Genitourinary applications of diffusion-weighted MR imaging in the pelvis

Diffusion-weighted (DW) magnetic resonance (MR) imaging has a large number of potential clinical applications in the female and male pelvis and can easily be added to any routine MR protocol. In the female pelvis, DW imaging allows improvement of staging in endometrial and cervical cancer, especially in locally advanced disease and in patients in whom contrast medium administration should be avoided. It can also be helpful in characterizing complex adnexal masses and in depicting recurrent tumor after treatment of various gynecologic malignancies. DW imaging shows promising results in monitoring treatment response in patients undergoing radiation therapy of cervical cancer. An increase in apparent diffusion coefficient (ADC) values of responders precedes changes in size and may therefore allow early assessment of treatment success. In the male pelvis, the detection of prostate cancer in the peripheral zone is relatively easier than in the central gland based on the underlying ADC values, whereas overlapping values reported in the central gland still need further research. DW imaging might also be applied in the noninvasive evaluation of bladder cancer to differentiate between superficial and muscle-invasive tumors. Initial promising results have been reported in differentiating benign from malignant pelvic lymph nodes based on the ADC values; however, larger-scale studies will be needed to allow the detection of lymph node metastases in an individual patient. Prerequisites for successfully performing DW imaging of the female and male pelvis are standardization of the DW imaging technique, including the choice of b values, administration of an antiperistaltic drug, and comparison of DW findings with those of morphologic MR imaging.

Diffusion-weighted MR imaging in the head and neck

Extracranial applications of diffusion-weighted (DW) magnetic resonance (MR) imaging are gaining increasing importance, including in head and neck radiology. The main indications for performing DW imaging in this relatively small but challenging region of the body are tissue characterization, nodal staging, therapy monitoring, and early detection of treatment failure by differentiating recurrence from posttherapeutic changes. Lower apparent diffusion coefficients (ADCs) have been reported in the head and neck region of adults and children for most malignant lesions, as compared with ADCs of benign lesions. For nodal staging, DW imaging has shown promise in helping detect lymph node metastases, even in small (subcentimeter) nodes with lower ADCs, as compared with normal or reactive nodes. Follow-up of early response to treatment is reflected in an ADC increase in the primary tumor and nodal metastases; whereas nonresponding lesions tend to reveal only a slight increase or even a decrease in ADC during follow-up. Optimization and standardization of DW imaging technical parameters, comparison of DW images with morphologic images, and increasing experience, however, are prerequisites for successful application of this challenging technique in the evaluation of various head and neck pathologic conditions.

Standardization of infusion solutions to reduce the risk of incompatibility

PURPOSE: Although critically ill patients usually have various central intravenous (i.v.) lines, numerous drugs have to be infused simultaneously through the same lines. This can result in potentially harmful in-line incompatibility that can cause decreased drug effectiveness or increased microparticle load. To minimize the risk of these medication errors at an anesthesia intensive care unit (ICU), the preparation and administration of continuously infused drugs were standardized and the practicability in daily clinical routine was evaluated. SUMMARY: The concentration and diluent of continuously administered i.v. drugs were standardized. The drugs were grouped according to pH, medical indication, and chemical structure. The ICU staff decided to use multilumen central venous catheters, and each group of drugs was assigned to one lumen. Only drugs that belonged to the same group were infused simultaneously through the same lumen; therefore, intragroup incompatibilities had to be excluded before establishing the new drug administration plan at the ICU. The visual compatibility of 115 clinically reasonable intragroup drug mixtures was investigated. All drug combinations were compatible for six hours except mixtures containing thiopental, which was reassigned to a single-line use. In the following year, the practicability of this drug administration plan was evaluated. No deviations were found in the compliance of the staff prescribing and preparing only standardized concentrations and diluents. Further research to investigate the chemical compatibility of the drugs in these multiple mixtures will follow. CONCLUSION: A project intended to avoid incompatibility among i.v. drugs infused in the intensive care setting included steps to standardize solutions and determine which could be given together.

