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¹⁸F-FDG PET Combined With MR Spectroscopy Elucidates the Progressive Metabolic Cerebral Alterations After Blast-Induced Mild Traumatic Brain Injury in Rats.

ABSTRACT: A majority of blast-induced mild traumatic brain injury (mTBI) patients experience persistent neurological dysfunction with no findings on conventional structural MR imaging. It is urgent to develop advanced imaging modalities to detect and understand the pathophysiology of blast-induced mTBI. Fluorine-18 fluorodeoxyglucose positron emission tomography (¹⁸F-FDG PET) could detect neuronal function and activity of the injured brain, while MR spectroscopy provides complementary information and assesses metabolic irregularities following injury. This study aims to investigate the effectiveness of combining ¹⁸F-FDG PET with MR spectroscopy to evaluate acute and subacute metabolic cerebral alterations caused by blast-induced mTBI. Thirty-two adult male Sprague-Dawley rats were exposed to a single blast (mTBI group) and 32 rats were not exposed to the blast (sham group), followed by ¹⁸F-FDG PET, MRI, and histological evaluation at baseline, 1-3 h, 1 day, and 7 days post-injury in three separate cohorts. ¹⁸F-FDG uptake showed a transient increase in the amygdala and somatosensory cortex, followed by a gradual return to baseline from day 1 to 7 days post-injury and a continuous rise in the motor cortex. In contrast, decreased ¹⁸F-FDG uptake was seen in the midbrain structures (inferior and superior colliculus). Analysis of MR spectroscopy showed that inflammation marker myo-inositol (Ins), oxidative stress marker glutamine + glutamate (Glx), and hypoxia marker lactate (Lac) levels markedly elevated over time in the somatosensory cortex, while the major osmolyte taurine (Tau) level immediately increased at 1-3 h and 1 day, and then returned to sham level on 7 days post-injury, which could be due to the disruption of the blood-brain barrier. Increased ¹⁸F-FDG uptake and elevated Ins and Glx levels over time were confirmed by histology analysis which showed increased microglial activation and gliosis in the frontal cortex. These results suggest that ¹⁸F-FDG PET and MR spectroscopy can be used together to reflect more comprehensive neuropathological alterations in vivo, which could improve our understanding of the complex alterations in the brain after blast-induced mTBI.

SUBMITTER: Li Y

PROVIDER: S-EPMC8012735 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundThe standard MR Dixon-based attenuation correction (AC) method in positron emission tomography/magnetic resonance (PET/MR) imaging segments only the air, lung, fat and soft-tissues (4-class), thus neglecting the highly attenuating bone tissues and affecting quantification in bones and adjacent vessels. We sought to address this limitation by utilizing the distinctively high bone uptake rate constant Ki expected from 18F-Sodium Fluoride (18F-NaF) to segment bones from PET data and support 5-class hybrid PET/MR-driven AC for 18F-NaF and 18F-Fluorodeoxyglucose (18F-FDG) PET/MR cardiovascular imaging.MethodsWe introduce 5-class Ki/MR-AC for (i) 18F-NaF studies where the bones are segmented from Patlak Ki images and added as the 5th tissue class to the MR Dixon 4-class AC map. Furthermore, we propose two alternative dual-tracer protocols to permit 5-class Ki/MR-AC for (ii) 18F-FDG-only data, with a streamlined simultaneous administration of 18F-FDG and 18F-NaF at 4:1 ratio (R4:1), or (iii) for 18F-FDG-only or both 18F-FDG and 18F-NaF dual-tracer data, by administering 18F-NaF 90 minutes after an equal 18F-FDG dosage (R1:1). The Ki-driven bone segmentation was validated against computed tomography (CT)-based segmentation in rabbits, followed by PET/MR validation on 108 vertebral bone and carotid wall regions in 16 human volunteers with and without prior indication of carotid atherosclerosis disease (CAD).ResultsIn rabbits, we observed similar (< 1.2% mean difference) vertebral bone 18F-NaF SUVmean scores when applying 5-class AC with Ki-segmented bone (5-class Ki/CT-AC) vs CT-segmented bone (5-class CT-AC) tissue. Considering the PET data corrected with continuous CT-AC maps as gold-standard, the percentage SUVmean bias was reduced by 17.6% (18F-NaF) and 15.4% (R4:1) with 5-class Ki/CT-AC vs 4-class CT-AC. In humans without prior CAD indication, we reported 17.7% and 20% higher 18F-NaF target-to-background ratio (TBR) at carotid bifurcations wall and vertebral bones, respectively, with 5- vs 4-class AC. In the R4:1 human cohort, the mean 18F-FDG:18F-NaF TBR increased by 12.2% at carotid bifurcations wall and 19.9% at vertebral bones. For the R1:1 cohort of subjects without CAD indication, mean TBR increased by 15.3% (18F-FDG) and 15.5% (18F-NaF) at carotid bifurcations and 21.6% (18F-FDG) and 22.5% (18F-NaF) at vertebral bones. Similar TBR enhancements were observed when applying the proposed AC method to human subjects with prior CAD indication.ConclusionsKi-driven bone segmentation and 5-class hybrid PET/MR-driven AC is feasible and can significantly enhance 18F-NaF and 18F-FDG contrast and quantification in bone tissues and carotid walls.

