FDG-PET Findings Research Articles

Immune-related [18F]FDG PET findings in patients undergoing checkpoint inhibitors treatment: correlation with clinical adverse events and prognostic implications

BackgroundDirect comparisons between [18F]FDG PET/CT findings and clinical occurrence of immune-related adverse events (irAEs) based on independent assessments of clinical and imaging features in patients receiving immune checkpoint inhibitors (ICIs) are missing. Our aim was to estimate sites, frequency, and timing of immune-related PET findings during ICIs treatment in patients with melanoma and NSCLC, and to assess their correlation with clinical irAEs. Prognostic implications of immune-related events were also investigated.MethodsFifty-one patients with melanoma (47%) or NSCLC (53%) undergoing multiple PET examinations during anti-PD1/PDL1 treatment were retrospectively included. Clinical irAEs were graded according to CTCAE v.5.0. Abnormal PET findings suggestive of immune activation were described by two readers blinded to the clinical data. Progression-free survival (PFS) and overall survival (OS) were analyzed with the Kaplan-Meier method in patients stratified according to the presence of irAEs, immune-related PET findings or both.ResultsTwenty-one patients showed clinical irAEs only (n = 6), immune-related PET findings only (n = 6), or both (n = 9). In patients whose imaging findings corresponded to clinical irAEs (n = 7), a positive correlation between SUVmax and the severity of the clinical event was observed (rs=0.763, p = 0.046). Clinical irAEs occurred more frequently in patients without macroscopic disease than in metastatic patients (55% vs. 23%, p = 0.039). Patients who developed clinical irAEs had a significantly longer PFS than patients who remained clinically asymptomatic, both in the overall cohort (p = 0.011) and in the subgroup of (n = 35) patients with metastatic disease (p = 0.019). The occurrence of immune-related PET findings significantly stratified PFS in the overall cohort (p = 0.040), and slightly missed statistical significance in patients with metastatic disease (p = 0.08). The best stratification of PFS was achieved when all patients who developed immune-related events, either clinically relevant or detected by PET only, were grouped together both in the overall cohort (p = 0.002) and in patients with metastatic disease (p = 0.004). In the whole sample, OS was longer in patients who developed any immune-related events (p = 0.032).ConclusionPatients with melanoma or NSCLC under ICI treatment can develop clinical irAEs, immune-related PET findings, or both. The occurrence of immune-related events has a prognostic impact. Combining clinical information with PET assessment improved outcome stratification.

68Ga]Ga-ABY-025 PET in HER2-positive breast cancer: Benefits and pitfalls in staging of axillary disease.

1035 Background: [68Ga]Ga-ABY-025 PET showed promising results in quantifying human epidermal growth factor receptor Type 2 (HER2) expression in breast cancer patients [1]. In this study we extend the findings from [68Ga]Ga-ABY-025 PET with data from both treatment-naïve patients and previously treated patients with recurrences, mimicking the clinical situation other sites might encounter when HER2-targeting imaging is made more widely available. The focus of this additional data analysis is on staging, potential pitfalls and changes in uptake patterns associated with previous treatments. Methods: [68Ga]Ga-ABY-025 PET and [18F]-FDG PET images from 50 women with biopsy confirmed HER2 positive breast cancer were examined. Each patient underwent both scans within 1 week. A follow-up [18F]-FDG PET was performed after 2 courses of HER2-targeted treatment to assess metabolic response. Results: Twelve out of 50 patients showed heterogeneous [68Ga]Ga-ABY-025 uptake. Three out of these 12 patients presented with a wider local spread that was only detectable using [68Ga]Ga-ABY-025 PET as distinct uptake in lymph nodes of 2-5 mm size. Based on the additional information from [68Ga]Ga-ABY-025 PET, restaging was evaluated in two of the three cases, both of which had lobular carcinoma, and resulted in modifications in treatment plans. Two patients who received COVID-19 vaccine closely before undergoing PET scans showed high uptake on [18F]-FDG PET in lymph nodes ipsilateral to the vaccine injection site, but not on [68Ga]Ga-ABY-025 PET. Additionally, the physiological [68Ga]Ga-ABY-025 uptake in thyroid gland and axillary sweat glands was inversely correlated with the number of previous treatments and was significantly more pronounced in treatment-naïve patients. Conclusions: [68Ga]Ga-ABY-025 PET provided additional information that, in conjunction with [18F]-FDG PET findings, might help in accurate staging, particularly in cases with very small lymph node metastases. It also helped reduce false positive results as [68Ga]Ga-ABY-025 uptake was so far not seen in any benign inflammatory lesions. Physiological uptake can be seen in thyroid and apocrine glandular tissues but gradually disappear with subsequent HER2-targeted therapies. 1,Alhuseinalkhudhur, A. et al. J Nucl Med, 2023 64(9): p. 1364-1370. Clinical trial information: NCT03655353 .

