Inferior Parietal Cortex Hypoperfusion is the Most Specific Imaging Marker for AD Patients With Positive CSF Biomarker Assays in a Memory Clinic in France.

The diagnostic accuracy of hexamethylpropyleneamine oxime (HMPAo) single-photon emission computed tomography (SPECT) in Alzheimer disease (AD) remains undetermined in a "real-life" clinical population. The objective was to determine the HMPAo SPECT hypoperfusion pattern in cognitively impaired patients with positive CSF AD biomarker and to evaluate its diagnostic accuracy. This study included 120 patients referred to a university memory clinic assessed using HMPAo SPECT, MRI, and CSF biomarkers. Three biomarker signatures suggestive of AD were analyzed (1, Aß1-42; 2, Aß1-42+t-tau and/or p-tau; 3, Aß1-42/p-tau). The clinical diagnoses were possible AD (n=29) or other causes of cognitive impairment (n=91). All CSF AD signatures were significantly (1, P=0.004; 2, P=0.017; 3, P=0.024) associated with the difference between inferior parietal perfusion and lateral dorsal frontal cortex perfusion. The hypoperfusion pattern discriminated between patients with positive CSF AD biomarkers and those with other cognitive impairments with a sensitivity of 67% to 71% and a specificity of 63% to 65% and a greatest negative predictive value (NPV) of 90%. Inferior parietal cortex hypoperfusion was the most sensitive and specific feature in AD patients diagnosed using clinical and CSF biomarker criteria. This hypoperfusion pattern was associated with an NPV of 90% and therefore discriminated sharply between AD and other cognitive disorders.

FDG PET during radiochemotherapy is predictive of outcome at 1 year in non-small-cell lung cancer patients: a prospective multicentre study (RTEP2).

PURPOSE: To assess prospectively the prognostic value of FDG PET/CT during curative-intent radiotherapy (RT) with or without concomitant chemotherapy in patients with non-small-cell lung cancer (NSCLC). METHODS: Patients with histological proof of invasive localized NSCLC and evaluable tumour, and who were candidates for curative-intent radiochemotherapy (RCT) or RT were preincluded after providing written informed consent. Definitive inclusion was conditional upon significant FDG uptake before RT (PET1). All included patients had a FDG PET/CT scan during RT (PET2, mean dose 43 Gy) and were evaluated by FDG PET/CT at 3 months and 1 year after RT. The main endpoint was death (from whatever cause) or tumour progression at 1 year. RESULTS: Of 77 patients preincluded, 52 were evaluable. Among the evaluable patients, 77% received RT with induction chemotherapy and 73% RT with concomitant chemotherapy. At 1 year, 40 patients (77 %) had died or had tumour progression. No statistically significant association was found between stage (IIIB vs. other), histology (squamous cell carcinoma vs. other), induction or concomitant chemotherapy, and death/tumour progression at 1 year. The SUVmax in the PET2 scan was the single variable predictive of death or tumour progression at 1 year (odds ratio 1.97, 95% CI 1.25 - 3.09, p = 0.003) in multivariate analysis. The area under the receiver operating characteristic curve was 0.85 (95% CI 0.73 - 0.94, p < 10(-4)). A SUVmax value of 5.3 in the PET2 scan yielded a sensitivity of 70% and a specificity of 92% for predicting tumour progression or death at 1 year. CONCLUSION: This prospective multicentre study demonstrated the prognostic value in terms of disease-free survival of SUVmax assessed during the 5th week of curative-intent RT or RCT in NSCLC patients (NCT01261598; RTEP2 study).

A study method using early dynamic acquisition of [18F]fluorodopa positron emission tomography for the differential diagnosis between progression and radionecrosis of brain metastases after radiotherapy.

