Signal Intensity Enhancement Research Articles

Correlation of dynamic contrast-enhanced MRI and diffusion-weighted MR imaging with prognostic factors and subtypes of breast cancers.

ObjectiveTo determine the preoperative magnetic resonance imaging (MRI) findings of breast cancer on dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and diffusion-weighted magnetic resonance imaging (DWI) in different molecular subtypes.Materials and methodsA retrospective study was conducted on 116 breast cancer subjects who underwent preoperative MRI and surgery or biopsy. Three radiologists retrospectively assessed the morphological and kinetic characteristics on DCE-MRI and tumor detectability on DWI, by using apparent diffusion coefficient (ADC) values of lesions. The clinicopathologic and MRI features of four subtypes were compared. The correlation between clinical and MRI findings with molecular subtypes was evaluated using the chi-square and ANOVA tests, while the Mann–Whitney test was used to analyze the relationship between ADC and prognostic factors.ResultsOne hundred and sixteen women diagnosed with breast cancer confirmed by surgery or biopsy had the following subtypes of breast cancer: luminal A (27, 23.3%), luminal B (56, 48.2%), HER2 positive (14, 12.1%), and triple-negative breast cancer (TNBC) (19, 16.4%), respectively. Among the subtypes, significant differences were found in axillary node metastasis, histological grade, tumor shape, rim enhancement, margin, lesion type, intratumoral T2 signal intensity, Ki-67 index, and paratumoral enhancement (p < 0.001, p < 0.001, p < 0.001, p < 0.001, p < 0.001, p < 0.001, p < 0.001, p < 0.001, and p = 0.02, respectively). On DWI, the mean ADC value of TNBC (0.910 × 10−3 mm2/s) was the lowest compared to luminal A (1.477×10−3 mm2/s), luminal B (0.955 × 10−3 mm2/s), and HER2 positive (0.996 × 10−3 mm2/s) (p < 0.001). Analysis of the correlation between different prognostic factors and ADC value showed that only axillary lymph node status and ADC value had a statistically significant difference (p = 0.009).ConclusionThe morphologic features of MRI can be used as imaging biomarkers to identify the molecular subtypes of breast cancer. In addition, quantitative assessments of ADC values on DWI may also provide biological clues about molecular subtypes.

A comprehensive study about the in-cloud processing of nitrate through coupled measurements of individual cloud residuals and cloud water

Abstract. While the formation and evolution of nitrate in airborne particles are extensively investigated, little is known about the processing of nitrate in clouds. Here we present a detailed investigation on the in-cloud formation of nitrate, based on the size-resolved mixing state of nitrate in the individual cloud residual and cloud-free particles obtained by single particle mass spectrometry, and also the mass concentrations of nitrate in the cloud water and PM2.5 at a mountain site (1690 m a.s.l. – above sea level) in southern China. The results show a significant enhancement of nitrate mass fraction and relative intensity of nitrate in the cloud water and the cloud residual particles, respectively, reflecting a critical role of in-cloud processing in the formation of nitrate. We first exclude the gas-phase scavenging of HNO3 and the facilitated activation of nitrate-containing particles as the major contribution for the enhanced nitrate, according to the size distribution of nitrate in individual particles. Based on regression analysis and theoretical calculations, we then highlight the role of N2O5 hydrolysis in the in-cloud formation of nitrate, even during the daytime, attributed to the diminished light in clouds. Nitrate is highly related (R2= ∼ 0.6) to the variations in [NOx][O3], temperature, and droplet surface area in clouds. Accounting for droplet surface area greatly enhances the predictability of the observed nitrate, compared with using [NOx][O3] and temperature. The substantial contribution of N2O5 hydrolysis to nitrate in clouds with diminished light during the daytime can be reproduced by a multiphase chemical box model. Assuming a photolysis rate at 30 % of the default setting, the overall contribution of N2O5 hydrolysis pathway to nitrate formation increases by ∼ 20 % in clouds. Given that N2O5 hydrolysis acts as a major sink of NOx in the atmosphere, further model updates would improve our understanding about the processes contributing to nitrate production in cloud and the cycling of odd nitrogen.

