based on transmission tomography are presented and validated in this paper. The accuracy of the steady-state method rests largely with the validity of the lung model applied to describe the transport of tracer in the lung. This study considers tracer transport and mixing within individual lung regions. Blood flow and the alveolar-to-capillary exchange of gases do not significantly affect the values obtained, not even in regions with highly abnormal ventilation/perfusion ratios. A nonuniform intra-regional gas flow distribution results in an underestimation of the regional ventilation, determined by the dispersion of the ventilatory turnover rates of alveolar gas within the region. In the normal lung this underestimation is negligible. In disease, a mixing within the resolution volume of units that are almost non-ventilated and units that perform normally may result in an underestimation of alveolar ventilation by up to 60%.

Humans↗
PubMed1991

Myocardial tissue fraction--correction for partial volume effects and measure of tissue viability.

We have compared two independent methods of correcting the systematic underestimation in measurements of myocardial radiotracer concentration due to wall motion and small transmural wall thickness in cardiac PET studies. The first technique was based on measurement of the tissue fraction by fitting 15O-labeled water dynamic PET data. The other technique involved the subtraction of the C15O-blood volume scan from the transmission data, producing an image of extravascular density. In normal myocardial regions, both values were observed to be about 60% of myocardial tissue density. The tissue fraction was approximately 10% larger than the extravascular density in normal tissue regions. The ratio of alpha/Dev indicates the proportion of the total extravascular tissue for a given ROI that is perfusable by water--independent of the partial volume effect. This ratio was confirmed to be the expected value in normal tissue regions but was reduced in regions of infarction. The use of 15O-water, C15O and transmission data may aid in the differentiation between perfusable and nonperfusable tissue in the infarcted myocardium.

Adult↗