Is there an ideal set of prospective scan acquisition phases for fast-helical based 4D-CT?

The article aims to determine if a prospective acquisition algorithm can be used to find the ideal set of free-breathing phases for fast-helical model-based 4D-CT. A retrospective five-patient dataset that consisted of 25 repeated free breathing CT scans per patient was used. The sum of the square root amplitude difference between all the breathing phases was defined as an objective function to determine the optimality of sets of breathing phases. The objective function was intended to determine if a specific set of breathing phases would yield a motion model that could accurately predict the motion in all 25 CT scans. Voxel specific motion models were calculated using all combinations of N scans from 25 breathing trajectories, (3 ⩽ N ⩽ 25), and the minimum number of scans required to absolutely characterize the motion model was analyzed. This analysis suggests that the number of scans could potentially be reduced to as few as five scans. When the objective function was large, the resulting motion model provided an excellent approximation to the motion model created using all 25 scans.

Proton pencil beam scanning for mediastinal lymphoma: the impact of interplay between target motion and beam scanning.

The purpose of this study was to assess the feasibility of proton pencil beam scanning (PBS) for the treatment of mediastinal lymphoma. A group of 7 patients of varying tumor size (100-800 cc) were planned using a PBS anterior field. We investigated 17 fractions of 1.8 Gy(RBE) to deliver 30.6 Gy(RBE) to the internal target volume (ITV). Spots with σ ranging from 4 mm to 8 mm were used for all patients, while larger spots (σ = 6-16 mm) were employed for patients with motion perpendicular to the beam (⩾5 mm), based on initial 4-dimensional computed tomography (4D CT) motion evaluation. We considered volumetric repainting such that the same field would be delivered twice in each fraction. The ratio of extreme inhalation amplitude and regular tidal inhalation amplitude (free-breathing variability) was quantified as an indicator of potential irregular breathing during the scanning. Four-dimensional dose was calculated on the 4D CT scans based on the respiratory trace and beam delivery sequence, implemented by partitioning the spots into separate plans on each 4D CT phase. Four starting phases (end of inhalation, end of exhalation, middle of inhalation and middle of exhalation) were sampled for each painting and 4 energy switching times (0.5 s, 1 s, 3 s and 5 s) were tested, which resulted in 896 dose distributions for the analyzed cohort. Plan robustness was measured for the target and critical structures in terms of the percent difference between 'delivered' dose (4D-evaluated) and planned dose (calculated on average CT). It was found that none of the patients exhibited highly variable or chaotic breathing patterns. For all patients, the ITV D98% was degraded by <2% (standard deviations âˆ¼ 0.1%) when averaged over the whole treatment course. For six out of seven patients, the average degradation of ITV D98% per fraction was within 5% . For one patient with motion perpendicular to the beam (⩾5 mm), the degradation of ITV D98% per fraction was up to 15%, which was mitigated to 2% by employing larger spots and repainting. Deviation of mean lung dose was at most 0.2 Gy(RBE) (less than 1% of prescribed dose, 30.6 Gy(RBE)), while the deviation of heart maximum dose and cord maximum dose could exceed 5% of the prescribed dose. No significant difference in either target coverage or normal tissue dose was observed for different energy switching times compared via two-sided Wilcoxon signed-rank tests (p < 0.05). This feasibility study demonstrates that, for mediastinal lymphoma, the impact of the interplay effect on the PBS plan robustness is minimal when volumetric repainting and/or larger spots are employed.

Generating lung tumor internal target volumes from 4D-PET maximum intensity projections.

PURPOSE: Positron emission tomography (PET) of lung tumors suffers from breathing-motion induced blurring. Respiratory-correlated PET ameliorates motion blurring and enables visualization of lung tumor functional uptake throughout the breathing cycle but has achieved limited clinical use in radiotherapy planning. In this work, the authors propose a process for generating a gated PET maximum intensity projection (MIP), a breathing-phase projection of the 4D image set comprising gated PET images, as a technique to quantitatively and efficiently incorporate respiratory-correlated PET information into radiotherapy treatment planning. METHODS: 4D-CT and respiratory-gated PET using [(18)F]fluorodeoxyglucose (FDG) were acquired of three patients with a total of four small (4-18 cc), clearly defined lower-lobe lung tumors. Internal target volumes (ITVs) for the lung tumors were generated by threshold-based segmentation of PET-MIP images and ungated PET images (ITV(PET-MIP) and ITV(3D-PET), respectively), and by manual contouring of CT-MIP and end-exhale and end-inhale phases of 4D-CT (ITV(CT-MIP)) by a radiation oncologist. Because of the sensitivity of tumor segmentation to threshold value, several different thresholds were tested for ITV generation, including 40%, 30%, and 20% of maximum standardized uptake value (SUV(max)) for FDG as well as absolute SUV thresholds of 2.5 and 3.0. The normalized overlap and relative volumes of ITV(PET-MIP) and ITV(3D-PET) with respect to ITV(CT-MIP) were compared. The images were also visually compared. ITV(CT-MIP) was considered a gold standard for these tumors with CT-visible morphology. RESULTS: The mean and standard deviation normalized overlap and relative volumes between ITV(PET-MIP) and ITV(CT-MIP) were 0.68 ± 0.07 and 1.07 ± 0.42, respectively, averaged over all four tumors and all five threshold values. The mean and standard deviation normalized overlap and relative volumes of ITV(3D-PET) and ITV(CT-MIP) were 0.47 ± 0.12 and 0.69 ± 0.56, respectively. CONCLUSIONS: PET-MIP images better match CT-MIP images for this sample of four small CT-visible tumors as compared to ungated PET images, based on the metrics of volumetric overlap and relative volumes as well as visual interpretation. The PET-MIP is a way to incorporate 4D-PET imaging into the process of lung tumor contouring that is time-efficient for the radiation oncologist and involves minimal effort to implement in treatment planning software, because it requires only a single PET image beyond contouring on CT alone.

gamma-Linolenic acid treatment of rheumatoid arthritis. A randomized, placebo-controlled trial.

