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Understanding the effects of white matter (WM) axon fibre microstructure on T1 relaxation is important for neuroimaging. Here, we have studied the interrelationship between T1 and axon fibre configurations at 3T and 7T. T1 and S0 (=signal intensity at zero TI) were computed from MP2RAGE images acquired with six inversion recovery times. Multishell diffusion MRI images were analysed for fractional anisotropy (FA); MD; V1; the volume fractions for the first (f 1 ), second (f 2 ) and third (f 3 ) fibre configuration; and fibre density cross-section images for the first (fdc 1 ), second (fdc 2 ) and third (fdc 3 ) fibres. T1 values were plotted as a function of FA, f 1 , f 2 , f 3 , fdc 1 , fdc 2 and fdc 3 to examine interrelationships between the longitudinal relaxation and the diffusion MRI microstructural measures. T1 values decreased with increasing FA, f 1 and f 2 in a nonlinear fashion. At low FA values (from 0.2 to 0.4), a steep shortening of T1 was followed by a shallow shortening by 6%-10% at both fields. The steep shortening was associated with decreasing S0 and MD. T1 also decreased with increasing fdc 1 values in a nonlinear fashion. Instead, only a small T1 change as a function of either f 3 or fdc 3 was observed. In WM areas selected by fdc 1 only masks, T1 was shorter than in those with fdc 2 /fdc 3 . In WM areas with high single fibre populations, as delineated by f 1 /fdc 1 masks, T1 was shorter than in tissue with high complex fibre configurations, as segmented by f 2 /fdc 2 or f 3 /fdc 3 masks. T1 differences between these WM areas are attributable to combined effects by T1 anisotropy and lowered FA. The current data show strong interrelationships between T1, axon fibre configuration and orientation in healthy WM. It is concluded that diffusion MRI microstructural measures are essential in the effort to interpret quantitative T1 images in terms of tissue state in health and disease., (© 2024 The Author(s). NMR in Biomedicine published by John Wiley & Sons Ltd.)

Researchers are rapidly developing and deploying highly portable MRI technology to conduct field-based research. The new technology will widen access to include new investigators in remote and unconventional settings and will facilitate greater inclusion of rural, economically disadvantaged, and historically underrepresented populations. To address the ethical, legal, and societal issues raised by highly accessible and portable MRI, an interdisciplinary Working Group (WG) engaged in a multi-year structured process of analysis and consensus building, informed by empirical research on the perspectives of experts and the general public. This article presents the WG's consensus recommendations. These recommendations address technology quality control, design and oversight of research, including safety of research participants and others in the scanning environment, engagement of diverse participants, therapeutic misconception, use of artificial intelligence algorithms to acquire and analyze MRI data, data privacy and security, return of results and managing incidental findings, and research participant data access and control., Competing Interests: M.S.R. is a founder and equity holder of Hyperfine, Vizma Life Sciences, Intact Data Services, and Q4ML. M.S.R. serves on the scientific advisory boards of ABQMR, Synex Medical, Nanalysis, and O2M Technologies. J.T.V. is a co-founder of MR Access, Inc. E.T. is a co-founder of Adialante., (© The Author(s) 2024. Published by Oxford University Press on behalf of Duke University School of Law, Harvard Law School, Oxford University Press, and Stanford Law School.)

Iron oxide nanoparticles (IONPs) have wide utility in applications from drug delivery to the rewarming of cryopreserved tissues. Due to the complex behavior of IONPs (e.g., uneven particle distribution and aggregation), further developments and clinical translation can be accelerated by having access to a noninvasive method for tissue IONP quantification. Currently, there is no low-cost method to nondestructively track IONPs in tissues across a wide range of concentrations. This work describes the performance of a low-cost, tabletop, longitudinally detected electron paramagnetic resonance (LOD-EPR) system to address this issue in the field of cryopreservation, which utilizes IONPs for rewarming of rat kidneys. A low-cost LOD-EPR system is realized via simultaneous transmit and receive using MHz continuous-wave transverse excitation with kHz modulation, which is longitudinally detected at the modulation frequency to provide both geometric and frequency isolation. The accuracy of LOD-EPR for IONP quantification is compared with NMR relaxometry. Solution measurements show excellent linearity ( R 2 > 0.99) versus Fe concentration for both measurements on EMG308 (a commercial nanoparticle), silica-coated EMG308, and PEG-coated EMG308 in water. The LOD-EPR signal intensity and NMR longitudinal relaxation rate constant ( R 1 ) of water are affected by particle coating, solution viscosity, and particle aggregation. R 1 remains linear but with a reduced slope when in cryoprotective agent (CPA) solution, whereas the LOD-EPR signal is relatively insensitive to this. R 1 does not correlate well with Fe concentration in rat kidney sections ( R 2 = 0.3487), while LOD-EPR does ( R 2 = 0.8276), with a linear regression closely matching that observed in solution and CPA.

Background/objective: The serotoninergic nervous system is known to play a role in the maintenance of rapid eye movement (REM) sleep. Serotoninergic projections are known to be vulnerable in synucleinopathies. To date, positron emission tomography (PET) studies using serotonin-specific tracers have not been reported in isolated REM sleep behavior disorder (iRBD)., Methods: We conducted a cross-sectional imaging study using serotonin transporter (SERT) 11 C-3-amino-4-(2-dimethylaminomethyl-phenylsulfaryl)-benzonitrile (DASB) PET to identify differences in serotonin system integrity between 11 participants with iRBD and 16 older healthy controls., Results: Participants with iRBD showed lower DASB distribution volume ratios (DVRs) in the total neocortical mantle [1.13 (SD: 0.07) vs. 1.19 (SD: 0.06); t = 2.33, p = 0.028)], putamen [2.07 (SD: 0.19) vs. 2.25 (SD: 0.18); t = 2.55, p = 0.017], and insula [1.26 (SD: 0.11) vs. 1.39 (SD: 0.09); t = 3.58, p = 0.001]. Paradoxical increases relative to controls were seen in cerebellar hemispheres [0.98 (SD: 0.04) vs. 0.95 (SD: 0.02); t = 2.93, p = 0.007)]. No intergroup differences were seen in caudate, substantia nigra, or other brainstem regions with the exception of the dorsal mesencephalic raphe [3.08 (SD: 0.53) vs. 3.47 (SD: 0.48); t = 2.00, p = 0.056] that showed a non-significant trend toward lower values in iRBD., Conclusions: Insular, neocortical, and striatal serotoninergic terminal loss may be common in prodromal synucleinopathies before the onset of parkinsonism or dementia. Given our small sample size, these results should be interpreted as hypothesis-generating/exploratory in nature., Competing Interests: MG serves as a coinvestigator with effort for the Parkinson Progression Markers Initiative 2.0 (PPMI 2.0) project. NB has received research funding from the National Institutes of Health (P50 NS123067, R01 AG073100, U01 AG061393), Department of Affairs (I01 RX001631), Parkinson’s Foundation, the Farmer Family Foundation Parkinson’s Research Initiative, and the Michael J. Fox Foundation. VK receives payment and a travel stipend from the Movement Disorders Society for his role as an Associate Editor on the journal Movement Disorders and receives research grant funding from the US National Institutes of Health (NIH) and the US Department of Veterans Affairs (VA). The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Cellular macroencapsulation devices, known as tissue engineered grafts (TEGs), enable the transplantation of allogeneic cells without the need for life-long systemic immunosuppression. Islet containing TEGs offer promise as a potential functional cure for type 1 diabetes. Previous research has indicated sustained functionality of implanted islets at high density in a TEG requires external supplementary oxygen delivery and an effective tool to monitor TEG oxygen levels. A proven oxygen-measurement approach employs a 19 F oxygen probe molecule (a perfluorocarbon) implanted alongside therapeutic cells to enable oxygen- and temperature- dependent NMR relaxometry. Although the approach has proved effective, the clinical translation of 19 F oxygen relaxometry for TEG monitoring will be limited by the current inaccessibility and high cost of MRI. Here, we report the development of an affordable, compact, and tabletop 19 F NMR relaxometry system for monitoring TEG oxygenation. The system uses a 0.5 T Halbach magnet with a bore diameter (19 cm) capable of accommodating the human arm, a potential site of future TEG implantation. 19 F NMR relaxometry was performed while controlling the temperature and oxygenation levels of a TEG using a custom-built perfusion setup. Despite the magnet's nonuniform field, a pulse sequence of broadband adiabatic full-passage pulses enabled accurate 19 F longitudinal relaxation rate (R 1 ) measurements in times as short as ∼2 min (R 1 vs oxygen partial pressure and temperature (R 2  > 0.98)). The estimated sensitivity of R 1 to oxygen changes at 0.5 T was 1.62-fold larger than the sensitivity previously reported for 16.4 T. We conclude that TEG oxygenation monitoring with a compact, tabletop 19 F NMR relaxometry system appears feasible., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Efrain Torres reports a relationship with Adialante LLC that includes: equity or stocks. Parker Jenkins reports a relationship with Adialante LLC that includes: equity or stocks. Dimitrios Sakellariou reports a relationship with RE Magnet Studio Ltd that includes: equity or stocks. Klearchos K. Papas reports a relationship with Procyon Technologies LLC that includes: equity or stocks., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Introduction: Subcutaneous macroencapsulation devices circumvent disadvantages of intraportal islet therapy. However, a curative dose of islets within reasonably sized devices requires dense cell packing. We measured internal PO2 of implanted devices, mathematically modeled oxygen availability within devices and tested the predictions with implanted devices containing densely packed human islets., Methods: Partial pressure of oxygen (PO2) within implanted empty devices was measured by noninvasive 19 F-MRS. A mathematical model was constructed, predicting internal PO2, viability and functionality of densely packed islets as a function of external PO2. Finally, viability was measured by oxygen consumption rate (OCR) in day 7 explants loaded at various islet densities., Results: In empty devices, PO2 was 12 mmHg or lower, despite successful external vascularization. Devices loaded with human islets implanted for 7 days, then explanted and assessed by OCR confirmed trends proffered by the model but viability was substantially lower than predicted. Co-localization of insulin and caspase-3 immunostaining suggested that apoptosis contributed to loss of beta cells., Discussion: Measured PO2 within empty devices declined during the first few days post-transplant then modestly increased with neovascularization around the device. Viability of islets is inversely related to islet density within devices., Competing Interests: KP is the co-founder and CEO of Procyon Technologies, LLC, a startup company focused on the development of oxygenated cell encapsulation devices. BW, who was a graduate student at the time of this study, is now employed by Sylvatica Biotech Inc. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author MG declared that he was an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (© 2023 Einstein, Steyn, Weegman, Suszynski, Sambanis, O'Brien, Avgoustiniatos, Firpo, Graham, Janecek, Eberly, Garwood, Putnam and Papas.)

