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[18F]MK-6240 meningeal/extracerebral off-target binding may impact tau quantification. We examined the kinetics and longitudinal changes of extracerebral and reference regions. [18F]MK-6240 PET was performed in 24 cognitively-normal and eight cognitively-impaired subjects, with arterial samples in 13 subjects. Follow-up scans at 6.1 ± 0.5 (n = 25) and 13.3 ± 0.9 (n = 16) months were acquired. Extracerebral and reference region (cerebellar gray matter (CerGM)-based, cerebral white matter (WM), pons) uptake were evaluated using standardized uptake values (SUV90-110), spectral analysis, and distribution volume. Longitudinal changes in SUV90-110 were examined. The impact of reference region on target region outcomes, partial volume correction (PVC) and regional erosion were evaluated. Eroded WM and pons showed lower variability, lower extracerebral contamination, and lower longitudinal changes than CerGM-based regions. CerGM-based regions resulted larger cross-sectional effect sizes for group differentiation. Extracerebral signal was high in 50% of subjects and exhibited irreversible kinetics and nonsignificant longitudinal changes over one-year but was highly variable at subject-level. PVC resulted in higher variability in reference region uptake and longitudinal changes. Our results suggest that eroded CerGM may be preferred for cross-sectional, whilst eroded WM or pons may be preferred for longitudinal [18F]MK-6240 studies. For CerGM, erosion was necessary (preferred over PVC) to address the heterogenous nature of extracerebral signal.

The brainstem is among the first regions to accumulate Alzheimer’s disease (AD)-related hyperphosphorylated tau pathology during aging. We aimed to examine associations between brainstem volume and neocortical amyloid-β or tau pathology in 271 middle-aged clinically normal individuals of the Framingham Heart Study who underwent MRI and PET imaging. Lower volume of the medulla, pons, or midbrain was associated with greater neocortical amyloid burden. No associations were detected between brainstem volumes and tau deposition. Our results support the hypothesis that lower brainstem volumes are associated with initial AD-related processes and may signal preclinical AD pathology.

6-(fluoro-18F)-3-(1H-pyrrolo[2,3-c]pyridin-1-yl)isoquinolin-5-amine ([18F]MK6240) has high affinity and selectivity for hyperphosphorylated tau and readily crosses the blood-brain barrier. This study investigated whether the early phase of [18F]MK6240 can be used to provide a surrogate index of cerebral perfusion. Methods: Forty-nine subjects who were cognitively normal (CN), had mild cognitive impairment (MCI), or had Alzheimer's disease (AD) underwent paired dynamic [18F]MK6240 and [11C]Pittsburgh compound B (PiB) PET, as well as structural MRI to obtain anatomic information. Arterial blood samples were collected in a subset of 24 subjects for [18F]MK6240 scans to derive metabolite-corrected arterial input functions. Regional time-activity curves were extracted using atlases available in the Montreal Neurologic Institute template space and using FreeSurfer. The early phase of brain time-activity curves was analyzed using a 1-tissue-compartment model to obtain a robust estimate of the rate of transfer from plasma to brain tissue, K 1 (mL⋅cm-3⋅min-1), and the simplified reference tissue model 2 was investigated for noninvasive estimation of the relative delivery rate, R 1 (unitless). A head-to-head comparison with R 1 derived from [11C]PiB scans was performed. Grouped differences in R 1 were evaluated among CN, MCI, and AD subjects. Results: Regional K 1 values suggested a relatively high extraction fraction. R 1 estimated noninvasively from simplified reference tissue model 2 agreed well with R 1 calculated indirectly from the blood-based compartment modeling (r = 0.99; mean difference, 0.024 ± 0.027), suggesting that robust estimates were obtained. R 1 measurements obtained with [18F]MK6240 correlated strongly and overall agreed well with those obtained from [11C]PiB (r = 0.93; mean difference, -0.001 ± 0.068). Statistically significant differences were observed in regional R 1 measurements among CN, MCI, and AD subjects, notably in the temporal and parietal cortices. Conclusion: Our results provide evidence that the early phase of [18F]MK6240 images may be used to derive a useful index of cerebral perfusion. The early and late phases of a [18F]MK6240 dynamic acquisition may thus offer complementary information about the pathophysiologic mechanisms of the disease.

