Arterial input function of an optical tracer for dynamic contrast enhanced imaging can be determined from pulse oximetry oxygen saturation measurements

.. Validation experiments were conducted in rabbits using a small animal oximetry device
(MouseOx, STARR Life Sciences, Oakmont, PA), but the approach is translatable to the clinic,
capitalizing on the ubiquity of pulse oximeters.
In many cases, kinetic modeling requires that the arterial input function (AIF)—the time-dependent arterial concentration of a tracer—be characterized. A straightforward method to measure the AIF of red and near-infrared optical dyes (e.g., indocyanine green) using a pulse oximeter is presented. The method is motivated by the ubiquity of pulse oximeters used in both preclinical and clinical applications, as well as the gap in currently available technologies to measure AIFs in small animals. The method is based on quantifying the interference that is observed in the derived arterial oxygen saturation (SaO2) following a bolus injection of a light-absorbing dye. In other words, the change in SaO2 can be converted into dye concentration knowing the chromophore-specific extinction coefficients, the true arterial oxygen saturation, and total hemoglobin concentration. A simple error analysis was performed to highlight potential limitations of the approach, and a validation of the method was conducted in rabbits by comparing the pulse oximetry method with the AIF acquired using a pulse dye densitometer. Considering that determining the AIF is required for performing quantitative tracer kinetics, this method provides a flexible tool for measuring the arterial dye concentration that could be used in a variety of applications.

General scientific summary In dynamic contrast enhanced optical imaging, a targeted or untargeted optical dye is injected into the subject to recover functional information from a tissue region, such as blood flow, leakage, or molecular binding. The models used to recover the functional information often require that the arterial concentration of dye—also called the arterial input function (AIF)—be characterized. A specialized piece of equipment, known as a pulse dye densitometer (PDD) can be used to measure the AIF in adult humans; however, PDDs are expensive, uncommon and do not function properly in small animals or infants. We present a straightforward method of measuring the AIF using a standard pulse oximeter, which is ubiquitous in both clinical and preclinical settings. When an optical dye is injected, it causes interference in the oxygen saturation measurement. The AIF can be quantified from this interference. As proof-of-principle, we present numerical and experimental results.

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