2526:利用热成像技术在大型血管化复合异体移植动物模型中无创监测同种异体移植排斥反应

K. Kolegraff, A. Quan, Nicole J. Crane, Howard D. Wang, Joseph Lopez, G. Furtmuller, Sara AlFadil, S. Mermulla, B. Oh, Paul J. Akre, Jose C. Alonso-Escalante, J. Walch, J. Shores, D. Cooney, S. Bonawitz, E. Elster, G. Brandacher, W. Lee
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Andrew Lee Johns Hopkins University School of Medicine, Baltimore, MD, USA; Naval Medical Research Center, Bethesda, MD, USA; Uniformed Services University of the Health Sciences and Walter Reed National Military Medical Center, Bethesda, MD, USA Background Vascularized composite allotransplantation (VCA), including hand and face transplantation, is increasingly utilized for reconstruction of disfiguring injuries. Immune rejection is a problem inherent to allotransplantation and must be recognized early to prevent graft injury/loss. Skin biopsy is required to confirm rejection however this approach may further promote rejection through tissue injury. Thermal imaging has been used to non-invasively detect inflammation and ischemia in other disease states but has not been evaluated in VCA rejection. The purpose of this study was to evaluate the utility of non-invasive thermal imaging in the detection of rejection in a swine VCAmodel. Methods Osteomyocutaneous hindlimb transplantation was performed in 9 MGH miniature swine across a full SLA mismatch. The positive rejection control group (3 pigs) did not receive any form of immunosuppression. The treated group (6 pigs) received non-myeloablative conditioning with 50cGy total body and 350cGy thymic irradiation prior to transplantation, daily tacrolimus (20–25 ng/ml) until POD 30, and IV steroids on POD 4–6. Allografts were assessed daily for erythema, edema, blistering, and ulceration. Daily infrared images were acquired using a thermal camera (FLIR E8 #63903-0303) and thermal emission intensities from graft and contralateral flank control were analyzed using Image. Results In the untreated group, erythema was observed by POD 4 and progressed to epidermolysis by POD 8 in 3/3 animals. In the treated group, rejection was observed at POD 5–7 in 6/6 animals and was reversed by POD 10 with steroids in 5/6 animals. The sixth animal developed severe rejection on POD 5 that progressed to necrosis despite steroids. Interestingly, infrared imaging did not distinguish these episodes of rejection in the early post-operative period (<POD 30) despite clinical signs of inflammation and biopsyproven rejection (Banff II–IV). At later post-operative periods (>POD 60), there was a trend toward cooler graft temperatures even in the absence of clinical rejection. Conclusions Despite signs of inflammation, infrared imaging did not reliably detect graft rejection. The finding that grafts become cooler over time suggests there may be long-term changes in graft perfusion. This may represent chronic graft injury and is the subject of on-going studies. CONTACT Keli Kolegraff keli@jhmi.edu © 2016 Keli Kolegraff, Amy Quan, Nicole Crane, Howard Wang, Joseph Lopez, Georg Furtmuller, Sara Alfadil, Sara Mermulla, Byoung Chol Oh, Paul Akre, Jose C. Alonso-Escalante, Jeffrey Walch, Jaimie Shores, Damon Cooney, Steven Bonawitz, Eric Elster, Gerald Brandacher, and W. P. Andrew Lee. Published with license by Taylor & Francis. This is an Open Access article distributed under the terms of the Creative Commons Attribution-Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. The moral rights of the named author(s) have been asserted. 