Signal enhancement through heteronuclear polarisation transfer in in-vivo <Superscript>31</Superscript>P MR spectroscopy of the human brain

Significant ³¹P NMR signal enhancement through heteronuclear polarisation transfer was obtained in model solutions and in vivo on a 1.5-T whole-body MR scanner equipped with two RF channels. The much higher population differences involved in proton Zeeman energy levels can be transferred to the ³¹P levels with the refocused INEPT (insensitive nucleus enhancement by polarisation transfer) double-resonance experiment by means of a series of simultaneously applied broadband RF pulses. INEPT achieves a polarisation transfer from ¹H to ³¹P spin states by directly reordering the populations in spin systems with heteronuclear scalar coupling. Thus, only the ³¹P NMR signal of metabolites with scalar ¹H–³¹P coupling is amplified, while the other metabolite signals in the spectra are suppressed. Compared to Ernst-angle excitation, a repetition-time-dependent signal enhancement of η=(29±3)% for methylene diphosphonic acid (MDPA) and η=(56±1)% for phosphorylethanolamine (PE) was obtained on model solutions through optimisation of the temporal parameters of the pulse experiment. The results are in good agreement with numerical calculations of the theoretical model for the studied spin systems. With optimised echo times, in-vivo ³¹P signal enhancement of the same order was obtained in studies of the human brain.     

Transmit/receive headcoil for optimal <Superscript>1</Superscript>H MR spectroscopy of the brain in paediatric patients at 3 T

¹H magnetic resonance (MR) spectroscopy is a useful tool to obtain metabolic information from the brain in paediatric patients. To detect signals of metabolites at low concentrations or from small volumes, the signal-to-noise ratio (SNR) has to be optimized. The SNR can be increased by going to higher field strengths. However, this leads to higher spectral bandwidths, which increases the chemical shift artefact. Here we present a transmit/receive headcoil which is adapted to the dimensions of the paediatric head and enables PRESS localization with high radio-frequency (RF) bandwidths that minimize the chemical shift displacement to only 5%. In addition, since the pulse lengths are shorter with higher RF bandwidths, the echo time can be reduced to 10 ms improving SNR as well.Parts of this work have been presented at the European Society for Magnetic Resonance in Medicine and Biology in Rotterdam in 2003     

Versatile coil design and positioning of transverse-field RF surface coils for clinical 1.5-T MRI applications

Clinical MRI/MRS applications require radio frequency (RF) surface coils positioned at an arbitrary angle with respect to B₀. In these experimental conditions the standard circular loop (CL) coil, producing an axial RF field, shows a large signal loss in the central region of interest (ROI). We demonstrate that transverse-field figure-of-eight (FO8) RF surface coils design are not subject to the same amount of signal loss in the central ROI as loop coils when their orientations are changed. The 1.5-T CL and FO8 prototypes (diameter = 10 cm) were built on Plexiglas using copper strips (width = 4 mm, thickness = 100 m). The two linear elements of the FO8 coil were 1 cm apart. Axial spoiled gradient echo (SPGR) images of a phantom containing doped water were acquired with the coil plane at =0°, 45°, and 90°. As increases, the CL images show, in the central ROI, a signal that decreases from a maximum value to zero. Whereas the FO8 images show, in the same ROI, a signal that varies little from the maximum value (20%). Optimized FO8 coils can be oriented with the coil plane positioned along any direction with respect to B₀ without significant signal loss. Transverse RF coil design should be useful for clinical MRS studies and also for parallel imaging techniques where versatile RF coils disposed along arbitrary directions are required.     

