Low- and high-frequency vibrations synergistically enhance singlet exciton fission through robust vibronic resonances.

Singlet exciton fission (SEF) is initiated by ultrafast internal conversion of a singlet exciton into a correlated triplet pair [Formula: see text]. The "reaction coordinates" for ultrafast SEF even in archetypal systems such as pentacene thin film remain unclear. Couplings between fast electrons and slow nuclei are ubiquitous across a range of phenomena in chemistry. Accordingly, spectroscopic detection of vibrational coherences in the [Formula: see text] photoproduct motivated investigations into a possible role of vibronic coupling, akin to that reported in several photosynthetic proteins. However, acenes are very different from chlorophylls with 10× larger vibrational displacements upon photoexcitation and low-frequency vibrations modulating intermolecular orbital overlaps. Whether (and if so how) these unique features carry any mechanistic significance for SEF remains a poorly understood question. Accordingly, synthetic design of new molecules aiming to mimic this process across the solar spectrum has broadly relied on tuning electronic couplings. We address this gap and identify previously unrecognized synergistic interplay of vibrations, which in striking contrast to photosynthesis, vitally enhances SEF across a broad, nonselective and, therefore, unavoidable range of vibrational frequencies. We argue that attaching mechanistic significance to spectroscopically observed prominent quantum beats is misleading. Instead, we show that vibronic mixing leads to anisotropic quantum beats and propose readily implementable polarization-based two-dimensional electronic spectroscopy experiments which uniquely distinguish vibrations which drive vibronic mixing and promote SEF, against spectator vibrations simply accompanying ultrafast internal conversion. Our findings introduce crucial ingredients in synthetic design of SEF materials and spectroscopy experiments aiming to decipher mechanistic details from quantum beats.

Rapid scan white light two-dimensional electronic spectroscopy with 100 kHz shot-to-shot detection.

We demonstrate an approach to two-dimensional electronic spectroscopy (2DES) that combines the benefits of shot-to-shot detection at high-repetition rates with the simplicity of a broadband white light continuum input and conventional optical elements to generate phase-locked pump pulse pairs. We demonstrate this through mutual synchronization between the laser repetition rate, the acousto-optical deflector, the pump delay stage, and the CCD line camera, which allows for rapid scanning of pump optical delay synchronously with the laser repetition rate, while the delay stage is moved at a constant velocity. The resulting shot-to-shot detection scheme is repetition rate scalable and only limited by the CCD line rate and the maximum stage velocity. Using this approach, we demonstrate the measurement of an averaged 2DES absorptive spectrum in as much as 1.2 s of continuous sample exposure per 2D spectrum. We achieve a signal-to-noise ratio of 6.8 for optical densities down to 0.05 with 11.6 s of averaging at 100 kHz laser repetition rate. Combining rapid scanning of mechanical delay lines with shot-to-shot detection as demonstrated here provides a viable alternative to acousto-optic pulse shaping approaches that is repetition-rate scalable, has comparable throughput and sensitivity, and minimizes sample exposure per 2D spectrum with promising micro-spectroscopy applications.

High-sensitivity fluorescence-detected multidimensional electronic spectroscopy through continuous pump-probe delay scan.

Fluorescence-detected multidimensional electronic spectroscopy (fMES) promises high sensitivity compared to conventional approaches and is an emerging spectroscopic approach toward combining the advantages of MES with the spatial resolution of a microscope. Here, we present a visible white light continuum-based fMES spectrometer and systematically explore the sensitivity enhancement expected from fluorescence detection. As a demonstration of sensitivity, we report room temperature two-dimensional coherence maps of vibrational quantum coherences in a laser dye at optical densities of ∼2-3 orders of magnitude lower than conventional approaches. This high sensitivity is enabled by a combination of biased sampling along the optical coherence time axes and a rapid scan of the pump-probe waiting time T at each sample. A combination of this approach with acousto-optic phase modulation and phase-sensitive lock-in detection enables measurements of room temperature vibrational wavepackets even at the lowest ODs. Alternative faster data collection schemes, which are enabled by the flexibility of choosing a non-uniform undersampled grid in the continuous T scanning approach, are also demonstrated.

Optimization of spectrally selective 180° radiofrequency pulse timings in J-difference editing (MEGA) of lactate.

