Biomedical subjects

R Fahrig

Publications and source records attributed to R Fahrig.

At least 19 recordsLinked to original sources

PubMed2005

Performance of a static-anode/flat-panel x-ray fluoroscopy system in a diagnostic strength magnetic field: a truly hybrid x-ray/MR imaging system.

Minimally invasive procedures are increasing in variety and frequency, facilitated by advances in imaging technology. Our hybrid imaging system (GE Apollo flat panel, custom Brand x-ray static anode x-ray tube, GE Lunar high-frequency power supply and 0.5 T Signa SP) provides both x-ray and MR imaging capability to guide complex procedures without requiring motion of the patient between two distant gantries. The performance of the x-ray tube in this closely integrated system was evaluated by modeling and measuring both the response of the filament to an externally applied field and the behavior of the electron beam for field strengths and geometries of interest. The performance of the detector was assessed by measuring the slanted-edge modulation transfer function (MTF) and when placed at zero field and at 0.5 T. Measured resonant frequencies of filaments can be approximated using a modified vibrating beam model, and were at frequencies well below the 25 kHz frequency of our generator for our filament geometry. The amplitude of vibration was not sufficient to cause shorting of the filament during operation within the magnetic field. A simple model of electrons in uniform electric and magnetic fields can be used to estimate the deflection of the electron beam on the anode for the fields of interest between 0.2 and 0.5 T. The MTF measured at the detector and the DQE showed no significant difference inside and outside of the magnetic field. With the proper modifications, an x-ray system can be fully integrated with a MR system, with minimal loss of image quality. Any x-ray tube can be assessed for compatibility when placed at a particular location within the field using the models. We have also concluded that a-Si electronics are robust against magnetic fields. Detailed knowledge of the x-ray system installation is required to provide estimates of system operation.

Electromagnetic Fields↗

PubMed2003

First use of a truly-hybrid X-ray/MR imaging system for guidance of brain biopsy.

The use of a new hybrid imaging system for guidance of a brain biopsy is described. The system combines the strengths of MRI (soft-tissue contrast, arbitrary plane selection) with those of x-ray fluoroscopy (high-resolution real-time projection images, clear portrayal of bony structures) and allows switching between the imaging modalities without moving the patient. The biopsy was carried out using x-ray guidance for direction of the needle through the foramen ovale and MR guidance to target the soft-tissue lesion. Appropriate samples were acquired. The system could be particularly effective for guidance of those cases where motion, swelling, resection and other intra-operative anatomical changes cannot be accounted for using traditional stereotactic-based imaging approaches.

Adult↗

PubMed2001

A truly hybrid interventional MR/X-ray system: feasibility demonstration.

A system enabling both x-ray fluoroscopy and MRI in a single exam, without requiring patient repositioning, would be a powerful tool for image-guided interventions. We studied the technical issues related to acquisition of x-ray images inside an open MRI system (GE Signa SP). The system includes a flat-panel x-ray detector (GE Medical Systems) placed under the patient bed, a fixed-anode x-ray tube overhead with the anode-cathode axis aligned with the main magnetic field and a high-frequency x-ray generator (Lunar Corp.). New challenges investigated related to: 1) deflection and defocusing of the electron beam of the x-ray tube; 2) proper functioning of the flat panel; 3) effects on B0 field homogeneity; and 4) additional RF noise in the MR images. We have acquired high-quality x-ray and MR images without repositioning the object using our hybrid system, which demonstrates the feasibility of this new configuration. Further work is required to ensure that the highest possible image quality is achieved with both MR and x-ray modalities.

Brain↗

PubMed2001

Truly hybrid interventional MR/X-ray system: investigation of in vivo applications.

