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D W Townsend

Publications and source records attributed to D W Townsend.

15 recordsLinked to original sources

Physical performance of a positron tomograph for brain imaging with retractable septa.

Performance characteristics of a new design of positron tomograph with automatically retractable septa for brain imaging have been studied. The device, consisting of block BGO detectors (8 x 8 elements per block), has a ring diameter of 76 cm and an axial FOV of 106.5 mm. The in-plane resolution is on average 5.8 mm and 5.0 mm (FWHM) for stationary and wobble sampling, respectively, over the central 18 cm of the transaxial FOV. Its unique feature is the capability of data acquisition both in the 'conventional' 2D mode (with septa) or 3D mode (septa retracted) where coincidences between any of the 16 detector rings are acquired. When scattered events are subtracted, the efficiency for a 20 cm diameter uniform cylinder increases overall by a factor of 4.8 between 2D (septa extended) and 3D modes. For a 20 cm phantom the trues/singles ratio is higher for 3D than for 2D but for a given unscattered trues rate, the randoms rate in 3D is higher. At 380 keV the scatter fraction within a 20 cm cylinder is 10% (septa extended) and 36% (retracted). In spite of the increase in scatter when septa are retracted, the increased efficiency in the 3D mode of acquisition yields distinct advantages, particularly in the many studies where tracer concentration is low and consequently where dead time and random rates are less important.

Brain

Alkaline phosphatase activity and pyridoxal phosphate concentrations in the milk of various species.

Because pyridoxal phosphate does not normally cross membranes, it was intriguing that the concentration of pyridoxal phosphate is much higher in goat milk than in human milk. We also noted that, although the total vitamin B-6 concentration of bovine milk was similar to that of caprine milk, the bovine milk had lower pyridoxal phosphate. Preliminary data from five Alpine goats, five Brown Swiss cows, five Holstein cows and three humans suggested that there was an inverse relationship between pyridoxal phosphate concentration and phosphatase activity in the goats and cows but not in the humans. This was confirmed with additional data from Nubian goats, Jersey and Guernsey cows, and crossbred sows. Combining the animal data yielded the following relationship between pyridoxal phosphate (PLP, mumol/L) and alkaline phosphatase (P'ase) activity (mmol/(min.L): PLP = 2.03e(-2.26 P'ase) + 0.03. The human milk samples were low in both pyridoxal phosphate and alkaline phosphatase. We conclude that in goats, cows and pigs a significant fraction of the vitamin B-6 appearing in the milk is secreted as pyridoxal phosphate, probably bound to protein, and varying amounts may then be hydrolyzed back to pyridoxal depending on the alkaline phosphatase activity. Human mammary tissue apparently secretes very little pyridoxal phosphate.

Alkaline Phosphatase

Metabolism of [14C]- and [32P]pyridoxal 5'-phosphate and [3H]pyridoxal administered intravenously to pigs and goats.

To gain more information about the kinetics of vitamin B-6 metabolism in vivo, the metabolism of tracer was examined after the simultaneous intravenous administration of [32P] and [14C]pyridoxal phosphate and [3H]pyridoxal in two 93-kg pigs and two 60-kg goats. In the pigs, [14C] removal was monophasic with T1/2 of 16 and 18 min and clearance of 165 and 248 mL/min. In the goats, [14C] removal was biphasic with T1/2 of 49 and 114 min for 0-30 min and 209 and 227 min for 0.5-6 h (clearance 20 and 17 mL/min). Uptake of pyridoxal phosphate by liver and resecretion into the plasma were too small to cause a detectable decrease in the [32P]:[14C] ratio. Pyridoxal removal from plasma was similar in both species, with a half-life of approximately 12 min from 0-30 min and approximately 50 min for 0.5-3 h. Clearance of [3H]pyridoxal in the four animals ranged from 412 to 2258 mL/min. Little [14C] entered the erythrocytes. The [3H] entered readily but was converted to pyridoxal phosphate faster in the pigs than in the goats. [14C] and [3H] were excreted as pyridoxic acid at the same rate. However, during the 54 h after injection the goats excreted approximately 60% of the [14C] doses in the urine compared with approximately 30% in the pigs. About 5-10% of the [14C] and [3H] doses were recovered in goat milk over 54 h. Pyridoxal kinase activity was higher in lactating mammary tissue than in liver, kidney or muscle of goats.

Animals

Optimization of signal in positron emission tomography scans: present and future developments.

