Skin dose in longitudinal and transverse linac-MRIs using Monte Carlo and realistic 3D MRI field models.

PURPOSE: The magnetic fields of linac-MR systems modify the path of contaminant electrons in photon beams, which alters patient skin dose. To accurately quantify the magnitude of changes in skin dose, the authors use Monte Carlo calculations that incorporate realistic 3D magnetic field models of longitudinal and transverse linac-MR systems. METHODS: Finite element method (FEM) is used to generate complete 3D magnetic field maps for 0.56 T longitudinal and transverse linac-MR magnet assemblies, as well as for representative 0.5 and 1.0 T Helmholtz MRI systems. EGSnrc simulations implementing these 3D magnetic fields are performed. The geometry for the BEAMnrc simulations incorporates the Varian 600C 6 MV linac, magnet poles, the yoke, and the magnetic shields of the linac-MRIs. Resulting phase-space files are used to calculate the central axis percent depth-doses in a water phantom and 2D skin dose distributions for 70 µm entrance and exit layers using DOSXYZnrc. For comparison, skin doses are also calculated in the absence of magnetic field, and using a 1D magnetic field with an unrealistically large fringe field. The effects of photon field size, air gap (longitudinal configuration), and angle of obliquity (transverse configuration) are also investigated. RESULTS: Realistic modeling of the 3D magnetic fields shows that fringe fields decay rapidly and have a very small magnitude at the linac head. As a result, longitudinal linac-MR systems mostly confine contaminant electrons that are generated in the air gap and have an insignificant effect on electrons produced further upstream. The increase in the skin dose for the longitudinal configuration compared to the zero B-field case varies from ∼1% to ∼14% for air gaps of 5-31 cm, respectively. (All dose changes are reported as a % of D(max).) The increase is also field-size dependent, ranging from ∼3% at 20 × 20 cm(2) to ∼11% at 5 × 5 cm(2). The small changes in skin dose are in contrast to significant increases that are calculated for the unrealistic 1D magnetic field. For the transverse configuration, the entrance skin dose is equal or smaller than that of the zero B-field case for perpendicular beams. For a 10 × 10 cm(2) oblique beam the transverse magnetic field decreases the entry skin dose for oblique angles less than ±20° and increases it by no more than 10% for larger angles up to ±45°. The exit skin dose is increased by 42% for a 10 × 10 cm(2) perpendicular beam, but appreciably drops and approaches the zero B-field case for large oblique angles of incidence. CONCLUSIONS: For longitudinal linac-MR systems only a small increase in the entrance skin dose is predicted, due to the rapid decay of the realistic magnetic fringe fields. For transverse linac-MR systems, changes to the entrance skin dose are small for most scenarios. For the same geometry, on the exit side a fairly large increase is observed for perpendicular beams, but significantly drops for large oblique angles of incidence. The observed effects on skin dose are not expected to limit the application of linac-MR systems in either the longitudinal or transverse configuration.

Geometric distortion and shimming considerations in a rotating MR-linac design due to the influence of low-level external magnetic fields.

