Leon Menezes

Idiopathic Pulmonary Fibrosis and Diffuse Parenchymal Lung Disease: Implications from Initial Experience with 18F-FDG PET/CT

The purpose of this study was to evaluate integrated 18F-FDG PET/CT in patients with idiopathic pulmonary fibrosis (IPF) and diffuse parenchymal lung disease (DPLD). Methods: Thirty-six consecutive patients (31 men and 5 women; mean age ± SD, 68.7 ± 9.4 y) with IPF (n = 18) or other forms of DPLD (n = 18) were recruited for PET/CT and high-resolution CT (HRCT), acquired on the same instrument. The maximal pulmonary 18F-FDG metabolism was measured as a standardized uptake value (SUVmax). At this site, the predominant lung parenchyma HRCT pattern was defined for each patient: ground-glass or reticulation/honeycombing. Patients underwent a global health assessment and pulmonary function tests. Results: Raised pulmonary 18F-FDG metabolism in 36 of 36 patients was observed. The parenchymal pattern on HRCT at the site of maximal 18F-FDG metabolism was predominantly ground-glass (7/36), reticulation/honeycombing (26/36), and mixed (3/36). The mean SUVmax in patients with ground-glass and mixed patterns was 2.0 ± 0.4, and in reticulation/honeycombing it was 3.0 ± 1.0 (Mann–Whitney U test, P = 0.007). The mean SUVmax in patients with IPF was 2.9 ± 1.1, and in other DPLD it was 2.7 ± 0.9 (Mann–Whitney U test, P = 0.862). The mean mediastinal lymph node SUVmax (2.7 ± 1.3) correlated with pulmonary SUVmax (r = 0.63, P < 0.001). Pulmonary 18F-FDG uptake correlated with the global health score (r = 0.50, P = 0.004), forced vital capacity (r = 0.41, P = 0.014), and transfer factor (r = 0.37, P = 0.042). Conclusion: Increased pulmonary 18F-FDG metabolism in all patients with IPF and other forms of DPLD was observed. Pulmonary 18F-FDG uptake predicts measurements of health and lung physiology in these patients. 18F-FDG metabolism was higher when the site of maximal uptake corresponded to areas of reticulation/honeycomb on HRCT than to those with ground-glass patterns.

Increased Metabolic Activity in Abdominal Aortic Aneurysm Detected by 18F-Fluorodeoxyglucose (18F-FDG) Positron Emission Tomography/Computed Tomography (PET/CT)

OBJECTIVES Abdominal aortic aneurysms (AAAs) are associated with an inflammatory cell infiltrate and enzymatic degradation of the vessel wall. The aim of this study was to detect increased metabolic activity in the wall of the AAA with 18F-fluorodeoxyglucose ((18)F-FDG), mediated by glucose transporter protein (GLUTs), using a dedicated hybrid PET/64-detector CT. DESIGN, METHOD AND MATERIALS: 14 patients (All male, mean age 73.6 years, range 61-82) with AAA under surveillance underwent PET/CT scanning with 175 MBq of intravenous (18)F-FDG. The maximum aneurysm diameter and calcification score were determined on the attenuation correction CT. A volume of interest was placed on the aneurysm sac and the maximum Standardised Uptake Value (SUV(max)) measured. RESULTS The mean aneurysm diameter was 5.4 cm (SD+/-0.8). Two aneurysms had the CT characteristics of inflammatory aneurysms. Twelve aneurysms showed increased FDG uptake (SUV(max)>2.5). There was no significant difference in FDG uptake between heavily calcified aneurysms and non-heavily calcified aneurysms (t-test). There was a significant increase in the FDG uptake in the two inflammatory aneurysms compared to the other twelve aneurysms (t-test; P=0.04). CONCLUSION The findings in this study offer in vivo evidence that the AAA wall shows increased glucose metabolism, mediated by the GLUTs: this increased metabolic activity as detected by PET/CT may be present in most AAAs.

Vascular Inflammation Imaging with 18F-FDG PET/CT: When to Image?