RATIONALE AND OBJECTIVES: The purpose of this study was to provide in vivo demonstrations of the functionality of a truly hybrid interventional x-ray/magnetic resonance (MR) system. MATERIALS AND METHODS: A digital flat-panel x-ray system (1,024(2) array of 200 microm pixels, 30 frames per second) was integrated into an interventional 0.5-T magnet. The hybrid system is capable of MR and x-ray imaging of the same field of view without patient movement. Two intravascular procedures were performed in a 22-kg porcine model: placement of a transjugular intrahepatic portosystemic shunt (TIPS) (x-ray-guided catheterization of the hepatic vein, MR fluoroscopy-guided portal puncture, and x-ray-guided stent placement) and mock chemoembolization (x-ray-guided subselective catheterization of a renal artery branch and MR evaluation of perfused volume). RESULTS: The resolution and frame rate of the x-ray fluoroscopy images were sufficient to visualize and place devices, including nitinol guidewires (0.016-0.035-inch diameter) and stents and a 2.3-F catheter. Fifth-order branches of the renal artery could be seen. The quality of both real-time (3.5 frames per second) and standard MR images was not affected by the x-ray system. During MR-guided TIPS placement, the trocar and the portal vein could be easily visualized, allowing successful puncture from hepatic to portal vein. CONCLUSION: Switching back and forth between x-ray and MR imaging modalities without requiring movement of the patient was demonstrated. The integrated nature of the system could be especially beneficial when x-ray and MR image guidance are used iteratively.

Animals↗

PubMed2001

Filtered backprojection for modifying the impulse response of circular tomosynthesis.

A filtering technique has been developed to modify the three-dimensional impulse response of circular motion tomosynthesis to allow the generation of images whose appearance is like those of some other imaging geometries. In particular, this technique can reconstruct images with a blurring function which is more homogeneous for off-focal plane objects than that from circular tomosynthesis. In this paper, we describe the filtering process, and demonstrate the ability to alter the impulse response in circular motion tomosynthesis from a ring to a disk. This filtering may be desirable because the blurred out-of-plane objects appear less structured.

Animals↗

PubMed2001

Clinical fluoroscopic fiducial-based registration of the vertebral body in spinal neuronavigation.

We present a system involving a computer-instrumented fluoroscope for the purpose of 3D navigation and guidance using pre-operative diagnostic scans as a reference. The goal of the project is to devise a computer-assisted tool that will improve the accuracy, reduce risk, minimize the invasiveness, and shorten the time it takes to perform a variety of neurosurgical and orthopedic procedures of the spine. For this purpose we propose an apparatus that will track surgical tools and localize them with respect to the patient's 3D anatomy and pre-operative 3D diagnostic scans using intraoperative fluoroscopy for in situ registration and embedded fiducials. Preliminary studies have found a fiducial registration error (FRE) of 1.41 mm and a Target Localization Error (TLE) of 0.48 mm. The resulting system leverages equipment already commonly available in the operating room (OR), providing an important new functionality that is free of many current limitations, while keeping costs contained.

Artificial Intelligence↗

PubMed2000

In vitro micronucleus assay with Chinese hamster V79 cells - results of a collaborative study with in situ exposure to 26 chemical substances.

A collaborative study with 10 participating laboratories was conducted to evaluate a test protocol for the performance of the in vitro micronucleus (MN) test using the V79 cell line with one treatment and one sampling time only. A total of 26 coded substances were tested in this study for MN-inducing properties. Three substances were tested by all 10 laboratories and 23 substances were tested by three or four laboratories in parallel. Six aneugenic, 7 clastogenic and 6 non-genotoxic chemicals were uniformly recognised as such by all laboratories. Three chemicals were tested uniformly negative by three laboratories although also clastogenic properties have been reported for these substances. Another set of three clastogenic substances showed inconsistent results and one non-clastogenic substance was found to be positive by one out of three laboratories. Within the study, the applicability of the determination of a proliferation index (PI) as an internal cytotoxicity parameter in comparison with the determination of the mitotic index (MI) was also evaluated. Both parameters were found to be useful for the interpretation of the MN test result with regard to the control of cell cycle kinetics and the mode of action for MN induction. The MN test in vitro was found to be easy to perform and its results were mainly in accordance with results from chromosomal aberration tests in vitro.

