Age-related reduction of hemispheric asymmetry by pigeons: A behavioral and FDG-PET imaging investigation of visual discrimination.

Pigeons are long-lived and slowly aging animals that present a distinct opportunity to further our understanding of age-related brain changes. Generally, for pigeons, the left hemisphere contributes to discrimination of local information, whereas the right contributes to processing of global information. The function of each hemisphere may be examined by covering one eye, as the optic nerves decussate almost completely in birds, directing the majority of visual information to the contralateral hemisphere. Using this eye-capping technique, we investigated pigeons' ability to select grains from among grit while under binocular and monocular viewing conditions, across three different age groups. Prior to the grit-grain discrimination task, pigeons were injected with a radioactive tracer, which was taken up by the brain as the pigeons performed the task. Upon completion of the discrimination task, the pigeons' brains were imaged via [18F] fluorodeoxyglucose positron emission tomography (FDG-PET) scans. This process allowed us to compare hemispheric activity during the discrimination task for each individual within each age group. The Very Old subjects showed significantly worse discrimination performance compared to the Adult and Old subjects, particularly when needing to search primarily with their right hemisphere. Furthermore, the Very Old subjects did not show differences in hemispheric activation when performing the task, whereas the left hemisphere was most active for the Adult and Old groups. To our knowledge, this is the first study to use FDG-PET imaging to evaluate whether the pigeon brain shows evidence of age-related reduction in hemispheric asymmetry during a visual discrimination task.

Regional hypometabolism in the 3xTg mouse model of Alzheimer's disease.

Alzheimer's disease (AD) is a progressive age-related neurodegenerative disease. Although neurofibrillary tangles and amyloid beta are classic hallmarks of AD, the earliest deficits in AD progression may be caused by unknown factors. One suspected factor has to do with brain energy metabolism. To investigate this factor, brain metabolic activity in 3xTg-AD mice and age-matched controls were measured with FDG-PET. Significant hypometabolic changes (p < .01) in brain metabolism were detected in the cortical piriform and insular regions of AD brains relative to controls. These regions are associated with olfaction, which is a potential clinical marker for AD progression as well as neurogenesis. The activity of the terminal component of the mitochondrial respiratory chain (complex IV) and the expression of complex I-V were significantly decreased (p < .05), suggesting that impaired metabolic activity coupled with impaired oxidative phosphorylation leads to decreased mitochondrial bioenergetics and subsequent Neurodegeneration. Although there is an association between neuroinflammatory pathological markers (microglial) and hypometabolism in AD, there was no association found between neuropathological (Aß, tau, and astrocytes) and functional changes in AD sensitive brain regions, also suggesting that brain hypometabolism occurs prior to AD pathology. Therefore, targeting metabolic mechanisms in cortical piriform and insular regions at early stages may be a promising approach for preventing, slowing, and/or blocking the onset of AD and preserving neurogenesis.

Fracture Risk Indices From DXA-Based Finite Element Analysis Predict Incident Fractures Independently From FRAX: The Manitoba BMD Registry.

