Software-based Detection of Acute Rejection Changes in Face Transplant

Miguel I. Dorante; Branislav Kollar; Marian Bittner; Alice Wang; Yannick Diehm; Sina Foroutanjazi; Neil Parikh; Valentin Haug; Tim M. den Uyl; Bohdan Pomahac

doi:10.1055/s-0041-1733995

Journal of Reconstructive Microsurgery, Table of Contents

J Reconstr Microsurg 2022; 38(05): 420-428
DOI: 10.1055/s-0041-1733995

Original Article

Software-based Detection of Acute Rejection Changes in Face Transplant

Authors

Miguel I. Dorante ‡^*

¹Department of Surgery, Division of Plastic Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts

²Department of Surgery, Division of Plastic and Reconstructive Surgery, Lahey Hospital and Medical Center, Burlington, Massachusetts
Branislav Kollar ‡^*

¹Department of Surgery, Division of Plastic Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts

³Department of Plastic and Hand Surgery, University of Freiburg Medical Center, Medical Faculty of the University of Freiburg, Freiburg, Germany
Marian Bittner

⁴VicarVision, Amsterdam, The Netherlands
Alice Wang

¹Department of Surgery, Division of Plastic Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
Yannick Diehm

¹Department of Surgery, Division of Plastic Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts

⁵Department of Hand, Plastic and Reconstructive Surgery, Microsurgery, Burn Trauma Center, BG Trauma Center Ludwigshafen, University of Heidelberg, Ludwigshafen, Germany
Sina Foroutanjazi

¹Department of Surgery, Division of Plastic Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
Neil Parikh

¹Department of Surgery, Division of Plastic Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
Valentin Haug

¹Department of Surgery, Division of Plastic Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts

⁵Department of Hand, Plastic and Reconstructive Surgery, Microsurgery, Burn Trauma Center, BG Trauma Center Ludwigshafen, University of Heidelberg, Ludwigshafen, Germany
Tim M. den Uyl

⁴VicarVision, Amsterdam, The Netherlands
Bohdan Pomahac

¹Department of Surgery, Division of Plastic Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts

⁶Department of Surgery, Division of Plastic and Reconstructive Surgery, Yale New Haven Hospital, Yale School of Medicine, New Haven, Connecticut

Abstract

Background An objective, non-invasive method for redness detection during acute allograft rejection in face transplantation (FT) is lacking.

Methods A retrospective cohort study was performed with 688 images of 7 patients with face transplant (range, 1 to 108 months post-transplant). Healthy controls were matched to donor age, sex, and had no prior facial procedures. Rejection state was confirmed via tissue biopsy. An image-analysis software developed alongside VicarVision (Amsterdam, Netherlands) was used to produce R, a measure of differences between detectable color and absolute red. R is inversely proportional to redness, where lower R values correspond to increased redness. Linear mixed models were used to study fixed effect of rejection state on R values. Estimated marginal means of fitted models were calculated for pairwise comparisons.

Results Of 688 images, 175, 170, 202, and 141 images were attributable to Banff Grade 0,1,2, and 3, respectively. Estimated change in R value of facial allografts decreased with increasing Banff Grade (p = 0.0001). The mean R value of clinical rejection (Banff Grade ⅔) (16.67, 95% Confidence Interval [CI] 14.79–18.58) was lower (p = 0.005) than non-rejection (Banff Grade 0/1) (19.38, 95%CI 17.43–21.33). Both clinical and non-rejection mean R values were lower (p = 0.0001) than healthy controls (24.12, 95%CI 20.96–27.28).

Conclusion This proof-of-concept study demonstrates that software-based analysis can detect and monitor acute rejection changes in FT. Future studies should expand on this tool's potential application in telehealth and as a screening tool for allograft rejection.

Keywords

vascularized composite allotransplantation - face transplant - rejection - software - facial recognition

