Assessment of a one-week ketogenic diet on brain glycolytic metabolism and on the status epilepticus stage of a lithium-pilocarpine rat model.

The ketogenic diet (KD) has been shown to be effective in refractory epilepsy after long-term administration. However, its interference with short-term brain metabolism and its involvement in the early process leading to epilepsy remain poorly understood. This study aimed to assess the effect of a short-term ketogenic diet on cerebral glucose metabolic changes, before and after status epilepticus (SE) in rats, by using [18F]-FDG PET. Thirty-nine rats were subjected to a one-week KD (KD-rats, n = 24) or to a standard diet (SD-rats, n = 15) before the induction of a status epilepticus (SE) by lithium-pilocarpine administrations. Brain [18F]-FDG PET scans were performed before and 4 h after this induction. Morphological MRIs were acquired and used to spatially normalize the PET images which were then analyzed voxel-wisely using a statistical parametric-based method. Twenty-six rats were analyzed (KD-rats, n = 15; SD-rats, n = 11). The 7 days of the KD were associated with significant increases in the plasma ß-hydroxybutyrate level, but with an unchanged glycemia. The PET images, recorded after the KD and before SE induction, showed an increased metabolism within sites involved in the appetitive behaviors: hypothalamic areas and periaqueductal gray, whereas no area of decreased metabolism was observed. At the 4th hour following the SE induction, large metabolism increases were observed in the KD- and SD-rats in areas known to be involved in the epileptogenesis process late-i.e., the hippocampus, parahippocampic, thalamic and hypothalamic areas, the periaqueductal gray, and the limbic structures (and in the motor cortex for the KD-rats only). However, no statistically significant difference was observed when comparing SD and KD groups at the 4th hour following the SE induction. A one-week ketogenic diet does not prevent the status epilepticus (SE) and associated metabolic brain abnormalities in the lithium-pilocarpine rat model. Further explorations are needed to determine whether a significant prevention could be achieved by more prolonged ketogenic diets and by testing this diet in less severe experimental models, and moreover, to analyze the diet effects on the later and chronic stages leading to epileptogenesis.

Semi-automated segmentation methods of SSTR PET for dosimetry prediction in refractory meningioma patients treated by SSTR-targeted peptide receptor radionuclide therapy.

OBJECTIVES: Tumor dosimetry with somatostatin receptor-targeted peptide receptor radionuclide therapy (SSTR-targeted PRRT) by 177Lu-DOTATATE may contribute to improved treatment monitoring of refractory meningioma. Accurate dosimetry requires reliable and reproducible pretherapeutic PET tumor segmentation which is not currently available. This study aims to propose semi-automated segmentation methods to determine metabolic tumor volume with pretherapeutic 68Ga-DOTATOC PET and evaluate SUVmean-derived values as predictive factors for tumor-absorbed dose. METHODS: Thirty-nine meningioma lesions from twenty patients were analyzed. The ground truth PET and SPECT volumes (VolGT-PET and VolGT-SPECT) were computed from manual segmentations by five experienced nuclear physicians. SUV-related indexes were extracted from VolGT-PET and the semi-automated PET volumes providing the best Dice index with VolGT-PET (Volopt) across several methods: SUV absolute-value (2.3)-threshold, adaptative methods (Jentzen, Otsu, Contrast-based method), advanced gradient-based technique, and multiple relative thresholds (% of tumor SUVmax, hypophysis SUVmean, and meninges SUVpeak) with optimal threshold optimized. Tumor-absorbed doses were obtained from the VolGT-SPECT, corrected for partial volume effect, performed on a 360° whole-body CZT-camera at 24, 96, and 168 h after administration of 177Lu-DOTATATE. RESULTS: Volopt was obtained from 1.7-fold meninges SUVpeak (Dice index 0.85 ± 0.07). SUVmean and total lesion uptake (SUVmeanxlesion volume) showed better correlations with tumor-absorbed doses than SUVmax when determined with the VolGT (respective Pearson correlation coefficients of 0.78, 0.67, and 0.56) or Volopt (0.64, 0.66, and 0.56). CONCLUSION: Accurate definition of pretherapeutic PET volumes is justified since SUVmean-derived values provide the best tumor-absorbed dose predictions in refractory meningioma patients treated by 177Lu-DOTATATE. This study provides a semi-automated segmentation method of pretherapeutic 68Ga-DOTATOC PET volumes to achieve good reproducibility between physicians. CLINICAL RELEVANCE STATEMENT: SUVmean-derived values from pretherapeutic 68Ga-DOTATOC PET are predictive of tumor-absorbed doses in refractory meningiomas treated by 177Lu-DOTATATE, justifying to accurately define pretherapeutic PET volumes. This study provides a semi-automated segmentation of 68Ga-DOTATOC PET images easily applicable in routine. KEY POINTS: • SUVmean-derived values from pretherapeutic 68Ga-DOTATOC PET images provide the best predictive factors of tumor-absorbed doses related to 177Lu-DOTATATE PRRT in refractory meningioma. • A 1.7-fold meninges SUVpeak segmentation method used to determine metabolic tumor volume on pretherapeutic 68Ga-DOTATOC PET images of refractory meningioma treated by 177Lu-DOTATATE is as efficient as the currently routine manual segmentation method and limits inter- and intra-observer variabilities. • This semi-automated method for segmentation of refractory meningioma is easily applicable to routine practice and transferrable across PET centers.

