Molecular Imaging Technology Research Articles

Noninvasive assessment and therapeutic monitoring of drug-resistant colorectal cancer by MR molecular imaging of extradomain-B fibronectin.

Antineoplastic resistance represents a multifaceted challenge for cancer therapy and diagnostics. Extensive molecular heterogeneity, even within neoplasms of the same type, can elicit distinct outcomes of administering therapeutic pressures, frequently leading to the development of drug-resistant populations. Improved success of oncotherapies merits the exploration of precise molecular imaging technologies that can detect not only anatomical but also molecular changes in tumors and their microenvironment, early on in the treatment regimen. To this end, we developed magnetic resonance molecular imaging (MRMI) strategies to target the extracellular matrix oncoprotein, extradomain-B fibronectin (EDB-FN), for non-invasive assessment and therapeutic monitoring of drug-resistant colorectal cancer (CRC).Methods: Two drug-resistant CRC lines generated from parent DLD-1 and RKO cells by long-term treatment with 5ʹ-FU and 5ʹ-FU plus CB-839 respectively, were characterized for functional and gene expression changes using 3D culture, transwell invasion, qRT-PCR, and western blot assays. Contrast-enhanced MRMI of EDB-FN was performed in athymic nu/nu mice bearing subcutaneous tumor xenografts with 40 µmol/kg dose of macrocyclic ZD2-targeted contrast agent MT218 [ZD2-N3-Gd (HP-DO3A)] on a 3T MRS 3000 scanner. Immunohistochemistry was conducted on patient specimens and xenografts using anti-EDB-FN antibody G4.Results: Analyses of TCGA and GTEx databases revealed poor prognosis of colon cancer patients with higher levels of EDB-FN. Similarly, immunohistochemical staining of patient specimens showed increased EDB-FN expression in primary colon adenocarcinoma and hepatic metastases, but none in normal adjacent tissues. Drug-resistant DLD1-DR and RKO-DR cells were also found to demonstrate enhanced invasive potential and significantly elevated EDB-FN expression over their parent counterparts. MRMI of EDB-FN with 40 µmol/kg dose of MT218 (60% lower than the clinical dose) resulted in robust signal enhancement in the drug-resistant CRC xenografts with 84-120% increase in their contrast-to-noise ratios (CNRs) over the non-resistant counterparts. The feasibility of non-invasive therapeutic monitoring using MRMI of EDB-FN was also evaluated in drug-resistant DLD1-DR tumors treated with a pan-AKT inhibitor MK2206-HCl. The treated drug-resistant tumors failed to respond to therapy, which was accurately detected by MRMI with MT218, demonstrating higher signal enhancement and increased CNRs in the 4-week follow-up scans over the pre-treatment scans.Conclusions: EDB-FN is a promising molecular marker for assessing drug resistance. MRMI of EDB-FN with MT218 at a significantly reduced dose can facilitate effective non-invasive assessment and treatment response monitoring of drug-resistant CRC, highlighting its translational potential for active surveillance and management of CRC and other malignancies.

Molecular Imaging Technology: A Promising Frontier of Interventional Radiology

Various radiological diagnostic processes like x-ray scans, ultrasonography, CT-Scans and MRI Scans are only able to provide the doctors with information regarding the physical structure of organs. In order to analyse and acquire information about what happens at the molecular level molecular imaging modality emerges as the most appropriate technology. It is safe, non-invasive, pain-less and gives the equal information that would have otherwise been obtained by invasive and painful surgeries or biopsies. Beside this, it has innumerable advantages over the other diagnostic imaging techniques ranging from early detection to prediction of reoccurrence. Different types of available molecular imaging models stands out as a detection and therapeutic procedure for health anomalies including cancer and disease related to heart, brain, gastrointestinal, lung, bone, kidney, thyroid etc. This emerging screening tool radiates the same dose of ionizing radiation as any other radiological diagnostic process but it is able to supply a great spectrum of physiological information unlike the other procedures and thus is very efficient and much more precise. In this technique, special types of cameras are used to detect the radiopharmaceuticals that work with computers to provide very precise pictures of the area of the body being imaged. Over the years it is emerging as the ultimate and most sought after diagnostic cum therapeutic procedure because of its efficient and precise contribution in the detection and treatment for cancer and tumours in medical and health research field. Hence, this paper provides an assessment of the efficacy of molecular imaging technology based on its instrumentation and clinical application which is a very promising frontier of interventional radiology.