18F]FDG PET and CT findings at therapy completion of pulmonary tuberculosis: comparison between HIV-positive and HIV-negative patients and impact on treatment response assessment

Abstract Background [18F]FDG-PET/CT is a sensitive non-invasive tool for assessing treatment response in patients with pulmonary tuberculosis. The data on the performance of [18F]FDG-PET/CT for response assessment among patients infected with the human immunodeficiency virus (HIV) is limited. Here, we investigated the differences between PET and CT lung findings on end-of-treatment [18F]FDG-PET/CT among HIV-positive versus HIV-negative patients who completed anti-tuberculous therapy for pulmonary tuberculosis. Methods Patients who completed anti-tuberculous therapy for pulmonary tuberculosis and declared cured based on negative clinical and laboratory assessments for active pulmonary tuberculosis were prospectively recruited to undergo [18F]FDG-PET/CT. Patients were classified as having residual metabolic activity if PET metabolic activity was demonstrated in the lung parenchyma or complete metabolic response if there was no abnormally increased [18F]FDG avidity in the lungs and compared the CT features. We identified 10 CT lung changes, five were associated with active pulmonary tuberculosis (nodules, micronodules in tree-in-bud pattern, consolidation, pleural effusion, and [18F]FDG-avid mediastinal/hilar lymphadenopathy) and the rest were associated with inactive sequelae of prior pulmonary tuberculosis (cysts, cavities, fibrosis, bronchiectasis, and calcifications and compared their incidence between HIV-positive and HIV-negative patients. Results Seventy-five patients were included with a mean age of 36.09 ± 10.49 years. There were fifty HIV-positive patients, all of whom were on antiretroviral therapy and with a median CD4 + T-cell of 255 cells/µL (IQR: 147–488). Fifteen HIV-positive patients had detectable HIV viremia with a median viral load of 12,497 copies/mL (IQR: 158–38,841). There was a significant difference in the incidence of residual metabolic activity and complete metabolic response between HIV-positive and HIV-negative patients. (P = 0.003) HIV-positive patients were more likely to have [18F]FDG-avid lymphadenopathy and HIV-negative patients had a higher incidence of cystic lung changes. The pattern of CT lung changes was otherwise not different between HIV-positive and HIV-negative patients. (P > 0.05) Conclusions The incidence of residual metabolic activity and complete metabolic response on end-of-treatment [18F]F-FDG-PET/CT are similar between HIV-positive and HIV-negative patients. The incidence of [18F]FDG-avid mediastinal/hilar lymphadenopathy is more prevalent among HIV-positive patients. The pattern of lung changes was largely similar between HIV-positive and HIV-negative patients, indicating that the presence of HIV coinfection may not influence the interpretation of end-of-treatment [18F]F-FDG-PET/CT obtained for pulmonary tuberculosis treatment response assessment.

Deep brain stimulation of the amygdala for treatment-resistant combat post-traumatic stress disorder: Long-term results

Deep brain stimulation (DBS) holds promise for neuropsychiatric conditions where imbalance in network activity contributes to symptoms. Treatment-resistant Combat post-traumatic stress disorder (TR-PTSD) is a highly morbid condition and 50% of PTSD sufferers fail to recover despite psychotherapy or pharmacotherapy. Reminder-triggered symptoms may arise from inadequate top-down ventromedial prefrontal cortex (vmPFC) control of amygdala reactivity. Here, we report long-term data on two TR-PTSD participants from an investigation utilizing high-frequency amygdala DBS. The two combat veterans were implanted bilaterally with quadripolar electrodes targeting the basolateral amygdala. Following a randomized staggered onset, patients received stimulation with adjustments based on PTSD symptom severity for four years while psychiatric and neuropsychiatric symptoms, neuropsychological performance, and electroencephalography were systematically monitored. Evaluation of vmPFC-Amygdala network engagement was assessed with 18FDG positron emission tomography (PET). CAPS-IV scores varied over time, but improved 55% from 119 at baseline to 53 at 4-year study endpoint in participant 1; and 44%, from 68 to 38 in participant 2. Thereafter, during 5 and 1.5 years of subsequent clinical care respectively, long-term bilateral amygdala DBS was associated with additional, clinically significant symptomatic and functional improvement. There were no serious stimulation-related adverse psychiatric, neuropsychiatric, neuropsychological, neurological, or neurosurgical effects. In one subject, symptomatic improvement was associated with an intensity-dependent reduction in amygdala theta frequency power. In our two participants, FDG-PET findings were inconclusive regarding the hypothesized mechanism of suppression of amygdala hyperactivity. Our findings encourage further research to confirm and extend our preliminary observations.

