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      Multiparametric Classification of Skin from Osteogenesis Imperfecta Patients and Controls by Quantitative Magnetic Resonance Microimaging

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          Abstract

          The purpose of this study is to evaluate the ability of quantitative magnetic resonance imaging (MRI) to discriminate between skin biopsies from individuals with osteogenesis imperfecta (OI) and skin biopsies from individuals without OI. Skin biopsies from nine controls (unaffected) and nine OI patients were imaged to generate maps of five separate MR parameters, T 1, T 2, k m, MTR and ADC. Parameter values were calculated over the dermal region and used for univariate and multiparametric classification analysis. A substantial degree of overlap of individual MR parameters was observed between control and OI groups, which limited the sensitivity and specificity of univariate classification. Classification accuracies ranging between 39% and 67% were found depending on the variable of investigation, with T 2 yielding the best accuracy of 67%. When several MR parameters were considered simultaneously in a multivariate analysis, the classification accuracies improved up to 89% for specific combinations, including the combination of T 2 and k m. These results indicate that multiparametric classification by quantitative MRI is able to detect differences between the skin of OI patients and of unaffected individuals, which motivates further study of quantitative MRI for the clinical diagnosis of OI.

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          Most cited references35

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          Genetic heterogeneity in osteogenesis imperfecta.

          An epidemiological and genetical study of osteogenesis imperfecta (OI) in Victoria, Australia confirmed that there are at least four distinct syndromes at present called OI. The largest group of patients showed autosomal dominant inheritance of osteoporosis leading to fractures and distinctly blue sclerae. A large proportion of adults had presenile deafness or a family history of presenile conductive hearing loss. A second group, who comprised the majority of newborns with neonatal fractures, all died before or soon after birth. These had characteristic broad, crumpled femora and beaded ribs in skeletal x-rays. Autosomal recessive inheritance was likely for some, if not all, of these cases. A third group, two thirds of whom had fractures at birth, showed severe progressive deformity of limbs and spine. The density of scleral blueness appeared less than that seen in the first group of patients and approximated that seen in normal children and adults. Moreover, the blueness appeared to decrease with age. All patients in this group were sporadic cases. The mode of inheritance was not resolved by the study, but it is likely that the group is heterogeneous with both dominant and recessive genotypes responsible for the syndrome. The fourth group of patients showed dominant inheritance of osteoporosis leading to fractures, with variable deformity of long bones, but normal sclerae.
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            The human type I collagen mutation database.

            Type I collagen is the most abundant and ubiquitously distributed of the collagen family of proteins. It is a heterotrimer comprising two alpha1(I) chains and one alpha2(I) chain which are encoded by the unlinked loci COL1A1 and COL1A2 respectively. Mutations at these loci result primarily in the connective tissue disorders osteogenesis imperfecta and Ehlers-Danlos syndrome types VIIA and VIIB. Two instances of osteoporosis and a single instance of Marfan syndrome are also the result of mutations at these loci. The mutation data are accessible on the world wide web at http://www.le.ac.uk/depts/ge/collagen/collagen.html
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              The Human Collagen Mutation Database 1998.

              The collagens are a large and diverse family of proteins which are found in the extracellular matrix. In common with one another, the 19 known collagen types have triple-helical domains of variable length but they differ with respect to their overall size and the nature and location of their globular domains. Collagen mutations lead to heritable defects of connective tissues and mutation data for collagen types I and III are presented here. The mutation data are accessible on the world wide web at http://www.le.ac.uk/genetics/collagen/
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                14 July 2016
                2016
                : 11
                : 7
                : e0157891
                Affiliations
                [1 ]Laboratory of Clinical Investigation, Magnetic Resonance Imaging and Spectroscopy Section, National Institute on Aging, National Institutes of Health, Baltimore, Maryland, United States of America
                [2 ]Kathryn O. and Alan C. Greenberg Center for Skeletal Dysplasias, Hospital for Special Surgery, New York, New York, United States of America
                [3 ]Core Imaging Facility for Small Animals, GRU Cancer Center, Augusta University Augusta, Georiga, United States of America
                [4 ]Department of Bioengineering, College of Engineering, Temple University, Philadelphia, United States of America
                [5 ]Department of Orthopaedics, Hospital for Special Surgery, New York, New York, United States of America
                Banner Alzheimer's Institute, UNITED STATES
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: CLR NP RGS KWF. Performed the experiments: KWF. Analyzed the data: BGA KFW PCL NP RGS. Contributed reagents/materials/analysis tools: CLR EMC RGS PCL. Wrote the paper: BGA NP RGS EMC CLR KWF PCL.

                Article
                PONE-D-16-05527
                10.1371/journal.pone.0157891
                4944933
                27416032
                aa026fbb-c055-4f37-a0b0-15b424f634ae

                This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.

                History
                : 7 February 2016
                : 5 June 2016
                Page count
                Figures: 5, Tables: 3, Pages: 14
                Funding
                Funded by: Pediatric Society of North America
                Award Recipient :
                Funded by: National Institute on Aging, National Institutes of Health, Intramural Research Program.
                Award Recipient :
                This work was supported by a Pediatric Society of North America ( https://posna.org/) Grant to CLR, "Identification of Skin Abnormalities in OI Patients by MR Imaging" and the National Institute on Aging, National Institutes of Health, Intramural Research Program (RGS). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Medicine and Health Sciences
                Rheumatology
                Connective Tissue Diseases
                Collagen Diseases
                Osteogenesis Imperfecta
                Medicine and Health Sciences
                Diagnostic Medicine
                Diagnostic Radiology
                Magnetic Resonance Imaging
                Research and Analysis Methods
                Imaging Techniques
                Diagnostic Radiology
                Magnetic Resonance Imaging
                Medicine and Health Sciences
                Radiology and Imaging
                Diagnostic Radiology
                Magnetic Resonance Imaging
                Biology and Life Sciences
                Biochemistry
                Proteins
                Collagens
                Medicine and Health Sciences
                Surgical and Invasive Medical Procedures
                Biopsy
                Biology and Life Sciences
                Anatomy
                Integumentary System
                Skin
                Dermis
                Medicine and Health Sciences
                Anatomy
                Integumentary System
                Skin
                Dermis
                Biology and Life Sciences
                Anatomy
                Integumentary System
                Skin
                Medicine and Health Sciences
                Anatomy
                Integumentary System
                Skin
                Biology and Life Sciences
                Anatomy
                Histology
                Medicine and Health Sciences
                Anatomy
                Histology
                Research and Analysis Methods
                Mathematical and Statistical Techniques
                Statistical Methods
                Multivariate Analysis
                Physical Sciences
                Mathematics
                Statistics (Mathematics)
                Statistical Methods
                Multivariate Analysis
                Custom metadata
                The MRI parameter sets are available in a supplemental data file. Image data files will be available in a public repository at Figshare ( https://figshare.com/articles/MRI_Parameters_Maps/3427598).

                Uncategorized
                Uncategorized

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