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Biomedical subjects

Anne Richter

Publications and source records attributed to Anne Richter.

6 recordsLinked to original sources

Three-dimensional spatial modelling of the correlation between abdominal motion and lung tumour motion with breathing.

The aim of this research was to investigate whether a spatial correlation could be found between an external 3-D respiratory signal and the tumour trajectory. The respiratory signal was obtained by tracking the abdominal movement and the tumour trajectory was obtained by automatically determining the tumour position in a series of portal images. Three different models, based on Systems Identification, are presented to model the correlation using a 1-D respiratory signal, a 3-D respiratory signal and a 3-D respiratory signal together with previously determined tumour positions. Adequate correlation was found for all models in the direction of the tumour movement with standard deviations of 0.89 mm, 0.72 mm and 0.75 mm, respectively, and model fit of Rt2 = 0.19, 0.63 and 0.82, respectively. Increasing the frame rate for the acquisition of portal images from 3 to 15 frames per second improved the standard deviation and model fit. In summary, it is possible to spatially correlate a 3-D respiratory signal with the tumour trajectory using this approach. The models presented provide a framework that can be extended to include more information if required. A 3-D respiratory signal is preferable to a 1-D signal in modelling the tumour motion that is not along the main axis of tumour movement.

Abdomen↗

Tracking moving objects with megavoltage portal imaging: a feasibility study.

Four different algorithms were investigated with the aim to determine their suitability to track an object in conventional megavoltage portal images. The algorithms considered were the mean of the sum of squared differences (MSSD), mutual information (MI), the correlation ratio (CR), and the correlation coefficient (CC). Simulation studies were carried out with various image series containing a rigid object of interest that was moved along a predefined trajectory. For each of the series the signal-to-noise ratio (SNR) was varied to compare the performance of the algorithms under noisy conditions. For a poor SNR of -6 dB the mean tracking error was 2.4, 6.5, 39.0, and 17.2 pixels for MSSD, CC, CR and MI, respectively, with a standard deviation of 1.9, 12.9, 19.5, and 7.5 pixels, respectively. The size of a pixel was 0.5 mm. These results improved to 1.1, 1.3, 1.3, and 2.0 pixels, respectively, with a standard deviation of 0.6, 0.8, 0.8, and 2.1 pixels, respectively, when a mean filter was applied to the images prior to tracking. The implementation of MSSD into existing in-house software demonstrated that, depending on the search range, it was possible to process between 2 and 15 images/s, making this approach capable of real-time applications. In conclusion, the best geometric tracking accuracy overall was obtained with MSSD, followed by CC, CR, and MI. The simplest and best algorithm, both in terms of geometric accuracy as well as computational cost, was the MSSD algorithm and was therefore the method of choice.

Algorithms↗

Differential regulation of P-selectin ligand expression in naive versus memory CD4+ T cells: evidence for epigenetic regulation of involved glycosyltransferase genes.

Lymphocytes are targeted to inflamed sites by specific "homing" and chemokine receptors. Most of them, including ligands for P- and E-selectin, are absent from naive CD4(+) T cells and become induced after activation and differentiation in effector/memory cells. Polarized effector cells are characterized by the rapid production of distinct cytokines upon restimulation. Their cytokine memory is in part controlled by epigenetic imprinting during differentiation. Here we ask whether a similar mechanism could regulate selectin ligand expression, mediating entry into inflamed sites, notably within the skin. We report that acquisition of selectin ligands by naive but not memory CD4(+) cells depends on progression through the G(1)/S phase of the cell cycle-a phase susceptible to modification of the chromatin structure. Cell-cycle arrest prevented transcriptional activation of glycosyltransferases involved in the generation of selectin ligands, suggesting that progression through the cell cycle is required to unlock their genes. Artificial DNA demethylation strongly increased the frequency of selectin ligand-expressing cells, suggesting that DNA methylation keeps transferase genes inaccessible in naive T cells. Due to these findings we propose that selectin-dependent inflammation-seeking properties are imprinted by epigenetic modifications upon T-cell differentiation into effector cells.

Animals↗

Establishment of memory for IL-10 expression in developing T helper 2 cells requires repetitive IL-4 costimulation and does not impair proliferation.

T helper (Th) lymphocytes can develop memory for the expression of particular cytokines, like IL-4 or IL-10, in that reexpression of those cytokines is independent of the original costimulatory signal IL-4 and depends only on T cell receptor stimulation. Here, we show that in the course of Th2 cell differentiation in vitro, IL-4 memory is established during primary activation of naïve Th cells, whereas the establishment of IL-10 memory requires repetitive stimulation of the Th cell with IL-4 and T cell receptor. Likewise, established IL-10 memory, maintained in the absence of further IL-4 signals, was observed in individual IL-10-producing cells generated from in vivo antigen-experienced CD62L(low) Th cells and isolated by using the newly developed cytometric cytokine secretion assay for IL-10. In naïve Th cells undergoing primary activation, the induction of both IL-4 and IL-10 memory requires DNA synthesis, but reexpression of the cytokine genes can occur throughout cell cycle. In in vitro polarized Th2 cell populations, Th cells with IL-4 or IL-10 memory do not differ in proliferative behavior. Populations of Th cells isolated from polarized Th2 cultures according to expression of IL-4 or IL-10 also do not differ in proliferative behavior. Their proliferation mainly depends on IL-2. Thus, effector memory Th lymphocytes with memory for IL-4 or IL-10 expression are not intrinsically impaired in their proliferative potential and can play an essential role in reactive immunological memory and its regulation.

Animals↗

Cytokine memory of T helper lymphocytes.

Memory is one of the key features of the adaptive immune system. Specific T and B lymphocytes are primed for a particular antigen and upon challenge with it will react faster than naive lymphocytes. They also memorize the expression of key effector molecules, in particular cytokines, which determine the type and scale of an immune reaction. While in primary activations differential expression of cytokine genes is dependent on antigen-receptor signaling and differentiation signals, in later activations the expression is triggered by antigen-receptor signaling and dependent on the cytokine memory. The molecular basis of the cytokine memory implies differential expression of transcription factors and epigenetic modifications of cytokine genes and gene loci. GATA-3 for Th2 and T-bet for Th1 cells expressing interleukin-4 or interferon-gamma, respectively, are prime candidates for key transcription factors of cytokine memory. The essential role of epigenetic modifications is suggested by the requirement of DNA synthesis for the establishment of a cytokine memory in Th lymphocytes. At present the molecular link between transcription factors and epigenetic modifications of cytokine genes in the establishment and maintenance of cytokine memory is not clear. The initial cytokine memory is not stable against adverse differentiation signals, while in repeatedly stimulated lymphocytes it is stabilized by a variety of mechanisms.

Animals↗

Rapid-cycle improvement in quality of care for patients hospitalized with acute myocardial infarction or heart failure: moving from a culture of missed opportunity to a system of accountability.

We describe a 1-year multidisciplinary initiative to improve the quality of care for patients with acute myocardial infarction and heart failure. In January 2002, this rapid-cycle improvement project began with a partnership of inpatient cardiology nursing and physician leadership. This inpatient leadership team analyzed clinical and operational processes, and revised and developed tools such as standard order sets, discharge instructions, clinical pocket guides, and daily monitoring logs. Once the tools and processes, were implemented, the team began "daily monitoring" to assess tool use. At the same time, a process was implemented to provide rapid feedback on key quality indicator compliance within a short time after discharge. At 12 months, quality improvements have been demonstrated.

Hospitalization↗