Influence of education on cognitive performance and dopamine transporter binding in dementia with Lewy bodies.

OBJECTIVES: Dementia with Lewy bodies (DLB) and Alzheimer's disease (AD) are the two most common forms of dementia. These two diseases share some clinical and pathological similarities, yet the loss of dopaminergic neurons confirmed by 123-I-Ioflupane Single Photon Emission Computed Tomography (SPECT) is a suggestive feature of DLB. Current evidence suggests that higher education has a protective effect on the risk of developing clinical AD. However, how education influences cognitive performance and the presynaptic dopamine transporter marker in DLB is unknown. MATERIALS AND METHODS: We reviewed 56 consecutive patients with DLB who underwent a 123-I-Ioflupane SPECT from January 2009 to August 2013 at the University Hospital of Caen. We collected clinical and neuropsychological data from medical files and 123-I-Ioflupane SPECT data for all patients. RESULTS: There was no correlation between education and global cognitive performance in patients with DLB. However, there was a positive correlation between education and tests exploring visuoconstructive functions (Rey complex figure copy and recall) and verbal retrieval strategies (Grober and Buschke free recall test). There was also a positive correlation between education and dopamine transporter binding. Higher educated patients had higher binding in the striatum, putamen and caudate nucleus (p=0.001 for each regions of interest). Dopamine transporter binding in the striatum, putamen and caudate nucleus was lower in the subgroup of patients with REM sleep behavior disorder, but was not associated with other DLB symptoms. CONCLUSION: Higher education may have a protective effect on visuoconstructive performance and verbal retrieval strategies and may influence dopaminergic nigrostriatal neurodegeneration in patients with DLB.

Potential diagnostic value of regional myocardial adrenergic imaging using (123)I-MIBG SPECT to identify patients with Lewy body diseases.

PURPOSE: The aim of this study was to determine the potential diagnostic value of regional myocardial adrenergic (123)I-metaiodobenzylguanidine (MIBG) single photon emission computed tomography (SPECT) imaging to identify patients with Lewy body diseases (LBD+). METHODS: Sixty-four consecutive patients who underwent cardiac (123)I-MIBG SPECT to differentiate LBD+, including Parkinson's disease (PD) and dementia with Lewy bodies (DLB), from patients without LBD (LBD-) were retrospectively reviewed. A neurologist expert in memory disorders determined the final clinical diagnosis by using international clinical diagnostic criteria. Planar [heart to mediastinum ratio (HMR)] and (123)I-MIBG SPECT[(innervation defect score (IDS)] using the 17-segment left ventricular model (five-point scale) were obtained 4 h after the injection of (123)I-MIBG on a low-energy high-resolution (LEHR) collimator. Receiver-operating characteristic (ROC) analysis was performed to determine the optimal HMR and IDS cut-off values to discriminate LBD+ from LBD-. RESULTS: Of the 64 patients, 45 (70 %) were diagnosed LBD+ (DLB, n = 27; PD, n = 18) and 19 were diagnosed LBD- (5 other dementias, 14 other parkinsonisms). The HMR and IDS of LBD+ were significantly different from those of LBD- (1.30 ± 0.21 vs 1.65 ± 0.26, p < 0.001; 39 ± 28 vs 8 ± 16, p = 0.001). The optimal HMR and IDS cut-off values to discriminate LBD+ (n = 45) from LBD- (n = 19) were 1.47 and 6/68, providing a sensitivity and specificity of 82.2 and 84.2% and 86.7 and 73.7%, respectively. CONCLUSION: Regional myocardial adrenergic (123)I-MIBG imaging SPECT has a potential diagnostic value to identify LBD+.

Towards an optimal semiquantitative approach in giant cell arteritis: an (18)F-FDG PET/CT case-control study.

PURPOSE: Giant cell arteritis (GCA) is the most common form of vasculitis in western countries. (18)F-FDG PET has been shown to be a valuable tool for the diagnosis of extracranial GCA, but results of studies are inconsistent due to a lack of standardized (18)F-FDG PET criteria. In this study, we compared different semiquantitative approaches using a controlled design to define the most efficient method. METHODS: All patients with biopsy-proven GCA who had undergone an (18)F-FDG PET/CT scan in our PET unit were reviewed and matched with a control group based on age and sex. Different semiquantitative arterial (ascending and descending thoracic aorta and aortic arch) to background (liver, lung and venous blood pool) SUV ratios were blindly compared between GCA patients and matched controls. RESULTS: We included 11 patients with biopsy-proven GCA cases and 11 matched controls. There were no differences between the groups with regard to body weight, injected radioactivity, blood glucose level or CRP. The arterial to venous blood pool ratios discriminated the two groups better than other methods when applied to the aortic arch and the descending thoracic aorta (p<0.015). In particular, the highest aortic to highest blood pool SUVmax ratio, when applied to the aortic arch, provided optimal diagnostic performance (sensitivity 81.8 %, specificity 91 %, AUC 0.87; p<0.0001) using a cut-off value of 1.53. CONCLUSION: Among all tested (18)F-FDG PET/CT methods, the aortic to blood pool SUVmax ratio outperformed the liver and lung ratios. We suggest the use of this ratio for the assessment of aortic inflammation in GCA patients.