Project description:Neurodegenerative biomarkers support diagnosis and measurement of disease progression in the Alzheimer's disease (AD) continuum. 18F-Fluorodeoxyglucose Positron Emission Tomography (18F-FDG-PET), which measures glucose metabolism, is one of the most commonly used biomarkers of neurodegeneration, but is expensive and requires exposure to ionizing radiation. Arterial Spin Labeled (ASL) perfusion Magnetic Resonance Imaging (MRI) provides non invasive quantification of cerebral blood flow (CBF), which is believed to be tightly coupled to glucose metabolism. Here we aimed to compare the performances of ASL derived CBF and 18F-FDG-PET derived standardized uptake value ratio (SUVR) in discriminating patients with mild cognitive impairment (MCI) from older Controls. 2D pseudo continuous ASL and 18F-FDG-PET data with adequate scan quality from 50 MCI study participants (age=73.0 ± 7.0 years, 16 female) and 35 older controls (age=70.2 ± 6.9 years, 20 female), acquired in close temporal proximity, usually on the same day, were considered for this study. We assessed Control-patient group differences both at voxel level and within a priori regions of interest (ROIs). We also compared their area under receiver operating characteristic curves (AUC) with mean CBF or SUVR in a priori selected posterior cingulate cortex (PCC). CBF and 18F-FDG-PET showed abnormalities in similar areas, particularly in medial temporoparietal regions, consistent with the typically observed pattern of prodromal AD. The hypoperfusion pattern with relative CBF (obtained by normalizing voxel CBF values with mean CBF in putamen) was more localized than with absolute CBF. Pearson's correlation coefficients between the T-scores corresponding to the group-differences obtained with 18F-FDG-PET SUVR and absolute and relative ASL CBF were 0.46 and 0.43 (p<0.001), respectively. ROI analyses were also consistent, with the strongest differences observed in PCC (p<0.01). 18F-FDG-PET SUVR, absolute and relative CBF in the PCC ROI demonstrated moderate and similar discriminatory power in predicting MCI status with AUC of 0.71 ± 0.12, 0.77 ± 0.12 and 0.74 ± 0.13, respectively. In conclusion, ASL CBF may be a reasonable, less expensive and safer substitute for 18F-FDG-PET in clinical research.

Project description:BackgroundThe lack of visualization of the spinal cord hinders the evaluation of [18F]Fluoro-deoxy-glucose (FDG) uptake of the spinal cord in PET/CT. By exploiting the capability of MRI to precisely outline the spinal cord, we performed a retrospective study aimed to define normal pattern of spinal cord [18F]FDG uptake in PET/MRI.MethodsForty-one patients with lymphoma without clinical or MRI signs of spinal cord or bone marrow involvement underwent simultaneous PET and MRI acquisition using Siemens Biograph mMR after injection of 3.5 MBq/kg body weight of [18F]FDG for staging purposes. Using a custom-made software, we placed ROIs of 3 and 9 mm in diameter in the spinal cord, lumbar CSF, and vertebral marrow that were identified on MRI at 5 levels (C2, C5, T6, T12, and L3). The SUVmax, SUVmean, and the SUVmax and SUVmean normalized (NSUVmax and NSUVmean) to the liver were measured. For comparison, the same ROIs were placed in PET-CT images obtained immediately before the PET-MRI acquisition following the same tracer injection.ResultsOn PET/MRI using the 3 mm ROI, the following average (all level excluding L3) spinal cord median (1st and 3rd quartile) values were measured: SUVmean, 1.68 (1.39 and 1.83); SUVmax, 1.92 (1.60 and 2.14); NSUVmean, 1.18 (0.93 and 1.36); and NSUVmax, 1.27 (1.01 and 1.33). Using the 9 mm ROI, the corresponding values were SUVmean, 1.41 (1.25-1.55); SUVmax, 2.41 (2.08 and 2.61); NSUVmean, 0.93 (0.79 and 1.04); and NSUVmax, 1.28 (1.02 and 1.39). Using the 3 mm ROI, the highest values of PET-MRI SUVmax, SUVmean, NSUVmax, and NSUVmean were consistently observed at C5 and the lowest at T6. Using a 9 mm ROI, the highest values were consistently observed at C5 and the lowest at T12 or T6. The spinal cord [18F]FDG-uptake values correlated with the bone marrow uptake at the same level, especially in case of NSUVmax. Comparison with PET-CT data revealed that the average SUVmax and SUVmean of the spinal cord were similar in PET-MRI and PET-CT. However, the average NSUVmax and NSUVmean of the spinal cord were higher (range 21-47%) in PET-MRI than in PET-CT.ConclusionsUsing a whole-body protocol, we defined the maximum and mean [18F]FDG uptake of the normal spinal cord in PET/MRI. While the observed values show the expected longitudinal distribution, they appear to be higher than those measured in PET/CT. Normalization of the SUVmax and SUVmean of the spinal cord to the liver radiotracer uptake could help in multi-institutional comparisons and studies.