BACKGROUND: It is difficult to distinguish between the brain metastasis progression (BMP) and brain radionecrosis (BRN) on the basis of 18F-3,4-dihydroxyphenylalanine positron emission tomography/computed-tomography (18F-FDOPA PET/CT) data. The advent of silicon photomultiplier (SiPM) PET technology makes it possible to study dynamic volumes and potentially improve diagnostic accuracy. We developed a method for processing 18F-FDOPA PET/CT in the differential diagnosis between BMP and BRN. The method involves a short (3-second) sampling time during a 4-minute acquisition on a SiPM-PET/CT machine. We prospectively included 15 patients and 19 metastases. All acquisitions were performed in list mode acquisition for 25 min on a four-ring SiPM PET/CT system. We calculated the ratios between the maximum activity in the lesion's voxel and the mean activity in the contralateral region (VOImax/CLmean) or the mean activity in the white matter (VOImax/WMmean). RESULTS: Seven lesions were classified as BMP and twelve were classified as BRN. Statistically significant intergroup differences in the VOImax/CLmean and VOImax/WMmean activity ratios were observed for both the clinical volume and the early acquisition. The best performing quantitative variable was the VOImax/CLmean ratio on early acquisition, with a diagnostic accuracy of 94.7%, a sensitivity of 100%, and a specificity of 91.7%. CONCLUSION: The 18F-FDOPA PET/CT data acquired a few minutes after the bolus injection confirms its value in differentiating between BMP and BRN, compared to the much longer classic clinical protocol.

The predictive value of treatment response using FDG PET performed on day 21 of chemoradiotherapy in patients with oesophageal squamous cell carcinoma. A prospective, multicentre study (RTEP3).

PURPOSE: FDG PET has been suggested to have predictive value in the prognosis of oesophageal carcinoma. However, the retrospective studies reported in the literature have shown discordant results. Additionally, only four studies have evaluated FDG PET during chemoradiotherapy (CRT) in patients with different histological lesions. The purpose of this study was to investigate the predictive value of FDG PET performed early during CRT (on day 21) in a population of patients with oesophageal squamous cell carcinoma. METHODS: Included in this prospective study were 57 patients with a histological diagnosis of squamous cell carcinoma of the oesophagus. Of these 57 patients, 48 (84%) were evaluated (aged 63 ± 11 years; 44 men, 4 women). Each patient underwent FDG PET (4.5 MBq/kg) before CRT, according to the Herskovic protocol (t0; PET1) and on day 21 ± 3 from the start of CRT (d21; PET2). The response assessment included a clinical examination, CT scan or FDG PET and histological analysis 3 months and 1 year after PET1. The patients were classified as showing a complete response (CR) or a noncomplete response. A quantitative analysis was carried out for PET1 and PET2 using the following parameters: SUVmax, SUVmean (with SUVmean40 as the 3-D volume at an SUVmax threshold of 40% and SUVmeanp as that defined by a physician), tumour volume (TV, with TV40 defined as the TV at 40% of SUVmax, and TVp as that defined by a physician); and the total lesion glycolysis (TLG, SUVmean × TV, with TLG40 defined as the TLG at 40% of SUVmax, and TLGp as that defined by a physician). The differences in responses at 3 months and 1 year between PET1 (t0) and PET2 (d21) were assessed in terms of variations in SUV, TV and TLG using a repeated measures of variance (ANOVA). RESULTS: SUVmax, SUVmean and TLG decreased significantly between PET1 (t0) and PET2 (d21; p < 0.0001). The TV significantly decreased only when assessed as TVp (p = 0.02); TV40 did not decrease significantly. With respect to the predictive value of PET1, only TV40_1 and TVp_1 values, and therefore TLG40_1 and TLGp_1, but not the SUV values, were significantly lower in patients with CR at 3 months. SUVmax1, TVp_1 and TLGp_1 were significantly lower in patients with CR at 1 year. With respect to the predictive value of PET2, only TV40_2 and TVp_2 values, and therefore TLG40_2 and TLGp_2, but not the SUV values, were significantly lower in patients with CR at 3 months. None of the PET2 parameters had significant value in predicting patient outcome at 1 year. The changes in SUVmax, TV40, TVp, TLG40 and TLGp between PET1 and PET2 had no relationship to patient outcome at 3 months or 1 year. CONCLUSION: This prospective, multicentre study performed in a selected population of patients with oesophageal squamous cell cancer demonstrates that the parameters derived from baseline PET1 are good predictors of response to CRT. Specifically, a high TV and TLG are associated with a poor response to CRT at 3 months and 1 year, and a high SUVmax is associated with a poor response to CRT at 1 year. FDG PET performed during CRT on day 21 appears to have less clinical relevance. However, patients with a large functional TV on day 21 of CRT have a poor clinical outcome (ClinicalTrials.gov NCT 00934505).

