Compact engineered human mechanosensitive transactivation modules enable potent and versatile synthetic transcriptional control.

Engineered transactivation domains (TADs) combined with programmable DNA binding platforms have revolutionized synthetic transcriptional control. Despite recent progress in programmable CRISPR-Cas-based transactivation (CRISPRa) technologies, the TADs used in these systems often contain poorly tolerated elements and/or are prohibitively large for many applications. Here, we defined and optimized minimal TADs built from human mechanosensitive transcription factors. We used these components to construct potent and compact multipartite transactivation modules (MSN, NMS and eN3x9) and to build the CRISPR-dCas9 recruited enhanced activation module (CRISPR-DREAM) platform. We found that CRISPR-DREAM was specific and robust across mammalian cell types, and efficiently stimulated transcription from diverse regulatory loci. We also showed that MSN and NMS were portable across Type I, II and V CRISPR systems, transcription activator-like effectors and zinc finger proteins. Further, as proofs of concept, we used dCas9-NMS to efficiently reprogram human fibroblasts into induced pluripotent stem cells and demonstrated that mechanosensitive transcription factor TADs are efficacious and well tolerated in therapeutically important primary human cell types. Finally, we leveraged the compact and potent features of these engineered TADs to build dual and all-in-one CRISPRa AAV systems. Altogether, these compact human TADs, fusion modules and delivery architectures should be valuable for synthetic transcriptional control in biomedical applications.

Diagnostic accuracy of prehospital lung ultrasound for acute decompensated heart failure: A systematic review and Meta-analysis.

BACKGROUND: Lung ultrasound (LUS) reduces time to diagnosis and treatment of acute decompensated heart failure (ADHF) in emergency department (ED) patients with undifferentiated dyspnea. We conducted a systematic review to evaluate the diagnostic accuracy and clinical impact of LUS for ADHF in the prehospital setting. METHODS: We performed a keyword search of multiple databases from inception through June 1, 2023. Included studies were those enrolling prehospital patients with undifferentiated dyspnea or suspected ADHF, and specifically diagnostic studies comparing prehospital LUS to a gold standard and intervention studies with a non-US comparator group. Title and abstract screening, full text review, risk of bias (ROB) assessments, and data extraction were performed by multiple authors. and adjudicated. The primary outcome was pooled sensitivity, specificity, and diagnostic likelihood ratios (LR) for prehospital LUS. A test-treatment threshold of 0.7 was applied based on prior ADHF literature in the ED. Intervention outcomes included mortality, mechanical ventilation, and time to HF specific treatment. RESULTS: Eight diagnostic studies (n = 691) and two intervention studies (n = 70) met inclusion criteria. No diagnostic studies were low-ROB. Both intervention studies were critical-ROB, and not pooled. Pooled sensitivity and specificity of prehospital LUS for ADHF were 86.7% (95%CI:70.8%-94.6%) and 87.5% (78.2%-93.2%), respectively, with similar performance by physician vs. paramedic LUS and number of lung zones evaluated. Pooled LR+ and LR- were 7.27 (95% CI: 3.69-13.10) and 0.17 (95% CI: 0.06-0.34), respectively. Area under the summary receiver operating characteristic curve was 0.922. At the observed 42.4% ADHF prevalence (pre-test probability), positive pre-hospital LUS exceeded the 70% threshold to initiate treatment (post-test probability 84%, 80-88%). CONCLUSIONS: LUS had similar diagnostic test characteristics for ADHF diagnosis in the prehospital setting as in the ED. A positive prehospital LUS may be sufficient to initiate early ADHF treatment based on published test-treatment thresholds. More studies are needed to determine the clinical impact of prehospital LUS.

Examining the effect of high-frequency information on the classification of conversationally produced English fricativesa).