We prospectively investigated the ideal imaging time to measure vascular uptake after injection of 18F-FDG. Methods: A total of 17 patients with atherosclerotic abdominal aortic aneurysm underwent dynamic abdominal PET/CT using 2-min frames between 45 and 53, 57 and 65, 115 and 123, and 175 and 183 min after injection of 18F-FDG. For each period of dynamic imaging, vessel wall and lumen uptake were measured using the maximum standardized uptake value (SUVmax) and target-to-background ratio (TBR). Results: No significant difference in TBR across all time points (repeated measures ANOVA, P = 0.206) was observed, despite a significant difference in aortic wall and lumen uptake with time (repeated measures ANOVA, P = 0.02 and P < 0.001, respectively). There was no significant difference between aortic wall uptake at 60 min (SUVmax, 2.15 ± 0.11 SE) and 180 min (SUVmax, 1.99 ± 0.18 SE) (paired t test, P = 0.367). There was a significant difference in lumen uptake at 60 min (SUVmax, 2.4 ± 0.11 SE) and 180 min (SUVmax, 1.7 ± 0.1 SE) (paired t test, P = 0.001). There was no significant difference in TBR between 60 min (0.91 ± 0.03) and 180 min (1.01 ± 0.06 SE) (paired t test, P = 0.131). With increasing delayed imaging, there was increasing variability (SE) in the SUVmax for the aortic wall and TBRs. Conclusion: There was no significant advantage in imaging at 3 h over 1 h after 18F-FDG injection.

Investigating vulnerable atheroma using combined (18)F-FDG PET/CT angiography of carotid plaque with immunohistochemical validation.

Inflammation and angiogenesis are hypothesized to be important factors contributing to plaque vulnerability, whereas calcification is suggested to confer stability. To investigate this in vivo, we combined CT angiography and PET and compared the findings with immunohistochemistry for patients undergoing carotid endarterectomy. Methods: Twenty-one consecutive patients (18 men, 3 women; mean age ± SD, 68.3 ± 7.3) undergoing carotid endarterectomy were recruited for combined carotid 18F-FDG PET/CT angiography. Plaque 18F-FDG uptake was quantified with maximum standardized uptake value, and CT angiography quantified percentage plaque composition (calcium and lipid). Surgical specimens underwent ex vivo CT aiding image registration, followed by immunohistochemical staining for CD68 (macrophage density) and vascular endothelial growth factor (angiogenesis). Relationships between imaging and immunohistochemistry were assessed with Spearman rank correlation and multivariable regression. Results: The mean (±SD) surgically excised carotid plaque 18F-FDG metabolism was 2.4 (±0.5) versus 2.2 (±0.3) contralaterally (P = 0.027). There were positive correlations between plaque 18F-FDG metabolism and immunohistochemistry with CD68 (ρ = 0.55; P = 0.011) and vascular endothelial growth factor (ρ = 0.47; P = 0.031). There was an inverse relationship between plaque 18F-FDG metabolism and plaque percentage calcium composition on CT (ρ = −0.51; P = 0.018) and between calcium composition and immunohistochemistry with CD68 (ρ = −0.57; P = 0.007). Regression showed that maximum standardized uptake value and calcium composition were independently significant predictors of angiogenesis, and calcium composition was a predictor of macrophage density. Conclusion: We provide in vivo evidence that increased plaque metabolism is associated with increased biomarkers of angiogenesis and inflammation, whereas plaque calcification is inversely related to PET and histologic biomarkers of inflammation.

What is the natural history of 18F-FDG uptake in arterial atheroma on PET/CT? Implications for imaging the vulnerable plaque