Introduction Impaired self-awareness of memory function, a.k.a. anosognosia, is a common symptom in Alzheimer’s disease (AD); however, its pathological correlates remain unclear. Here, we investigated the impact of amyloid and tau on memory self-awareness. Methods Two hundred thirty-six clinically normal (N) and 102 impaired (I) participants from the ADNI cohort were included. Amyloid (global) and tau burden (in entorhinal and inferior temporal cortices) were assessed using positron emission tomography (PET). Self-awareness of memory was assessed using discrepancy indexes of subjective participant-informant ratings, as well as participant-objective scores of memory performance. Subjective and objective values were derived from the Everyday Cognition memory questionnaire and Logical Memory (delayed recall). Results Lower awareness (both methods) of memory function was associated with higher levels of pathology in the I group as compared to N. There was a significant effect of tauopathy, but not amyloidosis, on individual complaint, such that higher levels of tau associated with lower awareness. Discussion Impaired self-awareness appears progressively in the evolution of the disease related to AD biomarkers. Discordant subjective and objective measures may be important for clinical consideration.

Objective. Positron emission tomography (PET) imaging of tau deposition using [18F]-MK6240 often involves long acquisitions in older subjects, many of whom exhibit dementia symptoms. The resulting unavoidable head motion can greatly degrade image quality. Motion increases the variability of PET quantitation for longitudinal studies across subjects, resulting in larger sample sizes in clinical trials of Alzheimer’s disease (AD) treatment. Approach. After using an ultra-short frame-by-frame motion detection method based on the list-mode data, we applied an event-by-event list-mode reconstruction to generate the motion-corrected images from 139 scans acquired in 65 subjects. This approach was initially validated in two phantoms experiments against optical tracking data. We developed a motion metric based on the average voxel displacement in the brain to quantify the level of motion in each scan and consequently evaluate the effect of motion correction on images from studies with substantial motion. We estimated the rate of tau accumulation in longitudinal studies (51 subjects) by calculating the difference in the ratio of standard uptake values in key brain regions for AD. We compared the regions’ standard deviations across subjects from motion and non-motion-corrected images. Main results. Individually, 14% of the scans exhibited notable motion quantified by the proposed motion metric, affecting 48% of the longitudinal datasets with three time points and 25% of all subjects. Motion correction decreased the blurring in images from scans with notable motion and improved the accuracy in quantitative measures. Motion correction reduced the standard deviation of the rate of tau accumulation by −49%, −24%, −18%, and −16% in the entorhinal, inferior temporal, precuneus, and amygdala regions, respectively. Significance. The list-mode-based motion correction method is capable of correcting both fast and slow motion during brain PET scans. It leads to improved brain PET quantitation, which is crucial for imaging AD.

OBJECTIVE: Women have a higher lifetime risk of AD than men. Among cognitively normal (CN) older adults, women exhibit elevated tau positron emission tomography (PET) signal compared with men. We explored whether menopause exacerbates sex differences in tau deposition in middle-aged adults.METHODS: 328 CN participants from the Framingham Study (mean age=57yrs(±10yrs), 161 women, of whom, 104 were post-menopausal) underwent tau and β-amyloid (Aβ)-PET neuroimaging. We examined global Aβ-PET, and tau-PET signal in five regions identified a priori as demonstrating significant sex differences in older adults (in temporal, inferior parietal, middle frontal, and lateral occipital regions). We examined sex and menopause status-related differences in each region-of-interest, using linear regressions, as well as interactions with Aβ and APOEε4 genotype.RESULTS: Women exhibited higher tau-PET signal (pINTERPRETATION: Clear divergence in tauopathy between the sexes are apparent approximately 20 years earlier than previously reported. Menopause status moderated sex differences in Aβ and tau-PET burden, with tau first appearing post-menopause. Sex and menopause differences consistently appeared in middle frontal and parieto-occipital regions but were not moderated by Aβ burden or APOEε4, suggesting that menopause-related tau vulnerability may be independent of AD-related pathways. This article is protected by copyright. All rights reserved.

