Relationship between Semi-Quantitative Parameters of Thallium-201 Myocardial Perfusion Imaging and Coronary Artery Disease.

This study aimed to investigate the diagnostic performance of semi-quantitative parameters of thallium-201 myocardial perfusion imaging (MPI) for coronary artery disease (CAD). From January to December 2017, patients were enrolled who had undergone Tl-201 MPI and received cardiac catheterization for coronary artery disease within three months of MPI. Receiver operating characteristics (ROC) analysis was used to determine the optimal cutoff values of semi-quantitative parameters. A comparison of the sensitivity and specificity of these parameters based on different subgroupings was further performed. A total of 130 patients were enrolled for further analysis. Among the collected parameters, the stress total perfusion deficit (sTPD) had the highest value of the area under curve (0.813) under the optimal cutoff value of 3.5%, with a sensitivity and specificity of 73.5% and 74.5%, respectively (p = 0.0000), for the diagnosis of CAD. With further subgrouping analysis based on history of diabetes or dyslipidemia, the sensitivity and specificity showed similar results. Based on the currently collected data and image acquisition conditions, the sTPD parameter has a clinical role for the diagnosis of CAD with a cutoff value of 3.5%.

Detection of transient infrared absorption of SO3 and 1,3,2-dioxathietane-2,2-dioxide [cyc-(CH2)O(SO2)O] in the reaction CH2OO+SO2.

We recorded time-resolved infrared absorption spectra of transient species produced on irradiation at 308 nm of a flowing mixture of CH2I2/O2/N2/SO2 at 298 K. Bands of CH2OO were observed initially upon irradiation; their decrease in intensity was accompanied by the appearance of an intense band at 1391.5 cm-1 that is associated with the degenerate SO-stretching mode of SO3, two major bands of HCHO at 1502 and 1745 cm-1, and five new bands near >1340, 1225, 1100, 940, and 880 cm-1. The band near 1340 cm-1 was interfered by absorption of SO2 and SO3, so its band maximum might be greater than 1340 cm-1. SO3 in its internally excited states was produced initially and became thermalized at a later period. The rotational contour of the band of thermalized SO3 agrees satisfactorily with the reported spectrum of SO3. These five new bands are tentatively assigned to an intermediate 1,3,2-dioxathietane-2,2-dioxide [cyc-(CH2)O(SO2)O] according to comparison with anharmonic vibrational wavenumbers and relative IR intensities predicted for this intermediate. Observation of a small amount of cyc-(CH2)O(SO2)O is consistent with the expected reaction according to the potential energy scheme predicted previously. SO3+HCHO are the major products of the title reaction. The other predicted product channel HCOOH+SO2 was unobserved and its branching ratio was estimated to be <5%.

Infrared absorption of methanol-water clusters (CH3OH)n(H2O), n = 1-4, recorded with the VUV-ionization/IR-depletion technique.

We recorded infrared (IR) spectra in the CH- and OH-stretching regions of size-selected clusters of methanol (M) with one water molecule (W), represented as MnW, n = 1-4, in a pulsed supersonic jet using the photoionization/IR-depletion technique. Vacuum ultraviolet emission at 118 nm served as the source of ionization in a time-of-flight mass spectrometer to detect clusters MnW as protonated forms Mn-1WH+. The variations in intensities of Mn-1WH+ were monitored as the wavelength of the IR laser light was tuned across the range 2700-3800 cm-1. IR spectra of size-selected clusters were obtained on processing of the observed action spectra of the related cluster-ions according to a mechanism that takes into account the production and loss of each cluster due to IR photodissociation. Spectra of methanol-water clusters in the OH region show significant variations as the number of methanol molecules increases, whereas those in the CH region are similar for all clusters. Scaled harmonic vibrational wavenumbers and relative IR intensities predicted with the M06-2X/aug-cc-pVTZ method for the methanol-water clusters are consistent with our experimental results. For dimers, absorption bands of a structure WM with H2O as a hydrogen-bond donor were observed at 3570, 3682, and 3722 cm-1, whereas weak bands of MW with methanol as a hydrogen-bond donor were observed at 3611 and 3753 cm-1. For M2W, the free OH band of H2O was observed at 3721 cm-1, whereas a broad feature was deconvoluted to three bands near 3425, 3472, and 3536 cm-1, corresponding to the three hydrogen-bonded OH-stretching modes in a cyclic structure. For M3W, the free OH shifted to 3715 cm-1, and the hydrogen-bonded OH-stretching bands became much broader, with a weak feature near 3179 cm-1 corresponding to the symmetric OH-stretching mode of a cyclic structure. For M4W, the observed spectrum agrees unsatisfactorily with predictions for the most stable cyclic structure, indicating significant contributions from branched isomers, which is distinctly different from M5 of which the cyclic form dominates.