Functional Alterations Due to COVID-19 Lung Lesions-Lessons From a Multicenter V/Q Scan-Based Registry.

PURPOSE: In coronavirus disease 2019 (COVID-19) patients, clinical manifestations as well as chest CT lesions are variable. Lung scintigraphy allows to assess and compare the regional distribution of ventilation and perfusion throughout the lungs. Our main objective was to describe ventilation and perfusion injury by type of chest CT lesions of COVID-19 infection using V/Q SPECT/CT imaging. PATIENTS AND METHODS: We explored a national registry including V/Q SPECT/CT performed during a proven acute SARS-CoV-2 infection. Chest CT findings of COVID-19 disease were classified in 3 elementary lesions: ground-glass opacities, crazy-paving (CP), and consolidation. For each type of chest CT lesions, a semiquantitative evaluation of ventilation and perfusion was visually performed using a 5-point scale score (0 = normal to 4 = absent function). RESULTS: V/Q SPECT/CT was performed in 145 patients recruited in 9 nuclear medicine departments. Parenchymal lesions were visible in 126 patients (86.9%). Ground-glass opacities were visible in 33 patients (22.8%) and were responsible for minimal perfusion impairment (perfusion score [mean ± SD], 0.9 ± 0.6) and moderate ventilation impairment (ventilation score, 1.7 ± 1); CP was visible in 43 patients (29.7%) and caused moderate perfusion impairment (2.1 ± 1.1) and moderate-to-severe ventilation impairment (2.5 ± 1.1); consolidation was visible in 89 patients (61.4%) and was associated with moderate perfusion impairment (2.1 ± 1) and severe ventilation impairment (3.0 ± 0.9). CONCLUSIONS: In COVID-19 patients assessed with V/Q SPECT/CT, a large proportion demonstrated parenchymal lung lesions on CT, responsible for ventilation and perfusion injury. COVID-19-related pulmonary lesions were, in order of frequency and functional impairment, consolidations, CP, and ground-glass opacity, with typically a reverse mismatched or matched pattern.

Lung Scintigraphy for Pulmonary Embolism Diagnosis in COVID-19 Patients: A Multicenter Study.

