Inductively coupled, transmit-receive coils for proton MRI and X-nucleus MRI/MRS in small animals.

We report several inductively coupled RF coil designs that are very easy to construct, produce high signal-to-noise ratio (SNR) and high spatial resolution while accommodating life support, anesthesia and monitoring in small animals. Inductively coupled surface coils were designed for hyperpolarized 13 C MR spectroscopic imaging (MRSI) of mouse brain, with emphases on the simplicity of the circuit design, ease of use, whole-brain coverage, and high SNR. The simplest form was a resonant loop designed to crown the mouse head for a snug fit to achieve full coverage of the brain with high sensitivity when inductively coupled to a broadband pick-up coil. Here, we demonstrated the coil's performance in hyperpolarized 13 C MRSI of a normal mouse and a glioblastoma mouse model at 4.7 T. High SNR exceeding 70:1 was obtained in the brain with good spatial resolution (1.53 mm × 1.53 mm). Similar inductively coupled loop for other X-nuclei can be made very easily in a few minutes and achieve high performance, as demonstrated in 31 P spectroscopy. Similar design concept was expanded to splitable, inductively coupled volume coils for high-resolution proton MRI of marmoset at 3T and 9.4T, to easily accommodate head restraint, vital-sign monitoring, and anesthesia delivery.

Development of Dissolution Dynamic Nuclear Polarization of [15 N3 ]Metronidazole: A Clinically Approved Antibiotic.

We report dissolution Dynamic Nuclear Polarization (d-DNP) of [15 N3 ]metronidazole ([15 N3 ]MNZ) for the first time. Metronidazole is a clinically approved antibiotic, which can be potentially employed as a hypoxia-sensing molecular probe using 15 N hyperpolarized (HP) nucleus. The DNP process is very efficient for [15 N3 ]MNZ with an exponential build-up constant of 13.8 min using trityl radical. After dissolution and sample transfer to a nearby 4.7 T Magnetic Resonance Imaging scanner, HP [15 N3 ]MNZ lasted remarkably long with T1 values up to 343 s and 15 N polarizations up to 6.4 %. A time series of HP [15 N3 ]MNZ images was acquired in vitro using a steady state free precession sequence on the 15 NO2 peak. The signal lasted over 13 min with notably long T2 of 20.5 s. HP [15 N3 ]MNZ was injected in the tail vein of a healthy rat, and dynamic spectroscopy was performed over the rat brain. The in vivo HP 15 N signals persisted over 70 s, demonstrating an unprecedented opportunity for in vivo studies.

Inversion of Hyperpolarized 13C NMR Signals through Cross-Correlated Cross-Relaxation in Dissolution DNP Experiments.

Dissolution dynamic nuclear polarization (DDNP) is a versatile tool to boost signal amplitudes in solution-state nuclear magnetic resonance (NMR) spectroscopy. For DDNP, nuclei are spin-hyperpolarized "ex situ" in a dedicated DNP device and then transferred to an NMR spectrometer for detection. Dramatic signal enhancements can be achieved, enabling shorter acquisition times, real-time monitoring of fast reactions, and reduced sample concentrations. Here, we show how the sample transfer in DDNP experiments can affect NMR spectra through cross-correlated cross-relaxation (CCR), especially in the case of low-field passages. Such processes can selectively invert signals of 13C spins in proton-carrying moieties. For their investigations, we use schemes for simultaneous or "parallel" detection of hyperpolarized 1H and 13C nuclei. We find that 1H → 13C CCR can invert signals of 13C spins if the proton polarization is close to 100%. We deduce that low-field passage in a DDNP experiment, a common occurrence due to the introduction of so-called "ultra-shielded" magnets, accelerates these effects due to field-dependent paramagnetic relaxation enhancements that can influence CCR. The reported effects are demonstrated for various molecules, laboratory layouts, and DDNP systems. As coupled 13C-1H spin systems are ubiquitous, we expect similar effects to be observed in various DDNP experiments. This might be exploited for selective spectroscopic labeling of hydrocarbons.