This review describes targeted magnetic resonance imaging (tMRI) of small changes in the T 1 and the spatial properties of normal or near normal appearing white or gray matter in disease of the brain. It employs divided subtracted inversion recovery (dSIR) and divided reverse subtracted inversion recovery (drSIR) sequences to increase the contrast produced by small changes in T 1 by up to 15 times compared to conventional T 1 -weighted inversion recovery (IR) sequences such as magnetization prepared-rapid acquisition gradient echo (MP-RAGE). This increase in contrast can be used to reveal disease with only small changes in T 1 in normal appearing white or gray matter that is not apparent on conventional MP-RAGE, T 2 -weighted spin echo (T 2 -wSE) and/or fluid attenuated inversion recovery (T 2 -FLAIR) images. The small changes in T 1 or T 2 in disease are insufficient to produce useful contrast with conventional sequences. To produce high contrast dSIR and drSIR sequences typically need to be targeted for the nulling TI of normal white or gray matter, as well as for the sign and size of the change in T 1 in these tissues in disease. The dSIR sequence also shows high signal boundaries between white and gray matter. dSIR and drSIR are essentially T 1 maps. There is a nearly linear relationship between signal and T 1 in the middle domain (mD) of the two sequences which includes T 1 s between the nulling T 1 s of the two acquired IR sequences. The drSIR sequence is also very sensitive to reductions in T 1 produced by Gadolinium based contrast agents (GBCAs), and when used with rigid body registration to align three-dimensional (3D) isotropic pre and post GBCA images may be of considerable value in showing subtle GBCA enhancement. In serial MRI studies performed at different times, the high signal boundaries generated by dSIR and drSIR sequences can be used with rigid body registration of 3D isotropic images to demonstrate contrast arising from small changes in T 1 (without or with GBCA enhancement) as well as small changes in the spatial properties of normal tissues and lesions, such as their site, shape, size and surface. Applications of the sequences in cases of multiple sclerosis (MS) and methamphetamine dependency are illustrated. Using targeted narrow mD dSIR sequences, widespread abnormalities were seen in areas of normal appearing white matter shown with conventional T 2 -wSE and T 2 -FLAIR sequences. Understanding of the features of dSIR and drSIR images is facilitated by the use of their T 1 -bipolar filters; to explain their targeting, signal, contrast, boundaries, T 1 mapping and GBCA enhancement. Targeted MRI (tMRI) using dSIR and drSIR sequences may substantially improve clinical MRI of the brain by providing unequivocal demonstration of abnormalities that are not seen with conventional sequences., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-23-232/coif). JD serves as an unpaid editorial board member of Quantitative Imaging in Medicine and Surgery. MNJP is a scientific and technical adviser to Magnetica, Brisbane, Australia. GMB is a clinical consultant to Magnetica, Brisbane, Australia. The other authors have no conflicts of interest to declare., (2023 Quantitative Imaging in Medicine and Surgery. All rights reserved.)

Purpose: To improve intraoral transverse loop coil design for high-resolution dental MRI., Methods: The transverse intraoral loop coil (tLoop) was modified (mtLoop) by overlapping the feed port conductors, bending the posterior section, introducing a parallel plate capacitor, optimizing the insulation thickness, and using it in receive-only mode. In addition, an MR-silent insulation was introduced. The performances of the mtLoop and tLoop coils were compared in terms of sensitivity, image SNR, and eddy currents using electromagnetic simulations and MRI measurements at 3T., Results: The receive-only mode of the mtLoop increases the sensitivity at the apices of the roots, and the overlapped feed port design eliminated signal voids along the incisors. The bent posterior section with the parallel plate capacitor reduced the unwanted signal of the tongue by a factor of 2.3 in the selected region off interest and lowered the eddy currents by 10%. The proposed new coil provided higher SNR by elevenfold and 2.5-fold at the incisors and apices of the molar roots within the selected regions of interest, respectively, in the experiments, as well as improved comfort. Optimal insulation thickness was determined as 1 mm. With the mtLoop, a (250 μm) 3 isotropic resolution of the dental arch could be realized using a UTE sequence within 2 min total acquisition time. A T 2 -SPACE protocol with (350 μm) 2 in-plane resolution was also demonstrated., Conclusion: The proposed new coil offers higher SNR at the incisors and apices of the molar roots, less unwanted signals from tongue, lower eddy currents, and improved patient comfort., (© 2023 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)

Purpose: To design and implement a multi-coil (MC) array for B 0 field generation for image encoding and simultaneous advanced shimming in a novel 1.5T head-only MRI scanner., Methods: A 31-channel MC array was designed following the unique constraints of this scanner design: The vertically oriented magnet is very short, stopping shortly above the shoulders of a sitting subject, and includes a window for the subject to see through. Key characteristics of the MC hardware, the B 0 field generation capabilities, and thermal behavior, were optimized in simulations prior to its construction. The unit was characterized via bench testing. B 0 field generation capabilities were validated on a human 4T MR scanner by analysis of experimental B 0 fields and by comparing images for several MRI sequences acquired with the MC array to those acquired with the system's linear gradients., Results: The MC system was designed to produce a multitude of linear and nonlinear magnetic fields including linear gradients of up to 10 kHz/cm (23.5 mT/m) with MC currents of 5 A per channel. With water cooling it can be driven with a duty cycle of up to 74% and ramp times of 500 μs. MR imaging experiments encoded with the developed multi-coil hardware were largely artifact-free; residual imperfections were predictable, and correctable., Conclusion: The presented compact multi-coil array is capable of generating image encoding fields with amplitudes and quality comparable to clinical systems at very high duty cycles, while additionally enabling high-order B 0 shimming capabilities and the potential for nonlinear encoding fields., (© 2023 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)

