Semi-quantitative Information Research Articles

Semi-quantitative determination of designer benzodiazepines in serum by adaption of an automated LC-MSn screening approach

Objectifs In 2012 benzodiazepine-type compounds started to extend the group of New Psychoactive Substances (NPS) sold on the internet as alleged legal recreational drugs. Initially, benzodiazepines like phenazepam and etizolam - which are still prescribed in some countries - were sold on the internet as recreational drugs. Subsequently, the group of so-called designer benzodiazepines was enlarged by compounds that either are active metabolites (e.g. norfludiazepam) or precursors (e.g. diclazepam) of known benzodiazepines or combine structural properties of different classical benzodiazepines (e.g. flubromazolam). Patents and scientific literature describe the synthesis and detailed results of animal model studies for more than a hundred different benzodiazepines, so it can be assumed that this sub-group of NPS will extend quickly in the future. The aim of this project was to develop an easy-to-use screening-method to detect and identify prescription and designer benzodiazepines and additionally obtain semi-quantitative information in a single run. Methods 1 mL serum sample was extracted using an established liquid-liquid extraction (LLE) protocol. Chromatographic separation was performed using a 13-minute formic acid/acetonitrile LC gradient and a Dionex Acclaim RLSC C18 100 × 2 mm column. An amaZon speed ion trap MS (Toxtyper ® , Bruker Daltonik) operating in ESI positive mode was used to generate MS2 and MS3 spectra according to a scheduled precursor list (SPL) triggered acquisition process. Compounds were identified by an in-house generated spectral library, containing retention time, MS and MS 2 /MS 3 information of currently 58 benzodiazepines. The linear range of the method was evaluated by fortifying blank human serum with benzodiazepine standards from 5 to 500 ng/mL. Semi-quantitative results were obtained using a single-point calibration (c = 50 ng/mL). Results The current spectral library contains 19 designer benzodiazepines, prescription benzodiazepines and metabolites. The method can easily be extended once new designer benzodiazepines emerge on the drug market or according to specific needs of the user. The LOD was 5 ng/mL except for six compounds only detected at concentrations above 10 ng/mL. Nifoxipam, known to have a poor ESI response and being highly instable in serum, was the only compound that could not be detected at practically relevant concentrations in serum. For each analyte, a linear calibration range (calLow to calHigh) was determined and calculated concentrations within this range are reported as semi-quantitative result in the automatically generated report. Findings below or above the linear range are reported as ‘ calHigh’, respectively. Semi-quantitative results were found to vary between ± 20 and ± 40% at the lower end of the calibration range and ± 10 to ± 25% at medium and high concentrations. Conclusion The presented method allows automated identification and semi-quantitative determination of 58 benzodiazepines, including 18 designer benzodiazepines. LOD in serum allow the detection below the desired or at the concentration needed for the majority of medical benzodiazepines, making the screening applicable for clinical research and forensic analysis. Semi-quantitative analysis enables a quick toxicological research evaluation of the results and helps to decide on the analytical strategy in case work. Although this approach requires a more time consuming sample preparation when compared to routine immunoassays, unambiguous identification and semi-quantitative determination of compounds also offers more detailed information.

Analysis of matrix-assisted laser desorption/ionization quadrupole time-of-flight collision-induced dissociation spectra of simple precursor ions and isobaric oligosaccharide ion mixtures based on product ion intensities and pattern recognition.

Qualitative analysis of glycomic tandem mass spectrometry (MS/MS) data based on m/z values of product ions alone is widely used, and often sufficient for analysis of single analytes. However, most complex glycomic mixtures contain multiple isobaric oligosaccharides, in which case this approach is often limited. Here we show how ion intensity information can be used in order to enhance MS/MS data analysis, and extract both qualitative and semiquantitative information from complex glycomic MS/MS datasets. A matrix-assisted laser desorption/ionization quadrupole time-of-flight (MALDI QTOF) mass spectrometer was used in this study. We compared the intensities of product ions within a single product ion series, determined by their length, across the whole glycomic MS/MS dataset. In order to detect discernable patterns, the intensity data was normalized to the intensity of each product ion within the series. In most cases, normalized data yielded easily discernable patterns, relevant either for analysis of specific glycomic structure types, or mechanistic MS studies. We used our approach on a glycomic sample consisting of human milk oligosaccharides. The approach yielded useful results for both qualitative and semiquantitative analyses. All normalizations performed were not equally rich in information and the information content of generated tables was not possible to predict. These analyses were shown to be independent of instrument manufacturer. Our approach enabled more detailed qualitative analysis of MS/MS spectra of precursor ions containing isobaric oligosaccharide structures. While limited semiquantitative information could be extracted from the raw data as well, the accuracy of this method should be significantly enhanced when standard calibration mixtures can be prepared. Copyright © 2017 John Wiley & Sons, Ltd.