Evidence of preserved collagen in an Early Jurassic sauropodomorph dinosaur revealed by synchrotron FTIR microspectroscopy.

Fossilized organic remains are important sources of information because they provide a unique form of biological and evolutionary information, and have the long-term potential for genomic explorations. Here we report evidence of protein preservation in a terrestrial vertebrate found inside the vascular canals of a rib of a 195-million-year-old sauropodomorph dinosaur, where blood vessels and nerves would normally have been present in the living organism. The in situ synchrotron radiation-based Fourier transform infrared (SR-FTIR) spectra exhibit the characteristic infrared absorption bands for amide A and B, amide I, II and III of collagen. Aggregated haematite particles (α-Fe2O3) about 6∼8 µm in diameter are also identified inside the vascular canals using confocal Raman microscopy, where the organic remains were preserved. We propose that these particles likely had a crucial role in the preservation of the proteins, and may be remnants partially contributed from haemoglobin and other iron-rich proteins from the original blood.

Infrared spectral identification of the Criegee intermediate (CH3)2COO.

Criegee intermediates are carbonyl oxides that play critical roles in the ozonolysis of alkenes in the atmosphere. So far, the infrared spectra of only the simplest Criegee intermediates CH2OO and CH3CHOO are reported. We report the transient infrared spectrum of the next member (CH3)2COO, produced from ultraviolet irradiation of a mixture of (CH3)2CI2 + O2 in a flow reactor and detected with a step-scan Fourier-transform spectrometer. The four observed bands near 1424, 1368, 1040, and 887.4 cm-1 provide definitive identification of (CH3)2COO. The observed vibrational wavenumbers and rotational contours agree with those predicted with quantum-chemical calculations; contributions of the hot bands from excited states of the low-lying torsional modes are significant. The rapid decay yields an estimate of the rate coefficient ∼1.6 × 10-10 cm3 molecule-1 s-1 for the self-reaction of (CH3)2COO. The direct IR detection of (CH3)2COO should prove useful for field measurements and laboratory investigations of related Criegee mechanism.

Controlling stimulated coherent spectroscopy and microscopy by a position-dependent phase.

We study the role of geometry dependent phase shifts in stimulated coherent spectroscopy, a special class of heterodyne optical spectroscopy techniques. We generalize the theoretical description of stimulated spectroscopy to include spatial phase effects, and consider the measured material response for several representative excitation and detection configurations. Using stimulated Raman scattering microscopy as an example, we show that different components of the material response are measured depending the position of the object in focus. We discuss the implications of the position dependent phase in stimulated coherent microscopy and point out a detection configuration in which its effects are minimized.

Mapping molecular orientation with phase sensitive vibrationally resonant sum-frequency generation microscopy.

We demonstrate a phase sensitive, vibrationally resonant sum-frequency generation (PSVR-SFG) microscope that combines high resolution, fast image acquisition speed, chemical selectivity, and phase sensitivity. Using the PSVR-SFG microscope, we generate amplitude and phase images of the second-order susceptibility of collagen I fibers in rat tail tendon tissue on resonance with the methylene vibrations of the protein. We find that the phase of the second-order susceptibility shows dependence on the effective polarity of the fibril bundles, revealing fibrous collagen domains of opposite orientations within the tissue. The presence of collagen microdomains in tendon tissue may have implications for the interpretation of the mechanical properties of the tissue.

Biomolecular imaging with coherent nonlinear vibrational microscopy.