Purpose: Recent studies indicate that T 1 in white matter (WM) is influenced by fiber orientation in B 0 . The purpose of the study was to investigate the interrelationships between axon fiber orientation in corpus callosum (CC) and T 1 relaxation time in humans in vivo as well as in rat brain ex vivo., Methods: Volunteers were scanned for relaxometric and diffusion MRI at 3 T and 7 T. Angular T 1 plots from WM were computed using fractional anisotropy and fiber-to-field-angle maps. T 1 and fiber-to-field angle were measured in five sections of CC to estimate the effects of inherently varying fiber orientations on T 1 within the same tracts in vivo. Ex vivo rat-brain preparation encompassing posterior CC was rotated in B 0 and T 1 , and diffusion MRI images acquired at 9.4 T. T 1 angular plots were determined at several rotation angles in B 0 ., Results: Angular T 1 plots from global WM provided reference for estimated fiber orientation-linked T 1 changes within CC. In anterior midbody of CC in vivo, where small axons are dominantly present, a shift in axon orientation is accompanied by a change in T 1 , matching that estimated from WM T 1 data. In CC, where large and giant axons are numerous, the measured T 1 change is about 2-fold greater than the estimated one. Ex vivo rotation of the same midsagittal CC region of interest produced angular T 1 plots at 9.4 T, matching those observed at 7 T in vivo., Conclusion: These data causally link axon fiber orientation in B 0 to the T 1 relaxation anisotropy in WM., (© 2023 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)

Demonstrated is a standalone RF self-interference canceller for simultaneous transmit and receive (STAR) magnetic resonance imaging (MRI) at 1.5T. Standalone STAR cancels the leakage signal directly coupled between transmit and receive RF coils. A cancellation signal, introduced by tapping the input of a transmit coil with a power divider, is manipulated with voltage-controlled attenuators and phase shifters to match the leakage signal in amplitude, 180° out of phase, to exhibit high isolation between the transmitter and receiver. The cancellation signal is initially generated by a voltage-controlled oscillator (VCO); therefore, it does not require any external RF or synchronization signals from the MRI console for calibration. The system employs a field programmable gate array (FPGA) with an on-board analog to digital converter (ADC) to calibrate the cancellation signal by tapping the receive signal, which contains the leakage signal. Once calibrated, the VCO is disabled and the transmit signal path switches to the MRI console for STAR MR imaging. To compensate for the changes of parameters in RF sequences after the automatic calibration and to further improve isolation, a wireless user board that uses an ESP32 microcontroller was built to communicate with the FPGA for final fine-tuning of the output state. The standalone STAR system achieved 74.2 dB of isolation with a 94 second calibration time. With such high isolation, in-vivo MR images were obtained with approximately 40 mW of RF peak power.

Liver cryopreservation has the potential to enable indefinite organ banking. This study investigated vitrification-the ice-free cryopreservation of livers in a glass-like state-as a promising alternative to conventional cryopreservation, which uniformly fails due to damage from ice formation or cracking. Our unique "nanowarming" technology, which involves perfusing biospecimens with cryoprotective agents (CPAs) and silica-coated iron oxide nanoparticles (sIONPs) and then, after vitrification, exciting the nanoparticles via radiofrequency waves, enables rewarming of vitrified specimens fast enough to avoid ice formation and uniformly enough to prevent cracking from thermal stresses, thereby addressing the two main failures of conventional cryopreservation. This study demonstrates the ability to load rat livers with both CPA and sIONPs by vascular perfusion, cool them rapidly to an ice-free vitrified state, and rapidly and homogenously rewarm them. While there was some elevation of liver enzymes (Alanine Aminotransferase) and impaired indocyanine green (ICG) excretion, the nanowarmed livers were viable, maintained normal tissue architecture, had preserved vascular endothelium, and demonstrated hepatocyte and organ-level function, including production of bile and hepatocyte uptake of ICG during normothermic reperfusion. These findings suggest that cryopreservation of whole livers via vitrification and nanowarming has the potential to achieve organ banking for transplant and other biomedical applications., (© 2022. The Author(s) under exclusive licence to Biomedical Engineering Society.)

A high degree of structural order by white matter (WM) fibre tracts creates a physicochemical environment where water relaxations are rendered anisotropic. Recently, angularly dependent longitudinal relaxation has been reported in human WM. We have characterised interrelationships between T1 relaxation and diffusion MRI microstructural indices at 3 and 7 T. Eleven volunteers consented to participate in the study. Multishell diffusion MR images were acquired with b-values of 0/1500/3000 and 0/1000/2000 s/mm 2 at 1.5 and 1.05 mm 3 isotropic resolutions at 3 and 7 T, respectively. DTIFIT was used to compute DTI indices; the fibre-to-field angle (θ FB ) maps were obtained using the principal eigenvector images. The orientations and volume fractions of multiple fibre populations were estimated using BedpostX in FSL, and the orientation dispersion index (ODI) was estimated using the NODDI protocol. MP2RAGE was used to acquire images for T1 maps at 1.0 and 0.9 mm 3 isotropic resolutions at 3 and 7 T, respectively. At 3 T, T1 as a function of θ FB in WM with high fractional anisotropy and one-fibre orientation volume fraction or low ODI shows a broad peak centred at 50 o , but a flat baseline at 0 o and 90 o . The broad peak amounted up to 7% of the mean T1. At 7 T, the broad peak appeared at 40 o and T1 in fibres running parallel to B0 was longer by up to 75 ms (8.3% of the mean T1) than in those perpendicular to the field. The peak at 40 o was approximately 5% of mean T1 (i.e., proportionally smaller than that at 54 o at 3 T). The data demonstrate T1 anisotropy in WM with high microstructural order at both fields. The angular patterns are indicative of the B0-dependency of T1 anisotropy. Thus myelinated WM fibres influence T1 contrast both by acting as a T1 contrast agent and rendering T1 dependent on fibre orientation with B0., (© 2022 The Authors. NMR in Biomedicine published by John Wiley & Sons Ltd.)

Intravenous high-dose methotrexate (HD-MTX) is a critical chemotherapeutic agent in hematological malignancies, however, data are lacking on how to predict and prevent toxicities such as kidney injury. We retrospectively analyzed 539 episodes of HD-MTX (≥1 g/m 2 ) delivered to 144 patients for treatment of prophylaxis of CNS hematological malignancy across three Australian institutions and correlated risk factors with toxicity. Clinically relevant (CTCAE v4.03 grade 2-4) nephrotoxicity occurred on 36 (7%) occasions and was mostly grade 2. Multivariate analysis revealed that doses ≥6 g/m 2 (HR 5.02, 95%CI 1.46-17.2, p  = 0.01) and interacting/nephrotoxic drugs (HR: 7.15, 91%CI: 2.18-23.512, p  = 0.001) were the only factors associated with nephrotoxicity. 48-hour methotrexate level, hypoalbuminemia and increasing age were associated with prolonged clearance but not nephrotoxicity. Mucositis, liver dysfunction and cytopenias were transient and mild in most cases. We have demonstrated that the most common risk factors for nephrotoxicity are modifiable which may assist clinical decision-making when administering this important drug.

Deep-seated tumors of the liver, brain, and other organ systems often recur after initial surgical, chemotherapeutic, radiation, or focal treatments. Repeating these treatments is often invasive and traumatic. We propose an iron oxide nanoparticle (IONP)-enhanced precipitating hydrophobic injectable liquid (PHIL, MicroVention inc.) embolic as a localized dual treatment implant for nutrient deprivation and multiple repeatable thermal ablation. Following a single injection, multiple thermal treatments can be repeated as needed, based on monitoring of tumor growth/recurrence. Herein we show the ability to create an injectable stable PHIL-IONP solution, monitor deposition of the PHIL-IONP precipitate dispersion by μCT, and gauge the IONP distribution within the embolic by magnetic resonance imaging. Once precipitated, the implant could be heated to reach therapeutic temperatures >8 °C for thermal ablation (clinical temperature of ∼45 °C), in a model disk and a 3D tumor bed model. Heat output was not affected by physiological conditions, multiple heating sessions, or heating at intervals over a 1 month duration. Further, in ex vivo mice hind-limb tumors, we could noninvasively heat the embolic to an "ablative" temperature elevation of 17 °C (clinically 54 °C) in the first 5 min and maintain the temperature rise over +8 °C (clinically a temperature of 45 °C) for longer than 15 min.

