In vivo nanoparticle-mediated radiopharmaceutical-excited fluorescence molecular imaging

PubMed Central

Hu, Zhenhua; Qu, Yawei; Wang, Kun; Zhang, Xiaojun; Zha, Jiali; Song, Tianming; Bao, Chengpeng; Liu, Haixiao; Wang, Zhongliang; Wang, Jing; Liu, Zhongyu; Liu, Haifeng; Tian, Jie

2015-01-01

Cerenkov luminescence imaging utilizes visible photons emitted from radiopharmaceuticals to achieve in vivo optical molecular-derived signals. Since Cerenkov radiation is weak, non-optimum for tissue penetration and continuous regardless of biological interactions, it is challenging to detect this signal with a diagnostic dose. Therefore, it is challenging to achieve useful activated optical imaging for the acquisition of direct molecular information. Here we introduce a novel imaging strategy, which converts γ and Cerenkov radiation from radioisotopes into fluorescence through europium oxide nanoparticles. After a series of imaging studies, we demonstrate that this approach provides strong optical signals with high signal-to-background ratios, an ideal tissue penetration spectrum and activatable imaging ability. In comparison with present imaging techniques, it detects tumour lesions with low radioactive tracer uptake or small tumour lesions more effectively. We believe it will facilitate the development of nuclear and optical molecular imaging for new, highly sensitive imaging applications. PMID:26123615

Molecular-genetic imaging based on reporter gene expression.

PubMed

Kang, Joo Hyun; Chung, June-Key

2008-06-01

Molecular imaging includes proteomic, metabolic, cellular biologic process, and genetic imaging. In a narrow sense, molecular imaging means genetic imaging and can be called molecular-genetic imaging. Imaging reporter genes play a leading role in molecular-genetic imaging. There are 3 major methods of molecular-genetic imaging, based on optical, MRI, and nuclear medicine modalities. For each of these modalities, various reporter genes and probes have been developed, and these have resulted in successful transitions from bench to bedside applications. Each of these imaging modalities has its unique advantages and disadvantages. Fluorescent and bioluminescent optical imaging modalities are simple, less expensive, more convenient, and more user friendly than other imaging modalities. Another advantage, especially of bioluminescence imaging, is its ability to detect low levels of gene expression. MRI has the advantage of high spatial resolution, whereas nuclear medicine methods are highly sensitive and allow data from small-animal imaging studies to be translated to clinical practice. Moreover, multimodality imaging reporter genes will allow us to choose the imaging technologies that are most appropriate for the biologic problem at hand and facilitate the clinical application of reporter gene technologies. Reporter genes can be used to visualize the levels of expression of particular exogenous and endogenous genes and several intracellular biologic phenomena, including specific signal transduction pathways, nuclear receptor activities, and protein-protein interactions. This technique provides a straightforward means of monitoring tumor mass and can visualize the in vivo distributions of target cells, such as immune cells and stem cells. Molecular imaging has gradually evolved into an important tool for drug discovery and development, and transgenic mice with an imaging reporter gene can be useful during drug and stem cell therapy development. Moreover, instrumentation improvements, the identification of novel targets and genes, and imaging probe developments suggest that molecular-genetic imaging is likely to play an increasingly important role in the diagnosis and therapy of cancer.

A DICOM-based 2nd generation Molecular Imaging Data Grid implementing the IHE XDS-i integration profile.

PubMed

Lee, Jasper; Zhang, Jianguo; Park, Ryan; Dagliyan, Grant; Liu, Brent; Huang, H K

2012-07-01

A Molecular Imaging Data Grid (MIDG) was developed to address current informatics challenges in archival, sharing, search, and distribution of preclinical imaging studies between animal imaging facilities and investigator sites. This manuscript presents a 2nd generation MIDG replacing the Globus Toolkit with a new system architecture that implements the IHE XDS-i integration profile. Implementation and evaluation were conducted using a 3-site interdisciplinary test-bed at the University of Southern California. The 2nd generation MIDG design architecture replaces the initial design's Globus Toolkit with dedicated web services and XML-based messaging for dedicated management and delivery of multi-modality DICOM imaging datasets. The Cross-enterprise Document Sharing for Imaging (XDS-i) integration profile from the field of enterprise radiology informatics was adopted into the MIDG design because streamlined image registration, management, and distribution dataflow are likewise needed in preclinical imaging informatics systems as in enterprise PACS application. Implementation of the MIDG is demonstrated at the University of Southern California Molecular Imaging Center (MIC) and two other sites with specified hardware, software, and network bandwidth. Evaluation of the MIDG involves data upload, download, and fault-tolerance testing scenarios using multi-modality animal imaging datasets collected at the USC Molecular Imaging Center. The upload, download, and fault-tolerance tests of the MIDG were performed multiple times using 12 collected animal study datasets. Upload and download times demonstrated reproducibility and improved real-world performance. Fault-tolerance tests showed that automated failover between Grid Node Servers has minimal impact on normal download times. Building upon the 1st generation concepts and experiences, the 2nd generation MIDG system improves accessibility of disparate animal-model molecular imaging datasets to users outside a molecular imaging facility's LAN using a new architecture, dataflow, and dedicated DICOM-based management web services. Productivity and efficiency of preclinical research for translational sciences investigators has been further streamlined for multi-center study data registration, management, and distribution.

First-in-Human Ultrasound Molecular Imaging With a VEGFR2-Specific Ultrasound Molecular Contrast Agent (BR55) in Prostate Cancer: A Safety and Feasibility Pilot Study.

PubMed

Smeenge, Martijn; Tranquart, François; Mannaerts, Christophe K; de Reijke, Theo M; van de Vijver, Marc J; Laguna, M Pilar; Pochon, Sibylle; de la Rosette, Jean J M C H; Wijkstra, Hessel

2017-07-01

BR55, a vascular endothelial growth factor receptor 2 (VEGFR2)-specific ultrasound molecular contrast agent (MCA), has shown promising results in multiple preclinical models regarding cancer imaging. In this first-in-human, phase 0, exploratory study, we investigated the feasibility and safety of the MCA for the detection of prostate cancer (PCa) in men using clinical standard technology. Imaging with the MCA was performed in 24 patients with biopsy-proven PCa scheduled for radical prostatectomy using a clinical ultrasound scanner at low acoustic power. Safety monitoring was done by physical examination, blood pressure and heart rate measurements, electrocardiogram, and blood sampling. As first-in-human study, MCA dosing and imaging protocol were necessarily fine-tuned along the enrollment to improve visualization. Imaging data were correlated with radical prostatectomy histopathology to analyze the detection rate of ultrasound molecular imaging with the MCA. Imaging with MCA doses of 0.03 and 0.05 mL/kg was adequate to obtain contrast enhancement images up to 30 minutes after administration. No serious adverse events or clinically meaningful changes in safety monitoring data were identified during or after administration. BR55 dosing and imaging were fine-tuned in the first 12 patients leading to 12 subsequent patients with an improved MCA dosing and imaging protocol. Twenty-three patients underwent radical prostatectomy. A total of 52 lesions were determined to be malignant by histopathology with 26 (50%) of them seen during BR55 imaging. In the 11 patients that were scanned with the improved protocol and underwent radical prostatectomy, a total of 28 malignant lesions were determined: 19 (68%) were seen during BR55 ultrasound molecular imaging, whereas 9 (32%) were not identified. Ultrasound molecular imaging with BR55 is feasible with clinical standard technology and demonstrated a good safety profile. Detectable levels of the MCA can be reached in patients with PCa opening the way for further clinical trials.

Natural language processing and visualization in the molecular imaging domain.

PubMed

Tulipano, P Karina; Tao, Ying; Millar, William S; Zanzonico, Pat; Kolbert, Katherine; Xu, Hua; Yu, Hong; Chen, Lifeng; Lussier, Yves A; Friedman, Carol

2007-06-01

Molecular imaging is at the crossroads of genomic sciences and medical imaging. Information within the molecular imaging literature could be used to link to genomic and imaging information resources and to organize and index images in a way that is potentially useful to researchers. A number of natural language processing (NLP) systems are available to automatically extract information from genomic literature. One existing NLP system, known as BioMedLEE, automatically extracts biological information consisting of biomolecular substances and phenotypic data. This paper focuses on the adaptation, evaluation, and application of BioMedLEE to the molecular imaging domain. In order to adapt BioMedLEE for this domain, we extend an existing molecular imaging terminology and incorporate it into BioMedLEE. BioMedLEE's performance is assessed with a formal evaluation study. The system's performance, measured as recall and precision, is 0.74 (95% CI: [.70-.76]) and 0.70 (95% CI [.63-.76]), respectively. We adapt a JAVA viewer known as PGviewer for the simultaneous visualization of images with NLP extracted information.

MIDG-Emerging grid technologies for multi-site preclinical molecular imaging research communities.

PubMed

Lee, Jasper; Documet, Jorge; Liu, Brent; Park, Ryan; Tank, Archana; Huang, H K

2011-03-01

Molecular imaging is the visualization and identification of specific molecules in anatomy for insight into metabolic pathways, tissue consistency, and tracing of solute transport mechanisms. This paper presents the Molecular Imaging Data Grid (MIDG) which utilizes emerging grid technologies in preclinical molecular imaging to facilitate data sharing and discovery between preclinical molecular imaging facilities and their collaborating investigator institutions to expedite translational sciences research. Grid-enabled archiving, management, and distribution of animal-model imaging datasets help preclinical investigators to monitor, access and share their imaging data remotely, and promote preclinical imaging facilities to share published imaging datasets as resources for new investigators. The system architecture of the Molecular Imaging Data Grid is described in a four layer diagram. A data model for preclinical molecular imaging datasets is also presented based on imaging modalities currently used in a molecular imaging center. The MIDG system components and connectivity are presented. And finally, the workflow steps for grid-based archiving, management, and retrieval of preclincial molecular imaging data are described. Initial performance tests of the Molecular Imaging Data Grid system have been conducted at the USC IPILab using dedicated VMware servers. System connectivity, evaluated datasets, and preliminary results are presented. The results show the system's feasibility, limitations, direction of future research. Translational and interdisciplinary research in medicine is increasingly interested in cellular and molecular biology activity at the preclinical levels, utilizing molecular imaging methods on animal models. The task of integrated archiving, management, and distribution of these preclinical molecular imaging datasets at preclinical molecular imaging facilities is challenging due to disparate imaging systems and multiple off-site investigators. A Molecular Imaging Data Grid design, implementation, and initial evaluation is presented to demonstrate the secure and novel data grid solution for sharing preclinical molecular imaging data across the wide-area-network (WAN).

Dual Contrast - Magnetic Resonance Fingerprinting (DC-MRF): A Platform for Simultaneous Quantification of Multiple MRI Contrast Agents.

PubMed

Anderson, Christian E; Donnola, Shannon B; Jiang, Yun; Batesole, Joshua; Darrah, Rebecca; Drumm, Mitchell L; Brady-Kalnay, Susann M; Steinmetz, Nicole F; Yu, Xin; Griswold, Mark A; Flask, Chris A

2017-08-16

Injectable Magnetic Resonance Imaging (MRI) contrast agents have been widely used to provide critical assessments of disease for both clinical and basic science imaging research studies. The scope of available MRI contrast agents has expanded over the years with the emergence of molecular imaging contrast agents specifically targeted to biological markers. Unfortunately, synergistic application of more than a single molecular contrast agent has been limited by MRI's ability to only dynamically measure a single agent at a time. In this study, a new Dual Contrast - Magnetic Resonance Fingerprinting (DC - MRF) methodology is described that can detect and independently quantify the local concentration of multiple MRI contrast agents following simultaneous administration. This "multi-color" MRI methodology provides the opportunity to monitor multiple molecular species simultaneously and provides a practical, quantitative imaging framework for the eventual clinical translation of molecular imaging contrast agents.

Homing peptide guiding optical molecular imaging for the diagnosis of bladder cancer

NASA Astrophysics Data System (ADS)

Yang, Xiao-feng; Pang, Jian-zhi; Liu, Jie-hao; Zhao, Yang; Jia, Xing-you; Li, Jun; Liu, Reng-xin; Wang, Wei; Fan, Zhen-wei; Zhang, Zi-qiang; Yan, San-hua; Luo, Jun-qian; Zhang, Xiao-lei

2014-11-01

Background: The limitations of primary transurethral resection of bladder tumor (TURBt) have led the residual tumors rates as high as 75%. The intraoperative fluorescence imaging offers a great potential for improving TURBt have been confirmed. So we aim to distinguish the residual tumors and normal mucosa using fluorescence molecular imaging formed by conjugated molecule of the CSNRDARRC bladder cancer homing peptide with fluorescent dye. The conjugated molecule was abbreviated FIuo-ACP. In our study, we will research the image features of FIuo-ACP probe targeted bladder cancer for fluorescence molecular imaging diagnosis for bladder cancer in vivo and ex vivo. Methods: After the FIuo-ACP probe was synthetized, the binding sites, factors affecting binding rates, the specificity and the targeting of Fluo-ACP labeled with bladder cancer cells were studied respectively by laser scanning confocal microscope (LSCM), immunofluorescence and multispectral fluorescence ex vivo optical molecular imaging system. Results: The binding sites were located in nucleus and the binding rates were correlated linearly with the dose of probe and the grade of pathology. Moreover, the probe has a binding specificity with bladder cancer in vivo and ex vivo. Tumor cells being labeled by the Fluo-ACP, bright green spots were observed under LSCM. The tissue samples and tumor cells can be labeled and identified by fluorescence microscope. Optical molecular imaging of xenograft tumor tissues was exhibited as fluorescent spots under EMCCD. Conclusion: The CSNRDARRC peptides might be a useful bladder cancer targeting vector. The FIuo-ACP molecular probe was suitable for fluorescence molecular imaging diagnosis for bladder cancer in vivo and ex vivo.

Potential of PET-MRI for imaging of non-oncologic musculoskeletal disease.

PubMed

Kogan, Feliks; Fan, Audrey P; Gold, Garry E

2016-12-01

Early detection of musculoskeletal disease leads to improved therapies and patient outcomes, and would benefit greatly from imaging at the cellular and molecular level. As it becomes clear that assessment of multiple tissues and functional processes are often necessary to study the complex pathogenesis of musculoskeletal disorders, the role of multi-modality molecular imaging becomes increasingly important. New positron emission tomography-magnetic resonance imaging (PET-MRI) systems offer to combine high-resolution MRI with simultaneous molecular information from PET to study the multifaceted processes involved in numerous musculoskeletal disorders. In this article, we aim to outline the potential clinical utility of hybrid PET-MRI to these non-oncologic musculoskeletal diseases. We summarize current applications of PET molecular imaging in osteoarthritis (OA), rheumatoid arthritis (RA), metabolic bone diseases and neuropathic peripheral pain. Advanced MRI approaches that reveal biochemical and functional information offer complementary assessment in soft tissues. Additionally, we discuss technical considerations for hybrid PET-MR imaging including MR attenuation correction, workflow, radiation dose, and quantification.

Molecular Imaging of Human Embryonic Stem Cells Stably Expressing Human PET Reporter Genes After Zinc Finger Nuclease-Mediated Genome Editing.

PubMed

Wolfs, Esther; Holvoet, Bryan; Ordovas, Laura; Breuls, Natacha; Helsen, Nicky; Schönberger, Matthias; Raitano, Susanna; Struys, Tom; Vanbilloen, Bert; Casteels, Cindy; Sampaolesi, Maurilio; Van Laere, Koen; Lambrichts, Ivo; Verfaillie, Catherine M; Deroose, Christophe M

2017-10-01

Molecular imaging is indispensable for determining the fate and persistence of engrafted stem cells. Standard strategies for transgene induction involve the use of viral vectors prone to silencing and insertional mutagenesis or the use of nonhuman genes. Methods: We used zinc finger nucleases to induce stable expression of human imaging reporter genes into the safe-harbor locus adeno-associated virus integration site 1 in human embryonic stem cells. Plasmids were generated carrying reporter genes for fluorescence, bioluminescence imaging, and human PET reporter genes. Results: In vitro assays confirmed their functionality, and embryonic stem cells retained differentiation capacity. Teratoma formation assays were performed, and tumors were imaged over time with PET and bioluminescence imaging. Conclusion: This study demonstrates the application of genome editing for targeted integration of human imaging reporter genes in human embryonic stem cells for long-term molecular imaging. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

Nonlinear Interferometric Vibrational Imaging (NIVI) with Novel Optical Sources

NASA Astrophysics Data System (ADS)

Boppart, Stephen A.; King, Matthew D.; Liu, Yuan; Tu, Haohua; Gruebele, Martin

Optical imaging is essential in medicine and in fundamental studies of biological systems. Although many existing imaging modalities can supply valuable information, not all are capable of label-free imaging with high-contrast and molecular specificity. The application of molecular or nanoparticle contrast agents may adversely influence the biological system under investigation. These substances also present ongoing concerns over toxicity or particle clearance, which must be properly addressed before their approval for in vivo human imaging. Hence there is an increasing appreciation for label-free imaging techniques. It is of primary importance to develop imaging techniques that can indiscriminately identify and quantify biochemical compositions to high degrees of sensitivity and specificity through only the intrinsic optical response of endogenous molecular species. The development and use of nonlinear interferometric vibrational imaging, which is based on the interferometric detection of optical signals from coherent anti-Stokes Raman scattering (CARS), along with novel optical sources, offers the potential for label-free molecular imaging.

Molecular imaging of Alzheimer disease pathology.

PubMed

Kantarci, K

2014-06-01

Development of molecular imaging agents for fibrillar β-amyloid positron-emission tomography during the past decade has brought molecular imaging of Alzheimer disease pathology into the spotlight. Large cohort studies with longitudinal follow-up in cognitively normal individuals and patients with mild cognitive impairment and Alzheimer disease indicate that β-amyloid deposition can be detected many years before the onset of symptoms with molecular imaging, and its progression can be followed longitudinally. The utility of β-amyloid PET in the differential diagnosis of Alzheimer disease is greatest when there is no pathologic overlap between 2 dementia syndromes, such as in frontotemporal lobar degeneration and Alzheimer disease. However β-amyloid PET alone may be insufficient in distinguishing dementia syndromes that commonly have overlapping β-amyloid pathology, such as dementia with Lewy bodies and vascular dementia, which represent the 2 most common dementia pathologies after Alzheimer disease. The role of molecular imaging in Alzheimer disease clinical trials is growing rapidly, especially in an era when preventive interventions are designed to eradicate the pathology targeted by molecular imaging agents. © 2014 by American Journal of Neuroradiology.

Molecular Imaging: Current Status and Emerging Strategies

PubMed Central

Pysz, Marybeth A.; Gambhir, Sanjiv S.; Willmann, Jürgen K.

2011-01-01

In vivo molecular imaging has a great potential to impact medicine by detecting diseases in early stages (screening), identifying extent of disease, selecting disease- and patient-specific therapeutic treatment (personalized medicine), applying a directed or targeted therapy, and measuring molecular-specific effects of treatment. Current clinical molecular imaging approaches primarily use PET- or SPECT-based techniques. In ongoing preclinical research novel molecular targets of different diseases are identified and, sophisticated and multifunctional contrast agents for imaging these molecular targets are developed along with new technologies and instrumentation for multimodality molecular imaging. Contrast-enhanced molecular ultrasound with molecularly-targeted contrast microbubbles is explored as a clinically translatable molecular imaging strategy for screening, diagnosing, and monitoring diseases at the molecular level. Optical imaging with fluorescent molecular probes and ultrasound imaging with molecularly-targeted microbubbles are attractive strategies since they provide real-time imaging, are relatively inexpensive, produce images with high spatial resolution, and do not involve exposure to ionizing irradiation. Raman spectroscopy/microscopy has emerged as a molecular optical imaging strategy for ultrasensitive detection of multiple biomolecules/biochemicals with both in vivo and ex vivo versatility. Photoacoustic imaging is a hybrid of optical and ultrasound modalities involving optically-excitable molecularly-targeted contrast agents and quantitative detection of resulting oscillatory contrast agent movement with ultrasound. Current preclinical findings and advances in instrumentation such as endoscopes and microcatheters suggest that these molecular imaging modalities have numerous clinical applications and will be translated into clinical use in the near future. PMID:20541650

Quantitative imaging as cancer biomarker

NASA Astrophysics Data System (ADS)

Mankoff, David A.

2015-03-01

The ability to assay tumor biologic features and the impact of drugs on tumor biology is fundamental to drug development. Advances in our ability to measure genomics, gene expression, protein expression, and cellular biology have led to a host of new targets for anticancer drug therapy. In translating new drugs into clinical trials and clinical practice, these same assays serve to identify patients most likely to benefit from specific anticancer treatments. As cancer therapy becomes more individualized and targeted, there is an increasing need to characterize tumors and identify therapeutic targets to select therapy most likely to be successful in treating the individual patient's cancer. Thus far assays to identify cancer therapeutic targets or anticancer drug pharmacodynamics have been based upon in vitro assay of tissue or blood samples. Advances in molecular imaging, particularly PET, have led to the ability to perform quantitative non-invasive molecular assays. Imaging has traditionally relied on structural and anatomic features to detect cancer and determine its extent. More recently, imaging has expanded to include the ability to image regional biochemistry and molecular biology, often termed molecular imaging. Molecular imaging can be considered an in vivo assay technique, capable of measuring regional tumor biology without perturbing it. This makes molecular imaging a unique tool for cancer drug development, complementary to traditional assay methods, and a potentially powerful method for guiding targeted therapy in clinical trials and clinical practice. The ability to quantify, in absolute measures, regional in vivo biologic parameters strongly supports the use of molecular imaging as a tool to guide therapy. This review summarizes current and future applications of quantitative molecular imaging as a biomarker for cancer therapy, including the use of imaging to (1) identify patients whose tumors express a specific therapeutic target; (2) determine whether the drug reaches the target; (3) identify an early response to treatment; and (4) predict the impact of therapy on long-term outcomes such as survival. The manuscript reviews basic concepts important in the application of molecular imaging to cancer drug therapy, in general, and will discuss specific examples of studies in humans, and highlight future directions, including ongoing multi-center clinical trials using molecular imaging as a cancer biomarker.

Probing the brain with molecular fMRI.

PubMed

Ghosh, Souparno; Harvey, Peter; Simon, Jacob C; Jasanoff, Alan

2018-06-01

One of the greatest challenges of modern neuroscience is to incorporate our growing knowledge of molecular and cellular-scale physiology into integrated, organismic-scale models of brain function in behavior and cognition. Molecular-level functional magnetic resonance imaging (molecular fMRI) is a new technology that can help bridge these scales by mapping defined microscopic phenomena over large, optically inaccessible regions of the living brain. In this review, we explain how MRI-detectable imaging probes can be used to sensitize noninvasive imaging to mechanistically significant components of neural processing. We discuss how a combination of innovative probe design, advanced imaging methods, and strategies for brain delivery can make molecular fMRI an increasingly successful approach for spatiotemporally resolved studies of diverse neural phenomena, perhaps eventually in people. Copyright © 2018 Elsevier Ltd. All rights reserved.

Advanced imaging techniques for the study of plant growth and development.

PubMed

Sozzani, Rosangela; Busch, Wolfgang; Spalding, Edgar P; Benfey, Philip N

2014-05-01

A variety of imaging methodologies are being used to collect data for quantitative studies of plant growth and development from living plants. Multi-level data, from macroscopic to molecular, and from weeks to seconds, can be acquired. Furthermore, advances in parallelized and automated image acquisition enable the throughput to capture images from large populations of plants under specific growth conditions. Image-processing capabilities allow for 3D or 4D reconstruction of image data and automated quantification of biological features. These advances facilitate the integration of imaging data with genome-wide molecular data to enable systems-level modeling. Copyright © 2013 Elsevier Ltd. All rights reserved.

Current applications of molecular imaging and luminescence-based techniques in traditional Chinese medicine.

PubMed

Li, Jinhui; Wan, Haitong; Zhang, Hong; Tian, Mei

2011-09-01

Traditional Chinese medicine (TCM), which is fundamentally different from Western medicine, has been widely investigated using various approaches. Cellular- or molecular-based imaging has been used to investigate and illuminate the various challenges identified and progress made using therapeutic methods in TCM. Insight into the processes of TCM at the cellular and molecular changes and the ability to image these processes will enhance our understanding of various diseases of TCM and will provide new tools to diagnose and treat patients. Various TCM therapies including herbs and formulations, acupuncture and moxibustion, massage, Gua Sha, and diet therapy have been analyzed using positron emission tomography, single photon emission computed tomography, functional magnetic resonance imaging and ultrasound and optical imaging. These imaging tools have kept pace with developments in molecular biology, nuclear medicine, and computer technology. We provide an overview of recent developments in demystifying ancient knowledge - like the power of energy flow and blood flow meridians, and serial naturopathies - which are essential to visually and vividly recognize the body using modern technology. In TCM, treatment can be individualized in a holistic or systematic view that is consistent with molecular imaging technologies. Future studies might include using molecular imaging in conjunction with TCM to easily diagnose or monitor patients naturally and noninvasively. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Oral Administration and Detection of a Near-Infrared Molecular Imaging Agent in an Orthotopic Mouse Model for Breast Cancer Screening

PubMed Central

2018-01-01

Molecular imaging is advantageous for screening diseases such as breast cancer by providing precise spatial information on disease-associated biomarkers, something neither blood tests nor anatomical imaging can achieve. However, the high cost and risks of ionizing radiation for several molecular imaging modalities have prevented a feasible and scalable approach for screening. Clinical studies have demonstrated the ability to detect breast tumors using nonspecific probes such as indocyanine green, but the lack of molecular information and required intravenous contrast agent does not provide a significant benefit over current noninvasive imaging techniques. Here we demonstrate that negatively charged sulfate groups, commonly used to improve solubility of near-infrared fluorophores, enable sufficient oral absorption and targeting of fluorescent molecular imaging agents for completely noninvasive detection of diseased tissue such as breast cancer. These functional groups improve the pharmacokinetic properties of affinity ligands to achieve targeting efficiencies compatible with clinical imaging devices using safe, nonionizing radiation (near-infrared light). Together, this enables development of a “disease screening pill” capable of oral absorption and systemic availability, target binding, background clearance, and imaging at clinically relevant depths for breast cancer screening. This approach should be adaptable to other molecular targets and diseases for use as a new class of screening agents. PMID:29696981

Oral Administration and Detection of a Near-Infrared Molecular Imaging Agent in an Orthotopic Mouse Model for Breast Cancer Screening.

PubMed

Bhatnagar, Sumit; Verma, Kirti Dhingra; Hu, Yongjun; Khera, Eshita; Priluck, Aaron; Smith, David E; Thurber, Greg M

2018-05-07

Molecular imaging is advantageous for screening diseases such as breast cancer by providing precise spatial information on disease-associated biomarkers, something neither blood tests nor anatomical imaging can achieve. However, the high cost and risks of ionizing radiation for several molecular imaging modalities have prevented a feasible and scalable approach for screening. Clinical studies have demonstrated the ability to detect breast tumors using nonspecific probes such as indocyanine green, but the lack of molecular information and required intravenous contrast agent does not provide a significant benefit over current noninvasive imaging techniques. Here we demonstrate that negatively charged sulfate groups, commonly used to improve solubility of near-infrared fluorophores, enable sufficient oral absorption and targeting of fluorescent molecular imaging agents for completely noninvasive detection of diseased tissue such as breast cancer. These functional groups improve the pharmacokinetic properties of affinity ligands to achieve targeting efficiencies compatible with clinical imaging devices using safe, nonionizing radiation (near-infrared light). Together, this enables development of a "disease screening pill" capable of oral absorption and systemic availability, target binding, background clearance, and imaging at clinically relevant depths for breast cancer screening. This approach should be adaptable to other molecular targets and diseases for use as a new class of screening agents.

High sensitivity optical molecular imaging system

NASA Astrophysics Data System (ADS)

An, Yu; Yuan, Gao; Huang, Chao; Jiang, Shixin; Zhang, Peng; Wang, Kun; Tian, Jie

2018-02-01

Optical Molecular Imaging (OMI) has the advantages of high sensitivity, low cost and ease of use. By labeling the regions of interest with fluorescent or bioluminescence probes, OMI can noninvasively obtain the distribution of the probes in vivo, which play the key role in cancer research, pharmacokinetics and other biological studies. In preclinical and clinical application, the image depth, resolution and sensitivity are the key factors for researchers to use OMI. In this paper, we report a high sensitivity optical molecular imaging system developed by our group, which can improve the imaging depth in phantom to nearly 5cm, high resolution at 2cm depth, and high image sensitivity. To validate the performance of the system, special designed phantom experiments and weak light detection experiment were implemented. The results shows that cooperated with high performance electron-multiplying charge coupled device (EMCCD) camera, precision design of light path system and high efficient image techniques, our OMI system can simultaneously collect the light-emitted signals generated by fluorescence molecular imaging, bioluminescence imaging, Cherenkov luminance and other optical imaging modality, and observe the internal distribution of light-emitting agents fast and accurately.

Imaging mass spectrometry in drug development and toxicology.

PubMed

Karlsson, Oskar; Hanrieder, Jörg

2017-06-01

During the last decades, imaging mass spectrometry has gained significant relevance in biomedical research. Recent advances in imaging mass spectrometry have paved the way for in situ studies on drug development, metabolism and toxicology. In contrast to whole-body autoradiography that images the localization of radiolabeled compounds, imaging mass spectrometry provides the possibility to simultaneously determine the discrete tissue distribution of the parent compound and its metabolites. In addition, imaging mass spectrometry features high molecular specificity and allows comprehensive, multiplexed detection and localization of hundreds of proteins, peptides and lipids directly in tissues. Toxicologists traditionally screen for adverse findings by histopathological examination. However, studies of the molecular and cellular processes underpinning toxicological and pathologic findings induced by candidate drugs or toxins are important to reach a mechanistic understanding and an effective risk assessment strategy. One of IMS strengths is the ability to directly overlay the molecular information from the mass spectrometric analysis with the tissue section and allow correlative comparisons of molecular and histologic information. Imaging mass spectrometry could therefore be a powerful tool for omics profiling of pharmacological/toxicological effects of drug candidates and toxicants in discrete tissue regions. The aim of the present review is to provide an overview of imaging mass spectrometry, with particular focus on MALDI imaging mass spectrometry, and its use in drug development and toxicology in general.

In Vivo Investigation of Breast Cancer Progression by Use of an Internal Control1

PubMed Central

Baeten, John; Haller, Jodi; Shih, Helen; Ntziachristos, Vasilis

2009-01-01

Optical imaging of breast cancer has been considered for detecting functional and molecular characteristics of diseases in clinical and preclinical settings. Applied to laboratory research, photonic investigations offer a highly versatile tool for preclinical imaging and drug discovery. A particular advantage of the optical method is the availability of multiple spectral bands for performing imaging. Herein, we capitalize on this feature to demonstrate how it is possible to use different wavelengths to offer internal controls and significantly improve the observation accuracy in molecular imaging applications. In particular, we show the independent in vivo detection of cysteine proteases along with tumor permeability and interstitial volume measurements using a dual-wavelength approach. To generate results with a view toward clinically geared studies, a transgenic Her2/neu mouse model that spontaneously developed mammary tumors was used. In vivo findings were validated against conventional ex vivo tests such as histology and Western blot analyses. By correcting for biodistribution parameters, the dual-wavelength method increases the accuracy of molecular observations by separating true molecular target from probe biodistribution. As such, the method is highly appropriate for molecular imaging studies where often probe delivery and target presence are not independently assessed. On the basis of these findings, we propose the dual-wavelength/normalization approach as an essential method for drug discovery and preclinical imaging studies. PMID:19242603

Harnessing Integrative Omics to Facilitate Molecular Imaging of the Human Epidermal Growth Factor Receptor Family for Precision Medicine.

PubMed

Pool, Martin; de Boer, H Rudolf; Hooge, Marjolijn N Lub-de; van Vugt, Marcel A T M; de Vries, Elisabeth G E

2017-01-01

Cancer is a growing problem worldwide. The cause of death in cancer patients is often due to treatment-resistant metastatic disease. Many molecularly targeted anticancer drugs have been developed against 'oncogenic driver' pathways. However, these treatments are usually only effective in properly selected patients. Resistance to molecularly targeted drugs through selective pressure on acquired mutations or molecular rewiring can hinder their effectiveness. This review summarizes how molecular imaging techniques can potentially facilitate the optimal implementation of targeted agents. Using the human epidermal growth factor receptor (HER) family as a model in (pre)clinical studies, we illustrate how molecular imaging may be employed to characterize whole body target expression as well as monitor drug effectiveness and the emergence of tumor resistance. We further discuss how an integrative omics discovery platform could guide the selection of 'effect sensors' - new molecular imaging targets - which are dynamic markers that indicate treatment effectiveness or resistance.

Institute for Molecular Medicine Research Program

DOE Office of Scientific and Technical Information (OSTI.GOV)

Phelps, Michael E

2012-12-14

The objectives of the project are the development of new Positron Emission Tomography (PET) imaging instrumentation, chemistry technology platforms and new molecular imaging probes to examine the transformations from normal cellular and biological processes to those of disease in pre-clinical animal models. These technology platforms and imaging probes provide the means to: 1. Study the biology of disease using pre-clinical mouse models and cells. 2. Develop molecular imaging probes for imaging assays of proteins in pre-clinical models. 3. Develop imaging assays in pre-clinical models to provide to other scientists the means to guide and improve the processes for discovering newmore » drugs. 4. Develop imaging assays in pre-clinical models for others to use in judging the impact of drugs on the biology of disease.« less

Advantages in functional imaging of the brain.

PubMed

Mier, Walter; Mier, Daniela

2015-01-01

As neuronal pathologies cause only minor morphological alterations, molecular imaging techniques are a prerequisite for the study of diseases of the brain. The development of molecular probes that specifically bind biochemical markers and the advances of instrumentation have revolutionized the possibilities to gain insight into the human brain organization and beyond this-visualize structure-function and brain-behavior relationships. The review describes the development and current applications of functional brain imaging techniques with a focus on applications in psychiatry. A historical overview of the development of functional imaging is followed by the portrayal of the principles and applications of positron emission tomography (PET) and functional magnetic resonance imaging (fMRI), two key molecular imaging techniques that have revolutionized the ability to image molecular processes in the brain. We conclude that the juxtaposition of PET and fMRI in hybrid PET/MRI scanners enhances the significance of both modalities for research in neurology and psychiatry and might pave the way for a new area of personalized medicine.

Molecular imaging of inflammation and intraplaque vasa vasorum: A step forward to identification of vulnerable plaques?

PubMed Central

ten Kate, Gerrit L.; Sijbrands, Eric J. G.; Valkema, Roelf; ten Cate, Folkert J.; Feinstein, Steven B.; van der Steen, Antonius F. W.; Daemen, Mat J. A. P.

2010-01-01

Current developments in cardiovascular biology and imaging enable the noninvasive molecular evaluation of atherosclerotic vascular disease. Intraplaque neovascularization sprouting from the adventitial vasa vasorum has been identified as an independent predictor of intraplaque hemorrhage and plaque rupture. These intraplaque vasa vasorum result from angiogenesis, most likely under influence of hypoxic and inflammatory stimuli. Several molecular imaging techniques are currently available. Most experience has been obtained with molecular imaging using positron emission tomography and single photon emission computed tomography. Recently, the development of targeted contrast agents has allowed molecular imaging with magnetic resonance imaging, ultrasound and computed tomography. The present review discusses the use of these molecular imaging techniques to identify inflammation and intraplaque vasa vasorum to identify vulnerable atherosclerotic plaques at risk of rupture and thrombosis. The available literature on molecular imaging techniques and molecular targets associated with inflammation and angiogenesis is discussed, and the clinical applications of molecular cardiovascular imaging and the use of molecular techniques for local drug delivery are addressed. PMID:20552308

The role of molecular imaging in diagnosis of deep vein thrombosis

PubMed Central

Houshmand, Sina; Salavati, Ali; Hess, Søren; Ravina, Mudalsha; Alavi, Abass

2014-01-01

Venous thromboembolism (VTE) mostly presenting as deep venous thrombosis (DVT) and pulmonary embolism (PE) affects up to 600,000 individuals in United States each year. Clinical symptoms of VTE are nonspecific and sometimes misleading. Additionally, side effects of available treatment plans for DVT are significant. Therefore, medical imaging plays a crucial role in proper diagnosis and avoidance from over/under diagnosis, which exposes the patient to risk. In addition to conventional structural imaging modalities, such as ultrasonography and computed tomography, molecular imaging with different tracers have been studied for diagnosis of DVT. In this review we will discuss currently available and newly evolving targets and tracers for detection of DVT using molecular imaging methods. PMID:25143860

Intraoperative Molecular Imaging of Lung Adenocarcinoma Can Identify Residual Tumor Cells at the Surgical Margins

PubMed Central

Keating, Jane J.; Okusanya, Olugbenga T.; De Jesus, Elizabeth; Judy, Ryan; Jiang, Jack; Deshpande, Charuhas; Nie, Shuming; Low, Philip; Singhal, Sunil

2017-01-01

Purpose During lung surgery, identification of surgical margins is challenging. We hypothesized that molecular imaging with a fluorescent probe to pulmonary adenocarcinomas could enhance residual tumor during resection. Procedures Mice with flank tumors received a contrast agent targeting folate receptor alpha. Optimal dose and time of injection was established. Margin detection was compared using traditional methods versus molecular imaging. A pilot study was then performed in 3 humans with lung adenocarcinoma. Results The peak tumor-to background ratio (TBR) of murine tumors was 3.9. Fluorescence peaked at 2 hours and was not improved beyond 0.1 mg/kg. Traditional inspection identified 30% of mice with positive margins. Molecular imaging identified an additional 50% of residual tumor deposits (P<0.05). The fluorescent probe visually enhanced all human tumors with a mean TBR of 3.5. Conclusions Molecular imaging is an important adjunct to traditional inspection to identify surgical margins after tumor resection. PMID:26228697

Molecular Imaging of Neuropsychiatric Symptoms in Alzheimer’s and Parkinson’s disease

PubMed Central

Hirao, Kentaro; Pontone, Gregory M.; Smith, Gwenn S.

2015-01-01

Neuropsychiatric symptoms (NPS) are very common in neurodegenerative diseases and are a major contributor to disability and caregiver burden. There is accumulating evidence that NPS may be a prodrome of neurodegenerative diseases and are associated with functional decline. The medications used to treat these symptoms in younger patients are not very effective in patients with neurodegenerative disease and may have serious side effects. An understanding of the neurobiology of NPS is critical for the development of more effective intervention strategies. Targeting these symptoms may also have implications for prevention of cognitive or motor decline. Molecular brain imaging represents a bridge between basic and clinical observations and provides many opportunities for translation from animal models and human post-mortem studies to in vivo human studies. Molecular brain imaging studies in Alzheimer’s disease (AD) and Parkinson’s disease (PD) are reviewed with a primary focus on positron emission tomography studies of NPS. Future directions for the field of molecular imaging in AD and PD to understand the neurobiology of NPS will be discussed. PMID:25446948

Bioresponsive probes for molecular imaging: concepts and in vivo applications.

PubMed

van Duijnhoven, Sander M J; Robillard, Marc S; Langereis, Sander; Grüll, Holger

2015-01-01

Molecular imaging is a powerful tool to visualize and characterize biological processes at the cellular and molecular level in vivo. In most molecular imaging approaches, probes are used to bind to disease-specific biomarkers highlighting disease target sites. In recent years, a new subset of molecular imaging probes, known as bioresponsive molecular probes, has been developed. These probes generally benefit from signal enhancement at the site of interaction with its target. There are mainly two classes of bioresponsive imaging probes. The first class consists of probes that show direct activation of the imaging label (from "off" to "on" state) and have been applied in optical imaging and magnetic resonance imaging (MRI). The other class consists of probes that show specific retention of the imaging label at the site of target interaction and these probes have found application in all different imaging modalities, including photoacoustic imaging and nuclear imaging. In this review, we present a comprehensive overview of bioresponsive imaging probes in order to discuss the various molecular imaging strategies. The focus of the present article is the rationale behind the design of bioresponsive molecular imaging probes and their potential in vivo application for the detection of endogenous molecular targets in pathologies such as cancer and cardiovascular disease. Copyright © 2015 John Wiley & Sons, Ltd.

Indocyanine Green Enables Near-Infrared Fluorescence Imaging of Lipid-Rich, Inflamed Atherosclerotic Plaques

PubMed Central

Vinegoni, Claudio; Botnaru, Ion; Aikawa, Elena; Calfon, Marcella A.; Iwamoto, Yoshiko; Folco, Eduardo J.; Ntziachristos, Vasilis; Weissleder, Ralph; Libby, Peter; Jaffer, Farouc A.

2011-01-01

New high-resolution molecular and structural imaging strategies are needed to visualize high-risk plaques that are likely to cause acute myocardial infarction, because current diagnostic methods do not reliably identify at-risk subjects. While molecular imaging agents are available for lower-resolution detection of atherosclerosis in large arteries, a lack of imaging agents coupled to high-resolution modalities has limited molecular imaging of atherosclerosis in the smaller coronary arteries [AU: ok? YES]. Here, we have demonstrated that indocyanine green (ICG), an FDA-approved near-infrared fluorescence (NIRF) emitting compound, targets atheromas within 20 minutes of injection and provides sufficient signal enhancement for in vivo detection of lipid-rich, inflamed, coronary-sized plaques in atherosclerotic rabbits. In vivo NIRF sensing was achieved with an intravascular wire in the aortae, a vessel of comparable caliber to human coronary arteries. Ex vivo fluorescence reflectance imaging studies showed high plaque target-to-background ratios in atheroma-bearing rabbits injected with ICG, compared to atheroma-bearing rabbits injected with saline. In vitro studies using human macrophages established that ICG preferentially targets lipid-loaded macrophages. In an early clinical study of human atheroma specimens from four patients, we found that ICG colocalized with plaque macrophages and lipids. The atheroma-targeting capability of ICG has the potential to accelerate the clinical development of NIRF molecular imaging of high-risk plaques in humans. PMID:21613624

Improved tumor identification using dual tracer molecular imaging in fluorescence guided brain surgery

NASA Astrophysics Data System (ADS)

Xu, Xiaochun; Torres, Veronica; Straus, David; Brey, Eric M.; Byrne, Richard W.; Tichauer, Kenneth M.

2015-03-01

Brain tumors represent a leading cause of cancer death for people under the age of 40 and the probability complete surgical resection of brain tumors remains low owing to the invasive nature of these tumors and the consequences of damaging healthy brain tissue. Molecular imaging is an emerging approach that has the potential to improve the ability for surgeons to correctly discriminate between healthy and cancerous tissue; however, conventional molecular imaging approaches in brain suffer from significant background signal in healthy tissue or an inability target more invasive sections of the tumor. This work presents initial studies investigating the ability of novel dual-tracer molecular imaging strategies to be used to overcome the major limitations of conventional "single-tracer" molecular imaging. The approach is evaluated in simulations and in an in vivo mice study with animals inoculated orthotopically using fluorescent human glioma cells. An epidermal growth factor receptor (EGFR) targeted Affibody-fluorescent marker was employed as a targeted imaging agent, and the suitability of various FDA approved untargeted fluorescent tracers (e.g. fluorescein & indocyanine green) were evaluated in terms of their ability to account for nonspecific uptake and retention of the targeted imaging agent. Signal-to-background ratio was used to measure and compare the amount of reporter in the tissue between targeted and untargeted tracer. The initial findings suggest that FDA-approved fluorescent imaging agents are ill-suited to act as untargeted imaging agents for dual-tracer fluorescent guided brain surgery as they suffer from poor delivery to the healthy brain tissue and therefore cannot be used to identify nonspecific vs. specific uptake of the targeted imaging agent where current surgery is most limited.

Ultrasound guided fluorescence molecular tomography with improved quantification by an attenuation compensated born-normalization and in vivo preclinical study of cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Baoqiang; Berti, Romain; Abran, Maxime

2014-05-15

Ultrasound imaging, having the advantages of low-cost and non-invasiveness over MRI and X-ray CT, was reported by several studies as an adequate complement to fluorescence molecular tomography with the perspective of improving localization and quantification of fluorescent molecular targets in vivo. Based on the previous work, an improved dual-modality Fluorescence-Ultrasound imaging system was developed and then validated in imaging study with preclinical tumor model. Ultrasound imaging and a profilometer were used to obtain the anatomical prior information and 3D surface, separately, to precisely extract the tissue boundary on both sides of sample in order to achieve improved fluorescence reconstruction. Furthermore,more » a pattern-based fluorescence reconstruction on the detection side was incorporated to enable dimensional reduction of the dataset while keeping the useful information for reconstruction. Due to its putative role in the current imaging geometry and the chosen reconstruction technique, we developed an attenuation compensated Born-normalization method to reduce the attenuation effects and cancel off experimental factors when collecting quantitative fluorescence datasets over large area. Results of both simulation and phantom study demonstrated that fluorescent targets could be recovered accurately and quantitatively using this reconstruction mechanism. Finally, in vivo experiment confirms that the imaging system associated with the proposed image reconstruction approach was able to extract both functional and anatomical information, thereby improving quantification and localization of molecular targets.« less

Iron Oxide Nanoradiomaterials: Combining Nanoscale Properties with Radioisotopes for Enhanced Molecular Imaging

PubMed Central

Pellico, Juan; Fernández-Barahona, Irene; Bhavesh, Riju; Ruiz-Cabello, Jesús

2017-01-01

The combination of the size-dependent properties of nanomaterials with radioisotopes is emerging as a novel tool for molecular imaging. There are numerous examples already showing how the controlled synthesis of nanoparticles and the incorporation of a radioisotope in the nanostructure offer new features beyond the simple addition of different components. Among the different nanomaterials, iron oxide-based nanoparticles are the most used in imaging because of their versatility. In this review, we will study the different radioisotopes for biomedical imaging, how to incorporate them within the nanoparticles, and what applications they can be used for. Our focus is directed towards what is new in this field, what the nanoparticles can offer to the field of nuclear imaging, and the radioisotopes hybridized with nanomaterials for use in molecular imaging. PMID:29358900

Magnetic nanoparticles as contrast agents for molecular imaging in medicine

NASA Astrophysics Data System (ADS)

O'Donnell, Matthew

2018-05-01

For over twenty years, superparamagnetic nanoparticles have been developed for a number of medical applications ranging from bioseparations, magnetic drug targeting, hyperthermia and imaging. Recent studies have shown that they can be functionalized for in vivo biological targeting, potentially enabling nanoagents for molecular imaging and site-localized drug delivery. Here we review several imaging technologies developed using functionalized superparamagnetic iron oxide nanoparticles (SPIONs) as targeted molecular agents. Several imaging modalities have exploited the large induced magnetic moment of SPIONs to create local mechanical force. Magnetic force microscopy can probe nanoparticle uptake in single cells. For in vivo applications, magnetomotive modulation of primary images in ultrasound (US), photoacoustics (PA), and optical coherence tomography (OCT) can help identify very small concentrations of nanoagents while simultaneously suppressing intrinsic background signals from tissue.

Dose reduction in molecular breast imaging

NASA Astrophysics Data System (ADS)

Wagenaar, Douglas J.; Chowdhury, Samir; Hugg, James W.; Moats, Rex A.; Patt, Bradley E.

2011-10-01

Molecular Breast Imaging (MBI) is the imaging of radiolabeled drugs, cells, or nanoparticles for breast cancer detection, diagnosis, and treatment. Screening of broad populations of women for breast cancer with mammography has been augmented by the emergence of breast MRI in screening of women at high risk for breast cancer. Screening MBI may benefit the sub-population of women with dense breast tissue that obscures small tumors in mammography. Dedicated breast imaging equipment is necessary to enable detection of early-stage tumors less than 1 cm in size. Recent progress in the development of these instruments is reviewed. Pixellated CZT for single photon MBI imaging of 99mTc-sestamibi gives high detection sensitivity for early-stage tumors. The use of registered collimators in a near-field geometry gives significantly higher detection efficiency - a factor of 3.6-, which translates into an equivalent dose reduction factor given the same acquisition time. The radiation dose in the current MBI procedure has been reduced to the level of a four-view digital mammography study. In addition to screening of selected sub-populations, reduced MBI dose allows for dual-isotope, treatment planning, and repeated therapy assessment studies in the era of molecular medicine guided by quantitative molecular imaging.

Imaging molecular dynamics in vivo--from cell biology to animal models.

PubMed

Timpson, Paul; McGhee, Ewan J; Anderson, Kurt I

2011-09-01

Advances in fluorescence microscopy have enabled the study of membrane diffusion, cell adhesion and signal transduction at the molecular level in living cells grown in culture. By contrast, imaging in living organisms has primarily been restricted to the localization and dynamics of cells in tissues. Now, imaging of molecular dynamics is on the cusp of progressing from cell culture to living tissue. This transition has been driven by the understanding that the microenvironment critically determines many developmental and pathological processes. Here, we review recent progress in fluorescent protein imaging in vivo by drawing primarily on cancer-related studies in mice. We emphasize the need for techniques that can be easily combined with genetic models and complement fluorescent protein imaging by providing contextual information about the cellular environment. In this Commentary we will consider differences between in vitro and in vivo experimental design and argue for an approach to in vivo imaging that is built upon the use of intermediate systems, such as 3-D and explant culture models, which offer flexibility and control that is not always available in vivo. Collectively, these methods present a paradigm shift towards the molecular-level investigation of disease and therapy in animal models of disease.

Molecular Imaging: FDG-PET and a whole lot more

PubMed Central

Peterson, Todd E.; Manning, H. Charles

2010-01-01

The intention of this review is to provide information about the rapidly evolving field of molecular imaging and its potential impact on the clinical practice of nuclear medicine. Upon completing this article the reader should be able to 1) define molecular imaging, 2) describe the ways in which molecular imaging can be used, 3) identify some of the biological processes that can be targeted with molecular imaging agents, and 4) list the modalities that can be used for molecular imaging along with the strengths and weaknesses of each. PMID:19692452

Searching for non-genetic molecular and imaging PTSD risk and resilience markers: Systematic review of literature and design of the German Armed Forces PTSD biomarker study.

PubMed

Schmidt, Ulrike; Willmund, Gerd-Dieter; Holsboer, Florian; Wotjak, Carsten T; Gallinat, Jürgen; Kowalski, Jens T; Zimmermann, Peter

2015-01-01

Biomarkers allowing the identification of individuals with an above average vulnerability or resilience for posttraumatic stress disorder (PTSD) would especially serve populations at high risk for trauma exposure like firefighters, police officers and combat soldiers. Aiming to identify the most promising putative PTSD vulnerability markers, we conducted the first systematic review on potential imaging and non-genetic molecular markers for PTSD risk and resilience. Following the PRISMA guidelines, we systematically screened the PubMed database for prospective longitudinal clinical studies and twin studies reporting on pre-trauma and post-trauma PTSD risk and resilience biomarkers. Using 25 different combinations of search terms, we retrieved 8151 articles of which we finally included and evaluated 9 imaging and 27 molecular studies. In addition, we briefly illustrate the design of the ongoing prospective German Armed Forces (Bundeswehr) PTSD biomarker study (Bw-BioPTSD) which not only aims to validate these previous findings but also to identify novel and clinically applicable molecular, psychological and imaging risk, resilience and disease markers for deployment-related psychopathology in a cohort of German soldiers who served in Afghanistan. Copyright © 2014 Elsevier Ltd. All rights reserved.

[Microdose clinical trial--impact of PET molecular imaging].

PubMed

Yano, Tsuneo; Watanabe, Yasuyoshi

2010-10-01

Microdose (MD) clinical trial and exploratory IND study including sub-therapeutic dose and therapeutic dose which are higher than microdoses are expected to bring about innovations in drug development. The outlines of guidances for microdose clinical trial and ICH-M3 (R2) issued by the MHLW in June, 2008, and February, 2010, are first explained, respectively, and some examples of their application to clinical developments of therapeutic drugs in the infection and cancer fields are introduced. Especially, thanks to the progress of molecular imaging research, a new field of drug development is explored by using imaging biomarkers for efficacy or safety evaluation which visualize biomarkers by PET imaging agents. Finally, the roadmap for drug development in infection and cancer fields utilizing PET molecular imaging is discussed.

Tumor invasion unit in gastric cancer revealed by QDs-based in situ molecular imaging and multispectral analysis.

PubMed

Hu, Wen-Qing; Fang, Min; Zhao, Hao-Liang; Yan, Shu-Guang; Yuan, Jing-Ping; Peng, Chun-Wei; Yang, Gui-Fang; Li, Yan; Li, Jian-Ding

2014-04-01

In tumor tissues, cancer cells, tumor infiltrating macrophages and tumor neo-vessels in close spatial vicinity with one another form tumor invasion unit, which is a biologically important tumor microenvironment of metastasis to facilitate cancer invasion and metastasis. Establishing an in situ molecular imaging technology to simultaneously reveal these three components is essential for the in-depth investigation of tumor invasion unit. In this report, we have developed a computer-aided algorithm by quantum dots (QDs)-based multiplexed molecular imaging technique for such purpose. A series of studies on gastric cancer tumor tissues demonstrated that the tumor invasion unit was correlated with major unfavorable pathological features and worse clinical outcomes, which illustrated the significantly negative impacts and predictive power of tumor invasion unit on patient overall survival. This study confirmed the technical advantages of QDs-based in situ and simultaneous molecular imaging of key cancer molecules to gain deeper insights into the biology of cancer invasion. Copyright © 2014 Elsevier Ltd. All rights reserved.

Molecular breast imaging using a dedicated high-performance instrument

NASA Astrophysics Data System (ADS)

O'Connor, Michael K.; Wagenaar, Douglas; Hruska, Carrie B.; Phillips, Stephen; Caravaglia, Gina; Rhodes, Deborah

2006-08-01

In women with radiographically dense breasts, the sensitivity of mammography is less than 50%. With the increase in the percent of women with dense breasts, it is important to look at alternative screening techniques for this population. This article reviews the strengths and weaknesses of current imaging techniques and focuses on recent developments in semiconductor-based gamma camera systems that offer significant improvements in image quality over that achievable with single-crystal sodium iodide systems. We have developed a technique known as Molecular Breast Imaging (MBI) using small field of view Cadmium Zinc Telluride (CZT) gamma cameras that permits the breast to be imaged in a similar manner to mammography, using light pain-free compression. Computer simulations and experimental studies have shown that use of low-energy high sensitivity collimation coupled with the excellent energy resolution and intrinsic spatial resolution of CZT detectors provides optimum image quality for the detection of small breast lesions. Preliminary clinical studies with a prototype dual-detector system have demonstrated that Molecular Breast Imaging has a sensitivity of ~90% for the detection of breast tumors less than 10 mm in diameter. By comparison, conventional scintimammography only achieves a sensitivity of 50% in the detection of lesions < 10 mm. Because Molecular Breast Imaging is not affected by breast density, this technique may offer an important adjunct to mammography in the evaluation of women with dense breast parenchyma.

Molecular Imaging of Conscious, Unrestrained Mice with AwakeSPECT

DOE Office of Scientific and Technical Information (OSTI.GOV)

Baba, Justin S; Endres, Christopher; Foss, Catherine

2013-01-01

We have developed a SPECT imaging system, AwakeSPECT, to enable molecular brain imaging of untrained mice that are conscious, unanesthetized, and unrestrained. We accomplished this with head tracking and motion correction techniques. Methods: The capability of the system for motion-corrected imaging was demonstrated with a 99mTc-pertechnetate phantom, 99mTcmethylene diphosphonate bone imaging, and measurement of the binding potential of the dopamine transporter radioligand 123I-ioflupane in mouse brain in the awake and anesthetized (isoflurane) states. Stress induced by imaging in the awake state was assessed through measurement of plasma corticosterone levels. Results: AwakeSPECT provided high-resolution bone images reminiscent of those obtained frommore » CT. The binding potential of 123I-ioflupane in the awake state was on the order of 50% of that obtained with the animal under anesthesia, consistent with previous studies in nonhuman primates. Levels of stress induced were on the order of those seen in other behavioral tasks and imaging studies of awake animals. Conclusion: These results demonstrate the feasibility of SPECT molecular brain imaging of mice in the conscious, unrestrained state and demonstrate the effects of isoflurane anesthesia on radiotracer uptake.« less

Molecular Imaging of Conscious, Unrestrained Mice with AwakeSPECT

DOE Office of Scientific and Technical Information (OSTI.GOV)

Baba, Justin S.; Endres, Christopher J.; Foss, Catherine A.

2013-06-01

We have developed a SPECT imaging system, AwakeSPECT, to enable molecular brain imaging of untrained mice that are conscious, unanesthetized, and unrestrained. We accomplished this with head tracking and motion correction techniques. Methods: The capability of the system for motion-corrected imaging was demonstrated with a ^99mTc-pertechnetate phantom, ^99mTc-methylene diphosphonate bone imaging, and measurement of the binding potential of the dopamine transporter radioligand ^123I-ioflupane in mouse brain in the awake and anesthetized (isoflurane) states. Stress induced by imaging in the awake state was assessed through measurement of plasma corticosterone levels. Results: AwakeSPECT provided high-resolution bone images reminiscent of those obtained frommore » CT. The binding potential of ^123I-ioflupane in the awake state was on the order of 50% of that obtained with the animal under anesthesia, consistent with previous studies in nonhuman primates. Levels of stress induced were on the order of those seen in other behavioral tasks and imaging studies of awake animals. Conclusion: These results demonstrate the feasibility of SPECT molecular brain imaging of mice in the conscious, unrestrained state and demonstrate the effects of isoflurane anesthesia on radiotracer uptake.« less

Imaging Alzheimer's disease pathophysiology with PET

PubMed Central

Schilling, Lucas Porcello; Zimmer, Eduardo R.; Shin, Monica; Leuzy, Antoine; Pascoal, Tharick A.; Benedet, Andréa L.; Borelli, Wyllians Vendramini; Palmini, André; Gauthier, Serge; Rosa-Neto, Pedro

2016-01-01

ABSTRACT Alzheimer's disease (AD) has been reconceptualised as a dynamic pathophysiological process characterized by preclinical, mild cognitive impairment (MCI), and dementia stages. Positron emission tomography (PET) associated with various molecular imaging agents reveals numerous aspects of dementia pathophysiology, such as brain amyloidosis, tau accumulation, neuroreceptor changes, metabolism abnormalities and neuroinflammation in dementia patients. In the context of a growing shift toward presymptomatic early diagnosis and disease-modifying interventions, PET molecular imaging agents provide an unprecedented means of quantifying the AD pathophysiological process, monitoring disease progression, ascertaining whether therapies engage their respective brain molecular targets, as well as quantifying pharmacological responses. In the present study, we highlight the most important contributions of PET in describing brain molecular abnormalities in AD. PMID:29213438

Recent Developments in Molecular Brain Imaging of Neuropsychiatric Disorders.

PubMed

Slifstein, Mark; Abi-Dargham, Anissa

2017-01-01

Molecular imaging with PET or SPECT has been an important research tool in psychiatry for as long as these modalities have been available. Here, we discuss two areas of neuroimaging relevant to current psychiatry research. The first is the use of imaging to study neurotransmission. We discuss the use of pharmacologic probes to induce changes in levels of neurotransmitters that can be inferred through their effects on outcome measures of imaging experiments, from their historical origins focusing on dopamine transmission through recent developments involving serotonin, GABA, and glutamate. Next, we examine imaging of neuroinflammation in the context of psychiatry. Imaging markers of neuroinflammation have been studied extensively in other areas of brain research, but they have more recently attracted interest in psychiatry research, based on accumulating evidence that there may be an inflammatory component to some psychiatric conditions. Furthermore, new probes are under development that would allow unprecedented insights into cellular processes. In summary, molecular imaging would continue to offer great potential as a unique tool to further our understanding of brain function in health and disease. Copyright © 2017 Elsevier Inc. All rights reserved.

Construction of specific magnetic resonance imaging/optical dual-modality molecular probe used for imaging angiogenesis of gastric cancer.

PubMed

Yan, Xuejie; Song, Xiaoyan; Wang, Zhenbo

2017-05-01

The purpose of the study was to construct specific magnetic resonance imaging (MRI)/optical dual-modality molecular probe. Tumor-bearing animal models were established. MRI/optical dual-modality molecular probe was construed by coupling polyethylene glycol (PEG)-modified nano-Fe 3 O 4 with specific targeted cyclopeptide GX1 and near-infrared fluorescent dyes Cy5.5. MRI/optical imaging effects of the probe were observed and the feasibility of in vivo double-modality imaging was discussed. It was found that, the double-modality probe was of high stability; tumor signal of the experimental group tended to be weak after injection of the probe, but rose to a level which was close to the previous level after 18 h (p > 0.05). We successively completed the construction of an ideal MRI/optical dual-modality molecular probe. MRI/optical dual-modality molecular probe which can selectively gather in gastric cancer is expected to be a novel probe used for diagnosing gastric cancer in the early stage.

Oligometastatic prostate cancer: shaping the definition with molecular imaging and an improved understanding of tumor biology.

PubMed

Joice, Gregory A; Rowe, Steven P; Pienta, Kenneth J; Gorin, Michael A

2017-11-01

The aim of this review is to discuss how novel imaging modalities and molecular markers are shaping the definition of oligometastatic prostate cancer. To effectively classify a patient as having oligometastatic prostate cancer, diagnostic tests must be sensitive enough to detect subtle sites of metastatic disease. Conventional imaging modalities can readily detect widespread polymetastatic disease but do not have the sensitivity necessary to reliably classify patients as oligometastatic. Molecular imaging using both metabolic- and molecularly-targeted radiotracers has demonstrated great promise in aiding in our ability to define the oligometastatic state. Perhaps the most promising data to date have been generated with radiotracers targeting prostate-specific membrane antigen. In addition, early studies are beginning to define biologic markers in the oligometastatic state that may be indicative of disease with minimal metastatic potential. Recent developments in molecular imaging have allowed for improved detection of metastatic prostate cancer allowing for more accurate staging of patients with oligometastatic disease. Future development of biologic markers may assist in defining the oligometastatic state and determining prognosis.

Magnetomotive Molecular Nanoprobes

PubMed Central

John, Renu; Boppart, Stephen A.

2012-01-01

Tremendous developments in the field of biomedical imaging in the past two decades have resulted in the transformation of anatomical imaging to molecular-specific imaging. The main approaches towards imaging at a molecular level are the development of high resolution imaging modalities with high penetration depths and increased sensitivity, and the development of molecular probes with high specificity. The development of novel molecular contrast agents and their success in molecular optical imaging modalities have lead to the emergence of molecular optical imaging as a more versatile and capable technique for providing morphological, spatial, and functional information at the molecular level with high sensitivity and precision, compared to other imaging modalities. In this review, we discuss a new class of dynamic contrast agents called magnetomotive molecular nanoprobes for molecular-specific imaging. Magnetomotive agents are superparamagnetic nanoparticles, typically iron-oxide, that are physically displaced by the application of a small modulating external magnetic field. Dynamic phase-sensitive position measurements are performed using any high resolution imaging modality, including optical coherence tomography (OCT), ultrasonography, or magnetic resonance imaging (MRI). The dynamics of the magnetomotive agents can be used to extract the biomechanical tissue properties in which the nanoparticles are bound, and the agents can be used to deliver therapy via magnetomotive displacements to modulate or disrupt cell function, or hyperthermia to kill cells. These agents can be targeted via conjugation to antibodies, and in vivo targeted imaging has been shown in a carcinogen-induced rat mammary tumor model. The iron-oxide nanoparticles also exhibit negative T2 contrast in MRI, and modulations can produce ultrasound imaging contrast for multimodal imaging applications. PMID:21517766

Preparation of a Versatile Bifunctional Zeolite for Targeted Imaging Applications

PubMed Central

Ndiege, Nicholas; Raidoo, Renugan; Schultz, Michael K.; Larsen, Sarah

2011-01-01

Bifunctional zeolite Y was prepared for use in targeted in vivo molecular imaging applications. The strategy involved functionalization of the external surface of zeolite Y with chloropropyltriethoxysilane followed by reaction with sodium azide to form azide-functionalized NaY, which is amenable to copper(1) catalyzed click chemistry. In this study, a model alkyne (4-pentyn-1-ol) was attached to the azide-terminated surface via click chemistry to demonstrate feasibility for attachment of molecular targeting vectors (e.g., peptides, aptamers) to the zeolite surface. The modified particle efficiently incorporates the imaging radioisotope gallium-68 (68Ga) into the pores of the azide-functionalized NaY zeolite to form a stable bifunctional molecular targeting vector. The result is a versatile “clickable” zeolite platform that can be tailored for future in vivo molecular targeting and imaging modalities. PMID:21306141

The role of amino acid PET in the light of the new WHO classification 2016 for brain tumors.

PubMed

Suchorska, Bogdana; Albert, Nathalie L; Bauer, Elena K; Tonn, Jörg-Christian; Galldiks, Norbert

2018-04-26

Since its introduction in 2016, the revision of the World Health Organization (WHO) classification of central nervous system tumours has already changed the diagnostic and therapeutic approach in glial tumors. Blurring the lines between entities formerly labelled as "high-grade" or "low-grade", molecular markers define distinct biological subtypes with different clinical course. This new classification raises the demand for non-invasive imaging methods focussing on depicting metabolic processes. We performed a review of current literature on the use of amino acid PET (AA-PET) for obtaining diagnostic or prognostic information on glioma in the setting of the current WHO 2016 classification. So far, only a few studies have focussed on combining molecular genetic information and metabolic imaging using AA-PET. The current review summarizes the information available on "molecular grading" as well as prognostic information obtained from AA-PET and delivers an insight into a possible interrelation between metabolic imaging and glioma genetics. Within the framework of molecular characterization of gliomas, metabolic imaging using AA-PET is a promising tool for non-invasive characterisation of molecular features and to provide additional prognostic information. Further studies incorporating molecular and metabolic features are necessary to improve the explanatory power of AA-PET in glial tumors.

Molecular Imaging in the Era of Personalized Medicine

PubMed Central

Jung, Kyung-Ho; Lee, Kyung-Han

2015-01-01

Clinical imaging creates visual representations of the body interior for disease assessment. The role of clinical imaging significantly overlaps with that of pathology, and diagnostic workflows largely depend on both fields. The field of clinical imaging is presently undergoing a radical change through the emergence of a new field called molecular imaging. This new technology, which lies at the intersection between imaging and molecular biology, enables noninvasive visualization of biochemical processes at the molecular level within living bodies. Molecular imaging differs from traditional anatomical imaging in that biomarkers known as imaging probes are used to visualize target molecules-of-interest. This ability opens up exciting new possibilities for applications in oncologic, neurological and cardiovascular diseases. Molecular imaging is expected to make major contributions to personalized medicine by allowing earlier diagnosis and predicting treatment response. The technique is also making a huge impact on pharmaceutical development by optimizing preclinical and clinical tests for new drug candidates. This review will describe the basic principles of molecular imaging and will briefly touch on three examples (from an immense list of new techniques) that may contribute to personalized medicine: receptor imaging, angiogenesis imaging, and apoptosis imaging. PMID:25812652

Molecular imaging in the era of personalized medicine.

PubMed

Jung, Kyung-Ho; Lee, Kyung-Han

2015-01-01

Clinical imaging creates visual representations of the body interior for disease assessment. The role of clinical imaging significantly overlaps with that of pathology, and diagnostic workflows largely depend on both fields. The field of clinical imaging is presently undergoing a radical change through the emergence of a new field called molecular imaging. This new technology, which lies at the intersection between imaging and molecular biology, enables noninvasive visualization of biochemical processes at the molecular level within living bodies. Molecular imaging differs from traditional anatomical imaging in that biomarkers known as imaging probes are used to visualize target molecules-of-interest. This ability opens up exciting new possibilities for applications in oncologic, neurological and cardiovascular diseases. Molecular imaging is expected to make major contributions to personalized medicine by allowing earlier diagnosis and predicting treatment response. The technique is also making a huge impact on pharmaceutical development by optimizing preclinical and clinical tests for new drug candidates. This review will describe the basic principles of molecular imaging and will briefly touch on three examples (from an immense list of new techniques) that may contribute to personalized medicine: receptor imaging, angiogenesis imaging, and apoptosis imaging.

Cells from icons to symbols: molecularizing cell biology in the 1980s.

PubMed

Serpente, Norberto

2011-12-01

Over centuries cells have been the target of optical and electronic microscopes as well as others technologies, with distinctive types of visual output. Whilst optical technologies produce images 'evident to the eye', the electronic and especially the molecular create images that are more elusive to conceptualization and assessment. My study applies the semiotic approach to the production of images in cell biology to capture the shift from microscopic images to non-traditional visual technologies around 1980. Here I argue that the visual shift that coincides with the growing dominance of molecular biology involves a change from iconic to symbolic forms. Copyright © 2011 Elsevier Ltd. All rights reserved.

Integration of Network Biology and Imaging to Study Cancer Phenotypes and Responses.

PubMed

Tian, Ye; Wang, Sean S; Zhang, Zhen; Rodriguez, Olga C; Petricoin, Emanuel; Shih, Ie-Ming; Chan, Daniel; Avantaggiati, Maria; Yu, Guoqiang; Ye, Shaozhen; Clarke, Robert; Wang, Chao; Zhang, Bai; Wang, Yue; Albanese, Chris

2014-01-01

Ever growing "omics" data and continuously accumulated biological knowledge provide an unprecedented opportunity to identify molecular biomarkers and their interactions that are responsible for cancer phenotypes that can be accurately defined by clinical measurements such as in vivo imaging. Since signaling or regulatory networks are dynamic and context-specific, systematic efforts to characterize such structural alterations must effectively distinguish significant network rewiring from random background fluctuations. Here we introduced a novel integration of network biology and imaging to study cancer phenotypes and responses to treatments at the molecular systems level. Specifically, Differential Dependence Network (DDN) analysis was used to detect statistically significant topological rewiring in molecular networks between two phenotypic conditions, and in vivo Magnetic Resonance Imaging (MRI) was used to more accurately define phenotypic sample groups for such differential analysis. We applied DDN to analyze two distinct phenotypic groups of breast cancer and study how genomic instability affects the molecular network topologies in high-grade ovarian cancer. Further, FDA-approved arsenic trioxide (ATO) and the ND2-SmoA1 mouse model of Medulloblastoma (MB) were used to extend our analyses of combined MRI and Reverse Phase Protein Microarray (RPMA) data to assess tumor responses to ATO and to uncover the complexity of therapeutic molecular biology.

Imaging of DNA and Protein by SFM and Combined SFM-TIRF Microscopy.

PubMed

Grosbart, Małgorzata; Ristić, Dejan; Sánchez, Humberto; Wyman, Claire

2018-01-01

Direct imaging is invaluable for understanding the mechanism of complex genome transactions where proteins work together to organize, transcribe, replicate and repair DNA. Scanning (or atomic) force microscopy is an ideal tool for this, providing 3D information on molecular structure at nm resolution from defined components. This is a convenient and practical addition to in vitro studies as readily obtainable amounts of purified proteins and DNA are required. The images reveal structural details on the size and location of DNA bound proteins as well as protein-induced arrangement of the DNA, which are directly correlated in the same complexes. In addition, even from static images, the different forms observed and their relative distributions can be used to deduce the variety and stability of different complexes that are necessarily involved in dynamic processes. Recently available instruments that combine fluorescence with topographic imaging allow the identification of specific molecular components in complex assemblies, which broadens the applications and increases the information obtained from direct imaging of molecular complexes. We describe here basic methods for preparing samples of proteins, DNA and complexes of the two for topographic imaging and quantitative analysis. We also describe special considerations for combined fluorescence and topographic imaging of molecular complexes.

Sample preparation for SFM imaging of DNA, proteins, and DNA-protein complexes.

PubMed

Ristic, Dejan; Sanchez, Humberto; Wyman, Claire

2011-01-01

Direct imaging is invaluable for understanding the mechanism of complex genome transactions where proteins work together to organize, transcribe, replicate, and repair DNA. Scanning (or atomic) force microscopy is an ideal tool for this, providing 3D information on molecular structure at nanometer resolution from defined components. This is a convenient and practical addition to in vitro studies as readily obtainable amounts of purified proteins and DNA are required. The images reveal structural details on the size and location of DNA-bound proteins as well as protein-induced arrangement of the DNA, which are directly correlated in the same complexes. In addition, even from static images, the different forms observed and their relative distributions can be used to deduce the variety and stability of different complexes that are necessarily involved in dynamic processes. Recently available instruments that combine fluorescence with topographic imaging allow the identification of specific molecular components in complex assemblies, which broadens the applications and increases the information obtained from direct imaging of molecular complexes. We describe here basic methods for preparing samples of proteins, DNA, and complexes of the two for topographic imaging and quantitative analysis. We also describe special considerations for combined fluorescence and topographic imaging of molecular complexes.

New Researches and Application Progress of Commonly Used Optical Molecular Imaging Technology

PubMed Central

Chen, Zhi-Yi; Yang, Feng; Lin, Yan; Zhou, Qiu-Lan; Liao, Yang-Ying

2014-01-01

Optical molecular imaging, a new medical imaging technique, is developed based on genomics, proteomics and modern optical imaging technique, characterized by non-invasiveness, non-radiativity, high cost-effectiveness, high resolution, high sensitivity and simple operation in comparison with conventional imaging modalities. Currently, it has become one of the most widely used molecular imaging techniques and has been applied in gene expression regulation and activity detection, biological development and cytological detection, drug research and development, pathogenesis research, pharmaceutical effect evaluation and therapeutic effect evaluation, and so forth, This paper will review the latest researches and application progresses of commonly used optical molecular imaging techniques such as bioluminescence imaging and fluorescence molecular imaging. PMID:24696850

Imaging the small animal cardiovascular system in real-time with multispectral optoacoustic tomography

NASA Astrophysics Data System (ADS)

Taruttis, Adrian; Herzog, Eva; Razansky, Daniel; Ntziachristos, Vasilis

2011-03-01

Multispectral Optoacoustic Tomography (MSOT) is an emerging technique for high resolution macroscopic imaging with optical and molecular contrast. We present cardiovascular imaging results from a multi-element real-time MSOT system recently developed for studies on small animals. Anatomical features relevant to cardiovascular disease, such as the carotid arteries, the aorta and the heart, are imaged in mice. The system's fast acquisition time, in tens of microseconds, allows images free of motion artifacts from heartbeat and respiration. Additionally, we present in-vivo detection of optical imaging agents, gold nanorods, at high spatial and temporal resolution, paving the way for molecular imaging applications.

Deep Learning in Nuclear Medicine and Molecular Imaging: Current Perspectives and Future Directions.

PubMed

Choi, Hongyoon

2018-04-01

Recent advances in deep learning have impacted various scientific and industrial fields. Due to the rapid application of deep learning in biomedical data, molecular imaging has also started to adopt this technique. In this regard, it is expected that deep learning will potentially affect the roles of molecular imaging experts as well as clinical decision making. This review firstly offers a basic overview of deep learning particularly for image data analysis to give knowledge to nuclear medicine physicians and researchers. Because of the unique characteristics and distinctive aims of various types of molecular imaging, deep learning applications can be different from other fields. In this context, the review deals with current perspectives of deep learning in molecular imaging particularly in terms of development of biomarkers. Finally, future challenges of deep learning application for molecular imaging and future roles of experts in molecular imaging will be discussed.

Molecular Ultrasound Imaging for the Detection of Neural Inflammation

NASA Astrophysics Data System (ADS)

Volz, Kevin R.

Molecular imaging is a form of nanotechnology that enables the noninvasive examination of biological processes in vivo. Radiopharmaceutical agents are used to selectively target biochemical markers, which permits their detection and evaluation. Early visualization of molecular variations indicative of pathophysiological processes can aid in patient diagnoses and management decisions. Molecular imaging is performed by introducing molecular probes into the body. Molecular probes are often contrast agents that have been nanoengineered to selectively target and tether to molecules, enabling their radiologic identification. Ultrasound contrast agents have been demonstrated as an effective method of detecting perfusion at the tissue level. Through a nanoengineering process, ultrasound contrast agents can be targeted to specific molecules, thereby extending ultrasound's capabilities from the tissue to molecular level. Molecular ultrasound, or targeted contrast enhanced ultrasound (TCEUS), has recently emerged as a popular molecular imaging technique due to its ability to provide real-time anatomical and functional information in the absence of ionizing radiation. However, molecular ultrasound represents a novel form of molecular imaging, and consequently remains largely preclinical. A review of the TCEUS literature revealed multiple preclinical studies demonstrating its success in detecting inflammation in a variety of tissues. Although, a gap was identified in the existing evidence, as TCEUS effectiveness for detection of neural inflammation in the spinal cord was unable to be uncovered. This gap in knowledge, coupled with the profound impacts that this TCEUS application could have clinically, provided rationale for its exploration, and use as contributory evidence for the molecular ultrasound body of literature. An animal model that underwent a contusive spinal cord injury was used to establish preclinical evidence of TCEUS to detect neural inflammation. Imaging was performed while targeting three early inflammatory markers (P-selectin, VCAM-1, ICAM-1). Imaging protocols and outcome measures of previous TCEUS investigations of inflammation were replicated to aid in comparisons of outcomes. Signal intensity data was used to generate time intensity curves for qualitative and quantitative analysis of contrast agent temporal behavior. A proof of principle study established preclinical evidence to support the ability of TCEUS to detect acute neural inflammation. Substantial increases in signal intensities were observed while targeting inflammatory markers compared to controls. Further investigations consisted of examining molecular ultrasound sensitivity, and were accomplished by examining targeted contrast agent dosing parameters, and the ability of TCEUS to longitudinally evaluate neural inflammation. Qualitative analysis of TCEUS imaging performed with both administered doses revealed marked increases in signal intensities during acute inflammation, where inflammatory marker expression was presumably at its highest. This was in comparison to measures obtained in the absence of, and during, chronic inflammation. This research contributes much needed empirical evidence to the molecular ultrasound body of literature, and represents the first steps towards advancing this TCEUS application to clinical practice. Future studies are necessary to further these findings and effectively build upon this evidence. Increasing evidence of TCEUS use for the detection of neural inflammation will aid in its eventual clinical translation, where it will likely have a positive impact on patient care.

