Development of a 7 T RF coil system for breast imaging

In ultrahigh‐field MRI, such as 7 T, the signal‐to‐noise ratio (SNR) increases while transmit (Tx) field (B₁⁺) can be degraded due to inhomogeneity and elevated specific absorption rate (SAR). By applying new array coil concepts to both Tx and receive (Rx) coils, the B₁⁺ homogeneity and SNR can be improved. In this study, we developed and tested in vivo a new RF coil system for 7 T breast MRI. An RF coil system composed of an eight‐channel Tx‐only array based on a tic‐tac‐toe design (can be combined to operate in single‐Tx mode) in conjunction with an eight‐channel Rx‐only insert was developed. Characterizations of the B₁⁺ field and associated SAR generated by the developed RF coil system were numerically calculated and empirically measured using an anatomically detailed breast model, phantom and human breasts. In vivo comparisons between 3 T (using standard commercial solutions) and 7 T (using the newly developed coil system) breast imaging were made. At 7 T, about 20% B₁⁺ inhomogeneity (standard deviation over the mean) was measured within the breast tissue for both the RF simulations and 7 T experiments. The addition of the Rx‐only array enhances the SNR by a factor of about three. High‐quality MR images of human breast were acquired in vivo at 7 T. For the in vivo comparisons between 3 T and 7 T, an approximately fourfold increase of SNR was measured with 7 T imaging. The B₁⁺ field distributions in the breast model, phantom and in vivo were in reasonable agreement. High‐quality 7 T in vivo breast MRI was successfully acquired at 0.6 mm isotropic resolution using the newly developed RF coil system.     

Homogeneous B1+ for bilateral breast imaging at 7 T using a five dipole transmit array merged with a high density receive loop array

To explore the use of five meandering dipole antennas in a multi‐transmit setup, combined with a high density receive array for breast imaging at 7 T for improved penetration depth and more homogeneous B₁ field. Five meandering dipole antennas and 30 receiver loops were positioned on two cups around the breasts. Finite difference time domain simulations were performed to evaluate RF safety limits of the transmit setup. Scattering parameters of the transmit setup and coupling between the antennas and the detuned loops were measured. In vivo parallel imaging performance was investigated for various acceleration factors. After RF shimming, a B₁ map, a T₁‐weighted image, and a T₂‐weighted image were acquired to assess B₁ efficiency, uniformity in contrast weighting, and imaging performance in clinical applications. The maximum achievable local SAR_10g value was 7.0 W/kg for 5 × 1 W accepted power. The dipoles were tuned and matched to a maximum reflection of ?11.8 dB, and a maximum inter‐element coupling of ?14.2 dB. The maximum coupling between the antennas and the receive loops was ?18.2 dB and the mean noise correlation for the 30 receive loops 7.83 ± 8.69%. In vivo measurements showed an increased field of view, which reached to the axilla, and a high transmit efficiency. This coil enabled the acquisition of T₁‐weighted images with a high spatial resolution of 0.7 mm³ isotropic and T₂‐weighted spin echo images with uniformly weighted contrast.     

Low SAR 31P (multi‐echo) spectroscopic imaging using an integrated whole‐body transmit coil at 7T

Phosphorus (³¹P) MRSI provides opportunities to monitor potential biomarkers. However, current applications of ³¹P MRS are generally restricted to relatively small volumes as small coils are used. Conventional surface coils require high energy adiabatic RF pulses to achieve flip angle homogeneity, leading to high specific absorption rates (SARs), and occupy space within the MRI bore. A birdcage coil behind the bore cover can potentially reduce the SAR constraints massively by use of conventional amplitude modulated pulses without sacrificing patient space. Here, we demonstrate that the integrated ³¹P birdcage coil setup with a high power RF amplifier at 7 T allows for low flip angle excitations with short repetition time (T_R) for fast 3D chemical shift imaging (CSI) and 3D T₁‐weighted CSI as well as high flip angle multi‐refocusing pulses, enabling multi‐echo CSI that can measure metabolite T₂, over a large field of view in the body. B₁⁺ calibration showed a variation of only 30% in maximum B₁ in four volunteers. High signal‐to‐noise ratio (SNR) MRSI was obtained in the gluteal muscle using two fast in vivo 3D spectroscopic imaging protocols, with low and high flip angles, and with multi‐echo MRSI without exceeding SAR levels. In addition, full liver MRSI was achieved within SAR constraints. The integrated ³¹P body coil allowed for fast spectroscopic imaging and successful implementation of the multi‐echo method in the body at 7 T. Moreover, no additional enclosing hardware was needed for ³¹P excitation, paving the way to include larger subjects and more space for receiver arrays. The increase in possible number of RF excitations per scan time, due to the improved B₁⁺ homogeneity and low SAR, allows SNR to be exchanged for spatial resolution in CSI and/or T₁ weighting by simply manipulating T_R and/or flip angle to detect and quantify ratios from different molecular species.     

