EANM consensus document on the use of [18F]FDG PET/CT in fever and inflammation of unknown origin.

PURPOSE: Patients with fever and inflammation of unknown origin (FUO/IUO) are clinically challenging due to variable clinical presentations with nonspecific symptoms and many differential diagnoses. Positron emission tomography/computed tomography (PET/CT) with 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) is increasingly used in FUO and IUO, but the optimal diagnostic strategy remains controversial. This consensus document aims to assist clinicians and nuclear medicine specialists in the appropriate use of [18F]FDG-PET/CT in FUO and IUO based on current evidence. METHODS: A working group created by the EANM infection and inflammation committee performed a systematic literature search based on PICOs with "patients with FUO/IUO" as population, "[18F]FDG-PET/CT" as intervention, and several outcomes including pre-scan characteristics, scan protocol, diagnostic yield, impact on management, prognosis, and cost-effectiveness. RESULTS: We included 68 articles published from 2001 to 2023: 9 systematic reviews, 49 original papers on general adult populations, and 10 original papers on specific populations. All papers were analysed and included in the evidence-based recommendations. CONCLUSION: FUO and IUO remains a clinical challenge and [18F]FDG PET/CT has a definite role in the diagnostic pathway with an overall diagnostic yield or helpfulness in 50-60% of patients. A positive scan is often contributory by directly guiding treatment or subsequent diagnostic procedure. However, a negative scan may be equally important by excluding focal disease and predicting a favorable prognosis. Similar results are obtained in specific populations such as ICU-patients, children and HIV-patients.

Dapagliflozin treatment is associated with a reduction of epicardial adipose tissue thickness and epicardial glucose uptake in human type 2 diabetes.

OBJECTIVE: We recently demonstrated that treatment with sodium-glucose cotransporter-2 inhibitors (SGLT-2i) leads to an increase in myocardial flow reserve in patients with type 2 diabetes (T2D) with stable coronary artery disease (CAD). The mechanism by which this occurs is, however, unclear. One of the risk factors for cardiovascular disease is inflammation of epicardial adipose tissue (EAT). Since the latter is often increased in type 2 diabetes patients, it could play a role in coronary microvascular dysfunction. It is also well known that SGLT-2i modify adipose tissue metabolism. We aimed to investigate the effects of the SGLT-2i dapagliflozin on metabolism and visceral and subcutaneous adipose tissue thickness in T2D patients with stable coronary artery disease and to verify whether these changes could explain observed changes in myocardial flow. METHODS: We performed a single-center, prospective, randomized, double-blind, controlled clinical trial with 14 T2D patients randomized 1:1 to SGLT-2i dapagliflozin (10 mg daily) or placebo. The thickness of visceral (epicardial, mediastinal, perirenal) and subcutaneous adipose tissue and glucose uptake were assessed at baseline and 4 weeks after treatment initiation by 2-deoxy-2-[18F]fluoro-D-glucose Positron Emission Tomography/Computed Tomography during hyperinsulinemic euglycemic clamp. RESULTS: The two groups were well-matched for baseline characteristics (age, diabetes duration, HbA1c, BMI, renal and heart function). Dapagliflozin treatment significantly reduced EAT thickness by 19% (p = 0.03). There was a significant 21.6% reduction in EAT glucose uptake during euglycemic hyperinsulinemic clamp in the dapagliflozin group compared with the placebo group (p = 0.014). There were no significant effects on adipose tissue thickness/metabolism in the other depots explored. CONCLUSIONS: SGLT-2 inhibition selectively reduces EAT thickness and EAT glucose uptake in T2D patients, suggesting a reduction of EAT inflammation. This could explain the observed increase in myocardial flow reserve, providing new insights into SGLT-2i cardiovascular benefits.

Dapagliflozin improves myocardial flow reserve in patients with type 2 diabetes: the DAPAHEART Trial: a preliminary report.

