|Year : 2022 | Volume
| Issue : 2 | Page : 126-132
18F-FDG positron emission tomography imaging of cortical reorganization in spinal trauma
Jigyasa Chopra, Maria M D'souza, Abhinav Jaimini, Rajnish Sharma, Sanjiv Saw, Santosh Pandey, Yachna Solanki
Department of Nuclear Medicine and PET-CT Imaging, Institute of Nuclear Medicine and Allied Sciences, New Delhi, India
|Date of Submission||24-Aug-2021|
|Date of Decision||19-Oct-2021|
|Date of Acceptance||30-Nov-2021|
|Date of Web Publication||08-Jul-2022|
Dr. Abhinav Jaimini
Department of Nuclear Medicine and PET-CT Imaging, Institute of Nuclear Medicine and Allied Sciences, Brig SK Mazumdar Marg, Timarpur, New Delhi - 110 054, Delhi
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Objective: Spinal cord injury (SCI) extensively impacts the sensorimotor reorganization in the brain. The effects can be both anatomical and functional. To date, not many studies using 18F-Fluoro-2-Deoxyglucose positron emission tomography (18F-FDG PET) to evaluate metabolic changes in the brain are done. Understanding such changes is crucial for developing clinical management and evidence-based rehabilitation strategies for these patients. Subjects and Methods: In this study, we compared 18F-FDG PET imaging of 6 SCI patients with complete paraplegia and 19 controls. Statistical parametric mapping software was utilized to compare the images on a voxel to voxel basis (significance level P < 0.05 and clusters having >50 voxels). Results: The study showed raised metabolism in supplementary motor areas, comprehension centers, some areas in the parietal and temporal lobe, putamen and cerebellum while reduced metabolic uptake in areas like anterior cingulate gyrus, hippocampus and sensory cortical areas when SCI patients were compared against healthy controls. The frontal lobe showed varied results where certain regions showed higher metabolism while the others showed lower in patients compared with controls. Conclusion: Cerebral deafferentation or disuse atrophy can be linked with reduced metabolism while raised uptake can be associated with initiation and planning of movement and cognitive changes in the brain posttrauma.
Keywords: Brain, Fluoro-2-Deoxyglucose, positron emission tomography, spinal cord injury, statistical parametric mapping
|How to cite this article:|
Chopra J, D'souza MM, Jaimini A, Sharma R, Saw S, Pandey S, Solanki Y. 18F-FDG positron emission tomography imaging of cortical reorganization in spinal trauma. Indian J Nucl Med 2022;37:126-32
|How to cite this URL:|
Chopra J, D'souza MM, Jaimini A, Sharma R, Saw S, Pandey S, Solanki Y. 18F-FDG positron emission tomography imaging of cortical reorganization in spinal trauma. Indian J Nucl Med [serial online] 2022 [cited 2022 Sep 27];37:126-32. Available from: https://www.ijnm.in/text.asp?2022/37/2/126/350248
| Introduction|| |
In the mammalian brain, the primary somatosensory and motor cortices are spatially organized such that neural activity relating to specific body parts can be somatopically mapped onto an anatomical “homunculus.” This organization creates an internal body representation that is fundamental for precise motor control, spatial awareness, and social interaction. In this sort of arrangement, there is a competitive battle among different parts of the body to gain space in the cortical field: the more a part of the body is used, the more cortical space it gains to the detriment of adjacent body parts. This continuous reorganization is also a part of normal life and sensorimotor learning., However, the reorganization is extreme in certain scenarios like spinal trauma. Traumatic spinal cord injury (SCI) is a major source of morbidity and mortality throughout the world. A recent study in 2018 showed the overall global incidence of traumatic SCI was 10.5 cases/100,000 persons. What is of concern is that the mean age of patients afflicted with SCI is merely around 33 years. The injury is very disabling with the limited recovery of function expected. The quality of life (QoL) of adults with chronic Traumatic-SCI falls significantly below that of the general population in most domains. It is critical to understand changes after cortical reorganization to help in better rehabilitation with minimal cognitive impairment. Neuroplasticity after SCI involves metabolic and structural changes. Magnetic resonance imaging (MRI) or computerized tomography (CT) are modalities that have been widely used to evaluate anatomical changes in such cases. Glucose metabolism provides both energy and precursors for the biosynthesis of neurotransmitters. Since glucose is required at the synaptic level for neurotransmitters, we can conclude deafferentation will lead to altered glucose uptake in SCI patients. Positron emission tomography (PET) is one such functional modality that uses glucose analog 18F-Fluoro-2-Deoxyglucose (FDG) to generate 3-dimensional (3D) images of the brain. Till date, not much research has been done on the functional changes in various areas of the brain using PET as an imaging modality. Understanding both these key structural and functional sequences in such patients and defining their effects on clinical outcomes is the key to the development of evidence-based rehabilitative therapy. We undertook this study to document the changes in glucose metabolism post-SCI at around 6 months.
