Hybrid Computational Pregnant Female Phantom Construction for Radiation Dosimetry Applications

The number of patients undergoing diagnostic radiology and radiation therapy procedures has increased drastically owing to improvements in cancer diagnosis and treatment, and consequently, patient survival. However, the risk of secondary malignancies owing to radiation exposure remains a matter of concern. We previously published three hybrid computational fetal phantoms, which contained 27 fetal organs, as a starting point for developing the whole hybrid computational pregnant phantom set, which is the final objective of this study. An International Commission on Radiological Protection (ICRP) reference female voxel model was converted to a non-uniform rational B-spline (NURBS) surface model to construct a hybrid computational female phantom as a pregnant mother for each fetal model. Both fetal and maternal organs were matched with the ICRP- 89 reference data. To create a complete standard pregnant computational phantom set at 20, 30, and 35 weeks of pregnancy, the model mother's reproductive organs were removed, and fetal phantoms with appropriate placental and uterine models were added to the female pelvis using a 3D-modeling software. With the aid of radiological image sets that had originally been used to construct the fetal models, each fetal position and rotation inside the uterus were carefully adjusted to represent the real fetal locations inside the uterus. The major abdominal soft tissue organs below the diaphragm, namely the small intestine, large intestine, liver, gall bladder, stomach, pancreas, uterus, and urinary bladder, were removed from non-pregnant females. The resulting fetal phantom was positioned in the appropriate location, matching the original radiological image sets. An obstetrician-gynecologist reviewed the complete internal anatomy of all fetus phantoms and the pregnant women for accuracy, and suggested changes were implemented as needed. The remaining female anatomical tissues were reshaped and modified to accommodate the location of the fetus inside the uterus. This new series of hybrid computational pregnant phantom models provides realistic anatomical details that can be useful in evaluating fetal radiation doses in pregnant patients undergoing diagnostic imaging or radiotherapy procedures where realistic fetal computational human phantoms are required

Nanoparticle-mediated miR200-b delivery for the treatment of diabetic retinopathy

We recently reported that the Ins2Akita mouse is a good model for late-onset diabetic retinopathy. Here, we investigated the effect of miR200-b, a potential anti-angiogenic factor, on VEGF receptor 2 (VEGFR-2) expression and to determine the underlying angiogenic response in mouse endothelial cells, and in retinas from aged Ins2Akita mice. MiR200-b and its native flanking sequences were amplified and cloned into a pCAG-eGFP vector directed by the ubiquitous CAG promoter (namely pCAG-miR200-b-IRES-eGFP). The plasmid was compacted by CK30PEG10K into DNA nanoparticles (NPs) for in vivo delivery. Murine endothelial cell line, SVEC4-10, was first transfected with the plasmid. The mRNA levels of VEGF and VEGFR-2 were quantified by qRT-PCR and showed significant reduction in message expression compared with lipofectamine-transfected cells. Transfection of miR200-b suppressed the migration of SVEC4-10 cells. There was a significant inverse correlation between the level of expression of miR200-b and VEGFR-2. Intravitreal injection of miR200-b DNA NPs significantly reduced protein levels of VEGFR-2 as revealed by western blot and markedly suppressed angiogenesis as evaluated by fundus imaging in aged Ins2Akita mice even after 3 months of post-injection. These findings suggest that NP-mediated miR200-b delivery has negatively regulated VEGFR-2 expression in vivo

Construction of realistic hybrid computational fetal phantoms from radiological images in three gestational ages for radiation dosimetry applications

Radiation exposure and associated radiation risks are major concerns for fetal development for pregnant patients who undergo radiation therapy or diagnostic imaging procedures. In order to accurately estimate the radiation dose to the fetus and assess the uncertainty of fetal position and rotation, three hybrid computational fetus phantoms were constructed using magnetic resonance imaging (MRI) for each fetus model as a starting point to construct a complete anatomically accurate fetus, gravid uterus, and placenta. A total of 27 fetal organs were outlined from radiological images via the Velocity Treatment Planning System. The DICOM-Structure set was imported to Rhinoceros software for further reconstruction of 3D fetus phantom model sets. All fetal organ masses were compared with ICRP-89 reference data. Our fetal model series corresponds to 20, 31, and 35 weeks of pregnancy, thus covering the second and third trimester. Fetal positions and locations were carefully adapted to represent the real fetus locations inside the uterus for each trimester of pregnancy. The new series of hybrid computational fetus models together with pregnant female models can be used in evaluating fetal radiation doses in diagnostic imaging and radiotherapy procedures