Molecular imaging of photodynamic therapy

NASA Astrophysics Data System (ADS)

Chang, Sung K.; Errabelli, Divya; Rizvi, Imran; Solban, Nicolas; O'Riordan, Katherine; Hasan, Tayyaba

2006-02-01

Recent advances in light sources, detectors and other optical imaging technologies coupled with the development of novel optical contrast agents have enabled real-time, high resolution, in vivo monitoring of molecular targets. Noninvasive monitoring of molecular targets is particularly relevant to photodynamic therapy (PDT), including the delivery of photosensitizer in the treatment site and monitoring of molecular and physiological changes following treatment. Our lab has developed optical imaging technologies to investigate these various aspects of photodynamic therapy (PDT). We used a laser scanning confocal microscope to monitor the pharmacokinetics of various photosensitizers in in vitro as well as ex vivo samples, and developed an intravital fluorescence microscope to monitor photosensitizer delivery in vivo in small animals. A molecular specific contrast agent that targets the vascular endothelial growth factor (VEGF) was developed to monitor the changes in the protein expression following PDT. We were then able to study the physiological changes due to post-treatment VEGF upregulation by quantifying vascular permeability with in vivo imaging.

The effects of ecstasy on neurotransmitter systems: a review on the findings of molecular imaging studies.

PubMed

Vegting, Yosta; Reneman, Liesbeth; Booij, Jan

2016-10-01

Ecstasy is a commonly used psychoactive drug with 3,4-methylenedioxymethamphetamine (MDMA) as the main content. Importantly, it has been suggested that use of MDMA may be neurotoxic particularly for serotonergic (5-hydroxytryptamine (5-HT)) neurons. In the past decades, several molecular imaging studies examined directly in vivo the effects of ecstasy/MDMA on neurotransmitter systems. The objective of the present study is to review the effects of ecstasy/MDMA on neurotransmitter systems as assessed by molecular imaging studies in small animals, non-human primates and humans. A search in PubMed was performed. Eighty-eight articles were found on which inclusion and exclusion criteria were applied. Thirty-three studies met the inclusion criteria; all were focused on the 5-HT or dopamine (DA) system. Importantly, 9 out of 11 of the animal studies that examined the effects of MDMA on 5-HT transporter (SERT) availability showed a significant loss of binding potential. In human studies, this was the case for 14 out of 16 studies, particularly in heavy users. In abstinent users, significant recovery of SERT binding was found over time. Most imaging studies in humans that focused on the DA system did not find any significant effect of ecstasy/MDMA use. Preclinical and clinical molecular imaging studies on the effects of ecstasy/MDMA use/administration on neurotransmitter systems show quite consistent alterations of the 5-HT system. Particularly, in human studies, loss of SERT binding was observed in heavy ecstasy users, which might reflect 5-HT neurotoxicity, although alternative explanations (e.g. down-regulation of the SERT) cannot be excluded.

A Training Program in Breast Cancer Research Using NMR Techniques

DTIC Science & Technology

2005-07-01

to explore the application NMR molecular imaging techniques developed in this program in detection of amyloid plaques in the Alzheimer diseased mouse...one is to utilize the molecular imaging technique to exploit new application in imaging of amyloid plaques in Alzheimer disease. A abridge of each...matched, non-demented elderly suggests that volumetric studies of ante-mortem neuroimages may provide an early marker of AD in aging populations. In

18F-FDG PET imaging for identifying the dynamics of intestinal disease caused by SFTSV infection in a mouse model.

PubMed

Hayasaka, Daisuke; Nishi, Kodai; Fuchigami, Takeshi; Shiogama, Kazuya; Onouchi, Takanori; Shimada, Satoshi; Tsutsumi, Yutaka; Morita, Kouichi

2016-01-05

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging disease that causes fever, enteritis, thrombocytopenia, and leucopenia and can be fatal in up to 30% of cases. However, the mechanism of severe disease is not fully understood. Molecular imaging approaches, such as positron-emission tomography (PET), are functional in vivo imaging techniques that provide real-time dynamics of disease progression, assessments of pharmacokinetics, and diagnoses for disease progression. Molecular imaging also potentially provides useful approaches to explore the pathogenesis of viral infections. Thus, the purpose of this study was to image the pathological features of SFTSV infection in vivo by PET imaging. In a mouse model, we showed that 18F-FDG accumulations clearly identified the intestinal tract site as a pathological site. We also demonstrated that 18F-FDG PET imaging can assess disease progression and response to antiserum therapy within the same individual. This is the first report demonstrating a molecular imaging strategy for SFTSV infection. Our results provide potentially useful information for preclinical studies such as the elucidation of the mechanism of SFTSV infection in vivo and the assessment of drugs for SFTS treatment.

Imaging and Force Recognition of Single Molecular Behaviors Using Atomic Force Microscopy

PubMed Central

Li, Mi; Dang, Dan; Liu, Lianqing; Xi, Ning; Wang, Yuechao

2017-01-01

The advent of atomic force microscopy (AFM) has provided a powerful tool for investigating the behaviors of single native biological molecules under physiological conditions. AFM can not only image the conformational changes of single biological molecules at work with sub-nanometer resolution, but also sense the specific interactions of individual molecular pair with piconewton force sensitivity. In the past decade, the performance of AFM has been greatly improved, which makes it widely used in biology to address diverse biomedical issues. Characterizing the behaviors of single molecules by AFM provides considerable novel insights into the underlying mechanisms guiding life activities, contributing much to cell and molecular biology. In this article, we review the recent developments of AFM studies in single-molecule assay. The related techniques involved in AFM single-molecule assay were firstly presented, and then the progress in several aspects (including molecular imaging, molecular mechanics, molecular recognition, and molecular activities on cell surface) was summarized. The challenges and future directions were also discussed. PMID:28117741

Rational chemical design of the next generation of molecular imaging probes based on physics and biology: mixing modalities, colors and signals

PubMed Central

Longmire, Michelle R.; Ogawa, Mikako; Choyke, Peter L.

2012-01-01

In recent years, numerous in vivo molecular imaging probes have been developed. As a consequence, much has been published on the design and synthesis of molecular imaging probes focusing on each modality, each type of material, or each target disease. More recently, second generation molecular imaging probes with unique, multi-functional, or multiplexed characteristics have been designed. This critical review focuses on (i) molecular imaging using combinations of modalities and signals that employ the full range of the electromagnetic spectra, (ii) optimized chemical design of molecular imaging probes for in vivo kinetics based on biology and physiology across a range of physical sizes, (iii) practical examples of second generation molecular imaging probes designed to extract complementary data from targets using multiple modalities, color, and comprehensive signals (277 references). PMID:21607237

Molecular spectral imaging system for quantitative immunohistochemical analysis of early diabetic retinopathy.

PubMed

Li, Qingli; Zhang, Jingfa; Wang, Yiting; Xu, Guoteng

2009-12-01

A molecular spectral imaging system has been developed based on microscopy and spectral imaging technology. The system is capable of acquiring molecular spectral images from 400 nm to 800 nm with 2 nm wavelength increments. The basic principles, instrumental systems, and system calibration method as well as its applications for the calculation of the stain-uptake by tissues are introduced. As a case study, the system is used for determining the pathogenesis of diabetic retinopathy and evaluating the therapeutic effects of erythropoietin. Some molecular spectral images of retinal sections of normal, diabetic, and treated rats were collected and analyzed. The typical transmittance curves of positive spots stained for albumin and advanced glycation end products are retrieved from molecular spectral data with the spectral response calibration algorithm. To explore and evaluate the protective effect of erythropoietin (EPO) on retinal albumin leakage of streptozotocin-induced diabetic rats, an algorithm based on Beer-Lambert's law is presented. The algorithm can assess the uptake by histologic retinal sections of stains used in quantitative pathology to label albumin leakage and advanced glycation end products formation. Experimental results show that the system is helpful for the ophthalmologist to reveal the pathogenesis of diabetic retinopathy and explore the protective effect of erythropoietin on retinal cells of diabetic rats. It also highlights the potential of molecular spectral imaging technology to provide more effective and reliable diagnostic criteria in pathology.

Design Principles of Nanoparticles as Contrast Agents for Magnetic Resonance Imaging

NASA Astrophysics Data System (ADS)

Shan, Liang; Gu, Xinbin; Wang, Paul

2013-09-01

Molecular imaging is an emerging field that introduces molecular agents into traditional imaging techniques, enabling visualization, characterization and measurement of biological processes at the molecular and cellular levels in humans and other living systems. The promise of molecular imaging lies in its potential for selective potency by targeting biomarkers or molecular targets and the imaging agents serve as reporters for the selectivity of targeting. Development of an efficient molecular imaging agent depends on well-controlled high-quality experiment design involving target selection, agent synthesis, in vitro characterization, and in vivo animal characterization before it is applied in humans. According to the analysis from the Molecular Imaging and Contrast Agent Database (MICAD, ), more than 6000 molecular imaging agents with sufficient preclinical evaluation have been reported to date in the literature and this number increases by 250-300 novel agents each year. The majority of these agents are radionuclides, which are developed for positron emission tomography (PET) and single photon emission computed tomography (SPECT). Contrast agents for magnetic resonance imaging (MRI) account for only a small part. This is largely due to the fact that MRI is currently not a fully quantitative imaging technique and is less sensitive than PET and SPECT. However, because of the superior ability to simultaneously extract molecular and anatomic information, molecular MRI is attracting significant interest and various targeted nanoparticle contrast agents have been synthesized for MRI. The first and one of the most critical steps in developing a targeted nanoparticle contrast agent is target selection, which plays the central role and forms the basis for success of molecular imaging. This chapter discusses the design principles of targeted contrast agents in the emerging frontiers of molecular MRI.

Onboard functional and molecular imaging: A design investigation for robotic multipinhole SPECT

PubMed Central

Bowsher, James; Yan, Susu; Roper, Justin; Giles, William; Yin, Fang-Fang

2014-01-01

Purpose: Onboard imaging—currently performed primarily by x-ray transmission modalities—is essential in modern radiation therapy. As radiation therapy moves toward personalized medicine, molecular imaging, which views individual gene expression, may also be important onboard. Nuclear medicine methods, such as single photon emission computed tomography (SPECT), are premier modalities for molecular imaging. The purpose of this study is to investigate a robotic multipinhole approach to onboard SPECT. Methods: Computer-aided design (CAD) studies were performed to assess the feasibility of maneuvering a robotic SPECT system about a patient in position for radiation therapy. In order to obtain fast, high-quality SPECT images, a 49-pinhole SPECT camera was designed which provides high sensitivity to photons emitted from an imaging region of interest. This multipinhole system was investigated by computer-simulation studies. Seventeen hot spots 10 and 7 mm in diameter were placed in the breast region of a supine female phantom. Hot spot activity concentration was six times that of background. For the 49-pinhole camera and a reference, more conventional, broad field-of-view (FOV) SPECT system, projection data were computer simulated for 4-min scans and SPECT images were reconstructed. Hot-spot localization was evaluated using a nonprewhitening forced-choice numerical observer. Results: The CAD simulation studies found that robots could maneuver SPECT cameras about patients in position for radiation therapy. In the imaging studies, most hot spots were apparent in the 49-pinhole images. Average localization errors for 10-mm- and 7-mm-diameter hot spots were 0.4 and 1.7 mm, respectively, for the 49-pinhole system, and 3.1 and 5.7 mm, respectively, for the reference broad-FOV system. Conclusions: A robot could maneuver a multipinhole SPECT system about a patient in position for radiation therapy. The system could provide onboard functional and molecular imaging with 4-min scan times. PMID:24387490

Onboard functional and molecular imaging: A design investigation for robotic multipinhole SPECT

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bowsher, James, E-mail: james.bowsher@duke.edu; Giles, William; Yin, Fang-Fang

2014-01-15

Purpose: Onboard imaging—currently performed primarily by x-ray transmission modalities—is essential in modern radiation therapy. As radiation therapy moves toward personalized medicine, molecular imaging, which views individual gene expression, may also be important onboard. Nuclear medicine methods, such as single photon emission computed tomography (SPECT), are premier modalities for molecular imaging. The purpose of this study is to investigate a robotic multipinhole approach to onboard SPECT. Methods: Computer-aided design (CAD) studies were performed to assess the feasibility of maneuvering a robotic SPECT system about a patient in position for radiation therapy. In order to obtain fast, high-quality SPECT images, a 49-pinholemore » SPECT camera was designed which provides high sensitivity to photons emitted from an imaging region of interest. This multipinhole system was investigated by computer-simulation studies. Seventeen hot spots 10 and 7 mm in diameter were placed in the breast region of a supine female phantom. Hot spot activity concentration was six times that of background. For the 49-pinhole camera and a reference, more conventional, broad field-of-view (FOV) SPECT system, projection data were computer simulated for 4-min scans and SPECT images were reconstructed. Hot-spot localization was evaluated using a nonprewhitening forced-choice numerical observer. Results: The CAD simulation studies found that robots could maneuver SPECT cameras about patients in position for radiation therapy. In the imaging studies, most hot spots were apparent in the 49-pinhole images. Average localization errors for 10-mm- and 7-mm-diameter hot spots were 0.4 and 1.7 mm, respectively, for the 49-pinhole system, and 3.1 and 5.7 mm, respectively, for the reference broad-FOV system. Conclusions: A robot could maneuver a multipinhole SPECT system about a patient in position for radiation therapy. The system could provide onboard functional and molecular imaging with 4-min scan times.« less

Theragnostics for tumor and plaque angiogenesis with perfluorocarbon nanoemulsions

PubMed Central

Winter, P. M.; Caruthers, S. D.; Hughes, M. S.; Hu, Grace; Schmieder, A. H.; Wickline, S. A.

2011-01-01

Molecular imaging agents are extending the potential of noninvasive medical diagnosis from basic gross anatomical descriptions to complicated phenotypic characterizations based upon the recognition of unique cell-surface biochemical signatures. Although originally the purview of nuclear medicine, “molecular imaging” is now studied in conjunction with all clinically relevant imaging modalities. Of the myriad of particles that have emerged as prospective candidates for clinical translation, perfluorocarbon nanoparticles offer great potential for combining targeted imaging with drug delivery, much like the “magic bullet” envisioned by Paul Ehrlich 100 years ago. Perfluorocarbon nanoparticles, once studied in Phase III clinical trials as blood substitutes, have found new life for molecular imaging and drug delivery. The particles have been adapted for use with all clinically relevant modalities and for targeted drug delivery. In particular, their intravascular constraint due to particle size provides a distinct advantage for angiogenesis imaging and antiangiogenesis therapy. As perfluorocarbon nanoparticles have recently entered Phase I clinical study, this review provides a timely focus on the development of this platform technology and its application for angiogenesis-related pathologies. PMID:20411320

Photoacoustic and fluorescent imaging GAF2 photoswitchable chromoproteins (Conference Presentation)

NASA Astrophysics Data System (ADS)

Chee, Ryan K.; Li, Yan; Paproski, Robert J.; Campbell, Robert E.; Zemp, Roger J.

2017-03-01

Molecular photoacoustic imaging is hindered by hemoglobin background signal. Photoswitchable chromoproteins can be used to obtain images with significantly reduced background signal. Molecular imaging of multiple biological processes via multiple chromoprotiens is difficult due to overlapping imaging spectra. Using a new rate-of-change imaging methodology, we can obtain molecular images with multiple chromoprotiens with overlapping imaging spectra. We also present a new photoswitchable chromoprotein, GAF2, which is significantly smaller than the BphP1 which has shown promise for photoswitchable photoacoustic imaging [Yao et al., Nat. Meth. 13, 67-73 (2016)]. We use BphP1 and GAF2 with photoacoustic (Vevo LAZR, Fujifilm Visualsonics Inc) and fluorescence (In vivo Xtreme, Bruker) imaging systems to show background-free multiplexed images. We image before, after, and during photoconversion to obtain background-free rate-of-change images and compare our results to difference imaging and spectral demixing. After phantom imaging, we inject mice with different chromoprotein-expressing E. coli bacteria to show multiplexed images of bacterial infections. We show distinguishable differences in the rate-of-change between GAF2 and BphP1. We obtain rate-of-change feasibility images and in vivo images in mice showing the ability to differentiate between GAF2 and BphP1 even though they are spectrally similar. We photoconvert both GAF2 and BphP1 using 550nm and 735nm light. Phantom studies suggest a 10-20dB improvement in the rate-of-change and difference images in comparison to images with background. Multiplexed background-free molecular imaging using chromoproteins could prove to be a promising new imaging methodology especially when combined with spectral demixing.

Dual-tracer background subtraction approach for fluorescent molecular tomography

PubMed Central

Holt, Robert W.; El-Ghussein, Fadi; Davis, Scott C.; Samkoe, Kimberley S.; Gunn, Jason R.; Leblond, Frederic

2013-01-01

Abstract. Diffuse fluorescence tomography requires high contrast-to-background ratios to accurately reconstruct inclusions of interest. This is a problem when imaging the uptake of fluorescently labeled molecularly targeted tracers in tissue, which can result in high levels of heterogeneously distributed background uptake. We present a dual-tracer background subtraction approach, wherein signal from the uptake of an untargeted tracer is subtracted from targeted tracer signal prior to image reconstruction, resulting in maps of targeted tracer binding. The approach is demonstrated in simulations, a phantom study, and in a mouse glioma imaging study, demonstrating substantial improvement over conventional and homogenous background subtraction image reconstruction approaches. PMID:23292612

Molecular imaging using light-absorbing imaging agents and a clinical optical breast imaging system--a phantom study.

PubMed

van de Ven, Stephanie M W Y; Mincu, Niculae; Brunette, Jean; Ma, Guobin; Khayat, Mario; Ikeda, Debra M; Gambhir, Sanjiv S

2011-04-01

The aim of the study was to determine the feasibility of using a clinical optical breast scanner with molecular imaging strategies based on modulating light transmission. Different concentrations of single-walled carbon nanotubes (SWNT; 0.8-20.0 nM) and black hole quencher-3 (BHQ-3; 2.0-32.0 µM) were studied in specifically designed phantoms (200-1,570 mm(3)) with a clinical optical breast scanner using four wavelengths. Each phantom was placed in the scanner tank filled with optical matching medium. Background scans were compared to absorption scans, and reproducibility was assessed. All SWNT phantoms were detected at four wavelengths, with best results at 684 nm. Higher concentrations (≥8.0 µM) were needed for BHQ-3 detection, with the largest contrast at 684 nm. The optical absorption signal was dependent on phantom size and concentration. Reproducibility was excellent (intraclass correlation 0.93-0.98). Nanomolar concentrations of SWNT and micromolar concentrations of BHQ-3 in phantoms were reproducibly detected, showing the potential of light absorbers, with appropriate targeting ligands, as molecular imaging agents for clinical optical breast imaging.

Imaging patterns predict patient survival and molecular subtype in glioblastoma via machine learning techniques

PubMed Central

Macyszyn, Luke; Akbari, Hamed; Pisapia, Jared M.; Da, Xiao; Attiah, Mark; Pigrish, Vadim; Bi, Yingtao; Pal, Sharmistha; Davuluri, Ramana V.; Roccograndi, Laura; Dahmane, Nadia; Martinez-Lage, Maria; Biros, George; Wolf, Ronald L.; Bilello, Michel; O'Rourke, Donald M.; Davatzikos, Christos

2016-01-01

Background MRI characteristics of brain gliomas have been used to predict clinical outcome and molecular tumor characteristics. However, previously reported imaging biomarkers have not been sufficiently accurate or reproducible to enter routine clinical practice and often rely on relatively simple MRI measures. The current study leverages advanced image analysis and machine learning algorithms to identify complex and reproducible imaging patterns predictive of overall survival and molecular subtype in glioblastoma (GB). Methods One hundred five patients with GB were first used to extract approximately 60 diverse features from preoperative multiparametric MRIs. These imaging features were used by a machine learning algorithm to derive imaging predictors of patient survival and molecular subtype. Cross-validation ensured generalizability of these predictors to new patients. Subsequently, the predictors were evaluated in a prospective cohort of 29 new patients. Results Survival curves yielded a hazard ratio of 10.64 for predicted long versus short survivors. The overall, 3-way (long/medium/short survival) accuracy in the prospective cohort approached 80%. Classification of patients into the 4 molecular subtypes of GB achieved 76% accuracy. Conclusions By employing machine learning techniques, we were able to demonstrate that imaging patterns are highly predictive of patient survival. Additionally, we found that GB subtypes have distinctive imaging phenotypes. These results reveal that when imaging markers related to infiltration, cell density, microvascularity, and blood–brain barrier compromise are integrated via advanced pattern analysis methods, they form very accurate predictive biomarkers. These predictive markers used solely preoperative images, hence they can significantly augment diagnosis and treatment of GB patients. PMID:26188015

A Sensitive TLRH Targeted Imaging Technique for Ultrasonic Molecular Imaging

PubMed Central

Hu, Xiaowen; Zheng, Hairong; Kruse, Dustin E.; Sutcliffe, Patrick; Stephens, Douglas N.; Ferrara, Katherine W.

2010-01-01

The primary goals of ultrasound molecular imaging are the detection and imaging of ultrasound contrast agents (microbubbles), which are bound to specific vascular surface receptors. Imaging methods that can sensitively and selectively detect and distinguish bound microbubbles from freely circulating microbubbles (free microbubbles) and surrounding tissue are critically important for the practical application of ultrasound contrast molecular imaging. Microbubbles excited by low frequency acoustic pulses emit wide-band echoes with a bandwidth extending beyond 20 MHz; we refer to this technique as TLRH (transmission at a low frequency and reception at a high frequency). Using this wideband, transient echo, we have developed and implemented a targeted imaging technique incorporating a multi-frequency co-linear array and the Siemens Antares® imaging system. The multi-frequency co-linear array integrates a center 5.4 MHz array, used to receive echoes and produce radiation force, and two outer 1.5 MHz arrays used to transmit low frequency incident pulses. The targeted imaging technique makes use of an acoustic radiation force sub-sequence to enhance accumulation and a TLRH imaging sub-sequence to detect bound microbubbles. The radiofrequency (RF) data obtained from the TLRH imaging sub-sequence are processsed to separate echo signatures between tissue, free microbubbles, and bound microbubbles. By imaging biotin-coated microbubbles targeted to avidin-coated cellulose tubes, we demonstrate that the proposed method has a high contrast-to-tissue ratio (up to 34 dB) and a high sensitivity to bound microbubbles (with the ratio of echoes from bound microbubbles versus free microbubbles extending up to 23 dB). The effects of the imaging pulse acoustic pressure, the radiation force sub-sequence and the use of various slow-time filters on the targeted imaging quality are studied. The TLRH targeted imaging method is demonstrated in this study to provide sensitive and selective detection of bound microbubbles for ultrasound molecularly-targeted imaging. PMID:20178897

Molecular Imaging of Vasa Vasorum Neovascularization via DEspR-targeted Contrast-enhanced Ultrasound Micro-imaging in Transgenic Atherosclerosis Rat Model

PubMed Central

Decano, Julius L.; Moran, Anne Marie; Ruiz-Opazo, Nelson; Herrera, Victoria L. M.

2011-01-01

Purpose Given that carotid vasa vasorum neovascularization is associated with increased risk for stroke and cardiac events, the present in vivo study was designed to investigate molecular imaging of carotid artery vasa vasorum neovascularization via target-specific contrast-enhanced ultrasound (CEU) micro-imaging. Procedures Molecular imaging was performed in male transgenic rats with carotid artery disease and non-transgenic controls using dual endothelin1/VEGFsp receptor (DEspR)-targeted microbubbles (MBD) and the Vevo770 micro-imaging system and CEU imaging software. Results DEspR-targeted CEU-positive imaging exhibited significantly higher contrast intensity signal (CIS)-levels and pre-/post-destruction CIS-differences in seven of 13 transgenic rats, in contrast to significantly lower CIS-levels and differences in control isotype-targeted microbubble (MBC)-CEU imaging (n =8) and in MBD CEU-imaging of five non-transgenic control rats (P<0.0001). Ex vivo immunofluorescence analysis demonstrated binding of MBD to DEspR-positive endothelial cells; and association of DEspR-targeted increased contrast intensity signals with DEspR expression in vasa vasorum neovessel and intimal lesions. In vitro analysis demonstrated dose-dependent binding of MBD to DEspR-positive human endothelial cells with increasing %cells bound and number of MBD per cell, in contrast to MBC or non-labeled microbubbles (P<0.0001). Conclusion In vivo DEspR-targeted molecular imaging detected increased DEspR-expression in carotid artery lesions and in expanded vasa vasorum neovessels in transgenic rats with carotid artery disease. Future studies are needed to determine predictive value for stroke or heart disease in this transgenic atherosclerosis rat model and translational applications. PMID:20972637

Noninvasive Assessment of Cell Fate and Biology in Transplanted Mesenchymal Stem Cells.

PubMed

Franchi, Federico; Rodriguez-Porcel, Martin

2017-01-01

Recently, molecular imaging has become a conditio sine qua non for cell-based regenerative medicine. Developments in molecular imaging techniques, such as reporter gene technology, have increasingly enabled the noninvasive assessment of the fate and biology of cells after cardiovascular applications. In this context, bioluminescence imaging is the most commonly used imaging modality in small animal models of preclinical studies. Here, we present a detailed protocol of a reporter gene imaging approach for monitoring the viability and biology of Mesenchymal Stem Cells transplanted in a mouse model of myocardial ischemia reperfusion injury.

[Molecular imaging; current status and future prospects in USA].

PubMed

Kobayashi, Hisataka

2007-02-01

The goal of this review is to introduce the definition, current status, and future prospects of the molecular imaging, which has recently been a hot topic in medicine and the biological science in USA. In vivo imaging methods to visualize the molecular events and functions in organs or animals/humans are overviewed and discussed especially in combinations of imaging modalities (machines) and contrast agents(chemicals) used in the molecular imaging. Next, the close relationship between the molecular imaging and the nanotechnology, an important part of nanomedicine, is stressed from the aspect of united multidisciplinary sciences such as physics, chemistry, biology, and medicine.

Special conference of the American Association for Cancer Research on molecular imaging in cancer: linking biology, function, and clinical applications in vivo.

PubMed

Luker, Gary D

2002-04-01

The AACR Special Conference on Molecular Imaging in Cancer: Linking Biology, Function, and Clinical Applications In Vivo, was held January 23-27, 2002, at the Contemporary Hotel, Walt Disney World, Orlando, FL. Co-Chairs David Piwnica-Worms, Patricia Price and Thomas Meade brought together researchers with diverse expertise in molecular biology, gene therapy, chemistry, engineering, pharmacology, and imaging to accelerate progress in developing and applying technologies for imaging specific cellular and molecular signals in living animals and humans. The format of the conference was the presentation of research that focused on basic and translational biology of cancer and current state-of-the-art techniques for molecular imaging in animal models and humans. This report summarizes the special conference on molecular imaging, highlighting the interfaces of molecular biology with animal models, instrumentation, chemistry, and pharmacology that are essential to convert the dreams and promise of molecular imaging into improved understanding, diagnosis, and management of cancer.

Interventional Molecular Imaging.

PubMed

Solomon, Stephen B; Cornelis, Francois

2016-04-01

Although molecular imaging has had a dramatic impact on diagnostic imaging, it has only recently begun to be integrated into interventional procedures. Its significant impact is attributed to its ability to provide noninvasive, physiologic information that supplements conventional morphologic imaging. The four major interventional opportunities for molecular imaging are, first, to provide guidance to localize a target; second, to provide tissue analysis to confirm that the target has been reached; third, to provide in-room, posttherapy assessment; and fourth, to deliver targeted therapeutics. With improved understanding and application of(18)F-FDG, as well as the addition of new molecular probes beyond(18)F-FDG, the future holds significant promise for the expansion of molecular imaging into the realm of interventional procedures. © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Study on photon transport problem based on the platform of molecular optical simulation environment.

PubMed

Peng, Kuan; Gao, Xinbo; Liang, Jimin; Qu, Xiaochao; Ren, Nunu; Chen, Xueli; Ma, Bin; Tian, Jie

2010-01-01

As an important molecular imaging modality, optical imaging has attracted increasing attention in the recent years. Since the physical experiment is usually complicated and expensive, research methods based on simulation platforms have obtained extensive attention. We developed a simulation platform named Molecular Optical Simulation Environment (MOSE) to simulate photon transport in both biological tissues and free space for optical imaging based on noncontact measurement. In this platform, Monte Carlo (MC) method and the hybrid radiosity-radiance theorem are used to simulate photon transport in biological tissues and free space, respectively, so both contact and noncontact measurement modes of optical imaging can be simulated properly. In addition, a parallelization strategy for MC method is employed to improve the computational efficiency. In this paper, we study the photon transport problems in both biological tissues and free space using MOSE. The results are compared with Tracepro, simplified spherical harmonics method (SP(n)), and physical measurement to verify the performance of our study method on both accuracy and efficiency.

Study on Photon Transport Problem Based on the Platform of Molecular Optical Simulation Environment

PubMed Central

Peng, Kuan; Gao, Xinbo; Liang, Jimin; Qu, Xiaochao; Ren, Nunu; Chen, Xueli; Ma, Bin; Tian, Jie

2010-01-01

As an important molecular imaging modality, optical imaging has attracted increasing attention in the recent years. Since the physical experiment is usually complicated and expensive, research methods based on simulation platforms have obtained extensive attention. We developed a simulation platform named Molecular Optical Simulation Environment (MOSE) to simulate photon transport in both biological tissues and free space for optical imaging based on noncontact measurement. In this platform, Monte Carlo (MC) method and the hybrid radiosity-radiance theorem are used to simulate photon transport in biological tissues and free space, respectively, so both contact and noncontact measurement modes of optical imaging can be simulated properly. In addition, a parallelization strategy for MC method is employed to improve the computational efficiency. In this paper, we study the photon transport problems in both biological tissues and free space using MOSE. The results are compared with Tracepro, simplified spherical harmonics method (S P n), and physical measurement to verify the performance of our study method on both accuracy and efficiency. PMID:20445737

Genomics, proteomics, MEMS and SAIF: which role for diagnostic imaging?

PubMed

Grassi, R; Lagalla, R; Rotondo, A

2008-09-01

In these three words--genomics, proteomics and nanotechnologies--is the future of medicine of the third millennium, which will be characterised by more careful attention to disease prevention, diagnosis and treatment. Molecular imaging appears to satisfy this requirement. It is emerging as a new science that brings together molecular biology and in vivo imaging and represents the key for the application of personalized medicine. Micro-PET (positron emission tomography), micro-SPECT (single photon emission computed tomography), micro-CT (computed tomography), micro-MR (magnetic resonance), micro-US (ultrasound) and optical imaging are all molecular imaging techniques, several of which are applied only in preclinical settings on animal models. Others, however, are applied routinely in both clinical and preclinical setting. Research on small animals allows investigation of the genesis and development of diseases, as well as drug efficacy and the development of personalized therapies, through the study of biological processes that precede the expression of common symptoms of a pathology. Advances in molecular imaging were made possible only by collaboration among scientists in the fields of radiology, chemistry, molecular and cell biology, physics, mathematics, pharmacology, gene therapy and oncology. Although until now researchers have traditionally limited their interactions, it is only by increasing these connections that the current gaps in terminology, methods and approaches that inhibit scientific progress can be eliminated.

Combination of cross-sectional and molecular imaging studies in the localization of gastroenteropancreatic neuroendocrine tumors.

PubMed

Toumpanakis, Christos; Kim, Michelle K; Rinke, Anja; Bergestuen, Deidi S; Thirlwell, Christina; Khan, Mohid S; Salazar, Ramon; Oberg, Kjell

2014-01-01

Molecular imaging modalities exploit aspects of neuroendocrine tumors (NET) pathophysiology for both diagnostic imaging and therapeutic purposes. The characteristic metabolic pathways of NET determine which tracers are useful for their visualization. In this review, we summarize the diagnostic value of all available molecular imaging studies, present data about their use in daily practice in NET centers globally, and finally make recommendations about the appropriate use of those modalities in specific clinical scenarios. Somatostatin receptor scintigraphy (SRS) continues to have a central role in the diagnostic workup of patients with NET, as it is also widely available. However, and despite the lack of prospective randomized studies, many NET experts predict that Gallium-68 ((68)Ga)-DOTA positron emission tomography (PET) techniques may replace SRS in the future, not only because of their technical advantages, but also because they are superior in patients with small-volume disease, in patients with skeletal metastases, and in those with occult primary tumors. Carbon-11 ((11)C)-5-hydroxy-L-tryptophan (5-HTP) PET and (18)F-dihydroxyphenylalanine ((18)F-DOPA) PET are new molecular imaging techniques of limited availability, and based on retrospective data, their sensitivities seem to be inferior to that of (68)Ga-DOTA PET. Glucagon-like-peptide-1 (GLP-1) receptor imaging seems promising for localization of the primary in benign insulinomas, but is currently available only in a few centers. Fluorine-18 ((18)F)-fluorodeoxyglucose ((18)F-FDG) PET was initially thought to be of limited value in NET, due to their usually slow-growing nature. However, according to subsequent data, (18)F-FDG PET is particularly helpful for visualizing the more aggressive NET, such as poorly differentiated neuroendocrine carcinomas, and well-differentiated tumors with Ki67 values >10%. According to limited data, (18)F-FDG-avid tumor lesions, even in slow-growing NET, may indicate a more aggressive disease course. When a secondary malignancy has already been established or is strongly suspected, combining molecular imaging techniques (e.g. (18)F-FDG PET and (68)Ga-DOTA PET) takes advantage of the diverse avidities of different tumor types to differentiate lesions of different origins. All the above-mentioned molecular imaging studies should always be reviewed and interpreted in a multidisciplinary (tumor board) meeting in combination with the conventional cross-sectional imaging, as the latter remains the imaging of choice for the evaluation of treatment response and disease follow-up. © 2014 S. Karger AG, Basel

SU-E-I-39: Molecular Image Guided Cancer Stem Cells Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Abdollahi, H

Purpose: Cancer stem cells resistance to radiation is a problematic issue that has caused a big fail in cancer treatment. Methods: As a primary work, molecular imaging can indicate the main mechanisms of radiation resistance of cancer stem cells. By developing and commissioning new probes and nanomolecules and biomarkers, radiation scientist will able to identify the essential pathways of radiation resistance of cancer stem cells. As the second solution, molecular imaging is a best way to find biological target volume and delineate cancer stem cell tissues. In the other hand, by molecular imaging techniques one can image the treatment responsemore » in tumor and also in normal tissue. In this issue, the response of cancer stem cells to radiation during therapy course can be imaged, also the main mechanisms of radiation resistance and finding the best radiation modifiers (sensitizers) can be achieved by molecular imaging modalities. In adaptive radiotherapy the molecular imaging plays a vital role to have higher tumor control probability by delivering high radiation doses to cancer stem cells in any time of treatment. The outcome of a feasible treatment is dependent to high cancer stem cells response to radiation and removing all of which, so a good imaging modality can show this issue and preventing of tumor recurrence and metastasis. Results: Our results are dependent to use of molecular imaging as a new modality in the clinic. We propose molecular imaging as a new radiobiological technique to solve radiation therapy problems due to cancer stem cells. Conclusion: Molecular imaging guided cancer stem cell diagnosis and therapy is a new approach in the field of cancer treatment. This new radiobiological imaging technique should be developed in all clinics as a feasible tool that is more biological than physical imaging.« less

Recent development of nanoparticles for molecular imaging

NASA Astrophysics Data System (ADS)

Kim, Jonghoon; Lee, Nohyun; Hyeon, Taeghwan

2017-10-01

Molecular imaging enables us to non-invasively visualize cellular functions and biological processes in living subjects, allowing accurate diagnosis of diseases at early stages. For successful molecular imaging, a suitable contrast agent with high sensitivity is required. To date, various nanoparticles have been developed as contrast agents for medical imaging modalities. In comparison with conventional probes, nanoparticles offer several advantages, including controllable physical properties, facile surface modification and long circulation time. In addition, they can be integrated with various combinations for multimodal imaging and therapy. In this opinion piece, we highlight recent advances and future perspectives of nanomaterials for molecular imaging. This article is part of the themed issue 'Challenges for chemistry in molecular imaging'.

Magnetically engineered smart thin films: toward lab-on-chip ultra-sensitive molecular imaging.

PubMed

Hassan, Muhammad A; Saqib, Mudassara; Shaikh, Haseeb; Ahmad, Nasir M; Elaissari, Abdelhamid

2013-03-01

Magnetically responsive engineered smart thin films of nanoferrites as contrast agent are employed to develop surface based magnetic resonance imaging to acquire simple yet fast molecular imaging. The work presented here can be of significant potential for future lab-on-chip point-of-care diagnostics from the whole blood pool on almost any substrates to reduce or even prevent clinical studies involve a living organism to enhance the non-invasive imaging to advance the '3Rs' of work in animals-replacement, refinement and reduction.

Emergence of molecular imaging of aortic aneurysm; implications for risk stratification and management

PubMed Central

Golestani, Reza; Sadeghi, Mehran M.

2014-01-01

Summary Imaging cellular and molecular processes associated with aneurysm expansion, dissection, and rupture can potentially transform the management of patients with thoracic and abdominal aortic aneurysm (TAA and AAA). Here, we review recent advances in molecular imaging of aortic aneurysm, focusing on imaging modalities with the greatest potential for clinical translation and application, PET, SPECT and MRI. Inflammation (e.g., with 18F-FDG, nanoparticles) and matrix remodeling (e.g., with matrix metalloproteinase-targeted tracers) are highlighted as promising targets for molecular imaging of aneurysm. Potential alternative or complementary approaches to molecular imaging for aneurysm risk stratification are briefly discussed. PMID:24381115

Intravital imaging of mouse colonic adenoma using MMP-based molecular probes with multi-channel fluorescence endoscopy.

PubMed

Oh, Gyungseok; Yoo, Su Woong; Jung, Yebin; Ryu, Yeon-Mi; Park, Youngrong; Kim, Sang-Yeob; Kim, Ki Hean; Kim, Sungjee; Myung, Seung-Jae; Chung, Euiheon

2014-05-01

Intravital imaging has provided molecular, cellular and anatomical insight into the study of tumor. Early detection and treatment of gastrointestinal (GI) diseases can be enhanced with specific molecular markers and endoscopic imaging modalities. We present a wide-field multi-channel fluorescence endoscope to screen GI tract for colon cancer using multiple molecular probes targeting matrix metalloproteinases (MMP) conjugated with quantum dots (QD) in AOM/DSS mouse model. MMP9 and MMP14 antibody (Ab)-QD conjugates demonstrate specific binding to colonic adenoma. The average target-to-background (T/B) ratios are 2.10 ± 0.28 and 1.78 ± 0.18 for MMP14 Ab-QD and MMP9 Ab-QD, respectively. The overlap between the two molecular probes is 67.7 ± 8.4%. The presence of false negative indicates that even more number of targeting could increase the sensitivity of overall detection given heterogeneous molecular expression in tumors. Our approach indicates potential for the screening of small or flat lesions that are precancerous.

Molecular imaging needles: dual-modality optical coherence tomography and fluorescence imaging of labeled antibodies deep in tissue

PubMed Central

Scolaro, Loretta; Lorenser, Dirk; Madore, Wendy-Julie; Kirk, Rodney W.; Kramer, Anne S.; Yeoh, George C.; Godbout, Nicolas; Sampson, David D.; Boudoux, Caroline; McLaughlin, Robert A.

2015-01-01

Molecular imaging using optical techniques provides insight into disease at the cellular level. In this paper, we report on a novel dual-modality probe capable of performing molecular imaging by combining simultaneous three-dimensional optical coherence tomography (OCT) and two-dimensional fluorescence imaging in a hypodermic needle. The probe, referred to as a molecular imaging (MI) needle, may be inserted tens of millimeters into tissue. The MI needle utilizes double-clad fiber to carry both imaging modalities, and is interfaced to a 1310-nm OCT system and a fluorescence imaging subsystem using an asymmetrical double-clad fiber coupler customized to achieve high fluorescence collection efficiency. We present, to the best of our knowledge, the first dual-modality OCT and fluorescence needle probe with sufficient sensitivity to image fluorescently labeled antibodies. Such probes enable high-resolution molecular imaging deep within tissue. PMID:26137379

Ultra-low-dose Ultrasound Molecular Imaging for the Detection of Angiogenesis in a Mouse Murine Tumor Model: How Little Can We See?

PubMed Central

Wang, Shiying; Herbst, Elizabeth B.; Mauldin, F. William; Diakova, Galina B.; Klibanov, Alexander L.; Hossack, John A.

2016-01-01

Objectives The objective of this study is to evaluate the minimum microbubble dose for ultrasound molecular imaging to achieve statistically significant detection of angiogenesis in a mouse model. Materials and Methods The pre-burst minus post-burst method was implemented on a Verasonics ultrasound research scanner using a multi-frame compounding pulse inversion imaging sequence. Biotinylated lipid (distearoyl phosphatidylcholine, DSPC-based) microbubbles that were conjugated with anti-vascular endothelial growth factor 2 (VEGFR2) antibody (MBVEGFR2) or isotype control antibody (MBControl) were injected into mice carrying adenocarcinoma xenografts. Different injection doses ranging from 5 × 104 to 1 × 107 microbubbles per mouse were evaluated to determine the minimum diagnostically effective dose. Results The proposed imaging sequence was able to achieve statistically significant detection (p < 0.05, n = 5) of VEGFR2 in tumors with a minimum MBVEGFR2 injection dose of only 5 × 104 microbubbles per mouse (DSPC at 0.053 ng/g mouse body mass). Non-specific adhesion of MBControl at the same injection dose was negligible. Additionally, the targeted contrast ultrasound signal of MBVEGFR2 decreased with lower microbubble doses, while non-specific adhesion of MBControl increased with higher microbubble doses. Conclusions 5 × 104 microbubbles per animal is now the lowest injection dose on record for ultrasound molecular imaging to achieve statistically significant detection of molecular targets in vivo. Findings in this study provide us with further guidance for future developments of clinically translatable ultrasound molecular imaging applications using a lower dose of microbubbles. PMID:27654582

Fluorescent imaging of cancerous tissues for targeted surgery

PubMed Central

Bu, Lihong; Shen, Baozhong; Cheng, Zhen

2014-01-01

To maximize tumor excision and minimize collateral damage is the primary goal of cancer surgery. Emerging molecular imaging techniques have to “image-guided surgery” developing into “molecular imaging-guided surgery”, which is termed “targeted surgery” in this review. Consequently, the precision of surgery can be advanced from tissue-scale to molecule-scale, enabling “targeted surgery” to be a component of “targeted therapy”. Evidence from numerous experimental and clinical studies has demonstrated significant benefits of fluorescent imaging in targeted surgery with preoperative molecular diagnostic screening. Fluorescent imaging can help to improve intraoperative staging and enable more radical cytoreduction, detect obscure tumor lesions in special organs, highlight tumor margins, better map lymph node metastases, and identify important normal structures intraoperatively. Though limited tissue penetration of fluorescent imaging and tumor heterogeneity are two major hurdles for current targeted surgery, multimodality imaging and multiplex imaging may provide potential solutions to overcome these issues, respectively. Moreover, though many fluorescent imaging techniques and probes have been investigated, targeted surgery remains at a proof-of-principle stage. The impact of fluorescent imaging on cancer surgery will likely be realized through persistent interdisciplinary amalgamation of research in diverse fields. PMID:25064553

Imaging Live Drosophila Brain with Two-Photon Fluorescence Microscopy

NASA Astrophysics Data System (ADS)

Ahmed, Syeed Ehsan

Two-photon fluorescence microscopy is an imaging technique which delivers distinct benefits for in vivo cellular and molecular imaging. Cyclic adenosine monophosphate (cAMP), a second messenger molecule, is responsible for triggering many physiological changes in neural system. However, the mechanism by which this molecule regulates responses in neuron cells is not yet clearly understood. When cAMP binds to a target protein, it changes the structure of that protein. Therefore, studying this molecular structure change with fluorescence resonance energy transfer (FRET) imaging can shed light on the cAMP functioning mechanism. FRET is a non-radiative dipole-dipole coupling which is sensitive to small distance change in nanometer scale. In this study we have investigated the effect of dopamine in cAMP dynamics in vivo. In our study two-photon fluorescence microscope was used for imaging mushroom bodies inside live Drosophila melanogaster brain and we developed a method for studying the change in cyclic AMP level.

Optical/MRI Multimodality Molecular Imaging

NASA Astrophysics Data System (ADS)

Ma, Lixin; Smith, Charles; Yu, Ping

2007-03-01

Multimodality molecular imaging that combines anatomical and functional information has shown promise in development of tumor-targeted pharmaceuticals for cancer detection or therapy. We present a new multimodality imaging technique that combines fluorescence molecular tomography (FMT) and magnetic resonance imaging (MRI) for in vivo molecular imaging of preclinical tumor models. Unlike other optical/MRI systems, the new molecular imaging system uses parallel phase acquisition based on heterodyne principle. The system has a higher accuracy of phase measurements, reduced noise bandwidth, and an efficient modulation of the fluorescence diffuse density waves. Fluorescent Bombesin probes were developed for targeting breast cancer cells and prostate cancer cells. Tissue phantom and small animal experiments were performed for calibration of the imaging system and validation of the targeting probes.

Folic acid-functionalized up-conversion nanoparticles: toxicity studies in vivo and in vitro and targeted imaging applications

NASA Astrophysics Data System (ADS)

Sun, Lining; Wei, Zuwu; Chen, Haige; Liu, Jinliang; Guo, Jianjian; Cao, Ming; Wen, Tieqiao; Shi, Liyi

2014-07-01

Folate receptors (FRs) are overexpressed on a variety of human cancer cells and tissues, including cancers of the breast, ovaries, endometrium, and brain. This over-expression of FRs can be used to target folate-linked imaging specifically to FR-expressing tumors. Fluorescence is emerging as a powerful new modality for molecular imaging in both the diagnosis and treatment of disease. Combining innovative molecular biology and chemistry, we prepared three kinds of folate-targeted up-conversion nanoparticles as imaging agents (UCNC-FA: UCNC-Er-FA, UCNC-Tm-FA, and UCNC-Er,Tm-FA). In vivo and in vitro toxicity studies showed that these nanoparticles have both good biocompatibility and low toxicity. Moreover, the up-conversion luminescence imaging indicated that they have good targeting to HeLa cells and can therefore serve as potential fluorescent contrast agents.Folate receptors (FRs) are overexpressed on a variety of human cancer cells and tissues, including cancers of the breast, ovaries, endometrium, and brain. This over-expression of FRs can be used to target folate-linked imaging specifically to FR-expressing tumors. Fluorescence is emerging as a powerful new modality for molecular imaging in both the diagnosis and treatment of disease. Combining innovative molecular biology and chemistry, we prepared three kinds of folate-targeted up-conversion nanoparticles as imaging agents (UCNC-FA: UCNC-Er-FA, UCNC-Tm-FA, and UCNC-Er,Tm-FA). In vivo and in vitro toxicity studies showed that these nanoparticles have both good biocompatibility and low toxicity. Moreover, the up-conversion luminescence imaging indicated that they have good targeting to HeLa cells and can therefore serve as potential fluorescent contrast agents. Electronic supplementary information (ESI) available: Up-conversion luminescence spectra of UCNC-Er and UCNC-Er-FA, UCNC-Tm and UCNC-Tm-FA. Confocal luminescence imaging data collected as a series along the Z optical axis. See DOI: 10.1039/c4nr02312a

Imaging features of breast cancers on digital breast tomosynthesis according to molecular subtype: association with breast cancer detection.

PubMed

Lee, Su Hyun; Chang, Jung Min; Shin, Sung Ui; Chu, A Jung; Yi, Ann; Cho, Nariya; Moon, Woo Kyung

2017-12-01

To evaluate imaging features of breast cancers on digital breast tomosynthesis (DBT) according to molecular subtype and to determine whether the molecular subtype affects breast cancer detection on DBT. This was an institutional review board--approved study with a waiver of informed consent. DBT findings of 288 invasive breast cancers were reviewed according to Breast Imaging Reporting and Data System lexicon. Detectability of breast cancer was quantified by the number of readers (0-3) who correctly detected the cancer in an independent blinded review. DBT features and the cancer detectability score according to molecular subtype were compared using Fisher's exact test and analysis of variance. Of 288 invasive cancers, 194 were hormone receptor (HR)-positive, 48 were human epidermal growth factor receptor 2 (HER2) positive and 46 were triple negative breast cancers. The most common DBT findings were irregular spiculated masses for HR-positive cancer, fine pleomorphic or linear branching calcifications for HER2 positive cancer and irregular masses with circumscribed margins for triple negative breast cancers (p < 0.001). Cancer detectability on DBT was not significantly different according to molecular subtype (p = 0.213) but rather affected by tumour size, breast density and presence of mass or calcifications. Breast cancers showed different imaging features according to molecular subtype; however, it did not affect the cancer detectability on DBT. Advances in knowledge: DBT showed characteristic imaging features of breast cancers according to molecular subtype. However, cancer detectability on DBT was not affected by molecular subtype of breast cancers.

Imaging patterns predict patient survival and molecular subtype in glioblastoma via machine learning techniques.

PubMed

Macyszyn, Luke; Akbari, Hamed; Pisapia, Jared M; Da, Xiao; Attiah, Mark; Pigrish, Vadim; Bi, Yingtao; Pal, Sharmistha; Davuluri, Ramana V; Roccograndi, Laura; Dahmane, Nadia; Martinez-Lage, Maria; Biros, George; Wolf, Ronald L; Bilello, Michel; O'Rourke, Donald M; Davatzikos, Christos

2016-03-01

MRI characteristics of brain gliomas have been used to predict clinical outcome and molecular tumor characteristics. However, previously reported imaging biomarkers have not been sufficiently accurate or reproducible to enter routine clinical practice and often rely on relatively simple MRI measures. The current study leverages advanced image analysis and machine learning algorithms to identify complex and reproducible imaging patterns predictive of overall survival and molecular subtype in glioblastoma (GB). One hundred five patients with GB were first used to extract approximately 60 diverse features from preoperative multiparametric MRIs. These imaging features were used by a machine learning algorithm to derive imaging predictors of patient survival and molecular subtype. Cross-validation ensured generalizability of these predictors to new patients. Subsequently, the predictors were evaluated in a prospective cohort of 29 new patients. Survival curves yielded a hazard ratio of 10.64 for predicted long versus short survivors. The overall, 3-way (long/medium/short survival) accuracy in the prospective cohort approached 80%. Classification of patients into the 4 molecular subtypes of GB achieved 76% accuracy. By employing machine learning techniques, we were able to demonstrate that imaging patterns are highly predictive of patient survival. Additionally, we found that GB subtypes have distinctive imaging phenotypes. These results reveal that when imaging markers related to infiltration, cell density, microvascularity, and blood-brain barrier compromise are integrated via advanced pattern analysis methods, they form very accurate predictive biomarkers. These predictive markers used solely preoperative images, hence they can significantly augment diagnosis and treatment of GB patients. © The Author(s) 2015. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Light microscopy applications in systems biology: opportunities and challenges

PubMed Central

2013-01-01

Biological systems present multiple scales of complexity, ranging from molecules to entire populations. Light microscopy is one of the least invasive techniques used to access information from various biological scales in living cells. The combination of molecular biology and imaging provides a bottom-up tool for direct insight into how molecular processes work on a cellular scale. However, imaging can also be used as a top-down approach to study the behavior of a system without detailed prior knowledge about its underlying molecular mechanisms. In this review, we highlight the recent developments on microscopy-based systems analyses and discuss the complementary opportunities and different challenges with high-content screening and high-throughput imaging. Furthermore, we provide a comprehensive overview of the available platforms that can be used for image analysis, which enable community-driven efforts in the development of image-based systems biology. PMID:23578051

A review of performance of near-infrared fluorescence imaging devices used in clinical studies

PubMed Central

Zhu, B

2015-01-01

Near-infrared fluorescence (NIRF) molecular imaging holds great promise as a new “point-of-care” medical imaging modality that can potentially provide the sensitivity of nuclear medicine techniques, but without the radioactivity that can otherwise place limitations of usage. Recently, NIRF imaging devices of a variety of designs have emerged in the market and in investigational clinical studies using indocyanine green (ICG) as a non-targeting NIRF contrast agent to demark the blood and lymphatic vasculatures both non-invasively and intraoperatively. Approved in the USA since 1956 for intravenous administration, ICG has been more recently used off label in intradermal or subcutaneous administrations for fluorescence imaging of the lymphatic vasculature and lymph nodes. Herein, we summarize the devices of a variety of designs, summarize their performance in lymphatic imaging in a tabular format and comment on necessary efforts to develop standards for device performance to compare and use these emerging devices in future, NIRF molecular imaging studies. PMID:25410320

Molecular imaging with bioconjugates in mouse models of cancer.

PubMed

Mather, Stephen

2009-04-01

The definition of molecular imaging provided by the Society of Nuclear Medicine is "the visualization, characterization and measurement of biological processes at the molecular and cellular levels in humans and other living systems". This review gives an overview of the technologies available for and the potential benefits from molecular imaging at the preclinical stage. It focuses on the use of imaging probes based on bioconjugates and for reasons of brevity confines itself to discussion of applications in the field of oncology, although molecular imaging can be equally useful in many fields including cardiovascular medicine, neurosciences, infection, and others.

Simultaneous in vivo imaging of melanin and lipofuscin in the retina with photoacoustic ophthalmoscopy and autofluorescence imaging.

PubMed

Zhang, Xiangyang; Zhang, Hao F; Puliafito, Carmen A; Jiao, Shuliang

2011-08-01

We combined photoacoustic ophthalmoscopy (PAOM) with autofluorescence imaging for simultaneous in vivo imaging of dual molecular contrasts in the retina using a single light source. The dual molecular contrasts come from melanin and lipofuscin in the retinal pigment epithelium (RPE). Melanin and lipofuscin are two types of pigments and are believed to play opposite roles (protective versus exacerbate) in the RPE in the aging process. We have successfully imaged the retina of pigmented and albino rats at different ages. The experimental results showed that multimodal PAOM system can be a potentially powerful tool in the study of age-related degenerative retinal diseases.

Simultaneous in vivo imaging of melanin and lipofuscin in the retina with photoacoustic ophthalmoscopy and autofluorescence imaging

NASA Astrophysics Data System (ADS)

Zhang, Xiangyang; Zhang, Hao F.; Puliafito, Carmen A.; Jiao, Shuliang

2011-08-01

We combined photoacoustic ophthalmoscopy (PAOM) with autofluorescence imaging for simultaneous in vivo imaging of dual molecular contrasts in the retina using a single light source. The dual molecular contrasts come from melanin and lipofuscin in the retinal pigment epithelium (RPE). Melanin and lipofuscin are two types of pigments and are believed to play opposite roles (protective versus exacerbate) in the RPE in the aging process. We have successfully imaged the retina of pigmented and albino rats at different ages. The experimental results showed that multimodal PAOM system can be a potentially powerful tool in the study of age-related degenerative retinal diseases.

Role of topographical defects in organic film growth of 4,4' -biphenyldicarboxylic acid on graphene: A low-energy electron microscopy study

NASA Astrophysics Data System (ADS)

Khokhar, Fawad S.; van Gastel, Raoul; Poelsema, Bene

2010-11-01

We have used low-energy electron microscopy (LEEM) to study the formation of self-assembled molecular networks on graphene sheets. 4,4' -biphenyldicarboxylic acid (BDA) molecular networks were grown using organic molecular beam epitaxy. LEEM images provide direct insight in the growth dynamics and show that defects in the graphene play a crucial role in the final morphology of the molecular film that forms. BDA is demonstrated to form hydrogen bond-stabilized chains on graphene. Dark-field LEEM images reveal that the same defects that determine the morphology of the film, also direct the orientation of the domains, highlighting the importance of understanding the role of defects in epitaxial processes on graphene.

Proteomics in Diagnostic Pathology

PubMed Central

Chaurand, Pierre; Sanders, Melinda E.; Jensen, Roy A.; Caprioli, Richard M.

2004-01-01

Direct tissue profiling and imaging mass spectrometry (MS) provide a molecular assessment of numerous expressed proteins within a tissue sample. MALDI MS (matrix-assisted laser desorption ionization) analysis of thin tissue sections results in the visualization of 500 to 1000 individual protein signals in the molecular weight range from 2000 to over 200,000. These signals directly correlate with protein distribution within a specific region of the tissue sample. The systematic investigation of the section allows the construction of ion density maps, or specific molecular images, for virtually every signal detected in the analysis. Ultimately, hundreds of images, each at a specific molecular weight, may be obtained. To date, profiling and imaging MS has been applied to multiple diseased tissues, including human non-small cell lung tumors, gliomas, and breast tumors. Interrogation of the resulting complex MS data sets using modern biocomputational tools has resulted in identification of both disease-state and patient-prognosis specific protein patterns. These studies suggest that such proteomic information will become more and more important in assessing disease progression, prognosis, and drug efficacy. Molecular histology has been known for some time and its value clear in the field of pathology. Imaging mass spectrometry brings a new dimension of molecular data, one focusing on the disease phenotype. The present article reviews the state of the art of the technology and its complementarity with traditional histopathological analyses. PMID:15466373

Precise diagnosis in different scenarios using photoacoustic and fluorescence imaging with dual-modality nanoparticles

NASA Astrophysics Data System (ADS)

Peng, Dong; Du, Yang; Shi, Yiwen; Mao, Duo; Jia, Xiaohua; Li, Hui; Zhu, Yukun; Wang, Kun; Tian, Jie

2016-07-01

Photoacoustic imaging and fluorescence molecular imaging are emerging as important research tools for biomedical studies. Photoacoustic imaging offers both strong optical absorption contrast and high ultrasonic resolution, and fluorescence molecular imaging provides excellent superficial resolution, high sensitivity, high throughput, and the ability for real-time imaging. Therefore, combining the imaging information of both modalities can provide comprehensive in vivo physiological and pathological information. However, currently there are limited probes available that can realize both fluorescence and photoacoustic imaging, and advanced biomedical applications for applying this dual-modality imaging approach remain underexplored. In this study, we developed a dual-modality photoacoustic-fluorescence imaging nanoprobe, ICG-loaded Au@SiO2, which was uniquely designed, consisting of gold nanorod cores and indocyanine green with silica shell spacer layers to overcome fluorophore quenching. This nanoprobe was examined by both PAI and FMI for in vivo imaging on tumor and ischemia mouse models. Our results demonstrated that the nanoparticles can specifically accumulate at the tumor and ischemic areas and be detected by both imaging modalities. Moreover, this dual-modality imaging strategy exhibited superior advantages for a precise diagnosis in different scenarios. The new nanoprobe with the dual-modality imaging approach holds great potential for diagnosis and stage classification of tumor and ischemia related diseases.Photoacoustic imaging and fluorescence molecular imaging are emerging as important research tools for biomedical studies. Photoacoustic imaging offers both strong optical absorption contrast and high ultrasonic resolution, and fluorescence molecular imaging provides excellent superficial resolution, high sensitivity, high throughput, and the ability for real-time imaging. Therefore, combining the imaging information of both modalities can provide comprehensive in vivo physiological and pathological information. However, currently there are limited probes available that can realize both fluorescence and photoacoustic imaging, and advanced biomedical applications for applying this dual-modality imaging approach remain underexplored. In this study, we developed a dual-modality photoacoustic-fluorescence imaging nanoprobe, ICG-loaded Au@SiO2, which was uniquely designed, consisting of gold nanorod cores and indocyanine green with silica shell spacer layers to overcome fluorophore quenching. This nanoprobe was examined by both PAI and FMI for in vivo imaging on tumor and ischemia mouse models. Our results demonstrated that the nanoparticles can specifically accumulate at the tumor and ischemic areas and be detected by both imaging modalities. Moreover, this dual-modality imaging strategy exhibited superior advantages for a precise diagnosis in different scenarios. The new nanoprobe with the dual-modality imaging approach holds great potential for diagnosis and stage classification of tumor and ischemia related diseases. Electronic supplementary information (ESI) available. See DOI: 10.1039/c6nr03809c

Identification and super-resolution imaging of ligand-activated receptor dimers in live cells

NASA Astrophysics Data System (ADS)

Winckler, Pascale; Lartigue, Lydia; Giannone, Gregory; de Giorgi, Francesca; Ichas, François; Sibarita, Jean-Baptiste; Lounis, Brahim; Cognet, Laurent

2013-08-01

Molecular interactions are key to many chemical and biological processes like protein function. In many signaling processes they occur in sub-cellular areas displaying nanoscale organizations and involving molecular assemblies. The nanometric dimensions and the dynamic nature of the interactions make their investigations complex in live cells. While super-resolution fluorescence microscopies offer live-cell molecular imaging with sub-wavelength resolutions, they lack specificity for distinguishing interacting molecule populations. Here we combine super-resolution microscopy and single-molecule Förster Resonance Energy Transfer (FRET) to identify dimers of receptors induced by ligand binding and provide super-resolved images of their membrane distribution in live cells. By developing a two-color universal-Point-Accumulation-In-the-Nanoscale-Topography (uPAINT) method, dimers of epidermal growth factor receptors (EGFR) activated by EGF are studied at ultra-high densities, revealing preferential cell-edge sub-localization. This methodology which is specifically devoted to the study of molecules in interaction, may find other applications in biological systems where understanding of molecular organization is crucial.

An Analog Macroscopic Technique for Studying Molecular Hydrodynamic Processes in Dense Gases and Liquids.

PubMed

Dahlberg, Jerry; Tkacik, Peter T; Mullany, Brigid; Fleischhauer, Eric; Shahinian, Hossein; Azimi, Farzad; Navare, Jayesh; Owen, Spencer; Bisel, Tucker; Martin, Tony; Sholar, Jodie; Keanini, Russell G

2017-12-04

An analog, macroscopic method for studying molecular-scale hydrodynamic processes in dense gases and liquids is described. The technique applies a standard fluid dynamic diagnostic, particle image velocimetry (PIV), to measure: i) velocities of individual particles (grains), extant on short, grain-collision time-scales, ii) velocities of systems of particles, on both short collision-time- and long, continuum-flow-time-scales, iii) collective hydrodynamic modes known to exist in dense molecular fluids, and iv) short- and long-time-scale velocity autocorrelation functions, central to understanding particle-scale dynamics in strongly interacting, dense fluid systems. The basic system is composed of an imaging system, light source, vibrational sensors, vibrational system with a known media, and PIV and analysis software. Required experimental measurements and an outline of the theoretical tools needed when using the analog technique to study molecular-scale hydrodynamic processes are highlighted. The proposed technique provides a relatively straightforward alternative to photonic and neutron beam scattering methods traditionally used in molecular hydrodynamic studies.

[Clinical applications of molecular imaging methods for patients with ischemic stroke].

PubMed

Yamauchi, Hiroshi; Fukuyama, Hidenao

2007-02-01

Several molecular imaging methods have been developed to visualize pathophysiology of cerebral ischemia in humans in vivo. PET and SPECT with specific ligands have been mainly used as diagnostic tools for the clinical usage of molecular imaging in patients with ischemic stroke. Recently, cellular MR imaging with specific contrast agents has been developed to visualize targeted cells in human stroke patients. This article reviews the current status in the clinical applications of those molecular imaging methods for patients with ischemic stroke.

Functional optical coherence tomography: principles and progress

NASA Astrophysics Data System (ADS)

Kim, Jina; Brown, William; Maher, Jason R.; Levinson, Howard; Wax, Adam

2015-05-01

In the past decade, several functional extensions of optical coherence tomography (OCT) have emerged, and this review highlights key advances in instrumentation, theoretical analysis, signal processing and clinical application of these extensions. We review five principal extensions: Doppler OCT (DOCT), polarization-sensitive OCT (PS-OCT), optical coherence elastography (OCE), spectroscopic OCT (SOCT), and molecular imaging OCT. The former three have been further developed with studies in both ex vivo and in vivo human tissues. This review emphasizes the newer techniques of SOCT and molecular imaging OCT, which show excellent potential for clinical application but have yet to be well reviewed in the literature. SOCT elucidates tissue characteristics, such as oxygenation and carcinogenesis, by detecting wavelength-dependent absorption and scattering of light in tissues. While SOCT measures endogenous biochemical distributions, molecular imaging OCT detects exogenous molecular contrast agents. These newer advances in functional OCT broaden the potential clinical application of OCT by providing novel ways to understand tissue activity that cannot be accomplished by other current imaging methodologies.

Functional Optical Coherence Tomography: Principles and Progress

PubMed Central

Kim, Jina; Brown, William; Maher, Jason R.; Levinson, Howard; Wax, Adam

2015-01-01

In the past decade, several functional extensions of optical coherence tomography (OCT) have emerged, and this review highlights key advances in instrumentation, theoretical analysis, signal processing and clinical application of these extensions. We review five principal extensions: Doppler OCT (DOCT), polarization-sensitive OCT (PS-OCT), optical coherence elastography (OCE), spectroscopic OCT (SOCT), and molecular imaging OCT. The former three have been further developed with studies in both ex vivo and in vivo human tissues. This review emphasizes the newer techniques of SOCT and molecular imaging OCT, which show excellent potential for clinical application but have yet to be well reviewed in the literature. SOCT elucidates tissue characteristics, such as oxygenation and carcinogenesis, by detecting wavelength-dependent absorption and scattering of light in tissues. While SOCT measures endogenous biochemical distributions, molecular imaging OCT detects exogenous molecular contrast agents. These newer advances in functional OCT broaden the potential clinical application of OCT by providing novel ways to understand tissue activity that cannot be accomplished by other current imaging methodologies. PMID:25951836

Use of micro-positron emission tomography with (18)F-fallypride to measure the levels of dopamine receptor-D2 and (18)F-FDG as molecular imaging tracer in the pituitary glands and prolactinomas of Fischer-344 rats.

PubMed

Li, Ping; Gui, Songbai; Cao, Lei; Gao, Hua; Bai, Jiwei; Li, Chuzhong; Zhang, Yazhuo

2016-01-01

Dopamine receptor-D2 (DRD2) is the most important drug target in prolactinoma. The aim of this current study was to investigate the role of using micro-positron emission tomography (micro-PET) with (18)F-fallypride and (18)F-fluorodeoxyglucose ((18)F-FDG) as molecular imaging tracer in the pituitary glands and prolactinomas of Fischer-344 (F344) rats and detect the difference of the levels of DRD2 in the pituitary glands and prolactinomas of F344 rat prolactinoma models. Female F344 rat prolactinoma models were established by subcutaneous administration of 15 mg 17β-estradiol for 8 weeks. The growth of tumors was monitored by the small-animal magnetic resonance imaging and micro-PET. A series of molecular biological experiments were also performed 4 and 6 weeks after pump implantation. The micro-PET molecular imaging with (18)F-fallypride revealed a decreased expression of DRD2 in F344 rat prolactinoma models, but the micro-PET molecular imaging with (18)F-FDG presented an increased uptake in the prolactinoma compared with the pituitary gland. A decreasing trend of levels of DRD2 in F344 rat prolactinoma models was also detected by molecular biological experiments. From this, we can conclude that micro-PET with (18)F-fallypride and (18)F-FDG can be used to assess tumorigenesis of the prolactinomas in vivo and molecular imaging detection of DRD2 level in prolactinoma may be an indication of treatment effect in the animal experiment.

Molecular medicine: a path towards a personalized medicine.

PubMed

Miranda, Debora Marques de; Mamede, Marcelo; Souza, Bruno Rezende de; Almeida Barros, Alexandre Guimarães de; Magno, Luiz Alexandre; Alvim-Soares, Antônio; Rosa, Daniela Valadão; Castro, Célio José de; Malloy-Diniz, Leandro; Gomez, Marcus Vinícius; Marco, Luiz Armando De; Correa, Humberto; Romano-Silva, Marco Aurélio

2012-03-01

Psychiatric disorders are among the most common human illnesses; still, the molecular and cellular mechanisms underlying their complex pathophysiology remain to be fully elucidated. Over the past 10 years, our group has been investigating the molecular abnormalities in major signaling pathways involved in psychiatric disorders. Recent evidences obtained by the Instituto Nacional de Ciência e Tecnologia de Medicina Molecular (National Institute of Science and Technology - Molecular Medicine, INCT-MM) and others using behavioral analysis of animal models provided valuable insights into the underlying molecular alterations responsible for many complex neuropsychiatric disorders, suggesting that "defects" in critical intracellular signaling pathways have an important role in regulating neurodevelopment, as well as in pathophysiology and treatment efficacy. Resources from the INCT have allowed us to start doing research in the field of molecular imaging. Molecular imaging is a research discipline that visualizes, characterizes, and quantifies the biologic processes taking place at cellular and molecular levels in humans and other living systems through the results of image within the reality of the physiological environment. In order to recognize targets, molecular imaging applies specific instruments (e.g., PET) that enable visualization and quantification in space and in real-time of signals from molecular imaging agents. The objective of molecular medicine is to individualize treatment and improve patient care. Thus, molecular imaging is an additional tool to achieve our ultimate goal.

Molecular Imaging in Synthetic Biology, and Synthetic Biology in Molecular Imaging.

PubMed

Gilad, Assaf A; Shapiro, Mikhail G

2017-06-01

Biomedical synthetic biology is an emerging field in which cells are engineered at the genetic level to carry out novel functions with relevance to biomedical and industrial applications. This approach promises new treatments, imaging tools, and diagnostics for diseases ranging from gastrointestinal inflammatory syndromes to cancer, diabetes, and neurodegeneration. As these cellular technologies undergo pre-clinical and clinical development, it is becoming essential to monitor their location and function in vivo, necessitating appropriate molecular imaging strategies, and therefore, we have created an interest group within the World Molecular Imaging Society focusing on synthetic biology and reporter gene technologies. Here, we highlight recent advances in biomedical synthetic biology, including bacterial therapy, immunotherapy, and regenerative medicine. We then discuss emerging molecular imaging approaches to facilitate in vivo applications, focusing on reporter genes for noninvasive modalities such as magnetic resonance, ultrasound, photoacoustic imaging, bioluminescence, and radionuclear imaging. Because reporter genes can be incorporated directly into engineered genetic circuits, they are particularly well suited to imaging synthetic biological constructs, and developing them provides opportunities for creative molecular and genetic engineering.

Application of Deep Learning in Automated Analysis of Molecular Images in Cancer: A Survey

PubMed Central

Xue, Yong; Chen, Shihui; Liu, Yong

2017-01-01

Molecular imaging enables the visualization and quantitative analysis of the alterations of biological procedures at molecular and/or cellular level, which is of great significance for early detection of cancer. In recent years, deep leaning has been widely used in medical imaging analysis, as it overcomes the limitations of visual assessment and traditional machine learning techniques by extracting hierarchical features with powerful representation capability. Research on cancer molecular images using deep learning techniques is also increasing dynamically. Hence, in this paper, we review the applications of deep learning in molecular imaging in terms of tumor lesion segmentation, tumor classification, and survival prediction. We also outline some future directions in which researchers may develop more powerful deep learning models for better performance in the applications in cancer molecular imaging. PMID:29114182

Molecular Imaging of Pancreatic Cancer with Antibodies

PubMed Central

2015-01-01

Development of novel imaging probes for cancer diagnostics remains critical for early detection of disease, yet most imaging agents are hindered by suboptimal tumor accumulation. To overcome these limitations, researchers have adapted antibodies for imaging purposes. As cancerous malignancies express atypical patterns of cell surface proteins in comparison to noncancerous tissues, novel antibody-based imaging agents can be constructed to target individual cancer cells or surrounding vasculature. Using molecular imaging techniques, these agents may be utilized for detection of malignancies and monitoring of therapeutic response. Currently, there are several imaging modalities commonly employed for molecular imaging. These imaging modalities include positron emission tomography (PET), single-photon emission computed tomography (SPECT), magnetic resonance (MR) imaging, optical imaging (fluorescence and bioluminescence), and photoacoustic (PA) imaging. While antibody-based imaging agents may be employed for a broad range of diseases, this review focuses on the molecular imaging of pancreatic cancer, as there are limited resources for imaging and treatment of pancreatic malignancies. Additionally, pancreatic cancer remains the most lethal cancer with an overall 5-year survival rate of approximately 7%, despite significant advances in the imaging and treatment of many other cancers. In this review, we discuss recent advances in molecular imaging of pancreatic cancer using antibody-based imaging agents. This task is accomplished by summarizing the current progress in each type of molecular imaging modality described above. Also, several considerations for designing and synthesizing novel antibody-based imaging agents are discussed. Lastly, the future directions of antibody-based imaging agents are discussed, emphasizing the potential applications for personalized medicine. PMID:26620581

Development of companion diagnostics

DOE PAGES

Mankoff, David A.; Edmonds, Christine E.; Farwell, Michael D.; ...

2015-12-12

The goal of individualized and targeted treatment and precision medicine requires the assessment of potential therapeutic targets to direct treatment selection. The biomarkers used to direct precision medicine, often termed companion diagnostics, for highly targeted drugs have thus far been almost entirely based on in vitro assay of biopsy material. Molecular imaging companion diagnostics offer a number of features complementary to those from in vitro assay, including the ability to measure the heterogeneity of each patient’s cancer across the entire disease burden and to measure early changes in response to treatment. We discuss the use of molecular imaging methods asmore » companion diagnostics for cancer therapy with the goal of predicting response to targeted therapy and measuring early (pharmacodynamic) response as an indication of whether the treatment has “hit” the target. We also discuss considerations for probe development for molecular imaging companion diagnostics, including both small-molecule probes and larger molecules such as labeled antibodies and related constructs. We then describe two examples where both predictive and pharmacodynamic molecular imaging markers have been tested in humans: endocrine therapy for breast cancer and human epidermal growth factor receptor type 2–targeted therapy. Lastly, the review closes with a summary of the items needed to move molecular imaging companion diagnostics from early studies into multicenter trials and into the clinic.« less

Development of companion diagnostics

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mankoff, David A.; Edmonds, Christine E.; Farwell, Michael D.

The goal of individualized and targeted treatment and precision medicine requires the assessment of potential therapeutic targets to direct treatment selection. The biomarkers used to direct precision medicine, often termed companion diagnostics, for highly targeted drugs have thus far been almost entirely based on in vitro assay of biopsy material. Molecular imaging companion diagnostics offer a number of features complementary to those from in vitro assay, including the ability to measure the heterogeneity of each patient’s cancer across the entire disease burden and to measure early changes in response to treatment. We discuss the use of molecular imaging methods asmore » companion diagnostics for cancer therapy with the goal of predicting response to targeted therapy and measuring early (pharmacodynamic) response as an indication of whether the treatment has “hit” the target. We also discuss considerations for probe development for molecular imaging companion diagnostics, including both small-molecule probes and larger molecules such as labeled antibodies and related constructs. We then describe two examples where both predictive and pharmacodynamic molecular imaging markers have been tested in humans: endocrine therapy for breast cancer and human epidermal growth factor receptor type 2–targeted therapy. Lastly, the review closes with a summary of the items needed to move molecular imaging companion diagnostics from early studies into multicenter trials and into the clinic.« less

Development of Companion Diagnostics

PubMed Central

Mankoff, David A.; Edmonds, Christine E.; Farwell, Michael D.; Pryma, Daniel A.

2016-01-01

The goal of individualized and targeted treatment and precision medicine requires the assessment of potential therapeutic targets to direct treatment selection. The biomarkers used to direct precision medicine, often termed companion diagnostics, for highly targeted drugs have thus far been almost entirely based on in vitro assay of biopsy material. Molecular imaging companion diagnostics offer a number of features complementary to those from in vitro assay, including the ability to measure the heterogeneity of each patient’s cancer across the entire disease burden and to measure early changes in response to treatment. We discuss the use of molecular imaging methods as companion diagnostics for cancer therapy with the goal of predicting response to targeted therapy and measuring early (pharmacodynamic) response as an indication of whether the treatment has “hit” the target. We also discuss considerations for probe development for molecular imaging companion diagnostics, including both small-molecule probes and larger molecules such as labeled antibodies and related constructs. We then describe two examples where both predictive and pharmacodynamic molecular imaging markers have been tested in humans: endocrine therapy for breast cancer and human epidermal growth factor receptor type 2–targeted therapy. The review closes with a summary of the items needed to move molecular imaging companion diagnostics from early studies into multicenter trials and into the clinic. PMID:26687857

High Resolution PET Imaging Probe for the Detection, Molecular Characterization and Treatment Monitoring of Prostate Cancer

DTIC Science & Technology

2010-07-01

W81XWH-09-1-0420 TITLE: High Resolution PET Imaging Probe for the Detection, Molecular Characterization and Treatment Monitoring of Prostate Cancer...4. TITLE AND SUBTITLE High-Resolution PET Imaging Probe for the Detection, Molecular Characterization and Treatment of Prostate Cancer... molecular imaging for diagnosis as well as treatment planning and monitoring in prostate cancer. This investigation hypothesizes that a dedicated

Automation and Preclinical Evaluation of a Dedicated Emission Mammotomography System for Fully 3-D Molecular Breast Imaging

DTIC Science & Technology

2009-10-01

molecular breast imaging, with the ability to dynamically contour any sized breast, will improve detection and potentially in vivo characterization of...Having flexible 3D positioning about the breast yielded minimal RMSD differences, which is important for high resolution molecular emission imaging. This...TITLE: Automation and Preclinical Evaluation of a Dedicated Emission Mammotomography System for Fully 3-D Molecular Breast Imaging PRINCIPAL

Progress toward time-resolved molecular imaging: A theoretical study of optimal parameters in static photoelectron holography

NASA Astrophysics Data System (ADS)

Sun, S. X.-L.; Kaduwela, A. P.; Gray, A. X.; Fadley, C. S.

2014-05-01

The availability of short-pulse free-electron lasers has led to the idea of using photoelectron holography as a method of directly imaging molecular dissociations or reactions in real time, as, e.g., in a recent theoretical study by Krasniqi et al., [F. Krasniqi, B. Najjari, L. Strüder, D. Rolles, A. Voitkiv, and J. Ullrich, Phys. Rev. A 81, 033411 (2010), 10.1103/PhysRevA.81.033411]. In this paper, we extend this earlier work and in particular look at two critical questions concerning the optimum type of data required for such holographic imaging: the choice of photoelectron kinetic energy (e.g., ˜300 eV versus ˜1700 eV as in the prior study), and the use of a single energy or multiple energies. After verifying that our calculations fully duplicate those in this prior paper, we show that using lower energies is preferable to using higher energies for image quality, a conclusion consistent with prior photoelectron holography studies at surfaces, and that multiple lower energies in which the hologram effectively spans a volume in kspace yields the best quality images that should be useful for such "molecular movies." Although the amount of data required for such multi-energy holography is roughly an order of magnitude higher than that for single energy, the reduction of artifacts and the improved quality of the images suggest this as the optimum ultimate future strategy for such dynamic imaging.

