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Image-derived input function for human brain using high resolution PET imaging with [C](R)-rolipram and [C]PBR28.

Zanotti-Fregonara P, Liow JS, Fujita M, Dusch E, Zoghbi SS, Luong E, Boellaard R, Pike VW, Comtat C, Innis RB - PLoS ONE (2011)

Bottom Line: Using the image input methods that gave the most accurate results with Logan analysis, we also performed kinetic modelling with a two-tissue compartment model.All methods gave higher scores with [(11)C](R)-rolipram, which has a lower metabolite fraction.Compartment modeling gave less reliable results, especially for the estimation of individual rate constants.

View Article: PubMed Central - PubMed

Affiliation: Molecular Imaging Branch, National Institute of Mental Health (NIMH), National Institutes of Health (NIH), Bethesda, Maryland, United States of America.

ABSTRACT

Background: The aim of this study was to test seven previously published image-input methods in state-of-the-art high resolution PET brain images. Images were obtained with a High Resolution Research Tomograph plus a resolution-recovery reconstruction algorithm using two different radioligands with different radiometabolite fractions. Three of the methods required arterial blood samples to scale the image-input, and four were blood-free methods.

Methods: All seven methods were tested on twelve scans with [(11)C](R)-rolipram, which has a low radiometabolite fraction, and on nineteen scans with [(11)C]PBR28 (high radiometabolite fraction). Logan V(T) values for both blood and image inputs were calculated using the metabolite-corrected input functions. The agreement of image-derived Logan V(T) values with the reference blood-derived Logan V(T) values was quantified using a scoring system. Using the image input methods that gave the most accurate results with Logan analysis, we also performed kinetic modelling with a two-tissue compartment model.

Results: For both radioligands the highest scores were obtained with two blood-based methods, while the blood-free methods generally performed poorly. All methods gave higher scores with [(11)C](R)-rolipram, which has a lower metabolite fraction. Compartment modeling gave less reliable results, especially for the estimation of individual rate constants.

Conclusion: OUR STUDY SHOWS THAT: 1) Image input methods that are validated for a specific tracer and a specific machine may not perform equally well in a different setting; 2) despite the use of high resolution PET images, blood samples are still necessary to obtain a reliable image input function; 3) the accuracy of image input may also vary between radioligands depending on the magnitude of the radiometabolite fraction: the higher the metabolite fraction of a given tracer (e.g., [(11)C]PBR28), the more difficult it is to obtain a reliable image-derived input function; and 4) in association with image inputs, graphical analyses should be preferred over compartmental modelling.

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The average concentrations of radioactivity in whole blood (solid line) and parent radioligand in plasma (dashed line) over time for [11C](R)-rolipram (n = 12) (A) and [11C]PBR28 (n = 19) (B).The main figures show the first 20 minutes of the curves and the inserts the remaining part. Although the shape of the whole blood curves was similar for the two tracers, the relative concentration of parent and metabolites differed. The mean ratio of concentration of parent radioligand in plasma to total radioactivity in whole blood (C) showed that [11C](R)-rolipram remained the predominant component of whole blood radioactivity throughout the scan. In contrast, radiometabolites of [11C]PBR28 became the predominant component of whole blood radioactivity after the first few minutes.
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pone-0017056-g002: The average concentrations of radioactivity in whole blood (solid line) and parent radioligand in plasma (dashed line) over time for [11C](R)-rolipram (n = 12) (A) and [11C]PBR28 (n = 19) (B).The main figures show the first 20 minutes of the curves and the inserts the remaining part. Although the shape of the whole blood curves was similar for the two tracers, the relative concentration of parent and metabolites differed. The mean ratio of concentration of parent radioligand in plasma to total radioactivity in whole blood (C) showed that [11C](R)-rolipram remained the predominant component of whole blood radioactivity throughout the scan. In contrast, radiometabolites of [11C]PBR28 became the predominant component of whole blood radioactivity after the first few minutes.

Mentions: The shape of the whole-blood curves was very similar for the two tracers (Figure 2AB), with a concentration peak at ∼90 seconds and a rapid decline thereafter; however, the relative concentration of parent and metabolites differed (Figure 2C). [11C](R)-rolipram remained the predominant portion of blood radioactivity throughout the scan. The mean parent/whole blood ratio was of about 1 (0.99±0.24) at 60 minutes after injection, and 0.80±0.30 at 90 minutes. In contrast, for [11C]PBR28, radiometabolites became the predominant component of blood radioactivity for most of the scan. The mean parent/whole blood ratio was of about 1 (0.96±0.13) at 4 minutes after injection, and 0.07±0.02 at 90 minutes. The mean/whole blood ratios are calculated from all the subjects used in this study (n = 12 for [11C](R)-rolipram and n = 19 for [11C]PBR28).