Estimating B1+ in the breast at 7 T using a generic template

Dynamic contrast‐enhanced MRI is the workhorse of breast MRI, where the diagnosis of lesions is largely based on the enhancement curve shape. However, this curve shape is biased by RF transmit (B₁⁺) field inhomogeneities. B₁⁺ field information is required in order to correct these. The use of a generic, coil‐specific B₁⁺ template is proposed and tested. Finite‐difference time‐domain simulations for B₁⁺ were performed for healthy female volunteers with a wide range of breast anatomies. A generic B₁⁺ template was constructed by averaging simulations based on four volunteers. Three‐dimensional B₁⁺ maps were acquired in 15 other volunteers. Root mean square error (RMSE) metrics were calculated between individual simulations and the template, and between individual measurements and the template. The agreement between the proposed template approach and a B₁⁺ mapping method was compared against the agreement between acquisition and reacquisition using the same mapping protocol. RMSE values (% of nominal flip angle) comparing individual simulations with the template were in the range 2.00‐4.01%, with mean 2.68%. RMSE values comparing individual measurements with the template were in the range8.1‐16%, with mean 11.7%. The agreement between the proposed template approach and a B₁⁺ mapping method was only slightly worse than the agreement between two consecutive acquisitions using the same mapping protocol in one volunteer: the range of agreement increased from ±16% of the nominal angle for repeated measurement to ±22% for the B₁⁺ template. With local RF transmit coils, intersubject differences in B₁⁺ fields of the breast are comparable to the accuracy of B₁⁺ mapping methods, even at 7 T. Consequently, a single generic B₁⁺ template suits subjects over a wide range of breast anatomies, eliminating the need for a time‐consuming B₁⁺ mapping protocol.     

Performance and safety assessment of an integrated transmit array for body imaging at 7 T under consideration of specific absorption rate,tissue temperature,and thermal dose

In this study, the performance of an integrated body-imaging array for 7 T with 32 radiofrequency (RF) channels under consideration of local specific absorption rate (SAR), tissue temperature, and thermal dose limits was evaluated and the imaging performance was compared with a clinical 3 T body coil. Thirty-two transmit elements were placed in three rings between the bore liner and RF shield of the gradient coil. Slice-selective RF pulse optimizations for B₁ shimming and spokes were performed for differently oriented slices in the body under consideration of realistic constraints for power and local SAR. To improve the B₁⁺ homogeneity, safety assessments based on temperature and thermal dose were performed to possibly allow for higher input power for the pulse optimization than permissible with SAR limits. The results showed that using two spokes, the 7 T array outperformed the 3 T birdcage in all the considered regions of interest. However, a significantly higher SAR or lower duty cycle at 7 T is necessary in some cases to achieve similar B₁⁺ homogeneity as at 3 T. The homogeneity in up to 50 cm-long coronal slices can particularly benefit from the high RF shim performance provided by the 32 RF channels. The thermal dose approach increases the allowable input power and the corresponding local SAR, in one example up to 100 W/kg, without limiting the exposure time necessary for an MR examination. In conclusion, the integrated antenna array at 7 T enables a clinical workflow for body imaging and comparable imaging performance to a conventional 3 T clinical body coil.     

