Noninvasive detection of ischemic vascular damage in a pig model of liver donation after circulatory death

Katherine J.I. Ember; Fiona Hunt; Lauren E. Jamieson; John M. Hallett; Hannah Esser; Timothy J. Kendall; R. Eddie Clutton; Rachael Gregson; Karen Faulds; Stuart J. Forbes; Gabriel C. Oniscu; Colin J. Campbell

doi:10.1002/hep.31701

Noninvasive detection of ischemic vascular damage in a pig model of liver donation after circulatory death

Katherine J.I. Ember, Fiona Hunt, Lauren E. Jamieson, John M. Hallett, Hannah Esser, Timothy J. Kendall, R. Eddie Clutton, Rachael Gregson, Karen Faulds, Stuart J. Forbes, Gabriel C. Oniscu, Colin J. Campbell^*

^*Corresponding author for this work

Pure And Applied Chemistry

Research output: Contribution to journal › Article › peer-review

8 Citations (Scopus)

48 Downloads (Pure)

Abstract

Background and Aims: Liver graft quality is evaluated by visual inspection prior to transplantation, a process highly dependent on the surgeon's experience. We present an objective, noninvasive, quantitative way of assessing liver quality in real time using Raman spectroscopy, a laser-based tool for analyzing biomolecular composition. Approach and Results: A porcine model of donation after circulatory death (DCD) with normothermic regional perfusion (NRP) allowed assessment of liver quality premortem, during warm ischemia (WI) and post-NRP. Ten percent of circulating blood volume was removed in half of experiments to simulate blood recovery for DCD heart removal. Left median lobe biopsies were obtained before circulatory arrest, after 45 minutes of WI, and after 2 hours of NRP and analyzed using spontaneous Raman spectroscopy, stimulated Raman spectroscopy (SRS), and staining. Measurements were also taken in situ from the porcine liver using a handheld Raman spectrometer at these time points from left median and right lateral lobes. Raman microspectroscopy detected congestion during WI by measurement of the intrinsic Raman signal of hemoglobin in red blood cells (RBCs), eliminating the need for exogenous labels. Critically, this microvascular damage was not observed during WI when 10% of circulating blood was removed before cardiac arrest. Two hours of NRP effectively cleared RBCs from congested livers. Intact RBCs were visualized rapidly at high resolution using SRS. Optical properties of ischemic livers were significantly different from preischemic and post-NRP livers as measured using a handheld Raman spectrometer. Conclusions: Raman spectroscopy is an effective tool for detecting microvascular damage which could assist the decision to use marginal livers for transplantation. Reducing the volume of circulating blood before circulatory arrest in DCD may help reduce microvascular damage.

Original language	English
Pages (from-to)	428-443
Number of pages	16
Journal	Hepatology
Volume	74
Issue number	1
Early online date	8 Jan 2021
DOIs	https://doi.org/10.1002/hep.31701
Publication status	Published - 31 Jul 2021

Funding

Thanks to Bertrand Vernay for assistance with QuPath cell counting, Mike Millar of QMRI SURF imaging facility, and members of the Forbes, Campbell, and Faulds labs, especially Janet Man, Sarah McAughtrie, and Amy Morrison. Thanks to Steve Wigmore of the Royal Infirmary of Edinburgh for assistance in application for the Confidence in Concept grant. Thank you to the Royal (Dick) School of Veterinary Sciences, especially Timothy King for help with the pig transplant experiments. Thanks also to Henri Leuvenink and Leonie Venema of Groeningen University and Arjan van der Plaats, chief technology officer at Organ Assist, the Netherlands.

