{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T17:01:45Z","timestamp":1789146105831,"version":"build-2803163510"},"reference-count":17,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,7,16]],"date-time":"2021-07-16T00:00:00Z","timestamp":1626393600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,7,16]],"date-time":"2021-07-16T00:00:00Z","timestamp":1626393600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Musculoskelet Disord"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Familial hypercholesterolemia is a genetic condition characterized by life-long elevations of plasma low-density lipoprotein cholesterol. In addition to life-threatening cardiovascular complications, intratendinous cholesterol deposits (xanthomas) can lead to pain and tendon thickening, particularly in the Achilles. Clinical detection of xanthomas currently relies upon visual assessment and palpation, or ultrasound-based measures of tendon thickening or echotexture. Misdiagnosis of xanthoma can delay the commencement of potentially life-saving lipid-lowering therapy. Our primary purpose was to determine whether analysis of separated fat and water magnetic resonance images may be able to differentiate between xanthomatic and nonxanthomatic Achilles tendons through quantification of intratendinous fat content. The main hypothesis was that Achilles tendon xanthomas will demonstrate greater lipid content than Achilles tendinopathy or healthy control tendons.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Bilateral MRI scans of Achilles tendons from 30 participants (n\u2009=\u200910 Achilles tendon xanthoma, n\u2009=\u200910 Achilles overuse tendinopathy, n\u2009=\u200910 healthy controls) were analyzed for total lipid content using the Dixon method of fat and water signal separation. Secondary outcome measures included tendon water content, as well as ultrasound characterization of tendon tissue organization and thickness.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Fat content was greater in Achilles tendon xanthomas compared to the tendinopathy (p\u2009&lt;\u20090.0001) and control groups (p\u2009&lt;\u20090.0001). Water content was also greater in Achilles tendon xanthomas compared to the tendinopathy (p\u2009&lt;\u20090.0001) and control groups (p\u2009=\u20090.0002). Ultrasound tissue characterization revealed worse tissue organization in Achilles tendon xanthoma tendons compared to Achilles tendinopathy (p\u2009&lt;\u20090.05) but demonstrated largely overlapping distributions. Achilles tendon xanthoma tendons were, on average, significantly thicker than the tendons of the other two groups (p\u2009&lt;\u20090.01 and p\u2009&lt;\u20090.001, respectively).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>MRI-derived measures of Achilles tendon fat content may be able to distinguish xanthomas from control and tendinopathic tissue. Dixon method MRI warrants further evaluation in an adequately powered study to develop and test clinically relevant diagnostic thresholds.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12891-021-04494-0","type":"journal-article","created":{"date-parts":[[2021,7,16]],"date-time":"2021-07-16T20:02:31Z","timestamp":1626465751000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Can Achilles tendon xanthoma be distinguished from Achilles tendinopathy using Dixon method MRI? A cross-sectional exploratory study"],"prefix":"10.1186","volume":"22","author":[{"given":"Thomas Michael","family":"Zahradnik","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Cresswell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kip","family":"Squier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlotte","family":"Waugh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liam","family":"Brunham","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hazel","family":"Screen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex","family":"Scott","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,7,16]]},"reference":[{"issue":"2","key":"4494_CR1","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1016\/j.amjcard.2011.03.027","volume":"108","author":"A Elis","year":"2011","unstructured":"Elis A, Zhou R, Stein EA. Effect of lipid-lowering treatment on natural history of heterozygous familial hypercholesterolemia in past three decades. Am J Cardiol. 