Visualization of cranial giant cell arteritis with [18F]FDG PET/CT: A case report.

Giant cell arteritis is a form of large vessel vasculitis which can present with nonspecific symptoms, and if left untreated can cause significant morbidity and/or death. Early diagnosis and management are therefore paramount. The use of [18F]FDG PET/CT in the evaluation of giant cell arteritis has increased in recent years, with newer generation PET scanners capturing the historically elusive cranial vessel inflammation in active vasculitis. We present a case of giant cell arteritis which was suspected on conventional imaging modalities, and subsequently evaluated with [18F]FDG PET/CT which revealed marked vascular inflammation involving both cranial and other large vessels.

Unmasking hidden Merkel cell carcinoma recurrences: Three illustrative cases of patients with rising viral oncoprotein antibody levels and challenge of requiring multi-modal imaging to detect clinical disease.

Merkel cell carcinoma (MCC) is a neuroendocrine skin cancer with a high risk of recurrence and metastasis. Regular surveillance through physical exams and imaging studies is crucial for the timely detection of recurrences. MCC patients who produce antibodies to the Merkel cell polyomavirus oncoprotein may benefit from antibody testing in addition to routine imaging surveillance for the early detection of disease recurrence. The clinically available Anti MERKel cell panel (AMERK) is a sensitive tumor marker for Merkel cell polyomavirus positive MCC. Although AMERK is highly sensitive, imaging remains necessary to confirm the location of disease recurrence. MCC exhibits characteristic imaging features, making appropriate imaging modalities, and interpretation important for detection. We present 3 representative patient cases that highlight effective utilization of the AMERK test in addition to imaging for the early detection of MCC recurrence. The rise in the AMERK titer may occur before the disease reaches detectable size on computed tomography scans. Positron emission tomography (PET)-CT can serve as an alternative modality for the early detection of disease. Even subtle abnormalities in 18F-FDG uptake may be significant if accompanied by an increased AMERK titer. Alternative imaging modalities, such as 68Ga-DOTATATE PET-CT and magnetic resonance imaging, can be useful in revealing clinically occult disease in MCC patients. In summary, the AMERK antibody test, alongside imaging, enhances sensitivity in detecting recurrence. By combining these strategies of blood test and imaging, healthcare professionals can identify early signs of MCC recurrence, leading to prompt interventions and improved patient outcomes.

Nodular pulmonary amyloidosis diagnosed by ultrasound-guided percutaneous needle biopsy.

Pulmonary amyloidosis is characterized by extracellular deposition of fibrous protein called amyloid in the lungs and has three subtypes: nodular, diffuse, and tracheobronchial amyloidosis. Pulmonary nodular amyloidosis can mimic other lung diseases including infectious diseases, metastatic lung tumors, sarcoidosis, and pulmonary hyalinizing granuloma. A biopsy of the lesion is essential for a definitive diagnosis. Herein, we report the case of a 66-year-old man who presented for shortness of breath on exertion and was diagnosed with nodular pulmonary amyloidosis on ultrasound-guided percutaneous needle biopsy. A chest X-ray and computed tomography (CT) revealed bilateral slowly growing multiple calcified pulmonary nodules and cavities. Malignancy was suspected based on 18F-fluoro-deoxyglucose (18F-FDG) positron emission tomography/CT (PET/CT) images. An ultrasound-guided percutaneous needle biopsy was performed, and histopathologic examination of the lesion confirmed nodular pulmonary amyloidosis. This case highlights the importance of considering nodular pulmonary amyloidosis in the differential diagnosis of pulmonary nodules with increased uptake of 18F-FDG on PET/CT and the utility of ultrasound-guided needle biopsy in the definitive diagnosis.

Prevalence and clinical significance in our setting of incidental uptake in the thyroid gland found on 18F-fluordeoxyglucose positron emission tomography-computed tomography (PET-CT).