Full Text

References

References
1 Shores JT, Brandacher G, Lee WPA. Hand and upper extremity transplantation: an update of outcomes in the worldwide experience. Plast Reconstr Surg 2015; 135 (02) 351e-360e
2 Shores JT, Malek V, Lee WPA, Brandacher G. Outcomes after hand and upper extremity transplantation. J Mater Sci Mater Med 2017; 28 (05) 72
3 Sosin M, Rodriguez ED. The Face Transplantation Update: 2016. Plast Reconstr Surg 2016; 137 (06) 1841-1850
4 Kollar B, Pomahac B. Facial restoration by transplantation. Surgeon 2018; 16 (04) 245-249
5 Fischer S, Lian CG, Kueckelhaus M. et al. Acute rejection in vascularized composite allotransplantation. Curr Opin Organ Transplant 2014; 19 (06) 531-544
6 Kueckelhaus M, Fischer S, Seyda M. et al. Vascularized composite allotransplantation: current standards and novel approaches to prevent acute rejection and chronic allograft deterioration. Transpl Int 2016; 29 (06) 655-662
7 Haug V, Kollar B, Obed D. et al. The Evolving Clinical Presentation of Acute Rejection in Facial Transplantation. JAMA Facial Plast Surg 2019; 21 (04) 278-285
8 Tasigiorgos S, Kollar B, Turk M. et al. Five-Year Follow-up after Face Transplantation. N Engl J Med 2019; 380 (26) 2579-2581
9 Petruzzo P, Sardu C, Lanzetta M. et al. Report (2017) of the International Registry on Hand and Composite Tissue Allotransplantation (IRHCTT). Curr Transpl Rep 2017; 4: 294-303
10 Schneider M, Cardones ARG, Selim MA, Cendales LC. Vascularized composite allotransplantation: a closer look at the banff working classification. Transpl Int 2016; 29 (06) 663-671
11 Kueckelhaus M, Fischer S, Lian CG. et al. Utility of sentinel flaps in assessing facial allograft rejection. Plast Reconstr Surg 2015; 135 (01) 250-258
12 Kollar B, Uffing A, Borges TJ. et al. MMP3 Is a Non-invasive Biomarker of Rejection in Skin-Bearing Vascularized Composite Allotransplantation: A Multicenter Validation Study. Front Immunol 2019; 10: 2771
13 Honeyman C, Stark H, Wang HC, Hester J, Issa F, Giele H. Biomarker and surrogate development in vascularised composite allograft transplantation: Current progress and future challenges. J Plast Reconstr Aesthet Surg 2021; 74 (04) 711-717
14 Logger JGM, de Jong EMGJ, Driessen RJB, van Erp PEJ. Evaluation of a simple image-based tool to quantify facial erythema in rosacea during treatment. Skin Res Technol 2020; 26 (06) 804-812
15 Fischer S, Diehm Y, Dorante MI. et al. Software-based video analysis of functional outcomes of face transplantation. Microsurgery 2019; 39 (01) 53-61
16 Dorante MI, Kollar B, Obed D, Haug V, Fischer S, Pomahac B. Recognizing Emotional Expression as an Outcome Measure After Face Transplant. JAMA Netw Open 2020; 3 (01) e1919247
17 Haug V, Kuang Y, Tasigiorgos S. et al. Circulating Donor-derived Cell-free DNA as a Biomarker in Vascularized Composite Allotransplantation?. Transplantation 2020; 104 (03) e79-e80
18 Kueckelhaus M, Imanzadeh A, Fischer S. et al. Noninvasive Monitoring of Immune Rejection in Face Transplant Recipients. Plast Reconstr Surg 2015; 136 (05) 1082-1089
19 Bettoni J, Balédent O, Petruzzo P. et al. Role of flow magnetic resonance imaging in the monitoring of facial allotransplantations: preliminary results on graft vasculopathy. Int J Oral Maxillofac Surg 2020; 49 (02) 169-175
20 Rabbani PS, Rifkin WJ, Kadle RL. et al. Noninvasive Monitoring of Allograft Rejection Using a Novel Epidermal Sampling Technique. Plast Reconstr Surg Glob Open 2019; 7 (08) e2368
21 Lalkhen AG, McCluskey A. Clinical tests: sensitivity and specificity. Contin Educ Anaesth Crit Care Pain 2008; 8 (06) 221-223
22 Kollar B, Pomahac B, Riella LV. Novel immunological and clinical insights in vascularized composite allotransplantation. Curr Opin Organ Transplant 2019; 24 (01) 42-48
23 Kollar B, Shubin A, Borges TJ. et al. Increased levels of circulating MMP3 correlate with severe rejection in face transplantation. Sci Rep 2018; 8 (01) 14915
24 Daneshgaran G, Stern CS, Garfein ES. Reporting Practices on Immunosuppression and Rejection Management in Face Transplantation: A Systematic Review. J Reconstr Microsurg 2019; 35 (09) 652-661
25 Kanitakis J. The challenge of dermatopathological diagnosis of composite tissue allograft rejection: a review. J Cutan Pathol 2008; 35 (08) 738-744
26 Pomahac B, Pribaz J, Eriksson E. et al. Restoration of facial form and function after severe disfigurement from burn injury by a composite facial allograft. Am J Transplant 2011; 11 (02) 386-393