Hyperpolarized <Superscript>3</Superscript>He lung ventilation imaging with <Emphasis Type="Italic">B</Emphasis><Subscript>1</Subscript>-inhomogeneity correction in a single breath-hold scan

The signal-to-noise ratio (SNR) of hyperpolarized noble gas MR images is sensitive to the flip angle used. Variations in flip angle due to B ₁-inhomogeneity of the RF coil cause intensity variation artifacts in lung ventilation images which may mask or mimic disease. We show these artifacts can be minimized by using the optimal flip angle and corrected if the local flip angle is known. Hyperpolarized ³He lung images were obtained in ten healthy subjects using both a conventional gradient-echo sequence and a new hybrid pulse sequence designed to simultaneously acquire lung ventilation images and corresponding flip-angle maps in comparable imaging time. Flip-angle maps and corrected images were calculated from the hybrid scan and compared with conventional images. The qualitative theoretical dependence of flip angle on SNR was verified. Ventilation images and flip-angle maps were successfully obtained with the hybrid sequence. Corrections to image intensity calculated from the flip-angle maps appeared reasonable for images acquired using an average flip angle near optimal. Use of the optimal flip angle is crucial to the quality of lung ventilation images. Artifactual intensity variations due to RF-coil inhomogeneity may be identified and potentially corrected using our hybrid sequence. Acknowledgement The authors thank John M. Christopher, RT(R)(MR) for valuable assistance performing the studies, and Jaime F. Mata, MS, Jing Cai, MS, and Andrew G. Reish, BS, for excellent operation of the ³He polarization system. We gratefully acknowledge support for this research from the Commonwealth of Virginia Technology Research Fund (Grant No. IN2002-01), Siemens Medical Solutions and Amersham Health.     

Measurements of T1 and T2 relaxation times of colon cancer metastases in rat liver at 7 T

The purpose of this study was to investigate the magnetic resonance imaging (MRI) characteristics of colon cancer metastases in rat liver at 7 T. A dedicated RF microstrip coil of novel design was built in order to increase the signal-to-noise ratio and, in combination with respiratory triggering, to minimize motion artifacts. T₁- and T₂-weighted MR imaging was performed to follow tumor growth. T₁-weighted images provided a good anatomical delineation of the liver structure, while the best contrast between metastases and normal liver tissue was achieved with T₂-weighted images.Measurements of T₁ and T₂ relaxation times were performed with inversion recovery FLASH and Carr–Purcell–Meiboom–Gill and inversion recovery FLASH imaging sequences, respectively, for quantitative MR characterization of metastases. Both the T₁ and T₂ of the metastases were significantly higher than those of normal liver tissue. Further, an increase in the T₁ relaxation time of the metastases was observed with tumor growth. These findings suggest that quantitative in vivo MR characterization provides information on tumor development and possibly response to therapy, though additional studies are needed to elucidate the correlation between the changes in relaxation times and tumor microenvironment.     

A simple method for mapping the B1 field distribution of linear RF coils

Inhomogeneity of the radio frequency (RF) field B₁ leads to intensity variations in MR images and to spatial dependence of spectral line amplitudes. In this paper, a simple method of measuring the B₁ field components of an unsegmented linear coil is described. The method is designed for the coils operating up to 20 MHz. The B₁ field distribution is replaced by the static magnetic field caused by DC current flowing through the coil. The technique involves rotating the coil 90° so that measured B₁ component is aligned with B₀ and measuring the shift of resonance frequency using a spectroscopic imaging sequence. Experimental results were in good agreement with the theoretical computations.     

