Intrinsic Susceptibility MRI Identifies Tumors with ALKF1174L Mutation in Genetically-Engineered Murine Models of High-Risk Neuroblastoma
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{"title"=>"Intrinsic susceptibility MRI identifies tumors with ALKF1174L mutation in genetically-engineered murine models of high-risk neuroblastoma", "type"=>"journal", "authors"=>[{"first_name"=>"Yann", "last_name"=>"Jamin", "scopus_author_id"=>"26655735100"}, {"first_name"=>"Laura", "last_name"=>"Glass", "scopus_author_id"=>"56149895500"}, {"first_name"=>"Albert", "last_name"=>"Hallsworth", "scopus_author_id"=>"34968088500"}, {"first_name"=>"Rani", "last_name"=>"George", "scopus_author_id"=>"8873898700"}, {"first_name"=>"Dow Mu", "last_name"=>"Koh", "scopus_author_id"=>"7103039100"}, {"first_name"=>"Andrew D.J.", "last_name"=>"Pearson", "scopus_author_id"=>"7401994312"}, {"first_name"=>"Louis", "last_name"=>"Chesler", "scopus_author_id"=>"6603378797"}, {"first_name"=>"Simon P.", "last_name"=>"Robinson", "scopus_author_id"=>"7402674201"}], "year"=>2014, "source"=>"PLoS ONE", "identifiers"=>{"sgr"=>"84899813436", "pmid"=>"24667968", "pui"=>"373020609", "issn"=>"19326203", "scopus"=>"2-s2.0-84899813436", "doi"=>"10.1371/journal.pone.0092886"}, "id"=>"ef5946c0-c250-3fce-8f22-3ae5f1fcf8f3", "abstract"=>"The early identification of children presenting ALK(F1174L)-mutated neuroblastoma, which are associated with resistance to the promising ALK inhibitor crizotinib and a marked poorer prognosis, has become a clinical priority. In comparing the radiology of the novel Th-ALK(F1174L)/Th-MYCN and the well-established Th-MYCN genetically-engineered murine models of neuroblastoma using MRI, we have identified a marked ALK(F1174L)-driven vascular phenotype. We demonstrate that quantitation of the transverse relaxation rate R2* (s(-1)) using intrinsic susceptibility-MRI under baseline conditions and during hyperoxia, can robustly discriminate this differential vascular phenotype, and identify MYCN-driven tumors harboring the ALK(F1174L) mutation with high specificity and selectivity. Intrinsic susceptibility-MRI could thus potentially provide a non-invasive and clinically-exploitable method to help identifying children with MYCN-driven neuroblastoma harboring the ALK(F1174L) mutation at the time of diagnosis.", "link"=>"http://www.mendeley.com/research/intrinsic-susceptibility-mri-identifies-tumors-alkf1174l-mutation-geneticallyengineered-murine-model", "reader_count"=>10, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Student > Doctoral Student"=>1, "Researcher"=>2, "Student > Ph. D. Student"=>1, "Student > Postgraduate"=>2, "Student > Master"=>2, "Lecturer"=>1}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Student > Doctoral Student"=>1, "Researcher"=>2, "Student > Ph. D. Student"=>1, "Student > Postgraduate"=>2, "Student > Master"=>2, "Lecturer"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>2, "Nursing and Health Professions"=>1, "Medicine and Dentistry"=>1, "Agricultural and Biological Sciences"=>4, "Pharmacology, Toxicology and Pharmaceutical Science"=>1, "Psychology"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>1}, "Psychology"=>{"Psychology"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>4}, "Nursing and Health Professions"=>{"Nursing and Health Professions"=>1}, "Unspecified"=>{"Unspecified"=>2}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>1}}, "group_count"=>1}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/1435088"], "description"=>"<p><b>A</b>) Anatomical transverse T<sub>2</sub>*-weighted MR images acquired at TE = 6.8 and 15.6 ms from representative Th-<i>ALK<sup>F1174L</sup></i>/Th-<i>MYCN</i> and Th-<i>MYCN</i> mice with abdominal neuroblastoma during initial air breathing, and at TE = 15.6 ms after 5 minutes of continuous inhalation of 100% oxygen. <b>B</b>) Corresponding parametric tumor transverse relaxation rate R<sub>2</sub>* maps calculated during initial air breathing and after 3 minutes of continuous inhalation of 100% oxygen. <b>C</b>) Resulting parametric tumor ΔR<sub>2</sub>*<sub>oxygen-air</sub> (R<sub>2</sub>*<sub>oxygen</sub>−R<sub>2</sub>*<sub>air</sub>) maps. <b>D</b>) Tumor R<sub>2</sub>* during initial air breathing, <b>E</b>) tumor R<sub>2</sub>* after 5 minutes of breathing 100% oxygen, and <b>F</b>) tumor ΔR<sub>2</sub>*<sub>oxygen-air</sub> (R<sub>2</sub>*<sub>oxygen</sub>−R<sub>2</sub>*<sub>air</sub>) were determined from Th-<i>ALK<sup>F1174L</sup></i>/Th-<i>MYCN</i> and Th-<i>MYCN</i> mice with abdominal neuroblastoma. Individual data points represent the mean of the median values determined from all three imaging slices for each animal, as well as the mean ±1 s.e.m, p, Student's 2-tailed unpaired t-test with a 5% level of significance.