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Computer based methodology for construction of orthodontic arch wire templates.

This paper presents the details and logic of two Fortran computer programs. The program, BRACKET, is designed to evaluate the constant relationship among teeth and orthodontic brackets to which an arch wire is adapted. The program, WIRE, is used to initially fit brackets to teeth using the constants derived in BRACKETS, based upon a series of orthogonal transformations. Subsequently, an orthodontic arch wire is fitted through the brackets, and the results are displayed using computer graphics. It is anticipated that the system would be useful in the orthodontic clinical setting as an aid in arch wire formation. The graphics produce a template which incorporates essential points to consider in arch wire formation, namely, perimeter length, lateral widths, symmetry, and appropriate arch form for the patient.

Computers↗

Model-based surgical planning and simulation of cranial base surgery.

Plastic skull models of seven individual patients were fabricated by stereolithography from three-dimensional data based on computed tomography bone images. Skull models were utilized for neurosurgical planning and simulation in the seven patients with cranial base lesions that were difficult to remove. Surgical approaches and areas of craniotomy were evaluated using the fabricated skull models. In preoperative simulations, hand-made models of the tumors, major vessels and nerves were placed in the skull models. Step-by-step simulation of surgical procedures was performed using actual surgical tools. The advantages of using skull models to plan and simulate cranial base surgery include a better understanding of anatomic relationships, preoperative evaluation of the proposed procedure, increased understanding by the patient and family, and improved educational experiences for residents and other medical staff. The disadvantages of using skull models include the time and cost of making the models. The skull models provide a more realistic tool that is easier to handle than computer-graphic images. Surgical simulation using models facilitates difficult cranial base surgery and may help reduce surgical complications.

Adult↗

Digital X-ray apparatus especially designed for precise biometry in stereotactic surgical procedures.

Modern stereotactic surgical procedures were developed mainly because digital CT image gave us the opportunity to recognize the morphology and the site of a brain lesion, and, at the same time, CT offered a very easy and reliable way to calculate target coordinates because the brain scans are digital maps. Digital x-ray image obtained with an x-ray-intensifier and a TV Analog/Digital converter is not suitable for stereotactic use because image distortion is multifactorial and it is impossible to rectify. We have developed a new apparatus (Neurogil) for intra-operative use that is able to produce a digital image on a display, the measures displayed match exactly with the patient's brain. A linear array of 1024 photodiodes is working in front of an x-ray source and it collects the density image of the patient's head positioned between them. It shows the patient's head with the stereotactic frame exactly as a radiogram, but no distortion is present. Digital brain angiograms are possible with electronic subtraction, mathematical enhancement and with a stereoscopic view on a particular display. Any kind of mathematical calculation or computer-graphic application is possible. A special software was developed for stereotactic closed and open surgery.

Cephalometry↗

Design of anticancer drugs using modeling techniques.

Flexibility of intercalation site geometries within a B-DNA helix was investigated in the twist-shift plane using energy minimization methods. The parameters optimized included sugar conformation, the glycosidic angles and phosphodiester torsion angles. Our calculations show several regions of energetically favorable intercalation geometries in the twist-shift plane. Modeling studies using interactive computer graphics and electrostatic potential surface compatibility provided initial hypotheses for the structures of the drug-DNA complexes. These hypotheses were supported and extended by energy minimizations of these complexes. Binding positions, conformational features and relative minimum binding energies of two anticancer drugs, mitoxantrone and bisantrene, were computed for intercalation complexes with DNA in the theoretically defined intercalation sites. Mitoxantrone intercalates DNA from the minor groove and the side chain OH or NH groups are involved in hydrogen bonds with the main chain phosphate groups of DNA, thereby cross-linking the complementary strands. The hydroxyl groups of mitoxantrone can also participate in hydrogen bonding with phosphate oxygens of another chain, thereby cross-linking DNA helices. Bisantrene intercalates DNA favorably from the major groove and the NH group of the dihydroimidazole ring can participate in hydrogen bonding with the phosphate oxygens of the backbone. These models are consistent with the physicochemical and electron microscopic studies of the interaction of mitoxantrone and bisantrene with DNA. Our results are now being used to guide the design of novel anticancer drugs that should interact with DNA in a manner similar to that proposed for our representative drugs.

Anthracenes↗

Virtual reality in surgical arthroscopic training.

