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D W Townsend

Publications and source records attributed to D W Townsend.

At least 37 records · Page 2Linked to original sources

Minimally invasive surgical biopsy confirms PET findings in esophageal cancer.

This report describes our initial experience using positron emission tomography (PET) scanning in esophageal cancer patients. In two patients PET identified distant metastatic disease missed by conventional staging. Laparoscopic biopsy provided histological confirmation of metastases. In the third patient, locoregional lymph nodes were identified by PET and confirmed by surgical staging. In this preliminary report, PET appears to be a promising new noninvasive modality for staging patients with esophageal cancer.

Adenocarcinoma↗

Role of positron emission tomography in staging esophageal cancer.

BACKGROUND: Conventional noninvasive staging of esophageal cancer is inaccurate. This study investigated the role of positron emission tomography (PET) in staging esophageal cancer. METHODS: Patients with potentially resectable esophageal cancer were included. A whole-body PET scan was acquired after injection of 18F-fluorodeoxyglucose and was evaluated for areas of increased focal uptake. Accuracy was determined by comparing PET with surgical staging. RESULTS: Potentially resectable esophageal cancer was identified in 35 patients. Positron emission tomography detected nine sites of distant metastases missed by conventional scanning, but one false-negative PET scan occurred in a patient with a 2-mm liver lesion. There were 11 false-negative PET scans for small, intracapsular local-regional nodal metastases (mean diameter 5.2 mm; range 2 to 10 mm). For distant metastases, the sensitivity was 88%, the specificity was 93%, and the accuracy was 91%. For local-regional nodal metastases, the sensitivity was 45%, the specificity was 100%, and the accuracy was 48%. CONCLUSIONS: Positron emission tomography improved our ability to detect distant metastases missed by conventional noninvasive staging of esophageal cancer. Small local-regional nodal metastases are not identified by current PET technology. Early use of PET in the staging of patients with esophageal cancer could facilitate treatment planning and identifying unsuspected distant metastases in up to 20% of patients with a negative metastatic survey by conventional staging.

Adenocarcinoma↗

Exact and approximate rebinning algorithms for 3-D PET data.

This paper presents two new rebinning algorithms for the reconstruction of three-dimensional (3-D) positron emission tomography (PET) data. A rebinning algorithm is one that first sorts the 3-D data into an ordinary two-dimensional (2-D) data set containing one sinogram for each transaxial slice to be reconstructed; the 3-D image is then recovered by applying to each slice a 2-D reconstruction method such as filtered-backprojection. This approach allows a significant speedup of 3-D reconstruction, which is particularly useful for applications involving dynamic acquisitions or whole-body imaging. The first new algorithm is obtained by discretizing an exact analytical inversion formula. The second algorithm, called the Fourier rebinning algorithm (FORE), is approximate but allows an efficient implementation based on taking 2-D Fourier transforms of the data. This second algorithm was implemented and applied to data acquired with the new generation of PET systems and also to simulated data for a scanner with an 18 degrees axial aperture. The reconstructed images were compared to those obtained with the 3-D reprojection algorithm (3DRP) which is the standard "exact" 3-D filtered-backprojection method. Results demonstrate that FORE provides a reliable alternative to 3DRP, while at the same time achieving an order of magnitude reduction in processing time.

Algorithms↗

Growth dynamics in a natural biofilm and its impact on oral disease management.

Measurements of the microbial growth dynamics in natural biofilm communities are almost non-existent. In a recent study, the biofilm formation on teeth was examined. A previously unknown active period of bacterial division occurred at a certain density of plaque bacteria on tooth enamel. The density-dependent cell-division phase of plaque formation contributed 90% of the biomass in the first 24 hrs of plaque formation. This suggested that growth was induced by the bacteria. In vitro assays were developed for rapid evaluation of the growth of surface-linked bacteria by the measurement of cellular components associated with growth on a per cell per time basis. Cell-free supernatants (termed START) of media in contact with bacteria were assayed for their effects on DNA synthesis and other cellular components associated with growth. START was found to increase the incorporation of [3H-methyl]-thymidine on a per cell per time basis, when compared with media not in contact with bacteria. Additional in vivo studies and in situ-based models of complex biofilms are needed if all of the mechanisms involved in the rapid accumulation of biofilm bacteria on teeth and other surfaces are to be understood.