INTRODUCTION: The expanding use of 18F-fluorodeoxyglucose (FDG) positron emission tomography-computed tomography (PET-CT) has resulted in an increased frequency of incidentally discovered areas of FDG uptake within the thyroid gland. In these incidentalomas, high malignancy rates are reported. The study aimed, on the one hand, to determine the prevalence in our setting of thyroid incidentalomas in patients with no previous history of thyroid cancer undergoing an FDG PET-CT as well as the risk of malignancy and, on the other hand, to evaluate the usefulness of the maximum standard uptake value (SUVmax) for detecting thyroid cancer. MATERIAL AND METHODS: The FDG PET-CT scans performed at our hospital between June 2013 and December 2020 were retrospectively reviewed. In those incidentalomas with sufficient additional investigation, a diagnosis of benign or malignant was established based on the complementary tests. RESULTS: From the 21,594 PET-CT scans performed, 398 (1.8%) patients had an incidental FDG uptake, either focal (n=324) or diffuse (n=74). Among incidentalomas with further investigation, the rate of malignancy was higher in patients with focal FDG uptake than in those with diffuse uptake (26.5% versus 4%, respectively, p<0.05). The SUVmax value was significantly lower in benign focal lesions (5.7 [range: 2.3-66] than in malignant ones 10.6 [range: 3.1-51.2]; p<0.05). Nearly a quarter of malignant diagnoses (23.3%) were related to potentially aggressive tumours. CONCLUSION: The high rate of malignant tumours found among PET-CT incidentalomas and the high proportion of aggressive tumours demonstrate the need for a standardised approach in the investigation of incidental focal FDG uptake in the thyroid gland.

Deep Brain Stimulation in the Subthalamic Nucleus Can Improve Skilled Forelimb Movements and Retune Dynamics of Striatal Networks in a Rat Stroke Model.

Recovery of upper limb (UL) impairment after stroke is limited in stroke survivors. Since stroke can be considered as a network disorder, neuromodulation may be an approach to improve UL motor dysfunction. Here, we evaluated the effect of high-frequency stimulation (HFS) of the subthalamic nucleus (STN) in rats on forelimb grasping using the single-pellet reaching (SPR) test after stroke and determined costimulated brain regions during STN-HFS using 2-[18F]Fluoro-2-deoxyglucose-([18F]FDG)-positron emission tomography (PET). After a 4-week training of SPR, photothrombotic stroke was induced in the sensorimotor cortex of the dominant hemisphere. Thereafter, an electrode was implanted in the STN ipsilateral to the infarction, followed by a continuous STN-HFS or sham stimulation for 7 days. On postinterventional day 2 and 7, an SPR test was performed during STN-HFS. Success rate of grasping was compared between these two time points. [18F]FDG-PET was conducted on day 2 and 3 after stroke, without and with STN-HFS, respectively. STN-HFS resulted in a significant improvement of SPR compared to sham stimulation. During STN-HFS, a significantly higher [18F]FDG-uptake was observed in the corticosubthalamic/pallidosubthalamic circuit, particularly ipsilateral to the stimulated side. Additionally, STN-HFS led to an increased glucose metabolism within the brainstem. These data demonstrate that STN-HFS supports rehabilitation of skilled forelimb movements, probably by retuning dysfunctional motor centers within the cerebral network.

Dynamic alteration in SULmax predicts early pathological tumor response and short-term prognosis in non-small cell lung cancer treated with neoadjuvant immunochemotherapy.