This study examines the role of frequencies above 8 kHz in the classification of conversational speech fricatives [f, v, θ, ð, s, z, ʃ, ʒ, h] in random forest modeling. Prior research has mostly focused on spectral measures for fricative categorization using frequency information below 8 kHz. The contribution of higher frequencies has received only limited attention, especially for non-laboratory speech. In the present study, we use a corpus of sociolinguistic interview recordings from Western Canadian English sampled at 44.1 and 16 kHz. For both sampling rates, we analyze spectral measures obtained using Fourier analysis and the multitaper method, and we also compare models without and with amplitudinal measures. Results show that while frequency information above 8 kHz does not improve classification accuracy in random forest analyses, inclusion of such frequencies can affect the relative importance of specific measures. This includes a decreased contribution of center of gravity and an increased contribution of spectral standard deviation for the higher sampling rate. We also find no major differences in classification accuracy between Fourier and multitaper measures. The inclusion of power measures improves model accuracy but does not change the overall importance of spectral measures.

Temporal and spectral characteristics of conversational versus read fricatives in American English.

The present study compares the production of fricatives in conversational versus read speech in American English. The goal is to examine which parameters contribute to the identification of fricatives across the two speech styles. The study surveys over 162 000 fricative tokens from the Buckeye Corpus [Pitt, Johnson, Hume, Kiesling, and Raymond (2005). Speech Commun. 45, 89-95] and the TIMIT Corpus [Zue and Seneff (1996). Recent Research towards Advanced Man-Machine Interface through Spoken Language (Elsevier, Amsterdam, the Netherlands), pp. 515-525]. A total of 18 different temporal and spectral measures are tested, including segment duration, preceding and following phone duration, spectral moments (at onset, midpoint, and/or offset), spectral peak frequency, etc. Results show that segment duration and midpoint spectral moments make the most prominent contribution to the categorization of fricatives for both speech styles. Spectral measures are more important for conversational speech, whereas duration plays a greater role for read speech. At the same time, the magnitude of the differences across speech styles is often low and many of the observed effects may be attributable to methodological differences across the corpora. Results may indicate that reduction of fricatives in conversational speech is more limited compared to the reduction of other types of speech sounds, such as plosives.

Whole-brain B1 -mapping using three-dimensional DREAM.

PURPOSE: Demonstration of a 3D version of the DREAM sequence (3DREAM) for rapid 3D flip angle and B1+ mapping of the human brain. METHODS: A rectangular non-selective STE preparation is followed by a 3D readout with a Cartesian center-out spiral phase encoding order. This enables parallel imaging acceleration in both phase encoding dimensions as well as early capture of the prepared magnetization. RESULTS: B1+ mapping of the whole human head is demonstrated on a 7T system at a nominal resolution of 5 mm with and without parallel imaging acceleration. Artifacts caused by the different signal decay of the FID and STE signal during the long imaging train is suppressed by appropriate filtering of the FID image. Remaining blurring can be controlled by adjusting the echo train length and readout flip angle. CONCLUSIONS: 3DREAM provides a whole-brain flip angle map in a few seconds or individual maps for an 8-channel array in about a minute.

c-MPL provides tumor-targeted T-cell receptor-transgenic T cells with costimulation and cytokine signals.

Adoptively transferred T-cell receptor (TCR)-engineered T cells depend on host-derived costimulation and cytokine signals for their full and sustained activation. However, in patients with cancer, both signals are frequently impaired. Hence, we developed a novel strategy that combines both essential signals in 1 transgene by expressing the nonlymphoid hematopoietic growth factor receptor c-MPL (myeloproliferative leukemia), the receptor for thrombopoietin (TPO), in T cells. c-MPL signaling activates pathways shared with conventional costimulatory and cytokine receptor signaling. Thus, we hypothesized that host-derived TPO, present in the tumor microenvironment, or pharmacological c-MPL agonists approved by the US Food and Drug Administration could deliver both signals to c-MPL-engineered TCR-transgenic T cells. We found that c-MPL+ polyclonal T cells expand and proliferate in response to TPO, and persist longer after adoptive transfer in immunodeficient human TPO-transgenic mice. In TCR-transgenic T cells, c-MPL activation enhances antitumor function, T-cell expansion, and cytokine production and preserves a central memory phenotype. c-MPL signaling also enables sequential tumor cell killing, enhances the formation of effective immune synapses, and improves antileukemic activity in vivo in a leukemia xenograft model. We identify the type 1 interferon pathway as a molecular mechanism by which c-MPL mediates immune stimulation in T cells. In conclusion, we present a novel immunotherapeutic strategy using c-MPL-enhanced transgenic T cells responding to either endogenously produced TPO (a microenvironment factor in hematologic malignancies) or c-MPL-targeted pharmacological agents.