Optical imaging with spectroscopic vibrational contrast is a label-free solution for visualizing, identifying, and quantifying a wide range of biomolecular compounds in biological materials. Both linear and nonlinear vibrational microscopy techniques derive their imaging contrast from infrared active or Raman allowed molecular transitions, which provide a rich palette for interrogating chemical and structural details of the sample. Yet nonlinear optical methods, which include both second-order sum-frequency generation (SFG) and third-order coherent Raman scattering (CRS) techniques, offer several improved imaging capabilities over their linear precursors. Nonlinear vibrational microscopy features unprecedented vibrational imaging speeds, provides strategies for higher spatial resolution, and gives access to additional molecular parameters. These advances have turned vibrational microscopy into a premier tool for chemically dissecting live cells and tissues. This review discusses the molecular contrast of SFG and CRS microscopy and highlights several of the advanced imaging capabilities that have impacted biological and biomedical research.

Fate of intravenously administered gold nanoparticles in hair follicles: follicular delivery, pharmacokinetic interpretation, and excretion.

Gold nanoparticles (GNPs) are intravenously administered to mice. Deposition at the pilosebacious unit and whiskers is visualized with X-ray fluorescence after 30 minutes and 14 days. After 30 minutes the dermal papilla, bulge region, and root sheath all contain NPs. GNPs are driven externally out from follicles, counteractive to transfollicular delivery. After 14 days, gold bands in hairs reflect pharmacokinetic profiles indicating blood concentration kinetics. Elimination rate constants infer half-lives from 3 hairs from an individual mouse within reasonable agreement (6.08, 7.15, and 8.66 hours). 3D reconstruction of NP distributions with confocal microscopy identifies aggregates within the medullary canal. Intermittent NP deposition continues randomly over the two week period demonstrating prolonged NP mobility in vivo. NPs are still retained at the hair bulb after 14 days. The observations further account for the excretory mechanisms of NPs and their behavior in the pilosebacous unit, and demonstrate monitoring pharmacokinetic behavior in individual animals.

Probing the dynamics of doxorubicin-DNA intercalation during the initial activation of apoptosis by fluorescence lifetime imaging microscopy (FLIM).

Doxorubicin is a potent anthracycline antibiotic, commonly used to treat a wide range of cancers. Although postulated to intercalate between DNA bases, many of the details of doxorubicin's mechanism of action remain unclear. In this work, we demonstrate the ability of fluorescence lifetime imaging microscopy (FLIM) to dynamically monitor doxorubicin-DNA intercalation during the earliest stages of apoptosis. The fluorescence lifetime of doxorubicin in nuclei is found to decrease rapidly during the first 2 hours following drug administration, suggesting significant changes in the doxorubicin-DNA binding site's microenvironment upon apoptosis initiation. Decreases in doxorubicin fluorescence lifetimes were found to be concurrent with increases in phosphorylation of H2AX (an immediate signal of DNA double-strand breakage), but preceded activation of caspase-3 (a late signature of apoptosis) by more than 150 minutes. Time-dependent doxorubicin FLIM analyses of the effects of pretreating cells with either Cyclopentylidene-[4-(4-chlorophenyl)thiazol-2-yl)-hydrazine (a histone acetyltransferase inhibitor) or Trichostatin A (a histone deacetylase inhibitor) revealed significant correlation of fluorescence lifetime with the stage of chromatin decondensation. Taken together, our findings suggest that monitoring the dynamics of doxorubicin fluorescence lifetimes can provide valuable information during the earliest phases of doxorubicin-induced apoptosis; and implicate that FLIM can serve as a sensitive, high-resolution tool for the elucidation of intercellular mechanisms and kinetics of anti-cancer drugs that bear fluorescent moieties.

Characterization of cholesterol crystals in atherosclerotic plaques using stimulated Raman scattering and second-harmonic generation microscopy.

Cholesterol crystals (ChCs) have been identified as a major factor of plaque vulnerability and as a potential biomarker for atherosclerosis. Yet, due to the technical challenge of selectively detecting cholesterol in its native tissue environment, the physiochemical role of ChCs in atherosclerotic progression remains largely unknown. In this work, we demonstrate the utility of hyperspectral stimulated Raman scattering (SRS) microscopy combined with second-harmonic generation (SHG) microscopy to selectively detect ChC. We show that despite the polarization sensitivity of the ChC Raman spectrum, cholesterol monohydrate crystals can be reliably discriminated from aliphatic lipids, from structural proteins of the tissue matrix and from other condensed structures, including cholesteryl esters. We also show that ChCs exhibit a nonvanishing SHG signal, corroborating the noncentrosymmetry of the crystal lattice composed of chiral cholesterol molecules. However, combined hyperspectral SRS and SHG imaging reveals that not all SHG-active structures with solidlike morphologies can be assigned to ChCs. This study exemplifies the merit of combining SRS and SHG microscopy for an enhanced label-free chemical analysis of crystallized structures in diseased tissue.

