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Biomedical subjects

T Kling-Petersen

Publications and source records attributed to T Kling-Petersen.

15 recordsLinked to original sources

Virtual reality on the web: the potentials of different methodologies and visualization techniques for scientific research and medical education.

Academic and medical imaging are increasingly using computer based 3D reconstruction and/or visualization. Three-dimensional interactive models play a major role in areas such as preclinical medical education, clinical visualization and medical research. While 3D is comparably easy to do on a high end workstations, distribution and use of interactive 3D graphics necessitate the use of personal computers and the web. Several new techniques have been demonstrated providing interactive 3D via a web browser thereby allowing a limited version of VR to be experienced by a larger majority of students, medical practitioners and researchers. These techniques include QuickTimeVR2 (QTVR), VRML2, QuickDraw3D, OpenGL and Java3D. In order to test the usability of the different techniques, Mednet have initiated a number of projects designed to evaluate the potentials of 3D techniques for scientific reporting, clinical visualization and medical education. These include datasets created by manual tracing followed by triangulation, smoothing and 3D visualization, MRI or high-resolution laserscanning. Preliminary results indicate that both VRML and QTVR fulfills most of the requirements of web based, interactive 3D visualization, whereas QuickDraw3D is too limited. Presently, the JAVA 3D has not yet reached a level where in depth testing is possible. The use of high-resolution laserscanning is an important addition to 3D digitization.

Computer Graphics

Laser 3-D scanning for surface rendering in biomedical research and education.

A technique based on laser scanning is applied to body parts and organs. Laser light is projected onto the surface of objects and recorded by CCD sensors. This is a fast and flexible method for accurately scanning surface geometry. It also allows conversion to NURBS patches. We have, so far, made 'point-cloud' surface renderings from a head model, a plastic brain model, a human brain, moulds of bites and a cranium. The limits, quality, efforts and costs of employing the laser 3-D scanning technique are evaluated. The experiments are currently in progress and results give interesting 3D renderings and attempts to triangulated solid-models.

Brain

3D-brain 2.0--narrowing the gap between personal computers and high end workstations.

UNLABELLED: Recent advances in personal computer hardware and software have pushed the graphic capacity of these easier to use and, more importantly, cheaper computers to a level approximating the current standard of high end workstations. The interactivity and graphic complexity of a modern PC is rapidly approaching the current standard on Silicon Graphics (although with respect to texture mapping, the SGI is still ahead of the PCs). The modern medical student laboring under increasingly higher demands with respect to versatility, not only in basic science and traditional medical knowledge, is also faced with the requirement to learn and understand modern scientific visualization and analytical instruments. Furthermore, basic knowledge of information technology and computer literacy is expected of the next generation medical professionals. These demands forces medical schools to increasingly invest in computers and information technology for educational purposes. Due to common class sizes, these computers are most commonly Windows PCs or Apple Macintoshes. For distance education, telematics or studies at home, personal computer versions of the workstation graphics are a necessity. 3D-Brain 2.0 is an educational software package intended to run on basic personal computers and utilizing modern software technologies such as QuickTime VR 2.0 and VRML 2.0, to provide the students with insight into modern clinical and scientific visualization, focusing on the anatomy and functionality of the human brain. The aim of this paper to test the validity and usefulness of these new visualization techniques. METHODS: 3D-Brain is based on human brains sliced in 1 mm sections (NB. NOT based on NLMs Visual Human). Each slice was photographed, digitized, optimized and aligned using proprietary software. The datasets were then created by manual tracing followed by triangulation, smoothing and 3D visualization using Silicon Graphics computers. For the QuickTime VR project, 684 images with a 10 degrees angle were generated for each scene and ported to an Apple Macintosh computer for further manipulation. VRML code was generated directly from the original dataset. All interactivity was programmed on a Macintosh and subsequently ported to the Windows95 PC platform. The minimum requirements to run the software are either a PowerPC based Macintosh computer or a Pentium based Windows 95 computer with 16 Mb, 16 bit display and a 4 speed CD-ROM. RESULTS AND DISCUSSION: 3D-Brain 2.0 provides medical students at Goteborg University the means to complement traditional teaching using visualization techniques and three-dimensional models. These techniques also serve as an insight into the different clinical means of visualization the student will encounter throughout his/her continued education and professional career. For educational purposes, it has been established that among the tested new visualization techniques, CD-ROM based software utilizing QTVR is still the best methodology to use for pedagogical software. VRML shows promise in porting these software packages to the Web while Open Inventor is the preferred format for research purposes.

Brain

The BRAIN project: an interactive learning tool using desktop virtual reality on personal computers.

