José Luis Carreras

Utility of fluorine-18-fluorodeoxyglucose positron emission tomography in differentiated thyroid carcinoma with negative radioiodine scans and elevated serum thyroglobulin levels.

BACKGROUND This study aimed to determine the role of fluorine-18-fluorodeoxyglucose positron emission tomography (FDG-PET) in the follow-up of patients who underwent total thyroidectomy and iodine-131 ((131)I) ablation therapy for differentiated thyroid cancer and presented increased thyroglobulin levels with negative (131)I and thallium-201 ((201)Tl) scans. METHODS Two patients with follicular carcinoma and eight with papillary tumors underwent total thyroidectomy and (131)I therapy until the (131)I scan was negative. (131)I and (201)Tl scans were performed with negative results in all cases, while serum thyroglobulin measurements were all positive with negative thyroglobulin autoantibodies. One week after the (131)I scans, all the patients underwent FDG-PET whole-body scans. RESULTS The FDG-PET scan detected in 4 patients, a single focal increase of FDG uptake in one lymph node metastasis (subsequently confirmed histologically); in 1 patient, multiple pathological focal uptakes in brain, neck, and chest; and in 1 patient, two mild focal uptakes in the mediastinum, close to the tracheal branch. In 2 other patients, pathological FDG uptakes in cervical spine and mediastinum were not confirmed by other imaging techniques, and in the 2 remaining patients the scan results were inconclusive. The sensitivity of FDG-PET whole-body scan for detecting metastatic thyroid cancer was 60%. CONCLUSIONS This study indicates that the FDG-PET whole-body scan is a useful tool in the follow-up of patients with differentiated thyroid cancer, negative (131)I and (201)Tl scans and elevated serum thyroglobulin levels. The FDG-PET scan detects metastatic disease in 60% of patients with differentiated thyroid cancer, enabling surgical therapy to be performed on accessible lesions.

Comparison of different methods of spatial normalization of FDG-PET brain images in the voxel-wise analysis of MCI patients and controls

ObjectiveOne of the most interesting clinical applications of 18F-FDG PET imaging in neurodegenerative pathologies is that of establishing the prognosis of patients with mild cognitive impairment (MCI), some of whom have a high risk of progressing to Alzheimer’s disease (AD). One method of analyzing these images is to perform statistical parametric mapping (SPM) analysis. Spatial normalization is a critical step in such an analysis. The purpose of this study was to assess the effect of using different methods of spatial normalization on the results of SPM analysis of 18F-FDG PET images by comparing patients with MCI and controls.MethodsWe evaluated the results of three spatial normalization methods in an SPM analysis by comparing patients diagnosed with MCI with a group of control subjects. We tested three methods of spatial normalization: MRI-DARTEL and MRI-SPM8, which combine structural and functional images, and FDG-SPM8, which is based on the functional images only.ResultsThe results obtained with the three methods were consistent in terms of the main pattern of functional alterations detected; namely, a bilateral reduction in glucose metabolism in the frontal and parietal cortices in the patient group. However, MRI-SPM8 also revealed differences in the left temporal cortex, and MRI-DARTEL revealed further differences in the left temporal cortex, precuneus, and left posterior cingulate.ConclusionsThe results obtained with MRI-DARTEL were the most consistent with the pattern of changes in AD. When we compared our observations with those of previous reports, MRI-SPM8 and FDG-SPM8 seemed to show an incomplete pattern. Our results suggest that basing the spatial normalization method on functional images only can considerably impair the results of SPM analysis of 18F-FDG PET studies.

Amyloid Proteins and Their Role in Multiple Sclerosis. Considerations in the Use of Amyloid-PeT imaging

Thioflavin T derivatives are used in positron-emission tomography (PET) studies to detect amyloid protein deposits in patients with Alzheimer disease. These tracers bind extensively to white matter, which suggests that they may be useful in studies of multiple sclerosis (MS), and that proteins resulting from proteolytic processing of the amyloid precursor protein (APP) may contribute to MS. This article reviews data from both clinical and preclinical studies addressing the role of these proteins, whether they are detected in CSF studies or using PET imaging. APP is widely expressed in demyelinated axons and may have a protective effect in MS and in experimental allergic encephalomyelitis in animals. Several mechanisms associated with this increased expression may affect the degree of remyelination in MS. Amyloid-PET imaging may help determine the degree of demyelination and provide information on the molecular changes linked to APP proteolytic processing experienced by patients with MS.

Evaluation of the new consensus criteria for the diagnosis of primary progressive aphasia using fluorodeoxyglucose positron emission tomography.

