Abstract 2559: Reflectance, Fluorescence, and Raman Spectroscopy Identify Features of Vulnerable Atherosclerotic Plaque In Vivo Including a Thin Fibrous Cap, Necrotic Core or Superficial Foam Cells, and Thrombus

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Obrad R Šćepanović ◽  
Maryann Fitzmaurice ◽  
Arnold Miller ◽  
Chae-Ryon Kong ◽  
Ramachandra R Dasari ◽  
...  
Keyword(s):  
Raman Spectroscopy ◽  
Early Detection ◽  
Ex Vivo ◽  
Foam Cells ◽  
Necrotic Core ◽  
Histopathological Analysis ◽  
Artery Wall ◽  
Fibrous Cap ◽  
Vulnerable Plaques

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.

scholarly journals Applications of Vibrational Spectroscopy for Analysis of Connective Tissues

Molecules ◽  
2021 ◽  
Vol 26 (4) ◽  
pp. 922
Author(s):  
William Querido ◽  
Shital Kandel ◽  
Nancy Pleshko
Keyword(s):  
Raman Spectroscopy ◽  
Vibrational Spectroscopy ◽  
Near Infrared ◽  
Ex Vivo ◽  
Biological Tissues ◽  
Label Free ◽  
Connective Tissues ◽  
Bone Properties ◽  
Composition And Structure

Advances in vibrational spectroscopy have propelled new insights into the molecular composition and structure of biological tissues. In this review, we discuss common modalities and techniques of vibrational spectroscopy, and present key examples to illustrate how they have been applied to enrich the assessment of connective tissues. In particular, we focus on applications of Fourier transform infrared (FTIR), near infrared (NIR) and Raman spectroscopy to assess cartilage and bone properties. We present strengths and limitations of each approach and discuss how the combination of spectrometers with microscopes (hyperspectral imaging) and fiber optic probes have greatly advanced their biomedical applications. We show how these modalities may be used to evaluate virtually any type of sample (ex vivo, in situ or in vivo) and how “spectral fingerprints” can be interpreted to quantify outcomes related to tissue composition and quality. We highlight the unparalleled advantage of vibrational spectroscopy as a label-free and often nondestructive approach to assess properties of the extracellular matrix (ECM) associated with normal, developing, aging, pathological and treated tissues. We believe this review will assist readers not only in better understanding applications of FTIR, NIR and Raman spectroscopy, but also in implementing these approaches for their own research projects.

scholarly journals EANM recommendations based on systematic analysis of small animal radionuclide imaging in inflammatory musculoskeletal diseases

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Erik H. J. G. Aarntzen ◽  
Edel Noriega-Álvarez ◽  
Vera Artiko ◽  
André H. Dias ◽  
Olivier Gheysens ◽  
...  
Keyword(s):  
Molecular Imaging ◽  
Radionuclide Imaging ◽  
Musculoskeletal Diseases ◽  
Ex Vivo ◽  
Imaging Techniques ◽  
Large Body ◽  
Therapeutic Interventions ◽  
Histopathological Analysis ◽  
Complementary Value

AbstractInflammatory musculoskeletal diseases represent a group of chronic and disabling conditions that evolve from a complex interplay between genetic and environmental factors that cause perturbations in innate and adaptive immune responses. Understanding the pathogenesis of inflammatory musculoskeletal diseases is, to a large extent, derived from preclinical and basic research experiments. In vivo molecular imaging enables us to study molecular targets and to measure biochemical processes non-invasively and longitudinally, providing information on disease processes and potential therapeutic strategies, e.g. efficacy of novel therapeutic interventions, which is of complementary value next to ex vivo (post mortem) histopathological analysis and molecular assays. Remarkably, the large body of preclinical imaging studies in inflammatory musculoskeletal disease is in contrast with the limited reports on molecular imaging in clinical practice and clinical guidelines. Therefore, in this EANM-endorsed position paper, we performed a systematic review of the preclinical studies in inflammatory musculoskeletal diseases that involve radionuclide imaging, with a detailed description of the animal models used. From these reflections, we provide recommendations on what future studies in this field should encompass to facilitate a greater impact of radionuclide imaging techniques on the translation to clinical settings.