OBJECTIVE: Cardiovascular (CV) outcome trials have shown that in patients with type 2 diabetes (T2D), treatment with sodium-glucose cotransporter-2 inhibitors (SGLT-2i) reduces CV mortality and hospital admission rates for heart failure (HF). However, the mechanisms behind these benefits are not fully understood. This study was performed to investigate the effects of the SGLT-2i dapagliflozin on myocardial perfusion and glucose metabolism in patients with T2D and stable coronary artery disease (coronary stenosis ≥ 30% and < 80%), with or without previous percutaneous coronary intervention (> 6 months) but no HF. METHODS: This was a single-center, prospective, randomized, double-blind, controlled clinical trial including 16 patients with T2D randomized to SGLT-2i dapagliflozin (10 mg daily) or placebo. The primary outcome was to detect changes in myocardial glucose uptake (MGU) from baseline to 4 weeks after treatment initiation by [(18)F]2-deoxy-2-fluoro-D-glucose (FDG) PET/CT during hyperinsulinemic euglycemic clamp. The main secondary outcome was to assess whether the hypothetical changes in MGU were associated with changes in myocardial blood flow (MBF) and myocardial flow reserve (MFR) measured by 13N-ammonia PET/CT. The study was registered at eudract.ema.europa.eu (EudraCT No. 2016-003614-27) and ClinicalTrials.gov (NCT03313752). RESULTS: 16 patients were randomized to dapagliflozin (n = 8) or placebo (n = 8). The groups were well-matched for baseline characteristics (age, diabetes duration, HbA1c, renal and heart function). There was no significant change in MGU during euglycemic hyperinsulinemic clamp in the dapagliflozin group (2.22 ± 0.59 vs 1.92 ± 0.42 µmol/100 g/min, p = 0.41) compared with the placebo group (2.00 ± 0.55 vs 1.60 ± 0.45 µmol/100 g/min, p = 0.5). Dapagliflozin significantly improved MFR (2.56 ± 0.26 vs 3.59 ± 0.35 p = 0.006 compared with the placebo group 2.34 ± 0.21 vs 2.38 ± 0.24 p = 0.81; pint = 0.001) associated with a reduction in resting MBF corrected for cardiac workload (p = 0.005; pint = 0.045). A trend toward an increase in stress MBF was also detected (p = 0.054). CONCLUSIONS: SGLT-2 inhibition increases MFR in T2D patients. We provide new insight into SGLT-2i CV benefits, as our data show that patients on SGLT-2i are more resistant to the detrimental effects of obstructive coronary atherosclerosis due to increased MFR, probably caused by an improvement in coronary microvascular dysfunction. Trial registration EudraCT No. 2016-003614-27; ClinicalTrials.gov Identifier: NCT03313752.

The impact of the COVID-19 pandemic on oncological disease extent at FDG PET/CT staging: the ONCOVIPET study.

PURPOSE: To investigate whether the COVID-19 pandemic and national lockdown had an impact on the extent of cancer disease at FDG PET/CT staging as surrogate marker. METHODS: Retrospective observational study including cancer patients submitted to FDG PET/CT staging from June 1 to October 31, 2020, and June 1 to October 31, 2019, respectively. Data regarding primary tumour, nodal (N) status and number of involved nodal stations, and presence and number of distant metastases (M) were collected. Each scan was classified in limited vs advanced status. Data were aggregated across the study population and tumour type. Bi-weekly frequencies of the observed events were analysed. RESULTS: Six hundred eleven patients were included (240 in 2019 vs 371 in 2020, respectively). A significant increase of advanced disease patients (rate 1.56, P < 0.001), N + or M + patients (rate 1.84 and 2.09, respectively, P < 0.001), and patients with a greater number of involved N stations or M (rate 2.01 and 2.06, respectively, P < 0.001) were found in 2020 compared with data of 2019. Analysis by tumour type showed a significant increase of advanced disease in lymphoma and lung cancer in 2020 compared with 2019 (P < 0.001). In addition, a significant increase of nodal involvement was found in lung, gastro-intestinal, and breast cancers, as well as in lymphoma patients (P < 0.02). A significant increase of distant metastases was found in lung cancers (P = 0.002). CONCLUSION: Cancer patients with advanced disease at FDG PET/CT staging increased in 2020 compared with 2019, following the national lockdown due to the COVID-19 pandemic, 1.5-fold with a significant increase of patients with N or M involvement. Targeted health interventions are needed to mitigate the effects of the pandemic on patient outcome.

