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The inherently low signal-to-noise ratio of NMR and MRI is now being addressed by hyperpolarization methods. For example, iridium-based catalysts that reversibly bind both parahydrogen and ligands in solution can hyperpolarize protons (SABRE) or heteronuclei (X-SABRE) on a wide variety of ligands, using a complex interplay of spin dynamics and chemical exchange processes, with common signal enhancements between 103 and 104 . This does not approach obvious theoretical limits, and further enhancement would be valuable in many applications (such as imaging mM concentration species in vivo). Most SABRE/X-SABRE implementations require far lower fields (μT-mT) than standard magnetic resonance (>1T), and this gives an additional degree of freedom: the ability to fully modulate fields in three dimensions. However, this has been underexplored because the standard simplifying theoretical assumptions in magnetic resonance need to be revisited. Here, we take a different approach, an evolutionary strategy algorithm for numerical optimization, multi-axis computer-aided heteronuclear transfer enhancement for SABRE (MACHETE-SABRE). We find nonintuitive but highly efficient multiaxial pulse sequences which experimentally can produce a sevenfold improvement in polarization over continuous excitation. This approach optimizes polarization differently than traditional methods, thus gaining extra efficiency. [ABSTRACT FROM AUTHOR]

The spatial heterogeneity of carrier dynamics in mixed halide perovskite CH3NH3PbI3−xClx thin films with a range of different chloride additions is mapped using femtosecond transient absorption microscopy (TAM). The comparison of TAM images of fibrous and granular polycrystalline CH3NH3PbI3−xClx films indicates that the impact of chloride addition on the local heterogeneity of carrier dynamics is highly dependent on the film preparation method and the resulting morphology. In addition to signals of pristine CH3NH3PbI3, CH3NH3PbI3−xClx films with a fibrous structure show long-lived excited state absorption (ESA) signals in localized, microscopic regions. The ESA signal exhibits transient absorption with a rise time of about 5 ps after the excitation pulse, indicating that these distinct micrograins have preferential carrier trapping properties. The chemical composition of these micrograins does not differ detectably from their surroundings. In contrast, in CH3NH3PbI3−xClx films with a granular structure, Cl addition does not seem to affect the charge carrier dynamics. These results provide insight into the localized effects of halide mixing and on the resulting photophysical properties of mixed halide perovskite materials on the micrometer length scale. [ABSTRACT FROM AUTHOR]

Signal Amplification By Reversible Exchange (SABRE) and its heteronuclear variant SABRE in SHield Enables Alignment Transfer to Heteronuclei create large nuclear magnetization in target ligands, exploiting level crossings in an iridium catalyst that transiently binds both the ligands and parahydrogen. This requires a specific, small magnetic field to match Zeeman splittings to scalar couplings. Here, we explore a different strategy, direct creation of heteronuclear singlet states in the target ligands, which produces enhanced signals at other field strengths, including zero field. We also show that pulsed methods (including pulsed field nulling) coherently and selectively pump such singlets, affording a significant enhancement on the resulting hyperpolarization. [ABSTRACT FROM AUTHOR]

SABRE (Signal Amplification by Reversible Exchange) methods provide a simple, fast, and cost-effective method to hyperpolarize a wide variety of molecules in solution, and have been demonstrated with protons and, more recently, with heteronuclei (X-SABRE). Here, we present several oscillating pulse sequences that use magnetic fields far away from the resonance condition of continuous excitation and can commonly triple the polarization. An analysis with average Hamiltonian theory indicates that the oscillating pulse, in effect, adjusts the J-couplings between hydrides and target nuclei and that a much weaker coupling produces maximum polarization. This theoretical treatment, combined with simulations and experiment, shows substantial magnetization improvements relative to traditional X-SABRE methods. It also shows that, in contrast to most pulse sequence applications, waveforms with reduced time symmetry in the toggling frame make magnetization generation more robust to experimental imperfections. [ABSTRACT FROM AUTHOR]