Quality assurance of PASADENA hyperpolarization for 13C biomolecules

Object  Define MR quality assurance procedures for maximal PASADENA hyperpolarization of a biological ¹³C molecular imaging reagent. Materials and methods  An automated PASADENA polarizer and a parahydrogen generator were installed. ¹³C enriched hydroxyethyl acrylate, 1-¹³C, 2,3,3-d₃ (HEA), was converted to hyperpolarized hydroxyethyl propionate, 1-¹³C, 2,3,3-d₃ (HEP) and fumaric acid, 1-¹³C, 2,3-d₂ (FUM) to hyperpolarized succinic acid, 1-¹³C, 2,3-d₂ (SUC), by reaction with parahydrogen and norbornadiene rhodium catalyst. Incremental optimization of successive steps in PASADENA was implemented. MR spectra and in vivo images of hyperpolarized ¹³C imaging agents were acquired at 1.5 and 4.7 T. Results  Application of quality assurance (QA) criteria resulted in incremental optimization of the individual steps in PASADENA implementation. Optimal hyperpolarization of HEP of P = 20% was achieved by calibration of the NMR unit of the polarizer (B ₀ field strength ± 0.002 mT). Mean hyperpolarization of SUC, P = [15.3 ± 1.9]% (N = 16) in D ₂O, and P = [12.8 ± 3.1]% (N = 12) in H ₂O, was achieved every 5–8 min (range 13–20%). An in vivo ¹³C succinate image of a rat was produced. Conclusion  PASADENA spin hyperpolarization of SUC to 15.3% in average was demonstrated (37,400 fold signal enhancement at 4.7 T). The biological fate of ¹³C succinate, a normally occurring cellular intermediate, might be monitored with enhanced sensitivity.     

Microwave dielectric properties of Na<Superscript>+</Superscript> and M<Superscript>3+</Superscript>-doped Ba(Mg<Subscript>0.5</Subscript>W<Subscript>0.5</Subscript>)O<Subscript>3</Subscript> ceramics

In this study, phase evolution, microstructure, and microwave dielectric properties of (Ba_0.98Na_0.02)(Mg_0.48M³⁺_0.02W_0.5)O₃ (M³⁺?=?Al, Ga, Sc, In, Yb, Y, Dy, Gd, and Sm) ceramics sintered at 1700 °C for 1 h were investigated. All the compounds exhibited an ordered cubic perovskite structure. Regardless of the ionic radius of the doped M³⁺ ions, BaWO₄ was detected as the secondary phase in all the compounds. The field emission scanning electron microscopy (FE-SEM) images revealed a dense microstructure in all the compounds, except in the Al-doped compound, which exhibited an insufficient grain growth. The large and irregularly shaped grains indicated that the liquid phase sintering occurred. Splitting of the A_1g(O) mode was observed in the Raman spectra of large M³⁺ ion-doped compounds. Splitting of the F_2g modes did not occur and the bands were sharp, indicating that the cubic symmetry was retained. As the ionic radius of the doped M³⁺ ions increased, the dielectric constant (ε_r) increased slightly. The compounds doped with M³⁺?=?Sc, In, Yb, and Y exhibited a very high quality factor (Q?×?f₀) in the range of 250,000 ~ 280,000 GHz. In the case of the compounds doped with M³⁺?=?Al, Ga, Sc, In, Yb, Y, and Dy, the value of the temperature coefficient of resonant frequency (τ_f) was in the range of ?24 ~ ?19 ppm/°C, while the Gd and Sm-doped compounds exhibited positive values of 2.8 and 31.2 ppm/°C, respectively. The dielectric constant, quality factor, and temperature coefficient of resonant frequency of the In-doped compound, i.e., (Ba_0.98Na_0.02)(Mg_0.48In_0.02W_0.5)O₃, were 18.7, 286,557 GHz, and???24.4 ppm/°C, respectively.     

<Superscript>1</Superscript>H MR spectroscopy as a diagnostic tool for cerebral creatine deficiency

Objective  Total creatine (tCr) constitutes one of the most prominent signals in human brain MR spectra. A significant decrease in the tCr signal indicates a severe disorder of creatine metabolism. We describe the potential of ¹H MR spectroscopy in differential diagnosis of creatine transporter (SLC6A8) deficiency syndrome. Materials and methods  Two siblings, a 7-year-old female presenting with mild psychomotor delay, and a 5-year-old male with severe psychomotor retardation, epilepsy and autistic spectrum of problems including speech delay, underwent MR examination because of suspected creatine deficiency. After the MRI examination, ¹H MR spectroscopy using the CSI technique was performed. Results  Metabolic images of N-acetylaspartate, tCr and choline concentrations showed a very low tCr signal in the male, which was approximately three times lower than in his sister (male/female/controls: tCr = 1.6/4.6/7.5 mM). Despite creatine supplementation, no improvement in clinical status and tCr concentration in the MR spectra of the male was observed and diagnosis of SLC6A8 deficiency was proposed. Sequence analysis of the SLC6A8 gene revealed a novel pathogenic frameshift mutation c.219delC; p.Asn74ThrfsX23, hemizygous in the male and heterozygous in the female. Conclusions  The diagnosis of X-linked mental retardation caused by the SLC6A8 deficiency can be independently established by ¹H MR spectroscopy.     