The role of PET/CT in connective tissue disorders: systemic sclerosis, Sjögren's syndrome and systemic lupus erythematosus.

Advanced imaging techniques are needed to help clinicians in the diagnosis, in the choice of the right time for therapeutic interventions or for modifications and monitoring of treatment response in patients with autoimmune connective tissue diseases. Nuclear medicine imaging, especially PET/CT and PET/MRI, may play an important role in detecting disease activity, assessing early treatment response as well as in clarifying the complex mechanisms underlying systemic sclerosis, Sjögren's syndrome or systemic lupus erythematosus. In addition, [18F]FDG PET/CT may help in excluding or detecting coexisting malignancies. Other more specific radiopharmaceuticals are being developed and investigated, targeting specific cells and molecules involved in connective tissue diseases. Further larger studies with standardized imaging protocol and image interpretation are strongly required before including PET/CT in the diagnostic work-up of subsets of patients with autoimmune connective tissue diseases.

Are the simplified methods to estimate Ki in 18F-FDG PET studies feasible in clinical routine? Comparison between three simplified methods.

BACKGROUND: The aim of this study was to verify the feasibility, in clinical practice, of three simplified methods (Hunter, Sadato and another one proposed by our group) to calculate Ki and MRglu of 18F-FDG, comparing the results with those derived by the linear regression (LR) method (considered the golden standard), and also with SUV. METHODS: Forty-five patients (32males, mean age 69±9years) with non-small-cell-lung cancer prospectively enrolled, underwent dynamic 18F-FDG PET-CT over the thorax. Ki was estimated as follows: from a static acquisition and performing one venous blood sampling using the Hunter method; multiplying the SUV for the average plasma clearance rate (kP(T)) and for the initial distribution volume (V0bw) without performing any blood sampling using the Sadato method; multiplying the SUV for a factor F (which encompasses the mean value of haematocrit and plasma volume, both according to patient's sex) without performing any blood sample using ours method. Wilcoxon signed rank and coefficient of determination (R2) were used for statistical analysis. RESULTS: No significant difference was observed between the Ki and MRglu estimated by all three simplified methods and the Ki and MRglu estimated by LR. The highest P values and the lower values of mean differences were observed with our method compared with LR: Ki=0.0392±0.0178 min-1 vs. Ki=0.0392±0.0202 min-1 (P=0.897, MD=0.0001 min-1), respectively; MRglu= 4.47±2.23 ml/min/100g vs. MRglu= 4.43±2.38 ml/min/100g (P=0.839, MD= -0.0373 mL/min/100g), respectively. The highest correlation was observed between the Ki estimated by both Hunter and our methods and the Ki estimated by LR: R2=0.87, R2=0.86, respectively. A good correlation (R2=0.83) was observed between SUV and Ki estimated by LR. CONCLUSIONS: These three simplified methods represent a valid alternative to the more invasive and complex full kinetic analysis. Their "pros" are: the non-invasiveness, the feasibility, the good correlation with the golden standard; their "cons" is that full kinetic analysis provides highest accuracy in Ki determination. Therefore, in clinical oncology routine, the nuclear physicians can choose among different simplified methods especially for monitoring the response to treatment, for tumour grading, and for prognostic stratification, letting the full kinetic analysis to specific centre/studies.

Clinical relevance of PET myocardial blood flow quantification.