OBJECTIVE: Finite element analysis (FEA) is a computational method to predict the behavior of materials under applied loading. We developed a software tool that automatically performs FEA on dual-energy X-ray absorptiometry hip scans to generate site-specific fracture risk indices (FRIs) that reflect the likelihood of hip fracture from a sideways fall. This longitudinal study examined associations between FRIs and incident fractures. METHODS: Using the Manitoba Bone Mineral Density (BMD) Registry, femoral neck (FN), intertrochanter (IT), and subtrochanter (ST) FRIs were automatically derived from 13,978 anonymized dual-energy X-ray absorptiometry scans (Prodigy, GE Healthcare) in women and men aged 50 yr or older (mean age 65 yr). Baseline covariates and incident fractures were assessed from population-based data. We compared c-statistics for FRIs vs FN BMD alone and fracture risk assessment (FRAX) probability computed with BMD. Cox regression was used to estimate hazard ratios and 95% confidence intervals (95% CIs) for incident hip, major osteoporotic fracture (MOF) and non-hip MOF adjusted for relevant covariates including age, sex, FN BMD, FRAX probability, FRAX risk factors, and hip axis length (HAL). RESULTS: During mean follow-up of 6 yr, there were 268 subjects with incident hip fractures, 1003 with incident MOF, and 787 with incident non-hip MOF. All FRIs gave significant stratification for hip fracture (c-statistics FN-FRI: 0.76, 95% CI 0.73-0.79, IT-FRI 0.74, 0.71-0.77; ST-FRI 0.72, 0.69-0.75). FRIs continued to predict hip fracture risk even after adjustment for age and sex (hazard ratio per standard deviation FN-FRI 1.89, 95% CI 1.66-2.16); age, sex, and BMD (1.26, 1.07-1.48); FRAX probability (1.30, 1.11-1.52); FRAX probability with HAL (1.26, 1.05-1.51); and individual FRAX risk factors (1.32, 1.09-1.59). FRIs also predicted MOF and non-hip MOF, but the prediction was not as strong as for hip fracture. SUMMARY: Automatically-derived FN, IT, and ST FRIs are associated with incident hip fracture independent of multiple covariates, including FN BMD, FRAX probability and risk factors, and HAL.

Fully automated analysis of attenuation-corrected SPECT for the long-term prediction of acute myocardial infarction.

BACKGROUND: Most prior studies assessing the prognostic value of SPECT myocardial perfusion imaging (MPI) have used semi-quantitative visual analysis. We assessed the feasibility of large-scale fully automated quantitative analysis of SPECT MPI to predict acute myocardial infarction (AMI). Additionally, we examined the impact of attenuation correction (AC) in automated strategies. METHODS AND RESULTS: 5960 patients underwent rest/stress SPECT MPI with AC. Left ventricular (LV) segmentation, contour QC check, and quantitation of stress and ischemic total perfusion deficit (sTPD, iTPD) were performed. Only contours flagged for potential errors by QC were visually checked (10%). During long-term follow-up (6.1 ± 2.7 years), 522 patients (9%) had AMI. In Cox models, adjusted for ejection fraction (LVEF) and other relevant covariates, there was a stepwise increase in risk hazard ratios by quartile for sTPD (Q1: 1.00, Q2: 1.26, Q3: 1.66, Q4: 1.79; P < 0.0001) and iTPD (Q1: 1.00, Q2: 1.26, Q3: 1.66, Q4: 1.79; P < 0.0001). Area under curve for AMI prediction by automated measures was similar for AC and non-AC data (sTPD: 0.63 vs 0.64, P = 0.85; iTPD: 0.61 vs 0.61, P = 0.70). Higher AUCs for both AC and non-AC data were seen for AMI occurring in the first 1 year of follow-up (sTPD: 0.71, 0.72; iTPD: 0.70, 0.68). CONCLUSIONS: Fully automated sTPD was an independent predictor of future AMI events even after adjusting for LVEF and other relevant covariates. AC did not significantly impact predictive accuracy.

Long-Term Proton Pump Inhibitor Use Is Not Associated With Changes in Bone Strength and Structure.

OBJECTIVES: Multiple studies have reported an association between proton pump inhibitor (PPI) use and fracture. However, the causality of this association is questionable, as there is not a well defined mechanism of action, nor is there evidence of an effect on PPIs on areal bone mineral density (aBMD) using dual photon X-ray absorptiometry (DXA). It is possible that PPIs may induce changes in bone structure which would predispose to fracture in the absence of changes in aBMD. We used three-dimensional quantitative computed tomography (3D-QCT) imaging to determine if long-term PPI use was associated with structural changes in bone independent of aBMD. METHODS: We enrolled a sample of long-term (≥5 years) PPI users matched to a similar cohort of persons with no PPI use in the previous 5 years. All subjects underwent assessment of aBMD using DXA, volumetric BMD using 3D-QCT, as well as markers of bone metabolism. Measures of bone strength, including buckling ratio and section modulus, were also compared between the two samples. RESULTS: 104 subjects were enrolled (52 PPI users and 52 PPI non-users). There were no differences detected in standard BMD, volumetric BMD, markers of bone metabolism or measures of bone strength between the two groups. CONCLUSIONS: Long-term PPI use is not associated with any changes in bone mineral density or bone strength that would predispose to an increased risk of fracture. These findings provide further evidence that the association between PPI use and fracture is not causal.

