STEAM-sequence with multi-echo-readout for static magnetic resonance elastography

In static magnetic resonance elastography, the elasticity of an object is determined by measuring the internal displacement between two compression states. To reduce signal loss during the long time delay between application of external deformation and the static compression state, a STEAM sequence with a long mixing time is used This results in long scan times. The aim of this work was the development of a STEAM sequence with a multi-echo-readout, which allows the reduction of scan time and number of necessary external deformations. This new sequence was compared to the standard STEAM sequence on an agarose gel phantom with a hard inclusion. In addition, the elasticity of thermal tissue lesions was investigated, which were induced using high-intensity focused ultrasound (HIFU). During a given measurement time, more acquisitions per image can be taken using the multi-echo-readout. As a result the signal-to-noise ratio is increased and errors in the data become clearly smaller. Drawbacks of. the new sequence are its higher signal loss due to T2-decay and its greater sensitivity against ghosting artefacts caused by k-space segmentation. During the investigation of the thermally-induced lesions, a clear contrast in elasticity between normal tissue and the treated region was observed. Taking advantage of the greater accuracy of the new STEAM sequence, it was shown, that this contrast is significantly larger than the one in conventional MR parameters.     

MRI-guided surgery with high intensity focused ultrasound

High-intensity focused ultrasound allows high-precision, non-invasive thermocoagulation of tissues within seconds, with sparing of surrounding areas. The resulting tissue necrosis is so sharply demarcated that the technique is also defined focused ultrasound surgery (FUS). The combination with magnetic resonance imaging (MRI) allows an exact definition of the target volume and a safe guidance of FUS. The present paper describes the physical equipment necessary to perform MRI-guided FUS, and reports an example of application of this technique for the therapy of breast cancer. Finally, the paper outlines further examples of FUS application and future perspectives.     

Intracellular visualization of prostate cancer using magnetic resonance imaging

The term "molecular imaging" can be broadly defined as the in vivo characterization and measurement of biological processes at the cellular and molecular level. Is a gene expression magnetic resonance imaging (MRI) possible? Therefore, we have developed a novel intravital and intracellular MRI contrast agent composed of a gadolinium complex, an oligonucleotide sequence [peptide nucleic acid (PNA)], and a transmembrane carrier peptide that is composed of a peptide sequence similar to that of the homeodomain of the Antennapedia protein. The goal of our study was to determine whether this contrast agent could be accumulated in tumor cells in vitro (HeLa cells) and in vivo (Dunning R3327 AT1 rat prostate adenocarcinoma) and whether the specificity of the PNA for the up-regulated c-myc mRNA in the cell's cytoplasm would have an effect on contrast agent retention in the tumor cells. Using the c-myc-specific and a c-myc-nonspecific control PNA, an increase in signal intensity in the tumor cells was observed after 10 min in vitro and in vivo (maximum was reached in HeLa cells in vitro in 60 min, in Dunning R3327 AT1 rat prostate adenocarcinoma cells in vivo in 30 min). This increase of signal intensity could be maintained in vitro in HeLa cells for only 4 h and in Dunning R3327 AT1 rat prostate adenocarcinoma cells in vivo at least for 5 h by using the c-myc mRNA-specific PNA as a "retention" agent.     

Tachyphylaxis to inhaled isoproterenol and the effect of methylprednisolone in dogs

Acute tachyphylaxis can be induced to inhaled isoproterenol (ISO) in anesthetized, closed-chested mongrel dogs. The responsiveness to ISO measured as the percent reduction in methacholine-induced bronchoconstriction was decreased significantly (p less than 0.01) after a 1-hr period of repeated ISO inhalations (ISO-loading). Intravenous administration of methylprednisolone (1 mg/kg) reversed the decrease in responsiveness to ISO.     

Clonal Expansion of Staphylococcus epidermidis Strains Causing Hickman Catheter-Related Infections in a Hemato-Oncologic Department

