Studying Metabolic Brain Connectivity Using 2-Deoxy-2-[18F]Fluoro-D-Glucose Dynamic Positron Emission Tomography at the Single-subject Level

Summary

The acquisition of dynamic positron emission tomography (PET) data and reconstruction into time frames allows for metabolic brain connectivity analysis at the single-subject level. We describe a method to acquire [¹⁸F]FDG dynamic PET data of the rat brain and obtain a connectivity matrix through the extraction of time-activity curves of volumes of interest.

Abstract

To this day, metabolic brain connectivity is mostly studied on a group level through the acquisition of static positron emission tomography (PET) data of multiple subjects. Our research groups are currently studying changes in metabolic connectivity across multiple time points following an intracerebral hemorrhage on an intrasubject level in rats. To investigate intrasubject metabolic brain connectivity, temporal information of the tracer uptake in different brain regions is required, which can be achieved through dynamic PET. In this publication, we give a detailed description of our data acquisition and analysis protocol.

Dynamic PET data of the rat brain are acquired on a dedicated preclinical PET system using 2-deoxy-2-[¹⁸F]fluoro-D-glucose ([¹⁸F]FDG) as tracer. The tracer is injected intravenously as a bolus at the start of the PET scan. During the 60 min acquisition, animals are sedated with medetomidine.

After acquisition, the PET data are reconstructed into thirty 2 min time frames using an iterative reconstruction algorithm (Maximum-Likelihood Expectation-Maximization). A parcellated atlas consisting of multiple volumes of interest (VOIs) is used to extract time-activity curves of each VOI, which are then used to calculate the Pearson correlation coefficient between each pair of VOIs.

This dynamic PET protocol enables the assessment of metabolic connectivity differences between two single scans, rather than between groups of scans. This approach allows for the study of changes in metabolic connectivity within a single subject across different time points, or for the comparison of an individual's metabolic connectivity to a normal database. Such comparisons could be useful for tracking disease progression or aiding in the diagnosis of neurological disorders characterized by disrupted communication between brain regions, such as epilepsy or dementia.

Introduction

Positron emission tomography (PET) is a molecular imaging technique commonly used in research as well as in clinical settings. Due to the development of various PET tracers, PET can be used to study disease pathophysiology and monitor disease progression and response to treatments¹. One of the most widely used radiotracers is 2-deoxy-2-[¹⁸F]fluoro-D-glucose ([¹⁸F]FDG), which allows for the imaging of glucose metabolism, indicative of cellular activation. It is utilized in oncology for diagnosis, staging, and prognosis; in neurology, commonly in the context of neurodegenerative diseases such as dementia; and in cardiology, ....

Protocol

All procedures are in accordance with the European guidelines (directive 2010/63/EU), and the protocol was approved by the local Animal Ethical Committee of Ghent University (ECD 23/33). Twelve Sprague Dawley rats (six female, six male) were included in the study. Their PET scans were obtained using the following protocol at multiple time points ranging from 2 weeks before to 18 weeks after an induced intracerebral hemorrhage. At the time of the first scan, all animals were 18 weeks of age and the females weighed 244.8 &.......

Discussion

The protocol provided here guides users through the process of acquiring 1 h dynamic PET data using [¹⁸F]FDG as a tracer in rats. In the end, a correlation matrix of VOIs is obtained, which can be used to assess metabolic connectivity on a single-subject level. Experienced researchers may adjust the protocol to fit their specific needs at various points, for example, by using a different radiotracer, acquisition time, or time frame widths for image reconstructions, and selecting relevant VOIs in the data analy.......

Materials

Name	Company	Catalog Number	Comments
Antisedan	Orion Pharma		Atipamezole hydrochloride 5 mg/mL
BD Micro-Fine+ insulin syringe 1 mL	BD	324827	0.33 mm (29G) x 12.7 mm
BD Microlance 3 Needles 30 G x 1/2"	BD	304000	30 G x 1/2"; 0,3 x 13 mm
BD Plastipak syringe 1 mL	BD	303172	for infusion pump
BTPE-10 Polyethylene tubing	Instech		0.11x.024in (.28x60mm)
Domitor	Orion Pharma	1070499	Medetomidine hydrochloride 1 mg/mL
Fusion 100 infusion pump	Chemyx Inc.	07100	Newer model available: Fusion 100X
Isoflutek 1000 mg/g	Alivira		Isoflurane
MOLECUBES β-CUBE with CUBEFLOW software	MOLECUBES NV		Preclinical PET scanner
PMOD Software version 4.4	Bruker Corporation		http://www.pmod.com; quantification of PET data
Saline	B. Braun	394496	NaCl 0.9%
Vidisic eye gel	Vidisic		Carbomerum 980 2 mg/g