Introduction: Biomarkers predicting tumor response to neoadjuvant immunochemotherapy in non-small cell lung cancer (NSCLC) are still lacking despite great efforts. We aimed to assess the effectiveness of the immune PET Response Criteria in Solid Tumors via SULmax (iPERCIST-max) in predicting tumor response to neoadjuvant immunochemotherapy and short-term survival in locally advanced NSCLC. Methods: In this prospective cohort study, we calculated SULmax, SULpeak, metabolic tumor volume (MTV), total lesion glycolysis (TLG) and their dynamic percentage changes in a training cohort. We then investigated the correlation between alterations in these parameters and pathological tumor responses. Subsequently, iPERCIST-max defined by the proportional changes in the SULmax response (△SULmax%) was constructed and internally validated using a time-dependent receiver operating characteristic (ROC) curve and the area under the curve (AUC) value. A prospective cohort from the Sun Yat-Sen University Cancer Center (SYSUCC) was also included for external validation. The relationship between the iPERCIST-max responsiveness and event-free survival in the training cohort was also investigated. Results: Fifty-five patients with NSCLC were included in this study from May 2019 to December 2021. Significant alterations in post-treatment SULmax (p < 0.001), SULpeak (p < 0.001), SULmean (p < 0.001), MTV (p < 0.001), TLG (p < 0.001), and tumor size (p < 0.001) were observed compared to baseline values. Significant differences in SULpeak, SULmax, and SULmean between major pathological response (mPR) and non-mPR statuses were observed. The optimal cutoff values of the SULmax response rate were -70.0% and -88.0% using the X-tile software. The univariate and multivariate binary logistic regression showed that iPERCIST-max is the only significant key predictor for mPR status [OR = 84.0, 95% confidence interval (CI): 7.84-900.12, p < 0.001]. The AUC value for iPERCIST-max was 0.896 (95% CI: 0.776-1.000, p < 0.001). Further, external validation showed that the AUC value for iPERCIST-max in the SYSUCC cohort was 0.889 (95% CI: 0.698-1.000, p = 0.05). Significantly better event-free survival (EFS) in iPERCIST-max responsive disease (31.5 months, 95% CI 27.9-35.1) than that in iPERCIST-max unresponsive disease (22.2 months, 95% CI: 17.3-27.1 months, p = 0.024) was observed. Conclusion: iPERCIST-max could better predict both early pathological tumor response and short-term prognosis of NSCLC treated with neoadjuvant immunochemotherapy than commonly used criteria. Furthermore, large-scale prospective studies are required to confirm the generalizability of our findings.

PET-Uptake in Liver Metastases as Method to Predict Tumor Biological Behavior in Patients Transplanted for Colorectal Liver Metastases Developing Lung Recurrence.

The objective of the study was to determine the impact of PET uptake on liver metastases on overall survival (OS) after resection of pulmonary metastases in patients who had received liver transplantation (LT) due to unresectable colorectal liver-only metastases. Resection of pulmonary colorectal metastases is controversial. Some hospitals offer this treatment to selected patients, whereas other hospitals do not perform the procedure in colorectal cancer patients who develop pulmonary metastases. All patients included in the LT studies who developed pulmonary metastases as first site of relapse, and had resection of these as first treatment, were included in this report. Metabolic tumor volume (MTV) in liver was derived from the pre-transplant PET examinations. OS from time of resection was calculated by the Kaplan−Meier method. Patients with low MTV (<70 cm3) had significantly longer OS from time of resection of pulmonary metastases compared to patients with high MTV (>70 cm3). Patients with low MTV in the liver had 10-year OS from time of pulmonary resections of 86%. Liver MTV values from pre-transplant PET examinations may predict long OS in colorectal cancer patients with a resection of pulmonary metastases developing after LT. Thus, in selected colorectal cancer patients developing pulmonary metastases resection of these metastases should be the treatment of choice.

Hidden in Plain Sight: Discovering Giant Cell Aortopathy During Surgical Mitral Valve Repair.

Giant cell arteritis (GCA) is an inflammatory cranial and/or extracranial vasculitis. Although cranial GCA is widely recognized, extracranial GCA is underdiagnosed because of its nonspecific and atypical presentations. We report a case of asymptomatic extracranial GCA with ascending thoracic aortopathy discovered incidentally during surgical mitral valve repair. (Level of Difficulty: Intermediate.).

Tissue Fraction Correction and Visual Analysis Increase Diagnostic Sensitivity in Predicting Malignancy of Ground-Glass Nodules on [18F]FDG PET/CT: A Bicenter Retrospective Study.