High-Grade Supratentorial Intraventricular Tumours in Adults.

High-grade Intraventricular tumours are rarely encountered. Many of these tumours will have similar patterns on imaging of signal intensity and contrast enhancement. As IVT are regularly not targetable by radiation or systemic therapy, until now, surgical resection presents the treatment of choice.

Electromembrane Extraction and Dual-Channel Nanoelectrospray Ionization Coupled with a Miniature Mass Spectrometer: Incorporation of a Dicationic Ionic Liquid-Induced Charge Inversion Strategy.

Green analytical chemistry aims at developing analytical methods with minimum use and generation of hazardous substances for the protection of human health and the environment. To address this need, a green analytical protocol has been developed for the analysis of anionic compounds integrating electromembrane extraction (EME), dual-channel nanoelectrospray ionization (nanoESI), and a miniature mass spectrometer. Haloacetic acids (HAAs) have attracted considerable public concern due to their adverse effects on human health and were selected as model analytes for method development. A flat membrane EME device was developed and assembled in-house. Optimization of fundamental operational parameters was performed using single-factor test and response surface methodology. Both the EME acceptor phase and an imidazolium-based dicationic ionic liquid (DIL), 1,1-bis(3-methylimidazolium-1-yl) butylene difluoride (C4(MIM)2F2), were subjected to dual-channel nanoESI and miniature mass spectrometry analysis based on a charge inversion strategy, where positively charged complexes were formed. Enhancement in signal intensity by as much as 2 magnitudes was achieved in the positive-ion mode compared to the negative-ion mode in the absence of the dicationic ion-pairing agent. The developed protocol was validated, obtaining good recoveries ranging from 82.7 to 109.9% and satisfactory sensitivity with limits of detection (LODs) and quantitation (LOQs) in the ranges of 1-5 and 2-10 μg/L, respectively. The greenness of the analytical procedure was assessed with a calculated score of 0.71, indicating a high degree of greenness. The developed method was applied to the analysis of real environmental or municipal water samples (n = 16), exhibiting appealing potential for outside-the-laboratory applications.

PB2306: RELAPSE OF IMMUNE THROMBOCYTOPENIA AND MYOCARDITIS

Background: Immune thrombocytopenia (ITP) is an acquired thrombocytopenia caused by autoantibodies against platelet antigens. ITP most often occurs within a few weeks following a viral infection, but it is also associated with other infections, drugs, hematopoietic malignancies and autoimmune diseases. Myocarditis is an inflammatory disease of cardiac muscle caused by a variety of infectious and noninfectious conditions. Autoimmune mechanisms have been implicated in the pathogenesis of myocarditis with or without a virus trigger. Aims: Our aim is to present an unusual case of myocarditis in a 17-year-old male, with a history of ITP presenting simultaneous relapse of ITP. Methods: A 17-year-old male with a history of ITP presented at the Emergency Department complaining of gingival bleeding, left shoulder pain and fever. Clinical examination showed extremity petechiaes and tachycardia, there was an ST elevation in V2-V6 leads on ECG and laboratory data included PLTs 2000/μL and elevated high sensitivity troponin (1.240pg/mL). He was treated immediately as a relapse of ITP with corticosteroids and he received b-blockers due to persistent tachycardia. Viral and immunological tests were negative. Results: Gradually, during hospitalization, there was an elevation of PLT count and a decrease in serum troponin levels with improving and finally normal ECG findings. The patient was discharged and continued treatment with prednisolone and b-blocker. He was reassessed after one month and troponin levels, PLT counts and ECG were normal. However, the cardiac Magnetic Resonance Imaging (MRI) revealed fibrosis with signal intensity and gadolium enhancement in the anterolateral and inferior segments. After three months a follow up cardiac MRI showed reduction of fibronitic tissue size. Summary/Conclusion: Autoimmunity plays a major role in the pathogenesis of both ITP and myocarditis. It seems that they share common autoimmune pathways and further research of which is important for understanding pathophysiology behind these clinical entities and improving their treatment.