The absolute sensitivity of a state-of-the-art, commercial neuroPET tomograph with interplane septa is about 0.5%. This poor utilization of the available photons could be improved by increasing the intrinsic efficiency of the detection process and, more significantly, by increasing the solid angle coverage of the tomography. While multi-ring scanners currently have an axial length of about 10 cm, the useful solid angle is limited by the presence of interplane septa. These septa reduce the acceptance rate not only of scattered photons but also of true unscattered coincidences, although in studies performed at high photon counting rates the loss of potential signal may be less important than a reduction in scatter. Removal of the septa increases the absolute sensitivity of the scanner to about 3%, a figure which also includes an unavoidable increase in scattered photons. However, in studies performed at low photon counting rates, any increase in scattered and random (uncorrelated) coincidences resulting from septa removal may be an acceptable price to pay for the accompanying increase in signal, provided that there is a real improvement in the signal-to-noise ratio. Recently, scanners with automatically retractable septa have become commercially available, thus enabling the configuration (i.e. septa extended or retracted) to be selected according to the study to be performed.

Algorithms

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

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

Effects of size on vervet (Cercopithecus aethiops) gait parameters: a longitudinal approach.

Changes in the values of certain locomotor parameters were analyzed over a range of speeds for five immature vervet monkeys sampled at 6 month intervals over approximately a 3 year period. Lateral and diagonal sequence walking gaits and transverse and rotary gallops were commonly used. The monkeys switched from walking to galloping at long cycle durations for their mass, although, as a group, their transition speeds were in agreement with data from other mammals. However, for individual monkeys, transition speed was not consistently dependent on body mass. Cycle and stance durations generally increased with increasing size at each speed for each animal, with the greatest increases occurring at slower speeds. Swing durations increased slightly with size. For any particular individual, speed was highly predictable from cycle (or stance) duration and body mass (or age). However, the multiple regression equations for each animal were significantly different from each other, suggesting that no single equation is satisfactory for all of the individuals within a species.

Aging

Three-dimensional image reconstruction from complete projections.

Three-dimensional medical image reconstruction for both transmission and emission tomography has traditionally decomposed the problem into a set of two-dimensional reconstructions on parallel transverse sections. There is, however, increasing interest in reconstructing projection data directly in three dimensions. For emission tomography in particular, such a reconstruction procedure would clearly make more efficient use of the available photon flux. In the past few years, a number of authors have studied the problems associated with full three-dimensional reconstruction, especially in the case of positron tomography where three-dimensional reconstruction is likely to offer the greatest benefits. While most approaches follow that of filtered backprojection, the relationship between the various filters that have been proposed is far from evident. This paper clarifies this relationship by analysing and generalising the different classes of published filters and establishes the properties and characteristics of a general solution to the three-dimensional reconstruction problem. Some guidelines are suggested for the choice of an appropriate filter in a given situation.

Algorithms

Role of intestinal microflora in the metabolism of vitamin B-6 and 4'-deoxypyridoxine examined using germfree guinea pigs and rats.

In previous work identification of urinary metabolites of 4'-deoxypyridoxine which had been oxidized in the 5'-position and long-term dilution of labeled urinary metabolites with unlabeled molecules suggested possible microbial contributions. In the current studies germfree guinea pigs were able to convert 4'-deoxypyridoxine to 4'-deoxy-5-pyridoxic acid demonstrating that the ability to oxidize the 5'-position is not restricted to microorganisms. Labelling curves for urinary pyridoxic acid in rats continuously fed [14C]pyridoxine since weaning were similar in conventional and germfree animals indicating that any vitamin B-6 synthesized in the intestinal tract was not readily absorbed and metabolized. Therefore, coprophagy did not make a detectable contribution to vitamin B-6 metabolism in rats receiving a nutritionally complete diet. The difficulty in achieving comparable labeling in adult animals is probably due to very slow turnover of portions of the vitamin B-6 pool and not to microbial production of vitamin B-6. The total pool calculated from the radioactivity in the germ-free rats averaged 16.2 +/- 0.8 nmol vitamin B-6 compounds/g body wt. Only 10% of the ingested label was recovered in the feces. In addition, only about 50% of the label excreted in the urine appeared as 4-pyridoxic acid in rats. These observations suggest that it may be difficult to quantitate the total urinary and fecal excretion of ingested vitamin B-6 without using tracers.

Animals

A multicompartment model of vitamin B6 metabolism.

