Impact of simulated reduced injected dose on the assessment of amyloid PET scans.

PURPOSE: To investigate the impact of reduced injected doses on the quantitative and qualitative assessment of the amyloid PET tracers [18F]flutemetamol and [18F]florbetaben. METHODS: Cognitively impaired and unimpaired individuals (N = 250, 36% Aß-positive) were included and injected with [18F]flutemetamol (N = 175) or [18F]florbetaben (N = 75). PET scans were acquired in list-mode (90-110 min post-injection) and reduced-dose images were simulated to generate images of 75, 50, 25, 12.5 and 5% of the original injected dose. Images were reconstructed using vendor-provided reconstruction tools and visually assessed for Aß-pathology. SUVRs were calculated for a global cortical and three smaller regions using a cerebellar cortex reference tissue, and Centiloid was computed. Absolute and percentage differences in SUVR and CL were calculated between dose levels, and the ability to discriminate between Aß- and Aß + scans was evaluated using ROC analyses. Finally, intra-reader agreement between the reduced dose and 100% images was evaluated. RESULTS: At 5% injected dose, change in SUVR was 3.72% and 3.12%, with absolute change in Centiloid 3.35CL and 4.62CL, for [18F]flutemetamol and [18F]florbetaben, respectively. At 12.5% injected dose, percentage change in SUVR and absolute change in Centiloid were < 1.5%. AUCs for discriminating Aß- from Aß + scans were high (AUC ≥ 0.94) across dose levels, and visual assessment showed intra-reader agreement of > 80% for both tracers. CONCLUSION: This proof-of-concept study showed that for both [18F]flutemetamol and [18F]florbetaben, adequate quantitative and qualitative assessments can be obtained at 12.5% of the original injected dose. However, decisions to reduce the injected dose should be made considering the specific clinical or research circumstances.

Enlarged perivascular spaces and florbetapir uptake in patients with intracerebral hemorrhage.

PURPOSE: Enlarged perivascular spaces in the centrum semiovale (CSO-EPVS) have been linked to cerebral amyloid angiopathy (CAA). To get insight into the underlying mechanisms of this association, we investigated the relationship between amyloid-ß deposition assessed by 18F-florbetapir PET and CSO-EPVS in patients with acute intracerebral hemorrhage (ICH). METHODS: We prospectively enrolled 18 patients with lobar ICH (suggesting CAA) and 20 with deep ICH (suggesting hypertensive angiopathy), who underwent brain MRI and 18F-florbetapir PET. EPVS were assessed on MRI using a validated 4-point visual rating scale in the centrum semiovale and the basal ganglia (BG-EPVS). PET images were visually assessed, blind to clinical and MRI data. We evaluated the association between florbetapir PET positivity and high degree (score> 2) of CSO-EPVS and BG-EPVS. RESULTS: High CSO-EPVS degree was more common in patients with lobar ICH than deep ICH (55.6% vs. 20.0%; p = 0.02). Eight (57.1%) patients with high CSO-EPVS degree had a positive florbetapir PET compared with 4 (16.7%) with low CSO-EPVS degree (p = 0.01). In contrast, prevalence of florbetapir PET positivity was similar between patients with high vs. low BG-EPVS. In multivariable analysis adjusted for age, hypertension, and MRI markers of CAA, florbetapir PET positivity (odds ratio (OR) 6.44, 95% confidence interval (CI) 1.32-38.93; p = 0.03) was independently associated with high CSO-EPVS degree. CONCLUSIONS: Among patients with spontaneous ICH, high degree of CSO-EPVS but not BG-EPVS is associated with amyloid PET positivity. The findings provide further evidence that CSO-EPVS are markers of vascular amyloid burden that may be useful in diagnosing CAA.

Diagnostic value of 99mTc-HMPAO-labeled leukocytes scintigraphy in suspicion of post-sternotomy mediastinitis relapse.

