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Effective positron emission tomography / computed tomography (PET/CT) guidance in radiotherapy of lung cancer requires estimation and mitigation of errors due to respiratory motion. An end-to-end workflow was developed to measure patient-specific motion-induced uncertainties in imaging, treatment planning, and radiation delivery with respiratory motion phantoms and dosimeters. A custom torso phantom with inserts mimicking normal lung tissue and lung lesion was filled with [(18)F]FDG. The lung lesion insert was driven by six different patient-specific respiratory patterns or kept stationary. PET/CT images were acquired under motionless ground truth, tidal breathing motion-averaged (3D), and respiratory phase-correlated (4D) conditions. Target volumes were estimated by standardized uptake value (SUV) thresholds that accurately defined the ground-truth lesion volume. Non-uniform dose-painting plans using volumetrically modulated arc therapy were optimized for fixed normal lung and spinal cord objectives and variable PET-based target objectives. Resulting plans were delivered to a cylindrical diode array at rest, in motion on a platform driven by the same respiratory patterns (3D), or motion-compensated by a robotic couch with an infrared camera tracking system (4D). Errors were estimated relative to the static ground truth condition for mean target-to-background (T/Bmean) ratios, target volumes, planned equivalent uniform target doses, and 2%-2 mm gamma delivery passing rates. Relative to motionless ground truth conditions, PET/CT imaging errors were on the order of 10-20%, treatment planning errors were 5-10%, and treatment delivery errors were 5-30% without motion compensation. Errors from residual motion following compensation methods were reduced to 5-10% in PET/CT imaging, <5% in treatment planning, and <2% in treatment delivery. We have demonstrated that estimation of respiratory motion uncertainty and its propagation from PET/CT imaging to RT planning, and RT delivery under a dose painting paradigm is feasible within an integrated respiratory motion phantom workflow. For a limited set of cases, the magnitude of errors was comparable during PET/CT imaging and treatment delivery without motion compensation. Errors were moderately mitigated during PET/CT imaging and significantly mitigated during RT delivery with motion compensation. This dynamic motion phantom end-to-end workflow provides a method for quality assurance of 4D PET/CT-guided radiotherapy, including evaluation of respiratory motion compensation methods during imaging and treatment delivery.

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BACKGROUND: Infants conceived from IVF are at increased risk for low birthweight. Animal studies suggest that embryo culture medium influences birthweight but it is unknown whether this association exists in humans. This study examines the relationship between culture medium and birthweight following IVF. METHODS: We identified all IVF cycles with start dates between 1 January 1999 and 31 December 2008 that used autologous oocytes with resulting embryos cultured in G1.3, Global or G1.5 medium. The population was restricted to singleton deliveries following Day 3, fresh single embryo transfer, or twin deliveries following Day 3, fresh double embryo transfer, at a gestational age of ≥ 34 weeks. Only the first cycle during the study period was included for each woman. Women were excluded if the number of gestational sacs on ultrasound differed from the number of infants born. Variables were evaluated with the χ²-test or analysis of variance. Multiple linear regressions controlled for potential confounders. RESULTS: Of the 198 women with singleton deliveries, 102 embryos were cultured in G1.3, 53 in Global and 43 in G1.5 medium. Of the 303 twin deliveries, 172 pairs of embryos were cultured in G1.3, 58 in Global and 73 in G1.5 medium. No significant association between culture medium and birthweight was observed, even when controlling for potential confounders. CONCLUSIONS: This retrospective study demonstrated no significant association between embryo culture medium and birthweight following IVF. Although our careful selection of patients minimized the influence of potential confounders, further research is required to elucidate this issue with larger numbers of patients.