PURPOSE: J-Difference editing (MEGA) provides an effective spectroscopic means of selectively measuring low-concentration metabolites having weakly coupled spins. The fractional inphase and antiphase coherences are determined by the radiofrequency (RF) pulses and inter-RF pulse intervals of the sequence. We examined the timings of the spectrally selective editing 180° pulses (E180) in MEGA-PRESS to maximize the edited signal amplitude in lactate at 3T. METHODS: The time evolution of the lactate spin coherences was analytically and numerically calculated for non-volume localized and single-voxel localized MEGA sequences. Single-voxel localized MEGA-PRESS simulations and phantom experiments were conducted for echo time (TE) 60-160 ms and for all possible integer-millisecond timings of the E180 pulses. Optimized E180 timings of 144, 103, and 109 ms TEs, tailored with simulation and phantom data, were tested in brain tumor patients in vivo. Lactate signals, broadened to singlet linewidths (~6 Hz), were compared between simulation, phantom, and in vivo data. RESULTS: Theoretical and experimental data indicated consistently that the MEGA-edited signal amplitude and width are sensitive to the E180 timings. In volume-localized MEGA, the lactate peak amplitudes in E180-on and difference spectra were maximized at specific E180 timings for individual TEs, largely due to the chemical-shift displacement effects. The E180 timings for maximum lactate peak amplitude were different from those of maximum inphase coherence in in vivo linewidth situations. CONCLUSION: In in vivo MEGA editing, the E180 pulse timings can be effectively used for manipulating the inphase and antiphase coherences and increasing the edited signal amplitude, following TE optimization.

Vibronic resonance along effective modes mediates selective energy transfer in excitonically coupled aggregates.

We recently proposed effective normal modes for excitonically coupled aggregates that exactly transform the energy transfer Hamiltonian into a sum of one-dimensional Hamiltonians along the effective normal modes. Identifying physically meaningful vibrational motions that maximally promote vibronic mixing suggested an interesting possibility of leveraging vibrational-electronic resonance for mediating selective energy transfer. Here, we expand on the effective mode approach, elucidating its iterative nature for successively larger aggregates, and extend the idea of mediated energy transfer to larger aggregates. We show that energy transfer between electronically uncoupled but vibronically resonant donor-acceptor sites does not depend on the intermediate site energy or the number of intermediate sites. The intermediate sites simply mediate electronic coupling such that vibronic coupling along specific promoter modes leads to direct donor-acceptor energy transfer, bypassing any intermediate uphill energy transfer steps. We show that the interplay between the electronic Hamiltonian and the effective mode transformation partitions the linear vibronic coupling along specific promoter modes to dictate the selectivity of mediated energy transfer with a vital role of interference between vibronic couplings and multi-particle basis states. Our results suggest a general design principle for enhancing energy transfer through synergistic effects of vibronic resonance and weak mediated electronic coupling, where both effects individually do not promote efficient energy transfer. The effective mode approach proposed here paves a facile route toward four-wavemixing spectroscopy simulations of larger aggregates without severely approximating resonant vibronic coupling.

Spectral fitting strategy to overcome the overlap between 2-hydroxyglutarate and lipid resonances at 2.25 ppm.

PURPOSE: 1 H MRS provides a noninvasive tool for identifying mutations in isocitrate dehydrogenase (IDH). Quantification of the prominent 2-hydroxyglutarate (2HG) resonance at 2.25 ppm is often confounded by the lipid resonance at the same frequency in tumors with elevated lipids. We propose a new spectral fitting approach to separate these overlapped signals, therefore, improving 2HG evaluation. METHODS: TE 97 ms PRESS was acquired at 3T from 42 glioma patients. New lipid basis sets were created, in which the small lipid 2.25-ppm signal strength was preset with reference to the lipid signal at 0.9 ppm, incorporating published fat relaxation data. LCModel fitting using the new lipid bases (Fitting method 2) was conducted along with fitting using the LCModel built-in lipid basis set (Fitting method 1), in which the lipid 2.25-ppm signal is assessed with reference to the lipid 1.3-ppm signal. In-house basis spectra of low-molecular-weight metabolites were used in both fitting methods. RESULTS: Fitting method 2 showed marked improvement in identifying IDH mutational status compared with Fitting method 1. 2HG estimates from Fitting method 2 were overall smaller than those from Fitting method 1, which was because of differential assignment of the signal at 2.25 ppm to lipids. In receiver operating characteristic analysis, Fitting method 2 provided a complete distinction between IDH mutation and wild-type whereas Fitting method 1 did not. CONCLUSION: The data suggest that 1 H MR spectral fitting using the new lipid basis set provides a robust fitting strategy that improves 2HG evaluation in brain tumors with elevated lipids.

