Since it was first proposed as a diagnostic tool for angina almost 75 years ago [
1], treadmill exercise stress testing quickly became, and still remains, an essential tool in the detection and treatment of heart disease. The Bruce Treadmill Test, first published in 1963 [
2], is the most commonly used exercise test protocol in the US [
3,
4], and has been shown to have high diagnostic and prognostic value [
5,
6]. The addition of imaging to the exercise stress test further improves sensitivity and specificity, providing greater diagnostic accuracy than exercise ECG alone [
7,
8]. According to some estimates, over 10 million stress studies are performed in the US each year in conjunction with nuclear or echocardiographic imaging [
9]. While CMR stress imaging has demonstrated recent success and is potentially superior to stress echocardiography [
10] and SPECT imaging [
11], pharmacological stress has remained the only practical approach to CMR stress imaging due to the lack of MRI-compatible exercise and monitoring equipment. Exercise is preferred to pharmacologic stress testing because it links physical activity to symptoms and ischemia [
12]. The exercise test itself offers additional important information such as exercise capacity, blood pressure response, development of arrhythmias, and the presence of symptoms such as chest pain during exercise [
13]. Certain exercise parameters alone such as inability to complete 6 minutes of the Bruce treadmill protocol [
14] and inability to reach 85% of age-predicted maximum heart-rate indicate significant risk of coronary events [
15]. Pharmacologic stress is only indicated in those patients unable to undergo exercise stress testing for reasons such as de-conditioning, peripheral vascular disease, and orthopedic disabilities [
16,
17]. Stress CMR using a MRI-compatible bicycle ergometer has been previously demonstrated [
18‐
22]), but fatigue of the quadriceps muscles in patients is a limitation to achieving target heart rate and maximal cardiovascular stress [
23]. Untrained subjects will typically only achieve 80% – 90% of their treadmill maximum oxygen consumption on a bicycle ergometer [
24].
While treadmill exercise is the physiologically preferred method of cardiovascular stress testing, it presents significant challenges for use with MRI. Treadmills are typically powered by electromagnetic motors and contain a multitude of ferromagnetic parts, precluding their use in close proximity to an MRI magnet. Bringing the treadmill, monitoring equipment, and staff into the MRI room would allow it to function much like a standard exercise stress lab. Furthermore, positioning the treadmill as close to the MRI patient table as possible would minimize the time from exercise to imaging. Any time delay is critical, since function imaging must be completed within 60 seconds post-exercise [
12,
25] to capture the exercise-induced wall motion abnormalities which may begin to disappear almost immediately after exercise [
26‐
28]. Additionally, traveling any distance immediately following maximal exercise could be unsafe for severely ill or de-conditioned cardiac patients.
Besides the difficulties of safely operating exercise and monitoring equipment in the magnetic field of the MRI room, image acquisition during conditions of maximal cardiovascular stress is exceptionally challenging. Temporal resolution requirements are higher for exercise stress imaging due to elevated heart rates and rapid, heavy breathing. Total scan time must be minimized to acquire all data before exercise-induced ischemia is resolved. Breath-holding may be impossible for patients immediately following maximal exercise stress. Recent advances in MRI hardware and software, such as the TSENSE [
29] method of dynamic parallel imaging, have resulted in significant improvements in the temporal and spatial resolution of real-time and single-shot imaging methods, significantly shortening scan time and eliminating the need for patient breath-hold.
The objectives of this study were to modify a treadmill for use inside the MRI room, to develop real-time imaging protocols for CMR of cardiac function and myocardial perfusion following maximal exercise, and to demonstrate the feasibility of in-room treadmill stress CMR in healthy volunteers. To our knowledge, real-time wall motion and perfusion imaging immediately after maximal treadmill exercise inside the MRI room has not been previously demonstrated.