Development of a PET scanner for simultaneously imaging small animals with MRI and PET.

Recently, positron emission tomography (PET) is playing an increasingly important role in the diagnosis and staging of cancer. Combined PET and X-ray computed tomography (PET-CT) scanners are now the modality of choice in cancer treatment planning. More recently, the combination of PET and magnetic resonance imaging (MRI) is being explored in many sites. Combining PET and MRI has presented many challenges since the photo-multiplier tubes (PMT) in PET do not function in high magnetic fields, and conventional PET detectors distort MRI images. Solid state light sensors like avalanche photo-diodes (APDs) and more recently silicon photo-multipliers (SiPMs) are much less sensitive to magnetic fields thus easing the compatibility issues. This paper presents the results of a group of Canadian scientists who are developing a PET detector ring which fits inside a high field small animal MRI scanner with the goal of providing simultaneous PET and MRI images of small rodents used in pre-clinical medical research. We discuss the evolution of both the crystal blocks (which detect annihilation photons from positron decay) and the SiPM array performance in the last four years which together combine to deliver significant system performance in terms of speed, energy and timing resolution.

The prognostic value of single photon emission computed tomography (SPECT) myocardial perfusion imaging is independent of left ventricular size.

Many variables have been shown to impact accuracy and prognostic power of myocardial perfusion imaging (MPI); however, effects of left ventricular size have not been extensively studied. In particular, perfusion defects in smaller hearts could be overlooked due to partial volume averaging, potentially reducing the prognostic power of MPI. We determined stress total perfusion deficit (TPD) and rest end diastolic volume (REDV) from single photon emission computed tomography (SPECT) MPI in consecutive patients without pathologically dilated left ventricles. Area under the curve (AUC) and Cox regression analysis were used to assess prediction of subsequent major adverse cardiac events [MACE-death, hospitalized acute myocardial infarction (AMI), hospitalized unstable angina, late revascularization]. Analyses were stratified by sex and REDV tertile. The analytic population included 2,503 patients (965 men and 1,538 women). Outcomes were assessed over an average of 6.4±2.3 years. MACE was observed in 254 (26.3%) of 965 men and 261 (17.0%) of 1,538 women. Stress TPD showed significant AUCs for stratifying MACE risk regardless of sex and REDV tertile (all P<0.05). In Cox regression analysis, increasing stress TPD (but not REDV) was associated with MACE in both men and women. There was no significant TPD*REDV interaction. In conclusion, we found the prognostic power of SPECT MPI to be independent of left ventricular size.

Optimizing stress-only myocardial perfusion imaging: a clinical prediction model to improve patient selection.

BACKGROUND: Stress-only single photon emission computed tomography myocardial perfusion imaging (MPI) offers numerous advantages in terms of improved workflow, cost and radiation reduction but is currently not widely utilized due to challenges in selecting appropriate patients for this technique. METHODS: Data from 5959 individuals were used to derive (N = 4018) and validate (N = 1941) a binomial logistic regression model to predict normal stress MPI studies (stress total perfusion deficit  < 4%, ejection fraction ≥ 50%). Model performance was analyzed using receiver operator characteristic curves. A simplified point-scoring system was developed and its impact on imaging workflow was assessed. RESULTS: Significant predictors of abnormal vs. normal stress MPI included male sex, age > 65 years, cardiomyopathy, congestive heart failure, myocardial infarction, angina, and pharmacological stress. The final model and simplified scoring system were associated with areas under the curve of 0.81 (95% CI 0.79-0.83) and 0.80 (95% CI 0.79-0.82) in the validation group, respectively. Use of the scoring system was estimated to result in a decrease of 56.5% in the number of non-contributory imaging studies acquired with minimal patient rescheduling. CONCLUSION: A prediction tool derived from simple clinical information can identify candidates for stress-only MPI studies with a beneficial impact on departmental workflow.

