Chromatin restriction by the nucleosome remodeler Mi-2ß and functional interplay with lineage-specific transcription regulators control B-cell differentiation.

Coordinated induction, but also repression, of genes are key to normal differentiation. Although the role of lineage-specific transcription regulators has been studied extensively, their functional integration with chromatin remodelers, one of the key enzymatic machineries that control chromatin accessibility, remains ill-defined. Here we investigate the role of Mi-2ß, a SNF-2-like nucleosome remodeler and key component of the nucleosome remodeling and histone deacetylase (NuRD) complex in early B cells. Inactivation of Mi-2ß arrested differentiation at the large pre-B-cell stage and caused derepression of cell adhesion and cell migration signaling factors by increasing chromatin access at poised enhancers and chromosome architectural elements. Mi-2ß also supported IL-7R signaling, survival, and proliferation by repressing negative effectors of this pathway. Importantly, overexpression of Bcl2, a mitochondrial prosurvival gene and target of IL-7R signaling, partly rescued the differentiation block caused by Mi-2ß loss. Mi-2ß stably associated with chromatin sites that harbor binding motifs for IKAROS and EBF1 and physically associated with these transcription factors both on and off chromatin. Notably, Mi-2ß shared loss-of-function cellular and molecular phenotypes with IKAROS and EBF1, albeit in a distinct fashion. Thus, the nucleosome remodeler Mi-2ß promotes pre-B-cell differentiation by providing repression capabilities to distinct lineage-specific transcription factor-based regulatory networks.

Formyl peptide receptor 2 and heart disease.

Formyl peptide receptor type 2 (FPR2) regulates the initiation and resolution phases of the inflammatory response. In the setting of heart injury and disease, dysregulated inflammation can potentiate maladaptive healing and pathological remodeling of the heart leading to cardiac dysfunction and failure. The potential to regulate and resolve adverse inflammation is postulated to improve outcome in the setting of heart disease. This review covers emerging concepts on the role of FPR2 in heart disease and strategies to activate pro-resolution processes to limit disease progression. We summarize key preclinical studies that support use of FPR2 agonists in heart disease. Finally, we briefly discuss the status of FPR2 agonists under evaluation in the clinic.

BCAS2 regulates oocyte meiotic prophase I by participating in mRNA alternative splicing.

Oocyte meiotic prophase I (MI) is an important event in female reproduction. Breast cancer amplified sequence 2 (BCAS2) is a component of the spliceosome. Previous reports have shown that BCAS2 is critical in male germ cell meiosis, oocyte development, and early embryo genome integrity. However, the role of BCAS2 in oocyte meiosis has not been reported. We used Stra8-GFPCre mice to knock out Bcas2 in oocytes during the pachytene phase. The results of fertility tests showed that Bcas2 conditional knockout (cKO) in oocytes results in infertility in female mice. Morphological analysis showed that the number of primordial follicles in the ovaries of 2-month-old (M) mice was significantly reduced and that follicle development was blocked. Further analysis showed that the number of primordial follicles decreased and that follicle development was slowed in 7-day postpartum (dpp) ovaries. Moreover, primordial follicles undergo apoptosis, and DNA damage cannot be repaired in primary follicle oocytes. Meiosis was abnormal; some oocytes could not reach the diplotene stage, and more oocytes could not develop to the dictyotene stage. Alternative splicing (AS) analysis revealed abnormal AS of deleted in azoospermia like (Dazl) and diaphanous related formin 2 (Diaph2) oogenesis-related genes in cKO mouse ovaries, and the process of AS was involved by CDC5L and PRP19.

A Multivariate analysis on evoked components of Chinese semantic congruity: an OP-MEG study with EEG.

The application of wearable magnetoencephalography using optically-pumped magnetometers has drawn extensive attention in the field of neuroscience. Electroencephalogram system can cover the whole head and reflect the overall activity of a large number of neurons. The efficacy of optically-pumped magnetometer in detecting event-related components can be validated through electroencephalogram results. Multivariate pattern analysis is capable of tracking the evolution of neurocognitive processes over time. In this paper, we adopted a classical Chinese semantic congruity paradigm and separately collected electroencephalogram and optically-pumped magnetometer signals. Then, we verified the consistency of optically-pumped magnetometer and electroencephalogram in detecting N400 using mutual information index. Multivariate pattern analysis revealed the difference in decoding performance of these two modalities, which can be further validated by dynamic/stable coding analysis on the temporal generalization matrix. The results from searchlight analysis provided a neural basis for this dissimilarity at the magnetoencephalography source level and the electroencephalogram sensor level. This study opens a new avenue for investigating the brain's coding patterns using wearable magnetoencephalography and reveals the differences in sensitivity between the two modalities in reflecting neuron representation patterns.