We investigated the role of [18F]FDG positron emission tomography/computed tomography (PET/CT) in evaluating ground-glass nodules (GGNs) by visual analysis and tissue fraction correction. A total of 40 pathologically confirmed ≥1 cm GGNs were evaluated visually and semiquantitatively. [18F]FDG uptake of GGN distinct from background lung activity was considered positive in visual analysis. In semiquantitative analysis, we performed tissue fraction correction for the maximum standardized uptake value (SUVmax) of GGN. Of the 40 GGNs, 25 (63%) were adenocarcinomas, 9 (23%) were minimally invasive adenocarcinomas (MIAs), and 6 (15%) were adenocarcinomas in situ (AIS). On visual analysis, adenocarcinoma showed the highest positivity rate among the three pathological groups (88%, 44%, and 17%, respectively). Both SUVmax and tissue-fraction−corrected SUVmax (SUVmaxTF) were in the order of adenocarcinoma > MIA > AIS (p = 0.033 and 0.018, respectively). SUVmaxTF was significantly higher than SUVmax before correction (2.4 [1.9−3.0] vs. 1.3 [0.8−1.8], p < 0.001). When using a cutoff value of 2.5, the positivity rate of GGNs was significantly higher in SUVmaxTF than in SUVmax (50% vs. 5%, p < 0.001). The diagnostic sensitivity of [18F]FDG PET/CT in predicting the malignancy of lung GGN was improved by tissue fraction correction and visual analysis.

Targeting whole body metabolism and mitochondrial bioenergetics in the drug development for Alzheimer's disease.

Aging is by far the most prominent risk factor for Alzheimer's disease (AD), and both aging and AD are associated with apparent metabolic alterations. As developing effective therapeutic interventions to treat AD is clearly in urgent need, the impact of modulating whole-body and intracellular metabolism in preclinical models and in human patients, on disease pathogenesis, have been explored. There is also an increasing awareness of differential risk and potential targeting strategies related to biological sex, microbiome, and circadian regulation. As a major part of intracellular metabolism, mitochondrial bioenergetics, mitochondrial quality-control mechanisms, and mitochondria-linked inflammatory responses have been considered for AD therapeutic interventions. This review summarizes and highlights these efforts.

18F-FDG-PET correlates of aging and disease course in ALS as revealed by distinct PVC approaches.

PURPOSE: The partial volume effect (PVE) complicates PET studies of neurodegenerative diseases, since a decreased 18F-FDG retention might be influenced by atrophy-related changes of cortical regions. Multiple partial volume correction (PVC) methods have been therefore developed, but their application in amyotrophic lateral sclerosis (ALS) is still rare. Additionally, even if metabolic changes have been established in ALS, no study yet has investigated how these may be influenced by aging and disease course. The aim of the present study was therefore to apply and compare multiple PVC approaches to explore aging and disease course-related hypometabolism in ALS. METHODS: PET and MRI data from 15 ALS patients were analyzed using PETSurfer to implement 4 distinct PVC methods: noPVC, Meltzer (MZ), Müller-Gärtner (MG) and Symmetric Geometric Transfer Matrix (SGTM). For each method and Region of Interest (ROI), the 18F-FDG value was regressed against subject age and disease duration. RESULTS: MG/SGTM application almost halved the number of regions showing a significant age-related hypometabolism, while the same effect was not observed for disease course, where only the distribution of identified regions varied. Three distinct patterns emerged: regions showing a significant age/disease course-related effect across all the different methods, regions yielding significance only with MG/SGTM application, and regions maintaining significance only with noPVC/MZ application. CONCLUSIONS: Significant changes in the distribution of aging and disease course-related hypometabolism were observed when the effect of the underlying structural status was considered, supporting the need for investigate the impact of PVE on PET-assessed metabolic changes in clinical and research settings.

Changes of cerebral network activity after invasive stimulation of the mesencephalic locomotor region in a rat stroke model.