Value of Positron Emission Tomography Coupled With Computed Tomography for the Diagnosis of Inflammatory Syndrome of Unknown Origin in an Internal Medicine Department.

Objective: To evaluate the usefulness of positron emission tomography (PET) coupled with computed tomography (CT) in the diagnostic workup for inflammatory syndrome of undetermined origin (IUO) and to determine the diagnostic delay in an internal medicine department. Patients and methods: We retrospectively studied a cohort of patients for whom a PET/CT scan had been prescribed in an indication of IUO in an internal medicine department (Amiens University Medical Center, Amiens, France) between October 2004 and April 2017. The patients were grouped according to the PET/CT findings: very useful (enabling an immediate diagnosis), useful, not useful, and misleading. Results: We analyzed 144 patients. The median (interquartile range) age was 67.7 years (55.8-75.8 years). The final diagnosis was an infectious disease in 19 patients (13.2%), cancer in 23 (16%), inflammatory disease in 48 (33%), and miscellaneous diseases in 12 (8.3%). No diagnosis was made in 29.2% of the cases; half of the remaining had a spontaneously favorable outcome. Fever was observed in 63 patients (43%). Positron emission tomography coupled with CT was determined to be very useful in 19 patients (13.2%), useful in 37 (25.7%), not useful in 63 (43.7%), and misleading in 25 (17.4%). The median diagnostic delay (ie, the time interval between the first admission and a confirmed diagnosis) was significantly shorter in the useful (71 days [38-170 days]) and very useful (55 days [13-79 days]) groups than that in the not useful group (175 days [51-390 days]; P<.001). The median time interval between the PET/CT scan and the diagnosis was twice as long in the not useful group than that in the pooled misleading, useful, or very useful groups (P=.03). In a univariate analysis, the poor overall condition (P=.007) and the absence of fever (P=.005) were predictive of usefulness of PET/CT. Conclusion: Positron emission tomography coupled with CT seems to be useful in the diagnosis of IUO and might shorten the diagnostic delay.

Phantom study of an in-house amplitude-gating respiratory method with silicon photomultiplier technology positron emission tomography/computed tomography.

PURPOSE: The objective of this phantom study was to determine whether breathing-synchronized, silicon photomultiplier (SiPM)-based PET/CT has a suitable acquisition time for routine clinical use. METHODS: Acquisitions were performed in list mode on a 4-ring SiPM-based PET/CT system. The experimental setup consisted of an external respiratory tracking device placed on a commercial dynamic thorax phantom containing a sphere filled with [F-18]-fluorodeoxyglucose. Three-dimensional sinusoidal motion was imposed on the sphere. Data were processed using frequency binning and amplitude binning (the "DMI" and "OFFLINE" methods, respectively). PET sinograms were reconstructed with a Bayesian penalized likelihood algorithm. RESULTS: Respiratory gating from a 150­sec acquisition was successful. The DMI and OFFLINE methods gave similar activity profiles but both were slightly shifted in space; the latter profile was closest to the reference acquisition. CONCLUSION: With SiPM PET/CT systems, the amplitude-based processing of breathing-synchronized data is likely to be feasible in routine clinical practice.

Respiratory-gated 18F-FDG PET imaging in lung cancer: effects on sensitivity and specificity.