Study Objective: Identifying individuals with isolated rapid eye movement sleep behavioral disorder (iRBD) is an important clinical research priority for future synucleinopathy trials. Nevertheless, little is known about the breadth of clinical settings where diagnoses of iRBD are initially made., Methods: We conducted a retrospective cohort study using the electronic medical record system at the University of Michigan to identify patients aged ≥ 60 years with new diagnoses of iRBD between 2015 and 2020. We focused specifically on patients receiving primary care at the University of Michigan so that we might use the university's electronic medical record system to capture the full scope of their multispecialty care interactions and diagnoses in this integrated health care system. We used International Classification of Diseases, Ninth Revision and Tenth Revision, diagnosis codes to identify the time of initial clinical diagnosis., Results: We found that 62/105 (59.0%) diagnoses were made by a sleep specialist, 9 (8.6%) by neurologists, and 30 (29.5%) by generalists or primary care (29.5%) providers. In addition, 67/105 (63.8%) diagnoses were made in the context of having available polysomnography results, while the remainder was made on the basis of clinical symptoms alone. The prognostic implications of iRBD were documented in 40/105 (38.1%) encounter notes and were more likely to occur in sleep clinic settings (chi-square = 12.74; P < .001) than in other contexts., Conclusions: Initial iRBD diagnoses occur in varied clinical settings in an integrated health care system and are often made without a confirmatory polysomnogram. Documented prognostic counseling is seen most often in sleep medicine clinics. Synucleinopathy prevention trials may be best designed around a sleep clinic-focused recruitment approach., Citation: Havis I, Coates T, Wyant KJ, Spears CC, Garwood M, Kotagal V. Isolated REM sleep behavior disorder in North American older adults in an integrated health care system. J Clin Sleep Med. 2022;18(9):2173-2178., (© 2022 American Academy of Sleep Medicine.)

A frequency-swept longitudinal detection (LOD) EPR system is described for ultra-low field spectroscopy and relaxometry. With the capability of performing simultaneous transmit and receive with -80 dB isolation, this LOD-EPR can capture signals with decay constants in the nanosecond range and in theory even sub-nanosecond range, at fields close to the earth's magnetic field. The theoretical principles underlying this LOD-EPR are based on a fictitious field that accounts for the Z-axis magnetization polarized by a radiofrequency field alone. The electron spin relaxation time is obtained directly from a previously derived equation that describes the relationship between the relaxation time and the spectral peak position. Herein, the first frequency-swept LOD-EPR system is described in detail, along with experimental measurements of the short relaxation time (∼30 ns) of the free radical, 2,2-diphenyl-1-picrylhydrazyl, at zero to low field., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Understanding the link between the brain activity and behavior is a key challenge in modern neuroscience. Behavioral neuroscience, however, lacks tools to record whole-brain activity in complex behavioral settings. Here we demonstrate that a novel Multi-Band SWeep Imaging with Fourier Transformation (MB-SWIFT) functional magnetic resonance imaging (fMRI) approach enables whole-brain studies in spontaneously behaving head-fixed rats. First, we show anatomically relevant functional parcellation. Second, we show sensory, motor, exploration, and stress-related brain activity in relevant networks during corresponding spontaneous behavior. Third, we show odor-induced activation of olfactory system with high correlation between the fMRI and behavioral responses. We conclude that the applied methodology enables novel behavioral study designs in rodents focusing on tasks, cognition, emotions, physical exercise, and social interaction. Importantly, novel zero echo time and large bandwidth approaches, such as MB-SWIFT, can be applied for human behavioral studies, allowing more freedom as body movement is dramatically less restricting factor., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to disclose., (Copyright © 2022. Published by Elsevier Inc.)

To extend the preservation of donor hearts beyond the current 4-6 h, this paper explores heart cryopreservation by vitrification-cryogenic storage in a glass-like state. While organ vitrification is made possible by using cryoprotective agents (CPA) that inhibit ice during cooling, failure occurs during convective rewarming due to slow and non-uniform rewarming which causes ice crystallization and/or cracking. Here an alternative, "nanowarming", which uses silica-coated iron oxide nanoparticles (sIONPs) perfusion loaded through the vasculature is explored, that allows a radiofrequency coil to rewarm the organ quickly and uniformly to avoid convective failures. Nanowarming has been applied to cells and tissues, and a proof of principle study suggests it is possible in the heart, but proper physical and biological characterization especially in organs is still lacking. Here, using a rat heart model, controlled machine perfusion loading and unloading of CPA and sIONPs, cooling to a vitrified state, and fast and uniform nanowarming without crystallization or cracking is demonstrated. Further, nanowarmed hearts maintain histologic appearance and endothelial integrity superior to convective rewarming and indistinguishable from CPA load/unload control hearts while showing some promising organ-level (electrical) functional activity. This work demonstrates physically successful heart vitrification and nanowarming and that biological outcomes can be expected to improve by reducing or eliminating CPA toxicity during loading and unloading., Competing Interests: Conflict of Interest The authors declare no conflict of interest.

Purpose: Reduce expense and increase accessibility of MRI by eliminating pulsed field (B 0 ) gradient hardware., Methods: A radiofrequency imaging method is described that enables spatial encoding without B 0 gradients. This method, herein referred to as frequency-modulated Rabi-encoded echoes (FREE), utilizes adiabatic full passage pulses and a gradient in the RF field (B 1 ) to produce spatially dependent phase modulation, equivalent to conventional phase encoding. In this work, Cartesian phase encoding was accomplished using FREE in a multi-shot double spin-echo sequence. Theoretical analysis and computer simulations investigated the influence of resonance offset and B 1 -gradient steepness and magnitude on reconstruction quality, which limit other radiofrequency imaging methodologies. Experimentally, FREE was compared to conventional phase-encoded MRI on human visual cortex using a simple surface transceiver coil., Results: Image distortions occurred in FREE when using nonlinear B 1 fields where the phase dependence becomes nonlinear, but with minimal change in signal intensity. Resonance offset effects were minimal for Larmor frequencies within the adiabatic full-passage pulse bandwidth., Conclusion: For the first time, FREE enabled slice-selective 2D imaging of the human brain without a B 0 gradient in the y-direction. FREE achieved high resolution in regions where the B 1 gradient was steepest, whereas images were distorted in regions where nonlinearity in the B 1 gradient was significant. Given that FREE experiences no significant signal loss due to B 1 nonlinearities and resonance offset, image distortions shown in this work might be corrected in the future based on B 1 and B 0 maps., (© 2021 International Society for Magnetic Resonance in Medicine.)

Vitrification can dramatically increase the storage of viable biomaterials in the cryogenic state for years. Unfortunately, vitrified systems ≥3 mL like large tissues and organs, cannot currently be rewarmed sufficiently rapidly or uniformly by convective approaches to avoid ice crystallization or cracking failures. A new volumetric rewarming technology entitled "nanowarming" addresses this problem by using radiofrequency excited iron oxide nanoparticles to rewarm vitrified systems rapidly and uniformly. Here, for the first time, successful recovery of a rat kidney from the vitrified state using nanowarming, is shown. First, kidneys are perfused via the renal artery with a cryoprotective cocktail (CPA) and silica-coated iron oxide nanoparticles (sIONPs). After cooling at -40 °C min -1 in a controlled rate freezer, microcomputed tomography (µCT) imaging is used to verify the distribution of the sIONPs and the vitrified state of the kidneys. By applying a radiofrequency field to excite the distributed sIONPs, the vitrified kidneys are nanowarmed at a mean rate of 63.7 °C min -1 . Experiments and modeling show the avoidance of both ice crystallization and cracking during these processes. Histology and confocal imaging show that nanowarmed kidneys are dramatically better than convective rewarming controls. This work suggests that kidney nanowarming holds tremendous promise for transplantation., (© 2021 The Authors. Advanced Science published by Wiley-VCH GmbH.)