FETUS PHANTOM CONSTRUCTIONS FOR OVERWEIGHT AND OBESE PREGNANT FEMALES FOR RADIOLOGICAL APPLICATIONS

Radiation exposure and associated radiation risks are major concerns for fetal development for pregnant patients in general, and in particular for overweight and obese pregnant patients who undergo diagnostic imaging or radiation therapy procedures. This dissertation describes a detailed research project related to the construction of hybrid computational phantoms, including the fetus and the pregnant female with the focus on overweight and obese patients, which can be used in radiological applications. In detail, a series of three hybrid computational fetus phantoms corresponding to a fetal age of 20, 31, and 35 weeks of pregnancy were constructed using highquality magnetic resonance imaging (MRI) sets obtained for three different patients. A total of 29 fetal organs were outlined from radiological images via the Velocity Treatment Planning System (TPS) and were imported to the three-dimensional (3D) modeling software package Rhinoceros for further reconstruction. The hybrid computational female phantom was constructed from the adult ICRP reference model which was converted from voxels into a non-uniform rational basis spline (NURBS) or mesh surface based phantom. A total of 35 different female organs and tissues were identified. All fetal and female organ masses were individually matched with the ICRP 89 Publication reference values. The hybrid computational pregnant female phantom series was constructed by individually adding the hybrid fetus model series to the hybrid female phantom. Fetal positions and locations were carefully adapted from MRI data and verified by a clinical specialist. Ultrasound data has also been used to determine the fetus body masses. Overweight and obese pregnant phantom models were derived from the developed standard hybrid computational pregnant series by adding different amounts of fat under the skin, except in the eye regions. They were carefully modeled using NURBS and/or polygon mesh geometry and include specified amounts of adipose tissue below the skin. The NURBS and mesh-based pregnant phantoms were then voxelized using the Binvox software and checked for consistency using the Viewvox and ImageJ software packages. This resulted in a set of pregnant female phantoms with body mass indexes ranging from 22.58 kg/m2 (normal body weight) to 34.24 kg/m2 (morbidly obese). This set of new phantoms can be used in the future to study the optimization of image quality and radiation dose for patients of different weight classifications. The ultimate goal is to create a library of all the data derived from these phantoms into a comprehensive dosimetry database defined in the Virtual Dose software. The new series of hybrid computational fetus models provide realistic anatomical details that can be useful in evaluating fetal radiation doses in pregnant patients undergoing diagnostic imaging or radiotherapy where realistic fetal computational human phantoms are required

FETUS PHANTOM CONSTRUCTIONS FOR OVERWEIGHT AND OBESE PREGNANT FEMALES FOR RADIOLOGICAL APPLICATIONS

Radiation exposure and associated radiation risks are major concerns for fetal development for pregnant patients in general , and in particular for overweight and obese pregnant patients who undergo diagnostic imaging or radiation therapy procedures. This dissertation describes a detailed research project related to the construction of hybrid computational phantoms , including the fetus and the pregnant female with the focus on overweight and obese patients , which can be used in radiological applications. In detail , a series of three hybrid computational fetus phantoms corresponding to a fetal age of 20 , 31 , and 35 weeks of pregnancy were constructed using highquality magnetic resonance imaging (MRI) sets obtained for three different patients. A total of 29 fetal organs were outlined from radiological images via the Velocity Treatment Planning System (TPS) and were imported to the three-dimensional (3D) modeling software package Rhinoceros for further reconstruction. The hybrid computational female phantom was constructed from the adult ICRP reference model which was converted from voxels into a non-uniform rational basis spline (NURBS) or mesh surface based phantom. A total of 35 different female organs and tissues were identified. All fetal and female organ masses were individually matched with the ICRP 89 Publication reference values. The hybrid computational pregnant female phantom series was constructed by individually adding the hybrid fetus model series to the hybrid female phantom. Fetal positions and locations were carefully adapted from MRI data and verified by a clinical specialist. Ultrasound data has also been used to determine the fetus body masses. Overweight and obese pregnant phantom models were derived from the developed standard hybrid computational pregnant series by adding different amounts of fat under the skin , except in the eye regions. They were carefully modeled using NURBS and/or polygon mesh geometry and include specified amounts of adipose tissue below the skin. The NURBS and mesh-based pregnant phantoms were then voxelized using the Binvox software and checked for consistency using the Viewvox and ImageJ software packages. This resulted in a set of pregnant female phantoms with body mass indexes ranging from 22.58 kg/m2 (normal body weight) to 34.24 kg/m2 (morbidly obese). This set of new phantoms can be used in the future to study the optimization of image quality and radiation dose for patients of different weight classifications. The ultimate goal is to create a library of all the data derived from these phantoms into a comprehensive dosimetry database defined in the Virtual Dose software. The new series of hybrid computational fetus models provide realistic anatomical details that can be useful in evaluating fetal radiation doses in pregnant patients undergoing diagnostic imaging or radiotherapy where realistic fetal computational human phantoms are required