Imaging Neuroinflammation – from Bench to Bedside

PubMed Central

Pulli, Benjamin; Chen, John W

2014-01-01

Neuroinflammation plays a central role in a variety of neurological diseases, including stroke, multiple sclerosis, Alzheimer’s disease, and malignant CNS neoplasms, among many other. Different cell types and molecular mediators participate in a cascade of events in the brain that is ultimately aimed at control, regeneration and repair, but leads to damage of brain tissue under pathological conditions. Non-invasive molecular imaging of key players in the inflammation cascade holds promise for identification and quantification of the disease process before it is too late for effective therapeutic intervention. In this review, we focus on molecular imaging techniques that target inflammatory cells and molecules that are of interest in neuroinflammation, especially those with high translational potential. Over the past decade, a plethora of molecular imaging agents have been developed and tested in animal models of (neuro)inflammation, and a few have been translated from bench to bedside. The most promising imaging techniques to visualize neuroinflammation include MRI, positron emission tomography (PET), single photon emission computed tomography (SPECT), and optical imaging methods. These techniques enable us to image adhesion molecules to visualize endothelial cell activation, assess leukocyte functions such as oxidative stress, granule release, and phagocytosis, and label a variety of inflammatory cells for cell tracking experiments. In addition, several cell types and their activation can be specifically targeted in vivo, and consequences of neuroinflammation such as neuronal death and demyelination can be quantified. As we continue to make progress in utilizing molecular imaging technology to study and understand neuroinflammation, increasing efforts and investment should be made to bring more of these novel imaging agents from the “bench to bedside.” PMID:25525560

Fluorescence Molecular Tomography: Principles and Potential for Pharmaceutical Research

PubMed Central

Stuker, Florian; Ripoll, Jorge; Rudin, Markus

2011-01-01

Fluorescence microscopic imaging is widely used in biomedical research to study molecular and cellular processes in cell culture or tissue samples. This is motivated by the high inherent sensitivity of fluorescence techniques, the spatial resolution that compares favorably with cellular dimensions, the stability of the fluorescent labels used and the sophisticated labeling strategies that have been developed for selectively labeling target molecules. More recently, two and three-dimensional optical imaging methods have also been applied to monitor biological processes in intact biological organisms such as animals or even humans. These whole body optical imaging approaches have to cope with the fact that biological tissue is a highly scattering and absorbing medium. As a consequence, light propagation in tissue is well described by a diffusion approximation and accurate reconstruction of spatial information is demanding. While in vivo optical imaging is a highly sensitive method, the signal is strongly surface weighted, i.e., the signal detected from the same light source will become weaker the deeper it is embedded in tissue, and strongly depends on the optical properties of the surrounding tissue. Derivation of quantitative information, therefore, requires tomographic techniques such as fluorescence molecular tomography (FMT), which maps the three-dimensional distribution of a fluorescent probe or protein concentration. The combination of FMT with a structural imaging method such as X-ray computed tomography (CT) or Magnetic Resonance Imaging (MRI) will allow mapping molecular information on a high definition anatomical reference and enable the use of prior information on tissue's optical properties to enhance both resolution and sensitivity. Today many of the fluorescent assays originally developed for studies in cellular systems have been successfully translated for experimental studies in animals. The opportunity of monitoring molecular processes non-invasively in the intact organism is highly attractive from a diagnostic point of view but even more so for the drug developer, who can use the techniques for proof-of-mechanism and proof-of-efficacy studies. This review shall elucidate the current status and potential of fluorescence tomography including recent advances in multimodality imaging approaches for preclinical and clinical drug development. PMID:24310495

Ultrasound Molecular Imaging: Moving Towards Clinical Translation

PubMed Central

Abou-Elkacem, Lotfi; Bachawal, Sunitha V.; Willmann, Jürgen K.

2015-01-01

Ultrasound is a widely available, cost-effective, real-time, non-invasive and safe imaging modality widely used in the clinic for anatomical and functional imaging. With the introduction of novel molecularly-targeted ultrasound contrast agents, another dimension of ultrasound has become a reality: diagnosing and monitoring pathological processes at the molecular level. Most commonly used ultrasound molecular imaging contrast agents are micron sized, gas-containing microbubbles functionalized to recognize and attach to molecules expressed on inflamed or angiogenic vascular endothelial cells. There are several potential clinical applications currently being explored including earlier detection, molecular profiling, and monitoring of cancer, as well as visualization of ischemic memory in transient myocardial ischemia, monitoring of disease activity in inflammatory bowel disease, and assessment of arteriosclerosis. Recently, a first clinical grade ultrasound contrast agent (BR55), targeted at a molecule expressed in neoangiogenesis (vascular endothelial growth factor receptor type 2; VEGFR2) has been introduced and safety and feasibility of VEGFR2-targeted ultrasound imaging is being explored in first inhuman clinical trials in various cancer types. This review describes the design of ultrasound molecular imaging contrast agents, imaging techniques, and potential future clinical applications of ultrasound molecular imaging. PMID:25851932

Ultrasound molecular imaging: Moving toward clinical translation.

PubMed

Abou-Elkacem, Lotfi; Bachawal, Sunitha V; Willmann, Jürgen K

2015-09-01

Ultrasound is a widely available, cost-effective, real-time, non-invasive and safe imaging modality widely used in the clinic for anatomical and functional imaging. With the introduction of novel molecularly-targeted ultrasound contrast agents, another dimension of ultrasound has become a reality: diagnosing and monitoring pathological processes at the molecular level. Most commonly used ultrasound molecular imaging contrast agents are micron sized, gas-containing microbubbles functionalized to recognize and attach to molecules expressed on inflamed or angiogenic vascular endothelial cells. There are several potential clinical applications currently being explored including earlier detection, molecular profiling, and monitoring of cancer, as well as visualization of ischemic memory in transient myocardial ischemia, monitoring of disease activity in inflammatory bowel disease, and assessment of arteriosclerosis. Recently, a first clinical grade ultrasound contrast agent (BR55), targeted at a molecule expressed in neoangiogenesis (vascular endothelial growth factor receptor type 2; VEGFR2) has been introduced and safety and feasibility of VEGFR2-targeted ultrasound imaging is being explored in first inhuman clinical trials in various cancer types. This review describes the design of ultrasound molecular imaging contrast agents, imaging techniques, and potential future clinical applications of ultrasound molecular imaging. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Illuminating necrosis: From mechanistic exploration to preclinical application using fluorescence molecular imaging with indocyanine green

PubMed Central

Fang, Cheng; Wang, Kun; Zeng, Chaoting; Chi, Chongwei; Shang, Wenting; Ye, Jinzuo; Mao, Yamin; Fan, Yingfang; Yang, Jian; Xiang, Nan; Zeng, Ning; Zhu, Wen; Fang, Chihua; Tian, Jie

2016-01-01

Tissue necrosis commonly accompanies the development of a wide range of serious diseases. Therefore, highly sensitive detection and precise boundary delineation of necrotic tissue via effective imaging techniques are crucial for clinical treatments; however, no imaging modalities have achieved satisfactory results to date. Although fluorescence molecular imaging (FMI) shows potential in this regard, no effective necrosis-avid fluorescent probe has been developed for clinical applications. Here, we demonstrate that indocyanine green (ICG) can achieve high avidity of necrotic tissue owing to its interaction with lipoprotein (LP) and phospholipids. The mechanism was explored at the cellular and molecular levels through a series of in vitro studies. Detection of necrotic tissue and real-time image-guided surgery were successfully achieved in different organs of different animal models with the help of FMI using in house-designed imaging devices. The results indicated that necrotic tissue with a 0.6 mm diameter could be effectively detected with precise boundary definition. We believe that the new discovery and the associated imaging techniques will improve personalized and precise surgery in the near future. PMID:26864116

Determination of three-dimensional molecular orientation of type-I collagen by circularly-polarized second harmonic generation imaging

NASA Astrophysics Data System (ADS)

Zhuo, Guan-Yu; Hung, Wei-Han; Kao, Fu-Jen

2017-04-01

The content of collagen is up to 30% existing in mammals. It supports the main component of connective tissues such as skin, ligament, and cartilage. Among various types of collagen, type-I collagen is of the most abundance and has been broadly studied due to the importance in bioscience. Second harmonic generation (SHG) microscopy is an effective tool used to study the collagen organization without labeling. In this study, we used circular polarization instead of linear polarization to retrieve three-dimensional (3D) molecular orientation of type-I collagen with only two cross polarized SHG images without acquiring an image stack of varying polarization.

Current perspectives in the use of molecular imaging to target surgical treatments for genitourinary cancers.

PubMed

Greco, Francesco; Cadeddu, Jeffrey A; Gill, Inderbir S; Kaouk, Jihad H; Remzi, Mesut; Thompson, R Houston; van Leeuwen, Fijs W B; van der Poel, Henk G; Fornara, Paolo; Rassweiler, Jens

2014-05-01

Molecular imaging (MI) entails the visualisation, characterisation, and measurement of biologic processes at the molecular and cellular levels in humans and other living systems. Translating this technology to interventions in real-time enables interventional MI/image-guided surgery, for example, by providing better detection of tumours and their dimensions. To summarise and critically analyse the available evidence on image-guided surgery for genitourinary (GU) oncologic diseases. A comprehensive literature review was performed using PubMed and the Thomson Reuters Web of Science. In the free-text protocol, the following terms were applied: molecular imaging, genitourinary oncologic surgery, surgical navigation, image-guided surgery, and augmented reality. Review articles, editorials, commentaries, and letters to the editor were included if deemed to contain relevant information. We selected 79 articles according to the search strategy based on the Preferred Reporting Items for Systematic Reviews and Meta-analysis criteria and the IDEAL method. MI techniques included optical imaging and fluorescent techniques, the augmented reality (AR) navigation system, magnetic resonance imaging spectroscopy, positron emission tomography, and single-photon emission computed tomography. Experimental studies on the AR navigation system were restricted to the detection and therapy of adrenal and renal malignancies and in the relatively infrequent cases of prostate cancer, whereas fluorescence techniques and optical imaging presented a wide application of intraoperative GU oncologic surgery. In most cases, image-guided surgery was shown to improve the surgical resectability of tumours. Based on the evidence to date, image-guided surgery has promise in the near future for multiple GU malignancies. Further optimisation of targeted imaging agents, along with the integration of imaging modalities, is necessary to further enhance intraoperative GU oncologic surgery. Copyright © 2013 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Cryo-Imaging and Software Platform for Analysis of Molecular MR Imaging of Micrometastases

PubMed Central

Qutaish, Mohammed Q.; Zhou, Zhuxian; Prabhu, David; Liu, Yiqiao; Busso, Mallory R.; Izadnegahdar, Donna; Gargesha, Madhusudhana; Lu, Hong; Lu, Zheng-Rong

2018-01-01

We created and evaluated a preclinical, multimodality imaging, and software platform to assess molecular imaging of small metastases. This included experimental methods (e.g., GFP-labeled tumor and high resolution multispectral cryo-imaging), nonrigid image registration, and interactive visualization of imaging agent targeting. We describe technological details earlier applied to GFP-labeled metastatic tumor targeting by molecular MR (CREKA-Gd) and red fluorescent (CREKA-Cy5) imaging agents. Optimized nonrigid cryo-MRI registration enabled nonambiguous association of MR signals to GFP tumors. Interactive visualization of out-of-RAM volumetric image data allowed one to zoom to a GFP-labeled micrometastasis, determine its anatomical location from color cryo-images, and establish the presence/absence of targeted CREKA-Gd and CREKA-Cy5. In a mouse with >160 GFP-labeled tumors, we determined that in the MR images every tumor in the lung >0.3 mm2 had visible signal and that some metastases as small as 0.1 mm2 were also visible. More tumors were visible in CREKA-Cy5 than in CREKA-Gd MRI. Tape transfer method and nonrigid registration allowed accurate (<11 μm error) registration of whole mouse histology to corresponding cryo-images. Histology showed inflammation and necrotic regions not labeled by imaging agents. This mouse-to-cells multiscale and multimodality platform should uniquely enable more informative and accurate studies of metastatic cancer imaging and therapy. PMID:29805438

Molecular imaging for theranostics in gastroenterology: one stone to kill two birds.

PubMed

Ko, Kwang Hyun; Kown, Chang-Il; Park, Jong Min; Lee, Hoo Geun; Han, Na Young; Hahm, Ki Baik

2014-09-01

Molecular imaging in gastroenterology has become more feasible with recent advances in imaging technology, molecular genetics, and next-generation biochemistry, in addition to advances in endoscopic imaging techniques including magnified high-resolution endoscopy, narrow band imaging or autofluorescence imaging, flexible spectral imaging color enhancement, and confocal laser endomicroscopy. These developments have the potential to serve as "red flag" techniques enabling the earlier and accurate detection of mucosal abnormalities (such as precancerous lesions) beyond biomarkers, virtual histology of detected lesions, and molecular targeted therapy-the strategy of "one stone to kill two or three birds"; however, more effort should be done to be "blue ocean" benefit. This review deals with the introduction of Raman spectroscopy endoscopy, imaging mass spectroscopy, and nanomolecule development for theranostics. Imaging of molecular pathological changes in cells/tissues/organs might open the "royal road" to either convincing diagnosis of diseases that otherwise would only be detected in the advanced stages or novel therapeutic methods targeted to personalized medicine.

An Update on in Vivo Imaging of Extracellular Vesicles as Drug Delivery Vehicles

PubMed Central

Gangadaran, Prakash; Hong, Chae Moon; Ahn, Byeong-Cheol

2018-01-01

Extracellular vesicles (EVs) are currently being considered as promising drug delivery vehicles. EVs are naturally occurring vesicles that exhibit many characteristics favorable to serve as drug delivery vehicles. In addition, EVs have inherent properties for treatment of cancers and other diseases. For research and clinical translation of use of EVs as drug delivery vehicles, in vivo tracking of EVs is essential. The latest molecular imaging techniques enable the tracking of EVs in living animals. However, each molecular imaging technique has its certain advantages and limitations for the in vivo imaging of EVs; therefore, understanding the molecular imaging techniques is essential to select the most appropriate imaging technology to achieve the desired imaging goal. In this review, we summarize the characteristics of EVs as drug delivery vehicles and the molecular imaging techniques used in visualizing and monitoring EVs in in vivo environments. Furthermore, we provide a perceptual vision of EVs as drug delivery vehicles and in vivo monitoring of EVs using molecular imaging technologies. PMID:29541030

Low-intensity focused ultrasound (LIFU)-induced acoustic droplet vaporization in phase-transition perfluoropentane nanodroplets modified by folate for ultrasound molecular imaging.

PubMed

Liu, Jianxin; Shang, Tingting; Wang, Fengjuan; Cao, Yang; Hao, Lan; Ren, JianLi; Ran, Haitao; Wang, Zhigang; Li, Pan; Du, Zhiyu

2017-01-01

The commonly used ultrasound (US) molecular probes, such as targeted microbubbles and perfluorocarbon emulsions, present a number of inherent problems including the conflict between US visualization and particle penetration. This study describes the successful fabrication of phase changeable folate-targeted perfluoropentane nanodroplets (termed FA-NDs), a novel US molecular probe for tumor molecular imaging with US. Notably, these FA-NDs can be triggered by low-intensity focused US (LIFU) sonication, providing excellent US enhancement in B-mode and contrast-enhanced US mode in vitro. After intravenous administration into nude mice bearing SKOV3 ovarian carcinomas, 1,1'-dioctadecyl-3,3,3',3' -tetramethylindotricarbocya-nine iodide-labeled FA-NDs were found to accumulate in the tumor region. FA-NDs injection followed by LIFU sonication exhibited remarkable US contrast enhancement in the tumor region. In conclusion, combining our elaborately developed FA-NDs with LIFU sonication provides a potential protocol for US molecular imaging in folate receptor-overexpressing tumors.

Low-intensity focused ultrasound (LIFU)-induced acoustic droplet vaporization in phase-transition perfluoropentane nanodroplets modified by folate for ultrasound molecular imaging

PubMed Central

Liu, Jianxin; Shang, Tingting; Wang, Fengjuan; Cao, Yang; Hao, Lan; Ren, JianLi; Ran, Haitao; Wang, Zhigang; Li, Pan; Du, Zhiyu

2017-01-01

The commonly used ultrasound (US) molecular probes, such as targeted microbubbles and perfluorocarbon emulsions, present a number of inherent problems including the conflict between US visualization and particle penetration. This study describes the successful fabrication of phase changeable folate-targeted perfluoropentane nanodroplets (termed FA-NDs), a novel US molecular probe for tumor molecular imaging with US. Notably, these FA-NDs can be triggered by low-intensity focused US (LIFU) sonication, providing excellent US enhancement in B-mode and contrast-enhanced US mode in vitro. After intravenous administration into nude mice bearing SKOV3 ovarian carcinomas, 1,1′-dioctadecyl-3,3,3′,3′ -tetramethylindotricarbocya-nine iodide-labeled FA-NDs were found to accumulate in the tumor region. FA-NDs injection followed by LIFU sonication exhibited remarkable US contrast enhancement in the tumor region. In conclusion, combining our elaborately developed FA-NDs with LIFU sonication provides a potential protocol for US molecular imaging in folate receptor-overexpressing tumors. PMID:28184161

Non-invasive molecular imaging for preclinical cancer therapeutic development

PubMed Central

O'Farrell, AC; Shnyder, SD; Marston, G; Coletta, PL; Gill, JH

2013-01-01

Molecular and non-invasive imaging are rapidly emerging fields in preclinical cancer drug discovery. This is driven by the need to develop more efficacious and safer treatments, the advent of molecular-targeted therapeutics, and the requirements to reduce and refine current preclinical in vivo models. Such bioimaging strategies include MRI, PET, single positron emission computed tomography, ultrasound, and optical approaches such as bioluminescence and fluorescence imaging. These molecular imaging modalities have several advantages over traditional screening methods, not least the ability to quantitatively monitor pharmacodynamic changes at the cellular and molecular level in living animals non-invasively in real time. This review aims to provide an overview of non-invasive molecular imaging techniques, highlighting the strengths, limitations and versatility of these approaches in preclinical cancer drug discovery and development. PMID:23488622

Justifying molecular images in cell biology textbooks: From constructions to primary data.

PubMed

Serpente, Norberto

2016-02-01

For scientific claims to be reliable and productive they have to be justified. However, on the one hand little is known on what justification precisely means to scientists, and on the other the position held by philosophers of science on what it entails is rather limited; for justifications customarily refer to the written form (textual expressions) of scientific claims, leaving aside images, which, as many cases from the history of science show are relevant to this process. The fact that images can visually express scientific claims independently from text, plus their vast variety and origins, requires an assessment of the way they are currently justified and in turn used as sources to justify scientific claims in the case of particular scientific fields. Similarly, in view of the different nature of images, analysis is required to determine on what side of the philosophical distinction between data and phenomena these different kinds of images fall. This paper historicizes and documents a particular aspect of contemporary life sciences research: the use of the molecular image as vehicle of knowledge production in cell studies, a field that has undergone a significant shift in visual expressions from the early 1980s onwards. Focussing on textbooks as sources that have been overlooked in the historiography of contemporary biomedicine, the aim is to explore (1) whether the shift of cell studies, entailing a superseding of the optical image traditionally conceptualised as primary data, by the molecular image, corresponds with a shift of justificatory practices, and (2) to assess the role of the molecular image as primary data. This paper also explores the dual role of images as teaching resources and as resources for the construction of knowledge in cell studies especially in its relation to discovery and justification. Finally, this paper seeks to stimulate reflection on what kind of archival resources could benefit the work of present and future epistemic historians in particular those interested on the role of images as sources of training and knowledge production in scientific disciplines. Copyright © 2015 Elsevier Ltd. All rights reserved.

Automated tumor analysis for molecular profiling in lung cancer

PubMed Central

Boyd, Clinton; James, Jacqueline A.; Loughrey, Maurice B.; Hougton, Joseph P.; Boyle, David P.; Kelly, Paul; Maxwell, Perry; McCleary, David; Diamond, James; McArt, Darragh G.; Tunstall, Jonathon; Bankhead, Peter; Salto-Tellez, Manuel

2015-01-01

The discovery and clinical application of molecular biomarkers in solid tumors, increasingly relies on nucleic acid extraction from FFPE tissue sections and subsequent molecular profiling. This in turn requires the pathological review of haematoxylin & eosin (H&E) stained slides, to ensure sample quality, tumor DNA sufficiency by visually estimating the percentage tumor nuclei and tumor annotation for manual macrodissection. In this study on NSCLC, we demonstrate considerable variation in tumor nuclei percentage between pathologists, potentially undermining the precision of NSCLC molecular evaluation and emphasising the need for quantitative tumor evaluation. We subsequently describe the development and validation of a system called TissueMark for automated tumor annotation and percentage tumor nuclei measurement in NSCLC using computerized image analysis. Evaluation of 245 NSCLC slides showed precise automated tumor annotation of cases using Tissuemark, strong concordance with manually drawn boundaries and identical EGFR mutational status, following manual macrodissection from the image analysis generated tumor boundaries. Automated analysis of cell counts for % tumor measurements by Tissuemark showed reduced variability and significant correlation (p < 0.001) with benchmark tumor cell counts. This study demonstrates a robust image analysis technology that can facilitate the automated quantitative analysis of tissue samples for molecular profiling in discovery and diagnostics. PMID:26317646

Featured Image: A Molecular Cloud Outside Our Galaxy

NASA Astrophysics Data System (ADS)

Kohler, Susanna

2018-06-01

What do molecular clouds look like outside of our own galaxy? See for yourself in the images above and below of N55, a molecular cloud located in the Large Magellanic Cloud (LMC). In a recent study led by Naslim Neelamkodan (Academia Sinica Institute of Astronomy and Astrophysics, Taiwan), a team of scientists explore N55 to determine how its cloud properties differ from clouds within the Milky Way. The image above reveals the distribution of infrared-emitting gas and dust observed in three bands by the Spitzer Space Telescope. Overplotted in cyan are observations from the Atacama Submillimeter Telescope Experiment tracing the clumpy, warm molecular gas. Below, new observations from the Atacama Large Millimeter/submillimeter Array (ALMA) reveal the sub-parsec-scale molecular clumps in greater detail, showing the correlation of massive clumps with Spitzer-identified young stellar objects (crosses). The study presented here indicates that this cloud in the LMC is the site of massive star formation, with properties similar to equivalent clouds in the Milky Way. To learn more about the authors findings, check out the article linked below.CitationNaslim N. et al 2018 ApJ 853 175. doi:10.3847/1538-4357/aaa5b0

Neurobiology of Chronic Stress-Related Psychiatric Disorders: Evidence from Molecular Imaging Studies

PubMed Central

Davis, Margaret T.; Holmes, Sophie E.; Pietrzak, Robert H.; Esterlis, Irina

2018-01-01

Chronic stress accounts for billions of dollars of economic loss annually in the United States alone, and is recognized as a major source of disability and mortality worldwide. Robust evidence suggests that chronic stress plays a significant role in the onset of severe and impairing psychiatric conditions, including major depressive disorder, bipolar disorder, and posttraumatic stress disorder. Application of molecular imaging techniques such as positron emission tomography and single photon emission computed tomography in recent years has begun to provide insight into the molecular mechanisms by which chronic stress confers risk for these disorders. The present paper provides a comprehensive review and synthesis of all positron emission tomography and single photon emission computed tomography imaging publications focused on the examination of molecular targets in individuals with major depressive disorder, posttraumatic stress disorder, or bipolar disorder to date. Critical discussion of discrepant findings and broad strengths and weaknesses of the current body of literature is provided. Recommended future directions for the field of molecular imaging to further elucidate the neurobiological substrates of chronic stress-related disorders are also discussed. This article is part of the inaugural issue for the journal focused on various aspects of chronic stress. PMID:29862379

Frequency Domain Fluorescent Molecular Tomography and Molecular Probes for Small Animal Imaging

NASA Astrophysics Data System (ADS)

Kujala, Naresh Gandhi

Fluorescent molecular tomography (FMT) is a noninvasive biomedical optical imaging that enables 3-dimensional quantitative determination of fluorochromes distributed in biological tissues. There are three methods for imaging large volume tissues based on different light sources: (a) using a light source of constant intensity, through a continuous or constant wave, (b) using a light source that is intensity modulated with a radio frequency (RF), and (c) using ultrafast pulses in the femtosecond range. In this study, we have developed a frequency domain fluorescent molecular tomographic system based on the heterodyne technique, using a single source and detector pair that can be used for small animal imaging. In our system, the intensity of the laser source is modulated with a RF frequency to produce a diffuse photon density wave in the tissue. The phase of the diffuse photon density wave is measured by comparing the reference signal with the signal from the tissue using a phasemeter. The data acquisition was performed by using a Labview program. The results suggest that we can measure the phase change from the heterogeneous inside tissue. Combined with fiber optics and filter sets, the system can be used to sensitively image the targeted fluorescent molecular probes, allowing the detection of cancer at an early stage. We used the system to detect the tumor-targeting molecular probe Alexa Fluor 680 and Alexa Fluor 750 bombesin peptide conjugates in phantoms as well as mouse tissues. We also developed and evaluated fluorescent Bombesin (BBN) probes to target gastrin-releasing peptide (GRP) receptors for optical molecular imaging. GRP receptors are over-expressed in several types of human cancer cells, including breast, prostate, small cell lung, and pancreatic cancers. BBN is a 14 amino acid peptide that is an analogue to human gastrin-releasing peptide that binds specifically to GRPr receptors. BBN conjugates are significant in cancer detection and therapy. The optical molecular probe AF750 BBN peptide exhibits optimal pharmacokinetic properties for targeting GRPr in mice. Fluorescent microscopic imaging of the molecular probe in PC-3 prostate and T-47D breast cancer cell lines indicated specific uptake, internalization, and receptor blocking of these probes. In vivo investigations in severely compromised immunodeficient (SCID) mice bearing xenografted PC-3 prostate and T47-D breast cancer lesions demonstrated the ability of this new molecular probe to specifically target tumor tissue with high selectively and affinity.

Exogenous Molecular Probes for Targeted Imaging in Cancer: Focus on Multi-modal Imaging

PubMed Central

Joshi, Bishnu P.; Wang, Thomas D.

2010-01-01

Cancer is one of the major causes of mortality and morbidity in our healthcare system. Molecular imaging is an emerging methodology for the early detection of cancer, guidance of therapy, and monitoring of response. The development of new instruments and exogenous molecular probes that can be labeled for multi-modality imaging is critical to this process. Today, molecular imaging is at a crossroad, and new targeted imaging agents are expected to broadly expand our ability to detect and manage cancer. This integrated imaging strategy will permit clinicians to not only localize lesions within the body but also to manage their therapy by visualizing the expression and activity of specific molecules. This information is expected to have a major impact on drug development and understanding of basic cancer biology. At this time, a number of molecular probes have been developed by conjugating various labels to affinity ligands for targeting in different imaging modalities. This review will describe the current status of exogenous molecular probes for optical, scintigraphic, MRI and ultrasound imaging platforms. Furthermore, we will also shed light on how these techniques can be used synergistically in multi-modal platforms and how these techniques are being employed in current research. PMID:22180839

Using Single-Protein Tracking to Study Cell Migration.

PubMed

Orré, Thomas; Mehidi, Amine; Massou, Sophie; Rossier, Olivier; Giannone, Grégory

2018-01-01

To get a complete understanding of cell migration, it is critical to study its orchestration at the molecular level. Since the recent developments in single-molecule imaging, it is now possible to study molecular phenomena at the single-molecule level inside living cells. In this chapter, we describe how such approaches have been and can be used to decipher molecular mechanisms involved in cell migration.

NanoLuc reporter for dual luciferase imaging in living animals.

PubMed

Stacer, Amanda C; Nyati, Shyam; Moudgil, Pranav; Iyengar, Rahul; Luker, Kathryn E; Rehemtulla, Alnawaz; Luker, Gary D

2013-10-01

Bioluminescence imaging is widely used for cell-based assays and animal imaging studies in biomedical research and drug development, capitalizing on the high signal to background of this technique. A relatively small number of luciferases are available for imaging studies, substantially limiting the ability to image multiple molecular and cellular events, as done commonly with fluorescence imaging. To advance dual reporter bioluminescence molecular imaging, we tested a recently developed, adenosine triphosphate–independent luciferase enzyme from Oplophorus gracilirostris (NanoLuc [NL]) as a reporter for animal imaging. We demonstrated that NL could be imaged in superficial and deep tissues in living mice, although the detection of NL in deep tissues was limited by emission of predominantly blue light by this enzyme. Changes in bioluminescence from NL over time could be used to quantify tumor growth, and secreted NL was detectable in small volumes of serum. We combined NL and firefly luciferase reporters to quantify two key steps in transforming growth factor β signaling in intact cells and living mice, establishing a novel dual luciferase imaging strategy for quantifying signal transduction and drug targeting. Our results establish NL as a new reporter for bioluminescence imaging studies in intact cells and living mice that will expand imaging of signal transduction in normal physiology, disease, and drug development.

NanoLuc Reporter for Dual Luciferase Imaging in Living Animals

PubMed Central

Stacer, Amanda C.; Nyati, Shyam; Moudgil, Pranav; Iyengar, Rahul; Luker, Kathryn E.; Rehemtulla, Alnawaz; Luker, Gary D.

2014-01-01

Bioluminescence imaging is utilized widely for cell-based assays and animal imaging studies in biomedical research and drug development, capitalizing on high signal-to-background of this technique. A relatively small number of luciferases are available for imaging studies, substantially limiting the ability to image multiple molecular and cellular events as done commonly with fluorescence imaging. To advance dual reporter bioluminescence molecular imaging, we tested a recently developed, ATP-independent luciferase enzyme from Oplophorus gracilirostris (NanoLuc, NL) as a reporter for animal imaging. We demonstrated that NL could be imaged in superficial and deep tissues in living mice, although detection of NL in deep tissues was limited by emission of predominantly blue light by this enzyme. Changes in bioluminescence from NL over time could be used to quantify tumor growth, and secreted NL was detectable in small volumes of serum. We combined NL and firefly luciferase reporters to quantify two key steps in TGF-β signaling in intact cells and living mice, establishing a novel dual luciferase imaging strategy for quantifying signal transduction and drug targeting. Our results establish NL as new reporter for bioluminescence imaging studies in intact cells and living mice that will expand imaging of signal transduction in normal physiology, disease, and drug development. PMID:24371848

Dual-Modality, Dual-Functional Nanoprobes for Cellular and Molecular Imaging

PubMed Central

Menon, Jyothi U.; Gulaka, Praveen K.; McKay, Madalyn A.; Geethanath, Sairam; Liu, Li; Kodibagkar, Vikram D.

2012-01-01

An emerging need for evaluation of promising cellular therapies is a non-invasive method to image the movement and health of cells following transplantation. However, the use of a single modality to serve this purpose may not be advantageous as it may convey inaccurate or insufficient information. Multi-modal imaging strategies are becoming more popular for in vivo cellular and molecular imaging because of their improved sensitivity, higher resolution and structural/functional visualization. This study aims at formulating Nile Red doped hexamethyldisiloxane (HMDSO) nanoemulsions as dual modality (Magnetic Resonance Imaging/Fluorescence), dual-functional (oximetry/detection) nanoprobes for cellular and molecular imaging. HMDSO nanoprobes were prepared using a HS15-lecithin combination as surfactant and showed an average radius of 71±39 nm by dynamic light scattering and in vitro particle stability in human plasma over 24 hrs. They were found to readily localize in the cytosol of MCF7-GFP cells within 18 minutes of incubation. As proof of principle, these nanoprobes were successfully used for fluorescence imaging and for measuring pO2 changes in cells by magnetic resonance imaging, in vitro, thus showing potential for in vivo applications. PMID:23382776

Molecular Imaging and Quantitation of EphA2 Expression in Xenograft Models with 89Zr-DS-8895a.

PubMed

Burvenich, Ingrid J G; Parakh, Sagun; Gan, Hui K; Lee, Fook-Thean; Guo, Nancy; Rigopoulos, Angela; Lee, Sze-Ting; Gong, Sylvia; O'Keefe, Graeme J; Tochon-Danguy, Henri; Kotsuma, Masakatsu; Hasegawa, Jun; Senaldi, Giorgio; Scott, Andrew M

2016-06-01

Subtype A2 of the erythropoietin-producing hepatocellular tyrosine kinase (EphA2) cell surface receptor is expressed in a range of epithelial cancers. This study evaluated the molecular imaging of EphA2 expression in vivo in mouse tumor models using SPECT/MR and PET/MR and a humanized anti-EphA2 antibody, DS-8895a. DS-8895a was labeled with (111)In, (125)I, and (89)Zr and assessed for radiochemical purity, immunoreactivity (Lindmo analysis), antigen-binding affinity (Scatchard analysis), and serum stability in vitro. In vivo biodistribution, imaging, and pharmacokinetic studies were performed with SPECT/MR and PET/MR. A dose-escalation study was also performed to determine EphA2 receptor saturability through tissue and imaging quantitative analysis. All conjugates demonstrated good serum stability and specific binding to EphA2-expressing cells in vitro. In vivo biodistribution studies showed high uptake of (111)In-CHX-A″-DTPA-DS-8895a and (89)Zr-Df-Bz-NCS-DS-8895a in EphA2-expressing xenograft models, with no specific uptake in normal tissues. In comparison, retention of (125)I-DS-8895a in tumors was lower because of internalization of the radioconjugate and dehalogenation. These results were confirmed by SPECT/MR and PET/MR. EphA2 receptor saturation was observed at the 30 mg/kg dose. Molecular imaging of tumor uptake of DS-8895a allows noninvasive measurement of EphA2 expression in tumors in vivo and determination of receptor saturation. (89)Zr-Df-Bz-NCS-DS-8895a is suited for human bioimaging trials on the basis of superior imaging characteristics and will inform DS-8895a dose assessment and patient response evaluation in clinical trials. © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Intraoperative imaging-guided cancer surgery: from current fluorescence molecular imaging methods to future multi-modality imaging technology.

PubMed

Chi, Chongwei; Du, Yang; Ye, Jinzuo; Kou, Deqiang; Qiu, Jingdan; Wang, Jiandong; Tian, Jie; Chen, Xiaoyuan

2014-01-01

Cancer is a major threat to human health. Diagnosis and treatment using precision medicine is expected to be an effective method for preventing the initiation and progression of cancer. Although anatomical and functional imaging techniques such as radiography, computed tomography (CT), magnetic resonance imaging (MRI) and positron emission tomography (PET) have played an important role for accurate preoperative diagnostics, for the most part these techniques cannot be applied intraoperatively. Optical molecular imaging is a promising technique that provides a high degree of sensitivity and specificity in tumor margin detection. Furthermore, existing clinical applications have proven that optical molecular imaging is a powerful intraoperative tool for guiding surgeons performing precision procedures, thus enabling radical resection and improved survival rates. However, detection depth limitation exists in optical molecular imaging methods and further breakthroughs from optical to multi-modality intraoperative imaging methods are needed to develop more extensive and comprehensive intraoperative applications. Here, we review the current intraoperative optical molecular imaging technologies, focusing on contrast agents and surgical navigation systems, and then discuss the future prospects of multi-modality imaging technology for intraoperative imaging-guided cancer surgery.

Intraoperative Imaging-Guided Cancer Surgery: From Current Fluorescence Molecular Imaging Methods to Future Multi-Modality Imaging Technology

PubMed Central

Chi, Chongwei; Du, Yang; Ye, Jinzuo; Kou, Deqiang; Qiu, Jingdan; Wang, Jiandong; Tian, Jie; Chen, Xiaoyuan

2014-01-01

Cancer is a major threat to human health. Diagnosis and treatment using precision medicine is expected to be an effective method for preventing the initiation and progression of cancer. Although anatomical and functional imaging techniques such as radiography, computed tomography (CT), magnetic resonance imaging (MRI) and positron emission tomography (PET) have played an important role for accurate preoperative diagnostics, for the most part these techniques cannot be applied intraoperatively. Optical molecular imaging is a promising technique that provides a high degree of sensitivity and specificity in tumor margin detection. Furthermore, existing clinical applications have proven that optical molecular imaging is a powerful intraoperative tool for guiding surgeons performing precision procedures, thus enabling radical resection and improved survival rates. However, detection depth limitation exists in optical molecular imaging methods and further breakthroughs from optical to multi-modality intraoperative imaging methods are needed to develop more extensive and comprehensive intraoperative applications. Here, we review the current intraoperative optical molecular imaging technologies, focusing on contrast agents and surgical navigation systems, and then discuss the future prospects of multi-modality imaging technology for intraoperative imaging-guided cancer surgery. PMID:25250092

Molecular Imaging and Precision Medicine in Prostate Cancer.

PubMed

Ceci, Francesco; Fiorentino, Michelangelo; Castellucci, Paolo; Fanti, Stefano

2017-01-01

The aim of the present review is to discuss about the role of new probes for molecular imaging in the evaluation of prostate cancer (PCa). This review focuses particularly on the role of new promising radiotracers for the molecular imaging with PET/computed tomography in the detection of PCa recurrence. The role of these new imaging techniques to guide lesion-target therapies and the potential application of these molecular probes as theranostics agents is discussed. Finally, the molecular mechanisms underlying resistance to castration in PCa and the maintenance of active androgen receptor are discussed. Copyright © 2016 Elsevier Inc. All rights reserved.

Immuno-SPET/CT and immuno-PET/CT: a step ahead to translational imaging.

PubMed

Pecking, Alain P; Bellet, Dominique; Alberini, Jean Louis

2012-10-01

Malignant tumours have the remarkable property to express cell surface antigens. Pressman was first reporting that radiolabeled antibodies were capable of organ localization. It was a promising challenge but the expected success and the development of this imaging method was limited by a poor imaging resolution despite a rather good specificity of the antibodies used. Identification of key cell surface markers is opening a new era as potential molecular imaging biomarkers in oncologic applications. Antibodies production has been promoted by the development of engineered fragments with preserved immunological properties and pharmacokinetics optimized for molecular imaging. A good compromise has to be obtained between the biological properties of the antibody and the physical half-life of the radionuclide. Several positron emission tomography (PET) radionuclides such as iodine-124, copper-64, yttrium-86 or zirconium-89 have been the focus of recent immuno-PET studies with interesting informative images in preclinical and clinical studies. Thanks to the development of more sensitive new detectors and specific software, molecular imaging methods, particularly PET imaging, allow nowadays the detection of lesions smaller than 5 mm in human. Immuno-PET can potentially be used for tumour detection and identification at diagnosis, staging and restaging, for treatment selection and monitoring, and during follow-up. Moreover the availability of matched imaging or therapeutic radionuclide pairs, such as (124)I/(131)I, (64)Cu/(67)Cu and (86)Y/(90)Y, make easier the quantification of tissue uptake and dosimetry calculation for radioimmunotherapy.

75 FR 51277 - Center for Scientific Review; Notice of Closed Meetings

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-19

..., Genomes, and Genetics Integrated Review Group; Molecular Genetics B Study Section. Date: October 3-4, 2010... and Urological Systems Integrated Review Group; Clinical, Integrative and Molecular Gastroenterology... Integrated Review Group; Clinical Molecular Imaging and Probe Development. Date: October 4-5, 2010. Time: 7 p...

Applications of Molecular Imaging

PubMed Central

Galbán, Craig; Galbán, Stefanie; Van Dort, Marcian; Luker, Gary D.; Bhojani, Mahaveer S.; Rehemtualla, Alnawaz; Ross, Brian D.

2015-01-01

Today molecular imaging technologies play a central role in clinical oncology. The use of imaging techniques in early cancer detection, treatment response and new therapy development is steadily growing and has already significantly impacted clinical management of cancer. In this chapter we will overview three different molecular imaging technologies used for the understanding of disease biomarkers, drug development, or monitoring therapeutic outcome. They are (1) optical imaging (bioluminescence and fluorescence imaging) (2) magnetic resonance imaging (MRI), and (3) nuclear imaging (e.g, single photon emission computed tomography (SPECT) and positron emission tomography (PET)). We will review the use of molecular reporters of biological processes (e.g. apoptosis and protein kinase activity) for high throughput drug screening and new cancer therapies, diffusion MRI as a biomarker for early treatment response and PET and SPECT radioligands in oncology. PMID:21075334

Simultaneous in vivo imaging of melanin and lipofuscin in the retina with multimodal photoacoustic ophthalmoscopy

NASA Astrophysics Data System (ADS)

Zhang, Xiangyang; Zhang, Hao F.; Zhou, Lixiang; Jiao, Shuliang

2012-02-01

We combined photoacoustic ophthalmoscopy (PAOM) with autofluorescence imaging for simultaneous in vivo imaging of dual molecular contrasts in the retina using a single light source. The dual molecular contrasts come from melanin and lipofuscin in the retinal pigment epithelium (RPE). Melanin and lipofuscin are two types of pigments and are believed to play opposite roles (protective vs. exacerbate) in the RPE in the aging process. We successfully imaged the retina of pigmented and albino rats at different ages. The experimental results showed that multimodal PAOM system can be a potentially powerful tool in the study of age-related degenerative retinal diseases.

Molecular imaging in the framework of personalized cancer medicine.

PubMed

Belkić, Dzevad; Belkić, Karen

2013-11-01

With our increased understanding of cancer cell biology, molecular imaging offers a strategic bridge to oncology. This complements anatomic imaging, particularly magnetic resonance (MR) imaging, which is sensitive but not specific. Among the potential harms of false positive findings is lowered adherence to recommended surveillance post-therapy and by persons at increased cancer risk. Positron emission tomography (PET) plus computerized tomography (CT) is the molecular imaging modality most widely used in oncology. In up to 40% of cases, PET-CT leads to changes in therapeutic management. Newer PET tracers can detect tumor hypoxia, bone metastases in androgen-sensitive prostate cancer, and human epidermal growth factor receptor type 2 (HER2)-expressive tumors. Magnetic resonance spectroscopy provides insight into several metabolites at the same time. Combined with MRI, this yields magnetic resonance spectroscopic imaging (MRSI), which does not entail ionizing radiation and is thus suitable for repeated monitoring. Using advanced signal processing, quantitative information can be gleaned about molecular markers of brain, breast, prostate and other cancers. Radiation oncology has benefited from molecular imaging via PET-CT and MRSI. Advanced mathematical approaches can improve dose planning in stereotactic radiosurgery, stereotactic body radiotherapy and high dose-rate brachytherapy. Molecular imaging will likely impact profoundly on clinical decision making in oncology. Molecular imaging via MR could facilitate early detection especially in persons at high risk for specific cancers.

Nondestructive cryomicro-CT imaging enables structural and molecular analysis of human lung tissue.

PubMed

Vasilescu, Dragoş M; Phillion, André B; Tanabe, Naoya; Kinose, Daisuke; Paige, David F; Kantrowitz, Jacob J; Liu, Gang; Liu, Hanqiao; Fishbane, Nick; Verleden, Stijn E; Vanaudenaerde, Bart M; Lenburg, Marc; Stevenson, Christopher S; Spira, Avrum; Cooper, Joel D; Hackett, Tillie-Louise; Hogg, James C

2017-01-01

Micro-computed tomography (CT) enables three-dimensional (3D) imaging of complex soft tissue structures, but current protocols used to achieve this goal preclude cellular and molecular phenotyping of the tissue. Here we describe a radiolucent cryostage that permits micro-CT imaging of unfixed frozen human lung samples at an isotropic voxel size of (11 µm) 3 under conditions where the sample is maintained frozen at -30°C during imaging. The cryostage was tested for thermal stability to maintain samples frozen up to 8 h. This report describes the methods used to choose the materials required for cryostage construction and demonstrates that whole genome mRNA integrity and expression are not compromised by exposure to micro-CT radiation and that the tissue can be used for immunohistochemistry. The new cryostage provides a novel method enabling integration of 3D tissue structure with cellular and molecular analysis to facilitate the identification of molecular determinants of disease. The described micro-CT cryostage provides a novel way to study the three-dimensional lung structure preserved without the effects of fixatives while enabling subsequent studies of the cellular matrix composition and gene expression. This approach will, for the first time, enable researchers to study structural changes of lung tissues that occur with disease and correlate them with changes in gene or protein signatures. Copyright © 2017 the American Physiological Society.

Whole-Brain Microscopy Meets In Vivo Neuroimaging: Techniques, Benefits, and Limitations.

PubMed

Aswendt, Markus; Schwarz, Martin; Abdelmoula, Walid M; Dijkstra, Jouke; Dedeurwaerdere, Stefanie

2017-02-01

Magnetic resonance imaging, positron emission tomography, and optical imaging have emerged as key tools to understand brain function and neurological disorders in preclinical mouse models. They offer the unique advantage of monitoring individual structural and functional changes over time. What remained unsolved until recently was to generate whole-brain microscopy data which can be correlated to the 3D in vivo neuroimaging data. Conventional histological sections are inappropriate especially for neuronal tracing or the unbiased screening for molecular targets through the whole brain. As part of the European Society for Molecular Imaging (ESMI) meeting 2016 in Utrecht, the Netherlands, we addressed this issue in the Molecular Neuroimaging study group meeting. Presentations covered new brain clearing methods, light sheet microscopes for large samples, and automatic registration of microscopy to in vivo imaging data. In this article, we summarize the discussion; give an overview of the novel techniques; and discuss the practical needs, benefits, and limitations.

Molecular Imaging of Atherothrombotic Diseases: Seeing Is Believing.

PubMed

Wang, Xiaowei; Peter, Karlheinz

2017-06-01

Molecular imaging, with major advances in the development of both innovative targeted contrast agents/particles and radiotracers, as well as various imaging technologies, is a fascinating, rapidly growing field with many preclinical and clinical applications, particularly for personalized medicine. Thrombosis in either the venous or the arterial system, the latter typically caused by rupture of unstable atherosclerotic plaques, is a major determinant of mortality and morbidity in patients. However, imaging of the various thrombotic complications and the identification of plaques that are prone to rupture are at best indirect, mostly unreliable, or not available at all. The development of molecular imaging toward diagnosis and prevention of thrombotic disease holds promise for major advance in this clinically important field. Here, we review the medical need and clinical importance of direct molecular imaging of thrombi and unstable atherosclerotic plaques that are prone to rupture, thereby causing thrombotic complications such as myocardial infarction and ischemic stroke. We systematically compare the advantages/disadvantages of the various molecular imaging modalities, including X-ray computed tomography, magnetic resonance imaging, positron emission tomography, single-photon emission computed tomography, fluorescence imaging, and ultrasound. We further systematically discuss molecular targets specific for thrombi and those characterizing unstable, potentially thrombogenic atherosclerotic plaques. Finally, we provide examples for first theranostic approaches in thrombosis, combining diagnosis, targeted therapy, and monitoring of therapeutic success or failure. Overall, molecular imaging is a rapidly advancing field that holds promise of major benefits to many patients with atherothrombotic diseases. © 2017 American Heart Association, Inc.

Advances in molecular labeling, high throughput imaging and machine intelligence portend powerful functional cellular biochemistry tools.

PubMed

Price, Jeffrey H; Goodacre, Angela; Hahn, Klaus; Hodgson, Louis; Hunter, Edward A; Krajewski, Stanislaw; Murphy, Robert F; Rabinovich, Andrew; Reed, John C; Heynen, Susanne

2002-01-01

Cellular behavior is complex. Successfully understanding systems at ever-increasing complexity is fundamental to advances in modern science and unraveling the functional details of cellular behavior is no exception. We present a collection of prospectives to provide a glimpse of the techniques that will aid in collecting, managing and utilizing information on complex cellular processes via molecular imaging tools. These include: 1) visualizing intracellular protein activity with fluorescent markers, 2) high throughput (and automated) imaging of multilabeled cells in statistically significant numbers, and 3) machine intelligence to analyze subcellular image localization and pattern. Although not addressed here, the importance of combining cell-image-based information with detailed molecular structure and ligand-receptor binding models cannot be overlooked. Advanced molecular imaging techniques have the potential to impact cellular diagnostics for cancer screening, clinical correlations of tissue molecular patterns for cancer biology, and cellular molecular interactions for accelerating drug discovery. The goal of finally understanding all cellular components and behaviors will be achieved by advances in both instrumentation engineering (software and hardware) and molecular biochemistry. Copyright 2002 Wiley-Liss, Inc.

Inverse transport problems in quantitative PAT for molecular imaging

NASA Astrophysics Data System (ADS)

Ren, Kui; Zhang, Rongting; Zhong, Yimin

2015-12-01

Fluorescence photoacoustic tomography (fPAT) is a molecular imaging modality that combines photoacoustic tomography with fluorescence imaging to obtain high-resolution imaging of fluorescence distributions inside heterogeneous media. The objective of this work is to study inverse problems in the quantitative step of fPAT where we intend to reconstruct physical coefficients in a coupled system of radiative transport equations using internal data recovered from ultrasound measurements. We derive uniqueness and stability results on the inverse problems and develop some efficient algorithms for image reconstructions. Numerical simulations based on synthetic data are presented to validate the theoretical analysis. The results we present here complement these in Ren K and Zhao H (2013 SIAM J. Imaging Sci. 6 2024-49) on the same problem but in the diffusive regime.

Pulsed Magneto-motive Ultrasound Imaging Using Ultrasmall Magnetic Nanoprobes

PubMed Central

Mehrmohammadi, Mohammad; Oh, Junghwan; Mallidi, Srivalleesha; Emelianov, Stanislav Y.

2011-01-01

Nano-sized particles are widely regarded as a tool to study biologic events at the cellular and molecular levels. However, only some imaging modalities can visualize interaction between nanoparticles and living cells. We present a new technique, pulsed magneto-motive ultrasound imaging, which is capable of in vivo imaging of magnetic nanoparticles in real time and at sufficient depth. In pulsed magneto-motive ultrasound imaging, an external high-strength pulsed magnetic field is applied to induce the motion within the magnetically labeled tissue and ultrasound is used to detect the induced internal tissue motion. Our experiments demonstrated a sufficient contrast between normal and iron-laden cells labeled with ultrasmall magnetic nanoparticles. Therefore, pulsed magneto-motive ultrasound imaging could become an imaging tool capable of detecting magnetic nanoparticles and characterizing the cellular and molecular composition of deep-lying structures. PMID:21439255

The Graduate Training Programme "Molecular Imaging for the Analysis of Gene and Protein Expression": A Case Study with an Insight into the Participation of Universities of Applied Sciences

ERIC Educational Resources Information Center

Hafner, Mathias

2008-01-01

Cell biology and molecular imaging technologies have made enormous progress in basic research. However, the transfer of this knowledge to the pharmaceutical drug discovery process, or even therapeutic improvements for disorders such as neuronal diseases, is still in its infancy. This transfer needs scientists who can integrate basic research with…

Nanomorphology of P3HT:PCBM-based absorber layers of organic solar cells after different processing conditions analyzed by low-energy scanning transmission electron microscopy.

PubMed

Pfaff, Marina; Klein, Michael F G; Müller, Erich; Müller, Philipp; Colsmann, Alexander; Lemmer, Uli; Gerthsen, Dagmar

2012-12-01

In this study the nanomorphology of P3HT:PC61BM absorber layers of organic solar cells was studied as a function of the processing parameters and for P3HT with different molecular weight. For this purpose we apply scanning transmission electron microscopy (STEM) at low electron energies in a scanning electron microscope. This method exhibits sensitive material contrast in the high-angle annular dark-field (HAADF) mode, which is well suited to distinguish materials with similar densities and mean atomic numbers. The images taken with low-energy HAADF STEM are compared with conventional transmission electron microscopy and atomic force microscopy images to illustrate the capabilities of the different techniques. For the interpretation of the low-energy HAADF STEM images, a semiempirical equation is used to calculate the image intensities. The experiments show that the nanomorphology of the P3HT:PC61BM blends depends strongly on the molecular weight of the P3HT. Low-molecular-weight P3HT forms rod-like domains during annealing. In contrast, only small globular features are visible in samples containing high-molecular-weight P3HT, which do not change significantly after annealing at 150°C up to 30 min.

Quantitative image analysis of cellular heterogeneity in breast tumors complements genomic profiling.

PubMed

Yuan, Yinyin; Failmezger, Henrik; Rueda, Oscar M; Ali, H Raza; Gräf, Stefan; Chin, Suet-Feung; Schwarz, Roland F; Curtis, Christina; Dunning, Mark J; Bardwell, Helen; Johnson, Nicola; Doyle, Sarah; Turashvili, Gulisa; Provenzano, Elena; Aparicio, Sam; Caldas, Carlos; Markowetz, Florian

2012-10-24

Solid tumors are heterogeneous tissues composed of a mixture of cancer and normal cells, which complicates the interpretation of their molecular profiles. Furthermore, tissue architecture is generally not reflected in molecular assays, rendering this rich information underused. To address these challenges, we developed a computational approach based on standard hematoxylin and eosin-stained tissue sections and demonstrated its power in a discovery and validation cohort of 323 and 241 breast tumors, respectively. To deconvolute cellular heterogeneity and detect subtle genomic aberrations, we introduced an algorithm based on tumor cellularity to increase the comparability of copy number profiles between samples. We next devised a predictor for survival in estrogen receptor-negative breast cancer that integrated both image-based and gene expression analyses and significantly outperformed classifiers that use single data types, such as microarray expression signatures. Image processing also allowed us to describe and validate an independent prognostic factor based on quantitative analysis of spatial patterns between stromal cells, which are not detectable by molecular assays. Our quantitative, image-based method could benefit any large-scale cancer study by refining and complementing molecular assays of tumor samples.

Perspective: Advanced particle imaging

DOE PAGES

Chandler, David W.; Houston, Paul L.; Parker, David H.

2017-05-26

This study discuss, the first ion imaging experiment demonstrating the capability of collecting an image of the photofragments from a unimolecular dissociation event and analyzing that image to obtain the three-dimensional velocity distribution of the fragments, the efficacy and breadth of application of the ion imaging technique have continued to improve and grow. With the addition of velocity mapping, ion/electron centroiding, and slice imaging techniques, the versatility and velocity resolution have been unmatched. Recent improvements in molecular beam, laser, sensor, and computer technology are allowing even more advanced particle imaging experiments, and eventually we can expect multi-mass imaging with co-variancemore » and full coincidence capability on a single shot basis with repetition rates in the kilohertz range. This progress should further enable “complete” experiments—the holy grail of molecular dynamics—where all quantum numbers of reactants and products of a bimolecular scattering event are fully determined and even under our control.« less

Molecular brain imaging in the multimodality era

PubMed Central

Price, Julie C

2012-01-01

Multimodality molecular brain imaging encompasses in vivo visualization, evaluation, and measurement of cellular/molecular processes. Instrumentation and software developments over the past 30 years have fueled advancements in multimodality imaging platforms that enable acquisition of multiple complementary imaging outcomes by either combined sequential or simultaneous acquisition. This article provides a general overview of multimodality neuroimaging in the context of positron emission tomography as a molecular imaging tool and magnetic resonance imaging as a structural and functional imaging tool. Several image examples are provided and general challenges are discussed to exemplify complementary features of the modalities, as well as important strengths and weaknesses of combined assessments. Alzheimer's disease is highlighted, as this clinical area has been strongly impacted by multimodality neuroimaging findings that have improved understanding of the natural history of disease progression, early disease detection, and informed therapy evaluation. PMID:22434068

Activateable Imaging Probes Light Up Inside Cancer Cells | Center for Cancer Research

Cancer.gov

Imaging can be used to help diagnose cancer as well as monitor tumor progression and response to treatment. The field of molecular imaging focuses on techniques capable of detecting specific molecular targets associated with cancer; the agents used for molecular imaging—often called probes—are multifunctional, with components that allow them to both interact with their molecular target and emit a detectable signal.

Time-resolved molecular imaging

NASA Astrophysics Data System (ADS)

Xu, Junliang; Blaga, Cosmin I.; Agostini, Pierre; DiMauro, Louis F.

2016-06-01

Time-resolved molecular imaging is a frontier of ultrafast optical science and physical chemistry. In this article, we review present and future key spectroscopic and microscopic techniques for ultrafast imaging of molecular dynamics and show their differences and connections. The advent of femtosecond lasers and free electron x-ray lasers bring us closer to this goal, which eventually will extend our knowledge about molecular dynamics to the attosecond time domain.

Three-dimensional nanoscale molecular imaging by extreme ultraviolet laser ablation mass spectrometry

PubMed Central

Kuznetsov, Ilya; Filevich, Jorge; Dong, Feng; Woolston, Mark; Chao, Weilun; Anderson, Erik H.; Bernstein, Elliot R.; Crick, Dean C.; Rocca, Jorge J.; Menoni, Carmen S.

2015-01-01

Analytical probes capable of mapping molecular composition at the nanoscale are of critical importance to materials research, biology and medicine. Mass spectral imaging makes it possible to visualize the spatial organization of multiple molecular components at a sample's surface. However, it is challenging for mass spectral imaging to map molecular composition in three dimensions (3D) with submicron resolution. Here we describe a mass spectral imaging method that exploits the high 3D localization of absorbed extreme ultraviolet laser light and its fundamentally distinct interaction with matter to determine molecular composition from a volume as small as 50 zl in a single laser shot. Molecular imaging with a lateral resolution of 75 nm and a depth resolution of 20 nm is demonstrated. These results open opportunities to visualize chemical composition and chemical changes in 3D at the nanoscale. PMID:25903827

78 FR 56239 - Center for Scientific Review; Notice of Closed Meetings

Federal Register 2010, 2011, 2012, 2013, 2014

2013-09-12

... Integrated Review Group; Molecular and Cellular. Endocrinology Study Section Date: October 8, 2013. Time: 8... Molecular Sciences and Training Integrated Review Group; Enabling Bioanalytical and Imaging Technologies...: Genes, Genomes, and Genetics Integrated Review Group; Genetics of Health and Disease Study Section. Date...

Instrumentation in molecular imaging.

PubMed

Wells, R Glenn

2016-12-01

In vivo molecular imaging is a challenging task and no single type of imaging system provides an ideal solution. Nuclear medicine techniques like SPECT and PET provide excellent sensitivity but have poor spatial resolution. Optical imaging has excellent sensitivity and spatial resolution, but light photons interact strongly with tissues and so only small animals and targets near the surface can be accurately visualized. CT and MRI have exquisite spatial resolution, but greatly reduced sensitivity. To overcome the limitations of individual modalities, molecular imaging systems often combine individual cameras together, for example, merging nuclear medicine cameras with CT or MRI to allow the visualization of molecular processes with both high sensitivity and high spatial resolution.

Nonunique and nonuniform mapping in few-body Coulomb-explosion imaging

NASA Astrophysics Data System (ADS)

Sayler, A. M.; Eckner, E.; McKenna, J.; Esry, B. D.; Carnes, K. D.; Ben-Itzhak, I.; Paulus, G. G.

2018-03-01

Much of our knowledge of molecular geometry and interaction dynamics comes from indirect measurements of the molecular fragments following breakup. This technique—Coulomb-explosion imaging (CEI), i.e., determining the initial molecular configuration of a system from the momenta of the resulting fragments using knowledge of the particle interactions—is one of the fundamental tools of molecular physics. Moreover, CEI has been a staple of molecular studies for decades. Here we show that one often cannot assign a unique initial configuration to the few-body breakup of a polyatomic molecule given the measurement of the resulting fragments' momenta. Specifically, multiple initial configurations can result in identical momenta for a molecule breaking into three or more parts. Further, the nonunique and nonuniform mapping from the initial configuration to the measured momenta also significantly complicates the determination of molecular alignment at the time of breakup.

Molecular imaging in neuroendocrine tumors: molecular uptake mechanisms and clinical results.

PubMed

Koopmans, Klaas P; Neels, Oliver N; Kema, Ido P; Elsinga, Philip H; Links, Thera P; de Vries, Elisabeth G E; Jager, Pieter L

2009-09-01

Neuroendocrine tumors can originate almost everywhere in the body and consist of a great variety of subtypes. This paper focuses on molecular imaging methods using nuclear medicine techniques in neuroendocrine tumors, coupling molecular uptake mechanisms of radiotracers with clinical results. A non-systematic review is presented on receptor based and metabolic imaging methods. Receptor-based imaging covers the molecular backgrounds of somatostatin, vaso-intestinal peptide (VIP), bombesin and cholecystokinin (CCK) receptors and their link with nuclear imaging. Imaging methods based on specific metabolic properties include meta-iodo-benzylguanide (MIBG) and dimercapto-sulphuric acid (DMSA-V) scintigraphy as well as more modern positron emission tomography (PET)-based methods using radio-labeled analogues of amino acids, glucose, dihydroxyphenylalanine (DOPA), dopamine and tryptophan. Diagnostic sensitivities are presented for each imaging method and for each neuroendocrine tumor subtype. Finally, a Forest plot analysis of diagnostic performance is presented for each tumor type in order to provide a comprehensive overview for clinical use.

Breast Cancer Treatment in the Era of Molecular Imaging

PubMed Central

Edelhauser, Gundula; Funovics, Martin

2008-01-01

Summary Molecular imaging employs molecularly targeted probes to visualize and often quantify distinct disease-specific markers and pathways. Modalities like intravital confocal or multiphoton microscopy, near-infrared fluorescence combined with endoscopy, surface reflectance imaging, or fluorescence-mediated tomography, and radionuclide imaging with positron emission tomography (PET) and single-photon emission computed tomography (SPECT) are increasingly used for small animal high-throughput screening, drug development and testing, and monitoring gene therapy experiments. In the clinical treatment of breast cancer, PET and SPECT as well as magnetic resonance-based molecular imaging are already established for the staging of distant disease and intrathoracic nodal status, for patient selection regarding receptor-directed treatments, and to gain early information about treatment efficacy. In the near future, reporter gene imaging during gene therapy and further spatial and qualitative characterization of the disease can become clinically possible with radionuclide and optical methods. Ultimately, it may be expected that every level of breast cancer treatment will be affected by molecular imaging, including screening. PMID:21048912

Recent advances in targeted endoscopic imaging: Early detection of gastrointestinal neoplasms

PubMed Central

Kwon, Yong-Soo; Cho, Young-Seok; Yoon, Tae-Jong; Kim, Ho-Shik; Choi, Myung-Gyu

2012-01-01

Molecular imaging has emerged as a new discipline in gastrointestinal endoscopy. This technology encompasses modalities that can visualize disease-specific morphological or functional tissue changes based on the molecular signature of individual cells. Molecular imaging has several advantages including minimal damage to tissues, repetitive visualization, and utility for conducting quantitative analyses. Advancements in basic science coupled with endoscopy have made early detection of gastrointestinal cancer possible. Molecular imaging during gastrointestinal endoscopy requires the development of safe biomarkers and exogenous probes to detect molecular changes in cells with high specificity anda high signal-to-background ratio. Additionally, a high-resolution endoscope with an accurate wide-field viewing capability must be developed. Targeted endoscopic imaging is expected to improve early diagnosis and individual therapy of gastrointestinal cancer. PMID:22442742

Molecular Imaging and Contrast Agent Database (MICAD): evolution and progress.

PubMed

Chopra, Arvind; Shan, Liang; Eckelman, W C; Leung, Kam; Latterner, Martin; Bryant, Stephen H; Menkens, Anne

2012-02-01

The purpose of writing this review is to showcase the Molecular Imaging and Contrast Agent Database (MICAD; www.micad.nlm.nih.gov ) to students, researchers, and clinical investigators interested in the different aspects of molecular imaging. This database provides freely accessible, current, online scientific information regarding molecular imaging (MI) probes and contrast agents (CA) used for positron emission tomography, single-photon emission computed tomography, magnetic resonance imaging, X-ray/computed tomography, optical imaging and ultrasound imaging. Detailed information on >1,000 agents in MICAD is provided in a chapter format and can be accessed through PubMed. Lists containing >4,250 unique MI probes and CAs published in peer-reviewed journals and agents approved by the United States Food and Drug Administration as well as a comma separated values file summarizing all chapters in the database can be downloaded from the MICAD homepage. Users can search for agents in MICAD on the basis of imaging modality, source of signal/contrast, agent or target category, pre-clinical or clinical studies, and text words. Chapters in MICAD describe the chemical characteristics (structures linked to PubChem), the in vitro and in vivo activities, and other relevant information regarding an imaging agent. All references in the chapters have links to PubMed. A Supplemental Information Section in each chapter is available to share unpublished information regarding an agent. A Guest Author Program is available to facilitate rapid expansion of the database. Members of the imaging community registered with MICAD periodically receive an e-mail announcement (eAnnouncement) that lists new chapters uploaded to the database. Users of MICAD are encouraged to provide feedback, comments, or suggestions for further improvement of the database by writing to the editors at micad@nlm.nih.gov.

Molecular Imaging and Contrast Agent Database (MICAD): Evolution and Progress

PubMed Central

Chopra, Arvind; Shan, Liang; Eckelman, W. C.; Leung, Kam; Latterner, Martin; Bryant, Stephen H.; Menkens, Anne

2011-01-01

The purpose of writing this review is to showcase the Molecular Imaging and Contrast Agent Database (MICAD; www.micad.nlm.nih.gov) to students, researchers and clinical investigators interested in the different aspects of molecular imaging. This database provides freely accessible, current, online scientific information regarding molecular imaging (MI) probes and contrast agents (CA) used for positron emission tomography, single-photon emission computed tomography, magnetic resonance imaging, x-ray/computed tomography, optical imaging and ultrasound imaging. Detailed information on >1000 agents in MICAD is provided in a chapter format and can be accessed through PubMed. Lists containing >4250 unique MI probes and CAs published in peer-reviewed journals and agents approved by the United States Food and Drug Administration (FDA) as well as a CSV file summarizing all chapters in the database can be downloaded from the MICAD homepage. Users can search for agents in MICAD on the basis of imaging modality, source of signal/contrast, agent or target category, preclinical or clinical studies, and text words. Chapters in MICAD describe the chemical characteristics (structures linked to PubChem), the in vitro and in vivo activities and other relevant information regarding an imaging agent. All references in the chapters have links to PubMed. A Supplemental Information Section in each chapter is available to share unpublished information regarding an agent. A Guest Author Program is available to facilitate rapid expansion of the database. Members of the imaging community registered with MICAD periodically receive an e-mail announcement (eAnnouncement) that lists new chapters uploaded to the database. Users of MICAD are encouraged to provide feedback, comments or suggestions for further improvement of the database by writing to the editors at: micad@nlm.nih.gov PMID:21989943

Phage display and molecular imaging: expanding fields of vision in living subjects.

PubMed

Cochran, R; Cochran, Frank

2010-01-01

In vivo molecular imaging enables non-invasive visualization of biological processes within living subjects, and holds great promise for diagnosis and monitoring of disease. The ability to create new agents that bind to molecular targets and deliver imaging probes to desired locations in the body is critically important to further advance this field. To address this need, phage display, an established technology for the discovery and development of novel binding agents, is increasingly becoming a key component of many molecular imaging research programs. This review discusses the expanding role played by phage display in the field of molecular imaging with a focus on in vivo applications. Furthermore, new methodological advances in phage display that can be directly applied to the discovery and development of molecular imaging agents are described. Various phage library selection strategies are summarized and compared, including selections against purified target, intact cells, and ex vivo tissue, plus in vivo homing strategies. An outline of the process for converting polypeptides obtained from phage display library selections into successful in vivo imaging agents is provided, including strategies to optimize in vivo performance. Additionally, the use of phage particles as imaging agents is also described. In the latter part of the review, a survey of phage-derived in vivo imaging agents is presented, and important recent examples are highlighted. Other imaging applications are also discussed, such as the development of peptide tags for site-specific protein labeling and the use of phage as delivery agents for reporter genes. The review concludes with a discussion of how phage display technology will continue to impact both basic science and clinical applications in the field of molecular imaging.

Multimodality Molecular Imaging-Guided Tumor Border Delineation and Photothermal Therapy Analysis Based on Graphene Oxide-Conjugated Gold Nanoparticles Chelated with Gd.

PubMed

Ma, Xibo; Jin, Yushen; Wang, Yi; Zhang, Shuai; Peng, Dong; Yang, Xin; Wei, Shoushui; Chai, Wei; Li, Xuejun; Tian, Jie

2018-01-01

Tumor cell complete extinction is a crucial measure to evaluate antitumor efficacy. The difficulties in defining tumor margins and finding satellite metastases are the reason for tumor recurrence. A synergistic method based on multimodality molecular imaging needs to be developed so as to achieve the complete extinction of the tumor cells. In this study, graphene oxide conjugated with gold nanostars and chelated with Gd through 1,4,7,10-tetraazacyclododecane-N,N',N,N'-tetraacetic acid (DOTA) (GO-AuNS-DOTA-Gd) were prepared to target HCC-LM3-fLuc cells and used for therapy. For subcutaneous tumor, multimodality molecular imaging including photoacoustic imaging (PAI) and magnetic resonance imaging (MRI) and the related processing techniques were used to monitor the pharmacokinetics process of GO-AuNS-DOTA-Gd in order to determine the optimal time for treatment. For orthotopic tumor, MRI was used to delineate the tumor location and margin in vivo before treatment. Then handheld photoacoustic imaging system was used to determine the tumor location during the surgery and guided the photothermal therapy. The experiment result based on orthotopic tumor demonstrated that this synergistic method could effectively reduce tumor residual and satellite metastases by 85.71% compared with the routine photothermal method without handheld PAI guidance. These results indicate that this multimodality molecular imaging-guided photothermal therapy method is promising with a good prospect in clinical application.

Facilitating in vivo tumor localization by principal component analysis based on dynamic fluorescence molecular imaging

NASA Astrophysics Data System (ADS)

Gao, Yang; Chen, Maomao; Wu, Junyu; Zhou, Yuan; Cai, Chuangjian; Wang, Daliang; Luo, Jianwen

2017-09-01

Fluorescence molecular imaging has been used to target tumors in mice with xenograft tumors. However, tumor imaging is largely distorted by the aggregation of fluorescent probes in the liver. A principal component analysis (PCA)-based strategy was applied on the in vivo dynamic fluorescence imaging results of three mice with xenograft tumors to facilitate tumor imaging, with the help of a tumor-specific fluorescent probe. Tumor-relevant features were extracted from the original images by PCA and represented by the principal component (PC) maps. The second principal component (PC2) map represented the tumor-related features, and the first principal component (PC1) map retained the original pharmacokinetic profiles, especially of the liver. The distribution patterns of the PC2 map of the tumor-bearing mice were in good agreement with the actual tumor location. The tumor-to-liver ratio and contrast-to-noise ratio were significantly higher on the PC2 map than on the original images, thus distinguishing the tumor from its nearby fluorescence noise of liver. The results suggest that the PC2 map could serve as a bioimaging marker to facilitate in vivo tumor localization, and dynamic fluorescence molecular imaging with PCA could be a valuable tool for future studies of in vivo tumor metabolism and progression.

Molecular Targeted Viral Nanoparticles as Tools for Imaging Cancer

PubMed Central

Cho, C.F.; Sourabh, S.; Simpson, E.J.; Steinmetz, N.F.; Luyt, L.G.; Lewis, J.D.

2015-01-01

Viral nanoparticles (VNPs) are a novel class of bionanomaterials that harness the natural biocompatibility of viruses for the development of therapeutics, vaccines, and imaging tools. The plant virus, cowpea mosaic virus (CPMV), has been successfully engineered to create novel cancer-targeted imaging agents by incorporating fluorescent dyes, polyethylene glycol (PEG) polymers, and targeting moieties. Using straightforward conjugation strategies, VNPs with high selectivity for cancer-specific molecular targets can be synthesized for in vivo imaging of tumors. Here we describe the synthesis and purification of CPMV-based VNPs, the functionalization of these VNPs using click chemistry, and their use for imaging xenograft tumors in animal models. VNPs decorated with fluorescent dyes, PEG, and targeting ligands can be synthesized in one day, and imaging studies can be performed over hours, days, or weeks, depending on the application. PMID:24243252

Synthesis and evaluation of novel Tc-99m labeled NGR-containing hexapeptides as tumor imaging agents.

PubMed

Kim, Dae-Weung; Kim, Woo Hyoung; Kim, Myoung Hyoun; Kim, Chang Guhn

2015-02-01

Asparagine-glycine-arginine (NGR)-containing peptides targeting aminopeptidase N (APN)/CD13 can be an excellent candidate for targeting ligands in molecular tumor imaging. In this study, we developed two NGR-containing hexapeptides, and evaluated the diagnostic performance of Tc-99m labeled hexapeptides as molecular imaging agents in an HT-1080 fibrosarcoma-bearing murine model. Peptides were synthesized using Fmoc solid-phase peptide synthesis. Radiochemical purity of Tc-99m was evaluated using instant thin-layer chromatography. The uptake of two NGR-containing hexapeptides within HT-1080 cells was evaluated in vitro. In HT-1080 fibrosarcoma tumor-bearing mice, gamma images were acquired. A biodistribution study was performed to calculate percentage of the injected dose per gram of tissue (%ID/g). Two hexapeptides, glutamic acid-cysteine-glycine (ECG)-NGR and NGR-ECG were successfully synthesized. After radiolabeling procedures with Tc-99m, the complexes Tc-99m hexapeptides were prepared in high yield. The uptake of Tc-99m ECG-NGR within the tumor cells had been assured by in vitro studies. The gamma camera imaging in the murine model showed that Tc-99m ECG-NGR was accumulated substantially in the subcutaneously engrafted tumor. However, Tc-99m NGR-ECG was accumulated minimally in the tumor. Two NGR-containing hexapeptides, ECG-NGR and NGR-ECG were developed as molecular imaging agents to target APN/CD13 in HT-1080 fibrosarcoma. Tc-99m ECG-NGR showed a significant uptake in the tumor, and it is a good candidate for tumor imaging. Copyright © 2015 John Wiley & Sons, Ltd.

Imaging Virus-Associated Cancer

PubMed Central

Fu, De-Xue; Foss, Catherine A.; Nimmagadda, Sridhar; Ambinder, Richard F.; Pomper, Martin G.

2012-01-01

Cancer remains an important and growing health problem. Researchers have made great progress in defining genetic and molecular alterations that contribute to cancer formation and progression. Molecular imaging can identify appropriate patients for targeted cancer therapy and may detect early biochemical changes in tumors during therapy, some of which may have important prognostic implications. Progress in this field continues largely due to a union between molecular genetics and advanced imaging technology. This review details uses of molecular-genetic imaging in the context of tumor-associated viruses. Under certain conditions, and particularly during pharmacologic stimulation, gammaherpesviruses will express genes that enable imaging and therapy in vivo. The techniques discussed are readily translatable to the clinic. PMID:18991718

EDITORIAL: Molecular Imaging Technology

NASA Astrophysics Data System (ADS)

Asai, Keisuke; Okamoto, Koji

2006-06-01

'Molecular Imaging Technology' focuses on image-based techniques using nanoscale molecules as sensor probes to measure spatial variations of various species (molecular oxygen, singlet oxygen, carbon dioxide, nitric monoxide, etc) and physical properties (pressure, temperature, skin friction, velocity, mechanical stress, etc). This special feature, starting on page 1237, contains selected papers from The International Workshop on Molecular Imaging for Interdisciplinary Research, sponsored by the Ministry of Education, Culture, Sports, Science and Technology (MEXT) in Japan, which was held at the Sendai Mediatheque, Sendai, Japan, on 8 9 November 2004. The workshop was held as a sequel to the MOSAIC International Workshop that was held in Tokyo in 2003, to summarize the outcome of the 'MOSAIC Project', a five-year interdisciplinary project supported by Techno-Infrastructure Program, the Special Coordination Fund for Promotion of Science Technology to develop molecular sensor technology for aero-thermodynamic research. The workshop focused on molecular imaging technology and its applications to interdisciplinary research areas. More than 110 people attended this workshop from various research fields such as aerospace engineering, automotive engineering, radiotechnology, fluid dynamics, bio-science/engineering and medical engineering. The purpose of this workshop is to stimulate intermixing of these interdisciplinary fields for further development of molecular sensor and imaging technology. It is our pleasure to publish the seven papers selected from our workshop as a special feature in Measurement and Science Technology. We will be happy if this issue inspires people to explore the future direction of molecular imaging technology for interdisciplinary research.

Clinically Approved Nanoparticle Imaging Agents

PubMed Central

Thakor, Avnesh S.; Jokerst, Jesse V.; Ghanouni, Pejman; Campbell, Jos L.; Mittra, Erik

2016-01-01

Nanoparticles are a new class of imaging agent used for both anatomic and molecular imaging. Nanoparticle-based imaging exploits the signal intensity, stability, and biodistribution behavior of submicron-diameter molecular imaging agents. This review focuses on nanoparticles used in human medical imaging, with an emphasis on radionuclide imaging and MRI. Newer nanoparticle platforms are also discussed in relation to theranostic and multimodal uses. PMID:27738007

Online molecular image repository and analysis system: A multicenter collaborative open-source infrastructure for molecular imaging research and application.

PubMed

Rahman, Mahabubur; Watabe, Hiroshi

2018-05-01

Molecular imaging serves as an important tool for researchers and clinicians to visualize and investigate complex biochemical phenomena using specialized instruments; these instruments are either used individually or in combination with targeted imaging agents to obtain images related to specific diseases with high sensitivity, specificity, and signal-to-noise ratios. However, molecular imaging, which is a multidisciplinary research field, faces several challenges, including the integration of imaging informatics with bioinformatics and medical informatics, requirement of reliable and robust image analysis algorithms, effective quality control of imaging facilities, and those related to individualized disease mapping, data sharing, software architecture, and knowledge management. As a cost-effective and open-source approach to address these challenges related to molecular imaging, we develop a flexible, transparent, and secure infrastructure, named MIRA, which stands for Molecular Imaging Repository and Analysis, primarily using the Python programming language, and a MySQL relational database system deployed on a Linux server. MIRA is designed with a centralized image archiving infrastructure and information database so that a multicenter collaborative informatics platform can be built. The capability of dealing with metadata, image file format normalization, and storing and viewing different types of documents and multimedia files make MIRA considerably flexible. With features like logging, auditing, commenting, sharing, and searching, MIRA is useful as an Electronic Laboratory Notebook for effective knowledge management. In addition, the centralized approach for MIRA facilitates on-the-fly access to all its features remotely through any web browser. Furthermore, the open-source approach provides the opportunity for sustainable continued development. MIRA offers an infrastructure that can be used as cross-boundary collaborative MI research platform for the rapid achievement in cancer diagnosis and therapeutics. Copyright © 2018 Elsevier Ltd. All rights reserved.

The pivotal role of multimodality reporter sensors in drug discovery: from cell based assays to real time molecular imaging.

PubMed

Ray, Pritha

2011-04-01

Development and marketing of new drugs require stringent validation that are expensive and time consuming. Non-invasive multimodality molecular imaging using reporter genes holds great potential to expedite these processes at reduced cost. New generations of smarter molecular imaging strategies such as Split reporter, Bioluminescence resonance energy transfer, Multimodality fusion reporter technologies will further assist to streamline and shorten the drug discovery and developmental process. This review illustrates the importance and potential of molecular imaging using multimodality reporter genes in drug development at preclinical phases.