Neurological and Psychiatric Manifestations of Long COVID-19 and Their [18F]FDG PET Findings: A Review.

For more than two years, lingering sequalae of COVID-19 have been extensively investigated. Approximately 10% of individuals infected by COVID-19 have been found to experience long-term symptoms termed "long COVID-19". The neurological and psychiatric manifestations of long COVID-19 are of particular concern. While pathogenesis remains unclear, emerging imaging studies have begun to better elucidate certain pathological manifestation. Of specific interest is imaging with [18F]FDG PET which directly reflects cellular glycolysis often linked to metabolic and inflammatory processes. Seeking to understand the molecular basis of neurological features of long COVID-19, this review encompasses the most recent [18F]FDG PET literature in this area.

Brain FDG-PET findings in chimeric antigen receptor T-cell therapy neurotoxicity for diffuse large B-cell lymphoma.

Chimeric antigen receptor (CAR) T-cell therapy is potentially associated with treatment-related toxicities mainly consisting of cytokine release syndrome (CRS) and immune-effector cell-associated neurotoxicity syndrome (ICANS). We evaluated brain metabolic correlates of CRS with and without ICANS in diffuse large B-cell lymphoma patients treated with CAR-T. Twenty-one refractory DLCBLs underwent whole-body and brain [18 F]-fluorodeoxyglucose (FDG) PET before and 30days after treatment with CAR-T. Five patients did not develop inflammatory-related side effects, 11 patients developed CRS, while in 5 patients CRS evolved in ICANS. Baseline and post-CAR-T brain FDG-PET were compared with a local controls dataset to identify hypometabolic patterns both at single-patient and group levels (p<.05 after correction for family-wise error [FWE). Metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were computed on baseline FDG-PET and compared between patients' subgroups (t-test). ICANS showed an extended and bilateral hypometabolic pattern mainly involving the orbitofrontal cortex, frontal dorsolateral cortex, and anterior cingulate (p<.003 FWE-corrected). CRS without ICANS showed significant hypometabolism in less extended clusters mainly involving bilateral medial and lateral temporal lobes, posterior parietal lobes, anterior cingulate, and cerebellum (p<.002 FWE-corrected). When compared, ICANS showed a more prominent hypometabolism in the orbitofrontal and frontal dorsolateral cortex in both hemispheres than CRS (p<.002 FWE-corrected). Mean baseline MTV and TLG were significantly higher in ICANS than CRS (p<.02). Patients with ICANS are characterized by a frontolateral hypometabolic signature coherently with the hypothesis of ICANS as a predominant frontal syndrome and with the more prominent susceptibility of frontal lobes to cytokine-induced inflammation.

68Ga-FAPI-46 PET for cancer imaging: A prospective single-arm clinical trial.

3064 Background: Fibroblast activation protein (FAP) is expressed at high levels on tumor associated fibroblasts. FAP-directed radioligand positron-emission-tomography (FAP-PET) is a novel diagnostic tool for cancer. However, we currently do not understand the diagnostic performance of FAP-PET as compared to standard FDG-PET. Here we aim to compare tumor detection by FDG- vs. FAP-PET with independent validation of discrepant findings. Methods: Patients with (a) proven or suspected malignancy, (b) longest tumor diameter &gt;1 cm, (c) intended surgery or biopsy, and (d) no prior external beam radiation or systemic tumor therapy within 3 months underwent FDG- and FAP-PET for tumor localization on subsequent days. Clinical reads were analyzed prospectively on a per-patient and per-region basis (local, locoregional nodal, distant organ or soft tissue, bone). Discrepant findings were validated as true vs. false positive by histopathology or image follow-up. Tracer uptake in tumor tissue was assessed by SUVmax. Results: In total n=100 patients (median 62 years, male/female n=68/32) underwent FDG- and FAP-PET. Five most frequent tumor entities and respective median FDG vs FAP uptake were RCC (n=19; SUVmax 8.4 vs. 7.1), sarcoma (n=18; 10.3 vs. 10.9), NSCLC (n=10; 12.4 vs. 13.7), lymphoma (n=9; 18.3 vs. 10.9), and PDAC (n=8; 4.1 vs. 7.3). On a per-patient basis, FDG- vs FAP-PET localized malignancy in n=93/94 patients. FDG- vs FAP-PET was concordant for the assessment of 362/400 (91%) regions. n=16/400 (4%) regions were negative on FDG- and positive on FAP-PET (88% true, 12% false positive). n=22/400 (6%) regions were negative on FAP- and positive on FDG-PET (57% true, 43% false positive). Two false positive FDG-PET findings were due to tracer uptake in reactive lymph nodes. There were no PET-related adverse events. Conclusions: In patients with various tumor entities, standard FDG- and novel FAP-PET localized tumor equally well. Additionally, FAP-PET was associated with a lower rate of false positive findings, especially in lymph node assessments. Clinical trial information: NCT05160051 . [Table: see text]

