Brain PET Imaging Research Articles

Early [(18)F]florbetaben and [(11)C]PiB PET images are a surrogate biomarker of neuronal injury in Alzheimer's disease.

[(18)F]FDG is a commonly used neuronal injury biomarker for early and differential diagnosis of dementia. Typically, the blood supply to the brain is closely coupled to glucose consumption. Early uptake of the Aβ tracer [(11)C]PiB on PET images is mainly determined by cerebral blood flow and shows a high correlation with [(18)F]FDG uptake. Uptake data for (18)F-labelled Aβ PET tracers are, however, scarce. We investigated the value of early PET images using the novel Aβ tracer [(18)F]FBB in the diagnosis of Alzhimers disease (AD). This retrospective analysis included 22 patients with MCI or dementia who underwent dual time-point PET imaging with either [(11)C]PiB (11 patients) or [(18)F]FBB (11 patients) in routine clinical practice. Images were acquired 1-9min after administration of both tracers and 40-70min and 90-110min after administration of [(11)C]PiB and [(18)F]FBB, respectively. The patients also underwent [(18)F]FDG brain PET imaging. PET data were analysed visually and semiquantitatively. Associations between early Aβ tracer uptake and dementia as well as brain atrophy were investigated. Regional visual scores of early Aβ tracer and [(18)F]FDG PET images were significantly correlated (Spearman's ρ = 0.780, P < 0.001). Global brain visual analysis revealed identical results between early Aβ tracer and [(18)F]FDG PET images. In a VOI-based analysis, the early Aβ tracer data correlated significantly with the [(18)F]FDG data (r = 0.779, P < 0.001), but there were no differences between [(18)F]FBB and [(11)C]PiB. Cortical SUVRs in regions typically affected in AD on early Aβ tracer and [(18)F]FDG PET images were correlated with MMSE scores (ρ = 0.458, P = 0.032, and ρ = 0.456, P = 0.033, respectively). A voxel-wise group-based search for areas with relatively higher tracer uptake on early Aβ tracer PET images compared with [(18)F]FDG PET images revealed a small cluster in the midbrain/pons; no significant clusters were found for the opposite comparison. Early [(18)F]FBB and [(11)C]PiB PET brain images are similar to [(18)F]FDG PET images in AD patients, and these tracers could potentially be used as biomarkers in place of [(18)F]FDG. Thus, Aβ tracer PET imaging has the potential to provide biomarker information on AD pathology and neuronal injury. The potential of this approach for supporting the diagnosis of AD needs to be confirmed in prospective studies in larger cohorts.

A Survey of PET Image Segmentation: Applications in Oncology, Cardiology and Neurology

Positron Emission Tomography, which is a functional imaging technique, measures in three-dimension the bio-distribution of a radiotracer in a specific organ or tissue. Thanks to tracer characteristics, the PET imaging was successfully experimented into several applications in oncology, cardiology and neurology for clinical and research trials. The segmentation of PET image is a mandatory step in all PET applications since it allows to relay imaged tracer uptake within a region of interest to its underlying biology. However, manual segmentation was limited by its time consuming, labor intensive and its high intra- and inter-operator variability. Therefore, several automated PET image segmentation methods were developed. In this paper, we presented the most relevant methods in the literature including thresholding-based methods of static PET images, deformable models for cardiac PET studies and mono and multi-modal segmentation methods for brain PET images. Keywords: Cardiology, deformable models, multi-modal segmentation, neurology, oncology, PET image, thresholding-based segmentation.