Do Epilepsy Patients with Cognitive Impairment Have Alzheimer's Disease-like Brain Metabolism?

Although not classically considered together, there is emerging evidence that Alzheimer's disease (AD) and epilepsy share a number of features and that each disease predisposes patients to developing the other. Using machine learning, we have previously developed an automated fluorodeoxyglucose positron emission tomography (FDG-PET) reading program (i.e., MAD), and demonstrated good sensitivity (84%) and specificity (95%) for differentiating AD patients versus healthy controls. In this retrospective chart review study, we investigated if epilepsy patients with/without mild cognitive symptoms also show AD-like metabolic patterns determined by the MAD algorithm. Scans from a total of 20 patients with epilepsy were included in this study. Because AD diagnoses are made late in life, only patients aged ≥40 years were considered. For the cognitively impaired patients, four of six were identified as MAD+ (i.e., the FDG-PET image is classified as AD-like by the MAD algorithm), while none of the five cognitively normal patients was identified as MAD+ (χ2 = 8.148, p = 0.017). These results potentially suggest the usability of FDG-PET in prognosticating later dementia development in non-demented epilepsy patients, especially when combined with machine learning algorithms. A longitudinal follow-up study is warranted to assess the effectiveness of this approach.

Quantitative computed tomography in porcine lung injury with variable versus conventional ventilation: recruitment and surfactant replacement.

OBJECTIVES: Biologically variable ventilation improves lung function in acute respiratory distress models. If enhanced recruitment is responsible for these results, then biologically variable ventilation might promote distribution of exogenous surfactant to nonaerated areas. Our objectives were to confirm model predictions of enhanced recruitment with biologically variable ventilation using computed tomography and to determine whether surfactant replacement with biologically variable ventilation provides additional benefit in a porcine oleic acid injury model. DESIGN: Prospective, randomized, controlled experimental animal investigation. SETTING: University research laboratory. SUBJECTS: Domestic pigs. INTERVENTIONS: Standardized oleic acid lung injury in pigs randomized to conventional mechanical ventilation or biologically variable ventilation with or without green dye labeled surfactant replacement. MEASUREMENTS AND MAIN RESULTS: Computed tomography-derived total and regional masses and volumes were determined at injury and after 4 hrs of ventilation at the same average low tidal volume and minute ventilation. Hemodynamics, gas exchange, and lung mechanics were determined hourly. Surfactant distribution was determined in postmortem cut lung sections. Biologically variable ventilation alone resulted in 7% recruitment of nonaerated regions (p < .03) and 15% recruitment of nonaerated and poorly aerated regions combined (p < .04). Total and normally aerated regional volumes increased significantly with biologically variable ventilation, biologically variable ventilation with surfactant replacement, and conventional mechanical ventilation with surfactant replacement, while poorly and nonaerated regions decreased after 4 hrs of ventilation with biologically variable ventilation alone (p < .01). Biologically variable ventilation showed the greatest improvement (p < .003, biologically variable ventilation vs. all other groups). Hyperaerated regional gas volume increased significantly with biologically variable ventilation, biologically variable ventilation with surfactant replacement, and conventional mechanical ventilation with surfactant replacement. Biologically variable ventilation was associated with restoration of respiratory compliance to preinjury levels and significantly greater improvements in gas exchange at lower peak airway pressures compared to all other groups. Paradoxically, gas exchange and lung mechanics were impaired to a greater extent initially with biologically variable ventilation with surfactant replacement. Peak airway pressure was greater in surfactant-treated animals with either ventilation mode. Surfactant was distributed to the more caudal/injured lung sections with biologically variable ventilation. CONCLUSIONS: Quantitative computed tomography analysis confirms lung recruitment with biologically variable ventilation in a porcine oleic acid injury model. Surfactant replacement with biologically variable ventilation provided no additional recruitment benefit and may in fact be harmful.

Viability and proliferation potential of adipose-derived stem cells following labeling with a positron-emitting radiotracer.