FDG-PET/CT and rest myocardial perfusion imaging to predict high-degree atrioventricular block recovery in cardiac sarcoidosis.

High-degree atrioventricular block (AVB) recovery in CS has been shown to be highly variable despite immunosuppressive treatment, with no reliable tool available to predict odds of reversibility. This study sought to evaluate the potential of combined fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) and resting myocardial perfusion imaging (rMPI) to predict reversibility of newly diagnosed high-grade AVB in cardiac sarcoidosis (CS). We performed a single-center, retrospective analysis of patients with CS presenting with high-grade AVB who underwent combined FDG-PET/CT and rMPI. The 2016 JCS and the 2014 HRS diagnostic criteria were used for the diagnosis of CS. Patients with a history of coronary artery disease or prior immunosuppressive treatment were excluded. Patients were divided into AVB recovery and non-recovery subgroups. CS disease staging was based on FDG-PET and rMPI findings: (Stage 0) normal FDG-PET and rMPI (Stage 1) positive FDG-PET and normal rMPI (Stage 2) positive FDG-PET with perfusion deficits on rMPI (Stage 3) normal FDG-PET with perfusion deficits on rMPI. Twenty-seven patients, including 13 demonstrating AVB recovery, were identified. Eleven out of fourteen (78.6%) patients presenting with stage 1 CS demonstrated AVB recovery. Stage 1 CS was significantly more present in the recovery group compared to the non-recovery group (84.6% vs 21.4%, P = .002). Eleven presented with stage 2 CS, with only 2 (18.2%) recovering AV nodal conduction. Stage 2 CS presented more frequently in the non-recovery group (64.3% vs 15.4%, P = .020). Combined FDG-PET and rMPI employed to stage CS disease presenting with high-degree AVB appears to have good performance for predicting likelihood of recovery.

Post-COVID-19 Brain [18F] FDG-PET Findings: A Retrospective Single-Center Study in the United States.

The pathophysiology of neurologic manifestations of postacute sequelae of Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) infection is not clearly understood. Our aim was to investigate brain metabolic activity on [18F] FDG-PET/CT scans in patients with a history of coronavirus disease 2019 (COVID-19) infection before imaging. This retrospective study included 45 patients who underwent [18F] FDG-PET/CT imaging for any reason and had, at least once, tested positive for COVID-19 at any time before imaging. Fifteen patients had available [18F] FDG-PET scans obtained under identical conditions before the infection. A group of 52 patients with melanoma or multiple myeloma who underwent [18F] FDG-PET/CT were used as controls. Whole-brain 2-sample t test analysis was performed using SPM software to identify clusters of hypo- and hypermetabolism and compare brain metabolic activity between patients with COVID-19 and controls. Paired sample t test comparison was also performed for 15 patients, and correlations between metabolic values of clusters and clinical data were measured. Compared with the control group, patients with a history of COVID-19 infection exhibited focal areas of hypometabolism in the bilateral frontal, parietal, occipital, and posterior temporal lobes and cerebellum (P = .05 uncorrected at the voxel level, family-wise error-corrected at the cluster level) that peaked during the first 2 months, improved to near-complete recovery around 6 months, and disappeared at 12 months. Hypermetabolism involving the brainstem, cerebellum, limbic structures, frontal cortex, and periventricular white matter was observed only at 2-6 months after infection. Older age, neurologic symptoms, and worse disease severity scores positively correlated with the metabolic changes. This study demonstrates a profile of time-dependent brain PET hypo- and hypermetabolism in patients with confirmed SARS-CoV-2 infection.