</p>", "links"=>[], "tags"=>["agriculture", "Agricultural biotechnology", "Genetically modified organisms", "biotechnology", "Genetic engineering", "genetics", "mutation", "Diagnostic medicine", "Diagnostic radiology", "Magnetic resonance imaging", "oncology", "Cancer detection and diagnosis", "Pediatric oncology", "pediatrics", "Child health", "Public and occupational health", "Radiology and imaging", "Model organisms", "Animal models", "Mouse models", "tumors", "harboring", "transgenic", "mice", "intrinsic", "susceptibility"], "article_id"=>974197, "categories"=>["Biological Sciences"], "users"=>["Yann Jamin", "Laura Glass", "Albert Hallsworth", "Rani George", "Dow-Mu Koh", "Andrew D. J. Pearson", "Louis Chesler", "Simon P. Robinson"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0092886.g002", "stats"=>{"downloads"=>2, "page_views"=>14, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Identification_of_tumors_harboring_the_ALK_F1174L_mutation_in_MYCN_driven_transgenic_mice_with_intrinsic_susceptibility_MRI_/974197", "title"=>"Identification of tumors harboring the <i>ALK<sup>F1174L</sup></i> mutation in <i>MYCN</i>-driven transgenic mice with intrinsic susceptibility MRI.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-03-25 04:10:53"}
  • {"files"=>["https://ndownloader.figshare.com/files/1435086"], "description"=>"<p><b>A</b>) Anatomical transverse T<sub>2</sub>-weighted MR images acquired with a rapid acquisition with refocused echoes (RARE) sequence and <b>B</b>) anatomical transverse T<sub>2</sub>*-weighted MR images acquired at increasing gradient echo times as indicated, from representative presenting with abdominal neuroblastoma. <b>C</b>) Note the rapidly decaying tumor signal intensity in the Th-MYCN mouse, compared to the more sustained tumor signal observed in the Th-<i>ALK<sup>F1174L</sup></i>/Th-<i>MYCN</i> mouse.</p>", "links"=>[], "tags"=>["agriculture", "Agricultural biotechnology", "Genetically modified organisms", "biotechnology", "Genetic engineering", "genetics", "mutation", "Diagnostic medicine", "Diagnostic radiology", "Magnetic resonance imaging", "oncology", "Cancer detection and diagnosis", "Pediatric oncology", "pediatrics", "Child health", "Public and occupational health", "Radiology and imaging", "Model organisms", "Animal models", "Mouse models", "mice", "abdominal"], "article_id"=>974195, "categories"=>["Biological Sciences"], "users"=>["Yann Jamin", "Laura Glass", "Albert Hallsworth", "Rani George", "Dow-Mu Koh", "Andrew D. J. Pearson", "Louis Chesler", "Simon P. Robinson"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0092886.g001", "stats"=>{"downloads"=>4, "page_views"=>18, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Radiological_comparison_of_the_Th_ALK_F1174L_Th_MYCN_and_Th_MYCN_mice_with_abdominal_neuroblastoma_/974195", "title"=>"Radiological comparison of the Th-<i>ALK<sup>F1174L</sup></i>/Th-<i>MYCN</i> and Th-<i>MYCN</i> mice with abdominal neuroblastoma.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-03-25 04:10:53"}
  • {"files"=>["https://ndownloader.figshare.com/files/1435090"], "description"=>"<p><b>A</b>) Gross pathology, <b>B</b>) composite images, and <b>C</b>) high magnification (x200) images from hematoxylin and eosin stained sections. Note the presence of large hemorrhagic regions filled with aggregated erythrocytes (*, blood lakes) extravasated from blood vessels (arrowed) in the tumor from the Th-<i>MYCN</i> mouse. <b>D</b>) Composite fluorescence images of uptake of the perfusion marker Hoechst 33342 into tumors from Th-<i>ALK<sup>F1174L</sup></i>/Th-<i>MYCN</i> and Th-<i>MYCN</i> mice with abdominal neuroblastoma. <b>E</b>) Quantitation of Hoechst 33342 uptake revealed significantly lower functionally perfused vasculature in tumors of Th-<i>ALK<sup>F1174L</sup></i>/Th-<i>MYCN</i> mice (n = 5) compared with tumors in Th-<i>MYCN</i> mice (n = 5). Data are mean ±1 s.e.m, p, Student's 2-tailed unpaired t-test with a 5% level of significance.</p>", "links"=>[], "tags"=>["agriculture", "Agricultural biotechnology", "Genetically modified organisms", "biotechnology", "Genetic engineering", "genetics", "mutation", "Diagnostic medicine", "Diagnostic radiology", "Magnetic resonance imaging", "oncology", "Cancer detection and diagnosis", "Pediatric oncology", "pediatrics", "Child health", "Public and occupational health", "Radiology and imaging", "Model organisms", "Animal models", "Mouse models", "tumors", "mice", "abdominal"], "article_id"=>974199, "categories"=>["Biological Sciences"], "users"=>["Yann Jamin", "Laura Glass", "Albert Hallsworth", "Rani George", "Dow-Mu Koh", "Andrew D. J. Pearson", "Louis Chesler", "Simon P. Robinson"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0092886.g003", "stats"=>{"downloads"=>0, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Pathological_comparison_of_tumors_from_Th_ALK_F1174L_Th_MYCN_and_Th_MYCN_mice_with_abdominal_neuroblastoma_/974199", "title"=>"Pathological comparison of tumors from Th-<i>ALK<sup>F1174L</sup></i>/Th-<i>MYCN</i> and Th-<i>MYCN</i> mice with abdominal neuroblastoma.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-03-25 04:10:53"}

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