2011;108(2):223\u20136.","journal-title":"Am J Cardiol."},{"issue":"1","key":"4494_CR2","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1016\/j.jacl.2018.10.013","volume":"13","author":"A Scott","year":"2019","unstructured":"Scott A, Zahradnik TM, Squier K, Beck C, Brunham LR. Diagnostic accuracy of ultrasound and MRI for Achilles tendon xanthoma in people with familial hypercholesterolemia: A systematic review. J Clin Lipidol. 2019;13(1):40\u20138.","journal-title":"J Clin Lipidol."},{"key":"4494_CR3","doi-asserted-by":"crossref","unstructured":"Beeharry D, Coupe B, Benbow EW, Morgan J, Kwok S, Charlton-Menys V, et al. Familial hypercholesterolaemia commonly presents with Achilles tenosynovitis.\u00a0Ann Rheum Dis.\u00a02006;65(3):312\u20135.","DOI":"10.1136\/ard.2005.040766"},{"key":"4494_CR4","unstructured":"Raju J, Norris J, Gaida J, Cook J, O\u2019Neill S. Development and validation of the VISA-A(sedentary) questionnaire: a modified version of the VISA-A for nonathletic patients with Achilles tendinopathy. Online J Rural Nurs Health Care.\u00a02017;17(1):S15."},{"key":"4494_CR5","doi-asserted-by":"crossref","unstructured":"Outwater EK, Blasbalg R, Siegelman ES, Vala M. Detection of lipid in abdominal tissues with opposed-phase gradient-echo images at 1.5 T: techniques and diagnostic importance. Radiographics.\u00a01998;18(6):1465\u201380.","DOI":"10.1148\/radiographics.18.6.9821195"},{"issue":"6","key":"4494_CR6","doi-asserted-by":"publisher","first-page":"1366","DOI":"10.1007\/s00330-014-3121-1","volume":"24","author":"MA Fischer","year":"2014","unstructured":"Fischer MA, Pfirrmann CW, Espinosa N, Raptis DA, Buck FM. Dixon-based MRI for assessment of muscle-fat content in phantoms, healthy volunteers and patients with achillodynia: comparison to visual assessment of calf muscle quality. Eur Radiol. 2014;24(6):1366\u201375.","journal-title":"Eur Radiol."},{"issue":"1","key":"4494_CR7","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/S0021-9150(02)00330-1","volume":"168","author":"D Marks","year":"2003","unstructured":"Marks D, Thorogood M, Neil HA, Humphries SE. A review on the diagnosis, natural history, and treatment of familial hypercholesterolaemia. Atherosclerosis. 2003;168(1):1\u201314.","journal-title":"Atherosclerosis."},{"issue":"16","key":"4494_CR8","doi-asserted-by":"publisher","first-page":"1153","DOI":"10.1136\/bjsm.2009.061010","volume":"44","author":"HT van Schie","year":"2010","unstructured":"van Schie HT, de Vos RJ, de Jonge S, Bakker EM, Heijboer MP, Verhaar JA, et al. Ultrasonographic tissue characterisation of human Achilles tendons: quantification of tendon structure through a novel non-invasive approach. Br J Sports Med. 2010;44(16):1153\u20139.","journal-title":"Br J Sports Med."},{"key":"4494_CR9","unstructured":"Youngblom E, Pariani M, Knowles JW. Familial Hypercholesterolemia. Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Mirzaa G, et al., editors. Seattle (WA): University of Washington, Seattle. GeneReviews is a registered trademark of the University of Washington, Seattle. All rights reserved; 1993. (GeneReviews((R)))."},{"issue":"4","key":"4494_CR10","doi-asserted-by":"publisher","first-page":"236","DOI":"10.1111\/j.1365-2362.2005.01484.x","volume":"35","author":"SG Tsouli","year":"2005","unstructured":"Tsouli SG, Kiortsis DN, Argyropoulou MI, Mikhailidis DP, Elisaf MS. Pathogenesis, detection and treatment of Achilles tendon xanthomas. Eur J Clin Invest. 2005;35(4):236\u201344.","journal-title":"Eur J Clin Invest."