Recent Advances in quantitative dynamic PET imaging of neuroendocrine tumors

Dynamic positron emission tomography (PET) imaging is a standard art of molecular imaging technology for visualization and quantitative assessment of biochemical and physiopathological activity at cellular and molecular levels in humans and laboratory animals. Tracer kinetic modeling approach developed and validated in last decades is now widely used to extract parameters from dynamic PET data. In the study of neuroendocrine tumors (NETs), the kinetic parameters such as tracer uptake rate constant Ki estimated from dynamic PET with FDA approved 18 F-FDG and 68 Ga-DOTATATE tracers are suggested to improve the accuracy of NET detection, characterization, grading, staging, and predicting/monitoring NET responses to treatment including peptide receptor radionuclide therapy. The whole-body parametric Ki images generated from shortened dynamic PET using robust parametric imaging algorithm such as machine learning-based approach is potential for clinical and research in NET. In addition, dynamic PET can provide valuable information, such as biological distribution and radiation dose in tissue, in the study of new radioactive tracer in NET. It is expected that quantitative dynamic PET imaging in NET will be widely used for the imaging of somatostatin receptors and evaluation of therapeutic drugs and probes.

On Fluorophore Imaging by Diffusion Equation Model: Decompositions and Optimizations

Fluorescence imaging is a target-specific molecular imaging technology using absorption coefficient of fluorophore. For this imaging model governed by an inverse problem for the coupled diffusion system, which describes the interaction of the excitation field from several boundary sources and the corresponding emission field, we reformulate it as an optimization problem. For solving this non-quadratic optimizing problem, we propose a decomposition scheme, which extracts the horizontal information of the target from the boundary measurement data directly. The realizability of this hybrid imaging scheme is rigorously proved mathematically for cubic and ellipsoid targets, by constructing an indicator function for the horizontal location of the target explicitly. Then based on this horizonal location as a good initial guess for the iteration process, the cost functional is optimized efficiently using the trust domain scheme. Numerical implementations are provided to show the validity of the proposed scheme.

Biomarkers in ovarian cancer: To be or not to be

Biomarkers are becoming increasingly important in the treatment of epithelial ovarian cancer. Recent work from many laboratories has begun to provide clinically meaningful biomarkers. This review summarizes the state of the science regarding biomarkers for stratifying early-stage patients into those who benefit from adjuvant treatment, primary debulking versus interval debulking, and specific targeted therapy. In addition, new molecular imaging technologies have been developed to allow the surgeon to resect subvisible tumor deposits. These efforts should increase clinical effectiveness while minimizing toxicities for patients.

13C6,D8]2-deoxyglucose phosphorylation by hexokinase shows selectivity for the \u03b2-anomer

A non-radioactive 2-deoxyglucose (2DG) analog has been developed here for hyperpolarized magnetic resonance investigations. The analog, [13C6,D8]2DG, showed 13% polarization in solution (27,000-fold signal enhancement at the C1 site), following a dissolution-DNP hyperpolarization process. The phosphorylation of this analog by yeast hexokinase (yHK) was monitored in real-time with a temporal resolution of 1 s. We show that yHK selectively utilizes the β anomer of the 2DG analog, thus revealing a surprising anomeric specificity of this reaction. Such anomeric selectivity was not observed for the reaction of yHK or bacterial glucokinase with a hyperpolarized glucose analog. yHK is highly similar to the human HK-2, which is overexpressed in malignancy. Thus, the current finding may shed a new light on a fundamental enzyme activity which is utilized in the most widespread molecular imaging technology for cancer detection – positron-emission tomography with 18F-2DG.