Motor deficits after stroke reflect both, focal lesion and network alterations in brain regions distant from infarction. This remote network dysfunction may be caused by aberrant signals from cortical motor regions travelling via mesencephalic locomotor region (MLR) to other locomotor circuits. A method for modulating disturbed network activity is deep brain stimulation. Recently, we have shown that high frequency stimulation (HFS) of the MLR in rats has restored gait impairment after photothrombotic stroke (PTS). However, it remains elusive which cerebral regions are involved by MLR-stimulation and contribute to the improvement of locomotion. Seventeen male Wistar rats underwent photothrombotic stroke of the right sensorimotor cortex and implantation of a microelectrode into the right MLR. 2-[18F]Fluoro-2-deoxyglucose ([18F]FDG)-positron emission tomography (PET) was conducted before stroke and thereafter, on day 2 and 3 after stroke, without and with MLR-HFS, respectively. [18F]FDG-PET imaging analyses yielded a reduced glucose metabolism in the right cortico-striatal thalamic loop after PTS compared to the state before intervention. When MLR-HFS was applied after PTS, animals exhibited a significantly higher uptake of [18F]FDG in the right but not in the left cortico-striatal thalamic loop. Furthermore, MLR-HFS resulted in an elevated glucose metabolism of right-sided association cortices related to the ipsilateral sensorimotor cortex. These data support the concept of diaschisis i.e., of dysfunctional brain areas distant to a focal lesion and suggests that MLR-HFS can reverse remote network effects following PTS in rats which otherwise may result in chronic motor symptoms.

FDG-PET patterns associated with ideomotor apraxia and imitation apraxia in patients with corticobasal syndrome.

INTRODUCTION: Apraxia is a core clinical feature of corticobasal syndrome (CBS). Among the subtypes of apraxia, ideomotor and imitation apraxia are frequently found in CBS. However, little is known about the brain networks that are characteristic of each apraxia subtype or their clinical implication. In this study, we used 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) to explore the specific patterns of glucose hypometabolism that are characteristic of apraxia subtypes by focusing on ideomotor and imitation apraxia. METHODS: We compared the areas of glucose hypometabolism in the brains of 52 patients with CBS and 13 healthy controls, both as a whole and according to apraxia subtypes. In addition, we investigated the relationship between the apraxia subtypes and the clinical phenotype of CBS. RESULTS: In patients with CBS, common hypometabolism was observed in the frontal gyrus, precentral gyrus and caudate regardless of apraxia subtypes. In particular, ideomotor apraxia was associated with hypometabolism in the angular gyrus, while imitation apraxia was associated with hypometabolism in the posterior part including the postcentral gyrus, precuneus, and posterior cingulate gyrus. Patients who showed both ideomotor and imitation apraxia were more likely to show the typical features of CBS and progressive supranuclear palsy compared with patients showing only one type of apraxia. CONCLUSION: Group comparison analysis using FDG-PET revealed distinct pathways of ideomotor and imitation apraxia in CBS. These findings add to our understanding of the brain networks underlying apraxia in association with the clinical features of CBS.

Esophageal Cancer: Tumor-Node-Metastasis Staging.

Esophageal cancer is an uncommon malignancy that ranks sixth in terms of mortality worldwide. Squamous cell carcinoma is the predominant histologic subtype worldwide whereas adenocarcinoma represents the majority of cases in North America, Australia, and Europe. Esophageal cancer is staged using the American Joint Committee on Cancer and the International Union for Cancer Control TNM system and has separate classifications for the clinical, pathologic, and postneoadjuvant pathologic stage groups. The determination of clinical TNM is based on complementary imaging modalities, including esophagogastroduodenoscopy/endoscopic ultrasound; endoscopic ultrasound-fine-needle aspiration; computed tomography of the chest, abdomen, and pelvis; and fluorodeoxyglucose PET/computed tomography.

Rare Presentation of Radiation-induced Sarcoma Detected on F-18 FDG Positron Emission Tomography/Computed Tomography in a Treated Case of Giant Cell Tumor.

