Biomedical subjects
Publications and source records attributed to A Gee.
This paper describes techniques for the visualization and processing of three-dimensional (3D) ultrasound data. The nature of such data demands specialized algorithms, which differ from those employed for other medical imaging modalities. In this paper, the emphasis is placed on generic processing techniques, which are relevant across a wide range of 3D ultrasound application domains.
Shame has been shown to be related both to symptoms of depression and eating pathology. However, the independence of this relationship has not yet been established. The purpose of the present study was to determine whether the relationship between shame and eating disorder symptoms was independent of the relationships of these variables with depression. Seventy non-clinical female participants completed measures of eating disorder-related concerns using the Eating Disorder Examination-Questionnaire version (EDE-Q), depressive symptoms using the Beck Depression Inventory (BDI-II) and two measures of shame, the Other As Shamer Scale (QAS) and the Test of Self-Conscious Affect (TOSCA). Despite a strong association between BDI-II and EDE-Q scores and a moderate relationship between the shame measures, the two measures of shame showed some specificity in their relationships with symptom measures. The OAS was independently related to levels of BDI-II scores while the TOSCA was independently related to scores on the EDE-Q. There are a number of differences between the two measures of shame used in this study. The fact that each was differentially related to eating concerns and depressive symptoms may give clues as to which aspects of shame are important in each of the two types of pathology.
The effect of rolipram, a selective inhibitor of phosphodiesterase type 4 (PDE(4)) and elevating cyclic AMP (cAMP), on in vivo and in vitro (3)H-N-methylpiperidyl benzilate ((3)H-NMPB) binding to muscarinic acetylcholine receptors in the mouse brain was examined. Rolipram significantly decreased in vivo (3)H-NMPB binding in the cerebral cortex, hippocampus and striatum, whereas in vitro (3)H-NMPB binding in these regions was not altered. Saturation experiments on in vivo binding in conjunction with the kinetic analysis revealed that the apparent association rate constant (k(on)) of (3)H-NMPB binding in vivo was significantly decreased by rolipram. A similar decrease in the apparent association rate constant (k(on)) by rolipram was reported for dopamine D(1) and D(2) receptor binding in vivo. These results indicate that rolipram plays an important role in the global modulation of apparent rates of ligand-receptor interactions in the intact brain.
In order to clarify whether changes in brain concentrations of the second messenger cyclic AMP (cAMP) affect in vivo receptor binding in the brain, the effects of rolipram, a selective inhibitor of phosphodiesterase type 4 (PDE(4)), on dopamine receptor binding in the mouse brain were studied. Rolipram significantly decreased in vivo (3)H-SCH 23390 (dopamine D(1) selective radioligand) binding in the mouse striatum in a dose-dependent manner. In vivo saturation experiments together with the kinetic analysis of (3)H-SCH 23390 binding revealed that the apparent association rate constant (k(on)) for (3)H-SCH 23390 binding rather than the maximum number of binding sites available (B(max)) was decreased by rolipram. (3)H-N-methylspiperone (NMSP, dopamine D(2) selective radioligand) binding in the mouse striatum was also decreased by rolipram whereas no significant changes in (3)H-raclopride (dopamine D(2) selective radioligand) binding were observed. As (3)H-raclopride binding has been reported to be much more sensitive than (3)H-NMSP binding to competition by endogenous dopamine, the decreases in (3)H-SCH 23390 and (3)H-NMSP binding cannot be attributed to competitive inhibition by endogenous dopamine. These results indicate that changes in second messenger cAMP concentrations may affect the apparent bimolecular association rate constant (k(on)) of dopamine receptor binding in intact brain. This may be mediated by changes in the receptor micro-environment and altered actual free ligand concentration surrounding the receptors.