PURPOSE Increased uptake of 18F-fluorodeoxyglucose (18F-FDG) in atherosclerotic plaque on Positron Emission Tomography (PET), predicts vulnerability. Recent studies have shown that the PET signal is reproducible over a 2-week period and as a result drug trials are underway. However, the natural history of these lesions is unknown. The aim of this study is determine the natural history of increased vascular wall uptake of 18F-fluorodeoxyglucose (18F-FDG). METHODS Following institutional ethics committee approval, we retrospectively examined PET/CT images of patients from our Institution that had at least 4 examinations in the last 5 years. This represented 205 studies in total, from 50 patients (29 men, 21 women, mean age 49.4+/-12.1 years, mean 5.1+/-1.7 studies/patient). The mean follow-up was 27.2+/-11.8 months. The carotids and the aorta were evaluated for increased 18F-FDG uptake with a maximum Standardized Uptake Value (SUVmax)>2.5, and >3.0, and calcification. Plots of SUVmax and Hounsfield units (HU) were made versus time. RESULTS The initial prevalence of increased focal arterial 18F-FDG uptake was 17/50 patients and of arterial calcification 19/50. 132 sites of 18F-FDG uptake in total were observed longitudinally. 18F-FDG vascular uptake did not persist with time. There was no correlation between 18F-FDG uptake and HU. No calcifications developed at sites of focal increased 18F-FDG uptake. CONCLUSIONS Arterial lesions with increased 18F-FDG uptake represent transient phenomena. This data is important for the interpretation of findings of clinical trials using arterial 18F-FDG uptake as an imaging biomarker to monitor pharmacological intervention.

Quantifying the Area at Risk in Reperfused ST-Segment–Elevation Myocardial Infarction Patients Using Hybrid Cardiac Positron Emission Tomography–Magnetic Resonance Imaging

Background—Hybrid positron emission tomography and magnetic resonance allows the advantages of magnetic resonance in tissue characterizing the myocardium to be combined with the unique metabolic insights of positron emission tomography. We hypothesized that the area of reduced myocardial glucose uptake would closely match the area at risk delineated by T2 mapping in ST-segment–elevation myocardial infarction patients. Methods and Results—Hybrid positron emission tomography and magnetic resonance using 18F-fluorodeoxyglucose (FDG) for glucose uptake was performed in 21 ST-segment–elevation myocardial infarction patients at a median of 5 days. Follow-up scans were performed in a subset of patients 12 months later. The area of reduced FDG uptake was significantly larger than the infarct size quantified by late gadolinium enhancement (37.2±11.6% versus 22.3±11.7%; P<0.001) and closely matched the area at risk by T2 mapping (37.2±11.6% versus 36.3±12.2%; P=0.10, R=0.98, bias 0.9±4.4%). On the follow-up scans, the area of reduced FDG uptake was significantly smaller in size when compared with the acute scans (19.5 [6.3%–31.8%] versus 44.0 [21.3%–55.3%]; P=0.002) and closely correlated with the areas of late gadolinium enhancement (R 0.98) with a small bias of 2.0±5.6%. An FDG uptake of ≥45% on the acute scans could predict viable myocardium on the follow-up scan. Both transmural extent of late gadolinium enhancement and FDG uptake on the acute scan performed equally well to predict segmental wall motion recovery. Conclusions—Hybrid positron emission tomography and magnetic resonance in the reperfused ST-segment–elevation myocardial infarction patients showed reduced myocardial glucose uptake within the area at risk and closely matched the area at risk delineated by T2 mapping. FDG uptake, as well as transmural extent of late gadolinium enhancement, acutely can identify viable myocardial segments.Background Hybrid Positron Emission Tomography and Magnetic Resonance (PET-MR) allows the advantages of MR in tissue characterizing the myocardium to be combined with the unique metabolic insights of PET. We hypothesized that the area of reduced myocardial glucose uptake would closely match the area-at-risk (AAR) delineated by T2-mapping in ST-segment elevation myocardial infarction (STEMI) patients.

CT signal heterogeneity of abdominal aortic aneurysm as a possible predictive biomarker for expansion.