In patients with novel coronavirus disease 2019 (COVID-19) referred for lung scintigraphy because of suspected pulmonary embolism (PE), there has been an ongoing debate within the nuclear medicine community as to whether and when the ventilation imaging should be performed. Indeed, whereas PE diagnosis typically relies on the recognition of ventilation-perfusion (V/P) mismatched defects, the ventilation procedure potentially increases the risk of contamination to health-care workers. The primary aim of this study was to assess the role of ventilation imaging when lung scintigraphy is performed because of suspected PE in COVID-19 patients. The secondary aim was to describe practices and imaging findings in this specific population. Methods: A national registry was created in collaboration with the French Society of Nuclear Medicine to collect lung scans performed on COVID-19 patients for suspected PE. The practices of departments were assessed regarding imaging protocols and aerosol precautions. A retrospective review of V/P SPECT/CT scans was then conducted. Two physicians masked to clinical information reviewed each case by sequentially viewing perfusion SPECT, perfusion SPECT/CT, and V/P SPECT/CT images. The scans were classified into 1 of the 4 following categories: patients for whom PE could reasonably be excluded on the basis of perfusion SPECT only, perfusion SPECT/CT, or V/P SPECT/CT and patients with mismatched defects suggestive of PE according to the European Association of Nuclear Medicine criteria. Results: Data from 12 French nuclear medicine departments were collected. Lung scans were performed between March 2020 and April 2021. Personal protective equipment and dedicated cleaning procedures were used in all departments. Of the 145 V/Q SPECT/CT scans included in the central review, PE could be excluded using only perfusion SPECT, perfusion SPECT/CT, or V/P SPECT/CT in 27 (19%), 55 (38%), and 45 (31%) patients, respectively. V/P SPECT/CT was positive for PE in 18 (12%) patients, including 12 (67%) with a low burden of PE (≤10%). Conclusion: In this population of COVID-19 patients assessed with lung scintigraphy, PE could confidently be excluded without the ventilation imaging in only 57% of patients. Ventilation imaging was required to confidently rule out PE in 31% of patients. Overall, the prevalence of PE was low (12%).

Implementation of iMiDEV™, a new fully automated microfluidic platform for radiopharmaceutical production.

iMiDEV™ microfluidic system is a new automated tool for a small-scale production of radiopharmaceuticals. This new radiochemistry module utilizes microfluidic cassettes capable of producing diversified radiopharmaceuticals in liquid phase reactions in an automated synthesizer. The user interface is intuitive and designed to give the operator all the information required and to allow driving the synthesis either manually or fully automatically. In this work, we have demonstrated liquid phase reaction and presented the first results of an efficient fully automated [18F]NaF radiosynthesis on the iMiDEV™ platform. Different parameters such as a type of cyclotron targets, initial activity, concentration and volume of the fluoride-18 targetry have been investigated in order to elaborate the optimised radiolabelling of the ligand. Single and double sodium [18F]fluoride synthesis procedures have been successfully developed using two chambers of the cassette. A single-dose of radiotracer was produced in an average radiochemical yield of 87% (decay corrected) within 8 min and quality control tests were performed as per European Pharmacopoeia.

In vivo characterization of physiological and metabolic changes related to isocitrate dehydrogenase 1 mutation expcression by multiparametric MRI and MRS in a rat model with orthotopically grafted human-derived glioblastoma cell lines.

The physiological mechanism induced by the isocitrate dehydrogenase 1 (IDH1) mutation, associated with better treatment response in gliomas, remains unknown. The aim of this preclinical study was to characterize the IDH1 mutation through in vivo multiparametric MRI and MRS. Multiparametric MRI, including the measurement of blood flow, vascularity, oxygenation, permeability, and in vivo MRS, was performed on a 4.7 T animal MRI system in rat brains grafted with human-derived glioblastoma U87 cell lines expressing or not the IDH1 mutation by the CRISPR/Cas9 method, and secondarily characterized with additional ex vivo HR-MAS and histological analyses. In univariate analyses, compared with IDH1-, IDH1+ tumors exhibited higher vascular density (p < 0.01) and better perfusion (p = 0.02 for cerebral blood flow), but lower vessel permeability (p < 0.01 for time to peak (TTP), p = 0.04 for contrast enhancement) and decreased T1 map values (p = 0.02). Using linear discriminant analysis, vascular density and TTP values were found to be independent MRI parameters for characterizing the IDH1 mutation (p < 0.01). In vivo MRS and ex vivo HR-MAS analysis showed lower metabolites of tumor aggressiveness for IDH1+ tumors (p < 0.01). Overall, the IDH1 mutation exhibited a higher vascularity on MRI, a lower permeability, and a less aggressive metabolic profile. These MRI features may prove helpful to better pinpoint the physiological mechanisms induced by this mutation.

Signs of tracheobronchitis may constitute the principal finding on the lung SPECT/CT images of COVID-19 patients.