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PURPOSE: In this study, the authors validated a novel respiratory tracking device, the multidimensional respiratory tracking (MDRT) system, that was designed to assist in correcting for respiratory motion in PET/CT images. The authors also investigated a novel PET acquisition technique, smart gating (SG), that enables to acquire motion-free PET data prospectively, with minimum user interference and with no additional postprocessing of the PET data. METHODS: MDRT uses visual tracking techniques to track simultaneously the two-dimensional (in the vertical plane) motion of multiple fiducial markers using a standard video camera. A threshold window is set at the breathing amplitude of interest using the MDRT GUI. A trigger is generated at a rate of 250 Hz as long as the breathing signal is within the threshold window. The triggers are fed into the PET scanner to initialize one single bin of a gated acquisition every 4 ms. No triggers are delivered as the breathing signal drifts outside the threshold window. Consequently, PET data are acquired only whenever the breathing signal is confined within the amplitude threshold window, thus resulting into a motion-free image set. The accuracy of MDRT in tracking the breathing signal was assessed (1) by comparing the period of an oscillating phantom, as measured by MDRT, to that measured with a photogate timer and (2) by comparing the MDRT output to that of the real-time position management (RPM) in ten patients. The SG PET/CT acquisition was validated in phantoms and in two stereotactic body radiosurgery (SBRS) lung DIBH-PET/CT patients. RESULTS: MDRT was in agreement with the photogate timer in determining the period of motion to less than 2%. The percent errors between MDRT and RPM in the positions of the peaks and troughs of the ten patients' breathing signals were within 10%. In phantoms, SG technique enables to correct for motion-induced artifacts in the PET images and improve the accuracy of PET quantitation. For the SBRS application, in one patient, the patient's CT lesion was not detected in the corresponding clinical PET images, while it exhibited an SUV of 1.8 in the DIBH image set. In the second patient, DIBH-PET images showed an improved PET-to-CT spatial matching and a 52% increase in the lesion SUV. CONCLUSIONS: MDRT has been shown to be accurate in tracking breathing motion and assisted in implementing a smart-gating PET acquisition technique that allowed to acquire prospectively motion-free PET images.

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We measured count rates and scatter fraction on the Discovery STE PET/CT scanner in conventional 2D and 3D acquisition modes, and in a partial collimation mode between 2D and 3D. As part of the evaluation of using partial collimation, we estimated global count rates using a scanner model that combined computer simulations with an empirical live-time function. Our measurements followed the NEMA NU2 count rate and scatter-fraction protocol to obtain true, scattered and random coincidence events, from which noise equivalent count (NEC) rates were calculated. The effect of patient size was considered by using 27 cm and 35 cm diameter phantoms, in addition to the standard 20 cm diameter cylindrical count-rate phantom. Using the scanner model, we evaluated two partial collimation cases: removing half of the septa (2.5D) and removing two-thirds of the septa (2.7D). Based on predictions of the model, a 2.7D collimator was constructed. Count rates and scatter fractions were then measured in 2D, 2.7D and 3D. The scanner model predicted relative NEC variation with activity, as confirmed by measurements. The measured 2.7D NEC was equal or greater than 3D NEC for all activity levels in the 27 cm and 35 cm phantoms. In the 20 cm phantom, 3D NEC was somewhat higher ( approximately 15%) than 2.7D NEC at 100 MBq. For all higher activity concentrations, 2.7D NEC was greater and peaked 26% above the 3D peak NEC. The peak NEC in 2.7D mode occurred at approximately 425 MBq, and was 26-50% greater than the peak 3D NEC, depending on object size. NEC in 2D was considerably lower, except at relatively high activity concentrations. Partial collimation shows promise for improved noise equivalent count rates in clinical imaging without altering other detector parameters.

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A current theory of attention deficit/hyperactivity disorder (ADHD) implicates a dysfunction in working memory as a significant factor in ADHD. The Working Memory Indexes of the Wechsler Adult Intelligence Scale--Third Edition (WAIS-III; The Psychological Corporation, 1997a) and the Wechsler Memory Scale--Third Edition (WMS-III; The Psychological Corp -oration, 1997b) were used to evaluate this theory. Seventy adults clinically diagnosed with ADHD (mean age = 25) and who were previously administered the WAIS-III and WMS-III were reviewed to determine the association between working memory and ADHD symptomology. The respondent was asked to estimate the frequency of occurrence of ADHD symptoms by completing the Brown ADD Scales (Brown, 1996). Results indicated no significant relationship between working memory and self-reported symptoms, although the Working Memory Indexes of the WAIS-III and the WMS-III were significantly correlated. Implications for current ADHD theory and suggestions for future research were discussed.