The novel antibody fusion protein rhNRG1-HER3i promotes heart regeneration by enhancing NRG1-ERBB4 signaling pathway.

Stimulating cardiomyocyte proliferation in the adult heart has emerged as a promising strategy for cardiac regeneration following myocardial infarction (MI). The NRG1-ERBB4 signaling pathway has been implicated in the regulation of cardiomyocyte proliferation. However, the therapeutic potential of recombinant human NRG1 (rhNRG1) has been limited due to the low expression of ERBB4 in adult cardiomyocytes. Here, we investigated whether a fusion protein of rhNRG1 and an ERBB3 inhibitor (rhNRG1-HER3i) could enhance the affinity of NRG1 for ERBB4 and promote adult cardiomyocyte proliferation. In vitro and in vivo experiments were conducted using postnatal day 1 (P1), P7, and adult cardiomyocytes. Western blot analysis was performed to assess the expression and activity of ERBB4. Cardiomyocyte proliferation was evaluated using Ki67 and pH 3 immunostaining, while fibrosis was assessed using Masson staining. Our results indicate that rhNRG1-HER3i, but not rhNRG1, promoted P7 and adult cardiomyocyte proliferation. Furthermore, rhNRG1-HER3i improved cardiac function and reduced cardiac fibrosis in post-MI hearts. Administration of rhNRG1-HER3i inhibited ERBB3 phosphorylation while increasing ERBB4 phosphorylation in adult mouse hearts. Additionally, rhNRG1-HER3i enhanced angiogenesis following MI compared to rhNRG1. In conclusion, our findings suggest that rhNRG1-HER3i is a viable therapeutic approach for promoting adult cardiomyocyte proliferation and treating MI by enhancing NRG1-ERBB4 signaling pathway.

Ideal adaptive control in biological systems: an analysis of P -invariance and dynamical compensation properties.

BACKGROUND: Dynamical compensation (DC) provides robustness to parameter fluctuations. As an example, DC enables control of the functional mass of endocrine or neuronal tissue essential for controlling blood glucose by insulin through a nonlinear feedback loop. Researchers have shown that DC is related to the structural unidentifiability and the P -invariance property. The P -invariance property is a sufficient and necessary condition for the DC property. DC has been seen in systems with at least three dimensions. In this article, we discuss DC and P -invariance from an adaptive control perspective. An adaptive controller automatically adjusts its parameters to optimise performance, maintain stability, and deal with uncertainties in a system. RESULTS: We initiate our analysis by introducing a simplified two-dimensional dynamical model with DC, fostering experimentation and understanding of the system's behavior. We explore the system's behavior with time-varying input and disturbance signals, with a focus on illustrating the system's P -invariance properties in phase portraits and step-like response graphs. CONCLUSIONS: We show that DC can be seen as a case of ideal adaptive control since the system is invariant to the compensated parameter.

Microbe-disease associations prediction by graph regularized non-negative matrix factorization with L 2 , 1 $$ {L}_{2,1} $$ norm regularization terms.

Microbes are involved in a wide range of biological processes and are closely associated with disease. Inferring potential disease-associated microbes as the biomarkers or drug targets may help prevent, diagnose and treat complex human diseases. However, biological experiments are time-consuming and expensive. In this study, we introduced a new method called iPALM-GLMF, which modelled microbe-disease association prediction as a problem of non-negative matrix factorization with graph dual regularization terms and L 2 , 1 $$ {L}_{2,1} $$ norm regularization terms. The graph dual regularization terms were used to capture potential features in the microbe and disease space, and the L 2 , 1 $$ {L}_{2,1} $$ norm regularization terms were used to ensure the sparsity of the feature matrices obtained from the non-negative matrix factorization and to improve the interpretability. To solve the model, iPALM-GLMF used a non-negative double singular value decomposition to initialize the matrix factorization and adopted an inertial Proximal Alternating Linear Minimization iterative process to obtain the final matrix factorization results. As a result, iPALM-GLMF performed better than other existing methods in leave-one-out cross-validation and fivefold cross-validation. In addition, case studies of different diseases demonstrated that iPALM-GLMF could effectively predict potential microbial-disease associations. iPALM-GLMF is publicly available at https://github.com/LiangzheZhang/iPALM-GLMF.