Hyperpolarization methods in magnetic resonance overcome sensitivity limitations, especially for low-γ nuclei such as 13C and 15N. Signal Amplification By Reversible Exchange (SABRE) and extended SABRE (X-SABRE) are efficient and low-cost methods for generating large polarizations on a variety of nuclei, but they most commonly use low magnetic fields (μT–mT). High field approaches, where hyperpolarization is generated directly in the spectrometer, are potentially much more convenient but have been limited to selectively hyperpolarize single targets. Here we introduce a new pulse sequence-based approach that affords broadband excitation of SABRE hyperpolarization at high magnetic fields without having to tailor pulse sequence parameters to specific targets. This permits simultaneous hyperpolarization of multiple targets for the first time at high field and offers a direct approach to integration of high-field SABRE hyperpolarization into routine NMR applications, such as NMR-based metabonomics and biomolecular NMR. [ABSTRACT FROM AUTHOR]

In this paper we elucidate, theoretically and experimentally, molecular motifs which permit Long- Lived Polarization Protected by Symmetry (LOLIPOPS). The basic assembly principle starts from a pair of chemically equivalent nuclei supporting a long-lived singlet state and is completed by coupling to additional pairs of spins. LOLIPOPS can be created in various sizes; here we review fourspin systems, introduce a group theory analysis of six-spin systems, and explore eight-spin systems by simulation. The focus is on AA'XnX'n spin systems, where typically the A spins are 15N or 13C and X spins are protons. We describe the symmetry of the accessed states, we detail the pulse sequences used to access these states, we quantify the fraction of polarization that can be stored as LOLIPOPS, we elucidate how to access the protected states from A or from X polarization and we examine the behavior of these spin systems upon introduction of a small chemical shift difference. [ABSTRACT FROM AUTHOR]

Here we report on chelating ligands for Signal Amplification By Reversible Exchange (SABRE) catalysts that permit hyperpolarisation on otherwise sterically hindered substrates. We demonstrate 1H enhancements of ∼100-fold over 8.5 T thermal for 2-substituted pyridines, and smaller, yet significant enhancements for provitamin B6 and caffeine. We also show 15N-enhancements of ∼1000-fold and 19F-enhancements of 30-fold. [ABSTRACT FROM AUTHOR]

A recent quantum computing paper (G. S. Uhrig, Phys. Rev. Lett. 98, 100504 (2007)) analytically derived optimal pulse spacings for a multiple spin echo sequence designed to remove decoherence in a two-level system coupled to a bath. The spacings in what has been called a “Uhrig dynamic decoupling (UDD) sequence” differ dramatically from the conventional, equal pulse spacing of a Carr–Purcell–Meiboom–Gill (CPMG) multiple spin echo sequence. The UDD sequence was derived for a model that is unrelated to magnetic resonance, but was recently shown theoretically to be more general. Here we show that the UDD sequence has theoretical advantages for magnetic resonance imaging of structured materials such as tissue, where diffusion in compartmentalized and microstructured environments leads to fluctuating fields on a range of different time scales. We also show experimentally, both in excised tissue and in a live mouse tumor model, that optimal UDD sequences produce different T2-weighted contrast than do CPMG sequences with the same number of pulses and total delay, with substantial enhancements in most regions. This permits improved characterization of low-frequency spectral density functions in a wide range of applications. [ABSTRACT FROM AUTHOR]

Fundamental optical and structural properties of melanins are not well understood due to their poor solubility characteristics and the chemical disorder present during biomolecular synthesis. We apply nonlinear transient absorption spectroscopy to quantify molar absorptivities for eumelanin and pheomelanin and thereby get an estimate for their average pigment sizes. We determine that pheomelanin exhibits a larger molar absorptivity at near IR wavelengths (750 nm), which may be extended to shorter wavelengths. Using the molar absorptivities, we estimate that melanin pigments contain ∼46 and 28 monomer units for eumelanin and pheomelanin, respectively. This is considerably larger than the oligomeric species that have been recently proposed to account for the absorption spectrum of eumelanin and illustrates that larger pigments comprise a significant fraction of the pigment distribution. [ABSTRACT FROM AUTHOR]