Until a few years ago, myocardial perfusion imaging (MPI) using positron-emission tomography (PET) and the absolute quantification of myocardial blood flow (MBF) was limited to research institutions. Following an increase in the number of PET scanner installations and in the availability of perfusion tracers that do not have to be produced by an on-site cyclotron and commercial software for MBF quantification, a more widespread clinical use of MBF quantification with PET can be expected. This article aims to provide a comprehensive overview of the advantages of MBF quantification with PET highlighting the potential applications in several clinical settings, from patients with cardiovascular risk factors and early coronary artery disease (CAD) to patients with multi-vessel or myocardial disease. Finally, using current evidence, the independent and incremental prognostic information of MBF quantification with PET in addition to the visual interpretation of MPI will also be described.

The predictive value of 18F-FDG PET/CT for assessing pathological response and survival in locally advanced rectal cancer after neoadjuvant radiochemotherapy.

PURPOSE: To evaluate whether metabolic changes in the primary tumour during and after preoperative radiochemotherapy (RCT) can predict the histopathological response in patients with locally advanced rectal cancer as well as disease-free survival (DFS) and overall survival (OS). METHODS: Consecutive patients with cT2-4 N0-2 rectal adenocarcinoma were included. (18)F-FDG PET/CT was performed at baseline, at the end of the second week of RCT (early PET/CT) and before surgery (late PET/CT). The PET/CT results were compared with histopathological data (ypT0 N0 vs. ypT1-4 N0-2 as well as TRG1 vs.TRG2-5) and survival. RESULTS: The study included 126 patients. Among 124 patients in whom TNM classification was available, 28 (22.6 %) were ypT0 N0, and among all 126 patients, 31 (24.6 %) were TRG1. The areas under the curve of the early response index (RI) for identifying non-complete pathological response (non-cPR) were 0.74 (95 % CI 0.61 - 0.87) for ypT1-4 N0-2 patients and 0.75 (95 % CI 0.62 - 0.88) for TRG2-5 patients. The optimal cut-off for differentiating patients with non-cPR and cPR was found to be a reduction of 61.2 % (83.1 % sensitivity and 65 % specificity in ypT1-4 N0-2 patients; 85.4 % sensitivity and 65.2 % specificity in TRG2-5 patients). The optimal cut-off for late RI could not be found. The qualitative analysis of images obtained after RCT demonstrated 81.5 % sensitivity and 61.3 % specificity in predicting TRG2-5. After a median follow-up of 68 months, the low number of patients with local/distant recurrence or who had died did not allow the value of PET/CT for predicting DFS and OS to be calculated. CONCLUSION: The early assessment of response to RCT by (18)F-FDG PET/CT can predict non-cPR allowing practical modification of preoperative treatment. Conversely, late RI is not sufficiently accurate for guiding the decision as to whether local excision or even observation is appropriate in an individual patient. Qualitative analysis of late PET/CT images is also not sensitive enough alone to rule out the presence of residual disease.

Cardiovascular implantable electronic device infection: delayed vs standard FDG PET-CT imaging.

BACKGROUND: Positron emission tomography-computed tomography (PET-CT) with (18)F-fluorodeoxyglucose (FDG) has emerged as a rapidly evolving diagnostic tool for infectious diseases. However, the optimal imaging time in this clinical setting is not clear yet. The aim of this study is to investigate whether delayed (3 hours) FDG PET-CT could increase the diagnostic accuracy of this technique compared to standard (1 hour) imaging in the detection of septic foci involving the pocket and/or pacing leads in patients with suspected cardiovascular implantable electronic device (CIED) infection scheduled for device removal. METHODS AND RESULTS: Twenty-seven patients underwent standard and delayed imaging. PET-CT results were compared to bacteriological cultures after CIED removal. Fifteen controls free of infection underwent PET-CT imaging as part of investigation of malignancy. The diagnostic accuracy of delayed imaging was significantly higher than 1-hour scan for lead infection (70% vs 51%, P = .024). No significant difference was found between standard and delayed diagnostic accuracy for pocket or device infection. Semi-quantitative analysis showed that mean pocket and lead target-to-background ratio were significantly higher on delayed compared to standard imaging (3.7 ± 1.9 vs 1.6 ± 1.1, P = .0002; 3.0 ± 1.3 vs 0.7 ± 1.0, P = .01). CONCLUSIONS: Delayed FDG PET-CT imaging should be considered at least in patients with negative 1-hour scan and founded suspicion of pacing lead infection.