Purpose: The ability to use dual polarity encoded MRI with the missing pulse steady-state free precession (MP-SSFP) sequence is demonstrated to perform robust MRI with low radiofrequency (RF) amplitude, where the field is distorted by embedding metallic screws in an agar phantom. Image-based estimation of the 3D ΔB 0 map and image distortion correction is shown to require ~1 minute to perform., Theory and Methods: Dual polarity encoded MP-SSFP was implemented at 1.5T and used to image agar phantoms with one stainless steel and one titanium screw embedded inside. A multispectral fast spin-echo acquisition was performed for comparison. Self-consistent ΔB 0 estimation is performed iteratively using a 3D B-spline basis, which is compared to the ΔB 0 estimate generated by the multispectral sequence., Results: Dual polarity encoded MP-SSFP yields image quality similar to the multispectral sequence used with substantially less imaging time, provided the MP-SSFP experimental parameters are chosen well. The multispectral sequence appears to visualize modestly closer in proximity to the metallic screws used, despite the spectral bins covering the same bandwidth as the pulses used in MP-SSFP. However, MP-SSFP avoids ripple artifacts characteristic of the multispectral sequence. The ΔB 0 estimate generated by MP-SSFP is qualitatively similar to that generated by the multispectral sequence but larger in magnitude., Conclusion: Despite longer processing time compared to multispectral imaging, MP-SSFP yields similar image quality with significantly lower acquisition times in the absence of parallel imaging. The work herein demonstrates the ability to perform 3D ΔB 0 estimation and image correction within a reasonable amount of time, ~1 minute., (© 2021 International Society for Magnetic Resonance in Medicine.)

Smaller, more affordable, and more portable MRI brain scanners offer exciting opportunities to address unmet research needs and long-standing health inequities in remote and resource-limited international settings. Field-based neuroimaging research in low- and middle-income countries (LMICs) can improve local capacity to conduct both structural and functional neuroscience studies, expand knowledge of brain injury and neuropsychiatric and neurodevelopmental disorders, and ultimately improve the timeliness and quality of clinical diagnosis and treatment around the globe. Facilitating MRI research in remote settings can also diversify reference databases in neuroscience, improve understanding of brain development and degeneration across the lifespan in diverse populations, and help to create reliable measurements of infant and child development. These deeper understandings can lead to new strategies for collaborating with communities to mitigate and hopefully overcome challenges that negatively impact brain development and quality of life. Despite the potential importance of research using highly portable MRI in remote and resource-limited settings, there is little analysis of the attendant ethical, legal, and social issues (ELSI). To begin addressing this gap, this paper presents findings from the first phase of an envisioned multi-staged and iterative approach for creating ethical and legal guidance in a complex global landscape. Section 1 provides a brief introduction to the emerging technology for field-based MRI research. Section 2 presents our methodology for generating plausible use cases for MRI research in remote and resource-limited settings and identifying associated ELSI issues. Section 3 analyzes core ELSI issues in designing and conducting field-based MRI research in remote, resource-limited settings and offers recommendations. We argue that a guiding principle for field-based MRI research in these contexts should be including local communities and research participants throughout the research process in order to create sustained local value. Section 4 presents a recommended path for the next phase of work that could further adapt these use cases, address ethical and legal issues, and co-develop guidance in partnership with local communities., Competing Interests: Declaration of Competing Interest FXS and SMW disclose NIH/NIMH grant RF1MH123698 on “Highly Portable and Cloud-Enabled Neuroimaging Research: Confronting Ethics in Field Research with New Populations” (Shen, Wolf, Lawrenz, PIs). SD receives grant support from Nestlé Nutrition. DF is a patent holder on the Framewise Integrated Real-Time Motion Monitoring (FIRMM) software. He is also a co-founder of Nous Imaging Inc. The nature of this financial interest and the design of the study have been reviewed by two committees at the University of Minnesota. They have put in place a plan to help ensure that this research study is not affected by the financial interest. KR discloses that she is funded by The Kavli Foundation. KS is an employee of Hyperfine Research, Inc., (Copyright © 2021. Published by Elsevier Inc.)

Model-based reconstruction methods have emerged as a powerful alternative to classical Fourier-based MRI techniques, largely because of their ability to explicitly model (and therefore, potentially overcome) moderate field inhomogeneities, streamline reconstruction from non-Cartesian sampling, and even allow for the use of custom designed non-Fourier encoding methods. Their application in such scenarios, however, often comes with a substantial increase in computational cost, owing to the fact that the corresponding forward model in such settings no longer possesses a direct Fourier Transform based implementation. This paper introduces an algorithmic framework designed to reduce the computational burden associated with model-based MRI reconstruction tasks. The key innovation is the strategic sparsification of the corresponding forward operators for these models, giving rise to approximations of the forward models (and their adjoints) that admit low computational complexity application. This enables overall a reduced computational complexity application of popular iterative first-order reconstruction methods for these reconstruction tasks. Computational results obtained on both synthetic and experimental data illustrate the viability and efficiency of the approach.

Objective: In dental MRI, intraoral coils provide higher signal-to-noise ratio (SNR) than coils placed outside the mouth. This study aims to design an intraoral dipole antenna and demonstrates the feasibility of combining it with an extraoral coil., Methods: Dipole antenna design was chosen over loop design, as it is open toward the distal; therefore, it does not restrain tongue movement. The dipole design offers also an increased depth-of-sensitivity that allows for MRI of dental roots. Different dipole antenna designs were simulated using a finite-difference-time-domain approach. Ribbon, wire, and multi-wire arms were compared. The best design was improved further by covering the ends of the dipole arms with a high-permittivity material. Phantom and in vivo measurements were conducted on a 3T clinical MRI system., Results: The best transmit efficiency and homogeneity was achieved with a multi-wire curved dipole antenna with 7 wires for each arm. With an additional high-permittivity cap the transmit field inhomogeneity was further reduced from 20% to 5% along the dipole arm. When combined with extraoral flexible surface-coil, the coupling between the coils was less than -32dB and SNR was increased., Conclusion: Using intraoral dipole design instead of loop improves patient comfort. We demonstrated feasibility of the intraoral dipole combined with an extraoral flexible coil-array for dental MRI. Dipole antenna enabled decreasing imaging field-of-view, and reduced the prevalent signal from tongue., Significance: This study highlights the advantages and the main challenges of the intraoral RF coils and describes a novel RF coil that addresses those challenges.

Purpose: To develop a 3D composite adiabatic spectral-spatial pulse for refocusing in spin-echo spectroscopy acquisitions and to compare its performance against standard acquisition methods., Methods: A 3D composite adiabatic pulse was designed by modulating a train of parallel transmit-optimized 2D subpulses with an adiabatic envelope. The spatial and spectral profiles were simulated and validated by experiments to demonstrate the feasibility of the design in both single and double spin-echo spectroscopy acquisitions. Phantom and in vivo studies were performed to evaluate the pulse performance and compared with semi-LASER with respect to localization performance, sequence timing, signal suppression, and specific absorption rate., Results: Simultaneous 2D spatial localization with water and lipid suppression was achieved with the designed refocusing pulse, allowing high-quality spectra to be acquired with shorter minimum TE/TR, reduced SAR, as well as adaptation to spatially varying B 0 and B 1 + field inhomogeneities in both prostate and brain studies., Conclusion: The proposed composite pulse can serve as a more SAR efficient alternative to conventional localization methods such as semi-LASER at ultrahigh field for spin echo-based spectroscopy studies. Subpulse parallel-transmit optimization provides the flexibility to manage the tradeoff among multiple design criteria to accommodate different field strengths and applications., (© 2021 International Society for Magnetic Resonance in Medicine.)

