In Vivo Quantitative Measurement of Intact Fibrous Cap and Lipid-Rich Necrotic Core Size in Atherosclerotic Carotid Plaque

Early detection and treatment of vulnerable atherosclerotic plaques, the lesions most prone to rupture, is critical to reducing patient mortality associated with cardiovascular disease. The combination of reflectance, fluorescence, and Raman spectroscopy - termed multimodal spectroscopy (MMS) - provides complementary and depth-sensitive information about tissue composition. We assessed the hypothesis that MMS can detect morphological features of vulnerable plaque: thin fibrous cap (TFC), necrotic core (NC), superficial foam cells (SFC), intralesional hemorrhage (IH), and thrombus. Methods. In vivo and ex vivo MMS spectra were collected from 12 patients undergoing peripheral vascular surgeries. The data collection was facilitated by means of a novel MMS probe catheter and a portable clinical instrument developed in our laboratory. During carotid endarterectomies, MMS spectra were collected in vivo from the intimal surface of the plaque with the probe held normal to the artery wall. During femoral bypasses, MMS spectra were collected in vivo either through the proximal anastomosis site from the posterior artery wall or adjacent to the incision. A tissue specimen was excised for additional MMS spectral collection ex vivo. Histopathological analysis was performed by a blinded cardiovascular pathologist to assess the vulnerability of each spectrally evaluated tissue site using a quantitative index based on the dimension or severity of the following: TFC, NC, SFC, IH, and thrombus. Across the total set of 76 evaluated tissue locations, MMS is shown to have the ability to detect vulnerability features including a TFC, NC or SFCs, and thrombus. A TFC is detected by measuring the relative amount of collagen assessed by fluorescence, a large NC or SFCs are detected through the combination of beta-carotene absorption and the Raman spectral signature of lipids, and thrombus is detected through its Raman signature. The results indicate that rupture-prone vulnerable plaques could be detected with a sensitivity of 96% and specificity of 72%. In conclusion, these encouraging results will help bring MMS into the clinical arena as a powerful, catheter-based diagnostic technique for early detection of vulnerable plaques.

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Visualization of Fibrous Cap Thickness and Rupture in Human Atherosclerotic Carotid Plaque In Vivo With High-Resolution Magnetic Resonance Imaging

Circulation ◽

10.1161/01.cir.102.9.959 ◽

2000 ◽

Vol 102 (9) ◽

pp. 959-964 ◽

Cited By ~ 387

Author(s):

Thomas S. Hatsukami ◽

Russell Ross ◽

Nayak L. Polissar ◽

Chun Yuan

Keyword(s):

Magnetic Resonance Imaging ◽

Magnetic Resonance ◽

High Resolution ◽

Carotid Plaque ◽

Resonance Imaging ◽

Fibrous Cap ◽

Fibrous Cap Thickness

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Carotid Plaque Fibrous Cap Thickness Measurement by ARFI Variance of Acceleration: In Vivo Human Results

IEEE Transactions on Medical Imaging ◽

10.1109/tmi.2020.3019184 ◽

2020 ◽

Vol 39 (12) ◽

pp. 4383-4390 ◽

Cited By ~ 2

Author(s):

Gabriela Torres ◽

Tomasz J. Czernuszewicz ◽

Jonathon W. Homeister ◽

Mark A. Farber ◽

Melissa C. Caughey ◽

...

Keyword(s):

Carotid Plaque ◽

Thickness Measurement ◽

Fibrous Cap ◽

Fibrous Cap Thickness

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Can We Use In Vivo MRI and FEA to Determine Peak Cap Stress in Carotid Plaques? MRI Simulations Provide Answers

Volume 1B: Extremity; Fluid Mechanics; Gait; Growth, Remodeling, and Repair; Heart Valves; Injury Biomechanics; Mechanotransduction and Sub-Cellular Biophysics; MultiScale Biotransport; Muscle, Tendon and Ligament; Musculoskeletal Devices; Multiscale Mechanics; Thermal Medicine; Ocular Biomechanics; Pediatric Hemodynamics; Pericellular Phenomena; Tissue Mechanics; Biotransport Design and Devices; Spine; Stent Device Hemodynamics; Vascular Solid Mechanics; Student Paper and Design Competitions ◽

10.1115/sbc2013-14114 ◽

2013 ◽

Author(s):

Harm A. Nieuwstadt ◽

Jolanda W. Wentzel ◽

Aad van der Lugt ◽

Anton F. W. van der Steen ◽

Marcel Breeuwer ◽

...

Keyword(s):

Plaque Rupture ◽

Important Determinant ◽

Peak Stress ◽

Necrotic Core ◽

Rupture Risk ◽

Resonance Imaging ◽

Element Analysis ◽

Fibrous Cap ◽

Magnetic Resonance Imaging Mri

Vulnerable plaques are characterized by a large lipid-rich necrotic core (LRNC) separated by a thin fibrous cap (FC) from the lumen. Plaque rupture occurs when the peak stress in the FC exceeds its strength. Carotid in vivo magnetic resonance imaging (MRI) data can be segmented to obtain the plaque geometry noninvasively. An increasing number of studies use MR imaging for biomechanical finite element analysis (FEA) to compute peak cap stresses [1, 2]. Previous studies have shown that the thickness of the FC is an important determinant of peak cap stress: the thinner the FC, the higher the stress, the higher the plaque rupture risk [3].

