Chemical Analysis of an Isotopically Labeled Molecule Using Two-Dimensional NMR Spectroscopy at 34 µT.

Low-field nuclear magnetic resonance (NMR) spectroscopy, conducted at or below a few millitesla, provides only limited spectral information due to its inability to resolve chemical shifts. Thus, chemical analysis based on this technique remains challenging. One potential solution to overcome this limitation is the use of isotopically labeled molecules. However, such compounds, particularly their use in two-dimensional (2D) NMR techniques, have rarely been studied. This study presents the results of both experimental and simulated correlation spectroscopy (COSY) on 1-13C-ethanol at 34.38 µT. The strong heteronuclear coupling in this molecule breaks the magnetic equivalence, causing all J-couplings, including homonuclear coupling, to split the 1H spectrum. The obtained COSY spectrum clearly shows the spectral details. Furthermore, we observed that homonuclear coupling between 1H spins generated cross-peaks only when the associated 1H spins were coupled to identical 13C spin states. Our findings demonstrate that a low-field 2D spectrum, even with a moderate spectral line width, can reveal the J-coupling networks of isotopically labeled molecules.

Dual-Emissive Mn-Doped Lead Halide Perovskite Nanocrystals as Background-Suppressed Latent Fingerprint Detection Probes.

Diverse strategies have been developed to visualize latent fingerprints (LFPs) that are undetectable by the naked eye. Among them, fluorescence-based approaches have emerged as an attractive method for enabling high-resolution LFP imaging. However, the use of fluorescent probes for LFP detection remains challenging due to cumbersome processing, low selectivity, and high background interference. Here, we demonstrate highly efficient, sensitive, and background-free LFP detection with dual-color emission arising from manganese (Mn)-doped lead halide perovskite (CsPb(Cl1-yBry)3) nanocrystals (NCs). The resulting bright, fluorescent, solid-state nanopowder (NP) permits the visualization of LFP ridge structures and the resolution of level 1-3 LFP features. The dual-color emission of the Mn-doped perovskite NP provides a simple, robust, and effective route to overcome background interference, thereby increasing the resolution and sensitivity of the LFP detection. The combination of the high quantum efficiency and dual emission of Mn-doped perovskite NP offers great potential for forensic science.

Frequency Limits of Sequential Readout for Sensing AC Magnetic Fields Using Nitrogen-Vacancy Centers in Diamond.

The nitrogen-vacancy (NV) centers in diamond have the ability to sense alternating-current (AC) magnetic fields with high spatial resolution. However, the frequency range of AC sensing protocols based on dynamical decoupling (DD) sequences has not been thoroughly explored experimentally. In this work, we aimed to determine the sensitivity of the ac magnetic field as a function of frequency using the sequential readout method. The upper limit at high frequency is clearly determined by Rabi frequency, in line with the expected effect of finite DD-pulse width. In contrast, the lower frequency limit is primarily governed by the duration of optical repolarization rather than the decoherence time (T2) of NV spins. This becomes particularly crucial when the repetition (dwell) time of the sequential readout is fixed to maintain the acquisition bandwidth. The equation we provide successfully describes the tendency in the frequency dependence. In addition, at the near-optimal frequency of 1 MHz, we reached a maximum sensitivity of 229 pT/Hz by employing the XY4-(4) DD sequence.

Background free in vivo29Si MR imaging with hyperpolarized PEGylated silicon nanoparticles.

This study demonstrated the potential of 50 nm PEGylated Si NPs for high-resolution in vivo29Si MR imaging, emphasizing their biocompatibility and water dispersibility. The acquisition of in vivo Si MR images using the lowest reported dose after subcutaneous and intraperitoneal administration opens new avenues for future 29Si MR studies.

Mesoporous Polydopamine-Encapsulated Fluorescent Nanodiamonds: A Versatile Platform for Biomedical Applications.