Purpose: We demonstrate the feasibility of MRI with missing-pulse steady-state free precession (MP-SSFP) in a 4T magnet with artificially degraded homogeneity., Methods: T 1 , T 2 , and diffusion contrast of MP-SSFP was simulated with constant and alternate radiofrequency (RF) phase using an extended phase graph. To validate MP-SSFP performance in human brain imaging, MP-SSFP was tested with two types of artificially introduced inhomogeneous magnetic fields: (1) a pure linear gradient field, and (2) a pseudo-linear gradient field introduced by mounting a head-gradient set at 36 cm from the magnet isocenter. Image distortion induced by the nonlinear inhomogeneous field was corrected using B 0 mapping measured with MP-SSFP., Results: The maximum flip angle in MP-SSFP was limited to ≤10° because of the large range of resonance frequencies in the inhomogeneous magnetic fields tested in this study. Under this flip-angle limitation, MP-SSFP with constant RF phase provided advantages of higher signal-to-noise ratio and insensitivity to B 1 field inhomogeneity as compared with an alternate RF phase. In diffusion simulation, the steady-state magnetization in constant RF phase MP-SSFP increased with an increase of static field gradient up to 8 to 21 mT/m depending on simulation parameters. Experimental results at 4T validated these findings. In human brain imaging, MP-SSFP preserved sufficient signal intensities, but images showed severe image distortion from the pseudo-linear inhomogeneous field. However, following distortion correction, good-quality brain images were achieved.+ field inhomogeneity as compared with an alternate RF phase. In diffusion simulation, the steady-state magnetization in constant RF phase MP-SSFP increased with an increase of static field gradient up to 8 to 21 mT/m depending on simulation parameters. Experimental results at 4T validated these findings. In human brain imaging, MP-SSFP preserved sufficient signal intensities, but images showed severe image distortion from the pseudo-linear inhomogeneous field. However, following distortion correction, good-quality brain images were achieved., Conclusion: MP-SSFP appears to be a feasible MRI technique for brain imaging in an inhomogeneous magnetic field., (© 2020 International Society for Magnetic Resonance in Medicine.)

When viewed in a rotating frame of reference, a transverse-plane radiofrequency (RF) field manifests as a longitudinal field component called the fictitious field. By modulating the RF field and thus the fictitious field, detectable longitudinal magnetization patterns have previously been shown to be measurable. By combining fictitious-field modulation and longitudinal detection, here we demonstrate EPR spectroscopy and one-dimensional imaging in a custom-built longitudinal detection system operating at an ultra-low frequency (24 MHz) for detecting electron spins with short (~nanoseconds) relaxation times. Simultaneous transmit and receive with low transmitter leakage level (~80 dB isolation) is also demonstrated., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: Spatial encoding for MRI is generally based on linear x, y, and z magnetic field gradients generated by a set of dedicated gradient coils. We recently introduced the dynamic multicoil technique (DYNAMITE) for B 0 field control and demonstrated DYNAMITE MRI in a preclinical MR environment. In this study, we report the first realization of DYNAMITE MRI of the in vivo human head., Methods: Gradient fields for DYNAMITE MRI were generated with a 28-channel multicoil hardware arranged in 4 rows of 7 coils on a cylindrical surface (length 359 mm, diameter 344 mm, maximum 5 A per coil). DYNAMITE MRIs of a resolution phantom and in vivo human heads were acquired with multislice gradient-echo, multislice spin-echo, and 3D gradient-echo sequences. The resultant image fidelity was compared to that obtained with conventional gradient coil technology., Results: DYNAMITE field control enabled the realization of all imaging sequences with average gradient errors ≤ 1%. DYNAMITE MRI provided image quality and sensitivity comparable to conventional gradient technology without any obvious artifacts. Some minor geometric deformations were noticed primarily in the image periphery as the result of regional field imperfections. The imperfections can be readily approximated theoretically through numerical integration of the Biot-Savart law and removed through image distortion correction., Conclusion: The first realization of DYNAMITE MRI of the in vivo human head has been presented. The obtained image fidelity is comparable to MRI with conventional gradient coils, paving the way for full-fledged DYNAMITE MRI and B 0 shim systems for human applications., (© 2020 International Society for Magnetic Resonance in Medicine.)

Despite its importance as a clinical imaging modality, magnetic resonance imaging remains inaccessible to most of the world's population due to its high cost and infrastructure requirements. Substantial effort is underway to develop portable, low-cost systems able to address MRI access inequality and to enable new uses of MRI such as bedside imaging. A key barrier to development of portable MRI systems is increased magnetic field inhomogeneity when using small polarizing magnets, which degrades image quality through distortions and signal dropout. Many approaches address field inhomogeneity by using a low polarizing field, approximately ten to hundreds of milli-Tesla. At low-field, even a large relative field inhomogeneity of several thousand parts-per-million (ppm) results in resonance frequency dispersion of only 1-2 kHz. Under these conditions, with necessarily wide pulse bandwidths, fast spin-echo sequences may be used at low field with negligible subject heating, and a broad range of other available imaging sequences can be implemented. However, high-field MRI, 1.5 T or greater, can provide substantially improved signal-to-noise ratio and image contrast, so that higher spatial resolution, clinical quality images may be acquired in significantly less time than is necessary at low-field. The challenge posed by small, high-field systems is that the relative field inhomogeneity, still thousands of ppm, becomes tens of kilohertz over the imaging volume. This article describes the physical consequences of field inhomogeneity on established gradient- and spin-echo MRI sequences, and suggests ways to reduce signal dropout and image distortion from field inhomogeneity. Finally, the practicality of currently available image contrasts is reviewed when imaging with a high magnetic field with large inhomogeneity., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Frequency-modulated (FM) pulses can provide several advantages over conventional amplitude-modulated pulses in the field of MRI; however, the manner in which spins are manipulated imprints a quadratic phase on the resulting magnetization. Historically this was considered a hindrance and slowed the widespread adoption of FM pulses. This article seeks to provide a historical perspective of the different techniques that researchers have used to exploit the benefits of FM pulses and to compensate for the nonlinear phase created by this class of pulses in MRI. Expanding on existing techniques, a new method of phase compensation is presented that utilizes nonlinear gradients to mitigate the undesirable phase imparted by this class of pulses., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: Herein, we evaluate the use of MRI as a tool for assessing iron oxide nanoparticle (IONP) distribution within IONP perfused organs and vascularized composite allografts (VCAs) (i.e., hindlimbs) prepared for cryopreservation., Methods: Magnetic resonance imaging was performed on room-temperature organs and VCAs perfused with IONPs and were assessed at 9.4 T. Quantitative T 1 mapping and T 2 ∗ -weighted images were acquired using sweep imaging with Fourier transformation and gradient-echo sequences, respectively. Verification of IONP localization was performed through histological assessment and microcomputer tomography., Results: Quantitative imaging was achieved for organs and VCAs perfused with up to 642 mM Fe (36 mg Fe /mL), which is above previous demonstrations of upper limit detection in agarose (35.7mM Fe [2 mg Fe /mL]). The stability of IONPs in the perfusate had an effect on the quality of distribution and imaging within organs or VCA. Finally, MRI provided more accurate IONP localization than Prussian blue histological staining in this system, wherein IONPs remain primarily in the vasculature., Conclusion: Using MRI, we were able to assess the distribution of IONPs throughout organs and VCAs varying in complexity. Additional studies are necessary to better understand this system and validate the calibration between T 1 measurements and IONP concentration., (© 2019 International Society for Magnetic Resonance in Medicine.)

Highly portable, cloud-enabled neuroimaging technologies will fundamentally change neuroimaging research. Instead of participants traveling to the scanner, the scanner will now come to them. Field-based brain imaging research, including populations underrepresented in neuroscience research to date, will enlarge and diversify databases and pave the way for clinical and direct-to-consumer (DTC) applications. Yet these technological developments urgently require analysis of their ethical, legal, and social implications (ELSI). No consensus ethical frameworks for mobile neuroimaging exist, and existing policies for traditional MRI research are inadequate. Based on literature review and ethics analysis of neurotechnology development efforts, Shen et al. identify seven foundational, yet unresolved, ELSI issues posed by portable neuroimaging: (1) informed consent; (2) privacy; (3) capacity to accurately communicate neuroimaging results to remote participants; (4) extensive reliance on cloud-based artificial intelligence (AI) for data analysis; (5) potential bias of interpretive algorithms in diverse populations; (6) return of research results and incidental (or secondary) findings to research participants; and (7) responding to participant requests for access to their data. The article proposes a path forward to address these urgent issues., (Copyright © 2020. Published by Elsevier Inc.)