A perspective on the future role of brain pet imaging in exercise science

Positron Emission Tomography (PET) bears a unique potential for examining the effects of physical exercise (acute or chronic) within the central nervous system in vivo, including cerebral metabolism, neuroreceptor occupancy, and neurotransmission. However, application of Neuro-PET in human exercise science is as yet surprisingly sparse. To date the field has been dominated by non-invasive neuroelectrical techniques (EEG, MEG) and structural/functional magnetic resonance imaging (sMRI/fMRI). Despite PET having certain inherent disadvantages, in particular radiation exposure and high costs limiting applicability at large scale, certain research questions in human exercise science can exclusively be addressed with PET: The “metabolic trapping” properties of 18F-FDG PET as the most commonly used PET-tracer allow examining the neuronal mechanisms underlying various forms of acute exercise in a rather unconstrained manner, i.e. under realistic training scenarios outside the scanner environment. Beyond acute effects, 18F-FDG PET measurements under resting conditions have a strong prospective for unraveling the influence of regular physical activity on neuronal integrity and potentially neuroprotective mechanisms in vivo, which is of special interest for aging and dementia research. Quantification of cerebral glucose metabolism may allow determining the metabolic effects of exercise interventions in the entire human brain and relating the regional cerebral rate of glucose metabolism (rCMRglc) with behavioral, neuropsychological, and physiological measures. Apart from FDG-PET, particularly interesting applications comprise PET ligand studies that focus on dopaminergic and opioidergic neurotransmission, both key transmitter systems for exercise-related psychophysiological effects, including mood changes, reward processing, antinociception, and in its most extreme form ‘exercise dependence’. PET ligand displacement approaches even allow quantifying specific endogenous neurotransmitter release under acute exercise interventions, to which modern PET/MR hybrid technology will be additionally fruitful. Experimental studies exploiting the unprecedented multimodal imaging capacities of PET/MR in human exercise sciences are as yet pending.

(18F)FDG-PET brain imaging during the micturition cycle in rats detects regions involved in bladder afferent signalling

BackgroundThis feasibility study established an experimental protocol to evaluate brain activation patterns using fluorodeoxyglucose positron emission tomography ((18F)FDG-PET) during volume-induced voiding and isovolumetric bladder contractions in rats.MethodsFemale Sprague-Dawley rats were anaesthetized with urethane and underwent either volume-induced voiding cystometry or isovolumetric cystometry and simultaneous functional PET brain imaging after injection of (18F)FDG in the tail vein. Brain glucose metabolism in both groups was compared to their respective control conditions (empty bladder). Relative glucose metabolism images were anatomically standardized to Paxinos space and analysed voxel-wise using Statistical Parametric Mapping 12 (SPM12).ResultsDuring volume-induced voiding, glucose hypermetabolism was observed in the insular cortex while uptake was decreased in a cerebellar cluster and the dorsal midbrain. Relative glucose metabolism during isovolumetric bladder contractions increased in the insular and cingulate cortices and decreased in the cerebellum.ConclusionsOur findings demonstrate that volume-induced voiding as well as isovolumetric bladder contractions in rats provokes changes in brain metabolism, including activation of the insular and cingulate cortices, which is consistent with their role in the mapping of bladder afferent activity. These findings are in line with human studies. Our results provide a basis for further research into the brain control of the lower urinary tract in small laboratory animals.

Striatal and Cortical β-Amyloidopathy and Cognition in Parkinson's Disease.

Although most previous cognitive studies of β-amyloidopathy in PD focused on cortical plaque deposition, recent postmortem studies point to an important role of striatal β-amyloid plaque deposition. The aim of this study was to investigate the relative contributions of striatal and cortical β-amyloidopathy to cognitive impairment in PD. Patients with PD (n = 62; age, 68.9 ± 6.4 years; H & Y stage: 2.7 ± 0.5; MoCA score: 25.2 ± 3.0) underwent [(11) C]Pittsburgh compound B β-amyloid, [(11) C]dihydrotetrabenazine monoaminergic, and [(11) C]methyl-4-piperidinyl propionate acetylcholinesterase brain PET imaging and neuropsychological assessment. [(11) C]Pittsburgh compound B β-amyloid data from young to middle-aged healthy subjects were used to define elevated [(11) C]Pittsburgh compound B binding in patients. Elevated cortical and striatal β-amyloid deposition were present in 37% and 16%, respectively, of this predominantly nondemented cohort of patients with PD. Increased striatal β-amyloid deposition occurred in half of all subjects with increased cortical β-amyloid deposition. In contrast, increased striatal β-amyloid deposition did not occur in the absence of increased cortical β-amyloid deposition. Analysis of covariance using global composite cognitive z scores as the outcome parameter showed significant regressor effects for combined striatal and cortical β-amyloidopathy (F = 4.18; P = 0.02) after adjusting for covariate effects of cortical cholinergic activity (F = 5.67; P = 0.02), caudate nucleus monoaminergic binding, duration of disease, and age (total model: F = 3.55; P = 0.0048). Post-hoc analysis showed significantly lower cognitive z score for combined striatal and cortical β-amyloidopathy, compared to cortical-only β-amyloidopathy and non-β-amyloidopathy subgroups. The combined presence of striatal and cortical β-amyloidopathy is associated with greater cognitive impairment than cortical β-amyloidopathy alone in PD.