Fluorescent nanodiamonds (FNDs) are versatile nanomaterials with promising properties. However, efficient functionalization of FNDs for biomedical applications remains challenging. In this study, we demonstrate mesoporous polydopamine (mPDA) encapsulation of FNDs. The mPDA shell is generated by sequential formation of micelles via self-assembly of Pluronic F127 (F127) with 1,3,5-trimethyl benzene (TMB) and composite micelles via oxidation and self-polymerization of dopamine hydrochloride (DA). The surface of the mPDA shell can be readily functionalized with thiol-terminated methoxy polyethylene glycol (mPEG-SH), hyperbranched polyglycerol (HPG), and d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS). The PEGylated FND@mPDA particles are efficiently taken up by, and employed as a fluorescent imaging probe for, HeLa cells. HPG-functionalized FND@mPDA is conjugated with an amino-terminated oligonucleotide to detect microRNA via hybridization. Finally, the increased surface area of the mPDA shell permits efficient loading of doxorubicin hydrochloride. Further modification with TPGS increases drug delivery efficiency, resulting in high toxicity to cancer cells.

Dynamic Nuclear Polarization of Selectively 29Si-Enriched Core@shell Silica Nanoparticles.

29Si silica nanoparticles (SiO2 NPs) are promising magnetic resonance imaging (MRI) probes that possess advantageous properties for in vivo applications, including suitable biocompatibility, tailorable properties, and high water dispersibility. Dynamic nuclear polarization (DNP) is used to enhance 29Si MR signals via enhanced nuclear spin alignment; to date, there has been limited success employing DNP for SiO2 NPs due to the lack of endogenous electronic defects that are required for the process. To create opportunities for SiO2-based 29Si MRI probes, we synthesized variously featured SiO2 NPs with selective 29Si isotope enrichment on homogeneous and core@shell structures (shell thickness: 10 nm, core size: 40 nm), and identified the critical factors for optimal DNP signal enhancement as well as the effective hyperpolarization depth when using an exogenous radical. Based on the synthetic design, this critical factor is the proportion of 29Si in the shell layer regardless of core enrichment. Furthermore, the effective depth of hyperpolarization is less than 10 nm between the surface and core, which demonstrates an approximately 40% elongated diffusion length for the shell-enriched NPs compared to the natural abundance NPs. This improved regulation of surface properties facilitates the development of isotopically enriched SiO2 NPs as hyperpolarized contrast agents for in vivo MRI.

Hyperpolarized 29Si magnetic resonance spectroscopy of selectively radical-embedded silica nanoparticles.

The embedding of radicals at different locations within core@shell silica nanoparticles contributes to enhanced polarization capability and can be self-polarized without adding external radicals. With grafting the radical source homogenously inside of the nanoparticles, a significant 29Si hyperpolarization signal enhancement of 49.4 was obtained.

Detection of the 40 Hz auditory steady-state response with optically pumped magnetometers.

Magnetoencephalography (MEG) is a functional neuroimaging technique that noninvasively detects the brain magnetic field from neuronal activations. Conventional MEG measures brain signals using superconducting quantum interference devices (SQUIDs). SQUID-MEG requires a cryogenic environment involving a bulky non-magnetic Dewar flask and the consumption of liquid helium, which restricts the variability of the sensor array and the gap between the cortical sources and sensors. Recently, miniature optically pumped magnetometers (OPMs) have been developed and commercialized. OPMs do not require cryogenic cooling and can be placed within millimeters from the scalp. In the present study, we arranged six OPM sensors on the temporal area to detect auditory-related brain responses in a two-layer magnetically shielded room. We presented the auditory stimuli of 1 kHz pure-tone bursts with 200 ms duration and obtained the M50 and M100 components of auditory-evoked fields. We delivered the periodic stimuli with a 40 Hz repetition rate and observed the gamma-band power changes and inter-trial phase coherence of auditory steady-state responses at 40 Hz. We found that the OPM sensors have a performance comparable to that of conventional SQUID-MEG sensors, and our results suggest the feasibility of using OPM sensors for functional neuroimaging and brain-computer interface applications.

Optical Dynamic Nuclear Polarization of 13C Spins in Diamond at a Low Field with Multi-Tone Microwave Irradiation.

Majority of dynamic nuclear polarization (DNP) experiments have been requiring helium cryogenics and strong magnetic fields for a high degree of nuclear polarization. In this work, we instead demonstrate an optical hyperpolarization of naturally abundant 13C nuclei in a diamond crystal at a low magnetic field and the room temperature. It exploits continuous laser irradiation for polarizing electronic spins of nitrogen vacancy centers and microwave irradiation for transferring the electronic polarization to 13C nuclear spins. We have studied the dependence of 13C polarization on laser and microwave powers. For the first time, a triplet structure corresponding to the 14N hyperfine splitting has been observed in the 13C polarization spectrum. By simultaneously exciting three microwave frequencies at the peaks of the triplet, we have achieved 13C bulk polarization of 0.113 %, leading to an enhancement of 90,000 over the thermal polarization at 17.6 mT. We believe that the multi-tone irradiation can be extended to further enhance the 13C polarization at a low magnetic field.

