High-Contrast and Fast-Removable 19 F-MRI Labels with Perfluoro-tert-Butyl Substituents.

19 F MRI is a unique technique for tracking and quantifying the indicator (19 F-MRI label) in vivo without the use of ionizing radiation. Here we report new 19 F-MRI labels, which are compounds with perfluoro-tert-butyl groups: 1,2-bis(perfluoro-tert-butoxy)ethane (C10 F18 H4 O2 ) and 1,3-bis(perfluoro-tert-butyl)propane (C11 F18 H6 ). Both substances contain 18 equivalent 19 F atoms, constituting 68.67 % and 71.25 % of the molecule, respectively. The emulsions with 19 F molecules were prepared and used in 19 F MRI studies in laboratory rats in vivo. The substances demonstrated high contrast properties, good biological inertness and the ability to be rapidly eliminated from the body. We showed that at a dose of 0.34 mg/g of body weight in rats, the time for complete elimination of C10 F18 H4 O2 and C11 F18 H6 is ∼30 days. The results turned out to be promising for the use of the presented compounds in 19 F MRI applications, especially since they are quite easy to synthesize.

Т1 mapping of rat lungs in 19 F MRI using octafluorocyclobutane.

PURPOSE: To demonstrate the feasibility of using octafluorocyclobutane (OFCB, c-C4 F8 ) for T1 mapping of lungs in 19 F MRI. METHODS: The study was performed at 7 T in three healthy rats and three rats with pulmonary hypertension. To increase the sensitivity of 19 F MRI, a bent-shaped RF coil with periodic metal strips structure was used. The double flip angle method was used to calculate normalized transmitting RF field (B1n + ) maps and for correcting T1 maps built with the variable flip angle (VFA) method. The ultrashort TE pulse sequence was applied for acquiring MR images throughout the study. RESULTS: The dependencies of OFCB relaxation times on its partial pressure in mixtures with oxygen, air, helium, and argon were obtained. T1 of OFCB linearly depended on its partial pressure with the slope of about 0.35 ms/kPa in the case of free diffusion. RF field inhomogeneity leads to distortion of T1 maps built with the VFA method, and therefore to high standard deviation of T1 in these maps. To improve the accuracy of the T1 maps, the B1n + maps were applied for VFA correction. This contributed to a 2-3-fold decrease in the SD of T1 values in the corresponding maps compared with T1 maps calculated without the correction. Three-dimensional T1 maps were obtained, and the mean T1 in healthy rat lungs was 35 ± 10 ms, and in rat lungs with pulmonary hypertension - 41 ± 9 ms. CONCLUSION: OFCB has a spin-rotational relaxation mechanism and can be used for 19 F T1 mapping of lungs. The calculated OFCB maps captured ventilation defects induced by edema.

Mitochondrial peptide Mtln contributes to oxidative metabolism in mice.

Mitoregulin (Mtln) is a recently identified 56 amino acid long mitochondrial peptide conserved in vertebrates. Mtln is known to enhance function of respiratory complex I, which is likely mediated by modulation of lipid composition. To address an influence of Mtln gene on the metabolism we created knockout mice deficient in Mtln gene. In line with accumulation of triglycerides observed earlier on a model of Mtln knockout cell lines, we observed Mtln KO mice to develop obesity on a high fat diet. An increased weight gain could be attributed to enhanced fat accumulation according to the magnetic resonance live imaging. In addition, Mtln KO mice demonstrate elevated serum triglycerides and other oxidation substrates accompanied by an exhaustion of tricarboxylic acids cycle intermediates, suggesting suboptimal oxidation of respiration substrates by mitochondria lacking Mtln.

Design and first implementation of wireless square-shaped transmission line resonators in 1H MRI for small animal studies.

