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  1. Article: Feasibility Study of Ferumoxtyol for Contrast-enhanced MRI of Retroplacental Clear Space Disruption in Placenta Accreta Spectrum (PAS).

    Badachhape, Andrew A / Burnett, Brian / Bhandari, Prajwal / Devkota, Laxman / Bhavane, Rohan / Ghaghada, Ketan B / Yallampalli, Chandrasekhar / Fox, Karin A / Annapragada, Ananth V

    medRxiv : the preprint server for health sciences

    2023  

    Abstract: Introduction: Placenta accreta spectrum (PAS) occurs when the placenta is pathologically adherent to the myometrium. An intact retroplacental clear space (RPCS) is a marker of normal placentation, but visualization with conventional imaging techniques ... ...

    Abstract Introduction: Placenta accreta spectrum (PAS) occurs when the placenta is pathologically adherent to the myometrium. An intact retroplacental clear space (RPCS) is a marker of normal placentation, but visualization with conventional imaging techniques is a challenge. In this study, we investigate use of an FDA-approved iron oxide nanoparticle, ferumoxytol, for contrast-enhanced magnetic resonance imaging of the RPCS in mouse models of normal pregnancy and PAS. We then demonstrate the translational potential of this technique in human patients presenting with severe PAS (FIGO Grade 3C), moderate PAS (FIGO Grade 1), and no PAS.
    Methods: A T1-weighted gradient recalled echo (GRE) sequence was used to determine the optimal dose of ferumoxytol in pregnant mice. Pregnant Gab3
    Results: Ferumoxytol administered at 5 mg/kg produced strong T1 shortening in blood and led to strong placental enhancement in Fe-MRI images. Gab3
    Discussion: Ferumoxytol, an FDA-approved iron oxide nanoparticle formulation, enabled visualization of abnormal vascularization and loss of uteroplacental interface in a murine model of PAS. The potential of this non-invasive visualization technique was then further demonstrated in human subjects. Diagnosis of placental invasion using Fe-MRI may provide a sensitive method for clinical detection of PAS.
    Language English
    Publishing date 2023-03-24
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.03.20.23287436
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Advanced photon counting CT imaging pipeline for cardiac phenotyping of apolipoprotein E mouse models.

    Allphin, Alex J / Mahzarnia, Ali / Clark, Darin P / Qi, Yi / Han, Zay Y / Bhandari, Prajwal / Ghaghada, Ketan B / Badea, Alexandra / Badea, Cristian T

    PloS one

    2023  Volume 18, Issue 10, Page(s) e0291733

    Abstract: Background: Cardiovascular disease (CVD) is associated with the apolipoprotein E (APOE) gene and lipid metabolism. This study aimed to develop an imaging-based pipeline to comprehensively assess cardiac structure and function in mouse models expressing ... ...

    Abstract Background: Cardiovascular disease (CVD) is associated with the apolipoprotein E (APOE) gene and lipid metabolism. This study aimed to develop an imaging-based pipeline to comprehensively assess cardiac structure and function in mouse models expressing different APOE genotypes using photon-counting computed tomography (PCCT).
    Methods: 123 mice grouped based on APOE genotype (APOE2, APOE3, APOE4, APOE knockout (KO)), gender, human NOS2 factor, and diet (control or high fat) were used in this study. The pipeline included PCCT imaging on a custom-built system with contrast-enhanced in vivo imaging and intrinsic cardiac gating, spectral and temporal iterative reconstruction, spectral decomposition, and deep learning cardiac segmentation. Statistical analysis evaluated genotype, diet, sex, and body weight effects on cardiac measurements.
    Results: Our results showed that PCCT offered high quality imaging with reduced noise. Material decomposition enabled separation of calcified plaques from iodine enhanced blood in APOE KO mice. Deep learning-based segmentation showed good performance with Dice scores of 0.91 for CT-based segmentation and 0.89 for iodine map-based segmentation. Genotype-specific differences were observed in left ventricular volumes, heart rate, stroke volume, ejection fraction, and cardiac index. Statistically significant differences were found between control and high fat diets for APOE2 and APOE4 genotypes in heart rate and stroke volume. Sex and weight were also significant predictors of cardiac measurements. The inclusion of the human NOS2 gene modulated these effects.
    Conclusions: This study demonstrates the potential of PCCT in assessing cardiac structure and function in mouse models of CVD which can help in understanding the interplay between genetic factors, diet, and cardiovascular health.
    MeSH term(s) Mice ; Humans ; Animals ; Apolipoprotein E2/genetics ; Apolipoprotein E4/genetics ; Apolipoproteins E/genetics ; Apolipoprotein E3/genetics ; Tomography, X-Ray Computed ; Mice, Knockout ; Cardiovascular Diseases/diagnostic imaging ; Cardiovascular Diseases/genetics ; Iodine
    Chemical Substances Apolipoprotein E2 ; Apolipoprotein E4 ; Apolipoproteins E ; Apolipoprotein E3 ; Iodine (9679TC07X4)
    Language English
    Publishing date 2023-10-05
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 2267670-3
    ISSN 1932-6203 ; 1932-6203
    ISSN (online) 1932-6203
    ISSN 1932-6203
    DOI 10.1371/journal.pone.0291733
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: A surrogate marker for very early-stage tau pathology is detectable by molecular magnetic resonance imaging.