27 Robbins NL, Wordsworth MJ, Parida BK. et al. Is Skin the Most Allogenic Tissue in Vascularized Composite Allotransplantation and a Valid Monitor of the Deeper Tissues?. Plast Reconstr Surg 2019; 143 (04) 880e-886e
28 Sarhane KA, Tuffaha SH, Broyles JM. et al. A critical analysis of rejection in vascularized composite allotransplantation: clinical, cellular and molecular aspects, current challenges, and novel concepts. Front Immunol 2013; 4: 406
29 Yan D, Stokar E, Jacoby A, Gelb BE, Rodriguez ED, Meehan SA. A case of facial composite tissue allograft rejection. JAAD Case Rep 2020; 6 (09) 845-847
30 Kollar B, Rizzo NM, Borges TJ. et al. Accelerated chronic skin changes without allograft vasculopathy: A 10-year outcome report after face transplantation. Surgery 2020; 167 (06) 991-998
31 Kollar B, Kamat P, Klein HJ, Waldner M, Schweizer R, Plock JA. The Significance of Vascular Alterations in Acute and Chronic Rejection for Vascularized Composite Allotransplantation. J Vasc Res 2019; 56 (04) 163-180
32 Kaufman CL, Kanitakis J, Weissenbacher A. et al. Defining chronic rejection in vascularized composite allotransplantation-The American Society of Reconstructive Transplantation and International Society of Vascularized Composite Allotransplantation chronic rejection working group: 2018 American Society of Reconstructive Transplantation meeting report and white paper Research goals in defining chronic rejection in vascularized composite allotransplantation. SAGE Open Med 2020; 8: 2050312120940421
33 Salehi PP, Torabi SJ, Lee YH, Azizzadeh B. Telemedicine Practices of Facial Plastic and Reconstructive Surgeons in the United States: The Effect of Novel Coronavirus-19. Facial Plast Surg Aesthet Med 2020; 22 (06) 464-470
34 Rifkin WJ, Manjunath A, Kimberly LL. et al. Long-distance care of face transplant recipients in the United States. J Plast Reconstr Aesthet Surg 2018; 71 (10) 1383-1391
35 Lambooy S, Krishnasamy R, Pollock A, Hilder G, Gray NA. Telemedicine for Outpatient Care of Kidney Transplant and CKD Patients. Kidney Int Rep 2021; 6 (05) 1265-1272
36 Chang JH, Diop M, Burgos YL. et al. Telehealth in outpatient management of kidney transplant recipients during COVID-19 pandemic in New York. Clin Transplant 2020; 34 (12) e14097
37 Wolfe EM, Najera-Sweeney G, Berman ZP. et al. Establishing Photographic Standards for Facial Transplantation: A Systematic Review of the Literature. Plast Reconstr Surg Glob Open 2020; 8 (05) e2834
38 Liu X, Langsdon S, Holloway W. et al. The Ethics of Facial Allotransplantation: A Systematic Review. Plast Reconstr Surg Glob Open 2019; 7 (10) e2425
39 Kimberly LL, Ramly EP, Alfonso AR, Diep GK, Berman ZP, Rodriguez ED. Equity in access to facial transplantation. J Med Ethics . Published online October 15, 2020:medethics-2020–106129
40 Shokri T, Saadi R, Wang W, Reddy L, Ducic Y. Facial Transplantation: Complications, Outcomes, and Long-Term Management Strategies. Semin Plast Surg 2020; 34 (04) 245-253
41 Baranoski GVG, Van Leeuwen SR, Chen TF. On the detection of peripheral cyanosis in individuals with distinct levels of cutaneous pigmentation. Annu Int Conf IEEE Eng Med Biol Soc 2017; 2017: 4260-4264
42 Kauke M, Panayi AC, Tchiloemba B. et al. Face Transplantation in a Black Patient - Racial Considerations and Early Outcomes. N Engl J Med 2021; 384 (11) 1075-1076
43 Haider AH, Scott VK, Rehman KA. et al. Racial disparities in surgical care and outcomes in the United States: a comprehensive review of patient, provider, and systemic factors. J Am Coll Surg 2013; 216 (03) 482-92.e12
44 Ng Y-H, Pankratz VS, Leyva Y. et al. Does Racial Disparity in Kidney Transplant Waitlisting Persist After Accounting for Social Determinants of Health?. Transplantation 2020; 104 (07) 1445-1455
45 Kernodle AB, Zhang W, Motter JD. et al. Examination of Racial and Ethnic Differences in Deceased Organ Donation Ratio Over Time in the US. JAMA Surg 2021; 156 (04) e207083
46 Ramly EP, Berman ZP, Diep GK, Alfonso AR, Kimberly LL, Rodriguez ED. Vascularized Composite Allotransplantation in a Post-COVID-19 Pandemic World. Plast Reconstr Surg 2020; 146 (03) 394e-395e
47 Dorante MI, Wang A, Kollar B. et al. American Society for Reconstructive Transplantation Conference Abstracts 2020: Emotions after face transplant: first international face transplant cohort comparison. SAGE Open Med 2021; 9: 9
48 Zarins U. Anatomy of Facial Expressions. 2018
49 Guarin DL, Yunusova Y, Taati B. et al. Toward an Automatic System for Computer-Aided Assessment in Facial Palsy. Facial Plast Surg Aesthet Med 2020; 22 (01) 42-49