Atypical Presentation of Splenic Tissue Mimicking Neuroendocrine Tumor Relapse.

ABSTRACT: A 61-year-old man underwent splenopancreasectomy for a 3-cm neuroendocrine tumor of the body of the pancreas (G2, pT1 pN0, Ki67 3%). Five months after surgery 68Ga-DOTATOC PET/CT showed increased radiotracer uptake in a solid tissue of the splenic fossa, possibly referring to a splenosis nodule. After 19 months, a further 68Ga-DOTATOC PET/CT showed a significant functional and dimensional increase of the previously detected tissue and the appearance of a new finding in the left lateral abdominal wall. In the suspicion of neuroendocrine tumor relapse, the patient underwent surgical excision of the documented lesions. Histology showed splenosis in both nodules.

Breast Relapse of Pediatric B-Cell Acute Lymphoblastic Leukemia After CAR-T Therapy Detected by 18F-FDG PET/CT.

BACKGROUND: B-cell acute lymphoblastic leukemia (B-ALL) is the most common childhood malignancy. Medullary and extramedullary disease relapse is a well-known occurrence in B-ALL pediatric patients treated with standard chemo-immunotherapy and, more recently, with chimeric antigen receptor (CAR)-T cell therapy. 18F-Fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) emerges as a sensitive imaging tool for detecting disease relapse at extra-medullary sites, with only limited literature evidence in the CAR-T therapy setting. CASE REPORT: In a 12-year-old female treated with CAR-T therapy for B-ALL relapse, 18F-FDG PET/CT scan performed for surveillance, after disease remission, detected a solitary and clinically occult relapse in the breast parenchyma that was histologically confirmed. CONCLUSION: At our knowledge, this is the first report about a pediatric B-ALL patient with a solitary and occult breast relapse after CAR-T therapy, early discovered by 18F-FDG PET/CT during disease monitoring.

Role of 18F-FDG PET/CT in Head and Neck Squamous Cell Carcinoma: Current Evidence and Innovative Applications.

This article provides an overview of the use of 18F-FDG PET/CT in various clinical scenarios of head-neck squamous cell carcinoma, ranging from initial staging to treatment-response assessment, and post-therapy follow-up, with a focus on the current evidence, debated issues, and innovative applications. Methodological aspects and the most frequent pitfalls in head-neck imaging interpretation are described. In the initial work-up, 18F-FDG PET/CT is recommended in patients with metastatic cervical lymphadenectomy and occult primary tumor; moreover, it is a well-established imaging tool for detecting cervical nodal involvement, distant metastases, and synchronous primary tumors. Various 18F-FDG pre-treatment parameters show prognostic value in terms of disease progression and overall survival. In this scenario, an emerging role is played by radiomics and machine learning. For radiation-treatment planning, 18F-FDG PET/CT provides an accurate delineation of target volumes and treatment adaptation. Due to its high negative predictive value, 18F-FDG PET/CT, performed at least 12 weeks after the completion of chemoradiotherapy, can prevent unnecessary neck dissections. In addition to radiomics and machine learning, emerging applications include PET/MRI, which combines the high soft-tissue contrast of MRI with the metabolic information of PET, and the use of PET radiopharmaceuticals other than 18F-FDG, which can answer specific clinical needs.

Dapagliflozin-Induced Myocardial Flow Reserve Improvement is not Associated with HDL Ability to Stimulate Endothelial Nitric Oxide Production.