Detecting and estimating head motion in brain PET acquisitions using raw time-of-flight PET data

Head motion during brain PET imaging is not uncommon and can negatively affect image quality. Motion correction techniques typically either use hardware to prospectively measure head motion, or they divide the acquisition into short fixed-frames and then align and combine these to produce a motion free image. The aim of this work was to retrospectively detect when motion occurred in PET data without the use of motion detection hardware, and then align the frames defined by these motion occurrences. We describe two methods that use either principal component analysis or the motion induced spatial displacements over time to detect motion in raw time-of-flight PET data. The points in time of motion then define the temporal boundaries of frames which are reconstructed without attenuation correction, aligned and combined. Phantom and [18F]-Fallypride patient acquisitions were used to validate and evaluate these approaches, which were compared with motion estimation using 60 s fixed-frames. Both methods identified all motion occurrences in phantom data, and unlike the fixed-frame approach did not exhibit intra-frame motion. With patient acquisitions, images corrected with the motion detection methods increased the average image sharpness by the same amount as the fixed-frame approach, but reduced the number of reconstructions and registrations by a factor of 3.4 on average. Detecting head motion in raw PET data alone is possible, allowing retrospective motion estimation of any listmode brain PET acquisition without additional hardware, subsequently decreasing data processing and potentially reducing intra-frame motion.

18F-FDG PET Improves Diagnosis in Patients with Focal-Onset Dementias.

Alzheimer disease is the cause of up to one-third of cases of primary progressive aphasia or corticobasal syndrome. The primary objective of this study was to determine the accuracy of 18F-FDG PET metabolic imaging for the detection of Alzheimer disease in patients with primary progressive aphasia or corticobasal syndrome. A cohort of patients (n=94), including those with an expert clinical diagnosis of logopenic (n=19), nonfluent (n=16), or semantic (n=13) variants of primary progressive aphasia, corticobasal syndrome (n=14), or Alzheimer disease (n=24), underwent 18F-FDG metabolic and 11C-labeled Pittsburgh compound B (11C-PiB) amyloid PET brain imaging. 18F-FDG PET scans interpreted with Neurostat and 3D-SSP displays were classified as revealing Alzheimer disease or "other" by interpreters who were unaware of the clinical assessments and 11C-PiB PET results. 11C-PiB PET imaging was considered to be the diagnostic reference standard, with a threshold standardized uptake value ratio of 1.5 being indicative of Alzheimer disease pathology. To address possible bias from subgroup selection for the Alzheimer disease binary classifier, we calculated both conventional and balanced accuracies. Diagnoses of Alzheimer disease based on 18F-FDG PET resulted in 84% accuracy (both conventional and balanced). In comparison, diagnoses based on clinical assessments resulted in 65% conventional accuracy and 67% balanced accuracy. Brain 18F-FDG PET scans interpreted with Neurostat and 3D-SSP displays accurately detected Alzheimer disease in patients with primary progressive aphasia or corticobasal syndrome as focal-onset dementias. In such diagnostically challenging cohorts, (18)F-FDG PET imaging can provide more accurate diagnoses, enabling more appropriate therapy.

