ABSTRACT
BACKGROUND: Air pollution exposure during pregnancy has been associated with numerous adverse pregnancy, birth, and child health outcomes. One proposed mechanism underlying these associations is maternal immune activation and dysregulation. We examined associations between PM2.5 and NO2 exposure during pregnancy and immune markers within immune function groups (TH1, TH2, TH17, Innate/Early Activation, Regulatory, Homeostatic, and Proinflammatory), and examined whether those associations changed across pregnancy. METHODS: In a pregnancy cohort study (n=290) in Rochester, New York, we measured immune markers (using Luminex) in maternal plasma up to 3 times during pregnancy. We estimated ambient PM2.5 and NO2 concentrations at participants' home addresses using a spatial-temporal model. Using mixed effects models, we estimated changes in immune marker concentrations associated with interquartile range increases in PM2.5 (2.88 µg/m3) and NO2 (7.82 ppb) 0 to 6 days before blood collection, and assessed whether associations were different in early, mid, and late pregnancy. RESULTS: Increased NO2 concentrations were associated with higher maternal immune markers, with associations observed across TH1, TH2, TH17, Regulatory, and Homeostatic groups of immune markers. Furthermore, the largest increases in immune markers associated with each 7.82 ppb increase in NO2 concentration were in late pregnancy (e.g., IL-23 = 0.26 pg/ml, 95% CI= 0.07, 0.46) compared to early pregnancy (e.g., IL-23 = 0.08 pg/ml, 95% CI= -0.11, 0.26). CONCLUSIONS: Results were suggestive of NO2-related immune activation. Increases in effect sizes from early to mid to late pregnancy may be due to changes in immune function over the course of pregnancy. These findings provide a basis for immune activation as a mechanism for previously observed associations between air pollution exposure during pregnancy and reduced birthweight, fetal growth restriction, and pregnancy complications.
ABSTRACT
PURPOSE: To investigate the use of the Lucy ® Stereotactic Phantom (Standard Imaging, Inc.) for Gamma Knife Perfexion radiosurgery quality assurance of the imaging, treatment planning, and dose delivery processes. End-to-end testing of the Perfexion and Gamma Plan version 10.1 has not been previously examined in literature. METHODS: The phantom was imaged using both the CT and T1- and T2-weighted MR sequences used for treatment planning. For imaging, the isocentric volume insert and fiducial markers were positioned within the phantom. Scans were transferred to the Gamma Plan treatment planning system and were evaluated for geometric and fusion accuracy. A plan was created to deliver 12Gy to the 50% isodose line to the 5.25cm3 volume. During dose delivery, Gafchromic EBT2 film was positioned in the film insert to replicate the position of the target volume. Dose results were analyzed using RIT software (Radiologic Imaging Technology, Inc.). RESULTS: Image fusion integrity was inspected by overlaying the MR and CT markers (5 fiducial markers spaced 5mm apart) and visually examining the resulting volume insert overlap between the three scans. Geometric accuracy was evaluated by contouring three volumes using Gamma Plan contouring tools. Agreement within 1.1%, 6.7% and 12.2% of the actual volumes was seen with the T1-weighted, T2-weighted, and CT images, respectively. The volume-based acquisition and 1mm slice thickness of the T1-weighted sequence resulted in the most accurate measurement. Geometric measurements along two dimensions showed acceptable accuracy for all imaging modalities within 1.6%. Dosimetry results agreed well with the planned dose. The EBT2 film was calibrated for absolute dose measurements using a dose calibration curve for 0.1-30 Gy and the calibration curve was verified to have <3% error above 1Gy. CONCLUSIONS: The Lucy phantom allows for comprehensive quality assurance testing of the Gamma Knife Perfexion radiosurgery process.
ABSTRACT
PURPOSE: To describe a TBI technique designed within the limits of a small-room geometry and its clinical implementation. METHODS: Following construction of the universal treatment devices, including the double-wedge, beam spoiler table, and patient support table, commissioning consists of measurements to determine the output, tissue-phantom ratio, effective source distance, and off-axis factor. Dose is calculated by applying these factors per patient-specific measurements to arbitrary point in the patient. Typically, ten calculation points are located at mid-separation along the mid-sagittal plane from the head to the ankles. When areas of unacceptably high dose are calculated, custom compensators are constructed from 5-mm sheets of PMMA and placed over the patient on top of the beam spoiler table. The typical dose homogeneity of the planning calculations is within 2% of the prescribed dose. RESULTS: To verify the accuracy of the technique, an anthropomorphic phantom was simulated and treated. In total, 128 thermoluminescent dosimeters (TLDs) were irradiated within the phantom. Concentrations of TLDs were located in the planes of selected calculation points, i.e. the head, neck, sternum, lung, umbilicus, and pelvis. Results showed the average dose to these locations differed from the intended dose by -3.5%, 3.4%, 2.6%, 9.5%, 2.8%, and 0.5%, respectively. Due to its heterogeneous material, a higher discrepancy in the lung dose was anticipated. To demonstrate the dosimetric size of the radiation field, ionization chamber measurements were taken on one lateral side of the treatment area at a constant depth of 5 cm. A few measurements on the contralateral side were within 1 %, verifying the field's lateral symmetry. The approximate treatment area for the current technique is approximately 180×50 cm. CONCLUSIONS: We have demonstrated a small-room technique capable of meeting the dosimetric goal of TBI. To improve the dosimetric characteristics, new universal treatment devices are currently being designed and constructed.