Stretchable multichannel antennas in soft wireless optoelectronic implants for optogenetics.

Optogenetic methods to modulate cells and signaling pathways via targeted expression and activation of light-sensitive proteins have greatly accelerated the process of mapping complex neural circuits and defining their roles in physiological and pathological contexts. Recently demonstrated technologies based on injectable, microscale inorganic light-emitting diodes (µ-ILEDs) with wireless control and power delivery strategies offer important functionality in such experiments, by eliminating the external tethers associated with traditional fiber optic approaches. Existing wireless µ-ILED embodiments allow, however, illumination only at a single targeted region of the brain with a single optical wavelength and over spatial ranges of operation that are constrained by the radio frequency power transmission hardware. Here we report stretchable, multiresonance antennas and battery-free schemes for multichannel wireless operation of independently addressable, multicolor µ-ILEDs with fully implantable, miniaturized platforms. This advance, as demonstrated through in vitro and in vivo studies using thin, mechanically soft systems that separately control as many as three different µ-ILEDs, relies on specially designed stretchable antennas in which parallel capacitive coupling circuits yield several independent, well-separated operating frequencies, as verified through experimental and modeling results. When used in combination with active motion-tracking antenna arrays, these devices enable multichannel optogenetic research on complex behavioral responses in groups of animals over large areas at low levels of radio frequency power (<1 W). Studies of the regions of the brain that are involved in sleep arousal (locus coeruleus) and preference/aversion (nucleus accumbens) demonstrate the unique capabilities of these technologies.

The Massive Auditory Lexical Decision (MALD) database.

The Massive Auditory Lexical Decision (MALD) database is an end-to-end, freely available auditory and production data set for speech and psycholinguistic research, providing time-aligned stimulus recordings for 26,793 words and 9592 pseudowords, and response data for 227,179 auditory lexical decisions from 231 unique monolingual English listeners. In addition to the experimental data, we provide many precompiled listener- and item-level descriptor variables. This data set makes it easy to explore responses, build and test theories, and compare a wide range of models. We present summary statistics and analyses.

SAR and scan-time optimized 3D whole-brain double inversion recovery imaging at 7T.

PURPOSE: The aim of this project was to implement an ultra-high field (UHF) optimized double inversion recovery (DIR) sequence for gray matter (GM) imaging, enabling whole brain coverage in short acquisition times ( ≈5 min, image resolution 1 mm3 ). METHODS: A 3D variable flip angle DIR turbo spin echo (TSE) sequence was optimized for UHF application. We implemented an improved, fast, and specific absorption rate (SAR) efficient TSE imaging module, utilizing improved reordering. The DIR preparation was tailored to UHF application. Additionally, fat artifacts were minimized by employing water excitation instead of fat saturation. RESULTS: GM images, covering the whole brain, were acquired in 7 min scan time at 1 mm isotropic resolution. SAR issues were overcome by using a dedicated flip angle calculation considering SAR and SNR efficiency. Furthermore, UHF related artifacts were minimized. CONCLUSION: The suggested sequence is suitable to generate GM images with whole-brain coverage at UHF. Due to the short total acquisition times and overall robustness, this approach can potentially enable DIR application in a routine setting and enhance lesion detection in neurological diseases. Magn Reson Med 79:2620-2628, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

GRAPPA reconstructed wave-CAIPI MP-RAGE at 7 Tesla.