A fast in situ non-invasive approach to classify mortars from a construction of high historical value

The use of hand-held X-ray fluorescence (HH-XRF) spectrometers has increased in the last years due to its easily portable capacity and its rapid and non-destructive analysis. In this work, HH-XRF is proposed as a fast in situ non-invasive technique to classify mortars from a construction of high historical value. The current HH-XRF devices are able to provide large amounts of information almost instantaneously based on Fundamental Parameters quantification methodology that especially for the analyses of samples with very complex matrixes such as building materials is not very reliable. The accuracy of the semi-quantitative information provided by the HH-XRF spectrometer was compared with a previously optimized WD-XRF quantification method and a complete spectral data treatment followed by Principal Component Analysis is also proposed to classify easily and quickly the mortars used in this construction, without a previous sampling procedure, according to the similarities/differences in their elemental composition.

SC01.02 PET-CT for Response Assessment During Induction Therapy of N2 NSCLC

Approximately 30% of patients with non-small cell lung cancer (NSCLC) are found to have locally advanced stage III tumors at initial diagnosis. For these patients the curative therapeutic options include definitive high-dose radiotherapy with concurrent chemotherapy or, alternatively, induction treatment followed by surgery. Preoperative chemotherapy or combined radiochemotherapy protocols followed by resection result in cure rates of 25-35 percent at 3 years for locally advanced NSCLC. However, surgical resection in patients with stage IIIa N2 remains an issue of controversy depending on the extent of lymph node involvement. Neoadjuvant chemo- or radiochemotherapy is being used to reduce disease burden in the mediastinum before surgery since patients who are downstaged via neoadjuvant therapy and then undergo resection experience a significantly longer 5-year survival of 40% to 50% than those who are found to have residual N2 disease at the time of surgery. Thus, identification of patients who are N2 negative after completion of their neoadjuvant therapy is a critical component for patient selection for thoracotomy. However, clinical restaging in these patients often is challenging. Endoscopic ultrasound guided biopsies (EUS/EBUS-FNA) have increasingly become available and are currently preferred procedures for staging and restaging before surgery due to their high diagnostic accuracy.1 Serial PET-CT imaging captures anatomical changes and additionally offers semiquantitative information about morphometric and metabolic tissue changes during induction treatment. Issues of PET-CT performance and quality assurance concerning standardization have been clarified during recent years and the validity of repeated measurements has been approved.2 Successful induction treatment regimens have been frequently found to reduce 18F-FDG uptake and thus PET-CT allows to assess the therapeutic response. Reduction in FDG-uptake of mediastinal lymph nodes after induction therapy has been shown to correlate well with histopathologic response,3 while postinduction PET avidity taken alone was not consistently found to be associated with pathological N2 involvement.4 In the direct comparison of EUS-FNA with PET-CT for restaging after induction chemoradiotherapy, concordance between findings of restaging EUS-FNA and metabolic response of lymph node metastases was observed in 63% patients treated within a prospective study but the diagnostic accuracy of PET-CT was limited.5 Nevertheless, serial FDG-uptake measurements seem to provide prognostic information during induction therapy. Data collected in prospective trials suggest that a decrease in SUVmax between 45% to 60% optimally separates between responders and non-responders.6-9 In a recent large retrospective analysis, a decrease in SUVmax greater than 60% in the involved mediastinal nodes was the best predictor of overall survival, better than changes seen in the primary tumor site.10 An analysis of a randomized trial in potentially resectable stage III NSCLC of induction treatment (including a hyperfractionated accelerated radiotherapy phase) and definitive radiochemotherapy compared with induction treatment followed by surgery confirmed that as early as after two cycles of cisplatin-based induction chemotherapy percentage of SUVmax remaining represents a significant prognostic parameter.9 PET-response was of higher importance than all other clinical factors. Cut-off levels between 0.45 and 0.55 were predictive for freedom from extracerebral progression in all randomized patients. No important differences in the predictive value were observed comparing resection versus definitive radiochemotherapy. PET-response was closely related to extracerebral distant metastases but not to local recurrences, independent of treatment. One might conclude that less PET-responsive tumors are successfully controlled by intensified hyperfractionated accelerated radiochemotherapy or neoadjuvant radiochemotherapy and resection at loco-regional sites so that the highest risk of relapse remains at extracerebral distant sites. Therefore, a selection or intensification of the local therapy according to SUV-decrease is not warranted by these data. Functional imaging has not yet been fully established for treatment guidance but prospective evaluation is underway. In the group of poor-responding patients, treatment intensification by independent systemic options such as targeted therapy or immunomodulating therapy may become emerging new treatment options within clinical trials. 1. De Leyn EJCTS 2014, 2. Young, EJC 1999, 3. Pöttgen CCR 2006, 4. Ripley JTCS 2016, 5. Stigt, Lung Cancer 2009, 6. Hoekstra, JCO 2005, 7. Eschmann, Lung Cancer 2007, 8. Dooms, JCO 2008, 9. Pöttgen, JCO 2016, 10. Barnett ATS 2016. PET-CT; N2; induction, restaging