Brain PET imaging optimization with time of flight and point spread function modelling

PurposeTo assess the influence of reconstruction algorithms and parameters on the PET image quality of brain phantoms in order to optimize reconstruction for clinical PET brain studies in a new generation PET/CT. MethodsThe 3D Hoffman phantom that simulates 18F-fluorodeoxyglucose (FDG) distribution was imaged in a Siemens Biograph mCT TrueV PET/CT with Time of Flight (TOF) and Point Spread Function (PSF) modelling. Contrast-to-Noise Ratio (CNR), contrast and noise were studied for different reconstruction models: OSEM, OSEM + TOF, OSEM + PSF and OSEM + PSF + TOF.The 2D multi-compartment Hoffman phantom was filled to simulate 4 different tracers' spatial distribution: FDG, 11C-flumazenil (FMZ), 11C-Methionine (MET) and 6-18F-fluoro-l-dopa (FDOPA). The best algorithm for each tracer was selected by visual inspection. The maximization of CNR determined the optimal parameters for each reconstruction. ResultsIn the 3D Hoffman phantom, both noise and contrast increased with increasing number of iterations and decreased with increasing FWHM. OSEM + PSF + TOF reconstruction was generally superior to other reconstruction models. Visual analysis of the 2D Hoffman brain phantom suggested that OSEM + PSF + TOF is the optimum algorithm for tracers with focal uptake, such as MET or FDOPA, and OSEM + TOF for tracers with diffuse cortical uptake (i.e. FDG and FMZ). Optimization of CNR demonstrated that OSEM + TOF reconstruction must be performed with 2 iterations and a filter FWHM of 3 mm, and OSEM + PSF + TOF reconstruction with 4 iterations and 1 mm FWHM filter. ConclusionsOptimization of reconstruction algorithm and parameters has been performed to take particular advantage of the last generation PET scanner, recommending specific settings for different brain PET radiotracers.

FDG and 82Rb PET/MRI Features of Brain Metastasis of Breast Cancer

A 64-year-old woman with stage IV breast cancer underwent an FDG and Rb PET brain studies. The PET brain images were fused with MRI brain T1 post-contrast images. The known enhancing left superoposterior frontal brain metastasis is positive on both FDG Rb PET/MRI images. The Rb PET/MRI showed better target-to-noise ratio, but showed nonspecific uptake in the superior sagittal sinus.

Synthesis, characterization, and preclinical validation of a PET radiopharmaceutical for interrogating Aβ (β-amyloid) plaques in Alzheimer's disease.

BackgroundPET radiopharmaceuticals capable of imaging β-amyloid (Aβ) plaque burden in the brain could offer highly valuable diagnostic tools for clinical studies of Alzheimer’s disease. To further supplement existing armamentarium of FDA-approved agents as well as those under development, and to correlate multiphoton-imaging data reported earlier, herein, we describe preclinical validation of a PET tracer.MethodsA novel PET radiopharmaceutical (18F-7B) was synthesized and characterized. To assess its affinity for Aβ, binding assays with Aβ1-42 fibrils, Alzheimer’s disease (AD) homogenates, and autoradiography studies and their IHC correlations were performed. For assessing its overall pharmacokinetic profiles in general and its ability to cross the blood-brain barrier (BBB) in particular, biodistribution studies in normal mice were performed. Finally, for evaluating potential for 18F-7B to serve as a targeted Aβ probe, the microPET/CT imaging was performed in age-matched amyloid precursor protein/presenilin-1 (APP/PS1) mice and wild-type (WT) counterparts.ResultsThe radiotracer 18F-7B shows saturable binding to autopsy-confirmed AD homogenates (Kd = 17.7 nM) and Aβ1-42 fibrils (Kd = 61 nM). Preliminary autoradiography studies show binding of 18F-7B to cortical Aβ plaques in autopsy-confirmed AD tissue sections, inhibition of that binding by unlabeled counterpart 7A-indicating specificity, and a good correlation of tracer binding with Aβ immunostaining. The agent indicates high initial penetration into brains (7.23 ± 0.47%ID/g; 5 min) of normal mice, thus indicating a 5-min/120-min brain uptake clearance ratio of 4.7, a benchmark value (>4) consistent with the ability of agents to traverse the BBB to enable PET brain imaging. Additionally, 18F-7B demonstrates the presence of parental species in human serum. Preliminary microPET/CT imaging demonstrates significantly higher retention of 18F-7B in brains of transgenic mice compared with their WT counterparts, consistent with expected binding of the radiotracer to Aβ plaques, present in APP/PS1 mice, compared with their age-matched WT counterparts lacking those Aβ aggregates.ConclusionsThese data offer a platform scaffold conducive to further optimization for developing new PET tracers to study Aβ pathophysiology in vitro and in vivo.

