Toward whole-brain dopamine movies: a critical review of PET imaging of dopamine transmission in the striatum and cortex

Heather Liu¹, Yasmin Zakiniaeiz², Kelly P Cosgrove^{2

3

4

5}, Evan D Morris^{6

7

8

9}

Affiliations

¹ Department of Biomedical Engineering, Yale University, New Haven, CT, USA.
² Interdepartmental Neuroscience Program, Yale University School of Medicine, New Haven, CT, USA.
³ Department of Psychiatry, Yale University, New Haven, CT, USA.
⁴ Department of Neuroscience, Yale University School of Medicine, New Haven, CT, USA.
⁵ Department of Radiology and Biomedical Imaging, Yale University, Yale PET Center, P.O. Box 208048, New Haven, CT, 06510, USA.
⁶ Department of Biomedical Engineering, Yale University, New Haven, CT, USA. evan.morris@yale.edu.
⁷ Interdepartmental Neuroscience Program, Yale University School of Medicine, New Haven, CT, USA. evan.morris@yale.edu.
⁸ Department of Psychiatry, Yale University, New Haven, CT, USA. evan.morris@yale.edu.
⁹ Department of Radiology and Biomedical Imaging, Yale University, Yale PET Center, P.O. Box 208048, New Haven, CT, 06510, USA. evan.morris@yale.edu.

PMID: 29071465
PMCID: PMC5918462
DOI: 10.1007/s11682-017-9779-7

Review

Toward whole-brain dopamine movies: a critical review of PET imaging of dopamine transmission in the striatum and cortex

Heather Liu et al. Brain Imaging Behav. 2019 Apr.

. 2019 Apr;13(2):314-322.

doi: 10.1007/s11682-017-9779-7.

Authors

Heather Liu¹, Yasmin Zakiniaeiz², Kelly P Cosgrove^{2

3

4

5}, Evan D Morris^{6

7

8

9}

Affiliations

¹ Department of Biomedical Engineering, Yale University, New Haven, CT, USA.
² Interdepartmental Neuroscience Program, Yale University School of Medicine, New Haven, CT, USA.
³ Department of Psychiatry, Yale University, New Haven, CT, USA.
⁴ Department of Neuroscience, Yale University School of Medicine, New Haven, CT, USA.
⁵ Department of Radiology and Biomedical Imaging, Yale University, Yale PET Center, P.O. Box 208048, New Haven, CT, 06510, USA.
⁶ Department of Biomedical Engineering, Yale University, New Haven, CT, USA. evan.morris@yale.edu.
⁷ Interdepartmental Neuroscience Program, Yale University School of Medicine, New Haven, CT, USA. evan.morris@yale.edu.
⁸ Department of Psychiatry, Yale University, New Haven, CT, USA. evan.morris@yale.edu.
⁹ Department of Radiology and Biomedical Imaging, Yale University, Yale PET Center, P.O. Box 208048, New Haven, CT, 06510, USA. evan.morris@yale.edu.

PMID: 29071465
PMCID: PMC5918462
DOI: 10.1007/s11682-017-9779-7

Abstract

The mesocorticolimbic dopamine (DA) circuit, comprising the mesolimbic and mesocortical DA pathways, plays a crucial role in reward, cognitive control, and motivation. The positron emission tomography (PET) radiotracer, [C-11]raclopride, has been used widely to image DA receptors and DA changes in the mesolimbic pathway before and after pharmacological and behavioral challenges. In certain circumstances, properties of traditional kinetic models-used to analyze dynamic PET data-are not well-suited to describing the effects of stimulus-induced DA release. To combat model shortcomings, the authors have advanced a suite of models that characterizes PET data in the presence of time-varying DA release. We review select [C-11]raclopride studies of the striatum during cigarette smoking to illustrate the advantages of such models. DA receptors occur in lower density in the cortex than the striatum. This, as well as higher relative background signal, poses a serious challenge to quantitative PET of DA changes in the mesocortical system. Novel high affinity radioligands [F-18]fallypride and [C-11]FLB457 have been used to image mesocortical DA transmission. Models with time-varying terms may also hold the key to optimizing sensitivity to changes in mesocortical DA. As an illustration, we compare recent PET studies of the effect of stress on cortical DA release. Finally, we consider some challenges and strategies for further optimization of sensitivity of PET to stimulus-induced DA changes throughout the whole brain.

Keywords: Dopamine release; Kinetic modeling; Model limitations; Neuroimaging; Smoking; Stress.

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Conflict of interest statement

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval and informed consent

This is a review article and therefore does not contain any new data from studies with human participants or animals performed by any of the authors. To the best of the author’s knowledge, the data reviewed in this article were all acquired in accordance with the ethical standards of the relevant institutional and/or national research committee and with the 1975 Helsinki declaration and its later amendments or comparable ethical standards.

Figures

**Fig. 1**
Simulated PET TACs including the effect of transient DA release. Hollow bars: data window for baseline fit, solid bars: data windows for fits including DA transient. (a) effect of data window on fitted curves with SRTM (solid: fitted curves, dotted: simulated original TAC). Note solid curve that fits the data perfectly *prior* to the effect of the transient at 40 min. (b) effect of data window on estimated change in BP_ND with SRTM, based on 100 simulated noisy TACs. Modified from Sullivan et al. (2013), *Am J Nuc Med Mol Imaging*

**Fig. 2**
A partial set of gamma-variate shaped DA response functions as described by lp-ntPET. Modified from Kim et al. (2014), *Human Brain Mapping*

**Fig. 3**
“Probability of Activation” maps for male (M) and female (F) smokers. Note difference between sexes in right ventral striatum (rVS). A permutation test performed using all 16 subjects showed mean difference in number of activated voxels in rVS between M and F was highly significant (p < 0.01). Right brain is on right. Modified from Cosgrove et al. (2014), *J Neurosci*

**Fig. 4**
DA release during MIST. (A) t-score map based on γ as estimated with LSSRM from Lataster et al., (B) t-score map based on BP_ND as estimated with SRTM from Nagano-Saito et al. Used with publisher’s permission from Lataster et al. (2011), *Neuroimage* and Nagano-Saito et al. (2013), *Synapse*

See this image and copyright information in PMC

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