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The purpose of this study was to investigate in vivo verification of radiation treatment with high energy photon beams using PET/CT to image the induced positron activity. The measurements of the positron activation induced in a preoperative rectal cancer patient and a prostate cancer patient following 50 MV photon treatments are presented. A total dose of 5 and 8 Gy, respectively, were delivered to the tumors. Imaging was performed with a 64-slice PET/CT scanner for 30 min, starting 7 min after the end of the treatment. The CT volume from the PET/CT and the treatment planning CT were coregistered by matching anatomical reference points in the patient. The treatment delivery was imaged in vivo based on the distribution of the induced positron emitters produced by photonuclear reactions in tissue mapped on to the associated dose distribution of the treatment plan. The results showed that spatial distribution of induced activity in both patients agreed well with the delivered beam portals of the treatment plans in the entrance subcutaneous fat regions but less so in blood and oxygen rich soft tissues. For the preoperative rectal cancer patient however, a 2 ± (0.5) cm misalignment was observed in the cranial-caudal direction of the patient between the induced activity distribution and treatment plan, indicating a beam patient setup error. No misalignment of this kind was seen in the prostate cancer patient. However, due to a fast patient setup error in the PET/CT scanner a slight mis-position of the patient in the PET/CT was observed in all three planes, resulting in a deformed activity distribution compared to the treatment plan. The present study indicates that the induced positron emitters by high energy photon beams can be measured quite accurately using PET imaging of subcutaneous fat to allow portal verification of the delivered treatment beams. Measurement of the induced activity in the patient 7 min after receiving 5 Gy involved count rates which were about 20 times lower than that of a patient undergoing standard (18)F-FDG treatment. When using a combination of short lived nuclides such as (15)O (half-life: 2 min) and (11)C (half-life: 20 min) with low activity it is not optimal to use clinical reconstruction protocols. Thus, it might be desirable to further optimize reconstruction parameters as well as to address hardware improvements in realizing in vivo treatment verification with PET/CT in the future. A significant improvement with regard to (15)O imaging could also be expected by having the PET/CT unit located close to the radiation treatment room.

Background: The purpose of this work was to reveal the research interest value of positron emission tomography (PET) imaging in visualizing the induced tissue activity post high-energy photon radiation treatment. More specifically, the focus was on the possibility of retrieving data such as tissue composition and physical half-lives from dynamic PET acquisitions, as positron-emitting radionuclides such as 15O, 11C, and 13N are produced in vivo during radiation treatment with high-energy photons (>15 MeV). The type, amount, and distribution of induced positron-emitting radionuclides depend on the irradiated tissue cross section, the photon spectrum, and the possible perfusion-driven washout., Methods: A 62-year-old man diagnosed with prostate cancer was referred for palliative radiation treatment of the pelvis minor. A total dose of 8 Gy was given using high-energy photon beams (50 MV) with a racetrack microtron, and 7 min after the end of irradiation, the patient was positioned in a PET/computed tomography (CT) camera, and a list-mode acquisition was performed for 30 min. Two volumes of interests (VOIs) were positioned on the dynamic PET/CT images, one in the urinary bladder and the other in the subcutaneous fat. Analysis of the measured relative count rate was performed in order to compute the tissue compositions and physical half-lives in the two regions., Results: Dynamic analysis from the two VOIs showed that the decay constants of activated oxygen and carbon could be deduced. Calculation of tissue composition from analyzing the VOI containing subcutaneous fat only moderately agreed with that of the tabulated International Commission on Radiation Units & Measurements (ICRU) data of the adipose tissue. However, the same analysis for the bladder showed a good agreement with that of the tabulated ICRU data., Conclusions: PET can be used in visualizing the induced activity post high-energy photon radiation treatment. Despite the very low count rate in this specific application, wherein 7 min after treatment was about 5% of that of a standard 18F-FDG PET scan, the distribution of activated tissue elements (15O and 11C) could be calculated from the dynamic PET data. One possible future application of this method could possibly be to measure and determine the tumor tissue composition in order to identify any hypoxic or necrotic region, which is information that can be used in the ongoing therapy planning process., Trial Registration: The official name of the trial committee of this study is 'Regionala etikprövningsnämnden i Stockholm' (FE 289, Stockholm, SE-17177, Sweden). The unique identifying number is 2011/1789-31/2.

