Raymond Endozo

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.

Integrated 18F-fluorodeoxyglucose-positron emission tomography/dynamic contrast-enhanced computed tomography to phenotype non-small cell lung carcinoma.

We applied modern molecular and functional imaging to the pretreatment assessment of lung cancer using combined dynamic contrast-enhanced computed tomography (DCE-CT) and 18F-fluorodeoxyglucose–positron emission tomography (18F-FDG-PET) to phenotype tumors. Seventy-four lung cancer patients were prospectively recruited for 18F-FDG-PET/DCE-CT using PET/64-detector CT. After technical failures, there were 64 patients (35 males, 29 females; mean age [± SD] 67.5 ± 7.9 years). DCE-CT yielded tumor peak enhancement (PE) and standardized perfusion value (SPV). The uptake of 18F-FDG quantified on PET as the standardized uptake value (SUVmax) assessed tumor metabolism. The median values for SUVmax and SPV were used to define four vascular-metabolic phenotypes. There were associations (Spearman rank correlation [rs]) between tumor size and vascular-metabolic parameters: SUVmax versus size (rs = .40, p = .001) and SUV/PE versus size (r = .43, p < .001). Patients with earlier-stage (1-HA, n = 30) disease had mean (± SD) SUV/PE 0.36 ± 0.28 versus 0.56 ± 0.32 in later-stage (stage IIB-IV, n = 34) disease (p = .007). The low metabolism with high vascularity phenotype was significantly more common among adenocarcinomas (p = .018), whereas the high metabolism with high vascularity phenotype was more common among squamous cell carcinomas (p = .024). Other non-small cell lung carcinoma tumor types demonstrated a high prevalence of the high metabolism with low vascularity phenotype (p = .028). We show that tumor subtypes have different vascular-metabolic associations, which can be helpful clinically in managing lung cancer patients to hone targeted therapy.

PETCT Imaging of Unstable Carotid Plaque with Ga-68 labelled Somatostatin Receptor Ligand

68Ga-labeled somatostatin receptor ligand PET imaging has recently been shown in preclinical and early human studies to have a potential role in the evaluation of vulnerable arterial plaques. We prospectively evaluated carotid plaque 68Ga-DOTATATE uptake in patients with recent carotid events, assessed inter- and intraobserver variability of such measurements, and explored the mechanism of any plaque DOTATATE activity with immunohistochemistry in resected specimens. Methods: Twenty consecutively consenting patients with recent symptomatic carotid events (transient ischemic attack, stroke, or amaurosis fugax), due for carotid endarterectomy, were prospectively recruited. 68Ga-DOTATATE PET/CT of the neck was performed before surgery. 68Ga-DOTATATE uptake was measured by drawing regions of interest along the carotid plaques and contralateral plaques/carotid arteries by an experienced radionuclide radiologist and radiographer. Two PET quantification methods with inter- and intraobserver variability were assessed. Resected carotid plaques were retrieved for somatostatin receptor subtype-2 (sst2) immunohistochemical staining. Results: The median time delay between research PET and surgery was 2 d. SUVs and target-to-background ratios for the symptomatic plaques and the asymptomatic contralateral carotid arteries/plaques showed no significant difference (n = 19, P > 0.10), regardless of quantification method. The intraclass correlation coefficient was greater than 0.8 in all measures of carotid artery/plaque uptake (SUV) and greater than 0.6 in almost all measures of target-to-background ratio. None of the excised plaques was shown to contain cells (macrophages, lymphocytes, vessel-associated cells) expressing sst2 on their cell membrane. Conclusion: 68Ga-DOTATATE activity on PET in recently symptomatic carotid plaques is not significantly different from contralateral carotids/plaques. Any activity seen on PET is not shown to be from specific sst2 receptor–mediated uptake in vitro. It is therefore unlikely that sst2 PET/CT imaging will have a role in the detection and characterization of symptomatic carotid plaques.

Magnetic resonance-based texture parameters as potential imaging biomarkers for predicting long term survival in locally advanced rectal cancer treated by chemoradiotherapy

The study aimed to investigate whether textural features of rectal cancer on MRI can predict long‐term survival in patients treated with long‐course chemoradiotherapy.

Comparison of rubidium-82 myocardial blood flow quantification with coronary calcium score for evaluation of coronary artery stenosis.

IntroductionPET myocardial perfusion imaging (MPI) is the standard technique for assessing myocardial function, but provides limited information on the anatomy of cardiac structures whereas the coronary artery calcium (CAC) score provides information on calcified plaque burden and the anatomical structure of the coronary arteries. The aim of this study was to determine the relationship between quantitative myocardial blood flow (MBF), CAC, and coronary artery disease (CAD). This work also aims to determine whether MBF quantification and/or CAC add value to relative MPI, and aid in the reclassification of patients with CAD. This way, a ‘gatekeeper’ study could be identified to predict coronary artery stenosis and improve our clinical service. Materials and methodsRubidium-82 PET/CT MPI, calcium score, and computed tomographic coronary angiography imaging were performed in 128 patients with known or suspected CAD. The presence of ischemia was assessed from qualitative reporting of rubidium-82 MPI, and using the same data, quantitative values of MBF and coronary flow reserve (CFR) were derived. Calcium score images were quantitatively analyzed and categorized into three groups defined by CAC values of 0, 1–400, and >400. Significant stenosis was classified as stenosis of 50% or more on computed tomographic angiography. ResultsA total of 120 patients were included in the final analysis (77 men, 43 women). Our results showed an inverse correlation between stress MBF, CFR, and the percentage stenosis as well as an inverse correlation compared with CAC. A direct correlation between CAC and the percentage stenosis was observed, indicating that an increase in coronary calcification in individual coronary arteries is related to the severity of the coronary stenosis. These results proved that the addition of stress MBF to relative MPI (32%) resulted in a significantly higher sensitivity (48%, P=0.002), which increased significantly more with the addition of CFR (58%, P⩽0.001). The further addition of CAC resulted in a significantly higher sensitivity (80%, P=0.001), with an even higher sensitivity with the addition of both CFR and CAC (95%, P⩽0.001) to relative MPI. ConclusionThe addition of quantitative MBF conferred a substantial added diagnostic value to relative MPI for the diagnosis of CAD by highlighting compromised flow with the addition of CAC, increasing this added value even more. We recommend that this approach should be used to predict the presence of coronary artery stenosis at its earliest stage and guide physicians when making decisions on the management pathway of CAD without exposing patients to a high radiation dose during cardiac angiography.

