Quantification of Hand Blood Flow by ⁸²Rubidium Positron Emission Tomography

To the Editor:

Patients with secondary Raynaud phenomenon (RP) are at risk for developing digital ischemia and ulcerations, and amputations.¹ Current treatment options for digital ulcers are limited, hampered by the lack of sensitive methods to quantify hand blood flow. Although Doppler ultrasound is widely accessible for assessing large-vessel blood flow, it lacks standardization for evaluating microvascular tissue perfusion.^2-4 Laser speckle contrast analysis can quantify microvascular blood flow and predict vascular complications in RP; however, it evaluates only superficial blood flow and can be influenced by the skin’s optical properties.⁵ Thermography, an infrared imaging technique, uses heatmaps to assess skin temperature changes indirectly measuring blood flow, but interpreting regional variations can be challenging since heatmaps do not provide quantitative data.⁶

82-rubidium (⁸²Rb) positron emission tomography (PET) myocardial perfusion imaging (MPI) is a robust imaging technique routinely used in cardiology to quantify myocardial blood flow. This method involves administration of ⁸²Rb, a radioactive tracer that behaves similarly to potassium, enabling rapid uptake by muscle cells proportional to blood flow. During PET acquisition, multiple images are captured over time, tracking the movement of ⁸²Rb through the bloodstream. This facilitates the measurement of key variables, such as K1, representing the rate constant for the transfer of ⁸²Rb from blood into tissue, reflecting perfusion. Quantifying myocardial blood flow with ⁸²Rb PET helps detect coronary microvascular disease and provides valuable diagnostic and prognostic information in patients with RP or autoimmune conditions.^7,8 We sought to develop a new method for quantifying hand blood flow by adapting the ⁸²Rb PET MPI technique for hand imaging.

In this case series, we evaluated blood flow quantification of the hand in 7 healthy participants without autoimmune rheumatic conditions or RP (female sex: n = 5, age: 28 [SD 10] years, BMI: 25.3 [SD 2.5; calculated as weight in kilograms divided by height in meters squared]). Participants avoided food and caffeine for 4 hours before the study. Intravenous access was established on the nondominant upper extremity for radioisotope injection. ⁸²Rb PET was performed on a hybrid PET/computed tomography (CT) system equipped with a 64-slice CT scanner (GE Discovery 690; GE Healthcare). The dominant hand was positioned above the left side of the chest (position 1, Figure 1A) approximately 20-30 mm above chest level to avoid scatter from the body. Following a scout image, a low-energy CT (120 kVp, 13 mA) was acquired for attenuation correction. A series of images were captured over time to assess blood flow at rest after intravenous injection of 20 ± 2 mCi of ⁸²Rb. Twenty-seven frames were acquired in list mode with the following time sequences: 14 × 5-s frames; 6 × 10-s frames; 3 × 20-s frames; 3 × 30-s frames; and 1 × 90-s frame. Reproducibility was evaluated by obtaining another set of images (with separate attenuation CT) after repositioning the dominant hand to the right side of the chest (position 2, Figure 1A). PET images were also acquired in 3 participants undergoing reactive hyperemia testing, performed by inflating a blood pressure cuff on the upper arm to 50 mmHg higher than the participant’s systolic blood pressure for 5 minutes. The cuff was released after 5 minutes and ⁸²Rb was delivered 1 minute later, corresponding to peak hyperemia.

• Download figure
• Open in new tab
• Download powerpoint

Figure 1.

Quantification of hand blood flow by 82-rubidium positron emission tomography. (A) The dominant hand was positioned first on the left (position 1) and then on the right side of the chest (position 2). (B) Hands were segmented while avoiding bony structures. (C) Radiotracer time-activity curves in hand (blue) vs background (orange). (D) Correlation between resting K1 values obtained at position 1 and position 2. (E) Comparison of K1 values at rest and after reactive hyperemia.

Reconstructed images were analyzed using Carimas (Turku).⁹ Hands were segmented by using superimposed attenuation CT images, manually contouring the soft tissue of hands while avoiding bony structures (Figure 1B). Background contours were drawn randomly in areas free of body structures approximately the same distance from the chest surface (20-30 mm). Rest and peak hyperemic K1 values were estimated by fitting the ⁸²Rb time-activity curves to a single-compartment tracer kinetic model using the left ventricle as arterial input function. The correlation between resting K1 values was evaluated by Pearson correlation. Hyperemic and resting K1 values were compared by paired t test.

⁸²Rb injection imaging revealed hand radiotracer uptake, which was substantially higher than background activity (Figure 1C). The 1-compartment model described ⁸²Rb kinetics very well (median r² = 0.94). Repeat imaging yielded similar K1 values at the 2 hand positions (rest position 1: 0.015 ± 0.008 mL/min/mL, rest position 2: 0.016 ± 0.009 mL/min/mL, P = 0.17), with excellent correlation between resting K1 values obtained at position 1 and position 2 (r² = 0.90, P = 0.001; Figure 1D). Reactive hyperemia resulted in a significant increase in K1 in the tested 3 healthy participants (hyperemia: 0.028 ± 0.004 mL/min/mL vs rest: 0.012 ± 0.005 mL/min/mL, P = 0.02; Figure 1E).

In conclusion, quantification of hand blood flow with ⁸²Rb PET is feasible and can effectively detect changes in response to reactive hyperemia in healthy participants, although the technique requires expertise in nuclear medicine, can be expensive, and involves insertion of an intravenous line and exposure to radiation. Further studies are required to evaluate whether hand blood flow quantification by ⁸²Rb PET can serve as a novel imaging marker to guide prevention and monitor effectiveness of therapy for digital ulcers in patients with secondary RP.

• Copyright © 2025 by the Journal of Rheumatology