Removal of random-valued impulse noise from Cerenkov luminescence images.

Cerenkov luminescence imaging(CLI) is an emerging molecular imaging technology able to optically visualize radioactive decay signals from medical isotopes and has found wide application in tumor diagnose, cancer therapy, drug development, intraoperative guidance, and so on. When Cerenkov luminescence data are collected, the high-energy particles from the radioactive nucleus will be detected by the sensitive CCD camera and lead to impulse noise. To suppress the impulse noise and improve the contrast of the useful signal to the background, the detection-based fuzzy switching median filtering framework is proposed in this paper. Several experiments were conducted respectively to investigate the statistical feature of the noise and to evaluate the performance of the proposed noise removal framework. The results show that the signal-to-noise ratio is improved after noise elimination. The proposed filtering framework outperforms the classical median filter in terms of root mean squared error and the structural similarity index. It also preserves the maximum value and the mean value in the regions of interest better than the median filter does. In addition, compared with the FLICMCDD algorithm, the proposed method works much faster while getting similar results. Graphical abstract.

Guidelines for application of computer-assisted indocyanine green molecular fluorescence imaging in diagnosis and surgical navigation of liver tumors (2019)

Computer-assisted combined indocyanine green (ICG) molecular fluorescence imaging technology can be used for preoperative planning and intraoperative detection from three-dimensional (3D) morphological anatomy and level of cellular function to guide the anatomical, functional and radical hepatectomy of liver tumor. This technology has received wide acceptance and has shown important diagnostic and therapeutic value. This guideline is intended to standardize the application of computer-assisted combined ICG molecular fluorescence imaging for accurate diagnosis and treatment of liver tumors in the following aspects: (1) the workflow of 3D visualization technology; (2) the mechanism and application flow of ICG molecular fluorescence imaging; (3) clinical application of 3D visualization technology and virtual reality technology; and (4) clinical application of ICG molecular fluorescence imaging. ICG molecular fluorescence imaging can help to define tumor boundary, determine hepatic segment and hepatic lobectomy tangent at the molecular and cellular level, and detect small lesions or metastases. According to the fluorescence signal characteristics of liver tumors and combined with rapid frozen pathological examination during operation, the differentiation degree of liver space-occupying lesions (such as primary liver cancer) can be preliminarily determined, and residual tumors and biliary leakage on the hepatic section can be detected after hepatectomy. Computer-assisted ICG molecular fluorescence imaging in the diagnosis and surgical navigation of liver tumors provides a new approach to digital diagnosis and treatment of liver tumors. With its development in clinical practice and the technological innovation, this technology will be further improved to allow more accurate diagnosis and treatment of liver tumors.

Localisation of PGK1 determines metabolic phenotype to balance metastasis and proliferation in patients with SMAD4-negative pancreatic cancer

ObjectivePancreatic ductal adenocarcinoma (PDAC) is the most aggressive type of GI tumour, and it possesses deregulated cellular energetics. Although recent advances in PDAC biology have led to the discovery of...

Precision surgery for cancer: a new surgical concept in individual tumor biology-based image-guided surgery

Surgery has long been a cornerstone of cancer treatment in many types of cancer. Traditionally, intraoperative assessment of the resection margin is largely dependent on visual inspection and palpation of tumors, with the aid of frozen section analysis. Although preoperative imaging can provide gross anatomical information, in situ translation of these images to the operation field is challenging. With the advancement of molecular imaging technology and its clinical application, the gap between preoperative radiologic images and surgical findings has been reduced through image-guided surgery. However, the imaging probes for intraoperative visualization of tumors are not individual tumor-specific. As conventional oncology has moved toward precision oncology with genomic and biological information specific to each tumor, image-guided surgery should also shift toward tumor biology-based image-guided surgery, so-called precision surgery for cancer. In precision cancer surgery, tumors should be analyzed molecularly and genetically to select the optimal imaging probes for individual tumors before surgical resection, beyond the use of predetermined imaging probes for certain types of cancer. This will raise the likelihood of meeting the surgical goals of cancer treatment. In summary, precision cancer surgery can be defined as individual tumor biology-based image-guided surgery. Keywords: Molecular imaging; Neoplasms; Precision oncology; Surgery; Surgery, computer-assisted

Advanced Nanotechnology Leading the Way to Multimodal Imaging-Guided Precision Surgical Therapy.

