Longitudinal voxel-based FDG PET assessment of chemotherapy effects on brain metabolism in lung cancer.

Animal studies have shown that a course of electroconvulsive shock (ECS) leads to a significant reduction in glucose metabolism in rat brains 1 day after the last ECS. In humans, of the two positron emission tomography (PET) studies that assessed the effects of a course of electroconvulsive therapy (ECT) on brain glucose metabolism in depressed patients, one reported no change while the other found a trend for reduction in glucose metabolism in frontal cortical region 24 hours after last ECT. The changes in glucose metabolism detected 24 hours after the last ECS/ECT treatment might simply be due to subacute effects of a seizure. We hypothesized that the changes in brain metabolism that persist 1 week after a course of ECT are more likely to underlie the therapeutic effects of ECT. We, therefore, investigated the effects of a course of ECT on brain glucose metabolism 1 week after last ECT by using PET and [18F]fluorodeoxyglucose (FDG). Six patients who met DSM-IV criteria for a diagnosis of major depressive disorder (unipolar), and were referred for ECT as the clinically indicated treatment were recruited. They underwent two PET scans, one prior to first ECT and the second a week after last ECT. The number of ECT treatments subjects received ranged from 8 to 12 with a mean of 11. Five out of six patients responded to the ECT treatment. Cerebral metabolic rates for glucose were slightly lower in most regions post treatment compared with pretreatment but the differences were not statistically significant. Similarly, there was no significant correlation between changes in regional cerebral metabolic rates for glucose (rCMRglc) and changes in Hamilton Depression Rating Scale (HAM-D 21-item) scores. Our results might suggest that rCMRglc rates are not altered 1 week after a therapeutic course of ECT in depressed patients. Further studies using new generation PET scanners, which have a higher resolution, in larger numbers of depressed patients, are clearly needed before firm conclusions can be drawn.

Obsessive-compulsive disorder (OCD) is a chronic neural psychological condition. Its pathogenesis is not yet completely understood. This current research used fluorine-18 fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) imaging to examine the changes in brain glucose metabolism in patients with OCD during the course of treatment, and analyzed its relationship with clinical efficacy. A total of 23 patients with OCD were enrolled and divided into case group 1, consisting of patients who received no drug treatment or those who recently stopped drug treatment for more than five half-life periods (OCD1 group, N=10), and case group 2, consisting of patients who were receiving drug treatment before enrollment (OCD2 group, N=13). Ten healthy volunteers were selected as controls. All patients and healthy controls were subjected to head PET-computed tomography (CT) examination. Seven patients in case group 2 underwent scanning again after 3 months of drug treatment, namely, case group 3 (OCD3 group, N=7). Statistical Parametric Mapping (SPM) 8 software was used to analyze the PET-CT results. OCD patients had abnormally enhanced glucose metabolism in the medium orbito-frontal region of the brain, and abnormally reduced glucose metabolism in brain areas including the insula, caudate nucleus, and middle temporal gyrus. No changes in brain glucose metabolism related to curative effect was found. In OCD patients, abnormal brain function may not only be limited to the usual cortico-striato-thalamo-cortical (CSTC) loop model, but may involve a wide range of brain regions simultaneously.

Study DesignA prospective study.PurposeTo assess postoperative changes in cerebral glucose metabolism in anxiety patients with lumbar spinal stenosis (SS).Overview of LiteratureAlthough an association between preoperative anxiety and abnormal cerebral glucose metabolismmay exist, only a limited number of studies using F-18 fluorodeoxyglucose positron emission tomography (FDG PET) haveevaluated preoperative to postoperative changes in cerebral glucose metabolism in SS patients in detail.MethodsThe present study was designed to assess preoperative to postoperative changes in cerebral glucose metabolism in anxiety patients with SS. F-18 FDG PET with statistical parametric mapping analyses was used to compare preoperative and postoperative regional brain glucose metabolism in 18 SS patients.ResultsF-18 FDG PET scans showed postoperative activation of several brain clusters in gray matter. These included left parahippocampus, left cerebellar tonsil, left inferior semi-lunar lobule, and right cerebellar tonsil. Areas that were deactivated postoperatively were the right insula, left fusiform gyrus, left orbitofrontal cortex, left inferior frontal gyrus, left middle frontal gyrus, left precuneus, and left inferior frontal gyrus.ConclusionsSS patients with preoperative anxiety showed altered cerebral glucose metabolism at postoperative follow-up.

