Optical-resolution photoacoustic microscopy continually
monitors macrophages activities of acute
inflammation in vivo
Fei Duan (段 飞)
1,†
, Haosong Ma (马浩淞)
1,†
, Jinde Zhang (张锦德)
1
, Shi Li (李 实)
1
,
Honghui Li (李宏辉)
1
, Zhiyou Wu (吴志友)
1
, Fengqiu Hong (洪凤秋)
1
,
Lüming Zeng (曾吕明)
2,3
, and Liming Nie (聂立铭)
1,
*
1
State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics & Center for Molecular Imaging and
Translational Medicine, School of Public Health, Xiamen University, Xiamen 361102, China
2
State Key Laboratory of Precision Electronic Manufacturing Technology and Equipment, School of Electromechanical
Engineering, Guangdong University of Technology, Guangzhou 510006, China
3
Jiangxi Key Laboratory of Optic-Electronic and Communication, Jiangxi Science and Technology
Normal University, Nanchang 330038, China
*Corresponding author: nielm@xmu.edu.cn
Received June 18, 2020; accepted August 10, 2020; posted online September 25, 2020
Photoacoustic imaging has been developed to image the immune study at the macro scale. Macrophages play
diverse roles in the acute response to infection and tissue repair. However, macrophages activities in acute in-
flammation at the microscopic level still remain challenging. In this work, we proposed optical-resolution photo-
acoustic microscopy to promptly monitor the labeled macrophages activities in normal and inflammatory
groups. The result showed that many labeled macrophages emerged around the vessels firstly, then exuded into
tissues, and finally disappeared in the inflammatory group injected with labeled macrophages. In summary, our
method allows us to exactly image and track the immune cells of inflammatory diseases.
Keywords: photoacoustic microscopy; macrophages activities; vessel parameter.
doi: 10.3788/COL202018.121701.
Macrophages are a heterogeneous population of resident
and recruited cells that are found in all organs
[1]
, which
are an important part of the mononuclear phagocyte sys-
tem to maintain the stability of the immune system
[2]
.
Macrophages also play a critical role in tissue repair and
remodeling, as well as in the orchestration of the host’s
response to infectious diseases through secretion of cyto-
kines, enzymes, and reactive oxygen species
[1]
. They can
display significant plasticity and change their physiology
according to environmental cues to produce different cell
populations with different functions
[3]
. In the process of
inflammation, macrophages are activated and involved
in the autoregulatory loop of inflammation. Their main
role is to produce a variety of cytokines and growth factors
for antigen presentation, phagocytosis, and immune
regulation
[4]
.
Now, in vivo clinical imaging tools for noninvasive mac-
rophage quantification are expected to predict patients’
clinical outcome, define treatment options, and monitor
therapy responses
[5]
. But, imaging the immune cells still
focuses on the preclinical study that is limited by the tech-
nique development. Optical imaging offers exceptional op-
portunities to visualize and quantify multiple dynamic
events in living cells with high resolution
[6]
. Fluorescence
imaging as a conventional optical imaging technique
has opened the possibility of generating bespoke reagents
to image cellular activity in real time
[7–9]
. However, the
limited penetration depth of confocal and two-photon
microscopy usually requires skin surgery during imag-
ing
[10]
. Moreover, long-term observation of most fluores-
cent dyes is not realistic because of photo-bleaching
[11]
.
As a new non-destructive imaging method, photoacous-
tic (PA) imaging has been widely used in biomedical
research, such as brain disease
[12,13]
. The scale of PA imag-
ing extends from organelles, cells, tissues, and organs to
the whole body
[14]
. Optical-resolution PA microscopy
(OR-PAM) has high spatial resolution and large penetra-
tion depth. Now, it has many different forms, for example,
the portable OR-PAM was used in stomatology
[15]
. The
blind-deconvolution OR-PAM can provide a lateral reso-
lution ∼2-fold finer than that of conventional OR-PAM
[16]
.
OR-PAM has been applied to different biomedical appli-
cations, such as monitoring vascular normalization during
anti-angiogenic therapy
[17]
, imaging early-stage nanocarrier-
enhanced chemotherapy response in living subjects
[18]
,and
assessing the burn healing
[19]
. It was used to monitor the
vessels in inflammation induced by lipopolysaccharide
[20]
.
Micro-electro mechanical system (MEMS)-OR-PAM as
a rapid imaging technique was also used to monitor the ves-
sel changes
[21]
. PA imaging was used to image the immune
cells labeled with silica-coated nanorods
[22]
and the immune
cell activities at the macro scale
[23]
. But, these studies did not
involve any immune cell activities at the microscopic level to
the best of our knowledge.
In this study, we set up an OR-PAM system and fur-
ther employed the MEMS technique for fast imaging.
COL 18(12), 121701(2020) CHINESE OPTICS LETTERS December 2020
1671-7694/2020/121701(5) 121701-1 © 2020 Chinese Optics Letters