Effects of Al<Superscript>3+</Superscript> substitution on the luminescence properties of LuNbO<Subscript>4</Subscript> doped with Eu<Superscript>3+</Superscript> and Tb<Superscript>3+</Superscript> ions

The effect of Al³⁺ substitution on the enhancement of the luminescence of Lu_1–xAl_xNbO₄:Eu³⁺ and Lu_1–xAl_xNbO₄:Tb³⁺ was investigated. X-ray diffraction patterns confirmed that the Eu³⁺, Tb³⁺, and Al³⁺ ions were fully incorporated into the Lu³⁺ sites. In the case of Lu_1–xAl_xNbO₄:Eu³⁺, the predominant red emission (614 nm) was assigned to the ⁵D₀?→?⁷F₂ transition of Eu³⁺ and for x?=?0–0.05, its intensity increased up to ~125 and 108% under 395 nm (⁷F₀ → ⁵L₆) and a charge transfer band excitation, respectively. For Lu_1–xAl_xNbO₄:Tb³⁺, the strongest emission band peaking at 551 nm was attained in the green region among multiple emission bands corresponding to the ⁵D₄?→?⁷F_J transitions of Tb³⁺. Increasing the x values from 0 to 0.05 increased the green emission significantly by ~137%. These phenomena were explained by the local structural distortions and crystal field asymmetry surrounding Eu³⁺ and Tb³⁺, which were attributed to a large difference in the ionic radii of Al³⁺ and Lu³⁺.     

Microwave Dielectric Properties of CuO-V<Subscript>2</Subscript>O<Subscript>5</Subscript>-Bi<Subscript>2</Subscript>O<Subscript>3</Subscript>-Doped ZnNb<Subscript>2</Subscript>O<Subscript>6</Subscript> Ceramics with Low Sintering Temperature

Microwave dielectric properties of low temperature sintering ZnNb₂O₆ ceramics doped with CuO-V₂O₅-Bi₂O₃ additions were investigated systematically. The co-doping of CuO, V₂O₅ and Bi₂O₃ can significantly lower the sintering temperature of ZnNb₂O₆ ceramics from 1150 to 870C. The secondary phase containing Cu, V, Bi and Zn was observed at grain boundary junctions, and the amount of secondary phase increased with increasing CuO-V₂O₅-Bi₂O₃ content. The dielectric properties at microwave frequencies (7–9 GHz) in this system exhibited a significant dependence on the relative density, content of additives and microstructure of the ceramics. The dielectric constant ( _r) of ZnNb₂O₆ ceramics increased from 21.95 to 24.18 with increasing CuO-V₂O₅-Bi₂O₃ additions from 1.5 to 4.0 wt%. The quality factors (Q× f) of this system decreased with increasing CuO-V₂O₅-Bi₂O₃ content and ranged from 36118 to 67100 GHz for sintered ceramics, furthermore, all Q× f values of samples with CuO-V₂O₅-Bi₂O₃ additions are lower than that of un-doped ZnNb₂O₆ ceramics sintered at 1150C for 2 h. The temperature coefficient of resonant frequency ( _f) changed from –33.16 to –25.96 ppm/C with increasing CuO-V₂O₅-Bi₂O₃ from 1.5 to 4.0 wt%     

Assignment of the 2.03 ppm resonance in in vivo <Superscript>1</Superscript>H MRS of human brain tumour cystic fluid: contribution of macromolecules