BACKGROUND: The diagnostic value of radiolabeled white blood cells (WBCs) scintigraphy in mediastinitis is well established, but data in the specific context of relapse are lacking. The present study aimed at evaluation of the diagnostic value of WBCs scintigraphy in suspicion of mediastinitis relapse after prior surgical revision. METHODS AND RESULTS: Multiple planar incidences of the chest were acquired 4 and 20 hours after injection of labeled WBC in 43 patients. In case of non-conclusive scintigraphy, a second scan was performed 2-3 weeks after the first one. The diagnosis of infection was based on positive bacteriological results; otherwise patients were followed up for at least 1 year. Out of 39 analyzable patients, 17 (44%) were diagnosed with mediastinitis relapse. After the first scan, 32 of 39 were correctly classified, 2 were false positive, and 5 were not conclusive. After completion of an additional scan in the latter 5 patients, 36 of 39 were correctly classified and 3 were false positive (100% sensitivity, 86% specificity, 85% positive predictive value, and 100% negative predictive value). CONCLUSIONS: In the specific context of suspicion of mediastinitis relapse, the optimal diagnostic value was achieved by repeating the scan when the first one was not conclusive. In this context, a negative WBC scintigraphy was able to rule out infection, with potential major impact on therapeutic management in patients with poor clinical status.

Translocator protein (TSPO) genotype does not change cerebrospinal fluid levels of glial activation, axonal and synaptic damage markers in early Alzheimer's disease.

BACKGROUND: PET imaging of the translocator protein (TSPO) is used to assess in vivo brain inflammation. One of the main methodological issues with this method is the allelic dependence of the radiotracer affinity. In Alzheimer's disease (AD), previous studies have shown similar clinical and patho-biological profiles between TSPO genetic subgroups. However, there is no evidence regarding the effect of the TSPO genotype on cerebrospinal-fluid biomarkers of glial activation, and synaptic and axonal damage. METHOD: We performed a trans-sectional study in early AD to compare cerebrospinal-fluid levels of GFAP, YKL-40, sTREM2, IL-6, IL-10, NfL and neurogranin between TSPO genetic subgroups. RESULTS: We recruited 33 patients with early AD including 16 (48%) high affinity binders, 13 (39%) mixed affinity binders, and 4/33 (12%) low affinity binders. No difference was observed in terms of demographics, and cerebrospinal fluid levels of each biomarker for the different subgroups. CONCLUSION: TSPO genotype is not associated with a change in glial activation, synaptic and axonal damage in early AD. Further studies with larger numbers of participants will be needed to confirm that the inclusion of specific TSPO genetic subgroups does not introduce selection bias in studies and trials of AD that combine TSPO imaging with cerebrospinal fluid biomarkers.

Pharmacological Characterization of [18F]-FNM and Evaluation of NMDA Receptors Activation in a Rat Brain Injury Model.

PURPOSE: NMDA receptors (NMDARs) dysfunction plays a central role in the physiopathology of psychiatric and neurodegenerative disorders whose mechanisms are still poorly understood. The development of a PET (positron emission tomography) tracer able to selectively bind to the NMDARs intra-channel PCP site may make it possible to visualize NMDARs in an open and active state. We describe the in vitro pharmacological characterization of [18F]-fluoroethylnormemantine ([18F]-FNM) and evaluate its ability to localize activated NMDA receptors in a rat preclinical model of excitotoxicity. PROCEDURES: The affinity of the non-radioactive analog for the intra-channel PCP site was determined in a radioligand competition assay using [3H]TCP ([3H]N-(1-[thienyl]cyclohexyl)piperidine) on rat brain homogenates. Selectivity was also investigated by the displacement of specific radioligands targeting various cerebral receptors. In vivo brain lesions were performed using stereotaxic quinolinic acid (QA) injections in the left motor area (M1) of seven Sprague Dawley rats. Each rat was imaged with a microPET/CT camera, 40 min after receiving a dose of 30 MBq + / - 20 of [18F]-FNM, 24 and 72 h after injury. Nine non-injured rats were also imaged using the same protocol. RESULTS: FNM displayed IC50 value of 13.0 ± 8.9 µM in rat forebrain homogenates but also showed significant bindings on opioid receptors. In the frontal and left somatosensory areas, [18F]FNM PET detected a mean of 37% and 41% increase in [18F]FNM uptake (p < 0,0001) 24 and 72 h after QA stereotaxic injection, respectively, compared to the control group. CONCLUSIONS: In spite of FNM's poor affinity for NMDAR PCP site, this study supports the ability of this tracer to track massive activation of NMDARs in neurological diseases.