BACKGROUND: Respiratory motion is known to deteriorate positron emission tomography (PET) images and may lead to potential diagnostic errors when a standardized uptake value (SUV) cut-off threshold is used to discriminate between benign and malignant lesions. PURPOSE: To evaluate and compare ungated and respiratory-gated 18F-fluorodeoxyglucose PET/computed tomography (CT) methods for the characterization of pulmonary nodules. MATERIAL AND METHODS: The list-mode acquisition during respiratory-gated PET was combined with a short breath-hold CT scan to form the CT-based images. We studied 48 lesions in 43 patients. PET images were analyzed in terms of the maximum SUV (SUV(max)) and the lesion location. RESULTS: Using receiver-operating characteristic (ROC) curves, the optimal SUV cut-off thresholds for the ungated and CT-based methods were calculated to be 2.0 and 2.2, respectively. The corresponding sensitivity values were 83% and 92%, respectively, with a specificity of 67% for both methods. The two methods gave equivalent performance levels for the upper and middle lobes (sensitivity 93%, specificity 62%). They differed for the lower lobes, where the CT-based method outperformed the ungated method (sensitivity values of 90% and 70%, respectively, and a specificity of 73% with both methods) - especially for lesions smaller than 15 mm. CONCLUSION: The CT-based method increased sensitivity and did not diminish specificity, compared with the ungated method. It was more efficient than the ungated method for imaging the lower lobes and smallest lesions, which are most affected by respiratory motion.

Hepatic vascular flow measurements by phase contrast MRI and doppler echography: a comparative and reproducibility study.

PURPOSE: To directly compare and study the variability of parameters related to hepatic blood flow measurements using 3 T phase-contrast magnetic resonance imaging (PC-MRI) and Doppler ultrasound (US). MATERIALS AND METHODS: Nine healthy subjects were studied. Blood velocities and flow rate measurements were performed in the portal vein and the proper hepatic artery. MR studies were performed using a 3 T imager. Gradient-echo fast phase contrast sequences were used with both cardiac and respiratory gating. MR and Doppler flow parameters were extracted and compared. Two methods of calculation were used for Doppler flow rate analysis. RESULTS: Compared to Doppler US, PC-MRI largely underestimated hepatic flow data with lower variability and higher reproducibility. This reproducibility was more pronounced in the portal vein than in the proper hepatic artery associated with poorer velocity correlations. Total hepatic flow values were 1239 +/- 223 mL/min and 1595 +/- 521 mL/min for PC-MRI and Doppler US, respectively. CONCLUSION: Free-breathing PC-MRI can provide reliable noninvasive measurement of hepatic flow parameters compared to Doppler US. The MR technique could help to improve Doppler flow calculations, thereby allowing standardization of protocols, particularly for applications in disease.

A practical way to improve contrast-to-noise ratio and quantitation for statistical-based iterative reconstruction in whole-body PET imaging.

In whole-body positron emission tomography (PET) imaging, the detection of small uptake foci (i.e., around two or three times the tomograph's spatial resolution) is a critical issue. Indeed, spatial resolution is altered by postreconstruction smoothing operations used to reduce the noise introduced by (among other things) an inaccurate system matrix. The authors previously proposed a device-dedicated projector, easily applicable on a clinical gantry, based on point-source measurements, which introduces less noise than a geometrical model. In the present study, they took advantage of the lower noise levels by reducing the postfilter and then quantified the approach's impact on image quality. This study was performed on an IEC Body Phantom Set filled with 18F (sphere-to-background activity ratio: 4:1). The same 3 min acquisition was reconstructed with either (i) a clinical system based on a geometrical tomographic operator (OSEM_CL) or (ii) an OSEM algorithm using the suggested system matrix (OSEM_DR). In order to compare the resulting images, they set the 3D Gaussian postfilter (3DGPF) for OSEM_DR so as to obtain similar background signal-to-noise ratio (SNR) to that of OSEM_CL with a Gaussian postfilter full width at half maximum of 5 mm (as recommended for whole-body imaging on a Biograph6). They then assessed the contrast-to-noise ratio (CNR) and quantitation [contrast recovery (CR)] for the phantom's four smallest spheres (with internal diameters of 10, 13, 17, and 22 mm). Evaluation of 3DGPFs ranging from 2.2 to 2.6 mm showed that a value of 2.4 mm in OSEM_DR gave the closest background SNR to that of OSEM_CL with a 3DGPF of 5 mm. For all studied targets, the CNR was higher with OSEM_DR than with OSEM_CL. For the 10 and 13 mm spheres, OSEM_DR increased the size of the CNR peaks by 37% and 20%, relative to OSEM_CL. The OSEM_DR technique yielded higher CR values than OSEM_CL did. For the 10, 13, 17, and 22 mm spheres, the CR values at eight iterations were 0.5, 0.6, 1.1, and 1.0 for OSEM_DR and 0.3, 0.4, 0.9, and 0.8 for OSEM_CL. They evaluated a practical method for determining a device-dedicated system matrix based on point-source acquisitions. This tomographic operator is more realistic than geometrical system matrix and introduces less noise into PET images during statistical reconstruction; it thus reduces the extent of postfiltering operations required. Thus, spatial resolution is better maintained with OSEM_DR than with clinical reconstruction. They showed that this method improves the contrast-to-noise ratio and quantification of uptake foci (especially those that are at the system's limit of detection) and, in a clinical context, could allow better detection and earlier diagnosis.

