Characterising Frailty Using Magnetic Resonance Imaging

The study will recruit females aged over 65 years (n=51), from those attending hospital clinics for older people at both campuses of Nottingham University Hospitals National Health Service (NHS) Trust. A member of the clinical care team working within the clinic will identify potential participants who are 'frail', 'mildly frail/vulnerable' and 'non-frail' using the Clinical Frailty Scale (measured as part of routine care), and the electronic Frailty Index. Clinic staff will make the initial approach to patients about the study and if the individual is interested in taking part, clinic staff will inform the research team. A researcher will then approach the interested individual and provide a study information sheet outlining study procedures. Potential participants will then be given a week to consider participating in the research.

If individuals wish to participate, they will be invited to the David Greenfield Human Physiology laboratories at the Queen's Medical Centre. Here, researchers will explain the study again to volunteers and answer any questions that they may have. Volunteers will be asked to sign an informed consent document prior to any other study procedures being undertaken. Participants will initially have their height and body mass recorded and will complete questionnaires assessing their suitability to have magnetic resonance imaging (MRI) scans, their cognitive ability and independence across activities of daily living.

Each participant's frailty status will be confirmed via the Fried Frailty phenotype assessment which will include a timed 15ft (4.57m) walk, hand grip strength, and questionnaires (Center for Epidemiologic Studies Depression Scale, Minnesota Leisure Time Activity Questionnaire). Participants who do not exhibit any frailty components will be classed as non-frail, those showing one or two frailty components will be classified as pre-frail, and those presenting three or more components will be classed as frail. These measures of frailty severity will take approximately 30 minutes to complete.

Knee extensor strength and power measurements will then be made. They will involve participants being seated in a chair and supported within the measuring apparatus (a padded chair with back support at 90°) using straps (similar to a seat belt) which go across their hips and shoulders. The participant's ankle will be positioned against a lever arm of the equipment and again held in place by a padded support. The isometric strength assessment will involve the participant pushing against the lever arm with maximum effort whilst it is fixed and unable to move. A total of 3 contractions lasting ~2 seconds will be performed with a 1 min rest between each. Muscle power and fatigue will be assessed on the same machine but this time the lever arm will move at a fixed rate. Participants will be asked to extend their leg (as if kicking a ball) 10 times with the lever arm speed at a slow speed (60 degrees per second) and 10 at a faster speed (180 degrees per second). These tests of muscle power output have been administered routinely to elderly volunteers in the literature and our laboratory. However, if these tests are not tolerable for participants, we will terminate the test. Knee extensor measurements will take approximately 30 minutes to complete.

Measurements of thigh muscle motor unit recruitment and motor control (a measure of the electrical activity within the muscle) will then be taken. Measurements will involve placing adhesive non-invasive ECG pads on to the participant's thigh, and a small (24-gauge) needle inserted into the thigh muscle to a depth of ~0.5-2.5cm (depending on amount of subcutaneous fat present). Participants will then be asked to gently contract their thigh muscle (the limb will not be in motion) and the electrical activity of the muscle will be measured. In total, this measure will take approximately 40 minutes to complete. Once completed, the electrodes will be removed and the needle insertion site covered with a small adhesive dressing. Muscle activity measures will take approximately 40 minutes to complete.

On a separate day, following the visit to the physiology laboratories, participants will be invited to the Sir Peter Mansfield Imaging Centre at the University of Nottingham. Here, they will undergo MRI scanning to gather images of the heart, brain, skeletal muscle and fat content within the body. Participants will be made comfortable on the scan table using pillows and pads to support their back, neck and joints. They will be asked to lie as still as possible during the scan protocol and occasionally perform some short breath holds (necessary to acquire certain scans). In total, the time spent in the scanner will be approximately 60 minutes. However, lying still within the MRI scanner for ~60 minutes may be burdensome for elderly participants. Therefore, we will offer short comfort breaks after 15 minutes and 40 minutes of scanning, during which participants may leave the scan room to use the bathroom and consume refreshments if needed. This will not affect the scan procedure or image collection.