PURPOSE: This work investigates with simulation the effect of external stray magnetic fields on a recently reported MRI-linac hybrid, which by design will rotate about the patient axis during therapy. During rotation, interactions with magnetic fields from the earth or nearby ferromagnetic structures may cause unacceptable field distortions in the imaging field of view. Optimal approaches for passive shimming implementation, the degree and significance of residual distortion, and an analysis of the active shimming requirements for further correction are examined. METHODS: Finite element simulations were implemented on two representative types of biplanar magnet designs. Each of these magnet designs, consisting of a 0.2 T four-post and a 0.5 T C-type unit, was simulated with and without an external field on the order of the earth's field (0.5 G) over a range of rotated positions. Through subtraction, the field distribution resulting from the external field alone could be determined. These measured distributions were decomposed into spherical harmonic components, which were then used to investigate the effect of their selective removal to simulate the effects of passive and active shimming. Residual fields after different levels of shim treatment were measured and assessed in terms of their imaging consequence. RESULTS: For both magnet types, the overall success of a passive shim implementation was highly dependent on the orientation for which it was based. If this orientation was chosen incorrectly, the passive shim would correct for the induced fields at that location, but the overall maximal distortion at other locations was exacerbated by up to a factor of two. The choice of passive shim orientation with the least negative consequence was found to be that where the magnet B(0) axis and transaxial component of the external field were aligned. Residual fields after passive shimming and frequency offset were found to be low in the simulated scenarios, contributing to <1 mm of distortion for most standard imaging sequences (based on a 0.5 G external field). However, extremely rapid single-shot sequences could be distorted by these residual fields to well over 5 mm. These residuals when analyzed were found to correspond primarily to second-order spherical harmonic terms. One term in particular was found to account for the vast majority of these residual fields, defined by the product of the two axes perpendicular to the axis of rotation. The implementation of this term would allow the resulting geometric distortion to fall to the order of 1 mm, even for single-shot sequences. CONCLUSIONS: After appropriate passive shimming, the imaging distortion due to an external field of 0.5 G was found to be important only in rapid single-shot sequences, which are especially susceptible to field inhomogeneity. Should it be desirable to use these sequences for real-time tracking, made conceivable due to the lower susceptibility concerns at low field, these residual fields should be addressed. The ability to use only one second-order term for this correction will reduce the cost impact of this decision.

Synchronous bilateral infiltrating syringomatous adenoma of the breast.

Infiltrating syringomatous breast adenoma is an uncommon mammary neoplasm composed of angulated glandular structures with a variable amount of epidermoid differentiation which proliferate in a background of dense collagenous stroma. The patient presented with bilateral hardness and oedema of the nipples. Ultrasound and mammography revealed microcalcifications in retromammilary regions of both nipples. Histological examination of the resected specimens showed angulated glands and solid cords, lined by an inner layer of epithelial cells and an outer layer of myoepithelial cells, immersed in desmoplastic stroma. Within the solid cords reminiscent of squamous cells, occasionally aggregated in keratinizing cysts were found. To the best of our knowledge this is the first described case of bilateral infiltrating syringomatous breast adenoma with synchronous presentation. Infiltrating syringomatous adenoma is a rare lesion. A finding of infiltrating syringomatous adenoma in one breast should prompt careful examination of the opposite breast with adequate follow-up.

WE-E-BRB-06: Monte Carlo Calculations of the Skin Dose for Longitudinal Linac-MR System Using Realistic Three-Dimensional Magnetic Field Modeling.

PURPOSE: This study quantifies the effects of the magnetic field of a longitudinal linac-MR system (B-field parallel to beam direction) on skin dose due to the confinement of contaminant electrons, using Monte Carlo calculations and realistic 3-D models of the magnetic field. METHODS: The complete realistic 3-D magnetic fields generated by the bi-planar Linac-MR magnet assembly are calculated with the finite element method using Opera- 3D. EGSnrc simulations are performed in the presence of ∼0.6T and IT MRI fields that have realistic rapid fall-off of the fringe field. The simulation geometry includes a Varian 600C 6MV linac, the yoke and magnetic shields of the MRIs, and features an isocentre distance of 126 cm. Phase spaces at the surface of a water phantom are scored using BEAMnrc; DOSXYZnrc is used to score the resulting CAX percent depth-doses in the phantom and the 2D skin dose distributions in the first 70 urn layer. For comparison, skin doses are also calculated in the absence of magnetic field and using a 1-D magnetic field with an unrealistic fringe field. The effects of field size and air gap (between phantom surface and magnet pole) are also examined. RESULTS: Analysis of the phase-space and dose distributions reveals that significant containment of electrons occurs primarily close to the uniform magnetic field region. The increase in skin dose due to the magnetic field depends on the air gap, varying from 1% to 13% for air gaps of 5 to 31 cm, respectively. The increase is also field-size dependent, varying from 3% at 20×20 cm2 to 11% at 5×5 cm2. CONCLUSIONS: Calculations based on various realistic MRI 3D magnetic-field maps that appropriately account for the rapid decay of the fringe field show that the increase in the patient skin dose of a longitudinal Linac-MR system is clinically insignificant.