OBJECTIVE There is a need for prognostic biomarkers for risk assessment of small abdominal aortic aneurysm (AAA). Since CT textural analysis of tissue is a recognized feature of adverse biology and patient outcome in other diseases, we investigated it as a possible biomarker in small AAA. METHODS Fifty consecutive patients (46-men, 4-woman, median-age 75 y, range 56-85) with small AAA (3-5.5 cm) under surveillance undergoing serial ultrasound were prospectively recruited and assessed at baseline with CT texture analysis (CTTA) and 18F-Fluorodeoxyglucose positron emission tomography (18F-FDG-PET). We followed forty patients (36-men, 4-woman, median-age=74 y, range 60-85, participation rate=80% for 1 year. For each axial image, CTTA using the filtration-histogram technique was carried out using a software algorithm that selectively extracts texture features of different coarseness (fine, medium and coarse) and intensity variation. Standard-deviation (SD) and kurtosis (K) at each feature-scale were measured. The maximum standardized uptake value (SUVmax) of 18F-FDG in each axial image of the AAA was also measured with corrections for blood pool 18F-FDG activity to assess AAA metabolic activity. Specificity, sensitivity, and c-statistics were calculated with 95% confidence intervals for prediction of significant AAA expansion (≥2 mm) by CTTA measures before and after adjusting for clinical variables. RESULTS The median aneurysm expansion at 12 months was 2.0 mm, (IQR 0.0-4.0). Coarse texture SD correlated inversely with AAA SUVmax (rs=-0.456, P=0.003). Medium coarse texture K correlated significantly with future AAA expansion adjusted for baseline size (rs=0.343, P=0.030). AAA SUVmax correlated inversely with AAA expansion corrected for baseline size (rs=-0.383, P=0.015). Medium texture K was a strong predictor of significant AAA expansion (area under the Receiver-operating-characteristic (ROC) curve was 0.813) after adjusting for clinical variables. CONCLUSION We have shown evidence that CT signal heterogeneity measurements in small aortic aneurysm may be considered as a risk stratification tool in future prospective studies to identify aneurysms at risk of significant expansion. CT textural data appears to reflect AAA metabolism measured by PET.

18F-DOPA PET and enhanced CT imaging for congenital hyperinsulinism: initial UK experience from a technologist's perspective.

IntroductionCongenital hyperinsulinism (CHI) is the most common cause of persistent hypoglycaemia in infants and children. Histologically, there are two subgroups, diffuse and focal. The aim of this study was to evaluate the accuracy of 18F-fluoro-L-dihydroxyphenylalanine (18F-DOPA) PET/computed tomography (CT) and contrast-enhanced CT in distinguishing between focal and diffuse lesions in infants with CHI who are unresponsive to medical therapy. In addition, this paper describes the detailed protocol used for imaging and analysis of 18F-DOPA PET/CT images in our clinical practice. Materials and methodsTwenty-two 18F-DOPA PET/CT and contrast-enhanced CT imaging studies were carried out on 18 consecutive patients (nine boys and nine girls) with CHI (median age, 2 years and 1 month; range, 1–84 months) who had positive dominant ABCC8 mutation genetic results or negative ABCC8/t results but did not respond to first-line medical therapy with high-dose diazoxide. 18F-DOPA was produced by the cyclotron unit of Woolfson Molecular Imaging Centre, Manchester, and transported to our centre in central London after synthesis and implementation of quality control measures. 18F-DOPA was administered intravenously at a dose of 4 MBq/kg, and iodine contrast medium was injected intravenously at a dose of 1.5 ml/kg. Single bed position PET/CT images of the pancreas were acquired under light sedation with oral chloral hydrate. Four PET dynamic data acquisition scans were taken 20, 40, 50 and 60 min after injection for a duration of 10 min each. The results were assessed by visual interpretation and quantitative measurements of standardized uptake values (SUVs) in the head, body, and tail of the pancreas. ResultsOf the 18 patients, 13 showed diffuse and five showed focal 18F-DOPA PET pancreatic uptake. Three regions of interest were drawn over the head, body and tail of the pancreas to calculate the SUVmax. Using the formula – highest SUVmax/next highest SUVmax – a ratio was calculated. Five patients had an accumulation of 18F-DOPA in the pancreas and an SUV ratio greater than 1.5, indicating focal disease with an SUVmax more than 50% higher than that of the unaffected areas of the pancreas. The remaining 13 patients had diffuse accumulation of 18F-DOPA in the pancreas (SUV ratio<1.3). Using this ratio, a focal lesion can be distinguished from diffuse uptake and normal pancreatic uptake. The sizes of these regions of interest varied according to the age of the child. All patients diagnosed with focal lesions underwent surgery and were cured eventually. Lesions were accurately localized by PET/CT and confirmed by histological results after surgery. Three of these patients had to undergo second 18F-DOPA scans and second surgeries after unsuccessful excision during their first surgery. Three patients with diffuse disease underwent a partial pancreatectomy, and histological results confirmed diffuse disease. One patient was cured and two remain on high-dose diazoxide therapy because of persistent hypoglycaemia. Conclusion 18F-DOPA PET/CT offers excellent differentiation of focal from diffuse CHI, and the contrast-enhanced CT technique permits precise preoperative localization of the lesion and anatomical landmarks.