PURPOSE: Adipose-derived stem cells (ASCs) have promising potential in regenerative medicine and cell therapy. Our objective is to examine the biological function of the labeled stem cells following labeling with a readily available positron emission tomography (PET) tracer, (18)F-fluoro-2-deoxy-D: -glucose (FDG). In this work we characterize labeling efficiency through assessment of FDG uptake and retention by the ASCs and the effect of FDG on cell viability, proliferation, transdifferentiation, and cell function in vitro using rat ASCs. METHODS: Samples of 10(5) ASCs (from visceral fat tissue) were labeled with concentrations of FDG (1-55 Bq/cell) in 0.75 ml culture medium. Label uptake and retention, as a function of labeling time, FDG concentration, and efflux period were measured to determine optimum cell labeling conditions. Cell viability, proliferation, DNA structure damage, cell differentiation, and other cell functions were examined. Non-labeled ASC samples were used as a control for all experimental groups. Labeled ASCs were injected via tail vein in several healthy rats and initial cell biodistribution was assessed. RESULTS: Our results showed that FDG uptake and retention by the stem cells did not depend on FDG concentration but on labeling and efflux periods and glucose content of the labeling and efflux media. Cell viability, transdifferentiation, and cell function were not greatly affected. DNA damage due to FDG radioactivity was acute, but reversible; cells managed to repair the damage and continue with cell cycles. Over all, FDG (up to 25 Bq/cell) did not impose severe cytotoxicity in rat ASCs. Initial biodistribution of the FDG-labeled ASCs was 80% + retention in the lungs. In the delayed whole-body images (2-3 h postinjection) there was some activity distribution resembling typical FDG uptake patterns. CONCLUSION: For in vivo cell tracking studies with PET tracers, the parameter of interest is the amount of radiotracer that is present in the cells being labeled and consequent biological effects. From our study we developed a labeling protocol for labeling ASCs with a readily available PET tracer, FDG. Our results indicate that ASCs can be safely labeled with FDG concentration up to 25 Bq/cell, without compromising their biological function. A labeling period of 90 min in glucose-free medium and efflux of 60 min in complete media resulted in optimum label retention, i.e., 60% + by the stem cells. The initial biodistribution of the implanted FDG-labeled stem cells can be monitored using microPET imaging.

Alzheimer's Disease-Related Metabolic Pattern in Diverse Forms of Neurodegenerative Diseases.

Dementia is broadly characterized by cognitive and psychological dysfunction that significantly impairs daily functioning. Dementia has many causes including Alzheimer's disease (AD), dementia with Lewy bodies (DLB), and frontotemporal lobar degeneration (FTLD). Detection and differential diagnosis in the early stages of dementia remains challenging. Fueled by AD Neuroimaging Initiatives (ADNI) (Data used in preparation of this article were obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. As such, the investigators within ADNI contributed to the design and implementation of ADNI and/or provided data but did not participate in analysis or writing of this report.), a number of neuroimaging biomarkers for AD have been proposed, yet it remains to be seen whether these markers are also sensitive to other types of dementia. We assessed AD-related metabolic patterns in 27 patients with diverse forms of dementia (five had probable/possible AD while others had atypical cases) and 20 non-demented individuals. All participants had positron emission tomography (PET) scans on file. We used a pre-trained machine learning-based AD designation (MAD) framework to investigate the AD-related metabolic pattern among the participants under study. The MAD algorithm showed a sensitivity of 0.67 and specificity of 0.90 for distinguishing dementia patients from non-dementia participants. A total of 18/27 dementia patients and 2/20 non-dementia patients were identified as having AD-like patterns of metabolism. These results highlight that many underlying causes of dementia have similar hypometabolic pattern as AD and this similarity is an interesting avenue for future research.

Changes in Metabolic Activity and Gait Function by Dual-Task Cognitive Game-Based Treadmill System in Parkinson's Disease: Protocol of a Randomized Controlled Trial.

