Real-Time Magnetic Resonance Imaging

Real‐time magnetic resonance imaging (RT‐MRI) allows for imaging dynamic processes as they occur, without relying on any repetition or synchronization. This is made possible by modern MRI technology such as fast‐switching gradients and parallel imaging. It is compatible with many (but not all) MRI sequences, including spoiled gradient echo, balanced steady‐state free precession, and single‐shot rapid acquisition with relaxation enhancement. RT‐MRI has earned an important role in both diagnostic imaging and image guidance of invasive procedures. Its unique diagnostic value is prominent in areas of the body that undergo substantial and often irregular motion, such as the heart, gastrointestinal system, upper airway vocal tract, and joints. Its value in interventional procedure guidance is prominent for procedures that require multiple forms of soft‐tissue contrast, as well as flow information. In this review, we discuss the history of RT‐MRI, fundamental tradeoffs, enabling technology, established applications, and current trends

ADVANCED INTRAVASCULAR MAGNETIC RESONANCE IMAGING WITH INTERACTION

Intravascular (IV) Magnetic Resonance Imaging (MRI) is a specialized class of interventional MRI (iMRI) techniques that acquire MRI images through blood vessels to guide, identify and/or treat pathologies inside the human body which are otherwise difficult to locate and treat precisely. Here, interactions based on real-time computations and feedback are explored to improve the accuracy and efficiency of IVMRI procedures. First, an IV MRI-guided high-intensity focused ultrasound (HIFU) ablation method is developed for targeting perivascular pathology with minimal injury to the vessel wall. To take advantage of real-time feedback, a software interface is developed for monitoring thermal dose with real-time MRI thermometry, and an MRI-guided ablation protocol developed and tested on muscle and liver tissue ex vivo. It is shown that, with cumulative thermal dose monitored with MRI thermometry, lesion location and dimensions can be estimated consistently, and desirable thermal lesions can be achieved in animals in vivo. Second, to achieve fully interactive IV MRI, high-resolution real-time 10 frames-per-second (fps) MRI endoscopy is developed as an advance over prior methods of MRI endoscopy. Intravascular transmit-receive MRI endoscopes are fabricated for highly under-sampled radial-projection MRI in a clinical 3Tesla MRI scanner. Iterative nonlinear reconstruction is accelerated using graphics processor units (GPU) to achieve true real-time endoscopy visualization at the scanner. The results of high-speed MRI endoscopy at 6-10 fps are consistent with fully-sampled MRI endoscopy and histology, with feasibility demonstrated in vivo in a large animal model. Last, a general framework for automatic imaging contrast tuning over MRI protocol parameters is explored. The framework reveals typical signal patterns over different protocol parameters from calibration imaging data and applies this knowledge to design efficient acquisition strategies and predicts contrasts under unacquired protocols. An external computer in real-time communication with the MRI console is utilized for online processing and controlling MRI acquisitions. This workflow enables machine learning for optimizing acquisition strategies in general, and provides a foundation for efficiently tuning MRI protocol parameters to perform interventional MRI in the highly varying and interactive environments commonly in play. This work is loosely inspired by prior research on extremely accelerated MRI relaxometry using the minimal-acquisition linear algebraic modeling (SLAM) method

Cardiovascular magnetic resonance guided electrophysiology studies

Catheter ablation is a first line treatment for many cardiac arrhythmias and is generally performed under x-ray fluoroscopy guidance. However, current techniques for ablating complex arrhythmias such as atrial fibrillation and ventricular tachycardia are associated with suboptimal success rates and prolonged radiation exposure. Pre-procedure 3D CMR has improved understanding of the anatomic basis of complex arrhythmias and is being used for planning and guidance of ablation procedures. A particular strength of CMR compared to other imaging modalities is the ability to visualize ablation lesions. Post-procedure CMR is now being applied to assess ablation lesion location and permanence with the goal of indentifying factors leading to procedure success and failure. In the future, intra-procedure real-time CMR, together with the ability to image complex 3-D arrhythmogenic anatomy and target additional ablation to regions of incomplete lesion formation, may allow for more successful treatment of even complex arrhythmias without exposure to ionizing radiation. Development of clinical grade CMR compatible electrophysiology devices is required to transition intra-procedure CMR from pre-clinical studies to more routine use in patients

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

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