Arthroscopy has become an irreplaceble method in diagnostics. The arthroscope, with optics and light source, and the exploratory probe are inserted into the knee joint through two small incisions underneath the patella. Currently, the skills required for arthroscopy are taught through hands-on clinical experience. Therefore, the Fraunhofer-Institut fuer Graphische Datenverarbeitung in Darmstadt, in cooperation with the Berufsgenossenschaftliche Unfallklinik Frankfurt am Main, developed a highly interactive medical training system for arthroscopy through computer graphics and virtual reality (VR) techniques. Two main issues are addressed: the three-dimensional (3-D) reconstruction process and the 3-D interaction. The goal of the reconstruction process is to obtain a realistic representation of the knee joint derived from a magnetic resonance image sequence suitable for computer simulation. Moreover, the 3-D interaction of the training system must stimulate real arthroscopy, providing an intuitive handling of the instruments.

Arthroscopy↗

The applicability of holography in forensic identification: a fusion of the traditional optical technique and digital technique.

In this study, the applicability of holography in the 3-dimensional recording of forensic objects such as skulls and mandibulae, and the accuracy of the reconstructed 3-D images, were examined. The virtual holographic image, which records the 3-dimensional data of the original object, is visually observed on the other side of the holographic plate, and reproduces the 3-dimensional shape of the object well. Another type of holographic image, the real image, is focused on a frosted glass screen, and cross-sectional images of the object can be observed. When measuring the distances between anatomical reference points using an image-processing software, the average deviations in the holographic images as compared to the actual objects were less than 0.1 mm. Therefore, holography could be useful as a 3-dimensional recording method of forensic objects. Two superimposition systems using holographic images were examined. In the 2D-3D system, the transparent virtual holographic image of an object is directly superimposed onto the digitized photograph of the same object on the LCD monitor. On the other hand, in the video system, the holographic image captured by the CCD camera is superimposed onto the digitized photographic image using a personal computer. We found that the discrepancy between the outlines of the superimposed holographic and photographic dental images using the video system was smaller than that using the 2D-3D system. Holography seemed to perform comparably to the computer graphic system; however, a fusion with the digital technique would expand the utility of holography in superimposition.

Adult↗

Fast voxel and polygon ray-tracing algorithms in intensity modulated radiation therapy treatment planning.

We present work on combining three algorithms to improve ray-tracing efficiency in radiation therapy dose computation. The three algorithms include: An improved point-in-polygon algorithm, incremental voxel ray tracing algorithm, and stereographic projection of beamlets for voxel truncation. The point-in-polygon and incremental voxel ray-tracing algorithms have been used in computer graphics and nuclear medicine applications while the stereographic projection algorithm was developed by our group. These algorithms demonstrate significant improvements over the current standard algorithms in peer reviewed literature, i.e., the polygon and voxel ray-tracing algorithms of Siddon for voxel classification (point-in-polygon testing) and dose computation, respectively, and radius testing for voxel truncation. The presented polygon ray-tracing technique was tested on 10 intensity modulated radiation therapy (IMRT) treatment planning cases that required the classification of between 0.58 and 2.0 million voxels on a 2.5 mm isotropic dose grid into 1-4 targets and 5-14 structures represented as extruded polygons (a.k.a. Siddon prisms). Incremental voxel ray tracing and voxel truncation employing virtual stereographic projection was tested on the same IMRT treatment planning cases where voxel dose was required for 230-2400 beamlets using a finite-size pencil-beam algorithm. Between a 100 and 360 fold cpu time improvement over Siddon's method was observed for the polygon ray-tracing algorithm to perform classification of voxels for target and structure membership. Between a 2.6 and 3.1 fold reduction in cpu time over current algorithms was found for the implementation of incremental ray tracing. Additionally, voxel truncation via stereographic projection was observed to be 11-25 times faster than the radial-testing beamlet extent approach and was further improved 1.7-2.0 fold through point-classification using the method of translation over the cross product technique.

Algorithms↗

Conformational analysis of the antiulcer drug pirenzepine. X-ray investigations, molecular mechanics and quantum mechanical calculations and comparisons with structurally or pharmacologically related compounds.