Purpose: Since the first publications on intensity modulated radiation therapy (IMRT) in the early 1980s almost all efforts have been focused on fairly time consuming dynamic or segmental multileaf collimation. With narrow fast scanned photon beams, the flexibility and accuracy in beam shaping increases, not least in combination with fast penumbra trimming multileaf collimators. Previously, experiments have been performed with full range targets, generating a broad bremsstrahlung beam, in combination with multileaf collimators or material compensators. In the present publication, the first measurements with fast narrow high energy (50 MV) scanned photon beams are presented indicating an interesting performance increase even though some of the hardware used were suboptimal., Methods: Inverse therapy planning was used to calculate optimal scanning patterns to generate dose distributions with interesting properties for fast IMRT. To fully utilize the dose distributional advantages with scanned beams, it is necessary to use narrow high energy beams from a thin bremsstrahlung target and a powerful purging magnet capable of deflecting the transmitted electron beam away from the generated photons onto a dedicated electron collector. During the present measurements the scanning system, purging magnet, and electron collimator in the treatment head of the MM50 racetrack accelerator was used with 3-6 mm thick bremsstrahlung targets of beryllium. The dose distributions were measured with diodes in water and with EDR2 film in PMMA. Monte Carlo simulations with GEANT4 were used to study the influence of the electrons transmitted through the target on the photon pencil beam kernel., Results: The full width at half-maximum (FWHM) of the scanned photon beam was 34 mm measured at isocenter, below 9.5 cm of water, 1 m from the 3 mm Be bremsstrahlung target. To generate a homogeneous dose distribution in a 10 x 10 cm2 field, the authors used a spot matrix of 100 equal intensity beam spots resulting in a uniformity of collimated 80%-20% penumbra of 9 mm at a primary electron energy of 50 MeV. For the more complex cardioid shaped dose distribution, they used 270 spots, which at a pulse repetition frequency of 200 Hz is completed every 1.36 s., Conclusions: The present measurements indicate that the use of narrow scanned photon beams is a flexible and fast method to deliver advanced intensity modulated beams. Fast scanned photon IMRT should, therefore, be a very interesting modality in the delivery of biologically optimized radiation therapy with the possibility for in vivo treatment verification with PET-CT imaging.

Objectives: Infection during the induction phase of childhood acute lymphoblastic leukemia (ALL) is a major cause of morbidity and mortality. Several studies have indicated that genetically determined low serum levels of mannose-binding lectin (MBL), a component of innate immunity, are associated with increased risk for infections in patients receiving chemotherapy. Thus, these patients have been proposed to be candidates for MBL replacement therapy., Methods: In a population-based cohort of 137 children with ALL treated at a single pediatric hematology-oncology center with an almost identical chemotherapy regimen, we studied the relationship between polymorphisms in the MBL gene (MBL2) and the MBL2 promoter and the risk of infections during the first 50 d of induction therapy., Results: No increased frequency of infection was seen for the children with genotypes encoding serum low levels of MBL. A higher incidence of fever (P < 0.004), infectious events (P = 0.025), days with neutropenia (P < 0.001) and a higher frequency of antimicrobial therapy (P = 0.0007) were seen in the young age group (<2.5 yr) compared with the older age group (> or =2.5 yr), independent of the MBL genotype., Conclusions: MBL deficiency did not influence the frequency of infections in children receiving induction chemotherapy for ALL, not even in the youngest children (<2.5 yr) whom we found to have the highest risk for infections.

