scholarly journals 3173 A Mouse Model to Study Image-Guided, Radiation-Induced Cardiac Injury and Potential Clinically Targetable Biologic Mediators

2019 ◽  
Vol 3 (s1) ◽  
pp. 101-101
Author(s):  
Alexandra Dreyfuss ◽  
Ioannis Verginadis ◽  
Khayrullo Shoniyozov ◽  
Paco Bravo ◽  
Steven Feigenberg ◽  
...  
Keyword(s):  
Mouse Model ◽  
Fdg Pet ◽  
Biochemical Markers ◽  
Cardiac Injury ◽  
Histopathological Analysis ◽  
Mouse Heart ◽  
Cardiac Damage ◽  
Image Guided ◽  
Radiation Induced

OBJECTIVES/SPECIFIC AIMS: The overall objective of this study is to develop a novel, clinically-relevant, image-guided mouse model for radiation-induced cardiotoxicity, which can be used to gain insight into clinically-targetable, pathophysiologic mechanisms of cardiac injury in thoracic radiotherapy patients. METHODS/STUDY POPULATION: Photon or sham radiation will be administered at differential doses to a defined portion of the heart and/or lungs of C57BL/6 female mice using micro-CT visualization of the heart with Xstrahl’s MuriSlice Software applied to the Small Animal Radiation Research Platform (SARRP). Cardiac and lung segments from a subset of mice will be harvested at specific time points for confirmation of radiation targeting, local apoptosis assessment, and evaluation of fibrosis and vascular tissue morphology. Quantitative echocardiography, myocardial 18F-fluorodeoxyglucose positron emission tomography computed tomography (18F-FDG PET/CT), and myocardial perfusion imaging (MPI) with Technicium-99 (Tc-99) sestamibi will be implemented to identify sensitive imaging measures of cardiac injury and asses myocardial mechanics, inflammation, and perfusion deficits, respectively. Concurrently, a multiparametric analysis will be conducted to identify novel, circulating biomarkers of cardiotoxicity. RESULTS/ANTICIPATED RESULTS: We hypothesize that a clinically-relevant mouse model can be generated by the in situ, focal irradiation of a portion of heart and/or lung tissue segments, and can be used to elucidate molecular mechanisms of radiation-induced cardiac damage. We anticipate time-dependent and dose-dependent, focal histopathologic changes in the mouse heart, with cardiac fibrosis development, vascular damage, and cellular apoptosis in irradiated mice. Additionally, we anticipate that our mouse model of focal heart irradiation will reveal radiologic and biochemical changes that can be used to characterize and predict radiation-induced cardiac injury. Specifically, we expect our quantitative echocardiography, FDG-PET, and MPI parameters to identify and characterize cardiac damage that topographically matches histopathological analysis, and expect levels of select biochemical markers to differentially vary with time. DISCUSSION/SIGNIFICANCE OF IMPACT: Our mouse model of radiation-induced cardiotoxicity has the potential to shift current preclinical research paradigms to more closely mimic the radiation plans most commonly administered in clinical practice. The primary technologic innovation to be developed here is the use of the SARRP to deliver image-guided, in situ, focal radiation to a defined portion of the mouse heart. From a conceptual perspective, we propose a novel approach for phenotyping radiation-induced cardiac damage in patients undergoing chest radiation therapy, integrating sensitive radiomic and biochemical markers into a predictive model of cardiotoxicity.

scholarly journals A Novel Mouse Model to Study Image-Guided, Radiation-Induced Intestinal Injury and Preclinical Screening of Radioprotectors

2016 ◽  
Vol 77 (4) ◽  
pp. 908-917 ◽  
Author(s):  
Ioannis I. Verginadis ◽  
Rahul Kanade ◽  
Brett Bell ◽  
Sravya Koduri ◽  
Edgar Ben-Josef ◽  
...  
Keyword(s):  
Mouse Model ◽  
Intestinal Injury ◽  
Image Guided ◽  
Radiation Induced ◽  
Preclinical Screening

scholarly journals Parvovirus Infection Is Associated With Myocarditis and Myocardial Fibrosis in Young Dogs