The crystal structures of the antiulcer drug 5,11-dihydro-11-[(4-methyl-1-piperazinyl) acetyl]-6H-pyrido[2,3-b] [1,4]benzodiazepin-6-one dihydrochloride (pirenzepine dihydrochloride, L-S 519 CL 2, Gastrozepin) and its monoprotonated form (pirenzepine monohydrochloride, L-S 519 CL) were determined by X-ray analysis. Molecular mechanics (MMPI) and semiempirical quantum chemical (MNDO) calculations showed that the calculated minimum energy conformations of the tricycle and of the exocyclic amide group are in agreement with the crystal structures. The conformational energies of pirenzepine as a function of four important torsional angles were calculated using different semiempirical quantum chemical methods with the CNDO/2 (complete neglect of differential overlap)-, MNDO (modified neglect of diatomic overlap)- and PCILO (perturbative configuration interaction using localized orbitals)-approximations. The conformation of one local energy minimum corresponds closely to the crystal structure of pirenzepine monohydrochloride. This conformation has a spatial arrangement which is analogous to a single consistent conformation known from the literature of 24 anticholinergic agents determined from their crystal structures by a computer graphics analysis. On the other hand there are no structural relationships of any low energy conformation of pirenzepine to conformations of other classes of tricyclic compounds which could rationalize their antidepressant, neuroleptic or antihistaminic activity. This finding explains the absence of any central effect of pirenzepine following intracerebral application. The computational elucidation of the conformational requirements for the interaction with the muscarinic receptors may be helpful for the interpretation of the selectivity of pirenzepine within the muscarinic system.

Antidepressive Agents, Tricyclic↗

Crystal structure of YecO from Haemophilus influenzae (HI0319) reveals a methyltransferase fold and a bound S-adenosylhomocysteine.

The crystal structure of YecO from Haemophilus influenzae (HI0319), a protein annotated in the sequence databases as hypothetical, and that has not been assigned a function, has been determined at 2.2-A resolution. The structure reveals a fold typical of S-adenosyl-L-methionine-dependent (AdoMet) methyltransferase enzymes. Moreover, a processed cofactor, S-adenosyl-L-homocysteine (AdoHcy), is bound to the enzyme, further confirming the biochemical function of HI0319 and its sequence family members. An active site arginine, shielded from bulk solvent, interacts with an anion, possibly a chloride ion, which in turn interacts with the sulfur atom of AdoHcy. The AdoHcy and nearby protein residues delineate a small solvent-excluded substrate binding cavity of 162 A(3) in volume. The environment surrounding the cavity indicates that the substrate molecule contains a hydrophobic moiety and an anionic group. Many of the residues that define the cavity are invariant in the HI0319 sequence family but are not conserved in other methyltransferases. Therefore, the substrate specificity of YecO enzymes is unique and differs from the substrate specificity of all other methyltransferases sequenced to date. Examination of the Enzyme Commission list of methyltransferases prompted a manual inspection of 10 possible substrates using computer graphics and suggested that the ortho-substituted benzoic acids fit best in the active site.

Binding Sites↗

Nicotinic acetylcholine receptor: a structural model for alpha-subunit peptide 188-201, the putative binding site for cholinergic agents.

A peptide corresponding to amino acid sequence 188-201 of the alpha-subunit of Torpedo AChR binds alpha-Bgtx. The S-S bridge between Cys 192 and 193 is essential for the binding as Tyr in position 189. The same sequence 188-201 corresponding to human AChR, which instead of Tyr has a Thr in position 189, binds alpha-Bgtx with a much lower efficiency. Monoclonal antibodies raised against Torpedo peptide 188-201 recognize Torpedo AChR and antibodies against Torpedo AChR recognize peptide 188-201 indicating that the synthetic peptide and the corresponding sequence in the native molecule share some immunological epitopes. With computer graphics and energy refinement a molecular model of this peptide has been elaborated.

Amino Acid Sequence↗

Preferential induction of the rat hepatic P450 I proteins by the food carcinogen 2-amino-3-methyl-imidazo[4,5-f]quinoline.

1. Administration of the food carcinogen, 2-amino-3-methyl-imidazo[4,5-f]quinoline (IQ) to rats gave rise to significant dose-dependent increases in the microsomal O-deethylations of ethoxycoumarin and ethoxyresorufin but had no effect on the O-dealkylation of pentoxyresorufin and the NADPH-dependent reduction of cytochrome c, and decreased the N-demethylation of dimethylnitrosamine. Microsomal cytochrome b5 and total cytochrome P-450 levels decreased following the administration of the carcinogen. 2. Hepatic microsomal preparations from IQ-treated animals were much more efficient than control in activating the premutagen 2-amino-6-methyldipyrido[1,2-a:3',2'-d]imidazole to mutagenic intermediates in the Ames test. 3. Immunoquantification of two of the major families of cytochrome P-450, namely P450 I and P450 II B, using ELISA techniques showed that treatment with IQ induced the apoprotein levels of the P450 I family but not of P450 II B. 4. Immunoblot analysis employing polyclonal antibodies against P450 I revealed that IQ induced both isoenzymes of this family, namely P450 I A1 and A2. 5. It is concluded that IQ is an inducer of the rat hepatic monooxygenases, selectively inducing the P450 I family as predicted by a computer-graphic analysis of its dimensions which showed that it is a large, essentially planar, molecule.