Giant cell tumors (GCTs) are benign bone lesions which are treated with curettage and bone grafting. Infrequently, GCTs show local site recurrences which are then treated with either surgical excision or radiation therapy. Radiation-induced sarcoma is rarely seen as a late complication of radiation therapy which needs to be differentiated from recurrent GCT. We report one such rare case of radiation-induced sarcoma detected on Flourine-18 fluorodeoxyglucose (18F FDG) positron emission tomography/computed tomography in a 40-year-old male who was treated with radiation therapy for recurrent GCT 9 years ago.

Downregulated GPR30 expression in the epileptogenic foci of female patients with focal cortical dysplasia type IIb and tuberous sclerosis complex is correlated with 18 F-FDG PET-CT values.

Focal cortical dysplasia type IIb (FCDIIb) and tuberous sclerosis complex (TSC) are typical causes of developmental delay and refractory epilepsy. G-protein-coupled receptor 30 (GPR30) is a specific estrogen receptor that is critical in neurodevelopment, neuroinflammation, and neuronal excitability, suggesting that it plays a potential role in the epilepsy of patients with FCDIIb and TSC. Therefore, we investigated the role of GPR30 in patients with FCDIIb and TSC. We found that the expression of GPR30 and its downstream protein kinase A (PKA) pathway were decreased and negatively correlated with seizure frequency in female patients with FCDIIb and TSC, but not in male patients. GPR30 was widely distributed in neurons, astrocytes, and microglia, and its downregulation was especially notable in microglia. The GPR30 agonist G-1 increased the expression of PKA and p-PKA in cultured cortical neurons, and the GPR30 antagonist G-15 exhibited the opposite effects of G-1. The NF-κB signaling pathway was also activated in the specimens of female patients with FCDIIb and TSC, and was regulated by G-1 and G-15 in cultured cortical neurons. We also found that GPR30 regulated cortical neuronal excitability by altering the frequency of spontaneous excitatory postsynaptic currents and the expression of NR2A/B. Further, the relationship between GPR30 and glycometabolism was evaluated by analyzing the correlations between GPR30 and 18 F-FDG PET-CT values (standardized uptake values, SUVs). Positive correlations between GPR30 and SUVs were found in female patients, but not in male patients. Intriguingly, GPR30 expression and SUVs were significantly decreased in the epileptogenic tubers of female TSC patients, and ROC curves indicated that SUVs could predict the localization of epileptogenic tubers. Taken together, our results suggest a potential protective effect of GPR30 in the epileptogenesis of female patients with FCDIIb and TSC.

Large vessel vasculitis and the rising role of FDG PET-CT: A case report and review of literature.

Giant cell arteritis (GCA) is a rare form of large and medium vessel vasculitis affecting about 20 cases per 100,000 persons older than the age of 50 years. GCA results in inflammation and constriction of the temporal arteries, cranial arteries, the aorta, and its major branches. Patients often present with vague constitutional symptoms and fever of unknown origin. GCA is a medical emergency requiring prompt diagnosis and early treatment with glucocorticoids which is essential to avoid irreversible end organ damage such as loss of vision, stroke and aneurysm formation. We report a case of a 63-year-old male patient presenting to our healthcare facility with sudden loss of vision and an ischemic brain infarct to be finally diagnosed as a case of giant cell arteritis with positron emission tomography-computed tomography imaging used to evaluate the full extent of the involved vasculature. Diagnostic imaging with FDG positron emission tomography-computed tomography can play a crucial role in the diagnosis, evaluation of the full burden of the disease and follow up to the response of therapy.

Fluorodeoxyglucose positron emission tomography/computed tomography identifying pericardial metastasis from early-stage p16-positive oropharyngeal cancer.

Pericardial metastasis from HPV-positive oropharyngeal squamous cell carcinoma (OPSCC) without local recurrence is extremely rare. We report about a 69-year-old man exhibiting pericardial metastasis on positron emission tomography/computed tomography (PET/CT). There are currently no reports on the use of PET/CT in patients with pericardial metastasis from p16-positive OPSCCs.