Myoglobin deficiency impairs maximal oxygen uptake and exercise performance: a lesson from Mb-/- mice.

Myoglobin (Mb) plays an important role at rest and during exercise as a reservoir of oxygen and has been suggested to regulate NO• bioavailability under hypoxic/acidic conditions. However, its ultimate role during exercise is still a subject of debate. We aimed to study the effect of Mb deficiency on maximal oxygen uptake ( V ̇ O 2 max ${\dot V_{{{\mathrm{O}}_2}\max }}$ ) and exercise performance in myoglobin knockout mice (Mb-/- ) when compared to control mice (Mb+/+ ). Furthermore, we also studied NO• bioavailability, assessed as nitrite (NO2 - ) and nitrate (NO3 - ) in the heart, locomotory muscle and in plasma, at rest and during exercise at exhaustion both in Mb-/- and in Mb+/+ mice. The mice performed maximal running incremental exercise on a treadmill with whole-body gas exchange measurements. The Mb-/- mice had lower body mass, heart and hind limb muscle mass (P < 0.001). Mb-/- mice had significantly reduced maximal running performance (P < 0.001). V ̇ O 2 max ${\dot V_{{{\mathrm{O}}_2}\max }}$ expressed in ml min-1 in Mb-/ - mice was 37% lower than in Mb+/+ mice (P < 0.001) and 13% lower when expressed in ml min-1  kg body mass-1 (P = 0.001). Additionally, Mb-/- mice had significantly lower plasma, heart and locomotory muscle NO2 - levels at rest. During exercise NO2 - increased significantly in the heart and locomotory muscles of Mb-/- and Mb+/+ mice, whereas no significant changes in NO2 - were found in plasma. Our study showed that, contrary to recent suggestions, Mb deficiency significantly impairs V ̇ O 2 max ${\dot V_{{{\mathrm{O}}_2}\max }}$ and maximal running performance in mice. KEY POINTS: Myoglobin knockout mice (Mb-/- ) possess lower maximal oxygen uptake ( V ̇ O 2 max ${\dot V_{{{\mathrm{O}}_2}\max }}$ ) and poorer maximal running performance than control mice (Mb+/+ ). Respiratory exchange ratio values at high running velocities in Mb-/- mice are higher than in control mice suggesting a shift in substrate utilization towards glucose metabolism in Mb-/- mice at the same running velocities. Lack of myoglobin lowers basal systemic and muscle NO• bioavailability, but does not affect exercise-induced NO2 - changes in plasma, heart and locomotory muscles. The present study demonstrates that myoglobin is of vital importance for V ̇ O 2 max ${\dot V_{{{\mathrm{O}}_2}\max }}$ and maximal running performance as well as explains why previous studies have failed to prove such a role of myoglobin when using the Mb-/- mouse model.

OsMADS5 interacts with OsSPL14/17 to inhibit rice root elongation by restricting cell proliferation of root meristem under ammonium supply.