Impact of atlas-CT-based bone anatomy compensation on MR-based attenuation correction for brain PET imaging in a time-of-flight PET/MRI system: A direct comparison to a patient-CT-based approach.

An atlas-CT-based bone-anatomy compensation for MR-based attenuation correction (MRAC) in brain PET/MRI imaging is a current standard. However, the impact of an anatomical difference has not been clinically evaluated. Thus, we aim to evaluate the impact of the anatomical dissimilarity on MRAC. Whole-body FDG-PET/CT followed by PET/MRI were performed for twelve patients in an integrated TOF PET/MRI system. The MRAC utilized an atlas-CT (MRAC-atlas) as well as a patient-specific-CT (MRAC patient) to produce AC maps (pseudo-CT). Instead of using atlas-CT, the MRAC-patient approach derived pseudo-CT from patient-specific-CT aligned to MR. For quantitative evaluation, CTAC was considered as gold standard for AC, and PET mean activity concentration values were measured and compared in eight 10 ml volumes-of-interest (VOI). PET activity concentration with MRAC, compared to CTAC, were systematically underestimated on average by 0.63±0.34 kBq/ml (4.0±2.2%) and 0.22±0.21 kBq/ml (1.4±1.5%) for the MRAC-atlas and the MRAC-patient, respectively: using the MRAC atlas, the error was increased to 0.41±0.25 kBq/ml (2.6±1.8%) on average (p≈0). However, the error increase was patient-dependent (highest: 5.7% vs. lowest: 0.3%) and VOI dependent (highest 3.1% vs. lowest: 1.9%). For the first time, the atlas-CT based MRAC was compared to the patient-specific-CT-based MRAC for brain PET imaging in an integrated TOF PET/MRI system. Overall, the MRAC-atlas achieves quantification accuracy similar to CTAC with a small but measurable difference of 5% in values, which is 2.6% higher than the error of the MRAC-patient.

Correlation between extratemporal hypometabolism and the outcome of temporal lobectomy in patients with temporal lobe epilepsy

Objective To explore the correlation between extratemporal hypometabolism on preoperative 18F-FDG PET imaging and the outcome after temporal lobectomy in temporal lobe epilepsy (TLE) patients. Methods A total of 96 patients with intractable TLE who underwent temporal lobectomy were recruited. The outcome was evaluated according to International League Against Epilepsy (ILAE) 2001 outcome classification (OC) criteria: OC 1-3 was considered as good outcome and OC4-6 as poor outcome. The follow-up period was more than 2 years. The 18F-FDG PET brain images were retrospectively analyzed. The preoperative extratemporal cortical hypometabolism and extratemporal subcortical hypometabolism occurred in basal ganglia and thalamus were taken as independent exposure factors of poor outcome and the odds ratios (OR) were calculated respectively. Results Thirteen of 96 cases had poor outcome. Extratemporal cortical hypometabolism was found in 12 of 83(14.5%) cases with good outcome and in 11 of 13 cases with poor outcome. Extratemporal subcortical hypometabolism was found in 25 of 83(30.1%) cases with good outcome and in 10 of 13 cases with poor outcome. The occurrence of extratemporal hypometabolism was significantly higher in poor outcome group than that in good surgical outcome group (cortical: χ2=26.63; subcortical: χ2=8.70; both P<0.05). The OR of extratemporal cortical hypometabolism was 32.54, with 95% CI of 6.40-165.44, and that of extratemporal subcortical hypometabolism was 7.73, with 95% CI of 1.96-30.52. Conclusion Extratemporal cortical hypometabolism and subcortical hypometabolism in TLE patients are associated with poor outcome of temporal lobectomy in TLE patients. Key words: Epilepsy, temporal lobe; Anterior temporal lobectomy; Metabolism; Treatment outcome