PURPOSE: The aim of this project was to develop a GRAPPA-based reconstruction for wave-CAIPI data. Wave-CAIPI fully exploits the 3D coil sensitivity variations by combining corkscrew k-space trajectories with CAIPIRINHA sampling. It reduces artifacts and limits reconstruction induced spatially varying noise enhancement. The GRAPPA-based wave-CAIPI method is robust and does not depend on the accuracy of coil sensitivity estimations. METHODS: We developed a GRAPPA-based, noniterative wave-CAIPI reconstruction algorithm utilizing multiple GRAPPA kernels. For data acquisition, we implemented a fast 3D magnetization-prepared rapid gradient-echo wave-CAIPI sequence tailored for ultra-high field application. The imaging results were evaluated by comparing the g-factor and the root mean square error to Cartesian CAIPIRINHA acquisitions. Additionally, to assess the performance of subcortical segmentations (calculated by FreeSurfer), the data were analyzed across five subjects. RESULTS: Sixteen-fold accelerated whole brain magnetization-prepared rapid gradient-echo data (1 mm isotropic resolution) were acquired in 40 seconds at 7T. A clear improvement in image quality compared to Cartesian CAIPIRINHA sampling was observed. For the chosen imaging protocol, the results of 16-fold accelerated wave-CAIPI acquisitions were comparable to results of 12-fold accelerated Cartesian CAIPIRINHA. In comparison to the originally proposed SENSitivity Encoding reconstruction of Wave-CAIPI data, the GRAPPA approach provided similar image quality. CONCLUSION: High-quality, wave-CAIPI magnetization-prepared rapid gradient-echo images can be reconstructed by means of a GRAPPA-based reconstruction algorithm. Even for high acceleration factors, the noniterative reconstruction is robust and does not require coil sensitivity estimations. By altering the aliasing pattern, ultra-fast whole-brain structural imaging becomes feasible.

Modifiable and Nonmodifiable Factors Associated With Perioperative Failure of Extraglottic Airway Devices.

BACKGROUND: Extraglottic airway device (EGA) failure can be associated with severe complications and adverse patient outcomes. Prior research has identified patient- and procedure-related predictors of EGA failure. In this retrospective study, we assessed the incidence of perioperative EGA failure at our institution and identified modifiable factors associated with this complication that may be the target of preventative or mitigating interventions. METHODS: We performed a 5-year retrospective analysis of adult general anesthesia cases managed with EGAs in a single academic center. Univariable and multivariable logistic regressions were used to identify clinically modifiable and nonmodifiable factors significantly associated with 3 different types of perioperative EGA failure: (1) "EGA placement failure," (2) "EGA failure before procedure start," and (3) "EGA failure after procedure start." RESULTS: A total of 19,693 cases involving an EGA were included in the analysis dataset. EGA failure occurred in 383 (1.9%) of the cases. EGA placement failure occurred in 222 (1.13%) of the cases. EGA failure before procedure start occurred in 76 (0.39%) of the cases. EGA failure after procedure start occurred in 85 (0.43%) of the cases. Factors significantly associated with each type of failure and controllable by the anesthesia team were as follows: (1) EGA placement failure: use of desflurane (odds ratio [OR], 1.67; 95% confidence interval [CI], 1.23-2.25) and EGA size 4 or 5 vs 2 or 3 (OR, 0.07; 95% CI, 0.05-0.10); (2) EGA failure before procedure start: use of desflurane (OR, 2.05; 95% CI, 1.23-3.40) and 3 or more placement attempts (OR, 4.69; 95% CI, 2.57-8.56); and (3) EGA failure after procedure start: 3 or more placement attempts (OR, 2.06; 95% CI, 1.02-4.16) and increasing anesthesia time (OR, 1.35; 95% CI, 1.17-1.55). CONCLUSIONS: The overall incidence of EGA failure was 1.9%, and EGA placement failure was the most common type of failure. We also found that use of desflurane and use of smaller EGA sizes in adult patients were factors under the direct control of anesthesia clinicians associated with EGA failure. An increasing number of attempts at EGA placement was associated with later device failures. Our findings also confirm the association of EGA failure with previously identified patient- and procedure-related factors such as increased body mass index, male sex, and position other than supine.