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Lee\",\"doi\":\"10.1080/23723505.2016.1234260\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"2526: Non-invasive monitoring of allograft rejection using thermal imaging in a large animal model of vascularized composite allotransplantation Keli Kolegraff, Amy Quan, Nicole Crane, Howard Wang, Joseph Lopez, Georg Furtmuller, Sara Alfadil, Sara Mermulla, Byoung Chol Oh, Paul Akre, Jose C. Alonso-Escalante, Jeffrey Walch, Jaimie Shores, Damon Cooney, Steven Bonawitz, Eric Elster, Gerald Brandacher, and W. P. Andrew Lee Johns Hopkins University School of Medicine, Baltimore, MD, USA; Naval Medical Research Center, Bethesda, MD, USA; Uniformed Services University of the Health Sciences and Walter Reed National Military Medical Center, Bethesda, MD, USA Background Vascularized composite allotransplantation (VCA), including hand and face transplantation, is increasingly utilized for reconstruction of disfiguring injuries. 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Allografts were assessed daily for erythema, edema, blistering, and ulceration. Daily infrared images were acquired using a thermal camera (FLIR E8 #63903-0303) and thermal emission intensities from graft and contralateral flank control were analyzed using Image. Results In the untreated group, erythema was observed by POD 4 and progressed to epidermolysis by POD 8 in 3/3 animals. In the treated group, rejection was observed at POD 5–7 in 6/6 animals and was reversed by POD 10 with steroids in 5/6 animals. The sixth animal developed severe rejection on POD 5 that progressed to necrosis despite steroids. Interestingly, infrared imaging did not distinguish these episodes of rejection in the early post-operative period (<POD 30) despite clinical signs of inflammation and biopsyproven rejection (Banff II–IV). At later post-operative periods (>POD 60), there was a trend toward cooler graft temperatures even in the absence of clinical rejection. Conclusions Despite signs of inflammation, infrared imaging did not reliably detect graft rejection. The finding that grafts become cooler over time suggests there may be long-term changes in graft perfusion. This may represent chronic graft injury and is the subject of on-going studies. CONTACT Keli Kolegraff keli@jhmi.edu © 2016 Keli Kolegraff, Amy Quan, Nicole Crane, Howard Wang, Joseph Lopez, Georg Furtmuller, Sara Alfadil, Sara Mermulla, Byoung Chol Oh, Paul Akre, Jose C. Alonso-Escalante, Jeffrey Walch, Jaimie Shores, Damon Cooney, Steven Bonawitz, Eric Elster, Gerald Brandacher, and W. P. Andrew Lee. Published with license by Taylor & Francis. This is an Open Access article distributed under the terms of the Creative Commons Attribution-Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. 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引用次数: 0

摘要

2526年:在血管化复合异体移植大型动物模型中使用热成像无创伤监测同种异体移植排斥反应的Keli Kolegraff, Amy Quan, Nicole Crane, Howard Wang, Joseph Lopez, Georg Furtmuller, Sara Alfadil, Sara Mermulla, Byoung Chol Oh, Paul Akre, Jose C. Alonso-Escalante, Jeffrey Walch, Jaimie Shores, Damon Cooney, Steven Bonawitz, Eric Elster, Gerald Brandacher和W. P. Andrew Lee约翰霍普金斯大学医学院,巴尔的摩,MD,美国;海军医学研究中心,美国马里兰州贝塞斯达;背景血管化复合异体移植(VCA),包括手部和面部移植,越来越多地用于毁容损伤的重建。免疫排斥反应是同种异体移植的固有问题,必须及早发现以防止移植物损伤/丢失。需要皮肤活检来确认排斥反应,但这种方法可能通过组织损伤进一步促进排斥反应。热成像已用于无创检测其他疾病状态下的炎症和缺血,但尚未对VCA排斥反应进行评估。本研究的目的是评估非侵入性热成像在猪vcam模型中检测排斥反应的效用。方法对9头MGH小型猪进行全SLA不匹配的后肢骨肌皮移植。阳性排斥对照组(3头猪)未接受任何形式的免疫抑制。治疗组(6头猪)在移植前接受全身50cGy和胸腺350cGy的非清髓调节,每日他克莫司(20-25 ng/ml)至POD 30,并在POD 4-6静脉注射类固醇。每天评估同种异体移植物的红斑、水肿、起泡和溃疡。使用热像仪(FLIR E8 #63903-0303)获取每日红外图像,并使用Image分析植片和对侧侧侧对照的热发射强度。结果未经治疗组3/3动物经POD 4检测出现红斑,经POD 8检测进展为表皮松解。在治疗组中,6/6只动物的POD 5-7出现排斥反应,5/6只动物的POD 10加类固醇可以逆转排斥反应。第六只动物出现了严重的POD 5排斥反应,尽管使用类固醇,但仍进展为坏死。有趣的是,红外成像不能区分术后早期的排斥反应(POD 60),即使在没有临床排斥反应的情况下,移植物温度也有降低的趋势。结论:尽管有炎症迹象,但红外成像不能可靠地检测移植排斥反应。移植物随着时间的推移而变冷的发现表明移植物灌注可能存在长期变化。这可能代表慢性移植物损伤,是正在进行的研究的主题。联系Keli Kolegraff keli@jhmi.edu©2016 Keli Kolegraff、Amy Quan、Nicole Crane、Howard Wang、Joseph Lopez、Georg Furtmuller、Sara Alfadil、Sara Mermulla、Byoung Chol Oh、Paul Akre、Jose C. Alonso-Escalante、Jeffrey Walch、Jaimie Shores、Damon Cooney、Steven Bonawitz、Eric Elster、Gerald Brandacher和W. P. Andrew Lee。由Taylor & Francis授权出版。这是一篇在知识共享署名-非商业许可(http://creativecommons.org/licenses/by-nc/3.0/)条款下发布的开放获取文章,该许可允许在任何媒体上不受限制的非商业使用、分发和复制,前提是正确引用原始作品。指定作者的精神权利得到了维护。血管化复合异体移植,2016,VOL. 3, no . 1-2, 39 http://dx.doi.org/10.1080/23723505.2016.1234260