Piezoelectric Composite Micromachined Multifrequency Transducers for High-Resolution, High-Contrast Ultrasound Imaging for Improved Prostate Cancer Assessment

DTIC Science & Technology

2014-08-01

and in (b) a standard animal model of prostate cancer. In the preliminary in-vitro study , imaging resolution, contrast to tissue ratio, and lesion...detectability will be assessed relative to a Siemens EV- 8C4 transrectal ultrasound probe. In the in-vivo study , molecular imaging and microvascular...lesions will be imaged at several axial depths using our prototype array and the Siemens EV-8C4 clinical TRUS probe. A blinded reader study will be

How Imaging Can Impact Clinical Trial Design: Molecular Imaging as a Biomarker for Targeted Cancer Therapy.

PubMed

Mankoff, David A; Farwell, Michael D; Clark, Amy S; Pryma, Daniel A

2015-01-01

The ability to measure biochemical and molecular processes to guide cancer treatment represents a potentially powerful tool for trials of targeted cancer therapy. These assays have traditionally been performed by analysis of tissue samples. However, more recently, functional and molecular imaging has been developed that is capable of in vivo assays of cancer biochemistry and molecular biology and is highly complementary to tissue-based assays. Cancer imaging biomarkers can play a key role in increasing the efficacy and efficiency of therapeutic clinical trials and also provide insight into the biologic mechanisms that bring about a therapeutic response. Future progress will depend on close collaboration between imaging scientists and cancer physicians and on public and commercial sponsors, to take full advantage of what imaging has to offer for clinical trials of targeted cancer therapy. This review will provide examples of how molecular imaging can inform targeted cancer clinical trials and clinical decision making by (1) measuring regional expression of the therapeutic target, (2) assessing early (pharmacodynamic) response to treatment, and (3) predicting therapeutic outcome. The review includes a discussion of basic principles of molecular imaging biomarkers in cancer, with an emphasis on those methods that have been tested in patients. We then review clinical trials designed to evaluate imaging tests as integrated markers embedded in a therapeutic clinical trial with the goal of validating the imaging tests as integral markers that can aid patient selection and direct response-adapted treatment strategies. Examples of recently completed multicenter trials using imaging biomarkers are highlighted.

Synthesis and Biological Evaluation of Cyclic [99mTc]-HYNIC-CGPRPPC as a Fibrin-Binding Peptide for Molecular Imaging of Thrombosis and Its Comparison with [99mTc]-HYNIC-GPRPP.

PubMed

Rezaeianpour, Sedigheh; Bozorgi, Atefeh Hajiagha; Moghimi, Abolghasem; Almasi, Ameneh; Balalaie, Saeed; Ramezanpour, Sorour; Nasoohi, Sanaz; Mazidi, Seyed Mohammad; Geramifar, Parham; Bitarafan-Rajabi, Ahmad; Shahhosseini, Soraya

2017-04-01

Many patients worldwide suffer from cardiovascular diseases for which an underlying factor is thrombosis. Devising a molecular imaging technique for early detection of thrombosis in a clinical setting is highly recommended. Because fibrin is a major constituent of clots and is present in all types of thrombi but absent in circulation, it is a highly specific and sensitive target for molecular imaging of thrombi. It is assumed that cyclization of peptides will improve the receptor binding affinity and stability of the peptide. In the present study, we have developed linear and cyclic fibrin-binding peptides for thrombus imaging and compared their biological properties. Linear HYNIC-GPRPP and cyclic HYNIC-CGPRPPC peptides were synthesized using a standard Fmoc strategy and radiolabeled with Tc-99m. The stability of the radiolabeled peptides in human plasma and their affinity for fibrin and blood clots were determined. Blood clearance and biodistribution were evaluated in rats and mice, respectively. The peptide with the highest affinity was injected to a live rabbit femoral thrombosis model, and scintigraphic images were obtained. In vitro studies show that peptides are stable in human plasma and have a high affinity for human fibrin. They also demonstrated fast blood clearance in rats and high thrombus uptake in the Balb/c mice femoral thrombosis model. Femoral thrombosis was visualized 30 min postinjection of cyclic peptide in a live rabbit model using single photon emission computed tomography (SPECT)/X-ray computed tomography. The results indicate that the cyclic peptide is a promising agent for molecular imaging of fibrin using SPECT.

Next Generation Molecular Histology Using Highly Multiplexed Ion Beam Imaging (MIBI) of Breast Cancer Tissue Specimens for Enhanced Clinical Guidance

DTIC Science & Technology

2016-07-01

AWARD NUMBER: W81XWH- 14-1-0192 TITLE: Next-Generation Molecular Histology Using Highly Multiplexed Ion Beam Imaging (MIBI) of Breast Cancer...DATES COVERED 4. TITLE AND SUBTITLE Next-Generation Molecular Histology Using Highly Multiplexed Ion Beam Imaging (MIBI) of Breast Cancer Tissue

Molecular aspects of magnetic resonance imaging and spectroscopy.

PubMed

Boesch, C

1999-01-01

Magnetic resonance imaging (MRI) is a well known diagnostic tool in radiology that produces unsurpassed images of the human body, in particular of soft tissue. However, the medical community is often not aware that MRI is an important yet limited segment of magnetic resonance (MR) or nuclear magnetic resonance (NMR) as this method is called in basic science. The tremendous morphological information of MR images sometimes conceal the fact that MR signals in general contain much more information, especially on processes on the molecular level. NMR is successfully used in physics, chemistry, and biology to explore and characterize chemical reactions, molecular conformations, biochemical pathways, solid state material, and many other applications that elucidate invisible characteristics of matter and tissue. In medical applications, knowledge of the molecular background of MRI and in particular MR spectroscopy (MRS) is an inevitable basis to understand molecular phenomenon leading to macroscopic effects visible in diagnostic images or spectra. This review shall provide the necessary background to comprehend molecular aspects of magnetic resonance applications in medicine. An introduction into the physical basics aims at an understanding of some of the molecular mechanisms without extended mathematical treatment. The MR typical terminology is explained such that reading of original MR publications could be facilitated for non-MR experts. Applications in MRI and MRS are intended to illustrate the consequences of molecular effects on images and spectra.

Aptamer-Targeted Gold Nanoparticles As Molecular-Specific Contrast Agents for Reflectance Imaging

PubMed Central

2008-01-01

Targeted metallic nanoparticles have shown potential as a platform for development of molecular-specific contrast agents. Aptamers have recently been demonstrated as ideal candidates for molecular targeting applications. In this study, we investigated the development of aptamer-based gold nanoparticles as contrast agents, using aptamers as targeting agents and gold nanoparticles as imaging agents. We devised a novel conjugation approach using an extended aptamer design where the extension is complementary to an oligonucleotide sequence attached to the surface of the gold nanoparticles. The chemical and optical properties of the aptamer−gold conjugates were characterized using size measurements and oligonucleotide quantitation assays. We demonstrate this conjugation approach to create a contrast agent designed for detection of prostate-specific membrane antigen (PSMA), obtaining reflectance images of PSMA(+) and PSMA(−) cell lines treated with the anti-PSMA aptamer−gold conjugates. This design strategy can easily be modified to incorporate multifunctional agents as part of a multimodal platform for reflectance imaging applications. PMID:18512972

MRI of chemical reactions and processes.

PubMed

Britton, Melanie M

2017-08-01

As magnetic resonance imaging (MRI) can spatially resolve a wealth of molecular information available from nuclear magnetic resonance (NMR), it is able to non-invasively visualise the composition, properties and reactions of a broad range of spatially-heterogeneous molecular systems. Hence, MRI is increasingly finding applications in the study of chemical reactions and processes in a diverse range of environments and technologies. This article will explain the basic principles of MRI and how it can be used to visualise chemical composition and molecular properties, providing an overview of the variety of information available. Examples are drawn from the disciplines of chemistry, chemical engineering, environmental science, physics, electrochemistry and materials science. The review introduces a range of techniques used to produce image contrast, along with the chemical and molecular insight accessible through them. Methods for mapping the distribution of chemical species, using chemical shift imaging or spatially-resolved spectroscopy, are reviewed, as well as methods for visualising physical state, temperature, current density, flow velocities and molecular diffusion. Strategies for imaging materials with low signal intensity, such as those containing gases or low sensitivity nuclei, using compressed sensing, para-hydrogen or polarisation transfer, are discussed. Systems are presented which encapsulate the diversity of chemical and physical parameters observable by MRI, including one- and two-phase flow in porous media, chemical pattern formation, phase transformations and hydrodynamic (fingering) instabilities. Lastly, the emerging area of electrochemical MRI is discussed, with studies presented on the visualisation of electrochemical deposition and dissolution processes during corrosion and the operation of batteries, supercapacitors and fuel cells. Crown Copyright © 2017. Published by Elsevier B.V. All rights reserved.

Ferritin heavy chain as a molecular imaging reporter gene in glioma xenografts.

PubMed

Cheng, Sen; Mi, Ruifang; Xu, Yu; Jin, Guishan; Zhang, Junwen; Zhou, Yiqiang; Chen, Zhengguang; Liu, Fusheng

2017-06-01

The development of glioma therapy in clinical practice (e.g., gene therapy) calls for efficiently visualizing and tracking glioma cells in vivo. Human ferritin heavy chain is a novel gene reporter in magnetic resonance imaging. This study proposes hFTH as a reporter gene for MR molecular imaging in glioma xenografts. Rat C6 glioma cells were infected by packaged lentivirus carrying hFTH and EGFP genes and obtained by fluorescence-activated cell sorting. The iron-loaded ability was analyzed by the total iron reagent kit. Glioma nude mouse models were established subcutaneously and intracranially. Then, in vivo tumor bioluminescence was performed via the IVIS spectrum imaging system. The MR imaging analysis was analyzed on a 7T animal MRI scanner. Finally, the expression of hFTH was analyzed by western blotting and histological analysis. Stable glioma cells carrying hFTH and EGFP reporter genes were successfully obtained. The intracellular iron concentration was increased without impairing the cell proliferation rate. Glioma cells overexpressing hFTH showed significantly decreased signal intensity on T 2 -weighted MRI both in vitro and in vivo. EGFP fluorescent imaging could also be detected in the subcutaneous and intracranial glioma xenografts. Moreover, the expression of the transferritin receptor was significantly increased in glioma cells carrying the hFTH reporter gene. Our study illustrated that hFTH generated cellular MR imaging contrast efficiently in glioma via regulating the expression of transferritin receptor. This might be a useful reporter gene in cell tracking and MR molecular imaging for glioma diagnosis, gene therapy and tumor metastasis.

Four dimensional optoacoustic imaging of perfusion in preclinical breast tumor model in vivo (Conference Presentation)

NASA Astrophysics Data System (ADS)

Deán-Ben, Xosé Luís.; Ermolayev, Vladimir; Mandal, Subhamoy; Ntziachristos, Vasilis; Razansky, Daniel

2016-03-01

Imaging plays an increasingly important role in clinical management and preclinical studies of cancer. Application of optical molecular imaging technologies, in combination with highly specific contrast agent approaches, eminently contributed to understanding of functional and histological properties of tumors and anticancer therapies. Yet, optical imaging exhibits deterioration in spatial resolution and other performance metrics due to light scattering in deep living tissues. High resolution molecular imaging at the whole-organ or whole-body scale may therefore bring additional understanding of vascular networks, blood perfusion and microenvironment gradients of malignancies. In this work, we constructed a volumetric multispectral optoacoustic tomography (vMSOT) scanner for cancer imaging in preclinical models and explored its capacity for real-time 3D intravital imaging of whole breast cancer allografts in mice. Intrinsic tissue properties, such as blood oxygenation gradients, along with the distribution of externally administered liposomes carrying clinically-approved indocyanine green dye (lipo-ICG) were visualized in order to study vascularization, probe penetration and extravasation kinetics in different regions of interest within solid tumors. The use of v-MSOT along with the application of volumetric image analysis and perfusion tracking tools for studies of pathophysiological processes within microenvironment gradients of solid tumors demonstrated superior volumetric imaging system performance with sustained competitive resolution and imaging depth suitable for investigations in preclinical cancer models.

Experimental validation of L-shell x-ray fluorescence computed tomography imaging: phantom study

PubMed Central

Bazalova-Carter, Magdalena; Ahmad, Moiz; Xing, Lei; Fahrig, Rebecca

2015-01-01

Abstract. Thanks to the current advances in nanoscience, molecular biochemistry, and x-ray detector technology, x-ray fluorescence computed tomography (XFCT) has been considered for molecular imaging of probes containing high atomic number elements, such as gold nanoparticles. The commonly used XFCT imaging performed with K-shell x rays appears to have insufficient imaging sensitivity to detect the low gold concentrations observed in small animal studies. Low energy fluorescence L-shell x rays have exhibited higher signal-to-background ratio and appeared as a promising XFCT mode with greatly enhanced sensitivity. The aim of this work was to experimentally demonstrate the feasibility of L-shell XFCT imaging and to assess its achievable sensitivity. We built an experimental L-shell XFCT imaging system consisting of a miniature x-ray tube and two spectrometers, a silicon drift detector (SDD), and a CdTe detector placed at ±120  deg with respect to the excitation beam. We imaged a 28-mm-diameter water phantom with 4-mm-diameter Eppendorf tubes containing gold solutions with concentrations of 0.06 to 0.1% Au. While all Au vials were detectable in the SDD L-shell XFCT image, none of the vials were visible in the CdTe L-shell XFCT image. The detectability limit of the presented L-shell XFCT SDD imaging setup was 0.007% Au, a concentration observed in small animal studies. PMID:26839910

The Potential of Metabolic Imaging

PubMed Central

Di Gialleonardo, Valentina; Wilson, David M.; Keshari, Kayvan R.

2015-01-01

Metabolic imaging is a field of molecular imaging that focuses and targets changes in metabolic pathways for the evaluation of different clinical conditions. Targeting and quantifying metabolic changes non-invasively is a powerful approach to facilitate diagnosis and evaluate therapeutic response. This review addresses only techniques targeting metabolic pathways. Other molecular imaging strategies, such as affinity/receptor imaging or microenvironment-dependent methods are beyond the scope of this review. Here we describe the current state of the art in clinically translatable metabolic imaging modalities. Specifically, we will focus on positron emission tomography (PET) and magnetic resonance spectroscopy (MRS), including conventional 1H and 13C MRS at thermal equilibrium and hyperpolarized magnetic resonance imaging (HP MRI). In this paper, we first provide an overview of metabolic pathways that are altered in many pathological conditions and the corresponding probes and techniques used to study those alterations. We will then describe the application of metabolic imaging to several common diseases including cancer, neurodegeneration, cardiac ischemia, and infection/inflammation. PMID:26687855

A rational regulatory approach for positron emission tomography imaging probes: from "first in man" to NDA approval and reimbursement.

PubMed

Barrio, Jorge R; Marcus, Carol S; Hung, Joseph C; Keppler, Jennifer S

2004-01-01

We propose a new regulatory approach for positron emission tomography (PET) molecular imaging probes, essential tools in today's medicine. Even though the focus of this paper is on positron-emitting labeled probes, it is also justified to extend this proposed regulatory approach to other diagnostic nuclear medicine radiopharmaceuticals. Key aspects of this proposal include: (1) PET molecular imaging probes would be placed in a "no significant risk" category, similar to that category for devices in current Food and Drug Administration (FDA) regulations, based on overwhelming scientific evidence that demonstrates their faultless safety profile; (2) the FDA-sanctioned Radioactive Drug Research Committee (RDRC) will oversee all diagnostic research with these probes. The newly defined RDRC should approve "first in man" use; supervise a broader spectrum of diagnostic research protocols, including those looking to demonstrate initial efficacy, as well as multicenter clinical trials and the use of molecular imaging probes as a screening tool in drug discovery. The current investigational new drug (IND) mechanism is thus eliminated for these diagnostic probes; (3) when a molecular imaging probe has demonstrated diagnostic efficacy, FDA approval (i.e., NDA) will be sought. The review will be done by a newly constituted Radioactive Drug Advisory Committee (RDAC) composed of experts chosen by the professional societies, who would provide a binding assessment of the adequacy of the safety and efficacy data. When the RDAC recommends its diagnostic use on scientific and medical grounds, the molecular imaging probe becomes FDA approved. After a molecular imaging probe is approved for a diagnostic indication, the existing mechanism to seek reimbursement will be utilized; and (4) the FDA would retain its direct oversight function for traditional manufacturers engaged in commercial distribution of the approved diagnostic molecular imaging probes (i.e., under NDA) to monitor compliance with existing US Pharmacopeia (USP) requirements. With abbreviated and more appropriate regulations, new PET molecular imaging probes for diagnostic use would be then rapidly incorporated into the mainstream diagnostic medicine. Equally importantly, this approach would facilitate the use of molecular imaging in drug discovery and development, which would substantially reduce the costs and time required to bring new therapeutic drugs to market.

Atomic resolution ADF-STEM imaging of organic molecular crystal of halogenated copper phthalocyanine.

PubMed

Haruta, Mitsutaka; Yoshida, Kaname; Kurata, Hiroki; Isoda, Seiji

2008-05-01

Annular dark-field (ADF) scanning transmission electron microscopy (STEM) measurements are demonstrated for the first time to be applicable for acquiring Z-contrast images of organic molecules at atomic resolution. High-angle ADF imaging by STEM is a new technique that provides incoherent high-resolution Z-contrast images for organic molecules. In the present study, low-angle ADF-STEM is successfully employed to image the molecular crystal structure of hexadecachloro-Cu-phthalocyanine (Cl16-CuPc), an organic molecule. The structures of CuPc derivatives (polyhalogenated CuPc with Br and Cl) are determined quantitatively using the same technique to determine the occupancy of halogens at each chemical site. By comparing the image contrasts of atomic columns, the occupancy of Br is found to be ca. 56% at the inner position, slightly higher than that for random substitution and in good agreement with previous TEM results.

Molecular Imaging of Apoptosis: From Micro to Macro

PubMed Central

Zeng, Wenbin; Wang, Xiaobo; Xu, Pengfei; Liu, Gang; Eden, Henry S.; Chen, Xiaoyuan

2015-01-01

Apoptosis, or programmed cell death, is involved in numerous human conditions including neurodegenerative diseases, ischemic damage, autoimmune disorders and many types of cancer, and is often confused with other types of cell death. Therefore strategies that enable visualized detection of apoptosis would be of enormous benefit in the clinic for diagnosis, patient management, and development of new therapies. In recent years, improved understanding of the apoptotic machinery and progress in imaging modalities have provided opportunities for researchers to formulate microscopic and macroscopic imaging strategies based on well-defined molecular markers and/or physiological features. Correspondingly, a large collection of apoptosis imaging probes and approaches have been documented in preclinical and clinical studies. In this review, we mainly discuss microscopic imaging assays and macroscopic imaging probes, ranging in complexity from simple attachments of reporter moieties to proteins that interact with apoptotic biomarkers, to rationally designed probes that target biochemical changes. Their clinical translation will also be our focus. PMID:25825597

Full-direct method for imaging pharmacokinetic parameters in dynamic fluorescence molecular tomography

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, Guanglei, E-mail: guangleizhang@bjtu.edu.cn; Department of Biomedical Engineering, School of Computer and Information Technology, Beijing Jiaotong University, Beijing 100044; Pu, Huangsheng

2015-02-23

Images of pharmacokinetic parameters (also known as parametric images) in dynamic fluorescence molecular tomography (FMT) can provide three-dimensional metabolic information for biological studies and drug development. However, the ill-posed nature of FMT and the high temporal variation of fluorophore concentration together make it difficult to obtain accurate parametric images in small animals in vivo. In this letter, we present a method to directly reconstruct the parametric images from the boundary measurements based on hybrid FMT/X-ray computed tomography (XCT) system. This method can not only utilize structural priors obtained from the XCT system to mitigate the ill-posedness of FMT but alsomore » make full use of the temporal correlations of boundary measurements to model the high temporal variation of fluorophore concentration. The results of numerical simulation and mouse experiment demonstrate that the proposed method leads to significant improvements in the reconstruction quality of parametric images.« less

Biomedical Applications of Functionalized Hollow Mesoporous Silica Nanoparticles: Focusing on Molecular Imaging

PubMed Central

Shi, Sixiang; Chen, Feng; Cai, Weibo

2013-01-01

Hollow mesoporous silica nanoparticles (HMSNs), with a large cavity inside each original mesoporous silica nanoparticle (MSN), have recently gained increasing interest due to their tremendous potential for cancer imaging and therapy. The last several years have witnessed a rapid development in engineering of functionalized HMSNs (i.e. f-HMSNs) with various types of inorganic functional nanocrystals integrated into the system for imaging and therapeutic applications. In this review article, we summarize the recent progress in the design and biological applications of f-HMSNs, with a special emphasis on molecular imaging. Commonly used synthetic strategies for the generation of high quality HMSNs will be discussed in detail, followed by a systematic review of engineered f-HMSNs for optical, positron emission tomography, magnetic resonance, and ultrasound imaging in preclinical studies. Lastly, we also discuss the challenges and future research directions regarding the use of f-HMSNs for cancer imaging and therapy. PMID:24279491

Molecular Imaging of Inflammation in Atherosclerosis

PubMed Central

Wildgruber, Moritz; Swirski, Filip K.; Zernecke, Alma

2013-01-01

Acute rupture of vulnerable plaques frequently leads to myocardial infarction and stroke. Within the last decades, several cellular and molecular players have been identified that promote atherosclerotic lesion formation, maturation and plaque rupture. It is now widely recognized that inflammation of the vessel wall and distinct leukocyte subsets are involved throughout all phases of atherosclerotic lesion development. The mechanisms that render a stable plaque unstable and prone to rupture, however, remain unknown and the identification of the vulnerable plaque remains a major challenge in cardiovascular medicine. Imaging technologies used in the clinic offer minimal information about the underlying biology and potential risk for rupture. New imaging technologies are therefore being developed, and in the preclinical setting have enabled new and dynamic insights into the vessel wall for a better understanding of this complex disease. Molecular imaging has the potential to track biological processes, such as the activity of cellular and molecular biomarkers in vivo and over time. Similarly, novel imaging technologies specifically detect effects of therapies that aim to stabilize vulnerable plaques and silence vascular inflammation. Here we will review the potential of established and new molecular imaging technologies in the setting of atherosclerosis, and discuss the cumbersome steps required for translating molecular imaging approaches into the clinic. PMID:24312156

Neuroradiology and histopathology in two cases of adult medulloblastoma.

PubMed

Romero-Rojas, Alfredo E; Diaz-Perez, Julio A; Raju, Sharat; Lozano-Castillo, Alfonso

2014-04-01

Medulloblastoma (MB) is the most common central nervous system neoplasm in children and only rarely presents in the adult population. Recent molecular biology findings have characterized MB as a heterogeneous neoplasm distinguished by well-defined tumour subsets each with specific histologic and molecular features. Available immunohistochemical stains can now be used to differentiate the distinct molecular types of MB. This report analyzed the histopathologic and neuroradiologic features of two new cases of adult MB. Imaging studies in these patients revealed the morphological appearance of high-grade, well-circumscribed heterogeneous tumours with necrosis, located laterally within the posterior cranial fossa. Histopathology of resected samples demonstrated high-grade tumours (WHO grade IV) containing sheets of undifferentiated neural cells with high mitotic activity and evidence of necrosis. The histopathologic and molecular characteristics of these cases of MB are reviewed for potential applications in new molecular methods of imaging.

Optical imaging probes in oncology

PubMed Central

Martelli, Cristina; Dico, Alessia Lo; Diceglie, Cecilia; Lucignani, Giovanni; Ottobrini, Luisa

2016-01-01

Cancer is a complex disease, characterized by alteration of different physiological molecular processes and cellular features. Keeping this in mind, the possibility of early identification and detection of specific tumor biomarkers by non-invasive approaches could improve early diagnosis and patient management. Different molecular imaging procedures provide powerful tools for detection and non-invasive characterization of oncological lesions. Clinical studies are mainly based on the use of computed tomography, nuclear-based imaging techniques and magnetic resonance imaging. Preclinical imaging in small animal models entails the use of dedicated instruments, and beyond the already cited imaging techniques, it includes also optical imaging studies. Optical imaging strategies are based on the use of luminescent or fluorescent reporter genes or injectable fluorescent or luminescent probes that provide the possibility to study tumor features even by means of fluorescence and luminescence imaging. Currently, most of these probes are used only in animal models, but the possibility of applying some of them also in the clinics is under evaluation. The importance of tumor imaging, the ease of use of optical imaging instruments, the commercial availability of a wide range of probes as well as the continuous description of newly developed probes, demonstrate the significance of these applications. The aim of this review is providing a complete description of the possible optical imaging procedures available for the non-invasive assessment of tumor features in oncological murine models. In particular, the characteristics of both commercially available and newly developed probes will be outlined and discussed. PMID:27145373

Cyanine-based probe\\tag-peptide pair fluorescence protein imaging and fluorescence protein imaging methods

DOEpatents

Mayer-Cumblidge, M. Uljana; Cao, Haishi

2013-01-15

A molecular probe comprises two arsenic atoms and at least one cyanine based moiety. A method of producing a molecular probe includes providing a molecule having a first formula, treating the molecule with HgOAc, and subsequently transmetallizing with AsCl.sub.3. The As is liganded to ethanedithiol to produce a probe having a second formula. A method of labeling a peptide includes providing a peptide comprising a tag sequence and contacting the peptide with a biarsenical molecular probe. A complex is formed comprising the tag sequence and the molecular probe. A method of studying a peptide includes providing a mixture containing a peptide comprising a peptide tag sequence, adding a biarsenical probe to the mixture, and monitoring the fluorescence of the mixture.

Cyanine-based probe\\tag-peptide pair for fluorescence protein imaging and fluorescence protein imaging methods

DOEpatents

Mayer-Cumblidge, M Uljana [Richland, WA; Cao, Haishi [Richland, WA

2010-08-17

A molecular probe comprises two arsenic atoms and at least one cyanine based moiety. A method of producing a molecular probe includes providing a molecule having a first formula, treating the molecule with HgOAc, and subsequently transmetallizing with AsCl.sub.3. The As is liganded to ethanedithiol to produce a probe having a second formula. A method of labeling a peptide includes providing a peptide comprising a tag sequence and contacting the peptide with a biarsenical molecular probe. A complex is formed comprising the tag sequence and the molecular probe. A method of studying a peptide includes providing a mixture containing a peptide comprising a peptide tag sequence, adding a biarsenical probe to the mixture, and monitoring the fluorescence of the mixture.

Characterization of novel molecular photoacoustic contrast agents for in vivo photoacoustic tomography

NASA Astrophysics Data System (ADS)

Laoui, Samir

Photoacoustic tomography is a hybrid imaging modality that takes advantage of the high contrast of pure optical imaging and the high intrinsic resolution of ultrasound without the necessity of ionizing radiation. Photoacoustic imaging (PM) is neither purely optical nor purely acoustical in nature, but a combination of the two. It is fundamentally based on light excitation and ultrasonic detection. Photoacoustic imaging has been successful without the introduction of exogenous contrast agents; however, to image deeper regions of biological tissue, a contrast agent is necessary. Several types of photoacoustic contrast agents have been made available for diagnostic purposes; however, the majority of literature has focused on gold nanoparticle systems for which the surface-plasmon resonance effect is important. The only option currently available for molecular PM contrast agents is to choose an existing near infrared absorbing fluorescent probes with the hope that they may generate a substantial photoacoustic (PA) response. However, these dyes have been designed with an optimized fluorescence emission response and are not anticipated to generate an adequate photoacoustic response. This dissertation addresses this lack of precedence in the literature for understanding the mechanism of a photoacoustic signal generation from strongly absorbing dye molecules including BODIPY, cyanine and curcumin systems. This work represents preliminary efforts in bringing novel molecular photoacoustic contrast agents (MPACs) into the photoacoustic imaging arena. To this end, photoacoustic and optical Z-scan experiments, and quenching studies were employed to demonstrate correlation of photoacoustic emission enhancement with excited state absorption mechanisms. To investigate further the photoacoustic emission in a practical imaging setting, MPACs were imaged using a recently developed photoacoustic imaging tomography system which was constructed exclusively for the purpose of this study.

Activateable Imaging Probes Light Up Inside Cancer Cells | Center for Cancer Research

Cancer.gov

Imaging can be used to help diagnose cancer as well as monitor tumor progression and response to treatment. The field of molecular imaging focuses on techniques capable of detecting specific molecular targets associated with cancer; the agents used for molecular imaging—often called probes—are multifunctional, with components that allow them to both interact with their

Towards a successful clinical implementation of fluorescence-guided surgery.

PubMed

Snoeks, T J A; van Driel, P B A A; Keereweer, S; Aime, S; Brindle, K M; van Dam, G M; Löwik, C W G M; Ntziachristos, V; Vahrmeijer, A L

2014-04-01

During the European Molecular Imaging Meeting (EMIM) 2013, the fluorescence-guided surgery study group held its inaugural session to discuss the clinical implementation of fluorescence-guided surgery. The general aim of this study group is to discuss and identify the steps required to successfully and safely bring intraoperative fluorescence imaging to the clinics. The focus group intends to use synergies between interested groups as a tool to address regulatory and implementation hurdles in Europe and operates within the intraoperative focus group of the World Molecular Imaging Society (WMIS) that promotes the same interests at the WMIS level. The major topics on the critical path of implementation identified within the study group were quality controls and standards for ensuring accurate imaging and the ability to compare results from different studies, regulatory affairs, and strategies to increase awareness among physicians, regulators, insurance companies, and a broader audience. These hurdles, and the possible actions discussed to overcome them, are summarized in this report. Furthermore, a number of recommendations for the future shape of the fluorescence-guided study group are discussed. A main driving conclusion remains that intraoperative imaging has great clinical potential and that many of the solutions required are best addressed with the community working together to optimally promote and accelerate the clinical implementation of fluorescence imaging towards improving surgical procedures.

Studies for the Loss of Atomic and Molecular Species from Io

NASA Technical Reports Server (NTRS)

Smyth, William H.

1999-01-01

A summary discussion of research undertaken in this project is presented and is related to six published papers attached in the appendix. The discussion is divided into six sections describing a variety of studies for the loss of atomic and molecular species from Io. They include studies for: (1) atomic sodium, (2) SO2, (3) O and S, (4) spectacular high-spatial resolution ultraviolet image observations of O, S, and possibly H in Io's atmosphere and/or corona acquired by the Space Telescope Imaging Spectrometer (STIS) of the Hubble Space Telescope (HST), (5) spectacular high-spatial resolution visible Io eclipse image observations acquired by the Solid State Imager (SSI) of Galileo spacecraft, (6) ground-based observations acquired by the Solid State Imager (SSI) of Galileo spacecraft, and (7) ground-based observations of Io's neutral cloud in [OI] 6300 angstrom emission. New source rates at Io's exobase for SO2, O, and H are given and a variety of interesting implications for Io's atmosphere and for the Io plasma torus are discussed. Appendices that are comprised of articles published during the contract are also presented.

In vivo molecular and genomic imaging: new challenges for imaging physics.

PubMed

Cherry, Simon R

2004-02-07

The emerging and rapidly growing field of molecular and genomic imaging is providing new opportunities to directly visualize the biology of living organisms. By combining our growing knowledge regarding the role of specific genes and proteins in human health and disease, with novel ways to target these entities in a manner that produces an externally detectable signal, it is becoming increasingly possible to visualize and quantify specific biological processes in a non-invasive manner. All the major imaging modalities are contributing to this new field, each with its unique mechanisms for generating contrast and trade-offs in spatial resolution, temporal resolution and sensitivity with respect to the biological process of interest. Much of the development in molecular imaging is currently being carried out in animal models of disease, but as the field matures and with the development of more individualized medicine and the molecular targeting of new therapeutics, clinical translation is inevitable and will likely forever change our approach to diagnostic imaging. This review provides an introduction to the field of molecular imaging for readers who are not experts in the biological sciences and discusses the opportunities to apply a broad range of imaging technologies to better understand the biology of human health and disease. It also provides a brief review of the imaging technology (particularly for x-ray, nuclear and optical imaging) that is being developed to support this new field.

TOPICAL REVIEW: In vivo molecular and genomic imaging: new challenges for imaging physics

NASA Astrophysics Data System (ADS)

Cherry, Simon R.

2004-02-01

The emerging and rapidly growing field of molecular and genomic imaging is providing new opportunities to directly visualize the biology of living organisms. By combining our growing knowledge regarding the role of specific genes and proteins in human health and disease, with novel ways to target these entities in a manner that produces an externally detectable signal, it is becoming increasingly possible to visualize and quantify specific biological processes in a non-invasive manner. All the major imaging modalities are contributing to this new field, each with its unique mechanisms for generating contrast and trade-offs in spatial resolution, temporal resolution and sensitivity with respect to the biological process of interest. Much of the development in molecular imaging is currently being carried out in animal models of disease, but as the field matures and with the development of more individualized medicine and the molecular targeting of new therapeutics, clinical translation is inevitable and will likely forever change our approach to diagnostic imaging. This review provides an introduction to the field of molecular imaging for readers who are not experts in the biological sciences and discusses the opportunities to apply a broad range of imaging technologies to better understand the biology of human health and disease. It also provides a brief review of the imaging technology (particularly for x-ray, nuclear and optical imaging) that is being developed to support this new field.

Reconstruction algorithms based on l1-norm and l2-norm for two imaging models of fluorescence molecular tomography: a comparative study.

PubMed

Yi, Huangjian; Chen, Duofang; Li, Wei; Zhu, Shouping; Wang, Xiaorui; Liang, Jimin; Tian, Jie

2013-05-01

Fluorescence molecular tomography (FMT) is an important imaging technique of optical imaging. The major challenge of the reconstruction method for FMT is the ill-posed and underdetermined nature of the inverse problem. In past years, various regularization methods have been employed for fluorescence target reconstruction. A comparative study between the reconstruction algorithms based on l1-norm and l2-norm for two imaging models of FMT is presented. The first imaging model is adopted by most researchers, where the fluorescent target is of small size to mimic small tissue with fluorescent substance, as demonstrated by the early detection of a tumor. The second model is the reconstruction of distribution of the fluorescent substance in organs, which is essential to drug pharmacokinetics. Apart from numerical experiments, in vivo experiments were conducted on a dual-modality FMT/micro-computed tomography imaging system. The experimental results indicated that l1-norm regularization is more suitable for reconstructing the small fluorescent target, while l2-norm regularization performs better for the reconstruction of the distribution of fluorescent substance.

Transferring biomarker into molecular probe: Melanin nanoparticle as a naturally active platform for multimodality imaging

DOE PAGES

Fan, Quli; Cheng, Kai; Hu, Xiang; ...

2014-10-07

Developing multifunctional and easily prepared nanoplatforms with integrated different modalities is highly challenging for molecular imaging. Here, we report the successful transfer of an important molecular target, melanin, into a novel multimodality imaging nanoplatform. Melanin is abundantly expressed in melanotic melanomas and thus has been actively studied as a target for melanoma imaging. In our work, the multifunctional biopolymer nanoplatform based on ultrasmall (<10 nm) water-soluble melanin nanoparticle (MNP) was developed and showed unique photoacoustic property and natural binding ability with metal ions (for example, 64Cu 2+, Fe 3+). Therefore, MNP can serve not only as a photoacoustic contrast agent,more » but also as a nanoplatform for positron emission tomography (PET) and magnetic resonance imaging (MRI). Traditional passive nanoplatforms require complicated and time-consuming processes for prebuilding reporting moieties or chemical modifications using active groups to integrate different contrast properties into one entity. In comparison, utilizing functional biomarker melanin can greatly simplify the building process. We further conjugated α vβ 3 integrins, cyclic c(RGDfC) peptide, to MNPs to allow for U87MG tumor accumulation due to its targeting property combined with the enhanced permeability and retention (EPR) effect. As a result, the multimodal properties of MNPs demonstrate the high potential of endogenous materials with multifunctions as nanoplatforms for molecular theranostics and clinical translation.« less

Early detection and longitudinal imaging of cancer micrometastases using biofunctionalized rare-earth albumin nanocomposites

NASA Astrophysics Data System (ADS)

Zevon, M.; Kantamneni, H.; Ganapathy, V.; Higgins, L.; Mingozzi, M.; Pierce, M.; Riman, R.; Roth, C. M.; Moghe, P. V.

2016-05-01

Success of personalized medicine in cancer therapy depends on the ability to identify and molecularly phenotype tumors. Current clinical imaging techniques cannot be integrated with precision molecular medicine at the level of single cells or microlesions due to limited resolution. In this work we use molecularly targeted infrared emitting optical probes to identify and characterize metastatic microlesions prior to their detection with clinically relevant imaging modalities. These contrast agents form the basis of an in vivo optical imaging system capable of resolving internal microlesions, filling a critical unmet need in cancer imaging.

State-of-the-art molecular imaging in esophageal cancer management: implications for diagnosis, prognosis, and treatment

PubMed Central

Lin, Jolinta; Kligerman, Seth; Goel, Rakhi; Sajedi, Payam; Suntharalingam, Mohan

2015-01-01

Molecular imaging techniques are increasingly being used in addition to standard imaging methods such as endoscopic ultrasound (EUS) and computed tomography (CT) for many cancers including those of the esophagus. In this review, we will discuss the utility of the most widely used molecular imaging technique, 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET). 18F-FDG PET has a variety of potential applications ranging from improving staging accuracy at the time of initial diagnosis to assisting in radiation target volume delineation. Furthermore, 18F-FDG PET can be used to evaluate treatment response after completion of neoadjuvant therapy or potentially during neoadjuvant therapy. Finally, we will also discuss other novel molecular imaging techniques that have potential to further improve cancer care. PMID:25642333

Progress in molecular imaging in endoscopy and endomicroscopy for cancer imaging

PubMed Central

Khondee, Supang; Wang, Thomas D.

2014-01-01

Imaging is an essential tool for effective cancer management. Endoscopes are important medical instruments for performing in vivo imaging in hollow organs. Early detection of cancer can be achieved with surveillance using endoscopy, and has been shown to reduce mortality and to improve outcomes. Recently, great advancements have been made in endoscopic instruments, including new developments in optical designs, light sources, optical fibers, miniature scanners, and multimodal systems, allowing for improved resolution, greater tissue penetration, and multispectral imaging. In addition, progress has been made in the development of highly-specific optical probes, allowing for improved specificity for molecular targets. Integration of these new endoscopic instruments with molecular probes provides a unique opportunity for significantly improving patient outcomes and has potential to further improve early detection, image guided therapy, targeted therapy, and personalized medicine. This work summarizes current and evolving endoscopic technologies, and provides an overview of various promising optical molecular probes. PMID:23502247

Understanding the molecular signatures in leaves and flowers by desorption electrospray ionization mass spectrometry (DESI MS) imaging.

PubMed

Hemalatha, R G; Pradeep, T

2013-08-07

The difference in size, shape, and chemical cues of leaves and flowers display the underlying genetic makeup and their interactions with the environment. The need to understand the molecular signatures of these fragile plant surfaces is illustrated with a model plant, Madagascar periwinkle (Catharanthus roseus (L.) G. Don). Flat, thin layer chromatographic imprints of leaves/petals were imaged using desorption electrospray ionization mass spectrometry (DESI MS), and the results were compared with electrospray ionization mass spectrometry (ESI MS) of their extracts. Tandem mass spectrometry with DESI and ESI, in conjunction with database records, confirmed the molecular species. This protocol has been extended to other plants. Implications of this study in identifying varietal differences, toxic metabolite production, changes in metabolites during growth, pest/pathogen attack, and natural stresses are shown with illustrations. The possibility to image subtle features like eye color of petals, leaf vacuole, leaf margin, and veins is demonstrated.

Molecular Images in Organic Chemistry: Assessment of Understanding in Aromaticity, Symmetry, Spectroscopy, and Shielding

ERIC Educational Resources Information Center

Ealy, Julie B.; Hermanson, Jim

2006-01-01

When students take General Chemistry there are substantially fewer molecular images than they will encounter in Organic Chemistry. The molecular images Organic Chemistry students see in their textbooks are ones that use dashes and wedges to represent 2D and semi 3D views, ball and spoke, ball and wire, and structural formulas, to name just a few.…

Mapping reversible photoswitching of molecular-resistance fluctuations during the conformational transformation of azobenzene-terminated molecular switches.

PubMed

Cho, Duckhyung; Yang, Myungjae; Shin, Narae; Hong, Seunghun

2018-06-07

We report a direct mapping and analysis of electrical noise in azobenzene-terminated molecular monolayers, revealing reversible photoswitching of the molecular-resistance fluctuations in the layers. In this work, a conducting atomic force microscope combined with a homemade spectrum analyzer was used to image electrical current and noise at patterned self-assembled monolayers (SAMs) of azobenzene-terminated molecular wires on a gold substrate. We analyzed the current and noise imaging data to obtain maps of molecular resistances and amount of mean-square fluctuations in the resistances of the regions of trans-azobenzene and a cis/trans-azobenzene mixture. We revealed that the fluctuations in the molecular resistances in the SAMs were enhanced after the trans-to-cis isomerization, while the resistances were reduced. This result could be attributed to enhanced disorders in the molecular arrangements in the cis-SAMs. Furthermore, we observed that the changes in the resistance fluctuations were reversible with respect to repeated trans-to-cis and cis-to-trans isomerizations, indicating that the effects originated from reversible photoswitching of the molecular structures rather than irreversible damages of the molecules. These findings provide valuable insights into the electrical fluctuations in photoswitchable molecules, which could be utilized in further studies on molecular switches and molecular electronics in general. © 2018 IOP Publishing Ltd.

Latest advances in molecular imaging instrumentation.

PubMed

Pichler, Bernd J; Wehrl, Hans F; Judenhofer, Martin S

2008-06-01

This review concentrates on the latest advances in molecular imaging technology, including PET, MRI, and optical imaging. In PET, significant improvements in tumor detection and image resolution have been achieved by introducing new scintillation materials, iterative image reconstruction, and correction methods. These advances enabled the first clinical scanners capable of time-of-flight detection and incorporating point-spread-function reconstruction to compensate for depth-of-interaction effects. In the field of MRI, the most important developments in recent years have mainly been MRI systems with higher field strengths and improved radiofrequency coil technology. Hyperpolarized imaging, functional MRI, and MR spectroscopy provide molecular information in vivo. A special focus of this review article is multimodality imaging and, in particular, the emerging field of combined PET/MRI.

Emerging Themes in Image Informatics and Molecular Analysis for Digital Pathology.

PubMed

Bhargava, Rohit; Madabhushi, Anant

2016-07-11

Pathology is essential for research in disease and development, as well as for clinical decision making. For more than 100 years, pathology practice has involved analyzing images of stained, thin tissue sections by a trained human using an optical microscope. Technological advances are now driving major changes in this paradigm toward digital pathology (DP). The digital transformation of pathology goes beyond recording, archiving, and retrieving images, providing new computational tools to inform better decision making for precision medicine. First, we discuss some emerging innovations in both computational image analytics and imaging instrumentation in DP. Second, we discuss molecular contrast in pathology. Molecular DP has traditionally been an extension of pathology with molecularly specific dyes. Label-free, spectroscopic images are rapidly emerging as another important information source, and we describe the benefits and potential of this evolution. Third, we describe multimodal DP, which is enabled by computational algorithms and combines the best characteristics of structural and molecular pathology. Finally, we provide examples of application areas in telepathology, education, and precision medicine. We conclude by discussing challenges and emerging opportunities in this area.

Emerging Themes in Image Informatics and Molecular Analysis for Digital Pathology

PubMed Central

Bhargava, Rohit; Madabhushi, Anant

2017-01-01

Pathology is essential for research in disease and development, as well as for clinical decision making. For more than 100 years, pathology practice has involved analyzing images of stained, thin tissue sections by a trained human using an optical microscope. Technological advances are now driving major changes in this paradigm toward digital pathology (DP). The digital transformation of pathology goes beyond recording, archiving, and retrieving images, providing new computational tools to inform better decision making for precision medicine. First, we discuss some emerging innovations in both computational image analytics and imaging instrumentation in DP. Second, we discuss molecular contrast in pathology. Molecular DP has traditionally been an extension of pathology with molecularly specific dyes. Label-free, spectroscopic images are rapidly emerging as another important information source, and we describe the benefits and potential of this evolution. Third, we describe multimodal DP, which is enabled by computational algorithms and combines the best characteristics of structural and molecular pathology. Finally, we provide examples of application areas in telepathology, education, and precision medicine. We conclude by discussing challenges and emerging opportunities in this area. PMID:27420575

Smart Contrast Agents for Magnetic Resonance Imaging.

PubMed

Bonnet, Célia S; Tóth, Éva

2016-01-01

By visualizing bioactive molecules or biological parameters in vivo, molecular imaging is searching for information at the molecular level in living organisms. In addition to contributing to earlier and more personalized diagnosis in medicine, it also helps understand and rationalize the molecular factors underlying physiological and pathological processes. In magnetic resonance imaging (MRI), complexes of paramagnetic metal ions, mostly lanthanides, are commonly used to enhance the intrinsic image contrast. They rely either on the relaxation effect of these metal chelates (T(1) agents), or on the phenomenon of paramagnetic chemical exchange saturation transfer (PARACEST agents). In both cases, responsive molecular magnetic resonance imaging probes can be designed to report on various biomarkers of biological interest. In this context, we review recent work in the literature and from our group on responsive T(1) and PARACEST MRI agents for the detection of biogenic metal ions (such as calcium or zinc), enzymatic activities, or neurotransmitter release. These examples illustrate the general strategies that can be applied to create molecular imaging agents with an MRI detectable response to biologically relevant parameters.

Ultrasound Biomicroscopy in Small Animal Research: Applications in Molecular and Preclinical Imaging

PubMed Central

Greco, A.; Mancini, M.; Gargiulo, S.; Gramanzini, M.; Claudio, P. P.; Brunetti, A.; Salvatore, M.

2012-01-01

Ultrasound biomicroscopy (UBM) is a noninvasive multimodality technique that allows high-resolution imaging in mice. It is affordable, widely available, and portable. When it is coupled to Doppler ultrasound with color and power Doppler, it can be used to quantify blood flow and to image microcirculation as well as the response of tumor blood supply to cancer therapy. Target contrast ultrasound combines ultrasound with novel molecular targeted contrast agent to assess biological processes at molecular level. UBM is useful to investigate the growth and differentiation of tumors as well as to detect early molecular expression of cancer-related biomarkers in vivo and to monitor the effects of cancer therapies. It can be also used to visualize the embryological development of mice in uterus or to examine their cardiovascular development. The availability of real-time imaging of mice anatomy allows performing aspiration procedures under ultrasound guidance as well as the microinjection of cells, viruses, or other agents into precise locations. This paper will describe some basic principles of high-resolution imaging equipment, and the most important applications in molecular and preclinical imaging in small animal research. PMID:22163379

Imaging mass spectrometry data reduction: automated feature identification and extraction.

PubMed

McDonnell, Liam A; van Remoortere, Alexandra; de Velde, Nico; van Zeijl, René J M; Deelder, André M

2010-12-01

Imaging MS now enables the parallel analysis of hundreds of biomolecules, spanning multiple molecular classes, which allows tissues to be described by their molecular content and distribution. When combined with advanced data analysis routines, tissues can be analyzed and classified based solely on their molecular content. Such molecular histology techniques have been used to distinguish regions with differential molecular signatures that could not be distinguished using established histologic tools. However, its potential to provide an independent, complementary analysis of clinical tissues has been limited by the very large file sizes and large number of discrete variables associated with imaging MS experiments. Here we demonstrate data reduction tools, based on automated feature identification and extraction, for peptide, protein, and lipid imaging MS, using multiple imaging MS technologies, that reduce data loads and the number of variables by >100×, and that highlight highly-localized features that can be missed using standard data analysis strategies. It is then demonstrated how these capabilities enable multivariate analysis on large imaging MS datasets spanning multiple tissues. Copyright © 2010 American Society for Mass Spectrometry. Published by Elsevier Inc. All rights reserved.

Molecular Imaging of Tumors Using a Quantitative T1 Mapping Technique via Magnetic Resonance Imaging

PubMed Central

Herrmann, Kelsey; Johansen, Mette L.; Craig, Sonya E.; Vincent, Jason; Howell, Michael; Gao, Ying; Lu, Lan; Erokwu, Bernadette; Agnes, Richard S.; Lu, Zheng-Rong; Pokorski, Jonathan K.; Basilion, James; Gulani, Vikas; Griswold, Mark; Flask, Chris; Brady-Kalnay, Susann M.

2015-01-01

Magnetic resonance imaging (MRI) of glioblastoma multiforme (GBM) with molecular imaging agents would allow for the specific localization of brain tumors. Prior studies using T1-weighted MR imaging demonstrated that the SBK2-Tris-(Gd-DOTA)3 molecular imaging agent labeled heterotopic xenograft models of brain tumors more intensely than non-specific contrast agents using conventional T1-weighted imaging techniques. In this study, we used a dynamic quantitative T1 mapping strategy to more objectively compare intra-tumoral retention of the SBK2-Tris-(Gd-DOTA)3 agent over time in comparison to non-targeted control agents. Our results demonstrate that the targeted SBK2-Tris-(Gd-DOTA)3 agent, a scrambled-Tris-(Gd-DOTA)3 control agent, and the non-specific clinical contrast agent Optimark™ all enhanced flank tumors of human glioma cells with similar maximal changes on T1 mapping. However, the retention of the agents differs. The non-specific agents show significant recovery within 20 min by an increase in T1 while the specific agent SBK2-Tris-(Gd-DOTA)3 is retained in the tumors and shows little recovery over 60 min. The retention effect is demonstrated by percent change in T1 values and slope calculations as well as by calculations of gadolinium concentration in tumor compared to muscle. Quantitative T1 mapping demonstrates the superior binding and retention in tumors of the SBK2-Tris-(Gd-DOTA)3 agent over time compared to the non-specific contrast agent currently in clinical use. PMID:26435847

Nanoparticles in practice for molecular-imaging applications: An overview.

PubMed

Padmanabhan, Parasuraman; Kumar, Ajay; Kumar, Sundramurthy; Chaudhary, Ravi Kumar; Gulyás, Balázs

2016-09-01

Nanoparticles (NPs) are playing a progressively more significant role in multimodal and multifunctional molecular imaging. The agents like Superparamagnetic iron oxide (SPIO), manganese oxide (MnO), gold NPs/nanorods and quantum dots (QDs) possess specific properties like paramagnetism, superparamagnetism, surface plasmon resonance (SPR) and photoluminescence respectively. These specific properties make them able for single/multi-modal and single/multi-functional molecular imaging. NPs generally have nanomolar or micromolar sensitivity range and can be detected via imaging instrumentation. The distinctive characteristics of these NPs make them suitable for imaging, therapy and delivery of drugs. Multifunctional nanoparticles (MNPs) can be produced through either modification of shell or surface or by attaching an affinity ligand to the nanoparticles. They are utilized for targeted imaging by magnetic resonance imaging (MRI), single photon emission computed tomography (SPECT), positron emission tomography (PET), computed tomography (CT), photo acoustic imaging (PAI), two photon or fluorescent imaging and ultra sound etc. Toxicity factor of NPs is also a very important concern and toxic effect should be eliminated. First generation NPs have been designed, developed and tested in living subjects and few of them are already in clinical use. In near future, molecular imaging will get advanced with multimodality and multifunctionality to detect diseases like cancer, neurodegenerative diseases, cardiac diseases, inflammation, stroke, atherosclerosis and many others in their early stages. In the current review, we discussed single/multifunctional nanoparticles along with molecular imaging modalities. The present article intends to reveal recent avenues for nanomaterials in multimodal and multifunctional molecular imaging through a review of pertinent literatures. The topic emphasises on the distinctive characteristics of nanomaterial which makes them, suitable for biomedical imaging, therapy and delivery of drugs. This review is more informative of indicative technologies which will be helpful in a way to plan, understand and lead the nanotechnology related work. Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Genetic engineered molecular imaging probes for applications in cell therapy: emphasis on MRI approach

PubMed Central

Cho, In K; Wang, Silun; Mao, Hui; Chan, Anthony WS

2016-01-01

Recent advances in stem cell-based regenerative medicine, cell replacement therapy, and genome editing technologies (i.e. CRISPR-Cas 9) have sparked great interest in in vivo cell monitoring. Molecular imaging promises a unique approach to noninvasively monitor cellular and molecular phenomena, including cell survival, migration, proliferation, and even differentiation at the whole organismal level. Several imaging modalities and strategies have been explored for monitoring cell grafts in vivo. We begin this review with an introduction describing the progress in stem cell technology, with a perspective toward cell replacement therapy. The importance of molecular imaging in reporting and assessing the status of cell grafts and their relation to the local microenvironment is highlighted since the current knowledge gap is one of the major obstacles in clinical translation of stem cell therapy. Based on currently available imaging techniques, we provide a brief discussion on the pros and cons of each imaging modality used for monitoring cell grafts with particular emphasis on magnetic resonance imaging (MRI) and the reporter gene approach. Finally, we conclude with a comprehensive discussion of future directions of applying molecular imaging in regenerative medicine to emphasize further the importance of correlating cell graft conditions and clinical outcomes to advance regenerative medicine. PMID:27766183

Molecular imaging of prostate cancer: translating molecular biology approaches into the clinical realm.

PubMed

Vargas, Hebert Alberto; Grimm, Jan; F Donati, Olivio; Sala, Evis; Hricak, Hedvig

2015-05-01

The epidemiology of prostate cancer has dramatically changed since the introduction of prostate-specific antigen (PSA) screening in the 1980's. Most prostate cancers today are detected at early stages of the disease and are considered 'indolent'; however, some patients' prostate cancers demonstrate a more aggressive behaviour which leads to rapid progression and death. Increasing understanding of the biology underlying the heterogeneity that characterises this disease has led to a continuously evolving role of imaging in the management of prostate cancer. Functional and metabolic imaging techniques are gaining importance as the impact on the therapeutic paradigm has shifted from structural tumour detection alone to distinguishing patients with indolent tumours that can be managed conservatively (e.g., by active surveillance) from patients with more aggressive tumours that may require definitive treatment with surgery or radiation. In this review, we discuss advanced imaging techniques that allow direct visualisation of molecular interactions relevant to prostate cancer and their potential for translation to the clinical setting in the near future. The potential use of imaging to follow molecular events during drug therapy as well as the use of imaging agents for therapeutic purposes will also be discussed. • Advanced imaging techniques allow direct visualisation of molecular interactions in prostate cancer. • MRI/PET, optical and Cerenkov imaging facilitate the translation of molecular biology. • Multiple compounds targeting PSMA expression are currently undergoing clinical translation. • Other targets (e.g., PSA, prostate-stem cell antigen, GRPR) are in development.

Molecular orbital imaging via above-threshold ionization with circularly polarized pulses.

PubMed

Zhu, Xiaosong; Zhang, Qingbin; Hong, Weiyi; Lu, Peixiang; Xu, Zhizhan

2011-07-18

Above-threshold ionization (ATI) for aligned or orientated linear molecules by circularly polarized laser pulsed is investigated. It is found that the all-round structural information of the molecular orbital is extracted with only one shot by the circularly polarized probe pulse rather than with multi-shot detections in a linearly polarized case. The obtained photoelectron momentum spectrum directly depicts the symmetry and electron distribution of the occupied molecular orbital, which results from the strong sensitivity of the ionization probability to these structural features. Our investigation indicates that the circularly polarized probe scheme would present a simple method to study the angle-dependent ionization and image the occupied electronic orbital.

The feasibility study on 3-dimensional fluorescent x-ray computed tomography using the pinhole effect for biomedical applications.

PubMed

Sunaguchi, Naoki; Yuasa, Tetsuya; Hyodo, Kazuyuki; Zeniya, Tsutomu

2013-01-01

We propose a 3-dimensional fluorescent x-ray computed tomography (CT) pinhole collimator, aimed at providing molecular imaging with quantifiable measures and sub-millimeter spatial resolution. In this study, we demonstrate the feasibility of this concept and investigate imaging properties such as spatial resolution, contrast resolution and quantifiable measures, by imaging physical phantoms using a preliminary imaging system developed with monochromatic synchrotron x rays constructed at the BLNE-7A experimental line at KEK, Japan.

Targeting Phosphatidylserine with a 64Cu-Labeled Peptide for Molecular Imaging of Apoptosis.

PubMed

Perreault, Amanda; Richter, Susan; Bergman, Cody; Wuest, Melinda; Wuest, Frank

2016-10-03

Molecular imaging of programmed cell death (apoptosis) in vivo is an innovative strategy for early assessment of treatment response and treatment efficacy in cancer patients. Externalization of phosphatidylserine (PS) to the cell membrane surface of dying cells makes this phospholipid an attractive molecular target for the development of apoptosis imaging probes. In this study, we have radiolabeled PS-binding 14-mer peptide FNFRLKAGAKIRFG (PSBP-6) with positron-emitter copper-64 ( 64 Cu) for PET imaging of apoptosis. Peptide PSBP-6 was conjugated with radiometal chelator 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA) through an aminovaleric acid (Ava) linker for subsequent radiolabeling with 64 Cu to prepare radiotracer 64 Cu-NOTA-Ava-PSBP-6. PS-binding potencies of PSBP-6, NOTA-Ava-PSBP-6, and nat Cu-NOTA-Ava-PSBP-6 were determined in a competitive radiometric PS-binding assay. Radiotracer 64 Cu-NOTA-Ava-PSBP-6 was studied in camptothecin-induced apoptotic EL4 mouse lymphoma cells and in a murine EL4 tumor model of apoptosis using dynamic PET imaging. Peptide PSBP-6 was also conjugated via an Ava linker with fluorescein isothiocyanate (FITC). FITC-Ava-PSBP-6 was evaluated in flow cytometry and fluorescence confocal microscopy experiments. Radiopeptide 64 Cu-NOTA-Ava-PSBP-6 was synthesized in high radiochemical yields of >95%. The IC 50 values for PS-binding potency of PSBP-6, NOTA-Ava-PSBP-6, and nat Cu-NOTA-PSBP-6 were 600 μM, 30 μM, and 23 μM, respectively. A competitive radiometric cell binding assay confirmed binding of 64 Cu-NOTA-Ava-PSBP-6 to camptothecin-induced apoptotic EL4 cells in a Ca 2+ -independent manner. PET imaging studies demonstrated significantly higher uptake of 64 Cu-NOTA-Ava-PSBP-6 in apoptotic EL4 tumors (SUV 5min 0.95 ± 0.04) compared to control tumors (SUV 5min 0.74 ± 0.03). Flow cytometry studies showed significantly higher binding of FITC-Ava-PSBP-6 to EL4 cells treated with camptothecin compared to untreated cells. Fluorescence microscopy studies revealed that FITC-Ava-PSBP-6 was binding to cell membranes of early apoptotic cells, but was internalized in late apoptotic and necrotic cells. The present study showed that radiotracer 64 Cu-NOTA-Ava-PSBP-6 holds promise as a first peptide-based PET imaging agent for molecular imaging of apoptosis. However, additional "fine-tuning" of 64 Cu-NOTA-Ava-PSBP-6 is required to enhance PS-binding potency and in vivo stability to improve tumor uptake and retention.

Optical Molecular Imaging for Diagnosing Intestinal Diseases

PubMed Central

Kim, Sang-Yeob

2013-01-01

Real-time visualization of the molecular signature of cells can be achieved with advanced targeted imaging techniques using molecular probes and fluorescence endoscopy. This molecular optical imaging in gastrointestinal endoscopy is promising for improving the detection of neoplastic lesions, their characterization for patient stratification, and the assessment of their response to molecular targeted therapy and radiotherapy. In inflammatory bowel disease, this method can be used to detect dysplasia in the presence of background inflammation and to visualize inflammatory molecular targets for assessing disease severity and prognosis. Several preclinical and clinical trials have applied this method in endoscopy; however, this field has just started to evolve. Hence, many problems have yet to be solved to enable the clinical application of this novel method. PMID:24340254

Combining Optical Coherence Tomography with Fluorescence Molecular Imaging: Towards Simultaneous Morphology and Molecular Imaging

PubMed Central

Yuan, Shuai; Roney, Celeste A.; Wierwille, Jerry; Chen, Chao-Wei; Xu, Biying; Jiang, James; Ma, Hongzhou; Cable, Alex; Summers, Ronald M.; Chen, Yu

2010-01-01

Optical coherence tomography (OCT) provides high-resolution, cross-sectional imaging of tissue microstructure in situ and in real-time, while fluorescence molecular imaging (FMI) enables the visualization of basic molecular processes. There are great interests in combining these two modalities so that the tissue's structural and molecular information can be obtained simultaneously. This could greatly benefit biomedical applications such as detecting early diseases and monitoring therapeutic interventions. In this research, an optical system that combines OCT and FMI was developed. The system demonstrated that it could co-register en face OCT and FMI images with a 2.4 × 2.4 mm field of view. The transverse resolutions of OCT and FMI of the system are both ~10 μm. Capillary tubes filled with fluorescent dye Cy 5.5 in different concentrations under a scattering medium are used as the phantom. En face OCT images of the phantoms were obtained and successfully co-registered with FMI images that were acquired simultaneously. A linear relationship between FMI intensity and dye concentration was observed. The relationship between FMI intensity and target fluorescence tube depth measured by OCT images was also observed and compared with theoretical modeling. This relationship could help in correcting reconstructed dye concentration. Imaging of colon polyps of APCmin mouse model is presented as an example of biological applications of this co-registered OCT/FMI system. PMID:20009192

Tumor Endothelial Marker Imaging in Melanomas Using Dual-Tracer Fluorescence Molecular Imaging

PubMed Central

Tichauer, Kenneth M.; Deharvengt, Sophie J.; Samkoe, Kimberley S.; Gunn, Jason R.; Bosenberg, Marcus W.; Turk, Mary-Jo; Hasan, Tayyaba; Stan, Radu V.; Pogue, Brian W.

2014-01-01

Purpose Cancer-specific endothelial markers available for intravascular binding are promising targets for new molecular therapies. In this study, a molecular imaging approach of quantifying endothelial marker concentrations (EMCI) is developed and tested in highly light-absorbing melanomas. The approach involves injection of targeted imaging tracer in conjunction with an untargeted tracer, which is used to account for nonspecific uptake and tissue optical property effects on measured targeted tracer concentrations. Procedures Theoretical simulations and a mouse melanoma model experiment were used to test out the EMCI approach. The tracers used in the melanoma experiments were fluorescently labeled anti-Plvap/PV1 antibody (plasmalemma vesicle associated protein Plvap/PV1 is a transmembrane protein marker exposed on the luminal surface of endothelial cells in tumor vasculature) and a fluorescent isotype control antibody, the uptakes of which were measured on a planar fluorescence imaging system. Results The EMCI model was found to be robust to experimental noise under reversible and irreversible binding conditions and was capable of predicting expected overexpression of PV1 in melanomas compared to healthy skin despite a 5-time higher measured fluorescence in healthy skin compared to melanoma: attributable to substantial light attenuation from melanin in the tumors. Conclusions This study demonstrates the potential of EMCI to quantify endothelial marker concentrations in vivo, an accomplishment that is currently unavailable through any other methods, either in vivo or ex vivo. PMID:24217944

Development of new PTK7-targeting aptamer-fluorescent and -radiolabelled probes for evaluation as molecular imaging agents: Lymphoma and melanoma in vivo proof of concept.

PubMed

Calzada, Victoria; Moreno, María; Newton, Jessica; González, Joel; Fernández, Marcelo; Gambini, Juan Pablo; Ibarra, Manuel; Chabalgoity, Alejandro; Deutscher, Susan; Quinn, Thomas; Cabral, Pablo; Cerecetto, Hugo

2017-02-01

Aptamers are single-stranded oligonucleotides that recognize molecular targets with high affinity and specificity. Aptamer that selectively bind to the protein tyrosine kinase-7 (PTK7) receptor, overexpressed on many cancers, has been labelled as probes for molecular imaging of cancer. Two new PTK7-targeting aptamer probes were developed by coupling frameworks from the fluorescent dye AlexaFluor647 or the 6-hydrazinonicotinamide (HYNIC) chelator-labelled to 99m Tc. The derivatizations via a 5'-aminohexyl terminal linker were done at room temperature and under mild buffer conditions. Physicochemical and biological controls for both imaging agents were performed verifying the integrity of the aptamer-conjugates by HPLC. Recognition of melanoma (B16F1) and lymphoma (A20) mouse cell lines by the aptamer was studied using cell binding, flow cytometry and confocal microscopy. Finally, in vivo imaging studies in tumour-bearing mice were performed. The new probes were able to bind to melanoma and lymphoma cell lines in vitro, the in vivo imaging in tumour-bearing mice showed different uptake behaviours showing for the fluorescent conjugate good uptake by B cell lymphoma while the radiolabelled conjugate did not display tumour uptake due to its high extravascular distribution, and both showed rapid clearance properties in tumour-bearing mice. Copyright © 2016 Elsevier Ltd. All rights reserved.

Application and Miniaturization of Linear and Nonlinear Raman Microscopy for Biomedical Imaging

NASA Astrophysics Data System (ADS)

Mittal, Richa

Current diagnostics for several disorders rely on surgical biopsy or evaluation of ex vivo bodily fluids, which have numerous drawbacks. We evaluated the potential for vibrational techniques (both linear and nonlinear Raman) as a reliable and noninvasive diagnostic tool. Raman spectroscopy is an optical technique for molecular analysis that has been used extensively in various biomedical applications. Based on demonstrated capabilities of Raman spectroscopy we evaluated the potential of the technique for providing a noninvasive diagnosis of mucopolysaccharidosis (MPS). These studies show that Raman spectroscopy can detect subtle changes in tissue biochemistry. In applications where sub-micrometer visualization of tissue compositional change is required, a transition from spectroscopy to high quality imaging is necessary. Nonlinear vibrational microscopy is sensitive to the same molecular vibrations as linear Raman, but features fast imaging capabilities. Coherent Raman scattering when combined with other nonlinear optical (NLO) techniques (like two-photon excited fluorescence and second harmonic generation) forms a collection of advanced optical techniques that provide noninvasive chemical contrast at submicron resolution. This capability to examine tissues without external molecular agents is driving the NLO approach towards clinical applications. However, the unique imaging capabilities of NLO microscopy are accompanied by complex instrument requirements. Clinical examination requires portable imaging systems for rapid inspection of tissues. Optical components utilized in NLO microscopy would then need substantial miniaturization and optimization to enable in vivo use. The challenges in designing compact microscope objective lenses and laser beam scanning mechanisms are discussed. The development of multimodal NLO probes for imaging oral cavity tissue is presented. Our prototype has been examined for ex vivo tissue imaging based on intrinsic fluorescence and SHG contrast. These studies show a potential for multiphoton compact probes to be used for real time imaging in the clinic.

Detection of hydroxyapatite in calcified cardiovascular tissues.

PubMed

Lee, Jae Sam; Morrisett, Joel D; Tung, Ching-Hsuan

2012-10-01

The objective of this study is to develop a method for selective detection of the calcific (hydroxyapatite) component in human aortic smooth muscle cells in vitro and in calcified cardiovascular tissues ex vivo. This method uses a novel optical molecular imaging contrast dye, Cy-HABP-19, to target calcified cells and tissues. A peptide that mimics the binding affinity of osteocalcin was used to label hydroxyapatite in vitro and ex vivo. Morphological changes in vascular smooth muscle cells were evaluated at an early stage of the mineralization process induced by extrinsic stimuli, osteogenic factors and a magnetic suspension cell culture. Hydroxyapatite components were detected in monolayers of these cells in the presence of osteogenic factors and a magnetic suspension environment. Atherosclerotic plaque contains multiple components including lipidic, fibrotic, thrombotic, and calcific materials. Using optical imaging and the Cy-HABP-19 molecular imaging probe, we demonstrated that hydroxyapatite components could be selectively distinguished from various calcium salts in human aortic smooth muscle cells in vitro and in calcified cardiovascular tissues, carotid endarterectomy samples and aortic valves, ex vivo. Hydroxyapatite deposits in cardiovascular tissues were selectively detected in the early stage of the calcification process using our Cy-HABP-19 probe. This new probe makes it possible to study the earliest events associated with vascular hydroxyapatite deposition at the cellular and molecular levels. This target-selective molecular imaging probe approach holds high potential for revealing early pathophysiological changes, leading to progression, regression, or stabilization of cardiovascular diseases. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Detection of Hydroxyapatite in Calcified Cardiovascular Tissues

PubMed Central

Lee, Jae Sam; Morrisett, Joel D.; Tung, Ching-Hsuan

2012-01-01

Objective The objective of this study is to develop a method for selective detection of the calcific (hydroxyapatite) component in human aortic smooth muscle cells in vitro and in calcified cardiovascular tissues ex vivo. This method uses a novel optical molecular imaging contrast dye, Cy-HABP-19, to target calcified cells and tissues. Methods A peptide that mimics the binding affinity of osteocalcin was used to label hydroxyapatite in vitro and ex vivo. Morphological changes in vascular smooth muscle cells were evaluated at an early stage of the mineralization process induced by extrinsic stimuli, osteogenic factors and a magnetic suspension cell culture. Hydroxyapatite components were detected in monolayers of these cells in the presence of osteogenic factors and a magnetic suspension environment. Results Atherosclerotic plaque contains multiple components including lipidic, fibrotic, thrombotic, and calcific materials. Using optical imaging and the Cy-HABP-19 molecular imaging probe, we demonstrated that hydroxyapatite components could be selectively distinguished from various calcium salts in human aortic smooth muscle cells in vitro and in calcified cardiovascular tissues, carotid endarterectomy samples and aortic valves, ex vivo. Conclusion Hydroxyapatite deposits in cardiovascular tissues were selectively detected in the early stage of the calcification process using our Cy-HABP-19 probe. This new probe makes it possible to study the earliest events associated with vascular hydroxyapatite deposition at the cellular and molecular levels. This target-selective molecular imaging probe approach holds high potential for revealing early pathophysiological changes, leading to progression, regression, or stabilization of cardiovascular diseases. PMID:22877867

Evaluation of 18F-labeled targeted perfluorocarbon-filled albumin microbubbles as a probe for microUS and microPET in tumor-bearing mice.

PubMed

Liao, Ai-Ho; Wu, Shih-Yen; Wang, Hsin-Ell; Weng, Chien-Hsiu; Wu, Ming-Fang; Li, Pai-Chi

2013-02-01

In this study, albumin-shelled, targeted MBs (tMBs) were first demonstrated with the expectation of visualization of biodistribution of albumin-shelled tMBs. The actual biodistribution of albumin-shelled tMBs is of vital importance either for molecular imaging or for drug delivery. Recently, albumin microbubbles (MBs) have been studied for drug and gene delivery in vitro and in vivo through cavitation. Targeted lipid-shelled MBs have been applied for ultrasound molecular imaging and conjugated with radiolabeled antibodies for whole-body biodistribution evaluations. The novelty of the work is that, in addition to the lipid tMBs, the albumin tMBs was also applied in biodistribution detection. Multimodality albumin-shelled, (18)F-SFB-labeled VEGFR2 tMBs were synthesized, and their characteristics in mice bearing MDA-MB-231 human breast cancer were investigated with micro-positron-emission tomography (microPET) and high-frequency ultrasound (microUS). Albumin-shelled MBs can be labeled with (18)F-SFB directly and conjugated with antibodies for dual molecular imaging. The albumin-shelled tMBs show a lifetime in 30min in the blood pool and a highly specific adherence to tumor vessels in mice bearing human breast cancer. From the evaluations of whole-body biodistribution, the potential of the dual molecular imaging probe for drug or gene delivery in animal experiments with albumin shelled MBs has been investigated. Copyright © 2012 Elsevier B.V. All rights reserved.

Document authentication at molecular levels using desorption atmospheric pressure chemical ionization mass spectrometry imaging.

PubMed

Li, Ming; Jia, Bin; Ding, Liying; Hong, Feng; Ouyang, Yongzhong; Chen, Rui; Zhou, Shumin; Chen, Huanwen; Fang, Xiang

2013-09-01

Molecular images of documents were obtained by sequentially scanning the surface of the document using desorption atmospheric pressure chemical ionization mass spectrometry (DAPCI-MS), which was operated in either a gasless, solvent-free or methanol vapor-assisted mode. The decay process of the ink used for handwriting was monitored by following the signal intensities recorded by DAPCI-MS. Handwritings made using four types of inks on four kinds of paper surfaces were tested. By studying the dynamic decay of the inks, DAPCI-MS imaging differentiated a 10-min old from two 4 h old samples. Non-destructive forensic analysis of forged signatures either handwritten or computer-assisted was achieved according to the difference of the contour in DAPCI images, which was attributed to the strength personalized by different writers. Distinction of the order of writing/stamping on documents and detection of illegal printings were accomplished with a spatial resolution of about 140 µm. A Matlab® written program was developed to facilitate the visualization of the similarity between signature images obtained by DAPCI-MS. The experimental results show that DAPCI-MS imaging provides rich information at the molecular level and thus can be used for the reliable document analysis in forensic applications. © 2013 The Authors. Journal of Mass Spectrometry published by John Wiley & Sons, Ltd.

A targeted nanoglobular contrast agent from host-guest self-assembly for MR cancer molecular imaging

PubMed Central

Zhou, Zhuxian; Han, Zhen; Lu, Zheng-Rong

2016-01-01

The clinical application of nanoparticular Gd(III) based contrast agents for tumor molecular MRI has been hindered by safety concerns associated with prolonged tissue retention, although they can produce strong tumor enhancement. In this study, a targeted well-defined cyclodextrin-based nanoglobular contrast agent was developed through self-assembly driven by host-guest interactions for safe and effective cancer molecular MRI. Multiple β-cyclodextrins attached POSS (polyhedral oligomeric silsesquioxane) nanoglobule was used as host molecule. Adamantane–modified macrocyclic Gd(III) contrast agent, cRGD (cyclic RGDfK peptide) targeting ligand and fluorescent probe was used as guest molecules. The targeted host-guest nanoglobular contrast agent cRGD-POSS-βCD-(DOTA-Gd) specifically bond to αvβ3 integrin in malignant 4T1 breast tumor and provided greater contrast enhancement than the corresponding non-targeted agent. The agent also provided significant fluorescence signal in tumor tissue. The histological analysis of the tumor tissue confirmed its specific and effective targeting to αvβ3 integrin. The targeted imaging agent has a potential for specific cancer molecular MR and fluorescent imaging. PMID:26874280

Molecular Imaging of Breast Cancer: Present and future directions

NASA Astrophysics Data System (ADS)

Alcantara, David; Pernia Leal, Manuel; Garcia, Irene; Garcia-Martin, Maria Luisa

2014-12-01

Medical imaging technologies have undergone explosive growth over the past few decades and now play a central role in clinical oncology. But the truly transformative power of imaging in the clinical management of cancer patients lies ahead. Today, imaging is at a crossroads, with molecularly targeted imaging agents expected to broadly expand the capabilities of conventional anatomical imaging methods. Molecular imaging will allow clinicians to not only see where a tumour is located in the body, but also to visualize the expression and activity of specific molecules (e.g. proteases and protein kinases) and biological processes (e.g. apoptosis, angiogenesis, and metastasis) that influence tumour behavior and/or response to therapy. Breast cancer, the most common cancer among women and a research area where our group is actively involved, is a very heterogeneous disease with diverse patterns of development and response to treatment. Hence, molecular imaging is expected to have a major impact on this type of cancer, leading to important improvements in diagnosis, individualized treatment, and drug development, as well as our understanding of how breast cancer arises.

Lymph Node Metastases Optical Molecular Diagnostic and Radiation Therapy

DTIC Science & Technology

2017-03-01

structures and not molecular functions. The one tool commonly used for metastases imaging is nuclear medicine. Positron emission tomography, PET, is...be visualized at a relevant stage., largely because most imaging is based upon structures and not molecular functions. But there are no tools to...system suitable for imaging signals from in small animals on the standard radiation therapy tools. (3) To evaluate the limits on structural , metabolic

Echographic imaging of tumoral cells through novel nanosystems for image diagnosis

PubMed Central

Di Paola, Marco; Chiriacò, Fernanda; Soloperto, Giulia; Conversano, Francesco; Casciaro, Sergio

2014-01-01

Since the recognition of disease molecular basis, it has become clear that the keystone moments of medical practice, namely early diagnosis, appropriate therapeutic treatment and patient follow-up, must be approached at a molecular level. These objectives will be in the near future more effectively achievable thanks to the impressive developments in nanotechnologies and their applications to the biomedical field, starting-up the nanomedicine era. The continuous advances in the development of biocompatible smart nanomaterials, in particular, will be crucial in several aspects of medicine. In fact, the possibility of manufacturing nanoparticle contrast agents that can be selectively targeted to specific pathological cells has extended molecular imaging applications to non-ionizing techniques and, at the same time, has made reachable the perspective of combining highly accurate diagnoses and personalized therapies in a single theranostic intervention. Main developing applications of nanosized theranostic agents include targeted molecular imaging, controlled drug release, therapeutic monitoring, guidance of radiation-based treatments and surgical interventions. Here we will review the most recent findings in nanoparticles contrast agents and their applications in the field of cancer molecular imaging employing non-ionizing techniques and disease-specific contrast agents, with special focus on recent findings on those nanomaterials particularly promising for ultrasound molecular imaging and simultaneous treatment of cancer. PMID:25071886

Intraductal Tubulopapillary Neoplasm of the Pancreas: An Update From a Pathologist's Perspective.

PubMed

Rooney, Sarah L; Shi, Jiaqi

2016-10-01

-Intraductal tubulopapillary neoplasm (ITPN) is a rare intraductal epithelial neoplasm of the pancreas recently recognized as a distinct entity by the World Health Organization classification in 2010. It is defined as an intraductal, grossly visible, tubule-forming epithelial neoplasm with high-grade dysplasia and ductal differentiation without overt production of mucin. The diagnosis can be challenging owing to morphologic overlap with other intraductal lesions and its rarity. While recent advances in molecular genetic studies of ITPN have provided new tools to facilitate clinical diagnosis, the limited number of cases has yielded limited follow-up data to guide management. -To provide a clinical, pathologic, and molecular update on ITPN with respect to clinical presentation, imaging findings, histopathologic features, differential diagnosis, biological behavior, molecular characteristics, and treatment options. -Analysis of the pertinent literature (PubMed) and authors' research and clinical practice experience based on institutional and consultation materials. -Clinical presentation, imaging findings, histopathology, immunohistochemistry studies, molecular characteristics, prognosis, and treatment options of ITPN are reviewed. Important differential diagnoses with other intraductal neoplasms of the pancreas-especially intraductal papillary mucinous neoplasm-using histopathologic, molecular, and immunohistochemical studies, are discussed. Despite the recent progress, more studies are necessary to assess the biology and genetics of ITPN for a better understanding of the prognostic factors and treatment options.