Keywords

noninvasive
detection
ischemic vascular damage
pig
model
liver donation
circulatory death

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10.1002/hep.31701Licence: CC BY 4.0

Ember-etal-Hepatology-2020-Noninvasive-detection-of-ischemic-vascular-damageFinal published version, 2.08 MBLicence: CC BY 4.0

Cite this

@article{4d2d24e990914baba357515054edb329,

title = "Noninvasive detection of ischemic vascular damage in a pig model of liver donation after circulatory death",

abstract = "Background and Aims: Liver graft quality is evaluated by visual inspection prior to transplantation, a process highly dependent on the surgeon's experience. We present an objective, noninvasive, quantitative way of assessing liver quality in real time using Raman spectroscopy, a laser-based tool for analyzing biomolecular composition. Approach and Results: A porcine model of donation after circulatory death (DCD) with normothermic regional perfusion (NRP) allowed assessment of liver quality premortem, during warm ischemia (WI) and post-NRP. Ten percent of circulating blood volume was removed in half of experiments to simulate blood recovery for DCD heart removal. Left median lobe biopsies were obtained before circulatory arrest, after 45 minutes of WI, and after 2 hours of NRP and analyzed using spontaneous Raman spectroscopy, stimulated Raman spectroscopy (SRS), and staining. Measurements were also taken in situ from the porcine liver using a handheld Raman spectrometer at these time points from left median and right lateral lobes. Raman microspectroscopy detected congestion during WI by measurement of the intrinsic Raman signal of hemoglobin in red blood cells (RBCs), eliminating the need for exogenous labels. Critically, this microvascular damage was not observed during WI when 10% of circulating blood was removed before cardiac arrest. Two hours of NRP effectively cleared RBCs from congested livers. Intact RBCs were visualized rapidly at high resolution using SRS. Optical properties of ischemic livers were significantly different from preischemic and post-NRP livers as measured using a handheld Raman spectrometer. Conclusions: Raman spectroscopy is an effective tool for detecting microvascular damage which could assist the decision to use marginal livers for transplantation. Reducing the volume of circulating blood before circulatory arrest in DCD may help reduce microvascular damage.",

keywords = "noninvasive, detection, ischemic vascular damage, pig, model, liver donation, circulatory death",

author = "Ember, {Katherine J.I.} and Fiona Hunt and Jamieson, {Lauren E.} and Hallett, {John M.} and Hannah Esser and Kendall, {Timothy J.} and Clutton, {R. Eddie} and Rachael Gregson and Karen Faulds and Forbes, {Stuart J.} and Oniscu, {Gabriel C.} and Campbell, {Colin J.}",

year = "2021",

month = jul,

day = "31",

doi = "10.1002/hep.31701",

language = "English",

volume = "74",

pages = "428--443",

journal = "Hepatology",

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TY - JOUR

T1 - Noninvasive detection of ischemic vascular damage in a pig model of liver donation after circulatory death

AU - Ember, Katherine J.I.

AU - Hunt, Fiona

AU - Jamieson, Lauren E.

AU - Hallett, John M.

AU - Esser, Hannah

AU - Kendall, Timothy J.

AU - Clutton, R. Eddie

AU - Gregson, Rachael

AU - Faulds, Karen

AU - Forbes, Stuart J.

AU - Oniscu, Gabriel C.

AU - Campbell, Colin J.