BACKGROUND: This study aimed to analyze the rates of tracheobronchitis signs observed on the ventilation scans of COVID-19 patients with shortness of breath, with comparisons to a non-COVID population. METHODS: Lung scintigraphy was collected in 10 such COVID patients, as well as from a non-COVID population investigated outside the epidemic wave period, on a CZT-SPECT/CT system, with ventilation images recorded with 99mTc-labeled Technegas® and perfusion images with 99mTc-labeled albumin macroaggregates. RESULTS: A diffuse tracheobronchial uptake was observed on the ventilation scans from 3 COVID patients (30%), whereas this rate was 3% (3/90) in the non-COVID group (P = 0.013). These 3 patients had no laryngeal extension of Technegas® uptake and limited parenchymal lung abnormalities. Follow-up scintigraphy demonstrated the withdrawal of tracheobronchitis signs in two cases, and the advent of a severe pulmonary embolism in one. CONCLUSION: Signs of tracheobronchitis may constitute the principal finding on lung SPECT/CT images of COVID-19 patients with shortness of breath.

Fully digital PET is unaffected by any deterioration in TOF resolution and TOF image quality in the wide range of routine PET count rates.

PURPOSE: Digital PET involving silicon photomultipliers (SiPM) provides an enhanced time-of-flight (TOF) resolution as compared with photomultiplier (PMT)-based PET, but also a better prevention of the count-related rises in dead time and pile-up effects mainly due to smaller trigger domains (i.e., the detection surfaces associated with each trigger circuit). This study aimed to determine whether this latter property could help prevent against deteriorations in TOF resolution and TOF image quality in the wide range of PET count rates documented in clinical routine. METHODS: Variations, according to count rates, in timing resolution and in TOF-related enhancement of the quality of phantom images were compared between the first fully digital PET (Vereos) and a PMT-based PET (Ingenuity). Single-count rate values were additionally extracted from the list-mode data of routine analog- and digital-PET exams at each 500-ms interval, in order to determine the ranges of routine PET count rates. RESULTS: Routine PET count rates were lower for the Vereos than for the Ingenuity. For Ingenuity, the upper limits were estimated at approximately 21.7 and 33.2 Mcps after injection of respectively 3 and 5 MBq.kg-1 of current 18F-labeled tracers. At 5.8 Mcps, corresponding to the lower limit of the routine count rates documented with the Ingenuity, timing resolutions provided by the scatter phantom were 326 and 621 ps for Vereos and Ingenuity, respectively. At higher count rates, timing resolution was remarkably stable for Vereos but exhibited a progressive deterioration for Ingenuity, respectively reaching 732 and 847 ps at the upper limits of 21.7 and 33.2 Mcps. The averaged TOF-related gain in signal/noise ratio was stable at approximately 2 for Vereos but decreased from 1.36 at 5.8 Mcps to 1.14 and 1.00 at respectively 21.7 and 33.2 Mcps for Ingenuity. CONCLUSION: Contrary to the Ingenuity PMT-based PET, the Vereos fully digital PET is unaffected by any deterioration in TOF resolution and consequently, in the quality of TOF images, in the wide range of routine PET count rates. This advantage is even more striking with higher count-rates for which the preferential use of digital PET should be further recommended (i.e., dynamic PET recording, higher injected activities).

CT abnormalities evocative of lung infection are associated with lower 18F-FDG uptake in confirmed COVID-19 patients.

PURPOSE: CT signs that are evocative of lung COVID-19 infections have been extensively described, whereas 18F-FDG-PET signs have not. Our current study aimed to identify specific COVID-19 18F-FDG-PET signs in patients that were (i) suspected to have a lung infection based on 18F-FDG-PET/CT recorded during the COVID-19 outbreak and (ii) whose COVID-19 diagnosis was definitely established or excluded by appropriate viral testing. METHODS: Twenty-two consecutive patients referred for routine 18F-FDG-PET/CT examinations during the COVID-19 outbreak (March 25th to May 15th 2020) and for whom CT slices were evocative of a lung infection were included in the study. All patients had undergone a SARS-COV-2 diagnostic test to confirm COVID-19 infection (positivity was based on molecular and/or serological tests) or exclude it (negativity of at least the serological test). RESULTS: Eleven patients were confirmed to be affected by COVID-19 (COVID+), whereas the other eleven patients were not (COVID-) and were predominantly suspected of having bacterial pneumonia. CT abnormalities were not significantly different between COVID+ and COVID- groups, although trends toward larger CT abnormalities (p = 0.16) and lower rates of consolidation patterns (0.09) were observed in the COVID+ group. The maximal standardized uptake values (SUVmax) of lung areas with CT abnormalities were however significantly lower in the COVID+ than the COVID- group (3.7 ± 1.9 vs. 6.9 ± 4.1, p = 0.03), with the highest SUVmax consistently not associated with COVID-19. CONCLUSION: Among CT abnormalities evocative of lung infection, those related to COVID-19 are associated with a more limited 18F-FDG uptake. This observation may help improve our ability to detect COVID-19 patients.

