Early detection of heterotopic ossification using near-infrared optical imaging reveals dynamic turnover and progression of mineralization following Achilles tenotomy and burn injury
ABSTRACT Heterotopic ossification (HO) is the abnormal formation of bone in soft tissue. Current diagnostics have low sensitivity or specificity to incremental progression of mineralization, especially at early time points. Without accurate and reliable early diagnosis and intervention, HO progressi...
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| Veröffentlicht in: | Journal of orthopaedic research 2014-11, Vol.32 (11), p.1416-1423 |
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| creator | Perosky, Joseph E. Peterson, Jonathan R. Eboda, Owulatobi N. Morris, Michael D. Wang, Stewart C. Levi, Benjamin Kozloff, Kenneth M. |
| description | ABSTRACT
Heterotopic ossification (HO) is the abnormal formation of bone in soft tissue. Current diagnostics have low sensitivity or specificity to incremental progression of mineralization, especially at early time points. Without accurate and reliable early diagnosis and intervention, HO progression often results in incapacitating conditions of limited range of motion, nerve entrapment, and pain. We hypothesized that non‐invasive near‐infrared (NIR) optical imaging can detect HO at early time points and monitor heterotopic bone turnover longitudinally. C57BL6 mice received an Achilles tenotomy on their left hind limb in combination with a dorsal burn or sham procedure. A calcium‐chelating tetracycline derivative (IRDye 680RD BoneTag) was injected bi‐weekly and imaged via NIR to measure accumulative fluorescence for 11 wk and compared to in vivo microCT images. Percent retention of fluorescence was calculated longitudinally to assess temporal bone resorption. NIR detected HO as early as five days and revealed a temporal response in HO formation and turnover. MicroCT could not detect HO until 5 wk. Confocal microscopy confirmed fluorophore localization to areas of HO. These findings demonstrate the ability of a near‐infrared optical imaging strategy to accurately and reliably detect and monitor HO in a murine model. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 32:1416–1423, 2014. |
| doi_str_mv | 10.1002/jor.22697 |
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Heterotopic ossification (HO) is the abnormal formation of bone in soft tissue. Current diagnostics have low sensitivity or specificity to incremental progression of mineralization, especially at early time points. Without accurate and reliable early diagnosis and intervention, HO progression often results in incapacitating conditions of limited range of motion, nerve entrapment, and pain. We hypothesized that non‐invasive near‐infrared (NIR) optical imaging can detect HO at early time points and monitor heterotopic bone turnover longitudinally. C57BL6 mice received an Achilles tenotomy on their left hind limb in combination with a dorsal burn or sham procedure. A calcium‐chelating tetracycline derivative (IRDye 680RD BoneTag) was injected bi‐weekly and imaged via NIR to measure accumulative fluorescence for 11 wk and compared to in vivo microCT images. Percent retention of fluorescence was calculated longitudinally to assess temporal bone resorption. NIR detected HO as early as five days and revealed a temporal response in HO formation and turnover. MicroCT could not detect HO until 5 wk. Confocal microscopy confirmed fluorophore localization to areas of HO. These findings demonstrate the ability of a near‐infrared optical imaging strategy to accurately and reliably detect and monitor HO in a murine model. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 32:1416–1423, 2014.</description><identifier>ISSN: 0736-0266</identifier><identifier>EISSN: 1554-527X</identifier><identifier>DOI: 10.1002/jor.22697</identifier><identifier>PMID: 25087685</identifier><language>eng</language><publisher>United States: Blackwell Publishing Ltd</publisher><subject>Achilles Tendon - diagnostic imaging ; Achilles Tendon - physiopathology ; Animals ; biomarkers ; Biomarkers - metabolism ; Bone and Bones - diagnostic imaging ; Bone Resorption ; Burns - physiopathology ; Calcium - chemistry ; Chelating Agents - chemistry ; Contrast Media - chemistry ; Disease Progression ; Fluorescent Dyes - chemistry ; heterotopic Ossification ; Male ; Mice ; Mice, Inbred C57BL ; microCT ; Microscopy, Confocal ; molecular imaging ; Ossification, Heterotopic - diagnostic imaging ; Ossification, Heterotopic - physiopathology ; Range of Motion, Articular ; Sensitivity and Specificity ; Spectroscopy, Near-Infrared ; Tenotomy ; Tetracycline - chemistry ; X-Ray Microtomography</subject><ispartof>Journal of orthopaedic research, 2014-11, Vol.32 (11), p.1416-1423</ispartof><rights>2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.</rights><rights>2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. 