Spatial and molecular resolution of diffuse malignant mesothelioma heterogeneity by integrating label-free FTIR imaging, laser capture microdissection and proteomics

NASA Astrophysics Data System (ADS)

Großerueschkamp, Frederik; Bracht, Thilo; Diehl, Hanna C.; Kuepper, Claus; Ahrens, Maike; Kallenbach-Thieltges, Angela; Mosig, Axel; Eisenacher, Martin; Marcus, Katrin; Behrens, Thomas; Brüning, Thomas; Theegarten, Dirk; Sitek, Barbara; Gerwert, Klaus

2017-03-01

Diffuse malignant mesothelioma (DMM) is a heterogeneous malignant neoplasia manifesting with three subtypes: epithelioid, sarcomatoid and biphasic. DMM exhibit a high degree of spatial heterogeneity that complicates a thorough understanding of the underlying different molecular processes in each subtype. We present a novel approach to spatially resolve the heterogeneity of a tumour in a label-free manner by integrating FTIR imaging and laser capture microdissection (LCM). Subsequent proteome analysis of the dissected homogenous samples provides in addition molecular resolution. FTIR imaging resolves tumour subtypes within tissue thin-sections in an automated and label-free manner with accuracy of about 85% for DMM subtypes. Even in highly heterogeneous tissue structures, our label-free approach can identify small regions of interest, which can be dissected as homogeneous samples using LCM. Subsequent proteome analysis provides a location specific molecular characterization. Applied to DMM subtypes, we identify 142 differentially expressed proteins, including five protein biomarkers commonly used in DMM immunohistochemistry panels. Thus, FTIR imaging resolves not only morphological alteration within tissue but it resolves even alterations at the level of single proteins in tumour subtypes. Our fully automated workflow FTIR-guided LCM opens new avenues collecting homogeneous samples for precise and predictive biomarkers from omics studies.

Spatial and molecular resolution of diffuse malignant mesothelioma heterogeneity by integrating label-free FTIR imaging, laser capture microdissection and proteomics.

PubMed

Großerueschkamp, Frederik; Bracht, Thilo; Diehl, Hanna C; Kuepper, Claus; Ahrens, Maike; Kallenbach-Thieltges, Angela; Mosig, Axel; Eisenacher, Martin; Marcus, Katrin; Behrens, Thomas; Brüning, Thomas; Theegarten, Dirk; Sitek, Barbara; Gerwert, Klaus

2017-03-30

Diffuse malignant mesothelioma (DMM) is a heterogeneous malignant neoplasia manifesting with three subtypes: epithelioid, sarcomatoid and biphasic. DMM exhibit a high degree of spatial heterogeneity that complicates a thorough understanding of the underlying different molecular processes in each subtype. We present a novel approach to spatially resolve the heterogeneity of a tumour in a label-free manner by integrating FTIR imaging and laser capture microdissection (LCM). Subsequent proteome analysis of the dissected homogenous samples provides in addition molecular resolution. FTIR imaging resolves tumour subtypes within tissue thin-sections in an automated and label-free manner with accuracy of about 85% for DMM subtypes. Even in highly heterogeneous tissue structures, our label-free approach can identify small regions of interest, which can be dissected as homogeneous samples using LCM. Subsequent proteome analysis provides a location specific molecular characterization. Applied to DMM subtypes, we identify 142 differentially expressed proteins, including five protein biomarkers commonly used in DMM immunohistochemistry panels. Thus, FTIR imaging resolves not only morphological alteration within tissue but it resolves even alterations at the level of single proteins in tumour subtypes. Our fully automated workflow FTIR-guided LCM opens new avenues collecting homogeneous samples for precise and predictive biomarkers from omics studies.

Sample Preparation for Mass Spectrometry Imaging of Plant Tissues: A Review

PubMed Central

Dong, Yonghui; Li, Bin; Malitsky, Sergey; Rogachev, Ilana; Aharoni, Asaph; Kaftan, Filip; Svatoš, Aleš; Franceschi, Pietro

2016-01-01

Mass spectrometry imaging (MSI) is a mass spectrometry based molecular ion imaging technique. It provides the means for ascertaining the spatial distribution of a large variety of analytes directly on tissue sample surfaces without any labeling or staining agents. These advantages make it an attractive molecular histology tool in medical, pharmaceutical, and biological research. Likewise, MSI has started gaining popularity in plant sciences; yet, information regarding sample preparation methods for plant tissues is still limited. Sample preparation is a crucial step that is directly associated with the quality and authenticity of the imaging results, it therefore demands in-depth studies based on the characteristics of plant samples. In this review, a sample preparation pipeline is discussed in detail and illustrated through selected practical examples. In particular, special concerns regarding sample preparation for plant imaging are critically evaluated. Finally, the applications of MSI techniques in plants are reviewed according to different classes of plant metabolites. PMID:26904042

Measuring changes in chemistry, composition, and molecular structure within hair fibers by infrared and Raman spectroscopic imaging.

PubMed

Zhang, Guojin; Senak, Laurence; Moore, David J

2011-05-01

Spatially resolved infrared (IR) and Raman images are acquired from human hair cross sections or intact hair fibers. The full informational content of these spectra are spatially correlated to hair chemistry, anatomy, and structural organization through univariate and multivariate data analysis. Specific IR and Raman images from untreated human hair describing the spatial dependence of lipid and protein distribution, protein secondary structure, lipid chain conformational order, and distribution of disulfide cross-links in hair protein are presented in this study. Factor analysis of the image plane acquired with IR microscopy in hair sections, permits delineation of specific micro-regions within the hair. These data indicate that both IR and Raman imaging of molecular structural changes in a specific region of hair will prove to be valuable tools in the understanding of hair structure, physiology, and the effect of various stresses upon its integrity.

Molecular Imaging of Influenza and Other Emerging Respiratory Viral Infections

PubMed Central

Lawler, James; Paragas, Jason; Jahrling, Peter B.; Mollura, Daniel J.

2011-01-01

Research on the pathogenesis and therapy of influenza and other emerging respiratory viral infections would be aided by methods that directly visualize pathophysiologic processes in patients and laboratory animals. At present, imaging of diseases, such as swine-origin H1N1 influenza, is largely restricted to chest radiograph and computed tomography (CT), which can detect pulmonary structural changes in severely ill patients but are more limited in characterizing the early stages of illness, differentiating inflammation from infection or tracking immune responses. In contrast, imaging modalities, such as positron emission tomography, single photon emission CT, magnetic resonance imaging, and bioluminescence imaging, which have become useful tools for investigating the pathogenesis of a range of disease processes, could be used to advance in vivo studies of respiratory viral infections in patients and animals. Molecular techniques might also be used to identify novel biomarkers of disease progression and to evaluate new therapies. PMID:21422476

Molecular imaging to track Parkinson's disease and atypical parkinsonisms: New imaging frontiers.

PubMed

Strafella, Antonio P; Bohnen, Nicolaas I; Perlmutter, Joel S; Eidelberg, David; Pavese, Nicola; Van Eimeren, Thilo; Piccini, Paola; Politis, Marios; Thobois, Stephane; Ceravolo, Roberto; Higuchi, Makoto; Kaasinen, Valtteri; Masellis, Mario; Peralta, M Cecilia; Obeso, Ignacio; Pineda-Pardo, Jose Ángel; Cilia, Roberto; Ballanger, Benedicte; Niethammer, Martin; Stoessl, Jon A

2017-02-01

Molecular imaging has proven to be a powerful tool for investigation of parkinsonian disorders. One current challenge is to identify biomarkers of early changes that may predict the clinical trajectory of parkinsonian disorders. Exciting new tracer developments hold the potential for in vivo markers of underlying pathology. Herein, we provide an overview of molecular imaging advances and how these approaches help us to understand PD and atypical parkinsonisms. © 2016 International Parkinson and Movement Disorder Society. © 2016 International Parkinson and Movement Disorder Society.

Molecular SPECT Imaging: An Overview

PubMed Central

Khalil, Magdy M.; Tremoleda, Jordi L.; Bayomy, Tamer B.; Gsell, Willy

2011-01-01

Molecular imaging has witnessed a tremendous change over the last decade. Growing interest and emphasis are placed on this specialized technology represented by developing new scanners, pharmaceutical drugs, diagnostic agents, new therapeutic regimens, and ultimately, significant improvement of patient health care. Single photon emission computed tomography (SPECT) and positron emission tomography (PET) have their signature on paving the way to molecular diagnostics and personalized medicine. The former will be the topic of the current paper where the authors address the current position of the molecular SPECT imaging among other imaging techniques, describing strengths and weaknesses, differences between SPECT and PET, and focusing on different SPECT designs and detection systems. Radiopharmaceutical compounds of clinical as well-preclinical interest have also been reviewed. Moreover, the last section covers several application, of μSPECT imaging in many areas of disease detection and diagnosis. PMID:21603240

A study of MRI-guided diffuse fluorescence molecular tomography for monitoring PDT effects in pancreas cancer

NASA Astrophysics Data System (ADS)

Samkoe, Kimberley S.; Davis, Scott C.; Srinivasan, Subhadra; O'Hara, Julia A.; Hasan, Tayyaba; Pogue, Brian W.

2009-06-01

Over the last several decades little progress has been made in the therapy and treatment monitoring of pancreas adenocarcinoma, a devastating and aggressive form of cancer that has a 5-year patient survival rate of 3%. Currently, investigations for the use of interstitial Verteporfin photodynamic therapy (PDT) are being undertaken in both orthotopic xenograft mouse models and in human clinical trials. In the mouse models, magnetic resonance (MR) imaging has been used as a measure of surrogate response to Verteporfin PDT; however, MR imaging alone lacks the molecular information required to assess the metabolic function and growth rates of the tumor immediately after treatment. We propose the implementation of MR-guided fluorescence tomography in conjunction with a fluorescently labeled (IR-Dye 800 CW, LI-COR) epidermal growth factor (EGF) as a molecular measure of surrogate response. To demonstrate the effectiveness of MR-guided diffuse fluorescence tomography for molecular imaging, we have used the AsPC-1 (+EGFR) human pancreatic adenocarcinoma in an orthotopic mouse model. EGF IRDye 800CW was injected 48 hours prior to imaging. MR image sequences were collected simultaneously with the fluorescence data using a MR-coupled diffuse optical tomography system. Image reconstruction was performed multiple times with varying abdominal organ segmentation in order to obtain a optimal tomographic image. It is shown that diffuse fluorescence tomography of the orthotopic pancreas model is feasible, with consideration of confounding fluorescence signals from the multiple organs and tissues surrounding the pancreas. MR-guided diffuse fluorescence tomography will be used to monitor EGF response after photodynamic therapy. Additionally, it provide the opportunity to individualize subsequent therapies based on response to PDT as well as to evaluate the success of combination therapies, such as PDT with chemotherapy, antibody therapy or even radiation.

Clinical Amyloid Imaging.

PubMed

Mallik, Atul; Drzezga, Alex; Minoshima, Satoshi

2017-01-01

Amyloid plaques, along with neurofibrillary tangles, are a neuropathologic hallmark of Alzheimer disease (AD). Recently, amyloid PET radiotracers have been developed and approved for clinical use in the evaluation of suspected neurodegenerative disorders. In both research and clinical settings, amyloid PET imaging has provided important diagnostic and prognostic information for the management of patients with possible AD, mild cognitive impairment (MCI), and other challenging diagnostic presentations. Although the overall impact of amyloid imaging is still being evaluated, the Society of Nuclear Medicine and Molecular Imaging and Alzheimer's Association Amyloid Imaging Task Force have created appropriate use criteria for the standard clinical use of amyloid PET imaging. By the appropriate use criteria, amyloid imaging is appropriate for patients with (1) persistent or unexplained MCI, (2) AD as a possible but still uncertain diagnosis after expert evaluation and (3) atypically early-age-onset progressive dementia. To better understand the clinical and economic effect of amyloid imaging, the Imaging Dementia-Evidence for Amyloid Scanning (IDEAS) study is an ongoing large multicenter study in the United States, which is evaluating how amyloid imaging affects diagnosis, management, and outcomes for cognitively impaired patients who cannot be completely evaluated by clinical assessment alone. Multiple other large-scale studies are evaluating the prognostic role of amyloid PET imaging for predicting MCI progression to AD in general and high-risk populations. At the same time, amyloid imaging is an important tool for evaluating potential disease-modifying therapies for AD. Overall, the increased use of amyloid PET imaging has led to a better understanding of the strengths and limitations of this imaging modality and how it may best be used with other clinical, molecular, and imaging assessment techniques for the diagnosis and management of neurodegenerative disorders. Copyright © 2017 Elsevier Inc. All rights reserved.

Cell biochemistry studied by single-molecule imaging.

PubMed

Mashanov, G I; Nenasheva, T A; Peckham, M; Molloy, J E

2006-11-01

Over the last decade, there have been remarkable developments in live-cell imaging. We can now readily observe individual protein molecules within living cells and this should contribute to a systems level understanding of biological pathways. Direct observation of single fluorophores enables several types of molecular information to be gathered. Temporal and spatial trajectories enable diffusion constants and binding kinetics to be deduced, while analyses of fluorescence lifetime, intensity, polarization or spectra give chemical and conformational information about molecules in their cellular context. By recording the spatial trajectories of pairs of interacting molecules, formation of larger molecular complexes can be studied. In the future, multicolour and multiparameter imaging of single molecules in live cells will be a powerful analytical tool for systems biology. Here, we discuss measurements of single-molecule mobility and residency at the plasma membrane of live cells. Analysis of diffusional paths at the plasma membrane gives information about its physical properties and measurement of temporal trajectories enables rates of binding and dissociation to be derived. Meanwhile, close scrutiny of individual fluorophore trajectories enables ideas about molecular dimerization and oligomerization related to function to be tested directly.

Toward tunable doping in graphene FETs by molecular self-assembled monolayers

NASA Astrophysics Data System (ADS)

Li, Bing; Klekachev, Alexander V.; Cantoro, Mirco; Huyghebaert, Cedric; Stesmans, André; Asselberghs, Inge; de Gendt, Stefan; de Feyter, Steven

2013-09-01

In this paper, we report the formation of self-assembled monolayers (SAMs) of oleylamine (OA) on highly oriented pyrolytic graphite (HOPG) and graphene surfaces and demonstrate the potential of using such organic SAMs to tailor the electronic properties of graphene. Molecular resolution Atomic Force Microscopy (AFM) and Scanning Tunneling Microscopy (STM) images reveal the detailed molecular ordering. The electrical measurements show that OA strongly interacts with graphene leading to n-doping effects in graphene devices. The doping levels are tunable by varying the OA deposition conditions. Importantly, neither hole nor electron mobilities are decreased by the OA modification. As a benefit from this noncovalent modification strategy, the pristine characteristics of the device are recoverable upon OA removal. From this study, one can envision the possibility to correlate the graphene-based device performance with the molecular structure and supramolecular ordering of the organic dopant.In this paper, we report the formation of self-assembled monolayers (SAMs) of oleylamine (OA) on highly oriented pyrolytic graphite (HOPG) and graphene surfaces and demonstrate the potential of using such organic SAMs to tailor the electronic properties of graphene. Molecular resolution Atomic Force Microscopy (AFM) and Scanning Tunneling Microscopy (STM) images reveal the detailed molecular ordering. The electrical measurements show that OA strongly interacts with graphene leading to n-doping effects in graphene devices. The doping levels are tunable by varying the OA deposition conditions. Importantly, neither hole nor electron mobilities are decreased by the OA modification. As a benefit from this noncovalent modification strategy, the pristine characteristics of the device are recoverable upon OA removal. From this study, one can envision the possibility to correlate the graphene-based device performance with the molecular structure and supramolecular ordering of the organic dopant. Electronic supplementary information (ESI) available: AFM images of self-assembled monolayers of OA on HOPG; AFM height image of the graphene surface on a SiC substrate; high resolution STM image of a self-assembled monolayer of OA on HOPG; transfer curves of a graphene FET with and without baking steps; transfer curves of a graphene FET under high vacuum conditions; transfer curves of a graphene FET and its Raman response before and after OA treatment; transfer curves of a graphene FET before and after rinsing with n-hexane. See DOI: 10.1039/c3nr01255g

Masses, luminosities and dynamics of galactic molecular clouds

NASA Technical Reports Server (NTRS)

Solomon, P. M.; Rivolo, A. R.; Mooney, T. J.; Barrett, J. W.; Sage, L. J.

1987-01-01

Star formation in galaxies takes place in molecular clouds and the Milky Way is the only galaxy in which it is possible to resolve and study the physical properties and star formation activity of individual clouds. The masses, luminosities, dynamics, and distribution of molecular clouds, primarily giant molecular clouds in the Milky Way are described and analyzed. The observational data sets are the Massachusetts-Stony Brook CO Galactic Plane Survey and the IRAS far IR images. The molecular mass and infrared luminosities of glactic clouds are then compared with the molecular mass and infrared luminosities of external galaxies.

Detection of early primary colorectal cancer with upconversion luminescent NP-based molecular probes

NASA Astrophysics Data System (ADS)

Liu, Chunyan; Qi, Yifei; Qiao, Ruirui; Hou, Yi; Chan, Kaying; Li, Ziqian; Huang, Jiayi; Jing, Lihong; Du, Jun; Gao, Mingyuan

2016-06-01

Early detection and diagnosis of cancers is extremely beneficial for improving the survival rate of cancer patients and molecular imaging techniques are believed to be relevant for offering clinical solutions. Towards early cancer detection, we developed a primary animal colorectal cancer model and constructed a tumor-specific imaging probe by using biocompatible NaGdF4:Yb,Er@NaGdF4 upconversion luminescent NPs for establishing a sensitive early tumor imaging method. The primary animal tumor model, which can better mimic the human colorectal cancer, was built upon continual administration of 1,2-dimethylhydrazine in Kunming mice and the tumor development was carefully monitored through histopathological and immunohistochemical analyses to reveal the pathophysiological processes and molecular features of the cancer microenvironment. The upconversion imaging probe was constructed through covalent coupling of PEGylated core-shell NPs with folic acid whose receptor is highly expressed in the primary tumors. Upon 980 nm laser excitation, the primary colorectal tumors in the complex abdominal environment were sensitively imaged owing to the ultralow background of the upconversion luminescence and the high tumor-targeting specificity of the nanoprobe. We believe that the current studies provide a highly effective and potential approach for early colorectal cancer diagnosis and tumor surgical navigation.Early detection and diagnosis of cancers is extremely beneficial for improving the survival rate of cancer patients and molecular imaging techniques are believed to be relevant for offering clinical solutions. Towards early cancer detection, we developed a primary animal colorectal cancer model and constructed a tumor-specific imaging probe by using biocompatible NaGdF4:Yb,Er@NaGdF4 upconversion luminescent NPs for establishing a sensitive early tumor imaging method. The primary animal tumor model, which can better mimic the human colorectal cancer, was built upon continual administration of 1,2-dimethylhydrazine in Kunming mice and the tumor development was carefully monitored through histopathological and immunohistochemical analyses to reveal the pathophysiological processes and molecular features of the cancer microenvironment. The upconversion imaging probe was constructed through covalent coupling of PEGylated core-shell NPs with folic acid whose receptor is highly expressed in the primary tumors. Upon 980 nm laser excitation, the primary colorectal tumors in the complex abdominal environment were sensitively imaged owing to the ultralow background of the upconversion luminescence and the high tumor-targeting specificity of the nanoprobe. We believe that the current studies provide a highly effective and potential approach for early colorectal cancer diagnosis and tumor surgical navigation. Electronic supplementary information (ESI) available: (1) Molecular structure of Jeffamine-modified FA; (2) immunohistochemical analysis of FR expression in the colorectal tissue derived from mice treated with NaCl at different weeks; (3) biodistributions of probes of NP-FA and NP-IgG in the main organs of mice. See DOI: 10.1039/c5nr07858j

Quantitative real-time analysis of collective cancer invasion and dissemination

NASA Astrophysics Data System (ADS)

Ewald, Andrew J.

2015-05-01

A grand challenge in biology is to understand the cellular and molecular basis of tissue and organ level function in mammals. The ultimate goals of such efforts are to explain how organs arise in development from the coordinated actions of their constituent cells and to determine how molecularly regulated changes in cell behavior alter the structure and function of organs during disease processes. Two major barriers stand in the way of achieving these goals: the relative inaccessibility of cellular processes in mammals and the daunting complexity of the signaling environment inside an intact organ in vivo. To overcome these barriers, we have developed a suite of tissue isolation, three dimensional (3D) culture, genetic manipulation, nanobiomaterials, imaging, and molecular analysis techniques to enable the real-time study of cell biology within intact tissues in physiologically relevant 3D environments. This manuscript introduces the rationale for 3D culture, reviews challenges to optical imaging in these cultures, and identifies current limitations in the analysis of complex experimental designs that could be overcome with improved imaging, imaging analysis, and automated classification of the results of experimental interventions.

Colocalization of cellular nanostructure using confocal fluorescence and partial wave spectroscopy.

PubMed

Chandler, John E; Stypula-Cyrus, Yolanda; Almassalha, Luay; Bauer, Greta; Bowen, Leah; Subramanian, Hariharan; Szleifer, Igal; Backman, Vadim

2017-03-01

A new multimodal confocal microscope has been developed, which includes a parallel Partial Wave Spectroscopic (PWS) microscopy path. This combination of modalities allows molecular-specific sensing of nanoscale intracellular structure using fluorescent labels. Combining molecular specificity and sensitivity to nanoscale structure allows localization of nanostructural intracellular changes, which is critical for understanding the mechanisms of diseases such as cancer. To demonstrate the capabilities of this multimodal instrument, we imaged HeLa cells treated with valinomycin, a potassium ionophore that uncouples oxidative phosphorylation. Colocalization of fluorescence images of the nuclei (Hoechst 33342) and mitochondria (anti-mitochondria conjugated to Alexa Fluor 488) with PWS measurements allowed us to detect a significant decrease in nuclear nanoscale heterogeneity (Σ), while no significant change in Σ was observed at mitochondrial sites. In addition, application of the new multimodal imaging approach was demonstrated on human buccal samples prepared using a cancer screening protocol. These images demonstrate that nanoscale intracellular structure can be studied in healthy and diseased cells at molecular-specific sites. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Polymeric spatial resolution test patterns for mass spectrometry imaging using nano-thermal analysis with atomic force microscopy

DOE PAGES

Tai, Tamin; Kertesz, Vilmos; Lin, Ming -Wei; ...

2017-05-11

As the spatial resolution of mass spectrometry imaging technologies has begun to reach into the nanometer regime, finding readily available or easily made resolution reference materials has become particularly challenging for molecular imaging purposes. This study describes the fabrication, characterization and use of vertical line array polymeric spatial resolution test patterns for nano-thermal analysis/atomic force microscopy/mass spectrometry chemical imaging.

Polymeric spatial resolution test patterns for mass spectrometry imaging using nano-thermal analysis with atomic force microscopy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tai, Tamin; Kertesz, Vilmos; Lin, Ming -Wei

As the spatial resolution of mass spectrometry imaging technologies has begun to reach into the nanometer regime, finding readily available or easily made resolution reference materials has become particularly challenging for molecular imaging purposes. This study describes the fabrication, characterization and use of vertical line array polymeric spatial resolution test patterns for nano-thermal analysis/atomic force microscopy/mass spectrometry chemical imaging.

Molecular imaging of the biological effects of quercetin and quercetin-rich foods.

PubMed

Moskaug, Jan Øivind; Carlsen, Harald; Myhrstad, Mari; Blomhoff, Rune

2004-04-01

The human diet contains several thousands of organic plant molecules (i.e. phytochemicals), many of which have significant bioactivities. The specific physiological effects of these compounds are impossible to predict from in vitro studies using cell cultures and cell-free model systems. Nutrigenomics, which may be defined as the application of genomic tools to study the integrated effects of nutrients on gene regulation, however, holds great promise in increasing the understanding of how nutrients affect molecular events in an organism. Quercetin, a phytochemical belonging to the flavonoids, has antioxidant activities, inhibit protein kinases, inhibit DNA topoisomerases and regulate gene expression. The aim of the present review is to describe some of the many effects of quercetin, and how molecular imaging using transgenic reporter mice may serve as a tool to study the integrated influence of quercetin and other dietary phytochemicals on gene expression in vivo. We are using the bioluminescence emitted from firefly luciferase as the reporter since light originating from the inside of a cell or organism can be detected externally in an intact living organism. Molecular imaging using reporter models is therefore a unique technology to study the integrated effects of environmental insults and dietary substances on the influence of gene expression in disease development. We utilize these in vivo models to elucidate the role of various flavonoids, such as quercetin, for modulating gene expression related to oxidative stress and the antioxidant defence system.

MIiSR: Molecular Interactions in Super-Resolution Imaging Enables the Analysis of Protein Interactions, Dynamics and Formation of Multi-protein Structures.

PubMed

Caetano, Fabiana A; Dirk, Brennan S; Tam, Joshua H K; Cavanagh, P Craig; Goiko, Maria; Ferguson, Stephen S G; Pasternak, Stephen H; Dikeakos, Jimmy D; de Bruyn, John R; Heit, Bryan

2015-12-01

Our current understanding of the molecular mechanisms which regulate cellular processes such as vesicular trafficking has been enabled by conventional biochemical and microscopy techniques. However, these methods often obscure the heterogeneity of the cellular environment, thus precluding a quantitative assessment of the molecular interactions regulating these processes. Herein, we present Molecular Interactions in Super Resolution (MIiSR) software which provides quantitative analysis tools for use with super-resolution images. MIiSR combines multiple tools for analyzing intermolecular interactions, molecular clustering and image segmentation. These tools enable quantification, in the native environment of the cell, of molecular interactions and the formation of higher-order molecular complexes. The capabilities and limitations of these analytical tools are demonstrated using both modeled data and examples derived from the vesicular trafficking system, thereby providing an established and validated experimental workflow capable of quantitatively assessing molecular interactions and molecular complex formation within the heterogeneous environment of the cell.

Simultaneous and spectroscopic redox molecular imaging of multiple free radical intermediates using dynamic nuclear polarization-magnetic resonance imaging.

PubMed

Hyodo, Fuminori; Ito, Shinji; Yasukawa, Keiji; Kobayashi, Ryoma; Utsumi, Hideo

2014-08-05

Redox reactions that generate free radical intermediates are essential to metabolic processes. However, their intermediates can produce reactive oxygen species, which may promote diseases related to oxidative stress. We report here the use of dynamic nuclear polarization-magnetic resonance imaging (DNP-MRI) to conduct redox molecular imaging. Using DNP-MRI, we obtained simultaneous images of free radical intermediates generated from the coenzyme Q10 (CoQ10), flavin mononucleotide (FMN), and flavin adenine dinucleotide (FAD) involved in the mitochondrial electron transport chain as well as the radicals derived from vitamins E and K1. Each of these free radicals was imaged in real time in a phantom comprising a mixture of free radicals localized in either lipophilic or aqueous environments. Changing the frequency of electron spin resonance (ESR) irradiation also allowed each of the radical species to be distinguished in the spectroscopic images. This study is the first to report the spectroscopic DNP-MRI imaging of free radical intermediates that are derived from endogenous species involved in metabolic processes.

Association Between Imaging Characteristics and Different Molecular Subtypes of Breast Cancer.

PubMed

Wu, Mingxiang; Ma, Jie

2017-04-01

Breast cancer can be divided into four major molecular subtypes based on the expression of hormone receptor (estrogen receptor and progesterone receptor), human epidermal growth factor receptor 2, HER2 status, and molecular proliferation rate (Ki67). In this study, we sought to investigate the association between breast cancer subtype and radiological findings in the Chinese population. Medical records of 300 consecutive invasive breast cancer patients were reviewed from the database: the Breast Imaging Reporting and Data System. The imaging characteristics of the lesions were evaluated. The molecular subtypes of breast cancer were classified into four types: luminal A, luminal B, HER2 overexpressed (HER2), and basal-like breast cancer (BLBC). Univariate and multivariate logistic regression analyses were performed to assess the association between the subtype (dependent variable) and mammography or 15 magnetic resonance imaging (MRI) indicators (independent variables). Luminal A and B subtypes were commonly associated with "clustered calcification distribution," "nipple invasion," or "skin invasion" (P <0.05). The BLBC subtype was more commonly associated with "rim enhancement" and persistent inflow type enhancement in delayed phase (P <0.05). HER2 overexpressed cancers showed association with persistent enhancement in the delayed phase on MRI and "clustered calcification distribution" on mammography (P <0.05). Certain radiological features are strongly associated with the molecular subtype and hormone receptor status of breast tumor, which are potentially useful tools in the diagnosis and subtyping of breast cancer. Copyright © 2017 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.

Hyperspectral small animal fluorescence imaging: spectral selection imaging

NASA Astrophysics Data System (ADS)

Leavesley, Silas; Jiang, Yanan; Patsekin, Valery; Hall, Heidi; Vizard, Douglas; Robinson, J. Paul

2008-02-01

Molecular imaging is a rapidly growing area of research, fueled by needs in pharmaceutical drug-development for methods for high-throughput screening, pre-clinical and clinical screening for visualizing tumor growth and drug targeting, and a growing number of applications in the molecular biology fields. Small animal fluorescence imaging employs fluorescent probes to target molecular events in vivo, with a large number of molecular targeting probes readily available. The ease at which new targeting compounds can be developed, the short acquisition times, and the low cost (compared to microCT, MRI, or PET) makes fluorescence imaging attractive. However, small animal fluorescence imaging suffers from high optical scattering, absorption, and autofluorescence. Much of these problems can be overcome through multispectral imaging techniques, which collect images at different fluorescence emission wavelengths, followed by analysis, classification, and spectral deconvolution methods to isolate signals from fluorescence emission. We present an alternative to the current method, using hyperspectral excitation scanning (spectral selection imaging), a technique that allows excitation at any wavelength in the visible and near-infrared wavelength range. In many cases, excitation imaging may be more effective at identifying specific fluorescence signals because of the higher complexity of the fluorophore excitation spectrum. Because the excitation is filtered and not the emission, the resolution limit and image shift imposed by acousto-optic tunable filters have no effect on imager performance. We will discuss design of the imager, optimizing the imager for use in small animal fluorescence imaging, and application of spectral analysis and classification methods for identifying specific fluorescence signals.

Molecular Imaging Probes for Positron Emission Tomography and Optical Imaging of Sentinel Lymph Node and Tumor

NASA Astrophysics Data System (ADS)

Qin, Zhengtao

Molecular imaging is visualizations and measurements of in vivo biological processes at the molecular or cellular level using specific imaging probes. As an emerging technology, biocompatible macromolecular or nanoparticle based targeted imaging probes have gained increasing popularities. Those complexes consist of a carrier, an imaging reporter, and a targeting ligand. The active targeting ability dramatically increases the specificity. And the multivalency effect may further reduce the dose while providing a decent signal. In this thesis, sentinel lymph node (SLN) mapping and cancer imaging are two research topics. The focus is to develop molecular imaging probes with high specificity and sensitivity, for Positron Emission Tomography (PET) and optical imaging. The objective of this thesis is to explore dextran radiopharmaceuticals and porous silicon nanoparticles based molecular imaging agents. Dextran polymers are excellent carriers to deliver imaging reporters or therapeutic agents due to its well established safety profile and oligosaccharide conjugation chemistry. There is also a wide selection of dextran polymers with different lengths. On the other hand, Silicon nanoparticles represent another class of biodegradable materials for imaging and drug delivery. The success in fluorescence lifetime imaging and enhancements of the immune activation potency was briefly discussed. Chapter 1 begins with an overview on current molecular imaging techniques and imaging probes. Chapter 2 presents a near-IR dye conjugated probe, IRDye 800CW-tilmanocept. Fluorophore density was optimized to generate the maximum brightness. It was labeled with 68Ga and 99mTc and in vivo SLN mapping was successfully performed in different animals, such as mice, rabbits, dogs and pigs. With 99mTc labeled IRDye 800CW-tilmanocept, chapter 3 introduces a two-day imaging protocol with a hand-held imager. Chapter 4 proposed a method to dual radiolabel the IRDye 800CW-tilmanocept with both 68Ga and 99mTc. Chapter 5 introduces a 68Ga metal chelating bioorthogonal tetrazine dextran probe for multistep imaging of a colon cancer. Chapter 6 presents the synthesis and in vivo evaluation of a Hepatocellular Carcinoma targeting PET probe 68Ga-Insulin-Dextran. Chapter 7 discusses a novel method to prepare silicon nanoparticles with great yield and size control. The last chapter 8 concludes all probes developed in this thesis and their clinical relevance.

Double agents and secret agents: the emerging fields of exogenous chemical exchange saturation transfer and T2-exchange magnetic resonance imaging contrast agents for molecular imaging.

PubMed

Daryaei, Iman; Pagel, Mark D

2015-01-01

Two relatively new types of exogenous magnetic resonance imaging contrast agents may provide greater impact for molecular imaging by providing greater specificity for detecting molecular imaging biomarkers. Exogenous chemical exchange saturation transfer (CEST) agents rely on the selective saturation of the magnetization of a proton on an agent, followed by chemical exchange of a proton from the agent to water. The selective detection of a biomarker-responsive CEST signal and an unresponsive CEST signal, followed by the ratiometric comparison of these signals, can improve biomarker specificity. We refer to this improvement as a "double-agent" approach to molecular imaging. Exogenous T 2 -exchange agents also rely on chemical exchange of protons between the agent and water, especially with an intermediate rate that lies between the slow exchange rates of CEST agents and the fast exchange rates of traditional T 1 and T 2 agents. Because of this intermediate exchange rate, these agents have been relatively unknown and have acted as "secret agents" in the contrast agent research field. This review exposes these secret agents and describes the merits of double agents through examples of exogenous agents that detect enzyme activity, nucleic acids and gene expression, metabolites, ions, redox state, temperature, and pH. Future directions are also provided for improving both types of contrast agents for improved molecular imaging and clinical translation. Therefore, this review provides an overview of two new types of exogenous contrast agents that are becoming useful tools within the armamentarium of molecular imaging.

Double agents and secret agents: the emerging fields of exogenous chemical exchange saturation transfer and T2-exchange magnetic resonance imaging contrast agents for molecular imaging

PubMed Central

Daryaei, Iman; Pagel, Mark D

2016-01-01

Two relatively new types of exogenous magnetic resonance imaging contrast agents may provide greater impact for molecular imaging by providing greater specificity for detecting molecular imaging biomarkers. Exogenous chemical exchange saturation transfer (CEST) agents rely on the selective saturation of the magnetization of a proton on an agent, followed by chemical exchange of a proton from the agent to water. The selective detection of a biomarker-responsive CEST signal and an unresponsive CEST signal, followed by the ratiometric comparison of these signals, can improve biomarker specificity. We refer to this improvement as a “double-agent” approach to molecular imaging. Exogenous T2-exchange agents also rely on chemical exchange of protons between the agent and water, especially with an intermediate rate that lies between the slow exchange rates of CEST agents and the fast exchange rates of traditional T1 and T2 agents. Because of this intermediate exchange rate, these agents have been relatively unknown and have acted as “secret agents” in the contrast agent research field. This review exposes these secret agents and describes the merits of double agents through examples of exogenous agents that detect enzyme activity, nucleic acids and gene expression, metabolites, ions, redox state, temperature, and pH. Future directions are also provided for improving both types of contrast agents for improved molecular imaging and clinical translation. Therefore, this review provides an overview of two new types of exogenous contrast agents that are becoming useful tools within the armamentarium of molecular imaging. PMID:27747191

Novel iodinated tracers, MIBG and BMIPP, for nuclear cardiology.

PubMed

Tamaki, Nagara; Yoshinaga, Keiichiro

2011-02-01

With the rapid growth of molecular biology, in vivo imaging of such molecular process (i.e., molecular imaging) has been well developed. The molecular imaging has been focused on justifying advanced treatments and for assessing the treatment effects. Most of molecular imaging has been developed using PET camera and suitable PET radiopharmaceuticals. However, this technique cannot be widely available and we need alternative approach. ¹²³I-labeled compounds have been also suitable for molecular imaging using single-photon computed tomography (SPECT) ¹²³I-labeled meta-iodobenzylguanidine (MIBG) has been used for assessing severity of heart failure and prognosis. In addition, it has a potential role to predict fatal arrhythmia, particularly for those who had and are planned to receive implantable cardioverter-defibrillator treatment. ¹²³I-beta-methyl-iodophenylpentadecanoic acid (BMIPP) plays an important role for identifying ischemia at rest, based on the unique capability to represent persistent metabolic alteration after recovery of ischemia, so called ischemic memory. Since BMIPP abnormalities may represent severe ischemia or jeopardized myocardium, it may permit risk analysis in CAD patients, particularly for those with chronic kidney disease and/or hemodialysis patients. This review will discuss about recent development of these important iodinated compounds.

Novel iodinated tracers, MIBG and BMIPP, for nuclear cardiology

PubMed Central

Yoshinaga, Keiichiro

2010-01-01

With the rapid growth of molecular biology, in vivo imaging of such molecular process (i.e., molecular imaging) has been well developed. The molecular imaging has been focused on justifying advanced treatments and for assessing the treatment effects. Most of molecular imaging has been developed using PET camera and suitable PET radiopharmaceuticals. However, this technique cannot be widely available and we need alternative approach. 123I-labeled compounds have been also suitable for molecular imaging using single-photon computed tomography (SPECT) 123I-labeled meta-iodobenzylguanidine (MIBG) has been used for assessing severity of heart failure and prognosis. In addition, it has a potential role to predict fatal arrhythmia, particularly for those who had and are planned to receive implantable cardioverter-defibrillator treatment. 123I-beta-methyl-iodophenylpentadecanoic acid (BMIPP) plays an important role for identifying ischemia at rest, based on the unique capability to represent persistent metabolic alteration after recovery of ischemia, so called ischemic memory. Since BMIPP abnormalities may represent severe ischemia or jeopardized myocardium, it may permit risk analysis in CAD patients, particularly for those with chronic kidney disease and/or hemodialysis patients. This review will discuss about recent development of these important iodinated compounds. PMID:21082300

Earle K. Plyler Prize Lecture: The Three Pillars of Ultrafast Molecular Science - Time, Phase, Intensity

NASA Astrophysics Data System (ADS)

Stolow, Albert

We discuss the probing and control of molecular wavepacket dynamics in the context of three main `pillars' of light-matter interaction: time, phase, intensity. Time: Using short, coherent laser pulses and perturbative matter-field interactions, we study molecular wavepackets with a focus on the ultrafast non-Born-Oppenheimer dynamics, that is, the coupling of electronic and nuclear motions. Time-Resolved Photoelectron Spectroscopy (TRPES) is a powerful ultrafast probe of these processes in polyatomic molecules because it is sensitive both electronic and vibrational dynamics. Ideally, one would like to observe these ultrafast processes from the molecule's point of view - the Molecular Frame - thereby avoiding loss of information due to orientational averaging. This can be achieved by Time-Resolved Coincidence Imaging Spectroscopy (TRCIS) which images 3D recoil vectors of both photofragments and photoelectrons, in coincidence and as a function of time, permitting direct Molecular Frame imaging of valence electronic dynamics during a molecular dynamics. Phase: Using intermediate strength non-perturbative interactions, we apply the second order (polarizability) Non-Resonant Dynamic Stark Effect (NRDSE) to control molecular dynamics without any net absorption of light. NRDSE is also the interaction underlying molecular alignment and applies to field-free 1D of linear molecules and field-free 3D alignment of general (asymmetric) molecules. Using laser alignment, we can transiently fix a molecule in space, yielding a more general approach to direct Molecular Frame imaging of valence electronic dynamics during a chemical reaction. Intensity: In strong (ionizing) laser fields, a new laser-matter physics emerges for polyatomic systems wherein both the single active electron picture and the adiabatic electron response, both implicit in the standard 3-step models, can fail dramatically. This has important consequences for all attosecond strong field spectroscopies of polyatomic molecules, including high harmonic generation (HHG). We discuss an experimental method, Channel-Resolved Above Threshold Ionization (CRATI), which directly unveils the electronic channels participating in the attosecond molecular strong field ionization response [10]. This work was supported by the National Research Council of Canada and the Natural Sciences & Engineering Research Council.

Histopathology mapping of biochemical changes in myocardial infarction by Fourier transform infrared spectral imaging.

PubMed

Yang, Tian T; Weng, Shi F; Zheng, Na; Pan, Qing H; Cao, Hong L; Liu, Liang; Zhang, Hai D; Mu, Da W

2011-04-15

Fourier transform infrared (FTIR) imaging and microspectroscopy have been extensively applied in the identification and investigation of both healthy and diseased tissues. FTIR imaging can be used to determine the biodistribution of several molecules of interest (carbohydrates, lipids, proteins) for tissue analysis, without the need for prior staining of these tissues. Molecular structure data, such as protein secondary structure and collagen triple helix exhibits, can also be obtained from the same analysis. Thus, several histopathological lesions, for example myocardial infarction, can be identified from FTIR-analyzed tissue images, the latter which can allow for more accurate discrimination between healthy tissues and pathological lesions. Accordingly, we propose FTIR imaging as a new tool integrating both molecular and histopathological assessment to investigate the degree of pathological changes in tissues. In this study, myocardial infarction is presented as an illustrative example of the wide potential of FTIR imaging for biomedical applications. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Histomolecular interpretation of pleomorphic adenomas of the salivary gland by matrix-assisted laser desorption ionization imaging and spatial segmentation.

PubMed

Ernst, Günther; Guntinas-Lichius, Orlando; Hauberg-Lotte, Lena; Trede, Dennis; Becker, Michael; Alexandrov, Theodore; von Eggeling, Ferdinand

2015-07-01

Despite efforts in localization of key proteins using immunohistochemistry, the complex proteomic composition of pleomorphic adenomas has not yet been characterized. Matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI imaging) allows label-free and spatially resolved detection of hundreds of proteins directly from tissue sections and of histomorphological regions by finding colocalized molecular signals. Spatial segmentation of MALDI imaging data is an algorithmic method for finding regions of similar proteomic composition as functionally similar regions. We investigated 2 pleomorphic adenomas by applying spatial segmentation to the MALDI imaging data of tissue sections. The spatial segmentation subdivided the tissue in a good accordance with the tissue histology. Numerous molecular signals colocalized with histologically defined tissue regions were found. Our study highlights the cellular transdifferentiation within the pleomorphic adenoma. It could be shown that spatial segmentation of MALDI imaging data is a promising approach in the emerging field of digital histological analysis and characterization of tumors. © 2014 Wiley Periodicals, Inc.

Polarized x-ray excitation for scatter reduction in x-ray fluorescence computed tomography.

PubMed

Vernekohl, Don; Tzoumas, Stratis; Zhao, Wei; Xing, Lei

2018-05-25

X-ray fluorescence computer tomography (XFCT) is a new molecular imaging modality which uses x-ray excitation to stimulate the emission of fluorescent photons in high atomic number contrast agents. Scatter contamination is one of the main challenges in XFCT imaging which limits the molecular sensitivity. When polarized x rays are used, it is possible to reduce the scatter contamination significantly by placing detectors perpendicular to the polarization direction. This study quantifies scatter contamination for polarized and unpolarized x-ray excitation and determines the advantages of scatter reduction. The amount of scatter in preclinical XFCT is quantified in Monte Carlo simulations. The fluorescent x rays are emitted isotropically, while scattered x rays propagate in polarization direction. The magnitude of scatter contamination is studied in XFCT simulations of a mouse phantom. In this study, the contrast agent gold is examined as an example, but a scatter reduction from polarized excitation is also expected for other elements. The scatter reduction capability is examined for different polarization intensities with a monoenergetic x-ray excitation energy of 82 keV. The study evaluates two different geometrical shapes of CZT detectors which are modeled with an energy resolution of 1 keV FWHM at an x-ray energy of 80 keV. Benefits of a detector placement perpendicular to the polarization direction are shown in iterative and analytic image reconstruction including scatter correction. The contrast to noise ratio (CNR) and the normalized mean square error (NMSE) are analyzed and compared for the reconstructed images. A substantial scatter reduction for common detector sizes was achieved for 100% and 80% linear polarization while lower polarization intensities provide a decreased scatter reduction. By placing the detector perpendicular to the polarization direction, a scatter reduction by factor up to 5.5 can be achieved for common detector sizes. The image reconstruction showed that for a scatter magnitude decrease by a factor of 2.4, the molecular sensitivity could almost be doubled. Scatter reduction lowers the amount of noise in the projection datasets and reconstructed images which enhance molecular sensitivity at equal dose. The results support the use of linear polarized x rays to reduce scatter in XFCT imaging. © 2018 American Association of Physicists in Medicine.

Nanoparticle-facilitated functional and molecular imaging for the early detection of cancer

PubMed Central

Sivasubramanian, Maharajan; Hsia, Yu; Lo, Leu-Wei

2014-01-01

Cancer detection in its early stages is imperative for effective cancer treatment and patient survival. In recent years, biomedical imaging techniques, such as magnetic resonance imaging, computed tomography and ultrasound have been greatly developed and have served pivotal roles in clinical cancer management. Molecular imaging (MI) is a non-invasive imaging technique that monitors biological processes at the cellular and sub-cellular levels. To achieve these goals, MI uses targeted imaging agents that can bind targets of interest with high specificity and report on associated abnormalities, a task that cannot be performed by conventional imaging techniques. In this respect, MI holds great promise as a potential therapeutic tool for the early diagnosis of cancer. Nevertheless, the clinical applications of targeted imaging agents are limited due to their inability to overcome biological barriers inside the body. The use of nanoparticles has made it possible to overcome these limitations. Hence, nanoparticles have been the subject of a great deal of recent studies. Therefore, developing nanoparticle-based imaging agents that can target tumors via active or passive targeting mechanisms is desirable. This review focuses on the applications of various functionalized nanoparticle-based imaging agents used in MI for the early detection of cancer. PMID:25988156

Piezoelectric Composite Micromachined Multifrequency Transducers for High-Resolution, High-Contrast Ultrasound Imaging for Improved Prostate Cancer Assessment

DTIC Science & Technology

2015-08-01

prostate cancer. In the preliminary in-vitro study , imaging resolution, contrast to tissue ratio, and lesion detectability will be assessed relative to...a Siemens EV- 8C4 transrectal ultrasound probe. In the in-vivo study , molecular imaging and microvascular mapping will both be performed to assess...single element tests, years 2 and 3 have included progress towards the design of the final a dual frequency linear array. These studies included the

Preparation of a pure molecular quantum gas.

PubMed

Herbig, Jens; Kraemer, Tobias; Mark, Michael; Weber, Tino; Chin, Cheng; Nägerl, Hanns-Christoph; Grimm, Rudolf

2003-09-12

An ultracold molecular quantum gas is created by application of a magnetic field sweep across a Feshbach resonance to a Bose-Einstein condensate of cesium atoms. The ability to separate the molecules from the atoms permits direct imaging of the pure molecular sample. Magnetic levitation enables study of the dynamics of the ensemble on extended time scales. We measured ultralow expansion energies in the range of a few nanokelvin for a sample of 3000 molecules. Our observations are consistent with the presence of a macroscopic molecular matter wave.

Tandem Mass Spectrometry Imaging and in Situ Characterization of Bioactive Wood Metabolites in Amazonian Tree Species Sextonia rubra.

PubMed

Fu, Tingting; Touboul, David; Della-Negra, Serge; Houël, Emeline; Amusant, Nadine; Duplais, Christophe; Fisher, Gregory L; Brunelle, Alain

2018-06-19

Driven by a necessity for confident molecular identification at high spatial resolution, a new time-of-flight secondary ion mass spectrometry (TOF-SIMS) tandem mass spectrometry (tandem MS) imaging instrument has been recently developed. In this paper, the superior MS/MS spectrometry and imaging capability of this new tool is shown for natural product study. For the first time, via in situ analysis of the bioactive metabolites rubrynolide and rubrenolide in Amazonian tree species Sextonia rubra (Lauraceae), we were able both to analyze and to image by tandem MS the molecular products of natural biosynthesis. Despite the low abundance of the metabolites in the wood sample(s), efficient MS/MS analysis of these γ-lactone compounds was achieved, providing high confidence in the identification and localization. In addition, tandem MS imaging minimized the mass interferences and revealed specific localization of these metabolites primarily in the ray parenchyma cells but also in certain oil cells and, further, revealed the presence of previously unidentified γ-lactone, paving the way for future studies in biosynthesis.

Emerging diagnostic and therapeutic molecular imaging applications in vascular disease

PubMed Central

Eraso, Luis H; Reilly, Muredach P; Sehgal, Chandra; Mohler, Emile R

2013-01-01

Assessment of vascular disease has evolved from mere indirect and direct measurements of luminal stenosis to sophisticated imaging methods to depict millimeter structural changes of the vasculature. In the near future, the emergence of multimodal molecular imaging strategies may enable robust therapeutic and diagnostic (‘theragnostic’) approaches to vascular diseases that comprehensively consider structural, functional, biological and genomic characteristics of the disease in individualized risk assessment, early diagnosis and delivery of targeted interventions. This review presents a summary of recent preclinical and clinical developments in molecular imaging and theragnostic applications covering diverse atherosclerosis events such as endothelial activation, macrophage infammatory activity, plaque neovascularization and arterial thrombosis. The main focus is on molecular targets designed for imaging platforms commonly used in clinical medicine including magnetic resonance, computed tomography and positron emission tomography. A special emphasis is given to vascular ultrasound applications, considering the important role this imaging platform plays in the clinical and research practice of the vascular medicine specialty. PMID:21310769

Purification of a low molecular weight fucoidan for SPECT molecular imaging of myocardial infarction.

PubMed

Saboural, Pierre; Chaubet, Frédéric; Rouzet, Francois; Al-Shoukr, Faisal; Azzouna, Rana Ben; Bouchemal, Nadia; Picton, Luc; Louedec, Liliane; Maire, Murielle; Rolland, Lydia; Potier, Guy; Guludec, Dominique Le; Letourneur, Didier; Chauvierre, Cédric

2014-09-23

Fucoidans constitute a large family of sulfated polysaccharides with several biochemical properties. A commercial fucoidan from brown algae, containing low molecular weight polysaccharidic species constituted of l-fucose, uronic acids and sulfate groups, was simply treated here with calcium acetate solution. This treatment led to a purified fraction with a yield of 45%. The physicochemical characterizations of the purified fucoidan using colorimetric assay, MALLS, dRI, FT-IR, NMR, exhibited molecular weight distributions and chemical profiles similar for both fucoidans whereas the sulfate and l-fucose contents increased by 16% and 71%, respectively. The biodistribution study in rat of both compounds labeled with 99mTc evidenced a predominant renal elimination of the purified fucoidan, but the crude fucoidan was mainly retained in liver and spleen. In rat myocardial ischemia-reperfusion, we then demonstrated the better efficiency of the purified fucoidan. This purified sulfated polysaccharide appears promising for the development of molecular imaging in acute coronary syndrome.

Genetically Encoded Molecular Tension Probe for Tracing Protein-Protein Interactions in Mammalian Cells.

PubMed

Kim, Sung Bae; Nishihara, Ryo; Citterio, Daniel; Suzuki, Koji

2016-02-17

Optical imaging of protein-protein interactions (PPIs) facilitates comprehensive elucidation of intracellular molecular events. We demonstrate an optical measure for visualizing molecular tension triggered by any PPI in mammalian cells. Twenty-three kinds of candidate designs were fabricated, in which a full-length artificial luciferase (ALuc) was sandwiched between two model proteins of interest, e.g., FKBP and FRB. One of the designs greatly enhanced the bioluminescence in response to varying concentrations of rapamycin. It is confirmed with negative controls that the elevated bioluminescence is solely motivated from the molecular tension. The probe design was further modified toward eliminating the C-terminal end of ALuc and was found to improve signal-to-background ratios, named "a combinational probe". The utilities were elucidated with detailed substrate selectivity, bioluminescence imaging of live cells, and different PPI models. This study expands capabilities of luciferases as a tool for analyses of molecular dynamics and cell signaling in living subjects.

Purification of a Low Molecular Weight Fucoidan for SPECT Molecular Imaging of Myocardial Infarction

PubMed Central

Saboural, Pierre; Chaubet, Frédéric; Rouzet, Francois; Al-Shoukr, Faisal; Ben Azzouna, Rana; Bouchemal, Nadia; Picton, Luc; Louedec, Liliane; Maire, Murielle; Rolland, Lydia; Potier, Guy; Le Guludec, Dominique; Letourneur, Didier; Chauvierre, Cédric

2014-01-01

Fucoidans constitute a large family of sulfated polysaccharides with several biochemical properties. A commercial fucoidan from brown algae, containing low molecular weight polysaccharidic species constituted of l-fucose, uronic acids and sulfate groups, was simply treated here with calcium acetate solution. This treatment led to a purified fraction with a yield of 45%. The physicochemical characterizations of the purified fucoidan using colorimetric assay, MALLS, dRI, FT-IR, NMR, exhibited molecular weight distributions and chemical profiles similar for both fucoidans whereas the sulfate and l-fucose contents increased by 16% and 71%, respectively. The biodistribution study in rat of both compounds labeled with 99mTc evidenced a predominant renal elimination of the purified fucoidan, but the crude fucoidan was mainly retained in liver and spleen. In rat myocardial ischemia-reperfusion, we then demonstrated the better efficiency of the purified fucoidan. This purified sulfated polysaccharide appears promising for the development of molecular imaging in acute coronary syndrome. PMID:25251032

Nonlinear microrheology and molecular imaging to map microscale deformations of entangled DNA networks

NASA Astrophysics Data System (ADS)

Wu, Tsai-Chin; Anderson, Rae

We use active microrheology coupled to single-molecule fluorescence imaging to elucidate the microscale dynamics of entangled DNA. DNA naturally exists in a wide range of lengths and topologies, and is often confined in cell nucleui, forming highly concentrated and entangled biopolymer networks. Thus, DNA is the model polymer for understanding entangled polymer dynamics as well as the crowded environment of cells. These networks display complex viscoelastic properties that are not well understood, especially at the molecular-level and in response to nonlinear perturbations. Specifically, how microscopic stresses and strains propagate through entangled networks, and what molecular deformations lead to the network stress responses are unknown. To answer these important questions, we optically drive a microsphere through entangled DNA, perturbing the system far from equilibrium, while measuring the resistive force the DNA exerts on the bead during and after bead motion. We simultaneously image single fluorescent-labeled DNA molecules throughout the network to directly link the microscale stress response to molecular deformations. We characterize the deformation of the network from the molecular-level to the mesoscale, and map the stress propagation throughout the network. We further study the impact of DNA length (11 - 115 kbp) and topology (linear vs ring DNA) on deformation and propagation dynamics, exploring key nonlinear features such as tube dilation and power-law relaxation.

Molecular Imaging Probe Development using Microfluidics

PubMed Central

Liu, Kan; Wang, Ming-Wei; Lin, Wei-Yu; Phung, Duy Linh; Girgis, Mark D.; Wu, Anna M.; Tomlinson, James S.; Shen, Clifton K.-F.

2012-01-01

In this manuscript, we review the latest advancement of microfluidics in molecular imaging probe development. Due to increasing needs for medical imaging, high demand for many types of molecular imaging probes will have to be met by exploiting novel chemistry/radiochemistry and engineering technologies to improve the production and development of suitable probes. The microfluidic-based probe synthesis is currently attracting a great deal of interest because of their potential to deliver many advantages over conventional systems. Numerous chemical reactions have been successfully performed in micro-reactors and the results convincingly demonstrate with great benefits to aid synthetic procedures, such as purer products, higher yields, shorter reaction times compared to the corresponding batch/macroscale reactions, and more benign reaction conditions. Several ‘proof-of-principle’ examples of molecular imaging probe syntheses using microfluidics, along with basics of device architecture and operation, and their potential limitations are discussed here. PMID:22977436

Recent Advances in Cardiac Computed Tomography: Dual Energy, Spectral and Molecular CT Imaging

PubMed Central

Danad, Ibrahim; Fayad, Zahi A.; Willemink, Martin J.; Min, James K.

2015-01-01

Computed tomography (CT) evolved into a powerful diagnostic tool and it is impossible to imagine current clinical practice without CT imaging. Due to its widespread availability, ease of clinical application, superb sensitivity for detection of CAD, and non-invasive nature, CT has become a valuable tool within the armamentarium of the cardiologist. In the last few years, numerous technological advances in CT have occurred—including dual energy CT (DECT), spectral CT and CT-based molecular imaging. By harnessing the advances in technology, cardiac CT has advanced beyond the mere evaluation of coronary stenosis to an imaging modality tool that permits accurate plaque characterization, assessment of myocardial perfusion and even probing of molecular processes that are involved in coronary atherosclerosis. Novel innovations in CT contrast agents and pre-clinical spectral CT devices have paved the way for CT-based molecular imaging. PMID:26068288

Super-resolution Imaging of Chemical Synapses in the Brain

PubMed Central

Dani, Adish; Huang, Bo; Bergan, Joseph; Dulac, Catherine; Zhuang, Xiaowei

2010-01-01

Determination of the molecular architecture of synapses requires nanoscopic image resolution and specific molecular recognition, a task that has so far defied many conventional imaging approaches. Here we present a super-resolution fluorescence imaging method to visualize the molecular architecture of synapses in the brain. Using multicolor, three-dimensional stochastic optical reconstruction microscopy, the distributions of synaptic proteins can be measured with nanometer precision. Furthermore, the wide-field, volumetric imaging method enables high-throughput, quantitative analysis of a large number of synapses from different brain regions. To demonstrate the capabilities of this approach, we have determined the organization of ten protein components of the presynaptic active zone and the postsynaptic density. Variations in synapse morphology, neurotransmitter receptor composition, and receptor distribution were observed both among synapses and across different brain regions. Combination with optogenetics further allowed molecular events associated with synaptic plasticity to be resolved at the single-synapse level. PMID:21144999

Adipose Tissue Quantification by Imaging Methods: A Proposed Classification

PubMed Central

Shen, Wei; Wang, ZiMian; Punyanita, Mark; Lei, Jianbo; Sinav, Ahmet; Kral, John G.; Imielinska, Celina; Ross, Robert; Heymsfield, Steven B.

2007-01-01

Recent advances in imaging techniques and understanding of differences in the molecular biology of adipose tissue has rendered classical anatomy obsolete, requiring a new classification of the topography of adipose tissue. Adipose tissue is one of the largest body compartments, yet a classification that defines specific adipose tissue depots based on their anatomic location and related functions is lacking. The absence of an accepted taxonomy poses problems for investigators studying adipose tissue topography and its functional correlates. The aim of this review was to critically examine the literature on imaging of whole body and regional adipose tissue and to create the first systematic classification of adipose tissue topography. Adipose tissue terminology was examined in over 100 original publications. Our analysis revealed inconsistencies in the use of specific definitions, especially for the compartment termed “visceral” adipose tissue. This analysis leads us to propose an updated classification of total body and regional adipose tissue, providing a well-defined basis for correlating imaging studies of specific adipose tissue depots with molecular processes. PMID:12529479

Novel molecular imaging ligands targeting matrix metalloproteinases 2 and 9 for imaging of unstable atherosclerotic plaques

PubMed Central

Molenaar, Ger; de Waard, Vivian; Lutgens, Esther; van Eck-Smit, Berthe L. F.; de Bruin, Kora; Piek, Jan J.; Eersels, Jos L. H.; Booij, Jan; Verberne, Hein J.; Windhorst, Albert D.

2017-01-01

Molecular imaging of matrix metalloproteinases (MMPs) may allow detection of atherosclerotic lesions vulnerable to rupture. In this study, we develop a novel radiolabelled compound that can target gelatinase MMP subtypes (MMP2/9) with high selectivity and inhibitory potency. Inhibitory potencies of several halogenated analogues of MMP subtype-selective inhibitors (N-benzenesulfonyliminodiacetyl monohydroxamates and N-halophenoxy-benzenesulfonyl iminodiacetyl monohydroxamates) were in the nanomolar range for MMP2/9. The analogue with highest inhibitory potency and selectivity was radiolabelled with [123I], resulting in moderate radiochemical yield, and high radiochemical purity. Biodistribution studies in mice, revealed stabilization in blood 1 hour after intravenous bolus injection. Intravenous infusion of the radioligand and subsequent autoradiography of excised aortas showed tracer uptake in atheroprone mice. Distribution of the radioligand showed co-localization with MMP2/9 immunohistochemical staining. In conclusion, we have developed a novel selective radiolabeled MMP2/9 inhibitor, suitable for single photon emission computed tomography (SPECT) imaging that effectively targets atherosclerotic lesions in mice. PMID:29190653

Preanalytical considerations in detection of colorectal cancer in blood serum using Raman molecular imaging (Conference Presentation)

NASA Astrophysics Data System (ADS)

Treado, Patrick J.; Stewart, Shona D.; Smith, Aaron; Kirschner, Heather; Post, Christopher; Overholt, Bergein F.

2016-03-01

Colorectal cancer (CRC) is the third most common cancer in men and women in the United States. Raman Molecular Imaging (RMI) is an effective technique to evaluate human tissue, cells and bodily fluids, including blood serum for disease diagnosis. ChemImage Corporation, in collaboration with clinicians, has been engaged in development of an in vitro diagnostic Raman assay focused on CRC detection. The Raman Assay for Colorectal Cancer (RACC) exploits the high specificity of Raman imaging to distinguish diseased from normal dried blood serum droplets without additional reagents. Pilot Study results from testing of hundreds of biobank patient samples have demonstrated that RACC detects CRC with high sensitivity and specificity. However, expanded clinical trials, which are ongoing, are revealing a host of important preanalytical considerations associated with sample collection, sample storage and stability, sample shipping, sample preparation and sample interferents, which impact detection performance. Results from recent clinical studies will be presented.

Imaging enabled platforms for development of therapeutics

NASA Astrophysics Data System (ADS)

Celli, Jonathan; Rizvi, Imran; Blanden, Adam R.; Evans, Conor L.; Abu-Yousif, Adnan O.; Spring, Bryan Q.; Muzikansky, Alona; Pogue, Brian W.; Finkelstein, Dianne M.; Hasan, Tayyaba

2011-03-01

Advances in imaging and spectroscopic technologies have enabled the optimization of many therapeutic modalities in cancer and noncancer pathologies either by earlier disease detection or by allowing therapy monitoring. Amongst the therapeutic options benefiting from developments in imaging technologies, photodynamic therapy (PDT) is exceptional. PDT is a photochemistry-based therapeutic approach where a light-sensitive molecule (photosensitizer) is activated with light of appropriate energy (wavelength) to produce reactive molecular species such as free radicals and singlet oxygen. These molecular entities then react with biological targets such as DNA, membranes and other cellular components to impair their function and lead to eventual cell and tissue death. Development of PDT-based imaging also provides a platform for rapid screening of new therapeutics in novel in vitro models prior to expensive and labor-intensive animal studies. In this study we demonstrate how an imaging platform can be used for strategizing a novel combination treatment strategy for multifocal ovarian cancer. Using an in vitro 3D model for micrometastatic ovarian cancer in conjunction with quantitative imaging we examine dose and scheduling strategies for PDT in combination with carboplatin, a chemotherapeutic agent presently in clinical use for management of this deadly form of cancer.

Cysteamine-based cell-permeable Zn(2+)-specific molecular bioimaging materials: from animal to plant cells.

PubMed

Sinha, Sougata; Dey, Gourab; Kumar, Sunil; Mathew, Jomon; Mukherjee, Trinetra; Mukherjee, Subhrakanti; Ghosh, Subrata

2013-11-27

Structure-interaction/fluorescence relationship studies led to the development of a small chemical library of Zn(2+)-specific cysteamine-based molecular probes. The probe L5 with higher excitation/emission wavelengths, which absorbs in the visible region and emits in the green, was chosen as a model imaging material for biological studies. After successful imaging of intracellular zinc in four different kinds of cells including living organisms, plant, and animal cells, in vivo imaging potential of L5 was evaluated using plant systems. In vivo imaging of translocation of zinc through the stem of a small herb with a transparent stem, Peperomia pellucida, confirmed the stability of L5 inside biological systems and the suitability of L5 for real-time analysis. Similarly, fluorescence imaging of zinc in gram sprouts revealed the efficacy of the probe in the detection and localization of zinc in cereal crops. This imaging technique will help in knowing the efficiency of various techniques used for zinc enrichment of cereal crops. Computational analyses were carried out to better understand the structure, the formation of probe-Zn(2+) complexes, and the emission properties of these complexes.

Imaging of pharmacokinetic rates of indocyanine green in mouse liver with a hybrid fluorescence molecular tomography/x-ray computed tomography system.

PubMed

Zhang, Guanglei; Liu, Fei; Zhang, Bin; He, Yun; Luo, Jianwen; Bai, Jing

2013-04-01

Pharmacokinetic rates have the potential to provide quantitative physiological and pathological information for biological studies and drug development. Fluorescence molecular tomography (FMT) is an attractive imaging tool for three-dimensionally resolving fluorophore distribution in small animals. In this letter, pharmacokinetic rates of indocyanine green (ICG) in mouse liver are imaged with a hybrid FMT and x-ray computed tomography (XCT) system. A recently developed FMT method using structural priors from an XCT system is adopted to improve the quality of FMT reconstruction. In the in vivo experiments, images of uptake and excretion rates of ICG in mouse liver are obtained, which can be used to quantitatively evaluate liver function. The accuracy of the results is validated by a fiber-based fluorescence measurement system.

Live Imaging of Centriole Dynamics by Fluorescently Tagged Proteins in Starfish Oocyte Meiosis.

PubMed

Borrego-Pinto, Joana; Somogyi, Kálmán; Lénárt, Péter

2016-01-01

High throughput DNA sequencing, the decreasing costs of DNA synthesis, and universal techniques for genetic manipulation have made it much easier and quicker to establish molecular tools for any organism than it has been 5 years ago. This opens a great opportunity for reviving "nonconventional" model organisms, which are particularly suited to study a specific biological process and many of which have already been established before the era of molecular biology. By taking advantage of transcriptomics, in particular, these systems can now be easily turned into full fetched models for molecular cell biology.As an example, here we describe how we established molecular tools in the starfish Patiria miniata, which has been a popular model for cell and developmental biology due to the synchronous and rapid development, transparency, and easy handling of oocytes, eggs, and embryos. Here, we detail how we used a de novo assembled transcriptome to produce molecular markers and established conditions for live imaging to investigate the molecular mechanisms underlying centriole elimination-a poorly understood process essential for sexual reproduction of animal species.

Visualizing tissue molecular structure of a black type of canola (Brassica) seed with a thick seed coat after heat-related processing in a chemical way.

PubMed

Yu, Peiqiang

2013-02-20

Heat-related processing of cereal grains, legume seeds, and oil seeds could be used to improve nutrient availability in ruminants. However, different types of processing may have a different impact on intrinsic structure of tissues. To date, there is little research on structure changes after processing within intact tissues. The synchrotron-based molecular imaging technique enables us to detect inherent structure change on a molecular level. The objective of this study was to visualize tissue of black-type canola (Brassica) seed with a thick seed coat after heat-related processing in a chemical way using the synchrotron imaging technique. The results showed that the chemical images of protein amides were obtained through the imaging technique for the raw, wet, and dry heated black type of canola seed tissues. It seems that different types of processing have a different impact on the protein spectral profile in the black type of canola tissues. Wet heating had a greater impact on the protein α-helix to β-sheet ratio than dry heating. Both dry and wet heating resulted in different patterns in amide I, the second derivative, and FSD spectra. However, the exact differences in the tissue images are relatively difficult to be obtained through visual comparison. Future studies should focus on (1) comparing the response and sensitivity of canola seeds to various processing methods between the yellow-type and black-type of canola seeds; (2) developing a sensitive method to compare the image difference between tissues and between treatments; (3) developing a method to link images to nutrient digestion, and (4) revealing how structure changes affect nutrient absorption in humans and animals.

Sentinel lymph node detection in breast cancer patients using surgical navigation system based on fluorescence molecular imaging technology

NASA Astrophysics Data System (ADS)

Chi, Chongwei; Kou, Deqiang; Ye, Jinzuo; Mao, Yamin; Qiu, Jingdan; Wang, Jiandong; Yang, Xin; Tian, Jie

2015-03-01

Introduction: Precision and personalization treatments are expected to be effective methods for early stage cancer studies. Breast cancer is a major threat to women's health and sentinel lymph node biopsy (SLNB) is an effective method to realize precision and personalized treatment for axillary lymph node (ALN) negative patients. In this study, we developed a surgical navigation system (SNS) based on optical molecular imaging technology for the precise detection of the sentinel lymph node (SLN) in breast cancer patients. This approach helps surgeons in precise positioning during surgery. Methods: The SNS was mainly based on the technology of optical molecular imaging. A novel optical path has been designed in our hardware system and a feature-matching algorithm has been devised to achieve rapid fluorescence and color image registration fusion. Ten in vivo studies of SLN detection in rabbits using indocyanine green (ICG) and blue dye were executed for system evaluation and 8 breast cancer patients accepted the combination method for therapy. Results: The detection rate of the combination method was 100% and an average of 2.6 SLNs was found in all patients. Our results showed that the method of using SNS to detect SLN has the potential to promote its application. Conclusion: The advantage of this system is the real-time tracing of lymph flow in a one-step procedure. The results demonstrated the feasibility of the system for providing accurate location and reliable treatment for surgeons. Our approach delivers valuable information and facilitates more detailed exploration for image-guided surgery research.

Validation of nonlinear interferometric vibrational imaging as a molecular OCT technique by the use of Raman microscopy

NASA Astrophysics Data System (ADS)

Benalcazar, Wladimir A.; Jiang, Zhi; Marks, Daniel L.; Geddes, Joseph B.; Boppart, Stephen A.

2009-02-01

We validate a molecular imaging technique called Nonlinear Interferometric Vibrational Imaging (NIVI) by comparing vibrational spectra with those acquired from Raman microscopy. This broadband coherent anti-Stokes Raman scattering (CARS) technique uses heterodyne detection and OCT acquisition and design principles to interfere a CARS signal generated by a sample with a local oscillator signal generated separately by a four-wave mixing process. These are mixed and demodulated by spectral interferometry. Its confocal configuration allows the acquisition of 3D images based on endogenous molecular signatures. Images from both phantom and mammary tissues have been acquired by this instrument and its spectrum is compared with its spontaneous Raman signatures.

The Basic Principles of FDG-PET/CT Imaging.

PubMed

Basu, Sandip; Hess, Søren; Nielsen Braad, Poul-Erik; Olsen, Birgitte Brinkmann; Inglev, Signe; Høilund-Carlsen, Poul Flemming

2014-10-01

Positron emission tomography (PET) imaging with 2-[(18)F]fluoro-2-deoxy-D-glucose (FDG) forms the basis of molecular imaging. FDG-PET imaging is a multidisciplinary undertaking that requires close interdisciplinary collaboration in a broad team comprising physicians, technologists, secretaries, radio-chemists, hospital physicists, molecular biologists, engineers, and cyclotron technicians. The aim of this review is to provide a brief overview of important basic issues and considerations pivotal to successful patient examinations, including basic physics, instrumentation, radiochemistry, molecular and cell biology, patient preparation, normal distribution of tracer, and potential interpretive pitfalls. Copyright © 2014 Elsevier Inc. All rights reserved.

Experiment-scale molecular simulation study of liquid crystal thin films

NASA Astrophysics Data System (ADS)

Nguyen, Trung Dac; Carrillo, Jan-Michael Y.; Matheson, Michael A.; Brown, W. Michael

2014-03-01

Supercomputers have now reached a performance level adequate for studying thin films with molecular detail at the relevant scales. By exploiting the power of GPU accelerators on Titan, we have been able to perform simulations of characteristic liquid crystal films that provide remarkable qualitative agreement with experimental images. We have demonstrated that key features of spinodal instability can only be observed with sufficiently large system sizes, which were not accessible with previous simulation studies. Our study emphasizes the capability and significance of petascale simulations in providing molecular-level insights in thin film systems as well as other interfacial phenomena.

Next generation of optical diagnostics for bladder cancer using probe-based confocal laser endomicroscopy

NASA Astrophysics Data System (ADS)

Liu, Jen-Jane; Chang, Timothy C.; Pan, Ying; Hsiao, Shelly T.; Mach, Kathleen E.; Jensen, Kristin C.; Liao, Joseph C.

2012-02-01

Real-time imaging with confocal laser endomicroscopy (CLE) probes that fit in standard endoscopes has emerged as a clinically feasible technology for optical biopsy of bladder cancer. Confocal images of normal, inflammatory, and neoplastic urothelium obtained with intravesical fluorescein can be differentiated by morphologic characteristics. We compiled a confocal atlas of the urinary tract using these diagnostic criteria to be used in a prospective diagnostic accuracy study. Patients scheduled to undergo transurethral resection of bladder tumor underwent white light cystoscopy (WLC), followed by CLE, and histologic confirmation of resected tissue. Areas that appeared normal by WLC were imaged and biopsied as controls. We imaged and prospectively analyzed 135 areas in 57 patients. We show that CLE improves the diagnostic accuracy of WLC for diagnosing benign tissue, low and high grade cancer. Interobserver studies showed a moderate level of agreement by urologists and nonclinical researchers. Despite morphologic differences between inflammation and cancer, real-time differentiation can still be challenging. Identification of bladder cancer-specific contrast agents could provide molecular specificity to CLE. By using fluorescently-labeled antibodies or peptides that bind to proteins expressed in bladder cancer, we have identified putative molecular contrast agents for targeted imaging with CLE. We describe one candidate agent - anti-CD47 - that was instilled into bladder specimens. The tumor and normal urothelium were imaged with CLE, with increased fluorescent signal demonstrated in areas of tumor compared to normal areas. Thus, cancer-specificity can be achieved using molecular contrast agents ex vivo in conjunction with CLE.

Cavity-enhanced Raman microscopy of individual carbon nanotubes

PubMed Central

Hümmer, Thomas; Noe, Jonathan; Hofmann, Matthias S.; Hänsch, Theodor W.; Högele, Alexander; Hunger, David

2016-01-01

Raman spectroscopy reveals chemically specific information and provides label-free insight into the molecular world. However, the signals are intrinsically weak and call for enhancement techniques. Here, we demonstrate Purcell enhancement of Raman scattering in a tunable high-finesse microcavity, and utilize it for molecular diagnostics by combined Raman and absorption imaging. Studying individual single-wall carbon nanotubes, we identify crucial structural parameters such as nanotube radius, electronic structure and extinction cross-section. We observe a 320-times enhanced Raman scattering spectral density and an effective Purcell factor of 6.2, together with a collection efficiency of 60%. Potential for significantly higher enhancement, quantitative signals, inherent spectral filtering and absence of intrinsic background in cavity-vacuum stimulated Raman scattering render the technique a promising tool for molecular imaging. Furthermore, cavity-enhanced Raman transitions involving localized excitons could potentially be used for gaining quantum control over nanomechanical motion and open a route for molecular cavity optomechanics. PMID:27402165

Molecular classification of patients with grade II/III glioma using quantitative MRI characteristics.

PubMed

Bahrami, Naeim; Hartman, Stephen J; Chang, Yu-Hsuan; Delfanti, Rachel; White, Nathan S; Karunamuni, Roshan; Seibert, Tyler M; Dale, Anders M; Hattangadi-Gluth, Jona A; Piccioni, David; Farid, Nikdokht; McDonald, Carrie R

2018-06-02

Molecular markers of WHO grade II/III glioma are known to have important prognostic and predictive implications and may be associated with unique imaging phenotypes. The purpose of this study is to determine whether three clinically relevant molecular markers identified in gliomas-IDH, 1p/19q, and MGMT status-show distinct quantitative MRI characteristics on FLAIR imaging. Sixty-one patients with grade II/III gliomas who had molecular data and MRI available prior to radiation were included. Quantitative MRI features were extracted that measured tissue heterogeneity (homogeneity and pixel correlation) and FLAIR border distinctiveness (edge contrast; EC). T-tests were conducted to determine whether patients with different genotypes differ across the features. Logistic regression with LASSO regularization was used to determine the optimal combination of MRI and clinical features for predicting molecular subtypes. Patients with IDH wildtype tumors showed greater signal heterogeneity (p = 0.001) and lower EC (p = 0.008) within the FLAIR region compared to IDH mutant tumors. Among patients with IDH mutant tumors, 1p/19q co-deleted tumors had greater signal heterogeneity (p = 0.002) and lower EC (p = 0.005) compared to 1p/19q intact tumors. MGMT methylated tumors showed lower EC (p = 0.03) compared to the unmethylated group. The combination of FLAIR border distinctness, heterogeneity, and pixel correlation optimally classified tumors by IDH status. Quantitative imaging characteristics of FLAIR heterogeneity and border pattern in grade II/III gliomas may provide unique information for determining molecular status at time of initial diagnostic imaging, which may then guide subsequent surgical and medical management.

Targeting PSMA by radioligands in non-prostate disease-current status and future perspectives.

PubMed

Backhaus, Philipp; Noto, Benjamin; Avramovic, Nemanja; Grubert, Lena Sophie; Huss, Sebastian; Bögemann, Martin; Stegger, Lars; Weckesser, Matthias; Schäfers, Michael; Rahbar, Kambiz

2018-05-01

Prostate-specific membrane antigen (PSMA) is the up-and-coming target for molecular imaging of prostate cancer. Despite its name, non-prostate-related PSMA expression in physiologic tissue as well as in benign and malignant disease has been reported in various publications. Unlike in prostate cancer, PSMA expression is only rarely observed in non-prostate tumor cells. Instead, expression occurs in endothelial cells of tumor-associated neovasculature, although no endothelial expression is observed under physiologic conditions. The resulting potential for tumor staging in non-prostate malignant tumors has been demonstrated in first patient studies. This review summarizes the first clinical studies and deduces future perspectives in staging, molecular characterization, and PSMA-targeted radionuclide therapy based on histopathologic examinations of PSMA expression. The non-exclusivity of PSMA in prostate cancer opens a window to utilize the spectrum of available radioactive PSMA ligands for imaging and molecular characterization and maybe even therapy of non-prostate disease.