In an attempt to explain experimental evidence of chaotic oscillations in blood cell population, A. Lasota suggested in 1977 a discrete-time one-dimensional model for the production of blood cells, and he showed that this equation allows to model the behavior of blood cell population in many clinical cases. Our main aim in this note is to carry out a detailed study of Lasota's equation, in particular revisiting the results in the original paper and showing new interesting phenomena. The considered equation is also suitable to model the dynamics of populations with discrete reproductive seasons, adult survivorship, overcompensating density dependence, and Allee effects. In this context, our results show the rich dynamics of this type of models and point out the subtle interplay between adult survivorship rates and strength of density dependence (including Allee effects).

Positron emission tomography (PET) plays an increasingly important role in research and clinical applications, catalysed by remarkable technical advances and a growing appreciation of the need for reliable, sensitive biomarkers of human function in health and disease. Over the last 30 years, a large amount of the physics and engineering effort in PET has been motivated by the dominant clinical application during that period, oncology. This has led to important developments such as PET/CT, whole-body PET, 3D PET, accelerated statistical image reconstruction, and time-of-flight PET. Despite impressive improvements in image quality as a result of these advances, the emphasis on static, semi-quantitative 'hot spot' imaging for oncologic applications has meant that the capability of PET to quantify biologically relevant parameters based on tracer kinetics has not been fully exploited. More recent advances, such as PET/MR and total-body PET, have opened up the ability to address a vast range of new research questions, from which a future expansion of applications and radiotracers appears highly likely. Many of these new applications and tracers will, at least initially, require quantitative analyses that more fully exploit the exquisite sensitivity of PET and the tracer principle on which it is based. It is also expected that they will require more sophisticated quantitative analysis methods than those that are currently available. At the same time, artificial intelligence is revolutionizing data analysis and impacting the relationship between the statistical quality of the acquired data and the information we can extract from the data. In this roadmap, leaders of the key sub-disciplines of the field identify the challenges and opportunities to be addressed over the next ten years that will enable PET to realise its full quantitative potential, initially in research laboratories and, ultimately, in clinical practice. ispartof: PHYSICS IN MEDICINE AND BIOLOGY vol:66 issue:6 ispartof: location:England status: published

We study a discrete-time model for a population subject to harvesting. A maximum annual catch H is fixed, but a minimum biomass level T must remain after harvesting. This leads to a mathematical model governed by a continuous piecewise smooth map, whose dynamics depend on two relevant parameters H and T. We combine analytical and numerical results to provide a comprehensive overview of the dynamics with special attention to discontinuity-induced (border-collision) bifurcations. We also discuss our findings in the context of harvest control rules.

In the framework of fixed point theory, many generalizations of the classical results due to Krasnosel'skii are known. One of these extensions consists in relaxing the conditions imposed on the mapping, working with k-set contractions instead of continuous and compact maps. The aim of this work if to study in detail some fixed point results of this type, and obtain a certain generalization by using star convex sets.

Huntington’s disease is a devastating neurodegenerative genetic disorder that causes progressive motor dysfunction, emotional disturbances, and cognitive impairment. Unfortunately, there is no treatment to cure or slow the progression of the disease. Neuroinflammation is one hallmark of Huntington’s disease, and modulation of neuroinflammation has been suggested as a potential target for therapeutic intervention. The relationship between neuroinflammation markers and the disease pathology is still poorly understood. To improve our understanding of neuroinflammation in Huntington’s disease, we measured translocator protein (TSPO) expression using 11C-PBR28 and simultaneous PET/MRI. Standardized-uptake-value ratios, normalized by whole brain uptake, were calculated for data acquired 60–90 min after radiotracer administration. We identified distinct patterns of regional neuroinflammation (as defined by TSPO overexpression relative to a control group) in the basal ganglia of Huntington’s disease patients. The...

The goal of this chapter is to provide the reader with a basic understanding of Positron Emission Tomography (PET) imaging and simultaneous PET and magnetic resonance (or PET/MR) imaging. These topics are presented with particular emphasis on PET as a molecular imaging tool and MRI as a structural and functional imaging tool. The chapter begins with an introduction to the underlying PET physics and a brief review of how data are acquired and reconstructed into 3D images. This includes common corrections that are applied to minimize image artifacts and improve accuracy, as well as a brief discussion of key advantages and limitations of PET and MRI and the benefits of combined PET/MR imaging. The strengths of PET as a molecular imaging technology are then presented in the context of in vivo imaging of protein targets that are relevant to schizophrenia and other neuropsychiatric disorders. This includes a basic review of PET pharmacokinetic methods used to evaluate radioligand-protein binding interactions and simpler and more feasible methods used for routine PET assessments. The final section presents a discussion of future directions and recent advances in PET/MR imaging applications.