    Parekh, Parag / Mu, Qingshan / Badachhape, Andrew / Bhavane, Rohan / Srivastava, Mayank / Devkota, Laxman / Sun, Xianwei / Bhandari, Prajwal / Eriksen, Jason L / Tanifum, Eric / Ghaghada, Ketan / Annapragada, Ananth

    Theranostics

    2022  Volume 12, Issue 12, Page(s) 5504–5521

    Abstract: The abnormal phosphorylation of tau is a necessary precursor to the formation of tau fibrils, a marker of Alzheimer's disease. We hypothesize that hyperphosphorylative conditions may result in unique cell surface markers. We identify and demonstrate the ... ...

    Abstract The abnormal phosphorylation of tau is a necessary precursor to the formation of tau fibrils, a marker of Alzheimer's disease. We hypothesize that hyperphosphorylative conditions may result in unique cell surface markers. We identify and demonstrate the utility of such surrogate markers to identify the hyperphosphorylative state.
    MeSH term(s) Alzheimer Disease/pathology ; Animals ; Biomarkers ; Disease Models, Animal ; Magnetic Resonance Imaging ; Mice ; Mice, Transgenic ; Vimentin ; tau Proteins/metabolism
    Chemical Substances Biomarkers ; Vimentin ; tau Proteins
    Language English
    Publishing date 2022-07-18
    Publishing country Australia
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2592097-2
    ISSN 1838-7640 ; 1838-7640
    ISSN (online) 1838-7640
    ISSN 1838-7640
    DOI 10.7150/thno.72258
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Nanoparticle Contrast-enhanced MRI for Visualization of Retroplacental Clear Space Disruption in a Mouse Model of Placental Accreta Spectrum (PAS).

    Badachhape, Andrew A / Bhandari, Prajwal / Devkota, Laxman / Srivastava, Mayank / Tanifum, Eric A / George, Verghese / Fox, Karin A / Yallampalli, Chandrasekhar / Annapragada, Ananth V / Ghaghada, Ketan B

    Academic radiology

    2022  Volume 30, Issue 7, Page(s) 1384–1391

    Abstract: Introduction: Prior preclinical studies established the utility of liposomal nanoparticle blood-pool contrast agents in visualizing the retroplacental clear space (RPCS), a marker of normal placentation, while sparing fetuses from exposure because the ... ...