The in vivo binding kinetics of 11C-iomazenil were compared with those of 11C-flumazenil binding in rhesus monkey brain. The monkey was anesthetized with ketamine and intravenously injected with either 11C-iomazenil or 11C-flumazenil in combination with the coadministration of different doses of non-radioactive flumazenil (0, 5 and 20 microg/kg). The regional distribution of 11C-iomazenil in the brain was similar to that of 11C-flumazenil, but the sensitivity of 11C-iomazenil binding to competitive inhibition by non-radioactive flumazenil was much less than that of 11C-flumazenil binding. A significant reduction in 11C-flumazenil binding in the cerebral cortex was observed with 20 microg/kg of flumazenil, whereas a relatively smaller inhibition of 11C-iomazenil binding in the same region was observed with the same dose of flumazenil. These results suggest that 11C-flumazenil may be a superior radiotracer for estimating benzodiazepine receptor occupancy in the intact brain.
Freehand 3D ultrasound is particularly appropriate for the measurement of organ volumes. For small organs, which can be fully examined with a single sweep of the ultrasound probe, the results are known to be much more accurate than those using conventional 2D ultrasound. However, large or complex shaped organs are difficult to quantify in this manner because multiple sweeps are required to cover the entire organ. Typically, there are significant registration errors between the various sweeps, which generate artifacts in an interpolated voxel array, making segmentation of the organ very difficult. This paper describes how sequential freehand 3D ultrasound, which does not employ an interpolated voxel array, can be used to measure the volume of large organs. Partial organ cross-sections can be segmented in the original B-scans, and then combined, without the need for image-based registration, to give the organ volume. The inherent accuracy (not including position sensor and segmentation errors) is demonstrated in simulation to be within +/- 2%. The in vivo precision of the complete system is demonstrated (by repeated observations of a human liver) to be +/- 5%.
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Primary sclerosing cholangitis (PSC) predisposes to cholangiocarcinoma (CC). PET scanning can assess metabolism in vivo. The glucose analogue [18 F]fluoro-2-deoxy-D-glucose (FDG) accumulates in malignant tumours because of high glucose metabolism. PET scanning of the liver was performed after intravenous FDG in nine patients with PSC, six with PSC + CC, and five controls. "Hot spots" with radioactivity accumulation were seen in each PSC + CC patient, but not in the two other groups. Values of net metabolic clearance of FDG, K (ml min-1 100 ml-1 tissue), was in CC hot spots 1.59 to 4.17 (median, 2.34; n = 6); in reference liver tissues of these patients 0.40 to 0.69 (0.49); in PSC 0.23 to 0.53 (0.36); in controls 0.20 to 0.34 (0.31). The difference between K in CC hot spots and the other groups was statistically significant (P < 0.001). FDG-PET may detect small CC tumours and be useful in therapeutic management of PSC.
The effect of acute pretreatment with MK-801 on the binding in vivo of both 3H-N-methylspiperone (NMSP) and 3H-raclopride (RAC) were compared in mice. In the striatum, MK-801 significantly increase 3H-NMSP binding, whereas no significant alterations in 3H-RAC binding were seen. In contrast, binding in the cerebral cortex of both radiolabeled ligands was not changed by MK-801. Kinetic analysis revealed that the increase in 3H-NMSP binding induced by MK-801 was due to an increase in the rate constant k3(k3 = kon.Bmax). In vivo saturation experiments showed that Bmax for 3H-NMSP binding was relatively unchanged and an increase in the apparent association rate constant (kon) was the main reason for an increase in the k3 for 3H-NMSP binding. As 3H-RAC binding is known to be much more sensitive to competitive inhibition than is 3H-NMSP binding, these results strongly suggest that factors other than competition by endogenous dopamine may contribute to changes in receptor binding in vivo caused by NMDA-antagonism.