Diagnostic performance of ¹8F-fluorodeoxyglucose positron emission tomography in giant cell arteritis: a systematic review and meta-analysis.

PURPOSE: The aim of this study was to conduct a systematic review and perform a meta-analysis on the diagnostic performances of (18)F-fluorodeoxyglucose positron emission tomography (FDG PET) for giant cell arteritis (GCA), with or without polymyalgia rheumatica (PMR). METHODS: MEDLINE, Embase and the Cochrane Library were searched for articles in English that evaluated FDG PET in GCA or PMR. All complete studies were reviewed and qualitatively analysed. Studies that fulfilled the three following criteria were included in a meta-analysis: (1) FDG PET used as a diagnostic tool for GCA and PMR; (2) American College of Rheumatology and Healey criteria used as the reference standard for the diagnosis of GCA and PMR, respectively; and (3) the use of a control group. RESULTS: We found 14 complete articles. A smooth linear or long segmental pattern of FDG uptake in the aorta and its main branches seems to be a characteristic pattern of GCA. Vessel uptake that was superior to liver uptake was considered an efficient marker for vasculitis. The meta-analysis of six selected studies (101 vasculitis and 182 controls) provided the following results: sensitivity 0.80 [95% confidence interval (CI) 0.63-0.91], specificity 0.89 (95% CI 0.78-0.94), positive predictive value 0.85 (95% CI 0.62-0.95), negative predictive value 0.88 (95% CI 0.72-0.95), positive likelihood ratio 6.73 (95% CI 3.55-12.77), negative likelihood ratio 0.25 (95% CI 0.13-0.46) and accuracy 0.84 (95% CI 0.76-0.90). CONCLUSION: We found overall valuable diagnostic performances for FDG PET against reference criteria. Standardized FDG uptake criteria are needed to optimize these diagnostic performances.

High throughput static and dynamic small animal imaging using clinical PET/CT: potential preclinical applications.

PURPOSE: The objective of the study was to evaluate state-of-the-art clinical PET/CT technology in performing static and dynamic imaging of several mice simultaneously. METHODS: A mouse-sized phantom was imaged mimicking simultaneous imaging of three mice with computation of recovery coefficients (RCs) and spillover ratios (SORs). Fifteen mice harbouring abdominal or subcutaneous tumours were imaged on clinical PET/CT with point spread function (PSF) reconstruction after injection of [18F]fluorodeoxyglucose or [18F]fluorothymidine. Three of these mice were imaged alone and simultaneously at radial positions -5, 0 and 5 cm. The remaining 12 tumour-bearing mice were imaged in groups of 3 to establish the quantitative accuracy of PET data using ex vivo gamma counting as the reference. Finally, a dynamic scan was performed in three mice simultaneously after the injection of (68)Ga-ethylenediaminetetraacetic acid (EDTA). RESULTS: For typical lesion sizes of 7-8 mm phantom experiments indicated RCs of 0.42 and 0.76 for ordered subsets expectation maximization (OSEM) and PSF reconstruction, respectively. For PSF reconstruction, SOR(air) and SOR(water) were 5.3 and 7.5%, respectively. A strong correlation (r (2) = 0.97, p < 0.0001) between quantitative data obtained in mice imaged alone and simultaneously in a group of three was found following PSF reconstruction. The correlation between ex vivo counting and PET/CT data was better with PSF reconstruction (r (2) = 0.98; slope = 0.89, p < 0.0001) than without (r (2) = 0.96; slope = 0.62, p < 0.001). Valid time-activity curves of the blood pool, kidneys and bladder could be derived from (68)Ga-EDTA dynamic acquisition. CONCLUSION: New generation clinical PET/CT can be used for simultaneous imaging of multiple small animals in experiments requiring high throughput and where a dedicated small animal PET system is not available.

Efficiency of 18F-FDG and 99mTc-depreotide SPECT in the diagnosis of malignancy of solitary pulmonary nodules.