Animals↗

Non-radiological technique for 3D imaging of intestinal endoscopes: computerised graphical 3D representation of endoscope and skeleton.

Colorectal cancer is a common malignancy but as yet there is no agreement regarding the optimal method for screening. Colonoscopy is theoretically the investigation of choice. The examination can, however, be difficult to perform and the average trainee requires at least 200 supervised examinations to become proficient. Colonoscopy takes on average about half an hour per patient and sedation is normally required because of painful instrument looping. The authors previously developed a non-radiological method of visualising the path of the endoscope using magnetic drive coils under the patient and a chain of sensors in the biopsy channel of the instrument. The computer-generated grey-scale images produced in real time were deemed unsatisfactory and the anatomical markers confusing. A new computer graphics system is described in which a much more realistic endoscope and, if necessary, skeleton can be produced. The wire-frame octagonal representation should help in the detailed analysis of colonoscopy using existing endoscopes and aid in future computer design and testing of novel instruments incorporating worm or snake-like properties.

Colonoscopy↗

Motion perimetry identifies nerve fiber bundlelike defects in ocular hypertension.

OBJECTIVE: To determine whether patients with ocular hypertension (OHT) have elevated motion perimetry thresholds. DESIGN: Motion perimetry uses a customized computer graphics program to detect the ability to identify a coherent shift in position of 50% of dots in a defined circular area against a background of fixed dots. Motion size threshold is defined as the smallest circular area in which dot motion is detected. Subjects respond by touching the area of the computer monitor with a light pen where motion stimuli are perceived. Reaction times (milliseconds) to stimuli and localization error (number of pixels from target center) are also obtained for each trial. SETTING: University hospital ophthalmology clinic. PATIENTS OR OTHER PARTICIPANTS: Twenty-seven patients with OHT and 27 age-matched normal subjects. One eye was tested in each subject. MAIN OUTCOME MEASURES: Random dot motion stimuli size thresholds and total deviation probability plot data, reaction times, and spatial localization errors. RESULTS: The patients with OHT had more abnormal test points in the total deviation probability plot analysis compared with the controls (P < .001, chi 2). The abnormal test points were concentrated in the superior and inferior nasal regions. Six subjects had nerve fiber bundlelike defects to motion stimuli. Six subjects (5 overlapping with the probability plot analysis) had abnormal glaucoma hemifield test results. The patients with OHT also had significantly greater localization errors. CONCLUSION: Motion threshold perimetry may be a more sensitive method to detect visual field abnormalities in OHT than conventional automated perimetry.

Adult↗

Three-dimensional reconstruction of cells from serial sections and whole-cell mounts using multilevel contouring of stereo micrographs.

A comprehensive computer-graphics-based system (STERECON) is described for tracing and digitizing contours from individual or stereopair electron micrographs. The contours are drawn in parallel planes within the micrographs. Provision is also made for tracing and digitizing in full three-dimensional (3-D) coordinates in any direction along linear structures such as cytoskeletal elements. The stereopair micrographs are viewed in combination with the contours being traced on a graphics terminal monitor. This is done either by projecting original electron micrograph (EM) negatives onto a screen and optically combining these images with contour lines being drawn on the monitor, or by first digitizing the images and displaying them directly on the monitor along with the contour lines. Prior image digitization allows computer enhancement of the structures to be contoured. Correction and alignment routines are included to deal with variable section thickness, section distortion and mass loss, variations in photography in the electron microscope, and terminal screen curvature when combining projected images with contour lines on the monitor. The STERECON system organizes and displays the digitized data from successive sections as a 3-D reconstruction. Reconstructions can be viewed in any orientation as contour stacks with hidden lines removed; as wire-frame models; or as shaded, solid models with variable lighting, transparency, and reflectivity. Volumes and surface areas of the reconstructed objects can be determined. Particular attention was paid to making the system convenient for the biological user. Users are given a choice of three different stereo-viewing methods.