The GE Discovery MI PET/CT system has a modular digital detector design allowing three, four, or five detector block rings that extend the axial field-of-view (FOV) from 15 to 25 cm in 5 cm increments. This study investigated the performance of the 5-ring system and compared it to 3- and 4-ring systems; the GE Discovery IQ system that uses conventional photomultiplier tubes; and the GE Signa PET/MR system that has a reduced transaxial FOV. Methods PET performance was evaluated at three different institutions. Spatial resolution, sensitivity, counting rate performance, accuracy, and image quality were measured in accordance with National Electrical Manufacturers Association NU 2-2012 standards. The mean energy resolution, mean timing resolution, and PET/CT subsystem alignment were also measured. Phantoms were used to determine the effects of varying acquisition time and reconstruction parameters on image quality. Retrospective patient scans were reconstructed with various scan durations to evaluate the impact on image quality. Results Results from all three institutions were similar. Radial/tangential/axial full width at half maximum spatial resolution measurements using the filtered back projection algorithm were 4.3/4.3/5.0 mm, 5.5/4.6/6.5 mm, and 7.4/5.0/6.6 mm at 1, 10, and 20 cm from the center of the FOV, respectively. Measured sensitivity at the center of the FOV (20.84 cps/kBq) was significantly higher than systems with reduced axial FOV. The peak noise-equivalent counting rate was 266.3 kcps at 20.8 kBq/ml, with a corresponding scatter fraction of 40.2%. The correction accuracy for count losses up to the peak noise-equivalent counting rate was 3.6%. For the 10-, 13-, 17-, 22-, 28-, and 37-mm spheres, contrast recoveries in the image quality phantom were measured to be 46.2%, 54.3%, 66.1%, 71.1%, 85.3%, and 89.3%, respectively. The mean energy and timing resolution were 9.55% and 381.7 ps, respectively. Phantom and patient images demonstrated excellent image quality, even at short acquisition times or low injected activity. Conclusion Compared to other PET/CT models, the extended axial FOV improved the overall PET performance of the 5-ring GE Discovery MI scanner. This system offers the potential to reduce scan times or injected activities through increased sensitivity.

The paper deals with a non-autonomous Lotka–Volterra type system, which in particular may include logistic growth of the prey population and hunting cooperation between predators. We focus on the existence of positive periodic solutions by using an operator approach based on the Krasnosel'skii homotopy expansion theorem. We give sufficient conditions in order that the localized periodic solution does not reduce to a steady state. Particularly, two typical expressions for the functional response of predators are discussed.

Introduction There is a growing need in clinical research domains for direct comparability between amyloid-beta (Aβ) Positron Emission Tomography (PET) measures obtained via different radiotracers and processing methodologies. Previous efforts to provide a common measurement scale fail to account for non-linearities between measurement scales that can arise from these differences. We introduce a new application of distribution mapping, based on well established statistical orthodoxy, that we call Nonlinear Distribution Mapping (NoDiM). NoDiM uses cumulative distribution functions to derive mappings between Aβ-PET measurements from different tracers and processing streams that align data based on their location in their respective distributions. Methods Utilizing large datasets of Florbetapir (FBP) from the Alzheimer's Disease Neuroimaging Initiative (n = 349 female (%) = 53) and Pittsburgh Compound B (PiB) from the Harvard Aging Brain Study (n = 305 female (%) = 59.3) and the Australian Imaging, Biomarker & Lifestyle Flagship Study of Ageing (n = 184 female (%) = 53.3), we fit explicit mathematical models of a mixture of two normal distributions, with parameter estimates from Gaussian Mixture Models, to each tracer's empirical data. We demonstrate the accuracy of these fits, and then show the ability of NoDiM to transform FBP measurements into PiB-like units. Results A mixture of two normal distributions fit both the FBP and PiB empirical data and provides a strong basis for derivation of a transfer function. Transforming Aβ-PET data with NoDiM results in FBP and PiB distributions that are closely aligned throughout their entire range, while a linear transformation does not. Additionally the NoDiM transform better matches true positive and false positive profiles across tracers. Discussion The NoDiM transformation provides a useful alternative to the linear mapping advocated in the Centiloid project, and provides improved correspondence between measurements from different tracers across the range of observed values. This improved alignment enables disparate measures to be merged on to continuous scale, and better enables the use of uniform thresholds across tracers.