Quantitative determination of LY-404,039, a metabotropic glutamate 2/3 receptor agonist, in rat plasma using chemical derivatization and HPLC-MRM/MS.

A rapid, selective and sensitive method was developed and validated for the determination of LY-404,039 concentration in rat plasma using a butylation derivatization step to improve chromatographic characteristics and enhance signal intensity. The method consisted of a protein precipitation extraction followed by derivatization with butanol/HCl and analysis by high-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS). The separation was achieved using a 100 × 2.1mm (2.6μm) Thermo Scientific Accucore RP-MS column combined with an isocratic mobile phase composed of 40:60 acetonitrile-0.1% formic acid in water. An analytical range of 2.0-1,000 ng/ml was validated and used to quantify LY-404,039 in rat plasma. The novel method met all of the requirements of specificity, sensitivity, linearity, precision, accuracy and stability. A pharmacokinetic study was performed in rats and the novel analytical method was used as a routine analysis method to provide enhanced measurements of plasma concentrations of LY-404,039. The plasma pharmacokinetic results indicate very short terminal half-life (0.27 h ± 0.8) and high clearance (0.97 L/h/kg ± 0.12), suggesting that LY-404,039 is rapidly eliminated in the rat. Dose-dependent pharmacokinetics were observed following subcutaneous administration of LY-404,039 at doses of 0.1, 0.3 and 1.0mg/kg.

Dual-Resistance of Ion Migration and Moisture Erosion via Hydrolytic Crosslinking of Siloxane Functionalized Poly(Ionic Liquids) for Efficient and Stable Perovskite Solar Cells

Dual-Resistance of Ion Migration and Moisture Erosion via Hydrolytic Crosslinking of Siloxane Functionalized Poly(Ionic Liquids) for Efficient and Stable Perovskite Solar Cells

Comparative study of radiologists vs machine learning in differentiating biopsy-proven pseudoprogression and true progression in diffuse gliomas

Background and PurposeMRI features of tumor progression and pseudoprogression may be indistinguishable especially without enhancing portion of the diffuse gliomas. Our aim is to discriminate these two conditions using radiomics and machine learning algorithm and to compare them with human observations. Materials and MethodsThree consecutive MRI studies before a definitive biopsy in 43 diffuse glioma patients (7 pseudoprogression and 36 true progression cases) who underwent treatment were evaluated. Two neuroradiologists reviewed pre- and post-contrast T1, T2, FLAIR, ADC, rCBV, rCBF, K2, and MTT maps. Patterns of enhancement, ADC maps, rCBV, rCBF, MTT, K2 values, and perilesional FLAIR signal intensity changes were recorded. Odds ratios (OR) for each descriptor, raters' success in predicting true and pseudoprogression, and inter-observer reliability were calculated using the R statistics software. Unpaired Student's t-test and receiver operating characteristic (ROC) analysis were applied to compare the texture parameters and histogram analysis of pseudo- and true progression groups. All first-order and second-order image texture features and shape features were used to train and test the Random Forest classifier (RFC). Observers' success and RFC were compared. ResultsObservers could not identify true progression in the first visit. However, accuracy of the RFC model was 81%. For the second and third visits, the rater's success of prediction was between 62% and 72%. The accuracy for the second and last visit with RFC was 75% and 81%. ConclusionsRandom Forest classifier was more successful than human observations in predicting pseudoprogression using MRI.

Acquired cystic disease subtype renal cell carcinoma (ACD-RCC): prevalence and imaging features at a single institution.