2017 ◽  
Vol 54 (6) ◽  
pp. 964-971 ◽  
Author(s):  
Jordan Ford ◽  
Laura McEndaffer ◽  
Randall Renshaw ◽  
Alex Molesan ◽  
Kathleen Kelly
Keyword(s):  
In Situ Hybridization ◽  
Myocardial Fibrosis ◽  
Messenger Rna ◽  
Cardiac Injury ◽  
Myocardial Necrosis ◽  
Myocardial Damage ◽  
Conventional Polymerase Chain Reaction ◽  
Cardiac Damage ◽  
Myocardial Lesions

Perinatal parvoviral infection causes necrotizing myocarditis in puppies, which results in acute high mortality or progressive cardiac injury. While widespread vaccination has dramatically curtailed the epidemic of canine parvoviral myocarditis, we hypothesized that canine parvovirus 2 (CPV-2) myocardial infection is an underrecognized cause of myocarditis, cardiac damage, and/or repair by fibrosis in young dogs. In this retrospective study, DNA was extracted from formalin-fixed, paraffin-embedded tissues from 40 cases and 41 control dogs under 2 years of age from 2007 to 2015. Cases had a diagnosis of myocardial necrosis, inflammation, or fibrosis, while age-matched controls lacked myocardial lesions. Conventional polymerase chain reaction (PCR) and sequencing targeting the VP1 to VP2 region detected CPV-2 in 12 of 40 cases (30%; 95% confidence interval [CI], 18%–45%) and 2 of 41 controls (5%; 95% CI, 0.1%–16%). Detection of CPV-2 DNA in the myocardium was significantly associated with myocardial lesions ( P = .003). Reverse transcription quantitative PCR amplifying VP2 identified viral messenger RNA in 12 of 12 PCR-positive cases and 2 of 2 controls. PCR results were confirmed by in situ hybridization, which identified parvoviral DNA in cardiomyocytes and occasionally macrophages of juvenile and young adult dogs (median age 61 days). Myocardial CPV-2 was identified in juveniles with minimal myocarditis and CPV-2 enteritis, which may indicate a longer window of cardiac susceptibility to myocarditis than previously reported. CPV-2 was also detected in dogs with severe myocardial fibrosis with in situ hybridization signal localized to cardiomyocytes, suggesting prior myocardial damage by CPV-2. Despite the frequency of vaccination, these findings suggest that CPV-2 remains an important cause of myocardial damage in dogs.

The Fine Structure of Irradiated Mouse Heart

1976 ◽  
Vol 34 ◽  
pp. 184-185
Author(s):  
Vivian V. Yang ◽  
S. Phyllis Stearner
Keyword(s):  
Microscopic Level ◽  
Ultrastructural Changes ◽  
Mouse Heart ◽  
Blood Vessel Wall ◽  
Histopathological Changes ◽  
Light Microscopic Level ◽  
Γ Rays ◽  
Fission Neutrons ◽  
Total Body

The heart is generally considered a radioresistant organ, and has received relatively little study after total-body irradiation with doses below the acutely lethal range. Some late damage in the irradiated heart has been described at the light microscopic level. However, since the dimensions of many important structures of the blood vessel wall are submicroscopic, investigators have turned to the electron microscope for adequate visualization of histopathological changes. Our studies are designed to evaluate ultrastructural changes in the mouse heart, particularly in the capillaries and muscle fibers, for 18 months after total-body exposure, and to compare the effects of 240 rad fission neutrons and 788 rad 60Co γ-rays.Three animals from each irradiated group and three control mice were sacrificed by ether inhalation at 4 days, and at 1, 3, 6, 12, and 18 months after irradiation. The thorax was opened and the heart was fixed briefly in situwith Karnofsky's fixative.