Effects of Microwave Gating on Nuclear Spin Echoes in Dynamic Nuclear Polarization.

Dipolar or quadrupolar echoes allow one to observe undistorted powder patterns, in contrast to simple Fourier transformations of free induction decays (FIDs). In this work, the buildup of proton polarization due to dynamic nuclear polarization (DNP) is monitored by observing echoes rather than FIDs. When the microwave irradiation is interrupted during the buildup of DNP, the electrons relax back to their Boltzmann distribution at high fields (B0 = 6.7 T) and low temperatures 1.2 < Tsample < 4.0 K, so that dipolar flip-flop-flip terms involving two electrons and one proton become largely ineffective as a mechanism of proton decoherence. This leads to a prolongation of the nuclear coherence lifetime T2'(1H). The increase in T2'(1H) leads to transient surges of the amplitudes of spin echoes. Conversely, transient slumps of spin echoes are observed when the microwave irradiation is switched back on, due to a shortening of nuclear coherence lifetimes.

Parkinson's disease and cancer: a systematic review and meta-analysis of over 17 million participants.

OBJECTIVE: To systematically review and qualitatively evaluate epidemiological evidence on associations between Parkinson's disease (PD) and cancer via meta-analysis. DATA SOURCES: MEDLINE via PubMed, Web of Science and EMBASE, until March 2021. STUDY SELECTION: Included were publications that (1) were original epidemiological studies on PD and cancer; (2) reported risk estimates; (3) were in English. Exclusion criteria included: (1) review/comments; (2) biological studies; (3) case report/autopsy studies; (4) irrelevant exposure/outcome; (5) treated cases; (6) no measure of risk estimates; (7) no confidence intervals/exact p values and (8) duplicates. DATA EXTRACTION AND SYNTHESIS: PRISMA and MOOSE guidelines were followed in data extraction. Two-step screening was performed by two authors blinded to each other. A random-effects model was used to calculate pooled relative risk (RR). MAIN OUTCOMES AND MEASURES: We included publications that assessed the risk of PD in individuals with vs without cancer and the risk of cancer in individuals with vs without PD. RESULTS: A total of 63 studies and 17 994 584 participants were included. Meta-analysis generated a pooled RR of 0.82 (n=33; 95% CI 0.76 to 0.88; p<0.001) for association between PD and total cancer, 0.76 (n=21; 95% CI 0.67 to 0.85; p<0.001) for PD and smoking-related cancer and 0.92 (n=19; 95% CI 0.84 to 0.99; p=0.03) for non-smoking-related cancer. PD was associated with an increased risk of melanoma (n=29; pooled RR=1.75; 95% CI 1.43 to 2.14; p<0.001) but not for other skin cancers (n=17; pooled RR=0.90; 95% CI 0.60 to 1.34; p=0.60). CONCLUSIONS: PD and total cancer were inversely associated. This inverse association persisted for both smoking-related and non-smoking-related cancers. PD was positively associated with melanoma. These results provide evidence for further investigations for possible mechanistic associations between PD and cancer. PROSPERO REGISTRATION NUMBER: CRD42020162103.

Transport of hyperpolarized samples in dissolution-DNP experiments.

Dissolution dynamic nuclear polarization (D-DNP) experiments rely on the transfer of a sample between two high-field magnets. During this transfer, samples might experience passage through regions where the stray fields of the magnets are very weak, can approach zero, and even change their sign. This can lead to unexpected spectral features in spin systems that undergo transitions from weak- to strong-coupling regimes and vice versa, much like in field cycling nuclear magnetic resonance experiments. We herein demonstrate that the spectral features observed in D-DNP experiments can be rationalized, provided the time-dependence of the spin Hamiltonian upon field cycling is sufficiently adiabatic. Under such conditions, a passage through a weak static field can lead to the emergence of a long-lived state (LLS) based on an imbalance between the populations of singlet and triplet states in pairs of nuclei that are strongly coupled during the passage through low field. The LLS entails the appearance of anti-phase multiplet components upon transfer to a high-field magnet for observation of NMR signals.

Relaxation of long-lived modes in NMR of deuterated methyl groups.

