Tomoki Fujii1, Krishna R. Singh2, Bill Bordeau3, Joao A. Lima1, and Bharath Ambale-Venkatesh1
1Johns Hopkins University, Baltimore, MD, United States, 2Prairie Vascular Institute, Springfield, IL, United States, 3Zimmer Biomet Biologics, Warsaw, IN, United States
Synopsis
Peripheral artery disease is a major public health concern particularly among the elderly. Although measures such as ankle-brachial index and segmental pressures have been used to characterize disease severity, MRI techniques allow us to assess subclinical vascular function and morphology and may help improve our understanding of vascular adaptations. In a small pilot study, we test whether hyperemia-induced BOLD oxygenation changes are a viable measure of tissue oxygenation in the foot and if they represent the reduced oxygenation seen in PAD.PURPOSE
To perform blood-oxygen level dependent (BOLD) MRI of the foot to identify perfusion defects caused by arterial occlusion in patients with peripheral arterial disease (PAD).
METHODS
Our hypothesis is that hyperemia-induced BOLD-perfusion measurement could sensitively identify the theorized perfusion defects seen in PAD patients in the foot as a result of arterial occlusion as seen in magnetic resonance angiography (MRA) of the foot. To test this hypothesis, we performed BOLD MRI and MRA of the foot in a 1.5-T Siemens Avanto scanner with a 16-channel foot coil. BOLD MRI of the foot was performed from above-ankle to bottom of the symptomatic foot (for patients) or a randomly chosen foot (for volunteers) using a T2*-weighted gradient echo EPI sequence with TR/TE = 2250/24, 20 slices with slice thickness = 5mm, image matrix = 64x64, pixel spacing = 3.75x3.75 mm, with 400 dynamic measurements over 15 mins (temporal resolution = 2.25 s). A pressure cuff was placed below the level of the knee (and above the calf muscle) and was inflated to a pressure to cause complete occlusion of the pedal artery (no pedal pulse using Doppler). Measurements were performed throughout 90 secs of pre-cuff inflation, 300 secs of cuff inflation, and ~500 secs post-cuff deflation. Anillustration curve is shown in Figure 1a with a BOLD image in Figure 1b. Using the signal intensities, we measured the overshoot = (Smax-So)/So; reserve = (Smin-So)/Smin; dynamic range = (Smax-Smin)/So; and time-to-peak in the flexor halluces and digitorum brevis muscles as seen in T1-weighted anatomic images of the foot. MRA was performed with a TWIST sequence with TR/TE = 3.22/1.18, flip angle = 25 degs, image matrix 384x202, pixel spacing = 0.92x0.92 mm was performed with 0.3 ml/kg of Dotarem (Guerbet, France). Stenosis was quantified in the anterior tibial (ATA), dorsalis pedis (DPA), posterior tibial (PTA) and plantar arteries (PA) based on the following grading system: 0% (0), 1-49% (I), 50-90% (II), 90-99% (III), and 100% (IV). All analysis was performed on Osirix (ROI Enhancement plugin was used). The 3 volunteers (39 yr old male, 50 yr old female and 60 yr old male) were asymptomatic on the Rutherford scale while the 3 patients (84, 79 and 71 yrs; all male) were classified as Rutherford stage 3/4.
RESULTS
Figure 2a and 2b show the MRA and the BOLD image of a volunteer while 2c and 2d show that of a patient. The volunteer has patent arteries while the patient 100% occlusion of the XX and XX arteries. The time to peak after cuff deflation was 45, 128 and 108 seconds for the volunteers while it was 104, 221 and 313 seconds for the 3 patients. The overshoot was 2.7%, 1.3% and 3.6% for the volunteers while it was 2.6%, 4.4% and 3.28% for the patients. The reserve was significantly higher for the volunteers (11%, 17.7% and 23%) as compared to the patients (7.5%, 0.4% and 2%). The dynamic range was similarly different between the volunteers (12.2%, 16.2%, and 21.5%) and patients (9.3%, 4.6% and 5.1%). The MRA revealed that while one volunteer had grade I occlusion (1-49%) of the MPA while the remaining volunteers had no occlusion. Figure 3 (Table) has more information regarding patients.
DISCUSSION
The wide prevalence of PAD and its adverse consequences
define it as a public health imperative, and the ineffectiveness of
claudication pharmacology in a large percent of PAD sufferers marks this
condition as an unmet medical need. PAD is characterized by intermittent
claudication or the presence of significant stenosis or occlusion of
infrainguinal arteries. Several therapies have been proposed as a viable
treatment option by way of angiogenic mechanisms. While it is hypothesized that
there is improved tissue oxygenation and increased muscle perfusion of the
ischemic muscles, the exact underlying mechanisms are still unknown. We try to
use MRI to address this area of need. While contrast-enhanced dynamic MRA has
long been used for visualizing peripheral vasculature, the use of BOLD MRI for
assessment of tissue oxygenation in the foot has not been widely tested before
in PAD, even if it has been tested in the calf muscles in a few studies
1234. In this small pilot study of
3 volunteers and 3 patients, we show using hyperemic BOLD MRI that volunteers
had a greater oxygen reserve and a greater dynamic working range as compared to
patients with occlusion of their pedal arteries.
CONCLUSION
Hyperemic BOLD MRI may be a sensitive marker of oxygenation in the foot and maybe an alternate and viable option for assessment of therapy efficacy in PAD patients.
Acknowledgements
We would like to thank Zimmer Biomet Biologics for their support of this study.References
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