In this paper the authors compare 400 nm one-photon and 800 nm two-photon two-dimensional Fourier transform electronic spectra of the organic laser dye Coumarin 102 in methanol using collinear optical pulse sequences and phase cycling. Results from the two different experiments show differences in the photon echo peak positions and shapes, reflecting differences in the two-photon and one-photon selection rules. [ABSTRACT FROM AUTHOR]

Turbulent spin dynamics arising from the joint action of radiation damping and the distant dipolar field are shown to generate irreproducible measurements in popular high-field, gradient-based magnetic resonance (MR) experiments, undermining the prevailing assumption of essentially predictable observables in MR. Sizeable fluctuations in echo amplitudes are reported and numerically simulated for pulsed gradient spin echo and stimulated echo diffusion measurements. The underlying microscopic dynamical instability is characterized by analysis of the finite-time Lyapunov exponents. Perturbations to the modulated magnetization are shown to render magic-angle gradients ineffective in suppressing signal fluctuations. Alternative approaches are suggested for canceling out the feedback interactions leading to spin turbulence. [ABSTRACT FROM AUTHOR]

The effect of pulse propagation on the two-dimensional photon echo (2DPE) spectrum of multilevel systems is investigated using a perturbative method. At high optical densities (OD) peak profiles are broadened asymmetrically, in most cases more strongly along the ω[sub 2] direction than along the ω[sub 1] direction. The amount of broadening is determined both by the OD and by the dynamics of the system. In addition, especially if the different transitions in the system are of unequal strength, the relative intensity of the peaks changes with OD. But even if the transition strengths are the same, the behavior of the cross peaks is different from the diagonal peaks. Since peak shape and relative intensity are important parameters in the interpretation of 2DPE spectra, such OD effects should be taken into account. © 2003 American Institute of Physics. [ABSTRACT FROM AUTHOR]

Artifacts arising from aperiodic turbulent spin dynamics in gradient-based nuclear magnetic resonance (NMR) applications are comprehensively surveyed and numerically simulated by a nonlinear Bloch equation. The unexpected dynamics, triggered by the joint action of radiation damping and the distant dipolar field, markedly deteriorate the performance of certain pulse sequences incorporating weak pulsed-field gradients and long evolution times. The effects are demonstrated in three general classes of gradient NMR applications: solvent signal suppression, diffusion measurements, and coherence pathway selection. Gradient-modulated solvent transverse magnetization can be partially rephased in a series of self-refocusing gradient echoes that blank out solute resonances in the CHESS (chemical-shift-selective spectroscopy) and WATERGATE (gradient-tailored water suppression) solvent suppression schemes. In addition, the discovered dynamics contribute to erratic echo attenuation in pulsed gradient spin echo (PGSE) and PGSE stimulated echo diffusion measurements and produce coherence leakage in gradient-selected DQFCOSY and HMQC experiments. Specific remedies for minimizing unwanted effects are presented. [ABSTRACT FROM AUTHOR]

Studies the multiple spin echo generation by gradients of the radio frequency amplitude using two-dimensional (2D) nuclear magnetic resonance (NMR) nutation spectroscopy and multiple rotary echoes. Principle of 2D NMR nutation spectroscopy; Theory of 2D NMR nutation spectroscopy; Multiple echoes and 2D NMR nutation spectra.

Herein, we demonstrate "direct" 13C hyperpolarization of 13C‐acetate via signal amplification by reversible exchange (SABRE). The standard SABRE homogeneous catalyst [Ir‐IMes; [IrCl(COD)(IMes)], (IMes=1,3‐bis(2,4,6‐trimethylphenyl), imidazole‐2‐ylidene; COD=cyclooctadiene)] was first activated in the presence of an auxiliary substrate (pyridine) in alcohol. Following addition of sodium 1‐13C‐acetate, parahydrogen bubbling within a microtesla magnetic field (i.e. under conditions of SABRE in shield enables alignment transfer to heteronuclei, SABRE‐SHEATH) resulted in positive enhancements of up to ≈100‐fold in the 13C NMR signal compared to thermal equilibrium at 9.4 T. The present results are consistent with a mechanism of "direct" transfer of spin order from parahydrogen to 13C spins of acetate weakly bound to the catalyst, under conditions of fast exchange with respect to the 13C acetate resonance, but we find that relaxation dynamics at microtesla fields alter the optimal matching from the traditional SABRE‐SHEATH picture. Further development of this approach could lead to new ways to rapidly, cheaply, and simply hyperpolarize a broad range of substrates (e.g. metabolites with carboxyl groups) for various applications, including biomedical NMR and MRI of cellular and in vivo metabolism. [ABSTRACT FROM AUTHOR]