Surgical resection is the primary and most effective treatment for most patients with solid tumors. However, patients suffer from postoperative recurrence and metastasis. In the past years, emerging nanotechnology has led the way to minimally invasive, precision and intelligent oncological surgery after the rapid development of minimally invasive surgical technology. Advanced nanotechnology in the construction of nanomaterials (NMs) for precision imaging-guided surgery (IGS) as well as surgery-assisted synergistic therapy is summarized, thereby unlocking the advantages of nanotechnology in multimodal IGS-assisted precision synergistic cancer therapy. First, mechanisms and principles of NMs to surgical targets are briefly introduced. Multimodal imaging based on molecular imaging technologies provides a practical method to achieve intraoperative visualization with high resolution and deep tissue penetration. Moreover, multifunctional NMs synergize surgery with adjuvant therapy (e.g., chemotherapy, immunotherapy, phototherapy) to eliminate residual lesions. Finally, key issues in the development of ideal theranostic NMs associated with surgical applications and challenges of clinical transformation are discussed to push forward further development of NMs for multimodal IGS-assisted precision synergistic cancer therapy.

A Luciferase-fluorescent Reporter Influenza Virus for Live Imaging and Quantification of Viral Infection.

Influenza A viruses (IAVs) cause human respiratory disease that is associated with significant health and economic consequences. As with other viruses, studying IAV requires the use of laborious secondary approaches to detect the presence of the virus in infected cells and/or in animal models of infection. This limitation has been recently circumvented with the generation of recombinant IAVs expressing easily traceable fluorescent or bioluminescent (luciferase) reporter proteins. However, researchers have been forced to select fluorescent or luciferase reporter genes due to the restricted capacity of the IAV genome for including foreign sequences. To overcome this limitation, we have generated a recombinant replication-competent bi-reporter IAV (BIRFLU) stably expressing both a fluorescent and a luciferase reporter gene to easily track IAV infections in vitro and in vivo. To this end, the viral non-structural (NS) and hemagglutinin (HA) viral segments of influenza A/Puerto Rico/8/34 H1N1 (PR8) were modified to encode the fluorescent Venus and the bioluminescent Nanoluc luciferase proteins, respectively. Here, we describe the use of BIRFLU in a mouse model of IAV infection and the detection of both reporter genes using an in vivo imaging system. Notably, we have observed a good correlation between the expressions of both reporters and viral replication. The combination of cutting-edge techniques in molecular biology, animal research and imaging technologies, provides researchers the unique opportunity to use this tool for influenza research, including the study of virus-host interactions and dynamics of viral infections. Importantly, the feasibility to genetically alter the viral genome to express two foreign genes from different viral segments opens up opportunities to use this approach for: (i) the development of novel IAV vaccines, (ii) the generation of recombinant IAVs that can be used as vaccine vectors for the treatment of other human pathogen infections.

Acetone immersion enhanced MALDI-MS imaging of small molecule metabolites in biological tissues

Profiling the endogenous tissue metabolites with spatial features is significant for our understanding of molecular histology, and provides an insightful way to uncover the complex associations between tissue metabolic response and external stimuli. Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) is an effective molecular imaging technology to illustrate the spatial locations of molecules in tissue. However, due to the limited sensitivity and the presence of multiple matrix-related ions, it is still challenging to globally image the small molecule metabolites (SMMs) using MALDI, especially for those low-content functional ones. Here, a simple acetone washing method was developed to improve the sensitivity of MALDI-MS for imaging SMMs. After immersing in acetone and shaken for 15 min, key functional SMMs were well-visualized with significantly enhanced ion intensities. In addition to lipids, more than 160 SMM ions, including polyamines, cholines, carnitines, amino acids, nitrogenous bases, nucleosides, carbohydrates, organic acids, vitamins were imaged. The acetone washes-based MALDI-MSI was then applied to profile the metabolic alternations that occurred in osteosarcoma, and the abnormally altered SMMs and lipids were clearly visualized. Moreover, with the protection of acetone against tissue antigenicity, we successfully characterized the expression of three metabolites-related enzymes, fatty acid synthase (FASN), glutaminase (GLS), and cytosolic phospholipase A2 (cPLA2) in osteosarcoma. The spatially-resolved metabolite and corresponding enzyme information reveals what occured in osteosarcoma at the molecular level, providing new insights into the understanding of tumour metabolic reprogramming.