Multidimensional electronic spectroscopy in high-definition-Combining spectral, temporal, and spatial resolutions.

Over the past two decades, coherent multidimensional spectroscopies have been implemented across the terahertz, infrared, visible, and ultraviolet regions of the electromagnetic spectrum. A combination of coherent excitation of several resonances with few-cycle pulses, and spectral decongestion along multiple spectral dimensions, has enabled new insights into wide ranging molecular scale phenomena, such as energy and charge delocalization in natural and artificial light-harvesting systems, hydrogen bonding dynamics in monolayers, and strong light-matter couplings in Fabry-Pérot cavities. However, measurements on ensembles have implied signal averaging over relevant details, such as morphological and energetic inhomogeneity, which are not rephased by the Fourier transform. Recent extension of these spectroscopies to provide diffraction-limited spatial resolution, while maintaining temporal and spectral information, has been exciting and has paved a way to address several challenging questions by going beyond ensemble averaging. The aim of this Perspective is to discuss the technological developments that have eventually enabled spatially resolved multidimensional electronic spectroscopies and highlight some of the very recent findings already made possible by introducing spatial resolution in a powerful spectroscopic tool.

Effective normal modes identify vibrational motions which maximally promote vibronic mixing in excitonically coupled aggregates.

Controlling energy transfer through vibronic resonance is an interesting possibility. Exact treatment of non-adiabatic vibronic coupling is necessary to fully capture its role in driving energy transfer. However, the exact treatment of vibrations in extended systems is expensive, sometimes requiring oversimplifying approximations to reduce vibrational dimensionality, and do not provide physical insights into which specific vibrational motions promote energy transfer. In this communication, we derive effective normal modes for understanding vibronically enhanced energy transfer in excitonically coupled aggregates. We show that the dynamics of the overall high-dimensional vibronic Hamiltonian can be better understood through one-dimensional Hamiltonians separable along these effective modes. We demonstrate this approach on a trimer toy model to analyze the role of an intermediate "trap" site in mediating energy transfer between electronically uncoupled sites. Bringing uncoupled sites into vibronic resonance converts the "trap" into a "shuttle" for energy transfer. By deconvolving the dynamics along the aggregate normal modes, our approach identifies the specific vibrational motions, which maximally promote energy transfer, against spectator modes, which do not participate in vibronic mixing.

In vivo MRS measurement of 2-hydroxyglutarate in patient-derived IDH-mutant xenograft mouse models versus glioma patients.

PURPOSE: To generate a preclinical model of isocitrate dehydrogenase (IDH) mutant gliomas from glioma patients and design a MRS method to test the compatibility of 2-hydroxyglutarate (2HG) production between the preclinical model and patients. METHODS: Five patient-derived xenograft (PDX) mice were generated from two glioma patients with IDH1 R132H mutation. A PRESS sequence was tailored at 9.4 T, with computer simulation and phantom analyses, for improving 2HG detection in mice. 2HG and other metabolites in the PDX mice were measured using the optimized MRS at 9.4 T and compared with 3 T MRS measurements of the metabolites in the parental-tumor patients. Spectral fitting was performed with LCModel using in-house basis spectra. Metabolite levels were quantified with reference to water. RESULTS: The PRESS TE was optimized to be 96 ms, at which the 2HG 2.25 ppm signal was narrow and inverted, thereby leading to unequivocal separation of the 2HG resonance from adjacent signals from other metabolites. The optimized MRS provided precise detection of 2HG in mice compared to short-TE MRS at 9.4 T. The 2HG estimates in PDX mice were in excellent agreement with the 2HG measurements in the patients. CONCLUSION: The similarity of 2HG production between PDX models and parental-tumor patients indicates that PDX tumors retain the parental IDH metabolic fingerprint and can serve as a preclinical model for improving our understanding of the IDH-mutation associated metabolic reprogramming.

Vibronic resonance is inadequately described by one-particle basis sets.