29Si Isotope-Enriched Silicon Nanoparticles for an Efficient Hyperpolarized Magnetic Resonance Imaging Probe.

Silicon particles have garnered attention as promising biomedical probes for hyperpolarized 29Si magnetic resonance imaging and spectroscopy. However, due to the limited levels of hyperpolarization for nanosized silicon particles, microscale silicon particles have primarily been the focus of dynamic nuclear polarization (DNP) applications, including in vivo magnetic resonance imaging (MRI). To address these current challenges, we developed a facile synthetic method for partially 29Si-enriched porous silicon nanoparticles (NPs) (160 nm) and examined their usability in hyperpolarized 29Si MRI agents with enhanced signals in spectroscopy and imaging. Hyperpolarization characteristics, such as the build-up constant, the depolarization time (T1), and the overall enhancement of the 29Si-enriched silicon NPs (10 and 15%), were thoroughly investigated and compared with those of a naturally abundant NP (4.7%). During optimal DNP conditions, the 15% enriched silicon NPs showed more than 16-fold higher enhancements─far beyond the enrichment ratio─than the naturally abundant sample, further improving the signal-to-noise ratio in in vivo 29Si MRI. The 29Si-enriched porous silicon NPs used in this work are potentially capable to serve as drug-delivery vehicles in addition to hyperpolarized 29Si in vivo, further enabling their potential future applicability as a theragnostic platform.

SQUID-based ultralow-field MRI of a hyperpolarized material using signal amplification by reversible exchange.

The signal amplification by reversible exchange (SABRE) technique is a very promising method for increasing magnetic resonance (MR) signals. SABRE can play a particularly large role in studies with a low or ultralow magnetic field because they suffer from a low signal-to-noise ratio. In this work, we conducted real-time superconducting quantum interference device (SQUID)-based nuclear magnetic resonance (NMR)/magnetic resonance imaging (MRI) studies in a microtesla-range magnetic field using the SABRE technique after designing a bubble-separated phantom. A maximum enhancement of 2658 for 1H was obtained for pyridine in the SABRE-NMR experiment. A clear SABRE-enhanced MR image of the bubble-separated phantom, in which the para-hydrogen gas was bubbling at only the margin, was successfully obtained at 34.3 µT. The results show that SABRE can be successfully incorporated into an ultralow-field MRI system, which enables new SQUID-based MRI applications. SABRE can shorten the MRI operation time by more than 6 orders of magnitude and establish a firm basis for future low-field MRI applications.

Dynamic nuclear polarisation of liquids at one microtesla using circularly polarised RF with application to millimetre resolution MRI.

Magnetic resonance imaging in ultra-low fields is often limited by mediocre signal-to-noise ratio hindering a higher resolution. Overhauser dynamic nuclear polarisation (O-DNP) using nitroxide radicals has been an efficient solution for enhancing the thermal nuclear polarisation. However, the concurrence of positive and negative polarisation enhancements arises in ultra-low fields resulting in a significantly reduced net enhancement, making O-DNP far less attractive. Here, we address this issue by applying circularly polarised RF. O-DNP with circularly polarised RF renders a considerably improved enhancement factor of around 150,000 at 1.2 µT. A birdcage coil was adopted into an ultra-low field MRI system to generate the circularly polarised RF field homogeneously over a large volume. We acquired an MR image of a nitroxide radical solution with an average in-plane resolution of 1 mm. De-noising through compressive sensing further improved the image quality.

In-situ Overhauser-enhanced nuclear magnetic resonance at less than 1 µT using an atomic magnetometer.

The development of atomic magnetometers has led to nuclear magnetic resonance (NMR) in zero and ultralow magnetic fields without using cryogenic sensors. However, in-situ detection, meaning that a sample locates in the detection space beside a vapor cell, has been conducted only with parahydrogen-induced polarization. Other hyperpolarization techniques remain unexplored yet. In this work, we demonstrate that Overhauser dynamic nuclear polarization allows in-situ NMR detection with an atomic magnetometer at less than 1 µT. The 1H NMR signal of a nitroxide radical solution was observed at 13.83 Hz, which corresponds to 325 nT. Signal-to-noise ratio was 32 after sixteen averages. On the Larmor precession of 1H spins, a decaying oscillation was superimposed. We attribute it to a transient 87Rb spin precession in response to a non-adiabatic field variation. This work shows a new capability of zero- and ultralow-field NMR.