A recommended and verified procedure for in situ tryptic digestion of formalin-fixed paraffin-embedded tissues for analysis by matrix-assisted laser desorption/ionization imaging mass spectrometry.

Matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI IMS) is a molecular imaging technology uniquely capable of untargeted measurement of proteins, lipids, and metabolites while retaining spatial information about their location in situ. This powerful combination of capabilities has the potential to bring a wealth of knowledge to the field of molecular histology. Translation of this innovative research tool into clinical laboratories requires the development of reliable sample preparation protocols for the analysis of proteins from formalin-fixed paraffin-embedded (FFPE) tissues, the standard preservation process in clinical pathology. Although ideal for stained tissue analysis by microscopy, the FFPE process cross-links, disrupts, or can remove proteins from the tissue, making analysis of the protein content challenging. To date, reported approaches differ widely in process and efficacy. This tutorial presents a strategy derived from systematic testing and optimization of key parameters, for reproducible in situ tryptic digestion of proteins in FFPE tissue and subsequent MALDI IMS analysis. The approach describes a generalized method for FFPE tissues originating from virtually any source.

In vivo magnetic resonance imaging and spectroscopy. Technological advances and opportunities for applications continue to abound

Over the past decades, the field of in vivo magnetic resonance (MR) has built up an impressive repertoire of data acquisition and analysis technologies for anatomical, functional, physiological, and molecular imaging, the description of which requires many book volumes. As such it is impossible for a few authors to have an authoritative overview of the field and for a brief article to be inclusive. We will therefore focus mainly on data acquisition and attempt to give some insight into the principles underlying current advanced methods in the field and the potential for further innovation. In our view, the foreseeable future is expected to show continued rapid progress, for instance in imaging of microscopic tissue properties in vivo, assessment of functional and anatomical connectivity, higher resolution physiologic and metabolic imaging, and even imaging of receptor binding. In addition, acquisition speed and information content will continue to increase due to the continuous development of approaches for parallel imaging (including simultaneous multi-slice imaging), compressed sensing, and MRI fingerprinting. Finally, artificial intelligence approaches are becoming more realistic and will have a tremendous effect on both acquisition and analysis strategies. Together, these developments will continue to provide opportunity for scientific discovery and, in combination with large data sets from other fields such as genomics, allow the ultimate realization of precision medicine in the clinic.

Radiohalogenation of Organic Compounds: Practical Considerations and Challenges for Molecular Imaging

In the last few decades, advances in molecular imaging technologies have had a major impact on many aspects of healthcare. In particular, radiohalogenated compounds have been used for non-invasive visualization of human anatomy, for the diagnosis of disease and in drug development programs. As a consequence of these advances, a range of novel synthetic radiochemical methods have been reported that allow more effective and efficient radiohalogenation from a broader range of precursors. In developing new radiochemical methods, special requirements are required to optimize the incorporation of highly radioactive, short-lived, isotopically labelled reagents. This article highlights the key practical considerations and challenges encountered when utilizing the most commonly used radiohalogens in nuclear medicine.1 Introduction2 Synthetic Challenges for Radiohalogenation2.1 Radiofluorination2.2 Radioiodination3 Conclusions and Future Outlook

Application of multilayered strategy for variable selection in QSAR modeling of PET and SPECT imaging agents as diagnostic agents for Alzheimer’s disease