Animals↗

PubMed2000

Three-dimensional computed tomographic reconstruction using a C-arm mounted XRII: image-based correction of gantry motion nonidealities.

The image quality of 3D reconstructions produced using a C-arm mounted XRII depends on precise determination of the geometric parameters that describe the detector system in the laboratory frame of reference. We have designed a simplified calibration system that depends on images of a metal sphere, acquired during rotation of the gantry through 200 degrees. Angle-dependent shift corrections are obtained, accounting for nonideal motion in two directions: perpendicular to the axis of rotation and tangential to the circular trajectory (tau), and parallel to the axis of rotation (xi). Projection images are corrected prior to reconstruction using a simple shift-interpolation algorithm. We show that the motion of the gantry is highly reproducible during acquisitions within one day (mean standard deviation in tau and xi is 0.11 mm and 0.08 mm, respectively), and over 21 months (mean standard deviation in tau and xi is 0.10 mm and 0.06 mm, respectively). Reconstruction of a small-bead phantom demonstrates uniformity of the correction algorithm over the full volume of the reconstruction [standard deviation of full-width-half-maximum of the beads is approximately 0.25 pixels (0.13 mm) over the volume of reconstruction]. Our approach provides a simple correction technique that can be applied when trajectory deviations are significant relative to the pixel size of the detector but small relative to the detector field of view, and when the fan angle of the acquisition geometry is small (<20 degrees). A comparison with other calibration techniques in the literature is provided.

Algorithms↗

PubMed2000

Prevention of adriamycin-induced mdr1 gene amplification and expression in mouse leukemia cells by simultaneous treatment with the anti-recombinogen bromovinyldeoxyuridine.

The anti-recombinogenic substance (E)-5-(2-bromovinyl)-2'-deoxyuridine (BVDU) was tested for its ability to prevent adriamycin-induced mdr1 gene amplification and expression in mouse leukemia cells in vitro. F4-6 cells that were treated with stepwise enhanced doses of adriamycin acquired resistance against adriamycin. While 20 ng/ml adriamycin showed strong toxic effects in sensitive cells, the same dose was tolerated at the end of the long-term experiment following treatment with stepwise enhanced doses of adriamycin. In parallel experiments, 0.5 or 1 microg/ml BVDU was given together with adriamycin. BVDU prevented the formation of resistance against adriamycin treatment. Using differential PCR, the signal intensity of the mdr1a-specific band appeared markedly increased in adriamycin-resistant cells, while the signal intensities of the adriamycin + BVDU-treated cells resembled the intensity ratio of the untreated control cells. Beyond that, in resistant F4-6 cells increased expression of mdr genes was demonstrated by Northern blot analysis.

Animals↗

PubMed1999

A three-dimensional cerebrovascular flow phantom.

We have constructed a life-sized fully three-dimensional (3D) rigid flow-through model of the cerebral vasculature. Average vessel diameters and lengths, taken from published values in the literature, were used to describe the geometry of our phantom; numerically controlled machining techniques were used to fabricate the model. Inflow to the phantom is provided through two internal carotid arteries and two vertebral arteries. Outflow is provided through the anterior cerebral arteries, the middle cerebral arteries, and the posterior cerebral arteries. The phantom includes the circle of Willis, and aneurysms of variable size may be attached at different locations. We have tested the model for geometric accuracy using high-resolution MR and CT imaging protocols, and have found that measured and prescribed diameters agree to within better than 4%. Flow dynamics, including waveform shape and flow division between branches, also mimic that seen in vivo, with flows within 16% (on average) of the prescribed values. We present 3D magnetic resonance angiography, digital subtraction angiography, and computed rotational angiography images of the phantom under conditions that mimic physiological situations.

Angiography, Digital Subtraction↗

PubMed1999

Adaptive resistance of Saccharomyces cerevisiae to chronic treatment with genotoxic and nongenotoxic carcinogens.

