Arterial input function sampling without surgery in rats for positron emission tomography molecular imaging

Croteau, Étienne; Poulin, Éric C.; Tremblay, Sébastien; Dumulon-Perreault, Véronique; Sarrhini, Otman; Lepage, Martin

doi:10.1097/mnm.0000000000000097

“…Blood withdrawal is, however, necessary when chemical analysis of plasma samples is required to quantify metabolites of new radiotracers. Less invasive cannulation points such as the tail artery can then be adopted in conjunction with a microfluidic blood-counting system (33).…”

Section: Discussion Microfluidic Blood-counting Systemmentioning

confidence: 99%

“…Even if manual sampling is considered as the gold standard for AIF measurements, its temporal resolution is limited and may induce distortion in the AIF too (33). Another common reference for nondispersed AIF is the IDIF extracted from a ROI in PET images.…”

Section: Discussion Microfluidic Blood-counting Systemmentioning

confidence: 99%

Real-Time Microfluidic Blood-Counting System for PET and SPECT Preclinical Pharmacokinetic Studies

Convert

¹

,

Lebel

²

,

Gascon

³

et al. 2016

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Small-animal nuclear imaging modalities have become essential tools in the development process of new drugs, diagnostic procedures, and therapies. Quantification of metabolic or physiologic parameters is based on pharmacokinetic modeling of radiotracer biodistribution, which requires the blood input function in addition to tissue images. Such measurements are challenging in small animals because of their small blood volume. In this work, we propose a microfluidic counting system to monitor rodent blood radioactivity in real time, with high efficiency and small detection volume (∼1 μL). Methods: A microfluidic channel is built directly above unpackaged p-i-n photodiodes to detect β-particles with maximum efficiency. The device is embedded in a compact system comprising dedicated electronics, shielding, and pumping unit controlled by custom firmware to enable measurements next to small-animal scanners. Data corrections required to use the input function in pharmacokinetic models were established using calibrated solutions of the most common PET and SPECT radiotracers. Sensitivity, dead time, propagation delay, dispersion, background sensitivity, and the effect of sample temperature were characterized. The system was tested for pharmacokinetic studies in mice by quantifying myocardial perfusion and oxygen consumption with 11 C-acetate (PET) and by measuring the arterial input function using 99m TcO 4 − (SPECT). Results: Sensitivity for PET isotopes reached 20%-47%, a 2-to 10-fold improvement relative to conventional catheter-based geometries. Furthermore, the system detected 99m Tc-based SPECT tracers with an efficiency of 4%, an outcome not possible through a catheter. Correction for dead time was found to be unnecessary for small-animal experiments, whereas propagation delay and dispersion within the microfluidic channel were accurately corrected. Background activity and sample temperature were shown to have no influence on measurements. Finally, the system was successfully used in animal studies. Conclusion: A fully operational microfluidic blood-counting system for preclinical pharmacokinetic studies was developed. Microfluidics enabled reliable and high-efficiency measurement of the blood concentration of most common PET and SPECT radiotracers with high temporal resolution in small blood volume. Radi onuclide-based molecular imaging using PET and SPECT is a leading diagnostic tool in oncology, cardiology, and neurology (1). In research applications, small-animal models are needed to facilitate the development of new drugs, radiotracers, and therapies that can eventually be translated to humans (2). Quantification of metabolic or physiologic disorders using radiotracer pharmacokinetic models requires dynamic blood analysis in addition to tissue imaging data (3). Whole-blood radioactivity as a function of time, the so-called arterial input function (AIF), can be extracted from PET images (4,5), using an intravascular b-microprobe (6,7) or an external blood counter connected to an artery via a catheter (8-10). Fo...

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“…Automated blood sampling methods have been developed to determine the input function [ 8 , 9 ] with a potential for smaller blood volumes. However, the input function from these methods needs to be corrected for propagation delay and dispersion [ 10 ]. A hybrid image and blood sampling method was developed to derive input function for quantification of microPET mouse data [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

Enhanced Extraction of Blood and Tissue Time-Activity Curves in Cardiac Mouse FDG PET Imaging by Means of Constrained Nonnegative Matrix Factorization

Sarrhini

¹

,

D’Orléans-Juste

²

,

Rousseau

³

2023

International Journal of Biomedical Imaging

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We propose an enhanced method to accurately retrieve time-activity curves (TACs) of blood and tissue from dynamic 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) positron emission tomography (PET) cardiac images of mice. The method is noninvasive and consists of using a constrained nonnegative matrix factorization algorithm (CNMF) applied to the matrix ( A ) containing the intensity values of the voxels of the left ventricle (LV) PET image. CNMF factorizes A into nonnegative matrices H and W , respectively, representing the physiological factors (blood and tissue) and their associated weights, by minimizing an extended cost function. We verified our method on 32 C57BL/6 mice, 14 of them with acute myocardial infarction (AMI). With CNMF, we could break down the mouse LV into myocardial and blood pool images. Their corresponding TACs were used in kinetic modeling to readily determine the [18F]FDG influx constant ( K i ) required to compute the myocardial metabolic rate of glucose. The calculated K i values using CNMF for the heart of control mice were in good agreement with those published in the literature. Significant differences in K i values for the heart of control and AMI mice were found using CNMF. The values of the elements of W agreed well with the LV structural changes induced by ligation of the left coronary artery. CNMF was compared with the recently published method based on robust unmixing of dynamic sequences using regions of interest (RUDUR). A clear improvement of signal separation was observed with CNMF compared to the RUDUR method.

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“…This can be achieved using arterial blood sampling [10] which is very invasive and sensitive to errors. A number of methods has been proposed to lower invasiveness of measurement [5] or derive the IF directly from the dynamic PET images. In some cases, blood structure can be directly observed on the images.…”

Section: Introductionmentioning

confidence: 99%

Estimation of input function from dynamic PET brain data using Bayesian blind source separation

Tichý

¹

,

Šmı́dl

²

2015

COMSIS J

0

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Selection of regions of interest in an image sequence is a typical prerequisite step for estimation of time-activity curves in dynamic positron emission tomography (PET). This procedure is done manually by a human operator and therefore suffers from subjective errors. Another such problem is to estimate the input function. It can be measured from arterial blood or it can be searched for a vascular structure on the images which is hard to be done, unreliable, and often impossible. In this study, we focus on blind source separation methods with no needs of manual interaction. Recently, we developed sparse blind source separation and deconvolution (S-BSS-vecDC) method for separation of original sources from dynamic medical data based on probability modeling and Variational Bayes approximation methodology. In this paper, we extend this method and we apply the methods on dynamic brain PET data and application and comparison of derived algorithms with those of similar assumptions are given. The S-BSS-vecDC algorithm is publicly available for download.

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Arterial input function sampling without surgery in rats for positron emission tomography molecular imaging

Abstract: Both minimally invasive manual withdrawal and dispersion-corrected μBC-based blood sampling in the tail artery are reliable methods for deriving AIFs for pharmacokinetic follow-up studies in the same animal.

Cited by 4 publications

References 34 publications

Real-Time Microfluidic Blood-Counting System for PET and SPECT Preclinical Pharmacokinetic Studies

Real-Time Microfluidic Blood-Counting System for PET and SPECT Preclinical Pharmacokinetic Studies

Enhanced Extraction of Blood and Tissue Time-Activity Curves in Cardiac Mouse FDG PET Imaging by Means of Constrained Nonnegative Matrix Factorization

Estimation of input function from dynamic PET brain data using Bayesian blind source separation

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