Boosting the SNR by adding a receive‐only endorectal monopole to an external antenna array for high‐resolution,T2‐weighted imaging of early‐stage cervical cancer with 7‐T MRI

The aim of this study was to investigate the signal‐to‐noise ratio (SNR) gain in early‐stage cervical cancer at ultrahigh‐field MRI (e.g. 7 T) using a combination of multiple external antennas and a single endorectal antenna. In particular, we used an endorectal monopole antenna to increase the SNR in cervical magnetic resonance imaging (MRI). This should allow high‐resolution, T₂‐weighted imaging and magnetic resonance spectroscopy (MRS) for metabolic staging, which could facilitate the local tumor status assessment. In a prospective feasibility study, five healthy female volunteers and six patients with histologically proven stage IB1–IIB cervical cancer were scanned at 7 T. We used seven external fractionated dipole antennas for transmit–receive (transceive) and an endorectally placed monopole antenna for reception only. A region of interest, containing both normal cervix and tumor tissue, was selected for the SNR measurement. Separated signal and noise measurements were obtained in the region of the cervix for each element and in the near field of the monopole antenna (radius < 30 mm) to calculate the SNR gain of the endorectal antenna in each patient. We obtained high‐resolution, T₂‐weighted images with a voxel size of 0.7 × 0.8 × 3.0 mm³. In four cases with optimal placement of the endorectal antenna (verified on the T₂‐weighted images), a mean gain of 2.2 in SNR was obtained at the overall cervix and tumor tissue area. Within a radius of 30 mm from the monopole antenna, a mean SNR gain of 3.7 was achieved in the four optimal cases. Overlap between the two different regions of the SNR calculations was around 24%. We have demonstrated that the use of an endorectal monopole antenna substantially increases the SNR of 7‐T MRI at the cervical anatomy. Combined with the intrinsically high SNR of ultrahigh‐field MRI, this gain may be employed to obtain metabolic information using MRS and to enhance spatial resolutions to assess tumor invasion.     

Regulatory T‐cells in acute dengue viral infection

Although regulatory T‐cells (T_regs) have been shown to be expanded in acute dengue, their role in pathogenesis and their relationship to clinical disease severity and extent of viraemia have not been fully evaluated. The frequency of T_regs was assessed in 56 adult patients with acute dengue by determining the proportion of forkhead box protein 3 (FoxP3) expressing CD4⁺ CD25⁺T‐cells (FoxP3⁺ cells). Dengue virus (DENV) viral loads were measured by quantitative real‐time polymerase chain reaction (PCR) and DENV‐specific T‐cell responses were measured by ex‐vivo interferon (IFN)‐γ enzyme‐linked immunospot (ELISPOT) assays to overlapping peptide pools of DENV‐NS3, NS1 and NS5. CD45RA and CCR4 were used to phenotype different subsets of T‐cells and their suppressive potential was assessed by their expression of cytotoxic T lymphocyte‐antigen 4 (CTLA‐4) and Fas. While the frequency of FoxP3⁺ cells in patients was significantly higher (P < 0·0001) when compared to healthy individuals, they did not show any relationship with clinical disease severity or the degree of viraemia. The frequency of FoxP3⁺ cells did not correlate with either ex‐vivo IFN‐γ DENV‐NS3‐, NS5‐ or NS1‐specific T‐cell responses. FoxP3⁺ cells of patients with acute dengue were predominantly CD45RA⁺ FoxP3^low, followed by CD45RA‐FoxP3^low, with only a small proportion of FoxP3⁺ cells being of the highly suppressive effector Treg subtype. Expression of CCR4 was also low in the majority of T‐cells, with only CCR4 only being expressed at high levels in the effector T_reg population. Therefore, although FoxP3⁺ cells are expanded in acute dengue, they predominantly consist of naive T_regs, with poor suppressive capacity.     