Herein, we demonstrate "direct" 13C hyperpolarization of 13C‐acetate via signal amplification by reversible exchange (SABRE). The standard SABRE homogeneous catalyst [Ir‐IMes; [IrCl(COD)(IMes)], (IMes=1,3‐bis(2,4,6‐trimethylphenyl), imidazole‐2‐ylidene; COD=cyclooctadiene)] was first activated in the presence of an auxiliary substrate (pyridine) in alcohol. Following addition of sodium 1‐13C‐acetate, parahydrogen bubbling within a microtesla magnetic field (i.e. under conditions of SABRE in shield enables alignment transfer to heteronuclei, SABRE‐SHEATH) resulted in positive enhancements of up to ≈100‐fold in the 13C NMR signal compared to thermal equilibrium at 9.4 T. The present results are consistent with a mechanism of "direct" transfer of spin order from parahydrogen to 13C spins of acetate weakly bound to the catalyst, under conditions of fast exchange with respect to the 13C acetate resonance, but we find that relaxation dynamics at microtesla fields alter the optimal matching from the traditional SABRE‐SHEATH picture. Further development of this approach could lead to new ways to rapidly, cheaply, and simply hyperpolarize a broad range of substrates (e.g. metabolites with carboxyl groups) for various applications, including biomedical NMR and MRI of cellular and in vivo metabolism. [ABSTRACT FROM AUTHOR]

Diazirine moieties are chemically stable and have been incorporated into biomolecules without impediment of biological activity. The 15N2 labeled diazirines are appealing motifs for hyperpolarization supporting relaxation protected states with long‐lived lifetimes. The (‐CH15N2) diazirine groups investigated here are analogues to methyl groups, which provides the opportunity to transfer polarization stored on a relaxation protected (‐CH15N2) moiety to 1H, thus combining the advantages of long lifetimes of 15N polarization with superior sensitivity of 1H detection. Despite the proximity of 1H to 15N nuclei in the diazirine moiety, 15N T1 times of up to (4.6±0.4) min and singlet lifetimes Ts of up to (17.5±3.8) min are observed. Furthermore, we found terminal diazirines to support hyperpolarized 1H2 singlet states in CH2 groups of chiral molecules. The singlet lifetime of 1H singlets is up to (9.2±1.8) min, thus exceeding 1H T1 relaxation time (at 8.45 T) by a factor of ≈100. [ABSTRACT FROM AUTHOR]

Diazirine moieties are chemically stable and have been incorporated into biomolecules without impediment of biological activity. The 15N2 labeled diazirines are appealing motifs for hyperpolarization supporting relaxation protected states with long‐lived lifetimes. The (‐CH15N2) diazirine groups investigated here are analogues to methyl groups, which provides the opportunity to transfer polarization stored on a relaxation protected (‐CH15N2) moiety to 1H, thus combining the advantages of long lifetimes of 15N polarization with superior sensitivity of 1H detection. Despite the proximity of 1H to 15N nuclei in the diazirine moiety, 15N T1 times of up to (4.6±0.4) min and singlet lifetimes Ts of up to (17.5±3.8) min are observed. Furthermore, we found terminal diazirines to support hyperpolarized 1H2 singlet states in CH2 groups of chiral molecules. The singlet lifetime of 1H singlets is up to (9.2±1.8) min, thus exceeding 1H T1 relaxation time (at 8.45 T) by a factor of ≈100. [ABSTRACT FROM AUTHOR]