The European baseline series in 10 European Countries, 2005/2006--results of the European Surveillance System on Contact Allergies (ESSCA)

BACKGROUND: Continual surveillance based on patch test results has proved useful for the identification of contact allergy. OBJECTIVES: To provide a current view on the spectrum of contact allergy to important sensitizers across Europe. PATIENTS/METHODS: Clinical and patch test data of 19 793 patients patch tested in 2005/2006 in the 31 participating departments from 10 European countries (the European Surveillance System on Contact Allergies' (ESSCA) www.essca-dc.org) were descriptively analysed, aggregated to four European regions. RESULTS: Nickel sulfate remains the most common allergen with standardized prevalences ranging from 19.7% (central Europe) to 24.4% (southern Europe). While a number of allergens shows limited variation across the four regions, such as Myroxylon pereirae (5.3-6.8%), cobalt chloride (6.2-8.8%) or thiuram mix (1.7-2.4%), the differences observed with other allergens may hint on underlying differences in exposures, for example: dichromate 2.4% in the UK (west) versus 4.5-5.9% in the remaining EU regions, methylchloroisothiazolinone/methylisothiazolinone 4.1% in the South versus 2.1-2.7% in the remaining regions. CONCLUSIONS: Notwithstanding residual methodological variation (affecting at least some 'difficult' allergens) tackled by ongoing efforts for standardization, a comparative analysis as presented provides (i) a broad overview on contact allergy frequencies and (ii) interesting starting points for further, in-depth investigation.

The CONSORT statement checklist in allergen-specific immunotherapy: a GA2LEN paper

The methodology of randomized clinical trials is essential for the critical assessment and registration of therapeutic interventions. The CONSORT (Consolidated Standards of Reporting Trials) statement was developed to alleviate the problems arising from the inadequate reporting of randomized controlled trials. The present article reflects on the items that we believe should be included in the CONSORT checklist in the context of conducting and reporting trials in allergen-specific immunotherapy. Only randomized, blinded (in particular blinding of patients, health care providers, and outcome assessors), placebo-controlled Phase III studies in this article. Our analysis focuses on the definition of patients' inclusion and exclusion criteria, allergen standardization, primary, secondary and exploratory outcomes, reporting of adverse events and analysis.

Integrated data acquisition and processing to determine metabolite contents, relaxation times, and macromolecule baseline in single examinations of individual subjects

Absolute quantitation of clinical (1)H-MR spectra is virtually always incomplete for single subjects because the separate determination of spectrum, baseline, and transverse and longitudinal relaxation times in single subjects is prohibitively long. Integrated Processing and Acquisition of Data (IPAD) based on a combined 2-dimensional experimental and fitting strategy is suggested to substantially improve the information content from a given measurement time. A series of localized saturation-recovery spectra was recorded and combined with 2-dimensional prior-knowledge fitting to simultaneously determine metabolite T(1) (from analysis of the saturation-recovery time course), metabolite T(2) (from lineshape analysis based on metabolite and water peak shapes), macromolecular baseline (based on T(1) differences and analysis of the saturation-recovery time course), and metabolite concentrations (using prior knowledge fitting and conventional procedures of absolute standardization). The procedure was tested on metabolite solutions and applied in 25 subjects (15-78 years old). Metabolite content was comparable to previously found values. Interindividual variation was larger than intraindividual variation in repeated spectra for metabolite content as well as for some relaxation times. Relaxation times were different for various metabolite groups. Parts of the interindividual variation could be explained by significant age dependence of relaxation times.

[Navigation and robotics of the lateral skull base]

Computer-aided microscopic surgery of the lateral skull base is a rare intervention in daily practice. It is often a delicate and difficult minimally invasive intervention, since orientation between the petrous bone and the petrous bone apex is often challenging. In the case of aural atresia or tumors the normal anatomical landmarks are often absent, making orientation more difficult. Navigation support, together with imaging techniques such as CT, MR and angiography, enable the surgeon in such cases to perform the operation more accurately and, in some cases, also in a shorter time. However, there are no internationally standardised indications for navigated surgery on the lateral skull base. Miniaturised robotic systems are still in the initial validation phase.