| Subjects and Methods|| |
This was a prospective study, from March 2017 to January 2018, eleven patients with paraplegia post-SCI were enrolled for the FDG-PET scan. Patients also had a routine MRI examination to rule out any morphological brain lesion. The patients with any history of head injury in the past were excluded. Due to this exclusion criterion six patients who had paraplegia due to SCI in the past 4–7 months were scanned and included in the study.
A control group of 19 healthy subjects, with no history of any neurological or psychiatric illness, were included for a normal database for comparison.
All patients underwent 18F-FDG-PET/CT examination.
Fluoro-2-Deoxyglucose-positron emission tomography procedure
All subjects were required to come with 4–6 h fasting but with unrestricted water intake on the day of the PET study. Blood glucose level was measured in each case and an upper limit of 150 mg/dl was set as the cut-off for 18F-FDG injection.
Each patient was injected 245–296 MBq (5–8 mCi) of F-18 FDG intravenously followed by a rest period of 60 min with open eyes in a silent, dimly lit room. This was followed by scan acquisition on a Discovery STE16 camera (General Electric Medical Systems, Milwaukee, WI, USA). This scanner has a transaxial resolution full width half maximum (FWHM) of 5.12 mm for 3D mode at 1 cm offset from the center of the field of view.
The patient was imaged supine with the head positioned in a headrest. An initial scout of the head was followed by low dose computerized tomography (CT) (120 kVp, 110 mA) of the head for attenuation correction and anatomical localization. The patient was moved into the PET gantry and a 3D emission scan was obtained for 10 min single-bed position. Images were reconstructed using a 3D VUE algorithm and viewed on a Xeleris workstation general electric (GE). Maximum intensity projection, plain PET, and fused PET/CT images were generated. DICOM images of the Pet study were imported for “Statistical Parametric Mapping” (SPM) analysis.
Statistical parametric mapping analysis
SPM-5 (http://www.fil.ion.ucl.ac.uk/spm) which was implemented on a tool called MATLAB (https://www.mathworks.com/products/matlab.html) platform was used for voxel-based statistical analysis of images. DICOM images of patient and control groups were converted to analyze format using MRIcro medical image viewer software (http://www.psychology.nottingham.ac.uk). The images were spatially normalized and smoothed by an isotropic 10 mm FWHM filter. SPM analysis was done to characterize patient group scans using the general linear model. The patient group was compared statistically to the reference group of 19 healthy control subjects with a two-sample t-test, resulting in the generation of T statistics. The measurements were assumed to be independent and have unequal variance between levels. Proportional scaling to the global mean was used to minimize inter-subject variability. Proportional scaling basically scales each image according to a reference count, which is the global brain activity to a physiologically realistic value of 50 ml/dl/min. Hence, SPM analysis essentially compares regional differences in relative glucose metabolism. In the end, the SPM. mat file containing the specified design matrix was generated. Using this file contrasts were defined thus providing a map of voxels showing increased or decreased glucose metabolism in patient group as compared to the control group above the statistical threshold of P < 0.05 and a threshold of at least 50 voxels in a cluster was applied and t-maps [Figure 1] and [Figure 2] were obtained. After calculating the t statistics, SPM converts the t statistics to Z scores. Z scores are a way that SPM uses to display and analyze the P values from the t statistics [Figure 3] and [Figure 4]. The statistical “t” maps thus obtained were overlaid onto the T1-weighted MRI template image provided by SPM5 and saved as a portable document format for further viewing [Figure 5]. Increased glucose metabolism was represented in the “hot” colors scale and decreased glucose metabolism in “winter” colors scale. Significant clusters were further correlated using the SPM Anatomy toolbox which combines probabilistic cytoarchitectonic maps and functional imaging data.
