Walk-through flat panel total-body PET: a patient-centered design for high throughput imaging at lower cost using DOI-capable high-resolution monolithic detectors.

PURPOSE Long axial field-of-view (LAFOV) systems have a much higher sensitivity than standard axial field-of-view (SAFOV) PET systems for imaging the torso or full body, which allows faster and/or lower dose imaging. Despite its very high sensitivity, current total-body PET (TB-PET) throughput is limited by patient handling (positioning on the bed) and often a shortage of available personnel. This factor, combined with high system costs, makes it hard to justify the implementation of these systems for many academic and nearly all routine nuclear medicine departments. We, therefore, propose a novel, cost-effective, dual flat panel TB-PET system for patients in upright standing positions to avoid the time-consuming positioning on a PET-CT table; the walk-through (WT) TB-PET. We describe a patient-centered, flat panel PET design that offers very efficient patient throughput and uses monolithic detectors (with BGO or LYSO) with depth-of-interaction (DOI) capabilities and high intrinsic spatial resolution. We compare system sensitivity, component costs, and patient throughput of the proposed WT-TB-PET to a SAFOV (= 26 cm) and a LAFOV (= 106 cm) LSO PET systems. METHODS Patient width, height (= top head to start of thighs) and depth (= distance from the bed to front of patient) were derived from 40 randomly selected PET-CT scans to define the design dimensions of the WT-TB-PET. We compare this new PET system to the commercially available Siemens Biograph Vision 600 (SAFOV) and Siemens Quadra (LAFOV) PET-CT in terms of component costs, system sensitivity, and patient throughput. System cost comparison was based on estimating the cost of the two main components in the PET system (Silicon Photomultipliers (SiPMs) and scintillators). Sensitivity values were determined using Gate Monte Carlo simulations. Patient throughput times (including CT and scout scan, patient positioning on bed and transfer) were recorded for 1 day on a Siemens Vision 600 PET. These timing values were then used to estimate the expected patient throughput (assuming an equal patient radiotracer injected activity to patients and considering differences in system sensitivity and time-of-flight information) for WT-TB-PET, SAFOV and LAFOV PET. RESULTS The WT-TB-PET is composed of two flat panels; each is 70 cm wide and 106 cm high, with a 50-cm gap between both panels. These design dimensions were justified by the patient sizes measured from the 40 random PET-CT scans. Each panel consists of 14 × 20 monolithic BGO detector blocks that are 50 × 50 × 16 mm in size and are coupled to a readout with 6 × 6 mm SiPMs arrays. For the WT-TB-PET, the detector surface is reduced by a factor of 1.9 and the scintillator volume by a factor of 2.2 compared to LAFOV PET systems, while demonstrating comparable sensitivity and much better uniform spatial resolution (< 2 mm in all directions over the FOV). The estimated component cost for the WT-TB-PET is 3.3 × lower than that of a 106 cm LAFOV system and only 20% higher than the PET component costs of a SAFOV. The estimated maximum number of patients scanned on a standard 8-h working day increases from 28 (for SAFOV) to 53-60 (for LAFOV in limited/full acceptance) to 87 (for the WT-TB-PET). By scanning faster (more patients), the amount of ordered activity per patient can be reduced drastically: the WT-TB-PET requires 66% less ordered activity per patient than a SAFOV. CONCLUSIONS We propose a monolithic BGO or LYSO-based WT-TB-PET system with DOI measurements that departs from the classical patient positioning on a table and allows patients to stand upright between two flat panels. The WT-TB-PET system provides a solution to achieve a much lower cost TB-PET approaching the cost of a SAFOV system. High patient throughput is increased by fast patient positioning between two vertical flat panel detectors of high sensitivity. High spatial resolution (< 2 mm) uniform over the FOV is obtained by using DOI-capable monolithic scintillators

Twist1 Suppresses Senescence Programs and Thereby Accelerates and Maintains Mutant Kras-Induced Lung Tumorigenesis

KRAS mutant lung cancers are generally refractory to chemotherapy as well targeted agents. To date, the identification of drugs to therapeutically inhibit K-RAS have been unsuccessful, suggesting that other approaches are required. We demonstrate in both a novel transgenic mutant Kras lung cancer mouse model and in human lung tumors that the inhibition of Twist1 restores a senescence program inducing the loss of a neoplastic phenotype. The Twist1 gene encodes for a transcription factor that is essential during embryogenesis. Twist1 has been suggested to play an important role during tumor progression. However, there is no in vivo evidence that Twist1 plays a role in autochthonous tumorigenesis. Through two novel transgenic mouse models, we show that Twist1 cooperates with KrasG12D to markedly accelerate lung tumorigenesis by abrogating cellular senescence programs and promoting the progression from benign adenomas to adenocarcinomas. Moreover, the suppression of Twist1 to physiological levels is sufficient to cause Kras mutant lung tumors to undergo senescence and lose their neoplastic features. Finally, we analyzed more than 500 human tumors to demonstrate that TWIST1 is frequently overexpressed in primary human lung tumors. The suppression of TWIST1 in human lung cancer cells also induced cellular senescence. Hence, TWIST1 is a critical regulator of cellular senescence programs, and the suppression of TWIST1 in human tumors may be an effective example of pro-senescence therapy

Contribution of positron emission tomography in pleural disease.