Super-resolution and super-localization microscopy: A novel tool for imaging chemical and biological processes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dong, Bin

2015-01-01

Optical microscopy imaging of single molecules and single particles is an essential method for studying fundamental biological and chemical processes at the molecular and nanometer scale. The best spatial resolution (~ λ/2) achievable in traditional optical microscopy is governed by the diffraction of light. However, single molecule-based super-localization and super-resolution microscopy imaging techniques have emerged in the past decade. Individual molecules can be localized with nanometer scale accuracy and precision for studying of biological and chemical processes.This work uncovered the heterogeneous properties of the pore structures. In this dissertation, the coupling of molecular transport and catalytic reaction at the singlemore » molecule and single particle level in multilayer mesoporous nanocatalysts was elucidated. Most previous studies dealt with these two important phenomena separately. A fluorogenic oxidation reaction of non-fluorescent amplex red to highly fluorescent resorufin was tested. The diffusion behavior of single resorufin molecules in aligned nanopores was studied using total internal reflection fluorescence microscopy (TIRFM).« less

Clinical perspectives of hybrid proton-fluorine magnetic resonance imaging and spectroscopy.

PubMed

Wolters, Martijn; Mohades, Seyede G; Hackeng, Tilman M; Post, Mark J; Kooi, Marianne E; Backes, Walter H

2013-05-01

The number of applications of fluorine 19 (19F) magnetic resonance (MR) imaging and spectroscopy in biomedical and clinical research is steadily growing. The 100% natural abundance of fluorine and its relatively high sensitivity for MR (83% to that of protons) make it an interesting nucleus for a wide range of MR applications. Fluorinated contrast media have a number of advantages over the conventionally used gadolinium-based or iron-based contrast agents. The absence of an endogenous fluorine background intensity in the human body facilitates reliable quantification of fluorinated contrast medium or drugs. Anatomy can be visualized separately with proton MR imaging, creating the application of hybrid hydrogen 1 (1H)/19F MR imaging. The availability of 2 channels (ie, the 1H and 19F channels) enables dual-targeted molecular imaging. Recently, novel developments have emerged on fluorine-based contrast media in preclinical studies and imaging techniques. The developments in fluorine MR seem promising for clinical applications, with contributions in therapy monitoring, assessment of lung function, angiography, and molecular imaging. This review outlines the translation from recent advances in preclinical MR imaging and spectroscopy to future perspectives of clinical hybrid 1H/19/F MR imaging applications.

Quantitative diffusion weighted imaging parameters in tumor and peritumoral stroma for prediction of molecular subtypes in breast cancer

NASA Astrophysics Data System (ADS)

He, Ting; Fan, Ming; Zhang, Peng; Li, Hui; Zhang, Juan; Shao, Guoliang; Li, Lihua

2018-03-01

Breast cancer can be classified into four molecular subtypes of Luminal A, Luminal B, HER2 and Basal-like, which have significant differences in treatment and survival outcomes. We in this study aim to predict immunohistochemistry (IHC) determined molecular subtypes of breast cancer using image features derived from tumor and peritumoral stroma region based on diffusion weighted imaging (DWI). A dataset of 126 breast cancer patients were collected who underwent preoperative breast MRI with a 3T scanner. The apparent diffusion coefficients (ADCs) were recorded from DWI, and breast image was segmented into regions comprising the tumor and the surrounding stromal. Statistical characteristics in various breast tumor and peritumoral regions were computed, including mean, minimum, maximum, variance, interquartile range, range, skewness, and kurtosis of ADC values. Additionally, the difference of features between each two regions were also calculated. The univariate logistic based classifier was performed for evaluating the performance of the individual features for discriminating subtypes. For multi-class classification, multivariate logistic regression model was trained and validated. The results showed that the tumor boundary and proximal peritumoral stroma region derived features have a higher performance in classification compared to that of the other regions. Furthermore, the prediction model using statistical features, difference features and all the features combined from these regions generated AUC values of 0.774, 0.796 and 0.811, respectively. The results in this study indicate that ADC feature in tumor and peritumoral stromal region would be valuable for estimating the molecular subtype in breast cancer.

Molecular Imaging and Radionuclide Therapy of Melanoma Targeting the Melanocortin 1 Receptor

PubMed Central

Zhang, Chengcheng; Lin, Kuo-Shyan; Bénard, François

2017-01-01

Melanoma is a deadly disease at late metastatic stage, and early diagnosis and accurate staging remain the key aspects for managing melanoma. The melanocortin 1 receptor (MC1 R) is overexpressed in primary and metastatic melanomas, and its endogenous ligand, the α-melanocyte-stimulating hormone (αMSH), has been extensively studied for the development of MC1 R-targeted molecular imaging and therapy of melanoma. Natural αMSH is not well suited for this purpose due to low stability in vivo. Unnatural amino acid substitutions substantially stabilized the peptide, while cyclization via lactam bridge and metal coordination further improved binding affinity and stability. In this study, we summarized the development and the in vitro and in vivo characteristics of the radiolabeled αMSH analogues, including 99mTc-, 111In-, 67 Ga-, or 125I-labeled αMSH analogues for imaging with single-photon emission computed tomography; 68Ga-, 64Cu-, or 18F-labeled αMSH analogues for imaging with positron emission tomography; and 188Re-, 177Lu-, 90Y-, or 212Pb-labeled αMSH analogues for radionuclide therapy. These radiolabeled αMSH analogues showed promising results with high tumor uptake and rapid normal tissue activity clearance in the preclinical model of B16F1 and B16F10 mouse melanomas. These results highlight the potential of using radiolabeled αMSH analogues in clinical applications for molecular imaging and radionuclide therapy of melanoma. PMID:29182034

In Vivo Demonstration of Cancer Molecular Imaging with Ultrasound Radiation Force and Buried-Ligand Microbubbles

PubMed Central

Borden, Mark A.; Streeter, Jason E.; Sirsi, Shashank R.; Dayton, Paul A.

2015-01-01

In designing targeted contrast agent materials for imaging, the need to present a targeting ligand for recognition and binding by the target is counterbalanced by the need to minimize interactions with plasma components and to avoid recognition by the immune system. We have previously reported on a microbubble imaging probe for ultrasound molecular imaging that uses a buried-ligand surface architecture to minimize unwanted interactions and immunogenicity. Here we examine for the first time the utility of this approach for in vivo molecular imaging. In accordance with previous results, we showed a threefold increase in circulation persistence through the tumor of a fibrosarcoma model in comparison with controls. The buried-ligand microbubbles were then activated for targeted adhesion through the application of noninvasive ultrasound radiation forces applied specifically to the tumor region. Using a clinical ultrasound scanner, microbubbles were activated, imaged, and silenced. The results showed visually conspicuous images of tumor neovasculature and a twofold increase in ultrasound radiation force enhancement of acoustic contrast intensity for buried-ligand microbubbles, whereas no such increase was found for exposed-ligand microbubbles. We therefore conclude that the use of acoustically active buried-ligand microbubbles for ultrasound molecular imaging bridges the demand for low immunogenicity with the necessity of maintaining targeting efficacy and imaging conspicuity in vivo. PMID:23981781

Molecular Imaging of Hydrolytic Enzymes Using PET and SPECT

PubMed Central

Rempel, Brian P.; Price, Eric W.

2017-01-01

Hydrolytic enzymes are a large class of biological catalysts that play a vital role in a plethora of critical biochemical processes required to maintain human health. However, the expression and/or activity of these important enzymes can change in many different diseases and therefore represent exciting targets for the development of positron emission tomography (PET) and single-photon emission computed tomography (SPECT) radiotracers. This review focuses on recently reported radiolabeled substrates, reversible inhibitors, and irreversible inhibitors investigated as PET and SPECT tracers for imaging hydrolytic enzymes. By learning from the most successful examples of tracer development for hydrolytic enzymes, it appears that an early focus on careful enzyme kinetics and cell-based studies are key factors for identifying potentially useful new molecular imaging agents. PMID:28927325

Molecular Imaging of Hydrolytic Enzymes Using PET and SPECT.

PubMed

Rempel, Brian P; Price, Eric W; Phenix, Christopher P

2017-01-01

Hydrolytic enzymes are a large class of biological catalysts that play a vital role in a plethora of critical biochemical processes required to maintain human health. However, the expression and/or activity of these important enzymes can change in many different diseases and therefore represent exciting targets for the development of positron emission tomography (PET) and single-photon emission computed tomography (SPECT) radiotracers. This review focuses on recently reported radiolabeled substrates, reversible inhibitors, and irreversible inhibitors investigated as PET and SPECT tracers for imaging hydrolytic enzymes. By learning from the most successful examples of tracer development for hydrolytic enzymes, it appears that an early focus on careful enzyme kinetics and cell-based studies are key factors for identifying potentially useful new molecular imaging agents.

ATOMIC RESOLUTION CRYO ELECTRON MICROSCOPY OF MACROMOLECULAR COMPLEXES

PubMed Central

ZHOU, Z. HONG

2013-01-01

Single-particle cryo electron microscopy (cryoEM) is a technique for determining three-dimensional (3D) structures from projection images of molecular complexes preserved in their “native,” noncrystalline state. Recently, atomic or near-atomic resolution structures of several viruses and protein assemblies have been determined by single-particle cryoEM, allowing ab initio atomic model building by following the amino acid side chains or nucleic acid bases identifiable in their cryoEM density maps. In particular, these cryoEM structures have revealed extended arms contributing to molecular interactions that are otherwise not resolved by the conventional structural method of X-ray crystallography at similar resolutions. High-resolution cryoEM requires careful consideration of a number of factors, including proper sample preparation to ensure structural homogeneity, optimal configuration of electron imaging conditions to record high-resolution cryoEM images, accurate determination of image parameters to correct image distortions, efficient refinement and computation to reconstruct a 3D density map, and finally appropriate choice of modeling tools to construct atomic models for functional interpretation. This progress illustrates the power of cryoEM and ushers it into the arsenal of structural biology, alongside conventional techniques of X-ray crystallography and NMR, as a major tool (and sometimes the preferred one) for the studies of molecular interactions in supramolecular assemblies or machines. PMID:21501817

Dual-isotope Cryo-imaging Quantitative Autoradiography (CIQA): Anvestigating Antibody-Drug Conjugate Distribution And Payload Delivery Through Imaging.

PubMed

Ilovich, Ohad; Qutaish, Mohammed; Hesterman, Jacob; Orcutt, Kelly; Hoppin, Jack; Polyak, Ildiko; Seaman, Marc; Abu-Yousif, Adnan; Cvet, Donna; Bradley, Daniel

2018-05-04

In vitro properties of antibody drug conjugates (ADCs) such as binding, internalization, and cytotoxicity are often well characterized prior to in vivo studies. Interpretation of in vivo studies could significantly be enhanced by molecular imaging tools. We present here a dual-isotope cryo-imaging quantitative autoradiography (CIQA) methodology combined with advanced 3D imaging and analysis allowing for the simultaneous study of both antibody and payload distribution in tissues of interest. in a pre-clinical setting. Methods: TAK-264, an investigational anti-guanylyl cyclase C (GCC) targeting ADC was synthesized utilizing tritiated Monomethyl auristatin E (MMAE). The tritiated ADC was then conjugated to DTPA, labeled with indium-111 and evaluated in vivo in GCC-positive and GCC-negative tumor-bearing animals. Results: Cryo-imaging Quantitative Autoradiography (CIQA) reveals the time course of drug release from ADC and its distribution into various tumor regions seemingly impenetrablethat are less accessible to the antibody. For GCC-positive tumors, a representative section obtained 96 hours post tracer injection showed only 0.8% of the voxels have co-localized signal versus over 15% of the voxels for a GCC-negative tumor section., suggesting successful and specific cleaving of the toxin in the antigen positive lesions. Conclusion: The combination of a veteran established autoradiography technology with advanced image analysis methodologies affords an experimental tool that can support detailed characterization of ADC tumor penetration and pharmacokinetics. Copyright © 2018 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Molecular Imaging and Precision Medicine in Dementia and Movement Disorders.

PubMed

Mallik, Atul K; Drzezga, Alexander; Minoshima, Satoshi

2017-01-01

Precision medicine (PM) has been defined as "prevention and treatment strategies that take individual variability into account." Molecular imaging (MI) is an ideally suited tool for PM approaches to neurodegenerative dementia and movement disorders (MD). Here we review PM approaches and discuss how they may be applied to other associated neurodegenerative dementia and MD. With ongoing major therapeutic research initiatives that include the use of molecular imaging, we look forward to established interventions targeted to specific molecular pathophysiology and expect the potential benefit of MI PM approaches in neurodegenerative dementia and MD will only increase. Copyright © 2016 Elsevier Inc. All rights reserved.

Inflammation Modulates Murine Venous Thrombosis Resolution In Vivo: Assessment by Multimodal Fluorescence Molecular Imaging

PubMed Central

Ripplinger, Crystal M.; Kessinger, Chase W.; Li, Chunqiang; Kim, Jin Won; McCarthy, Jason R.; Weissleder, Ralph; Henke, Peter K.; Lin, Charles P.; Jaffer, Farouc A.

2012-01-01

Objective Assessment of thrombus inflammation in vivo could provide new insights into deep vein thrombosis (DVT) resolution. Here we develop and evaluate two integrated fluorescence molecular-structural imaging strategies to quantify DVT-related inflammation and architecture, and to assess the effect of thrombus inflammation on subsequent DVT resolution in vivo. Methods and Results Murine DVT were created with topical 5% FeCl3 application to thigh or jugular veins (n=35). On day 3, mice received macrophage and matrix metalloproteinase (MMP) activity fluorescence imaging agents. On day 4, integrated assessment of DVT inflammation and architecture was performed using confocal fluorescence intravital microscopy (IVM). Day 4 analyses showed robust relationships among in vivo thrombus macrophages, MMP activity, and FITC-dextran deposition (r>0.70, p<0.01). In a serial two-timepoint study, mice with DVT underwent IVM at day 4 and at day 6. Analyses revealed that the intensity of thrombus inflammation at day 4 predicted the magnitude of DVT resolution at day 6 (p<0.05). In a second approach, noninvasive fluorescence molecular tomography-computed tomography (FMT-CT) was employed, and detected macrophages within jugular DVT (p<0.05 vs. sham-controls). Conclusions Integrated fluorescence molecular-structural imaging demonstrates that the DVT-induced inflammatory response can be readily assessed in vivo, and can inform the magnitude of thrombus resolution. PMID:22995524

Breast Cancer Detection by B7-H3-Targeted Ultrasound Molecular Imaging.

PubMed

Bachawal, Sunitha V; Jensen, Kristin C; Wilson, Katheryne E; Tian, Lu; Lutz, Amelie M; Willmann, Jürgen K

2015-06-15

Ultrasound complements mammography as an imaging modality for breast cancer detection, especially in patients with dense breast tissue, but its utility is limited by low diagnostic accuracy. One emerging molecular tool to address this limitation involves contrast-enhanced ultrasound using microbubbles targeted to molecular signatures on tumor neovasculature. In this study, we illustrate how tumor vascular expression of B7-H3 (CD276), a member of the B7 family of ligands for T-cell coregulatory receptors, can be incorporated into an ultrasound method that can distinguish normal, benign, precursor, and malignant breast pathologies for diagnostic purposes. Through an IHC analysis of 248 human breast specimens, we found that vascular expression of B7-H3 was selectively and significantly higher in breast cancer tissues. B7-H3 immunostaining on blood vessels distinguished benign/precursors from malignant lesions with high diagnostic accuracy in human specimens. In a transgenic mouse model of cancer, the B7-H3-targeted ultrasound imaging signal was increased significantly in breast cancer tissues and highly correlated with ex vivo expression levels of B7-H3 on quantitative immunofluorescence. Our findings offer a preclinical proof of concept for the use of B7-H3-targeted ultrasound molecular imaging as a tool to improve the diagnostic accuracy of breast cancer detection in patients. ©2015 American Association for Cancer Research.

Design and Implementation of a Self-Directed Stereochemistry Lesson Using Embedded Virtual Three-Dimensional Images in a Portable Document Format

ERIC Educational Resources Information Center

Cody, Jeremy A.; Craig, Paul A.; Loudermilk, Adam D.; Yacci, Paul M.; Frisco, Sarah L.; Milillo, Jennifer R.

2012-01-01

A novel stereochemistry lesson was prepared that incorporated both handheld molecular models and embedded virtual three-dimensional (3D) images. The images are fully interactive and eye-catching for the students; methods for preparing 3D molecular images in Adobe Acrobat are included. The lesson was designed and implemented to showcase the 3D…

SLAC All Access: Atomic, Molecular and Optical Science Instrument

ScienceCinema

Bozek, John

2018-02-13

John Bozek, a staff scientist at SLAC's Linac Coherent Light Source (LCLS) X-ray laser who manages the LCLS Soft X-ray Department, takes us behind the scenes at the Atomic, Molecular and Optical Science (AMO) instrument, the first of six experimental stations now operating at LCLS. Samples used in AMO experiments include atoms, molecules, clusters, and nanoscale objects such as protein crystals or viruses. Science performed at AMO includes fundamental studies of light-matter interactions in the extreme X-ray intensity of the LCLS pules, time-resolved studies of increasingly charged states of atoms and molecules, X-ray diffraction imaging of nanocrystals, and single-shot imaging of a variety of objects.

Hyperspectral imaging with laser-scanning sum-frequency generation microscopy

PubMed Central

Hanninen, Adam; Shu, Ming Wai; Potma, Eric O.

2017-01-01

Vibrationally sensitive sum-frequency generation (SFG) microscopy is a chemically selective imaging technique sensitive to non-centrosymmetric molecular arrangements in biological samples. The routine use of SFG microscopy has been hampered by the difficulty of integrating the required mid-infrared excitation light into a conventional, laser-scanning nonlinear optical (NLO) microscope. In this work, we describe minor modifications to a regular laser-scanning microscope to accommodate SFG microscopy as an imaging modality. We achieve vibrationally sensitive SFG imaging of biological samples with sub-μm resolution at image acquisition rates of 1 frame/s, almost two orders of magnitude faster than attained with previous point-scanning SFG microscopes. Using the fast scanning capability, we demonstrate hyperspectral SFG imaging in the CH-stretching vibrational range and point out its use in the study of molecular orientation and arrangement in biologically relevant samples. We also show multimodal imaging by combining SFG microscopy with second-harmonic generation (SHG) and coherent anti-Stokes Raman scattering (CARS) on the same imaging platfrom. This development underlines that SFG microscopy is a unique modality with a spatial resolution and image acquisition time comparable to that of other NLO imaging techniques, making point-scanning SFG microscopy a valuable member of the NLO imaging family. PMID:28966861

Fluorescence circadian imaging reveals a PDF-dependent transcriptional regulation of the Drosophila molecular clock.

PubMed

Sabado, Virginie; Vienne, Ludovic; Nunes, José Manuel; Rosbash, Michael; Nagoshi, Emi

2017-01-30

Circadian locomotor behaviour is controlled by a pacemaker circuit composed of clock-containing neurons. To interrogate the mechanistic relationship between the molecular clockwork and network communication critical to the operation of the Drosophila circadian pacemaker circuit, we established new fluorescent circadian reporters that permit single-cell recording of transcriptional and post-transcriptional rhythms in brain explants and cultured neurons. Live-imaging experiments combined with pharmacological and genetic manipulations demonstrate that the neuropeptide pigment-dispersing factor (PDF) amplifies the molecular rhythms via time-of-day- and activity-dependent upregulation of transcription from E-box-containing clock gene promoters within key pacemaker neurons. The effect of PDF on clock gene transcription and the known role of PDF in enhancing PER/TIM stability occur via independent pathways downstream of the PDF receptor, the former through a cAMP-independent mechanism and the latter through a cAMP-PKA dependent mechanism. These results confirm and extend the mechanistic understanding of the role of PDF in controlling the synchrony of the pacemaker neurons. More broadly, our results establish the utility of the new live-imaging tools for the study of molecular-neural interactions important for the operation of the circadian pacemaker circuit.

Fluorescence circadian imaging reveals a PDF-dependent transcriptional regulation of the Drosophila molecular clock

PubMed Central

Sabado, Virginie; Vienne, Ludovic; Nunes, José Manuel; Rosbash, Michael; Nagoshi, Emi

2017-01-01

Circadian locomotor behaviour is controlled by a pacemaker circuit composed of clock-containing neurons. To interrogate the mechanistic relationship between the molecular clockwork and network communication critical to the operation of the Drosophila circadian pacemaker circuit, we established new fluorescent circadian reporters that permit single-cell recording of transcriptional and post-transcriptional rhythms in brain explants and cultured neurons. Live-imaging experiments combined with pharmacological and genetic manipulations demonstrate that the neuropeptide pigment-dispersing factor (PDF) amplifies the molecular rhythms via time-of-day- and activity-dependent upregulation of transcription from E-box-containing clock gene promoters within key pacemaker neurons. The effect of PDF on clock gene transcription and the known role of PDF in enhancing PER/TIM stability occur via independent pathways downstream of the PDF receptor, the former through a cAMP-independent mechanism and the latter through a cAMP-PKA dependent mechanism. These results confirm and extend the mechanistic understanding of the role of PDF in controlling the synchrony of the pacemaker neurons. More broadly, our results establish the utility of the new live-imaging tools for the study of molecular-neural interactions important for the operation of the circadian pacemaker circuit. PMID:28134281

A targeted nanoglobular contrast agent from host-guest self-assembly for MR cancer molecular imaging.

PubMed

Zhou, Zhuxian; Han, Zhen; Lu, Zheng-Rong

2016-04-01

The clinical application of nanoparticular Gd(III) based contrast agents for tumor molecular MRI has been hindered by safety concerns associated with prolonged tissue retention, although they can produce strong tumor enhancement. In this study, a targeted well-defined cyclodextrin-based nanoglobular contrast agent was developed through self-assembly driven by host-guest interactions for safe and effective cancer molecular MRI. Multiple β-cyclodextrins attached POSS (polyhedral oligomeric silsesquioxane) nanoglobule was used as host molecule. Adamantane-modified macrocyclic Gd(III) contrast agent, cRGD (cyclic RGDfK peptide) targeting ligand and fluorescent probe was used as guest molecules. The targeted host-guest nanoglobular contrast agent cRGD-POSS-βCD-(DOTA-Gd) specifically bond to αvβ3 integrin in malignant 4T1 breast tumor and provided greater contrast enhancement than the corresponding non-targeted agent. The agent also provided significant fluorescence signal in tumor tissue. The histological analysis of the tumor tissue confirmed its specific and effective targeting to αvβ3 integrin. The targeted imaging agent has a potential for specific cancer molecular MR and fluorescent imaging. Copyright © 2016 Elsevier Ltd. All rights reserved.

Integrin Targeted MR Imaging

PubMed Central

Tan, Mingqian; Lu, Zheng-Rong

2011-01-01

Magnetic resonance imaging (MRI) is a powerful medical diagnostic imaging modality for integrin targeted imaging, which uses the magnetic resonance of tissue water protons to display tissue anatomic structures with high spatial resolution. Contrast agents are often used in MRI to highlight specific regions of the body and make them easier to visualize. There are four main classes of MRI contrast agents based on their different contrast mechanisms, including T1, T2, chemical exchange saturation transfer (CEST) agents, and heteronuclear contrast agents. Integrins are an important family of heterodimeric transmembrane glycoproteins that function as mediators of cell-cell and cell-extracellular matrix interactions. The overexpressed integrins can be used as the molecular targets for designing suitable integrin targeted contrast agents for MR molecular imaging. Integrin targeted contrast agent includes a targeting agent specific to a target integrin, a paramagnetic agent and a linker connecting the targeting agent with the paramagnetic agent. Proper selection of targeting agents is critical for targeted MRI contrast agents to effectively bind to integrins for in vivo imaging. An ideal integrin targeted MR contrast agent should be non-toxic, provide strong contrast enhancement at the target sites and can be completely excreted from the body after MR imaging. An overview of integrin targeted MR contrast agents based on small molecular and macromolecular Gd(III) complexes, lipid nanoparticles and superparamagnetic nanoparticles is provided for MR molecular imaging. By using proper delivery systems for loading sufficient Gd(III) chelates or superparamagnetic nanoparticles, effective molecular imaging of integrins with MRI has been demonstrated in animal models. PMID:21547154

Grading of Gliomas by Using Monoexponential, Biexponential, and Stretched Exponential Diffusion-weighted MR Imaging and Diffusion Kurtosis MR Imaging

PubMed Central

Bai, Yan; Lin, Yusong; Tian, Jie; Shi, Dapeng; Cheng, Jingliang; Haacke, E. Mark; Hong, Xiaohua; Ma, Bo; Zhou, Jinyuan

2016-01-01

Purpose To quantitatively compare the potential of various diffusion parameters obtained from monoexponential, biexponential, and stretched exponential diffusion-weighted imaging models and diffusion kurtosis imaging in the grading of gliomas. Materials and Methods This study was approved by the local ethics committee, and written informed consent was obtained from all subjects. Both diffusion-weighted imaging and diffusion kurtosis imaging were performed in 69 patients with pathologically proven gliomas by using a 3-T magnetic resonance (MR) imaging unit. An isotropic apparent diffusion coefficient (ADC), true ADC, pseudo-ADC, and perfusion fraction were calculated from diffusion-weighted images by using a biexponential model. A water molecular diffusion heterogeneity index and distributed diffusion coefficient were calculated from diffusion-weighted images by using a stretched exponential model. Mean diffusivity, fractional anisotropy, and mean kurtosis were calculated from diffusion kurtosis images. All values were compared between high-grade and low-grade gliomas by using a Mann-Whitney U test. Receiver operating characteristic and Spearman rank correlation analysis were used for statistical evaluations. Results ADC, true ADC, perfusion fraction, water molecular diffusion heterogeneity index, distributed diffusion coefficient, and mean diffusivity values were significantly lower in high-grade gliomas than in low-grade gliomas (U = 109, 56, 129, 6, 206, and 229, respectively; P < .05). Pseudo-ADC and mean kurtosis values were significantly higher in high-grade gliomas than in low-grade gliomas (U = 98 and 8, respectively; P < .05). Both water molecular diffusion heterogeneity index (area under the receiver operating characteristic curve [AUC] = 0.993) and mean kurtosis (AUC = 0.991) had significantly greater AUC values than ADC (AUC = 0.866), mean diffusivity (AUC = 0.722), and fractional anisotropy (AUC = 0.500) in the differentiation of low-grade and high-grade gliomas (P < .05). Conclusion Water molecular diffusion heterogeneity index and mean kurtosis values may provide additional information and improve the grading of gliomas compared with conventional diffusion parameters. © RSNA, 2015 Online supplemental material is available for this article. PMID:26230975

Nanoparticle imaging probes for molecular imaging with computed tomography and application to cancer imaging

NASA Astrophysics Data System (ADS)

Roeder, Ryan K.; Curtis, Tyler E.; Nallathamby, Prakash D.; Irimata, Lisa E.; McGinnity, Tracie L.; Cole, Lisa E.; Vargo-Gogola, Tracy; Cowden Dahl, Karen D.

2017-03-01

Precision imaging is needed to realize precision medicine in cancer detection and treatment. Molecular imaging offers the ability to target and identify tumors, associated abnormalities, and specific cell populations with overexpressed receptors. Nuclear imaging and radionuclide probes provide high sensitivity but subject the patient to a high radiation dose and provide limited spatiotemporal information, requiring combined computed tomography (CT) for anatomic imaging. Therefore, nanoparticle contrast agents have been designed to enable molecular imaging and improve detection in CT alone. Core-shell nanoparticles provide a powerful platform for designing tailored imaging probes. The composition of the core is chosen for enabling strong X-ray contrast, multi-agent imaging with photon-counting spectral CT, and multimodal imaging. A silica shell is used for protective, biocompatible encapsulation of the core composition, volume-loading fluorophores or radionuclides for multimodal imaging, and facile surface functionalization with antibodies or small molecules for targeted delivery. Multi-agent (k-edge) imaging and quantitative molecular imaging with spectral CT was demonstrated using current clinical agents (iodine and BaSO4) and a proposed spectral library of contrast agents (Gd2O3, HfO2, and Au). Bisphosphonate-functionalized Au nanoparticles were demonstrated to enhance sensitivity and specificity for the detection of breast microcalcifications by conventional radiography and CT in both normal and dense mammary tissue using murine models. Moreover, photon-counting spectral CT enabled quantitative material decomposition of the Au and calcium signals. Immunoconjugated Au@SiO2 nanoparticles enabled highly-specific targeting of CD133+ ovarian cancer stem cells for contrast-enhanced detection in model tumors.

Molecular magnetic resonance imaging of atherosclerotic vessel wall disease.

PubMed

Nörenberg, Dominik; Ebersberger, Hans U; Diederichs, Gerd; Hamm, Bernd; Botnar, René M; Makowski, Marcus R

2016-03-01

Molecular imaging aims to improve the identification and characterization of pathological processes in vivo by visualizing the underlying biological mechanisms. Molecular imaging techniques are increasingly used to assess vascular inflammation, remodeling, cell migration, angioneogenesis and apoptosis. In cardiovascular diseases, molecular magnetic resonance imaging (MRI) offers new insights into the in vivo biology of pathological vessel wall processes of the coronary and carotid arteries and the aorta. This includes detection of early vascular changes preceding plaque development, visualization of unstable plaques and assessment of response to therapy. The current review focuses on recent developments in the field of molecular MRI to characterise different stages of atherosclerotic vessel wall disease. A variety of molecular MR-probes have been developed to improve the non-invasive detection and characterization of atherosclerotic plaques. Specifically targeted molecular probes allow for the visualization of key biological steps in the cascade leading to the development of arterial vessel wall lesions. Early detection of processes which lead to the development of atherosclerosis and the identification of vulnerable atherosclerotic plaques may enable the early assessment of response to therapy, improve therapy planning, foster the prevention of cardiovascular events and may open the door for the development of patient-specific treatment strategies. Targeted MR-probes allow the characterization of atherosclerosis on a molecular level. Molecular MRI can identify in vivo markers for the differentiation of stable and unstable plaques. Visualization of early molecular changes has the potential to improve patient-individualized risk-assessment.

Comparison of contrast media and low-molecular-weight dextran for frequency-domain optical coherence tomography.

PubMed

Ozaki, Yuichi; Kitabata, Hironori; Tsujioka, Hiroto; Hosokawa, Seiki; Kashiwagi, Manabu; Ishibashi, Kohei; Komukai, Kenichi; Tanimoto, Takashi; Ino, Yasushi; Takarada, Shigeho; Kubo, Takashi; Kimura, Keizo; Tanaka, Atsushi; Hirata, Kumiko; Mizukoshi, Masato; Imanishi, Toshio; Akasaka, Takashi

2012-01-01

Although an intracoronary frequency-domain optical coherence tomography (FD-OCT) system overcomes several limitations of the time-domain OCT (TD-OCT) system, the former requires injection of contrast media for image acquisition. The increased total amount of contrast media for FD-OCT image acquisition may lead to the impairment of renal function. The safety and usefulness of the non-occlusion method with low-molecular-weight dextran L (LMD-L) via a guiding catheter for TD-OCT image acquisition have been reported previously. The aim of the present study was to compare the image quality and quantitative measurements between contrast media and LMD-L for FD-OCT image acquisition in coronary stented lesions. Twenty-two patients with 25 coronary stented lesions were enrolled in this study. FD-OCT was performed with the continuous-flushing method via a guiding catheter. Both contrast media and LMD-L were infused at a rate of 4 ml/s by an autoinjector. With regard to image quality, the prevalence of clear image segments was comparable between contrast media and LMD-L (97.9% vs. 96.5%, P=0.90). Furthermore, excellent correlations were observed between both flushing solutions in terms of minimum lumen area, mean lumen area, and mean stent area. The total volumes of contrast media and of LMD-L needed for OCT image acquisition were similar. FD-OCT image acquisition with LMD-L has the potential to reduce the total amount of contrast media without loss of image quality.

Single-Molecule Real-Time 3D Imaging of the Transcription Cycle by Modulation Interferometry.

PubMed

Wang, Guanshi; Hauver, Jesse; Thomas, Zachary; Darst, Seth A; Pertsinidis, Alexandros

2016-12-15

Many essential cellular processes, such as gene control, employ elaborate mechanisms involving the coordination of large, multi-component molecular assemblies. Few structural biology tools presently have the combined spatial-temporal resolution and molecular specificity required to capture the movement, conformational changes, and subunit association-dissociation kinetics, three fundamental elements of how such intricate molecular machines work. Here, we report a 3D single-molecule super-resolution imaging study using modulation interferometry and phase-sensitive detection that achieves <2 nm axial localization precision, well below the few-nanometer-sized individual protein components. To illustrate the capability of this technique in probing the dynamics of complex macromolecular machines, we visualize the movement of individual multi-subunit E. coli RNA polymerases through the complete transcription cycle, dissect the kinetics of the initiation-elongation transition, and determine the fate of σ 70 initiation factors during promoter escape. Modulation interferometry sets the stage for single-molecule studies of several hitherto difficult-to-investigate multi-molecular transactions that underlie genome regulation. Copyright © 2016 Elsevier Inc. All rights reserved.

The Transferrin Receptor: A Potential Molecular Imaging Marker for Human Cancer1

PubMed Central

Högemann-Savellano, Dagmar; Bos, Erik; Blondet, Cyrille; Sato, Fuminori; Abe, Tatsuya; Josephson, Lee; Weissleder, Ralph; Gaudet, Justin; Sgroi, Dennis; Peters, Peter J.; Basilion, James P.

2003-01-01

Abstract Noninvasive imaging of differences between the molecular properties of cancer and normal tissue has the potential to enhance the detection of tumors. Because overexpression of endogenous transferrin receptor (TfR) has been qualitatively described for various cancers and is presumably due to malignant transformation of cells, TfR may represent a suitable target for application of molecular imaging technologies to increase detection of smaller tumors. In the work reported here, investigation into the biology of this receptor using electron microscopy has demonstrated that iron oxide particles targeted to TfR are internalized and accumulate in lysosomal vesicles within cells. Biochemical analysis of the interaction of imaging probes with cells overexpressing the TfR demonstrated that the extent of accumulation, and therefore probe efficacy, is dependent on the nature of the chemical cross-link between transferrin and the iron oxide particle. These data were utilized to design and synthesize an improved imaging probe. Experiments demonstrate that the novel magnetic resonance imaging (MRI) probe is sensitive enough to detect small differences in endogenous TfR expression in human cancer cell lines. Quantitative measurement of TfR overexpression in a panel of 27 human breast cancer patients demonstrated that 74% of patient cancer tissues overexpressed the TfR and that the sensitivity of the new imaging agent was suitable to detect TfR overexpression in greater than 40% of these cases. Based on a biochemical and cell biological approach, these studies have resulted in the synthesis and development of an improved MRI probe with the best in vitro and in vivo imaging properties reported to date. PMID:14965443

Metabolic Mapping of Breast Cancer with Multiphoton Spectral and Lifetime Imaging

DTIC Science & Technology

2008-03-01

Biomedical Optics May/June 2008 Vol. 133031220-1 the most prevalent cancer among women . 1 Therefore, tech- nologies to detect, classify, study, and...and molecular function using optical imaging: applications to breast cancer,” Breast Cancer Res. Treat. 31, 41–46 2001. 3. M. Sidani , J. Wyckoff

Experimental Study and Numerical Modeling of Gas Flow in Microchannels and Micronozzles

DTIC Science & Technology

2005-12-01

built and used to study gas flows in microscale. Gas velocity measurements in microscale were conducted using both Laser Induced Fluorescence...velocity measurements in microscale were conducted using both Laser Induced Fluorescence technique (LIF) in conjunction with Image Correlation...micronozzles, several velocity measurement techniques have been used, such as laser doppler anemometry (LDA), particle image velocimetry (PIV), molecular

Second harmonic generation imaging - a new method for unraveling molecular information of starch.

PubMed

Zhuo, Zong-Yan; Liao, Chien-Sheng; Huang, Chen-Han; Yu, Jiun-Yann; Tzeng, Yu-Yi; Lo, Wen; Dong, Chen-Yuan; Chui, Hsiang-Chen; Huang, Yu-Chan; Lai, Hsi-Mei; Chu, Shi-Wei

2010-07-01

We present a new method, second harmonic generation (SHG) imaging for the study of starch structure. SHG imaging can provide the structural organization and molecular orientation information of bio-tissues without centrosymmetry. In recent years, SHG has proven its capability in the study of crystallized bio-molecules such as collagen and myosin. Starch, the most important food source and a promising future energy candidate, has, for a decade, been shown to exhibit strong SHG response. By comparing SHG intensity from different starch species, we first identified that the SHG-active molecule is amylopectin, which accounts for the crystallinity in starch granules. With the aid of SHG polarization anisotropy, we extracted the complete χ((2)) tensor of amylopectin, which reflects the underlying molecular details. Through χ((2)) tensor analysis, three-dimensional orientation and packing symmetry of amylopectin are determined. The helical angle of the double-helix in amylopectin is also deduced from the tensor, and the value corresponds well to previous X-ray studies, further verifying amylopectin as SHG source. It is noteworthy that the nm-sized structure of amylopectin inside a starch granule can be determined by this far-field optical method with 1-μm excitation wavelength. Since SHG is a relatively new tool for plant research, a detailed understanding of SHG in starch structure will be useful for future high-resolution imaging and quantitative analyses for food/energy applications. Copyright © 2010 Elsevier Inc. All rights reserved.

Method and apparatus for molecular imaging using x-rays at resonance wavelengths

DOEpatents

Chapline, G.F. Jr.

Holographic x-ray images are produced representing the molecular structure of a microscopic object, such as a living cell, by directing a beam of coherent x-rays upon the object to produce scattering of the x-rays by the object, producing interference on a recording medium between the scattered x-rays from the object and unscattered coherent x-rays and thereby producing holograms on the recording surface, and establishing the wavelength of the coherent x-rays to correspond with a molecular resonance of a constituent of such object and thereby greatly improving the contrast, sensitivity and resolution of the holograms as representations of molecular structures involving such constituent. For example, the coherent x-rays may be adjusted to the molecular resonant absorption line of nitrogen at about 401.3 eV to produce holographic images featuring molecular structures involving nitrogen.

Method and apparatus for molecular imaging using X-rays at resonance wavelengths

DOEpatents

Chapline, Jr., George F.

1985-01-01

Holographic X-ray images are produced representing the molecular structure of a microscopic object, such as a living cell, by directing a beam of coherent X-rays upon the object to produce scattering of the X-rays by the object, producing interference on a recording medium between the scattered X-rays from the object and unscattered coherent X-rays and thereby producing holograms on the recording surface, and establishing the wavelength of the coherent X-rays to correspond with a molecular resonance of a constituent of such object and thereby greatly improving the contrast, sensitivity and resolution of the holograms as representations of molecular structures involving such constituent. For example, the coherent X-rays may be adjusted to the molecular resonant absorption line of nitrogen at about 401.3 eV to produce holographic images featuring molecular structures involving nitrogen.

Multiscale Integration of -Omic, Imaging, and Clinical Data in Biomedical Informatics

PubMed Central

Phan, John H.; Quo, Chang F.; Cheng, Chihwen; Wang, May Dongmei

2016-01-01

This paper reviews challenges and opportunities in multiscale data integration for biomedical informatics. Biomedical data can come from different biological origins, data acquisition technologies, and clinical applications. Integrating such data across multiple scales (e.g., molecular, cellular/tissue, and patient) can lead to more informed decisions for personalized, predictive, and preventive medicine. However, data heterogeneity, community standards in data acquisition, and computational complexity are big challenges for such decision making. This review describes genomic and proteomic (i.e., molecular), histopathological imaging (i.e., cellular/tissue), and clinical (i.e., patient) data; it includes case studies for single-scale (e.g., combining genomic or histopathological image data), multiscale (e.g., combining histopathological image and clinical data), and multiscale and multiplatform (e.g., the Human Protein Atlas and The Cancer Genome Atlas) data integration. Numerous opportunities exist in biomedical informatics research focusing on integration of multiscale and multiplatform data. PMID:23231990

A novel SPECT camera for molecular imaging of the prostate

NASA Astrophysics Data System (ADS)

Cebula, Alan; Gilland, David; Su, Li-Ming; Wagenaar, Douglas; Bahadori, Amir

2011-10-01

The objective of this work is to develop an improved SPECT camera for dedicated prostate imaging. Complementing the recent advancements in agents for molecular prostate imaging, this device has the potential to assist in distinguishing benign from aggressive cancers, to improve site-specific localization of cancer, to improve accuracy of needle-guided prostate biopsy of cancer sites, and to aid in focal therapy procedures such as cryotherapy and radiation. Theoretical calculations show that the spatial resolution/detection sensitivity of the proposed SPECT camera can rival or exceed 3D PET and further signal-to-noise advantage is attained with the better energy resolution of the CZT modules. Based on photon transport simulation studies, the system has a reconstructed spatial resolution of 4.8 mm with a sensitivity of 0.0001. Reconstruction of a simulated prostate distribution demonstrates the focal imaging capability of the system.

Multiscale integration of -omic, imaging, and clinical data in biomedical informatics.

PubMed

Phan, John H; Quo, Chang F; Cheng, Chihwen; Wang, May Dongmei

2012-01-01

This paper reviews challenges and opportunities in multiscale data integration for biomedical informatics. Biomedical data can come from different biological origins, data acquisition technologies, and clinical applications. Integrating such data across multiple scales (e.g., molecular, cellular/tissue, and patient) can lead to more informed decisions for personalized, predictive, and preventive medicine. However, data heterogeneity, community standards in data acquisition, and computational complexity are big challenges for such decision making. This review describes genomic and proteomic (i.e., molecular), histopathological imaging (i.e., cellular/tissue), and clinical (i.e., patient) data; it includes case studies for single-scale (e.g., combining genomic or histopathological image data), multiscale (e.g., combining histopathological image and clinical data), and multiscale and multiplatform (e.g., the Human Protein Atlas and The Cancer Genome Atlas) data integration. Numerous opportunities exist in biomedical informatics research focusing on integration of multiscale and multiplatform data.

Dynamic dual-isotope molecular imaging elucidates principles for optimizing intrathecal drug delivery

PubMed Central

Wolf, Daniel A.; Hesterman, Jacob Y.; Sullivan, Jenna M.; Orcutt, Kelly D.; Silva, Matthew D.; Lobo, Merryl; Wellman, Tyler; Hoppin, Jack

2016-01-01

The intrathecal (IT) dosing route offers a seemingly obvious solution for delivering drugs directly to the central nervous system. However, gaps in understanding drug molecule behavior within the anatomically and kinetically unique environment of the mammalian IT space have impeded the establishment of pharmacokinetic principles for optimizing regional drug exposure along the neuraxis. Here, we have utilized high-resolution single-photon emission tomography with X-ray computed tomography to study the behavior of multiple molecular imaging tracers following an IT bolus injection, with supporting histology, autoradiography, block-face tomography, and MRI. Using simultaneous dual-isotope imaging, we demonstrate that the regional CNS tissue exposure of molecules with varying chemical properties is affected by IT space anatomy, cerebrospinal fluid (CSF) dynamics, CSF clearance routes, and the location and volume of the injected bolus. These imaging approaches can be used across species to optimize the safety and efficacy of IT drug therapy for neurological disorders. PMID:27699254

Functionalized gold nanorods for molecular optoacoustic imaging

NASA Astrophysics Data System (ADS)

Eghtedari, Mohammad; Oraevsky, Alexander; Conjusteau, Andre; Copland, John A.; Kotov, Nicholas A.; Motamedi, Massoud

2007-02-01

The development of gold nanoparticles for molecular optoacoustic imaging is a very promising area of research and development. Enhancement of optoacoustic imaging for molecular detection of tumors requires the engineering of nanoparticles with geometrical and molecular features that can enhance selective targeting of malignant cells while optimizing the sensitivity of optoacoustic detection. In this article, cylindrical gold nanoparticles (i.e. gold nanorods) were fabricated with a plasmon resonance frequency in the near infra-red region of the spectrum, where deep irradiation of tissue is possible using an Alexandrite laser. Gold nanorods (Au-NRs) were functionalized by covalent attachment of Poly(ethylene glycol) to enhance their biocompatibility. These particles were further functionalized with the aim of targeting breast cancer cells using monoclonal antibodies that binds to Her2/neu receptors, which are over expressed on the surface of breast cancer cells. A custom Laser Optoacoustic Imaging System (LOIS) was designed and employed to image nanoparticle-targeted cancer cells in a phantom and PEGylated Au-NRs that were injected subcutaneously into a nude mouse. The results of our experiments show that functionalized Au-NRs with a plasmon resonance frequency at near infra-red region of the spectrum can be detected and imaged in vivo using laser optoacoustic imaging system.

Motion estimation of subcellular structures from fluorescence microscopy images.

PubMed

Vallmitjana, A; Civera-Tregon, A; Hoenicka, J; Palau, F; Benitez, R

2017-07-01

We present an automatic image processing framework to study moving intracellular structures from live cell fluorescence microscopy. The system includes the identification of static and dynamic structures from time-lapse images using data clustering as well as the identification of the trajectory of moving objects with a probabilistic tracking algorithm. The method has been successfully applied to study mitochondrial movement in neurons. The approach provides excellent performance under different experimental conditions and is robust to common sources of noise including experimental, molecular and biological fluctuations.

Compensation of optical heterogeneity-induced artifacts in fluorescence molecular tomography: theory and in vivo validation

NASA Astrophysics Data System (ADS)

Mohajerani, Pouyan; Adibi, Ali; Kempner, Joshua; Yared, Wael

2009-05-01

We present a method for reduction of image artifacts induced by the optical heterogeneities of tissue in fluorescence molecular tomography (FMT) through identification and compensation of image regions that evidence propagation of emission light through thin or low-absorption tunnels in tissue. The light tunneled as such contributes to the emission image as spurious components that might substantially overwhelm the desirable fluorescence emanating from the targeted lesions. The proposed method makes use of the strong spatial correlation between the emission and excitation images to estimate the tunneled components and yield a residual image that mainly consists of the signal due to the desirable fluorescence. This residual image is further refined using a coincidence mask constructed for each excitation-emission image pair. The coincidence mask is essentially a map of the ``hot spots'' that occur in both excitation and emission images, as such areas are often associated with tunneled emission. In vivo studies are performed on a human colon adenocarcinoma xenograft tumor model with subcutaneous tumors and a murine breast adenocarcinoma model with aggressive tumor cell metastasis and growth in the lungs. Results demonstrate significant improvements in the reconstructions achieved by the proposed method.

Validating Intravascular Imaging with Serial Optical Coherence Tomography and Confocal Fluorescence Microscopy.

PubMed

Tardif, Pier-Luc; Bertrand, Marie-Jeanne; Abran, Maxime; Castonguay, Alexandre; Lefebvre, Joël; Stähli, Barbara E; Merlet, Nolwenn; Mihalache-Avram, Teodora; Geoffroy, Pascale; Mecteau, Mélanie; Busseuil, David; Ni, Feng; Abulrob, Abedelnasser; Rhéaume, Éric; L'Allier, Philippe; Tardif, Jean-Claude; Lesage, Frédéric

2016-12-15

Atherosclerotic cardiovascular diseases are characterized by the formation of a plaque in the arterial wall. Intravascular ultrasound (IVUS) provides high-resolution images allowing delineation of atherosclerotic plaques. When combined with near infrared fluorescence (NIRF), the plaque can also be studied at a molecular level with a large variety of biomarkers. In this work, we present a system enabling automated volumetric histology imaging of excised aortas that can spatially correlate results with combined IVUS/NIRF imaging of lipid-rich atheroma in cholesterol-fed rabbits. Pullbacks in the rabbit aortas were performed with a dual modality IVUS/NIRF catheter developed by our group. Ex vivo three-dimensional (3D) histology was performed combining optical coherence tomography (OCT) and confocal fluorescence microscopy, providing high-resolution anatomical and molecular information, respectively, to validate in vivo findings. The microscope was combined with a serial slicer allowing for the imaging of the whole vessel automatically. Colocalization of in vivo and ex vivo results is demonstrated. Slices can then be recovered to be tested in conventional histology.

FMT-XCT: in vivo animal studies with hybrid fluorescence molecular tomography-X-ray computed tomography.

PubMed

Ale, Angelique; Ermolayev, Vladimir; Herzog, Eva; Cohrs, Christian; de Angelis, Martin Hrabé; Ntziachristos, Vasilis

2012-06-01

The development of hybrid optical tomography methods to improve imaging performance has been suggested over a decade ago and has been experimentally demonstrated in animals and humans. Here we examined in vivo performance of a camera-based hybrid fluorescence molecular tomography (FMT) system for 360° imaging combined with X-ray computed tomography (XCT). Offering an accurately co-registered, information-rich hybrid data set, FMT-XCT has new imaging possibilities compared to stand-alone FMT and XCT. We applied FMT-XCT to a subcutaneous 4T1 tumor mouse model, an Aga2 osteogenesis imperfecta model and a Kras lung cancer mouse model, using XCT information during FMT inversion. We validated in vivo imaging results against post-mortem planar fluorescence images of cryoslices and histology data. Besides offering concurrent anatomical and functional information, FMT-XCT resulted in the most accurate FMT performance to date. These findings indicate that addition of FMT optics into the XCT gantry may be a potent upgrade for small-animal XCT systems.

Determining the Molecular Growth Mechanisms of Protein Crystal Faces by Atomic Force Microscopy

NASA Technical Reports Server (NTRS)

Nadarajah, Arunan; Li, Huayu; Pusey, Marc L.

1999-01-01

A high resolution atomic force microscopy (AFM) study had shown that the molecular packing on the tetragonal lysozyme (110) face corresponded to only one of two possible packing arrangements, suggesting that growth layers on this face were of bimolecular height. Theoretical analyses of the packing also indicated that growth of this face should proceed by the addition of growth units of at least tetramer size corresponding to the 43 helices in the crystal. In this study an AFM linescan technique was devised to measure the dimensions of individual growth units on protein crystal faces as they were being incorporated into the lattice. Images of individual growth events on the (110) face of tetragonal lysozyme crystals were observed, shown by jump discontinuities in the growth step in the linescan images as shown in the figure. The growth unit dimension in the scanned direction was obtained from these images. A large number of scans in two directions on the (110) face were performed and the distribution of lysozyme growth unit sizes were obtained. A variety of unit sizes corresponding to 43 helices, were shown to participate in the growth process, with the 43 tetramer being the minimum observed size. This technique represents a new application for AFM allowing time resolved studies of molecular process to be carried out.

New diagnostic methods for laser plasma- and microwave-enhanced combustion

PubMed Central

Miles, Richard B; Michael, James B; Limbach, Christopher M; McGuire, Sean D; Chng, Tat Loon; Edwards, Matthew R; DeLuca, Nicholas J; Shneider, Mikhail N; Dogariu, Arthur

2015-01-01

The study of pulsed laser- and microwave-induced plasma interactions with atmospheric and higher pressure combusting gases requires rapid diagnostic methods that are capable of determining the mechanisms by which these interactions are taking place. New rapid diagnostics are presented here extending the capabilities of Rayleigh and Thomson scattering and resonance-enhanced multi-photon ionization (REMPI) detection and introducing femtosecond laser-induced velocity and temperature profile imaging. Spectrally filtered Rayleigh scattering provides a method for the planar imaging of temperature fields for constant pressure interactions and line imaging of velocity, temperature and density profiles. Depolarization of Rayleigh scattering provides a measure of the dissociation fraction, and multi-wavelength line imaging enables the separation of Thomson scattering from Rayleigh scattering. Radar REMPI takes advantage of high-frequency microwave scattering from the region of laser-selected species ionization to extend REMPI to atmospheric pressures and implement it as a stand-off detection method for atomic and molecular species in combusting environments. Femtosecond laser electronic excitation tagging (FLEET) generates highly excited molecular species and dissociation through the focal zone of the laser. The prompt fluorescence from excited molecular species yields temperature profiles, and the delayed fluorescence from recombining atomic fragments yields velocity profiles. PMID:26170432

Deciphering protein signatures using color, morphological, and topological analysis of immunohistochemically stained human tissues

NASA Astrophysics Data System (ADS)

Zerhouni, Erwan; Prisacari, Bogdan; Zhong, Qing; Wild, Peter; Gabrani, Maria

2016-03-01

Images of tissue specimens enable evidence-based study of disease susceptibility and stratification. Moreover, staining technologies empower the evidencing of molecular expression patterns by multicolor visualization, thus enabling personalized disease treatment and prevention. However, translating molecular expression imaging into direct health benefits has been slow. Two major factors contribute to that. On the one hand, disease susceptibility and progression is a complex, multifactorial molecular process. Diseases, such as cancer, exhibit cellular heterogeneity, impeding the differentiation between diverse grades or types of cell formations. On the other hand, the relative quantification of the stained tissue selected features is ambiguous, tedious and time consuming, prone to clerical error, leading to intra- and inter-observer variability and low throughput. Image analysis of digital histopathology images is a fast-developing and exciting area of disease research that aims to address the above limitations. We have developed a computational framework that extracts unique signatures using color, morphological and topological information and allows the combination thereof. The integration of the above information enables diagnosis of disease with AUC as high as 0.97. Multiple staining show significant improvement with respect to most proteins, and an AUC as high as 0.99.

Functional group selective STM Imaging in self-assembled monolayers: Benzeneselenol on Au(111)

NASA Astrophysics Data System (ADS)

Azzam, Waleed; Zharnikov, Michael; Rohwerde, Michael; Bashir, Asif

2018-01-01

Benzeneselenol (PSe) self-assembled monolayers (SAMs) formed on Au(111) substrate by the immersion procedure with an immersion time of 24 h and 4 weeks were studied by high-resolution scanning tunneling microscopy (STM). The short molecular rows, which have been previously attributed to irregular translational domains, were found to be regularly repeated within a single domain in the SAMs fabricated upon the immersion for 4 weeks, forming adlayer structure with a very large unit cell. This structure could be assigned as a (27 × 5) superlattice (α phase) containing 36 molecules in the oblique unit cell. This phase coexisted with a different phase having a commensurate (8√{ 3 } × 4) superstructure (β phase) containing 28 protrusions per rectangular unit cell. Analysis of the STM images suggested that each PSe molecule in the β phase was imaged not as one but as a pair of protrusions, which were attributed to the benzene ring and the selenium headgroup of the PSe molecule. At the given molecular length, the spacing between the protrusions defined the molecular tilt, allowing us to derive the orientation of the SAM constituents directly from the STM image.

Application of molecular imaging technology in evaluating the inhibiting effect of apigenin in vivo on subcutaneous hepatocellular carcinoma.

PubMed

Li, Gang; Chi, Chong-Wei; Shao, Xian-Fang; Fang, Chi-Hua

2017-05-20

The aim of this study was to evaluate the inhibiting effect of apigenin on liver cancer in vivo based on the optical molecular imaging method. Subcutaneous liver tumor models were established using respective 1 × 10 6 firefly luciferase (fLuc) and green fluorescent protein (GFP) labeled human hepatocellular carcinoma cells (HepG2-fLuc and HepG2-GFP cells) in 20 BALB/c nude mice which were randomly divided into two groups, 10 in each group. After the tumor cells were implanted 15 days, apigenin was administered through intraperitoneal injection in group B, the other ten mice as control group A. Bioluminescence imaging (BLI) and fluorescence molecular imaging (FMI) were carried out for the follow-up of subcutaneous tumor model. As time goes on, intensity and distribution of bioluminescence and fluorescence of tumours increased gradually with the growth of tumours little by little. The whole process of observation was in accordance with known activities of HCC in the human liver. The tumor volume and tumor weight were significant lower in group B than in group A (p < 0.05), Subcutaneous tumours in the apigenin treatment group B based on BLI and FMI were significantly inhibited compared to the control group A (p < 0.05). Apigenin could be expected as a new drug to treat hepatocellular carcinoma. Optical molecular imaging technology enabled the non-invasive and reliable assessment of anti-tumor drug efficacy on liver cancer. Copyright © 2017 Elsevier Inc. All rights reserved.

In vivo nanoparticle imaging of innate immune cells can serve as a marker of disease severity in a model of multiple sclerosis.

PubMed

Kirschbaum, Klara; Sonner, Jana K; Zeller, Matthias W; Deumelandt, Katrin; Bode, Julia; Sharma, Rakesh; Krüwel, Thomas; Fischer, Manuel; Hoffmann, Angelika; Costa da Silva, Milene; Muckenthaler, Martina U; Wick, Wolfgang; Tews, Björn; Chen, John W; Heiland, Sabine; Bendszus, Martin; Platten, Michael; Breckwoldt, Michael O

2016-11-15

Innate immune cells play a key role in the pathogenesis of multiple sclerosis and experimental autoimmune encephalomyelitis (EAE). Current clinical imaging is restricted to visualizing secondary effects of inflammation, such as gliosis and blood-brain barrier disruption. Advanced molecular imaging, such as iron oxide nanoparticle imaging, can allow direct imaging of cellular and molecular activity, but the exact cell types that phagocytose nanoparticles in vivo and how phagocytic activity relates to disease severity is not well understood. In this study we used MRI to map inflammatory infiltrates using high-field MRI and fluorescently labeled cross-linked iron oxide nanoparticles for cell tracking. We confirmed nanoparticle uptake and MR detectability ex vivo. Using in vivo MRI, we identified extensive nanoparticle signal in the cerebellar white matter and circumscribed cortical gray matter lesions that developed during the disease course (4.6-fold increase of nanoparticle accumulation in EAE compared with healthy controls, P < 0.001). Nanoparticles showed good cellular specificity for innate immune cells in vivo, labeling activated microglia, infiltrating macrophages, and neutrophils, whereas there was only sparse uptake by adaptive immune cells. Importantly, nanoparticle signal correlated better with clinical disease than conventional gadolinium (Gd) imaging (r, 0.83 for nanoparticles vs. 0.71 for Gd-imaging, P < 0.001). We validated our approach using the Food and Drug Administration-approved iron oxide nanoparticle ferumoxytol. Our results show that noninvasive molecular imaging of innate immune responses can serve as an imaging biomarker of disease activity in autoimmune-mediated neuroinflammation with potential clinical applications in a wide range of inflammatory diseases.

Review of fluorescence guided surgery systems: identification of key performance capabilities beyond indocyanine green imaging

PubMed Central

DSouza, Alisha V.; Lin, Huiyun; Henderson, Eric R.; Samkoe, Kimberley S.; Pogue, Brian W.

2016-01-01

Abstract. There is growing interest in using fluorescence imaging instruments to guide surgery, and the leading options for open-field imaging are reviewed here. While the clinical fluorescence-guided surgery (FGS) field has been focused predominantly on indocyanine green (ICG) imaging, there is accelerated development of more specific molecular tracers. These agents should help advance new indications for which FGS presents a paradigm shift in how molecular information is provided for resection decisions. There has been a steady growth in commercially marketed FGS systems, each with their own differentiated performance characteristics and specifications. A set of desirable criteria is presented to guide the evaluation of instruments, including: (i) real-time overlay of white-light and fluorescence images, (ii) operation within ambient room lighting, (iii) nanomolar-level sensitivity, (iv) quantitative capabilities, (v) simultaneous multiple fluorophore imaging, and (vi) ergonomic utility for open surgery. In this review, United States Food and Drug Administration 510(k) cleared commercial systems and some leading premarket FGS research systems were evaluated to illustrate the continual increase in this performance feature base. Generally, the systems designed for ICG-only imaging have sufficient sensitivity to ICG, but a fraction of the other desired features listed above, with both lower sensitivity and dynamic range. In comparison, the emerging research systems targeted for use with molecular agents have unique capabilities that will be essential for successful clinical imaging studies with low-concentration agents or where superior rejection of ambient light is needed. There is no perfect imaging system, but the feature differences among them are important differentiators in their utility, as outlined in the data and tables here. PMID:27533438

Review of fluorescence guided surgery systems: identification of key performance capabilities beyond indocyanine green imaging

NASA Astrophysics Data System (ADS)

DSouza, Alisha V.; Lin, Huiyun; Henderson, Eric R.; Samkoe, Kimberley S.; Pogue, Brian W.

2016-08-01

There is growing interest in using fluorescence imaging instruments to guide surgery, and the leading options for open-field imaging are reviewed here. While the clinical fluorescence-guided surgery (FGS) field has been focused predominantly on indocyanine green (ICG) imaging, there is accelerated development of more specific molecular tracers. These agents should help advance new indications for which FGS presents a paradigm shift in how molecular information is provided for resection decisions. There has been a steady growth in commercially marketed FGS systems, each with their own differentiated performance characteristics and specifications. A set of desirable criteria is presented to guide the evaluation of instruments, including: (i) real-time overlay of white-light and fluorescence images, (ii) operation within ambient room lighting, (iii) nanomolar-level sensitivity, (iv) quantitative capabilities, (v) simultaneous multiple fluorophore imaging, and (vi) ergonomic utility for open surgery. In this review, United States Food and Drug Administration 510(k) cleared commercial systems and some leading premarket FGS research systems were evaluated to illustrate the continual increase in this performance feature base. Generally, the systems designed for ICG-only imaging have sufficient sensitivity to ICG, but a fraction of the other desired features listed above, with both lower sensitivity and dynamic range. In comparison, the emerging research systems targeted for use with molecular agents have unique capabilities that will be essential for successful clinical imaging studies with low-concentration agents or where superior rejection of ambient light is needed. There is no perfect imaging system, but the feature differences among them are important differentiators in their utility, as outlined in the data and tables here.

[Situation of supply and boom of PET imaging: what is the future for technetium-99m in nuclear medicine?].

PubMed

Maia, S; Ayachi Hatit, N; Paycha, F

2011-05-01

Molecular imaging has shown its interest in the diagnosis, staging and therapy monitoring of many diseases, especially in the field of cancer. This imaging modality can detect non-invasively early molecular changes specific to these diseases. Its expansion includes two aspects linked firstly with the advanced techniques of imaging modalities and secondly with the development of tracers as radio pharmaceuticals for imaging new molecular targets. Technetium-99m ((99m)Tc), because of its physical characteristics, its widespread availability and low cost, is the most used radionuclide in molecular imaging with the technique of single photon emission computed tomography (SPECT). Nevertheless, the current difficulty concerning the supply and the great interest of Positron Emission Tomography (PET), the "competitor" imaging modality-using molecules labelled with fluorine-18 ((18)F), legitimates the question about the future of (99m)Tc, its supremacy and the emergence of new tracer labelled with (99m)Tc. Focusing on the actual and future supply situation, the place of SPECT imaging in nuclear medicine, as well as the development of new molecules labelled with (99m)Tc is necessary to show that this radionuclide will remain essential for the speciality in the next years. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

Dual tracer imaging of SPECT and PET probes in living mice using a sequential protocol

PubMed Central

Chapman, Sarah E; Diener, Justin M; Sasser, Todd A; Correcher, Carlos; González, Antonio J; Avermaete, Tony Van; Leevy, W Matthew

2012-01-01

Over the past 20 years, multimodal imaging strategies have motivated the fusion of Positron Emission Tomography (PET) or Single Photon Emission Computed Tomography (SPECT) scans with an X-ray computed tomography (CT) image to provide anatomical information, as well as a framework with which molecular and functional images may be co-registered. Recently, pre-clinical nuclear imaging technology has evolved to capture multiple SPECT or multiple PET tracers to further enhance the information content gathered within an imaging experiment. However, the use of SPECT and PET probes together, in the same animal, has remained a challenge. Here we describe a straightforward method using an integrated trimodal imaging system and a sequential dosing/acquisition protocol to achieve dual tracer imaging with 99mTc and 18F isotopes, along with anatomical CT, on an individual specimen. Dosing and imaging is completed so that minimal animal manipulations are required, full trimodal fusion is conserved, and tracer crosstalk including down-scatter of the PET tracer in SPECT mode is avoided. This technique will enhance the ability of preclinical researchers to detect multiple disease targets and perform functional, molecular, and anatomical imaging on individual specimens to increase the information content gathered within longitudinal in vivo studies. PMID:23145357

SYMPOSIUM ON MULTIMODALITY CARDIOVASCULAR MOLECULAR IMAGING IMAGING TECHNOLOGY - PART 2

PubMed Central

de Kemp, Robert A.; Epstein, Frederick H.; Catana, Ciprian; Tsui, Benjamin M.W.; Ritman, Erik L.

2013-01-01

Rationale The ability to trace or identify specific molecules within a specific anatomic location provides insight into metabolic pathways, tissue components and tracing of solute transport mechanisms. With the increasing use of small animals for research such imaging must have sufficiently high spatial resolution to allow anatomic localization as well as sufficient specificity and sensitivity to provide an accurate description of the molecular distribution and concentration. Methods Imaging methods based on electromagnetic radiation, such as PET, SPECT, MRI and CT, are increasingly applicable due to recent advances in novel scanner hardware, image reconstruction software and availability of novel molecules which have enhanced sensitivity in these methodologies. Results Micro-PET has been advanced by development of detector arrays that provide higher resolution and positron emitting elements that allow new molecular tracers to be labeled. Micro-MRI has been improved in terms of spatial resolution and sensitivity by increased magnet field strength and development of special purpose coils and associated scan protocols. Of particular interest is the associated ability to image local mechanical function and solute transport processes which can be directly related to the molecular information. This is further strengthened by the synergistic integration of the PET with MRI. Micro-SPECT has been improved by use of coded aperture imaging approaches as well as image reconstruction algorithms which can better deal with the photon limited scan data. The limited spatial resolution can be partially overcome by integrating the SPECT with CT. Micro-CT by itself provides exquisite spatial resolution of anatomy, but recent developments of high spatial resolution photon counting and spectrally-sensitive imaging arrays, combined with x-ray optical devices, have promise for actual molecular identification by virtue of the chemical bond lengths of molecules, especially of bio-polymers. Conclusion With the increasing use of small animals for evaluating new clinical imaging techniques as well as providing increased insights into patho-physiological phenomena, the availability of improved detection systems, scanning protocols and associated software, the repertoire of molecular imaging is greatly increased in sensitivity and specificity. PMID:20457793

Method for imaging informational biological molecules on a semiconductor substrate

NASA Technical Reports Server (NTRS)

Coles, L. Stephen (Inventor)

1994-01-01

Imaging biological molecules such as DNA at rates several times faster than conventional imaging techniques is carried out using a patterned silicon wafer having nano-machined grooves which hold individual molecular strands and periodically spaced unique bar codes permitting repeatably locating all images. The strands are coaxed into the grooves preferably using gravity and pulsed electric fields which induce electric charge attraction to the molecular strands in the bottom surfaces of the grooves. Differential imaging removes substrate artifacts.

Biocompatible Nanocomplexes for Molecular Targeted MRI Contrast Agent

NASA Astrophysics Data System (ADS)

Chen, Zhijin; Yu, Dexin; Wang, Shaojie; Zhang, Na; Ma, Chunhong; Lu, Zaijun

2009-07-01

Accurate diagnosis in early stage is vital for the treatment of Hepatocellular carcinoma. The aim of this study was to investigate the potential of poly lactic acid-polyethylene glycol/gadolinium-diethylenetriamine-pentaacetic acid (PLA-PEG/Gd-DTPA) nanocomplexes using as biocompatible molecular magnetic resonance imaging (MRI) contrast agent. The PLA-PEG/Gd-DTPA nanocomplexes were obtained using self-assembly nanotechnology by incubation of PLA-PEG nanoparticles and the commercial contrast agent, Gd-DTPA. The physicochemical properties of nanocomplexes were measured by atomic force microscopy and photon correlation spectroscopy. The T1-weighted MR images of the nanocomplexes were obtained in a 3.0 T clinical MR imager. The stability study was carried out in human plasma and the distribution in vivo was investigated in rats. The mean size of the PLA-PEG/Gd-DTPA nanocomplexes was 187.9 ± 2.30 nm, and the polydispersity index was 0.108, and the zeta potential was -12.36 ± 3.58 mV. The results of MRI test confirmed that the PLA-PEG/Gd-DTPA nanocomplexes possessed the ability of MRI, and the direct correlation between the MRI imaging intensities and the nano-complex concentrations was observed ( r = 0.987). The signal intensity was still stable within 2 h after incubation of the nanocomplexes in human plasma. The nanocomplexes gave much better image contrast effects and longer stagnation time than that of commercial contrast agent in rat liver. A dose of 0.04 mmol of gadolinium per kilogram of body weight was sufficient to increase the MRI imaging intensities in rat livers by five-fold compared with the commercial Gd-DTPA. PLA-PEG/Gd-DTPA nanocomplexes could be prepared easily with small particle sizes. The nanocomplexes had high plasma stability, better image contrast effect, and liver targeting property. These results indicated that the PLA-PEG/Gd-DTPA nanocomplexes might be potential as molecular targeted imaging contrast agent.

Molecular imaging of tumor blood vessels in prostate cancer.

PubMed

Tilki, Derya; Seitz, Michael; Singer, Bernhard B; Irmak, Ster; Stief, Christian G; Reich, Oliver; Ergün, Süleyman

2009-05-01

In the past three decades many efforts have been undertaken to understand the mechanisms of tumor angiogenesis. The introduction of anti-angiogenic drugs in tumor therapy during the last few years necessitates the establishment of new techniques enabling molecular imaging of tumor vascular remodelling. The determination of tumor size as commonly used is not appropriate since the extended necrosis under anti-angiogenic therapy does not necessarily result in the reduction of tumor diameter. The basis for the molecular imaging of tumor blood vessels is the remodelling of the tumor vessels under anti-angiogenic therapy which obviously occurs at an early stage and seems to be a convincing parameter. Beside the enormous progress in this field during the last few years the resolution is still not high enough to evaluate the remodelling of the micro tumor vessels. New imaging approaches combining specific molecular markers for tumor vessels with the different imaging techniques are needed to overcome this issue as exemplarily discussed for prostate cancer in this review. Molecular contrast agents targeting the vasculature will allow clinicians the visualization of vascular remodelling processes taking place under anti-angiogenic therapy and improve tumor diagnosis and follow-up.

Small Talk: Children's Everyday `Molecule' Ideas

NASA Astrophysics Data System (ADS)

Jakab, Cheryl

2013-08-01

This paper reports on 6-11-year-old children's `sayings and doings' (Harré 2002) as they explore molecule artefacts in dialectical-interactive teaching interviews (Fleer, Cultural Studies of Science Education 3:781-786, 2008; Hedegaard et al. 2008). This sociocultural study was designed to explore children's everyday awareness of and meaning-making with cultural molecular artefacts. Our everyday world is populated with an ever increasing range of molecular or nanoworld words, symbols, images, and games. What do children today say about these artefacts that are used to represent molecular world entities? What are the material and social resources that can influence a child's everyday and developing scientific ideas about `molecules'? How do children interact with these cognitive tools when given expert assistance? What meaning-making is afforded when children are socially and materially assisted in using molecular tools in early chemical and nanoworld thinking? Tool-dependent discursive studies show that provision of cultural artefacts can assist and direct developmental thinking across many domains of science (Schoultz et al., Human Development 44:103-118, 2001; Siegal 2008). Young children's use of molecular artefacts as cognitive tools has not received much attention to date (Jakab 2009a, b). This study shows 6-11-year-old children expressing everyday ideas of molecular artefacts and raising their own questions about the artefacts. They are seen beginning to domesticate (Erneling 2010) the words, symbols, and images to their own purposes when given the opportunity to interact with such artefacts in supported activity. Discursive analysis supports the notion that using `molecules' as cultural tools can help young children to begin `putting on molecular spectacles' (Kind 2004). Playing with an interactive game (ICT) is shown to be particularly helpful in assisting children's early meaning-making with representations of molecules, atoms, and their chemical symbols.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pandit, Shubhrangshu; Preston, Thomas J.; Orr-Ewing, Andrew J., E-mail: a.orr-ewing@bristol.ac.uk

Photodissociation of gaseous bromocyclopropane via its A-band continuum has been studied at excitation wavelengths ranging from 230 nm to 267 nm. Velocity-map images of ground-state bromine atoms (Br), spin-orbit excited bromine atoms (Br{sup ∗}), and C{sub 3}H{sub 5} hydrocarbon radicals reveal the kinetic energies of these various photofragments. Both Br and Br{sup ∗} atoms are predominantly generated via repulsive excited electronic states in a prompt photodissociation process in which the hydrocarbon co-fragment is a cyclopropyl radical. However, the images obtained at the mass of the hydrocarbon radical fragment identify a channel with total kinetic energy greater than that deduced frommore » the Br and Br{sup ∗} images, and with a kinetic energy distribution that exceeds the energetic limit for Br + cyclopropyl radical products. The velocity-map images of these C{sub 3}H{sub 5} fragments have lower angular anisotropies than measured for Br and Br{sup ∗}, indicating molecular restructuring during dissociation. The high kinetic energy C{sub 3}H{sub 5} signals are assigned to allyl radicals generated by a minor photochemical pathway which involves concerted C–Br bond dissociation and cyclopropyl ring-opening following single ultraviolet (UV)-photon absorption. Slow photofragments also contribute to the velocity map images obtained at the C{sub 3}H{sub 5} radical mass, but the corresponding slow Br atoms are not observed. These features in the images are attributed to C{sub 3}H{sub 5}{sup +} from the photodissociation of the C{sub 3}H{sub 5}Br{sup +} molecular cation following two-photon ionization of the parent compound. This assignment is confirmed by 118-nm vacuum ultraviolet ionization studies that prepare the molecular cation in its ground electronic state prior to UV photodissociation.« less

Evidence for concerted ring opening and C-Br bond breaking in UV-excited bromocyclopropane.

PubMed

Pandit, Shubhrangshu; Preston, Thomas J; King, Simon J; Vallance, Claire; Orr-Ewing, Andrew J

2016-06-28

Photodissociation of gaseous bromocyclopropane via its A-band continuum has been studied at excitation wavelengths ranging from 230 nm to 267 nm. Velocity-map images of ground-state bromine atoms (Br), spin-orbit excited bromine atoms (Br(∗)), and C3H5 hydrocarbon radicals reveal the kinetic energies of these various photofragments. Both Br and Br(∗) atoms are predominantly generated via repulsive excited electronic states in a prompt photodissociation process in which the hydrocarbon co-fragment is a cyclopropyl radical. However, the images obtained at the mass of the hydrocarbon radical fragment identify a channel with total kinetic energy greater than that deduced from the Br and Br(∗) images, and with a kinetic energy distribution that exceeds the energetic limit for Br + cyclopropyl radical products. The velocity-map images of these C3H5 fragments have lower angular anisotropies than measured for Br and Br(∗), indicating molecular restructuring during dissociation. The high kinetic energy C3H5 signals are assigned to allyl radicals generated by a minor photochemical pathway which involves concerted C-Br bond dissociation and cyclopropyl ring-opening following single ultraviolet (UV)-photon absorption. Slow photofragments also contribute to the velocity map images obtained at the C3H5 radical mass, but the corresponding slow Br atoms are not observed. These features in the images are attributed to C3H5 (+) from the photodissociation of the C3H5Br(+) molecular cation following two-photon ionization of the parent compound. This assignment is confirmed by 118-nm vacuum ultraviolet ionization studies that prepare the molecular cation in its ground electronic state prior to UV photodissociation.

Small-Animal Molecular Imaging for Preclinical Cancer Research: .μPET and μ.SPECT.

PubMed

Cuccurullo, Vincenzo; Di Stasio, Giuseppe D; Schillirò, Maria L; Mansi, Luigi

2016-01-01

Due to different sizes of humans and rodents, the performance of clinical imaging devices is not enough for a scientifically reliable evaluation in mice and rats; therefore dedicated small-animal systems with a much higher sensitivity and spatial resolution, compared to the ones used in humans, are required. Smallanimal imaging represents a cutting-edge research method able to approach an enormous variety of pathologies in which animal models of disease may be used to elucidate the mechanisms underlying the human condition and/or to allow a translational pharmacological (or other) evaluation of therapeutic tools. Molecular imaging, avoiding animal sacrifice, permits repetitive (i.e. longitudinal) studies on the same animal which becomes its own control. In this way also the over time evaluation of disease progression or of the treatment response is enabled. Many different rodent models have been applied to study almost all kind of human pathologies or to experiment a wide series of drugs and/or other therapeutic instruments. In particular, relevant information has been achieved in oncology by in vivo neoplastic phenotypes, obtained through procedures such as subcutaneous tumor grafts, surgical transplantation of solid tumor, orthotopic injection of tumor cells into specific organs/sites of interest, genetic modification of animals to promote tumor-genesis; in this way traditional or innovative treatments, also including gene therapy, of animals with a cancer induced by a known carcinogen may be experimented. Each model has its own disadvantage but, comparing different studies, it is possible to achieve a panoramic and therefore substantially reliable view on the specific subject. Small-animal molecular imaging has become an invaluable component of modern biomedical research that will gain probably an increasingly important role in the next few years.

Macromolecular powder diffraction : structure solution via molecular.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Doebbler, J.; Von Dreele, R.; X-Ray Science Division

Macromolecular powder diffraction is a burgeoning technique for protein structure solution - ideally suited for cases where no suitable single crystals are available. Over the past seven years, pioneering work by Von Dreele et al. [1,2] and Margiolaki et al. [3,4] has demonstrated the viability of this approach for several protein structures. Among these initial powder studies, molecular replacement solutions of insulin and turkey lysozyme into alternate space groups were accomplished. Pressing the technique further, Margiolaki et al. [5] executed the first molecular replacement of an unknown protein structure: the SH3 domain of ponsin, using data from a multianalyzer diffractometer.more » To demonstrate that cross-species molecular replacement using image plate data is also possible, we present the solution of hen egg white lysozyme using the 60% identical human lysozyme (PDB code: 1LZ1) as the search model. Due to the high incidence of overlaps in powder patterns, especially in more complex structures, we have used extracted intensities from five data sets taken at different salt concentrations in a multi-pattern Pawley refinement. The use of image plates severely increases the overlap problem due to lower detector resolution, but radiation damage effects are minimized with shorter exposure times and the fact that the entire pattern is obtained in a single exposure. This image plate solution establishes the robustness of powder molecular replacement resulting from different data collection techniques.« less

[Correlations between apparent diffusion coefficient in diffusion?weighted magnetic resonance imaging and molecular subtypes of invasive breast cancer masses].

PubMed

Shang, Liu-Tong; Yang, Jia-Fei; Lu, Jing; Wang, Ting-Ting; Zhou, Ying; Xing, Xin-Bo; Wang, Xin-Kun; Yang, Shu-Hui; Hu, Ming-Yan

2017-10-20

To study the correlation of apparent diffusion coefficient (ADC) measured by diffusion-weighted magnetic resonance imaging (MRI) with the molecular subtypes and biological prognostic factors of invasive breast cancer masses. Breast MRI data (including dynamic enhanced and diffusion-weighted imaging) were collected from 64 patients with pathologically confirmed invasive breast cancer masses (a total of 69 lesions). The mean ADC values of the lesions were calculated and their correlations were analyzed with the 5 molecular subtypes of invasive breast cancer and the biological prognostic factors including estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor 2 (HER2), and Ki-67 index. The ADC values did not differ significantly among the 5 molecular subtypes of invasive breast cancer masses (P>0.05) or among lesions with different ER, PR, or HER2 status (P>0.05). The mean ADC values were significantly higher in Ki-67-positive lesions than in the negative lesions (P=0.023 and negatively correlated with the expressions of Ki-67 (r=-0.249). ADC value can not be used to identify the molecular subtypes of invasive breast cancer masses or to evaluate the biological prognosis of the lesions, but its correlation with Ki-67 expression may help in prognostic evaluation and guiding clinical therapy of the tumors.