Acquired cystic kidney disease (ACKD) is commonly seen in patients with end-stage renal disease (ESRD), and patients with ACKD have an increased risk of renal cell carcinoma (RCC). Acquired cystic disease-associated RCC (ACD-RCC) was incorporated into the 2016 World Health Organization Classification. This study aims to describe the imaging features of ACD-RCC, which are not well reported previously. Retrospective review of patients with ACKD who underwent total nephrectomy for concern of a renal mass between 2016 and 2021 yielded 122 nephrectomies in 107 patients. Pathology reports were searched for type and subtype of mass. In ACD-RCC subtypes, imaging studies were evaluated for modality and contrast enhancement (CE). Imaging findings assessed included cystic/solid nature, unenhanced CT (NECT) attenuation, enhancement characteristics [non-enhancing (< 10 HU difference), equivocal (10-20 HU), enhancing (> 20 HU)], subjective MRI enhancement, T1 and T2 signal intensity, restricted diffusion, ultrasound (US) echogenicity, and subjective CEUS enhancement. 148 masses were identified, 122 (82%) of which were malignant and 26 (18%) benign. The three most common tumors were clear cell RCC (n = 47), papillary RCC (n = 35), and ACD-RCC (n = 21). Of the 21 cases of ACD-RCC, 16 had preoperative imaging: CT (15: 6 NECT only, 2 CECT only, 7 combined NECT and CECT), MRI (4), CEUS (5). Ten of these tumors were solid/mostly solid and 6 mixed cystic/solid. On NECT, the average attenuation was 35 HU (range 13-52). Of those with multiphasic CTs, 1 was non-enhancing, 3 were equivocal, and 3 enhanced. All 3 masses imaged with CE-MRI showed enhancement. All 4 tumors evaluated by MRI demonstrated T2 hypointensity and restricted diffusion. All five masses enhanced on CEUS. ACD-RCC subtype was the third most common renal neoplasm in ACKD patients. Our findings found that no single imaging feature is pathognomonic for ACD-RCC. However, ACD-RCCs are typically solid masses with most demonstrating equivocal or mild enhancement on CT. T2 hypointensity and restricted diffusion were the most common MRI features.

NMR and vibrational spectroscopic studies on the structure and self-assembly of Two de novo dipeptides in methanol

Short peptides are known to form self-organized nano-architectures useful for advanced biomedical applications. Both hydrogen-bonding and hydrophobic interactions play a pivotal role in molecular assembly, including self-assembly of proteins and peptides. In the current investigation, we reported the synthesis, self-assembly pattern and physicochemical properties of two de novo dipeptides: N-Boc-(O-benzyl)-tyro-(dimethyl)-glutamate and N-Boc-(O-benzyl)-glu-(O-benzyl)-tyrosine-methyl ester, abbreviated as P1 and P2, respectively. These two peptides produced different morphological features under similar conditions due to the presence of a small twist in their molecular structures. In methanol, P1 gave rise to a unique fibrillar network whereas P2 self-assembled into oligomers of 20-30 nm diameters. The UV-Vis, FT-IR and Raman spectra were recorded using experimental methods and compared with the computational spectra obtained by density functional method (B3LYP/6-31G(d)). The electronic absorption spectra of both P1 and P2 measured in methanol showed broad absorption peaks in the UV region with an absorption maximum at ∼ 273 nm. FT-IR and Raman spectra of both the dipeptides in solid state showed amide I vibration bands at ∼1650 cm−1 indicating a similar conformation state of the peptide bonds. However, H/D exchange 1H NMR measurements confirmed that the amide NH of P1 was strongly involved in H-bond formation compared to P2 amide NH and rapid H/D exchange occurred upon addition of D2O in the solution. Thioflavin T (ThT) fluorescence assay measurement suggested that incubation of P1 in methanol at room temperature produced fibrillar aggregates enriched with compact ß-sheet conformation. Formation of such ordered structure also caused a blue shift in the amide-carbonyl Raman frequency of the peptide to ∼1657 cm−1. P1 fibrils further showed gel formation behaviour in 1:1 methanol/water mixture. The minimum gelation concentration (MGC) of the dipeptide was found to be 0.5% w/v and the calculated gelation temperature (Tgel) of the corresponding MGC was 67°C. On the other hand, the amide carbonyl stretching vibration of P2 appeared at ∼1650 cm−1 in the Raman spectra and it was not significantly altered in its oligomeric state (produced in methanol).Moreover, no significant enhancement of ThT fluorescence intensity of P2 indicating absence of compact ß-sheet conformation of the peptide. The P2 oligomers also showed no gel like phase transformation in methanol/water mixtures.