Comparison of two commercial whole body PET systems based on LSO and BGO crystals respectively for brain imaging.

The prevalence of neurodegenerative diseases is growing in western countries and PET imaging is increasingly frequently used for clinical and research purposes. However, few PET cameras are dedicated to cerebral imaging. The Biograph 6 (Biograph6) (Siemens Medical Solutions) is a PET/CT dedicated to high throughput whole body studies. Its performance for cerebral imaging has not yet been assessed. The aims of this study were to compare the quantification and detectability of the Biograph for cerebral imaging with those of a well-validated PET camera, the ECAT EXACT HR+ (HR+) (Siemens Medical Solutions). A phantom measuring 19 cm long and 20 cm in diameter was filled with a 18F-fluorodeoxyglucose (18F-FDG) solution. Two 5.7 and 20 ml spheres filled with water (cold-spots), three 0.25 ml spheres (sphere-to-background: 3, 6, and 12), one 1.14 ml sphere (sphere-to-background: 3), and one 11.27 ml sphere (sphere-to-background: 2) filled with a radioactive solution were inserted into the phantom. The activity concentration was chosen so that the count rates for the phantom measurements matched those of typical brain studies on both cameras. Images were reconstructed using FORE and OSEM algorithms. The reconstruction parameters were adjusted to obtain a similar signal-to-noise ratio in images acquired with the two cameras. The contrast recovery (CR) coefficients were similar on the two scanners for the 5.7 and 20 ml spheres (cold spheres) and the 1.14 and 11.27 ml spheres (hot spheres). For the 0.25 ml spheres, the CR values were 35% higher for the sphere-to-background ratio of 12 and 39% higher for the sphere-to-background ratio of 6 on the Biograph6 for the 3 min scan. The variability of measurements was lower on the Biograph6 than on the HR+. The detectability for the smallest spheres on the Biograph6 was close to that on the HR+. The Biograph has similar performances as the HR+ reference tomograph for the detection and quantification of small hot spots and cold spots.

Initial clinical results for breath-hold CT-based processing of respiratory-gated PET acquisitions.

PURPOSE: Respiratory motion causes uptake in positron emission tomography (PET) images of chest structures to spread out and misregister with the CT images. This misregistration can alter the attenuation correction and thus the quantisation of PET images. In this paper, we present the first clinical results for a respiratory-gated PET (RG-PET) processing method based on a single breath-hold CT (BH-CT) acquisition, which seeks to improve diagnostic accuracy via better PET-to-CT co-registration. We refer to this method as "CT-based" RG-PET processing. METHODS: Thirteen lesions were studied. Patients underwent a standard clinical PET protocol and then the CT-based protocol, which consists of a 10-min List Mode RG-PET acquisition, followed by a shallow end-expiration BH-CT. The respective performances of the CT-based and clinical PET methods were evaluated by comparing the distances between the lesions' centroids on PET and CT images. SUV(MAX) and volume variations were also investigated. RESULTS: The CT-based method showed significantly lower (p = 0.027) centroid distances (mean change relative to the clinical method = -49%; range = -100% to 0%). This led to higher SUV(MAX) (mean change = +33%; range = -4% to 69%). Lesion volumes were significantly lower (p = 0.022) in CT-based PET volumes (mean change = -39%: range = -74% to -1%) compared with clinical ones. CONCLUSIONS: A CT-based RG-PET processing method can be implemented in clinical practice with a small increase in radiation exposure. It improves PET-CT co-registration of lung lesions and should lead to more accurate attenuation correction and thus SUV measurement.

