positron emission tomography (PET)

Summary

Positron emission tomography (PET) is an in vivo functional neuroimaging technique that provides three-dimensional quantitative images of a wide range of physiological parameters, such as blood flow, glucose metabolic rate, protein synthesis, and receptor density and affinity (Phelpsetal.1979,1986).PET is also a noninvasive technique that is suitable for use in a number of neuroscientific fields of study, both in normal volunteers and in patients. PET is also a noninvasive technique that is applicable to normal volunteers and patients in many areas of neuroscience.

Operation method

Experimental positron emission tomography of the human brain

Principle

PET can essentially be thought of as an in vivo radiation autoradiography technique, in which a biomolecule of interest is first labeled with a short-lived positron-emitting nuclide produced by a cyclotron and then injected into the body intravenously. A positron tomograph surrounding the head of this human body will dynamically record the 511 keV conformal photon pairs produced by the tracer's in vivo positron annihilation. After correcting the acquired data for scattering and tissue attenuation, tomographic calculations are used to reconstruct an absolutely quantized 3D distribution of positron emitters in the brain. Finally, the time-dependent tracer concentration maps were converted to physiological parameter maps using mathematical modeling. Due to the intrinsic poor spatial resolution and low signal-to-noise ratios of PET, it is often necessary to average multiple PET images using either the corresponding MRI structural information or anatomical stencils, as shown in Fig. 39-4 for the complete process of PET manipulation.

Materials and Instruments

Positron Emission Nuclides
Medical compact cyclotron Positron-labeled radioactive compounds Positron Imager

Move

move

PET procedures for human neuroscience research vary largely according to the radiotracer used; however, they share common features with each other and can be represented by the most widely used PET experimental protocol, i.e., imaging of cognitive function using radioactive water.

I. Cognitive Brain Function Imaging with ^H215O Preparation

1. Automated syringe preparation. Insert new sterile lines, valves and saline bags. Start the gas pedal and water production line. Calibrate the radioactive water production system to ensure a volume of 5-6 mCi per injection. save a dose of product in a sterile vial and send it to the laboratory for quality control.

2. PET room preparation. Install the various laboratory equipment required for brain activation (computer monitor, headphones, etc.), and behavioral response recording equipment (electrooculogram, electrocardiogram, mouse pad, etc.). If necessary, hang a black screen around the PET instrument.

3. Subject preparation. Bring a helmet (or head rest) and install the necessary equipment (reflectors, headphones, etc.), the subject supine in the PET examination bed, the head thief fixed to the head rest, in the left upper extremity to establish intravenous access, and connected to the water syringe.

4. Subject position. The subject site is positioned within the PET field of detection and the anatomical landmarks are aligned using the laser positioning line of the PET instrument. A positional reference mark is made on the skin surface of the subject with an ink pen (to control the position of the subject's head throughout the PET experiment).

Acquisition

5. Transmission scanning. Brain transmission scanning with ECATHR+ is standardized to lOmin, with a total of approximately 130M counts acquired.

6. Production of radioactive water. Radioactive water was collected in a water syringe for 6 min while the subject was prepared for the cognitive experiment. The subject's head position is adjusted again by turning on the PET instrument laser positioning line 1 min before the formal injection.

7. Emission scanning (Figure 39-6). Initiate water injection, cognitive stimulation, and PET acquisition. Classically, water is injected first, and cognitive stimulation is initiated 30 s after the water enters the subject's vein. PET acquisition is initiated when the radioactivity reaches the brain, i.e., when the total head count rate is more than 400% above background. After each 90-s acquisition, the head position is confirmed by turning on the laser locator line and the injected dose is entered in the experimental record book. As needed, the water production can be restarted to prepare for the next step in the experiment, and the subject can be questioned.

8. Image reconstruction. The 63-layer cross-sectional image is reconstructed online after a single acquisition for quality checking. The classical reconstruction parameters are: 128x128 matrix, 3D filter parameters, attenuation, scattering and random event correction. The raw data were stored on long-term storage media and the reconstructed images were stored in the experimental folder.

9. Repeat steps 6~8 until the whole program is completed. A typical classical brain activation experiment consists of 8~12 repetitive injections, each separated by 8 min (Figure 39-6).

10. After completing the entire experiment, interview the subject and check the calibration of the water syringe.

Image processing

Figure 39-5 shows the different steps in the exhortation process of PET data, and Table 39-3 shows some of the free software packages available for each step.

11. The complete set of images obtained by visual inspection is excluded from obvious artifacts, and the manufacturer's image mode is transformed into the standard (ANALYZE) mode.

12. Single case study. Align the images from each acquisition to the first acquisition using the AIR software package. PET images were aligned to 3DMRI images when possible. Determine the brain contour on the MRI map and calculate the average activity of the brain for each acquisition and use this as a normalization factor. Calculate the contrast image (task image-contrast image), threshold, and overlay the image on the MRI image to observe the results.