The BRAIN-project is an endeavor in using computer aided learning to improve the understanding of the human brain anatomy. The project consists of four parts, each based on modular packages: BRAINIMAGES: Brain atlas consisting of horizontal and frontal brain slices spaced I mm apart enabling the identification of structures and areas of the brain. The software also contains views of the brain's outer surface with all pertinent structures marked. BRAINRADIOLOGY: Visualisation of the brain using CT, MRI and angiography. The different imaging techniques enable the user to explore the brain from several angles and also view the major blood vessels of the brain. NEUROHISTOLOGY: Cells of the brain using histologically stained sections. The program emphasizes the organization of cells in layers and the interaction of different cell types. 3D-BRAIN: Three dimensional reconstructions based on physical slices of a human brain. The reconstructed brain views are made interactive using a simple form of desktop virtual reality: QuickTime VR technology. The user can rotate the different views in all directions producing a 3D effect. The different views are designed to highlight important structures and their organization within the outlined (and semi transparent) brain surface. Contrary to similar applications, the actual three dimensional objects are not based on MRI or CT scans (with comparatively poor resolution), but on tracings made on high resolution images of photographs of actual sections of a postmortem brain. N.B., this approach produces 3D renderings in a more detailed and reliable way. The BRAIN project is designed as a support package for students in preclinical education by supplying additional means for gathering information pertinent to the curriculum. By cross linking, the students can switch from a three dimensional object to a corresponding slice, and then to the relevant histological sample and son on. The software components are based on a modular design enabling easy modification of the various parts and the entire project is designed to run on both Apple Macintosh and MS Windows based PCs.

Anatomy

Effects on locomotor activity after local application of (+)-UH232 in discrete areas of the rat brain.

The preferential dopamine autoreceptor, and slightly D3 preferring, antagonist (+)-UH232 (cis-(+)-(1S,2R)-5-methoxy-1-methyl-2-(n-dipropylamino) tetralin) increases locomotor activity and synaptic dopamine release in the nucleus accumbens and striatum after systemic administration to the rat. As shown in this study, (+)-UH232, was unable to produce an increase in locomotor activity measured for 60 minutes after local administration into the terminal or somato-dendritic regions of the mesolimbic dopamine pathways or into the lateral ventricle. Instead, a dose dependent decrease of spontaneous locomotor activity after local application (0.05-50.0 nmol/side) of (+)-UH232 into the nucleus accumbens, was seen. A similar reduction in locomotor activity was produced by the classical dopamine antagonist raclopride. Analysis of the dose*time interactions on locomotor activity did, however, indicate that there is a significant dose*time interaction after local application of (+)-UH232 into the lateral ventricle and VTA. Raclopride, on the other hand, produced only a weak time dependent effect in the VTA. The potential problem of Leao's spreading depression in micro-injection experiments were considered, however, spreading depression does not seem to influence the effects of (+)-UH232 locally applied into the nucleus accumbens. In conclusion, both (+)-UH232 and raclopride produced a dose dependent decrease in spontaneous locomotor activity when examined as the total activity count over 60 minutes after local application into the N Acc.

8-Hydroxy-2-(di-n-propylamino)tetralin

Effects of dopamine D3 preferring compounds on conditioned place preference and intracranial self-stimulation in the rat.

Compounds showing an in vitro binding preference for the dopamine D3 receptor were tested in two models designed to assess positive reinforcement in the rat: intracranial self-stimulation (ICSS) and conditioned place preference (CPP). R-(+)-7-OH-DPAT, a D3 preferring agonist, inhibited ICSS behaviour over a wide dose range. At higher doses, a facilitation of ICSS was seen. In the CPP model, 7-OH-DPAT was inactive except at the highest dose where a significant change in preference was seen. A dose of R-(+)-7-OH-DPAT, that significantly inhibited ICSS behaviour, was combined with a dose of d-amphetamine, that significantly facilitated ICSS behaviour. Surprisingly, this resulted in a significant synergistic facilitation of the amphetamine response. The putative D3 antagonist, U99194A was inactive in the ICSS model but induced significant place preference. The present results suggest that the dopamine D3 receptor, in contrast to the D2 receptor, has an inhibitory influence on reward mechanisms.

Animals

Effects on locomotor activity after local application of D3 preferring compounds in discrete areas of the rat brain.

Compounds showing an in vitro binding preference for the dopamine D3 vs. D2 receptors were tested for effects on locomotor activity after local application in the nucleus accumbens (N Acc) and the ventral tegmental area (VTA) of the rat brain. R-(+)-7-OH-DPAT, a dopamine D3 preferring agonist, inhibited spontaneous locomotor activity over a wide dose range after injection into the N Acc. A decrease in activity over a wide dose range was also seen after local application into the VTA of both R-(+)-7-OH-DPAT and the dopamine D2 preferring agonist (+)-3-PPP. Furthermore, (+)-3-PPP produced a dose dependent increase in activity after local application into the N Acc. The putative D3 antagonist, U99194A, with a 30 fold preference for the dopamine D3 vs. D2 receptor, produced an increase in activity when injected into the N Acc. A similar pattern were seen after infusion into the lateral ventricle. Local application into the VTA did, however, not produce any significant effects. The present results support the hypothesis that dopamine D3 receptors (in contrast to the D2 receptors) are mainly postsynaptically located where they display an inhibitory action on locomotor activity.

