A novel receive-only liquid nitrogen (LN2)-cooled RF coil for high-resolution in vivo imaging on a 3-Tesla whole-body scanner

The design and operation of a receive-only liquid nitrogen (LN2)-cooled coil and cryostat suitable for medical imaging on a 3-T whole-body magnetic resonance scanner is presented. The coil size, optimized for murine imaging, was determined by using electromagnetic (EM) simulations. This process is therefore easier and more cost effective than building a range of coils. A nonmagnetic cryostat suitable for small-animal imaging was developed having good vacuum and cryogenic temperature performance. The LN2-cooled probe had an active detuning circuit allowing the use with the scanner's built-in body coil. External tuning and matching was adopted to allow for changes to the coil due to temperature and loading. The performance of the probe was evaluated by comparison of signal-to-noise ratio (SNR) with the same radio-frequency RF) coil operating at room temperature (RT). The performance of the RF coil at RT was also benchmarked against a commercial surface coil with a similar dimension to ensure a fair SNR comparison. The cryogenic coil achieved a 1.6- to twofold SNR gain for several different medical imaging applications: For mouse-brain imaging, a 100-mu m resolution was achieved in an imaging time of 3.5 min with an SNR of 25-40, revealing fine anatomical details unseen at lower resolutions for the same time. For heavier loading conditions, such as imaging of the hind legs and liver, the SNR enhancement was slightly reduced to 1.6-fold. The observed SNR was in good agreement with the expected SNR gain correlated with the loaded-quality factor of RF coils from the EM simulations. With the aid of this end-user-friendly and economically attractive cryogenic RF coil, the enhanced SNR available can be used to improve resolution or reduce the duration of individual scans in a number of biomedical applications

Accelerated MRI at 9.4 T with electronically modulated time-varying receive sensitivities

PURPOSE To investigate how electronically modulated time-varying receive sensitivities can improve parallel imaging reconstruction at ultra-high field. METHODS Receive sensitivity modulation was achieved by introducing PIN diodes in the receive loops, which allow rapid switching of capacitances in both arms of each loop coil and by that alter B$_{1}$ $^{-}$ profiles, resulting in two distinct receive sensitivity configurations. A prototype 8-channel reconfigurable receive coil for human head imaging at 9.4T was built, and MR measurements were performed in both phantom and human subject. A modified SENSE reconstruction for time-varying sensitivities was formulated, and g-factor calculations were performed to investigate how modulation of receive sensitivity profiles during image encoding can improve parallel imaging reconstruction. The optimized modulation pattern was realized experimentally, and reconstructions with the time-varying sensitivities were compared with conventional static SENSE reconstructions. RESULTS The g-factor calculations showed that fast modulation of receive sensitivities in the order of the ADC dwell time during k-space acquisition can improve parallel imaging performance, as this effectively makes spatial information of both configurations simultaneously available for image encoding. This was confirmed by in vivo measurements, for which lower reconstruction errors (SSIM = 0.81 for acceleration R = 4) and g-factors (max g = 2.4; R = 4) were observed for the case of rapidly switched sensitivities compared to conventional reconstruction with static sensitivities (SSIM = 0.74 and max g = 3.2; R = 4). As the method relies on the short RF wavelength at ultra-high field, it does not yield significant benefits at 3T and below. CONCLUSIONS Time-varying receive sensitivities can be achieved by inserting PIN diodes in the receive loop coils, which allow modulation of B$_{1}$ $^{-}$ patterns. This offers an additional degree of freedom for image encoding, with the potential for improved parallel imaging performance at ultra-high field

Functional MRI of Rehabilitation in Chronic Stroke Patients Using Novel MR-Compatible Hand Robots

We monitored brain activation after chronic stroke by combining functional magnetic resonance imaging (fMRI) with a novel MR-compatible, hand-induced, robotic device (MR_CHIROD). We evaluated 60 fMRI datasets on a 3 T MR system from five right-handed patients with left-sided stroke ≥6 months prior and mild to moderate hemiparesis. Patients trained the paretic right hand at approximately 75% of maximum strength with an exercise ball for 1 hour/day, 3 days/week for 4 weeks. Multi-level fMRI data were acquired before, during training, upon completion of training, and after a non-training period using parallel imaging employing GeneRalized Autocalibrating Partially Parallel Acquisitions (GRAPPA) while the participant used the MR_CHIROD. Training increased the number of activated sensorimotor cortical voxels, indicating functional cortical plasticity in chronic stroke patients. The effect persisted four weeks after training completion, indicating the potential of rehabilitation in inducing cortical plasticity in chronic stroke patients