Systematic review and meta-analysis of perioperative and long-term outcomes in patients receiving statin therapy before carotid endarterectomy.

BACKGROUND: Carotid endarterectomy (CEA) is associated with perioperative stroke and mortality in a minority of cases. The aim of this systematic review and meta-analysis was to investigate the effect of pre-operative statins on perioperative outcomes in patients undergoing CEA for internal carotid artery (ICA) stenosis. METHODS: A systematic review of PubMed, Medline, and the Cochrane Database of Systematic Reviews was performed. Studies were included which reported perioperative stroke and/or survival outcomes following CEA for ICA stenosis and compared patients who were and were not taking pre-operative statins. Relevant data were extracted and pooled using meta-analysis. RESULTS: Seven studies met the inclusion criteria, comprising 21,387 patients. A total of 68.9% (14,976) were administered statins and 31.1% (6657) were statin-free. Pre-operative statin use was higher in patients with a history of cardiac disease (12.2 vs. 23.6% in the statin-free group), diabetes (31.6 vs. 25.1% in the statin-free group), and hypertension (83.5 vs. 72.2% in the statin-free group), while a greater proportion of statin-free patients had symptomatic disease (44.9 vs. 55.5% in the statin-free group). Statins were associated with reduced perioperative stroke in all patients (OR 0.57; 95% CI 0.34-0.95; p = 0.03) and in symptomatic patients (OR 0.57; 95% CI 0.35-0.93; p = 0.03). A trend towards lower perioperative mortality (OR 0.54; 95% CI 0.29, 1.03; p = 0.06) and significantly improved overall survival was observed in the statin group (HR 0.69; 95% CI 0.59-0.81; p < 0.001) at a mean follow-up of 62 months (range 27-76 months). CONCLUSIONS: Administration of statins before CEA is associated with lower rates of perioperative stroke and improved overall survival. Compliance with optimal medical treatment associated with the use of pre-operative statins may limit the clinical significance of these findings. Future investigation to characterize the potential benefit of statin therapy in patients undergoing CEA for ICA stenosis is warranted.

Transfer accuracy of two indirect bonding techniques-an in vitro study with 3D scanned models.

Background and objectives: Indirect bonding (IDB) proved to be an effective method for appropriate bracket positioning in patients. Different methods and materials are available for fabricating transfer trays. This in vitro study was designed to measure and compare the transfer accuracy of two common IDB methods. Materials and methods: Sixty stone models were fabricated and separated in two groups of 30 models each (15 working models, 15 patient models). After placing brackets on the working models, 30 IDB trays were made: 15 silicone (method I) and 15 double-vacuum forms (method II). With these trays, the brackets were transferred to the patient models. The bracket positions were scanned before and after the IDB procedure with an intraoral scanner. The linear and angular discrepancies were then determined digitally by measuring six different dimensions: occluso-cervical, mesio-distal, bucco-lingual, tip, rotation, and torque. Results: The silicone trays showed fewer transfer discrepancies, on average, in all measured dimensions. There were significant differences between the methods in the occluso-cervical (P < 0.001), mesio-distal (P = 0.001), and torque (P = 0.044) dimensions. With both methods, 100 per cent of the horizontal and transversal measurements of both methods were within the clinically acceptable range of 0.25 mm. With method I, 98.5 per cent of the vertical and 95.9 per cent of the angular measurements were within the range of 0.25 mm and 1°, respectively. With method II, 94 per cent of the vertical and 84.8 per cent of the angular measurements were within the clinically acceptable range. Conclusions: Although both transfer methods showed a high precision, silicone trays scored better in terms of accuracy than double-vacuum forms.

Rapid whole-brain resting-state fMRI at 3 T: Efficiency-optimized three-dimensional EPI versus repetition time-matched simultaneous-multi-slice EPI.

