MALDI imaging mass spectrometry for direct tissue analysis: a new frontier for molecular histology

Matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry (IMS) is a powerful tool for investigating the distribution of proteins and small molecules within biological systems through the in situ analysis of tissue sections. MALDI-IMS can determine the distribution of hundreds of unknown compounds in a single measurement and enables the acquisition of cellular expression profiles while maintaining the cellular and molecular integrity. In recent years, a great many advances in the practice of imaging mass spectrometry have taken place, making the technique more sensitive, robust, and ultimately useful. In this review, we focus on the current state of the art of MALDI-IMS, describe basic technological developments for MALDI-IMS of animal and human tissues, and discuss some recent applications in basic research and in clinical settings

ϕ\phi Meson Production in In-In Collisions and the ϕ\phi Puzzle

The NA60 experiment measured dimuon production in In-In collisions at 158 AGeV. This paper presents a high statistics measurement of $\phi\to\mu\mu$ with the specific objective to provide insight on the $\phi$ puzzle, i.e. the difference in the inverse $T$ slopes and absolute yields measured by NA49 and NA50 in the kaon and lepton channel, respectively. Transverse momentum distributions were studied as a function of centrality. The slope parameter $T$ shows a rapid increase with centrality, followed by a saturation. Variations of $T$ with the fit range of the order of 15 MeV were observed, possibly as a consequence of radial flow. The $\phi$ meson yield normalized to the number of participants increases with centrality and is consistently higher than the yield measured by the NA49 experiment at any centrality.Comment: 4 Pages, 2 Figures. Proceedings of the 20$^{th}$ International Conference on Ultra-Relativistic Nucleus Nucleus Collision

Evidence for radial flow of thermal dileptons in high-energy nuclear collisions

The NA60 experiment at the CERN SPS has studied low-mass dimuon production in 158 AGeV In-In collisions. An excess of pairs above the known meson decays has been reported before. We now present precision results on the associated transverse momentum spectra. The slope parameter Teff extracted from the spectra rises with dimuon mass up to the rho, followed by a sudden decline above. While the initial rise is consistent with the expectations for radial flow of a hadronic decay source, the decline signals a transition to an emission source with much smaller flow. This may well represent the first direct evidence for thermal radiation of partonic origin in nuclear collisions.Comment: Accepted for publication in Physical Review Letter

Multiple Statistical Analysis Techniques Corroborate Intratumor Heterogeneity in Imaging Mass Spectrometry Datasets of Myxofibrosarcoma

MALDI mass spectrometry can generate profiles that contain hundreds of biomolecular ions directly from tissue. Spatially-correlated analysis, MALDI imaging MS, can simultaneously reveal how each of these biomolecular ions varies in clinical tissue samples. The use of statistical data analysis tools to identify regions containing correlated mass spectrometry profiles is referred to as imaging MS-based molecular histology because of its ability to annotate tissues solely on the basis of the imaging MS data. Several reports have indicated that imaging MS-based molecular histology may be able to complement established histological and histochemical techniques by distinguishing between pathologies with overlapping/identical morphologies and revealing biomolecular intratumor heterogeneity. A data analysis pipeline that identifies regions of imaging MS datasets with correlated mass spectrometry profiles could lead to the development of novel methods for improved diagnosis (differentiating subgroups within distinct histological groups) and annotating the spatio-chemical makeup of tumors. Here it is demonstrated that highlighting the regions within imaging MS datasets whose mass spectrometry profiles were found to be correlated by five independent multivariate methods provides a consistently accurate summary of the spatio-chemical heterogeneity. The corroboration provided by using multiple multivariate methods, efficiently applied in an automated routine, provides assurance that the identified regions are indeed characterized by distinct mass spectrometry profiles, a crucial requirement for its development as a complementary histological tool. When simultaneously applied to imaging MS datasets from multiple patient samples of intermediate-grade myxofibrosarcoma, a heterogeneous soft tissue sarcoma, nodules with mass spectrometry profiles found to be distinct by five different multivariate methods were detected within morphologically identical regions of all patient tissue samples. To aid the further development of imaging MS based molecular histology as a complementary histological tool the Matlab code of the agreement analysis, instructions and a reduced dataset are included as supporting information

Thermal dileptons at SPS energies

Clear signs of excess dileptons above the known sources were found at the SPS since long. However, a real clarification of these observations was only recently achieved by NA60, measuring dimuons with unprecedented precision in 158A GeV, In-In collisions. The excess mass spectrum in the region M<1 GeV is consistent with a dominant contribution from pi+pi- -> rho -> mu+mu- annihilation. The associated rho spectral function shows a strong broadening, but essentially no shift in mass. In the region M>1 GeV, the excess is found to be prompt, not due to enhanced charm production. The inverse slope parameter Teff associated with the transverse momentum spectra rises with mass up to the rho, followed by a sudden decline above. While the initial rise, coupled to a hierarchy in hadron freeze-out, points to radial flow of a hadronic decay source, the decline above signals a transition to a low-flow source, presumably of partonic origin. The mass spectra show at low transverse momenta the steep rise towards low masses characteristic for Planck-like radiation. The polarization of the excess referred to the Collins Soper frame is found to be isotropic. All observations are consistent with the interpretation of the excess as thermal radiation.Comment: Prepared for 20th International Conference on Ultra-Relativistic Nucleus-Nucleus Collisions: Quark Matter 2008 (QM2008), Jaipur, India, 4-10 Feb. 200