Investigation on the effect of vacuum annealing time on structural and optical properties of YAG:Ce nanoparticles prepared by mixed-fuel microwave solution combustion synthesis

Cerium doped yttrium aluminum garnet (YAG:Ce) nanoparticles were synthesized via mixed-fuel microwave solution combustion synthesis and further optimized by post annealing treatment. The effects of vacuum annealing time and ambient on the phosphor structural, morphological, compositional, and optical properties were investigated in detail. The structural study performed with X-ray diffraction analysis and Rietveld refinement revealed a direct crystallization from amorphous into single phase YAG:Ce was achieved at 1050 °C for 1 h. The increase in annealing time enhances the powder crystallinity and promotes crystal growth to form larger particles (50–85 nm). However, prolonged annealing would cause the partial oxidation of Ce3+ into optically inert Ce4+ ions, which was likely due to the increased Ce segregation. X-ray photoelectron spectroscopy evidenced that vacuum annealing has a higher tendency to suppress Ce3+ oxidation in comparison to air annealing, resulting in a significant enhancement of photoluminescence emission intensity by 20%. The optimum emission intensity was obtained for YAG:Ce nanoparticles after 5 h of vacuum annealing treatment with color coordinates of (0.391, 0.569). The white light emitting diode (WLED) fabricated with the optimized YAG:Ce nanoparticles showed a cool-white light with a maximum luminous efficacy of radiation of 285 lm/W and a corresponding color rendering index of 83.

New Trends in Nanoarchitectured SERS Substrates: Nanospaces, 2D Materials, and Organic Heterostructures

This article reviews recent fabrication methods for surface-enhanced Raman spectroscopy (SERS) substrates with a focus on advanced nanoarchitecture based on noble metals with special nanospaces (round tips, gaps, and porous spaces), nanolayered 2D materials, including hybridization with metallic nanostructures (NSs), and the contemporary repertoire of nanoarchitecturing with organic molecules. The use of SERS for multidisciplinary applications has been extensively investigated because the considerably enhanced signal intensity enables the detection of a very small number of molecules with molecular fingerprints. Nanoarchitecture strategies for the design of new NSs play a vital role in developing SERS substrates. In this review, recent achievements with respect to the special morphology of metallic NSs are discussed, and future directions are outlined for the development of available NSs with reproducible preparation and well-controlled nanoarchitecture. Nanolayered 2D materials are proposed for SERS applications as an alternative to the noble metals. The modern solutions to existing limitations for their applications are described together with the state-of-the-art in bio/environmental SERS sensing using 2D materials-based composites. To complement the existing toolbox of plasmonic inorganic NSs, hybridization with organic molecules is proposed to improve the stability of NSs and selectivity of SERS sensing by hybridizing with small or large organic molecules.

Observations of a Flare-ignited Broad Quasiperiodic Fast-propagating Wave Train

Large-scale extreme-ultraviolet (EUV) waves are frequently observed as an accompanying phenomenon of flares and coronal mass ejections (CMEs). Previous studies mainly focused on EUV waves with single wave fronts that are generally thought to be driven by the lateral expansion of CMEs. Using high spatiotemporal resolution multi-angle imaging observations taken by the Solar Dynamics Observatory and the Solar Terrestrial Relations Observatory, we present the observation of a broad quasiperiodic fast-propagating (QFP) wave train composed of multiple wave fronts along the solar surface during the rising phase of a GOES M3.5 flare on 2011 February 24. The wave train transmitted through a lunate coronal hole (CH) with a speed of ∼840 ± 67 km s−1, and the wave fronts showed an intriguing refraction effect when they passed through the boundaries of the CH. Due to the lunate shape of the CH, the transmitted wave fronts from the north and south arms of the CH started to approach each other and finally collided, leading to a significant intensity enhancement at the collision site. This enhancement might hint at the occurrence of interference between the two transmitted wave trains. The estimated magnetosonic Mach number of the wave train is about 1.13, which indicates that the observed wave train was a weak shock. Period analysis reveals that the period of the wave train was ∼90 s, in good agreement with that of the accompanying flare. Based on our analysis results, we conclude that the broad QFP wave train was a large-amplitude fast-mode magnetosonic wave or a weak shock driven by some nonlinear energy release processes in the accompanying flare.