Animals

Behavioral and neurochemical data suggest functional differences between dopamine D2 and D3 receptors.

In an in vitro model for mitogenic activity in cloned Chinese hamster ovary (CHO) cells expressing rat dopamine D2 or D3 receptors, the EC50D2/EC50D3 ratios for the agonists, apomorphine, (+)-3-hydroxy-N-n-propyl-phenylpiperidine ((+)-3-PPP), quinpirole, R-(+)-7-hydroxy-2-(di-n-propylamino)tetralin (R-(+)-7-OH-DPAT) and pramipexole (SND919) were found to be 0.36, 0.41, 1.3, 3.7 and 7.0, respectively. In locomotor activity experiments with actively exploring rats, the more dopamine D3 preferring agonists, R-(+)-7-OH-DPAT and pramipexole, were most efficacious to reduce locomotion. The hypoactivity was also observed at doses that did not affect brain dopamine synthesis rate (DOPA accumulation) or release (measured in in vivo dialysis experiments). In contrast, for apomorphine, (+)-3-PPP and quinpirole there was a closer correlation between doses that reduced exploratory activity and doses that reduced brain dopamine release and synthesis. The present data support the hypothesis that the functional dopamine D3 receptor is a postsynaptic receptor inhibitory on rat locomotion.

Analysis of Variance

The preferential dopamine autoreceptor antagonist (+)-UH232 antagonizes the positive reinforcing effects of cocaine and d-amphetamine in the ICSS paradigm.

The dopamine autoreceptor and D3 preferring antagonist [cis-(+)-5-methoxy-1-methyl-2-(di-n-propylamino)tetralin] (+)-UH232, exerts weak stimulatory effects when tested in locomotor activity experiments using habituated animals. (+)-UH232 also blocks d-amphetamine-, cocaine-, and apomorphine-induced hyperactivity, but fails to induce catalepsy. Thus, the behavioral effects of (+)-UH232 appear to be dependent upon the baseline activity of the animal. The antagonistic properties of (+)-UH232 were studied in the intracranial self-stimulation (ICSS) technique in the rat. (+)-UH232 and haloperidol produced inhibitory effects over a wide dose range. Cocaine, GBR12909 and d-amphetamine clearly lowered ICSS thresholds, indicating stimulatory effects. (+)-UH232 antagonized the stimulatory effects of cocaine, GBR12909, and d-amphetamine, whereas haloperidol, at a dose producing an inhibition similar to (+)-UH232, was significantly weaker in antagonizing cocaine- or d-amphetamine-induced stimulation. This difference between (+)-UH232 and haloperidol with respect to stimulant-blocking ability, support the concept that the effects of (+)-UH232 are not representative of either classical DA agonists or DA antagonists.

8-Hydroxy-2-(di-n-propylamino)tetralin

GABAB-receptor activation alters the firing pattern of dopamine neurons in the rat substantia nigra.

Previous electrophysiological experiments have emphasized the importance of the firing pattern for the functioning of midbrain dopamine (DA) neurons. In this regard, excitatory amino acid receptors appear to constitute an important modulatory control mechanism. In the present study, extracellular recording techniques were used to investigate the significance of GABAB-receptor activation for the firing properties of DA neurons in the substantia nigra (SN) in the rat. Intravenous administration of the GABAB-receptor agonist baclofen (1-16 mg/kg) was associated with a dose-dependent regularization of the firing pattern, concomitant with a reduction in burst firing. At higher doses (16-32 mg/kg), the firing rate of the DA neurons was dose-dependently decreased. Also, microiontophoretic application of baclofen regularized the firing pattern of nigral DA neurons, including a reduction of burst firing. Both the regularization of the firing pattern and inhibition of firing rate produced by systemic baclofen administration was antagonized by the GABAB-receptor antagonist CGP 35348 (200 mg/kg, i.v.). The GABAA-receptor agonist muscimol produced effects on the firing properties of DA neurons that were opposite to those observed following baclofen, i.e., an increase in firing rate accompanied by a decreased regularity. The NMDA receptor antagonist MK 801 (0.4-3.2 mg/kg, i.v.) produced a moderate, dose-dependent increase in the firing rate of the nigral DA neurons as well as a slightly regularized firing pattern. Pretreatment with MK 801 (3.2 mg/kg, i.v., 3-10 min) did neither promote nor prevent the regularization of the firing pattern or inhibition of firing rate on the nigral DA neurons produced by baclofen. The present results clearly show that GABAB-receptors can alter the firing pattern of nigral DA neurons, hereby counterbalancing the previously described ability of glutamate to induce burst firing activity on these neurons.