The exposure of mammalian cells or tumors for weeks or months to low nonlethal doses of cytostatic drugs may induce multidrug resistance, which can be enhanced by a variety of DNA-damaging agents. Multidrug resistance to a variety of drugs has been observed. But in yeast, DNA-damaging agents have not yet been tested. As the appearance of resistance is the result of longterm exposure, we decided to extend the application of test substances to a period of up to 400 days. In such long-term experiments S. cerevisiae MP1 adapted to treatment with low doses of mutagens. Consistent results were obtained for both genotoxic and nongenotoxic carcinogenic substances, which implies that there may be a single pathway for carcinogens with different modes of action.

Acetamides↗

PubMed1997

Reinvestigation of in vivo genotoxicity studies in man. I. No induction of DNA strand breaks in peripheral lymphocytes after metronidazole therapy.

Although a rodent carcinogen, metronidazole is widely used in humans for the treatment of infections with anaerobic organisms. Metronidazole is mutagenic for microorganisms, but has a mainly negative data base for mammals and humans. Therefore, metronidazole is generally considered as a non-genotoxic carcinogen. Only the results of two human in vivo studies would allow the classification of metronidazole as genotoxic carcinogen: (1) the induction of DNA strand breaks; and (2) the induction of chromosome aberrations in peripheral lymphocytes after metronidazole therapy. Because the classification of metronidazole as genotoxic carcinogen would imply enormous consequences with respect to its application, both studies were reinvestigated very thoroughly. The present report describes the reinvestigation of the induction of DNA strand breaks after metronidazole therapy. Each two probes of lymphocytes of metronidazole-treated patients (3 x 500 to 3 x 750 mg/day for 5-8 days) were examined separately for the appearance of DNA strand breaks before and after treatment. In total, 400 nuclei were examined per patient. Immediately before the first, and 30 min to 2 h after the last application, 2 x 10 ml blood per patient was sampled, transported to the laboratory at 15-20 degrees C to make DNA repair more difficult, and examined within the next 4-7 h for DNA strand breaks. At the same time, the individual metronidazole blood plasma levels were measured. In contrast to the published reports, no induction of DNA strand breaks after metronidazole therapy could be observed in the present study. As the applied doses (15,750 mg vs. 4800 mg) and the plasma level (up to 25 micrograms/ml vs. not measured) of metronidazole were much higher than in the published study, the relevance of the clearly negative result is obvious. As induction of DNA strand breaks is a frequent prerequisite for genotoxicity, metronidazole should be considered as a non-genotoxic carcinogen, and not as a genotoxic carcinogen.

Adult↗

PubMed1997

Three-dimensional computed tomographic reconstruction using a C-arm mounted XRII: correction of image intensifier distortion.

X-ray image intensifiers (XRIIs) have many applications in diagnostic imaging including acquisition of near-real-time projection images of the intracranial and coronary vasculature. Recently, there has been some interest in using this projection data to generate three-dimensional (3-D) computed tomographic (CT) reconstructions. The XRII and x-ray tube are rotated around the object, acquiring sufficient data for the simultaneous reconstruction of many transverse slices. Three-dimensional reconstructions are compromised, however, if the projection data is geometrically distorted in any way. Previous studies have shown the distortion in XRIIs to be substantial and to be highly angular dependent. In this paper, we present a global correction technique which provides a table of correction coefficients for an image acquired at any arbitrary angle about the patient. The coefficients are generated using a linear least-squares fit between the detected and known locations of a grid of small steel beads which is attached to the XRII (27 cm nominal diameter). We have performed corrections on 100 images obtained during rotation of the gantry through 200 degrees and find that a fifth-order polynomial provides optimum image distortion reduction (mean residual distortion of 0.07 pixels), however, fourth-order polynomials provide sufficient distortion reduction for our application (mean residual displacement of 0.1 pixels). Using sixth-order polynomials does not provide a statistically significant reduction in image distortion. The spatial distribution of residual distortion did not demonstrate any particular pattern over the face of the XRII. Image angle and coefficient angle must be known to within +/- 2 degrees in order to keep the mean residual distortion be approximately 0.5 pixels.