Anatomy-guided brain PET imaging incorporating a joint prior model

We proposed a maximum a posterior (MAP) framework for incorporating information from co-registered anatomical images into PET image reconstruction through a novel anato-functional joint prior. The characteristic of the utilized hyperbolic potential function is determinate by the voxel intensity differences within the anatomical image, while the penalization is computed based on voxel intensity differences in reconstructed PET images. Using realistic simulated 18FDG PET scan data, we optimized the performance of the proposed MAP reconstruction with the joint prior (JP-MAP) and compared its performance with conventional 3D MLEM and 3D MAP reconstructions. The proposed JP-MAP reconstruction algorithm resulted in quantitatively enhanced reconstructed images, as demonstrated in extensive FDG PET simulation study. The proposed method was also tested on a 20 min Florbetapir patient study performed on the high-resolution research tomograph. It was shown to outperform conventional methods in visual as well as quantitative accuracy assessment (in terms of regional noise versus activity value performance). The JP-MAP method was also compared with another MR-guided MAP reconstruction method, utilizing the Bowsher prior and was seen to result in some quantitative enhancements, especially in the case of MR-PET mis-registrations, and a definitive improvement in computational performance.

The Impact of Accelerated HF-rTMS on the Subgenual Anterior Cingulate Cortex in Refractory Unipolar Major Depression: Insights From 18FDG PET Brain Imaging.

Although one of the most frequent diagnosed mental illnesses worldwide, it appears to be challenging to successfully treat major depressive disorder (MDD). Although the phenomenon of treatment-resistant depression (TRD) still remains unclear, the subgenual anterior cingulate cortex (sgACC) has been put forward as a possible neurobiological marker to evaluate clinical effects of a variety of antidepressant treatments, including repetitive transcranial magnetic stimulation (rTMS). Accelerated high-frequency (HF)-rTMS may have the potential to rapidly result in beneficial clinical outcomes in TRD. No studies yet examined the clinical effects of such accelerated stimulation treatment paradigms on sgACC regional glucose metabolism (CMRglc), nor the predictive value of the latter for clinical outcome. First, we investigated the predictive value of baseline sgACC metabolic activity for clinical outcome. Second, we hypothesized that in clinical responders only accelerated HF-rTMS treatment would result in significant metabolic decreases. We recruited right-handed antidepressant-free unipolar melancholic TRD patients to participate in a two-week randomized sham-controlled crossover HF-rTMS treatment study. Stimulation was applied to the left dorsolateral prefrontal cortex (DLPFC). Fifteen patients underwent 18FDG PET (CMRglc) at baseline (T0), after the first week (T1) of accelerated HF-rTMS and at the end of the treatment after the second week (T2). Higher baseline sgACC metabolic activity may indicate beneficial clinical outcome to this kind of accelerated HF-rTMS treatment. Moreover, clinical response resulted in a significant decrease in sgACC CMRglc. Non-response did not affect sgACC CMRglc. Our results add to the sgACC as a specific neurobiological marker for anti-depressive response in accelerated HF-rTMS treatment paradigms. Such protocols may not only have the ability to result in fast clinical responses but they may also have potential to acutely modulate a dysfunctional sgACC.

Qualitative and Quantitative Evaluation of Blob-Based Time-of-Flight PET Image Reconstruction in Hybrid Brain PET/MR Imaging.