Clinical heterogeneity of neuro-inflammatory PET profiles in early Alzheimer's disease.

The relationship between neuroinflammation and cognition remains uncertain in early Alzheimer's disease (AD). We performed a cross-sectional study to assess how neuroinflammation is related to cognition using TSPO PET imaging and a multi-domain neuropsychological assessment. A standard uptake value ratio (SUVR) analysis was performed to measure [18F]-DPA-714 binding using the cerebellar cortex or the whole brain as a (pseudo)reference region. Among 29 patients with early AD, the pattern of neuroinflammation was heterogeneous and exhibited no correlation with cognition at voxel-wise, regional or whole-brain level. The distribution of the SUVR values was independent of sex, APOE phenotype, early and late onset of symptoms and the presence of cerebral amyloid angiopathy. However, we were able to demonstrate a complex dissociation as some patients with similar PET pattern had opposed neuropsychological profiles while other patients with opposite PET profiles had similar neuropsychological presentation. Further studies are needed to explore how this heterogeneity impacts disease progression.

Brain Metabolic Profile in Presymptomatic GRN Carriers Throughout a 5-Year Follow-up.

BACKGROUND AND OBJECTIVES: GRN variants are a frequent cause of familial frontotemporal dementia (FTD). Monitoring disease progression in asymptomatic carriers of genetic variants is a major challenge in delivering preventative therapies before clinical onset. This study aimed to assess the usefulness of fluorodeoxyglucose (FDG)-PET in identifying metabolic changes in presymptomatic GRN carriers (PS-GRN+) and to trace their longitudinal progression. METHODS: Participants were longitudinally evaluated over 5 years in a prospective cohort study focused on GRN disease (Predict-PGRN). They underwent cognitive/behavioral assessment, plasma neurofilament measurement, brain MRI, and FDG-PET. Voxel-wise comparisons of structural and metabolic imaging data between 2 groups were performed for each time point. Longitudinal PET changes were evaluated with voxel-wise comparisons and the metabolic percent annual changes method. The association of regional brain metabolism with plasma neurofilament and cognitive changes was analyzed. RESULTS: Among the 80 individuals enrolled in the study, 58 (27 PS-GRN+ and 31 noncarriers) were included in the analyses. Cross-sectional comparisons between PS-GRN+ and controls found a significant hypometabolism in the left superior temporal sulcus (STS) region (encompassing the middle and superior temporal gyri), approximately 15 years before the expected disease onset, without significant cortical atrophy. The longitudinal metabolic decline over the following 5 years peaked around the right STS in carriers (p < 0.001), without significantly greater volume loss compared with that in controls. Their estimated annualized metabolic decrease (-1.37%) was higher than that in controls (-0.21%, p = 0.004). Lower glucose uptake was associated with higher neurofilament increase (p = 0.003) and lower frontal cognitive scores (p = 0.014) in PS-GRN+. DISCUSSION: This study detected brain metabolic changes in the STS region, preceding structural and cognitive alterations, thus contributing to the characterization of the pathochronology of preclinical GRN disease. Owing to the STS involvement in the perception of facially communicated cues, it is likely that its dysfunction contributes to social cognition deficits characterizing FTD. Overall, our study highlights brain metabolic changes as an early disease-tracking biomarker and proposes annualized percent decrease as a metric to monitor therapeutic response in forthcoming trials.

