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Biomedical subjects

Frank Sauer

Publications and source records attributed to Frank Sauer.

14 recordsLinked to original sources

Augmented reality visualization for CT-guided interventions: system description, feasibility, and initial evaluation in an abdominal phantom.

UNLABELLED: The purpose of this study was to evaluate the feasibility and performance of an augmented reality (AR) visualization prototype for virtual computed tomography (CT)-guided interventional procedures in a multimodality abdominal phantom. With the aid of AR guidance, three radiologists performed 30 attempts at targeting simulated liver lesions of different sizes (range, 5-15 mm) with a biopsy needle. The position of the needle tip relative to the lesion was verified by using ultrasonography and CT. With AR guidance, lesions were successfully targeted with the first needle pass in all cases. On the basis of these results, AR visualization for CT-guided intervention appears feasible and allows intuitive and accurate lesion targeting in a phantom. SUPPLEMENTAL MATERIAL: radiology.rsnajnls.org/cgi/content/full/2401040018/DC1

Abdomen↗

RETRACTED: Noncoding RNAs of trithorax response elements recruit Drosophila Ash1 to Ultrabithorax.

Homeotic genes contain cis-regulatory trithorax response elements (TREs) that are targeted by epigenetic activators and transcribed in a tissue-specific manner. We show that the transcripts of three TREs located in the Drosophila homeotic gene Ultrabithorax (Ubx) mediate transcription activation by recruiting the epigenetic regulator Ash1 to the template TREs. TRE transcription coincides with Ubx transcription and recruitment of Ash1 to TREs in Drosophila. The SET domain of Ash1 binds all three TRE transcripts, with each TRE transcript hybridizing with and recruiting Ash1 only to the corresponding TRE in chromatin. Transgenic transcription of TRE transcripts restores recruitment of Ash1 to Ubx TREs and restores Ubx expression in Drosophila cells and tissues that lack endogenous TRE transcripts. Small interfering RNA-induced degradation of TRE transcripts attenuates Ash1 recruitment to TREs and Ubx expression, which suggests that noncoding TRE transcripts play an important role in epigenetic activation of gene expression.

Amino Acid Motifs↗

An augmented reality system for MR image-guided needle biopsy: initial results in a swine model.

PURPOSE: To evaluate an augmented reality (AR) system in combination with a 1.5-T closed-bore magnetic resonance (MR) imager as a navigation tool for needle biopsies. MATERIALS AND METHODS: The experimental protocol had institutional animal care and use committee approval. Seventy biopsies were performed in phantoms by using 20 tube targets, each with a diameter of 6 mm, and 50 virtual targets. The position of the needle tip in AR and MR space was compared in multiple imaging planes, and virtual and real needle tip localization errors were calculated. Ten AR-guided biopsies were performed in three pigs, and the duration of each procedure was determined. After successful puncture, the distance to the target was measured on MR images. The confidence limits for the achieved in-plane hit rate and for lateral deviation were calculated. A repeated measures analysis of variance was used to determine whether the placement error in a particular dimension (x, y, or z) differed from the others. RESULTS: For the 50 virtual targets, a mean error of 1.1 mm +/- 0.5 (standard deviation) was calculated. A repeated measures analysis of variance indicated no statistically significant difference (P > .99) in the errors in any particular orientation. For the real targets, all punctures were inside the 6-mm-diameter tube in the transverse plane. The needle depth was within the target plane in 11 biopsy procedures; the mean distance to the center of the target was 2.55 mm (95% confidence interval: 1.77 mm, 3.34 mm). For nine biopsy procedures, the needle tip was outside the target plane, with a mean distance to the edge of the target plane of 1.5 mm (range, 0.07-3.46 mm). In the animal experiments, the puncture was successful in all 10 cases, with a mean target-needle distance of 9.6 mm +/- 4.85. The average procedure time was 18 minutes per puncture. CONCLUSION: Biopsy procedures performed with a combination of a closed-bore MR system and an AR system are feasible and accurate.

Animals↗

Automatic registration of portal images and volumetric CT for patient positioning in radiation therapy.

The efficacy of radiation therapy treatment depends on the patient setup accuracy at each daily fraction. A significant problem is reproducing the patient position during treatment planning for every fraction of the treatment process. We propose and evaluate an intensity based automatic registration method using multiple portal images and the pre-treatment CT volume. We perform both geometric and radiometric calibrations to generate high quality digitally reconstructed radiographs (DRRs) that can be compared against portal images acquired right before treatment dose delivery. We use a graphics processing unit (GPU) to generate the DRRs in order to gain computational efficiency. We also perform a comparative study on various similarity measures and optimization procedures. Simple similarity measure such as local normalized correlation (LNC) performs best as long as the radiometric calibration is carefully done. Using the proposed method, we achieved better than 1mm average error in repositioning accuracy for a series of phantom studies using two open field (i.e., 41 cm2) portal images with 90 degrees vergence angle.