Reducing the echo time of magnetic resonance spectroscopy experiments is appealing because it increases the available signal and reduces J-evolution of coupled metabolites. In this manuscript a novel sequence, referred to as Ultrashort echo TimE, SPin ECho, full Intensity Acquired Localized (UTE-SPECIAL), is described which is able to achieve ultrashort echo times (4 ms) on a standard clinical 3 T MR system while recovering the entirety of the available magnetization. UTE-SPECIAL obtains full 3D spatial localization through a 2D adiabatic inversion pulse which is cycled "on" and "off" every other repetition, in combination with a slice-selective excitation pulse. In addition to an ultrashort echo time, UTE-SPECIAL has negligible chemical shift displacement artefact and, because it uses no slice-selective refocusing pulse, has no signal cancellation at the borders for J-coupled metabolites. Spectra with an ultrashort echo time of 4 ms are demonstrated in vivo at 3 T, as well as J-resolved spectra obtained in a phantom and a healthy volunteer., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Functional magnetic resonance imaging (fMRI) studies in animal models provide invaluable information regarding normal and abnormal brain function, especially when combined with complementary stimulation and recording techniques. The echo planar imaging (EPI) pulse sequence is the most common choice for fMRI investigations, but it has several shortcomings. EPI is one of the loudest sequences and very prone to movement and susceptibility-induced artefacts, making it suboptimal for awake imaging. Additionally, the fast gradient-switching of EPI induces disrupting currents in simultaneous electrophysiological recordings. Therefore, we investigated whether the unique features of Multi-Band SWeep Imaging with Fourier Transformation (MB-SWIFT) overcome these issues at a high 9.4 T magnetic field, making it a potential alternative to EPI. MB-SWIFT had 32-dB and 20-dB lower peak and average sound pressure levels, respectively, than EPI with typical fMRI parameters. Body movements had little to no effect on MB-SWIFT images or functional connectivity analyses, whereas they severely affected EPI data. The minimal gradient steps of MB-SWIFT induced significantly lower currents in simultaneous electrophysiological recordings than EPI, and there were no electrode-induced distortions in MB-SWIFT images. An independent component analysis of the awake rat functional connectivity data obtained with MB-SWIFT resulted in near whole-brain level functional parcellation, and simultaneous electrophysiological and fMRI measurements in isoflurane-anesthetized rats indicated that MB-SWIFT signal is tightly linked to neuronal resting-state activity. Therefore, we conclude that the MB-SWIFT sequence is a robust preclinical brain mapping tool that can overcome many of the drawbacks of conventional EPI fMRI at high magnetic fields., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: We have utilized a noninvasive technique for measuring the partial pressure of oxygen (pO2) in alginate microcapsules implanted intraperitoneally in healthy nonhuman primates (NHPs). Average pO2 is important for determining if a transplant site and capsules with certain passive diffusion characteristics can support the islet viability, metabolic activity, and dose necessary to reverse diabetes., Methods: Perfluoro-15-crown-5-ether alginate capsules were infused intraperitoneally into 3 healthy NHPs. Peritoneal pO2 levels were measured on days 0 and 7 using fluorine-19 magnetic resonance relaxometry and a fiber-optic probe. Fluorine-19 MRI was used to determine the locations of capsules within the peritoneal space on days 0 and 7. Gross and histologic evaluations of the capsules were used to assess their biocompatibility postmortem., Results: At day 0 immediately after infusion of capsules equilibrated to room air, capsules were concentrated near the infusion site, and the pO2 measurement using magnetic resonance relaxometry was 147 ± 9 mm Hg. On day 7 after capsules were dispersed throughout the peritoneal cavity, the pO2 level was 61 ± 11 mm Hg. Measurements using the fiber-optic oxygen sensor were 132 ± 7.5 mm Hg (day 0) and 89 ± 6.1 mm Hg (day 7). Perfluoro-15-crown-5-ether capsules retrieved on day 7 were intact and free-floating without host cell attachment, although the numbers of peritoneal CD20 B cells, CD4 and CD8 T cells, and CD14 macrophages increased consistent with a mild foreign body reaction., Conclusions: The peritoneal pO2 of normal NHPs is relatively low and we predict would decrease further when encapsulated islets are transplanted intraperitoneally.

Cryopreservation technology allows long-term banking of biological systems. However, a major challenge to cryopreserving organs remains in the rewarming of large volumes (>3 mL), where mechanical stress and ice formation during convective warming cause severe damage. Nanowarming technology presents a promising solution to rewarm organs rapidly and uniformly via inductive heating of magnetic nanoparticles (IONPs) preloaded by perfusion into the organ vasculature. This use requires the IONPs to be produced at scale, heat quickly, be nontoxic, remain stable in cryoprotective agents (CPAs), and be washed out easily after nanowarming. Nanowarming of cells and blood vessels using a mesoporous silica-coated iron oxide nanoparticle (msIONP) in VS55, a common CPA, has been previously demonstrated. However, production of msIONPs is a lengthy, multistep process and provides only mg Fe per batch. Here, a new microporous silica-coated iron oxide nanoparticle (sIONP) that can be produced in as little as 1 d while scaling up to 1.4 g Fe per batch is presented. sIONP high heating, biocompatibility, and stability in VS55 is also verified, and the ability to perfusion load and washout sIONPs from a rat kidney as evidenced by advanced imaging and ICP-OES is demonstrated., Competing Interests: The authors declare no conflict of interest., (© 2020 The Authors. Published by WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim.)

Large magnetic field inhomogeneity can be a significant cause of spatial flip-angle variation when using ordinary, limited-bandwidth RF pulses. Multidimensional RF pulses are particularly sensitive to inhomogeneity due to their extended pulse length, which decreases their bandwidth. Previously, it was shown that, by breaking a 2D pulse into multiple undersampled k-space segments, the excitation bandwidth can be increased at the expense of increased imaging time. The present study shows how this increased imaging time can be offset by undersampling acquisition k-space in a phase-encoded dimension that is in the direction of excitation segmentation. Data from each segment are viewed as originating from "virtual receive coils" rather than multiple physical coils. The undersampled data are reconstructed using parallel imaging techniques (e.g. as in GRAPPA). The method was tested in vivo with brain imaging at both 3 T and 4 T, and used in conjunction with a 32-channel head coil and conventional GRAPPA on the 3 T data. Relationships with existing techniques and future applications are discussed., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Understanding the diversity of cell types in the brain has been an enduring challenge and requires detailed characterization of individual neurons in multiple dimensions. To systematically profile morpho-electric properties of mammalian neurons, we established a single-cell characterization pipeline using standardized patch-clamp recordings in brain slices and biocytin-based neuronal reconstructions. We built a publicly accessible online database, the Allen Cell Types Database, to display these datasets. Intrinsic physiological properties were measured from 1,938 neurons from the adult laboratory mouse visual cortex, morphological properties were measured from 461 reconstructed neurons, and 452 neurons had both measurements available. Quantitative features were used to classify neurons into distinct types using unsupervised methods. We established a taxonomy of morphologically and electrophysiologically defined cell types for this region of the cortex, with 17 electrophysiological types, 38 morphological types and 46 morpho-electric types. There was good correspondence with previously defined transcriptomic cell types and subclasses using the same transgenic mouse lines.

Purpose: The sweep imaging with Fourier transformation (SWIFT) imaging technique has been shown to provide positive contrast from diluted cell suspensions labeled with super-paramagnetic iron oxide (SPIO) in a tissue, as an alternative to T2*-weighted imaging. Here we demonstrate a variation of the SWIFT technique that yields a hyperintense signal from a concentrated cell suspension. The proposed technique provides minimal background signal from host tissue and facilitates visualization of injected cells., Methods: The proton resonance frequency and linewidth were determined for SPIO solutions of different concentrations. The original SWIFT sequence was modified and a dual saturation Gaussian shape RF pulse with ~200 Hz bandwidth was incorporated into the acquisition protocol to suppress host tissue and fat signals. This modification of the original acquisition protocol permits the detection of a hyperintense signal from grafted cells with minimal background signal from the host tissue., Results: SPIO particles not only induce broadening of NMR line-width but also an initiate proton resonance frequency shift. This shift is linearly proportional to the concentration of the iron oxide particles and induced by the bulk magnetic susceptibility of SPIOs. The shift of the resonance frequency of iron labeled cells allowed us effectively suppress the host tissues with saturation RF pulse to improve MRI detection of grafted cells., Conclusions: Iron oxide particles increase the resonance frequency of water proton signal. This shift permitted us to add the tissue/fat saturation RF pulse into the original SWIFT acquisition protocol and detect distinct hyperintense signals from grafted cells with minimal background signal from the host tissue., (© 2018 International Society for Magnetic Resonance in Medicine.)