135 Novel Hybrid Positron Emission Tomography - Magnetic Resonance (PET-MR) Multi-modality Inflammatory Imaging has Improved Diagnostic Accuracy for Detecting Cardiac Sarcoidosis

Background Cardiac sarcoidosis (CS) is associated with poor outcomes, but detection remains difficult.Few studies evaluate 18-fluorodeoxyglucose positron emission tomography (PET) and cardiac magnetic resonance imaging (MRI) for CS diagnosis. None examine a novel hybrid PET-MR approach. We sought to examine the diagnostic accuracy of hybrid PET-MR imaging for CS detection. Methods 51 consecutive patients with biopsy-proven or clinically suspected CS (age 48 ± 13 years, 32% males) underwent hybrid PET-MR imaging. 18-FDG tracer uptake and late gadolinium enhancement (LGE) were qualitatively assessed on a binary scale and quantitatively by measuring standardised uptake value (SUV) and % LGE detected in each myocardial segment. Sensitivity and specificity of PET-MR for CS diagnosis was calculated. Inter-modality agreement was performed by the Cohen κ method. Coefficient of variance (COV) was performed to determine whether SUV quantification analysis discriminated between CS presence and absence. Results 37 (73%) of the patients had confirmed sarcoidosis; 46% were histologically proven and 59% had cardiac involvement according to JMHW guidelines. FDG uptake on PET-MR was equivalent to PET-CT (p < 0.001), confirming that simultaneous hybrid PET-MR is feasible. When considered in isolation, sensitivity of PET and MR at detecting abnormalities was 0.65 and 0.6, respectively. In contrast, hybrid imaging had improved sensitivity of 0.89 in detecting probable cardiac sarcoidosis with specificity, positive and negative predictive values of 0.42, 0.8 and 0.6, respectively. Sensitivity for detecting confirmed CS using hybrid PET-MR was 100%. Notably, there was poor inter-modality agreement between the location of increased SUV and LGE (k = 0.021). This may reflect the natural history of CS with progression from inflammation to scar and also account for the sensitivity of hybrid imaging. Coefficient of variance analysis of SUV uptake suggested that a COV above 25% predicted CS. Conclusion This is the first study to describe the feasibility and improved diagnostic accuracy of novel hybrid cardiac PET-MR imaging in CS. This technique may allow for more accurate and earlier diagnoses and may also allow titration of therapy according to disease activity.

Inital experience of imaging cardiac sarcoidosis using hybrid PET-MR - a technologist's case study

Background Cardiac imaging has been identified as a potential use of hybrid PET-MRI. This new technology allows simultaneous Positron Emission Tomography (PET) and MR scanning to occur. This case study features a 34 year old male with known pulmonary sarcoidosis which was diagnosed in 2006 and initially treated with immunosuppressants. He presented with NYHA functional class 2 symptoms. ECHO showed asymmetrical LV anterior and lateral wall hypertrophy with a maximum wall thickness of 18mm in the basal and mid anterior and lateral wall. The patient was referred for a cardiac18F Fluorodeoxyglucose (FDG) PET-MR study to determine the cause of the hypertrophy. The possible differential diagnoses included hypertrophic cardiac myopathy with pulmonary sarcoidosis or cardiac sarcoidosis.