Intraindividual comparison of 18 F-FDOPA and 68 Ga-DOTATOC PET/CT detection rate for metastatic assessment in patients with ileal neuroendocrine tumours.

INTRODUCTION: In patients with ileal neuroendocrine tumours (ileal NETs), head-to-head evaluation of diagnostic performances of 68 Ga-DOTA-peptides and 18 F-fluorodihydroxyphenylalanine (18 F-FDOPA) positron emission tomography/computed tomography (PET/CT) has been performed in only few small patients' cohorts. The aim of this retrospective study was to compare 68 Ga-DOTATOC and 18 F-FDOPA PET/CT for metastatic disease assessment in a homogeneous large series of patients with well-differentiated ileal NETs. METHODS: All patients with ileal NETs who underwent both 18 F-FDOPA and 68 Ga-DOTATOC PET/CT within a 3-month period and no therapeutic change between the two studies were retrospectively included. The detection rates of both modalities were calculated using per-patient, per-region and per-lesion analyses. RESULTS: Forty one patients with ileal NETs were evaluated. 18 F-FDOPA and 68 Ga-DOTATOC showed similar detection rates according to per-patient (97% for both) and per-region analyses (94% for 18 F-FDOPA vs 88% for 68 Ga-DOTATOC, P = .35). For a total of 605 positive lesions, 458 (76%) were detected by both modalities, 122 (20%) exclusively by 18 F-FDOPA PET/CT, and 25 (4%) by 68 Ga-DOTATOC PET/CT only. In a per-lesion analysis, 18 F-FDOPA PET/CT performed better than 68 Ga-DOTATOC PET/CT (overall detection rates of 96% vs 80%; P < .001). 18 F-FDOPA PET/CT detected significantly more metastases than 68 Ga-DOTATOC PET/CT in the liver, peritoneum, abdominal and supra-diaphragmatic lymph nodes. CONCLUSION: 18 F-FDOPA PET/CT seems not inferior than 68 Ga-DOTATOC PET/CT for the delineation of metastatic spread of ileal NETs. Therefore, according to local expertise and technical availability, 18 F-FDOPA should be considered as a valid clinical diagnostic option for exhaustive metastatic assessment in patients with ileal NETs. Obviously, 68 Ga-DOTATOC PET/CT remains mandatory for PRRT assessment. Further comparative studies are needed to determine the optimal approach in various clinical scenarios such as preoperative staging and primary tumour detection.

Head-to-head comparison between digital and analog PET of human and phantom images when optimized for maximizing the signal-to-noise ratio from small lesions.

BACKGROUND: Routine PET exams are increasingly performed with reduced injected activities, leading to the use of different image reconstruction parameters than the NEMA parameters, in order to prevent from any deleterious decrease in signal-to-noise ratio (SNR) and thus, in lesion detectability. This study aimed to provide a global head-to-head comparison between digital (Vereos, Philips®) and analog (Ingenuity TF, Philips®) PET cameras of the trade-off between SNR and contrast through a wide-ranging number of reconstruction iterations, and with a further reconstruction optimization based on the SNR of small lesions. METHODS: Image quality parameters were compared between the two cameras on human and phantom images for a number of OSEM reconstruction iterations ranging from 1 to 10, the number of subsets being fixed at 10, and with the further identification of reconstruction parameters maximizing the SNR of spheres and adenopathies nearing 10 mm in diameter. These reconstructions were additionally obtained with and without time-of-flight (TOF) information (TOF and noTOF images, respectively) for further comparisons. RESULTS: On both human and phantom TOF images, the compromise between SNR and contrast was consistently more advantageous for digital than analog PET, with the difference being particularly pronounced for the lowest numbers of iterations and the smallest spheres. SNR was maximized with 1 and 2 OSEM iterations for the TOF images from digital and analog PET, respectively, whereas 4 OSEM iterations were required for the corresponding noTOF images from both cameras. On the TOF images obtained with this SNR optimization, digital PET exhibited a 37% to 44% higher SNR as compared with analog PET, depending on sphere size. These relative differences were however much lower for the noTOF images optimized for SNR (- 4 to + 18%), as well as for images reconstructed according to NEMA standards (- 4 to + 12%). CONCLUSION: SNR may be dramatically higher for digital PET than for analog PET, especially when optimized for small lesions. This superiority is mostly attributable to enhanced TOF resolution and is significantly underestimated in NEMA-based analyses.