MRI and MRS are established techniques for the evaluation of intracranial mass lesions and cysts. The 2.03 ppm signal recorded in their ¹H-MRS spectra is often assigned to NAA from outer volume contamination, although it has also been detected in non-infiltrating tumours and large cysts. We have investigated the molecular origin of this resonance in ten samples of cystic fluids from human brain tumours. The NMR detected content of the 2.03 ppm resonance in 136 ms echo time spectra, assuming an N- CH₃ origin, was 3.19 ± 1.01 mM. Only one third (34 ± 12%) of the N-acetyl containing compound (NAC) signal could be extracted by perchloric acid (PCA) indicating that most of it originated in a macromolecular PCA-insoluble component. Chemical analysis of the cyst fluids showed that sialic acid bound to macromolecules would account for 64.3% and hexuronic containing compounds for 29.2% of the NMR-detectable ex vivo signal, 93.4% of the signal at TE 136 ms. Lactate content measured by NMR (6.4 ± 4.4 mM) and the predominance of NAC originating in sialic acid point to a major origin from tumour rather than from plasma for this 2.03 ppm resonance.     

Dielectric and Piezoelectric Properties of Na<Subscript>0.5</Subscript>Bi<Subscript>0.5</Subscript>TiO<Subscript>3</Subscript>-K<Subscript>0.5</Subscript>Bi<Subscript>0.5</Subscript>TiO<Subscript>3</Subscript>-NaNbO<Subscript>3</Subscript>Lead-Free Ceramics

The ternary lead-free piezoelectric ceramics system of (1 – x) [0.88Na_0.5Bi_0.5TiO₃-0.12K_0.5Bi_0.5TiO₃] – xNaNbO₃(x = 0, 0.02, 0.04, 0.06, 0.08, 0.10) were synthesized by conventional solid state reaction method. The crystal structure, dielectric, piezoelectric properties and P-E hysteresis loops were investigated. The crystalline structure of all compositions is mono-perovskite phase ascertained by XRD, and the lattice constant was calculated from the XRD data. Temperature dependence of dielectric constant _r and dissipation factor tan measurement revealed that all compositions experienced two phase transitions: from ferroelectric to anti-ferroelectric and from anti-ferroelectric to paraelectric, and these two phase transitions have relaxor characteristics. Both transition temperatures T_d and T_m are lowered due to introduction of NaNbO₃. P-E hysteresis loops show that 0.88Na_0.5Bi_0.5TiO₃-0.12K_0.5Bi_0.5TiO₃ ceramics has the maximum P_r and E_c corresponding to the maximum values of electromechanical coupling factor K_p and piezoelectric constant d_33. The piezoelectric constant d₃₃ and electromechanical coupling factor K_p decrease a little, while the dielectric constant ₃₃^T/₀ improves much more when the concentration of NaNbO₃ is 8 mol%.     

Site Preference of La in Bi<Subscript>3.75</Subscript>La<Subscript>0.25</Subscript>Ti<Subscript>3</Subscript>O<Subscript>12</Subscript> Using Neutron Powder Diffraction and Raman Scattering

Both structural refinement using neutron powder diffraction data and Raman scattering were carried out to determine the site preference of La atoms and the cation distribution in Bi_3.75La_0.25Ti₃O₁₂ compound. Of three possible cation-disorder models, the best structural refinement result was obtained from a model that La atoms substitute only for Bi atoms outside of the TiO₆ octahedra in the Bi₂Ti₃O₁₀ unit. The model proposed by the structural refinement was corroborated by the Raman spectroscopic study. The final weighted R-factor, R_wp, and the goodness-of-fit indicator, S (= R_wp/R_e), based on the neutron diffraction and the Raman scattering were 4.12% and 1.43, respectively. The occupancy of La atoms for two Bi sites in the perovskite-like unit was 0.082 and 0.074, respectively. The refined model described a structure in monoclinic space group B1a1 with Z = 4, a = 5.4387(1) Å, b = 5.4129(1) Å, c = 32.8441(1) Å and = 90.03(1).     