Vibrational-electronic (vibronic) resonance and its possible role in energy and charge transfer have been experimentally and theoretically investigated in several photosynthetic proteins. Using a dimer modeled on a typical photosynthetic protein, we contrast the description of such excitons provided by an exact basis set description, as opposed to a basis set with reduced vibrational dimensionality. Using a reduced analytical description of the full Hamiltonian, we show that in the presence of vibrational excitation both on electronically excited as well as unexcited sites, constructive interference between such basis states causes vibronic coupling between excitons to become progressively stronger with increasing quanta of vibrational excitation. This effect leads to three distinguishing features of excitons coupled through a vibronic resonance, which are not captured in basis sets that restrict ground state vibrations: (1) the vibronic resonance criterion itself, (2) vibronically assisted perfect delocalization between sites even though purely electronic mixing between the sites is imperfect due to energetic disorder, and (3) the nuclear distortion accompanying vibronic excitons becoming increasingly larger for resonant vibronic coupling involving higher vibrational quanta. In terms of spectroscopically observable limitations of reduced basis set descriptions of vibronic resonance, several differences are seen in absorption and emission spectra but may be obscured on account of overwhelming line broadening. However, we show that several features such as vibronic exciton delocalization and vibrational distortions associated with electronic excitations, which ultimately dictate the excited state wavepacket motions and relaxation processes, are fundamentally not described by basis sets that restrict ground state vibrations.

A cadaveric morphometric analysis of coracoid process with reference to the Latarjet procedure using the "congruent arc technique".

INTRODUCTION: Congruent arc Latarjet procedure involves rotating the coracoid process so that its inferior surface is flush with the glenoid face, owing to their matching radius of curvature (ROC). However, there has been no cadaveric study to actually measure and compare the ROC of coracoid with glenoid, especially in Indian population. MATERIALS AND METHODS: 44 shoulders were dissected in 24 cadavers to measure usable length of coracoid process, width, height, ROC of coracoid and glenoid as well as ulnar length (as proxy of cadaver height). Critical coracoid height and length were estimated based on screw sizes of 2.7 mm, 3.5 mm, 4 mm and 4.5 mm, and pair concordance between height and length calculated. ROC of coracoid and glenoid were compared to measure extent of congruency. RESULTS: The mean usable length of coracoid process, width and height at mid-point were 21.8 mm, 13.7 mm and 8.6 mm, respectively. Out of the different screw sizes, 2.7 mm screws were found safe in 82% shoulders. 24 coracoid-glenoid pairs fulfilled the operational definition (≤ 5 mm) of congruency while rest 20 were seemingly incongruent chiefly due to coracoid variations, with mean ROC difference 4.13 mm (95% CI 1.51-6.74 mm). The ulnar length was significantly smaller in the incongruent ROC group (p = 0.0002). CONCLUSIONS: The available length as well as height of the transferred coracoid must be considered when deciding optimum diameter fixation screws in Latarjet procedure. Owing to smaller anatomic dimensions of coracoid in Indian population, 2.7-mm screws provide the safest fixation option. Also, the ROC of coracoid and glenoid does not match in substantial proportion of the cadavers. Pre-operative planning should include a CT-based assessment of glenoid and coracoid dimensions to decide the technique of Latarjet procedure and the optimum diameter fixation screws required.

3D high-resolution imaging of 2-hydroxyglutarate in glioma patients using DRAG-EPSI at 3T in vivo.

PURPOSE: To develop 3D high-resolution imaging of 2-hydroxyglutarate (2HG) at 3T in vivo. METHODS: Echo-planar spectroscopic imaging with dual-readout alternated-gradients (DRAG-EPSI), which was recently reported for 2D imaging of 2HG at 7T, was tested for 3D imaging of 2HG at 3T. The frequency drifts and acoustic noise induced by DRAG-EPSI were investigated in comparison with conventional EPSI. Four patients with IDH-mutant gliomas were enrolled for 3D imaging of 2HG and other metabolites. A previously reported 2HG-tailored TE 97-ms PRESS sequence preceded the DRAG-EPSI readout gradients. Unsuppressed water, acquired with EPSI, was used as reference for multi-channel combination, eddy-current compensation, and metabolite quantification. Spectral fitting was conducted with the LCModel using in-house basis sets. RESULTS: With gradient strength of 4 mT/m and slew rate of 20 mT/m/ms, DRAG-EPSI produced frequency drifts smaller by 5.5-fold and acoustic noise lower by 25 dB compared to conventional EPSI. In a 19-min scan, 3D DRAG-EPSI provided images of 2HG with precision (CRLB <10%) at a resolution of 10 × 10 × 10 mm3 for a field of view of 240 × 180 × 80 mm3 . 2HG was estimated to be 5 mM in a pre-treatment patient. In 3 post-surgery patients, 2HG estimates were 3-6 mM, and the 2HG distribution was different from the water-T2 image pattern or highly concentrated in the post-contrast enhancing region. CONCLUSION: Together with 2HG-optimized PRESS, DRAG-EPSI provides an effective tool for reliable 3D high-resolution imaging of 2HG at 3T in vivo.

