1. ULTRAFAST BRAIN MR IMAGING: CURRENT AND EMERGING TECHNIQUES Abstract #eEdE-96 Submission #1907 Rapalino O 1, Pinto J 2, Prakkamakul S 3, Witzel T 4, Heberlein K 5, Van-der-Kouwe A 4, Ratai E 4, Rosen B 4, Gonzalez G 1, Schaefer P 1. 1 : Neuroradiology Division, Massachusetts General Hospital, Boston, MA, 2 : CDPI, Rio de Janeiro, Brazil, 3 : King Chulalongkorn Memorial Hospital Thai Red Cross Society, Bangkok, Thailand 4 : Athinoula A. Martinos Center for Biomedical Imaging, Charlestown, MA, 5 : Siemens Medical Solutions, Charlestown, MA

2. DISCLAIMERS Joana Pinto, MD – Research Fellow Siemens Medical Solutions Keith Heberlein, PhD – Full time employee, Sr Mgr Engineering Siemens Medical Solutions Remaining authors have no disclosures ULTRAFAST BRAIN MR IMAGING: Current and Emerging Techniques

3. To describe practical protocols for fast and ultrafast brain magnetic resonance imaging (MRI) using commercially available sequences. To provide a general overview of new sequences and techniques that could further accelerate MRI acquisitions. PURPOSE ULTRAFAST BRAIN MR IMAGING: Current and Emerging Techniques

4. Optimized MRI protocols for ultrafast brain MR imaging were compiled for different commercially available scanners to provide a practical framework for patients who cannot tolerate long MRI acquisition times, including pediatric cases and patients with altered mental status. Current state-of-the-art MR sequences and promising emerging techniques for ultrafast brain imaging are discussed, including brief descriptions of their physical principles and potential clinical applications. METHODS ULTRAFAST BRAIN MR IMAGING: Current and Emerging Techniques

5. The combination of parallel imaging, multichannel head coils and optimized MR sequences can result in ultrafast brain MR protocols that can be used for: imaging of unstable, critically ill and/or motion-prone patients; performing dynamic or real time MR imaging; to accelerate the acquisition of basic MR protocols. Common commercially available sequences can be optimized to eliminate unnecessary acquisition and processing steps to accelerate routine MR protocols. DISCUSSION ULTRAFAST BRAIN MR IMAGING: Current and Emerging Techniques

6. Content organization: Introduction Importance of rapid clinical imaging History and background of rapid clinical imaging Clinical scenarios for use Current status of fast MRI Currently available fast MRI sequences Fast MRI methods Hardware for fast MRI Developing and future techniques Ultrafast MRI sequences Hardware for ultrafast MRI DISCUSSION ULTRAFAST BRAIN MR IMAGING: Current and Emerging Techniques

7. INTRODUCTION ULTRAFAST BRAIN MR IMAGING: Current and Emerging Techniques

8.  Importance of rapid clinical imaging Long scan times are almost always uncomfortable for patients and introduce the potential for patient motion, causing artifacts. Rapid clinical imaging aids imaging structures that move, such as the heart, or in which contrast changes over time (arterial studies). MRI is under utilized in clinical care. Limited population for whom MRI is available - pediatric patients, patients with claustrophobia and patients with involuntary movements. ULTRAFAST BRAIN MR IMAGING: Current and Emerging Techniques

9. 1970 Hardware: MR Gradients 2016 Strong Gradients capable of rapid switching 1980’s Acquisition: MR pulse sequences Ultrafast SE/GE EPI Spiral … 1990’s Parallelism: RF Coils Many points of data at once Multi RF detectors = RF coils 2000’s Sparsity  Evolution of rapid clinical MR imaging Compressed Sensing

10.  Background of rapid clinical imaging Three basic key components involved in the process of image formation in conventional MRI: Pulse sequence – dictates scanner activities (turning on and off the magnetic field gradients, playing out radiofrequency (RF) excitation pulses, switching on the receivers to acquire the signals) K-space - K-space is the data matrix in which the acquired data are arranged Reconstruction- mathematical process responsible for converting the data acquired into a magnetic resonance (MR) image ULTRAFAST BRAIN MR IMAGING: Current and Emerging Techniques

11.  Background of rapid clinical imaging There are two major mechanisms used to reduce scan time: Nº of RF excitations needed to fill the k-space Repetition time (TR) * One RF pulse acquires several lines of k-space – Single Shot Sequences. * Segmented acquisition of the k-space ULTRAFAST BRAIN MR IMAGING: Current and Emerging Techniques