Algorithms↗

Learning based non-rigid multi-modal image registration using Kullback-Leibler divergence.

The need for non-rigid multi-modal registration is becoming increasingly common for many clinical applications. To date, however, existing proposed techniques remain as largely academic research effort with very few methods being validated for clinical product use. It has been suggested by Crum et al. that the context-free nature of these methods is one of the main limitations and that moving towards context-specific methods by incorporating prior knowledge of the underlying registration problem is necessary to achieve registration results that are accurate and robust enough for clinical applications. In this paper, we propose a novel non-rigid multi-modal registration method using a variational formulation that incorporates a prior learned joint intensity distribution. The registration is achieved by simultaneously minimizing the Kullback-Leibler divergence between an observed and a learned joint intensity distribution and maximizing the mutual information between reference and alignment images. We have applied our proposed method on both synthetic and real images with encouraging results.

Algorithms↗

A novel phantom-less spatial and temporal ultrasound calibration method.

This paper introduces a novel method for ultrasound calibration for both spatial and temporal parameters. The main advantage of this method is that it does not require a phantom, which is usually expensive to fabricate. Furthermore, the method does not require extensive image processing. For spatial calibration, we solve an optimization problem established by a set of equations that relate the orientations of a line (i.e., calibration pointer) to the intersection points appearing in the ultrasound image. The line orientation is provided through calibration of both ends of the calibration pointer. Temporal calibration is achieved by processing of the captured pointer orientations and the corresponding image positions of intersection along with the timing information. The effectiveness of the unified method for both spatial and temporal calibration is apparent from the quality of the 3D reconstructions of a known object.

Algorithms↗

Characterizing single suspended cells by optorheology.

The measurement of the mechanical properties of individual cells has received much attention in recent years. In this paper we describe the application of optically induced forces with an optical stretcher to perform step-stress experiments on individual suspended fibroblasts. The conversion from creep-compliance to frequency-dependent complex shear modulus reveals characteristic viscoelastic signatures of the underlying cytoskeleton and its dynamic molecular properties. Both normal and cancerous fibroblasts display a single stress relaxation time in the observed time and frequency space that can be related to the transient binding of actin crosslinking proteins. In addition, shear modulus and steady-state viscosity of the shell-like actin cortex as the main module resisting small deformations are extracted. These values in combination with insight into the cells' architecture are used to explain their different deformability. This difference can then be exploited to distinguish normal from cancerous cells. The nature of the optical stretcher as an optical trap allows easy incorporation in a microfluidic system with automatic trapping and alignment of the cells, and thus a high measurement throughput. This carries the potential for using the microfluidic optical stretcher to investigate cellular processes involving the cytoskeleton and to diagnose diseases related to cytoskeletal alterations.

Animals↗

RETRACTED: TAF1 activates transcription by phosphorylation of serine 33 in histone H2B.

Dynamic changes in chromatin structure, induced by posttranslational modification of histones, play a fundamental role in regulating eukaryotic transcription. Here we report that histone H2B is phosphorylated at evolutionarily conserved Ser33 (H2B-S33) by the carboxyl-terminal kinase domain (CTK) of the Drosophila TFIID subunit TAF1. Phosphorylation of H2B-S33 at the promoter of the cell cycle regulatory gene string and the segmentation gene giant coincides with transcriptional activation. Elimination of TAF1 CTK activity in Drosophila cells and embryos reduces transcriptional activation and phosphorylation of H2B-S33. These data reveal that H2B-S33 is a physiological substrate for the TAF1 CTK and that H2B-S33 phosphorylation is essential for transcriptional activation events that promote cell cycle progression and development.

Acetylation↗

An AR system with intuitive user interface for manipulation and visualization of 3D medical data.

We report on a stereoscopic video-see-through augmented reality system which we developed for medical applications. Our system allows interactive in-situ visualization of 3D medical imaging data. For high-quality rendering of the augmented scene we utilize the capabilities of the latest graphics card generations. Fast high-precision MPR generation ("multiplanar reconstruction") and volume rendering is realized with OpenGL 3D textures. We provide a tracked hand-held tool to interact with the medical imaging data in its actual location. This tool is represented as a virtual tool in the space of the medical data. The user can assign different functionality to it: select arbitrary MPR cross-sections, guide a local volume rendered cube through the medical data, change the transfer function, etc. Tracking works in conjunction with retroreflective markers, which frame the workspace for head tracking respectively are attached to instruments for tool tracking. We use a single head-mounted tracking camera, which is rigidly fixed to the stereo pair of cameras that provide the live video view of the real scene. The user's spatial perception is based on stereo depth cues as well as on the kinetic depth cues that he receives with the viewpoint variations and the interactive data visualization. The AR system has a compelling real-time performance with 30 stereo-frames/second and exhibits no time lag between the video images and the augmenting graphics. Thus, the physician can interactively explore the medical imaging information in-situ.