A 1-week extension of a ketogenic diet provides a further decrease in myocardial 18F-FDG uptake and a high detectability of myocarditis with FDG-PET.

BACKGROUND: Short periods of fasting and/or low-carbohydrate diet have been proven beneficial for decreasing the myocardial uptake of 18F-fluorodeoxyglucose (18F-FDG) and enhancing the detection of inflammatory heart diseases by 18F-FDG positron emission tomography (PET). This study aimed at determining whether this benefit is increased when a low-carbohydrate ketogenic diet is prolonged up to 7 days. METHODS: Wistar rats underwent serial 18F-FDG-PET imaging after an 18-hour fasting period and after 2, 4 and 7 days of a ketogenic diet (3% carbohydrate) and they were compared to rats submitted to the same protocol but with normal diet (44% carbohydrate). The 18F-FDG-PET/ketogenic protocol was also applied in rats with immune myocarditis (injection of porcine cardiac myosin). RESULTS: The 7-day ketogenic diet was associated with (1) a sustained increase in circulating ketone bodies at an equivalent level to that reached after 18-hour fasting, (2) a gradual decrease in 18F-FDG uptake within normal myocardium reaching a lower level compared to fasting at the 7th day (myocardium-to-blood ratios: 1.68 ± 1.02 vs 3.25 ± 1.40, P < .05) and (3) a high 18F-FDG-PET detectability of myocarditis areas. CONCLUSION: One-week extension of a ketogenic diet provides a further decrease in the 18F-FDG uptake of normal myocardium and a high detectability of inflammatory areas.

C-glyco"RGD" as αIIbß3 and αvß integrin ligands for imaging applications: Synthesis, in vitro evaluation and molecular modeling.

The design of conjugates displaying simultaneously high selectivity and high affinity for different subtypes of integrins is a current challenge. The arginine-glycine-aspartic acid amino acid sequence (RGD) is one of the most efficient short peptides targeting these receptors. We report herein the development of linear and cyclic fluoro-C-glycoside"RGD" conjugates, taking advantage of the robustness and hydrophilicity of C-glycosides. As attested by in vitro evaluation, the design of these C-glyco"RGD" with a flexible three-carbon triazolyl linker allows distinct profiles towards αIIbß3 and αvß3 integrins. Molecular-dynamics simulations confirm the suitability of cyclic C-glyco-c(RGDfC) to target αvß3 integrin. These C-glyco"RGD" could become promising biological tools in particular for Positron Emission Tomography imaging.

Head-to-head comparison of image quality between brain 18F-FDG images recorded with a fully digital versus a last-generation analog PET camera.

BACKGROUND: The quality of phantom images was previously shown to be higher on digital (Vereos Philips®) compared to analog PET (Ingenuity Philips®) cameras. This study aimed to determine the extent to which this difference still remains significant on normal brain 18F-FDG PET images. METHODS: Relative noise and contrast as well as border sharpness (a spatial resolution index) of central (striata) and peripheral (occiput) gray-matter structures were compared between 10 sets of normal brain 18F-FDG PET images recorded and reconstructed on digital and analog last-generation PET cameras, together with a subjective visual analysis of image quality provided by experienced physicians. RESULTS: Compared with analog PET, digital PET provided marked improvements in image quality parameters. The median relative noise was decreased (- 22%), while gray/white-matter contrast was increased (+ 27%/+ 41% for central/peripheral gray-matter structures), with these results being consistent with visual analysis. In addition, a clear enhancement in image sharpness was further documented for digital PET owing to the possible use of a 1-mm3 voxel size (+ 24%/+ 21%). CONCLUSIONS: On normal brain 18F-FDG images and compared with a last-generation analog PET, the fully digital PET camera offers marked improvements in image noise and contrast, as well as significant potential for further enhancing spatial resolution.