Poster - Thurs Eve-08: Passive shimming optimization of a permanent magnet structure for a prototype coupled MRI-medical linear accelerator.

The ultimate goal of radiation therapy is to increase tumor control while reducing normal tissue complications. This is accomplished by conforming the radiation dose delivered to a patient to the tumor geometry, permitting the delivery of higher doses to the target volume while decreasing the dose in surrounding normal tissues. In order to best achieve this goal, our group is pursuing the design of a 0.2T biplanar magnetic resonance imager (MRI) coupled with a medical linear accelerator, which will be capable of performing real-time image guided radiotherapy. In a simplified design of the permanent magnet structure for this system, large paramagnetic plates which affect the characteristics of the magnetic field in the imaging volume are used to hold the magnetic material in place. Since the sole purpose of the MRI module of this unit is to provide geometrical information regarding the shape and position of the target volume during irradiation, obtaining distortion-free images is critical. In the present work, we seek a particular surface topology on the pole plates of the permanent magnet structure which minimizes the overall size of the pole plates while maximizing the homogeneity of the magnetic field in the imaging volume. A rose ring design is investigated with the aid of finite element analysis and the results indicate that a significant improvement in field uniformity is obtained as compared to the simplest design possible.

Perinatal outcome of pregnancies in women aged 40 and over.

Perinatal outcome of pregnancies at forty and over was analyzed starting from the diagnosis of pregnancy to seven days following delivery. Retrospectively, pre-gestational health and reproduction status were dealt with, as well as the course of pregnancy, deliveries, and newborn children (study group). The control group was composed of pregnant women aged 20 to 29, who were identical to study group in terms of parity. Statistical data processing was done by means of chi2-test, and contingency 2 x 2 tables. The difference was significant if p < 0.05. Out of 2,099 diagnosed wanted pregnancies at forty and over, 415 (19.8%) had a miscarriage, in 33 (1.6%) an artificial abortion was performed after determining the fetus karyotype and 1,651 (78.2%) of pregnant women delivered. In 66.2% of pregnancies the fetus karyotype was determined and in 33 (2.5%) fetuses chromosomal abnormalities were found Incidence of deliveries at 40 and over is 1.38%, which is a 35.6-percent increase in the last ten years. Nullipara and pluripara had an increase, and multipara had a decrease. Pre-gestational health and reproduction status in study group is lower than in control group. Complications during pregnancy: threatened abortion, EPH gestosis, placenta praevia, gestational diabetes, late fetal death are more frequent than in control group (p < 0.05). In intrapartal terms, more frequent were induction of delivery, meconium-stained amniotic fluid, fetal distress, operative vaginal deliveries, and Cesarean section (p < 0.05). In neonatal outcome there are more premature infant, there are more VLBW, LBW, SGA, newborn with low Apgar index values, and the total perinatal death is greater than in the control group (p < 0.05). In perinatal terms, (from the diagnosis to the seventh day following delivery) 1,617 children survived (77.0%), meaning that perinatal loss was 482 (23.0%). Authors conclude that pregnancy at 40 and over is a high-risk pregnancy. There is a high risk of pre-gestational and gestational complications, and perinatal loss is high. Therefore, those pregnancies are not desirable from the medical point of view.

Dlx5 induces expression of COL1A1 promoter contained in a retrovirus vector.

AIM: To determine whether retrovirally expressed Dlx5, a homeobox-containing transcription factor, can induce a 2.3 kb rat COL1A1 promoter-reporter construct, which is transduced into osteoblastic cells by the use of a retrovirus vector. METHODS: A self-inactivating retrovirus vector containing the rat COL1A1 driving green fluorescent protein (GFP) was transduced into chick calvarial periosteal cells. These cells were then infected with a replication-competent retroviral vector expressing Dlx5, or a control vector. The cells were cultured in the presence of ascorbic acid and beta-glycerol-phosphate, which promotes osteoblastic differentiation. Expression of the COL1A1 promoter was assessed by detecting GFP with fluorescence microscopy. RESULTS: GFP was detected only in cells infected with the Dlx5 expressing retrovirus. The GFP positive cells were observed in regions of the culture that had undergone osteoblastic differentiation, as detected by cell morphology and the presence of a mineralized matrix. CONCLUSION: The 2.3 kb rat COL1A1 promoter fragment contains elements responsive to Dlx5, and the self-inactivating retroviral vector allows these elements to be used appropriately.

