Vitrification, a kinetic process of liquid solidification into glass, poses many potential benefits for tissue cryopreservation including indefinite storage, banking, and facilitation of tissue ...matching for transplantation. To date, however, successful rewarming of tissues vitrified in VS55, a cryoprotectant solution, can only be achieved by convective warming of small volumes on the order of 1 ml. Successful rewarming requires both uniform and fast rates to reduce thermal mechanical stress and cracks, and to prevent rewarming phase crystallization. We present a scalable nanowarming technology for 1- to 80-ml samples using radiofrequency-excited mesoporous silica-coated iron oxide nanoparticles in VS55. Advanced imaging including sweep imaging with Fourier transform and microcomputed tomography was used to verify loading and unloading of VS55 and nanoparticles and successful vitrification of porcine arteries. Nanowarming was then used to demonstrate uniform and rapid rewarming at >130°C/min in both physical (1 to 80 ml) and biological systems including human dermal fibroblast cells, porcine arteries and porcine aortic heart valve leaflet tissues (1 to 50 ml). Nanowarming yielded viability that matched control and/or exceeded gold standard convective warming in 1- to 50-ml systems, and improved viability compared to slow-warmed (crystallized) samples. Last, biomechanical testing displayed no significant biomechanical property changes in blood vessel length or elastic modulus after nanowarming compared to untreated fresh control porcine arteries. In aggregate, these results demonstrate new physical and biological evidence that nanowarming can improve the outcome of vitrified cryogenic storage of tissues in larger sample volumes.
Frequency-modulated (FM) pulses that function according to adiabatic principles are becoming increasingly popular in many areas of NMR. Often adiabatic pulses can extend experimental capabilities and ...minimize annoying experimental imperfections. Here, adiabatic principles and some of the current methods used to create these pulses are considered. The classical adiabatic rapid passage, which is a fundamental element upon which all adiabatic pulses and sequences are based, is analyzed using vector models in different rotating frames of reference. Two methods to optimize adiabaticity are described, and ways to tailor modulation functions to best satisfy specific experimental needs are demonstrated. Finally, adiabatic plane rotation pulses and frequency-selective multiple spin-echo sequences are considered.
The Human Connectome Project (HCP) relies primarily on three complementary magnetic resonance (MR) methods. These are: 1) resting state functional MR imaging (rfMRI) which uses correlations in the ...temporal fluctuations in an fMRI time series to deduce ‘functional connectivity’; 2) diffusion imaging (dMRI), which provides the input for tractography algorithms used for the reconstruction of the complex axonal fiber architecture; and 3) task based fMRI (tfMRI), which is employed to identify functional parcellation in the human brain in order to assist analyses of data obtained with the first two methods. We describe technical improvements and optimization of these methods as well as instrumental choices that impact speed of acquisition of fMRI and dMRI images at 3T, leading to whole brain coverage with 2mm isotropic resolution in 0.7s for fMRI, and 1.25mm isotropic resolution dMRI data for tractography analysis with three-fold reduction in total dMRI data acquisition time. Ongoing technical developments and optimization for acquisition of similar data at 7T magnetic field are also presented, targeting higher spatial resolution, enhanced specificity of functional imaging signals, mitigation of the inhomogeneous radio frequency (RF) fields, and reduced power deposition. Results demonstrate that overall, these approaches represent a significant advance in MR imaging of the human brain to investigate brain function and structure.
•We describe technical advances accomplished in the Human Connectome Project (HCP).•Highly accelerated imaging significantly improves fMRI and diffusion weighted MRI.•Instrumentation improvements in the HCP lead to superior diffusion-weighted MRI.•We describe of HCP efforts at both 3 and 7T, comparing their relative merits.•We describe recent developments with RF pulses for improved slice accelerated MRI.
•Smaller, more affordable, and more portable MRI scanners offer opportunities to address unmet research needs and long-standing health inequities in remote and resource-limited international ...settings.•However, the use of portable MRI in field-based settings raises challenging ethical, legal, and social issues (ELSI) that have not been adequately examined.•A guiding principle for field-based MRI research must be ensuring that local communities are ongoing partners in the co-creation of knowledge.•Field-based MRI research in remote, low-resource settings should produce local value to justify the risks of the research and minimize the possibility of abuse.•More opportunities for genuine bi-directional learning are needed to address these issues, and development of consensus guidance should prioritize participation of stakeholders from resource-limited communities.
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.
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.
•MB-SWIFT is significantly quieter than EPI, and insensitive to body movement.•Almost whole-brain functional parcellation was achieved in awake rats with MB-SWIFT.•EEG and MB-SWIFT fMRI signals had excellent correlation in anesthetized rats.•Gradient artefacts in EEG-fMRI recordings were only minimal during MB-SWIFT.•MB-SWIFT is a robust fMRI method that can overcome many of the drawbacks of EPI.
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.
•MB-SWIFT fMRI allows imaging of head-fixed spontaneously behaving rats.•Anatomically relevant functional parcellation was obtained.•Brain activity in relevant networks during spontaneous behavior ...was measured.•Applied methodology enables novel behavioral study designs in rodents.
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.
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.
Nanowarming is a new technology that could solve the technical challenge of volumetric rewarming of cryopreserved biological samples. With the aim of scaling up nanowarming technology from cell and simple tissues to a whole organ, a scalable silica‐coated iron oxide nanoparticle is synthesized and tested for cell nanowarming and organ perfusional loading and removal.
Vitrification and Nanowarming of Kidneys Sharma, Anirudh; Rao, Joseph Sushil; Han, Zonghu ...
Advanced science,
10/2021, Letnik:
8, Številka:
19
Journal Article
Recenzirano
Odprti dostop
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.
Vitrification dramatically increases organ storage times in the cryogenic state beyond current storage limits. However, vitrified kidneys cannot currently be rewarmed sufficiently rapidly or uniformly to avoid ice crystallization or cracking failures. A new radiofrequency rewarming technology called “nanowarming” addresses this problem by exciting magnetic nanoparticles to rewarm vitrified kidneys rapidly and uniformly.
PDF