OBJECTIVE: To assess the clinical efficacy and adverse effects of gamma-linolenic acid (GLA), a plant seed oil-derived unsaturated fatty acid that suppresses inflammation and joint tissue injury in animal models, in the treatment of active rheumatoid arthritis (RA). METHODS: Fifty-six patients with active RA were randomized to treatment groups in a 6-month, double-blind trial of GLA versus placebo. This was followed by a 6-month, single-blind trial during which all patients received GLA. Patients were treated with 2.8 gm/day of GLA as the free fatty acid or with sunflower seed oil (placebo) administered in identical capsules. RESULTS: Treatment with GLA for 6 months resulted in statistically significant and clinically relevant reductions in the signs and symptoms of disease activity in patients with RA. Overall meaningful responses (at least 25% improvement in 4 measures) were also better in the GLA treatment group (14 of 22 patients versus 4 of 19 in the placebo group; P = 0.015). During the second 6 months, both groups exhibited improvement in disease activity. Thus, patients taking GLA during the entire study showed progressive improvement during the second 6 months. In this group, 16 of 21 patients showed meaningful improvement at 12 months compared with study entry. CONCLUSION: GLA at doses used in this study is a well-tolerated and effective treatment for active RA. GLA is available as a component of several plant seed oils and is usually taken in far lower doses than were used in this trial. It is not approved in the United States for the treatment of any condition, and should not be viewed as therapy for any disease. Further controlled studies of its in RA are warranted.

Perinatal mortality in the infants of diabetic women.

The causes of 50 perinatal deaths which occurred over an 18-year period in the infants of women with either established (n = 205) or gestational (n = 2,442) diabetes were studied. The perinatal mortality rate in these groups was 5.4% and 1.6% respectively and the causes of deaths were similar in both groups. Intrauterine hypoxia was found to be the commonest cause of death, followed by congenital malformations and respiratory distress syndrome. The implications of these findings for measures to reduce such deaths are discussed.

Aerobic exercise in pregnancy.

The effect on fetal and maternal outcome in gestational exercise in a recreational athlete was investigated in a 2 1/2-year prospective study. A training effect in a pregnant subject engaged in aerobic exercise was also determined. One hundred forty-one low-risk pregnant subjects had their aerobic capacity tested during the first trimester, during the third trimester, and post partum. Predicted maximum oxygen consumption values were determined by using standard Bruce treadmill protocol during the first and third tests and the Astrand protocol for submaximal testing on a bicycle ergometer during the third trimester. Exercise prescriptions were given. The primiparous and multiparous subjects were randomized into control and exercise groups, differing only in the frequency of aerobic exercise. The results showed that exercise had no associated increase in neonatal morbidity and obstetric complications. All subjects improved or maintained their level of aerobic fitness. The exercisers showed a significant training effect. The disparity in the second test's results may suggest that the physiologic characteristics of pregnancy masked the aerobic improvement.

Initiation and control of ovulation in the mouse luteal phases. Effects of oestrogen, progesterone and prolactin.

The aim of the present study was to examine the effect of exogenous oestrogen and progesterone on ovulation in early pregnant mice and at the end of pseudopregnancy. The results demonstrate that there are mature follicles during early pregnancy which were induced to ovulate by administration of large doses of oestrogen (greater than or equal to 10 micrograms) on day 4 of pregnancy. Ovulation was also induced by inhibition of progesterone secretion with bromocriptine. If progesterone or prolactin was given in conjunction with bromocriptine, the ovulation effect was abolished. At the end of pseudopregnancy, the spontaneous ovulation was inhibited by injections of progesterone (1.0 mg). Oestrogen given by itself at the end of pseudopregnancy caused the animals to mate earlier than the control animals. This confirms the presence of mature follicles in mice during pregnancy and suggests that the LH peak needed for ovulation can either be provoked by administration of oestrogen or by blocking of progesterone.

Initiation and control of ovulation in the mouse luteal phases. Effects of gonadotropins and gonadotropin releasing hormone.

The aim of the present study was to examine the induction of ovulation during pregnancy, pseudopregnancy, and suckling-delayed pregnancy in mice using exogenous gonadotropins. The present results demonstrate that there are mature follicles in the ovary which can be induced to ovulate with administration of either exogenous human chorionic gonadotropin (hCG) or luteinizing hormone (LH) during pregnancy (Days 1-12) and pseudopregnancy (Days 4-8) in the mouse. hCG was relatively ineffective in initiating ovulation during suckling-delayed pregnancy, and hCG could not induce ovulation on Days 3-6 in any animals, suggesting that follicular growth is not continuous during suckling-delayed pregnancy in the mouse. Ovulation occurred in pregnant and pseudopregnant mice following injection of gonadotropin releasing hormone (GnRH) in a gelatin delay vehicle. Injection of GnRH in saline did not initiate ovulation in pregnant or pseudopregnant mice. A large release of LH was shown to occur following injection of GnRH in gelatin, but no release occurred after the same dose of GnRH in saline. In conclusion, the experiments demonstrate the existence of mature follicles during murine pregnancy and pseudopregnancy, and the lack of inductable follicles during suckling-delayed pregnancy.