CMR myocardial texture analysis tracks different etiologies of left ventricular hypertrophy

Background Defining the underlying etiology of heart muscle disease is important. Tissue characterisation with late gadolinium enhancement (LGE) and the newer parametric mapping technologies aim to do this. Texture analysis (TA) is another tool that may help. Macroscopic heterogeneity in texture on diagnostic imaging, both at and beyond that appreciated by the human eye, are known to track microscopic histological characteristics in other branches of medicine (computed tomography, oncology). We hypothesised that TA could be 1. translated to CMR cine images and quantify and detect image signal heterogeneity, and 2. the measured signal would track underlying disease etiology.

Improved quantitation and reproducibility in multi-PET/CT lung studies by combining CT information

BackgroundMatched attenuation maps are vital for obtaining accurate and reproducible kinetic and static parameter estimates from PET data. With increased interest in PET/CT imaging of diffuse lung diseases for assessing disease progression and treatment effectiveness, understanding the extent of the effect of respiratory motion and establishing methods for correction are becoming more important. In a previous study, we have shown that using the wrong attenuation map leads to large errors due to density mismatches in the lung, especially in dynamic PET scans. Here, we extend this work to the case where the study is sub-divided into several scans, e.g. for patient comfort, each with its own CT (cine-CT and ‘snap shot’ CT). A method to combine multi-CT information into a combined-CT has then been developed, which averages the CT information from each study section to produce composite CT images with the lung density more representative of that in the PET data. This combined-CT was applied to nine patients with idiopathic pulmonary fibrosis, imaged with dynamic 18F-FDG PET/CT to determine the improvement in the precision of the parameter estimates.ResultsUsing XCAT simulations, errors in the influx rate constant were found to be as high as 60% in multi-PET/CT studies. Analysis of patient data identified displacements between study sections in the time activity curves, which led to an average standard error in the estimates of the influx rate constant of 53% with conventional methods. This reduced to within 5% after use of combined-CTs for attenuation correction of the study sections.ConclusionsUse of combined-CTs to reconstruct the sections of a multi-PET/CT study, as opposed to using the individually acquired CTs at each study stage, produces more precise parameter estimates and may improve discrimination between diseased and normal lung.

Spectrum of metastatic and nonmetastatic skeletal findings with dual-phase 18F-FECH PET/CT in patients with biochemical relapse of prostate cancer

Introduction The aim of this study was to evaluate the spectrum of skeletal findings on dual-phase fluorine-18-fluoroethylcholine (18F-FECH) PET/CT performed during the work-up of patients referred for suspected prostate cancer relapse. Materials and methods Three hundred 18F-FECH PET/CT scans were evaluated prospectively. The low-dose CT features of all cases were categorized as isodense, sclerotic, lytic or mixed lytic/sclerotic and maximum standardized uptake value (SUVmax) values were calculated. Findings on 18F-FECH PET/CT were correlated with Technetium-99m-methylene diphosphonate planar bone scans and serum prostate-specific antigen. Results Patient age range was 50–90 years (median 71 years) and prostate-specific antigen values were in the range 0.04–372 ng/ml (Roche Modular method). Seventy-two lesions were detected on 18F-FECH PET/CT in 45 patients, including 31 (43%) in the pelvis, 17 (23%) in the spine (cervical 3, thoracic 8 and lumbar spine 6) and 10 (13%) in the ribs. Evaluation of low-dose CT in combination with PET helped to characterize benign findings in 21 (29%) lesions. The SUVmax for all except one benign lesion ranged from 0.49 to 2.15. In 51 (71%) lesions because of metastatic disease, SUVmax was 0.6–11.6 for those classified as sclerotic on low-dose CT, 0.7–8.58 for lytic lesions, 1.1–7.65 for isodense lesions and 1.27–3.53 for mixed lytic/sclerotic lesions. Of the 56 18F-FECH-avid lesions, 21 lesions showed avidity on bone scan [3 (23%) of the 13 isodense lesions, 14 (40%) of the 35 sclerotic lesions, 2 (50%) of the lytic lesions and 2 (50%) of the mixed sclerotic/lytic lesions]. Conclusion 18F-FECH PET/CT identified bone lesions in 15% of patients with suspected prostate cancer relapse. SUVmax in isolation cannot be used to characterize these lesions as benign or malignant. Minimal overlap of benign and malignant lesions was observed above SUVmax of 2.5. Low-dose CT of PET/CT is a useful tool to aid characterization.