Improved off‐resonance phase behavior using a phase‐inverted adiabatic half‐passage pulse for 13C MRS in humans at 7 T

In vivo ¹³C MRS at high field benefits from an improved SNR and spectral resolution especially when using surface coils in combination with adiabatic pulses, such as the adiabatic half‐passage (AHP) pulse for ¹³C excitation. However, the excitation profile of the AHP pulse is asymmetric relative to the carrier frequency, which could lead to asymmetric excitation of the spectral lines relative to the center of the spectrum. In this study, a pulse‐acquire sequence was designed for adiabatic ¹³C excitation with a symmetric bandwidth, utilizing a combination of two AHP pulses with inverted phases in alternate scans. Magnetization and phase behavior as a function of frequency offset and RF amplitude of the B₁ field, as well as the steady‐state transverse magnetization response to off‐resonance, were simulated. Excitation properties of the combined pulse sequence were studied by ²³Na imaging and ¹³C spectroscopy in vitro on a phantom and in vivo on the human calf at 7 T. Simulations demonstrated symmetric transverse magnetization and phase with respect to positive and negative frequency offsets when using two AHP pulses with inverted phases in alternate scans, thereby minimizing baseline distortion and achieving symmetric T₁ weighting, as confirmed by in vitro measurements. The intensities of the lipid peaks at 15, 30, 62, 73, and 130 ppm were in agreement with those theoretically predicted using two AHP pulses with inverted phases in alternate scans. We conclude that using two phase‐inverted AHP pulses improves the symmetry of the ¹³C excitation profile and phase response to off‐resonance effects at 7 T in comparison with using a single AHP pulse.     

CMV drives the expansion of highly functional memory T cells expressing NK‐cell receptors in renal transplant recipients

Cytomegalovirus (CMV) is a common opportunistic infection encountered in renal transplant recipients (RTRs) and may be reactivated without symptoms at any time post‐transplant. We describe how active and latent CMV affect T‐cell subsets in RTRs who are stable on maintenance therapy. T‐cell responses to CMV were assessed in RTRs (n = 54) >2 years post‐transplant, and healthy controls (n = 38). Seven RTRs had CMV DNA detectable in plasma. CMV antibody and DNA aligned with increased proportions of CD8⁺ T cells and reduced CD4/CD8 ratios. This paralleled an expansion of effector memory T‐cell (T_EM), terminally differentiated T‐cell (T_EMRA) and CD57⁺ T_EMRA cell populations. Expression of NK‐cell receptors, LIR‐1 and KLRG1 on CD4⁺ and CD8⁺ CD57⁺ T_EM and T_EMRA cells correlated with elevated interferon‐γ and cytotoxic responses to anti‐CD3 and increased cytotoxic responses to CMV phosphoprotein (pp) 65 in RTRs who carried CMV DNA. CD8⁺ T cells from all CMV seropositive RTRs responded efficiently to CMV immediate early (IE) ‐1 peptides. The data show that latent and active CMV infection can alter T‐cell subsets in RTRs many years after transplantation, and up‐regulate T‐cell expression of NK‐cell receptors. This may enhance effector responses of CD4⁺ and CD8⁺ T cells against CMV.     

Measuring renal tissue relaxation times at 7 T

As developments in RF coils and RF management strategies make performing ultra‐high‐field renal imaging feasible, understanding the relaxation times of the tissue becomes increasingly important for tissue characterization, sequence optimization and quantitative functional renal imaging, such as renal perfusion imaging using arterial spin labeling. By using a magnetization‐prepared single‐breath‐hold fast spin echo imaging method, human renal T₁ and T₂ imaging studies were successfully performed at 7 T with 11 healthy volunteers (eight males, 45 ± 17 years, and three females, 29 ± 7 years, mean ± standard deviation, S.D.) while addressing challenges of B₁⁺ inhomogeneity and short‐term specific absorption rate limits. At 7 T, measured renal T₁ values for the renal cortex and medulla (mean ± S.D.) from five healthy volunteers who participated in both 3 T and two‐session 7 T studies were 1661 ± 68 ms and 2094 ± 67 ms, and T₂ values were 108 ± 7 ms and 126 ± 6 ms. For comparison, similar measurements were made at 3 T, where renal cortex and medulla T₁ values of 1261 ± 86 ms and 1676 ± 94 ms and T₂ values of 121 ± 5 ms and 138 ± 7 ms were obtained. Measurements at 3 T and 7 T were significantly different for both T₁ and T₂ values in both renal tissues. Reproducibility studies at 7 T demonstrated that T₁ and T₂ estimations were robust, with group mean percentage differences of less than 4%. Copyright © 2014 John Wiley & Sons, Ltd.     