Clinical Effect of Early vs Late Amyloid Positron Emission Tomography in Memory Clinic Patients: The AMYPAD-DPMS Randomized Clinical Trial.

Importance: Amyloid positron emission tomography (PET) allows the direct assessment of amyloid deposition, one of the main hallmarks of Alzheimer disease. However, this technique is currently not widely reimbursed because of the lack of appropriately designed studies demonstrating its clinical effect. Objective: To assess the clinical effect of amyloid PET in memory clinic patients. Design, Setting, and Participants: The AMYPAD-DPMS is a prospective randomized clinical trial in 8 European memory clinics. Participants were allocated (using a minimization method) to 3 study groups based on the performance of amyloid PET: arm 1, early in the diagnostic workup (within 1 month); arm 2, late in the diagnostic workup (after a mean [SD] 8 [2] months); or arm 3, if and when the managing physician chose. Participants were patients with subjective cognitive decline plus (SCD+; SCD plus clinical features increasing the likelihood of preclinical Alzheimer disease), mild cognitive impairment (MCI), or dementia; they were assessed at baseline and after 3 months. Recruitment took place between April 16, 2018, and October 30, 2020. Data analysis was performed from July 2022 to January 2023. Intervention: Amyloid PET. Main Outcome and Measure: The main outcome was the difference between arm 1 and arm 2 in the proportion of participants receiving an etiological diagnosis with a very high confidence (ie, ≥90% on a 50%-100% visual numeric scale) after 3 months. Results: A total of 844 participants were screened, and 840 were enrolled (291 in arm 1, 271 in arm 2, 278 in arm 3). Baseline and 3-month visit data were available for 272 participants in arm 1 and 260 in arm 2 (median [IQR] age: 71 [65-77] and 71 [65-77] years; 150/272 male [55%] and 135/260 male [52%]; 122/272 female [45%] and 125/260 female [48%]; median [IQR] education: 12 [10-15] and 13 [10-16] years, respectively). After 3 months, 109 of 272 participants (40%) in arm 1 had a diagnosis with very high confidence vs 30 of 260 (11%) in arm 2 (P < .001). This was consistent across cognitive stages (SCD+: 25/84 [30%] vs 5/78 [6%]; P < .001; MCI: 45/108 [42%] vs 9/102 [9%]; P < .001; dementia: 39/80 [49%] vs 16/80 [20%]; P < .001). Conclusion and Relevance: In this study, early amyloid PET allowed memory clinic patients to receive an etiological diagnosis with very high confidence after only 3 months compared with patients who had not undergone amyloid PET. These findings support the implementation of amyloid PET early in the diagnostic workup of memory clinic patients. Trial Registration: EudraCT Number: 2017-002527-21.

PET metabolic tumor volume as a new prognostic factor in childhood rhabdomyosarcoma.

PURPOSE: Childhood RMS is a rare malignant disease in which evaluation of tumour spread at diagnosis is essential for therapeutic management. F-18 FDG-PET imaging is currently used for initial RMS disease staging. MATERIALS AND METHODS: This multicentre retrospective study in six French university hospitals was designed to analyse the prognostic accuracy of MTV at diagnosis for patients with RMS between 1 January 2007 and 31 October 2017, for overall (OS) and progression-free survival (PFS). MTV was defined as the sum of the primitive tumour and the largest metastasis, where relevant, with a 40% threshold of the primary tumour SUVmax. Additional aims were to define the prognostic value of SUVmax, SUVpeak, and bone lysis at diagnosis. RESULTS: Participants were 101 patients with a median age of 7.4 years (IQR [4.0-12.5], 62 boys), with localized disease (35 cases), regional nodal spread (43 cases), or distant metastases (23). 44 patients had alveolar subtypes. In a univariate analysis, a MTV greater than 200 cm3 was associated with OS (HR = 3.47 [1.79;6.74], p<0.001) and PFS (HR = 3.03 [1.51;6.07], p = 0.002). SUVmax, SUVpeak, and bone lysis also influenced OS (respectively p = 0.005, p = 0.004 and p = 0.007) and PFS (p = 0.029, p = 0.019 and p = 0.015). In a multivariate analysis, a MTV greater than 200 cm3 was associated with OS (HR = 2.642 [1.272;5.486], p = 0.009) and PFS (HR = 2.707 [1.322;5.547], p = 0.006) after adjustment for confounding factors, including SUVmax, SUVpeak, and bone lysis. CONCLUSION: A metabolic tumor volume greater than 200 cm3, SUVmax, SUVpeak, and bone lysis in the pre-treatment assessment were unfavourable for outcome.