Project description:Knowledge of the within-subject variability of 18F-FDG PET/MRI measurements is necessary for proper interpretation of quantitative PET or MRI metrics in the context of therapeutic efficacy assessments with integrated PET/MRI scanners. The goal of this study was to determine the test-retest repeatability of these metrics on PET/MRI, with comparison to similar metrics acquired by PET/CT. Methods: This prospective study enrolled subjects with pathology-proven pelvic malignancies. Baseline imaging consisted of PET/CT immediately followed by PET/MRI, using a single 370-MBq 18F-FDG dose. Repeat imaging was performed within 7 d using an identical imaging protocol, with no oncologic therapy between sessions. PET imaging on both scanners consisted of a list-mode acquisition at a single pelvic station. The MRI consisted of 2-point Dixon imaging for attenuation correction, standard sequences for anatomic correlation, and diffusion-weighted imaging. PET data were statically reconstructed using various frame durations and minimizing uptake time differences between sessions. SUV metrics were extracted for both PET/CT and PET/MRI in each imaging session. Apparent diffusion coefficient (ADC) metrics were extracted for both PET/MRI sessions. Results: The study cohort consisted of 14 subjects (13 female, 1 male) with various pelvic cancers (11 cervical, 2 rectal, 1 endometrial). For SUVmax, the within-subject coefficient of variation (wCV) appeared higher for PET/CT (8.5%-12.8%) than PET/MRI (6.6%-8.7%) across all PET reconstructions, though with no significant repeatability differences (all P values ≥ 0.08) between modalities. For lean body mass-adjusted SUVpeak, the wCVs appeared similar for PET/CT (9.9%-11.5%) and PET/MRI (9.2%-11.3%) across all PET reconstructions, again with no significant repeatability differences (all P values ≥ 0.14) between modalities. For PET/MRI, the wCV for ADCmedian of 3.5% appeared lower than the wCVs for SUVmax (6.6%-8.7%) and SULpeak (9.2%-11.3%), though without significant repeatability differences (all P values ≥ 0.23). Conclusion: For solid tumors of the pelvis, the repeatability of the evaluated SUV and ADC metrics on 18F-FDG PET/MRI is both acceptably high and similar to previously published values for 18F-FDG PET/CT and MRI, supporting the use of 18F-FDG PET/MRI for quantitative oncologic treatment response assessments.

Project description:The present study examined the predictive values of amyloid PET, 18F-FDG PET, and nonimaging predictors (alone and in combination) for development of Alzheimer dementia (AD) in a large population of patients with mild cognitive impairment (MCI). Methods: The study included 319 patients with MCI from the Alzheimer Disease Neuroimaging Initiative database. In a derivation dataset (n = 159), the following Cox proportional-hazards models were constructed, each adjusted for age and sex: amyloid PET using 18F-florbetapir (pattern expression score of an amyloid-β AD conversion-related pattern, constructed by principle-components analysis); 18F-FDG PET (pattern expression score of a previously defined 18F-FDG-based AD conversion-related pattern, constructed by principle-components analysis); nonimaging (functional activities questionnaire, apolipoprotein E, and mini-mental state examination score); 18F-FDG PET + amyloid PET; amyloid PET + nonimaging; 18F-FDG PET + nonimaging; and amyloid PET + 18F-FDG PET + nonimaging. In a second step, the results of Cox regressions were applied to a validation dataset (n = 160) to stratify subjects according to the predicted conversion risk. Results: On the basis of the independent validation dataset, the 18F-FDG PET model yielded a significantly higher predictive value than the amyloid PET model. However, both were inferior to the nonimaging model and were significantly improved by the addition of nonimaging variables. The best prediction accuracy was reached by combining 18F-FDG PET, amyloid PET, and nonimaging variables. The combined model yielded 5-y free-of-conversion rates of 100%, 64%, and 24% for the low-, medium- and high-risk groups, respectively. Conclusion: 18F-FDG PET, amyloid PET, and nonimaging variables represent complementary predictors of conversion from MCI to AD. Especially in combination, they enable an accurate stratification of patients according to their conversion risks, which is of great interest for patient care and clinical trials.