It remains unclear how brain metabolic activities transform in response to dopamine deficiency in the prodromal and early phases of Parkinson's disease (PD). To investigate the relationship between nigrostriatal dopaminergic denervation and brain glucose metabolism in patients with isolated rapid eye movement sleep behavior disorder (iRBD) and early PD. This cohort study included 28 patients with polysomnography-confirmed iRBD, 24 patients with de novo PD with probable rapid eye movement sleep behavior disorder (denovo PD), and 28 healthy controls (HCs) who underwent two positron emission tomography scans with 18 F-fluorodeoxyglucose (all participants) and 18 F-N-3-fluoropropyl-2β-carboxymethoxy-3β-(4-iodophenyl)-nortropane (except for one denovo PD patient and 15 HCs). We analyzed striatal and voxel-wise whole-brain glucose metabolism in relation to nigrostriatal dopaminergic integrity and comparatively investigated the whole-brain metabolic connectivity among the groups. We also assessed longitudinal metabolic changes against progressive dopaminergic denervation over 4 years in the iRBD group. From HCs to iRBD and finally to the denovo PD, dopaminergic integrity positively correlated with metabolic activity in the caudate, whereas a negative correlation was observed in the posterior putamen. In the iRBD group, there was a metabolic increase in the inferior orbitofrontal cortex against putaminal dopaminergic denervation at baseline, but negative correlations were newly observed in the superior orbitofrontal cortex and superior frontal gyrus at the 4-year follow-up. The denovo PD group showed negative correlations in the cerebellum and fusiform gyrus. Intra- and inter-regional metabolic connectivities in the parieto-occipital cortices were enhanced in the iRBD group compared with the denovo PD and HC groups. In the iRBD group, overall metabolic connectivity was strengthened along with enhanced basal ganglia-frontal connection by advancing dopaminergic denervation. Our findings suggest diverse trajectories of metabolic responses associated with dopaminergic denervation between individual brain areas in the prodromal and early PD stages. © 2022 International Parkinson and Movement Disorder Society.

Background:Cerebral glucose metabolism changes are always observed in patients suffering from malignant tumors. This preliminary study aimed to investigate the brain glucose metabolism changes in patients with lung cancer of different histological types.Methods:One hundred and twenty patients with primary untreated lung cancer, who visited People's Hospital of Zhengzhou University from February 2012 to July 2013, were divided into three groups based on histological types confirmed by biopsy or surgical pathology, which included adenocarcinoma (52 cases), squamous cell carcinoma (43 cases), and small-cell carcinoma (25 cases). The whole body 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT) of these cases was retrospectively studied. The brain PET data of three groups were analyzed individually using statistical parametric maps (SPM) software, with 50 age-matched and gender-matched healthy controls for comparison.Results:The brain resting glucose metabolism in all three lung cancer groups showed regional cerebral metabolic reduction. The hypo-metabolic cerebral regions were mainly distributed at the left superior and middle frontal, bilateral superior and middle temporal and inferior and middle temporal gyrus. Besides, the hypo-metabolic regions were also found in the right inferior parietal lobule and hippocampus in the small-cell carcinoma group. The area of the total hypo-metabolic cerebral regions in the small-cell carcinoma group (total voxel value 3255) was larger than those in the adenocarcinoma group (total voxel value 1217) and squamous cell carcinoma group (total voxel value 1292).Conclusions:The brain resting glucose metabolism in patients with lung cancer shows regional cerebral metabolic reduction and the brain hypo-metabolic changes are related to the histological types of lung cancer.

Background: To investigate the effect of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) chemotherapy on brain glucose metabolism in patients with diffuse large B cell lymphoma (DLBCL). Methods: Seventy-two patients with newly diagnosed DLBCL underwent FDG PET/CT brain and whole-body scans at baseline (PET0), in the interim of chemotherapy (PET2), and at the end (PET6) of chemotherapy. All three brain scans of each patient were analyzed using statistical parametric mapping software. Results: Compared with the PET0 scan, the PET2 and PET6 scans revealed a significantly higher glucose metabolism throughout the whole brain, with the PET6 scan revealing a higher metabolism than the PET2 scan. Patients with a complete response (CR) displayed decreased glucose metabolism in the lingual gyrus and increased glucose metabolism in the pons after chemotherapy compared with the findings in patients with partial responses or progressive disease. Conclusions: Brain glucose metabolism was affected by R-CHOP treatment throughout the entire chemotherapy protocol.