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Hodgkin's disease (HD), which affects all age groups, has been associated with childhood social class, particularly among adults under age 40. Little is known about social class risk factors in older adults, and the few existing studies have conflicting findings. As part of a population-based case-control study of HD in women, we examined social class risk factors by diagnostic age groups (45-54 years and 55-79 years) corresponding to incidence patterns and by histologic subtypes based on a uniform pathologic review. Among women ages 45-54, cases were more likely to be Catholic, to have lower income and to be taller than controls. Among women ages 55-79, cases tended to have come from small or large childhood households, lived in single-family childhood housing, and had a single rather than shared bedroom at age 11. For the nodular sclerosis (NS) histologic subtype, similar age differences in risk factors were apparent. Comparisons between the NS and non-NS subtypes in women ages 55-79 identified some common risk factors (single-family childhood home, single bedroom at age 11) but others specific to one subtype (childhood household size, adult height for NS; lower maternal education for non-NS). Thus, some social class associations with HD differed between middle-aged and older women, as well as between these groups and younger adults, while others were shared across age groups. Risk also was associated with both higher and lower childhood social class in middle-aged and older women, in contrast with previous findings. None of these patterns was explained entirely by histologic subtype but may reflect age and histology subtype variation in the HD-EBV association.

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Robert Falcon Scott and his companions reached the South Pole in January of 1912, only to die on their return journey at a remote site on the Ross Ice Shelf, about 170 miles from their base camp on the coast. Numerous contributing causes for their deaths have been proposed, but it has been assumed that the cold temperatures they reported encountering on the Ross Ice Shelf, near 82-80 degrees S during their northward trek toward safety, were not unusual. The weather in the region where they perished on their unassisted trek by foot from the Pole remained undocumented for more than half a century, but it has now been monitored by multiple automated weather stations for more than a decade. The data recorded by Scott and his men from late February to March 19, 1912, display daily temperature minima that were on average 10 to 20 degrees F below those obtained in the same region and season since routine modern observations began in 1985. Only 1 year in the available 15 years of measurements from the location where Scott and his men perished displays persistent cold temperatures at this time of year close to those reported in 1912. These remarkably cold temperatures likely contributed substantially to the exhaustion and frostbite Scott and his companions endured, and their deaths were therefore due, at least in part, to the unusual weather conditions they endured during their cold march across the Ross Ice Shelf of Antarctica.

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Several authors have evaluated consonant-to-vowel ratio (CVR) enhancement as a means to improve speech recognition in listeners with hearing impairment, with the intention of incorporating this approach into emerging amplification technology. Unfortunately, most previous studies have enhanced CVRs by increasing consonant energy, thus possibly confounding CVR effects with consonant audibility. In this study, we held consonant audibility constant by reducing vowel transition and steady-state energy rather than increasing consonant energy. Performance-by-intensity (PI) functions were obtained for recognition of voiceless stop consonants (/p/, /t/, /k/) presented in isolation (burst and aspiration digitally separated from the vowel) and for consonant-vowel syllables, with readdition of the vowel /a/. There were three CVR conditions: normal CVR, vowel reduction by 6 dB, and vowel reduction by 12 dB. Testing was conducted in broadband noise fixed at 70 dB SPL and at 85 dB SPL. Six adults with sensorineural hearing impairment and 2 adults with normal hearing served as listeners. Results indicated that CVR enhancement did not improve identification performance when consonant audibility was held constant, except at the higher noise level for one listener with hearing impairment. The re-addition of the vowel energy to the isolated consonant did, however, produce large and significant improvements in phoneme identification.