Low Temperature Sintering of BaTi<Subscript>4</Subscript>O<Subscript>9</Subscript>-Based Middle-<Emphasis Type="Italic">k</Emphasis> Dielectric Composition for LTCC Applications

Effect of glass addition on the low-temperature sintering and microwave dielectric properties of BaTi₄O₉-based ceramics were studied to develop the middle-k dielectric composition for the functional substrate of low-temperature co-fired ceramics. When 10 wt% of glass was added, sufficient densification was obtained and the relative density more than 98% was reached at the sintering temperature of 875C. The microwave dielectric properties were k = 32, Q × f = 9000 GHz, and t_cf = 10 ppm/C. As the added amount of glass frit with base dielectric composition, phase changes from BaTi₄O₉ to BaTi₅O₁₁ and Ba₄Ti₁₃O₃₀ was observed, which result in the modification of microwave dielectric properties.     

Dielectric Properties and Sintering Characteristics of CaTiO<Subscript>3</Subscript>-(Li<Subscript>1/2</Subscript>Nd<Subscript>1/2</Subscript>)TiO<Subscript>3</Subscript> Ceramics

The dielectric properties and the sintering effect upon microstructure of (1–x) CaTiO₃-x(Li_1/2Nd_1/2)-TiO₃ Ceramics are investigated in this paper. Nd³⁺ and Mg^{2 +} ions co-substitution for Ca^{2 +} on A site improves the sintering characteristic of CaTiO₃ ceramics with forming orthorhombic perovskite structure. The structure of (1 – x) CaTiO₃-x(Li_1/2Nd_1/2)TiO₃ changes from orthorhombic to tetragonal as (Li_1/2Nd_1/2)TiO₃ addition increasing. Limited solubility of (Li_1/2Nd_1/2)TiO₃ in CaTiO₃ forming a part solid solution compound achieves the adjustment of for CaTiO₃ at low sintering temperature. The proper dielectric properties with = 78, tan = 0.0006, = +7 ppm/C are obtained for 0.8Ca_0.67(Nd,Mg)_0.22TiO₃-0.2(Li_1/2Nd_1/2)TiO₃ ceramics.     

Imaging lung function using rapid dynamic acquisition of <Emphasis Type="Italic">T</Emphasis><Subscript>1</Subscript>-maps during oxygen enhancement

This paper describes imaging of lung function with oxygen-enhanced MRI using dynamically acquired T ₁ parameter maps, which allows an accurate, quantitative assessment of time constants of T ₁-enhancement and therefore lung function. Eight healthy volunteers were examined on a 1.5-T whole-body scanner. Lung T ₁-maps based on an IR Snapshot FLASH technique (TE = 1.4 ms, TR = 3.5 ms, FA = 7 ^∘) were dynamically acquired from each subject. Without waiting for full relaxation between subsequent acquisition of T ₁-maps, one T ₁-map was acquired every 6.7 s. For comparison, all subjects underwent a standard pulmonary function test (PFT). Oxygen wash-in and wash-out time course curves of T ₁ relaxation rate (R ₁)-enhancement were obtained and time constants of oxygen wash-in (w _in) and wash-out (w _out) were calculated. Averaged over the whole right lung, the mean w _out was 43.90 ± 10.47 s and the mean (w _in) was 51.20 ± 15.53 s, thus about 17% higher in magnitude. Wash-in time constants correlated strongly with forced expired volume in one second in percentage of the vital capacity (FEV₁ % VC) and with maximum expiratory flow at 25% vital capacity (MEF25), whereas wash-out time constants showed only weak correlation. Using oxygen-enhanced rapid dynamic acquisition of T ₁-maps, time course curves of R ₁-enhancement can be obtained. With w _in and w _out two new parameters for assessing lung function are available. Therefore, the proposed method has the potential to provide regional information of pulmonary function in various lung diseases.     