Ultrasonic Characteristics and Cellular Properties of Anabaena Gas Vesicles.

PubMed

Yang, Yaoheng; Qiu, Zhihai; Hou, Xuandi; Sun, Lei

2017-12-01

Ultrasound imaging is a common modality in clinical examination and biomedical research, but has not played a significant role in molecular imaging for lack of an appropriate contrast agent. Recently, biogenic gas vesicles (GVs), naturally formed by cyanobacteria and haloarchaea, have exhibited great potential as an ultrasound molecular imaging probe with a much smaller size (∼100 nm) and improved imaging contrast. However, the basic acoustic and biological properties of GVs remain unclear, which hinders future application. Here, we studied the fundamental acoustic properties of a rod-shaped gas vesicle from Anabaena, a kind of cyanobacterium, including attenuation, oscillation resonance, and scattering, as well as biological behaviors (cellular internalization and cytotoxicity). We found that GVs have two resonance peaks (85 and 120 MHz). We also observed a significant non-linear effect and its pressure dependence as well. Ultrasound B-mode imaging reveals sufficient echogenicity of GVs for ultrasound imaging enhancement at high frequencies. Biological characterization also reveals endocytosis and non-toxicity. Copyright © 2017 World Federation for Ultrasound in Medicine and Biology. Published by Elsevier Inc. All rights reserved.

Magnetic resonance guided optical spectroscopy imaging of human breast cancer using a combined frequency domain and continuous wave approach

NASA Astrophysics Data System (ADS)

Mastanduno, Michael A.; Davis, Scott C.; Jiang, Shudong; diFlorio-Alexander, Roberta; Pogue, Brian W.; Paulsen, Keith D.

2012-03-01

Dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) is used to image high-risk patients for breast cancer because of its higher sensitivity to tumors (approaching 100%) than traditional x-ray mammography. We focus on Near Infrared Spectroscopy (NIRS) as an emerging functional and molecular imaging technique that non-invasively quantifies optical properties of total hemoglobin, oxygen saturation, water content, scattering, and lipid concentration to increase the relatively low specificity of DCE-MRI. Our optical imaging system combines six frequency domain wavelengths, measured using PMT detectors with three continuous wave wavelengths measured using CCD/spectrometers. We present methods on combining the synergistic attributes of DCE-MR and NIRS for in-vivo imaging of breast cancer in three dimensions using a custom optical MR breast coil and diffusion based light modeling software, NIRFAST. We present results from phantom studies, healthy subjects, and breast cancer patients. Preliminary results show contrast recovery within 10% in phantoms and spatial resolution less than 5mm. Images from healthy subjects were recovered with properties similar to literature values and previous studies. Patient images have shown elevated total hemoglobin values and water fraction, agreeing with histology and previous results. The additional information gained from NIRS may improve the ability to distinguish between malignant and benign lesions during MR imaging. These dual modality instruments will provide complex anatomical and molecular prognostic information, and may decrease the number of biopsies, thereby improving patient care.

High-resolution and high sensitivity mesoscopic fluorescence tomography based on de-scanning EMCCD: System design and thick tissue imaging applications

NASA Astrophysics Data System (ADS)

Ozturk, Mehmet Saadeddin

Optical microscopy has been one of the essential tools for biological studies for decades, however, its application areas was limited to superficial investigation due to strong scattering in live tissues. Even though advanced techniques such as confocal or multiphoton methods have been recently developed to penetrate beyond a few hundreds of microns deep in tissues, they still cannot perform in the mesoscopic regime (millimeter scale) without using destructive sample preparation protocols such as clearing techniques. They provide rich cellular information; however, they cannot be readily employed to investigate the biological processes at larger scales. Herein, we will present our effort to establish a novel imaging approach that can quantify molecular expression in intact tissues, well beyond the current microscopy depth limits. Mesoscopic Fluorescence Molecular Tomography (MFMT) is an emerging imaging modality that offers unique potential for the non-invasive molecular assessment of thick in-vitro and in-vivo live tissues. This novel imaging modality is based on an optical inverse problem that allows for retrieval of the quantitative spatial distribution of fluorescent tagged bio-markers at millimeter depth. MFMT is well-suited for in-vivo subsurface tissue imaging and thick bio-printed specimens due to its high sensitivity and fast acquisition times, as well as relatively large fields of view. Herein, we will first demonstrate the potential of this technique using our first generation MFMT system applied to multiplexed reporter gene imaging (in-vitro) and determination of Photodynamic Therapy (PDT) agent bio-distribution in a mouse model (in-vivo). Second, we will present the design rationale, in silico benchmarking, and experimental validation of a second generation MFMT (2GMFMT) system. We will demonstrate the gain in resolution and sensitivity achieved due to the de-scanned dense detector configuration implemented. The potential of this novel platform will be showcased by applying it to the longitudinal assessment of Ink-Jet Bio-Printed tumor models. This preliminary investigation focuses on monitoring four patient-derived glioblastoma multiforme (GBM) spheroids within their bioreactor for up to 70 days and following their volume change prior to and after exposure to a cytotoxic drug. Overall, our studies indicate that 2GMFMT is a powerful technique for in-vitro and in-vivo thick tissue molecular imaging applications due to its high resolution, fast tomographic imaging capability, and high sensitivity.

Fluorescent and Lanthanide Labeling for Ligand Screens, Assays, and Imaging

PubMed Central

Josan, Jatinder S.; De Silva, Channa R.; Yoo, Byunghee; Lynch, Ronald M.; Pagel, Mark D.; Vagner, Josef; Hruby, Victor J.

2012-01-01

The use of fluorescent (or luminescent) and metal contrast agents in high-throughput screens, in vitro assays, and molecular imaging procedures has rapidly expanded in recent years. Here we describe the development and utility of high-affinity ligands for cancer theranostics and other in vitro screening studies. In this context, we also illustrate the syntheses and use of heteromultivalent ligands as targeted imaging agents. PMID:21318902

A Targeting Microbubble for Ultrasound Molecular Imaging

PubMed Central

Yeh, James Shue-Min; Sennoga, Charles A.; McConnell, Ellen; Eckersley, Robert; Tang, Meng-Xing; Nourshargh, Sussan; Seddon, John M.; Haskard, Dorian O.; Nihoyannopoulos, Petros

2015-01-01

Rationale Microbubbles conjugated with targeting ligands are used as contrast agents for ultrasound molecular imaging. However, they often contain immunogenic (strept)avidin, which impedes application in humans. Although targeting bubbles not employing the biotin-(strept)avidin conjugation chemistry have been explored, only a few reached the stage of ultrasound imaging in vivo, none were reported/evaluated to show all three of the following properties desired for clinical applications: (i) low degree of non-specific bubble retention in more than one non-reticuloendothelial tissue; (ii) effective for real-time imaging; and (iii) effective for acoustic quantification of molecular targets to a high degree of quantification. Furthermore, disclosures of the compositions and methodologies enabling reproduction of the bubbles are often withheld. Objective To develop and evaluate a targeting microbubble based on maleimide-thiol conjugation chemistry for ultrasound molecular imaging. Methods and Results Microbubbles with a previously unreported generic (non-targeting components) composition were grafted with anti-E-selectin F(ab’)2 using maleimide-thiol conjugation, to produce E-selectin targeting microbubbles. The resulting targeting bubbles showed high specificity to E-selectin in vitro and in vivo. Non-specific bubble retention was minimal in at least three non-reticuloendothelial tissues with inflammation (mouse heart, kidneys, cremaster). The bubbles were effective for real-time ultrasound imaging of E-selectin expression in the inflamed mouse heart and kidneys, using a clinical ultrasound scanner. The acoustic signal intensity of the targeted bubbles retained in the heart correlated strongly with the level of E-selectin expression (|r|≥0.8), demonstrating a high degree of non-invasive molecular quantification. Conclusions Targeting microbubbles for ultrasound molecular imaging, based on maleimide-thiol conjugation chemistry and the generic composition described, may possess properties (i)–(iii) desired for clinical applications. PMID:26161541

Stimulated Raman photoacoustic imaging

PubMed Central

Yakovlev, Vladislav V.; Zhang, Hao F.; Noojin, Gary D.; Denton, Michael L.; Thomas, Robert J.; Scully, Marlan O.

2010-01-01

Achieving label-free, molecular-specific imaging with high spatial resolution in deep tissue is often considered the grand challenge of optical imaging. To accomplish this goal, significant optical scattering in tissues has to be overcome while achieving molecular specificity without resorting to extrinsic labeling. We demonstrate the feasibility of developing such an optical imaging modality by combining the molecularly specific stimulated Raman excitation with the photoacoustic detection. By employing two ultrashort excitation laser pulses, separated in frequency by the vibrational frequency of a targeted molecule, only the specific vibrational level of the target molecules in the illuminated tissue volume is excited. This targeted optical absorption generates ultrasonic waves (referred to as stimulated Raman photoacoustic waves) which are detected using a traditional ultrasonic transducer to form an image following the design of the established photoacoustic microscopy. PMID:21059930

Dual-modality, fluorescent, PLGA encapsulated bismuth nanoparticles for molecular and cellular fluorescence imaging and computed tomography

NASA Astrophysics Data System (ADS)

Swy, Eric R.; Schwartz-Duval, Aaron S.; Shuboni, Dorela D.; Latourette, Matthew T.; Mallet, Christiane L.; Parys, Maciej; Cormode, David P.; Shapiro, Erik M.

2014-10-01

Reports of molecular and cellular imaging using computed tomography (CT) are rapidly increasing. Many of these reports use gold nanoparticles. Bismuth has similar CT contrast properties to gold while being approximately 1000-fold less expensive. Herein we report the design, fabrication, characterization, and CT and fluorescence imaging properties of a novel, dual modality, fluorescent, polymer encapsulated bismuth nanoparticle construct for computed tomography and fluorescence imaging. We also report on cellular internalization and preliminary in vitro and in vivo toxicity effects of these constructs. 40 nm bismuth(0) nanocrystals were synthesized and encapsulated within 120 nm Poly(dl-lactic-co-glycolic acid) (PLGA) nanoparticles by oil-in-water emulsion methodologies. Coumarin-6 was co-encapsulated to impart fluorescence. High encapsulation efficiency was achieved ~70% bismuth w/w. Particles were shown to internalize within cells following incubation in culture. Bismuth nanocrystals and PLGA encapsulated bismuth nanoparticles exhibited >90% and >70% degradation, respectively, within 24 hours in acidic, lysosomal environment mimicking media and both remained nearly 100% stable in cytosolic/extracellular fluid mimicking media. μCT and clinical CT imaging was performed at multiple X-ray tube voltages to measure concentration dependent attenuation rates as well as to establish the ability to detect the nanoparticles in an ex vivo biological sample. Dual fluorescence and CT imaging is demonstrated as well. In vivo toxicity studies in rats revealed neither clinically apparent side effects nor major alterations in serum chemistry and hematology parameters. Calculations on minimal detection requirements for in vivo targeted imaging using these nanoparticles are presented. Indeed, our results indicate that these nanoparticles may serve as a platform for sensitive and specific targeted molecular CT and fluorescence imaging.Reports of molecular and cellular imaging using computed tomography (CT) are rapidly increasing. Many of these reports use gold nanoparticles. Bismuth has similar CT contrast properties to gold while being approximately 1000-fold less expensive. Herein we report the design, fabrication, characterization, and CT and fluorescence imaging properties of a novel, dual modality, fluorescent, polymer encapsulated bismuth nanoparticle construct for computed tomography and fluorescence imaging. We also report on cellular internalization and preliminary in vitro and in vivo toxicity effects of these constructs. 40 nm bismuth(0) nanocrystals were synthesized and encapsulated within 120 nm Poly(dl-lactic-co-glycolic acid) (PLGA) nanoparticles by oil-in-water emulsion methodologies. Coumarin-6 was co-encapsulated to impart fluorescence. High encapsulation efficiency was achieved ~70% bismuth w/w. Particles were shown to internalize within cells following incubation in culture. Bismuth nanocrystals and PLGA encapsulated bismuth nanoparticles exhibited >90% and >70% degradation, respectively, within 24 hours in acidic, lysosomal environment mimicking media and both remained nearly 100% stable in cytosolic/extracellular fluid mimicking media. μCT and clinical CT imaging was performed at multiple X-ray tube voltages to measure concentration dependent attenuation rates as well as to establish the ability to detect the nanoparticles in an ex vivo biological sample. Dual fluorescence and CT imaging is demonstrated as well. In vivo toxicity studies in rats revealed neither clinically apparent side effects nor major alterations in serum chemistry and hematology parameters. Calculations on minimal detection requirements for in vivo targeted imaging using these nanoparticles are presented. Indeed, our results indicate that these nanoparticles may serve as a platform for sensitive and specific targeted molecular CT and fluorescence imaging. Electronic supplementary information (ESI) available. See DOI: 10.1039/c4nr01405g

Hybrid imaging: Instrumentation and Data Processing

NASA Astrophysics Data System (ADS)

Cal-Gonzalez, Jacobo; Rausch, Ivo; Shiyam Sundar, Lalith K.; Lassen, Martin L.; Muzik, Otto; Moser, Ewald; Papp, Laszlo; Beyer, Thomas

2018-05-01

State-of-the-art patient management frequently requires the use of non-invasive imaging methods to assess the anatomy, function or molecular-biological conditions of patients or study subjects. Such imaging methods can be singular, providing either anatomical or molecular information, or they can be combined, thus, providing "anato-metabolic" information. Hybrid imaging denotes image acquisitions on systems that physically combine complementary imaging modalities for an improved diagnostic accuracy and confidence as well as for increased patient comfort. The physical combination of formerly independent imaging modalities was driven by leading innovators in the field of clinical research and benefited from technological advances that permitted the operation of PET and MR in close physical proximity, for example. This review covers milestones of the development of various hybrid imaging systems for use in clinical practice and small-animal research. Special attention is given to technological advances that helped the adoption of hybrid imaging, as well as to introducing methodological concepts that benefit from the availability of complementary anatomical and biological information, such as new types of image reconstruction and data correction schemes. The ultimate goal of hybrid imaging is to provide useful, complementary and quantitative information during patient work-up. Hybrid imaging also opens the door to multi-parametric assessment of diseases, which will help us better understand the causes of various diseases that currently contribute to a large fraction of healthcare costs.

Method and apparatus to image biological interactions in plants

DOEpatents

Weisenberger, Andrew; Bonito, Gregory M.; Reid, Chantal D.; Smith, Mark Frederick

2015-12-22

A method to dynamically image the actual translocation of molecular compounds of interest in a plant root, root system, and rhizosphere without disturbing the root or the soil. The technique makes use of radioactive isotopes as tracers to label molecules of interest and to image their distribution in the plant and/or soil. The method allows for the study and imaging of various biological and biochemical interactions in the rhizosphere of a plant, including, but not limited to, mycorrhizal associations in such regions.

Simulated structure and imaging of NTCDI on Si(1 1 1)-7 × 7 : a combined STM, NC-AFM and DFT study

NASA Astrophysics Data System (ADS)

Jarvis, S. P.; Sweetman, A. M.; Lekkas, I.; Champness, N. R.; Kantorovich, L.; Moriarty, P.

2015-02-01

The adsorption of naphthalene tetracarboxylic diimide (NTCDI) on Si(1 1 1)-7 × 7 is investigated through a combination of scanning tunnelling microscopy (STM), noncontact atomic force microscopy (NC-AFM) and density functional theory (DFT) calculations. We show that NTCDI adopts multiple planar adsorption geometries on the Si(1 1 1)-7 × 7 surface which can be imaged with intramolecular bond resolution using NC-AFM. DFT calculations reveal adsorption is dominated by covalent bond formation between the molecular oxygen atoms and the surface silicon adatoms. The chemisorption of the molecule is found to induce subtle distortions to the molecular structure, which are observed in NC-AFM images.

Functionalized Gold Nanorods for Tumor Imaging and Targeted Therapy

PubMed Central

Gui, Chen; Cui, Da-xiang

2012-01-01

Gold nanorods, as an emerging noble metal nanomaterial with unique properties, have become the new exciting focus of theoretical and experimental studies in the past few years. The structure and function of gold nanorods, especially their biocompatibility, optical property, and photothermal effects, have been attracting more and more attention. Gold nanorods exhibit great potential in applications such as tumor molecular imaging and photothermal therapy. In this article, we review some of the main advances made over the past few years in the application of gold nanorods in surface functionalization, molecular imaging, and photothermal therapy. We also explore other prospective applications and discuss the corresponding concepts, issues, approaches, and challenges, with the aim of stimulating broader interest in gold nanorod-based nanotechnology and improving its practical application. PMID:23691482

Silver Coating for High-Mass-Accuracy Imaging Mass Spectrometry of Fingerprints on Nanostructured Silicon.

PubMed

Guinan, Taryn M; Gustafsson, Ove J R; McPhee, Gordon; Kobus, Hilton; Voelcker, Nicolas H

2015-11-17

Nanostructure imaging mass spectrometry (NIMS) using porous silicon (pSi) is a key technique for molecular imaging of exogenous and endogenous low molecular weight compounds from fingerprints. However, high-mass-accuracy NIMS can be difficult to achieve as time-of-flight (ToF) mass analyzers, which dominate the field, cannot sufficiently compensate for shifts in measured m/z values. Here, we show internal recalibration using a thin layer of silver (Ag) sputter-coated onto functionalized pSi substrates. NIMS peaks for several previously reported fingerprint components were selected and mass accuracy was compared to theoretical values. Mass accuracy was improved by more than an order of magnitude in several cases. This straightforward method should form part of the standard guidelines for NIMS studies for spatial characterization of small molecules.

Preclinical Magnetic Resonance Imaging and Spectroscopy Studies of Memory, Aging, and Cognitive Decline

PubMed Central

Febo, Marcelo; Foster, Thomas C.

2016-01-01

Neuroimaging provides for non-invasive evaluation of brain structure and activity and has been employed to suggest possible mechanisms for cognitive aging in humans. However, these imaging procedures have limits in terms of defining cellular and molecular mechanisms. In contrast, investigations of cognitive aging in animal models have mostly utilized techniques that have offered insight on synaptic, cellular, genetic, and epigenetic mechanisms affecting memory. Studies employing magnetic resonance imaging and spectroscopy (MRI and MRS, respectively) in animal models have emerged as an integrative set of techniques bridging localized cellular/molecular phenomenon and broader in vivo neural network alterations. MRI methods are remarkably suited to longitudinal tracking of cognitive function over extended periods permitting examination of the trajectory of structural or activity related changes. Combined with molecular and electrophysiological tools to selectively drive activity within specific brain regions, recent studies have begun to unlock the meaning of fMRI signals in terms of the role of neural plasticity and types of neural activity that generate the signals. The techniques provide a unique opportunity to causally determine how memory-relevant synaptic activity is processed and how memories may be distributed or reconsolidated over time. The present review summarizes research employing animal MRI and MRS in the study of brain function, structure, and biochemistry, with a particular focus on age-related cognitive decline. PMID:27468264

Molecular imaging of rheumatoid arthritis: emerging markers, tools, and techniques

PubMed Central

2014-01-01

Early diagnosis and effective monitoring of rheumatoid arthritis (RA) are important for a positive outcome. Instant treatment often results in faster reduction of inflammation and, as a consequence, less structural damage. Anatomical imaging techniques have been in use for a long time, facilitating diagnosis and monitoring of RA. However, mere imaging of anatomical structures provides little information on the processes preceding changes in synovial tissue, cartilage, and bone. Molecular imaging might facilitate more effective diagnosis and monitoring in addition to providing new information on the disease pathogenesis. A limiting factor in the development of new molecular imaging techniques is the availability of suitable probes. Here, we review which cells and molecules can be targeted in the RA joint and discuss the advances that have been made in imaging of arthritis with a focus on such molecular targets as folate receptor, F4/80, macrophage mannose receptor, E-selectin, intercellular adhesion molecule-1, phosphatidylserine, and matrix metalloproteinases. In addition, we discuss a new tool that is being introduced in the field, namely the use of nanobodies as tracers. Finally, we describe additional molecules displaying specific features in joint inflammation and propose these as potential new molecular imaging targets, more specifically receptor activator of nuclear factor κB and its ligand, chemokine receptors, vascular cell adhesion molecule-1, αVβ3 integrin, P2X7 receptor, suppression of tumorigenicity 2, dendritic cell-specific transmembrane protein, and osteoclast-stimulatory transmembrane protein. PMID:25099015

Molecular imaging-guided photothermal/photodynamic therapy against tumor by iRGD-modified indocyanine green nanoparticles.

PubMed

Yan, Fei; Wu, Hao; Liu, Hongmei; Deng, Zhiting; Liu, Hong; Duan, Wanlu; Liu, Xin; Zheng, Hairong

2016-02-28

Multifunctional near-infrared (NIR) nanoparticles demonstrate great potential in tumor theranostic applications. To achieve the sensitive detection and effective phototherapy in the early stage of tumor genesis, it is highly desirable to improve the targeting of NIR theranostic agents to biomarkers and to enhance their accumulation in tumor. Here we report a novel targeted multifunctional theranostic nanoparticle, internalized RGD (iRGD)-modified indocyanine green (ICG) liposomes (iRGD-ICG-LPs), for molecular imaging-guided photothermal therapy (PTT) and photodynamic therapy (PDT) therapy against breast tumor. The iRGD peptides with high affinity to αvβ3 integrin and effective tumor-internalized property were firstly used to synthesize iRGD-PEG2000-DSPE lipopeptides, which were further utilized to fabricate the targeted ICG liposomes. The results indicated that iRGD-ICG-LPs exhibited excellent stability and could provide an accurate and sensitive detection of breast tumor through NIR fluorescence molecular imaging. We further employed this nanoparticle for tumor theranostic application, demonstrating significantly higher tumor accumulation and tumor inhibition efficacy through PTT/PDT effects. Histological analysis further revealed much more apoptotic cells, confirming the advantageous anti-tumor effect of iRGD-ICG-LPs over non-targeted ICG-LPs. Notably, the targeting therapy mediated by iRGD provides almost equivalent anti-tumor efficacy at a 12.5-fold lower drug dose than that by monoclonal antibody, and no tumor recurrence and obvious treatment-induced toxicity were observed in our study. Our study provides a promising strategy to realize the sensitive detection and effective treatment of tumors by integrating molecular imaging into PTT/PDT therapy. Copyright © 2015. Published by Elsevier B.V.

Quantum dot-based molecular imaging of cancer cell growth using a clone formation assay.

PubMed

Geng, Xia-Fei; Fang, Min; Liu, Shao-Ping; Li, Yan

2016-10-01

This aim of the present study was to investigate clonal growth behavior and analyze the proliferation characteristics of cancer cells. The MCF‑7 human breast cancer cell line, SW480 human colon cancer cell line and SGC7901 human gastric cancer cell line were selected to investigate the morphology of cell clones. Quantum dot‑based molecular targeted imaging techniques (which stained pan‑cytokeratin in the cytoplasm green and Ki67 in the cell nucleus yellow or red) were used to investigate the clone formation rate, cell morphology, discrete tendency, and Ki67 expression and distribution in clones. From the cell clone formation assay, the MCF‑7, SW480 and SGC7901 cells were observed to form clones on days 6, 8 and 12 of cell culture, respectively. These three types of cells had heterogeneous morphology, large nuclear:cytoplasmic ratios, and conspicuous pathological mitotic features. The cells at the clone periphery formed multiple pseudopodium. In certain clones, cancer cells at the borderline were separated from the central cell clusters or presented a discrete tendency. With quantum dot‑based molecular targeted imaging techniques, cells with strong Ki67 expression were predominantly shown to be distributed at the clone periphery, or concentrated on one side of the clones. In conclusion, cancer cell clones showed asymmetric growth behavior, and Ki67 was widely expressed in clones of these three cell lines, with strong expression around the clones, or aggregated at one side. Cell clone formation assay based on quantum dots molecular imaging offered a novel method to study the proliferative features of cancer cells, thus providing a further insight into tumor biology.

Biomolecular Imaging with Coherent Nonlinear Vibrational Microscopy

PubMed Central

Chung, Chao-Yu; Boik, John; Potma, Eric O.

2014-01-01

Optical imaging with spectroscopic vibrational contrast is a label-free solution for visualizing, identifying, and quantifying a wide range of biomolecular compounds in biological materials. Both linear and nonlinear vibrational microscopy techniques derive their imaging contrast from infrared active or Raman allowed molecular transitions, which provide a rich palette for interrogating chemical and structural details of the sample. Yet nonlinear optical methods, which include both second-order sum-frequency generation (SFG) and third-order coherent Raman scattering (CRS) techniques, offer several improved imaging capabilities over their linear precursors. Nonlinear vibrational microscopy features unprecedented vibrational imaging speeds, provides strategies for higher spatial resolution, and gives access to additional molecular parameters. These advances have turned vibrational microscopy into a premier tool for chemically dissecting live cells and tissues. This review discusses the molecular contrast of SFG and CRS microscopy and highlights several of the advanced imaging capabilities that have impacted biological and biomedical research. PMID:23245525

Probing amyloid protein aggregation with optical superresolution methods: from the test tube to models of disease

PubMed Central

Kaminski, Clemens F.; Kaminski Schierle, Gabriele S.

2016-01-01

Abstract. The misfolding and self-assembly of intrinsically disordered proteins into insoluble amyloid structures are central to many neurodegenerative diseases such as Alzheimer’s and Parkinson’s diseases. Optical imaging of this self-assembly process in vitro and in cells is revolutionizing our understanding of the molecular mechanisms behind these devastating conditions. In contrast to conventional biophysical methods, optical imaging and, in particular, optical superresolution imaging, permits the dynamic investigation of the molecular self-assembly process in vitro and in cells, at molecular-level resolution. In this article, current state-of-the-art imaging methods are reviewed and discussed in the context of research into neurodegeneration. PMID:27413767

Depth-resolved imaging of colon tumor using optical coherence tomography and fluorescence laminar optical tomography (Conference Presentation)

NASA Astrophysics Data System (ADS)

Tang, Qinggong; Frank, Aaron; Wang, Jianting; Chen, Chao-wei; Jin, Lily; Lin, Jon; Chan, Joanne M.; Chen, Yu

2016-03-01

Early detection of neoplastic changes remains a critical challenge in clinical cancer diagnosis and treatment. Many cancers arise from epithelial layers such as those of the gastrointestinal (GI) tract. Current standard endoscopic technology is unable to detect those subsurface lesions. Since cancer development is associated with both morphological and molecular alterations, imaging technologies that can quantitative image tissue's morphological and molecular biomarkers and assess the depth extent of a lesion in real time, without the need for tissue excision, would be a major advance in GI cancer diagnostics and therapy. In this research, we investigated the feasibility of multi-modal optical imaging including high-resolution optical coherence tomography (OCT) and depth-resolved high-sensitivity fluorescence laminar optical tomography (FLOT) for structural and molecular imaging. APC (adenomatous polyposis coli) mice model were imaged using OCT and FLOT and the correlated histopathological diagnosis was obtained. Quantitative structural (the scattering coefficient) and molecular imaging parameters (fluorescence intensity) from OCT and FLOT images were developed for multi-parametric analysis. This multi-modal imaging method has demonstrated the feasibility for more accurate diagnosis with 87.4% (87.3%) for sensitivity (specificity) which gives the most optimal diagnosis (the largest area under receiver operating characteristic (ROC) curve). This project results in a new non-invasive multi-modal imaging platform for improved GI cancer detection, which is expected to have a major impact on detection, diagnosis, and characterization of GI cancers, as well as a wide range of epithelial cancers.

Defocused Imaging of UV-Driven Surface-Bound Molecular Motors.

PubMed

Krajnik, Bartosz; Chen, Jiawen; Watson, Matthew A; Cockroft, Scott L; Feringa, Ben L; Hofkens, Johan

2017-05-31

Synthetic molecular motors continue to attract great interest due to their ability to transduce energy into nanomechanical motion, the potential to do work and drive systems out-of-equilibrium. Of particular interest are unidirectional rotary molecular motors driven by chemical fuel or light. Probing the mechanistic details of their operation at the single-molecule level is hampered by the diffraction limit, which prevents the collection of dynamic positional information by traditional optical methods. Here, we use defocused wide-field imaging to examine the unidirectional rotation of individual molecular rotary motors on a quartz surface in unprecedented detail. The sequential occupation of nanomechanical states during the UV and heat-induced cycle of rotation are directly imaged in real-time. The approach will undoubtedly prove important in elucidating the mechanistic details and assessing the utility of novel synthetic molecular motors in the future.

Advances in molecular imaging for breast cancer detection and characterization

PubMed Central

2012-01-01

Advances in our ability to assay molecular processes, including gene expression, protein expression, and molecular and cellular biochemistry, have fueled advances in our understanding of breast cancer biology and have led to the identification of new treatments for patients with breast cancer. The ability to measure biologic processes without perturbing them in vivo allows the opportunity to better characterize tumor biology and to assess how biologic and cytotoxic therapies alter critical pathways of tumor response and resistance. By accurately characterizing tumor properties and biologic processes, molecular imaging plays an increasing role in breast cancer science, clinical care in diagnosis and staging, assessment of therapeutic targets, and evaluation of responses to therapies. This review describes the current role and potential of molecular imaging modalities for detection and characterization of breast cancer and focuses primarily on radionuclide-based methods. PMID:22423895

Radiolabeled Nanoparticles for Multimodality Tumor Imaging

PubMed Central

Xing, Yan; Zhao, Jinhua; Conti, Peter S.; Chen, Kai

2014-01-01

Each imaging modality has its own unique strengths. Multimodality imaging, taking advantages of strengths from two or more imaging modalities, can provide overall structural, functional, and molecular information, offering the prospect of improved diagnostic and therapeutic monitoring abilities. The devices of molecular imaging with multimodality and multifunction are of great value for cancer diagnosis and treatment, and greatly accelerate the development of radionuclide-based multimodal molecular imaging. Radiolabeled nanoparticles bearing intrinsic properties have gained great interest in multimodality tumor imaging over the past decade. Significant breakthrough has been made toward the development of various radiolabeled nanoparticles, which can be used as novel cancer diagnostic tools in multimodality imaging systems. It is expected that quantitative multimodality imaging with multifunctional radiolabeled nanoparticles will afford accurate and precise assessment of biological signatures in cancer in a real-time manner and thus, pave the path towards personalized cancer medicine. This review addresses advantages and challenges in developing multimodality imaging probes by using different types of nanoparticles, and summarizes the recent advances in the applications of radiolabeled nanoparticles for multimodal imaging of tumor. The key issues involved in the translation of radiolabeled nanoparticles to the clinic are also discussed. PMID:24505237

High-Performance Computational Analysis of Glioblastoma Pathology Images with Database Support Identifies Molecular and Survival Correlates.

PubMed

Kong, Jun; Wang, Fusheng; Teodoro, George; Cooper, Lee; Moreno, Carlos S; Kurc, Tahsin; Pan, Tony; Saltz, Joel; Brat, Daniel

2013-12-01

In this paper, we present a novel framework for microscopic image analysis of nuclei, data management, and high performance computation to support translational research involving nuclear morphometry features, molecular data, and clinical outcomes. Our image analysis pipeline consists of nuclei segmentation and feature computation facilitated by high performance computing with coordinated execution in multi-core CPUs and Graphical Processor Units (GPUs). All data derived from image analysis are managed in a spatial relational database supporting highly efficient scientific queries. We applied our image analysis workflow to 159 glioblastomas (GBM) from The Cancer Genome Atlas dataset. With integrative studies, we found statistics of four specific nuclear features were significantly associated with patient survival. Additionally, we correlated nuclear features with molecular data and found interesting results that support pathologic domain knowledge. We found that Proneural subtype GBMs had the smallest mean of nuclear Eccentricity and the largest mean of nuclear Extent, and MinorAxisLength. We also found gene expressions of stem cell marker MYC and cell proliferation maker MKI67 were correlated with nuclear features. To complement and inform pathologists of relevant diagnostic features, we queried the most representative nuclear instances from each patient population based on genetic and transcriptional classes. Our results demonstrate that specific nuclear features carry prognostic significance and associations with transcriptional and genetic classes, highlighting the potential of high throughput pathology image analysis as a complementary approach to human-based review and translational research.

Current Perspectives in Imaging Modalities for the Assessment of Unruptured Intracranial Aneurysms: A Comparative Analysis and Review.

PubMed

Turan, Nefize; Heider, Robert A; Roy, Anil K; Miller, Brandon A; Mullins, Mark E; Barrow, Daniel L; Grossberg, Jonathan; Pradilla, Gustavo

2018-05-01

Intracranial aneurysms (IAs) are pathologic dilatations of cerebral arteries. This systematic review summarizes and compares imaging techniques for assessing unruptured IAs (UIAs). This review also addresses their uses in different scopes of practice. Pathophysiologic mechanisms are reviewed to better understand the clinical usefulness of each imaging modality. A literature review was performed using PubMed with these search terms: "intracranial aneurysm," "cerebral aneurysm," "magnetic resonance angiography (MRA)," computed tomography angiography (CTA)," "catheter angiography," "digital subtraction angiography," "molecular imaging," "ferumoxytol," and "myeloperoxidase". Only studies in English were cited. Since the development and improvement of noninvasive diagnostic imaging (computed tomography angiography and magnetic resonance angiography), many prospective studies and meta-analyses have compared these tests with gold standard digital subtraction angiography (DSA). Although computed tomography angiography and magnetic resonance angiography have lower detection rates for UIAs, they are vital in the treatment and follow-up of UIAs. The reduction in ionizing radiation and lack of endovascular instrumentation with these modalities provide benefits compared with DSA. Novel molecular imaging techniques to detect inflammation within the aneurysmal wall with the goal of stratifying risk based on level of inflammation are under investigation. DSA remains the gold standard for preoperative planning and follow-up for patients with IA. Newer imaging modalities such as ferumoxytol-enhanced magnetic resonance imaging are emerging techniques that provide critical in vivo information about the inflammatory milieu within aneurysm walls. With further study, these techniques may provide aneurysm rupture risk and prediction models for individualized patient care. Copyright © 2018 Elsevier Inc. All rights reserved.

Combined Magnetic Resonance Imaging and Spectroscopic Imaging Approach to Molecular Imaging of Prostate Cancer

PubMed Central

Kurhanewicz, John; Swanson, Mark G.; Nelson, Sarah J.; Vigneron, Daniel B.

2005-01-01

Magnetic resonance spectroscopic imaging (MRSI) provides a noninvasive method of detecting small molecular markers (historically the metabolites choline and citrate) within the cytosol and extracellular spaces of the prostate, and is performed in conjunction with high-resolution anatomic imaging. Recent studies in pre-prostatectomy patients have indicated that the metabolic information provided by MRSI combined with the anatomical information provided by MRI can significantly improve the assessment of cancer location and extent within the prostate, extracapsular spread, and cancer aggressiveness. Additionally, pre- and post-therapy studies have demonstrated the potential of MRI/MRSI to provide a direct measure of the presence and spatial extent of prostate cancer after therapy, a measure of the time course of response, and information concerning the mechanism of therapeutic response. In addition to detecting metabolic biomarkers of disease behavior and therapeutic response, MRI/MRSI guidance can improve tissue selection for ex vivo analysis. High-resolution magic angle spinning (1H HR-MAS) spectroscopy provides a full chemical analysis of MRI/MRSI-targeted tissues prior to pathologic and immunohistochemical analyses of the same tissue. Preliminary 1H HR-MAS spectroscopy studies have already identified unique spectral patterns for healthy glandular and stromal tissues and prostate cancer, determined the composition of the composite in vivo choline peak, and identified the polyamine spermine as a new metabolic marker of prostate cancer. The addition of imaging sequences that provide other functional information within the same exam (dynamic contrast uptake imaging and diffusion-weighted imaging) have also demonstrated the potential to further increase the accuracy of prostate cancer detection and characterization. PMID:12353259

Molecular Imaging of the Kidneys

PubMed Central

Szabo, Zsolt; Alachkar, Nada; Xia, Jinsong; Mathews, William B.; Rabb, Hamid

2010-01-01

Radionuclide imaging of the kidneys with gamma cameras involves the use of labeled molecules seeking functionally critical molecular mechanisms in order to detect the pathophysiology of the diseased kidneys and achieve an early, sensitive and accurate diagnosis. The most recent imaging technology, PET, permits quantitative imaging of the kidney at a spatial resolution appropriate for the organ. H215O, 82RbCl, and [64Cu] ETS are the most important radiopharmaceuticals for measuring renal blood flow. The renin angiotensin system is the most important regulator of renal blood flow; this role is being interrogated by detecting angiotensin receptor subtype AT1R using in vivo PET imaging. Membrane organic anion transporters are important for the function of the tubular epithelium; therefore, Tc-99m MAG3 as well as some novel radiopharmaceuticals such as copper-64 labeled mono oxo-tetraazamacrocyclic ligands have been utilized for molecular renal imaging. Additionally, other radioligands that interact with the organic cation transporters or peptide transporters have developed. Focusing on early detection of kidney injury at the molecular level is an evolving field of great significance. Potential imaging targets are the kidney injury molecule- 1 (KIM-1) that is highly expressed in kidney injury and renal cancer but not in normal kidneys. While pelvic clearance, in addition to parenchymal transport, is an important measure in obstructive nephropathy, techniques that focus on upregulated molecules in response to tissue stress resulted from obstruction will be of great implication. Monocyte chemoattractant protein -1 (MCP-1) is a well-suited molecule in this case. The greatest advances in molecular imaging of the kidneys have been recently achieved in detecting renal cancer. In addition to the ubiquitous [18F]FDG, other radioligands such as [11C]acetate and anti-[18F]FACBC have emerged. Radioimmuno-imaging with [124I]G250 could lead to radioimmunotherapy for renal cancer. Considering the increasing age of general population, the incidence of kidney diseases such as atherosclerosis, diabetic nephropathy, and cancer is expected to increase. Successful management of these diseases offers an opportunity and a challenge for development of novel molecular imaging technologies. PMID:21111857

Molecular imaging in drug development: Update and challenges for radiolabeled antibodies and nanotechnology.

PubMed

Colombo, Ilaria; Overchuk, Marta; Chen, Juan; Reilly, Raymond M; Zheng, Gang; Lheureux, Stephanie

2017-11-01

Despite the significant advancement achieved in understanding the molecular mechanisms responsible for cancer transformation and aberrant proliferation, leading to novel targeted cancer therapies, significant effort is still needed to "personalize" cancer treatment. Molecular imaging is an emerging field that has shown the ability to characterize in vivo the molecular pathways present at the cancer cell level, enabling diagnosis and personalized treatment of malignancies. These technologies, particularly SPECT and PET also permit the development of novel radiotheranostic probes, which provide capabilities for diagnosis and treatment with the same agent. The small therapeutic index of most anticancer agents is a limitation in the drug development process. Incorporation of molecular imaging in clinical research may help in overcoming this limitation and favouring selection of patient populations most likely to achieve benefit from targeted therapy. This review will focus on two of the most advanced theranostic approaches with promising potential for application in the clinic: 1) therapeutic monoclonal antibodies which may be linked to a radionuclide for SPECT or PET imaging to guide cancer diagnosis, staging, molecular characterization, and assessment of the response to treatment and 2) multifunctional nanotechnology that allows image guided drug delivery through encapsulation of multiple therapeutic, targeting and imaging agents into a single nanoparticle. Porphysome, a liposome-like nanoparticle, is an example of a novel and promising application of nanotechnology for cancer diagnosis and treatment. These technologies have proven to be effective in preclinical models, warranting further clinical investigation to advance their application for the benefit of cancer patients. Copyright © 2017 Elsevier Inc. All rights reserved.

Molecular imaging in the diagnosis of Alzheimer's disease and related disorders.

PubMed

Koric, L; Guedj, E; Habert, M O; Semah, F; Branger, P; Payoux, P; Le Jeune, F

2016-12-01

The diagnosis of Alzheimer's disease (AD) and its related disorders rely on clinical criteria. There is, however, a large clinical overlap between the different neurodegenerative diseases affecting cognition and, frequently, there are diagnostic uncertainties with atypical clinical presentations. Current clinical practices can now regularly use positron emission tomography (PET) and single-photon emission computed tomography (SPECT) molecular imaging to help resolve such uncertainties. The Neurology Group of the French Society of Nuclear Medicine and Federations of Memory, Resources and Research Centers have collaborated to establish clinical guidelines to determine which molecular imaging techniques to use when seeking a differential diagnosis between AD and other neurodegenerative disorders affecting cognition. According to the current medical literature, the potential usefulness of molecular imaging to address the typical clinical criteria in common forms of AD remains modest, as typical AD presentations rarely raise questions of differential diagnoses with other neurodegenerative disorders. However, molecular imaging could be of significant value in the diagnosis of atypical neurodegenerative disorders, including early onset, rapid cognitive decline, prominent non-amnestic presentations involving language, visuospatial, behavioral/executive and/or non-cognitive symptoms in AD, or prominent amnestic presentations in other non-AD dementias. The clinical use of molecular imaging should be recommended for assessing cognitive disturbances particularly in patients with early clinical onset (before age 65) and atypical presentations. However, diagnostic tools should always be part of the global clinical approach, as an isolated positive result cannot adequately establish a diagnosis of any neurodegenerative disorder. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

[Redox Molecular Imaging Using ReMI].

PubMed

Hyodo, Fuminori; Ito, Shinji; Utsumi, Hideo

2015-01-01

Tissue redox status is one of the most important parameters to maintain homeostasis in the living body. Numerous redox reactions are involved in metabolic processes, such as energy production in the mitochondrial electron transfer system. A variety of intracellular molecules such as reactive oxygen species, glutathione, thioredoxins, NADPH, flavins, and ascorbic acid may contribute to the overall redox status in tissues. Breakdown of redox balance may lead to oxidative stress and can induce many pathological conditions such as cancer, neurological disorders, and aging. Therefore imaging of tissue redox status and monitoring antioxidant levels in living organisms can be useful in the diagnosis of disease states and assessment of treatment response. In vivo redox molecular imaging technology such as electron spin resonance imaging (ESRI), magnetic resonance imaging (MRI), and dynamic nuclear polarization (DNP)-MRI (redox molecular imaging; ReMI) is emerging as a viable redox status imaging modality. This review focuses on the application of magnetic resonance technologies using MRI or DNP-MRI and redox-sensitive contrast agents.

Development of ultrasound bioprobe for biological imaging

PubMed Central

Shekhawat, Gajendra S.; Dudek, Steven M.; Dravid, Vinayak P.

2017-01-01

We report the development of an ultrasound bioprobe for in vitro molecular imaging. In this method, the phase of the scattered ultrasound wave is mapped to provide in vitro and intracellular imaging with nanometer-scale resolution under physiological conditions. We demonstrated the technique by successfully imaging a magnetic core in silica core shells and the stiffness image of intracellular fibers in endothelial cells that were stimulated with thrombin. The findings demonstrate a significant advancement in high-resolution ultrasound imaging of biological systems with acoustics under physiological conditions. These will open up various applications in biomedical and molecular imaging with subsurface resolution down to the nanometer scale. PMID:29075667

Factors associated with success of image-guided tumour biopsies: Results from a prospective molecular triage study (MOSCATO-01).

PubMed

Tacher, Vania; Le Deley, Marie-Cécile; Hollebecque, Antoine; Deschamps, Frederic; Vielh, Philippe; Hakime, Antoine; Ileana, Ecaterina; Abedi-Ardekani, Behnoush; Charpy, Cécile; Massard, Christophe; Rosellini, Silvia; Gajda, Dorota; Celebic, Aljosa; Ferté, Charles; Ngo-Camus, Maud; Gouissem, Siham; Koubi-Pick, Valérie; Andre, Fabrice; Vassal, Gilles; Deandreis, Désirée; Lacroix, Ludovic; Soria, Jean-Charles; De Baère, Thierry

2016-05-01

MOSCATO-01 is a molecular triage trial based on on-purpose tumour biopsies to perform molecular portraits. We aimed at identifying factors associated with high tumour cellularity. Tumour cellularity (percentage of tumour cells in samples defined at pathology) was evaluated according to patient characteristics, target lesion characteristics, operators' experience and biopsy approach. Among 460 patients enrolled between November, 2011 and March, 2014, 334 patients (73%) had an image-guided needle biopsy of the primary tumour (N = 38) or a metastatic lesion (N = 296). Biopsies were performed on liver (N = 127), lung (N = 72), lymph nodes (N = 71), bone (N = 11), or another tumour site (N = 53). Eighteen patients (5%) experienced a complication: pneumothorax in 10 patients treated medically, and haemorrhage in 8, requiring embolisation in 3 cases. Median tumour cellularity was 50% (interquartile range, 30-70%). The molecular analysis was successful in 291/334 cases (87%). On-going chemotherapy, tumour origin (primary versus metastatic), lesion size, tumour growth rate, presence of necrosis on imaging, standardised uptake value, and needle size were not statistically associated with cellularity. Compared to liver or lung biopsies, cellularity was significantly lower in bone and higher in other sites (P < 0.0001). Cellularity significantly increased with the number of collected samples (P < 0.0001) and was higher in contrast-enhanced ultrasound-guided biopsies (P < 0.02). In paired samples, cellularity in central samples was lower than in peripheral samples in 85, equal in 68 and higher in 89 of the cases. Image-guided biopsy is feasible and safe in cancer patients for molecular screening. Imaging modality, multiple sampling of the lesion, and the organ chosen for biopsy were associated with higher tumour cellularity. Copyright © 2016 Elsevier Ltd. All rights reserved.

Dual-modality, fluorescent, PLGA encapsulated bismuth nanoparticles for molecular and cellular fluorescence imaging and computed tomography.

PubMed

Swy, Eric R; Schwartz-Duval, Aaron S; Shuboni, Dorela D; Latourette, Matthew T; Mallet, Christiane L; Parys, Maciej; Cormode, David P; Shapiro, Erik M

2014-11-07

Reports of molecular and cellular imaging using computed tomography (CT) are rapidly increasing. Many of these reports use gold nanoparticles. Bismuth has similar CT contrast properties to gold while being approximately 1000-fold less expensive. Herein we report the design, fabrication, characterization, and CT and fluorescence imaging properties of a novel, dual modality, fluorescent, polymer encapsulated bismuth nanoparticle construct for computed tomography and fluorescence imaging. We also report on cellular internalization and preliminary in vitro and in vivo toxicity effects of these constructs. 40 nm bismuth(0) nanocrystals were synthesized and encapsulated within 120 nm Poly(dl-lactic-co-glycolic acid) (PLGA) nanoparticles by oil-in-water emulsion methodologies. Coumarin-6 was co-encapsulated to impart fluorescence. High encapsulation efficiency was achieved ∼70% bismuth w/w. Particles were shown to internalize within cells following incubation in culture. Bismuth nanocrystals and PLGA encapsulated bismuth nanoparticles exhibited >90% and >70% degradation, respectively, within 24 hours in acidic, lysosomal environment mimicking media and both remained nearly 100% stable in cytosolic/extracellular fluid mimicking media. μCT and clinical CT imaging was performed at multiple X-ray tube voltages to measure concentration dependent attenuation rates as well as to establish the ability to detect the nanoparticles in an ex vivo biological sample. Dual fluorescence and CT imaging is demonstrated as well. In vivo toxicity studies in rats revealed neither clinically apparent side effects nor major alterations in serum chemistry and hematology parameters. Calculations on minimal detection requirements for in vivo targeted imaging using these nanoparticles are presented. Indeed, our results indicate that these nanoparticles may serve as a platform for sensitive and specific targeted molecular CT and fluorescence imaging.

Animal models for the study of inflammatory bowel diseases: a meta-analysis on modalities for imaging inflammatory lesions.

PubMed

Auletta, Sveva; Bonfiglio, Rita; Wunder, Andreas; Varani, Michela; Galli, Filippo; Borri, Filippo; Scimeca, Manuel; Niessen, Heiko G; Schönberger, Tanja; Bonanno, Elena

2018-03-01

Inflammatory bowel diseases are lifelong disorders affecting the gastrointestinal tract characterized by intermittent disease flares and periods of remission with a progressive and destructive nature. Unfortunately, the exact etiology is still not completely known, therefore a causal therapy to cure the disease is not yet available. Current treatment options mainly encompass the use of non-specific anti-inflammatory agents and immunosuppressive drugs that cause significant side effects that often have a negative impact on patients' quality of life. As the majority of patients need a long-term follow-up it would be ideal to rely on a non-invasive technique with good compliance. Currently, the gold standard diagnostic tools for managing IBD are represented by invasive procedures such as colonoscopy and histopathology. Nevertheless, recent advances in imaging technology continue to improve the ability of imaging techniques to non-invasively monitor disease activity and treatment response in preclinical models of IBD. Novel and emerging imaging techniques not only allow direct visualization of intestinal inflammation, but also enable molecular imaging and targeting of specific alterations of the inflamed murine mucosa. Furthermore, molecular imaging advances allow us to increase our knowledge on the critical biological pathways involved in disease progression by characterizing in vivo processes at a cellular and molecular level and enabling significant improvements in the understanding of the etiology of IBD. This review presents a critical and updated overview on the imaging advances in animal models of IBD. Our aim is to highlight the potential beneficial impact and the range of applications that imaging techniques could offer for the improvement of the clinical monitoring and management of IBD patients: diagnosis, staging, determination of therapeutic targets, monitoring therapy and evaluation of the prognosis, personalized therapeutic approaches.

The benefits of paired-agent imaging in molecular-guided surgery: an update on methods and applications (Conference Presentation)

NASA Astrophysics Data System (ADS)

Tichauer, Kenneth M.

2016-03-01

One of the major complications with conventional imaging-agent-based molecular imaging, particularly for cancer imaging, is variability in agent delivery and nonspecific retention in biological tissue. Such factors can account to "swamp" the signal arising from specifically bound imaging agent, which is presumably indicative of the concentration of targeted biomolecule. In the 1950s, Pressman et al. proposed a method of accounting for these delivery and retention effects by normalizing targeted antibody retention to the retention of a co-administered "untargeted"/control imaging agent [1]. Our group resurrected the approach within the last 5 years, finding ways to utilize this so-called "paired-agent" imaging approach to directly quantify biomolecule concentration in tissue (in vitro, ex vivo, and in vivo) [2]. These novel paired-agent imaging approaches capable of quantifying biomolecule concentration provide enormous potential for being adapted to and optimizing molecular-guided surgery, which has a principle goal of identifying distinct biological tissues (tumor, nerves, etc…) based on their distinct molecular environment. This presentation will cover the principles and nuances of paired-agent imaging, as well as the current status of the field and future applications. [1] D. Pressman, E. D. Day, and M. Blau, "The use of paired labeling in the determination of tumor-localizing antibodies," Cancer Res, 17(9), 845-50 (1957). [2] K. M. Tichauer, Y. Wang, B. W. Pogue et al., "Quantitative in vivo cell-surface receptor imaging in oncology: kinetic modeling and paired-agent principles from nuclear medicine and optical imaging," Phys Med Biol, 60(14), R239-69 (2015).

Identification of regions of normal grey matter and white matter from pathologic glioblastoma and necrosis in frozen sections using Raman imaging.

PubMed

Kast, Rachel; Auner, Gregory; Yurgelevic, Sally; Broadbent, Brandy; Raghunathan, Aditya; Poisson, Laila M; Mikkelsen, Tom; Rosenblum, Mark L; Kalkanis, Steven N

2015-11-01

In neurosurgical applications, a tool capable of distinguishing grey matter, white matter, and areas of tumor and/or necrosis in near-real time could greatly aid in tumor resection decision making. Raman spectroscopy is a non-destructive spectroscopic technique which provides molecular information about the tissue under examination based on the vibrational properties of the constituent molecules. With careful measurement and data processing, a spatial step and repeat acquisition of Raman spectra can be used to create Raman images. Forty frozen brain tissue sections were imaged in their entirety using a 300-µm-square measurement grid, and two or more regions of interest within each tissue were also imaged using a 25 µm-square step size. Molecular correlates for histologic features of interest were identified within the Raman spectra, and novel imaging algorithms were developed to compare molecular features across multiple tissues. In previous work, the relative concentration of individual biomolecules was imaged. Here, the relative concentrations of 1004, 1300:1344, and 1660 cm(-1), which correspond primarily to protein and lipid content, were simultaneously imaged across all tissues. This provided simple interpretation of boundaries between grey matter, white matter, and diseased tissue, and corresponded with findings from adjacent hematoxylin and eosin-stained sections. This novel, yet simple, multi-channel imaging technique allows clinically-relevant resolution with straightforward molecular interpretation of Raman images not possible by imaging any single peak. This method can be applied to either surgical or laboratory tools for rapid, non-destructive imaging of grey and white matter.

Fab(nimotuzumab)-HYNIC-99mTc: Antibody Fragmentation for Molecular Imaging Agents.

PubMed

Calzada, Victoria; García, María Fernanda; Alonso-Martínez, Luis Michel; Camachoc, Ximena; Goicochea, Enzo; Fernández, Marcelo; Castillo, Abmel Xiques; Díaz-Miqueli, Arlhee; Iznaga-Escobar, Normando; Montaña, René Leyva; Alonso, Omar; Gambini, Juan Pablo; Cabral, Pablo

2016-01-01

Finally, fast blood clearance nimotuzumab is a humanized monoclonal antibody that recognise, with high specific affinity, the epidermal growth factor receptor (EGF-R) which play an important role in the growth process associated with many solid tumors. In this work, the whole antibody was digested with papain in order to generate a Fab fragment, derivatized with NHS-HYNIC-Tfa and radiolabel with technetium-99m (99mTc) as a potential agent of molecular imaging of cancer. Both, whole and fragment radiolabels were in-vivo and in-vitro characterized. Radiolabeling conditions with Tricine as coligand and quality controls were assessed to confirm the integrity of the labeled fragment. Biodistribution and imaging studies in normal and spontaneous adenocarcinoma mice were performed at different times to determine the in-vivo characteristics of the radiolabel fragment. Tumor localization was visualized by conventional gamma camera imaging studies, and the results were compared with the whole antibody. Also, an immunoreactivity assay was carried out for both. The results showed clearly the integrity of the nimotuzumab fragment and the affinity by the receptor was verified. Fab(nimotuzumab)-HYNIC was obtained with high purity and a simple strategy of radiolabeling was performed. Finally, a fast blood clearance was observed in the biodistribution studies increasing the tumor uptake of Fab(nimotuzumab)- HYNIC-99mTc over time, with tumor/muscle ratios of 3.81 ± 0.50, 5.16 ± 1.97 and 6.32 ± 1.98 at 1 h, 4 h and 24 h post injection. Urinary excretion resulted in 32.89 ± 3.91 %ID eliminated at 24 h. Scintigraphy images showed uptake in the tumor and the activity in non-target organs was consistent with the biodistribution data at the same time points. Hence, these preliminary results showed important further characteristic of Fab(nimotuzumab)-HYNIC-99mTc as a molecular imaging agent of cancer.

Companion diagnostics and molecular imaging-enhanced approaches for oncology clinical trials.

PubMed

Van Heertum, Ronald L; Scarimbolo, Robert; Ford, Robert; Berdougo, Eli; O'Neal, Michael

2015-01-01

In the era of personalized medicine, diagnostic approaches are helping pharmaceutical and biotechnology sponsors streamline the clinical trial process. Molecular assays and diagnostic imaging are routinely being used to stratify patients for treatment, monitor disease, and provide reliable early clinical phase assessments. The importance of diagnostic approaches in drug development is highlighted by the rapidly expanding global cancer diagnostics market and the emergent attention of regulatory agencies worldwide, who are beginning to offer more structured platforms and guidance for this area. In this paper, we highlight the key benefits of using companion diagnostics and diagnostic imaging with a focus on oncology clinical trials. Nuclear imaging using widely available radiopharmaceuticals in conjunction with molecular imaging of oncology targets has opened the door to more accurate disease assessment and the modernization of standard criteria for the evaluation, staging, and treatment responses of cancer patients. Furthermore, the introduction and validation of quantitative molecular imaging continues to drive and optimize the field of oncology diagnostics. Given their pivotal role in disease assessment and treatment, the validation and commercialization of diagnostic tools will continue to advance oncology clinical trials, support new oncology drugs, and promote better patient outcomes.

Mesoscopic Fluorescence Molecular Tomography for Evaluating Engineered Tissues.

PubMed

Ozturk, Mehmet S; Chen, Chao-Wei; Ji, Robin; Zhao, Lingling; Nguyen, Bao-Ngoc B; Fisher, John P; Chen, Yu; Intes, Xavier

2016-03-01

Optimization of regenerative medicine strategies includes the design of biomaterials, development of cell-seeding methods, and control of cell-biomaterial interactions within the engineered tissues. Among these steps, one paramount challenge is to non-destructively image the engineered tissues in their entirety to assess structure, function, and molecular expression. It is especially important to be able to enable cell phenotyping and monitor the distribution and migration of cells throughout the bulk scaffold. Advanced fluorescence microscopic techniques are commonly employed to perform such tasks; however, they are limited to superficial examination of tissue constructs. Therefore, the field of tissue engineering and regenerative medicine would greatly benefit from the development of molecular imaging techniques which are capable of non-destructive imaging of three-dimensional cellular distribution and maturation within a tissue-engineered scaffold beyond the limited depth of current microscopic techniques. In this review, we focus on an emerging depth-resolved optical mesoscopic imaging technique, termed laminar optical tomography (LOT) or mesoscopic fluorescence molecular tomography (MFMT), which enables longitudinal imaging of cellular distribution in thick tissue engineering constructs at depths of a few millimeters and with relatively high resolution. The physical principle, image formation, and instrumentation of LOT/MFMT systems are introduced. Representative applications in tissue engineering include imaging the distribution of human mesenchymal stem cells embedded in hydrogels, imaging of bio-printed tissues, and in vivo applications.

Imaging of Tumor Characteristics and Molecular Pathways With PET: Developments Over the Last Decade Toward Personalized Cancer Therapy.

PubMed

Marcu, Loredana Gabriela; Moghaddasi, Leyla; Bezak, Eva

2018-05-04

Improvements in personalized therapy are made possible by the advances in molecular biology that led to developments in molecular imaging, allowing highly specific in vivo imaging of biological processes. Positron emission tomography (PET) is the most specific and sensitive imaging technique for in vivo molecular targets and pathways, offering quantification and evaluation of functional properties of the targeted anatomy. This work is an integrative research review that summarizes and evaluates the accumulated current status of knowledge of recent advances in PET imaging for cancer diagnosis and treatment, concentrating on novel radiotracers and evaluating their advantages and disadvantages in cancer characterization. Medline search was conducted, limited to English publications from 2007 onward. Identified manuscripts were evaluated for most recent developments in PET imaging of cancer hypoxia, angiogenesis, proliferation, and clonogenic cancer stem cells (CSC). There is an expansion observed from purely metabolic-based PET imaging toward antibody-based PET to achieve more information on cancer characteristics to identify hypoxia, proangiogenic factors, CSC, and others. 64 Cu-ATSM, for example, can be used both as a hypoxia and a CSC marker. Progress in the field of functional imaging will possibly lead to more specific tumor targeting and personalized treatment, increasing tumor control and improving quality of life. Copyright © 2018 Elsevier Inc. All rights reserved.

Photothermal optical coherence tomography of epidermal growth factor receptor in live cells using immunotargeted gold nanospheres

NASA Astrophysics Data System (ADS)

Skala, Melissa C.; Crow, Matthew J.; Wax, Adam; Izatt, Joseph A.

2009-02-01

Molecular imaging is a powerful tool for investigating disease processes and potential therapies in both in vivo and in vitro systems. However, high resolution molecular imaging has been limited to relatively shallow penetration depths that can be accessed with microscopy. Optical coherence tomography (OCT) is an optical analogue to ultrasound with relatively good penetration depth (1-2 mm) and resolution (~1-10 μm). We have developed and characterized photothermal OCT as a molecular contrast mechanism that allows for high resolution molecular imaging at deeper penetration depths than microscopy. Our photothermal system consists of an amplitude-modulated heating beam that spatially overlaps with the focused spot of the sample arm of a spectral-domain OCT microscope. Validation experiments in tissue-like phantoms containing gold nanospheres that absorb at 532 nm revealed a sensitivity of 14 parts per million nanospheres (weight/weight) in a tissue-like environment. The nanospheres were then conjugated to anti-EGFR, and molecular targeting was confirmed in cells that over-express EGFR (MDA-MB-468) and cells that express low levels of EGFR (MDA-MB-435). Molecular imaging in three-dimensional tissue constructs was confirmed with a significantly lower photothermal signal (p<0.0001) from the constructs composed of cells that express low levels of EGFR compared to the over-expressing cell constructs (300% signal increase). This technique could potentially augment confocal and multiphoton microscopy as a method for deep-tissue, depth-resolved molecular imaging with relatively high resolution and target sensitivity, without photobleaching or cytotoxicity.

Quantum dots versus organic fluorophores in fluorescent deep-tissue imaging--merits and demerits.

PubMed

Bakalova, Rumiana; Zhelev, Zhivko; Gadjeva, Veselina

2008-12-01

The use of fluorescence in deep-tissue imaging is rapidly expanding in last several years. The progress in fluorescent molecular probes and fluorescent imaging techniques gives an opportunity to detect single cells and even molecular targets in live organisms. The highly sensitive and high-speed fluorescent molecular sensors and detection devices allow the application of fluorescence in functional imaging. With the development of novel bright fluorophores based on nanotechnologies and 3D fluorescence scanners with high spatial and temporal resolution, the fluorescent imaging has a potential to become an alternative of the other non-invasive imaging techniques as magnetic resonance imaging, positron-emission tomography, X-ray, computing tomography. The fluorescent imaging has also a potential to give a real map of human anatomy and physiology. The current review outlines the advantages of fluorescent nanoparticles over conventional organic dyes in deep-tissue imaging in vivo and defines the major requirements to the "perfect fluorophore". The analysis proceeds from the basic principles of fluorescence and major characteristics of fluorophores, light-tissue interactions, and major limitations of fluorescent deep-tissue imaging. The article is addressed to a broad readership - from specialists in this field to university students.

Magnetic resonance-coupled fluorescence tomography scanner for molecular imaging of tissue

NASA Astrophysics Data System (ADS)

Davis, Scott C.; Pogue, Brian W.; Springett, Roger; Leussler, Christoph; Mazurkewitz, Peter; Tuttle, Stephen B.; Gibbs-Strauss, Summer L.; Jiang, Shudong S.; Dehghani, Hamid; Paulsen, Keith D.

2008-06-01

A multichannel spectrally resolved optical tomography system to image molecular targets in small animals from within a clinical MRI is described. Long source/detector fibers operate in contact mode and couple light from the tissue surface in the magnet bore to 16 spectrometers, each containing two optical gratings optimized for the near infrared wavelength range. High sensitivity, cooled charge coupled devices connected to each spectrograph provide detection of the spectrally resolved signal, with exposure times that are automated for acquisition at each fiber. The design allows spectral fitting of the remission light, thereby separating the fluorescence signal from the nonspecific background, which improves the accuracy and sensitivity when imaging low fluorophore concentrations. Images of fluorescence yield are recovered using a nonlinear reconstruction approach based on the diffusion approximation of photon propagation in tissue. The tissue morphology derived from the MR images serves as an imaging template to guide the optical reconstruction algorithm. Sensitivity studies show that recovered values of indocyanine green fluorescence yield are linear to concentrations of 1nM in a 70mm diameter homogeneous phantom, and detection is feasible to near 10pM. Phantom data also demonstrate imaging capabilities of imperfect fluorophore uptake in tissue volumes of clinically relevant sizes. A unique rodent MR coil provides optical fiber access for simultaneous optical and MR data acquisition of small animals. A pilot murine study using an orthotopic glioma tumor model demonstrates optical-MRI imaging of an epidermal growth factor receptor targeted fluorescent probe in vivo.

A novel small molecule mediate 18F-FDG excited fluorescence molecular imaging

NASA Astrophysics Data System (ADS)

Zhang, Zeyu; Guo, Hongbo; Hu, Zhenhua; Tian, Jie

2018-02-01

Fluorescence molecular imaging (FMI) has been widely used in many medical fields with small molecule indocyanine green (ICG). However, low signal-background ratio and limited specificity to tumor remain big challenges for FMI. In this study, a novel excitation strategy is proposed on the basis of clinical approved ICG and 18F-FDG. A series of in vitro experiments are designed to reveal the mechanism and results show obvious decreasing of ICG fluorescence intensity with the increasing distance to excitation source. Meanwhile, the ICG fluorescence intensity is proportional to the activity of radiopharmaceutical. Results from different respects illustrate the promising of this proposed excitation strategy.

Non-invasive Optical Molecular Imaging for Cancer Detection

NASA Astrophysics Data System (ADS)

Luo, Zhen

Cancer is a leading cause of death worldwide. It remains the second most common cause of death in the US, accounting for nearly 1 out of every 4 deaths. Improved fundamental understanding of molecular processes and pathways resulting in cancer development has catalyzed a shift towards molecular analysis of cancer using imaging technologies. It is expected that the non-invasive or minimally invasive molecular imaging analysis of cancer can significantly aid in improving the early detection of cancer and will result in reduced mortality and morbidity associated with the disease. The central hypothesis of the proposed research is that non-invasive imaging of changes in metabolic activity of individual cells, and extracellular pH within a tissue will improve early stage detection of cancer. The specific goals of this research project were to: (a) develop novel optical imaging probes to image changes in choline metabolism and tissue pH as a function of progression of cancer using clinically isolated tissue biopsies; (b) correlate changes in tissue extracellular pH and metabolic activity of tissues as a function of disease state using clinically isolated tissue biopsies; (c) provide fundamental understanding of relationship between tumor hypoxia, acidification of the extracellular space and altered cellular metabolism with progression of cancer. Three novel molecular imaging probes were developed to detect changes in choline and glucose metabolism and extracellular pH in model systems and clinically isolated cells and biopsies. Glucose uptake and metabolism was measured using a fluorescence analog of glucose, 2-NBDG (2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxy-D-glucose), while choline metabolism was measured using a click chemistry analog of choline, propargyl choline, which can be in-situ labeled with a fluorophore Alexa-488 azide via a click chemistry reaction. Extracellular pH in tissue were measured by Alexa-647 labeled pHLIP (pH low insertion peptide), which can selectively target plasma membrane of cells based on lower extracellular pH. 20 pairs of clinically normal and abnormal biopsies were obtained from consenting patients at UCDMC. Fluorescence intensity of tissue biopsies before and after topical delivery of 2-NBDG and Alexa-647 labeled pHLIP was measured non-invasively by widefield imaging and confocal microscope. Uptake of propargyl choline was measured after topical delivery using confocal microscope. The results of all three molecular imagine probes were further correlated with pathological diagnosis. The imaging results of clinical biopsies demonstrated that 2-NBDG, propargyl choline and pHLIP peptide can accurately distinguish the pathologically normal and abnormal biopsies. Topical application of the contrast agents generated significantly higher fluorescence signal intensity in all neoplastic tissues as compared to clinically normal biopsies irrespective of the anatomic location or patient. This unpaired comparison across all the cancer patients in this study highlights the specificity of the imaging approach. Furthermore, the results indicated that changes in intracellular glucose, choline metabolism and cancer acidosis are initiated in the early stages of cancer and these changes are correlated with the progression of the disease. In conclusion, these novel optical molecular imaging approaches to measure multiple biomarkers in cancer have significant potential to be a useful tool for improving early detection and prognostic evaluation of oral neoplasia.

A novel high resolution, high sensitivity SPECT detector for molecular imaging of cardiovascular diseases

NASA Astrophysics Data System (ADS)

Cusanno, F.; Argentieri, A.; Baiocchi, M.; Colilli, S.; Cisbani, E.; De Vincentis, G.; Fratoni, R.; Garibaldi, F.; Giuliani, F.; Gricia, M.; Lucentini, M.; Magliozzi, M. L.; Majewski, S.; Marano, G.; Musico, P.; Musumeci, M.; Santavenere, F.; Torrioli, S.; Tsui, B. M. W.; Vitelli, L.; Wang, Y.

2010-05-01

Cardiovascular diseases are the most common cause of death in western countries. Understanding the rupture of vulnerable atherosclerotic plaques and monitoring the effect of innovative therapies of heart failure is of fundamental importance. A flexible, high resolution, high sensitivity detector system for molecular imaging with radionuclides on small animal models has been designed for this aim. A prototype has been built using tungsten pinhole and LaBr3(Ce) scintillator coupled to Hamamatsu Flat Panel PMTs. Compact individual-channel readout has been designed, built and tested. Measurements with phantoms as well as pilot studies on mice have been performed, the results show that the myocardial perfusion in mice can be determined with sufficient precision. The detector will be improved replacing the Hamamatsu Flat Panel with Silicon Photomultipliers (SiPMs) to allow integration of the system with MRI scanners. Application of LaBr3(Ce) scintillator coupled to photosensor with high photon detection efficiency and excellent energy resolution will allow dual-label imaging to monitor simultaneously the cardiac perfusion and the molecular targets under investigation during the heart therapy.

Vision 20/20: Molecular-guided surgical oncology based upon tumor metabolism or immunologic phenotype: Technological pathways for point of care imaging and intervention

PubMed Central

Paulsen, Keith D.; Samkoe, Kimberley S.; Elliott, Jonathan T.; Hasan, Tayyaba; Strong, Theresa V.; Draney, Daniel R.; Feldwisch, Joachim

2016-01-01

Surgical guidance with fluorescence has been demonstrated in individual clinical trials for decades, but the scientific and commercial conditions exist today for a dramatic increase in clinical value. In the past decade, increased use of indocyanine green based visualization of vascular flow, biliary function, and tissue perfusion has spawned a robust growth in commercial systems that have near-infrared emission imaging and video display capabilities. This recent history combined with major preclinical innovations in fluorescent-labeled molecular probes, has the potential for a shift in surgical practice toward resection guidance based upon molecular information in addition to conventional visual and palpable cues. Most surgical subspecialties already have treatment management decisions partially based upon the immunohistochemical phenotype of the cancer, as assessed from molecular pathology of the biopsy tissue. This phenotyping can inform the surgical resection process by spatial mapping of these features. Further integration of the diagnostic and therapeutic value of tumor metabolism sensing molecules or immune binding agents directly into the surgical process can help this field mature. Maximal value to the patient would come from identifying the spatial patterns of molecular expression in vivo that are well known to exist. However, as each molecular agent is advanced into trials, the performance of the imaging system can have a critical impact on the success. For example, use of pre-existing commercial imaging systems are not well suited to image receptor targeted fluorophores because of the lower concentrations expected, requiring orders of magnitude more sensitivity. Additionally the imaging system needs the appropriate dynamic range and image processing features to view molecular probes or therapeutics that may have nonspecific uptake or pharmacokinetic issues which lead to limitations in contrast. Imaging systems need to be chosen based upon objective performance criteria, and issues around calibration, validation, and interpretation need to be established before a clinical trial starts. Finally, as early phase trials become more established, the costs associated with failures can be crippling to the field, and so judicious use of phase 0 trials with microdose levels of agents is one viable paradigm to help the field advance, but this places high sensitivity requirements on the imaging systems used. Molecular-guided surgery has truly transformative potential, and several key challenges are outlined here with the goal of seeing efficient advancement with ideal choices. The focus of this vision 20/20 paper is on the technological aspects that are needed to be paired with these agents. PMID:27277060

Vision 20/20: Molecular-guided surgical oncology based upon tumor metabolism or immunologic phenotype: Technological pathways for point of care imaging and intervention.

PubMed

Pogue, Brian W; Paulsen, Keith D; Samkoe, Kimberley S; Elliott, Jonathan T; Hasan, Tayyaba; Strong, Theresa V; Draney, Daniel R; Feldwisch, Joachim

2016-06-01

Surgical guidance with fluorescence has been demonstrated in individual clinical trials for decades, but the scientific and commercial conditions exist today for a dramatic increase in clinical value. In the past decade, increased use of indocyanine green based visualization of vascular flow, biliary function, and tissue perfusion has spawned a robust growth in commercial systems that have near-infrared emission imaging and video display capabilities. This recent history combined with major preclinical innovations in fluorescent-labeled molecular probes, has the potential for a shift in surgical practice toward resection guidance based upon molecular information in addition to conventional visual and palpable cues. Most surgical subspecialties already have treatment management decisions partially based upon the immunohistochemical phenotype of the cancer, as assessed from molecular pathology of the biopsy tissue. This phenotyping can inform the surgical resection process by spatial mapping of these features. Further integration of the diagnostic and therapeutic value of tumor metabolism sensing molecules or immune binding agents directly into the surgical process can help this field mature. Maximal value to the patient would come from identifying the spatial patterns of molecular expression in vivo that are well known to exist. However, as each molecular agent is advanced into trials, the performance of the imaging system can have a critical impact on the success. For example, use of pre-existing commercial imaging systems are not well suited to image receptor targeted fluorophores because of the lower concentrations expected, requiring orders of magnitude more sensitivity. Additionally the imaging system needs the appropriate dynamic range and image processing features to view molecular probes or therapeutics that may have nonspecific uptake or pharmacokinetic issues which lead to limitations in contrast. Imaging systems need to be chosen based upon objective performance criteria, and issues around calibration, validation, and interpretation need to be established before a clinical trial starts. Finally, as early phase trials become more established, the costs associated with failures can be crippling to the field, and so judicious use of phase 0 trials with microdose levels of agents is one viable paradigm to help the field advance, but this places high sensitivity requirements on the imaging systems used. Molecular-guided surgery has truly transformative potential, and several key challenges are outlined here with the goal of seeing efficient advancement with ideal choices. The focus of this vision 20/20 paper is on the technological aspects that are needed to be paired with these agents.

Metabolic Imaging in Parkinson Disease.

PubMed

Meles, Sanne K; Teune, Laura K; de Jong, Bauke M; Dierckx, Rudi A; Leenders, Klaus L

2017-01-01

This review focuses on recent human 18 F-FDG PET studies in Parkinson disease. First, an overview is given of the current analytic approaches to metabolic brain imaging data. Next, we discuss how 18 F-FDG PET studies have advanced understanding of the relation between distinct brain regions and associated symptoms in Parkinson disease, including cognitive decline. In addition, the value of 18 F-FDG PET studies in differential diagnosis, identifying prodromal patients, and the evaluation of treatment effects are reviewed. Finally, anticipated developments in the field are addressed. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

Future and Advances in Endoscopy

PubMed Central

Elahi, Sakib F.; Wang, Thomas D.

2012-01-01

The future of endoscopy will be dictated by rapid technological advances in the development of light sources, optical fibers, and miniature scanners that will allow for images to be collected in multiple spectral regimes, with greater tissue penetration, and in three dimensions. These engineering breakthroughs will be integrated with novel molecular probes that are highly specific for unique proteins to target diseased tissues. Applications include early cancer detection by imaging molecular changes that occur before gross morphological abnormalities, personalized medicine by visualizing molecular targets specific to individual patients, and image guided therapy by localizing tumor margins and monitoring for recurrence. PMID:21751414

The Development and Comparison of Molecular Dynamics Simulation and Monte Carlo Simulation

NASA Astrophysics Data System (ADS)

Chen, Jundong

2018-03-01

Molecular dynamics is an integrated technology that combines physics, mathematics and chemistry. Molecular dynamics method is a computer simulation experimental method, which is a powerful tool for studying condensed matter system. This technique not only can get the trajectory of the atom, but can also observe the microscopic details of the atomic motion. By studying the numerical integration algorithm in molecular dynamics simulation, we can not only analyze the microstructure, the motion of particles and the image of macroscopic relationship between them and the material, but can also study the relationship between the interaction and the macroscopic properties more conveniently. The Monte Carlo Simulation, similar to the molecular dynamics, is a tool for studying the micro-molecular and particle nature. In this paper, the theoretical background of computer numerical simulation is introduced, and the specific methods of numerical integration are summarized, including Verlet method, Leap-frog method and Velocity Verlet method. At the same time, the method and principle of Monte Carlo Simulation are introduced. Finally, similarities and differences of Monte Carlo Simulation and the molecular dynamics simulation are discussed.

Molecular Imaging in Nanotechnology and Theranostics.

PubMed

Andreou, Chrysafis; Pal, Suchetan; Rotter, Lara; Yang, Jiang; Kircher, Moritz F

2017-06-01

The fields of biomedical nanotechnology and theranostics have enjoyed exponential growth in recent years. The "Molecular Imaging in Nanotechnology and Theranostics" (MINT) Interest Group of the World Molecular Imaging Society (WMIS) was created in order to provide a more organized and focused forum on these topics within the WMIS and at the World Molecular Imaging Conference (WMIC). The interest group was founded in 2015 and was officially inaugurated during the 2016 WMIC. The overarching goal of MINT is to bring together the many scientists who work on molecular imaging approaches using nanotechnology and those that work on theranostic agents. MINT therefore represents scientists, labs, and institutes that are very diverse in their scientific backgrounds and areas of expertise, reflecting the wide array of materials and approaches that drive these fields. In this short review, we attempt to provide a condensed overview over some of the key areas covered by MINT. Given the breadth of the fields and the given space constraints, we have limited the coverage to the realm of nanoconstructs, although theranostics is certainly not limited to this domain. We will also focus only on the most recent developments of the last 3-5 years, in order to provide the reader with an intuition of what is "in the pipeline" and has potential for clinical translation in the near future.

Application of molecular imaging combined with genetic screening in diagnosing MELAS, diabetes and recurrent pancreatitis.

PubMed

Zhiping, W; Quwen, L; Hai, Z; Jian, Z; Peiyi, G

2016-01-01

We report molecular imaging combined with gene diagnosis in a family with 7 members who carried an A3243G mutation in mitochondrial tRNA and p.Thr 137 Met in cationic trypsinogen (PRSS1) gene presented with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS), diabetes, and recurrent pancreatitis. DNA sequencing was used to detect and validate mitochondrial DNA and PRSS1. We also verified that mitochondrial heterozygous mutations and c.410 C>T mutation causing p.Thr 137 Met could be detected in oral epithelial cells or in urine sediment cells. In addition, molecular imaging was carried out in the affected family members. In this pedigree, MELAS syndrome accompanied by pancreatitis was an important clinical feature, followed by diabetes. Heteroplasmy of the mtDNA A3243G and c.410 C>T mutation of PRSS1 was found in all tissue samples of these patients, but no mutations were found in 520 normal control and normal individuals of the family. However, based on molecular imaging observations, patients with relatively higher lactate/pyruvate levels had more typical and more severe symptoms, particularly those of pancreatic disease (diabetes or pancreatitis). MELAS syndrome may be associated with pancreatitis. For the diagnosis, it is more reasonable to perform molecular imaging combined with gene diagnosis.