Nitrogen (N) is a vital major nutrient for rice (Oryza sativa). Rice responds to different applications of N by altering its root morphology, including root elongation. Although ammonium ( NH 4 + ) is the primary source of N for rice, NH 4 + is toxic to rice roots and inhibits root elongation. However, the precise molecular mechanism that NH 4 + -inhibited root elongation of rice is not well understood. Here, we identified a rice T-DNA insert mutant of OsMADS5 with a longer seminal root (SR) under sufficient N conditions. Reverse-transcription quantitative PCR analysis revealed that the expression level of OsMADS5 was increased under NH 4 + compared with NO 3 - supply. Under NH 4 + conditions, knocking out OsMADS5 (cas9) produced a longer SR, phenocopying osmads5, while there was no significant difference in SR length between wild-type and cas9 under NO 3 - supply. Moreover, OsMADS5-overexpression plants displayed the opposite SR phenotype. Further study demonstrated that enhancement of OsMADS5 by NH 4 + supply inhibited rice SR elongation, likely by reducing root meristem activity of root tip, with the involvement of OsCYCB1;1. We also found that OsMADS5 interacted with OsSPL14 and OsSPL17 (OsSPL14/17) to repress their transcriptional activation by attenuating DNA binding ability. Moreover, loss of OsSPL14/17 function in osmads5 eliminated its stimulative effect on SR elongation under NH 4 + conditions, implying OsSPL14/17 may function downstream of OsMADS5 to mediate rice SR elongation under NH 4 + supply. Overall, our results indicate the existence of a novel modulatory pathway in which enhancement of OsMADS5 by NH 4 + supply represses the transcriptional activities of OsSPL14/17 to restrict SR elongation of rice.

Enhancing motor imagery in the third-person perspective by manipulating sense of body ownership with virtual reality.

Virtual reality (VR)-guided motor imagery (MI) is a widely used approach for motor rehabilitation, especially for patients with severe motor impairments. Most approaches provide visual guidance from the first-person perspective (1PP). MI training with visual guidance from the third-person perspective (3PP) remains largely unexplored. We argue that 3PP MI training has its own advantages and can supplement 1PP MI. For some movements beyond the view of 1PP, such as shoulder shrugging and other axial movements, MI are suitable performed under 3PP. However, the efficiency of existing paradigms for 3PP MI is unsatisfactory. We speculate that the absence of sense of body ownership (SOO) from 3PP could be one possible factor and hypothesize that 3PP MI could be enhanced by eliciting SOO over a 3PP avatar. Based on our hypothesis, a novel paradigm was proposed to enhance 3PP MI by inducing full-body illusion (FBI) from 3PP, which is similar to the so-called out-of-body experience (OBE), using synchronous visuo-tactile stimulus with VR. The event-related Electroencephalograph (EEG) desynchronization (ERD) at motor-related regions from 31 healthy participants were calculated and compared with a control paradigm without "OBE" FBI induction. This study attempts to enhance 3PP MI with FBI induction. It offers an opportunity to perform MI guided by action observation from 3PP with elicited SOO to the observed avatar. We believe that 3PP MI could provide more possibilities for effective rehabilitation training, when SOO could be elicited to a virtual avatar and the present work demonstrates its viability and effectiveness.

Synergistic effects of the KDM4C inhibitor SD70 and the menin inhibitor MI-503 against MLL::AF9-driven acute myeloid leukaemia.

MLL-rearranged (MLL-r) leukaemia is observed in approximately 10% of acute myeloid leukaemia (AML) and is associated with a relatively poor prognosis, highlighting the need for new treatment regimens. MLL fusion proteins produced by MLL rearrangements recruit KDM4C to mediate epigenetic reprogramming, which is required for the maintenance of MLL-r leukaemia. In this study, we used a combinatorial drug screen to selectively identify synergistic treatment partners for the KDM4C inhibitor SD70. The results showed that the drug combination of SD70 and MI-503, a potent menin-MLL inhibitor, induced synergistically enhanced apoptosis in MLL::AF9 leukaemia cells without affecting normal CD34+ cells. In vivo treatment with SD70 and MI-503 significantly prolonged survival in AML xenograft models. Differential gene expression analysis by RNA-seq following combined pharmacological inhibition of SD70 and MI-503 revealed changes in numerous genes, with MYC target genes being the most significantly downregulated. Taken together, these data provide preclinical evidence that the combination of SD70 and MI-503 is a potential dual-targeted therapy for MLL::AF9 AML.

B 1 + inhomogeneity mitigation for diffusion weighted MRI at 7T using TR-FOCI pulses.