},{"issue":"20","key":"4494_CR11","doi-asserted-by":"publisher","first-page":"4503","DOI":"10.1016\/j.febslet.2005.06.087","volume":"579","author":"M Artieda","year":"2005","unstructured":"Artieda M, Cenarro A, Junquera C, Lasierra P, Martinez-Lorenzo MJ, Pocovi M, et al. Tendon xanthomas in familial hypercholesterolemia are associated with a differential inflammatory response of macrophages to oxidized LDL. FEBS Lett. 2005;579(20):4503\u201312.","journal-title":"FEBS Lett."},{"issue":"45","key":"4494_CR12","doi-asserted-by":"publisher","first-page":"3478","DOI":"10.1093\/eurheartj\/eht273","volume":"34","author":"BG Nordestgaard","year":"2013","unstructured":"Nordestgaard BG, Chapman MJ, Humphries SE, Ginsberg HN, Masana L, Descamps OS, et al. Familial hypercholesterolaemia is underdiagnosed and undertreated in the general population: guidance for clinicians to prevent coronary heart disease: consensus statement of the European Atherosclerosis Society. Eur Heart J. 2013;34(45):3478\u201390.","journal-title":"Eur Heart J."},{"issue":"3","key":"4494_CR13","doi-asserted-by":"publisher","first-page":"876","DOI":"10.1148\/radiol.2017161435","volume":"285","author":"JF Griffith","year":"2017","unstructured":"Griffith JF, Hu M, Yeung DKW, Guo P, Lam SL, Xiao F, et al. Achilles Tendon Xanthomas: Fat-Water Separation at Baseline and after Treatment. Radiology. 2017;285(3):876\u201384.","journal-title":"Radiology."},{"issue":"3 Suppl","key":"4494_CR14","doi-asserted-by":"publisher","first-page":"S1","DOI":"10.1016\/j.jacl.2011.04.003","volume":"5","author":"AC Goldberg","year":"2011","unstructured":"Goldberg AC, Hopkins PN, Toth PP, Ballantyne CM, Rader DJ, Robinson JG, et al. Familial hypercholesterolemia: screening, diagnosis and management of pediatric and adult patients: clinical guidance from the National Lipid Association Expert Panel on Familial Hypercholesterolemia. J Clin Lipidol. 2011;5(3 Suppl):S1-8.","journal-title":"J Clin Lipidol."},{"key":"4494_CR15","doi-asserted-by":"crossref","unstructured":"Bhatnagar D, Morgan J, Siddiq S, Mackness MI, Miller JP, Durrington PN. Outcome of case finding among relatives of patients with known heterozygous familial hypercholesterolaemia. BMJ.\u00a02000;321(7275):1497\u2013500.","DOI":"10.1136\/bmj.321.7275.1497"},{"key":"4494_CR16","doi-asserted-by":"crossref","unstructured":"Koivunen-Niemela T, Komu M, Viikari J, Alanen A. Magnetic resonance imaging of Achilles tendon xanthomas using a fat-water discrimination technique at 0.1 T.\u00a0Acad Radiol.\u00a01995;2(4):319\u201323.","DOI":"10.1016\/S1076-6332(05)80192-8"},{"key":"4494_CR17","unstructured":"Leyendecker JR, Brown JJ, Merkle EM. Practiceal guide to abdominal and pelvic MRI. Philadelphia: Lippincott Williams & Wilkins; 2010."}],"container-title":["BMC Musculoskeletal Disorders"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12891-021-04494-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12891-021-04494-0\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12891-021-04494-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,7,16]],"date-time":"2021-07-16T20:02:47Z","timestamp":1626465767000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcmusculoskeletdisord.biomedcentral.com\/articles\/10.1186\/s12891-021-04494-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7,16]]},"references-count":17,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,12]]}},"alternative-id":["4494"],"URL":"https:\/\/doi.org\/10.1186\/s12891-021-04494-0","relation":{},"ISSN":["1471-2474"],"issn-type":[{"value":"1471-2474","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,7,16]]},"assertion":[{"value":"31 March 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 June 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 July 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Ethical approval was obtained from the University of British Columbia\u2019s Clinical Research Ethics Board (H16-01358) and informed consent was obtained from all participants.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"All authors declare that they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"627"}}