3'-UTR Polymorphisms of MTHFR and TS Associated with Osteoporotic Vertebral Compression Fracture Susceptibility in Postmenopausal Women.

Postmenopausal osteoporosis is one of the most prominent diseases in postmenopausal women and it is increasing in prevalence with the aging population. Furthermore, osteoporosis and osteoporotic vertebral compression fractures (OVCFs) are related to mortality and decreased quality of life. Therefore, searching for biomarkers that are able to identify postmenopausal women who are at high risk of developing OVCFs is an effective strategy for improving the quality of life of patients and alleviating social and economic burdens. In this study, we investigated methylenetetrahydrofolate reductase (MTHFR) and thymidylate synthase (TS) gene polymorphisms in postmenopausal women with OVCF. We recruited 301 postmenopausal women and performed genotyping for the presence of MTHFR 2572C>A, 4869C>G and TS 1100C>T, 1170A>G. Genotyping was analyzed using the polymerization chain reaction restriction fragment length polymorphism assay. MTHFR 2572C>A and TS 1100C>T were associated with the prevalence of osteoporosis (MTHFR 2572CC versus CA+AA: odd ratio [OR] adjusted age, hypertention [HTN], and diabetes mellitus [DM] = 0.49, p = 0.012) and the occurrence of OVCFs (MTHFR 2572CC versus CA+AA: OR adjusted age, HTN, and DM = 0.38, p = 0.013; TS 1100CC versus CT+TT: OR adjusted age, HTN, and DM = 0.46, p = 0.02). Our novel finding is the identification of MTHFR and TS genetic variants that decrease susceptibility to OVCFs. Our findings suggest that polymorphisms in the MTHFR and TS genes are associated with susceptibility to osteoporosis and OVCFs in postmenopausal women.

Complete Reversal of Diffusion Restriction after Treatment of Traumatic Carotid-Cavernous Fistula.

A 15-year-old man presented with stupor following a motorcycle traffic accident. The patient was diagnosed with a traumatic left carotid cavernous fistula (CCF) with pseudoaneurysm of the left internal carotid artery. Brain magnetic resonance imaging (MRI) showed transiently restricted diffusion in the left centrum semiovale white matter and lower temporo-occipital area extending to the splenium of the corpus callosum, with high signal intensity on diffusion-weighted imaging. On the 35th day of admission, the patient had complete neurological recovery and a follow-up brain MRI revealed complete resolution of the lesions in the left centrum semiovale and splenium of the corpus callosum. These clinical and radiological features are highly suggestive of complete reversal of diffusion restriction after successful embolization of traumatic CCF.

Safety and tolerability of intradiscal implantation of combined autologous adipose-derived mesenchymal stem cells and hyaluronic acid in patients with chronic discogenic low back pain: 1-year follow-up of a phase I study.

BACKGROUND: Adipose tissue-derived mesenchymal stem cells (AT-MSCs) offer potential as a therapeutic option for chronic discogenic low back pain (LBP) because of their immunomodulatory functions and capacity for cartilage differentiation. The goal of this study was to assess the safety and tolerability of a single intradiscal implantation of combined AT-MSCs and hyaluronic acid (HA) derivative in patients with chronic discogenic LBP. METHODS: We performed a single-arm phase I clinical trial with a 12-month follow-up and enrolled 10 eligible chronic LBP patients. Chronic LBP had lasted for more than 3 months with a minimum intensity of 4/10 on a visual analogue scale (VAS) and disability level ≥ 30% on the Oswestry Disability Index (ODI). The 10 patients underwent a single intradiscal injection of combined HA derivative and AT-MSCs at a dose of 2 × 107 cells/disc (n = 5) or 4 × 107 cells/disc (n = 5). Safety and treatment outcomes were evaluated by assessing VAS, ODI, Short Form-36 (SF-36), and imaging (lumbar spine X-ray imaging and MRI) at regular intervals over 1 year. RESULTS: No patients were lost at any point during the 1-year clinical study. We observed no procedure or stem cell-related adverse events or serious adverse events during the 1-year follow-up period. VAS, ODI, and SF-36 scores significantly improved in both groups receiving both low (cases 2, 4, and 5) and high (cases 7, 8, and 9) cell doses, and did not differ significantly between the two groups. Among six patients who achieved significant improvement in VAS, ODI, and SF-36, three patients (cases 4, 8, and 9) were determined to have increased water content based on an increased apparent diffusion coefficient on diffusion MRI. CONCLUSIONS: Combined implantation of AT-MSCs and HA derivative in chronic discogenic LBP is safe and tolerable. However, the efficacy of combined AT-MSCs and HA should be investigated in a randomized controlled trial in a larger population. TRIAL REGISTRATION: ClinicalTrials.gov NCT02338271 . Registered 7 January 2015.