PURPOSE: The purpose of this study is to improve the image quality of diffusion-weighted images obtained with a single RF transmit channel 7 T MRI setup using time-resampled frequency-offset corrected inversion (TR-FOCI) pulses to refocus the spins in a twice-refocused spin-echo readout scheme. METHODS: We replaced the conventional Shinnar-Le Roux-pulses in the twice refocused diffusion sequence with TR-FOCI pulses. The slice profiles were evaluated in simulation and experimentally in phantoms. The image quality was evaluated in vivo comparing the Shinnar-Le Roux and TR-FOCI implementation using a b value of 0 and of 1000 s/mm2. RESULTS: The b0 and diffusion-weighted images acquired using the modified sequence improved the image quality across the whole brain. A region of interest-based analysis showed an SNR increase of 113% and 66% for the nondiffusion-weighted (b0) and the diffusion-weighted (b = 1000 s/mm2) images in the temporal lobes, respectively. Investigation of all slices showed that the adiabatic pulses mitigated B 1 + $$ {B}_1^{+} $$ inhomogeneity globally using a conventional single-channel transmission setup. CONCLUSION: The TR-FOCI pulse can be used in a twice-refocused spin-echo diffusion pulse sequence to mitigate the impact of B 1 + $$ {B}_1^{+} $$ inhomogeneity on the signal intensity across the brain at 7 T. However, further work is needed to address SAR limitations.

The effect of and correction for through-slice dephasing on 2D gradient-echo double angle B 1 + mapping.

PURPOSE: To show that B 0 $$ {\mathrm{B}}_0 $$ variations through slice and slice profile effects are two major confounders affecting 2D dual angle B 1 + $$ {\mathrm{B}}_1^{+} $$ maps using gradient-echo signals and thus need to be corrected to obtain accurate B 1 + $$ {\mathrm{B}}_1^{+} $$ maps. METHODS: The 2D gradient-echo transverse complex signal was Bloch-simulated and integrated across the slice dimension including nonlinear variations in B 0 $$ {\mathrm{B}}_0 $$ inhomogeneities through slice. A nonlinear least squares fit was used to find the B 1 + $$ {\mathrm{B}}_1^{+} $$ factor corresponding to the best match between the two gradient-echo signals experimental ratio and the Bloch-simulated ratio. The correction was validated in phantom and in vivo at 3T. RESULTS: For our RF excitation pulse, the error in the B 1 + $$ {\mathrm{B}}_1^{+} $$ factor scales by approximately 3.8% for every 10 Hz/cm variation in B 0 $$ {\mathrm{B}}_0 $$ along the slice direction. Higher accuracy phantom B 1 + $$ {\mathrm{B}}_1^{+} $$ maps were obtained after applying the proposed correction; the root mean square B 1 + $$ {\mathrm{B}}_1^{+} $$ error relative to the gold standard B 1 + $$ {\mathrm{B}}_1^{+} $$ decreased from 6.4% to 2.6%. In vivo whole-liver T 1 $$ {\mathrm{T}}_1 $$ maps using the corrected B 1 + $$ {\mathrm{B}}_1^{+} $$ map registered a significant decrease in T 1 $$ {\mathrm{T}}_1 $$ gradient through slice. CONCLUSION: B 0 $$ {\mathrm{B}}_0 $$ inhomogeneities varying through slice were seen to have an impact on the accuracy of 2D double angle B 1 + $$ {\mathrm{B}}_1^{+} $$ maps using gradient-echo sequences. Consideration of this confounder is crucial for research relying on accurate knowledge of the true excitation flip angles, as is the case of T 1 $$ {\mathrm{T}}_1 $$ mapping using a spoiled gradient recalled echo sequence.

In vivo B 1 + enhancement of calf MRI at 7 T via optimized flexible metasurfaces.

PURPOSE: Ultrahigh field (≥7 T) MRI is at the cutting edge of medical imaging, enabling enhanced spatial and spectral resolution as well as enhanced susceptibility contrast. However, transmit ( B 1 + $$ {\mathrm{B}}_1^{+} $$ ) field inhomogeneity due to standing wave effects caused by the shortened RF wavelengths at 7 T is still a challenge to overcome. Novel hardware methods such as dielectric pads have been shown to improve the B 1 + $$ {\mathrm{B}}_1^{+} $$ field inhomogeneity but are currently limited in their corrective effect by the range of high-permittivity materials available and have a fixed shelf life. In this work, an optimized metasurface design is presented that demonstrates in vivo enhancement of the B 1 + $$ {\mathrm{B}}_1^{+} $$ field. METHODS: A prototype metasurface was optimized by an empirical capacitor sweep and by varying the period size. Phantom temperature experiments were performed to evaluate potential metasurface heating effects during scanning. Lastly, in vivo gradient echo images and B 1 + $$ {\mathrm{B}}_1^{+} $$ maps were acquired on five healthy subjects on a 7 T system. Dielectric pads were also used as a comparison throughout the work as a standard comparison. RESULTS: The metasurfaces presented here enhanced the average relative SNR of the gradient echo images by a factor of 2.26 compared to the dielectric pads factor of 1.61. Average B 1 + $$ {\mathrm{B}}_1^{+} $$ values reflected a similar enhancement of 27.6% with the metasurfaces present versus 8.9% with the dielectric pads. CONCLUSION: The results demonstrate that metasurfaces provide superior performance to dielectric padding as shown by B 1 + $$ {\mathrm{B}}_1^{+} $$ maps reflecting their direct effects and resulting enhancements in image SNR at 7 T.

