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Feasibility of Longitudinal Brain PET with Real-Time Arterial Input Function in Rats

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Abstract

Purpose

Preclinical dynamic brain PET studies remain hampered by the limitations related to the measurement of the arterial input function (AIF). In this regard, the use of an arterial-venous shunt is a promising method for the generation of real-time AIFs, but its application in longitudinal studies is still impeded by the cumbersome surgeries and high failure rates. We studied the feasibility and reproducibility of double arterial-venous shunt strategies for conducting longitudinal PET studies with real-time AIFs in rats.

Procedures

We studied the feasibility of double arterial-venous shunts in rats in the right/left inguinal region and evaluated inter-animal and intra-animal AIF reproducibilities. Image-derived input function (IDIF) was also obtained for comparison. Dynamic brain FDG PET studies were conducted to estimate kinetic constants and Cerebral Metabolic Rate of Glucose (CMRglc) obtained from standard 2-tissue compartment (2TCM) and Patlak analysis.

Results

We showed that longitudinal AIFs from double arterial-venous shunts can be obtained with very high success rate of the surgeries (88 %). Our results provided highly reproducible AIF measurements with low inter-animal variabilities (11 %) and intra-animal variabilities (5–10 %) that were included into the kinetic models, such that longitudinal rate constants and CMRglc can be efficiently estimated without bias associated to the double shunt. Our results indicated that longitudinal IDIF can be also generated without bias along time but showing higher intra-animal uncertainties.

Conclusions

We have demonstrated the feasibility and high reproducibility of conducting longitudinal AIF measurements and consequently accurate kinetic modeling using arterial shunt method.

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Acknowledgments

This work was partially supported by the projects ED431F 2017/04 (Xunta de Galicia), EAPA_791/2018 (Interreg UE) and RYC-2015/17430 (Ramón y Cajal, Pablo Aguiar).

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Authors and Affiliations

  1. Molecular Imaging Group, Department of Radiology, Faculty of Medicine, University of Santiago de Compostela (USC), IDIS, Campus Vida, 15782, Santiago de Compostela, Spain

    David Rey-Bretal, Noemí Gómez-Lado, Álvaro Ruibal & Pablo Aguiar

  2. Nuclear Medicine Department and Molecular Imaging Group, IDIS and University Hospital Santiago de Compostela (CHUS), Travesía da Choupana s/n, 15706, Santiago de Compostela, Spain

    Alexis Moscoso, Jesús Silva-Rodríguez, Álvaro Ruibal & Pablo Aguiar

  3. Pharmacy Department and Pharmacology Group, IDIS and University Hospital CHUS, Travesía da Choupana s/n, 15706, Santiago de Compostela, Spain

    Anxo Fernández-Ferreiro

Authors
  1. David Rey-Bretal
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  2. Alexis Moscoso
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  3. Noemí Gómez-Lado
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  4. Anxo Fernández-Ferreiro
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  5. Jesús Silva-Rodríguez
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  6. Álvaro Ruibal
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  7. Pablo Aguiar
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Contributions

DRB made the surgeries and wrote the manuscript; AM prepared the figures and contributed to the analysis of data; NGL verified the analytical methods and worked out almost all of the technical details; AFF and JSR helped analyze the results; AR helped design and instruct the experiment; PA conceived the study and revised the manuscript. All authors discussed the results and commented on the manuscript.

Corresponding author

Correspondence to Pablo Aguiar.

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The authors declare that they have no conflict of interest.

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Rey-Bretal, D., Moscoso, A., Gómez-Lado, N. et al. Feasibility of Longitudinal Brain PET with Real-Time Arterial Input Function in Rats. Mol Imaging Biol 23, 350–360 (2021). https://doi.org/10.1007/s11307-020-01556-y

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  • DOI: https://doi.org/10.1007/s11307-020-01556-y

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