12. Ultrafast imaging limitations: Decreased spatial resolution Blurring Geometric distortion Less image contrast signal-to-noise ratio Radiofrequency power deposition Risk for peripheral nerve stimulation  Background of rapid clinical imaging ULTRAFAST BRAIN MR IMAGING: Current and Emerging Techniques

13.  Background of rapid clinical imaging Image Speed Total time to acquire data Readouts per shot Switching speed of stronger gradients SNR Susceptibility to signal evolution Susceptibility to experimental imperfection - Better actively shielded gradients - Pre-scan/calibration - Account for variation in reconstruction -Frequency-selective excitation or saturation -Shimming -Small matrix size -Multishot or PI -Account for variation in reconstruction -Higher field strength -Contrast agents -Signal average -Improved coils -Shorter echo time -Optimize pulse sequence

14.  Clinical scenarios for use General overview: Abbreviating the total scan time. * Fit data acquisition within a breathhold * Enable large volume coverage * Increase spatial and temporal resolution Freezing physiological motion or capturing dynamic events in real time. Practical applications in brain imaging: Reduction in total scan time for routine brain MRI Evaluation of children with hydrocephalus Decrease movement artifacts in pediatric brain imaging Functional MRI (BOLD) Perfusion MRI (ASL / first-pass tracing) Diffusion imaging ULTRAFAST BRAIN MR IMAGING: Current and Emerging Techniques

15. CURRENT STATUS ULTRAFAST BRAIN MR IMAGING: Current and Emerging Techniques

16.  Currently available fast MR sequences Spin Echo Sequences (SE) Fast SE (FSE), Turbo SE (TSE) ULTRAFAST BRAIN MR IMAGING: Current and Emerging Techniques Ultrafast SE

17.  Currently available fast MR sequences Ultrafast SE Sequences ⌘ axial acquisition – 27 slices – 3T scanner (skyra) (FSE = 2:26 sec) *Half-Fourier Acquisition Single-shot Turbo spin Echo **Ultra Fast Spin Echo ***Fast Advanced Spin Echo ULTRAFAST BRAIN MR IMAGING: Current and Emerging Techniques

18.  Currently available fast MR sequences Gradient Echo Sequences (GE) Fast Gradient Echo Spoiled GE (RF spoiling / Gradient Spoiling) ULTRAFAST BRAIN MR IMAGING: Current and Emerging Techniques Ultrafast Spoiled GE

19. Ultrafast Spoiled GE sequences ⌘ axial acquisition – 25 slices – 3T scanner (skyra) *Fast Spoiled Gradient Echo **Inversion Recovery Fast Spoiled Gradient Echo ***Fast Low Angle Shot ****Turbo Field Echo *****Fast Field Echo  Currently available fast MR sequences ULTRAFAST BRAIN MR IMAGING: Current and Emerging Techniques

20.  Currently available fast MR sequences Ultrafast Spoiled GE 3D sequences ⌘ 3T scanner (skyra) ULTRAFAST BRAIN MR IMAGING: Current and Emerging Techniques

21. Echo Planar Imaging Sequences (EPI) Spin echo EPI Gradient echo EPI  Currently available fast MR sequences ULTRAFAST BRAIN MR IMAGING: Current and Emerging Techniques

22.  Currently available fast MR sequences ULTRAFAST BRAIN MR IMAGING: Current and Emerging Techniques

23.  Currently available fast MR sequences Echo Planar Imaging Applications Diffusion Weighted Imaging (DWI) Intra Voxel Incoherent Motion (IVIM) Diffusion Tensor Imaging (DTI) BOLD Functional MRI (fMRI) Perfusion Weighted Imaging (PWI) Dynamic Susceptibility Contrast (DSC) Arterial Spin Labeling (ASL) Magnetic Resonance Spectroscopic Imaging (MRSI) Applications that take a significant amount of time to achieve the image contrast or that need to wait for the right moment to image benefit from ultrafast sequences ULTRAFAST BRAIN MR IMAGING: Current and Emerging Techniques

24.  Currently available fast MR sequences Echo Planar Imaging Applications Diffusion Weighted Imaging (DWI) Intra Voxel Incoherent Motion (IVIM) Diffusion Tensor Imaging (DTI) The Stejskal-Tanner diffusion-sensitizing module of the pulse sequence takes considerable time to reach a sufficiently high b factor. Using single-shot EPI, each image can be acquired within the time frame of 0.1 second. With the recent introduction of parallel imaging, the quality of EPI scans has been significantly improved. The accelerated k-space traversal in parallel imaging results in reduced blurring and geometric distortions caused by off-resonant spins. ULTRAFAST BRAIN MR IMAGING: Current and Emerging Techniques