Simultaneous Fingerprint and High-Wavenumber Confocal Raman Spectroscopy Enhances Early Detection of Cervical Precancer In Vivo

2012 ◽  
Vol 84 (14) ◽  
pp. 5913-5919 ◽  
Author(s):  
Shiyamala Duraipandian ◽  
Wei Zheng ◽  
Joseph Ng ◽  
Jeffrey J.H. Low ◽  
A. Ilancheran ◽  
...  
Keyword(s):  
Raman Spectroscopy ◽  
Early Detection ◽  
Confocal Raman Spectroscopy ◽  
Cervical Precancer ◽  
Confocal Raman

scholarly journals Ratiometric analysis using Raman spectroscopy as a powerful predictor of structural properties of fatty acids

2018 ◽  
Vol 5 (12) ◽  
pp. 181483 ◽  
Author(s):  
Lauren E. Jamieson ◽  
Angela Li ◽  
Karen Faulds ◽  
Duncan Graham
Keyword(s):  
Fatty Acids ◽  
Raman Spectroscopy ◽  
Biological Sample ◽  
Ex Vivo ◽  
Degree Of Saturation ◽  
Specific Information ◽  
Analytical Technique ◽  
Starting Point

Raman spectroscopy has been used extensively for the analysis of biological samples in vitro , ex vivo and in vivo . While important progress has been made towards using this analytical technique in clinical applications, there is a limit to how much chemically specific information can be extracted from a spectrum of a biological sample, which consists of multiple overlapping peaks from a large number of species in any particular sample. In an attempt to elucidate more specific information regarding individual biochemical species, as opposed to very broad assignments by species class, we propose a bottom-up approach beginning with a detailed analysis of pure biochemical components. Here, we demonstrate a simple ratiometric approach applied to fatty acids, a subsection of the lipid class, to allow the key structural features, in particular degree of saturation and chain length, to be predicted. This is proposed as a starting point for allowing more chemically and species-specific information to be elucidated from the highly multiplexed spectrum of multiple overlapping signals found in a real biological sample. The power of simple ratiometric analysis is also demonstrated by comparing the prediction of degree of unsaturation in food oil samples using ratiometric and multivariate analysis techniques which could be used for food oil authentication.

Assessment of ex-vivo and in-vivo near-infrared Raman spectroscopy for the classification of dysplasia within Barrett's esophagus

2000 ◽  
Author(s):  
Martin G. Shim ◽  
Louis-Michel Wong Kee Song ◽  
Norman E. Marcon ◽  
Shirley Hassaram ◽  
Brian C. Wilson
Keyword(s):  
Raman Spectroscopy ◽  
Barrett’S Esophagus ◽  
Barrett's Esophagus ◽  
Near Infrared ◽  
Ex Vivo

Stress Concentrations of Vulnerable Plaques With a Composite Variable Core

2010 ◽  
Author(s):  
Eyass Massarwa ◽  
Aronis Ze’ev ◽  
Rami Eliasy ◽  
Rami Haj-Ali ◽  
Shmuel Einav
Keyword(s):  
Plaque Rupture ◽  
Necrotic Core ◽  
Intraplaque Hemorrhage ◽  
Plaque Morphology ◽  
Rapid Progression ◽  
Stress Concentrations ◽  
Coronary Syndrome ◽  
Fibrous Cap ◽  
Vulnerable Plaques ◽  
Life Threatening

Vulnerable plaques are inflamed, active, and growing lesions which are prone to complications such as rupture, luminal and mural thrombosis, intraplaque hemorrhage, and rapid progression to stenosis. It remains difficult to assess what factors influence the biomechanical stability of vulnerable plaques and promote some of them to rupture while others remain intact. The rupture of thin fibrous cap overlying the necrotic core of a vulnerable plaque is the principal cause of acute coronary syndrome. The mechanism or mechanisms responsible for the sudden conversion of a stable atherosclerotic plaque to a life threatening athero-thrombotic lesion are not fully understood. It has been widely assumed that plaque morphology is the major determinant of clinical outcome [1, 2]. Thin-cap fibroatheroma with a large necrotic core and a fibrous cap of < 65μm was describes as a more specific precursor of plaque rupture due to tissue stress.