NA60 results on thermal dimuons

The NA60 experiment at the CERN SPS has measured muon pairs with unprecedented precision in 158A GeV In-In collisions. A strong excess of pairs above the known sources is observed in the whole mass region 0.2<M<2.6 GeV. The mass spectrum for M<1 GeV is consistent with a dominant contribution from pi+pi- -> rho -> mu+mu- annihilation. The associated rho spectral function shows a strong broadening, but essentially no shift in mass. For M>1 GeV, the excess is found to be prompt, not due to enhanced charm production, with pronounced differences to Drell-Yan pairs. The slope parameter Teff associated with the transverse momentum spectra rises with mass up to the rho, followed by a sudden decline above. The rise for M<1 GeV is consistent with radial flow of a hadronic emission source. The seeming absence of significant flow for M>1 GeV and its relation to parton-hadron duality is discussed in detail, suggesting a dominantly partonic emission source in this region. A comparison of the data to the present status of theoretical modeling is also contained. The accumulated empirical evidence, including also a Planck-like shape of the mass spectra at low pT and the lack of polarization, is consistent with a global interpretation of the excess dimuons as thermal radiation. We conclude with first results on omega in-medium effects.Comment: 10 pages, 12 figures, submitted to Eur. Phys. J.

Study of the electromagnetic transition form-factors in \eta -> \mu^+\mu^-\gamma and \omega -> \mu^+\mu^-\pi^0 decays with NA60

The NA60 experiment at the CERN SPS has studied low-mass muon pairs in 158A GeV In-In collisions. The mass and pT spectra associated with peripheral collisions can quantitatively be described by the known neutral meson decays. The high data quality has allowed to remeasure the electromagnetic transition form factors of the Dalitz decays \eta -> \mu^+\mu^-\gamma and \omega -> \mu^+\mu^-\pi^0. Using the usual pole approximation F = (1-M_{\mu\mu}^{2}/\Lambda^{2})^{-1} for the form factors, we find \Lambda^{-2} (in GeV^{-2}) to be 1.95+-0.17(stat.)+-0.05(syst.) for the \eta and 2.24+-0.06(stat.)+-0.02(syst.) for the \omega. While the values agree with previous results from the Lepton-G experiment, the errors are greatly improved, confirming now on the level of 10\sigma the strong enhancement of the \omega form factor beyond the expectation from vector meson dominance. An improved value of the branching ratio BR(\omega -> \mu^+\mu^-\pi^0) = [1.73+-0.25(stat.)+-0.14(syst.)]*10^{-4} has been obtained as a byproduct.Comment: Submitted to Phys. Lett.

J/psi azimuthal anisotropy relative to the reaction plane in Pb-Pb collisions at 158 GeV per nucleon

The J/$\psi$ azimuthal distribution relative to the reaction plane has been measured by the NA50 experiment in Pb-Pb collisions at 158 GeV/nucleon. Various physical mechanisms related to charmonium dissociation in the medium created in the heavy ion collision are expected to introduce an anisotropy in the azimuthal distribution of the observed J/$\psi$ mesons at SPS energies. Hence, the measurement of J/$\psi$ elliptic anisotropy, quantified by the Fourier coefficient v$_2$ of the J/$\psi$ azimuthal distribution relative to the reaction plane, is an important tool to constrain theoretical models aimed at explaining the anomalous J/$\psi$ suppression observed in Pb-Pb collisions. We present the measured J/$\psi$ yields in different bins of azimuthal angle relative to the reaction plane, as well as the resulting values of the Fourier coefficient v$_{2}$ as a function of the collision centrality and of the J/$\psi$ transverse momentum. The reaction plane has been estimated from the azimuthal distribution of the neutral transverse energy detected in an electromagnetic calorimeter. The analysis has been performed on a data sample of about 100 000 events, distributed in five centrality or p$_{\rm T}$ sub-samples. The extracted v$_{2}$ values are significantly larger than zero for non-central collisions and are seen to increase with p$_{\rm T}$.Comment: proceedings of HP08 conference corrected a typo in one equatio

Hydration of dicalcium silicate and diffusion through neo-formed calcium-silicate-hydrates at weathered surfaces control the long-term leaching behaviour of basic oxygen furnace (BOF) steelmaking slag

Alkalinity generation and toxic trace metal (such as vanadium) leaching from basic oxygen furnace (BOF) steel slag particles must be properly understood and managed by pre-conditioning if beneficial reuse of slag is to be maximised. Water leaching under aerated conditions was investigated using fresh BOF slag at three different particle sizes (0.5–1.0, 2–5 and 10 × 10 × 20 mm blocks) and a 6-month pre-weathered block. There were several distinct leaching stages observed over time associated with different phases controlling the solution chemistry: (1) free-lime (CaO) dissolution (days 0–2); (2) dicalcium silicate (Ca₂SiO₄) dissolution (days 2–14) and (3) Ca–Si–H and CaCO₃ formation and subsequent dissolution (days 14–73). Experiments with the smallest size fraction resulted in the highest Ca, Si and V concentrations, highlighting the role of surface area in controlling initial leaching. After ~2 weeks, the solution Ca/Si ratio (0.7–0.9) evolved to equal those found within a Ca–Si–H phase that replaced dicalcium silicate and free-lime phases in a 30- to 150-μm altered surface region. V release was a two-stage process; initially, V was released by dicalcium silicate dissolution, but V also isomorphically substituted for Si into the neo-formed Ca–Si–H in the alteration zone. Therefore, on longer timescales, the release of V to solution was primarily controlled by considerably slower Ca–Si–H dissolution rates, which decreased the rate of V release by an order of magnitude. Overall, the results indicate that the BOF slag leaching mechanism evolves from a situation initially dominated by rapid hydration and dissolution of primary dicalcium silicate/free-lime phases, to a slow diffusion limited process controlled by the solubility of secondary Ca–Si–H and CaCO₃ phases that replace and cover more reactive primary slag phases at particle surfaces