This work is dedicated to the development of a novel design for wireless transmission line resonators (TLRs). The TLRs are often considered as circular-shaped coils made up of two conductive circuits separated by a dielectric layer. We propose a square-shaped TLR design, wherein the coil has two square turns with two symmetrical gaps on each of the conductive layers, and the latter are rotated relative to each other by 90°. The calculation error of the resonant frequency of the square-shaped TLRs is no more than ∼3% of the measured value. The effectiveness of the square-shaped TLR design was evaluated in comparative 1H MRI studies to conventional wireless square loop of the same resonant frequency and with the same-sized inner square of the TLR. The Bruker birdcage was used as a transceiver and as inductively coupled with the wireless coils. We found that the performance of the square-shaped TLR and the square loop is comparable, but the B1+-field generated by the TLR has a wider distribution profile. It was reflected in rat brain studies, when some structures of rat head were not captured by the square loop. Comparative experiments with a standard circular-shaped TLR showed that a signal is predominantly concentrated inside the inner turn of the TLRs. The proposed TLR design can be a promising path to be explored, especially for scanning small objects of study, when the scan area is comparable to the size of the rigid lumped capacitors.

Three-dimensional fast single-point macromolecular proton fraction mapping of the human brain at 0.5 Tesla.

Fast single-point macromolecular proton fraction (MPF) mapping is a recent magnetic resonance imaging (MRI) method enabling quantitative assessment of myelin content in neural tissues. To date, the reported technical implementations of MPF mapping utilized high-field MRI equipment (1.5 T or higher), while low-field applications might pose challenges due to signal-to-noise ratio (SNR) limitations and short T1 . This study aimed to evaluate the feasibility of MPF mapping of the human brain at 0.5 T. The three-dimensional MPF mapping protocol was implemented according to the single-point synthetic-reference method, which includes three spoiled gradient-echo sequences providing proton density, T1 , and magnetization transfer contrast weightings. Whole-brain MPF maps were obtained from three healthy volunteers with spatial resolution of 1.5×1.5×2 mm3 and the total scan time of 19 minutes. MPF values were measured in a series of white and gray matter structures and compared with literature data for 3 T magnetic field. MPF maps enabled high contrast between white and gray matter with notable insensitivity to paramagnetic effects in iron-rich structures, such as globus pallidus, substantia nigra, and dentate nucleus. MPF values at 0.5 T appeared in close agreement with those at 3 T. This study demonstrates the feasibility of fast MPF mapping with low-field MRI equipment and the independence of brain MPF values of magnetic field. The presented results confirm the utility of MPF as an absolute scale for MRI-based myelin content measurements across a wide range of magnetic field strengths and extend the applicability of fast MPF mapping to inexpensive low-field MRI hardware.

19 F MRI of human lungs at 0.5 Tesla using octafluorocyclobutane.

PURPOSE: The aim of this study was to demonstrate the feasibility of fluorine-19 (19 F) MRI of the human lungs using octafluorocyclobutane (OFCB, C4 F8 ). This gas has 8 magnetically equivalent fluorine nuclei and relatively long T1 and T2 (˜50 ms), which render it suitable as an MRI contrast agent. Previous experiments in small laboratory animals showed that OFCB could be successfully used as an alternative to the gases often used for 19 F MRI (sulfur hexafluoride and perfluoropropane). METHODS: One male volunteer participated in this study. Immediately before an MRI scan, the volunteer inhaled the gas mixture-80% OFCB with 20% oxygen-and held his breath. Experiments were performed on a 0.5T whole-body MR scanner with a customized transmit-receive coil tuned at 19 F frequency. Fast spin echo in 2D and 3D modes was used for image acquisition. 2D images were obtained with in-plane resolution of 10 × 10 mm2 without slice selection. 3D images were obtained with the voxel size of 10 × 10 × 30 mm2 . Breath-hold duration was 20 s for 2D and 40 s for 3D imaging, respectively. RESULTS: Anatomically consistent 19 F MR images of the human lungs were obtained with SNR around 50 in 2D mode and 20 in 3D mode. 3D volumetric images of the lungs were reconstructed and provided physiologically reasonable volume estimates. CONCLUSION: The application of OFCB enables informative 19 F lung imaging even at low magnetic field strengths. The OFCB gas shows promise as an inhalable contrast agent for fluorine lung MRI and has a potential for clinical translation.