Diagnostic and prognostic value of myocardial perfusion gated SPECT in orthotopic heart transplant recipients.

BACKGROUND: Cardiac allograft vasculopathy (CAV) limits long-term survival after heart transplantation. Diagnostic and prognostic value of gated single photon emission computed tomography (gated SPECT) has not been documented in this setting. METHODS AND RESULTS: We identified 110 consecutive heart transplant recipients (with transplantation >18 months) who underwent stress-rest gated SPECT and coronary angiography within 1 month, and were clinically monitored in a single heart transplantation center. Visual scoring of perfusion and wall motion images used a 16-segment model. Left ventricular function was automatically calculated. Coronary angiography was normal in 64 patients (58%) and abnormal in 46 (any CAV, 42%), of whom 19 had severe stenoses. Sensitivity and negative predictive (NPV) value were .63 and .75 for identification of any CAV, and .84 and .96 for severe CAV. Cox regression analysis showed that independent predictors of cardiac death and retransplantation were the presence of any angiographic CAV lesions (RR = 8.816, P = .043) and a stress perfusion defect >3 segments (RR = 5.607, P = .0053). A stress perfusion defect >3 segments predicted the need for late coronary revascularization >2 months (RR = 6.11, P = .0002). CONCLUSIONS: We conclude that perfusion gated SPECT is a useful noninvasive screening test and may be proposed to help identify heart transplant recipients with a high risk of poor clinical outcome. A normal gated SPECT was associated with a low risk of cardiac hard event and might alleviate the need for coronary angiography.

Contribution and performance of multimodal imaging in the diagnosis and management of cardiac masses.

To evaluate the contribution and performance of multimodal imaging in the diagnostic and therapeutic management of cardiac masses. We carried out a monocentric retrospective study on patients referred for cardiac mass assessment between 2006 and 2019, and analyzed the respective contribution of transesophageal echocardiography (TEE), cardiac computed tomography (CT), cardiac magnetic resonance (CMR) and 18F-fluorodeoxyglucose positron emission tomography coupled with CT (18F-FDG PET-CT). For each test, we determined strategy before and after its completion (need for another imaging or decision-making) as well as result on benign, malignant or indeterminate nature. For the 119 patients included, all imaging modalities increased decision-making rates, which rose from 2 to 54%, 23 to 62%, 31 to 85% and 49 to 100% before and after TEE, CT, CMR and 18F-FDG PET-CT, respectively (P < 0.001 before vs. after). TEE was particularly efficient for atrial masses, especially for the left atrium, with a decision rate rising from 0 to 74% (P < 0.001). 18F-FDG PET-CT was the most efficient to differentiate benign and malignant etiologies (area under the curve 0.89 ± 0.06 and 0.94 ± 0.05 for benign and malignant, respectively, P < 0.001). A benign or undetermined result on each modality was associated with a good prognosis, compared to malignant. All modalities studied are useful for cardiac mass decision-making. First-line TEE is particularly efficient for atrial masses, whereas CT and CMR are useful for ventricular masses or suspicion of malignancy. A benign or malignant result for each modality is correlated to survival and 18F-FDG PET-CT is the most effective to define it.