Huntington's disease is a devastating neurodegenerative genetic disorder that causes progressive motor dysfunction, emotional disturbances, and cognitive impairment. Unfortunately, there is no treatment to cure or slow the progression of the disease. Neuroinflammation is one hallmark of Huntington's disease, and modulation of neuroinflammation has been suggested as a potential target for therapeutic intervention. The relationship between neuroinflammation markers and the disease pathology is still poorly understood. To improve our understanding of neuroinflammation in Huntington's disease, we measured translocator protein (TSPO) expression using

The two neuropathological hallmarks of Alzheimer's disease (AD) are amyloid-[Formula: see text] plaques and neurofibrillary tangles of tau protein. Fifteen years ago, Positron Emission Tomography (PET) with Pittsburgh Compound B (11C-PiB) enabled selective in-vivo visualization of amyloid-[Formula: see text] plaque deposits and has since provided valuable information about the role of amyloid-[Formula: see text] deposition in AD. The progression of tau deposition has been shown to be highly associated with neuronal loss, neurodegeneration, and cognitive decline. Until recently it was not possible to visualize tau deposition in-vivo, but several tau PET tracers are now available in different stages of clinical development. To date, no tau tracer has been approved by the Food and Drug Administration for use in the evaluation of AD or other tauopathies, despite very active research efforts. In this paper we review the recent developments in tau PET imaging with a focus on in-vivo findings in AD and discuss the challenges associated with tau tracer development, the status of development and validation of different tau tracers, and the clinical information these provide.

Clinical PET/MR acquisition protocols entail the use of MR contrast agents (MRCA) that could potentially affect PET quantification following MR-based attenuation correction (AC). We assessed the effect of oral and intravenous (IV) MRCA on PET quantification in PET/MR imaging.We employed two MRCA: Lumirem (oral) and Gadovist (IV). First, we determined their reference PET attenuation values using a PET transmission scan (ECAT-EXACT HR+, Siemens) and a CT scan (PET/CT Biograph 16 HI-REZ, Siemens). Second, we evaluated the attenuation of PET signals in the presence of MRCA. Phantoms were filled with clinically relevant concentrations of MRCA in a background of water and (18)F-fluoride, and imaged using a PET/CT scanner (Biograph 16 HI-REZ, Siemens) and a PET/MR scanner (Biograph mMR, Siemens). Third, we investigated the effect of clinically relevant volumes of MRCA on MR-based AC using human pilot data: a patient study employing Gadovist (IV) and a volunteer study employing two different oral MRCA (Lumirem and pineapple juice). MR-based attenuation maps were calculated following Dixon-based fat-water segmentation and an external atlas-based and pattern recognition (ATPR) algorithm.IV and oral MRCA in clinically relevant concentrations were found to have PET attenuation values similar to those of water. The phantom experiments showed that under clinical conditions IV and oral MRCA did not yield additional attenuation of PET emission signals. Patient scans showed that PET attenuation maps are not biased after the administration of IV MRCA but may be biased, however, after ingestion of iron oxide-based oral MRCA when segmentation-based AC algorithms are used. Alternative AC algorithms, such as ATPR, or alternative oral contrast agents, such as pineapple juice, can yield unbiased attenuation maps.In clinical PET/MR scenarios MRCA are not expected to lead to markedly increased attenuation of the PET emission signals. MR-based attenuation maps may be biased by oral iron oxide-based MRCA unless advanced AC algorithms are used.