Respiratory-inductive-plethysmography-derived flow can be a useful clinical tool to detect patients with obstructive sleep apnea syndrome.

BACKGROUND/PURPOSE: Obstructive sleep apnea (OSA) is a common disorder characterized by recurrent episodes of a complete or partial collapse of the upper airway during sleep. The disease is traditionally diagnosed by overnight polysomnography with detection flow limitation by nasal pressure cannulas. The aim of this study was to evaluate the accuracy of flow (X flow) from calibrated respiratory inductive plethysmography. METHODS: We studied 60 male and 26 female patients who came to our sleep center in 2007. All the participants received overnight polysomnography and data were graded blindly and randomly by two experienced technicians. RESULTS: Patients with OSA were predominantly male, with higher body mass index, higher percentage of snorers, and more events of oxygen desaturation and arousal than those without OSA. There was a good correlation of X flow and flow from nasal pressure cannulas, regardless of total apnea-hypopnea, apnea or hypopnea events. The correlation was especially strong in severe OSA patients. The sensitivity and specificity to find OSA (apnea-hypopnea index ≥5) from X flow versus standard polysomnography was 98% and 100%, respectively. Positive predictive value was 100% and negative predictive value was 97%. CONCLUSION: X flow could be a good clinical tool to be used instead of flow from nasal pressure cannulas in OSA patients.

Probing the binding kinetics of proinflammatory cytokine-antibody interactions using dual color fluorescence cross correlation spectroscopy.

Dual color fluorescence cross correlation spectroscopy (FCCS) was used to investigate quantitatively the binding kinetics of tumor necrosis factor (TNFα) with TNFα antibody (anti-TNFα) following fluorescent labeling. Through the analysis of the auto correlation curves of fluorescence correlation spectroscopy (FCS), diffusion coefficients of 100.06 ± 4.9 µm(2) s(-1) and 48.96 ± 2.52 µm(2) s(-1) for Alexa488-TNFα and Atto647N-anti-TNFα were obtained. In addition, the calculated hydrodynamic diameters of the Alexa488-TNFα and Atto647N-anti-TNFα were approximately 4.89 ± 0.24 nm and 9.99 ± 0.52 nm, respectively, which agrees with the values of 5.20 ± 1.23 nm and 9.28 ± 0.86 nm for the native TNFα and the anti-TNFα as determined from dynamic light scattering measurements. For the binding kinetics, association (k(on)) and dissociation (k(off)) rate constants were (1.13 ± 0.08) × 10(4) M(-1) s(-1) and (1.53 ± 0.19) × 10(-3) s(-1) while the corresponding dissociation constant (K(d)) at 25 °C was (1.36 ± 0.10) × 10(-7) M. We believe this is the first report on the binding kinetics for TNFα-antibody recognition in the homogeneous phase. Using this technology, we have shown that controlled experiments can be performed to gain insight into molecular mechanisms involved in the immune response.

Coherent anti-Stokes Raman scattering microscopy using a single-pass picosecond supercontinuum-seeded optical parametric amplifier.

We have demonstrated coherent anti-Stokes Raman scattering (CARS) microscopy with a single-pass picosecond supercontinuum-seeded optical parametric amplifier (SCOPA). The SCOPA was pumped by a frequency-doubled picosecond passively mode-locked Nd:YVO(4) laser, and was seeded by a supercontinuum light source. Compared with the conventional experimental setups of CARS microscopy, our exposition is substantially simpler because the pump and Stokes lasers are overlapped in the SCOPA automatically and thus steered into a microscope coherently. The feasibility of this novel light source to CARS imaging was illustrated by acquiring the fundamental and overtone CARS images of the aromatic C-H stretching mode of polystyrene beads and an image of the pharynx of a C. elegans of the aliphatic C-H stretching mode.

Rovibronic bands of the A<--X transition of CH3OO and CD3OO detected with cavity ringdown absorption near 1.2-1.4 microm.