Project description:ObjectiveTo compare the diagnostic performance of fecal biomarkers and 18F-fludeoxyglucose (18F-FDG) positron emmision tomography-MR (PET-MR) in the assessment of disease activity in patients with ulcerative colitis.MethodsThis study was conducted under the framework of a single-center clinical trial (clinicaltrials.gov [NCT03781284]). N = 50 participants were enrolled. Fecal samples were collected before bowel preparation. All patients underwent whole-body 18F-FDG PET-MR followed by ileocolonoscopy within 24 h. Diagnostic performance of five fecal biomarkers (calprotectin, lactoferrin, polymorphonuclear leukocyte elastase, S100A12 and eosinophil-derived neurotoxin), MR morphological parameters (MRmorph), diffusion-weighted imaging and PET in detecting active disease determined by Rachmilewitz endoscopic activity index (EAI) were evaluated and compared with each other. Correlations between fecal biomarkers, PET and endoscopy were calculated.ResultsAccording to EAI, n = 38 patients presented with endoscopically active disease (16 mild, 19 moderate and 3 severe). All five biomarkers, PET and MRmorph could differentiate endoscopically active disease from endoscopic remission without significant difference regarding their operating characteristics (accuracies between 0.673 for calprotectin and 0.898 for lactoferrin). In predicting endoscopically moderate to severe disease, PET showed the highest diagnostic performance (accuracy = 0.857) compared to calprotectin and lactoferrin (accuracy = 0.633 and 0.735). PET had also the strongest correlation with endoscopy (ρ = 0.685, p < 0.001), while within fecal biomarkers the levels of lactoferrin and eosinophil-derived neurotoxin correlated significantly with EAI (ρ = 0.423 and 0.528, both p < 0.05).ConclusionBoth fecal biomarkers and PET-MR were excellent non-invasive diagnostic tools in the assessment of disease activity in ulcerative colitis.Advances in knowledgeBoth fecal biomarkers and PET-MR parameters are able to predict endoscopically active disease with comparable diagnostic performance. PET had the highest correlation with endoscopy and outperformed fecal biomarkers in differentiating moderate to severe from mild disease.

Project description:Background and purposePET/MRI with 18F-FDG has demonstrated the advantages of simultaneous PET and MR imaging in head and neck cancer imaging, MRI allowing excellent soft-tissue contrast, while PET provides metabolic information. The aim of this study was to evaluate the added value of gadolinium contrast-enhanced sequences in the tumor delineation of head and neck cancers on 18F-FDG-PET/MR imaging.Materials and methodsConsecutive patients who underwent simultaneous head and neck 18F-FDG-PET/MR imaging staging or restaging followed by surgery were retrospectively included. Local tumor invasion and lymph node extension were assessed in 45 head and neck anatomic regions using 18F-FDG-PET/MR imaging by 2 rater groups (each one including a radiologist and a nuclear medicine physician). Two reading sessions were performed, one without contrast-enhanced sequences (using only T1WI, T2WI, and PET images) and a second with additional T1WI postcontrast sequences. The results were compared with the detailed histopathologic analysis, used as reference standard. The κ concordance coefficient between the reading sessions and sensitivity and specificity for each region were calculated.ResultsThirty patients were included. There was excellent agreement between the contrast-free and postgadolinium reading sessions in delineating precise tumor extension in the 45 anatomic regions studied (Cohen κ = 0.96, 95% CI = [0.94-0.97], P < .001). The diagnostic accuracy did not differ between contrast-free and postgadolinium reading sessions, being 0.97 for both groups and both reading sessions. For the 2 rater groups, there was good sensitivity for both contrast-free (0.83 and 0.85) and postgadolinium reading sessions (0.88 and 0.90, respectively). Moreover, there was excellent specificity (0.98) for both groups and reading sessions.ConclusionsGadolinium chelate contrast administration showed no added value for accurate characterization of head and neck primary tumor extension and could possibly be avoided in the PET/MR imaging head and neck workflow.

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¹⁸F-FDG PET Combined With MR Spectroscopy Elucidates the Progressive Metabolic Cerebral Alterations After Blast-Induced Mild Traumatic Brain Injury in Rats.

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18F-FDG PET Combined With MR Spectroscopy Elucidates the Progressive Metabolic Cerebral Alterations After Blast-Induced Mild Traumatic Brain Injury in Rats.

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OmicsDI is part of the ELIXIR infrastructure

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¹⁸F-FDG PET Combined With MR Spectroscopy Elucidates the Progressive Metabolic Cerebral Alterations After Blast-Induced Mild Traumatic Brain Injury in Rats.