2014</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5237-47f0015fbb6a23267cd79037dad59430ea38d2bb93ab9d8430ae7088524a13ca3</citedby><cites>FETCH-LOGICAL-c5237-47f0015fbb6a23267cd79037dad59430ea38d2bb93ab9d8430ae7088524a13ca3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fjor.22697$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fjor.22697$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>230,314,780,784,885,1416,1432,27923,27924,45573,45574,46408,46832</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25087685$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Perosky, Joseph E.</creatorcontrib><creatorcontrib>Peterson, Jonathan R.</creatorcontrib><creatorcontrib>Eboda, Owulatobi N.</creatorcontrib><creatorcontrib>Morris, Michael D.</creatorcontrib><creatorcontrib>Wang, Stewart C.</creatorcontrib><creatorcontrib>Levi, Benjamin</creatorcontrib><creatorcontrib>Kozloff, Kenneth M.</creatorcontrib><title>Early detection of heterotopic ossification using near-infrared optical imaging reveals dynamic turnover and progression of mineralization following Achilles tenotomy and burn injury</title><title>Journal of orthopaedic research</title><addtitle>J. Orthop. Res</addtitle><description>ABSTRACT
Heterotopic ossification (HO) is the abnormal formation of bone in soft tissue. Current diagnostics have low sensitivity or specificity to incremental progression of mineralization, especially at early time points. Without accurate and reliable early diagnosis and intervention, HO progression often results in incapacitating conditions of limited range of motion, nerve entrapment, and pain. We hypothesized that non‐invasive near‐infrared (NIR) optical imaging can detect HO at early time points and monitor heterotopic bone turnover longitudinally. C57BL6 mice received an Achilles tenotomy on their left hind limb in combination with a dorsal burn or sham procedure. A calcium‐chelating tetracycline derivative (IRDye 680RD BoneTag) was injected bi‐weekly and imaged via NIR to measure accumulative fluorescence for 11 wk and compared to in vivo microCT images. Percent retention of fluorescence was calculated longitudinally to assess temporal bone resorption. NIR detected HO as early as five days and revealed a temporal response in HO formation and turnover. MicroCT could not detect HO until 5 wk. Confocal microscopy confirmed fluorophore localization to areas of HO. These findings demonstrate the ability of a near‐infrared optical imaging strategy to accurately and reliably detect and monitor HO in a murine model. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 32:1416–1423, 2014.</description><subject>Achilles Tendon - diagnostic imaging</subject><subject>Achilles Tendon - physiopathology</subject><subject>Animals</subject><subject>biomarkers</subject><subject>Biomarkers - metabolism</subject><subject>Bone and Bones - diagnostic imaging</subject><subject>Bone Resorption</subject><subject>Burns - physiopathology</subject><subject>Calcium - chemistry</subject><subject>Chelating Agents - chemistry</subject><subject>Contrast Media - chemistry</subject><subject>Disease Progression</subject><subject>Fluorescent Dyes - chemistry</subject><subject>heterotopic Ossification</subject><subject>Male</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>microCT</subject><subject>Microscopy, Confocal</subject><subject>molecular imaging</subject><subject>Ossification, Heterotopic - diagnostic imaging</subject><subject>Ossification, Heterotopic - physiopathology</subject><subject>Range of Motion, Articular</subject><subject>Sensitivity and Specificity</subject><subject>Spectroscopy, Near-Infrared</subject><subject>Tenotomy</subject><subject>Tetracycline - chemistry</subject><subject>X-Ray Microtomography</subject><issn>0736-0266</issn><issn>1554-527X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kcFu1DAQhi0EosvCgRdAPsIhrWPHcXJBqqpul6pqpQoEN8tJJrteHHuxky3hwXg-vJt2BQdOlv3_882Mf4TepuQ0JYSebZw_pTQvxTM0SznPEk7Ft-doRgTLE0Lz_AS9CmFDCBEpLV6iE8pJIfKCz9DvS-XNiBvooe61s9i1eB0v3vVuq2vsQtCtrtVBG4K2K2xB-UTb1isPDXbbPsoG606t9qqHHSgTcDNa1UVAP3jrduCxsg3eerfyEJFTo05b8MroXxO-dca4hz3kvF5rYyDgHmwcpBsP1VVEYW03gx9foxdt7AJvHs85-rK4_HyxTG7urj5dnN8kNadMJJloCUl5W1W5oozmom5ESZhoVMPLjBFQrGhoVZVMVWVTxBcFghQFp5lKWa3YHH2cuNuh6qCpwfZxYLn1cV0_Sqe0_Fexei1XbiezjBQlyyLg_SPAux8DhF52OtRgjLLghiBTnudpyrNonqMPk7X28dc9tMc2KZH7nGXMWR5yjt53f891dD4FGw1nk-FBGxj_T5LXd_dPyGSq0KGHn8cK5b_LXDDB5dfbK7m4Xi7LYnEvb9kfIEzI5A</recordid><startdate>201411</startdate><enddate>201411</enddate><creator>Perosky, Joseph E.</creator><creator>Peterson, Jonathan R.</creator><creator>Eboda, Owulatobi N.</creator><creator>Morris, Michael D.</creator><creator>Wang, Stewart C.</creator><creator>Levi, Benjamin</creator><creator>Kozloff, Kenneth M.</creator><general>Blackwell Publishing Ltd</general><scope>BSCLL</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>201411</creationdate><title>Early detection of heterotopic ossification using near-infrared optical imaging reveals dynamic turnover and progression of mineralization following Achilles tenotomy and burn injury</title><author>Perosky, Joseph E. ; Peterson, Jonathan R. ; Eboda, Owulatobi N. ; Morris, Michael D. ; Wang, Stewart C. ; Levi, Benjamin ; Kozloff, Kenneth M.