Competitive inhibition of 3H-raclopride (RAC) and 3H-N-methylspiperone (NMSP) binding against haloperidol, raclopride and NMSP was measured in the mouse striatum. 3H-RAC binding was more sensitive to competitive inhibition by all three compounds compared with 3H-NMSP. For example, 0.3 mg/kg of haloperidol resulted in 95% inhibition of 3H-RAC binding, however only 60% of inhibition of 3H-NMSP binding was found at the same dose of haloperidol. The cross-inhibition experiments using non-radioactive RAC or NMSP as competitors indicated different binding sites for 3H-RAC and 3H-NMSP in mouse striatum. Specifically, about 40% of 3H-NMSP binding was not displaced by treatment with a very high dose of raclopride (3 mg/kg). The time course of inhibition of the specific binding of 3H-RAC and 3H-NMSP were measured following i.p. injection of 0.5 mg/kg of haloperidol. No significant differences in the kinetics of haloperidol inhibition were observed between two radioligands.
Conventional freehand three-dimensional (3-D) ultrasound is a multi-stage process. First, the clinician scans the area of interest. Next, the ultrasound data is used to construct a 3-D voxel array, which can then be visualized by, for example, any-plane slicing. The strict separation of data acquisition and visualization disturbs the interactive nature of the ultrasound examination. Furthermore, some systems require the clinician to wait for an unacceptable amount of time while the voxel array is constructed. In this paper, we describe a novel freehand 3-D ultrasound system which allows accurate acquisition of the raw data and immediate visualization of arbitrary slices through the data. Minimal processing separates the acquisition and visualization processes: in particular, at no stage is a voxel array constructed. Instead, the standard graphics hardware found inside most desktop computers is exploited to synthesize arbitrary slices directly from the raw B-scans.
Three-dimensional freehand ultrasound imaging produces a set of irregularly spaced B-scans, which are typically reconstructed on a regular grid for visualization and data analysis. Most standard reconstruction algorithms are designed to minimize computational requirements and do not exploit the underlying shape of the data. We investigate whether an approximation with splines holds any promise as a better reconstruction method. A radial basis function approximation method is implemented and compared with three standard methods. While the radial basis approach is computationally expensive, it produces accurate reconstructions without the kind of visible artefacts common with the standard methods. The other potential advantages of radial basis functions, such as the direct computation of derivatives, make further investigation worthwhile.
Neuroreceptor imaging by PET or SPECT has been widely applied in the field of neurobiology, from basic to clinical investigations, and has the potential to reveal the neurochemical basis of various neurological and psychiatric diseases as well as to provide new knowledge in the field of neuropharmacology. In contrast to the static nature of in vitro systems, neurotransmission systems in the intact brain constitute part of a dynamic and communicating environment. Thus, it is important to develop new functional imaging methods that reflect neural communications and the dynamism of signal transmission in the living brain. In vivo receptor binding can be altered not only by competitive inhibition by endogenous neurotransmitters but by trans-synaptic effects, and investigation of neural interactions by detection of changes in receptor binding therefore presents a potential method for studying this phenomenon. Recently, several PET studies on in vivo neural interactions using the D2 receptor ligand [11C]-raclopride concluded that the phenomenon was mediated by changes in synaptic endogenous dopamine concentrations that compete with [11C]-raclopride binding for neuroreceptor occupancy. However, a growing body of evidence indicates that these changes in in vivo receptor binding cannot be fully explained by competitive inhibition by endogenous ligand, and alternative mechanisms for the interneuronal modulation of receptor binding are addressed. This review highlights some of the discrepancies observed between in vitro and in vivo receptor binding studies with respect to a number of phenomena, including the heterogeneity of the reaction field surrounding receptors. Quantitative receptor binding studies are usually analyzed by using 'static' binding parameters, such as the Bmax, and KD, which are normally determined by in vitro assays. In addition to these parameters, the apparent association and dissociation rate constants (kon, koff) play equally significant roles in receptor binding in the intact brain is expected. The concepts of "diffusion boundary" and "reaction volume" are introduced, and discussions on some of the discrepancies between in vivo and in vitro receptor binding phenomena are presented.