The NMR hyperpolarization of uniformly 15N‐labeled [15N3]metronidazole is demonstrated by using SABRE‐SHEATH. In this antibiotic, the 15NO2 group is hyperpolarized through spin relays created by 15N spins in [15N3]metronidazole, and the polarization is transferred from parahydrogen‐derived hydrides over six chemical bonds. In less than a minute of parahydrogen bubbling at approximately 0.4 μT, a high level of nuclear spin polarization (P15N) of around 16 % is achieved on all three 15N sites. This product of 15N polarization and concentration of 15N spins is around six‐fold better than any previous value determined for 15N SABRE‐derived hyperpolarization. At 1.4 T, the hyperpolarized state persists for tens of minutes (relaxation time, T1≈10 min). A novel synthesis of uniformly 15N‐enriched metronidazole is reported with a yield of 15 %. This approach can potentially be used for synthesis of a wide variety of in vivo metabolic probes with potential uses ranging from hypoxia sensing to theranostic imaging. [ABSTRACT FROM AUTHOR]

More people die from melanoma after a stage I diagnosis than after a stage IV diagnosis, because the tools available to clinicians do not readily identify which early-stage cancers will be aggressive. Near-infrared pump-probe microscopy detects fundamental differences in melanin structure between benign human moles and melanoma and also correlates with metastatic potential. However, the biological mechanisms of these changes have been difficult to quantify, as many different mechanisms can contribute to the pump-probe signal. We use model systems (sepia, squid, and synthetic eumelanin), cellular uptake studies, and a range of pump and probe wavelengths to demonstrate that the clinically observed effects come from alterations of the aggregated mode from "thick oligomer stacks" to "thin oligomer stacks" (due to changes in monomer composition) and (predominantly) deaggregation of the assembled melanin structure. This provides the opportunity to use pumpprobe microscopy for the detection and study of melanin-associated diseases. [ABSTRACT FROM AUTHOR]

Analyzes additional resonances due to dipolar couplings between distant nuclei in a variety of two-dimensional solution nuclear magnetic resonance. Use of Bloch equations having a mean-field approximation to the demagnetizing field; Link between the peaks and intermolecular multiple-quantum coherence; Prediction of intensities in solution for dipolar effects.

We address the issue of localization of bond energy in a molecule by stopping intramolecular vibrational relaxation (IVR). We show through model calculations that appropriate frequency sweeps permit selective locking over a well-defined range of resonance frequencies, with little excitation outside that range. We also propose a modified version of an adiabatic half passage experiment that will perform photon locking without complications from inhomogeneities or partial excitation of other transitions for a bright state coupled to a finite number of dark states. [ABSTRACT FROM AUTHOR]

It was recently reported that multiple-quantum NMR coherences could apparently be observed in water and other concentrated samples, in direct violation of established theory. These results were previously explained in a dressed-state framework as manifestations of the coupling between the spins and the coil (quantized radiation damping). Here we provide details of previously communicated experimental explorations of these effects [J. Chem. Phys. 96, 1659 (1992)], and we extend these results to multicomponent samples. We observe cross peaks between independent molecules in solution in two-dimensional experiments, including spectra with multiple-quantum coherence transfer echoes; we also demonstrate coherence transfer between solvent and (dilute) solute molecules. However, we show that these intermolecular cross peaks are induced by a mechanism which is local in nature, and thus radiation damping (either classical or quantized) cannot provide the bulk of the explanation for their occurrence. Simulations and analytical results show that the dipolar demagnetizing field can account for many of these surprising effects, although a complete picture must be more complex. [ABSTRACT FROM AUTHOR]

In this paper we investigate the influence of optical density or superradiance on the photon echo decay using the coupled Maxwell–Bloch equations. Our theory applies to optically thick but dilute media, where the transition dipole–dipole interaction between nearby chromophores is negligible, but the far-field interaction is not. Corrections to the (normalized) echo decay in the optically thin limit, INe(tπ)=exp [-4tπ/T2] (tπ and T2 are the interpulse separation times and the coherence relaxation times, respectively), are found by expanding the polarization, excited state population and pulse electric fields in powers of ζ=αz, where α is the inverse Beer’s absorption length, and z is the coordinate along the pulse propagation axis. Numerical solutions for optically thick samples are also presented, and when ζ>1 the normalized echo intensity is found to obey the simple analytic form: INe(tπ)=2 exp [-tπ/T1]-1, when tπ/T1