CAR t-cell therapy in BOlogNa-NEUrotoxicity TReatment and Assessment in Lymphoma (CARBON-NEUTRAL): proposed protocol and results from an Italian study.

To investigate neurotoxicity clinical and instrumental features, incidence, risk factors, and early and long-term prognosis in lymphoma patients who received CAR T-cell therapy. In this prospective study, consecutive refractory B-cell non-Hodgkin lymphoma patients who received CAR T-cell therapy were included. Patients were comprehensively evaluated (neurological examination, EEG, brain MRI, and neuropsychological test) before and after (two and twelve months) CAR T-cells. From the day of CAR T-cells infusion, patients underwent daily neurological examinations to monitor the development of neurotoxicity. Forty-six patients were included in the study. The median age was 56.5years, and 13 (28%) were females. Seventeen patients (37%) developed neurotoxicity, characterized by encephalopathy frequently associated with language disturbances (65%) and frontal lobe dysfunction (65%). EEG and brain FDG-PET findings also supported a predominant frontal lobe involvement. The median time at onset and duration were five and eight days, respectively. Baseline EEG abnormalities predicted ICANS development in the multivariable analysis (OR 4.771; CI 1.081-21.048; p = 0.039). Notably, CRS was invariably present before or concomitant with neurotoxicity, and all patients who exhibited severe CRS (grade ≥ 3) developed neurotoxicity. Serum inflammatory markers were significantly higher in patients who developed neurotoxicity. A complete neurological resolution following corticosteroids and anti-cytokines monoclonal antibodies was reached in all patients treated, except for one patient developing a fatal fulminant cerebral edema. All surviving patients completed the 1-year follow-up, and no long-term neurotoxicity was observed. In the first prospective Italian real-life study, we presented novel clinical and investigative insights into ICANS diagnosis, predictive factors, and prognosis.

Using illusions to understand hallucinations: differences in perceptual performances on illusory figures may underscore specific visuoperceptual impairments in Parkinson's disease.

Visual hallucinations are prevalent, potentially disabling symptoms of Parkinson's Disease. Multiple impairments in bottom-up sensory processing and top-down perceptual modulation are implicated in the pathophysiology of these phenomena. In healthy individuals, visual illusions are elicited by illusory figures through parametric manipulations of geometrical configurations, contrast, color, or spatial relationships between stimuli. These illusory percepts provide insight on the physiologic processes subserving conscious and unconscious perception. In this exploratory, cross-sectional, controlled study, perceptual performance on illusory figures was assessed on 11 PD patients with hallucinations, 10 non-hallucinating PD patients, and 10 age-matched healthy individuals. In order to characterize potential neural substrates of perceptual performances, patients' brain metabolic patterns on FDG PET were also analyzed. Illusions relying on attentional modulation and global perception were attenuated in PD patients without hallucinations. This pattern was no longer recognizable in hallucinating patients. Conversely, illusory effects normally counteracted by figure to background segregation and overlapping figures recognition were enhanced in PD patients with hallucinations. FDG PET findings further suggest that perceptual differences between PD patients might be linked to abnormal top-down perceptual modulation.

Abstract 15317: An Unusual Case of Recurrent Chest Pain: Lymphocytic Myocarditis

Case Presentation: A 42-year-old male with a past medical history of recurrent myopericarditis treated with a combination of NSAIDs, colchicine, and steroids presented for left-sided chest pain. The pain first recurred when he attempted a prednisone taper and he was started on Anakinra. Upon presentation, physical examination and laboratory findings were within normal limits. Echocardiography and electrocardiogram were within normal limits. Cardiac magnetic resonance imaging (CMR) showed transmural enhancement of the basal-mid inferolateral segments and patchy mid-myocardial enhancement in the basal-mid anterolateral segments. Nuclear medicine PET showed FDG uptake in the basal anteroseptal, anterolateral, inferolateral, inferior, and apical segments suggestive of active inflammation. Initially, the diagnosis was thought to be recurrent myopericarditis of unknown etiology. Subsequent right heart catheterization with endomyocardial biopsy (EMB) showed mononuclear infiltrates in the interstitium associated with myocyte infiltration and focal moderate interstitial fibrosis. Due to his clinical, imaging, and pathologic findings, he was diagnosed with lymphocytic myocarditis. His anti-inflammatory therapy regimen was reinstated, and he was started on Mycophenolate Mofetil. On follow-up, the patient had significant symptomatic improvement. Discussion: Lymphocytic myocarditis is a pattern of myocardial inflammation that is typically associated with autoimmune and idiopathic causes. Myocarditis frequently manifests with signs and symptoms of heart failure, including chest pain, dyspnea, and arrhythmias. Diagnosis of myocarditis is often supported by CMR and FDG-PET findings, however, EMB is the gold standard for the diagnosis of myocarditis. Treatment is generally supportive, though immunomodulatory therapies have gained increased popularity due to benefits in treating symptoms and preventing complications of heart failure.