Humans↗

PubMed1997

Use of a C-arm system to generate true three-dimensional computed rotational angiograms: preliminary in vitro and in vivo results.

PURPOSE: To evaluate the potential use of a C-arm mounted X-ray image intensifier (XRII) system to generate three-dimensional computed rotational angiograms during interventional neuroradiologic procedures. METHODS: A clinical angiographic system was modified to allow collection of sufficient views during selective intraarterial contrast injections for CT reconstruction of a 15 x 15 x 15-cm3 volume. Image intensifier distortion and C-arm instabilities were corrected by using image-based techniques. The impact of the pulsatile nature of the vessels during image data acquisition and of the presence of bone on the 3-D reconstructions was investigated by generating 3-D reconstructions of an anesthetized 20-kg pig and of a human skull phantom. RESULTS: A sequence of images sufficient for 3-D reconstruction was acquired in less than 5 seconds. Image intensifier distortion and C-arm instabilities were corrected to subpixel accuracy (0.035 mm and 0.07 mm, respectively). Both the intracranial vessels of the pig and the small, high-contrast structures in the skull were reconstructed with negligible artifacts. CONCLUSIONS: Using a C-arm mounted XRII system, computed rotational angiography can provide true 3-D images of diagnostic quality.

Animals↗

PubMed1996

Anti-recombinogenic and convertible co-mutagenic effects of (E)-5-(2-bromovinyl)-2'-deoxyuridine (BVDU) and other 5-substituted pyrimidine nucleoside analogs in S. cerevisiae MP1.

In experiments using yeast, without addition of an external metabolic activation system, (E)-5-(2-bromovinyl)-2'-deoxyuridine (BVDU) was co-mutagenic and showed an insignificant anti-recombinogenic effect in combination with triethylene melamine (TEM). In the presence of activating S9-mix, the anti-recombinogenicity and co-mutagenicity could clearly be seen. At higher concentrations the co-mutagenic effect was converted into anti-mutagenicity. The other three 5-substituted pyrimidine nucleoside analogs were tested only in the presence of activating S9-mix and showed similar effects. As TEM is a direct alkylating agent that is inactivated by liver microsomes, the higher activity in presence of S9-mix can be interpreted as resulting from metabolic activation of the 5-substituted pyrimidine nucleoside analogs. In previous experiments using yeast bacteria, Drosophila or mice, tumor promoters were co-recombinogenic/anti-mutagenic, and co-carcinogens were co-mutagenic/anti-recombinogenic. Thus, there is not only an operational difference between tumor promoters and co-carcinogens but a real difference in respect to their genetic effectiveness. As up to now only co-carcinogens have shown co-mutagenic and anti-recombinogenic effects, it is perhaps possible that, within a certain concentration range, 5-substituted pyrimidine nucleoside analogs may have co-carcinogenic activity in carcinogenicity tests. At higher concentrations the co-carcinogenic effect may be converted into an anti-carcinogenic one.

Animals↗

PubMed1996

Induction or suppression of SV40 amplification by genotoxic carcinogens, non-genotoxic carcinogens or tumor promoters.