To present current melanoma diagnosis, staging, prognosis, and treatment algorithms and how recent advances in laser pump-probe microscopy will fill in the gaps in our clinical understanding. Expert opinion and significantly cited articles identified in SCOPUS were used in conjunction with a pubmed database search on Melanoma practice guidelines from the last 10 years. Significant advances in melanoma treatment have been made over the last decade. However, proper treatment algorithm and prognostic information per melanoma stage remain controversial. The next step for providers will involve the identification of patient population(s) that can benefit from recent advances. One method of identifying potential patients is through new laser imaging techniques. Pump-probe laser microscopy has been shown to correctly identify nevi from melanoma and furthermore stratify melanoma by aggressiveness. The recent development of effective adjuvant therapies for melanoma is promising and should be utilized on appropriate patient populations that can potentially be identified using pump-probe laser microscopy. [ABSTRACT FROM AUTHOR]

Diazirines are an attractive class of potential molecular tags for magnetic resonance imaging owing to their biocompatibility and ease of incorporation into a large variety of molecules. As recently reported, 15N2-diazirine can be hyperpolarized by the SABRE-SHEATH method, sustaining both singlet and magnetization states, thus offering a path to long-lived polarization storage. Herein, we show the generality of this approach by illustrating that the diazirine tag alone is sufficient for achieving excellent signal enhancements with long-lasting polarization. Our investigations reveal the critical role of Lewis basic additives, including water, on achieving SABRE-promoted hyperpolarization. The application of this strategy to a 15N2-diazirine-containing choline derivative demonstrates the potential of 15N2-diazirines as molecular imaging tags for biomedical applications. [ABSTRACT FROM AUTHOR]

Diazirines are an attractive class of potential molecular tags for magnetic resonance imaging owing to their biocompatibility and ease of incorporation into a large variety of molecules. As recently reported, 15N2-diazirine can be hyperpolarized by the SABRE-SHEATH method, sustaining both singlet and magnetization states, thus offering a path to long-lived polarization storage. Herein, we show the generality of this approach by illustrating that the diazirine tag alone is sufficient for achieving excellent signal enhancements with long-lasting polarization. Our investigations reveal the critical role of Lewis basic additives, including water, on achieving SABRE-promoted hyperpolarization. The application of this strategy to a 15N2-diazirine-containing choline derivative demonstrates the potential of 15N2-diazirines as molecular imaging tags for biomedical applications. [ABSTRACT FROM AUTHOR]

NMR with thermal polarization requires relatively concentrated samples, particularly for nuclei with low abundance and low gyromagnetic ratios, such as 15N. We expand the substrate scope of SABRE, a recently introduced hyperpolarization method, to allow access to 15N-enriched Schiff bases. These substrates show fractional 15N polarization levels of up to 2 % while having only minimal 1H enhancements. [ABSTRACT FROM AUTHOR]