Accelerated B 1 + $$ {\mathrm{B}}_1

PURPOSE: To investigate the impact of reduced k-space sampling on B 1 + $$ {\mathrm{B}}_1^{+} $$ mapping and the resulting impact on phase shimming and dynamic/universal parallel transmit (pTx) RF pulse design. METHODS: Channel-wise 3D B 1 + $$ {\mathrm{B}}_1^{+} $$ maps were measured at 7 T in 35 and 23 healthy subjects for the heart and prostate region, respectively. With these B 1 + $$ {\mathrm{B}}_1^{+} $$ maps, universal phase shims optimizing homogeneity and B 1 + $$ {\mathrm{B}}_1^{+} $$ efficiency were designed for heart and prostate imaging. In addition, universal 4kT-point pulses were designed for the heart. Subsequently, individual phase shims and individual 4kT-pulses were designed based on B 1 + $$ {\mathrm{B}}_1^{+} $$ maps with different acceleration factors and tested on the original maps. The performance of the pulses was compared by evaluating their coefficients of variation (CoV), B 1 + $$ {\mathrm{B}}_1^{+} $$ efficiencies and specific energy doses (SED). Furthermore, validation measurements were carried out for one heart and one prostate subject. RESULTS: For both organs, the universal phase shims showed significantly higher B 1 + $$ {\mathrm{B}}_1^{+} $$ efficiencies and lower CoVs compared to the vendor provided default shim, but could still be improved with individual phase shims based on accelerated B 1 + $$ {\mathrm{B}}_1^{+} $$ maps (acquisition time = 30 s). In the heart, the universal 4kT-pulse achieved significantly lower CoVs than tailored phase shims. Tailored 4kT-pulses based on accelerated B 1 + $$ {\mathrm{B}}_1^{+} $$ maps resulted in even further reduced CoVs or a 2.5-fold reduction in SED at the same CoVs as the universal 4kT-pulse. CONCLUSION: Accelerated B 1 + $$ {\mathrm{B}}_1^{+} $$ maps can be used for the design of tailored pTx pulses for prostate and cardiac imaging at 7 T, which further improve homogeneity, B 1 + $$ {\mathrm{B}}_1^{+} $$ efficiency, or SED compared to universal pulses.

Accelerated 3D multi-channel B 1 + mapping at 7 T for the brain and heart.

PURPOSE: To acquire accurate volumetric multi-channel B 1 + $$ {\mathrm{B}}_1^{+} $$ maps in under 14 s whole-brain or 23 heartbeats whole-heart for parallel transmit (pTx) applications at 7 T. THEORY AND METHODS: We evaluate the combination of three recently proposed techniques. The acquisition of multi-channel transmit array B 1 + $$ {\mathrm{B}}_1^{+} $$ maps is accelerated using transmit low rank (TxLR) with absolute B 1 + $$ {\mathrm{B}}_1^{+} $$ mapping (Sandwich) acquired in a B 1 + $$ {\mathrm{B}}_1^{+} $$ time-interleaved acquisition of modes (B1TIAMO) fashion. Simulations using synthetic body images derived from Sim4Life were used to test the achievable acceleration for small scan matrices of 24 × 24. Next, we evaluated the method by retrospectively undersampling a fully sampled B 1 + $$ {\mathrm{B}}_1^{+} $$ library of nine subjects in the brain. Finally, Cartesian undersampled phantom and in vivo images were acquired in both the brain of three subjects (8Tx/32 receive [Rx]) and the heart of another three subjects (8Tx/8Rx) at 7 T. RESULTS: Simulation and in vivo results show that volumetric multi-channel B 1 + $$ {\mathrm{B}}_1^{+} $$ maps can be acquired using acceleration factors of 4 in the body, reducing the acquisition time to within 23 heartbeats, which was previously not possible. In silico heart simulations demonstrated a RMS error to the fully sampled native resolution ground truth of 4.2° when combined in first-order circularly polarized mode (mean flip angle 66°) at an acceleration factor of 4. The 14 s 3D B 1 + $$ {\mathrm{B}}_1^{+} $$ maps acquired in the brain have a RMS error of 1.9° to the fully sampled (mean flip angle 86°). CONCLUSION: The proposed method is demonstrated as a fast pTx calibration technique in the brain and a promising method for pTx calibration in the body.