Myocardial perfusion gated single-photon emission computed tomography in patients with left bundle branch block: comparison between the end-diastolic images and the ungated images.

OBJECTIVES: Septal perfusion abnormalities are frequently observed in patients with left bundle branch block (LBBB). The aim of this study was to compare myocardial perfusion imaging obtained from ungated and diastolic thallium gated single-photon emission computed tomography (SPECT) images in patients with LBBB. METHODS: Stress/rest SPECT was performed in 70 patients with LBBB [38 with coronary artery disease (CAD) (G1), 32 without (G2)] and 19 control participants (G3). Diastolic images were obtained as the sum of four diastolic bins. Perfusion was assessed by summed stress, rest, and difference scores for both diastolic and ungated images. RESULTS: In G1, there was no difference between diastolic and ungated perfusion scores. In G2, summed stress score and summed rest score were increased in diastolic versus ungated imaging, and perfusion defect extent was increased on diastolic versus ungated images at stress (diastole: 6.2 +/- 9.9% vs. ungated: 5.1 +/- 9.70/%, P = 0.01) and rest (diastole: 4.3 +/- 9.3% vs. ungated: 2.8 +/- 9.50%, P = 0.0014), with an increased extent of reversible defect (diastole: 3.4 4.7% vs. ungated: 2.3 3.7%, P = 0.01). In G2, diastolic images failed to correct septal perfusion abnormalities. The number of normal SPECT did not increase with diastolic versus ungated imaging (24 and 180% in G1, 66 and 53% in G2, respectively). Otherwise, a significant association between left ventricular dysfunction and CAD was found, stress ejection fraction being decreased in 20 patients (53%) in G1 and seven patients (22%) in G2 (CHI2 = 6.93, P < 0.01). CONCLUSION: In patients with LBBB, diastolic imaging did not provide additional information to ungated perfusion imaging, but left ventricular dysfunction was associated with CAD.

Weight-loss with activation of brown fat: Suspect pheochromocytoma.

INTRODUCTION: Excess catecholamine stimulates heat production in brown adipose tissue (BAT). Activation of BAT can be detected in patients presenting pheochromocytoma. CASE STUDY: A 58-year-old female patient sought medical advice due to 13 kg weight loss over 2 years accompanied by sweating and high blood pressure. Thoracic-abdominal-pelvic CT-scan revealed a solid 40 mm mass in the left adrenal compartment with peri-adrenal nodules and a solid 80 mm mass at the lower end of the right kidney. 18FDG-PET scan exhibited intense uptake in the supraclavicular, intercostal, mediastinal, peri-renal, mesenteric, iliac and inguinal spaces. Renal tumor with locoregional infiltration and remote metastases was initially considered. Diagnosis of pheochromocytoma was subsequently confirmed by a 10-fold increase in urinary catecholamine, metanephrine and normetanephrine levels. Left adrenalectomy confirmed the diagnosis of pheochromocytoma, with 3 lymph-node metastases in the adjacent adipose tissue surrounded by brown fat. The patient was clinically asymptomatic with normal blood pressure at 3 months post-surgery. A weight gain of 6 kg was recorded, with normalisation of catecholamines/metanephrine/normetanephrine levels. Bilateral peri-renal infiltration (including the right renal mass) disappeared on CT-scan, and TEP-18-FDG no longer showed hypermetabolism. Recurrent mediastinal metastases were diagnosed 6 months after surgery. CONCLUSION: Brown fat activation may mislead diagnosis of pheochromocytoma, suggesting multi-metastatic extra-adrenal tumor, if clinicians are not aware of it.

Prognostic value of sympathetic innervation and cardiac asynchrony in dilated cardiomyopathy.