INTRODUCTION: Positron emission tomography (PET) now plays a clear role in oncology, especially in chest tumours. We discuss the value of metabolic imaging in characterising pleural pathology in the light of our own experience and review the literature. BACKGROUND: PET is particularly useful in characterising malignant pleural pathologies and is a factor of prognosis in mesothelioma. Metabolic imaging also provides clinical information for staging lung cancer, in researching the primary tumour in metastatic pleurisy and in monitoring chronic or recurrent pleural pathologies. CONCLUSIONS: PET should therefore be considered as a useful tool in the diagnosis of liquid or solid pleural pathologies

The Influence of Fetal and Postnatal Growth on Heart Rate Variability in Young Infants

Heart rate variability (HRV), a measure of cardiac autonomic control, was analyzed in infants to assess the hypothesis that early undernutrition may induce autonomic dysfunction that could play a role in the programming of later cardiovascular disease. HRV data were collected during a night session in 546 healthy infants at 5-12 weeks of adjusted age, and statistical associations with fetal and postnatal growth indices were established. A significant positive correlation between birth weight, the ratio of neonatal weight to head circumference and postnatal weight gain, and HRV indices mostly influenced by sympathetic activity was demonstrated in 11- and 12-week-old infants. A slight correlation (p > 0.05) was also found in younger infants. These data suggest the influence of fetal and postnatal growth on the programming of the autonomic nervous system beyond the neonatal period. This influence may be one of the important mechanisms that link impaired growth in fetal and infant life to high blood pressure and other cardiovascular disease during childhood and adulthood (the Barker hypothesis)

Dependency of Premature Ventricular Contractions on Heart Rate and Circadian Rhythms During Childhood

The aim of the present study was to identify and quantify the rate dependence of premature ventricular contractions (PVC) during childhood. A 24-hour Holter recording was performed in 16 consecutive children, aged 22 days to 11 years (mean age 5.6 years), with frequent (>5,000/day), isolated monomorphic PVC. Those PVC were identified and the length of the preceding sinus cycle was measured. The values were ordered into 50-ms class intervals, and the percentage of PVC for each class was calculated and then analyzed by linear regression analysis. On the basis of the significance of the p value, and the positive or negative value of the slope, we identified a tachycardia-enhanced, a bradycardia-enhanced, and an indifferent pattern. Chronobiologic analysis was made by the cosinor method. All the patients had upper and lower limits of cycle length beyond which PVC disappeared. A tachycardia-enhanced pattern was present in 7 patients and an indifferent one in 9 patients. In the latter a second-degree polynomial correlation was systematically found. Children but not infants had a significant circadian variation in the frequency of PVC with a very variable time of highest incidence. In conclusion, it is possible to identify a circadian rhythm of PVC and a spontaneous trend between their incidence and the length of the preceding cardiac cycle in children

Circadian Rhythm of Heart Rate and Heart Rate Variability

BACKGROUND: Measurements of heart rate variability (HRV) are increasingly used as markers of cardiac autonomic activity. AIM: To examine circadian variation in heart rate and HRV in children. SUBJECTS: A total of 57 healthy infants and children, aged 2 months to 15 years, underwent ambulatory 24 hour Holter recording. Monitoring was also performed on five teenagers with diabetes mellitus and subclinical vagal neuropathy in order to identify the origin of the circadian variation in HRV. METHODS: The following variables were determined hourly: mean RR interval, four time domain (SDNN, SDNNi, rMSSD, and pNN50) and four frequency domain indices (very low, low and high frequency indices, low to high frequency ratio). A chronobiological analysis was made by cosinor method for each variable. RESULTS: A significant circadian variation in heart rate and HRV was present from late infancy or early childhood, characterised by a rise during sleep, except for the low to high frequency ratio that increased during daytime. The appearance of these circadian rhythms was associated with sleep maturation. Time of peak variability did not depend on age. Circadian variation was normal in patients with diabetes mellitus. CONCLUSION: We have identified a circadian rhythm of heart rate and HRV in infants and children. Our data confirm a progressive maturation of the autonomic nervous system and support the hypothesis that the organisation of sleep, associated with sympathetic withdrawal, is responsible for these rhythms