Balance and gait impairments, and consequently, mobility restrictions and falls are common in Parkinson's disease (PD). Various cognitive deficits are also common in PD and are associated with increased fall risk. These mobility and cognitive deficits are limiting factors in a person's health, ability to perform activities of daily living, and overall quality of life. Community ambulation involves many dual-task (DT) conditions that require processing of several cognitive tasks while managing or reacting to sudden or unexpected balance challenges. DT training programs that can simultaneously target balance, gait, visuomotor, and cognitive functions are important to consider in rehabilitation and promotion of healthy active lives. In the proposed multi-center, randomized controlled trial (RCT), novel behavioral positron emission tomography (PET) brain imaging methods are used to evaluate the molecular basis and neural underpinnings of: (a) the decline of mobility function in PD, specifically, balance, gait, visuomotor, and cognitive function, and (b) the effects of an engaging, game-based DT treadmill walking program on mobility and cognitive functions. Both the interactive cognitive game tasks and treadmill walking require continuous visual attention, and share spatial processing functions, notably to minimize any balance disturbance or gait deviation/stumble. The ability to "walk and talk" normally includes activation of specific regions of the prefrontal cortex (PFC) and the basal ganglia (site of degeneration in PD). The PET imaging analysis and comparison with healthy age-matched controls will allow us to identify areas of abnormal, reduced activity levels, as well as areas of excessive activity (increased attentional resources) during DT-walking. We will then be able to identify areas of brain plasticity associated with improvements in mobility functions (balance, gait, and cognition) after intervention. We expect the gait-cognitive training effect to involve re-organization of PFC activity among other, yet to be identified brain regions. The DT mobility-training platform and behavioral PET brain imaging methods are directly applicable to other diseases that affect gait and cognition, e.g., cognitive vascular impairment, Alzheimer's disease, as well as in aging.

Practical Aspects of 18F-FDG PET When Receiving 18F-FDG from a Distant Supplier.

UNLABELLED: With PET becoming more widely used, there is an increase in the number of imaging centers being forced to rely on distant suppliers of (18)F-FDG. Because of the large distances between major urban centers, this is particularly true for PET centers in Canada. METHODS: Our PET center, located in Winnipeg, Manitoba, Canada, currently purchases (18)F-FDG from a commercial vendor located more than 1,000 km from Winnipeg, necessitating transport by commercial airline cargo. This dependence on air transport and a distant supplier creates a situation in which our (18)F-FDG supply is less reliable than it would be with onsite production. In this article, we offer insight into the obstacles we have encountered in imaging with a distant supplier of (18)F-FDG and the solutions we have implemented to minimize the disruption to our patients and maximize the number of scans performed each year. RESULTS: The development of contingency plans and protocols designed to suit our operating environment has allowed us to increase the number of patient scans obtained from 659 in year 1 to 993 in year 3, an increase of 51%, despite an increase in our actual number of scan days of only 24%. (18)F-FDG injection timetables are presented for a variety of scenarios including normal delivery, low shipped activity, and delayed delivery. CONCLUSION: Through the careful establishment of contingency protocols and management of (18)F-FDG shipments, patient throughput can be increased and disruptions minimized.

A study of inter-crystal scatter in dual-layer offset scintillator arrays for brain-dedicated PET scanners.

A dual-layer offset (DLO) detector enables depth-of-interaction (DOI) through light sharing between two layers of scintillation arrays with a single-ended readout (SER) scheme. However, the SER scheme in DLO detectors may lead to a layer misassignment when inter-crystal scattering occurs. The aim of this work is to study inter-crystal scattering and evaluate the effects of layer misidentifications in DLO detectors on the performance of scanners suitable for a brain-dedicated PET insert. The influence of layer misidentification on the coincidence response functions (CRFs) of 3 different DLO detectors with total/front/back layer thicknesses of 15/6/9 mm, 20/8/12 mm, and 25/7.5/17.5 mm and a crystal width of about 3 mm was studied through Monte Carlo simulations. To overcome layer misidentification, we studied a practical DLO detector design in which each layer can be read out independently through a discrete-layer readout (DLR) scheme where light sharing between the layers is avoided. The CRFs of the mentioned DLO detectors assuming SER and DLR were analyzed. To evaluate the effects of layer misidentification on image quality, images of a Derenzo-like phantom were also reconstructed for all DLO and their equivalent single layer PET scanners. Our analysis showed that layer misassignments due to inter-crystal scatter in DLO detectors mainly has effect on the full-width at tenth maximum of the CRFs. According to the reconstructed images of the phantom, no significant improvements in the quality of the images were seen when SER was replaced with DLR. The results suggest that layer misidentification in DLO detectors does not play an important role in the quality of the PET images.