State-of-the-art simultaneous-multi-slice (SMS-)EPI and 3D-EPI share several properties that benefit functional MRI acquisition. Both sequences employ equivalent parallel imaging undersampling with controlled aliasing to achieve high temporal sampling rates. As a volumetric imaging sequence, 3D-EPI offers additional means of acceleration complementary to 2D-CAIPIRINHA sampling, such as fast water excitation and elliptical sampling. We performed an application-oriented comparison between a tailored, six-fold CAIPIRINHA-accelerated 3D-EPI protocol at 530 ms temporal and 2.4 mm isotropic spatial resolution and an SMS-EPI protocol with identical spatial and temporal resolution for whole-brain resting-state fMRI at 3 T. The latter required eight-fold slice acceleration to compensate for the lack of elliptical sampling and fast water excitation. Both sequences used vendor-supplied on-line image reconstruction. We acquired test/retest resting-state fMRI scans in ten volunteers, with simultaneous acquisition of cardiac and respiration data, subsequently used for optional physiological noise removal (nuisance regression). We found that the 3D-EPI protocol has significantly increased temporal signal-to-noise ratio throughout the brain as compared to the SMS-EPI protocol, especially when employing motion and nuisance regression. Both sequence types reliably identified known functional networks with stronger functional connectivity values for the 3D-EPI protocol. We conclude that the more time-efficient 3D-EPI primarily benefits from reduced parallel imaging noise due to a higher, actual k-space sampling density compared to SMS-EPI. The resultant BOLD sensitivity increase makes 3D-EPI a valuable alternative to SMS-EPI for whole-brain fMRI at 3 T, with voxel sizes well below 3 mm isotropic and sampling rates high enough to separate dominant cardiac signals from BOLD signals in the frequency domain.

Application of the limited-memory quasi-Newton algorithm for multi-dimensional, large flip-angle RF pulses at 7T.

OBJECTIVE: Ultrahigh field MRI provides great opportunities for medical diagnostics and research. However, ultrahigh field MRI also brings challenges, such as larger magnetic susceptibility induced field changes. Parallel-transmit radio-frequency pulses can ameliorate these complications while performing advanced tasks in routine applications. To address one class of such pulses, we propose an optimal-control algorithm as a tool for designing advanced multi-dimensional, large flip-angle, radio-frequency pulses. We contrast initial conditions, constraints, and field correction abilities against increasing pulse trajectory acceleration factors. MATERIALS AND METHODS: On an 8-channel 7T system, we demonstrate the quasi-Newton algorithm with pulse designs for reduced field-of-view imaging with an oil phantom and in vivo with scans of the human brain stem. We used echo-planar imaging with 2D spatial-selective pulses. Pulses are computed sufficiently rapid for routine applications. RESULTS: Our dataset was quantitatively analyzed with the conventional mean-square-error metric and the structural-similarity index from image processing. Analysis of both full and reduced field-of-view scans benefit from utilizing both complementary measures. CONCLUSION: We obtained excellent outer-volume suppression with our proposed method, thus enabling reduced field-of-view imaging using pulse trajectory acceleration factors up to 4.

Comparison of accelerated T1-weighted whole-brain structural-imaging protocols.