Spatial confinement effects of laser-induced breakdown spectroscopy at reduced air pressures

Spatial confinement is a simple and cost-effective method for enhancing signal intensity and improving the detection sensitivity of laser-induced breakdown spectroscopy (LIBS). However, the spatial confinement effects of LIBS under different pressures remains a question to be studied, because the pressure of the ambient gas has a significant influence on the temporal and spatial evolution of plasma. In this study, spatial confinement effects of LIBS under a series of reduced air pressures were investigated experimentally, and the plasma characteristics under different air pressures were studied. The results show that the reduced air pressure can lead to both earlier onset and weakening of the enhancement effect of the spatial confinement on the LIBS line intensity. When the air pressure drops to 0.1 kPa, the enhancement effect of the emission intensity no longer comes from the compression of the reflected shock wave on the plasma, but from the cavity’s restriction of the plasma expansion space. In conclusion, the enhancement effect of spatial confinement technology on the LIBS is still effective when the pressure is reduced, which further expands the research and application field of spatial confinement technology.Graphical abstract

Amplification of an Amplitude Modulated Electromagnetic Pulse Through Nonlinear Self-Compression

An electromagnetic short laser pulse is considered as amplitude modulated in time. To study the advancement of amplitude-modulated short laser pulses in a plasma, we preformed numerical modelling using time-dependent generalized nonlinear Schrödinger wave equation. This analysis is limited to one-dimensional geometry, as the transverse profile is considered as uniform. Paraxial like approach is used to derive dimensionless nonlinear pulse-compression parameter equation. The effect of amplitude modulation on nonlinear compression is studied. A significant enhancement in laser intensity is observed due to the amplitude modulation of the electromagnetic pulse. We observe about 50% increase in laser intensity as compared to the unmodulated laser pulse. Our results may be useful in the clean and affordable energy goal of sustainable development goals.

Cellulose Acetate-Based Plasmonic Crystals for Surface-Enhanced Raman and Fluorescence Spectroscopy.

In order to meet environmental concerns, there is an increasing demand for biodegradable and sustainable materials in many areas, including photonics. Cellulose and its derivatives are potentially eco-friendly alternatives to conventional plastics, because of their abundance and lower environmental impact. Here, we report the fabrication of plasmonic structures by molding cellulose acetate into submicrometric periodic lattices, using soft lithography. The fabricated platforms can be used for the enhancement of Raman and fluorescence signals of a range of analytes including a model immunoassay utilizing a streptavidin-conjugated dye, which is characterized by a 23-fold enhancement in fluorescence signal intensity, which shows the potential of the platform to be further used for the assay-based development of diagnostic tools.

Metal-enhanced fluorescence of graphene oxide sheets.

Graphene oxide (GO) is an excellent chemical tunable optical platform for imaging and sensing. The photoluminescence (PL) quantum yield of GO is relatively low, which limited the application of the intrinsic and tunable fluorescence from GO. Here, we report the first case of metal-enhanced fluorescence (MEF) of GO. A significant enhancement (~10-fold) in fluorescence intensity is observed from GO on the Ag substrate as compared to that on the glass. FL, Raman, and SEM images are used to investigate the MEF behavior and are coincident with each other. The influence of the metal particle size of Ag substrate is investigated. The fluorescence is also found to be responsive when adding different metal ions into GO solution. GO contacting directly with metal substrate exhibits strong MEF without quenching, which makes it possible to use GO sheets for three-dimension optical imaging and sensing.