Wideband Self‐Grounded Bow‐Tie Antenna for Thermal MR

The objective of this study was the design, implementation, evaluation and application of a compact wideband self‐grounded bow‐tie (SGBT) radiofrequency (RF) antenna building block that supports anatomical proton (¹H) MRI, fluorine (¹⁹F) MRI, MR thermometry and broadband thermal intervention integrated in a whole‐body 7.0 T system. Design considerations and optimizations were conducted with numerical electromagnetic field (EMF) simulations to facilitate a broadband thermal intervention frequency of the RF antenna building block. RF transmission (B₁⁺) field efficiency and specific absorption rate (SAR) were obtained in a phantom, and the thigh of human voxel models (Ella, Duke) for ¹H and ¹⁹F MRI at 7.0 T. B₁⁺ efficiency simulations were validated with actual flip‐angle imaging measurements. The feasibility of thermal intervention was examined by temperature simulations (f = 300, 400 and 500 MHz) in a phantom. The RF heating intervention (P_in = 100 W, t = 120 seconds) was validated experimentally using the proton resonance shift method and fiberoptic probes for temperature monitoring. The applicability of the SGBT RF antenna building block for in vivo ¹H and ¹⁹F MRI was demonstrated for the thigh and forearm of a healthy volunteer. The SGBT RF antenna building block facilitated ¹⁹F and ¹H MRI at 7.0 T as well as broadband thermal intervention (234‐561 MHz). For the thigh of the human voxel models, a B₁⁺ efficiency ≥11.8 μT/√kW was achieved at a depth of 50 mm. Temperature simulations and heating experiments in a phantom demonstrated a temperature increase ΔT >7 K at a depth of 10 mm. The compact SGBT antenna building block provides technology for the design of integrated high‐density RF applicators and for the study of the role of temperature in (patho‐) physiological processes by adding a thermal intervention dimension to an MRI device (Thermal MR).     

Differential CD4+ T‐cell responses of allergic and non‐allergic subjects to the immunodominant epitope region of the horse major allergen Equ c 1

The responses of allergen‐specific CD4⁺ T cells of allergic and healthy individuals are still incompletely understood. Our objective was to investigate the functional and phenotypic properties of CD4⁺ T cells of horse‐allergic and healthy subjects specific to the immunodominant epitope region of the major horse allergen Equ c 1. Specific T‐cell lines (TCLs) and clones were generated from peripheral blood mononuclear cells with Equ c 1_143–160, the peptide containing the immunodominant epitope region of Equ c 1. The frequency, proliferative response, cytokine production and HLA restriction of the cells were examined. The frequency of Equ c 1‐specific CD4⁺ T cells was low (approximately 1 per 10⁶ CD4⁺ T cells) in both allergic and non‐allergic subjects. The cells of allergic subjects had a stronger proliferative capacity than those of non‐allergic subjects, and they predominantly emerged from the memory T‐cell pool and expressed the T helper type 2 cytokine profile, whereas the cells of non‐allergic subjects emerged from the naive T‐cell pool and produced low levels of interferon‐γ and interleukin‐10. T‐cell response to Equ c 1_143–160 was restricted by several common HLA class II molecules from both DQ and DR loci. As the phenotypic and functional properties of Equ c 1‐specific CD4⁺ T cells differ between allergic and non‐allergic subjects, allergen‐specific T cells appear to be tightly implicated in the development of diseased or healthy outcome. Restriction of the specific CD4⁺ T‐cell response by multiple HLA alleles suggests that Equ c 1_143–160 is a promising candidate for peptide‐based immunotherapy.     

Ventricular B1+ perturbation at 7 T – real effect or measurement artifact?