Long-lived imbalances of spin state populations can circumvent fast quadrupolar relaxation by reducing effective longitudinal relaxation rates by about an order of magnitude. This opens new avenues for the study of dynamic processes in deuterated molecules. Here we present an analysis of the relaxation properties of deuterated methyl groups CD3. The number of coupled equations that describe cross-relaxation between the 27 symmetry-adapted spin states of a D3 system can be reduced to only 2 non-trivial "lumped modes" by (i) taking the sums of the populations of all states that equilibrate rapidly within each irreducible representation of the symmetry group, and (ii) by combining populations that have similar relaxation rates although they belong to different irreducible representations. The quadrupolar relaxation rates of the spin state imbalances in CD3 groups are determined not by the correlation time of overall tumbling of the molecule, but by the frequency of jumps of methyl groups about their three-fold symmetry axis. We access these states via dissolution dynamic nuclear polarization (D-DNP), a method that allows one to populate the desired long-lived states at cryogenic temperatures and their subsequent detection at ambient temperatures after rapid dissolution. Experimental examples of DMSO-d6 and ethanol-d6 demonstrate that long-lived deuterium spin states are indeed accessible and that their lifetimes can be determined. Our analysis of the system via "lumped" modes allows us to visualize different possible spin-state populations of symmetry A, B, or E. Thus, we identify a long-lived spin state involving all three deuterons in a CD3 group as an A/E imbalance that can be populated through DNP at low temperatures.

A Report of 736 High-Definition Lipoabdominoplasties Performed in Conjunction with Circumferential VASER Liposuction.

BACKGROUND: Several innovations and modifications to the abdominal lipectomy procedure have been performed through the years. Despite recent improvements, the lack of natural results, including high scars, navel deformities, and "tense" abdomen, are still challenging. The objective of this study is to present an alternative technique of combined 360-degree truncal liposuction with abdominal definition, abdominoplasty, and neoumbilicoplasty. METHODS: From January of 2005 to June of 2017, 736 VASER-assisted lipoabdominoplasties were performed. Only healthy women with a body mass index below 33 were included. A three-step procedure was performed: (1) truncal liposculpture, (2) dermolipectomy and plication of the rectus abdominis muscle, and (3) neoumbilicoplasty through a butterfly technique. The follow-up included photographs and medical assessment with a mean of 2 years (up to 5 years). A nonstandardized survey was performed to self-evaluate the results. RESULTS: Six hundred seventy patients answered the survey (91 percent). Six hundred fifteen patients were satisfied with the procedure (91.79 percent). Minor complications were reported: seroma in 7.3 percent, prolonged bruising in 10 percent, and swelling in 18 percent. Neither flap necrosis nor infections were reported. Neoumbilicoplasty was performed in all patients. Additional procedures were required in 4.6 percent. CONCLUSIONS: Ultrasound-assisted lipoabdominoplasty is an alternative lipectomy technique that prevents stigmata of the procedure. The abdominal definition improves the shape and recreates the superficial anatomy. Neoumbilicoplasty shape, form, and choice of its position over the abdominal wall provide significant improvements in results. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Characterizing Thermal Mixing Dynamic Nuclear Polarization via Cross-Talk between Spin Reservoirs.

Dynamic nuclear polarization (DNP) embraces a family of methods to increase signal intensities in nuclear magnetic resonance (NMR) spectroscopy. Despite extensive theoretical work that allows one to distinguish at least five distinct mechanisms, it remains challenging to determine the relative weights of the processes that are responsible for DNP in state-of-the-art experiments operating with stable organic radicals like nitroxides at high magnetic fields and low temperatures. Specifically, determining experimental conditions where DNP involves thermal mixing, which denotes a spontaneous heat exchange between different spin reservoirs, remains challenging. We propose an experimental approach to ascertain the prevalence of the thermal mixing regime by monitoring characteristic signature properties of the time evolution of the hyperpolarization. We find that thermal mixing is the dominant DNP mechanism at high nitroxide radical concentrations, while a mixture of different mechanisms prevails at lower concentrations.