Accelerated 3D multi-echo spin-echo sequence with a subspace constrained reconstruction for whole mouse brain T 2 mapping.

PURPOSE: To accelerate whole-brain quantitative T 2 $$ {\mathrm{T}}_2 $$ mapping in preclinical imaging setting. METHODS: A three-dimensional (3D) multi-echo spin echo sequence was highly undersampled with a variable density Poisson distribution to reduce the acquisition time. Advanced iterative reconstruction based on linear subspace constraints was employed to recover high-quality raw images. Different subspaces, generated using exponential or extended-phase graph (EPG) simulations or from low-resolution calibration images, were compared. The subspace dimension was investigated in terms of T 2 $$ {\mathrm{T}}_2 $$ precision. The method was validated on a phantom containing a wide range of T 2 $$ {\mathrm{T}}_2 $$ and was then applied to monitor metastasis growth in the mouse brain at 4.7T. Image quality and T 2 $$ {\mathrm{T}}_2 $$ estimation were assessed for 3 acceleration factors (6/8/10). RESULTS: The EPG-based dictionary gave robust estimations of a large range of T 2 $$ {\mathrm{T}}_2 $$ . A subspace dimension of 6 was the best compromise between T 2 $$ {\mathrm{T}}_2 $$ precision and image quality. Combining the subspace constrained reconstruction with a highly undersampled dataset enabled the acquisition of whole-brain T 2 $$ {\mathrm{T}}_2 $$ maps, the detection and the monitoring of metastasis growth of less than 500 µ m 3 $$ \mu {\mathrm{m}}^3 $$ . CONCLUSION: Subspace-based reconstruction is suitable for 3D T 2 $$ {\mathrm{T}}_2 $$ mapping. This method can be used to reach an acceleration factor up to 8, corresponding to an acquisition time of 25 min for an isotropic 3D acquisition of 156 µ $$ \mu $$ m on the mouse brain, used here for monitoring metastases growth.

B1-MRF: Large dynamic range MRF-based absolute B 1 + mapping in the human body at 7T.

PURPOSE: This study aims to map the transmit magnetic field ( B 1 + $$ {B}_1^{+} $$ ) in the human body at 7T using MR fingerprinting (MRF), with a focus on achieving high accuracy and precision across a large dynamic range, particularly at low flip angles (FAs). METHODS: A FLASH-based MRF sequence (B1-MRF) with high B 1 + $$ {B}_1^{+} $$ sensitivity was developed. Phantom and in vivo abdominal imaging were performed at 7T, and the results were compared with established reference methods, including a slow but precise preparation-based method (PEX), saturated TurboFLASH (satTFL), actual flip angle imaging (AFI) and Bloch-Siegert shift (BSS). RESULTS: The MRF signal curve was highly sensitive to B 1 + $$ {B}_1^{+} $$ , while T1 sensitivity was comparatively low. The phantom experiment showed good agreement of B 1 + $$ {B}_1^{+} $$ to PEX for a T1 range of 204-1691 ms evaluated at FAs from 0° to 70°. Compared to the references, a dynamic range increase larger than a factor of two was determined experimentally. In vivo liver scans showed a strong correlation between B1-MRF, satTFL, and RPE-AFI in a low body mass index (BMI) subject (18.1 kg/m2). However, in larger BMI subjects (≥25.5 kg/m2), inconsistencies were observed in low B 1 + $$ {B}_1^{+} $$ regions for satTFL and RPE-AFI, while B1-MRF still provided consistent results in these regions. CONCLUSION: B1-MRF provides accurate and precise B 1 + $$ {B}_1^{+} $$ maps over a wide range of FAs, surpassing the capabilities of existing methods in the FA range < 60°. Its enhanced sensitivity at low FAs is advantageous for various applications requiring precise B 1 + $$ {B}_1^{+} $$ estimates, potentially advancing the frontiers of ultra-high field (UHF) body imaging at 7T and beyond.