本文章由计算机程序翻译,如有差异,请以英文原文为准。
2526: Non-invasive monitoring of allograft rejection using thermal imaging in a large animal model of vascularized composite allotransplantation
2526: Non-invasive monitoring of allograft rejection using thermal imaging in a large animal model of vascularized composite allotransplantation Keli Kolegraff, Amy Quan, Nicole Crane, Howard Wang, Joseph Lopez, Georg Furtmuller, Sara Alfadil, Sara Mermulla, Byoung Chol Oh, Paul Akre, Jose C. Alonso-Escalante, Jeffrey Walch, Jaimie Shores, Damon Cooney, Steven Bonawitz, Eric Elster, Gerald Brandacher, and W. P. Andrew Lee Johns Hopkins University School of Medicine, Baltimore, MD, USA; Naval Medical Research Center, Bethesda, MD, USA; Uniformed Services University of the Health Sciences and Walter Reed National Military Medical Center, Bethesda, MD, USA Background Vascularized composite allotransplantation (VCA), including hand and face transplantation, is increasingly utilized for reconstruction of disfiguring injuries. Immune rejection is a problem inherent to allotransplantation and must be recognized early to prevent graft injury/loss. Skin biopsy is required to confirm rejection however this approach may further promote rejection through tissue injury. Thermal imaging has been used to non-invasively detect inflammation and ischemia in other disease states but has not been evaluated in VCA rejection. The purpose of this study was to evaluate the utility of non-invasive thermal imaging in the detection of rejection in a swine VCAmodel. Methods Osteomyocutaneous hindlimb transplantation was performed in 9 MGH miniature swine across a full SLA mismatch. The positive rejection control group (3 pigs) did not receive any form of immunosuppression. The treated group (6 pigs) received non-myeloablative conditioning with 50cGy total body and 350cGy thymic irradiation prior to transplantation, daily tacrolimus (20–25 ng/ml) until POD 30, and IV steroids on POD 4–6. Allografts were assessed daily for erythema, edema, blistering, and ulceration. Daily infrared images were acquired using a thermal camera (FLIR E8 #63903-0303) and thermal emission intensities from graft and contralateral flank control were analyzed using Image. Results In the untreated group, erythema was observed by POD 4 and progressed to epidermolysis by POD 8 in 3/3 animals. In the treated group, rejection was observed at POD 5–7 in 6/6 animals and was reversed by POD 10 with steroids in 5/6 animals. The sixth animal developed severe rejection on POD 5 that progressed to necrosis despite steroids. Interestingly, infrared imaging did not distinguish these episodes of rejection in the early post-operative period (POD 60), there was a trend toward cooler graft temperatures even in the absence of clinical rejection. Conclusions Despite signs of inflammation, infrared imaging did not reliably detect graft rejection. The finding that grafts become cooler over time suggests there may be long-term changes in graft perfusion. This may represent chronic graft injury and is the subject of on-going studies. CONTACT Keli Kolegraff keli@jhmi.edu © 2016 Keli Kolegraff, Amy Quan, Nicole Crane, Howard Wang, Joseph Lopez, Georg Furtmuller, Sara Alfadil, Sara Mermulla, Byoung Chol Oh, Paul Akre, Jose C. Alonso-Escalante, Jeffrey Walch, Jaimie Shores, Damon Cooney, Steven Bonawitz, Eric Elster, Gerald Brandacher, and W. P. Andrew Lee. Published with license by Taylor & Francis. This is an Open Access article distributed under the terms of the Creative Commons Attribution-Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. The moral rights of the named author(s) have been asserted. VASCULARIZED COMPOSITE ALLOTRANSPLANTATION 2016, VOL. 3, NOS. 1–2, 39 http://dx.doi.org/10.1080/23723505.2016.1234260
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