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We investigated the contractile effects of both activated and unactivated polymorphonuclear leukocytes (PMNs) on human vascular tissue to characterize the influence of human PMNs on vascular tone. PMNs were added either unactivated or after f-met-leu-phe (fMLP) activation (10(-8) M), into tissue chambers containing human umbilical vein segments under either control or cytokine-treated conditions. The activation state of different PMN preparations was measured by immunofluorescence staining of the adhesion glycoproteins Mac-1 and L-selectin. Both unactivated and activated PMNs induced a cell number-dependent (1.5 x 10(5) to 2 x 10(6) cells/ml) vasoconstriction in human umbilical vein segments. This PMN-induced response was not inhibited by treatment with indomethacin (10(-5) M), superoxide dismutase (2 x 10(-7) M) or L-nitro-monomethyl arginine (10(-4) M). However, treatment of PMNs with the leukotriene biosynthesis inhibitor BIRM-270 partially inhibited (-61 +/- 19%, P <.05) the contraction induced only by unactivated PMNs. Moreover, the supernatant from unactivated, but not that from activated, PMNs elicited a contractile response comparable to that from the addition of cells. We observed a significant correlation between the Mac-1/L-selectin ratio of activated PMNs and the contractile response they generated (r = 0.77, P <.05). The activated PMN response had an endothelium-dependent component, whereas the unactivated PMN response was endothelium-independent. These results suggest that human PMNs of varying activation states have the capacity to modulate vascular smooth muscle tone via distinct mechanisms. Unactivated PMNs appear to modulate tone via a secreted product, whereas the more activated phenotype modulates vascular tone via a cognate interaction with the endothelium.

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CD26 and ecto-adenosine deaminase (ADA) are found associated on the plasma membrane of T lymphocytes and each possess distinct catalytic activities. CD26 has a proteolytic activity identical to dipeptidylpeptidase IV (DPPIV; E.C. 3.4.14.5), and ecto-ADA (E.C. 3.5.4.4) degrades extracellular adenosine. The cell surface expression of CD26 and ecto-adenosine deaminase (ecto-ADA) is regulated on stimulated T lymphocytes, and ADA binding to CD26 produces a synergistic costimulatory response with T cell receptor activation. This study addresses the potential regulation by allosteric interactions of the catalytic activities of CD26 associated with ecto-ADA, which could define the mechanism of the synergism observed in T cell signaling. Cell lines genetically deficient in ADA, ligands for ADA such as adenosine, and a specific inhibitor of ADA, deoxycoformycin, were used to define the effect of ADA activity on CD26 DPPIV activity and affinity for dipeptide substrate. Conversely, a recombinant Chinese hamster ovary cell line expressing human CD26 with or without a mutation in the DPPIV catalytic domain, and the boronic acid inhibitor Val-boroPro, were used to determine the effect of DPPIV activity on ecto-ADA activity and association with CD26. These studies found no significant allosteric interaction between the catalytic activities of CD26 and ecto-ADA when associated. Therefore, signaling events in T cells involving costimulation with CD26 and ecto-ADA and the synergism observed upon ADA binding to CD26 occur independently of the catalytic activities of these cell surface molecules.

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METHODS: This study characterizes the performance of a newly developed whole-body PET scanner (Advance, General Electric Medical Systems, Milwaukee, WI). The scanner consists of 12,096 bismuth germinate crystals (4.0 mm transaxial by 8.1 mm axial by 30 mm radial) in 18 rings, giving 35 two-dimensional image planes through an axial field of view of 15.2 cm. The rings are separated by retractable tungsten septa. Intrinsic spatial resolution, scatter fraction, sensitivity, high count rate performance and image quality are evaluated. RESULTS: Transaxial resolution (in FWHM) is 3.8 mm at the center and increases to 5.0 mm tangential and 7.3 mm radial at R = 20 cm. Average axial resolution decreases from 4.0 mm FWHM at the center to 6.6 mm at R = 20 cm. Scatter fraction is 9.4% and 10.2% for direct and cross slices, respectively. With septa out, the average scatter fraction is 34%. Total system sensitivity for true events (in kcps/(microCi/cc)) is 223 with septa in and 1200 with septa out. Dead-time losses of 50% correspond to a radioactivity concentration of 4.9 (0.81) microCi/cc and a true event count rate of 489 (480) kcps with septa in (out). Noise-equivalent count rate (NECR) for the system as a whole shows a maximum of 261 (159) kcps at a radioactivity concentration of 4.1 (0.65) microCi/cc with septa in (out). NECR is insensitive to changes in lower gamma-energy discrimination between 250-350 keV. CONCLUSIONS: The results show the performance of the newly designed PET scanner to be well suited for clinical and research applications.