Amino Acids↗

A performance study of 3D reconstruction algorithms for positron emission tomography.

This paper investigates the statistical and systematic accuracy of five three-dimensional reconstruction algorithms for multi-ring PET scanners operated without septa: the reprojection method, the direct Fourier reconstruction, the FAVOR algorithm, and the single-slice and multi-slice rebinning algorithms. Simulated data of a uniform cylinder, of Gaussian sources, and of spherical sources are used to compare respectively the noise properties, the modulation transfer function, and the recovery coefficients of the algorithms. Brain scans reconstructed with the different algorithms are compared by calculating the linear regression of the mean values within regions of interest. The most significant observations are a slight loss of transaxial resolution with the reprojection algorithm in the external slices of the scanner, and increased noise in the images reconstructed using multi-slice rebinning.

Algorithms↗

Pure amnesia after unilateral left polar thalamic infarct: topographic and sequential neuropsychological and metabolic (PET) correlations.

A 54-year-old patient who had an isolated small polar thalamic infarct and acute global amnesia with slight frontal type dysfunction but without other neurological dysfunction was studied. Memory improved partially within 8 months. At all stages the impairment was more severe for verbal than non-verbal memory. Autobiographic recollections and newly acquired information tended to be disorganised with respect to temporal order. Procedural memory was unaffected. Both emotional involvement and pleasure in reading were lost. On MRI, the infarct was limited to the left anterior thalamic nuclei and the adjacent mamillothalamic tract. The regional cerebral metabolic rate of glucose (measured with PET) was decreased on the left in the thalamus, amygdala, and posterior cingulate cortex 2 weeks after the infarct, and in the thalamus and posterior cingulate cortex 9 months later. These findings stress the specific role of the left anterior thalamic region in memory and confirm that longlasting amnesia from a thalamic lesion can occur without significant structural damage to the dorsomedial nucleus. Furthermore, they suggest that the anterior thalamic nuclei and possibly their connections with the posterior cingulate cortex play a role in emotional involvement linked to ipsilateral hemispheric functions.

Amnesia↗

A rotating PET scanner using BGO block detectors: design, performance and applications.

Recent advances in fully three-dimensional reconstruction for multi-ring PET scanners have led us to explore the potential of a prototype scanner based on the rotation of two opposing arrays of BGO block detectors. The prototype contains only one-third of the number of detectors in the equivalent full ring scanner, resulting in reduced cost. With a lower energy threshold at 250 keV, the absolute efficiency of the scanner is 0.5% and the scatter fraction is 35% for a 20-cm cylinder. Transaxial and axial spatial resolution is about 6 mm. The maximum noise equivalent count rate estimated for a 15-cm diameter cylinder is 36,000 cps at a concentration of 26 kBq/ml. The minimum scan time for a 18F-fluoro-2-deoxyglucose (FDG) brain study is 55 sec. The camera has been validated for clinical applications using both FDG and 82Rb.

Algorithms↗

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↗

An analysis of air-stepping in normal infant vervet monkeys.

Limb movements during air-stepping were analyzed in three neonatal vervet monkeys over a three-week period. The movements had similar temporal organization both across animals and across time. For example, the duration of both the hind and the forelimb cycle equaled about 500 ms, with hind limb return strokes lasting much longer than the hind limb power strokes. Furthermore, there were clear indications of both intra- and interlimb coordination. Specifically, all the joints of a limb tended to flex and extend simultaneously, and contralateral and ipsilateral limb pairs had an average phase relationship of approximately 50% of cycle duration. Despite a qualitative similarity between limb movements during air-stepping in the neonates and overground locomotion in older animals, there were notable differences both in temporal relationships and joint displacement patterns. Finally, there appeared to be important similarities between air-stepping in these monkeys and stepping in newborn humans. Most notably, both tended to disappear after a limited period. The implications of these similarities, as well as the overall results, are discussed in relation to the understanding of the development of locomotor behavior in human and nonhuman primates, using approaches based both upon the hard-wired and dynamic models.

Journal Article↗

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↗