Animals↗

Using motion perimetry to detect visual field defects in patients with idiopathic intracranial hypertension: a comparison with conventional automated perimetry.

Motion perimetry, a method of visual field testing that uses computer graphics to measure motion perception, quantitates a subject's ability to detect a coherent shift in position of dots in a defined circular area against a background of fixed dots. Motion size threshold is defined as the smallest detectable circular target in which dot motion is detected. Subjects respond by touching a computer monitor screen with a light pen, first when they see a target (reaction time) and a second time where motion targets are detected (localization). Reaction time (msec) to the stimulus and localization error (number of pixels from target center) are then calculated and stored. We tested on eye in each of 20 idiopathic intracranial hypertension (IIH) patients and 40 age-matched normal subjects by conventional automated perimetry (Humphrey visual field analyzer, program 24-2) and motion perimetry. Pointwise probability plots of individual abnormal test points for size threshold responses were generated for the IIH patients based on the 95% confidence limits of the normal subject responses. An analysis of the subjects' visual field pairs (motion versus conventional automated perimetry) was performed based on these probability plots. The IIH patients had an elevated mean motion threshold (p < 0.001) and reaction time (p < 0.001) compared with the normal subjects. There were no significant differences for the localization errors. Based on the probability plot analysis, there was good correlation of the visual field defects between the two perimetry tests. In addition, motion perimetry identified nerve fiber bundle-shaped defects in nine patients in whom they were not detected with conventional automated perimetry.

Adult↗

Dosimetric aspects in stereotactic radiotherapy using small shielded sources.

In stereotactic irradiation by external beams there are many problems involved with dosimetry of small fields, three-dimensional representation of dose distribution, radiobiological involvement of tissue response to total dose and fractionation. Dosimetric problems arise by critical dimension of dosimetric chambers and by difficulties of films calibration. The amount of data required for a correct three-dimensional simulation of isodose curves, tumor and anatomical structures require a very speed computer system, sophisticated computer graphic techniques and calculation algorithm. By use the linear quadratic model of cell survival, maps of combined dose and biological effect (isoeffect curves) are also obtained.

Humans↗

Random dot motion stimuli are more sensitive than light stimuli for detection of visual field loss in ocular hypertension patients.

PURPOSE: To determine whether motion detection perimetry or luminance size threshold perimetry (a test using the motion perimetry method with luminance stimuli) is more sensitive in detecting visual loss in ocular hypertension patients. METHODS: Motion perimetry uses a customized computer graphics program to detect a subject's ability to identify a coherent shift in position of moving dots in a defined circular area against a background of fixed dots. Motion size threshold is defined as the smallest circular area within which dot motion is detected. Patients respond by touching the area of the computer monitor where they perceive the stimulus with a light pen. The localization errors are measured as the number of pixels from target center for each trial. Luminance size threshold perimetry uses the same technique except the background is dark gray and the stimuli are filled lighter gray circles. We tested one eye in each of 27 ocular hypertension patients and 27 age-matched normal subjects with both tests. Our main outcome measures were motion and luminance size thresholds, total deviation probability plot data, and spatial localization errors. RESULTS: With the total deviation probability plot analysis, the ocular hypertension patients had a greater number of abnormal test locations with motion perimetry stimuli than with luminance stimuli. The abnormal test points were located most often in the superior and inferior nasal regions. Six subjects had nerve fiber bundle-like defects to motion stimuli whereas three patients had defects with luminance size threshold perimetry. The ocular hypertension patients had significantly greater localization errors than the controls with both tests. CONCLUSIONS: Using a size thresholding technique in ocular hypertension patients, random dot motion stimuli appear to be more sensitive than luminance stimuli. Errors in stimulus localization are significantly increased in ocular hypertension patients, independent of the stimulus (motion or luminance) used.

Adult↗

Brain surgery simulation system using VR technique and improvement of presence.

A computer aided brain surgery system using virtual reality techniques is developed. This system is aimed to be used to support the surgeons' decision for the operational strategies, or used in the training of medical students to learn how to operate the brain surgery for the patients. In constructing the whole system, high speed graphical computer is equipped. For input 3D data from MRI or CT are used to display 3D images, HMD (head-mounted display) and 3D CRT display with glass are equipped. To improve the 3D images, colors and optical properties of the voxel are refined.

Brain↗