New mobile-bearing TKA with unique ball and socket post-cam mechanism offers similar function and stability with better prosthesis fit and gap balancing compared to an established fixed-bearing prosthesis.

PURPOSE: A mobile-bearing (MB) posterior-stabilized total knee arthroplasty (TKA) system with ball and socket post-cam mechanism has been developed with the aims of better prosthesis fit and enhanced stability. However, the data are limited to compare its clinical outcomes with an already established fixed-bearing (FB) implant design. METHODS: This is a prospective randomized study comparing 260 patients in the MB group and 133 patients in FB group with a minimum 2 years of follow-up. Intraoperative variables, post-operative functional outcomes and incidence of adverse events were compared. RESULTS: MB group showed better prosthesis fit as the incidence of over-hang of femoral component at junction (medial: 1% vs. 5% and lateral: 2% vs 4%, p < 0.001) and trochlea (medial: 2% vs 30%, p = 0.042 and lateral: 13% vs 21%, p = 0.015) was less than FB group. MB group also showed better gap balancing as the incidence of medio-lateral gap difference more than 2 mm was less in flexion (2.3% vs. 16%, p < 0.001) and extension (3.1% vs. 9.8%, p = 0.005). Post-operative functional outcomes and incidence of adverse events showed no difference between the two groups at 2 years. CONCLUSIONS: New MB design offers similar functional outcomes and stability along with better intraoperative prosthesis fit and gap balancing compared to an established fixed-bearing design. Hence, this new MB design could be an alternative prosthesis of choice for posterior-stabilized TKA. LEVEL OF EVIDENCE: I.

Clinical and radiological analysis of a personalized total knee arthroplasty system design.

PURPOSE: The objectives of this study were to determine the radiological outcome of a new personalized total knee arthroplasty (TKA) design and also to analyze the radiological reproducibility of the surgical technique. PATIENTS AND METHODS: A total of 100 consecutive TKAs performed in 99 patients using Persona knee system were recruited. Weight-bearing standing anteroposterior and lateral radiographs were done in all the patients, both pre-operatively as well as post-operatively, and various radiological parameters were analyzed and compared. RESULTS: The full correction of the limb mechanical axis was achieved in 97% of patients, and the radiological parameters of coronal and sagittal alignment of femoral and tibial components showed good results. There were no substantial differences between the mean pre-operative and post-operative patellar height indices, and data were in the normal range. Posterior condylar offset (PCO) and posterior condylar offset ratio (PCOR) had increased as expected after TKA. The coverage of tibia was optimal with data in the normal range. CONCLUSIONS: Radiological assessment of the new personalized knee system design showed excellent results with various parameters restored to the normal values. Therefore, the prosthesis can be considered anatomic, and the surgical technique is reproducible allowing the prosthesis to be implanted easily and with high precision.

Temporal patterns of commonly used clinical outcome scales during a 5-year period after total knee arthroplasty.

BACKGROUND: It is not established beyond doubt whether improvements in functional outcome after total knee arthroplasty (TKA) are maintained in the long term. We therefore investigated the temporal patterns of functional outcome [using range of motion (ROM), American Knee Society (AKS) score, Western Ontario and McMaster Universities Arthritis Index (WOMAC) score, and 36-Item Short Form Health Survey (SF-36) score] over a 5-year period after uncomplicated TKA, and whether these patterns differed by implant type and patient age. MATERIALS AND METHODS: This prospective study evaluated 138 patients who underwent unilateral TKA with either a mobile-bearing (MB) or fixed-bearing (FB) posterior-stabilized prosthesis. An independent investigator evaluated the functional outcome at five time points: preoperatively and at 6-month, 1-year, 2-year, and 5-year follow-up. Differences in functional outcomes between adjacent time points were evaluated by mixed-effect model repeat measurement (MMRM). RESULTS: The different functional outcome scores showed improvement till 6 months-2 years, followed by a variable decline. In patients aged ≥ 68 years with an MB implant, most of the functional outcome scores declined between 2 and 5 years after variable initial improvement till 6 months-2 years, whereas the parameters plateaued after 2 years in those aged < 68 years and in older patients with an FB implant. CONCLUSIONS: A decline in function and pain relief occurs 2 years after TKA. This decline is more evident in older patients with an MB prosthesis. Based on these findings, we believe that use of MB implants in older patients (≥ 68 years) requires further investigation. LEVEL OF EVIDENCE: Level 3.