Non-invasive imaging of amyloid beta (Aβ) and tau fibrils in the brain may support an early and precise diagnosis of Alzheimer’s disease. Molecular imaging technologies involving radionuclides such as positron emission tomography (PET) and single-photon emission computed tomography (SPECT) against beta amyloid plaques and tau fibrils are among emerging research areas in the field of medicinal chemistry. In the current study, we have developed partial least square (PLS) regression-based two-dimensional quantitative structure-activity relationship (2D-QSAR) models using datasets of 38 PET and 73 SPECT imaging agents targeted against Aβ protein and 31 imaging agents (both PET and SPECT) targeted against tau protein. Following the strict Organization for Economic Co-operation and Development (OECD) guidelines, we have strived to select significant descriptors from the large initial pool of descriptors using multilayered variable selection strategy using the double cross-validation (DCV) method followed by the best subset selection (BSS) method prior to the development of the final PLS models. The developed models showed significant statistical performance and reliability. Molecular docking studies have been performed to understand the molecular interactions between the ligand and receptor, and the results are then correlated with the structural features obtained from the QSAR models. Furthermore, we have also designed some imaging agents based on the information provided by the models developed and some of them are predicted to be similar to or more active than the most active imaging agents present in the original dataset.

A Novel Fluorescent and Bioluminescent Bireporter Influenza A Virus To Evaluate Viral Infections.

Studying influenza A virus (IAV) requires the use of secondary approaches to detect the presence of virus in infected cells. To overcome this problem, we and others have generated recombinant IAV expressing fluorescent or luciferase reporter genes. These foreign reporter genes can be used as valid surrogates to track the presence of virus. However, the limited capacity for incorporating foreign sequences in the viral genome forced researchers to select a fluorescent or a luciferase reporter gene, depending on the type of study. To circumvent this limitation, we engineered a novel recombinant replication-competent bireporter IAV (BIRFLU) expressing both fluorescent and luciferase reporter genes. In cultured cells, BIRFLU displayed growth kinetics comparable to those of wild-type (WT) virus and was used to screen neutralizing antibodies or compounds with antiviral activity. The expression of two reporter genes allows monitoring of viral inhibition by fluorescence or bioluminescence, overcoming the limitations associated with the use of one reporter gene as a readout. In vivo, BIRFLU effectively infected mice, and both reporter genes were detected using in vivo imaging systems (IVIS). The ability to generate recombinant IAV harboring multiple foreign genes opens unique possibilities for studying virus-host interactions and for using IAV in high-throughput screenings (HTS) to identify novel antivirals that can be incorporated into the therapeutic armamentarium to control IAV infections. Moreover, the ability to genetically manipulate the viral genome to express two foreign genes offers the possibility of developing novel influenza vaccines and the feasibility for using recombinant IAV as vaccine vectors to treat other pathogen infections.IMPORTANCE Influenza A virus (IAV) causes a human respiratory disease that is associated with significant health and economic consequences. In recent years, the use of replication-competent IAV expressing an easily traceable fluorescent or luciferase reporter protein has significantly contributed to progress in influenza research. However, researchers have been forced to select a fluorescent or a luciferase reporter gene due to the restricted capacity of the influenza viral genome for including foreign sequences. To overcome this limitation, we generated, for the first time, a recombinant replication-competent bireporter IAV (BIRFLU) that stably expresses two reporter genes (one fluorescent and one luciferase) to track IAV infections in vitro and in vivo The combination of cutting-edge techniques from molecular biology, animal research, and imaging technologies brings researchers the unique opportunity to use this new generation of reporter-expressing IAV to study viral infection dynamics in both cultured cells and animal models of viral infection.