Seasonal to sub-seasonal variations of the Asian Tropopause Aerosols Layer affected by the deep convection, surface pollutants and precipitation

The Asian Tropopause Aerosols Layer (ATAL) refers to an accumulation of aerosols in the upper troposphere and lower stratosphere during boreal summer over Asia, which has a fundamental impact on the monsoon system and climate change. In this study, we primarily analyze the seasonal to sub-seasonal variations of the ATAL and the factors potentially influencing those variations based on MERRA2 reanalysis. The ability of the reanalysis to reproduce the ATAL is well validated by CALIPSO observations from May to October 2016. The results reveal that the ATAL has a synchronous spatiotemporal pattern with the development and movement of the Asian Summer Monsoon. Significant enhancement of ATAL intensity is found during the prevailing monsoon period of July–August, with two maxima centered over South Asia and the Arabian Peninsula. Owing to the fluctuations of deep convection, the ATAL shows an episodic variation on a timescale of 7–12 days. Attribution analysis indicates that deep convection dominates the variability of the ATAL with a contribution of 62.7%, followed by a contribution of 36.6% from surface pollutants. The impact of precipitation is limited. The ATAL further shows a clear diurnal variation: the peak of ATAL intensity occurs from 17:30 to 23:30 local time (LT), when the deep convection becomes strongest; the minimum ATAL intensity occurs around 8:30 LT owing to the weakened deep convection and photochemical reactions in clouds. The aerosol components of the ATAL show different spatiotemporal patterns and imply that black carbon and organic carbon come mainly from India, whereas sulfate comes mainly from China during the prevailing monsoon period.

Effects of dopants in the imaging of mouse brain by desorption electrospray ionization/post-photoionization mass spectrometry.

Desorption electrospray ionization/post-photoionization (DESI/PI) is a newly developed ionization method by the combination of DESI and post-photoionization for the simultaneous imaging of polar and nonpolar compounds in biological tissues. Dopants are of great importance in DESI/PI for the enhancement of signal intensities through ion-molecule reactions. In this work, to evaluate the performance of dopants in DESI/PI, an efficient homogenate model was developed, and four kinds of dopants (toluene, chlorobenzene, bromobenzene, and anisole) were tested using homogenate of mouse brain tissue as target sample. The influences of the dopants on the signal enhancements of different compounds were explained reasonably by the ionization mechanism. Then, the dopants with their optimum volume contents were applied to the mass spectrometry imaging (MSI). For a comprehensive imaging of various compounds with different polarities, methanol/toluene/formic acid (7:3:0.1) was chosen as the best choice. Finally, the stronger quantitative ability of DESI/PI with toluene as dopant for a few compounds in mouse brain tissue was demonstrated.

On-tissue amidation of sialic acid with aniline for sensitive imaging of sialylated N-glycans from FFPE tissue sections via MALDI mass spectrometry.

Spatial visualization of glycans within clinical tissue samples is critical for discovery of disease-relevant glycan dysregulations. Herein, we develop an on-tissue derivatization strategy for sensitive spatial visualization of N-glycans from formalin-fixed paraffin-embedded (FFPE) tissue sections, based on amidation of sialic acid residues with aniline. The sialylated N-glycans were stabilized and given enhanced signal intensity owing to selective capping of a phenyl group to the sialic acid residue after aniline labeling. Proof-of-concept experiments, including determinations of sialylglycopeptide and N-glycans enzymatically released from glycoproteins, were performed. Further, mass spectrometry (MS) imaging of N-glycans on human laryngeal cancer FFPE tissue sections was conducted via matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI), based on our strategy for on-tissue amidation of sialylated N-glycans. We obtained higher sialylated N-glycan coverages for both the glycoproteins and cancer tissue samples, demonstrating that the detection sensitivity for sialylated N-glycans is notably improved by amidation derivatization. We also characterized N-glycan heterogeneity across the human laryngeal cancer tissue section, showing N-glycan dysregulation in the tumor region.