Understanding tissue mechanics, architecture and function using a gravitational magnetic resonance elastography transducer.

We are applying for registration of a trial using an investigational medical device that is not currently registered on the Australian Register of Therapeutic Goods (ARTG). The device in question is referred to as the gravitational magnetic resonance (MR) elastography transducer. Put simply, MR elastography is an MR imaging technology that uses the way that shear vibrations travel through in-vivo tissues (as imaged using an MR scanner) to provide information about tissue mechanical properties. The transducer produces a vibration that feels similar to an electric toothbrush through the rotation of an eccentric mass. The device is placed externally on the body of participants and is used to vibrate various body regions during MR scanning. In this study, the device will be used as a means of producing painless shear wave vibrations in the target tissues of participants undergoing MR scanning. The scanning will take place during a single visit to the Imaging Facility at NeuRA, in Randwick NSW 2031. Participants will undergo MR scanning of their brain, abdomen, spinal cord, adipose tissue or skeletal muscle. During MR imaging, we will obtain images of: - Tissue anatomy (T1 and T2 weighted imaging); - Anisotropy (diffusion tensor imaging, DTI); - Fat content (DIXON imaging); - Real-time phase-contrast imaging of shear wave propagation (MR elastography); - Real-time tissue strain during deformation (tagged MR). If the tissue is able to be deformed by compression, joint rotation or active isometric contraction, the scans will be repeated while undergoing that deformation. Post-processing of these scans will allow various anatomical measurements and the large deformation, anisotropic mechanical properties of the tissue to be reconstructed. The reconstructed data will be quantitatively analysed using statistical methods to obtain group mechanical property data for the tissues, and how they vary during deformation. Participants will be required to undergo MR scanning of – depending on the tissue being investigated – either their: i. Head/neck (brain, tongue, spinal cord); ii. Buttocks (adipose tissue); iii. Abdomen (liver/kidney); iv. Upper or lower extremity (skeletal muscle/tendon). The participant will be asked to lie down on a comfortable padded table that goes inside the large tube that is the imaging magnet. They will have a series of pictures taken of their body using the MRI scanner. While measurements of elasticity are being recorded, vibration will be transmitted into the tissue being investigated via a purpose built device, comprising a gravitational design that produces vibration through the rotation of an eccentric mass. Vibration will be transmitted directly to the participant by placing the device directly over or on the tissue of interest. If the transducer is to be positioned over bone, a gel pad will be placed between the transducer and the participant for comfort. We may also apply some compression to the body area to deform the tissue of interest (if possible and safe to do so), which will be a light to moderate pressure and should not be uncomfortable. This will allow us to measure how the tissue properties change during deformation. The exposure of the gravitational MR elastography transducer lasts only as long as the scan itself, as the device is only activated when that particular scan is being acquired, and it lays dormant for the rest of the scan. The anticipated duration of the scans is one and half hours, with the total study visit requiring 2 to 2.5 hours. This will include MR screening, completion of consent forms, participant positioning and MR scanning. Pilot studies for each body region will allow us to determine the total time required for scanning but will be no shorter than 60 minutes and no greater than 120 minutes, with the time required to position the testing apparatus predominately determining the length of the scan. Participants will be recruited and enrolled into studies for each body region, one at a time. For example, the initial study will recruit participants for the study of extremity skeletal muscle and this will be disclosed at the time of recruitment. Recruitment drives for the other tissues will also specify which tissue is to be scanned in the initial advertisement. Electromyographic recordings of neural drive will be measured in the participants recruited for the skeletal muscle MRI study so that regional neural drive across the muscle can be quantified. Data collection will occur in a single visit, following their MRI scan, with participants positioned in the same manner as in the MRI. The lab session will take an additional 30 – 60 minutes for completion. The EMG recordings will occur immediately after the MRI scan, in a NeuRA laboratory upstairs from the NeuRA MRI scanner. The boundaries of the target muscles (e.g. in the calf – medial gastrocnemius, soleus, tibialis anterior; and in the tongue – genioglossus, geniohyoid, superior longitudinal muscle) will be identified with ultrasound. Fine-wire electrodes will be inserted intramuscularly into the muscle belly under ultrasound guidance to known depths and distances such that the EMG data can be mapped back to the 3D model. For the multi-unit recordings, sterile Teflon-coated stainless steel fine-wire electrodes with the ends of the wires bared for 2mm will be inserted along the midline of the muscle. For the single-unit recordings, the ends of the electrodes will be trimmed to reduce recording surface area. Surface electrodes will be positioned superficially to muscle in the upper and lower extremities, and to act as the ground for experiments. Participants will be asked to perform the same voluntary tasks as they performed in the scanner and the neural input while doing so will be measured. This includes both passive recordings (e.g. in the calf at 4 muscle lengths achieved by rotating ankle joint, and tongue during quiet breathing and as the tongue is stretched anteriorly using dental tape) and during voluntary, isometric contractions (e.g. by pushing the foot against an immovable foot plate or protruding the tongue at levels 10 or 20% of the maximal).