Project description: Magnetic Resonance Imaging of Transcranial Ultrasound Waves Background: Transcranial Ultrasound Stimulation (TUS) is an emerging non-invasive brain stimulation method that can achieve a highly focused stimulation also of deeper brain areas , an ability that sets it apart from the competing non-invasive techniques. The prospect of targeting deep brain regions non-invasively could greatly benefit the use of stimulation techniques in treatment of neuropsychiatric diseases. In contrast to High Intensity Focused Ultrasound (HIFU) where the objective is ablation, TUS operates at lower power ratings . Precise validation and control of dosage (i.e. strength and spatial distribution) of TUS is the most critical hurdle for its use in in-vivo human studies . Spatial distribution of the focal point is highly affected by the skull, and the tuning of ultrasound transducers can potentially overcome this problem, but only with sufficient feedback information . Magnetic resonance imaging can be made sensitive to the acoustic radiation forces created by TUS (termed MR-ARFI - Magnetic Resonance Acoustic Radiation Force Imaging). This technique was originally intended for the interrogation of the mechanical properties of tissues , but has more recently shown promise in imaging the small tissue displacement caused by different forms of focused ultrasound to the brain  hereunder TUS. In the future, MR imaging might be used to measure the ultrasound wave pattern in the human brain invivo, enabling an online targeting optimization and safety control during TUS. The development of complementary use of MR-ARFI and TUS is currently held back partly due to the low sensitivity of the former . Project goals and organization: In this project, we aspire to make MR-ARFI ready for its use it human in-vivo applications. To do so, this project will take a systematic approach to optimize the sensitivity to low ultrasound stimulation intensities - both for novel and established MR-ARFI sequences. The goal will be to enable MR-ARFI measurements of transcranial ultrasound waves at sonication parameters that are safe according to the FDA guidelines for diagnostic US. This encompasses acoustic intensities that are low enough to prevent inertial cavitation and a limitation of the US-induced heating to safe levels. To effectively narrow down the search for candidate sequences, we will firstly employ simulation-based investigations of well-established as well as novel MR-ARFI sequences. This will be followed by testing in a tissue-mimicking phantom for documenting the actual sensitivity of a small number selected candidate sequences. The sensitivity and spatial accuracy of the MR-ARFI of the candidate sequences will be quantified by comparison with hydrophone-based measurements of the acoustic wave distribution in a water tank and additionally with numerical simulations of the acoustic wave within the tissuemimicking phantom. The MR-ARFI measurements will be facilitated by the implementation of an inhouse setup for stereotactic navigation with an ultrasound transducer. The most promising sequences will be optimized further to minimize their sensitivity to subject movement and physiological noise due to heart beat and breathing, however, with the aim to maintain their sensitivity to the US waves. In the last part of the project, we aim to demonstrate the successful measurement of TUS waves in a proof-of-concept study on healthy participants. The project will be performed at DTU Health Tech and the Danish Research Centre for Magnetic Resonance (Copenhagen University Hospital Hvidovre). The theoretical and computational analyses of MR sequences will be performed predominantly at DTU. DRCMR will provide access to commercial software to simulate acoustic wave distributions inside the tissue-mimicking phantom and in human heads. In addition, it will provide access to the facilities (MR scanners, water tank setup) for the experimental tests. Project group: Principal supervisor: Axel Thielscher, Assoc. Prof., DTU Health Tech Co-supervisor: Lars G. Hanson, Assoc. Prof., DTU Health Tech Co-supervisor (DRCMR): Hartwig R. Siebner, Prof., University of Copenhagen PhD Student: Peter August Rasmussen Sources:  Bystritsky, A., Korb, A. S., Douglas, P. K., Cohen, M. S., Melega, W. P., Mulgaonkar, A. P., ... & Yoo, S. S. (2011). A review of low-intensity focused ultrasound pulsation. Brain stimulation, 4(3), 125-136.  Pasquinelli, C., Hanson, L. G., Siebner, H. R., Lee, H. J., & Thielscher, A. (2019). Safety of transcranial focused ultrasound stimulation: A systematic review of the state of knowledge from both human and animal studies. Brain stimulation, 12(6), 1367-1380.  Liu, H. L., McDannold, N., & Hynynen, K. (2005). Focal beam distortion and treatment planning in abdominal focused ultrasound surgery. Medical Physics, 32(5), 1270-1280.  Plewes, D. B., Betty, I., Urchuk, S. N., & Soutar, I. (1995). Visualizing tissue compliance with MR imaging. Journal of Magnetic Resonance Imaging, 5(6), 733-738.  McDannold, N., & Maier, S. E. (2008). Magnetic resonance acoustic radiation force imaging. Medical physics, 35(8), 3748-3758.