    Abstract Introduction: Prior preclinical studies established the utility of liposomal nanoparticle blood-pool contrast agents in visualizing the retroplacental clear space (RPCS), a marker of normal placentation, while sparing fetuses from exposure because the agent does not cross the placental barrier. In this work, we characterized RPCS disruption in a mouse model of placenta accreta spectrum (PAS) using these agents.
    Materials and methods: Contrast-enhanced MRI (CE-MRI) and computed tomography (CE-CT) using liposomal nanoparticles bearing gadolinium (liposomal-Gd) and iodine were performed in pregnant Gab3
    Results: Pregnant Gab3
    Discussion: Imaging of the Gab3
    MeSH term(s) Female ; Pregnancy ; Animals ; Mice ; Placenta/diagnostic imaging ; Contrast Media ; Magnetic Resonance Imaging ; Disease Models, Animal ; Nanoparticles ; Retrospective Studies ; Adaptor Proteins, Signal Transducing
    Chemical Substances Contrast Media ; Gab3 protein, mouse ; Adaptor Proteins, Signal Transducing
    Language English
    Publishing date 2022-09-24
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1355509-1
    ISSN 1878-4046 ; 1076-6332
    ISSN (online) 1878-4046
    ISSN 1076-6332
    DOI 10.1016/j.acra.2022.08.025
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

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  5. Article ; Online: Pre-clinical dose-ranging efficacy, pharmacokinetics, tissue biodistribution, and toxicity of a targeted contrast agent for MRI of amyloid deposition in Alzheimer's disease.

    Badachhape, Andrew A / Working, Peter K / Srivastava, Mayank / Bhandari, Prajwal / Stupin, Igor V / Devkota, Laxman / Tanifum, Eric A / Annapragada, Ananth V / Ghaghada, Ketan B

    Scientific reports

    2020  Volume 10, Issue 1, Page(s) 16185

    Abstract: In these preclinical studies, we describe ADx-001, an Aβ-targeted liposomal macrocyclic gadolinium (Gd) imaging agent, for MRI of amyloid plaques. The targeting moiety is a novel lipid-PEG conjugated styryl-pyrimidine. An MRI-based contrast agent such as ...

    Abstract In these preclinical studies, we describe ADx-001, an Aβ-targeted liposomal macrocyclic gadolinium (Gd) imaging agent, for MRI of amyloid plaques. The targeting moiety is a novel lipid-PEG conjugated styryl-pyrimidine. An MRI-based contrast agent such as ADx-001 is attractive because of the lack of radioactivity, ease of distribution, long shelf life, and the prevalence of MRI scanners. Dose-ranging efficacy studies were performed on a 1 T MRI scanner using a transgenic APP/PSEN1 mouse model of Alzheimer's disease. ADx-001 was tested at 0.10, 0.15, and 0.20 mmol Gd/kg. Gold standard post-mortem amyloid immunostaining was used for the determination of sensitivity and specificity. ADx-001 toxicity was evaluated in rats and monkeys at doses up to 0.30 mmol Gd/kg. ADx-001 pharmacokinetics were determined in monkeys and its tissue distribution was evaluated in rats. ADx-001-enhanced MRI demonstrated significantly higher (p < 0.05) brain signal enhancement in transgenic mice relative to wild type mice at all dose levels. ADx-001 demonstrated high sensitivity at 0.20 and 0.15 mmol Gd/kg and excellent specificity at all dose levels for in vivo imaging of β amyloid plaques. ADx-001 was well tolerated in rats and monkeys and exhibited the slow clearance from circulation and tissue biodistribution typical of PEGylated nanoparticles.
    MeSH term(s) Alzheimer Disease/diagnostic imaging ; Alzheimer Disease/genetics ; Alzheimer Disease/metabolism ; Amyloid/metabolism ; Amyloid beta-Protein Precursor/genetics ; Animals ; Contrast Media/administration & dosage ; Contrast Media/pharmacokinetics ; Disease Models, Animal ; Dose-Response Relationship, Drug ; Humans ; Macaca fascicularis ; Magnetic Resonance Imaging/methods ; Male ; Mice ; Mice, Transgenic ; Peptide Fragments/metabolism ; Plaque, Amyloid/diagnostic imaging ; Plaque, Amyloid/genetics ; Plaque, Amyloid/metabolism ; Presenilin-1/genetics ; Rats ; Tissue Distribution
    Chemical Substances Amyloid ; Amyloid beta-Protein Precursor ; Contrast Media ; Peptide Fragments ; Presenilin-1
    Language English
    Publishing date 2020-09-30
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-020-73233-7
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