Spiral 3DREAM sequence for fast whole-brain B1 mapping.

PURPOSE: This work demonstrates a new variant of the 3DREAM sequence for whole-brain B 1 + $$ {\mathrm{B}}_1^{+} $$ mapping employing a three-dimensional (3D) stack-of-spirals readout. The spiral readout reduces the echo train length after the STEAM preparation in order to overcome the significant blurring in STE* images due to the decreasing STE* signal with each excitation pulse. METHODS: The 3DREAM sequence rapidly acquires two contrasts to calculate whole-brain flip angle maps. In the proposed spiral 3DREAM sequence, the Cartesian readout scheme is replaced by an accelerated 3D stack-of-spirals readout with a CAIPIRINHA sampling scheme. Phantom experiments were conducted to compare flip angle maps of the spiral 3DREAM sequence to a Cartesian 3DREAM sequence, an actual flip-angle-imaging (AFI) sequence, the dual-angle method, and the Bloch-Siegert shift method. Afterwards, the results were validated in vivo acquiring flip angle maps from five subjects. RESULTS: Flip angle maps of the spiral 3DREAM sequences showed high agreement with the reference methods both in phantom and in vivo experiments. Blurring in STE* images and flip angle maps was reduced compared to the Cartesian 3DREAM sequence. CONCLUSION: The spiral 3DREAM sequence utilizes a fast readout minimizing the echo train length of the imaging train. This reduces blurring in STE* images as well as the total acquisition time and increases the effective resolution of B 1 + $$ {\mathrm{B}}_1^{+} $$ maps.

Impact of B 0 $$ {\mathrm{B}}_0 $$ field imperfections correction on BOLD sensitivity in 3D-SPARKLING fMRI data.

PURPOSE: Static and dynamic B 0 $$ {\mathrm{B}}_0 $$ field imperfections are detrimental to functional MRI (fMRI) applications, especially at ultra-high magnetic fields (UHF). In this work, a field camera is used to assess the benefits of retrospectively correcting B 0 $$ {\mathrm{B}}_0 $$ field perturbations on Blood Oxygen Level Dependent (BOLD) sensitivity in non-Cartesian three-dimensional (3D)-SPARKLING fMRI acquisitions. METHODS: fMRI data were acquired at 1 mm 3 $$ {}^3 $$ and for a 2.4s-TR while concurrently monitoring in real-time field perturbations using a Skope Clip-on field camera in a novel experimental setting involving a shorter TR than the required minimal TR of the field probes. Measurements of the dynamic field deviations were used along with a static Δ B 0 $$ \Delta {\mathrm{B}}_0 $$ map to retrospectively correct static and dynamic field imperfections, respectively. In order to evaluate the impact of such a correction on fMRI volumes, a comparative study was conducted on healthy volunteers. RESULTS: Correction of B 0 $$ {\mathrm{B}}_0 $$ deviations improved image quality and yielded between 20% and 30% increase in median temporal signal-to-noise ratio (tSNR).Using fMRI data collected during a retinotopic mapping experiment, we demonstrated a significant increase in sensitivity to the BOLD contrast and improved accuracy of the BOLD phase maps: 44% (resp., 159%) more activated voxels were retrieved when using a significance control level based on a p-value of 0.001 without correcting for multiple comparisons (resp., 0.05 with a false discovery rate correction). CONCLUSION: 3D-SPARKLING fMRI hugely benefits from static and dynamic B 0 $$ {\mathrm{B}}_0 $$ imperfections correction. However, the proposed experimental protocol is flexible enough to be deployed on a large spectrum of encoding schemes, including arbitrary non-Cartesian readouts.