13. Conduct a multi-subject study using SPM.

Results

This section presents the complete PET research protocol (experimental design, acquisition, data analysis, and results) obtained from silent verb generation experiments with 15O-labeled water.

I. Experimental design

Starting with SnodgrassVanderwartPicture260, a series of well-defined nouns were selected. Nouns that are mono- or disyllabic, can be generated within IOs with at least 3 verbs, and have a high initial response-related intensity were chosen to form a lexicon for application in PET studies. Six right-handed young male volunteers (aged 21-25 years) were used as subjects for PET and 15O-labeled water, and each subject underwent 6 normalized local cerebral blood flow (NrCBF) measurements in 2 consecutive experimental conditions, each of which was repeated 3 times: (i) a silent control condition; and (ii) silent generation of semantically related verbs from nouns read out through a headset at a frequency of ○?IHz. Subjects' eyes were closed during the experiment and they were completely protected from light.

Scanning process

For each experiment, 31 consecutive layers of the whole brain were acquired by PET visualization using an ECAT953B/31 model with a layer resolution of 5 mm. The emission scanning acquisitions were performed with the septum extended, i.e., in 2D mode. A 60 mCi15O-labeled water was injected intravenously in a pellet, and the acquisition started 80 s after the radioactivity reached the brain (the image was reconstructed by correcting for the subtraction of the head tissue established by the transmission scanning method). In addition to PET imaging, each subject underwent a 0.5T GEMRMAX magnetic resonance examination to obtain high-resolution Tl-weighted images of the whole brain in the transverse and sagittal directions at a thickness of 3 mm.

Data analysis

As a pre-processing step, image alignment between PET-PET and PET-MRI was performed for each subject by applying AIR software, and then PET data were analyzed by both methods.

Single case analysis

The raw images acquired in 3 repetitions under each experimental condition were not spatially normalized, and an individual determination algorithm was used to process the NrCBF difference images obtained after averaging the 3 repetitions. In each case, the difference image was 31 layers with a layer thickness of 3.375_. After Bonfemmi correction, the value of statistical significance per plane was set to 0.05. The object area detected by this algorithm was precisely localized using a detailed analysis of the brain anatomy of the case. Three-dimensional volume maps of the brain in each case were generated from the MRI cross-sectional maps using a special software (Voxtool), which was further differentiated and showed surface and section images of both hemispheres in three orthogonal directions. The major cerebral fissures in each individual were carefully determined on the MRI images, especially the fissure defining the inferior frontal gyrus. In this study, it was not possible to utilize SPM for individual case analysis. In fact, since there were only 6 2DPET images per subject, the degree of freedom was too low (d/=4) for the required statistical analysis.

Inter-case stereo averaged data

The image results of each case were rearranged and normalized to the Talairach null hypothesis using the image transformation tool in the SPM software package. The normalized images were smoothed by a 16 mm GaussianKernel filter function, and finally statistically processed by SPM with a statistical significance threshold of 0.001 and no correction for multiple comparisons.

Results Single-case analysis

Significant activation was detected in the left inferior frontal gyrus of subjects 2, 5, and 6, with activation on the right side in subject 4 (Fig. 39-7, top row). In the left inferior frontal gyrus activation area (Broca's area) of Nos. 2, 5, and 6, subject 6 was localized in the deltoid region, and Nos. 2 and 5 in the insula; the peculiarity of subject 4 was that the activation was located in the right inferior frontal gyrus in the insula, which extended forward to the deltoid region (i.e., the right Broca's equivalent area). This suggests that the hemisphere of linguistic dominance in our typical right-handed subject is on the right side.

Inter-case stereo mean data

The lower half of Figure 39-7 shows the results obtained from SPM analysis, analyzed with a 0.001 uncorrected statistical threshold. The main activation areas are located in the paramotor area, the left inferior frontal gyrus, and the superior facial gyrus on both sides. Note also the activation of the primary visual cortex.

Comparison of mean functional anatomy between and within cases

The averaged results partially reflect activated brain regions in most subjects, such as the left inferior frontal gyrus (3/6 cases). However, it is possible that the mean activated area performance between cases stemmed from unusually strong activation in 1 or 2 cases, such as superior temporal cortex or visual cortex activation seen only in subject #5. In contrast, sometimes the activation areas seen in a single case fail to show up on the average image between cases. Such single cases of activation may be true positives, i.e., indicate individual differences in functional neuroanatomy, but they may also be false positives. In the present group of 6 standard right-handed subjects, the measurements demonstrated significant functional variability between individuals. Individualized functional patterns reflect a high degree of variability in the size and intensity of activated brain areas. The present experiment is an excellent example of the need for individualized analysis of PET brain activation experiments and its complementarity to the classical between-example averaging analysis1 . The current combination of sensitive individualized measurement algorithms and precise anatomical analysis of the brain facilitates the study of accurate and quantitative relationships between structure and function in the human brain.

For more product details, please visit Aladdin Scientific website.

https://www.aladdinsci.com/