The detailed analysis of 411 strains of coagulase-negative staphylococci (CoNS) obtained from 40 neutropenic hemato-oncologic patients (61 Hickman catheter episodes) on intensive chemotherapy is described. By random amplification of polymorphic DNA (RAPD) analysis, a total of 88 different genotypes were detected: 51 in air samples and 30 in skin cultures prior to insertion, 12 in blood cultures after insertion, and only 5 involved in catheter-related infections (CRI). Two RAPD genotypes of Staphylococcus epidermidis predominated, and their prevalence increased during patient hospitalization. At insertion, these clones constituted 11 of 86 (13%) CoNS isolated from air samples and 33 of 75 (44%) CoNS isolated from skin cultures. After insertion, their combined prevalence increased to 33 of 62 (53%) in catheters not associated with CRI and 139 of 188 (74%) in catheters associated with CRI (P = 0.0041). These two predominant S. epidermidis clones gave rise to a very high incidence of CRI (6.0 per 1,000 catheter days) and a very high catheter removal rate for CRI, 70%, despite prompt treatment with vancomycin. A likely source of S. epidermidis strains involved in CRI appeared to be the skin flora in 75% of cases. The validity of these observations was confirmed by pulsed-field gel electrophoresis (PFGE) of SmaI DNA macrorestriction fragments of blood culture CoNS isolates. Again, two predominant CoNS genotypes were found (combined prevalence, 60%). RAPD and PFGE yielded concordant results in 75% of cases. Retrospectively, the same two predominant CoNS clones were also found among blood culture CoNS isolates from the same hematology department in the period 1991 to 1993 (combined prevalence, 42%) but not in the period 1978 to 1982. These observations underscore the pathogenic potential of clonal CoNS types that have successfully and persistently colonized patients in this hemato-oncology department.     

Expression of CD44 in Apc and Tcf mutant mice implies regulation by the WNT pathway

Overexpression of cell surface glycoproteins of the CD44 family is an early event in the colorectal adenoma-carcinoma sequence. This suggests a link with disruption of APC tumor suppressor protein-mediated regulation of beta-catenin/Tcf-4 signaling, which is crucial in initiating tumorigenesis. To explore this hypothesis, we analyzed CD44 expression in the intestinal mucosa of mice and humans with genetic defects in either APC or Tcf-4, leading to constitutive activation or blockade of the beta-catenin/Tcf-4 pathway, respectively. We show that CD44 expression in the non-neoplastic intestinal mucosa of Apc mutant mice is confined to the crypt epithelium but that CD44 is strongly overexpressed in adenomas as well as in invasive carcinomas. This overexpression includes the standard part of the CD44 (CD44s) as well as variant exons (CD44v). Interestingly, deregulated CD44 expression is already present in aberrant crypt foci with dysplasia (ACFs), the earliest detectable lesions of colorectal neoplasia. Like ACFs of Apc-mutant mice, ACFs of familial adenomatous polyposis (FAP) patients also overexpress CD44. In sharp contrast, Tcf-4 mutant mice show a complete absence of CD44 in the epithelium of the small intestine. This loss of CD44 concurs with loss of stem cell characteristics, shared with adenoma cells. Our results indicate that CD44 expression is part of a genetic program controlled by the beta-catenin/Tcf-4 signaling pathway and suggest a role for CD44 in the generation and turnover of epithelial cells.     

Childhood overgrowth in patients with common NF1 microdeletions

While growth retardation and short stature are well-known features of patients with classical neurofibromatosis type 1 (NF1), we found advanced height growth and accelerated carpal bone age in patients with an NF1 microdeletion. Our analysis is based on growth data of 21 patients with common 1.4/1.2 Mb microdeletions, including three patients with a Weaver-like appearance. Overgrowth was most evident in preschool children (2-6 years, n=10, P=0.02). We conclude that childhood overgrowth is part of the phenotypic spectrum in patients with the common 1.4/1.2 Mb NF1 microdeletions and assume that the chromosomal region comprised by the microdeletions contains a gene whose haploinsufficiency causes overgrowth.     

Infectious Complications of Radiologically Inserted Hickman Catheters in Patients with Hematologic Disorders

Purpose: To assess the incidence of infections and its influence on the survival of radiologically inserted Hickman catheters (HCs) in patients with hematologic disorders and to determine factors associated with premature HC removal. Methods: Survival and complications of 175 HCs in 115 patients were studied retrospectively. To describe the data the Kaplan-Meier method and the log-rank test were used, using the date of HC removal due to HC-related infection as endpoint. A stratified Cox regression model was used to determine explanatory factors. Results: Seventy (40%) HCs were removed prematurely because of proven or probable HC-related infections. The incidence of infection leading to HC removal was 4.78 per 1000 catheter-days for proven HC infections. Univariate analysis revealed that acute myeloid leukemia, acute lymphocytic leukemia, or treatment for these diseases, gender, each subsequent catheter in the same patient and insertion site increased the risk of premature removal of the catheter due to infection. Conclusion: Infection is a major problem in patients with HCs. Unfortunately, the factors associated with increased infection rates that were found in this study cannot be influenced. Further studies are necessary to determine the role of environmental conditions in a radiology suite in relation to the risk of developing a catheter-related infection.