PURPOSE: The purpose of the study was to compare ( 18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET) and ( 99m)Tc-depreotide single-photon emission computed tomography (SPECT) in the diagnosis of malignancy of solitary pulmonary nodules (SPNs). METHODS: Twenty-eight patients without any history of cancer and presenting an SPN (0.8-3 cm in size) underwent FDG PET and depreotide SPECT. Depreotide SPECT and FDG PET were performed on a double-head gamma camera and a dedicated PET scanner respectively. Twenty-five out of 28 lesions were removed by thoracotomy or assessed by biopsy (n=1) and histologically examined. A strategy of serial CT scanning was adopted in the three remaining patients. RESULTS: Histological findings revealed 18 malignant nodules and seven benign lesions. Stability over a 2-year period indicated a benign process in the remaining three cases. Both techniques yielded true positive results in 15 of the 18 cancers. FDG PET identified two additional adenocarcinomas not detected by depreotide SPECT. A carcinoid tumour not visualised on FDG PET was identified by depreotide SPECT. Seven of the ten benign lesions did not reveal tracer uptake on either depreotide SPECT or FDG PET. Both techniques showed false positive results for the same two lesions. One more false positive was seen on FDG PET. FDG PET and depreotide SPECT had a sensitivity of 94.4% and 88.9% respectively; this difference was not significant. In our experience, depreotide SPECT and FDG PET are equally sensitive (92.3%) for large (>1.5 cm) and equally specific (85.7%) for small (up to 1.5 cm) SPNs suspicious for malignancy. CONCLUSION: This study showed( 18)F-FDG PET to be more sensitive than ( 99m)Tc-depreotide SPECT in the diagnosis of malignancy of SPNs. However, the combination of both techniques may provide additional accuracy.

Efficiency of [(18)F]FDG PET in characterising renal cancer and detecting distant metastases: a comparison with CT.

The purpose of this study was to assess the efficiency of fluorine-18 fluoro-2-deoxyglucose (FDG) positron emission tomography (PET) in the characterisation and primary staging of suspicious renal masses, in comparison with computed tomography, the current standard imaging modality. Fifty-three FDG PET studies were performed within the framework of a prospective study: 35 for both characterisation and staging of a suspicious mass, and 18 for staging early after surgical removal of a renal cancer. In the characterisation of renal masses, a high rate of false negative results was observed, leading to a sensitivity, specificity and accuracy of 47%, 80% and 51% respectively, versus 97%, 0/5 and 83% respectively for CT. FDG PET detected all the sites of distant metastasis revealed by CT, as well as eight additional metastatic sites, leading to an accuracy of 94% versus 89% for CT. However, 36/53 patients (68%) did not have any distant metastasis on either CT or on PET. All but one of these patients had a low Fuhrman histological grade and a limited local stage (< or =pT2). We conclude that FDG PET does not offer any advantage over CT for the characterisation of renal masses but that it appears to be an efficient tool for the detection of distant metastasis in renal cancer. However, our data suggest that a selection process could be implemented to determine which patients should undergo PET. FDG PET could be performed in the event of a solitary metastasis or doubtful images on CT. Selection could also be based on adverse histological findings from nephrectomy specimens in order to perform staging early after nephrectomy.

Bioavailability of caseinophosphopeptide-bound iron.

Iron deficiency, one of the main worldwide nutritional deficiencies, results from the low bioavailability of most dietary iron, including cow milk. Hydrolysis of the cow milk protein casein produces low molecular weight caseinophosphopeptides (CPPs). Binding of iron to CPPs keeps it soluble in the digestive tract and prevents the formation of high molecular weight ferric hydroxides, which are poorly absorbed. Previous experimental studies have shown that iron bound to the phosphopeptide containing the first 25 amino acids of beta-casein, or beta-CN (1-25), is well absorbed and corrects efficiently iron deficiency. We sought to assess in vivo iron absorption and uptake by tissues involved in iron metabolism and storage (liver, spleen, bone marrow), using radiolabeled iron. beta-CN (1-25)-Fe displayed better absorption and tissue uptake by the vascularized rat loop model compared with a control substance, ferric ascorbate. The metabolism of beta-CN (1-25)-Fe labeled with iron 59, added to cow milk, was also studied in young women. Although the absorption of beta-CN (1-25)-Fe was not significantly higher than that of ferrous sulfate, it displayed significantly higher tissue uptake. This increase was transient and had disappeared by the 14th day of the study, suggesting that iron was used for metabolic purposes.