Foot ulcer healing is of particular clinical importance because foot complications, such as ulceration, are the leading causes of hospitalization in patients with diabetes Mellitus (DM).¹ One key prognostic factor that is currently lacking in diabetic foot care is an accurate indicator of the local micro-vascular bed basal flow (skeletal muscle perfusion) and responsiveness (skeletal muscle oxygenation) to help guide diagnosis and intervention. The purpose of this project is to develop and evaluate an MRI based foot oximetry for assessing the microcirculation in foot skeletal muscle, at rest and during exercise.

Theory

The method was used to calculate tissue oxygen extraction fraction (OEF) with the magnetic susceptibility effect on deoxyhemoglobins.^2,3. Briefly speaking, a multi-slice 2D triple-echo asymmetric spin-echo sequence was implemented to acquire source images. With varying time offset τ from TE/2 , a special transverse relaxation rate R2’ (= R2 – R2*) with a decay time of 2τ can then be calculated as:

$$$R'_{2}= \frac{4}{3}\lambda \times \triangle \chi_{0} \times Hct \times OEF \times Y_{a} \times B_{0}$$$ (1)

Where λ is the blood volume fraction containing deoxyhemoglobin, representing tissue venous blood volume; Hct is the fractional hematocrit; B₀ is the main magnetic field strength; $$$\triangle \chi_{0}$$$ is 0.27 ppm. Both $$$R'_{2}$$$ and λ can be calculated by asymmetric spin echo signals as a function of τ.⁴

MRI oximetry study protocol

Five healthy volunteers (72 ± 3 years, 4M) and 5 subjects with DM (Type I or II, 65 ± 4 years, HbA1c = 7.2 ± 1.8%, 4M) without documented history of peripheral artery disease were scanned for the measurement of foot OEF. All imaging sessions were performed on a 3.0 T Trio Siemens whole-body MR system. The subjects lay supine on the MRI table with their right feet inside a head coil (receiver only). Subjects were instructed at rest or to contract their intrinsic foot muscles to flex their toes at the metatarsal phalangeal joints.³

After the scout imaging, three-slice oximetric imaging was performed at rest and started at 30 sec after the start of toe flexion (Figure 1 a). The imaging parameters for oximetry measurements were: TR = 4 s; FOV = 340 x 255 mm²; matrix size = 64 x 48 and interpolated to 128 x 96; slice thickness = 8 mm; total acquisition = 3 min 48 s.

Image processing and data analysis

An OEF map of each slice was first created using custom-made software. ⁵ A maximal intensity projection map was then obtained from the three OEF maps. This projection image was further processed for angiosomes. i.e., the entire foot area (excluding the calcaneal region) was classified into angiosomes based on four different OEF ranges: 0 ≤ OEF ≤ 0.3; 0.3 < OEF ≤ 0.5; 0.5 < OEF ≤ 0.7; 0.7 < OEF ≤ 1.0 (Figure 1 b). Each region’s area is calculated as a percent of the total area.

Table 1 lists areas in percentages for foot OEF in 4 different ranges at rest and during the toe exercise, as well as the percent differences of these areas between two states. For the first three ranges in which foot OEF was less than 0.7, there was no significant difference observed in these parameters between healthy subjects and subjects with DM. However, this percent difference of foot OEF within the 0.7 – 1.0 range was significantly larger in healthy subjects than in subjects with DM (8 ± 4 % in healthy vs. -4 ± 4% in DM). Box plots are presented in Figure 2. Figure 3 shows the foot oximetry angiosomes in a healthy subject and a subject with DM.

For the first time, absolute tissue oxygen extraction fraction was measured in the foot at rest and during a toe flexion exercise. The most significant finding is that changes in foot OEF from rest to toe exercise were significantly different between healthy and DM in the area of 0.71-1.0 range in the foot oximetry angiosomes.

Due to the heterogeneity of diabetic foot ulcers, as many as 54% of foot ulcers cannot be simply categorized to a specific angiosome due to dual blood supplies. ⁶ Our foot oximetry allows for direct determination of the low- or high- oxygenated regions that may be supplied by one or more pedal arteries. This approach may be more appropriate for patients with DM because impaired local microcirculation is common in DM.