Background: New consensus criteria have been proposed to classify primary progressive aphasia (PPA) into three variants: agrammatic, semantic, and logopenic. Some studies have subsequently addressed the usefulness of these criteria, with controversial results. We aimed to determine the correlation between the clinical diagnosis according to the new criteria and brain topography in 18F-fluorodeoxyglucose positron emission tomography (FDG-PET). Methods: Patients meeting the PPA criteria were prospectively recruited in a single center during a period of 18 months. They were clinically classified according to the new criteria and underwent FDG-PET. The cerebral metabolism of each patient was compared to a healthy control group using statistical parametric mapping. The expected variant according to the analysis of PET imaging was compared with the clinical diagnosis using the consensus criteria. Results: 32 patients were included. 90% of them fulfilled the consensus criteria and could be classified into one of the three clinical variants. The correlation with the cerebral metabolism was high: the kappa index was 0.91 in the agrammatic variant, 0.71 in the semantic variant, and 0.74 in the logopenic variant. Conclusions: A high correlation with the diagnosis obtained using FDG-PET was found. However, an overdiagnosis of the logopenic variant was observed. These results support the use of the new criteria, but some modifications or complementary studies may still be necessary.

18F-FDG PET bio-metabolic monitoring of neoadjuvant therapy effects in rectal cancer: Focus on nodal disease characteristics

OBJECTIVE To evaluate efficacy of (18)F-FDG PET(CT) in the staging and re staging of patients with locally advanced rectal cancer, its potential role in predicting pathological response to neoadjuvant therapy. PATIENTS AND METHODS Patients with confirmed diagnosis of rectal cancer (T2-4 or N+) were prospectively studied with (18)F-FDG PET before and after neoadjuvant therapy. Surgery was programmed 4-6 weeks after treatment followed by an expert histological analysis of the surgical specimen. Response to neoadjuvant treatment was assessed using two specific variables: difference in SUV (difSUV) pre/post-neoadjuvant treatment and response index (RI). RESULTS A total of 64 patients were enrolled for pathological and bio-metabolic response assessment. Compared to cN0, cN+ patients had a higher SUV(1) mean value (6.5 vs. 7.6, p=0.04) and ypN+ patients had higher SUV(2) mean values (2.4 vs 3.5, p=0.06). difSUV values of ≥4 was the most efficient diagnostic parameter (sensitivity=45.8%, specificity=86.2%, positive predictive value (PPV)=73.3%, negative predictive value(NPV)=65.7%). With an RI of 66.6%, the sensitivity was 38.5%, specificity=81.5%, PPV=66.6%, and NPV=57.8%. Patients who experienced disease progression had an RI≤66% and a difSUV≤4. CONCLUSION (18)F-FDG PET has proven to be an accurate diagnostic technique for assessing rectal cancer response to neoadjuvant therapy. The results in terms of sensitivity, specificity, PPV and NPV were similar, if not superior, to those reported with other diagnostic imaging techniques.

Technetium-99m tetrofosmin rest/stress myocardial SPET with a same-day 2-hour protocol: comparison with coronary angiography. A Spanish-Portuguese multicentre clinical trial

Technetium-99m tetrofosmin (Myoview) has unique properties for myocardial perfusion imaging very early after injection of the tracer. We used a very short same-day rest/stress protocol, to be performed within 2 h and evaluated its diagnostic accuracy. The study included 144 patients from seven Spanish and four Portuguese centres with a diagnosis of uncomplicated coronary artery disease (CAD); 78 patients (54%) had no history of prior myocardial infarction. Patients were injected with ≤300 MBq99mTc-tetrofosmin at rest and ≤900 MBq approximately 1 h later at peak exercise. Single-photon emission tomographic (SPET) acquisitions were initiated within 5–30 min post injection. The results were compared with those of coronary angiography (CA). The data of 142 patients were completely evaluable (two with non-evaluable images were excluded). The quality of rest images was excellent or good in 86%, regionally problematic in 7%, poor but well interpretable in 5% and non-evaluable in 2%. The overall sensitivity for the detection of CAD was 93%, the specificity 38% and the accuracy 85%. The localization of defects by SPET in relation to the perfusion territories of stenosed vessels (≽50%) was achieved with a sensitivity of 64% for the left anterior descending artery, 49% for the left circumflex artery and 86% for the right coronary artery, and an accuracy of 71%, 72% and 73% respectively. Concordance of SPET and CA was 62% for single-vessel disease and 68% for multivessel disease. In conclusion, this Spanish-Portuguese multicentre clinical trial confirmed, in a considerable number of patients who underwent coronary angiography, the feasibility of99mTc tetrofosmin (Myoview) rest/stress myocardial SPET using a very short protocol (2 h).

Modification of glucose metabolism in radiation-induced brain injury areas using cervical spinal cord stimulation