Amyloid PETs are commonly negative in suspected Alzheimer's disease with an increase in CSF phosphorylated-tau protein concentration but an Aß42 concentration in the very high range: a prospective study.

BACKGROUND: Atypical cerebrospinal fluid (CSF) patterns, involving an increase in the concentration of phosphorylated-tau (P-tau) proteins but normal amyloid-ß concentration, are not uncommon in patients with mild neurocognitive disorders and suspected Alzheimer's disease (AD). In these conditions, however, AD diagnosis may be ruled out in the absence of any amyloid deposition at positron-emission tomography (PET). This pilot cross-sectional study was aimed to determine whether this negativity of amyloid PET can be predicted by CSF profiles in such patients. METHODS: Twenty-five patients (73 [68-80] years, 10 women) with mild neurocognitive disorders, suspected AD and an increase in the CSF concentration of P-tau proteins but normal Aß42 concentration and Aß42/Aß40 ratio were prospectively included and referred to a 18F-florbetaben PET. The latter was considered as definitively negative with the conjunction of both visual (brain amyloid plaque load score) and quantified (standard uptake value ratios) criteria. Predictors of a negative PET were searched among current CSF biomarkers (Aß42, Aß40, T-tau, P-tau, Aß42/Aß40, Aß42/p-tau). RESULTS: Amyloid PET was negative in 15 patients (60%) with a CSF Aß42 concentration being the sole independent predictor of this negativity. The criterion of an Aß42 concentration in the very high range (> 843 pg/mL), observed in 60% (15/25) of the study patients, was associated with a negative amyloid PET in 93% (14/15) of cases. CONCLUSIONS: In mild neurocognitive disorders patients with suspected AD and showing an increase in CSF P-tau protein level, amyloid PETs are commonly negative, when Aß42 concentration is in the very high range. In such case, AD diagnosis based on biomarkers can be ruled out with reasonable certainty, without the need for additional CSF second-line assays or results from amyloid PET.

Assessment of 18F-Florbetaben Amyloid PET Imaging in Patients with Suspected Alzheimer's Disease and Isolated Increase in Cerebrospinal Fluid Tau Proteins.

BACKGROUND/OBJECTIVE: The aim of this study was to assess, in routine, the rates with which an amyloid deposition was documented by 18F-florbetaben PET in patients with suspected Alzheimer's disease (AD) but with isolated increases in cerebrospinal fluid (CSF) tau-protein concentrations, and the subsequent impact of these PET results on medical management. METHODS: This prospective study included 34 patients with mild neurocognitive disorders (MND) and suspected AD (73±9 years, 16 women) and with abnormal CSF concentrations in total-tau (T-tau) and/or phosphorylated-tau (P-tau) proteins but normal Aß42 concentration and Aß42/Aß40 ratio. These patients were referred to 8F-florbetaben PET from which the PET-related changes in the confidence for AD diagnosis (low, intermediate, or high) and treatments were reported. RESULTS: The PET examinations were positive for amyloid deposition (brain amyloid plaque load, BAPL score >1) in none of the 9 patients with an increase in only T-tau proteins and in 8 among the 25 (32%) with an increase in P-tau proteins (one BAPL score of 2 and seven BAPL scores of 3). Knowledge of the PET results was associated with subsequent changes in diagnostic confidence in 44% of patients (15/34) and in the intention-to-treat with a cholinesterase inhibitor drug in 18% (6/34). CONCLUSION: In patients with suspected AD and isolated increase in CSF tau protein concentrations, an amyloid deposition is documented by 18F-florbetaben PET in as much as one third of cases when the concentration of P-tau is abnormal, and PET results are associated with significant further changes in medical management.

Left ventricular ejection fraction determined with the simulation of a very low-dose CZT-SPECT protocol and an additional count-calibration on planar radionuclide angiographic data.