The objective of this work was to explore the origin of local B₁⁺ perturbations in the ventricles measured at 7 T. The B₁⁺ field in the human brain was mapped using four different MRI techniques: dual refocusing echo acquisition mode (DREAM), actual flip‐angle imaging (AFI), saturated double‐angle method (SDAM) and Bloch–Siegert shift (BSS). Electromagnetic field simulations of B₁⁺ were performed in male and female subject models to assess the dependence of the B₁⁺ distribution on the dielectric properties of cerebrospinal fluid and subject anatomy. All four B₁⁺ mapping techniques, based on different B₁⁺ encoding mechanisms, show ‘residual’ structure of the ventricles, with a slightly enhanced B₁⁺ field in the ventricles. Electromagnetic field simulations indicate that this effect is real and arises from the strong contrast in electrical conductivity between cerebrospinal fluid and brain tissue. The simulated results were in good agreement with those obtained in three volunteers. Measured local B₁⁺ perturbations in the ventricles at 7 T can be partially explained by the high contrast in electrical conductivity between cerebrospinal fluid and white matter, in addition to effects related to the particular B₁⁺ measurement technique used. Copyright © 2014 John Wiley & Sons, Ltd.     

Triple‐echo steady‐state T2 relaxometry of the human brain at high to ultra‐high fields

Quantitative MRI techniques, such as T₂ relaxometry, have demonstrated the potential to detect changes in the tissue microstructure of the human brain with higher specificity to the underlying pathology than in conventional morphological imaging. At high to ultra‐high field strengths, quantitative MR‐based tissue characterization benefits from the higher signal‐to‐noise ratio traded for either improved resolution or reduced scan time, but is impaired by severe static (B₀) and transmit (B₁) field heterogeneities. The objective of this study was to derive a robust relaxometry technique for fast T₂ mapping of the human brain at high to ultra‐high fields, which is highly insensitive to B₀ and B₁ field variations. The proposed method relies on a recently presented three‐dimensional (3D) triple‐echo steady‐state (TESS) imaging approach that has proven to be suitable for fast intrinsically B₁‐insensitive T₂ relaxometry of rigid targets. In this work, 3D TESS imaging is adapted for rapid high‐ to ultra‐high‐field two‐dimensional (2D) acquisitions. The achieved short scan times of 2D TESS measurements reduce motion sensitivity and make TESS‐based T₂ quantification feasible in the brain. After validation in vitro and in vivo at 3 T, T₂ maps of the human brain were obtained at 7 and 9.4 T. Excellent agreement between TESS‐based T₂ measurements and reference single‐echo spin‐echo data was found in vitro and in vivo at 3 T, and T₂ relaxometry based on TESS imaging was proven to be feasible and reliable in the human brain at 7 and 9.4 T. Although prominent B₀ and B₁ field variations occur at ultra‐high fields, the T₂ maps obtained show no B₀‐ or B₁‐related degradations. In conclusion, as a result of the observed robustness, TESS T₂ may emerge as a valuable measure for the early diagnosis and progression monitoring of brain diseases in high‐resolution 2D acquisitions at high to ultra‐high fields. Copyright © 2014 John Wiley & Sons, Ltd.     

Programmed death (PD)‐1 molecule and its ligand PD‐L1 distribution among memory CD4 and CD8 T cell subsets in human immunodeficiency virus‐1‐infected individuals