Imaging in neuroscience, clinical research and pharmaceutical trials often employs the 3D magnetisation-prepared rapid gradient-echo (MPRAGE) sequence to obtain structural T1-weighted images with high spatial resolution of the human brain. Typical research and clinical routine MPRAGE protocols with ~1mm isotropic resolution require data acquisition time in the range of 5-10min and often use only moderate two-fold acceleration factor for parallel imaging. Recent advances in MRI hardware and acquisition methodology promise improved leverage of the MR signal and more benign artefact properties in particular when employing increased acceleration factors in clinical routine and research. In this study, we examined four variants of a four-fold-accelerated MPRAGE protocol (2D-GRAPPA, CAIPIRINHA, CAIPIRINHA elliptical, and segmented MPRAGE) and compared clinical readings, basic image quality metrics (SNR, CNR), and automated brain tissue segmentation for morphological assessments of brain structures. The results were benchmarked against a widely-used two-fold-accelerated 3T ADNI MPRAGE protocol that served as reference in this study. 22 healthy subjects (age=20-44yrs.) were imaged with all MPRAGE variants in a single session. An experienced reader rated all images of clinically useful image quality. CAIPIRINHA MPRAGE scans were perceived on average to be of identical value for reading as the reference ADNI-2 protocol. SNR and CNR measurements exhibited the theoretically expected performance at the four-fold acceleration. The results of this study demonstrate that the four-fold accelerated protocols introduce systematic biases in the segmentation results of some brain structures compared to the reference ADNI-2 protocol. Furthermore, results suggest that the increased noise levels in the accelerated protocols play an important role in introducing these biases, at least under the present study conditions.

Rapid fat suppression for three-dimensional echo planar imaging with minimized specific absorption rate.

PURPOSE: To investigate a method for rapid water excitation with minimal radiofrequency power deposition for efficient functional MRI at ultrahigh fields. THEORY AND METHODS: The suitability of the spectral response of a single rectangular radiofrequency pulse (rect) as a replacement of conventional fat saturation in segmented three-dimensional (3D) echo planar imaging (EPI) is explored. A pulse duration formula for lipid signal nulling independent of the small-tip-angle approximation is derived and tested by means of simulations and experiments at 3 and 7 Tesla (T). RESULTS: Compared with conventional binomial-11 water excitation, the single rect method is more selective and less sensitive to shim imperfections. In functional MRI, a significant measurement speedup (25%) and specific absorption rate reduction (from 44% to 1% at 7T) compared with conventional fat saturation are achieved. Furthermore, magnetization transfer effects are reduced resulting in up to 25% higher brain tissue signal-to-noise ratio. CONCLUSION: The proposed method is well suited for whole-brain functional MRI, not only at ultra-high fields, as it maximizes the sensitivity per unit time and at the same time minimizes radiofrequency power deposition. It requires little implementation effort and may thus be used in other spatially nonselective imaging methods that require fat suppression at minimal specific absorption rate and time requirements. Magn Reson Med 76:1517-1523, 2016. © 2015 International Society for Magnetic Resonance in Medicine.

Volumetric imaging with homogenised excitation and static field at 9.4 T.

OBJECTIVES: To overcome the challenges of B0 and RF excitation inhomogeneity at ultra-high field MRI, a workflow for volumetric B0 and flip-angle homogenisation was implemented on a human 9.4 T scanner. MATERIALS AND METHODS: Imaging was performed with a 9.4 T human MR scanner (Siemens Medical Solutions, Erlangen, Germany) using a 16-channel parallel transmission system. B0- and B1-mapping were done using a dual-echo GRE and transmit phase-encoded DREAM, respectively. B0 shims and a small-tip-angle-approximation kT-points pulse were calculated with an off-line routine and applied to acquire T1- and T 2 (*) -weighted images with MPRAGE and 3D EPI, respectively. RESULTS: Over six in vivo acquisitions, the B0-distribution in a region-of-interest defined by a brain mask was reduced down to a full-width-half-maximum of 0.10 ± 0.01 ppm (39 ± 2 Hz). Utilising the kT-points pulses, the normalised RMSE of the excitation was decreased from CP-mode's 30.5 ± 0.9 to 9.2 ± 0.7 % with all B 1 (+)  voids eliminated. The SNR inhomogeneities and contrast variations in the T1- and T 2 (*) -weighted volumetric images were greatly reduced which led to successful tissue segmentation of the T1-weighted image. CONCLUSION: A 15-minute B0- and flip-angle homogenisation workflow, including the B0- and B1-map acquisitions, was successfully implemented and enabled us to reduce intensity and contrast variations as well as echo-planar image distortions in 9.4 T images.