Application of copper plates for frequency tuning of surface wired and wireless MRI coils.

This study shows how a copper plate could be used for frequency tuning of surface wired and wireless MRI coils. For this purpose, it is proposed to place the copper plate directly on their conducting circuit. This leads to increase in the resonance frequency of coils. The effect is most perceptible if the copper plate is comparable in size to the conducting circuit of radiofrequency (RF) coil. The experimental work was performed on a 7.05 T MR scanner using surface MRI coils operating on different resonance frequencies: 1H (300 MHz), 31P (121 MHz), 23Na (79 MHz), 13C (75 MHz). Application of copper plate for frequency tuning of wireless multi-turn multi-gap transmission line resonator (MTMG-TLR) was considered for the first time. The proposed method can be claimed if the nominal variable inductance or capacitance is not enough for tuning the resonance frequency of the MRI coil to a higher frequency range.

Computation of the resonance frequencies of the transmission line resonators used in MRI.

Stripline high frequency resonators or transmission line resonators (TLRs) manufactured as concentric RF coils at the opposite sides of a dielectric sheet serve as wireless self-resonant transmitters-receivers in MRI. Owing to their high quality factor relative to traditional RF coils composed of bulk inductor and capacitors, frequency selectivity of TLRs is high, making them promising elements for single-nucleus MRI. However, the computation of their resonance frequencies is cumbersome, and numerous mathematical mistakes and typos in publications lead to incorrect results. The present publication is the first to summarize the corrected formulas for computations and presents comparison of such computations to real measurements.

Quantitative assessment of regulatory proteins in blood as markers of radiation effects in the late period after occupational exposure.

The objective of this research was quantitative assessment of serum and membrane regulatory proteins in blood from nuclear workers as markers of radiation-induced alterations in immune homeostasis in the late period after protracted exposure of nuclear workers with different doses. The effector and regulatory lymphocytes were measured using a flow cytofluorometer in workers from the main facilities of the Mayak PA (aged ∼60 y up to 80 y) in the late period after combined exposure to external gamma-rays and internal alpha-radiation from incorporated 239Pu. The control group included non-occupationally exposed members of the Ozyorsk population matched by gender and age to the group of Mayak workers. Thirty serum proteins involved in regulation of immune homeostasis, such as growth factors, multifunctional interleukins, pro- and anti-inflammatory cytokines, and their receptors, were measured using ELISA in blood serum specimens from the Radiobiology Human Tissue Repository. The dosimetry estimates were obtained using Doses-2005. The correlation analysis revealed a statistically significant direct relationship of T-killers and plutonium body burden and a decreasing level of T-helpers with accumulated external dose in exposed individuals. There were differences in expression of membrane markers in young regulatory cells (double null T-lymphocytes, NKT-lymphocytes, regulatory T-cells, and an increase of activated forms of T-lymphocytes), which indicated an active role of regulatory cells in maintaining immune homeostasis in terms of protracted exposure. The assessment of regulatory proteins in blood indicated that growth factors (EGF, TGF-ß1, PDGF), multifunctional interleukins (IL-17A, IL-18), and pro-inflammatory cytokines (IL-1ß and INF-γ) could be potential markers of radiation-induced alterations in protein status. An imbalance of pro- and antiinflammatory proteins in blood and variations of protein profiles at the lower exposure levels (gamma-ray dose <1 Gy, plutonium body burden <0.74 kBq) in the late period after protracted exposure were less pronounced than at the higher exposure levels, which was probably explained by compensatory-adaptive responses in the late period among senile individuals with polypathology.