BackgroundLittle is known about the effects of subphrenic radiotherapy on brain glucose metabolism in patients with cervical cancer (CC) after chemotherapy. This study aimed to explore the effects of radiotherapy, chemotherapy, and radiochemotherapy on brain glucose metabolism in patients with CC.MethodsA total of 237 CC patients who underwent 18F-fluorodeoxyglucose (18F-FDG) positron-emission tomography (PET)/computed tomography (CT) were included, consisting of 88 patients without treatment, 61 patients with radiotherapy, 24 patients with chemotherapy and 64 patients with radiochemotherapy. One-way analysis of variance (ANOVA) was used to explore the effects of chemotherapy, radiotherapy and radiochemotherapy factors on brain PET data in CC patients by using statistical parametric mapping (SPM).ResultsCompared to CC patients without treatment, hypometabolism in some frontal and temporal lobes and no hypermetabolic regions were observed in those with radiotherapy (PFWEc < 0.05), while no significant brain metabolic areas was found in those with chemotherapy. Some above hypometabolic regions identified in radiotherapy and some other hypometabolic regions were found in patients with radiochemotherapy relative to those without treatment (PFWEc < 0.05). In addition, comparing any two of the radiotherapy, chemotherapy and radiochemotherapy groups only found significantly altered brain metabolic regions located in the right lingual gyrus between the radiotherapy and chemotherapy groups (PFWEc < 0.05).ConclusionRadiotherapy might decrease metabolism in the temporal and frontal lobes in CC patients. Furthermore, chemotherapy and radiotherapy might synergistically decrease glucose metabolism in some frontotemporal regions of CC patients, which might indicate potential cognitive impairment and emotional disorders.

The Effect of Aromatase Inhibition on the Cognitive Function of Older Patients With Breast Cancer

We studied brain glucose metabolism in patients with Alzheimer's disease and age-matched controls in vivo by PET and assessed brain glucose utilization and the phosphorylation constant K3 for hexokinase. In addition we determined in vitro the binding of 2DG and measured its phosphorylation to 2DG-phosphate in cerebral microvessels obtained at autopsy from subjects with Alzheimer's disease and age-matched controls. In patients with Alzheimer's disease we found a marked decrease in the kinetic constant K3 for the hexokinase, and a marked decrease in the overall metabolism of glucose in our PET studies; in microvessels there was a marked decrease in the affinity of 2DG and a decrease in hexokinase activity. Alzheimer's disease may be related to a complex alteration in brain glucose metabolism.

Measuring 18F-FDG PET-detected brain glucose uptake provides reliable information on metabolic tissue abnormalities, cells dysfunction, and neurovascular changes after traumatic brain injury (TBI). We aimed to study the relationship between post-traumatic brain glucose metabolism and functional outcomes in the so far unexplored field of longitudinally 18F-FDG PET-monitored patients undergoing rehabilitation after moderate-to-severe TBI. Fourteen patients consecutively admitted to our unit in the post-acute phase after TBI underwent 18F-FDG-PET scans performed before and 6 months after inpatient rehabilitation program. The Glasgow Coma Scale (GCS) for neurological status, and the Functional Independence Measure (FIM) plus the Glasgow Outcome Scale-Extended (GOSE) scales for the rehabilitation outcome, were applied on admission and discharge. Voxel-wise analyses were performed, with the Statistical Parametric Mapping (SPM12) software, to investigate pre- vs. post-rehabilitation changes of brain metabolism, and their relationships with clinical indices. In the whole sample, 18F-FDG uptake significantly increased in the following five regions that were hypometabolic before rehabilitation: inferior frontal gyrus bilaterally, alongside right precentral gyrus, inferior parietal lobule, and cerebellum. However, only for the right precentral gyrus the median voxel peak-value at baseline resulted a significant predictor of both cognitive (FIM cognitive subscale, p = 0.012), and functional (GOS-E, p = 0.02; post- vs. pre-treatment GOS-E difference, p = 0.009) improvements. ROC curve analysis showed that a peak voxel-value of 1.7998 was the optimal cut-off for favorable rehabilitation outcome. Unfavorable functional outcomes were predicted by increased 18F-FDG uptake in the inferior frontal gyrus (GOS-E, p = 0.032) and precentral gyrus (FIM cognitive subscale, p = 0.017; GOS-E, p = 0.015). This proof-of-principle study enlightens the metabolic changes occurring in moderate-to-severe TBI course. Notably, such changes preferentially involve definite frontal brain areas regardless of TBI localization and entity. These findings pave the way for further studies with translational purposes.

To investigate the changes in cerebral glucose metabolism in patients with posttraumatic cognitive impairment after memantine therapy. We performed serial F-18 fluorodeoxyglucose positron emission tomography studies before and after memantine therapy (20 mg per day) on 17 patients with posttraumatic cognitive impairment using statistical parametric mapping analysis. In addition, covariance analysis was performed to identify regions, where changes in regional cerebral glucose metabolism correlated significantly with increased Mini-Mental Status Examination scores. Statistical parametric mapping analysis demonstrated that, compared with baseline, significantly increased cerebral glucose metabolism occurred in both inferior, middle and superior frontal gyri, both angular gyri, both precuneus, the right middle cingulum, the left inferior parietal lobule, the left fusiform gyrus, the left precentral gyrus, the left paracentral lobule, and the left lingual gyrus after memantine therapy (P (uncorrected) < 0.005). In contrast, cerebral glucose metabolism was significantly decreased in both cerebellum, the left thalamus, the left olfactory, the right middle temporal gyrus, the right amygdala, and the right insula (P (uncorrected) < 0.005). In the correlation analysis, improvements in Mini-Mental Status Examination scores after memantine therapy were significantly associated with increased cerebral glucose metabolism in the inferior and middle frontal gyri and the inferior parietal lobule of the left hemisphere (P (corrected) < 0.0001). Our findings indicate that the prefrontal and the parietal association cortices may be the relevant structures for the pharmacological response to memantine therapy in patients with posttraumatic cognitive impairment.