Foreign body-type giant cell reaction with extensive granulation tissue and intense inflammation after chemotherapy mimicking residual lymphoma on FDG PET

Foreign body-type giant cell reaction is typically a biological and immunological reaction to the presence of foreign bodies such as catheters, parasites or biomaterials with a collection of fused macrophages (giant cell). We reported an unusual case of [18F]FDG PET findings in diffuse large B cell lymphoma in the urinary bladder following incomplete resection and chemotherapy. As the restaging [18F]FDG PET showed intense [18F]FDG uptake in the urinary bladder at the resection site concerning for recurrence, the lesion was subsequently resected and histopathology showed extensive granulation tissue with foreign body-type giant cell reaction with no suspected foreign bodies or neoplasia.

Impact of FDG PET/CT Scan in Changing Management of Well-Differentiated Neuroendocrine Tumors With Ki67 Index Less Than or Equal to 5.

This study aimed to see the impact of FDG PET/CT with somatostatin receptor PET (SSTR PET) in directing the treatment plan in lower-grade well-differentiated neuroendocrine tumors (NETs) with Ki67 index ≤5%. Sixty-three NET cases with Ki67 index ≤5% with both FDG PET and SSTR PET ( 68 Ga-DOTANOC PET) were included for this retrospective observational study. FDG PET findings were classified into positive, weakly positive, and negative based on a visual scale. Clinical factors considered while referring for FDG PET scan were audited from electronic medical records. The addition of chemotherapy was considered as FDG-directed change in treatment. Sixty patients showed intense SSTR expression in the primary and metastatic sites (if present). Three patients showed no evidence of SSTR expression, in whom the scans were done after resection of the primary tumor. The FDG PET was positive in 25 (39.6%), weakly positive in 11 (17.4%), and negative in 27 (42.8%). Specific clinical reason for doing FDG PET was found in 34 patients, and in the remaining 29, there was no justification or specific indication for doing the FDG study; 73.5% of patients from the former group was either FDG positive or weakly positive, and 26.5% were negative; in the other group, 62.1% were FDG-negative, and 37.9% were positive ( P = 0.004). Treatment-naive patients with symptom duration of ≤5 months were associated with more FDG positivity than patients with >5 months' symptom duration ( P = 0.006). FDG PET/CT led to change in management in 17.4% of all the patients, 9.6% of grade 1, and 25% of grade 2 patients. In lower-grade NET, FDG positivity was seen in a sizable number of the cases, and this led to change in management in 17.4% of the cases. Specific clinical features could be utilized to successfully discriminate between FDG-avid and non-FDG-avid disease in lower-grade NETs, and this had impact in management change as well.

Preclinical evaluation of [18F]FDG-PET as a biomarker of lymphoid tissue disease and inflammation in Zika virus infection

PurposeZika (ZIKV) is a viral inflammatory disease affecting adults, children, and developing fetuses. It is endemic to tropical and sub-tropical countries, resulting in half the global population at risk of infection. Despite this, there are no approved therapies or vaccines against ZIKV disease. Non-invasive imaging biomarkers are potentially valuable tools for studying viral pathogenesis, prognosticating host response to disease, and evaluating in vivo efficacy of experimental therapeutic interventions. In this study, we evaluated [18F]fluorodeoxyglucose ([18F]FDG)-positron emission tomography (PET) as an imaging biomarker of ZIKV disease in a mouse model and correlated metabolic tracer tissue uptake with real-time biochemical, virological, and inflammatory features of tissue infection.Methods[18F]FDG-PET/CT imaging was performed in an acute, lethal ZIKV mouse infection model, at increasing stages of disease severity. [18F]FDG-PET findings were corroborated with ex vivo wholemount-tissue autoradiography and tracer biodistribution studies. Tracer uptake was also correlated with in situ tissue disease status, including viral burden and inflammatory response. Immune profiling of the spleen by flow cytometry was performed to identify the immune cell subsets driving tissue pathology and enhancing tracer uptake in ZIKV disease.ResultsFoci of increased [18F]FDG uptake were consistently detected in lymphoid tissues—particularly the spleen—of ZIKV-infected animals. Splenic uptake increased with disease severity, and corroborated findings in tissue pathology. Increased splenic uptake also correlated with increased viral replication and elevated expression of pro-inflammatory cytokines within these tissues. ZIKV-infected spleens were characterized by increased infiltration of myeloid cells, as well as increased proliferation of both myeloid and lymphoid cells. The increased cell proliferation correlated with increased tracer uptake in the spleen. Our findings support the use of [18F]FDG as an imaging biomarker to detect and track ZIKV disease in real time and highlight the dependency of affected tissue on the nature of the viral infection.Conclusion[18F]FDG uptake in the spleen is a useful surrogate for interrogating in situ tissue viral burden and inflammation status in this ZIKV murine model.