PURPOSE: The purpose of the study is to examine prognostic values of cardiac I-123 metaiodobenzylguanidine (MIBG) uptake and cardiac dyssynchrony in patients with dilated cardiomyopathy (DCM). MATERIALS AND METHODS: Ninety-four patients with non-ischemic DCM underwent I-123 MIBG imaging for assessing cardiac sympathetic innervation and equilibrium radionuclide angiography. Mean phase angles and SD of the phase histogram were computed for both right ventricular (RV) and left ventricular (LV). Phase measures of interventricular (RV-LV) and intraventricular (SD-RV and SD-LV) asynchrony were computed. RESULTS: Most patients were receiving beta-blockers (89%) and angiotensin-converting enzyme inhibitors (88%). One patient (1%) was lost to follow-up, six had cardiac death (6.4%), eight had heart transplantation (8.6%), and seven had unplanned hospitalization for heart failure (7.5%; mean follow-up: 37 +/- 16 months). Patients with poor clinical outcome were older, had higher The New York Heart Association functional class, impaired right ventricular ejection fraction and left ventricular ejection fraction, and impaired cardiac I-123 MIBG uptake. On multivariate analysis, I-123 MIBG heart-to-mediastinum (H/M) uptake ratio <1.6 was the only predictor of both primary (cardiac death or heart transplantation, RR = 7.02, p < 0.01) and secondary (cardiac death, heart transplantation, or recurrent heart failure, RR = 8.10, p = 0.0008) end points. CONCLUSIONS: In patients receiving modern medical therapy involving beta-blockers, I-123 MIBG uptake, but not intra-LV asynchrony, was predictive of clinical outcome. The impact of beta-blockers on the prognostic value of ventricular asynchrony remains to be clarified.

Frontal Assessment Battery is a marker of dorsolateral and medial frontal functions: A SPECT study in frontotemporal dementia.

The objective of this study is to identify the cerebral regions that are assessed by the Frontal Assessment Battery (FAB). Using SPM voxel-based analysis, we looked for correlations between FAB performance and brain SPECT perfusion in 47 patients with the frontal variant of frontotemporal dementia (fv-FTD) recruited by the French FTD research network, a multicentre initiative of French University hospitals with expertise in the field of dementia. A significant correlation was found between FAB performance and perfusion in the medial and dorsolateral frontal cortex bilaterally, independently of age, gender and MMSE. No correlations were observed with orbital frontal or parietal perfusion, in spite of the presence of hypoperfusion in these areas, or with perfusion of any other cortical or subcortical region. These findings confirm that the FAB is an adequate tool for assessing functions related to the dorsolateral and medial frontal cortex, and is thus useful for the evaluation of diseases associated with frontal dysfunction.

Development and validation of the random walk algorithm: application to the classification of diffuse heterogeneity in brain SPECT perfusion images.

UNLABELLED: Heterogeneity analysis has been studied for radiological imaging, but few methods have been developed for functional images. Diffuse heterogeneous perfusion frequently appears in brain single photon emission computed tomography (SPECT) images, but objective quantification is lacking. An automatic method, based on random walk (RW) theory, has been developed to quantify perfusion heterogeneity. We assess the robustness of our algorithm in differentiating levels of diffuse heterogeneity even when focal defects are present. METHODS: Heterogeneity is quantified by counting R (percentage), the mean rate of visited pixels in a fixed number of steps of the stochastic RW process. The algorithm has been tested on the numerical anthropomorphic Zubal head phantom. Seven diffuse cortical heterogeneity levels were simulated with an adjustable Gaussian function and 6 temporoparietal focal defects simulating Alzheimer Disease, leading to 42 phantoms. Data were projected and smoothed (full width at half maximum, 5.5 mm), and Poisson noise was added to the 64 projections. The SPECT data were reconstructed using filtered backprojection (Hamming filter, 0.5 c/p). R values for different levels of perfusion defect and diffuse heterogeneity were evaluated on 3 parameters: the number of slices studied (20 vs 40), the use of Talairach normalization versus original space, and the use of a cortical mask within the Talairach space. For each parameter, regression lines for heterogeneity and temporoparietal defect quantification were analyzed by covariance statistics. R values were also evaluated on SPECT images performed on 25 subjects with suspected focal dementia and on 15 normal controls. Scans were blindly ranked by 2 experienced nuclear physicians according to the degree of diffuse heterogeneity. RESULTS: Variability of R was smaller than 0.17% for repeated measurements. R was more particularly influenced by diffuse heterogeneity compared with focal perfusion defect. The Talairach normalization had a significant influence on the heterogeneity quantification. The number of slices visited by the RW and the cortical masking have a weak influence on the heterogeneity quantification but only for very low heterogeneity levels. The Spearman coefficient between physicians' consensus and RW automatic ranking is 0.85, in the same order of magnitude as the Spearman coefficient between the rankings of the 2 senior physicians (0.86). CONCLUSIONS: Random walk is an original and objective method and is able to quantify heterogeneous brain perfusion, even in presence of cortical defects. This method is repeatable, robust, and mainly influenced by spatial normalization.