Positron emission mammography (PEM) cameras are novel-dedicated PET systems optimized to image the breast. For these cameras it is essential to achieve an optimum trade-off between sensitivity and spatial resolution and therefore the main challenge for the novel cameras is to improve the sensitivity without degrading the spatial resolution. We carry out an analytical study of the effect of the different detector geometries on the photon sensitivity and the angle of incidence of the detected photons which is related to the DOI effect and therefore to the intrinsic spatial resolution. To this end, dual head detectors were compared to box and different polygon-detector configurations. Our results showed that higher sensitivity and uniformity were found for box and polygon-detector configurations compared to dual-head cameras. Thus, the optimal configuration in terms of sensitivity is a PEM scanner based on a polygon of twelve (dodecagon) or more detectors. We have shown that this configuration is clearly superior to dual-head detectors and slightly higher than box, octagon, and hexagon detectors. Nevertheless, DOI effects are increased for this configuration compared to dual head and box scanners and therefore an accurate compensation for this effect is required.

Time-of-flight (TOF) PET uses very fast detectors to improve localization of events along coincidence lines-of-response. This information is then utilized to improve the tomographic reconstruction. This work evaluates the effect of TOF upon an observer's performance for detecting and localizing focal warm lesions in noisy PET images.An advanced anthropomorphic lesion-detection phantom was scanned 12 times over 3 days on a prototype TOF PET/CT scanner (Siemens Medical Solutions). The phantom was devised to mimic whole-body oncologic (18)F-FDG PET imaging, and a number of spheric lesions (diameters 6-16 mm) were distributed throughout the phantom. The data were reconstructed with the baseline line-of-response ordered-subsets expectation-maximization algorithm, with the baseline algorithm plus point spread function model (PSF), baseline plus TOF, and with both PSF+TOF. The lesion-detection performance of each reconstruction was compared and ranked using localization receiver operating characteristics (LROC) analysis with both human and numeric observers. The phantom results were then subjectively compared to 2 illustrative patient scans reconstructed with PSF and with PSF+TOF.Inclusion of TOF information provides a significant improvement in the area under the LROC curve compared to the baseline algorithm without TOF data (P = 0.002), providing a degree of improvement similar to that obtained with the PSF model. Use of both PSF+TOF together provided a cumulative benefit in lesion-detection performance, significantly outperforming either PSF or TOF alone (P0.002). Example patient images reflected the same image characteristics that gave rise to improved performance in the phantom data.Time-of-flight PET provides a significant improvement in observer performance for detecting focal warm lesions in a noisy background. These improvements in image quality can be expected to improve performance for the clinical tasks of detecting lesions and staging disease. Further study in a large clinical population is warranted to assess the benefit of TOF for various patient sizes and count levels, and to demonstrate effective performance in the clinical environment.

Two silicon strip detectors, the Trigger Tracker(TT) and the Inner Tracker(IT) will be constructed for the LHCb experiment. Transverse momentum information extracted from the TT will be used in the Level 1 trigger. The IT is part of the main tracking system behind the magnet. Both silicon detectors will be read out using a custom-developed chip by the ASIC lab in Heidelberg. The signal-over-noise behavior and performance of various geometrical designs of the silicon sensors, in conjunction with the Beetle read-out chip, have been extensively studied in test beam experiments. Results from those experiments are presented, and have been used in the final choice of sensor geometry.

In this work a comparison between experimental and simulated data using GATE and PeneloPET Monte Carlo simulation packages is presented. All simulated setups, as well as the experimental measurements, followed exactly the guidelines of the NEMA NU 4-2008 standards using the microPET R4 scanner. The comparison was focused on spatial resolution, sensitivity, scatter fraction and counting rates performance. Both GATE and PeneloPET showed reasonable agreement for the spatial resolution when compared to experimental measurements, although they lead to slight underestimations for the points close to the edge. High accuracy was obtained between experiments and simulations of the system's sensitivity and scatter fraction for an energy window of 350-650 keV, as well as for the counting rate simulations. The latter was the most complicated test to perform since each code demands different specifications for the characterization of the system's dead time. Although simulated and experimental results were in excellent agreement for both simulation codes, PeneloPET demanded more information about the behavior of the real data acquisition system. To our knowledge, this constitutes the first validation of these Monte Carlo codes for the full NEMA NU 4-2008 standards for small animal PET imaging systems.

The presence of the naturally occurring isotope 176Lu gives rise to background count rates in LSO/LYSO crystals to be used in PET and SPECT systems. The aim of this work is to measure 176Lu background count rates and its spatial distributions in a continuous LYSO block. Our results show that the low energy component of 176Lu background is related to partial energy deposition mainly produced near the crystal edge showing a hot-perimeter artifact. Furthermore, 176Lu background rate is observed to be x10 times lower for a 100-180 keV than for a 411-611 keV energy window. Our findings indicate that when using monolithic LYSO crystal blocks, 176Lu background is not expected to significantly deteriorate the performance of single photon detection systems.