Premature termination codon in the aggrecan gene of nanomelia and its influence on mRNA transport and stability.

AIM: To analyze the influence of the premature termination codon on mRNA transport and stability METHODS: Chondrocyte mRNA was isolated from homozygous and heterozygous nanomelic 17-days old embryos and examined by RT-PCR analysis. To analyze aggrecan mRNA stability, mRNA synthesis was inhibited with DRB [5,6 dichloro-1-(-D-ribofuranosyl benzimidazole)], a specific inhibitor of RNA polymerase II. Visualization of the aggrecan alleles was performed by in situ hybridization. RESULTS: The level of mutant aggrecan mRNA within the nucleus was equal to that of the control, but no mutant mRNA was observed in the cytoplasm. RT-PCR revealed that the mutant transcript was only detectable in the nucleus, compared with house-keeping glyceraldehyde-3-phosphate dehydrogenase (GAPDH) gene or collagen type II. A restriction site induced by premature termination codon TAA allowed the distinction of normal and mutant transcripts in chondrocytes derived from embryos heterozygous for the nanomelic mutation. After the treatment with DRB, identical decay rates were demonstrated for both transcripts within the heterozygous nucleus. In situ hybridization showed no abnormal mRNA accumulation. CONCLUSION: This is the first evidence suggesting that the transcript of the mRNA with the premature termination codon within an exon does exit the nucleus.

Ectopic Msx2 overexpression inhibits and Msx2 antisense stimulates calvarial osteoblast differentiation.

Msx2 is believed to play a role in regulating bone development, particularly in sutures of cranial bone. In this study we investigated the effects of retroviral-mediated overexpression of Msx2 mRNA, in both sense and antisense orientations, on primary cultured chick calvarial osteoblasts. Unregulated overexpression of sense mRNA produced high levels of Msx2 protein throughout the culture period, preventing the expected fall as the cells differentiate. The continued high expression of Msx2 prevented osteoblastic differentiation and mineralization of the extracellular matrix. In contrast, expression of antisense Msx2 RNA decreased proliferation and accelerated differentiation. In other studies, we showed that the Msx2 promoter was widely expressed during the proliferative phase of mouse calvarial osteoblast cultures but was preferentially downregulated in osteoblastic nodules. These results support a model in which Msx2 prevents differentiation and stimulates proliferation of cells at the extreme ends of the osteogenic fronts of the calvariae, facilitating expansion of the skull and closure of the suture.

BPC 157's effect on healing.

The 15 amino acid agent BPC 157, showing a wide range of organoprotective action in different experimental models, was used in our experiments in order to establish its influence on different elements connected with the healing process. Elements thought to be of greatest importance in the process of healing are formation of granulation tissue, angiogenesis and production of collagen. In our work we tested the influence of BPC 157 on: granulation tissue and collagen formation, on angiogenesis as well as on tensile strength development, using three experimental rat models: 1) skin incisional wounds; 2) colon-colon anastomoses; and 3) angiogenesis model with synthetic sponge implantation. The specimens were histologically assessed for collagen, reticulin and blood vessels using scoring and morphometry. In all experiments significant differences between BPC 157-treated animals and controls were found, showing a strong, promoting involvement of BPC in the healing process. It is worth noting that these effects were achieved by different routes of application, including intragastric and local, making BPC 157 a potentially useful therapeutic agent.

Analysis of metal diffusion from crown to the human teeth.

Proton induced X-ray emission spectroscopy (PIXE) has been used to determine the intensity of metals from crowns in human teeth. In order to measure elements distribution across the tooth section, proton beam (3 MeV) has been collimeted to provide a spatial resolution of 300 microns. The samples were selected according to the time of insertion of crowns and the kind of alloys they were made of. The results show the intensities of gold, zinc and copper in abutment teeth. It was not found any intensity of paladium and amount of silver was not significant.