Human immunodeficiency virus (HIV)‐1 causes T cell anergy and affects T cell maturation. Various mechanisms are responsible for impaired anti‐HIV‐1‐specific responses: programmed death (PD)‐1 molecule and its ligand PD‐L1 are negative regulators of T cell activity and their expression is increased during HIV‐1 infection. This study examines correlations between T cell maturation, expression of PD‐1 and PD‐L1, and the effects of their blockade. Peripheral blood mononuclear cells (PBMC) from 24 HIV‐1⁺ and 17 uninfected individuals were phenotyped for PD‐1 and PD‐L1 expression on CD4⁺ and CD8⁺ T cell subsets. The effect of PD‐1 and PD‐L1 blockade on proliferation and interferon (IFN)‐γ production was tested on eight HIV‐1⁺ patients. Naive (CCR7⁺CD45RA⁺) CD8⁺ T cells were reduced in HIV‐1 aviraemic (P = 0·0065) and viraemic patients (P = 0·0130); CD8 T effector memory subsets [CCR7^‐CD45RA^–(T_EM)] were increased in HIV‐1⁺ aviraemic (P = 0·0122) and viraemic (P = 0·0023) individuals versus controls. PD‐1 expression was increased in CD4 naive (P = 0·0496), central memory [CCR7⁺CD45RA^– (T_CM); P = 0·0116], T_EM (P = 0·0037) and CD8 naive T cells (P = 0·0133) of aviraemic HIV‐1⁺versus controls. PD‐L1 was increased in CD4 T_EMRA (CCR7^‐CD45RA⁺, P = 0·0119), CD8 T_EM (P = 0·0494) and CD8 T_EMRA (P = 0·0282) of aviraemic HIV‐1⁺versus controls. PD‐1 blockade increased HIV‐1‐specific proliferative responses in one of eight patients, whereas PD‐L1 blockade restored responses in four of eight patients, but did not increase IFN‐γ‐production. Alteration of T cell subsets, accompanied by increased PD‐1 and PD‐L1 expression in HIV‐1 infection contributes to anergy and impaired anti‐HIV‐1‐specific responses which are not rescued when PD‐1 is blocked, in contrast to when PD‐L1 is blocked, due possibly to an ability to bind to receptors other than PD‐1.     

On‐resonance and off‐resonance continuous wave constant amplitude spin‐lock and T1ρ quantification in the presence of B1 and B0 inhomogeneities

Spin‐lock MRI is a valuable diagnostic imaging technology, as it can be used to probe the macromolecule environment of tissues. Quantitative T_1ρ imaging is one application of spin‐lock MRI that is reported to be promising for a number of clinical applications. Spin‐lock is often performed with a continuous RF wave at a constant RF amplitude either on resonance or off resonance. However, both on‐ and off‐resonance spin‐lock approaches are susceptible to B₁ and B₀ inhomogeneities, which results in image artifacts and quantification errors. In this work, we report a continuous wave constant amplitude spin‐lock approach that can achieve negligible image artifacts in the presence of B₁ and B₀ inhomogeneities for both on‐ and off‐resonance spin‐lock. Under the adiabatic condition, by setting the maximum B₁ amplitude of the adiabatic pulses equal to the B₁ amplitude of spin‐lock RF pulse, the spins are ensured to align along the effective field throughout the spin‐lock process. We show that this results in simultaneous compensation of B₁ and B₀ inhomogeneities for both on‐ and off‐resonance spin‐lock. The relaxation effect during the entire adiabatic half passage (AHP) and reverse AHP, and the stationary solution of the Bloch‐McConnell equation present at off‐resonance frequency offset, are considered in the revised relaxation model. We demonstrate that these factors create a direct current component to the conventional relaxation model. In contrast to the previously reported dual‐acquisition method, the revised relaxation model just requires one acquisition to perform quantification. The simulation, phantom, and in vivo experiments demonstrate that the proposed approach achieves superior image quality compared with the existing methods, and the revised relaxation model can perform T_1ρ quantification with one acquisition instead of two.     

Slice‐selective FID acquisition,localized by outer volume suppression (FIDLOVS) for 1H‐MRSI of the human brain at 7 T with minimal signal loss