Image-derived input function for human brain using high resolution PET imaging with [C](R)-rolipram and [C]PBR28.

Zanotti-Fregonara P, Liow JS, Fujita M, Dusch E, Zoghbi SS, Luong E, Boellaard R, Pike VW, Comtat C, Innis RB - PLoS ONE (2011)

The average concentrations of radioactivity in whole blood (solid line) and parent radioligand in plasma (dashed line) over time for [11C](R)-rolipram (n = 12) (A) and [11C]PBR28 (n = 19) (B).The main figures show the first 20 minutes of the curves and the inserts the remaining part. Although the shape of the whole blood curves was similar for the two tracers, the relative concentration of parent and metabolites differed. The mean ratio of concentration of parent radioligand in plasma to total radioactivity in whole blood (C) showed that [11C](R)-rolipram remained the predominant component of whole blood radioactivity throughout the scan. In contrast, radiometabolites of [11C]PBR28 became the predominant component of whole blood radioactivity after the first few minutes.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3045425&req=5

pone-0017056-g002: The average concentrations of radioactivity in whole blood (solid line) and parent radioligand in plasma (dashed line) over time for [11C](R)-rolipram (n = 12) (A) and [11C]PBR28 (n = 19) (B).The main figures show the first 20 minutes of the curves and the inserts the remaining part. Although the shape of the whole blood curves was similar for the two tracers, the relative concentration of parent and metabolites differed. The mean ratio of concentration of parent radioligand in plasma to total radioactivity in whole blood (C) showed that [11C](R)-rolipram remained the predominant component of whole blood radioactivity throughout the scan. In contrast, radiometabolites of [11C]PBR28 became the predominant component of whole blood radioactivity after the first few minutes.
Mentions: The shape of the whole-blood curves was very similar for the two tracers (Figure 2AB), with a concentration peak at ∼90 seconds and a rapid decline thereafter; however, the relative concentration of parent and metabolites differed (Figure 2C). [11C](R)-rolipram remained the predominant portion of blood radioactivity throughout the scan. The mean parent/whole blood ratio was of about 1 (0.99±0.24) at 60 minutes after injection, and 0.80±0.30 at 90 minutes. In contrast, for [11C]PBR28, radiometabolites became the predominant component of blood radioactivity for most of the scan. The mean parent/whole blood ratio was of about 1 (0.96±0.13) at 4 minutes after injection, and 0.07±0.02 at 90 minutes. The mean/whole blood ratios are calculated from all the subjects used in this study (n = 12 for [11C](R)-rolipram and n = 19 for [11C]PBR28).

Bottom Line: Using the image input methods that gave the most accurate results with Logan analysis, we also performed kinetic modelling with a two-tissue compartment model.All methods gave higher scores with [(11)C](R)-rolipram, which has a lower metabolite fraction.Compartment modeling gave less reliable results, especially for the estimation of individual rate constants.

View Article: PubMed Central - PubMed

Affiliation: Molecular Imaging Branch, National Institute of Mental Health (NIMH), National Institutes of Health (NIH), Bethesda, Maryland, United States of America.

ABSTRACT

Background: The aim of this study was to test seven previously published image-input methods in state-of-the-art high resolution PET brain images. Images were obtained with a High Resolution Research Tomograph plus a resolution-recovery reconstruction algorithm using two different radioligands with different radiometabolite fractions. Three of the methods required arterial blood samples to scale the image-input, and four were blood-free methods.

Methods: All seven methods were tested on twelve scans with [(11)C](R)-rolipram, which has a low radiometabolite fraction, and on nineteen scans with [(11)C]PBR28 (high radiometabolite fraction). Logan V(T) values for both blood and image inputs were calculated using the metabolite-corrected input functions. The agreement of image-derived Logan V(T) values with the reference blood-derived Logan V(T) values was quantified using a scoring system. Using the image input methods that gave the most accurate results with Logan analysis, we also performed kinetic modelling with a two-tissue compartment model.

Results: For both radioligands the highest scores were obtained with two blood-based methods, while the blood-free methods generally performed poorly. All methods gave higher scores with [(11)C](R)-rolipram, which has a lower metabolite fraction. Compartment modeling gave less reliable results, especially for the estimation of individual rate constants.

Conclusion: OUR STUDY SHOWS THAT: 1) Image input methods that are validated for a specific tracer and a specific machine may not perform equally well in a different setting; 2) despite the use of high resolution PET images, blood samples are still necessary to obtain a reliable image input function; 3) the accuracy of image input may also vary between radioligands depending on the magnitude of the radiometabolite fraction: the higher the metabolite fraction of a given tracer (e.g., [(11)C]PBR28), the more difficult it is to obtain a reliable image-derived input function; and 4) in association with image inputs, graphical analyses should be preferred over compartmental modelling.

Show MeSH