|Figure 1: Tmap image showing relatively increased 18F-FDG uptake in patients in comparison with controls|
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|Figure 2: Tmap image showing relatively decreased 18F-FDG uptake in patients in comparison with controls|
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|Figure 3: Relatively higher glucose uptake in patients with spinal cord injury compared with controls. x,y and z coordinates in Talairach space; Z =Z score of statistical parametric mapping; P corr= Corrected p value; P uncorr=uncorrected p value; T= T value|
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|Figure 4: Relatively lower glucose uptake in patients with spinal cord injury compared with controls. x,y and z coordinates in talairach space; Z =Z score of statistical parametric mapping; P corr= Corrected p value; P uncorr=uncorrected p value; T= T value|
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|Figure 5: Slice overlay images in transaxial sections using the data represented in Hot and Winter color scales|
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| Results|| |
In this study, FDG PET scans of brains of 6 SCI patients (all males; mean age ± standard deviation, 39.1 ± 9.9 years; range 22–52 years) were compared with that of 19 controls. All the patients were paraplegics with a mean time interval postinjury of around 6 ± 2 months.
Analysis revealed certain cortical areas showing hypermetabolism in SCI patients in comparison to the controls [Figure 4]. These areas included bilateral supplementary motor cortex (leftsupplementary motor area [SMA] [x/y/z = ‒4/‒4/60, Z = 4.85] and right SMA [x/y/z = 10/‒2/66, Z = 4.14]), right superior temporal gyrus/Wernicke's area (x/y/z = 68/‒12/4, Z = 2.32), right inferior temporal gyrus (x/y/z = 40/6/‒44, Z = 5.59), left inferior temporal gyrus (x/y/z = ‒42/4/‒42, Z = 4.65) and left medial temporal lobe (x/y/z = ‒34/20/‒40, Z = 3.86), right angular gyrus (x/y/z = 50/‒56/32, Z = 3.29), right supramarginal gyrus (x/y/z‒52/‒46/26, Z = 3.04) and right superior parietal lobule (x/y/z = 40/‒54/56, Z = 2.52), left inferior frontal gyrus (x/y/z = ‒40/30/4, Z = 2.96), left middle orbital gyrus (x/y/z = ‒38/58/‒10, Z = 2.95), right inferior frontal gyrus (x/y/z = 30/26/‒18, Z = 4.22), and right superior frontal gyrus (x/y/z = 16/68/20, Z = 2.53) bilateral putamen (left putamen [x/y/z = ‒18/6/10, Z = 4.07) and right putamen (x/y/z = 22/4/10, Z = 4.57]) and left cerebellum (x/y/z = ‒42/‒42/‒38, Z = 2.40).
On the contrary, hypometabolism was seen [Figure 5] in the postcentral gyrus (somatosensory cortex, x/y/z = ‒54/‒24/58, Z = 3.31), right hippocampus (x/y/z = 20/‒16/‒16, Z = 4.13), right middle frontal gyrus (x/y/z = 38/52/4, Z = 2.68), left middle frontal gyrus (x/y/z = ‒34/30/36, Z = 2.68), left superior frontal gyrus (x/y/z = ‒18/28/62, Z = 2.72), and left rectal gyrus (x/y/z = ‒8/48/‒16, Z = 2.78). The T value was generated for the left anterior cingulate cortex (ACC) (x/y/z = ‒6/48/6, T = 2.09), but the Z score was not generated.
| Discussion|| |
To improve the QoL of young adults with traumatic-SCI with better rehabilitation with minimal cognitive impairment, it is critical to understand changes from cortical reorganization. Neuroplasticity after SCI involves metabolic and structural changes.
The frontal cortex showed regions of hypermetabolism and hypometabolism. The frontal cortex works in association with other cortical areas and performs diverse functions such as facilitating attention to incoming stimuli from the primary sensory regions. Its close functional relation to other sensorimotor areas could be an explanation of varied glucose metabolism in several areas within this lobe. It also participates with other brain regions in aspects of learning and memory, attention, and motivation. Lack of motivation and depression caused by the disease burden and more dependency on others to perform daily tasks could be an explanation of the same. Many previously conducted studies have also shown decreased grey matter volume in the prefrontal cortical areas which parallels our results. In a study done by Yoon et al. significant structural and functional abnormalities were seen in the prefrontal cortex. Furthermore, Wrigley et al. reported that patients with SCI had significant grey matter atrophy in the medial prefrontal cortex. Chen et al. found bilateral grey matter volume loss in the orbitofrontal cortex (OFC), part of the frontal cortex, could have possibly shown changes because it is an important relay of the limbic system regulating feelings, generating reward activity, emotional states, and cognitive function decision making., OFC in patients with SCI could be associated with depression and with emotional and cognitive impairment after the injury. Chen further suggested that the atrophy increased with the injury duration.