PurposeMany neurological diseases affect small structures in the brain and, as such, reliable visual evaluation and accurate quantification are required. Recent technological developments made the clinical use of hybrid positron emission tomography/magnetic resonance (PET/MR) systems possible, providing both functional and anatomical information in a single imaging session. Nevertheless, there is a trade-off between spatial resolution and image quality (contrast and noise), which is dictated mainly by the chosen acquisition and reconstruction protocols. Image reconstruction algorithms using spherical symmetric basis functions (blobs) for image representation have a number of additional parameters that impact both the qualitative and quantitative image characteristics. Hence, a detailed investigation of the blob-based reconstruction characteristics using different parameters is needed to achieve optimal reconstruction results.ProceduresThis work evaluated the impact of a range of blob parameters on image quality and quantitative accuracy of brain PET images acquired on the Ingenuity Time-of-Flight (TOF) PET/MR system. Two different phantoms were used to simulate brain imaging applications. Image contrast and noise characteristics were assessed using an image quality phantom. Quantitative performance in a clinical setting was investigated using the Hoffman 3D brain phantom at various count levels. Furthermore, the visual quality of four clinical studies was scored blindly by two experienced physicians to qualitatively evaluate the influence of different reconstruction protocols, hereby providing indications on parameters producing the best image quality.ResultsQuantitative evaluation using the image quality phantom showed that larger basis function radii result in lower contrast recovery (∼2 %) and lower variance levels (∼15 %). The brain phantom and clinical studies confirmed these observations since lower contrast was seen between anatomical structures. High and low count statistics gave comparable values. The qualitative evaluation of the clinical studies, based on the assessment performed by the physicians, showed a preference towards lower image variance levels with a slightly lower contrast, favoring higher radii and four iterations.ConclusionThis study systematically evaluated a number of basis function parameters and their quantitative and qualitative effect within PET image reconstruction in the context of brain imaging. A range of blob parameters can minimize error and provided optimal image quality, where the anatomical structures could be recognized but the exact delineation of these structures is simplified in scans with lower image variance levels and thus, higher radii should be preferred. With the optimization of blob parameters, the reconstructed images were found to be qualitatively improved (optimum parameters {d = 2.0375, alpha = 10.4101, radius = 3.9451}) as assessed by the physicians compared to the current clinical protocol. However, this qualitative improvement is task specific, depending on the desired image characteristics to be extracted. Finally, this work could be used as a guide for application-specific optimal parameter selection.Electronic supplementary materialThe online version of this article (doi:10.1007/s11307-015-0824-x) contains supplementary material, which is available to authorized users.

Feasibility of simultaneous whole-brain imaging on an integrated PET-MRI system using an enhanced 2-point Dixon attenuation correction method.

Purpose: To evaluate a potential approach for improved attenuation correction (AC) of PET in simultaneous PET and MRI brain imaging, a straightforward approach that adds bone information missing on Dixon AC was explored.Methods: Bone information derived from individual T1-weighted MRI data using segmentation tools in SPM8, were added to the standard Dixon AC map. Percent relative difference between PET reconstructed with Dixon+bone and with Dixon AC maps were compared across brain regions of 13 oncology patients. The clinical potential of the improved Dixon AC was investigated by comparing relative perfusion (rCBF) measured with arterial spin labeling to relative glucose uptake (rPETdxbone) measured simultaneously with 18F-flurodexoyglucose in several regions across the brain.Results: A gradual increase in PET signal from center to the edge of the brain was observed in PET reconstructed with Dixon+bone. A 5–20% reduction in regional PET signals were observed in data corrected with standard Dixon AC maps. These regional underestimations of PET were either reduced or removed when Dixon+bone AC was applied. The mean relative correlation coefficient between rCBF and rPETdxbone was r = 0.53 (p < 0.001). Marked regional variations in rCBF-to-rPET correlation were observed, with the highest associations in the caudate and cingulate and the lowest in limbic structures. All findings were well matched to observations from previous studies conducted with PET data reconstructed with computed tomography derived AC maps.Conclusion: Adding bone information derived from T1-weighted MRI to Dixon AC maps can improve underestimation of PET activity in hybrid PET-MRI neuroimaging.