We have recorded several rovibronic bands of CH3OO and CD3OO in their A<--X transitions in the range of 1.18-1.40 microm with the cavity ringdown technique. While the electronic origins for these species have been reported previously, many newly observed rovibronic bands are described here. The experimental vibrational frequencies (given as nu in the unit cm(-1) in this paper) for the COO bending (nu8) and COO symmetric stretching (nu7) modes in the A state are 378 and 887 cm(-1) for CH3OO, and 348 and 824 cm(-1) for CD3OO, respectively. In addition, two other vibrational frequencies were observed for the A state of CD3OO, namely, nu5 (954 cm(-1)) and nu6 (971 cm(-1)). These experimental vibrational frequencies for the A state of both CH3OO and CD3OO are in good agreement with predictions from quantum-chemical calculations at the UB3LYP/aug-cc-pVTZ level. The enhanced activity of the nu5 vibrational mode in CD3OO is rationalized by mode mixing with the nu7 mode, as supported by calculations of multidimensional Franck-Condon factors. In addition, many hot bands involving the methyl torsional mode (nu12) are observed for both normal and deuterated methyl peroxy. These bands include the "typical" sequence transitions and some "atypical" ones due to the nature of the eigenvalues and eigenfunctions which are a consequence of the low, but very different, torsional barriers in the X and A states. In addition, the 12(2)2 band in CH3OO and the 12(3)3 band in CD3OO show quite different structures than the origin bands, an effect which results from tunneling splittings comparable to the rotational contour.

Detection of vibration-rotational band 5-0 of 12C16O X 1sigma+ with cavity ringdown absorption near 0.96 microm.

We have recorded extremely weak absorption in the overtone band 5-0 of 12C16O X 1sigma+ near 0.96 microm with cavity ringdown spectroscopy; the light source was a Raman-shifted dye laser pumped with a frequency-doubled Nd:YAG laser. This band shows lines in branch P to be much more intense than corresponding lines in branch R, in contrast to all lower overtone bands v-0 (v = 1-4). This reversal in relative intensity is explained quantitatively in terms of a radial function for the electric dipolar moment of CO. We have estimated absorption line strengths for P3-P18 in band 5-0 of 12C16O; these strengths are consistent with a pure vibrational matrix element <5/p(x)/0> = (3.6 +/- 0.3) x 10(-36) C m of the electric dipolar moment p(x), a Herman-Wallis coefficient C0(5) of about -0.1, and a band strength of (5.1 +/- 1.3) x 10(-29) m at 293 K.

Quantitative spectroscopic and theoretical study of the optical absorption spectra of H2O, HOD, and D2O in the 125-145 nm region.

The room temperature absorption spectra of water and its isotopomers D2O and HOD have been determined in absolute cross section units in the 125 to 145 nm wavelength region using synchrotron radiation. The experimental results for these B band spectra are compared with results from quantum mechanical calculations using accurate diabatic ab initio potentials. A Monte Carlo sampling over the initial rotational states of the molecules is applied in order to calculate the cross sections at a temperature of 300 K. The overall rotation of the water molecule is treated exactly. Both for the experimental and for the theoretical spectrum an analysis is made in terms of a component attributed to rapid direct dissociation processes and a component attributed to longer-lived resonances. The agreement between the results from experiment and theory is excellent for H2O and D2O. In the case of HOD in the results of theory two more resonances are found at low energy. It is demonstrated that the width of the resonances of 0.04 eV is the result of overlapping and somewhat narrower resonances in the spectra of molecules differing in rotational ground state.

Infrared cavity ringdown spectroscopy of jet-cooled polycyclic aromatic hydrocarbons.

Infrared absorption spectra of the CH stretching region were observed for naphthalene, anthracene, phenanthrene, pyrene, and perylene using a heated, supersonic, slit-jet source and cavity ringdown spectroscopy. Band positions and intensities recorded with 0.2-cm-1 resolution were compared with previous gas-phase and argon matrix isolation experiments, as well as theoretical calculations. The largest matrix shift in the absorption maximum (-7.4 cm-1) was observed for anthracene, with all others shifted by 3.0 cm-1 or less. Spectral features in the supersonic jet spectrum were generally narrower than those observed in the Ar matrix, with the largest matrix broadening found for the perylene (80% increase). Low number densities observed for the larger polycyclic aromatic hydrocarbons (PAHs) suggest that the lower vapor pressure of PAHs with catacondensed four-membered rings and with five-membered rings other than perylene will not be detectable using our current configuration.