Distinction of the GABA 2.29 ppm resonance using triple refocusing at 3 T in vivo.

PURPOSE: To develop 1 H MR spectroscopy that provides distinction of γ-aminobutyric acid (GABA) signal at 3 T in vivo. METHODS: Triple-refocusing was tailored at 3 T, with numerical simulations and phantom validation, for distinction of the GABA 2.29-ppm resonance from the neighboring glutamate resonance. The optimization was performed on the inter-RF pulse time delays and the duration and carrier frequency of a non-slice-selective RF pulse. The optimized triple refocusing was tested in multiple regions in 6 healthy subjects, including hippocampus. The in vivo spectra were analyzed with the LCModel using in-house basis spectra. After normalization of the metabolite signal estimates to water, the metabolite concentrations were quantified with reference to medial-occipital creatine at 8 mM. RESULTS: A triple-refocusing scheme with optimized inter-RF pulse time delays (TE = 74 ms) was obtained for GABA detection. With optimized duration (14 ms) and carrier frequency (4.5 ppm) of the non-slice-selective RF pulse, the triple refocusing gave rise to distinction between the GABA 2.29-ppm and glutamate 2.35-ppm signals. The GABA 2.29-ppm signal was clearly discernible in spectra in vivo (voxel size 4 to 12 mL; scan times 4.3 to 17 minutes). With a total of 24 spectra from 6 gray or white matter-dominant regions, the GABA concentration was measured to be 0.62 to 1.15 mM (Cramer-Rao lower bound of 8 to 14%), and the glutamate level 5.8 to 11.2 mM (Cramer-Rao lower bound of 3 to 6%). CONCLUSION: The optimized triple refocusing provided distinction between GABA and glutamate signals and permitted direct codetection of these metabolites in the human brain at 3 T in vivo.

Echo-planar spectroscopic imaging with dual-readout alternated gradients (DRAG-EPSI) at 7 T: Application for 2-hydroxyglutarate imaging in glioma patients.

PURPOSE: To develop echo-planar spectroscopic imaging (EPSI) with large spectral width and accomplish high-resolution imaging of 2-hydroxyglutarate (2HG) at 7 T. METHODS: We designed a new EPSI readout scheme at 7 T. Data were recorded with dual-readout alternated gradients and combined according to the gradient polarity. Following validation of its performance in phantoms, the new readout scheme, together with previously reported 2HG-optimized magnetic resonance spectroscopy (point-resolved spectroscopy echo time of 78 ms), was used for time-efficient and high-resolution imaging of 2HG and other metabolites in five glioma patients before treatment. Unsuppressed water, acquired with EPSI, was used as reference for multichannel combination, eddy-current compensation, and metabolite quantification. Spectral fitting was conducted with the LCModel using in-house calculated basis sets. RESULTS: Using a readout gradient strength of 9.5 mT/m and slew rate of 90 mT/m/ms, dual-readout alternated gradients EPSI permitted 1638-Hz spectral width with 6 × 6 mm2 in-plane resolution at 7 T. Phantom data indicated that dual-readout alternated gradients EPSI provides proper metabolite signals and induces much less frequency drifts than conventional EPSI. For a spatial resolution of 0.5 mL, 2HG was detected in tumors with precision (Cramer-Rao lower bound < 10%). The 2HG was estimated to be 2.3 to 3.3 mM in tumors of three patients with biopsy-proven isocitrate dehydrogenase (IDH) mutant gliomas. The 2HG was undetectable in an IDH wild-type glioblastoma. For a radiographically suggested glioma, the estimated 2HG of 2.3 ± 0.2 mM (Cramer-Rao lower bound < 10%) indicated that the lesion may be an IDH mutant glioma. CONCLUSIONS: The data indicated that the dual-readout alternated gradients EPSI can provide reliable high-resolution imaging of 2HG in glioma patients at 7 T in vivo. Magn Reson Med 79:1851-1861, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Strongly coupled bacteriochlorin dyad studied using phase-modulated fluorescence-detected two-dimensional electronic spectroscopy.