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Three-dimensional filtered backprojection uses filters generally specified in the Fourier domain. Implementing these filters by direct sampling in the Fourier domain produces an artifact in the reconstructed images consisting primarily of a DC shift. This artifact is caused by aliasing of the reconstruction filter. We have developed a filter construction technique using Fourier domain oversampling, which reduces the artifact. A method to construct the filter efficiently without the need to create and store the entire oversampled filter array is also presented. Quantitative accuracy in filtered backprojection is of particular importance in multiple-pass algorithms used to reconstruct data from cylindrical PET scanners. We are able to implement such algorithms without fitting the reprojected views to the scanner data.

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Activated Th cells deliver contact-dependent signals to resting B lymphocytes that initiate and drive B cell proliferation. Recently, a ligand for the B lymphocyte membrane protein, CD40, has been identified that delivers contact-dependent Th cell signals to B cells. A dimeric soluble form of CD40 was produced and used to further characterize the regulation of expression of the CD40 ligand. Expression of the CD40 ligand was rapidly induced after Th lymphocyte activation, and its stability depended upon whether Th cells were activated with soluble or plastic-bound stimuli. Th cells activated with soluble stimuli rapidly turned over cell-surface CD40 ligand whereas Th cells activated with plastic-bound stimuli exhibited more stable CD40 ligand expression for up to 48 h. Removal of activated Th cells from the plastic-bound stimulus resulted in a rapid turnover of CD40 ligand, suggesting that continuous stimulation could maintain CD40 ligand expression. Ligation by soluble CD40 could also stabilize expression of CD40 ligand on the Th cell surface. Both CD40 ligand and IL-2 were transiently synthesized from 1 to 12 h after Th cell activation and had similar kinetics of synthesis. In Con A-activated Th cells newly synthesized CD40 ligand exhibited an initial high turnover (1.5 h t1/2) and after 5 h of Th cell activation became more stable (10-h t1/2). In Th cells activated with plastic-bound anti-CD3, CD40 ligand exhibited a similar biphasic turnover except that the rapid turnover phase began significantly later. This delay could allow more time for newly synthesized CD40 ligand to assemble or associate with other molecules and thus become stabilized on the cell surface. Newly synthesized CD40 ligand in Con A-activated Th cells appeared to not be efficient in delivering Th cell-dependent contact signals to resting B cells, implying the need for assembly or accessory proteins. Regulation of CD40 ligand expression was consistent with all the characteristics of Th cell-delivered contact signals to B cells and may contribute to the high degree of specificity in B cell responses.

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Noise equivalent counts are a convenient and effective means to assess PET emission image quality. The method is extended to include the effects of transmission imaging on the statistics of attenuation corrected PET data. The result of the calculations is a noise figure which describes the SNR performance of the elements of the attenuation corrected emission sinogram. The noise figure demonstrates the tradeoff between emission and transmissions imaging performance, and can be used to determine optimal partitioning of imaging time between emission and transmission scans. Also, the technique can be used to compare the efficacy of simultaneous transmission/emission imaging techniques and multiple orbiting rod source geometries. Experimental and simulated results from the GE 2048 PET scanner are used to demonstrate the model. In a sample imaging situation in that system geometry, the dual rod source achieves 80% of the noise figure improvement which is available in simultaneous transmission/emission imaging without transmission data filtering, and demonstrates superior performance when a 3-point averaging transmission filter is applied.

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Aerosol ovalbumin challenge (OA) of sensitized guinea pigs induced airway hyperreactivity (AH) to i.v. acetylcholine (Ach) and serotonin (5-HT) 24 hr post OA. Bronchoalveolar lavage fluid 24 hrs after OA showed increased leukocytes compared to unsensitized unchallenged animals. Treatment with monoclonal antibody R15.7 (3 mg/kg i.v.,) 1 hr prior and 4 hours after OA prevented the induction of AH to Ach but not to 5-HT and reduced influx of leukocytes. We conclude: 1) antigen inhalation induces an increase in AH with an increase in proinflammatory cell influx and 2) treatment with anti-CD18 antibody inhibits cell influx and airway hyperreactivity.

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