Monte Carlo simulations were carried out in order to evaluate the performance of readout solutions for monolithic LYSO blocks, considering several 2D array configurations of discrete SiPMs. Results were compared to conventional multianode PMT readout. Our findings show that a detector module based on an array of 8×8 discrete SiPM may lead to better energy resolution and comparable spatial resolution. Our work shows the feasibility of using discrete SiPMs as readout for monolithic scintillator-based detector modules.

The introduction of fast scintillators with good stopping power for 511 keV photons has renewed interest in Time-of-Flight Positron Emission Tomography (TOF-PET). The ability to measure the difference between the arrival times of a pair of photons originating from positron annihilation improves the image signal-to-noise ratio (SNR). The level of improvement depends upon the extent and distribution of the positron activity and the time resolution of the PET scanner. While specific estimates can be made for phantom imaging, the impact of TOF-PET is more difficult to quantify in clinical situations. The results presented here quantify the benefit of TOF in a challenging phantom experiment and then assesses both qualitatively and quantitatively the impact of incorporating TOF information into the reconstruction of clinical studies. A clear correlation between patient body mass index (BMI) and gain in SNR was observed in this study involving 100 oncology patient studies, with a gain due to TOF ranging from 1.2 to 2, which is consistent with the 590 ps time resolution of the TOF-PET scanner. The visual comparison of TOF and non-TOF images performed by two nuclear medicine physicians confirmed the advantages of incorporating TOF into the reconstruction, advantages that include better definition of small lesions and image details, improved uniformity, and noise reduction.

Positron Emission Tomography (PET) techniques have gained an important role in the diagnosis of human diseases as well as for pharmaceutical and biomedical research. In order to best optimize their capabilities, evaluation of their performance has to be achieved through standardized methodology from specific standards. The aim of this work was to assess the performance evaluation of the microPET R4 system for imaging rodents according to the new NEMA NU 4-2008 standards and compare it against its previous evaluation according the adapted clinical NEMA NU 2-2001. All measurements were made for an energy window of 350-650 keV. Spatial resolution of 2.12 mm FWHM in the radial direction, 2.66 mm FWHM in the tangential direction and 2.23 mm FWHM in the axial direction was measured in the centre of the axial FOV. Scatter fraction for mouse and rat phantoms were found to be 9.5% and 22% respectively. The maximum noise-equivalent count rate (NECR) was 110 kcps at 121.3 MBq for the rat phantom 287 kcp at 129.8 MBq for the mouse phantom. The absolute sensitivity of the scanner was found to be 1.66% at the centre of the field of view.

Monte Carlo simulations were carried out in order to guide the choice of crystal block material and thickness for a small FOV PET/SPECT camera. A continuous crystal block of 50mm x 50mm was simulated considering several thickness (8 mm, 16 mm and 32 mm) and two scintillation crystal types(LSO:Ce and NaI:Tl). Detection module parameters like spatial resolution at centre and border of FOV, efficiency and energy resolution were evaluated. Despite there is a common opinion that LSO is a less valuable material for SPECT detection, our findings demonstrate that LSO crystal blocks have interesting design features for the development of an hybrid SPECT and PET system. Our results show that by adequate corrections of non-linearity of a thick crystal block response, a high detection efficiency can be preserved (nearly 80% for PET and 99.9% for SPECT) without compromising high spatial resolution (about 1.9 mm for PET and 1.45 mm for SPECT).

The LHCb experiment, which is currently under construction at the Large Hadron Collider~(CERN, Geneva), is designed to study $CP$ violation and find rare decays in the $B$ meson system. To achieve the physics goals the LHCb detector must have excellent tracking performance. An important element of the LHCb tracking system is the Silicon Tracker, which covers a sensitive surface of about 12~m$^2$ with silicon microstrip detectors and includes about 272k readout channels. It uses up to 132~cm long detector modules with readout strips of up to 38~cm in length and up to 57~cm long Kapton interconnects in between sensors and readout hybrids. The production of detector modules has been completed recently and the detector is currently under installation. A rigorous quality assurance programme has been performed to ensure that the detector modules meet the mechanical and electrical requirements and study their various characteristics. In this paper, the detector design, the module production steps, and the module quality assurance programme are briefly described.

