Creating Dynamic Images of Short-lived Dopamine Fluctuations with lp-ntPET: Dopamine Movies of Cigarette Smoking

Abstract

We describe experimental and statistical steps for creating dopamine movies of the brain from dynamic PET data. The movies represent minute-to-minute fluctuations of dopamine induced by smoking a cigarette. The smoker is imaged during a natural smoking experience while other possible confounding effects (such as head motion, expectation, novelty, or aversion to smoking repeatedly) are minimized. We present the details of our unique analysis. Conventional methods for PET analysis estimate time-invariant kinetic model parameters which cannot capture short-term fluctuations in neurotransmitter release. Our analysis - yielding a dopamine movie - is based on our work with kinetic models and other decomposition techniques that allow for time-varying parameters 1-7. This aspect of the analysis – temporal-variation- is key to our work. Because our model is also linear in parameters, it is practical, computationally, to apply at the voxel level. The analysis technique is comprised of 5 main steps: pre-processing, modeling, statistical comparison, masking and visualization. Preprocessing is applied to the PET data with a unique ‘HYPR’ spatial filter 8 that reduces spatial noise but preserves critical temporal information. Modeling identifies the time-varying function that best describes the dopamine effect on 11C-raclopride uptake. The statistical step compares the fit of our (lp-ntPET) model 7 to a conventional model 9. Masking restricts treatment to those voxels best described by the new model. Visualization maps the dopamine function at each voxel to a color scale and produces a dopamine movie. Interim results and sample dopamine movies of cigarette smoking are presented.

Evaluation of (‐)‐[18F]Flubatine‐specific binding: Implications for reference region approaches

“…PET data were acquired in list mode with a high-resolution research tomograph (HRRT; Siemens/CTI) started 90 min after the beginning of radiotracer administration, the time when tissue radiotracer levels reach equilibrium (Hillmer et al, 2016), and continued for an additional 120 min. Subjects smoked a cigarette of their preferred brand starting at 125 min after radiotracer injection, taking 1 puff every 30 s for 5 min while in the scanner, following a previously described paradigm (Morris et al, 2013). Arterial blood samples were acquired to measure the parent input function as previously described (Hillmer et al, 2016).…”

News and views on in-vivo imaging of neurotransmission using PET and MRI

“…Towards this goal, models that include a dynamic association rate as part of the kinetic model have been developed 72,75 . To date, these models have been successfully applied for the detection of dopamine release or exogenous D2 receptor binding using the radiotracer [ 11 C]raclopride for evaluating cigarette smoking 62,120 or drug injections 50 . The applicability and validation for the use of such methods for other radiotracers remains to be investigated in more detail.…”

A review of positron emission tomography studies exploring the dopaminergic system in substance use with a focus on tobacco as a co-variate

“…), and analysis techniques [3]. To address some of these limitations, a novel PET image analysis approach incorporating a time-varying component to capture transient changes in DA throughout the scan, was recently developed [17]. This technique showed sex-differences in the dopaminergic response, whereby smoking a cigarette rapidly and consistently elicited right ventral striatal DA release in male smokers and dorsal striatal DA release in female smokers [18].…”