BACKGROUND: Sodium-glucose cotransporter-2 (SGLT2) inhibitors have shown controversial results in modulating plasma lipids in clinical trials. Most studies found slight increases in high-density lipoprotein (HDL) cholesterol but few have provided evidence on HDL functionality with disappointing results. However, there is broad agreement that these drugs provide cardiovascular protection through several mechanisms. Our group demonstrated that dapagliflozin improves myocardial flow reserve (MFR) in patients with type 2 diabetes (T2D) with coronary artery disease (CAD). The underlying mechanisms are still unknown, although in vitro studies have suggested the involvement of nitric oxide (NO). AIM: To investigate changes in HDL-mediated modulation of NO production with dapagliflozin and whether there is an association with MFR. METHODS: Sixteen patients with CAD-T2D were enrolled and randomized 1:1 to dapagliflozin or placebo for 4 weeks. Blood samples were collected before and after treatment for each group. The ability of HDL to stimulate NO production in endothelial cells was tested in vitro by incubating human umbilical vein endothelial cells (HUVEC) with apoB-depleted (apoB-D) serum of these patients. The production of NO was assessed by fluorescent assay, and results were expressed as fold versus untreated cells. RESULTS: Change in HDL-mediated NO production remained similar in dapagliflozin and placebo group, even after adjustment for confounders. There were no significant correlations between HDL-mediated NO production and MFR either at baseline or after treatment. No changes were found in HDL cholesterol in either group, while low-density lipoprotein cholesterol (LDL cholesterol) significantly decreased compared to baseline only in treatment group (p = 0.043). CONCLUSIONS: In patients with T2D-CAD, beneficial effects of dapagliflozin on coronary microcirculation seem to be unrelated to HDL functions. However, HDL capacity to stimulate NO production is not impaired at baseline; thus, the effect of drug treatments would be negligible. To conclude, we can assume that HDL-independent molecular pathways are involved in the improvement of MFR in this population. TRIAL REGISTRATION: EudraCT No. 2016-003614-27; ClinicalTrials.gov Identifier: NCT03313752.

The Role of Fibroblast Activation Protein Inhibitor Positron Emission Tomography in Inflammatory and Infectious Diseases: An Updated Systematic Review.

The role of fibroblast activation protein inhibitor (FAPI) positron emission tomography/computed tomography (PET/CT) is emerging for the assessment of non-oncological diseases, such as inflammatory and infectious diseases, even if the evidence in the literature is still in its initial phases. We conducted a systematic search of Scopus, PubMed/MEDLINE, Embase, and Cochrane library databases for studies published before 31 December 2023 reporting infectious and inflammatory disease imaging with FAPI PET/CT. We included twenty-one studies for a total of 1046 patients. The most frequent disease studied was lung interstitial disease, investigated in six studies for a total of 200 patients, followed by bone and joint diseases in two studies and 185 patients, IgG4-related disease in 53 patients, and Crohn's disease in 30 patients. Despite the heterogeneity of studies in terms of study design and technical features, FAPI PET/CT showed a high detection rate and diagnostic role. Moreover, when compared with 2-[18F]FDG PET/CT (n = 7 studies), FAPI PET/CT seems to have better diagnostic performances. The presence of chronic inflammation and tissue remodeling, typical of immune-mediated inflammatory conditions, may be the underlying mechanism of FAPI uptake.

Predicting time to treatment in follicular lymphoma on watchful waiting using baseline metabolic tumour burden.