PurposeRadiation-induced brain injury (RBI) is an insidious side-effect of radiotherapy mediated by vascular alterations, inflammation and ischaemia. In previous studies we had shown potential increases in loco-regional blood flow and glucose metabolism in brain tumours by using electrical cervical spinal cord stimulation (SCS). In this preliminary report we demonstrate the effect of cervical SCS on RBI-tissue metabolism, as assessed using [18F]fluorodeoxyglucose-positron emission tomography (FDG-PET).MethodsSCS devices were inserted in eight patients with diagnosis of potential RBI in previously irradiated areas. While the SCS device was deactivated, each patient underwent an initial FDG-PET study to evaluate the clinical status. A second FDG-PET study was performed later the same day while the SCS device was activated in order to evaluate the effect of cervical SCS on glucose metabolism.ResultsBasal glucose metabolism in RBI areas was 31% lower than peri-RBI areas (p = 0.009) and 32% lower than healthy contra-lateral areas (p = 0.020). There was a significant increase in glucose uptake during SCS in both the RBI (p = 0.005) and the peri-RBI (p = 0.004) areas, with measured increases of 38 and 42%, respectively. The estimated potential maximal residual activity of the first FDG dose’s contribution to the activity on the second scan was ≤14.3 ± 4.6%.ConclusionsIn this study using PET, SCS increased glucose metabolism in RBI and peri-RBI areas. These results warrant further clinical investigation to elucidate more fully the clinical usefulness of SCS in these patients.

Different apathy clinical profile and neural correlates in behavioral variant frontotemporal dementia and Alzheimer's disease

Apathy is one of the most common and disabling syndromes of dementia. Clinical apathy expression and neuroanatomical basis of apathy seem to differ between behavioral variant frontotemporal dementia (bvFTD) and Alzheimers disease (AD), although evidence is scarce and poorly understood. Our main purposes were to compare the clinical apathy profile from patients with bvFTD and AD and analyze the relationship between apathy and brain metabolism measured using positron emission tomography imaging with 18F fluorodeoxyglucose (FDG‐PET).

Preliminary safety evaluation of a cyclotron facility for positron emission tomography imaging

Abstract. This work describes the design characteristics of a medical imaging centre which uses positron emission tomography, with a cyclotron for fluorine-18 and nitrogen-13 production, and which has provided experimental information on operational data recorded by area dosimetry since 1995. Doses to radiopharmacy and medical staff have been measured both in normal work and in some handling incidents. Data on radiation levels in the installation have also been obtained and related to design details and shielding. Area dosimetry was carried out using a five-stationary detector network, with a sampling rate of 2 min–1, and by thermoluminescent dosimetry (TLD). Staff were also monitored by TLD, using extra chips for finger dosimetry and to duplicate individual whole-body dosimetry in order to measure doses in certain single operations. For normal work, average whole-body doses to radiopharmacy staff were between 0.03 and 0.28 mSv/month, wrist doses were between 0.42 and 2.67 mSv/month, and finger doses were between 1.4 and 7.7 mSv/day for the left hand and 0.8 and 2.4 mSv/day for the right hand; such variation reflects the differing expertise of staff and the role played by optimisation. Finger doses between 16 and 131 mSv were measured in handling incidents, and finger doses of 20.2 and 20.7 mSv for the left hand and 22.0 and 22.3 mSv for the right hand were measured during handling of a syringe without shielding, containing 3 GBq. For medical staff, contributions to the whole-body dose of 2.0 and 1.9 µSv/procedure were measured for injection and placing the patient on the examination couch, respectively. Dose measurement on the middle finger of the right hand gives an average of 70 µSv during the injection. The provisions regarding the shielding design have proved to be adequate and effective during a 3-year operational period. Operational doses to medical staff are comparatively low, while radiopharmacy staff are the most exposed. The finger doses in these professionals may exceed the annual limit, unless operational restrictions in daily practice are adopted. On-line area dosimetry records based on dose rate probes have proved to be effective both for monitoring radiation levels during the operation and for detecting changes in the behaviour of the facility in the irradiation process.

Neural Basis of Cognitive Assessment in Alzheimer Disease, Amnestic Mild Cognitive Impairment, and Subjective Memory Complaints

INTRODUCTION Interpreting cognitive tests is often challenging. The same test frequently examines multiple cognitive functions, and the functional and anatomical basis underlying test performance is unknown in many cases. This study analyses the correlation of different neuropsychological test results with brain metabolism in a series of patients evaluated for suspected Alzheimer disease. METHODS 20 healthy controls and 80 patients consulting for memory loss were included, in which cognitive study and 18F-fluorodeoxyglucose PET were performed. Patients were categorized according to Reisbergs Global Deterioration Scale. Voxel-based analysis was used to determine correlations between brain metabolism and performance on the following tests: Free and Cued Selective Reminding Test (FCSRT), Boston Naming Test (BNT), Trail Making Test, Rey-Osterrieth Complex Figure test, Visual Object and Space Perception Battery (VOSP), and Tower of London (ToL) test. RESULTS Mean age in the patient group was 73.9 ± 10.6 years, and 47 patients were women (58.7%). FCSRT findings were positively correlated with metabolism in the medial and anterior temporal region bilaterally, the left precuneus, and posterior cingulate. BNT results were correlated with metabolism in the middle temporal, superior, fusiform, and frontal medial gyri bilaterally. VOSP results were related to the occipital and parietotemporal regions bilaterally. ToL scores were correlated to metabolism in the right temporoparietal and frontal regions. CONCLUSIONS These results suggest that different areas of the brain are involved in the processes required to complete different cognitive tests. Ascertaining the functional basis underlying these tests may prove helpful for understanding and interpreting them.