Diagnostic Imaging↗

An Augmented Reality system for MRI-guided needle biopsies.

A navigation system can increase the speed and accuracy of MR guided interventions that make use of scanners with high-field closed magnets. We report on first needle placement experiments performed with an Augmented Reality (AR) navigation system. AR visualization provides very intuitive guidance, resulting in a faster procedure. The accuracy of the needle placement depends on the registration accuracy of the system. In the present trials, the needle was placed as good as 1mm close to the target center, however in a small number of cases substantially larger errors occurred and were most likely caused by needle bending.

Biopsy, Needle↗

Histone methylation by the Drosophila epigenetic transcriptional regulator Ash1.

The establishment and maintenance of mitotic and meiotic stable (epigenetic) transcription patterns is fundamental for cell determination and function. Epigenetic regulation of transcription is mediated by epigenetic activators and repressors, and may require the establishment, 'spreading' and maintenance of epigenetic signals. Although these signals remain unclear, it has been proposed that chromatin structure and consequently post-translational modification of histones may have an important role in epigenetic gene expression. Here we show that the epigenetic activator Ash1 (ref. 5) is a multi-catalytic histone methyl-transferase (HMTase) that methylates lysine residues 4 and 9 in H3 and 20 in H4. Transcriptional activation by Ash1 coincides with methylation of these three lysine residues at the promoter of Ash1 target genes. The methylation pattern placed by Ash1 may serve as a binding surface for a chromatin remodelling complex containing the epigenetic activator Brahma (Brm), an ATPase, and inhibits the interaction of epigenetic repressors with chromatin. Chromatin immunoprecipitation indicates that epigenetic activation of Ultrabithorax transcription in Drosophila coincides with trivalent methylation by Ash1 and recruitment of Brm. Thus, histone methylation by Ash1 may provide a specific signal for the establishment of epigenetic, active transcription patterns.

Animals↗

In vitro assays to study protein ubiquitination in transcription.

Polyubiquitination is a death signal for proteins and condemns proteins to subsequent degradation by the 26S proteasome. However, recent studies imply that monoubiquitination and polyubiquitination of proteins do not necessarily result in protein degradation but play an important role in the execution of various biological events such as signal transduction and transcription. Ubiquitin was originally identified as a moiety attached to histones, and this as well as other histone modifications may play an important role for transcription and various other DNA-dependent processes. Considerable progress has been made in linking several histone modifications with chromatin dynamics in transcription. Acetylation of histones has been intimately linked to activation of transcription, while deacetylation is concomitant with repression of transcription. Although other histone modifications such as methylation, phosphorylation, and ubiquitination have been correlated with transcriptionally competent or inactive chromatin, the enzymes that mediate these modifications are only now being discovered. The identification of these histone-modifying enzymes may provide valuable insights into the role and function of histone modifications such as ubiquitination in transcription as well as other DNA-dependent processes. Recently, we have used various in vitro assays to show that the coactivator TAF(II)250 possesses both ubiquitin-activating and ubiquitin-conjugating activities, which monoubiquitinate histone H1. Here, we describe the methods used to identify this bifunctional enzyme: (1) in-gel activity assay; (2) protein-transfer membrane activity assay; and (3) in-solution activity assay. These methods have been successfully used to identify various histone-modifying enzymes and protein kinases. In this article we contribute a short review of the history of the methods used to study ubiquitination of proteins and histone modification. We provide protocols for in-gel, protein-transfer membrane, and in-solution ubiquitination assays. A discussion of the general use of the provided protocols, their limitations, and future perspectives are presented. The described methods provide useful tools for the identification of not only novel histone-modifying enzymes but also other protein-modifying enzymes that act in a variety of biological events.

Animals↗

An augmented reality system for ultrasound guided needle biopsies.

We have developed an augmented reality visualization system that helps the physician perform ultrasound guided needle biopsies. For a needle biopsy, the needle has to be inserted into an anatomical target to remove a tissue sample. Ultrasound guidance is routinely used e.g. for breast needle biopsies. The real-time ultrasound images allow the physician to locate the target and to monitor the needle position. Our system uses a combination of an optical laser guide and a virtual guide in the augmented image to provide intuitive guidance for the needle placement. There is no need to track the needle, i.e. there is no need to instrument the needle for tracking. In phantom tests, users have performed well with the system without prior training. This paper describes special features of our system and the workflow for the needle placement procedure.

Biopsy, Needle↗