Practical Clinical Measurement of Radiotracer Concentration in Blood: Initial Device Concept and Feasibility Testing

Abstract

Kinetic analysis of PET data requires continuous measurement of radioactivity in the arterial blood throughout the acquisition time, termed the arterial input function. The arterial input function is used as an input to compartmental modeling, which can be a better predictor of disease progression than SUV measurements from static PET images. Current common methods of measuring blood concentrations include image-derived, population-based, and manual sampling. These all have challenges due to logistical and technologic issues, as well as patient burden. The aim of this study was to design, develop, and assess a device that is practical and effective for the routine measurement of β-emitting radiotracer concentration in blood without the drawbacks of current methods and for which metabolite analysis is not required. Designs that integrated a scintillating fiber and a silicon photomultiplier with a general-purpose venous access catheter for in vivo measurement were considered. Other design requirements included miniaturization, high sampling rates, and stopping power for β-particles. Preliminary prototypes were designed to test the feasibility of the concept. Phantom tests were developed to mimic human vasculature. Tests of linearity, sensitivity, signal-to-noise ratios, the impact of vein diameter, and the influence of γ-radiation were conducted. Prototype sensors were constructed using 2 different diameters of polystyrene-based scintillating fibers. Fibers were custom-polished and fixed to a silicon photomultiplier. Sensor output was linear, with = 0.999 over the range from 0.037 to 9.25 MBq/mL. Absolute sensitivity was approximately 450 counts per second per MBq/mL. Measured signal-to-noise ratios ranged from 1.2:1 to 3.2:1 using a blood-to-tissue concentration ratio of 1:1. Sensor output increased with vein diameter and showed no sensitivity to γ-radiation. In experiments with phantom models, the prototype provided accurate measurements of β-emitting radiotracer concentration. The design will be refined for in vivo testing. The ability to routinely gather blood input function data would facilitate the adoption of kinetic modeling of PET data.

Simulation study of a coincidence detection system for non-invasive determination of arterial blood time-activity curve measurements

“…In both cases ( 18 F and 15 O), the coincident rates show that the BTAC can be described by the system. Less noise is noted for the BTAC described due to 15 O as the activity used in the simulation was 4 times higher than that of 18 F.…”

“…2b) would also produce count rates acceptable to the determination of the BTAC. We performed simulations of the count rate capabilities for the wristPET2 system using a decaying point source experiment, with a 1-ml point source of activity (14 MBq of 18 F at starting time) located within an 8-cm-diameter water-only phantom, entirely in the FoV of the system in 3 different positions corresponding to where the arteries may be found. The origin of the detection system remained as the same point as for the wristPET 1 system.…”

“…We also investigated differences in sensitivity due to the use of different radiotracers for 18 F and 15 O; given that these radiotracers are commonly used in brain studies where large vessels or blood pools are unlikely to be in the imaging field of view and cannot be used for image-based input functions. The use of these radiotracers for imaging studies nominally uses different levels of injected activity of approximately 250 MBq and 1000 MBq for 18 F and 15 O respectively.…”

“…Simulations were performed with the wristPET2 system using fits to measured BTAC corresponding to injections of approximately 200 and 1000 MBq of 18 F and 15 O respectively in order to evaluate the characteristics of the wristPET2 system to high and low count rates. Simulations were performed to compare the count rates between in the case of 18 F and 15 O simulations, inclusive of the arterial pulsation and BTAC mathematical models (Fig.…”

“…Recent work with phantoms has also investigated the use of prototype system using polystyrene-based scintillating fibers and silicon photomultipliers (SiPM) with a venous access catheter. The system has shown good promise in terms of linearity, sensitivity, and signal-to-noise [18]. Similar work developed a PET-CT system designed to image rheumatoid and psoriatic arthritis in the wrist and the hands of patients, although as yet this system focuses only on highresolution imaging of the joints of the wrist rather than detailing BTAC [19].…”