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5237-47f0015fbb6a23267cd79037dad59430ea38d2bb93ab9d8430ae7088524a13ca3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Achilles Tendon - diagnostic imaging</topic><topic>Achilles Tendon - physiopathology</topic><topic>Animals</topic><topic>biomarkers</topic><topic>Biomarkers - metabolism</topic><topic>Bone and Bones - diagnostic imaging</topic><topic>Bone Resorption</topic><topic>Burns - physiopathology</topic><topic>Calcium - chemistry</topic><topic>Chelating Agents - chemistry</topic><topic>Contrast Media - chemistry</topic><topic>Disease Progression</topic><topic>Fluorescent Dyes - chemistry</topic><topic>heterotopic Ossification</topic><topic>Male</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>microCT</topic><topic>Microscopy, Confocal</topic><topic>molecular imaging</topic><topic>Ossification, Heterotopic - diagnostic imaging</topic><topic>Ossification, Heterotopic - physiopathology</topic><topic>Range of Motion, Articular</topic><topic>Sensitivity and Specificity</topic><topic>Spectroscopy, Near-Infrared</topic><topic>Tenotomy</topic><topic>Tetracycline - chemistry</topic><topic>X-Ray Microtomography</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Perosky, Joseph E.</creatorcontrib><creatorcontrib>Peterson, Jonathan R.</creatorcontrib><creatorcontrib>Eboda, Owulatobi N.</creatorcontrib><creatorcontrib>Morris, Michael D.</creatorcontrib><creatorcontrib>Wang, Stewart C.</creatorcontrib><creatorcontrib>Levi, Benjamin</creatorcontrib><creatorcontrib>Kozloff, Kenneth M.</creatorcontrib><collection>Istex</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Journal of orthopaedic research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Perosky, Joseph E.</au><au>Peterson, Jonathan R.</au><au>Eboda, Owulatobi N.</au><au>Morris, Michael D.</au><au>Wang, Stewart C.</au><au>Levi, Benjamin</au><au>Kozloff, Kenneth M.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Early detection of heterotopic ossification using near-infrared optical imaging reveals dynamic turnover and progression of mineralization following Achilles tenotomy and burn injury</atitle><jtitle>Journal of orthopaedic research</jtitle><addtitle>J. Orthop. Res</addtitle><date>2014-11</date><risdate>2014</risdate><volume>32</volume><issue>11</issue><spage>1416</spage><epage>1423</epage><pages>1416-1423</pages><issn>0736-0266</issn><eissn>1554-527X</eissn><abstract>ABSTRACT
Heterotopic ossification (HO) is the abnormal formation of bone in soft tissue. Current diagnostics have low sensitivity or specificity to incremental progression of mineralization, especially at early time points. Without accurate and reliable early diagnosis and intervention, HO progression often results in incapacitating conditions of limited range of motion, nerve entrapment, and pain. We hypothesized that non‐invasive near‐infrared (NIR) optical imaging can detect HO at early time points and monitor heterotopic bone turnover longitudinally. C57BL6 mice received an Achilles tenotomy on their left hind limb in combination with a dorsal burn or sham procedure. A calcium‐chelating tetracycline derivative (IRDye 680RD BoneTag) was injected bi‐weekly and imaged via NIR to measure accumulative fluorescence for 11 wk and compared to in vivo microCT images. Percent retention of fluorescence was calculated longitudinally to assess temporal bone resorption. NIR detected HO as early as five days and revealed a temporal response in HO formation and turnover. MicroCT could not detect HO until 5 wk. Confocal microscopy confirmed fluorophore localization to areas of HO. These findings demonstrate the ability of a near‐infrared optical imaging strategy to accurately and reliably detect and monitor HO in a murine model. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 32:1416–1423, 2014.</abstract><cop>United States</cop><pub>Blackwell Publishing Ltd</pub><pmid>25087685</pmid><doi>10.1002/jor.22697</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Achilles Tendon - diagnostic imaging Achilles Tendon - physiopathology Animals biomarkers Biomarkers - metabolism Bone and Bones - diagnostic imaging Bone Resorption Burns - physiopathology Calcium - chemistry Chelating Agents - chemistry Contrast Media - chemistry Disease Progression Fluorescent Dyes - chemistry heterotopic Ossification Male Mice Mice, Inbred C57BL microCT Microscopy, Confocal molecular imaging Ossification, Heterotopic - diagnostic imaging Ossification, Heterotopic - physiopathology Range of Motion, Articular Sensitivity and Specificity Spectroscopy, Near-Infrared Tenotomy Tetracycline - chemistry X-Ray Microtomography |
| title | Early detection of heterotopic ossification using near-infrared optical imaging reveals dynamic turnover and progression of mineralization following Achilles tenotomy and burn injury |
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