Improved attenuation correction via appropriate selection of respiratory-correlated PET data.

PURPOSE: We propose a respiratory-correlated PET data processing method (called "BH-CT-based") based on breath-hold CT acquisition to reduce the smearing effect and improve the attenuation correction. The resulting images are compared with the ungated PET images acquired using a standard, free-breathing clinical protocol. METHODS: The BH-CT-based method consisted of a list-mode acquisition with simultaneous respiratory signal recording. An additional breath-hold CT acquisition was also performed in order to define a tissue position from which PET events can be selected. A phantom study featured a 0.5-ml sphere (filled with 18F-fluorodeoxyglucose ((18)F-FDG) solution) pushed onto a rubber balloon (filled with (18)F-FDG solution and iodinated contrast agent). The feasibility of the BH-CT-based method was also assessed in two patients. RESULTS: In the phantom study, the contrast-to-noise ratios (CNRs) were -1.6 for the Ungated volume and 5.1 for the BH-CT-based volume. For patients, CNRs were higher for BH-CT-based volumes than those for Ungated volumes (17.3 vs. 6.3 and 7.3 vs. 3.8, for patients 1 and 2, respectively). Bias-variance measurements were performed and yielded bias reduction of 40% with BH-CT-based. CONCLUSION: The application of a BH-CT-based method decreases motion bias in PET images. This method resolves issues related to both PET-to-CT misregistration and erroneous attenuation correction and increases lesion detectability.

Benefits of respiratory-gated 18F-FDG PET acquisition in lung disease.

BACKGROUND: Fluorine-18-fluorodeoxyglucose (F-FDG) PET/computed tomography (CT) is a reliable imaging modality for the diagnosis of malignant lung nodules and to assess the latter's prognosis. However, physiological respiratory motion deteriorates PET images and thus decreases the technique's diagnostic and prognostic values. This issue can be overcome by applying respiratory gating to the F-FDG PET/CT acquisitions. PURPOSE: The aim of this study was to evaluate the ability of respiratory-gated F-FDG PET/CT to diagnose malignant lung nodules and to predict recurrence and patient survival. PATIENTS AND METHODS: A total of 103 prospectively enrolled patients with solid lung nodules underwent both ungated and gated F-FDG PET/CT acquisitions. The maximum standardized uptake value (SUVmax) was used to differentiate benign from malignant nodules. Patients have been followed up for at least 36 months to confirm imaging results and assess survival. RESULTS: Gated F-FDG PET/CT was significantly more sensitive than ungated PET/CT for the diagnosis of malignant lung nodules located in the lower lobes (92 vs. 58%; P<0.001) and in patients aged older than 60 years (73 vs. 48%; P<0.001). The same gain was observed for stage I cancers with tumors from 10 to 20 mm. When considering patients aged older than 60 years, those with a low SUVmax on gated PET images had a significantly higher 3-year disease-free survival rate than those with a high SUVmax (76 vs. 47%; P=0.03). CONCLUSION: F-FDG PET/CT is advisable for the assessment of lung nodules in patients aged older than 60 years and/or in the lower lobes.

Aging effects on cerebral blood and cerebrospinal fluid flows.

Phase-contrast magnetic resonance imaging (PC-MRI) is a noninvasive reliable technique, which enables quantification of cerebrospinal fluid (CSF) and total cerebral blood flows (tCBF). Although it is used to study hydrodynamic cerebral disorders in the elderly group (hydrocephalus), there is no published evaluation of aging effects on both tCBF and CSF flows, and on their mechanical coupling. Nineteen young (mean age 27+/-4 years) and 12 elderly (71+/-9 years) healthy volunteers underwent cerebral MRI using 1.5 T scanner. Phase-contrast magnetic resonance imaging pulse sequence was performed at the aqueductal and cervical levels. Cerebrospinal fluid and blood flow curves were then calculated over the cardiac cycle, to extract the characteristic parameters: mean and peak flows, their latencies, and stroke volumes for CSF (cervical and aqueductal) and vascular flows. Total cerebral blood flow was (P<0.01) decreased significantly in the elderly group when compared with the young subjects with a linear correlation with age observed only in the elderly group (R(2)=0.7; P=0.05). Arteriovenous delay was preserved with aging. The CSF stroke volumes were significantly reduced in the elderly, at both aqueductal (P<0.01) and cervical (P<0.05) levels, whereas aqueduct/cervical proportion (P=0.9) was preserved. This is the first work to study aging effects on both CSF and vascular cerebral flows. Data showed (1) tCBF decrease, (2) proportional aqueductal and cervical CSF pulsations reduction as a result of arterial loss of pulsatility, and (3) preserved intracerebral compliance with aging. These results should be used as reference values, to help understand the pathophysiology of degenerative dementia and cerebral hydrodynamic disorders as hydrocephalus.