Abstract T MP29: Contrast-Enhanced Ultrasound is Useful for Detection of Vulnerable Plaques

Stroke ◽  
2015 ◽  
Vol 46 (suppl_1) ◽  
Author(s):  
Rie Motoyama ◽  
Kozue Saito ◽  
Shuichi Tonomura ◽  
Hatsue I Ueda ◽  
Hiroharu Kataoka ◽  
...  
Keyword(s):  
High Intensity ◽  
Necrotic Core ◽  
Intraplaque Hemorrhage ◽  
Contrast Enhanced Ultrasound ◽  
Histopathological Findings ◽  
Rapid Acquisition ◽  
Fibrous Cap ◽  
Vulnerable Plaques ◽  
Contrast Enhanced ◽  
Active Inflammation

Background and Purpose: Vulnerable plaques of carotid arteries are characterized as the presence of large necrotic core, intraplaque hemorrhage (IPH), intraplaque neovascularization (IPN), and active inflammation with thin fibrous cap. MRI is widely used for the qualitative evaluation of the plaques in vivo and the high-intensity plaques (HIP) on magnetization-prepared rapid acquisition with gradient echo (MPRAGE) images indicate containing necrotic cores with IPH, which indicates vulnerable plaques. However, we encounter the symptomatic cases without the presence of HIP on MPRAGE in clinical practice. Recent studies showed the efficacy for the evaluation of IPN using contrast-enhanced ultrasound (CEUS). We aimed to assess the vulnerability of the plaques without high intensity on MPRAGE images using CEUS. Methods: Between July 2010 and June 2014, we enrolled 69 patients with internal carotid artery stenosis who underwent carotid endarterectomy (CEA) and preoperatively examined CEUS and MRI (MPRAGE). All plaques were evaluated with CEUS and the contrast effects were classified semi-quantitatively (grade 0: absent, 1: small, 2: large, 3: extensive). We also divided the plaques into two groups (HIP group or non-HIP group) based on the signal intensity of the plaques on MPRAGE images. The results of MRI and CEUS were compared with histopathological findings of CEA specimens. Results: Fifty-eight plaques of all 69 patients showed HIP (41 were symptomatic), and eleven plaques were non-HIP (five were symptomatic: amaurosis fugax in three, cerebral infarction in two). In non-HIP group, symptomatic plaques were more enhanced (three in grade 2, two in grade 3) than asymptomatic plaques (one in grade 0, five in grade 1) using CEUS. Histopathological findings of all five CEA specimens from symptomatic patients showed that extensive IPN, large necrotic core, and active inflammation with thin fibrous cap which indicated vulnerable plaques, but small amount of IPH. These histological findings were compatible with the results of CEUS and MRI findings. Conclusion: CEUS may be useful for diagnosis of vulnerable plaques without high intensity on MPRAGE images.

Abstract 17216: Intracoronary Dual-modal OCT/NIRF Structural-Molecular Imaging with a Clinical Dose of Indocyanine Green (ICG) for Detection of High-risk Coronary Plaques in Diabetic Swine Model

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Sunwon Kim ◽  
Min Woo Lee ◽  
Han Saem Cho ◽  
Joon Woo Song ◽  
Sunki Lee ◽  
...  
Keyword(s):  
High Risk ◽  
Near Infrared ◽  
Ex Vivo ◽  
Swine Model ◽  
Fully Integrated ◽  
Coronary Syndrome ◽  
Fibrous Cap ◽  
Nirf Imaging

Background: Acute coronary syndrome is frequently caused by rupture of macrophage abundant plaques with a large lipid-rich core. The present study aimed to investigate whether a fully integrated OCT/NIRF imaging combined with a clinically available near-infrared fluorescence (NIRF) enhancing ICG can detect the inflamed, lipid-rich plaques in swine coronary atheromata whose phenotype is similar to human vulnerable fibroatheroma. Methods and Results: Accelerated atherosclerosis was made by coronary balloon denudation in alloxan induced diabetic minipigs. A rapid coronary imaging (20 mm/sec pullback speed) using a fully integrated OCT/NIRF catheter was safely performed 30 minutes after I.V. injection of ICG (2.0 mg/kg) just under contrast purge. OCT clearly identified the lipid-rich plaques with fibrous cap. Simultaneously acquired, distance-calibrated NIRF imaging detected lipid-laden macrophage signals in OCT-proven plaques (figure). The in vivo plaque target-to-background ratio (pTBR) was significantly higher in ICG-injected swine compared to non-diabetic swines or saline-injected controls (p<0.05), which was validated on ex vivo fluorescence reflectance imaging (FRI) (figure). The in vivo and ex vivo peak pTBRs correlated significantly (p<0.05). In vitro experiments, and histopathology including fluorescence microscopic imaging and immunostaining of the plaque sections corroborated the findings in vivo . Conlusions: An OCT/NIRF imaging with a clinical use of ICG accurately identified macrophage abundant, lipid-rich coronary plaques in diabetic atheromatous minipigs. This highly translatable dual-modal molecular-structural imaging could be relevant for clinical intracoronary detection of high-risk plaques.

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