Epidemiological data indicate that acute lymphoblastic leukemia (ALL) could be induced by interactions between the immune system and early childhood infections. Mannose-binding lectin (MBL) plays a critical role in the immune response in early childhood before specific immune protection develops. We investigated whether there may be an association between childhood ALL and low-producing MBL genotypes. Serum MBL levels depend on normal (A) or defective (O) alleles, and on normal (Y) or reduced (X) promoter activities. For this study, 137 noninfants with ALL and 250 controls were classified into 3 MBL genotype groups according to their influence on the serum level of functional MBL: group I, YA/YA and YA/XA (higher levels); group II, XA/XA and YA/O (intermediate levels); and group III, MBL insufficiency with XA/O or O/O (MBL-deficient) genotypes. Compared with controls, cases more often had low-level genotypes (I/II/III: 63 [46%]/44 [32%]/30 [22%] vs 145 [58%]/65 [26%]/40 [16%]; P =.02) and MBL deficiency (8.8% vs 2.8%; P =.009). Thus, the ALL odds ratio for MBL-deficient versus nondeficient individuals was 3.3 (95% CI, 1.3-8.7), whereas the ALL odds ratio for group I versus group II/III genotypes was 0.62 (95% CI, 0.41-0.94). MBL group III patients were significantly younger at diagnosis than patients in group I/II (median, 3.9 vs 5.2 years; P =.04). The study shows that the presence of low-level MBL genotypes is associated with an increased risk of childhood ALL, particularly with early age at onset.

We reviewed the clinical presentation, subsequent course and outcome of 45 newborn infants with neuotizing enterocolitis (NEC) seen on eight neonatal intensive care units during a 10 year period (01.01.82-31.12.91). The average incidence of NEC was found to be 1.2 (0.3-3.8) per 10,000 liveborn infants with a tendency to increase during the period. Eighteen percent had a birth weight of less than 1,000 g. Thirty-six percent had a birthweight between 1,000 and 1,500 g. Twenty-nine percent had a birthweight between 1,500 and 2,500 g. The last group made up of 16% had birth weights above 2,500 g. The mortality was determined by the severity of the disease, being 0% for infants within Bell's stage I, 25% in Bell's stage II and 71% in Bell's stage III. Sixty-nine percent of the infants were diagnosed in stage III, probably because of low attention to NEC in its early stages. The prognosis of surviving infants was good with no gastrointestinal symptoms when evaluated four to five years later.

Concentrations of prolactin in amniotic fluid, fetal plasma, and maternal plasma were determined in 34 rhesus monkeys delivered by hysterotomy under general anesthesia at gestational ages of 110 to 160 days (term, 165 days). Included were 15 cases (gestational ages 110 to 143 days) in which the mothers received 2 mg of betamethasone intramuscularly daily for 3 days prior to delivery. Fetal lung maximum volumes were determined in addition to the following indices of fetal lung surfactant: lung alveolar stability, lung phosphatidylcholine concentrations, lung extract surface tensions, and amniotic fluid lecithin to sphingomyelin ratios. Amniotic fluid prolactin was found to correlate significantly with lung alveolar stability (r = 0.51; p less than 0.01), lung phosphatidylcholine (r = 0.51; p less than 0.01), lung extract surface tension (r = -0.39, p less than 0.05) and amniotic fluid lecithin/sphingomyelin ratio (r = 0.50; p less than 0.01). These correlations remained statistically significant even when the effects of gestational age were taken into account. These findings suggest that amniotic fluid may modulate fetal production of surfactant via its prolactin content.

A study was made of ovaries perfused in vitro with a liquid fluorocarbon that was stabilized in emulsion by a nonionic detergent to which tissue culture medium was added. A pulsatile flow was used in an organ preservation system under aseptic conditions. Glucose was utilized and lactate produced at a fairly constant rate for as long as 20 hours of perfusion. 14-C-progesterone and 14-C-17alphaOH-progesterone were synthesized from 14-C-acetate and estradiol was secreted. The production of these steroids by the perfused ovary appears to be responsive to gonadotropins.

Alterations in plasma prolactin (PRL) concentrations in response to nursing in puerperally lactating women are often significant beyond the 90th postpartum day, yet the increment appears unrelated to the frequency or duration of the nursing stimulus. Tonic gonadotropin secretion is low, assuming a more episodic secretory pattern either when the frequency of breast-feeding is reduced or when weaning takes place. Significant increments in peripheral concentrations of luteinizing hormone can be seen in response to weaning coincident with a fall in peripheral plasma PRL concentration. At the same time, peripheral estrogen concentrations increase, suggesting that a specific set point for ovarian responsiveness to gonadotropins exists. Whether this set point is related solely to the peripheral concentration of gonadotropins or whether it is also related to the peripheral PRL concentration is not known at this time.