Expression, purification, and projection structure by single particle electron microscopy of functional human TRPM4 heterologously expressed in Xenopus laevis oocytes

Despite efforts implicating the cationic channel transient receptor potential melastatin member 4 (TRPM4) to cardiac, nervous, and immunological pathologies, little is known about its structure and function. In this study, we optimized the requirements for purification and extraction of functional human TRPM4 protein and investigated its supra-molecular assembly. We selected the Xenopus laevis oocyte expression system because it lacks endogenous TRPM4 expression, it is known to overexpress functional human membrane channels, can be used for structure-function analysis within the same system, and is easily scaled to improve yield and develop moderate throughput capabilities through the use of robotics. Negative-stain electron microscopy (EM) revealed various sized low-resolution particles. Single particle analysis identified the majority of the projections represented the monomeric form with additional oligomeric structures potentially characterized as tetramers. Two-electrode voltage clamp electrophysiology demonstrated that human TRPM4 is functionally expressed at the oocyte plasma membrane. This study opens the door for medium-throughput screening and structure-function determination of this important therapeutically relevant target.

Clinical Proton MR Spectroscopy in Central Nervous System Disorders.

A large body of published work shows that proton (hydrogen 1 [(1)H]) magnetic resonance (MR) spectroscopy has evolved from a research tool into a clinical neuroimaging modality. Herein, the authors present a summary of brain disorders in which MR spectroscopy has an impact on patient management, together with a critical consideration of common data acquisition and processing procedures. The article documents the impact of (1)H MR spectroscopy in the clinical evaluation of disorders of the central nervous system. The clinical usefulness of (1)H MR spectroscopy has been established for brain neoplasms, neonatal and pediatric disorders (hypoxia-ischemia, inherited metabolic diseases, and traumatic brain injury), demyelinating disorders, and infectious brain lesions. The growing list of disorders for which (1)H MR spectroscopy may contribute to patient management extends to neurodegenerative diseases, epilepsy, and stroke. To facilitate expanded clinical acceptance and standardization of MR spectroscopy methodology, guidelines are provided for data acquisition and analysis, quality assessment, and interpretation. Finally, the authors offer recommendations to expedite the use of robust MR spectroscopy methodology in the clinical setting, including incorporation of technical advances on clinical units. © RSNA, 2014 Online supplemental material is available for this article.

Novel biomarkers for the prediction of metastasis in colorectal cancer

INTRODUCTION In patients with metastatic colorectal cancers, multimodal management and the use of biological agents such as monoclonal antibodies have had major positive effects on survival. The ability to predict which patients may be at 'high risk' of distant metastasis could have major implications on patient management. Histomorphological, immunohistochemical or molecular biomarkers are currently being investigated in order to test their potential value as predictors of metastasis. AREAS COVERED Here, the author reviews the clinical and functional data supporting the investigation of three novel promising biomarkers for the prediction of metastasis in patients with colorectal cancer: tumor budding, Raf1 kinase inhibitor protein (RKIP) and metastasis-associated in colon cancer-1 (MACC1). EXPERT OPINION The lifespan of most potential biomarkers is short as evidenced by the rare cases that have successfully made their way into daily practice such as KRAS or microsatellite instability (MSI) status. Although the three biomarkers reviewed herein have the potential to become important predictive biomarkers of metastasis, they have similar hurdles to overcome before they can be implemented into clinical management: standardization and validation in prospective patient cohorts.

Precipitation over the past four centuries in the Dieshan Mountains as inferred from tree rings: An introduction to an HHT-based method

To improve our understanding of the Asian monsoon system, we developed a hydroclimate reconstruction in a marginal monsoon shoulder region for the period prior to the industrial era. Here, we present the first moisture sensitive tree-ring chronology, spanning 501 years for the Dieshan Mountain area, a boundary region of the Asian summer monsoon in the northeastern Tibetan Plateau. This reconstruction was derived from 101 cores of 68 old-growth Chinese pine (Pinus tabulaeformis) trees. We introduce a Hilbert–Huang Transform (HHT) based standardization method to develop the tree-ring chronology, which has the advantages of excluding non-climatic disturbances in individual tree-ring series. Based on the reliable portion of the chronology, we reconstructed the annual (prior July to current June) precipitation history since 1637 for the Dieshan Mountain area and were able to explain 41.3% of the variance. The extremely dry years in this reconstruction were also found in historical documents and are also associated with El Niño episodes. Dry periods were reconstructed for 1718–1725, 1766–1770 and 1920–1933, whereas 1782–1788 and 1979–1985 were wet periods. The spatial signatures of these events were supported by data from other marginal regions of the Asian summer monsoon. Over the past four centuries, out-of-phase relationships between hydroclimate variations in the Dieshan Mountain area and far western Mongolia were observed during the 1718–1725 and 1766–1770 dry periods and the 1979–1985 wet period.