Method development towards qualitative and semi-quantitative analysis of multiple pesticides from food surfaces and extracts by desorption electrospray ionization mass spectrometry as a preselective tool for food control.

Direct analysis of fruit and vegetable surfaces is an important tool for in situ detection of food contaminants such as pesticides. We tested three different ways to prepare samples for the qualitative desorption electrospray ionization mass spectrometry (DESI-MS) analysis of 32 pesticides found on nine authentic fruits collected from food control. Best recovery rates for topically applied pesticides (88%) were found by analyzing the surface of a glass slide which had been rubbed against the surface of the food. Pesticide concentration in all samples was at or below the maximum residue level allowed. In addition to the high sensitivity of the method for qualitative analysis, quantitative or, at least, semi-quantitative information is needed in food control. We developed a DESI-MS method for the simultaneous determination of linear calibration curves of multiple pesticides of the same chemical class using normalization to one internal standard (ISTD). The method was first optimized for food extracts and subsequently evaluated for the quantification of pesticides in three authentic food extracts. Next, pesticides and the ISTD were applied directly onto food surfaces, and the corresponding calibration curves were obtained. The determination of linear calibration curves was still feasible, as demonstrated for three different food surfaces. This proof-of-principle method was used to simultaneously quantify two pesticides on an authentic sample, showing that the method developed could serve as a fast and simple preselective tool for disclosure of pesticide regulation violations. Graphical Abstract Multiple pesticide residues were detected and quantified in-situ from an authentic set of food items and extracts in a proof of principle study.

Future research needs involving pathogens in groundwater

Contamination of groundwater by enteric pathogens has commonly been associated with disease outbreaks. Proper management and treatment of pathogen sources are important prerequisites for preventing groundwater contamination. However, non-point sources of pathogen contamination are frequently difficult to identify, and existing approaches for pathogen detection are costly and only provide semi-quantitative information. Microbial indicators that are readily quantified often do not correlate with the presence of pathogens. Pathogens of emerging concern and increasing detections of antibiotic resistance among bacterial pathogens in groundwater are topics of growing concern. Adequate removal of pathogens during soil passage is therefore critical for safe groundwater extraction. Processes that enhance pathogen transport (e.g., high velocity zones and preferential flow) and diminish pathogen removal (e.g., reversible retention and enhanced survival) are of special concern because they increase the risk of groundwater contamination, but are still incompletely understood. Improved theory and modeling tools are needed to analyze experimental data, test hypotheses, understand coupled processes and controlling mechanisms, predict spatial and/or temporal variability in model parameters and uncertainty in pathogen concentrations, assess risk, and develop mitigation and best management approaches to protect groundwater.