PURPOSE: Asymptomatic patients with follicular lymphoma (FL) and a low tumour burden can be followed without initial therapy, a strategy called watchful waiting (WW). Prediction of the time to treatment (TTT) is still a challenge. We investigated the prognostic value of baseline total metabolic tumour volume (TMTV) and whole-body total lesion glycolysis (WB-TLG) to predict TTT in patients with FL on WW. METHODS: We conducted a retrospective study of 54 patients with FL (grade 1-3a) diagnosed between June 2013 and December 2019, staged with FDG PET/CT, and managed on WW. Median age was 62 years (range 34-85), stage was advanced (III-IV) in 57%, and FLIPI score was intermediate to high (≥ 2) in 52% of the patients. RESULTS: The median TMTV and WB-TLG were 7.1 and 43.3, respectively. With a median follow-up of 59 months, 41% of patients started immuno-chemotherapy. The optimal cut-points to identify patients with TTT within 24 months were 14 for TMTV (AUC 0.70; 95% CI 51-88) and 64 for WB-TLG (AUC 0.71; 95% CI 52-89) (p < 0.005). The probability of not having started treatment within 24 months was 87% for TMTV < 14 and 53% for TMTV ≥ 14 (p < 0.005). TMTV was independent of the FLIPI score for TTT prediction. Patients with both FLIPI ≥ 2 and TMTV ≥ 14 had only an 18% probability of not having started treatment at 36 months, while this probability was 75% in patients with TMTV < 14. CONCLUSION: Metabolic tumour volume parameters may add information to clinical scores to better predict TTT and better stratify patients for interventional studies.

Early evaluation of cerebral metabolic rate of glucose (CMRglu) with 18F-FDG PET/CT and clinical assessment in idiopathic normal pressure hydrocephalus (INPH) patients before and after ventricular shunt placement: preliminary experience.

PURPOSE: We evaluated the relationships between the cerebral metabolic rate of glucose (CMRglu) measured by dynamic (18)F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) and the clinical and neuropsychological assessment before and after the surgical procedure in idiopathic normal pressure hydrocephalus (INPH) patients. METHODS: Eleven selected INPH patients underwent clinical assessment (modified Rankin scale, Krauss scale, Larsson categorization system and Stein-Langfitt scale), cognitive evaluation (Mini-Mental State Examination, MMSE) and dynamic (18)F-FDG PET/CT scan 3 days before and 1 week after ventricular shunt placement. RESULTS: After shunting, the global CMRglu significantly increased (2.95 ± 0.44 vs 4.38 ± 0.68, p = 10(-7)) in all INPH patients with a mean percentage value of 48.7%. After shunting, no significant change was found in the Evans ratio whereas a significant decrease in all clinical scale scores was observed. Only a slight reduction in the MMSE was found. After shunting, a significant correlation between the global CMRglu value and clinical assessment was found (R (2) = 0.75, p = 0.024); indeed all clinical scale scores varied (decreasing) and the CMRglu value also varied (increasing) in all INPH patients. CONCLUSION: Our preliminary data show that changes in the CMRglu are promptly reversible after surgery and that there is a relationship between the early metabolic changes and clinical symptoms, independently from the simultaneous changes in the ventricular size. The remarkable and prompt improvement in the global CMRglu and in symptoms may also have important implications for the current concept of "neuronal plasticity" and for the cells' reactivity in order to recover their metabolic function.

Integrated imaging of non-small cell lung cancer recurrence: CT and PET-CT findings, possible pitfalls and risk of recurrence criteria.

OBJECTIVES: To review the role of imaging in the diagnosis of recurrent disease in previously treated non-small cell lung cancer (NSCLC) and discuss the imaging pitfalls. METHODS: A comprehensive review of published literature on CT and PET imaging of NSCLC recurrence was performed. Diagnostic and prognostic values are discussed. Representative imaging examples are illustrated. RESULTS: Up to 30% of NSCLC recurrences present as loco-regional, involving treated hemithorax and ipsilateral lymph nodes, while 70% present as metachronous distant metastases. CT and PET-CT play an important role in the early detection of recurrence; indications for imaging vary depending on pathological features. CONCLUSION: Imaging plays a central role in the identification of recurrence and may predict prognosis. KEY POINTS: Lung cancer recurs after surgery in 30% to 75% of patients. CT and PET-CT are crucial in identification of loco-regional recurrence. Knowledge of potential pitfalls is essential, especially for parenchymal or nodal recurrence. CT can diagnose metastases but further examinations (PET-CT, MRI) are often needed. Morphological and functional imaging criteria may help in predicting recurrence.