In comparison to 1.5 and 3 T, MR spectroscopic imaging at 7 T benefits from signal‐to‐noise ratio (SNR) gain and increased spectral resolution and should enable mapping of a large number of metabolites at high spatial resolutions. However, to take full advantage of the ultra‐high field strength, severe technical challenges, e.g. related to very short T₂ relaxation times and strict limitations on the maximum achievable B₁ field strength, have to be resolved. The latter results in a considerable decrease in bandwidth for conventional amplitude modulated radio frequency pulses (RF‐pulses) and thus to an undesirably large chemical‐shift displacement artefact. Frequency‐modulated RF‐pulses can overcome this problem; but to achieve a sufficient bandwidth, long pulse durations are required that lead to undesirably long echo‐times in the presence of short T₂ relaxation times. In this work, a new magnetic resonance spectroscopic imaging (MRSI) localization scheme (free induction decay acquisition localized by outer volume suppression, FIDLOVS) is introduced that enables MRSI data acquisition with minimal SNR loss due to T₂ relaxation and thus for the first time mapping of an extended neurochemical profile in the human brain at 7 T. To overcome the contradictory problems of short T₂ relaxation times and long pulse durations, the free induction decay (FID) is directly acquired after slice‐selective excitation. Localization in the second and third dimension and skull lipid suppression are based on a T₁‐ and B₁‐insensitive outer volume suppression (OVS) sequence. Broadband frequency‐modulated excitation and saturation pulses enable a minimization of the chemical‐shift displacement artefact in the presence of strict limits on the maximum B₁ field strength. The variable power RF pulses with optimized relaxation delays (VAPOR) water suppression scheme, which is interleaved with OVS pulses, eliminates modulation side bands and strong baseline distortions. Third order shimming is based on the accelerated projection‐based automatic shimming routine (FASTERMAP) algorithm. The striking SNR and spectral resolution enable unambiguous quantification and mapping of 12 metabolites including glutamate (Glu), glutamine (Gln), N‐acetyl‐aspartatyl‐glutamate (NAAG), γ‐aminobutyric acid (GABA) and glutathione (GSH). The high SNR is also the basis for highly spatially resolved metabolite mapping. Copyright © 2009 John Wiley & Sons, Ltd.     

Whole‐body radiofrequency coil for 31P MRSI at 7 T

Widespread use of ultrahigh‐field ³¹P MRSI in clinical studies is hindered by the limited field of view and non‐uniform radiofrequency (RF) field obtained from surface transceivers. The non‐uniform RF field necessitates the use of high specific absorption rate (SAR)‐demanding adiabatic RF pulses, limiting the signal‐to‐noise ratio (SNR) per unit of time. Here, we demonstrate the feasibility of using a body‐sized volume RF coil at 7 T, which enables uniform excitation and ultrafast power calibration by pick‐up probes. The performance of the body coil is examined by bench tests, and phantom and in vivo measurements in a 7‐T MRI scanner. The accuracy of power calibration with pick‐up probes is analyzed at a clinical 3‐T MR system with a close to identical ¹H body coil integrated at the MR system. Finally, we demonstrate high‐quality three‐dimensional ³¹P MRSI of the human body at 7 T within 5 min of data acquisition that includes RF power calibration. Copyright © 2016 John Wiley & Sons, Ltd.     

Characteristics of Schistosoma japonicum infection induced IFN‐γ and IL‐4 co‐expressing plasticity Th cells

Schistosoma japonicum infection can induce granulomatous inflammation and cause tissue damage in the mouse liver. The cytokine secretion profile of T helper (Th) cells depends on both the nature of the activating stimulus and the local microenvironment (e.g. cytokines and other soluble factors). In the present study, we found an accumulation of large numbers of IFN‐γ⁺ IL‐4⁺ CD4⁺ T cells in mouse livers. This IFN‐γ⁺ IL‐4⁺ cell population increased from 0·68 ± 0·57% in uninfected mice to 7·05 ± 3·0% by week 4 following infection and to 9·6 ± 5·28% by week 6, before decreasing to 6·3 ± 5·9% by week 8 in CD4 T cells. Moreover, IFN‐γ⁺ IL‐4⁺ Th cells were also found in mouse spleen and mesenteric lymph nodes 6 weeks after infection. The majority of the IFN‐γ⁺ IL‐4⁺ Th cells were thought to be related to a state of immune activation, and some were memory T cells. Moreover, we found that these S. japonicum infection‐induced IFN‐γ⁺ IL‐4⁺ cells could express interleukin‐2 (IL‐2), IL‐9, IL‐17 and high IL‐10 levels at 6 weeks after S. japonicum infection. Taken together, our data suggest the existence of a population of IFN‐γ⁺ IL‐4⁺ plasticity effector/memory Th cells following S. japonicum infection in C57BL/6 mice.