We studied 36 patients with non-Hodgkin's lymphoma to evaluate the stem cell yield following recovery from intensive dose ifosfamide and etoposide given as mobilization chemotherapy. We also assessed the toxicity of the regimen and engraftment kinetics. All patients had intermediate grade lymphoma and had either failed to achieve a complete remission to induction chemotherapy or had relapsed. Patients received ifosfamide 10 g/m2 IV total dose given over 72 hours, etoposide 150 mg/m2 IV every 12 hours for 6 doses and G-CSF 10 microg/kg/d. Thirty-four patients went on to receive high-dose chemotherapy with BEAM or with CVP and BEAM. A median of 2 (1-10) apheresis was required to reach the target CD34+ count of >4 x 10(6)/kg. A median of 13.1 CD34+ cells/kg (4.1-148) was obtained. Toxicity was limited to mucositis in 3 patients, transient confusion and transient rise in liver function tests in 3 and 2 patients respectively. The median time to engraftment was 10 days (8-17) for all the patients undergoing high-dose chemotherapy. The regimen of intensive dose ifosfamide and etoposide along with G-CSF is well tolerated and in this group of patients has lead to successful stem cell harvests and sustained engraftment.
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Primary sclerosing cholangitis (PSC) predisposes to cholangiocarcinoma (CC), which usually is widespread in the liver at the time of the diagnosis and which has a median survival of approximately 6 months. Positron emission tomography (PET) is a noninvasive scanning method that allows the assessment of metabolism in vivo by means of positron-emitting radiolabeled tracers. [18F]Fluoro-2-deoxy-D-glucose (FDG) is a glucose analogue that accumulates in various malignant tumors because of their high glucose metabolic rates. The purpose of the study was to develop a PET method to detect small CC tumors in patients with PSC. PET scanning of the liver was performed after intravenous injection of 200 MBq FDG in 9 patients with PSC, 6 patients with PSC + CC, and 5 controls. The scanning was performed at successive time intervals for a total of 90 minutes with simultaneous successive arterial blood sampling for radioactivity concentration determination. In each of the PSC + CC patients, 2 to 7 "hot spots" were seen, with volumes of 1.0 to 45 mL (median, 4.4 mL). There were no hot spots in the two other patient groups. The localization of hot spots was confirmed by single-blind evaluation. Data were analyzed by the Gjedde-Patlak plot, yielding values of the net metabolic clearance of FDG, K [mL min(-1) 100 mL(-1) tissue]. In the CC hot spots, maximum K values were 1.59 to 4.17 (median, 2.34; n = 6); in the reference liver tissues of these patients, K values were 0.40 to 0.69 (median, 0.49); in PSC patients, they were 0.23 to 0.53 (median, 0.36); and in controls, they were 0.20 to 0.34 (median, 0.31). The difference between K in CC hot spots and the other groups was statistically significant (P < .001). We conclude that FDG-PET seems to be able to detect small CC tumors and may be useful in the therapeutic management of PSC.
The effects of muscarinic agonist, oxotremorine (0.3 mg/kg), and antagonist, scopolamine (0.5 mg/kg), on in vivo [3H]raclopride (RAC) and [3H]N-methylspiperone (NMSP) binding were investigated. Following tracer administration to control or pretreated mice, binding potentials, and the rate constants k3 and k4 were determined by kinetic analysis. Oxotremorine resulted in a 70% increase in striatal RAC binding potential compared with controls. RAC and NMSP showed almost identical decreases in k3 (40%), whereas k4 for RAC was unexpectedly decreased by 64%. Scopolamine resulted in no significant changes in RAC or NMSP binding. These results, in combination with previous data obtained in reserpinized mice, show that 1) competition by endogenous ligand may not be the only factor influencing the magnitude of apparent in vivo receptor binding, and 2) interneuronal communication may be partly mediated by changes in the rates of ligand-receptor binding.