Carcinogens are generally classified into two groups: genotoxic and non-genotoxic. As the final product of genotoxic and non-genotoxic carcinogens is the same, i.e., a clone of genetically altered cells, it could be possible that non-genotoxic carcinogens may yield genotoxic events as a secondary result of cell toxicity having led to mitogenesis/cellular proliferation, or that genetic alterations are induced that are normally neglected in genotoxicity tests. A genetic effect with possible relevance for the ultimate mechanism of carcinogenicity is the amplification of oncogenes. In the present experiments, amplification of SV40-virus DNA in transformed CO631-cells has been measured. In this system, two genotoxic carcinogens (positive control), two non-carcinogens (negative control), and eight non-genotoxic carcinogens have been tested. With the exception of testosterone and BVDU, all substances were tested when given alone. Testosterone and BVDU were tested in combination with either MTX or AMP in the presence or absence of S9-mix. The genotoxic carcinogens TEM and 4-NQO as well as the tumor promoters TPA, coumarin, mezerein and chrysarobin were able to induce SV40 amplification when given alone. The same was for acetamide and thioacetamide. The non-carcinogens acetone and dimethylformamide were ineffective. In case of testosterone, a co-amplification effect was seen in the absence of S9-mix, and an anti-amplification effect in presence of S9-mix. The anti-recombinogen BVDU reduced the SV40 amplification effect of AMP in experiments without addition of S9-mix. In the presence of activating S9-mix, this substance was effective at lower concentrations than without S9-mix, and showed an enhanced anti-amplification effect. Similar effects of testosterone and BVDU had been observed before in respect to stimulation or suppression of recombination. These results can be used as supportive evidence for the assumption that gene amplification is mechanistically related to recombination.

Acetamides↗

PubMed1996

Co-recombinogenic and anti-mutagenic effects of diethylhexylphthalate, inactiveness of pentachlorophenol in the spot test with mice.

In in vivo experiments using the spot test with mice, diethylhexylphthalate (DEHP) was co-recombinogenic and anti-mutagenic. In two independent experiments, DEHP was able to increase in combination with ethylnitrosourea (ENU) the frequency of animals with spots of genetic relevance from about 12% (ENU alone) to about 15% (ENU+DEHP). This enhancement can be exclusively attributed to an enhancement of recombination. In historical as well as in current experiments, with astonishing accuracy, about 8% of all spots induced with ENU alone are black, near-white or twin spots, i.e., presumed products of reciprocal recombination. Under the influence of DEHP, about 20% of all colored spots were black, near-white or twin spots. These co-recombinogenic effects are very strong, considering that the low frequency of twin spots with 0.3% (historical ENU control) or 0.6% (current ENU control) after ENU treatment alone has been enhanced up to a frequency of 3%. While ENU alone induces about 14% light brown colored spots, depending exclusively on gene mutations, under the influence of DEHP the frequency was only 7%, i.e., DEHP was anti-mutagenic. Pentachlorophenol was ineffective in enhancing or reducing recombination or mutations. There was no difference between ENU and ENU+PCP treatment. Since a number of "non-genotoxic' carcinogens with tumor-promoting activities like D-limonene, 12-O-tetradecanoyl-phorbol-13-acetate (TPA) and 2,3,7,8-tetrachloro-dibenzo-p-dioxin (TCDD) have shown similar effects in the spot test, it is suggested that DEHP may have tumor-promoting activity in carcinogenicity tests.

Animals↗

PubMed1996

Anti-mutagenic agents are also co-recombinogenic and can be converted into co-mutagens.

In experiments using yeast without an external metabolic activation system, the hormones testosterone, beta-estradiol, and diethylstilbestrol were anti-mutagenic and co-recombinogenic. In the presence of Aroclor-induced rat liver S-9 plus cofactors (S9-mix) the same substances acted as co-mutagens and anti-recombinogens. Since an external metabolic activation system was able to convert anti-mutagens into co-mutagens, we studied whether the different metabolism of yeast and mice would lead to different effects. In whole-animal experiments using the mouse spot test, anti-mutagenic effects of vanillin (Imanishi et al., 1990), phenobarbital (Shibuya and Murota, 1984), and tannic acid (Sasaki et al., 1990) have been observed. In our present experiments with yeast, tannic acid and phenobarbital showed anti-mutagenic effects also, whereas vanillin acted as a co-mutagen. Thus, as in the case of the hormones, tannic acid and phenobarbital were anti-mutagenic and co-recombinogenic whereas vanillin was co-mutagenic as well as co-recombinogenic.

9,10-Dimethyl-1,2-benzanthracene↗