The shape of the labelling curve for urinary pyridoxic acid following a single dose of labelled pyridoxine can be most easily described by a two compartment model. However, the usefulness of such a model is limited because the two pools have no physiological identity; the model does not describe the many metabolic interconversions associated with vitamin B6 metabolism; and the predictions of the total size of the vitamin B6 pool are not consistent with data from direct measurements. Therefore, we have been using the Simulation, Analysis, and Modelling program (SAAM) developed at the National Cancer Institute to develop an improved model. Since the SAAM 29 program is limited to 25 pools, only a few of the many tissue vitamin B6 pools could be included. Muscle and liver were chosen because they contain 80 to 90% of the vitamin B6 in the body. Plasma and erythrocytes were selected because of their importance in transport. This review traces the development of the model to its current stage and shows comparisons between the predictions of the model and a variety of data from the literature. At this point the emphasis has been on describing metabolism in rats because the most detailed kinetic data available were obtained from rats. The predictions of the current model do not match all available observations. However, the results are sufficiently encouraging to warrant continued development.

Animals

Plasma catecholamines associated with hypothalamically-elicited defense behavior.

Sympatho-adrenal (SA) activation was determined by measuring levels of norepinephrine (NE) and epinephrine (E) in bilateral adrenal venous and peripheral venous plasma of 20 anesthetized cats following stimulation of medial hypothalamic sites. Hypothalamic sites were selected that elicited affective defense behavior in the freely moving cat. Fifty-eight percent of these hypothalamic sites elicited a bilateral increase greater than or equal to 10 ng/min in the output of both adrenal catecholamines (CAs); these increases were greater from the gland ipsilateral to the side of stimulation. Other SA responses included both preferential increases or decreases in either NE or E. Under baseline conditions, an average of 67% of the NE in the peripheral venous plasma was contributed by the sympathetic noradrenergic nerves; hypothalamic stimulation at "defense" sites increased the contribution to 75%. The data suggest that hypothalamic regions that elicit defense behaviour may overlap with regions that activate the adrenal medullary and sympathetic nervous systems.

Adrenal Medulla

Increases in blood flow from the adrenal gland following medial hypothalamic stimulation in the cat.

Medial hypothalamic sites previously shown to elicit either flight or defense were stimulated in the anesthetized cat. The rate of blood flow from the adrenolumbar (AL) vein ipsilateral to the side of stimulation was measured, as well as the adrenal output of norepinephrine and epinephrine (E). Stimulation at nearly 15% of the hypothalamic sites increased ipsilateral AL venous flow more than 20% over baseline rates. These sites also significantly increased heart rate, mean arterial pressure, and output of E from the ipsilateral adrenal gland. These observations suggest that hypothalamic sites where stimulation increased AL venous flow may overlap with regions that selectively mediate the release of E from the adrenal medulla.

Adrenal Glands

Dopa oxidase activity in human hair bulbs measured by high-performance liquid chromatography.

A method for measuring the dopa oxidase (DO) activity of human hair bulb tyrosinase has been developed and the results of this method have been compared with the tyrosine hydroxylase (TH) activity of hair bulb tyrosinase for brown-, black-, blond-, and red-haired subjects. The method takes advantage of the rapid trapping of dopaquinone by cysteine with the subsequent formation of cysteinyldopas which can be measured by high-performance liquid chromatography. 5-S-Cysteinyldopa (5SCD) and 2-S-cysteinyldopa (2SCD) were detected in the reaction products. Formation of 5SCD correlated with the TH activity over the full range of hair colors and enzyme activity, while 2SCD appeared to be formed nonenzymatically. The absolute amount of 2SCD was constant for each individual but did not correlate with hair color or TH activity. The formation of 5SCD was linear for 60 min while most of the 2SCD was formed within seconds and did not change with time. White hair bulbs which demonstrated no TH activity formed 2SCD, but not 5SCD. We conclude that tyrosinase activity can be quantitated in human hair bulbs by this method, and that TH and DO are coordinate functions of tyrosinase over a broad range of hair color and enzyme activity.

Catechol Oxidase

Modelling vitamin B6 metabolism in rodents (review).

Several improvements have been incorporated into a previously described compartmental model of vitamin B6 metabolism in order to expand the application of the model to non-steady state conditions such as growing animals and differing vitamin B6 intakes. A function which describes the growth of rats receiving various vitamin B6 intakes has been developed. The turnover rates for enzymatic reactions have been written in a form which responds to changes in substrate concentration. The predictions of the model are in reasonable agreement with several sets of data from the literature. Further refinement of the model is in progress.

Animals