25.  Currently available fast MR sequences Echo Planar Imaging Applications BOLD Functional MRI (fMRI) To generate a high blood-oxygenation-level-dependent (BOLD) contrast to detect the hemodynamic response it is necessary to have a long echo time, but this also reduces the scan efficiency. Therefore, BOLD imaging benefit from EPI sequences in order to achieve whole-head coverage and to maximize the data acquisition per repetition. ULTRAFAST BRAIN MR IMAGING: Current and Emerging Techniques

26. Echo Planar Imaging Applications Perfusion Weighted Imaging (PWI) Dynamic Susceptibility Contrast (DSC) Arterial Spin Labeling (ASL) The two main concepts for PWI are the labeling of arterial blood, also know as arterial spin labeling (ASL), and the first-pass tracing of the contrast agent, which in human brain happens after about 15 seconds, demanding ultrafast imaging. ASL is used for quantitative measurements in perfusion and due to both the waiting time required for the transit of blood and the desire for large brain volume coverage the application of an ultrafast sequence is also of great value to circumvent this technical time-problem, otherwise responsible for making this technique not viable for practical use.  Currently available fast MR sequences ULTRAFAST BRAIN MR IMAGING: Current and Emerging Techniques

27. Parallel imaging (PI) Efficient scan techniques that uses multiple independent receiver coils, which allows that a high percentage of the scan time is used for data acquisition.  PI techniques don’t represent new imaging sequences.  PI serves to accelerate any imaging sequence that already exists in clinical use (e.g., gradient echo, spin echo, echo planar imaging).  PI doesn’t necessarily have an affect on the contrast of the underlying pulse sequence.  PI techniques can be applied (i) to speed up the image acquisition, (ii) to increase the spatial resolution in a given time, or (iii) a association of both.  Fast MR Methods ULTRAFAST BRAIN MR IMAGING: Current and Emerging Techniques

28. SMASH – Simultaneous Acquisition of Spatial Harmonics SENSE – Sensitivity Encoding GRAPPA – Generalized Auto calibrating Partially Parallel Acquisitions CAIPIRINHA - Controled Aliasing in Parallel Imaging Results in Higher Acceleration  Fast MR Methods ULTRAFAST BRAIN MR IMAGING: Current and Emerging Techniques

29. 32 channel head coils 64 channel head coils Coils compatible with parallel imaging for fast high-resolution and advanced neuroimaging. Brain studies benefit from RF receive-coil arrays of up to 64 channel.  Hardware for fast MRI ULTRAFAST BRAIN MR IMAGING: Current and Emerging Techniques

30. DEVELOPING AND FUTURE TECHNIQUES ULTRAFAST BRAIN MR IMAGING: Current and Emerging Techniques

31. Compressed Sensing (CS) Magnetic Resonance Fingerprinting (MRF) Simultaneous Multi-slice (SMS) Echo Planar Imaging Spiral GRAPPA Spatiotemporally encoded (SPEN) Single shot  Sequences for ultrafast MR imaging ULTRAFAST BRAIN MR IMAGING: Current and Emerging Techniques

32.  Sequences for ultrafast MR imaging Compressed Sensing (CS) Natural images can often be compressed with little or no perceptible loss of information. Transform-based compression is a widely used strategy adopted in the JPEG, JPEG-2000, and MPEG standards. The MRI CS is founded on the premise of reconstructing an image from an incompletely filled k- space. It measures a small number of random linear combinations of the signal values much smaller than the number of signal samples nominally defining it. In MRI the sampled linear combinations are simply individual Fourier coefficients (k-space samples). Makes accurate reconstructions from a small subset of k-space rather than an entire k-space grid. ULTRAFAST BRAIN MR IMAGING: Current and Emerging Techniques

33. Compressed Sensing (CS) The CS approach requires: (a) Transform sparsity: the desired image have a sparse representation in a known transform domain (b) Incoherence of undersampling artifacts: the aliasing artifacts due to k-space undersampling should be incoherent (noise like) in the sparsifying transform domain (c) Nonlinear reconstruction: a nonlinear reconstruction should be used to enforce both sparsity of the image representation and consistency with the acquired data.  Sequences for ultrafast MR imaging (a)(b) Thresholding Data consistency (c) ULTRAFAST BRAIN MR IMAGING: Current and Emerging Techniques

34. Compressed Sensing (CS) Different CS techniques: (1) k-t FOCUSS - k-t space FOCal underdetermined system solver. (2) k-t BLAST - k-t broad-use linear acquisition speed-up technique (3) k-t FOCUSS for Dynamic MR (4) Bayesian Experimental Design (5) Modified CS (6) Motion-Compensated Modified CS (MC-MCS) Combination of CS and PI: maximum acceleration  Sequences for ultrafast MR imaging ULTRAFAST BRAIN MR IMAGING: Current and Emerging Techniques