Ultrafast multi-slice chemical exchange saturation transfer imaging scheme based on segmented spatiotemporal encoding

Chemical exchange saturation transfer (CEST) imaging is an important magnetic resonance molecular imaging technology. However, long acquisition time limits its clinical application, especially when multi-slice CEST imaging is needed. Though single-shot EPI can be used to accelerate CEST imaging, images are often distorted under inhomogeneous magnetic fields. In this work, we propose a new method called CEST-SeSPEN for ultrafast multi-slice CEST imaging based on segmented spatiotemporally encoded (SeSPEN) MRI. Experiments were performed on creatine phantom and hen egg. The results show that CEST-SeSPEN can provide good CEST contrast images. Its acquisition time is much shorter than other multi-slice CEST methods currently available. It may be used in challenging situation where high temporal resolution and robustness to field inhomogeneity are vital.

In Vivo Translation of the CIRPI System: Revealing Molecular Pathology of Rabbit Aortic Atherosclerotic Plaques.

Thin-cap fibroatheroma (TCFA) are the unstable lesions in coronary artery disease that are prone to rupture, resulting in substantial morbidity and mortality worldwide. However, their small size and complex morphologic and biologic features make early detection and risk assessment difficult. We tested our newly developed catheter-based Circumferential-Intravascular-Radioluminescence-Photoacoustic-Imaging (CIRPI) system in vivo to enable detection and characterization of vulnerable plaque structure and biology in rabbit abdominal aorta. Methods: The CIRPI system includes a novel optical probe combining circumferential radioluminescence imaging and photoacoustic tomography (PAT). The probe's CaF2:Eu-based scintillating imaging window captures radioluminescence images (360° view) of plaques by detecting β-particles during 18F-FDG decay. A tunable laser-based PAT characterizes tissue constituents of plaque at 7 different wavelengths-540 and 560 nm (calcification), 920 nm (cholesteryl ester), 1040 nm (phospholipids), 1180 nm (elastin/collagen), 1210 nm (cholesterol), and 1235 nm (triglyceride). A single B-scan is concatenated from 330 A-lines captured during a 360° rotation. The abdominal aorta was imaged in vivo in both atherosclerotic rabbits (Watanabe Heritable Hyper Lipidemic [WHHL], 13-mo-old male, n = 5) and controls (New Zealand White, n = 2). Rabbits were fasted for 6 h before 5.55 × 107 Bq (1.5 mCi) of 18F-FDG were injected 1 h before the imaging procedure. Rabbits were anesthetized, and the right or left common carotid artery was surgically exposed. An 8 French catheter sheath was inserted into the common carotid artery, and a 0.035-cm (0.014-in) guidewire was advanced to the iliac artery, guided by x-ray fluoroscopy. A bare metal stent was implanted in the dorsal abdominal aorta as a landmark, followed by the 7 French imaging catheters that were advanced up to the proximal stent edge. Our CIRPI and clinical optical coherence tomography (OCT) were performed using pullback and nonocclusive flushing techniques. After imaging with the CIRPI system, the descending aorta was flushed with contrast agent, and OCT images were obtained with a pullback speed of 20 mm/s, providing images at 100 frames/s. Results were verified with histochemical analysis. Results: Our CIRPI system successfully detected the locations and characterized both stable and vulnerable aortic plaques in vivo among all WHHL rabbits. Calcification was detected from the stable plaque (540 and 560 nm), whereas TCFA exhibited phospholipids/cholesterol (1040 nm, 1210 nm). These findings were further verified with the clinical OCT system showing an area of low attenuation filled with lipids within TCFA. PAT images illustrated broken elastic fiber/collagen that could be verified with the histochemical analysis. All WHHL rabbits exhibited sparse to severe macrophages. Only 4 rabbits showed both moderate-to-severe level of calcifications and cholesterol clefts. However, all rabbits exhibited broken elastic fibers and collagen deposition. Control rabbits showed normal wall thickness with no presence of plaque tissue compositions. These findings were verified with OCT and histochemical analysis. Conclusion: Our novel multimodality hybrid system has been successfully translated to in vivo evaluation of atherosclerotic plaque structure and biology in a preclinical rabbit model. This system proposed a paradigm shift that unites molecular and pathologic imaging technologies. Therefore, the system may enhance the clinical evaluation of TCFA, as well as expand our understanding of coronary artery disease.