Purpose Intermolecular multiple quantum coherences (iMQCs) are a source of MR contrast with applications including temperature imaging, anisotropy mapping, and brown fat imaging. Because all applications are limited by signal-to-noise ratio (SNR), we developed a pulse sequence that detects intermolecular zero quantum coherences with improved SNR. Methods A previously developed pulse sequence that detects iMQCs, HOMOGENIZED with off resonance transfer (HOT), was modified with a multi-spin echo spatial encoding scheme (MSE-HOT). MSE-HOT uses a series of refocusing pulses to generate a stack of images that are averaged in postprocessing for higher SNR. MSE-HOT performance was quantified by measuring its temperature accuracy and precision during hyperthermia of ex vivo red bone marrow samples. Results MSE-HOT yielded a three-fold improvement in temperature precision relative to previous pulse sequences. Sources of improved precision were 1) echo averaging and 2) suppression of J-coupling in the methylene protons of fat. MSE-HOT measured temperature change with an accuracy of 0.6°C. Conclusion MSE-HOT improved the temperature accuracy and precision of HOT to a level that is sufficient for hyperthermia of bone marrow. Magn Reson Med 75:1958-1966, 2016. © 2015 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Multiphoton microscopy has rapidly gained popularity in biomedical imaging and materials science because of its ability to provide three-dimensional images at high spatial and temporal resolution even in optically scattering environments. Currently the majority of commercial and home-built devices are based on two-photon fluorescence and harmonic generation contrast. These two contrast mechanisms are relatively easy to measure but can access only a limited range of endogenous targets. Recent developments in fast laser pulse generation, pulse shaping, and detection technology have made accessible a wide range of optical contrasts that utilize multiple pulses of different colors. Molecular excitation with multiple pulses offers a large number of adjustable parameters. For example, in two-pulse pump-probe microscopy, one can vary the wavelength of each excitation pulse, the detection wavelength, the timing between the excitation pulses, and the detection gating window after excitation. Such a large parameter space can provide much greater molecular specificity than existing single-color techniques and allow for structural and functional imaging without the need for exogenous dyes and labels, which might interfere with the system under study. In this review, we provide a tutorial overview, covering principles of pump-probe microscopy and experimental setup, challenges associated with signal detection and data processing, and an overview of applications. [ABSTRACT FROM AUTHOR]

Purpose Red bone marrow metastases are common in breast and prostate cancer patients, but those metastases are currently incurable. Recent developments show that hyperthermia could be a successful treatment for bone metastasis, but thermometry remains difficult or inaccurate in red marrow. Method The technique evaluated in this study measures the evolution frequency of intermolecular zero quantum coherences (iZQCs) between fat and water. The iZQC evolution frequency was mapped linearly to temperature. The temperature accuracy and coherence lifetime of the iZQC method were evaluated against other thermometry methods that are based on localized spectroscopy and multiple gradient echo imaging. Results The temperature coefficient (α) was 9.8 ± 0.7 ppb/°C with the iZQC method and 2 ± 7 ppb/°C with traditional localized spectroscopy. Conclusion Because the accuracy of thermometry is limited by the reproducibility of α between samples, iZQCs provide nearly a 10-fold accuracy improvement in red marrow (0.7 ppb/°C for iZQCs versus 7 ppb/°C for localized spectroscopy.) The iZQC technique in this study will for the first time allow accurate and quantitative thermal imaging of red marrow. Magn Reson Med, 2014. © 2014 Wiley Periodicals, Inc. Magn Reson Med 74:63-70, 2015. © 2014 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

We demonstrate a multimodal approach that combines a pump-probe with confocal reflectance and multiphoton autofluorescence microscopy. Pump-probe microscopy has been proven to be of great value in analyzing thin tissue sections of pigmented lesions, as it produces molecular contrast which is inaccessible by other means. However, the higher optical intensity required to overcome scattering in thick tissue leads to higher-order nonlinearities in the optical response of melanin (e.g., two-photon pump and one-photon probe) that present additional challenges for interpreting the data. We show that analysis of pigment composition in vivo must carefully account for signal terms that are nonlinear with respect to the pump and probe intensities. We find that pump-probe imaging gives useful contrast for pigmented structures over a large range of spatial scales (100 µm to 1 cm), making it a potentially useful tool for tracking the progression of pigmented lesions without the need to introduce exogenous contrast agents. [ABSTRACT FROM AUTHOR]

The lock-in amplifier is a critical component in many different types of experiments, because of its ability to reduce spurious or environmental noise components by restricting detection to a single frequency and phase. One example application is pump-probe microscopy, a multiphoton technique that leverages excited-state dynamics for imaging contrast. With this application in mind, we present here the design and implementation of a high-speed lock-in amplifier on the field-programmable gate array (FPGA) coprocessor of a data acquisition board. The most important advantage is the inherent ability to filter signals based on more complex modulation patterns. As an example, we use the flexibility of the FPGA approach to enable a novel pump-probe detection scheme based on spread-spectrum communications techniques. [ABSTRACT FROM AUTHOR]