35.  Sequences for ultrafast MR imaging Magnetic Resonance Fingerprinting (MRF) A new and recent approach to data acquisition, post-processing and visualization. Permits the simultaneous non-invasive quantification of multiple important properties of a material or tissue. Related to the concept of compressed sensing. Allows fast and simultaneous acquisition of quantitative tissue parameters. Pursues unique signal evolutions, using pseudorandomized acquisition, that are sensitive to multiple parameters for different materials or tissue type (unique signal evolution = “fingerprint”). MRF can quantify these parameters by comparing the acquired signal pattern to a dictionary of presimulated fingerprints Ma D, et al 2013 ULTRAFAST BRAIN MR IMAGING: Current and Emerging Techniques

36. Magnetic Resonance Fingerprinting (MRF) Inversion recovery based steady-state free precession sequence. Signal readout fast sampling trajectory based on variable density spiral readout. Spatial undersampling speed-up measurement times. Pseudorandomized acquisition of parameters - Flip Angle (FA), TR, TE, phase of RF pulses and readout trajectory Fingerprints  Sequences for ultrafast MR imaging ULTRAFAST BRAIN MR IMAGING: Current and Emerging Techniques

37. Simultaneous Multi-slice (SMS) Echo Planar Imaging Simultaneous multi-slice (SMS) pulse sequence applies a multiband (MB) composite RF pulse with slice-selective gradient to simultaneously excite multiple slice planes.  Sequences for ultrafast MR imaging ULTRAFAST BRAIN MR IMAGING: Current and Emerging Techniques

38. Spiral GRAPPA Spiral trajectories is an efficient way to cover a desired k-space partition, but they are more susceptible to off-resonance effects that cause blurring artifacts. Off-resonance effects scale with the readout duration, the respective artifacts can be reduced by shortening the readout trajectory. Parallel imaging methods improve image quality through an increase in the acquisition speed. Technique that combines parallel imaging reconstruction (GRAPPA) and spiral k-space coverage. Allows the use of fewer spiral segments, improving imaging speed and lessening required gradient performance. The computation time for spiral GRAPPA is on the order of the duration needed to grid a single image, hence the benefits of using k-space based reconstruction include faster reconstruction time and availability of single coil images.  Sequences for ultrafast MR imaging Solid line ( ) – acquired k-space lines Dashed line ( ) – reconstructed k-space lines ULTRAFAST BRAIN MR IMAGING: Current and Emerging Techniques

39. Spatiotemporally encoded (SPEN) Single shot This encoding approach relies on applying a frequency-swept radio- frequency (chirped RF) excitation pulse in the presence of a magnetic field gradient, which acts to spread out the effective resonance frequencies of the spins throughout the region of interest (ROI). Acquisition of the spins’ response in the presence of a second field gradient then produces a signal S(t), which, at each instant in time, is directly proportional to the spin density profile at consecutive points along the encoded axis No Fourier transform (FT) needs to be involved in the data processing procedure Provide much higher robustness to magnetic field in homogeneities as compared to EPI. One of the essential differences between k-space and SPEN relates to the fact that, whereas the former method encodes the image during the acquisition stage, SPEN encoding is performed during the excitation. SPEN applications: diffusion, functional MRI, perfusion imaging and chemical shift spectroscopic imaging studies.  Sequences for ultrafast MR imaging ULTRAFAST BRAIN MR IMAGING: Current and Emerging Techniques

40.  Sequences for ultrafast MR imaging Spatiotemporally encoded (SPEN) Single shot Application of a frequency-swept radio-frequency (chirped RF) excitation pulse in the presence of a magnetic field gradient. ULTRAFAST BRAIN MR IMAGING: Current and Emerging Techniques

41. 64 channel head coil 96 channel head coil – not yet clinically available ”Theoretically as the number of receive-arrays channel increases it is possible to reduce the size of individual elements and achieve increasing SNR gains, without losing sensitivity further from the coils, in addition to improved encoding acceleration performance."  Hardware for fast MRI ULTRAFAST BRAIN MR IMAGING: Current and Emerging Techniques

42.  The proper use of multichannel head coils, parallel imaging and careful optimization of commercially available MR sequences can significantly accelerate most clinical MR protocols.  There are several MR technologies in the pre-clinical development pipeline that promise further reduction of acquisition times with similar or higher diagnostic accuracy. CONCLUSION ULTRAFAST BRAIN MR IMAGING: Current and Emerging Techniques

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