Kinetic Modeling of Brain [18-F]FDG Positron Emission Tomography Time Activity Curves with Input Function Recovery (IR) Method

Author:

Bucci Marco12345ORCID,Rebelos Eleni2,Oikonen Vesa2ORCID,Rinne Juha1,Nummenmaa Lauri26,Iozzo Patricia7,Nuutila Pirjo28ORCID

Affiliation:

1. Turku PET Centre, Turku University Hospital, 20521 Turku, Finland

2. Turku PET Centre, University of Turku, 20521 Turku, Finland

3. Turku PET Centre, Åbo Akademi University, 20521 Turku, Finland

4. Theme Inflammation and Aging, Karolinska University Hospital, SE-141 86 Stockholm, Sweden

5. Division of Clinical Geriatrics, Department of Neurobiology, Care Sciences and Society, Center for Alzheimer Research, Karolinska University, SE-141 84 Stockholm, Sweden

6. Department of Psychology, University of Turku, 20520 Turku, Finland

7. Institute of Clinical Physiology (IFC), National Research Council (CNR), 56124 Pisa, Italy

8. Department of Endocrinology, Turku University Hospital, 20521 Turku, Finland

Abstract

Accurate positron emission tomography (PET) data quantification relies on high-quality input plasma curves, but venous blood sampling may yield poor-quality data, jeopardizing modeling outcomes. In this study, we aimed to recover sub-optimal input functions by using information from the tail (5th–100th min) of curves obtained through the frequent sampling protocol and an input recovery (IR) model trained with reference curves of optimal shape. Initially, we included 170 plasma input curves from eight published studies with clamp [18F]-fluorodeoxyglucose PET exams. Model validation involved 78 brain PET studies for which compartmental model (CM) analysis was feasible (reference (ref) + training sets). Recovered curves were compared with original curves using area under curve (AUC), max peak standardized uptake value (maxSUV). CM parameters (ref + training sets) and fractional uptake rate (FUR) (all sets) were computed. Original and recovered curves from the ref set had comparable AUC (d = 0.02, not significant (NS)), maxSUV (d = 0.05, NS) and comparable brain CM results (NS). Recovered curves from the training set were different from the original according to maxSUV (d = 3) and biologically plausible according to the max theoretical K1 (53//56). Brain CM results were different in the training set (p < 0.05 for all CM parameters and brain regions) but not in the ref set. FUR showed reductions similarly in the recovered curves of the training and test sets compared to the original curves (p < 0.05 for all regions for both sets). The IR method successfully recovered the plasma inputs of poor quality, rescuing cases otherwise excluded from the kinetic modeling results. The validation approach proved useful and can be applied to different tracers and metabolic conditions.

Funder

Center of Excellence in Cardiovascular and Metabolic Diseases

University of Turku

Turku University Hospital

Åbo Akademi University

Finnish Cultural Fundation

Academy of Finland

Finnish Diabetes Foundation

Sigrid Juselius Foundation

The Gyllenberg Stiftelse

Publisher

MDPI AG

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