Construction of realistic hybrid computational fetal phantoms from radiological images in three gestational ages for radiation dosimetry applications

Radiation exposure and associated radiation risks are major concerns for fetal development for pregnant patients who undergo radiation therapy or diagnostic imaging procedures. In order to accurately estimate the radiation dose to the fetus and assess the uncertainty of fetal position and rotation , three hybrid computational fetus phantoms were constructed using magnetic resonance imaging (MRI) for each fetus model as a starting point to construct a complete anatomically accurate fetus , gravid uterus , and placenta. A total of 27 fetal organs were outlined from radiological images via the Velocity Treatment Planning System. The DICOM-Structure set was imported to Rhinoceros software for further reconstruction of 3D fetus phantom model sets. All fetal organ masses were compared with ICRP-89 reference data. Our fetal model series corresponds to 20 , 31 , and 35 weeks of pregnancy , thus covering the second and third trimester. Fetal positions and locations were carefully adapted to represent the real fetus locations inside the uterus for each trimester of pregnancy. The new series of hybrid computational fetus models together with pregnant female models can be used in evaluating fetal radiation doses in diagnostic imaging and radiotherapy procedures.xt-

Construction of realistic hybrid computational fetal phantoms from radiological images in three gestational ages for radiation dosimetry applications

Radiation exposure and associated radiation risks are major concerns for fetal development forpregnant patients who undergo radiation therapy or diagnostic imaging procedures. In order toaccurately estimate the radiation dose to the fetus and assess the uncertainty of fetal position androtation, three hybrid computational fetus phantoms were constructed using magnetic resonanceimaging (MRI) for each fetus model as a starting point to construct a complete anatomically accuratefetus, gravid uterus, and placenta. A total of 27 fetal organs were outlined from radiological imagesvia the Velocity Treatment Planning System. The DICOM-Structure set was imported to Rhinocerossoftware for further reconstruction of 3D fetus phantom model sets. All fetal organ masses werecompared with ICRP-89 reference data. Our fetal model series corresponds to 20, 31, and 35 weeks ofpregnancy, thus covering the second and third trimester. Fetal positions and locations were carefullyadapted to represent the real fetus locations inside the uterus for each trimester of pregnancy. Thenew series of hybrid computational fetus models together with pregnant female models can be usedin evaluating fetal radiation doses in diagnostic imaging and radiotherapy procedures

Comparative analysis of DNA nanoparticles and AAVs for ocular gene delivery.

Gene therapy is a critical tool for the treatment of monogenic retinal diseases. However, the limited vector capacity of the current benchmark delivery strategy, adeno-associated virus (AAV), makes development of larger capacity alternatives, such as compacted DNA nanoparticles (NPs), critical. Here we conduct a side-by-side comparison of self-complementary AAV and CK30PEG NPs using matched ITR plasmids. We report that although AAVs are more efficient per vector genome (vg) than NPs, NPs can drive gene expression on a comparable scale and longevity to AAV. We show that subretinally injected NPs do not leave the eye while some of the AAV-injected animals exhibited vector DNA and GFP expression in the visual pathways of the brain from PI-60 onward. As a result, these NPs have the potential to become a successful alternative for ocular gene therapy, especially for the multitude of genes too large for AAV vectors