Image-Derived Input Function for Human Brain Using High Resolution PET Imaging with [11C](R)-rolipram and [11C]PBR28

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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 [ ¹¹C]( R)-rolipram, which has a low radiometabolite fraction, and on nineteen scans with [ ¹¹C]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 [ ¹¹C]( 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., [ ¹¹C]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.

Related collections

Most cited references 34

Record: found
Abstract: found
Article: not found

A molecular and cellular theory of depression.

R S Duman, G Heninger, E J Nestler (1997)

Recent studies have begun to characterize the actions of stress and antidepressant treatments beyond the neurotransmitter and receptor level. This work has demonstrated that long-term antidepressant treatments result in the sustained activation of the cyclic adenosine 3',5'-monophosphate system in specific brain regions, including the increased function and expression of the transcription factor cyclic adenosine monophosphate response element-binding protein. The activated cyclic adenosine 3',5'-monophosphate system leads to the regulation of specific target genes, including the increased expression of brain-derived neurotrophic factor in certain populations of neurons in the hippocampus and cerebral cortex. The importance of these changes is highlighted by the discovery that stress can decrease the expression of brain-derived neurotrophic factor and lead to atrophy of these same populations of stress-vulnerable hippocampal neurons. The possibility that the decreased size and impaired function of these neurons may be involved in depression is supported by recent clinical imaging studies, which demonstrate a decreased volume of certain brain structures. These findings constitute the framework for an updated molecular and cellular hypothesis of depression, which posits that stress-induced vulnerability and the therapeutic action of antidepressant treatments occur via intracellular mechanisms that decrease or increase, respectively, neurotrophic factors necessary for the survival and function of particular neurons. This hypothesis also explains how stress and other types of neuronal insult can lead to depression in vulnerable individuals and it outlines novel targets for the rational design of fundamentally new therapeutic agents.

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Record: found
Abstract: found
Article: not found

Correction for partial volume effects in PET: principle and validation.

Natalie C. Evans, O Rousset, Y. Ma (1998)

The accuracy of PET for measuring regional radiotracer concentrations in the human brain is limited by the finite resolution capability of the scanner and the resulting partial volume effects (PVEs). We designed a new algorithm to correct for PVEs by characterizing the geometric interaction between the PET system and the brain activity distribution. The partial volume correction (PVC) algorithm uses high-resolution volumetric MR images correlated with the PET volume. We used a PET simulator to calculate recovery and cross-contamination factors of identified tissue components in the brain model. These geometry-dependent transfer coefficients form a matrix representing the fraction of true activity from each distinct brain region observed in any given set of regions of interest. This matrix can be inverted to correct for PVEs, independent of the tracer concentrations in each tissue component. A sphere phantom was used to validate the simulated point-spread function of the PET scanner. Accuracy and precision of the PVC method were assessed using a human basal ganglia phantom. A constant contrast experiment was performed to explore the recovery capability and statistic error propagation of PVC in various noise conditions. In addition, a dual-isotope experiment was used to evaluate the ability of the PVC algorithm to recover activity concentrations in small structures surrounded by background activity with a different radioactive half-life. This models the time-variable contrast between regions that is often seen in neuroreceptor studies. Data from the three-dimensional brain phantom demonstrated a full recovery capability of PVC with less than 10% root mean-square error in terms of absolute values, which decreased to less than 2% when results from four PET slices were averaged. Inaccuracy in the estimation of 18F tracer half-life in the presence of 11C background activity was in the range of 25%-50% before PVC and 0%-6% after PVC, for resolution varying from 6 to 14 mm FWHM. In terms of noise propagation, the degradation of the coefficient of variation after PVC was found to be easily predictable and typically on the order of 25%. The PVC algorithm allows the correction for PVEs simultaneously in all identified brain regions, independent of tracer levels.

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Record: found
Abstract: found
Article: not found

Computerized three-dimensional segmented human anatomy.

Z Rattner, I George Zubal, Edward Hoffer … (1994)

Manual segmentation of 129 x-ray CT transverse slices of a living male human has been done and a computerized 3-dimensional volume array modeling all major internal structures of the body has been created. Each voxel of the volume contains a index number designating it as belonging to a given organ or internal structure. The original x-ray CT images were reconstructed in a 512 x 512 matrix with a resolution of 1 mm in the x,y plane. The z-axis resolution is 1 cm from neck to midthigh and 0.5 cm from neck to crown of the head. This volume array represents a high resolution model of the human anatomy and can serve as a voxel-based anthropomorphic phantom suitable for many computer-based modeling and simulation calculations.

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Author and article information

Contributors

: Role: Editor

Journal

Journal ID (nlm-ta): PLoS One

Journal ID (publisher-id): plos

Journal ID (pmc): plosone

Title: PLoS ONE

Publisher: Public Library of Science (San Francisco, USA )

ISSN (Electronic): 1932-6203

Publication date Collection: 2011

Publication date (Electronic): 25 February 2011

Volume: 6

Issue: 2

Electronic Location Identifier: e17056

Affiliations

[1 ]Molecular Imaging Branch, National Institute of Mental Health (NIMH), National Institutes of Health (NIH), Bethesda, Maryland, United States of America

[2 ]CEA/SHFJ, Orsay, France

[3 ]Department of Nuclear Medicine, VU University Medical Center, Amsterdam, The Netherlands

University of Texas, M.D. Anderson Cancer Center, United States of America

Author notes

* E-mail: innisr@ 123456mail.nih.gov

Conceived and designed the experiments: PZ-F J-SL CC RBI. Performed the experiments: PZ-F J-SL ED CC. Analyzed the data: PZ-F J-SL MF SSZ EL RB VWP RBI. Wrote the paper: PZ-F J-SL MF ED SSZ EL RB VWP CC RBI.

Article

Publisher ID: PONE-D-10-04037

DOI: 10.1371/journal.pone.0017056

PMC ID: 3045425

PubMed ID: 21364880

SO-VID: cd06505a-86ac-4492-8bbb-3c1b39f69bf7

Copyright © This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose.

History

Date received : 22 October 2010

Date accepted : 13 January 2011

Page count

Pages: 11

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