Few studies have shown a decrease in the Gross merchandise value (GMV) primary motor cortex (M1), while on the contrary, some other studies done elsewhere showed no such evidence.,,,, In this study, there were no appreciable differences in the glucose metabolism in the primary motor areas (M1), in SCI patients compared with controls. Collaterals from the adjacent cells can lead to the continued activation of the axotomized cell and could be one possible explanation for no change in metabolic activity in the M1 region.
Our study revealed decreased glucose metabolism in the postcentral gyrus similar to previously published literature., In the somatosensory areas, a direct injury doesn't happen rather it is a result of deafferentation after SC trauma. Animal models in such cases have shown a fraction of brain shrinkage. This thus could be an explanation for altered function. Wallerian degeneration More Details is another possible explanation. Henderson et al. in their study via measuring the GMV showed changes in somatosensory areas and also suggested that reorganization such as the medial shift in the area of little finger representation occupying greater areas previously occupied by lower limbs lowered the further GMV changes.
This study showed increased glucose metabolism in the bilateral SMA, cerebellum, and putamen. GMV in SMA was shown to be decreased in a study done by Jutzeler et al. The mental stimulation of motor tasks and the ideation of walking can activate such areas. Thus, the increased metabolism in the bilateral SMA, cerebellum, and putamen found in our study were likely due to the preparation and execution of motor tasks which the patients were unable to execute due to paraplegia. An old study done in 1997 by Roelecke showed increased glucose metabolism in SMA and putamen which matches with our results.
Hou et al. in their study discovered that GMV was decreased in the primary motor cortex, primary somatosensory cortex, and SMA. The inconsistencies between the results of different studies led Hou et al. to suspect that prolonged exposure to rehabilitation exercise or medication, and methodological differences between studies may contribute to the consistencies across studies.
Our study also showed an increase in glucose metabolism in areas of the parietal lobes and cerebellum. Such outcomes were also seen in the study by Curt et al. however, showed raised uptake when the patient was asked to do hand movements in paraplegics which were compared against healthy controls. The most likely explanation thus is due to higher intention to move limbs in comparison to normal controls. The dependence on upper limbs increases in these paraplegic patients to execute bodily movements.
Additionally, Wernicke's area (superior temporal gyrus) and parts of Broca's area in the left inferior frontal gyrus (pars triangularis) showed increased glucose metabolism. We believe as there is a limited motor activity in paraplegics, the brain in order to retain or increase the cognitive inputs, has to rely on other sensory systems like auditory and visual cortices. This study showed insignificantly decreased metabolism of glucose in the ACC (T = 2.09 and Z score not generated) and hippocampus. Some authors have reported GMV reduction in the dorsal ACC in their MRI studies.,,, Yoon et al. demonstrated both structural and functional abnormality via analyzing using both PET-CT and MRI modalities in the dACC region of the brain. Volume reduction in anatomical studies may be compared to a decrease in metabolism in functional PET studies. The dorsal ACC mainly plays role in conflict monitoring between competing stimuli and provides a continuously updated prediction of expected cognitive demand to optimize future behavioral responses. In SCI patients, sensory inputs have been found to be partially or fully lost. Thus the reduction in the GMV has been related to disuse atrophy in these patients., In our study, the ACC showed lower glucose metabolism, however, no Z score was assigned by SPM, most likely due to shorter time intervals between jury and scanning.
Limitations in this study were that the number of subjects with SCI included in this study is low and the study was not done at different time intervals to establish the chronology of neuroplastic changes.
The changes in glucose metabolism post-SCI suggest remodelling of brain functional areas. Relatively hypermetabolism was noted in brain regions involved in attention and initiation of movement and may be related to secondary disinhibition of these regions. Hypometabolism can be attributed to disuse atrophy and neuroplastic changes in the brain.
We would like to thank Dr. Madhavi Tripathi, Addl. Professor, AIIMS, Delhi for her inputs regarding SPM software and preparing the manuscript.
Financial support and sponsorship
The work was done under DRDO funded project INM-321.
Conflicts of interest
There are no conflicts of interest.
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