Fluorescence-detected two-dimensional electronic spectroscopy (F-2DES) projects the third-order non-linear polarization in a system as an excited electronic state population which is incoherently detected as fluorescence. Multiple variants of F-2DES have been developed. Here, we report phase-modulated F-2DES measurements on a strongly coupled symmetric bacteriochlorin dyad, a relevant 'toy' model for photosynthetic energy and charge transfer. Coherence map analysis shows that the strongest frequency observed in the dyad is well-separated from the excited state electronic energy gap, and is consistent with a vibrational frequency readily observed in bacteriochlorin monomers. Kinetic rate maps show a picosecond relaxation timescale between the excited states of the dyad. To our knowledge this is the first demonstration of coherence and kinetic analysis using the phase-modulation approach to F-2DES.

Electronic energy transfer through non-adiabatic vibrational-electronic resonance. II. 1D spectra for a dimer.

Vibrational-electronic resonance in photosynthetic pigment-protein complexes invalidates Förster's adiabatic framework for interpreting spectra and energy transfer, thus complicating determination of how the surrounding protein affects pigment properties. This paper considers the combined effects of vibrational-electronic resonance and inhomogeneous variations in the electronic excitation energies of pigments at different sites on absorption, emission, circular dichroism, and hole-burning spectra for a non-degenerate homodimer. The non-degenerate homodimer has identical pigments in different sites that generate differences in electronic energies, with parameters loosely based on bacteriochlorophyll a pigments in the Fenna-Matthews-Olson antenna protein. To explain the intensity borrowing, the excited state vibrational-electronic eigenvectors are discussed in terms of the vibrational basis localized on the individual pigments, as well as the correlated/anti-correlated vibrational basis delocalized over both pigments. Compared to those in the isolated pigment, vibrational satellites for the correlated vibration have the same frequency and precisely a factor of 2 intensity reduction through vibrational delocalization in both absorption and emission. Vibrational satellites for anti-correlated vibrations have their relaxed emission intensity reduced by over a factor 2 through vibrational and excitonic delocalization. In absorption, anti-correlated vibrational satellites borrow excitonic intensity but can be broadened away by the combination of vibronic resonance and site inhomogeneity; in parallel, their vibronically resonant excitonic partners are also broadened away. These considerations are consistent with photosynthetic antenna hole-burning spectra, where sharp vibrational and excitonic satellites are absent. Vibrational-excitonic resonance barely alters the inhomogeneously broadened linear absorption, emission, and circular dichroism spectra from those for a purely electronic excitonic coupling model. Energy transfer can leave excess energy behind as vibration on the electronic ground state of the donor, allowing vibrational relaxation on the donor's ground electronic state to make energy transfer permanent by removing excess energy from the excited electronic state of the dimer.

Detection of 2-hydroxyglutarate in brain tumors by triple-refocusing MR spectroscopy at 3T in vivo.

PURPOSE: To test the efficacy of triple-refocusing MR spectroscopy (MRS) for improved detection of 2-hydroxyglutarate (2HG) in brain tumors at 3T in vivo. METHODS: The triple-refocusing sequence parameters were tailored at 3T, with density-matrix simulations and phantom validation, for enhancing the 2HG 2.25-ppm signal selectivity with respect to the adjacent resonances of glutamate (Glu), glutamine (Gln), and gamma-aminobutyric acid (GABA). In vivo MRS data were acquired from 15 glioma patients and analyzed with LCModel using calculated basis spectra. Metabolites were quantified with reference to water. RESULTS: A triple-refocusing sequence (echo time = 137 ms) was obtained for 2HG detection. The 2HG 2.25-ppm signal was large and narrow while the Glu and Gln signals between 2.2 and 2.3 ppm were minimal. The optimized triple refocusing offered improved separation of 2HG from Glu, Gln and GABA when compared with published MRS methods. 2HG was detected in all 15 patients, the estimated 2HG concentrations ranging from 2.4 to 15.0 mM, with Cramer-Rao lower bounds of 2%-11%. The 2HG estimates did not show significant correlation with total choline. CONCLUSION: The optimized triple refocusing provides excellent 2HG signal discrimination from adjacent resonances and may confer reliable in vivo measurement of 2HG at relatively low concentrations. Magn Reson Med 78:40-48, 2017. © 2016 International Society for Magnetic Resonance in Medicine.