Micro-bubbles seeding for flow characterization

Micro-bubbles injection has long been used in hydrodynamic facilities for the control of dissolved and free air. In some cavitation tunnels [9], very large quantities of microbubbles (billions per second) are injected for rapid degassing and, in smaller quantities (millions per second), for cavitation nuclei seeding. Micro-bubbles can also be used as tracers for optical measurements including visualization, LDV or PIV. For these applications, bubbles must be sufficiently small to faithfully follow the flow. Depending on the quality and spatial characteristics of the micro-bubbles seeding, several optical methods can be applied: simple visualization gives access to semi-quantitative information on the behaviour of flows; LASER velocimetry provides information on the mean velocity and other temporal local characteristics of the flow. This paper presents some new micro-bubbles seeding devices recently developed by YLEC Consultants. These devices have been designed to fulfill specific requirements related to integration into cavitation tunnels and permit optical velocimetry measurement techniques such as Particle Image Velocimetry (PIV).The LEGI cavitation tunnel is the first tunnel which has been equipped with these microbubbles seeding systems dedicated to optical velocimetry. This paper presents the final integration schemes selected for micro-bubbles seeding into LEGI tunnel and discuss about practical concerns related to the use of the injection system for optical velocimetry.

Expression of CCN Genes and Proteins in Human Skin: Methods and Protocols.

CCN proteins are vital to a variety of biological processes that contribute to the normal development and function of skin. Quantitative real-time reverse transcriptase PCR (qPCR) quantifies mRNA levels of these key genes. Immunostaining localizes CCN proteins within skin tissue, and provides semiquantitative information regarding relative levels of the proteins. Reliable determinations of the expression levels of CCN genes and proteins are essential to uncovering their roles in skin physiology and pathology.

Development of a liquid chromatography high resolution mass spectrometry method for the quantitation of viral envelope glycoprotein in Ebola virus-like particle vaccine preparations.

Background Ebola virus like particles (EBOV VLPs, eVLPs), are produced by expressing the viral transmembrane glycoprotein (GP) and structural matrix protein VP40 in mammalian cells. When expressed, these proteins self-assemble and bud from ‘host’ cells displaying morphology similar to infectious virions. Several studies have shown that rodents and non-human primates vaccinated with eVLPs are protected from lethal EBOV challenge. The mucin-like domain of envelope glycoprotein GP1 serves as the major target for a productive humoral immune response. Therefore GP1 concentration is a critical quality attribute of EBOV vaccines and accurate measurement of the amount of GP1 present in eVLP lots is crucial to understanding variability in vaccine efficacy.MethodsAfter production, eVLPs are characterized by determining total protein concentration and by western blotting, which only provides semi-quantitative information for GP1. Therefore, a liquid chromatography high resolution mass spectrometry (LC-HRMS) approach for accurately measuring GP1 concentration in eVLPs was developed. The method employs an isotope dilution strategy using four target peptides from two regions of the GP1 protein. Purified recombinant GP1 was generated to serve as an assay standard. GP1 quantitation in 5 eVLP lots was performed on an LTQ-Orbitrap Elite and the final quantitation was derived by comparing the relative response of 200 fmol AQUA peptide standards to the analyte response at 4 ppm.ResultsConditions were optimized to ensure complete tryptic digestion of eVLP, however, persistent missed cleavages were observed in target peptides. Additionally, N-terminal truncated forms of the GP1 protein were observed in all eVLP lots, making peptide selection crucial. The LC-HRMS strategy resulted in quantitation of GP1 with a lower limit of quantitation of 1 fmol and an average percent coefficient of variation (CV) of 7.6 %. Unlike western blot values, the LC-HRMS quantitation of GP1 in 5 eVLP vaccine lots exhibited a strong linear relationship (positive correlation) with survival (after EBOV challenge) in mice.ConclusionsThis method provides a means to rapidly determine eVLP batch quality based upon quantitation of antigenic GP1. By monitoring variability in GP1 content, the eVLP production process can be optimized, and the total amount of GP1 needed to confer protection accurately determined.Electronic supplementary materialThe online version of this article (doi:10.1186/s12014-016-9119-8) contains supplementary material, which is available to authorized users.