Animals

A simple computer-based method for performing and analyzing intracranial self-stimulation experiments in rats.

Intracranial self-stimulation (ICSS) in the rat is a useful tool for studying the importance of various brain monoamines in positive reinforcement. The effects of compounds interacting with dopaminergic neurotransmission is measurable by studying the changes of reward thresholds. By computerisation of the analysis of these thresholds, standardisation and reproducibility is greatly enhanced. The use of an object-oriented programming language simplifies the programming of a specific application and it provides scientists without formal training in computer programming the means to create their own software. A system for the acquisition, execution, analysis and storage of ICSS experiments is described. The hardware is based on Apple Macintosh computers, interfaced to the test chambers and physiological stimulators using a plug-in card supporting A/D, D/A, digital I/O and timer functions. The software written in G (LabVIEW) provides the user with a graphically based 'Virtual Instrument' performing all aspect of the ICSS experiment. The software performs threshold analysis immediately after completion of the ICSS experiment, thereby greatly reducing the total time previously needed to evaluate these experiments. The graphical approach used in LabVIEW allows the programmer to make fast and simple alterations to suit different experimental problems.

Animals

Effects of the preferential dopamine autoreceptor antagonist (+)-AJ76 in the intracranial self-stimulation paradigm.

As revealed by locomotor activity experiments in rodents, cis-(1S,2R)-5-methoxy-1-methyl-(2-n-propylamino)tetralin [(+)-AJ76] is a preferential dopamine autoreceptor antagonist that produces stimulatory or weak inhibitory behavioral effects in animals that display low or high baseline activity, respectively. In the present study, the possible positive reinforcing properties of (+)-AJ76 were studied by means of the intracranial (median forebrain bundle) self-stimulation (ICSS) technique in rats. The current intensity of the electrical stimuli was used as the independent variable. The resulting rate/intensity curves were analyzed by computer, and the half-maximal response (called EC50) was calculated for each animal. When starting on a suprathreshold current intensity, (+)-AJ76 dose dependently (3.1-52.0 microM/kg, SC) increased the EC50 without producing any apparent motor deficits like muscular rigidity or catalepsy. A clear-cut and more potent inhibitory action was also noted for haloperidol (0.033-0.133 microM/kg, SC) and the di-N-methyl analog of (+)-AJ76 called (+)-AJ118 (0.8-3.5 microM/kg, SC), while d-amphetamine (1.4 or 5.4 microM/kg, SC) decreased the EC50 values. In the second experiment, animals were subjected to a subthreshold current intensity for 30 min. The intensity was set to produce a response of 15% or less of maximal, shaping response rate for the respective animals. Of these 22 animals, 10 responded with a stimulation, while the ICSS response was inhibited in the others. We did not, however, get consistent results in all rats tested. In summary, this study shows that (+)-AJ76 appears to lack positive reinforcing properties comparable to those produced by classical stimulants such as d-amphetamine.

Animals

Quantification of axonally transported material using cytofluorimetric scanning.

This paper describes in detail a cytofluorimetric scanning technique used for studying amounts of material axonally transported in antero- and retrograde direction in peripheral nerves. Operating procedures, preparation of tissues and instrumental set-up are described. The basis for quantification of material in a nerve section treated for immunofluorescence is discussed. The reliability of the method has been tested by comparing results with biochemical data. There are several advantages of the technique. (1) Many different substances can be studied in one single nerve segment, thus reducing biological variation and costs. (2) Both morphological data and quantitative figures can be obtained; following scanning the section can be photographed. (3) The method can also be used on studies in the central nervous system and on tissue cultures, since it is possible to scan on single axons or bundles of fibres.

Animals

Serotonin-producing carcinoid tumour cells in long-term culture. Studies on serotonin release and morphological features.

Tumour cells from a hepatic metastasis of a midgut carcinoid tumour were studied during 240 days of culture. A cell line could not be established, but the cells regularly formed large clusters and islets. The spontaneous release of serotonin (5-HT) and neuropeptide K-like immunoreactivity from cultures were followed. The amine and the peptide levels were unstable without evident covariation. The response to stimulation with noradrenaline and isoprenaline was studied during the culture period. The tumour cells released 5-HT selectively at stimulation with isoprenaline. This responsiveness also showed considerable variation with long periods of quiescence. Ultrastructurally the tumour cells showed a certain degree of polarization with apical microvilli and a supranuclear Golgi apparatus. When studied by confocal laser scanning the tumour cells were demonstrated to be cylindrical in shape with a cytoplasmic attachment to the matrix.

Carcinoid Tumor