In situ TEM studies of irradiation effects for materials improvement

1991 ◽  
Vol 49 ◽  
pp. 452-453
Author(s):  
Charles W. Allen
Keyword(s):  
Nuclear Reactor ◽  
Austenitic Stainless Steels ◽  
High Energy ◽  
Point Of View ◽  
In Situ Tem ◽  
Irradiation Effects ◽  
Tem Analysis ◽  
Radiation Induced ◽  
Analytical Tools

Irradiation effects studies employing TEMs as analytical tools have been conducted for almost as many years as materials people have done TEM, motivated largely by materials needs for nuclear reactor development. Such studies have focussed on the behavior both of nuclear fuels and of materials for other reactor components which are subjected to radiation-induced degradation. Especially in the 1950s and 60s, post-irradiation TEM analysis may have been coupled to in situ (in reactor or in pile) experiments (e.g., irradiation-induced creep experiments of austenitic stainless steels). Although necessary from a technological point of view, such experiments are difficult to instrument (measure strain dynamically, e.g.) and control (temperature, e.g.) and require months or even years to perform in a nuclear reactor or in a spallation neutron source. Consequently, methods were sought for simulation of neutroninduced radiation damage of materials, the simulations employing other forms of radiation; in the case of metals and alloys, high energy electrons and high energy ions.

scholarly journals Radiation-induced lung fibrosis in a tumor-bearing mouse model is associated with enhanced Type-2 immunity

2015 ◽  
Vol 57 (2) ◽  
pp. 133-141 ◽  
Author(s):  
Jing Chen ◽  
Yacheng Wang ◽  
Zijie Mei ◽  
Shimin Zhang ◽  
Jie Yang ◽  
...  
Keyword(s):  
Mouse Model ◽  
Lung Fibrosis ◽  
Tumor Bearing Mouse ◽  
Tumor Bearing ◽  
Type 2 Immunity ◽  
Radiation Induced

scholarly journals Recurrent Chordoma Resection in the Advanced Multimodality Image Guided Operating Suite: 2-Dimensional Operative Video

2021 ◽  
Vol 20 (5) ◽  
pp. E344-E345
Author(s):  
Walid Ibn Essayed ◽  
Kaith K Almefty ◽  
Ossama Al-Mefty
Keyword(s):  
Skull Base ◽  
Surgical Resection ◽  
Petrous Apex ◽  
Tumor Control ◽  
Image Guided ◽  
Endoscopy Ultrasound ◽  
Radiation Induced ◽  
Multimodality Image ◽  
The Right ◽  
Operating Suite

Abstract Recurrent skull base chordomas are challenging lesions. They already had maximum radiation, and in the absence of any effective medical treatment, surgical resection is the only treatment.1,2 Surgery on recurrent previously radiated chordomas, however, carries much higher risk and the likelihood of subtotal resection. Maximizing tumor resection allows longer tumor control.3-5 The Advanced Multimodality Image Guided Operating Suite developed at the Brigham and Women's Hospital, Harvard Medical School, with the support of the National Institutes of Health, provides an optimal environment to manage these tumors. It offers the capability to obtain and integrate multiple modalities during surgery, including magnetic resonance imaging (MRI), positron emission tomography-computed tomography (PET-CT), endoscopy, ultrasound, fluoroscopy, and the ability to perform emergent endovascular procedures.5-7 The patient is a 39-yr-old male, presenting after 19 yr follow-up of a surgical resection and proton beam treatment for a skull base chordoma. He developed progressive ophthalmoplegia due to recurrence of his chordoma at the right petrous apex and cavernous sinus. Preoperative angiography demonstrated narrowing of the petrous segment of the right carotid artery suspect of radiation-induced angiopathy. The presence of radiation-induced angiopathy increases the risk of intraoperative carotid rupture, and the availability of endovascular intervention in the operative suite added favorable preparedness to deal with such complications if they happen. Given the clinical and radiological progression, surgical intervention was carried out through the prior zygomatic approach with the goal of performing maximum resection.8 The patient had an uneventful postoperative course and remained stable until he had a second recurrence 4 yr later. The patient consented to the procedure.

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