Low EEG Gamma Entropy and Glucose Hypometabolism After Corpus Callosotomy Predicts Seizure Outcome After Subsequent Surgery.

BackgroundPatients with generalized epilepsy who had lateralized EEG abnormalities after corpus callosotomy (CC) occasionally undergo subsequent surgeries to control intractable epilepsy.ObjectivesThis study evaluated retrospectively the combination of EEG multiscale entropy (MSE) and FDG-PET for identifying lateralization of the epileptogenic zone after CC.MethodsThis study included 14 patients with pharmacoresistant epilepsy who underwent curative epilepsy surgery after CC. Interictal scalp EEG and FDG-PET obtained after CC were investigated to determine (1) whether the MSE calculated from the EEG and FDG-PET findings was lateralized to the surgical side, and (2) whether the lateralization was associated with seizure outcomes.ResultsSeizure reduction rate was higher in patients with lateralized findings to the surgical side than those without (MSE: p < 0.05, FDG-PET: p < 0.05, both: p < 0.01). Seizure free rate was higher in patients with lateralized findings in both MSE and FDG-PET than in those without (p < 0.05).ConclusionsThis study demonstrated that patients with lateralization of MSE and FDG-PET to the surgical side had better seizure outcomes. The combination of MSE and conventional FDG-PET may help to select surgical candidates for additional surgery after CC with good postoperative seizure outcomes.

Efficacy of myocardial washout of 99mTc-MIBI/Tetrofosmin for the evaluation of inflammation in patients with cardiac sarcoidosis: comparison with 18F-fluorodeoxyglucose positron emission tomography findings.

Both myocardial perfusion scintigraphy and 18F-fluorodeoxyglucose positron emission tomography (FDG PET) are useful for the diagnosis of cardiac sarcoidosis (CS). However, the association between the washout of 99mTc-labeled tracer and FDG PET has not been established. This study aimed to evaluate the association between the washout of 99mTc-labeled tracer and FDG PET findings in patients with CS. We retrospectively analyzed 64 patients (65.0 ± 11.2years, 53% male) with suspected CS who underwent myocardial single-photon emission computed tomography (SPECT) with 99mTc-labeled tracer and FDG PET. The SPECT images were acquired at 15min (early images) and 3h (delayed images) after injection and scored visually using a 17-segment model with a 5-point scoring system. The washout score was defined as the difference between the early and delayed total defect scores. FDG positivity was considered as focal or focal on diffuse patterns on visual assessment, and FDG uptake was quantified by measuring the standardized uptake value (SUV) of each of the 17 segments. The washout score was significantly higher for the CS group than for the non-CS group (3.0 [-1.0-5.0] vs. 0.0 [-0.5-1.0], p = 0.010). Receiver operating characteristic analysis showed that a washout score of ≥ 2 had the best accuracy for detecting CS (88% sensitivity and 56% specificity) and FDG positivity (71% sensitivity and 89% specificity). In the segment-based analysis of 833 segments from 49 patients, excluding 15 patients with diffuse FDG uptake, the median SUVs for FDG uptake for the washout scores of ≤ 0, 1, and 2 were 2.3 (1.8-3.6), 4.2 (2.9-7.8), and 8.3 (6.5-9.4), respectively (p < 0.001). The washout of 99mTc-labeled tracer can be a useful marker for the evaluation of FDG PET findings in patients with CS.

Assessing the correlation between FDG PET findings of IDC breast carcinoma and histopathology of coexisting ductal carcinoma in-situ.