Applications of multidimensional spatially-selective pulses are sometimes limited by their long pulse durations resulting from the need to execute a modulated gradient waveform in concert with RF transmission. Here, we introduce a method to design two-dimensional selective adiabatic pulses using a Cartesian k-space trajectory. The full pulse can be sampled using various undersampled segments to create a multidimensional pulse resilient to large off-resonances. Moreover, the pulse can be designed to be resilient to B 1 + inhomogeneity. Experimental demonstrations of fully segmented and single-shot k-space sampling patterns are presented., (Copyright © 2018 Elsevier Inc. All rights reserved.)

The first use of a surface coil to obtain a 31 P NMR spectrum from an intact rat by Ackerman and colleagues initiated a revolution in magnetic resonance imaging (MRI) and spectroscopy (MRS). Today, we take it for granted that one can detect signals in regions external to an RF coil; at the time, however, this concept was most unusual. In the approximately four decade long period since its introduction, this simple idea gave birth to an increasing number of innovations that has led to transformative changes in the way we collect data in an in vivo magnetic resonance experiment, particularly with MRI of humans. These innovations include spatial localization and/or encoding based on the non-uniform B 1 field generated by the surface coil, leading to new spectroscopic localization methods, image acceleration, and unique RF pulses that deal with B 1 inhomogeneities and even reduce power deposition. Without the surface coil, many of the major technological advances that define the extraordinary success of MRI in clinical diagnosis and in biomedical research, as exemplified by projects like the Human Connectome Project, would not have been possible., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Purpose: Iron-oxide nanoparticles (IONPs) have shown tremendous utility for enhancing image contrast and delivering targeted therapies. Quantification of IONPs has been demonstrated at low concentrations with gradient echo (GRE) and spin echo (SE), and at high concentrations with echoless sequences such as swept imaging with Fourier transform (SWIFT). This work examines the overlap of IONP quantification with GRE, SE, and SWIFT., Methods: The limit of quantification of GRE, SE, inversion-recovery GRE, and SWIFT sequences was assessed using IONPs at a concentration range of 0.02 to 89.29 mM suspended in 1% agarose. Empirically derived limits of quantification were compared with International Union of Pure and Applied Chemistry definitions. Both commercial and experimental IONPs were used., Results: All three IONPs assessed demonstrated an overlap of concentration quantification with GRE, SE, and SWIFT sequences. The largest dynamic range observed was 0.004 to 35.7 mM with Feraheme., Conclusions: The metrics established allow upper and lower quantitative limitations to be estimated given the relaxivity characteristics of the IONP and the concentration range of the material to be assessed. The methods outlined in this paper are applicable to any pulse sequence, IONP formulation, and field strength. Magn Reson Med 79:1420-1428, 2018. © 2017 International Society for Magnetic Resonance in Medicine., (© 2017 International Society for Magnetic Resonance in Medicine.)

Purpose: To introduce a method of designing single and parallel transmit (pTx) 3D adiabatic π pulses for inverting and refocusing spins that are insensitive to transmit B 1 ( B1+) inhomogeneity., Theory and Methods: A 3D adiabatic pulse is created by replacing each piece-wise constant element (or sub-pulse) of an adiabatic full passage (AFP) by a 2D selective pulse. In this study, the parent AFP is an HS1 and each sub-pulse is a 2D pulse derived from a jinc function designed using a spiral k-trajectory. Spatial selectivity in the third direction is achieved by blipping the slab-selective gradient between sub-pulses, yielding a rectangular slab profile identical to that of the parent AFP. The slew-rate limited sub-pulse can be undersampled utilizing pTx, thus shortening the overall pulse width. Simulations and experiments demonstrate the quality of spatial selectivity and adiabaticity achievable., Results: The 3D adiabatic pulse inverts and refocus spins in a sharply demarcated cylindrical volume. When stepping RF amplitude, an adiabatic threshold is observed above which the flip angle remains π. Experimental results demonstrate that pTx is an effective means to significantly improve pulse performance., Conclusion: A method of designing 3D adiabatic pulses insensitive to B 1 inhomogeneity has been developed. pTx can shorten these pulses while retaining their adiabatic character. Magn Reson Med 79:701-710, 2018. © 2017 International Society for Magnetic Resonance in Medicine., (© 2017 International Society for Magnetic Resonance in Medicine.)

Purpose: Conventional T 2 -weighted MRI produces a hypointense signal from iron-labeled cells, which renders quantification unfeasible. We tested a SWeep Imaging with Fourier Transformation (SWIFT) MRI pulse sequence to generate a quantifiable hyperintense signal from iron-labeled cells., Methods: Mesenchymal stem cells (MSCs) were labeled with different concentrations of iron oxide particles and examined for cell viability, proliferation, and differentiation. The SWIFT sequence was optimized to detect and quantify the amount of iron in the muscle tissue after injection of iron oxide solution and iron-labeled MSCs., Results: The incubation of MSCs with iron oxide and low concentration of poly-L-lysine mixture resulted in an internalization of up to 22 pg of iron per cell with no adverse effect on MSCs. Phantom experiments showed a dependence of SWIFT signal intensity on the excitation flip angle. The hyperintense signal from iron-labeled cells or solutions was detected, and an amount of the iron oxide in the tissue was quantified with the variable flip angle method., Conclusions: The SWIFT sequence can produce a quantifiable hyperintense MRI signal from iron-labeled cells. The graft of 18 x 10 6 cells was detectable for 19 days after injection and the amount of iron was quantifiable. The proposed protocol simplifies the detection and provides a means to quantify cell numbers. Magn Reson Med 78:1900-1910, 2017. © 2017 International Society for Magnetic Resonance in Medicine., (© 2017 International Society for Magnetic Resonance in Medicine.)

Recently introduced 3D radial MRI pulse sequence entitled Multi-Band SWeep Imaging with Fourier Transformation (MB-SWIFT) having virtually zero acquisition delay was used to obtain functional MRI (fMRI) contrast in rat's brain at 9.4 T during deep brain stimulation (DBS). The results demonstrate that MB-SWIFT allows functional images free of susceptibility artifacts, and provides an excellent fMRI activation contrast in the brain. Flip angle dependence of the MB-SWIFT fMRI signal and elimination of the fMRI contrast while using saturation bands, indicate a blood flow origin of the observed fMRI contrast. MB-SWIFT fMRI modality permits activation studies in the close proximity to an implanted lead, which is not possible to achieve with conventionally used gradient echo and spin echo - echo planar imaging fMRI techniques. We conclude that MB-SWIFT fMRI is a powerful imaging modality for investigations of functional responses during DBS., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: To use contrast based on longitudinal relaxation times (T 1 ) or rates (R 1 ) to quantify the biodistribution of iron oxide nanoparticles (IONPs), which are of interest for hyperthermia therapy, cell targeting, and drug delivery, within primary clearance organs., Methods: Mesoporous silica-coated IONPs (msIONPs) were intravenously injected into 15 naïve mice. Imaging and mapping of the longitudinal relaxation rate constant at 24 h or 1 week postinjection were performed with an echoless pulse sequence (SWIFT). Alternating magnetic field heating measurements were also performed on ex vivo tissues., Results: Signal enhancement from positive T 1 contrast caused by IONPs was observed and quantified in vivo in liver, spleen, and kidney at concentrations up to 3.2 mg Fe/(g tissue wt.) (61 mM Fe). In most cases, each organ had a linear correlation between the R 1 and the tissue iron concentration despite variations in intra-organ distribution, degradation, and IONP surface charge. Linear correlation between R 1 and volumetric SAR in hyperthermia therapy was observed., Conclusion: The linear dependence between R 1 and tissue iron concentration in major organs allows quantitative monitoring of IONP biodistribution in a dosage range relevant to magnetic hyperthermia applications, which falls into the concentration gap between CT and conventional MRI techniques. Magn Reson Med 78:702-712, 2017. © 2016 International Society for Magnetic Resonance in Medicine., (© 2016 International Society for Magnetic Resonance in Medicine.)