Count rate performance of brain-dedicated PET scanners: a Monte Carlo simulation study.

In recent years, there has been a renewed interest in brain-dedicated PET imaging systems, particularly in the context of combined PET/MR imaging. We are currently designing a brain-dedicated PET insert suitable for an ultra-high field brain-dedicated MR scanner, the Siemens Magnetom 7T MR scanner. In this paper, an investigation on the count rate performance of several possible detectors through a series of Monte Carlo simulations is reported. Brain-dedicated PET scanners with a lutetium oxyorthosilicate scintillator and a detector area of 0.04 (1 crystal per detector) to 101.37 (2500 crystals per detector) cm2, detector thickness of 10 to 20 mm and a fixed crystal pitch of ~2 mm were simulated. The count rate performance of each scanner was evaluated as a function of detector deadtime type and constant, coincidence timing window and lower level discriminator. Also, the effects of activity outside the field-of-view (FOV) on the count rate performance of each scanner were studied. For each detector geometry and performance metric, the scanner singles rate, scanner sensitivity and noise equivalent count rate as a function of activity in the FOV were measured. It was seen that scanners with detectors comprised a few crystal elements showed reduced scanner sensitivity due to a high number of inter-detector scattering. The count rate performance of scanners with large detectors, on the other hand, was mainly determined by the deadtime properties of the detectors. A model for the count rate performance of the scanner with each studied detector is presented in this work.

Demonstrating Compliance With Proposed Reduced Lens of Eye Dose Limits in Nuclear Medicine Settings.

Based on ongoing research on ionizing radiation thresholds for cataracts, the International Commission on Radiological Protection has proposed new guidelines lowering the annual occupational lens of eye dose limit from 150 mSv to 20 mSv. The International Atomic Energy Agency has operationalized these new guidelines. Subsequently, national/regional radiation protection regulators are reviewing their lens of eye dose limits with an aim of moving towards the proposed new limits, resulting in licensees having to demonstrate compliance. In health care settings, fluoroscopic interventional practices generally have higher lens of eye doses and nuclear medicine settings generally have lower doses. A prospective cohort (n = 19) of nuclear medicine technologists wore dedicated lens of eye dosimeters for a 3 mo period synchronized with their body dosimeter schedules. The lens of eye dosimeters were validated to have a linear response in the anticipated dose ranges. The participants worked in a relatively high-volume nuclear medicine practice, which included general and cardiac, positron emission tomography/computed tomography, radiopharmacy, and cyclotron operations. The annualized dose ranges were 0.0-3.68 mSv (lens of eye) and 0.48-4.72 mSv (whole body). There was a good correlation between lens of eye and body dosimeter readings (R = 0.67). There were no significant differences in lens of eye dose by work type, worker sex, or side on which the dosimeter was worn. The findings should be generalizable to other similar practices, especially in North America, and should be sufficient to demonstrate regulatory compliance in nuclear medicine settings with the proposed new lens of eye dose limits.

Towards a second-generation PET/MR insert with enhanced timing and count rate performance.