A new lumped-parameter model of cerebrospinal hydrodynamics during the cardiac cycle in healthy volunteers.

Our knowledge of cerebrospinal fluid (CSF) hydrodynamics has been considerably improved with the recent introduction of phase-contrast magnetic resonance imaging (phase-contrast MRI), which can provide CSF and blood flow measurements throughout the cardiac cycle. Key temporal and amplitude parameters can be calculated at different sites to elucidate the role played by the various CSF compartments during vascular brain expansion. Most of the models reported in the literature do not take into account CSF oscillation during the cardiac cycle and its kinetic energy impact on the brain. We propose a new lumped-parameter compartmental model of CSF and blood flows in healthy subjects during the cardiac cycle. The system was divided into five submodels representing arterial blood, venous blood, ventricular CSF, cranial subarachnoid space, and spinal subarachnoid space. These submodels are connected by resistances and compliances. The model developed was used to reproduce certain functional characteristics observed in seven healthy volunteers, such as the distribution (amplitude and phase shift) of arterial, venous, and CSF flows. The results show a good agreement between measured and simulated intracranial CSF and blood flows.

Effect of tomographic operator inaccuracies and respiratory motion on PET/CT lung nodule images smearing.

BACKGROUND: In thoracic PET/computed tomography (CT) imaging, uptake foci usually appear smeared because of postreconstruction smoothing and respiratory motion. OBJECTIVE: The aim of the present study was to assess the respective contributions of the reconstruction process and respiratory motion on PET/CT images. MATERIALS AND METHODS: Thirty-one pulmonary lesions were studied. Free-breathing PET/CT acquisitions were followed by a 10-min respiratory-gated PET/CT acquisition. Four different reconstructions were performed by combining two different tomographic operators (TOs) (i.e. the geometric clinical system matrix or a system matrix including the detector response) and taking account (or not) of respiratory motion using a previously developed 'CT-based' technique. For each reconstruction method, lesion segmentation was performed with an adaptive threshold. Next, we computed the volume differences between each reconstruction. Finally, we applied a multiple linear model to compute the relative contributions of TO-based and CT-based respiratory compensation to lesion volume. RESULTS: The three groups, combining the reconstruction methods and the respiratory compensation (or not), differed significantly in terms of the volume differences. For all lesions, the full linear model yielded a regression coefficient R of 76.10%. The partial R values were 65.58 and 10.52% for the detector response operator and the CT-based method, respectively. For lesions in the upper/middle lobes, blurring was mainly because of TO (partial R=78.53%), whereas, for lower lobe lesions, smearing was mainly because of respiratory motion (partial R=56.76%). CONCLUSION: Our results showed that image reconstruction, by TO accuracy, was the main explanatory factor for lesion smearing when considering the chest as a whole. Respiration had a major impact on the lower lobes.

Use of dynamic (18)F-fluorodeoxyglucose positron emission tomography to investigate choroid plexus function in Alzheimer's disease.

Choroid plexuses (CPs) are structures involved in CSF production and cerebral regulation and present atypical glucose metabolism. In addition, CPs impairment may be related to Alzheimer disease (AD). In the present study, we present the first results pointing out glucose metabolism in the CP with dynamic fluorodeoxyglucose positron emission tomography (dynamic (18)F-FDG-PET). We studied 47 elderly adults who were classified into three classes: healthy subjects (HS), amnestic mild cognitive impairment (aMCI) and AD. All participants have undergone dynamic (18)F-FDG-PET for 45 min. Acquisitions were divided into 34 frames to extract tissue time-activity curves (TTACs) in various structures including CSF and CPs. Results showed a decreased CPs (18)F-FDG metabolism in AD compared with aMCI and HS. Conversely, dynamic uptake was higher in CSF for AD compared with the other groups. ROC analysis showed that CPs TTACs are a promising tool as it yielded sensitivity of 85.7% and a specificity of 83.3%. Our study showed a disturbance of glucose exchange at the blood-CSF barrier level which is in favour of a key-role of the CPs in AD.