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Research on the correlation between activating transcription factor 3 expression in the human coronary artery and atherosclerotic plaque stability

BMC Cardiovascular Disorders ◽

10.1186/s12872-021-02161-9 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

J. Peng ◽

C. Y. Le ◽

B. Xia ◽

J. W. Wang ◽

J. J. Liu ◽

...

Keyword(s):

Coronary Artery ◽

Necrotic Core ◽

Inflammatory Factors ◽

Lesion Group ◽

Control Group ◽

Atherosclerotic Plaques ◽

Activating Transcription Factor 3 ◽

Fibrous Cap ◽

Fibrous Cap Thickness ◽

Activating Transcription Factor

Abstract Background Activating transcription factor 3 (ATF3) is an early response gene that is activated in response to atherosclerotic stimulation and may be an important factor in inhibiting the progression of atherosclerosis. In this study, we directly measured the expression of ATF3 and inflammatory factors in human coronary atherosclerotic plaques to examine the relationship between ATF3 expression, inflammation and structural stability in human coronary atherosclerotic plaques. Methods A total of 68 coronary artery specimens were collected from the autopsy group, including 36 cases of sudden death from coronary heart disease (SCD group) and 32 cases of acute death caused by mechanical injury with coronary atherosclerosis (CHD group). Twenty-two patients who had no coronary heart disease were collected as the control group (Con group). The histological structure of the coronary artery was observed under a light microscope after routine HE staining, and the intimal and lesion thicknesses, thickness of the fibrous cap, thickness of necrosis core, degree of lumen stenosis were assessed by image analysis software. Western blotting and immunohistochemistry were used to measure the expression and distribution of ATF3, inflammatory factors (CD45, IL-1β, TNF-α) and matrix metalloproteinase-9 (MMP-9) and vascular cell adhesion molecule 1 (VCAM1) in the coronary artery. The Pearson correlation coefficient was used to analyse the correlation between ATF3 protein expression and inflammatory factors and between ATF3 protein expression and structure-related indexes in the lesion group. Results Compared with those in the control group, the intima and necrotic core in the coronary artery were thickened, the fibrous cap became thin and the degree of vascular stenosis was increased in the lesion group, while the intima and necrotic core became thicker and the fibrous cap became thinner in the SCD group than in the CHD group (P < 0.05). There was no or low expression of ATF3, inflammatory factors, VCAM1 and MMP-9 in the control group, and the expression of inflammatory factors, VCAM1 and MMP-9 in the SCD group was higher than that in CHD group, while the expression of ATF3 in the SCD group was significantly lower than that in CHD group (P < 0.05). In the lesion group, the expression of ATF3 was negatively correlated with intimal and necrotic focus thickness, positively correlated with fibrous cap thickness (P < 0.01), and negatively correlated with inflammatory factors, VCAM1 and MMP-9 (P < 0.01). Conclusions The expression of ATF3 may be related to the progression and stability of atherosclerotic plaques, and may affect the structural stability of atherosclerotic plaques by regulating the inflammatory response, thus participating in the regulation of atherosclerotic progression.

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Association between White Matter Ischaemia and Carotid Plaque Morphology as Defined by High-resolution In Vivo MRI

European Journal of Vascular and Endovascular Surgery ◽

10.1016/j.ejvs.2009.04.005 ◽

2009 ◽

Vol 38 (2) ◽

pp. 149-154 ◽

Cited By ~ 9

Author(s):

A.J. Patterson ◽

J.M. U-King-Im ◽

T.Y. Tang ◽

D.J. Scoffings ◽

S.P.S. Howarth ◽

...

Keyword(s):

White Matter ◽

High Resolution ◽

Carotid Plaque ◽

Plaque Morphology

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In vivo attenuation and equivalent scatterer size parameters for atherosclerotic carotid plaque: Preliminary results

Ultrasonics ◽

10.1016/j.ultras.2009.06.004 ◽

2009 ◽

Vol 49 (8) ◽

pp. 779-785 ◽

Cited By ~ 18

Author(s):

Hairong Shi ◽

Tomy Varghese ◽

Carol C. Mitchell ◽

Matthew McCormick ◽

Robert J. Dempsey ◽

...

Keyword(s):

Carotid Plaque ◽

Preliminary Results ◽

Scatterer Size

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A Decade of Imaging Cellular Motility and Interaction Dynamics in the Immune System

Science ◽

10.1126/science.1221063 ◽

2012 ◽

Vol 336 (6089) ◽

pp. 1676-1681 ◽

Cited By ~ 235

Author(s):

Ronald N. Germain ◽

Ellen A. Robey ◽

Michael D. Cahalan

Keyword(s):

Lymph Nodes ◽

Live Cell Imaging ◽

Quantitative Measurement ◽

Cell Imaging ◽

Plasma Cells ◽

Effector T Cells ◽

Cellular Interactions ◽

Cellular Motility ◽

Response Dynamics

To mount an immune response, lymphocytes must recirculate between the blood and lymph nodes, recognize antigens upon contact with specialized presenting cells, proliferate to expand a small number of clonally relevant lymphocytes, differentiate to antibody-producing plasma cells or effector T cells, exit from lymph nodes, migrate to tissues, and engage in host-protective activities. All of these processes involve motility and cellular interactions—events that were hidden from view until recently. Introduced to immunology by three papers in this journal in 2002, in vivo live-cell imaging studies are revealing the behavior of cells mediating adaptive and innate immunity in diverse tissue environments, providing quantitative measurement of cellular motility, interactions, and response dynamics. Here, we review themes emerging from such studies and speculate on the future of immunoimaging.

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