PY - 2021/7/31

Y1 - 2021/7/31

N2 - Background and Aims: Liver graft quality is evaluated by visual inspection prior to transplantation, a process highly dependent on the surgeon's experience. We present an objective, noninvasive, quantitative way of assessing liver quality in real time using Raman spectroscopy, a laser-based tool for analyzing biomolecular composition. Approach and Results: A porcine model of donation after circulatory death (DCD) with normothermic regional perfusion (NRP) allowed assessment of liver quality premortem, during warm ischemia (WI) and post-NRP. Ten percent of circulating blood volume was removed in half of experiments to simulate blood recovery for DCD heart removal. Left median lobe biopsies were obtained before circulatory arrest, after 45 minutes of WI, and after 2 hours of NRP and analyzed using spontaneous Raman spectroscopy, stimulated Raman spectroscopy (SRS), and staining. Measurements were also taken in situ from the porcine liver using a handheld Raman spectrometer at these time points from left median and right lateral lobes. Raman microspectroscopy detected congestion during WI by measurement of the intrinsic Raman signal of hemoglobin in red blood cells (RBCs), eliminating the need for exogenous labels. Critically, this microvascular damage was not observed during WI when 10% of circulating blood was removed before cardiac arrest. Two hours of NRP effectively cleared RBCs from congested livers. Intact RBCs were visualized rapidly at high resolution using SRS. Optical properties of ischemic livers were significantly different from preischemic and post-NRP livers as measured using a handheld Raman spectrometer. Conclusions: Raman spectroscopy is an effective tool for detecting microvascular damage which could assist the decision to use marginal livers for transplantation. Reducing the volume of circulating blood before circulatory arrest in DCD may help reduce microvascular damage.

AB - Background and Aims: Liver graft quality is evaluated by visual inspection prior to transplantation, a process highly dependent on the surgeon's experience. We present an objective, noninvasive, quantitative way of assessing liver quality in real time using Raman spectroscopy, a laser-based tool for analyzing biomolecular composition. Approach and Results: A porcine model of donation after circulatory death (DCD) with normothermic regional perfusion (NRP) allowed assessment of liver quality premortem, during warm ischemia (WI) and post-NRP. Ten percent of circulating blood volume was removed in half of experiments to simulate blood recovery for DCD heart removal. Left median lobe biopsies were obtained before circulatory arrest, after 45 minutes of WI, and after 2 hours of NRP and analyzed using spontaneous Raman spectroscopy, stimulated Raman spectroscopy (SRS), and staining. Measurements were also taken in situ from the porcine liver using a handheld Raman spectrometer at these time points from left median and right lateral lobes. Raman microspectroscopy detected congestion during WI by measurement of the intrinsic Raman signal of hemoglobin in red blood cells (RBCs), eliminating the need for exogenous labels. Critically, this microvascular damage was not observed during WI when 10% of circulating blood was removed before cardiac arrest. Two hours of NRP effectively cleared RBCs from congested livers. Intact RBCs were visualized rapidly at high resolution using SRS. Optical properties of ischemic livers were significantly different from preischemic and post-NRP livers as measured using a handheld Raman spectrometer. Conclusions: Raman spectroscopy is an effective tool for detecting microvascular damage which could assist the decision to use marginal livers for transplantation. Reducing the volume of circulating blood before circulatory arrest in DCD may help reduce microvascular damage.

KW - noninvasive

KW - detection

KW - ischemic vascular damage

KW - pig

KW - model

KW - liver donation

KW - circulatory death

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U2 - 10.1002/hep.31701

DO - 10.1002/hep.31701

M3 - Article

C2 - 33420756

AN - SCOPUS:85107865855

SN - 0270-9139

VL - 74

SP - 428

EP - 443

JO - Hepatology

JF - Hepatology

IS - 1

ER -

Noninvasive detection of ischemic vascular damage in a pig model of liver donation after circulatory death

Abstract

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Development of Imaging Technologies for 3D Visualisation of Cancer Invasion (EPSRC OPTIMA)

EPSRC Centre for Doctoral Training in Optical Medical Imaging - Training the next generation of scientific entrepreneurs in healthcare technologies (OPTIMA)

University Of Strathclyde - Equipment Account

Cite this

Noninvasive detection of ischemic vascular damage in a pig model of liver donation after circulatory death

Abstract

Funding

Keywords

Access to Document

Other files and links

Fingerprint

Projects

Development of Imaging Technologies for 3D Visualisation of Cancer Invasion (EPSRC OPTIMA)

EPSRC Centre for Doctoral Training in Optical Medical Imaging - Training the next generation of scientific entrepreneurs in healthcare technologies (OPTIMA)

University Of Strathclyde - Equipment Account

Cite this