What are the Most Frequently Impaired Markers of Neurodegeneration in ADNI Subjects?

The aim of this study was to examine the relationship between cerebrospinal fluid (CSF) levels of biomarkers for Alzheimer's disease (AD) (Aß1-42, t-tau, and p-tau) and 18Fluorodeoxyglucose positron emission tomography (FDG-PET) hypometabolism in subjects from the Alzheimer's Disease Neuroimaging Initiative, and specifically to determine which index of neurodegeneration was most frequently affected. The secondary objective was to determine the most frequently hypometabolic region in patients with a CSF AD signature (abnormal Aß1-42 and abnormal p-tau). We included the 372 subjects (85 normal subjects, 212 patients with mild cognitive impairment, and 75 patients with AD) with a CSF biomarker dosage (Aß1-42, t-tau, and p-tau) and brain FDG-PET. The relationship between FDG-PET metabolism (in five regions of interest (ROI) known to be damaged in AD) and CSF t-tau and p-tau levels was studied as a function of CSF Aß1-42 status. FDG-PET hypometabolism and CSF t-tau and p-tau levels were correlated only in patients with an abnormal CSF Aß1-42 level (t-tau: R2 = 0.044, p = 0.001; p-tau: R2 = 0.02, p = 0.03). In the latter patients, CSF p-tau was the most frequently (p = 0.0001) abnormal neurodegeneration marker (p-tau: 92.8%; FDG-PET: 56.5%; CSF t-tau: 59.1%). Within the five ROI of FDG PET, the angular gyrus metabolism (R2 = 0.149; p = 0.0001) was selected as the most tightly associated with CSF AD signature. The relation between CSF markers of neurodegeneration (p-tau and t-tau) and brain hypometabolism (in FDG-PET) is conditioned by presence of amyloid abnormality. This finding supports the current physiopathological model of AD. P-tau is the most frequently impaired biomarker. Using FDG PET angular gyrus hypometabolism is the most sensitive to CSF-biomarker-defined AD.

Quantization accuracy of short-duration respiratory-gated PET/CT acquisitions.

PURPOSE: PET/CT acquisitions are affected by physiological motion, which lowers the quantization accuracy. Respiratory-gated PET/CT methods require a long acquisition time, which may not be compatible with the clinical schedule. The objective of the present study was to assess the quantization accuracy of short-duration, respiratory-gated PET acquisitions and processing with the "CT-based" methodology developed in our laboratory. METHODS: Quantization accuracy was first assessed in a phantom study. A standard ("Ungated") PET/CT acquisition was followed by a 10-minute list-mode acquisition with simultaneous respiratory signal recording and a short breath-hold CT scan (BH-CT). These acquisitions were repeated 10 times. For the CT-based images, we reconstructed (i) 10 full-duration (FD-CT-based) volumes that took account of all events recorded in the position defined by BH-CT and (ii) 10 short-duration (SD-CT-based) volumes based on only 30 seconds of selected events. Using these volumes, we performed a bias-variance analysis to assess the effects of respiration-motion reduction and the counting statistics on the quantization accuracy. We also applied Ungated, FD- and SD-CT-based methods to 16 patients (21 pulmonary lesions) and measured the maximum standardized uptake (SUVmax) values. RESULTS: The bias values were 71%, 40% and 44% for Ungated, FD- and SD-CT-based images, respectively. In the clinical study, there was a statistically significant difference in SUVmax between Ungated images and both the CT-Based images (p < 0.02) but not between the FD-CT-Based and SD-CT-Based images (p = 0.42). CONCLUSION: Our findings demonstrated that the additional acquisition time required by the CT-based method can be reduced without altering quantitative accuracy.