Early Detection and Current Therapies for Alzheimer’s Disease

With life expectancy increasing across the world, the number of elderly people at risk of developing dementia is growing rapidly. The prevalence of dementia rises steeply with age which remains the number one risk factor, doubling every five years from the age of 60. Therefore, more than one-third of individuals over the age of 80 years are likely to develop dementia. Alzheimer’s disease (AD) remains the most common cause of dementia in all age groups. AD is a slowly progressive neurodegenerative brain disorder that, according to several imaging and neuropsychological studies, has the prodromal stage that can be traced back to 15-20 years prior to symptom presentation. AD is characterized by the presence of amyloid plaques and neurofibrillary tangles together with the loss of cortical neurons and synapses. Post mortem studies suggest that temporal lobes are the first brain regions that are affected. The cognitive deficits that are associated with AD become evident and gradually worsen in later years. The combination of aging population and the promise of possible modifications in therapies in the near future has made the characterization of the early stages of AD a topic of major research interest. The transitional stage between normal memory and dementia is called Mild Cognitive Impairment (MCI). Although it has been difficult to develop robust and applicable criteria for MCI, it is generally agreed that it is a pre-dementia state that in the majority of cases evolves into a full-blown dementia within five years from diagnosis. In this stage, there are also persistent memory lapses observed. Research has suggested that early detection and treatment of AD provides symptomatic improvement and better quality of life, though it does not address the underlying pathology or prolonged survival. For many patients, the quality of life is important since the disease progresses slowly. For several years, the brain PET imaging has been used to diagnose AD by demonstrating decreased metabolism in the temporal and parietal regions. Given the importance of early detection, several tracers, such as Pittsburgh compound B (PIB), Florbetapir, and Flutemetamol have been developed to detect the amyloid deposits in the brain, and along with the CSF studies of measuring the concentration of beta amyloid, have significantly improved the accuracy of AD diagnosis. The majority of the above-mentioned measures are mainly utilized in research centers. Other measures include genetic testing with APO E, PS1, PS2, and APP genes. Given the lack of effective treatments for AD, routine genetic testing is not recommended. The current standard of care in clinical evaluation of patients with cognitive disorders includes a comprehensive interview with the family and the patient, a full neuropsychological evaluation, brain MRI, and blood tests including thyroid function, B12, folic acid, vitamin D, and rapid plasma reagin (RPR) to rule out other reversible causes of dementia. Currently, there are two classes of drugs that are used in clinical practice; one class is the cholinesterase inhibitors donepezil, rivastigmine, and galantamine with some minor differences, but similar effects. The mechanism of action of these drugs is by inhibiting the enzyme cholinesterase; they increase the availability of acetylcholine in the synapse. The other class of drug is the N-Methyl D-Aspartate (NMDA) receptor antagonist memantine. The mechanism of action of this drug is thought to be inhibiting calcium influx and hyperexcitability and reducing cell death. In the present state of research, we are testing several classes of promising drugs that are in various stages of development. These include beta-site APP Cleaving Enzyme (BACE) inhibitors, passive anti-amyloid antibody infusion, nicotinic and muscarinic agonists and several serotonin agonists and antagonists that can be offered with and without the current marketed drugs. Co r r e s pondence

Analysis of Brain PET Images with MR Images

Analysis of Brain PET Images with MR Images

Prediction of standard-dose brain PET image by using MRI and low-dose brain [ 18 F]FDG PET images: Prediction of standard-dose brain PET image

Prediction of standard-dose brain PET image by using MRI and low-dose brain [ 18 F]FDG PET images: Prediction of standard-dose brain PET image

Familial risk for major depression is associated with lower striatal 5-HT₄ receptor binding.

Background:The 5-HT4 receptor provides a novel potential target for antidepressant treatment. No studies exist to elucidate the 5-HT4 receptor’s in vivo distribution in the depressed state or in populations that may display trait markers for major depression disorder (MDD). The aim of this study was to determine whether familial risk for MDD is associated with cerebral 5-HT4 receptor binding as measured with [11C]SB207145 brain PET imaging. Familial risk is the most potent risk factor of MDD.Methods:We studied 57 healthy individuals (mean age 36 yrs, range 20–86; 21 women), 26 of which had first-degree relatives treated for MDD.Results:We found that having a family history of MDD was associated with lower striatal 5-HT4 receptor binding (p = 0.038; in individuals below 40 years, p = 0.013). Further, we found evidence for a “risk-dose effect” on 5-HT4 receptor binding, since the number of first-degree relatives with a history of MDD binding correlated negatively with 5-HT4 receptor binding in both the striatum (p = 0.001) and limbic regions (p = 0.012).Conclusions:Our data suggest that the 5-HT4 receptor is involved in the neurobiological mechanism underlying familial risk for depression, and that lower striatal 5-HT4 receptor binding is associated with increased risk for developing MDD. The finding is intriguing considering that the 5-HT4 receptor has been suggested to be an effective target for antidepressant treatment.