13C-NMR studies on disulfide bond isomerization in bovine pancreatic trypsin inhibitor (BPTI)

Conformational isomerization of disulfide bonds is associated with the dynamics and thus the functional aspects of proteins. However, our understanding of the isomerization is limited by experimental difficulties in probing it. We explored the disulfide conformational isomerization of the Cys14-Cys38 disulfide bond in bovine pancreatic trypsin inhibitor (BPTI), by performing an NMR line-shape analysis of its Cys carbon peaks. In this approach, 1D (13)C spectra were recorded at small temperature intervals for BPTI samples selectively labeled with site-specifically (13)C-enriched Cys, and the recorded peaks were displayed in the order of the temperature after the spectral scales were normalized to a carbon peak. Over the profile of the line-shape, exchange broadening that altered with temperature was manifested for the carbon peaks of Cys14 and Cys38. The Cys14-Cys38 disulfide bond reportedly exists in equilibrium between a high-populated (M) and two low-populated states (m c14 and m c38). Consistent with the three-site exchange model, biphasic exchange broadening arising from the two processes was observed for the peak of the Cys14 α-carbon. As the exchange broadening is maximized when the exchange rate equals the chemical shift difference in Hz between equilibrating sites, semi-quantitative information that was useful for establishing conditions for (13)C relaxation dispersion experiments was obtained through the carbon line-shape profile. With respect to the m c38 isomerization, the (1)H-(13)C signals at the β-position of the minor state were resolved from the major peaks and detected by exchange experiments at a low temperature.

New Trends in the Design of Enzyme-based Biosensors for Medical Applications.

A biosensor is a self-contained integrated device, which is capable of providing specific quantitative or semiquantitative analytical information using a biological (or biomimetic) recognition element, which is retained in direct spatial contact with an electrochemical transduction element. One of the main features of biosensors is the remarkable selectivity that their biological components confer on them. Enzymes are the most common and well-developed recognition system of the family known as catalytic biosensors. This mini-review is focused on enzyme-based biosensors for medical applications. In particular, the new trends for the technology are described. A special emphasis is devoted to the non-invasive and painless monitoring of body metabolites, such as glucose.

Profiling the substitution pattern of xyloglucan derivatives by integrated enzymatic hydrolysis, hydrophilic-interaction liquid chromatography and mass spectrometry

Plant polysaccharides constitute arguably the most complex family of biomacromolecules in terms of the stereochemistry and regiochemistry of their intramolecular linkages. The chemical modification of such polysaccharides introduces an additional level of complexity for structural determinations. We have developed an integrated analytical procedure combining selective enzymatic hydrolysis, hydrophilic interaction liquid chromatography (HILIC), and mass spectrometry (MS) to describe the substitution pattern of xyloglucan (XyG) and its chemo-enzymatic derivatives (cationic, anionic, and benzyl aminated). Enzymatic hydrolysis of XyG derivatives by a xyloglucan-specific endoglucanase (XEG) generates oligosaccharides amenable for mass spectrometric identification with distinct structures, based on enzymatic substrate recognition and hydrolytic pattern. Matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI-ToF-MS) and electrospray ionisation mass spectrometry (ESI–MS) offer qualitative mass profiling of the chemical derivatives. Separation and identification of the complex oligosaccharide profiles released by enzymatic hydrolysis is achieved by hyphenation of hydrophilic interaction liquid chromatography with mass spectrometry (HILIC-ESI–MS). Further fragmentation by tandem mass spectrometry (ESI–MS/MS) in positive mode enables the structural sequencing of modified XyG oligosaccharides and the identification of the substituent position without further derivatisation. This integrated approach can be used to obtain semi-quantitative information of the substitution pattern of hemicellulose derivatives, with fundamental implications for their modification mechanisms and performance.

A diaper-embedded disposable nitrite sensor with integrated on-board urine-activated battery for UTI screening.