Relevance of functional imaging in dental implantology.

BACKGROUND: Despite it is widely used in many medicine fields, the use of functional imaging to examine dental implants has not been reported in the literature. This work aimed to evaluate the relevance of functional medical imaging in oral implantology. MATERIAL AND METHODS: This single-center observational study was conducted for 6 months at the Toulouse University Hospital, France. All patients who underwent positron emission tomography with 18-fluorodeoxyglucose integrated with X-ray computed tomography (FDG PET/CT) and had dental implants were included. Metabolic activity of the peri-implant tissues was assessed qualitatively and quantitatively jointly by a nuclear physician and a dental surgeon. RESULTS: In 31 patients (121 implants), peri-implant metabolic activity was normal. In 3 patients (4 implants), localized peri-implant hypermetabolism was observed. In all the patients presenting abnormal peri-implant activity, the implants with normal activity were clinicaly and radiogicaly normal, whereas those with hypermetabolism presented peri-implantitis. CONCLUSIONS: This study assess of the relevance of FDG PET/CT in oral implantology. It shows a link between peri-implant hypermetabolism and peri-implantitis. Therefore, FDG PET/CT could become a new tool for the assessment of peri-implant diseases. Key words:Dental implantation, dental implants, peri-implantitis, diagnostic imaging , imaging, three-dimensional, imaging processing, computer-assisted.

18F-Fluorodeoxyglucose positron emission tomography computed tomography detection threshold in follicular lymphoma: A case report.

RATIONALE: Follicular Lymphoma in situ is generally identified as reactive follicular hyperplasia in which some of the hyperplastic germinal centers are colonized by few lymphoma cells. These cells can be detected through their strong 18F-Fluorodeoxyglucose avidity. PATIENT CONCERNS: We report the case of a 70 year-old patient with arthralgia, weight loss and chronic fever over two months. A paraneoplastic polymyalgia rheumatica was initially suspected on abnormal 18F fluoro-deoxyglucose positron emission tomography (PET) pictures in two inguinal lymph nodes with a standardized uptake value at 8.6 and 5.8. DIAGNOSES: The PET lymph nodes were removed and histological examination revealed subtle lymph nodes infiltration by follicular lymphoma in situ. The absolute number of the follicular lymphoma cells determined using virtual imaging and 3D reconstruction appeared very low with a total tumor cell volume estimated at around 0.026 mm for one lymph node and 0.041 mm for the other. INTERVENTIONS: The patient has been treated by corticotherapy alone. OUTCOMES: A long-time follow-up should be highly suggested for this patient to avoid any risk of clinical progression to follicular lymphoma. LESSONS: Our findings show that low amounts of follicular lymphoma cells in reactive germinal center may reach a threshold of hypermetabolism detectable with positron emission tomography imaging, suggesting that tumor microenvironment also accounts for such as strong fluoro-deoxyglucose avidity. Thus, a systematic immunohistochemistry with anti-BCL2 antibodies should be performed on PET positive lymph node with apparent normal morphological features.