Ductal carcinoma in-situ (DCIS) often coexists with invasive ductal carcinoma (IDC) of the breast. DCIS is considered as a non-obligate precursor of IDC when both coexist. 18F-fluorodeoxyglucose positron emission tomography/computed tomography ([18F]FDG PET/CT) imaging is commonly used in the staging and follow-up assessment of breast cancer. In this study, we aimed to assess if there is any correlation between primary tumor PET and histopathology findings and histopathological features of the coexisting DCIS. FDG PET/CT images and histopathology results of the patients with newly diagnosed breast cancer (IDC) with coexisting DCIS were analyzed in this retrospective study. The grade and size of the primary tumor and histopathological features of the coexisting DCIS (nuclear grade and architectural pattern) were obtained from the postoperative histopathology results. Maximum standardized uptake values (SUV: SUVmax and SULmax) of the primary tumor normalized by weight and lean body mass were measured. Statistical analysis was performed to assess the correlation between various parameters of IDC and DCIS. This study included sixty-two (62) patients with IDC-DCIS. Primary tumor grade was significantly correlated and associated with the nuclear grade of the coexisting DCIS (polychoric correlation r = 0.736, and Fisher exact test, PV < 0.001, respectively). Primary tumor SUV was not correlated with the nuclear grade and architectural pattern of the coexisting DCIS (polyserial correlation r = 0.172, PV = 0.155, and Point Bi-Serial correlation r = -0.009, PV = 0.955, respectively). Median primary tumor size was marginally significantly different among DCIS nuclear grades but it was not significantly different in comedo and non-comedo cases (Kruskal-Wallis test PV = 0.053, and Mann-Whitney U test PV = 0.890, respectively). Primary tumor grade is correlated with the nuclear grade of the coexisting DCIS. SUV of primary tumor does not seem to be correlated with the histopathological features of coexisting DCIS (nuclear grade and architectural pattern) but this may be further studied in a larger number of patients.

Use of 18F-fluorodeoxyglucose positron emission tomography to standardize clinical trial recruitment in Takayasu's arteritis.

To assess whether data from 18F-fluorodeoxyglucose (FDG) PET should be incorporated into eligibility criteria for clinical trials in Takayasu's arteritis (TAK). The study was conducted in two parts. Part one was an international online survey among physicians with experience managing TAK to determine, using clinical vignettes, whether FDG-PET data influence decisions about enrolment in trials. Part two used patient data from an observational cohort study in TAK to assess agreement regarding decisions about enrolment into trials, based on clinical assessment with and without incorporation of FDG-PET data. In part one, 68 physicians responded to the survey. Most physicians had used FDG-PET to diagnose TAK (82%) or monitor disease activity (66%). In vignettes representing active clinical disease, FDG-PET findings increased physician confidence in disease assessment and reduced outlier assessments. The greatest variability in decisions regarding enrolment into trials was observed in vignettes representing constitutional symptoms alone and elevated acute-phase reactants. In these cases, FDG-PET findings influenced decisions about enrolment and improved physician confidence. In multivariable models, FDG-PET findings were 1.29 times more strongly associated with enrolment decisions compared with levels of acute-phase reactants. In part two, incorporation of FDG-PET data significantly improved agreement about enrolment decisions between raters [inter-rater reliability (IRR) = 0.68 (95% CI 0.67, 0.69) to IRR = 0.88 (95% CI 0.87, 0.89); P < 0.01]. Incorporation of FDG-PET data into assessment of TAK influences decisions about enrolment of patients into trials, improves physician confidence about clinical assessment and could help reduce variability in study populations. Future trials in TAK should consider incorporating FDG-PET data into eligibility criteria.

FDG-PET findings and alcohol-responsive myoclonus in a patient with Unverricht-Lundborg disease.

The aim of this report is to describe clinical, EEG, and neuroimaging findings in a patient with Unverricht-Lundborg disease (ULD), the most common form of progressive myoclonus epilepsy (PME). A 23-year-old male with genetically confirmed ULD had a phenotype consisting of myoclonus, generalized seizures, intellectual disability, ataxia, and dysarthria. Myoclonus and gait disturbance were strongly ameliorated by alcohol consumption. EEG revealed a posterior dominant rhythm with alpha variant, mild bilateral slowing, and anterior-predominant epileptiform abnormalities. Brain MRI showed mild cerebellar atrophy. FDG-PET revealed hypometabolism more prominent in the posterior brainstem, thalami, frontal and parietal lobes. This report confirms that alcohol may ameliorate myoclonus in a subset of patients with PME, including genetically confirmed ULD. In addition, the presence of FDG-PET hypometabolism predominant in the frontoparietal region and thalami has not been previously described in ULD, yet is consistent with previous brain morphometry studies showing motor cortex and thalamic atrophy in ULD, and brings into question the possibility of a shared metabolic pattern with other PMEs, notably Lafora disease.