A study on the change in plasma membrane potential during sonoporation

Posters: no. 4Control ID: 1680329OBJECTIVES: There has been validated that the correlation of sonoporation with calcium transients is generated by ultrasound-mediated microbubbles activity. Besides calcium, other ionic flows are likely involved in sonoporation. Our hypothesis is the cell electrophysiological properties are related to the intracellular delivery by ultrasound and microbubbles. In this study, a real-time live cell imaging platform is used to determine whether plasma membrane potential change is related to the sonoporation process at the cellular level. METHODS: Hela cells were cultured in DMEM supplemented with 10% FBS in Opticell Chamber at 37 °C and 5% CO2, and reached 80% confluency before experiments. The Calcein Blue-AM, DiBAC4(3) loaded cells in the Opticell chamber filled with PI solution and Sonovue microbubbles were immerged in a water tank on a inverted fluorescence microscope. Pulsed ultrasound (1MHz freq., 20 cycles, 20Hz PRF, 0.2-0.5MPa PNP) was irradiated at the angle of 45° to the region of interest for 1s.The real-time fluorescence imaging for different probes was acquired by a cooled CCD camera every 20s for 10min. The time-lapse fluorescence images were quantitatively analyzed to evaluate the correlation of cell viability, intracellular delivery with plasma membrane potential change. RESULTS: Our preliminary data showed that the PI fluorescence, which indicated intracellular delivery, was immediately accumulated in cells adjacent to microbubbles after exposure, suggesting that their membranes were damaged by ultrasound-activated microbubbles. However, the fluorescence reached its highest level within 4 to 6 minutes and was unchanged thereafter, indicating the membrane was gradually repaired within this period. Furthermore, using DIBAC4(3), which detected the change in the cell membrane potential, we found that the loss of membrane potential might be associated with intracellular delivery, because the PI fluorescence accumulation was usually accompanied with the change in DIBAC4 (3) fluorescence. CONCLUSIONS: Our study suggests that there may be a linkage between the cell membrane potential change and intracellular delivery mediated by ultrasound and microbubbles. We also suggest that other ionic flows or ion channels may be involved in the cell membrane potential change in sonoporation. Further efforts to explore the cellular mechanism of this phenomenon will improve our understanding of sonoporation.postprin

Developmental delays and subcellular stress as downstream effects of sonoporation

Posters: no. 2Control ID: 1672434OBJECTIVES: The biological impact of sonoporation has often been overlooked. Here we seek to obtain insight into the cytotoxic impact of sonoporation by gaining new perspectives on anti-proliferative characteristics that may emerge within sonoporated cells. We particularly focused on investigating the cell-cycle progression kinetics of sonoporated cells and identifying organelles that may be stressed in the recovery process. METHODS: In line with recommendations on exposure hardware design, an immersion-based ultrasound platform has been developed. It delivers 1 MHz ultrasound pulses (100 cycles; 1 kHz PRF; 60 s total duration) with 0.45 MPa peak negative pressure to a cell chamber that housed HL-60 leukemia cells and lipid-shelled microbubbles at a 10:1 cell-tobubble ratio (for 1e6/ml cell density). Calcein was used to facilitate tracking of sonoporated cells with enhanced uptake of exogenous molecules. The developmental trend of sonoporated cells was quantitatively analyzed using BrdU/DNA flow cytometry that monitors the cell population’s DNA synthesis kinetics. This allowed us to measure the temporal progression of DNA synthesis of sonoporated cells. To investigate whether sonoporation would upset subcellular homeostasis, post-exposure cell samples were also assayed for various proteins using Western blot analysis. Analysis focus was placed on the endoplasmic reticulum (ER): an important organelle with multi-faceted role in cellular functioning. The post-exposure observation time spanned between 0-24 h. RESULTS: Despite maintaining viability, sonoporated cells were found to exhibit delays in cell-cycle progression. Specifically, their DNA synthesis time was lengthened substantially (for HL-60 cells: 8.7 h for control vs 13.4 h for the sonoporated group). This indicates that sonoporated cells were under stress: a phenomenon that is supported by our Western blot assays showing upregulation of ER-resident enzymes (PDI, Ero1), ER stress sensors (PERK, IRE1), and ER-triggered pro-apoptotic signals (CHOP, JNK). CONCLUSIONS: Sonoporation, whilst being able to facilitate internalization of exogenous molecules, may inadvertently elicit a cellular stress response. These findings seem to echo recent calls for reconsideration of efficiency issues in sonoporation-mediated drug delivery. Further efforts would be necessary to improve the efficiency of sonoporation-based biomedical applications where cell death is not desirable.postprin