This paper reports a low-cost solution to the early detection of urinary nitrite, a common surrogate for urinary tract infection (UTI). We present a facile method to fabricate a disposable and flexible colorimetric [1] nitrite sensor and its urine-activated power source [2] on a hydrophobic (wax) paper through laser-assisted patterning and lamination. Such device, integrated with interface circuitry and a Bluetooth low energy (BLE) module can be embedded onto a diaper, and transmit semi-quantitative UTI monitoring information in a point-of-care and autonomous fashion. The proposed nitrite sensing platform achieves a sensitivity of 1.35 ms/(mg/L) and a detection limit of 4 mg/L.

Introduction to metabolomics and its applications in ophthalmology.

Metabolomics is the study of endogenous and exogenous metabolites in biological systems, which aims to provide comparative semi-quantitative information about all metabolites in the system. Metabolomics is an emerging and potentially powerful tool in ophthalmology research. It is therefore important for health professionals and researchers involved in the speciality to understand the basic principles of metabolomics experiments. This article provides an overview of the experimental workflow and examples of its use in ophthalmology research from the study of disease metabolism and pathogenesis to identification of biomarkers.

Immunolocalization of immune cells and cell cycle proteins in the bulbus arteriosus of Atlantic salmon (Salmo salar L.).

The bulbus arteriosus is the most anterior chamber of the teleost heart. The present study aimed to establish the presence, and to provide semi-quantitative information on the abundance, of several immune and cell-cycle proteins in the bulbus arteriosus of healthy Atlantic salmon (Salmo salar L.). Using immunohistochemistry, lymphocyte-like cells were identified in the bulbus arteriosus using antibodies to CD3ε and MHC class IIβ. Few PCNA positive cells were identified in post-smolt fish as compared to moderate levels of staining in fresh water fry. Interestingly no staining was evident in adult fish (1-3kg), thus there was a loss of cells expressing cell-cycle regulatory proteins with ontogeny/progressive life-history stages. Eosinophilic granulocytes (EGCs) were identified in the bulbus arteriosus using TNFα and HIF1α antibodies. Anti-caspase 3 immune-reaction identified a strong endothelial cytoplasmic staining in the bulbus arteriosus. Taken together, the immunolocalization of immune-related molecules (CD3, MHC class II and TNFα), cell-cycle regulatory proteins (PCNA and HIF1α) and apoptosis markers (TUNEL, caspase 3) suggest that the bulbus arteriosus may have an immune component within its functional repertoire.

Environmental Hf–Nd isotopic decoupling in World river clays

The hafnium and neodymium radiogenic isotope systems behave differently during Earth surface processes, causing a wide dispersion of Hf and Nd isotopic compositions in sediments and other sedimentary rocks. The decoupling between Hf and Nd isotopes in sediments is generally attributed to a combination of preferential sorting of zircon during sediment transport and incongruent weathering processes on continents. In this study, we analysed size-fractions of sediment samples collected near the mouth of 53 rivers worldwide to better understand the factors controlling the distribution of Hf and Nd isotopes in sediments. Our results for rivers draining old cratonic areas and volcanic provinces demonstrate that both granite and basalt weathering can lead to significant grain-size dependent Hf isotopic variability. While silt-size fractions mainly plot along the Terrestrial Array, World river clays are systematically shifted towards more radiogenic Hf isotopic compositions, defining together with published data a new Clay Array (εHf=0.78×εNd+5.23). The Hf–Nd isotope decoupling observed in volcanogenic sediments is best explained by selective alteration of Lu-rich mineral phases (e.g. olivine) and preferential enrichment of resistant unradiogenic minerals, such as spinel and ilmenite, in silt fractions. We also show that the extent to which World river clays deviate from the Clay Array (ΔεHf clay) is not linked to the presence of zircons. Instead, it correlates positively with weathering indices and climatic parameters (temperature, rainfall) of the corresponding drainage basins. Overall, these findings demonstrate that the distribution of Hf–Nd isotopes in clay-size sediments is related to a large extent to weathering conditions on continents, although the precise mechanisms controlling this relationship remain unclear. We finally propose that the Hf–Nd isotope pair proxy could be used in palaeoenvironmental studies to provide semi-quantitative information on past climates.