Previously we have developed a first-generation PET insert prototype for small animal PET/MR imaging, which used resistor-based charge division multiplexing circuits and SensL B-series silicon photomultipliers (SiPMs). In this work we present results from a second-generation readout board with improved timing and count rate performance. Three detector boards were tested: the first-generation readout board with SensL SPMArray4B (SiPM-B), the second-generation readout board with SensL ArrayC-30035-16P-PCB (SiPM-C) using the 'fast' outputs for timing, and the second generation board using Hamamatsu S11361-3050AE-04 MPPC arrays. Timing data were obtained with detector modules in coincidence with a single-pixel SensL MicroFJ-SMA-30035 reference detector and acquired using standard NIM electronics, while count rate data were acquired using the OpenPET data acquisition electronics system. The full-width at half-maximum (FWHM) coincidence time resolution (CTR) for the SiPM-B, SiPM-C and MPPC designs were 2600 ± 200 ps, 550 ± 50 ps, and 570 ± 30 ps, respectively. OpenPET waveform capture determined the mean signal durations, measured as time above 10% of the maximum amplitude, were 1850 ± 150 ns, 600 ± 25 ns, and 350 ± 25 ns, respectively, where the short signal of the MPPC resulted in reduced pileup effects at higher count rates. Decaying source measurements showed a non-paralyzable dead time of 1.30-1.41 µs for all three detectors tested, which was limited by the signal capture and processing time of the OpenPET system.

Blood Flow and Glucose Metabolism Dissociation in the Putamen Is Predictive of Levodopa Induced Dyskinesia in Parkinson's Disease Patients.

Background: The forefront treatment of Parkinson's disease (PD) is Levodopa. When patients are treated with Levodopa cerebral blood flow is increased while cerebral metabolic rate is decreased in key subcortical regions including the putamen. This phenomenon is especially pronounced in patients with Levodopa-induced dyskinesia (LID). Method: To study the effect of clinically-determined anti-parkinsonian medications, 10 PD patients (5 with LID and 5 without LID) have been scanned with FDG-PET (a probe for glucose metabolism) and perfusion MRI (a probe for cerebral blood flow) both when they are ON and OFF medications. Patients additionally underwent resting state fMRI to detect changes in dopamine-mediated cortico-striatal connectivity. The degree of blood flow-glucose metabolism dissociation was quantified by comparing the FDG-PET and perfusion MRI data. Results: A significant interaction effect (imaging modality × medication; blood flow-glucose metabolism dissociation) has been found in the putamen (p = 0.023). Post-hoc analysis revealed that anti-parkinsonian medication consistently normalized the pathologically hyper-metabolic state of the putamen while mixed effects were observed in cerebral blood flow changes. This dissociation was especially predominant in patients with LID compared to those without. Unlike the prior study, this differentiation was not observed when cortico-striatal functional connectivity was assessed. Conclusion: We confirmed striatal neurovascular dissociation between FDG-PET and perfusion MRI in response to clinically determined anti-parkinsonian medication. We further proposed a novel analytical method to quantify the degree of dissociation in the putamen using only the ON condition scans, Putamen-to-thalamus Hyper-perfusion/hypo-metabolism Index (PHI), which may have the potential to be used as a biomarker for LID (correctly classifying 8 out 10 patients). For wider use of PHI, a larger validation study is warranted.

Improvement of the spatial resolution of the MicroPET R4 scanner by wobbling the bed.

The MicroPET R4 scanner was designed for imaging small rodents such as mice and rats. In many cases the spatial resolution of this system is not sufficient for resolving structures of interest. In order to improve the spatial resolution of the MicroPET R4 through improved spatial sampling, the authors have implemented a variable radius eccentric motion, commonly referred to as wobbling, which is applied to the animal bed during scanning. The wobble motion is incorporated into the sinograms using modified histogramming software, capable of reading the bed wobble position from the list-mode data. The histogramming software corrects the data for the dwell time, apparent crystal location, and crystal-pair efficiency and applies a resolution matching filter. The data acquisition, reconstruction, and image display programs provided from the manufacturer required no modifications. For all studies a wobble period of 8 s was used. The optimal wobble radius was found to be 1.50 mm. The wobbled bed acquisition technique was tested by scanning a resolution phantom and a rat. Images from both studies acquired when using the wobble motion showed an improved spatial resolution when compared with comparable images acquired without the wobble motion. The bed wobbling mechanism can be added to any MicroPET system without major changes and without compromising any imaging modes. Implementing the wobble mechanism may represent a cost-effective method to upgrade the spatial resolution of a MicroPET when compared to the purchase of a newer generation system.