Precision medicine and molecular imaging: new targeted approaches toward cancer therapeutic and diagnosis.

PubMed

Ghasemi, Mojtaba; Nabipour, Iraj; Omrani, Abdolmajid; Alipour, Zeinab; Assadi, Majid

2016-01-01

This paper presents a review of the importance and role of precision medicine and molecular imaging technologies in cancer diagnosis with therapeutics and diagnostics purposes. Precision medicine is progressively becoming a hot topic in all disciplines related to biomedical investigation and has the capacity to become the paradigm for clinical practice. The future of medicine lies in early diagnosis and individually appropriate treatments, a concept that has been named precision medicine, i.e. delivering the right treatment to the right patient at the right time. Molecular imaging is quickly being recognized as a tool with the potential to ameliorate every aspect of cancer treatment. On the other hand, emerging high-throughput technologies such as omics techniques and systems approaches have generated a paradigm shift for biological systems in advanced life science research. In this review, we describe the precision medicine, difference between precision medicine and personalized medicine, precision medicine initiative, systems biology/medicine approaches (such as genomics, radiogenomics, transcriptomics, proteomics, and metabolomics), P4 medicine, relationship between systems biology/medicine approaches and precision medicine, and molecular imaging modalities and their utility in cancer treatment and diagnosis. Accordingly, the precision medicine and molecular imaging will enable us to accelerate and improve cancer management in future medicine.

Precision medicine and molecular imaging: new targeted approaches toward cancer therapeutic and diagnosis

PubMed Central

Ghasemi, Mojtaba; Nabipour, Iraj; Omrani, Abdolmajid; Alipour, Zeinab; Assadi, Majid

2016-01-01

This paper presents a review of the importance and role of precision medicine and molecular imaging technologies in cancer diagnosis with therapeutics and diagnostics purposes. Precision medicine is progressively becoming a hot topic in all disciplines related to biomedical investigation and has the capacity to become the paradigm for clinical practice. The future of medicine lies in early diagnosis and individually appropriate treatments, a concept that has been named precision medicine, i.e. delivering the right treatment to the right patient at the right time. Molecular imaging is quickly being recognized as a tool with the potential to ameliorate every aspect of cancer treatment. On the other hand, emerging high-throughput technologies such as omics techniques and systems approaches have generated a paradigm shift for biological systems in advanced life science research. In this review, we describe the precision medicine, difference between precision medicine and personalized medicine, precision medicine initiative, systems biology/medicine approaches (such as genomics, radiogenomics, transcriptomics, proteomics, and metabolomics), P4 medicine, relationship between systems biology/medicine approaches and precision medicine, and molecular imaging modalities and their utility in cancer treatment and diagnosis. Accordingly, the precision medicine and molecular imaging will enable us to accelerate and improve cancer management in future medicine. PMID:28078184

Molecular and Cellular Quantitative Microscopy: theoretical investigations, technological developments and applications to neurobiology

NASA Astrophysics Data System (ADS)

Esposito, Alessandro

2006-05-01

This PhD project aims at the development and evaluation of microscopy techniques for the quantitative detection of molecular interactions and cellular features. The primarily investigated techniques are Fαrster Resonance Energy Transfer imaging and Fluorescence Lifetime Imaging Microscopy. These techniques have the capability to quantitatively probe the biochemical environment of fluorophores. An automated microscope capable of unsupervised operation has been developed that enables the investigation of molecular and cellular properties at high throughput levels and the analysis of cellular heterogeneity. State-of-the-art Förster Resonance Energy Transfer imaging, Fluorescence Lifetime Imaging Microscopy, Confocal Laser Scanning Microscopy and the newly developed tools have been combined with cellular and molecular biology techniques for the investigation of protein-protein interactions, oligomerization and post-translational modifications of α-Synuclein and Tau, two proteins involved in Parkinson’s and Alzheimer’s disease, respectively. The high inter-disciplinarity of this project required the merging of the expertise of both the Molecular Biophysics Group at the Debye Institute - Utrecht University and the Cell Biophysics Group at the European Neuroscience Institute - Gαttingen University. This project was conducted also with the support and the collaboration of the Center for the Molecular Physiology of the Brain (Göttingen), particularly with the groups associated with the Molecular Quantitative Microscopy and Parkinson’s Disease and Aggregopathies areas. This work demonstrates that molecular and cellular quantitative microscopy can be used in combination with high-throughput screening as a powerful tool for the investigation of the molecular mechanisms of complex biological phenomena like those occurring in neurodegenerative diseases.

In vivo bioluminescence imaging using orthotopic xenografts towards patient's derived-xenograft Medulloblastoma models.

PubMed

Asadzadeh, Fatemeh; Ferrucci, Veronica; DE Antonellis, Pasqualino; Zollo, Massimo

2017-03-01

Medulloblastoma is a cerebellar neoplasia of the central nervous system. Four molecular subgrups have been identified (MBWNT, MBSHH, MBgroup3 and MBgroup4) with distinct genetics and clinical outcome. Among these, MBgroup3-4 are highly metastatic with the worst prognosis. The current standard therapy includes surgery, radiation and chemotherapy. Thus, specific treatments adapted to cure those different molecular subgroups are needed. The use of orthotopic xenograft models, together with the non-invasive in vivo biolumiscence imaging (BLI) technology, is emerging during preclinical studies to test novel therapeutics for medulloblastoma treatment. Orthotopic MB xenografts were performed by injection of Daoy-luc cells, that had been previously infected with lentiviral particles to stably express luciferase gene, into the fourth right ventricle of the cerebellum of ten nude mice. For the implantation, specific stereotactic coordinates were used. Seven days after the implantation the mice were imaged by acquisitions of bioluminescence imaging (BLI) using IVIS 3D Illumina Imaging System (Xenogen). Tumor growth was evaluated by quantifying the bioluminescence signals using the integrated fluxes of photons within each area of interest using the Living Images Software Package 3.2 (Xenogen-Perkin Elmer). Finally, histological analysis using hematoxylin-eosin staining was performed to confirm the presence of tumorigenic cells into the cerebellum of the mice. We describe a method to use the in vivo bioluminescent imaging (BLI) showing the potential to be used to investigate the potential antitumorigenic effects of a drug for in vivo medulloblastoma treatment. We also discuss other studies in which this technology has been applied to obtain a more comprehensive knowledge of medulloblastoma using orthotopic xenograft mouse models. There is a need to develop patient's derived-xenograft (PDX) model systems to test novel drugs for medulloblastoma treatment within each molecular sub-groups with a higher predictive value. Here we show how this technology should be applied with hopes on generations of new treatments to be applied then in human.

Molecular Imaging for Breast Cancer Using Magnetic Resonance-Guided Positron Emission Mammography and Excitation-Resolved Near-Infrared Fluorescence Imaging

NASA Astrophysics Data System (ADS)

Cho, Jaedu

The aim of this work is to develop novel breast-specific molecular imaging techniques for management of breast cancer. In this dissertation, we describe two novel molecular imaging approaches for breast cancer management. In Part I, we introduce our multimodal molecular imaging approach for breast cancer therapy monitoring using magnetic resonance imaging and positron emission mammography (MR/PEM). We have focused on the therapy monitoring technique for aggressive cancer molecular subtypes, which is challenging due to time constraint. Breast cancer therapy planning relies on a fast and accurate monitoring of functional and anatomical change. We demonstrate a proof-of-concept of sequential dual-modal magnetic resonance and positron emission mammography (MR/PEM) for the cancer therapy monitoring. We have developed dedicated breast coils with breast compression mechanism equipped with MR-compatible PEM detector heads. We have designed a fiducial marker that allows straightforward image registration of data obtained from MRI and PEM. We propose an optimal multimodal imaging procedure for MR/PEM. In Part II, we have focused on the development of a novel intraoperative near-infrared fluorescence imaging system (NIRF) for image-guided breast cancer surgery. Conventional spectrally-resolved NIRF systems are unable to resolve various NIR fluorescence dyes for the following reasons. First, the fluorescence spectra of viable NIR fluorescence dyes are heavily overlapping. Second, conventional emission-resolved NIRF suffers from a trade-off between the fluence rate and the spectral resolution. Third, the multiple scattering in tissue degrades not only the spatial information but also the spectral contents by the red-shift. We develop a wavelength-swept laser-based NIRF system that can resolve the excitation shift of various NIR fluorescence dyes without substantial loss of the fluence rate. A linear ratiometric model is employed to measure the relative shift of the excitation spectrum of a fluorescence dye.

Diagnostics of Unseeded Air and Nitrogen Flows by Molecular Tagging

DTIC Science & Technology

2015-07-21

the polarization components across the FLEET line and the computed molecular density and dissociation fraction. Rayleigh Scattering Polarimetry V...Pol H Pol BPF HP CCM FLEET Emission Imaging Planar Rayleigh Scattering Rayleigh Scattering Polarimetry Density of molecules (normalized...the flow transport properties. This has been studied using Rayleigh scattering and Rayleigh scattering polarimetry . Figure 8 shows the evolution of

Critical Features of Visualizations of Transport through the Cell Membrane--an Empirical Study of Upper Secondary and Tertiary Students' Meaning-Making of a Still Image and an Animation

ERIC Educational Resources Information Center

Rundgren, Carl-Johan; Tibell, Lena A. E.

2010-01-01

Images, diagrams, and other forms of visualization are playing increasingly important roles in molecular life science teaching and research, both for conveying information and as conceptual tools, transforming the way we think about the events and processes the subject covers. This study examines how upper secondary and tertiary students interpret…

High-speed Raman-encoded molecular imaging of freshly excised tissue surfaces with topically applied SERRS nanoparticles

NASA Astrophysics Data System (ADS)

Wang, Yu "Winston"; Yang, Qian; Kang, Soyoung; Wall, Matthew A.; Liu, Jonathan T. C.

2018-04-01

Surface-enhanced Raman scattering (SERS) nanoparticles (NPs) are increasingly being engineered for a variety of disease-detection and treatment applications. For example, we have previously developed a fiber-optic Raman-encoded molecular imaging (REMI) system for spectral imaging of biomarker-targeted SERS NPs topically applied on tissue surfaces to identify residual tumors at surgical margins. Although accurate tumor detection was achieved, the commercial SERS NPs used in our previous studies lacked the signal strength to enable high-speed imaging with high pixel counts (large fields of view and/or high spatial resolution), which limits their use for certain time-constrained clinical applications. As a solution, we explored the use of surface-enhanced resonant Raman scattering (SERRS) NPs to enhance imaging speeds. The SERRS NPs were synthesized de novo, and then conjugated to HER2 antibodies to achieve high binding affinity, as validated by flow cytometry. Under identical tissue-staining and imaging conditions, the targeted SERRS NPs enabled reliable identification of HER2-overexpressed tumor xenografts with 50-fold-enhanced imaging speed compared with our standard targeted SERS NPs. This enables our REMI system to image tissue surfaces at a rate of 150 cm2 per minute at a spatial resolution of 0.5 mm.

In vivo high-resolution structural imaging of large arteries in small rodents using two-photon laser scanning microscopy

NASA Astrophysics Data System (ADS)

Megens, Remco T. A.; Reitsma, Sietze; Prinzen, Lenneke; Oude Egbrink, Mirjam G. A.; Engels, Wim; Leenders, Peter J. A.; Brunenberg, Ellen J. L.; Reesink, Koen D.; Janssen, Ben J. A.; Ter Haar Romeny, Bart M.; Slaaf, Dick W.; van Zandvoort, Marc A. M. J.

2010-01-01

In vivo (molecular) imaging of the vessel wall of large arteries at subcellular resolution is crucial for unraveling vascular pathophysiology. We previously showed the applicability of two-photon laser scanning microscopy (TPLSM) in mounted arteries ex vivo. However, in vivo TPLSM has thus far suffered from in-frame and between-frame motion artifacts due to arterial movement with cardiac and respiratory activity. Now, motion artifacts are suppressed by accelerated image acquisition triggered on cardiac and respiratory activity. In vivo TPLSM is performed on rat renal and mouse carotid arteries, both surgically exposed and labeled fluorescently (cell nuclei, elastin, and collagen). The use of short acquisition times consistently limit in-frame motion artifacts. Additionally, triggered imaging reduces between-frame artifacts. Indeed, structures in the vessel wall (cell nuclei, elastic laminae) can be imaged at subcellular resolution. In mechanically damaged carotid arteries, even the subendothelial collagen sheet (~1 μm) is visualized using collagen-targeted quantum dots. We demonstrate stable in vivo imaging of large arteries at subcellular resolution using TPLSM triggered on cardiac and respiratory cycles. This creates great opportunities for studying (diseased) arteries in vivo or immediate validation of in vivo molecular imaging techniques such as magnetic resonance imaging (MRI), ultrasound, and positron emission tomography (PET).

Deep-tissue reporter-gene imaging with fluorescence and optoacoustic tomography: a performance overview.

PubMed

Deliolanis, Nikolaos C; Ale, Angelique; Morscher, Stefan; Burton, Neal C; Schaefer, Karin; Radrich, Karin; Razansky, Daniel; Ntziachristos, Vasilis

2014-10-01

A primary enabling feature of near-infrared fluorescent proteins (FPs) and fluorescent probes is the ability to visualize deeper in tissues than in the visible. The purpose of this work is to find which is the optimal visualization method that can exploit the advantages of this novel class of FPs in full-scale pre-clinical molecular imaging studies. Nude mice were stereotactically implanted with near-infrared FP expressing glioma cells to from brain tumors. The feasibility and performance metrics of FPs were compared between planar epi-illumination and trans-illumination fluorescence imaging, as well as to hybrid Fluorescence Molecular Tomography (FMT) system combined with X-ray CT and Multispectral Optoacoustic (or Photoacoustic) Tomography (MSOT). It is shown that deep-seated glioma brain tumors are possible to visualize both with fluorescence and optoacoustic imaging. Fluorescence imaging is straightforward and has good sensitivity; however, it lacks resolution. FMT-XCT can provide an improved rough resolution of ∼1 mm in deep tissue, while MSOT achieves 0.1 mm resolution in deep tissue and has comparable sensitivity. We show imaging capacity that can shift the visualization paradigm in biological discovery. The results are relevant not only to reporter gene imaging, but stand as cross-platform comparison for all methods imaging near infrared fluorescent contrast agents.

Mass Spectrometry Imaging of low Molecular Weight Compounds in Garlic (Allium sativum L.) with Gold Nanoparticle Enhanced Target.

PubMed

Misiorek, Maria; Sekuła, Justyna; Ruman, Tomasz

2017-11-01

Garlic (Allium sativum) is the subject of many studies due to its numerous beneficial properties. Although compounds of garlic have been studied by various analytical methods, their tissue distributions are still unclear. Mass spectrometry imaging (MSI) appears to be a very powerful tool for the identification of the localisation of compounds within a garlic clove. Visualisation of the spatial distribution of garlic low-molecular weight compounds with nanoparticle-based MSI. Compounds occurring on the cross-section of sprouted garlic has been transferred to gold-nanoparticle enhanced target (AuNPET) by imprinting. The imprint was then subjected to MSI analysis. The results suggest that low molecular weight compounds, such as amino acids, dipeptides, fatty acids, organosulphur and organoselenium compounds are distributed within the garlic clove in a characteristic manner. It can be connected with their biological functions and metabolic properties in the plant. New methodology for the visualisation of low molecular weight compounds allowed a correlation to be made between their spatial distribution within a sprouted garlic clove and their biological function. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Estrogen receptor-targeted optical imaging of breast cancer cells with near-infrared fluorescent dye

NASA Astrophysics Data System (ADS)

Jose, Iven; Deodhar, Kodand; Chiplunkar, Shuba V.; Patkar, Meena

2010-02-01

Molecular imaging provides the in vivo characterization of cellular molecular events involved in normal and pathologic processes. With the advent of optical molecular imaging, specific molecules, proteins and genes may be tagged with a luminescent reporter and visualized in small animals. This powerful new tool has pushed in vivo optical imaging to the forefront as it allows for direct determination of drug bio-distribution and uptake kinetics as well as an indicator of biochemical activity and drug efficacy. Although optical imaging encompasses diverse techniques and makes use of various wavelengths of light, a great deal of excitement in molecular research lies in the use of tomographic and fluorescence techniques to image living tissues with near-infrared (NIR) light. Nonionizing, noninvasive near-infrared optical imaging has great potential to become promising alternative for breast cancer detection. Fluorescence spectroscopy studies of human tissue suggest that a variety of lesions show distinct fluorescence spectra compared to those of normal tissue. It has also been shown that exogenous dyes exhibit selective uptake in neoplastic lesions and may offer the best contrast for optical imaging. Use of exogenous agents would provide fluorescent markers, which could serve to detect embedded tumors in the breast. In particular, the ability to monitor the fluorescent yield and lifetime may also enable biochemical specificity if the fluorophore is sensitive to a specific metabolite, such as oxygen. As a first step, we have synthesized and characterized one such NIR fluorescent dye conjugate, which could potentially be used to detect estrogen receptors (ER)[2] . The conjugate was synthesized by ester formation between 17-β estradiol and a hydrophilic derivative of indocyanine green (ICG) cyanine dye, bis-1, 1-(4-sulfobutyl) indotricarbocyanine-5- carboxylic acid, sodium salt. The ester formed was found to have an extra binding ability with the receptor cites as compared to ICG, which was established by the partition coefficient studies. The replacement of the sodium ion in the ester by a larger glucosammonium ion was found to enhance the hydrophilicity and reduce the toxic effect on the cell lines. The excitation and emission peaks for the conjugate were recorded in the NIR region as 750nm and 788nm respectively. The ester was found nontoxic on adenocarcinoma breast cancer cell lines MCF-7/MDA-MB-231. Specific binding and endocytosis of the estrogen-labeled conjugate was studied on the MCF-7 (ER positive) and MDA-MB-231 (ER negative). Conjugate staining of MCF-7 cells showed ~ 4-fold increase in signal intensity compared to MDA-MB- 231. Further, estrogen molecules were found to be specifically localized to the nuclear region of MCF-7 cells, whereas MDA-MB-231 showed plasma membrane staining. This technique offers the potential of noninvasive detection of hormone receptor status in breast cancer cells and would help in decreasing the load of unnecessary biopsies. Here, we have reported the progress made in the development of a novel NIR external contrast agent and the work is in progress to use this conjugate for the molecular based, diagnostic imaging of breast cancer.

Rational Design of Molecular Ferroelectric Materials and Nanostructures

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ducharme, Stephen

2012-09-25

The purpose of this project was to gain insight into the properties of molecular ferroelectrics through the detailed study of oligomer analogs of polyvinylidene fluoride (PVDF). By focusing on interactions at both the molecular level and the nanoscale level, we expect to gain improved understanding about the fundamental mechanism of ferroelectricity and its key properties. The research consisted of three complementary components: 1) Rational synthesis of VDF oligomers by Prof. Takacs' group; 2) Detailed structural and electrical studies of thin by Prof. Ducharme's Group; and 3) First-principles computational studies by DOE Lab Partner Dr. Serge Nakhman-son at Argonne National Laboratory.more » The main results of the work was a detailed understanding of the relationships between the molecular interactions and macroscopic phenomenology of fer-roelectricity VDF oligomers. This is valuable information supporting the development of im-proved electromechanical materials for, e.g., sonar, ultrasonic imaging, artificial muscles, and compliant actuators. Other potential applications include nonvolatile ferroelectric memories, heat-sensing imaging arrays, photovoltaic devices, and functional biomimetic materials. The pro-ject contributed to the training and professional development of undergraduate students and graduate students, post-doctoral assistants, and a high-school teacher. Project personnel took part in several outreach and education activities each year.« less

Number and brightness image analysis reveals ATF-induced dimerization kinetics of uPAR in the cell membrane

PubMed Central

Hellriegel, Christian; Caiolfa, Valeria R.; Corti, Valeria; Sidenius, Nicolai; Zamai, Moreno

2011-01-01

We studied the molecular forms of the GPI-anchored urokinase plasminogen activator receptor (uPAR-mEGFP) in the human embryo kidney (HEK293) cell membrane and demonstrated that the binding of the amino-terminal fragment (ATF) of urokinase plasminogen activator is sufficient to induce the dimerization of the receptor. We followed the association kinetics and determined precisely the dimeric stoichiometry of uPAR-mEGFP complexes by applying number and brightness (N&B) image analysis. N&B is a novel fluctuation-based approach for measuring the molecular brightness of fluorophores in an image time sequence in live cells. Because N&B is very sensitive to long-term temporal fluctuations and photobleaching, we have introduced a filtering protocol that corrects for these important sources of error. Critical experimental parameters in N&B analysis are illustrated and analyzed by simulation studies. Control experiments are based on mEGFP-GPI, mEGFP-mEGFP-GPI, and mCherry-GPI, expressed in HEK293. This work provides a first direct demonstration of the dimerization of uPAR in live cells. We also provide the first methodological guide on N&B to discern minor changes in molecular composition such as those due to dimerization events, which are involved in fundamental cell signaling mechanisms.—Hellriegel, C., Caiolfa, V. R., Corti, V., Sidenius, N., Zamai, M. Number and brightness image analysis reveals ATF-induced dimerization kinetics of uPAR in the cell membrane. PMID:21602447

Molecular PET imaging for biology-guided adaptive radiotherapy of head and neck cancer.

PubMed

Hoeben, Bianca A W; Bussink, Johan; Troost, Esther G C; Oyen, Wim J G; Kaanders, Johannes H A M

2013-10-01

Integration of molecular imaging PET techniques into therapy selection strategies and radiation treatment planning for head and neck squamous cell carcinoma (HNSCC) can serve several purposes. First, pre-treatment assessments can steer decisions about radiotherapy modifications or combinations with other modalities. Second, biology-based objective functions can be introduced to the radiation treatment planning process by co-registration of molecular imaging with planning computed tomography (CT) scans. Thus, customized heterogeneous dose distributions can be generated with escalated doses to tumor areas where radiotherapy resistance mechanisms are most prevalent. Third, monitoring of temporal and spatial variations in these radiotherapy resistance mechanisms early during the course of treatment can discriminate responders from non-responders. With such information available shortly after the start of treatment, modifications can be implemented or the radiation treatment plan can be adapted tailing the biological response pattern. Currently, these strategies are in various phases of clinical testing, mostly in single-center studies. Further validation in multicenter set-up is needed. Ultimately, this should result in availability for routine clinical practice requiring stable production and accessibility of tracers, reproducibility and standardization of imaging and analysis methods, as well as general availability of knowledge and expertise. Small studies employing adaptive radiotherapy based on functional dynamics and early response mechanisms demonstrate promising results. In this context, we focus this review on the widely used PET tracer (18)F-FDG and PET tracers depicting hypoxia and proliferation; two well-known radiation resistance mechanisms.

Determining the Molecular Growth Mechanisms of Protein Crystal faces by Atomic Force Microscopy

NASA Technical Reports Server (NTRS)

Li, Huayu; Nadarajah, Arunan; Pusey, Marc L.

1998-01-01

A high resolution atomic force microscopy (AFM) study had shown that the molecular packing on the tetragonal lysozyme (110) face corresponded to only one of two possible packing arrangements, suggesting that growth layers on this face were of bimolecular height (Li et al., 1998). Theoretical analyses of the packing had also indicated that growth of this face should proceed by the addition of growth units of at least tetramer size corresponding to the 43 helices in the crystal. In this study an AFM linescan technique was devised to measure the dimensions of individual growth units on protein crystal faces. The growth process of tetragonal lysozyme crystals was slowed down by employing very low supersaturations. As a result images of individual growth events on the (110) face were observed, shown by jump discontinuities in the growth step in the linescan images. The growth unit dimension in the scanned direction was obtained by suitably averaging these images. A large number of scans in two directions on the (110) face were performed and the distribution of lysozyme aggregate sizes were obtained. A variety of growth units, all of which were 43 helical lysozyme aggregates, were shown to participate in the growth process with a 43 tetramer being the minimum observed size. This technique represents a new application for AFM allowing time resolved studies of molecular process to be carried out.

Monitoring of tumor growth and metastasis potential in MDA-MB-435s/ tk-luc human breast cancer xenografts

NASA Astrophysics Data System (ADS)

Chang, Ya-Fang; Lin, Yi-Yu; Wang, Hsin-Ell; Liu, Ren-Shen; Pang, Fei; Hwang, Jeng-Jong

2007-02-01

Molecular imaging of reporter gene expression provides a rapid, sensitive and non-invasive monitoring of tumor behaviors. In this study, we reported the establishment of a novel animal model for longitudinal examination of tumor growth kinetics and metastatic spreading in vivo. The highly metastatic human breast carcinoma MDA-MB-435s cell line was engineered to stably express herpes simplex virus type 1 thymidine kinase (HSV-1- tk) and luciferase ( luc). Both 131I-FIAU and D-luciferin were used as reporter probes. For orthotopic tumor formation, MDA-MB-435s/ tk-luc cells were implanted into the first nipple of 6-week-old female NOD/SCID mice. For metastatic study, cells were injected via the lateral tail vein. Mice-bearing MDA-MB-435s/ tk-luc tumors were scanned for tumor growth and metastatsis using Xenogen IVIS50 system. Gamma scintigraphy and whole-body autoradiography were also applied to confirm the tumor localization. The results of bioluminescence imaging as well as histopathological finding showed that tumors could be detected in femur, spine, ovary, lungs, kidney, adrenal gland, lymph nodes and muscle at 16 weeks post i.v. injection, and correlated photons could be quantified. This MDA-MB-435s/ tk-luc human breast carcinoma-bearing mouse model combined with multimodalities of molecular imaging may facilitate studies on the molecular mechanisms of cancer invasion and metastasis.

Noninvasive Detection and Imaging of Molecular Markers in Live Cardiomyocytes Derived from Human Embryonic Stem Cells

PubMed Central

Pascut, Flavius C.; Goh, Huey T.; Welch, Nathan; Buttery, Lee D.; Denning, Chris; Notingher, Ioan

2011-01-01

Raman microspectroscopy (RMS) was used to detect and image molecular markers specific to cardiomyocytes (CMs) derived from human embryonic stem cells (hESCs). This technique is noninvasive and thus can be used to discriminate individual live CMs within highly heterogeneous cell populations. Principal component analysis (PCA) of the Raman spectra was used to build a classification model for identification of individual CMs. Retrospective immunostaining imaging was used as the gold standard for phenotypic identification of each cell. We were able to discriminate CMs from other phenotypes with >97% specificity and >96% sensitivity, as calculated with the use of cross-validation algorithms (target 100% specificity). A comparison between Raman spectral images corresponding to selected Raman bands identified by the PCA model and immunostaining of the same cells allowed assignment of the Raman spectral markers. We conclude that glycogen is responsible for the discrimination of CMs, whereas myofibril proteins have a lesser contribution. This study demonstrates the potential of RMS for allowing the noninvasive phenotypic identification of hESC progeny. With further development, such label-free optical techniques may enable the separation of high-purity cell populations with mature phenotypes, and provide repeated measurements to monitor time-dependent molecular changes in live hESCs during differentiation in vitro. PMID:21190678

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fan, Quli; Cheng, Kai; Hu, Xiang

Developing multifunctional and easily prepared nanoplatforms with integrated different modalities is highly challenging for molecular imaging. Here, we report the successful transfer of an important molecular target, melanin, into a novel multimodality imaging nanoplatform. Melanin is abundantly expressed in melanotic melanomas and thus has been actively studied as a target for melanoma imaging. In our work, the multifunctional biopolymer nanoplatform based on ultrasmall (<10 nm) water-soluble melanin nanoparticle (MNP) was developed and showed unique photoacoustic property and natural binding ability with metal ions (for example, 64Cu 2+, Fe 3+). Therefore, MNP can serve not only as a photoacoustic contrast agent,more » but also as a nanoplatform for positron emission tomography (PET) and magnetic resonance imaging (MRI). Traditional passive nanoplatforms require complicated and time-consuming processes for prebuilding reporting moieties or chemical modifications using active groups to integrate different contrast properties into one entity. In comparison, utilizing functional biomarker melanin can greatly simplify the building process. We further conjugated α vβ 3 integrins, cyclic c(RGDfC) peptide, to MNPs to allow for U87MG tumor accumulation due to its targeting property combined with the enhanced permeability and retention (EPR) effect. As a result, the multimodal properties of MNPs demonstrate the high potential of endogenous materials with multifunctions as nanoplatforms for molecular theranostics and clinical translation.« less

Multimodal fluorescence molecular imaging for in vivo characterization of skin cancer using endogenous and exogenous fluorophores

NASA Astrophysics Data System (ADS)

Miller, Jessica P.; Habimana-Griffin, LeMoyne; Edwards, Tracy S.; Achilefu, Samuel

2017-06-01

Similarity of skin cancer with many benign skin pathologies requires reliable methods to detect and differentiate the different types of these lesions. Previous studies have explored the use of disparate optical techniques to identify and estimate the invasive nature of melanoma and basal cell carcinoma with varying outcomes. Here, we used a concerted approach that provides complementary information for rapid screening and characterization of tumors, focusing on squamous cell carcinoma (SCC) of the skin. Assessment of in vivo autofluorescence lifetime (FLT) imaging of endogenous fluorophores that are excitable at longer wavelengths (480 nm) than conventional NADH and FAD revealed a decrease in the short FLT component for SCC compared to normal skin, with mean values of 0.57±0.026 ns and 0.61±0.021 ns, respectively (p=0.004). Subsequent systemic administration of a near-infrared fluorescent molecular probe in SCC bearing mice, followed by the implementation of image processing methods on data acquired from two-dimensional and three-dimensional fluorescence molecular imaging, allowed us to estimate the tumor volume and depth, as well as quantify the fluorescent probe in the tumor. The result suggests the involvement of lipofuscin-like lipopigments and riboflavin in SCC metabolism and serves as a model for staging SCC.

Nanobubble-Affibody: Novel ultrasound contrast agents for targeted molecular ultrasound imaging of tumor.

PubMed

Yang, Hengli; Cai, Wenbin; Xu, Lei; Lv, Xiuhua; Qiao, Youbei; Li, Pan; Wu, Hong; Yang, Yilin; Zhang, Li; Duan, Yunyou

2015-01-01

Nanobubbles (NBs), as novel ultrasound contrast agents (UCAs), have attracted increasing attention in the field of molecular ultrasound imaging for tumors. However, the preparation of uniform-sized NBs is considered to be controversial, and poor tumor selectivity in in vivo imaging has been reported. In this study, we fabricated uniform nano-sized NBs (478.2 ± 29.7 nm with polydispersity index of 0.164 ± 0.044, n = 3) using a thin-film hydration method by controlling the thickness of phospholipid films; we then conjugated the NBs with Affibody molecules to produce nano-sized UCAs referred to as NB-Affibody with specific affinity to human epidermal growth factor receptor type 2 (HER2)-overexpressing tumors. NB-Affibody presented good ultrasound enhancement, demonstrating a peak intensity of 104.5 ± 2.1 dB under ultrasound contrast scanning. Ex vivo experiments further confirmed that the NB-Affibody conjugates were capable of targeting HER2-expressing tumor cells in vivo with high affinity. The newly prepared nano-sized NB-Affibody conjugates were observed to be novel targeted UCAs for efficient and safe specific molecular imaging and may have potential applications in early cancer quantitative diagnosis and targeted therapy in the future. Copyright © 2014 Elsevier Ltd. All rights reserved.

Fast deep-tissue multispectral optoacoustic tomography (MSOT) for preclinical imaging of cancer and cardiovascular disease

NASA Astrophysics Data System (ADS)

Taruttis, Adrian; Razansky, Daniel; Ntziachristos, Vasilis

2012-02-01

Optoacoustic imaging has enabled the visualization of optical contrast at high resolutions in deep tissue. Our Multispectral optoacoustic tomography (MSOT) imaging results reveal internal tissue heterogeneity, where the underlying distribution of specific endogenous and exogenous sources of absorption can be resolved in detail. Technical advances in cardiac imaging allow motion-resolved multispectral measurements of the heart, opening the way for studies of cardiovascular disease. We further demonstrate the fast characterization of the pharmacokinetic profiles of lightabsorbing agents. Overall, our MSOT findings indicate new possibilities in high resolution imaging of functional and molecular parameters.

Targeting Cell Surface Proteins in Molecular Photoacoustic Imaging to Detect Ovarian Cancer Early

DTIC Science & Technology

2013-07-01

biology, nanotechnology, and imaging technology, molecular imaging utilizes specific probes as contrast agents to visualize cellular processes at the...This reagent was covalently coupled to the oligosaccharides attached to polypeptide side-chains of extracellular membrane proteins on living cells...website. The normal tissue gene expression profile dataset was modified and processed as described by Fang (8) and mean intensities and standard

Molecular imaging with radionuclides, a powerful technique for studying biological processes in vivo

NASA Astrophysics Data System (ADS)

Cisbani, E.; Cusanno, F.; Garibaldi, F.; Magliozzi, M. L.; Majewski, S.; Torrioli, S.; Tsui, B. M. W.

2007-02-01

Our team is carrying on a systematic study devoted to the design of a SPECT detector with submillimeter resolution and adequate sensitivity (1 cps/kBq). Such system will be used for functional imaging of biological processes at molecular level in small animal. The system requirements have been defined by two relevant applications: study of atherosclerotic plaques characterization and stem cells diffusion and homing. In order to minimize costs and implementation time, the gamma detector will be based—as much as possible—on conventional components: scintillator crystal and position sensitive PhotoMultipliers read by individual channel electronics. A coded aperture collimator should be adapted to maximize the efficiency. The optimal selection of the detector components is investigated by systematic use of Monte-Carlo simulations (and laboratory validation tests); and finally preliminary results are presented and discussed here.

Imaging Potential Evaluation of Fab Derived from the Anti-EGFRvIII Monoclonal Antibody 4G1.

PubMed

Jing, Shen; He, Yujia; He, Yanqiong; Wang, Liang; Jia, Jianhua; Shan, Xiaomin; Liu, Shuang; Tang, Min; Peng, Zhiping; Liu, Xujie

2018-05-31

As one of the most crucial epidermal growth factor receptor (EGFR) variants, EGFRvIII can be detected in various tumors but rarely in normal tissues, making it an ideal target for prognosis, diagnosis or immune therapy. The recently developed anti-EGFRvIII monoclonal antibody (mAb), 4G1, has been validated as a promising molecular probe to detect EGFRvIII expression in tumors by single-photon emission computed tomography/computed tomography imaging. To overcome shortcomings associated with the whole antibody, including long-term retention, circulation and enhanced permeability and retention effects, the Fab fragment of 4G1 (Fab-4G1) was generated, labeled with 131 I and evaluated in vitro and in vivo to test its potential application in molecular imaging. Whole mAb 4G1 was first digested by immobilized ficin and then purified through a protein A column to generate the Fab fragment, Fab-4G1. Next, SDS-PAGE, Western blot, indirect fluorescence assay, flow cytometry and enzyme-linked immunosorbent assay were performed to verify molecular weight, specificity and affinity of Fab-4G1. Finally, biodistribution planar gamma imaging was performed by injection of 131 I-labeled Fab-4G1 into xenografted EGFRvIII-overexpressed tumors in nude mice. Parallel studies were also performed with intact 4G1. The molecular weight of Fab was determined to be 35-40 kDa by SDS-PAGE. In vitro tests confirmed both intact 4G1 and Fab-4G1 specifically bound EGFRvIII but not wild-type EGFR, and Fab-4G1 showed decreased affinity. Compared to 131 I-4G1, biodistribution studies showed lower tumor uptake of 131 I-Fab-4G1 at all time points, but much faster elimination in all normal organs. As for planar gamma imaging, 131 I-Fab-4G1 and 31 I-4G1 showed similar imaging effect at 2 h after injection of tracer, while 131 I-Fab-4G1 was eliminated more quickly with time, suggesting radiolabeled Fab-4G1 could be potentially used for imaging of EGFRvIII-positive tumors at early time points. Radiolabeled Fab-4G1 would be a promising nuclear probe for future clinical EGFRvIII tumor detection.

Evaluation of breast cancer using intravoxel incoherent motion (IVIM) histogram analysis: comparison with malignant status, histological subtype, and molecular prognostic factors.

PubMed

Cho, Gene Young; Moy, Linda; Kim, Sungheon G; Baete, Steven H; Moccaldi, Melanie; Babb, James S; Sodickson, Daniel K; Sigmund, Eric E

2016-08-01

To examine heterogeneous breast cancer through intravoxel incoherent motion (IVIM) histogram analysis. This HIPAA-compliant, IRB-approved retrospective study included 62 patients (age 48.44 ± 11.14 years, 50 malignant lesions and 12 benign) who underwent contrast-enhanced 3 T breast MRI and diffusion-weighted imaging. Apparent diffusion coefficient (ADC) and IVIM biomarkers of tissue diffusivity (Dt), perfusion fraction (fp), and pseudo-diffusivity (Dp) were calculated using voxel-based analysis for the whole lesion volume. Histogram analysis was performed to quantify tumour heterogeneity. Comparisons were made using Mann-Whitney tests between benign/malignant status, histological subtype, and molecular prognostic factor status while Spearman's rank correlation was used to characterize the association between imaging biomarkers and prognostic factor expression. The average values of the ADC and IVIM biomarkers, Dt and fp, showed significant differences between benign and malignant lesions. Additional significant differences were found in the histogram parameters among tumour subtypes and molecular prognostic factor status. IVIM histogram metrics, particularly fp and Dp, showed significant correlation with hormonal factor expression. Advanced diffusion imaging biomarkers show relationships with molecular prognostic factors and breast cancer malignancy. This analysis reveals novel diagnostic metrics that may explain some of the observed variability in treatment response among breast cancer patients. • Novel IVIM biomarkers characterize heterogeneous breast cancer. • Histogram analysis enables quantification of tumour heterogeneity. • IVIM biomarkers show relationships with breast cancer malignancy and molecular prognostic factors.

Near-infrared fluorescent nanoprobes for cancer molecular imaging: status and challenges

PubMed Central

He, Xiaoxiao; Gao, Jinhao; Gambhir, Sanjiv Sam; Cheng, Zhen

2010-01-01

Near-infrared fluorescence (NIRF) imaging promises to improve cancer imaging and management; advances in nanomaterials allow scientists to combine new nanoparticles with NIRF imaging techniques, thereby fulfilling this promise. Here, we present a synopsis of current developments in NIRF nanoprobes, their use in imaging small living subjects, their pharmacokinetics and toxicity and finally their integration into multimodal imaging strategies. We also discuss challenges impeding the clinical translation of NIRF nanoprobes for molecular imaging of cancer. Whereas utilization of most NIRF nanoprobes remains at a proof-of-principle stage, optimizing the impact of nanomedicine in cancer patient diagnosis and management will likely be realized through persistent interdisciplinary amalgamation of diverse research fields. PMID:20870460

Superparamagnetic iron oxide nanoparticles for MRI: contrast media pharmaceutical company R&D perspective.

PubMed

Corot, Claire; Warlin, David

2013-01-01

Superparamagnetic iron oxide (SPIO) nanoparticles are a relatively large class of contrast agents for magnetic resonance imaging. According to their biodistribution, distinct classes of SPIO nanoparticles have been investigated for clinical applications either as macrophage imaging agents or blood pool agents. Contrast agents which are pharmaceutics followed the same development rules as therapeutic drugs. Several drawbacks such as clinical development difficulties, organization of market access and imaging technological developments have limited the widespread use of these products. SPIO nanoparticles that are composed of thousands iron atoms providing large T2* effects are particularly suitable for theranostic. Stem cell migration and immune cell trafficking, as well as targeted SPIO nanoparticles for molecular imaging studies are mainly at the stage of proof of concept. A major economic challenge in the development of molecular imaging associated with a therapeutic treatment/procedure is to define innovative business models compatible with the needs of all players taking into account that theranostic solutions are promising to optimize resource allocation and ensure that expensive treatments are prescribed to responding patients. © 2013 Wiley Periodicals, Inc.

Regional tau deposition and subregion atrophy of medial temporal structures in early Alzheimer's disease: A combined positron emission tomography/magnetic resonance imaging study.

PubMed

Sone, Daichi; Imabayashi, Etsuko; Maikusa, Norihide; Okamura, Nobuyuki; Furumoto, Shozo; Kudo, Yukitsuka; Ogawa, Masayo; Takano, Harumasa; Yokoi, Yuma; Sakata, Masuhiro; Tsukamoto, Tadashi; Kato, Koichi; Matsuda, Hiroshi

2017-01-01

Molecular imaging and selective hippocampal subfield atrophy are a focus of recent Alzheimer's disease (AD) research. Here, we investigated correlations between molecular imaging and hippocampal subfields in early AD. We investigated 18 patients with early AD and 18 healthy control subjects using 11 C-Pittsburgh compound-B (PIB) positron emission tomography (PET) and 18 F-THK5351 PET and automatic segmentation of hippocampal subfields with high-resolution T2-weighted magnetic resonance imaging. The PET images were normalized and underwent voxelwise regression analysis with each subregion volumes using SPM12. As for 18 F-THK5351 PET, the bilateral perirhinal cortex volumes were significantly associated with the ipsilateral or bilateral temporal lobar uptakes, whereas hippocampal subfields showed no correlations. 11 C-PIB PET showed relatively broad negative correlation with the right cornu ammonis 3 volumes. Regional tau deposition was correlated with extrahippocampal subregional atrophy and not with hippocampal subfields, possibly reflecting different underlying mechanisms of atrophy in early AD. Amyloid might be associated with right cornu ammonis 3 atrophy.

Ionic channels in Langmuir-Blodgett films imaged by a scanning tunneling microscope.

PubMed Central

Kolomytkin, O V; Golubok, A O; Davydov, D N; Timofeev, V A; Vinogradova, S A; Tipisev SYa

1991-01-01

The molecular structure of channels formed by gramicidin A in a lipid membrane was imaged by a scanning tunneling microscope operating in air. The mono- and bimolecular films of lipid with gramicidin A were deposited onto a highly oriented pyrolitic graphite substrate by the Langmuir-Blodgett technique. It has been shown that under high concentration gramicidin A molecules can form in lipid films a quasi-regular, densely packed structure. Single gramicidin A molecules were imaged for the first time as well. The cavity of 0.4 +/- 0.05 nm in halfwidth was found on the scanning tunneling microscopy image of the gramicidin A molecule. The results of direct observation obtained by means of scanning tunneling microscope are in good agreement with the known molecular model of gramicidin A. It was shown that gramicidin A molecules can exist in a lipid monolayer as individual molecules or combined into clusters. The results demonstrate that scanning tunneling microscope can be used for high spatial resolution study of ionic channel structure. Images FIGURE 1 FIGURE 2 FIGURE 4 FIGURE 5 PMID:1712239

A multimodal imaging platform with integrated simultaneous photoacoustic microscopy, optical coherence tomography, optical Doppler tomography and fluorescence microscopy

NASA Astrophysics Data System (ADS)

Dadkhah, Arash; Zhou, Jun; Yeasmin, Nusrat; Jiao, Shuliang

2018-02-01

Various optical imaging modalities with different optical contrast mechanisms have been developed over the past years. Although most of these imaging techniques are being used in many biomedical applications and researches, integration of these techniques will allow researchers to reach the full potential of these technologies. Nevertheless, combining different imaging techniques is always challenging due to the difference in optical and hardware requirements for different imaging systems. Here, we developed a multimodal optical imaging system with the capability of providing comprehensive structural, functional and molecular information of living tissue in micrometer scale. This imaging system integrates photoacoustic microscopy (PAM), optical coherence tomography (OCT), optical Doppler tomography (ODT) and fluorescence microscopy in one platform. Optical-resolution PAM (OR-PAM) provides absorption-based imaging of biological tissues. Spectral domain OCT is able to provide structural information based on the scattering property of biological sample with no need for exogenous contrast agents. In addition, ODT is a functional extension of OCT with the capability of measurement and visualization of blood flow based on the Doppler effect. Fluorescence microscopy allows to reveal molecular information of biological tissue using autofluoresce or exogenous fluorophores. In-vivo as well as ex-vivo imaging studies demonstrated the capability of our multimodal imaging system to provide comprehensive microscopic information on biological tissues. Integrating all the aforementioned imaging modalities for simultaneous multimodal imaging has promising potential for preclinical research and clinical practice in the near future.

Imaging Molecular Signatures of Breast Cancer With X-ray Activated Nano-Phosphors

DTIC Science & Technology

2011-09-01

high resolution with a decrease in X-ray dose to healthy tissue. For the first-year training goals, this grant has provided for extensive study in...europium (red) were studied . The light emission was imaged in a clinical X-ray scanner with a cooled CCD camera and a spectrophotometer; dose...Indeed, in a preliminary study , these phosphor were targeted to the Folate receptor (commonly expressed in breast cancer), and uptaken by live cells

The Importance of Biopsy in the Era of Molecular Medicine.

PubMed

Ziv, Etay; Durack, Jeremy C; Solomon, Stephen B

Recent advances in the molecular characterization of cancers have triggered interest in developing a new taxonomy of disease in oncology with the goal of using the molecular profile of a patient's tumor to predict response to treatment. Image-guided needle biopsy is central to this "precision medicine" effort. In this review, we first discuss the current role of biopsy in relation to clinical examples of molecular medicine. We then outline important bottlenecks to the advancement of precision medicine and highlight the potential role of image-guided biopsy to address these challenges.

Label-free in vivo imaging of Drosophila melanogaster by multiphoton microscopy

NASA Astrophysics Data System (ADS)

Lin, Chiao-Ying; Hovhannisyan, Vladimir; Wu, June-Tai; Lin, Sung-Jan; Lin, Chii-Wann; Chen, Jyh-Horng; Dong, Chen-Yuan

2008-02-01

The fruit fly Drosophila melanogaster is one of the most valuable organisms in genetic and developmental biology studies. Drosophila is a small organism with a short life cycle, and is inexpensive and easy to maintain. The entire genome of Drosophila has recently been sequenced (cite the reference). These advantages make fruit fly an attractive model organism for biomedical researches. Unlike humans, Drosophila can be subjected to genetic manipulation with relative ease. Originally, Drosophila was mostly used in classical genetics studies. In the model era of molecular biology, the fruit fly has become a model organ for developmental biology researches. In the past, numerous molecularly modified mutants with well defined genetic defects affecting different aspects of the developmental processes have been identified and studied. However, traditionally, the developmental defects of the mutant flies are mostly examined in isolated fixed tissues which preclude the observation of the dynamic interaction of the different cell types and the extracellular matrix. Therefore, the ability to image different organelles of the fruit fly without extrinsic labeling is invaluable for Drosophila biology. In this work, we successfully acquire in vivo images of both developing muscles and axons of motor neurons in the three larval stages by using the minimially invasive imaging modality of multiphoton (SHG) microscopy. We found that while SHG imaging is useful in revealing the muscular architecture of the developing larva, it is the autofluorescence signal that allows label-free imaging of various organelles to be achieved. Our results demonstrate that multiphoton imaging is a powerful technique for investigation the development of Drosophila.

Surface enhanced Raman scattering on Tardigrada--towards monitoring and imaging molecular structures in live cryptobiotic organisms.

PubMed

Kneipp, Harald; Møbjerg, Nadja; Jørgensen, Aslak; Bohr, Henrik G; Hélix-Nielsen, Claus; Kneipp, Janina; Kneipp, Katrin

2013-10-01

Tardigrades are microscopic metazoans which are able to survive extreme physical and chemical conditions by entering a stress tolerant state called cryptobiosis. At present, the molecular mechanisms behind cryptobiosis are still poorly understood. We show that surface enhanced Raman scattering supported by plasmonic gold nanoparticles can measure molecular constituents and their local distribution in live tardigrades. Surface enhanced Raman signatures allow to differentiate between two species and indicate molecular structural differences between tardigrades in water and in a dry state. This opens new avenues for exploring cryptobiosis by studying molecular changes in live cryptobiotic organisms. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Molecular Origin of Color Variation in Firefly (Beetle) Bioluminescence: A Chemical Basis for Biological Imaging.

PubMed

Hirano, Takashi

2016-01-01

Firefly shows bioluminescence by "luciferin-luciferase" (L-L) reaction using luciferin, luciferase, ATP and O2. The chemical photon generation by an enzymatic reaction is widely utilized for analytical methods including biological imaging in the life science fields. To expand photondetecting analyses with firefly bioluminescence, it is important for users to understand the chemical basis of the L-L reaction. In particular, the emission color variation of the L-L reaction is one of the distinguishing characteristics for multicolor luciferase assay and in vivo imaging. From the viewpoint of fundamental chemistry, this review explains the recent progress in the studies on the molecular mechanism of emission color variation after showing the outline of the reaction mechanism of the whole L-L reaction. On the basis of the mechanism, the progresses in organic synthesis of luciferin analogs modulating their emission colors are also presented to support further developments of red/near infrared in vivo biological imaging utility of firefly bioluminescence.

Residualization Rates of Near Infrared Dyes for the Rational Design of Molecular Imaging Agents

PubMed Central

Cilliers, Cornelius; Liao, Jianshan; Atangcho, Lydia; Thurber, Greg M.

2016-01-01

Purpose Near infrared (NIR) fluorescence imaging is widely used for tracking antibodies and biomolecules in vivo. Clinical and preclinical applications include intraoperative imaging, tracking therapeutics, and fluorescent labeling as a surrogate for subsequent radiolabeling. Despite their extensive use, one of the fundamental properties of NIR dyes, the residualization rate within cells following internalization, has not been systematically studied. This rate is required for the rational design of probes and proper interpretation of in vivo results. Procedures In this brief report, we measure the cellular residualization rate of eight commonly used dyes encompassing three core structures (cyanine, BODIPY, and oxazine/thiazine/carbopyronin). Results We identify residualizing (half-life > 24 hrs) and non-residualizing dyes (half-life < 24 hrs) in both the far red (~650-680 nm) and near infrared (~740-800 nm) regions. Conclusions This data will allow researchers to independently and rationally select the wavelength and residualizing nature of dyes for molecular imaging agent design. PMID:25869081

Residualization Rates of Near-Infrared Dyes for the Rational Design of Molecular Imaging Agents.

PubMed

Cilliers, Cornelius; Liao, Jianshan; Atangcho, Lydia; Thurber, Greg M

2015-12-01

Near-infrared (NIR) fluorescence imaging is widely used for tracking antibodies and biomolecules in vivo. Clinical and preclinical applications include intraoperative imaging, tracking therapeutics, and fluorescent labeling as a surrogate for subsequent radiolabeling. Despite their extensive use, one of the fundamental properties of NIR dyes, the residualization rate within cells following internalization, has not been systematically studied. This rate is required for the rational design of probes and proper interpretation of in vivo results. In this brief report, we measure the cellular residualization rate of eight commonly used dyes encompassing three core structures (cyanine, boron-dipyrromethene (BODIPY), and oxazine/thiazine/carbopyronin). We identify residualizing (half-life >24 h) and non-residualizing (half-life <24 h) dyes in both the far-red (~650-680 nm) and near-infrared (~740-800 nm) regions. This data will allow researchers to independently and rationally select the wavelength and residualizing nature of dyes for molecular imaging agent design.

[Molecular imaging of tumor blood vessels].

PubMed

Tilki, D; Singer, B; Seitz, M; Stief, C G; Ergün, S

2007-09-01

In the past three decades many efforts have been undertaken to understand the mechanisms of tumor angiogenesis. The introduction of the anti-angiogenic drugs in tumor therapy during the last few years necessitates the establishment of new techniques enabling molecular imaging of vascular remodeling. Tumor imaging by X-ray, CT, MRI and ultrasound has to be improved by coupling with molecular markers targeting the tumor vessels. The determination of tumor size as commonly used is not appropriate since the extended necrosis under anti-angiogenic therapy does not result in a reduction of tumor diameter. But remodeling of the tumor vessels under anti-angiogenic therapy obviously occurs at an early stage and seems to be a convincing parameter for tumor imaging. Despite the enormous progress in this field during the last few years the resolution is still not high enough to evaluate the remodeling of the microtumor vessels. Thus, new imaging approaches are needed to overcome this issue.

Molecular intravascular imaging approaches for atherosclerosis.

PubMed

Press, Marcella Calfon; Jaffer, Farouc A

2014-10-01

Coronary artery disease (CAD) is an inflammatory process that results in buildup of atherosclerosis, typically lipid-rich plaque in the arterial wall. Progressive narrowing of the vessel wall and subsequent plaque rupture can lead to myocardial infarction and death. Recent advances in intravascular fluorescence imaging techniques have provided exciting coronary artery-targeted platforms to further characterize the molecular changes that occur within the vascular wall as a result of atherosclerosis and following coronary stent-induced vascular injury. This review will summarize exciting recent developments in catheter-based imaging of coronary arterial-sized vessels; focusing on two-dimensional near-infrared fluorescence imaging (NIRF) molecular imaging technology as an approach to specifically identify inflammation and fibrin directly within coronary artery-sized vessels. Intravascular NIRF is anticipated to provide new insights into the in vivo biology underlying high-risk plaques, as well as high-risks stents prone to stent restenosis or stent thrombosis.

Recent Advances in Molecular, Multimodal and Theranostic Ultrasound Imaging

PubMed Central

Kiessling, Fabian; Fokong, Stanley; Bzyl, Jessica; Lederle, Wiltrud; Palmowski, Moritz; Lammers, Twan

2014-01-01

Ultrasound (US) imaging is an exquisite tool for the non-invasive and real-time diagnosis of many different diseases. In this context, US contrast agents can improve lesion delineation, characterization and therapy response evaluation. US contrast agents are usually micrometer-sized gas bubbles, stabilized with soft or hard shells. By conjugating antibodies to the microbubble (MB) surface, and by incorporating diagnostic agents, drugs or nucleic acids into or onto the MB shell, molecular, multimodal and theranostic MB can be generated. We here summarize recent advances in molecular, multimodal and theranostic US imaging, and introduce concepts how such advanced MB can be generated, applied and imaged. Examples are given for their use to image and treat oncological, cardiovascular and neurological diseases. Furthermore, we discuss for which therapeutic entities incorporation into (or conjugation to) MB is meaningful, and how US-mediated MB destruction can increase their extravasation, penetration, internalization and efficacy. PMID:24316070

Multiplexed Five-Color Molecular Imaging of Cancer Cells and Tumor Tissues with Carbon Nanotube Raman Tags in the Near-Infrared

PubMed Central

Liu, Zhuang; Tabakman, Scott; Sherlock, Sarah; Li, Xiaolin; Chen, Zhuo; Jiang, Kaili; Fan, Shoushan; Dai, Hongjie

2011-01-01

Single-walled carbon nanotubes (SWNTs) with five different C13/C12 isotope compositions and well-separated Raman peaks have been synthesized and conjugated to five targeting ligands in order to impart molecular specificity. Multiplexed Raman imaging of live cells has been carried out by highly specific staining of cells with a five-color mixture of SWNTs. Ex vivo multiplexed Raman imaging of tumor samples uncovers a surprising up-regulation of epidermal growth factor receptor (EGFR) on LS174T colon cancer cells from cell culture to in vivo tumor growth. This is the first time five-color multiplexed molecular imaging has been performed in the near-infrared (NIR) region under a single laser excitation. Near zero interfering background of imaging is achieved due to the sharp Raman peaks unique to nanotubes over the low, smooth autofluorescence background of biological species. PMID:21442006

Advances in Magnetic Resonance Imaging Contrast Agents for Biomarker Detection

PubMed Central

Sinharay, Sanhita; Pagel, Mark D.

2016-01-01

Recent advances in magnetic resonance imaging (MRI) contrast agents have provided new capabilities for biomarker detection through molecular imaging. MRI contrast agents based on the T2 exchange mechanism have more recently expanded the armamentarium of agents for molecular imaging. Compared with T1 and T2* agents, T2 exchange agents have a slower chemical exchange rate, which improves the ability to design these MRI contrast agents with greater specificity for detecting the intended biomarker. MRI contrast agents that are detected through chemical exchange saturation transfer (CEST) have even slower chemical exchange rates. Another emerging class of MRI contrast agents uses hyperpolarized 13C to detect the agent with outstanding sensitivity. These hyperpolarized 13C agents can be used to track metabolism and monitor characteristics of the tissue microenvironment. Together, these various MRI contrast agents provide excellent opportunities to develop molecular imaging for biomarker detection. PMID:27049630

Systems Biology-Driven Hypotheses Tested In Vivo: The Need to Advancing Molecular Imaging Tools.

PubMed

Verma, Garima; Palombo, Alessandro; Grigioni, Mauro; La Monaca, Morena; D'Avenio, Giuseppe

2018-01-01

Processing and interpretation of biological images may provide invaluable insights on complex, living systems because images capture the overall dynamics as a "whole." Therefore, "extraction" of key, quantitative morphological parameters could be, at least in principle, helpful in building a reliable systems biology approach in understanding living objects. Molecular imaging tools for system biology models have attained widespread usage in modern experimental laboratories. Here, we provide an overview on advances in the computational technology and different instrumentations focused on molecular image processing and analysis. Quantitative data analysis through various open source software and algorithmic protocols will provide a novel approach for modeling the experimental research program. Besides this, we also highlight the predictable future trends regarding methods for automatically analyzing biological data. Such tools will be very useful to understand the detailed biological and mathematical expressions under in-silico system biology processes with modeling properties.

Mesoscale imaging with cryo-light and X-rays: Larger than molecular machines, smaller than a cell: Mesoscale imaging with cryo-light and X-rays

DOE PAGES

Ekman, Axel A.; Chen, Jian-Hua; Guo, Jessica; ...

2016-11-14

In the context of cell biology, the term mesoscale describes length scales ranging from that of an individual cell, down to the size of the molecular machines. In this spatial regime, small building blocks self-organise to form large, functional structures. A comprehensive set of rules governing mesoscale self-organisation has not been established, making the prediction of many cell behaviours difficult, if not impossible. Our knowledge of mesoscale biology comes from experimental data, in particular, imaging. Here, we explore the application of soft X-ray tomography (SXT) to imaging the mesoscale, and describe the structural insights this technology can generate. We alsomore » discuss how SXT imaging is complemented by the addition of correlative fluorescence data measured from the same cell. This combination of two discrete imaging modalities produces a 3D view of the cell that blends high-resolution structural information with precise molecular localisation data.« less

Recent Development of Inorganic Nanoparticles for Biomedical Imaging

PubMed Central

2018-01-01

Inorganic nanoparticle-based biomedical imaging probes have been studied extensively as a potential alternative to conventional molecular imaging probes. Not only can they provide better imaging performance but they can also offer greater versatility of multimodal, stimuli-responsive, and targeted imaging. However, inorganic nanoparticle-based probes are still far from practical use in clinics due to safety concerns and less-optimized efficiency. In this context, it would be valuable to look over the underlying issues. This outlook highlights the recent advances in the development of inorganic nanoparticle-based probes for MRI, CT, and anti-Stokes shift-based optical imaging. Various issues and possibilities regarding the construction of imaging probes are discussed, and future research directions are suggested. PMID:29632878

Raman Imaging of Plant Cell Walls in Sections of Cucumis sativus

PubMed Central

Zeise, Ingrid; Heiner, Zsuzsanna; Holz, Sabine; Joester, Maike; Büttner, Carmen

2018-01-01

Raman microspectra combine information on chemical composition of plant tissues with spatial information. The contributions from the building blocks of the cell walls in the Raman spectra of plant tissues can vary in the microscopic sub-structures of the tissue. Here, we discuss the analysis of 55 Raman maps of root, stem, and leaf tissues of Cucumis sativus, using different spectral contributions from cellulose and lignin in both univariate and multivariate imaging methods. Imaging based on hierarchical cluster analysis (HCA) and principal component analysis (PCA) indicates different substructures in the xylem cell walls of the different tissues. Using specific signals from the cell wall spectra, analysis of the whole set of different tissue sections based on the Raman images reveals differences in xylem tissue morphology. Due to the specifics of excitation of the Raman spectra in the visible wavelength range (532 nm), which is, e.g., in resonance with carotenoid species, effects of photobleaching and the possibility of exploiting depletion difference spectra for molecular characterization in Raman imaging of plants are discussed. The reported results provide both, specific information on the molecular composition of cucumber tissue Raman spectra, and general directions for future imaging studies in plant tissues. PMID:29370089

Raman Imaging of Plant Cell Walls in Sections of Cucumis sativus.

PubMed

Zeise, Ingrid; Heiner, Zsuzsanna; Holz, Sabine; Joester, Maike; Büttner, Carmen; Kneipp, Janina

2018-01-25

Raman microspectra combine information on chemical composition of plant tissues with spatial information. The contributions from the building blocks of the cell walls in the Raman spectra of plant tissues can vary in the microscopic sub-structures of the tissue. Here, we discuss the analysis of 55 Raman maps of root, stem, and leaf tissues of Cucumis sativus , using different spectral contributions from cellulose and lignin in both univariate and multivariate imaging methods. Imaging based on hierarchical cluster analysis (HCA) and principal component analysis (PCA) indicates different substructures in the xylem cell walls of the different tissues. Using specific signals from the cell wall spectra, analysis of the whole set of different tissue sections based on the Raman images reveals differences in xylem tissue morphology. Due to the specifics of excitation of the Raman spectra in the visible wavelength range (532 nm), which is, e.g., in resonance with carotenoid species, effects of photobleaching and the possibility of exploiting depletion difference spectra for molecular characterization in Raman imaging of plants are discussed. The reported results provide both, specific information on the molecular composition of cucumber tissue Raman spectra, and general directions for future imaging studies in plant tissues.

All-near-infrared multiphoton microscopy interrogates intact tissues at deeper imaging depths than conventional single- and two-photon near-infrared excitation microscopes

PubMed Central

Sarder, Pinaki; Yazdanfar, Siavash; Akers, Walter J.; Tang, Rui; Sudlow, Gail P.; Egbulefu, Christopher

2013-01-01

Abstract. The era of molecular medicine has ushered in the development of microscopic methods that can report molecular processes in thick tissues with high spatial resolution. A commonality in deep-tissue microscopy is the use of near-infrared (NIR) lasers with single- or multiphoton excitations. However, the relationship between different NIR excitation microscopic techniques and the imaging depths in tissue has not been established. We compared such depth limits for three NIR excitation techniques: NIR single-photon confocal microscopy (NIR SPCM), NIR multiphoton excitation with visible detection (NIR/VIS MPM), and all-NIR multiphoton excitation with NIR detection (NIR/NIR MPM). Homologous cyanine dyes provided the fluorescence. Intact kidneys were harvested after administration of kidney-clearing cyanine dyes in mice. NIR SPCM and NIR/VIS MPM achieved similar maximum imaging depth of ∼100  μm. The NIR/NIR MPM enabled greater than fivefold imaging depth (>500  μm) using the harvested kidneys. Although the NIR/NIR MPM used 1550-nm excitation where water absorption is relatively high, cell viability and histology studies demonstrate that the laser did not induce photothermal damage at the low laser powers used for the kidney imaging. This study provides guidance on the imaging depth capabilities of NIR excitation-based microscopic techniques and reveals the potential to multiplex information using these platforms. PMID:24150231

Fluorescence background subtraction technique for hybrid fluorescence molecular tomography/x-ray computed tomography imaging of a mouse model of early stage lung cancer.

PubMed

Ale, Angelique; Ermolayev, Vladimir; Deliolanis, Nikolaos C; Ntziachristos, Vasilis

2013-05-01

The ability to visualize early stage lung cancer is important in the study of biomarkers and targeting agents that could lead to earlier diagnosis. The recent development of hybrid free-space 360-deg fluorescence molecular tomography (FMT) and x-ray computed tomography (XCT) imaging yields a superior optical imaging modality for three-dimensional small animal fluorescence imaging over stand-alone optical systems. Imaging accuracy was improved by using XCT information in the fluorescence reconstruction method. Despite this progress, the detection sensitivity of targeted fluorescence agents remains limited by nonspecific background accumulation of the fluorochrome employed, which complicates early detection of murine cancers. Therefore we examine whether x-ray CT information and bulk fluorescence detection can be combined to increase detection sensitivity. Correspondingly, we research the performance of a data-driven fluorescence background estimator employed for subtraction of background fluorescence from acquisition data. Using mice containing known fluorochromes ex vivo, we demonstrate the reduction of background signals from reconstructed images and sensitivity improvements. Finally, by applying the method to in vivo data from K-ras transgenic mice developing lung cancer, we find small tumors at an early stage compared with reconstructions performed using raw data. We conclude with the benefits of employing fluorescence subtraction in hybrid FMT-XCT for early detection studies.

A Partnership Training Program: Studying Targeted Drug Delivery Using Nanoparticles in Breast Cancer Diagnosis and Therapy

DTIC Science & Technology

2012-10-01

studying potential toxicity of nanoparticles. We have shown that A-dmDT(390)-scfbDb(PSMA), a single chain Fv fragments of antibody with diphtheria toxin...smart’ agents activated by specific enzymes , or based on the expression of detectable reporters [3, 4]. These molecular imaging capabilities, in...understanding of these interactions will greatly assist in the design of smart drugs and targeted CAs delivery, with great potential for molecular-based

Near-infrared fluorescence molecular imaging of amyloid beta species and monitoring therapy in animal models of Alzheimer’s disease

PubMed Central

Zhang, Xueli; Tian, Yanli; Zhang, Can; Tian, Xiaoyu; Ross, Alana W.; Moir, Robert D.; Sun, Hongbin; Tanzi, Rudolph E.; Moore, Anna; Ran, Chongzhao

2015-01-01

Near-infrared fluorescence (NIRF) molecular imaging has been widely applied to monitoring therapy of cancer and other diseases in preclinical studies; however, this technology has not been applied successfully to monitoring therapy for Alzheimer’s disease (AD). Although several NIRF probes for detecting amyloid beta (Aβ) species of AD have been reported, none of these probes has been used to monitor changes of Aβs during therapy. In this article, we demonstrated that CRANAD-3, a curcumin analog, is capable of detecting both soluble and insoluble Aβ species. In vivo imaging showed that the NIRF signal of CRANAD-3 from 4-mo-old transgenic AD (APP/PS1) mice was 2.29-fold higher than that from age-matched wild-type mice, indicating that CRANAD-3 is capable of detecting early molecular pathology. To verify the feasibility of CRANAD-3 for monitoring therapy, we first used the fast Aβ-lowering drug LY2811376, a well-characterized beta-amyloid cleaving enzyme-1 inhibitor, to treat APP/PS1 mice. Imaging data suggested that CRANAD-3 could monitor the decrease in Aβs after drug treatment. To validate the imaging capacity of CRANAD-3 further, we used it to monitor the therapeutic effect of CRANAD-17, a curcumin analog for inhibition of Aβ cross-linking. The imaging data indicated that the fluorescence signal in the CRANAD-17–treated group was significantly lower than that in the control group, and the result correlated with ELISA analysis of brain extraction and Aβ plaque counting. It was the first time, to our knowledge, that NIRF was used to monitor AD therapy, and we believe that our imaging technology has the potential to have a high impact on AD drug development. PMID:26199414

Molecular imaging of human tumor cells that naturally overexpress type 2 cannabinoid receptors using a quinolone-based near-infrared fluorescent probe

NASA Astrophysics Data System (ADS)

Wu, Zhiyuan; Shao, Pin; Zhang, Shaojuan; Ling, Xiaoxi; Bai, Mingfeng

2014-07-01

Cannabinoid CB2 receptors (CB2R) hold promise as therapeutic targets for treating diverse diseases, such as cancers, neurodegenerative diseases, pain, inflammation, osteoporosis, psychiatric disorders, addiction, and immune disorders. However, the fundamental role of CBR in the regulation of diseases remains unclear, largely due to a lack of reliable imaging tools for the receptors. The goal of this study was to develop a CBR-targeted molecular imaging probe and evaluate the specificity of the probe using human tumor cells that naturally overexpress CBR. To synthesize the CBR-targeted probe (NIR760-Q), a conjugable CBR ligand based on the quinolone structure was first prepared, followed by bioconjugation with a near-infrared (NIR) fluorescent dye, NIR760. In vitro fluorescence imaging and competitive binding studies showed higher uptake of NIR760-Q than free NIR760 dye in Jurkat human acute T-lymphoblastic leukemia cells. In addition, the high uptake of NIR760-Q was significantly inhibited by the blocking agent, 4-quinolone-3-carboxamide, indicating specific binding of NIR760-Q to the target receptors. These results indicate that the NIR760-Q has potential in diagnostic imaging of CBR positive cancers and elucidating the role of CBR in the regulation of disease progression.

A high quantum yield molecule-protein complex fluorophore for near-infrared II imaging

PubMed Central

Antaris, Alexander L.; Chen, Hao; Diao, Shuo; Ma, Zhuoran; Zhang, Zhe; Zhu, Shoujun; Wang, Joy; Lozano, Alexander X.; Fan, Quli; Chew, Leila; Zhu, Mark; Cheng, Kai; Hong, Xuechuan; Dai, Hongjie; Cheng, Zhen

2017-01-01

Fluorescence imaging in the second near-infrared window (NIR-II) allows visualization of deep anatomical features with an unprecedented degree of clarity. NIR-II fluorophores draw from a broad spectrum of materials spanning semiconducting nanomaterials to organic molecular dyes, yet unfortunately all water-soluble organic molecules with >1,000 nm emission suffer from low quantum yields that have limited temporal resolution and penetration depth. Here, we report tailoring the supramolecular assemblies of protein complexes with a sulfonated NIR-II organic dye (CH-4T) to produce a brilliant 110-fold increase in fluorescence, resulting in the highest quantum yield molecular fluorophore thus far. The bright molecular complex allowed for the fastest video-rate imaging in the second NIR window with ∼50-fold reduced exposure times at a fast 50 frames-per-second (FPS) capable of resolving mouse cardiac cycles. In addition, we demonstrate that the NIR-II molecular complexes are superior to clinically approved ICG for lymph node imaging deep within the mouse body. PMID:28524850

A high quantum yield molecule-protein complex fluorophore for near-infrared II imaging

DOE Office of Scientific and Technical Information (OSTI.GOV)

Antaris, Alexander L.; Chen, Hao; Diao, Shuo

Fluorescence imaging in the second near-infrared window (NIR-II) allows visualization of deep anatomical features with an unprecedented degree of clarity. NIR-II fluorophores draw from a broad spectrum of materials spanning semiconducting nanomaterials to organic molecular dyes, yet unfortunately all water-soluble organic molecules with 41,000 nm emission suffer from low quantum yields that have limited temporal resolution and penetration depth. We report tailoring the supramolecular assemblies of protein complexes with a sulfonated NIR-II organic dye (CH-4T) to produce a brilliant 110-fold increase in fluorescence, resulting in the highest quantum yield molecular fluorophore thus far. The bright molecular complex allowed for themore » fastest video-rate imaging in the second NIR window with B50-fold reduced exposure times at a fast 50 frames-per-second (FPS) capable of resolving mouse cardiac cycles. Additionally, we demonstrate that the NIR-II molecular complexes are superior to clinically approved ICG for lymph node imaging deep within the mouse body.« less

A high quantum yield molecule-protein complex fluorophore for near-infrared II imaging

DOE PAGES

Antaris, Alexander L.; Chen, Hao; Diao, Shuo; ...

2017-05-19

Fluorescence imaging in the second near-infrared window (NIR-II) allows visualization of deep anatomical features with an unprecedented degree of clarity. NIR-II fluorophores draw from a broad spectrum of materials spanning semiconducting nanomaterials to organic molecular dyes, yet unfortunately all water-soluble organic molecules with 41,000 nm emission suffer from low quantum yields that have limited temporal resolution and penetration depth. We report tailoring the supramolecular assemblies of protein complexes with a sulfonated NIR-II organic dye (CH-4T) to produce a brilliant 110-fold increase in fluorescence, resulting in the highest quantum yield molecular fluorophore thus far. The bright molecular complex allowed for themore » fastest video-rate imaging in the second NIR window with B50-fold reduced exposure times at a fast 50 frames-per-second (FPS) capable of resolving mouse cardiac cycles. Additionally, we demonstrate that the NIR-II molecular complexes are superior to clinically approved ICG for lymph node imaging deep within the mouse body.« less

Towards a high sensitivity small animal PET system based on CZT detectors (Conference Presentation)

NASA Astrophysics Data System (ADS)

Abbaszadeh, Shiva; Levin, Craig

2017-03-01

Small animal positron emission tomography (PET) is a biological imaging technology that allows non-invasive interrogation of internal molecular and cellular processes and mechanisms of disease. New PET molecular probes with high specificity are under development to target, detect, visualize, and quantify subtle molecular and cellular processes associated with cancer, heart disease, and neurological disorders. However, the limited uptake of these targeted probes leads to significant reduction in signal. There is a need to advance the performance of small animal PET system technology to reach its full potential for molecular imaging. Our goal is to assemble a small animal PET system based on CZT detectors and to explore methods to enhance its photon sensitivity. In this work, we reconstruct an image from a phantom using a two-panel subsystem consisting of six CZT crystals in each panel. For image reconstruction, coincidence events with energy between 450 and 570 keV were included. We are developing an algorithm to improve sensitivity of the system by including multiple interaction events.

Molecular imaging probe development: a chemistry perspective

PubMed Central

Nolting, Donald D; Nickels, Michael L; Guo, Ning; Pham, Wellington

2012-01-01

Molecular imaging is an attractive modality that has been widely employed in many aspects of biomedical research; especially those aimed at the early detection of diseases such as cancer, inflammation and neurodegenerative disorders. The field emerged in response to a new research paradigm in healthcare that seeks to integrate detection capabilities for the prediction and prevention of diseases. This approach made a distinct impact in biomedical research as it enabled researchers to leverage the capabilities of molecular imaging probes to visualize a targeted molecular event non-invasively, repeatedly and continuously in a living system. In addition, since such probes are inherently compact, robust, and amenable to high-throughput production, these probes could potentially facilitate screening of preclinical drug discovery, therapeutic assessment and validation of disease biomarkers. They could also be useful in drug discovery and safety evaluations. In this review, major trends in the chemical synthesis and development of positron emission tomography (PET), optical and magnetic resonance imaging (MRI) probes are discussed. PMID:22943038

Tc-99m Glu-Cys-Gly-His-Gly-Lys (ECG-HGK), a novel Tc-99m labeled hexapeptide for molecular tumor imaging.

PubMed

Kim, Dae-Weung; Kim, Myoung Hyoun; Kim, Chang Guhn

2016-03-01

Domain 5 of kinin-free high molecular weight kininogen inhibits the adhesion of many tumor cell lines, and it has been reported that the histidine-glycine-lysine (HGK)-rich region might be responsible for inhibition of cell adhesion. The authors developed HGK-containing hexapeptide, glutamic acid-cysteine-glycine (ECG)-HGK, and evaluated the utility of Tc-99m ECG-HGK for tumor imaging. Hexapeptide, ECG-HGK was synthesized using Fmoc solid-phase peptide synthesis. Radiolabeling efficiency was evaluated. The uptake of Tc-99m ECG-HGK within HT-1080 cells was evaluated in vitro. In HT-1080 tumor-bearing mice, gamma imaging and biodistribution studies were performed. The complexes Tc-99m ECG-HGK was prepared in high yield. The uptake of Tc-99m ECG-HGK within the HT-1080 tumor cells had been demonstrated by in vitro studies. The gamma camera imaging in the murine model showed that Tc-99m ECG-HGK was accumulated substantially in the HT-1080 tumor (tumor-to-muscle ratio = 5.7 ± 1.4 at 4 h), and the tumoral uptake was blocked by the co-injection of excess HGK (tumor-to-muscle ratio = 2.8 ± 0.6 at 4 h). In the present study, Tc-99m ECG-HGK was developed as a new tumor imaging agents. Our in vitro and in vivo studies revealed specific function of Tc-99m ECG-HGK for tumor imaging. Copyright © 2016 John Wiley & Sons, Ltd.

Proton magnetic resonance spectroscopy imaging in the study of human brain cancer.

PubMed

Martínez-Bisbal, M C; Celda, B

2009-12-01

Magnetic resonance spectroscopic imaging (MRSI) is a non-invasive imaging technique that provides metabolic information on brain tumor. This biochemical information can be processed and presented as density maps of several metabolites, among them N-acetylaspartate (marker of neuronal viability), choline (marker of membrane turnover), creatine (related to the energy state of the cells), myo-Inositol (exclusively found in astrocytes), lipids and lactate (observed in necrosis and other pathological processes) which mean relevant information in the context of brain tumors. Thus, this technique is a multiparametrical molecular imaging method that can complete the magnetic resonance imaging (MRI) study enabling the detection of biochemical patterns of different features and aspects of brain tumors. In this article, the role of MRSI as a molecular imaging technique to provide biochemical information on human brain tumors is reviewed. The most frequent questions and situations in the study of human brain tumors in clinical settings will be considered, as well as the distinction of neoplastic lesions from non neoplastic, the tumor type identification, the study of heterogeneity and infiltration of normal appearing white matter and the therapy following with detection of side effects. The great amount of data in MRSI acquisition compared to the single voxel techniques requires the use of automated methods of quantification, but the possibility to obtain self-reference in the non-affected areas allows different strategies for data handling and interpretation, as presented in the literature. The combination of MRSI with other physiological MRI techniques and positron emission tomography is also included in this review.

MRI-guided fluorescence tomography of the breast: a phantom study

NASA Astrophysics Data System (ADS)

Davis, Scott C.; Pogue, Brian W.; Dehghani, Hamid; Paulsen, Keith D.

2009-02-01

Tissue phantoms simulating the human breast were used to demonstrate the imaging capabilities of an MRI-coupled fluorescence molecular tomography (FMT) imaging system. Specifically, phantoms with low tumor-to-normal drug contrast and complex internal structure were imaged with the MR-coupled FMT system. Images of indocyanine green (ICG) fluorescence yield were recovered using a diffusion model-based approach capable of estimating the distribution of fluorescence activity in a tissue volume from tissue-boundary measurements of transmitted light. Tissue structural information, which can be determined from standard T1 and T2 MR images, was used to guide the recovery of fluorescence activity. The study revealed that this spatial guidance is critical for recovering images of fluorescence yield in tissue with low tumor-to-normal drug contrast.