This study compared brain glucose metabolism using FDG-PET in the caudate nucleus, putamen, globus pallidus, thalamus, and dorsolateral prefrontal cortex (DLPFC) among patients with Long COVID, patients with fatigue, people with multiple sclerosis (PwMS) patients with fatigue, and COVID recovered controls. PwMS exhibited greater hypometabolism compared to long COVID patients with fatigue and the COVID recovered control group in all studied brain areas except the globus pallidus (effect size range 0.7-1.5). The results showed no significant differences in glucose metabolism between patients with Long COVID and the COVID recovered control group in these regions. These findings suggest that long COVID fatigue may involve non-CNS systems, neurotransmitter imbalances, or psychological factors not captured by FDG-PET, while MS-related fatigue is associated with more severe frontal-striatal circuit dysfunction due to demyelination and neurodegeneration. Symmetrical standardized uptake values (SUVs) between hemispheres in all groups imply that fatigue in these conditions may be related to global or network-level alterations rather than hemisphere-specific changes. Future studies should employ fine-grained analysis methods, explore other brain regions, and control for confounding factors to better understand the pathophysiology of fatigue in MS and long COVID. Longitudinal studies tracking brain glucose metabolism in patients with Long COVID could provide insights into the evolution of metabolic patterns as the condition progresses.

Florbetapir (AV45) and fluorodeoxyglucose (FDG) PET imaging are valuable techniques to detect the amyloid-β (Aβ) load and brain glucose metabolism in patients with Alzheimer's disease (AD). The purpose of this study is to access the characteristics of Aβ load and FDG metabolism in brain for further investigating their relationships with cognitive impairment in AD patients. Twenty-seven patients with AD (average 70.6 years old, N = 13 male, N = 14 female) were enrolled in this study. These AD patients underwent the standard clinical assessment and received detailed imaging examinations of the nervous system by using Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MOCA), 18F-AV45, and 18F-FDG PET scans. Of 27 AD patients, 22 patients (81.5%) showed significantly increases in Aβ load and 26 patients (96.3%) had significantly reductions in FDG metabolism. The moderate AD patients had more brain areas of reduced FDG metabolism and more severe reductions in some regions compared to mild AD patients, with no differences in Aβ load observed. Moreover, the range and degree of reduced FDG metabolism in several regions were positively correlated with the total score of MMSE or MOCA, whereas the range of Aβ load did not. No correlation was found between the range of Aβ load and the range of reduced FDG metabolism in this study. The reduction in FDG metabolisms captured by 18F-FDG imaging can be used as a potential biomarker for AD diagnosis in the future. 18F-AV45 imaging did not present valuable evidence for evaluating AD patient in this study.

COVID-19 disease, caused by the SARS-CoV-2 virus, has significantly altered modern society and lifestyles. We investigated its impact on brain glucose metabolism by meta-analyzing existing studies that utilized 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) scans of the brain. We conducted a systematic search of MEDLINE and EMBASE databases from inception to August 2024 for English-language publications using the keywords "positron emission tomography", and "COVID-19". We included original research articles that reported changes in brain glucose metabolism following COVID-19 disease. ALE values from these studies were aggregated and tested against a null hypothesis that anticipated a random distribution of ALE values, which proved to be significantly higher than chance. We identified nine papers that met our inclusion criteria. Significant increases in brain glucose metabolism were noted in the left anterior cingulate gyrus, right thalamus, and brainstem. In children with COVID-19 disease, decreased glucose metabolism was observed in the right and left cerebellum, left amygdala/hippocampus, left anterior cingulate gyrus, and right amygdala. In adults with COVID-19 disease, decreased metabolism was seen in the right temporal lobe, brainstem (acute phase), left occipital lobe, left and right temporal lobe (chronic phase). In conclusion, COVID-19 disease impacts brain glucose metabolism, typically manifesting as areas of decreased metabolism in 18F-FDG PET scans, though increases are also observed. These changes in metabolism vary with the patient's age and the time elapsed between the diagnosis of COVID-19 disease and the PET scan.

Sleep deprivation PET correlations of Hamilton symptom improvement ratings with changes in relative glucose metabolism in patients with depression