Orbital reorientation in MnV2O4 observed by V NMR.

The simultaneous occurrence of the structural and magnetic phase transitions observed in MnV2O4 is one clear example of strong interplay among the spin, orbital and lattice degrees of freedom. The structure of MnV2O4 is switched by the magnetic field and the linear magnetostriction is very high. The orbital order mediates the interaction between the spin and the lattice generating these phenomena. In this work, we present experimental evidence of an orbital order in MnV2O4 and its reorientation under a rotating magnetic field as obtained by nuclear magnetic resonance(NMR). The shift in the resonance frequency of the V NMR spectrum is symmetrical with respect to 45° as an external magnetic field of 7 T rotates from the c-axis to the b-axis, indicating that the initial easy axis flips to the orthogonal direction most parallel to the field direction. The spectrum of V3+ ions splits into four peaks with a maximum shift of 40 MHz. Our analysis revealed that this is the combined effect of the anisotropic hyperfine field due to an ordered orbital and the dipolar hyperfine field. Reorientation of the orbital order in response to an external magnetic field accompanies the macroscopically observed magnetostriction in MnV2O4.

Dynamic nuclear polarization in the hyperfine-field-dominant region.

Dynamic nuclear polarization (DNP) allows measuring enhanced nuclear magnetic resonance (NMR) signals. Though the efficiency of DNP has been known to increase at low fields, the usefulness of DNP has not been throughly investigated yet. Here, using a superconducting quantum interference device-based NMR system, we performed a series of DNP experiments with a nitroxide radical and measured DNP spectra at several magnetic fields down to sub-microtesla. In the DNP spectra, the large overlap of two peaks having opposite signs results in net enhancement factors, which are significantly lower than theoretical expectations and nearly invariant with respect to magnetic fields below the Earth's field. The numerical analysis based on the radical's Hamiltonian provides qualitative explanations of such features. The net enhancement factor reached 325 at maximum experimentally, but our analysis reveals that the local enhancement factor at the center of the rf coil is 575, which is unaffected by detection schemes. We conclude that DNP in the hyperfine-field-dominant region yields sufficiently enhanced NMR signals at magnetic fields above 1 µT.

T 1 relaxation measurement of ex-vivo breast cancer tissues at ultralow magnetic fields.

We investigated T 1 relaxations of ex-vivo cancer tissues at low magnetic fields in order to check the possibility of achieving a T 1 contrast higher than those obtained at high fields. The T 1 relaxations of fifteen pairs (normal and cancerous) of breast tissue samples were measured at three magnetic fields, 37, 62, and 122 µT, using our superconducting quantum interference device-based ultralow field nuclear magnetic resonance setup, optimally developed for ex-vivo tissue studies. A signal reconstruction based on Bayesian statistics for noise reduction was exploited to overcome the low signal-to-noise ratio. The ductal and lobular-type tissues did not exhibit meaningful T 1 contrast values between normal and cancerous tissues at the three different fields. On the other hand, an enhanced T 1 contrast was obtained for the mucinous cancer tissue.

Flat-response spin-exchange relaxation free atomic magnetometer under negative feedback.

We demonstrate that the use of negative feedback extends the detection bandwidth of an atomic magnetometer in a spin-exchange relaxation free (SERF) regime. A flat-frequency response from zero to 190 Hz was achieved, which is nearly a three-fold enhancement while maintaining sensitivity, 3 fT/Hz1/2 at 100 Hz. With the extension of the bandwidth, the linear correlation between measured signals and a magne-tocardiographic field synthesized for comparison was increased from 0.21 to 0.74. This result supports the feasibility of measuring weak biomagnetic signals containing multiple frequency components using a SERF atomic magnetometer under negative feedback.