Dual resonant birdcage coils for1H detected13C microscopic imaging at 11.7 T

Liquid state, rotating frame cross polarisation experiments are very sensitive to RF field inhomogeneity. In this work, we present an easily fabricated, co-resident high- and low-pass linear birdcage resonator, optimised to perform liquid state rotating frame polarisation transfer at¹H and¹³C frequencies. Both the RF fields have been experimentally mapped, and used to validate the spatial signal dependence of a proton detected,¹³C image. The predicted performance was then confirmed using PRAWN-based, cyclic J-cross polarisation (CYCLCROP) imaging. A novel variant of a B₁-field mapping approach is also presented, using the signal enhancement of the CYCLCROP sequence to generate proton detected,¹³C field maps.     

B1 field-insensitive transformers for RF-safe transmission lines

Objective: Integration of transformers into transmission lines suppresses radiofrequency (RF)-induced heating. New figure-of-eight-shaped transformer coils are compared to conventional loop transformer coils to assess their signal transmission properties and safety profile. Materials and methods: The transmission properties of figure-of-eight-shaped transformers were measured and compared to transformers with loop coils. Experiments to quantify the effect of decoupling from the B₁ field of the MR system were conducted. Temperature measurements were performed to demonstrate the effective reduction of RF-induced heating. The transformers were investigated during active tracking experiments. Results: Coupling to the B₁ field was reduced by 18 dB over conventional loop-shaped transformer coils. MR images showed a significantly reduced artifact for the figure-of-eight- shaped coils generated by local flip-angle amplification. Comparable transmission properties were seen for both transformer types. Temperature measurements showed a maximal temperature increase of 30K/3.5 K for an unsegmented/ segmented cable. With a segmented transmission line a robotic assistance system could be successfully localized using active tracking. Conclusion: The figure-of-eight-shaped transformer design reduces both RF field coupling with the MR system and artifact sizes. Anatomical structure close to the figure-of-eight-shaped transformer may be less obscured as with loop-shaped transformers if these transformers are integrated into e.g. intravascular catheters.     

Feasibility of in vivo three-dimensional T<Stack><Subscript>2</Subscript><Superscript>*</Superscript></Stack> mapping using dicarboxy-PROXYL and CW-EPR-based single-point imaging

Objectives

The aim of this study was to demonstrate the feasibility of in vivo three-dimensional (3D) relaxation time T ₂ ^* mapping of a dicarboxy-PROXYL radical using continuous-wave electron paramagnetic resonance (CW-EPR) imaging.

Materials and methods

Isotopically substituted dicarboxy-PROXYL radicals, 3,4-dicarboxy-2,2,5,5-tetra(²H₃)methylpyrrolidin-(3,4-²H₂)-(1-¹⁵N)-1-oxyl (²H,¹⁵N-DCP) and 3,4-dicarboxy-2,2,5,5-tetra(²H₃)methylpyrrolidin-(3,4-²H₂)-1-oxyl (²H-DCP), were used in the study. A clonogenic cell survival assay was performed with the ²H-DCP radical using squamous cell carcinoma (SCC VII) cells. The time course of EPR signal intensities of intravenously injected ²H,¹⁵N-DCP and ²H-DCP radicals were determined in tumor-bearing hind legs of mice (C3H/HeJ, male, n = 5). CW-EPR-based single-point imaging (SPI) was performed for 3D T ₂ ^* mapping.

Results

²H-DCP radical did not exhibit cytotoxicity at concentrations below 10 mM. The in vivo half-life of ²H,¹⁵N-DCP in tumor tissues was 24.7 ± 2.9 min (mean ± standard deviation [SD], n = 5). The in vivo time course of the EPR signal intensity of the ²H,¹⁵N-DCP radical showed a plateau of 10.2 ± 1.2 min (mean ± SD) where the EPR signal intensity remained at more than 90% of the maximum intensity. During the plateau, in vivo 3D T ₂ ^* maps with ²H,¹⁵N-DCP were obtained from tumor-bearing hind legs, with a total acquisition time of 7.5 min.

Conclusion

EPR signals of ²H,¹⁵N-DCP persisted long enough after bolus intravenous injection to conduct in vivo 3D T ₂ ^* mapping with CW-EPR-based SPI.