PURPOSE: To determine whether the left ventricular ejection fractions (EFs), measured on a high-sensitivity CZT single photon emission computed tomography (SPECT)-camera with a 70% reduction in recording times and a prevention of EF overestimation through an additional count-calibration, are concordant with reference EF from planar radionuclide angiography (2D-RNA). METHODS: An additional 10-minute CZT-SPECT recording was performed in patients referred to 2D-RNA for cardiomyopathy (n = 23) or chemotherapy monitoring (n = 50) with an in vivo red blood cell labeling with 850 MBq [Formula: see text]. The EF, obtained from CZT-SPECT with 100% (SPECT100) or 30% (SPECT30) projection times and with a SPECT-count calibration on the 2D-RNA counts of corresponding cavity volumes, were compared to EF from 2D-RNA. RESULTS: Strong and equivalent relationships were documented between the EF from 2D-RNA and the calibrated EF from SPECT100 (y = 0.89x + 6.62; R2 = 0.87) and SPECT30 (y = 0.87x + 8.40; R2 = 0.85), and the mean EF from SPECT100 (54% ± 15%) and SPECT30 (53% ± 16%) were close to that from 2D-RNA (55% ± 15%). However, upward shifts in these mean values were documented in the absence of count calibration for both SPECT100 (60% ± 18%) and SPECT30 (60% ± 18%). CONCLUSION: Left ventricular EF may be determined on a high-sensitivity CZT-camera, a 70% reduction in injected activities, and an additional count-calibration for further enhancing the concordance with 2D-RNA values.

Assessment of Myocardial CZT SPECT Recording in a Forward-Leaning Bikerlike Position.

This prospective randomized study assessed myocardial perfusion imaging with the high-sensitivity D.SPECT cadmium-zinc-telluride camera in a forward-leaning bikerlike position, which may potentially lower diaphragmatic attenuation and reduce breathing-related cardiac motion, in a manner comparable to the prone position proposed with other SPECT cameras. Methods: Patients referred for a stress-rest 99mTc-sestamibi protocol and positioned in the biker position, with the chest leaning forward on the D.SPECT camera-head at 35° from vertical, had an additional resting D.SPECT recording in the supine position (n = 40) or in the sitting position with the back rearward at 30° from vertical (n = 40). Segments with attenuation artifacts were defined as those with less than 65% uptake but with strictly normal contractility at gated SPECT and no defect reversibility from stress images. Results: The biker position was associated with lower heart-to-detector distances than the supine or sitting positions (both P < 0.001); lower cardiac motion amplitudes, assessed on panograms, than the supine position (P < 0.001); and fewer segments with attenuation artifacts than the supine position (on average, 1.10 ± 1.01 vs. 1.90 ± 1.74, P = 0.010) or the sitting position (0.75 ± 0.93 vs. 1.38 ± 1.60, P = 0.011). Conclusion: Myocardial perfusion images from D.SPECT are enhanced for patients positioned in a forward-leaning bikerlike position comparatively to sitting or supine positions, with a notably lower rate of attenuation artifacts.

Compared vulnerabilities to small cardiac motions between different cameras used for myocardial perfusion imaging.

This phantom-based study was aimed to determine whether cardiac CZT-cameras, which provide an enhanced spatial resolution and image contrast compared to Anger cameras, are similarly affected by small cardiac motions. Translations of a left ventricular (LV) insert at half-SPECT acquisitions through six possible orthogonal directions and with 5- or 10-mm amplitude were simulated on the Discovery NM-530c and DSPECT CZT-cameras and on an Anger Symbia T2 camera equipped with an astigmatic (IQ.SPECT) or conventional parallel-hole collimator (Conv.SPECT). SPECT images were initially reconstructed as currently recommended for clinical routine. The heterogeneity in recorded activity from the 17 LV segments gradually increased between baseline and motions simulated at 5- and 10-mm amplitudes with all cameras, although being higher for Anger- than CZT-cameras at each step and resulting in a higher mean number of artifactual abnormal segments (at 10-mm amplitude, Conv.SPECT: 3.7; IQ.SPECT: 1.8, Discovery: 0.7, DSPECT: 0). However, this vulnerability to motion was markedly (1) decreased for Conv.SPECT reconstructed without the recommended Resolution Recovery algorithm and (2) increased for DSPECT reconstructed without the recommended cardiac model. CZT-cameras and especially the DSPECT appear less vulnerable to small cardiac motions than Anger-cameras although these differences are strongly dependent on reconstruction parameters.