Molecular imaging is reshaping clinical practice in the last decades, providing practitioners with non-invasive ways to obtain functional in-vivo information on a diversity of relevant biological processes. The use of molecular imaging techniques in preclinical research is equally beneficial, but spreads more slowly due to the difficulties to justify a costly investment dedicated only to animal scanning. An alternative for lowering the costs is to repurpose parts of old clinical scanners to build new preclinical ones. Following this trend, we have designed, built, and characterized the performance of a portable system that can be attached to a clinical gamma-camera to make a preclinical single photon emission computed tomography scanner. Our system offers an image quality comparable to commercial systems at a fraction of their cost, and can be used with any existing gamma-camera with just an adaptation of the reconstruction software.

This paper shows a feasibility study on the use of discrete SiPMs to read out monolithic scintillator-based detectors for use in molecular imaging applications. Monte Carlo simulations are carried out in order to evaluate the basic performance of 8 × 8 arrays of discrete SiPMs with different PDE values and compare it to conventional 64 channel multi-anode PMT (MA-PMT) readout. A detailed optical transport model was incorporated into the Monte Carlo simulation and a detector module based on a monolithic scintillator crystal of 50 × 50 × 4 mm3 coupled to a MA-PMT was built for experimental validation. The effect of the SiPM dynamic range was also investigated by including a model of the saturation effects into the optical transport simulation. The results show that a detector module based on an array of 8 × 8 discrete SiPM devices (3 × 3 mm2 and PDE > 32%) is feasible as a replacement of a 64 channel MA-PMT in order to read out large monolithic crystals for MR-compatible gamma cameras.

Noninvasive biomarkers of early neuronal injury may help identify cognitively normal individuals at risk of developing Alzheimer’s disease (AD). A recent diffusion-weighted imaging (DWI) method allows assessing cortical microstructure via cortical mean diffusivity (cMD), suggested to be more sensitive than macrostructural neurodegeneration. Here, we aimed to investigate the association of cMD with amyloid-β and tau pathology in older adults, and whether cMD predicts longitudinal cognitive decline, neurodegeneration and clinical progression. The study sample comprised n = 196 cognitively normal older adults (mean[SD] 72.5 [9.4] years; 114 women [58.2%]) from the Harvard Aging Brain Study. At baseline, all participants underwent structural MRI, DWI, 11C-Pittsburgh compound-B-PET, 18F-flortaucipir-PET imaging, and cognitive assessments. Longitudinal measures of Preclinical Alzheimer Cognitive Composite-5 were available for n = 186 individuals over 3.72 (1.96)-year follow-up. Prospective clinical follow-up was available for n = 163 individuals over 3.2 (1.7) years. Surface-based image analysis assessed vertex-wise relationships between cMD, global amyloid-β, and entorhinal and inferior-temporal tau. Multivariable regression, mixed effects models and Cox proportional hazards regression assessed longitudinal cognition, brain structural changes and clinical progression. Tau, but not amyloid-β, was positively associated with cMD in AD-vulnerable regions. Correcting for baseline demographics and cognition, increased cMD predicted steeper cognitive decline, which remained significant after correcting for amyloid-β, thickness, and entorhinal tau; there was a synergistic interaction between cMD and both amyloid-β and tau on cognitive slope. Regional cMD predicted hippocampal atrophy rate, independently from amyloid-β, tau, and thickness. Elevated cMD predicted progression to mild cognitive impairment. Cortical microstructure is a noninvasive biomarker that independently predicts subsequent cognitive decline, neurodegeneration and clinical progression, suggesting utility in clinical trials.

LHCb is one of the experiments of the Large Hadron Collider at CERN, dedicated to B-physics and CP-violation measurements. To fully exploit the physics potential, a good tracking performance with high efficiency in a high particle density environment close to the beam pipe is required. Silicon strip detectors with large read-out pitch and long strips will be used for the LHCb Inner Tracker after the magnet and the Trigger Tracker station in front of the magnet. We report here about the design of the Silicon Tracker, test beam results and the electrical tests foreseen during module production.