Magnetic Resonance Imaging: Advanced Applications in Breast Cancer

Breast MRI is a highly sensitive imaging tool for breast cancer detection. In general clinical practice, breast MRI utilizes a limited dynamic contrast-enhanced (DCE) acquisition that provides morphologic and semi-quantitative kinetic information to allow characterization of breast findings. This approach provides sensitivities approaching 100 % for breast cancer detection; however, its specificity remains moderate due to limited ability to differentiate benign pathologic processes that enhance from malignancies. Several advanced MRI techniques, such as high-temporal resolution DCE that allows robust quantitative pharmacokinetic analysis, diffusion-weighted imaging that allows microstructural characterization, and MR spectroscopy that reflects chemical composition, hold promise to improve standard breast MRI specificity and to serve as imaging biomarkers that can guide treatment decisions. In this review article, we review recent updates in advanced breast MRI applications, including their potential clinical uses and challenges to implementation.

(18)F-FDG PET/CT quantification in head and neck squamous cell cancer: principles, technical issues and clinical applications.

(18)F-FDG PET/CT plays a crucial role in the diagnosis and management of patients with head and neck squamous cell cancer (HNSCC). The major clinical applications of this method include diagnosing an unknown primary tumour, identifying regional lymph node involvement and distant metastases, and providing prognostic information. (18)F-FDG PET/CT is also used for precise delineation of the tumour volume for radiation therapy planning and dose painting, and for treatment response monitoring, by detecting residual or recurrent disease. Most of these applications would benefit from a quantitative approach to the disease, but the quantitative capability of (18)F-FDG PET/CT is still underused in HNSCC. Innovations in PET/CT technology promise to overcome the issues that until now have hindered the employment of dynamic procedures in clinical practice and have limited "quantification" to the evaluation of standardized uptake values (SUV), de facto a semiquantitative parameter, the limits of which are well known to the nuclear medicine community. In this paper the principles of quantitative imaging and the related technical issues are reviewed so that professionals involved in HNSCC management can reflect on the advantages of "true" quantification. A discussion is then presented on how semiquantitative information is currently used in clinical (18)F-FDG PET/CT applications in HNSCC, by discussing the improvements that could be obtained with more advanced and "personalized" quantification techniques.

Reliability Assessment of Cloud Computing Platform Based on Semiquantitative Information and Evidential Reasoning

A reliability assessment method based on evidential reasoning (ER) rule and semiquantitative information is proposed in this paper, where a new reliability assessment architecture including four aspects with both quantitative data and qualitative knowledge is established. The assessment architecture is more objective in describing complex dynamic cloud computing environment than that in traditional method. In addition, the ER rule which has good performance for multiple attribute decision making problem is employed to integrate different types of the attributes in assessment architecture, which can obtain more accurate assessment results. The assessment results of the case study in an actual cloud computing platform verify the effectiveness and the advantage of the proposed method.

99mTc-conjugated manganese-based mesoporous silica nanoparticles for SPECT, pH-responsive MRI and anti-cancer drug delivery.

In recent decades, hybrid imaging techniques that exploit the advantages of multiple imaging technologies have aroused extensive attention due to the deficiencies of single imaging modes. Along with the development of single photon emission computed tomography-magnetic resonance imaging (SPECT-MRI), it is currently necessary to develop a series of dual probes that can combine the outstanding sensitivity of SPECT with the high spatial resolution of MRI. Herein, the commonly used technetium-99 (99mTc) was labelled on the surface of manganese oxide-based mesoporous silica nanoparticles (MnOx-MSNs) for use in SPECT-MRI dual-modal imaging. The radiolabelling yield was as high as 99.1 ± 0.6%, and the r1 value of the nanoprobes was able to reach 6.60 mM-1 s-1 due to the pH-responsive properties of the MnOx-MSNs. The high-performance SPECT-MRI dual-modal imaging was confirmed in vivo in tumour-bearing mice, which could also provide semi-quantitative information for tumour detection. Importantly, these nanoprobes can deliver anti-cancer drugs in cancer therapy due to their unique mesoporous structures. Thus, nanotheranostics combining dual-modal imaging with anti-cancer therapeutic properties were achieved.